CZ20014132A3 - A method of regulating visible and/or tactile discontinuities in the texture of mammalian skin and composition suitable for making the same - Google Patents

Abstract

The present invention relates to various methods for regulating the condition of mammalian keratinous tissue wherein the methods comprise the step of topically applying to the keratinous tissue of a mammal in need of such treatment a safe and effective amount of a composition comprising: a) a safe and effective amount of a repair agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine, and combinations thereof; and b) a dermatologically acceptable carrier for the repair agent. In particular embodiments, such compositions or modified versions thereof are suitable for regulating visible and/or tactile discontinuities in the texture of mammalian skin, preventing and/or retarding the appearance of spider vessels and/or red blotchiness on mammalian skin, preventing and/or retarding the appearance of dark circles under the eye of a mammal as well as their puffy eyes, desquamating mammalian skin, preventing and/or retarding sallowness of mammalian skin, preventing and/or retarding sagging of mammalian skin, softening and/or smoothing lips, hair and nails of a mammal, and preventing and/or relieving itch of mammalian skin.

Description

METHOD OF RECTIFICATION OF VISIBLE AND / OR TOUCH CONCERNS IN TISSUE MAMMAL SKIN AND MEANS

This application is for the replacement of US Provisional Application No. 60/134,660, filed May 18, 1999.

Technical field

The present invention relates to methods for regulating the condition of mammalian keratin tissue by applying selected xanthine compounds, the methods comprising: a) rectifying visible and / or tactile discontinuities in mammalian skin tissue, b) preventing and / or retarding the occurrence of spider vessels and / or reddish spots on (c) preventing and / or slowing the appearance of dark circles under the eyes of mammals as well as swollen eyes; (d) preventing and / or retarding the yellowness of the mammalian skin;

(e) preventing and / or retarding sagging of mammalian skin;

(f) desquamation of mammalian skin; (g) softening and / or smoothing of mammalian lips, hair and nails; and (h) preventing and / or relieving itching of the mammalian skin. These methods are carried out by topical application of compositions containing selected xanthine compounds to the keratin tissue of a mammal in need of such treatment.

BACKGROUND OF THE INVENTION

There are now a large number of personal care products available to consumers aimed at improving the health and physical appearance of the skin. Most of these products are aimed at delaying, minimizing or even eliminating wrinkle formation and other histological changes typically associated with aging of the skin or external damage to human skin.

Mammalian keratin tissue, especially human skin, is exposed to various damage by both external and internal factors. Such external factors include ultraviolet radiation, ambient contamination, wind, heat, infrared radiation, low humidity, unsafe detergents, abrasives, etc. Internal factors, on the other hand, include chronological aging and other biological changes from within the skin. Whether external or internal, these factors result in visible signs of skin damage. Typical skin damage includes uneven tissue, spider catheters or reddish spots, eye circles, swollen eyes,

yellowness, sagging, dead skin, rough skin, hair and / or nails, skin irritation resulting in itching.

Therefore, products and methods that seek to remedy these conditions of keratin tissue are needed so that the condition of keratin tissues, such as the skin of the hair and nails, is rectified.

Applicants have found that topical formulations containing certain xanthine compounds can be used to provide prophylactic and therapeutic treatment of these conditions of keratin tissue. Applicants have found, for example, that such compositions may be suitable for treating uneven tissue, spider catheters or reddish spots, sidestreams, swollen eyes, yellowness, skin sagging, dead skin, coarse keratin tissue such as skin, hair and / or nails, and skin irritation resulting in itching.

SUMMARY OF THE INVENTION

The present invention relates to methods for regulating the condition of mammalian keratin tissue, the methods comprising the step of topically applying a safe and effective amount of a composition to a mammalian keratin tissue in need of such treatment comprising:

(a) a safe and effective amount of a chemical condition enhancer consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and

(b) a dermatologically acceptable carrier of a chemical composition for improving health.

In certain embodiments, the compositions, or modified versions thereof, are useful for controlling visible and / or tactile discontinuities in mammalian skin tissue, preventing and / or retarding the appearance of spider vessels and / or reddish spots on the mammalian skin, preventing and / or retarding dark eye circles. mammals and also their swollen eyes, desquamating the mammalian skin, preventing and / or retarding the yellowness of the mammalian skin, preventing and / or retarding sagging of the mammalian skin, softening and / or smoothing the lips, hair and nails of mammals, and preventing and / or relieving itching.

All percentages and ratios used herein are weight percentages and ratios of total composition, and all measurements made, unless otherwise indicated, are at 25 ° C.

• · · ·

The compositions of the present invention may comprise, consist essentially of, or consist of the basic and optional ingredients and components described herein. "Essentially consisting of" as used herein means that the composition or component may include other ingredients, but only if the other ingredients do not substantially alter the essential and novel properties of the claimed compositions or methods.

All publications cited herein are hereby incorporated by reference in their entirety.

The term "keratin tissue" as used herein refers to keratin-containing layers which are arranged as the outermost protective cover for mammals, including, for example, skin, hair and nails (eg, nails, finger nails, hooves, cuticles, etc.).

The term "dermatologically acceptable" as used herein means that the compositions or components thereof described herein are suitable for use in contact with human keratin tissue without undue toxicity, intolerance, instability, allergic reactions and the like.

The term "safe and effective amount" as used herein means an amount of a compound or composition sufficient to produce a positive benefit, preferably a positive benefit of keratin tissue appearance or sensation, including, independently, a benefit described herein but small enough to avoid side effects that is, to provide a reasonable contribution to the risk ratio within the sound judgment of the practitioner.

The terms "desquamation, peeling and / or increasing conversion" as used herein mean the removal of the upper stratum corneum (containing the horn and granular layers). Without intending to be limited by theory, we believe that these benefits can be achieved by chemical and physical means that remove these layers from the surface. In addition, it is possible to induce separation by biological means which accelerates the conversion of epidermal layers from the base layers upwards. We believe that this induces a process of keratinocyte growth and induction of differentiation. The latter also leads to uplift at keratinization levels, which ultimately leads to a reorganization of the upper epidermal layers containing the stratum corneum layers and the granular layer.

The term "sagging" as used herein means laxity, slackness, or the like of the skin that occurs as a result of loss, damage, alterations and / or abnormalities in the skin elastin.

The terms " smoothing & softening ", as used herein, mean such a transformation of keratin tissue that its feel is better.

The compositions of the invention are suitable for topical application and for regulating the condition of keratin tissue. Rectifying the condition of keratin tissue is often required due to conditions that may be induced or caused by internal and / or external factors.

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In particular, "skin condition" includes prophylactic and / or therapeutic skin condition including prevention of loss of skin elasticity (loss and / or deactivation of functional skin elastin) such as elastosis, sagging, loss of skin return from deformation; non-melanin skin discoloration such as eye circles, spots (eg, uneven reddish discoloration caused, eg, by rosacea), yellowness (pale color), discoloration due to dilated capillaries or spider vessels. As used herein, prophylactic rectification of the skin condition includes delaying, minimizing and / or preventing visible and / or tactile discontinuities of the skin. As used herein, therapeutic treatment of the skin condition includes improving, eg, reducing, minimizing, and / or eliminating skin discontinuities. Reducing skin condition involves improving skin appearance and / or sensation, particularly facial skin (eg, controlling visible and / or tactile discontinuities in the structure of mammalian skin).

As used herein, "skin condition rectification" means including the rectification of such features regardless of the mechanism of origin.

The compositions of the invention, including their essential and optional components, are described in detail below.

Compound xanthine

The topical compositions of the present invention comprise a safe and effective amount of a variety of chemical health enhancers consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof.

Theophylline (also referred to as 7-dihydro-1,3-dimethyl-1H-purine-2,6-dione or

1,3 - dimethylxanthine) and theobromine (also referred to as

3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione or 1,3-dimethylxanthine) are commercially available from Sigma Chemical Company (St.Luis.MO); Aldrich Chemical Company (Milwaukee, WI); and Fluka Chemika-USA (Ronkonkonma, NY).

In the compositions of the present invention, the xanthine compound preferably comprises from about 0.01 wt. % to about 50 wt. % of the composition, preferably from about 0.1% to about 20%, more preferably from about 1% to about 10%, even more preferably from about 2% to about 8%, and most preferably from about 4% to about 6%.

• · • ·

Without being limited by theory, we believe that these xanthine compounds increase the rate of skin conversion, which in turn leads to a final improvement in the appearance of the skin structure, particularly the facial skin. We believe that the mechanism of action of such xanthine compounds involves an increase in cellular cyclic adenosine monophosphate (cAMP) levels, leading to the induction of secondary signaling pathways, such as increases in the formation of intracellular calcium and inositol phosphate. Finally, this leads to changes in the gene appearance of the patterns that affect cell homeostasis.

Dermatologically acceptable carrier

The topical compositions of the invention also comprise a dermatologically acceptable carrier of the xanthine compound. The term "dermatologically acceptable carrier" as used herein means that the carrier is suitable for topical application to mammalian keratin tissue, has good aesthetic properties, is compatible with the efficacy of the present invention and other ingredients and does not cause any adverse safety or toxic effects. A safe and effective amount of the carrier is from about 50% to about 99.99%, preferably from about 80% to about 99.9%, more preferably from about 90% to about 98%, and most preferably from about 90% to about 95% of the composition. . The carrier may take many different forms. For example, emulsion carriers, for example, are suitable oil-in-water, water-in-oil, water-in-oil-in-water and oil-in-water-in-silicone emulsions.

Suitable carriers include an emulsion, for example an oil-in-water emulsion or a water-in-oil emulsion (eg silicone in water or water in silicone). As will be understood by those skilled in the art, the component will primarily distribute to either the aqueous or oily phase, depending on the solubility / dispersibility of the components of the composition in the water. The xanthine compounds primarily distribute to the aqueous phase. Oil-in-water emulsions are particularly suitable.

The emulsions of the invention generally comprise a solution as described above and a lipid or oil. Lipids and oils can be derived from animals, plants or oil and can be natural or synthetic (i.e., man-made). Suitable emulsions also contain a wetting agent, for example glycerin. The emulsions will also preferably further comprise from about 1% to about 10%, more preferably from about 2% to about 5%, of an emulsifier based on the weight of the carrier. The emulsifiers may be nonionic, anionic or cationic. Suitable emulsifiers are disclosed in, for example, U.S. Patent No. 3,755,560, issued August 28, 1973 to Dickert et al .; U.S. Patent No. 4,421,769, issued December 20, 1983 to Dixonet et al .; and McCutcheides Detergents and Emulsifiers, North American edition, pp. 317-324 (1986).

• · ·

The emulsions may also contain an anti-foaming agent to minimize foaming upon application to the skin. Anti-foaming agents include high molecular weight silicones and other agents well known in the art.

Suitable water-in-silicone and oil-in-water emulsions are described in detail below. a) a water-in-silicone emulsion

The water-in-silicone emulsions comprise a continuous silicone phase and a dispersed aqueous phase.

(i) a continuous silicone phase

Suitable water-in-silicone emulsions of the present invention comprise from about 1% to about 60%, more preferably from about 5% to about 40%, more preferably from about 10% by weight. % to about 20 wt. % continuous silicone phase. The continuous silicone phase exists as an outer phase that contains or surrounds the discontinuous aqueous phase described herein below.

The continuous silicone phase comprises a polyorganosiloxane oil. A suitable water-in-silicone emulsion system is designed to provide an oxidatively stable composition for the optical retinoid. The continuous silicone phase of these suitable emulsions contains between about 50 wt. % and about 99.9 wt. % polyorganosiloxane oil and less than about 50 wt. % non-silicone oil. In a particularly preferred embodiment, the continuous silicone phase comprises at least about 50%, preferably from about 60% to about 99.9%, even more preferably from about 70% to about 99.9%, and even more preferably from about 80% by weight. % to about 99.9 wt. % of polyorganosiloxane oil and up to about 50% of non-silicone oils, preferably less than about 40%, even more preferably less than about 30%, even more preferably less than about 10%, and most preferably less than about 2 wt. %. Suitable emulsion systems provide more retinoid oxidation stability over extended periods of time than comparable water-in-oil emulsions containing lower concentrations of polyorganosiloxane oil. Concentrations of non-silicone oils in the continuous silicone phase are minimized or omitted altogether to further increase the oxidative stability of the selected retinoid in the compositions. Water-in-silicone emulsions of this type are described in U.S. Patent Application Serial No. 08 / 570,275, filed Dec. 11, 1995, in the names of Joseph Michael Zukowski, Brent William Mason, Larry Richard Robinson, and Greg Georgia Hillebrand.

