Stabilization of resorcinol compounds in cosmetic compositions

Abstract

A topical cosmetic composition comprising a 4-substituted resorcinol derivative together with N-acetylmethionine exhibits improved storage stability and oxidative stability. A method for stabilizing 4-ethylresorcinol or 4-hexylresorcinol in a composition comprising a cosmetically acceptable vehicle by adding acetylmethionine to the composition in an amount sufficient to stabilize the 4-ethylresorcinol or 4-hexylresorcinol. Use of N-acetylmethionine and a stabilized 4-substituted resorcinol derivative in the preparation of a topical cosmetic composition.

Description

[Technical field]

[0001] Provided herein are topical cosmetic compositions comprising 4-substituted resorcinol derivatives stabilized with acetylmethionine. [Background technology]

[0002] Beauty in the eyes of the viewer is influenced by many physiological and genetic factors. The basis of natural appearance as beauty is the skin, including the hair. Ideal skin should be smooth and even, free of obvious surface blemishes, in addition to having a clear appearance with an even color distribution. Skin and hair problems in the elderly can result from a variety of extrinsic or intrinsic factors, such as harmful ultraviolet rays from the sun, environmental exposure, stress, fatigue, disease, or a combination thereof.

[0003] Resorcinol (1,3-benzenediol) derivatives have been used to provide cosmetic benefits to skin and hair. 4-Substituted resorcinol derivatives and their preparations have been used for skin whitening and other cosmetic applications. See, for example, U.S. Pat. No. 4,959,393, U.S. Pat. No. 6,132,740, U.S. Patent Application Publication No. 2008 / 0131382, and Japanese Published Patent Applications Nos. JP 2001-01 0925 and JP 2000-327557. Resorcinol-type skin whitening agents that can be synthesized starting from coumarin are disclosed in U.S. Patent Application Publication No. 2004 / 0042983. However, some of these compounds can be difficult to formulate due to instability in cosmetically acceptable vehicles. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Patent No. 4,959,393 [Patent Document 2] U.S. Patent No. 6,132,740 [Patent Document 3] US Patent Application Publication No. 2008 / 0131382 [Patent Document 4] JP 2001-010925 A [Patent Document 5] JP 2000-327557 A [Patent Document 1] US Patent Application Publication No. 2004 / 0042983 Summary of the Invention [Problem to be solved by the invention]

[0005] Oxidative instability is an undesirable property of 4-substituted resorcinols. Thus, there is a need for agents that stabilize 4-substituted resorcinols against oxidation. In particular, there is a need for agents that prevent the oxidation of 4-substituted resorcinols.

[0006] It would be desirable to have a topical cosmetic composition containing a resorcinol derivative that is stabilized against factors such as discoloration, oxidation, general storage stability, etc. The compositions containing 4-alkylresorcinols stabilized with N-acetylmethionine (AceMet) described herein fulfill this need. [Means for solving the problem]

[0007] a. about 0.00001 to about 10% N-acetylmethionine; b. from about 0.00001 to about 10% of a 4-substituted resorcinol derivative; and c. A vehicle or carrier.

[0008] The 4-substituted resorcinol derivatives are stabilized against degradation / discoloration / oxidation by including N-acetylmethionine in the composition, which comprises a cosmetically effective amount of a resorcinol compound and N-acetylmethionine in an amount sufficient to stabilize the resorcinol compound against chemical degradation as evidenced by discoloration.

[0009] The resorcinol derivatives provided herein, as defined below, are useful for the treatment or prevention of one or more cosmetic conditions desired by a subject in need of treatment, such as preventing, alleviating, reducing or treating the signs or appearance of undesirable pigmentation of skin affected by one or more conditions.

[0010] The 4-substituted resorcinol derivatives have the general formula I: [ka]

[0011] In the formula, each R1 and R2 is independently a hydrogen atom, -CO-R, -COO-R, or CONHR, where R is C1-C 18 represents a hydrocarbon; R3 is C1-C 18 represents a hydrocarbon or has the general formula (II): [ka] In the formula, X is hydrogen; OR 1 [R 1 represents hydrogen, (C1-C6) alkyl or aryl-(C1-C6) alkyl. 2 [R 2 represents (C1-C6)alkyl, aryl-(C1-C6)alkyl or phenyl; (C1-C6)alkyl; aryl-(C1-C6)alkyl; or NHR 1 [R 1 is defined as above.] stands for; n is 0 to 3; The dashed lines indicate optional double bonds;

[0012] Preferred are 4-straight chain alkylresorcinols, 4-branched alkylresorcinols, 4-cycloalkylresorcinols, and mixtures thereof.

[0013] More particularly preferred resorcinol derivatives include 4-ethylresorcinol, 4-isopropylresorcinol, 4-hexylresorcinol and 4-cyclohexylresorcinol, as well as their O-acylated versions.

[0014] In another embodiment, a 4-substituted resorcinol derivative stabilized by N-acetylmethionine; b. optional skin benefit agents; and c. A cosmetically acceptable vehicle A stabilized cosmetic composition comprising: N-acetylmethionine present in an amount of about 0.0001% to about 5% by weight of the cosmetic composition; The weight ratio of the N-acetylmethionine to the 4-substituted resorcinol derivative is about 10,000:1 to about 1:100,000. A cosmetic composition is provided.

[0015] The compositions of the present invention are aesthetically pleasing and the resorcinol derivatives contained therein have improved storage / color / oxidative stability.

[0016] Also provided is a method of stabilizing (against oxidation, discoloration, storage, etc.) 4-hexylresorcinol in a composition comprising a cosmetically acceptable vehicle by adding N-acetylmethionine to the composition in an amount sufficient to stabilize said 4-hexylresorcinol.

[0017] Also provided is the use of N-acetylmethionine and any 4-substituted resorcinol derivative in the manufacture of a cosmetic composition for topical application to the skin of an individual in need of treatment.

[0018] In another variation, provided herein is a method of controlling a skin condition by topically applying to the skin of an individual in need of treatment an effective amount of a composition of the present invention comprising a 4-substituted resorcinol derivative and N-acetylmethionine.

[0019] Also provided herein are articles of manufacture that include instructions instructing a user to apply a composition, such as a skin care composition, that includes one or more 4-substituted resorcinol derivatives, that also includes N-acetyl methionine as a stabilizer. The composition can include pharma- ceutically and / or dermatologically acceptable carriers and vehicles.

[0020] The compositions of the present invention are aesthetically pleasing and have improved storage / oxidative stability. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] definition As used herein, an "individual" is a mammal, particularly a human. It is understood that use "in" an individual can also include use "on" an individual. That is, use "on" an individual can include internal use, external use, or both, depending on the context of use.

[0022] As used herein, "administration to skin in need of such treatment" means contacting (e.g., by hand or with an applicator such as, but not limited to, a tissue, tube, roller, spray, or patch) the area of ​​skin in need of such treatment or an area of ​​skin adjacent to the area of ​​skin in need of such treatment.

