KR20020011988A - Methods of regulating the condition of mammalian keratinous tissue - Google Patents

Abstract

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to various methods for the regulation of a mammalian keratinous tissue condition, comprising the step of topically applying a safe effective amount of a composition comprising the following to a mammalian keratinous tissue in need of said regulation: A) a safe 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 a further embodiment, the composition or modified variant thereof may comprise the control of visual and / or tactile discontinuity in mammalian skin tissue, the prevention and / or delay of the appearance of spider vessels and / or red stains on the mammalian skin, the mammalian eye Prevention and / or retardation of the appearance of dark circles and swollen eyes below, exfoliation of mammalian skin, prevention and / or retardation of bad color of mammalian skin, prevention and / or retardation of sagging of mammalian skin, lips, hair and nails of mammals Softening and / or smoothing, and prevention and / or alleviation of pruritus of mammalian skin.

Description

METHODS OF REGULATING THE CONDITION OF MAMMALIAN KERATINOUS TISSUE}

Cross Reference to Related Application

This application discloses US Provisional Patent Application Serial No. 60 / 134,660 [1999. 5.18].

Currently, there are many personal care products available to consumers that improve the health and physical appearance of the skin. Many of these products delay, minimize or even eliminate skin wrinkles and other histological changes associated with aging of the skin or environmental damage to human skin.

Mammalian keratinous tissue, particularly human skin, is subject to various injuries by exogenous and endogenous factors. Such exogenous factors include ultraviolet radiation, environmental pollution, wind, heat, infrared radiation, low humidity, strong surfactants, abrasives and the like. On the other hand, endogenous factors include chronological aging and other biochemical changes from within the skin. Whether exogenous or endogenous, these factors result in visual cues of skin damage. Typical skin damage includes uneven tissue, spider vessels or red stains, circles under the eyes, swollen eyes, bad color, sagging, lifeless skin, rough skin, hair and / or nails, and skin irritation resulting in pruritus.

Therefore, there is a need for products and methods for regulating keratinous tissue conditions such as skin, hair, and nails to cure such keratinous tissue conditions.

Applicants have discovered that topical compositions containing certain xanthine compounds can be used to provide therapeutic treatment as well as prevention of such keratinous tissue conditions. For example, Applicants believe that the composition comprises non-uniform skin tissue, spider vessels or skin stains, circles under the eyes, swollen eyes, blemishes, skin sagging, lifeless skin, and skin, hair and / or nails, It has been found useful in the treatment of rough keratinous tissues, and skin irritation causing pruritus, but not limited thereto.

Summary of the Invention

The present invention relates to a method of regulating a mammalian keratinous tissue condition, the method comprising topically applying a safe effective amount of a composition, each containing the following, to a mammalian keratinous tissue in need of said treatment:

a) a safe 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) Dermatologically acceptable carrier for the repair agent.

In a further embodiment, the composition comprises control of visual and / or tactile discontinuity in mammalian skin tissue, prevention and / or delay of the appearance of spider vessels and / or red stains on mammalian skin, dark circles under the mammal's eye and their Prevention and / or delay of the appearance of swollen eyes, exfoliation of mammalian skin, prevention and / or delay of bad color of mammalian skin, prevention and / or delay of sagging of mammalian skin, softening of mammalian lips, hair and nails, and And / or for smoothing and preventing and / or alleviating pruritus of mammalian skin.

The present invention relates to a method of regulating a keratinous tissue state of a mammal using a selected xanthine compound, comprising: a) regulating visual and / or tactile discontinuity in mammalian skin tissue b) mammalian skin Prevention and / or delay of the appearance of spider blood vessels and / or red blotchiness on the skin, c) prevention and / or delay of the appearance of dark circles and swollen eyes under the mammalian eye, d) poor skin color of the mammalian skin. Prevention and / or delay of, e) prevention and / or delay of sagging of mammalian skin, f) exfoliation of mammalian skin, g) softening and / or smoothing of mammal's lips, hair and nails, and h) prevention and / or alleviation of pruritus of mammalian skin. The methods are accomplished through topical application of a composition containing a selected xanthine compound to a keratinous tissue of a mammal in need of such treatment.

Unless otherwise specified, all percentages and ratios used herein are by weight of the total composition and all measurements are performed at 25 ° C.

The composition of the present invention may comprise, consist mainly of, or consist of not only the constituents of the present invention but also other ingredients described herein. As used herein, "consisting mainly of" means that the composition or ingredient It may contain, but only if the additional ingredients do not substantially change the basic novel properties of the claimed composition or method.

All publications mentioned herein are incorporated herein by reference in their entirety.

The term "keratin tissue" as used herein refers to a keratin-containing layer arranged as the outermost protective covering of a mammal, including but not limited to skin, hair, toenails, nails, cuticles, hoves, and the like. Name it.

As used herein, the term "topical application" means applying or spreading the composition of the invention on the surface of mammalian keratinous tissue.

As used herein, the term "dermatologically acceptable" means that the described composition or components thereof are suitable for use in contact with human keratinous tissue without excessive toxicity, immiscibility, instability, allergic reactions, and the like.

The term "safely effective amount" as used herein, within the scope of sound judgment by one of ordinary skill in the art, alone or in combination with the advantages disclosed herein, has a significant benefit, preferably a positive keratinous tissue appearance or texture. It is meant an amount of a compound or composition that is sufficient to come, but low enough to avoid serious side effects, i.e. provides a rational benefit to risk ratio.

As used herein, the term "peel, deprivation and / or increased turnover" refers to the removal of the upper layer of the stratum corneum (including the granular and granular layers). Without wishing to be bound by theory, it is believed that this advantage may be achieved by chemical or physical means of removing the layers from top to bottom. In addition, it is possible to exfoliate via biological means that drive the metabolism of the epidermal layer upwards from the base layer. It is believed that this involves not only the process of keratinocyte proliferation but also the induction of differentiation. The latter also raises the level of keratinization, ultimately reorganizing the trademark cortex, including the stratum corneum and granule layer.

As used herein, the term "sagging" refers to skin conditions such as skin loosening, loosening, etc. which occur as a result of loss, damage, alteration and / or abnormality of skin elastin.

As used herein, the terms "smoothing" and "softening" refer to altering the surface of keratinous tissue to enhance the feel.

The compositions of the present invention are useful for topical application and for regulating keratinous tissue conditions. Regulation of keratinous tissue conditions is often required due to conditions that can be induced or caused by internal and / or external factors. In particular, “skin condition control” can include loss of skin elasticity (loss and / or inactivation of functional skin elastin) such as loss of skin rebound from elastic fibrosis, sagging, deformation; Including the prevention of non-melanin skin discolorations such as circles under the eyes, stains (e.g., uneven red coloration due to rosacea), poor color (light color), capillary dilatation or discoloration caused by spider vessels , Prophylactically and / or therapeutically controlling skin conditions. As used herein, prophylactic skin condition control includes the delay, minimization and / or prevention of visual and / or tactile discontinuities of the skin. Therapeutic skin conditioning as used herein includes improving, such as reducing, minimizing and / or eliminating skin discontinuities. Skin condition control includes improving skin appearance and / or feel, especially facial skin (ie, visual and / or tactile discontinuity control in tissues of mammalian skin).

As used herein, "skin condition control" is intended to include the regulation of such signals regardless of the mechanism of origin.

The composition of the present invention, including its essential and optional ingredients, is described in detail below.

Xanthine compound

The topical compositions of the present invention contain a safe effective amount of various restorative agents consisting essentially of xanthine compounds selected from the group consisting of theophylline, theobromine and combinations thereof.

Theophylline (also referred to as 7-hydro-1,3-dimethyl-1H-purine-2,6-dione or 1,3-dimethylxanthine) and theobromine (also 3,7-dihydro-3,7-dimethyl- 1H-purine-2,6-dione) is available from Sigma Chemical Company (St. Louis, MO); Marketed by Aldrich Chemical Company (Milwaukee, WI) and Fluka Chemika-USA (Ronkonkonma, NY). In the compositions of the present invention, the xanthine compound is preferably from about 0.01% to about 50% by weight, more preferably from about 0.1% to about 20% by weight, even more preferably from about 1% to about 10 weight percent, even more preferably about 2 weight percent to about 8 weight percent, most preferably about 4 weight percent to about 6 weight percent.

Without being bound by theory, it is believed that the xanthine compound increases the metabolic rate of the epidermis resulting in an ultimate improvement in the tissue appearance of the skin, in particular facial skin. The mechanism of action of these xanthine compounds is believed to involve an increase in cellular cyclic adenosine monophosphate (cAMP) levels leading to an increase in intracellular calcium and induction of secondary signaling pathways such as inositol phosphate formation. Ultimately, this leads to alterations in gene expression patterns that affect cell homeostasis.

Dermatologically acceptable carrier

The topical compositions of the invention also contain a dermatologically acceptable carrier for the xanthine compound. As used herein, the phrase “dermatologically acceptable carrier” refers to a carrier suitable for topical application to keratinous tissue, with good aesthetics, compatible with the active agents and any other ingredients of the present invention, and with any desired That means no safety or toxicity issues. The safe effective amount of the carrier is from about 50% to about 99.99% of the composition, preferably from about 80% to about 99.9%, more preferably from about 90% to about 98%, most preferably from about 90% to about 95% .

The carrier can be in a wide variety of forms. For example, emulsion carriers, including but not limited to oil-in-water, water-in-oil, oil-in-water and oil-in-water-in-silicone emulsions, are useful herein.

Preferred carriers contain emulsions such as oil-in-water emulsions, water-in-oil emulsions and water-in-silicone emulsions (eg, silicon in water or water-in-silicone in water). As will be appreciated by those skilled in the art, a given component will mainly be partitioned into one of the water or oil phases, depending mainly on the water solubility / dispersity of the components in the composition. Xanthine compounds are mainly distributed in the aqueous phase. Oil-in-water emulsions are particularly preferred.

Emulsions according to the invention generally contain the solutions and lipids or oils described above. Lipids and oils can be derived from animals, plants or petroleum and can be natural or synthetic (ie, artificial). Preferred emulsions also contain humectants such as glycerin. The emulsion preferably further contains about 1% to about 10%, more preferably about 2% to about 5% emulsifier, based on the weight of the carrier. Emulsifiers may be nonionic, anionic or cationic. Suitable emulsifiers are described, for example, in US Pat. No. 3,755,560 (Dickert et al., Issued August 28, 1973); US Patent 4,421,769 (Dixon et al., Issued December 20, 1983); And McCutcheon's Detergents and Emulsifiers , North American Edition, pp. 317-324 (1986).

The emulsion may also contain an anti-foaming agent to minimize foaming when applied to the skin. Defoamers include high molecular weight silicone and other materials known in the art for this use.

Preferred water-in-silicone and oil-in-water emulsions are described in more detail below.

a) water-in-silicone emulsion

The water-in-silicone emulsion contains a continuous silicone phase and a dispersed aqueous phase.

(i) continuous silicon phase

Preferred water-in-silicone emulsions of the invention contain from about 1% to about 60% by weight, preferably from about 5% to about 40% by weight, more preferably from about 10% to about 20% by weight of a continuous silicone phase do. The continuous silicone phase is present as an external phase containing or surrounding the discontinuous aqueous phase described below.

