WO1995011017A1 - Ibuprofen and flurbiprofen as anti-pruritic agents - Google Patents
Ibuprofen and flurbiprofen as anti-pruritic agents Download PDFInfo
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- WO1995011017A1 WO1995011017A1 PCT/EP1994/003442 EP9403442W WO9511017A1 WO 1995011017 A1 WO1995011017 A1 WO 1995011017A1 EP 9403442 W EP9403442 W EP 9403442W WO 9511017 A1 WO9511017 A1 WO 9511017A1
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- ibuprofen
- flurbiprofen
- composition
- pruritus
- salts
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
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- 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
Definitions
- the present invention relates to use of ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts for treating pruritus in animals including human beings, the ibuprofen, flurbiprofen and/or pharmaceutically acceptable salt or salts being administered topically; use of ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts in the preparation of a medicament for treating pruritus topically; and pharmaceutical compositions comprising ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts as anti- pruritic agent or agents, the compositions having anti- pruritic activity.
- the compositions are suitable for treatment of itching animal, preferably human, skin when applied topically thereto.
- Pruritus or itching, is an unpleasant condition of the skin surface. Although pruritus is a complex phenomena, it may be defined crudely as the skin sensation which evokes the motor response of scratching. The causes of pruritus are due to many different conditions . Some causes are local and can easily be removed, for example slight mechanical irritation such as contact with rough, woollen underclothing, or parasites such as lice or scabies. Some causes of pruritus are more general and can result in a condition which is chronic.
- Ibuprofen the chemical name of which is 2-(4- isobutylphenyDpropionic acid and flurbiprofen, the chemical name of which is 2- (2-fluoro-4-biphenylyl) - propionic acid
- Ibuprofen and flurbiprofen are known to have anti-inflammatory, antipyretic and analgesic activity.
- Known uses of ibuprofen and flurbiprofen include the treatment of pain and inflammation in musculoskeletal disorders such as rheumatic disease, and the treatment of pain in a variety of other disorders, for example headache, neuralgia and dysmenorrhoea.
- Ibuprofen and flurbiprofen have been ingredients in many different topical compositions, for treatment of the indications described above.
- Patent Biopharmaceutics Inc discloses a composition for treating the symptoms of haemorrhoids and other anorectal diseases (which includes, inter alia, pruritus) using hyaluronic acid as the sole anti- pruritic ingredient.
- a disclosure that any, unspecified anti-inflammatory agent might be added as an additional optional ingredient to this composition does not suggest that the anti-inflammatory agent would have any other activity, or would be added for any other purpose than optionally to add anti-inflammatory properties to the anti-pruritic composition.
- At least fifty papers in the medical literature disclose anedoctal evidence that systemically (usually orally) administered ibuprofen may be associated with pruritic symptoms for a small minority of patients. This is evidenced by, for example, the review paper 'Cutaneous Reactions to Rheumatological Drugs' (Clin. Rheum. Dis., 1982, 8(2), 493-516, Bailin P.L. et al) in which pruritus is stated to be 'a commonly mentioned' cutaneous adverse reaction after ingestion of ibuprofen.
- the minor pruritic effects associated with the above topical compositions may not be associated with ibuprofen, but could arise from other factors or ingredients, for example, the pH of the composition, the excipients and/or the ibuprofen ester (ibuprofen piconol) .
- NSAID non-steroidal antiinflammatory agents
- ibuprofen non-steroidal antiinflammatory agents
- UV-B radiation ultraviolet-B radiation
- UV-B radiation is defined herein as electromagnetic radiation having a wavelength in the inclusive range from 280 n to 320 nm.
- ibuprofen, flurbiprofen and/or one or more of their pharmaceutical acceptable salt or salts are useful as anti-pruritic agent or agents in the topical treatment and alleviation of the symptoms of pruritus.
- the anti-pruritic agent or agents comprise other than solely ibuprofen (for example flurbiprofen or flurbiprofen and ibuprofen together) .
- the present invention provides for use of ibuprofen flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts for the topical treatment of pruritus in animals, preferably human beings.
- ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts are administered topically to animals, preferably human beings, suffering from pruritus, the ibuprofen, flurbiprofen and/or their pharmaceutically acceptable salt or salts being applied to the affected area to achieve an anti-pruritic response and being present in an anti-pruritically effective amount.
- the anti-pruritic agent or agents comprise other than solely ibuprofen.
- ibuprofen and flurbiprofen contain a single chiral centre at an asymmetrically substituted carbon atom, and therefore both exist in enantiomeric forms.
- Racemic ibuprofen consists of a 50:50 mixture of (+)2-
- racemic flurbiprofen includes the racemic mixture, the (+) and (-) enantiomers separately and any mixtures thereof sufficient to give an anti- pruritic response.
- racemic flurbiprofen consists of a 50:50 mixture of (+) 2-(2-fluoro-4- biphenylyDpropionic acid and (-) 2-(2-fluoro-4- biphenylyDpropionic acid.
- flurbiprofen as used herein includes the racemic mixture, the (+) and (-) enantiomers separately and any mixtures thereof sufficient to give an anti- pruritic response.
