CN1347309A - Skin care compositions contg. combination of skin care actives - Google Patents

Abstract

The present invention relates to skin care compositions comprising combinations of skin care actives, and methods of using the compositions to regulate skin condition. The composition comprises a safe and effective amount of farnesol; a safe and effective amount of bisabolol; a safe and effective amount of at least one additional skin care active; and a dermatologically acceptable carrier.

Description

Skin care composition comprising combination of skin care actives

Technical field

The present invention relates to topical compositions comprising skin care actives, especially farnesol, bisabolol and at least one additional skin care active. The composition is useful for regulating the condition of the skin, in particular regulating visible and/or tactile skin discontinuities associated with skin aging. Preferred compositions also contain phytantriol.

Cross Reference

This application is a continuation-in-part of a co-pending application (application number not yet received, P&G Docket No. 7525M, filed April 4, 2000), which in turn claimed provisional application 60/129,975 pursuant to 35 USC § 119(e) (filed 19 April 1999) priority. This application is also a continuation-in-part of US Application Serial No. 09/441,303, filed November 16,1999. Additionally, this application claims priority under 35 USC §119(e) to provisional application 60/175,315, filed January 10,2000.

Cross Reference

This application is a continuation-in-part of US Application Serial No. 09/441,303, filed November 16,1999. This application is a continuation-in-part of a co-pending application (application number not yet received, P&G Docket No. 7525M, filed April 4, 2000), which in turn claimed provisional application 60/129,975 pursuant to 35 USC § 119(e) (filed 19 April 1999) priority. Additionally, this application claims priority under 35 USC §119(e) to provisional application 60/175,315, filed January 10,2000.

Background of the invention

Many personal care products available to consumers today are primarily intended to improve skin health and/or physical appearance. Among these skin care products, many are aimed at delaying, reducing or even eliminating skin wrinkles and other tissue lesions generally associated with skin aging or environmental aggression to human skin. Various compounds have been described in the art for regulating skin condition, including regulating fine lines, wrinkles, and other uneven or rough skin surface textures associated with aging or photodamaged skin.

The skin is attacked by many extrinsic and intrinsic factors. Extrinsic factors include ultraviolet radiation (such as from exposure to sunlight), environmental pollution, wind, heat, low humidity, harsh surfactants, abrasives, etc. Intrinsic factors include chronic aging and other biochemical changes within the skin. Both these extrinsic and intrinsic factors contribute to the visible signs of skin aging and environmental aggression, such as wrinkles and other forms of roughness (including enlarged pores, scaling, and fine lines), and other permanent signs associated with skin aging and aggression Variety. For many people, wrinkled skin is a sign of lost youth. Therefore, eliminating wrinkles has become a hot topic in a youth-conscious society. Treatments range from cosmetic creams and moisturizers to various forms of topicals.

Extrinsic and intrinsic factors can lead to thinning and common degeneration of the skin. For example, as skin naturally ages, the cells and blood vessels that supply it decrease. Furthermore, the dermal-epidermal junction is flattened, making this junction less mechanically resistant. See, eg, "Skin Aging: Chronic Aging and Photoaging" by Oikarinen, Photodermatol Photoimmunol Photomed., Vol. 7, pp. 3-4, 1990, which is incorporated herein by reference.

A variety of skin care actives are known in the art for improving the health and/or appearance of the skin. For example, salicylic acid and benzoyl peroxide are used in skin care compositions for treating acne. Retinoids are another example of skin care actives in skin care compositions used to reduce the signs of skin aging. While formulating skin care compositions containing such actives provides skin care benefits, there are a number of difficulties with formulating such compositions. For example, typical retinoid compositions must be prepared under specific conditions, such as in an inert environment, and may also exhibit non-optimal long-term stability, such as discoloration. Compositions containing certain skin care actives may produce skin irritation such as stinging, burning and redness.

Based on the above analysis, there is a continuing need to formulate skin care compositions that improve skin health and/or appearance, such as aesthetically appealing, stable, effective treatments for wrinkles, fine lines, pores, unsightly skin tone (such as pan- redness, sallow complexion, and other forms of poor skin surface texture).

Surprisingly, it has now been found that compositions comprising a multi-active system, in particular a combination of farnesol and bisabolol and at least one additional skin care active, provide skin condition regulating benefits not previously recognized in the art . For example, topical application of farnesol in combination with bisabolol and at least one additional skin care active can synergistically regulate (prophylactically and/or therapeutically) visible and/or tactile Discontinuities in skin, including fine lines, wrinkles, large pores, roughness, dryness, and other discontinuities in skin texture, such as reducing or erasing visible fine lines, wrinkles, and other forms of aging or photodamaged skin Associated uneven or rough surface textures.

The prior art cannot provide all the advantages and effects of the present invention.

Invention Summary

The present invention relates to a composition comprising a safe and effective amount of farnesol; a safe and effective amount of bisabolol; a safe and effective amount of at least one additional skin care active; and a dermatologically acceptable carrier.

The present invention also relates to the use of such compositions to regulate the condition of mammalian skin. The method generally includes the step of topically applying a safe and effective amount of the composition to the skin of the mammal to be treated.

A preferred embodiment comprises phytantriol.

These and other features, aspects, and advantages of the present invention will be readily apparent to those skilled in the art after reading the present disclosure.

Detailed description of the invention

While the contents of the specification are concluded in the claims which particularly point out and distinctly claim the invention, it is believed that the invention will be better understood from the following description.

All percentages and ratios herein are by weight of the total composition and all measurements made are at 25°C unless otherwise indicated.

The compositions of the present invention may comprise, consist of, or consist essentially of the ingredients of the present invention as well as other ingredients described herein. Here, "consisting essentially of these ingredients" means that the composition or component may contain other ingredients, as long as the other ingredients do not significantly change the basic and novel characteristics of the claimed composition or method.

The publications cited herein are hereby incorporated by reference in their entirety

The term "keratinous tissue" as used herein refers to the outermost protective covering of mammals (such as humans, dogs, cats, etc.) containing keratin, which includes, but is not limited to, skin, lips, hair, toes, fingers , epidermis, hooves and other parts.

Here "topical application" refers to applying or spreading the composition of the present invention on the surface of keratinous tissue.

The term "dermatologically acceptable" herein means that the composition or component is suitable for contact with human keratinous tissue without undue toxicity, incompatibility, instability, allergic reaction, and the like.

Herein, the term "safe and effective amount" refers to the amount of such compound or composition, which can obviously produce beneficial effect, preferably beneficial keratinous tissue appearance or skin effect, independently or in combination, including the various benefits mentioned herein, but can To avoid serious side effects, if a reasonable benefit-harm ratio is produced, the dosage is within the reasonable judgment range of the technician.

The term "sagging" as used herein refers to laxity, looseness and the like of the skin due to loss, damage, alteration and/or abnormality of the elastin of the skin.

The terms "smooth" and "softening" herein refer to modifying the surface of keratinous tissue to improve its tactile effect.

"Signs of skin aging" include, but are not limited to, all externally visible and/or tactile manifestations as well as any other macroscopic or microscopic effects attributable to skin aging. These signals can be caused by intrinsic and extrinsic factors, such as chronic aging and/or environmental aggression. These signals can arise from processes including, but not limited to: development of textural discontinuities such as wrinkles and rough deep lines, skin lines, fissures, bumps, coarse pores (e.g. associated with accessory structures such as sweat glands, sebaceous glands, and hair follicles) ), or rough or uneven skin, loss of skin elasticity (loss and/or inactivation of functional skin elastin), sagging (including bags under the eyes and lower cheek puffiness), loss of skin firmness, loss of skin toughness, skin rebound due to deformation Loss, discoloration (including the under-eye area), blemishes, sallowness, dark areas such as age spots, freckles, horniness, abnormal coloration, hyperkeratinization, elastosis, collagen breakdown, and others in the stratum corneum, epidermis, dermis , skin vasculature (eg, telangiectasias and spider vessels), and subcutaneous tissue, especially in areas adjacent to the skin, are permanently altered.

The present invention is useful for therapeutically modulating visible and/or tactile discontinuities in mammalian skin, including discontinuities in skin texture and skin tone. For example, a decrease in the apparent diameter of the pore, the apparent height of the tissue immediately adjacent to the pore approaching that of interadnexal skin, more even skin tone, and/or the length of fine lines and/or wrinkles , depth and/or other dimension reduction.