The continuous silicone phase contains polyorganosiloxane oils. Preferred water-in-silicone emulsion systems are formulated to provide an oxidative stable vehicle for retinoids. The continuous silicone phase of the preferred emulsion contains from about 50% to about 99.9% by weight of organopolysiloxane oil, and less than about 50% by weight of non-silicone oil. In a particularly preferred embodiment, the continuous silicone phase is at least about 50% by weight, preferably from about 60% to about 99.9% by weight, more preferably from about 70% to about 99.9% by weight, even more preferably about 80% to about 99.9% by weight of polyorganosiloxane oil, and about 50% or less, preferably less than about 40%, more preferably less than about 30%, even more preferably about 10% by weight of the continuous silicone phase Less than%, even more preferably less than about 2 weight% of non-silicone oil. This preferred emulsion system provides greater oxidative stability to retinoids over longer periods than comparable water-in-oil emulsions containing low concentrations of polyorganosiloxane oils. To further enhance the oxidative stability of selected retinoids in the composition, the concentration of non-silicone oil in the continuous silicone phase is minimized or reduced entirely. Water-in-silicone emulsions of this type are described in co-pending US patent application Ser. No. 08 / 570,275 filed December 11, 1995 (Joseph Michael Zukowski, Brent William Mason, Larry Richard Robinson and Greg George Hillebrand).

The organopolysiloxane oils for use in the composition may be volatile, nonvolatile, or a mixture of volatile and nonvolatile silicones. As used herein, the term "nonvolatile" refers to silicone that is liquid under ambient conditions and has a flash point (under 1 atmosphere) above about 100 ° C. The term "volatile" as used herein refers to all other silicone oils. Suitable organopolysiloxanes can be selected from a variety of silicones over a wide range of volatilities and viscosities. Examples of suitable organopolysiloxane oils include polyalkylsiloxanes, cyclic polyalkylsiloxanes and polyalkylarylsiloxanes.

Polyalkylsiloxanes useful in the compositions herein include polyalkylsiloxanes having a viscosity of from about 0.5 to about 1,000,000 at 25 ° C. Such polyalkylsiloxanes are of the formula R ₃ SiO [R ₂ SiO] _x SiR ₃ , wherein R is an alkyl group having from 1 to about 30 carbon atoms (preferably R is methyl or ethyl, more preferably methyl; also mixed Can be used in the same molecule), x is an integer from 0 to about 10,000, selected to obtain a desired molecular weight that can range from more than about 10,000,000. Commercially available polyalkylsiloxanes include polydimethylsiloxane, also known as dimethicone, for example Vicasil from General Electric Company. Series, and Dow Corning of Dow Corning Corporation Sales 200 series can be mentioned. Specific examples of suitable polydimethylsiloxanes include Dow Corning having a viscosity of 0.65 centistoke and a boiling point of 100 ° C. Dow Corning with 200 fluids, viscosity of 10 centistokes and boiling point above 200 ° C Dow Corning with 225 fluids and viscosities of 50, 350 and 12,500 centistokes, respectively, and boiling points above 200 ° C 200 fluids. Suitable dimethicones include the formula (CH ₃ ) ₃ SiO [(CH ₃ ) ₂ SiO] _x [CH ₃ RSiO] _y Si (CH ₃ ) ₃ , wherein R is a straight or branched chain alkyl of 2 to about 30 carbon atoms And x and y are each an integer of 1 or more selected to obtain a desired molecular weight which may each be in the range of greater than about 10,000,000. Examples of such alkyl substituted dimethicones include cetyl dimethicone and lauryl dimethicone.

Suitable cyclic polyalkylsiloxanes for use in the composition include the formula [SiR ₂ -O] _n , wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl) and n is about And an integer of 3 to about 8, more preferably n is an integer of about 3 to about 7, and even more preferably n is an integer of about 4 to about 6. When R is methyl, these substances are usually named cyclomethicone. Commercially available cyclomethicones include Dow Corning having a viscosity of 2.5 centistokes and a boiling point of 172 ° C., mainly containing cyclomethicone tetramers (ie n = 4). Dow Corning with a viscosity of 2.5 centistokes and a boiling point of 178 ° C., containing 244 fluids, mainly cyclomethicone pentamers (ie n = 5) Dow Corning with a viscosity of 4.2 centistokes and a boiling point of 205 ° C., containing a mixture of 344 fluids, mainly cyclomethicone tetramers and pentamers (ie n = 4 and 5) Dow Corning with a viscosity of 4.5 centistokes and a boiling point of 217 ° C., containing 245 fluids, and predominantly cyclomethicone tetramers, pentamers and hexamers (ie n = 4, 5 and 6) 345 fluids.

In addition, polymerizable corresponding to the formula [(CH ₂ ) ₃ SiO _1/2 ] _x [SiO ₂ ] _y (wherein x is an integer of about 1 to about 500 and y is an integer of about 1 to about 500). Materials such as trimethylsiloxysilicate, which is a substance, are useful. Commercially available trimethylsiloxysilicates are available from Dow Corning It is sold as a mixture with dimethicone as 593 fluid.

Dimethiconol is also suitable for use in the composition. Such compounds are of the formula R ₃ SiO [R ₂ SiO] _x SiR ₂ OH and HOR ₂ SiO [R ₂ SiO] _x SiR ₂ OH, wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably Is methyl, x is an integer from 0 to about 500, selected to obtain the desired molecular weight. Commercial dimethiconols are usually sold as a mixture with dimethicone or cyclomethicone (eg Dow Corning 1401, 1402 and 1403 fluid).

Polyalkylaryl siloxanes are also suitable for use in the composition. Particularly useful are polymethylphenyl siloxanes having a viscosity of about 15 to about 65 centistokes at 25 ° C.

Organopolysiloxanes selected from polyalkylsiloxanes, alkyl substituted dimethicones, cyclomethicones, trimethylsiloxysilicates, dimethiconols, polyalkylaryl siloxanes and mixtures thereof are preferred for use herein. Polyalkylsiloxanes and cyclomethicones are more preferred for use herein. Preference is given to dimethicone in polyalkylsiloxanes.

As described above, the continuous silicone phase may contain one or more non-silicone oils. In order to further enhance the oxidative stability of the retinoid selected in the composition, the concentration of the non-silicone oil in the continuous silicone phase is preferably minimized or entirely reduced. Suitable non-silicone oils have a melting point of about 25 ° C. or less under about 1 atmosphere. Examples of non-silicone oils suitable for use on continuous silicone phases are known in the chemical arts in topical personal care products in the form of water-in-oil emulsions such as, for example, mineral oils, vegetable oils, synthetic oils, semi-synthetic oils and the like.

(ii) dispersed aqueous phase

The topical composition of the present invention contains from about 30% to about 90%, more preferably from about 50% to about 85%, even more preferably from about 70% to about 80% of the dispersed aqueous phase. In emulsion technology, the term "dispersed phase" is a term known to those skilled in the art that means that the phase is present as small particles or droplets suspended in and surrounded by the continuous phase. The dispersed phase is also known as the internal phase or discontinuous phase. The dispersed aqueous phase is a dispersion of small aqueous particles or drops suspended and enclosed in the continuous silicone phase described above.

The aqueous phase can be water or a combination of water and one or more water soluble or dispersible ingredients. Non-limiting examples of such ingredients include thickeners, acids, bases, salts, chelating agents, gums, water soluble or dispersible alcohols and polyols, buffers, preservatives, sunscreens, colorants, and the like.

Topical compositions of the present invention typically comprise from about 25% to about 90% by weight of the composition, preferably from about 40% to about 80% by weight, more preferably from about 60% to about 80% by weight of the dispersed aqueous phase. Will contain water.

(iii) emulsifiers for dispersing aqueous phases

The water-in-silicone emulsion of the present invention preferably contains an emulsifier. In a preferred embodiment, the composition contains from about 0.1% to about 10%, more preferably from about 0.5% to about 7.5%, most preferably from about 1% to about 5% by weight of the emulsifier of the composition. do. Emulsifiers help to disperse and suspend the aqueous phase in a continuous silicone phase.

Various emulsifiers can be used herein to form the desired water-in-silicone emulsions. Known or customary emulsifiers can be used in the composition as long as the selected emulsifier is chemically and physically compatible with the components of the composition of the invention and provides the desired dispersibility. Suitable emulsifiers include silicone emulsifiers, silicone-free emulsifiers, and mixtures thereof known to those skilled in the art for use in topical personal care products. Preferably the emulsifier has an HLB value of about 14 or less, more preferably about 2 to about 14, even more preferably about 4 to about 14. Emulsifiers having HLB values other than the above ranges may be used in combination with other emulsifiers to obtain an effective weight average HLB for formulations falling within the above ranges.

Silicone emulsifiers are preferred. Various silicone emulsifiers are useful herein. Such silicone emulsifiers are organically modified organopolysiloxanes, also known to those skilled in the art, usually as silicone surfactants. Useful silicone emulsifiers include dimethicone copolyols. Such materials are polyether modified to include polyether branched chains such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and polyether chains containing moieties derived from both ethylene oxide and propylene oxide. Dimethyl siloxane. Other examples include alkyl modified dimethicone copolyols, ie compounds containing C ₂ -C ₃₀ pendant branched chains. Still other useful dimethicone copolyols include materials having various cationic, anionic, amphoteric and zwitterionic pendant moieties.

Dimethicone copolyol emulsifiers useful herein can be described by the formula:

[Wherein R is C ₁ -C ₃₀ linear, branched or cyclic alkyl, R ² is

And

Wherein n is an integer from 3 to about 10; R ³ and R ⁴ are selected from the group consisting of H and C ₁ -C ₆ straight or branched chain alkyl such that R ³ and R ⁴ are not the same at the same time

It is selected from the group consisting of; m, o, x and y are chosen such that the molecule has a total molecular weight of about 200 to about 10,000,000, and that m and o are not both zero at the same time and z is independently selected from one or more integers, m, o, x and y is independently selected from an integer of 0 or more]. It is recognized that positional isomers of such copolyols can be obtained. The chemical representatives depicted above for the R ² moiety containing R ³ and R ⁴ groups are not intended to be limiting and are shown for convenience.

Although not strictly classified as dimethicone copolyol, R ² in the previous paragraph

Also useful herein are silicone surfactants depicted in structures wherein R ⁵ is a cationic, anionic, amphoteric or zwitterionic moiety.

Non-limiting examples of dimethicone copolyols and other silicone surfactants useful herein as emulsifiers include polydimethylsiloxane polyether copolymers with pendant polyethylene oxide branched chains, polydimethylsiloxane polyether copolymers with pendant polypropylene oxide branched chains. Polydimethylsiloxane polyether copolymer with copolymer, mixed pendant polyethylene oxide and polypropylene oxide branched chain, polydimethylsiloxane polyether copolymer with mixed pendant poly (ethylene) (propylene) oxide branched chain, pendant Polydimethylsiloxane polyether copolymers with organobetaine branched chain, polydimethylsiloxane polyether copolymers with pendant carboxylate branched chain, polydimethylsiloxane polyether copolymers with pendant quaternary ammonium branched chain; And also additional variants of these copolymers containing pendant C ₂ -C ₃₀ linear, branched or cyclic alkyl moieties. Examples of commercially available dimethicone copolyols sold herein by Dow Corning Corporation are Dow Corning 190, 193, Q2-5220, 2501 Wax, 2-5324 fluid and 3225 C (the latter being sold as a mixture with cyclomethicone). Cetyl dimethicone copolyol is commercially available as a mixture with polyglyceryl-4 isostearate (and) hexyl laurate and is traded ABIL Sold as WE-09 (available from Goldschmidt). Cetyl dimethicone copolyol is also commercially available as a mixture with hexyl laurate (and) polyglyceryl-3 oleate (and) cetyl dimethicone and is traded ABIL Sold as WS-08 (available from Goldschmidt). Other non-limiting examples of dimethicone copolyols include lauryl dimethicone coroliol, dimethicone copolyol acetate, dimethicone copolyol adipate, dimethicone copolyolamine, dimethicone copolyol behenate, dimethicone copolyol butyl ether , Dimethicone copolyol hydroxy stearate, dimethicone copolyol isostearate, dimethicone copolyol laurate, dimethicone copolyol methyl ether, dimethicone copolyol phosphate and dimethicone copolyol stearate. See International Cosmetic Ingredient Dictionary , 5th Edition, 1993.

