Use of salicylic acid for regulating skin wrinkles and/or skin atrophy

Abstract: The present invention relates to the use of a cosmetic composition comprising a safe and effective amount of a sunscreening agent and a safe and effective amount of salicylic acid for regulating wrinkles and/or atrophy in mammalian skin.

Description: Technical Field The present invention relates to the field of anti-aging of skin Specifically, the invention relates to use of cosmetic compositons excluding methods of treatment of the human or animal body by surgery or therapy and diagnostic methods for effacing and preventing wrinkles and/or atrophy in mammalian skin. Background of the Invention Skin is subject to abuse by many extrinsic (environmental) factors as well as intrinsic (chronoaging) factors. A common extrinsic factor is exposure to ultraviolet radiation. Whether extrinsic or intrinsic, the abuse results in wrinkling of the skin. To many people, skin wrinkles are a reminder of the disappearance of youth. As a result, the elimination of wrinkles has become a booming business in youth-conscious societies. Treatments range from cosmetic creams and moisturizers to various forms of cosmetic surgery. Chronoaging results in the thinning and general degradation of skin. As the skin naturally ages, there is a reduction in the cells and blood vessels that supply the skin. There is also a flattening of the dermal-epidermal junction which results in weaker mechanical resistance of this junction. As a consequence, older persons are more susceptive to blister formation in cases of mechanical trauma or disease processes. (See Oikarinen, (1990) "The Aging of Skin: Chronoaging Versus Photoaging", Photodermatal. Photoimmunol. Photomed ., Vol. 7, pp 3-4). It is known to use salicyclic acid for the treatment of acne, see for example, U.S Patents 4,891,227 and 4,891,228, to Thaman et al., both issued January 2, 1990. Further, salacyclic acid has been used for the removal of wart, corns and calluses; for the treatment of psoriasis, seborrheic dermatitis and dandruff; and for the topical treatment of ringworm infection. A listing of commercially available products containing salicylic acid will be found in the Physician's Desk Reference, 45th Edition, 1991, page 323. However, these prior art uses of saliciylic acid have generally involved short term treatments in which relatively large doses of the acid are applied (i.e., sufficient to cause significant irritation and often peeling) in order to obtain a cure or treatment of the particular condition, such as removal of comedones, as opposed to persistent treatment of normal aging skin. Object of the Present Invention It is object of the present invention to provide use of a cosmetic composition comprising a safe and effective amount of salicylic acid(*) for regulating wrinkles and/or atrophy in mammalian skin, excluding methods of treatment of the human or animal body by surgery or therapy and diagnostic methods. All percentages and ratios used herein are by weight and all measurements are at 25°C unless otherwise indicated. Detailed Description of the Invention As used herein, "alkyl" means an unsubstituted carbon-containing chain which may be straight, branched or cyclic, preferably straight or branched, more preferably straight; saturated, monoun-saturated (i.e., one double or triple bond in the chain), or polyunsaturated (i.e., two or more double bonds in the chain; two or more triple bonds in the chain; one or more double and one or more triple bonds in the chain), preferably saturated. As used herein, "topical application" means directly laying on or spreading on outer skin. As used herein, "pharmaceutically-acceptable" means that drugs, medicaments or inert ingredients which the term describes are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, incompatibility, instability, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio. As used herein, "regulating wrinkles" means preventing, retarding, arresting, or reversing the process of wrinkle formation in mammalian skin. As used herein, "skin atrophy" means the thinning and/or general degradation of the dermis often characterized by a decrease in collagen and/or elastin as well as decreased number, size and doubling potential of fibroblast cells. Skin atrophy is a natural result of aging. Skin atrophy is often an undesirable side effect resulting from treatment with corticosteroids. As used herein, "regulating skin atrophy" means preventing, retarding, arresting, or reversing the process of atrophy in mammalian skin. As used herein, "safe and effective amount" means an amount of compound or composition sufficient to significantly induce a positive modification in the condition to be treated, but low enough to avoid serious side effects (at a reasonable benefit/risk ratio), within the scope of sound medical judgment. The safe and effective amount of the compound or composition will vary with the particular