MXPA96003878A - Methods for using polyolpolianionic derivatives cycles to regulate wrinkles in the p - Google Patents

Abstract

The present invention involves methods for the regulation of wrinkles in the skin and / or atrophy in the skin of a mammal comprising topically applying to the skin of a mammal in need of treatment, a composition comprising a safe and effective amount of a derivative of cyclic polyanionic polyol having the structure: formula (I) wherein n is an integer from 1 to 3 and each X is, independently, selected from the group consisting of OSO3-, OPO3-, SO3-, PO3-, Co2-, and OH. At least three X's are different from OH. The compositions also contain an appropriate amount of pharmaceutically acceptable cations to balance the charge on the poly derivatives.

Description

METHODS FOR USING POLYOLIONIC CYLINIC POLYOLATE DERIVATIVES FOR REGULAR WRINKLES IN THE SKIN.

TECHNICAL FIELD The present invention relates to the field of skin aging treatment. Specifically, the invention relates to novel methods for using certain compounds to erase, reduce and / or prevent wrinkles in the skin of mammals.

BACKGROUND OF THE INVENTION The skin is subject to abuse by many extrinsic (environmental) factors, as well as intrinsic factors (aging). A common extrinsic factor is exposure to ultraviolet radiation. Whether extrinsic or intrinsic, the abuse results in wrinkling of the skin. For many people, wrinkles on the skin are a reminder of the disappearance of youth. As a result, wrinkle reduction has become a booming business in youth conscious societies. The treatments vary from cosmetic creams and moisturizers to various forms of cosmetic surgery.

Chronological aging results in thinning and general degradation of the skin. As the skin ages naturally, there is a reduction in the cells and blood vessels that supply the skin. There is also a descent of the epidermal-dermal junction that results in mechanical weaknesses in this joint. As a consequence, older people are more susceptible to the formation of ampules in cases of mechanical trauma or disease processes. (See Oi arinen, The Aging of SJin: Chronoaging Versus Photoaging, Photodermatol, Photoi munol, Photomed., Vol. 7, pp 3-4 (1990). It is an object of the present invention to provide methods for regulating wrinkles in the skin and / or atrophy in the skin of the mammal. It is further an object of the present invention to provide topical compositions for the regulation of wrinkles in the skin of a mammal.

BRIEF DESCRIPTION OF THE INVENTION The present invention involves methods for the regulation of wrinkles in the skin and / or atrophy in the skin of a mammal comprising topically applying to the skin of a mammal in need of treatment, a composition comprising a safe and effective amount of a derivative of cyclic polyanionic polyol having the structure: where n is an integer from 1 to 3 and each X is, independently, selected from the group consisting of 0S03-, 0P03-, S03-, P03-, C02-, and OH. At least three X's are different from OH. The compositions also contain an appropriate amount of pharmaceutically acceptable cations to balance the charge on the polyol derivatives. Examples of such cations include (but are not limited to) H +, Na +, K +, Ca ++, Mg ++, Al2 (OH) 5+, NH4 +, (HOCH2CH2) 3NH +, (CH3CH2) 3NH +, HOCH2 (CH3) 2CNH3 +, (HOCH2) 3CNH3 +, CH3 (HOCH2) 2CNH3 +, CH3CH2 (HOCH2) 2CNH3 +, (CH3CH2) 4N, C16HJ3 (CHj) 3N + and (NC16H33) C5H4N + and mixtures thereof.

DETAILED DESCRIPTION OF THE INVENTION As used herein, topical application directly means putting on or spreading on the outer skin. As used herein, "pharmaceutically acceptable" means that inert salts, drugs, medications or ingredients, which describe the term, 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, in proportion to a reasonable benefit / risk ratio. 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 ratio). risk), within the scope of 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 the therapy, the specific compound or composition employed, the pharmaceutically acceptable, particular, used vehicle, and similar factors within the knowledge and experience of the attending physician. As used herein, anti-wrinkle agent means a cyclic polyanionic polyol derivative, or a pharmaceutically acceptable salt thereof, as defined herein above. As used herein, wrinkle regulation means preventing, delaying, erasing, or reversing the wrinkle formation process or decreasing the appearance and / or size of wrinkles in the skin of the mammal. Other manifestations frequently associated with the regulation of wrinkles are a smoother feel and / or improved skin texture. As used herein, regulation of atrophy means preventing, retarding, erasing, or reversing the process of atrophy in the skin of the mammal. As used herein, all percentages are by weight, unless otherwise specified.

