RU2818915C2 - Stabilization of resorcinol compounds in cosmetic compositions - Google Patents

Abstract

FIELD: cosmetic industry.

SUBSTANCE: group of inventions relates to cosmetic compositions for local application. Cosmetic composition contains from 0.00001 to 10 wt.% N-acetylmethionine; from 0.00001 to 10 wt.% of one or more 4-substituted resorcinol derivatives of general formula I

(I),

where each R₁ and R₂ is independently selected from the group consisting of a hydrogen atom, -CO-R, -COO-R and CONHR; where R is C₁-C₁₈ hydrocarbon and R₃ is ethyl; and a cosmetically acceptable carrier. Also disclosed stabilized cosmetic composition, method of stabilizing 4-ethylresorcinol or 4-hexylresorcinol in a composition, use of N-acetylmethionine and 4-ethylresorcinol when preparing a cosmetic composition for local application.

EFFECT: group of inventions provides improved storage stability and oxidation resistance.

6 cl, 5 tbl, 12 ex

Description

Field of technology

Provided herein are cosmetic compositions for topical application containing 4-position (4-substituted) resorcinol derivatives stabilized with acetylmethionine.

State of the art

The beauty that the observer sees is influenced by many physiological and genetic factors. The basis of a natural appearance, perceived as beauty, is the skin, including hair. Ideal skin should be smooth and even, without visible surface damage, and appear transparent with an even color distribution. Skin and hair problems in aging people can be the result of a wide variety of external or internal factors, such as harmful UV radiation from the sun, environmental exposure, stress, fatigue, illness, or a combination of these.

To achieve a positive cosmetic effect on the skin and hair, resorcinol derivatives (1,3-benzenediol) were used. Derivatives of 4-substituted resorcinol and their preparation were used for skin lightening and other cosmetic purposes; see, for example, US Patent No. 4,959,393, US Patent No. 6,132,740, US Patent Application Publication No. 2008/0131382, and Japanese Patent Application Publication Nos. JP 2001-01 0925 and JP 2000-327557. Resorcinol-type skin lightening agents that can be synthesized using coumarin as a starting material are described in US Patent Application Publication No. 2004/0042983. However, some of these compounds may be difficult to synthesize because they are not stable in a cosmetically acceptable carrier.

Oxidative instability is an undesirable characteristic 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 will inhibit the oxidation of 4-substituted resorcinols.

It would be desirable to provide cosmetic compositions for topical application containing resorcinol derivatives stabilized against factors such as discoloration, oxidation, and general storage stability. The compositions described herein containing 4-alkylresorcinols stabilized with N-acetylmethionine (AceMet) meet this need.

The essence of the invention

a. from about 0.00001 to about 10% N-acetylmethionine,

b. from about 0.00001 to about 10% 4-substituted resorcinol derivative,

And

c. filler or carrier.

The 4-substituted resorcinol derivative is stabilized against degradation/discoloration/oxidation by including N-acetylmethionine in the composition. The present compositions contain cosmetically effective amounts of resorcinol compounds and N-acetylmethionine in an amount sufficient to stabilize the resorcinol compounds against chemical degradation, as evidenced by discoloration.

The resorcinol derivatives provided herein, as defined below, are useful for treating or preventing one or more cosmetic conditions as desired by a subject in need thereof, for example, preventing, alleviating, reducing or treating the signs or appearance of unwanted skin pigmentation caused by one or more pathological conditions.

Derivatives of 4-substituted resorcinol have the general formula I:

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;

R ₃ is a C ₁ -C ₁₈ hydrocarbon or has the general formula (II):

where X represents hydrogen; OR ¹ where R ¹ represents hydrogen, (C ₁ -C ₆ )alkyl or aryl-(C ₁ -C ₆ )alkyl; OCOR ² where R ² represents (C ₁ -C ₆ )alkyl, aryl-(C ₁ -C ₆ )alkyl or phenyl; (C ₁ -C ₆ )alkyl; aryl(C ₁ -C ₆ )alkyl; or NHR ¹ , where R ¹ is defined above;

n ranges from 0 to 3; And

the dotted line indicates an optional double bond;

and preferably include linear 4-alkylresorcinols, branched 4-alkylresorcinols, 4-cycloalkylresorcinols, and mixtures thereof.

More preferred resorcinol derivatives include 4-ethylresorcinol, 4-isopropylresorcinol, 4-hexylresorcinol and 4-cyclohexylresorcinol, as well as O-acylated variants thereof.

According to another embodiment, a stabilized cosmetic composition is provided containing:

A. 4-substituted resorcinol derivative stabilized with N-acetylmethionine;

b. optionally an agent having a beneficial effect on the skin; And

c. a cosmetically acceptable carrier;

wherein said N-acetylmethionine is present in an amount of from about 0.0001 to about 5 wt.% relative to the weight of said cosmetic composition; And

wherein the weight ratio of said N-acetylmethionine to said 4-substituted resorcinol derivative is from about 10,000:1 to about 1:100,000.

The compositions of the present invention are aesthetically pleasing and the resorcinol derivatives contained therein have improved storage stability/color/oxidation resistance.

Also proposed is a method of stabilizing (against oxidation, discoloration, storage, etc.) 4-hexylresorcinol in a composition containing a cosmetically acceptable carrier by adding N-acetylmethionine to said composition in an amount sufficient to stabilize said 4-hexylresorcinol.

In addition, the use of N-acetylmethionine and any derivatives of 4-substituted resorcinol in the preparation of a cosmetic composition for topical application to the skin of a subject in need is described.

In another embodiment, provided herein is a method of regulating a skin condition by topically applying to the skin of a subject in need thereof an effective amount of compositions of the present invention containing 4-substituted resorcinol derivatives and N-acetylmethionine.

Further provided herein is a product containing instructions directing the user how to use a composition, including a skin care composition, containing one or more 4-substituted resorcinol derivatives, which compositions also contain N-acetylmethionine as a stabilizer. The composition may contain pharmaceutically and/or dermatologically acceptable carriers and excipients.

The compositions of the present invention are aesthetically pleasing and have improved storage stability/oxidation resistance.

Detailed Description of the Invention

Definitions

As used herein, a “subject” is a mammal, specifically a human. It will be understood that administration to a subject may also include application "to" the subject; that is, administration to a subject may include internal use, external use, or both, according to the context of use.

As used herein, “applying to the skin where such treatment is desired” means bringing into contact (for example, by hand or by application of an applicator such as, but not limited to, a wipe, tube, bandage, spray, or patch) to an area of skin, in need of such treatment, or an area of skin located near the area of skin in need of such treatment.