- Ibuprofen and/or flurbiprofen may form salts with organic or inorganic bases.
- the terms ibuprofen and/or flurbiprofen salt and/or salts as used herein include all such salts of these compounds which are pharmaceutically acceptable (i.e. non-toxic at therapeutically effective doses) and are present in amounts sufficient to give an anti-pruritic response.
- Particularly suitable salts of ibuprofen and/or flurbiprofen comprise alkali metal salts (for example sodium and/or potassium salts) , alkaline earth metal salts (for example magnesium and/or calcium salts) , aluminium salts, ammonium salts, salts of suitable organic bases (for example salts of alkylamines and/or N-methyl-D-glutamine) , salts of amino acids (for example salts of arginine and/or lysine) .
- alkali metal salts for example sodium and/or potassium salts
- alkaline earth metal salts for example magnesium and/or calcium salts
- aluminium salts for example magnesium and/or calcium salts
- ammonium salts salts of suitable organic bases
- salts of amino acids for example salts of arginine and/or lysine
- a preferred salt of ibuprofen is sodium ibuprofen, more preferably S(-)sodium ibuprofen. It will be readily understood that these salts may also exist as racemates, separate enantiomers and/or mixtures thereof and the terms ibuprofen and/or flurbiprofen salt and/or salts as used herein include racemates, separate enantiomers or any mixtures thereof of all pharmaceutically acceptable ibuprofen and/or flurbiprofen salt or salts present in an amount sufficient to give an anti-pruritic response. It will be appreciated that such salts, provided they are pharmaceutically acceptable, may be used in therapy in place of ibuprofen and/or flurbiprofen.
- Such salts are prepared from ibuprofen and/or flurbiprofen with a suitable base in a conventional manner.
- Ibuprofen, flurbiprofen and/or their salt or salts may exist in more than one crystal form and references to these compounds herein include each crystal form and mixtures thereof sufficient to give an anti-pruritic response.
- Ibuprofen, flurbiprofen and/or their salt or salts may also exist in the form of solvates, for example hydrates, and references to these compounds herein include each solvate and mixtures thereof present in an amount sufficient to give an anti-pruritic response.
- ibuprofen, flurbiprofen and/or their pharmaceutically acceptable salts has been demonstrated by means of tests on animals, including human beings, such as those described hereinafter in the Examples.
- both ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts are useful in the treatment of pruritus in animals, preferably human beings.
- the anti-pruritic agent or agents comprise other than solely ibuprofen.
- ibuprofen, flurbiprofen and/or their pharmaceutically acceptable salt or salts are administered topically, more preferably to itching animal skin, most preferably itching human skin.
- a suitable daily dose of ibuprofen, flurbiprofen and/or their pharmaceutically acceptable salt or salts for administration to animals, preferably human beings, to treat pruritus may be generally from about lmg to about 10,000mg, more usually from about 5mg to about 5000mg, most usually from about lOmg to about lOOOmg, given in a single dose or in divided doses at one time
- pruritic symptoms may occur on normal and abnormal skins and may be caused by a number of metabolic pathways (reference is made to R Winkelmann, Medical Clinics of North America, Vol 66, No 5, September 1982) .
- Some pruritic conditions may arise from one or both of the following non-prostaglandins mechanisms, namely via histamine and serotonin production.
- causes of pruritus include one or more of any of the following: induction by UV-radiation (for example sunburn) ; external non-UV stimuli (for example contact with fibres [such as wool and/or synthetic fibres] , aqueous contact [aquagenic pruritus] and/or cholinergic pruritus [related to heat and/or exercise] ) ; enteral and/or parenteral contact with histamine- producing substances (for example food substances and/or plants) ; administration of drugs (for example opiates, barbiturates and/or salicylamilides) ; toxic products (for example bile salts and/or urea) released due to failure of body organs (for example kidney and/or liver failure) ; pruriginous disease (for example leprosy) ; stimulation of (or other changes in) nerve endings, fibres and/or receptors in the skin; psychogenic causes; and xerosis (abnormal dryness) of the skin in the elderly.
- Pruritus, or itching may be classified amongst the following conditions (see Winkelmann 1982) :
- Physiologic itch is a short-lived cutaneous response to the usual environmental and body stimuli which may or may not elicit scratching, and is to be distinguished form tickle which is considered to be moving touch plus its affective response.
- Pathologic itch is an intense cutaneous discomfort occurring with pathologic change in the skin or body which usually elicits vigorous scratching or other effort at relief.
- Spontaneous itch is itching unrelated to pathologic change in the skin or cutaneous nerves and elicited by toxic or metabolic change within the body. This may be physiologic or pathologic itch.
- Focal itch is a locus of pathologic itching caused by cutaneous nerve or other tissue change.
- Scattered itch is multiple, distant areas of pruritus and may exist in the skin following an itching excitation in only one skin area.
- Referred itch is a more recent name for scattered itch but often in the same dermatome.
- Conversion itch is a condition described in 1964 by Winkelmann to account for the change of a usual sensory experience into itch, as touch or tickle to itch in atopic skin of normal appearance.
