Stabilization of resorcinol compounds in cosmetic compositions

Abstract

Topical cosmetic compositions containing 4-substituted resorcinol derivatives in combination with N-acetylmethionine exhibit improved storage stability and oxidative stability. A method of 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. The invention relates to the use of N-acetylmethionine and stabilized 4-substituted resorcinol derivatives in the manufacture of topical cosmetic compositions.

Description

[0001] This application is a divisional application of application No. 202080050769.8, filed on June 23, 2020, and entitled “Stabilization of resorcinol compounds in cosmetic compositions”. Technical Field

[0002] The present application provides topical cosmetic compositions containing 4-substituted resorcinol derivatives stabilized with acetylmethionine. Background Art

[0003] Beauty is in the eye of the beholder and is influenced by numerous physiological and genetic factors. The foundation of a natural-looking appearance as beauty lies in the skin, including the hair. Ideal skin should be smooth and even, with no noticeable surface imperfections other than a translucent appearance with even color distribution. Skin and hair problems in aging individuals may be caused by a variety of extrinsic or intrinsic factors, such as harmful UV radiation from the sun, exposure to the environment, stress, fatigue, illness, or a combination thereof.

[0004] Resorcinol (1,3-benzenediol) derivatives have been used to provide cosmetic benefits to the skin and hair. 4-substituted resorcinol derivatives and their preparations have been used for skin whitening and other cosmetic purposes; see, for example, U.S. Patent No. 4,959,393, U.S. Patent No. 6,132,740, U.S. Patent Application Publication No. 2008 / 0131382, and Japanese Published Patent Application Nos. JP 2001-01 0925 and JP 2000-327557. U.S. Patent Application Publication No. 2004 / 0042983 discloses resorcinol-based skin whitening agents that can be synthesized using coumarin as a starting material. However, some of these compounds may be difficult to formulate because they are unstable in cosmetically acceptable vehicles.

[0005] Oxidative instability is an undesirable property of 4-substituted resorcinols. Therefore, there is a need for an agent that stabilizes 4-substituted resorcinols against oxidation. In particular, there is a need for an agent that can prevent oxidation of 4-substituted resorcinols.

[0006] It would be desirable to have topical cosmetic compositions containing resorcinol derivatives that are stable to factors such as discoloration, oxidation, general storage stability, etc. Compositions comprising 4-alkylresorcinols stabilized with N-acetylmethionine (AceMet) described herein meet this need. Summary of the invention

[0007] a. about 0.00001 to about 10% N-acetylmethionine,

[0008] b. from about 0.00001 to about 10% of a 4-substituted resorcinol derivative,

[0009] and

[0010] c. Vehicle or carrier.

[0011] 4-Substituted resorcinol derivatives are stabilized against degradation / discoloration / oxidation by including N-acetylmethionine in the composition. The composition comprises a cosmetically effective amount of a resorcinol compound and an amount of N-acetylmethionine sufficient to stabilize the resorcinol compound against chemical degradation as evidenced by discoloration.

[0012] The resorcinol derivatives provided herein are defined below and can be used to treat or prevent one or more cosmetic conditions, such as preventing, alleviating, reducing or treating the signs or appearance of undesirable skin pigmentation affected by one or more conditions, as desired by a subject in need thereof.

[0013] The 4-substituted resorcinol derivatives have the general formula I:

[0014]

[0015] wherein each R1 and R2 are independently selected from hydrogen atom, -CO-R, -COO-R and CONHR; wherein R represents C1–C 18 hydrocarbon;

[0016] R3 represents C1–C 18 Hydrocarbon or having the general formula (II):

[0017]

[0018] Where X represents hydrogen; OR 1 , where R 1 represents hydrogen, (C1-C6)alkyl or aryl-(C1-C6)alkyl; OCOR 2 , where R 2 represents (C1-C6)alkyl, aryl-(C1-C6)alkyl or phenyl; (C1-C6)alkyl; aryl-(C1-C6)alkyl; or NHR 1 , where R 1 As defined above;

[0019] n is 0 to 3; and

[0020] Dashed lines represent optional double bonds;

[0021] And preferably include 4-linear alkyl resorcinol, 4-branched alkyl resorcinol, 4-cycloalkyl resorcinol and mixtures thereof.

[0022] More particularly preferred resorcinol derivatives include 4-ethylresorcinol, 4-isopropylresorcinol, 4-hexylresorcinol and 4-cyclohexylresorcinol, and O-acylated forms thereof.

[0023] In another embodiment, a stabilized cosmetic composition is provided, comprising:

[0024] a. 4-substituted resorcinol derivatives stabilized by N-acetylmethionine;

[0025] b. optional skin benefit agents; and

[0026] c. Cosmetically acceptable vehicles;

[0027] wherein the N-acetylmethionine is present in an amount from about 0.0001% to about 5% by weight of the cosmetic composition; and

[0028] The weight ratio of the N-acetylmethionine to the 4-substituted resorcinol derivative is about 10,000:1 to about 1:100,000.

[0029] The compositions of the present invention are aesthetically pleasing and the resorcinol derivatives therein have improved storage / color / oxidative stability.

[0030] Also provided is a method of stabilizing (against oxidation, discoloration, storage, etc.) 4-hexylresorcinol in a composition comprising a cosmetically acceptable vehicle by adding to the composition an amount of N-acetylmethionine sufficient to stabilize the 4-hexylresorcinol.

[0031] 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 thereof.

[0032] In another variation, the present application provides a method of regulating skin condition by topically applying to the skin of a subject in need thereof an effective amount of a composition of the present invention comprising a 4-substituted resorcinol derivative and N-acetylmethionine.

[0033] The present application also provides a product comprising instructions for instructing a user to apply a composition including a skin care composition, the skin care composition comprising one or more 4-substituted resorcinol derivatives, the composition further comprising N-acetylmethionine as a stabilizer. The composition may comprise a pharmaceutically and / or dermatologically acceptable carrier and vehicle.