As used herein, “composition” means a composition suitable for topical administration to the skin.

As used herein, the term “cosmetic composition” is intended to describe compositions for topical application to the skin of a subject, including leave-on products and rinse-off products.

As used herein, the term “skin” includes skin on the face, neck, chest, back, arms, armpits, hands, legs, and scalp of a subject.

Except in examples or where expressly indicated otherwise, all numbers in this specification indicating amounts of material or reaction conditions, physical properties of materials and/or applications are to be understood as modified by the word “about.” All amounts are by weight relative to the weight of the composition unless otherwise indicated.

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 stages or options listed do not have to be exhaustive.

For all compositions described herein and all methods in which a composition described herein is used, said compositions and methods may either include recited components or steps or may “consist essentially of” recited components or steps. When a composition is described as "consisting essentially of" listed components, said composition contains the listed components and may contain other components that do not substantially affect the skin or skin condition being treated, but does not contain any other components that significantly affect the skin or pathological skin condition being treated, with the exception of those components that have been specifically listed; or, if the composition does contain additional components other than those listed that substantially affect the skin or skin condition being treated, said composition does not contain such additional components in a concentration or amount sufficient to significantly affect the skin or skin condition being treated. the skin condition being treated. When a method is described as “consisting essentially of” listed steps, the method includes the listed steps and may include other steps that do not significantly affect the skin or skin condition being treated, but the method does not include any other steps that significantly affect the skin or skin condition being treated beyond those stages specifically listed.

As used herein, the term "cosmetically acceptable" or "dermatologically acceptable" means that the compositions or components thereof so described are suitable for use in contact with skin, particularly human skin, without causing undue toxicity, incompatibility, instability, irritation or allergic reaction.

As used herein, the term "cosmetically acceptable carrier", "cosmetically acceptable excipient", "dermatologically acceptable carrier" or "dermatologically acceptable excipient" includes all solvents, dispersants, coatings, antibacterial and antifungal agents, isotonic agents and absorption retardants, and the like, which are cosmetically acceptable or dermatologically acceptable. It is contemplated that they may be used in cosmetic compositions unless any conventional vehicle or agent is incompatible with the active ingredient. Additional active ingredients may also be included in the compositions. Cosmetically acceptable carriers are suitable for topical application to the skin, have good aesthetic properties, are compatible with the active substances described herein and any other components, and pose minimal or no safety or toxicity concerns. A safe and effective amount of carrier is from about 50% to about 99.99%, or from about 50% to about 99%, preferably from about 80% to about 99.9%, or from about 75% to about 99%, more preferably from about 90% to about 98% and most preferably from about 90% to about 95% or from about 85% to about 95% based on the composition. Percentages are preferably expressed as percent mass concentration.

As used herein, the terms “skin condition”, “dermatological disease” and “dermatological condition” are used interchangeably.

As used herein, the term “sunscreen” may include, but is not limited to, organic or inorganic sunscreens such as methoxycinnamate, oxybenzone, avobenzone, and the like; sunscreens such as titanium oxide and zinc oxide; and skin protection products; or mixtures thereof.

As used herein, the term “topical application” means applying or distributing the compositions described herein over the surface of the skin.

As used herein, “alkyl” is meant to include a saturated straight or branched hydrocarbon chain of the specified number of carbon atoms. In one embodiment, alkyl groups can contain from 1 to 12 carbon atoms. "Alkylene" is meant to include a divalent saturated straight or branched hydrocarbon chain with a given number of carbon atoms. In one embodiment, alkylene groups can contain from 1 to 12 carbon atoms.

As used herein, “cycloalkyl” is meant to include a saturated cyclic hydrocarbon chain with a specified number of carbon atoms. In one embodiment, cycloalkyl groups can contain from 3 to 12 carbon atoms.

As used herein, “alkenyl” is meant to include a straight or branched hydrocarbon chain containing at least one carbon-carbon double bond. In one embodiment, alkenyl groups can contain from 2 to 12 carbon atoms.

As used herein, "aryl" is meant to include an aromatic hydrocarbon, such as, for example, a substituted or unsubstituted phenyl or naphthyl group.

Although the compounds described herein may occur and be used as a neutral (non-salt) compound, the present disclosure is intended to include all salts of the compounds described herein, as well as methods of using such salts of the compounds disclosed herein. In one embodiment, salts of these compounds include pharmaceutically acceptable salts and/or dermatologically acceptable salts. Cosmetically acceptable salts are those salts that can be applied to the skin of humans and/or animals and which, after application, retain at least some of the biological activity of the free compound (neutral compound or non-salt compound). The desired salt of the base compound can be prepared using 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 acid, mandelic acid, sulfonic acids and salicylic acid. It is also possible to obtain salts of basic compounds with amino acids, such as aspartates and glutamates. Examples of inorganic salts of acidic compounds include, but are not limited to, alkali metal and alkaline earth metal salts such as sodium salts, potassium salts, magnesium salts 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. It is also possible to obtain salts of acidic compounds with amino acids, such as lysine salts.

COMPOSITIONS

Derivatives of 4-substituted resorcinol

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

The compositions of the present invention contain an effective amount of a resorcinol derivative of the following formula (I):

Each R ₁ and R ₂ independently represents a hydrogen atom, -CO-R (acyl group), -COO-R, CONHR; The last three groups can be represented by the following formula A, respectively:

where R represents a saturated or unsaturated, linear, branched or cyclic C ₁ -C ₁₈ hydrocarbon. In a preferred embodiment, each or both R ₁ and/or R ₂ are hydrogen. In a more preferred embodiment, both R ₁ and R ₂ are hydrogen.

R ₃ represents:

(1) a saturated or unsaturated, linear, branched or cyclic C ₁ -C ₁₈ hydrocarbon, preferably a C ₂ -C ₁₂ hydrocarbon;

or

(2) a group of general formula (II)

Where X represents hydrogen; OR ¹ where R ¹ represents hydrogen, (C ₁ -C ₆ )alkyl or aryl-(C ₁ -C ₆ )alkyl; OCOR ² where R ² represents (C ₁ -C ₆ )alkyl, aryl-(C ₁ -C ₆ )alkyl or phenyl; (C ₁ -C ₆ )alkyl; aryl(C ₁ -C ₆ )alkyl; or NHR ¹ , where R ¹ is defined above;

where n is from 0 to 3; and where the dotted line indicates an optional double bond.

For example, if n is 0, the group of general formula II is a 5-membered ring; if n is 1, the indicated group is a 6-membered ring; if n is 2, 7-membered ring; and if n is 3, an 8-membered ring.