- Itchy skin is an area of hyperresponsiveness to stimuli for itch about a primary stimulus zone for itch or a primary skin inflammation. This is analogous to the hyperalgesic zone about a skin spot stimulated to pain.
- Central neural itch is itching stimulated and/or maintained by the central nervous system. Cutaneous changes are not primary.
- Dermatitis or eczema
- Dermatitis is a superficial inflammation of the skin, and is characterised by vesicles (when acute) , redness, oedema, oozing, crusting, scaling and usually itching.
- Contact dermatitis is an acute or chronic inflammation of the skin which is often sharply demarcated. It is produced by contact between the skin and some substance or stimulus to which the skin is sensitive, for example those described above.
- Atopic dermatitis is a chronic, itching superficial inflammation of the skin usually occurring in individuals with a personal family history of allergic disorders (for example hay fever, asthma) due to an inherited state of hypersensitivity. It is also known as infantile eczema as it often starts in infants at about the age of 3 to 4 months.
- Seborrhoeic dermatitis is an inflammatory scaling disease of the scalp, face and occasionally other areas of the body which produces variable amounts of itching.
- Nummular dermatitis is a chronic dermatitis characterised by inflamed, coin-shaped, vesicular, crusted, scaly and usually pruritic lesions.
- Pompholyx is a chronic condition characterised by deep- seated itchy vesicles on the palms, sides of the fingers and soles of the feet. When it occurs on the fingers and hands it is known as cheiropompholyx. On the toes and feet it is known as podopompholyx.
- Generalised exfoliative dermatitis is a severe widespread erythema and scaling of the skin. Itching may be severe or absent.
- Localised scratch dermatitis is a chronic, superficial, pruritic inflammation of the skin.
- Impetigo is a superficial, vesiculopustular skin infection seen chiefly in children. It is usually caused by the staphylococcus aureus. Itching is common and scratching may spread the infection, as the discharge from the vesicles is infectious.
- Ecthyma is an ulcerative form of impetigo.
- Scabies is a transmissible, parasitic skin infection caused by the mite Sarcoptes Scabies.
- the condition is characterised by superficial burrows, intense pruritus and secondary skin infection. The intense itching of this condition gives scabies its popular name of 'itch'.
- Pediculosis is infestation by lice.
- Urticaria (otherwise known as hives or nettle rash) results in local wheals and erythema in the dermis.
- Food allergy is a common cause of urticaria, which is generally agreed to be an allergic reaction on behalf of the sufferer to some substance to which they are hypersensitive.
- Pruritus is generally the first symptom, occurring shortly after exposure to the substance which causes the condition.
- Lichen simplex and lichen planus are recurrent, pruritic, inflammatory eruptions characterised by small, discrete, angular papules that coalesce into rough scaly patches with consequent thickening and hardening of the skin.
- Miliaria (prickly heat) is an acute, inflammatory, pruritic eruption due to retained extravasated sweat, often affecting people travelling to the tropics. A similar condition can occur in some people upon getting warm in bed or at the start of spring or autumn when changes in the size of blood vessels in the skin take place.
- Dermatitis herpetiformis is a chronic eruption characterised by clusters of intensely pruritic vesicles, papules and urticaria-like lesions.
- pruritus ani A very aggravated form of itching may occur at the anus, known as pruritus ani. This is often caused by threadworms.
- pruritus vulvae An equally troublesome form of itching known as pruritus vulvae can occur around the vagina and may be associated with excessive vaginal discharge.
- Pruritus in the elderly may be due to a primary skin disease, a systemic disease or may have multifactorial or idiopathic causes. It is believed that xerosis is the most common cause of itching in the elderly.
- pruritus Other more systemic conditions that may give rise to pruritus comprise obstructive biliary disease, uraemia, lymphomas, leukaemias, polycythemia rubra vera, and diabetes mellitus. Jaundice and glomerulo-nephritis may also be accompanied by itchiness in a milder degree.
- Animals that may be treated by the methods of the present invention and/or with the compositions of the present invention comprise human beings as well as non-human animals and the term 'animal' as used herein should be construed as including human beings.
- Non-human animals that may be so treated comprise those commonly encountered as domestic pets (for example cats, dogs, rabbits and/or guinea pigs); those used commercially (for example livestock [such as pigs, cows and/or sheep] and/or working animals [such as horses] ) and/or those animals kept in zoos or wildlife parks for example zebra, lions and/or elephants) .
- the present invention should not be considered limited to those animals mentioned above and could in principle be used for the treatment of any animals including non-mammals (for example reptiles and/or birds) .
- Aquatic animals for example fish and/or aquatic mammals
- Methods and/or compositions of the present invention may be particularly useful in preventing non- known animals from scratching their itching skin or hide. Scratching may be therapeutically undesirable as it may cause damage or aggravate any underlying condition, and/or may be cosmetically undesirable as it may blemish the skin or hide. Inhibition of scratching may be particularly important (either as a method of therapy or as a non-therapeutic cosmetic treatment) for animals with a high cultural and/or economic value (for example endangered species bred in captivity for possible re-introduction into the wild [such as pandas] , highly prized animals [such as racehorses] and/or animals bred for their skin to produce leather or fur [such as mink] ) .