[0023] As used herein, "composition" means a composition suitable for topical administration to the skin.

[0024] As used herein, the term "cosmetic composition" is intended to describe compositions for topical application to human skin, such as leave-on and wash-off products.

[0025] The term "skin" as used herein includes the skin of the human face, neck, chest, back, arms, armpits, hands, feet, and scalp.

[0026] Except in the examples, or where otherwise expressly indicated, all numbers in this description expressing quantities of ingredients or reaction conditions, physical properties of ingredients, and / or uses should be understood as being modified by the word "about." Unless otherwise indicated, all amounts are by weight of the composition.

[0027] For the avoidance of doubt, the word "comprising" is intended to mean "including" but not necessarily "consisting of" or "composed of." In other words, the listed steps or options need not be exhaustive.

[0028] For all compositions described herein and for all methods of using the compositions described herein, the composition may comprise or "consist essentially of" the listed ingredients or steps. When a composition is described as "consisting essentially of" listed ingredients, the composition may comprise the listed ingredients and may include other ingredients that have a negligible effect on the skin or the skin condition being treated, but does not include any other ingredients that have a substantial effect on the skin or the skin condition being treated other than the ingredients explicitly listed, or when the composition includes additional ingredients other than those listed that have a substantial effect on the skin or the skin condition being treated, the composition does not include the additional ingredients in a concentration or amount sufficient to substantially affect the skin or the skin condition being treated. When a method is described as "consisting essentially of" listed steps, the method may include the listed steps and may include other steps that do not substantially affect the skin or the skin condition being treated, but the method does not include any other steps other than the steps explicitly listed that have a substantial effect on the skin or the skin condition being treated.

[0029] As used herein, the terms "cosmetically acceptable" or "dermatologically acceptable" mean that the composition or ingredient so described is suitable for use in contact with the skin, particularly human skin, without undue toxicity, incompatibility, instability, irritation, or allergic response.

[0030] As used herein, the term "cosmetically acceptable carrier", "cosmetically acceptable excipient", "dermatologically acceptable carrier" or "dermatologically acceptable excipient" includes any cosmetically acceptable or dermatologically acceptable solvent, dispersion medium, coating, antibacterial and antifungal agents, isotonicity agents and absorption delaying agents. Except insofar as a conventional medium or agent is incompatible with the active ingredient, its use in the cosmetic composition is contemplated. Supplementary active ingredients can also be incorporated into the composition. A cosmetically acceptable carrier is suitable for topical application to the skin, has good aesthetic properties, is compatible with the active agent and any other ingredients described herein, and poses minimal or no safety or toxicity concerns. The amount of safe and effective carrier is about 50% to about 99.99% or about 50% to about 99%, preferably about 80% to about 99.9% or about 75% to about 99%, more preferably about 90% to about 98%, and most preferably about 90% to about 95% or about 85% to about 95% of the composition. Percentages are preferably by weight.

[0031] As used herein, the terms "skin condition," "dermatologic condition," and "dermatological condition" are used interchangeably.

[0032] As used herein, the term "sunscreen" may include, but is not limited to, organic or inorganic sunscreens, such as methoxycinnamate, oxybenzone, avobenzone, etc.; sunblocks, such as titanium dioxide and zinc oxide; and skin protectants; or mixtures thereof.

[0033] As used herein, the term "topical application" means applying or spreading the compositions described herein onto the surface of the skin.

[0034] As used herein, "alkyl" is intended to include saturated, straight or branched hydrocarbon chains having the specified number of carbon atoms. In one embodiment, an alkyl group can have from 1 to 12 carbon atoms. "Alkylene" is intended to include divalent saturated, straight or branched hydrocarbon chains having the specified number of carbon atoms. In one embodiment, an alkylene group can have from 1 to 12 carbon atoms.

[0035] As used herein, "cycloalkyl" is intended to encompass a saturated cyclic hydrocarbon chain having the specified number of carbon atoms. In one embodiment, a cycloalkyl group can have from 3 to 12 carbon atoms.

[0036] As used herein, "alkenyl" is intended to encompass a straight or branched hydrocarbon chain having at least one carbon-carbon double bond. In one embodiment, an alkenyl group can have from 2 to 12 carbon atoms.

[0037] As used herein, "aryl" is intended to include aromatic hydrocarbons such as, for example, substituted or unsubstituted phenyl or naphthyl groups.

[0038] Although the compounds described herein may occur and be used as neutral (non-salt) compounds, the description is intended to encompass all salts of the compounds described herein, as well as methods of using such salts of the compounds. In one embodiment, the salts of the compounds include pharma- ceutically acceptable salts and / or dermatologically acceptable salts. Cosmetically acceptable salts are salts that can be applied to human and / or animal skin and that, upon application, retain at least a portion of the bioactivity of the free compound (neutral or non-salt compound). The desired salt of a basic compound can be prepared by methods known to those skilled in the art by treating the compound with an acid. Examples of inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids include, but are not limited to, formic acid, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, sulfonic acids, and salicylic acid. Salts of basic compounds with amino acids, such as aspartate and glutamate, can also be prepared. Examples of inorganic salts of acidic compounds include, but are not limited to, alkali metal and alkaline earth salts, such as sodium, potassium, magnesium, and calcium salts; ammonium salts; and aluminum salts. Examples of organic salts of acidic compounds include, but are not limited to, procaine, dibenzylamine, N-ethylpiperidine, N,N-dibenzylethylenediamine, triethylamine, or trialkylamine salts. Salts of acidic compounds with amino acids, such as lysine salts, can also be prepared.

[0039] composition 4-Substituted resorcinol derivatives Resorcinol derivatives are known compounds and can be easily obtained, for example, by a method of condensing a saturated carboxylic acid and resorcinol in the presence of zinc chloride and reducing the resulting condensate with zinc amalgam / hydrochloric acid (Lille. J. Bitter, LA. Peiner. V, Tr. Nauch-Issled. Inst. slantsev 1969, No. 18, 127), or by a method of reacting resorcinol with a corresponding alkyl alcohol in the presence of an alumina catalyst at a high temperature of 200 to 400°C (British Patent No. 1,581,428).

[0040] The compositions of the present invention comprise an effective amount of a resorcinol derivative of formula (I): [ka]

[0041] During the ceremony, Each R1 and R2 independently represents a hydrogen atom, -CO-R (an acyl group), -COO-R, or CONHR; the latter three are each represented by formula A below: [ka] where R is a saturated or unsaturated, linear, branched or cyclic C1-C 18 In a preferred embodiment, each or both of R1 and / or R2 represents hydrogen. In a more preferred embodiment, both R1 and R2 represent hydrogen.