condition being treated, the age and physical condition of the patient being treated, the severity of the condition, the duration of the treatment, the nature of concurrent therapy, the specific compound or composition employed, the particular pharmaceutically-acceptable carrier utilized, and like factors within the knowledge and expertise of the attending physician. As used herein, "chronic treatment" means continued treatment with an active agent over an extended period during a subject's lifetime, preferably for at least about three weeks, more preferably from about three months to about twenty years, more preferably from about six months to about ten years, more preferably still from about one year to about five years. As used herein, all percentages are by weight unless otherwise specified. Active Compound The present invention relates to the use of a cosmetic composition comprising a safe and effective amount of salicylic acid and a safe and effective amount of a sunscreening agent for regulating wrinkes and/or atrophy to mammalian skin excluding methods of treatment of the human or animal body by surgery or therapy and(*) . Most preferred is salicylic acid in a hydroalcoholic solution. Salicylic acid is a well known active component and is generally described in U.S. Patent 4,514,385, to Damani, et al., assigned to Alcon Laboratories, issued April 30, 1985. EP-A-0 378 936 discloses the use of a cosmetic composition comprising a salicylic acid derivative against skin aging. US-A-4 608 370 discloses a method for treating the face to impart a youthful and healthy complexion, which comprises applying to said face a composition comprising salicylic acid, resorcinol, lactic acid and ethyl alcohol. The preferred topical carrier comprises a hydroalcoholic solution at pH 2 to 4 of salicylic acid as the active anti-acne ingredient together with a specific anionic surfactant component. More preferably such active is a stable, hydroalcoholic composition having a pH value of from 2 to 4 and containing from about 0.2 to about 5.0 percent by weight of salicylic acid and from about 0.2 to about 5.0 percent by weight of sodium methyl cocoyl taurate and/or sodium methyl oleoyl taurate as the anionic surfactant component. Generally, a sufficient amount of a cosmetically acceptable alkaline component (i.e., alkalizing agent) to provide and maintain the composition with a pH from about 2.0 to about 4 is included. As the alcohol component of the hydroalcoholic solvent, from about 10 to about 60 percent by weight of ethyl alcohol, measured as total C 2 H 5 OH content, is preferred although a like amount of isopropyl alcohol (C 3 H 7 OH) may also be beneficially utilized. From about 30 to about 80 percent by weight of water is also required as the aqueous component of the hydroalcoholic solvent. The anionic surfactant component of this active composition, i.e., the taurate surfactant component, is specifically directed to sodium methyl cocoyl taurate and sodium methyl oleoyl taurate, both of which are readily available from diverse commercial suppliers, as noted in The Cosmetic, Toiletry and Fragrance Association (CTFA) Cosmetic Ingredient Dictionary, 3rd Edition, 1982, pages 286-287. Although it is preferred to use the taurate surfactant as the sole surfactant in the active compositions, other surfactants may be included, the nonionic type having preference over the anionic type in view of the relative non-irritating characteristic to the skin of the former. Cationic type surfactants, which are most irritating to the skin, are less preferred because of their marked susceptibility to hydrolysis at the low acidic pH of the subject compositions. The pH value of the preferred active component, from about 2 to about 3.5, may be achieved by use of appropriate cosmetically acceptable primary or dual buffer systems. In most instances, the resultant pH of the hydroalcoholic solution of salicylic acid is slightly below or at the lower end of the indicated range, and all that is required to adjust the pH to a desired higher value within the indicated range is to add an alkaline additive such as is commonly utilized in cosmetic formulations for such purpose. Although sodium carbonate is preferred, other suitable alkalizing agents include potassium carbonate, sodium hydroxide, potassium hydroxide and triethanolamine. If deemed necessary to change or adjust the pH to a lower value, a suitable cosmetically acceptable acidifying agent such as citric acid may be employed. The composition according to the present invention may further comprise a pharmaceutically acceptable carrier. Optimum regulation of skin wrinkling resulting from exposure to U.V. light is obtained by using a combination of the salicylic acid active of the present invention together with sunscreens. Photodamage is a predominant cause of skin wrinkling. Thus, for purposes of wrinkle prevention, the combination of the active compound with a UVA