- Scratching may be therapeutically undesirable as it may cause damage or aggravate any underlying condition, and/or may be cosmetically undesirable as it may blemish the skin or hide. Inhibition of scratching may be particularly important (either as a method of therapy or as a non-therapeutic cosmetic
- the animal treated by the methods of, or with the compositions of, the present invention is a mammal, more preferably a human being.
- a further aspect of present invention also provides a pharmaceutical composition
- a pharmaceutical composition comprising ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts as anti- pruritic agent or agents, the composition having anti ⁇ pruritic activity.
- the ibuprofen, flurbiprofen and/or their pharmaceutically acceptable salt or salts are the only anti-pruritic agent or agents.
- the composition is in a form suitable for topical application, preferably in a form suitable for application to itching animal, preferably human, skin.
- a still further aspect of the present invention also provides for use of ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts in the preparation of a topical medicament for treating pruritus.
- the present invention further provides a method of treating pruritus on animals, including human beings, using the compositions described herein.
- ibuprofen is the sole anti-pruritic agent the pruritus treated according to this method has been induced by other than UV-B radiation.
- a topical medicament of the present invention may alleviate pruritic symptoms with or without a therapeutical effect on any underlying condition.
- the present invention further provides a non-therapeutic method of cosmetic treatment for inhibiting in animals, including human beings the urge to scratch the skin elicited by itching, comprising applying topically to the animal a composition comprising ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts.
- the cosmetic treatment of the present invention acts to reduce the degree of scratching by an animal by an amount sufficient to result in a corresponding reduction and/or elimination of the cosmetically undesirable effects caused by such scratching.
- Compositions suitable for use in such a topical treatment may comprises those compositions known to persons skilled in the art of cosmetics formulation and/or the pharmaceutical compositions described herein.
- the method of therapy, treatment (including cosmetic treatment) , use and/or compositions described herein may be applied in conjunction with any other compatible therapy, treatment (including cosmetic treatment) and/or composition also for the treatment (including cosmetic treatment) of pruritus, and/or the treatment of any other condition (for example any condition which may be the underlying cause of the pruritic symptoms) .
- the amount of the ibuprofen, flurbiprofen and/or their pharmaceutically acceptable salt or salts in the topical formulation should be such that an anti- pruritically effective amount of this compound or these compounds is delivered during the period of time for which the topical formulation is intended to be on the skin.
- the formulation should remain on the skin for at least that period of time necessary to produce an effective anti-pruritic response in the area of skin treated.
- the delay before onset of any anti-pruritic effect depends on many factors including the nature of the pruritus, the area and type of skin being treated and the species and age of patient, as well as the nature of the formulation. Typically for an adult human patient, the delay before onset of an anti-pruritic effect may be from about a few seconds to about an hour or more, more usually from about one to twenty minutes.
- topical compositions of the present invention comprise ibuprofen, flurbiprofen and/or one or more of their pharmaceutically acceptable salt or salts in an amount from about 1% to about 25% by weight, more preferably from about 2% to about 15% by weight, most preferably from about 2.5% to about 10% by weight of the composition.
- Formulations used in methods of, or as compositions of, the present invention may provide a local and/or systemic therapeutic and/or cosmetic effect, and may be administered in a prophylactic manner, for example to prevent the onset of pruritus and/or to prevent the urge to scratch the skin.
- Such formulations, or compositions may be formulated in a manner known to those skilled in the art to give a controlled release, for example rapid release or sustained release, of , ibuprofen, flurbiprofen and/or their pharmaceutically acceptable salt or salts.
- the ibuprofen and/or flurbiprofen ingredient may be replaced or supplemented by any pharmaceutically acceptable salt or salts of ibuprofen and/or flurbiprofen compatible with the ingredients used in the formulation.
- Suitable topical compositions of the present invention may comprise a matrix in which the ibuprofen and/or flurbiprofen, are dispersed so that the compound or compounds are held in contact with the skin in order to administer the compound or compounds transdermally.
- Suitable matrices for topical application may comprise topical delivery devices such as cataplasms, poultices, patches or impregnated bandages.
- a composition suitable for transdermal delivery may be prepared by mixing the ibuprofen and/or flurbiprofen with a topical vehicle (for example a mineral oil, petrolatum, light liquid paraffin and/or a wax [such as paraffin wax and/or beeswax] ) together with a potential transdermal accelerant such as dimethyl sulphoxide and/or propylene glycol.
- a topical vehicle for example a mineral oil, petrolatum, light liquid paraffin and/or a wax [such as paraffin wax and/or beeswax]
- a potential transdermal accelerant such as dimethyl sulphoxide and/or propylene glycol.
- the ibuprofen and/or flurbiprofen may be mixed with and/or dispersed in, a pharmaceutically acceptable foam, paste, salve, lotion, cream, ointment, emulsion and/or gel base, and/or applied in the form of a spray.
- a suitable cream may be prepared by incorporating the ibuprofen and/or flurbiprofen in petrolatum and/or light liquid paraffin, dispersed in an aqueous medium using a surfactant.
- a suitable ointment may be prepared by mixing the ibuprofen and/or flurbiprofen with a mineral oil, petrolatum and/or a wax (for example paraffin wax and/or beeswax) .