ACTIVE AGENT The present invention involves a method for regulating wrinkles and / or atrophies in the skin of the mammal by the topical application of a safe and effective amount of a cyclic polyanionic polyol derivative having the structure: CH - f x-o (you where n is 1, 2 or 3 and each X is, independently, selected from the group consisting of OS03-, OP032", S03-, P03z", C02-, and OH. At least three X are different from OH, preferably at least four X, more preferably at least five, most preferably six. When n is 1 or 2, all X are preferably different from OH. All X's that are different from OH are the same. The active agent is neutralized by an appropriate amount of a pharmaceutically acceptable cation to balance the charge. The cation is selected from a group that includes (but is not limited to) H +, Na +, K +, Ca ++, Mg ++, Al2 (OH) 5+, NH4 +, (HOCH2CH2) 3NH +, (CH3CH2) 3NH +, HOCH2 (CH3) 2CNH3 +, (HOCH2) 3CNH3 +, CH3 (HOCH2) 2CNH3 +, CH3CH2 (HOCH2) 2CNH3 +, (CH3CH2) 4N, C16H33 (CH3) 3N + and (NC16H33) C5H4N + and mixtures thereof. It is preferred that n is 1; more preferred n is 2. It is preferred that X is OS03- or OP032", more preferred OP032". All X's that are not OH are preferably the same. Preferred cations are H +, Na +, K +, NH4 +, (HOCH2CH2) 3NH +, HOCH2 (CH3) 2CNH3 +, (HOCH2) 3CNH3 +, CH3 (HOCH2) 2CNH3 +, or mixtures thereof; more preferred are H +, Na +, NH4 +, HOCH2 (CH3) 2CNH3 +, (HOCH2) 3CNH3 +, CH3 (HOCH2) 2CNH3 +, or mixtures thereof. Preferred active agents of the present invention include: 1,2,3,4,5,6-cyclohexanhexalphosphoric acid (sicolo, myo or other inositol hexakis derived from hexakisphosphoric acid), having the structure: calcium salt of myoinositolhexakisphosphate; tetrapotasic dimagnesium salt of myoinositolhexakisphosphate; potassium magnesium salt of myoinositolhexakisphosphate; dipotassium salt of myoinositolhexakisphosphate; monopotassium salt of myoinositolhexakisphosphate; dodecasodium salt of myoinositolhexakisphosphate; triethanolamine salt of myoinositolhexakisphosphate; ammonium salt of myoinositolhexakisphosphate; cetylpyridine salt of myoinositolhexakisphosphate; cetyltrimethylammonium salt of myoinositolhexakis-phosphate; ammonium salt of myoinositol-l, 3,4, 5,6, pentakis-phosphate; ammonium salt of myoinositol-1,2,5,6-tetrakisphosphate; ammonium salt of myoinositol-1, 3,4,5-tetrakisphosphate-ammonium salt of myo-inositol-1, 3,4,6-tetrakisphosphate; ammonium salt of myoinositol-3,4,5,6-tetrakisphosphate; potassium salt of myoinositol-1,4,5-triphosphate; ammonium salt of myoinositol-1, 3, -triphosphate; ammonium salt of myoinositol-1,5,6-triphosphate; ammonium salt of myo-inositol -2, 4, 5 -triphosphate- 1, 2, 3,4, 5, 6-cyclohexanhexosulfuric acid (simple, myo or other inositol hexakis derived from sulfuric acid), having the structure: Q sodium salt of myo-hexositol hexakissulfate- hexasodium salt of myo-inositol hexakissulfate; myosinitol hexakissulfate potassium salt; 5 Hexapotassium salt of myo-hexositol hexakissulfate; ammonium salt of myo-inositol hexakissulfate; triethanolamine salt of myó-inositol hexakissulfate; myo-inositol hexakissulfate cetylpyridine salt; cetyltrimethylammonium salt of myó-inositol or hexakissulfate; myo-inositol pentakissulfate; myosinitol tetrakissulfate; myo-inonsitol trisulfate; myo-inositol-1,2,3-trisulfate-4,5,6,6-triphosphate. 5 1,2,3,4,5,6-cyclohexane hexaphosphonic acid, having the structure: 1,2,3,4,5,6-cyclohexanhexasulonic acid, having the structure: 1,2,3,4,5,6-cyclohexane hexacarboxylic acid, having the structure: 1,2,3,5, 5- cyclopentanpentasulfuric acid, which has the structure: 1,2,3,4,5-cyclopentanpentalphosphoric acid, having the structure: 1, 2, 3, 4, 5, 6 - cycloheptanheptalsulf uric acid, which has the structure: 1,2,3,4,5,6-cycloheptaheptalphosphoric acid, having the structure: The most preferred active agent includes myo-inositol hexakis phosphoric acid, myo-inositol hexakis sulfuric acid, and myo-inositol-1,2,3-trisulfate-4,5,6-triphosphate. Although the most preferred active agents include io-inositol hexakis phosphoric acid and myó-inositol hexakis sulfuric acid. The most preferred active is the myo-inositol hexakis phosphoric acid. The preferred modes of delivery of the compounds of the present to the skin are passive diffusion and catodal iontophoresis (application of an electric field, either continuous or pulsating, having a polarity such as to propel the anions towards the skin); Passive diffusion is very preferred.

PHARMACEUTICAL COMPOSITIONS The methods of the present invention preferably involve the topical application of a composition to the skin of a mammal, the composition comprising an active anti-wrinkle agent or a mixture of active anti-wrinkle agents as described hereinbefore and a pharmaceutically acceptable topical carrier. The term "pharmaceutically acceptable topical carrier", as used herein, means one or more compatible solid or liquid fillers or encapsulating substances, which are suitable for administration to a human or lower animal. The pharmaceutically acceptable topical carriers should be of sufficiently high purity and sufficiently low toxicity that they are addecuted for topical administration to the human or lower mammal to be treated. A safe and effective amount of the vehicle is preferably from about 50% to about 99.99%, more preferably from about 90% to about 99% of the composition. Variations in the formulation of these vehicles will result in a wide variety of products falling within the scope of the present invention.

TOPICAL COMPOSITIONS The topical compositions useful in this invention can be made in a wide variety of product types. These include, but are not limited to, lotions, creams, beach oils, gels, bars, sprays, ointments, pastes, essences, foams and cosmetic products. These types of products may comprise various types of vehicle systems including, but not limited to, emulsions, gels, dermal and solid proches. The topical compositions useful in this invention formulated as solutions typically include an aqueous or organic, pharmaceutically acceptable solvent. The terms "pharmaceutically acceptable aqueous solvent" and "pharmaceutically acceptable organic solvent" refer to a solvent, which is capable of having dispersed or dissolved therein, the skin lightening agent, and possesses acceptable safety properties (e.g. characteristics of irritation and sensation). Water is a preferred solvent. Examples of suitable organic solvents include: propylene glycol, polyethylene glycol (200-600), polypropylene glycol (425-2025), glycerol, 1,2,4-butanetriol, dimethyl isosorbide, sorbitol esters, 1,2,6-hexanetriol , ethanol, isopropanol, butanediol, dimethyl isosorbide, monoethyl butylene glycol ether and mixtures thereof. These solutions useful in this invention preferably contain from about 0.001% to about 20%, preferably from about 0.01% to about 10%, most preferably from about 0.5% to about 5%, also preferably from about 1% to about 4% of the anti-wrinkle agent, and preferably from about 80% to about 99.99%, most preferably from about 90% to about 99.9% of an acceptable aqueous or organic solvent. The topical compositions of this invention preferably comprise less than 1% by weight of chlorine ions, more preferably less than 0.5%, also preferably less than 0.1%. The composition thereof is preferably free of carbonate ions. The compositions of the present invention preferably comprise 0.1% or more of sulfate ions, more preferably 0.3% or more, also preferably 0.5% or more. The compositions of the present invention comprise 0.1% or more of inorganic phosphate, more preferably 0.3% or more, also most preferably 0.5% or more. The compositions herein preferably comprise 0.1% or more of a combination of sulfate and inorganic phosphate ions, more preferably 0.3% or more, also preferably 0.5% or more.