4-Substituted resorcinols: linear or branched

In the above formula (1), the group represented by R ₃ and preferably containing from 2 to 12 carbon atoms, the arrangement of which is linear, may include an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, an undecyl group and a dodecyl group. Such linear alkyl groups may contain a methyl or ethyl group as a substituent in place of one or more hydrogen atoms. Specific examples of the substituted alkyl group include isopropyl group, isobutyl group, isoamyl group, 2-methylhexyl group and the like. Preferred alkyl groups are those in which R ₃ represents an ethyl, propyl, isopropyl, butyl, pentyl, hexyl, heptyl or octyl group. The most preferred alkylresorcinols are alkylresorcinols in which R ₃ represents an ethyl, isopropyl or hexyl group.

4-Cycloalkylresorcinol

In the case of resorcinol derivatives of formula (I), where R ₃ represents the structure of the general formula (II) shown above, the resorcinol derivatives are referred to herein as 4-cycloalkylresorcinols and are represented by the general formula (III):

In general formula (III) (and also in formula (II) above):

X represents hydrogen; OR ¹ where R ¹ represents hydrogen, (C ₁ -C ₆ )alkyl or aryl-(C ₁ -C ₆ )alkyl; OCOR ² where R ² represents (C ₁ -C ₆ )alkyl, aryl-(C ₁ -C ₆ )alkyl or phenyl; (C ₁ -C ₆ )alkyl; aryl(C ₁ -C ₆ )alkyl; or NHR ¹ , where R ¹ is defined above;

n ranges from 0 to 3; and the dotted line indicates an optional double bond at this position.

Examples of more specific embodiments of 4-cycloalkylresorcinols include:

(a) compounds of formula (III) in which a single bond connects two carbon atoms on the dotted line;

(b) compounds of formula (III) in which n is equal to one;

(c) compounds of formula (III) in which X represents hydrogen;

(d) compounds of formula (III) in which X represents hydrogen, methyl or ethyl;

(e) compounds of formula (III) in which n is zero;

(f) compounds of formula (III) in which n is two; And

(g) compounds of formula (III) in which X represents benzyloxy.

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

The amount of the resorcinol derivative is from about 0.00001% to about 10%, preferably from about 0.001 to about 7%, most preferably from about 0.01 to about 5% by weight, based on the total amount of the cosmetic composition.

N-acetyl-amino acids

The authors of the present application have discovered that N-acetyl-amino acids suppress the oxidation of 4-substituted resorcinol derivatives. According to the present invention, N-acetylamino acids are preferably used to stabilize 4-substituted resorcinols included in cosmetic compositions.

Acetylmethionine is an 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:

Acetylmethionine (CAS No. 1115-47-5 for acetyl-DL-methionine and CAS No. 65-82-7 for N-acetyl-L-methionine (“AceMet”)) has been used for cosmetic use. For purposes of the present invention, N-acetyl-L-methionine (“AceMet”) is preferred due to its improved solubility profile (water solubility, logP and logD) compared to L-methionine.

AceMet is a nutritionally and metabolically equivalent form of the essential amino acid L-methionine (L-Met), the latter used as an intermediate for the biosynthesis of S-adenosylmethionine (SAMe), an essential nutrient for maintaining optimal cellular energy balance - and also many important biomolecules, including cysteine, carnitine, taurine, lecithin, phosphatidylcholine. AceMet has also been shown to have detoxifying properties (e.g. as an antidote for paracetamol overdose, in the detoxification of benzene derivatives) and is considered stable in formulation (WO 0040217, WO 05055947). N-acetylamino acids (eg AceMet) have been used as part of a combination of several active substances for topical cosmetic use for the treatment of skin diseases (related to aging, hair, nails, etc.) (WO 00/40717, Tristrata Inc.).

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

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 resorcinols. A particular advantage of the compositions of the present invention is that 4-substituted resorcinols can be stabilized against oxidation by AceMet.

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

The amount of AceMet in the cosmetic composition is preferably from about 0.00001 to about 10%, more preferably from about 0.0001 to about 5% by weight, most preferably from about 0.0001 to about 2%.

OPTIONAL COMPONENTS

Any of the compounds described herein can 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 Vaseline® (a registered trademark of Conopco Corp., Englewood Cliffs, NJ), cetyl alcohol, isostearyl alcohol, cetyl-2-ethylhexanoate, 2-octyldodecyl alcohol, glycerin, glycerin triisostearate, nut oils and lanolin, as well as waxes, silicones, surfactants, thickeners, neutralizing agents, antiseptics, germicides, antioxidants, powders ingredients, pigments, fragrances, UV absorbers, pharmaceuticals, metal sealants and pH modifiers.

AGENTS HAVING A FAVORABLE EFFECT ON THE SKIN

The cosmetic compositions of the present invention can be used in personal care and wash products such as, for example, lotions, soaps, deodorants, etc. The N-acetylmethionine compounds and stabilizing agents that constitute the compositions of the present invention may have other benefits functions when incorporated into personal care compositions.

Preferred personal care compositions are compositions suitable for application to human skin which optionally, but preferably, contain a skin benefiting agent. Suitable skin benefiting agents include anti-aging agents, anti-wrinkle agents, skin whitening agents, anti-acne agents and sebaceous reducers. Examples of these agents include alpha hydroxy acids and their esters, beta hydroxy acids and their esters, polyhydroxy acids and their esters, kojic acid and its esters, ferulic acid and ferulate derivatives, vanillic acid and its esters, dicarboxylic acids (such as sebacic and azoleic acids) and their esters, retinol, retinal, retinyl esters, hydroquinone, tert-butylhydroquinone, mulberry extract, licorice root extract, 1-methylnicotinamide chloride and resorcinol derivatives other than the 4-substituted resorcinol derivatives described higher.

In addition, the active compounds described herein can be used in combination with skin exfoliants (including glycolic acid or trichloroacetic acid based facial exfoliants) or skin exfoliants (including retinoids such as retinoic acid). acid or retinol) to lighten skin color and prevent repigmentation. The appropriate dosage regimen, the amount of each dose administered, and the specific intervals between doses of the active compound will depend on the particular active compound used, the condition of the patient or subject being treated, and the nature and severity of the disorder or disease being treated. The active compound is preferably administered in a certain amount and at a certain interval that promotes the desired treatment or causes an improvement in the disorder or condition being treated.

The active compound described herein can also be used in combination with sunscreens (UVA or UVB blockers, absorbents, light scattering agents) to prevent or protect against skin damage caused by the sun or ultraviolet radiation.

In some embodiments, the composition further comprises ascorbic acid, its derivatives and ascorbic acid-based products (such as magnesium ascorbate) or other products with an antioxidant mechanism (such as resveratrol, tocopherols, tocotrienols and derivatives).