The organopolysiloxane oil used in the compositions may be volatile, non-volatile or a mixture of volatile and non-volatile silicones. The term "non-volatile" used in this context refers to those silicones that are liquid under ambient conditions and have a flash point (at one atmosphere pressure) of about 100 ° C or higher. The term "volatile" used in this context refers to all other silicone oils. Suitable organopolysiloxanes may be selected from a wide variety of silicones containing a wide range of volatiles and viscosities. Examples of suitable organopolysiloxane oils include polyalkylsiloxanes, cyclic polyalkylsiloxanes and polyalkylarylsiloxanes.

Polyalkyl siloxanes useful in the compositions herein include polyalkyl siloxanes having viscosities of from about 0.5 to about 1,000,000 centistokes at 25 ° C. Such polyalkylsiloxanes may be represented by the general chemical formula R ₃ SiO [R ₂ SiO] _x SiR ₃ , where R is an alkyl group having from one to about 30 carbon atoms (preferably R is methyl or ethyl, preferably methyl; mixed groups may also be used in the same molecule) and x is an integer from 0 to about 10,000, selected to achieve the desired molecular weight, which can range up to about 10,000,000. Commercially available polyalkylsiloxanes include polydimethylsiloxanes, also known as dimethicones, examples of which include a number of Vicasil®, sold by General Electrics and Dow Corning® 200, sold by Dow Corning. Specific examples of suitable polydimethylsiloxanes include Dow Corning® 200 having a viscosity of 0.65 centistokes and a boiling point of 100 ° C, Dow Corning® 225 having a viscosity of 10 centistokes and a boiling point greater than 200 ° C, and Dow Corning® 200 having, respectively, viscosities of 50, 350 and 12 500 centistokes and boiling points greater than 200 ° C. Suitable dimethicones include those represented by the formula (CH3) 3 SiO [(CH3) 2SiO] _x [CH ₃ RSiO] y Si (CH3) 3, wherein the straight or branched chain alkyl having from two to about 30 carbon atoms axay are both a One or more, selected to achieve the desired molecular weight, which may range up to about 10,000,000. Examples of such alkyl substituted dimethicones include cetyl dimethicone and lauryldimethicone.

Cyclic polyalkylsiloxanes suitable for use in these compositions include those represented by the chemical formula [SiR 2 -O] _n , wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl) and n is an integer from about 3 to about 8, more preferably n is an integer from about 3 to about 7, and most preferably n is an integer from about 4 to about 6. When R is methyl, these are typically referred to as cyclomethicones. Commercially available cyclomethicones include Dow Corning (R) 244 liquid having a viscosity of 2.5 centistokes and a boiling point of 172 ° C, in particular comprising a cyclomethicone tetramer (ie n = 4), Dow Corning (R) 344 liquid having a viscosity of 2.5 centistokes and boiling point of 178 ° C, which in particular comprises cyclomethicone pentamer (i.e., n = 5), Dow Corning® 245 liquid having a viscosity of 4.2 centistokes and a boiling point of 205 ° C, in particular comprising a mixture of cyclomethicone tetramer and pentamer (i.e., n = 4 and 5) ) a · »» φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ · Dow Corning® 345 liquid having a viscosity of 4.5 centistokes and a temperature of 217 ° C, which in particular comprises a mixture of tetrameter, pentameter and cyclomethicone hexamer (i.e., n = 4, and 6).

Also suitable are, for example, trimethylsiloxysilicate, which is a polymeric substance corresponding to the general chemical formula [(CH ₂ ) 3 SiO 1 / 2j _x [SiO 2] y, wherein x is an integer from about 1 to about 500 and y is an integer from about 1 to about 500. Commercially available trimethylsiloxysilicate is sold as a mixture with dimethicone as Dow Corning® 593 liquid.

Also suitable for use in these compositions are dimethiconols. These compounds can be represented by the chemical formulas R3 SiO [R2 SiO] _x SiR ₂ OH and HOR2SiO [R ₂ SiO] _x SiR2OH wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl) and x is an integer from 0 to about 500, selected to achieve the desired molecular weight. Commercially available dimethiconols are typically sold as mixtures with dimethicone or cyclomethicone (eg, Dow Corning® 1401, 1402 and 1403 fluids).

Polyalkylarylsiloxanes are also suitable for use in these compositions. Particularly suitable are polymethylphenylsiloxanes having a viscosity of from about 15 to about 65 centistokes at 25 ° C.

Suitable for use herein are organopolysiloxanes selected from the group consisting of polyalkylsiloxanes, alkyl substituted dimethicones, cyclomethicones, trimethylsiloxysilicates, dimethiconols, polyalkylarylsiloxanes, and mixtures thereof. More suitable for use herein are polyalkylsiloxanes and cyclomethicones. Of the polyalkylsiloxanes, dimethicones are suitable.

As mentioned above, the continuous silicone phase may comprise one or more non-silicone oils. Suitably, the concentrations of non-silicone oils in the continuous silicone phase are minimized or completely omitted in order to further enhance the oxidative stability of selected retinoids in the compositions. Suitable non-silicone oils have a melting point of about 25 ° C or less under about one atmosphere pressure. Examples of non-silicone oils suitable for use in the continuous silicone phase are those which are well known in the chemical art of the local personal care products in the form of water-in-oil emulsions, eg petroleum oil, vegetable oils, synthetic oils, polysynthetic oils, etc.

(ii) a dispersed aqueous phase

Topical compositions of the present invention comprise from about 30% to about 90%, preferably from about 50% to about 85%, and most preferably from about 70% to about 80% of the dispersed aqueous phase.

• · · · · · · · · · · · ·

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In emulsion technology, the term "dispersed phase" is a term well known to those skilled in the art, meaning that the phase exists as small particles or droplets that are suspended and surrounded by a solid phase. The dispersed phase is also known as the internal or discontinuous phase. The dispersed aqueous phase is a dispersion of small aqueous particles or droplets suspended and surrounded by the continuous silicone phase described herein before.

The aqueous phase may be water or a combination of water and one or more water-soluble or dispersible components. Non-limiting examples of such possible ingredients include thickeners, acids, bases, salts, chalets, resins, water-soluble or dispersible alcohols and polyols, buffers, stabilizers, sunscreen, colorants and the like.

Topical compositions of the invention will typically contain from about 25% to about 90%, preferably from about 40% to about 80%, and more preferably from about 60% to about 80% by weight of water in the dispersed aqueous phase.

iii) emulsifiers for dispersing the aqueous phase

The water-in-silicone emulsions of the present invention preferably comprise an emulsifier. In a suitable embodiment, the compositions comprise from about 0.1% to about 10% emulsifier, preferably from about 0.5% to about 7.5%, most preferably from about 1% to about 5% by weight of the emulsifier. The emulsifier helps to disperse and suspend the aqueous phase with a continuous silicone phase.

A wide variety of emulsifying agents can be used herein to form a suitable water-in-silicone emulsion. Known or conventional emulsifying agents can be used in the composition provided that the selected emulsifying agent is chemically and physically compatible with the basic ingredients of the composition and provides the desired dispersion properties. Suitable emulsifiers include silicone emulsifiers, silicone-free emulsifiers, and mixtures thereof, which are well known to those skilled in the art for use in local personal care products. These emulsifiers preferably have an HLB of about 14 or less, more preferably from about 2 to about 14, and most preferably from about 4 to about 14. Emulsifiers having an HLB value outside these ranges may be used in combination with other emulsifiers to achieve an effective weight average. HLB for those combinations that fall within these ranges.

Silicone emulsifiers are suitable. A wide variety of emulsifiers are applicable here. These silicone emulsifiers are typically organically modified organopolysiloxanes, also known to those skilled in the art as silicone surfactants. Suitable silicone emulsifiers include dimethicone copolyols. These are polydimethylsiloxanes that have been modified to include polyether side chains, such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and polyether chains. Ftftft ft. Ft. Ftft ft ft. Containing moieties derived from both ethylene oxide and propylene oxide. Other examples include alkyl-modified dimethicone copolyols, eg, compounds that contain C 2 to C 30 pendant side chains. Still other suitable dimethicone copolyols include materials having various pendant cationic, anionic, amphoteric, and zwitterionic moieties.

Dimethicone copolyol emulsifiers suitable herein may be described by the following general formula:

wherein R is C 1 to C 30 straight, branched or cyclic alkyl and R ² is selected from the group consisting of

- (CH ₂ ) _n -O- (CH ₂ CHR ³ O) _m -H a

- (CH ₂ ) n O- (CH ₂ CHR ³ O) m - (CH ₂ CHR ⁴ O) o -H, wherein n is an integer from 3 to about 10; R ³ and R ⁴ are selected from the group consisting of H and a C 1 to C 6 straight or branched alkyl chain such that R ³ and R ⁴ are not simultaneously the same; and m, o, x, and y are selected such that the molecule has a total molecular weight of from about 200 to about 10,000,000, wherein m, o, x and y are independently selected from integers from 1 and greater such that m and o are not simultaneously zero and z is simultaneously selected from integers from 1 or greater. It is recognized that the positional isomers of these copolyols can be achieved. The chemical representations of the R ² moieties shown above containing the groups R ³ and R ⁴ are not intended to be limiting, but are shown to be suitable as such.

They are also suitable herein, although not strictly classified as dimethicone copolyols, silicone surfactants as depicted in the formulas in the previous paragraph, wherein R ² is:

- (CH ₂ ) _n -OR ⁵ , wherein R ⁵ is a cationic, anionic, amphoteric and zwitterionic moiety.

Non-limiting examples of dimethicone copolyols and other silicone surfactants useful herein as emulsifiers include polydimethylsiloxane polyether copolymers with pendant side chains of polyethylene oxide, copolymers of polydimethylsiloxanpolyether pendant with side chains 9 9 9 9 9

9 9 polypropylene, polydimethylsiloxane polyether copolymers with pendant mixed side chains of polyethylene oxide and polypropylene oxide, polydimethylsiloxane polyether copolymers with pendant mixed side chains of poly (ethylene) (propylene) oxide, polydimethylsiloxane polyether copolymers with pendant sidechains organobetainu, polydimethylsiloxane polyether copolymers with pendant sidechains carboxylate, polydimethylsiloxane polyether copolymers with pendant side chains of quaternary ammonium; as well as further modifications of the previous copolymers containing pendant C 2 to C 30 alkyl straight, branched or cyclic moieties. Examples of suitable commercially available dimethicone copolyols sold by Dow Corning Corporation are Dow Corning® 190, 193, Q2-5220, 2501 Wax, 2-5324 liquid and 3225C (this newer substance is sold as a mixture with cyclomethicone). Cetyldimethicone copolyol is commercially available as a mixture of polyglyceryl-4-isostearate (a) hexyl laurate and is sold under the trade name ABIL® WE-09 (available from Goldschmidt). Cetyldimethicone copolyol is also commercially available as a mixture with hexyl laurate (a) polyglyceryl-3-oleate (a) cetyldimethicone and is sold under the trade name ABIL® WS-08 (also available from Goldschmidt). Other non-limiting examples of dimethicone copolyols also include lauryldimethicone copolyol, dimethicone acetate copolyol, dimethicone adipate copolyol, dimethiconbehenate copolyol, dimethicone butyl ether copolyol, dimethicone copolyol dimethicone, dimethicone diol copolyol, dimethicone diol copolyol, dimethicone oleate, copolyol dimethiconeoleate, copolyol dimethiconeoleate, copolyol dimethiconeoleate. See International Cosmetic Ingredient Dictionary, Fifth Edition, 1993.

