US20110123577A1 - Method Of Delivering Stable Topical Drug Compositions - Google Patents
Method Of Delivering Stable Topical Drug Compositions Download PDFInfo
- Publication number
- US20110123577A1 US20110123577A1 US13/019,101 US201113019101A US2011123577A1 US 20110123577 A1 US20110123577 A1 US 20110123577A1 US 201113019101 A US201113019101 A US 201113019101A US 2011123577 A1 US2011123577 A1 US 2011123577A1
- Authority
- US
- United States
- Prior art keywords
- polyglycol
- drug
- carrier
- phosphatidylcholine
- molecular weight
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/095—Oxytocins; Vasopressins; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/23—Calcitonins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH] (Somatotropin)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/31—Somatostatins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/56—Protease inhibitors from plants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
Definitions
- the present invention relates to topical drug delivery compositions and methods of transdermal drug delivery. More specifically, the present invention relates to stable drug delivery compositions for topical administration.
- Topical drug delivery systems are known. These systems deliver drugs, therapeutic agents and other desired substances transdermally and may be designed to act locally at the point of application or to act systemically once entering the body's blood circulation. In these systems, delivery may be achieved by means such as direct topical application of a substance or drug in the form of an ointment or the like, or by adhesion of a patch with a reservoir or the like that holds the drug and releases it to the skin in a time-controlled fashion.
- Transdermal delivery systems for agents such as drugs, pain relieving compounds, vitamins, and skin improving compounds have been in use for a number of years. These transdermal delivery systems using creams have been developed for use with analgesics and skin refining compounds. Transdermal systems using a patch have been developed for nicotine and estrogen therapies, for instance, estradiol technology described in U.S. Pat. No. 6,521,250 to Meconi, et al.
- a composition for transdermal delivery of a macromolecule comprises a phosphatidylcholine carrier component entrapping the macromolecule, wherein the carrier component stabilizes the macromolecule at room temperature.
- a method for administering a drug or other active agent comprises applying to skin composition containing an effective amount of the drug or active agent, a carrier having a phosphatidylcholine component entrapping the drug or active agent.
- Phosphatidylcholine is used as a carrier for the topical delivery of polypeptides and macromolecules in the practice of this invention.
- Phosphatidylcholine is a basic component of cell membrane bilayers and the main phospholipid circulating in the plasma.
- Phosphatidylcholine is highly absorbable and supplies choline which is needed to facilitate movement of fats and oils across and maintain cell membranes in animals.
- Topical delivery compositions of the present invention are non-polar and formulated to contain polypeptides and macromolecules soluble in phosphatidylcholine, which are then applied to skin for transdermal delivery of the macromolecule.
- Topical delivery compositions of the invention are efficacious in the delivery of macromolecular drugs that are conventionally administered intramuscularly, intravenously or orally, including, but not limited to polypeptides such as insulin and somatropin, prostaglandins, glucocorticoids, estrogens, androgens, and the like.
- topical administration of a composition and transdermal delivery of the drug or active agent therein is easier and pleasanter as an administration route than injections, particularly for drugs such as insulin that must be given to patients over a period of time, or for a lifetime. Furthermore, unlike oral administration where a substantial amount of the drug can be destroyed in the digestive process, the drugs in a topical application are not wasted. Topical application allows a steady diffusion of the drug to the desired target area without the cyclic dosages typical of orally or parenterally administered drugs.
- phosphatidylcholine as used herein means a mixture of stearic, palmitic, and oleic acid diglycerides linked to the choline ester of phosphoric acid, commonly called lecithin.
- lecithin many commercial lecithin products are available, such as, for example, those sold under the tradenames Lecithol®, Vitellin®, Kelecin®, and Granulestin® because lecithin is widely used in the food industry.
- Compositions of the invention can contain synthetic or natural lecithin, or mixtures thereof. Natural preparations are preferred because they exhibit desirable physical characteristics and are both economical and nontoxic.
- Preferred topical delivery compositions of the present invention additionally contain polyenylphosphatidylcholine (herein abbreviated “PPC”) to enhance epidermal penetration.
- PPC polyenylphosphatidylcholine
- the term “polyenylphosphatidylcholine” as used herein means any phosphatidylcholine bearing two fatty acid substituents, wherein at least one is an unsaturated fatty acid with at least two double bonds such as linoleic acid.
- soybean lecithin and soybean fractions for example, contain higher levels of polyenylphosphatidylcholine, with dilinoleoyl-phosphatidylcholine (18:2-18:2 phosphatidylcholine) as the most abundant phosphatidylcholine species, than conventional food grade lecithin, and are useful in formulating topical delivery compositions of the invention.
- conventional soybean lecithin is enriched with polyenylphosphatidylcholine by adding soybean extracts containing high levels of polyenylphosphatidylcholine.
- this type of phosphatidylcholine is called “polyenylphosphatidyl-choline-enriched” phosphatidylcholine (hereinafter referred to as PPC-enriched phosphatidylcholine), even where the term encompasses lecithin obtained from natural sources exhibiting polyenylphosphatidylcholine levels higher than ordinary soybean varieties.
- PPC-enriched phosphatidylcholine polyenylphosphatidyl-choline-enriched phosphatidylcholine
- Rhône-Poulenc's product is a soybean extract containing about 42% dilinoleoylphosphatidylcholine and about 24% palmitoyllinoleylphosphatidylcholine (16:0-18:2 PC) as the major phosphatidylcholine components.
- the PPC-enriched phosphatidylcholine forms a bilayer enveloping the polypeptide or macromolecule to create the topical drug delivery composition, contributing to the stability of the active molecule and enhancing penetration.
- the topical drug delivery composition may be in liquid crystal phase, with the PPC-enriched phosphatidylcholine loosely arranged in multilamellar fashion, with the polypeptide or macromolecule being bonded and entrapped within the lipid bilayers formed therein, as disclosed in U.S. patent application Ser. No. 10/448,632 to Perricone. This forms a loosely arranged, yet stable, PPC-enriched phosphatidylcholine-drug complex that further increases penetration and delivery of the polypeptide or macromolecule to the dermal vasculature.
- Topical drug delivery compositions of the present invention provide an administration route that is a marked improvement over conventional insulin injections, considerably easier and pleasanter. It is a further advantage that compositions of the invention are also stable at room temperature, providing considerable convenience for insulin users who, in the past, have had to deal with the refrigerated insulin products commercially available. Also, insulin compositions according to the present invention have longer shelf lives (whether stored at room temperature or refrigerated) and will not denature at room temperature as would traditional insulin treatments.
- Insulin useful in the topical drug delivery compositions of the present invention is commercially available from a variety of sources, marketed under the tradenames Humulin®, Novolin®, Humalog®, Inutral®, among others. Some of these products contain porcine sequences.
- Compositions of the invention are preferably formulated with recombinant human polypeptides such as those obtained from Sigma Co., Spectrum Chemicals and Laboratories, and similar vendors and employed in the examples that follow. It is an advantage of the invention that topical drug delivery compositions carrying insulin are formulated with commercially available ingredients.
- Topical drug delivery compositions are generally formulated with a carrier comprising a PPC-enriched phosphatidylcholine material with the trade name NAT 8729 (commercially available from vendors such as Rhône-Poulenc and American Lecithin Company) and at least one polyglycol (polyhydric alcohol of a monomeric glycol such as polyethylene glycol (PEG) having molecular weights of 200, 300, 400, 600,1000,1450, 3350, 4000, 6000, 8000 and 20000.
- a carrier comprising a PPC-enriched phosphatidylcholine material with the trade name NAT 8729 (commercially available from vendors such as Rhône-Poulenc and American Lecithin Company) and at least one polyglycol (polyhydric alcohol of a monomeric glycol such as polyethylene glycol (PEG) having molecular weights of 200, 300, 400, 600,1000,1450, 3350, 4000, 6000, 8000 and 20000.
- PEG poly
- this carrier may comprise a surfactant such as a siloxylated polyether comprising dimethyl, methyl(propylpolyethylene oxide propylene oxide, acetate) siloxane or silicone glycol copolymer fluid commercially available from vendors such as Dow Corning, e.g. poly(oxyehtylene.oxypropylene) methyl polysiloxanne copolymer sold under the tradename Dow Corning 190 surfactant, and lubricant such as silicone fluids containing low viscosity polydimethylsiloxane polymers, methylparaben (p-hydroxy benzoic acid methyl ester) commercially available from vendors such as Down Corning (under the tradename Dow Corning 200 silicone fluid).
- a surfactant such as a siloxylated polyether comprising dimethyl, methyl(propylpolyethylene oxide propylene oxide, acetate) siloxane or silicone glycol copolymer fluid commercially available from vendors such as Dow Corning, e.g. poly(
- purified water may be added to the carrier.
- the carrier is then mixed with a preparation of the particular polypeptide(s) or macromolecule(s) in an amount to obtain the desired strength in the final composition.
- Stable insulin topical preparations were formulated by first preparing a base solution.
- NAT 8729 (45% w/w) was shaved and added to a mixture of polyglycol E200 (50% w/w) and polyglycol E400 (5% w/w) both obtained from Dow Corning.
- the base solution was then covered well and lightning mixed with a special disintegration head impeller slowly at 800 rpm with slight heat. The temperature did not go above 40° C. Typical mixing times were 5 hours.
- the final solution is a crystal clear, viscous amber solution with no sediments or separations.
- the methylparaben was first added to the base solution and mixed for at least an hour until a complete solution formed. Then the Dow Corning 200-5 or 10 cst was slowly added and mixed until a clear solution formed. Afterwards the Dow Corning Fluid 190 was added slowly and mixed into the solution to form the carrier.
- Insulin preparations of the invention were then made using the carrier in two strengths: 50 units and 100 units, by simply dissolving RNA-derived recombinant human insulin obtained from Sigma into the carrier. It was readily soluble in the carrier.
- insulin standards were prepared at 1 mg/ml in 0.01 N HCl using Sigma insulin. (One mg of this material exhibits an activity of 28 insulin units.) Stable insulin compositions samples were prepared at 1 mg/1 ml base by mixing at room temperature for 60 minutes. This mixture was then divided in half, half of which was stored at 4° C., and the other half stored at room temperature. Separation analyses, High Performance Liquid Chromatography (RP-HPLC) and High Performance Capillary Electrophoresis (HPCE), of insulin standards and insulin compositions of the invention which were stored at different temperatures for different periods of time were performed.
- RP-HPLC High Performance Liquid Chromatography
- HPCE High Performance Capillary Electrophoresis
- Stable insulin compositions were formulated by first preparing a base solution.
- Polyglycol E200 (PEG-200) (50% w/w) was weighed and polyglycol E400 (PEG-400) (5% w/w) was added to the same container to obtain the desired weight, (both obtained from Dow Corning).
- PEG-200 and PEG-400 were lightning mixed at 38-40° C. with IKA model RW20 using a disintegration head impeller slowly at 800 rpm (speed 1), yielding PEG-200/PEG-400 solution.
- NAT 8729 containing 80.6% PPC-enriched phosphatidylcholine and 4.9% lysophosphatidylcholine was obtained from Rhône-Poulenc.
- NAT 8729 (45% w/w) was shaved and added to PEG-200/PEG-400 solution, covered and mixed, with temperature not exceeding 40° C., until a clear, viscous amber solution with no sediments or separations resulted. The mixing time was approximately five hours.
- An alternative mixture can be prepared by covering and mixing the solution overnight without heat for a 95-96% yield. The solution was removed from heat and transferred to Ross Homogenizer (Model HSM100LC) using smallest mesh screen.
- Dow Corning Fluid denominated 190 1.00% w/w
- Dow Corning Fluid denoted 200-5 or 10 cst 1.00% w/w
- silicone fluids containing low viscosity polydimethylsiloxane polymers were mixed together in a container with a clean spatula.
- the solution (53.25% w/w) was warmed to 40° C. and mixed at 800 rpm. Typical mixing times were approximately 5 hours. The solution was then milled at 3800 rpm and the Dow Corning Fluid mixture was added very slowly until a clear solution resulted. Methyl Paraben (p-hydroxy benzoic acid methyl ester) obtained from Mallinckrodt (0.75% w/w) was added at once and mixed until a complete solution resulted. Purified water warmed to 40° C. was added very slowly to solution while milling at 7500 rpm for about three minutes. At end of milling, speed was increased to 10,000 rpm for few seconds before stopping. The solution was removed and swept with paddle head using IKA Model RW-20 until cooled to room temperature.
- This step is very critical and if it is not done properly it will generate a biphasic end product.
- the general rule is to use a container having a volume twice that of the solution so the homogenizer head is well embedded in the solution. The solution was then cooled to room temperature.
- USP human recombinant insulin in obtained from Spectrum Chemicals and Laboratories was prepared in 0.01 N HCl at 50 mg/ml, and gently, yet well mixed. This insulin preparation was then added very slowly to the above solution to obtain a final concentration of 500 units/ml or 20 mg/ml. Mixing was continued at room temperature for at least one hour. The final stable insulin composition was stored at 4° C. in amber air-tight container.