If the topical compositions useful in the present invention are formulated as an aerosol and applied to the skin as a spray, a propellant is added to the solution composition. Examples of propellants useful herein include, but are not limited to, chlorinated, fluorinated, and chlorofluorinated low molecular weight hydrocarbons. A more complete description of propellants useful herein can be found in Sargain, Cosmeties Science and Technology. 2a. edition, Vol. 2, p. 443-465 (1972). The topical compositions useful in this invention can be formulated as a solution comprising an emollient. An example of a composition formulated in this way could be a product in oil for the beach. Said compositions preferably contain from about 2% to about 50% of a pharmaceutically acceptable topical emollient. As used in the present emollient it refers to materials used for the prevention or relief of dryness, as well as for the protection of the skin. A wide variety of suitable emollients are known, and can be used herein. Sargain, Cosmetics Science and Technology, 2a. edition, Vol. 1, p. 32-43 (1972), incorporated herein by reference, contains numerous examples of suitable materials. A lotion can be formed from a vehicle system in solution. The lotions typically comprise from about 1% to about 20%, preferably from about 5% to about 10% of an emollient; and from about 50% to about 90%, preferably from about 60% to about 80%, of water. Another type of product that can be formulated from a vehicle system in solution, is a cream. A cream typically comprises from about 5% to about 50%, preferably from about 10% to about 20% of an emollient, and from about 45% to about 85%, preferably from about 50% to about 75%, of water. Still another type of product can be formulated from a vehicle system in solution, which is an ointment. An ointment may comprise a simple base of animal or vegetable oils or hydrocarbons that are i-solid (oleaginous). The ointments may also comprise bases of absorption ointment, which absorb water to form emulsions. Ointment vehicles can also be soluble in water. An ointment may also comprise from about 2% to about 10% of an emollient more than about 0.1% to about 2% of a thickening agent. A more complete description of the thickening agents, useful herein, can be found in Sargain, Cosmetics Science and Tecnnolocry. 2a. edition, Vol. 1, p. 72-73 (1972). If the vehicle is formulated as an emulsion, preferably from about 1% to about 10%, most preferably from about 2% to about 5%, of the vehicle system comprises an emulsifier. The emulsifiers can be nonionic, anionic or cationic. Suitable emulsifiers are described, for example, in the U.S.A. 3,755,560, issued August 28, 1973, Dickert et al., Patent of E.U.A. 4,421,769, issued December 20, 1983, Dixon et al .; and McCutcheon s Detergents and Emulsifiers. North American Edition, pages. 317-324 (1986); the descriptions of which are incorporated herein by reference. Preferred emulsifiers are anionic or nonionic, although other types can also be used. Lotions and creams can be formulated as emulsions, as well as solutions. Typically, such lotions comprise from about 1% to about 20%, preferably from about 5% to about 10% of an emollient; from about 25% to about 75%, preferably from about 45% to about 95% water; and from about 0.1% to about 10%, preferably from about 0.5% to about 5% of an emulsifier. Said creams could typically comprise from about 1% to about 20%, preferably from about 5% to about 10% of an emollient; from about 20% to about 80%, preferably from about 30% to about 70% water; and from about 1% to about 10%, preferably from about 2% to about 5% of an emulsifier. Single-emulsion skin care preparations, such as lotions and creams, of the oil-in-water type and the water-in-oil type, are well known in the cosmetic art and are useful in this invention. The multi-phase emulsion compositions, such as those of the water-in-oil-in-water type, as described in the U.S.A. 4,254,105, Fakuda et al., Issued March 3, 1981, incorporated herein by reference, are also useful in this invention. In general, said individual or multi-phase emulsions contain water, emollients and emulsifiers, as essential ingredients. Also present in the present invention are triple emulsion vehicle systems, which comprise an oil-in-water silicone fluid emulsion composition, as described in the U.S.A. 4,960,764, Figueroa, issued October 2, 1990. Another emulsion vehicle system useful in topical compositions, is a micro-emulsion vehicle system. Said system comprises from about 9% to about 15% squalane; from about 25% to about 40% silicone oil; from about 8% to about 20% of a fatty alcohol; from about 15% to about 30% polyoxyethylene sorbitan monohydric acid (commercially available under the trade name of Tweens) or other noionics; and from about 7% to about 20% water. Liposomal formulations are also useful for the present invention. Said compositions can be prepared by first combining an anti-wrinkle agent in water and then this solution with a phospholipid, such as dipalmitolfosphatidyl-choline, cholesterol and water, according to the method described in Mezei & Gulasekharam, Liposomes - A Selective Drug Delivery System for the Topieal Route of Administration: Dosage Form Gel, Journal of Pharmaceutics and Pharmacology. Vol. 34 (1982), p. 473-474, incorporated herein by reference, or a modification thereto. The epidermal lipids of the compositions suitable for the formation of liposomes can be substituted for the phospholipid. The liposome preparation is then incorporated into one of the above topical vehicle systems (eg, a gel or an oil-in-water emulsion) to produce the liposomal formulation. Other pharmaceutical compositions and uses of topically applied liposomes are described in Mezei, M., Liposomes as a Skin Drug Delivery System, Topics in Pharmaceutical Sciences (D.D.Breimer and P. Speiser, editors), Elsevier Science Publishers B.V., New York, NY, 1985, pgs. 345-358, incorporated herein by reference. The method of reversed phase evaporation as described in Szoka and Papahadjopoulos, Procedure for Preparation of Liposomes with Large Internal Aqueous Space and High Capture by Reverse-Phase Evaporation, Proceeding of the National Academy of Science. Vol. 75 pp. 4194-4198 (1978), and also in DuPlessis, Egbaria and Weiner, Influence of Formulation Factors on the Deposition of Liposomal Components into the Different Strata of the Skin, Journal of the Society of Cosmetic Chemists. Vol. 43, pp.93-100 (1992) can also be used to make a liposomal dispersion of anti-wrinkle agent particularly useful, and is incorporated herein by reference. If the topical compositions useful in this invention are formulated as a gel or a stick, these compositions can be formulated by the addition of a suitable amount of a thickening agent, as described suppressed. to a cream or lotion formulation. Topical compositions, useful in this invention, are also formulated as makeup products, such as makeup bases. The bases for makeup are based on solutions or lotions with appropriate amounts of thickeners, pigments and fragrances. Topical compositions, useful in this invention, may contain, in addition to the aforementioned components, a variety of additional oil-soluble materials and / or water soluble materials, conventionally used in topical compositions, at their levels established in the art.

Various water-soluble materials may also be present in the compositions useful in this invention. These include humectants, proteins and polypeptides, preservatives and an alkaline agent. In addition, topical compositions, useful in this invention, may contain conventional, conventional auxiliaries, such as colorants, opacifiers (e.g., titanium dioxide), pigments and perfumes. Topical compositions, useful in this invention, may also include a safe and effective amount of a penetration enhancing agent. A preferred amount of the penetration enhancing agent is from about 1% to about 5% of the composition. Examples of penetration enhancers, among others, are described in the U.S.A. 4,537,776, Cooper, issued August 27, 1985 4,552, 872, Cooper et al., Issued November 12, 1985 4,557,934, Cooper, issued December 10, 1985 4,130,667, Smith, issued December 19, 1978 3,989,816, Rhaadhyaksha, issued on November 2, 1976 4,017,641, DiGuilio, issued on April 12, 1977; and 4,954,487, Cooper, Loomans & ickett, issued September 4, 1990. Additional penetration enhancers, useful in this invention, are described by Cooper, E.R., in Effect of Decylmethylsulfoxide on Skin Penetration, Solution Behavior of Surfactants. Vol. 2 (Mittal and Fendler, eds.), Plenum Publishing Corp., 1982, p. 1505-1516; Mahjour, M., B.

