CA2776471A1 - Surfactant-free, water-free, foamable compositions and breakable foams and their uses - Google Patents
Surfactant-free, water-free, foamable compositions and breakable foams and their uses Download PDFInfo
- Publication number
- CA2776471A1 CA2776471A1 CA2776471A CA2776471A CA2776471A1 CA 2776471 A1 CA2776471 A1 CA 2776471A1 CA 2776471 A CA2776471 A CA 2776471A CA 2776471 A CA2776471 A CA 2776471A CA 2776471 A1 CA2776471 A1 CA 2776471A1
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- Prior art keywords
- oil
- agent
- ppg
- composition
- ether
- Prior art date
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/10—Washing or bathing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/30—Characterized by the absence of a particular group of ingredients
- A61K2800/31—Anhydrous
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/30—Characterized by the absence of a particular group of ingredients
- A61K2800/33—Free of surfactant
Abstract
A substantially surface active agent-free and foam adjuvant- free composition which includes a hydrophobic solvent, a wax and a propellant. A substantially surface active agent-free and foam adjuvant- free composition, further comprising, a tetracycline antibiotic, or one or more other active agents. A method of treatment, using a substantially surface active agent- free and substantially foam adjuvant-free composition.
Description
SURFACTANT-FREE, WATER-FREE, FOAMABLE COMPOSITIONS AND
BREAKABLE FOAMS AND THEIR USES
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority under 35 U.S.C.
119(e) to United States Provisional Application No. 61/248,144 filed October 2, 2009 and entitled "Surfactant-Free Water-Free Foamable Compositions, Breakable Foams and Their Uses; United States Provisional Application No. 61/322,148 filed April 8, 2010 and entitled "Surfactant-Free Water-Free Foamable Compositions, Breakable Foams and Their Uses; United States Provisional Application No. 61/349,911 filed May 31, 2010 and entitled "Surfactant-Free Water-Free Foamable Compositions, Breakable Foams and Their Uses; United States Provisional Application No. 61/385,385 filed September 22, 2010 and entitled "Surfactant-Free Water-Free Foamable Compositions, Breakable Foams and Gels and Their Uses; United States Provisional Application No. 61/331,126 filed May 4, 2010 and entitled "Compositions, Gels and Foams with Rheology Modulators and Uses Thereof; and United States Provisional Application No.
61/380,568 filed September 7, 2010 and entitled "Surfactant-Free Water-Free Foamable Compositions and Breakable Foams and Their Uses; all of which are herein incorporated in their entirety by reference.
BACKGROUND
BREAKABLE FOAMS AND THEIR USES
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority under 35 U.S.C.
119(e) to United States Provisional Application No. 61/248,144 filed October 2, 2009 and entitled "Surfactant-Free Water-Free Foamable Compositions, Breakable Foams and Their Uses; United States Provisional Application No. 61/322,148 filed April 8, 2010 and entitled "Surfactant-Free Water-Free Foamable Compositions, Breakable Foams and Their Uses; United States Provisional Application No. 61/349,911 filed May 31, 2010 and entitled "Surfactant-Free Water-Free Foamable Compositions, Breakable Foams and Their Uses; United States Provisional Application No. 61/385,385 filed September 22, 2010 and entitled "Surfactant-Free Water-Free Foamable Compositions, Breakable Foams and Gels and Their Uses; United States Provisional Application No. 61/331,126 filed May 4, 2010 and entitled "Compositions, Gels and Foams with Rheology Modulators and Uses Thereof; and United States Provisional Application No.
61/380,568 filed September 7, 2010 and entitled "Surfactant-Free Water-Free Foamable Compositions and Breakable Foams and Their Uses; all of which are herein incorporated in their entirety by reference.
BACKGROUND
[0002] Foam compositions with high amounts of hydrophobic solvents are little known in the art.
[0003] Foams and, in particular, oleaginous single-phase foams are complicated systems which do not form under all circumstances. Slight shifts in foam composition, such as by the addition of active ingredients or the removal of any of the essential ingredients, may destabilize the foam.
[0004] The prior art teaches oleaginous foam compositions require significant amounts of surface active agents to form and stabilize a foam. These compositions require various standard surfactants, as essential components.
[0005] Surfactants are known as essential ingredients in foam compositions because of their amphiphilic properties and because they are considered essential in forming a foam. However, many surfactants are known to be irritating when left on the skin, as they can extract lipids from the skin, thereby damaging skin barrier and exposing the skin to contact with pro-inflammatory factors. (See for example: Effendy, I. and Maibach, H.I. "Surfactants and Experimental Irritant Contact Dermatitis. " Contact Dermatol., 33 (1995), 217-225). Many surfactants can also react with unstable active agents and lead to their rapid degradation.
[0006] Briefly, the term surfactant has been often loosely used in the art to include substances which do not function effectively as stand alone surfactants to reduce surface tension between two substances or phases. Reduction of surface tension can be significant in foam technology in relation to the ability to create small stable bubbles. In the context herein, the term "standard surfactant" or "customary surfactant" refers to customary non-ionic, anionic, cationic, zwitterionic, amphoteric and amphiphilic surfactants. Many standard surfactants are derivatives of fatty alcohols or fatty acids, such as ethers or esters formed from such fatty alcohols or fatty acids with hydrophilic moieties, such as polyethyleneglycol (PEG). However, a native (non derivatized) fatty alcohol or fatty acid, or wax are not regarded as a standard surfactant.
[0007] In the context herein the term "foam adjuvant" includes only fatty alcohols and fatty acids. These are amphiphatic, and essentially hydrophobic with a minor hydrophilic region. For the purposes of forming an emulsion these foam adjuvants, unlike "standard" or "customary surfactants", are not effective as stand-alone surfactants in foamable emulsion compositions, because of their very weak emulsifying capacity on their own. Fatty alcohols and fatty acids have been loosely described as co-surfactants in foamable emulsion compositions, because they assist customary surfactants to boost foam quality, help evolve the foaming properties and because they stabilize the foam in part because of their property as thickeners.
SUMMARY
SUMMARY
[0008] The present application relates to foamable formulations and foams and their uses comprising hydrophobic solvents. It further relates to hydrophobic solvents with waxes. In particular it relates to waxes that are solid at room temperature. In addition, it relates to formulation with and without an active agent. Surprisingly, the application also relates to foamable formulations and foam without surfactants; and or without surfactants and foam adjuvants; and or without surfactants and polymeric agents; and or without surfactants and foam adjuvants and polymeric agents. In one or more embodiments the hydrophobic solvents are provided as part of a drug carrier. For example certain drugs require hydrophobic solvents in order to solubilize them. In one or more other embodiments, the hydrophobic solvents are provided to facilitate or enhance the transdermal penetration or delivery of a drug. In one or more additional cases, the formulations are provided to have a water barrier effect at a target site, for example where the site of treatment is a damaged skin and the water barrier effect of hydrophobic solvents is desirable. In some embodiments the formulation may have some occlusivity. In some embodiments petrolatum is added to achieve or enhance an occlusive effect.
The present application further relates to compositions comprising hydrophobic solvents and their uses.
The present application further relates to compositions comprising hydrophobic solvents and their uses.
[0009] It is known in the art that foams can easily be formulated based on high amounts of water, in combination with surface active agents, foam adjuvants and polymeric agents. As described in the literature, hydrophobic solvents can have a de-foaming effect which makes the formulation of foams based on hydrophobic solvents - challenging. To overcome this challenge, the prior art requires the use of substantial levels of surfactants that act as efficient foaming agents. The prior art further teaches the incorporation of foam adjuvants, such as fatty alcohols and fatty acids, as foam boosting agents and also the incorporation of polymeric agents (e.g.
gelling agents) as foam stabilizers, which can prolong the collapse time of a foam. Waxes may also be introduced into these surfactant based formulations but as will be appreciated, waxes, which are at ambient temperature can easily precipitate. Surface active agents are known to be irritating, especially ionic surface active agents and repeated use can cause dry skin and so it is desirable to reduce their use in pharmaceutical compositions intended to treat skin or mucosa.
The technical problems to be overcome in formulating carriers and pharmaceutical compositions with hydrophobic solvent (a) without surfactant; and (b) without surfactant and foam adjuvant;
and (c) without polymeric agents and (d) without water are multifold and include finding a suitable substitute for surfactant which provides foam generating properties;
finding a suitable replacement that preferably does not need to have a foam adjuvant present with the surfactant (substitute), which if present would inter alia help to boost the foam and as an aid to the surfactant and preferably does not need to have a polymeric agent present with the surfactant (substitute), which if present would inter alia help prolong stability of the foam. It was surprisingly discovered in the present invention, that surface active agents can be advantageously eliminated and replaced by waxes in the context of hydrophobic solvent based-foams. Waxes possess several advantages over other foaming agents such as excellent skin compatibility, almost no chemical reactivity which ensures active ingredients stability and efficient skin occlusion which helps reducing skin water loss and can enhance skin penetration of active agents. Albeit waxes introduce their own additional problems into formulating foamable compositions and foams, including their tendency to solidify and precipitate out from a formulation, and to increase significantly the viscosity of an oleaginous composition, and to block canister valves, against which the formulations need to be designed so that the formulations are not negatively disturbed upon adding an effective amount of propellant and that the formulations are shakable and are homogenous and can readily reform at least upon mild or reasonable shaking prior to use.
gelling agents) as foam stabilizers, which can prolong the collapse time of a foam. Waxes may also be introduced into these surfactant based formulations but as will be appreciated, waxes, which are at ambient temperature can easily precipitate. Surface active agents are known to be irritating, especially ionic surface active agents and repeated use can cause dry skin and so it is desirable to reduce their use in pharmaceutical compositions intended to treat skin or mucosa.
The technical problems to be overcome in formulating carriers and pharmaceutical compositions with hydrophobic solvent (a) without surfactant; and (b) without surfactant and foam adjuvant;
and (c) without polymeric agents and (d) without water are multifold and include finding a suitable substitute for surfactant which provides foam generating properties;
finding a suitable replacement that preferably does not need to have a foam adjuvant present with the surfactant (substitute), which if present would inter alia help to boost the foam and as an aid to the surfactant and preferably does not need to have a polymeric agent present with the surfactant (substitute), which if present would inter alia help prolong stability of the foam. It was surprisingly discovered in the present invention, that surface active agents can be advantageously eliminated and replaced by waxes in the context of hydrophobic solvent based-foams. Waxes possess several advantages over other foaming agents such as excellent skin compatibility, almost no chemical reactivity which ensures active ingredients stability and efficient skin occlusion which helps reducing skin water loss and can enhance skin penetration of active agents. Albeit waxes introduce their own additional problems into formulating foamable compositions and foams, including their tendency to solidify and precipitate out from a formulation, and to increase significantly the viscosity of an oleaginous composition, and to block canister valves, against which the formulations need to be designed so that the formulations are not negatively disturbed upon adding an effective amount of propellant and that the formulations are shakable and are homogenous and can readily reform at least upon mild or reasonable shaking prior to use.
[0010] In one or more embodiments the drug carrier is formulated for use on sensitive target areas such as sensitive or damages skin areas, wounds, bums, mucosal membranes, body cavities and the eye. In one or more embodiments the composition is intended for use in treatment or prevention of eye infections.
[0011] Unexpectedly, it has been discovered that quality oleaginous formulations and foams can be achieved without the presence of significant amounts of standard surfactants. Also surprisingly it has been discovered that quality oleaginous formulations and foams can be achieved without the presence of significant amounts of foam adjuvants (i.e fatty alcohols and fatty acids) known in the art. Further, unexpectedly, it has been discovered that quality oleaginous formulations and foams can be achieved without the presence of significant amounts of standard polymeric agents (e.g. gelling agents). Thus, in one or more embodiments, there is provided a substantially surfactant-free and substantially foam adjuvant-free oleaginous formulation or foam. In one or more preferred embodiments the oleaginous formulations and foams are free of standard surfactants and foam adjuvants. Thus, in one or more embodiments, there is provided a substantially surfactant free and substantially polymeric agent free oleaginous formulation or foam. In one or more preferred embodiments the oleaginous formulations and foams are free of standard surfactants and polymers. Unexpectedly, it has further been discovered that quality oleaginous formulations and foams can be achieved without the presence of significant amounts of standard surfactants, foam adjuvants and polymeric agents known in the art. Thus, in one or more embodiments, there is provided a substantially surfactant free and substantially foam adjuvant free and substantially polymeric agent free oleaginous formulation or foam. In one or more preferred embodiments the oleaginous formulations and foams are free of surface active agents and foam adjuvants and polymeric agents. Moreover, it has been further discovered that these formulations and foams can be achieved over a large range of hydrophobic solvent content. There is thus provided easy to use, stable and non-irritating topical foam formulations, and pharmaceutical compositions thereof, containing a stable or stabilized active pharmaceutical or cosmetic agent having a therapeutic or beneficial effect, intended for treatment of dermal and mucosal tissues free or substantially free of standard surface active agents and foam adjuvants.
[0012] In one or more embodiments there is provided a safe and effective foamable carrier composition and foam comprising a hydrophobic solvent, an oleaginous foaming agent comprising a wax and a liquefied or compressed gas propellant. In certain embodiments, the concentration of the propellant is about I% to about 30% by weight of the total composition. In other certain embodiments, the concentration of the propellant is about 3% to about 25 % by weight of the total composition; or about 7% to about 17 %; or about 10% to about 14 %. In additional embodiments there is provided a safe and effective foamable pharmaceutical or cosmetic composition and foam comprising an effective amount of a pharmaceutical or cosmetic active agent, a hydrophobic solvent, a foaming agent comprising of a wax and a liquefied or compressed gas propellant. The percent by weight is based on weight foamable composition;
where the ratio of composition other than propellant to propellant is from about 100:1 to about 100:30; or from about 100:3 to about 100:25; or from about 100:7 to about 100:17; or from about 100:10 to about 100:14 The composition does not contain a surfactant or a foam adjuvant; and the foaming effect is achieved by the addition of the foamer agent, as specified herein. The hydrophobic solvent is present in a substantial amount. In one or more embodiments the hydrophobic solvent is at a concentration between about 40% to about 92% or about 50% to about 90% by weight, or about 40% to about 95% by weight or about 70% to about 90% by weight.. In alternative embodiments the formulation is formulated without propellant and delivered as a gel, ointment or rub. The total weight of the foaming agent which is a wax is about 8% to about 50% by weight of a wax. In one or more embodiments the amount of wax is less than 55%; or is less than about 54% ; or is less than about 53%; or is less than about 52%; or is less than about 51%; or is less than about 50% by weight; or is less than about 45%; or is less than about 40%; or is less than about 35%; or is less than about 30%; or is less than about 25%;
or is less than about 20%; or is less than about 15% by weight. In one or more alternative embodiments the formulation comprises 0% to about 550% wax and about 45% to about 95%
hydrophobic solvent. In certain embodiments the wax is about I% to about 20%
and the hydrophobic solvent is about 75% to about 94%. In certain embodiments the wax is about 21% to about 40% and the hydrophobic solvent is about 55% to about 74%. In certain embodiments the wax is about 41% to about 60% and the hydrophobic solvent is about 35% to about 54%. As will be appreciated from the above illustrative examples as the amount of wax is increased the amount of hydrophobic solvent is reduced. Accordingly, differing amounts of wax other than the amounts specified can be contemplated with a parallel increase or decrease in solvent as appropriate. In one or more embodiments their total amount (wax plus solvent) is between about 95% and about 100%. In one or more other embodiments the total amount is between about 92%
and about 100%; or between about 90% and about 100%; between about 85% and about 100%;
or between about 90% and about 95%; or between about 90% and about 98% or between about 85% and about 95%; or between about 85% and about 98%. .
where the ratio of composition other than propellant to propellant is from about 100:1 to about 100:30; or from about 100:3 to about 100:25; or from about 100:7 to about 100:17; or from about 100:10 to about 100:14 The composition does not contain a surfactant or a foam adjuvant; and the foaming effect is achieved by the addition of the foamer agent, as specified herein. The hydrophobic solvent is present in a substantial amount. In one or more embodiments the hydrophobic solvent is at a concentration between about 40% to about 92% or about 50% to about 90% by weight, or about 40% to about 95% by weight or about 70% to about 90% by weight.. In alternative embodiments the formulation is formulated without propellant and delivered as a gel, ointment or rub. The total weight of the foaming agent which is a wax is about 8% to about 50% by weight of a wax. In one or more embodiments the amount of wax is less than 55%; or is less than about 54% ; or is less than about 53%; or is less than about 52%; or is less than about 51%; or is less than about 50% by weight; or is less than about 45%; or is less than about 40%; or is less than about 35%; or is less than about 30%; or is less than about 25%;
or is less than about 20%; or is less than about 15% by weight. In one or more alternative embodiments the formulation comprises 0% to about 550% wax and about 45% to about 95%
hydrophobic solvent. In certain embodiments the wax is about I% to about 20%
and the hydrophobic solvent is about 75% to about 94%. In certain embodiments the wax is about 21% to about 40% and the hydrophobic solvent is about 55% to about 74%. In certain embodiments the wax is about 41% to about 60% and the hydrophobic solvent is about 35% to about 54%. As will be appreciated from the above illustrative examples as the amount of wax is increased the amount of hydrophobic solvent is reduced. Accordingly, differing amounts of wax other than the amounts specified can be contemplated with a parallel increase or decrease in solvent as appropriate. In one or more embodiments their total amount (wax plus solvent) is between about 95% and about 100%. In one or more other embodiments the total amount is between about 92%
and about 100%; or between about 90% and about 100%; between about 85% and about 100%;
or between about 90% and about 95%; or between about 90% and about 98% or between about 85% and about 95%; or between about 85% and about 98%. .
[0013] Upon dispensing the foamable carrier composition forms a breakable foam that is stable, yet breaks easily upon application of shear force. In one or more embodiments the composition is used for intradermal delivery of the active agent into the skin with minimal or negligible transdermal delivery. In one or more alternative embodiments a formulation is provided to achieve intra mucosal delivery. In certain embodiments the composition provides for transdermal delivery. In one or more embodiments the composition can be used for prevention of a disease or disorder. The composition or foam is applied to a target surface or area in or on which prevention is sought. In other embodiments the composition or foam is used to treat or ameliorate a disease or disorder. In still further embodiments it may be used to provide a period of remission from the disease or disorder.
[0014] According to an embodiment the one or more active agents is selected from the group consisting of adipic acid, an acaricide, an active herbal extract, an age spot and keratose removing agent, an allergen, an alpha hydroxyl acid, an analgesic agent, an androgen, an anesthetic, an anti wrinkle agent, an antiacne agent, an antiaging agent, an antiallergic agent, an antiandrogen agent, an antiapoptotic agent, an antibacterial agent, an antibiotic, an antibiotic agent, an antiburn agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic anent, an antifungal agent, an antihelminth agent, an antihistamine, an anti-hyperkeratosis agent, an anti-infective agent, an antiinflammatory agent, an antiirritant, an antilipemic agent, an antimicrobial agent, an antimycotic agent, an antioxidant, an antiparasitic agent, an anti-photoaging agent, an anti-photodamaging agent, an antiproliferative agent, an antipruritic agent, an antipsoriatic agent, an antirosacea agent, an antiseborrheic agent, an antiseptic agent, an antiswelling agent, an antiviral agent, an anti-wart agent, an anti-wrinkle agent, an anti-yeast agent, an astringent, azelaic acid, benzoyl chloride, benzoyl peroxide, a beta-hydroxy acid, calcitriol, calcium hypochlorite, carbon, a cardiovascular agent, a chemotherapeutic agent, a corticosteroid, a dicarboxylic acid, a dihydrotestosterone inhibitor, a disinfectant, doxycycline, an estrogen, a fungicide, fumaric acid, glycolic acid, a hair growth regulator, a haptene, a herbal extract (comprising an active substance), a hormonal agent, a hormone, a hydroxy acid, an immunogenic substance, an immunomodulator, an immunoregulating agent, an immunostimulant, an immunosuppressant, an immunosuppressive agent, an insect repellent, an insecticide, iron oxide, a keratolytic agent, lactic acid, a lactam, lidocaine, a local anesthetic agent, a lubricating agent, a masking agent, a metal, a metal oxide, minocycline, a mitocide, mometasone fuorate, a neuropeptide, a non-steroidal anti-inflammatory agent, an organo-beryllium compound, an organo-metallic compound, an oxidizing agent, and organo-boron compound, a pediculicide, a peptide, a pesticide, a photodynamic therapy agent, a progesterone, a prostaglandin, a protein, a radical scavenger, a refatting agent, a retinoid, a sedative agent, a scabicide, sebacic acid, a sedative, a sedative agent, a self tanning agent, silicone oxide, silver, a silver compound, a skin protective agent, a skin whitening agent, a steroid, a steroid hormone, a steroidal anti-inflammatory agent, talc, titanium dioxide, a tellurium compound, a testosterone inhibitor, a tetracycline antibiotic, urea, a urea derivative, a vasoactive agent, a vasoconstrictor, a vasodilator, a vitamin, a vitamin A, a vitamin A
derivative, a vitamin B, a vitamin B derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D analog, a vitamin D derivative, a vitamin E , a vitamin E derivative, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K derivative, a wart remover, a wound healing agent, zinc oxide, zirconium oxide.. According to a further embodiment the active agent is a tetracycline antibiotic. In certain embodiments the tetracycline is minocycline. In certain embodiments the tetracycline is doxycycline. In certain embodiments the active agent is selected from a group consisting of calcitriol, mometasone fuorate, calcitriol and lidocaine. According to a further embodiment the active agent is chemically stable for at least two months and where the active agent is compatible with the other ingredients. According to a further embodiment the active agent is chemically stable for at least six months; or for at least nine months for at least twelve months; or for at least fifteen months; or for at least eighteen months; or for at least twenty one months; or for at least twenty four months.
derivative, a vitamin B, a vitamin B derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D analog, a vitamin D derivative, a vitamin E , a vitamin E derivative, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K derivative, a wart remover, a wound healing agent, zinc oxide, zirconium oxide.. According to a further embodiment the active agent is a tetracycline antibiotic. In certain embodiments the tetracycline is minocycline. In certain embodiments the tetracycline is doxycycline. In certain embodiments the active agent is selected from a group consisting of calcitriol, mometasone fuorate, calcitriol and lidocaine. According to a further embodiment the active agent is chemically stable for at least two months and where the active agent is compatible with the other ingredients. According to a further embodiment the active agent is chemically stable for at least six months; or for at least nine months for at least twelve months; or for at least fifteen months; or for at least eighteen months; or for at least twenty one months; or for at least twenty four months.
[0015] As is known to one skilled in the art, in some instances a specific active agent may have more than one activity, function or effect.
[0016] In certain embodiments, the inclusion of two or more therapeutic agents in the foamable pharmaceutical composition is desirable.
[0017] In one or more embodiments the foamable composition further comprises a fatty alcohol. In one or more embodiments the fatty alcohol is a therapeutically active fatty alcohol.
The fatty alcohol can be a straight chain fatty alcohol, a saturated fatty alcohol, an unsaturated fatty alcohol, a hydroxyl substituted fatty alcohol or a branched fatty alcohol.
The fatty alcohol can be a straight chain fatty alcohol, a saturated fatty alcohol, an unsaturated fatty alcohol, a hydroxyl substituted fatty alcohol or a branched fatty alcohol.
[0018] In an embodiment, the foamable composition further comprises a fatty acid. The fatty acid can be a straight chain fatty acid, a saturated fatty acid, an unsaturated fatty acid, a hydroxyl fatty acid or a branched fatty acid. In an embodiment the fatty acid is a therapeutically active fatty acid.
[0019] In an embodiment, the foamable composition comprises a foaming agent which is a wax. The wax can be a liquid wax, a solid wax, an animal wax, a vegetable wax, a mineral wax, a natural wax or a synthetic wax. In an embodiment the wax is selected from a list comprising paraffin wax, beeswax, hydrogenated castor oil or mixtures thereof. In one or more embodiments there is provided a composition comprising a paraffin wax. In one or more embodiments the paraffin wax can have a melting point form about 37 C. In one or more embodiments the paraffin wax comprises of alkane chains of between about C20H42 to C40H82. In one or more embodiments the alkane chains are substantially straight chain. In some embodiments branched or unsaturated molecules can be present. Branched chains are sometimes referred to as isoparaffins. In one or more embodiments the paraffin wax can be selected from the group consisting of paraffin wax 58-62 C, paraffin wax 51-53 C, and paraffin wax 42-44 C, or mixtures thereof. In one or more other embodiments other melting point ranges can be selected such as 125 F to 135 F; 127 F to 130 F; 130 F to 135 F; 135 F to 145 F ; 140 F to 145 F; 150 F to 155 F; 150 F to 165 F; 160 F to 165 F; or such as 43-46 C; 46-53 C; 48-50 C;
52-54 C; 53-55 C; 54-57 C; 54-58 C; 58-60 C; 59-61 C; 60-62 C; 62-66 C; 65-68 C; or any other similar or relative range(s) or mixtures thereof. In an embodiment the wax is fully refined. In an embodiment it is suitable for cosmetic use. In an embodiment it is suitable for pharmaceutical use. In an embodiment the paraffin wax is soft.
52-54 C; 53-55 C; 54-57 C; 54-58 C; 58-60 C; 59-61 C; 60-62 C; 62-66 C; 65-68 C; or any other similar or relative range(s) or mixtures thereof. In an embodiment the wax is fully refined. In an embodiment it is suitable for cosmetic use. In an embodiment it is suitable for pharmaceutical use. In an embodiment the paraffin wax is soft.
[0020] In one or more embodiments the drug carrier is formulated substantially free of short chain alcohols, such as, ethanol, propanol or butanol. In one or more embodiments the drug carrier is formulated essentially free of short chain alcohols. In one or more specific embodiments the drug carrier is formulated essentially free of fatty alcohols and or fatty acids. In one or more other specific embodiments the drug carrier is formulated essentially free of polyols.
In one or more other specific embodiments the drug carrier is formulated essentially free of surfactants and or short chain alcohols and or polyols and or fatty acids and or fatty alcohols. . In one or more other specific embodiments the drug carrier is formulated substantially free of surfactants and or short chain alcohols and or polyols and or fatty acids and or fatty alcohols.
In one or more other specific embodiments the drug carrier is formulated essentially free of surfactants and or short chain alcohols and or polyols and or fatty acids and or fatty alcohols. . In one or more other specific embodiments the drug carrier is formulated substantially free of surfactants and or short chain alcohols and or polyols and or fatty acids and or fatty alcohols.
[0021] In one or more embodiments there is provided a composition which is essentially waterless. In one or more embodiments there is provided a composition which is surfactant free.
In one or more embodiments there is provided a surfactant free composition that is also foam adjuvant free, and or polymer free. In one or more embodiments there is provided a surfactant free composition that is also free of short chain alcohols and or polyol-free.
In one or more embodiments there is provided a surfactant free composition that is also foam adjuvant free, and or polymer free. In one or more embodiments there is provided a surfactant free composition that is also free of short chain alcohols and or polyol-free.
[0022] In one or more embodiments there is provided a composition comprising a propellant having a vapor pressure between about 10 psi and about 130 psi. In one or more embodiments there is provided a composition comprising a propellant which is hydrocarbon propellant or a hydrofluorocarbon or another environmentally acceptable propellant.
[0023] In one or more embodiments there is provided a single phase composition.
[0024] In one or more embodiments there is provided a composition comprising a hydrophobic solvent which is a liquid oil, selected from the group consisting of hydrocarbon oils, mineral oil, liquid paraffin, isoparaffin, polyalphaolefin, polyolefin, polyisobutylene, synthetic isoalkane, isohexadecane isododecane, ester oils, alkyl benzoate, alkyl octanoate, C 12-C 15 alkyl benzoate, Cl2-C 15 alkyl octanoate, arachidyl behenate, arachidyl propionate, benzyl laurate, benzyl myristate, benzyl palmitate, bis (octyldodecyl stearoyl) dimer dilinoleate, butyl myristate, butyl stearate, cetearyl ethylhexanoate, cetearyl isononanoate, cetyl acetate, cetyl ethylhexanoate, cetyl lactate, cetyl myristate, cetyl octanoate, cetyl palmitate, cetyl ricinoleate, decyl oleate, diethyleneglycol diethylhexanoate, diethyleneglycol dioctanoate, diethyleneglycol diisononanoate, diethyleneglycol diisononanoate, diethylhexanoate, diethylhexyl adipate, diethylhexyl malate, diethylhexyl succinate, diisopropyl adipate, diisopropyl dimerate, diisopropyl sebacate, diisosteary dimer dilinoleate, diisostearyl fumerate, dioctyl malate, dioctyl sebacate, dodecyl oleate, ethylhexyl palmitate, ester derivatives of lanolic acid, ethylhexyl cocoate, ethylhexyl ethylhexanoate, ethylhexyl hydroxystarate, ethylhexyl isononanoate, ethylhexyl palmytate, ethylhexyl pelargonate, ethylhexyl stearate, hexadecyl stearate, hexyl laurate, isoamyl laurate, isocetyl isocetyl behenate, isocetyl lanolate, isocetyl palmitate, isocetyl stearate, isocetyl salicylate, isocetyl stearate, isocetyl stearoyl stearate, isocetearyl octanoate, isodecyl ethylhexanoate, isodecyl isononanoate, isodecyl oleate, isononyl isononanoate, isodecyl oleate, isohexyl decanoate, isononyl octanoate, isopropyl isostearate, isopropyl lanolate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearyl behenate, isosteary citrate, isostearyl erucate, isostearyl glycolate, isostearyl isononanoate, isostearyl isostearate, isostearyl lactate, isostearyl linoleate, isostearyl linolenate, isostearyl malate, isostearyl neopentanoate, isostearyl palmitate, isosteary salicylate, isosteary tartarate, isotridecyl isononanoate, isotridecyl isononanoate, lauryl lactate, myristyl lactate, myristyl myristate, myristyl neopentanoate, myristyl propionate, octyldodecyl myristate, neopentylglycol dicaprate, octyl dodecanol, octyl stearate, octyl palmitate, octyldodecyl behenate, octyldodecyl hydroxystearate, octyldodecyl myristate, octyldodecyl stearoyl stearate, oleyl erucate, oleyl lactate, oleyl oleate, propyl myristate, propylene glycol myristyl ether acetate, propylene glycol dicaprate, propylene glycol dicaprylate, propylene glycol dicaprylate, maleated soybean oil, stearyl caprate, stearyl heptanoate, stearyl propionate, tocopheryl acetate, tocopheryl linoleate, glyceryl oleate, tridecyl ethylhexanoate, tridecyl isononanoate and triisocetyl citrate, liquid triglycerides, oils of plant origin, alexandria laurel tree oil, avocado oil, apricot stone oil, barley oil, borage seed oil, calendula oil, canelle nut tree oil, canola oil, caprylic/capric triglyceride castor oil, coconut oil, corn oil, cotton oil, cottonseed oil, evening primrose oil, flaxseed oil, groundnut oil, hazelnut oil, glycereth triacetate, glycerol triheptanoate, glyceryl trioctanoate, glyceryl triundecanoate, hempseed oil, jojoba oil, lucerne oil, maize germ oil, marrow oil, millet oil, neopentylglycol dicaprylate/dicaprate, olive oil, palm oil, passionflower oil, pentaerythrityl tetrastearate, poppy oil, propylene glycol ricinoleate, rapeseed oil, rye oil, safflower oil, sesame oil, shea butter, soya oil, soybean oil, sweet almond oil, sunflower oil, sysymbrium oil, syzigium aromaticum oil, tea tree oil, walnut oil, wheat germ glycerides and wheat germ oil, an essential oil, PPG alkyl ethers, PPG-2 butyl ether, PPG-4 butyl ether, PPG-5 butyl ether, PPG-9 butyl ether, PPG-12 butyl ether, PPG-14 butyl ether, PPG-15 butyl ether, PPG-15 stearyl ether, PPG-16 butyl ether, PPG- 17 butyl ether, PPG- 18 butyl ether, PPG-20 butyl ether, PPG-22 butyl ether, PPG-24 butyl ether, PPG-26 butyl ether, PPG-30 butyl ether, PPG-33 butyl ether, PPG-40 butyl ether, PPG-52 butyl ether, PPG-53 butyl ether, PPG-10 cetyl ether, PPG-28 cetyl ether, PPG-30 cetyl ether, PPG-50 cetyl ether, PPG-30 isocetyl ether, PPG-4 lauryl ether, PPG-7 lauryl ether, PPG-2 methyl ether, PPG-3 methyl ether, PPG-3 myristyl ether, PPG-4 myristyl ether, PPG-10 oleyl ether, PPG-20 oleyl ether, PPG-23 oleyl ether, PPG-30 oleyl ether, PPG-37 oleyl ether, PPG-40 butyl ether, PPG-50 oleyl ether and PPG-11 stearyl ether. Preferred PPG
alky ethers according to the present invention include PPG-15 stearyl ether, PPG-2 butyl ether and PPG-9-13 butyl ether, oils from animal origin, herring oil, cod-liver oil and salmon oil, a therapeutic oil, manuka oil, rosehip oil, tea tree oil, basil oil, camphor oil, cardamom oil, carrot oil, citronella oil, clary sage oil, clove oil, cypress oil, frankincense oil, ginger oil, grapefruit oil, hyssop oil, jasmine oil, lavender oil, lemon oil, mandarin oil, marjoram oil, myrrh oil, neroli oil, nutmeg oil, petitgrain oil, sage oil, tangerine oil, vanilla oil verbena oil, silicone oils, cyclomethicone, dimethicone, polyalkyl siloxane, polyaryl siloxane, polyalkylaryl siloxane, polyether siloxane copolymer, poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer, dimethyl polysiloxane, epoxy-modified silicone oil, fatty acid-modified silicone oil, fluoro group-modified silicone oil, methylphenylpolysiloxane, phenyl trimethicone, polyether group-modified silicone oil cyclomethicone, cyclotetrasiloxane, cyclohexasiloxane, phyenyltrimethicone, Dow coming 246 Fluid (d6+d5) (cyclohexasiloxane & cyclopentasiloxane), Dow Coming 244 Fluid (cyclotetrasiloxane), Cyclomethicone 5-NF (cyclopentasiloxane), stearyl dimethicone, phenyltrimethicone, cetyl dimethicone, caprylyl methicone, PEG/PPG 18/18 dimethicone, or dimethiconol, capric/caprylic triglycerides, cyclomethicone; isopropyl myristate, isopropyl palmitate, PPG-15 stearyl ether; octyldodecanol; isohexadecanol, diisopropyl adipate; cetearyl octanoate; ; MCT oil; heavy mineral oil; light mineral oil; coconut oil and soybean oil, an unsaturated or polyunsaturated oil, a diglyceride, a PPG alkyl ether or mixtures thereof.
alky ethers according to the present invention include PPG-15 stearyl ether, PPG-2 butyl ether and PPG-9-13 butyl ether, oils from animal origin, herring oil, cod-liver oil and salmon oil, a therapeutic oil, manuka oil, rosehip oil, tea tree oil, basil oil, camphor oil, cardamom oil, carrot oil, citronella oil, clary sage oil, clove oil, cypress oil, frankincense oil, ginger oil, grapefruit oil, hyssop oil, jasmine oil, lavender oil, lemon oil, mandarin oil, marjoram oil, myrrh oil, neroli oil, nutmeg oil, petitgrain oil, sage oil, tangerine oil, vanilla oil verbena oil, silicone oils, cyclomethicone, dimethicone, polyalkyl siloxane, polyaryl siloxane, polyalkylaryl siloxane, polyether siloxane copolymer, poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer, dimethyl polysiloxane, epoxy-modified silicone oil, fatty acid-modified silicone oil, fluoro group-modified silicone oil, methylphenylpolysiloxane, phenyl trimethicone, polyether group-modified silicone oil cyclomethicone, cyclotetrasiloxane, cyclohexasiloxane, phyenyltrimethicone, Dow coming 246 Fluid (d6+d5) (cyclohexasiloxane & cyclopentasiloxane), Dow Coming 244 Fluid (cyclotetrasiloxane), Cyclomethicone 5-NF (cyclopentasiloxane), stearyl dimethicone, phenyltrimethicone, cetyl dimethicone, caprylyl methicone, PEG/PPG 18/18 dimethicone, or dimethiconol, capric/caprylic triglycerides, cyclomethicone; isopropyl myristate, isopropyl palmitate, PPG-15 stearyl ether; octyldodecanol; isohexadecanol, diisopropyl adipate; cetearyl octanoate; ; MCT oil; heavy mineral oil; light mineral oil; coconut oil and soybean oil, an unsaturated or polyunsaturated oil, a diglyceride, a PPG alkyl ether or mixtures thereof.
[0025] According to additional embodiments there is provided a method of producing a foamable composition, including:
1. providing a foamable therapeutic composition including a therapeutic agent at a therapeutically effective concentration, a hydrophobic solvent, for example, at a concentration of about 50% to about 90% by weight and a foaming agent including a wax;
2. introducing the foamable composition in an aerosol packaging assembly, comprising of a container, suitable for containing a pressurized product and a valve, capable of extruding a foam; and 3. introducing to the aerosol packaging assembly a liquefied or compressed gas propellant at a concentration.
1. providing a foamable therapeutic composition including a therapeutic agent at a therapeutically effective concentration, a hydrophobic solvent, for example, at a concentration of about 50% to about 90% by weight and a foaming agent including a wax;
2. introducing the foamable composition in an aerosol packaging assembly, comprising of a container, suitable for containing a pressurized product and a valve, capable of extruding a foam; and 3. introducing to the aerosol packaging assembly a liquefied or compressed gas propellant at a concentration.
[0026] According to additional embodiments the formulation comprises about 1%
to about 18% wax and about 80% to about 94% hydrophobic solvent. In further embodiments wax may be in excess of 18%.
to about 18% wax and about 80% to about 94% hydrophobic solvent. In further embodiments wax may be in excess of 18%.
[0027] In one or more embodiments there is provided a method of preventing or treating or alleviating a dermatological or mucosal disorder, comprising: applying a substantially surfactant free foamable composition to a surface having or anticipated to have a dermatological or mucosal disorder or disease in need of treatment. In one or more embodiments the active agent is a placebo.
[0028] In one or more embodiments there is provided use of a substantially surfactant free foamable composition for preventing or treating or alleviating a dermatological or mucosal disorder.
[0029] In one or more embodiments the disorder is selected form the group consisting of abscess, acne, acne conglobata, acne fulminans, acne vulgaris, acne scars, acute febrile neutrophilic dermatosis, acute lymphangitis, allergic contact dermatitis, alopecia, athlete's foot, atopic dermatitis, bacterial skin infections, baldness, basal cell carcinoma, blisters, bromhidrosis, bullous pemphigoid, bum, calluses candidiasis, carbuncles, cellulitis, chemical bums, chicken pox, cholesteatoma, cholinergic urticaria, chronic effects of sunlight, cold sores, cold urticaria, comedones, corns, creeping eruption, cutaneous abscess, cutaneous larva migrans, cutaneous myiasis, dark spots, delusional parasitosis, Dercum disease, dermatitis, dermatitis herpetiformis, dermatological pain, dermatological inflammation, dermographism, dermatophytoses, drug eruptions and reactions, dyshidrotic eczema, ectodermal dysplasia, eczema, ecthyma, epidermoid cyst, epidermal necrolysis, erysipelas, erysipelas, erythrasma, exfoliative dermatitis, erythema multiforme, erythema nodosum, folliculitis, fungal nail infections, fungal skin infections, furuncles, gangrene, genital herpes, granuloma annulare, head lice, hidradenitis suppurativa, hives, folliculitis, hirsutism, hyperhidrosis, hypohidrosis, ichthyosis, impetigo, inflammatory acne, ingrown nails, intertrigo, irritant contact dermatitis, ischemic necrosis, itching, jock itch, Kaposi's sarcoma, keratosis pilaris, lichen simplex chronicus, lichen planus, lichen sclerosus, lymphadenitis, lymphadenitis, lymphangitis, malignant melanoma, mastocytosis, measles, melanoma, melanoma, miliaria, moles, molluscum contagiosum, MRSA, necrotizing subcutaneous infection, necrotizing fasciitis, necrotizing myositis, nodular papulopustular acne, non-inflammatory acne, nummular dermatitis, oral herpes, panniculitis, parapsoriasis paronychia, parasitic skin infections, pemphigus, photo-allergy, photo-damage, photo-irritation, photosensitivity, papules, pediculosis, perioral dermatitis, pimples, pityriasis rosea, pityriasis Lichenoides, pityriasis rosea, pityriasis rubra pilaris, poison ivy, poison oak post-operative or post-surgical skin conditions, pressure ulcers, pressure urticaria, pruritis, pseudofolliculitis barbae, psoriasis, PUPPP, purpura, pustules, pyogenic granuloma, rash, ringworm, rosacea, roseola, rubella, scabies, scalded skin syndrome, scarring, scleroderma, sebaceous cyst, seborrheic dermatitis, seborrheic keratosis, shingles, skin aging, skin cancer, skin neoplasia, skin neoplasms, skin rash, skin ulcers, squamous cell carcinoma, staphylococcal scalded skin syndrome, stasis dermatitis, Stevens-Johnson syndrome, sunburn, sun spots, thermal bums, tinea corporis, tinea cruris, tinea pedis, tinea versicolor, toxic epidermal necrolysis, trauma or injury to the skin, varicella zoster virus, vitamin D deficiency, viral skin infections, vitiligo, warts, water hives, wrinkles, xerosis, yeast skin infections and zoster.
[0030] According to further embodiments there is provided a method of preventing, treating ameliorating or eliminating a disorder by selecting and releasing on to a convenient surface a safe and effective pharmaceutical or cosmetic foamable composition comprising an effective amount of a pharmaceutical or cosmetic agent, a hydrophobic solvent, a foaming agent comprising a wax and a liquefied or compressed gas propellant at a concentration of about 1% to about 30% by weight of the total composition; directing the released foam on to a target on a patient in need or anticipated need; applying a shear force to and spreading the foam over the target surface such that after a simple rub the foam is no longer visible to the naked eye as it is absorbed rapidly on to the target surface.
[0031] According to one of more further embodiments the disorder treated by the foamable composition is selected from the group consisting of a dermatose, a dermatitis, a vaginal disorder, a vulvar disorder, an anal disorder, a disorder of a body cavity, an ear disorder, a disorder of the nose, a disorder of the respiratory system, a bacterial infection, a fungal infection, a viral infection, dermatosis, dermatitis, parasitic infections, disorders of hair follicles and sebaceous glands, scaling papular diseases, benign tumors, malignant tumors, reactions to sunlight, bullous diseases, pigmentation disorders, disorders of cornification, pressure sores, disorders of sweating, inflammatory reactions, xerosis, ichthyosis, an allergy, a bum, a wound, a cut, a chlamydia infection, a gonorrhea infection, hepatitis B, herpes, HIV/AIDS, human papillomavirus (HPV), genital warts, bacterial vaginosis, candidiasis, chancroid, granuloma Inguinale, lymphogranloma venereum, mucopurulent cervicitis (MPC), molluscum contagiosum, nongonococcal urethritis (NGU), trichomoniasis, vulvar disorders, vulvodynia, vulvar pain, a yeast infection, vulvar dystrophy, vulvar intraepithelial neoplasia (VIN), contact dermatitis, osteoarthritis, joint pain, an hormonal disorder, a pelvic inflammation, endometritis, salpingitis, oophoritis, genital cancer, cancer of the cervix, cancer of the vulva, cancer of the vagina, vaginal dryness, dyspareunia, an anal and rectal disease, an anal abscess/fistula, anal cancer, an anal fissure, an anal wart, Crohn's disease, hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation, polyps of the colon and rectum.
DETAILED DESCRIPTION
Foamable composition and foam properties
DETAILED DESCRIPTION
Foamable composition and foam properties
[0032] The ability to achieve quality foam with a substantial concentration of hydrophobic solvent without a surfactant and without a foam adjuvant and without a polymer is surprising, because usually, such solvents are not prone to creating a foam. The challenge is not just to achieve a quality foam but also to attain a formulation that will satisfy a plurality of two, three, four, five, six or more of the following property specifications simultaneously.
[0033] Notably, the pressurized composition is flowable and releases a foam freely, even though it might be expected that such concentrations of wax would make the hydrophobic solvent very viscous or'semi-solid'.
1. Uniformity: The composition should be formulated so that it is and can remain uniform upon shaking and that it can reconstitute upon shaking without phase separation or precipitation over a reasonable time. This property is of importance when the product is intended to be a pharmaceutical product.
2. Flowability: The composition, when placed in an aerosol container and pressurized with a propellant should be flowable such that it can be expelled through the canister valve. It should preferably also be shakable inside the container. These requirements create a formulation challenge, because non-viscous flowable and shakable compositions are prone to undergo phase separation or precipitation.
3. Quality: Upon release from the can, the composition should generate a foam of good or excellent quality having low density and small bubble size.
4. Stability/Breakability: The fine balance between stability and breakability of the foam coming out of the container is very delicate: on one hand the foam should preferable not be "quick breaking", i.e., it should be at least short term stable upon release from the pressurized container and not break as a result of exposure to skin temperature; and on the other hand, it should be "breakable", i.e., it should spread easily, break down and absorb into the skin or membrane upon application of mild shear force.
5. Skin Feeling: To ensure patient compliance the skin feeling after application should be pleasant, and greasy or waxy residues should be minimal.
6. Non-irritating: The above requirements should be achieved with the awareness that formulation excipients, especially surfactants, can be irritating, and should preferably be eliminated from the composition or reduced as much as possible.
7. Delivery: Finally, the composition should also be designed to ensure efficient delivery of a therapeutic agent into the target site of treatment.
8. Compatibility: The components of the composition should be compatible and not react with an active agent.
1. Uniformity: The composition should be formulated so that it is and can remain uniform upon shaking and that it can reconstitute upon shaking without phase separation or precipitation over a reasonable time. This property is of importance when the product is intended to be a pharmaceutical product.
2. Flowability: The composition, when placed in an aerosol container and pressurized with a propellant should be flowable such that it can be expelled through the canister valve. It should preferably also be shakable inside the container. These requirements create a formulation challenge, because non-viscous flowable and shakable compositions are prone to undergo phase separation or precipitation.
3. Quality: Upon release from the can, the composition should generate a foam of good or excellent quality having low density and small bubble size.
4. Stability/Breakability: The fine balance between stability and breakability of the foam coming out of the container is very delicate: on one hand the foam should preferable not be "quick breaking", i.e., it should be at least short term stable upon release from the pressurized container and not break as a result of exposure to skin temperature; and on the other hand, it should be "breakable", i.e., it should spread easily, break down and absorb into the skin or membrane upon application of mild shear force.
5. Skin Feeling: To ensure patient compliance the skin feeling after application should be pleasant, and greasy or waxy residues should be minimal.
6. Non-irritating: The above requirements should be achieved with the awareness that formulation excipients, especially surfactants, can be irritating, and should preferably be eliminated from the composition or reduced as much as possible.
7. Delivery: Finally, the composition should also be designed to ensure efficient delivery of a therapeutic agent into the target site of treatment.
8. Compatibility: The components of the composition should be compatible and not react with an active agent.
[0034] Based on extensive investigations and trial and error experiments, it has been found that such properties can be achieved for formulations as described below and which are further advantageous because of the ability of hydrophobic solvents to dissolve or suspend certain active agents while providing an environment for the active agent which assists in preventing their degradation.
Compositions
Compositions
[0035] All % values are provided on a weight (w/w) basis.
[0036] In one or more embodiments there is provided a foamable carrier composition including:
1. a hydrophobic solvent 2. a foaming agent comprising a wax;
3. a liquefied or compressed gas propellant.
Waxes
1. a hydrophobic solvent 2. a foaming agent comprising a wax;
3. a liquefied or compressed gas propellant.
Waxes
[0037] In one or more embodiments the wax includes a paraffin wax. In one or more embodiments the paraffin wax includes a paraffin wax having a melting point or melting point range somewhere in between about 47 C to about 64 C. In one or more embodiments the paraffin wax includes a paraffin wax having a melting point of about 58 C to 62 C. In one or more embodiments the paraffin wax includes a paraffin wax having a melting point of about 51 C to 53 C. In one or more embodiments the paraffin wax includes a paraffin wax having a melting point of about 42 C to 44 C. In one or more embodiments the wax includes a beeswax.
In one or more embodiments the wax includes a hydrogenated caster oil, which is a wax.
In one or more embodiments the wax includes a hydrogenated caster oil, which is a wax.
[0038] Paraffin waxes are primarily mixtures of solid saturated hydrocarbons having the general formula CnH(2n+2).
[0039] Unexpectedly it was found that paraffin waxes could form quality foam with oils without the assistance of surfactants, and/or foam adjuvants and/or polymers.
Without being bound to a specific theory, the ability of paraffin wax to facilitate the formation of quality stable breakable foam with oils appears to relate to its unique molecular structure and size and resultant Van der Waals forces. Paraffin waxes are comprised primarily of long straight chain molecules having chains consisting of between about 20 to about 40 carbons. Higher melting point paraffin waxes will be expected to have a higher proportion of longer chains than lower melting waxes.
Introduction of branched chains may result in a reduction of melting point.
Without being bound to a specific theory, such long hydrocarbon chains exhibit momentary asymmetry in the electron distribution resulting in temporary dipoles that induce similar dipoles in nearby molecules (Van der Waals forces). This phenomenon is especially prevalent in long molecules like paraffin wax, and less so in the shorter (but otherwise similar) mineral oil.
Without being bound to a specific theory, the ability of paraffin wax to facilitate the formation of quality stable breakable foam with oils appears to relate to its unique molecular structure and size and resultant Van der Waals forces. Paraffin waxes are comprised primarily of long straight chain molecules having chains consisting of between about 20 to about 40 carbons. Higher melting point paraffin waxes will be expected to have a higher proportion of longer chains than lower melting waxes.
Introduction of branched chains may result in a reduction of melting point.
Without being bound to a specific theory, such long hydrocarbon chains exhibit momentary asymmetry in the electron distribution resulting in temporary dipoles that induce similar dipoles in nearby molecules (Van der Waals forces). This phenomenon is especially prevalent in long molecules like paraffin wax, and less so in the shorter (but otherwise similar) mineral oil.
[0040] Apparently, the temporary dipole (+)------(-) in one molecule induces a dipole in the opposite direction (-)--------(+) in another molecule. This interaction occurs between the paraffin wax and other compounds within the composition. Thus, it may be concluded that molecular ranges within about C20-C40 have preferred capabilities in terms of stable breakable foam formation.
[0041] There seems to be another coinciding property of paraffin wax that may be involved with foam stability, which is its critical surface tension ("CST").
Hydrophobic behavior of surfaces is generally considered to occur when CST is less than 35 mN/m. At first, the decrease in critical surface tension is associated with oleophilic behavior, i.e. the wetting of the surfaces by hydrocarbon oils.
Hydrophobic behavior of surfaces is generally considered to occur when CST is less than 35 mN/m. At first, the decrease in critical surface tension is associated with oleophilic behavior, i.e. the wetting of the surfaces by hydrocarbon oils.
[0042] Paraffin wax is unique among other hydrocarbon chains by having a CST
of about 25 (e.g., 25.5), which is about in the middle of the hydrophobic range. Thus, paraffin waxes are somewhat amphipatic which may also contribute to foam stability. Notably, in comparison to longer hydrocarbons, such as polyethylene and polypropylene, paraffin wax is much more hydrophobic, thereby decreasing the surface tension of the hydrophobic solvents in the composition and facilitating foam formation and stabilization (the CST of polypropylene 31.0 and polyethylene 33.0).
of about 25 (e.g., 25.5), which is about in the middle of the hydrophobic range. Thus, paraffin waxes are somewhat amphipatic which may also contribute to foam stability. Notably, in comparison to longer hydrocarbons, such as polyethylene and polypropylene, paraffin wax is much more hydrophobic, thereby decreasing the surface tension of the hydrophobic solvents in the composition and facilitating foam formation and stabilization (the CST of polypropylene 31.0 and polyethylene 33.0).
[0043] The chain length amongst other things is responsible for the different melting points of the paraffin waxes. It was found that higher melting point paraffin waxes could form quality foams with less material than lower melting point fractions. Without being bound by any theory, it may be postulated that since high melting point fractions have longer chains, the Van der Vaals forces are greater so lower amounts can facilitate the formation of quality short term thermally stable foams. Thus, in an embodiment of the present invention, there is provided a paraffin wax, having CST of about 25; or between about 20 to about 30; or about 22 to about 28; about 23 to about 27; about 20 to about 30. In an embodiment selecting the CST of a wax is a means of providing a foamable formulation with a hydrophobic solvent that will generate a foam of quality that is at least short term stable.
[0044] Hydrogenated castor oil consists mainly of triglycerides of hydroxystearic acid and is a solid wax.
[0045] Beeswax contains, for example, a high proportion of wax esters (about 35 to 80%), which are linear monoesters of straight-chain fatty alcohols with even-numbered carbon chains from C24 to C36 esterified with straight-chain fatty acids such as 16:0 and 18:0 fatty acids some with hydroxyl groups in the w-2 and w-3 positions. The wax esters can consist of C40 to C46 molecular species, Also present are free acids (about 14%) and carbohydrates (about 12%) as well as approximately 1% free wax alcohols and stearic esters of fatty acids.
[0046] In one or more embodiments, the wax is a polyolefin such as polyethylene, polypropylene, polymethylpentene , polybutene, a polyolefin elastomer, polyisobutylene , ethylene propylene rubber, ethylene propylene diene Monomer (M-class) rubber, polyethylene terephthalate, polydicyclopentadiene, linear polyolefins, branched polyolefins, cyclic polyolefins, low density polyolefins, high density polyolefins, polyolefins with a low molecular weight, polyolefins with a high molecular weight, halogenated polyolefins and the like and mixture thereof.
[0047] In one or more embodiments, the wax is polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride, polyvinyl fluoride, polytetrafluoro ethylene, polychlorotrifluoro ethylene, polystyrene, polybutadiene, polyisoprene, polychloroprene, polymethylpentene and the like and mixture thereof.
[0048] In one or more certain embodiments a fatty alcohol and or a fatty acid may be added to the wax.
[0049] In one or more embodiments oily emollients are added to provide or improve a pleasant skin feeling, and or lubricating effect with reduced friction. In one or more embodiments volatile silicones are added to reduce greasy feeling. In one or more embodiments various waxes are added to improve rheology or stabilize foam structure.
[0050] Surfactants play a role in foam formation and induce foam stability. In one or more embodiments the formulation is substantially or essentially free of surfactants. In one or more embodiments a small amount of surfactant may be added, preferably less than I%. Scientific literature is not always accurate and may loosely or even inaccurately describe a substance as a surfactant. For example, fatty alcohols or fatty acids (in the absence of a base) when used in combination with classic surfactants have sometimes been referred to as surfactants, whereas at best they merely function as an aid to classic surfactant and may loosely be termed as a co-surfactant but they are not able to stabilize an emulsion and achieve a stable foam emulsion on their own without the presence of a true surfactant. (For more detail see "co-surfactant" below.) In the context of the present application such fatty acids and fatty alcohols are not surface active agents but are foam adjuvants. Similarly propoxylated lanolin oil derivatives have been loosely referred to as surfactants. In the context herein they are emollients (not surfactants). In one or more embodiments the composition is substantially free of foam adjuvants and comprises less than about 5% final concentration of foam adjuvants, preferably less than 2%, more preferably less than 1%. Where a formulation includes insignificant amounts of foam adjuvants it is considered to be essentially free of them. In one or more embodiments the composition is essentially free of foam adjuvants such as fatty alcohols and or fatty acids.
In one or more embodiments a small amount of foam adjuvant may be added, preferably less than I%. In one or more embodiments the composition is essentially free of propoxylated lanolin oil derivatives. In one or more embodiments the composition is essentially free of ethoxylated lanolin oil derivatives. In further embodiments the compositions are free of such derivatives. In one or more certain embodiments the composition is free of PPG, lanolin oils, such as PPG
40 PEG 60 lanolin oil. In one or more embodiments foam adjuvants (i.e. fatty alcohols and fatty acids) and additives (such as Si02 which acts as a thickener and can provide thixotropy) can be added to improve rheology or stabilize foam structure or as a protective agent. In one or more embodiments antioxidants can be used to prevent degradation /oxidation, for example, butylated hydroxytoluene, which is a fat soluble antioxidant.
In one or more embodiments a small amount of foam adjuvant may be added, preferably less than I%. In one or more embodiments the composition is essentially free of propoxylated lanolin oil derivatives. In one or more embodiments the composition is essentially free of ethoxylated lanolin oil derivatives. In further embodiments the compositions are free of such derivatives. In one or more certain embodiments the composition is free of PPG, lanolin oils, such as PPG
40 PEG 60 lanolin oil. In one or more embodiments foam adjuvants (i.e. fatty alcohols and fatty acids) and additives (such as Si02 which acts as a thickener and can provide thixotropy) can be added to improve rheology or stabilize foam structure or as a protective agent. In one or more embodiments antioxidants can be used to prevent degradation /oxidation, for example, butylated hydroxytoluene, which is a fat soluble antioxidant.