[0042] R3 is (1) Saturated or unsaturated, linear, branched or cyclic C1-C 18 Hydrocarbons, preferably C2-C 12 Hydrocarbons; or (2) a group of the following general formula (II): [ka] represents During the ceremony, X represents hydrogen; OR1 [R1 represents hydrogen, (C1-C6) alkyl or aryl-(C1-C6) alkyl. ]; OCOR2 [R2 represents (C1-C6) alkyl, aryl-(C1-C6) alkyl or phenyl. ]; (C1-C6) alkyl; aryl-(C1-C6) alkyl; or NHR1 [R1 is as defined above. ]; n is 0 to 3; the dashed lines represent optional double bonds.

[0043] For example, when n is 0, the group of formula II is a 5-membered ring; when n is 1, the group is a 6-membered ring; when n is 2, it is a 7-membered ring; and when n is 3, it is an 8-membered ring.

[0044] 4-Substituted resorcinols: linear or branched In the above formula (1), the group represented by R3, preferably having 2 to 12 carbon atoms and linear in arrangement, may include ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl. These linear alkyl groups may be substituted at one or more hydrogen atoms with methyl or ethyl groups. Specific examples of substituted alkyl groups include isopropyl, isobutyl, isoamyl, 2-methylhexyl, etc. Preferred alkyl groups are those where R3 is ethyl, propyl, isopropyl, butyl, pentyl, hexyl, heptyl or octyl. Most preferred alkylresorcinols are those where R3 is ethyl, isopropyl or hexyl.

[0045] 4-Cycloalkylresorcinols When R3 is a resorcinol derivative of formula (I) representing the structure of general formula (II) above, the resorcinol derivative is referred to herein as a 4-cycloalkylresorcinol and is represented by the following general formula (III): [ka]

[0046] In general formula (III) (and formula (II) above), X represents hydrogen; OR1 [R1 represents hydrogen, (C1-C6) alkyl or aryl-(C1-C6) alkyl. ]; OCOR2 [R2 represents (C1-C6) alkyl, aryl-(C1-C6) alkyl or phenyl. ]; (C1-C6) alkyl; aryl-(C1-C6) alkyl; or NHR1 [R1 is as defined above. ]; n is 0 to 3; the dashed line indicates an optional double bond at that position.

[0047] Examples of more specific embodiments of 4-cycloalkylresorcinols include the following: (a) A compound of formula (III) in which a single bond connects two carbon atoms with a dashed line; (b) a compound of formula (III) wherein n is 1; (c) a compound of formula (III) wherein X is hydrogen; (d) compounds of formula (III) where X is hydrogen, methyl or ethyl; (e) a compound of formula (III) wherein n is zero; (f) compounds of formula (III) wherein n is 2; and (g) Compounds of formula (III) wherein X is benzyloxy etc.

[0048] Preferred compounds of formula (III) are 4-cyclohexylresorcinol, 4-cycloheptylresorcinol, and 4-cyclooctylresorcinol. The most preferred compound of formula (III) is 4-cyclohexylresorcinol.

[0049] The amount of the resorcinol derivative is in the range of about 0.00001 to about 10% by weight, preferably about 0.001 to about 7% by weight, and most preferably about 0.01 to about 5% by weight, of the total amount of the cosmetic composition.

[0050] N-Acetylamino acids The present inventors have found that N-acetylamino acids inhibit the oxidation of 4-substituted resorcinol derivatives. Preferably, according to the present invention, N-acetylamino acids are used to stabilize 4-substituted resorcinols incorporated into cosmetic compositions.

[0051] N-acetylmethionine ("AceMet") is preferred and, in the context of the present invention, has the following chemical structure: [ka]

[0052] Acetyl methionine (CAS number 1115-47-5 for Acetyl-DL-methionine) and N-acetyl-L-methionine (CAS number 65-82-7 for "AceMet") have been included in cosmetic applications. For the present invention, N-acetyl-L-methionine ("AceMet") is preferred due to its enhanced solubility profile (water solubility, logP and logD) over L-methionine.

[0053] AceMet is a nutritionally and metabolically equivalent form of the essential amino acid L-methionine (L-Met), the latter being used as an intermediate in the biosynthesis of S-adenosylmethionine (SAMe) - an essential nutrient for maintaining optimal cellular energy balance - as well as many important biomolecules, including cysteine, carnitine, taurine, lecithin, and phosphatidylcholine. AceMet has also been shown to have detoxifying properties (e.g., antidote for paracetamol overdose, detoxification of benzene derivatives) and is presumed to be stable in formulations (WO0040217, WO05055947). N-acetylamino acids (e.g., AceMet) have been used as part of a combination of multiple active agents for topical cosmetic applications to treat skin disorders (related to aging, hair, nails, etc.) (WO00 / 40717 to Tristrata Inc).

[0054] N-acetylmethionine is available from several suppliers, including Sigma-Aldrich.

[0055] The compositions of the invention generally contain from about 0.00001 to about 50% AceMet and from about 0.00001 to about 50% 4-substituted resorcinol. A particular advantage of the compositions of the invention is that the 4-substituted resorcinol can be stabilized against oxidation by AceMet.

[0056] The amount of AceMet effective to inhibit oxidation of the 4-substituted resorcinol derivative can be determined by experimentation. AceMet and the 4-substituted resorcinol derivative are present in the composition in a weight ratio of AceMet:resorcinol of 1:10000 to 10000:1, preferably 1:1000 to 1:5000, more preferably 1:1 to 1:1000.

[0057] Preferably, the amount of AceMet in the cosmetic composition ranges from about 0.00001% to about 10%, more preferably from about 0.0001% to about 5% by weight, and most preferably from about 0.0001% to about 2%.

[0058] Optional ingredients Any of the compounds described herein can be mixed with other ingredients.Examples of such ingredients include oily ingredients such as hydrocarbons, fats and oils such as liquid paraffin, squalene, petrolatum such as Vaseline® (registered trademark of Conopco Corp., Englewood Cliffs, New Jersey), cetyl alcohol, isostearyl alcohol, cetyl-2-ethylhexanoate, 2-octyldodecyl alcohol, glycerin, glycerin triisostearate, nut oils, and lanolin, as well as waxes, silicones, surfactants, thickeners, neutralizers, disinfectants, germicides, antioxidants, powder ingredients, pigments, perfumes, ultraviolet light absorbers, medicines, sequestering agents, and pH adjusters.

[0059] Skin Benefit Agents The cosmetic compositions of the present invention can be used in personal care and personal wash products, such as, for example, lotions, soaps, deodorants, etc. The N-acetylmethionine compounds and stabilizers that form the compositions of the present invention may have other useful functions when incorporated into personal care compositions.