The compositions of the invention are also suitable for regulating the condition of the skin and especially for regulating the condition of keratinous tissue. Regulating the condition of the skin, ie the condition of the skin of mammals, especially humans, is often desired because various external and/or internal factors contribute to these conditions. Examples include environmental damage, radiation (including ultraviolet radiation), chronic aging, menopausal conditions (eg, postmenopausal skin changes), stress, disease, and the like. For example, "regulating skin condition" includes prophylactic and/or therapeutic regulation of skin condition and may involve one or more of the following benefits: skin densification (i.e. structuring of the epidermis and/or dermis and/or subcutaneous (i.e. subcutaneous fat) or muscle) layer, and when applicable toe/nail and hair shaft cuticle) to reduce skin atrophy, increase tangles at the dermal junction (also known as the ridge network), and prevent loss of skin elasticity (functional skin elasticity Loss, damage, and/or inactivation of proteins) such as elastosis, sagging, loss of skin elasticity due to deformation; discoloration of non-melanotic skin such as dark circles, spots (eg, uneven reddening due to rosacea) (hereinafter referred to as "erythema"), sallow (pale), discoloration due to capillaries or their dilation.

As used herein, prophylactically regulating skin condition includes delaying, minimizing and/or preventing visible and/or tactile discontinuities in the skin (eg, macroscopically or palpably irregularities in skin texture.

As used herein, therapeutically regulating skin condition includes improving, eg reducing, minimizing and/or eliminating skin discontinuities.

Compositions of the invention may also be used to improve appearance and/or feel. For example, the composition of the present invention regulates the appearance of the skin by providing an immediate improvement in the appearance of the skin upon application to the skin. In general, compositions of the present invention which also comprise particulate material are most effective in providing immediate visible improvement.

The compositions of the present invention provide additional benefits including stability, absence of significant (consumer unacceptable) skin irritation and good aesthetics.

The compositions of the present invention are stable. The ingredients used herein including farnesol, bisabolol and other skin care actives are stable in the composition and compatible with the other ingredients. Thus, compositions comprising farnesol, bisabolol and at least one additional skin care active provide additional and/or synergistic skin benefits. In addition, the resulting skin care compositions have good product stability and a reasonably long shelf life.

Compositions comprising farnesol, bisabolol and at least one additional skin care active have a favorable cosmetic effect. Examples of good aesthetics include compositions such as delicate creams and lotions that are (i) non-heavy and non-greasy, (ii) have a smooth and silky feel on the skin, (iii) spread easily open, and/or (iv) fast absorbed. Other examples of good aesthetics include compositions that have a consumer-acceptable appearance (ie, no unpleasant odor or discoloration present) and provide a good skin feel.

The compositions of the present invention comprise farnesol, bisabolol, at least one additional skin care active, and a dermatologically acceptable carrier. The composition also includes various optional components.

The composition of the present invention is described in detail below.

I. Farnesol

The topical compositions of the present invention comprise a safe and effective amount of farnesol. Farnesol is a naturally occurring substance that is thought to serve as a precursor and/or intermediate in the biosynthesis of squalene and sterols, especially cholesterol. Farnesol is also involved in protein modification and regulation (eg farnesylation of proteins) and there are nuclear receptors responsive to farnesol.

Chemically farnesol is [2E,6E]-3,7,11-trimethyl-2,6,10-dodecatrien-1-ol, where farnesol includes isomers and tautomers body. Farnesol is available as farnesol (mixture of isomers, available from Dragoco, 10 Gordon Drive, Totowa, New Jersey) and trans-trans-farnesol (available from Sigma Chemical Company, P.O. Box 14508, St Louis, Missouri) is commercially available.

The compositions of the present invention preferably comprise from about 0.001% to about 50% by weight of the composition, more preferably from about 0.01% to about 20%, more preferably from about 0.1% to about 15%, more preferably from about 0.1% to about 10%, more preferably about 0.5% to about 5%, more preferably about 1% to about 5% farnesol.

II. Bisabolol

它是春黄菊提取物的主要活性组分。红没药醇可以是合成的(d，1-α-异构体或(+/-)-α-异构体)或天然的((-)-α-异构体)，并可以基本上纯的化合物或这些化合物的混合物的形式使用(例如从天然源如春黄菊提取的物质)。α形的红没药醇(α-红没药醇)在许多化妆品中用作皮肤调理或舒适剂。这里的“红没药醇”包括春黄菊的提取物和油，及其任何异构体和互变体。适宜的红没药醇化合物有购自Dragoco(Totowa，New Jersey)的天然物质，产品名称为天然α-红没药醇，或是购自Fluka(Milwaukee，Wisconsin)的合成物质，产品名称为α-红没药醇。The topical compositions of the present invention comprise bisabolol in a safe and effective amount. It is a naturally occurring unsaturated monocyclic terpene alcohol with the following structure:

It is the main active component of chamomile extract. Bisabolol can be synthetic (d,1-α-isomer or (+/-)-α-isomer) or natural ((-)-α-isomer) and can be essentially The compounds are used in the form of pure compounds or mixtures of these compounds (eg, substances extracted from natural sources such as chamomile). The alpha form of bisabolol (α-bisabolol) is used in many cosmetic products as a skin conditioning or comforting agent. "Bisabolol" here includes extracts and oils of chamomile, and any isomers and tautomers thereof. Suitable bisabolol compounds are the natural material available from Dragoco (Totowa, New Jersey) under the product name natural α-bisabolol or the synthetic material available from Fluka (Milwaukee, Wisconsin) under the product name α-bisabolol. - Bisabolol.

In the composition of the present invention, the composition preferably comprises from about 0.001% to about 50% by weight of the composition, more preferably from about 0.01% to about 20%, more preferably from about 0.01% to about 15%, more preferably from about 0.1% to About 10%, more preferably about 0.1% to about 5% bisabolol.

III. Additional skin care actives

The compositions of the present invention comprise at least one additional skin care active. The compositions of the present invention may also contain a variety of other skin care actives.

In a preferred embodiment, when the composition is to come into contact with human keratinous tissue, these additional skin care actives should be suitable for keratinous tissue, that is, when they are introduced into the composition, they are suitable for contacting human keratinous tissue without reasonable medical Undue toxicity, incompatibility, instability, denaturation, etc. within the scope of judgment. The CTFA Cosmetic Ingredient Handbook, 2nd Edition (1992) describes a wide variety of non-limiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry, which are suitable for use in the compositions of the present invention. Examples of these classes of ingredients include: abrasives, absorbents, aesthetic components such as fragrances, pigments, colorants, essential oils, skin sensates, astringents, etc. (e.g. clove oil, menthol, camphor, , eugenol, menthyl lactate, witch hazel distillate), anti-acne agents, anti-caking agents, anti-foaming agents, anti-microbial agents (such as iodopropyl butyl carbamate), antioxidants, viscose Binders, biological additives, buffers, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, pharmaceutical astringents, external analgesics, film-forming agents such as Film-forming and substantive polymers (such as eicosene and vinylpyrrolidone copolymers), opacifiers, pH regulators, propellants, reducing agents, sequestering agents, skin whitening and lightening agents ( such as hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosamine), skin conditioning agents (such as humectants, including diverse and non-occlusive ingredients), skin comforting and/or healing agents (such as panthenol and its derivatives such as ethyl panthenol), aloe, pantothenic acid and its derivatives, allantoin, bisabolol, and dipotassium glycyrrhizinate), skin treatment agents, thickeners, and vitamins and their derivatives .

In any embodiment of the invention, however, the actives used herein can be classified by their envisaged mode of action or by the effect they provide. However, it is understood that the actives herein may in some instances provide more than one effect or operate via more than one mode of action. This classification is therefore for convenience and does not limit the active to a specific indicated effect.

Phytantriol

The topical compositions of the present invention may contain a safe and effective amount of phytantriol. Phytantriol is the common name for the compound 3,7,11,15-tetramethylhexadecane-1,2,3-triol. Phytantriol is commercially available from BASF (1609 Biddle Avenue, Whyandotte, MI). For example, phytantriol is used as a capillary/erythema repair agent, dark circle/puffy eye bubble repair agent, sallow complexion repair agent, sagging repair agent, anti-itch agent, skin tightening agent, pore reducer, oil/shine reducer agent, post-inflammatory hyperpigmentation repair agent, wound treatment agent, anti-cellulite agent (anti-cellulite agent), and regulates skin texture, including wrinkles and fine lines.