- a suitable gel may be prepared by mixing the ibuprofen and/or flurbiprofen with a topical vehicle comprising a gelling agent (for example basified Carbomer BP) in the presence of water.
- a gelling agent for example basified Carbomer BP
- compositions of the present invention comprise a pharmaceutically acceptable diluent or carrier, more preferably an aqueous solvent, most preferably purified water.
- compositions of the present invention also comprise a thickening agent in an amount from about 0.1% to about 10% by weight, more preferably from about 0.2% to about 5% by weight, most preferably from about 0.5% to about 3% by weight of the composition.
- the thickening agent may comprise hydroxyethyl cellulose, and/or a carboxyvinyl cross polymer (for example that available commercially from B.F. Goodrich Limited under the trade name Carbopol 980NF) .
- compositions of the present invention further comprise a pH adjusting agent, more preferably a basic pH adjusting agent.
- the pH adjusting agent is present in an amount which is sufficient to activate the thickening agent, if present, and which will keep the pH of the composition within a pharmaceutically and cosmetically acceptable range that will not damage the skin. More preferably the pH of the composition is from about 5.0 to about 9.0.
- the pH adjusting agent is preferably present in an amount from a trace amount to about 15% by weight, more preferably from about 0.01% to about 12% by weight, most preferably from about 0.1% to about 10% by weight of the composition.
- T h e p H adjusting agent may comprise sodium citrate, sodium hydroxide, potassium hydroxide and/or N,N,N',N'- tetrakis (2-hydroxypropyl) ethylenediamine (available commercially under the trade name Quadrol) .
- compositions of the present invention may additionally comprise a preservative.
- the preservative is present in an amount from a trace amount to about 5% by weight, more preferably from about 0.1% to about 3% by weight, most preferably from about 0.5% to about 2% by weight of the composition.
- the preservative may comprise bronopol, sodium dehydroacetate , polyhexamethy1enebiguanide hydrochloride, isothiazolone diazolidinylurea and/or 2- phenoxyethanol (available commercially under the trade name Phenoxetol Nipa) .
- compositions of the present invention may further comprise a humectant to improve the feel of the composition on the skin.
- humectant is present in an amount from about 1% to about 30% by weight, more preferably from about 5 to about 20% by weight, most preferably from about 7% to about 15% by weight of the composition.
- the humectant may comprise a glycol which is defined herein as one or more organic compounds each having at least two hydroxy groups preferably on adjacent atoms. More preferably the glycol may comprise polyethylene glycol, glycerin and/or any mixture of these.
- a composition of the present invention is a gel.
- a gel may be a clear gel comprising a clarifying agent, preferably a denaturated alcohol, more preferably denaturated ethanol.
- the clarifying agent is present in an amount from about 5% to about 60% by weight of the composition.
- a composition of the present invention is an emulsion, such an emulsion may be either an oil-in-water or a water-in-oil emulsion.
- the oil phase of an emulsion that may comprise a composition of the present invention may comprise one or more of the following ingredients and/or any mixture of these: hydrocarbon oils (for example paraffin and/or mineral oils) ; waxes (for example beeswax and/or paraffin wax; natural oils (for example sunflower oil, apricot kernel oil, shea butter and/or jojoba oil) ; silicone oils (for example dimethicone, cyclomethicone and/or cetyldimethicone) ; fatty acid esters (for example isopropyl palmitate and/or isopropyl myristate) ; and fatty alcohols (for example cetyl alcohol and/or stearyl alcohol) ;
- hydrocarbon oils for example paraffin and/or mineral oils
- waxes for example beeswax and/or paraffin wax
- natural oils for example sunflower oil, apricot kernel oil, shea butter and/or jojoba oil
- silicone oils for example dimethicon
- the oil phase comprises from about 5% to about 30% by weight, more preferably from about 10% to about 20% by weight of the composition.
- Emulsifiers that may be used in a composition of the present invention may be any emulsifiers known in the art for use in water-in-oil or oil-in-water emulsions.
- Those compositions of the present invention that are emulsions can be prepared by using an emulsifier and/or a mixture of emulsifiers selected from known emulsifiers acceptable for use in topical compositions which may comprise one or more of the following ingredients and/or any mixtures of these.
- sesquioleates for example sorbitan sesquioleates [such as that available commercially from ICI under the trade name Arlacel 83]); ethoxylated esters of derivatives of natural oils (for example polyethoxylated esters of hydrogenated castor oils [such as that available commercially from ICI under the' trade name Arlacel 989]); silicone emulsifiers (for example silicone polyols [such as those available commercially from Th.
- the amount of emulsifier optionally present in a water-in-oil emulsion that may comprise a composition of the present invention is preferably in the range from about 0.1% to about 20% by weight of the composition.
- the amount of emulsifier optionally present in an oil-in-water emulsion that may comprise a composition of the present invention is preferably in the range from about 0.1% to about 20% by weight of the composition.
- composition of the present invention is other than an emulsion, an emulsifying ingredient and/or surfactant (for example one of those emulsifiers listed above) , may still be present (for example in the amounts given above) as a surface active agent to promote greater therapeutic activity in the composition when it is applied topically.