[0051] In one or more embodiments the foamable composition is substantially surfactant and foam adjuvant free. In one or more other embodiments it is essentially free of any surfactants and foam adjuvants.
[0052] Upon release from an aerosol container, the foamable composition forms an expanded breakable foam suitable for topical administration.
[0053] The foamable composition is suitable for administration to various body areas, including, but not limited to the skin, a body surface, a body cavity, a mucosal surface, e.g., the mucosa of the nose, mouth and eye, the ear, the respiratory system, the vagina or the rectum (severally and interchangeably termed herein "target site").
[0054] In one or more embodiments, the composition is waterless. By waterless is meant that the composition contains no or substantially no, free or unassociated or absorbed water. It will be understood by a person of the art that to the extent the waterless solvents and substances miscible within them of the present disclosure are hydrophilic, they can contain water in an associated or unfree or absorbed form and may absorb water from the atmosphere.
[0055] According to one or more embodiments, the foamable composition further comprises one or more cosmetic active agents or a pharmaceutical active agents (severally and interchangeably termed herein "active agent").
[0056] In one or more embodiments the carrier comprises an active agent which degrades in the presence of water, and in such cases the presence of water in the composition is clearly not desirable. Thus, in certain preferred embodiments, the composition is waterless. In other embodiments the active agent may tolerate the presence of a small amount of water and the waterless composition is substantially non-aqueous. The term "substantially non-aqueous" is intended to indicate that the waterless composition has water content preferably below about 2%, such as, below about 1.5%, below about 1%; or below about 0.5%. In certain embodiments the amount of water is about or less than about 5%. Where water is present the formulation may be an emulsion or may form micelles or a colloid.
[0057] In one or more embodiments there is provided a foamable therapeutic composition including:
1. an active agent;
2. a hydrophobic solvent between about 40% to about 92% by weight;
3. a foaming agent comprising between about 8% to about 50% by weight of wax;
4. a liquefied or compressed gas propellant wherein the percent by weight is based on weight foamable composition; wherein the ratio of composition other than propellant to propellant is from about 100:3 to about 100:30; and wherein upon dispensing the foamable carrier composition forms a breakable foam that is stable, yet breaks easily upon application of shear force.
1. an active agent;
2. a hydrophobic solvent between about 40% to about 92% by weight;
3. a foaming agent comprising between about 8% to about 50% by weight of wax;
4. a liquefied or compressed gas propellant wherein the percent by weight is based on weight foamable composition; wherein the ratio of composition other than propellant to propellant is from about 100:3 to about 100:30; and wherein upon dispensing the foamable carrier composition forms a breakable foam that is stable, yet breaks easily upon application of shear force.
[0058] In one or more embodiments the hydrophobic solvent range is between about 35% to about 95%; about 40% to about 95%; about 40% to about 92%; about 45% to about 92%; about 50% to about 92%; about 55% to about 92%; about 60% to about 92%; about 40% to about 90%;
about 45% to about 90%; about 50% to about 90%; about 55% to about 90%; about 60% to about 90%; about 40% to about 85%; about 45% to about 85%; about 50% to about 85%;
about 55% to about 85%; about 60% to about 85% about 40% to about 80%; about 45% to about 80%; about 50% to about 80%; about 55% to about 80%; about 60% to about 80%; about 40% to about 70%;
about 45% to about 70%; about 50% to about 70%; about 55% to about 70%; or about 60% to about 70%
about 45% to about 90%; about 50% to about 90%; about 55% to about 90%; about 60% to about 90%; about 40% to about 85%; about 45% to about 85%; about 50% to about 85%;
about 55% to about 85%; about 60% to about 85% about 40% to about 80%; about 45% to about 80%; about 50% to about 80%; about 55% to about 80%; about 60% to about 80%; about 40% to about 70%;
about 45% to about 70%; about 50% to about 70%; about 55% to about 70%; or about 60% to about 70%
[0059] In one or more embodiments the wax range is between about 5% to about 52%; about 8% to about 52%; about 10% to about 52%; about 15% to about 52%; about 20% to about 52%;
about 25% to about 52%; about 30% to about 52%; 5% to about 50%; about 8% to about 50%;
about 10% to about 50%; about 15% to about 50%; about 20% to about 50%; about 25% to about 50%; about 30% to about 50%; 5% to about 45%; about 8% to about 45%; about 10%
to about 45%; about 15% to about 45%; about 20% to about 45%; about 25% to about 45%;
or about 30%
to about 45%; 5% to about 40%; about 8% to about 40%; about 10% to about 40%;
about 15% to about 40%; about 20% to about 40%; about 25% to about 40%; or about 30% to about 40%;
about 25% to about 52%; about 30% to about 52%; 5% to about 50%; about 8% to about 50%;
about 10% to about 50%; about 15% to about 50%; about 20% to about 50%; about 25% to about 50%; about 30% to about 50%; 5% to about 45%; about 8% to about 45%; about 10%
to about 45%; about 15% to about 45%; about 20% to about 45%; about 25% to about 45%;
or about 30%
to about 45%; 5% to about 40%; about 8% to about 40%; about 10% to about 40%;
about 15% to about 40%; about 20% to about 40%; about 25% to about 40%; or about 30% to about 40%;
[0060] In one or more embodiments, at least a portion of the therapeutic agent is suspended.
In one or more embodiments the therapeutic agent is dissolved. In one or more embodiments it is partly suspended and partly dissolved. In one or more embodiments the suspended agent is evenly or homogenously distributed throughout the composition. In one or more embodiments homogeneity is achieved after shaking shortly before intended use.
In one or more embodiments the therapeutic agent is dissolved. In one or more embodiments it is partly suspended and partly dissolved. In one or more embodiments the suspended agent is evenly or homogenously distributed throughout the composition. In one or more embodiments homogeneity is achieved after shaking shortly before intended use.
[0061] Formulations containing high amounts of hydrophobic solvents (such as mineral oil) are not prone to foaming. For example, it has been found that a formulation containing only mineral oil and propellants did not produce foam.. Similarly, formulations containing paraffin wax and propellant only did not produce foam. It has also been found that when a propellant is added to combinations of one or more different oils with relatively low levels of one or more different waxes in the absensce of foam stabilizers such as surfactants or foam adjuvants, foams were mostly not produced at all or were not of quality and collapsed rapidly.
In other words they were not short term stable and breakable quality foams.
In other words they were not short term stable and breakable quality foams.
[0062] Suprisingly, when propellant was added to formualtions containing a combination of certain hydrophobic solvents and waxes, preferably parafin wax, together having a total weight of about 100% or about 95% , short term stable yet breakable quality foams were succesfully produced in the absence of customary surfactants and in the absence of customary foam adjuvants. Thus, unexpectedly it was discovered that wax has foaming or foam boosting properties of its own when formulated with hydrophobic solvents, such as mineral oil, and provides breakable short stable foams of good quality. The amount of wax required depends on the type of wax selected. In general, the amounts of parafin waxes having a higher melting point range needed to achieve a good quality foam can be less than the amounts of parafin waxes having a lower melting point range. Moreover, in general, higher amounts of hydrogenated caster oil wax or beeswax are needed to achieve a foam compared to parafin wax.
Similarly, higher amounts of beeswax are needed to achieve a foam compared to hydrogenated caster oil wax
Similarly, higher amounts of beeswax are needed to achieve a foam compared to hydrogenated caster oil wax
[0063] For example, formulations containing between about 50% and about 90%
heavy mineral oil and from about 10% to about 50% paraffin wax (having a melting point of about 51-53 C) produced good to excellent quality foams that had a collapse time of about more than 2 minutes or about more than 3 minutes at 36 C. Excellent foams that were stable for more than 3 minutes were obtained in formulations having from about 15% to about 50%paraffin wax 51-53 C. On the other hand formulations with paraffin wax 51-53 C, 5% produced poor foam whilst 7.5% generated only fairly good foam.
heavy mineral oil and from about 10% to about 50% paraffin wax (having a melting point of about 51-53 C) produced good to excellent quality foams that had a collapse time of about more than 2 minutes or about more than 3 minutes at 36 C. Excellent foams that were stable for more than 3 minutes were obtained in formulations having from about 15% to about 50%paraffin wax 51-53 C. On the other hand formulations with paraffin wax 51-53 C, 5% produced poor foam whilst 7.5% generated only fairly good foam.
[0064] Also formulations containing about 60% heavy or light mineral oil and about 40%
paraffin wax (having a melting point of about 42-44 C) produced excellent quality foams that displayed a collapse time of about or more than 1 minute or more than 2 minutes at 36 C
depending on the propellant. On the other hand formulations with 20% of 42-44 resulted in a poor quality.
paraffin wax (having a melting point of about 42-44 C) produced excellent quality foams that displayed a collapse time of about or more than 1 minute or more than 2 minutes at 36 C
depending on the propellant. On the other hand formulations with 20% of 42-44 resulted in a poor quality.
[0065] In an embodiment foam quality may be improved by increasing the propellant, by say aliqots of 2% or 4%, for example, from 8% to about 12%. The actual amount of propellant increase that is suitable should be titrated from formulation to formulation.
[0066] Furthermore, formulations containing between about 80% and about 90%
heavy mineral oil and between about 10% and about 20% paraffin wax (having a melting point of about 58-62 C) produced excellent quality foams, having low density (between 0.land 0.2g/mL) that exhibited a collapse time of about or more than 3 minutes at 36 C.
heavy mineral oil and between about 10% and about 20% paraffin wax (having a melting point of about 58-62 C) produced excellent quality foams, having low density (between 0.land 0.2g/mL) that exhibited a collapse time of about or more than 3 minutes at 36 C.
[0067] Furthermore, different oleaginous foam formulation consisting of 80% of various oils and 20% paraffin wax (51-53 C),or consisting of 80% heavy mineral oil and 20%
paraffin wax (51-53 C) and various propellants or consisting of heavy mineral oil between about 60%-80%
and various waxes between about 20%-40% produced quality foams that showed a collapse time of about or more than 2 minutes or more than 3 minutes at 36 C.
paraffin wax (51-53 C) and various propellants or consisting of heavy mineral oil between about 60%-80%
and various waxes between about 20%-40% produced quality foams that showed a collapse time of about or more than 2 minutes or more than 3 minutes at 36 C.
[0068] Furthermore, oleaginous foam formulation consisting of 80% heavy mineral oil and 20% paraffin wax (51-53 C) showed physical stability in accelerated stability tests. There was hardly any change in foam quality, density or collapse time after 2 months of storage at 40 C. A
decrease in formulation shakability was detected which may be explained by a partial solidification of the wax content with time. It may be overcome inter alia by increasing the propellant concentration of the formulation to about 12%, or by using a propellant having a higher vapor pressure such as propellant comprising propane.
decrease in formulation shakability was detected which may be explained by a partial solidification of the wax content with time. It may be overcome inter alia by increasing the propellant concentration of the formulation to about 12%, or by using a propellant having a higher vapor pressure such as propellant comprising propane.
[0069] These results were surprising as no known foam stabilizing agent such as surfactants was present. Moreover, no fatty alcohol or fatty acid was needed, and formulations containing only hydorphobic solvents and waxes generated thermally stable quality foams.
[0070] It has further been found that for high concentrations of wax, the inclusion of higher amounts of propellant was found useful in order to improve the flowability of the formulation within the canister, as indicated by the shakability results.
[0071] In one or more embodiments there is provided a foamable carrier composition comprising a solvent, a wax and a liquefied or compressed gas propellant wherein the formulation provides upon dispensing a breakable foam of quality which has a collapse time at 36 C of about or more than 1 minute. In one or more embodiments, the solvent is a hydrophobic solvent. In one or more embodiments, the hydrophobic solvent is mineral oil.
In one or more embodiments, the wax is a paraffin wax. In one or more embodiments, the wax is a hydrogenated caster oil. In one or more embodiments, the wax is a beeswax.
In one or more embodiments, the wax is a paraffin wax. In one or more embodiments, the wax is a hydrogenated caster oil. In one or more embodiments, the wax is a beeswax.
[0072] In one or more embodiments there is provided a foamable carrier composition comprising a hydrophobic solvent between about 50% to about 90% by weight of formulation, a wax between about 10% to about 50% by weight of formulation and a liquefied or compressed gas propellant wherein the formulation provides upon dispensing a breakable foam of quality which has a collapse time at 36 C of about or more than 1 minute. In one or more embodiments the composition further comprises one or more active agents.
[0073] In one or more embodiments there is provided a foamable carrier composition comprising a solvent selected from a list consisting of a capric/caprylic triglycerides, PPG- 15 stearyl ether, isopropyl palmitate, isopropyl myristate, octyldodecanol, between about 50% to about 90% by weight of formulation, wax between about 10% to about 50% by weight of formulation and a liquefied or compressed gas propellant wherein the formulation provides upon dispensing a breakable foam of quality which has a collapse time at 36 C of about or more than 1 minute. In one or more embodiments the composition further comprises one or more active agents.
[0074] In one or more embodiments there is provided a foamable carrier composition comprising a hydrophobic solvent between about 50% to about 90% by weight of formulation, wax between about 10% to about 50% by weight of formulation and a liquefied or compressed gas propellant where the propellant is hydrocarbon or hydrofluorocarbon propellant which may selected from a the group consisting of propane, butane, isobutene or mixtures of two or three thereof, AP-70, A-46, Dymel 134a or mixtures of two or more thereof, wherein the formulation provides upon dispensing a breakable foam of quality with a collapse time at 36 C of about or more than 1 minute. In one or more embodiments the composition further comprises one or more active agents.
[0075] In one or more embodiments inclusion of higher amounts of propellant improves the flowability of the formulation. In one or more embodiments the improvement is more pronounced where there are high amounts of waxes within the canister.
[0076] Furthermore, the formulations of the present invention comprising a hydrophobic solvent, for example, mineral oil, and a wax, for example, a paraffin wax 51-53 C, and a propellant in an effective amount can provide foams of good quality in the presence of various active ingredients. In the context herein active pharmaceutical ingredients and active cosmetic ingredients are collectively termed "active agent" or "active agents".
Formulations, for example, comprising minocycline HC1, mometasone fuorate, calcitriol and lidocaine produced breakable foams of quality which are stable and have a collapse time at 36 C of about or more than 1 minute.
Formulations, for example, comprising minocycline HC1, mometasone fuorate, calcitriol and lidocaine produced breakable foams of quality which are stable and have a collapse time at 36 C of about or more than 1 minute.
[0077] In one or more embodiments there is provided a foamable carrier composition comprising a solvent, a wax and a liquefied or compressed gas propellant and one or more active ingredients wherein the formulation provides upon dispensing a breakable foam of quality which has a collapse time at 36 C of about more than 1 minute. In one or more embodiments, the solvent is a hydrophobic solvent. In one or more embodiments, the hydrophobic solvent is mineral oil. In one or more embodiments, the wax is a paraffin wax. In one or more embodiments, the wax is a hydrogenated caster oil. In one or more embodiments, the wax is a beeswax.
[0078] In one or more embodiments, the active agent is a tetracycline. In one or more embodiments, the tetracycline active agent is a minocycline HC1. In one or more embodiments, the active agent is a benzoyl peroxide. In one or more embodiments, the active agent is mometasone fuorate. In one or more embodiments, the active agent is calcitriol or another vitamin D derivative. In one or more embodiments, the active agent is lidocaine.
[0079] In one or more embodiments, the composition is essentially free of polyols.
[0080] In one or more embodiments, composition is capable of providing intradermal delivery of the active agent into the skin with minimal or negligible transdermal delivery.
[0081] In one or more embodiments, the composition is for use in eye infections.
[0082] In one or more embodiments, the composition is physically stable for at least two months.
[0083] In one or more embodiments, there is provided a substantially surfactant and foam adjuvant free composition comprising:
a) about 50% to about 90% by weight of a hydrophobic solvent;
b) an oleaginous foaming agent comprising i) about 10% to about 50% by weight of paraffin wax;
c) an active agent, d) a liquefied or compressed gas propellant wherein the percent by weight is based on weight of foamable composition;
wherein the ratio of composition other than propellant to propellant is from about 100:3 to about 100:30;
wherein upon dispensing the foamable carrier composition forms a breakable foam that is stable, yet breaks easily upon application of shear force, and wherein the active agent is compatible with in the formulation; wherein the formulation provides upon dispensing a breakable foam of quality which has a collapse time at 36 C of about more than 1 minute.
a) about 50% to about 90% by weight of a hydrophobic solvent;
b) an oleaginous foaming agent comprising i) about 10% to about 50% by weight of paraffin wax;
c) an active agent, d) a liquefied or compressed gas propellant wherein the percent by weight is based on weight of foamable composition;
wherein the ratio of composition other than propellant to propellant is from about 100:3 to about 100:30;
wherein upon dispensing the foamable carrier composition forms a breakable foam that is stable, yet breaks easily upon application of shear force, and wherein the active agent is compatible with in the formulation; wherein the formulation provides upon dispensing a breakable foam of quality which has a collapse time at 36 C of about more than 1 minute.
[0084] It was observed that when a more solid paraffin wax was used the stabilty of the formualtion was improved yet shakability decreased (compare samples 023, 024 to samples 031, 032 respectively and also compare samples 035 to sample 013 respectively). It was also observed that the when light mineral oil was used as opposed to heavy mineral oil the shakability was improved (compare samples 029, 030 to samples 023, 024 respectively). It may be, without being bound by any theory, that apart from any other chemical differences between the different waxes, the observations may be accounted for in part or entitrity by the longer wax chain lengths in the higher melting point parafin waxes.
Hydrophobic Solvent
Hydrophobic Solvent
[0085] In an embodiment, the composition of the present invention comprises at least one hydrophobic organic solvent. A "hydrophobic organic solvent" (also termed "hydrophobic solvent") as used herein refers to a material having solubility in distilled water at ambient temperature of less than about 1 gm per 100 mL, more preferably less than about 0.5 gm per 100 mL, and most preferably less than about 0.1 gm per 100 mL. It is liquid at ambient temperature.
The identification of a "hydrophobic solvent", as used herein, is not intended to characterize the solubilization capabilities of the solvent for any specific active agent or any other component of the foamable composition. Rather, such term is provided to aid in the identification of materials suitable for use as a hydrophobic solvent in the foamable compositions described herein.
The identification of a "hydrophobic solvent", as used herein, is not intended to characterize the solubilization capabilities of the solvent for any specific active agent or any other component of the foamable composition. Rather, such term is provided to aid in the identification of materials suitable for use as a hydrophobic solvent in the foamable compositions described herein.
[0086] In one or more embodiments the hydrophobic solvent is present at a concentration of about 40% to about 90%; or about 50% to about 95%; or about 60% to about 95%
or about 65%
to about 90%; or about 70% to about 90% or about 75% to about 85%.
or about 65%
to about 90%; or about 70% to about 90% or about 75% to about 85%.
[0087] In one or more embodiments, the composition of the present invention comprises at least one hydrophobic solvent, selected from the group consisting of a mineral oil, a hydrocarbon oil, an ester oil, a liquid triglyceride oil, an oil of plant origin, an oil from animal origin, an unsaturated or polyunsaturated oil, a diglyceride, a PPG alkyl ether and a silicone oil.
[0088] As exemplified herein, members of each of the above listed groups of hydrophobic solvents have been found to be compatible with hydrophobic tetracyclines, such as minocycline and doxycycline.
[0089] Non-limiting examples of hydrocarbon oils include mineral oil, liquid paraffin, an isoparaffin, a polyalphaolefin, a polyolefin, polyisobutylene, a synthetic isoalkane, isohexadecane and isododecane.
[0090] Non-limiting examples of ester oils include alkyl benzoate, alkyl octanoate, C12-C15 alkyl benzoate, C l2-C 15 alkyl octanoate, arachidyl behenate, arachidyl propionate, benzyl laurate, benzyl myristate, benzyl palmitate, bis (octyldodecyl stearoyl) dimer dilinoleate, butyl myristate, butyl stearate, cetearyl ethylhexanoate, cetearyl isononanoate, cetyl acetate, cetyl ethylhexanoate, cetyl lactate, cetyl myristate, cetyl octanoate, cetyl palmitate, cetyl ricinoleate, decyl oleate, diethyleneglycol diethylhexanoate, diethyleneglycol dioctanoate, diethyleneglycol diisononanoate, diethyleneglycol diisononanoate, diethylhexanoate, diethylhexyl adipate, diethylhexyl malate, diethylhexyl succinate, diisopropyl adipate, diisopropyl dimerate, diisopropyl sebacate, diisosteary dimer dilinoleate, diisostearyl fumerate, dioctyl malate, dioctyl sebacate, dodecyl oleate, ethylhexyl palmitate, ester derivatives of lanolic acid, ethylhexyl cocoate, ethylhexyl ethylhexanoate, ethylhexyl hydroxystarate, ethylhexyl isononanoate, ethylhexyl palmytate, ethylhexyl pelargonate, ethylhexyl stearate, hexadecyl stearate, hexyl laurate, isoamyl laurate, isocetyl isocetyl behenate, isocetyl lanolate, isocetyl palmitate, isocetyl stearate, isocetyl salicylate, isocetyl stearate, isocetyl stearoyl stearate, isocetearyl octanoate, isodecyl ethylhexanoate, isodecyl isononanoate, isodecyl oleate, isononyl isononanoate, isodecyl oleate, isohexyl decanoate, isononyl octanoate, isopropyl isostearate, isopropyl lanolate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearyl behenate, isosteary citrate, isostearyl erucate, isostearyl glycolate, isostearyl isononanoate, isostearyl isostearate, isostearyl lactate, isostearyl linoleate, isostearyl linolenate, isostearyl malate, isostearyl neopentanoate, isostearyl palmitate, isosteary salicylate, isosteary tartarate, isotridecyl isononanoate, isotridecyl isononanoate, lauryl lactate, myristyl lactate, myristyl myristate, myristyl neopentanoate, myristyl propionate, octyldodecyl myristate, neopentylglycol dicaprate, octyl dodecanol, octyl stearate, octyl palmitate, octyldodecyl behenate, octyldodecyl hydroxystearate, octyldodecyl myristate, octyldodecyl stearoyl stearate, oleyl erucate, oleyl lactate, oleyl oleate, propyl myristate, propylene glycol myristyl ether acetate, propylene glycol dicaprate, propylene glycol dicaprylate, propylene glycol dicaprylate, maleated soybean oil, stearyl caprate, stearyl heptanoate, stearyl propionate, tocopheryl acetate, tocopheryl linoleate, glyceryl oleate, tridecyl ethylhexanoate, tridecyl isononanoate and triisocetyl citrate.
[0091] Non-limiting examples of liquid triglycerides and oils of plant origin include alexandria laurel tree oil, avocado oil, apricot stone oil, barley oil, borage seed oil, calendula oil, canelle nut tree oil, canola oil, caprylic/capric triglyceride castor oil, coconut oil, corn oil, cotton oil, cottonseed oil, evening primrose oil, flaxseed oil, groundnut oil, hazelnut oil, glycereth triacetate, glycerol triheptanoate, glyceryl trioctanoate, glyceryl triundecanoate, hempseed oil, jojoba oil, lucerne oil, maize germ oil, marrow oil, millet oil, neopentylglycol dicaprylate/dicaprate, olive oil, palm oil, passionflower oil, pentaerythrityl tetrastearate, poppy oil, propylene glycol ricinoleate, rapeseed oil, rye oil, safflower oil, sesame oil, shea butter, soya oil, soybean oil, sweet almond oil, sunflower oil, sysymbrium oil, syzigium aromaticum oil, tea tree oil, walnut oil, wheat germ glycerides and wheat germ oil.
[0092] Non-limiting examples of PPG alkyl ethers include PPG-2 butyl ether, PPG-4 butyl ether, PPG-5 butyl ether, PPG-9 butyl ether, PPG-12 butyl ether, PPG-14 butyl ether, PPG-15 butyl ether, PPG- 15 stearyl ether, PPG- 16 butyl ether, PPG- 17 butyl ether, PPG- 18 butyl ether, PPG-20 butyl ether, PPG-22 butyl ether, PPG-24 butyl ether, PPG-26 butyl ether, PPG-30 butyl ether, PPG-33 butyl ether, PPG-40 butyl ether, PPG-52 butyl ether, PPG-53 butyl ether, PPG-10 cetyl ether, PPG-28 cetyl ether, PPG-30 cetyl ether, PPG-50 cetyl ether, PPG-30 isocetyl ether, PPG-4 lauryl ether, PPG-7 lauryl ether, PPG-2 methyl ether, PPG-3 methyl ether, PPG-3 myristyl ether, PPG-4 myristyl ether, PPG-10 oleyl ether, PPG-20 oleyl ether, PPG-23 oleyl ether, PPG-30 oleyl ether, PPG-37 oleyl ether, PPG-40 butyl ether, PPG-50 oleyl ether and PPG-11 stearyl ether. Preferred PPG alky ethers according to the present invention include PPG- 15 stearyl ether, PPG-2 butyl ether and PPG-9-13 butyl ether.
[0093] Non-limiting examples of oils from animal origin include herring oil, cod-liver oil and salmon oil.
[0094] The hydrophobic solvent may be an emollient, i.e., a hydrophobic liquid having a softening or soothing effect especially to the skin. In some embodiments the liquid oil may contain a solid or semi solid hydrophobic matter at room temperature.
[0095] Essential oil, which is usually a concentrated, hydrophobic liquid containing volatile aroma compounds from plants usually conveying characteristic fragrances. Non limiting examples include lavender, peppermint, and eucalyptus. A therapeutic oil is a hydrophobic liquid which is said to have a therapeutic effect or to have associated with it certain healing properties.
Therapeutic oils contain active biologically occurring molecules and, upon topical application, exert a therapeutic effect. Non limiting examples include manuka oil, rosehip oil, which contains retinoids and is known to reduce acne and post-acne scars, and tea tree oil, which possesses anti-microbial activity including antibacterial, antifungal and antiviral properties as well as any other therapeutically beneficial oil known in the art of herbal medication. Many essential oils are considered "therapeutic oils." Other non limiting examples of essential oils are basil, camphor, cardamom, carrot, citronella, Clary sage, clove, cypress, frankincense, ginger, grapefruit, hyssop, jasmine, lavender, lemon, mandarin, marjoram, myrrh, neroli, nutmeg, petitgrain, sage, tangerine, vanilla and verbena.
Therapeutic oils contain active biologically occurring molecules and, upon topical application, exert a therapeutic effect. Non limiting examples include manuka oil, rosehip oil, which contains retinoids and is known to reduce acne and post-acne scars, and tea tree oil, which possesses anti-microbial activity including antibacterial, antifungal and antiviral properties as well as any other therapeutically beneficial oil known in the art of herbal medication. Many essential oils are considered "therapeutic oils." Other non limiting examples of essential oils are basil, camphor, cardamom, carrot, citronella, Clary sage, clove, cypress, frankincense, ginger, grapefruit, hyssop, jasmine, lavender, lemon, mandarin, marjoram, myrrh, neroli, nutmeg, petitgrain, sage, tangerine, vanilla and verbena.
[0096] Some embodiments include silicone oils. Non-limiting examples of silicone oils include a cyclomethicone, dimethicone, a polyalkyl siloxane, a polyaryl siloxane, a polyalkylaryl siloxane, a polyether siloxane copolymer, a poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer, a dimethyl polysiloxane, an epoxy-modified silicone oil, a fatty acid-modified silicone oil, a fluoro group-modified silicone oil, a methylphenylpolysiloxane, phenyl trimethicone and a polyether group-modified silicone oil. In some embodiments, the silicone oil is cyclomethicone, cyclotetrasiloxane, cyclohexasiloxane, phyenyltrimethicone, Dow coming 246 Fluid (d6+d5) (cyclohexasiloxane & cyclopentasiloxane), Dow Coming 244 Fluid (cyclotetrasiloxane), Cyclomethicone 5-NF (cyclopentasiloxane), stearyl dimethicone, phenyltrimethicone, cetyl dimethicone, caprylyl methicone, PEG/PPG 18/18 dimethicone, or dimethiconol.
[0097] In one or more embodiments, the hydrophobic solvent may be selected from capric/caprylic triglycerides, cyclomethicone; isopropyl myristate, isopropyl palmitate, PPG- 15 stearyl ether; octyldodecanol; isohexadecanol, diisopropyl adipate; cetearyl octanoate; ; MCT
oil; heavy mineral oil; light mineral oil; coconut oil and soybean oil.
oil; heavy mineral oil; light mineral oil; coconut oil and soybean oil.
[0098] Mixtures of two or more hydrophobic solvents in the same foamable composition is contemplated. Furthermore, in certain embodiments, the use of mixtures of two or more hydrophobic solvents is preferred.
[0099] Yet, in certain embodiments, the hydrophobic solvent is a mixture of one or more liquid hydrophobic solvents, as listed above, together with an additional hydrophobic substance, which is not liquid (such as petrolatum), provided that the resultant mixture of all hydrophobic substances, is liquid at ambient temperature. In an embodiment the resultant mixture upon including propellant is liquid at ambient temperature. In certain embodiments the main hydrophobic substance in the formulation is a petrolatum, which is a semi solid, in combination with at least one liquid hydrophobic solvent. For example petrolatum may be added to provide a degree of occlusivity so that the formulation when applied to a skin surface can operate to increase skin moisture and or reduced transdermal water loss. In certain other embodiments a liquid hydrophobic solvent is not added. Fluidity of the composition can be achieved by utilizing liquidizing solvents (e.g. C12 C15 Alkyl benzoate) and or liquefied propellants and or optionally liquid adjuvants. Inclusion of higher amounts of propellant was found useful in order to improve flowability of the formulation from the canister or by using propellants having a higher vapor pressure.
Fatty Alcohol
Fatty Alcohol
[0100] If at all present, the fatty alcohol is selected from the group consisting of fatty alcohols having 15 or more carbons in their carbon chain, such as cetyl alcohol and stearyl alcohol (or mixtures thereof). Other examples of fatty alcohols are arachidyl alcohol (C20), behenyl alcohol (C22), tetracosanol, hexacosanol, octacosanol, triacontanol, tetratriacontanol, 1-triacontanol (C30), as well as alcohols with longer carbon chains (up to C50).
In one or more other embodiments, the fatty alcohol is selected from the group consisting of fatty alcohols having 14 or less carbons in their carbon chain, such as lauryl alcohol and myristyl alcohol. In an embodiment the fatty alcohol is a solid at room temperature.
In one or more other embodiments, the fatty alcohol is selected from the group consisting of fatty alcohols having 14 or less carbons in their carbon chain, such as lauryl alcohol and myristyl alcohol. In an embodiment the fatty alcohol is a solid at room temperature.
[0101] Fatty Acid
[0102] If at all present the fatty acid can have 16 or more carbons in its carbon chain, such as hexadecanoic acid (C 16), heptadecanoic acid, stearic acid (C 18), arachidic acid (C20), behenic acid (C22), tetracosanoic acid (C24), hexacosanoic acid (C26, heptacosanoic acid (C27), octacosanoic acid (C28), triacontanoic acid, dotriacontanoic acid, tritriacontanoic acid, tetratriacontanoic acid and pentatriacontanoic acid. as well as fatty acids with longer carbon chains (up to C50), or mixtures thereof. In one or more other embodiments, the fatty acid is selected from the group consisting of fatty alcohols having 14 or less carbons in their carbon chain, such as dodecanoic acid, myristic acid, myristoleic acid, and lauric acid. In an embodiment the fatty acid is a solid at room temperature.
Waxes
Waxes
[0103] The foaming agent includes a wax. The wax which usually acts as a type of foam adjuvant is included in the foamable compositions to evolve the foaming property of the composition and/or to stabilize the foam. Wax refers to paraffin wax or beeswax or hydrogenated castor oil or another substance with similar properties. The term wax refers to a class of substances with properties similar to beeswax, in respect of (i) plastic behavior at normal ambient temperatures, a melting point above approximately 45 C, (ii) a relatively low viscosity when melted (unlike many plastics); and (iii) hydrophobic nature. Suitable exemplary waxes which can be incorporated into the formulation include animal, vegetable, mineral or silicone based waxes which may be natural or synthetic such as, for example: beeswax, Chinese wax, lanolin (wool wax), shellac wax, bayberry wax, candelilla wax, camauba wax, castor wax, esparto wax, japan wax, ouricury wax, rice bran wax, soy wax, hydrogenated oil such ashydrogenated castor oil, hydrogenated cottonseed oil, or hydrogenated jojoba oil, mink wax, motan wax, ouricury wax, ozokerite, PEG-6 beeswax, rezowax, spent grain wax, stearyl dimethicone, paraffin waxes, such as paraffin 42-44, 51-53 58-62 wax, and the like and mixtures thereof. In one or more embodiments the wax is selected from a list comprising of a solid wax, an animal wax, a vegetable wax, a mineral wax, a natural wax or a synthetic wax. In certain embodiments the term wax can extend to hydrogenated oils. In one or more preferred embodiments, the wax is a beeswax or hydrogenated castor oil.
[0104] In one or more embodiments the range of ratio of wax/ hydrophobic solvent can be about 100:1 to about 1:100; or about 90:1 to about 1:45; or about 80:1 to about 1:40; or about 70:1 to about 1:35; or about 60:1 to about 1:30; or about 50:1 to about 1:25;
or about 40:1 to about 1:20; or about 30:1 to about 1:15; or about 20:1 to about 1:10; or about 15:1 to about 1:5;
or about 10:1 to about 1:1; or any ranges in between such as 1:20 to 20:1, or preferably from 1:15 to 15:1. Preferably the range of the ratio of wax/ hydrophobic solvent can be selected from a list comprising of : about 1:10; about 10:1; about 1:9 to about 9:1; or about 1:7 to about 7:l;or about 3:17 to about 17:3; or about 1:4 to about 4:1; or about 1:3 to about 3:1; or about 2:5 to about 5:2;
or about 3:7 to about 7:3; or about 1:2 to about 2:1; or about 5:9 to about 9:5; or about 2:3 to about 3:2; or about 9:11 to about 11:9;
or about 40:1 to about 1:20; or about 30:1 to about 1:15; or about 20:1 to about 1:10; or about 15:1 to about 1:5;
or about 10:1 to about 1:1; or any ranges in between such as 1:20 to 20:1, or preferably from 1:15 to 15:1. Preferably the range of the ratio of wax/ hydrophobic solvent can be selected from a list comprising of : about 1:10; about 10:1; about 1:9 to about 9:1; or about 1:7 to about 7:l;or about 3:17 to about 17:3; or about 1:4 to about 4:1; or about 1:3 to about 3:1; or about 2:5 to about 5:2;
or about 3:7 to about 7:3; or about 1:2 to about 2:1; or about 5:9 to about 9:5; or about 2:3 to about 3:2; or about 9:11 to about 11:9;
[0105] In one or more embodiments Shea butter may be further added to the composition.
Shea butter may, for example, be used in addition to paraffin wax or bees wax or hydrogenated caster oil in order to enhance foam quality or to complement the action of one or more of them.
Shea butter may, for example, be used in addition to paraffin wax or bees wax or hydrogenated caster oil in order to enhance foam quality or to complement the action of one or more of them.
[0106] In one or more embodiments the foaming agent can further include be a fatty alcohol and shea butter, or a fatty acid and shea butter or a combination of a fatty alcohol and a fatty acid and shea butter.
Propellant
Propellant
[0107] The composition requires the addition of a propellant in order to generate a foam.
[0108] Suitable propellants include volatile hydrocarbons such as butane, propane, isobutene or mixtures thereof. In one or more embodiments a hydrocarbon mixture AP-70 is used. In one or more other embodiments a lower pressure hydrocarbon mixture AP-46 is used.
Both contain butane, propane, isobutene although in different proportions. AP-70 is composed of about 50%
w/w of propane, about 20% w/w of isobutane and about 30% w/w of propane. AP-46 is composed of about 16% w/w of propane, about 82% w/w of isobutane and about 2%
w/w of propane. Hydro fluorocarbon (HFC) propellants are also suitable as propellants in the context disclosed herein. Exemplary HFC propellants include 1,1,1,2 tetrafluorethane (Dymel 134), and 1,1,1,2,3,3,3 heptafluoropropane (Dymel 227). Dimethyl ether is also useful.
In one or more embodiments use of compressed gases (e.g., air, carbon dioxide, nitrous oxide, and nitrogen) is also possible.
Both contain butane, propane, isobutene although in different proportions. AP-70 is composed of about 50%
w/w of propane, about 20% w/w of isobutane and about 30% w/w of propane. AP-46 is composed of about 16% w/w of propane, about 82% w/w of isobutane and about 2%
w/w of propane. Hydro fluorocarbon (HFC) propellants are also suitable as propellants in the context disclosed herein. Exemplary HFC propellants include 1,1,1,2 tetrafluorethane (Dymel 134), and 1,1,1,2,3,3,3 heptafluoropropane (Dymel 227). Dimethyl ether is also useful.
In one or more embodiments use of compressed gases (e.g., air, carbon dioxide, nitrous oxide, and nitrogen) is also possible.
[0109] In one or more embodiments a combination of at least two propellants, selected from HFC, hydrocarbon propellants, dimethyl ether and compressed gases is contemplated.
[0110] Yet, in additional embodiments, the propellant is a self-foaming propellant, i.e., a volatile liquid having a boiling point of less than the temperature of the target treatment site (such as the skin). An example of a post-foaming propellant is isopentane (bp=26 C)
[0111] Any concentration of the propellant, which affords an acceptable foam, is useful in accordance with the present invention. In certain embodiments the propellant makes up between about 1% and about 30% of the foamable composition, or about 3% and 25%; and in certain preferred embodiments between about 5% and about 16% of the composition. In preparing the formulations the ingredients other than propellant are combined to 100% and the propellant is added thereafter so that the ratio of formulation to propellant can range from 100:1 to 100:30 100:4 to 100:25 or preferably 100:5 to 100:16. Yet, in additional embodiments, the ratio of composition other than propellant to propellant is between about 100:20 and about 100:50.
[0112] Due to environmental concerns, as well as compatibility considerations, propellants that are not environmentally friendly are in one or more embodiments to be avoided. So chlorofluoro carbons (CFC's), which are known to damage the ozone layer in the atmosphere, are essentially excluded from the formulations.
[0113] In one or more embodiments, the propellant can also be used to expel formulation using a bag in can system or a can in can system as will be appreciated by someone skilled in the art. In certain embodiments the part of the propellant system is in the formulation and part separate from the formulation. In this way it is possible to reduce the amount of surfactant in the formulation but still provide good expulsion from the canister, where the foamable formulation is expelled quickly but without jetting or noise.
[0114] In one or more embodiments a foam formulation is expelled from a standard pressurized canister where the propellant is part of formulation. Formulations can be expelled or helped to be expelled by using propellant which is separate from the formulation using a bag in can or can in can system. Although, these systems can be used with compressed air the pressure may not be sufficient to expel the formulation through the device and higher pressure propellant such as AP70 should be selected. In one or more embodiments, the formulation is packaged in bag in can systems or in can in can system. In one or more embodiments, the formulation is expelled from the canister using the pressure provided by the propellant mixed with the formulation. In one or more embodiments, the formulation is expelled from the canister using the pressure provided by the propellant stored in a compartment surrounding the formulation.
According to other embodiments part of the propellant system is in the formulation and part of the propellant system is separate from the formulation, which is used to expel said formulation using a bag or can in can system. In this way it is possible to reduce the amount of propellant within the formulation and avoid unwanted gaseous effects, for example in vaginal applications, but still provide good expulsion from the canister, where the foamable formulation is expelled sufficiently quickly but without jetting or noise. So by way of example, between about 1% to 3%;
or between about 2% to 4%; between about 3% to 5% propellant (ratio of formulation to propellant of 100: 1 to 3; 100: 2 to 4; 100: 3 to 5; respectively) is part of the formulation and a further amount of propellant is separate form the formulation and helps expel the formulation. In one or more embodiments a similar amount of propellant is in the formulation and a pump or other mechanical means is used to provide the additional expulsion force.
Modulating Agent
According to other embodiments part of the propellant system is in the formulation and part of the propellant system is separate from the formulation, which is used to expel said formulation using a bag or can in can system. In this way it is possible to reduce the amount of propellant within the formulation and avoid unwanted gaseous effects, for example in vaginal applications, but still provide good expulsion from the canister, where the foamable formulation is expelled sufficiently quickly but without jetting or noise. So by way of example, between about 1% to 3%;
or between about 2% to 4%; between about 3% to 5% propellant (ratio of formulation to propellant of 100: 1 to 3; 100: 2 to 4; 100: 3 to 5; respectively) is part of the formulation and a further amount of propellant is separate form the formulation and helps expel the formulation. In one or more embodiments a similar amount of propellant is in the formulation and a pump or other mechanical means is used to provide the additional expulsion force.
Modulating Agent
[0115] In one or more embodiments the modulating agent is used in a waterless composition which is surfactant and adjuvant free. The term modulating agent is used to describe an agent which can improve the stability of or stabilize a carrier or a foamable composition and/or an active agent by modulating the effect of a substance or residue present in the carrier or composition. The substance or residue may, for example, be acidic or basic or buffer system (or combinations thereof) and potentially alter an artificial pH in a waterless or substantially non-aqueous environment, such as, by acting to modulate the ionic or polar characteristics and any acidity or basesity balance of a waterless or substantially non-aqueous carrier, composition, foamable carrier or foamable composition or resultant foam or it may be a chelating or sequestering or complexing agent or it may be one or more metal ions which may act as a potential catalyst in a waterless or substantially non-aqueous environment or it may be an ionization agent or it may be an oxidizing agent.
[0116] In an embodiment, the modulating or additional component is a pH
adjusting agent or a buffering agent and can be any of the known buffering systems used in pharmaceutical or cosmetic formulations as would be appreciated by a man of the art. It can also be an organic acid, a carboxylic acid, a fatty acid an amino acid, an aromatic acid, an alpha or beta hydroxyl acid an organic base or a nitrogen containing compound.
adjusting agent or a buffering agent and can be any of the known buffering systems used in pharmaceutical or cosmetic formulations as would be appreciated by a man of the art. It can also be an organic acid, a carboxylic acid, a fatty acid an amino acid, an aromatic acid, an alpha or beta hydroxyl acid an organic base or a nitrogen containing compound.
[0117] In one or more further embodiments the modulating agent is used to describe an agent, which is a chelating or sequestering or complexing agent that is sufficiently soluble or functional in the waterless solvent to enable it to "mop up" or "lock" metal ions such as EDTA or other such pharmaceutically or cosmetically acceptable.
[0118] Modulating agents may be added to the compositions of the subject invention, preferably from about 0.1 % to about 10%, more preferably from about I% to about 5 %, of the composition. Where the active agent itself is the modulating agent alone or in combination with another modulating agent it will be added at an effective dose which may be outside these ranges.
For example azaleic acid may be at about 15% of the composition. In an embodiment sufficient modulating agent is added to achieve an artificial pH in which the active agent is preferably stable. Such artificial pH may be acidic, maybe basic or may be neutral
For example azaleic acid may be at about 15% of the composition. In an embodiment sufficient modulating agent is added to achieve an artificial pH in which the active agent is preferably stable. Such artificial pH may be acidic, maybe basic or may be neutral
[0119] Further detail regarding modulating agents is found in co-pending Published U.S.
Patent Application 2008/0206159, which is hereby incorporated in its entirety by reference.
Patent Application 2008/0206159, which is hereby incorporated in its entirety by reference.
[0120] The modulating agent to the foamable composition is useful for stabilizing pharmaceutical and cosmetic active agents which are unstable in certain pH
conditions. It is known, for example, that active agents, which contain ester bond in their structure, tend to undergo hydrolysis of the ester bond at basic pH levels. Therefore, the addition of an agent, avoids the formation of basic pH condition, and thus, prevents degradation of such active agents.
Many steroid compounds are known to undergo rearrangement at high pH, and again, adding an acidic modulating agent helps prevent such degradation. Another example of a pH-sensitive active agent is vitamin D, which degrades at low pH levels. In such a case, the addition of a basic modulating agent, such as triethanolamine is useful to maintain acceptable stability of this active agent.
conditions. It is known, for example, that active agents, which contain ester bond in their structure, tend to undergo hydrolysis of the ester bond at basic pH levels. Therefore, the addition of an agent, avoids the formation of basic pH condition, and thus, prevents degradation of such active agents.
Many steroid compounds are known to undergo rearrangement at high pH, and again, adding an acidic modulating agent helps prevent such degradation. Another example of a pH-sensitive active agent is vitamin D, which degrades at low pH levels. In such a case, the addition of a basic modulating agent, such as triethanolamine is useful to maintain acceptable stability of this active agent.
[0121] It is important to maintain skin surface pH in order to prevent susceptibility to bacterial skin infections or skin damage and disease. Thus, adding a modulating agent, which contributes to the stabilization of skin pH at the desirable level, is advantageous.
[0122] In the same fashion, adding an acidic modulating agent to a foamable composition, which is intended for vaginal application is advantageous, since better protection against vaginal infection is attained in pH lower than 4.
[0123] In one or more embodiments, the modulating agent may also be a preservative or an antioxidant or an ionization agent. Any preservative, antioxidant or ionization agents suitable for pharmaceutical or cosmetic application may be used. Non-limiting examples of antioxidants are tocopherol, tocopherol succinate, ascorbic acid (vitamin C) and its salts, propyl galate, butylated hydroxy toluene and butyl hydroxy anisol. Non-limiting examples of positive ionization agents are benzyl conium chloride, and cetyl pyridium chloride. Non-limiting examples of negative ionization agents are sodium lauryl sulphate, sodium lauryl lactylate and phospholipids. In one or more embodiments the modulating agent is a flavonoid for example quercitin and/or rutin.
[0124] A safe and effective amount of an anti-oxidant/radical scavenger may be added to the compositions of the subject invention, preferably from about 0.1 % to about 10%, more preferably from about 1% to about 5%, of the composition.
[0125] In one or more embodiments the modulating agent used is compatible with the active ingredient(s).
Ophthalmic Excipients
Ophthalmic Excipients
[0126] In one or more embodiments the formulation may comprise excipients that are suitable for ophthalmic use. By virtue of their suitability for ophthalmic use they may in certain embodiments be applicable on other sensitive targets such as for use internal and or external wounds or burns or in body cavities. Excipients selected as part of a drug carrier that can be used with the active pharmaceutical ingredients are identified by compatibility studies with active ingredients to ascertain which are compatible for use with the active pharmaceutical ingredients, for example, by examining which do not react with and or promote break down of the active pharmaceutical ingredients.
[0127] Not all excipients are appropriate for opthlmic use. Some may not be approved and require additional studies to achieve regulatory approval. Some may be eliminated as incompatible with the active ingredient and some may be eliminated agents because of physical considerations (e.g. as indicated below). Some may have or require that an effect be modified by the addition of other ingredients (e.g. such as rheology modifiers).
[0128] Oleaginous ointments are viscous preparations, which remain viscous when applied to the skin or other body surfaces; and they require extensive rubbing. Because of their viscosity, eye ointments cause blurred vision and consequent low tolerability, especially for long term treatment. Because of their high viscosity, drugs are trapped in the vehicle and cannot migrate through to their target site of action, for example, the skin or the eye.
[0129] Liquid, non viscous oleaginous medications are also disadvantageous, as they spill easily and thus, are very inconvenient to use. In eye treatment, liquid drops are difficult to apply and they require lying on the back at rest for accurate administration.
Furthermore, because of their low viscosity, liquid oil vehicles cannot carry suspended drugs, which tend to precipitate and if the viscosity is not high enough, thereby impairing the uniformity of the therapeutic product.
Furthermore, because of their low viscosity, liquid oil vehicles cannot carry suspended drugs, which tend to precipitate and if the viscosity is not high enough, thereby impairing the uniformity of the therapeutic product.
[0130] In one or more embodiments the formulations are not highly viscous. In one or more other embodiments the formulations do not provide low viscosity. In one or more embodiments the formulations are thixotropic so that on application of shear force their viscosity decreases and they become more flowable. On one or more embodiments the formulations are foams which are breakable on shear force. In one or more embodiments the foams are based on thixotropic gel formulations. In one or more embodiments the viscosity of the formulation prior to addition of propellant is more than about 1000cps and less than about 25,000 cps.
Additional components
Additional components
[0131] In an embodiment, a composition disclosed herein includes one or more additional components. Such additional components include but are not limited to anti perspirants, anti-static agents, bulking agents, cleansers, colorants, skin conditioners, deodorants, diluents, dyes, fragrances, hair conditioners, herbal extracts, humectants, keratolytic agents, modulating agents, pearlescent aids, perfuming agents, pH modifying or stabilizing agents, skin penetration or permeation enhancers, softeners, solubilizers, sunscreens, sun blocking agents, sunless tanning agents, viscosity modifiers, flavanoids and vitamins. As is known to one skilled in the art, in some instances a specific additional component may have more than one activity, function or effect.
[0132] In certain embodiments, the additional component is an oil soluble preservative, or an oil soluble antioxidant, or an oil soluble radical scavenger, or an oil soluble complexing agent, or an oil soluble pigment or dye.
Definitions
Definitions
[0133] All % values are provided on a weight (w/w) basis.
[0134] By the term "about" herein it is meant that a figure or range of figures can vary plus or minus up to 30%. So in this embodiment if a figure of "about 1" is provided then the amount can be up to 1.3 or from 0.70. In other embodiments it can reflect a variation of plus or minus 20%. In still further embodiments it can describe a variation of plus or minus 10%. In still further embodiments it can describe a variation of plus or minus 5%. As will be appreciated by one of the art there is some reasonable flexibility in formulating compositions such that where one or more ingredients are varied successful formulations may still be made even if an amount falls slightly outside the range. Therefore, to allow for this possibility amounts are qualified by about.
In one or more other embodiments the figures may be read without the prefix about.
In one or more other embodiments the figures may be read without the prefix about.
[0135] The term "waterless," as used herein, means that the composition contains no, or substantially no, free or unassociated or absorbed water. Similarly, "waterless" or "substantially waterless" carriers contain at most incidental and trace amounts of water.
[0136] By the term "single phase" herein it is meant that after addition of propellant to the composition or carrier, the liquid components of the foamable composition or carrier are fully miscible, and the solid components if any, are either dissolved or suspended in the composition.
By substantially a single phase is meant that the composition or carrier after addition of propellant is primarily or essentially a single phase as explained above, but may also have present a small amount of material which is capable of forming or may form a separate phase amounting to less than about 5% of the composition or carrier after the addition of propellant, preferably less than about 3%, and more preferably less than about 1%.
By substantially a single phase is meant that the composition or carrier after addition of propellant is primarily or essentially a single phase as explained above, but may also have present a small amount of material which is capable of forming or may form a separate phase amounting to less than about 5% of the composition or carrier after the addition of propellant, preferably less than about 3%, and more preferably less than about 1%.
[0137] The term "unstable active agent" as used herein, means an active agent which is oxidized and/or degraded within less than a day, and in some cases, in less than an hour upon exposure to air, light, skin or water under ambient conditions.
[0138] The term "co-surfactant" as used herein, means a molecule which on its own is not able to form and stabilize satisfactorily an oil in water emulsion but when used in combination with a surfactant the co-surfactant has properties, which can allow it to help surfactants to create an emulsion and can boost the stabilizing power or effect of the surfactant and can include, for example, a fatty alcohol, such as cetyl alcohol or a fatty acid such as stearic acid. Cetyl alcohol is a waxy hydrophobic substance that can be emulsified with water using a surfactant. Some substances may have more than one function and for example, fatty alcohols can in some formulations act as a co-solvent. In certain circumstances a co-surfactant can itself be converted in to a surfactant or soap by, for example, adding a base, such as, triethanolamine to a fatty acid like stearic acid.
[0139] The identification of a "polyol", as used herein, is an organic substance that contains at least two hydroxy groups in its molecular structure.
[0140] In one or more embodiments, the polyol is a diol (a compound that contains two hydroxy groups in its molecular structure). Examples of diols include propylene glycol (e.g., 1,2-propylene glycol and 1,3-propylene glycol), butanediol (e.g., 1,2-butanediol, 1,3-butanediol, 2,3-butanediol and 1,4-butanediol), butanediol (e.g., 1,3-butanediol and 1,4-butenediol), butynediol, pentanediol (e.g., pentane-1,2-diol, pentane-1,3-diol, pentane-1,4-diol, pentane-1,5-diol, pentane-2,3 -diol and pentane-2,4-diol), hexanediol (e.g., hexane- 1,6-diol hexane-2,3 -diol and hexane-2,56-diol), octanediol (e.g., 1,8-octanediol), neopentyl glycol, 2-methyl-1,3-propanediol, diethylene glycol, triethylene glycol, tetraethylene glycol, dipropylene glycol and dibutylene glycol.
[0141] In one or more embodiments, the polyol is a triol (a compound that contains three hydroxy groups in its molecular structure), such as glycerin, butane-1,2,3-triol, butane-1,2,4-triol and hexane-1,2,6-triol.
[0142] In one or more embodiments, the polyol is a saccharide. Exemplary saccharides include, but are not limited to monosaccharide, disaccharides, oligosaccharides and sugar alcohols.
[0143] A monosaccharide is a simple sugar that cannot be hydrolysed to smaller units.
Empirical formula is (CH2O)n and range in size from trioses (n=3) to heptoses (n=7).
Exemplary monosaccharide compounds are ribose, glucose, fructose and galactose.
Empirical formula is (CH2O)n and range in size from trioses (n=3) to heptoses (n=7).
Exemplary monosaccharide compounds are ribose, glucose, fructose and galactose.
[0144] Disaccharides are made up of two monosaccharides joined together, such as sucrose, maltose and lactose.
[0145] In one or more embodiments, the polyol is a sugar alcohol (also known as a polyol, polyhydric alcohol, or polyalcohol) is a hydrogenated form of saccharide, whose carbonyl group (aldehyde or ketone, reducing sugar) has been reduced to a primary or secondary hydroxyl group.
They are commonly used for replacing sucrose in foodstuffs, often in combination with high intensity artificial sweeteners to counter the low sweetness. Some exemplary sugar alcohols, which are suitable for use according to the present invention are mannitol, sorbitol, xylitol, maltitol, lactitol. (Maltitol and lactitol are not completely hydrogenated compounds - they are a monosaccharide combined with a polyhydric alcohol.) Mixtures of polyols, including (1) at least one polyol selected from a diol and a triol; and (2) a saccharide are contemplated within the scope of the present disclosure.
They are commonly used for replacing sucrose in foodstuffs, often in combination with high intensity artificial sweeteners to counter the low sweetness. Some exemplary sugar alcohols, which are suitable for use according to the present invention are mannitol, sorbitol, xylitol, maltitol, lactitol. (Maltitol and lactitol are not completely hydrogenated compounds - they are a monosaccharide combined with a polyhydric alcohol.) Mixtures of polyols, including (1) at least one polyol selected from a diol and a triol; and (2) a saccharide are contemplated within the scope of the present disclosure.
[0146] According to some embodiments, the composition is polyol-free i.e., free of polyols.
In other embodiments, the composition is substantially free and comprises less than about 5%
final concentration of polyols, preferably less than 2%, more preferably less than 1%. Where a formulation includes insignificant amounts of polyols it is considered to be essentially free of them.
In other embodiments, the composition is substantially free and comprises less than about 5%
final concentration of polyols, preferably less than 2%, more preferably less than 1%. Where a formulation includes insignificant amounts of polyols it is considered to be essentially free of them.
[0147] In an embodiment, the polyol is linked to a hydrophobic moiety. In the context of the present disclosure, a polyol linked to a hydrophobic moiety is still defined as a "polyol" as long as it still contains two or more free hydroxyl groups.
[0148] In an embodiment, the polyol is linked to a hydrophilic moiety. In the context of the present disclosure, a polyol linked to a hydrophilic moiety is still defined "polyol" as long as it still contains two or more free hydroxyl groups.
[0149] The term "water activity" as used herein, activity represents the hydroscopic nature of a substance; or the tendency of a substance that absorbs water from its surroundings.
Microorganisms require water to grow and reproduce, and such water requirements are best defined in terms of water activity of the substrate. The water activity of a solution is expressed as Aw = P/Po, where P is the water vapor pressure of the solution and Po is the vapor pressure of pure water at the same temperature. Every microorganism has a limiting Aw, below which it will not grow; e.g., for Streptococci, Klebsiella spp, Escherichia coli, Clostridium perfringens, and Pseudomonas spp, the Aw value is 0.95. Staphylococcus aureus is most resistant and can proliferate with an Aw as low as 0.86, and fungi can survive at Aw of at least 0.7. In one or more embodiments, the concentration of the hydrophobic solvent, and/or foaming agent in the composition is selected to provide an Aw value selected from the ranges of (1) about 0.8 and about 0.9; (2) about 0.7 and about 0.8; and (3) less than about 0.7.
Delivering the formulation in a pressurized package does not allow for humidity to be absorbed by the preparation, and therefore, the water free character of the composition cannot be damaged.