When included in the compositions of the present invention, phytantriol preferably comprises from about 0.001% to about 50% by weight of the composition, more preferably from about 0.01% to about 20%, more preferably from about 0.1% to about 15%, and more preferably Preferably from about 0.2% to about 10%, more preferably from about 0.5% to about 10%, still more preferably from about 1% to about 5%. Desquamation Actives

Safe and effective amounts of desquamation actives may be incorporated into the compositions of the present invention, more preferably from about 0.1% to about 10%, more preferably from about 0.2% to about 5%, by weight of the composition, and also preferably is about 0.5% to about 4%. The skin appearance benefits of the present invention are enhanced by desquamation actives. For example, desquamation actives help improve skin texture (eg, smoothness). One class of desquamation systems useful herein contains mercapto compounds and zwitterionic surfactants and is described in US 5681852 to Bissett (incorporated by reference). Another class of exfoliating systems suitable for use herein comprises salicylic acid and zwitterionic surfactants and is described in US 5652228 to Bisett (incorporated by reference). Zwitterionic surfactants such as those described in these applications are also useful as desquamation agents herein, cetyl betaine being especially preferred. anti-acne actives

The compositions of the present invention may contain a safe and effective amount of one or more anti-acne actives. Examples of suitable anti-acne actives are resorcinol, sulfur, salicylic acid, benzoyl peroxide, erythromycin, zinc, and the like. Examples of other suitable anti-acne actives are described in USP 5,607,980, issued March 4, 1997 to McAtee et al. Anti-Wrinkle Actives/Anti-Atrophy Actives

The compositions of the present invention may further comprise a safe and effective amount of one or more anti-wrinkle or anti-atrophy actives. Examples of such actives suitable here are sulfur-containing D and L amino acids and their derivatives and salts, especially N-acetyl derivatives, a preferred example of which is N-acetyl-L-cysteine; sulfur Alcohols, such as ethanethiol; hydroxy alcohols (such as alpha-hydroxy acids, such as lactic acid and glycolic acid, or beta-hydroxy acids, such as salicylic acid and its derivatives such as octanoyl derivatives), phytic acid, lipoic acid; lysophospholipids Acids, peeling agents (such as phenol, etc.), vitamin _B3 compounds, and retinoids, which enhance the benefits of the appearance of keratinous tissue of the present invention, especially in regulating keratinous tissue conditions such as skin conditions. a).Vitamin _B3 compound

The compositions of the present invention comprise a safe and effective amount of a vitamin _B3 compound. Vitamin _B3 compounds are especially useful for regulating skin situation. When it is present in the compositions of the present invention, the compositions preferably comprise from about 0.01% to about 50%, more preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 10%, and more preferably about 1% to about 5%, more preferably about 2% to about 5%, vitamin _B3 compound.

Here "vitamin _B3 compound" means a compound having the following formula:

wherein R is _-CONH2 (ie nicotinamide), -COOH (ie nicotinic acid) or _-CH2OH (ie nicotinic alcohol); derivatives thereof; and salts of any of the foregoing.

Exemplary derivatives of the aforementioned vitamin _B3 compounds include nicotinic acid esters, including nicotinic acid (such as tocopheryl nicotinate), non-vasodilatory esters of nicotinic acid amino acids, nicotinol esters of carboxylic acids, nicotinic acid N-oxide and Niacinamide N-oxide.

Examples of the aforementioned vitamin _B3 compounds are well known in the art and are available from various commercial sources such as Sigma Chemical Company (St. Louis, MO), ICN Biomedicals Inc. (Irvin, CA) and Aldrich Chemical Company (Milwaukee, CA). WI).

Vitamin _B3 compounds may be included as substantially pure material, or as extracts obtained by suitable physical and chemical isolation from natural sources such as plants. b) Retinoids

The compositions of the present invention comprise a retinoid. As used herein, "retinoids" include all natural and/or synthetic congeners of vitamin A or retinol-like compounds that possess the biological activity of vitamin A in the skin, as well as geometric isomers of these compounds and stereoisomers. Retinoids are preferably retinol, retinyl esters (such as C2-C22 alkyl esters of retinol, including retinyl palmitate, retinyl acetate, retinyl propionate), retinyl Aldehydes, and/or retinoic acid (including all-trans retinoic acid and/or 13-cis retinoic acid), more preferably retinoids other than retinoic acid. These compounds are well known in the art and are commercially available from various sources such as Sigma Chemical Company (St. Louis, MO), and Boerhinger Mannheim (Indianapolis, IN). Other retinoids employed herein are described in USP 4677120, issued June 30, 1987 to Parish et al; 4885311, issued December 5, 1989 to Parish et al; 5049584, issued September 17, 1991 to Purcell et al; , authorized June 23, 1992 to Purcell et al; and Reissue 34075, issued September 22, 1992 to Purcell et al. Other suitable retinoids are tocopheryl retinoate [(cis or trans) tocopheryl retinoate, adapalene {6-[3-(1-adamantyl)-4-methoxyphenyl]- 2-naphthoic acid} and tazarotene (ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate). Preferred retinoids are retinol, retinyl palmitate, retinyl acetate, retinyl propionate, retinal and combinations thereof.

Retinoids may be used as substantially pure material, or as extracts obtained by suitable physical and/or chemical isolation from natural (eg, plant) sources. Preferably the retinoid is substantially pure, more preferably essentially pure.

The composition of the present invention may preferably contain a safe and effective amount of retinoid, so that it is safe and effective for regulating skin condition, especially for regulating visible and/or tactile discontinuities of the skin, more preferably for regulating skin aging Signaling, again preferably, is safe and effective for visible and/or tactile skin texture discontinuities associated with skin aging. The compositions preferably contain from about 0.005% to about 2%, more preferably from 0.01% to about 2%, of a retinoid. Retinol is preferably used in an amount of about 0.01% to about 0.15%; retinol esters are preferably used in an amount of about 0.01% to about 2% (eg, about 1%); retinoic acid is preferably used in an amount of about 0.01% to about 0.25% ; tocopheryl retinoate, adapalene, and tazarotene are preferably used in amounts of about 0.01% to about 2%.

When the compositions of the present invention contain both retinoids and vitamin B3 compounds, the retinoids are preferably used in the amounts described above, and the vitamin _B3 compounds are preferably used in an amount of from about 0.1% to about 10%, more preferably from about 2% to about 5%. (c) Hydroxy acids

The compositions of the present invention also contain a safe and effective amount of a hydroxy acid. Preferred hydroxy acids for use in the present invention include salicylic acid and its derivatives. When present in the compositions of the present invention, salicylic acid is preferably used in an amount from about 0.01% to about 50%, more preferably from about 0.1% to about 20%, still more preferably from about 0.1% to about 10%, still more preferably from about 0.5% to About 5%, more preferably about 0.5% to about 2%. peptide

The compositions of the present invention may contain a safe and effective amount of peptides, including but not limited to di-, tri-, tetra- and penta-peptides and their derivatives. "Peptide" herein refers to naturally occurring as well as synthetic peptides. Naturally occurring and commercially available compositions containing peptides can also be used herein.

Tripeptides suitable for use herein include carnosine (beta-ala-his). Useful tripeptides herein include gly-his-lys, arg-lys-arg, his-gly-gly. Preferred tripeptides and derivatives thereof include palmitoyl-gly-his-lys, which can be commercially available Biopeptide CL® (100 ppm palmitoyl-gly-his-lys available from Sederma, France); Peptide CK (arg- lys-arg); Peptide CK+ (ac-arg-lys-arg-NH ₂ ); and copper derivatives of his-gly-gly (Iamin, available from Sigma, St. Louis, MO). Tetrapeptides suitable for use herein include Peptide E, arg-ser-arg-lys (SEQ ID NO: 1). Pentapeptides suitable for use herein include lys-thr-thr-lys-ser. A preferred commercially available pentapeptide derivative composition is Matrixyl(R), which contains 100 ppm of palmitoyl-lys-thr-thr-lys-ser (SEQ ID NO: 2, available from Sederma, France).