[0060] Preferred personal care compositions are suitable for application to human skin and optionally, but preferably, contain a skin benefit agent. Suitable skin benefit agents include anti-aging agents, wrinkle reducing agents, skin lightening agents, anti-acne agents, and sebum reducing agents. Examples of these include alpha-hydroxy acids and esters, beta-hydroxy acids and esters, polyhydroxy acids and esters, kojic acid and esters, ferulic acid and ferulate derivatives, vanillic acid and esters, diacids (such as sebacid and azoleic acid) and esters, retinol, retinal, retinyl esters, hydroquinone, t-butylhydroquinone, mulberry extract, licorice extract, 1-methylnicotinamide chloride, and resorcinol derivatives other than the above 4-substituted resorcinol derivatives.

[0061] The active compounds described herein may also be used in combination with skin peels (such as glycolic acid or trichloroacetic acid face peels) or skin exfoliants (such as retinoic acid or retinoids such as retinol) to lighten skin tone and prevent repigmentation. The appropriate method of administration, the amount of each dose administered, and the specific interval between administrations of the active compound will depend on the specific active compound used, the condition of the patient or subject being treated, and the nature and severity of the disorder or condition being treated. Preferably, the active compound is administered in an amount and at an interval that will result in the desired treatment or improvement of the disorder or condition being treated.

[0062] The active compounds described herein can also be used in combination with sunscreens (UVA or UVB blockers, absorbers, diffusing agents) to prevent or protect against sun or UV induced skin damage.

[0063] In some variations, the composition further comprises ascorbic acid, its derivatives, and ascorbic acid-based products (such as magnesium ascorbate) or other products with antioxidant mechanisms (such as resveratrol, tocopherol, tocotrienols and derivatives).

[0064] In some variations, the composition further comprises a soybean extract, which is a mixture of compounds isolated from soybeans.Soybean extract can comprise only a portion of soybeans (e.g., extracts of soybeans such as low-fat soybean powder or filtered soybean milk) or can comprise the whole soybean (e.g., ground soybean powder).Soybean extract can be in the form of a fluid (e.g., soybean milk) or a solid (e.g., soybean powder or soybean milk powder).

[0065] The appropriate dosing regimen, the amount of each dose administered, and the specific interval between administration of each active topical skin benefit agent will depend on the particular combination of active agents used, the condition of the subject requiring treatment, and the nature and severity of the subject's local cosmetic condition.

[0066] In the cosmetic compositions provided herein, the concentration of the active compound is generally from 0.01% to 10%, or from about 0.01% to about 10%, for example, from 0.1% to 5%, or from about 0.1% to about 5%, or from 0.1% to 2%, or from about 0.1% to about 2%, or from 0.1% to 1%, or from about 0.1% to about 1%, based on the total weight of the composition.

[0067] The compositions described herein can be applied directly to the skin. Alternatively, they can be delivered by various transdermal delivery systems, such as transdermal patches, known in the art. For example, for topical administration, the active ingredient can be formulated in a cosmetically acceptable form by methods known in the art, such as solutions, gels, lotions, ointments, creams, suspensions, pastes, paints, powders, tinctures, aerosols, patches, and the like. The compositions can be in any of a variety of forms common in the cosmetic art for topical application to animals or humans, such as solutions, lotions, sprays, creams, ointments, salves, gels, and the like, as described below. Exemplary agents are those that are sufficiently viscous to remain on the area to be treated, that do not evaporate easily, and / or that are easily removed by washing with water, optionally with the aid of soap, cleanser, and / or shampoo.

[0068] The compositions can be made in a wide variety of product forms, including, but not limited to, solutions, suspensions, lotions, creams, gels, toners, sticks, sprays, ointments, cleansing washes and solid bars, shampoos and hair conditioners, pastes, foams, powders, mousses, shaving creams, wipes, strips, patches, powered patches, wound dressings and adhesive dressings, hydrogels, film-forming products, facial and skin masks, makeup products such as foundations, eyeliners and eyeshadows, etc. These product forms can include several types of cosmetically acceptable carriers, including, but not limited to, solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, solids and liposomes.

[0069] Cosmetically acceptable vehicle The cosmetically acceptable vehicle may act as a diluent, dispersant or carrier for the skin benefit ingredients in the composition so as to facilitate their distribution when the composition is applied to the skin.

[0070] The vehicle can be aqueous, anhydrous or an emulsion. Preferably, the composition is aqueous or an emulsion, particularly a water-in-oil or oil-in-water emulsion, preferentially an oil-in-water emulsion. When water is present, it will be in an amount that can range from 5 to 99% by weight, preferably 20 to 70% by weight, optimally 40 to 70% by weight.

[0071] In addition to water, relatively volatile solvents may also function as carriers in the compositions of the present invention. Most preferred are monohydric C1-C3 alkanols. These include ethyl alcohol, methyl alcohol and isopropyl alcohol. The amount of monohydric alkanol may range from 1 to 70%, preferably from 10 to 50%, optimally from 15 to 40% by weight.

[0072] Emollients may also serve as cosmetically acceptable carriers. These may be in the form of silicone oils and synthetic esters. The amount of emollient may range from 0.1 to 50% by weight, preferably from 1 to 20% by weight.

[0073] Silicone oils can be divided into volatile and non-volatile varieties. The term "volatile" as used herein refers to materials that have a measurable vapor pressure at ambient temperature. Volatile silicone oils are preferably selected from cyclic or linear polydimethylsiloxanes containing 3 to 9, preferably 4 to 5, silicon atoms. Linear volatile silicone materials generally have a viscosity of less than about 5 centistokes at 25°C, while cyclic materials typically have a viscosity of less than about 10 centistokes. Non-volatile silicone oils useful as emollients include polyalkylsiloxanes, polyalkylarylsiloxanes, and polyethersiloxane copolymers. Essentially non-volatile polyalkylsiloxanes useful herein include, for example, polydimethylsiloxanes having a viscosity of about 500 to about 25 million centistokes at 25°C. Among the preferred non-volatile emollients useful in the present compositions are polydimethylsiloxanes having a viscosity of about 10 to about 400 centistokes at 25°C.

[0074] Ester emollients include: (1) Alkyl esters or alkyl esters of fatty acids having 10 to 20 carbon atoms. Examples thereof include isoarachidyl neopentanoate, isononyl isonanonoate, oleyl myristate, oleyl stearate, and oleyl oleate. (2) Ether esters such as fatty acid esters of ethoxylated fatty alcohols. (3) Polyhydric alcohol esters. Ethylene glycol mono- and di-fatty acid esters, diethylene glycol mono- and di-fatty acid esters, polyethylene glycol (200-6000) mono- and di-fatty acid esters, propylene glycol mono- and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 monostearate, ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters, polyglycerol polyfatty acid esters, ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol distearate, polyoxyethylene polyol fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters are sufficient polyhydric alcohol esters. (4) Wax esters such as beeswax, spermaceti, myristyl myristate, stearyl stearate, and arachidyl behenate. (5) Sterol esters, of which cholesterol fatty acid esters are an example.

