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WO2003086348A1 - Formulation et methode de traitement de la dermatite allergique - Google Patents

Formulation et methode de traitement de la dermatite allergique Download PDF

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Publication number
WO2003086348A1
WO2003086348A1 PCT/AU2003/000424 AU0300424W WO03086348A1 WO 2003086348 A1 WO2003086348 A1 WO 2003086348A1 AU 0300424 W AU0300424 W AU 0300424W WO 03086348 A1 WO03086348 A1 WO 03086348A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical formulation
topically administrable
formulation
administrable pharmaceutical
weight
Prior art date
Application number
PCT/AU2003/000424
Other languages
English (en)
Inventor
Kivalur Swaminathan
Kenneth Vincent Mason
Original Assignee
Dermcare-Vet Pty Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Dermcare-Vet Pty Ltd filed Critical Dermcare-Vet Pty Ltd
Priority to AU2003213869A priority Critical patent/AU2003213869A1/en
Publication of WO2003086348A1 publication Critical patent/WO2003086348A1/fr

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Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • 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
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • TREATMENT FIELD OF THE INVENTION relates to formulations for topical application of anti- inflammatory steroids alone or in combination with anti-bacterial or antifungal drugs.
  • the formulations are useful for a variety of skin conditions due to the tolerance, efficacy and ease of use and application over large affected areas of the skin of both haired and non-haired animals.
  • Conditions treated by the present invention include allergic dermatitis, inclusive of contact dermatitis, atopic dermatitis, and secondary complications in the form of bacterial infections such as by Staphylococcus species and fungal/yeast infections such as caused by Malassezia species.
  • Atopic dermatitis is a genetically predisposed inflammatory and pruritic skin disease with characteristic clinical features. It is a well recognized disease in man and dogs but poorly understood in other mammals.
  • Atopic dermatitis is associated most commonly but not exclusively with immediate type hypersensitivity characterized by the production of IgE antibodies to environmental allergens.
  • Affected animals and man can have associated food allergies and commonly develop secondary infections with skin and mucosal commensal organisms namely the bacteria Staphylococcus spp. and the yeast Malassezia spp.
  • Topical formulations of corticosteroids have been known since the 1950s as treatment for various inflammatory skin conditions such as atopic dermatitis, eczema etc. Topical steroidal preparations are also used in combination with antibacterial or antifungal agents in disease conditions that include an inflammatory component but all have been limited by practicality to non haired skin.
  • formulations of topical steroids have involved suspensions or solutions of the steroid substance in vehicles that are based on oils, waxes or organic solvents.
  • United States Patent 5,958,391 recites a formulation that comprises 0.5-2.5% hydrocortisone (HC), 2.5-7.5% elemental sulfur, 90-97% in a vehicle which is hydrocarbon jelly and aqueous carboxypolymethylene. This is intended for scalp application.
  • HC hydrocortisone
  • elemental sulfur 90-97%
  • vehicle which is hydrocarbon jelly
  • carboxypolymethylene This is intended for scalp application.
  • United States Patent 4,918,065 describes a cream or ointment type of formulation of a steroid dispersed in a base consisting of both a water/oil and an oil/water emulsion with high proportions of waxy substances
  • United States Patent 4,738, 956 discloses pharmaceutical preparations with a mix of 20-40% fatty alcohol (C 12-22), 30- 60% of volatile silicone, 0.1-10% hydrocortisone and preservative, emulsifier etc. The aim was to provide a silky non-greasy delivery system capable of spreading the ingredient smoothly and evenly without leaving a residue and increasing percutaneous absorption and bioavailability.
  • United States Patent 4,370,322 there are described steroid formulations with only fatty substances as vehicle, such as dibutyl adipate, isopropyl myristate, wax and paraffin oil.
  • United States Patent 4,363,806 describes and claims a formulation of steroid in a multiple emulsion vehicle which is a hydrophilic solvent-in-oil-in- water emulsion.
  • the steroid is dissolved in propylene glycol (PG) and emulsified in an oil phase.