The peptide is preferably selected from palmitoyl-lys-thr-thr-lys-ser, palmitoyl-gly-his-lys, beta-ala-his, and derivatives and combinations thereof. More preferably the peptide is selected from palmitoyl-lys-thr-thr-lys-ser, palmitoyl-gly-his-lys, derivatives thereof and combinations thereof. Still more preferably, the peptide is selected from palmitoyl-lys-thr-thr-lys-ser and derivatives thereof.

When included in the compositions of the present invention, peptides are preferably present in an amount of from about 1× ^10-6 % to about 10%, more preferably from about 1× ^10-6 % to about 0.1%, and still more preferably from about 1×10-6% by weight of the composition. 10 ^-5 % to about 0.01%. In compositions wherein certain peptides are carnosine ^(R) , the compositions preferably contain from about 0.1% to about 5% by weight of the composition of such peptides. In other embodiments comprising a peptide-containing composition, Matrixy ^(R) and/or Biopeptide CL( ^R) , the composition preferably contains from about 0.1% to about 10% by weight of the composition of Matrixyl ^(R ) and/or Biopeptide CL ^(R) peptide-containing composition. Antioxidant/Free Radical Scavenger

The compositions of the present invention may contain a safe and effective amount of an antioxidant/radical scavenger. Antioxidants/radical scavengers are especially useful in protecting the skin from UV rays and other environmental factors that can cause increased scaling or changes in the texture of the stratum corneum.

Antioxidants/radical scavengers are included in the compositions of the present invention in safe and effective amounts, preferably from about 0.1% to about 10%, more preferably from about 1% to about 5%, of the composition.

Antioxidants/radical scavengers that can be used are, for example, ascorbic acid (vitamin C) and its salts, ascorbic acid esters of fatty acids, ascorbic acid derivatives (such as magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherols (vitamin E), tocopheryl sorbate, other esters of tocopherol, butylated hydroxybenzoic acid and its salts, 6-hydroxy-2,5,7,8-9 methylchroman-2- Carboxylic acids (commercially available under the name ^Trolox® , gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (such as N, N-diethylhydroxylamine, aminoguanidine), sulfhydryl compounds (such as glutathione) and dihydroxyfumaric acid and its salts, lycium pidolate, arginine pidolate, nordihydroguaiaretic acid, biological Flavonoids, curcumin, lysine, methionine, proline, superoxide dismutase, silymarin, tea extract, grape skin/seed extract, melanin and rosemary extract. Preferred The antioxidant/radical scavenger is selected from tocopheryl sorbate and other esters of tocopherol, more preferably tocopheryl sorbate. For example, authorized July 11, 1989 by Donald L. Bissett, Rodney D. Bush and Ranjit Chatterjee Tocopheryl sorbate for use in topical compositions and suitable for use in the present invention is described in USP No. 4,847,071. Chelating agents

The compositions of the present invention may contain a safe and effective amount of a chelating agent or chelating agent. As used herein, "chelating agent" or "chelating agent" means an active agent capable of removing metal ions from a system by forming complexes so that the metal ions cannot readily participate in or catalyze chemical reactions. The addition of chelating agents is particularly effective in preventing skin damage from UV rays and other environmental factors that can cause excessive scaling or changes in skin tissue.

The chelating agent is included in the compositions of the present invention in a safe and effective amount, preferably from about 0.1% to about 10%, more preferably from about 1% to about 5%, of the composition. Typical chelating agents useful herein are disclosed in USP 5487884, issued 1/30/96 to Bissett et al; International Application Publication 91/16035, published 10/31/95 to Bush et al; and International Application Publication 91 to Bush et al. /16034, open date 10/31/95. The chelating agent used in the composition of the present invention is preferably furildioxime, furil monoxime and derivatives thereof. flavonoids

Compositions of the present invention may optionally contain flavonoid compounds. Flavonoids are broadly disclosed in US5686082 and 5686367, which are incorporated herein by reference. Flavonoids suitable for use in the present invention are flavanones selected from unsubstituted flavanones, monosubstituted flavanones and mixtures thereof; chalcones selected from unsubstituted chalcones, monosubstituted, disubstituted and trisubstituted chalcones and mixtures thereof; flavones selected from unsubstituted flavones, monosubstituted and disubstituted flavones, and mixtures thereof; one or more isoflavones; coumarins selected from Unsubstituted coumarins, monosubstituted, and disubstituted coumarins, and mixtures thereof; chromones selected from unsubstituted chromones, monosubstituted, and disubstituted chromones, and mixtures thereof; One or more sputum; One or more chroman-4-ones; One or more chromanols (chromanol); Its isomers (such as cis/trans isomers); and mixtures thereof. The term "substituted" herein refers to flavonoids in which one or more hydrogen atoms have been independently substituted by hydroxyl, C1-C8 alkyl, C1-C4 alkoxy, O-glycoside, etc., and mixtures of these substituents. flavonoids.

Examples of suitable flavonoids include, but are not limited to, unsubstituted flavanones, monohydroxyflavanones (such as 2'-hydroxyflavanones, 6-hydroxyflavanones, 7-hydroxyflavanones, etc.), Oxyflavanone (such as 5-methoxyflavanone, 6-methoxyflavanone, 7-methoxyflavanone, 4'-methoxyflavanone, etc.), unsubstituted chalco Chalcone (especially unsubstituted trans-chalcone), monohydroxychalcone (such as 2'-hydroxychalcone, 4'-hydroxychalcone, etc.), dihydroxychalcone (such as 2', 4-Dihydroxychalcone, 2',4'-Dihydroxychalcone, 2,2'-Dihydroxychalcone, 2',3-Dihydroxychalcone, 2',5'-Dihydroxychalcone Chalcone, etc.), and trihydroxychalcone (such as 2', 3', 4'-trihydroxychalcone, 4,2', 4'-trihydroxychalcone, 2,2', 4' -trihydroxychalcone, etc.), unsubstituted flavones, 7,2'-dihydroxyflavones, 3',4'-dihydroxynaphthoflavones, 4'-hydroxyflavones, 5,6-benzoflavones, and 7 , 8-benzoflavone, unsubstituted isoflavone, daidzein (7,4'-dihydroxyisoflavone), 5,7-dihydroxy-4'-methoxyisoflavone, soybean isoflavone (soybean Extract mixture), unsubstituted coumarin, 4-hydroxycoumarin, 7-hydroxycoumarin, 6-hydroxy-4-methylcoumarin, unsubstituted chromone, 3-formylchromone, 3-formyl-6-isopropyl chromone, unsubstituted romansin, unsubstituted chroman-4-one, unsubstituted chroman-4-ol, and mixture.

Preferred here are unsubstituted flavanones, methoxyflavanones, unsubstituted chalcones, 2'-4 dihydroxychalcones, and mixtures thereof. More preferred are unsubstituted flavanones, unsubstituted chalcones (especially the trans isomer), and mixtures thereof.

They can be synthetic substances or extracts obtained from natural sources such as plants. Natural source materials may also be derivatized (eg, ester or ether derivatives prepared after extraction from natural sources). Flavonoid compounds useful herein are commercially available from a variety of sources, such as Indofine Chemical Company (Somerville, New Jersey), Steraloids Company (Wilton, New Hampshire), and Aldrich Chemical Company (Milwaukee, Wisconsin).

Mixtures of the above flavonoid compounds may also be used.

Preferred concentrations of the flavonoid compounds described herein in the present invention are from about 0.01% to about 20%, more preferably from about 0.1% to about 10%, still more preferably from about 0.5% to about 5%. anti-inflammatory agent

Anti-inflammatory agents can be added to the compositions of the present invention in safe and effective amounts, preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 5%, of the composition. The skin appearance improving benefits of the present invention can be enhanced by anti-inflammatory agents, as such agents contribute to a more even and acceptable skin tone or color. The exact amount of anti-inflammatory agent used in the composition will depend on the particular anti-inflammatory agent used, since the potency of such agents can vary widely.