- Stable topical drug delivery compositions of the present invention may be employed to deliver and stabilize polypeptides transdermally, including but not limited to insulin, oxytocin, vasopressin, insulin, somatotropin, calcitonin, chorionic gonadotropin, menotropins, follitropins, somatostatins, progestins, and combinations of any of these.
- polypeptides transdermally, including but not limited to insulin, oxytocin, vasopressin, insulin, somatotropin, calcitonin, chorionic gonadotropin, menotropins, follitropins, somatostatins, progestins, and combinations of any of these.
- Somatotropin pituitary growth hormone
- a drug delivery composition formulated with somatotropin was formulated in one trial with 85% phosphatidylcholine to which lipoic acid and ascorbyl palmitate were added. Somatotropin readily dispersed in phosphatidyl-choline and remained stable in it. Growth hormone appeared to penetrate the skin well when the composition was topically applied.
- the present invention may also be used to provide topical delivery of active agents other that drugs, for example, skin care agents.
- the invention is particularly useful with large molecules that are used in some cosmetic formulations, including peptides and polymers.
Abstract
A method of delivering a drug composition comprises providing a carrier having a phosphatidylcholine component and a drug entrapped therein, and applying the composition to the skin for transdermal delivery of the drug, wherein the composition is stable at room temperature.
Description
- This application is a continuation of U.S. patent application Ser. No. 11/344,442 filed Jan. 31, 2006, now pending, which is divisional application of U.S. patent application Ser. No. 10/749,914 filed Dec. 31, 2003, now U.S. Pat. No. 7,182,956 issued Feb. 27, 2007, which claimed priority benefits under 35 U.S.C. §119(e) of U.S. Provisional Patent Application Ser. No. 60/437,279 filed Dec. 31, 2002. This application is also a continuation of copending U.S. patent application Ser. No. 11/334,206 for “Topical Drug Delivery Using Phasphatidylcholine”, filed Jan. 18, 2006, which is a divisional patent application of copending U.S. patent application Ser. No. 10/448,632 for “Topical Drug Delivery Using Phosphatidylcholine,” filed May 30, 2003, which claims priority benefits under 35 U.S.C. §119(e) of U.S. Provisional Patent Application Ser. No. 60/384,597 filed May 31, 2002.
- The present invention relates to topical drug delivery compositions and methods of transdermal drug delivery. More specifically, the present invention relates to stable drug delivery compositions for topical administration.
- Topical drug delivery systems are known. These systems deliver drugs, therapeutic agents and other desired substances transdermally and may be designed to act locally at the point of application or to act systemically once entering the body's blood circulation. In these systems, delivery may be achieved by means such as direct topical application of a substance or drug in the form of an ointment or the like, or by adhesion of a patch with a reservoir or the like that holds the drug and releases it to the skin in a time-controlled fashion.
- Transdermal delivery systems for agents such as drugs, pain relieving compounds, vitamins, and skin improving compounds have been in use for a number of years. These transdermal delivery systems using creams have been developed for use with analgesics and skin refining compounds. Transdermal systems using a patch have been developed for nicotine and estrogen therapies, for instance, estradiol technology described in U.S. Pat. No. 6,521,250 to Meconi, et al.
- While effective for their purpose, these systems have typically only been useful for transdermal delivery of relatively small molecules. The skin's porous structure permits such small molecules to pass from the epidermis to the dermis via diffusion. However, large molecules, such as insulin, are not able to diffuse through the skin and cannot be delivered by these known means. One such solution has been provided in U.S. patent application Ser. No. 10/448,632 to Perricone, the disclosure of which is incorporated herein by reference.
- While the delivery of large molecules such as insulin have been addressed, such systems do not address the storage and retention of the effectiveness of the drug to be delivered. Many pharmaceuticals and biologically active compounds, such as insulin, must be kept cool and away from heat to remain effective and prevent denaturing at ambient temperatures. Such substances may not be stored or carried (without refrigeration) by the user. Often drugs like insulin must be administered throughout the day and should be in ready-access to or carried by the user, which may expose the compound to high temperatures. As such, there remains a need to stabilize compositions, including insulin, so that they are resistant to warmer temperatures and have a longer life at these temperatures without a need for refrigeration
- A composition for transdermal delivery of a macromolecule comprises a phosphatidylcholine carrier component entrapping the macromolecule, wherein the carrier component stabilizes the macromolecule at room temperature.
- A method for administering a drug or other active agent comprises applying to skin composition containing an effective amount of the drug or active agent, a carrier having a phosphatidylcholine component entrapping the drug or active agent.
- Phosphatidylcholine is used as a carrier for the topical delivery of polypeptides and macromolecules in the practice of this invention. Phosphatidylcholine is a basic component of cell membrane bilayers and the main phospholipid circulating in the plasma. Phosphatidylcholine is highly absorbable and supplies choline which is needed to facilitate movement of fats and oils across and maintain cell membranes in animals.
- Topical delivery compositions of the present invention are non-polar and formulated to contain polypeptides and macromolecules soluble in phosphatidylcholine, which are then applied to skin for transdermal delivery of the macromolecule. Topical delivery compositions of the invention are efficacious in the delivery of macromolecular drugs that are conventionally administered intramuscularly, intravenously or orally, including, but not limited to polypeptides such as insulin and somatropin, prostaglandins, glucocorticoids, estrogens, androgens, and the like.
- It is an advantage of the invention that topical administration of a composition and transdermal delivery of the drug or active agent therein is easier and pleasanter as an administration route than injections, particularly for drugs such as insulin that must be given to patients over a period of time, or for a lifetime. Furthermore, unlike oral administration where a substantial amount of the drug can be destroyed in the digestive process, the drugs in a topical application are not wasted. Topical application allows a steady diffusion of the drug to the desired target area without the cyclic dosages typical of orally or parenterally administered drugs.
- The term “phosphatidylcholine” as used herein means a mixture of stearic, palmitic, and oleic acid diglycerides linked to the choline ester of phosphoric acid, commonly called lecithin. Many commercial lecithin products are available, such as, for example, those sold under the tradenames Lecithol®, Vitellin®, Kelecin®, and Granulestin® because lecithin is widely used in the food industry. Compositions of the invention can contain synthetic or natural lecithin, or mixtures thereof. Natural preparations are preferred because they exhibit desirable physical characteristics and are both economical and nontoxic.
- Preferred topical delivery compositions of the present invention additionally contain polyenylphosphatidylcholine (herein abbreviated “PPC”) to enhance epidermal penetration. The term “polyenylphosphatidylcholine” as used herein means any phosphatidylcholine bearing two fatty acid substituents, wherein at least one is an unsaturated fatty acid with at least two double bonds such as linoleic acid. Certain types of soybean lecithin and soybean fractions, for example, contain higher levels of polyenylphosphatidylcholine, with dilinoleoyl-phosphatidylcholine (18:2-18:2 phosphatidylcholine) as the most abundant phosphatidylcholine species, than conventional food grade lecithin, and are useful in formulating topical delivery compositions of the invention. Alternatively, conventional soybean lecithin is enriched with polyenylphosphatidylcholine by adding soybean extracts containing high levels of polyenylphosphatidylcholine. As used herein, this type of phosphatidylcholine is called “polyenylphosphatidyl-choline-enriched” phosphatidylcholine (hereinafter referred to as PPC-enriched phosphatidylcholine), even where the term encompasses lecithin obtained from natural sources exhibiting polyenylphosphatidylcholine levels higher than ordinary soybean varieties. These products are commercially available from American Lecithin Company, Rhône-Poulenc and other lecithin vendors. American Lecithin Company markets its products with a “U” designation, indicating high levels of unsaturation; Rhône-Poulenc's product is a soybean extract containing about 42% dilinoleoylphosphatidylcholine and about 24% palmitoyllinoleylphosphatidylcholine (16:0-18:2 PC) as the major phosphatidylcholine components.
- While not wishing to be bound to any theory, it is believed that the PPC-enriched phosphatidylcholine forms a bilayer enveloping the polypeptide or macromolecule to create the topical drug delivery composition, contributing to the stability of the active molecule and enhancing penetration. Further, the topical drug delivery composition may be in liquid crystal phase, with the PPC-enriched phosphatidylcholine loosely arranged in multilamellar fashion, with the polypeptide or macromolecule being bonded and entrapped within the lipid bilayers formed therein, as disclosed in U.S. patent application Ser. No. 10/448,632 to Perricone. This forms a loosely arranged, yet stable, PPC-enriched phosphatidylcholine-drug complex that further increases penetration and delivery of the polypeptide or macromolecule to the dermal vasculature.
- The disclosure of U.S. patent application Ser. No. 11/334,206 for “Topical Drug Delivery Using Phasphatidylcholine”, filed Jan. 18, 2006 is hereby incorporated by reference.
- Topical drug delivery compositions of the present invention provide an administration route that is a marked improvement over conventional insulin injections, considerably easier and pleasanter. It is a further advantage that compositions of the invention are also stable at room temperature, providing considerable convenience for insulin users who, in the past, have had to deal with the refrigerated insulin products commercially available. Also, insulin compositions according to the present invention have longer shelf lives (whether stored at room temperature or refrigerated) and will not denature at room temperature as would traditional insulin treatments.
- Insulin useful in the topical drug delivery compositions of the present invention is commercially available from a variety of sources, marketed under the tradenames Humulin®, Novolin®, Humalog®, Inutral®, among others. Some of these products contain porcine sequences. Compositions of the invention are preferably formulated with recombinant human polypeptides such as those obtained from Sigma Co., Spectrum Chemicals and Laboratories, and similar vendors and employed in the examples that follow. It is an advantage of the invention that topical drug delivery compositions carrying insulin are formulated with commercially available ingredients.
- Topical drug delivery compositions are generally formulated with a carrier comprising a PPC-enriched phosphatidylcholine material with the trade name NAT 8729 (commercially available from vendors such as Rhône-Poulenc and American Lecithin Company) and at least one polyglycol (polyhydric alcohol of a monomeric glycol such as polyethylene glycol (PEG) having molecular weights of 200, 300, 400, 600,1000,1450, 3350, 4000, 6000, 8000 and 20000. Further, this carrier may comprise a surfactant such as a siloxylated polyether comprising dimethyl, methyl(propylpolyethylene oxide propylene oxide, acetate) siloxane or silicone glycol copolymer fluid commercially available from vendors such as Dow Corning, e.g. poly(oxyehtylene.oxypropylene) methyl polysiloxanne copolymer sold under the tradename Dow Corning 190 surfactant, and lubricant such as silicone fluids containing low viscosity polydimethylsiloxane polymers, methylparaben (p-hydroxy benzoic acid methyl ester) commercially available from vendors such as Down Corning (under the tradename Dow Corning 200 silicone fluid). Additionally, purified water may be added to the carrier. The carrier is then mixed with a preparation of the particular polypeptide(s) or macromolecule(s) in an amount to obtain the desired strength in the final composition. The following examples are presented to further illustrate and explain the present invention and should not be taken as limiting in any regard.
- Stable insulin topical preparations were formulated by first preparing a base solution. A polyenylphosphatidylcholine material denoted NAT 8729 which contained 80.6% PPC-enriched phosphatidylcholine and 4.9% lysophosphatidylcholine was obtained from Rhône-Poulenc. NAT 8729 (45% w/w) was shaved and added to a mixture of polyglycol E200 (50% w/w) and polyglycol E400 (5% w/w) both obtained from Dow Corning. The base solution was then covered well and lightning mixed with a special disintegration head impeller slowly at 800 rpm with slight heat. The temperature did not go above 40° C. Typical mixing times were 5 hours. The final solution is a crystal clear, viscous amber solution with no sediments or separations.
- Into this base solution (97.25% w/w) was then mixed a Dow Corning Fluid 190 (1.00% w/w) [a siloxylated polyether comprising dimethyl, methyl(propylpolyethylene oxide propylene oxide, acetate) siloxane]; a Dow Corning silicone fluid denoted 200-5 or 10 cst (1.00% w/w) [silicone fluids containing low viscosity polydimethylsiloxane polymers]; and methylparaben [p-hydroxy benzoic acid methyl ester] obtained from vendor Mallinckrodt (0.75% w/w). The ingredients were homogenized with 3850 rpm with a 0.45 micron screen as follows. The methylparaben was first added to the base solution and mixed for at least an hour until a complete solution formed. Then the Dow Corning 200-5 or 10 cst was slowly added and mixed until a clear solution formed. Afterwards the Dow Corning Fluid 190 was added slowly and mixed into the solution to form the carrier.
- Insulin preparations of the invention were then made using the carrier in two strengths: 50 units and 100 units, by simply dissolving RNA-derived recombinant human insulin obtained from Sigma into the carrier. It was readily soluble in the carrier.