Dimethicone copolyol emulsifiers useful herein include, for example, US Pat. No. 4,960,764 (Figueroa, Jr. et al., Oct. 2, 1990); European Patent EP 330,369 (SanoGueira, published August 30, 1989); GH Dahms 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-SEmulsions And Study Of The Quantitative Relationships Between Ester Structure And Emulsion Properties,” J. Dispersion Science And Technology , 13 (3), 315-336 (1992); [P. Hameyer, "Comparative Technological Investigations of Organic and 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 DG Krzysik et al., “A New Silicone Emulsifier For Water-in-Oil Systems,” Drug and Cosmetic Industry , vol. 146 (4) pp. 28-81 (April 1990).

Of the non-silicone-containing emulsifiers useful herein, and various non-ionic and anionic emulsifiers, such as esters and polyesters, alkoxylated sugar esters and sugar polyesters, C ₁ -C ₃₀ fatty alcohols of C ₁ -C ₃₀ fatty acid ester, C ₁ -C ₃₀ alkoxylated derivatives of C ₁ -C ₃₀ fatty acid esters of fatty alcohols, of C ₁ -C ₃₀ fatty alcohol alkoxylated ether, C ₁ -C ₃₀ fatty acids, polyglyceryl esters of C ₁ -C ₃₀ esters of polyols , C ₁ -C ₃₀ ethers of polyols, alkyl phosphates, polyoxyalkylene fatty acid ether phosphates, fatty acid amides, acyl lactylates, soaps and mixtures thereof. Other suitable emulsifiers are described, for example, in McCutcheon's, Detergents and Emulsifiers , North American Edition (1986), Allured Publishing Corporation; US Patent No. 5,011,681 (Ciotti et al., Issued April 30, 1991); US Patent 4,421,769 (Dixon et al., Issued December 20, 1983); And US Pat. No. 3,755,560 (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, cetea Ceteareth-20, PPG-2 methyl glucose ether distearate, Ceteth-10, polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, polysorbate 60, glyceryl Stearate, PEG-100 stearate, polyoxyethylene 20 sorbitan trioleate (polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4 isostearate , Hexyl laurate, stearet-20, ceteareth-20, PPG-2 methyl glucose ether distearate, cetet-10, diethanolamine cetyl Scan sulfate, glyceryl stearate, PEG-100 stearate, and mixture thereof.

b) oil-in-water emulsion

Other preferred topical carriers include oil-in-water emulsions having a continuous aqueous phase, and hydrophobic, water-insoluble phases (“oil phase”) dispersed therein. Examples of suitable oil-in-water emulsion carriers are described in US Pat. No. 5,073,371 (Turner, DJ et al., Issued Dec. 17, 1991) and US Pat. No. 5,073,372 (Turner, DJ et al., Dec. 17, 1991). have. Particularly preferred oil-in-water emulsions containing structuring agents, hydrophilic surfactants and water are described in detail below.

(i) structuring agents

Preferred oil-in-water emulsions contain structuring agents to assist in the formation of liquid crystalline gel network structures. Without being bound by theory, it is believed that structuring agents assist in providing rheological properties to the composition that contribute to the stability of the composition. The structurant may also act as an emulsifier or surfactant. Preferred compositions of the invention contain from about 0.5% to about 20%, more preferably from about 1% to about 10%, most preferably from about 1% to about 5% by weight of the structuring agent of the composition. do.

Preferred structuring agents of the present invention include polyethylene of stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, stearyl alcohol with an average of about 1 to about 21 ethylene oxide units. Glycol ethers, polyethylene glycol ethers of cetyl alcohol having an average of about 1 to about 5 ethylene oxide units, and mixtures thereof. More preferred structuring agents of the present invention are stearyl alcohol, cetyl alcohol, behenyl alcohol, polyethylene glycol ethers of stearyl alcohol having an average of about 2 ethylene oxide units (steare-2), an average of about 21 ethylene oxide Units are selected from polyethylene glycol alcohols of stearyl alcohols (stearet-21), polyethylene glycol ethers of cetyl alcohols having an average of about 2 ethylene oxide units, and mixtures thereof. Even more preferred structuring agents are selected from stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearet-2, stearet-21 and mixtures thereof.

(ii) hydrophilic surfactants

Preferred oil-in-water emulsions are from about 0.05% to about 10%, preferably from about 1% to about 6%, more preferably from about 1% to about 3%, at least one hydrophilic interface capable of dispersing hydrophobic material in the water phase. It contains the active agent (weight percentage of topical carrier). The surfactant should be sufficiently hydrophilic to at least disperse in water.

Suitable surfactants include various cationic, anionic, zwitterionic and amphoteric surfactants known in the art. McCutcheon's, Detergents and Emulsifiers , North American Edition (1986), published by Allured Publishing Corporation, incorporated herein by reference in its entirety; US Patent No. 5,011,681; US Patent No. 4,421,769; And US Pat. No. 3,755,560.

The exact surfactant chosen will depend on the pH of the composition and other components present.

US Patent No. 5,151,209, the description of which is incorporated herein by reference; US Patent No. 5,151,210; US Patent No. 5,120,532; US Patent 4,387,090; US Patent No. 3,155,591; US Patent No. 3,929,678; US Patent No. 3,959,461; McCutcheon's, Detergents and Emulsifiers (North American edition 1979) MC Publishing Co .; And cationic surfactants, in particular dialkyl quaternary ammonium compounds, examples of which are described in Schwartz et al., Surface Active Agents , Their Chemistry and Technology , New York: Interscience Publishers, 1949. Cationic surfactants useful herein include cationic ammonium salts such as those having the formula:

[Wherein R ₁ is an alkyl group having about 12 to about 30 carbon atoms or an aromatic, aryl or alkaryl group having about 12 to about 30 carbon atoms; R ₂ , R ₃ and R ₄ are independently selected from hydrogen, alkyl groups of about 1 to about 22 carbon atoms, or aromatic, aryl or alkaryl groups of about 12 to about 22 carbon atoms; X is preferably any selected from chloride, bromide, iodide, acetate, phosphate, nitrate, sulfate, methyl sulfate, ethyl sulfate, tosylate, lactate, citrate, glycolate and mixtures thereof Can be used in combination with anion. In addition, the alkyl groups of R ₁ , R ₂ , R ₃ and R ₄ may also contain ester and / or ether linkages, or hydroxy or amino group substituents (eg alkyl groups may contain polyethylene glycol and polypropylene glycol moieties). have).

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; X is as previously described.

Most 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; X is as previously described.

Optionally, other useful cationic surfactants include those in which 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 about 2 To about 6, more preferably about 2 to about 4, even more preferably an integer of about 2 to about 3). Non-limiting examples of such cationic emulsifiers include stearamidopropyl PG-dimonium chloride phosphate, behenamidopropyl PG dimonium chloride, stearamidopropyl ethyldimonium etosulphate, stearamidopropyl dimethyl (myristyl acetate) Ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate, stearmidopropyl dimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate and mixtures thereof. Behenamidopropyl PG dimonium chloride is particularly preferred.

Non-limiting examples of quaternary ammonium salt cationic surfactants include cetyl ammonium chloride, cetyl ammonium bromide, lauryl ammonium chloride, lauryl ammonium bromide, stearyl ammonium chloride, stearyl ammonium bromide, cetyl dimethyl ammonium chloride, cetyl dimethyl ammonium bromide, Lauryl dimethyl ammonium chloride, lauryl dimethyl ammonium bromide, stearyl dimethyl ammonium chloride, stearyl dimethyl ammonium bromide, cetyl trimethyl ammonium chloride, cetyl trimethylammonium bromide, lauryl trimethyl ammonium chloride, lauryl trimethyl ammonium bromide, stearyl trimethyl ammonium Chloride, stearyl trimethyl ammonium bromide, lauryl dimethyl ammonium chloride, stearyl dimethyl cetyl ditallow dimethyl ammonium chloride, Dicetyl ammonium chloride, dicetyl ammonium bromide, dilauryl ammonium chloride, dilauryl ammonium bromide, distearyl ammonium chloride, distearyl ammonium bromide, dicetyl methyl ammonium chloride, dicetyl methyl ammonium bromide, dilauryl methyl ammonium chloride, Dilauryl methyl ammonium bromide, distearyl methyl ammonium chloride, distearyl methyl ammonium bromide and mixtures thereof. Additional quaternary ammonium salts include those in which the C ₁₂ to C ₃₀ alkyl carbon chain is derived from tallow fatty acids or coconut fatty acids. The term “tallow” generally refers to alkyl groups derived from tallow fatty acids (usually hydrogenated tallow fatty acids) having a mixture of alkyl chains in the range of C ₁₆ to C ₁₈ . The term “coconut” generally refers to alkyl groups derived from coconut fatty acids having a mixture of alkyl chains in the range of C ₁₂ to C ₁₄ . Examples of quaternary ammonium salts derived from the tallow and coconut sources include ditallow dimethyl ammonium chloride, ditallow dimethyl ammonium methyl sulfate, di (hydrogenated tallow) dimethyl ammonium chloride, di (hydrogenated tallow) dimethyl Ammonium Acetate, Ditlow Dipropyl Ammonium Phosphate, Ditlow Dimethyl Ammonium Nitrate, Di (coconutalkyl) dimethyl Ammonium Chloride, Di (coconutalkyl) dimethylammonium Bromide, Tallow Ammonium Chloride, Coconut Ammonium Chloride, Stearamidopropyl PG- Dimonium chloride phosphate, stearamidopropyl ethyldimonium etosulphate, stearamidopropyl dimethyl (myristyl acetate) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyl dimethyl ammonium chlorine Id, stearic amino may be mentioned propyl dimethyl ammonium lactate, and their mixtures. An example of a quaternary ammonium compound having an alkyl group with an ester bond is diethayl oxyethyl dimethyl ammonium chloride.

More preferred cationic surfactants include behenamidopropyl PG dimonium chloride, dilauryl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, dimyristyl dimethyl ammonium chloride, dipalmityl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, Stearamidopropyl PG-Dimonium Chloride Phosphate, Stearamidopropyl Ethyldiammonium Ethosulfate, Stearamidopropyl Dimethyl (Mistyl Acetate) Ammonium Chloride, Stearamidopropyl Dimethyl Cetearyl Ammonium Tosylate, Stearamido Propyl dimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate and mixtures thereof.

Most preferred cationic surfactants are selected from behenamidopropyl PG dimonium chloride, dilauryl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, dimyristyl dimethyl ammonium chloride, dipalmityl dimethyl ammonium chloride and mixtures thereof.

Preferred combinations of cationic surfactants and structuring agents are behenamido, especially when the formulation contains ionic and / or highly polar solvents, the ratios of which are preferably optimized to be maintained to enhance physical and chemical stability. Propyl PG dimonium chloride and / or behenyl alcohol. This formulation is particularly useful for the transport of sunscreens such as zinc oxide and octyl methoxycinnamate.

Various anionic surfactants are also useful herein. See US Pat. No. 3,929,678 (Laughlin et al., Dec. 30, 1975), incorporated herein by reference in its entirety. Non-limiting examples of anionic surfactants include alcoholic isethionates, and alkyl and alkyl ether sulfates. Alcoyl isethionates are typically of the formula RCO-OCH ₂ CH ₂ SO ₃ M, wherein R is alkyl or alkenyl having from about 10 to about 30 carbon atoms, and M is a water soluble cation such as ammonium, sodium, potassium and triethanolamine Has Non-limiting examples of such isethionates include alcoyl isethionates selected from ammonium cocoyl isethionate, sodium cocoyl isethionate, sodium lauroyl isethionate, sodium stearoyl isethionate and mixtures thereof. Can be mentioned.