Steroidal anti-inflammatory agents include, but are not limited to: corticosteroids such as hydrocortisone, hydroxyfluorocorticosterol, alpha-methyldexamethasone, dexamethasone phosphate, beclomethasone dipropionate, Clomethasone, acetone hydroxyprednisolone, fluorodihydroxymethylpregnanedione, deoxycorticosterone acetate, dexamethasone, dichlordeoxyprednisone, difloxadione , diflumetasone valerate, fluadrenolone, fludromethasone acetonide, fludrocortisone, flumetasone trimethylacetate, fluosinolone acetonide, fluocinolone acetate, flucortine butyl ester, fluocortine Colon, Fludroprednisolone Acetate, Fluoxetal, Halcinonide, Hydrocortisone Acetate, Hydrocortisone Butyrate, Methylprednisolone, Triamcinolone Acetonide, Cortisone, Cortisone Dotosone, flucetonide, hydrocortisone, difluorosone diacetate, acetone fluorescein acetonide, medrison, amcetafal, amcetafel, betamethasone and other amounts of esters, clorprednisone, chloroacetate Prednisone, clocotorolone, clescinolone, diclodextranone, diflunolone acetate, fluorodiclosone, 9-defluocinonide, flumethasone, methylflurone acetate, fluprednisone, Hydrocortisone valerate, hydrocortisone cypionate, hydrocortisone carbamate, methylprednisone, paramethasone, prednisone, prednisone, beclomethasone dipropionate, koji Anthiron and its mixtures. A preferred steroidal anti-inflammatory agent for use is hydroxycortisone.

A second class of anti-inflammatory agents useful in the present invention includes non-steroidal anti-inflammatory agents. Such anti-inflammatory agents include compounds well known to those skilled in the art. For the detailed disclosure of the chemical structure, synthesis, and side effects of non-steroidal anti-inflammatory agents, you can refer to authoritative works, including: Anti-inflammatory and anti-rheumatic drugs, K.D.Rainsford, Vol.I-III, CRC Press, Boca Raton, ( 1985), and Anti-Inflammatory Agents, Chemistry and Pharmacology 1, R.A. Scherrer et al., Academy Press, New York (1974).

Specific non-steroidal anti-inflammatory agents for use in the compositions of the present invention include, but are not limited to:

1) oxicams such as piroxicam, isoxathiamide, tenoxicam, sudoxicam and CP-14,304;

2) Salicylates such as acetylsalicylic acid, disalicylic acid, benoate, choline magnesium trisalicylate, safaprin, solprin, diflunisal and fentusal;

3) Acetic acid derivatives such as diclofenac, fenflurmic acid, indomethacin, sulindac, tolmetin, isoket acid, ethyl dihydrofuran acetic acid, dihydrooxydibenzothiepine Trieneacetic acid, zidometacin, acemetacin, fenticic acid, zomeacin, cloindacid, oxipinic acid, and felbinac;

4) Fenamates such as mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid and trofenamic acid;

5) Propionic acid derivatives such as ibuprofen, methoxymethyl naphthaleneacetic acid, benzoxaprofen, flurbiprofen, ketopropionic acid, phenoxyprofen, biphenbutyric acid, indole Profen, pirprofen, carprofen, oxaprofen, pranoprofen, miprofen, thioxaprofen, suprofen, alminoprofen, and tiaprofen.

6) Pyrazoles such as phenylbutazone, hydroxybutazone, fiprazone, alapropanzone, and trimetazol.

Mixtures of these non-steroidal anti-inflammatory agents and their cosmetically and/or pharmaceutically acceptable salts and esters of these agents may also be used. For example etofenamate (a derivative of flufenamic acid) is particularly suitable for topical application. Among these non-steroidal anti-inflammatory agents, ibuprofen, methoxymethyl naphthaleneacetic acid, flufenamic acid, etofenamate, aspirin, mefenamic acid, meclofenamic acid, piroxicam and felbinac are preferred ; ibuprofen, methoxymethyl naphthaleneacetic acid, etofenamate, aspirin and flufenamic acid are most preferred.

Finally, so-called "natural" anti-inflammatory agents may be used in the methods of the invention. These agents may be obtained as extracts from natural sources (eg, plants, fungi, microbial by-products) by appropriate physical and/or chemical isolation or may be produced synthetically. For example, candelilla wax, alpha-bisabolol, aloe vera, phytosterols (such as phytosterol), Manjistha (extracted from Rubia genus, especially Rubia Cordifolia plants), Guggal (extracted from Commiphora genus, especially Commiphora Mulkul plants ), kola extract, chamomile, red clover extract and sea whip extract.

Other anti-inflammatory agents useful herein include compounds of the Glycyrrhizae (genus/species Glycyrrhiza glabra) family, including glycyrrhetinic acid, glycyrrhizic acid and derivatives (eg, salts and esters) thereof. Suitable salts of the above compounds include metal salts and ammonium salts. Suitable esters include C2-C24 saturated or unsaturated esters of the acid, preferably C10-C24 esters, more preferably C16-C24 esters. Specific examples of the aforementioned substances include oil-soluble licorice extract, glycyrrhizic acid and glycyrrhetinic acid itself, glycyrrhizic acid monoammonium salt, glycyrrhizic acid monopotassium salt, glycyrrhizic acid dipotassium salt, 1-β-glycetinic acid, glycyrrhetinic acid Fatty esters, 3-stearyloxy-glycerate and 3-succinyloxy-β-glycerate disodium salt. Stearyl glycyrrhetinate is preferred. Anti-cellulite agent

The compositions of the present invention also contain a safe and effective amount of an anti-celling agent. Suitable agents include, but are not limited to, xanthine compounds (eg, caffeine, theophylline, theobromine, and aminobases). local anesthetic

The compositions of the present invention may also contain a safe and effective amount of a local anesthetic. Examples of local anesthetics include benzocaine, lidocaine, bupivacaine, chloroprocaine, tobucaine, eticaine, mepivacaine, tetracaine, dyclonine, Hexycaine, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically acceptable salts thereof. tanning actives

The compositions of the present invention may contain tanning actives. When present, preferred compositions contain from about 0.1% to about 20%, more preferably from about 2% to about 7%, still more preferably from about 3% to about 6%, by weight of dihydroxyacetone artificial tanning active.

该化合物可以单体和二聚体的混合物形式存在，其中二聚体主要为固态结晶状。加热或熔化时，二聚体破裂产生单体。这种二聚体向单体的转化也出现在水溶液中。二羟基丙酮在酸性pH值下更稳定是公所周知的。参见《默克索引》，第10版，第3167条，第463页(1983)，和《化妆品用二羟基丙酮》，E.Merck Technical Bulletin，03-304110，319897，180588。皮肤增白剂Dihydroxyacetone, also known as DHA or 1,3-dihydroxy-2-propanone, is a white to off-white crystalline powder. The substance can be represented by the chemical formula C ₃ H ₆ O ₃ and the following chemical structural formula:

The compound can exist as a mixture of monomers and dimers, where the dimers are mainly solid crystalline. When heated or melted, the dimer breaks down to produce monomers. This conversion of dimers to monomers also occurs in aqueous solutions. Dihydroxyacetone is known to be more stable at acidic pH. See The Merck Index, 10th Edition, Item 3167, p. 463 (1983), and Dihydroxyacetone for Cosmetics, E. Merck Technical Bulletin, 03-304110, 319897, 180588. skin brightener

Skin lightening agents may be included in the compositions of the present invention. When used, the compositions preferably contain from about 0.1% to about 10%, more preferably from about 0.2% to about 5%, and likewise preferably from about 0.5% to about 2%, by weight of a skin lightening agent. Suitable skin lightening agents include those known in the art, including kojic acid, arbutin, ascorbic acid and its derivatives (such as magnesium ascorbyl phosphate or sodium ascorbyl phosphate) and extracts (such as mulberry tree extract, placenta extract). Skin lightening agents suitable herein also include those described in PCT Application Serial No. 95/34280 in the name of Hillebrand (corresponding to PCT Application US 95/07432, filed 6/12/95) and in the name of Kvalnes, Mitchell A DeLong , the substance described in co-pending application serial number 08/390,152 (corresponding to PCT application 95/23780, published 9/8/95) in the name of Barton J Bradbury, Curtis B. Motley and John D Carter. Skin Comforting and Skin Healing Agents

Compositions of the present invention may contain skin comforting or skin healing agents. Skin comforting or skin healing agents suitable for use herein include pantothenic acid derivatives (including panthenol, dexpanthenol, ethyl panthenol), aloe vera, allantoin, bisabolol and dipotassium glycyrrhizinate. A safe and effective amount of a skin comforting or skin healing agent may be added to the compositions of the present invention, preferably from about 0.1% to about 30%, more preferably from about 0.5% to about 20%, still more preferably about 0.5% by weight of the formed composition to about 10%. Antimicrobial and antifungal actives

Compositions of the present invention may contain antimicrobial or antifungal actives. Such actives destroy microorganisms, preventing their growth or pathogenic behaviour. A safe and effective amount of an antimicrobial or antifungal active may be incorporated into the compositions of the present invention, preferably from about 0.001% to about 10%, more preferably from about 0.01% to about 5%, still more preferably from about 0.05% to about 2%.