[0034] The compositions of the present invention are aesthetically pleasing and have improved storage / oxidative stability. DETAILED DESCRIPTION OF THE INVENTION

[0036] definition

[0037] As used in this application, "subject" is a mammal, particularly a human. It should be understood that the use of "in" an individual may also include the use of "on" an individual; that is, depending on the context of use, the use of "in" an individual may include internal use, external use, or both.

[0038] As used herein, "applying to the skin in need of such treatment" means contacting (e.g., by using the hands or an applicator such as, but not limited to, a wipe, tube, roller, spray, or patch) an area of ​​skin in need of such treatment or an area of ​​skin near an area of ​​skin in need of such treatment.

[0039] As used herein, "composition" refers to compositions suitable for topical application to the skin.

[0040] As used herein, the term "cosmetic composition" means a composition for topical application to human skin, including leave-on and rinse-off products.

[0041] As used in this application, the term "skin" includes the skin on a person's face, neck, chest, back, arms, underarms, hands, legs, and scalp.

[0042] Except in the examples, or where otherwise explicitly indicated, all numbers in this specification indicating amounts of material or reaction conditions, physical properties of materials and / or use are to be understood as modified by the word “about.” Unless otherwise indicated, all amounts are by weight of the composition.

[0043] 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 do not have to be exhaustive.

[0044] For all compositions described herein and all methods of using the compositions described herein, the compositions may include the listed components or steps, or may consist "essentially of" the listed components or steps. When a composition is described as consisting "essentially of" the listed components, the composition includes the listed components and may include other components that do not substantially affect the skin or the skin condition being treated, but does not include any other components other than those explicitly listed that substantially affect the skin or the skin condition being treated; or, if the composition does include additional components other than those listed that significantly affect the skin or the skin condition being treated, the composition does not include the additional components in sufficient concentration or amount to significantly affect the skin or the skin condition being treated. When a method is described as consisting "essentially of" the listed steps, the method includes 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 those explicitly listed that significantly affect the skin or the skin condition being treated.

[0045] As used herein, the terms "cosmetically acceptable" or "dermatologically acceptable" mean that the compositions so described, or components thereof, are suitable for use in contact with the skin, especially human skin, without undue toxicity, incompatibility, instability, irritation, or allergic response.

[0046] As used herein, the terms "cosmetically acceptable carrier", "cosmetically acceptable excipient", "dermatologically acceptable carrier" or "dermatologically acceptable excipient" include all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, etc. that are cosmetically acceptable or dermatologically acceptable. Unless any conventional media or agents are incompatible with the active ingredient, their use in cosmetic compositions is considered. Supplementary active ingredients may also be incorporated into the composition. Cosmetically acceptable carriers are suitable for topical application to the skin, have good aesthetic properties, are compatible with the active agents and any other components described herein, and cause only minimal or no safety or toxicity issues. The safe and effective amount of the carrier is about 50% to about 99.99% or about 50% to about 99% of the composition, 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%. Percentages are preferably weight percentages.

[0047] As used herein, the terms "skin condition," "dermatologic condition," and "dermatological condition" are used interchangeably.

[0048] 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 oxide and zinc oxide; and skin protectants; or mixtures thereof.

[0049] As used herein, the term "topical application" refers to applying or spreading the composition described herein onto the surface of the skin.

[0050] As used herein, "alkyl" is intended to include a saturated straight or branched hydrocarbon chain having a specified number of carbon atoms. In one embodiment, an alkyl group may have 1 to 12 carbon atoms. "Alkylene" is intended to include a divalent saturated straight or branched hydrocarbon chain having a specified number of carbon atoms. In one embodiment, an alkylene group may have 1 to 12 carbon atoms.

[0051] As used herein, "cycloalkyl" is intended to include a saturated cyclic hydrocarbon chain having the specified number of carbon atoms. In one embodiment, a cycloalkyl group may have from 3 to 12 carbon atoms.

[0052] As used herein, "alkenyl" is intended to include straight or branched hydrocarbon chains having at least one carbon-carbon double bond. In one embodiment, an alkenyl group may have from 2 to 12 carbon atoms.

[0053] As used herein, "aryl" is intended to include aromatic hydrocarbons, such as substituted or unsubstituted phenyl or naphthyl.

[0054] Although the compounds described herein can appear as neutral (non-salt) compounds and can be used as neutral (non-salt) compounds, this specification is intended to include all salts of the compounds described herein, and methods using such salts of the compounds. In one embodiment, the salt of the compound includes pharmaceutically acceptable salts and / or dermatologically acceptable salts. Cosmetically acceptable salts are salts that can be applied to the skin of humans and / or animals, and retain at least some biological activities of free compounds (neutral compounds or non-salt compounds) when applied. The salt of the required alkaline compound can be prepared by treating the compound with acid by methods known to those skilled in the art. 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 acid and salicylic acid. Salts of alkaline compounds and 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 metal 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 salts, dibenzylamine salts, N-ethylpiperidinium salts, N,N-dibenzylethylenediamine salts, triethylamine salts or trialkylamine salts. Salts of acidic compounds with amino acids, such as lysine salts, can also be prepared.

[0055] Composition

[0056] 4-Substituted resorcinol derivatives

[0057] Resorcinol derivatives are known compounds and can be easily obtained, for example, by a method in which a saturated carboxylic acid and resorcinol are condensed in the presence of zinc chloride and the resulting condensate is reduced with zinc amalgam / hydrochloric acid (Lille. J. Bitter, LA. Peiner. V, Tr. Nauch-Issled. Inst. slantsev 1969, No. 18, 127); or by a method in which resorcinol and a corresponding alkyl alcohol are reacted at a high temperature of 200 to 400° C. in the presence of an alumina catalyst (British Patent 1581428).

[0058] The composition of the present invention comprises an effective amount of a resorcinol derivative of the following formula (I):

[0059]

[0060] Each R1 and R2 independently represents a hydrogen atom, -CO-R (acyl group), -COO-R, CONHR; the latter three are represented by the following formula A:

[0061]

[0062] Where R represents a saturated or unsaturated, linear, branched or cyclic C1–C 18 In a preferred embodiment, each or both of R1 and / or R2 represent hydrogen. In a more preferred embodiment, R1 and R2 both represent hydrogen.

