Claims for Patent: 9,084,778

Summary for Patent: 9,084,778

Title:	Topical compositions containing a retinoid of the oil-in-water emulsion type
Abstract:	A composition in the form of an oil in water emulsion, preferably without emulsifier, is described. The composition can include, in a physiologically acceptable environment, at least one new retinoid. Also described, is the method of preparing the composition and its use in cosmetics and dermatology.
Inventor(s):	Duprat; Agnes (Mougins, FR), Mallard; Claire (Mougins, FR)
Assignee:	GALDERMA RESEARCH & DEVELOPMENT (Biot, FR)
Application Number:	13/906,336
Patent Claims:	1. A pharmaceutical composition comprising: an oily phase comprising at least one compound of formula (I) ##STR00009## where: R.sub.1 is a hydrogen atom, an alkyl radical of 1 to 4 carbons or a --CF.sub.3 radical; R.sub.2 is a hydrogen atom, an alkyl or alkoxy radical of 1 to 4 carbon atoms or a chlorine atom; R.sub.3 is a hydrogen atom, a linear or branched alkyl or alkoxy radical of 1 to 10 carbon atoms optionally substituted by a methoxy group; R.sub.4 is a hydrogen atom or an alkyl radical of 1 to 3 carbon atoms; R.sub.5 is a hydrogen atom or an alkyl radical of 1 to 3 carbon atoms; or R.sub.4 and R.sub.5 together form, with the --N--C(.dbd.Y)-- bond, a ring of the pyrrolidine, pyrrolidinone, piperidine or piperidinone ring; Y denotes two hydrogen atoms or a heteroatom; Ar denotes a 1,4-phenyl, 2,5-pyridyl, 5,2-pyridyl or 2,5-thiophenyl ring; X denotes an oxygen atom, optionally substituted by an alkyl or alkylamine chain or a single C--C bond; and A denotes a hydrogen atom or the following formula: ##STR00010## where Q is an oxygen atom or a --NH-- bond; R.sub.6 denotes a hydrogen atom, an alkyl radical of 1 to 6 carbon atoms, a cycloalkyl radical of 3 to 6 carbon atoms, a --C(O)CH.sub.2 or --C(O)CH.sub.2CH.sub.3 radical; R.sub.7 and R.sub.7' denote, independently of each other, a hydrogen atom or a hydroxyl group on condition that R.sub.7 and R.sub.7' are not at the same time a hydroxyl group; and n is equal to 0, 1, 2, 3, 4 or 5; at least a principal solvent of compound of formula(I) and at least a co-solvent oil of compound of formula(I); and an aqueous phase comprising at least a gelifying agent. 2. The composition according to claim 1, wherein the compound of formula (I) is defined so that: R1 is a hydrogen atom, the t-butyl or i-propyl radical; R2 is a hydrogen atom, the t-butyl or i-propyl radical; R3 is a hydrogen atom or the ethyl radical; R4, R5 are independently from each other the methyl or ethyl radical or together form a pyrrolidine ring; and A, as previously defined, where R.sub.6 denotes a hydrogen atom, the i-propyl or t-butyl radical, a cycloalkyl radical of 3 to 6 carbon atoms, a --C(O)CH.sub.2 or --C(O)CH.sub.2CH.sub.3 radical. 3. The composition according to claim 1, wherein the compound is 3''-tert-butyl-4'-(2-hydroxy-ethoxy)-4''-pyrrolidin-1-yl-[1,1';3',1'']-te- rphenyl-4-carboxylic acid. 4. The composition according to claim 1, wherein the composition is devoid of a seperate emulsifying agent. 5. The composition according to claim 1, wherein the gelifying agent is selected from the group consisting of: acrylates/C10-30 alkyl acrylate crosspolymer sold under the name of PEMULEN TR-1 or PEMULEN TR-2, polyacrylamide gelifiers, a mixture polyacrylamide/isoparaffin C13-14/laureth-7 sold under the name of SEPIGEL 305, carbomers sold under the names of ULTREZ 20.RTM., ULTREZ 10.RTM., CARBOPOL 1382.RTM. or CARBOPOL ETD2020NF.RTM., CARBOPOL 981 and CARBOPOL 980, xanthan gum, gellan gum sold under the name of KELCOGEL, guar gum and cellulose polysaccharides, aluminium magnesium silicates, acrylic polymers linked to hydrophobic chains, modified starches their mixtures, and carrageenans. 6. The composition according to claim 1, wherein the principal solvent is selected from the group consisting of benzyl alcohol, laureth-4, phenoxyethanol, propylene glycol monocaprylate, pentylene glycol and dimethyl isosorbide. 7. The composition according to claim 1, wherein the principal solvent is phenoxyethanol. 