Mauser, Z. Rashidbaigi & M.B. Fawzi, Effect of Egg Yolk Lecithins and Commercial Soybean Lecithins on In Vitro Skin Permeation of Drugs, Journal of Controlled Relay. Vol 14 (1990), pgs. 243-252; Wong, 0., J. Huntington, R. Konishi, J.H. Rytting & T. Higuchi, Unsaturated Cyclic Ureas as New Nontoxic Biodegradable Transdermal Penetration Enhancers I: Synthesis, Journal of Pharmaceutical Sciences. Vol. 77, No. 11 (Nov. 1988), p. 967-971; Williams, A.C. & B.W. Barry, Terpenes and the Lipid-Protein-Partitioning Theory of Skin Penetration Enhancement, Pharmaceutical Research. Vol. 8, No. 1 (1991), p. 17-24; and Wong, 0., J. Huntington, T. Nishihata & J.H. Rytting, New Alkyl N, N-Dialkyl-Substituted Amino Acetates as Transdermal Penetration Enhancers, Pharmacuetical Research.Vol. 6, No. 4 (1989), p. 286-295. The above citations are incorporated herein by reference. In the compositions useful in this invention, other conventional skin care product additives may also be included. For example, collagen, hyaluronic acid, elastin, hydrosylates, narcissus oil, jojoba oil, epidermal growth factor, soy saponins, mucoplosaccharides and mixtures thereof can be used. Several vitamins may also be included in the compositions useful herein. For example, Vitamin A, and its derivatives, Vitamin B2, Bitumen, Pantothenic, Vitamin D, and mixtures thereof can be used.

CLEANING COMPOSITIONS Skin cleansing compositions, useful in this invention, comprise, in addition to the anti-wrinkle agent, a cosmetically acceptable surfactant. The term "cosmetically acceptable surfactant" refers to a surfactant, which is not only an effective cleanser of the skin, but can also be used without unduly exhibiting toxicity, irritation, allergic response, and the like. In addition, the surfactant must be capable of being mixed with the anti-wrinkle agent, such that there is no interaction that could substantially reduce the effectiveness of the composition to erase or prevent wrinkles in the skin. Skin cleansing compositions useful in this invention preferably contain from about 1% to about 90%, most preferably from about 5% to about 10%, of a cosmetically acceptable surfactant. The physical form of the cleansing compositions of the skin is not critical. The compositions can be formulated, for example, as toilet bars, liquids, pastes, or foams. The toilet bars are the most preferred, since this is the form, of the cleaning agent, most commonly used to wash the skin.

The surfactant component of the compositions, useful in this invention, is selected from the group consisting of anionic, nonionic, zwitterionic, amphoteric and ampholytic surfactants, as well as mixtures of these surfactants. Such surfactants are well known to those skilled in the art of detergency. Skin cleansing compositions useful in this invention may optionally contain, at their levels established in the art, materials that are conventionally used in skin cleansing compositions.

COMBINATION OF ASSETS; A. Solar Filters and Solar Blasts The regulation of wrinkles in the skin, resulting from exposure to ultraviolet light, can be achieved by using combinations of anti-wrinkle agents in the skin, together with sunscreens or sunscreens. Sunscreens include, for example, zinc oxide and titanium dioxide. Ultraviolet light is a predominant cause of wrinkling of the skin. Thus, for purposes of wrinkle prevention, the combination of an anti-wrinkle agent with a sunscreen containing UVA and / or UVB is desirable.

A wide variety of conventional sunscreen agents are suitable for use in combination with the anti-wrinkle agent. Segarin, and others, in Chapter VIII, p. 189 et. I know that. , from Cosmetics Sci nce and Technology. describe numerous suitable agents. Suitable, specific sunscreen agents include, for example: p-aminobenzoic acid, its salts and its derivatives (ethyl, isobutyl, glyceryl esters, p-dimethylaminobenzoic acid); anthranilates (ie, o-aminobenzoates; methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl ester); salicylates (amyl, phenyl, benzyl, menthyl, glyceryl, and dipropylene glycol esters), cinnamic acid derivatives (menthyl and benzyl esters, O-phenyl-cinnamonitrile, butyl cinnamoyl-pyruvate); dihydroxycinnamic acid derivatives (umbelliferone, methylumbelliferone, methylaceto-unbeliferone); trihydroxycinnamic acid derivatives (esculetin, metilesculetin, dafnetin and the glycosides esculin and daphnin); hydrocarbons (diphenylbutadiene, stilbene), - dibenzalacetone and benzal acetophenone; napholsulfonates (sodium salts of 2-naphthol-3,6-disulfonic and 2-naphthol-6,8-disulfonic acids); dihydroxy naphthoic acid and its salts; o- and p-hydroxybiphenyl disulfonates; coumarin derivatives (7-hydroxy, 7-methyl, 3. phenyl); diazoles (2-acetyl-3-bomoimidazole, phenyl benzoxazole, methyl naphthoxazole, various aryl benzothiazoles); quinine salts (bisulfate, sulfate, chloride, oleate, and tannate); quinoline derivatives (salts of 8-hydroxyquinoline, 2-phenylquinoline); hydroxy- or methoxy-substituted benzophenones; uric and vilouric acids; tannic acid and its derivatives (e.g., hexaethyl ether); ether (butyl carbothol) (piperonyl 6-propyl); nemzofenonas (oxybenzene, sulisobenzone, dioxybenzone, benzoresorcinol, 2,2, 4,4 - tet enone rahidroxibenzof, 2,2 dihydroxy-4-4-f -dimetoxibenzo enone, octabenzone; 4-isopropyldibenzoylmethane; butylmethoxydibenzoylmethane 4,4--t; and etocrylene. of these, preferred are p-methoxycinnamate, 2-ethylhexyl, 4,4 -t-butyl methoxydibenzoylmethane, 2-hydroxy-4-enone metoxibenzof acid octyldimethyl-p-aminobenzoic diagaloilo trioleate, 2,2-dihydroxy -4-methoxybenzophenone, 4- (bis (hydroxypropyl)) aminobenzoate, 2-cyano-3,3-diphenylacrylate, 2-ethylhexyl salicylate, 2-ethylhexyl p-aminobenzoate, glyceryl 3,3,5 -trimetilciclohexilo, methylanthranilate, p-dimethyl-aminobenzoic acid or aminobenzoate, p-dimethyl-aminobenzoate 2-ethylhexyl-phenylbenzimidazole-5-sulphonic acid 2, 2- (p-dimetilaminof enyl) -5 phonic -sul - benzoxazoic, and mixtures of these compounds.The highly preferred sunscreens in the compositions, useful in this invention, are p-me 2-ethylhexyl toxicinamate, 4,4-butylmethoxydibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octyldimethyl-p-aminobenzoic acid and mixtures thereof.