[0063] R3 means:

[0064] (1) Saturated or unsaturated, linear, branched or cyclic C1–C 18 Hydrocarbons, preferably C2–C 12 hydrocarbon;

[0065] or

[0066] (2) Groups of general formula (II)

[0067]

[0068] Where X is hydrogen; OR 1 , where R 1 represents hydrogen, (C1-C6)alkyl or aryl-(C1-C6)alkyl; OCOR 2 , where R 2 represents (C1-C6)alkyl, aryl-(C1-C6)alkyl or phenyl; (C1-C6)alkyl; aryl-(C1-C6)alkyl; or NHR 1 , where R 1 As defined above;

[0069] wherein n is 0 to 3; and wherein the dashed line represents an optional double bond.

[0070] 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, the group is a 7-membered ring; when n is 3, the group is an 8-membered ring.

[0071] 4-Substituted resorcinol: linear or branched

[0072] In the above formula (1), the group represented by R3 and preferably having 2 to 12 carbon atoms, wherein the arrangement is straight-chain, can include ethyl, propyl, butyl, amyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl. These straight-chain alkyl groups can be substituted by methyl or ethyl at one or more hydrogen atoms thereof. Specific examples of substituted alkyl groups include isopropyl, isobutyl, isopentyl, 2-methylhexyl, etc. Preferred alkyl groups are those in which R3 is ethyl, propyl, isopropyl, butyl, amyl, hexyl, heptyl or octyl. The most preferred alkyl resorcinols are those in which R3 is ethyl, isopropyl or hexyl.

[0073] 4-Cycloalkylresorcinol

[0074] In the case of a resorcinol derivative of formula (I) in which R3 represents the structure of general formula (II) shown above, the resorcinol derivative is referred to herein as 4-cycloalkylresorcinol and is represented by the following general formula (III):

[0075]

[0076] In the general formula (III) (and formula (II) above):

[0077] X represents hydrogen; OR 1 , where R 1 represents hydrogen, (C1-C6)alkyl or aryl-(C1-C6)alkyl; OCOR 2 , where R 2 represents (C1-C6)alkyl, aryl-(C1-C6)alkyl or phenyl; (C1-C6)alkyl; aryl-(C1-C6)alkyl; or NHR 1 , where R 1 As defined above;

[0078] n is 0 to 3; and the dashed line represents an optional double bond at that position.

[0079] Examples of more specific embodiments of 4-cycloalkylresorcinol include:

[0080] (a) A compound of formula (III), wherein a single bond connects the two carbon atoms at the dashed line;

[0081] (b) a compound of formula (III), wherein n is 1;

[0082] (c) a compound of formula (III), wherein X is hydrogen;

[0083] (d) a compound of formula (III), wherein X is hydrogen, methyl or ethyl;

[0084] (e) a compound of formula (III), wherein n is 0;

[0085] (f) a compound of formula (III) wherein n is 2; and

[0086] (g) A compound of formula (III), wherein X is benzyloxy.

[0087] Preferred compounds of formula (III) are 4-cyclohexylresorcinol, 4-cycloheptylresorcinol and 4-cyclooctylresorcinol. The most preferred compound of formula (III) is 4-cyclohexylresorcinol.

[0088] The amount of the resorcinol derivative ranges from about 0.00001 to about 10 wt %, preferably from about 0.001 to about 7 wt %, and most preferably from about 0.01 to about 5 wt % of the total amount of the cosmetic composition.

[0089] N-acetyl amino acids

[0090] We have now found that N-acetyl amino acids inhibit the oxidation of 4-substituted resorcinol derivatives. Preferably, according to the present invention, N-acetyl amino acids are used to stabilize 4-substituted resorcinol incorporated into cosmetic compositions.

[0091] Acetylmethionine is the N-acetyl derivative of the amino acid methionine. N-acetylmethionine ("AceMet") is preferred and, for purposes of the present invention, has the following chemical structure:

[0092]

[0093] Acetylmethionine (CAS No. 1115-47-5 for acetyl-DL-methionine) and N-acetyl-L-methionine ("AceMet"), CAS No. 65-82-7, have been included in cosmetic applications. For the purposes of the present invention, N-acetyl-L-methionine ("AceMet") is preferred because of its enhanced solubility properties (water solubility, logP and logD) compared to L-methionine.

[0094] AceMet is a nutritional and metabolic equivalent form of the essential amino acid L-methionine (L-Met), which is used as an intermediate in the biosynthesis of S-adenosylmethionine (SAMe), an essential nutrient for maintaining optimal cellular energy balance, and many important biomolecules, including cysteine, carnitine, taurine, lecithin, phosphatidylcholine. AceMet has also been shown to have detoxification properties (e.g., an antidote for acetaminophen overdose, detoxification of benzene derivatives), and is speculated to be stable in formulations (WO 0040217, WO 05055947). N-acetylamino acids (e.g., AceMet) have been used as part of a combination of multiple active substances for topical cosmetic applications to treat skin diseases (related to aging, hair, nails, etc.) (WO 00 / 40717 of Tristrata Inc).

[0095] N-acetylmethionine is available from several suppliers including Sigma-Aldrich.

[0096] The compositions of the present invention typically 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 present invention is that the 4-substituted resorcinol can be stabilized against oxidation by AceMet.

[0097] The amount of AceMet effective to inhibit oxidation of the 4-substituted resorcinol derivative can be determined experimentally. 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.

[0098] 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%.

[0099] Optional components

[0100] Any of the compounds described herein may be mixed with other components. Examples of such components include oily components such as hydrocarbons, fats and oils such as liquid paraffin, squalene, petrolatum such as (a registered trademark of Conopco Corp., Englewood Cliffs, N.J., U.S.A.), cetyl alcohol, isostearyl alcohol, cetyl-2-ethylhexanoate, 2-octyldodecanol, glycerin, glyceryl triisostearate, nut oils and lanolin, as well as waxes, silicones, surfactants, thickeners, neutralizers, preservatives, bactericides, antioxidants, powder components, pigments, fragrances, ultraviolet light absorbers, drugs, metal sealants and pH adjusters.