8. The composition according to claim 1, wherein the co-solvent oil is selected from the group consisting of caprylic/capric triglycerides, sweet almond oil, propylene glycol monocaprylate, propylene glycol laurate, sorbitan sesquioleate, diisopropyl adipate, PPG-15 stearyl ether, and apricot kernel oil PEG-6 ester. 9. The composition according to claim 1, wherein the composition also contains one or more additives selected from the group consisting of: a preservative system selected from the group consisting of methyl parabene, propyl parabene, benzalkonium chloride, phenoxyethanol sold under the name of PHENOXETOL, benzyl alcohol, potassium sorbate, benzoic acid, 2-bromo-2-nitropropane-1,3-diol sold under the name of BRONOPOL, chlorohexidine, chlorohexidine digluconate, chlorocresole, ethyl alcohol and diazolidinyl urea, chelating agents mixtures thereof, antioxidants, and palliatives and anti-irritants. 10. The composition according to claim 1, wherein the composition can also contain a mineral oil. 11. The composition according to claim 1, wherein the composition can also contain a moistening agent. 12. The composition according to claim 1, wherein the composition can also contain a silicone oil. 13. The composition according to claim 1, wherein the composition can also contain ethanol. 14. The composition according to claim 1, wherein the composition comprises thefollowing ingredients: from 0.00001% to 1% w/w of 3''-tert-butyl-4'-(2-hydroxy-ethoxy)-4''-pyrrolidin-1-yl-[1,1':3',1'']-te- rphenyl-4-carboxylic acid from 0.005 to 10% w/w of gelifying agent for the aqueous phase from 0.2 to 5% w/w of solvent from 0.5 to 50% w/w of co-solvent oil from 0 to 20% w/w of mineral oil from 0 to 50% w/w of polyol from 0 to 10% w/w of silicone oil from 0 to 5% w/w of preservative system from 0 to 30% w/w of ethanol from 0 to 15% w/w of additives. 15. The composition according to claim 1, wherein the composition is a water in oil emulsion. 16. The composition according to claim 1, wherein the maximum quantity of compound of formula (I) absorbed in the dermis and epidermis 16 hours after application is between 6 ng/cm.sup.2 and 19 ng/cm.sup.2. 17. The composition according to claim 16, wherein the maximum quantity of compound of formula (I) absorbed in the dermis and epidermis 16 hours after application is between 6.8 ng/cm.sup.2 and 10.6 ng/cm.sup.2. 18. The composition according to claim 1, wherein the maximum quantity of compound of formula (I) absorbed in the epidermis is attained between 3 hours and 10 hours after application. 19. A medicinal product comprising the composition according to claim 1. 20. A method of treating a pathology, the method comprising administering to a subjiect afflicted with the pathology an effective amount of the composition of claim 1, wherein the pathology is selected from the group consisting of: dermatological conditions associated with a keratinization disorder relating to cellular differentiation and proliferation selected from the group consisting of common acnes. comedonic acnes, polymorphic acnes, rosaceas, nodulocystic acnes, congiobata, senile acnes and secondary acnes; keritinization disorders selected from the group consisting of ichtyoses, ichtyosiform conditions, lamellar ichtyosis, Darner's disease, palmoplantar keratodermias, leukoplasias, pityriasis rubra pilaris and leukoplasiform conditions, cutaneous lichen and mucous (oral) lichen; dermatological disorders with an inflammatory immune-allergic component, with or without cellular proliferation disorder, selected from the group consisting of cutaneous psoriasis, mucous psoriasis and ungueal psoriasis, psoriasic rheumatic dermatitis, atopical dermatitis and eczema; cutaneous disorders due to exposure to UV radiation, photo-induced and chronological ageing of the skin, and to reduce pigmentations and actinic keratoses, and pathologies associated with chronological or actinic ageing, selected from the group consisting of xerosis, pigmentations and wrinkles; a condition associated with