Examples of antimicrobial and antifungal actives are: beta-lactams, quinolones, ciprofloxacin, norfloxacin, tetracyclines, erythromycin, amikacin, 2,4,4 '-Trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorodiphenylurea, phenoxyethanol, phenoxypropanol, phenoxyisopropanol, doxycycline, Amycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, hexamidine isethionate, metronidazole, pentamidine, gentamicin, kanamycin , clindamycin, methacycline, uropintor, minocycline, neomycin, netilmicin, paromomycin, streptomycin, tobramycin, diclobendazole, tetracycline Hydrochloride, Erythromycin, Zinc Erythromycin, Odorless Erythromycin, Erythromycin Stearate, Amikacin Sulfate, Doxycycline Hydrochloride, Shrimycin Sulfate, Gluconic Acid Lahebutate, Chloridine hydrochloride, aureomycin hydrochloride, oxytetracycline hydrochloride, clindamycin hydrochloride, ethambutol hydrochloride, metronidazole hydrochloride, pentamidine hydrochloride, gentamicin sulfate, kanamycin sulfate, hydrochloric acid Linomycin, oxytetracycline hydrochloride, urotropine hippurate, urotropine mandelate, minocycline hydrochloride, neomycin sulfate, netilmicin sulfate, paromomycin sulfate, chain sulfate Mycin, tobramycin sulfate, diclobendazole hydrochloride, ketaconazole, amanfadine hydrochloride, amanfadine sulfate, octopyrone, p-chloro-m-xylenol, nystatin, ringworm, zinc pyrithione and Clotrimazole.

Examples of a few preferred actives useful herein include salicylic acid, benzoyl peroxide, 3-hydroxybenzoic acid, glycolic acid, lactic acid, 4-hydroxybenzoic acid, acetylsalicylic acid, 2-hydroxybutyric acid , 2-Hydroxyvaleric acid, 2-Hydroxycaproic acid, cis-retinoic acid, trans-retinoic acid, retinol, phytic acid, N-acetyl-L-cysteine, lipoic acid, nonyl Diacid, arachidonic acid, benzoic acid peroxide, tetracycline, ibuprofen, naproxen, hydrocortisone, acetominophen, resorcinol, phenoxyethanol, phenoxypropanol, Phenoxyisopropanol, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorodiphenylurea, octopyrone, lidocaine hydrochloride Salt, clotrimazole, diclobendazole, ketoconazole, neocycin sulfate, and mixtures thereof. sunscreen actives

Skin exposure to UV rays can cause excessive scales and changes in the stratum corneum tissue. Accordingly, the compositions of the present invention optionally contain sunscreen actives. "Sunscreen active" as used herein includes sunscreens and physical sunscreens. Suitable sunscreen actives can be organic or inorganic.

Inorganic sunscreen actives useful herein include the following metal oxides: titanium dioxide having an average primary particle size of from about 15 nm to about 100 nm, zinc oxide having an average primary particle size of from about 15 nm to about 150 nm, and zinc oxide having an average primary particle size of from about 15 nm to about Zirconia of 150 nm, iron oxide having an average primary particle size of from about 15 nm to about 500 nm, and mixtures thereof. When used herein, inorganic sunscreen actives comprise from about 0.1% to about 20%, preferably from about 0.5% to about 10%, more preferably from about 1% to about 5%, by weight of the composition.

A wide variety of conventional organic sunscreen actives are suitable for use here. Segarin et al. in Cosmetic Science and Technology (1972), Chapter VIII, pp. 189ff, disclose a number of suitable actives. Specific suitable sunscreen actives include, for example, p-aminobenzoic acid, its salts and derivatives (ethyl, isobutyl, glyceryl esters, p-dimethylaminobenzoic acid), anthranilic acid esters (i.e. anthranil esters, methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl and cyclohexenyl esters); salicylates (pentyl, phenyl, benzyl, menthyl dipropylene glycol esters); cinnamic acid derivatives (menthyl and benzyl esters, (alpha-phenylcinnamonitrile; butylcinnamoyl acetonate); dihydroxycinnamic acid derivatives (umbrelliform ketone, methyl umbelliferone, methyl acetyl umbelliferone); trihydroxycinnamic acid derivatives (escin, methyl esculetin, daphnetin, and glucoside, escin and daphnetin); hydrocarbons (diphenylbutadiene, 1,2-stilbene); dibenzylideneacetone and benzylideneacetophenone; naphthol sulfonate (2-naphthol-3,6-disulfonic acid and 2- Naphthol-6,8-disulfonic acid sodium salt); dihydroxynaphthoic acid and its salts; o- and p-hydroxybiphenyl disulfonates; coumarin derivatives (7-hydroxy, 7-methyl , 3-phenyl); diazoles (2-acetyl-3-bromoindazole, phenylbenzoxazole, methylnaphthazole, various arylbenzothiazoles); quinine salts (bisulfate , sulfate, chloride, oleate and tannate); quinoline derivatives (8-hydroxyquinolinate, 2-phenylquinoline); hydroxyl or methoxy substituted benzophenones; uric acid and vilouric acid; tannic acid and its derivatives (e.g. hexaethyl ether); (butyl carbotol) (6-propyl piperonyl) ether; hydroquinone; Oxybenzone, benzoresorcinol, 2,2',4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, Otto Benzophenone; 4-Isopropyl-dibenzoylmethane; Butylmethoxybenzoylmethane; Ethyl cyanodiphenylacrylate; Octocrylene; 3-(4'-Methylbenzylideneterane -2-one), p-xylylenedicamphoronesulfonic acid, and 4-isopropyl-dibenzoylmethane.

Among them, 2-ethylhexyl p-methoxycinnamate (commercially available as PARSOL MCX), 4,4'-tert-butylmethoxydibenzoylmethane (commercially available as PARSOL 1789), 2-hydroxy-4-methoxy benzophenone, octyldimethyl-p-aminobenzoic acid, digalloyl trioleate, 2,2-dihydroxy-4-methoxybenzophenone, 4-(bis(hydroxypropyl)) Ethyl aminobenzoate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, 2-ethylhexyl salicylate, glyceryl p-aminobenzoate, 3,3 salicylic acid , 5-trimethylcyclohexyl ester, methyl anthranisate, p-dimethylaminobenzoic acid or aminobenzoate, 2-ethylhexyl p-dimethylaminobenzoate, 2-phenylbenzene Imidazole-5-sulfonic acid, 2-(p-dimethylaminophenyl)-5-sulfobenzoxazoic acid, octocrylene and mixtures of these compounds are preferred.

More preferred organic sunscreens for use in the compositions of the present invention are 2-ethylhexyl-p-methoxycinnamate, butylmethoxydibenzoylmethane, 2-hydroxy-4-methoxydiphenyl Ketones, 2-phenylbenzimidazole-5-sulfonic acid, octyldimethyl-p-aminobenzoic acid, octocrylene and mixtures thereof.

Also particularly suitable for use in the compositions of the present invention are sunscreens such as those disclosed in US 4,937,370, issued June 26, 1990 to Sabatelli and US 4,999,186, issued March 12, 1991 to Sabatelli and Spirnak. The sunscreens disclosed therein have two different chromophore moieties in one molecule which exhibit different absorption spectra of ultraviolet radiation. One of the chromophore moieties absorbs primarily in the UVB radiation range and the other chromophore moiety absorbs primarily in the UVA radiation range.

Preferred in this class of sunscreens are 4-N,N-(2-ethylhexyl)methylaminobenzoate of 2,4-dihydroxybenzophenone, N of 4-hydroxydibenzoylmethane, N-di-(2-ethylhexyl)-4-aminobenzoate, 4-N,N-(2-ethylhexyl)methylaminobenzoate of 4-hydroxydibenzoylmethane, 4-N,N-(2-ethylhexyl)methylaminobenzoate of 2-hydroxy-4-(2-hydroxyethoxy)benzophenone, 4-(2-hydroxyethyl)diphenyl 4-N,N-(2-ethylhexyl)methylaminobenzoate of formylmethane, N,N-di-( 2-Ethylhexyl)-4-aminobenzoate, and N,N-bis-(2-ethylhexyl)-4-aminobenzene of 4-(2-hydroxyethoxy)dibenzoylmethane Formic esters and mixtures thereof.