  • PG propylene glycol
  • the solvent-in-oil emulsion is emulsified in an aqueous solution giving rise to the emulsion.
  • Another type of formulation uses organic solvents such as alkanols and polyhydric alcohols.
  • organic solvents such as alkanols and polyhydric alcohols.
  • United States Patent 3,899,580 describes topical corticosteroid formulations containing only 8-18% water and 60-90% solvents such as ethanol, PG and glycerine.
  • United States Patent 4,353,896 describes a topical steroid formulation prepared in 15% dimethylsulphoxide as solvent as well as 10% isopropyl alcohol (IP A).
  • prior art formulations are typically based on viscous, solid or semisolid waxes and fatty ingredients and therefore in application to large areas of the skin or skin surfaces that are covered in hair, these prior art formulations do not lend themselves to even and extensive application. This results in poor appearance of skin and/or hair (such as matting of hair, stickiness, greasy appearance, smearing to surfaces that come in contact, loss of dosage by these means etc).
  • the active ingredients in some cases are not dissolved and are subject to loss or poor bioavailability.
  • Many formulations are based on high proportions of organic solvents such as ethanol, propylene glycol, isopropyl alochol and polyethylene glycol. These solvents either tend to irritate the skin or leave a greasy appearance on application.
  • corticosteroids while useful in treating inflammatory skin conditions can have, in addition, undesirable side effects due to systemic absorption.
  • the suppression of the HPA axis (hypothalamic-pituitary-adrenal) by systemic availability of steroids is well known.
  • Other potential side affects are Gushing' s syndrome, glucosuria and hyperglycemia. The risk of side affects increase in cases where anti-inflammatory treatment is required over large areas of skin.
  • the method and formulation of the present invention has overcome this problem and is a superior alternative to systemic corticosteroid treatment in the treatment of haired animals (mammals) with allergic dermatitis without the danger of systemic toxic side effects of corticosteroids.
  • Another object of the invention is to provide a formulation that has low amounts of waxy, oily and solid substances and solvents to minimize greasy feel, and that avoids accidental removal of product by contacting surfaces and irritation and drying of skin due to solvents. Practically this formulation and method relies on being applied after a shampoo and to the wet hair. Thus aiding in the spreadability and retaining the moisture in the skin and hair and even replacing shampoo removed sebum and natural conditioning oils.
  • a further object of the invention is to provide a method for treatment of haired skin and non-hair skin with a topically administered formulation of a steroid either alone or in combination with an anti-bacterial and/or an antifungal agent.
  • the invention provides a topically administrable pharmaceutical formulation comprising:
  • the topical formulation further comprises a therapeutically effective amount of an anti-bacterial, antiseptic or antifungal agent at 0.1-5% by weight of the formulation.
  • the topically administrable pharmaceutical further comprises at least one other pharmaceutically acceptable carrier, diluent and/or excipient.
  • Said at least one other pharmaceutically acceptable carrier, diluent and/or excipient may include one or more of a solubilizer, emollient, moisturizer, hair and skin conditioner, preservative and/or stabilizer as are well understood in the art.
  • topical formulations of the invention may be provided as mousse, gels, creams, lotions, foams, shampoos, liquids, aerosols and the like.
  • the topical formulation is a gel or lotion.
  • the present invention provides a formulation in the form of an anti-inflammatory gel for topical application.
  • the formulation comprises a topical anti-inflammatory steroid at 0.01-2% by weight, a polyethoxylated fatty acid ester at 1-15%) by weight, a solubilizing agent such as
  • N-methylpyrrolidinone or propylene carbonate at 2-15% by weight, an aliphatic diol such as propylene glycol at 2-12% by weight, an aliphatic polyol such as polyethylene glycol 400 at 1-6% by weight, a skin and hair conditioner such as polyquaternium, at least one preservative, at least one stabilizer, at least one gelling agent and 50-80% by weight water.