- In testing the stability of the stable insulin composition, insulin standards were prepared at 1 mg/ml in 0.01 N HCl using Sigma insulin. (One mg of this material exhibits an activity of 28 insulin units.) Stable insulin compositions samples were prepared at 1 mg/1 ml base by mixing at room temperature for 60 minutes. This mixture was then divided in half, half of which was stored at 4° C., and the other half stored at room temperature. Separation analyses, High Performance Liquid Chromatography (RP-HPLC) and High Performance Capillary Electrophoresis (HPCE), of insulin standards and insulin compositions of the invention which were stored at different temperatures for different periods of time were performed.
- The RP-HPLC and HPCE analyses indicated that insulin standards that were stored at 4° C. or −20° C. were stable after 65 days, but insulin standards stored at room temperature started to denature within 7 days. The RP-HPLC and HPCE profiles of insulin compositions of the invention, on the other hand, were stable at both room temperature and at 4° C., and did not change after 65 days. The results clearly showed that the carrier prevented the denaturing of the insulin stored at room temperature.
- Stable insulin compositions were formulated by first preparing a base solution. Polyglycol E200 (PEG-200) (50% w/w) was weighed and polyglycol E400 (PEG-400) (5% w/w) was added to the same container to obtain the desired weight, (both obtained from Dow Corning). PEG-200 and PEG-400 were lightning mixed at 38-40° C. with IKA model RW20 using a disintegration head impeller slowly at 800 rpm (speed 1), yielding PEG-200/PEG-400 solution. A PPC-enriched phosphatidylcholine material denoted NAT 8729 containing 80.6% PPC-enriched phosphatidylcholine and 4.9% lysophosphatidylcholine was obtained from Rhône-Poulenc. NAT 8729 (45% w/w) was shaved and added to PEG-200/PEG-400 solution, covered and mixed, with temperature not exceeding 40° C., until a clear, viscous amber solution with no sediments or separations resulted. The mixing time was approximately five hours. An alternative mixture can be prepared by covering and mixing the solution overnight without heat for a 95-96% yield. The solution was removed from heat and transferred to Ross Homogenizer (Model HSM100LC) using smallest mesh screen.
- A Dow Corning Fluid was then prepared. Dow Corning Fluid denominated 190 (1.00% w/w) [a siloxylated polyether comprising dimethyl, methyl(propylpolyethylene oxide propylene oxide, acetate) siloxane] and Dow Corning Fluid denoted 200-5 or 10 cst (1.00% w/w) [silicone fluids containing low viscosity polydimethylsiloxane polymers] were mixed together in a container with a clean spatula.
- The solution (53.25% w/w) was warmed to 40° C. and mixed at 800 rpm. Typical mixing times were approximately 5 hours. The solution was then milled at 3800 rpm and the Dow Corning Fluid mixture was added very slowly until a clear solution resulted. Methyl Paraben (p-hydroxy benzoic acid methyl ester) obtained from Mallinckrodt (0.75% w/w) was added at once and mixed until a complete solution resulted. Purified water warmed to 40° C. was added very slowly to solution while milling at 7500 rpm for about three minutes. At end of milling, speed was increased to 10,000 rpm for few seconds before stopping. The solution was removed and swept with paddle head using IKA Model RW-20 until cooled to room temperature. This step is very critical and if it is not done properly it will generate a biphasic end product. The general rule is to use a container having a volume twice that of the solution so the homogenizer head is well embedded in the solution. The solution was then cooled to room temperature.
- USP human recombinant insulin in obtained from Spectrum Chemicals and Laboratories (Product #11247) was prepared in 0.01 N HCl at 50 mg/ml, and gently, yet well mixed. This insulin preparation was then added very slowly to the above solution to obtain a final concentration of 500 units/ml or 20 mg/ml. Mixing was continued at room temperature for at least one hour. The final stable insulin composition was stored at 4° C. in amber air-tight container.
- RP-HPLC and HPCE analyses of insulin standards (prepared at 5 mg/ml in 0.01 N HCl) and stable insulin compositions of the invention which were stored at different temperatures for different periods of time were performed. The results indicated that standard insulin standards stored at 4° were stable up to 22 weeks and started to denature after 34 weeks, whereas when stored at room temperature started to denature within only 1 week. However, the stable insulin compositions prepared in accordance with the above disclosures that were stored at room temperature were stable up to at least 22 weeks, which is 21 weeks longer than the standard. The results showed no change in shelf-life from the standard for stable insulin compositions stored at 4° C. (no change after 34 weeks).
- Stable topical drug delivery compositions of the present invention may be employed to deliver and stabilize polypeptides transdermally, including but not limited to insulin, oxytocin, vasopressin, insulin, somatotropin, calcitonin, chorionic gonadotropin, menotropins, follitropins, somatostatins, progestins, and combinations of any of these. These drugs are readily available from a variety of commercial sources. Somatotropin (pituitary growth hormone) is marketed under the tradenames Gentropin®, Humatrope®, Nutropin®, and Serostim®.
- A drug delivery composition formulated with somatotropin was formulated in one trial with 85% phosphatidylcholine to which lipoic acid and ascorbyl palmitate were added. Somatotropin readily dispersed in phosphatidyl-choline and remained stable in it. Growth hormone appeared to penetrate the skin well when the composition was topically applied.
- The present invention may also be used to provide topical delivery of active agents other that drugs, for example, skin care agents. The invention is particularly useful with large molecules that are used in some cosmetic formulations, including peptides and polymers.
- The above description is for the purpose of teaching the person of ordinary skill in the art how to practice the present invention, and it is not intended to detail all those obvious modifications and variations of it which will become apparent to the skilled worker upon reading the description. It is intended, however, that all such obvious modifications and variations be included within the scope of the present invention
Claims (19)
1. A method for administering a polypeptide drug comprising:
applying a composition containing:
an effective amount of a polypeptide drug, and
a phosphatidylcholine and polyglycol multilamellar liquid crystal non-liposome carrier entrapping and stabilizing the polypeptide drug at room temperature;
to human skin whereby the carrier penetration the skin and delivers the polypeptide drug to the dermal vasculature.
2. The method of claim 1 , wherein said polyglycol comprises polyglycol having a molecular weight and polyglycol having a molecular weight of 400.
3. The method of claim 2 wherein weight percentages of said phosphatidylcholine and polyglycol are 45% w/w polyenylphosphatidylcholine, 50% w/w polyglycol having a molecular weight of 200, and 5% w/w polyglycol having a molecular weight of 400.
4. The method of claim 1 , wherein said carrier comprises a surfactant, a lubricant, and methyl paraben.
5. The method of claim 4 wherein said carrier comprises 97.25% w/w phosphatidylcholine and polyglycol, 1.00% w/w surfactant, 1.00% w/w lubricant, and 0.75% methyl paraben.
6. The method of claim 4 , wherein said carrier further comprises water.
7. The method of claim 6 , wherein said carrier comprises 53.25% w/w phosphatidylcholine and polyglycol, 1.00% w/w surfactant, 1.00% w/w lubricant, 0.75% w/w methyl paraben and 44% w/w water.
8. The method of claim 7 , wherein said surfactant is a siloxylated polyether.
9. The method of claim 8 , wherein said siloxylated polyether is dimethyl, methyl(propylpolyethylene oxide propylene oxide, acetate) siloxane.
10. The method of claim 4 , wherein said lubricant is silicone fluid.
11. The method of claim 10 , wherein said silicone fluid contains low viscosity polydimethylsiloxane polymers.
12. The method of claim 1 , wherein said drug is selected from the group consisting of oxytocin, vasopressin, insulin, somatotropin, calcitonin, chorionic gonadotropin, menotropins, follitropins, somatostatins, progestins, and combinations of any of these.
13. A method for administering a drug comprising:
applying a composition containing:
an effective amount of a drug, and
a phosphatidylcholine and polyglycol multilamellar liquid crystal non-liposome carrier entrapping and stabilizing the drug at room temperature;
to human skin whereby the carrier penetration the skin and delivers the drug to dermal vasculature in the human skin.
14. A method for administering a drug comprising:
applying a composition containing:
an effective amount of a drug, and
a phosphatidylcholine based multilamellar liquid crystal non-liposome carrier entrapping and stabilizing the drug at room temperature;
to human skin whereby the carrier penetration the skin and delivers the drug to dermal vasculature in the human skin.
15. The method of claim 14 , wherein said hosphatidylcholine based multilamellar liquid crystal non-liposome carrier further comprises polyglycol.
16. The method of claim 15 , wherein said polyglycol comprises polyglycol having a molecular weight and polyglycol having a molecular weight of 400.
17. The method of claim 15 wherein weight percentages of said phosphatidylcholine and polyglycol are 45% w/w polyenylphosphatidylcholine, 50% w/w polyglycol having a molecular weight of 200, and 5% w/w polyglycol having a molecular weight of 400.
18. The method of claim 15 , wherein said carrier comprises a surfactant, a lubricant, and methyl paraben.
19. The method of claim 15 , wherein said drug is selected from the group consisting of oxytocin, vasopressin, insulin, somatotropin, calcitonin, chorionic gonadotropin, menotropins, follitropins, somatostatins, progestins, and combinations of any of these.
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/019,101 US20110123577A1 (en) | 2002-05-31 | 2011-02-01 | Method Of Delivering Stable Topical Drug Compositions |
US13/947,353 US9050248B2 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US13/947,329 US9060925B2 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US13/947,389 US20130330381A1 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US14/705,023 US20150238608A1 (en) | 2002-05-31 | 2015-05-06 | Methods of delivering stable topical drug compositions |
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US38459702P | 2002-05-31 | 2002-05-31 | |
US43727902P | 2002-12-31 | 2002-12-31 | |
US10/448,632 US20040018237A1 (en) | 2002-05-31 | 2003-05-30 | Topical drug delivery using phosphatidylcholine |
US10/749,914 US7182956B2 (en) | 2002-05-31 | 2003-12-31 | Stable topical drug delivery compositions |
US11/334,206 US20060105955A1 (en) | 2002-05-31 | 2006-01-18 | Topical drug delivery using phosphatidylcholine |
US11/344,442 US20060127469A1 (en) | 2002-05-31 | 2006-01-31 | Methods of delivering stable topical drug compositions |
US13/019,101 US20110123577A1 (en) | 2002-05-31 | 2011-02-01 | Method Of Delivering Stable Topical Drug Compositions |
Related Parent Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/334,206 Continuation-In-Part US20060105955A1 (en) | 2002-05-31 | 2006-01-18 | Topical drug delivery using phosphatidylcholine |
US11/334,206 Continuation US20060105955A1 (en) | 2002-05-31 | 2006-01-18 | Topical drug delivery using phosphatidylcholine |
US11/344,442 Continuation US20060127469A1 (en) | 2002-05-31 | 2006-01-31 | Methods of delivering stable topical drug compositions |
Related Child Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/947,389 Continuation US20130330381A1 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US13/947,329 Continuation US9060925B2 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US13/947,353 Continuation US9050248B2 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
Publications (1)
Publication Number | Publication Date |
---|---|
US20110123577A1 true US20110123577A1 (en) | 2011-05-26 |
Family
ID=29715338
Family Applications (14)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/448,632 Abandoned US20040018237A1 (en) | 2002-05-31 | 2003-05-30 | Topical drug delivery using phosphatidylcholine |