[0075] Fatty acids having from 10 to 30 carbon atoms may also be included as cosmetically acceptable carriers for the compositions of the present invention. Examples of this category are pelargonic acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, hydroxystearic acid, oleic acid, linoleic acid, ricinoleic acid, arachidic acid, behenic acid, and erucic acid.

[0076] Moisturizing agents of the polyhydric alcohol type may also be used as cosmetically acceptable carriers in the compositions of the present invention. Moisturizing agents help to enhance the effectiveness of emollients, reduce skin dryness, and improve skin feel. Representative polyhydric alcohols include glycerol, polyalkylene glycols, more preferably alkylene polyols and their derivatives, such as propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and their derivatives, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, 1,2,6-hexanetriol, ethoxylated glycerol, propoxylated glycerol, and mixtures thereof. The amount of humectant may range from 0.5 to 30% by weight of the composition, preferably from 1 to 15% by weight.

[0077] Thickeners may also be utilized as part of the cosmetically acceptable carrier of the compositions according to the present invention. Representative thickeners include crosslinked acrylates (e.g., Carbopol 982), hydrophobically modified acrylates (e.g., Carbopol 1382), cellulose derivatives, and natural gums. Among the useful cellulose derivatives are sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, ethylcellulose, and hydroxymethylcellulose. Natural gums suitable for the present invention include guar, xanthan, sclerotium, carrageenan, pectin, and combinations of these gums. The amount of thickener may range from 0.0001 to 5% by weight, usually from 0.001 to 1% by weight, and optimally from 0.01 to 0.5% by weight.

[0078] Collectively, the water, solvents, silicones, esters, fatty acids, humectants and / or thickeners will constitute the cosmetically acceptable carrier in an amount of from 1 to 99.9% by weight, preferably from 80 to 99% by weight.

[0079] The oil or oily material may be present together with the emulsifier to provide either a water-in-oil emulsion or an oil-in-water emulsion, depending largely on the average hydrophilic-lipophilic balance (HLB) of the emulsifier used.

[0080] Surfactants may also be present in the cosmetic compositions of the present invention. For leave-on products, the total surfactant concentration will range from 0.1 to 40%, preferably 1 to 20%, optimally 1 to 5% by weight of the composition. For wash-off products such as cleansers and soaps, the total surfactant concentration will range from about 1 to about 90%. The surfactant may be selected from the group consisting of anionic, nonionic, cationic and amphoteric actives. Particularly preferred nonionic surfactants are C4H4O condensed with 2 to 100 moles of ethylene oxide or propylene oxide per mole of hydrophobe. 10 -C 20 Fatty alcohol or acidic hydrophobe; C2-C condensed with 2 to 20 moles of alkylene oxide 10 Alkylphenols;Mono- and di-fatty acid esters of ethylene glycol;Fatty acid monoglycerides;Sorbitan, mono- and di-C8-C 20 block copolymers (ethylene oxide / propylene oxide); and polyoxyethylene sorbitan, as well as combinations thereof.Alkyl polyglycosides and saccharide fatty amides (e.g., methyl gluconamide) are also suitable nonionic surfactants.

[0081] Preferred anionic surfactants include soaps, alkyl ether sulfates and sulfonates, alkyl sulfates and sulfonates, alkyl benzene sulfonates, alkyl and dialkyl sulfosuccinates, C8-C 20 Acyl isethionates, acyl glutamates, C8-C 20 Alkyl ether phosphates and combinations thereof.

[0082] The cosmetic composition of the present invention may include a lathering surfactant. By "lathering surfactant" is meant a surfactant that produces a foam or lather when combined with water and mechanically agitated. Preferably, the lathering surfactant should be mild, meaning that it must provide sufficient cleansing or detergent benefits but not overly dry the skin and still meet the lathering criteria above. The cosmetic composition of the present invention may include a lathering surfactant at a concentration of about 0.01% to about 50%.

[0083] The composition can be formulated as a solution. The solution typically contains an aqueous or organic solvent, for example, about 50% to about 99.99% or about 90% to about 99% cosmetically acceptable aqueous or organic solvent. Examples of suitable organic solvents include propylene glycol, polyethylene glycol (200-600), polypropylene glycol (425-2025), glycerol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol, and mixtures thereof. One example of such a solvent is a mixture of ethanol / polyethylene glycol (80 / 20).

[0084] From such a solution, a lotion can be made, which typically contains about 1% to about 20% (e.g., about 5% to about 10%) of an emollient and about 50% to about 90% (e.g., about 60% to about 80%) of water.

[0085] Another type of product that can be formulated from a solution is a cream. A cream typically contains about 5% to about 50% (e.g., about 10% to about 20%) of an emollient and about 45% to about 85% (e.g., about 50% to about 75%) of water. Yet another type of product that can be formulated from a solution is an ointment. An ointment can contain a simple base of animal, vegetable or synthetic oils, or semi-solid hydrocarbons. An ointment can contain about 2% to about 10% of an emollient and about 0.1% to about 2% of a thickening agent. Examples of thickening agents include, but are not limited to, those listed in the International Cosmetic Ingredient Dictionary and Handbook, pp. 1693-1697.

[0086] The compositions described herein can also be formulated as emulsions. When the carrier is an emulsion, about 1% to about 10% (e.g., about 2% to about 5%) of the carrier comprises an emulsifier. The emulsifier can be nonionic, anionic, or cationic. Examples of emulsifiers include, but are not limited to, those described in ICI Handbook, pp.1673-1686.

[0087] Lotions and creams can be formulated as emulsions. Typically, such lotions contain 0.5% to about 5% emulsifier, while such creams typically contain about 1% to about 20% (e.g., about 5% to about 10%) emollient, about 20% to about 80% (e.g., 30% to about 70%) water, and about 1% to about 10% (e.g., about 2% to about 5%) emulsifier.

[0088] Single emulsion skin care formulations, such as oil-in-water and water-in-oil lotions and creams, are known in the art and are useful in the compositions and methods described herein.Multi-phase emulsion compositions, such as water-in-oil-in-water or oil-in-water-in-oil, are also useful in the compositions and methods described herein.In general, such single or multi-phase emulsions include water, emollients, and emulsifiers as essential components.

[0089] The compositions described herein can also be formulated as gels (e.g., aqueous, alcohol, alcohol / water, or oil gels using a suitable gelling agent). Suitable gelling agents for aqueous and / or alcoholic gels include, but are not limited to, natural gums, acrylic acid and acrylate polymers and copolymers, and cellulose derivatives (e.g., hydroxymethylcellulose and hydroxypropylcellulose). Suitable gelling agents for oils (e.g., mineral oil) include, but are not limited to, hydrogenated butylene / ethylene / styrene copolymers and hydrogenated ethylene / propylene / styrene copolymers. Such gels typically contain about 0.1% to 5% by weight of such gelling agents.