  • an aliphatic diol such as propylene glycol at 2-12% by weight
  • an aliphatic polyol such as polyethylene glycol 400 at 1-6% by weight
  • a skin and hair conditioner such as polyquaternium
  • at least one preservative at least one stabilizer
  • at least one gelling agent at least one gelling agent and 50-80% by weight water.
  • the invention provides a method of treatment of allergic dermatitis in an animal, said method including the step of topically administering the pharmaceutical formulation of the first-mentioned aspect to said animal.
  • the invention provides a method of treatment of allergic dermatitis in an animal, said method including the step of topically administering an anti-inflammatory pharmaceutical formulation to a wet hair or wet skin surface of said animal.
  • the method of the invention provides topical administration to skin and/or hair surfaces of an animal.
  • a particular advantage is that the skin and/or hair surface may be wet.
  • the animal is a mammal.
  • the animal is a companion animal such as a dog, cat, horse, rabbit and the like.
  • the method includes topical administration of an antifungal compound and/or an anti-bacterial compound to treat secondary complications of allergy.
  • secondary complications include bacterial infections such as by Staphylococcus species and fungal/yeast infections such as by Malassezia species.
  • the formulation of the invention is substantially free of oils, waxes, fats and organic solvents.
  • the formulation is easy to use and spread evenly, leaves only a small amount of residue due to evaporation and absorption of the liquid components and lends a silky, smooth, pleasant feel to the skin and hair.
  • the present inventors have surprisingly created a formulation which, when applied to wet hair after a shampoo bath, can effectively treat all the symptoms of allergic dermatitis and its complicating infections without the need for systemic administration and thereby avoids systemic toxic side effects of the pharmacologically-active ingredients.
  • a topically active steroid can be formulated in a dissolved state either alone or in combination with an antibacterial or antifungal substance into a semi-solid formulation.
  • the active drug substances are maintained in solution within the formulation despite usage of low levels of solubilizing excipients and solvents.
  • the present invention provides a formulation and method for treating allergic dermatitis such as to a food or environmental component acting as a sensitizer, including but not limited to food allergy, atopic dermatitis, insect bite allergy and contact dermatitis.
  • associated conditions include intertrigo, Malassezia and fungal dermatitis, and/or Staphylococcus dermatitis.
  • the present invention provides a new method of treating allergic dermatitis and secondary complications thereof, especially in animals having haired skin, by applying a formulation to wet hair.
  • the treatment of the present invention would, in the preferred course of events, occur after a shampoo bath and after rinsing the suds off, the formulation of the invention then applied to the wet coat/hair.
  • the formulation with the anti-inflammatory steroid and any antimicrobial compound, if needed will penetrate the haired coat and deposit the pharmaceutical active onto the skin to have its desired effect.
  • the method of the invention thereby enables total coverage of animals that are covered all over with hair.
  • the same treatment may be used in a conventional method of being applied to non-haired skin.
  • a formulation in accordance with the present invention is provided for the treatment of infections and inflammatory conditions of the skin.
  • the formulation preferably has the semi-solid consistency of a mousse, gel, cream or lotion for ease of storage and application.
  • the formulation of the present invention comprises from 0.01% to 2.0% by weight of an anti-inflammatory steroid.
  • the steroid drugs that may be used in the formulation are exemplified but not limited to betamethasone, hydrocortisone, clobetasol, fluocinolide, triamcinolone, mometasone, fluticasone, desonide, prednisolone, methyl prednisolone, dexamethasone and their salts and derivatives such as furoate, propionate dipropionate, valerate and other alkyl esters.
  • Preferred antiinflammatory steroids include but are not limited to prednisolone, methylprednisolone, hydrocortisone, mometasone and their salts and derivatives.
  • mometasone is mometasone furoate.
  • mometasone is at a concentration of 0.05-0.2% by weight.
  • mometasone is at a concentration of about 0.1 % by weight.
  • prednisolone is present at a concentration of 0.1- 0.3% by weight.
  • prednisolone is at a concentration of about 0.2 % by weight.
  • the formulation may also include an antifungal compound.