Alkyl and alkyl ether sulfates are typically the respective formulas of ROSO ₃ M and RO (C ₂ H ₄ O) _x SO ₃ M, wherein R is alkyl or alkenyl having from about 10 to about 30 carbon atoms, and x is about 1 To about 10, M is a water soluble cation such as ammonium, sodium, potassium, and triethanolamine). Another suitable class of anionic surfactants are water soluble salts of organic, sulfuric acid reaction products of the formula:

[Wherein R ₁ is selected from the group comprising straight or branched chain, saturated aliphatic hydrocarbon radicals having about 8 to about 24 carbon atoms, preferably about 10 to about 16 carbon atoms; M is a cation]. Still other anionic synthetic surfactants include the series designated succinamate, olefin sulfonates having about 12 to about 24 carbon atoms, and β-alkyloxy alkane sulfonates. Examples of such materials are sodium lauryl sulphate and ammonium lauryl sulphate.

Another anionic material useful herein is a soap (ie, alkali metal salt, eg sodium or potassium salt) of fatty acids, usually having from about 8 to about 24 carbon atoms, preferably from about 10 to about 20 carbon atoms. Fatty acids used in soap production can be obtained from natural sources such as, for example, plant or animal derived glycerides (eg palm oil, palm oil, soybean oil, castor oil, tallow, lard and the like). Fatty acids may be synthetically prepared. Soaps are described in more detail in US Pat. No. 4,557,853.

Amphoteric and zwitterionic surfactants are also useful herein. Examples of amphoteric and zwitterionic surfactants that may be used in the compositions of the present invention are that the aliphatic radicals may be straight or branched, and one of the aliphatic substituents contains about 8 to about 22 carbon atoms (preferably C ₈ -C ₁₈ ), broadly described as derivatives of aliphatic secondary and tertiary amines, one containing an anionic water-soluble group such as carboxy, sulfonate, sulfate, phosphate or phosphonate. Examples are alkyl imino acetates, and the formulas RN [(CH ₂ ) _m CO ₂ M] ₂ and RNH (CH ₂ ) _m CO ₂ M, wherein m is 1 to 4 and R is C ₈ -C ₂₂ alkyl Or alkenyl, and M is H, alkali metal, alkaline earth metal ammonium or alkanol ammonium) iminodialkanoate and aminoalkanoate. Imidazolinium and ammonium derivatives are also included. Examples of suitable amphoteric surfactants are sodium 3-dodecyl-aminopropionate, sodium 3-dodecylaminopropane sulfonate, N-alkyltaurine, such as according to the description of US Pat. No. 2,658,072, incorporated herein by reference in its entirety. Prepared by reacting sodium isethionate with dodecylamine; N-higher alkyl aspartic acids such as prepared according to the description of US Pat. No. 2,438,091, incorporated herein by reference in its entirety; And the products disclosed in US Pat. No. 2,528,378, sold under the trade name “Miranol” and incorporated herein by reference in its entirety. Another example of a useful amphoteric surfactant is phosphate, such as coamidopropyl PG-dimonium chloride phosphate (commercially available as Monaquat PTC from Mona Corp.).

Amphoteric or zwitterionic surfactants useful herein also include betaine. Examples of betaines include higher alkyl betaines such as coco dimethyl carboxymethyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl dimethyl alphacarboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, cetyl dimethyl betaine (from Lonza Corp. Available as Lonzaine 16SP), lauryl bis- (2-hydroxyethyl) carboxymethyl betaine, stearyl bis- (2-hydroxypropyl) carboxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, la Uryl bis- (2-hydroxypropyl) alpha-carboxyethyl betaine, coco dimethyl sulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, lauryl dimethyl sulfoethyl betaine, lauryl bis- (2-hydroxyethyl ) sulfopropyl betaine, amido betaines and amido, and do Sul Phoebe others (wherein, RCONH (CH _{2) 3} radical is attached to the nitrogen atom of the betaine), oleyl betaine to (Henkel Emitter may include available as amphoteric Velvetex OLB-50), and cocamidopropyl betaine (available as Velvetex BK-35 and BA-35 from Henkel).

Other useful amphoteric and zwitterionic surfactants include sulfines and hydroxysultaines such as cocamidopropyl hydroxysultaine (available as Mirataine CBS from Rhone-Poulenc) and the formula RCON (CH ₃ ) CH ₂ CH ₂ Alkae corresponding to CO ₂ M, wherein R is alkyl or alkenyl having from about 10 to about 20 carbon atoms and M is a water soluble cation such as ammonium, sodium, potassium and trialkanolamine (eg triethanolamine) Noyl sarcosinate, and a preferred example of this is sodium lauroyl sarcosinate.

(iii) water

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

The hydrophobic phase is dispersed in the continuous aqueous phase. The hydrophobic phase can contain water insoluble or partially soluble materials known in the art, including, but not limited to, silicones described herein with reference to water-in-silicone emulsions, and other oils and lipids described above with reference to emulsions.

Topical compositions of the present invention, including but not limited to lotions and creams, may contain dermatologically acceptable emollients. The composition preferably contains about 2% to about 50% emollient. As used herein, "emollients" refer to materials useful for the protection of skin, as well as for the prevention or alleviation of drying. Various suitable softeners are known and can be used herein. Sagarin, Cosmetics, Science and Technology , 2nd edition, Vol. 1, pp. 32-43 (1972) include many examples of materials suitable as emollients. Preferred emollient is glycerin. Glycerin is preferably used in an amount of about 0.001 to about 20%, more preferably about 0.01 to about 10%, most preferably about 0.1 to about 5%, such as 3%.

Lotions and creams according to the present invention generally contain a solution carrier system and one or more emollients. The lotion is usually from about 1% to about 20%, preferably from about 5% to about 10% of an emollient; About 50% to about 90%, preferably about 60% to about 80% of water; And xanthine compounds in the amounts described above. Creams typically range from about 5% to about 50%, preferably from about 10% to about 20%; About 45% to about 85%, preferably about 50% to about 75% of water; And xanthine compounds in the amounts described above.

Ointments of the invention include simple carrier bases (oil) for animal or vegetable oils or semisolid hydrocarbons; An absorbent occlusion substrate that absorbs water to form an emulsion; Or water soluble carriers such as water soluble solution carriers. Ointments are described in Sagarin, Cosmetics, Science and Technology , 2nd Edition, Vol. 1, pp. 72-73 (1972), and may further contain a thickener, and / or an emollient. For example, the ointment may comprise about 2% to about 10% of an emollient; About 0.1% to about 2% of a thickener; And xanthine compounds in the amounts described above.

Compositions of the invention ("cleaners") useful for cleansing are formulated, for example, with a suitable carrier as described above, and preferably in addition to the amounts of xanthine compounds described above, from about 1% to about 90%, more preferably Contains from about 5% to about 10% of a dermatologically acceptable surfactant. Surfactants are suitably selected from anionic, nonionic, zwitterionic, amphoteric and ampholytic surfactants as well as mixtures of these surfactants. Such surfactants are known to those skilled in the art of detergents. Non-limiting examples of possible surfactants include isoseteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate and sodium lauryl sulfate. For examples of surfactants useful herein, see US Pat. No. 4,800,197 (Kowcz et al., January 24, 1989), incorporated herein by reference in its entirety. Examples of various additional surfactants useful herein are described in McCutcheon's Detergents and Emulsifiers , North American Edition (1986), published by Allured Publishing Corporation. Cleansing compositions may, at levels established in the art, optionally contain other materials commonly used in cleansing compositions.

The physical form of the cleansing composition is not critical. The composition can be formulated, for example, as a toilet bar, liquid, shampoo, bath gel, hair conditioner, hair tonic, paste or mousse. Rinse-off cleansing compositions, such as shampoos, require a suitable transport system to deposit sufficient levels of active agent on the skin and scalp. Preferred transport systems involve the use of insoluble complexes. For a more complete disclosure of this transport system, see US Pat. No. 4,835,148 (Barford et al., May 30, 1989).

The term "foundation" as used herein refers to liquid, semi-liquid, semi-solid or solid skin cosmetics, including but not limited to lotions, creams, gels, pastes, cakes and the like. Foundations are typically used over large areas of the skin, such as over the face, to provide a particular appearance. Foundations are commonly used to provide an adhesion base for color cosmetics such as loose, blusher, powder, and the like, and tend to hide skin defects and give the skin a smooth, uniform appearance. The foundation of the present invention contains a dermatologically acceptable carrier for the xanthine compound and may contain conventional ingredients such as oils, colorants, pigments, emollients, pharmaceuticals, waxes, stabilizers and the like. Examples of suitable carriers and other components for use herein are described, for example, in patent application serial number 08 / 430,961 filed on April 28, 1995, in Marcia L. Canter, Brain D. Barford, and Brian D. Hofrichter. , And British Patent Application GB 2274585-A, published January 23, 1993.

pH

The composition of the present invention preferably has a pH of about 4 to about 10. More preferably the pH is about 4.5 to 9.5, even more preferably about 5 to 9, most preferably about 7 to 9. In even more preferred embodiments, the pH is about 4 to about 6 or about 8 to 10, more preferably about 5 to about 6, or about 8 to about 9. Without being bound by theory, it is believed that this limited pH helps the xanthan compound of the composition penetrate into the skin, hair or nails of a mammal. This penetration is due to the charge distribution on the xanthan molecule, which makes the xanthan molecule easier to penetrate. In addition, higher pH values allow for alteration of the penetration pathway through the skin (eg, lipid distribution and protein interactions in the stratum corneum), thereby allowing more penetration of xanthine molecules.

Random ingredient

The compositions of the present invention may include various other ingredients conventionally used in the type of product provided, unless they unacceptably alter the advantages of the present invention.

In a preferred embodiment where the composition is in contact with human keratinous tissue, the additional components should be suitable for application to keratinous tissue. That is, when incorporated into the compositions, they are suitable for use in contact with human keratinous tissue within the scope of good medical judgment without excessive toxicity, immiscibility, instability, allergic reactions, and the like. The CTFA Cosmetic Ingredient Handbook , 2nd Edition (1992) describes a wide range of non-limiting cosmetic and pharmaceutical ingredients commonly used in the field of skin care, suitable for use in the compositions of the present invention. Examples of such component groups include: abrasives, absorbents, aesthetic components such as fragrances, pigments, dyes / colorants, essential oils, skin sensitisers, astringents and the like (e.g. clove oil, menthol, camphor , Eucalyptus oil, eugenol, menthyl lactate, hamamelis distillate), anti-acne, anti-solidifying agents, antifoaming agents, antimicrobial agents (eg iodopropyl butylcarbamate), antioxidants, binders, biological Additives, buffers, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, film formers or substances, for example film-forming of a composition Polymers (eg, copolymers of eicosene and vinyl pyrrolidone), clouding agents, pH adjusting agents, propellants, reducing agents, sequestrants, skin lightening and lightening agents (eg For example, hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosamine, skin-conditioning agents (eg, humectants including various and occluded), skin soothing and / or therapeutic agents (eg Panthenol and derivatives (eg, ethyl panthenol), aloe vera, pantothenic acid and derivatives thereof, allantoin, bisabolol, and dipotassium glycyrizinate), skin treatments, thickeners, and vitamins and derivatives thereof.

However, in any embodiment of the present invention, active agents useful herein can be classified by the assumed mode of benefit or action they provide. However, it is understood that the active agents useful herein may in some cases provide one or more advantages or operate in one or more modes of action. Therefore, classifications herein are made for the purpose of convenience and are not intended to limit the active agent to a particular application or listed applications.

Release agent

A safe effective amount of release agent is more preferably in the composition of the present invention from about 0.1% to about 10% by weight of the composition, even more preferably from about 0.2% to about 5% by weight, and also preferably about 0.5% by weight. To about 4% by weight. Peeling actives enhance the skin appearance benefits of the present invention. For example, peeling actives tend to improve the texture of the skin (eg, softness). One exfoliation system suitable for use herein contains a sulfhydryl compound and a zwitterionic surfactant and is described in PCT Application No. U.S. Co-pending application Ser. No. 08 / 480,632 filed June 7, 1995, corresponding to 95/08136 [Donald L. Bissett]. Another stripping system suitable for use herein contains salicylic acid and zwitterionic surfactants and corresponds to PCT Application No. 94/12745, filed November 4, 1994 and published May 18, 1995. It is described in co-pending application serial number 08 / 554,944, filed November 13, 1995, as a continuation of serial number 08 / 209,401 [Bissett], filed March 9, 1995. Zwitterionic surfactants such as those described in this application are also useful herein as release agents, with cetyl betaine being particularly preferred.