Also particularly useful in the compositions are sunscreens such as those described in the U.S.A. No. 4,937,379, issued to Sabatelli on June 26, 1990, and the patent of E.U.A. No. 4,999,186, issued to Sabatelli & Spinark on March 12, 1991, both incorporated here by reference. The sunscreen agents described therein have, in a single molecule, two different chromophore portions, which exhibit different ultra violet radiation absorption spectra. One portion of the chromophore absorbs predominantly on the UVB radiation scale and the other abnsorbs strongly on the UVA radiation scale. Preferred members of this class of sunscreen agent are 4-N, N- (2-ethylhexymethoxybenzoic acid ester of 2,4-dihydroxybenzophenone, N, N-di- (2-ethylhexyl) -4-aminobenzoic acid ester with 4-hydroxydibenzoylmethane; ester of 4-N, N- (2-ethylhexyl) 4-hidroxidibenzometano -metilaminobenzoico with; ester of 4-N, N- (2-ethylhexyl) -metilaminobenzoico with 2-hydroxy-4- ( 2-hydroxy-ethoxyJ-benzophenone; 4-N, N- (2-ethylhexyl) -methylaminobenzoic acid ester of 4- (2-hydroxyethoxy) -dibenzoylmethane; N, N-di- (2-ethylhexyl) -4- ester aminobenzoic 2-hydroxy-4- (2-hydroxyethoxy) benzophenone; and ester N, N-di- (2-ethylhexyl) -4-aminobenzoic 4 - (2-hydroxyethoxy) dibenzoylmethane, and mixtures thereof.

A safe and effective amount of sunscreen can be used in the anti-wrinkle agent compositions useful in this invention. The sunscreen agent must be compatible with the anti-wrinkle agent. The composition preferably contains from about 1% to about 20%, most preferably from about 2% to about 10% of a sunscreen agent. The exact amounts will vary depending on the chosen sunscreen and the desired Sun Protection Factor (SPF). An agent can also be added to any of the compositions useful in this invention, to improve the substantive character of the skin of those compositions, particularly to improve their resistance to being removed with water or rubbed. A preferred agent, which will provide this benefit, is a copolymer of ethylene and acrylic acid. The compositions comprising this copolymer are described in the U.S.A. 4,663,157, Brock, issued May 5, 1987, which is incorporated herein by reference.

B. Anti-inflammatory Agents In a preferred wrinkle regulating composition in this invention, an anti-inflammatory agent is included as an active agent together with the anti-wrinkle agent. The inclusion of an anti-inflammatory agent improves the wrinkle regulating benefits of the skin of the compositions. The anti-inflammatory agent provides strong protection in the UVA radiation scale (although it also provides some UVB protection). The topical use of anti-inflammatory agents reduces the darkening of the skin resulting from chronic exposure to UV radiation. (See U.S. Patent 4,847,071, Bissett, Bush and Chatterjee, issued July 11, 1989, incorporated herein by reference.; and patent of E.U.A. 4,847,069, Bissett and Chatterjee, issued July 11, 1989, incorporated herein by reference). A safe and effective amount of an anti-inflammatory agent can be added to the compositions useful in this invention, preferably from about 0.1% to about 10%, most preferably from about 0.5% to about 5%, of the composition. The exact amount of the anti-inflammatory agent, which will be used in the compositions, will depend on the particular anti-inflammatory agent used, since said agents vary widely in potency. Steroidal anti-inflammatory agents may be used, including, but not limited to, corticosteroids such as hydrocortisone, hydroxyvitrazinone, alpha-methyl dexamethasone, dexamethasone phosphate, beclomethasone dipriopionate, clobetasol valerate, desonide, deoxymethasone, deoxymethasone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, lucilolone-acetonide, fludrocortisone, flumethasone pivalate, fluosinolone-acetonide, flucinonide, flucortin butyl ester, f lucortolone, fluprednidene acetate (flupredilidene), flurandrenolone, hacinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone-acetonide, cortisone, shortdoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradenolone-acetonide, medrisone, amcinafel, amcinafide, betamethasone and the rest of their esters, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolons, d iclorisone, difluprednate, flucloronide, flunisolide, fluorometalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocostisone cyclopentylpropionate, hydrocortamate, meprednisone, parametsone, prednisolone, prednisone, beclomethasone dipriopionate, triamcinolone and mixtures thereof. The preferred anti-inflammatory steroid to be used is hydrocortisone. A second class of anti-inflammatory agents, which is useful in the compositions, includes non-steroidal anti-inflammatory agents. The variety of compounds encompassed by this group is well known to those skilled in the art. For a detailed description of the chemical structure, synthesis, side effects, etc. , of non-steroidal anti-inflammatory agents, reference is made to normal texts, which include, Anti-inf lammatory and Anti-Rheumatic Drugs. K.D. Rainsford, Vol. I-III, CRC Press, Boca Raton (1985), and Anti- Inflammatory Agents. Chemistry and Pharmacology. 1, R.A. Scherrer, and others, Academic Press, New York (1974). Non-steroidal anti-inflammatory agents useful in the compositions of this invention include, but are not limited to: 1) oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam and CP-14,304; 2) salicylates, such as aspirin, disalcide, benorilate, trisylate, safaprin, solprine, diflunisal and fendosal; 3) acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, thiopinac, zidomethacin, acetaminophen, fentiazac, zomepiract, clidanac, oxepinac and felbinac; 4) the fenamates, such as mefenamic, meclofenamic, flufenamic, niflumic and tolfenamic acids; 5) propionic acid derivatives, such as ibuprofen, naproxen, benxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, thioxaprofen, suprofen, alminoprofen and thiaprofenic; 6) pyrazoles, such as fenibutazone, oxyphenbutazone, feprazone, azapropazone and trimetazone. Mixtures of these non-steroidal anti-inflammatory agents can also be employed, as well as the pharmaceutically acceptable salts and esters of these agents. For example, etofenamate, a flufenamic acid derivative, is particularly useful for topical application. Of the nonsteroidal anti-inflammatory agents, the preferred ones are ibuprofen, naproxen, flufenamic acid, mefenamic acid; meclofenamic acid, piroxicama and felbinac; the most preferred are ibuprofen, naproxen, and flufenamic acid. Another class of anti-inflammatory agents, which may be useful in the compositions of this invention, are the anti-inflammatory agents described in the US patent. No. 4,708,966, Loomans et al., Issued November 24, 1987. This patent discloses a number of non-steroidal anti-inflammatory compounds, comprising specifically substituted phenyl compounds, especially substituted derivatives of 2,6-di-tert-butyl phenol. For example, the compounds selected from 4- (4 -pentin-3 -ona) -2,6-di-t-butylphenol are useful in the methods of this invention; 4- (5-hexanoyl) -2,6-di-t-butylphenol; 4 - ((S) - (-) - 3 -methyl-5-hexanoyl) -2,6-di-t-butylphenol; 4 - ((R) - (+) - 3 -methyl-5-hexanoyl) -2,6-di- [beta] -butylphenol; and 4- (3,3-dimethoxypropionyl) -2,6-di-t-butylphenol; the most preferred is 4- (5-hexanoyl) -2,6-di-t-butylphenol. Still another class of anti-inflammatory agents, which are useful in the compositions herein, are those described in the U.S.A. No. 4,912,248, Mueller, issued March 27, 1990. This patent describes diastereomeric compounds and mixtures of ester-specific compounds containing 2-naphthyl, especially naproxen ester and naproxol ester compounds, having two or more chiral centers. For example, the compounds selected from (S) -naproxen- (S) -2-butyl ester, (S) -naproxen- (R) -2-butyl ester, butyrate (S) -naproxol- ( R) -2-methyl, butyrate (S) -naproxol- (S) -2-methyl, diastereomer mixtures of ester (S) -naproxen- (S) -2-butyl and ester (S) -naproxen- (R) ) -2-butyl, and diastereomer mixtures of butyrate (S) -naproxol- (R) -2-methyl and butyrate (S) -naproxol- (S) -2-methyl. Finally, so-called natural anti-inflammatory agents are useful in methods of this invention. For example, candelilla wax, alpha-bisabolol, aloe vera, Manjistha (extracted from plants in the genus Rubia, particularly Rubia Cordifolia), and Guggal (extracted from plants of the genus Co miphora, particularly Commiphora Mukul) can be used. Another preferred composition useful in this invention, comprises an anti-wrinkle agent, a sunscreen, and an anti-inflammatory agent, as a whole, to regulate wrinkles in the amounts described, for each, above.