Microorganisms require water to grow and reproduce, and such water requirements are best defined in terms of water activity of the substrate. The water activity of a solution is expressed as Aw = P/Po, where P is the water vapor pressure of the solution and Po is the vapor pressure of pure water at the same temperature. Every microorganism has a limiting Aw, below which it will not grow; e.g., for Streptococci, Klebsiella spp, Escherichia coli, Clostridium perfringens, and Pseudomonas spp, the Aw value is 0.95. Staphylococcus aureus is most resistant and can proliferate with an Aw as low as 0.86, and fungi can survive at Aw of at least 0.7. In one or more embodiments, the concentration of the hydrophobic solvent, and/or foaming agent in the composition is selected to provide an Aw value selected from the ranges of (1) about 0.8 and about 0.9; (2) about 0.7 and about 0.8; and (3) less than about 0.7.
Delivering the formulation in a pressurized package does not allow for humidity to be absorbed by the preparation, and therefore, the water free character of the composition cannot be damaged.
[0150] In an embodiment no preservative is added because the formulation is a waterless hydrophobic solvent or oil-based formulation having an Aw (Water Activity) value of less than 0.9, less, or less than about 0.8, or less than about 0.7 or less than about 0.6 and preferably less than about 0.5 which is below the level of microbial proliferation.
[0151] In one or more embodiments, the hydrophobic carrier composition further contains an anti-infective agent, selected from the group of an antibiotic agent, an antibacterial agent, an antifungal agent, an agent that controls yeast, an antiviral agent and an antiparasitic agent. In a preferred embodiment the anti infective agent comprises a tricyclic antibiotic. Not only can combining the anti-infective effect of a hydrophobic carrier composition, with an anti-infective agent can result in a synergistic effect and consequently higher success rate of the treatment but the combination with the foaming agent achieves a formulation which is physically stable as demonstrated herein in the Examples. Moreover the use of hydrophobic based water free formulation can maximize the antimicrobial potential of the formulations.
Storage in sealed, light and airtight canisters can assist in preserving the formulations.
Storage in sealed, light and airtight canisters can assist in preserving the formulations.
[0152] The identification of a "solvent," as used herein, is not intended to characterize the solubilization capabilities of the solvent for any specific active agent or any other component of the foamable composition. Rather, such information is provided to aid in the identification of materials suitable for use as a part in the foamable carriers described herein.
Substantially Alcohol Free
Substantially Alcohol Free
[0153] Lower or short chain alcohols, having up to 5 carbon atoms in their carbon chain skeleton, such as ethanol, propanol, isopropanol, butanol, iso-butanol, t-butanol and pentanol are considered less desirable solvents or co-solvents due to their skin-irritating effect. Thus, according to some embodiments, the composition is substantially alcohol-free i.e., free of short chain alcohols. In other embodiments, the composition comprises less than about 5% final concentration of lower alcohols, preferably less than 2%, more preferably less than 1%. Where a formulation contains insignificant amounts of short chain alcohols it is considered to be essentially free of them.
Substantially Surfactant Free
Substantially Surfactant Free
[0154] Surfactants have been categorized in to various sub classes depending on their ionic characteristics, namely non-ionic surfactants, anionic, cationic, zwitterionic, amphoteric and amphiphilic surfactants. The term surfactant has been often loosely used in the art to include substances which do not function effectively as stand alone surfactants to reduce surface tension between two substances or phases. Reduction of surface tension can be significant in foam technology in relation to the ability to create small stable bubbles. For example fatty alcohols, fatty acids and certain waxes are amphiphatic, are essentially hydrophobic with a minor hydrophilic region and for the purposes of forming an emulsion they are usually regarded as an oil and thus have a "required" HLB value" for the purpose of determining what standard surfactant might be appropriate to use with the oil phase. However unlike standard or customary surfactants, these substances are not effective as stand-alone surfactants in foamable emulsion compositions, because of their very weak emulsifying capacity and further due to their weak foaming capacity on their own. They are occasionally used in a supporting role as co-emulsifiers, i.e., in combination with a standard surfactant but are commonly used as thickeners and have successfully been used as foam adjuvants to assist customary surfactants to boost foam quality and stability. For clarification, in the context herein, the term "standard surfactant" or "customary surfactant" refers herein to customary non-ionic, anionic, cationic, zwitterionic, amphoteric and amphiphilic surfactants. A fatty alcohol or a fatty acid and certain waxes are not regarded as a standard surfactant. However, in contrast, an ether or an ester formed from such fatty alcohols or fatty acids can be regarded as a customary surfactant.
[0155] Generally, surfactants are known to possess irritation potential. One way that is used to try and reduce potential irritation and drying of the skin or mucosa due to surfactants and their repeated use especially when formulations are to be left on the skin or mucosa rather than being washed off is to use essentially or primarily non ionic surfactants at preferably low concentrations below 5%. The current breakthrough of identifying formulations which produce quality breakable foam yet omitting customary surfactants from a composition may contribute to improved tolerability of such a composition and can be an important advantage.
This is especially so when a formulation is to be applied to a very sensitive target site, and particularly so on a repeated basis.
This is especially so when a formulation is to be applied to a very sensitive target site, and particularly so on a repeated basis.
[0156] Non-limiting examples of classes of customary non-ionic surfactants include: (i) polyoxyethylene sorbitan esters (polysorbates), such as polysorbate 20, polysorbate 40, polysorbate 60 and polysorbate 80; (ii) sorbitan esters, such as sorbitan monostearate sorbitan monolaurate and sorbitan monooleate; (iii) polyoxyethylene fatty acid esters, such as PEG-8 stearate, PEG-20 stearate, PEG-40 stearate, PEG-100 stearate, PEG-8 laurate, PEG-10 laurate, PEG-12 laurate, PEG-20 laurate, PEG-8 oleate, PEG-9 oleate, PEG-10 oleate, PEG-12 oleate, PEG-15 oleate and PEG-20 oleate; (iv) PEG-fatty acid diesters, such as PEG-150 distearate, (v) polyethylene glycol (PEG) ethers of fatty alcohols, such as ; (vi) glycerol esters, such as glycerol monostearate, glycerol monolaurate, glycerol monopalmitate and glycerol monooleate; (vii) PEG-fatty acid mono- and di-ester mixtures; (viii) polyethylene glycol glycerol fatty acid esters;
(ix) propylene glycol fatty acid esters; (x) mono- and diglycerides; (xi) sugar esters (mono-, di-and tri-esters of sucrose with fatty acids) and (xii) polyethylene glycol alkyl phenols.
(ix) propylene glycol fatty acid esters; (x) mono- and diglycerides; (xi) sugar esters (mono-, di-and tri-esters of sucrose with fatty acids) and (xii) polyethylene glycol alkyl phenols.
[0157] In certain embodiments, the composition is free of customary surfactants, or "surfactant-free" and in certain embodiments the foamable composition is substantially free of customary surfactants, or "substantially surfactant-free".
[0158] In the context herein, the term "substantially surfactant-free composition" relates to a composition that contains a total of less than about 0.4% of a surfactant selected from the group consisting of customary non-ionic, anionic, cationic, zwitterionic, amphoteric and ampholytic surfactants. Preferably, the composition comprises less than about 0.3% or less than about 0.2%
by weight of a standard surfactant and more preferably less than about 0.1 %.
Where a formulation includes insignificant amounts of surfactants it is considered to be essentially free of them.
by weight of a standard surfactant and more preferably less than about 0.1 %.
Where a formulation includes insignificant amounts of surfactants it is considered to be essentially free of them.
[0159] Non-surfactant or surfactant-free compositions will comprise no or negligible levels of surface active agents.
[0160] In additional embodiments, the term "substantially surfactant-free"
relates to a composition wherein the ratio between the foaming agent and the surfactant is between 50:1 or 20:1; or between 20:1 and 10:1 or between 100:1 and 20:1.
relates to a composition wherein the ratio between the foaming agent and the surfactant is between 50:1 or 20:1; or between 20:1 and 10:1 or between 100:1 and 20:1.
[0161] In certain embodiments, the composition is free or substantially free of an ionic surfactant. In certain embodiments, the composition is free or substantially free of a non-ionic surfactant.
Substantially Polymer-Free
Substantially Polymer-Free
[0162] By the term polymeric agent it is intended to mean a compound having multiple repeated units such as cellulose polymers, acrylic polymers, block polymers and copolymers. In one or more certain embodiments the polymeric agent has a molecular weight of in excess of a 1000 Daltons. In one or more embodiments the formulations are substantially polymer free. In one or more embodiments the formulations are substantially polymer free of a polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent, being locust bean gum, sodium alginate, sodium caseinate, egg albumin, gelatin agar, carrageenin gum, sodium alginate, xanthan gum, quince seed extract, tragacanth gum, guar gum, cationic guars, hydroxypropyl guar gum, starch, amine-bearing polymers such as chitosan; acidic polymers obtainable from natural sources, such as alginic acid and hyaluronic acid; chemically modified starches and the like, carboxyvinyl polymers, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidene chloride polymers, semi-synthetic polymeric materials such as cellulose ethers, such as methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxy propylmethyl cellulose, methylhydroxyethylcellulose, methylhydroxypropylcellulose, hydroxyethylcarboxymethylcellulose, carboxymethyl cellulose, carboxymethylcellulose carboxymethylhydroxyethylcellulose, and cationic celluloses, carbomer (homopolymer of acrylic acid is crosslinked with an allyl ether pentaerythritol, an allyl ether of sucrose, or an allyl ether of propylene); poloxamers (synthetic block copolymer of ethylene oxide and propylene) ;
polyethylene glycol having molecular weight of 1000 or more (e.g., PEG 1,000, PEG 4,000, PEG
6,000 and PEG 10,000) and which could function as a hydro alcoholic foam booster.. By substantially polymer free it is intended to mean less than about 5%, preferably less than about 2%. By essentially polymer free it is intended to mean less than about I%, preferably less than about 0.5%. In further embodiments they are essentially polymer free and in still further embodiments they are free of polymeric agents.
polyethylene glycol having molecular weight of 1000 or more (e.g., PEG 1,000, PEG 4,000, PEG
6,000 and PEG 10,000) and which could function as a hydro alcoholic foam booster.. By substantially polymer free it is intended to mean less than about 5%, preferably less than about 2%. By essentially polymer free it is intended to mean less than about I%, preferably less than about 0.5%. In further embodiments they are essentially polymer free and in still further embodiments they are free of polymeric agents.
[0163] In alternative embodiments the formulations may comprise a polymeric agent in such case the polymeric agents are oil soluble polymeric agents. Non limiting examples of oil-soluble polymeric agents are: Ethyl cellulose, alkylated guar gum, trimethylsiloxysilicate, alkyl-modified silicone, polyamide-modified silicone, homopolymers and copolymers of alkyl methacrylates, alkyl acrylates, and alkyl styrenes polyisobutene, polybutyl metacrylate, polycyclohexylstyrene.
[0164] According to one or more embodiments, the composition comprises less than about 0.1 % by weight of a polymeric agent and more preferably less than about 0.05 %. t Polymer-free compositions will comprise no or negligible levels of polymeric agents.
[0165] In the art, the term polymeric agent can be used loosely to refer to any polymer.
However, in some embodiments polymers that do not have a gel building role but may act in other ways are not excluded from the compositions. In one or more embodiments a polyether siloxane copolymer and a poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer and the like, which can provide a good feeling to the composition are not excluded.
Physical characteristics of the foamable composition and foam
However, in some embodiments polymers that do not have a gel building role but may act in other ways are not excluded from the compositions. In one or more embodiments a polyether siloxane copolymer and a poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer and the like, which can provide a good feeling to the composition are not excluded.
Physical characteristics of the foamable composition and foam
[0166] A foamable composition manufactured according to one or more embodiments herein is very easy to use. When applied onto the afflicted body surface of mammals, i.e., humans or animals, it is in a foam state, allowing free application without spillage.
Upon further application of a mechanical force, e.g., by rubbing the composition onto the body surface, it freely spreads on the surface and is rapidly absorbed.
Upon further application of a mechanical force, e.g., by rubbing the composition onto the body surface, it freely spreads on the surface and is rapidly absorbed.
[0167] In one or more embodiments the foamable composition is a single phase solution. In one or more embodiments the foamable composition is substantially a single phase solution. In certain circumstances, where the active agent is insoluble and is presented as a homogenous suspension, the formulation is turbid or cloudy.
[0168] In one or more embodiments the foam composition has an acceptable shelf-life of at least six months or at least nine months or at least one year, or of at least about one and a half years or at least two years at ambient temperature. A feature of a product for cosmetic or medical use is long term stability. Propellants, which are a mixture of low molecular weight hydrocarbons, tend to impair the stability. The foamable compositions herein are surprisingly stable, even in the absence of customary surfactants and or foam adjuvants.
Following accelerated stability studies, they demonstrate desirable texture; they form fine bubble structures that do not break immediately upon contact with a surface, spread easily on the treated area and absorb quickly.
Following accelerated stability studies, they demonstrate desirable texture; they form fine bubble structures that do not break immediately upon contact with a surface, spread easily on the treated area and absorb quickly.
[0169] The composition should also be free flowing, to allow it to flow through the aperture of the container, e.g., and aerosol container, and create an acceptable foam.
Compositions containing a substantial amount of semi-solid hydrophobic solvents, e.g., white petrolatum, as the main ingredients of the oil phase of the emulsion, will likely exhibit high viscosity and poor flowability and can be inappropriate candidates for a foamable composition.
Thus in one or more embodiments semi-solid hydrophobic solvents are a subsidiary component in the composition, for example being present at less than about 25%, less than about 20%, less than about 15% , less than about 10%, or less than about 5% by weight of the foamable composition.
In other embodiments they can be present in higher amounts due to the solvent effect of the propellant diluting the formulation and enabling flowability or where the formulation is presented as a gel or ointment.
Foam Quality
Compositions containing a substantial amount of semi-solid hydrophobic solvents, e.g., white petrolatum, as the main ingredients of the oil phase of the emulsion, will likely exhibit high viscosity and poor flowability and can be inappropriate candidates for a foamable composition.
Thus in one or more embodiments semi-solid hydrophobic solvents are a subsidiary component in the composition, for example being present at less than about 25%, less than about 20%, less than about 15% , less than about 10%, or less than about 5% by weight of the foamable composition.
In other embodiments they can be present in higher amounts due to the solvent effect of the propellant diluting the formulation and enabling flowability or where the formulation is presented as a gel or ointment.
Foam Quality
[0170] Foam quality can be graded as follows:
Grade E (excellent): very rich and creamy in appearance, does not show any bubble structure or shows a very fine (small) bubble structure; does not rapidly become dull; upon spreading on the skin, the foam retains the creaminess property and does not appear watery.
Grade G (good): rich and creamy in appearance, very small bubble size, "dulls"
more rapidly than an excellent foam, retains creaminess upon spreading on the skin, and does not become watery.
Grade FG (fairly good): a moderate amount of creaminess noticeable, bubble structure is noticeable; upon spreading on the skin the product dulls rapidly and becomes somewhat lower in apparent viscosity.
Grade F (fair): very little creaminess noticeable, larger bubble structure than a "fairly good" foam, upon spreading on the skin it becomes thin in appearance and watery.
Grade P (poor): no creaminess noticeable, large bubble structure, and when spread on the skin it becomes very thin and watery in appearance.
Grade VP (very poor): dry foam, large very dull bubbles, difficult to spread on the skin.
Grade E (excellent): very rich and creamy in appearance, does not show any bubble structure or shows a very fine (small) bubble structure; does not rapidly become dull; upon spreading on the skin, the foam retains the creaminess property and does not appear watery.
Grade G (good): rich and creamy in appearance, very small bubble size, "dulls"
more rapidly than an excellent foam, retains creaminess upon spreading on the skin, and does not become watery.
Grade FG (fairly good): a moderate amount of creaminess noticeable, bubble structure is noticeable; upon spreading on the skin the product dulls rapidly and becomes somewhat lower in apparent viscosity.
Grade F (fair): very little creaminess noticeable, larger bubble structure than a "fairly good" foam, upon spreading on the skin it becomes thin in appearance and watery.
Grade P (poor): no creaminess noticeable, large bubble structure, and when spread on the skin it becomes very thin and watery in appearance.
Grade VP (very poor): dry foam, large very dull bubbles, difficult to spread on the skin.
[0171] Topically administrable foams are typically of quality grade E or G, when released from the aerosol container. Smaller bubbles are indicative of a more stable foam, which does not collapse spontaneously immediately upon discharge from the container. The finer foam structure looks and feels smoother, thus increasing its usability and appeal.
Foam Density
Foam Density
[0172] Another property of the foam is specific gravity or density, as measured upon release from the aerosol can. Typically, foams have specific gravity of less than 0.50 g/mL or less than 0.12 g/mL, depending on their composition and on the propellant concentration.
In one or more embodiments the foam density is about less than 0.3g/mL or is about less than 0.2g/mL; or is about less than 0.1g/mL or is about less than 0.05g/mL.
Shakability
In one or more embodiments the foam density is about less than 0.3g/mL or is about less than 0.2g/mL; or is about less than 0.1g/mL or is about less than 0.05g/mL.
Shakability
[0173] `Shakability' means that the composition contains some or sufficient flow to allow the composition to be mixed or remixed on shaking. That is, it has fluid or semi fluid properties.
Shakability is described further in examples in Tests section. In one or more certain limited embodiments the formulation is poorly shakable but is nevertheless flowable.
Breakability / collapse time
Shakability is described further in examples in Tests section. In one or more certain limited embodiments the formulation is poorly shakable but is nevertheless flowable.
Breakability / collapse time
[0174] A further aspect of the foam is breakability. The balance between stability and breakability of the foam coming out of the container is very delicate: on the one hand the foam should preferably not be "quick breaking", i.e., it should be stable upon release from the pressurized container and not break as a result of exposure to skin temperature; and on the other hand, it should be "breakable", i.e., it should spread easily, break down and absorb into the skin or membrane upon application of mild shear force. The breakable foam is thermally stable, yet breaks under shear force. Shear-force breakability of the foam is clearly advantageous over thermally-induced breakability. Thermally sensitive foams start to collapse immediately upon exposure to skin temperature and, therefore, cannot be applied on the hand and afterwards delivered to the afflicted area.
[0175] The collapse time of foam represents its tendency to be temperature-sensitive and its ability to be at least stable in the short term so as to allow a user sufficient time to comfortably handle and apply the foam to a target area without being rushed and or concerned that it may rapidly collapse, liquefy and or disappear. Collapse time, as an indicator of thermal sensitivity, is examined by dispensing a given quantity of foam and photographing sequentially its appearance with time during incubation at 36 C (the procedure is explained in further detail in the Examples). The collapse time result is defined as the time when the foam reaches 50% of its initial height. Foams which are structurally stable on the skin and have not reached 50% of their initial height after at least one minute are termed "short term stable"
carriers or foams. Simple collapse time can be measured by applying a foam sample on a body surface like the fingers at normal body temperature of about 37 C.
carriers or foams. Simple collapse time can be measured by applying a foam sample on a body surface like the fingers at normal body temperature of about 37 C.
[0176] Oils may cause foam to be thermolabile and "quick breaking." However, in certain embodiments herein, despite the presence of high oil content, quite unexpectedly the foam is substantially thermally stable. By "substantially thermally stable" it is meant that the foam upon application onto a warm skin or body surface at about 35-37 C it does not collapse within about 30 seconds. Thus, in one or more embodiments the simple collapse time of the foam is more than about 30 seconds or more than about one minute or more than about two minutes.
In one or more limited embodiments simple collapse time can be a little shorter than 30 seconds, but not less than about 20 seconds. In one or further or alternative embodiments the collapse time is measured by introducing a sample of foam into an incubator at 36 C and the collapse time of the foam is more than 30 seconds or more than about one minute or more than about two minutes.
PHARMACEUTICAL COMPOSITION
In one or more limited embodiments simple collapse time can be a little shorter than 30 seconds, but not less than about 20 seconds. In one or further or alternative embodiments the collapse time is measured by introducing a sample of foam into an incubator at 36 C and the collapse time of the foam is more than 30 seconds or more than about one minute or more than about two minutes.
PHARMACEUTICAL COMPOSITION
[0177] The foamable oleaginous composition of the present invention can be used by itself as a topical treatment of a body surface, as many hydrophobic solvents such as emollients, unsaturated oils, essential oils or therapeutic oils that possess cosmetic or medical beneficial effects. Furthermore, it is an ideal vehicle for active pharmaceutical ingredients and active cosmetic ingredients. In the context active pharmaceutical ingredients and active cosmetic ingredients are collectively termed "active agent" or "active agents". The absence of surfactants in the composition is especially advantageous, since no surfactant-related adverse reactions are expected from such a composition. Some surfactants may act to facilitate gelling of the pre-foam formulation. The absence of such surfactants may avoid this undesirable phenomenon. In one or more embodiments the active agent is soluble in the composition of a phase thereof. In one or more other embodiments it is partially soluble or insoluble. When partially soluble or insoluble the active agent is presented as a suspension or it can be encapsulated in a carrier.
[0178] Whilst some active ingredients are effectively inert in the wax/solvent compositions described herein other active ingredients are very sensitive to degradation and can react, break down or rearrange readily. For example, tetracycline antibiotics such as minocycline or doxycycline break down upon being exposed to many excipients as disclosed in the study described in Example 9. Thus, in one or more embodiments an active agent is first tested for compatibility with each of the formulation ingredients. In one or more embodiments the active agent is compatible with the other ingredients.
[0179] Suitable active agents include but are not limited to an active herbal extract, an acaricides, an age spot and keratose removing agent, an allergen, an alpha hydroxyl acid, an analgesic agent, an androgen, an antiacne agent, an antiallergic agent, an antiaging agent, an antibacterial agent, an antibiotic, an antiburn agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic anent, an antifungal agent, an antihistamine, an antihelminth agent, an anti-hyperkeratosis agent, an anti-infective agent, an antiinflammatory agent, an antiirritant, an antilipemic agent, an antimicrobial agent, an antimycotic agent, an antioxidant, an antiparasitic agent, an antiproliferative agent, an antipruritic agent, an antipsoriatic agent, an antirosacea agent, an antiseborrheic agent, an antiseptic agent, an antiswelling agent, an antiviral agent, an anti-wart agent, an anti-wrinkle agent, an anti-yeast agent, an astringent, a beta-hydroxy acid, benzoyl peroxide, a cardiovascular agent, a chemotherapeutic agent, a corticosteroid, an immunogenic substance, a dicarboxylic acid, a disinfectant, an estrogen, a fungicide, a hair growth regulator, a haptene, a hormone, a hydroxy acid, an immunosuppressant, an immunoregulating agent, an immunomodulator, an immunostimulant, an insecticide, an insect repellent, a keratolytic agent, a lactam, a local anesthetic agent, a lubricating agent, a masking agent, a metal, a metal oxide, a mitocide, a neuropeptide, a non-steroidal anti-inflammatory agent, an oxidizing agent, a pediculicide, a peptide, a pesticide, a progesterone, a protein, a photodynamic therapy agent, a radical scavenger, a refatting agent, a retinoid, a sedative agent, a scabicide, a self tanning agent, a skin protective agent, a skin whitening agent, a steroid, a steroid hormone, a vasoactive agent, a vasoconstrictor, a vasodilator, a vitamin, a vitamin A, a vitamin A derivative, a vitamin B, a vitamin B
derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D
derivative, a vitamin D
analog, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K
derivative, a wound healing agent and a wart remover. As is known to one skilled in the art, in some instances a specific active agent may have more than one activity, function or effect.
Encapsulation of an active agent
derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D
derivative, a vitamin D
analog, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K
derivative, a wound healing agent and a wart remover. As is known to one skilled in the art, in some instances a specific active agent may have more than one activity, function or effect.
Encapsulation of an active agent
[0180] In one or more embodiments, the active agent is encapsulated in particles, microparticles, nanoparticles, microcapsules, microspheres, nanocapsules, nanospheres, liposomes, niosomes, polymer matrix, silica-gel, graphite, nanocrystals or microsponges. Such particles can have various functions, such as (1) protection of the drug from degradation; (2) modification of the drug release rate from the composition; (3) control of skin penetration profile;
and (4) mitigation of adverse effects, due to the controlled release of the active agent from the encapsulation particles.
Solubility of an active agent
and (4) mitigation of adverse effects, due to the controlled release of the active agent from the encapsulation particles.
Solubility of an active agent
[0181] Solubility of the steroid is an important factor in the development of a stable foamable composition according to the present invention.
[0182] For definition purposes, in the context of the present invention, the descriptive terminology for solubility according to the US Pharmacopoeia (USP 23, 1995, p.
10), the European Pharmacopoeia (EP, 5th Edition (2004), page 7) and several other textbooks used in the art of pharmaceutical sciences (see for example, Martindale, The Extra Pharmacopoeia, 30th Edition (1993), page xiv of the Preface; and Remington's Pharmaceutical Sciences, 18th Edition (1990), page 208) is adapted:
Descriptive Term Parts of Solvent Required for 1 Part of Solute Very soluble Less than 1 Freely soluble From 1 to 10 Soluble From 10 to 30 Sparingly soluble From 30 to 100 Slightly soluble From 100 to 1,000 Very slightly soluble From 1,000 to 10,000 Practically insoluble or Insoluble 10,000 and over
10), the European Pharmacopoeia (EP, 5th Edition (2004), page 7) and several other textbooks used in the art of pharmaceutical sciences (see for example, Martindale, The Extra Pharmacopoeia, 30th Edition (1993), page xiv of the Preface; and Remington's Pharmaceutical Sciences, 18th Edition (1990), page 208) is adapted:
Descriptive Term Parts of Solvent Required for 1 Part of Solute Very soluble Less than 1 Freely soluble From 1 to 10 Soluble From 10 to 30 Sparingly soluble From 30 to 100 Slightly soluble From 100 to 1,000 Very slightly soluble From 1,000 to 10,000 Practically insoluble or Insoluble 10,000 and over
[0183] Thus, in one or more embodiments, the active agent is "soluble", "freely soluble" or "very soluble" (as defined above) in the composition. Yet, in certain cases, the active agent is "very slightly soluble", "slightly soluble" or "sparingly soluble" in the composition.
[0184] Yet, in one or more embodiments, the active agent is insoluble i.e., "requires 10,000 parts or more of a solvent to be solubilized", in the composition.
[0185] In certain embodiments it is desirable that the active agent is maximally soluble in the composition, because solubility of the active agents is expected to increase its bioavailability.
[0186] Yet, in additional embodiments it is desirable that the active agent is insoluble in the composition, because its degradation is enhanced when it is dissolved. In such cases, the hydrophobic solvent is selected by (1) testing the solubility of said active agent in various hydrophobic solvents, followed by (2) inclusion in the composition of such solvents that do not solubilize the active agent. In one or more embodiments the active agent is presented as a suspension. In one or more further embodiments the active agent is micronized, which can assist in delivery into the skin, mucosal membrane and body cavity surfaces and also aid homogenous distribution within the formulation.
Exemplary groups of active agents Antibiotics
Exemplary groups of active agents Antibiotics
[0187] In the context of the present disclosure, an antibiotic agent is a substance, that has the capacity to inhibit the growth of or to destroy bacteria and other microorganisms.
[0188] In one or more embodiments, the antibiotic agent is selected from the classes consisting beta-lactam antibiotics, aminoglycosides, ansa-type antibiotics, anthraquinones, antibiotic azoles, antibiotic glycopeptides, macrolides, antibiotic nucleosides, antibiotic peptides, antibiotic polyenes, antibiotic polyethers, quinolones, antibiotic steroides, sulfonamides, tetracycline, dicarboxylic acids, antibiotic metals including antibiotic metal ions, oxidizing agents, a periodate, a hypochlorite, a permanganate, substances that release free radicals and/or active oxygen, cationic antimicrobial agents, quaternary ammonium compounds, biguanides, triguanides, bisbiguanides and analogs and polymers thereof, naturally occurring antibiotic compounds, including antibiotic plant oils and antibiotic plant extracts and any one of the following antibiotic compounds including non classified antibiotic compound analogs, derivatives, salts, ions, complexes and mixtures thereof.
Tetracyclines
Tetracyclines
[0189] According to some embodiments, the antibiotic agent is a tetracycline.
The tetracyclines (also referred to herein as "tetracycline antibiotics") are a group of antibacterials, originally derived from certain Streptomyces spp., having the same tetracyclic nucleus, naphthacene, and similar properties. They are usually bacteriostatic but act by interfering with protein synthesis in susceptible organisms. Tetracycline antibiotics are susceptible to degradation by oxidation.
The tetracyclines (also referred to herein as "tetracycline antibiotics") are a group of antibacterials, originally derived from certain Streptomyces spp., having the same tetracyclic nucleus, naphthacene, and similar properties. They are usually bacteriostatic but act by interfering with protein synthesis in susceptible organisms. Tetracycline antibiotics are susceptible to degradation by oxidation.
[0190] Tetracyclines include, but are not limited to, dihydrosteffimycin, demethyltetracycline, aclacinomycin, akrobomycin, baumycin, bromotetracycline, cetocyclin, chlortetracycline, clomocycline, daunorubicin, demeclocycline, doxorubicin, doxorubicin hydrochloride, doxycycline, lymecyclin, marcellomycin, meclocycline, meclocycline sulfosalicylate, methacycline, minocycline, minocycline hydrochloride, musettamycin, oxytetracycline, rhodirubin, rolitetracycline, rubomycin, serirubicin, steffimycin, tetracycline and analogs, salts and derivatives thereof.
[0191] Chlortetracycline, oxytetracycline, tetracycline, demeclocycline are all natural products that have been isolated from Streptomyces spp. The more recent tetracyclines, namely methacycline, doxycycline, and minocycline, are semisynthetic derivatives.
Methacycline, like demeclocycline, has a longer half-life than tetracycline. Minocycline is active against some tetracycline-resistant bacteria, including strains of staphylococci. Both doxycycline and minocycline are more lipid-soluble than the other tetracyclines and they penetrate well into tissues. They are thus more suitable for incorporating into oily or emollient containing formulations. However, they have a place in the treatment of chlamydial infections, rickettsial infections such as typhus and the spotted fevers, mycoplasmal infections such as atypical pneumonia, pelvic inflammatory disease, Lyme disease, brucellosis, tularaemia, plague, cholera, periodontal disease, and acne. The tetracyclines have also been useful in the treatment of penicillin-allergic patients suffering from venereal diseases, actinomycosis, bronchitis, and leptospirosis. Minocycline may sometimes be used in multidrug regimens for leprosy.
Doxycycline may be used for the treatment and prophylaxis of malaria; it is also used in the management of anthrax.
Methacycline, like demeclocycline, has a longer half-life than tetracycline. Minocycline is active against some tetracycline-resistant bacteria, including strains of staphylococci. Both doxycycline and minocycline are more lipid-soluble than the other tetracyclines and they penetrate well into tissues. They are thus more suitable for incorporating into oily or emollient containing formulations. However, they have a place in the treatment of chlamydial infections, rickettsial infections such as typhus and the spotted fevers, mycoplasmal infections such as atypical pneumonia, pelvic inflammatory disease, Lyme disease, brucellosis, tularaemia, plague, cholera, periodontal disease, and acne. The tetracyclines have also been useful in the treatment of penicillin-allergic patients suffering from venereal diseases, actinomycosis, bronchitis, and leptospirosis. Minocycline may sometimes be used in multidrug regimens for leprosy.
Doxycycline may be used for the treatment and prophylaxis of malaria; it is also used in the management of anthrax.
[0192] In an embodiment the active ingredient may be any one of the following non limiting examples chlortetracycline, demeclocycline, doxycycline, lymecycline, meclocycline, methacycline, minocycline, oxytetracycline, rolitetracycline, tetracycline. In a preferred embodiment they are doxycycline or minocycline.
[0193] Tetracycline antibiotics can be incorporated into the formulations of the present invention to treat, ameliorate or prevent a multitude of disorders responsive to tetracycline antibiotics. The formulations can be applied topically to the skin or to the genitals or to mucosal membranes and on and around the eye, sub-gingival and can be applied into a wide range of body cavities, including aural, digestive, oral, nasal, urethra, penal, endocervical, rectum, respiratory, and vaginal and tooth pocket. Non limiting examples of applications include eye infections, blepharitis, dry eye, inclusion conjunctivitis, glaucoma, inflammatory ocular conditions where bacterial infection or a risk of bacterial ocular infection exists, neuropathic atrophy (in diabetes), abrasions, injuries, wounds, bums, ulcers, pyoderma, furunculosis, granuloma inguinale, periodontitis, rosacea , post-operation infections and tissue reconstruction, trachoma, lymphogranuloma venereum, granuloma inquinale, acne, inflammation, sinusitis, neuro-protection, washing out, disinfectation, and stabilization of body cavities, at on around or in the site of an operation, which for example can provide multiple therapeutic effects, such as, inhibition of post operation adhesions, anti infection, neuro-protection.
[0194] Whether delivered as a foam, gel, ointment or suspension the active pharmaceutical tetracycline can be present by weight in the range of about 0.2% to about 20%, or at about 0.2%, at about 0.3%, at about 0.4%, at about 0.5%, at about 0.6%, at about 0.7%, at about 0.8%, at about 0.9%, at about 1%, at about 1.5%, at about 2%, at about 2.5%, at about 3%, at about 3.5%
at about 4%, at about 4.5%, at about 5%, at about 6%,at about 7%, at about 8%, at about 9%, at about 10%, at about 12%, or at about 14%, at about 16%, at about 18%, or at about 20%.
Tetracyclines and skin infections
at about 4%, at about 4.5%, at about 5%, at about 6%,at about 7%, at about 8%, at about 9%, at about 10%, at about 12%, or at about 14%, at about 16%, at about 18%, or at about 20%.
Tetracyclines and skin infections
[0195] Tetracyclines have been used in ophthalmic ointments for the prevention or treatment of infections of the eye caused by susceptible bacteria. Although minor skin infections and wounds usually heal without treatment, some minor skin wounds do not heal without therapy and it is impossible to determine at the time of injury which wounds will be self-healing. Therefore, some experts believe that, by reducing the number of superficial bacteria, topical anti-infectives are useful for preventing infection in minor skin injuries (e.g., cuts, scrapes, bums).
[0196] Tetracycline hydrochloride may be used topically in the treatment of inflammatory acne vulgaris. Tetracyclines are usually bacteriostatic in action, but may be bactericidal in high concentrations or against highly susceptible organisms.
[0197] Tetracyclines appear to inhibit protein synthesis in susceptible organisms primarily by reversibly binding to 30S ribosomal subunits, thereby inhibiting binding of aminoacyl transfer-RNA to those ribosomes. In addition, tetracyclines appear to reversibly bind to 50S ribosomal subunits. There is preliminary evidence that tetracyclines also alter cytoplasmic membranes of susceptible organisms resulting in leakage of nucleotides and other intracellular components from the cell. At high concentrations, tetracyclines also inhibit mammalian protein synthesis.
[0198] The exact mechanisms by which tetracyclines reduce lesions of acne vulgaris have not been fully elucidated; however, the effect appears to be partly the result of the antibacterial activity of the drugs. Following topical application to the skin of a 0.22%
solution of tetracycline hydrochloride in a vehicle containing n-decyl methyl sulfoxide (Topicycline ;
no longer commercially available in the US), the drug inhibits the growth of susceptible organisms (principally Propionibacterium acnes) on the surface of the skin and reduces the concentration of free fatty acids in sebum. The reduction in free fatty acids in sebum may be an indirect result of the inhibition of lipase-producing organisms which convert triglycerides into free fatty acids or may be a direct result of interference with lipase production in these organisms. Free fatty acids are comedogenic and are believed to be a possible cause of the inflammatory lesions (e.g., papules, pustules, nodules, cysts) of acne. However, other mechanisms also appear to be involved because clinical improvement of acne vulgaris with topical tetracyclines does not necessarily correspond with a reduction in the bacterial flora of the skin or a decrease in the free fatty acid content of sebum. (Martindale Electronic Version 2007).
Tetracyclines, solubility and stability
solution of tetracycline hydrochloride in a vehicle containing n-decyl methyl sulfoxide (Topicycline ;
no longer commercially available in the US), the drug inhibits the growth of susceptible organisms (principally Propionibacterium acnes) on the surface of the skin and reduces the concentration of free fatty acids in sebum. The reduction in free fatty acids in sebum may be an indirect result of the inhibition of lipase-producing organisms which convert triglycerides into free fatty acids or may be a direct result of interference with lipase production in these organisms. Free fatty acids are comedogenic and are believed to be a possible cause of the inflammatory lesions (e.g., papules, pustules, nodules, cysts) of acne. However, other mechanisms also appear to be involved because clinical improvement of acne vulgaris with topical tetracyclines does not necessarily correspond with a reduction in the bacterial flora of the skin or a decrease in the free fatty acid content of sebum. (Martindale Electronic Version 2007).
Tetracyclines, solubility and stability
[0199] Tetracyclines are known to be unstable in the presence of water, as well as numerous types of formulation excipients, such as protic solvents, various surfactants and certain oils. We surprisingly discovered that the inclusion of tetracyclines in a composition comprising a hydrophobic solvent and a foaming agent described herein results in a stable product, with extended stability of the tetracycline. In an embodiment a hydrophobic solvent is selected by (1) testing the solubility of said active agent in various hydrophobic solvents, (2) identifying those that do not solubilize the active agent followed by (3) inclusion in the composition of such solvents that do not solubilize the active agent. In certain embodiments the tetracycline is insoluble in the composition.
Doxycycline
Doxycycline
[0200] According to some embodiments, the tetracycline is doxycycline.
Doxycycline is a tetracycline antibiotic and also has anti-inflammatory and immunomodulatory effects.
Doxycycline is a semisynthetic tetracycline antibiotic derived from oxytetracycline. In addition to antimicrobial activity, the drug has anti-inflammatory and immunomodulatory effects. It is available as Doxycycline calcium, doxycycline hyclate and doxycycline monohydrate.
Doxycycline hyclate and doxycycline monohydrate occur as yellow, crystalline powders. The hyclate is soluble in water and slightly soluble in alcohol; the monohydrate is very slightly soluble in water and sparingly soluble in alcohol. Doxycycline calcium is formed in situ during the manufacturing process. Following reconstitution of doxycycline hyclate powder for IV
administration with sterile water for injection, solutions have a pH of 1.8-3.3.
Doxycycline is a tetracycline antibiotic and also has anti-inflammatory and immunomodulatory effects.
Doxycycline is a semisynthetic tetracycline antibiotic derived from oxytetracycline. In addition to antimicrobial activity, the drug has anti-inflammatory and immunomodulatory effects. It is available as Doxycycline calcium, doxycycline hyclate and doxycycline monohydrate.
Doxycycline hyclate and doxycycline monohydrate occur as yellow, crystalline powders. The hyclate is soluble in water and slightly soluble in alcohol; the monohydrate is very slightly soluble in water and sparingly soluble in alcohol. Doxycycline calcium is formed in situ during the manufacturing process. Following reconstitution of doxycycline hyclate powder for IV
administration with sterile water for injection, solutions have a pH of 1.8-3.3.
[0201] The mechanism(s) by which doxycycline reduces inflammatory lesions (papules and pustules) in patients has not been elucidated, but these effects may result at least in part from the anti-inflammatory actions of the drug; other mechanisms may be involved
[0202] Doxycycline is used for the treatment of rosacea treatment or prophylaxis of anthrax (including inhalational anthrax [postexposure]), treatment of presumed or confirmed rickettsial infections, including Rocky Mountain spotted fever (RMSF), fever, ehrlichiosis, and anaplasmosis, and for the treatment of Bartonella infections, for the treatment of brucellosis, for the treatment of Burkholderia Infections, Chlamydial Infections , Lymphogranuloma venereum Psittacosis, Ehrlichiosis and Anaplasmosis, Gonorrhea and Associated Infections, Epididymitis, Proctitis, Granuloma Inguinale (Donovanosis,) Legionella Infections, Leptospirosis, Lyme Disease, Prophylaxis of Lyme Disease, Erythema Migrans, Early Neurologic Lyme Disease, Lyme Carditis, or Borrelial Lymphocytoma, Lyme Arthritis, Malaria, and prevention, Mycobacterial Infections, Mycobacterium marinum Infections, Pelvic Inflammatory Disease, Parenteral Regimens, Plague, , pleural Effusion, Rickettsial Infections, Q
Fever, Syphilis, Tularemia, Treatment, Postexposure Prophylaxis
Fever, Syphilis, Tularemia, Treatment, Postexposure Prophylaxis
[0203] When reconstituted and diluted with 0.9% sodium chloride or 5%
dextrose, doxycycline hyclate IV solutions containing 0.1-1 mg of doxycycline per mL are stable for 48 hours at 25 C; when reconstituted and diluted with Ringer's, 10% invert sugar, Normosol-M in D5W, Normosol-R in D5W, Plasma-Lyte 56 in 5% dextrose, or Plasma-Lyte 148 in 5%
dextrose, doxycycline hyclate IV solutions containing 0.1-1 mg/mL are stable for 12 hours at room temperature. The manufacturer states that doxycycline hyclate solutions prepared with any of these infusion solutions are stable for 72 hours at 2-8 C when protected from direct sunlight and artificial light; however, after storage in this manner, infusion of these solutions must be completed within 12 hours Doxycycline hyclate IV solutions diluted to a concentration of 0.1-1 mg/mL with lactated Ringer's injection or 5% dextrose in lactated Ringer's injection must be infused within 6 hours to ensure stability. During infusion, all doxycycline hyclate IV solutions must be protected from direct sunlight. (Martindale 2007 Electronic Version).
Thus it can be seen that Doxycycline is not stable for more than short periods of a matter of hours.
dextrose, doxycycline hyclate IV solutions containing 0.1-1 mg of doxycycline per mL are stable for 48 hours at 25 C; when reconstituted and diluted with Ringer's, 10% invert sugar, Normosol-M in D5W, Normosol-R in D5W, Plasma-Lyte 56 in 5% dextrose, or Plasma-Lyte 148 in 5%
dextrose, doxycycline hyclate IV solutions containing 0.1-1 mg/mL are stable for 12 hours at room temperature. The manufacturer states that doxycycline hyclate solutions prepared with any of these infusion solutions are stable for 72 hours at 2-8 C when protected from direct sunlight and artificial light; however, after storage in this manner, infusion of these solutions must be completed within 12 hours Doxycycline hyclate IV solutions diluted to a concentration of 0.1-1 mg/mL with lactated Ringer's injection or 5% dextrose in lactated Ringer's injection must be infused within 6 hours to ensure stability. During infusion, all doxycycline hyclate IV solutions must be protected from direct sunlight. (Martindale 2007 Electronic Version).
Thus it can be seen that Doxycycline is not stable for more than short periods of a matter of hours.
[0204] Preparations of doxycycline hyclate have an acid pH and incompatibility may reasonably be expected with alkaline preparations or with drugs unstable at low pH.
[0205] Doxycycline is more active than tetracycline against many bacterial species including Streptococcus pyogenes, enterococci, Nocardia spp., and various anaerobes.
Cross-resistance is common although some tetracycline-resistant Staphylococcus aureus respond to doxycycline.
Doxycycline is also more active against protozoa, particularly Plasmodium spp.
Cross-resistance is common although some tetracycline-resistant Staphylococcus aureus respond to doxycycline.
Doxycycline is also more active against protozoa, particularly Plasmodium spp.
[0206] Doxycycline is a tetracycline derivative with uses similar to those of tetracycline. It may sometimes be preferred to other tetracyclines in the treatment of susceptible infections because of its fairly reliable absorption and its long half-life that permits less frequent (often once daily) dosing. It also has the advantage that it can be given (with care) to patients with renal impairment. However, relatively high doses may need to be given for urinary-tract infections because of its low renal excretion.
[0207] For relapsing fever and louse-borne typhus, for the prophylaxis of leptospirosis , for periodontiti, for Lymphatic filariasis, for Musculoskeletal and joint disorders and for the treatment of acne.
Minocycline
Minocycline
[0208] According to some embodiments, the tetracycline is minocycline.
Minocycline hydrochloride is a semisynthetic tetracycline antibiotic derived from tetracycline. The drug is usually bacteriostatic in action; it exerts its antimicrobial activity by inhibiting protein synthesis.
It is a yellow crystalline powder that is sparingly soluble in water; slightly soluble in alcohol;
practically insoluble in chloroform and in ether; soluble in solutions of alkali hydroxides and carbonates. pH of a solution in water containing the equivalent of minocycline I% is between 3.5 and 4.5. Preparations of minocycline hydrochloride have an acid pH and incompatibility may reasonably be expected with alkaline preparations or with drugs unstable at low pH.
Minocycline hydrochloride is a semisynthetic tetracycline antibiotic derived from tetracycline. The drug is usually bacteriostatic in action; it exerts its antimicrobial activity by inhibiting protein synthesis.
It is a yellow crystalline powder that is sparingly soluble in water; slightly soluble in alcohol;
practically insoluble in chloroform and in ether; soluble in solutions of alkali hydroxides and carbonates. pH of a solution in water containing the equivalent of minocycline I% is between 3.5 and 4.5. Preparations of minocycline hydrochloride have an acid pH and incompatibility may reasonably be expected with alkaline preparations or with drugs unstable at low pH.
[0209] Minocycle is highly sensitive and should be stored in airtight containers and protected from light to prevent degradation. Therefore use in foamable formulations stored in airtight sealed containers under pressure with propellant may contribute to preserving stability subject to selection of compatible canisters and accessories.
[0210] Photosensitivity, manifested as an exaggerated sunburn reaction on areas of the body exposed to direct sunlight or ultraviolet light, has occurred with tetracyclines and Minocycline has been associated with pigmentation of the skin and other tissues.
[0211] Minocycline has a spectrum of activity and mode of action similar to that of tetracycline but it is more active against many species including Staphylococcus aureus, streptococci, Neisseria meningitidis, various enterobacteria, Acinetobacter, Bacteroides, Haemophilus, Nocardia, and some mycobacteria, including M. leprae. Partial cross-resistance exists between minocycline and other tetracyclines but some strains resistant to other drugs of the group remain sensitive to minocycline, perhaps because of better cell-wall penetration.
Minocycline is a tetracycline derivative with uses similar to those of tetracycline. It is also a component of multidrug regimens for the treatment of leprosy and has been used in the prophylaxis of meningococcal infection to eliminate the carrier state, but the high incidence of vestibular disturbances means that it is not the drug of choice for the latter. It has neuroprotective properties. It is being investigated for motor neurone disease, for the management of Huntington's chorea. It is used in the treatment of rheumatoid arthritis and in the treatment of various skin disorders, including acne.
Steroids
Minocycline is a tetracycline derivative with uses similar to those of tetracycline. It is also a component of multidrug regimens for the treatment of leprosy and has been used in the prophylaxis of meningococcal infection to eliminate the carrier state, but the high incidence of vestibular disturbances means that it is not the drug of choice for the latter. It has neuroprotective properties. It is being investigated for motor neurone disease, for the management of Huntington's chorea. It is used in the treatment of rheumatoid arthritis and in the treatment of various skin disorders, including acne.
Steroids
[0212] In an embodiment, the active agent is a steroid. In certain embodiments the steroid is a corticosteroid, including but not limited to, hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethsone dipropionate, clobetasol valemate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylester, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone and the balance of its esters, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortmate, mepreddisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate, triamcinolone, as well as analogs, derivatives, salts, ions and complexes thereof.
[0213] In certain embodiments, the steroid is a hormone or a vitamin, as exemplified by pregnane, cholestane, ergostane, aldosterone, androsterone, calcidiol, calciol, calcitriol, calcipotriol, clomegestone, cholesterol, corticosterone, cortisol, cortisone, dihydrotestosterone, ergosterol, estradiol, estriol, estrone, ethinylestradiol, fusidic acid, lanosterol, prednisolone, prednisone, progesterone, spironolactone, timobesone and testosterone, as well as analogs, derivatives, salts, ions and complexes thereof. For substances like calcitriol, very low amounts such as about 0.0001% to about 0.005% by weight of foam formulation or gel or ointment or suspension, or about 0.0001%, about 0.0002%, about 0.0003%, about 0.0004%, about 0.0005%, about 0.0006%, about 0.0007%, about 0.0008%, about 0.0009%, about 0.001%, about 0.0011%, about 0.0012%, about 0.0013%, about 0.0014%, about 0.0015%, about 0.0016%, about 0.0017%, about 0.0018%, about 0.0019%, about 0.002%, about 0.003%, about 0.004%, about 0.005% by weight are effective. In some embodiments the active pharmaceutical agent is delivered by more than one route, for example, topically and body cavity.
[0214] In an embodiment, the steroid is mometasone furoate. In certain embodiments it can be used topically to treat psoriasis and dermatitis. In certain other embodiments it can be applied in nasal administration to treat disorders, such as, allergic rhinitis and asthma.
NSAID
NSAID
[0215] In an embodiment, the active agent is a non-steroidal anti-inflammatory agent. In the context a nonsteroidal antiinflammatory agent (also termed herein "NSAID") is a pharmaceutically active compound, other than a corticosteroid, which affects the immune system in a fashion that results in a reduction, inhibition, prevention, amelioration or prevention of an inflammatory process and/or the symptoms of inflammation and or the production pro-inflammatory cytokines and other pro-inflammatory mediators, thereby treating or preventing a disease that involves inflammation.
[0216] In one or more embodiments, the NSAID is an inhibitor of the cyclooxygenase (COX) enzyme. Two forms of cyclooxygenase are known today: the constitutive cyclooxygenase (COX-1); and the inducible cyclooxygenase (COX-2), which is pro-inflammatory. Thus, in one or more embodiments, the NSAID is selected from the group consisting of a COX-1 inhibitor, a COX-2 inhibitor or a non-selective NSAID, which simultaneously inhibits both COX-1 and COX-2.
[0217] In one or more embodiments, the NSAID is salicylic acid a salicylic acid derivatives.
Exemplary salicylic acid derivative include, in a non limiting fashion, aspirin, sodium salicylate, choline magnesium trislicylate, salsalate, diflunisal, salicylsalicylic acid, sulfasalazine, olsalazine, esters of salicylic acid with a carboxylic acid, esters of salicylic acid with a dicarboxylic acid, esters of salicylic acid with a fatty acid, esters of salicylic acid with a hydroxyl fatty acid, esters of salicylic acid with an essential fatty acid, esters of salicylic acid with a polycarboxylic acid, and any compound wherein salicylic acid is linked to an organic moiety through a covalent bond.
Exemplary salicylic acid derivative include, in a non limiting fashion, aspirin, sodium salicylate, choline magnesium trislicylate, salsalate, diflunisal, salicylsalicylic acid, sulfasalazine, olsalazine, esters of salicylic acid with a carboxylic acid, esters of salicylic acid with a dicarboxylic acid, esters of salicylic acid with a fatty acid, esters of salicylic acid with a hydroxyl fatty acid, esters of salicylic acid with an essential fatty acid, esters of salicylic acid with a polycarboxylic acid, and any compound wherein salicylic acid is linked to an organic moiety through a covalent bond.
[0218] In one or more embodiments, the NSAID is para-aminophenol (e.g., acetaminophen) and salts and derivatives thereof.
[0219] In one or more embodiments, the NSAID is an indole or an indole -acetic acid derivative (e.g., indomethacin, sulindac, etodolac) and salts and derivatives thereof.
[0220] In one or more embodiments, the NSAID is an aryl acetic acids (e.g., tolmetin, diclofenac, ketorolac) and salts and derivatives thereof.
[0221] In one or more embodiments, the NSAID is an arylpropionic acid and salts and derivatives thereof. Exemplary arylpropionic acid derivative include, in a non limiting fashion, are ibuprofen, naproxen, flubiprofen, ketoprofen, fenoprofen, oxaprozin.
[0222] In one or more embodiments, the NSAID is anthranilic acids or an anthranilic acid derivative, also termed "fenamates" (e.g., mefenamic acid, meclofenamic acid) and salts and derivatives thereof.
[0223] In one or more embodiments, the NSAID is selected from the group of enolic acids, enolic acid salts, enolic acid esters, amides, anhydrides and salts and derivatives thereof. Non-limiting examples of enolic acid derivatives include oxicams (piroxicam, tenoxicam) and pyrazolidinediones (phenylbutazone, oxyphenthratrazone)
[0224] Yet, in additional embodiments, the NSAID is an alkanone (e.g., nabumetone).
[0225] Selective COX-2 Inhibitors include, in an exemplary manner diaryl-substituted furanones (e.g., Rofecoxib); diaryl-substituted pyrazoles (e.g., Celecoxib);
indole acetic acids (e.g., Etodolac); and sulfonanilides (e.g., Nimesulide) and salts and derivatives thereof.
Local anesthetic agents
indole acetic acids (e.g., Etodolac); and sulfonanilides (e.g., Nimesulide) and salts and derivatives thereof.
Local anesthetic agents
[0226] In an embodiment, the active agent is a local anesthetic agent. Without limiting the scope, the anesthetic agent can be selected from the group consisting of benzocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine, pramoxine, phenol, any pharmaceutically acceptable salts thereof and mixtures of such anesthetic agents. Any mixture of synergistically beneficial anesthetic agents is contemplated.
Keratolytically active agents
Keratolytically active agents
[0227] A keratolytic agent may be included as an active agent of a foamable composition.
The term "keratolytically active agent" as used herein includes a compound that loosens and removes the stratum corneum of the skin, or alters the structure of the keratin layers of skin.
Keratolytically active agents are used in the treatment of dermatological disorders that involve dry skin, hyperkeratinization (such as psoriasis), skin itching (such as xerosis), acne and rosacea.
The term "keratolytically active agent" as used herein includes a compound that loosens and removes the stratum corneum of the skin, or alters the structure of the keratin layers of skin.
Keratolytically active agents are used in the treatment of dermatological disorders that involve dry skin, hyperkeratinization (such as psoriasis), skin itching (such as xerosis), acne and rosacea.
[0228] Suitable keratolytically active agents include phenol and substituted phenolic compounds. Such compounds are known to dissolve and loosen the intracellular matrix of the hyperkeratinized tissue. As such, they are used in the treatment of dermatological disorders.
Dihydroxybenzene and derivatives thereof have been recognized as potent keratolytic agents.
Resorcinol (m-dihydroxybenzene) and derivatives thereof are used in anti-acne preparations. In addition to hydroquinone (p-dihydroxybenzene) having anti-pigmentation properties, hydroquinone is also known to be keratolytic. These compounds also exhibit antiseptic properties. Cresols also possess bactericidal and keratolytic properties.
Dihydroxybenzene and derivatives thereof have been recognized as potent keratolytic agents.
Resorcinol (m-dihydroxybenzene) and derivatives thereof are used in anti-acne preparations. In addition to hydroquinone (p-dihydroxybenzene) having anti-pigmentation properties, hydroquinone is also known to be keratolytic. These compounds also exhibit antiseptic properties. Cresols also possess bactericidal and keratolytic properties.
[0229] Vitamin A and vitamin A derivatives, also termed herein "retinoids", such as retinoic acid, isoretinoic acid, retinol and retinal, as well as adapalene, tazarotene, isotretinoin, acitretin and additional retinoids known in the art of pharmaceuticals and cosmetics are another class of keratolytically active agents.
[0230] Another group of keratolytically active agents include alpha-hydroxy acids, such as lactic acid and glycolic acid and their respective salts and derivatives; and beta-hydroxy acids, such as salicylic acid (o-hydroxybenzoic acid) and salicylic acid salts and pharmaceutically acceptable derivatives.
[0231] Another class of keratolytically active agents includes urea and urea derivatives.
Immunomodulators
Immunomodulators
[0232] In an embodiment, the active agent is an immunomodulator.
Immunomodulators are chemically or biologically-derived agents that modify the immune response or the functioning of the immune system. Immunomodulators suitable for use according to the present invention include, among other options, cyclic peptides, such as cyclosporine, tacrolimus, tresperimus, pimecrolimus, sirolimus, verolimus, laflunimus, laquinimod and imiquimod, as well as analogs, derivatives, salts, ions and complexes thereof. Such compounds, delivered in the foam, are especially advantageous in skin disorders such as psoriasis, eczema and atopic dermatitis, where the large skin areas are to be treated.
Retinoids
Immunomodulators are chemically or biologically-derived agents that modify the immune response or the functioning of the immune system. Immunomodulators suitable for use according to the present invention include, among other options, cyclic peptides, such as cyclosporine, tacrolimus, tresperimus, pimecrolimus, sirolimus, verolimus, laflunimus, laquinimod and imiquimod, as well as analogs, derivatives, salts, ions and complexes thereof. Such compounds, delivered in the foam, are especially advantageous in skin disorders such as psoriasis, eczema and atopic dermatitis, where the large skin areas are to be treated.
Retinoids
[0233] In an embodiment, the active agent is a retinoid. Retinoids suitable for use according to the present invention include, among other options, retinol, retinal, retinoic acid, isotretinoin, tazarotene, adapalene, 13-cis-retinoic acid, acitretin all-trans beta carotene, alpha carotene, lycopene, 9-cis-beta-carotene, lutein and zeaxanthin, as well as any additional retinoids known in the art of pharmaceuticals and cosmetics; and analogs, derivatives, salts, ions and complexes thereof.