Dimethicone copolyol emulsifiers useful herein are described in, for example, U.S. Patent No. 4,960,764 to Figureoa, J. et al., Issued October 2, 1990; European Patent No. EP 330,369, SanoGueira, issued August 30, 1989; G.H. Dahmset et al., "New Formulation Possibilities Offered by Silicone Copolyols," Cosmetics & Toiletries, Vol. 110, pp. 91-100, March 1995; ME. Carlotti et al., "Optimization of W / O-S Emulsions And Study Of The Quantitative Relationships Between Ester Structure And Emulsion Properties", J. Dispersion Science And Technology, 13 (3), 315-366 (1992); P. Hameyer, "Comparative Technological Investigations of Organosilicone Emulsifiers in Cosmetic Water-in-Oil Emulsion Preparations," HAPPI 28 (4), pp. 88-128 (1991); J. Smid-Korbar et al., "Efficiency and Usability of Silicone Surfactants in Emulsions", Provisional Communication International Journal of Cosmetic Science, 12, 135-139 (1990); and D.G. Krzysik et al., "A New Silicone Emulsifier For Water-in-Oil System",

Drug and Cosmetic Indutry, Vol. 146 (4), pp. 28-81 (April 1990).

Suitable silicone-free emulsifiers useful herein include various nonionic and anionic emulsifying agents, for example, sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1 to C30 fatty acid esters of C1 to C30 fatty alcohols, alkoxylated C1 to C30 fatty acid esters of C1 to C30 fatty acid esters. C30 fatty alcohols, C 1 -C 30 fatty alcohol alkoxylated ethers, C 1 -C 30 fatty acid polyglyceryl esters, C 1 -C 30 polyol esters, C 1 -C 30 polyol ethers, alkyl phosphates, polyoxyalkylene phosphate fatty acids, fatty acid amides, acyl lactyllates, soaps and mixtures thereof. Other suitable emulsifiers are described, for example, in Detergents and Emulsifiers, McCutcheon, North American edition (1986) issued by Allured Publishing Corporation; U.S. Patent No. 5,011,681 to Ciotti et al., Issued April 30, 1991; U.S. Patent No. 4,421,769, Dixon et al., Issued Dec. 20, 1983; and U.S. Pat.

755,560, Dickert et al., Issued Aug. 28, 1973.

Non-limiting examples of such silicone-free emulsifiers include: polyethylene glycol-20-sorbitan monolaurate (Polysorbate 20), polyethylene glycol-5-soya sterol, Steareth-20, Ceteareth-20, PPG-2 methylglucose ether distearate, Ceteth-10, Polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamincethyl phosphate, Polysorbate 60, glyceryl stearate, PEG-100 stearate, polyoxyethylene-20-sorbitan trioleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene-4-lauryl ether stearate stearate, polyglyceryl stearate stearate, polyglyceryl stearate stearate, PPG-2 methylglucose ether distearate, Ceteth-10, diethanolamincethyl phosphate, glyceryl stearate, PEG-100 stearate and mixtures thereof.

b) an oil-in-water emulsion

Other suitable topical carriers include oil-in-water emulsions having a continuous aqueous phase and a hydrophobic, water-insoluble phase ("oil phase") dispersed therein. Examples of suitable carriers containing oil-in-water emulsions are described in U.S. Pat.

073 371, Turner, D.J. et al., issued December 17, 1991; and U.S. Patent No. 5,073,372 to Turner, D.J. et al., issued Dec. 17, 1991. A particularly suitable oil-in-water emulsion comprising a disintegrating agent, a hydrophilic surfactant and water is described herein.

(i) an organizing agent

Suitable oil-in-water emulsions contain a disintegrating agent to assist in the formation of a liquid crystalline gel network structure. Without wishing to be limited by theory, we believe that the organizing agent helps to provide rheological

9 99 9 99

I 9 9

9

The properties of the composition contribute to the stability of the composition. The organizing agent may also act as an emulsifier or wetting agent. Suitable compositions of the invention comprise from about 0.5% to about 20%, preferably from about 1% to about 10%, most preferably from about 1% to about 5% by weight. % structuring agent.

Suitable structuring agents of the invention are selected from the group consisting of stearic acid, palmitic acid, stearyl alcohol, behenyl alcohol, stearic acid, palmitic acid, polyethylene glycol ether of stearyl alcohol having an average of from about 1 to about 21 ethylene oxide units, polyethylene glycol ether of cetyl alcohol having an average of about 1 into about 5 units of ethylene oxide and mixtures thereof. More preferred dispensing agents of the present invention are selected from the group consisting of stearyl alcohol, cetyl alcohol, behenyl alcohol, polyethylene glycol ether of stearyl alcohol having an average of about 2 units of ethylene oxide (steareth-2), polyethylene glycol ether of stearyl alcohol having an average of about 21 units of ethylene oxide (stearethanol-21). having an average of about 2 units of ethylene oxide and mixtures thereof. Even more preferred structuring agents of the invention are selected from the group consisting of stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, steareth-2, steareth-21, and mixtures thereof.

(ii) a hydrophilic surfactant

Suitable oil-in-water emulsions comprise from about 0.05% to about 10%, preferably from about 1% to about 6%, even more preferably from about 1% to about 3%, of at least one hydrophilic surfactant that can disperse hydrophobic substances in the aqueous phase ( % by weight of the local carrier). The wetting agent must be at least sufficiently hydrophilic to disperse in water.

Suitable surfactants include any of a wide variety of known cationic, anionic, zwitterionic and amphoteric surfactants. See Detergents and Emulsifiers, McCutcheon, North American edition (1986), published by Allured Publishing Corporation;

U.S. Patent No. 5,011,681; U.S. Patent No. 4,421,769; and US Patent No. 3,755,560.

The desired wetting agents selected will depend on the pH of the composition and the other ingredients present.

Suitable cationic surfactants, especially the quaternary ammonium dialkyl compounds, examples of which are described in U.S. Patent No. 5,151,209; U.S. Pat.

151 210; U.S. Patent No. 5,120,532; U.S. Patent No. 4,387,090; U.S. Patent No. 3,155,591; U.S. Patent No. 3,929,678; U.S. Patent No. 3,959,461; Detergents and Emulsifiers, McCutcheon, North American Edition (1979), M.C. Publishing Co .; and Schwarz et al.,

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000 · • · 0 0 0 0 0 0 0 • 0 0 0

0 0 • 000 000

00 * 0 0 0

0 0

0 0 0 0 0

0000

Surface Active Agents, Their Chemistry and Technology, New York: Interscience Publisher, 1949; the disclosure of which is incorporated herein by reference. Suitable cationic surfactants herein include cationic ammonium salts, for example those having the formula:

í Γ

R ₁ —N — R ₃ | ^J X

R 4 wherein R 1 is an alkyl group having from 12 to 30 carbon atoms or an aromatic, aryl or alkaryl group having from about 12 to about 30 carbon atoms; R ₂ , R 3 and R 4 are independently selected from hydrogen, an alkyl group having from about 1 to about 22 carbon atoms or aromatic, aryl or alkaryl groups having from about 12 to about 22 carbon atoms; and X is any compatible anion, preferably selected from the group consisting of chloride, bromide, iodide, acetate, phosphate, nitrate, sulfate, methyl sulfate, ethyl sulfate, toluenesulfonate, lactate, citrate, glycolate and mixtures thereof. In addition, the alkyl groups R 1, R ₂ , R 3 and R ₄ may contain ester and / or ether linkages or substituents formed by hydroxy or amino groups (e.g., the alkyl groups may comprise portions of polyethylene glycol or polypropylene glycol.

More preferably, R 1 is an alkyl group having from about 12 to about 22 carbon atoms; R ₂ is selected from H or an alkyl group having from about 1 to about 22 carbon atoms; R ₃ and R ₄ are independently selected from H or an alkyl group having from about 1 to about 3 carbon atoms; and X is as previously described.

Preferably, R 1 is an alkyl group having from about 12 to about 22 carbon atoms; R ₂ , R ₃ and R ₄ are selected from H or an alkyl group having from about 1 to about 3 carbon atoms; and X is as previously described.

Otherwise, other suitable cationic emulsifiers include amino-amides wherein, in the formula above, R 1 is optionally R ₅ CONH - (CH ₂ ) _{n -} wherein R 5 is an alkyl group having from about 12 to about 22 carbon atoms and n is an integer from about 2 to about 6, preferably from about 2 to about 4, and most preferably from about 2 to about 3. Non-limiting examples of such cationic emulsifiers include stearamidopropyl PG-dimmonium chloride phosphate, behenamidopropyl PG-dimonium chloride, stearamidopropyl ethyldimonium ethosulfate, stearamidopropyl dimethyl dimethyl (meristylacetate) ammonium chloride, stearamidopropyl -dimethylcetearyl ammonium toluenesulfonate, stearamidopropyl dimethylammonium chloride, stearamidopropyl dimethylammonium lactate and mixtures thereof. Behenamidopropyl-PG-dimonium chloride is particularly suitable.

♦ 0

0 0 • 0 • 0 00 ♦ 0 • 0

0000 000

00 • · 0 0 · 0 0 • 00

0000

Nonlimiting examples of quaternary ammonium salt cationic surfactants include those selected from the group consisting of cetylamoniumchloridu, cetylamoniumbromidu, laurylamoniumchloridu, laurylamoniumbromidu, stearyl, stearylamoniumbromidu, cetyldimethylamoniumchloridu, cetyl dimethyl ammonium, dicetyl lauryldimethylamoniumbromidu, stearyldimethylamoniumchloridu, stearyldimethylamoniumbromidu, cetyltrimethylammonium chloride, cetyltrimethylammonium bromide, lauryl, lauryltrimethylamoniumbromidu, stearyltrimethylammonium chloride, stearyl, dicetyl stearyldimethylcetyl-ditallowdimethylammonium, dicetylamoniumchloridu, dicetylamoniumbromidu, dilauryl, dilauryl, distearylamoniumchloridu, distearylamoniumbromidu, dicetylmethylamoniumchloridu, dicetylmethylamoniumbromidu, dilaurylmethylamoniumchloridu, dilauryl distearylmethylammonium chloride, distearylmethylammonium bromide and mixtures thereof. Other quaternary ammonium salts include those in which the C 12 to C 30 alkyl carbon chain is derived from a fatty acid derived from beef tallow or from a fatty acid derived from coconut oil. The term "tallow" refers to an alkyl group derived from beef tallow fatty acids (usually hydrogenated beef tallow fatty acids), which generally have mixtures of alkyl chains in the range of C ₁₆ to C 18. The term "coconut" refers to an alkyl group derived from fatty acids derived from coconut oil, which generally have mixtures of alkyl chains in the range of C12 to C14. Examples of quaternary ammonium salts derived from tallow and coconut include di-di-dimethylammonium chloride, di-di-dimethylammonium methyl sulfate, di (hydrogenated tallow) dimethylammonium chloride, di (hydrogenated tallow) dimethylammonium acetate, di-di-dipropylammonium phosphate, alkyl di-ammonium ammonium ammonium, PG-dimmonium chloride phosphate, stearamidopropyl-ethyldimoniumethosulfate, stearamidopropyl-dimethyl (myristyl acetate) ammonium chloride, stearamidopropyl-dimethyl-cetearyl-ammonium toluenesulfonate, stearamidopropyl-dimethylammonium chloride, stearamidopropyl-dimethylammonium lactate and mixtures thereof. An example of a quaternary ammonium compound having an alkyl group having an alkyl group of < RTI ID = 0.0 > 9 9 < / RTI > The ester bond is a diglyceride (having beef tallow fatty acids) oxyethyldimethylammonium chloride.

Preferable cationic surfactants are those selected from the group consisting of behenamidopropyl PG dimonium chloride, dilauryl, distearyl dimethyl ammonium chloride, dipalmityl, distearyl dimethyl ammonium chloride, stearamidopropyl PG-dimoniumchloridfosfátu, stearamidopropyl ethyldiamonium-ethosulphate, stearamidopropyl dimethyl (myristyl acetate) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium toluenesulfonate, stearamidopropyl dimethylammonium chloride, stearamidopropyl dimethylammonium lactate and mixtures thereof.

Preferred cationic surfactants are those selected from the group consisting of behenamidopropyl-PG-dimmonium chloride, dilauryldimethylammonium chloride, distearyldimethylammonium chloride, dimyristyldimethylammonium chloride, dipalmityldimethylammonium chloride, and mixtures thereof.

A suitable combination of a cationic surfactant and a structuring agent is behenamidopropyl-PG-dimmonium chloride and / or behenyl alcohol, wherein the ratio is best optimized to promote or enhance physical and chemical stability, especially when such a combination contains ionic and / or highly polar solvents. This combination is particularly suitable for the delivery of substances that protect against UV radiation, for example zinc oxide and octyl methoxycinnamate.