- an emulsifying ingredient and/or surfactant for example one of those emulsifiers listed above
- surfactant for example one of those emulsifiers listed above
- compositions of the present invention may additionally comprise one or more other component, components and/or any mixture of these, which will be well known to those skilled in the art and may be selected from: emulsion stabilisers (for example stearyl alcohols and/or cetyl alcohols) and/or emulsion stabilising salts
- sequestrants for example tetra sodium ethylene diamine tetra acetate dihydrates [such as that available commercially from Rhone Poulenc under the tradename Sequestene NA4] ) , preferably in an amount from a trace amount to about 1% by weight of that composition
- anti-oxidants for example DL ⁇ tocopherol acetate and/or butylated hydroxytoulene
- emollients for example mineral oil, polymethylsiloxane, sweet almond oil, petroleum jelly, isopropyl myristate and/or triglycerides of fatty acids [such as lauric triglyceride, capric/caprylic triglyceride, and/or mixed triglycerides ⁇ eg that available commercially from Huls UK Ltd under the trade name Miglyol 810 ⁇ ]
- fatty acids such as lauric triglyceride, capric/caprylic triglyceride, and/or mixed trig
- Polyethylene glycol 300 BP (humectant) 10.0 2-Phenoxyethanol (Phenoxetol Nipa) 1.0 Carbovinyl crosspolymer (Carbopol 980NF) 0.5 Sodium hydroxide BP pellets (pH adjuster) 0.085
- Example 1 The ingredients above were mixed together to form an opaque gel composition.
- the gel composition of Example 1 was applied to the skin of the ankle of a human volunteer which was itching, had flaky skin and was red and inflamed. The composition was found to reduce the itching sensation and within a short time the skin flakiness. This surprising effect was independent of any anti-inflammatory, anti-pyretic or analgesic response which might be expected to result from application of ibuprofen.
- a guinea pig was suffering from pruritus to the extent that hair was eliminated from the skin and a red patch had developed on the skin the size of a penny. Some of the gel made up as Example 1 was applied to the sore and this was repeated daily for one week. Within this time the red patch disappeared and the hair started to regrow in the affected area. The guinea pig made a continuous recovery without relapse.
- Carboxyvinyl crosspolymer (Carbopol) 2.0 Denatured ethanol (clarifying agent) 5.0 Sodium hydroxide (pH adjuster) 1.525
- Denatured ethanol (clarifying agent) 40 . 0 Carboxyvinyl crosspolymer (Carbopol) 2 . 6 N,N,N',N'-tetrakis (2-hydroxypropyl) ethylene diamine [Quadrol] 9 . . 0 Propylene glycol (humectant) 2 , . 0 Ethoxylated fatty alcohol (Brij 92) 2 . . 0 Purified water (diluent) to 100
Abstract
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Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP94931531A EP0724438A1 (en) | 1993-10-20 | 1994-10-19 | Ibuprofen and flurbiprofen as anti-pruritic agents |
SK488-96A SK48896A3 (en) | 1993-10-20 | 1994-10-19 | Application of ibuprofen and flurbiprofen as anti-pruritic agents and and pharmaceutical compositions for this use |
JP7511332A JPH09504018A (en) | 1993-10-20 | 1994-10-19 | Ibuprofen and flurbiprofen as antipruritic agents |
AU80586/94A AU690155B2 (en) | 1993-10-20 | 1994-10-19 | Ibuprofen and flurbiprofen as anti-pruritic agents |
FI961716A FI961716A (en) | 1993-10-20 | 1996-04-19 | Ibuprofen and flurbiprofen as antipruritic agents |
NO961589A NO961589L (en) | 1993-10-20 | 1996-04-19 | Pharmaceutical mixtures |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9321671.1 | 1993-10-20 | ||
GB939321671A GB9321671D0 (en) | 1993-10-20 | 1993-10-20 | Pharmaceutical composition |
GB9405024A GB9405024D0 (en) | 1994-03-15 | 1994-03-15 | Pharmaceutical composition |
GB9405024.2 | 1994-03-15 | ||
GB9405025.9 | 1994-03-15 | ||
GB9405025A GB9405025D0 (en) | 1994-03-15 | 1994-03-15 | Pharmaceutical composition |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1995011017A1 true WO1995011017A1 (en) | 1995-04-27 |
Family
ID=27266892