Anti-acne actives

The compositions of the present invention may contain a safe effective amount of one or more anti-acne actives. Examples of useful anti-acne actives include resorcinol, sulfur, salicylic acid, benzoyl peroxide, erythromycin, zinc and the like. Another example of a suitable anti-acne active agent is described in more detail in US Pat. No. 5,607,980, issued March 4, 1997 to McAtee et al.

Anti-wrinkle actives / anti-wrinkle actives

The compositions of the present invention may also contain a safe effective amount of one or more anti-wrinkle actives or anti-wrinkle actives. Representative anti-wrinkle / anti-wrinkle activators suitable for use in the compositions of the present invention include sulfur-containing D and L amino acids and derivatives and salts thereof, in particular N-acetyl derivatives, wherein the preferred examples are N-acetyl-L-cysteine; Thiols such as ethane thiol; Hydroxy acid, phytic acid, lipoic acid; Lysophosphatidic acid, skin dermabrasives (eg, phenol, etc.), vitamin B ₃ compounds and retinoids that enhance the skin appearance benefits of the present invention.

a) vitamin B ₃ compounds

The composition of the present invention may contain a safe effective amount of a vitamin B ₃ compound. Vitamin B ₃ compounds are as described in co-pending US application Ser. No. 08 / 834,010, filed April 11, 1997 (corresponding to international publication WO 97/39733 Al, published October 30, 1997). It is especially useful for controlling skin conditions. When the vitamin B ₃ compound is present in the composition of the present invention, the composition is preferably from about 0.01% to about 50% by weight of the composition, more preferably from about 0.1% to about 10% by weight, even more preferably about 0.5 wt% to about 10 wt%, even more preferably about 1 wt% to about 5 wt%, even more preferably about 2 wt% to about 5 wt% of the vitamin B ₃ compound.

As used herein, “vitamin B ₃ compound” is a compound of the formula: Derivatives thereof; And any of the above salts:

Wherein R is -CONH ₂ (ie niacinamide), -COOH (ie nicotinic acid) or -CH ₂ OH (ie nicotinyl alcohol).

Representative derivatives of the vitamin B ₃ compounds include nicotinic acid esters including non-vascular expanding esters of nicotinic acid (eg, tocopheryl nicotinate), nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N -Oxides and niacinamide N-oxides.

Examples of suitable vitamin B ₃ compounds are well known in the art and include many sources such as Sigma Chemical Company (St. Louis, MO); ICN Biomedicals, Inc. (Irvin, CA) and Aldrich Chemical Company (Milwaukee, WI).

Preferably, the vitamin B ₃ compound is niacinamide.

Vitamin compounds can be included as substantially pure substances, or as extracts obtained by appropriate physical and / or chemical isolation from natural (eg, plant) resources.

b) retinoids

The composition of the present invention may also contain a retinoid. As used herein, “retinoid” includes all natural and / or synthetic analogues of vitamin A or retinol compounds having the biological activity of vitamin A in the skin, as well as the geometric isomers and stereoisomers of these compounds. Retinoids are preferably retinol, retinol esters (eg, C ₂ -C ₂₂ alkyl esters of retinol including retinyl palmitate, retinyl acetate, retinyl propionate), retinal, and / or retinic acid (Both include trans-retinic acid and / or 13-cis-retinic acid), more preferably retinoids other than retinic acid. Such compounds are well known in the art and are commercially available from many sources, such as Sigma Chemical Company (St. Louis, MO), and Boerhinger Mannheim (Indianapolis, IN). Other retinoids useful herein include US Pat. No. 4,677,120 (Parish et al.), Issued June 30, 1987; 4,855,311 (Parish et al.), Issued December 5, 1989; 5,049,584 to Purcell et al., Issued September 17, 1991; 5,124,356 (Purcell et al.), Issued June 23, 1992; And 34,075 (Purcell et al.), Re-licensed September 22, 1992. Other suitable retinoids are tocopheryl-retinoate [tocopherol ester of retinoic acid (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). Preferred retinoids are retinol, retinyl palmitate, retinyl acetate, Retinyl propionate, retinal and combinations thereof.

Retinoids may be included as substantially pure substances or as extracts obtained by appropriate physical and / or chemical isolation from natural (eg plant) resources. The retinoid is preferably substantially pure and more preferably essentially pure.

The compositions of the present invention contain a safe effective amount of retinoids such that the resulting composition controls the condition of keratinous tissue, preferably the control of visual and / or tactile discontinuity of the skin, more preferably the control of traces of skin aging, even more Preferably it can be made safe and effective in the control of visual and / or tactile discontinuities in skin texture associated with skin aging. The composition preferably contains about 0.005% to about 2%, more preferably 0.01% to about 2% of the retinoid. Retinol is preferably used in an amount of about 0.01% to about 0.15%; Retinol esters are preferably used in amounts of about 0.01% to about 2% (eg, about 1%); Retinoic acid is preferably used in an amount of about 0.01% to about 0.25%; Tocopheryl-retinoate, adapalene, and tazarotene are preferably used in amounts of about 0.01% to about 2%.

When the composition of the present invention contains both a retinoid and a vitamin B ₃ compound, the retinoid is preferably used in this amount, and the vitamin B ₃ compound is preferably from about 0.1% to about 10%, more preferably about 2% To about 5%.

Antioxidant / radical remover

The composition of the present invention may comprise a safe effective amount of an antioxidant / radical scavenger. Antioxidants / radical scavengers are particularly useful for providing protection against UV radiation, which can cause increased scaling or texture changes in the stratum corneum, and other environmental factors that can cause skin damage.

A safe effective amount of antioxidant / radical scavenger may be added to the composition of the invention, preferably from about 0.1% to about 10%, more preferably from about 1% to about 5% of the composition.

Antioxidants / radical scavengers, for example ascorbic acid (vitamin C) and salts thereof, ascorbyl esters of fatty acids, ascorbic acid derivatives (for example magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbent Bait), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acid and salts thereof, 6-hydroxy-2,5,7,8-tetramethylchroman-2- Carboxylic acid (trade name Trolox) ), Gallic acid and its alkyl esters, in particular propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (ie, N, N-diethylhydroxylamine, aminoguanidine), Sulfhydryl compounds (ie, glutathione), dihydroxy fumaric acid and salts thereof, lysine pydolate, arginine pyrrolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, methionine, proline, superoxide dismuta Agents, silymarin, tea extract, grape husk / seed extract, melanin, and rosemary extract may be used. Preferred antioxidants / radical scavengers are selected from tocopherol sorbate and other esters of tocopherol, more preferably tocopherol sorbate. For example, the use of tocopherol sorbate in topical compositions applicable to the present invention is described in US Pat. No. 4,847,071 to Donald L. Bissett, Rodney D. Bush and Ranjit Chatterjee, issued July 11, 1989. have.

Chelator

The composition of the present invention may also contain a safe effective amount of a chelator or chelating agent. As used herein, "chelator" or "chelating agent" refers to an active agent that can remove metal ions from the system by forming a complex, making it impossible for the metal ions to readily act on or catalyze the chemical reaction. Including chelating agents is particularly useful to provide protection against UV radiation, which can cause excessive scaling or skin texture changes, and other environmental factors that can cause skin damage.

A safe effective amount of chelating agent may be added to the composition of the present invention, preferably from about 0.1% to about 10%, more preferably from about 1% to about 5% of the composition. Representative chelators useful herein include US Pat. No. 5,487,884 (Bissett et al.), Issued January 30, 1996; International Publication No. 91/16035 (Bush et al.) Published October 31, 1995 and International Publication No. 91/16034 (Bush et al.) Published October 31, 1995. Preferred chelators useful in the compositions of the present invention are furyldioxime, furyl monooxime, and derivatives thereof.

Flavonoids

The composition of the present invention may optionally contain a flavonoid compound. Flavonoids are widely disclosed in US Pat. Nos. 5,686,082 and 5,686,367. Flavonoids suitable for use in the present invention include flavanones selected from unsubstituted flavanones, monosubstituted flavanones, and mixtures thereof; Chalcone selected from unsubstituted chalcones, monosubstituted chalcones, di-substituted chalcones, trisubstituted chalcones, and mixtures thereof; Flavones selected from unsubstituted flavones, monosubstituted flavones, disubstituted flavones, and mixtures thereof; One or more isoflavones; Coumarins selected from unsubstituted coumarins, monosubstituted coumarins, disubstituted coumarins, and mixtures thereof; Chromones selected from unsubstituted chromones, monosubstituted chromons, disubstituted chromons, and mixtures thereof; One or more dicoumarol; One or more chromanones; One or more chromanols; Isomers thereof (eg cis / trans isomers); And mixtures thereof. As used herein, the term "substituted" means that one or more hydrogen atoms of the flavonoids are independently substituted with hydroxyl, C ₁ -C ₈ alkyl, C ₁ -C ₄ alkoxyl, O-glycoside or the like or a mixture of the above substituents Means flavonoids.

Examples of suitable flavonoids include unsubstituted flavanones, mono-hydroxy flavanones (eg, 2'-hydroxy flavanones, 6-hydroxy flavanones, 7-hydroxy flavanones, and the like), mono-alkoxyflavanes Banone (eg, 5-methoxy flavanone, 6-methoxy flavanone, 7-methoxy flavanone, 4'-methoxy flavanone, etc.), unsubstituted chalcones (especially unsubstituted trans-chalcones), Mono-hydroxy chalcones (eg 1-hydroxy chalcones, 4′-hydroxy chalcones, etc.), di-hydroxy chalcones (eg, 2 ′, 4-dihydroxy chalcones, 2 ′, 4 '-Dihydroxy chalcones, 2,2'-dihydroxy chalcones, 2', 3-dihydroxy chalcones, 2 ', 5'-dihydroxy chalcones, etc.), and tri-hydroxy chalcones (eg For example, 2 ', 3', 4'-trihydroxy chalcone, 4,2 ', 4'-trihydroxy chalcone, 2,2', 4'-trihydroxy chalcone, etc.), unsubstituted flavones, 7 , 2'-dihydroxy flavone, 3 ', 4'-dihydroxy naphthoflavone, 4'-hydroxy flavone, 5,6-benzo Labon, and 7,8-benzoflavones, unsubstituted isoflavones, dydzein (7,4'-dihydroxy isoflavones), 5,7-dihydroxy-4'-methoxy isoflavones, soy isoflavones (Mixture extracted from soybeans), unsubstituted coumarin, 4-hydroxy coumarin, 7-hydroxy coumarin, 6-hydroxy-4-methyl coumarin, unsubstituted chromone, 3-formyl chromone, 3-formyl -6-isopropyl chromone, unsubstituted dicoumarol, unsubstituted chromanone, unsubstituted chromanol, and mixtures thereof, including but not limited to.

Preferred for use herein are unsubstituted flavanones, methoxy flavanones, unsubstituted chalcones, 2 ', 4-dihydroxy chalcones, and mixtures thereof. More preferred are unsubstituted flavanones, unsubstituted chalcones (especially trans isomers), and mixtures thereof.

These may be synthetic or obtained as extracts from natural sources (eg plants). Substances from natural sources may also be derivatized (eg, ester or ether derivatives prepared after extraction from natural sources). Flavonoid compounds useful herein include a number of sources, for example Indofine Chemical Company, Inc. (Somerville, New Jersey), Steraloids, Inc. (Wilton, New Hampshire), and Aldrich Chemical Company, Inc. (Milwaukee, Wisconsin).

Mixtures of the above flavonoid compounds may be used.