A large number of anionic surfactants are also suitable. See, eg, US Patent No. 3,929,678, Laughlin et al., Issued Dec. 30, 1975, which is incorporated herein by reference in its entirety. Non-limiting examples of anionic surfactants include alkoyl isethionates and alkyl and alkyl ether sulfates. Alkoyl isethionates typically have the formula RCO-OCH 2 CH 2 SO 3 M, wherein R is an alkyl or alkenyl of from about 10 to about 30 carbon atoms and M is a water-soluble cation such as ammonium, sodium, potassium and triethanolamine. Non-limiting examples of such isethionates include those alkoyl isethionates which are selected from the group consisting of ammonium cocoyl isethionate, sodium cocoyl isethionate, sodium lauroyl isethionate, sodium stearoyl isethionate, and mixtures thereof. Alkyl and alkyl ether sulfates typically have the respective formulas ROSO3M and RO (C2H4O) xSC3M where R is alkyl or alkenyl of from about 10 to about 30 carbon atoms, x is from about 1 to about 10 and M is a water-soluble cation, for example ammonium , sodium, potassium and triethanolamine. Next

A suitable class of anionic surfactants is the water-soluble salts which are the products of organic reactions of sulfuric acid of the general formula:

R1-SO3-M

Wherein R 1 is selected from the group consisting of straight or branched chain saturated aliphatic hydrocarbon groups having from about 8 to about 24, preferably about 10 to about 16, carbon atoms; and M is a cation. Still other anionic synthetic surfactants include the class designated succinamates, olefin sulfonates having about 12 to about 24 carbon atoms, and β-alkoxyalkane sulfonates. Examples of these are sodium lauryl sulfate and ammonium lauryl sulfate.

Other suitable nonionic materials herein are soaps (i.e., alkali metal salts, e.g., sodium or potassium salts) of fatty acids typically having from about 8 to about 24 carbon atoms, more preferably from about 10 to about 20 carbon atoms. The fatty acids used in the production of soaps may be obtained from natural sources such as vegetable or animal-derived glycerides (eg palm oil, coconut oil, soybean oil, musk oil, tallow, lard, etc.). Fatty acids can also be prepared synthetically. They are fully described in more detail in US Patent No. 4,557,853, cited above.

Amphoteric and zwitterionic surfactants are also suitable herein. Examples of amphoteric and zwitterionic surfactants that may be used in the compositions of this invention are those that are widely described as derivatives of aliphatic secondary tertiary amines in which the aliphatic group may be a straight or branched chain wherein one of the aliphatic substituents contains from about 8 to about 22 carbon atoms (preferably C ₈ to C ₁₈ ) and one contains one anionic water-soluble group, e.g., a carboxy group, a sulfonate, a sulfate, a phosphate, or a phosphonate. Examples are alkyl imino acetates, and iminodialkanoates and aminoalkanoates of the formulas RN [CH2) _m CO2M] ₂ and RNH (CH2) _{m CO2} M wherein m is from 1 to 4, R is _C8 -C22 alkyl or alkenyl, and M is H, alkali metal , alkaline earth ammonium metal or alkanolammonium. Also included are imidazolinium and ammonium derivatives. Certain examples of suitable amphoteric surfactants include

Sodium 3-dodecyl aminopropionate, sodium 3-dodecyl aminopropane sulfonate,

N-alkyltaurines, for example, those prepared by reacting dodecylamine with sodium isethionate according to the teachings of U.S. Pat. U.S. Patent No. 2,658,072; N-higher alkyl aspartic acids, such as those prepared according to the teachings of US Patent No. 2,438,091; and products sold under the trade name "Miranol" and described in US Patent No. 2,528,378. Other examples of suitable amphoteric agents include phosphates, for example, coamidopropyl PG-dimmonium chloride phosphate (commercially available as Monaquat PTC, from of Mona Corp.).

Betaines are also suitable herein as amphoteric or zwitterionic surfactants. Examples of betaines include higher alkyl betaines such as coconut, dimethyl carboxymethyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl-alpha carboxymethyl betaine, cetyldimethylcarboxymethyl betaine, cetyldimethyl betaine (available as Lonzaine 16SP from Lonza Corp.), lauryl-bis- (2-hydroxyethyl) stearylmethyl-carboxymethyl 2-hydroxypropyl) -carboxymethylbetaine, oleyl-dimethyl-gamma-carboxypropylbetaine, lauryl-bis- (2-hydroxypropyl) -alpha-carboxyethylbetaine, coconut dimethylsulfopropylbetaine, stearyl-dimethylsulfopropylbetaine, lauryl-dimethylsulfoethylbetaine, lauryl-bis- (2-hydroxyethyl) - amidobetaines and amidosulfobetaines (wherein the RCONH (CH 2) 3 group is attached to the nitrogen betaine atom), oleyl betaine (available as amphoteric Velvetex OLB-50 from Henkel) and cocamidopropyl betaine (available as Velvetex BK-35 and BA-35 from Henkel).

Other suitable amphoteric or zwitterionic surfactants include sulphines and hydroxysultains such as cocamidopropylhydroxysultain (available as Mirataine CBS from Rhone-Poulenc) and alkanoyl sarcosinates corresponding to the formula

RCON (CH ₃ ) CH ₂ CH ₂ CO ₂ M, wherein R is an alkyl or alkenyl of from about 10 to about 20 carbon atoms and M is a water-soluble cation such as ammonium, sodium, potassium and trialkanolamine (e.g., triethanolamine), and a suitable example is sodium lauroyl sarcosinate.

(iii) water

Suitable oil-in-water emulsions comprise from about 25% to about 98%, preferably from about 65% to about 95%, more preferably from about 70% to about 90% by weight. % of the local carrier water.

The hydrophobic phase is dispersed in a continuous aqueous phase. The hydrophobic phase may comprise water-insoluble or partially soluble substances, for example those known in the art, including, for example, the silicones described herein for silicone in water emulsions and other oils and lipids as described above for emulsions. .

Topical compositions of the present invention, including, for example, lotions and creams, may contain a dermatologically acceptable emollient. Such compositions suitably comprise from about 2% to about 50% plasticizer. An "emollient" as used herein refers to a substance suitable for preventing or assisting from dryness, as well as 9 9> 999 999 * 9 • ♦ • * · 9 • ♦ • · • 9 ·· 999 9 to protect skin. A large number of plasticizers are known which can be used herein. Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972), contains many examples of substances useful as emollients. A suitable plasticizer is glycerin. Glycerin is suitably used in an amount of from about 0.001 to about 20%, preferably from about 0.01 to about 10%, most preferably from about 0.1 to about 5%, e.g. 3%.

Lotions and creams of the invention generally comprise a solution carrier system and one or more emollients. Lotions typically comprise from about 1% to about 20%, preferably from about 5% to about 10%, of an emollient; from about 50% to about 90%, preferably from about 60% to about 80%, water; and a xanthine compound in the amounts described above. The cream typically comprises from about 5% to about 50%, preferably from about 10% to about 20%, of an emollient; from about 45% to about 85%, preferably from about 50% to about 75%, water; and a xanthine compound in the amounts described above.

The ointments of the invention may comprise a natural carrier base of animal or vegetable oils or semi-solid hydrocarbons (fatty); absorbent ointment bases that absorb water to form emulsions; or water-soluble carriers, e.g., a water-soluble carrier solution. The ointments may further comprise a thickening agent, for example as described in Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 72-73 (1972), and / or plasticizer. For example, the ointment may contain from about 2% to about 10% of an emollient; from about 0.1% to about 2% of a thickening agent; and a xanthine compound in the amounts described above.

Compositions of the invention suitable as cleansing ("cleansing agents") are formulated with a suitable carrier, e.g. as described above, and suitably comprise, in addition to the xanthine compound in the above-described amounts, from about 1% to about 90%, preferably from about 5%. % to about 10%, a dermatologically acceptable surfactant. The surfactant is suitably selected from anionic, nonionic, zwitterionic, amphoteric and ampholytic surfactants, as well as mixtures of these surfactants. Such surfactants are well known to those skilled in the detergent art. Non-limiting examples of possible surfactants include isoceteth-20, sodium methylcocoyltaurate, sodium methyloleoyltaurate, and sodium lauryl sulfate. See U.S. Patent No. 4,800,197, Kowcz et al., Issued Jan. 24, 1989, which is incorporated herein by reference in its entirety, suitable for exemplary surfactants herein. Examples of a variety of other surfactants useful herein are described in Detergents and Emulsifiers, McCutcheon, North American edition (1986), published by Allured Publishing Corporation. The detergent compositions may optionally also contain, in an amount based on technology, other substances commonly used in the detergent compositions.

The physical form of the cleaning compositions is not critical. The compositions may, for example, be formulated as toilet soaps, liquids, shampoos, bath gels, hair conditioners, hair tonics, pastes or foams. Toilet soaps are the most suitable as it is the form of cleaning product most commonly used to wash the skin. Rinse cleaners, such as shampoos, require a delivery system appropriate to deposit sufficient levels of the active ingredients on the skin and hair. A suitable delivery system involves the use of insoluble complexes. For more complete details of such delivery systems, see U.S. Patent 4,835,148, Barford et al., Issued May 30, 1989.

The term "substrate" as used herein refers to a liquid, semi-solid or solid skin cosmetic composition which includes, for example, lotions, creams, gels, pastes, tables and the like. Typically, the substrate is applied to a large area of skin, such as a face, to provide a certain appearance. The substrates are typically used to provide a sticky base for color cosmetics such as lipstick, face rosette, powder, and the like, and tend to mask skin imperfections and provide the skin with a smooth, balanced appearance. The teachings of the present invention include a dermatologically acceptable carrier of the xanthine compound and may include conventional ingredients such as oils, colorants, pigments, emollients, fragrances, waxes, stabilizers and the like. Exemplary carriers and other such ingredients that are suitable for use herein are described, for example, in Patent Application Publication No. 08/430 961, issued April 28, 1995 in the names of Marcia L. Canter, Brian D. Hofrichter, and British GB 2 274 585-A, issued Jan. 23, 1993.

PH

Suitably, the compositions of the invention exhibit a pH of from about 4 to about 10. Preferably, the pH is from about 4.5 to 9.5, even more preferably from about 5 to 9, and most preferably from about 7 to 9. In an even more preferred embodiment, the pH is from from about 4 to about 6 or from about 8 to 10, preferably from about 5 to about 6 or from about 8 to about 9. Without being limited by theory, we believe that the pH thus determined helps the xanthine compound of these compositions to penetrate the skin, hair or nails. mammals. This penetration is due to the distribution of charges on the xanthine molecule, thereby making the penetration more accessible. Furthermore, it is possible that higher pH values allow modification of skin permeation pathways (eg, lipid distribution and protein interactions in stratum corneum), thereby allowing greater penetration of xanthine molecules.

Optional ingredients ··· * fc * • · · · • · · • fcfc fc ··· »• · · ·« •• fc «·· <· _# ** fcfc •« · • · • · • · fcfc ·· fcfc

The compositions of the invention may contain a number of other ingredients such as are commonly used in a given type of article, provided that they do not unacceptably alter the advantages of the invention. In an appropriate incorporation where the composition needs to be in contact with human skin, optional ingredients suitable for application to the skin should be suitable, i.e., when incorporated into such compositions, use in contact with human skin without undue toxicity, incompatibility , instability, allergic reactions, and the like in the context of healthy medical judgment. The CTFA Cosmetic Ingredient Handbook, Second Edition (1992) describes a large number of non-limiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry that are suitable for use in the compositions of the invention. Examples of classes of these ingredients include: abrasives, absorbents, aesthetic ingredients such as fragrances, pigments, dyes, essential oils, skin sensations, astringents, etc. (eg, clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, hornbeam essence ), anti-acne agents, anti-drying agents, anti-foaming agents, antibacterial agents (e.g., iodopropylbutylcarbamate), antioxidants, binders, biological additives, buffering agents, swelling agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, filmmakers or agents, eg, film-forming polymers and the nature of the agent (eg, icosene copolymer and vinylpyrrolidone), opacifiers, pH adjusters, propellants, reducing agents, sequestrant , skin whitening and brightening action agents (e.g., hydroquinone, kojic acid, ascorbic acid, magnesiumscorbyl phosphate, ascorbylglucosamine), skin modifying agents (e.g. moisturizing agents, including blending and absorbing agents), skin soothing and / or treating agents (e.g. panthenol and derivatives (e.g. ethylpanthenol), aloe vera, panthotenic acid and its derivatives, allantoin, bisabolol and dicalcium glycyrrhizinate), skin treating agents, thickeners and vitamins and derivatives thereof.