[0101] Skin Benefit Agents

[0102] The cosmetic composition of the present invention can be used in personal care products and personal washing products, such as creams, soaps, deodorants, etc. When incorporated into a personal care composition, the N-acetylmethionine compound and stabilizer forming the composition of the present invention can have other useful functions.

[0103] Preferred personal care compositions are those suitable for application to human skin, which optionally but preferably include a skin benefit agent. Suitable skin benefit agents include anti-aging agents, wrinkle reducing agents, skin whitening agents, anti-acne agents, and sebum control 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 ferulic acid ester derivatives, vanillic acid and esters, diacids (such as sebacic acid and azelaic acid) and esters, retinol, retinal, retinyl esters, hydroquinone, tert-butyl hydroquinone, mulberry extract, licorice extract, 1-methylnicotinamide chloride, and resorcinol derivatives other than the 4-substituted resorcinol derivatives discussed above.

[0104] The active compounds described herein may also be used in combination with skin peeling agents (including glycolic acid or trichloroacetic acid facial peels) or skin exfoliants (including retinoids, such as retinoic acid or retinol) to lighten skin color and prevent pigment regeneration. The appropriate dosing regimen, the amount of each dose administered, and the specific intervals between administrations of the active compound may 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 interval that results in the desired treatment or improvement of the disorder or condition being treated.

[0105] The active compounds described herein may also be used in combination with sunscreens (UVA or UVB blockers, absorbers, diffusers) to prevent or protect from sunlight or UV-induced skin damage.

[0106] 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, tocopherols, tocotrienols and derivatives).

[0107] In some variations, the composition further comprises a soybean extract, which is a blend of compounds isolated from soybeans. The soybean extract may comprise only a portion of soybeans (e.g., an extract of soybeans, such as lipid-reducing soybean flour or filtered soybean milk), or may comprise the entire soybean (e.g., ground soybean powder). The soybean extract may be in the form of a fluid (e.g., soybean milk) or a solid (e.g., soybean flour or soybean milk powder).

[0108] The appropriate dosing regimen, the amount of each dose applied, and the specific intervals between administrations of each active topical skin benefit agent may depend on the specific combination of active agents used, the condition of the subject in need thereof, and the nature and severity of the subject's topical cosmetic condition.

[0109] In the cosmetic compositions provided herein, the concentration of the active compound is generally between 0.01% and 10% or between about 0.01% and about 10%, for example, between 0.1% and 5% or between about 0.1% and about 5%, or between 0.1% and 2% or between about 0.1% and about 2%, or between 0.1% and 1% or between about 0.1% and about 1%, relative to the total weight of the composition.

[0110] Compositions described herein can be directly applied to skin. Alternatively, they can be delivered by various transdermal delivery systems, such as transdermal patches known in the art. For example, for topical application, active ingredient can be formulated into solution, gel, emulsion, ointment, cream, suspension, paste, liniment, powder, tincture, aerosol, patch, etc. in cosmetically acceptable form by methods known in the art. Described composition can be any one of the multiple forms commonly used for topical application to animals or humans in cosmetic field, including solution, emulsion, spray, cream, ointment, salves, gel, etc., as described below. Exemplary agents are sufficiently viscous to be retained on those, those that are not easily evaporated on the treatment area, and / or by rinsing with water, optionally those that are easily removed under the assistance of soaps, detergents and / or shampoos.

[0111] The composition can be made into a variety of product types, including but not limited to solutions, suspensions, emulsions, pastes, gels, toners, rods, sprays, ointments, cleaning detergents and solid rods, shampoos and conditioners, pastes, foams, powders, mousses, shaving creams, wipes, strips, patches, electric patches, wound dressings and adhesive bandages, hydrogels, film-forming products, facial masks and body masks, facial cosmetics such as foundations, eyeliners and eye shadow lamps. These product types 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.

[0112] Cosmetically acceptable vehicle

[0113] The cosmetically acceptable vehicle may act as a diluent, dispersant or carrier for the skin benefiting ingredients in the composition to facilitate their distribution when the composition is applied to the skin.

[0114] The vehicle may be aqueous, anhydrous or an emulsion. Preferably, the composition is aqueous or an emulsion, especially a water-in-oil or oil-in-water emulsion, preferably an oil-in-water emulsion. When present, water may be in an amount of 5% to 99%, preferably from 20% to 70%, optimally between 40% and 70%.

[0115] In addition to water, relatively volatile solvents may also be used as carriers in the compositions of the present invention. Most preferred are monohydric C1-C3 alkanols. These include ethanol, methanol and isopropanol. The amount of monohydric alkanol may be 1 to 70 weight %, preferably 10 to 50 weight %, and optimally 15 to 40 weight %.

[0116] Emollient materials may also be used as cosmetically acceptable carriers. These may be in the form of silicone oils and synthetic esters. The amount of emollient may be anywhere from 0.1 to 50 wt %, preferably between 1 to 20 wt %.

[0117] Silicone oils can be divided into volatile and non-volatile categories. As used herein, the term "volatile" refers to those materials having 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. Straight-chain 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 that can be used as softening materials include polyalkylsiloxanes, polyalkylarylsiloxanes, and polyethersiloxane copolymers. Substantially non-volatile polyalkylsiloxanes that can be used in the present application include, for example, polydimethylsiloxanes having a viscosity of about 5 to about 25 million centistokes at 25°C. Preferred non-volatile softeners that can be used in the compositions of the present invention include polydimethylsiloxanes having a viscosity of about 10 to about 400 centistokes at 25°C.

[0118] Ester softeners include:

[0119] (1) Alkenyl or alkyl esters of fatty acids having 10 to 20 carbon atoms. Examples thereof include isoarachidyl neopentanoate, isononyl isononanoate, oleyl myristate, oleyl stearate, and oleyl oleate.

[0120] (2) Ether-esters, such as fatty acid esters of ethoxylated fatty alcohols.