The flavonoid compounds described herein are preferably present at a concentration of about 0.01% to about 20%, more preferably about 0.1% to about 10%, even more preferably about 0.5% to about 5% in the present invention.

Anti-inflammatory

A safe effective amount of anti-inflammatory agent may be added to the composition of the present invention, preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 5% of the composition. Anti-inflammatory agents enhance the skin appearance benefits of the present invention, for example such agents contribute to a more uniform and acceptable skin tone or tone. The exact amount of anti-inflammatory agent used in the composition will vary depending on the particular anti-inflammatory agent used since the anti-inflammatory agent is broad in efficacy.

Corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone phosphate, beclomethasone dipropionate, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone Acetate, dexamethasone, dichlorisone, diplosonone diacetate, diflucortolone valerate, fluadenolone, fluclolone acetonide, fludrocortisone, flumethasone pivalate, fluorinolone acetonide, fluorinolone Nf, flucortin butyl ester, fluorocortolone, fluprednidene (fluprednylidene) acetate, flulandrenonelone, halogeninide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, Cortodoxone, Flucetonide, Fludrocortisone, Diflu Lawson diacetate, fluradrenolone, fludrocortisone, difluroson diacetate, fluradrenolone acetonide, medridone, amcinofel, amcinafide, betamethasone and the balance of its esters, chloroprednisone, chlorprednisone acetate , Clocortone, Clescinolone, Dichlorisone, Diflurfredate, Fluchloroide, Flunisolide, Fluorometallon, Fluperolone, Fluprednisolone, Hydrocortisone valerate, Hydrocortisone cyclopentylpropionate Steroidal anti-inflammatory agents can be used, including but not limited to, hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate, triamcinolone, and mixtures thereof. Preferred steroidal anti-inflammatory agents to use are hydrocortisone.

The second group of anti-inflammatory agents useful in the present compositions includes nonsteroidal anti-inflammatory agents. Various compounds included in the group are well known to those skilled in the art. For detailed disclosure of the chemical structure, synthesis, and side effects of nonsteroidal anti-inflammatory drugs, see Anti-inflammatory and Anti-Rheumatic Drugs , KD Rainsford, Vol I-III, CRC Press, Boca Raton, (1985) and Anti- Standard text including inflammatory agents, Chemistry and Pharmacology , 1, RA Scherrer et al., Academic Press, New York (1974).

Certain nonsteroidal anti-inflammatory agents useful in the compositions of the present invention include, but are not limited to:

1) Oxycams such as pyloxicam, isoxicam, tenoxycam, sudoxicam, and CP-14,304;

2) salicylates, such as aspirin, dissalside, benolylate, trilysate, sapaprin, solphrine, diflunisal, and pendosal;

3) Acetic acid derivatives such as diclofenac, fenclofenac, indomethacin, sulindac, tolmethine, isoxepac, furofenac, thiopinac, dozimethacin, acematasin, pentiazac, jomepilac, clean Danak, oxepinac, felbinac, and ketorolac;

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

5) Propionic acid derivatives, for example ibuprofen, naproxen, benoxapropene, flurbiprofen, ketoprofen, fenofene, fenbufen, indopropene, pyrpropene, carpropene, oxaprozin Pranopropene, miroprofen, thioxapropene, supropene, aminopropene, and thiapropenic; And

6) pyrazoles such as phenylbutazone, oxyphenbutazone, peprazone, azapropazone, and trimetazone.

Mixtures of the non-steroidal anti-inflammatory agents as well as dermatologically acceptable salts and esters of the formulations may be used. For example, etophenamate, flufenamic acid derivatives are particularly useful for topical applications. Among the nonsteroidal anti-inflammatory agents, ibuprofen, naproxen, flufenamic acid, etophenamate, aspirin, mefenamic acid, meclofenamic acid, pyroxicam and felbinac are preferred; Ibuprofen, naproxen, ketoprofen, etofenamate, aspirin and flufenamic acid are more preferred.

Finally, so-called "natural" anti-inflammatory agents are useful in the methods of the present invention. Such formulations may be suitably obtained as extracts or may be synthetically prepared by appropriate physical and / or chemical isolation from natural sources (eg, by-products of plants, fungi, microorganisms). For example candelilla wax, bisabolol (e.g. alpha bisabolol), aloe vera, plant sterols (e.g. phytosterols), Manjistha (extracted from the genus Rubia, in particular Rubia Cordifolia ), and Guggal ( Commiphora genus, in particular from Commiphora Mukul plants), cola extract, chamomile, red clover extract, and sea whip extract can be used.

Additional anti-inflammatory agents useful herein include Licorice (Glycyrrhia glabra genus / species plants) and compounds, including glycyrrhetic acid, glycyric acid, and derivatives (eg, salts and esters) thereof. Suitable salts of these compounds include metal and ammonium salts. Suitable esters include C ₂ -C ₂₄ , preferably C ₁₀ -C ₂₄ , more preferably C ₁₆ -C ₂₄ saturated or unsaturated esters of acids. The above-mentioned embodiments include oil-soluble licorice extract, glycyric acid and glycyrrhetic acid itself, monoammonium glycyrinate, monopotassium glycyrinate, dipotassium glycyrinate, 1-beta-glycileic acid, stearyl glyce Cyretinate, and 3-stearyloxy-glycitinic acid, and disodium 3-succinyloxy-beta-glyciretinate. Stearyl glycyrrhetinate is preferred.

Local anesthetics

The compositions of the present invention may also contain a safe effective amount of a local anesthetic. Examples of local anesthetic drugs include benzocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, ethidocaine, mepivacaine, tetracaine, diclonin, hexylcaine, procaine, cocaine, ketamine, pramoxin, Phenols, and pharmaceutically acceptable salts thereof.

Tanning actives

Compositions of the present invention may contain tanning actives. If present, the composition is from about 0.1% to about 20%, more preferably from about 2% to about 7%, even more preferably from about 3% to about 6% by weight of the artificial tanning active agent of the composition It is preferable to contain dihydroxyacetone.

Dihydroxyacetone, known as DHA or 1,3-dihydroxy-2-propanone, is a white to off-white crystalline powder. The material may be represented by the formula C ₃ H ₆ O ₃ and the following chemical structure.

This compound may exist as a mixture of monomers and dimers, and the dimers are mainly in the solid crystalline state. Upon heating or melting, dimers decompose to yield monomers. The conversion to the monomer form in dimeric form also occurs in aqueous solution. Dihydroxyacetone is also known to be safer at acidic pH values. The Merck Index , 10th edition, entry 3167, p. 463 (1983), and "Dihydroxyacetone for Cosmetics", E. Merck Technical Bulletin, 03-304 110, 319 897, 180 588.

Skin lightening

The composition of the present invention may contain a skin lightening agent. When used, the composition preferably contains about 0.1% to about 10% by weight of the composition, more preferably about 0.2% to about 5% by weight of the composition, and also preferably about 0.5% to about 2% by weight of the skin. Contains a lightening agent. Suitable skin lightening agents include those known in the art, including kojic acid, arbutin, ascorbic acid and derivatives thereof such as magnesium ascorbyl phosphate or sodium ascorbyl phosphate. Skin lightening agents suitable for use herein include PCT Application U.S. Patent Application, filed June 12, 1995. Co-pending patent application Ser. No. 08 / 479,935, filed Jun. 7, 1995 in the name of Hillebrand, corresponding to 95/07432; And PCT Application No. U.S., filed March 1, 1995, published September 8, 1995. Co-pending patent application Ser. No. 08 /, filed Feb. 24, 1995 in the name of Kvalnes, Mitchell A. DeLong, Barton J. Bradbury, Curtis B. Motley, and John D. Carter, corresponding to 95/02809 And those disclosed in 390,152.

Antimicrobial and antifungal actives

The composition of the present invention may contain an antimicrobial or antifungal active. The active agents can destroy bacteria, prevent the development of bacteria or prevent the pathogenic action of bacteria. A safe effective amount of antimicrobial or antifungal active agent is preferably added to the composition at about 0.001% to about 10%, more preferably at about 0.01% to about 5%, even more preferably at about 0.05% to about 2%. Can be.

Examples of antimicrobial and antifungal actives include β-lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin, tetracycline, erythromycin, amikacin, 2,4,4'-trichloro-2'-hydroxy diphenyl Ethers, 3,4,4'-trichlorovanilide, phenoxyethanol, phenoxy propanol, phenoxyisopropanol, doxycycline, capreomycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, Hexamidine isethionate, metronidazole, pentamidine, gentamicin, kanamycin, linenemycin, metacycline, metheneamine, minocycline, neomycin, netylmycin, paromomycin, streptomycin, tobramycin, myconazole , Tetracycline hydrochloride, erythromycin, zinc erythromycin, erythromycin estholate, erythromycin stearate, amikacin sulfate, venom Cycline hydrochloride, capreomycin sulfate, chlorhexidine gluconate, chlorhexidine hydrochloride, chlortetracycline hydrochloride, oxytetracycline hydrochloride, clindamycin hydrochloride, ethambutol hydrochloride, metronidazole hydrochloride, pentamidine hydrochloride, Gentamicin sulphate, kanamycin sulphate, linenemycin hydrochloride, metacycline hydrochloride, metheneamine hypofurlate, metheneamine mandelate, minocycline hydrochloride, neomycin sulphate, netylmycin sulphate, paromomycin Sulphate, streptomycin sulphate, tobramycin sulphate, myconazole hydrochloride, ketaconazole, amanpadin hydrochloride, amanpadin sulphate, octopyrrox, parachlorome Xylenol, it did include statins, toll-naphthyl lactate, zinc pyrithione and clotrimazole.

Preferred examples of active agents useful herein are salicylic acid, benzoyl peroxide, 3-hydroxy benzoic acid, glycolic acid, lactic acid, 4-hydroxy benzoic acid, acetyl salicylic 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, benzoylperoxide, tetracycline, ibuprofen, naproxen, hydrocortisone , Acetominophene, resorcinol, phenoxyethanol, phenoxypropanol, phenoxysopropanol, 2,4,4'-trichloro-2'-hydroxy diphenyl ether, 3,4,4'-trichloro Locarvanilide, octopyrox, lidocaine hydrochloride, clotrimazole, myconazole, ketoconazole, nenocycin sulfate, and mixtures thereof.

Sunscreen actives

Exposure to ultraviolet light can cause excessive scaling and texture change of the stratum corneum. Therefore, the composition of the present invention may optionally contain a sunscreen active agent. As used herein, “sunscreen active agent” includes both sunscreen agents and physical sunblocks. Suitable sunscreen actives can be organic or inorganic.

Various conventional organic sunscreen actives are suitable for use herein. See Sagarin et al., Chapter VIII, page 189, Cosmetics Science and Technology (1972) , discloses many suitable active agents. Specific suitable sunscreen actives include, for example: p-aminobenzoic acid, salts thereof and derivatives thereof (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid); Anthranilates (eg o-amino-benzoate; methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters); Salicylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di-propyleneglycol esters); Cinnamic acid derivatives (mentyl and benzyl esters, a-phenyl cinnamonitrile; butyl cinnamoyl pyruvate); Dihydroxycinnamic acid derivatives (umbelliferone, methylumbelliferone, methylaceto-umbelliferone); Trihydroxy cinnamic acid derivatives (esculletin, methylesculletin, daphnetine, and glucosides, esculin and daphnin); Hydrocarbons (diphenylbutadiene, stilbene); Dibenzalacetone and benzalacetophenone; Naphtholsulfonate (sodium salt of 2-naphthol-3,6-disulfonic acid and 2-naphthol-6,8-disulfonic acid); Di-hydroxynaphthoic acid and salts thereof; o- and p-hydroxybiphenyldisulfonate; Coumarin derivatives (7-hydroxy, 7-methyl, 3-phenyl); Diazoles (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl naphthazole, various aryl benzothiazoles); Quinine salts (bissulphates, sulfates, chlorides, oleates, and tannates); Quinoline derivatives (8-hydroxyquinoline salt, 2-phenylquinoline); Hydroxy- or methoxy-substituted benzophenones; Uric acid and viol uric acid; Carbonic acid and its derivatives (eg, hexaethyl ether); (Butyl carbotol) (6-propyl piperonyl) ether; Hydroquinone; Benzophenone (oxybenzene, sulfisobenzone, dioxybenzone, benzoresorcinol, 2,2 ', 4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy-4,4'- Dimethoxybenzophenone, octabenzone; 4-isopropyldibenzoylmethane; butylmethoxydibenzoylmethane; etocrylene; octocrylene; [3- (4'-methylbenzylidene bornan-2-one), terephthal Ildene dicamphor sulfonic acid and 4-isopropyl-di-benzoylmethane.