In any embodiment of the invention, however, the active ingredients may be suitably subdivided herein according to the benefit they provide or their desired mode of action. It has to be understood, however, that suitable active substances can in some cases provide more than one benefit or act in more than one way. The disaggregations are therefore made here for the sake of need and are not intended to limit the validity to a particular use or uses specified.

Desquamation agents 9 9 ·············

· # # * * * * * * * * * * * * * * * *

A safe and effective amount of desquamating agent may be added to the compositions of the invention, preferably from about 0.1% to about 10%, even more preferably from about 0.2% to about 5%, preferably also from about 0.5% to about 4%. wt. %. Desquamating agents enhance the skin benefits of the present invention. Desquamating agents, for example, aim to improve skin tissue (e.g., softness). One desquamation arrangement suitable for use herein comprises mercapto compounds and zwitterionic surfactants and is also described in pending application of periodical no. 08/480 632, filed June 7, 1995 in the name of Donald L. Bissett, corresponding to PCT application No. US 95 / 08 136, registered on 29.

Another desquamation arrangement suitable for use herein includes salicylic acid and zwitterionic surfactants and is also described in pending application of periodical no. 08/554 944, filed November 13, 1995, as a continuation of periodical no. 08/209. 401, filed March 9, 1994 in the name of Bissett, corresponding to PCT Application 94/12 745, filed November 4, 1994, published May 18, 1995. The Zwitterionic surfactants described in these applications are also suitable herein as desquamming agents. particularly preferred is cetyl betaine.

Anti-acne agents

The compositions of the invention may comprise a safe and effective amount of one or more anti-acne agents. Examples of suitable anti-acne agents include resorcinol, sulfur, salicylic acid, erythromycin, zinc, etc. Other examples of suitable anti-acne agents are described in more detail in US Patent No. 5,607,980, issued to McAtee et al., March 4, 1997.

Anti-wrinkle / anti-atrophy agents

The compositions of the invention may further comprise a safe and effective amount of one or more anti-wrinkle or anti-atrophy agents. Exemplary suitable anti-wrinkle / anti-atrophy agents for use herein include sulfur containing D and L amino acids and derivatives and salts thereof, especially N-acetyl derivatives, a suitable example of which is N-acetyl-L-cysteine; triols such as ethanethiol; hydroxy acids, phytic acid, lipoic acid, lisophosphatidic acid, skin peeling agents (eg, phenol and the like), vitamin B, compounds and retinoids that enhance the skin appearance benefits of the present invention.

(a) vitamin B3 compounds

The compositions of the invention may comprise a safe and effective amount of a vitamin B ₃ compound. Vitamin B ₃ compounds are particularly useful for regulating skin condition, as described in U.S. Patent Application Serial No. 08 / 834,010, as well as this pending. · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · To ·· ··· · April 11, 1997 (corresponding to International Publication WO 97/39733 A1, published October 30, 1997). When vitamin B3 compounds are present in the compositions of the invention, the compositions preferably comprise from about 0.01% to about 50%, more preferably from about 0.1% to about 10%, even more preferably from about 0.5% to about 10% and more preferably from about 1% to about 5%, preferably from about 2% to about 5% by weight. % of the vitamin B3 compound.

As used herein, "vitamin B3 compound" means a compound having the formula;

wherein R is - CONH 2 (ie niacinamide), - COOH (ie nicotinic acid) or - CH 2 OH (ie nicotinyl alcohol); derivatives thereof; and salts of any of the foregoing.

Examples of derivatives of the previous vitamin B3 compounds include nicotinic acid esters, including nicotinic acid esters that do not augment blood vessels (i.e., tocopheryl nicotinate), nicotinylamino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide.

Examples of suitable vitamin B ₃ compounds are well known in the art and are commercially available from a variety of sources, eg, Sigma Chemical Company (Milwaukee, WI).

A suitable vitamin B3 compound is nicotinamide.

Vitamin compounds may be included as substantially pure substances or as an extract obtained by appropriate physical and / or chemical isolation from natural (eg, plant) sources.

b) retinoids

The compositions of the invention may also contain, unless otherwise specified, a retinoid. "Retinoid" as used herein includes all natural and / or synthetic analogues of vitamin A or retinol-like compounds that possess the biological activity of vitamin A in the skin, as well as geometric isomers and stereoisomers of these compounds. Suitably, the retinoid is retinol, retinol esters (e.g., C 2 to C 22 alkyl esters of retino, including retinyl palmitate, retinyl acetate, retinilpropionate), retinal and / or retinoic acid (including all transretino acids and / or 13-cis-retinoic acid), preferably other retinoids than acid retinová. These compounds are well known in the art and are commercially available from a variety of sources, such as Sigma Chemical Company (St. Luis, MO) and Boeringher Mannheim (Indianapolis, IN). Other retinoids useful herein are described in U.S. Patent Nos. 4,677,120, issued June 30, 1987 to Parish et al .; No. 4,885,311, issued December 5, 1989 to Parish et al .; 5,049,584, issued September 17, 1991 to Purcell et al .;

• · · · · · · · · · · · · · · · · · · · ·

124,356, issued Jan. 23, 1992 to Purcell et al .; and Reissue 34,075, issued 22. September, 1992, Purcell et al. Other suitable retinoids are tocopheryl retinoate [retinoic tocopherol ester (trans- or cis-), adapalene {6- [3- (1-adamantyl) -4-methoxyphenyl] -2-naphthoic acid}, and tazarotene (ethyl-6- [ 2- (4,4-dimethylthiochroman-6-yl) ethynyl] nicotinate). Suitable retinoids are retinol, retinyl palmitate, retinyl acetate, retinyl propionate, retina and combinations thereof.

The retinoid may be included as a substantially pure substance or as an extract obtained by suitable physical and / or chemical isolation from natural (eg, plant) sources. The retinoid is preferably substantially pure, more preferably substantially pure.

The compositions of the invention may comprise a safe and effective amount of retinoid such that the resulting composition is safe to control the condition of keratin tissue, preferably to control visible and / or tactile discontinuities in skin tissue. The compositions suitably comprise from or about 0.005% to or about 2%, more preferably 0.01% to or about 2% of the retinoid. Retinol is preferably used in an amount of from about 0.01% to about 0.15%; retinol esters are preferably used in an amount of from about 0.01% to about 2% (eg, about 1%); retinoic acids are preferably used in an amount of from about 0.01% to about 0.25%; tocopheryl retinoate, adapalene and tazarotene are best used in an amount of from or about 0.01% to or about 2%.

Where the compositions of the invention comprise both a retinoid and a vitamin B3 compound, the retinoid is suitably used in the above amounts and the vitamin B3 compound is suitably used in an amount of from or about 0.1% to or about 10%, preferably from or about 2%. up to or about 5%.

Antioxidants / basic cleaners

The compositions of the invention may comprise a safe and effective amount of an antioxidant / base cleanser. The antioxidant / base cleanser is particularly useful as protection against UV radiation, which can cause increased peeling or tissue changes in the stratum corneum and from other environmental factors that can cause skin damage.

A safe and effective amount of an antioxidant / base cleanser may be added to the compositions of the invention, suitably from about 0.1% to about 10%, more preferably from about 1% to about 5% of the composition.

Antioxidants / essential cleaners such as ascorbic acid (vitamin C) and its salts, ascorbylesters of fatty acids, ascorbic acid derivatives (eg, magnesium ascorbyl phosphate), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other tocopherol esters, butylated hydroxybenzoic acid acids and their salts,

6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially available under the tradename Trolox®), gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts , amines (eg, Ν, Ν-diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (eg glutathione), dihydroxyfumaric acid and its salts, lycinpidolate, arginine pilolate, nordihydroguajaric acid, bioflavonoids, lysine, methionidine, proline, hyperutiline, proline, hyperoline tea extracts, grapefruit peel / kernel extracts, melanin and rosemary extracts. Suitable antioxidants / basic cleaners are selected from tocopherol sorbate and other tocopherol esters, preferably tocopherol sorbate. The use of tocopherol sorbate in topical compositions and applicability in the present invention, for example, is described in U.S. Pat.

No. 847,071, issued Jan. 11, 1994. July, 1989, Donald L. Bissett, Rodney D. Bush, and Ranjit Chatterjee.

Chelator

The compositions of the invention may also contain a safe and effective amount of a chelator or chelating agent. &Quot; Chelator &quot; or &quot; chelating agent &quot;, as used herein, means an active agent capable of removing a metal ion from the system by complexing such that the metal ion cannot readily participate in or catalyze chemical reactions. The inclusion of a chelating agent is particularly suitable as it provides protection against UV radiation, which may contribute to excessive peeling or skin tissue changes, and against other environmental factors that may cause skin damage.

A safe and effective amount of a chelating agent may be added to the compositions of the invention, suitably from about 0.1% to about 10%, preferably from about 1% to about 5% of the composition. Examples of chelating agents useful herein are disclosed in U.S. Patent No. 5,487,884, issued Jan. 30, 1996 to Bissett et al .; International Publication No. 91/16035, Bush et al., Issued 3.10.95; and International Publication No. 91/16034, Bush et al., issued October 31, 1995. Suitable chelators preferred in the compositions of the present invention are furildioxime and derivatives thereof.

Flavonoids

The compositions of the invention may optionally comprise a flavonoid compound. Flavonoids are fully described in US Patent Nos. 5,686,082 and 5,686,367. Flavonoids are described in U.S. Pat. Nos. 5,686,082 and 5,686,367.

Suitable for use in the present invention are flavanones selected from the group consisting of unsubstituted flavanones, mono-substituted flavanones and mixtures thereof; chalcones selected from the group consisting of unsubstituted chalcones, mono-substituted chalcones, di-substituted chalcones, tri-substituted chalcones, and mixtures thereof; flavones selected from the group consisting of unsubstituted flavones, mono-substituted flavones, di-substituted flavones, and mixtures thereof; one or more isoflavones; coumarins selected from the group consisting of unsubstituted coumarins, mono-substituted coumarins, di-substituted coumarins, and mixtures thereof; chromones selected from the group consisting of unsubstituted chromones, mono-substituted chromones, di-substituted chromones, and mixtures thereof; one or more dicoumarols; one or more chromanones; one or more chromanols; their isomers (eg, cis / trans isomers); and mixtures thereof. The term "substituted" as used herein means flavonoids in which one or more of the hydrogen atoms of the flavonoid has been independently exchanged for hydroxyl, C 1 -C 8 alkyl, C 1 -C 4 alkoxy, O-glycoside and the like or mixtures of these substituents.

Examples of suitable flavonoids include, for example, unsubstituted flavanones, mono-hydroxyflavanones (e.g., 2‘-hydroxyflavanone, 6-hydroxyflavanone,

7-hydroxyflavanone, etc.), mono-alkoxyflavanones (e.g., 5-methoxyflavanone,

6-methoxyflavanone, 7-methoxyflavanone, 4'-methoxyflavanone, etc.), unsubstituted chalcones (especially unsubstituted trans-chalcones), mono-hydroxychalcones (e.g., 2'-hydroxychalcone, 4'-hydroxychalcone, etc.), di-hydroxychalcones (e.g. 2 ', 4-dihydroxychalcone, 2', 4'-dihydroxychalcone, 2,2'-dihydroxychalcone, 2 ', 3-dihydroxychalcone, 2', 5'-dihydroxychalcone, etc.) and tri-hydroxychalcones (eg 2 ', 3 ', 4'-dihydroxychalcone, 4,2', 4'-dihydroxychalcone, 2,2 ', 4'-dihydroxychalcone, etc.), unsubstituted flavone,

7,2‘-dihydroxyflavone, 3‘, 4‘-dihydroxynaphthoflavone, 4‘-hydroxyflavone, 5,6-benzoflavone,

7,8-benzoflavone, unsubstituted isoflavone, daidzein (7,4‘-dihydroxyisoflavone),

5,7-dihydroxy-4'-methoxyisoflavone, soy isoflavones (mixture extracted from soy), unsubstituted coumarin, 4-hydroxycoumarin, 7-hydroxycoumarin,

6-hydroxy-4-methylcoumarin, unsubstituted chromone, 3-formylchromone,

3-formyl-6-isopropylchromone, unsubstituted dicoumarol, unsubstituted chromanone, unsubstituted chromanol and mixtures thereof.