US10/749,914 Expired - Fee Related US7182956B2 (en) | 2002-05-31 | 2003-12-31 | Stable topical drug delivery compositions |
US11/334,206 Abandoned US20060105955A1 (en) | 2002-05-31 | 2006-01-18 | Topical drug delivery using phosphatidylcholine |
US11/344,442 Abandoned US20060127469A1 (en) | 2002-05-31 | 2006-01-31 | Methods of delivering stable topical drug compositions |
US11/506,137 Abandoned US20060275353A1 (en) | 2002-05-31 | 2006-08-17 | Stable topical drug delivery compositions |
US12/830,857 Abandoned US20100292139A1 (en) | 2002-05-31 | 2010-07-06 | Topical drug delivery using phosphatidylcholine |
US13/019,101 Abandoned US20110123577A1 (en) | 2002-05-31 | 2011-02-01 | Method Of Delivering Stable Topical Drug Compositions |
US13/024,689 Expired - Lifetime US8273711B2 (en) | 2002-05-31 | 2011-02-10 | Topical drug delivery using phosphatidylcholine |
US13/926,688 Abandoned US20130330380A1 (en) | 2002-05-31 | 2013-06-25 | Topical drug delivery using phosphatidylcholine |
US13/947,329 Expired - Fee Related US9060925B2 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US13/947,353 Expired - Fee Related US9050248B2 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US13/947,389 Abandoned US20130330381A1 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US14/296,634 Abandoned US20150004196A1 (en) | 2002-05-31 | 2014-06-05 | Topical drug delivery using phosphatidylcholine |
US14/705,023 Abandoned US20150238608A1 (en) | 2002-05-31 | 2015-05-06 | Methods of delivering stable topical drug compositions |
Family Applications Before (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/448,632 Abandoned US20040018237A1 (en) | 2002-05-31 | 2003-05-30 | Topical drug delivery using phosphatidylcholine |
US10/749,914 Expired - Fee Related US7182956B2 (en) | 2002-05-31 | 2003-12-31 | Stable topical drug delivery compositions |
US11/334,206 Abandoned US20060105955A1 (en) | 2002-05-31 | 2006-01-18 | Topical drug delivery using phosphatidylcholine |
US11/344,442 Abandoned US20060127469A1 (en) | 2002-05-31 | 2006-01-31 | Methods of delivering stable topical drug compositions |
US11/506,137 Abandoned US20060275353A1 (en) | 2002-05-31 | 2006-08-17 | Stable topical drug delivery compositions |
US12/830,857 Abandoned US20100292139A1 (en) | 2002-05-31 | 2010-07-06 | Topical drug delivery using phosphatidylcholine |
Family Applications After (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/024,689 Expired - Lifetime US8273711B2 (en) | 2002-05-31 | 2011-02-10 | Topical drug delivery using phosphatidylcholine |
US13/926,688 Abandoned US20130330380A1 (en) | 2002-05-31 | 2013-06-25 | Topical drug delivery using phosphatidylcholine |
US13/947,329 Expired - Fee Related US9060925B2 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US13/947,353 Expired - Fee Related US9050248B2 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US13/947,389 Abandoned US20130330381A1 (en) | 2002-05-31 | 2013-07-22 | Methods of delivering stable topical drug compositions |
US14/296,634 Abandoned US20150004196A1 (en) | 2002-05-31 | 2014-06-05 | Topical drug delivery using phosphatidylcholine |
US14/705,023 Abandoned US20150238608A1 (en) | 2002-05-31 | 2015-05-06 | Methods of delivering stable topical drug compositions |
Country Status (10)
Country | Link |
---|---|
US (14) | US20040018237A1 (en) |
EP (1) | EP1509243B1 (en) |
JP (1) | JP2005531595A (en) |
CN (1) | CN100509054C (en) |
AU (1) | AU2003231943B2 (en) |
CA (1) | CA2487305A1 (en) |
ES (1) | ES2632912T3 (en) |
HK (1) | HK1083009A1 (en) |
IL (2) | IL165480A0 (en) |
WO (1) | WO2003101480A1 (en) |
Cited By (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060275353A1 (en) * | 2002-05-31 | 2006-12-07 | Nicholas V. Perricone | Stable topical drug delivery compositions |
US8668937B2 (en) | 2011-03-17 | 2014-03-11 | Transdermal Biotechnology, Inc. | Topical nitric oxide systems and methods of use thereof |
US8871256B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Methods and systems for treatment of inflammatory diseases with nitric oxide |
US8871259B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Techniques and systems for treatment of neuropathic pain and other indications |
US8871258B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Treatment and prevention of learning and memory disorders |
US8871260B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Methods and compositions for muscular and neuromuscular diseases |
US8871257B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Prevention and treatment of cardiovascular diseases using systems and methods for transdermal nitric oxide delivery |
US8871262B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Compositions and methods for treatment of osteoporosis and other indications |
US8871261B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Cancer treatments and compositions for use thereof |
US8871254B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Systems and methods for treatment of acne vulgaris and other conditions with a topical nitric oxide delivery system |
US8871255B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Treatment of skin and soft tissue infection with nitric oxide |
US9241899B2 (en) | 2013-03-13 | 2016-01-26 | Transdermal Biotechnology, Inc. | Topical systems and methods for treating sexual dysfunction |
US9295636B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US9295637B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Compositions and methods for affecting mood states |
US9295647B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US9314422B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9314433B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
US9314417B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9314423B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Hair treatment systems and methods using peptides and other compositions |
US9320706B2 (en) | 2013-03-13 | 2016-04-26 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
US9320758B2 (en) | 2013-03-13 | 2016-04-26 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
US9339457B2 (en) | 2013-03-13 | 2016-05-17 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US9387159B2 (en) | 2013-03-13 | 2016-07-12 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9393264B2 (en) | 2013-03-13 | 2016-07-19 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
US9393265B2 (en) | 2013-03-13 | 2016-07-19 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US9585931B2 (en) | 2013-03-13 | 2017-03-07 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US9597401B2 (en) | 2013-03-13 | 2017-03-21 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US9597400B2 (en) | 2013-03-13 | 2017-03-21 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9687520B2 (en) | 2013-03-13 | 2017-06-27 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
US9849160B2 (en) | 2013-03-13 | 2017-12-26 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
US10034914B2 (en) | 2013-03-13 | 2018-07-31 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
US10226511B2 (en) | 2013-03-13 | 2019-03-12 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002950713A0 (en) | 2002-08-09 | 2002-09-12 | Vital Health Sciences Pty Ltd | Carrier |
JP5221343B2 (en) | 2005-06-17 | 2013-06-26 | バイタル ヘルス サイエンシズ プロプライアタリー リミティド | Carrier |
US20070148222A1 (en) * | 2005-12-28 | 2007-06-28 | Discovery Partners Llc | Skin treatment compositions containing copper-pigment complexes |
US20070148224A1 (en) * | 2005-12-28 | 2007-06-28 | Discovery Partners Llc | Skin treatment compositions containing copper-pigment complexes |
EP2076274A4 (en) * | 2006-09-11 | 2010-08-04 | Biomas Ltd | Topical formulations of tellurium-containing compounds |
US20080317836A1 (en) * | 2007-06-19 | 2008-12-25 | Discovery Partners Llc | Topical compositions for anti-aging skin treatment |
US20100068275A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Personalizable dosage form |
US20100068233A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Modifiable dosage form |
US20100069821A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Ex vivo modifiable medicament release-sites final dosage form |
US8753677B2 (en) * | 2008-09-16 | 2014-06-17 | The Invention Science Fund I, Llc | Ex vivo modifiable multiple medicament final dosage form |
US20100068254A1 (en) * | 2008-09-16 | 2010-03-18 | Mahalaxmi Gita Bangera | Modifying a medicament availability state of a final dosage form |
US20100068153A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Ex vivo activatable final dosage form |
US20100068235A1 (en) * | 2008-09-16 | 2010-03-18 | Searete LLC, a limited liability corporation of Deleware | Individualizable dosage form |
US20100068152A1 (en) * | 2008-09-16 | 2010-03-18 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Ex vivo modifiable particle or polymeric based final dosage form |
FR2950807B1 (en) * | 2009-10-06 | 2012-02-03 | Lvmh Rech | COSMETIC COMPOSITION CONTAINING LIPOSOMES ENCAPSULATED IN OXAZOLIDIN-2-ONE COMPOUND |
EP2531047A4 (en) | 2010-02-05 | 2014-03-19 | Phosphagenics Ltd | Carrier comprising non-neutralised tocopheryl phosphate |
AU2011235597B2 (en) | 2010-03-30 | 2015-07-16 | Phosphagenics Limited | Transdermal delivery patch |
WO2011152832A1 (en) | 2010-06-04 | 2011-12-08 | N.V. Perricone Llc | Methods of use of nitroalkene compositions in dermatologic applications to prevent or treat skin aging |
US20120207838A1 (en) * | 2011-02-10 | 2012-08-16 | Perricone Nicholas V | Treatment of Psoriasis Using Oral Dosage Forms of Nitrone Spin Traps |
US8986739B2 (en) * | 2011-02-28 | 2015-03-24 | Nicholas V. Perricone | Treatment of urinary incontinence using nitrone spin traps |
WO2012122586A1 (en) | 2011-03-15 | 2012-09-20 | Phosphagenics Limited | New composition |
KR101943508B1 (en) | 2011-07-21 | 2019-01-30 | (주)아모레퍼시픽 | Cosmetic compositions having relaxing effect of fatigued muscle |
US20160136169A1 (en) * | 2012-09-19 | 2016-05-19 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of tetrahydrobiopterin and related compounds |
US20140271742A1 (en) * | 2013-03-13 | 2014-09-18 | Transdermal Biotechnology, Inc. | Skin tanning using peptides and other compositions |
US11484534B2 (en) | 2013-03-14 | 2022-11-01 | Abbvie Inc. | Methods for treating HCV |
CN112891511A (en) | 2014-04-02 | 2021-06-04 | 艾伯维公司 | Methods of treating HCV |
US9707266B2 (en) | 2014-11-18 | 2017-07-18 | Transdermal Biotechnology, Inc. | Methods and systems for delivery of ZW1 heptapeptide |
US20160375017A1 (en) | 2015-06-26 | 2016-12-29 | Abbvie Inc. | Solid Pharmaceutical Compositions for Treating HCV |
JP6882321B2 (en) | 2015-12-09 | 2021-06-02 | フォスファージニクス リミテッド | Pharmaceutical product |
EP3463304A4 (en) * | 2016-05-24 | 2020-01-08 | Bol Pharma Ltd. | Compositions comprising cannabidiol and hyaluronic acid for treating inflammatory joint diseases |
US9949939B2 (en) | 2016-07-01 | 2018-04-24 | Transdermal Biotechnology, Inc. | Systems and methods for treating vitiligo |
CN110662733A (en) | 2016-12-21 | 2020-01-07 | 埃维科生物技术有限公司 | Method of producing a composite material |
WO2019150594A1 (en) * | 2018-01-31 | 2019-08-08 | 株式会社ユニッシュ | Transdermal phosphatidylcholine preparation |
WO2022192135A1 (en) * | 2021-03-08 | 2022-09-15 | Transdermal Biotechnology, Inc. | Dendrimer-n-actyl-l-cysteine conjugates for treatment or prevention of aging skin or other indications |
WO2022221376A1 (en) | 2021-04-14 | 2022-10-20 | Transdermal Biotechnology, Inc. | Systems and methods for treating vitiligo using ethyl pyruvate and other compounds |
Citations (77)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4174296A (en) * | 1978-12-04 | 1979-11-13 | American Lecithin Company | Water soluble lecithin composition |
US4333927A (en) * | 1980-03-27 | 1982-06-08 | Mitsubishi Chemical Industries, Ltd. | Skin preparation |
US4614730A (en) * | 1981-10-30 | 1986-09-30 | Novo Industri A/S | Stabilized insulin preparations and a process for preparation thereof |
US4624665A (en) * | 1984-10-01 | 1986-11-25 | Biotek, Inc. | Method of transdermal drug delivery |
US4657661A (en) * | 1985-12-11 | 1987-04-14 | Chevron Research Company | Process for improving the storage stability and bulk oxidation stability of lube base stocks derived from bright stock |
US4708861A (en) * | 1984-02-15 | 1987-11-24 | The Liposome Company, Inc. | Liposome-gel compositions |
US4743449A (en) * | 1983-09-12 | 1988-05-10 | Fujisawa Pharmaceutical Co., Ltd. | Drug-containing lipid vesicle preparation and method for preparing them |
US5120561A (en) * | 1991-04-25 | 1992-06-09 | American Lecithin Company | Food composition and method |
