Claims for Patent: 9,498,465

Summary for Patent: 9,498,465

Title:	Topical compositions in the form of a gel containing a particular solubilized retinoid
Abstract:	A composition in the form of a gel, preferably hydroglycolic, is described. The composition can include in a physiologically acceptable medium, at least one particular retinoid. Also described, is a method for the preparation thereof and the cosmetic and dermatological use of the same.
Inventor(s):	Duprat; Agnes (Mougins, FR), Mallard; Claire (Mougins, FR)
Assignee:	GALDERMA RESEARCH & DEVELOPMENT (Boit, FR)
Application Number:	14/404,913
Patent Claims:	1. A pharmaceutical composition comprising at least one active agent represented by a compound of general formula (I) ##STR00011## wherein R.sub.1 is a hydrogen atom, an alkyl radical having from 1 to 4 carbon atoms or a --CF.sub.3 radical; R.sub.2 is a hydrogen atom, an alkyl or alkoxy radical having from 1 to 4 carbon atoms or a chlorine atom; R.sub.3 is a hydrogen atom, or a linear or branched alkyl or alkoxy radical having from 1 to 10 carbon atoms, optionally substituted with a methoxy group; R.sub.4 is a hydrogen atom or an alkyl radical having from 1 to 3 carbon atoms; R.sub.5 is a hydrogen atom or an alkyl radical having from 1 to 3 carbon atoms; or else R.sub.4 and R.sub.5 form, together with the --N--C(.dbd.Y)-- bond, a ring of pyrrolidine, pyrrolidinone, piperidine or piperidinone ring; Y represents two hydrogen atoms or a heteroatom; Ar represents a 1,4-phenyl, 2,5-pyridyl, 5,2-pyridyl or 2,5-thiophenyl ring; X represents a C--C single bond or an oxygen atom optionally substituted with an alkyl or alkylamine chain; A represents a hydrogen atom or the formula below: ##STR00012## wherein Q is an oxygen atom or the --NH-- bond; R.sub.6 represents a hydrogen atom, an alkyl radical having from 1 to 6 carbon atoms, a cycloalkyl radical having from 3 to 6 carbon atoms, or a --C(O)CH.sub.2 or --C(O)CH.sub.2CH.sub.3 radical; R.sub.7 and R.sub.7' represent, independently of one another, a hydrogen atom or a hydroxyl group, on the condition that R.sub.7 and R.sub.7' are not simultaneously a hydroxyl group; n is 0, 1, 2, 3, 4 or 5; water, at least one gelling agent, at least one hydrophilic solvent and at least one hydrophilic cosolvent, wherein the compound of formula (I) is soluble in the hydrophilic solvent and the hydrophilic cosolvent, and wherein the hydrophilic solvent is selected from the group consisting of methylpyrrolidone, ethoxydiglycol, benzyl alcohol, polyethylene glycol, phenoxyethanol, ethanol, and mixtures thereof. 2. The composition as claimed in claim 1, wherein the compound of general formula (I) is defined such that: R.sub.1 is a hydrogen atom, a t-butyl radical or an i-propyl radical; R.sub.2 is a hydrogen atom, a t-butyl radical or an i-propyl radical; R.sub.3 is a hydrogen atom or an ethyl radical; R.sub.4 and R.sub.5 are, independently of one another, a methyl or ethyl radical or else together form a pyrrolidine ring; and A is as defined previously, wherein R.sub.6 represents a hydrogen atom, an i-propyl radical or a t-butyl radical, a cycloalkyl radical having from 3 to 6 carbon atoms, or a --C(O)CH.sub.2 or --C(O)CH.sub.2CH.sub.3 radical. 3. The composition as claimed in claim 1, wherein the compound is 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid. 4. The composition as claimed in claim 1, wherein the composition is an aqueous-glycolic gel in which the active agent is solubilized. 5. The composition as claimed in claim 1, wherein the gelling agent is selected from the group consisting of: polymers of vegetable origin, gums, pectins, cellulose, polymers of microbiological origin, and gelling polymers of synthetic origin. 6. The composition as claimed in claim 1, wherein the hydrophilic solvent is phenoxyethanol, ethanol or a mixture of phenoxyethanol and ethanol. 7. The composition as claimed in claim 1, wherein the cosolvent is a glycol. 