[0090] One or more additional agents may be added to the topical formulation to enhance percutaneous absorption of the active ingredient, including, but not limited to, dimethylsulfoxide, dimethylacetamide, dimethylformamide, surfactants, Azone (laurocapram), alcohol, acetone, propylene glycol, and polyethylene glycol. Physical methods may also be used to enhance percutaneous penetration, such as iontophoresis or sonophoresis.

[0091] The topical compositions provided herein comprise a cosmetically active agent having a desired effect on the skin as described herein, and any necessary ingredients for use as a carrier, e.g., an emulsion, cream, ointment, aqueous solution, lotion, or aerosol.

[0092] Carriers utilized in the compositions described herein can be in a wide variety of forms. These include emulsion carriers such as, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions, creams, ointments, aqueous solutions, lotions, or aerosols. A given component will distribute primarily in either the water or oil / silicone phase, depending on the water solubility / dispersibility of the component in the composition.

[0093] The skin formulations provided herein can typically include derivatives of any of the compounds or compositions described herein, and optionally a polar solvent. Solvents suitable for use in the formulations described herein include any polar solvent capable of dissolving the derivative. Suitable polar solvents can include water; alcohols (such as ethanol, propyl alcohol, isopropyl alcohol, hexanol, benzyl alcohol, etc.); polyhydric alcohols (such as propylene glycol, polypropylene glycol, butylene glycol, hexylene glycol, maltitol, sorbitol, glycerin, etc.); panthenol dissolved in glycerin, flavor oils, and mixtures thereof. Mixtures of these solvents can also be used. Exemplary polar solvents can be polyhydric alcohols and water. Mixtures of these solvents can also be used. Exemplary polar solvents can be polyhydric alcohols and water. Exemplary solvents can include glycerin, panthenol in glycerin, glycols such as propylene glycol and butylene glycol, polyethylene glycol, water, and mixtures thereof. Further polar solvents used can be alcohol, glycerin, panthenol, propylene glycol, butylene glycol, hexylene glycol and mixtures thereof.

[0094] Emollients may also be added to the cosmetic / dermatological compositions described herein. Emollients may include fats, oils, fatty alcohols, fatty acids, and esters, which aid application and adhesion, produce shine, and provide occlusive moisturization. Emollients suitable for use include isostearic acid derivatives, isopropyl palmitate, lanolin oil, diisopropyl dimerate, maleated soybean oil, octyl palmitate, isopropyl isostearate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, and glyceryl glycerides. The emollient may be glyceryl stearate, isopropyl linoleate, pentaerythrityl tetrastearate, neopentyl glycol dicaprylate / dicaprate, hydrogenated cocoglycerides, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, cetyl alcohol, octyldodecanol, oleyl alcohol, panthenol, lanolin alcohol, linoleic acid, linolenic acid, sucrose esters of fatty acids, octyl hydroxystearate, and mixtures thereof. Suitable emollients may include polar emollient emulsifiers (such as linear or branched polyglycerol esters) and non-polar emollients. The emollient component may typically comprise about 1% to about 90%, preferably about 10% to about 80%, more preferably about 20% to about 70%, and most preferably about 40% to about 60% of the cosmetic composition.

[0095] As used herein, "polar emollient" refers to an emollient emulsifier having at least one polar moiety, where the solubility of the cytoprotective derivative compound in the polar emollient (at 30° C.) is greater than about 1.5%, preferably greater than 2%, and more preferably greater than about 3%. Suitable polar emollients can include, but are not limited to, polyol esters and polyol ethers, such as linear or branched polyglycerol esters and polyglycerol ethers. Non-limiting examples of such emollients can include PG3 diisostearate, polyglyceryl-2-sesquiisostearate, polyglyceryl-5-distearate, polyglyceryl-10-distearate, polyglyceryl-10-diisostearate, acetylated monoglycerides, glycerol esters, glycerol tricaprylate / caprate, glyceryl ricinoleate, glyceryl isostearate, glyceryl myristate, glyceryl linoleate, polyalkylene glycols such as PEG600, monoglycerides, 2-monolaurin, sorbitan esters, and mixtures thereof.

[0096] As used herein, "non-polar emollient" refers to any emollient emulsifier that has no or minimal permanent electric moment. Suitable non-polar emollients may include, but are not limited to, esters and straight or branched chain hydrocarbons. Non-limiting examples of such emollients include isononyl isononanoate, isopropyl isostearate, octyl hydroxystearate, diisopropyl dimerate, lanolin oil, octyl palmitate, isopropyl palmitate, paraffin, isoparaffin, acetylated lanolin, sucrose fatty acid esters, isopropyl myristate, isopropyl stearate, mineral oil, silicone oil, dimethicone, allantoin, isohexadecane, isododecane, petrolatum, and mixtures thereof. The solubility of a compound in a polar or non-polar emollient can be determined according to methods known in the art.

[0097] Suitable oils include esters, triglycerides, hydrocarbons, and silicones. They can be a single material or a mixture of one or more materials. They may typically contain from 0.1% to about 100%, preferably from about 5% to about 90%, and most preferably from about 70% to about 90% of an emollient component.

[0098] Suitable oils for use herein include acetyl glycerides of alcohols and polyhydric alcohols, octanoates and decanoates, such as those of glycol and glycerol, ricinoleic acid esters of alcohols and polyhydric alcohols, such as cetyl ricinoleate, PG-3 diisostearate, polyglycerol ethers, polyglycerol esters, caprylic triglycerides, capric triglycerides, isostearic acid triglycerides, adipic triglycerides, phenyl triglycerides, glycerol esters ... It can be methicone, lanolin oil, polybutene, isopropyl palmitate, isopropyl isostearate, cetyl ricinoleate, octyldodecanol, oleyl alcohol, hydrogenated vegetable oils, castor oil, modified lanolin, octyl palmitate, lanolin oil, maleated soybean oil, cetyl ricinoleate, glyceryl trioctanoate, diisopropyl dimerate, synthetic lanolin derivatives and branched alcohols, sucrose esters of fatty acids, octyl hydroxystearate and mixtures thereof.

[0099] Preferably, the oils used can be selected so that the majority (at least about 75%, preferably at least about 80%, and most preferably at least about 99%) of the oil types used have solubility parameters that do not differ by more than about 1 to about 0.1, preferably less than about 0.8 to about 0.1.

[0100] Surfactants may also be added to the compositions described herein to impart beneficial cosmetic or application properties. Surfactants suitable for use may be those capable of forming emulsions and / or association structures. Surfactant emulsifiers may comprise from 0% to about 20%, preferably from 0% to about 15%, and most preferably from about 1% to about 10% of the formulation.