Anti-acne and anti-rosacea active agents
Anti-acne and anti-rosacea active agents
[0234] In an embodiment, the active agent is an anti-acne or an anti-rosacea agent. The anti-acne agent can be selected from the group consisting of resorcinol, sulfur, salicylic acid and salicylates, alpha-hydroxy acids, nonsteroidal anti-inflammatory agents, benzoyl peroxide, retinoic acid, isoretinoic acid and other retinoid compounds, adapalene, tazarotene, azelaic acid and azelaic acid derivatives, antibiotic agents, such as erythromycin and clyndamycin, coal tar, zinc salts and complexes, and combinations thereof, in a therapeutically effective concentration.
Antipsoriasis agents
Antipsoriasis agents
[0235] In an embodiment, the active agent is an anti-psoriasis agent. Such anti-psoriasis agents can be selected, among other options, from the group of keratolytically-active agents, salicylic acid, coal tar, anthralin, corticosteroids, vitamin D and derivatives and analogs thereof, including vitamin D3 analogs such as calcitriol, calcipotriol; retinoids, and photodymamic therapy agents.
Antiinfective agents
Antiinfective agents
[0236] In an embodiment, the active agent is an anti-infective agent. Such anti-infective agent can be selected from the group of an antibiotic agent, an antibacterial agent, an antifungal agent, an agent that controls yeast, an antiviral agent and an antiparasitic agent. Exemplary antiinfective agents are exemplified by beta-lactam antibiotic, an aminoglycoside, an ansa-type antibiotic, an anthraquinone, an azole, metronidazole, an antibiotic glycopeptide, a macrolide, erythromycin, clindamycin, an antibiotic nucleoside, an antibiotic peptide, polymyxin B, an antibiotic polyene, an antibiotic polyether, an antibiotic quinolone, an antibiotic steroid, fucidic acid, mupirocin, chloramphenicol, a sulfonamide, tetracycline, an antibiotic metal, silver, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium, an oxidizing agent, iodine, iodate, a periodate, a hypochlorite, a permanganate, a substance that release free radicals and/or active oxygen, a cationic antimicrobial agent, a quaternary ammonium compound, a biguanide, chlorohexidine, a triguanide, a bisbiguanide, a polymeric biguanide and a naturally occurring antibiotic compound, as well as analogs, derivatives, salts, ions and complexes thereof.
The foamable composition essential ingredients as active agents
The foamable composition essential ingredients as active agents
[0237] In certain embodiments, a hydrophobic solvent possesses therapeutic properties on its own and therefore, it can be regarded as "active agent." For example, some essential oils kill microorganisms and can be effective in the treatment or prevention of conditions that involve microbial infection, such as bacterial, fungal and viral conditions.
Additionally, the occlusive effect of hydrophobic solvents is useful for the treatment of conditions which involve damaged skin, such as psoriasis or atopic dermatitis. The combination of a hydrophobic solvent and a therapeutically effective fatty alcohol or fatty acid may afford a synergistic beneficial effect in conditions characterized, for example, by infection and/or inflammation.
Combination of active agents
Additionally, the occlusive effect of hydrophobic solvents is useful for the treatment of conditions which involve damaged skin, such as psoriasis or atopic dermatitis. The combination of a hydrophobic solvent and a therapeutically effective fatty alcohol or fatty acid may afford a synergistic beneficial effect in conditions characterized, for example, by infection and/or inflammation.
Combination of active agents
[0238] Several disorders involve a combination of more than one etiological factor; and therefore, the use of more that one active agents is advantageous. For example, psoriasis involves excessive cell proliferation and inadequate cell differentiation as well as inflammation. Atopic dermatitis involves keratinocyte growth abnormality, skin dryness and inflammation. Bacterial, fungal and viral infections involve pathogen colonization at the affected site and inflammation.
Hence, in many cases, the inclusion of a combination of active agents in the foamable pharmaceutical composition can be desirable. Thus, in one or more embodiments, the foamable composition further includes at least two active agents, in a therapeutically effective concentration.
Hence, in many cases, the inclusion of a combination of active agents in the foamable pharmaceutical composition can be desirable. Thus, in one or more embodiments, the foamable composition further includes at least two active agents, in a therapeutically effective concentration.
[0239] In an embodiment one of the active agents is a vitamin, a vitamin derivative or analogue thereof. In a preferred embodiment the vitamin, vitamin derivative or analogue thereof is oil soluble.
Microsponges
Microsponges
[0240] Microsponges (or microspheres) are rigid, porous and spongelike round microscopic particles of cross-linked polymer beads (e.g., polystyrene or copolymers thereof), each defining a substantially noncollapsible pore network. Microsponges can be loaded with an active ingredient and can provide a controlled time release of the active ingredient to skin or to a mucosal membrane upon application of the formulation. The slow release is intended to reduce irritation by the active ingredient. Microsponge delivery technology was developed by Advanced Polymer Systems. In one or more embodiments the composition comprises one or more active agents loaded into Microponges with a waterless carrier described herein, which may also comprise a modulating agent.
Fields of Applications
Fields of Applications
[0241] The foamable carrier of the present disclosure is suitable for treating any inflicted surface. In one or more embodiments, foamable carrier is suitable for administration to the skin, a body surface, a body cavity or mucosal surface, e.g., the cavity and/or the mucosa of the nose, mouth, eye, respiratory system, vagina, urethra, rectum and the ear canal (severally and interchangeably termed herein "target site").
[0242] The foamable carrier of the present disclosure is also suitable for preventing a disorder or disease prior to its onset. The foamble carrier comprising for example a tetracycline may be applied to a body surface or a body cavity to try and prevent apoptosis, a disorder or disease prior to onset thereof. For example, prior to an anticipated inflammatory reaction or risk thereof , or prior to an anticipated onset of apoptosis or a risk thereof, or prior to an anticipated onset of inflammatory cytokines or risk thereof, prior to a medical procedure requiring intervention such as chemo therapy; radiotherapy, photodynamic therapy, laser therapy, etc. An simple example of prevention use, such as in the case of an eye infection say of one eye, is where the foam comprising a tetracycline (or the formulation prior to addition of propellant) is applied to the skin surface surrounding both eyes so as to reduce the risk of the infection spreading to the second eye or alternatively or additionally to the eye itself.
[0243] According to another embodiment a none limiting list of disorders where a tetracycline antibiotic might be used to prevent a disease or disorder is includes prophylaxis of gonococcal and chlamydial ophthalmia, neonatal conjunctivitis, periodontal disease, postoperative tetracycline , prophylaxis in pregnancy termination, for prevention of skin rash/acneiform skin eruption during cancer therapy, intraoperative topical tetracycline sclerotherapy following mastectomy for prevention of postoperative mastectomy seromas etc..
[0244] By selecting a suitable active agent, or a combination of at least two active agents, the foamable composition of the present disclosure is useful in treating an animal or a human patient having any one of a variety of dermatological diseases or disorders; in alleviating such diseases or disorders; or where such agent or agents have shown proficiency in preventative therapy in preventing such diseases or disorders , including but not limited to abscess, acne, acne conglobata, acne fulminans, acne vulgaris, acne scars, acute febrile neutrophilic dermatosis, acute lymphangitis, allergic contact dermatitis, alopecia, athlete's foot, atopic dermatitis, bacterial skin infections, baldness, basal cell carcinoma, blisters, bromhidrosis, bullous pemphigoid, burn, calluses candidiasis, carbuncles, cellulitis, chemical burns, chicken pox, cholesteatoma, cholinergic urticaria, chronic effects of sunlight, cold sores, cold urticaria, comedones, corns, creeping eruption, cutaneous abscess, cutaneous larva migrans, cutaneous myiasis, dark spots, delusional parasitosis, Dercum disease, dermatitis, dermatitis herpetiformis, dermatological pain, dermatological inflammation, dermographism, dermatophytoses, drug eruptions and reactions, dyshidrotic eczema, ectodermal dysplasia, eczema, ecthyma, epidermoid cyst, epidermal necrolysis, erysipelas, erysipelas, erythrasma, exfoliative dermatitis, erythema multiforme, erythema nodosum, folliculitis, fungal nail infections, fungal skin infections, furuncles, gangrene, genital herpes, granuloma annulare, head lice, hidradenitis suppurativa, hives, folliculitis, hirsutism, hyperhidrosis, hypohidrosis, ichthyosis, impetigo, inflammatory acne, ingrown nails, intertrigo, irritant contact dermatitis, ischemic necrosis, itching, jock itch, Kaposi's sarcoma, keratosis pilaris, lichen simplex chronicus, lichen planus, lichen sclerosus, lymphadenitis, lymphadenitis, lymphangitis, malignant melanoma, mastocytosis, measles, melanoma, melanoma, miliaria, moles, molluscum contagiosum, MRSA, necrotizing subcutaneous infection, necrotizing fasciitis, necrotizing myositis, nodular papulopustular acne, non-inflammatory acne, nummular dermatitis, oral herpes, panniculitis, parapsoriasis paronychia, parasitic skin infections, pemphigus, photo-allergy, photo-damage, photo-irritation, photosensitivity, papules, pediculosis, perioral dermatitis, pimples, pityriasis rosea, pityriasis Lichenoides, pityriasis rosea, pityriasis rubra pilaris, poison ivy, poison oak post-operative or post-surgical skin conditions, pressure ulcers, pressure urticaria, pruritis, pseudofolliculitis barbae, psoriasis, PUPPP, purpura, pustules, pyogenic granuloma, rash, ringworm, rosacea, roseola, rubella, scabies, scalded skin syndrome, scarring, scleroderma, sebaceous cyst, seborrheic dermatitis, seborrheic keratosis, shingles, skin aging, skin cancer, skin neoplasia, skin neoplasms, skin rash, skin ulcers, squamous cell carcinoma, staphylococcal scalded skin syndrome, stasis dermatitis, Stevens-Johnson syndrome, sunburn, sun spots, thermal burns, tinea corporis, tinea cruris, tinea pedis, tinea versicolor, toxic epidermal necrolysis, trauma or injury to the skin, varicella zoster virus, vitamin D deficiency, viral skin infections, vitiligo, warts, water hives, wrinkles, xerosis, yeast skin infections and zoster..
[0245] Likewise, the foamable composition of the present disclosure is suitable for preventing or treating or alleviating a disorder of a body cavity or mucosal surface, e.g., the mucosa of the nose, mouth, eye, ear, respiratory system, vagina, urethra, or rectum. Non limiting examples of such conditions include chlamydia infection, gonorrhea infection, hepatitis B, herpes, HIV/AIDS, human papillomavirus (HPV), genital warts, bacterial vaginosis, candidiasis, chancroid, granuloma Inguinale, lymphogranloma venereum, mucopurulent cervicitis (MPC), molluscum contagiosum, nongonococcal urethritis (NGU), trichomoniasis, vulvar disorders, vulvodynia, vulvar pain, yeast infection, vulvar dystrophy, vulvar intraepithelial neoplasia (VIN), contact dermatitis, pelvic inflammation, endometritis, salpingitis, oophoritis, genital cancer, cancer of the cervix, cancer of the vulva, cancer of the vagina, vaginal dryness, dyspareunia, anal and rectal disease, anal abscess/fistula, anal cancer, anal fissure, anal warts, Crohn's disease, hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation, polyps of the colon and rectum.
[0246] In an embodiment of the present disclosure, the composition is useful for the treatment of an infection. In one or more embodiments, the composition is suitable for the treatment of an infection, selected from the group of a bacterial infection, a fungal infection, a yeast infection, a viral infection and a parasitic infection.
[0247] In an embodiment of the present disclosure, the composition is useful for the treatment of wound, ulcer and burn. This use is particularly important since the composition of the present disclosure creates a thin, semi-occlusive layer, which coats the damaged tissue, while allowing exudates to be released from the tissue.
[0248] The composition of the present disclosure is also suitable for administering a hormone to the skin or to a mucosal membrane or to a body cavity, in order to deliver the hormone into the tissue of the target organ, in any disorder that responds to treatment with a hormone.
[0249] In one embodiment the disorder is an inflammation, skin inflammation, acne, rosacea, actinic keratosis, skin cancer, a local pain, joint pain and ostheoarthritis; the active agent is a nonsteroidal anti-inflammatory drug, given at a therapeutically effective concentration.
[0250] In light of the hygroscopic nature of the composition, it is further suitable for the treatment and prevention of post-surgical adhesions. Adhesions are scars that form abnormal connections between tissue surfaces. Post-surgical adhesion formation is a natural consequence of surgery, resulting when tissue repairs itself following incision, cauterization, suturing, or other means of trauma. When comprising appropriate protective agents, the foam is suitable for the treatment or prevention of post surgical adhesions. The use of foam is particularly advantageous because foam can expand in the body cavity and penetrate into hidden areas that cannot be reached by any other alternative means of administration.
Cosmetic use
Cosmetic use
[0251] In one or more embodiments, the composition may be used for cosmetic use. For example it may be used as part of a cosmetic formulation to prevent a cosmetic disorder or to improve the skin. Alternatively it may be used with cosmetic effect for example as a cosmetic remover. It can be dispensed in small quantities as a foam targeted to a surface and applied locally with mechanical force causing the foam to break.
Route of Administration
Route of Administration
[0252] The formulations disclosed herein can be applied to the target site as a foam. In one or more alternative embodiments the formulations are prepared without propellant and are applied as a gel or ointment, for example, with the tetracycline as a suspension.
Application can be hourly, 2 hourly, 3 hourly, four hourly, six hourly or eight hourly, twelve hourly, daily, alternate-day or intermittent, as necessary. For reasons of compliance less frequent applications, where possible are preferable such as twice -daily or daily single applications. In cases where prolonged or long term treatment is required a higher initial dose is provided followed by a gradual reduction to a lower maintenance dose, which can be increased if further outbreaks occur.
Application can be hourly, 2 hourly, 3 hourly, four hourly, six hourly or eight hourly, twelve hourly, daily, alternate-day or intermittent, as necessary. For reasons of compliance less frequent applications, where possible are preferable such as twice -daily or daily single applications. In cases where prolonged or long term treatment is required a higher initial dose is provided followed by a gradual reduction to a lower maintenance dose, which can be increased if further outbreaks occur.
[0253] The formulations are suitable for administration directly or indirectly to an inflicted area, in need of treatment, through the following routes of administration:
1. Topical administration: for local effect, it is applied directly where its action is desired;
2. Enteral: when the desired effect is systemic (non-local), it is given via the digestive tract;
and 3. Parenteral: when the desired effect is systemic, it is given by other routes than the digestive tract
1. Topical administration: for local effect, it is applied directly where its action is desired;
2. Enteral: when the desired effect is systemic (non-local), it is given via the digestive tract;
and 3. Parenteral: when the desired effect is systemic, it is given by other routes than the digestive tract
[0254] The following list more specifically exemplifies some routes of administration.
1. Topical
1. Topical
[0255] Topical administration is any form of administration that reaches a body organ topically, such as epicutaneous administration (application onto the skin), inhalation, enema, eye drops (onto the conjunctiva), ear drops, intranasal (into the nose) and vaginal.
[0256] Exemplary dosage forms that are suitable for topical administration of the stable tetracycline formulations include cream, gel, liniment, lotion, ointment, paste, spray, foam, mousse, lacquer (e.g., for nail treatment) and transdermal patch.
Additionally, topical vaginal dosage forms may include a douche, an intrauterine device, a pessary (vaginal suppository), a vaginal ring and a vaginal tablet. Rectal dosage forms include enema and suppositories. Inhaled dosage forms include aerosol inhalers, metered dose inhalers and solutions for nebulizer.
Ophthalmic dosage forms include eye drop (solution or suspension), ophthalmic gel and ophthalmic ointment. In a preferred embodiment the dosage form is a foam that is thermally stable and breakable under shear force but is not "quick breaking" which allows comfortable application and well directed administration to the target area.
2. Enteral
Additionally, topical vaginal dosage forms may include a douche, an intrauterine device, a pessary (vaginal suppository), a vaginal ring and a vaginal tablet. Rectal dosage forms include enema and suppositories. Inhaled dosage forms include aerosol inhalers, metered dose inhalers and solutions for nebulizer.
Ophthalmic dosage forms include eye drop (solution or suspension), ophthalmic gel and ophthalmic ointment. In a preferred embodiment the dosage form is a foam that is thermally stable and breakable under shear force but is not "quick breaking" which allows comfortable application and well directed administration to the target area.
2. Enteral
[0257] Enteral is any form of administration that involves any part of the gastrointestinal tract by mouth (orally), as buccal or sublingual tablets, capsules, suspensions, solutions, powder or drops; by gastric feeding tube, duodenal feeding tube, or gastrostomy; and rectally, in suppository or enema form.
3. Parenteral by injection or infusion
3. Parenteral by injection or infusion
[0258] Intravenous (into a vein); intraarterial (into an artery);
intramuscular (into a muscle);
intracardiac (into the heart); subcutaneous (under the skin); intraosseous infusion (into the bone marrow); intradermal, (into the skin itself); intrathecal (into the spinal canal); and intraperitoneal (into the peritoneum).
4. Other parenteral
intramuscular (into a muscle);
intracardiac (into the heart); subcutaneous (under the skin); intraosseous infusion (into the bone marrow); intradermal, (into the skin itself); intrathecal (into the spinal canal); and intraperitoneal (into the peritoneum).
4. Other parenteral
[0259] Transdermal (diffusion through the intact skin); transmucosal (diffusion through a mucous membrane), e.g. insufflation (snorting), sublingual, buccal (absorbed through cheek near gumline) and vaginal; and inhalational; epidural (synonym: peridural) (injection or infusion into the epidural space); and intravitreal.
EXAMPLES
EXAMPLES
[0260] The invention is described with reference to the following examples, in a non-limiting manner. The following examples exemplify the compositions and methods described herein. The examples are for the purposes of illustration only and are not intended to be limiting.
Many variations will suggest themselves and are within the full intended scope.
Example 1 - General Manufacturing Procedures
Many variations will suggest themselves and are within the full intended scope.
Example 1 - General Manufacturing Procedures
[0261] The following procedures are used to produce foam samples described in the examples below, in which only the steps relevant to each formulation are performed depending on the type and nature of ingredients used.
[0262] Step 1: Hydrophobic solvents are heated to 60-70 C.
[0263] Step 2: Waxes (and any fatty alcohols, if at all present, fatty acids, if at all present, or surfactants, if at all present) are added to the hydrophobic solvent and the formulation is mixed until complete melting.
[0264] Step 3: The formulation is cooled down to 30-40 C, active ingredients, if present, are added and the formulation is mixed until homogeneity is obtained.
[0265] Step 4: The formulation is cooled down to room temperature under mixing and packaged into suitable containers.
Materials Table 1 - Exemplary possible ingredients suitable for the production of foamable compositions disclosed herein. Equivalent materials from other manufacturers can also be used satisfactorily.
Chemical Name Function Commercial Name Supplier Beeswax white Foam adjuvant Beeswax white Henry Lamotte Benzoyl Peroxide Active agent Benzoyl Peroxide Spectrum C12-15 Alkyl Benzoate Solvent C12-15 Alkyl Benzoate Degussa Calcitriol Active agent Calcitriol Solvay Pharmaceutical Capric/caprylic triglycerides Solvent Captex 355 Abitec Cyclomethicone-5 Solvent ST-cyclomethicone-5 Dow Heavy Mineral Oil Solvent Paraffin oil liquid heavy Gadot Hydrogenated castor oil Foam adjuvant Cutina HR Cognis Isopropyl myristate Solvent Isopropyl Myristate Ph. Cognis Isopropyl palmitate Solvent Isopropyl Palmitate Cognis Lidocaine Active agent Lidocaine Sigma Light Mineral Oil Solvent Pioner 2076P Hansen & Rosenthal Minocycline HCl Active agent Minocycline HCl Hovione Mometasone Furoate Active agent Mometasone Furoate Sicor de Mexico Octyldodecanol Solvent Eutanol G Cognis Paraffin wax 42-44 Wax Paraffin 42-44 Merck Paraffin wax 51-53 Wax Paraffin 51-53 Merck Paraffin wax 58-62 Wax Paraffin 58-62 Merck PPG 15 stearyl ether Solvent Arlamol E Uniqema Propane/Isobutane/Butane (20:78:2) Propellant A-46 Aeropres Propane/Isobutane/Butane (55:18:27) Propellant AP-70 Aeropres Tetrafluoroethane Propellant Dymel 134a DuPont
Materials Table 1 - Exemplary possible ingredients suitable for the production of foamable compositions disclosed herein. Equivalent materials from other manufacturers can also be used satisfactorily.
Chemical Name Function Commercial Name Supplier Beeswax white Foam adjuvant Beeswax white Henry Lamotte Benzoyl Peroxide Active agent Benzoyl Peroxide Spectrum C12-15 Alkyl Benzoate Solvent C12-15 Alkyl Benzoate Degussa Calcitriol Active agent Calcitriol Solvay Pharmaceutical Capric/caprylic triglycerides Solvent Captex 355 Abitec Cyclomethicone-5 Solvent ST-cyclomethicone-5 Dow Heavy Mineral Oil Solvent Paraffin oil liquid heavy Gadot Hydrogenated castor oil Foam adjuvant Cutina HR Cognis Isopropyl myristate Solvent Isopropyl Myristate Ph. Cognis Isopropyl palmitate Solvent Isopropyl Palmitate Cognis Lidocaine Active agent Lidocaine Sigma Light Mineral Oil Solvent Pioner 2076P Hansen & Rosenthal Minocycline HCl Active agent Minocycline HCl Hovione Mometasone Furoate Active agent Mometasone Furoate Sicor de Mexico Octyldodecanol Solvent Eutanol G Cognis Paraffin wax 42-44 Wax Paraffin 42-44 Merck Paraffin wax 51-53 Wax Paraffin 51-53 Merck Paraffin wax 58-62 Wax Paraffin 58-62 Merck PPG 15 stearyl ether Solvent Arlamol E Uniqema Propane/Isobutane/Butane (20:78:2) Propellant A-46 Aeropres Propane/Isobutane/Butane (55:18:27) Propellant AP-70 Aeropres Tetrafluoroethane Propellant Dymel 134a DuPont
[0266] By way of non-limiting example, tests are briefly set out below as would be appreciated by a person of the art.
[0267] Collapse Time, which is a measure or indication of thermal stability, is examined by dispensing a given quantity of foam and photographing sequentially its appearance with time during incubation at 36 C. The collapse time result is defined as the time when the foam height reaches 50% of its initial height or if the foam has not yet reached 50% of its initial height after say 180 seconds then the collapse time is recorded as being >180 seconds. By way of illustration one foam may remain at 100% of its initial height for three minutes, a second foam may reach 90% of its initial height after three minutes, a third foam may reach 70% of its initial height after three minutes, and a fourth foam may reach 51 % of its initial height after three minutes, nevertheless in each of these four cases the collapse time is recorded as >l80secs since for practical purposes for easy application by a patient to a target the majority of the foam remains intact for more than 180secs. If the foam for example reaches 50% of its original height after say 100 seconds it would be recorded as having a collapse time of 100 seconds. It is useful for evaluating foam products, which maintain structural stability at skin temperature for at least 1 minute. Foams which are structurally stable on the skin for at least one minute are termed "short term stable" carriers or foams. A rough corollary of collapse time is drainage. If the collapse time is short the drainage is high. Each bubble is comprised of a liquid phase surrounding an air or gas phase. The liquid drains under the influence of gravitation force. When a bubble thins it ultimately collapses or joins with anther bubble. So foams with high drainage are inherently unstable. A further factor is expansion time. Some foams expand very rapidly whilst others expand quite slowly. Expansion time is a measure of how long a foam may take to reach its full expansion or lowest density. In some cases expansion and collapse can offset one another to some degree. So in one aspect, for example, whilst a foam is still expanding it has also begun to collapse. In another aspect, a thermolabile formulation that can collapse quite quickly in seconds upon expose to body temperature of about 36 C may nevertheless have quite a relatively long expansion time at 20 C. In certain aspects the collapse time, expansion time and drainage time can all be long.
[0268] Density: in this procedure, the foam product is dispensed into vessels (including dishes or tubes) of a known volume and weight. Replicate measurements of the mass of foam filling the vessels are made and the density is calculated. The canister and contents are allowed to reach room temperature. Shake the canister to mix the contents and dispense and discard 5-10 mL. Then dispense foam into a pre-weighed tube, filling it until excess is extruded. Immediately remove (level off) excess foam at both ends and weigh the filled tube on the weighing balance.
[0269] Viscosity is measured with Brookfield LVDV-II + PRO with spindle SC4-25 at ambient temperature and 20, 10, 5 and or 1 RPM. Viscosity is usually measured at 10RPM or 20RPM. However, at about the apparent upper limit for the spindle of ->50,000CP, the viscosity at 1RPM may be measured, although the figures are of a higher magnitude.
[0270] Shakability represents the degree to which the user is able to feel /
hear the presence of the liquid contents when the filled pressurized canister is shaken. Shaking is with normal mild force without vigorous shaking or excessive force. When the user cannot sense the motion of the contents during shaking the product may be considered to be non-shakable. This property may be of particular importance in cases where shaking is required for affecting proper dispersion of the contents.
Table of Shakability scoring Good shakability (conforms to required quality specification) 2 Moderate shakability (conforms to required quality specification) 1 Not shakable (fails to meet required quality specification) but may still be 0 flowable and allow foam formation of quality Is substantially not able to pass through valve Block
hear the presence of the liquid contents when the filled pressurized canister is shaken. Shaking is with normal mild force without vigorous shaking or excessive force. When the user cannot sense the motion of the contents during shaking the product may be considered to be non-shakable. This property may be of particular importance in cases where shaking is required for affecting proper dispersion of the contents.
Table of Shakability scoring Good shakability (conforms to required quality specification) 2 Moderate shakability (conforms to required quality specification) 1 Not shakable (fails to meet required quality specification) but may still be 0 flowable and allow foam formation of quality Is substantially not able to pass through valve Block
[0271] Bubble Size: Foams are made of gas bubbles entrapped in liquid. The bubble size and distribution reflects in the visual texture and smoothness of the foam. Foam bubbles size is determined by dispensing a foam sample on a glass slide, taking a picture of the foam surface with a digital camera equipped with a macro lens. The diameter of about 30 bubbles is measured manually relatively to calibration standard template. Statistical parameters such as mean bubble diameter, standard deviation and quartiles are then determined. Measuring diameter may also be undertaken with image analysis software. The camera is a Nikon D40X Camera (resolution l OMP) equipped with Sigma Macro Lens (ref: APO MACRO 150mm F2.8 EX DG HSM).
Pictures obtained are cropped to keep a squared region of 400 pixels x 400 pixels.
Pictures obtained are cropped to keep a squared region of 400 pixels x 400 pixels.
[0272] Chemical Stability: the amount of active agent present is analyzed chromatographically. Analysis is carried out after formulation preparation and at appropriate time intervals thereafter. The samples are typically stored in controlled temperature incubators at one or more of 5 C, 25 C and 40 C for several weeks or months. At appropriate time intervals samples are removed from the incubators and the concentration of active agent and or breakdown product is measured.
Example 2 - Formulations containing waxes and propellant or oil and propellant
Example 2 - Formulations containing waxes and propellant or oil and propellant
[0273] The foaming properties of formulations containing waxes and propellant with no additional solvent were studied. Formulations were prepared containing Paraffin wax 51-53 and different concentrations of propellant. Also a formulation with mineral oil and propellant was prepared. As shown in Tables 2a and 2b below, upon addition of propellant, the formulations did not produce foam. It can be appreciated that the formulation of quality waterless foams based on waxes is challenging without the presence of foam stabilizers such as surfactants either alone or combined with foam adjuvants.
Table 2a - Formulations containing waxes and propellant Formulations 001 002 003 Ingredients %w/w %w/w %w/w Paraffin wax 51-53 100.0 100.0 100.0 Total 100.0 100.0 100.0 Propellant AP-70 30.0 50.0 60.0 Results Foam Quality No Foam No Foam No Foam Table 2b - Formulation containing oil and propellant Formulations XX2b Ingredients %w/w Light mineral oil 100.0 Total 100.0 Propellant AP-70 10.0 Results Foam Quality Poor Comment: Neither mineral nor paraffin waxes alone were able to generate a foam.
Example 3 - Mineral oil-based formulations containing waxes
Table 2a - Formulations containing waxes and propellant Formulations 001 002 003 Ingredients %w/w %w/w %w/w Paraffin wax 51-53 100.0 100.0 100.0 Total 100.0 100.0 100.0 Propellant AP-70 30.0 50.0 60.0 Results Foam Quality No Foam No Foam No Foam Table 2b - Formulation containing oil and propellant Formulations XX2b Ingredients %w/w Light mineral oil 100.0 Total 100.0 Propellant AP-70 10.0 Results Foam Quality Poor Comment: Neither mineral nor paraffin waxes alone were able to generate a foam.
Example 3 - Mineral oil-based formulations containing waxes
[0274] The foaming properties of mixtures of oils and waxes were studied.
Formulations were prepared containing oils such as mineral oils and silicones in combination with waxes such as Paraffin wax 42-44, beeswax and hydrogenated castor oil were prepared, where the concentration of wax was from 10% to 20%. As shown in Table 3 below, upon addition of propellant, formulations 1-4 produced no more than bubbly liquids and formulations 8-10, although they were better, still only produced unstable fairly good quality foams that collapsed within seconds. It can be appreciated that the formulation of stable quality foams based on a combination of oils and waxes is challenging without the presence of foam stabilizers such as surfactants either alone or combined with foam adjuvants. Of all the formulations, parafin wax and mineral oil achieved the poorest result. Without being bound by any theory the variations between paraffin waxes and their success in generating foams may be due to one or more factors such as chain length, van der Waals forces, and CST as explained above in the discussion.
Table 3 - Mineral oil-based formulations containing waxes Formulations 004 005 006 007 008 009 010 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 80.0 60.0 80.0 60.0 60.0 85.0 85.0 Light Mineral oil - 30.0 - 25.0 25.0 - -Cyclomethicone - - - 5.00 5.00 - -Paraffin wax 42-44 20.0 - - - - - -Beeswax - 10.0 20.0 5.0 - - -Hydrogenated castor oil - - - 5.0 10.0 15.0 15.0 Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 - 8.0 - - 8.0 12.0 Propellant A-46 - 12.0 - 12.0 12.0 - -Results Foam Quality Poor Fair Fair Fair Fairly Fairly Fairly Good Good Good Collapse Time at 36 C (sec) - - - - 10 - -Example 4 - Mineral oil-based foam formulations containing 51-53 or 42-44 paraffin waxes
Formulations were prepared containing oils such as mineral oils and silicones in combination with waxes such as Paraffin wax 42-44, beeswax and hydrogenated castor oil were prepared, where the concentration of wax was from 10% to 20%. As shown in Table 3 below, upon addition of propellant, formulations 1-4 produced no more than bubbly liquids and formulations 8-10, although they were better, still only produced unstable fairly good quality foams that collapsed within seconds. It can be appreciated that the formulation of stable quality foams based on a combination of oils and waxes is challenging without the presence of foam stabilizers such as surfactants either alone or combined with foam adjuvants. Of all the formulations, parafin wax and mineral oil achieved the poorest result. Without being bound by any theory the variations between paraffin waxes and their success in generating foams may be due to one or more factors such as chain length, van der Waals forces, and CST as explained above in the discussion.
Table 3 - Mineral oil-based formulations containing waxes Formulations 004 005 006 007 008 009 010 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 80.0 60.0 80.0 60.0 60.0 85.0 85.0 Light Mineral oil - 30.0 - 25.0 25.0 - -Cyclomethicone - - - 5.00 5.00 - -Paraffin wax 42-44 20.0 - - - - - -Beeswax - 10.0 20.0 5.0 - - -Hydrogenated castor oil - - - 5.0 10.0 15.0 15.0 Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 - 8.0 - - 8.0 12.0 Propellant A-46 - 12.0 - 12.0 12.0 - -Results Foam Quality Poor Fair Fair Fair Fairly Fairly Fairly Good Good Good Collapse Time at 36 C (sec) - - - - 10 - -Example 4 - Mineral oil-based foam formulations containing 51-53 or 42-44 paraffin waxes
[0275] The foaming properties of formulations containing mineral oil and a paraffin wax having a melting point of about 51-53 C were studied. As shown in Table 4a, 4b and 4c below, formulations containing 5% pararafin wax 51-53 C (and by extrapolation less than 5%) only produced bubbly liquids. 7.5% paraffin wax 51-53 C only produced fairly good foam.
Formulations containing 55% and 60% pararafin wax 51-53 C (and by extrapolation more than 60%) did not produce foam and a semi-solid content was expelled even upon increasing the concentration of propellant to 12% and to 16%. However, formulations contaning from 10% to 50% paraffin wax 51-53, succesfully generated good to excellent quality foams having a collapse time of about 2 minutes or higher at 36 C. These results are surprising given the fact that no known foam stabilizing agent such as surfactants is present and that the phenomena is concentration dependent. Moreover, no foam adjuvant such as a fatty alcohol or fatty acid is needed, and formulations containing only waxes generated quality foams. For high amounts of waxes, the inclusion of higher amounts of propellant was found useful, for example, in order to improve the flowability of the formulation within the canister, as can be shown in by the shakability results. For example, a formulation containing 50% heavy mineral oil and 50%
paraffin wax 51-53 was pressurized with 8% propellant or 12% propellant (See Table 4c). With 8% propellant, the composition was such that a block occurred with substantailly no content being expelled through the canister valve. However, increasing the amount of propellant to 12%
enabled quality foam to be expelled. Additionally, as can be seen from formulations 31-34 that increasing propellant from 8% to 12% also resulted in a similar increase in collapse time from about 80secs to about 120secs. Without being bound by any theory it may be that the propellant was successful in reducing the viscosity of the formulation and or wax in the valve. The physical properties of formulation 016 containing 20% paraffin wax 51-53 are presented in Table 4e.
Formulations containing 55% and 60% pararafin wax 51-53 C (and by extrapolation more than 60%) did not produce foam and a semi-solid content was expelled even upon increasing the concentration of propellant to 12% and to 16%. However, formulations contaning from 10% to 50% paraffin wax 51-53, succesfully generated good to excellent quality foams having a collapse time of about 2 minutes or higher at 36 C. These results are surprising given the fact that no known foam stabilizing agent such as surfactants is present and that the phenomena is concentration dependent. Moreover, no foam adjuvant such as a fatty alcohol or fatty acid is needed, and formulations containing only waxes generated quality foams. For high amounts of waxes, the inclusion of higher amounts of propellant was found useful, for example, in order to improve the flowability of the formulation within the canister, as can be shown in by the shakability results. For example, a formulation containing 50% heavy mineral oil and 50%
paraffin wax 51-53 was pressurized with 8% propellant or 12% propellant (See Table 4c). With 8% propellant, the composition was such that a block occurred with substantailly no content being expelled through the canister valve. However, increasing the amount of propellant to 12%
enabled quality foam to be expelled. Additionally, as can be seen from formulations 31-34 that increasing propellant from 8% to 12% also resulted in a similar increase in collapse time from about 80secs to about 120secs. Without being bound by any theory it may be that the propellant was successful in reducing the viscosity of the formulation and or wax in the valve. The physical properties of formulation 016 containing 20% paraffin wax 51-53 are presented in Table 4e.
[0276] Formulations were prepared, based on the combination of mineral oil with a paraffin wax having a melting point of about 42-44 C. Both in the case of light and heavy mineral oil, breakable foams of quality were obtained having a collapse time of more than 1 minute at 36 C
when 40% of paraffin wax 42-44 was used. Notably, the stability of the foams at 36 C was improved by using higher amounts of propellant.
when 40% of paraffin wax 42-44 was used. Notably, the stability of the foams at 36 C was improved by using higher amounts of propellant.
[0277] Formulations were prepared, based on the combination of mineral oil with a paraffin wax having a melting point of about 58-62 C. Breakable foams of quality having a density between 0.1 and 0.2 g/mL and a collapse time of more than 3 minute at 36 C
were obtained when 10% and 20% of paraffin wax 58-62 were used.
were obtained when 10% and 20% of paraffin wax 58-62 were used.
[0278] Table 4e indicates that the formulation can exist as three separate phases when left to stand, viz, oil, wax, and propellant but re-disperses on moderate shaking.
[0279] In one or more embodiments, there is provided a foamable formulation containing a mineral oil, a paraffin wax and a propellant, wherein the formulation provides upon dispensing a breakable foam of quality which exhibits a collapse time when placed on a surface at 36 C (or between about 20 C to 36 C) of about or more than 1 minute. In one or more embodiments the collapse time is about or more than 11/2 minutes; is about or more than 2 minutes; is about or more than 21/2 minutes; or is about or more than 3 minutes.
Table 4a - Mineral oil-based foam formulations containing paraffin waxes Formulations 011 012 013 014 015 016 017 018 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 95.0 92.5 90.0 87.5 85.0 80.0 75.0 72.5 Paraffin wax 51-53 5.0 7.5 10.0 12.5 15.0 20.0 25.0 27.5 Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 8.0 8.0 8.0 8.0 8.0 8.0 8.0 Results Foam Quality Poor Fairly Good- Good Excellent Excellent Excellent Excellent Good Shakability 2 2 2 2 2 2 1 1 Collapse Time at 36 C (sec) - - 110 135 >180 >180 >180 >180 Table 4b - Mineral oil-based foam formulations containing paraffin waxes (cont.) Formulations 019 020 021 022 023 024 025 026 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 70 67.5 65.0 65.0 60.0 60.0 55.0 55.0 Paraffin wax 51-53 30 32.5 35.0 35.0 40.0 40.0 45.0 45.0 Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 8.0 8.0 12.0 8.0 12.0 8.0 12.0 Results Foam Quality Excellent Excellent Excellent Excellent Excellent Excellent Block Excellent Shakability 1 1 1 2 0 1 - 0 Collapse Time at 36 C (sec) >180 >180 >180 >180 >180 >180 - >180 Table 4c - Mineral oil-based foam formulations containing paraffin waxes (cont.) Formulations 027 028 XX4ca XX4cb 029 030 031 032 033 034 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 50.0 50.0 35.0 30.0 - - 60.0 60.0 - -Light Mineral oil - - - - 60.0 60.0 - - 60.0 60.0 Paraffin wax 42-44 - - - - - - 40.0 40.0 40.0 40.0 Paraffin wax 51-53 50.0 50.0 55.0 60.0 40.0 40.0 - - - -Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 12.0 8 or 12 16.0 8.0 12.0 8.0 12.0 8.0 12.0 or 16.0 Results No foam No foam (semi- (semi-Foam Quality Block Excellent solid solid Excellent Excellent Excellent Excellent Excellent Excellent content content expelled) expelled) Shakability - 0 1 1 1 2 1 2 1 2 Collapse Time at - >180 - - >180 >180 85 120 80 125 36 C (sec) Table 4d - Mineral oil-based foam formulations containing paraffin waxes (cont.) Formulations 035 036 037 038 Ingredients %w/w %w/w %w/w %w/w Heavy mineral oil 90.0 80.0 80.0 70.0 C12-C15 Alkyl benzoate - - - 10.0 Paraffin wax 58-62 10.0 20.0 20.0 20.0 Total Propellant AP-70 8.0 8.0 12.0 12.0 Results Foam Quality Excellent Excellent Excellent Excellent Foam Density (g/ml) 0.135 0.119 0.129 0.177 Shakability 1 1 2 2 Collapse Time at 36 C (sec) >180 >180 >180 >180 Table 4e - Physical properties of formulation 016 Formulations 016 Ingredients %w/w Heavy mineral oil 80.0 Paraffin wax 51-53 20.0 Total Propellant AP-70 8.0 Results Foam Quality E
Shakability 2 Density (g/ml) 0.230 Collapse Time at 36 C (see) >180 Expansion time (see) 240 Hardness (g) 9 Total dispensed weight (%) 82.40 Mean Bubble size (nm) 259 Inspection in Pressurized Glass bottle 3 phases PFF Centrifugation 3K rpm for 10 min 3 phases PFF Centrifugation IOK rpm for 10 min 3 phases PFF Viscosity at 10rpm (eP) 4303
Table 4a - Mineral oil-based foam formulations containing paraffin waxes Formulations 011 012 013 014 015 016 017 018 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 95.0 92.5 90.0 87.5 85.0 80.0 75.0 72.5 Paraffin wax 51-53 5.0 7.5 10.0 12.5 15.0 20.0 25.0 27.5 Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 8.0 8.0 8.0 8.0 8.0 8.0 8.0 Results Foam Quality Poor Fairly Good- Good Excellent Excellent Excellent Excellent Good Shakability 2 2 2 2 2 2 1 1 Collapse Time at 36 C (sec) - - 110 135 >180 >180 >180 >180 Table 4b - Mineral oil-based foam formulations containing paraffin waxes (cont.) Formulations 019 020 021 022 023 024 025 026 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 70 67.5 65.0 65.0 60.0 60.0 55.0 55.0 Paraffin wax 51-53 30 32.5 35.0 35.0 40.0 40.0 45.0 45.0 Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 8.0 8.0 12.0 8.0 12.0 8.0 12.0 Results Foam Quality Excellent Excellent Excellent Excellent Excellent Excellent Block Excellent Shakability 1 1 1 2 0 1 - 0 Collapse Time at 36 C (sec) >180 >180 >180 >180 >180 >180 - >180 Table 4c - Mineral oil-based foam formulations containing paraffin waxes (cont.) Formulations 027 028 XX4ca XX4cb 029 030 031 032 033 034 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 50.0 50.0 35.0 30.0 - - 60.0 60.0 - -Light Mineral oil - - - - 60.0 60.0 - - 60.0 60.0 Paraffin wax 42-44 - - - - - - 40.0 40.0 40.0 40.0 Paraffin wax 51-53 50.0 50.0 55.0 60.0 40.0 40.0 - - - -Total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 12.0 8 or 12 16.0 8.0 12.0 8.0 12.0 8.0 12.0 or 16.0 Results No foam No foam (semi- (semi-Foam Quality Block Excellent solid solid Excellent Excellent Excellent Excellent Excellent Excellent content content expelled) expelled) Shakability - 0 1 1 1 2 1 2 1 2 Collapse Time at - >180 - - >180 >180 85 120 80 125 36 C (sec) Table 4d - Mineral oil-based foam formulations containing paraffin waxes (cont.) Formulations 035 036 037 038 Ingredients %w/w %w/w %w/w %w/w Heavy mineral oil 90.0 80.0 80.0 70.0 C12-C15 Alkyl benzoate - - - 10.0 Paraffin wax 58-62 10.0 20.0 20.0 20.0 Total Propellant AP-70 8.0 8.0 12.0 12.0 Results Foam Quality Excellent Excellent Excellent Excellent Foam Density (g/ml) 0.135 0.119 0.129 0.177 Shakability 1 1 2 2 Collapse Time at 36 C (sec) >180 >180 >180 >180 Table 4e - Physical properties of formulation 016 Formulations 016 Ingredients %w/w Heavy mineral oil 80.0 Paraffin wax 51-53 20.0 Total Propellant AP-70 8.0 Results Foam Quality E
Shakability 2 Density (g/ml) 0.230 Collapse Time at 36 C (see) >180 Expansion time (see) 240 Hardness (g) 9 Total dispensed weight (%) 82.40 Mean Bubble size (nm) 259 Inspection in Pressurized Glass bottle 3 phases PFF Centrifugation 3K rpm for 10 min 3 phases PFF Centrifugation IOK rpm for 10 min 3 phases PFF Viscosity at 10rpm (eP) 4303
[0280] The following example illustrates the physical stability of oleaginous foam formulation 016. In an accelerated stability study, samples were stored at 40 C, and parameters indicating physical stability such as foam quality, shakability, foam density and foam collapse time were determined. The stability test results following 1 and 2 months of storage at 40 C are shown in Table 4f.
Table 4f - Physical properties of formulation 016 after 1 and 2 months at 40 C
Tests TO 1 month at 40 C 2 months at 40 C
Foam Quality E E E
Shakability Good Poor - after vigorous Poor - after vigorous shaking became good shaking moderate Foam Density (g/ml) 0.225 0.221 0.235 Collapse Time at 36 C (see) >180 >180 >180
Table 4f - Physical properties of formulation 016 after 1 and 2 months at 40 C
Tests TO 1 month at 40 C 2 months at 40 C
Foam Quality E E E
Shakability Good Poor - after vigorous Poor - after vigorous shaking became good shaking moderate Foam Density (g/ml) 0.225 0.221 0.235 Collapse Time at 36 C (see) >180 >180 >180
[0281] Formulation 016 is physically stable after 2 months of storage at 40 C.
The decrease in formulation shakability may be explained by a partial solidification of the wax content with time. It may be overcome inter alia by increasing the propellant concentration of the formulation to about 12%, or by using a propellant having a higher vapor pressure such as propane. So for example a smaller amount of higher pressure propellant may be used instead of a higher amount of a lower pressure propellant. In one or more embodiments the amount of propellant is at least about 11%; is at least about 12%; is at least about 13%; is at least about 14%; is at least about 15%; is at least about 16%; is at least about 17%; or is at least about 18%.
In one or more embodiments the vapor pressure of the propellant is at least about 10 psi; is at least about 30 psi ;
is at least about 50 psi ; is at least about 70 psi ; is at least about 90 psi ; is at least about 110 psi ; is at least about 130 psi ; or is at least about 150 psi. In one or more embodiments the vapor pressure of the propellant is between about 25 psi to about 125 psi. In one or more embodiments the vapor pressure of the propellant is between about 10 psi to about 130 psi. In one or more embodiments the vapor pressure of the propellant is between about 10 psi to about 30 psi;
between about 25 psi to about 50 psi; between about 50 psi to about 70 psi; between about 70 psi to about 30 psi;
between about 70 psi to about 90 psi; between about 90 psi to about 130 psi;
between about 110 psi to about 130 psi; between about 30 psi to about 110 psi; between about 40 psi to about 90 psi.
Example 5 -Foam formulations containing waxes and various oils
The decrease in formulation shakability may be explained by a partial solidification of the wax content with time. It may be overcome inter alia by increasing the propellant concentration of the formulation to about 12%, or by using a propellant having a higher vapor pressure such as propane. So for example a smaller amount of higher pressure propellant may be used instead of a higher amount of a lower pressure propellant. In one or more embodiments the amount of propellant is at least about 11%; is at least about 12%; is at least about 13%; is at least about 14%; is at least about 15%; is at least about 16%; is at least about 17%; or is at least about 18%.
In one or more embodiments the vapor pressure of the propellant is at least about 10 psi; is at least about 30 psi ;
is at least about 50 psi ; is at least about 70 psi ; is at least about 90 psi ; is at least about 110 psi ; is at least about 130 psi ; or is at least about 150 psi. In one or more embodiments the vapor pressure of the propellant is between about 25 psi to about 125 psi. In one or more embodiments the vapor pressure of the propellant is between about 10 psi to about 130 psi. In one or more embodiments the vapor pressure of the propellant is between about 10 psi to about 30 psi;
between about 25 psi to about 50 psi; between about 50 psi to about 70 psi; between about 70 psi to about 30 psi;
between about 70 psi to about 90 psi; between about 90 psi to about 130 psi;
between about 110 psi to about 130 psi; between about 30 psi to about 110 psi; between about 40 psi to about 90 psi.
Example 5 -Foam formulations containing waxes and various oils
[0282] The foaming properties of formulations containing various hydrophobic solvents and a paraffin wax having a melting point of about 51-53 C were studied. As shown in Table 5 below, formulations containing oil such as capric/caprylic triglycerides, PPG-15 Stearyl ether, isopropyl palmitate, isopropyl myristate or octyldodecanol combined with 20%
paraffin wax 51-53 produced breakable foams of quality having a collapse time of more than 1 minute at 36 C.
paraffin wax 51-53 produced breakable foams of quality having a collapse time of more than 1 minute at 36 C.
[0283] In one or more embodiments, there is provided a foamable formulation containing a hydrophobic solvent, a paraffin wax and a propellant, wherein the formulation provides upon dispensing a breakable foam of quality which exhibits a collapse time when placed on a surface at 36 C (or between about 20 C to 36 C) of about or more than 1 minute. In one or more embodiments the collapse time is about or more than 11/2 minutes; is about or more than 2 minutes; is about or more than 21/2 minutes; is about or more than 3 minutes Table 5 - Foam formulations containing waxes and various oils Formulations 039 040 041 042 043 Ingredients %w/w %w/w %w/w %w/w %w/w Capric/caprylic triglycerides 80.0 - - - -PPG-15 Stearyl ether - 80.0 - - -Isopropyl palmitate - - 80.0 - -Isopropyl myristate - - - 80.0 -Octyldodecanol - - - - 80.0 Paraffin wax 51-53 20.0 20.0 20.0 20.0 20.0 Total 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 8.0 8.0 8.0 8.0 Results Foam Quality Excellent Excellent Good Good Good Shakability 2 2 2 2 2 Collapse Time at 36 C (sec) >180 >180 180 >180 165 Example 6 - Foam formulations containing oils, waxes and various propellants
[0284] The foaming properties of formulations containing mineral oil, a paraffin wax and various types of propellants were studied. As shown in Table 6 below, formulations containing hydrocarbon propellants such as AP-70 and A-46, and hydrofluorocarbon propellants such as Dymel 134a produced breakable foams of quality having a collapse time of more than 1 minute at 36 C.
Table 6 - Foam formulations containing oils, waxes and various propellants Formulations 044 045 046 Ingredients %w/w %w/w %w/w Heavy mineral oil 80.0 80.0 80.0 Paraffin wax 51-53 20.0 20.0 20.0 Total 100.0 100.0 100.0 Propellant AP-70 (vapor pressure = 70 8.0 psi) Propellant A-46(vapor pressure = 46 - 8.0 -psi) Propellant Dymel 134a (vapor pressure - - 15.0 =96.6 psi) Results Foam Quality Excellent Good Excellent Shakability 2 2 2 Collapse Time at 36 C (sec) >180 >180 >180 Example 7 - Foam formulations containing oils, and various waxes
Table 6 - Foam formulations containing oils, waxes and various propellants Formulations 044 045 046 Ingredients %w/w %w/w %w/w Heavy mineral oil 80.0 80.0 80.0 Paraffin wax 51-53 20.0 20.0 20.0 Total 100.0 100.0 100.0 Propellant AP-70 (vapor pressure = 70 8.0 psi) Propellant A-46(vapor pressure = 46 - 8.0 -psi) Propellant Dymel 134a (vapor pressure - - 15.0 =96.6 psi) Results Foam Quality Excellent Good Excellent Shakability 2 2 2 Collapse Time at 36 C (sec) >180 >180 >180 Example 7 - Foam formulations containing oils, and various waxes
[0285] The foaming properties of formulations containing mineral oil, a propellant and other types of waxes were studied. As shown in Table 7 below, formulations containing solid waxes, namely about 20% hydrogenated castor oil, and formulations containing about 30% or about 40%
beeswax produced breakable foams of quality having a collapse time of more than 1 minute at 36 C. For high amounts of waxes, the inclusion of higher amounts of propellant was found useful in order to improve the flowability of the formulation within the canister, as can be shown in by the shakability results.
beeswax produced breakable foams of quality having a collapse time of more than 1 minute at 36 C. For high amounts of waxes, the inclusion of higher amounts of propellant was found useful in order to improve the flowability of the formulation within the canister, as can be shown in by the shakability results.
[0286] In one or more embodiments, there is provided a foamable formulation containing a hydrophobic solvent, a wax and a propellant, wherein the formulation provides upon dispensing a breakable foam of quality which does not collapse at 36 C for more than 1 minute.
Table 7 - Foam formulations containing oils, waxes and other waxes Formulations 047 048 049 050 051 052 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 80.0 80.0 60.0 60.0 70.0 70.0 Beeswax - - 40.0 40.0 30.0 30.0 Hydrogenated castor oil 20.0 20.0 - - - -Total 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 12.0 8.0 12.0 8.0 12.0 Results Foam Quality Good Good Good Excellent Good Good Shakability 0 0 0 1 1 2 Collapse Time at 36 C (sec) - >180 - >180 >180 >180 Example 8 - Foam formulations containing oils, waxes and various active ingredients
Table 7 - Foam formulations containing oils, waxes and other waxes Formulations 047 048 049 050 051 052 Ingredients %w/w %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 80.0 80.0 60.0 60.0 70.0 70.0 Beeswax - - 40.0 40.0 30.0 30.0 Hydrogenated castor oil 20.0 20.0 - - - -Total 100.0 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 12.0 8.0 12.0 8.0 12.0 Results Foam Quality Good Good Good Excellent Good Good Shakability 0 0 0 1 1 2 Collapse Time at 36 C (sec) - >180 - >180 >180 >180 Example 8 - Foam formulations containing oils, waxes and various active ingredients
[0287] The foaming properties of formulations containing mineral oil, a paraffin wax, a propellant and various active ingredients were studied. As shown in Table 8 below, formulations containing minocycline HC1, benzoyl peroxide (BPO), mometasone fuorate, calcitriol and lidocaine produced breakable foams of quality having a collapse time of more than 1 minute at 36 C. However, BPO and paraffin wax formed a block on repeated use.
Table 8 - Foam formulations containing oils, waxes and various active ingredients Formulations 053 054 055 056 057 Ingredients %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 79.0 75.0 79.9 79.9985 75.0 Paraffin 51-53 20.0 20.0 20.0 20.0 20.0 Minocycline HCL 1.0 - - - -Benzoyl peroxide - 5.0 - - -Mometasone furoate - - 0.10 - -Calcitriol - - - 0.0015 -Lidocaine - - - - 5.0 Total 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 12.0 8.0 12.0 8.0 Results Foam Quality Excellent Excellent Excellent Excellent Excellent Shakability 2 2 2 2 2 Collapse Time at 36 C (sec) >180 Block >180 >180 >180 Example 9 - Compatibility Study
Table 8 - Foam formulations containing oils, waxes and various active ingredients Formulations 053 054 055 056 057 Ingredients %w/w %w/w %w/w %w/w %w/w Heavy mineral oil 79.0 75.0 79.9 79.9985 75.0 Paraffin 51-53 20.0 20.0 20.0 20.0 20.0 Minocycline HCL 1.0 - - - -Benzoyl peroxide - 5.0 - - -Mometasone furoate - - 0.10 - -Calcitriol - - - 0.0015 -Lidocaine - - - - 5.0 Total 100.0 100.0 100.0 100.0 100.0 Propellant AP-70 8.0 12.0 8.0 12.0 8.0 Results Foam Quality Excellent Excellent Excellent Excellent Excellent Shakability 2 2 2 2 2 Collapse Time at 36 C (sec) >180 Block >180 >180 >180 Example 9 - Compatibility Study
[0288] Procedure: Minocycline hydrochloride ("MCH") was incubated as a suspension with various excipients at 25 C and 40 C for maximum of sixty days or to the point where degradation was suspected. The ratio between MCH and the tested excipient is detailed below. Visual inspection was the major criterion for indication of compatibility. The color of intact MCH
suspension is pale yellow; and any change of color (e.g., to dark orange, red, green, brown and black) indicates oxidation or degradation.
suspension is pale yellow; and any change of color (e.g., to dark orange, red, green, brown and black) indicates oxidation or degradation.
[0289] Hydrophilic solvents were tested for compatibility with MCH at a ratio of MCH:
excipient of 1:250. Dimethyl Isosorbide, Glycerin, Ethanol, Propylene glycol, Butylene Glycol, PEG 200, Hexylene Glycol, PEG 400, Dimethyl Sulfoxide and Diethylene glycol monoethyl ether were found to be incompatible with MCH.
excipient of 1:250. Dimethyl Isosorbide, Glycerin, Ethanol, Propylene glycol, Butylene Glycol, PEG 200, Hexylene Glycol, PEG 400, Dimethyl Sulfoxide and Diethylene glycol monoethyl ether were found to be incompatible with MCH.
[0290] Oily emollients and waxes were tested for compatibility with MCH at a ratio of MCH:
excipient of 1:250 for Oily emollients and 1:50 for waxes. Hydrogenated castor oil, Castor oil, Cocoglycerides, Disopropyl adipate, Mineral oil light, Coconut oil, Beeswax, MCT oil, Cyclomethicone, Isododecane, Cetearyl octanoate, Gelled mineral oil, Isopropyl myristate, PPG
15 stearyl ether, Mineral oil heavy, Octyl dodecanol, White Petrolatum, Petrolatum (Sofmetic), Paraffin 51-53, Calendula oil, Shea butter, Grape seed oil, Almond oil, Jojoba oil, Avocado oil, Peanut oil, Wheat germ oil and Hard Fat were found to be compatible with MCH.
Pomegranate seed oil was found to be incompatible with MCH.
excipient of 1:250 for Oily emollients and 1:50 for waxes. Hydrogenated castor oil, Castor oil, Cocoglycerides, Disopropyl adipate, Mineral oil light, Coconut oil, Beeswax, MCT oil, Cyclomethicone, Isododecane, Cetearyl octanoate, Gelled mineral oil, Isopropyl myristate, PPG
15 stearyl ether, Mineral oil heavy, Octyl dodecanol, White Petrolatum, Petrolatum (Sofmetic), Paraffin 51-53, Calendula oil, Shea butter, Grape seed oil, Almond oil, Jojoba oil, Avocado oil, Peanut oil, Wheat germ oil and Hard Fat were found to be compatible with MCH.
Pomegranate seed oil was found to be incompatible with MCH.