[0121] (3) Polyol 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, glycerol mono- and di-fatty acid esters, polyglycerol polyfatty esters, ethoxylated glycerol 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 satisfactory polyol esters.

[0122] (4) Wax esters such as beeswax, spermaceti, myristyl myristate, stearyl stearate and eicosanyl behenate.

[0123] (5) Sterol esters, of which cholesterol fatty acid esters are examples.

[0124] Fatty acids having 10 to 30 carbon atoms may also be included as cosmetically acceptable carriers for the compositions of the present invention. Examples of this class 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.

[0125] Polyol-type wetting agents can also be used as cosmetically acceptable carriers in the compositions of the present invention. Wetting agents help increase the effectiveness of softeners, reduce dry skin, and improve skin feel. Typical polyols include glycerol, polyalkylene glycols, more preferably alkylene polyols and derivatives thereof, including propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, 1,2,6-hexanetriol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof. By weight of the composition, the amount of wetting agent can be, for example, anywhere from 0.5% to 30%, preferably between 1% and 15%.

[0126] Thickeners can also be used as part of the cosmetically acceptable carrier of the composition according to the present invention. Typical thickeners include cross-linked acrylates (e.g., Carbopol 982), hydrophobically modified acrylates (e.g., Carbopol 1382), cellulose derivatives, and natural gums. Useful cellulose derivatives include sodium carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose, and hydroxymethyl cellulose. Suitable natural gums for use in the present invention include guar gum, xanthan gum, sclerotium, carrageenan, pectin, and combinations of these gums. The amount of the thickener can be 0.0001 to 5% by weight, typically 0.001 to 1% by weight, and optimally 0.01 to 0.5% by weight.

[0127] Water, solvents, silicones, esters, fatty acids, humectants and / or thickeners may together constitute the cosmetically acceptable carrier in an amount of 1 to 99.9% by weight, preferably 80 to 99% by weight.

[0128] The oil or oily material may be present together with an emulsifier to provide a water-in-oil or oil-in-water emulsion, depending largely on the average hydrophilic-lipophilic balance (HLB) of the emulsifier used.

[0129] Surfactants may also be present in the cosmetic compositions of the present invention. For leave-on products, the total concentration of surfactants may be from 0.1 to 40% by weight of the composition, preferably from 1 to 20% by weight, and optimally from 1 to 5% by weight. For rinse-off products such as cleansers and soaps, the total concentration of surfactants may range from about 1 to about 90%. The surfactants may be selected from anionic, nonionic, cationic, and amphoteric actives. Particularly preferred nonionic surfactants are those containing: C 200 mol of ethylene oxide or propylene oxide condensed with 2 to 100 mol of ethylene oxide or propylene oxide per mol of hydrophobe. 10 -C 20 Fatty alcohol or acid hydrophobe; C2-C 10 Alkylphenols; mono- and di-fatty acid esters of ethylene glycol; fatty acid monoglycerides, sorbitan mono- and di-C8-C 20 Fatty acids, block copolymers (ethylene oxide / propylene oxide); polyoxyethylene sorbitan and combinations thereof. Alkyl polyglycosides and sugar fatty amides (eg methyl glucamide) are also suitable nonionic surfactants.

[0130] 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 isethionate, acyl glutamate, C8-C 20 Alkyl ether phosphates and combinations thereof.

[0131] The cosmetic compositions of the present invention optionally include a lathering surfactant. "Lathering surfactant" refers to a surfactant that produces foam or lather when combined with water and mechanically agitated. Preferably, the lathering surfactant should be mild, meaning that it must provide adequate cleansing or detergent benefits, but not overly dry the skin, and also meet the lathering criteria described above. The cosmetic compositions of the present invention may include a lathering surfactant in a concentration of about 0.01% to about 50%.

[0132] The composition can be formulated as a solution. The solution typically includes an aqueous or organic solvent, such as about 50% to about 99.99%, or about 90% to about 99% of a 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. An example of such a solvent is a mixture of ethanol / polyethylene glycol (80 / 20).

[0133] Such solutions can be formulated into emulsions. Emulsions typically contain from about 1% to about 20% (e.g., from about 5% to about 10%) of an emollient and from about 50% to about 90% (e.g., from about 60% to about 80%) of water.

[0134] Another type of product that can be prepared by solution is ointment. Ointment usually contains about 5% to about 50% (e.g., about 10% to about 20%) of emollient and about 45% to about 85% (e.g., about 50% to about 75%) of water. Another type of product that can be prepared by solution is ointment. Ointment can contain a simple matrix of animal, plant or synthetic oil or semisolid hydrocarbon. Ointment can contain about 2% to about 10% of emollient plus about 0.1% to about 2% of thickener. Examples of thickeners include but are not limited to those listed in the ICI Handbook (International Cosmetic Ingredient Dictionary and Handbook) 1693-1697 pages.

[0135] The compositions described herein can also be formulated as emulsions. If 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 listed in the ICI Handbook, pages 1673-1686.

[0136] Emulsions and ointments can be formulated as emulsions. Typically, such emulsions contain 0.5% to about 5% emulsifiers, while such ointments typically contain about 1% to about 20% (e.g., about 5% to about 10%) of an emollient; about 20% to about 80% (e.g., 30% to about 70%) of water; and about 1% to about 10% (e.g., about 2% to about 5%) of an emulsifier.

[0137] Single emulsion skin care preparations such as emulsions and creams of the oil-in-water type and the water-in-oil type are well known in the art and can be used in the compositions and methods described herein. Multiphase emulsion compositions such as the water-in-oil-in-water type or the oil-in-water-in-oil type can also be used in the compositions and methods described herein. Typically, such single-phase or multiphase emulsions contain water, an emollient, and an emulsifier as essential ingredients.