US5151272A (en) * | 1982-11-26 | 1992-09-29 | Fluid-Carbon International Ab | Method of preparing controlled-release preparations for biologically active materials and resulting compositions |
US5153000A (en) * | 1988-11-22 | 1992-10-06 | Kao Corporation | Phosphate, liposome comprising the phosphate as membrane constituent, and cosmetic and liposome preparation comprising the liposome |
US5206219A (en) * | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
US5254348A (en) * | 1990-01-26 | 1993-10-19 | Lts Lohmann Therapie Systeme Gmbh & Co. Kg | Transdermal therapeutic system comprising tulobuterol as active substance |
US5308625A (en) * | 1992-09-02 | 1994-05-03 | Cygnus Therapeutic Systems | Enhancement of transdermal drug delivery using monoalkyl phosphates and other absorption promoters |
US5380761A (en) * | 1991-04-15 | 1995-01-10 | Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt. | Transdermal compositions |
US5391548A (en) * | 1986-10-31 | 1995-02-21 | Pfizer Inc. | Transdermal flux enhancing compositions to treat hypertension, diabetes and angina pectoris |
US5439967A (en) * | 1991-09-17 | 1995-08-08 | Micro Vesicular Systems, Inc. | Propylene glycol stearate vesicles |
US5476651A (en) * | 1991-05-22 | 1995-12-19 | Lvmh Recherche | Cosmetic or pharmaceutical composition, especially dermatological composition, intended for promoting the pigmentation of the skin or hair, containing an extract of cyperus, and the process for its manufacture |
US5484816A (en) * | 1992-07-13 | 1996-01-16 | Shiseido Company, Ltd. | External skin treatment composition |
US5504117A (en) * | 1994-05-27 | 1996-04-02 | Neptune Pharmaceutical Corporation | Pharmacologic preparation for the treatment of anal disorders |
US5550263A (en) * | 1991-06-03 | 1996-08-27 | Karlshamns Lipidteknik Ab | X-ray contrast agent |
US5576016A (en) * | 1993-05-18 | 1996-11-19 | Pharmos Corporation | Solid fat nanoemulsions as drug delivery vehicles |
US5656286A (en) * | 1988-03-04 | 1997-08-12 | Noven Pharmaceuticals, Inc. | Solubility parameter based drug delivery system and method for altering drug saturation concentration |
US5674912A (en) * | 1991-03-01 | 1997-10-07 | Warner-Lambert Company | Sunscreen-wound healing compositions and methods for preparing and using same |
US5693676A (en) * | 1994-05-27 | 1997-12-02 | Neptune Pharmaceutical Corporation | Nitric oxide donor composition and method for treatment of anal disorders |
US5726164A (en) * | 1995-03-21 | 1998-03-10 | Novartis Corporation | Nanosuspensions for intravenous administration |
US5776494A (en) * | 1996-12-20 | 1998-07-07 | The Procter & Gamble Company | Pharmaceuticals compositions containing gellants in the form of alkyl amides of di-and tri-carboxylic acids |
US5807573A (en) * | 1994-06-15 | 1998-09-15 | Gs Development Ab | Lipid based composition containing diacylglycerol, phospholipid, polar liquid and biologically active material |
US5814666A (en) * | 1992-04-13 | 1998-09-29 | The United States As Represented By The Department Of Health And Human Services | Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents |
US5853755A (en) * | 1993-07-28 | 1998-12-29 | Pharmaderm Laboratories Ltd. | Biphasic multilamellar lipid vesicles |
US5858398A (en) * | 1994-11-03 | 1999-01-12 | Isomed Inc. | Microparticular pharmaceutical compositions |
US5869539A (en) * | 1996-04-17 | 1999-02-09 | Board Of Regents, The University Of Texas System | Emulsions of perfluoro compounds as solvents for nitric oxide (NO) |
US5874479A (en) * | 1991-03-01 | 1999-02-23 | Warner-Lambert Company | Therapeutic permeation enhanced-wound healing compositions and methods for preparing and using same |
US5879690A (en) * | 1995-09-07 | 1999-03-09 | Perricone; Nicholas V. | Topical administration of catecholamines and related compounds to subcutaneous muscle tissue using percutaneous penetration enhancers |
US5891472A (en) * | 1996-11-19 | 1999-04-06 | Meri Charmyne Russell | Treatment of equine laminitis |
US5955502A (en) * | 1994-03-30 | 1999-09-21 | Gs Development Ab | Use of fatty acid esters as bioadhesive substances |
US5976562A (en) * | 1994-02-01 | 1999-11-02 | Krall; Theodor | Process for producing bactericidal/fungicidal plastic bodies |
WO1999056725A1 (en) * | 1998-04-30 | 1999-11-11 | Ucb, S.A. | Pharmaceutical compositions capable of being gelled |
US5985298A (en) * | 1994-10-25 | 1999-11-16 | Revlon Consumer Products Corporation | Cosmetic compositions |
US6022561A (en) * | 1994-02-04 | 2000-02-08 | Scotia Lipidteknik Ab | Bilayers preparations |
US6103275A (en) * | 1998-06-10 | 2000-08-15 | Nitric Oxide Solutions | Systems and methods for topical treatment with nitric oxide |
US6133320A (en) * | 1996-03-19 | 2000-10-17 | Board Of Regents, The University Of Texas System | Treatment of osteoporosis and metabolic bone disorders with nitric oxide substrate and/or donors |
US6165500A (en) * | 1990-08-24 | 2000-12-26 | Idea Ag | Preparation for the application of agents in mini-droplets |
US6191121B1 (en) * | 2000-04-06 | 2001-02-20 | Nicholas V. Perricone | Treatment of skin damage using polyenylphosphatidylcholine |
US6193997B1 (en) * | 1998-09-27 | 2001-02-27 | Generex Pharmaceuticals Inc. | Proteinic drug delivery system using membrane mimetics |
US6207713B1 (en) * | 1997-09-17 | 2001-03-27 | Eric T. Fossel | Topical and oral delivery of arginine to cause beneficial effects |
US6211250B1 (en) * | 1996-11-22 | 2001-04-03 | Soltec Research Pty Ltd. | Percutaneous delivery system |
US6214375B1 (en) * | 1996-07-16 | 2001-04-10 | Generex Pharmaceuticals, Inc. | Phospholipid formulations |
US6242099B1 (en) * | 1996-11-21 | 2001-06-05 | Merck S.A. | Microcapsules made of chitin or of chitin derivatives containing a hydrophobic substance, in particular a sunscreen, and process for the preparation of such microcapsules |
US6294192B1 (en) * | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US6391869B1 (en) * | 1998-12-14 | 2002-05-21 | Cellergy Pharmaceuticals, Inc. | Compositions and methods for the treatment of anorectal disorders |
US20020131994A1 (en) * | 2001-01-10 | 2002-09-19 | Schur Henry B. | Non-irritating formulation for the transdermal delivery of substances |
US20020153509A1 (en) * | 2001-02-21 | 2002-10-24 | The Procter & Gamble Company | Functionalized cubic liquid crystalline phase materials and methods for their preparation and use |
US20020160040A1 (en) * | 2001-02-20 | 2002-10-31 | Spicer Patrick Thomas | Cubic liquid crystalline compositions and methods for their preparation |
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 |
US6521250B2 (en) * | 1993-05-06 | 2003-02-18 | Lts Lohmann Therapie-Systeme Gmbh | Transdermal therapeutic system containing estradiol |
US6538061B2 (en) * | 2001-05-16 | 2003-03-25 | General Electric Company | Cosmetic compositions using polyether siloxane copolymer network compositions |
US6555573B2 (en) * | 2000-12-21 | 2003-04-29 | The Quigley Corporation | Method and composition for the topical treatment of diabetic neuropathy |
US6568061B2 (en) * | 2001-09-21 | 2003-05-27 | Atlantic Research Corporation | Method for controlling composite preform elements during processing |
US20040018237A1 (en) * | 2002-05-31 | 2004-01-29 | Perricone Nicholas V. | Topical drug delivery using phosphatidylcholine |
US20040096494A1 (en) * | 2001-03-15 | 2004-05-20 | Britta Siekmann | Composition |
US6780849B2 (en) * | 2000-12-21 | 2004-08-24 | Scimed Life Systems, Inc. | Lipid-based nitric oxide donors |
US20040191305A1 (en) * | 2002-05-31 | 2004-09-30 | Perricone Nicholas V. | Methods for formulating stabilized insulin compositions |
US6932963B2 (en) * | 2000-06-23 | 2005-08-23 | Nicholas V. Perricone | Treatment of skin wounds using polyenylphosphatidylcholine and alkanolamines |
US6936044B2 (en) * | 1998-11-30 | 2005-08-30 | Light Bioscience, Llc | Method and apparatus for the stimulation of hair growth |
US20050226945A1 (en) * | 2004-04-13 | 2005-10-13 | Ruwart Mary J | Compositions and methods for the treatment of radiation burns and other traumatic skin conditions |
US7033574B1 (en) * | 1990-04-02 | 2006-04-25 | Bracco International B.V. | Stable microbubbles suspensions injectable into living organisms |
US20090214624A1 (en) * | 2004-11-29 | 2009-08-27 | The University Of Akron | Topical nitric oxide donor devices and methods for their therapeutic use |
US20090304815A1 (en) * | 2006-02-03 | 2009-12-10 | Giulio Cossu | Method of treatment for muscular dystrophy |
US20090324698A1 (en) * | 2004-10-18 | 2009-12-31 | Polymun Scientific Immunbiologische Forschung Gmbh | Liposomal composition comprising an active ingredient for relaxing smooth muscle, the production of this composition and the therapeutic use thereof |
US20100048520A1 (en) * | 2006-03-09 | 2010-02-25 | Salix Pharmaceuticals, Ltd. | Rifaximin anti-rectal dysfunction preparation |
US7820420B2 (en) * | 2000-08-11 | 2010-10-26 | Whitlock David R | Compositions including ammonia oxidizing bacteria to increase production of nitric oxide and nitric oxide precursors and methods of using same |
US20100311696A1 (en) * | 2002-05-31 | 2010-12-09 | Perricone Nicholas V | Topical skin treatment composition |
US20110104240A1 (en) * | 2008-06-24 | 2011-05-05 | Micropharma Limited | Nitric Oxide Device and Method for Wound Healing, Treatment of Dermatological Disorders and Microbial Infections |
US7976743B2 (en) * | 2006-10-16 | 2011-07-12 | Northwestern University | Gas-containing liposomes |
US20120156163A1 (en) * | 2010-12-15 | 2012-06-21 | Susanne Bauman | Methods of decreasing sebum production in the skin |
US20130029989A1 (en) * | 2010-04-15 | 2013-01-31 | The Royal Institution For The Advancement Of Learning/Mcgill University | Topical treatments for pain |
US20130059017A1 (en) * | 2011-03-17 | 2013-03-07 | Transdermal Biotechinology, Inc. | Topical nitric oxide systems and methods of use thereof |
Family Cites Families (84)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US561330A (en) * | 1896-06-02 | ljungstrom | ||
US482554A (en) * | 1892-09-13 | Joseph galland | ||
US722323A (en) * | 1900-03-26 | 1903-03-10 | Benjamin W Parker | Letter-box. |
US727323A (en) * | 1901-10-04 | 1903-05-05 | Harry Feder | Dress-stay blank. |
US2181390A (en) * | 1933-08-09 | 1939-11-28 | Arthur M Barrett | Easel |
US2182390A (en) * | 1937-01-13 | 1939-12-05 | William F Reardon | Surgical device |
US4251861A (en) * | 1978-10-27 | 1981-02-17 | Mago Gyula A | Cellular network of processors |
GB2134869A (en) * | 1983-02-15 | 1984-08-22 | Squibb & Sons Inc | Method of preparing liposomes and products produced thereby |
JPS607932A (en) * | 1983-06-29 | 1985-01-16 | Dai Ichi Seiyaku Co Ltd | Preparation of liposome |
JPS60155109A (en) * | 1984-01-23 | 1985-08-15 | Terumo Corp | Liposome pharmaceutical |
JPS6176414A (en) * | 1984-09-21 | 1986-04-18 | Shionogi & Co Ltd | Production of liposome preparation |
EP0256119A4 (en) | 1986-02-10 | 1988-08-23 | Liposome Technology Inc | Controlled-release liposome delivery system. |
US4833468A (en) * | 1987-10-14 | 1989-05-23 | Unisys Corporation | Layered network |
US5223476A (en) | 1989-05-02 | 1993-06-29 | Dai Nippon Insatsu Kabushiki Kaisha | Heat transfer sheet |
JP3765579B2 (en) * | 1990-08-24 | 2006-04-12 | イーデーエーアー アーゲー | Ultra-fine droplet preparation for active substance administration |
CA2053462A1 (en) | 1990-10-22 | 1992-04-23 | Yoshiaki Yano | Sticky composition for medical use |
ATE182278T1 (en) * | 1991-10-04 | 1999-08-15 | Gs Dev Ab | PARTICLES, METHOD FOR PRODUCING THE PARTICLES AND THEIR USE |
DE4208552A1 (en) | 1992-03-17 | 1993-09-23 | Liedtke Pharmed Gmbh | TOPICAL MEDICINE FORMS WITH INSULIN |
US5555405A (en) * | 1993-07-06 | 1996-09-10 | Digital Equipment Corporation | Method and apparatus for free space management in a forwarding database having forwarding entry sets and multiple free space segment queues |
ES2100082T3 (en) * | 1993-07-07 | 1997-06-01 | Europ Computer Ind Res | STRUCTURES OF DATABASES. |
FI100692B (en) * | 1994-05-24 | 1998-02-13 | Leiras Oy | A process for the preparation of pharmaceutical compositions, wherein the compositions are based on microemulsion gels and new gels directed to microemulsions. |
DE69422935T2 (en) * | 1994-06-30 | 2000-08-17 | Ibm | METHOD AND DEVICE FOR COMPARING VARIABLE LENGTH DATA SEQUENCES |
ES2141950T3 (en) | 1994-08-05 | 2000-04-01 | Inpharma Sa | COMPOSITIONS CONTAINING TROXERUTINE COMPLEXED WITH PHOSFATIDYLCHOLINE FOR THE TOPICAL TREATMENT OF ERECTILE IMPOTENCE. |
US5761440A (en) * | 1994-09-15 | 1998-06-02 | International Business Machines Corporation | System and method utilizing multiple search trees to route data within a data processing network |