Particularly preferred sunscreen actives include 4,4'-tert-butylmethoxydibenzoylmethane, 2-ethylhexyl-p-methoxycinnamate, phenylbenzimidazole sulfonic acid and octocrylene.

Organic sunscreen actives are used in safe and effective amounts, typically from about 1% to about 20%, more preferably from about 2% to about 10%, by weight of the composition. The exact amount used will depend on the sunscreen active selected and the desired Sun Protection Factor (SPF). particulate matter

Compositions of the present invention may comprise particulate material, preferably metal oxides. These particles may be coated or uncoated, charged or uncharged. Charged particulate matter is disclosed in US5997887 (Ha et al.), incorporated by reference. Particulate materials useful for this include bismuth oxychloride, iron oxide, mica, barium sulfate and titanium dioxide treated mica, silica, nylon, polyethylene, talc, styrene, polypropylene, ethylene/acrylic acid copolymer, titanium dioxide, oxide Iron, bismuth oxychloride, sericite, aluminum oxide, silicone resin, barium sulfate, calcium carbonate, cellulose acetate, polymethyl methacrylate, and mixtures thereof.

Inorganic particulate materials such as _TiO2 , ZnO, or _ZrO2 are available from many commercial sources. An example of a suitable particulate material includes that available from US Cosmetics (TRONOX _TiO2 series, SAT-T CR837, rutile _TiO2 ). Preferably, the particulate material is present in the composition at a level of from about 0.01% to about 2%, more preferably from about 0.05% to about 1.5%, still more preferably from about 0.1% to about 1%, by weight of the composition. conditioner

Compositions of the present invention may contain conditioning agents selected from humectants, moisturizers or skin conditioning agents. A variety of materials are useful herein, each present at from about 0.01% to about 20%, more preferably from about 0.1% to about 10%, still more preferably from about 0.5% to about 7%, by weight of the composition. These substances include, but are not limited to, guanidine, urea, glycolic acid and glycolate salts (such as ammonium and quaternary alkylammonium salts); salicylic acid; lactic acid and lactate salts (such as ammonium and quaternary alkylammonium salts); Various forms of aloe vera (such as aloe vera gel); polyalcohols such as sorbitol, mannitol, xylitol, erythritol, glycerin, hexanetriol, butanetriol, propylene glycol, butylene glycol, hexylene glycol, etc.; polyols Ethylene glycol; sugars (eg, melibiose) and starches; sugar and starch derivatives (eg, alkoxylated glucose, fructose, glucosamine); hyaluronic acid; lactamide monoethanolamine; acetamide monoethanolamine; panthenol ; allantoin; and mixtures thereof. Also suitable for use herein are the propoxylated glycerols of US 4976953 (December 11, 1990) to Orr et al.

Also suitable herein are the various C ₁ -C ₃₀ mono- or polyesters of sugars and related materials. These esters are derived from a sugar or polyol moiety and one or more carboxylic acid moieties. These esters are also described in US 2,831,854 and US 4,005,195, Jandacek, Jan. 25, 1977; US 5,306,516, Apr. 26, 1994, Letton et al.; 5306515; US 5305514 issued April 26, 1994 to Letton et al; US 4797300 issued January 10, 1989 to Jandacek et al; US 3963699 issued June 15, 1976 to Rizzi et al; issued May 21, 1985 to Volpenhein US 4,518,772; and US 4,517,360, issued May 21, 1985 to Volpenhein.

Preferably, the conditioning agent is selected from the group consisting of urea, guanidine, sucrose polyesters, panthenol, dexpanthenol, allantoin and combinations thereof. structured reagent

The compositions herein, especially the emulsions herein, may contain structuring agents. Structuring agents are especially preferably present in the oil-in-water emulsions of the invention. Without being bound by theory, it is believed that the structuring agent helps to provide the composition with some rheology which helps to stabilize the composition. For example, structuring agents help form liquid crystal gel network structures. Structuring agents can also act as emulsifiers or surfactants. Preferred compositions of the present invention comprise from about 0.1% to about 20%, more preferably from about 0.1% to about 10%, most preferably from about 0.5% to about 9%, of one or more structuring agents.

Preferred structuring agents are those having an HLB of from about 1 to about 3 and a melting point of at least about 45°C. Suitable structuring agents are selected from saturated C14-C30 fatty alcohols, saturated C16 to C30 fatty alcohols (containing about 1 to about 5 moles of ethylene oxide), saturated C16-C30 diols, saturated C16-C30 monoglycerides, saturated C16-C30 hydroxy fatty acids, C14-C30 hydroxy and non-hydroxyl saturated fatty acids, C14-C30 saturated ethoxylated fatty acids, amines and alcohols containing from about 1 to about 5 moles of ethylene oxide glycol, with a monoglyceride content of at least 40 % C14-C30 saturated monoglycerides, C14-C30 saturated polyglycerides with about 1 to about 3 alkyl groups and about 2 to about 3 saturated glycerol units, C14-C30 monoglycerides, C14-C30 sorbitan Mono/Die Esters, C14-C30 Saturated Ethoxylated Sorbitan Mono/Die Esters (with about 1 to about 5 moles of ethylene oxide), C14-C30 Saturated Methyl Glycoside Esters, C14-C30 Saturated Sucrose Mono/Die Diesters, C14-C30 saturated ethoxylated methyl glycoside esters having from about 1 to about 5 moles of ethylene oxide, C14-C30 saturated polyglycosides having an average of 1 to 2 glucose units, and mixtures thereof, melting point At least about 45°C.

Preferred structuring agents of the present invention are selected from the group consisting of: stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, having an average of about 1 to about 5 oxirane Polyethylene glycol ethers of stearyl alcohol units, polyethylene glycol ethers of cetyl alcohol having an average of about 1 to about 5 ethylene oxide units, and mixtures thereof. More preferred structuring agents of the present invention are selected from the group consisting of stearyl alcohol, cetyl alcohol, behenyl alcohol, polyethylene glycol ethers of stearyl alcohol having an average of about 2 ethylene oxide units (Steareth-2) , Polyglycol ethers of cetyl alcohol having an average of about 2 ethylene oxide units and mixtures thereof. More preferred structuring agents are selected from stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, Steareth-2 and mixtures thereof. Thickening agents (including thickeners and gelling agents)

The compositions of the present invention may comprise one or more thickening agents, preferably from about 0.1% to about 5%, more preferably from about 0.1% to about 4%, and still more preferably from about 0.25% to about 3%, by weight of the composition. Thick reagent.

Non-limiting examples of thickening agents include materials selected from the group consisting of: a) carboxylic acid polymers

These polymers are crosslinked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acid, and salts and esters of these acrylic acid and substituted acrylic acid, wherein the crosslinking agent contains two or more carbon-carbon double bonds and derived from polyols. U.S.P No. 5,087,445 issued February 11, 1992 to Haffey et al; U.S.P No. 4,509,949 issued April 5, 1985 to Huang et al; U.S.P No. 2,798,053 issued July 2, 1957 to Brown for use in the present invention polymers are described in more detail. Refer again to "CTFA International Cosmetic Ingredient Dictionary", 4th Edition, 1991, pp.12 and 80.