Suitable for use herein are coumarins, unsubstituted flavanone, methoxyflavanones, unsubstituted chalcone, 2 ‘, 4-dihydroxychalcone, and mixtures thereof.

Most preferred are unsubstituted flavanone, unsubstituted chalcone (especially transisomer), and mixtures thereof.

They may be synthetic or may be obtained as extracts from natural sources (eg plants). The natural source material may also be further derivatized (eg, an ester or ether derivative prepared by subsequent extraction from a natural source). Flavonoid compounds useful herein are commercially available from a variety of sources, e.g., Indofine Chemical Company, Inc. (Somervile, New Jersey), Steraloids, Inc. (Wilton, New Hampshire) and Aldrich Chemical Company, Inc. (Milwaukee, Wisconsin).

Mixtures of the above flavonoid compounds may also be used.

The flavonoid compounds described herein are suitably present in the present invention at concentrations of from about 0.01% to about 20%, more preferably from about 0.1% to about 10%, and most preferably from about 0.5% to about 5%.

Anti-inflammatory agents

A safe and effective amount of an anti-inflammatory agent may be added to the compositions of the invention, suitably from about 0.1% to about 10%, more preferably from about 0.5% to about 5% of the composition. An anti-inflammatory agent enhances the skin appearance benefits of the invention, eg, such an agent contributes to a more uniform and acceptable skin tone or color. The exact amount of anti-inflammatory agent to be used in the compositions will depend on the particular anti-inflammatory agent used, as such agents vary greatly in efficacy.

Steroidal anti-inflammatory agents such as corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyldexamethasone, dexamethasone phosphate, beclomethasone, dipropionates, clobetasol valerate, desonide, desoxymetasone, difluoroacetate, difluorone, difluorone, difluorone, difluorone, difluorone fluklorolone, acetonide, fludrocortisone, flumetasone, flosetolone acetonide, fluosinolone acetonide, fluocininide, flucortinone butyl ester, fluocortolone, fluprednidene acetate (fluprednylidene), fluradrenolone, helcinonide, hydrocortisone acetate, hydrocortisone acetate, butrocate hydrocortisone, butyrate hydrocortisone, butyrate , fluradrenolone, fludrocortisone, diflurosone diacetate, fluradrenolone acetonide, medryson, amcinafel, amcinafid, betamethasone and the predominance of its esters, chloroprednisone, chlorprednisone acetate, clokortelon, spadcinolone, dichlorisone, diflurprednon t, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone,

prednisolone, prednisone, beclometasone, dipropionate, triamcinolone and mixtures thereof. A suitable anti-inflammatory steroid is hydrocortisone.

A second class of anti-inflammatory agents that are suitable in the compositions includes non-steroidal anti-inflammatory agents. A number of compounds included in this group are 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 can be made to standard texts, including Anti-inflammatory and Anti-Rheumatic Druha, K. S. Rainsford, Vol. I to III, CRC Press, Boca Raton, (1985) and Anti-inflammatory Agents, Chemistry and Pharmacology,

1, R. A. Scherrer et al., Academic Press, New York (1974).

Certain non-steroidal anti-inflammatory agents useful in the composition of the invention include, for example:

1) oxicams such as piroxicam, isoxicam, tenoxicam, sudoxicam and CP-14,304;

2) salicylates, for example aspirin, disalcid, benorylate, trilisate, safapryn, solprine, diflunisal and fendil;

3) acetic acid derivatives such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, thiopinac, zidometacin, acematacin, fentiazac, zomepirac, klindanac, oxepinac, felbinac and ketorolac;

4) phenamates such as mefenamic, meclofenamic, flufenamic, niflumic and tolfenamic acid;

5) propionic acid derivatives such as ibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, phenoprofen, fenbufen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, thioxaprofen, suprofen, alminoprofen and tiaprofen. and

6) pyrazoles, for example phenylbutazone, oxyfenbutazone, feprazone, azapropazone and trimethazone.

Mixtures of these non-steroidal anti-inflammatory agents as well as dermatologically acceptable salts and esters thereof may also be used. Especially suitable for topical application is, for example, etofenamate. Among the non-steroidal anti-inflammatory agents, ibuprofen, naproxen, flufenamic acid, etofenamate, aspirin, mefenamic acid, meclofenamic acid, piroxicam and felbinac are suitable; most preferred are ibuprofen, ketoprofen, etofenamate, aspirin and flufenamic acid.

Finally, so-called "natural" anti-inflammatory agents are suitable in the methods of the invention. Such agents may conveniently be obtained as an extract by appropriate physical and / or chemical isolation from natural sources (eg plants, fungi, by-products).

products of microorganisms). For example, candelilla wax, alpha-bisabolol, aloe vera, Manistha (extracted from plants of the genus Commiphora, in particular Commiphora Mukul), cola extract, chamomile extract and seaweed extract can be used.

Other anti-inflammatory agents useful herein include liquorice compounds (plant species / class Glycyrrhiza glabra), including glycyrrhetic acid, glycyrrhizic acid, and derivatives thereof (eg, salts and esters). Suitable salts of the foregoing compounds include metal and ammonium salts. Suitable esters include C ₂ to C ₂ 4 saturated or unsaturated esters of the acids, preferably C10 to C, preferably ₂ 4, more preferably C16 to _24th Certain examples of the foregoing include oil-soluble licorice extract, glycyrrhetic acid and glycyrrhizic acid alone, monoammonium glycyrrhizinate, monocalcium glycyrrhizinate, dicalcium glycyrrhizinate, 1-beta-glycyrrhetic acid, stearyl glycyrrhinin 3-stearyl glycyrrhinin glycyrrhetinate. Stearyl glycyrrhetinate is suitable.

Local anesthetics

The compositions of the invention may also contain a safe and effective amount of a local anesthetic. Examples of local anesthetic drugs include benzocaine, lidocaine, bupivacaine, chloprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyklonin, hexylcaine, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically acceptable salts thereof.

Tanning agents

The compositions of the invention may contain tanning agents. If present, the compositions may contain from about 0.1% to about 20%, preferably from about 2% to about 7%, and most preferably from about 3% to about 20% by weight. 6% dihydroxyacetone as an artificial tanning agent.

Dihydroxyacetone, also known as DHA or 1,3-dyhydroxy-2-propanone, is a white to off-white crystalline powder. This substance may be represented by the chemical formula C3H6O3 and the following chemical structure.

hoh ₂ c — c — ch ₂ oh

The compound may exist as a mixture of monomers and dimers, with the predominant dimers in the solid crystalline state. Upon heating or melting, the dimers cleave to provide monomers. Conversion of the dimeric form to the mortar form also occurs in aqueous solution. Dihydroxyacetone is also known to be more stable at acidic pH values. See The Merk Index, Tenth Edition, Introduction 3167, p. 463 (1983) and "Dihydroxyacetone for Cosmetics", E. MerkTechnical Bulletin, 03- 304 110, 319 897, 180 588.

Skin brightening agents

The compositions of the present invention may include skin brightening agents.

When used, the compositions suitably comprise from about 0.1% to about 10%, preferably from about 0.2% to about 5%, also suitably from about 0.5% to about 2% by weight. % skin brightening agent. Suitable skin brighteners include those known in the art, including koji-acid, arbutin, ascorbic acid and derivatives thereof, e.g.

magnesiumcorbylphosphate or sodiumcorbylphosphate. Skin-brightening agents suitable for use herein also include those described in pending patent application Serial No. 08 / 479,935, filed June 7, 1995 in the name of Hillebrand, corresponding to PCT Application No. US 95/07 432, filed 12. 6. 95; and in pending patent application Serial No. 08 / 390,152, filed February 24, 1995 in the names of Kalia L. Kvalnes, Mitchell A. DeLong, Barton J. Bradbury, Curtis B. Motley, and John D. Carter, corresponding to PCT application no. US 95/02 809, filed March 1, 95, published September 8, 95.

Antimicrobial and antifungal agents

The compositions of the invention may contain antimicrobial and antifungal agents. Such agents are capable of killing microbes, preventing microbial development or preventing the pathogenic action of microbes. A safe and effective amount of an antimicrobial and antifungal agent may be added to these compositions, suitably from about 0.001% to about 10%, preferably from about 0.01% to about 5%, and most preferably from about 0.05% to about 2%.

Examples of antimicrobial and antifungal agents include β-lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin, tetracycline, erythromycin, amikacin, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorobanopropanol, phenoxypropanilide, phenoxypropanilide, phenoxypropanilide, phenoxypropanilide , doxycycline, capreomycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, hexamidine, isethionate, metronidazole, pentamidine, gentamicin, kanamycin, lineomycin, methacycline, methenamine, minocycline, micromycin, neomycin, netomycin, netomycin, erythromycin, zinc erythromycin, erythromycin estolate, erythromycin stearate, amikacin sulphate, doxycycline hydrochloride, capreomycin sulphate, chlorhexidine gluconate, chlorhexidine hydrochloride, chlortetracycline hydrochloride, oxytetracycline hydrochloride, oxytetracycline hydrochloride, clytomide hydrochloride, clytomycin hydrochloride

metronidazole hydrochloride, pentamidine hydrochloride, gentamicin sulphate, sulphanamycin sulphate, lineomycin hydrochloride, methacycline hydrochloride, methenamine hippurate, methenamine mandelate, minocycline sulphate, neomycin sulphate, netimicin sulphate, paromomycin sulphate, streptomycin sulphate, streptomycin sulphate, streptomycin sulphate, streptomycin sulphate, octpirox, parachlorometaxylenol, nystatin, tolnaphthate, zinc pyrithione and clotrimazole.

Suitable examples of agents useful herein include those selected from the group consisting of salicylic acid, benzoyl peroxide, 3-hydroxybenzoic acid, glycolic acid, lactic acid, 4-hydroxybenzoic acid, acetylsalicylic acid, 2-hydroxybutanoic acid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, cis-retinoic acid, trans-retinoic acid, retinol, phytic acid, N-acetyl-L-cysteine, lipoic acid, azelaic acid, arachidonic acid, benzoyl peroxide, tetracycline, ibuprofen, sputtered, hydrocortisone, acetominophen, resorcinol , phenoxyethanol, phenoxypropanol, phenoxyisopropanol, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide, octopirox, lidocaine hydrochloride, clotimazole, miconazole, neocycin sulfate and mixtures thereof.

Substances protecting against UV radiation

Exposure to ultraviolet light can result in extensive peeling and tissue changes to the stratum corneum. Therefore, the compositions of the invention may optionally comprise a UV-protective agent. As used herein, a &quot; UV protector &quot; includes both UV protectors and physical sunblocks. Suitable UV protectors may be organic or inorganic. A large number of conventional UV-protection agents are suitable for use herein. Sagarin et al. in the Vlil chapter, pages 189 and in the book Cosmetic Science and Technology (1972) describe many suitable substances. Certain suitable UV protectants include, for example: p-aminobenzoic acid, its salts and derivatives thereof (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid); anthranilate (i.e. o-aminobenzoates; methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl and cyclohexenyl esters); salicylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl and dipropyphene glycol esters); cinnamic acid derivatives (menthyl and benzyl esters, α-phenylcinnamonitrile;

butylcinnamoylpyruvate); dihydroxycinnamic acid derivatives (umbelliferone, methyl umbelliferone, methylaceto-umbelliferone); trihydroxycinnamic acid derivatives (eskuletter, methyleskuletter, dafnetin and glucosides, esculin and daphnia); hydrocarbons (diphenylbutadiene, stilbene); dibenzalacetone and benzacetophenone; naphtholsulfonates (sodium salts

2-naphthol-3,6-disulfonic acid and 2-naphthol-6,8, -disulfonic acid); dihydroxynaphthoic acid and its salts; o- and p-hydroxybiphenyl disulfonates; coumarin derivatives (7-hydroxy, 7-methyl, 3-phenyl); diazoles (2-acetyl-3-bromoindazole, phenylbenzoxazole, methylnaphthoxazole, various arylbenzothiazolates); quinine salts (bisulfate, sulfate, chloride, oleate and tannates); quinoline derivatives (8-hydroxyquinoline salts, 2-phenylquinoline); hydroxy- and methoxy-substituted benzophenones; uric and violuric acids; tartaric acid and its derivatives (eg hexaethyl ether); (butylcarbotol) (6-propylpiperonyl) ether; hydroquinone; benzophenones (oxybenzene, sulisobenzone, dioxybenzone, benzoresorcinol, 2,2 ', 4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, octabenzone; 4-isopropyldibenzoylmethane; butylmethoxydibenzoylmethane; etocrylene; - (4'-methylbenzylidene-bornan-2-one) and 4-isopropyl-dibenzoylmethane.