[0138] The compositions described herein can also be formulated into gels (e.g., aqueous gels, alcohol gels, alcohol / hydrogels, or oleogels using suitable gelling agents). Suitable gelling agents for hydrogels and / or alcohol gels include, but are not limited to, natural gums, acrylic acid polymers and acrylate polymers and copolymers, and cellulose derivatives (e.g., hydroxymethyl cellulose and hydroxypropyl cellulose). Gelling agents for oils (such as mineral oils) include, but are not limited to, hydrogenated butylene / ethylene / styrene copolymers and hydrogenated ethylene / propylene / styrene copolymers. Such gels are typically comprised of such gelling agents between about 0.1% by weight and 5% by weight.

[0139] One or more additional agents may be added to the topical formulation to enhance the percutaneous absorption of the active ingredient, including but not limited to dimethyl sulfoxide, dimethylacetamide, dimethylformamide, surfactants, azone (laurylamide Physical methods can also be used to enhance transdermal penetration, such as iontophoresis or sonophoresis.

[0140] The topical compositions provided herein comprise a cosmetically effective agent having a desired effect on the skin as described herein, and those ingredients necessary for use as a carrier, such as a lotion, cream, ointment, aqueous solution, emulsion or aerosol.

[0141] The carrier used in the compositions described herein can be in a variety of forms. These include emulsion carriers, including 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, emulsions, or aerosols. Depending on the water solubility / dispersibility of the component in the composition, a given component will be primarily distributed into either the aqueous phase or the oil / silicone phase.

[0142] The dermatological formulations provided herein may generally include derivatives of any compound or composition described herein and an optional polar solvent. Suitable solvents for use in the formulations described herein include any polar solvents capable of dissolving the derivatives. Suitable polar solvents may include: water; alcohols (such as ethanol, propanol, isopropanol, hexanol and benzyl alcohol); polyols (such as propylene glycol, polypropylene glycol, butylene glycol, hexylene glycol, maltitol, sorbitol and glycerol); and panthenol dissolved in glycerol, flavor oils and mixtures thereof. Mixtures of these solvents may also be used. Exemplary polar solvents may be polyols and water. Examples of solvents may include glycerol, panthenol in glycerol, glycols such as propylene glycol and butylene glycol, polyethylene glycol, water and mixtures thereof. Additional polar solvents used may be alcohols, glycerol, panthenol, propylene glycol, butylene glycol, hexylene glycol and mixtures thereof.

[0143] Emollients may also be added to the cosmetic / dermatological compositions described herein. The emollient component may include fats, oils, fatty alcohols, fatty acids, and esters, which aid in application and adhesion, impart shine, and provide occlusive moisturization. Suitable emollients for use may be 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, olein glyceryl, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, isopropyl linoleate, pentaerythrityl tetraisostearate, neopentyl glycol dicaprylate / dicaprate, hydrogenated coconut glycerides, isononyl isononanoate, isotridecanol 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 generally comprise from about 1% to about 90% of the cosmetic composition, preferably from about 10% to about 80%, more preferably from about 20% to about 70%, and most preferably from about 40% to about 60%.

[0144] As used in this application, "polar softener" refers to any softening emulsifier having at least one polar part and wherein the solubility of the cell-protective derivative compound in the polar softener (at 30°C) is greater than about 1.5%, preferably greater than about 2%, and more preferably greater than about 3%. Suitable polar softeners may 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 softeners may include PG3 diisostearate, polyglycerol-2-sesquiisostearate, polyglycerol-5-distearate, polyglycerol-10-distearate, polyglycerol-10-diisostearate, acetylated monoglycerides, glyceryl esters, glyceryl tricaprylate / caprate, glyceryl ricinoleate, glyceryl isostearate, glyceryl myristate, glyceryl linoleate, polyalkylene glycols such as PEG 600, monoglycerides, 2-glyceryl monolaurate, sorbitan esters, and mixtures thereof.

[0145] As used in this application, "non-polar softener" refers to any softening emulsifier that does not have or only has a minimum permanent moment. Suitable non-polar softeners may include, but are not limited to, esters and straight or branched hydrocarbons. Non-limiting examples of such softeners may 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 the compound in the polar or non-polar softener may be determined according to methods known in the art.

[0146] Suitable oils include esters, triglycerides, hydrocarbons and silicones. These can be a single material or a mixture of one or more materials. They can generally comprise from 0.1% to about 100% of the softener component, preferably from about 5% to about 90%, and most preferably from about 70% to about 90%.

[0147] Suitable oils for use in the present application may be acetylated glyceryl esters of alcohols and polyols, caprylic and capric esters (such as those of glycols and glycerol), ricinoleic acid esters of alcohols and polyols (such as cetyl ricinoleate), PG-3 diisostearate, polyglyceryl ethers, polyglyceryl esters, caprylic triglyceride, capric triglyceride, isostearic triglyceride, adipic triglyceride, phenyl trimethicone, lanolin oil, polybutene, isopropyl palmitate, isopropyl isostearate, cetyl ricinoleate, octyldodecanol, oleyl alcohol, hydrogenated vegetable oil, castor oil, modified lanolin, octyl palmitate, lanolin oil, maleated soybean oil, cetyl ricinoleate, tricaprylin, diisopropyl dimerate, synthetic lanolin derivatives, as well as branched alcohols, sucrose fatty acid esters, octyl hydroxystearate, and mixtures thereof.

[0148] Preferably, the oils used are selected so that a 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 differ by no more than about 1 to about 0.1, preferably about 0.8 to about 0.1.

[0149] Surfactants may also be added to the compositions described herein to impart beneficial cosmetic or application properties. Suitable surfactants may be those that form emulsions and / or association structures. Surfactant emulsifiers may be present in an amount of 0% to about 20%, preferably 0% to about 15%, and most preferably about 1% to about 10% of the formulation.