[0101] Examples of surfactants that can be used in the compositions described herein include sodium alkyl sulfates, such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acylsarcosinates, such as sodium N-lauroyl sarcosinate and sodium N-myristoyl sarcosinate, sodium dodecylbenzenesulfonate, hydrogenated sodium coconut monoglyceride sulfate, sodium lauryl sulfoacetate and N-acyl glutamate, such as N-palmitoyl glutamate, sodium N-methylacyltaurate, sodium N-methylacylalanine, sodium α-olefinsulfonate and sodium dioctyl sulfosuccinate; N-alkylaminoglycerols, such as N-lauryl-diamino-ethylglycerol; and N-myristyldiaminoethyl glycerol, N-alkyl-N-carboxymethyl ammonium betaine and sodium 2-alkyl-1-hydroxyethyl imidazoline betaine; polyoxyethylene alkyl ethers, polyoxyethylene alkylaryl ethers, polyoxyethylene lanolin alcohols, polyoxyethylene glyceryl mono fatty acid esters, polyoxyethylene sorbitol fatty acid esters, polyoxyethylene fatty acid esters, higher fatty acid glycerol esters, sorbitan fatty acid esters, Pluronic® type surfactants, and polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monooleate and polyoxyethylene sorbitan monolaurate. Emulsifier-type surfactants known to those skilled in the art can be used in the compositions described herein.

[0102] Surfactants that form association structures, preferably lamellar or hexagonal liquid crystals, at ambient temperature when mixed with a polar solvent may also be useful herein. When preparing sample combinations of surfactant and polar solvent to demonstrate the ability to form association structures, the surfactant must be sufficiently soluble in the polar solvent so that association structures can form at ambient temperature.

[0103] Any surfactant that forms an association structure at ambient temperature and is suitable for use in cosmetics may be suitable for use herein. Surfactants suitable for use in cosmetics pose no or minimal dermatological or toxicological problems. Anionic surfactants, nonionic surfactants, cationic surfactants, amphoteric surfactants and mixtures thereof may be suitable for use.

[0104] The surfactant can be used at a level of about 4% to about 97%, preferably about 5% to about 95%, more preferably about 20% to about 90%, and most preferably about 30% to about 70% of the association structure.

[0105] The cosmetic compositions described herein may include one or more materials, referred to herein singly or collectively as "solidifying agents," that are effective in solidifying certain liquid-based materials used in the cosmetic compositions (as used herein, the term "solidifying" refers to the physical and / or chemical changes of a liquid-based material to form a solid or semi-solid at ambient conditions, i.e., to form a final composition that has a stable physical structure and can be deposited on the skin under normal use conditions). As will be appreciated by those skilled in the art, the selection of a particular solidifying agent for use in a cosmetic composition will depend on the particular type of composition desired, i.e., gel or wax-based, the desired rheology, the liquid-based material used, and other materials used in the composition. The solidifying agent may be present at a concentration of preferably about 0.1% to about 90%, more preferably about 1% to about 50%, even more preferably about 5% to about 40%, and most preferably about 3% to about 20%.

[0106] The wax cosmetic stick forms provided herein may preferably contain about 5% to about 50% (by weight) of a waxy solidifying agent. As used herein, the term "waxy solidifying agent" refers to a solidifying material having wax-like properties. Such waxy materials may also serve as emollients. Among the waxy materials useful herein are high melting point waxes, i.e., waxes having a melting point of about 65°C to about 125°C, such as beeswax, spermaceti, carnauba, bayberry, candelilla, montan, ozokerite, ceresin, paraffin, synthetic waxes such as Fischer-Tropsch wax, microcrystalline wax, and mixtures thereof. Among those useful herein are ceresin, ozokerite, white beeswax, synthetic waxes, and mixtures thereof. Low melting point waxes having a melting point of about 37°C to about 75°C may be preferred for use in the wax stick forms described herein. Wax sticks containing volatile silicone oil as the liquid base material preferably contain about 10% to about 35%, more preferably about 10% to about 20% (by weight) of a low melting point wax. Such materials include fatty acids, fatty alcohols, fatty acid esters and fatty acid amides having a fatty chain of about 8 to about 30 carbon atoms, and mixtures thereof. Wax-like materials include cetyl alcohol, palmitic acid, stearyl alcohol, behenic acid amide, sucrose esters of tallow fatty acids, mono- and di-fatty acid esters of polyethylene glycol, and mixtures thereof. Stearyl alcohol, cetyl alcohol, and mixtures thereof are primarily used. Additional fatty acids, fatty alcohols, and other wax-like materials are also known in the art.

[0107] Additionally, these compositions may include other cosmetic agents, carriers, adjuvants, etc. Some specific additives may include sunscreens, retinoids, antioxidants, hydroxy acids, acceptable non-toxic metal salts of fatty acids, natural amino acids, or hydroxyalkyl acids, botanical extracts, salicylic acid, benzoyl peroxide, antibiotics, antiandrogens, anti-inflammatory agents, antioxidants, ascorbic acid, vitamin B, tocopherols or tocotrienols, corticosteroids, moisturizers, surfactants, keratolytic agents, complexing agents, colorants, fragrances, and mixtures thereof.

[0108] Synthesis method The resorcinol compounds described herein can be synthesized by an appropriate combination of generally well-known synthetic methods. Techniques useful for synthesizing the compounds herein will be readily apparent in light of the disclosure herein and are available to those of skill in the relevant art. 4-Alkylresorcinols are commercially available from Sigma-Aldrich, St. Louis, Missouri, USA.

[0109] Working Example Example 1 Evaluation of signs of decomposition and stabilization of 4-alkylresorcinols Measuring color Samples for color evaluation were prepared by dissolving 4-hexylresorcinol (200 mg) or 4-ethylresorcinol (200 mg) in DI water:butylene glycol (4:1; 20 mL) to produce a clear, colorless homogenous solution. A portion (5 mL) of each solution was added to a 20 mL scintillation vial containing either nicotinamide (B3) (50 mg), AceMet (acetyl methionine) (50 mg), or B3 (50 mg) + AceMet (50 mg) and monitored at room temperature (approximately 20-22 °C). After 2 weeks, the color of each solution was evaluated by eye and experimentally L*a*b* measurements were determined using a Labscan XE instrument (Hunter Associates Labs Inc., Reston, VA) and processed with Universal Software (version 4.10). The L* parameter measures darkness and lightness and ranges from black (L*=0) to white (L*=100). The a* parameter measures color content and intensity, ranging from green (a*<0) to neutral gray (a=0) to red (a*>0). The b* parameter also measures color content and intensity, ranging from blue (b*<0) to neutral gray (b*=0) to yellow (b*>0).