[0291] The compatibility of MCH with hydrophobic surfactant was tested following solubilization of the surfactant in mineral oil (mineral oil was previously shown to be compatible with MCH). Surfactants were tested for compatibility with MCH at a ratio of MCH: excipient of 1:50. PEG150 distearate, Laureth 4, PEG 40 hydrogenated castor oil, PEG 75 lanolin, Glucam P20 distearate, PEG 100 stearate, Glyceryl monostearate, PEG 40 stearate, Montanov S (Cocoyl Alcohol (and) C12-20 Alkyl Glucoside)), Alkyl lactate, Benton gel, SPAN 60, Sorbitan sesquistearate, SPAN 40, Tween 20, Ceteth 2, Sucrose stearic acid esters D1813, Ceteareth 20, Steareth 2/Steareth 21, Methyl glucose sesquistearate, Oleth 20, PPG 20 methyl glucose ether, Tween 60 were found to be incompatible with MCH. Sucrose stearic acid esters D1803, Sucrose stearic acid esters D1807 and Sucrose stearic acid esters D1811 were found to be compatible with MCH; however, not all of them dissolved in oil (e.g. 1811, 1813).
[0292] Foam adjuvants were tested for compatibility with MCH at a ratio of MCH: excipient of 1:50. Isostearyl alcohol, Behenyl alcohol, Stearyl alcohol, Cetyl alcohol, Oleyl alcohol, Myristyl alcohol, Cetostearyl alcohol, Palmitic acid, Stearic acid and Oleic acid were found to be compatible with MCH. Isostearic acid was not compatible with MCH.
[0293] Additives were tested for compatibility with MCH at a ratio of MCH:
excipient of 1:50. Aerosil and Menthol were found to be compatible with MCH. Titanium dioxide and Ethocel were not compatible with MCH.
excipient of 1:50. Aerosil and Menthol were found to be compatible with MCH. Titanium dioxide and Ethocel were not compatible with MCH.
[0294] Additives were tested for compatibility with MCH. Minimal quantities of water (100 L) were added to MCH, suspended in excipients that had demonstrated compatibility to examine whether water can enhance oxidation/degradation in the absence or presence of antioxidant. In parallel, antioxidants were added to the MCH suspensions comprising water.
Antioxidants were also added to excipients which were found to be non compatible with MCH.
Addition of water caused prompt degradation of MCH. Addition of the antioxidants alpha-tocopherol, BHA/BHT and propyl gallate did not prevent MCH degradation.
Compatible excipients became incompatible in the presence of water. Addition of antioxidants did not alter this result.
Antioxidants were also added to excipients which were found to be non compatible with MCH.
Addition of water caused prompt degradation of MCH. Addition of the antioxidants alpha-tocopherol, BHA/BHT and propyl gallate did not prevent MCH degradation.
Compatible excipients became incompatible in the presence of water. Addition of antioxidants did not alter this result.
Claims (27)
1. A substantially surfactant free and substantially foam adjuvant free foamable composition comprising:
a) about 40% to about 92% by weight of a hydrophobic solvent;
b) about 8% to about 50% by weight of a wax comprising paraffin wax.
c) a liquefied or compressed gas propellant;
wherein the percent by weight is based on weight foamable composition; wherein the ratio of composition other than propellant to propellant is from about 100:1 to about 100:30; and wherein the total weight of the hydrophobic solvent and wax is together between about 95%
about 100% by weight and wherein upon dispensing the foamable carrier composition forms a breakable foam that is stable, yet breaks easily upon application of shear force.
a) about 40% to about 92% by weight of a hydrophobic solvent;
b) about 8% to about 50% by weight of a wax comprising paraffin wax.
c) a liquefied or compressed gas propellant;
wherein the percent by weight is based on weight foamable composition; wherein the ratio of composition other than propellant to propellant is from about 100:1 to about 100:30; and wherein the total weight of the hydrophobic solvent and wax is together between about 95%
about 100% by weight and wherein upon dispensing the foamable carrier composition forms a breakable foam that is stable, yet breaks easily upon application of shear force.
2. The composition of claim 1, further comprising at least one active agent.
3. The composition of claim 2, wherein the active agent is selected form the group consisting of an active herbal extract, an acaricides, an age spot and keratose removing agent, an allergen, an alpha hydroxyl acid, an analgesic agent, an antiacne agent, an antiallergic agent, an antiaging agent, an antibacterial agent, an antibiotic, an antibum agent, an anticancer agent, an antidandruff agent, an antidepressant, an antidermatitis agent, an antiedemic anent, an antifungal agent, an antihistamine, an antihelminth agent, an antihyperkeratolyte agent, an anti-infective agent, an antiinflammatory agent, an antiirritant, an antilipemic agent, an antimicrobial agent, an antimycotic agent, an antioxidant, an antiparasitic agent, an antiproliferative agent, an antipruritic agent, an antipsoriatic agent, an antirosacea agent, an antiseborrheic agent, an antiseptic agent, an antiswelling agent, an antiviral agent, an anti-wart agent, an anti-wrinkle agent, an antiyeast agents, an astringent, a beta-hydroxy acid, benzoyl peroxide, a topical cardiovascular agent, a chemotherapeutic agent, a corticosteroid, an immunogenic substance, a dicarboxylic acid, a disinfectant, a fungicide, a hair growth regulator, a haptene, a hormone, a hydroxy acid, an immunosuppressant, an immunoregulating agent, an immunomodulator, an insecticide, an insect repellent, a keratolytic agent, a lactam, a local anesthetic agent, a lubricating agent, a masking agent, a metals, a metal oxide, a mitocide, a neuropeptide, a non-steroidal anti-inflammatory agent, an oxidizing agent, a pediculicide, a peptide, a protein, a photodynamic therapy agent, a radical scavenger, a refatting agent, a retinoid, a sanative, a scabicide, a self tanning agent, a skin protective agent, a skin whitening agent, a steroid, a steroid hormone, a vasoconstrictor, a vasodilator, a vitamin, a vitamin A, a vitamin A
derivative, a vitamin B, a vitamin B derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D
derivative, a vitamin D analog, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K
derivative, a wound healing agent and a wart remover, an androgen, an anti-hyperkeratosis agent, an estrogen, an immunostimulant, a pesticide, a progesterone, a sedative, and a vaso active agent.
derivative, a vitamin B, a vitamin B derivative, a vitamin C, a vitamin C derivative, a vitamin D, a vitamin D
derivative, a vitamin D analog, a vitamin F, a vitamin F derivative, a vitamin K, a vitamin K
derivative, a wound healing agent and a wart remover, an androgen, an anti-hyperkeratosis agent, an estrogen, an immunostimulant, a pesticide, a progesterone, a sedative, and a vaso active agent.
4. The composition of claim 2, wherein the active agent is a tetracycline antibiotic.
5. The composition of claim 4, wherein the active agent is minocycline or doxycycline.
6. The composition of claim 1, wherein the composition is essentially waterless.
7. The composition of claim 1, wherein the composition is essentially foam adjuvant free.
8. The composition of claim 1, wherein the composition is surfactant free and foam adjuvant free.
9. The composition of claim 1, wherein the composition is surfactant free and foam adjuvant free and polymeric agent free.
10. The composition of claim 1, wherein the composition is essentially free of polyols.
11. The composition of claim 1, wherein the paraffin wax is selected from the group consisting of paraffin wax 58-62 °C, paraffin wax 51-53 °C, and paraffin wax 42-44 °C, or mixtures thereof.
12. The composition of claim 1, wherein the vapor pressure of the propellant is between about 10 psi and about 130 psi.
13. The composition of claim 1, wherein the composition is free of short chain alcohols.
14. The composition of claim 1, wherein the composition is a single phase.
15. The composition of claim 1, wherein the hydrophobic solvent is an oil.
16. The composition of claim 1, wherein the hydrophobic solvent is selected from the group consisting of hydrocarbon oils, mineral oil, liquid paraffin, isoparaffin, polyalphaolefin, polyolefin, polyisobutylene, synthetic isoalkane, isohexadecane isododecane, ester oils, alkyl benzoate, alkyl octanoate, C12-C15 alkyl benzoate, C12-Cl5 alkyl octanoate, arachidyl behenate, arachidyl propionate, benzyl laurate, benzyl myristate, benzyl palmitate, bis (octyldodecyl stearoyl) dimer dilinoleate, butyl myristate, butyl stearate, cetearyl ethylhexanoate, cetearyl isononanoate, cetyl acetate, cetyl ethylhexanoate, cetyl lactate, cetyl myristate, cetyl octanoate, cetyl palmitate, cetyl ricinoleate, decyl oleate, diethyleneglycol diethylhexanoate, diethyleneglycol dioctanoate, diethyleneglycol diisononanoate, diethyleneglycol diisononanoate, diethylhexanoate, diethylhexyl adipate, diethylhexyl malate, diethylhexyl succinate, diisopropyl adipate, diisopropyl dimerate, diisopropyl sebacate, diisosteary dimer dilinoleate, diisostearyl fumerate, dioctyl malate, dioctyl sebacate, dodecyl oleate, ethylhexyl palmitate, ester derivatives of lanolic acid, ethylhexyl cocoate, ethylhexyl ethylhexanoate, ethylhexyl hydroxystarate, ethylhexyl isononanoate, ethylhexyl palmytate, ethylhexyl pelargonate, ethylhexyl stearate, hexadecyl stearate, hexyl laurate, isoamyl laurate, isocetyl isocetyl behenate, isocetyl lanolate, isocetyl palmitate, isocetyl stearate, isocetyl salicylate, isocetyl stearate, isocetyl stearoyl stearate, isocetearyl octanoate, isodecyl ethylhexanoate, isodecyl isononanoate, isodecyl oleate, isononyl isononanoate, isodecyl oleate, isohexyl decanoate, isononyl octanoate, isopropyl isostearate, isopropyl lanolate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearyl behenate, isosteary citrate, isostearyl erucate, isostearyl glycolate, isostearyl isononanoate, isostearyl isostearate, isostearyl lactate, isostearyl linoleate, isostearyl linolenate, isostearyl malate, isostearyl neopentanoate, isostearyl palmitate, isosteary salicylate, isosteary tartarate, isotridecyl isononanoate, isotridecyl isononanoate, lauryl lactate, myristyl lactate, myristyl myristate, myristyl neopentanoate, myristyl propionate, octyldodecyl myristate, neopentylglycol dicaprate, octyl dodecanol, octyl stearate, octyl palmitate, octyldodecyl behenate, octyldodecyl hydroxystearate, octyldodecyl myristate, octyldodecyl stearoyl stearate, oleyl erucate, oleyl lactate, oleyl oleate, propyl myristate, propylene glycol myristyl ether acetate, propylene glycol dicaprate, propylene glycol dicaprylate, propylene glycol dicaprylate, maleated soybean oil, stearyl caprate, stearyl heptanoate, stearyl propionate, tocopheryl acetate, tocopheryl linoleate, glyceryl oleate, tridecyl ethylhexanoate, tridecyl isononanoate and triisocetyl citrate, triglycerides, oils of plant origin, alexandria laurel tree oil, avocado oil, apricot stone oil, barley oil, borage seed oil, calendula oil, canelle nut tree oil, canola oil, caprylic/capric triglyceride castor oil, coconut oil, corn oil, cotton oil, cottonseed oil, evening primrose oil, flaxseed oil, groundnut oil, hazelnut oil, glycereth triacetate, glycerol triheptanoate, glyceryl trioctanoate, glyceryl triundecanoate, hempseed oil, jojoba oil, lucerne oil, maize germ oil, marrow oil, millet oil, neopentylglycol dicaprylate/dicaprate, olive oil, palm oil, passionflower oil, pentaerythrityl tetrastearate, poppy oil, propylene glycol ricinoleate, rapeseed oil, rye oil, safflower oil, sesame oil, shea butter, soya oil, soybean oil, sweet almond oil, sunflower oil, sysymbrium oil, syzigium aromaticum oil, tea tree oil, walnut oil, wheat germ glycerides and wheat germ oil, an essential oil, PPG alkyl ethers, PPG-2 butyl ether, PPG-4 butyl ether, PPG-5 butyl ether, PPG-9 butyl ether, PPG-12 butyl ether, PPG-14 butyl ether, PPG-15 butyl ether, PPG-15 stearyl ether, PPG-16 butyl ether, PPG-17 butyl ether, PPG-18 butyl ether, PPG-20 butyl ether, PPG-22 butyl ether, PPG-24 butyl ether, PPG-26 butyl ether, PPG-30 butyl ether, PPG-33 butyl ether, PPG-40 butyl ether, PPG-52 butyl ether, PPG-53 butyl ether, PPG-10 cetyl ether, cetyl ether, PPG-30 cetyl ether, PPG-50 cetyl ether, PPG-30 isocetyl ether, lauryl ether, PPG-7 lauryl ether, PPG-2 methyl ether, PPG-3 methyl ether, PPG-myristyl ether, PPG-4 myristyl ether, PPG-10 oleyl ether, PPG-20 oleyl ether, oleyl ether, PPG-30 oleyl ether, PPG-37 oleyl ether, PPG-40 butyl ether, PPG-50 oleyl ether and PPG-11 stearyl ether. Preferred PPG alky ethers according to the present invention include PPG-15 stearyl ether, PPG-2 butyl ether and PPG-9-13 butyl ether, oils from animal origin, herring oil, cod-liver oil and salmon oil, a therapeutic oil, manuka oil, rosehip oil, tea tree oil, basil oil, camphor oil, cardamom oil, carrot oil, citronella oil, clary sage oil, clove oil, cypress oil, frankincense oil, ginger oil, grapefruit oil, hyssop oil, jasmine oil, lavender oil, lemon oil, mandarin oil, marjoram oil, myrrh oil, neroli oil, nutmeg oil, petitgrain oil, sage oil, tangerine oil, vanilla oil verbena oil , silicone oils, cyclomethicone, dimethicone, polyalkyl siloxane, polyaryl siloxane, polyalkylaryl siloxane, polyether siloxane copolymer, poly(dimethylsiloxane)-(diphenyl-siloxane) copolymer, dimethyl polysiloxane, epoxy-modified silicone oil, fatty acid-modified silicone oil, fluoro group-modified silicone oil, methylphenylpolysiloxane, phenyl trimethicone , polyether group-modified silicone oil cyclomethicone, cyclotetrasiloxane, cyclohexasiloxane, phyenyltrimethicone, Dow coming 246 Fluid (d6+d5) (cyclohexasiloxane & cyclopentasiloxane), Dow Coming 244 Fluid (cyclotetrasiloxane), Cyclomethicone 5-NF (cyclopentasiloxane), stearyl dimethicone, phenyltrimethicone, cetyl dimethicone, caprylyl methicone, PEG/PPG
18/18 dimethicone, or dimethiconol, capric/caprylic triglycerides, cyclomethicone;
isopropyl myristate, isopropyl palmitate, PPG- 15 stearyl ether;
octyldodecanol;
isohexadecanol, diisopropyl adipate; cetearyl octanoate; ; MCT oil; heavy mineral oil;
light mineral oil; coconut oil and soybean oil, an unsaturated or polyunsaturated oil, a diglyceride, a PPG alkyl ether or mixtures thereof.
18/18 dimethicone, or dimethiconol, capric/caprylic triglycerides, cyclomethicone;
isopropyl myristate, isopropyl palmitate, PPG- 15 stearyl ether;
octyldodecanol;
isohexadecanol, diisopropyl adipate; cetearyl octanoate; ; MCT oil; heavy mineral oil;
light mineral oil; coconut oil and soybean oil, an unsaturated or polyunsaturated oil, a diglyceride, a PPG alkyl ether or mixtures thereof.
17. The composition of claim 2, wherein the active agent is selected from a group consisting of calcitriol, mometasone fuorate, calcitriol and lidocaine.
18. The composition of claim 1, wherein the composition is short chain alcohol free and polyol free.
19. The composition of claim 2, for intradermal delivery of the active agent into the skin with minimal or negligible transdermal delivery.
20. The composition of claim 1, wherein the propellant is hydrocarbon propellant or a hydrofluorocarbon or another environmentally propellant.
21. The composition of claim 2, for use in eye infections.
22. The composition of claim 2, wherein the active agent is chemically stable for at least two months or for at least twelve months.
23. The composition of claim 1, wherein the wax further comprises hydrogenated caster oil or beeswax or mixtures thereof.
24. The composition of claim 2, wherein the active agent is compatible with the other ingredients.
25. A method of preventing or treating or alleviating a dermatological or mucosal disorder, comprising: applying a substantially surfactant free and adjuvant free foamable composition to a surface having or anticipated to have a dermatological or mucosal disorder in need of treatment, said composition comprising the composition of claim 2:
26. The method of claim 25, wherein the active agent is a placebo.
27. The method of claim 25, wherein the disorder is selected form the group consisting of abscess, acne, acne conglobata, acne fulminans, acne vulgaris, acne scars, acute febrile neutrophilic dermatosis, acute lymphangitis, allergic contact dermatitis, alopecia, athlete's foot, atopic dermatitis, bacterial skin infections, baldness, basal cell carcinoma, blisters, bromhidrosis, bullous pemphigoid, bum, calluses candidiasis, carbuncles, cellulitis, chemical bums, chicken pox, cholesteatoma, cholinergic urticaria, chronic effects of sunlight, cold sores, cold urticaria, comedones, corns, creeping eruption, cutaneous abscess, cutaneous larva migrans, cutaneous myiasis, dark spots, delusional parasitosis, Dercum disease, dermatitis, dermatitis herpetiformis, dermatological pain, dermatological inflammation, dermographism, dermatophytoses, drug eruptions and reactions, dyshidrotic eczema, ectodermal dysplasia, eczema, ecthyma, epidermoid cyst, epidermal necrolysis, erysipelas, erysipelas, erythrasma, exfoliative dermatitis, erythema multiforme, erythema nodosum, folliculitis, fungal nail infections, fungal skin infections, furuncles, gangrene, genital herpes, granuloma annulare, head lice, hidradenitis suppurativa, hives, folliculitis, hirsutism, hyperhidrosis, hypohidrosis, ichthyosis, impetigo, inflammatory acne, ingrown nails, intertrigo, irritant contact dermatitis, ischemic necrosis, itching, jock itch, Kaposi's sarcoma, keratosis pilaris, lichen simplex chronicus, lichen planus, lichen sclerosus, lymphadenitis, lymphadenitis, lymphangitis, malignant melanoma, mastocytosis, measles, melanoma, melanoma, miliaria, moles, molluscum contagiosum, MRSA, necrotizing subcutaneous infection, necrotizing fasciitis, necrotizing myositis, nodular papulopustular acne, non-inflammatory acne, nummular dermatitis, oral herpes, panniculitis, parapsoriasis paronychia, parasitic skin infections, pemphigus, photo-allergy, photo-damage, photo-irritation, photosensitivity, papules, pediculosis, perioral dermatitis, pimples, pityriasis rosea, pityriasis Lichenoides, pityriasis rosea, pityriasis rubra pilaris, poison ivy, poison oak post-operative or post-surgical skin conditions, pressure ulcers, pressure urticaria, pruritis, pseudofolliculitis barbae, psoriasis, PUPPP, purpura, pustules, pyogenic granuloma, rash, ringworm, rosacea, roseola, rubella, scabies, scalded skin syndrome, scarring, scleroderma, sebaceous cyst, seborrheic dermatitis, seborrheic keratosis, shingles, skin aging, skin cancer, skin neoplasia, skin neoplasms, skin rash, skin ulcers, squamous cell carcinoma, staphylococcal scalded skin syndrome, stasis dermatitis, Stevens-Johnson syndrome, sunburn, sun spots, thermal burns, tinea corporis, tinea cruris, tinea pedis, tinea versicolor, toxic epidermal necrolysis, trauma or injury to the skin, varicella zoster virus, vitamin D deficiency, viral skin infections, vitiligo, warts, water hives, wrinkles, xerosis, yeast skin infections and zoster.
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Families Citing this family (148)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8512718B2 (en) | 2000-07-03 | 2013-08-20 | Foamix Ltd. | Pharmaceutical composition for topical application |
IL152486A0 (en) | 2002-10-25 | 2003-05-29 | Meir Eini | Alcohol-free cosmetic and pharmaceutical foam carrier |
US20080031907A1 (en) * | 2002-10-25 | 2008-02-07 | Foamix Ltd. | Cosmetic and pharmaceutical foam |
US9265725B2 (en) | 2002-10-25 | 2016-02-23 | Foamix Pharmaceuticals Ltd. | Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof |
US20060018937A1 (en) * | 2002-10-25 | 2006-01-26 | Foamix Ltd. | Steroid kit and foamable composition and uses thereof |
US20070292359A1 (en) * | 2002-10-25 | 2007-12-20 | Foamix Ltd. | Polypropylene glycol foamable vehicle and pharmaceutical compositions thereof |
US20060233721A1 (en) * | 2002-10-25 | 2006-10-19 | Foamix Ltd. | Foam containing unique oil globules |
US9668972B2 (en) | 2002-10-25 | 2017-06-06 | Foamix Pharmaceuticals Ltd. | Nonsteroidal immunomodulating kit and composition and uses thereof |
US7700076B2 (en) | 2002-10-25 | 2010-04-20 | Foamix, Ltd. | Penetrating pharmaceutical foam |
US20050271596A1 (en) * | 2002-10-25 | 2005-12-08 | Foamix Ltd. | Vasoactive kit and composition and uses thereof |
US20080138296A1 (en) | 2002-10-25 | 2008-06-12 | Foamix Ltd. | Foam prepared from nanoemulsions and uses |
US20050205086A1 (en) * | 2002-10-25 | 2005-09-22 | Foamix Ltd. | Retinoid immunomodulating kit and composition and uses thereof |
US8900554B2 (en) | 2002-10-25 | 2014-12-02 | Foamix Pharmaceuticals Ltd. | Foamable composition and uses thereof |
AU2003279493B2 (en) * | 2002-10-25 | 2009-08-20 | Foamix Pharmaceuticals Ltd. | Cosmetic and pharmaceutical foam |
US7820145B2 (en) | 2003-08-04 | 2010-10-26 | Foamix Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US20080206161A1 (en) * | 2002-10-25 | 2008-08-28 | Dov Tamarkin | Quiescent foamable compositions, steroids, kits and uses thereof |
US9211259B2 (en) | 2002-11-29 | 2015-12-15 | Foamix Pharmaceuticals Ltd. | Antibiotic kit and composition and uses thereof |
US10117812B2 (en) | 2002-10-25 | 2018-11-06 | Foamix Pharmaceuticals Ltd. | Foamable composition combining a polar solvent and a hydrophobic carrier |
US7704518B2 (en) | 2003-08-04 | 2010-04-27 | Foamix, Ltd. | Foamable vehicle and pharmaceutical compositions thereof |
US7575739B2 (en) | 2003-04-28 | 2009-08-18 | Foamix Ltd. | Foamable iodine composition |
US8795693B2 (en) * | 2003-08-04 | 2014-08-05 | Foamix Ltd. | Compositions with modulating agents |
US8486374B2 (en) | 2003-08-04 | 2013-07-16 | Foamix Ltd. | Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses |
WO2005011567A2 (en) * | 2003-08-04 | 2005-02-10 | Foamix Ltd. | Foam carrier containing amphiphilic copolymeric gelling agent |
JP2005310310A (en) * | 2004-04-23 | 2005-11-04 | Sanyo Electric Co Ltd | Tracking balance adjustment device |
US20080152596A1 (en) * | 2005-07-19 | 2008-06-26 | Foamix Ltd. | Polypropylene glycol foamable vehicle and pharmaceutical compositions thereof |
MX2009002536A (en) * | 2006-09-08 | 2009-04-14 | Foamix Ltd | Colored or colorable foamable composition and foam. |
US20080260655A1 (en) | 2006-11-14 | 2008-10-23 | Dov Tamarkin | Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses |
US8636982B2 (en) | 2007-08-07 | 2014-01-28 | Foamix Ltd. | Wax foamable vehicle and pharmaceutical compositions thereof |
WO2009069006A2 (en) * | 2007-11-30 | 2009-06-04 | Foamix Ltd. | Foam containing benzoyl peroxide |
WO2009090495A2 (en) | 2007-12-07 | 2009-07-23 | Foamix Ltd. | Oil and liquid silicone foamable carriers and formulations |
US8518376B2 (en) | 2007-12-07 | 2013-08-27 | Foamix Ltd. | Oil-based foamable carriers and formulations |
EP2242476A2 (en) | 2008-01-14 | 2010-10-27 | Foamix Ltd. | Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses |
CA2760186C (en) | 2009-04-28 | 2019-10-29 | Foamix Ltd. | Foamable vehicle and pharmaceutical compositions comprising aprotic polar solvents and uses thereof |
WO2011013008A2 (en) | 2009-07-29 | 2011-02-03 | Foamix Ltd. | Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses |
CA2769625C (en) | 2009-07-29 | 2017-04-11 | Foamix Ltd. | Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses |
US9364485B2 (en) | 2009-08-31 | 2016-06-14 | Dr. Reddy's Laboratories Ltd. | Topical formulations comprising a steroid |
US9849142B2 (en) | 2009-10-02 | 2017-12-26 | Foamix Pharmaceuticals Ltd. | Methods for accelerated return of skin integrity and for the treatment of impetigo |
MX359879B (en) | 2009-10-02 | 2018-10-12 | Foamix Pharmaceuticals Ltd | Topical tetracycline compositions. |
US20120076766A1 (en) * | 2010-04-21 | 2012-03-29 | Phillips D Howard | Topical drug delivery system with dual carriers |
US20130053353A1 (en) * | 2010-05-04 | 2013-02-28 | Foamix Ltd. | Compositions, gels and foams with rheology modulators and uses |
US20140221320A1 (en) * | 2011-07-08 | 2014-08-07 | The Research Foundation For The State University Of New York | Topical minocycline ointment for suppression of allergic skin responses |
EP2731590B1 (en) | 2011-07-13 | 2018-05-23 | The Foundry, LLC | Methods and apparatus for delivering a therapeutic agent to nasopharyngeal mucosa targets |
US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
JP6285866B2 (en) | 2011-11-23 | 2018-02-28 | セラピューティックスエムディー インコーポレーテッドTherapeuticsmd, Inc. | Natural complex hormone replacement preparations and therapies |
EA027534B1 (en) * | 2012-02-05 | 2017-08-31 | ТиЮСиСи ТЕКНОЛОДЖИ, ЭлЭлСи | Earth metal peroxide fluidized compositions |
IL225246A0 (en) * | 2012-03-15 | 2013-06-27 | Meir Eini | Methods for accelerated return of skin integrity and for the treatment of impetigo |
EP3427721A1 (en) * | 2012-05-18 | 2019-01-16 | Genentech, Inc. | High-concentration monoclonal antibody formulations |
US20130338122A1 (en) | 2012-06-18 | 2013-12-19 | Therapeuticsmd, Inc. | Transdermal hormone replacement therapies |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
RU2504383C1 (en) * | 2012-07-10 | 2014-01-20 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Омский государственный аграрный университет имени П.А. Столыпина" | Method of treating acute postpartum endometritis in cows |
US10507245B2 (en) | 2012-07-19 | 2019-12-17 | Luis Felipe Vejarano Restrepo | Ophthalmic formulation and method for ameliorating presbyopia |
AU2013295645B2 (en) * | 2012-07-27 | 2017-08-24 | Glia Llc | Compositions and treatment for eye diseases and disorders |
PT106679B (en) | 2012-11-27 | 2015-03-25 | Hovione Farmaciencia Sa | TOPICAL FORMULATIONS OF TETRACYCLINES, THEIR PREPARATION AND USES |
US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
MX359686B (en) * | 2013-03-15 | 2018-10-05 | Nanorx Inc | Metadichol r liquid and gel nanoparticle formulations. |
CA2906594C (en) | 2013-03-15 | 2019-01-08 | Leading Edge Innovations, LLC | Substantially surfactant-free, submicron dispersions of hydrophobic agents containing high levels of water miscible solvent |
US20140322428A1 (en) | 2013-03-15 | 2014-10-30 | Leading Edge Innovations, LLC | Compositions having an oil-in-water dispersion of submicron particles to enhance foods and beverages |
DE102013217242A1 (en) * | 2013-08-29 | 2015-03-05 | Beiersdorf Ag | Emulsifier-free, skin-conditioning, cosmetic or dermatological preparation with peeling active ingredients |
WO2015066717A1 (en) | 2013-11-04 | 2015-05-07 | BioPharmX, Inc. | Dosage form comprising an active ingredient and a plurality of solid porous microcarriers |
US9226890B1 (en) | 2013-12-10 | 2016-01-05 | Englewood Lab, Llc | Polysilicone base for scar treatment |
US20170007507A1 (en) * | 2014-02-07 | 2017-01-12 | Coty Inc. | Free standing color cosmetic stick |
WO2015126624A1 (en) * | 2014-02-18 | 2015-08-27 | Elevance Renewable Sciences, Inc. | Branched-chain esters and methods of making and using the same |
US20160184431A1 (en) | 2014-03-11 | 2016-06-30 | Promius Pharma Llc | Topical compositions comprising a corticosteroid |
MX2016011842A (en) * | 2014-03-11 | 2017-02-02 | Promius Pharma Llc | Topical corticosteroid compositions. |
AU2015264003A1 (en) | 2014-05-22 | 2016-11-17 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
MX2016013693A (en) | 2014-07-29 | 2017-10-31 | Therapeuticsmd Inc | Transdermal cream. |
WO2016048274A1 (en) | 2014-09-23 | 2016-03-31 | Colgate-Palmolive Company | Non-greasy personal care compositions |
US9895311B2 (en) | 2014-09-25 | 2018-02-20 | Pharmiva Ab | Foam-forming compositions and methods for delivering an active to a body cavity |
FR3026641B1 (en) * | 2014-10-02 | 2018-01-26 | Pierre Fabre Dermo-Cosmetique | COSMETIC AND / OR PHARMACEUTICAL COMPOSITION IN THE FORM OF DISPERSION, PREPARATION METHOD AND USE FOR THE TREATMENT OF SKIN |
CN104352527A (en) * | 2014-10-20 | 2015-02-18 | 中山百鸥医药科技有限公司 | Application of cod liver oil to the treatment of gynaecopathia |
CA2966325A1 (en) | 2014-10-31 | 2016-05-06 | Pomega, Inc. | Formulations containing pomegranate seed oil, rosa canina fruit oil and inula viscosa oleoresin or extract. |
KR102332621B1 (en) * | 2014-11-21 | 2021-12-01 | 삼성전자주식회사 | Signal Receiving and Transmitting circuit and electronic device including the same |
DE102015121112A1 (en) * | 2014-12-23 | 2016-06-23 | Kalle Gmbh | Biocide-free, pre-moistened sponge cloth |
CN107427445B (en) | 2015-02-19 | 2021-03-02 | 荷兰联合利华有限公司 | Quick-rinsing cleaning composition |
JP2018506554A (en) * | 2015-02-25 | 2018-03-08 | サン、ファーマ、アドバンスト、リサーチ、カンパニー、リミテッドSun Pharma Advanced Research Company Limited | Nanoparticle composition |
TW201705962A (en) | 2015-03-23 | 2017-02-16 | 生物製藥X公司 | Pharmaceutical tetracycline composition for dermatological use |
US10952950B2 (en) | 2015-04-23 | 2021-03-23 | The Procter And Gamble Company | Concentrated personal cleansing compositions and methods |
WO2016172472A1 (en) | 2015-04-23 | 2016-10-27 | The Procter & Gamble Company | Concentrated personal cleansing compositions and uses |
EP3285728B1 (en) | 2015-04-23 | 2019-12-18 | The Procter and Gamble Company | Concentrated personal cleansing compositions and methods |
CN107530247B (en) | 2015-04-23 | 2021-09-07 | 宝洁公司 | Concentrated personal cleansing compositions |
KR101875997B1 (en) * | 2015-05-04 | 2018-07-06 | 엔 앤드 엔 파마세우티칼스 인크. | Method for treating shingles with n-methanocarbathymidine |
WO2016181998A1 (en) * | 2015-05-12 | 2016-11-17 | ライオン株式会社 | Ophthalmologic composition |
BR112017024934A8 (en) | 2015-05-21 | 2021-03-30 | Dermavant Sciences GmbH | topical pharmaceutical compositions |
US11617724B2 (en) | 2015-05-21 | 2023-04-04 | Dermavant Sciences GmbH | Topical pharmaceutical compositions |
DE102015209752A1 (en) | 2015-05-28 | 2016-12-01 | Beiersdorf Ag | Sprayable highly viscous cosmetic preparation |
US20200405637A1 (en) * | 2015-06-19 | 2020-12-31 | Global Health Solutions Llc | Oil-based wound care compositions and methods |
CN108136027A (en) * | 2015-06-19 | 2018-06-08 | 全球健康方案有限责任公司 | For the delivery system based on vaseline of active constituent |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
US20190307778A1 (en) * | 2015-08-20 | 2019-10-10 | Foamix Pharmaceuticals Ltd. | Tetracycline management of egfr inhibitor associated dermatoses |
JP6856631B2 (en) | 2015-09-16 | 2021-04-07 | ディーエフビー ソリア リミテッド ライアビリティ カンパニー | Delivery of drug nanoparticles and their use |
US9617504B2 (en) * | 2015-09-22 | 2017-04-11 | Scott Robert Sorenson | Non-medicated personal care cleansing solution and a method of synthesizing the same |
US20170121098A1 (en) | 2015-11-02 | 2017-05-04 | American Sterilizer Company | Non-aspirating transport gel dispenser |
US11931379B2 (en) * | 2015-12-22 | 2024-03-19 | Johnson & Johnson Consumer Inc. | Stable foaming composition and method of use |
JP7026914B2 (en) | 2016-01-29 | 2022-03-01 | 日産化学株式会社 | Transdermal absorption composition with controlled release of water-soluble active ingredient |
US10286077B2 (en) | 2016-04-01 | 2019-05-14 | Therapeuticsmd, Inc. | Steroid hormone compositions in medium chain oils |
WO2017173071A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical composition |
CN109219442A (en) * | 2016-04-04 | 2019-01-15 | Omeza有限公司 | Fish oil topical composition |
JP2019513888A (en) * | 2016-04-15 | 2019-05-30 | ヌシル テクノロジー エルエルシー | Surfactant-free silicone emulsion |
BR112018073097B1 (en) | 2016-05-11 | 2022-05-17 | Bayer Healthcare Llc | Foaming formulation, methods for making and using it, and formulation |
WO2017197196A1 (en) | 2016-05-11 | 2017-11-16 | Bayer Healthcare Llc | Whipped gel formulations |
CN105833279B (en) * | 2016-05-30 | 2021-06-22 | 傅远桥 | External-use medicine composition for treating various wound surfaces of skin and preparation method thereof |
CA2978573A1 (en) | 2016-09-08 | 2018-03-08 | Foamix Pharmaceuticals Ltd. | Compositions and methods for treating rosacea and acne |
GB201615693D0 (en) | 2016-09-15 | 2016-11-02 | Combinatorx Infection Ltd | Combinations |
EP3528777B1 (en) | 2016-10-21 | 2021-09-01 | The Procter & Gamble Company | Skin cleansing compositions and methods |
US11185486B2 (en) | 2016-10-21 | 2021-11-30 | The Procter And Gamble Company | Personal cleansing compositions and methods |
JP7020941B2 (en) * | 2017-02-03 | 2022-02-16 | 日本精化株式会社 | Cosmetics |
US11602303B2 (en) * | 2017-02-10 | 2023-03-14 | Mauricio De Maio Domingos | Methods and systems for preventing, correcting, transforming, and modifying facial, aesthetics, and consulting patients regarding the same |
US10675231B2 (en) * | 2017-02-17 | 2020-06-09 | The Procter & Gamble Company | Packaged personal cleansing product |
ES2955884T3 (en) | 2017-03-15 | 2023-12-07 | Dfb Soria Llc | Topical therapy for the treatment of skin malignancies with taxane nanoparticles |
US11383084B2 (en) * | 2017-04-27 | 2022-07-12 | Palo Alto Investors | Treatment of dermatological conditions via neuromodulation |
MX2019013454A (en) | 2017-05-11 | 2020-08-03 | Beiersdorf Ag | Gel formulations. |
KR20200009079A (en) | 2017-05-23 | 2020-01-29 | 파르미바 아베 | Foam-forming composition for delivering the active agent to the body cavity |
WO2018234865A1 (en) * | 2017-06-20 | 2018-12-27 | Foamix Pharmaceuticals Ltd. | Stable topical tetracycline compositions |
JP2020536614A (en) | 2017-10-04 | 2020-12-17 | ニューマ・リスパイラトリー・インコーポレイテッド | In-line droplet delivery device and usage that is electrically operated by breathing |
US11771852B2 (en) | 2017-11-08 | 2023-10-03 | Pneuma Respiratory, Inc. | Electronic breath actuated in-line droplet delivery device with small volume ampoule and methods of use |
FR3075532A1 (en) * | 2017-12-14 | 2019-06-21 | Orange | METHOD FOR GENERATING A MULTI-CARRIER SIGNAL, DEMODULATION METHOD, COMPUTER PROGRAM PRODUCT, AND CORRESPONDING DEVICES |
US11191740B2 (en) | 2018-01-07 | 2021-12-07 | Dr. Reddy's Laboratories Ltd. | Methods for treating inflammatory skin conditions |
CN111655233A (en) * | 2018-01-26 | 2020-09-11 | 宝洁公司 | Methods and compositions for reducing vaginal dryness sensation |
WO2019178024A1 (en) | 2018-03-16 | 2019-09-19 | Dfb Soria, Llc | Topical therapy for the treatment of cervical intraepithelial neoplasia (cin) and cervical cancer using nanoparticles of taxanes |
US10285998B1 (en) | 2018-04-04 | 2019-05-14 | The Menopause Method, Inc. | Composition and method to aid in hormone replacement therapy |
GB201813876D0 (en) | 2018-08-24 | 2018-10-10 | Antibiotx As | Treatment |
BR112021008417A2 (en) | 2018-11-02 | 2021-09-14 | UNION therapeutics A/S | HALOGENATED SALICYLANYLIDES TO TREAT DERMATITIS SYMPTOMS |
WO2020089467A1 (en) | 2018-11-02 | 2020-05-07 | UNION therapeutics A/S | Dosage regimen |
US11497718B2 (en) | 2018-11-13 | 2022-11-15 | Dermavant Sciences GmbH | Use of tapinarof for the treatment of atopic dermatitis |
US10588871B1 (en) | 2019-06-28 | 2020-03-17 | Nexzol Pharma, Inc. | Transdermal formulation for the treatment of pain and/or inflammation |
WO2020263643A1 (en) * | 2019-06-28 | 2020-12-30 | Nexzol Pharma, Inc. | Transdermal formulations |
US20230346805A1 (en) | 2019-07-31 | 2023-11-02 | Journey Medical Corporation | Compositions and methods and uses thereof |
BE1027141B1 (en) | 2019-08-30 | 2020-10-15 | Oystershell Nv | POLYISOBUTENE FOR USE IN THE TREATMENT OR PREVENTION OF INFECTION BY Arthropods |
US11590073B2 (en) | 2020-06-09 | 2023-02-28 | The Procter & Gamble Company | Methods and compositions for reducing the feeling of vaginal dryness |
US20210401794A1 (en) * | 2020-06-30 | 2021-12-30 | Np Pharma Holdings, Llc | Methods of Using Cannabinoid Compositions for Inducing and Promoting Sleep |
WO2022122136A1 (en) | 2020-12-09 | 2022-06-16 | Symrise Ag | Compositions comprising one or more (bio)-alkanediols with antioxidants |
IT202100002126A1 (en) * | 2021-02-02 | 2022-08-02 | Binar S R L | HYPOALLERGENIC FOOTWEAR AND METHOD TO PREVENT ALLERGIC CONTACT DERMATITIS ACD |
CN112829395B (en) * | 2021-02-05 | 2023-07-04 | 义乌市皓祺服饰有限公司 | Preparation method of waterproof breathable jacket fabric |
WO2022256101A1 (en) * | 2021-06-04 | 2022-12-08 | Demary Dean | Systems, devices, and/or methods for human hygiene |
WO2022271848A1 (en) | 2021-06-22 | 2022-12-29 | Pneuma Respiratory, Inc. | Droplet delivery device with push ejection |
EP4108234A1 (en) * | 2021-06-25 | 2022-12-28 | RaDes GmbH | Topical pharmaceutical formulation |
WO2023064477A1 (en) * | 2021-10-13 | 2023-04-20 | Pneuma Respiratory, Inc. | Compositions for delivery of cannabinoids |
WO2023097309A1 (en) | 2021-11-29 | 2023-06-01 | Ironwood Pharmaceuticals, Inc. | Pharmaceutical compositions for the treatment of visceral pain |
EP4265708A1 (en) * | 2022-04-19 | 2023-10-25 | Cargill, Incorporated | Process for solvent recovery in vegetable oil extraction |
CN115463091B (en) * | 2022-10-27 | 2023-04-07 | 新基元(北京)医药科技有限公司 | Minocycline foaming agent with improved stability |
CN115554243B (en) * | 2022-11-11 | 2023-03-03 | 新基元(北京)医药科技有限公司 | Minocycline foam for treating acne rosacea |
Family Cites Families (1205)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1159250A (en) | 1914-05-01 | 1915-11-02 | Frank Moulton | Vaginal irrigator. |
US1666684A (en) | 1926-01-15 | 1928-04-17 | Carstens Mfg Co H | Vaginal douche |
US1924972A (en) | 1929-04-15 | 1933-08-29 | Carl J Beckert | Stabilized egg product |
US2085733A (en) | 1935-07-15 | 1937-07-06 | John C Bird | Shaving cream |
US2390921A (en) | 1943-03-23 | 1945-12-11 | Ethel Hudson Clark | Applicator for facial creams |
US2524590A (en) | 1946-04-22 | 1950-10-03 | Carsten F Boe | Emulsion containing a liquefied propellant gas under pressure and method of spraying same |
US2586287A (en) | 1948-12-11 | 1952-02-19 | Colagte Palmolive Peet Company | Aluminum sulfamate antiperspirant preparation |
US2617754A (en) | 1949-08-29 | 1952-11-11 | Procter & Gamble | Cosmetic cream |
US3062715A (en) | 1953-11-18 | 1962-11-06 | George S Pfaus | Vaginal tablet |
US2767712A (en) | 1954-03-01 | 1956-10-23 | Neil S Waterman | Medicinal applicator |
GB808104A (en) | 1955-01-04 | 1959-01-28 | Udylite Res Corp | Electrodeposition of copper from aqueous alkaline cyanide solutions |
GB808105A (en) | 1956-06-15 | 1959-01-28 | Ici Ltd | New pharmaceutical compositions |
US3092555A (en) | 1958-04-21 | 1963-06-04 | Roy H Horn | Relatively collapsible aerosol foam compositions |
US3144386A (en) | 1958-05-09 | 1964-08-11 | Merck & Co Inc | Mastitis aerosol foam |
US2968628A (en) | 1958-10-17 | 1961-01-17 | Shulton Inc | Propellant composition |
US3178352A (en) | 1959-02-27 | 1965-04-13 | Erickson Roy | Shaving method and composition therefor |
US3141821A (en) | 1959-03-17 | 1964-07-21 | Lehn & Fink Products Corp | Synergistic combination of alkyl sulfonates, alkylaryl sulfonates and topical antibacterial agents for local antisepsis |
US3004894A (en) | 1959-04-07 | 1961-10-17 | Upjohn Co | Therapeutic composition comprising tetracycline and a dioxolane |
GB922930A (en) | 1959-09-21 | 1963-04-03 | Sunnen Joseph | Spermicidal composition and method of making same |
US3142420A (en) | 1959-11-09 | 1964-07-28 | Neotechnic Eng Ltd | Metering dispenser for aerosol with fluid pressure operated piston |
US3092255A (en) | 1960-02-05 | 1963-06-04 | Robert F Hohman | Sorting apparatus |
US3067784A (en) | 1960-04-14 | 1962-12-11 | Esta Medical Lab Inc | Adapter connecting aerosol container valve stem to dispenser for filling said dispenser |
NL270627A (en) | 1960-10-26 | |||
US3154075A (en) | 1960-11-02 | 1964-10-27 | Norwich Pharma Co | Vaginal applicator |
GB998490A (en) | 1961-06-03 | 1965-07-14 | Albert Fritz Albach | A foam projector |
DE1926796U (en) | 1961-10-12 | 1965-11-11 | Heidolph Elektro K G | FAN. |
BE624833A (en) | 1962-02-28 | |||
US3261695A (en) | 1962-12-24 | 1966-07-19 | Gen Foods Corp | Process for preparing dehydrated foods |
US3330730A (en) | 1962-08-03 | 1967-07-11 | Colgate Palmolive Co | Pressurized emulsion quick breaking foam compositions |
US3252859A (en) | 1962-10-24 | 1966-05-24 | Masti Kure Company Inc | Colloidal silica-oil composition and method of using same |
US3244589A (en) | 1962-10-26 | 1966-04-05 | Sunnen | Alkyl phenoxy polyethoxy ether spermicidal aerosol |
US3298919A (en) | 1962-12-26 | 1967-01-17 | Dow Corning | Shaving cream containing polysiloxanes |
US3383280A (en) | 1963-01-09 | 1968-05-14 | Miles Lab | Dermatological abradant stick-type applicator |
FR1355607A (en) | 1963-01-22 | 1964-03-20 | Improvements to cannula probes and their applications | |
US3149543A (en) | 1963-03-04 | 1964-09-22 | Ingersoll Rand Co | Non-lubricated piston |
GB1026831A (en) | 1963-05-31 | 1966-04-20 | Mediline Ag | Preparations for use in feminine hygiene |
US3824303A (en) | 1963-07-24 | 1974-07-16 | Yardley Of London Inc | Collapsible foam pre-electric shave lotion containing diester lubricants |
GB1081949A (en) | 1963-08-12 | 1967-09-06 | Avon Prod Inc | Improvements in cosmetic mask |
US3333333A (en) | 1963-08-14 | 1967-08-01 | Rca Corp | Method of making magnetic material with pattern of embedded non-magnetic material |
US3236457A (en) | 1963-08-21 | 1966-02-22 | John R Kennedy | Composite spray container assembly |
US3263867A (en) | 1963-12-26 | 1966-08-02 | Valve Corp Of America | Metering button-type aerosol actuator |
US3395214A (en) | 1964-01-09 | 1968-07-30 | Scholl Mfg Co Inc | Antiperspirant composition providing a readily collapsible sprayable foam |
US3278093A (en) | 1964-01-13 | 1966-10-11 | Valve Corp Of America | Metering and non-metering aerosol actuator button |
GB1052724A (en) | 1964-04-27 | |||
US3303970A (en) | 1964-07-14 | 1967-02-14 | Jerome Marrow | Device for simultaneously dispensing from plural sources |
US3395215A (en) | 1964-10-15 | 1968-07-30 | Colgate Palmolive Co | Pressurized lotion composition |
US3384541A (en) | 1964-10-28 | 1968-05-21 | William G. Clark | Spermicidal vaginal pharmaceutical concentrate for producing nonaqueous foam with aerosol propellants |
US3263869A (en) | 1964-11-03 | 1966-08-02 | Calmar Inc | Liquid dispenser with overcap |
US3342845A (en) | 1964-11-05 | 1967-09-19 | Upjohn Co | Terphenyl triisocyanates |
US3419658A (en) | 1965-01-25 | 1968-12-31 | Du Pont | Nonaqueous aerosol foams containing mineral oil |
US3346451A (en) | 1965-01-27 | 1967-10-10 | S E Massengill Company | Concentrated liquid lactic acid douche preparation containing aromatics |
US3301444A (en) | 1965-08-12 | 1967-01-31 | Oel Inc | Aerosol metering valve |
US3456052A (en) | 1965-09-28 | 1969-07-15 | Garrett Lab Inc | Aerosol composition containing butoxymonoether of a polyoxyalkylene glycol |
GB1121358A (en) | 1965-10-21 | 1968-07-24 | Bristol Myers Co | Aerosol manufacture |
US3849569A (en) | 1965-12-02 | 1974-11-19 | Glaxo Lab Ltd | Composition containing procaine penicillin |
BE692228A (en) | 1966-01-10 | 1967-07-05 | ||
US3401849A (en) | 1966-05-24 | 1968-09-17 | Robert L. Weber | Low force metering valve |
US3886084A (en) | 1966-09-29 | 1975-05-27 | Champion Int Corp | Microencapsulation system |
US3377004A (en) | 1966-10-03 | 1968-04-09 | Gen Mills Inc | Metered dispensing container |
GB1201918A (en) | 1966-12-21 | 1970-08-12 | Bespak Industries Ltd | Improvements in or relating to valves for pressurised dispensers |
US3527559A (en) | 1967-01-05 | 1970-09-08 | Standard Pharmacal Corp | Dense aqueous aerosol foam depilatory compositions containing a mixture of alkaline metal and alkali metal thioglycolates and a fatty alcohol-alkylene oxide wax emulsifying agent |
US3366494A (en) | 1967-02-15 | 1968-01-30 | Du Pont | Pressurized aerosol food emulsions |
US3561262A (en) | 1967-10-26 | 1971-02-09 | Magnaflux Corp | Water soluble developer |
US3540448A (en) | 1968-01-17 | 1970-11-17 | Joseph Sunnen | Rechargeable applicator for dispensing substances in a foam condition |
DE1926796A1 (en) | 1968-05-27 | 1970-03-19 | Dudiuyt Jean Paul | Aerosol compsn. and container |
US3563098A (en) | 1968-06-28 | 1971-02-16 | Rex Chainbelt Inc | Automatic quick release mechanism |
US3559890A (en) | 1968-09-03 | 1971-02-02 | William R Brooks | Foam dispenser |
US3878118A (en) | 1968-09-06 | 1975-04-15 | Wilkinson Sword Ltd | Self-heating chemical compositions |
US3667461A (en) | 1968-11-05 | 1972-06-06 | Paul A Zamarra | Disposable syringe |
CA975500A (en) | 1969-02-06 | 1975-09-30 | Joseph G. Spitzer | Structures such as applicator pads for cleaning and other purposes, propellant compositions for forming the same, and process |
US3866800A (en) | 1969-02-12 | 1975-02-18 | Alberto Culver Co | Non-pressurized package containing self-heating products |
US3966090A (en) | 1969-02-17 | 1976-06-29 | Dart Industries Inc. | Package for dispensing an antiseptic composition |
US4001391A (en) | 1969-04-18 | 1977-01-04 | Plough, Inc. | Means for depositing aerosol sprays in buttery form |
US3819524A (en) | 1969-06-17 | 1974-06-25 | Colgate Palmolive Co | Cosmetic composition for thermal dispensing |
US3577518A (en) | 1969-07-18 | 1971-05-04 | Nat Patent Dev Corp | Hydrophilic hairspray and hair setting preparations |
US3787566A (en) | 1969-07-29 | 1974-01-22 | Holliston Labor Inc | Disinfecting aerosol compositions |
BE759520A (en) | 1969-11-28 | 1971-04-30 | Aspro Nicholas Ltd | ASPIRIN COMPOSITIONS |
GB1353381A (en) | 1971-02-04 | 1974-05-15 | Wilkinson Sword Ltd | Substituted p-menthanes and compositions containing them |
GB1351761A (en) | 1971-02-04 | 1974-05-01 | Wilkinson Sword Ltd | Substituted p-menthane carboxamides and compositions containing them |
GB1351762A (en) | 1971-02-14 | 1974-05-01 | Wilkinson Sword Ltd | Tobacco and tobacco-containing manufactures |
CA958338A (en) | 1971-03-08 | 1974-11-26 | Chung T. Shin | Antiperspirant powder aerosol compositions containing aluminum chloride and water soluble aluminum compounds and methods of preparation |
US3770648A (en) | 1971-07-12 | 1973-11-06 | Bristol Myers Co | Anhydrous aerosol foam |
US3912667A (en) | 1971-09-13 | 1975-10-14 | Spitzer Joseph G | Structures such as applicator pads for cleaning and other purposes, propellant compositions for forming the same and process |
BE788788A (en) | 1971-09-13 | 1973-03-13 | Treuhandvereinigung Ag | PRODUCT FOR PRESERVING, PROMOTING AND RESTORING HAIR AND METHOD OF MANUFACTURING THIS PRODUCT |
SE358308B (en) | 1971-11-26 | 1973-07-30 | Pharmacia Ab | |
US3997467A (en) | 1971-11-26 | 1976-12-14 | Pharmacia Aktiebolag | Foam forming composition |
CH569128B5 (en) | 1971-12-30 | 1975-11-14 | Ciba Geigy Ag | |
JPS4892282U (en) | 1972-02-05 | 1973-11-06 | ||
US3963833A (en) | 1972-06-02 | 1976-06-15 | Colgate-Palmolive Company | Antiperspirant composition and method containing a dihydro-benzofuran and an astringent metal salt |
US3841525A (en) | 1972-06-14 | 1974-10-15 | N Siegel | Aerosol spray device with cam activator |
US3849580A (en) | 1972-09-05 | 1974-11-19 | American Home Prod | Aerosol dispensing system for anhydrous edible fat compositions |