C. Antioxidants / Radical Sweepers In a preferred skin wrinkle regulating composition useful in this invention, an antioxidant / radical scavenger is included as an active agent together with the anti-wrinkle agent. The inclusion of a radical antioxidant / scavenger improves the wrinkle regulating benefits of the skin of the composition. A safe and effective amount of a radical antioxidant / scavenger may be added to the compositions useful in this invention, preferably from about 0.1% to about 10%, most preferably from about 1% to about 5% of the composition. Radical antioxidants / scavengers may be used, such as ascorbic acid (vitamin C) and its salts, tocopherol (vitamin E), tocopherol sorbate, other tocopherol esters, butylated hydroxybenzoic acids and t salts, 6-hydroxy-2, 5 acid, 7,8-tetramethylchroman-2-carboxylic acid (commercially available under the tradename of Troxol R), gallic acid and its alkyl esters, especially propyl gallate, uric acid and its alkyl salts and esters, sorbic acid and its salts, ascorbic esters of fatty acids, amines (e.g., N, N-diethylhydroxylamine, amino guanidine), sulfhydryl compounds (e.g., glutathione), and fumaric dihydroxy acid and its salts. In a preferred wrinkle regulating composition useful in this invention, the compositions comprise one, either or both, of a sunscreen agent, anti-inflammatory agent, and / or antioxidant / radical scavenger, included as active agents together with the anti-wrinkle agent. The inclusion of two or all three of these agents with the anti-wrinkle agent of the skin improves the wrinkle-regulating benefits of the compositions.

D. Chelators In a preferred wrinkle regulating composition useful in this invention, a chelating agent is included as an active agent together with the anti-wrinkle agent. As used herein, chelating agent means an active agent capable of removing a metal ion from a system forming a complex, so that the metal ion can not readily precipitate on or catalyze chemical reactions. The inclusion of a chelating agent improves the wrinkle regulating benefits of the composition. A safe and effective amount of a chelating agent can be added to the compositions useful in this invention, preferably from about 0.1% to about 10%, most preferably from about 1% to about 5%, of the composition. Chelating agents useful in the compositions are described in a U.S. patent application. Series No. 619,805, Bissett Bush & Chartterjee, filed on November 27, 1990 (which is a continuation in part of the patent application of E.U.A. Series No. 251,910, filed on October 4, 1988); patent application of E.U.A. Series No. 514,892, Bush & Bissett, presented on April 26, 1990; and patent application of E.U.A. Series No. 657,847, Bush, Bissett & Chatterjee, filed on February 25, 1991; all of these are incorporated here by reference. Preferred chelating agents useful in the compositions of this invention are fluryl-di-oxime and its derivatives. In a preferred wrinkle regulating composition useful in this invention, the compositions comprise either one of the two, any of the three, or the four of a sunscreen agent, anti-inflammatory agent, antioxidant / sweeping agent and / or radical scavenger and / or chelating agent, included as active agents together with the anti-wrinkle agent. The inclusion of two, three or all four of these agents with the anti-wrinkle agent improves the wrinkle-regulating benefits of the compositions.

E. Retinoids In a preferred wrinkle regulating composition useful in this invention, a retinoid, preferably retinal acid, is included as an active agent together with the anti-wrinkle agent. The inclusion of a retinoid improves the skin wrinkle regulating benefits of the composition. A safe and effective amount of a retinoid can be added to the compositions, useful in this invention, preferably from about 0.001% to about 2%, most preferably from about 0.01% to about 1% of the composition. As used herein, retinoid includes all natural and / or synthetic analogs of Vitamin A or retinol-like compounds, which possess the biological activity of Vitamin A in the skin, as well as the geometric isomers and stereoisomers of these compounds, such as trans-retinoic acid and 13-cis-retinoic acid. In a preferred wrinkle regulating composition useful in this invention, the compositions comprise either one of the two, any of the three, any of the four, and / or the five of a sunscreen agent, anti-inflammatory agent, antioxidant / radical scavenger, chelating agent, and / or a retinoid included as active agents together with the anti-wrinkle agent. The inclusion of two, three, four, or all five of these agents with the anti-wrinkle agent improves the wrinkle-regulating benefits of the compositions.