benign dermal or epidermal proliferations, whether or not of viral origin, selected from the group consisting of common warts, flat warts, molluscurn contagiosum and verruciform epidermodysplasia, and oral and florid papillomatoses; dermatological conditions optionally including immune dermatoses selected from the group consisting of erythematous lupus, and bullous immune diseases and sclerodermia; stigmata of epidermal and dermal atrophy induced by local and systemic corticosteroids, and any other form of cutaneous atrophy; scarring complaints, to treat and repair stretch marks, and to promote scarring; a disorder of fungal origin in the cutaneous region, selected from the group consisting of tinea pedis and tinea versicolor; pigmentation disorders selected from the group consisting of hyperpigmentation, melasma, hypopigmentation and vitiligo; and cancerous and pre-cancerouscutaneous and mucous conditions selected from the group consisting of actinic keratoses, Bowen's disease, carcinomas in-situ, keratocanthoma and skin cancers selected from the group consisting of basocellular carcinoma (BCC), spinocellular carcinoma (SCC) and T lymphoma. 21. The composition of claim 1, wherein when Y is a heteroatom, the heteroatom is oxygen or sulphur. 22. The composition of claim 5. wherein the gelifying agent is a sodium acrylamide/acryloyidimethyltaurate/isohexadecane/polysoricate 80 sold under the name of SIMULGEL 600 PHA. 23. The composition of claim 5, wherein the xanthan gum is XANTURAL 180.RTM.. 24. The composition of claim 5, wherein the cellulose is selected from the group consisting of a mixture of microcrystalline cellulose and sodium carboxymethylcellulose sold under the name AVICEL CL-611, hydroxypropylmethylcellulose, hydroxyethylcellulose and sodium carboxymethylcellulose. 25. The composition of claim 5, wherein the aluminium magnesium silicate is VEEGUM K. 26. The composition of claim 5, wherein the acrylic polymer is PEG-150/decyl alcohol/SMDI copolymer sold under the name ACULYN 44. 27. The composition of claim 5, wherein the modified starch is a modified potato starch sold under the name STRUCTURE SOLANCE. 28. The composition of claim 5, wherein the carrageenan is selected from the group consisting of the four major families: .kappa., .lamda., .beta., and .omega.. 29. The composition of claim 9, wherein the chelating agent is selected from thr group consisting of EDTA (ethylene diamine tetraacetric acid) and its salts, dihydroglycerine, citric acid, tartaric acid, gluconolactone sold under the name D-(+)-glucono-delta-lactone mixtures thereof. 30. The composition of claim 9, wherein the antioxidant is vitamin E. 31. The composition of claim 30, wherein the vitamin E is DL alpha tocopherol or tocopherol acetate. 32. The composition of claim 9, wherein the antioxidant is vitamin C. 33. The composition of claim 32, wherein the vitamin C is ascorbyl palmitate or butylhydroxy toluene. 34. The composition of claim 9, wherein the palliative or anti-irrant is PPG-12/SMDI copolymer under the name POLYOLPREPOLYMER-2, glycyrrhetinic acid, hyaluronic acid, sodium hyaluronate or an allantoin sold under the name RONACARE ALLANTOINE. 35. The composition of claim 14, wherein the composition comprises from 0.0001% to 0.1% w/w of 3''-tert-butyl-4'-(2-hydroxy-ethoxy)-4''-pyrrolidin-1-yl-[1,1':3',1'']-te- rphenyl-4-carhoxylic acid. 36. The composition of claim 14, wherein the composition comprises from 0.001% to 0.1% w/w of 3'-tert-butyl-4''-(2-hydroxy -ethoxy)-4''-pyrrolidin-1-yl-[1,1':3',1'']-terphenyl-4-carboxylic acid. 37. The composition of claim 14, wherein the composition comprises from 1% to 5% w/w of gelifying agent for the aqueous phase. 38. The composition of claim 14, wherein the composition comprises from 0.5% to 2% w/w of principal solvent. 39. The composition of claim 14, wherein the composition comprises from 4% to 30% w/w of co-solvent oil. 40. The composition of claim 14, wherein the composition comprises from 0% to 5% w/w of mineral oil. 41. The composition of claim 14, wherein the composition comprises from 5% to 35% w/w of polyol. 