US3751562A (en) | 1972-09-22 | 1973-08-07 | Princeton Biomedix | Medicated gelled oils |
US3970584A (en) | 1973-02-14 | 1976-07-20 | S. C. Johnson & Son, Inc. | Aerosol package containing a foam-forming emulsion and propellent system |
US4439416A (en) | 1973-03-23 | 1984-03-27 | Colgate-Palmolive Company | Self-heating shaving composition |
GB1423179A (en) | 1973-05-16 | 1976-01-28 | Wilkinson Sword Ltd | Pressurised shaving foam dispensers |
YU36328B (en) | 1973-07-18 | 1983-06-30 | Elastin Werk Ag | Method of manufacturing red foils for packing sausages |
US4110426A (en) | 1973-07-24 | 1978-08-29 | Colgate-Palmolive Company | Method of treating skin and hair with a self-heated cosmetic |
US3865275A (en) | 1973-07-30 | 1975-02-11 | Raymond Lee Organization Inc | Apparatus for operating an aerosol can |
US3929985A (en) | 1974-01-18 | 1975-12-30 | Richardson Merrell Inc | Anhydrous candicidin foam compositions |
DE2501548A1 (en) | 1974-01-25 | 1975-07-31 | Procter & Gamble | ORAL TREATMENT PRODUCTS |
GB1457671A (en) | 1974-01-31 | 1976-12-08 | Wilkinson Sword Ltd | Flavour |
US3923970A (en) | 1974-03-29 | 1975-12-02 | Carter Wallace | Stable aerosol shaving foams containing mineral oil |
US3962150A (en) | 1974-04-10 | 1976-06-08 | Richardson-Merrell Inc. | Foam producing cleansing compositions |
US3953591A (en) | 1974-04-29 | 1976-04-27 | The Procter & Gamble Company | Fatty acid, polysiloxane and water-soluble polymer containing skin conditioning emulsion |
US3966632A (en) | 1974-06-06 | 1976-06-29 | G. D. Searle & Co. | Vegetable oil emulsion |
US4145411A (en) | 1974-09-05 | 1979-03-20 | Colgate-Palmolive Company | Pressurized foaming shaving composition |
JPS5729213B2 (en) | 1974-11-12 | 1982-06-21 | ||
US4052513A (en) | 1974-12-13 | 1977-10-04 | Plough, Inc. | Stable topical anesthetic compositions |
US3952916A (en) | 1975-01-06 | 1976-04-27 | Warner-Lambert Company | Automatic dispenser for periodically actuating an aerosol container |
US3970219A (en) | 1975-03-03 | 1976-07-20 | Spitzer Joseph G | Aerosol containers for foaming and delivering aerosols and process |
US4019657A (en) | 1975-03-03 | 1977-04-26 | Spitzer Joseph G | Aerosol containers for foaming and delivering aerosols |
US4018396A (en) | 1975-05-05 | 1977-04-19 | Bechtel International Corporation | Embedded housing for ore crusher |
US3993224A (en) | 1975-09-08 | 1976-11-23 | Aerosol Investments, Ltd. | Spout for two-component resin dispenser |
DE2608226A1 (en) | 1976-02-28 | 1977-09-08 | Haarmann & Reimer Gmbh | AGENTS WITH PHYSIOLOGICAL COOLING EFFECT |
US4100426A (en) | 1976-03-10 | 1978-07-11 | Square D Company | Load controlling means |
IL49491A (en) | 1976-04-29 | 1979-09-30 | Rosenberg Peretz | Quickly-attachable connector for plastic pipes |
US4102995A (en) | 1976-05-13 | 1978-07-25 | Westwood Pharmaceuticals Inc. | Tar gel formulation |
US4124149A (en) | 1976-07-19 | 1978-11-07 | Spitzer Joseph G | Aerosol container with position-sensitive shut-off valve |
CA1089368A (en) | 1976-08-02 | 1980-11-11 | Daniel C. Geary | Polyethoxylated fatty alcohol in antiperspirant sticks |
IL52045A (en) | 1976-08-25 | 1979-12-30 | Mundipharma Ag | Sprayable germicidal foam compositions |
US4252787A (en) | 1976-12-27 | 1981-02-24 | Cambridge Research And Development Group | Anti-fertility composition and method |
US4310510A (en) | 1976-12-27 | 1982-01-12 | Sherman Kenneth N | Self administrable anti-fertility composition |
US4083974A (en) | 1977-03-07 | 1978-04-11 | The Upjohn Company | Topical steroidal anti-inflammatory preparations containing polyoxypropylene 15 stearyl ether |
JPS5744429Y2 (en) | 1977-04-14 | 1982-10-01 | ||
IT1114950B (en) | 1977-12-30 | 1986-02-03 | Porro Marcella | COMPOSITIONS FOR ACNE TREATMENT AND THERAPY |
US4386104A (en) | 1977-04-19 | 1983-05-31 | Nazzaro Porro Marcella | Process for the treatment of acne |
GB2004746B (en) | 1977-10-03 | 1982-03-10 | Scherico Ltd | Stable hopical anaesthetic compositions |
JPS5639815Y2 (en) | 1977-11-25 | 1981-09-17 | ||
SE7713618L (en) | 1977-12-01 | 1979-06-02 | Astra Laekemedel Ab | LOCAL ANESTHETIC MIXTURE |
US4160827A (en) | 1978-02-06 | 1979-07-10 | The Upjohn Company | Metronidazole phosphate and salts |
US4229432A (en) | 1978-04-19 | 1980-10-21 | Bristol-Myers Company | Antiperspirant stick composition |
US4603812A (en) | 1978-06-27 | 1986-08-05 | The Dow Chemical Company | Foam-generating pump sprayer |
US4178373A (en) | 1978-08-21 | 1979-12-11 | William H. Rorer, Inc. | Coal tar gel composition |
US4214000A (en) | 1978-10-30 | 1980-07-22 | Johnson & Johnson | Zinc salt of all-trans-retinoic acid for the treatment of acne |
JPS5569682U (en) | 1978-11-08 | 1980-05-13 | ||
JPS5569682A (en) | 1978-11-20 | 1980-05-26 | Toyo Aerosol Kogyo Kk | Foam shrinkable composition |
US4213979A (en) | 1978-12-18 | 1980-07-22 | Plough, Inc. | Stable sprayable hydrocortisone product |
US4954487A (en) | 1979-01-08 | 1990-09-04 | The Procter & Gamble Company | Penetrating topical pharmaceutical compositions |
US4439441A (en) | 1979-01-11 | 1984-03-27 | Syntex (U.S.A.) Inc. | Contraceptive compositions and methods employing 1-substituted imidazole derivatives |
US4226344A (en) | 1979-02-06 | 1980-10-07 | Booth, Inc. | Constant flow valve actuator |
CH639913A5 (en) | 1979-03-16 | 1983-12-15 | Aerosol Service Ag | Container for receiving and delivering a liquid substance |
US4230701A (en) | 1979-03-21 | 1980-10-28 | Hoffmann-La Roche Inc. | Administration of biologically active vitamin D3 and vitamin D2 materials |
US4335120A (en) | 1979-03-21 | 1982-06-15 | Hoffmann-La Roche Inc. | Administration of biologically active vitamin D3 and vitamin D2 materials |
US4278206A (en) | 1979-04-13 | 1981-07-14 | Ae Development Corporation | Non-pressurized dispensing system |
US4241048A (en) | 1979-05-01 | 1980-12-23 | Bristol-Myers Company | Suspension composition of benzocaine |
JPS55153712A (en) | 1979-05-18 | 1980-11-29 | Kao Corp | Insulin pharmaceutical preparation and its production |
US4268499A (en) | 1979-06-07 | 1981-05-19 | Dow Corning Corporation | Antiperspirant emulsion compositions |
US4241149A (en) | 1979-07-20 | 1980-12-23 | Temple University | Canal clathrate complex solid electrolyte cell |
DE2931469A1 (en) | 1979-08-02 | 1981-02-26 | Bayer Ag | SURFACE SEALED MOLDED BODIES MADE OF CELLED POLYURETHANE ELASTOMERS AND METHOD FOR THE PRODUCTION THEREOF |
JPS5854931B2 (en) | 1979-09-04 | 1983-12-07 | トヨタ自動車株式会社 | broaching machine |
US4271149A (en) | 1979-09-21 | 1981-06-02 | West Agro-Chemical, Inc. | Germicidal iodine compositions with enhanced iodine stability |
US4299826A (en) | 1979-10-12 | 1981-11-10 | The Procter & Gamble Company | Anti-acne composition |
EP0032309A3 (en) | 1980-01-10 | 1981-08-05 | Imperial Chemical Industries Plc | Production of catalyst component, catalyst and use thereof |
US4309995A (en) | 1980-01-28 | 1982-01-12 | Sacco Susan M | Vaginal irrigation apparatus |
JPS56135416A (en) | 1980-03-27 | 1981-10-22 | Mitsubishi Chem Ind Ltd | Pharmaceutical preparation for skin |
SE8004580L (en) | 1980-06-19 | 1981-12-20 | Draco Ab | PHARMACEUTICAL PREPARATION |
US4338211A (en) | 1980-06-30 | 1982-07-06 | The Procter & Gamble Company | Liquid surfactant skin cleanser with lather boosters |
US4508705A (en) | 1980-07-02 | 1985-04-02 | Lever Brothers Company | Skin treatment composition |
US4323582A (en) | 1980-07-21 | 1982-04-06 | Siegel Norman H | Method of treating animals and humans for internal and external parasites |
JPS601113Y2 (en) | 1980-07-22 | 1985-01-12 | 三菱電機株式会社 | Round lighting equipment packaging |
JPS5914282B2 (en) | 1980-07-31 | 1984-04-04 | 株式会社神戸製鋼所 | Tube expansion drawing method |
US4329990A (en) | 1980-08-07 | 1982-05-18 | Sneider Vincent R | Expanding swab applicator |
US4325939A (en) | 1980-09-22 | 1982-04-20 | Richardson-Vicks Inc. | Zinc derivatives and their use in dental compositions |
US4305936A (en) | 1980-10-09 | 1981-12-15 | Dermik Laboratories | Topical corticosteroid formulations |
US4292250A (en) | 1980-11-17 | 1981-09-29 | Wisconsin Alumni Research Foundation | Vitamin D derivatives |
DE3176215D1 (en) | 1980-11-19 | 1987-07-02 | Procter & Gamble | Non-yellowing topical pharmaceutical composition |
JPS57501845A (en) | 1980-11-27 | 1982-10-14 | ||
DE3147726A1 (en) | 1980-12-03 | 1982-06-24 | Leo Pharmaceutical Products Ltd. A/S (Loevens kemiske Fabrik Produktionsaktieselskab), 2750 Ballerup | ANTIBIOTIC COMPLEXES, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL AGENTS THAT CONTAIN THESE COMPOUNDS |
US4352808A (en) | 1980-12-12 | 1982-10-05 | Schering Corporation | 3-Aralkyloxy-2,3-dihydro-2-(imidazolylmethyl)benzo(b)thiophenes and related derivatives, their use as antimicrobials and pharmaceutical formulations useful therefore |
US4323694A (en) | 1981-04-13 | 1982-04-06 | Finetex, Inc. | Benzoic acid esters |
US4522948A (en) | 1981-04-24 | 1985-06-11 | Syntex (U.S.A.) Inc. | Spermicidal substituted 1-(cycloalkyl)alkylimidazoles |
US4393066A (en) | 1981-06-05 | 1983-07-12 | Garrett David M | Method for treatment of herpetic lesions |
US4607101A (en) | 1981-08-27 | 1986-08-19 | Jaye-Boern Laboratories, Inc. | Method of treating acne vulgaris with a composition containing carbamide peroxide |
US4877805A (en) | 1985-07-26 | 1989-10-31 | Kligman Albert M | Methods for treatment of sundamaged human skin with retinoids |
US4469674A (en) | 1981-09-03 | 1984-09-04 | Richardson-Vicks Inc. | Stable oral compositions containing zinc and fluoride compounds |
US4440320A (en) | 1981-11-30 | 1984-04-03 | Wernicke Steven A | Foam dispensing apparatus |
LU83876A1 (en) | 1982-01-15 | 1983-09-02 | Oreal | COSMETIC COMPOSITION FOR TREATMENT OF KERATINIC FIBERS AND METHOD FOR TREATING THE SAME |
LU83949A1 (en) | 1982-02-16 | 1983-09-02 | Oreal | COMPOSITION FOR THE TREATMENT OF KERATINIC MATERIALS CONTAINING AT LEAST ONE CATIONIC POLYMER AND AT LEAST ONE ANIONIC LATEX |
US5087618A (en) | 1982-05-18 | 1992-02-11 | University Of Florida | Redox carriers for brain-specific drug delivery |
US4529605A (en) | 1983-01-12 | 1985-07-16 | Una E. Lynch | Bathing oil composition |
US4661340A (en) | 1983-06-06 | 1987-04-28 | Interkemia Vegyipari Gazdasagi Tarsasag | Quail egg based stabilized foam compositions for cosmetic purposes |
GB8315787D0 (en) | 1983-06-08 | 1983-07-13 | Briggs J H | Coolant spray |
JPS601113A (en) | 1983-06-20 | 1985-01-07 | Kao Corp | Hair-nourishing and hair-growing agent |
US4552872A (en) | 1983-06-21 | 1985-11-12 | The Procter & Gamble Company | Penetrating topical pharmaceutical compositions containing corticosteroids |
NL8302559A (en) | 1983-07-18 | 1985-02-18 | Philips Nv | ELECTROLYTIC CONDITIONER. |
GB8330969D0 (en) | 1983-11-21 | 1983-12-29 | Wellcome Found | Promoting healing |
US4612193A (en) | 1983-12-23 | 1986-09-16 | Del Laboratories, Inc. | Sty ointment and method of using the same |
GB8402748D0 (en) | 1984-02-02 | 1984-03-07 | Dunlop Ltd | Intravaginal device |
US4985459A (en) | 1984-02-08 | 1991-01-15 | Richardson-Vicks, Inc. | Analgesic and anti-inflammatory compositions comprising diphenhydramine and methods of using same |
US4912124A (en) | 1984-02-23 | 1990-03-27 | Ortho Pharmaceutical Corporation | Antifungal dermatological solution |
NZ207341A (en) | 1984-03-01 | 1988-02-29 | Harvey Alex Ind Ltd | Device containing chemical impregnants for insertion into a body cavity of an animal |
US4628063A (en) | 1984-03-08 | 1986-12-09 | Dana P. Brigham | Antiviral pharmaceutical preparations and methods for their use |
US4574052A (en) | 1984-05-31 | 1986-03-04 | Richardson-Vicks Inc. | Crackling aerosol foam |
GB8416638D0 (en) | 1984-06-29 | 1984-08-01 | Beecham Group Plc | Topical treatment and composition |
EP0172139B1 (en) | 1984-08-06 | 1988-09-14 | Ciba-Geigy Ag | Process for paper sizing with anionic hydrophobic sizing agents and cationic retention agents |
US4595526A (en) | 1984-09-28 | 1986-06-17 | Colgate-Palmolive Company | High foaming nonionic surfacant based liquid detergent |
SE443914B (en) | 1984-10-01 | 1986-03-17 | Torkel Ingemar Fischer | MEANS OF A SENSITIVITY TEST |
IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
CA1261276A (en) | 1984-11-09 | 1989-09-26 | Mark B. Grote | Shampoo compositions |
US4701320A (en) | 1984-11-29 | 1987-10-20 | Lederle (Japan), Ltd. | Composition stably containing minocycline for treating periodontal diseases |
US4627973A (en) | 1984-12-14 | 1986-12-09 | Charles Of The Ritz Group Ltd. | Skin mousse |
AU5078885A (en) | 1984-12-20 | 1986-06-26 | Warner-Lambert Company | Non-irritant detergent |
US4673569A (en) | 1985-02-12 | 1987-06-16 | Faberge Incorporated | Mousse hair composition |
DE3670569D1 (en) | 1985-03-01 | 1990-05-31 | Procter & Gamble | Mild cleaning foam. |
US5002680A (en) | 1985-03-01 | 1991-03-26 | The Procter & Gamble Company | Mild skin cleansing aerosol mousse with skin feel and moisturization benefits |
US4639367A (en) | 1985-03-18 | 1987-01-27 | Product Resources International, Inc. | Aerosol foam |
US4752465A (en) | 1985-09-20 | 1988-06-21 | Product Resources International, Inc. | Aerosol foam |
AU5549486A (en) | 1985-03-18 | 1986-10-13 | Product Resources International, Inc. | Exothermic stable foam compositions |
US5094853A (en) | 1985-04-26 | 1992-03-10 | S. C. Johnson & Son, Inc. | Method of preparing a water-soluble stable arthropodicidally-active foam matrix |
US4965063A (en) | 1985-05-24 | 1990-10-23 | Irene Casey | Cleaner and disinfectant with dye |
DE3521713A1 (en) | 1985-06-18 | 1986-12-18 | Henkel KGaA, 4000 Düsseldorf | OIL-IN-WATER EMULSIONS WITH IMPROVED VISCOSITY BEHAVIOR |
US4672078A (en) | 1985-07-03 | 1987-06-09 | Schering-Plough Corporation | Urea stabilized with a lactone in various pharmaceutical and cosmetic preparations |
GB8519426D0 (en) | 1985-08-01 | 1985-09-04 | Ici Plc | Composition for personal care products |
GB2179052B (en) | 1985-08-14 | 1989-03-30 | Procter & Gamble | Nonfoaming cleansing mousse with skin conditioning benefits |
US4806262A (en) | 1985-08-14 | 1989-02-21 | The Procter & Gamble Company | Nonlathering cleansing mousse with skin conditioning benefits |
AU6175586A (en) | 1985-09-11 | 1987-03-12 | Chesebrough-Pond's Inc. | Petroleum jelly, mild detergent anhydrous base compositions |
FR2591331A1 (en) | 1985-12-10 | 1987-06-12 | Drevet Jean Baptiste | Device for dispensing metered portions of a product contained in a pressurised receptacle |
US4837378A (en) | 1986-01-15 | 1989-06-06 | Curatek Pharmaceuticals, Inc. | Topical metronidazole formulations and therapeutic uses thereof |
GB8607570D0 (en) | 1986-03-26 | 1986-04-30 | Euro Celtique Sa | Vaginal pharmaceutical preparation |
JPS62241701A (en) | 1986-04-11 | 1987-10-22 | Maeda Kogyo Kk | Quick releasing device for hub for bicycle |
CA1291036C (en) | 1986-04-23 | 1991-10-22 | Edwin I. Stoltz | Nasal administration of drugs |
DE3614515A1 (en) | 1986-04-29 | 1987-11-05 | Pfeiffer Erich Gmbh & Co Kg | DISCHARGE DEVICE FOR MEDIA |
FR2598392B1 (en) | 1986-05-09 | 1988-08-26 | Oreal | PACKAGING FOR TWO PRESSURIZED CONTAINERS |
PH25150A (en) | 1986-06-05 | 1991-03-13 | Ciba Geigy Ag | Novel pharmaceutical preparation for topical application |
US4770634A (en) | 1986-06-11 | 1988-09-13 | Pellico Michael A | Method for treating teeth with foamable fluoride compositions |
JPS62299423A (en) | 1986-06-18 | 1987-12-26 | Mazda Motor Corp | Air-conditioner for vehicle |
US4837019A (en) | 1986-08-11 | 1989-06-06 | Charles Of The Ritz Group Ltd. | Skin treatment composition and method for treating burned skin |
US4906453A (en) | 1986-08-12 | 1990-03-06 | Jumpeer Nails, Inc. | Mousse product |
DE3628531A1 (en) | 1986-08-22 | 1988-02-25 | Merz & Co Gmbh & Co | FOAMABLE CREAMS |
AU597734B2 (en) | 1986-09-05 | 1990-06-07 | Upjohn Company, The | Sebum-dissolving nonaqueous minoxidil formulation |
WO1988001863A1 (en) | 1986-09-12 | 1988-03-24 | The Upjohn Company | Foams for delivery of minoxidil |
LU86585A1 (en) | 1986-09-15 | 1988-04-05 | Oreal | COMPOSITION IN THE FORM OF AN AEROSOL FOAM BASED ON A POLYMER DERIVED FROM QUATERNIZED CELLULOSE AND ANIONIC POLYMER |
JPH0778019B2 (en) | 1986-11-08 | 1995-08-23 | 久光製薬株式会社 | Foamed anti-inflammatory analgesic preparation |
EP0270316A3 (en) | 1986-12-04 | 1989-12-06 | Pfizer Inc. | Topical compositions comprising 1-substituted imidazoles and nsaids for treatment of acne |
US4822613A (en) | 1986-12-15 | 1989-04-18 | S. C. Johnson & Son, Inc. | Water-soluble foamable insecticidally-active compositions |
US4822614A (en) | 1986-12-19 | 1989-04-18 | S. C. Johnson & Son, Inc. | Bioactive film-forming composition for control of crawling insects and the like |
US5389677B1 (en) | 1986-12-23 | 1997-07-15 | Tristrata Inc | Method of treating wrinkles using glycalic acid |
US4863900A (en) | 1987-01-15 | 1989-09-05 | The Research Foundation Of State University Of New York | Method for reducing viral transmission with poly-L-histidine |
JPS63119420U (en) | 1987-01-30 | 1988-08-02 | ||
DE3704907A1 (en) | 1987-02-17 | 1988-08-25 | Bayer Ag | TOPICALLY APPLICABLE PREPARATIONS OF GYRASE INHIBITORS IN COMBINATION WITH CORTICOSTEROIDS |
US4828837A (en) | 1987-03-30 | 1989-05-09 | Liposome Technology, Inc. | Non-crystalline minoxidil composition, its production and application |
AU1388388A (en) | 1987-04-01 | 1988-10-06 | Dak-Laboratoriet A/S | Benzoic acid derivatives and use thereof |
LU86839A1 (en) | 1987-04-10 | 1988-12-13 | Oreal | DETERGENT AND FOAMING COSMETIC COMPOSITION, DELAYING RE-LUBRICATION OF HAIR |
WO1988008316A1 (en) | 1987-04-21 | 1988-11-03 | Chattan Nominees Pty. Ltd. | Vaginal douche |
FR2615173B1 (en) | 1987-05-13 | 1989-08-18 | Valois | DOSING VALVE FOR LIQUID LOADED WITH A LIQUID OR LIQUEFIED GAS PROPELLER, FOR USE IN THE REVERSE POSITION |
US4867967A (en) | 1987-06-04 | 1989-09-19 | Crutcher Wilbert L | Method for the treatment of pseudofolliculitis barbae |
US4780309A (en) | 1987-06-16 | 1988-10-25 | Warner-Lambert Company | Edible aerosol foam compositions and method of preparing same |
US4849117A (en) | 1987-06-17 | 1989-07-18 | Sanitek Products, Inc. | Concentrated composition for forming an aqueous foam |
US4885282A (en) | 1987-07-02 | 1989-12-05 | Thornfeldt Carl R | Treatment of hyperhidrosis, ichthyosis and wrinkling |
US4898246A (en) | 1987-07-06 | 1990-02-06 | Total Walther Feuerschutz Gmbh | Quick release valve for sprinkler head |
US5196405A (en) | 1987-07-08 | 1993-03-23 | Norman H. Oskman | Compositions and methods of treating hemorrhoids and wounds |
US4847068A (en) | 1987-08-06 | 1989-07-11 | Johnson & Johnson Consumer Products, Inc. | Skin care compositions |
US4913893A (en) | 1987-08-28 | 1990-04-03 | Clairol Incorporated | Aerosol hair setting composition containing an alginate |
CA1273576A (en) | 1987-09-16 | 1990-09-04 | Patrick A. Beauchamp | Topical treatment for diseased skin disorders |
DE309353T1 (en) | 1987-09-23 | 1991-02-07 | L'oreal, Paris, Fr | SKIN TREATMENT AGENT AS AEROSOL FOAM CONTAINING VASILINE. |
US4981677A (en) | 1987-09-23 | 1991-01-01 | L'oreal | Petrolatum-containing aerosol foam concentrate |
US4784842A (en) | 1987-09-25 | 1988-11-15 | Jean London | Therapeutic composition for treatment of cuts, burns and abrasions |
US4772427A (en) | 1987-12-01 | 1988-09-20 | Colgate-Palmolive Co. | Post-foaming gel shower product |
US5143717A (en) | 1987-12-30 | 1992-09-01 | Code Blue Medical Corporation | Burn foam and delivery system |
EP0326196B1 (en) | 1988-01-14 | 1992-03-25 | Akzo N.V. | Aqueous pharmaceutical preparation |
US5536743A (en) | 1988-01-15 | 1996-07-16 | Curatek Pharmaceuticals Limited Partnership | Intravaginal treatment of vaginal infections with buffered metronidazole compositions |
JP2643217B2 (en) | 1988-01-22 | 1997-08-20 | エーザイ株式会社 | Aqueous liquid of fat-soluble substance |
US5719197A (en) | 1988-03-04 | 1998-02-17 | Noven Pharmaceuticals, Inc. | Compositions and methods for topical administration of pharmaceutically active agents |
US4849211A (en) | 1988-03-16 | 1989-07-18 | Schrauzer Gerhard N | Product and method for the treatment of acne and other skin disorders |
US4897262A (en) | 1988-03-22 | 1990-01-30 | Playtex Jhirmack, Inc. | Non-aerosol hair spray composition |
DE3811081A1 (en) | 1988-03-30 | 1989-10-12 | Schering Ag | USE OF TOPIC APPLICABLE PREPARATIONS FOR THE TREATMENT OF AGING SKIN |
LU87187A1 (en) | 1988-03-31 | 1989-10-26 | Oreal | COMBINATION OF PYRIMIDINE DERIVATIVES AND SALICYLIC ACID DERIVATIVES FOR INDUCING AND STIMULATING HAIR GROWTH AND REDUCING HAIR LOSS |
US4992478A (en) | 1988-04-04 | 1991-02-12 | Warner-Lambert Company | Antiinflammatory skin moisturizing composition and method of preparing same |
US4873078A (en) | 1988-04-22 | 1989-10-10 | Plough, Inc. | High-gloss, high-shine lipstick |
GB8811409D0 (en) | 1988-05-13 | 1988-06-15 | Unilever Plc | Cosmetic composition |
US5378730A (en) | 1988-06-09 | 1995-01-03 | Alza Corporation | Permeation enhancer comprising ethanol and monoglycerides |
GB8813766D0 (en) | 1988-06-10 | 1988-07-13 | Efamol Holdings | Essential fatty acid compositions |
US4827378A (en) | 1988-06-15 | 1989-05-02 | Rockwell International Corporation | Jack coaxial connector EMI shielding apparatus |
US5217707A (en) | 1988-06-16 | 1993-06-08 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt. | Pharmaceutical composition and process for the preparation thereof |
EP0349875A3 (en) | 1988-07-07 | 1991-09-25 | General Electric Company | Paintable elestomeric compositions |
US4902281A (en) | 1988-08-16 | 1990-02-20 | Corus Medical Corporation | Fibrinogen dispensing kit |
US4950420A (en) | 1988-08-31 | 1990-08-21 | Nalco Chemical Company | Antifoam/defoamer composition |
US4855294A (en) | 1988-09-06 | 1989-08-08 | Theratech, Inc. | Method for reducing skin irritation associated with drug/penetration enhancer compositions |
GB8821129D0 (en) | 1988-09-09 | 1988-10-12 | Unilever Plc | Cosmetic composition |
JPH02191223A (en) | 1988-10-04 | 1990-07-27 | Otsuka Pharmaceut Co Ltd | Iron-supplying preparation |
US5135915A (en) | 1988-10-14 | 1992-08-04 | Genentech, Inc. | Method for the treatment of grafts prior to transplantation using TGF-.beta. |
US5186857A (en) | 1988-11-14 | 1993-02-16 | Imaginative Research Associates, Inc. | Self-foaming oil compositions and process for making and using same |
GB8828013D0 (en) | 1988-12-01 | 1989-01-05 | Unilever Plc | Topical composition |
US4970067A (en) | 1988-12-12 | 1990-11-13 | Helene Curtis, Inc. | Method and composition to condition hair and impart semi-permanent hair set retention properties |
US5262407A (en) | 1988-12-16 | 1993-11-16 | L'oreal | Use of salicylic derivatives for the treatment of skin aging |
FR2640942A1 (en) | 1988-12-23 | 1990-06-29 | Suchard Sa Jacobs | Container of the aerosol type for delivering, in the form of a foam, metered quantities of product, particularly of food product |
DE68913693T3 (en) | 1988-12-27 | 2004-01-22 | Osaka Shipbuilding Co., Ltd. | Aerosol composition. |
JP2960445B2 (en) | 1988-12-28 | 1999-10-06 | 株式会社大阪造船所 | Aerosol composition |
FR2641185B1 (en) | 1988-12-29 | 1991-04-05 | Oreal | SHAVING COMPOSITION FOR THE SKIN BASED ON ACYLOXYALKYL FUNCTIONAL POLYORGANOSILOXANES AND METHOD FOR IMPLEMENTING SAME |
JP2741230B2 (en) | 1989-01-11 | 1998-04-15 | 株式会社コーセー | Foam anhydrous cosmetics |
LU87449A1 (en) | 1989-02-09 | 1990-09-19 | Oreal | PROCESS FOR THE MANUFACTURE OF FOAMS FOR USE IN THE COSMETIC AND PHARMACEUTICAL AREAS AND FOAMS OBTAINED BY THIS PROCESS |
US4919934A (en) | 1989-03-02 | 1990-04-24 | Richardson-Vicks Inc. | Cosmetic sticks |
US4996193A (en) | 1989-03-03 | 1991-02-26 | The Regents Of The University Of California | Combined topical and systemic method of administration of cyclosporine |
US5019375A (en) | 1989-03-14 | 1991-05-28 | The Procter & Gamble Company | Low residue antiperspirant creams |
ES2103737T3 (en) | 1989-03-17 | 1997-10-01 | Taisho Pharmaceutical Co Ltd | PREPARATION OF AEROSOL FOR EXTERNAL USE. |
US5221696A (en) | 1989-03-29 | 1993-06-22 | Alcon Laboratories, Inc. | Use of monoacyl phosphoglycerides to enhance the corneal penetration of ophthalmic drugs |
EP0391124B1 (en) | 1989-04-05 | 1995-06-21 | Kao Corporation | Cosmetic composition of double emulsion type |
US5071648A (en) | 1989-04-06 | 1991-12-10 | Merocel Corporation | Polymeric broad-spectrum antimicrobial materials |
US5204093A (en) | 1989-04-06 | 1993-04-20 | Victor Steven A | Shaving cream composition for the treatment of acne vulgaris and pseudofolliculitis barbae and method of producing and using same |
US5618798A (en) | 1989-04-20 | 1997-04-08 | Bar-Shalom; Daniel | Use of sucralfate to treat baldness |
GB8909559D0 (en) | 1989-04-26 | 1989-06-14 | Smith Kline French Lab | Pharmaceutical compositions |
US5221534A (en) | 1989-04-26 | 1993-06-22 | Pennzoil Products Company | Health and beauty aid compositions |
US4874794A (en) | 1989-04-28 | 1989-10-17 | Lidak Biopharmaceuticals | Inflammatory disease treatment |
US5322683A (en) | 1989-05-01 | 1994-06-21 | Leonard Mackles | Anhydrous aerosol foam |
US5002540A (en) | 1989-05-22 | 1991-03-26 | Warren Kirschbaum | Intravaginal device and method for delivering a medicament |
GB8911853D0 (en) | 1989-05-23 | 1989-07-12 | Ici Plc | Co2 blown integral skin foams |
CA1337279C (en) | 1989-06-06 | 1995-10-10 | Robert J. Borgman | Intravaginal treatment of vaginal infections with buffered metronidazole compositions |
US5208031A (en) | 1989-06-06 | 1993-05-04 | Kelly Patrick D | Sexual lubricants containing zinc as an anti-viral agent |
JPH0310636A (en) | 1989-06-09 | 1991-01-18 | Matsushita Electric Works Ltd | Vegetable storage chamber under floor |
US5122519A (en) | 1989-06-27 | 1992-06-16 | American Cyanamid Company | Stable, cosmetically acceptable topical gel formulation and method of treatment for acne |
MX21452A (en) | 1989-07-07 | 1994-01-31 | Ciba Geigy Ag | PHARMACEUTICAL PREPARATIONS THAT ARE TOPICALLY ADMINISTERED. |
JPH0350289A (en) | 1989-07-17 | 1991-03-04 | Shiseido Co Ltd | Non-emulsion type foam aerosol composition |
US5560859A (en) | 1989-07-26 | 1996-10-01 | Pfizer Inc. | Post foaming gel shaving composition |
US4981367A (en) | 1989-07-28 | 1991-01-01 | Stranco, Inc. | Portable mixing apparatus |
ATE124860T1 (en) | 1989-07-28 | 1995-07-15 | Hisamitsu Pharmaceutical Co | FOAM AEROSOL COMPOSITION. |
JPH0383914A (en) | 1989-08-18 | 1991-04-09 | W R Grace & Co | Drug carrier |
US5219877A (en) | 1989-09-25 | 1993-06-15 | Bristol-Myers Squibb Company | Lauryl alcohol as skin penetration enhancer for topical imidazole agents |
IL95952A0 (en) | 1989-10-19 | 1991-07-18 | Sterling Drug Inc | Aerosol composition for topical medicament |
US5439670A (en) | 1989-11-28 | 1995-08-08 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
US5508033A (en) | 1989-12-06 | 1996-04-16 | Societe D'engrais Composes Mineraux Et Amendments | Utilization of algae extract for the preparation of pharmaceutical, cosmetic, food or agricultural compositions |
US5295984A (en) | 1989-12-07 | 1994-03-22 | Ultrafem, Inc. | Vaginal discharge collection device and intravaginal drug delivery system |
DE69034134T2 (en) | 1989-12-07 | 2004-09-09 | Instead, Inc., Missoula | METHOD FOR COLLECTING VAGINAL EMISSIONS |
AU6974191A (en) | 1989-12-20 | 1991-07-18 | Schering Corporation | Stable cream and lotion bases for lipophilic drug compositions |
US4966779A (en) | 1989-12-21 | 1990-10-30 | Basf Corporation | Stable, water miscible emulsion comprising a fat-soluble vitamin |
US5733572A (en) | 1989-12-22 | 1998-03-31 | Imarx Pharmaceutical Corp. | Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles |
US4963351A (en) | 1989-12-26 | 1990-10-16 | Bhn Associates | Shaving aid |
US5100917A (en) | 1989-12-29 | 1992-03-31 | Merrell Dow Pharmaceuticals Inc. | Novel a-nor-steroid-3-carboxylic acid derivatives |
US5104645A (en) | 1990-02-02 | 1992-04-14 | The Proctor & Gamble Company | Antidandruff shampoo compositions |
SE9000485D0 (en) | 1990-02-09 | 1990-02-09 | Pharmacia Ab | FOAMABLE COMPOSITION FOR PHARMACEUTICAL USE, USE THEREOF AND METHOD OF TREATMENT |
US5164367A (en) | 1990-03-26 | 1992-11-17 | Procyte Corporation | Method of using copper(ii) containing compounds to accelerate wound healing |
US5130121A (en) | 1990-04-17 | 1992-07-14 | Isp Investments Inc. | Skin care compositions containing discrete microdroplets of an oil in water stabilized by in situ polymerization of water-soluble vinyl monomer |
US5007556A (en) | 1990-04-18 | 1991-04-16 | Block Drug Company, Inc. | Metering dispenser |
US5156765A (en) | 1990-05-15 | 1992-10-20 | Fox Valley Systems, Inc. | Aerosol foam marking compositions |
US5112359A (en) | 1990-06-04 | 1992-05-12 | Clairol, Inc. | Hair colorants |
JP3649341B2 (en) | 1990-06-15 | 2005-05-18 | 株式会社資生堂 | COMPOSITE AND COMPOSITE COMPOSITION, EMULSION COMPOSITION, AND EMULSION COMPOSITION |
JPH0451958A (en) | 1990-06-18 | 1992-02-20 | Mitsubishi Materials Corp | Treating agent for circulation type toilet filth |
US5034220A (en) | 1990-06-20 | 1991-07-23 | Gaf Chemicals Corporation | Non-aerosol shaving gel |
US5336692A (en) | 1990-06-28 | 1994-08-09 | Medicis Pharmaceutical Corporation | Ointment base and method of use |
IT1243379B (en) | 1990-07-27 | 1994-06-10 | Giuliani Spa | PHARMACEUTICAL COMPOSITION SUITABLE FOR RECTAL ADMINISTRATION OF ACTIVE PRINCIPLES WHICH EXPLICATE A MEDICATION ACTION AT THE LEVEL OF THE COLON, PREVALENTLY TOPICAL |
US5108556A (en) | 1990-09-14 | 1992-04-28 | Minnesota Mining And Manufacturing Company | Process for preparing tertiary perfluoroamines |
US5091111A (en) | 1990-09-19 | 1992-02-25 | S. C. Johnson & Son, Inc. | Aqueous emulsion and aersol delivery system using same |
US5114718A (en) | 1990-09-20 | 1992-05-19 | The Procter & Gamble Company | Sustained release compositions for treating periodontol disease |
GB9021546D0 (en) | 1990-10-04 | 1990-11-21 | Beecham Group Plc | Novel composition |
FR2668927B1 (en) | 1990-11-09 | 1993-01-08 | Oreal | COSMETIC ANHYDROUS COMPOSITION IN AEROSOL FORM FOR THE FORMATION OF A FOAM. |
DE9016291U1 (en) | 1990-11-30 | 1991-03-28 | Kali-Chemie Pharma Gmbh, 3000 Hannover, De | |
US5073371A (en) | 1990-11-30 | 1991-12-17 | Richardson-Vicks, Inc. | Leave-on facial emulsion compositions |
WO1992011839A1 (en) | 1991-01-08 | 1992-07-23 | Leonard Mackles | Anhydrous aerosol |
AU1411992A (en) | 1991-01-15 | 1992-08-27 | Robert A Bok | A composition containing a tetracycline and use for inhibiting angiogenesis |
US5227163A (en) | 1991-01-18 | 1993-07-13 | Clilco, Ltd. | Lice-repellant compositions |
DE4102506C2 (en) | 1991-01-29 | 1999-11-25 | Pfeiffer Erich Gmbh & Co Kg | Discharge device for media |
CA2101947A1 (en) | 1991-02-05 | 1992-08-06 | Jurgen Buil | Fire extinguishing and protection agent |
US5948682A (en) | 1991-02-22 | 1999-09-07 | Sembiosys Genetics Inc. | Preparation of heterologous proteins on oil bodies |
US5650554A (en) | 1991-02-22 | 1997-07-22 | Sembiosys Genetics Inc. | Oil-body proteins as carriers of high-value peptides in plants |
US6753167B2 (en) | 1991-02-22 | 2004-06-22 | Sembiosys Genetics Inc. | Preparation of heterologous proteins on oil bodies |
US5658956A (en) | 1991-03-01 | 1997-08-19 | Warner-Lambert Company | Bioadhesive-wound healing compositions and methods for preparing and using same |
US5648380A (en) | 1991-03-01 | 1997-07-15 | Warner-Lambert Company | Anti-inflammatory wound healing compositions and methods for preparing and using same |
US5663208A (en) | 1991-03-01 | 1997-09-02 | Warner-Lambert Company | Antifungal wound healing compositions and methods for preparing and using same |
IT1247138B (en) | 1991-03-06 | 1994-12-12 | Dompe Farmaceutici Spa | HYDROPHILE PHARMACEUTICAL COMPOSITION CONTAINING KETOPROFENE LYSINE SALT FOR TOPICAL USE. |
JPH04282311A (en) | 1991-03-08 | 1992-10-07 | Koike Kagaku Kk | Aerosol-type foamable wound-disinfectant |
US5279819A (en) | 1991-03-18 | 1994-01-18 | The Gillette Company | Shaving compositions |
WO1992016236A1 (en) | 1991-03-19 | 1992-10-01 | Rajadhyaksha Vithal J | Compositions and method comprising aminoalcohol derivatives as membrane penetration enhancers |
US5389676A (en) | 1991-03-22 | 1995-02-14 | E. B. Michaels Research Associates, Inc. | Viscous surfactant emulsion compositions |
AU658608B2 (en) | 1991-03-25 | 1995-04-27 | Astellas Pharma Europe B.V. | Topical preparation containing a suspension of solid lipid particles |
US5167950A (en) | 1991-03-28 | 1992-12-01 | S. C. Johnson & Son | High alcohol content aerosol antimicrobial mousse |
DE4110973A1 (en) | 1991-04-05 | 1992-10-08 | Haarmann & Reimer Gmbh | MEDIUM WITH A PHYSIOLOGICAL COOLING EFFECT AND EFFECTIVE COMPOUNDS SUITABLE FOR THIS MEDIUM |
JP3100416B2 (en) | 1991-04-11 | 2000-10-16 | オカモト株式会社 | Moose-like lubricant |
HU209605B (en) | 1991-04-15 | 1994-09-28 | Chinoin Gyogyszer Es Vegyeszet | Process for production of wather-free transdermal preparation |
IT1247529B (en) | 1991-04-24 | 1994-12-17 | Poli Ind Chimica Spa | PHARMACEUTICAL COMPOSITIONS IN FOAM FORM FOR INTRAVAGINAL, SKIN AND ORAL ADMINISTRATION |
US5204090A (en) | 1991-05-30 | 1993-04-20 | Bristol Myers Squibb | Waterproof high-SPF sunscreen compositions |
US5164357A (en) | 1991-06-05 | 1992-11-17 | Appleton Papers Inc. | Thermally-responsive record material |
FR2677544B1 (en) | 1991-06-14 | 1993-09-24 | Oreal | COSMETIC COMPOSITION CONTAINING A MIXTURE OF NANOPIGMENTS OF METAL OXIDES AND MELANIC PIGMENTS. |
US5221530A (en) | 1991-06-24 | 1993-06-22 | Helene Curtis, Inc. | Mild conditioning shampoo with a high foam level containing an anionic surfactant-cationic acrylate/acrylamide copolymer conditioning agent |
DE4210165A1 (en) | 1991-07-30 | 1993-02-04 | Schering Ag | TRANSDERMAL THERAPEUTIC SYSTEMS |
DE4127630A1 (en) | 1991-08-21 | 1993-02-25 | Bruno Jesswein | TWO-COMPONENT PRESSURE CAN, IN PARTICULAR FOR 2K FOAM |
GB9118028D0 (en) | 1991-08-21 | 1991-10-09 | Secr Defence Brit | Improved transdrmal formulations |
JP2969398B2 (en) | 1991-09-12 | 1999-11-02 | 花王株式会社 | Anhydrous foam cleaning agent |
US5643600A (en) | 1991-09-17 | 1997-07-01 | Micro-Pak, Inc. | Lipid vesicles containing avocado oil unsaponifiables |
US5589515A (en) | 1991-09-27 | 1996-12-31 | Nof Corporation | Cosmetic composition and an emulsion composition |
GB2260079B (en) | 1991-10-01 | 1995-08-09 | American Cyanamid Co | Pharmaceutical composition containing felbinac |
US5230897A (en) | 1991-10-31 | 1993-07-27 | G. D. Searle & Co. | Transdermal pentamidine |
US5236707A (en) | 1991-11-08 | 1993-08-17 | Dallas Biotherapeutics, Inc. | Stabilization of human interferon |
JPH07501077A (en) | 1991-11-22 | 1995-02-02 | リチャードソン、ビックス、インコーポレーテッド | Combination personal cleansing and moisturizing composition |
DE4140474C2 (en) | 1991-12-09 | 1995-07-13 | Schuelke & Mayr Gmbh | Skincare additive |
US5294365A (en) | 1991-12-12 | 1994-03-15 | Basf Corporation | Hydroxypolyethers as low-foam surfactants |
IT1253711B (en) | 1991-12-17 | 1995-08-23 | Alfa Wassermann Spa | VAGINAL PHARMACEUTICAL FORMULATIONS CONTAINING RIFAXIMIN AND THEIR USE IN THE TREATMENT OF VAGINAL INFECTIONS |
US5252246A (en) | 1992-01-10 | 1993-10-12 | Allergan, Inc. | Nonirritating nonionic surfactant compositions |
EP0552612A3 (en) | 1992-01-22 | 1993-10-20 | Hoffmann La Roche | Methods for determining and isolating compounds which bind directly to nucleosolic proteins |
JP3146052B2 (en) | 1992-01-31 | 2001-03-12 | プレスコ株式会社 | Aerosol massage agent |
US5318774A (en) | 1992-02-28 | 1994-06-07 | Richardson-Vicks Inc. | Composition and method for imparting an artificial tan to human skin |
AU678154B2 (en) | 1992-04-02 | 1997-05-22 | Sembiosys Genetics Inc. | Oil-body protein cis-elements as regulatory signals |
US5344051A (en) | 1992-04-27 | 1994-09-06 | Insta-Foam Products, Inc. | Two-component foam dispensing apparatus |
ZA932947B (en) | 1992-04-28 | 1993-10-27 | Schering Plough Healthcare | Applicator for semisolid medications |
US5409706A (en) | 1992-05-04 | 1995-04-25 | Imaginative Research Associates, Inc. | Anhydrous foaming composition containing low concentrations of detergents and high levels of glycerin and emollients such as oils and esters |
US5254334A (en) | 1992-05-04 | 1993-10-19 | Imaginative Research Associates, Inc. | Anhydrous foaming composition containing low concentrations of detergents and high levels of glycerin amd emollients such as oils and esters |
ZA933133B (en) | 1992-05-15 | 1994-10-05 | Akzo Nv | Application for introducing a cream-type substance into a woman's vagina |
AU4116993A (en) | 1992-05-18 | 1993-12-13 | Procter & Gamble Company, The | Coolant compositions |
US5389305A (en) | 1992-06-03 | 1995-02-14 | Colgate Palmolive Co. | High foaming nonionic surfactant base liquid detergent |
DK0644746T3 (en) | 1992-06-11 | 1999-12-20 | Theratech Inc | Use of glycerine to moderate transdermal drug delivery |
US5346135A (en) | 1992-06-16 | 1994-09-13 | Vincent Edward C | Spraying apparatus for blending liquids in a gaseous spray system |
US5300286A (en) | 1992-07-14 | 1994-04-05 | Dow Corning Corporation | Silicone emulsion for personal care application |
ES2101330T3 (en) | 1992-07-28 | 1997-07-01 | Procter & Gamble | PHARMACEUTICAL COMPOSITION FOR TOPICAL USE CONTAINING A RETICULATED CATIONIC POLYMER AND AN ALCOXYLATED ETHER. |
FI933979A0 (en) | 1992-09-10 | 1993-09-10 | Mcneil Ppc Inc | BIOERODERBAR ANORDNING FOER DOSERING AV AKTIVA INGREDIENSER |
RU2113216C1 (en) | 1992-09-14 | 1998-06-20 | П.Смит Уолтер | Cosmetic composition (versions) |
JPH06100414A (en) | 1992-09-18 | 1994-04-12 | Osaka Aerosol Ind Corp | Composition for aerosol |
US6096756A (en) | 1992-09-21 | 2000-08-01 | Albert Einstein College Of Medicine Of Yeshiva University | Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other bimodally-acting opioid agonists |
US5413775A (en) | 1992-09-29 | 1995-05-09 | Amerchol Corporation | Hairsprays and acrylic polymer compositions for use therein |
IT1255895B (en) | 1992-10-20 | 1995-11-17 | Laura Chiodini | PHARMACEUTICAL COMPOSITIONS CONTAINING A CALCITONIN |
EP0665733B1 (en) | 1992-10-21 | 2003-05-07 | Gynetech Laboratories, Inc. | Vaginal sponge delivery system |
DE59308338D1 (en) | 1992-10-31 | 1998-05-07 | Goldschmidt Ag Th | Cosmetic or pharmaceutical preparations |
DE4238860A1 (en) | 1992-11-19 | 1994-05-26 | Medicon Gmbh | Skin protection products for the protection of human skin |
US5308643A (en) | 1992-11-30 | 1994-05-03 | Osipow Lloyd I | Self-lather generating shaving compositions |
JP3328344B2 (en) | 1992-12-22 | 2002-09-24 | タイホー工業株式会社 | Method of controlling foaming state retention time of foaming type cleaning polishes |
JPH06263630A (en) | 1993-03-10 | 1994-09-20 | Lion Corp | Vitamin as-solubilizing eye drop |
DE4309900C1 (en) | 1993-03-26 | 1994-06-30 | Goldschmidt Ag Th | Process for the preparation of amphoteric surfactants |
JPH06279228A (en) | 1993-03-30 | 1994-10-04 | Kao Corp | Foaming composition |
US5326557A (en) | 1993-04-06 | 1994-07-05 | Dow Corning Corporation | Moisturizing compositions containing organosilicon compounds |
US5807571A (en) | 1993-05-06 | 1998-09-15 | Lts Lohmann Therapie-Systeme Gmbh | Transdermal therapeutic systems for administering indole serotonin agonists |
US5576016A (en) | 1993-05-18 | 1996-11-19 | Pharmos Corporation | Solid fat nanoemulsions as drug delivery vehicles |
DE69430917T2 (en) | 1993-05-19 | 2003-03-20 | Hisamitsu Pharmaceutical Co | 3-L-MENTHOXY-PROPANE-1, 2-DIOL AS SOLUTION AND EXTERNAL PREPARATION THAT CONTAINS THEM |
CA2161431A1 (en) | 1993-05-21 | 1994-12-08 | Barry A. Salka | Mild shampoo composition |
JP3161869B2 (en) | 1993-05-24 | 2001-04-25 | 株式会社ダイゾー | Water-in-oil aerosol composition and process for producing the same |
US5635469A (en) | 1993-06-10 | 1997-06-03 | The Procter & Gamble Company | Foaming cleansing products |
US5447725A (en) | 1993-06-11 | 1995-09-05 | The Procter & Gamble Company | Methods for aiding periodontal tissue regeneration |
US5384308A (en) | 1993-06-14 | 1995-01-24 | Henkin; R. I. | Composition and method for enhancing wound healing |
US5744155A (en) | 1993-08-13 | 1998-04-28 | Friedman; Doron | Bioadhesive emulsion preparations for enhanced drug delivery |
US5398846A (en) | 1993-08-20 | 1995-03-21 | S. C. Johnson & Son, Inc. | Assembly for simultaneous dispensing of multiple fluids |
US6596260B1 (en) | 1993-08-27 | 2003-07-22 | Novartis Corporation | Aerosol container and a method for storage and administration of a predetermined amount of a pharmaceutically active aerosol |
FR2709666B1 (en) | 1993-09-07 | 1995-10-13 | Oreal | Cosmetic or dermatological composition consisting of an oil-in-water emulsion based on oily globules provided with a lamellar liquid crystal coating. |
JP2978043B2 (en) | 1993-09-16 | 1999-11-15 | 高砂香料工業株式会社 | (2S) -3-{(1R, 2S, 5R)-[5-methyl-2- (1-methylethyl) cyclohexyl] oxy} -1,2-propanediol, its production method and use |
US5766632A (en) | 1993-10-01 | 1998-06-16 | Legere Pharmaceuticals, Ltd. | Method of using lectins for contraception |
FR2710854B1 (en) | 1993-10-08 | 1995-12-01 | Oreal | Oil-in-water emulsion usable for obtaining a cream. |
US5578315A (en) | 1993-12-01 | 1996-11-26 | Rutgers, The State University Of New Jersey | Mucosal adhesive device for long-acting delivery of pharmaceutical combinations in oral cavity |
FR2713486B1 (en) | 1993-12-14 | 1996-02-09 | Scophysa | New compositions for foams, in particular rectal foams, and foams thus obtained. |
DE69426727D1 (en) | 1993-12-23 | 2001-03-29 | Procter & Gamble | ANTIMICROBIAL COMPOSITIONS FOR WIPES |
US5527822A (en) | 1993-12-29 | 1996-06-18 | Forest Laboratories, Inc. | Method of treatment of traumatic brain injury |
DE9422052U1 (en) | 1994-01-04 | 1997-10-30 | Wuerth Adolf Gmbh & Co Kg | Filling device for filling a refillable dispensing container and refillable dispensing container |
JP3530564B2 (en) | 1994-02-03 | 2004-05-24 | 株式会社ノエビア | Aerosol foam cosmetics |
DE4405127A1 (en) | 1994-02-18 | 1995-08-31 | Henkel Kgaa | Hair treatment products |
US5514367A (en) | 1994-02-28 | 1996-05-07 | Estee Lauder, Inc. | Skin tanning compositions and methods for their preparation and use |
US5925669A (en) | 1994-03-22 | 1999-07-20 | Molecular/Structural Bio Technologies, Inc. | Carrier compositions for anti-neoplastic drugs |
US5658749A (en) | 1994-04-05 | 1997-08-19 | Corning Clinical Laboratories, Inc. | Method for processing mycobacteria |
IL109230A (en) | 1994-04-05 | 1998-08-16 | Agis Ind 1983 Ltd | Anti-fungal composition containing bifonazole and fluocinonide |
US5429815A (en) | 1994-04-11 | 1995-07-04 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Stable single-phase self-foaming cleanser |
FR2719467B1 (en) | 1994-05-05 | 1996-05-31 | Oreal | Use of flavonoids to preserve and / or strengthen the mechanical properties of the hair and method of protecting hair using these compounds. |
ES2079320B1 (en) | 1994-05-17 | 1996-10-16 | Cusi Lab | OPHTHALMIC DISSOLUTION BASED ON A DICLOFENACO AND TOBRAMYCIN AND ITS APPLICATIONS. |
US5902574A (en) | 1994-05-23 | 1999-05-11 | The Gillette Company | Shaving preparation for improved shaving comfort |
US5545401A (en) | 1994-06-02 | 1996-08-13 | Shanbrom; Edward | Antiviral, spermicidal vaginal gel and foam containing low molecular weight povidone-iodine |
FR2720635B1 (en) | 1994-06-03 | 1996-07-26 | Oreal | Sunscreen cosmetic compositions and uses. |
US6221381B1 (en) | 1994-06-28 | 2001-04-24 | The University Of British Columbia | Enhancing milk production by adding to feed a nonionic surfactant coated on a carrier |
MA23592A1 (en) | 1994-06-30 | 1995-12-31 | Procter & Gamble | COMPOSITIONS FOR BODY CARE CONTAINING THERMOPLASTIC ELASTOMERIC GRAFT COPOLYMERS |
US5679324A (en) | 1994-07-08 | 1997-10-21 | The Procter & Gamble Co. | Aerosol foamable fragrance composition |
FR2722431B1 (en) | 1994-07-12 | 1996-09-13 | Lir France Sa | DOUBLE DISPENSER FOR FLUID PRODUCTS |
US5869529A (en) | 1994-07-20 | 1999-02-09 | Agis Industries (1983) Ltd. | Topical preparation for the prevention and treatment of lesions and sores associated with a herpes virus |
JP3173330B2 (en) | 1994-07-20 | 2001-06-04 | トヨタ自動車株式会社 | Slip control device for vehicle lock-up clutch |
US5444092A (en) | 1994-07-20 | 1995-08-22 | Collins; Jerry | Method and composition for treating psoriasis |
US5512555A (en) | 1994-07-21 | 1996-04-30 | Merck & Co., Inc. | Method of treating sweat-related conditions using finasteride, epristeride and a cholestan-3-one |
GB9414699D0 (en) | 1994-07-21 | 1994-09-07 | Slagel David | Aqueous foamable composition |
JP3241542B2 (en) | 1994-07-29 | 2001-12-25 | 高砂香料工業株式会社 | Method for purifying (-)-n-isopulegol and citrus-based fragrance composition containing (-)-n-isopulegol obtained by the method |
JPH0840899A (en) | 1994-07-29 | 1996-02-13 | Tokyo Tanabe Co Ltd | Aerosol of oxyconazone nitrate |
DE4428096A1 (en) | 1994-08-09 | 1996-02-15 | Wella Ag | Two-chamber container |
US5656586A (en) | 1994-08-19 | 1997-08-12 | Rhone-Poulenc Inc. | Amphoteric surfactants having multiple hydrophobic and hydrophilic groups |
US5547989A (en) | 1994-08-19 | 1996-08-20 | Schering-Plough Healthcare Products, Inc. | Compositions for treating corns and calluses |
JPH10505061A (en) | 1994-08-26 | 1998-05-19 | ザ、プロクター、エンド、ギャンブル、カンパニー | Personal cleansing composition |
JP3558393B2 (en) | 1994-08-29 | 2004-08-25 | 株式会社ダイゾー | Foamable aerosol composition |
TW460296B (en) | 1994-09-01 | 2001-10-21 | Janssen Pharmaceutica Nv | Topical ketoconazole emulsion compositions without sodium sulfite |
US5976555A (en) | 1994-09-07 | 1999-11-02 | Johnson & Johnson Consumer Products, Inc. | Topical oil-in-water emulsions containing retinoids |
JP3604177B2 (en) | 1994-09-14 | 2004-12-22 | 日東電工株式会社 | Transdermal formulation |
US5500211A (en) | 1994-09-22 | 1996-03-19 | The Gillette Company | Soap-free self-foaming shave gel composition |
US5905092A (en) | 1994-09-27 | 1999-05-18 | Virotex Corporation Reel/Frame | Topical antibiotic composition providing optimal moisture environment for rapid wound healing that reduces skin contraction |
US5955414A (en) | 1994-10-05 | 1999-09-21 | S. C. Johnson & Son, Inc. | Cleaning foam having fluorinated stain repellent and low flammability |
US5540853A (en) | 1994-10-20 | 1996-07-30 | The Procter & Gamble Company | Personal treatment compositions and/or cosmetic compositions containing enduring perfume |
EP0738516A4 (en) | 1994-11-08 | 1997-01-15 | Mochida Pharm Co Ltd | External preparation for skin protection |
US5567420A (en) | 1994-11-16 | 1996-10-22 | Mceleney; John | Lotion which is temporarily colored upon application |
US5788664A (en) | 1994-11-30 | 1998-08-04 | Scalise; Gaspare | Suppository applicator |
GB9424562D0 (en) | 1994-12-06 | 1995-01-25 | Giltech Ltd | Product |
US5641480A (en) | 1994-12-08 | 1997-06-24 | Lever Brothers Company, Division Of Conopco, Inc. | Hair care compositions comprising heteroatom containing alkyl aldonamide compounds |
JP3355257B2 (en) | 1994-12-09 | 2002-12-09 | 太陽化学株式会社 | Cosmetics |