Among them, 2-ethylhexyl-p-methoxycinnamate (available as PASOL MCX), 4,4'-t-butyl methoxydibenzoyl-methane (commercially available as PASOL 1789), 2-hydroxy-4- Methoxybenzophenone, octyldimethyl-p-aminobenzoic acid, digaloyltrioleate, 2,2-dihydroxy-4-methoxybenzophenone, ethyl-4- (bis (hydroxy-propyl)) aminobenzo 8, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, 2-ethylhexyl-salicylate, glyceryl-p-aminobenzoate, 3,3,5-tri-methylcyclohex Silsalicylate, methylanthranilate, p-dimethyl-aminobenzoic acid or aminobenzoate, 2-ethylhexyl-p-dimethyl-amino-benzoate, 2-phenylbenzimidazole-5-sulfonic acid, 2- (p- Dimethylaminophenyl) -5-sulphonicbenzoxazoic acid, octocrylene and mixtures of these compounds are preferred.

More preferred organic sunscreen active agents useful in the compositions useful in the present invention are 2-ethylhexyl-p-methoxycinnamate, butylmethoxydibenzoyl-methane, 2-hydroxy-4-methoxybenzo-phenone, 2-phenylbenz Imidazole-5-sulfonic acid, octyldimethyl-p-aminobenzoic acid, octocrylene and mixtures thereof.

Also particularly useful in the compositions are sunscreen actives, such as those disclosed in US Pat. No. 4,937,370 to Sabatelli on June 26, 1990 and US Pat. No. 4,999,186 to Sabatelli & Spirnak on March 12, 1991. The sunscreen agent described above has two distinct chromophore moieties that exhibit different ultraviolet radiation absorption spectra in a single molecule. One of the chromophore portions absorbs mainly in the UVB radiation range and the other strongly absorbs in the UVA radiation portion.

Preferred sources of the sunscreen agents of this group include 4-N, N- (2-ethylhexyl) methyl-aminobenzoic acid ester of 2,4-dihydroxybenzophenone; N, N-di- (2-ethylhexyl) -4-aminobenzoic acid ester with 4-hydroxydibenzoylmethane; 4-N, N- (2-ethylhexyl) methyl-aminobenzoic acid ester with 4-hydroxydibenzoylmethane; 4-N, N- (2-ethylhexyl) methyl-aminobenzoic acid ester of 2-hydroxy-4- (2-hydroxyethoxy) benzophenone; 4-N, N- (2-ethylhexyl) -methylaminobenzoic acid ester of 4- (2-hydroxyethoxy) dibenzoylmethane; N, N-di- (2-ethylhexyl) -4-aminobenzoic acid ester of 2-hydroxy-4- (2-hydroxyethoxy) benzophenone; And N, N-di- (2-ethylhexyl) -4-aminobenzoic acid ester of 4- (2-hydroxyethoxy) dibenzoylmethane and mixtures thereof.

Particularly preferred sunscreen actives include 4,4'-t-butylmethoxydibenzoylmethane, 2-ethylhexyl-p-methoxycinnamate, phenyl benzimidazole sulfonic acid, and octocrylene.

A safe effective amount of organic sunscreen active is typically used at about 1% to about 20%, more typically about 2% to about 10% by weight of the composition. The exact amount will depend on the sunscreen or sunscreens selected and the desired Sun Protection Factor (SPF).

Conditioning agent

The composition of the present invention may contain a conditioning agent selected from humectants, moisturizers, or skin conditioners. Various such materials can be used, each of about 0.01% to about 20%, more preferably about 0.1% to about 10%, even more preferably about 0.5% to about 7% by weight of the composition. Can exist at the level of The material includes guanidine; Urea; Glycolic acid and glycolate salts (eg, ammonium and quaternary alkyl ammonium); Salicylic acid; Lactic acid and lactate salts (eg, ammonium and quaternary alkyl ammonium); Aloe vera in any of its various forms (eg, aloe vera gel); Polyhydroxy alcohols such as sorbitol, mannitol, xylitol, erythritol, glycerol, hexanetriol, butanetriol, propylene glycol, butylene glycol, hexylene glycol and the like; Polyethylene glycol; Sugars (eg melibiose) and starch; Sugar and starch derivatives (eg, alkoxylated glucose, fructose, glucosamine); Hyaluronic acid; Lactamide monoethanolamine; Acetamide monoethanolamine; Panthenol; Allantoin; And mixtures thereof, but is not limited thereto. Also useful herein are the propoxylated glycerols described in US Pat. No. 4,976,953 (Orr et al.), Issued December 11, 1990.

Also useful are various C ₁ -C ₃₀ monoesters and polyesters of sugars and related substances. The esters are derived from sugar or polyol moieties and one or more carboxylic acid moieties. Such ester materials are also disclosed in US Pat. No. 2,831,854, US Pat. No. 4,005,196 (Jandacek), issued January 25, 1977; US Patent No. 4,005,195 (Jandacek), issued January 25, 1977, US Patent No. 5,306,516, issued April 26, 1994 (Letton et al.); U.S. Patent No. 5,306,515 (Letton et al.), Issued April 26, 1994; US Patent No. 5,305,514, issued April 26, 1994 to Letton et al .; US Patent 4,797,300 (Jandacek et al.), Issued January 10, 1989; U. S. Patent No. 3,963, 699 (Rizzi et al.), Issued June 15, 1976; US Patent No. 4,518,772 (Volpenhein), issued May 21, 1985; And US Patent No. 4,517,360 (Volpenhein), issued May 21, 1985.

Thickeners (including thickeners and gelling agents)

The compositions of the present invention comprise one or more midpoints, preferably from about 0.1% to about 5%, more preferably from about 0.1% to about 34%, even more preferably from about 0.25% to About 3% by weight.

Non-limiting examples of thickeners include those selected from:

a) carboxylic acid polymer

The polymers are crosslinking compounds containing acrylic acid, substituted acrylic acid, and at least one monomer derived from salts and esters of the acrylic acid and substituted acrylic acid, wherein the crosslinker contains at least two carbon-carbon double bonds, It is derived from a polyhydric alcohol. Polymers useful in the present invention include U. S. Patent No. 5,087, 445 (Haffey et al.), Issued February 11, 1992; U.S. Patent No. 4,509,949 (Huang et al.), Issued April 5, 1985; US Patent No. 2,798,053 (Brown), issued July 2, 1957; And CTFA International Cosmetic Ingredient Dictionary , 4th edition, 1991, pp. 12 and 80, further described.

Examples of commercially available carboxylic acid polymers useful herein include carbomers, which are homopolymers of acrylic acid crosslinked with allyl ethers of pentaerythritol or sucrose. Carbomer from Carbopol from BF Goodrich 900 series (for example, Carbopol 954). Other suitable carboxylic acid polymeric formulations also include copolymers of C _10-30 alkyl acrylates with one of acrylic acid, one or more monomers of methacrylic acid, or short chain (eg, C _1-4 alcohol) esters thereof. Wherein the crosslinker is allyl ether of pentaerythritol or sucrose. The copolymers are known as acrylate / C _10-30 alkyl acrylate crosslinkers and are available from Carbopol from BF Goodrich. 1342, Carbopol 1382, Pemulen TR-1, and Pemulen TR-2. In other words, examples of carboxylic acid polymer thickeners useful herein are those selected from carbomers, acrylates / C _10-30 alkyl acrylate crosspolymers, and mixtures thereof.

b) crosslinked polyacrylate polymers

The compositions of the present invention may optionally contain both cationic and nonionic polymers, crosslinked polyacrylate polymers which are useful as thickeners or gelling agents, typically comprising cationic polymers. Examples of useful crosslinked nonionic polyacrylate polymers and crosslinked cationic polyacrylate polymers are described in US Pat. No. 5,100,660, issued March 31, 1992 to Hawe et al .; US Patent 4,849,484 (Heard), issued July 18, 1989; U.S. Patent No. 4,835,206 (Farrar et al.), Issued May 30, 1989; US Patent No. 4,628,078 issued December 9, 1986 to Glover et al .; U.S. Patent No. 4,599,379 to Flesher et al., Issued July 8, 1986; And EP 228,868 (Farrar et al.) Published July 15, 1987.

c) polyacrylamide polymers

The compositions of the present invention may optionally contain polyacrylamide polymers, in particular nonionic polyacrylamide polymers including substituted branched or unbranched polymers. More preferred among the above polyacrylamide polymers are the nonionic polymers of the CTFA name polyacrylamide and isoparaffin and laureth-7, available under the trade name Sepigel 305 from Seppic Corporation (Fairfield, NJ).

Other polyacrylamide polymers useful herein include multi-block copolymers of acrylamide and substituted acrylamide with acrylic acid and substituted acrylic acid. Commercial examples of such multi-block copolymers include Lipo Chemicals, Inc. Hypan SR150H, SS500V, SS500W, SSSA100H from (Patterson, NJ) are included.

d) polysaccharides

Various polysaccharides are useful herein. "Polysaccharide" refers to a gelling agent that contains a repeating sugar (eg, carbohydrate) unit backbone. Non-limiting examples of polysaccharide gelling agents include cellulose, carboxymethylhydroxyethylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, methyl hydroxy And those selected from oxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Also useful herein are alkyl substituted celluloses. In this polymer, the hydroxy group of the cellulose polymer is hydroxyalkylated (preferably hydroxyethylated or hydroxypropylated) to form hydroxyalkylated cellulose, which is then C _10-30 straight or branched chain via an ether bond. It is further modified with an alkyl group. Typically, the polymers are ethers of C _10-30 straight or branched chain alcohols with hydroxyalkylcelluloses. Examples of alkyl groups useful herein include stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, cocoyl (ie, alkyl groups derived from alcohols of coconut oil), palmityl, oleyl, linoleyl, linol And those selected from renyl, ricinoleyl, behenyl, and mixtures thereof. Preferred among the alkyl hydroxyalkyl cellulose ethers is a material whose CTFA name is cetyl hydroxyethylcellulose, which is an ether of hydroxyethylcellulose and cetyl alcohol. The material is tradename Natrosol from Aqualon Corporation (Wilmington, Germany). Sold as CS Plus.

Other useful polysaccharides include scleroglucans, a straight chain of (1-3) linked glucose units with (1-6) linked glucose every 3 units, commercially available from Michel Mercier Products Inc. (Mountainside, NJ) from Clearogel ^™ CS11.

e) sword

Other thickening and gelling agents useful herein include materials primarily derived from natural sources. Non-limiting examples of the gelling gums include acacia, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxypropyltrimonium Chloride, hectorite, hyalurophosphate, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclero Lithium gum, sodium carboxymethyl dextran, sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.

Preferred compositions of the invention are selected from the group consisting of carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, and mixtures thereof, more preferably carboxylic acid polymers, polyacrylamide polymers, and mixtures thereof. Thickeners are included.

Although various optional ingredients may be included in the compositions of the claimed methods, the compositions are preferably free of water dispersible lecithin and panthenol. As used herein, “without” means that a compound or component may not be detected in the composition.