US5707641A (en) * | 1994-10-13 | 1998-01-13 | Pharmaderm Research & Development Ltd. | Formulations comprising therapeutically-active proteins or polypeptides |
CA2181390C (en) | 1995-07-18 | 2001-04-24 | Pankaj Modi | Phospholipid formulations |
DE19640092A1 (en) * | 1996-09-28 | 1998-04-16 | Beiersdorf Ag | Structures with lipid double membranes, in the lipophilic area of which longer-chain molecules are immersed or which are docked to such molecules through hydrophobic interactions |
US5909440A (en) * | 1996-12-16 | 1999-06-01 | Juniper Networks | High speed variable length best match look-up in a switching device |
JPH10194994A (en) | 1997-01-16 | 1998-07-28 | Pola Chem Ind Inc | Absorption acceleration composition |
US6021131A (en) * | 1997-07-08 | 2000-02-01 | Lucent Technologies, Inc. | Sorting networks having enhanced layout |
JPH1179975A (en) | 1997-09-05 | 1999-03-23 | Mitsui Chem Inc | Preparation of microcapsule |
US6018524A (en) * | 1997-09-09 | 2000-01-25 | Washington University | Scalable high speed IP routing lookups |
US6266706B1 (en) * | 1997-09-15 | 2001-07-24 | Effnet Group Ab | Fast routing lookup system using complete prefix tree, bit vector, and pointers in a routing table for determining where to route IP datagrams |
US6041053A (en) * | 1997-09-18 | 2000-03-21 | Microsfot Corporation | Technique for efficiently classifying packets using a trie-indexed hierarchy forest that accommodates wildcards |
US6563823B1 (en) * | 1997-10-30 | 2003-05-13 | Marconi Communications, Inc. | Multi-resolution tree for longest match address lookups |
US6061712A (en) * | 1998-01-07 | 2000-05-09 | Lucent Technologies, Inc. | Method for IP routing table look-up |
US6289013B1 (en) * | 1998-02-09 | 2001-09-11 | Lucent Technologies, Inc. | Packet filter method and apparatus employing reduced memory |
US6341130B1 (en) * | 1998-02-09 | 2002-01-22 | Lucent Technologies, Inc. | Packet classification method and apparatus employing two fields |
US6092072A (en) * | 1998-04-07 | 2000-07-18 | Lucent Technologies, Inc. | Programmed medium for clustering large databases |
US6522632B1 (en) * | 1998-05-06 | 2003-02-18 | Avici Systems | Apparatus and method for efficient prefix search |
US6157955A (en) * | 1998-06-15 | 2000-12-05 | Intel Corporation | Packet processing system including a policy engine having a classification unit |
US6560229B1 (en) * | 1998-07-08 | 2003-05-06 | Broadcom Corporation | Network switching architecture with multiple table synchronization, and forwarding of both IP and IPX packets |
US6212184B1 (en) * | 1998-07-15 | 2001-04-03 | Washington University | Fast scaleable methods and devices for layer four switching |
JP2000086501A (en) | 1998-09-11 | 2000-03-28 | Sankyo Co Ltd | Liposome formulation of human calcitonin |
AU5409699A (en) | 1999-07-05 | 2001-01-22 | Idea Ag | A method for the improvement of transport across adaptable semi-permeable barriers |
JP2003520210A (en) | 2000-01-05 | 2003-07-02 | イマレックス セラピューティクス, インコーポレイテッド | Pharmaceutical formulations for delivery of drugs with low water solubility |
US6581106B1 (en) * | 2000-01-13 | 2003-06-17 | Pierluigi Crescenzi | Fast address lookup in routing tables |
ATE319249T1 (en) * | 2000-01-27 | 2006-03-15 | Ibm | METHOD AND DEVICE FOR CLASSIFICATION OF DATA PACKETS |
BR0005797A (en) * | 2000-03-20 | 2001-10-16 | Abbott Lab | Methods for the treatment of sexual dysfunction with apomorphine at specified plasma concentration levels |
KR100508695B1 (en) | 2001-02-13 | 2005-08-17 | 한국과학기술연구원 | Formulation for oral delivery of insulin and preparation method thereof |
KR20020066778A (en) | 2001-02-13 | 2002-08-21 | 한국과학기술연구원 | Formulation to enhance bioavailability of bioactive materials and preparation method thereof |
US6858398B2 (en) * | 2001-08-14 | 2005-02-22 | Immunosciences Lab., Inc. | Saliva test for detection of food allergy and intolerance |
ES2362412T3 (en) | 2002-12-31 | 2011-07-05 | Transdermal Biotechnology, Inc. | STABLE COMPOSITIONS FOR THE TOPICAL SUPPLY OF DRUGS. |
US8871258B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Treatment and prevention of learning and memory disorders |
US8871260B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Methods and compositions for muscular and neuromuscular diseases |
US8871262B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Compositions and methods for treatment of osteoporosis and other indications |
US8871261B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Cancer treatments and compositions for use thereof |
US8871257B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Prevention and treatment of cardiovascular diseases using systems and methods for transdermal nitric oxide delivery |
US8871256B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Methods and systems for treatment of inflammatory diseases with nitric oxide |
US8871259B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Techniques and systems for treatment of neuropathic pain and other indications |
US8871255B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Treatment of skin and soft tissue infection with nitric oxide |
US8871254B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Systems and methods for treatment of acne vulgaris and other conditions with a topical nitric oxide delivery system |
US20140271731A1 (en) | 2013-03-13 | 2014-09-18 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US20140271938A1 (en) | 2013-03-13 | 2014-09-18 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US9849160B2 (en) | 2013-03-13 | 2017-12-26 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
US9295647B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US9314422B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9750787B2 (en) | 2013-03-13 | 2017-09-05 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
US9314423B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Hair treatment systems and methods using peptides and other compositions |
US9295636B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US20140271937A1 (en) | 2013-03-13 | 2014-09-18 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
US9295637B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Compositions and methods for affecting mood states |
US9393264B2 (en) | 2013-03-13 | 2016-07-19 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
US9387159B2 (en) | 2013-03-13 | 2016-07-12 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9314417B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9724419B2 (en) | 2013-03-13 | 2017-08-08 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9339457B2 (en) | 2013-03-13 | 2016-05-17 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US9687520B2 (en) | 2013-03-13 | 2017-06-27 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
US9241899B2 (en) | 2013-03-13 | 2016-01-26 | Transdermal Biotechnology, Inc. | Topical systems and methods for treating sexual dysfunction |
US9320758B2 (en) | 2013-03-13 | 2016-04-26 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
US9314433B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
US9393265B2 (en) | 2013-03-13 | 2016-07-19 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US20140271742A1 (en) | 2013-03-13 | 2014-09-18 | Transdermal Biotechnology, Inc. | Skin tanning using peptides and other compositions |
US9320706B2 (en) | 2013-03-13 | 2016-04-26 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
-
2003
- 2003-05-30 US US10/448,632 patent/US20040018237A1/en not_active Abandoned
- 2003-06-02 AU AU2003231943A patent/AU2003231943B2/en not_active Ceased
- 2003-06-02 CA CA002487305A patent/CA2487305A1/en not_active Withdrawn
- 2003-06-02 WO PCT/US2003/017220 patent/WO2003101480A1/en active Application Filing
- 2003-06-02 JP JP2004508835A patent/JP2005531595A/en active Pending
- 2003-06-02 CN CNB038180278A patent/CN100509054C/en not_active Expired - Fee Related
- 2003-06-02 ES ES03756329.3T patent/ES2632912T3/en not_active Expired - Lifetime
- 2003-06-02 IL IL16548003A patent/IL165480A0/en unknown
- 2003-06-02 EP EP03756329.3A patent/EP1509243B1/en not_active Expired - Lifetime
- 2003-12-31 US US10/749,914 patent/US7182956B2/en not_active Expired - Fee Related
-
2004
- 2004-11-30 IL IL165480A patent/IL165480A/en active IP Right Grant
-
2006
- 2006-01-18 US US11/334,206 patent/US20060105955A1/en not_active Abandoned
- 2006-01-31 US US11/344,442 patent/US20060127469A1/en not_active Abandoned
- 2006-03-09 HK HK06103057A patent/HK1083009A1/en not_active IP Right Cessation
- 2006-08-17 US US11/506,137 patent/US20060275353A1/en not_active Abandoned
-
2010
- 2010-07-06 US US12/830,857 patent/US20100292139A1/en not_active Abandoned
-
2011
- 2011-02-01 US US13/019,101 patent/US20110123577A1/en not_active Abandoned
- 2011-02-10 US US13/024,689 patent/US8273711B2/en not_active Expired - Lifetime
-
2013
- 2013-06-25 US US13/926,688 patent/US20130330380A1/en not_active Abandoned
- 2013-07-22 US US13/947,329 patent/US9060925B2/en not_active Expired - Fee Related
- 2013-07-22 US US13/947,353 patent/US9050248B2/en not_active Expired - Fee Related
- 2013-07-22 US US13/947,389 patent/US20130330381A1/en not_active Abandoned
-
2014
- 2014-06-05 US US14/296,634 patent/US20150004196A1/en not_active Abandoned
-
2015
- 2015-05-06 US US14/705,023 patent/US20150238608A1/en not_active Abandoned
Patent Citations (96)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4174296A (en) * | 1978-12-04 | 1979-11-13 | American Lecithin Company | Water soluble lecithin composition |
US4333927A (en) * | 1980-03-27 | 1982-06-08 | Mitsubishi Chemical Industries, Ltd. | Skin preparation |
US4614730A (en) * | 1981-10-30 | 1986-09-30 | Novo Industri A/S | Stabilized insulin preparations and a process for preparation thereof |
US5151272A (en) * | 1982-11-26 | 1992-09-29 | Fluid-Carbon International Ab | Method of preparing controlled-release preparations for biologically active materials and resulting compositions |
US5753259A (en) * | 1982-11-26 | 1998-05-19 | Gs Development Ab | Method of preparing controlled-release preparations for biologically active materials and resulting compositions |
US4743449A (en) * | 1983-09-12 | 1988-05-10 | Fujisawa Pharmaceutical Co., Ltd. | Drug-containing lipid vesicle preparation and method for preparing them |
US4708861A (en) * | 1984-02-15 | 1987-11-24 | The Liposome Company, Inc. | Liposome-gel compositions |
US4624665A (en) * | 1984-10-01 | 1986-11-25 | Biotek, Inc. | Method of transdermal drug delivery |
US4657661A (en) * | 1985-12-11 | 1987-04-14 | Chevron Research Company | Process for improving the storage stability and bulk oxidation stability of lube base stocks derived from bright stock |
US5391548A (en) * | 1986-10-31 | 1995-02-21 | Pfizer Inc. | Transdermal flux enhancing compositions to treat hypertension, diabetes and angina pectoris |
US5656286A (en) * | 1988-03-04 | 1997-08-12 | Noven Pharmaceuticals, Inc. | Solubility parameter based drug delivery system and method for altering drug saturation concentration |
US5153000A (en) * | 1988-11-22 | 1992-10-06 | Kao Corporation | Phosphate, liposome comprising the phosphate as membrane constituent, and cosmetic and liposome preparation comprising the liposome |
US5254348A (en) * | 1990-01-26 | 1993-10-19 | Lts Lohmann Therapie Systeme Gmbh & Co. Kg | Transdermal therapeutic system comprising tulobuterol as active substance |
US7033574B1 (en) * | 1990-04-02 | 2006-04-25 | Bracco International B.V. | Stable microbubbles suspensions injectable into living organisms |
US6165500A (en) * | 1990-08-24 | 2000-12-26 | Idea Ag | Preparation for the application of agents in mini-droplets |
US5874479A (en) * | 1991-03-01 | 1999-02-23 | Warner-Lambert Company | Therapeutic permeation enhanced-wound healing compositions and methods for preparing and using same |
US5674912A (en) * | 1991-03-01 | 1997-10-07 | Warner-Lambert Company | Sunscreen-wound healing compositions and methods for preparing and using same |
US5380761A (en) * | 1991-04-15 | 1995-01-10 | Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt. | Transdermal compositions |
US5120561A (en) * | 1991-04-25 | 1992-06-09 | American Lecithin Company | Food composition and method |
US5476651A (en) * | 1991-05-22 | 1995-12-19 | Lvmh Recherche | Cosmetic or pharmaceutical composition, especially dermatological composition, intended for promoting the pigmentation of the skin or hair, containing an extract of cyperus, and the process for its manufacture |
US5550263A (en) * | 1991-06-03 | 1996-08-27 | Karlshamns Lipidteknik Ab | X-ray contrast agent |