Of these, 2-ethylhexyl p-methoxycinnamate (commercially available as PARSOL MCX), 4,4'-t-butylmethoxydibenzoylmethane (commercially available as PARSOL 1789), 2-hydroxy-4-methoxybenzophenone, octydimethyl- p-aminobenzoic acid, digaloyl trioleate, 2,2-dihydroxy-4-methoxybenzophenone, ethyl 4- (bis (hydroxypropyl)) aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, 2-ethylhexyl salicylate, glyceryl-p-aminobenzoate, 3,3,5-trimethylcyclohexylsalicylate, methyllanthranilate, p-dimethylaminobenzoic acid or aminobenzoate, 2-ethylhexyl-p-dimethylaminobenzoate, 2-phenylbenzimidazole-5-sulfonic acid, 2 - (p-dimethylaminophenyl) -5-sulfonobenzoxase, octocrylene, and mixtures thereof.

More preferred organic sunscreens useful in the compositions of this invention are 2-ethylhexyl p-methoxycinamate, butylmethoxydibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, 2-phenylbenzimidazole-5-sulfonic acid, octyldimethyl-p-aminobenzoic acid, octocrylene and their mixtures.

They are also particularly useful in such compositions, for example, the UV-protective agents disclosed in U.S. Patent No. 4,937,370, issued to Sabatelli on June 26, 1990, and U.S. Patent No. 4,999,186, issued by Sabatelli & Spirnak on March 12, 1991.

The UV-protection agents described therein have two different chromophore moieties in a single molecule that exhibit different absorption of the ultraviolet radiation spectrum. One of the chromophore parts absorbs predominantly in the UVB range and the other absorbs strongly in the UVA range.

Acidic esters are suitable members of this class of UV-protection agents.

4-N, N- (2-ethylhexyl) methylaminobenzoic acid 2,4-dihydroxybenzophenone; N, N-di- (2-ethylhexyl) -4-aminobenzoic acid ester with 4-hydroxydibenzoylmethane; 4-N, N- (2-ethylhexyl) methylaminobenzoic acid ester with 4-hydroxydibenzoylmethane; 4-N, N- (2-ethylhexyl) methyl-4-aminobenzoic acid ester

2-hydroxy-4- (2-hydroxyethoxy) benzophenone; an ester of an acid

4-N, N- (2-ethylhexyl) -methylaminobenzoic acid 4- (2-hydroxyethoxy) dibenzoylmethane; N, N-di- (2-ethylhexyl) -4-aminobenzoic acid ester of 2-hydroxy-4- (2-hydroxyethoxy) benzophenone; and an acid ester

N, N-di- (2-ethylhexyl) -4-aminobenzoic 4- (2-hydroxyethoxy) dibenzoylmethane and mixtures thereof.

Particularly suitable UV-protective agents include 4,4‘-butylmethoxydibenzoylmethane, 2-ethylhexyl-p-methoxycinamate, sulfonic acid phenyl benzimidazole and octorylene.

A safe and effective amount of a UV protector is used, typically from about 1% to about 20%, more typically from about 2% to about 10% of the composition. The exact amounts will vary depending on the UV protector selected and the required Sun Protection Factor (SPF).

Conditioning agents

The compositions of the present invention may comprise a conditioning agent selected from the group consisting of wetting, moisturizing or skin conditioners. Various such materials may be used and each may be present in an amount of from about 0.01% to about 20%, preferably from about 0.1% to about 10%, and most preferably from about 0.5% to about 7% by weight. These agents include, for example, guanidine; glycolic acid and glycolate salts (eg, ammonium and quaternary alkylammonium); salicylic acid; lactic acid and lactate salts (eg, ammonium and quaternary alkylammonium); aloe vera in any of its many forms (eg, aloe vera gel); polyhydroxy alcohols such as sorbitol, glycerol, hexanethriol, butanethriol, propylene glycol, butylene glycol, hexylene glycol and the like; polyethylene glycols; sugars (eg melibiosis) and starches; sugar and starch derivatives (eg, alkoxylated glucose and fucose); hyaluronic acid; monoethanolamine lactamide; monoethanolamine acetamide and mixtures thereof. Also suitable herein are the propoxylated glycerols described in U.S. Patent No. 4,976,953, Orr et al., Issued December 11, 1990.

Also suitable are various C 1 to C 30 monoesters and polyesters of sugars and derivatives. These esters are derived from a sugar or polyol moiety and one or more carboxylic acid moieties. Such ester materials are further described in U.S. Pat.

0-0 0 0 0 0 0 0 0 0 00 0000

No. 831,854, U.S. Patent No. 4,005,196 to Jandacek, issued Jan. 25, 1977; U.S. Pat.

005 195, Jandacek, issued Jan. 25, 1977; U.S. Patent No. 5,306,516, Letton et al., Issued April 26, 1994; U.S. Patent No. 5,306,515, Letton et al., Issued Apr. 26,

1994; U.S. Patent No. 5,305,514, Letton et al., Issued April 26, 1994; U.S. Pat.

797,300, Jandacek et al., Issued Jan. 10, 1989; U.S. Patent No. 3,963,699, Rizzi et al., Issued Jan. 15, 1976; U.S. Patent No. 4,518,722, Volpenhein, issued May 21, 1985; U.S. Patent No. 4,517,360, Volpenhein, issued May 21, 1985.

Thickening agents (including thickeners and gelling agents)

The compositions of the invention may comprise one or more thickeners, suitably from about 0.1% to about 5%, preferably from about 0.1% to about 3%, and most preferably from about 0.25% to about 2% by weight. % of the composition.

Non-limiting classes of thickeners include those selected from the group consisting of:

(a) carboxylic acid polymers

These polymers are crosslinked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acids and salts and esters of such acrylic acids, the crosslinking agent comprises one or more carbon-carbon double bonds and is derived from a polyhydride alcohol. Polymers useful in the present invention are more fully described in U.S. Patent No. 5,087,445 to Haffey et al., Issued Feb. 11, 1992; U.S. Patent No. 4,509,949, Huang et al., Issued April 5, 1985; U.S. Pat.

798,053, Brown, issued Jul. 2, 1957; and in the CTFA International Cosmetic Ingredient Dictionary, Fourth Edition, 1991, pages 12 and 80.

Examples of suitable commercially available carboxylic acid polymers include carbomers that are homopolymers of acrylic acid cross-linked with sucrose alkyl ethers or pentaerythritol. These carbomers are available as the Carbopol® 900 series from B.F. Goodriche (eg, Carbopol® 954). In addition, other suitable carboxylic acid polymers include copolymers of C 1 to C 30 alkyl acrylates with one or more acrylic acid, methacrylic acid monomers or one of its short chain esters (i.e., a C 1 -C 4 alcohol) wherein the crosslinking agent is sucrose allyl ether or pentaerythritol. These copolymers are known as acrylates / C10-30 cross-linked alkyl acrylate polymers and are commercially available as Carbopol® 1342, Carbopol® 1382, Permulen TR-1 and Permulen TR-2 from B.F. Goodrich. Examples of suitable carboxylic acid polymers herein, in other words, are those selected from the group consisting of carbomers, acrylates / C 1-10 cross-linked alkyl acrylate polymers, and mixtures thereof.

• fc- ··· · · fc fcfc fcfc • fc fcfcfcfc · fc fc fc ·· ♦ · fcfc · fc * · · «··· · · fc · fc · · · · · · · ··· fcfc · Fc * ·· «·

b) cross-linked polyacrylate polymers

The compositions of the invention may optionally include cross-linked polyacrylate polymers suitable as thickeners or gelling agents including both cationic and nonionic polymers, with cationic polymers generally being more suitable. Examples of suitable cross-linked nonionic polyacrylate polymers are those disclosed in U.S. Patent No. 5,100,660 to Hawe et al., Issued March 31, 1992; U.S. Patent No. 4,849,484, Heard, issued July 18, 1989; U.S. Patent No. 4,835,206, Farrar et al., Issued May 30, 1989; U.S. Patent No. 4,628,078, Glover et al., Issued Dec. 9, 1986; U.S. Patent No. 4,599,379, Flasher et al., Issued July 8, 1986; and EP 228 868, Farrar et al., issued July 15, 1987.

c) polyacrylamide polymers

The compositions of the invention may optionally comprise polyacrylamide polymers, especially nonionic polyacrylamide polymers including substituted branched or unbranched polymers. Most preferred among these polyacrylamide polymers is the nonionic polymer to which CTFA is designated polyacrylamide and isoparaffin and laureth-7, available under the trade name Sepigel 305 from Seppic Corporation (Fairfield, NJ).

Other polyacrylamide polymers useful herein include polyvalent copolymers of acrylamides and substituted acrylamides with acrylic acids and substituted acrylic acids. Commercially available examples of these multivalent copolymers include Hypan SR150H, SS500V, SS500W, SSSA100H, from Lipo Chemicals, Inc., (Patterson, NJ).

d) polysaccharides

A large amount of polysaccharides is suitable. "Polysaccharides" refer to gelling agents that contain a main chain of repeating units (ie, a hydrocarbon) of sugar. Non-limiting examples of polysaccharide gelling agents include those selected from the group consisting of cellulose, carboxymethylhydroxyethylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethylethylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose, cellulose methyl cellulose, ethyl cellulose acetate, cellulose acetate, cellulose acetate, cellulose acetate, cellulose acetate. Also suitable are alkyl-substituted celluloses. In these polymers, the hydroxy group of the cellulosic polymer is hydroxyalkylated (preferably hydroxyethylated or hydroxypropyllated) to form hydroxyalkylated cellulose, which is then further modified with a C 1-8 C 30 straight chain or branched chain alkyl group via an ether bond.

♦ 9 9- ··· ·· «9 * 9 9 • 99 99 99 9999

9999 «999 9 • 9999 999 • 99 999 99 ··· 99 9999

Typically, these polymers are straight chain or branched chain alcohols of C10 to C30 hydroxyalkyl celluloses. Examples of suitable alkyl groups herein include those selected from the group consisting of stearyl, isostearyl, lauryl, myristil, cetyl, isocetyl, cocoyl (i.e., alkyl groups derived from coconut oil alcohols), palmityl, oleyl, linileyl, linolenyl, ricinoleyl , behenyl and mixtures thereof. Among the alkyl hydroxyalkyl cellulose ethers is the substance to which CTFA is given the designation cetylhydroxyethylcellulose, which is an ether of cetyl alcohol and hydroxyethylcellulose. This substance is available under the tradename Natrosol® CS Plus from Aqualon Corporation (Wilmington, DE).

Other suitable polysaccharides include scleroglucans comprising a linear chain (1 to 3) of linked glucose units with (1 to 6) linked every three glucose units, a commercially available example of which is Clearogel ™ CS11 from Michel Mercier Products Inc. (Mountainside, N.J.).

(e) Resins

Other suitable thickeners and gelling agents include those that are primarily derived from natural sources. Non-limiting examples of such gelling resins include those selected from the group consisting of gum, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan resins, guarimide hydroxy, guarium resin, guarium resin, guarium hectorite, hyaluronic acid, hydrated silica, hydroxypropylchitosan, hydroxypropylguar, karaya resin, seaweed, acacia bean resin, natto resin, potassium alginate, potassium, propylene glycol alginate, sclerotin resin, sodium carboxymethyldextran, sodium gum carrageenan, xanthacrylate.

Suitable compositions of the invention include a thickener selected from the group consisting of carboxylic acid polymers, cross-linked polyacrylate polymers, polyacrylamide polymers, and mixtures thereof, preferably selected from the group consisting of carboxylic acid polymers, polyacrylamide polymers, and mixtures thereof.

While a large number of components may be included in the compositions of the claimed methods, the compositions are preferably retinoid-free, especially when such compositions are intended to regulate visible and / or tactical asymmetry in mammalian skin tissue. Furthermore, the compositions are preferably free of procaine, when such compositions are used to prevent or alleviate the use of the compositions. from itching. "Without" as used herein means that a compound or component cannot be detected in the compositions.