8. The composition as claimed in claim 1, wherein the composition also comprises one or more additives selected from the group consisting of: one or more preserving agents; one or more agents for improving the properties of the formulae on application; one or more chelating agents; one or more antioxidants; and one or more soothing agents and/or anti-irritants. 9. The composition as claimed in claim 1, wherein the composition comprises the following ingredients: from 0.00001% to 1% by weight of 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid, water, from 0.005% to 10% by weight of gelling agent, from 0.2% to 50% by weight of hydrophilic solvent, from 2% to 50% by weight of cosolvent, and optionally, from 0 to 15% by weight of additives. 10. The composition as claimed in claim 1, wherein a maximum amount of the active agent absorbed in the dermis and the epidermis 16 hours after application is from 5 ng/cm.sup.2 to 15 ng/cm.sup.2. 11. The composition as claimed in claim 1, wherein a maximum amount of the active agent absorbed in the epidermis is obtained from 1 to 6 hours after application. 12. The composition as claimed in claim 1, wherein the composition is provided in the form of a medicament. 13. The composition as claimed in claim 5, wherein the polymer of microbiological origin is xanthan gum. 14. The composition as claimed in claim 13, wherein the gelling agent is selected from the group consisting of: acrylate/C10-30 alkyl acrylate crosspolymers, polyacrylamides, polyacrylamide/isoparaffin C13-14/laureth-7 mixtures, carbomers, polysaccharides, aluminum magnesium silicates, acrylic polymers coupled to hydrophobic chains, modified starches, and carrageenans. 15. The composition as claimed in claim 14, wherein the polyacrylamide is a sodium acrylamide/acryloyldimethyl taurate copolymer/isohexadecane/polysorbate 80 mixture. 16. The composition as claimed in claim 14, wherein the polysaccharides are selected from the group consisting of xanthan gum, gellan gum guar gum, and cellulose. 17. The composition of claim 16, wherein the cellulose is selected from the group consisting of microcrystalline cellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and sodium carboxymethylcellulose. 18. The composition as claimed in claim 7, wherein the glycol is selected from the group consisting of propylene glycol, dipropylene glycol, and mixtures thereof. 19. The composition as claimed in claim 8, wherein the one or more preserving agents is selected from the group consisting of methyl paraben, propyl paraben, benzalkonium chloride, phenoxyethanol, benzyl alcohol, potassium sorbate, benzoic acid, 2-bromo-2-nitropropane-1,3-diol, chlorhexidine, chlorocresol, ethyl alcohol and diazolidinylurea. 20. The composition of claim 8, wherein the one or more agents for improving the properties of the formulae on application is cyclomethicone or dimethicone. 21. The composition as claimed in claim 8, wherein the one or more chelating agents is selected from the group consisting of an EDTA (ethylenediaminetetraacetic acid) and salts thereof, dihydroglycerol, citric acid, tartaric acid and gluconolactone. 22. The composition as claimed in claim 8, wherein the one or more antioxidants is selected from the group consisting of vitamin E and vitamin C. 23. The composition as claimed in claim 22, wherein the vitamin E is DL-alpha-tocopherol or tocopheryl acetate. 24. The composition as claimed in claim 22, wherein the vitamin C is ascorbyl palmitate or butylhydroxytoluene. 25. The composition as claimed in claim 8, wherein the one or more soothing agents and/or anti-irritants is selected from the group consisting of PPG-12/SMDI copolymer, glycyrrhetinic acid, hyaluronic acid or its sodium hyaluronate form, and allantoin. 26. Then composition as claimed in claim 9, wherein the amount of the 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid is from 0.0001% to 0.1% by weight. 27. The composition as claimed in claim 26, wherein the amount of the 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid is from 0.001% to 0.1% by weight. 28. The composition as claimed in claim 9, wherein the amount of the gelling agent is from 1% to 4% by weight. 