and/or UVB sunscreen is most desirable. The inclusion of sunscreens in compositions of the present invention provide immediate protection against acute UV damage. Thus, the sunscreen prevents further wrinkle formation caused by UV radiation, while the active compound regulates existing wrinkles and skin atrophy. A wide variety of conventional sunscreening agents are suitable for use in combination with the active compound. Segarin, et al., at Chapter VIII, pages 189 et seq., of Cosmetics Science and Technology, disclose numerous suitable agents. Specific suitable sunscreening agents include, for example: p-aminobenzoic acid, its salts and its derivatives (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid); anthranilates (i.e., o-aminobenzoates; methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters); salicylates (amyl, phenyl, benzyl, menthyl, glyceryl, and dipropyleneglycol esters); cinnamic acid derivatives (methyl and benzyl esters, α-phenyl cinnamonitrile; butyl cinnamoyl pyruvate); Dihydroxycinnamic acid derivatives (umbelliferone, methylumbelliferone, methylaceto-umbelliferone); trihydroxycinnamic acid derivatives (esculetin, methylesculetin, daphnetin, and the glucosides, esculin and daphnin); hydrocarbons (diphenylbutadiene, stilbene); dibenzalacetone and benzalacetophenone; Naphtholsulfonates (sodium salts of 2-naphthol-3,6-disulfonic and of 2-naphthol-6,8-disulfonic acids); Dihydroxy-naphthoic acid and its salts; o- and p-Hydroxybiphenyldisulfonates; Coumarin derivatives (7-hydroxy, 7-methyl, 3-phenyl); Diazoles (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl naphthoxazole, various aryl benzothiazoles); Quinine salts (bisulfate, sulfate, chloride, oleate, and tannate); Quinoline derivatives (8-hydroxyquinoline salts, 2-phenylquinoline); Hydroxy- or methoxy-substituted benzophenones; Uric and vilouric acids; Tannic acid and its derivatives (e.g., hexaethylether); (Butyl carbotol) (6-propyl piperonyl) ether; Hydroquinone; Benzophenones (Oxybenzene, Sulisobenzone, Dioxybenzone, Benzoresorcinol, 2,2',4,4'-Tetrahydroxybenzophenone, 2,2'-Dihydroxy-4,4'-dimethoxybenzophenone, Octabenzone; 4-Isopropyldibenzoylmethane; Butylmethoxydibenzoylmethane; Etocrylene; and 4-isopropyl-di-benzoylmethane. Preferred sunscreens useful in the compositions of the present invention are 2-ethylhexyl-p-methoxycinnamate, butyl-methoxydibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyl-dimethyl-p-aminobenzoic acid and mixtures thereof. A safe and effective amount of sunscreen is used in the compositions of the present invention. The sunscreening agent must be compatible with the active compound. Generally the composition comprises from 1% to 20%, preferably from 2% to 10%, of a sunscreening agent. Exact amounts will vary depending upon the sunscreen chosen and the desired Sun Protection Factor (SPF). Also particularly useful in the present invention are sunscreens such as those disclosed in Sabatelli, U.S. Patent Application Serial No. 054,085 (filed June 2, 1987) and Sabatelli et al., U.S. Patent Application Serial No 054,046 (filed June 2, 1987). The sunscreening agents disclosed therein have, in a single molecule, two distinct chromophore moieties which exhibit different ultra-violet radiation absorption spectra. One of the chromophore moieties absorbs predominantly in the UVB radiation range and the other absorbs strongly in the UVA radiation range. An agent may also be added to any of the compositions of the present invention to improve the skin substantivity of those compositions, particularly to enhance their resistance to being washed off by water, or rubbed off. A preferred agent which will provide this benefit is a copolymer of ethylene and acrylic acid. Compositions comprising this copolymer are disclosed in U.S. Patent 4,663,157, Brock, issued May 5, 1987. The composition for topical application will comprise from about 0.01% to about 50%, preferably from about 0.1% to about 20%, more preferably from about 1% to about 5% of salicylic acid. By "chronic" application, it is meant herein that the period of topical application may be over the lifetime of the subject, preferably for a period of at least about three weeks, more preferably from about three months to about twenty years, more preferably from about six months to about ten years, more preferably still from about one year to about five years, thereby resulting in regulation of wrinkles and/or atrophy in mammalian skin. The following examples do not form part of the present invention but are useful for its understanding. EXAMPLE I A pad of the present invention is made as follows: Pad Composition Weight % Substrate A Cellulose-based nonwoven 100.0 Substrate B Polyester (denier = 6) 45.0 Orion (denier = 8) 15.0 Styrene-butadiene resin 40.0 Laminate Polyethylene Powder Melt 100.0 Active Composition Weight % Salicylic acid 2.0 Na Methyl cocoyl taurate 3.0 C 2 H 5 OH (95% ethanol) 35.0 Witch Hazel distillate 5.0 