In some embodiments, the composition further comprises soy extract, which is a mixture of compounds isolated from soybeans. The soy extract may contain only a portion of the soy (eg, a soy extract such as reduced lipid soy powder or filtered soy milk) or may contain all of the soy (eg, ground soy powder). Soy extract can be in the form of a liquid (such as soy milk) or a solid (such as soy powder or soy milk powder).

The appropriate dosage regimen, the amount of each dose administered, and the specific intervals between doses of each topical active agent providing skin benefit will depend on the particular combination of active agents used, the condition of the patient requiring it, and the nature and severity of the local cosmetic condition. subject.

In the cosmetic compositions provided herein, the concentration of active compound is typically from 0.01% to 10%, or from about 0.01% to about 10%, such as 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% relative to the total mass of the composition.

The compositions described herein can be applied directly to the skin. Alternatively, they can be delivered using various transdermal delivery systems, such as transdermal patches known in the art. For example, for topical administration, the active ingredient may be formulated in a solution, gel, lotion, ointment, cream, suspension, paste, liniment, powder, tincture, aerosol, patch, or the like. in a cosmetically acceptable form using methods known in the art. The composition may be in any of various forms commonly used in the cosmetic arts for topical use in animals or humans, including solutions, lotions, sprays, creams, ointments, balms, gels, and the like, as described below. Typical agents are substances that are viscous enough to remain on the treated area, substances that do not evaporate easily, and/or substances that can be easily removed by washing with water, optionally with soap, detergents and/or shampoos.

The compositions can be formulated into a wide variety of product types, including, but not limited to, solutions, suspensions, lotions, creams, gels, toners, pomades, sprays, ointments, liquid cleansers and solid bars of soap, shampoos and hair conditioners, pastes, foams, powders, mousses, shaving creams, wipes, strips, patches, electric patches, wound dressings and adhesive bandages, hydrogels, film-forming products, face and skin masks, makeup products, such as foundations, eyeliner pencils and eye shadows, etc. These types of products may contain several types of cosmetically acceptable carriers, including, but not limited to, solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, solids and liposomes.

COSMETICALLY ACCEPTABLE CARRIER

In the present composition, a cosmetically acceptable carrier may act as a diluent, dispersant or excipient for the skin benefit ingredients to facilitate their distribution when the composition is applied to the skin.

The carrier may be aqueous, anhydrous, or an emulsion. The compositions according to the invention are preferably aqueous or an emulsion, in particular a water-in-oil or oil-in-water emulsion, preferably an oil-in-water emulsion. Water, if present, will be present in amounts that may range from 5 to 99%, preferably from 20 to 70%, optimally from 40 to 70% by weight.

In addition to water, relatively volatile solvents can also serve as carriers in the compositions of the present invention. The most preferred are monohydric C ₁ -C ₃ alkanols. These include ethyl alcohol, methyl alcohol and isopropyl alcohol. The amount of monohydric alkanol can be from 1 to 70%, preferably from 10 to 50%, optimally from 15 to 40% by weight.

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

Silicone oils can be divided into volatile and non-volatile. As used herein, the term “volatile” refers to those substances that have a measurable vapor pressure at ambient temperature. Volatile silicone oils are preferably selected from cyclic or linear polydimethylsiloxanes containing from 3 to 9, preferably from 4 to 5 silicon atoms. The viscosity of linear volatile silicone substances is typically less than about 5 centistokes at 25°C, while cyclic substances typically have a viscosity of less than about 10 centistokes. Fixed silicone oils useful as emollients include polyalkylsiloxanes, polyalkylarylsiloxanes, and polyester-siloxane copolymers. Substantially non-volatile polyalkylsiloxanes useful in the present invention include, for example, polydimethylsiloxanes with a viscosity of from about 5 to about 25 million centistokes at 25°C. Preferred non-volatile emollients useful in the present compositions include polydimethylsiloxanes having a viscosity of from about 10 to about 400 centistokes at 25°C.

Ester-based emollients include:

(1) Alkenyl or alkyl esters of fatty acids containing from 10 to 20 carbon atoms. Examples of such substances include isoarachidyl neopentanoate, isononyl isonononoate, oleyl myristate, oleyl stearate and oleyl oleate.

(2) Esters of alkoxy acids, such as esters of fatty acids and ethoxylated fatty alcohols;

(3) Esters of polyhydric alcohols. Mono- and diesters of ethylene glycol and fatty acids, mono- and diesters of diethylene glycol and fatty acids, mono- and diesters of polyethylene glycol (200-6000) and fatty acids, mono- and diesters of propylene glycol and fatty acids, polypropylene glycol monooleate 2000, monostearate polypropylene glycol 2000, ethoxylated propylene glycol monostearate, mono- and diesters of glycerol and fatty acids, polyglycerol fatty acid esters, ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol distearate, polyoxyethylene fatty acid polyhydric alcohol esters bat and fatty acids and polyoxyethylene sorbitol fatty acid esters are satisfactory esters of polyhydric alcohols.

(4) Waxy esters such as beeswax, spermaceti, myristyl myristate, stearyl stearate and arachidyl behenate.

(5) Sterol esters, examples of which are cholesterol esters of fatty acids.

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

Humectants such as polyols can also be used as cosmetically acceptable carriers in the compositions of the present invention. A humectant helps increase the effectiveness of the emollient, reduces skin dryness and improves the feel of the skin. Typical polyhydric alcohols include glycerin, polyalkylene glycols, and more preferably alkylene polyols and their derivatives, including 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 glycerin, propoxylated glycerin and mixtures thereof. The amount of humectant may be from 0.5 to 30%, preferably from 1 to 15% by weight, relative to the weight of the composition.

In addition, thickeners can be used as part of the cosmetically acceptable carrier of the compositions of the present invention. Typical thickeners include crosslinked acrylates (eg, Carbopol 982), hydrophobically modified acrylates (eg, Carbopol 1382), cellulose derivatives and natural gums. Useful cellulose derivatives include sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, ethylcellulose and hydroxymethylcellulose. Natural gums suitable for the present invention include guar gum, xanthan gum, sclerotia gum, carrageenan gum, pectin and combinations of these gums. The amount of thickener can be from 0.0001 to 5%, usually from 0.001 to 1%, optimally from 0.01 to 0.5% by weight.

In total, water, solvents, silicones, esters, fatty acids, humectants and/or thickeners will constitute the cosmetically acceptable carrier in amounts of from 1 to 99.9%, preferably from 80 to 99% by weight.