US5529770A (en) | 1994-12-09 | 1996-06-25 | West Agro, Inc. | Viscous liquid conditioning topical germicides |
DE4444238A1 (en) | 1994-12-13 | 1996-06-20 | Beiersdorf Ag | Cosmetic or dermatological drug combinations of cinnamic acid derivatives and flavone glycosides |
FR2728166A1 (en) | 1994-12-19 | 1996-06-21 | Oreal | TOPICAL COMPOSITION CONTAINING AN ANTAGONIST OF SUBSTANCE P |
US6455076B1 (en) | 1994-12-21 | 2002-09-24 | Gary S. Hahn | Formulations and methods for reducing skin irritation |
WO1996019921A1 (en) | 1994-12-23 | 1996-07-04 | Commonwealth Scientific And Industrial Research Organisation | Iodine biocidal material |
DE4446891A1 (en) | 1994-12-27 | 1996-07-04 | Falk Pharma Gmbh | Stable aqueous budesonide solution |
US5616136A (en) | 1995-01-09 | 1997-04-01 | Med-Safe Systems, Inc. | Quick release needle removal apparatus |
US5534261A (en) | 1995-01-17 | 1996-07-09 | University Of Southern California | Retinoid-based compositions and method for preventing adhesion formation using the same |
FR2729855A1 (en) | 1995-01-26 | 1996-08-02 | Oreal | USE OF A CGRP ANTAGONIST IN A COSMETIC, PHARMACEUTICAL OR DERMATOLOGICAL COMPOSITION AND COMPOSITION OBTAINED |
US5523078A (en) | 1995-02-03 | 1996-06-04 | Michael E. Baylin | Method of preparing and composition for treatment of hair and scalp |
US5587149A (en) | 1995-02-06 | 1996-12-24 | R.P. Scherer Corporation | Topical application emulsions |
FR2730932B1 (en) | 1995-02-27 | 1997-04-04 | Oreal | TRANSPARENT NANOEMULSION BASED ON FLUID NON-IONIC AMPHIPHILIC LIPIDS AND USE IN COSMETICS OR DERMOPHARMACY |
FR2730930B1 (en) | 1995-02-27 | 1997-04-04 | Oreal | USE OF NO-SYNTHASE INHIBITORS TO REDUCE THE IRRITANT SKIN EFFECT OF PRODUCTS USED IN THE COSMETIC OR PHARMACEUTICAL FIELD |
GB9504265D0 (en) | 1995-03-03 | 1995-04-19 | Medeva Plc | Corticosteroid-containing pharmaceutical composition |
US5558872A (en) | 1995-03-07 | 1996-09-24 | Healthpoint Medical Limited Partnership | Gelled mineral oil skin protectant |
US5618850A (en) | 1995-03-09 | 1997-04-08 | Focal, Inc. | Hydroxy-acid cosmetics |
US5783202A (en) | 1995-03-14 | 1998-07-21 | Soltec Research Pty. Ltd. | Pediculicidal mousse composition for killing head lice |
AU5013996A (en) | 1995-03-29 | 1996-10-16 | Shionogi & Co., Ltd. | Gelatin capsule with adjusted water activity |
JPH08277209A (en) | 1995-04-07 | 1996-10-22 | Taisho Pharmaceut Co Ltd | Revitalizing hair tonic |
US5585104A (en) | 1995-04-12 | 1996-12-17 | The Procter & Gamble Company | Cleansing emulsions |
EP0738510A3 (en) | 1995-04-20 | 2005-12-21 | L'oreal | Use of a HMG-CoA reductase inhibitor as an anti-ageing agent and as an anti-acne agent. Composition comprising at least one HMG-CoA reductase inhibitor and at least one active substance with scaling properties. |
FR2733417B1 (en) | 1995-04-25 | 1997-06-06 | Oreal | FOAMING OIL-IN-WATER EMULSION BASED ON NON-IONIC SURFACTANTS, A FATTY PHASE AND A CATIONIC OR ANIONIC POLYMER CROSS-LINKED AND USE IN TOPICAL APPLICATION |
GB9510856D0 (en) | 1995-05-27 | 1995-07-19 | Cussons Int Ltd | Cleaning composition |
UY24246A1 (en) | 1995-06-06 | 1996-06-14 | Neutrogena Corp | TROPIC VEHICLES CONTAINING SOLUBILIZED AND STABILIZED AZELAIC ACID |
CA2224798A1 (en) | 1995-06-22 | 1997-01-09 | Matthew T. Scholz | Stable hydroalcoholic compositions |
JP3542665B2 (en) | 1995-07-07 | 2004-07-14 | 株式会社資生堂 | Anti-aging skin external preparation, collagen cross-linking inhibition skin external preparation and anti-ultraviolet skin external preparation |
US5705472A (en) | 1995-07-18 | 1998-01-06 | Petroferm Inc. | Neutral aqueous cleaning composition |
FR2736824B1 (en) | 1995-07-18 | 1997-10-10 | Fabre Pierre Dermo Cosmetique | MINOXIDIL HAIR COMPOSITION WITH LOW FAT SOLVENT CONTENT |
DE29512760U1 (en) | 1995-08-08 | 1995-11-16 | Wella Ag | Pressurized gas container for dispensing foam |
TW504387B (en) | 1995-09-06 | 2002-10-01 | Kao Corp | Emulsified, water-in-oil type composition and skin cosmetic preparation |
CN1062129C (en) | 1995-09-14 | 2001-02-21 | 徐荣祥 | Medicine matrix and its use |
US5881493A (en) | 1995-09-14 | 1999-03-16 | D. B. Smith & Co. Inc. | Methods for applying foam |
JPH0984855A (en) | 1995-09-25 | 1997-03-31 | Kyoto Yakuhin Kogyo Kk | Aerosol preparation for administer medicine to rectum or vagina |
JPH0999553A (en) | 1995-10-09 | 1997-04-15 | Fujitsu Ltd | Ink jet head |
JP3425019B2 (en) | 1995-10-16 | 2003-07-07 | カネボウ株式会社 | Oily foam cleansing cosmetic |
US6221823B1 (en) | 1995-10-25 | 2001-04-24 | Reckitt Benckiser Inc. | Germicidal, acidic hard surface cleaning compositions |
CN1084613C (en) | 1995-12-14 | 2002-05-15 | 大正制药株式会社 | Aerosol preparation |
FR2742986B1 (en) | 1995-12-29 | 1998-01-30 | Rhone Poulenc Chimie | COSMETIC COMPOSITIONS FOR THE HAIR OR THE SKIN BASED ON SULPHONATED COPOLYESTERS WITH POLYORGANOSILOXANE MOTIFS |
US5716611A (en) | 1996-01-02 | 1998-02-10 | Euro-Celtique, S.A. | Emollient antimicrobial formulations containing povidone iodine |
US5889028A (en) | 1996-02-09 | 1999-03-30 | Mayo Foundation For Medical Education And Research | Colonic delivery of nicotine to treat inflammatory bowel disease |
US5843411A (en) | 1997-02-06 | 1998-12-01 | Topix Pharmaceuticals Inc. | Stabilization of ascorbic acid, ascorbic acid derivatives and/or extracts containing ascorbic acid for topical use |
US5759524A (en) | 1996-02-09 | 1998-06-02 | The Procter & Gamble Company | Photoprotective compositions |
US5846983A (en) | 1996-02-09 | 1998-12-08 | Mayo Foundation For Medical Education And Research | Colonic delivery of nicotine to treat inflammatory bowel disease |
AUPN814496A0 (en) | 1996-02-19 | 1996-03-14 | Monash University | Dermal penetration enhancer |
US5912007A (en) | 1996-02-29 | 1999-06-15 | Warner-Lambert Company | Delivery system for the localized administration of medicaments to the upper respiratory tract and methods for preparing and using same |
US6251369B1 (en) | 1996-03-05 | 2001-06-26 | Sultan Dental Products | Dental fluoride foam |
FR2745716B1 (en) | 1996-03-07 | 1998-04-17 | Oreal | ULTRAFINE PRESSURIZABLE FOAMING OIL-IN-WATER EMULSIONS |
US6251941B1 (en) | 1996-04-19 | 2001-06-26 | Sloan-Kettering Institute For Cancer Research | Use of inhaled retinoids in the prevention of cancer |
US5910382A (en) | 1996-04-23 | 1999-06-08 | Board Of Regents, University Of Texas Systems | Cathode materials for secondary (rechargeable) lithium batteries |
IT1283042B1 (en) | 1996-05-21 | 1998-04-07 | Condea Augusta Spa | COSMETIC COMPOUNDS DEODORANT AND / OR ANTI-BREATHING |
US5797955A (en) | 1996-06-11 | 1998-08-25 | Walters; David J. | Pressure application unit for positioning vertebra |
US5833961A (en) | 1996-06-25 | 1998-11-10 | Inolex Investment Corporation | Polyester-based suncreen formulations |
EP0932401A1 (en) | 1996-07-01 | 1999-08-04 | Sepracor, Inc. | Methods and compositions for treating urinary incontinence using enantiomerically enriched (r,r)-glycopyrrolate |
US5716621A (en) | 1996-07-03 | 1998-02-10 | Pharmadyn, Inc. | Nonocclusive drug delivery device and process for its manufacture |
EP0939618B1 (en) | 1996-07-10 | 2002-09-11 | Steris Inc. | Triclosan skin wash with enhanced efficacy |
DE19631221C2 (en) | 1996-08-02 | 1999-07-01 | Beiersdorf Ag | Foam-form sunscreen preparations containing water-soluble sunscreen filter substances and surface-active substances |
WO1998006419A1 (en) | 1996-08-15 | 1998-02-19 | Southern Illinois University | Enhancement of antimicrobial peptide activity by metal ions |
US5833963A (en) | 1996-08-20 | 1998-11-10 | Bristol-Myers Squibb Company | Non-tacky and quick-drying aqueous-based antiperspirant compositions |
US5741509A (en) | 1996-08-26 | 1998-04-21 | Alvin S. Berlat | Silicone wound dressing |
US5837270A (en) | 1996-08-26 | 1998-11-17 | Burgess; Nelson Leon | Topical anti-acne composition |
EP0829259A1 (en) | 1996-09-04 | 1998-03-18 | Warner-Lambert Company | Foam/gel with microbeads and/or fine particles |
US6271295B1 (en) | 1996-09-05 | 2001-08-07 | General Electric Company | Emulsions of silicones with non-aqueous hydroxylic solvents |
US5952392A (en) | 1996-09-17 | 1999-09-14 | Avanir Pharmaceuticals | Long-chain alcohols, alkanes, fatty acids and amides in the treatment of burns and viral inhibition |
US7060253B1 (en) | 1996-09-20 | 2006-06-13 | Mundschenk David D | Topical formulations and delivery systems |
FR2754451B1 (en) | 1996-10-14 | 1998-11-06 | Oreal | SELF-FOAMING CREAM |
AU4995597A (en) | 1996-10-23 | 1998-05-15 | Vertex Pharmaceuticals Incorporated | Methods of using sucrose octasulfate to treat or prevent enveloped virus infection |
US6093408A (en) | 1996-10-25 | 2000-07-25 | The Procter & Gamble Company | Skin care compositions |
IT1287114B1 (en) | 1996-10-31 | 1998-08-04 | Recordati Chem Pharm | ANTI-HERPETIC PHARMACEUTICAL COMPOSITIONS FOR TOPICAL APPLICATORS, CONTAINING ACICLOVIR |
WO1998019654A1 (en) | 1996-11-04 | 1998-05-14 | The Procter & Gamble Company | Hair mousse composition comprising silicone emulsion |
NZ335495A (en) | 1996-11-12 | 2002-03-28 | Dov Tamarkin | alpha,omega-dicarboxylic acid esters and their use in treating dermatological disorders |
FR2755854B1 (en) | 1996-11-15 | 1998-12-24 | Oreal | NANOEMULSION BASED ON NON-IONIC AND CATIONIC AMPHIPHILIC LIPIDS AND USES |
BR9707147A (en) | 1996-11-16 | 1999-04-06 | Wella Ag | Fiber dyeing and bleaching agent |
US5906992A (en) | 1996-11-21 | 1999-05-25 | Colgate Palmolive Company | Foam cleaning compositions |
AUPO379596A0 (en) | 1996-11-22 | 1996-12-19 | Soltec Research Pty Ltd | Percutaneous delivery system |
US5951544A (en) | 1996-12-04 | 1999-09-14 | Laser Industries Ltd. | Handpiece assembly for laser apparatus |
US5759579A (en) | 1996-12-05 | 1998-06-02 | American Home Products Corporation | Pharmaceutical suspension systems |
US5695551A (en) | 1996-12-09 | 1997-12-09 | Dow Corning Corporation | Water repellent composition |
US5856452A (en) | 1996-12-16 | 1999-01-05 | Sembiosys Genetics Inc. | Oil bodies and associated proteins as affinity matrices |
US5672634A (en) | 1996-12-23 | 1997-09-30 | Isp Investments Inc. | Crosslinked PVP-I2 foam product |
US5879469A (en) | 1997-01-06 | 1999-03-09 | Deeay Technologies Ltd. | Dishwashing method and detergent composition therefor |
US6582711B1 (en) | 1997-01-09 | 2003-06-24 | 3M Innovative Properties Company | Hydroalcoholic compositions thickened using polymers |
SE520811C2 (en) | 1997-01-17 | 2003-08-26 | Ponsus Ab | Skin protection preparations containing lipophilic and hydrophilic components, method of preparation and use thereof |
IN186803B (en) | 1997-02-05 | 2001-11-10 | Panacea Biotec Ltd | |
ES2133090B1 (en) | 1997-02-21 | 2000-04-01 | Uriach & Cia Sa J | NEW APPLICATOR FOR THE ADMINISTRATION OF SEMI-SOLID MEDICATIONS. |
CA2280179A1 (en) | 1997-02-11 | 1998-08-13 | Bernard Salafsky | Anti-parasitic action of n,n-diethyl-m-toluamide (deet) and formulations that prolong its activity in the skin |
CN100379423C (en) | 1997-02-24 | 2008-04-09 | S.L.A.药业股份公司 | Topical medicine composite containing cholinergic drug or calcium channel paralyser |
JP3050289B2 (en) | 1997-02-26 | 2000-06-12 | 日本電気株式会社 | Output impedance adjustment circuit of output buffer circuit |
US6433068B1 (en) | 1997-03-07 | 2002-08-13 | David S. Morrison | Hydrocarbon gels as suspending and dispersing agents and products |
FR2760637B1 (en) | 1997-03-11 | 1999-05-28 | Fabre Pierre Dermo Cosmetique | COAL TAR EXTRACT WITH REDUCED AROMATIC HYDROCARBON CONTENT, PROCESS FOR OBTAINING AND DERMO-COSMETIC PREPARATIONS |
US5922331A (en) | 1997-03-26 | 1999-07-13 | Chanel, Inc. | Skin cream composition |
US5951989A (en) | 1997-04-07 | 1999-09-14 | Heymann; Warren R. | Method for the treatment of dry skin |
USH2043H1 (en) | 1997-05-23 | 2002-08-06 | The Procter & Gamble Company | Skin care compositions |
US6599513B2 (en) | 1997-05-27 | 2003-07-29 | Sembiosys Genetics Inc. | Products for topical applications comprising oil bodies |
US6372234B1 (en) | 1997-05-27 | 2002-04-16 | Sembiosys Genetics Inc. | Products for topical applications comprising oil bodies |
US6146645A (en) | 1997-05-27 | 2000-11-14 | Sembiosys Genetics Inc. | Uses of oil bodies |
US6183762B1 (en) | 1997-05-27 | 2001-02-06 | Sembiosys Genetics Inc. | Oil body based personal care products |
JP3113610B2 (en) | 1997-06-04 | 2000-12-04 | 東洋ガスメーター株式会社 | Mounting fixture for transmission equipment for gas meters |
US6217887B1 (en) | 1997-06-04 | 2001-04-17 | The Procter & Gamble Company | Leave-on antimicrobial compositions which provide improved immediate germ reduction |
EP0884045A1 (en) | 1997-06-06 | 1998-12-16 | Pfizer Products Inc. | Self-tanning dihydroxyacetone formulations having improved stability and providing enhanced delivery |
US20050276836A1 (en) | 1997-06-11 | 2005-12-15 | Michelle Wilson | Coated vaginal devices for vaginal delivery of therapeutically effective and/or health-promoting agents |
AU729680B2 (en) | 1997-06-13 | 2001-02-08 | Taisho Pharmaceutical Co., Ltd. | Aerosol preparation |
JPH11111A (en) | 1997-06-13 | 1999-01-06 | Kagoshima Pref Gov | Feed for fish breeding |
FR2765799B1 (en) | 1997-07-08 | 1999-08-27 | Oreal | GLOSSY COMPOSITION CONTAINING AROMATIC OILS THICKENED BY A POLYSACCHARIDE ALKYLETHER |
DK1014916T4 (en) | 1997-08-18 | 2011-09-26 | Neubourg Skin Care Gmbh & Co Kg | The foam skin protection cream |
JP3553767B2 (en) | 1997-08-22 | 2004-08-11 | 三洋電機株式会社 | Transfer assistance device |
SE9703226D0 (en) | 1997-09-08 | 1997-09-08 | Astra Ab | New pharmaceutical composition |
US5885581A (en) | 1997-09-11 | 1999-03-23 | Merz, Incorporated | Composition and method for improvement of the appearance of scars |
US6241971B1 (en) | 1997-09-25 | 2001-06-05 | The Procter & Gamble Company | Hair styling compositions comprising mineral salt, lipophilic material, and low levels of surfactant |
US5939376A (en) | 1997-09-25 | 1999-08-17 | Colgate Palmolive Company | Liquid cleaning compositions containing an organic ester foam control agent |
US6214318B1 (en) | 1997-10-02 | 2001-04-10 | Oms Holdings Llc | Aerosol ointment compositions for topical use |
FR2769299B1 (en) | 1997-10-03 | 1999-12-31 | Oreal | BI-PRODUCTS PACKAGING AND DISTRIBUTION SET |
US6075056A (en) | 1997-10-03 | 2000-06-13 | Penederm, Inc. | Antifungal/steroid topical compositions |
AUPO983897A0 (en) | 1997-10-17 | 1997-11-06 | Soltec Research Pty Ltd | Topical antifungal composition |
US5961957A (en) | 1997-10-20 | 1999-10-05 | Mcanalley; Bill H. | Foam compositions |
US5911981A (en) | 1997-10-24 | 1999-06-15 | R.I.T.A. Corporation | Surfactant blends for generating a stable wet foam |
US5865347A (en) | 1997-10-27 | 1999-02-02 | William T. Wilkinson | Multi-chamber dispenser for flowable materials |
US5877216A (en) | 1997-10-28 | 1999-03-02 | Vivus, Incorporated | Treatment of female sexual dysfunction |
EP1027057A4 (en) | 1997-10-28 | 2003-01-02 | Vivus Inc | Treatment of female sexual dysfunction |
JP3450680B2 (en) | 1997-10-28 | 2003-09-29 | 高砂香料工業株式会社 | Method for producing para-menthane-3,8-diol |
KR100648536B1 (en) | 1997-11-10 | 2006-11-24 | 셀러지 파마세우티칼스, 인크 | Penetration enhancing and irritation reducing systems |
DE29720316U1 (en) | 1997-11-17 | 1998-01-29 | Andris Raimund Gmbh & Co Kg | Two-chamber dispenser |
US5849042A (en) | 1997-11-19 | 1998-12-15 | Bristol-Myers Squibb | Hair dye compositions containing 2,3 dialkyl-4-aminophenol and a 2-alkyl-1-naphthol |
US5871720A (en) | 1997-11-20 | 1999-02-16 | Colgate-Palmolive Company | Cosmetic compositions with DBS and functionalized silicones |
EP1049486A4 (en) | 1997-12-05 | 2006-01-04 | Lilly Co Eli | Glp-1 formulations |
TWI225793B (en) | 1997-12-25 | 2005-01-01 | Ajinomoto Kk | Cosmetic composition |
JP3050289U (en) | 1997-12-29 | 1998-06-30 | 丸隆株式会社 | Pet animal room excretion tools |
DE19802206A1 (en) | 1998-01-22 | 1999-07-29 | Beiersdorf Ag | Stable cosmetic or dermatological composition with low viscosity |
FR2774595A1 (en) | 1998-02-06 | 1999-08-13 | Rech D Innovation Et De Dev Ce | EMULSION FOR TRANSDERMAL STEROID ADMINISTRATION |
DE19805918A1 (en) | 1998-02-13 | 1999-08-19 | Beiersdorf Ag | Lipidreduced preparations |
US6110966A (en) | 1998-02-20 | 2000-08-29 | Medi-Cell Laboratories, Inc. | Triple action complex |
DE19807774A1 (en) | 1998-02-24 | 1999-08-26 | Beiersdorf Ag | Use of flavone, flavanone or flavonoid compound for protection of ascorbic acid or ascorbyl compound against oxidation, especially in cosmetic and dermatological preparations, |
JP3514105B2 (en) | 1998-02-27 | 2004-03-31 | ティアック株式会社 | Recording medium recording / reproducing device |
US6017912A (en) | 1998-02-27 | 2000-01-25 | Bussell; Letantia | Topical fluoroquinolone antibiotics in an alcohol and acetone vehicle |
CZ298971B6 (en) | 1998-03-04 | 2008-03-26 | Teijin Limited | Lotions based on Active vitamin D3 emulsions |
US6121210A (en) | 1998-03-12 | 2000-09-19 | Dap Products Inc. | Foamable silicone oil compositions and methods of use thereof |
DE69937339T2 (en) | 1998-03-12 | 2008-02-07 | Oji Paper Co., Ltd. | BACTERICIDAL |
US5990100A (en) | 1998-03-24 | 1999-11-23 | Panda Pharmaceuticals, L.L.C. | Composition and method for treatment of psoriasis |
AUPP310798A0 (en) | 1998-04-22 | 1998-05-14 | Soltec Research Pty Ltd | Vehicle system for a composition comprising a piperidinopyrimidine derivative |
US5919830A (en) | 1998-04-30 | 1999-07-06 | Gopalkrishnan; Sridhar | Stable non-aqueous blends for personal care compositions |
US6649175B1 (en) | 1998-05-04 | 2003-11-18 | Schering-Plough Healthcare Products, Inc. | Skin barrier composition |
GB9810949D0 (en) | 1998-05-22 | 1998-07-22 | Hewlett Healthcare Limited | Formulation |
FR2779637B1 (en) | 1998-06-15 | 2000-09-01 | Oreal | PHOTOPROTECTIVE COSMETIC COMPOSITIONS CONTAINING A METAL OXIDE NANOPIGMENT AND AN ACRYLIC TERPOLYMER AND USE OF SUCH COMPOSITIONS FOR PROTECTING KERATINIC MATERIALS FROM ULTRAVIOLET RADIATION |
US6706290B1 (en) | 1998-07-06 | 2004-03-16 | Olvai E. Kajander | Methods for eradication of nanobacteria |
FR2780879B1 (en) | 1998-07-09 | 2002-09-20 | Oreal | PHOTOPROTECTOR COSMETIC COMPOSITION CONTAINING AN ANIONIC SURFACTANT, COMPOUND FILTERING ULTRAVIOLET RADIATION AND CATIONIC OR ZPHITTERIONIC AMPHIPHILIC COMPOUND AND USE THEREOF |
US6146664A (en) | 1998-07-10 | 2000-11-14 | Shaklee Corporation | Stable topical ascorbic acid compositions |
US6124362A (en) | 1998-07-17 | 2000-09-26 | The Procter & Gamble Company | Method for regulating hair growth |
US6071541A (en) | 1998-07-31 | 2000-06-06 | Murad; Howard | Pharmaceutical compositions and methods for managing skin conditions |
DE19835239A1 (en) | 1998-08-04 | 2000-02-24 | Johnson & Johnson Gmbh | Foaming oil preparation and its use |
JP4017758B2 (en) | 1998-08-04 | 2007-12-05 | 高砂香料工業株式会社 | Cooling agent composition |
GB9817817D0 (en) | 1998-08-14 | 1998-10-14 | Unilever Plc | Cosmetic composition |
KR100604295B1 (en) | 1998-08-20 | 2006-07-28 | 쓰리엠 이노베이티브 프로퍼티즈 캄파니 | Spray On Bandage And Drug Delivery System |
JP3712868B2 (en) | 1998-09-02 | 2005-11-02 | 株式会社カネボウ化粧品 | Aerosol composition |
US8263580B2 (en) | 1998-09-11 | 2012-09-11 | Stiefel Research Australia Pty Ltd | Vitamin formulation |
AUPP583198A0 (en) | 1998-09-11 | 1998-10-01 | Soltec Research Pty Ltd | Mousse composition |
US6087310A (en) | 1998-09-23 | 2000-07-11 | Castrol Limited | Skin cleaning compositions and uses comprising a polymer latex emulsion |
EP1117398A2 (en) | 1998-09-28 | 2001-07-25 | Merck & Co., Inc. | A method for treating inflammatory diseases by administering a thrombin inhibitor |
US6914057B1 (en) | 1998-09-28 | 2005-07-05 | The Research Foundation Of State University Of New York | Inhibitor of cataract formation |
US6607716B1 (en) | 1998-09-29 | 2003-08-19 | Tech Labs, Inc. | Pediculicidal compositions, a kit, and methods of use |
RU2134052C1 (en) | 1998-10-07 | 1999-08-10 | Нерушай Сергей Алексеевич | Method and apparatus for aerosol application of perfumery liquids |
US6287546B1 (en) | 1998-10-09 | 2001-09-11 | Colgate-Palmolive Company | Shampoos with stabilizers |
JP3876081B2 (en) | 1998-10-22 | 2007-01-31 | 東洋エアゾール工業株式会社 | Aerosol composition for foam formation |
US6110477A (en) | 1998-10-30 | 2000-08-29 | Topix Pharmaceuticals Inc. | Stabilization of ascorbic acid, ascorbic acid derivatives and/or extracts containing ascorbic acid for topical use |
US7521068B2 (en) | 1998-11-12 | 2009-04-21 | Elan Pharma International Ltd. | Dry powder aerosols of nanoparticulate drugs |
US5980904A (en) | 1998-11-18 | 1999-11-09 | Amway Corporation | Skin whitening composition containing bearberry extract and a reducing agent |
US6344218B1 (en) | 1998-11-23 | 2002-02-05 | The Procter & Gamble Company | Skin deodorizing and santizing compositions |
DE19855097A1 (en) | 1998-11-28 | 2000-05-31 | Wella Ag | Pigment-containing, foamable gel |
US20010006654A1 (en) | 1998-12-09 | 2001-07-05 | L'oreal | Compositions and methods for treating hair and skin using aqueous delivery systems |
US6486207B2 (en) | 1998-12-10 | 2002-11-26 | Nexmed (Holdings), Inc. | Compositions and methods for amelioration of human female sexual dysfunction |
US6087317A (en) | 1998-12-10 | 2000-07-11 | Dow Corning Corporation | Particle size stable silicone emulsions |
US6262128B1 (en) | 1998-12-16 | 2001-07-17 | 3M Innovative Properties Company | Aqueous foaming compositions, foam compositions, and preparation of foam compositions |
FR2787325B1 (en) | 1998-12-17 | 2001-01-26 | Oreal | NANOEMULSION BASED ON OXYETHYLENE OR NON-OXYETHYLENE SORBITAN FATTY ESTERS, AND ITS USES IN THE COSMETIC, DERMATOLOGICAL AND / OR OPHTHALMOLOGICAL FIELDS |
FR2787728B1 (en) | 1998-12-23 | 2001-01-26 | Oreal | NANOEMULSION BASED ON FATTY ESTERS OF PHOSPHORIC ACID, AND ITS USES IN THE COSMETIC, DERMATOLOGICAL, PHARMACEUTICAL AND / OR OPHTHALMOLOGICAL FIELDS |
JP2000191429A (en) | 1998-12-28 | 2000-07-11 | Kao Corp | Foamable cosmetic |
CN1195550C (en) | 1998-12-28 | 2005-04-06 | 大正制药株式会社 | External preparation |
FR2787703B1 (en) | 1998-12-29 | 2001-01-26 | Oreal | NANOEMULSION BASED ON ETHOXYL FATHER ETHERS OR ETHOXYL FATTY ESTERS, AND ITS USES IN THE COSMETIC, DERMATOLOGICAL AND / OR OPHTHALMOLOGICAL FIELDS |
FR2788007B1 (en) | 1999-01-05 | 2001-02-09 | Oreal | NANOEMULSION BASED ON BLOCK COPOLYMERS OF ETHYLENE OXIDE AND PROPYLENE OXIDE, AND ITS USES IN THE COSMETIC, DERMATOLOGICAL AND / OR OPHTHALMOLOGICAL FIELDS |
US6270781B1 (en) | 1999-01-08 | 2001-08-07 | Maxim Pharmaceuticals, Inc. | Method and compositions for topical treatment of damaged tissue using reactive oxygen metabolite production or release inhibitors |
US6486168B1 (en) | 1999-01-08 | 2002-11-26 | 3M Innovative Properties Company | Formulations and methods for treatment of mucosal associated conditions with an immune response modifier |
FR2789371B1 (en) | 1999-02-05 | 2001-04-27 | Sofab | DISTRIBUTOR OF CHEMICALLY UNSTABLE PRODUCTS |
EP1025836A1 (en) | 1999-02-08 | 2000-08-09 | F. Hoffmann-La Roche Ag | Cosmetic light screening composition |
TWI262930B (en) | 1999-02-10 | 2006-10-01 | Mitsui Chemicals Inc | High-durability flexible polyurethane cold molded foam and process for producing the same |
US6224888B1 (en) | 1999-02-12 | 2001-05-01 | The Procter & Gamble Company | Cosmetic compositions |
US6423329B1 (en) | 1999-02-12 | 2002-07-23 | The Procter & Gamble Company | Skin sanitizing compositions |
JP3641152B2 (en) | 1999-02-17 | 2005-04-20 | 株式会社ヤクルト本社 | Topical skin preparation |
US6761903B2 (en) | 1999-06-30 | 2004-07-13 | Lipocine, Inc. | Clear oil-containing pharmaceutical compositions containing a therapeutic agent |
DE50004303D1 (en) | 1999-02-26 | 2003-12-11 | Wella Ag | DEVICE FOR MIXING, FOAMING AND DISPENSING LIQUIDS FROM SEPARATE PRESSURE GAS TANKS |
US7374779B2 (en) | 1999-02-26 | 2008-05-20 | Lipocine, Inc. | Pharmaceutical formulations and systems for improved absorption and multistage release of active agents |
IL129102A0 (en) | 1999-03-22 | 2000-02-17 | J P M E D Ltd | An emulsion |
ES2272209T3 (en) | 1999-03-31 | 2007-05-01 | Firmenich Sa | USE OF CUBEBOL AS AROMATIZING INGREDIENT. |
US6383471B1 (en) | 1999-04-06 | 2002-05-07 | Lipocine, Inc. | Compositions and methods for improved delivery of ionizable hydrophobic therapeutic agents |
US6264964B1 (en) | 1999-04-14 | 2001-07-24 | Conopco, Inc. | Foaming cosmetic products |
WO2000062776A1 (en) | 1999-04-16 | 2000-10-26 | Fujisawa Pharmaceutical Co., Ltd. | Antifungal compositions |
US6284802B1 (en) | 1999-04-19 | 2001-09-04 | The Procter & Gamble Company | Methods for regulating the condition of mammalian keratinous tissue |
US6433003B1 (en) | 1999-04-23 | 2002-08-13 | Arthur M. Bobrove | Method for treating hyperhidrosis in mammals |
EP1178808B2 (en) | 1999-04-23 | 2019-06-12 | Leo Pharma A/S | Non-aqueous pharmaceutical composition for dermal use to treat psoriasis comprising a vitamin d, a corticosteroid and a solvent component |
GB9909711D0 (en) | 1999-04-27 | 1999-06-23 | Unilever Plc | Mousse forming hair treatment composition |
FR2793479B1 (en) | 1999-05-10 | 2001-06-29 | Lir France Sa | DOUBLE DISPENSER FOR FLUID OR PASTY PRODUCTS |
AU4841700A (en) | 1999-05-12 | 2000-11-21 | Nitromed, Inc. | Nitrosated and nitrosylated potassium channel activators, compositions and methods of use |
US6168576B1 (en) | 1999-05-24 | 2001-01-02 | Irene N. Reynolds | Device for dispensing vaginal medication |
US6395300B1 (en) | 1999-05-27 | 2002-05-28 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
US6518228B1 (en) | 1999-05-27 | 2003-02-11 | Clairol Incorporated | Ultra-mild, clear, aqueous, foamable skin cleanser |
ATE300274T1 (en) | 1999-05-28 | 2005-08-15 | Unilever Nv | FOAMABLE SHOWER OIL COMPOSITION |
JP2000351726A (en) | 1999-06-08 | 2000-12-19 | Lion Corp | Aerosol preparation |
JP2000354623A (en) | 1999-06-14 | 2000-12-26 | Shiigeru Kk | Deodorant and deodorizing spray |
US6113888A (en) | 1999-06-15 | 2000-09-05 | Neutrogena Corporation | Self-tanning mousse |
GB9913951D0 (en) | 1999-06-15 | 1999-08-18 | Unilever Plc | Mousse-forming shampoo compositions |
KR100352088B1 (en) | 1999-06-21 | 2002-09-12 | 한미약품공업 주식회사 | Dermal emulsion composition comprising minoxidil |
US6190365B1 (en) | 1999-06-21 | 2001-02-20 | Chun Lim Abbott | Vaginal douche applicator and method of vaginal deodorization using the same |
NL1012419C2 (en) | 1999-06-23 | 2000-12-28 | Airspray Nv | Aerosol for dispensing a liquid. |
US6524594B1 (en) | 1999-06-23 | 2003-02-25 | Johnson & Johnson Consumer Companies, Inc. | Foaming oil gel compositions |
JP2001002526A (en) | 1999-06-23 | 2001-01-09 | Koike Kagaku Kk | Foam aerosol composition |
US6551604B1 (en) | 1999-06-28 | 2003-04-22 | The Procter & Gamble Company | Skin care compositions |
US6762158B2 (en) | 1999-07-01 | 2004-07-13 | Johnson & Johnson Consumer Companies, Inc. | Personal care compositions comprising liquid ester mixtures |
WO2001001949A1 (en) | 1999-07-01 | 2001-01-11 | Johnson And Johnson Consumer Companies, Inc. | Cleansing compositions |
FR2795643B1 (en) | 1999-07-02 | 2004-06-11 | Oreal | FIRMING COSMETIC COMPOSITION INCLUDING AT LEAST ONE HYDROXYSTILBENE IN ASSOCIATION WITH ASCORBIC ACID |
JP4058199B2 (en) | 1999-07-06 | 2008-03-05 | ポーラ化成工業株式会社 | Warm feeling pack |
CA2313955A1 (en) | 1999-07-15 | 2001-01-15 | Playtex Products, Inc. | Sunscreen aerosol composition |
US6548074B1 (en) | 1999-07-22 | 2003-04-15 | Elizabeth Arden Co., Division Of Conopco, Inc. | Silicone elastomer emulsions stabilized with pentylene glycol |
FR2796925B1 (en) | 1999-07-29 | 2001-10-05 | Valois Sa | DISPENSER WITH ARTICULATED DISPENSING HEAD |
WO2001008681A1 (en) | 1999-08-02 | 2001-02-08 | First Horizon Pharmaceutical Corporation | Methods of administration of glycopyrrolate compositions |
US6303552B1 (en) | 1999-08-04 | 2001-10-16 | Napier International Technologies, Inc. | Aerosol paint stripper compositions |
DE19938757A1 (en) | 1999-08-16 | 2001-02-22 | Beiersdorf Ag | Cosmetic or dermatological preparations of the oil-in-water type |
ATE270558T1 (en) | 1999-08-26 | 2004-07-15 | Ganeden Biotech Inc | USE OF EMU OIL AS A CARRIER FOR FUNGICIDES, ANTIBACTERIAL AND ANTIVIRAL MEDICATIONS |
US6777591B1 (en) | 1999-08-27 | 2004-08-17 | Sembiosys Genetics Inc. | Legume-like storage protein promoter isolated from flax and methods of expressing proteins in plant seeds using the promoter |
US6479058B1 (en) | 1999-09-02 | 2002-11-12 | Mccadden Michael E. | Composition for the topical treatment of poison ivy and other forms of contact dermatitis |
US6308863B1 (en) | 1999-09-02 | 2001-10-30 | Owens-Brockway Plastic Products Inc. | Dual chamber package for pressurized products |
JP4394775B2 (en) | 1999-09-03 | 2010-01-06 | 株式会社ダイゾー | Water-in-oil foam aerosol composition and method for producing the same |
JP4045475B2 (en) | 1999-09-06 | 2008-02-13 | 東洋紡績株式会社 | Nucleic acid / protein purification equipment |
US6986883B2 (en) | 1999-09-09 | 2006-01-17 | Discus Dental, Inc. | Increased peroxide content tooth bleaching gel |
AU3887301A (en) | 1999-09-20 | 2001-04-24 | Procter & Gamble Company, The | Article for the delivery of foam products |
US6437006B1 (en) | 1999-09-27 | 2002-08-20 | American Cyanamid Company | Pharmaceutical carrier formulation |
US6528086B2 (en) | 1999-09-28 | 2003-03-04 | Zars, Inc. | Methods and apparatus for drug delivery involving phase changing formulations |
FR2798849B1 (en) | 1999-09-29 | 2001-11-23 | Oreal | COMPOSITION FOR WASHING KERATIN MATERIALS, BASED ON A DETERGENT SURFACE-ACTIVE AGENT, A DIALKYL DIALLYL AMMONIUM HOMOPOLYMER AND AN ACRYLIC TERPOLYMER |
US6790435B1 (en) | 1999-10-01 | 2004-09-14 | Unilever Home & Personal Care Usa Division Of Conopco, Inc. | Antiperspirant compositions comprising microemulsions |
US6667045B2 (en) | 1999-10-01 | 2003-12-23 | Joseph Scott Dahle | Topical applications for skin treatment |
FR2799369B1 (en) | 1999-10-08 | 2001-12-21 | Oreal | COMBINATION OF ESCINE AND DEXTRAN SULFATE AND THE USE THEREOF |
US6186367B1 (en) | 1999-10-19 | 2001-02-13 | Valley Design Inc. | Metered liquid squeeze dispenser |
FR2799963B1 (en) | 1999-10-22 | 2002-07-19 | Oreal | EMULSIONS CONTAINING AT LEAST ONE INSOLUBLE ORGANIC UV FILTER AND A NON-FILTERING ORGANOMODIFIED SILICONE |
US6080394A (en) | 1999-11-08 | 2000-06-27 | Dow Corning Corporation | Polar solvent-in-oil emulsions and multiple emulsions |
US20030077301A1 (en) | 1999-12-16 | 2003-04-24 | Maibach Howard I. | Topical pharmaceutical composition for the treatment of inflammatory dermatoses |
UA66796C2 (en) | 1999-12-27 | 2004-06-15 | Univ Nat Pharmaceutical | Composition "profesol foamy" for treating radiation lesions of skin |
US6967023B1 (en) | 2000-01-10 | 2005-11-22 | Foamix, Ltd. | Pharmaceutical and cosmetic carrier or composition for topical application |
IL133969A0 (en) | 2000-01-10 | 2001-04-30 | Thixo Ltd | Thixotropic compositions containing unsaturated oils and food products containing the same |
US6528033B1 (en) | 2000-01-18 | 2003-03-04 | Valence Technology, Inc. | Method of making lithium-containing materials |
US7001690B2 (en) | 2000-01-18 | 2006-02-21 | Valence Technology, Inc. | Lithium-based active materials and preparation thereof |
FR2804015B1 (en) | 2000-01-21 | 2005-12-23 | Oreal | NANEMULSION CONTAINING AMPHIPHILIC LIPIDS AND NONIONIC POLYMER AND USES THEREOF |
FR2804016B1 (en) | 2000-01-21 | 2006-07-28 | Oreal | NANEMULSION CONTAINING AMPHIPHILIC LIPIDS AND PEG ESTER AND USES THEREOF |
AU2001231189A1 (en) | 2000-01-27 | 2001-08-07 | Childrens Hospital Research Foundation | Transdermal anesthetic and vasodilator composition and methods for topical administration |
FR2804666B1 (en) | 2000-02-04 | 2002-06-14 | Oreal | DISPENSER FOR STORING AT LEAST TWO COMPONENTS AND SELECTIVE DISPENSING EITHER OF A SINGLE CONSTITUENT, EITHER OF THEIR MIXTURE, AND METHOD FOR THE IMPLEMENTATION THEREOF |
US6780443B1 (en) | 2000-02-04 | 2004-08-24 | Takasago International Corporation | Sensate composition imparting initial sensation upon contact |
NL1014389C2 (en) | 2000-02-15 | 2001-08-16 | Dija Zeist Bv | Tanning preparation for the skin. |
US20040161447A1 (en) | 2000-02-17 | 2004-08-19 | Leonard Paul | Liquid foam producing compositions and dispensing system therefor |
DE60105362T2 (en) | 2000-02-22 | 2005-02-17 | Color Access, Inc. | AQUEOUS COSMETIC GEL |
WO2001063479A1 (en) | 2000-02-22 | 2001-08-30 | Metacarta, Inc. | Spatially coding and displaying information |
DE10008896A1 (en) | 2000-02-25 | 2001-08-30 | Beiersdorf Ag | Improving the solubility and compatibility of benzotriazole UV filters in oils, e.g. in cosmetics or dermatological compositions, by addition of dialkylnaphthalates |
DE10008837A1 (en) | 2000-02-25 | 2001-08-30 | Henkel Kgaa | Dental cleaner containing propellant gas |
US6664287B2 (en) | 2000-03-15 | 2003-12-16 | Bethesda Pharmaceuticals, Inc. | Antioxidants |
IL135222A (en) | 2000-03-22 | 2005-06-19 | Univ Ben Gurion | Compositions containing molecular iodine |
DE20006099U1 (en) | 2000-04-01 | 2000-07-06 | Megaplast Gmbh & Co Kg | Dosing pump dispenser with at least two dosing pumps |
US6649571B1 (en) | 2000-04-04 | 2003-11-18 | Masi Technologies, L.L.C. | Method of generating gas bubbles in oleaginous liquids |
US6437004B1 (en) | 2000-04-06 | 2002-08-20 | Nicholas V. Perricone | Treatment of skin damage using olive oil polyphenols |
FR2807322B1 (en) | 2000-04-10 | 2004-02-20 | Oreal | COMPOSITION, ESPECIALLY COSMETIC, COMPRISING ASCORBIC ACID IN ASSOCIATION WITH AN ASCORBIC ACID DERIVATIVE |
US7758888B2 (en) | 2000-04-21 | 2010-07-20 | Sol-Gel Technologies Ltd. | Composition exhibiting enhanced formulation stability and delivery of topical active ingredients |
JP2002012513A (en) | 2000-04-24 | 2002-01-15 | Kanebo Ltd | Urea-containing whipped cosmetic |
US6358541B1 (en) | 2000-05-03 | 2002-03-19 | David S. Goodman | Topical preparation for the treatment of hair loss |
US6410036B1 (en) | 2000-05-04 | 2002-06-25 | E-L Management Corp. | Eutectic mixtures in cosmetic compositions |
EP1278504A2 (en) | 2000-05-05 | 2003-01-29 | R.P. Scherer Technologies, Inc. | Oil-in-water emulsion formulation containing hydroquinone and retinol |
ATE338577T1 (en) | 2000-05-08 | 2006-09-15 | Pfizer Prod Inc | SPRAYABLE SKIN PROTECTIVE |
US6433024B1 (en) | 2000-05-08 | 2002-08-13 | Karl F. Popp | Topical anti-acne composition |
FR2808685B1 (en) | 2000-05-12 | 2004-10-08 | Sanofi Synthelabo | PHARMACEUTICAL COMPOSITIONS FOR TRANSDERMAL DELIVERY OF ANTI-INFLAMMATORY AGENTS |
JP2001326952A (en) | 2000-05-15 | 2001-11-22 | Nec Corp | Broadcast confirmation system, method and device for broadcast confirmation, and recording medium with broadcast confirmation program recorded thereon |
FR2809010B1 (en) | 2000-05-22 | 2002-07-12 | Oreal | NANOEMULSION BASED ON ANIONIC POLYMERS, AND ITS USES IN PARTICULAR IN THE COSMETIC, DERMATOLOGICAL, PHARMACEUTICAL AND / OR OPHTHALMOLOGICAL FIELDS |
JP4653282B2 (en) | 2000-05-23 | 2011-03-16 | 昭和薬品化工株式会社 | Minocycline-containing composition |
DE10028638A1 (en) | 2000-06-09 | 2001-12-20 | Schuelke & Mayr Gmbh | Storage-stable composition useful in cosmetic and pharmaceutical compositions comprises combination of glycerol monoalkyl ether with antioxidant |
AU2001268451A1 (en) | 2000-06-13 | 2001-12-24 | Fd Management, Inc. | Cosmetic composition for stressed skin under extreme conditions |
US6818204B2 (en) | 2000-06-23 | 2004-11-16 | Combe Incorporated | Stable foam for use in disposable wipe |
US20020164381A1 (en) | 2000-06-30 | 2002-11-07 | Medicis Pharmaceutical Corporation | Mitocidal compositions and methods |
US8512718B2 (en) | 2000-07-03 | 2013-08-20 | Foamix Ltd. | Pharmaceutical composition for topical application |
CA2313659A1 (en) | 2000-07-06 | 2002-01-06 | Barry J. Barclay | B complex vitamin compositions that protect against cellular damage caused by ultraviolet light |
DE10033414B4 (en) | 2000-07-08 | 2004-02-19 | Wella Aktiengesellschaft | Clear, two-phase, foam-forming aerosol hair care product |
FR2811564B1 (en) | 2000-07-13 | 2002-12-27 | Oreal | NANOEMULSION CONTAINING NON-IONIC POLYMERS, AND ITS USES IN PARTICULAR IN THE COSMETIC, DERMATOLOGICAL, PHARMACEUTICAL AND / OR OPHTHALMOLOGICAL FIELDS |
US6468989B1 (en) | 2000-07-13 | 2002-10-22 | Dow Pharmaceutical Sciences | Gel compositions containing metronidazole |
DE10035930A1 (en) | 2000-07-21 | 2002-01-31 | Clariant Gmbh | fine emulsions |
US20020035070A1 (en) | 2000-07-26 | 2002-03-21 | The Procter & Gamble Company | Method of regulating hair growth using metal complexes of oxidized carbohydrates |
FR2812191B1 (en) | 2000-07-28 | 2003-10-17 | Oreal | USE OF PROSTAGLANDIN E2 RECEPTOR AGONISTS (EP-3) TO ATTENUATE, DECREASE OR STOP HAIR AND HAIR GROWTH IN COSMETIC PREPARATIONS |
JP4166931B2 (en) | 2000-08-02 | 2008-10-15 | ポーラ化成工業株式会社 | Fever foam cosmetic |
US20040198706A1 (en) | 2003-03-11 | 2004-10-07 | Carrara Dario Norberto R. | Methods and formulations for transdermal or transmucosal application of active agents |
US6514487B1 (en) | 2000-08-08 | 2003-02-04 | Teresa Leigh Barr | Foam and gel oat protein complex and method of use |
AU2001285201A1 (en) | 2000-08-22 | 2002-03-04 | The Procter And Gamble Company | Personal care compositions containing adhesive elastomeric polymer and inorganic colloid |
AU2001286578A1 (en) | 2000-08-24 | 2002-03-04 | Tim Ioannides | Topical antioxidant having vitamin c and method of combination with topical agent by user |
US6299023B1 (en) | 2000-08-24 | 2001-10-09 | Miles Arnone | Device for dispensing two substances in a user selectable ratio with replaceable cartridges |
FR2813189B1 (en) | 2000-08-31 | 2003-02-28 | Oreal | COSMETIC FOAMING CREAM FOR THE TREATMENT OF OILY SKIN |
AU2001290936A1 (en) | 2000-09-14 | 2002-03-26 | Quantum Energy Technologies | Application of water nanoclusters to skin |
EP1319397B1 (en) | 2000-09-21 | 2005-08-17 | Taisho Pharmaceutical Co., Ltd | Suppositories sustained in the lower rectum |
AUPR048600A0 (en) | 2000-10-02 | 2000-10-26 | Soltec Research Pty Ltd | Pharmaceutical vehicle |
DE10049147A1 (en) | 2000-10-04 | 2002-04-25 | Wella Ag | Hair wax product with waxes, non-volatile oils and volatile, hydrophobic substances |
FR2814959A1 (en) | 2000-10-09 | 2002-04-12 | Menarini France | Atomiser for pharmaceutical products based on antiinflammatory agents comprises pressurized container, dosing pouch and metering valve |
US6547063B1 (en) | 2000-10-10 | 2003-04-15 | The Procter & Gamble Company | Article for the delivery of foam products |
GB2367809A (en) | 2000-10-12 | 2002-04-17 | Bespak Plc | Metering valve with collapsible chamber |
US6403069B1 (en) | 2000-10-20 | 2002-06-11 | Colgate-Palmolive Company | High oil clear emulsion with elastomer |
FR2815616B1 (en) | 2000-10-20 | 2003-01-24 | Oreal | DISTRIBUTION ASSEMBLY FOR THE EXTEMPORARY DISTRIBUTION OF TWO PRODUCTS |
US20040018228A1 (en) | 2000-11-06 | 2004-01-29 | Afmedica, Inc. | Compositions and methods for reducing scar tissue formation |
DE10058384B4 (en) | 2000-11-24 | 2004-12-16 | Wella Aktiengesellschaft | Cosmetic or dermatological agent in the form of a creamy permanent foam or a stably foamed cream, its use and method for producing the agent |
US6299032B1 (en) | 2000-11-27 | 2001-10-09 | George W. Hamilton | Disposable actuator with cap opener for aerosol cans |
US6969521B1 (en) | 2000-11-28 | 2005-11-29 | Avon Products, Inc. | Aerosol insect repellent composition having low VOC content and method of applying same to the skin |
AU2002217896A1 (en) | 2000-11-28 | 2002-06-11 | Avon Products Inc. | Foaming insect repellent compositions |
US20050013853A1 (en) | 2000-11-29 | 2005-01-20 | Irit Gil-Ad | Anti-proliferative drugs |
US6774100B2 (en) | 2000-12-06 | 2004-08-10 | Imaginative Research Associates, Inc. | Anhydrous creams, lotions and gels |
GB0030068D0 (en) | 2000-12-11 | 2001-01-24 | Lawrence Malcolm | Highway vehicular traffic flow control |
JP3497466B2 (en) | 2000-12-12 | 2004-02-16 | 高砂香料工業株式会社 | Warming composition |
US20060254597A1 (en) | 2000-12-14 | 2006-11-16 | 40J's Llc | Method of treatment of atrophic vaginitis by topical clitoral menthol or a related cooling compound |
DE10063342A1 (en) | 2000-12-19 | 2002-06-20 | Beiersdorf Ag | Cosmetic or dermatological composition contains three-part emulsifier system and gas |
US6749860B2 (en) | 2000-12-22 | 2004-06-15 | Kimberly-Clark Worldwide, Inc. | Absorbent articles with non-aqueous compositions containing botanicals |
US20040079361A1 (en) | 2001-01-17 | 2004-04-29 | Clayton Colin D. | Medicinal aerosols |
FR2819427B1 (en) | 2001-01-18 | 2003-04-11 | Oreal | TRANSLUCENT NANOEMULSION, MANUFACTURING METHOD THEREOF AND USES THEREOF IN THE COSMETIC, DERMATOLOGICAL AND / OR OPHTHALMOLOGICAL FIELDS |
US20030013692A1 (en) | 2001-01-19 | 2003-01-16 | Gullans Steven R. | Methods of treating neurological disorders |
CA2437380A1 (en) | 2001-02-05 | 2002-08-15 | Michael Albert Kamm | A treatment of oesophageal motility disorders and gastro-oesophageal reflux disease |
DE10110336A1 (en) | 2001-03-03 | 2002-09-12 | Clariant Gmbh | Surfactant-free cosmetic, dermatological and pharmaceutical agents |
KR20040052489A (en) | 2001-03-06 | 2004-06-23 | 셀러지 파마세우티칼스, 인크 | Compounds and methods for the treatment of urogenital disorders |
JP2004520437A (en) | 2001-03-07 | 2004-07-08 | ザ プロクター アンド ギャンブル カンパニー | Topical composition containing functional aromatic derivative cosmetic binder |
ATE273206T1 (en) | 2001-03-26 | 2004-08-15 | 3M Innovative Properties Co | DOSSIER VALVE FOR AN IMPROVED FLOW DOSAGE INHALER |
AU2002254396A1 (en) | 2001-03-26 | 2002-10-08 | Dana-Farber Cancer Institute, Inc. | Method of attenuating reactions to skin irritants |
US6951654B2 (en) | 2001-03-27 | 2005-10-04 | Galen (Chemicals) Limited | Intravaginal drug delivery devices for the administration of an antimicrobial agent |
US6977082B2 (en) | 2001-03-29 | 2005-12-20 | The Dial Corporation | High efficacy antibacterial compositions having enhanced esthetic and skin care properties |
JP2002302419A (en) | 2001-03-30 | 2002-10-18 | Aldeep Cosmetics Japan Inc | Cosmetic composition |
CA2447008A1 (en) | 2001-04-05 | 2002-10-24 | Collagenex Pharmaceuticals, Inc. | Controlled delivery of tetracycline compounds and tetracycline derivatives |
US6848597B2 (en) | 2001-04-18 | 2005-02-01 | James A. Vlodek | Methods and apparatus for extruding foam through orifices |
US20030053980A1 (en) | 2001-04-30 | 2003-03-20 | The Gillette Company | Shaving compositions containing highly lubricious water soluble polymers |
US6682726B2 (en) | 2001-04-30 | 2004-01-27 | The Gillette Company | Self-foaming shaving lotion |
US7078048B2 (en) * | 2001-05-09 | 2006-07-18 | The Regents Of The University Of Michigan | Method and compositions for treating rosacea |
US20020187181A1 (en) | 2001-05-14 | 2002-12-12 | 3M Innovative Properties Company | System for delivering cosmetics and pharmaceuticals |
ITMI20011019A1 (en) | 2001-05-17 | 2002-11-17 | Carlo Ghisalberti | FURILIC SUBSTANCES FOR TOPICAL USE |
US20030017181A1 (en) | 2001-05-31 | 2003-01-23 | Rood Gloria A. | Dermatological compositions and methods |
JP2005501022A (en) | 2001-06-20 | 2005-01-13 | ザ プロクター アンド ギャンブル カンパニー | Personal care composition comprising a polyol-in-silicone emulsion |
US7270828B2 (en) | 2001-06-20 | 2007-09-18 | The Procter & Gamble Company | Personal care composition comprising hydrophobic gel |
FR2826292B1 (en) | 2001-06-22 | 2004-01-23 | Rhodia Chimie Sa | OIL-IN-OIL EMULSIONS COMPRISING A SILICONE, DISPERSIONS OF SUCH EMULSIONS AND USE THEREOF |
US6428772B1 (en) | 2001-06-25 | 2002-08-06 | Blistex Inc. | Acne treatment composition with cooling effect |
US6544562B2 (en) | 2001-06-25 | 2003-04-08 | Blistex Inc. | Acne treatment including dual-package system |
WO2003002082A1 (en) | 2001-06-26 | 2003-01-09 | The Procter & Gamble Company | Pressurized anhydrous antiperspirant emulsions |
JP4051412B2 (en) | 2001-06-27 | 2008-02-27 | 株式会社カネボウ化粧品 | Mixed dispenser |
JP2003012511A (en) | 2001-06-27 | 2003-01-15 | Rohto Pharmaceut Co Ltd | Aerosol composition |
JP2004536839A (en) | 2001-07-13 | 2004-12-09 | ザ プロクター アンド ギャンブル カンパニー | Mousse-forming compositions containing quaternary ammonium agents |
US20060194773A1 (en) | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
DE10134786A1 (en) | 2001-07-17 | 2003-02-06 | Beiersdorf Ag | Foamable preparations |
CA2456029C (en) | 2001-08-03 | 2010-12-07 | Takeda Chemical Industries, Ltd. | Stable emulsion composition |
DE10138495B4 (en) | 2001-08-04 | 2004-11-11 | Beiersdorf Ag | Foaming preparations and their use |
DK1424067T3 (en) | 2001-08-08 | 2010-08-30 | Dominguez Maria Antonia Garcia-Olmedo | Injectable foam and novel pharmaceutical applications thereof |
JP4707279B2 (en) | 2001-08-09 | 2011-06-22 | ポーラ化成工業株式会社 | Cosmetics for massage with cool-down effect |
US7091243B2 (en) | 2001-08-09 | 2006-08-15 | Croda, Inc. | Anti-irritants |
CA2457049A1 (en) | 2001-08-11 | 2003-02-20 | Samir Mizban | Pressurised aerosol dispenser |
US6638981B2 (en) | 2001-08-17 | 2003-10-28 | Epicept Corporation | Topical compositions and methods for treating pain |
US20030049218A1 (en) | 2001-08-28 | 2003-03-13 | Amit Patel | Antiperspirant deodorant emulsion |
DE60232178D1 (en) | 2001-08-29 | 2009-06-10 | Pharmakodex Ltd | DEVICE FOR TOPICAL ADMINISTRATION |
US6709663B2 (en) | 2001-08-31 | 2004-03-23 | Healthpoint, Ltd. | Multivesicular emulsion drug delivery systems |
US6479060B1 (en) | 2001-09-04 | 2002-11-12 | Healthpoint, Ltd. | Elegant hydrogenated castor oil ointments |
FR2829693B1 (en) | 2001-09-20 | 2004-02-27 | Oreal | FOAMING COSMETIC CREAM |
DE10147820A1 (en) | 2001-09-27 | 2003-04-10 | Beiersdorf Ag | Self-foaming, foam-like, post-foaming or foamable cosmetic or dermatological preparations containing waxes or lipids which are solid and / or semi-solid at room temperature |
US7931533B2 (en) | 2001-09-28 | 2011-04-26 | Igt | Game development architecture that decouples the game logic from the graphics logics |
JP2005508937A (en) | 2001-10-05 | 2005-04-07 | ザ ジェネラル ホスピタル コーポレーション | Methods and compositions for treating skin lesions |
US20030185839A1 (en) | 2001-10-05 | 2003-10-02 | Podolsky Daniel K. | Methods and compositions for treating dermal lesions |
US6649574B2 (en) | 2001-10-10 | 2003-11-18 | Exxonmobil Research And Engineering Company | Biodegradable non-toxic gear oil |
DE60230893D1 (en) | 2001-10-26 | 2009-03-05 | Taiyo Kagaku Kk | OILY FOAMABLE AEROSOL COMPOSITION |
US20030082120A1 (en) | 2001-10-26 | 2003-05-01 | Milstein Harold J. | Method for reducing systemic effects of aging, effects of aging on the skin, and incidence of skin damage from sun exposure using antibiotics of the tetracycline family |
US7255869B2 (en) | 2001-10-30 | 2007-08-14 | The Procter & Gamble Company | Anhydrous cosmetic compositions containing polyols |
DE10154324A1 (en) | 2001-11-06 | 2003-08-07 | Merz Pharma Gmbh & Co Kgaa | Topically applicable compositions with external active substance depot formation, their production and their use |