METHODS FOR USING POLYOL DERIVATIVES This invention relates to methods for regulating wrinkles and / or atrophies in the skin of a mammal. Said methods comprise the topical application of a safe and effective amount of an anti-wrinkle agent. The amount of anti-wrinkle agent and the frequency of application will vary widely depending on the levels of wrinkles existing in the subject, the rate of additional wrinkle formation, and the level of regulation desired. The wrinkle regulation that involves the prevention or delay of wrinkling is preferred. Very preferred is the regulation of wrinkling that involves scraping of existing wrinkles. A safe and effective amount of the anti-wrinkle agent is applied, in a topical composition, generally from about 0.001 g to about 1000 g per cm2 of the skin per application, preferably from about 1 g to about 500 g / cm2 of the skin per application, preferably from about 10 g to about 300 g / cm2 of the skin, most preferably from about 20 g to about 200 g / cm2 of the skin. The application preferably varies from about weekly to about 10 times a day, preferably from about twice a week to about four times a day, still preferably from about three times a week to about twice a day, most preferably once a day. A minimum treatment of about four weeks is preferred for a reparative age benefit, more preferably a minimum of eight weeks, most preferably a minimum of twelve weeks. A preferred method of this invention for regulating wrinkles of mammalian skin involves applying both a safe and effective amount of the wrinkle agent and a safe and effective amount of one or more of a sunscreen agent, an anti-inflammatory agent, a antioxidant agent / radical scavenger, a chelating agent and / or a retinoid to the skin, simultaneously. As used herein, simultaneous application or simultaneously means applying the agents to the skin, in the same places on the body at approximately the same time. Although this can be achieved by applying these agents separately to the skin, preferably, a composition comprising all desired, mixed agents is applied to the skin. The amount of sunscreen agent is preferably about 0. 05 mg to approximately 0.5 mg per cm2 of the skin. The amount of anti-inflammatory agent applied is preferably from about 0.005 mg to about 0.5 mg, most preferably from about 0.01 mg to about 0. 11 mg per cm2 of the skin. The amount of antioxidant agent / radical scavenger applied to the skin is preferably from about 0.01 mg to about 1.0 mg, most preferably about 0. 05 mg approximately 0.5 mg per cm2 of the skin. The amount of chelating agent applied to the skin, preferably is about. 001 mg to about 1.0 mg, most preferably about 0. 01 mg to approximately 0. 5 mg, still preferably from about 0.05 mg to about 0.1 mg per cm2 of the skin. The amount of retinoid applied to the skin is preferably from about 0.001 mg to about 0.5 mg per cm2 of the skin, most preferably from about 0.005 mg to about 0.1 mg per cm2 of the skin. The amount of anti-wrinkle agent applied to the skin is preferably from about 0.001 mg to about 2 mg per cm2 of the skin, per application, most preferably from about 0.01 mg to about 1 mg per cm2 of the skin, per application. Another preferred method of this invention involves the application of a safe and effective amount of an anti-wrinkle agent in a cream or conductive gel, followed by the controlled application of an electric field having such a polarity that they direct the anti-wrinkle agent to be negatively charged to the skin. . This method, known as cathodal iontophoresis, is described in A.K. Banga and Y.W. Chien,Iontophoretic Delivery of Drugs: Funamentals, Develpments, and Biomedical Applications J. Controlled Relay Vol. 7, pp. 1-24 (1988) and references therein, incorporated herein by reference. Examples are also given in R.R. Burnette, Iontophoresis, J. Hadgraft and R.H. Guy (editors), Transdermal Drug Delivery: Developmental Issues and Research Initiatives.

Macerl Dekker, New York, NY, 1989, p. 247-291 and references there, and in G.B. Kasting, E.W. Merritt, and J.C. Keister, An In Vitro Method for Studying the Iontophoretic Enhancement of Drug Transport Thruough Skin, Jounal of Membrane Science. Vol. 35, pp. 137-159, (1988) and references thereto, incorporated herein by reference. In said method the anti-wrinkle agent solution is applied to the skin and contacted by the cathode of a suitable electrical device to supply a controlled voltage or current to the skin. The circuit is completed by placing the anode of the device on the skin at a point removed from the delivery site. The electric field (ie, voltage or current) can be either pulsed, sinusoidal or continuous wave as described in the references above. The application time of the field varies from about 1 minute to about 24 hours, preferably from about 1 to about 30 minutes, more preferably from about 2 minutes to about 5 minutes. A series of high voltage pulses followed by continuous cathodic iontophoresis can also be used, as described in M.R. Prausnitz, V.G. Bose, R. Langer, and J.C. Weaver, Electroporationof Mammalian Skin: A Mechanism to Enhace Transdermal Drug Delivery, Proceedings of the National Academy of Sciences (USA). Vol. 90, pp. 10504-10508, (1993) and references thereto, incorporated herein by reference. In all cases, the electric field is applied in a safe and effective manner, so that the anti-wrinkle agent is delivered through the skin without undue discomfort or irritation to the subject.

The polyol derivatives herein may also be useful for one or more of the following: regulation of dryness, regulation of dark circles, reduction of pore size, improvements in skin color / brightness / pinkness, reduction of stretch and improve the firmness of the skin, and make the skin smoother. The following examples further describe and demonstrate the preferred embodiments within the scope of this invention. The examples are given only for purposes of illustration, and should not be construed as limitations of the present invention, since many variations thereof are possible without departing from their spirit and scope.

EXAMPLES 1-3 A simple solution was prepared by combining the following components using conventional mixing techniques: COMPONENT EXAMPLE NO. 1 2 3 Dodecasodium salt of myo-inositol hexakisphosphate 1 - - Hexapotasium salt of myó-inositol hexakissulfate - 2 Acid myo-inositol hexakisphosphoric acid (pythic acid) - - 10 50% solution in water triethanolamine 99% 5 phosphoric acid, 80% 0.25 0.25-propylene glycol 30 30 30 ethanol, absolute 30 20 20 deionized water 100% balance This composition is useful for topical application to regulate wrinkles in the skin. The composition is applied to the skin at a level of 1 mg / cm2 once per day, for a period of six months. Cathodic inotophoresis is used for 2 minutes per application at a current density of 0.050 ma / cm2, to improve the supply of the anti-wrinkle agent in the skin.

EXAMPLES 4-7 An oil-in-water emulsion was prepared by combining the following components using conventional mixing techniques: COMPONENT EXAMPLE NO. 4 5 6 7 myo-inositol hexakis sulfuric acid, 50% solution in water 6 myo-inositol hexakis phosphoric acid, 50% solution in water 4 1,2,3,4,5-cyclopentanpentol-sulfuric acid 6 acid 1, 2,3,4,5,6,7-cycloheptanheptol-phosphoric acid. . . 6 glycerin 3 3 3 3 methyl paraben 0.2 0.2 0.2 0.2 stearate 20 (Brij 78R) 1 1 1 1 Glycerin monostearate and PEG 100 (Arlacel 165R) 0.5 0.5 0.5 0.5 Carbopol 940 0.2 0.2 0.2 0.2 Cetyl alcohol 1 1 1 1 Stearyl alcohol 1 1 1 1 Propylparaben 0.1 0.1 0.1 0.1 Diisopropyl diperate 2 2 2 2 C12-C15 alcohol benzoate 6 6 6 6 Imidazolidinal urea 0.3 0.3 0.3 0.3 Ammonium hydroxide, 30% solution 1.6 1.6 1.6 1.6 deionized water 100% balance This composition is useful for topical application to regulate wrinkles in the skin. A sufficient amount is used to deposit 20 g / cm2 of anti-wrinkle agent to the skin. The composition is applied three times a day for one year.

EXAMPLES 8-11 A clear gel was prepared by combining the following components using conventional mixing techniques: COMPONENT EXAMPLE NO. 8 9 10 11 myó-inositol hexakis phosphoric acid, 50% solution in water 0.5 - myo-inositol hexakis sulfuric acid, 50% solution in water 0.5 - myo-inositol hexakis phosphoric acid, 50% solution in water acid myo- inositol hexakis sulfonic, 50% solution in water Carbopol 980 0.55 0.5 0.5 0.5 EDTA disodium 0.02 0.02 0.02 0.02 triethanolamine 99% 2 1.2 2 1.2 propylene glycol 3 3 3 3 methyl paraben 0.2 0.2 0.2 0.2 deionized water 100% balance This composition is useful for topical application to regulate wrinkles in the skin. A sufficient amount is used to deposit 20 g / cm2 of anti-wrinkle agent to the skin. The composition is applied twice a day during the individual's life.