42. The composition of claim 14, wherein the composition comprises 0% to 4% w/w of silicone oil. 43. The composition of claim 14, wherein the composition comprises from 0.01% to 2% w/w of preservative system. 44. The composition of claim 14, wherein the composition comprises from 0% to 10% w/w of ethanol. 45. The composition of claim 14, wherein the composition comprises from 0.1% to 10% w/w of additives. 46. The composition according to claim 3, wherein the gelifying agent is selected from the group consisting of: acrylates/C10-30 alkyl acrylate crosspolymers sold under the name of PEMULEN TR-1 or PEMULEN TR-2, polyacrylamide gelifiers, a mixture polyacrylamide/isoparaffin C13-14/laureth-7 sold under the name of SEPIGEL 305, carbomers sold under the names of ULTREZ 20.RTM., ULTREZ 10.RTM., CARBOPOL 1382.RTM. or CARBOPOL ETD2020NF.RTM., CARBOPOL 981 and CARBOPOL 980, xanthan gum, gellan gum sold under the name of KELCOGEL, guar gum and cellulose polysaccharides, aluminum magnesium silicates, acrylic polymers linked to hydrophobic chains, modified starches and their mixtures, and carrageenans. 47. The composition according to claim 3, wherein the principal solvent is selected from the group consisting of benzyl alcohol, laureth-4, phenoxyethanol, propylene glycol monocaprylate, pentylene glycol and dimethyl isosorbide. 48. The composition according to claim 3, wherein the principal solvent is phenoxyethanol. 49. The composition according to claim 3, wherein the co-solvent oil is selected from the group consisting of caprylicicapric triglycerides, sweet almond oil, propylene glycol monocaprylate, propylene glycol laurate, sorbitan sesquioleate, diisopropyl adipate, PPG-15 stearyl ether, and apricot kernel oil PEG-6 ester. 50. The composition according to claim 3, wherein the composition also contains one or more additives selected from the group consisting of: a preservative system selected from the group consisting of methyl parabene, propyl parabene, benzalkoniurn chloride, phenoxyethanol sold under the name of PHENOXETOL, benzyl alcohol, potassium sorbate, benzoic acid, 2-bromo-2-nitropropane-1,3-diol sold under the name of BRONOPOL, chlorhexidine, chlorhexidine digluconate, chlorocresole, ethyl alcohol and diazolidinyl urea, chelating agents and mixtures thereof, antioxidants, and palliatives and anti-irritants. 51. The composition according to claim 3, wherein the composition can contain a mineral oil. 52. The composition according to claim 3, wherein the composition can also contain a moistening agent. 53. The composition according to claim 3, wherein the composition can also contain a silicone oil. 54. The composition according to claim 3, wherein the composition can also contain ethanol. 55. The composition according to claim 3, wherein the composition is a water in oil emulsion. 56. The composition according to claim 3, wherein the maximum quantity of said compound absorbed in the dermis and epidermis 16 hours after application is between 6.8 ng/cm.sup.2 and 19 ng/cm.sup.2. 57. The composition according to claim 3, wherein the maximum quantity of said compound absorbed in the dermis and epidermis 16 hours after application is between 6.8 ng/cm.sup.2 and 10.6 ng/cm.sup.2. 58. The composition according to claim 3, wherein the maximum quantity of said compound absorbed in the epidermis is attained between 3 hours and 10 hours after application. 59. A medicinal product comprising the composition according to claim 3. 