[0150] Examples of surfactants that can be used in the composition described herein include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosinates such as sodium N-lauroyl sarcosinate and sodium N-myristoyl sarcosinate, sodium dodecylbenzene sulfonate, sodium hydrogenated coconut fatty acid monoglyceride sulfate, sodium lauryl sulfoacetate, and N-acyl glutamates such as N-palmitoyl glutamate, sodium N-methylacyl taurine, sodium N-methylacyl alanine, sodium α-olefin sulfonate, and sodium dioctyl sulfosuccinate; N-alkylaminoglycerols such as N-lauryl-diamino-ethylglycerol; Oil and N-myristyl diaminoethyl glycerol, N-alkyl-N-carboxymethyl ammonium betaine and 2-alkyl-1-hydroxyethyl imidazoline betaine sodium; polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyoxyethylene lanolin alcohol, polyoxyethylene glycerol monofatty acid ester, polyoxyethylene sorbitol aliphatic acid ester, polyoxyethylene aliphatic acid ester, higher aliphatic acid glyceride, sorbitan aliphatic acid ester, Pluronic surfactant, and polyoxyethylene sorbitan aliphatic acid ester such as polyoxyethylene sorbitan monooleate and polyoxyethylene sorbitan monolaurate. Emulsifier surfactants known to those skilled in the art can be used in the composition described in the present application.

[0151] Also useful in the present application may be a surfactant that forms an association structure, preferably a lamellar or hexagonal liquid crystal, at ambient temperature when mixed with a polar solvent. In preparing a sample combination of a surfactant and a polar solvent to demonstrate the ability to form an association structure, the surfactant needs to be sufficiently soluble in the polar solvent so that an association structure can be formed at ambient temperature.

[0152] Any surfactant that forms an association structure at ambient temperature and is suitable for use in cosmetics may be suitable for use in this application. Surfactants suitable for use in cosmetics should have no or minimal dermatological or toxicological problems. Anionic surfactants, nonionic surfactants, cationic surfactants, amphoteric surfactants, and mixtures thereof may be suitably used.

[0153] The surfactant may be used at a level of from about 4% to about 97%, preferably from about 5% to about 95%, more preferably from about 20% to about 90%, most preferably from about 30% to about 70% of the association structure.

[0154] The cosmetic compositions described herein may include one or more materials, referred to herein individually or collectively as "curing agents", which are effective to cure the specific liquid base materials used in the cosmetic composition. (As used herein, the term "curing" refers to the physical and / or chemical change of the liquid base material to form a solid or semi-solid under ambient conditions, i.e., to form a final composition having a stable physical structure and which can be deposited on the skin under normal conditions of use). As will be appreciated by those skilled in the art, the selection of a specific curing agent for a cosmetic composition may depend on the specific type of composition desired, i.e., gel- or wax-based, the desired rheology, the liquid base material used, and the other materials to be used in the composition. The curing agent may preferably be present in a concentration of 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%.

[0155] The wax beauty stick variant provided in the present application preferably may contain about 5% to about 50% (by weight) of a waxy solidifying agent. As used in the present application, the term "waxy solidifying agent" refers to a solidifying material having waxy properties. Such a waxy material may also be used as a softener. The waxy material that can be used in the present application is a high melting point wax, i.e., a wax having a melting point of about 65°C to about 125°C, such as beeswax, spermaceti, carnauba wax, bayberry, candelilla wax, montan wax, ozokerite, ceresin, paraffin, synthetic waxes such as Fisher-Tropsc wax, microcrystalline wax, and mixtures thereof. Among those waxes, ceresin, ozokerite, white beeswax, synthetic wax, and mixtures thereof are useful in the present application. Low melting point waxes having a melting point of about 37°C to about 75°C may preferably be used in the wax stick variant described in the present application. Variations of wax sticks containing volatile silicone oils as the liquid base material preferably contain from about 10% to about 35%, more preferably from about 10% to about 20% (by weight) of low melting wax. Such materials include fatty acids, fatty alcohols, fatty acid esters and fatty acid amides having a fatty chain of from about 8 to about 30 carbon atoms, and mixtures thereof. Waxy materials include cetyl alcohol, palmitic acid, stearyl alcohol, behenamide, 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 used in most cases. Additional fatty acids, fatty alcohols and other waxy materials are also well known in the art.

[0156] In addition, these compositions may include other cosmetic agents, carriers, adjuvants, etc. Some specific additional agents may include sunscreens; retinoids; antioxidants; hydroxy acids; acceptable non-toxic metal salts of fatty acids, naturally occurring amino acids or hydroxyalkyl acids; plant extracts, salicylic acid, benzoyl peroxide, antibiotics, anti-androgens, anti-inflammatory agents, antioxidants, ascorbic acid, vitamin B, tocopherols or tocotrienols, corticosteroids, wetting agents, surfactants, keratolytic agents, complexing agents, colorants, fragrances, and mixtures thereof.

[0157] Synthesis method

[0158] The resorcinol compounds described in the present application can be synthesized by an appropriate combination of generally well-known synthesis methods. Based on the teachings described in the present application, the techniques that can be used to synthesize the compounds of the present application are obvious and easily accessible to those skilled in the relevant art.

[0159] 4-Alkylresorcinol is commercially available from Sigma-Aldrich, St. Louis, MO, USA. DETAILED DESCRIPTION

[0160] Example

[0161] Example 1

[0162] Evaluation of Degradation and Stabilization Signs of 4-Alkylresorcinol

[0163] Color determination

[0164] Samples for color evaluation were prepared by dissolving 4-hexylresorcinol (200 mg) or 4-ethylresorcinol (200 mg) in deionized water:butylene glycol (4:1; 20 ml) to produce a clear, colorless, homogeneous solution. A portion (5 ml) of each solution was added to a 20 ml scintillation vial containing nicotinamide (B3) (50 mg), AceMet (acetylmethionine) (50 mg), or B3 (50 mg) + AceMet (50 mg) and monitored at room temperature (~20-22°C). After 2 weeks, the color of each solution was visually evaluated and the L*a*b* measurements were experimentally 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 the color content and intensity from green (a*<0) to neutral gray (a*=0) to red (a*>0). The b* parameter also measures the color content and intensity from blue (b*<0) to neutral gray (b*=0) to yellow (b*>0).