  • an antifungal compound included in the scope of the invention are known (imidazole/triazole) antifungal agents such as miconazole, ketoconazole, clotrimazole, enilconazole, econazole, sulconazole, itraconazole, allylamine antifungals such as terbinafine, and butenafine and other antifungals such as nystatin, amphotericin and griseofulvin and their derivatives.
  • the formulation may also include an anti-bacterial/antiseptic compound such as the antiseptic/antibacterials of all the guanidine classes, for example hexetidine, chlorhexidine, polyhexamethylene biguanide antibacterials/antiseptics of the phenolic class such as triclosan, o-chloro-m-cresol, o-, m-, p-xylenols, phenoxyethanol, and iodophors such as iodine, povidone-iodine complexes and iodine salts.
  • an anti-bacterial/antiseptic compound such as the antiseptic/antibacterials of all the guanidine classes, for example hexetidine, chlorhexidine, polyhexamethylene biguanide antibacterials/antiseptics of the phenolic class such as triclosan, o-chloro-m-cresol, o-, m-, p-xylenols, phen
  • the formulation preferably comprises at least one solubilizing excipient from the class of polyethoxylated hydroxy fatty acid esters.
  • polyethoxylated hydroxy fatty acid esters substances obtained by reacting varying amounts of ethylene oxide with hydroxy fatty acid esters.
  • the excipient is one or more of substances obtained by reacting varying amounts of ethylene oxide with either castor oil or hydrogenated castor oil. More preferably, the solubilizing excipient is one or more of ricinoleyl glycerol nominally ethoxylated with 30-50 moles of ethylene oxide and trihydroxystearyl glycerol nominally ethoxylated with 7-60 moles of ethylene oxide.
  • ricinoleyl glycerol nominally ethoxylated with 30-50 moles of ethylene oxide
  • trihydroxystearyl glycerol nominally ethoxylated with 7-60 moles of ethylene oxide.
  • polyethoxylated hydroxy fatty acid esters are commercially available as mixtures and fractions of partially purified formulations.
  • Commercially available products useful in this invention are for example obtainable under the trade names Cremophor from BASF and Croduret from Croda Surfactants.
  • the polyethoxylated hydroxy fatty acid ester excipient is included at a level sufficient to solubilise and maintain in solution the therapeutically active compounds in the final formulation.
  • the polyoxyl (n) hydrogenated castor oil excipient is selected from the group consisting of polyoxyl 35 hydrogenated castor oil, polyoxyl 40 hydrogenated castor oil and polyoxyl 60 hydrogenated castor oil.
  • the polyoxyl (n) hydrogenated castor oil is used at a level of 1- 15% by weight of the total formulation. More preferably, the polyoxyl (n) hydrogenated castor oil is used at a level of 2-10% by weight of the total formulation.
  • the pharmaceutical formulation of the invention may further comprise at least one other pharmaceutically acceptable carrier, diluent or excipient.
  • diluent or excipient include but are not limited to an effective amount of a moisturising, solubilising and substantive ingredient.
  • solubilizing agents such as N-methylpyrrolidinone or propylene carbonate and polyols such as propylene glycol, butylene glycol, hexylene glycol, sorbitol and polyethylene glycol of molecular weights up to 800. More preferably, N-methylpyrrolidinone propylene glycol and polyethylene glycol 400 are used for the purpose.
  • the levels of incorporation of N-methylpyrrolidinone and propylene glycol are preferably from 2-15% by weight. Even more preferably, N-methylpyrrolidinone is included at 2-12% by weight.
  • Polyethylene glycol is preferably present at 1-10% by weight. .
  • the formulation of the present invention may further comprise one or more volatile silicones and/or silicone gums.
  • volatile silicones are octamethylcyclotetrasiloxane, and decamethylcyclopentasiloxane. These are commercially available by the name of cyclomethicone.
  • Preferred cyclomethicones are, for example, available under the trade names Dow Corning 244, 245, 344 and 345 fluids.