60. A method of treating a pathology, the method comprising treating a subject afflicted with the pathology with an effective amount of the composition according to claim 3, wherein the pathology is selected from the group consisting of: dermatological conditions associated with a keratinization disorder relating to cellular differentiation and proliferation selected from the group consisting of common ernes, comedonic acnes, polymorphic acnes, rosaceas, nodulocystic acnes, conglobata, senile acnes and secondary acnes; keritinization disorders selected from the group consisting of ichtyoses, ichtyosiform conditions, lamellar ichtyosis, Darner's disease, palmoplantar keratodermias, leukoplasias, pityriasis rubra pilaris and leukoplasiform conditions, cutaneous lichen and mucous (oral) lichen; dermatological disorders with an inflammatory immune-allergic component, with or without cellular proliferation disorder, selected from the group consisting of cutaneous psoriasis, mucous psoriasis and ungueal psoriasis, psoriasic rheumatic dermatitis, atopical dermatitis and eczema; cutaneous disorders due to exposure to UV radiation, photo-induced and chronological ageing of the skin, and to reduce pigmentations and actinic keratoses, and pathologies associated with chronological or actinic ageing, selected from the group consisting of xerosis, pigmentations and wrinkles; a condition associated with benign dermal or epidermal proliferations, whether or not of viral origin, selected from the group consisting of common warts, flat warts, molluscum contagiosum and verruciform epidermodysplasia, and oral and florid papillomatoses; dermatological conditions optionally including immune dermatoses selected from the group consisting of erythematous lupus, and bullous immune diseases and sclerodermia; stigmata of epidermal and dermal atrophy induced by local and systemic corticosteroids, and any other form of cutaneous atrophy; scarring complaints, to treat and repair stretch marks, and to promote scarring; a disorder of fungal origin in the cutaneous region, selected from the group consisting of tinea pedis and tinea versicolor; pigmentation disorders selected from the group consisting of hyperpigmentation, melasma, hypopigmentation and vitiligo; and cancerous and pre-cancerous cutaneous and mucous conditions selected from the group consisting of actinic keratoses, Bowen's disease, carcinomas in-situ, keratocanthoma and skin cancers selected from the group consisting of basocellular carcinoma (BCC), spinocellular carcinoma (SCC) and T lymphoma. 61. The composition according to claim 46, wherein the gelifying agent is a sodium acrylamidetacryloyldimethyltaurate/isohexadecaneipolysorbate 80 sold under the name of SIMULGEL 600 PHA. 62. The composition according to claim 46, wherein the xanthan gum us XANTURAL 180.RTM.. 63. The composition according to claim 46, wherein the cellulose is selected from the group consisting of a mixture of microcrystalline cellulose and sodium carboxymethylcellulose sold under the name AVICEL CL-611, hydroxypropylmethylcellulose, hydroxyethylcellulose and sodium carboxymethylcellulose. 64. The composition according to claim 46, wherein the aluminum magnesium silicate is VEEGUM K. 65. The composition according to claim 46, wherein the acrylic polymer is PEG-150/decyl alcohol/SMDI copolymer sold under the name ACULYN 44. 66. The composition according to claim 46, wherein the modified starch is a modified potato starch sold under the name STRUCTURE SOLANCE. 67. The composition according to claim 46, wherein the carrageenan is selected from the group consisting of the four major families: .kappa., .lamda., .beta., and .omega.. 68. The composition according to claim 50, wherein the chelating agent is selected from the group consisting of EDTA (ethylene diamine tetraacetric acid) and its salts, dihydroglycerine, citric add, tartaric add, gluconolactone sold under the name D-(+)-glucono-delta-lactone and mixtures thereof. 69. The composition according to claim 50, wherein the antioxidant is vitamin E. 70. The composition according to claim 69, wherein the vitamin E is DL alpha tocopherol or tocopherol acitate. 71. The composition according to claim 50, wherein the antioxidant is vitamin C. 72. The composition according to claim 71, wherein the vitamin Cis ascorbyl palmitate or butylhydroxytoluene. 73. The composition according to claim 50, wherein the palliative or anti-irritant is PPG-12/SMDI copolymer under the name POLYOLPREPOLYMER-2, glycyrrhetinic add, hyaluronic add, sodium hyaluronate or an allantoin sold under the name of RONACARE ALLANTOINE.