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1994/003442 WO1995011017A1 (en) | 1993-10-20 | 1994-10-19 | Ibuprofen and flurbiprofen as anti-pruritic agents |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP0724438A1 (en) |
JP (1) | JPH09504018A (en) |
AU (1) | AU690155B2 (en) |
CA (1) | CA2174619A1 (en) |
CZ (1) | CZ112496A3 (en) |
FI (1) | FI961716A (en) |
HU (1) | HUT74448A (en) |
NO (1) | NO961589L (en) |
PL (1) | PL314036A1 (en) |
SK (1) | SK48896A3 (en) |
WO (1) | WO1995011017A1 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997035573A2 (en) * | 1996-03-27 | 1997-10-02 | The Boots Company Plc | NSAIDs IN THE TREATMENT OF PRURITUS |
EP0897726A1 (en) * | 1996-11-25 | 1999-02-24 | Toray Industries, Inc. | Antipruritic agent |
EP1707199A1 (en) | 2005-03-30 | 2006-10-04 | Astion Development A/S | Oxaprozin or closely related compound for the treatment and prevention of pruritus |
WO2011073998A1 (en) | 2009-12-16 | 2011-06-23 | Shasun Pharmaceuticals Limited | Composition of dexibuprofen transdermal hydrogel |
EP2468270A1 (en) * | 2010-12-21 | 2012-06-27 | GALENpharma GmbH | (R)-2-(3-fluoro-4-phenylphenyl)propionic acid for use in the treatment of skin diseases |
GB2493914A (en) * | 2011-08-19 | 2013-02-27 | Univ Jw Goethe Frankfurt Main | Flurbiprofen and related compounds for the treatment of skin diseases |
CN113262216A (en) * | 2020-02-14 | 2021-08-17 | 北京泰德制药股份有限公司 | External preparation for eliminating skin surface red swelling and easing pain |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101932316A (en) * | 2007-12-21 | 2010-12-29 | Paz医药发展有限公司 | Pharmaceutical preparation and preparation thereof and its application in the relevant neuropathy of treatment pain |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2482456A1 (en) * | 1980-05-14 | 1981-11-20 | Hisamitsu Pharmaceutical Co | GEL COMPOSITION, ANTI-INFLAMMATORY AND ANALGESIC, BASED ON KETOPROFEN AND / OR FLURBIPROFEN |
EP0127840A1 (en) * | 1983-06-01 | 1984-12-12 | Lederle (Japan) Ltd. | Antiinflammatory analgesic gelled ointments |
JPS62223118A (en) * | 1986-03-12 | 1987-10-01 | Hisamitsu Pharmaceut Co Inc | Cream composition for external use |
JPH01224328A (en) * | 1988-03-01 | 1989-09-07 | Kao Corp | Antipruritic agent composition |
EP0439344A2 (en) * | 1990-01-24 | 1991-07-31 | McNEIL-PPC, INC. | Method for percutaneous delivery of ibuprofen using hydroalcoholic gel |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3317124A1 (en) * | 1983-05-07 | 1984-11-08 | Teroson Gmbh, 6900 Heidelberg | DEVICE FOR APPLYING LIQUIDS WITH DIFFERENT CONSISTENCY |
-
1994
- 1994-10-19 AU AU80586/94A patent/AU690155B2/en not_active Ceased
- 1994-10-19 WO PCT/EP1994/003442 patent/WO1995011017A1/en not_active Application Discontinuation
- 1994-10-19 PL PL94314036A patent/PL314036A1/en unknown
- 1994-10-19 SK SK488-96A patent/SK48896A3/en unknown
- 1994-10-19 HU HU9601031A patent/HUT74448A/en unknown
- 1994-10-19 JP JP7511332A patent/JPH09504018A/en active Pending
- 1994-10-19 EP EP94931531A patent/EP0724438A1/en not_active Withdrawn
- 1994-10-19 CA CA002174619A patent/CA2174619A1/en not_active Abandoned
- 1994-10-19 CZ CZ961124A patent/CZ112496A3/en unknown
-
1996
- 1996-04-19 NO NO961589A patent/NO961589L/en unknown
- 1996-04-19 FI FI961716A patent/FI961716A/en unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2482456A1 (en) * | 1980-05-14 | 1981-11-20 | Hisamitsu Pharmaceutical Co | GEL COMPOSITION, ANTI-INFLAMMATORY AND ANALGESIC, BASED ON KETOPROFEN AND / OR FLURBIPROFEN |
EP0127840A1 (en) * | 1983-06-01 | 1984-12-12 | Lederle (Japan) Ltd. | Antiinflammatory analgesic gelled ointments |
JPS62223118A (en) * | 1986-03-12 | 1987-10-01 | Hisamitsu Pharmaceut Co Inc | Cream composition for external use |
JPH01224328A (en) * | 1988-03-01 | 1989-09-07 | Kao Corp | Antipruritic agent composition |
EP0439344A2 (en) * | 1990-01-24 | 1991-07-31 | McNEIL-PPC, INC. | Method for percutaneous delivery of ibuprofen using hydroalcoholic gel |
Non-Patent Citations (12)
Title |
---|
A.B. FLEISCHER ET AL.: "PRURITUS IN THE ELDERLY: MANAGEMENT BY SENIOR DERMATOLOGISTS", JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, vol. 28, no. 4, April 1993 (1993-04-01), pages 603 - 609 * |