EXAMPLES 12-15 An oil-in-water emulsion was prepared by combining the following components using conventional mixing techniques: COMPONENT EXAMPLE NO. 12 13 14 15 myo-inositol hexakis phosphoric acid, 50% solution in water 3 - - myo-inositol hexakis sulfuric acid, 50% solution in water - 0.1 - Cetyltrimethylammonium salt of myo-inositol hexakisphosphate - - 0.1 -sal of myo-inositol-hexakisphosphate cetylpyridine - - - 0.1 Carbopol 954 0.2 0.2 0.2 0.2 Pemulen TR-2 0.15 0.15 0.15 0.15 glycerin 3 3 3 3 cetyl palmitate 2 2 2 2 methyl paraben 0.2 0.2 0.2 0.2 stearoxi trimethylsilane and stearyl alcohol 1 1 1 1 squalane 6 6 6 6 propylparaben 0.1 0.1 0.1 0.1 methyl paraben 0.2 0.2 0.2 0.2 imidazolidinal urea 0.3 0.3 0.3 0.3 ammonium hydroxide, 30% solution 5 3 - -triethanolamine 99% - - 0.35 0.35 deionized water 100% balance This composition is useful for topical application to regulate wrinkles in the skin. A sufficient amount is used to deposit 1 g / cm2 of anti-wrinkle agent to the skin. The composition is applied once a week for a period of three years.

EXAMPLES 16-19 An oil-in-water microemulsion was prepared by combining the following components using conventional mixing techniques: COMPONENT EXAMPLE NO. 16 17 18 19 dodecasodic salt of myó-inositol hexakisphosphate 1.5-hexosodic salt of myó-inositol hexakis sulfate-1.5-myo-inositol hexakis phosphoric acid, 50% solution in water - - 3-myo-inositol hexakis sulfuric acid, 50% solution in water 3 phosphoric acid, 85% solution 0.4 0.2 ammonium hydroxide, 30% solution - - 1.5 1 Sorbitan monolaurate PEG4 22.5 22.5 22.5 22.5 sorbitan monoolate PEG5 2.5 2.5 2.5 2.5 Cetearyl octanoate 25 25 25 25 DMDM hydantoin and 3-iodo-2-propynylbutyl carbamate (Glydant Plus) 0.2 0.2 0.2 0.2 deionized water 100% balance This composition is useful for topical application to regulate wrinkles in the skin. A sufficient amount is used to deposit 20 g / cm2 of anti-wrinkle agent to the skin. The composition is applied three times a week for a period of five years. Since the appropriate embodiments of this invention have been described, it will be obvious to those skilled in the art that various changes and modifications can be made to this invention, without departing from the spirit and scope of the invention. It is intended to cover, in the appended claims, such modifications that are within the scope of the invention.

Claims (10)

NOVELTY OF THE INVENTION CLAIMS

1 . A composition for topical application, useful for the regulation of wrinkles in the skin, characterized in that it comprises: a) a safe and effective amount of a cyclic polyanionic polyol derivative having the structure: where n is an integer from 1 to 3 and each X is, independently, selected from the group consisting of 0S03-, OP03-, S03-, P03-, C02-, and OH; with at least three X being different from OH; b) cations that balance the charge of the derivative of a); c) a safe and effective amount of a sunscreen; and d) a topical vehicle comprising an emollient.

2. A composition for topical application, useful for the regulation of wrinkles in the skin, according to claim 1, further characterized in that a) the cation (s) are selected from H +, Na +, K +, Ca ++, Mg ++ , Al2 (OH) 5+, NH4 +, (HOCH2CH2) 3NH +, (CH3CH2) 3NH +, HOCH2 (CH3) 2CNH3 +, (HOCH2) 3CNH3 +, CH3 (HOCH2) 2CNH3 +, CH3CH2 (HOCH2) 2CNH3 +, (CH3CH2) 4N, C16HJ3 ( CH3) 3N + and (NC16H33) C5H4N + and mixtures thereof; and b) each X is, independently, selected from the group consisting of 0P03 =, 0S03- and OH.

3. A composition for topical application, useful for the regulation of wrinkles in the skin, according to any of the preceding claims, further characterized in that it comprises from 0.5% to 5% of the polyol derivative.

4. A composition for topical application, useful for the regulation of wrinkles in the skin, according to any of the preceding claims, further characterized in that the polyol is delivered to the skin by catodal iontophoresis.

5. A composition for topical application, useful for the regulation of wrinkles in the skin, according to any of the preceding claims, further characterized in that X is 0P03 = or 0S03-.

6. A composition for topical application, useful for the regulation of wrinkles in the skin, according to any of the preceding claims, further characterized in that a) X is 0P03 =, b) n is 1 or 2, and e) at least 5 of the X are different from OH.

7. A composition for topical application, useful for the regulation of wrinkles in the skin, according to any of the preceding claims, further characterized in that the composition comprises less than 1% by weight of Cl "and the composition is substantially free of C03 A composition for topical application, useful for the regulation of wrinkles in the skin, according to any of the preceding claims, further characterized in that the amount of the polyol derivative, when applied to the skin, will result in the concentration from 0.001 g / cm2 to 1000 g / cm2 9. A composition for topical application, useful for the regulation of wrinkles in the skin, according to any of the preceding claims, further characterized in that the composition comprises 0.5% or more in weight of one or more of the following: inorganic phosphate, S04 =, or a combination of inorganic phosphate and S04 = 10. The use of the compounds The invention relates to compositions for the preparation of a composition for topical application, useful for the regulation of wrinkles in the skin, according to any of the preceding claims, characterized in that the components comprise: a) a safe and effective amount of a polyanionic polyol derivative cyclic having the structure: where n is an integer of 1 a and ca a X is, independently, selected from the group consisting of 0S03-, OP03-, S03-, P03-, C02-, and OH; with at least three X being different from OH; b) cations that balance the charge of the derivative of a); i? c) a safe and effective amount of a sunscreen; d) a topical vehicle comprising nan emollient. fifteen twenty 25 EXTRACT OF DISCLOSURE The object of the present invention relates to methods for regulating wrinkles in the skin and / or atrophy in mammalian skin which comprises applying topically to the skin of a mammal in need of treatment a composition that compresses a safe and effective amount of a cyclic polyanionic polyol derivative having the structure I, wherein n is an integer from 1 to 3; and each X is, independently, selected from the group consisting of OS03-, OP03-, S03-, P03-, C02-, and OH; with at least 3 X being different from OH. (you