  • the silicone gums included in the formulation are preferably ultra-high viscosity polydimethylsiloxanes which are either trimethylsilyl or dimethylsilanol end-blocked. These are known as dimethicone and dimethiconol respectively. Commercially, the dimethicone and dimethiconol are available in blended form with volatile cyclomethicones. Suitable silicone gum blends are for example available under the trade names Dow Corning 1401, 1404, 1411 and 1501 fluids. Other mixtures of volatile cyclomethicones, dimethicones and dimethiconols known to those skilled in the art may also be used in the formulation to obtain the desired cosmetic effect. These are included within the scope of the present invention.
  • the volatile cyclomethicone is included in the formulation preferably at a level of 1-12%, more preferably at 4-8% by weight.
  • the silicone gum is incorporated within the formulation preferably at a level of 0.1-6%) and more preferably at 0.4-2.0% by weight.
  • an effective amount of a thickener may be incorporated within the formulation to obtain the desired viscosity and consistency of the product.
  • Suitable thickening agents for the purpose of the invention are acrylate polymers and co-polymers among the classes of polyacrylates, polymethacrylate, polymethylmethacrylates, polyacrylamides and their cross-linked derivatives, cellulose derivatives such as methyl cellulose, hydroxyethyl cellulose, hydroxypropylmehyl cellulose, and hydroxypropyl cellulose, naturally derived gums such as xanthan gum, acacia gum, carob gum, alginate derivatives and pectin.
  • the thickener is one or more of a cross-linked polyacrylic acid derivative, a polyacrylamide derivative or a cationic polyacrylate derivative.
  • suitable thickeners are available under the trade names of Salcare SC92, Salcare SC96 (Ciba Speciality Chemicals), Carbopol and Permulen (E F Goodrich), Aculyn 33 A, Aculyn 44 (Rohm and Haas), Methicel (The Dow Chemical Company) and Sepigel 305 (Seppic).
  • the thickener is incorporated in an amount suitable to obtain the desired thickening effect.
  • the thickener is used at a level of 0.1-8% by weight of the formulation. More preferably the thickener is incorporated at a level of 1- 5% in the composition.
  • ingredients such as hair and skin conditioners, metal chelates, antioxidants, pH modifiers, perfumes and colours may be included within the formulation.
  • Suitable hair and skin conditioners are low molecular weight and polymeric quaternary ammonium salts.
  • the low molecular weight quaternary ammonium salts are well established in use as conditioning agents in the cosmetic industry.
  • Suitable quaternary salts are, cetrimonium chloride, benzalkonium chloride, steartrimonium chloride, cocotrimonium chloride and so forth.
  • Polymeric quaternary ammonium compounds commonly known as polyquatemium (CTFA adopted names) such as Polyquatemium 11 (quaternized copolymers of vinylpyrrolidone and dimethylaminoethyl methacrylate), Polyquatenium 7 (diallyl dimethyl ammonium chloride and acrylamide copolymer), Polyquatemium 37, Polyquatemium 32 are also suitable for use. These conditioners are used at a level of 0.1 -8%, more preferably at a level of 0.5- 3% by weight of dry substance.
  • a suitable metal chelant for use in the formulation is ethylene diamine tetraacetic acid (EDTA) or any of its salts such as sodium salt, potassium salt, ammonium salt and triethanolammonium salt, typically used at a level of 0.01 to 0.2% by weight of the formulation.
  • EDTA ethylene diamine tetraacetic acid
  • any of its salts such as sodium salt, potassium salt, ammonium salt and triethanolammonium salt, typically used at a level of 0.01 to 0.2% by weight of the formulation.
  • an effective amount of antioxidant such as butyrated hydroxy anisole, butyrated hydroxy toluene or propyl gallate may be used at an effective dose to prevent oxidative degradation of the drug substances.
  • the antioxidant is incorporated at 0.002-0.2% by weight of product.
  • a pH adjuster or neutralizer by which terms is implied an acid or base for regulating the pH of the formulation may be used to adjust the pH of the formulation to a range of 4-8, and preferably 5.5-7.0.