Composition preparation

Compositions useful in the methods of the invention are usually prepared by conventional methods known in the art of preparing topical compositions. This method usually involves mixing the components in a relatively uniform state with or without heating, cooling, application of vacuum, etc. in one or more steps.

How to regulate keratin tissue status

The compositions of the present invention are useful for modulating keratin tissue conditions in mammals. Such regulation of keratin tissue conditions may include prophylactic and therapeutic regulation. More specifically, these modulating methods may include thickening of keratinous tissue (ie, the construction of the epidermal and / or dermal layer of the skin and, where applicable, the keratin layer of the skin and hair axis), the prevention and / or delay of atrophy of mammalian skin, mammal Prevention and / or delay of the appearance of spider blood vessels and / or red spots of the skin, prevention and / or delay of the appearance of dark circles under the mammal's eyes, prevention and / or delay of poor color of the mammalian skin, prevention of sagging of the mammalian skin And / or delay, softening and / or smoothing of the lips, hair and nails of a mammal, and prevention and / or alleviation of itching of mammalian skin.

Modulation of the keratinous tissue condition comprises the application of a safe effective amount of the composition of the invention to keratinous tissue. The amount of applied composition, frequency of application and duration of use will vary greatly depending on the level of control desired in terms of the level of xanthine compound and / or other components and the level of keratin tissue damage present or expected to occur, for example.

In a preferred embodiment, the composition is chronically applied to the skin. "Chronic topical application" means even more preferably over a prolonged period of life of a subject, preferably for a period of at least about 1 week, more preferably for a period of at least about 1 month, even more preferably for a period of at least about 3 months, even more preferably For a period of at least about 6 months, even more preferably for a period of at least about 1 year. While the benefits are obtainable after various maximum periods of use (eg 5, 10 or 20 years), it is desirable that topical application persist through the life of the subject. Typically, the application will be about once a day for a long time, but the application rate can vary from about once a week to about three times a day.

Various amounts of the compositions of the present invention can be used to provide the benefit of skin appearance and / or touch. Typically, the amount of the composition applied per application is in composition mg / skin cm ² , from about 0.1 mg / cm ² to about 10 mg / cm ² . Particularly useful dosages are from about 1 mg / cm ² to about 2 mg / cm ² .

Modulation of keratinous tissue conditions is preferably a skin lotion, cream, gel, foam, ointment, paste, emulsion, spray designed to remain in the skin or other keratin structures for some aesthetic, prophylactic, therapeutic or other benefit. It is preferably carried out by applying a composition in the form of a conditioner, tonic, cosmetic, lipstick, foundation, nail polish, aftershave and the like (ie a "leave-on" composition). After applying the composition to the skin, at least about 15 minutes, more preferably at least about 30 minutes, even more preferably at least about 30 minutes, even more preferably at least about 1 hour, even more preferably at least several hours, such as about 12 It is desirable to remain on the skin for a period of time or less. Any part of the exterior of the face, hair and / or nail, such as the face, lips, sub-eye area, eyelids, scalp, neck, torso, arms, hands, legs, feet, nails, toenails, scalp hair, eyelashes, eyebrows, etc. Can also be processed.

Another approach to ensure continuous exposure of the skin to at least a minimum level of xanthine compound is to apply the compound, for example by use of a patch applied to the face. This approach is particularly useful for problem skin areas that require more intensive treatment (eg, facial crows feet areas, crow's feet, areas under the eyes, etc.). The patch can be closed, semi-closed or non-closed, and can be adhesive or non-adhesive. The xanthine compound containing composition may be contained in the patch or applied to the skin prior to application of the patch. The patch may contain additional active agents such as chemical initiators for exothermic reactions as described in PCT application WO 9701313 [Burkett et al.]. The patch is preferably for a period of at least about 5 minutes, more preferably at least about 15 minutes, even more preferably at least about 30 minutes, even more preferably at least about 1 hour, most preferably at night as a form of night therapy Remains on the skin

The compositions of the present invention can be used to prevent or / or delay the appearance of spider vessels and / or red stains on mammalian skin, dark circles under the mammalian eyes, and to users or potential users of the compositions (hereinafter referred to as users). And / or prophylaxis and / or delay of the appearance of swollen eyes, exfoliation of mammalian skin, prevention and / or delay of bad color of mammalian skin, prevention and / or delay of sagging of mammalian skin, softening of mammalian lips, hair and nails And / or information indicating the use of the composition to provide one or more benefits, including smoothing, and the prevention and / or alleviation of pruritus of the mammalian skin. This information may also include instructions for the user who may benefit from the above, including, for example, the method steps described above. The expression "with information" is not limited to printing information directly on the container of the composition itself (including indirectly by printing directly on the container itself or indirectly by a label attached to the container), or a brochure, By providing in other ways, including print advertisements, electronic advertisements, and / or other advertisements, to inform the user of the composition. Thus, such information may include text, photos, and the like.

The following examples further illustrate and demonstrate embodiments within the scope of the invention. The examples are provided for illustrative purposes only and should not be construed as limiting the invention as many variations thereof are possible without departing from the spirit and scope of the invention.

Example 1

Skin creams are prepared by conventional methods from the following ingredients.

Ingredients (CTFA Name) weight% Phase A: Water U.S.P 2.00 Butylene Glycol 0.25 Glidant Plus 0.10 Phase B: Water U.S.P 70.55 Disodium EDTA 0.10 Panthenol 0.50 glycerin 10.00 Theophylline 5.00 Phase C: DC200 / 10cst 2.00 Alamol E 3.00 Cetyl palmitate 0.50 Cetyl alcohol 0.75 Stearyl alcohol 0.75 Brij721 0.80 Brij72 1.20 Phase D: Sepigel 305 2.50

Phase A components are blended using a suitable mixer (eg, Tekmar model RW20DZM), and heated with mixing to melt the components. Separately, phase B components except theophylline are blended using a suitable mixer and heated to a temperature of 70-75 ° C. with stirring. Theophylline is added at this temperature. Separately, phase C components are blended and heated to a temperature of 70-75 ° C. with stirring. At this temperature, phase C is added to phase B and ground for 5 minutes (eg using a Tekmar T50 Mill). Phase D is then added and mixed for 5 minutes. After cooling to 50 ° C., phase A is added.

The composition is applied to the facial skin of a subject in need of treatment at a rate of ² mg (composition) / cm ² (skin) once or twice a day for at least 3-6 months.

Example 2

Skin creams are prepared from the following ingredients by conventional methods.

Ingredients (CTFA Name) weight% Phase A: Water U.S.P 66.80 glycerin 7.00 Glidant Plus 0.10 Theophylline 5.00 Disodium EDTA 0.10 Phase B: Alamol E 5.00 Mineral oil 5.00 Sepa Cotonate 2.00 Permethyl 101A 3.00 Alasel P135 4.00 Petroleum 2.00

Form phase A (water phase) in a suitable container filled with water as follows:

The remaining ingredients are added slowly while stirring and heated to 55 ° C.

The components of phase B are added and stirred together to form phase B (oil phase) in a separate suitable container. Heated to 50 ° C. and stirred.

Slowly add phase A to phase B with stirring to grind for 15 minutes.

The composition is applied to the facial skin of a subject in need of treatment at a rate of ² mg (composition) / cm ² (skin) once or twice a day for at least 3-6 months.

Example 3

Skin creams are prepared from the following ingredients by conventional methods.

Ingredient (CTFA Name) weight% Phase A: Water U.S.P 2.00 Butylene Glycol 0.25 Glidant Plus 0.10 Phase B: Water U.S.P 70.55 Disodium EDTA 0.10 Pantenol 0.50 glycerin 10.00 Theobromine 5.00 Phase C: DC200 / 10cst 2.00 Alamol E 3.00 Cetyl palmitate 0.50 Cetyl alcohol 0.75 Stearyl alcohol 0.75 Brij721 0.80 Brij 72 1.20 Phase D: Sepigel 305 2.50

Phase A components are blended using a suitable mixer (eg, Tekmar model RW20DZM) and then heated with mixing to melt the components. Separately, phase B components except theobromine are blended using a suitable mixer and heated to a temperature of 70-75 ° C. with stirring. Theobromine is added at this temperature. Separately, the phase C components are blended and heated to a temperature of 70-75 ° C. with stirring. At this temperature, phase C is added to phase B and ground for 5 minutes (eg using a Tekmar T50 Mill). Phase D is then added and mixed for 5 minutes. After cooling to 50 ° C., phase A is added.

The composition is applied to the facial skin of a subject in need of treatment at a rate of ² mg (composition) / cm ² (skin) once or twice daily for at least 3-6 months.

While specific embodiments of the invention have been described, it will be apparent to those skilled in the art that various modifications and variations can be made to the invention without departing from the spirit and scope of the invention. It is intended that the appended claims cover all such modifications as fall within the scope of the invention.

Claims (10)

A method of controlling visual and / or tactile discontinuity in mammalian skin tissue, the method comprising topically applying a safe and effective amount of a retinoid composition to a mammal's skin in need of said treatment. How to: a) a safe effective amount of an organizing agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; And b) Dermatologically acceptable carriers for tissue agents. A method of preventing and / or delaying the appearance of spider vessels and / or red stains on mammalian skin, the method comprising topically applying a safe effective amount of a composition to a mammal's skin in need of said treatment comprising: How to: a) a safe effective amount of spider vascular and / or red stain repair agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; And b) Dermatologically acceptable carrier for the repair agent. A method of preventing and / or delaying the appearance of dark circles and swollen eyes on the skin under a mammal's eye, the method comprising topically applying a safe effective amount of a composition comprising the following to the skin around the eye of a mammal in need of such treatment: Method characterized by: a) a safe and effective amount of dark circle / swollen eye repair agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; And b) Dermatologically acceptable carrier for the repair agent. A method of preventing and / or delaying the slowness of mammalian skin, the method comprising topically applying a safe effective amount of a composition to a mammalian skin in need of said treatment, said composition comprising: a) a safe effective amount of poor color recovery agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; And b) Dermatologically acceptable carrier for the repair agent. A method of preventing and / or delaying sagging of mammalian skin, the method comprising topically applying a safe effective amount of a composition to a mammalian skin in need of said treatment comprising: a) a safe effective amount of a sagging repair agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; And b) Dermatologically acceptable carrier for the repair agent. A method of exfoliating mammalian skin, comprising topically applying to a mammalian skin in need of a skin exfoliation treatment a safe effective amount of a composition comprising: a) a safe effective amount of a release agent essentially consisting of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; And b) Dermatologically acceptable carriers for the delaminator (the composition is free of L-carnitine and derivatives, lysosperphingolipids and salts and sphingosine derivatives thereof). A method of softening and / or smoothing a mammal's lips, hair and nails, the method comprising topically applying a safe effective amount of a composition comprising the following to the mammal's lips, hair and nails in need of such treatment: Way: a) a safe effective amount of softening / smoothing agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; And b) Dermatologically acceptable carrier for softening / smoothing agents. A method of preventing and / or alleviating pruritus of mammalian skin, the method comprising topically applying a safe and effective amount of a procaine-free composition to the mammalian skin in need of said treatment, comprising: a) a safe effective amount of an antipruritic agent consisting essentially of a xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; And b) Dermatologically acceptable carrier for antipruritic agents. The composition of claim 1 wherein the composition is a release agent, anti-acne active agent, vitamin B ₃ compound, retinoid, antioxidant, radical scavenger, chelator, anti-inflammatory agent, local anesthetic, tanning active, skin lightening agent, anti-cellulite agent And a safe effective amount of a skin care active agent selected from flavonoids, antimicrobial actives, antifungal actives, sunscreen actives, conditioning agents, structuring agents, thickeners, and combinations thereof. a) a safe effective amount of xanthine compound selected from the group consisting of theophylline, theobromine and combinations thereof; b) a safe effective amount of niacinamide; And c) A composition suitable for regulating skin condition comprising a xanthine compound and a dermatologically acceptable carrier for niacinamide.