US5439967A (en) * | 1991-09-17 | 1995-08-08 | Micro Vesicular Systems, Inc. | Propylene glycol stearate vesicles |
US5206219A (en) * | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
US5814666A (en) * | 1992-04-13 | 1998-09-29 | The United States As Represented By The Department Of Health And Human Services | Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents |
US5484816A (en) * | 1992-07-13 | 1996-01-16 | Shiseido Company, Ltd. | External skin treatment composition |
US5308625A (en) * | 1992-09-02 | 1994-05-03 | Cygnus Therapeutic Systems | Enhancement of transdermal drug delivery using monoalkyl phosphates and other absorption promoters |
US6521250B2 (en) * | 1993-05-06 | 2003-02-18 | Lts Lohmann Therapie-Systeme Gmbh | Transdermal therapeutic system containing estradiol |
US5576016A (en) * | 1993-05-18 | 1996-11-19 | Pharmos Corporation | Solid fat nanoemulsions as drug delivery vehicles |
US5662932A (en) * | 1993-05-18 | 1997-09-02 | Pharmos Corporation | Solid fat nanoemulsions |
US5853755A (en) * | 1993-07-28 | 1998-12-29 | Pharmaderm Laboratories Ltd. | Biphasic multilamellar lipid vesicles |
US5976562A (en) * | 1994-02-01 | 1999-11-02 | Krall; Theodor | Process for producing bactericidal/fungicidal plastic bodies |
US6022561A (en) * | 1994-02-04 | 2000-02-08 | Scotia Lipidteknik Ab | Bilayers preparations |
US5955502A (en) * | 1994-03-30 | 1999-09-21 | Gs Development Ab | Use of fatty acid esters as bioadhesive substances |
US5504117A (en) * | 1994-05-27 | 1996-04-02 | Neptune Pharmaceutical Corporation | Pharmacologic preparation for the treatment of anal disorders |
US5693676A (en) * | 1994-05-27 | 1997-12-02 | Neptune Pharmaceutical Corporation | Nitric oxide donor composition and method for treatment of anal disorders |
US7189761B2 (en) * | 1994-05-27 | 2007-03-13 | Gorfine Stephen R | Nitric oxide donor composition and method for treatment of anal disorders |
US5807573A (en) * | 1994-06-15 | 1998-09-15 | Gs Development Ab | Lipid based composition containing diacylglycerol, phospholipid, polar liquid and biologically active material |
US5985298A (en) * | 1994-10-25 | 1999-11-16 | Revlon Consumer Products Corporation | Cosmetic compositions |
US5858398A (en) * | 1994-11-03 | 1999-01-12 | Isomed Inc. | Microparticular pharmaceutical compositions |
US5726164A (en) * | 1995-03-21 | 1998-03-10 | Novartis Corporation | Nanosuspensions for intravenous administration |
US5879690A (en) * | 1995-09-07 | 1999-03-09 | Perricone; Nicholas V. | Topical administration of catecholamines and related compounds to subcutaneous muscle tissue using percutaneous penetration enhancers |
US6133320A (en) * | 1996-03-19 | 2000-10-17 | Board Of Regents, The University Of Texas System | Treatment of osteoporosis and metabolic bone disorders with nitric oxide substrate and/or donors |
US5869539A (en) * | 1996-04-17 | 1999-02-09 | Board Of Regents, The University Of Texas System | Emulsions of perfluoro compounds as solvents for nitric oxide (NO) |
US6214375B1 (en) * | 1996-07-16 | 2001-04-10 | Generex Pharmaceuticals, Inc. | Phospholipid formulations |
US6045827A (en) * | 1996-11-19 | 2000-04-04 | Meri Charmyne Russell | Treatment of equine laminitis |
US5891472A (en) * | 1996-11-19 | 1999-04-06 | Meri Charmyne Russell | Treatment of equine laminitis |
US6287601B1 (en) * | 1996-11-19 | 2001-09-11 | Meri Charmyne Russell | Topical nitric oxide donor compositions |
US6242099B1 (en) * | 1996-11-21 | 2001-06-05 | Merck S.A. | Microcapsules made of chitin or of chitin derivatives containing a hydrophobic substance, in particular a sunscreen, and process for the preparation of such microcapsules |
US6211250B1 (en) * | 1996-11-22 | 2001-04-03 | Soltec Research Pty Ltd. | Percutaneous delivery system |
US5776494A (en) * | 1996-12-20 | 1998-07-07 | The Procter & Gamble Company | Pharmaceuticals compositions containing gellants in the form of alkyl amides of di-and tri-carboxylic acids |
US6458841B2 (en) * | 1997-09-17 | 2002-10-01 | New England Property Holdings, Llc | Topical and oral delivery of arginine to cause beneficial effects |
US6207713B1 (en) * | 1997-09-17 | 2001-03-27 | Eric T. Fossel | Topical and oral delivery of arginine to cause beneficial effects |
US6464987B1 (en) * | 1998-04-30 | 2002-10-15 | Ucb, S.A. | Pharmaceutical compositions capable of being gelled |
WO1999056725A1 (en) * | 1998-04-30 | 1999-11-11 | Ucb, S.A. | Pharmaceutical compositions capable of being gelled |
US6103275A (en) * | 1998-06-10 | 2000-08-15 | Nitric Oxide Solutions | Systems and methods for topical treatment with nitric oxide |
US6193997B1 (en) * | 1998-09-27 | 2001-02-27 | Generex Pharmaceuticals Inc. | Proteinic drug delivery system using membrane mimetics |
US6936044B2 (en) * | 1998-11-30 | 2005-08-30 | Light Bioscience, Llc | Method and apparatus for the stimulation of hair growth |
US6391869B1 (en) * | 1998-12-14 | 2002-05-21 | Cellergy Pharmaceuticals, Inc. | Compositions and methods for the treatment of anorectal disorders |
US6294192B1 (en) * | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US6191121B1 (en) * | 2000-04-06 | 2001-02-20 | Nicholas V. Perricone | Treatment of skin damage using polyenylphosphatidylcholine |
US6932963B2 (en) * | 2000-06-23 | 2005-08-23 | Nicholas V. Perricone | Treatment of skin wounds using polyenylphosphatidylcholine and alkanolamines |
US7820420B2 (en) * | 2000-08-11 | 2010-10-26 | Whitlock David R | Compositions including ammonia oxidizing bacteria to increase production of nitric oxide and nitric oxide precursors and methods of using same |
US7696247B2 (en) * | 2000-12-21 | 2010-04-13 | Boston Scientific Scimed, Inc. | Lipid-based nitric oxide donors |
US6780849B2 (en) * | 2000-12-21 | 2004-08-24 | Scimed Life Systems, Inc. | Lipid-based nitric oxide donors |
US6555573B2 (en) * | 2000-12-21 | 2003-04-29 | The Quigley Corporation | Method and composition for the topical treatment of diabetic neuropathy |
US20020131994A1 (en) * | 2001-01-10 | 2002-09-19 | Schur Henry B. | Non-irritating formulation for the transdermal delivery of substances |
US20020160040A1 (en) * | 2001-02-20 | 2002-10-31 | Spicer Patrick Thomas | Cubic liquid crystalline compositions and methods for their preparation |
US20020153509A1 (en) * | 2001-02-21 | 2002-10-24 | The Procter & Gamble Company | Functionalized cubic liquid crystalline phase materials and methods for their preparation and use |
US20040096494A1 (en) * | 2001-03-15 | 2004-05-20 | Britta Siekmann | Composition |
US6538061B2 (en) * | 2001-05-16 | 2003-03-25 | General Electric Company | Cosmetic compositions using polyether siloxane copolymer network compositions |
US6568061B2 (en) * | 2001-09-21 | 2003-05-27 | Atlantic Research Corporation | Method for controlling composite preform elements during processing |
US20060275353A1 (en) * | 2002-05-31 | 2006-12-07 | Nicholas V. Perricone | Stable topical drug delivery compositions |
US20100292139A1 (en) * | 2002-05-31 | 2010-11-18 | Perricone Nicholas V | Topical drug delivery using phosphatidylcholine |
US20060105955A1 (en) * | 2002-05-31 | 2006-05-18 | Perricone Nicholas V | Topical drug delivery using phosphatidylcholine |
US20060127469A1 (en) * | 2002-05-31 | 2006-06-15 | Perricone Nicholas V | Methods of delivering stable topical drug compositions |
US8273711B2 (en) * | 2002-05-31 | 2012-09-25 | Transdermal Biotechnology, Inc. | Topical drug delivery using phosphatidylcholine |
US7182956B2 (en) * | 2002-05-31 | 2007-02-27 | Nicholas V. Perricone | Stable topical drug delivery compositions |
US8435942B2 (en) * | 2002-05-31 | 2013-05-07 | Transdermal Biotechnology, Inc. | Methods for formulating stabilized insulin compositions |
US20130331318A1 (en) * | 2002-05-31 | 2013-12-12 | Transdermal Biotechnology, Inc. | Methods of delivering stable topical drug compositions |
US20040197391A1 (en) * | 2002-05-31 | 2004-10-07 | Perricone Nicholas V. | Stable topical drug delivery compositions |
US20130330380A1 (en) * | 2002-05-31 | 2013-12-12 | Transdermal Biotechnology, Inc. | Topical drug delivery using phosphatidylcholine |
US20130331319A1 (en) * | 2002-05-31 | 2013-12-12 | Transdermal Biotechnology, Inc. | Methods of delivering stable topical drug compositions |
US20040191305A1 (en) * | 2002-05-31 | 2004-09-30 | Perricone Nicholas V. | Methods for formulating stabilized insulin compositions |
US20040018237A1 (en) * | 2002-05-31 | 2004-01-29 | Perricone Nicholas V. | Topical drug delivery using phosphatidylcholine |
US20100311696A1 (en) * | 2002-05-31 | 2010-12-09 | Perricone Nicholas V | Topical skin treatment composition |
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 |
US20050226945A1 (en) * | 2004-04-13 | 2005-10-13 | Ruwart Mary J | Compositions and methods for the treatment of radiation burns and other traumatic skin conditions |
US20090324698A1 (en) * | 2004-10-18 | 2009-12-31 | Polymun Scientific Immunbiologische Forschung Gmbh | Liposomal composition comprising an active ingredient for relaxing smooth muscle, the production of this composition and the therapeutic use thereof |
US20090214624A1 (en) * | 2004-11-29 | 2009-08-27 | The University Of Akron | Topical nitric oxide donor devices and methods for their therapeutic use |
US20090304815A1 (en) * | 2006-02-03 | 2009-12-10 | Giulio Cossu | Method of treatment for muscular dystrophy |
US20100048520A1 (en) * | 2006-03-09 | 2010-02-25 | Salix Pharmaceuticals, Ltd. | Rifaximin anti-rectal dysfunction preparation |
US7976743B2 (en) * | 2006-10-16 | 2011-07-12 | Northwestern University | Gas-containing liposomes |
US20110104240A1 (en) * | 2008-06-24 | 2011-05-05 | Micropharma Limited | Nitric Oxide Device and Method for Wound Healing, Treatment of Dermatological Disorders and Microbial Infections |
US20130029989A1 (en) * | 2010-04-15 | 2013-01-31 | The Royal Institution For The Advancement Of Learning/Mcgill University | Topical treatments for pain |
US20120156163A1 (en) * | 2010-12-15 | 2012-06-21 | Susanne Bauman | Methods of decreasing sebum production in the skin |
US20130059017A1 (en) * | 2011-03-17 | 2013-03-07 | Transdermal Biotechinology, Inc. | Topical nitric oxide systems and methods of use thereof |
Non-Patent Citations (8)
Title |
---|
Barenholz (Handbook of Nonmedical Applications of Liposomes 1996, CRC Press page 217). * |
Board Decision filed 5/26/11 in co-pending application 11/506137 * |
Daicheng Liu and Fucui Ma (2011). Soybean Phospholipids, Recent Trends for Enhancing the Diversity and Quality of Soybean Products, Prof. Dora Krezhova (Ed.), ISBN: 978-953-307-533-4, InTech, DOI: 10.5772/20986. Available from: http://www.intechopen.com/books/recent-trends-for-enhancing-the-diversity-and-quality-of-soybean-products/soybean-phosphol * |
Handa (Speaking of: Skin Care 1998; Sterling Publishers; pages 51-52) * |
Hasenhuettl, GL. Food Emulsifiers and their Applications, Chapter 2, pages 11-12, 2008; 2 pages. * |
Phosal 50 PG MSDS 2007 3 pages * |
Robin (A Physiological Handbook for Teachers of Yogasana; 2002, Wheatmark, Inc., pages 283-285) 5 pages * |
Shahidi, F., Nutraceutical and Specialty Lipids and their Co-products 2006, CRC Press, page 515; 1 page. * |
Cited By (92)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9050248B2 (en) | 2002-05-31 | 2015-06-09 | Transdermal Biotechnology, Inc. | Methods of delivering stable topical drug compositions |
US20060275353A1 (en) * | 2002-05-31 | 2006-12-07 | Nicholas V. Perricone | Stable topical drug delivery compositions |
US9060925B2 (en) | 2002-05-31 | 2015-06-23 | Transdermal Biotechnology, Inc. | Methods of delivering stable topical drug compositions |
US8668937B2 (en) | 2011-03-17 | 2014-03-11 | Transdermal Biotechnology, Inc. | Topical nitric oxide systems and methods of use thereof |
US9517179B2 (en) | 2011-03-17 | 2016-12-13 | Transdermal Biotechnology, Inc. | Topical nitric oxide systems and methods of use thereof |
US9937202B2 (en) | 2011-03-17 | 2018-04-10 | Transdermal Biotechnology, Inc. | Topical nitric oxide systems and methods of use thereof |
US9205043B2 (en) | 2012-09-19 | 2015-12-08 | Transdermal Biotechnology, Inc. | Systems and methods for treatment of acne vulgaris and other conditions with a topical nitric oxide delivery system |
US10034898B2 (en) | 2012-09-19 | 2018-07-31 | Transdermal Biotechnology, Inc. | Methods and systems for treatment of inflammatory diseases with nitric oxide |
US8871261B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Cancer treatments and compositions for use thereof |
US8871254B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Systems and methods for treatment of acne vulgaris and other conditions with a topical nitric oxide delivery system |