  • the base used is for example, the hydroxide, carbonate, bicarbonate of sodium, potassium or ammonium or triethanolamine.
  • An effective amount of preservative may also be included in to protect the formulation from spoilage during the shelf life of the product.
  • Suitable preservatives are 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methy-4- isothiazoline-3-one, l,3-bis(hydroxymethyl)-5,5-dimethylhydantoin, sodium hydroxymethylglycinate, diazolidinyl urea, methyl paraben, propyl paraben, 2- bromo-2-nitropropane-l,3-diol, sorbic acid and benzyl alcohol.
  • suitable oil and wax components may be included in the formulation of the invention to facilitate refatting and to relieve skin dryness.
  • Several natural and semisynthetic glyceride esters and waxes are readily available to the skilled person.
  • Suitable amounts of a pigment, colouring agent or perfume may be used to confer desirable usage characteristics to the product.
  • a substantial portion of the formulation is water as the vehicle for the ingredients. Water preferably comprises 50-80% by weight or more preferably 60- 75% of the formulation of the invention.
  • the formulation of the invention is manufactured by the usual methods of dissolution, blending and mixing operations as are well known in the art of pharmaceutical and cosmetic manufacture.
  • topical formulations of this invention may be provided as mousse, gels, creams, lotions, foams, shampoos, liquids, aerosols and the like.
  • Example 1 A 0.2% prednisolone cream was prepared as per the following formulation (Table 1).
  • prednisolone, propylene glycol, polyethylene glycol 400 Cremophor RH40 and EDTA were weighed, 240g deionised water added and the mixture adjusted to pH 6.5 with triethanolamine and heated to 60- 70°C on a water bath with stirring until a clear solution was obtained. The mixture was then cooled to room temperature and 1300 g of deionised water added and stirred to obtain a clear solution. The required amounts of Salcare super 7 and Kathon CG was added and mixed.
  • the silicone mixture was then added in a slow stream to the formulation with rapid stirring.
  • the formulation was then made to a total amount of 500g with purified water. Stirring was continued intermittently until a smooth cream was formed.
  • Example 3 Formulation of the mometasone furoate composition set forth in Table 3 is as follows.
  • Cremophor RH40, N-methyl pyrrolidone, propylene glycol, polyethylene glycol 400, propyl gallate and BHT were weighed into a suitable vessel and heated to 45°C for 48 hrs.
  • EDTA was suspended in 500 g of water in a second container and neutralised with stirring by addition of triethanolamine until dissolved. The pH of this solution was adjusted to 5.0 with orthophosphoric acid. Salcare Super 7 was added and mixed till dissoled. Titanium dioxide was added and the mixture homogenised at 4000 rpm for 5 minutes (suspension B).
  • Capric/caprylic triglyceride, acetylated lanolin and phenoxyethanol were wighed into a third container and heated with mixing till a homogeneous mixture was obtained (mixture C).
  • a fourth container was charged with silicone 1401, silicone 245 and sepigel 305. The contents were mixed until homogeneous (mixture D).
  • Example 1 Four cases of dogs with allergic dermatitis were treated with the formulation of Example 1 and two dogs with secondary complications, were treated with the formulation described in Example 2.
  • Example 3 Four cases of dogs with allergic dermatitis were treated with the formulation in Example 3.
  • the clinical signs (erythema, pruritus, ear inflammation, scale and alopecia) were each graded on a linear scale of 0 to 5 (to a cumulative score of 0-25).
  • Allergic dogs were graded and treated according to the formulation and method of the invention once weekly for 4 to 8 weeks then re-examined and graded.
  • the aggregate scores before and after are provided in Table 4.
  • Example 1 and Example 3 Two cases (the first shown in Table 4) of dogs being treated for allergic dermatitis for 2 months with once weekly application of the formulation of Example 1 and Example 3 used as an after shampoo lotion had blood samples drawn for multiple biochemical analysis for organ function (particularly liver and kidney) and adrenal function test of the adrenal pituitary axis function (ACTH, Adrenocorticotropin stimulation test). The biochemical parameters of organ function and damage indicators, and the adrenal -pituitary axis were found to be normal.