Preparation of the composition

The compositions of this invention are generally prepared by conventional methods, for example those known in the art of making topical compositions. Such methods typically involve mixing the components in one or more steps to a relatively uniform state, with or without heating, cooling, vacuum application, and the like.

Methods of regulating the condition of keratin tissue

The compositions of the invention are useful for controlling the condition of mammalian keratin tissue, especially the skin condition. Such targeting includes prophylactic and therapeutic targeting. More specifically, such methods of targeting are aimed at preventing and / or slowing the appearance of spider vessels and / or reddish spots on mammalian skin, preventing and / or slowing the appearance of swollen eyes and / or dark circles under mammalian eyes, desquamating mammalian skin, preventing and / or slowing the yellowness of the mammalian skin, preventing and / or slowing the sagging of the mammalian skin, softening and / or smoothing the lips, hair and nails of the mammal, and preventing and / or relieving itching of the mammalian skin.

Rectifying the condition of keratin tissue involves topically applying a safe and effective amount of a composition of the invention to keratin tissue of a mammal in need of treatment. The amount of composition to be applied, the frequency of application, and the duration of use will vary greatly depending on the amount of the xanthine compound and / or other components of the composition and the level of direction desired, e.g.

In a suitable embodiment, the composition is protracted applied to the skin. By &quot; prolonged topical application &quot; is meant continuing topical application of the composition for a prolonged period of life of the subject, suitably for a period of at least about one week, preferably for a period of at least about one month. months and preferably for a period of at least about one year. Although it is possible to benefit after different longest periods of use (eg one, ten or twenty years), it is preferable that the protracted application continues throughout life. To an individual. Typically, applications would be about once a day for such extensive periods, but the number of applications may vary from about one week to about three times a day or more. A variety of compositions of the invention can be used to provide assistance in the appearance and / or feel of keratin tissue. The amounts of such compositions that are typically administered are per application, in mg of composition / cm ^{2 of} skin, from about 0.1 mg / cm ² to about 10 mg / cm ² . A particularly suitable amount of application is about 1 mg / cm ² to about 2 mg / cm ² .

The rectification of the skin condition is particularly suitably accomplished by applying a composition in the form of a lotion, cream, gel, foam, emulsion, spray, conditioner, tonic, cosmetics, lipstick, base, nail polish, aftershave or the like to be left on. skin or other keratinous arrangement to provide some aesthetic, prophylactic, therapeutic or other benefit (i.e., a "retention" device). After the skin composition is applied, it is desirably left on the skin for at least about 15 minutes, preferably at least about 30 minutes, more preferably at least about 1 hour, preferably at least several hours, e.g. up to about 12 hours . Any exterior of the face, hair and / or nails can be treated, eg face, lips, under eye area, eyelids, scalp, neck, torso, arms, hands, feet, toenails, toenails, hair, eyelashes, eyebrows, etc.

Another way to ensure continuous exposure of the skin to at least a minimum amount of xanthine compound is to apply the compound by applying a patch, eg, to a face. Such a route is particularly suitable for an area of problem skin that needs more intensive treatment (eg, wrinkle area, facial area, and the like). The patch may be occlusive, semi-occlusive or non-occlusive. The composition comprising the xanthine compound may be included in the patch or may be applied to the skin prior to use of the patch. The patch may also contain other active agents, for example, chemical initiators of exothermic reactions, such as those described in PCT application WO 9 701 313, Burkett et al. Preferably, the patch is left on the skin for at least about 5 minutes, preferably at least about 15 minutes, more preferably at least about 30 minutes, even more preferably at least about 1 hour, preferably overnight in the form of a night treatment.

The compositions of the invention may be presented to a user or potential user (s) of the device together with information to inform such users that the use of the device will provide one or more benefits, including, for example, preventing and / or slowing the occurrence of spider vessels and / or reddish spots on • 4 <* · · ·

4 Mammalian skin, preventing and / or slowing the appearance of swollen eyes and / or dark circles under the eyes 4 4 4 4 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 mammals, desquamating the mammalian skin, preventing and / or slowing the yellowness of the mammalian skin, preventing and / or slowing the sagging of the mammalian skin, softening and / or smoothing the lips, hair and nails of mammals, and preventing and / or relieving itching of the mammalian skin and the like. Such information may also include instructions for use in order to achieve such advantages, e.g., including the method of steps described above. “Together with information” means that the information is either directly printed on the packaging of the product itself (including direct printing on the packaging itself or indirectly by means of a sticker or the like affixed to the packaging) or provided by other means, including, for example and / or other advertising so that the information is communicated to the consumer of the device. Thus, such information may include words, images, and the like.

DETAILED DESCRIPTION OF THE INVENTION

The following examples further describe and show embodiments within the scope of the invention.

The examples are given for the purpose of illustration only and are not to be construed as limiting the invention, since various versions thereof are possible without departing from the spirit and scope of the invention.

Example 1

The skin cream is prepared in conventional ways from the following ingredients:

Folder (CTFA label) Weight % PHASE A: Voda U.S.P. 2.00 Butylene glycol 0.25 Glydant Plus 0.10 STAGE B: Voda U.S.P. 70.55 Dinatrium EDTA 0.10 Panthenol 0.50 Glycerine 10.00 Theophylline 5.00 STAGE C: DC200 / 10cst 2.00 Arlamol E 3.00

9 ···

9 • 9 · 9

Cetyl palmitate 0.50 Cetyl alcohol 0.75 Stearyl alcohol 0.75 Brij 721 0.80 Brij 72 1.20 STAGE D: Sepigel 305 2.50

Stir the Phase A components with a suitable mixer (eg Teckmar model RW20DZM) and heat to thaw while mixing. In particular, mix the ingredients of Phase B in addition to theophilin with a suitable stirrer and heat to 70-75 ° C with stirring. Add theophylline at this temperature. Particularly mix the phase C components and heat to 70-75 ° C with stirring. At this temperature, add phase C to phase B and whisk for 5 minutes (eg using a Teckmar T50 whisk). Then add phase D and mix for 5 minutes. Allow to cool to 50 ° C and then add Phase A. Apply the facial skin to the individual in need of treatment at a dose of 2 mg / cm ² skin, once or twice daily for at least 3 to 6 months.

Example 2

The emulsion is prepared by conventional means from the following components:

Folder (CTFA label) Weight % PHASE A: Voda U.S.P. 66.80 Glycerine 7.00 Glydant Plus 0.10 Theofilin 5.00 Dinatrium EDTA 0.10 STAGE B: Erlamol E 5.00 Petroleum oil 5.00 Sefa Cottonate 2.00 Permethyl 101A 3.00 ArlacelP135 4.00 Petrolatum 2.00

· ♦ ···· · ·

In a suitable container filled with water, create phase A (water phase) as follows: gradually add the remaining ingredients while stirring and heat to 55 ° C.

In a special suitable vessel, create phase B (oil phase) by adding and mixing the ingredients of phase B. Start heating and stirring to 50 ° C.

Slowly add Phase A to Phase B while stirring and whisk for 15 minutes.

Apply the composition to the facial skin of an individual in need of treatment at a dose of 2 mg / cm ^{2 of} skin, once or twice daily for at least 3 to 6 months.

Example 3

The skin cream is prepared in conventional ways from the following ingredients:

Folder (CTFA label) Weight % PHASE A: Voda U.S.P. 2.00 Butylene glycol 0.25 Glydant Plus 0.10 STAGE B: Voda U.S.P. 70.55 Dinatrium EDTA 0.10 Panthenol 0.50 Glycerine 10.00 Theobromine 5.00 STAGE C: DC200 / 10cst 2.00 Arlamol E 3.00 Cetyl palmitate 0.50 Cetyl alcohol 0.75 Stearyl alcohol 0.75 Brij 721 0.80 Brij 72 1.20 STAGE D: Sepigel 305 2.50

Stir the Phase A components with a suitable mixer (eg Teckmar model RW20DZM) and heat to thaw while mixing. In particular, mix the ingredients of Phase B in addition to theophilin with a suitable stirrer and heat to 70-75 ° C with stirring. Add theophylline at this temperature. Particularly mix the phase C ingredients and heat to 70 to 70 ° C while stirring. · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 9999 999 99 999 99 9999 ° C. At this temperature, add phase C to phase B and whisk for 5 minutes (eg using a Teckmar T50 whisk). Then add phase D and mix for 5 minutes. Allow to cool to 50 ° C and then add Phase A. Apply the facial skin to the individual in need of treatment at a dose of 2 mg / cm ² skin, once or twice daily for at least 3 to 6 months.

Although certain embodiments of the invention have been described, it will be apparent to those skilled in the art that various changes and modifications to the subject matter of the invention may be made without departing from the spirit and scope of the invention. The appended claims are intended to cover all such modifications that are within the scope of the present invention.

Claims (10)

PATENT CLAIMS A method for controlling visible and / or tactile discontinuities in mammalian skin tissue, said method comprising the step of topically applying a safe and effective amount of a composition to a mammalian skin in need of such treatment, comprising: (a) a safe and effective amount of a tissue affecting agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and b) a dermatologically acceptable carrier of an agent affecting the tissue; wherein said composition does not contain retinoids. 2. A method of preventing and / or retarding the occurrence of spider vessels and / or reddish spots on mammalian skin, said method comprising the step of topically applying a safe and effective amount of a mammalian skin composition in need of such treatment, comprising: (a) a safe and effective amount of a spider catheter and / or red spot conditioner consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and b) a dermatologically acceptable carrier of the conditioner. 3. A method of preventing and / or slowing the appearance of dark circles and swollen eyes of a mammal, said method comprising the step of topically applying a safe and effective amount of a skin composition around the eyes of a mammal in need of such treatment, comprising: (a) a safe and effective amount of a dark-ring and / or swollen eye conditioner consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and b) a dermatologically acceptable carrier of the conditioner. 4. A method of preventing and / or retarding the yellowness of a mammalian skin, said method comprising the step of topically applying a safe and effective amount of a composition to the skin of a mammal in need of such treatment, comprising: w · · · · * * * * * * * * * * * * * * * * * * * * * (a) a safe and effective amount of a yellowish-improving agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and b) a dermatologically acceptable carrier of the conditioner. 5. A method of preventing and / or retarding the flaccidity of a mammalian skin, said method comprising the step of topically applying a safe and effective amount of a composition to the skin of a mammal in need of such treatment; (a) a safe and effective amount of a slackening agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and b) a dermatologically acceptable carrier of the conditioner. 6. A method of desquamating mammalian skin, said method comprising the step of topically applying a safe and effective amount of a composition to the skin of a mammal in need of such treatment, comprising: (a) a safe and effective amount of a desquamating agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and b) a dermatologically acceptable carrier for the desquamating agent; wherein said composition is free of L-carnitine and derivatives, lysosphingolipids and their salts and derivatives of sphingosines. 7. A method of softening and / or smoothing the lips, hair and nails of a mammal, said method comprising the step of topically applying a safe and effective amount of a composition to the lips, hair and nails of a mammal in need thereof, comprising: (a) a safe and effective amount of a softening and / or smoothing agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and b) a dermatologically acceptable softening and / or smoothing agent carrier. 8. A method of preventing and / or relieving itching of mammalian skin, said method comprising the step of topically applying a safe and effective amount of a composition to the skin of a mammal in need of such treatment, comprising: 99 9 9 9 9 9 9 9 9 9 999 999 99 999 9 * 9999 (a) a safe and effective amount of an itching agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; and b) a dermatologically acceptable carrier for an itching agent; wherein said composition is free of procaine. 9. The method of claim 1 wherein said composition additionally comprises a safe and effective amount of a skin care agent selected from the group consisting of anti-acne, anti-acne, vitamin B ₃ compounds, retinoids, antioxidants, essential cleansing agents. substances, chelators, anti-inflammatory agents, local anesthetics, tanning agents, skin brightening agents, anti-cellulite agents, flavonoids, antibacterial agents, antifungal agents, anti-UV agents, conditioners, conditioners, thickeners and combinations thereof. 10. A composition suitable for use in controlling the condition of the skin, said composition comprising: (a) a safe and effective amount of a xanthine compound selected from theophylline, theobromine and combinations thereof; (b) a safe and effective amount of niacinamide; and c) a dermatologically acceptable carrier of the xanthine compound and niacinamide.