Quaternium-22 1.0 Menthol 0.1 Aloe Vera Gel 0.5 Fragrance 0.05 Water q.s. Substrate A has a basis weight of about 55 grams per square yard and a loft of about 35 mills. Substrate B has a basis weight of about 65 grams per square yard and a loft of about 70 to 80 mills. The two materials are laminated together by applying a thin coat of Polyethylene power to Substrate A and heating with IR lamps. Substrate A and B are then joined at a hip roll to compress and bond the materials. The resulting nonwoven fabric has a loft of about 90 to 100 mills. The resulting material is then cut into an oval shape (5 cm. x 7 cm.). The active components are combined to form a solution and the pad composition is saturated in this solution. This composition is useful for topical application to regulate skin wrinkles and/or skin atrophy. Use of an amount of the composition to deposit about 2 mg/cm 2 of the active compound to the skin is appropriate. EXAMPLE II A pad of the present invention is made by combining the following components as in Example I: Pad Composition Weight % Substrate A Cellulose-based nonwoven 100.0 Substrate B Polyester (denier = 6) 45.0 Orlon (denier = 8) 15.0 Styrene-butadiene resin 40.0 Laminate Polyethylene Powder Melt 100.0 Active Composition Weight % Salicylic acid 2.0 C 2 H 5 OH (95% ethanol) 35.0 Glycerin 2.0 Aloe Vera Gel 1.0 Menthol 0.05 Triethanol Amine 0.7 Fragrance 0.15 Water q.s. This composition is useful for topical application to regulate skin wrinkles and/or skin atrophy. Use of an amount of the composition to deposit about 2 mg/cm 2 of the active compound to the skin is appropriate. EXAMPLE III A topical composition is prepared by combining the following components utilizing conventional mixing techniques. Active Composition Weight % Salicylic acid 1.25 Ascorbic acid 5.00 Na Methyl cocoyl taurate 1.5 C 2 H 5 OH (95% ethanol) 45.0 Witch Hazel distillate 5.0 Quaternium-22 1.0 Menthol 0.05 Fragrance 0.05 Water 41.15 This composition is useful for topical application to regulate skin wrinkles and/or skin atrophy. Use of an amount of the composition to deposit about 2 mg/cm 2 of the active compound to the skin is appropriate. EXAMPLE IV A topical composition is made by combining the following components using conventional mixing technology. Ingredient W/W% Water, Purified 54.0 Alcohol SD 40 40.0 Polyacrylamide and C 13-14 Isoparaffin and Laureth-7 4.0 Salicylic Acid 2.0 Water is added to a suitable size container. While mixing at a moderate speed (300 rpm), the polyacrylamide isoparaffin and laureth-7 is added to the water. Separately, the alcohol is placed in a container and covered. Using a Lightnin' Mixer with a 3 blade paddle prop, the salicylic acid is added to the alcohol and mixed at a low speed (100 rpm) until all salicylic acid is dissolved. The alcohol is slowly added to the water phase to form a gel. The resulting gel is mixed at moderate speed until uniform. This composition is useful for topical application to regulate skin wrinkles and/or skin atrophy. Use of an amount of the composition to deposit about 2 mg/cm 2 of the active compound to the skin is appropriate. EXAMPLE V A topical composition is made by combining the following components using conventional mixing technology as in Example IV. Ingredient W/W% Water q.s. Alcohol SD 40 40.0 Salcare SC92 3.0 Salicylic Acid 2.0 Menthol 0.05 N 92 EDTA 0.05 Glycerin 2.00 This composition is useful for topical application to regulate skin wrinkles and/or skin atrophy. Use of an amount of the composition to deposit about 2 mg/cm 2 of the active compound to the skin is appropriate.

Claims: Use of a cosmetic composition comprising a safe and effective amount of a sunscreening agent and a safe and effective amount of salicylic acid for regulating wrinkles and/or atrophy in mammalian skin excluding methods of treatment of the human or animal body by surgery or therapy and diagnostic methods. Use according to Claim 1 wherein the composition comprises from 0.01% to 50% of salicylic acid. Use according to Claim 1 wherein the composition comprises from 0.1% to 20% of salicylic acid. Use according to Claim 1 wherein the composition comprises from 1% to 5% of salicylic acid. Use according to any of Claims 1 to 4 wherein the composition comprises from 1% to 20% of a sunscreening agent. Use according to any of Claims 1 to 4 wherein the composition comprises from 2% to 10% of a sunscreening agent. Use according to any of Claims 1 to 6 wherein the sunscreening agent is selected from 2-ethylhexyl-p-methoxycinnamate, butyl-methoxydibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyl-dimethyl-p-aminobenzoic acid, and mixtures thereof. Use according to any of Claims 1 to 7 wherein the composition further comprises a pharmaceutically acceptable carrier.

Inventors: BLANK ROY LONNIE, BLANK, ROY LONNIE
Applicants: RICHARDSON VICKS INC, RICHARDSON-VICKS INC.
Application year: 1992
Main classification: A61K7
IPC codes: A61K8, A61Q19