To obtain a water-in-oil emulsion or an oil-in-water emulsion, an oil or an oily substance may be present along with the emulsifier, depending mainly on the average hydrophilic-lipophilic balance (HLB) of the emulsifier used.

Surfactants may also be present in the cosmetic compositions of the present invention. For leave-in products, the total surfactant concentration will be from 0.1 to 40%, preferably from 1 to 20%, optimally from 1 to 5% by weight, based on the weight of the composition. For rinse-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 active agents. Particularly preferred nonionic surfactants are those containing a C ₁₀ -C ₂₀ fatty alcohol or acidic hydrophobic substance condensed with from 2 to 100 moles of ethylene oxide or propylene oxide per mole of hydrophobic substance; C ₂ -C ₁₀ -alkylphenols condensed with from 2 to 20 moles of alkylene oxide; mono- and diesters of ethylene glycol and fatty acids; monoglyceride fatty acids; sorbitol, mono- and di-C ₈ -C ₂₀ fatty acids; block copolymers (ethylene oxide/propylene oxide); and polyoxyethylene sorbitan, as well as combinations thereof. Alkyl polyglycosides and fatty saccharide amides (eg, methyl gluconamides) are also suitable nonionic surfactants.

Preferred anionic surfactants include soap, alkyl ether sulfate and alkyl ether sulfonates, alkyl sulfates and alkyl sulfonates, alkyl benzene sulfonates, alkyl and dialkyl sulfosuccinates, C ₈ -C ₂₀ acyl isethionates, acyl glutamates, C ₈ -C ₂₀ alkyl ether phosphates, and combinations thereof.

The cosmetic compositions of the present invention optionally contain a foaming surfactant. By "foaming surfactant" is meant a surfactant that, when combined with water and mechanically stirred, produces bubbles or foam. The foaming surfactant should preferably be mild, meaning that it should provide sufficient cleansing or detergent action without being overly drying and should still meet the foaming criteria described above. The cosmetic compositions of the present invention may contain a foaming surfactant at a concentration of from about 0.01% to about 50%.

The compositions can be prepared in the form of solutions. Solutions typically include aqueous or organic solvents, such as 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), glycerin, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexaneriol, ethanol and mixtures thereof. One example of such solvents is an ethanol/polyethylene glycol mixture (80/20).

You can make a lotion from this solution. Lotions typically contain from about 1% to about 20% (for example, about 5% to about 10%) emollient(s) and from about 50% to about 90% (for example, about 60% to about 80%) water .

Another type of product that can be prepared from a solution is a cream. The cream typically contains from about 5% to about 50% (for example, from about 10% to about 20%) emollient(s) and from about 45% to about 85% (for example, from about 50% to about 75%) water . Another type of product that can be prepared from a solution is an ointment. The ointment may contain a simple base of animal, vegetable or synthetic oils or semi-solid hydrocarbons. The ointment may contain from about 2% to about 10% emollient(s) plus from about 0.1% to about 2% thickening agent(s). Examples of thickening agents include, but are not limited to, those described in the ICI Handbook (International Cosmetic Ingredient Dictionary and Handbook), pages 1693-1697.

In addition, the compositions described herein can be prepared as emulsions. If the carrier is an emulsion, from about 1% to about 10% (for example, from about 2% to about 5%) of the carrier contains emulsifier(s). Emulsifiers can be non-ionic, anionic or cationic. Examples of emulsifiers include, but are not limited to, those described in the ICI Handbook, pages 1673-1686.

Lotions and creams can be prepared as emulsions. Typically, such lotions will contain from 0.5% to about 5% emulsifier(s), wherein said creams will typically contain from about 1% to about 20% (e.g., about 5% to about 10%) emollient(s). funds); about 20% to about 80% (eg, 30% to about 70%) water; and about 1% to about 10% (eg, about 2% to about 5%) emulsifier(s).

One-way emulsion skin care preparations such as oil-in-water and water-in-oil lotions and creams are well known in the art and are useful in the compositions and methods described herein. Multiphase emulsion compositions, such as water-in-oil-in-water or oil-in-water-in-oil, can also be used in the compositions and methods described herein. In general, these single- or multi-phase emulsions contain water, emollients and emulsifiers as main ingredients.

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

To enhance skin absorption of active ingredients, one or more additional substances may be added to topical formulations, including, but not limited to, dimethyl sulfoxide, dimethyl acetamide, dimethylformamide, surfactants, azone (laurocapram), alcohol, acetone, propylene glycol and polyethylene glycol. In addition, physical techniques such as iontophoresis or sonophoresis can be used to enhance transdermal penetration.

The topical composition described herein contains a cosmetically effective component that produces the desired effect on the skin as described herein, and those ingredients necessary for use as a carrier, such as an emulsion, cream, ointment, aqueous solution , lotion or aerosol.

The carriers used in the compositions described herein can be in a variety of forms. These forms include emulsion vehicles, including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water and oil-in-water-in-silicone emulsions, cream, ointment, aqueous solution, lotion or aerosol. Said component will be distributed primarily in either the water or the oil/silicone phase depending on the water solubility/dispersibility of the component contained in the composition.

The dermatological compositions described herein may typically contain a derivative of any compound or composition described herein and, optionally, a polar solvent. Solvents suitable for use in the compositions described herein include any polar solvent capable of dissolving the derivative. Suitable polar solvents may include: water; alcohols (such as ethanol, propyl alcohol, isopropyl alcohol, hexanol and benzyl alcohol); high molecular weight alcohols (such as propylene glycol, polypropylene glycol, butylene glycol, hexylene glycol, maltitol, sorbitol and glycerin); and panthenol dissolved in glycerin, aromatic oils and mixtures thereof. In addition, mixtures of the listed solvents can be used. Typical polar solvents may be polyhydric alcohols and water. Examples of solvents may include glycerin, panthenol in glycerin, glycols such as propylene glycol and butylene glycol, polyethylene glycols, water, and mixtures thereof. Additional polar solvents suitable for use may include alcohols, glycerin, panthenol, propylene glycol, butylene glycol, hexylene glycol, and mixtures thereof.

In addition, an emollient may be added to the cosmetic/dermatological compositions described herein. The emollient may contain fats, oils, fatty alcohols, fatty acids and esters that promote application and adhesion, impart shine and provide occlusive hydration. Suitable emollients 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, tocopheryl linoleate, germ glycerides wheat, arachidyl propionate, myristyl lactate, decyl oleate, propylene glycol ricinoleate, isopropyl linoleate, pentaerythrityl tetrastearate, neopentyl glycol dicaprylate/dicaprate, hydrogenated coco-glycerides, isononyl isononanoate, isotridecyl isononanoate, myristyl myristate, triisocetyl citrate, cetyl alcohol, tildodecanol, oleyl alcohol, panthenol, lanolin alcohol, linoleic acid, linolenic acid, sucrose esters of fatty acids, octylhydroxystearate and mixtures thereof. Suitable emollients may include polar emollient emulsifiers (such as linear or branched chain polyglycerol esters) and non-polar emollients. The emollient component can typically range from about 1% to about 90%, preferably from about 10% to about 80%, more preferably from about 20% to about 70%, and most preferably from about 40% to about 60%, relative to the cosmetic composition.

By “polar emollient” as used herein is meant any emollient emulsifier containing at least one polar moiety, wherein the solubility (at 30° C.) of the cytoprotective derivative compound in such polar emollient is greater than about 1.5%, preferably greater than about 2% %, more preferably greater than about 3%. Suitable polar emollients may include, but are not limited to, esters and ethers of high molecular weight alcohols, such as straight and branched chain polyglycerol esters and ethers. Non-limiting examples of such emollients may include polyglyceryl (PG)-3-diisostearate, polyglyceryl 2-sesquiisostearate, polyglyceryl 5-distearate, polyglyceryl 10-distearate, polyglyceryl 10-diisostearate, acetylated monoglycerides, glycerol esters, glycerol tricaprylate/ tricaprate, glyceryl ricinoleate, glyceryl isostearate, glyceryl myristate, glyceryl linoleate, polyalkylene glycols such as PEG 600, monoglycerides, 2-monolaurin, sorbitan esters and mixtures thereof.

As used herein, “non-polar emollient” means any emollient emulsifier that has no or minimal constant electrical torques. Suitable non-polar emollients may include, but are not limited to, esters and straight-chain and branched-chain hydrocarbons. Non-limiting examples of such emollients may include isononyl isononanoate, isopropyl isostearate, octyl hydroxy stearate, diisopropyl dimerate, lanolin oil, octyl palmitate, isopropyl palmitate, paraffins, isoparaffins, acetylated lanolin, sucrose fatty acid esters, isopropyl myristate, isopropyl stearate, mineral oil, silicone oils, , allantoin, isohexadecane, isododecane, petrolatum and mixtures thereof. The solubility of a compound in polar or non-polar emollients can be determined according to methods known in the art.

Suitable oils include esters, triglycerides, hydrocarbons and silicones. They may be a single component material or a mixture of one or more materials. These oils can typically range from 0.1% to about 100%, preferably from about 5% to about 90%, and most preferably from about 70% to about 90%, based on the emollient component.

Oils suitable for use herein may be acetylglycerides, octanoates and decanoates of alcohols and polyalcohols such as glycol and glycerol alcohols, ricinoleates of alcohols and polyalcohols such as cetyl ricinoleate, polyglyceryl 3diisostearate, polyglycerol ethers, polyglycerol esters, caprylic triglycerides, capric triglycerides, isostearic triglycerides, adipic triglyceride, phenyl trimethicone, lanolin oil, polybutene, isopropyl palmitate, isopropyl isostearate, cetyl ricinoleate, octyldodecanol, oleyl alcohol, hydrogenated vegetable oils, castor oil, modified lanolins, octyl palmitate, lanolin oil, einated soybean oil, cetyl ricinoleate, glyceryl trioctanoate, diisopropyl dimerate, synthetic lanolin derivatives and branched chain alcohols, sucrose fatty acid esters, octyl hydroxystearate and mixtures thereof.

Said oils used may preferably be selected such that a majority (at least about 75%, preferably at least about 80%, and most preferably at least about 99%) of the oils used have solubility parameters not differing by more than about 1 to about 0.1, preferably from about 0.8 to about 0.1.

A surfactant may also be added to the compositions described herein to provide cosmetic or consumer benefits. Surfactants suitable for use may be those that can form emulsions and/or associated structures. The surfactant emulsifier may be from 0% to about 20% relative to the composition, preferably from 0% to about 15%, and most preferably from about 1% to about 10%.

Examples of surfactants that can be used in the compositions described herein include sodium alkyl sulfates, e.g., sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acylsarcosinates, e.g., sodium N-lauroyl sarcosinate and sodium N-myristoyl sarcosinate, sodium dodecylbenzenesulfonate, sodium hydrogenated coconut oil fatty acid monoglyceride sulfate, sodium lauryl sulfoacetate and N-acyl glutamates, eg N-palmitoyl glutamate, sodium N-methylacyl taurine, sodium N-methyl acylalanine, sodium alpha-olefin sulfonate and sodium dioctyl sulfosuccinate; N-alkylaminoglycerols, for example N-lauryl-diamino-ethylglycerol and N-myristyldiaminoethylglycerol, N-alkyl-N-carboxymethylammonium betaine and 2-alkyl-1-hydroxyethylimidazoline sodium betaine; polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyoxyethylene lanolin alcohol, polyoxyethylene glyceryl monoaliphatic acid ester, polyoxyethylene sorbitan aliphatic acid ester, polyoxyethylene aliphatic acid ester, glycerol higher aliphatic acid ester, sorbitan aliphatic acid ester, Pluronic surfactant and polyoxyethylene sorbitan aliphatic acid esters such as polyoxyethylene sorbitan monooleate and polyoxyethylene sorbitan monolaurate. The compositions described herein may use emulsifier-type surfactants known to those skilled in the art.

Also suitable for use in the present invention may be surfactants that form associated structures, preferably layered or hexagonal liquid crystals, at ambient temperature when mixed with a polar solvent. When preparing a test combination of a surfactant and a polar solvent to demonstrate the ability to form associated structures, the surfactant must be sufficiently soluble in the polar solvent so that the associated structure can form at ambient temperature.

Any surfactant that forms associated structures at ambient temperature and is suitable for use in cosmetics may be suitable for use in the present invention. 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.

Surfactants can be used at levels from about 4% to about 97%, preferably from about 5% to about 95%, more preferably from about 20% to about 90%, and most preferably from about 30% to about 70% relative to associated structures.

The cosmetic compositions described herein may contain one or more materials, referred to herein individually or collectively as “curing agents,” that effectively cure the specific liquid base materials used in the cosmetic composition. (As used herein, the term “solidify” refers to the physical and/or chemical change of a liquid base material to produce a solid or semi-solid under ambient conditions, i.e., to produce a final composition that has a stable physical structure and that can be applied to the skin under normal conditions of use.) As will be appreciated by those skilled in the art, the selection of a particular hardener for use in cosmetic compositions will depend on the particular type of composition desired, i.e., gel or wax based, the rheological properties required, the liquid used base material and other materials used in the composition. The hardener may preferably be present at a concentration of from about 0.1% to about 90%, more preferably from about 1% to about 50%, even more preferably from about 5% to about 40%, most preferably from about 3% to about 20% .

The various wax-based lipstick embodiments described herein may preferably contain from about 5% to about 50% (by weight) of a wax hardener. As used herein, the term “wax hardener” refers to a hardening material with wax-like properties. Such waxy materials can also serve as emollients. Wax materials used herein include high melting point waxes, i.e., having a melting point of about 65°C to about 125°C, such as beeswax, spermaceti, carnauba wax, waxwort, candelilla wax , montan wax, ozokerite, ceresin, paraffin, synthetic waxes such as Fischer-Tropsch waxes, microcrystalline wax and mixtures thereof. Ceresin, ozokerite, white beeswax, synthetic waxes and mixtures thereof are waxes useful in the present invention. Low melting waxes with a melting point of about 37°C to about 75°C may be preferred for use in the various lipstick embodiments described herein. Wax variants 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 containing fatty acid chains of about 8 to about 30 carbon atoms, and mixtures thereof. Waxy materials include cetyl alcohol, palmitic acid, stearyl alcohol, behenamide, sucrose tallow fatty acid esters, mono- and di-fatty acid esters and polyethylene glycol, and mixtures thereof. Mainly used are stearyl alcohol, cetyl alcohol and their mixtures. Additional fatty acids, fatty alcohols and other waxy materials are also well known in the art.

In addition, these compositions may include other cosmetics, carriers, adjuvants and the like. Some specific additional products may include sunscreen; retinoids; antioxidants; hydroxy acids; fatty acids, suitable non-toxic metal salts of natural amino acids or hydroxyalkyl acids; plant extracts, salicylic acid, benzoyl peroxide, antibiotics, antiandrogens, anti-inflammatory agents, antioxidants, ascorbic acid, B vitamins, tocopherols or tocotrienols, corticosteroids, humectants, surfactants, keratolytic agents, complexing agents, dyes, fragrances and mixtures thereof .

Synthetic methods

The resorcinol compounds described herein can be synthesized using a suitable combination of generally well known synthetic methods. Methods applicable to the synthesis of the compounds proposed in the invention are both obvious and accessible to those skilled in the relevant field of technology in light of the ideas described herein.

4-Alkylresorcinols are available from Sigma-Aldrich, St. Louis, MO, USA.

EXAMPLES

EXAMPLE 1

[0100] Evaluation of signs of degradation and stabilization of 4-alkylresorcinols

[0101] Color measurements

[0102] 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 form a clear, colorless, homogeneous solution. One portion of each solution (5 ml) was added to a 20 ml scintillation vial containing either Niacinamide (B3) (50 mg), AceMet (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 assessed visually and L*a*b* values were experimentally determined using a Labscan XE instrument (Hunter Associates Labs Inc., Reston, VA) and processed using Universal Software (version 4.10). The L* parameter determines darkness and lightness and ranges from black (L* = 0) to white (L* = 100). The a* parameter determines the color content and color intensity in the range from green (a* < 0) to neutral gray (a* = 0) and red (a* > 0). The b* parameter also determines the color content and color intensity in the range from blue (b* < 0) to neutral gray (b* = 0) and yellow (b* > 0).

[0103] Quantitative determination of 4-alkylresorcinol

The amount of 4-alkylresorcinol present in each of the samples used for color measurements was determined after 2 weeks at room temperature (~20-22°C) using high-performance liquid chromatography (HPLC). An aliquot of sample (100 μL) from each of the color measurement solutions was diluted with deionized water:acetonitrile (1:1, 900 μL) to obtain test samples (1 mL). An aliquot (10 µl) from each test sample was injected into a Waters 2695 separation module, chromatographed and separated on a Restek Pinnacle DB C18 column (5 µm, 4.6 x 150 mm) operating at 30°C, and monitored for 4-alkylresorcinols using a set of detectors with a Waters 2996 photodiode array at 281 nm. The mobile phase consisted of water (A) and acetonitrile (B), with optimal separation achieved by applying a gradient of 95:5 (A:B) to 5:95 (A:B) over 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 4-alkylresorcinols at concentrations 1.5 times higher and 5 times lower were freshly prepared and analyzed immediately; standard curves were generated over the range of samples studied and linearity was confirmed.

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

[0104] 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". The freshly prepared HR solution was colorless and no degradation of HR was observed by HPLC analysis. After 2 weeks, the color of the HR solution changed to a reddish pink, as evidenced by an increase in components a* and b* (as well as a decrease in L*), while the HR level decreased by 40%. The addition of B3 to the HR solution significantly accelerated the degradation of HR by 55% and resulted in a more intense color, as evidenced by a further significant increase in a*, b* and a decrease in L*. In contrast, surprisingly, the addition of AceMet to the HR solution significantly inhibited the color change and degradation of HR in the presence or absence of B3, as evidenced by the corresponding L*a*b* values and HR content, which were very close to control levels. Likewise, AceMet significantly inhibited color change in ER solutions in the presence or absence of B3 and provided protection against ER degradation, although to a lesser extent compared with HR. The results obtained clearly demonstrated the significant benefits of AceMet in terms of color and chemical stabilization of 4-alkylresorcinols in the presence or absence of other cosmetic ingredients (such as B3) that may further accelerate such discoloration and degradation.

[0105] 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) is shown in the table below:

TABLE 1. EXAMPLES Sample ^a Appearance ^b L* a* b* 4-Alkylresorcinol (% of control sample) ^c 1 Control sample colorless 98 0 0 100 2 1% HR reddish pink 84.77 11.4 13.4 60 3 1% HR + 1% B3 orange 80.87 17.97 36.52 45 4 1% HR + 1% AceMet almost colorless 94.61 -0.85 2.32 107 5 1% HR + 1% B3 + 1% AceMet almost colorless 94.61 -0.85 2.32 106 6 1% ER light orange 82.74 6.38 39.57 96 7 1% ER + 1% B3 yellow-orange 78.81 7.33 39.31 90 8 1% ER + 1% AceMet almost colorless 94.61 -0.85 2.32 102 9 1% ER + 1% B3 + 1% AceMet almost colorless 94.61 -0.85 2.32 102

[0106] ^a Control sample = deionized water:butylene glycol (4:1).

[0107] ^b Appearance of the solution after 2 weeks.

[0108] ^c Determined by HPLC analysis.

EXAMPLE 2 ER and AceMet

A cosmetic composition for topical application was prepared within the scope of the present invention.

The base formulation shown in the table below was prepared by heating the phase A ingredients to 70-85°C while stirring. The phase B ingredients were heated in a separate container to 70 to 85°C with stirring. Phase A was then added to phase B, with both phases maintained at a temperature of 70 to 85°C. The mixture was stirred for at least 15 minutes at a temperature of from 70 to 85°C, then cooled. Phase C ingredients were added at 50°C followed by phase D ingredients at 40°C.

EXAMPLE 3

An additional cosmetic composition falling within the scope of the present invention was prepared as shown in the table below.

Table 3 wt.% Phase Water, deionized The basis A Disodium EDTA 0.05 A Magnesium aluminum silicate 0.6 A Methylparaben 0.15 A Simethicone 0.01 A 1,3-Butylene glycol 3.0 A Hydroxyethylcellulose 0.5 A Glycerin, USP purity 2.0 A Xanthan gum 0.2 A Triethanolamine 1.2 B Stearic acid 3.0 B Propylparaben, purity according to the National Formulary 0.1 B Glyceryl hydroxystearate 1.5 B Stearyl alcohol 1.5 B Isostearyl palmitate 6.0 B C _12-15 alcohols octanoate 3.0 B Dimethicone 1.0 B Cholesterol, purity according to the National Formulary 0.5 B Sorbitan stearate 1.0 B Flavoring components 1.0 B Tocopheryl acetate 0.1 B PEG-100 stearate 2.0 B Sodium stearoyl lactylate 0.5 B Hydroxycaprylic acid 0.1 C 4-Cyclohexylresorcinol 10.0 C AceMet 0.001 D Butyloxytoluene 0.10 C Niacinamide 0.05 C alpha-Bisabolol 0.2 C

The composition was prepared as follows:

1. Heat phase A to 80°C with stirring.

2. Heat phase B to 75°C in a separate container with stirring.

3. Add B to A and stir while heating is maintained at 70 to 80°C for 15 minutes; then turn off the heat and continue stirring for another 15 minutes.

4. At 50°C, add phase C and stir for 10 minutes.

5. At 40°C, add phase D and stir for 10 minutes.

EXAMPLES 4-11

A number of additional compositions within the scope of the present invention were prepared by the method described in Example 2 and are listed below in the table.

TABLE 4. HR and AceMet Ingredients Phase Examples (wt.%) 4
Sour soap base 5 6 7 8 9 10 eleven Stearic acid A 17.9 17.9 17.9 17.9 17.9 17.9 17.9 17.9 Sodium cetearyl sulfate A 2.2 1 1.5 2 3 2 Myrj 59 A 2 2 2 2 2 1 Propylparaben A 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Disodium EDTA A 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Span 60 A 2 2 2 2 2 1 Butyloxytoluene C 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 4-Hexylresorcinol C 0.05 0.05 2.0 2.0 3.5 3.5 5.0 10.0 AceMet D 0.001 0.001 0.01 0.01 0.5 0.5 0.001 0.01 CON, 22% B 2.20 Glycerol B 1 1 1 1 1 1 1 1 Methylparaben B 0.15 0.15 0.15 0.15 0.15 0.15 0.15 0.15 Water B The basis The basis The basis The basis The basis The basis The basis The basis

EXAMPLE 12

The compositions in the table below were prepared in accordance with the method outlined in Example 1 above.

Table 5: Formulations for skin lotions 1 2 3 4 5 Raw material wt.% wt.% wt.% wt.% wt.% Stearic acid A 17.90 17.90 17.90 17.90 17.90 Cetostearyl alcohol A 0.53 0.53 0.53 0.53 0.53 Dimethicone (DC200, 350 cS) A 0.50 0.50 0.50 0.50 0.50 Parsol MCX A 1.25 1.25 1.25 1.25 1.25 Parsol 1789 A 0.40 0.40 0.40 0.40 0.40 Propylparaben A 0.10 0.10 0.10 0.10 0.10 Water B 55.88 55.88 55.88 55.88 55.88 Glycerol B 1.00 1.00 1.00 1.00 1.00 EDTA B 0.04 0.04 0.04 0.04 0.04 Methylparaben B 0.20 0.20 0.20 0.20 0.20 CON, 22% B 2.20 2.20 2.20 2.20 2.20 AceMet D 1.0 1.0 1.0 1.0 1.0 Niacinamide C 1.00 1.00 - - 1.00 Butyloxytoluene C 0.10 - - - - 4-Ethylresorcinol C 2.00 3.55 - - - 4-Hexylresorcinol C - - 5.00 - - 4-Cyclohexylresorcinol C - - - 2.84 6.00 In sufficient quantities up to 100% water In sufficient quantities In sufficient quantity In sufficient quantities In sufficient quantities In sufficient quantity

Claims (19)

1. Cosmetic composition for topical application, containing: a) from 0.00001 to 10 wt.% N-acetylmethionine; b) from 0.00001 to 10% by weight of one or more 4-substituted resorcinol derivatives of general formula I: (I), 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 represents ethyl; And c) a cosmetically acceptable carrier. 2. The composition according to claim 1, wherein both R ₁ and R ₂ are H. 3. Cosmetic composition according to any one of paragraphs. 1, 2, additionally containing an agent that has a beneficial effect on the skin, selected from the group consisting of alpha hydroxy acids and their esters, beta hydroxy acids and their esters, polyhydroxy acids and their esters, kojic acid and its esters, ferulic acids and ferulate derivatives, vanillic acid and its esters, dicarboxylic acids and their esters, retinol, retinal, retinyl esters, hydroquinone, tert-butylhydroquinone, 1-methylnicotinamide chloride and mixtures thereof. 4. Stabilized cosmetic composition containing: a) 4-ethylresorcinol stabilized with N-acetylmethionine; b) optionally an agent having a beneficial effect on the skin; And c) a cosmetically acceptable carrier; wherein said N-acetylmethionine is present in an amount from 0.0001 to 5 wt.% relative to the weight of said cosmetic composition; And wherein the mass ratio of said N-acetylmethionine to said 4-ethylresorcinol is from 10,000:1 to 1:100,000. 5. A method of stabilizing 4-ethylresorcinol or 4-hexylresorcinol in a composition containing a cosmetically acceptable carrier by adding to the composition N-acetylmethionine in an amount sufficient to stabilize said 4-ethylresorcinol or 4-hexylresorcinol, wherein said N-acetylmethionine is present in an amount from 0.0001 to 5 wt.% relative to the weight of said cosmetic composition; And wherein the mass ratio of said N-acetylmethionine to said 4-substituted resorcinol derivative is from 10,000:1 to 1:100,000. 6. The use of N-acetylmethionine and 4-ethylresorcinol in the preparation of a cosmetic composition for topical application.