[0110] Determination of 4-alkylresorcinols The amount of 4-alkylresorcinols present in each sample used for color measurement was quantified by high performance liquid chromatography (HPLC) after 2 weeks at room temperature (approximately 20-22 °C). Aliquots (100 μL) from each color measurement solution were diluted with DI water:acetonitrile (1:1, 900 μL) to obtain test samples (1 mL). Aliquots (10 μL) from each test sample were injected into a Waters 2695 Separations Module and chromatographed and separated on a Restek Pinnacle DB C18 (5 μm, 4.6 × 150 mm) column operated at 30 °C, and 4-alkylresorcinols were monitored using a Waters 2996 Photodiode Array Detector set at 281 nm. The mobile phase consisted of water (A) and acetonitrile (B) with a gradient from 95:5 (A:B) to 5:95 (A:B) within 20 min at a flow rate of 1 mL / min, followed by an isocratic elution of 5:95 (A:B) for 3 min, to achieve optimal separation. Chromatographic data were processed using Empower 2 software (Waters Corporation, Milford, MA). Standard control samples of 4-alkylresorcinols at 1x, 5x, and 1 / 5 concentrations were freshly prepared and analyzed immediately. A standard curve was constructed within the test sample range to confirm linearity.

[0111] All samples were analyzed in duplicate and the average value reported. The amount of 4-alkylresorcinol present in each test sample after two weeks was determined by measuring the chromatographic peak area under the curve at 281 nm for 4-alkylresorcinol and expressed as a percentage of the corresponding chromatographic peak area under the curve at 281 nm for a freshly prepared control sample.

[0112] Table 1 below shows the effect of AceMet on the color and stability of 4-alkylresorcinols (hexylresorcinol "HR" and ethylresorcinol "ER") in the presence and absence of nicotinamide "B3". Freshly prepared solutions of HR are colorless and no degradation of HR is observed by HPLC analysis. After 2 weeks, the color of the HR solution changes to a reddish pink, as indicated by an increase in a* and b* components (and a decrease in L*) and a 40% decrease in HR levels. Addition of B3 to the HR solution greatly accelerates the degradation of HR to 55% degradation and produces more intense color, as indicated by an even greater increase in a*, b*, and a decrease in L*. In contrast and unexpectedly, the addition of AceMet to the HR solution significantly prevents color formation and HR degradation in the presence or absence of B3, as indicated by the corresponding L*a*b* values ​​and HR contents that are very close to control levels. Similarly, AceMet significantly prevented color development in ER solutions in the presence or absence of B3 and provided protection against ER degradation, albeit to a lesser extent compared to HR. These results clearly demonstrate the significant effect of AceMet on the color and chemical stabilization of 4-alkylresorcinols in the presence or absence of other cosmetic ingredients (such as B3) that may further accelerate such color formation and degradation.

[0113] The effect of AceMet on the color and stability of 4-alkylresorcinols (HR and ER) in the presence and absence of B3 after two weeks at room temperature (approximately 20-22° C.) is shown in the table below.

[0114] [Table 1]

[0115] Example 2. ER and AceMet A topical cosmetic composition within the scope of the present invention was prepared.

[0116] The base formulation shown in the table below was made by heating the ingredients in Phase A with stirring to 70-85°C. The ingredients in Phase B were heated in a separate vessel with stirring to 70-85°C. Phase A was then added to Phase B while maintaining both phases at 70-85°C. The resulting mixture was stirred at 70-85°C for at least 15 minutes and then cooled. The ingredients in Phase C were added at 50°C, followed by the ingredients in Phase D at 40°C.

[0117] Table 2. Basic formulations [Table 2]

[0118] Example 3 Additional cosmetic compositions within the scope of the present invention were prepared as shown in the table below.

[0119] Table 3 [Table 3] TIFF0007608424000011.tif121149

[0120] The composition was prepared as follows. 1. Heat Phase A to 80°C while mixing. 2. In a separate container, heat Phase B to 75°C while mixing. 3. Add B to A and mix for 15 minutes while maintaining the temperature at 70-80°C, then turn off the heat and continue mixing for an additional 15 minutes. 4. At 50°C add Phase C and mix for 10 minutes. 5. At 40°C add Phase D and mix for 10 minutes.

[0121] Examples 4 to 11 A series of additional compositions within the scope of the present invention were prepared according to the method of Example 2 and are listed in the table below.

[0122] Table 4. HR and AceMet [Table 4]

[0123] Example 12 The formulations in the table below were prepared according to the methods described in Example 1 above.

[0124] Table 5: Formulations for skin lotions [Table 5] TIFF0007608424000014.tif46166

Claims

1. a. 0.00001-10% N-acetylmethionine; b. 0.00001 to 10% of one or more 4-substituted resorcinol derivatives of formula I 【Chemistry 1】 [In the formula, each R １ and R ２ are independently a hydrogen atom, -CO-R, -COO-R, or CONHR, １ -C １８ represents a hydrocarbon; and R 3 is ethyl; and c. A cosmetically acceptable vehicle Including, A topical cosmetic composition, wherein the 4-substituted resorcinol derivative is stabilized in the composition by the N-acetylmethionine.

2. R １ and R ２ The composition of claim 1 , wherein both of are H.

3. 3. The composition of claim 1 or 2, wherein the 4-substituted resorcinol derivative of formula I is selected from the group consisting of 4-ethylresorcinol, 4-isopropylresorcinol, 4-hexylresorcinol, 4-cyclohexylresorcinol, and mixtures thereof, or cosmetically acceptable salts thereof.

4. 4. The cosmetic composition of any one of claims 1 to 3, further comprising a skin benefit agent selected from the group consisting of alpha hydroxy acids and esters, beta hydroxy acids and esters, polyhydroxy acids and esters, kojic acid and esters, ferulic acid and esters, vanillic acid and esters, diacids and esters, retinol, retinal, retinyl esters, hydroquinone, t-butyl hydroquinone, 1-methylnicotinamide chloride, and mixtures thereof.

5. a. 4-substituted resorcinol derivatives stabilized by N-acetylmethionine; b. any skin benefit agent; and c. a cosmetically acceptable vehicle; A stabilized cosmetic composition comprising: N-acetylmethionine present in an amount of 0.0001% to 5% by weight of said cosmetic composition; the weight ratio of said N-acetylmethionine to said 4-substituted resorcinol derivative is from 10,000:1 to 1:100,000; The 4-substituted resorcinol derivative is represented by the following general formula I 【Chemistry 1】 wherein each R 1 and R 2 is independently selected from the group consisting of a hydrogen atom, -CO-R, -COO-R, and CONHR, where R represents a C 1 -C 18 hydrocarbon, and R 3 is ethyl.

6. 1. A method for stabilizing 4-ethylresorcinol or 4-hexylresorcinol in a composition comprising a cosmetically acceptable vehicle by adding acetylmethionine to the composition in an amount sufficient to stabilize said 4-ethylresorcinol or said 4-hexylresorcinol.

7. 4. Use of N-acetylmethionine and a 4-substituted resorcinol derivative according to any one of claims 1 to 3 in the manufacture of a topical cosmetic composition.

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