  • compositions according to the present invention provide many advantages over the prior art. They may be applied over a large area of hair- covered or skin surfaces of an animal and thereby treat both allergic dermatitis and secondary conditions as hereinbefore described. Being essentially water-based, the pharmaceutical formulation of the invention is non-greasy, non-occlusive and provides a cosmetically appealing appearance after administration to an animal. The moisturising properties of the pharmaceutical formulation act to improve the feel of the animals skin after application.
  • concentrations of ingredients may be readily varied by the skilled person. It will also be appreciated that concentrations expressed in the range x-y% include all ranges within the stated range. Preferably, the ranges are integer ranges.

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Abstract

L'invention concerne des formulations et des méthodes de traitement pour l'application topique sur des animaux de stéroïdes anti-inflammatoires seuls ou en combinaison avec des médicaments antibactériens ou antifongiques. La formulation contient un dérivé polyéthoxylé d'un ester d'acide gras procurant une sensation douce et non grasse à la formulation administrée par voie topique. Cette formulation peut traiter diverses pathologies de la peau en raison de la tolérance, de l'efficacité et de la simplicité d'utilisation et d'application sur de larges zones affectées de la peau d'animaux à poils ou sans poils. Parmi les pathologies traitées par cette formulation figurent la dermatite allergique, y compris la dermatite de contact, l'atopie de contact, la dermatite atopique, ainsi que des complications secondaires sous forme d'infections bactériennes telles que par des espèces de staphylocoques et d'infections fongiques/aux levures telles que celles causées par des espèces de Malassezia.
PCT/AU2003/000424 2002-04-08 2003-04-08 Formulation et methode de traitement de la dermatite allergique WO2003086348A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003213869A AU2003213869A1 (en) 2002-04-08 2003-04-08 Allergic dermatitis formulation and method of treatment

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPS1585A AUPS158502A0 (en) 2002-04-08 2002-04-08 Allergic dermatitis composition and method of treatment
AUPS1585 2002-04-08

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EP1574222A1 (fr) * 2004-03-12 2005-09-14 Cipla Ltd. Procédé de stérilisation
WO2005097094A1 (fr) * 2004-04-08 2005-10-20 Dermcare-Vet Pty Ltd Compositions antimicrobiennes et leurs methodes d'utilisation
WO2006031848A2 (fr) * 2004-09-15 2006-03-23 Ivax Corporation Corticosteroide ayant une faible absorption systemique
WO2007104895A1 (fr) * 2006-03-15 2007-09-20 Galderma S.A. Compositions topiques sous forme d' emulsion h/e comprenant un glycol pro- penetrant et un anti- inflammatoire steroidien
EP2120868A2 (fr) * 2007-04-11 2009-11-25 Perrigo Israel Phamaceuticals Ltd. Préparations de mométasone à faible dose
AU2005230209B2 (en) * 2004-04-08 2010-06-24 Dermcare-Vet Pty Ltd Antimicrobial compositions and methods for their use
WO2010122474A2 (fr) * 2009-04-20 2010-10-28 Sulur Subramaniam Vanangamudi Crème médicinale antifongique et stéroïdique incorporant un biopolymère, et son procédé de fabrication
US20120238535A1 (en) * 2009-02-23 2012-09-20 Smith Jan G Topical formulation of low level clobetasol propionate for treating disorders of the skin and mucous membranes