29. The composition as claimed in claim 9, wherein the amount of the hydrophilic solvent is from 0.5% to 30% by weight. 30. The composition as claimed in claim 9, wherein the amount of cosolvent is from 10% to 40% by weight. 31. The composition as claimed in claim 9, wherein the amount of the additives is from 0.1% to 10% by weight. 32. The composition as claimed in claim 1, wherein Y represents a heteroatom selected from oxygen or sulfur. 33. The composition as claimed in claim 14, wherein the acrylic polymer coupled to hydrophobic chains is PEG-150/decyl/SMDI copolymer. 34. The composition as claimed in claim 14, wherein the modified starch is a modified potato starch. 35. The composition as claimed in claim 14, wherein the carrageenan is divided up into four major families: .kappa., .lamda., .beta., .omega.. 36. The composition of claim 5, wherein the cellulose is selected from the group consisting of microcrystalline cellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose and sodium carboxymethylcellulose. 37. A method of treating a pathological condition, the method comprising administering to an individual subject in need thereof an effective amount of the composition as claimed in claim 1, wherein the pathological condition is selected from the group consisting of: common acne, comedonal acne, polymorphic acne, acne rosacea, nodulocystic acne, acne conglobata, senile acne or secondary acne; ichthyosis, ichthyosiform conditions, lamellar ichthyosis, Darier's disease, palmoplantar keratoderma, leukoplakia, pityriasis rubra pilaris and leukoplakiform conditions, cutaneous or mucosal (buccal) lichen; dermatological conditions with an inflammatory immunoallergic component, with or without a cell proliferation disorder; skin disorders caused by exposure to UV radiation, photo-induced or chronological skin aging, actinic keratoses and pigmentations, or pathological conditions associated with chronological or actinic aging; common warts, flat warts, molluscum contagiosum, epidermodysplasia verruciformis, or oral or florid papillomatoses; immune dermatoses; stigmata of epidermal and/or dermal atrophy induced by local or systemic corticosteroids, or any other form of cutaneous atrophy; healing disorders, or for repairing stretch marks, or for promoting healing; conditions of fungal origin at the cutaneous level; pigmentation disorders; and cutaneous or mucosal cancerous or precancerous conditions. 38. The method as claimed in claim 37, wherein the dermatological condition with an inflammatory immunoallergic component is selected from cutaneous, mucosal or ungual psoriasis, psoriatic arthritis, atopic dermatitis and eczema. 39. The method as claimed in claim 37, wherein the pathological condition associated with chronological or actinic aging is selected from xerosis, pigmentations or wrinkles. 40. The method as claimed in claim 37, wherein the immune dermatosis is lupus erythematosus. 41. The method as claimed in claim 37, wherein the collagen disease is scleroderma. 42. The method as claimed in claim 37, wherein the condition of fungal origin at the cutaneous level is tinea pedis or tinea versicolor. 43. The method as claimed in claim 37, wherein the pigmentation is hyperpigmentation, melasma, hypopigmentation or vitiligo. 44. The method as claimed in claim 37, wherein the cutaneous or mucosal cancerous or precancerous condition is selected from the group consisting of tinic keratoses, Bowen's disease, in-situ carcinomas, keratoacanthomas, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous lymphomas. 45. The method as claimed in claim 44, wherein the cutaneous lymphoma is T lymphoma. 46. A method of treating a pathological condition, the method comprising administering to an individual subject in need thereof an effective amount of the composition as claimed in claim 1, wherein the pathological condition is selected from the group consisting of lupus erythematosus, bullous immune diseases, and collagen diseases. 47. The method as claimed in claim 37, wherein the secondary acne is solar acne, acne medicamentosa or occupational acne.