[0165] Quantification of 4-Alkylresorcinol

[0166] After 2 weeks at room temperature (-20-22°C), the amount of 4-alkylresorcinol present in each sample for color measurement was quantified by high performance liquid chromatography (HPLC). A sample aliquot (100uL) from each color measurement solution was diluted with deionized water: acetonitrile (1:1, 900uL) to generate a test sample (1ml). An aliquot (10uL) of each test sample was injected into a Waters 2695 separation module, chromatographed and separated on a Restek Pinnacle DB C18 (5um, 4.6X 150mm) column running at 30°C and 4-alkylresorcinol was monitored using a Waters 2996 photodiode array detector set at 281nm. The mobile phase consisted of water (A) and acetonitrile (B), and a gradient from 95:5 (A:B) to 5:95 (A:B) was used to achieve optimal separation in 20 minutes, followed by isocratic elution at 5:95 (A:B) for 3 minutes at a flow rate of 1 ml / min. Chromatographic data were processed using Empower 2 software (Waters Corporation, Milford, MA). Standard control samples of 1X, 5X higher concentration, and 5X lower concentration of 4-alkylresorcinol were freshly prepared and analyzed immediately; standard curves were generated and linearity confirmed over the range of the tested samples.

[0167] All samples were analyzed in duplicate and the average values ​​were reported. The amount of 4-alkylresorcinol present for each test sample after 2 weeks was determined by measuring the chromatographic peak area under the 281 nm curve for 4-alkylresorcinol and expressed as a percentage relative to the corresponding chromatographic peak area under the 281 nm curve for a freshly prepared control sample.

[0168] 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 niacinamide "B3". Freshly prepared HR solutions were colorless and no decomposition of HR was observed in HPLC analysis. After 2 weeks, the color of the HR solution changed to pink as evidenced 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 significantly accelerated the decomposition of HR by 55% and produced a more intense color, as seen by a further significant increase in a*, b* and a decrease in L*. In contrast and unexpectedly, the addition of AceMet to the HR solution significantly prevented color formation and HR decomposition in the presence or absence of B3, as evidenced by the corresponding L*a*b* values ​​and HR content very close to control levels. Similarly, AceMet significantly prevented color formation in ER solutions in the presence or absence of B3 and provided protection against ER decomposition, albeit to a slightly lesser extent than HR. These results clearly demonstrate the significant benefits of AceMet on the color and chemical stability of 4-alkylresorcinol in the presence or absence of other cosmetic ingredients (such as B3) that can further accelerate the formation and decomposition of this color.

[0169] The table below shows the effect of AceMet on the color and stability of 4-alkylresorcinols (HR and ER) in the presence and absence of B3 after 2 weeks at room temperature (-20-22°C):

[0170] Table 1

[0171]

[0172]

[0173] a Control = deionized water:butylene glycol (4:1).

[0174] b Visual appearance of the solution after 2 weeks.

[0175] c Determined by HPLC analysis.

[0176] Example 2. ER and AceMet

[0177] Topical cosmetic compositions within the scope of the present invention are prepared.

[0178] Prepare the base formulation shown in the table below by heating the Phase A ingredients to 70 to 85°C with stirring. Heat the Phase B ingredients to 70 to 85°C with stirring in a separate container. Then, add Phase A to Phase B while keeping both phases at 70 to 85°C. Stir the mixture at 70 to 85°C for at least 15 minutes and then cool. Add the Phase C ingredients at 50°C, followed by the Phase D ingredients at 40°C.

[0179] Table 2. Basic formulation

[0180]

[0181]

[0182] Example 3

[0183] Additional cosmetic compositions falling within the scope of the present invention were prepared as shown in the following table.

[0184] Table 3

[0185]

[0186]

[0187] The composition was prepared as follows:

[0188] 1. Heat phase A to 80°C while mixing.

[0189] 2. Heat Phase B to 75°C in a separate container while mixing.

[0190] 3. Add B to A and mix for 15 minutes with heat maintained at 70-80°C; then turn off heat and continue mixing for another 15 minutes.

[0191] 4. Add phase C at 50°C and mix for 10 minutes.

[0192] 5. Add phase D at 40°C and mix for 10 minutes.

[0193] Example 4-11

[0194] A group of additional compositions within the scope of the present invention were prepared by the method of Example 2 and are listed in the table below.

[0195] Table 4. HR and AceMet

[0196]

[0197] Example 12

[0198] The formulations in the following table were prepared according to the method described in Example 1 above.

[0199] Table 5: Formulations for skin care lotions (skin emulsions)

[0200]

[0201]

Claims

1. A topical cosmetic composition comprising: a. 0.0001 to 5% N-acetylmethionine; b. 0.00001 to 10% of one or more 4-substituted resorcinol derivatives of the general formula I: wherein each R1 and R2 are independently selected from hydrogen atom, -CO-R, -COO-R and CONHR; wherein R represents C1–C 18 hydrocarbon; and c. Cosmetically acceptable vehicles; Wherein R3 is hexyl.

2. The topical cosmetic composition of claim 1, wherein R1 and R2 are both H.

3. The topical cosmetic composition of claim 1 or 2, further comprising a skin benefit agent selected from the group consisting of alpha-hydroxy acids and esters thereof, beta-hydroxy acids and esters thereof, polyhydroxy acids and esters thereof, kojic acid and esters thereof, ferulic acid and ferulic acid esters, vanillic acid and esters thereof, diacids and esters thereof, retinol, retinal, retinyl esters, hydroquinone, tert-butylhydroquinone, 1-methylnicotinamide chloride, and mixtures thereof.

4. The topical cosmetic composition according to claim 1 or 2, wherein the N-acetylmethionine is present in an amount of 0.0001 wt % to 5 wt % of the cosmetic composition; and The weight ratio of the N-acetylmethionine to the 4-substituted resorcinol derivative is 10,000:1 to 1:100,000.

5. A method of stabilizing 4-ethylresorcinol or 4-hexylresorcinol in a composition comprising a cosmetically acceptable vehicle by adding to the composition an amount of N-acetylmethionine sufficient to stabilize the 4-ethylresorcinol or 4-hexylresorcinol.

6. Use of N-acetylmethionine for stabilizing 4-ethylresorcinol or 4-hexylresorcinol in a composition comprising a cosmetically acceptable vehicle.

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