US8871255B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Treatment of skin and soft tissue infection with nitric oxide |
US8871257B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Prevention and treatment of cardiovascular diseases using systems and methods for transdermal nitric oxide delivery |
US8871260B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Methods and compositions for muscular and neuromuscular diseases |
US9198970B2 (en) | 2012-09-19 | 2015-12-01 | Transdermal Biotechnology, Inc. | Treatment and prevention of learning and memory disorders |
US9198933B2 (en) | 2012-09-19 | 2015-12-01 | Transdermal Biotechnology, Inc. | Cancer treatments and compositions for use thereof |
US9198931B2 (en) | 2012-09-19 | 2015-12-01 | Transdermal Biotechnology, Inc. | Compositions and methods for treatment of osteoporosis and other indications |
US9198930B2 (en) | 2012-09-19 | 2015-12-01 | Transdermal Biotechnology, Inc. | Treatment of skin and soft tissue infection with nitric oxide |
US9198932B2 (en) | 2012-09-19 | 2015-12-01 | Transdermal Biotechnology, Inc. | Techniques and systems for treatment of neuropathic pain and other indications |
US9198854B2 (en) | 2012-09-19 | 2015-12-01 | Transdermal Biotechnology, Inc. | Methods and compositions for muscular and neuromuscular diseases |
US9198853B2 (en) | 2012-09-19 | 2015-12-01 | Transdermal Biotechnology, Inc. | Methods and systems for treatment of inflammatory diseases with nitric oxide |
US9480708B2 (en) | 2012-09-19 | 2016-11-01 | Transdermal Biotechnology, Inc. | Treatment and prevention of learning and memory disorders |
US10034897B2 (en) | 2012-09-19 | 2018-07-31 | Transdermal Biotechnology, Inc. | Methods and compositions for muscular and neuromuscular diseases |
US10034896B2 (en) | 2012-09-19 | 2018-07-31 | Transdermal Biotechnology, Inc. | Compositions and methods for treatment of osteoporosis and other indications |
US8871262B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Compositions and methods for treatment of osteoporosis and other indications |
US9295638B2 (en) | 2012-09-19 | 2016-03-29 | Transdermal Biotechnology, Inc. | Prevention and treatment of cardiovascular diseases using systems and methods for transdermal nitric oxide delivery |
US9968635B2 (en) | 2012-09-19 | 2018-05-15 | Transdermal Biotechnology, Inc. | Treatment of skin and soft tissue infection with nitric oxide |
US9968634B2 (en) | 2012-09-19 | 2018-05-15 | Transdermal Biotechnology, Inc. | Techniques and systems for treatment of neuropathic pain and other indications |
US9950004B2 (en) | 2012-09-19 | 2018-04-24 | Transdermal Biotechnology, Inc. | Treatment and prevention of learning and memory disorders |
US8871258B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Treatment and prevention of learning and memory disorders |
US9844565B2 (en) | 2012-09-19 | 2017-12-19 | Transdermal Biotechnology, Inc. | Systems and methods for treatment of acne vulgaris and other conditions with a topical nitric oxide delivery system |
US9827266B2 (en) | 2012-09-19 | 2017-11-28 | Transdermal Biotechnology, Inc. | Prevention and treatment of cardiovascular diseases using systems and methods for transdermal nitric oxide delivery |
US9795632B2 (en) | 2012-09-19 | 2017-10-24 | Transdermal Biotechnology, Inc. | Cancer treatments and compositions for use thereof |
US8871259B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Techniques and systems for treatment of neuropathic pain and other indications |
US8871256B2 (en) | 2012-09-19 | 2014-10-28 | Transdermal Biotechnology, Inc. | Methods and systems for treatment of inflammatory diseases with nitric oxide |
US9480709B2 (en) | 2012-09-19 | 2016-11-01 | Transdermal Biotechnology, Inc. | Methods and compositions for muscular and neuromuscular diseases |
US9480706B2 (en) | 2012-09-19 | 2016-11-01 | Transdermal Biotechnology, Inc. | Systems and methods for treatment of acne vulgaris and other conditions with a topical nitric oxide delivery system |
US9480711B2 (en) | 2012-09-19 | 2016-11-01 | Transdermal Biotechnology, Inc. | Techniques and systems for treatment of neuropathic pain and other indications |
US9480707B2 (en) | 2012-09-19 | 2016-11-01 | Transdermal Biotechnology, Inc. | Methods and systems for treatment of inflammatory diseases with nitric oxide |
US9480710B2 (en) | 2012-09-19 | 2016-11-01 | Transdermal Biotechnology, Inc. | Compositions and methods for treatment of osteoporosis and other indications |
US9480705B2 (en) | 2012-09-19 | 2016-11-01 | Transdermal Biotechnology, Inc. | Treatment of skin and soft tissue infection with nitric oxide |
US9498535B2 (en) | 2013-03-13 | 2016-11-22 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US9844506B2 (en) | 2013-03-13 | 2017-12-19 | Transdermal Biotechnology, Inc. | Compositions and methods for affecting mood states |
US9393265B2 (en) | 2013-03-13 | 2016-07-19 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US9480642B2 (en) | 2013-03-13 | 2016-11-01 | Transdermal Biotechnology, Inc. | Compositions and methods for affecting mood states |
US9393264B2 (en) | 2013-03-13 | 2016-07-19 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
US9387159B2 (en) | 2013-03-13 | 2016-07-12 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9339457B2 (en) | 2013-03-13 | 2016-05-17 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US9585817B2 (en) | 2013-03-13 | 2017-03-07 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9585931B2 (en) | 2013-03-13 | 2017-03-07 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US9585829B2 (en) | 2013-03-13 | 2017-03-07 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9597401B2 (en) | 2013-03-13 | 2017-03-21 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US9597400B2 (en) | 2013-03-13 | 2017-03-21 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9636291B2 (en) | 2013-03-13 | 2017-05-02 | Transdermal Biotechnology, Inc. | Hair treatment systems and methods using peptides and other compositions |
US9682102B2 (en) | 2013-03-13 | 2017-06-20 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US9687504B2 (en) | 2013-03-13 | 2017-06-27 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
US9687520B2 (en) | 2013-03-13 | 2017-06-27 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
US9694083B2 (en) | 2013-03-13 | 2017-07-04 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
US9694029B2 (en) | 2013-03-13 | 2017-07-04 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
US9700626B2 (en) | 2013-03-13 | 2017-07-11 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US9717680B2 (en) | 2013-03-13 | 2017-08-01 | Transdermal Biotechnology, Inc. | Topical systems and methods for treating sexual dysfunction |
US9724419B2 (en) | 2013-03-13 | 2017-08-08 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9757467B2 (en) | 2013-03-13 | 2017-09-12 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US9320758B2 (en) | 2013-03-13 | 2016-04-26 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
US9827316B2 (en) | 2013-03-13 | 2017-11-28 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US9320706B2 (en) | 2013-03-13 | 2016-04-26 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
US9439926B2 (en) | 2013-03-13 | 2016-09-13 | Transdermal Biotechnology, Inc. | Topical systems and methods for treating sexual dysfunction |
US9314423B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Hair treatment systems and methods using peptides and other compositions |
US9849160B2 (en) | 2013-03-13 | 2017-12-26 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
US9872818B2 (en) | 2013-03-13 | 2018-01-23 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9913793B2 (en) | 2013-03-13 | 2018-03-13 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9931370B2 (en) | 2013-03-13 | 2018-04-03 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9937221B2 (en) | 2013-03-13 | 2018-04-10 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US9314417B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Treatment of skin, including aging skin, to improve appearance |
US9943562B2 (en) | 2013-03-13 | 2018-04-17 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US9314433B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
US9956290B2 (en) | 2013-03-13 | 2018-05-01 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9314422B2 (en) | 2013-03-13 | 2016-04-19 | Transdermal Biotechnology, Inc. | Peptide systems and methods for metabolic conditions |
US9295647B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US10028994B2 (en) | 2013-03-13 | 2018-07-24 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
US9295637B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Compositions and methods for affecting mood states |
US10034944B2 (en) | 2013-03-13 | 2018-07-31 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US10034914B2 (en) | 2013-03-13 | 2018-07-31 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
US10034828B2 (en) | 2013-03-13 | 2018-07-31 | Transdermal Biotechnology, Inc. | Hair treatment systems and methods using peptides and other compositions |
US9295636B2 (en) | 2013-03-13 | 2016-03-29 | Transdermal Biotechnology, Inc. | Wound healing using topical systems and methods |
US9241899B2 (en) | 2013-03-13 | 2016-01-26 | Transdermal Biotechnology, Inc. | Topical systems and methods for treating sexual dysfunction |
US10064955B2 (en) | 2013-03-13 | 2018-09-04 | Transdermal Biotechnology, Inc. | Cardiovascular disease treatment and prevention |
US10071117B2 (en) | 2013-03-13 | 2018-09-11 | Transdermal Biotechnology, Inc. | Immune modulation using peptides and other compositions |
US10080768B2 (en) | 2013-03-13 | 2018-09-25 | Transdermal Biotechnology, Inc. | Systems and methods for delivery of peptides |
US10155048B2 (en) | 2013-03-13 | 2018-12-18 | Transdermal Biotechnology, Inc. | Methods and systems for treating or preventing cancer |
US10188603B2 (en) | 2013-03-13 | 2019-01-29 | Transdermal Biotechnology, Inc. | Topical systems and methods for treating sexual dysfunction |
US10213457B2 (en) | 2013-03-13 | 2019-02-26 | Transdermal Biotechnology, Inc. | Brain and neural treatments comprising peptides and other compositions |
US10226511B2 (en) | 2013-03-13 | 2019-03-12 | Transdermal Biotechnology, Inc. | Memory or learning improvement using peptide and other compositions |
Also Published As
Publication number | Publication date |
---|---|
US20060275353A1 (en) | 2006-12-07 |
AU2003231943A1 (en) | 2003-12-19 |
US20040197391A1 (en) | 2004-10-07 |
JP2005531595A (en) | 2005-10-20 |
AU2003231943B2 (en) | 2006-03-16 |
US20130330380A1 (en) | 2013-12-12 |
US20060105955A1 (en) | 2006-05-18 |
US20060127469A1 (en) | 2006-06-15 |
EP1509243A1 (en) | 2005-03-02 |
US20100292139A1 (en) | 2010-11-18 |
CN1671409A (en) | 2005-09-21 |
IL165480A0 (en) | 2006-01-15 |
US20040018237A1 (en) | 2004-01-29 |
CA2487305A1 (en) | 2003-12-11 |
CN100509054C (en) | 2009-07-08 |
US20150238608A1 (en) | 2015-08-27 |
US7182956B2 (en) | 2007-02-27 |
US8273711B2 (en) | 2012-09-25 |
HK1083009A1 (en) | 2006-06-23 |
EP1509243A4 (en) | 2009-06-24 |
IL165480A (en) | 2012-10-31 |
US20130331318A1 (en) | 2013-12-12 |
US9050248B2 (en) | 2015-06-09 |
US20130330381A1 (en) | 2013-12-12 |
US20110130330A1 (en) | 2011-06-02 |
EP1509243B1 (en) | 2017-03-22 |
US20130331319A1 (en) | 2013-12-12 |
US9060925B2 (en) | 2015-06-23 |
ES2632912T3 (en) | 2017-09-18 |
WO2003101480A1 (en) | 2003-12-11 |
US20150004196A1 (en) | 2015-01-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9050248B2 (en) | Methods of delivering stable topical drug compositions | |
CA2511849C (en) | Stable topical drug delivery compositions comprising a multilamellar liquid crystal phosphatidylcholine carrier | |
US8435942B2 (en) | Methods for formulating stabilized insulin compositions | |
US20100311696A1 (en) | Topical skin treatment composition | |
US20020131994A1 (en) | Non-irritating formulation for the transdermal delivery of substances | |
JP2001522804A (en) | Penetration enhancement and stimulation reduction system | |
EP1522316B1 (en) | Transdermal absorption preparation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: TRANSDERMAL BIOTECHNOLOGY, INC., CONNECTICUT Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PERRICONE, NICHOLAS V.;REEL/FRAME:030845/0498 Effective date: 20070327 Owner name: PERRICONE, NICHOLAS V., CONNECTICUT Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:POTINI, CHIM;REEL/FRAME:030845/0448 Effective date: 20040106 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |