RU2785545C2 - Methods for improvement of retinoid activity - Google Patents

Abstract

FIELD: cosmetology.

SUBSTANCE: invention relates to a method for treatment of the skin requiring treatment with retinoids. The method for treatment of the skin sequentially includes: (a) cleansing of the skin requiring elimination of signs of skin aging, acne, or rosacea, using a cleansing composition containing low-molecular hydrophobically-modified polymer, which is potassium acrylate copolymer; and (b) local application to the skin of the retinoid-containing composition remaining on the skin.

EFFECT: invention allows for an increase in retinoid activity.

3 cl, 3 tbl, 2 ex

Description

Scope of the invention

The present invention relates to methods for treating skin requiring treatment with retinoids, which include cleansing the skin with a cleansing composition containing a low irritant polymeric cleansing agent prior to treatment with retinoids. These methods improve the activity of retinoids and can provide excellent results.

Prerequisites for the creation of the invention

Retinoids are used in a variety of topical prescription and cosmetic formulations to address skin conditions such as signs of skin aging, acne, and rosacea.

For example, tretinoin is used in prescription acne medications as well as prescription anti-wrinkle medications such as RENOVA® available from Obagi Medical Products, Inc. Retinol is used in cosmetic products such as NEUTROGENA® Rapid Wrinkle Repair® available from Johnson & Johnson Consumer Inc. NEUTROGENA® Rapid Wrinkle Repair® is used to reduce the appearance of skin wrinkles, smooth fine lines, improve skin texture and brighten skin tone. In particular, retinol has proven to be a highly effective and economical cosmetic ingredient, and improvement in its activity and delivery to the skin is always desirable.

Applicants have now found that pre-treatment of the skin by cleansing with a cleansing composition containing specific low irritant polymeric cleansing agents (LIPCAs) prior to topical application of a retinoid unexpectedly increases the activity of the retinoid.

Multi-stage skin care regimens are known. For example, WO 2010/085753 describes a treatment regimen comprising cleansing at least a portion of a rosacea-affected area of the skin with a cleanser; applying the metronidazole-containing composition to at least a portion of the affected area; and applying the anti-redness composition to at least a portion of the cleaned and treated metronidazole area. CETAPHIL® (Galderma Laboratories) and NU-DERM® (Obagi Medical Products, Inc.) "mild action" skin cleansers are described. In addition, the optional application of compositions containing retinoids and other ingredients is described.

The instructions on the NEUTROGENA® Rapid Wrinkle Repair® package also state that the product should be applied to cleansed skin, although no specific cleanser is indicated.

It may also be noted that a cleansing composition containing LIPCA, a copolymer of potassium acrylates, is available from Johnson & Johnson Consumer Inc. as an ultra-soft cleanser for daily use of NEUTROGENA®.

Statement of the Invention

The invention provides a method of treating the skin, comprising sequentially: (a) cleansing skin requiring the elimination of signs of skin aging, acne or rosacea, using a cleansing composition containing a superhydrophilic amphiphilic copolymer (SAC); and (b) topical application to the skin of a retinoid-containing composition remaining on the skin.

The invention also encloses a kit containing: (a) a cleansing composition containing CAC; and (b) a retinoid-containing composition remaining on the skin.

The invention further provides a method for enhancing retinoid activity, comprising cleansing skin requiring retinoid treatment with a CAC-containing cleansing composition prior to bringing the skin into contact with the retinoid.

The invention also provides a method for treating skin, comprising in sequence: (a) cleansing skin requiring the elimination of signs of skin aging, acne or rosacea, using a cleansing composition containing a low molecular weight hydrophobically modified polymer (HMP); and (b) topical application to the skin of a retinoid-containing composition remaining on the skin.

The invention also encloses a kit containing: (a) a cleansing composition containing a low molecular weight GMF; and (b) a retinoid-containing composition remaining on the skin.

The invention further provides a method for enhancing retinoid activity, comprising cleansing skin requiring retinoid treatment with a cleansing composition containing a low molecular weight GMP prior to bringing the skin into contact with the retinoid.

Detailed description of the invention

Unless otherwise indicated, all technical and scientific terms used in this document have the common meaning understood by any average specialist in the field to which the present invention pertains. All publications, patent applications, patents and other references mentioned in this document are incorporated herein by reference.

As used herein, the term "topical application" means direct application or distribution to the outer surface of the skin, scalp, or hair, for example, by hand or using an applicator such as a tissue, roller, or spray.

As used herein, the term "cosmetic" refers to an appearance-enhancing substance or preparation that maintains, restores, imparts, mimics or enhances physical attractiveness, or has an attractive or youthful effect, especially with respect to the appearance of tissue or skin.

As used herein, the term "cosmetically effective amount" means an amount of a physiologically active compound or composition sufficient to reverse one or more signs of skin aging, but low enough not to cause serious side effects. The cosmetically effective amount of a compound or composition will vary depending on the particular condition being treated, the age and physical condition of the end user, the severity of the condition being treated/prevented, the duration of treatment, the nature of other treatment options, the particular compound or product/composition employed, the specific cosmetically acceptable carrier used; and the like.

As used herein, the term "cosmetically acceptable" means that the ingredients that the term describes are acceptable for use in contact with tissues (e.g., skin or hair) without undesirable toxicity, incompatibility, instability, irritation, allergic reactions or the like.

As used herein, the term "cosmetically acceptable active agent" means a compound (synthetic or natural) that has a cosmetic or therapeutic effect on the skin or hair.

As used herein, the term "treatment" refers to reducing, ameliorating, preventing, correcting, or eliminating the symptoms of, or presence of, a condition or disorder.

The present invention is suitable for reversing signs of skin aging. As used herein, the term "signs of skin aging" refers to the presence of folds and wrinkles, loss of elasticity, uneven skin tone, and patchiness. In a particularly preferred embodiment, a sign of aging is the presence of folds, wrinkles and/or loss of elasticity.

As used herein, the term "wrinkle" includes fine lines, fine lines, or deep lines. Examples of wrinkles include, but are not limited to, fine lines around the eyes (eg, crow's feet), wrinkles on the forehead and cheeks, frown lines, and expression lines around the mouth.

As used herein, the term "loss of elasticity" refers to loss of elasticity or integrity of a skin or tissue structure, including, without limitation, tissue sagging, laxity, and laxity. Loss of elasticity or integrity of the tissue structure may result from a number of factors, including, but not limited to, disease, aging, hormonal changes, mechanical trauma, environmental stress, or may result from the application of products such as cosmetics or pharmaceuticals to the tissue.

As used herein, the term "uneven skin tone" means a skin condition associated with diffuse or patchy pigmentation, which can be considered hyperpigmentation, such as post-inflammatory hyperpigmentation.

As used herein, the term "spotting" refers to a skin condition associated with redness or erythema.

The invention is also applicable to the treatment of acne. As used herein, the term "acne" refers to disorders resulting from the effects of hormones and other substances on the sebaceous glands and hair follicles, usually resulting in clogged pores and the formation of inflammatory or non-inflammatory skin lesions. This applies in particular to blemishes, lesions or pimples, pimple precursors, blackheads and/or comedones. As used herein, the term “pimple precursor” means an inflamed follicle that is not visually identifiable on the skin surface with the naked eye (eg, as is the case with a lesion).

The invention is also applicable to the treatment of rosacea. As used herein, the term "rosacea" means skin with persistent erythema with or without papules, pustules, or nodules.

Unless otherwise indicated, a percentage or concentration is indicated as a percentage or concentration by weight (i.e., % w/w). Unless otherwise noted, all ranges are subject to limit values, for example, the range "4 to 9" includes limits 4 and 9.

Where appropriate, chemicals are listed according to the International Nomenclature for Cosmetic Ingredients (INCI) names. Additional information, including vendors and trade names, can be found in the relevant INCI monograph in the International Cosmetic Ingredient Dictionary and Handbook, 16th ^Edition , published by the Personal Care Council, Washington, DC, USA, or online in the Knowledge Base. Personal Care Council data at http://online.personalcarecouncil.org/jsp/Home.jsp.

Cleansing composition

In accordance with the invention, prior to treating the skin with a retinoid, the skin is cleansed with a cleansing composition containing a low irritant polymeric cleansing agent (LIPCA).

In one embodiment, LIPCA contains at least one superhydrophilic amphiphilic copolymer (SAC).

Suitable CACs and cleaning compositions containing them suitable for use in the invention are described, for example, in US 8,258,250, the description of which is incorporated herein by reference.

Synthetic methods for the preparation of the CAS of the present invention include post-polymerization modification of superhydrophilic repeating-containing precursor polymers to produce some repeating units with amphiphilic properties. Non-limiting examples include the reaction of superhydrophilic polymers consisting of repeating units containing multiple hydroxyl functional groups, e.g. sucrose), with reagents, as a result of which amphiphilic repeating units are formed. Examples of acceptable reaction schemes include:

i) esterification with alkenyl succinic anhydrides,

ii) esterification with 1,2-epoxyalkanes,

iii) esterification with 3-chloro-2-hydroxypropylalkyldimethylammonium chlorides, and

iv) esterification with monoalkyl phosphate esters.

In accordance with certain preferred embodiments, the CAC for use in the present invention is a polymer having a plurality of hydroxyl functionalities that is post polymerized modified to effect the transition of some of the repeat units to amphiphilic repeat units. In one particularly preferred embodiment, a polymer, for example a starch, such as a polymer of starch and dextrin, is esterified with alkenyl succinic anhydride to effect the conversion of some of the superhydrophilic anhydroglucose units to ARU. The structure of one of the acceptable CACs resulting from this reaction may be sodium C-6 dextrin alkenyl succinate as shown below:

.

.

For example, the CAC may be sodium dextrin dodecenyl succinate if R=C ₁₂ H ₂₃ . One skilled in the art will appreciate that such alkenyl succinic acid esters of polysaccharides can be synthesized as described, for example, in US Pat. No. 2,661,349, incorporated herein by reference. Depending on the nature of the reaction conditions, molecular architecture, type of sugar repeat units, branching points and molecular weight, modification of the sugar repeat units (anhydroglucose units) can also occur at the C-2, C-3 or C-4 positions, in addition to the one shown above position C-6.

CAS obtained by reacting the original polysaccharide with a hydrophobic reagent contains a polysaccharide associated with a hydrophobic reagent. In certain preferred embodiments of this invention, the CAC is a starch-based polysaccharide modified with one or more hydrophobic reagents.

Examples of suitable starches include those derived from plants such as corn, wheat, rice, tapioca, potatoes, sago, and the like. Such starches may be obtained from natural plant species, or bred through breeding or genetic modification. In one embodiment of the present invention, starches include both waxy derivatives of such starches (less than 5% amylose), high amylose starches (greater than 40% amylose), and chain length modified starches (e.g., the starches described in US Patent No. 5,954,883, the description of which is incorporated herein by reference in its entirety) and/or combinations thereof.

In certain preferred embodiments, the starting starch is potato or tapioca starch. In certain other preferred embodiments, the starting starch is waxy potato starch or waxy tapioca starch. In certain embodiments, the starch-based polysaccharide is modified by dissolving such a low molecular weight starch or "dextrin" in water and reacting such starch with a hydrophobic reagent. It is desirable to treat starch to reduce its molecular weight by methods known in the art, such as acid and heat, enzyme treatment, or heat treatment.

It is desirable that the viscosity of the aqueous solution of the polymeric surfactant (surfactant) be low to minimize the adverse effects of high levels of surfactant substance when pumping or draining the solution. Therefore, in one embodiment of this invention, the Brookfield viscosity, as measured at room temperature (about 23° C.) at 200 rpm using a No. 3 spindle for the polymeric surfactants of this invention, may be less than about 1000 cP at 10% content of substances based on the total weight of the solution. In another embodiment, the Brookfield viscosity, as measured at room temperature (about 23° C.) at 200 rpm using a No. 3 spindle in a 10% aqueous solution, may be less than about 25 cps. In yet another embodiment, the Brookfield viscosity, as measured at room temperature (about 23° C.) at 200 rpm using a No. 3 spindle in a 10% aqueous solution, will be less than about 10 centipoise.

In certain preferred embodiments, the starch-based polysaccharide is modified with alkenyl succinic anhydride. Surprisingly, substituted succinic anhydride containing a C ₁₂ or longer side chain has been found to provide more foam volume and foam stability than substituted succinic anhydrides with a side chain of less than C ₁₂ . In certain preferred embodiments, the alkenyl succinic anhydride is dodecenyl succinic anhydride (DDSA). Approximate levels of DDSA treatment, based on the dry weight of the small molecule, range from about 3% to about 25%. In another embodiment, the treatment level may be from about 5% to about 15% DDSA, based on the dry weight of the low molecular weight starting starch.

In one embodiment of the present invention, the CAC is derived from the reaction of a parent polysaccharide and DDSA, and the bound DDSA on the starch-based polysaccharide may be from about 3% to about 15% by weight of dry starch. In another embodiment, the bound DDSA is 5 to 12% based on the dry weight of the starch.

In one embodiment, the hydrophobic reagent is a highly branched DDSA derivative containing a side chain of 12 carbon atoms obtained from propene tetramerization. It has been found that when tetrapropene is subsequently introduced into an ene reaction with maleic anhydride, highly branched tetrapropenyl succinic anhydride (TPSA) is formed. Because this material is a slightly viscous oil and has an acceptable solubility in water (eg, about 2-5% in water at 23° C.), this reagent is able to successfully react with the low molecular weight polysaccharide. Therefore, in an embodiment of the present invention, TPSA can be used as a hydrophobic reagent used to modify low molecular weight starch.

In certain other preferred embodiments, the starch-based polysaccharide is modified with a long chain quaternary compound in which at least one chain contains 3 or more carbon atoms. In another embodiment, the long chain quaternary compound has at least one chain containing 6 or more, and more preferably 12 or more carbon atoms, for example, 3-chloro-2-hydroxypropyldimethyldodecylammonium chloride (trade name QUAB® 342, from QUAB Chemicals) or the epoxy form of such a compound, 2,3-epoxypropyldimethyldodecylammonium chloride.

In a preferred embodiment, the CAC is a dodecenyl succinic anhydride modified potato or tapioca starch-based polysaccharide, wherein the CAC contains a mole percentage of amphiphilic units of at least 5% but less than 10% and a weight average molecular weight of less than about 200,000 .

In addition to starch-based polysaccharides, other polysaccharides are suitable for use in CAS. Such polysaccharides can be obtained from plant sources and from sources based on the repeating units of various sugars. Some non-limiting examples of such polysaccharides are guar, xanthan, pectin, carrageenan, locust bean gum and cellulose, including physically and chemically modified derivatives of these substances. In embodiments, physical, chemical, or enzymatic degradation of these materials may be required to reduce the molecular weight to the desired range to provide the viscosity required for the desired application. Chemical modification can also be performed to provide additional functional properties (e.g. cationic, anionic or non-ionic), such as treatment with propylene oxide (OP), ethylene oxide (OE), alkyl chlorides (alkylation) and esterification, such as 3-chloro-2-hydroxypropyl chloride -trimethylammonium, sodium tripolyphosphate, chloroacetic acid, epichlorohydrin, phosphorus oxychloride, etc.

In another embodiment, LIPCA contains at least one low molecular weight hydrophobically modified polymer (HMP).

Suitable low molecular weight GMPs and cleaning compositions containing them suitable for use in the invention are described, for example, in US 8,025,902, the description of which is incorporated herein by reference.

Examples of low molecular weight GMPs include low molecular weight acrylics, other ethylenically unsaturated polymers, polyesters, polycarbonates, polyanhydrides, polyamides, polyurethanes, polyureas, polyimides, polysulfones, polysulfides, combinations of two or more of these, and the like.

Examples of suitable low molecular weight acrylic polymers include hydrophobically modified acrylic, polysaccharide, cellulose and starch polymers, combinations of two or more of these, and the like. Suitable low molecular weight acrylic polymers include hydrophobically modified acrylic polymers, as well as other acrylic polymers, any of which can be formed as a solution, suspension, precipitate, dispersion, emulsion, inverse emulsion, microemulsion, by micellar polymerization methods, and a combination of two or more of these. Acrylic polymers for use in the present invention may be derived from any one or more monomers selected from the group consisting of (meth)acrylates, (meth)acrylamides, vinyl ethers, allyl ethers, esters and amides, amines , itaconates, crotonates, styrenes and olefins. Acrylic polymers may be composed of monomers that are non-ionic hydrophilic, non-ionic hydrophobic, anionic, cationic, zwitterionic, non-associative macromeric, associative macromeric, or multifunctional/cross-linked in nature.

As used herein, the term "low molecular weight polymer" refers to a polymer with a number average molecular weight (M _n ) of about 100,000 or less as measured by gel permeation chromatography (GPC) on a column calibrated against a poly(methyl methacrylate) (PMMA) reference sample. (As used herein, unless otherwise indicated, all number average molecular weight (M _n ) values refer to the molecular weight measured by gel permeation chromatography (GPC) on a column calibrated against a poly(methyl methacrylate) (PMMA) reference sample. ) In certain preferred embodiments, the implementation of low molecular weight polymers are polymers, the molecular weight of which is in the range of M _n from about 5000 to about 80,000, more preferably M _n from about 10,000 to about 50,000, and most preferably M _n from about 15 000 to 40,000.

Certain GMPs and methods for preparing such polymers are described in US Patent No. 6,433,061 to Marchant et al., the disclosure of which is incorporated herein by reference. The polymeric materials used in the present invention are preferably non-crosslinked linear acrylic copolymers which are very mild to the skin and mucosa. These non-crosslinked linear polymers are preferably low molecular weight having M _n 100,000 or less. The copolymer compound is obtained by polymerization of at least two monomeric components. The first monomeric component is selected from one or more α,β-ethylenically unsaturated monomers containing at least one carboxylic acid group. This acidic group can be derived from monobasic or dibasic acids, dicarboxylic acid anhydrides, dibasic acid monoesters and their salts. The second monomeric component is hydrophobically modified (compared to the first monomeric component) and is selected from one or more α,β-ethylenically unsaturated non-acidic monomers containing a C ₁ -C ₉ alkyl group, including linear and branched C ₁ -C ₉ alkyl esters (meth ) acrylic acid, vinyl esters of linear and branched C ₁ -C ₁₀ carboxylic acids and mixtures thereof. In one aspect of the present invention, the second monomeric component is represented by the formula:

_CH2 =CRX,

where R represents a hydrogen atom or methyl; X represents -C(O)OR ₁ or -OC(O)R ₂ ; R ₁ is linear or branched C ₁ -C ₉ alkyl; and R ₂ represents a hydrogen atom or linear or branched C ₁ -C ₉ alkyl. In another aspect of the present invention, R ₁ and R ₂ are linear or branched C ₁ -C ₈ alkyl, in an additional aspect, R ₁ and R ₂ are linear or branched C ₂ -C ₅ alkyl.

Preferably, the hydrophobically modified polymers comprise, consist essentially of, or consist of, low molecular weight, non-crosslinked, linear acrylic copolymers that are derived from at least one first monomeric component selected from the group consisting of (meth)acrylic acid and at least one second monomeric a component selected from the group consisting of one or more C ₁ -C ₉ alkyl(meth)acrylates, wherein the number average molecular weight of the low molecular weight copolymer is about 100,000 or less.

Examples of the first monomeric components include (meth)acrylic acid, itaconic acid, citraconic acid, maleic acid, fumaric acid, crotonic acid, aconitic acid, and mixtures thereof. Examples of the second monomer components include ethyl (meth) acrylate, butyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, vinyl formate, vinyl acetate, 1-methyl vinyl acetate, vinyl propionate, vinyl butyrate, vinyl 2-ethyl hexanoate, vinyl pivalate, vinyl neodecanoate, and mixtures thereof.

As used herein, the terms "(meth)acrylic acid" and "(meth)acrylate" are considered to include the corresponding methyl acrylic acid derivatives and the corresponding alkyl acrylate. For example, "(meth)acrylic acid" refers to acrylic acid and/or methacrylic acid, and the term "(meth)acrylate" refers to alkyl acrylate and/or alkyl methacrylate.

More preferably, said first monomeric component is selected from the group consisting of (meth)acrylic acid and said second monomeric component is selected from the group consisting of at least one C ₁ -C ₉ alkyl (meth)acrylate.

Non-crosslinked linear acrylic copolymer compounds can be synthesized by art-known free radical polymerization techniques. In one aspect of the present invention, the weight ratio of the first monomeric component to the second monomeric component is in the range of about 20:80 to about 50:50. In another aspect, the weight ratio of the first monomeric component to the second monomeric component is about 35:65, and in a further aspect the weight ratio of the first monomeric component to the second monomeric component is about 25:75.

Methods for the synthesis of polymers used in the compositions and methods of the present invention can be found in US patent No. 6,433,061, incorporated herein by reference.

The methods and compositions of the present invention can use linear copolymer materials that preferably have a viscosity of 500 mPa·s or less (measured on a Brookfield RVT series viscometer, 20 rpm, No. 1 spindle) at a concentration of 5% wt. polymeric substances in deionized water and neutralized to pH 7 with a NaOH solution with a concentration of 18% of the mass. In another aspect, the viscosity value may range from about 1 to about 500 mPas, in a further aspect, from about 10 to about 250 mPas, and in yet another aspect, from about 15 to about 150 mPas.

In one embodiment, the low molecular weight HMF is a non-crosslinked linear acrylic copolymer having a number average molecular weight of from about 15,000 to about 40,000 and is made from methacrylic acid and ethyl acrylate.

In another embodiment, the low molecular weight GMF is a copolymer of potassium acrylates.

In addition to LIPCA, i.e. The CAC or GMP cleansing composition may optionally contain additional ingredients typically used in cleansing compositions. A wide range of additional ingredients conventionally used in skin and hair care compositions may also be included at art-established concentrations. For example, the cleansing composition may contain other polymeric surfactants or monomeric surfactants. Anionic, nonionic, amphoteric, cationic surfactants known in the art, or mixtures of the foregoing, can be used. Other optional ingredients include perlescent agents or opacifiers, thickeners, emollients, secondary conditioners, humectants, chelating agents, scrubs, and additives that enhance the look, feel, or fragrance of the cleansing composition, such as colorants, fragrances, preservatives, pH adjusters, and the like. P.

In one embodiment, the cleaning composition contains from about 0.1 to about 10, preferably from about 0.25 to about 5% of the mass. CAC. In another embodiment, the cleansing composition contains from about 0.5 to about 2.5% of the mass. CAC. In an additional embodiment, the cleansing composition contains from about 1 to about 2.5% of the mass. CAC.

In one embodiment, the cleaning composition contains from about 0.1 to about 5, preferably from about 0.1 to about 2.5% of the mass. GMP. In another embodiment, the cleansing composition contains from about 0.5 to about 2.5% of the mass. GMP. In an additional embodiment, the cleansing composition contains from about 1 to about 2.5% of the mass. GMP.

In another embodiment, the cleansing composition is NEUTROGENA® Ultra-Mild Daily Cleanser available from Johnson & Johnson Consumer Inc.

The composition remaining on the skin contains at least one retinoid. As used herein, the term "retinoid" means a compound structurally similar to vitamin A, which is characterized by this structure:

,

,

where R represents a functional group such as CH ₂ OH (retinol), CHO (retinal), CO ₂ H (retinoic acid), CH ₂ OCOCH ₃ (retinyl acetate). Retinoids include other esters such as retinyl palmitate, amine derivatives, and the like. In one embodiment, the retinoid is selected from retinol, retinal, retinoic acid, retinyl acetate, and retinyl palmitate. In a preferred embodiment, the retinoid is retinol.

The skin-remaining composition may also optionally contain additional ingredients commonly used in skin-remaining compositions. You can also include a wide range of additional fat-soluble substances and/or water-soluble substances conventionally used in compositions for skin and hair care, in concentrations established in this field. For example, surfactants or emulsifiers, perlescent agents or opacifiers, thickeners, emollients, conditioners, humectants, chelating agents, scrubs, and additives that enhance the appearance, feel, or aroma of the cleansing composition, such as colors, fragrances, preservatives, may be included. , pH regulators, etc.

In one embodiment, the composition remaining on the skin comprises at least one polar emollient having a relative polarity index to retinoid of from about 0.5 to about 2, and at least one non-polar emollient having a relative polarity index to retinoid of from about 7 to about 10 wherein the weight ratio of said polar softener to said non-polar softener is from about 95:5 to about 40:60. For example, the non-polar softener may be selected from the group consisting of aromatic or linear esters, Guerbet ester, mineral oil, squalane, isohexadecane, squalene, liquid paraffin and mixtures thereof, in particular isohexadecane. The polar softener may be selected from the group consisting of propylene glycol stearyl ether, propylene glycol isostearate and mixtures thereof, in particular propylene glycol stearyl ether.

In another embodiment, the composition remaining on the skin contains an oil-in-water emulsion containing: (i) from about 0.05 to about 0.5% of the mass. retinol; (ii) propylene glycol stearyl ether; and (iii) isohexadecane, wherein the weight ratio of propylene glycol stearyl ether and isohexadecane is from about 75:25 to about 50:50 and the composition does not contain any additional active agents other than retinol.

In one embodiment, the composition remaining on the skin contains from about 0.001 to about 5% of the mass. retinoid. In one embodiment, the composition remaining on the skin contains from about 0.04 to about 2% of the mass. retinoid. In one embodiment, the composition remaining on the skin contains from about 0.04 to about 0.15% of the mass. retinoid.

In another embodiment, the composition remaining on the skin is NEUTROGENA® Rapid Wrinkle Repair® available from Johnson & Johnson Consumer Inc.

Optional Ingredients, Additional Compositions and Product Forms

Any one or both of the cleansing composition and the skin-retaining composition may contain other cosmetically acceptable excipients and/or active agents.

In addition, the present methods, regimens, and kits may optionally be implemented using a cleansing composition and a skin-remaining composition with one or more additional compositions, such as moisturizers, sunscreens, and the like.

Other cosmetically acceptable active agents for use in a cleansing composition, a skin-retention composition or an additional composition include, for example, acne treatment agents, gloss control agents, antimicrobial agents, anti-inflammatory agents, antifungal agents, antiparasitic agents, topical analgesics, sunscreens, photoprotectors, antioxidants, keratolytic agents, surfactants, humectants, nutrients, vitamins, energy boosting agents, antiperspirant agents, astringents, deodorants, thickening agents, anti-corn agents, hair and/or skin conditioning agents, and other glycosaminoglycans such as hyaluronic acid.

The amount of cosmetically active agent may be in the range from about 0.001% to about 20% of the mass. compositions, for example from about 0.005% to about 10% of the mass. compositions, for example from about 0.01% to about 5% of the mass. compositions.

The cosmetically acceptable active agent may be selected from, for example, hydroxy acid, benzoyl peroxide, D-panthenol, carotenoids, ceramides, polyunsaturated fatty acids, essential fatty acids, enzymes such as laccase, enzyme inhibitors, minerals, hormones such as estrogens, steroids, such as hydrocortisone, 2-dimethylaminoethanol, copper salts such as copper chloride, peptides such as argireline, Syn-ake and copper-containing peptides, coenzyme Q10, amino acids such as proline, vitamins, lactobionic acid, acetyl coenzyme A, niacin, riboflavin, thiamine, ribose, electron carriers such as NADH and FADH2, natural extracts such as aloe vera, feverfew, oats, dill, blackberry, paulownia tomentum, Picia anomala and chicory, resorcinols such as 4-hexylresorcinol, curcuminoids, sugar amines such as N-acetylglucosamines, and derivatives and mixtures thereof.

Examples of vitamins include, without limitation, vitamin A, B vitamins such as vitamin B3, vitamin B5 and vitamin B12, vitamin C, vitamin K, and various forms of vitamin E such as alpha, beta, gamma, or delta tocopherols. or their mixtures, and their derivatives.

Examples of hydroxy acids include, without limitation, glycolic acid, lactic acid, malic acid, salicylic acid, citric acid, and tartaric acid.

Examples of antioxidants include, without limitation, water-soluble antioxidants such as sulfhydryl compositions and their derivatives (e.g., sodium metabisulphite and N-acetylcysteine), lipoic acid and dihydrolipoic acid, resveratrol, lactoferrin, and ascorbic acid and ascorbic acid derivatives (e.g., ascorbyl palmitate). and ascorbyl polypeptide). Fat-soluble antioxidants suitable for use in the compositions of the present invention include butylated hydroxytoluene, retinoids (eg, retinol and retinyl palmitate), tocopherols (eg, tocopherol acetate), tocotrienols, and ubiquinone. Natural extracts containing antioxidants suitable for use in the compositions of the present invention include, without limitation, extracts containing flavonoids and isoflavonoids, as well as their derivatives (for example, genistein and diadzein), extracts containing resveratrol, and the like. Examples of such natural extracts include extracts of grape seed, green tea, pine bark and propolis.

The compositions may further include cosmetically acceptable topical carriers. The media can be from about 50% to about 99.99% of the mass. compositions (eg, from about 80% to about 99% by weight of the composition). In a preferred embodiment of the invention, the cosmetically acceptable topical carrier comprises water.

The compositions may be in the form of a variety of product types which include, but are not limited to, lotions, creams, gels, sticks, aerosols, ointments, cleansing liquids and sticks, shampoos and hair conditioners, hair fixatives, pastes, foams, powders, mousses, shaving creams, wipes, patches, hydrogels, film-forming products, face and skin masks, films and decorative cosmetics such as makeup bases, and mascaras and brows. Products of these types may contain a variety of cosmetically acceptable topical vehicles, including, without limitation, solutions, suspensions, emulsions such as microemulsions and nanoemulsions, gels, solids, and liposomes. The following are non-limiting examples of such carriers. Other carriers may be incorporated into the formulations by those skilled in the art.

The compositions may be prepared as solutions. Solutions typically include an aqueous or organic solvent (eg, 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, polypropylene glycol, glycerol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol, and mixtures thereof.

The compositions may be prepared as a solution containing a softener. Such compositions preferably contain from about 2% to about 50% softener(s). As used herein, the term "emollients" refers to substances used to prevent or eliminate dryness, for example by preventing transepidermal water loss from the skin. Examples of emollients include, without limitation, those listed in the International Cosmetic Ingredient Dictionary and Handbook, eds. Pepe, Wenninger and McEwen, pp. 2930-36 (The Cosmetic, Toiletry, and Fragrance Assoc., Washington, DC, 9th Edition, 2002) (hereinafter ICI Handbook). Examples of particularly suitable softeners include vegetable oils, mineral oils, fatty acid esters, and the like.

A lotion can be made from such a solution. Lotions typically contain from about 1% to about 20% (for example, from about 5% to about 10%) softener(s) and from about 50% to about 90% (for example, from about 60% to about 80 %) water.

Another type of product that can be prepared from a solution is a cream. Typically, a cream contains about 5% to about 50% (e.g., about 10% to about 20%) emollient(s) and about 45% to about 85% (e.g., about 50% to about 75% ) water.

The composition may alternatively be anhydrous or may be an ointment containing no water but containing organic and/or silicone solvents, oils, lipids and waxes. The ointment may contain a simple base of animal or vegetable oils or semi-solid hydrocarbons. The ointment may contain from about 2% to about 10% emollient(s) and from about 0.1% to about 2% thickener(s). Examples of thickeners include, without limitation, those listed in ICI Handbook pp. 2979-84.

The compositions may be formulated as an emulsion. If the topical carrier is an emulsion, then about 1% to about 10% (eg, about 2% to about 5%) of the topical carrier is the emulsifier(s). Emulsifiers can be non-ionic, anionic or cationic. Examples of emulsifiers include, without limitation, those listed in ICI Handbook pp. 2962-71.

Lotions and creams can be prepared as emulsions. Typically, such lotions contain from 0.5% to about 5% emulsifier(s). Such creams typically contain about 1% to about 20% (eg, about 5% to about 10%) emollient(s); 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).

Single phase emulsion based oil-in-water and water-in-oil skin care formulations, such as lotions and creams, are well known in the cosmetic field and can be used in the claimed invention. Compositions of the type "water-in-oil-in-water" or "oil-in-water-in-oil" based on a multi-phase emulsion are also used in the claimed invention. As such, such single or multi-phase emulsions contain water, softeners and emulsifiers as main ingredients.

The compositions may also be formulated as gels (eg, an aqueous, alcoholic, hydroalcoholic, or oily gel using a suitable gelling agent(s)). Suitable gelling agents for aqueous and/or alcoholic gels include, without limitation, natural gums, acrylic acid, and cellulose-derived acrylate polymers and copolymers (eg, hydroxymethylcellulose and hydroxypropylcellulose). Suitable gelling agents for oils (such as mineral oil) include, without limitation, hydrogenated butylene/ethylene/styrene copolymer and hydrogenated ethylene/propylene/styrene copolymer. In such gels, the content of these gelling agents, as a rule, is from about 0.1% to 5% of the mass.

The compositions may also be incorporated into solid formulations (eg wax sticks, sticks or powders). They can be applied to substrates such as woven or nonwoven fabrics, wipes, patches, masks, garments, and the like.

Retinoid activity

In accordance with the invention, pre-treatment of the skin with a cleansing composition containing LIPCA provides an increase in the activity of the retinoid after its topical application.

In one embodiment, the retinoid is retinol, and such pretreatment provides an increase in the bioavailability of retinol of at least about 150%, preferably at least about 180%, as measured by a change in the expression of the cellular retinoic acid binding protein type II (CRABPII) gene. ) compared to pre-treatment with retinol alone. The change in expression of the cellular retinoic acid binding protein type II gene (CRABPII) is measured by the CRABPII EXPRESSION TEST described in Example 1.

The following examples further illustrate the claimed invention.

Example 1

The activity of a retinol-containing product remaining on the skin (NEUTROGENA® Rapid Wrinkle Repair® (RWR)) was tested when it was used together in a regimen with various mild cleansers. Retinol activity was assessed using the in vitro CRABPII EXPRESSION TEST for expression of the cellular retinoic acid binding protein type II (CRABPII) gene, as described below.

Ex vivo skin explants with a diameter of one centimeter were obtained from skin samples taken by abdominal biopsy. Skin explants were maintained in KGM gold™ culture medium supplemented with amphotericin B, 0.125 μg/ml at 37° C., in a saturated atmosphere for a 48-hour test period. The explants were placed in a conventional assay plate, epidermal surface up, in sufficient culture medium to nearly but not completely submerge the sample (i.e., the epidermal surface protruded above the top surface of the medium). The mild cleanser under test was applied to the epidermal surface above the culture medium for 4 hours, followed by phosphate-buffered saline (PBS) washing and RWR application. After 48 hours, using conventional techniques known to those skilled in the art, explants were removed, epidermal mRNA was extracted from them, and CRABPII gene expression was measured by quantitative real-time PCR (qPCR-RT) using an acceptable oligonucleotide sequence.

The mild cleansers tested are described in Tables 1 and 2 below. The results are presented as fold changes from the corresponding values for the untreated control.

Table 1

Treatment The fold change relative to the value for the untreated sample (expression of the CRABPII gene) Standard deviation No processing one 0.15 Cleansing composition A ¹ 0.85 0.05 Comparative cleansing composition B ² 0.74 0.23 RWR 3.1 0.79 Cleansing composition A+RWR 5.8 0.71 Comparative cleansing composition B+RWR 2.6 0.23

¹ NEUTROGENA® Ultra-Mild Daily Cleanser, available from Johnson & Johnson Consumer Inc., containing: water, glycerin, cocamidopropyl betaine, potassium acrylate copolymer, lauryl glucoside, PEG-120 methyl dioleate, disodium lauroamphodiacetate, sodium cocoyl sarcosinate, ethylhexylglycerin , caprylyl, potassium sorbate, fragrance.

²OLAY® Sensitive Skin Foam Cleanser, available from Procter & Gamble, containing: Water, Glycerin, Sodium Myristoyl Sarcosinate, PEG-120 Methyl Glucose Dioleate, Sodium Lauroamphoacetate, Aloe Vera Leaf Juice, Polyquaternium-10, PEG-150 Pentaerythrityl Tetrastearate, Glycol Distearate, Sodium Laureth Sulfate, Cocamide Monoethanolamine, Laureth-10, DiSodium Lauroamphodiacetate, Sodium Trideceth Sulfate, citric acid, disodium EDTA, phenoxyethanol, DMDM hydantoin.

table 2

Treatment The fold change relative to the value for the untreated sample (expression of the CRABPII gene) Standard deviation No processing one 0.18 RWR 3.7 1.36 Cleansing composition A ¹ +RWR 7.2 2.9 Comparative cleansing composition C ² +RWR 3.2 1.6 Comparative cleansing composition D ³ +RWR 4.3 1.3

¹ NEUTROGENA® Ultra-Mild Daily Cleanser, available from Johnson & Johnson Consumer Inc., containing: water, glycerin, cocamidopropyl betaine, potassium acrylate copolymer, lauryl glucoside, PEG-120 methyl dioleate, disodium lauroamphodiacetate, sodium cocoyl sarcosinate, ethylhexylglycerin , caprylyl, potassium sorbate, fragrance.

² CETAPHIL Gentle Skin Cleanser, available from Galderma, containing: Water, Cetyl Alcohol, Propylene Glycol, Sodium Lauryl Sulfate, Stearyl Alcohol, Methylparaben, Propylparaben, Butylparaben.

³ CETAPHIL Daily Cleansing Foam, available from Galderma, containing: water (purified), sodium lauroyl sarcosinate, acrylates/steareth-20-methacrylate crosspolymer, glycerin, PEG-200 hydrogenated glyceryl palmate, sodium laureth sulfate, butylene glycol, PEG-7 glyceryl cocoate, phenoxyethanol, masking fragrance (fragrance), panthenol, PEG-60 hydrogenated castor oil, disodium EDTA, methylparaben.

These results show that tissue pre-treatment with a cleansing composition containing LIPCA according to the invention prior to application of a retinol-containing product resulted in a subsequent increase in retinol biological activity, compared with application of the retinol-containing product alone, and compared with pre-treatment with cleansing compositions that did not containing LIPCA.

Example 2

The in vitro mildness (as measured by IL-1α levels) of the various treatments was determined as described below.

Epidermal equivalents (EPI 200 HCF), stratified and differentiated epidermis composed of normal human epidermal keratinocytes, obtained from MatTek (Ashland, Massachusetts, USA). After receiving the epidermal equivalents were incubated for 24 hours at 37°C in maintenance medium without hydrocortisone. Equivalents were treated topically with the products listed in Table 3 (volume 6 μl) for 1 hour, subsequently washed twice with phosphate-buffered saline (PBS). The equivalents were subsequently incubated for 24 hours at 37°C in maintenance medium, then the supernatants were analyzed for the release of the cytokine IL-1α using commercially available kits (Millipore Corp., Billerica, Massachusetts, USA).

Table 3

Treatment Mean IL-1α release (pg/mL) No processing 77.9 Cleansing composition A ¹ 243.9 Comparative cleansing composition B ² 888.3 Comparative cleansing composition C ³ 906.3 Comparative cleansing composition D ⁴ 91.3

¹ NEUTROGENA® Ultra-Mild Daily Cleanser, available from Johnson & Johnson Consumer Inc., containing: water, glycerin, cocamidopropyl betaine, potassium acrylate copolymer, lauryl glucoside, PEG-120 methyl dioleate, disodium lauroamphodiacetate, sodium cocoyl sarcosinate, ethylhexylglycerin , caprylyl, potassium sorbate, fragrance.

²OLAY® Sensitive Skin Foam Cleanser, available from Procter & Gamble, containing: Water, Glycerin, Sodium Myristoyl Sarcosinate, PEG-120 Methyl Glucose Dioleate, Sodium Lauroamphoacetate, Aloe Vera Leaf Juice, Polyquaternium-10, PEG-150 Pentaerythrityl Tetrastearate, Glycol Distearate, Sodium Laureth Sulfate, Cocamide Monoethanolamine, Laureth-10, DiSodium Lauroamphodiacetate, Sodium Trideceth Sulfate, citric acid, disodium EDTA, phenoxyethanol, DMDM hydantoin.

³ CETAPHIL Daily Cleansing Foam, available from Galderma, containing: water (purified), sodium lauroyl sarcosinate, cross-linked acrylates/steareth-20-methacrylate copolymer, glycerin, PEG-200 hydrogenated glyceryl palmate, sodium laureth sulfate, butylene glycol, PEG- 7 glyceryl cocoate, phenoxyethanol, masking fragrance (fragrance), panthenol, PEG-60 hydrogenated castor oil, disodium EDTA, methyl paraben.

⁴ CETAPHIL Gentle Skin Cleanser, available from Galderma, containing: Water, Cetyl Alcohol, Propylene Glycol, Sodium Lauryl Sulfate, Stearyl Alcohol, Methylparaben, Propylparaben, Butylparaben.

These results show that Cleansing Composition A and Comparative Cleansing Composition D provide low levels of IL-1α release, indicative of mild action. However, as shown in Example 1, only Cleansing Composition A containing LIPCA according to the invention provides both mildness and increased retinol activity.

Claims (5)

1. The method of skin treatment, including sequentially: (a) cleansing skin requiring the elimination of signs of skin aging, acne or rosacea, using a cleansing composition containing a low molecular weight hydrophobically modified polymer, which is a copolymer of potassium acrylates; and (b) topical application to the skin of a retinoid-containing composition remaining on the skin. 2. The method of claim 1 wherein the retinoid is selected from the group consisting of retinol, retinal, retinoic acid, retinyl acetate and retinyl palmitate. 3. The method of claim 1 wherein the retinoid is retinol.