DE10155956A1 (en) | 2001-11-09 | 2003-05-22 | Beiersdorf Ag | Self-foaming, foam-like, post-foaming or foamable cosmetic or dermatological preparations |
EP1446090A2 (en) | 2001-11-13 | 2004-08-18 | The Procter & Gamble Company | Compositions containing enzymes stabilized with certain osmo-protectants and methods for using such compositions in personal care |
DE10155792A1 (en) | 2001-11-14 | 2003-05-22 | Beiersdorf Ag | Self-foaming, foam-like, post-foaming or foamable cosmetic or dermatological preparations containing siloxane elastomers |
US6955816B2 (en) | 2001-11-16 | 2005-10-18 | Klysz Beatrice M | Anti-aging skin care composition and uses thereof |
DE10159002A1 (en) | 2001-11-30 | 2003-06-18 | Clariant Gmbh | Use of multi-phase foaming agents from foam dispensers |
FR2833246B1 (en) | 2001-12-06 | 2005-06-24 | Beatrice France Touteau | DEVICE FOR SIMULTANEOUSLY ACTING TWO AEROSOLS CONTAINING TWO PRODUCTS TO BE MIXED AT THE TIME OF USE |
US6531118B1 (en) | 2001-12-11 | 2003-03-11 | Avon Products, Inc. | Topical compositions with a reversible photochromic ingredient |
EP1455697A4 (en) | 2001-12-20 | 2009-08-05 | Femmepharma Holding Co Inc | Vaginal delivery of drugs |
SE0104421D0 (en) | 2001-12-21 | 2001-12-21 | Ponsus Pharma Ab | New composition |
US20030118515A1 (en) | 2001-12-21 | 2003-06-26 | Robert Jew | Cosmetic composition containing carbon dioxide |
US6765001B2 (en) | 2001-12-21 | 2004-07-20 | Medicis Pharmaceutical Corporation | Compositions and methods for enhancing corticosteroid delivery |
US20030129259A1 (en) | 2001-12-28 | 2003-07-10 | Avon Products, Inc. | Topical lightening compostitions and methods of use |
JP4549625B2 (en) | 2002-01-05 | 2010-09-22 | 株式會社アモーレパシフィック | Finely emulsified particles containing ginseng saponin metabolites as active ingredients, a method for producing the same, and a cosmetic composition for preventing skin aging containing the same |
US7192601B2 (en) | 2002-01-18 | 2007-03-20 | Walker Edward B | Antimicrobial and sporicidal composition |
US6992049B2 (en) | 2002-01-31 | 2006-01-31 | Exxonmobil Research And Engineering Company | Lubricating oil compositions |
NZ517094A (en) | 2002-02-08 | 2005-03-24 | Advanced Animal Technology Ltd | Improvements in and relating to substance delivery device |
CN100396684C (en) | 2002-02-14 | 2008-06-25 | 基姆逊有限公司 | Aluminium and hexa methylene tetramine composite and application thereof |
US6589216B1 (en) | 2002-02-20 | 2003-07-08 | Abbott Research Group, Inc. | Vaginal douches, vaginal douche applicators and methods of vaginal douching |
US6682511B2 (en) | 2002-02-21 | 2004-01-27 | Robert Wallace Besoyan | Brief protector |
US7635463B2 (en) | 2002-02-27 | 2009-12-22 | Pharmain Corporation | Compositions for delivery of therapeutics and other materials |
US6691898B2 (en) | 2002-02-27 | 2004-02-17 | Fomo Products, Inc. | Push button foam dispensing device |
AU2003213787A1 (en) | 2002-03-06 | 2003-09-22 | Cellegy Pharmaceuticals, Inc. | Compositions and methods for the treatment of anorectal disorders |
US20050281766A1 (en) | 2002-03-11 | 2005-12-22 | Avon Products, Inc. | Method of improving the aesthetic appearance of epithelia |
US6736860B2 (en) | 2002-03-12 | 2004-05-18 | Unilever Home & Personal Care Usa Division Of Conopco, Inc. | Gradual permanent coloring of hair using dye intermediates dissolved in alkaline water with fatty alcohol |
CA2422244A1 (en) | 2002-03-14 | 2003-09-14 | Homax Products, Inc. | Aerosol systems and methods for mixing and dispensing two-part materials |
DE60333350D1 (en) | 2002-03-19 | 2010-08-26 | Airspray Int Bv | SUPPLY UNIT |
US20030180347A1 (en) | 2002-03-19 | 2003-09-25 | W.F. Young, Incorporated | Patch for the delivery of topical agents |
AU2003221093A1 (en) | 2002-03-28 | 2003-10-13 | Hakuto Co., Ltd. | Method of foam stabilization for foam cosmetic |
EP1496773B1 (en) | 2002-04-12 | 2006-08-30 | Dreamwell, Ltd. | Cassette bedding system |
US8192749B2 (en) | 2003-04-16 | 2012-06-05 | Galderma Laboratories Inc. | Methods of simultaneously treating ocular rosacea and acne rosacea |
US8846039B2 (en) | 2002-04-26 | 2014-09-30 | Asan Laboratories Company (Cayman), Limited | Method for ameliorating pruritus |
US6875438B2 (en) | 2002-04-27 | 2005-04-05 | Aventis Pharma Deutschland Gmbh | Preparations for topical administration of substances having antiandrogenic activity |
CA2384922C (en) | 2002-05-03 | 2008-09-02 | Purepharm Inc. | Topical glycopyrrolate product for the reduction of sweating |
CA2500134A1 (en) | 2002-05-06 | 2003-11-13 | Collagenex Pharmaceuticals, Inc. | Methods of simultaneously treating mucositis and fungal infection |
JP4108678B2 (en) | 2002-05-10 | 2008-06-25 | ユニリーバー・ナームローゼ・ベンノートシヤープ | Hair conditioning composition |
US6783027B2 (en) | 2002-05-15 | 2004-08-31 | The Procter & Gamble Company | Metered-dose underarm product and package |
US20030215472A1 (en) | 2002-05-16 | 2003-11-20 | Bonda Craig A | Methods and compositions employing a dialkyl amide |
KR20050007553A (en) | 2002-05-20 | 2005-01-19 | 콜라제넥스 파마슈티칼스, 인크 | Methods of treating allergic reactions |
JP4050094B2 (en) | 2002-05-28 | 2008-02-20 | 株式会社三谷バルブ | Metering valve mechanism and aerosol products |
US6723309B1 (en) | 2002-06-10 | 2004-04-20 | Jeffrey Alan Deane | Hair cleansing conditioner |
FR2840903B1 (en) | 2002-06-13 | 2005-01-28 | Oreal | GLUCOSE AND VITAMIN F DERIVATIVE, COMPOSITIONS COMPRISING THE SAME, AND USES FOR IMPROVING THE CONDITION OF HAIR AND HAIR |
US7763587B2 (en) | 2002-06-13 | 2010-07-27 | L'oreal S.A. | Derivative of glucose and of vitamin F, compositions comprising it, uses and preparation process |
US7163669B2 (en) | 2002-06-19 | 2007-01-16 | J.M. Huber Corporation | Cosmetic compositions comprising calcium silicates |
ATE490932T1 (en) | 2002-06-26 | 2010-12-15 | Daizo Co Ltd | PACKAGING CONTAINER FOR DISCHARGING MULTIPLE CONTENTS, PACKAGING PRODUCT WITH THE PACKAGING CONTAINER AND METHOD FOR PRODUCING THE PACKAGING PRODUCT |
JP2004026605A (en) | 2002-06-27 | 2004-01-29 | Asahi Fiber Glass Co Ltd | Greige goods for glass fiber yarn and glass fiber yarn made using this |
US20040002550A1 (en) | 2002-06-28 | 2004-01-01 | Mercurio Anthony Fred | Post foaming compositions |
US6785629B2 (en) | 2002-07-02 | 2004-08-31 | Agilent Technologies, Inc. | Accuracy determination in bit line voltage measurements |
JP3833972B2 (en) | 2002-07-08 | 2006-10-18 | 古河電気工業株式会社 | Wire harness assembly system |
DE10233330B4 (en) | 2002-07-22 | 2007-04-26 | Sasol Germany Gmbh | Microemulsion containing UV photoprotective filter and / or anti-dandruff agent |
US7137536B2 (en) | 2002-07-22 | 2006-11-21 | Seaquist Perfect Dispensing Foreign, Inc. | Inverted aerosol dispenser |
US6897195B2 (en) | 2002-07-24 | 2005-05-24 | Nanjing Zhongshi Chemical Co. | Composition of menthol and menthyl lactate, its preparation method and its applications as a cooling agent |
US20020182162A1 (en) | 2002-08-07 | 2002-12-05 | Mohsen Shahinpoor | Nitric oxide (NO) donor+cGMP-PDE5 inhibitor as a topical drug for enhanced hair growth |
FR2843373B1 (en) | 2002-08-12 | 2005-03-04 | Jean Augustin | DEVICE FOR PACKAGING AND APPLYING A PRODUCT IN FLUID FORM |
US7939170B2 (en) | 2002-08-15 | 2011-05-10 | The Rockefeller University | Water soluble metal and semiconductor nanoparticle complexes |
DE60323380D1 (en) | 2002-08-26 | 2008-10-16 | Sla Pharma Ag | TOPICAL FORMULATION WITH AT LEAST 10% METRONIDAZOLE IN DECORATED PETROLATE AND THEIR USE IN ANAL AND RECTIFIC AREAS |
US6770607B2 (en) | 2002-09-12 | 2004-08-03 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Viscoelastic cleansing gel with micellar surfactant solutions |
US7906473B2 (en) | 2002-09-13 | 2011-03-15 | Bissell Homecare, Inc. | Manual spray cleaner |
GB0221697D0 (en) | 2002-09-18 | 2002-10-30 | Unilever Plc | Novel compouds and their uses |
US6968982B1 (en) | 2002-09-18 | 2005-11-29 | Burns Caleb E S | Multiple-mist dispenser |
US7179481B2 (en) | 2002-09-19 | 2007-02-20 | Kimberly-Clark Worldwide, Inc. | Vaginal health products |
US6949037B2 (en) | 2002-09-27 | 2005-09-27 | Richard A. Enos | Quick-release fastener for releasably attaching lacrosse stick head to shaft |
DE60324641D1 (en) | 2002-09-30 | 2008-12-24 | Kao Corp | Foamable emulsion of the oil-in-water type |
FR2845672B1 (en) | 2002-10-09 | 2006-02-10 | Airlessystems | FLUID PRODUCT DISPENSER |
EP1567113A4 (en) | 2002-10-24 | 2006-11-08 | G & R Pharmaceuticals Llc | Antifungal formulations |
IL152486A0 (en) | 2002-10-25 | 2003-05-29 | Meir Eini | Alcohol-free cosmetic and pharmaceutical foam carrier |
US8900554B2 (en) | 2002-10-25 | 2014-12-02 | Foamix Pharmaceuticals Ltd. | Foamable composition and uses thereof |
US7700076B2 (en) | 2002-10-25 | 2010-04-20 | Foamix, Ltd. | Penetrating pharmaceutical foam |
US10117812B2 (en) | 2002-10-25 | 2018-11-06 | Foamix Pharmaceuticals Ltd. | Foamable composition combining a polar solvent and a hydrophobic carrier |
US20060018937A1 (en) | 2002-10-25 | 2006-01-26 | Foamix Ltd. | Steroid kit and foamable composition and uses thereof |
US9668972B2 (en) | 2002-10-25 | 2017-06-06 | Foamix Pharmaceuticals Ltd. | Nonsteroidal immunomodulating kit and composition and uses thereof |
US20080206161A1 (en) | 2002-10-25 | 2008-08-28 | Dov Tamarkin | Quiescent foamable compositions, steroids, kits and uses thereof |
US9265725B2 (en) | 2002-10-25 | 2016-02-23 | Foamix Pharmaceuticals Ltd. | Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof |
US20050186142A1 (en) | 2002-10-25 | 2005-08-25 | Foamix Ltd. | Kit and composition of imidazole with enhanced bioavailability |
US20070292359A1 (en) | 2002-10-25 | 2007-12-20 | Foamix Ltd. | Polypropylene glycol foamable vehicle and pharmaceutical compositions thereof |
US8119109B2 (en) | 2002-10-25 | 2012-02-21 | Foamix Ltd. | Foamable compositions, kits and methods for hyperhidrosis |
US9211259B2 (en) | 2002-11-29 | 2015-12-15 | Foamix Pharmaceuticals Ltd. | Antibiotic kit and composition and uses thereof |
AU2003279493B2 (en) | 2002-10-25 | 2009-08-20 | Foamix Pharmaceuticals Ltd. | Cosmetic and pharmaceutical foam |
US20080317679A1 (en) | 2002-10-25 | 2008-12-25 | Foamix Ltd. | Foamable compositions and kits comprising one or more of a channel agent, a cholinergic agent, a nitric oxide donor, and related agents and their uses |
US7704518B2 (en) | 2003-08-04 | 2010-04-27 | Foamix, Ltd. | Foamable vehicle and pharmaceutical compositions thereof |
US20060233721A1 (en) | 2002-10-25 | 2006-10-19 | Foamix Ltd. | Foam containing unique oil globules |
US20080031907A1 (en) | 2002-10-25 | 2008-02-07 | Foamix Ltd. | Cosmetic and pharmaceutical foam |
US8119150B2 (en) | 2002-10-25 | 2012-02-21 | Foamix Ltd. | Non-flammable insecticide composition and uses thereof |
US7820145B2 (en) | 2003-08-04 | 2010-10-26 | Foamix Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US8486376B2 (en) | 2002-10-25 | 2013-07-16 | Foamix Ltd. | Moisturizing foam containing lanolin |
US20050205086A1 (en) | 2002-10-25 | 2005-09-22 | Foamix Ltd. | Retinoid immunomodulating kit and composition and uses thereof |
US20070292461A1 (en) | 2003-08-04 | 2007-12-20 | Foamix Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US20120156144A1 (en) | 2002-10-25 | 2012-06-21 | Foamix | Foamable Compositions, Kits and Methods for Hyperhidrosis |
US20070292355A1 (en) | 2002-10-25 | 2007-12-20 | Foamix Ltd. | Anti-infection augmentation foamable compositions and kit and uses thereof |
US20160158261A1 (en) | 2002-10-25 | 2016-06-09 | Foamix Pharmaceuticals Ltd. | Antibiotic Kit and Composition and Uses Thereof |
US20080138296A1 (en) | 2002-10-25 | 2008-06-12 | Foamix Ltd. | Foam prepared from nanoemulsions and uses |
US20050271596A1 (en) | 2002-10-25 | 2005-12-08 | Foamix Ltd. | Vasoactive kit and composition and uses thereof |
US20060193789A1 (en) | 2002-10-25 | 2006-08-31 | Foamix Ltd. | Film forming foamable composition |
EP1556332B1 (en) | 2002-10-28 | 2016-10-05 | Givaudan SA | Coolant solutions and compositions comprising the same |
JP2004250435A (en) | 2002-11-21 | 2004-09-09 | Dai Ichi Seiyaku Co Ltd | Composition for hair growth |
JP4282311B2 (en) | 2002-11-26 | 2009-06-17 | 三洋電機株式会社 | Ice making equipment |
WO2004052317A1 (en) | 2002-12-12 | 2004-06-24 | Neubourg Skin Care Gmbh & Co. Kg | Stable foam cream |
GB0229071D0 (en) | 2002-12-13 | 2003-01-15 | Unilever Plc | Cosmetic method and composition for enhancing attractiveness |
US20040191196A1 (en) | 2002-12-16 | 2004-09-30 | Dov Tamarkin | Novel conjugate compounds and dermatological compositions thereof |
FR2848847B1 (en) | 2002-12-18 | 2005-10-14 | Coletica | COSMETIC OR DERMOPHARMACEUTICAL COMPOSITION COMPRISING AN AQUEOUS INSOLUBLE ENZYME AND USES THEREOF |
US7842791B2 (en) | 2002-12-19 | 2010-11-30 | Nancy Jean Britten | Dispersible pharmaceutical compositions |
FR2848998B1 (en) | 2002-12-20 | 2006-04-07 | Oreal | DISPENSING DEVICE HAVING MEANS FOR DISTRIBUTING TWO PRODUCTS IN VARIABLE PROPORTIONS |
JP2006515026A (en) | 2003-01-02 | 2006-05-18 | フェムファーマ ホールディング カンパニー, インコーポレイテッド | Pharmaceutical preparations for the treatment of breast diseases and disorders |
WO2004064769A2 (en) | 2003-01-21 | 2004-08-05 | Hector Herrera | Methods for making and using topical delivery agents |
JP4828404B2 (en) | 2003-01-24 | 2011-11-30 | ステフェル リサーチ オーストラリア プロプライエタリー リミティッド | Clindamycin phosphate foam |
US20040151756A1 (en) | 2003-02-04 | 2004-08-05 | Richards Anthony P. | Edible low density high surface area drug vehicle, method of manufacturing low density high surface area drug vehicle |
EP1603560A1 (en) | 2003-02-06 | 2005-12-14 | Cipla Ltd. | Topical immunotherapy and compositions for use therein |
JP2006514700A (en) | 2003-02-12 | 2006-05-11 | コネティックス オーストラリア ピーティーワイ リミテッド | Film-forming hydroalcoholic foam |
US6841547B2 (en) | 2003-02-28 | 2005-01-11 | Albert Einstein College Of Medicine Of Yeshevia University | Method for decreasing low density lipoprotein |
US20040175347A1 (en) | 2003-03-04 | 2004-09-09 | The Procter & Gamble Company | Regulation of mammalian keratinous tissue using hexamidine compositions |
GB0305010D0 (en) | 2003-03-05 | 2003-04-09 | Unilever Plc | Changing colours |
US6843390B1 (en) | 2003-03-17 | 2005-01-18 | Joe G. Bristor | Multiple fluid closed system dispensing device |
US7357950B2 (en) | 2003-03-21 | 2008-04-15 | Elizabeth Anne Mazzio | Topical treatment for dyshidrosis (pompholyx) and dry skin disorders |
US20040192754A1 (en) | 2003-03-24 | 2004-09-30 | Shapira Nathan Andrew | Methods for treating idiopathic hyperhidrosis and associated conditions |
WO2004084973A2 (en) | 2003-03-24 | 2004-10-07 | Becton, Dickinson And Company | Invisible antimicrobial glove and hand antiseptic |
DE10315936A1 (en) | 2003-04-03 | 2004-10-28 | Ing. Erich Pfeiffer Gmbh | Discharge device for at least one medium |
GB0308585D0 (en) | 2003-04-14 | 2003-05-21 | Pz Cussons Int Ltd | Cleaning composition |
US20040220187A1 (en) | 2003-04-22 | 2004-11-04 | Pharmacia Corporation | Compositions of a cyclooxygenase-2 selective inhibitor and a sodium ion channel blocker for the treatment of pain, inflammation or inflammation mediated disorders |
US20040229803A1 (en) | 2003-04-22 | 2004-11-18 | Pharmacia Corporation | Compositions of a cyclooxygenase-2 selective inhibitor and a potassium ion channel modulator for the treatment of pain, inflammation or inflammation mediated disorders |
US7575739B2 (en) | 2003-04-28 | 2009-08-18 | Foamix Ltd. | Foamable iodine composition |
DE10319771B4 (en) | 2003-05-02 | 2005-03-17 | Koenig & Bauer Ag | System for inspecting a printed image |
JP2004353084A (en) | 2003-05-08 | 2004-12-16 | Sanyo Electric Co Ltd | Evaporator fixation member |
FR2854821B1 (en) | 2003-05-16 | 2006-12-08 | Oreal | ASSEMBLY FOR PACKAGING AND DISPENSING A PRODUCT, IN PARTICULAR IN THE FORM OF A SAMPLE |
JP4232535B2 (en) | 2003-05-20 | 2009-03-04 | セイコーエプソン株式会社 | Printer maintenance system, print control server, client, method related thereto and program related thereto |
US7222802B2 (en) | 2003-05-23 | 2007-05-29 | Meadwestvaco Corporation | Dual sprayer with external mixing chamber |
US7648711B2 (en) | 2003-05-25 | 2010-01-19 | Yuwan Wang | Dimethicone-containing sustained release injection formulation |
US7186416B2 (en) | 2003-05-28 | 2007-03-06 | Stiefel Laboratories, Inc. | Foamable pharmaceutical compositions and methods for treating a disorder |
WO2004105722A1 (en) | 2003-05-30 | 2004-12-09 | Gianfranco De Paoli Ambrosi | A formulation for chemical peeling |
US20050079228A1 (en) | 2003-05-30 | 2005-04-14 | Ashish Jaiswal | Clear, stable topical compositions of clarithromycin and processes for their preparation |
US20050208083A1 (en) | 2003-06-04 | 2005-09-22 | Nanobio Corporation | Compositions for inactivating pathogenic microorganisms, methods of making the compositons, and methods of use thereof |
JP4018032B2 (en) | 2003-06-17 | 2007-12-05 | 高砂香料工業株式会社 | Hair and body cleaning composition |
CA2524739A1 (en) | 2003-06-18 | 2004-12-29 | Galderma S.A. | Metronidazole-based green tinted topical pharmaceutical composition |
CA2528344A1 (en) | 2003-06-19 | 2004-12-29 | The Procter & Gamble Company | Polyol-in-silicone emulsions |
US20050042182A1 (en) | 2003-08-13 | 2005-02-24 | Moshe Arkin | Topical compositions of urea |
EP1642592A4 (en) | 2003-07-03 | 2007-02-07 | Japan Science & Tech Corp | Remedy for sarcoidosis and method of treating the same |
US20070140999A1 (en) | 2003-07-18 | 2007-06-21 | Hill Dermaceuticals, Inc. | Topical skin care composition containing refined peanut oil |
EP1653932A1 (en) | 2003-07-24 | 2006-05-10 | Ranbaxy Laboratories Limited | Modified release compositions for minocycline |
US7226230B2 (en) | 2003-07-28 | 2007-06-05 | Raymond Liberatore | Spreader |
WO2005011567A2 (en) | 2003-08-04 | 2005-02-10 | Foamix Ltd. | Foam carrier containing amphiphilic copolymeric gelling agent |
US8795693B2 (en) * | 2003-08-04 | 2014-08-05 | Foamix Ltd. | Compositions with modulating agents |
US20080069779A1 (en) | 2003-08-04 | 2008-03-20 | Foamix Ltd. | Foamable vehicle and vitamin and flavonoid pharmaceutical compositions thereof |
US8486374B2 (en) | 2003-08-04 | 2013-07-16 | Foamix Ltd. | Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses |
KR20060113657A (en) | 2003-08-25 | 2006-11-02 | 포믹스 리미티드 | Penetrating pharmaceutical foam |
US20060140990A1 (en) | 2003-09-19 | 2006-06-29 | Drugtech Corporation | Composition for topical treatment of mixed vaginal infections |
CN1886126A (en) | 2003-09-25 | 2006-12-27 | Dmi生物科学公司 | Methods and products which utilize N-acyl-L-aspartic acid |
FR2860143B1 (en) | 2003-09-26 | 2008-06-27 | Oreal | COSMETIC COMPOSITION COMPRISING A SEQUENCE POLYMER AND A NON-VOLATILE SILICONE OIL |
US20050084551A1 (en) | 2003-09-26 | 2005-04-21 | Jensen Claude J. | Morinda citrifolia-based oral care compositions and methods |
PL3428257T3 (en) | 2003-09-29 | 2023-11-20 | Deb Ip Limited | High alcohol content gel-like and foaming compositions |
GB2406330B (en) | 2003-09-29 | 2005-12-07 | Bespak Plc | A dispensing apparatus |
CA2528818C (en) | 2003-10-03 | 2010-08-10 | Collegium Pharmaceutical, Inc. | Topical aerosol foams |
FR2860502B1 (en) | 2003-10-07 | 2007-09-14 | Valois Sas | DOSING VALVE AND DEVICE FOR DISPENSING FLUID PRODUCT COMPRISING SUCH A VALVE |
GB0323908D0 (en) | 2003-10-11 | 2003-11-12 | Nupharm Lab Ltd | Pharmaceutical foam formulation |
WO2005034903A1 (en) | 2003-10-14 | 2005-04-21 | Showa Denko K.K. | Agent for skin external use containing salt of ascorbic acid derivative, method for stabilizing the agent for skin external use, and stabilizer |
FR2860976B1 (en) | 2003-10-20 | 2006-02-10 | Ravi Shrivastava | NOVEL SYNERGISTIC COMPOSITIONS FOR IMPROVING THE BIODAVAILABILITY AND EFFICIENCY OF POLYUNSATURATED FATTY ACIDS FOR THE TREATMENT OF BRAIN FUNCTIONING DISORDERS. |
US7419498B2 (en) | 2003-10-21 | 2008-09-02 | Nmt Medical, Inc. | Quick release knot attachment system |
WO2005044219A1 (en) | 2003-10-31 | 2005-05-19 | The Procter & Gamble Company | Skin care composition containing dehydroacetic acid and skin care actives |
NZ547628A (en) | 2003-11-06 | 2010-07-30 | Univ New York State Res Found | Methods of treating eczema |
US8157788B2 (en) | 2003-11-06 | 2012-04-17 | Paolo L. Manfredi | Multi-site drug delivery platform |
MXPA06004593A (en) | 2003-11-06 | 2006-06-27 | Unilever Nv | Improved cosmetic composition comprising vitamin b3, vitamin b6 and an organic acid. |
DE10354051A1 (en) | 2003-11-17 | 2005-06-16 | Beiersdorf Ag | Dispensers containing cosmetic preparations containing aids for keeping the donor in motion |
EP1694283A1 (en) | 2003-11-17 | 2006-08-30 | The Procter & Gamble Company | Antiperspirant composition and applicator therefor |
AU2004290982B2 (en) | 2003-11-21 | 2008-06-19 | Pfizer Products Inc. | The use of anti biotics as vaccine adjuvants |
US20050115988A1 (en) | 2003-12-01 | 2005-06-02 | Brian Law | Multiple liquid foamer |
US20050123496A1 (en) | 2003-12-08 | 2005-06-09 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Self foaming non-aqueous personal wash cleansers with little or no surfactant |
DE10361022A1 (en) | 2003-12-23 | 2005-07-28 | Merckle Gmbh Chem.-Pharm. Fabrik | Topical preparations containing dimethyl sulfoxide and dexpanthenol |
PL2204374T3 (en) | 2003-12-30 | 2012-11-30 | Gilead Sciences Inc | Nucleoside phosphonates and analogs thereof for the treatment of HPV-infections |
IL159729A0 (en) | 2004-01-06 | 2004-06-20 | Doron I Friedman | Non-aqueous composition for oral delivery of insoluble bioactive agents |
US20050186147A1 (en) | 2004-02-04 | 2005-08-25 | Foamix Ltd. | Cosmetic and pharmaceutical foam with solid matter |
US7225518B2 (en) | 2004-02-23 | 2007-06-05 | Boston Scientific Scimed, Inc. | Apparatus for crimping a stent assembly |
JP4381169B2 (en) | 2004-02-27 | 2009-12-09 | 花王株式会社 | Hair cosmetics |
SG150568A1 (en) | 2004-03-03 | 2009-03-30 | Revance Therapeutics Inc | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
WO2005089582A2 (en) | 2004-03-18 | 2005-09-29 | Bodypoint Designs, Inc. | Pivoting side mount and quick release assembly for a pelvic stabilization device |
DE102004016710B4 (en) | 2004-04-05 | 2020-11-19 | Greppmayr GmbH | Foot care formulation |
DK1734927T3 (en) | 2004-04-08 | 2012-09-24 | Meda Pharma S A R L | Pimecrolimus foam composition containing hexylene glycol, optionally oleyl alcohol, dimethyl isosorbide and / or medium chain triglycerides |
ES2429443T3 (en) | 2004-04-19 | 2013-11-14 | Strategic Science & Technologies, Llc | Transdermal supply of beneficial substances by means of an environment of high ionic strength |
NL1026031C2 (en) | 2004-04-23 | 2005-10-25 | Airspray Nv | Delivery assembly. |
EP1768648A1 (en) | 2004-04-28 | 2007-04-04 | Foamix Ltd. | Body cavity foams |
JP2005314323A (en) | 2004-04-30 | 2005-11-10 | Sato Pharmaceutical Co Ltd | Hair growth formulation |
US20050244354A1 (en) | 2004-04-30 | 2005-11-03 | Sam Speron | Oxygenated personal care products |
WO2005115336A2 (en) | 2004-05-15 | 2005-12-08 | Collegium Pharmaceutical, Inc. | Sprayable formulations for the treatment of acute inflammatory skin conditions |
US7083125B2 (en) | 2004-05-17 | 2006-08-01 | S.C. Johnson & Son, Inc. | Detachable tube assembly |
US7143909B2 (en) | 2004-05-21 | 2006-12-05 | Sonoco Development, Inc. | Reconfigurable metered material dispenser |
WO2005117813A1 (en) | 2004-05-26 | 2005-12-15 | L'oreal | Cosmetic mousse formulations |
ITBO20040338A1 (en) | 2004-05-28 | 2004-08-28 | Progine Farmaceutici Srl | VAGINAL NEBULIZATION DISPENSER |
US20050268416A1 (en) | 2004-06-03 | 2005-12-08 | Sommers J E | Foldable lotion applicator |
JP4368250B2 (en) | 2004-06-09 | 2009-11-18 | ポーラ化成工業株式会社 | Post-form dosage form of warm cosmetic |
FR2871698B1 (en) | 2004-06-17 | 2008-07-04 | Galderma Sa | SPRAY COMPOSITION COMPRISING AN ASSOCIATION OF PHARMACEUTICAL ASSETS AND AN OILY PHASE |
FR2871696B1 (en) | 2004-06-17 | 2006-11-10 | Galderma Sa | TOPICAL COMPOSITION FOR THE TREATMENT OF PSORIASIS |
US8211449B2 (en) | 2004-06-24 | 2012-07-03 | Dpt Laboratories, Ltd. | Pharmaceutically elegant, topical anhydrous aerosol foam |
JP4355264B2 (en) | 2004-06-25 | 2009-10-28 | ポーラ化成工業株式会社 | Warm feeling non-water foam cosmetic |
US7207655B2 (en) | 2004-06-28 | 2007-04-24 | Eastman Kodak Company | Latency stirring in fluid ejection mechanisms |
US6991789B2 (en) | 2004-06-29 | 2006-01-31 | Allergas, Inc. | Methods of modulating intracellular degradation rates of toxins |
US20060008432A1 (en) | 2004-07-07 | 2006-01-12 | Sebastiano Scarampi | Gilsonite derived pharmaceutical delivery compositions and methods: nail applications |
UA93354C2 (en) | 2004-07-09 | 2011-02-10 | Гилиад Сайенсиз, Инк. | Topical antiviral formulations |
US20060121073A1 (en) | 2004-07-12 | 2006-06-08 | Sandhya Goyal | Topical gel formulation comprising insecticide and its preparation thereof |
MXPA06014390A (en) | 2004-07-19 | 2007-10-02 | Warner Lambert Co | Formulation for stimulating hair growth. |
WO2006010589A2 (en) | 2004-07-29 | 2006-02-02 | Mipharm S.P.A. | Post foaming gel mousse |
JP4557624B2 (en) | 2004-07-29 | 2010-10-06 | 株式会社吉野工業所 | Quantitative dispenser |
US20060029565A1 (en) | 2004-08-09 | 2006-02-09 | The Gillette Company | Self-heating shave foam product |
US7734193B2 (en) | 2004-08-12 | 2010-06-08 | Tri Quint Semiconductor, Inc. | Level detector for optical receivers |
TWI397427B (en) | 2004-08-31 | 2013-06-01 | Stiefel Res Australia Pty Ltd | Micro emulsion and sub-micron emulsion process and composition |
KR100623013B1 (en) | 2004-09-04 | 2006-09-19 | 김영대 | Nano-emulsion, the use thereof, and preparing method thereof |
PT1809303T (en) | 2004-09-23 | 2019-06-17 | Arc Medical Devices Inc | Pharmaceutical compositions and methods relating to inhibiting fibrous adhesions or inflammatory disease using low sulphate fucans |
DK1791791T3 (en) | 2004-09-27 | 2019-08-26 | Special Water Patents B V | Methods and compositions for treating water |
FR2875797B1 (en) | 2004-09-30 | 2006-11-24 | Oreal | DISTRIBUTION ASSEMBLY FOR THE EXTENDED DISTRIBUTION OF TWO PRODUCTS |
BRPI0404595A (en) | 2004-10-26 | 2006-06-13 | Natura Cosmeticos Sa | oil-in-water nanoemulsion, cosmetic composition and cosmetic product comprising same, process for preparing said nanoemulsion |
DE102004052986A1 (en) | 2004-11-02 | 2006-05-04 | Lindal Ventil Gmbh | Device for mixing two different components |
US7350673B2 (en) | 2004-11-19 | 2008-04-01 | Glynntech, Inc. | Metered dose squeeze dispenser |
US20060110415A1 (en) | 2004-11-22 | 2006-05-25 | Bioderm Research | Topical Delivery System for Cosmetic and Pharmaceutical Agents |
US8080560B2 (en) | 2004-12-17 | 2011-12-20 | 3M Innovative Properties Company | Immune response modifier formulations containing oleic acid and methods |
FR2880802B1 (en) | 2005-01-14 | 2008-12-19 | Sederma Soc Par Actions Simpli | COSMETIC OR DERMOPHARMACEUTICAL COMPOSITION CONTAINING EUGLENE EXTRACT |
WO2006081327A2 (en) | 2005-01-25 | 2006-08-03 | University Of Vermont And State Agricultural College | Small molecules that reduce fungal growth |
CA2595692A1 (en) | 2005-01-28 | 2006-08-03 | Basf Aktiengesellschaft | Use of a water-in-water emulsion polymers in the form of a thickener for cosmetic preparations |
US20060177392A1 (en) | 2005-02-10 | 2006-08-10 | William Walden | Oil-based composition for acne |
US20060193813A1 (en) | 2005-02-11 | 2006-08-31 | L'oreal | Nanoemulsion containing a hydroxylated urea compound |
GB0506141D0 (en) | 2005-03-24 | 2005-05-04 | Transphase Ltd | A topical compostion and its uses |
US20090061001A1 (en) | 2005-03-24 | 2009-03-05 | Ensign Laboratories Pty Ltd | Sunscreen aerosol spray |
US20060222675A1 (en) | 2005-03-29 | 2006-10-05 | Sabnis Ram W | Personal care compositions with color changing indicator |
US20070069046A1 (en) | 2005-04-19 | 2007-03-29 | Foamix Ltd. | Apparatus and method for releasing a measure of content from a plurality of containers |
WO2008020268A2 (en) | 2005-04-19 | 2008-02-21 | Foamix Ltd. | Apparatus and method for releasing a measured amount of content from a container |
BRPI0613548A2 (en) | 2005-05-05 | 2011-01-18 | Genencor Int | personal care compositions and methods for their use |
WO2007054818A2 (en) | 2005-05-09 | 2007-05-18 | Foamix Ltd. | Foamable vehicle and pharmaceutical compositions thereof |
DK1879595T3 (en) | 2005-05-10 | 2015-01-05 | Dermipsor Ltd | Preparations and Methods for the Treatment of Hyperproliferative Epidermal Diseases |
WO2006122158A2 (en) | 2005-05-10 | 2006-11-16 | Xanthone Plus International, Llc | Skin care compositions containing xanthones |
US20060260655A1 (en) * | 2005-05-23 | 2006-11-23 | Martin William R | Asbestos removal process |
EP1917072B1 (en) | 2005-06-01 | 2013-02-27 | Stiefel Research Australia Pty Ltd | Vitamin formulation |
US20060272199A1 (en) | 2005-06-02 | 2006-12-07 | Bmc Manufacturing, Llc | Aqueous gel candle for use with a warming device |
US8211874B2 (en) | 2005-06-03 | 2012-07-03 | Galderma Laboratories Inc. | Inhibition of thrombin generation |
WO2007099396A2 (en) | 2005-06-07 | 2007-09-07 | Foamix Ltd. | Antibiotic kit and composition and uses thereof |
WO2007085899A2 (en) | 2005-07-06 | 2007-08-02 | Foamix Ltd. | Foamable arthropocidal composition for tropical application |
US20070009607A1 (en) | 2005-07-11 | 2007-01-11 | George Jones | Antibacterial/anti-infalmmatory composition and method |
US20070015738A1 (en) | 2005-07-15 | 2007-01-18 | Walker Stephen G | Use of non-antibacterial tetracycline formulations for inhibiting bacterial spores from becoming infectious vegetative cells |
EP1752128B1 (en) | 2005-07-18 | 2015-01-14 | Wella GmbH | Aerosol creme mousse, method of treating hair and use |
WO2007085902A2 (en) | 2005-07-19 | 2007-08-02 | Foamix Ltd. | Foamable composition combining a polar solvent and a hydrophobic carrier |
US20080152596A1 (en) | 2005-07-19 | 2008-06-26 | Foamix Ltd. | Polypropylene glycol foamable vehicle and pharmaceutical compositions thereof |
CN100531515C (en) | 2005-07-22 | 2009-08-19 | 鸿富锦精密工业(深圳)有限公司 | Printing circuit board with modified power zone block |
DE602005010417D1 (en) | 2005-07-22 | 2008-11-27 | Wella Ag | Hair treatment method with a dry foam used as a mechanical vehicle |
DE102005037844A1 (en) | 2005-08-04 | 2007-04-05 | Intendis Gmbh | Anhydrous multi-phase gel system |
JP2009504805A (en) | 2005-08-09 | 2009-02-05 | ナノバイオ コーポレーション | Nanoemulsion composition having anti-inflammatory activity |
EP1933941A2 (en) | 2005-08-25 | 2008-06-25 | Philip R. Houle | Treatment systems for delivery of sensitizer solutions |
FR2890559B1 (en) | 2005-09-13 | 2011-06-24 | Galderma Sa | DERMATOLOGICAL FOAMS BASED ON METRONIDAZOLE AND EMULSIONS FOR PREPARATION |
DE202006004676U1 (en) | 2005-09-28 | 2007-02-08 | Neubourg Skin Care Gmbh & Co. Kg | Formulation, useful as foam skin cream and to treat e.g. dermatitis and psoriasis, comprises an aqueous emulsion, propellant gas, urea emulsion, hyaluronic acid, free fatty acid and at least two emulsions |
EP1948130B1 (en) | 2005-10-24 | 2013-09-11 | Precision Dermatology, Inc. | Topical pharmaceutical foam composition |
US20070134174A1 (en) | 2005-11-03 | 2007-06-14 | Christopher Irwin | Personal care composition |
JP2007131539A (en) | 2005-11-08 | 2007-05-31 | Koike Kagaku Kk | Chilling foam cosmetic |
US20070148194A1 (en) | 2005-11-29 | 2007-06-28 | Amiji Mansoor M | Novel nanoemulsion formulations |
JP4885529B2 (en) | 2005-12-08 | 2012-02-29 | 住友重機械工業株式会社 | Radiation detection unit and radiation inspection apparatus |
US20070160548A1 (en) | 2005-12-13 | 2007-07-12 | Playtex Products, Inc. | Moisturizing sunless tanning composition |
US20070142263A1 (en) | 2005-12-15 | 2007-06-21 | Stahl Katherine D | Color changing cleansing composition |
US20070148112A1 (en) | 2005-12-28 | 2007-06-28 | Avon Products, Inc. | Foaming, color-changing topical composition and method of imparting a cosmetic effect |
AU2007207116B2 (en) | 2006-01-19 | 2012-08-02 | Disphar International B.V. | Foam-forming composition |
US20070166273A1 (en) | 2006-01-19 | 2007-07-19 | Krivulka Joseph J | Skin treatment educational kit |
WO2007103555A2 (en) | 2006-03-08 | 2007-09-13 | Nuviance, Inc. | Transdermal drug delivery compositions and topical compositions for application on the skin |
US20070224143A1 (en) | 2006-03-21 | 2007-09-27 | Kamedis Ltd. | Cosmetic and pharmaceutical foam carrier |
EP1996146B1 (en) | 2006-03-22 | 2014-04-30 | The Procter and Gamble Company | Aerosol product comprising a foaming concentrate composition comprising particulate materials |
US7252816B1 (en) | 2006-03-29 | 2007-08-07 | Dow Pharmaceutical Sciences | Topical acne vulgairs medication with a sunscreen |
EP2010133B1 (en) | 2006-03-31 | 2016-05-04 | Stiefel Research Australia Pty Ltd | Foamable suspension gel |
WO2008075207A2 (en) | 2006-04-04 | 2008-06-26 | Foamix Ltd. | Anti-infection augmentation foamable compositions and kit and uses thereof |
US20070264317A1 (en) | 2006-05-15 | 2007-11-15 | Perrigo Israel Pharmaceuticals Ltd. | Imiquimod cream formulation |
RU2008152101A (en) | 2006-05-31 | 2010-07-10 | Дзе Дайл Корпорейшн (Us) | Alcohol-Containing Antimicrobial Compositions with Increased Efficiency |
JP4892282B2 (en) | 2006-06-09 | 2012-03-07 | アルプス電気株式会社 | Lubricating composition for electrical contacts |
WO2008110872A2 (en) | 2006-06-23 | 2008-09-18 | Foamix Ltd. | Foamable compositions and kits comprising one or more of a channel agent, a cholinergic agent, a nitric oxide donor, and related agents and their uses |
US7826675B2 (en) | 2006-07-04 | 2010-11-02 | Hewlett-Packard Development Company, L.P. | Feature-aware image defect removal |
ES2530390T3 (en) | 2006-07-05 | 2015-03-02 | Foamix Pharmaceuticals Ltd | Foaming vehicle of carboxylic acid and pharmaceutical compositions thereof |
CA2659095C (en) | 2006-07-14 | 2015-04-28 | Stiefel Research Australia Pty Ltd | Fatty acid pharmaceutical foam |
JP2009543866A (en) | 2006-07-18 | 2009-12-10 | ウイラ アイピー プロプライエタリー リミテッド | Immune response modifier |
US20080031908A1 (en) | 2006-07-25 | 2008-02-07 | L'oreal | Oily cosmetic composition in aerosol form |
JP2008040899A (en) | 2006-08-08 | 2008-02-21 | Fuji Xerox Co Ltd | Printing controller, program, and method |
MX2009002536A (en) | 2006-09-08 | 2009-04-14 | Foamix Ltd | Colored or colorable foamable composition and foam. |
ES2315123B1 (en) | 2006-09-25 | 2009-12-30 | Divasa-Farmavic, S.A. | STABLE PHARMACEUTICAL COMPOSITIONS OF TETRACICLINES IN SOLUTION, PROCEDURE FOR OBTAINING AND USES. |
HUP0600765A2 (en) | 2006-10-06 | 2008-10-28 | Istvan Piller | Container for stable carbondioxide foam, process for producing stable carbondioxide foam and method for using of foam |
WO2009007785A2 (en) | 2006-11-14 | 2009-01-15 | Foamix Ltd. | Stable non-alcoholic foamable pharmaceutical emulsion compositions with an unctuous emollient and their uses |
US20080260655A1 (en) | 2006-11-14 | 2008-10-23 | Dov Tamarkin | Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses |
EP2097065A2 (en) | 2006-11-29 | 2009-09-09 | Foamix Ltd. | Foamable waterless compositions with modulating agents |
JP2010513289A (en) | 2006-12-15 | 2010-04-30 | ザ プロクター アンド ギャンブル カンパニー | Skin care composition |
EP2104489A2 (en) | 2006-12-26 | 2009-09-30 | FemmePharma Holding Company, Inc. | Topical administration of danazol |
US20080292560A1 (en) | 2007-01-12 | 2008-11-27 | Dov Tamarkin | Silicone in glycol pharmaceutical and cosmetic compositions with accommodating agent |
WO2008087148A2 (en) | 2007-01-16 | 2008-07-24 | Oystershell N.V. | Foamable composition for killing arthropods and uses thereof |
US20080188445A1 (en) * | 2007-02-02 | 2008-08-07 | Warner Chilcott Company Inc. | Tetracycline compositions for topical administration |
WO2008097851A1 (en) * | 2007-02-02 | 2008-08-14 | Warner Chilcott Company, Inc. | Tetracycline compositions for topical administration |
PT103661B (en) | 2007-02-23 | 2010-09-07 | Hovione Farmaciencia S A | MINOCYCINE PREPARATION PROCESS CRYSTALLINE |
GB0703909D0 (en) | 2007-02-28 | 2007-04-11 | Neuropharm Ltd | Treatment of anxiety disorders |
FR2915891B1 (en) | 2007-05-10 | 2012-05-11 | Oreal | FOAM COMPOSITION COMPRISING A SILICONE POLYMER |
US9511016B2 (en) | 2007-06-12 | 2016-12-06 | Epicentrx, Inc. | Topical composition for treating pain |
US8636982B2 (en) | 2007-08-07 | 2014-01-28 | Foamix Ltd. | Wax foamable vehicle and pharmaceutical compositions thereof |
WO2009056991A2 (en) | 2007-09-04 | 2009-05-07 | Foamix Ltd. | Device for delivery of a foamable composition |
GEP20125661B (en) | 2007-09-30 | 2012-10-10 | Meda Ab | Silicone gel-based compositions for wound healing and scar removal |
US20090130029A1 (en) | 2007-11-21 | 2009-05-21 | Foamix Ltd. | Glycerol ethers vehicle and pharmaceutical compositions thereof |
WO2009069006A2 (en) | 2007-11-30 | 2009-06-04 | Foamix Ltd. | Foam containing benzoyl peroxide |
WO2009090495A2 (en) | 2007-12-07 | 2009-07-23 | Foamix Ltd. | Oil and liquid silicone foamable carriers and formulations |
US8518376B2 (en) | 2007-12-07 | 2013-08-27 | Foamix Ltd. | Oil-based foamable carriers and formulations |
CA2711703A1 (en) | 2008-01-08 | 2009-07-16 | Foamix Ltd. | Sensation modifying topical composition foam |
EP2242476A2 (en) | 2008-01-14 | 2010-10-27 | Foamix Ltd. | Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses |
US8652443B2 (en) | 2008-02-14 | 2014-02-18 | Precision Dermatology, Inc. | Foamable microemulsion compositions for topical administration |
ES2330291B1 (en) | 2008-02-29 | 2010-10-18 | Lipotec Sa | USEFUL PEPTIDES IN THE TREATMENT OF SKIN, MUCOSAS AND / OR LEATHER HAIR AND ITS USE IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS. |
MX2010009693A (en) | 2008-03-05 | 2010-12-20 | Paratek Pharm Innc | Minocycline compounds and methods of use thereof. |
RU2015109165A (en) | 2008-03-06 | 2015-11-10 | Анакор Фармасьютикалз, Инк. | WOODEN SMALL MOLECULES AS ANTI-INFLAMMATORY AGENTS |
US20120141384A1 (en) | 2008-05-06 | 2012-06-07 | Dov Tamarkin | Antibacterial conjugated boronic acids and pharmaceutical compositions thereof |
KR101534422B1 (en) * | 2008-05-14 | 2015-07-09 | 오토노미, 인코포레이티드 | Controlled release corticosteroid compositions and methods for the treatment of otic disorders |
BRPI0914630A2 (en) | 2008-06-26 | 2019-09-24 | Anterios Inc | dermal release |
US8253882B2 (en) | 2008-08-07 | 2012-08-28 | Sharp Kabushiki Kaisha | Display device |
EP2332297B1 (en) | 2008-08-08 | 2018-10-03 | InterDigital Patent Holdings, Inc. | Method and apparatus for reporting a buffer status |
CN102196821A (en) | 2008-10-31 | 2011-09-21 | 莫贝里德尔马公司 | Topical composition comprising a combination of at least two penetration enhancing agents |
WO2010068465A2 (en) | 2008-11-25 | 2010-06-17 | Citrix Systems. Inc. | Systems and methods for maintaining persistence by a backup virtual server |
EP2210588B1 (en) | 2008-12-23 | 2011-03-09 | Intendis GmbH | Foamable composition essentially free of pharmaceutically active ingredients for the treatment of human skin |
JP5213734B2 (en) | 2009-01-22 | 2013-06-19 | サンウエーブ工業株式会社 | Cabinet with flap door |
WO2010093382A1 (en) | 2009-02-12 | 2010-08-19 | Collegium Pharmaceutical, Inc. | Foamable benzoyl peroxide compositions for topical administration |
PT2400951T (en) | 2009-02-25 | 2018-11-26 | Mayne Pharma Llc | Topical foam composition |
WO2010124280A2 (en) | 2009-04-24 | 2010-10-28 | New Century Pharmaceuticals, Inc. | Human serum albumin-based topical ointment for treatment of acne, psoriasis, egfr-induced toxicity, premature skin aging and other skin conditions |
CA2760186C (en) | 2009-04-28 | 2019-10-29 | Foamix Ltd. | Foamable vehicle and pharmaceutical compositions comprising aprotic polar solvents and uses thereof |
PT104644B (en) | 2009-06-26 | 2012-11-06 | Hovione Farmaciencia S A | Topical formulation containing a tetracycline and a method of treating skin infections using the same |
US8255186B2 (en) | 2009-07-09 | 2012-08-28 | Air Liquide Large Industries U.S. Lp | Presenting dynamic SCADA data |
WO2011013008A2 (en) | 2009-07-29 | 2011-02-03 | Foamix Ltd. | Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses |
CA2769625C (en) | 2009-07-29 | 2017-04-11 | Foamix Ltd. | Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses |
US20110052506A1 (en) | 2009-08-31 | 2011-03-03 | Collegium Pharmaceutical, Inc. | Stable Aerosol Topical Foams Comprising a Hypochlorite Salt |
US20140186269A1 (en) | 2013-01-03 | 2014-07-03 | Foamix Ltd. | Vehicle compositions essentially free of pharmaceutically active agents for the improved treatment of acne and related disorders |
GB2474930B (en) | 2009-10-02 | 2012-07-04 | Foamix Ltd | Topical tetracycline compositions |
MX359879B (en) | 2009-10-02 | 2018-10-12 | Foamix Pharmaceuticals Ltd | Topical tetracycline compositions. |
US9849142B2 (en) | 2009-10-02 | 2017-12-26 | Foamix Pharmaceuticals Ltd. | Methods for accelerated return of skin integrity and for the treatment of impetigo |
US20140121188A1 (en) | 2009-10-02 | 2014-05-01 | Foamix Ltd. | Compositions for the improved treatment of acne and related disorders |
US8735377B1 (en) | 2010-02-04 | 2014-05-27 | Susan Anna Sipos | Methods of treating herpes zoster |
US20110212035A1 (en) | 2010-02-26 | 2011-09-01 | Collegium Pharmaceutical, Inc. | Emollient foams for treatment of dermatoses |
WO2011115700A2 (en) | 2010-03-18 | 2011-09-22 | Precision Dermatology, Inc. | Emollient foams for treatment of seborrheic dermatitis |
WO2011119585A2 (en) | 2010-03-26 | 2011-09-29 | Precision Dermatology, Inc. | Aerosol foams comprising clindamycin phosphate |
US20120076766A1 (en) | 2010-04-21 | 2012-03-29 | Phillips D Howard | Topical drug delivery system with dual carriers |
US20130053353A1 (en) | 2010-05-04 | 2013-02-28 | Foamix Ltd. | Compositions, gels and foams with rheology modulators and uses |
ES2918299T3 (en) | 2010-06-11 | 2022-07-15 | Prec Dermatology Inc | High oil content emollient spray foam compositions |
WO2012007843A2 (en) | 2010-07-12 | 2012-01-19 | Foamix Ltd. | Apparatus and method for releasing a unit dose of content from a container |
WO2012021629A2 (en) | 2010-08-11 | 2012-02-16 | Philadelphia Health & Education Corporation | Novel d3 dopamine receptor agonists to treat dyskinesia in parkinson's disease |
US20120064136A1 (en) | 2010-09-10 | 2012-03-15 | Nanobio Corporation | Anti-aging and wrinkle treatment methods using nanoemulsion compositions |
US20120093876A1 (en) | 2010-10-13 | 2012-04-19 | Aciex, Inc. | Ophthalmic Formulations, Methods Of Manufacture And Methods of Normalizing Meibomian Gland Secretions |
US8895536B2 (en) | 2010-10-29 | 2014-11-25 | Infirst Healthcare Ltd. | Compositions and methods for treating chronic inflammation and inflammatory diseases |
FR2969492B1 (en) | 2010-12-23 | 2013-07-05 | Galderma Res & Dev | DERMATOLOGICAL FOAMS OBTAINED FROM GEL OR SUSPENSION CONTAINING ADAPALENE |
CN103781485A (en) | 2011-01-19 | 2014-05-07 | 护肤品实验室有限公司 | Topical minocycline compositions and methods of using the same |
US20140221320A1 (en) | 2011-07-08 | 2014-08-07 | The Research Foundation For The State University Of New York | Topical minocycline ointment for suppression of allergic skin responses |
CA2854449A1 (en) | 2011-11-03 | 2013-05-10 | Precision Dermatology, Inc. | Stable dermatological aerosol foams utilizing reactive propellants |
US8801680B2 (en) | 2012-03-14 | 2014-08-12 | Becton, Dickinson And Company | Angled retracting sheath for safety needle |
IL225246A0 (en) | 2012-03-15 | 2013-06-27 | Meir Eini | Methods for accelerated return of skin integrity and for the treatment of impetigo |
BR112014023379A8 (en) | 2012-03-22 | 2017-07-25 | Prec Dermatology Inc | MICROEMULSIONS BASED ON CYCLODEXTRIN AND DERMATOLOGICAL USES THEREOF |
CA2775393C (en) | 2012-05-02 | 2014-04-29 | Samy Saad | Topical non-aqueous pharmaceutical formulations |
EP2850870B1 (en) | 2012-05-15 | 2017-02-01 | Telefonaktiebolaget LM Ericsson (publ) | Interference management for network assisted device-to-device communication |
EP2872146A4 (en) | 2012-07-13 | 2016-01-06 | Paratek Pharm Innc | Tetracycline compounds for treating neurodegenerative disorders |
PT106679B (en) | 2012-11-27 | 2015-03-25 | Hovione Farmaciencia Sa | TOPICAL FORMULATIONS OF TETRACYCLINES, THEIR PREPARATION AND USES |
US8778365B1 (en) | 2013-01-31 | 2014-07-15 | Merz Pharmaceuticals, Llc | Topical compositions and methods for making and using same |
CN105338950A (en) | 2013-02-22 | 2016-02-17 | 施泰福实验室股份有限公司 | Non-aqueous solid stabilized emulsions |
JP2016510034A (en) | 2013-02-28 | 2016-04-04 | プレシジョン ダーマトロジー インコーポレイテッドPrecision Dermatology, Inc. | Topical corticosteroid preparation with improved bioavailability |
WO2014134427A1 (en) | 2013-02-28 | 2014-09-04 | Precision Dermatology, Inc. | Controlling the bioavailability of active ingredients in topical formulations |
EP2968372A1 (en) | 2013-03-15 | 2016-01-20 | ReVance Therapeutics, Inc. | Minocycline derivatives |
BR112015030501A2 (en) | 2013-06-04 | 2017-07-25 | Vyome Biosciences Pvt Ltd | coated particles and compositions comprising them |
US20160120803A1 (en) | 2013-06-17 | 2016-05-05 | Contract Pharmaceuticals Limited | Non-aerosol foams for topical administration |
WO2015066717A1 (en) | 2013-11-04 | 2015-05-07 | BioPharmX, Inc. | Dosage form comprising an active ingredient and a plurality of solid porous microcarriers |
WO2015075640A1 (en) | 2013-11-20 | 2015-05-28 | Lupin Limited | Stable pharmaceutical formulation(s) of tetracycline antibiotic |
PT107433B (en) | 2014-01-28 | 2018-12-04 | Hovione Farm S A | PARTICLE SIZE REDUCTION AND CONTROL PROCESS |
WO2015153864A2 (en) | 2014-04-02 | 2015-10-08 | Hopkins Patricia T | Methods for treating inflammatory conditions |
US9841142B2 (en) | 2014-12-22 | 2017-12-12 | Rockwell Automation Technologies, Inc. | Single-wire industrial safety system with safety device diagnostic communication |
TW201705962A (en) | 2015-03-23 | 2017-02-16 | 生物製藥X公司 | Pharmaceutical tetracycline composition for dermatological use |
US20160287615A1 (en) | 2015-04-03 | 2016-10-06 | BioPharmX, Inc. | Novel encapsulation of fluorescent, photo-sensitive, or oxygen-sensitive active ingredient for topical application |
WO2016205172A1 (en) | 2015-06-15 | 2016-12-22 | Banner Life Sciences Llc | Soft lozenges comprising corticosteroids |
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EP3346998A4 (en) | 2015-08-17 | 2019-08-28 | Sidmak Laboratories (India) PVT. Ltd. | Topical film delivery system |
WO2017029647A1 (en) | 2015-08-20 | 2017-02-23 | Meir Eini | Tetracycline management of egfr inhibitor associated dermatoses |
PT108978B (en) | 2015-11-24 | 2020-03-09 | Hovione Farm S A | TETRACYCLINE SALTS |
CA2978573A1 (en) | 2016-09-08 | 2018-03-08 | Foamix Pharmaceuticals Ltd. | Compositions and methods for treating rosacea and acne |
JP2021500369A (en) | 2017-10-24 | 2021-01-07 | グレンマーク・ファーマシューティカルズ・リミテッド | Topical pharmaceutical compositions of adapalene and minocycline |
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