US11439682B2 (en) 2017-10-31 2022-09-13 Oneness Biotech Co., Ltd. Treating IgE-mediated allergic diseases
RU2800765C2 (ru) * 2017-10-31 2023-07-27 Ваннесс Биотек Ко. Лтд. ЛЕЧЕНИЕ АЛЛЕРГИЧЕСКИХ ЗАБОЛЕВАНИЙ, ОПОСРЕДОВАННЫХ IgE
EP4034130A4 (fr) * 2019-09-23 2023-10-18 Dermcare-Vet Pty Ltd Composés pharmaceutiques et procédés d'utilisation
WO2024015595A1 (fr) * 2022-07-14 2024-01-18 Vetnique Labs, Llc Compositions pour le traitement d'affections de l'oreille

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Cited By (22)

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Publication number Priority date Publication date Assignee Title
US7892483B2 (en) 2004-03-12 2011-02-22 Cipla Limited Sterilization process
EP1574222A1 (fr) * 2004-03-12 2005-09-14 Cipla Ltd. Procédé de stérilisation
WO2005097094A1 (fr) * 2004-04-08 2005-10-20 Dermcare-Vet Pty Ltd Compositions antimicrobiennes et leurs methodes d'utilisation
US9814688B2 (en) 2004-04-08 2017-11-14 Dermcare-Vet Pty Ltd Antimicrobial compositions and methods for their use
US9555015B2 (en) 2004-04-08 2017-01-31 Dermcare-Vet Pty Ltd Antimicrobial compositions and methods for their use
AU2005230209B2 (en) * 2004-04-08 2010-06-24 Dermcare-Vet Pty Ltd Antimicrobial compositions and methods for their use
WO2006031848A2 (fr) * 2004-09-15 2006-03-23 Ivax Corporation Corticosteroide ayant une faible absorption systemique
WO2006031848A3 (fr) * 2004-09-15 2006-06-01 Ivax Corp Corticosteroide ayant une faible absorption systemique
US8653055B2 (en) 2004-09-15 2014-02-18 Teva Animal Health, Inc. Corticosteroid having low systemic absorption
FR2898498A1 (fr) * 2006-03-15 2007-09-21 Galderma Sa Nouvelles compositions topiques sous forme d'emulsion h/e comprenant un glycol pro-penetrant
US8551503B2 (en) 2006-03-15 2013-10-08 Galderma S.A. Topical anti-inflammatory compositions comprising O/W emulsions containing pro-penetrating glycols
WO2007104895A1 (fr) * 2006-03-15 2007-09-20 Galderma S.A. Compositions topiques sous forme d' emulsion h/e comprenant un glycol pro- penetrant et un anti- inflammatoire steroidien
EP2120868A4 (fr) * 2007-04-11 2010-08-25 Perrigo Israel Phamaceuticals Préparations de mométasone à faible dose
EP2120868A2 (fr) * 2007-04-11 2009-11-25 Perrigo Israel Phamaceuticals Ltd. Préparations de mométasone à faible dose
US20120238535A1 (en) * 2009-02-23 2012-09-20 Smith Jan G Topical formulation of low level clobetasol propionate for treating disorders of the skin and mucous membranes
WO2010122474A3 (fr) * 2009-04-20 2010-12-29 Sulur Subramaniam Vanangamudi Crème médicinale antifongique et stéroïdique incorporant un biopolymère, et son procédé de fabrication
WO2010122474A2 (fr) * 2009-04-20 2010-10-28 Sulur Subramaniam Vanangamudi Crème médicinale antifongique et stéroïdique incorporant un biopolymère, et son procédé de fabrication
US11439682B2 (en) 2017-10-31 2022-09-13 Oneness Biotech Co., Ltd. Treating IgE-mediated allergic diseases
RU2800765C2 (ru) * 2017-10-31 2023-07-27 Ваннесс Биотек Ко. Лтд. ЛЕЧЕНИЕ АЛЛЕРГИЧЕСКИХ ЗАБОЛЕВАНИЙ, ОПОСРЕДОВАННЫХ IgE
US12083161B2 (en) 2017-10-31 2024-09-10 Oneness Biotech Co., Ltd. Treating IgE-mediated allergic diseases
EP4034130A4 (fr) * 2019-09-23 2023-10-18 Dermcare-Vet Pty Ltd Composés pharmaceutiques et procédés d'utilisation
WO2024015595A1 (fr) * 2022-07-14 2024-01-18 Vetnique Labs, Llc Compositions pour le traitement d'affections de l'oreille

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