A.K. BLACK ET AL.: "THE EFFECT OF TOPICAL FLURBIPROFEN ON HUMAN SKIN INFLAMMATION", BR. J. CLIN. PHARMACOL., vol. 9, no. 1, 1980, pages 125P * |
DATABASE WPI Week 8745, Derwent World Patents Index; AN 87-316438 * |
M.W. GREAVES ET AL.: "ITCH: ROLE OF PROSTAGLANDINS", BRITISH MEDICAL JOURNAL, vol. 3, 1973, pages 608 - 609 * |
M.W. GREAVES ET AL.: "PHARMACOLOGY AND SIGNIFICANCE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN THE TREATMENT OF SKIN DISEASES", JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, vol. 16, no. 4, 1987, pages 751 - 764 * |
O. HAGERMARK ET AL.: "PRURITOGENIC ACTIVITY OF PROSTAGLANDIN E2", ACTA DERMATO-VENEREOLOGICA, vol. 57, no. 1, 1977, pages 37 - 43 * |
PATENT ABSTRACTS OF JAPAN vol. 01, no. 3549 (C - 662) 7 December 1989 (1989-12-07) * |
R.G. TWYCROSS ET AL.: "PRURITUS AND PAIN IN EN CUIRASS BREAST CANCER", THE LANCET, vol. 2, no. 8248, 1981, pages 696 * |
R.K. WINKELMANN: "PHARMACOLOGIC CONTROL OF PRURITUS", THE MEDICAL CLINICS OF NORTH AMERICA, vol. 66, no. 5, 1982, pages 1119 - 1133 * |
R.S.STERN ET AL.: "IBUPROFEN IN THE TREATMENT OF UV-B-INDUCED INFLAMMATION", ARCHIVES OF DERMATOLOGY, vol. 121, no. 4, 1985, pages 508 - 512 * |
S. LAUTENSCHLAGER ET AL.: "DAS SCHNITZLER-SYNDROM", DER HAUTARZT, vol. 44, no. 12, December 1993 (1993-12-01), pages 781 - 784 * |
Y.M. MIRENSKY ET AL.: "THE RED FACE: ATOPIC DERMATITIS", CLINICS IN DERMATOLOGY, vol. 11, no. 2, June 1993 (1993-06-01), pages 235 - 242 * |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997035573A2 (en) * | 1996-03-27 | 1997-10-02 | The Boots Company Plc | NSAIDs IN THE TREATMENT OF PRURITUS |
WO1997035573A3 (en) * | 1996-03-27 | 1997-11-27 | Boots Co Plc | Nsaids in the treatment of pruritus |
EP0897726A1 (en) * | 1996-11-25 | 1999-02-24 | Toray Industries, Inc. | Antipruritic agent |
EP0897726A4 (en) * | 1996-11-25 | 2003-05-28 | Toray Industries | Antipruritic agent |
EP1707199A1 (en) | 2005-03-30 | 2006-10-04 | Astion Development A/S | Oxaprozin or closely related compound for the treatment and prevention of pruritus |
EP2512446A4 (en) * | 2009-12-16 | 2012-10-24 | Shasun Pharmaceuticals Ltd | Composition of dexibuprofen transdermal hydrogel |
CN102665681A (en) * | 2009-12-16 | 2012-09-12 | 厦桑医药有限公司 | Composition of dexibuprofen transdermal hydrogel |
WO2011073998A1 (en) | 2009-12-16 | 2011-06-23 | Shasun Pharmaceuticals Limited | Composition of dexibuprofen transdermal hydrogel |
EP2512446A1 (en) * | 2009-12-16 | 2012-10-24 | Shasun Pharmaceuticals Limited | Composition of dexibuprofen transdermal hydrogel |
AU2010331761B2 (en) * | 2009-12-16 | 2015-09-24 | Strides Pharma Science Limited | Composition of dexibuprofen transdermal hydrogel |
EP2468270A1 (en) * | 2010-12-21 | 2012-06-27 | GALENpharma GmbH | (R)-2-(3-fluoro-4-phenylphenyl)propionic acid for use in the treatment of skin diseases |
WO2012084978A1 (en) | 2010-12-21 | 2012-06-28 | Galenpharma Gmbh | (r)-2-(3-fluoro-4-phenylphenyl)propionic acid for use in the treatment of skin diseases |
GB2493914A (en) * | 2011-08-19 | 2013-02-27 | Univ Jw Goethe Frankfurt Main | Flurbiprofen and related compounds for the treatment of skin diseases |
WO2013026772A1 (en) * | 2011-08-19 | 2013-02-28 | Johann Wolfgang Goethe-Universität | Flurbiprofen and related compounds for the treatment of skin diseases |
CN113262216A (en) * | 2020-02-14 | 2021-08-17 | 北京泰德制药股份有限公司 | External preparation for eliminating skin surface red swelling and easing pain |
Also Published As
Publication number | Publication date |
---|---|
EP0724438A1 (en) | 1996-08-07 |
NO961589L (en) | 1996-06-17 |
CZ112496A3 (en) | 1997-04-16 |
FI961716A (en) | 1996-06-03 |
NO961589D0 (en) | 1996-04-19 |
FI961716A0 (en) | 1996-04-19 |
HU9601031D0 (en) | 1996-06-28 |
JPH09504018A (en) | 1997-04-22 |
CA2174619A1 (en) | 1995-04-27 |
PL314036A1 (en) | 1996-08-05 |
AU690155B2 (en) | 1998-04-23 |
HUT74448A (en) | 1996-12-30 |
AU8058694A (en) | 1995-05-08 |
SK48896A3 (en) | 1997-03-05 |
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