Examples of commercially available carboxylic acid polymers useful in the present invention include carbomers, which are homopolymers of acrylic acid crosslinked with sucrose or allyl ethers of pentaerythritol. Commercially available carbopol preparations are Carbopol 900 series (such as Carbopol ^® 954) produced by Goodrich Corporation. In addition, other suitable carboxylic acid polymer reagents include copolymers of C10-C30 alkyl acrylates and one or more monomers, which may be acrylic acid, methacrylic acid or short chains thereof (i.e. C1-C4 Alcohol) ester, wherein the crosslinking agent is allyl ether of sucrose or pentaerythritol. These copolymers are known as acrylate/acrylic acid C10～C30 alkyl ester cross-linked polymers, and these commercially available polymers have Carbopol ^® 1342 produced by Goodrich, Carbopol ^® 1382, Pemulen TR-1 and Pemulen TR -2. In other words, the carboxylic acid polymer thickener used in the present invention can be selected from carbopol preparations, acrylate/C10-C30 alkyl acrylate cross-linked polymers, and mixtures thereof. b) Cross-linked polyacrylate polymer

The crosslinked polyacrylate polymers preferably included in the compositions of the present invention for use as thickeners or gelling agents include cationic and nonionic polymers, with cationic polymers being generally preferred. U.S.P 5,100,660 issued March 31, 1992 to Hawe et al; U.S.P 4,849,484 issued July 18, 1989 to Heard; U.S.P 4,835,206 issued May 30, 1989 to Farrar et al; issued December 9, 1986 to Glover et al U.S.P. 4,628,078 to Man; U.S. Patent 4,599,379 to Flesher et al., issued July 8, 1986; and Farrar et al. EP 228,868, published July 15, 1987. Examples of polyacrylate polymers and crosslinked cationic polyacrylate polymers. c) Polyacrylamide polymer

The compositions of the present invention may optionally contain polyacrylamide polymers, especially nonionic polyacrylamide polymers comprising substituted branched or unbranched polymers. Still more preferred among these polyacrylamide polymers is the nonionic polymer having the CTFA designation polyacrylamide and isoparaffin and lauryl ether-7, available under the tradename Sepigel 305 from Seppic Corporation (Fairfield, NJ). product.

Other polyacrylamide polymers useful in the present invention include multi-block copolymers of acrylamide and acrylamide substituted with acrylic acid and substituted acrylic acid. Commercially available examples of such multi-block copolymers include HypanSR150H, SS500V, SS500W, SSSA100H from Lipo Chemicals, Inc., (Patterson, NJ). d) polysaccharide

A variety of polysaccharides are used in the present invention. "Polysaccharide" means a gelling agent having a backbone of repeating sugar (ie, carbohydrate) units. Non-limiting examples of polysaccharide gelling agents include cellulose, carboxymethyl hydroxyethyl cellulose, cellulose acetate propionate carboxylate, hydroxyethyl cellulose, hydroxyethyl ethyl cellulose, hydroxypropyl cellulose , hydroxypropylmethylcellulose, methylhydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Alkyl-substituted celluloses can also be used in the present invention. In these polymers, the hydroxyl groups in the cellulosic polymer are hydroxyalkylated, preferably hydroxyethylated or hydroxypropylated, to form hydroxyalkylated cellulose, which is then formed from C10-C30 linear or branched alkyl groups are further modified by ether linkages. These polymers are typically ethers of hydroxyalkylcelluloses with C10-C30 linear or branched chain alcohols. The alkyl group used here can be selected from stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, cocoyl (that is, the alkyl group derived from the alcohol of coconut oil ), palmityl, oleyl, linoleyl, linolenic, castoryl, behenyl, and mixtures thereof. Preferred among the alkyl hydroxyalkyl cellulose ethers are those having the CTFA designation cetyl hydroxyethyl cellulose, which is an ether of cetyl alcohol and hydroxyethyl cellulose. Aqualon Corporation (Wilmington, DE) sells these materials under the tradename Natrosol ^(R) CS Plus.

Other polysaccharides used include scleroglucans containing (1-3) linked glucose units with linear chains of (1-6) linked glucose units for every three sugar units, a commercial example of which is Michel Clearogel TMCS 11 from Mercier Products Inc. (Mountainside, NJ). e) Glue

Other thickener gelling agents useful in the present invention include materials derived primarily from natural sources. Non-limiting examples of these gelling agent gums include gum arabic, agar, alginic acid, ammonium alginate, pullulan, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin , gellan gum, guar gum, guarhydroxypropyltrimonium chloride, hectorite grease, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl deacetate Propyl Guar Gum, Karaya Gum, Seaweed, Locust Bean Gum, Natto Gum, Potassium Alginate, Potassium Carrageenan, Propylene Glycol Alginate, Sclerotin Gum, Sodium Carboxymethyl Dextran, Carrageenan Sodium gum, tragacanth gum, xanthan gum, and mixtures thereof.

Preferred compositions of the present invention include a thickening agent selected from the group consisting of carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers and mixtures thereof, more preferably carboxylic acid polymers, polyacrylamide polymers and mixtures thereof.

IV. Dermatologically Acceptable Carriers

The topical compositions of the present invention comprise a dermatologically acceptable carrier. Here the term "dermatologically acceptable carrier" means that the carrier is suitable for topical application to keratinous tissue, has good aesthetic properties, is compatible with the actives of the invention and any other components, and does not cause any undesired safety or toxicity concerns. A safe and effective amount of carrier is from about 50% to about 99.99%, preferably from about 80% to about 99.9%, more preferably from about 90% to about 98%, still more preferably from about 90% to about 95%, by weight of the composition.

Carriers can take many forms. For example, emulsion carriers including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions are suitable herein.

Preferred carriers include emulsions, such as oil-in-water emulsions, water-in-oil emulsions and water-in-silicone emulsions. It will be understood by those skilled in the art that a given component will distribute primarily in the water or oil/silicone phase, depending on the water solubility/dispersibility of the component in the composition. Oil-in-water emulsions are especially preferred.

Emulsions of the present invention generally comprise the solutions described above and lipids or oils. Lipids and oils can be of animal, vegetable or petroleum origin, and can be natural or synthetic (ie, man-made). Preferred emulsions also contain humectants such as glycerin. The emulsion preferably also contains from about 1% to about 10%, more preferably from about 2% to about 5%, of an emulsifier, based on the weight of the carrier. Emulsifiers can be nonionic, anionic or cationic. Suitable emulsifiers are disclosed, for example, in USP 3755560, issued August 28, 1973 to Dickert et al; USP 4421769, issued December 20, 1983 to Dixon et al; and McCutcheon's Detergents and Emulsifiers, North American Edition, p. 317 - 324 pages (1986).

The emulsion may also contain an antifoaming agent to minimize foam formation when applied to keratinous tissue. Antifoaming agents include high molecular weight polysiloxanes, and others known in the art to be useful therefor.

Suitable emulsions can have a wide range of viscosities, depending on the desired product form. Preferred exemplary low viscosity emulsions have a viscosity of about 50 centistokes or less, more preferably about 10 centistokes or less, most preferably about 5 centistokes or less.

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

A) Water-in-silicone emulsion

Water-in-silicone emulsions contain a continuous silicone phase and a dispersed aqueous phase.

(1) Continuous polysiloxane phase

Preferred water-in-silicone emulsions of the present invention comprise from about 1% to about 60%, preferably from about 5% to about 40%, more preferably from about 10% to about 20%, by weight, of the continuous silicone phase. The continuous polysiloxane phase exists as an external phase which contains or surrounds the discontinuous aqueous phase described below.

The continuous silicone phase contains organopolysiloxane oil. A preferred oil-in-silicone emulsion system is formulated to provide an oxidatively stable carrier for the retinoid. The continuous silicone phase of these preferred emulsions comprises from about 50% to about 99.9% by weight organopolysiloxane oil and less than about 50% by weight non-silicone oil. In an especially preferred embodiment, the continuous polysiloxane phase comprises at least about 50%, preferably from about 60% to about 99.9%, more preferably from about 70% to about 99.9%, and especially preferably from 80% to about 99.9% polyorganic Silicone-based oils, and up to about 50% non-silicone oils, preferably less than about 40%, more preferably less than about 30%, more preferably less than about 10%, and still more preferably less than about 2%, based on the continuous silicone Oxane phase weight. These preferred emulsion systems provide greater oxidative stability to retinoids over longer periods of time than comparable water-in-oil emulsions containing lower concentrations of organosiloxane oil. The concentration of non-silicone oils in the continuous silicone phase is minimized or avoided together to further enhance the oxidative stability of the selected retinoids in the composition. Oil-in-silicone emulsions of this type are described in PCT Application WO 97/21423, published June 19, 1997.

The organopolysiloxane oil in the composition can be a volatile non-volatile or a mixture of volatile and non-volatile polysiloxanes. The term "nonvolatile" refers herein to those polysiloxanes which are liquid at room temperature and have a flash point (at one atmosphere) of 100°C or higher. The term "volatile" refers herein to all other silicone oils. Suitable organopolysiloxanes can be selected from a wide variety of polysiloxanes spanning a wide range of volatility and viscosity. Suitable polyorganosiloxane oils include polyalkylsiloxanes, cyclic polyalkylsiloxanes and polyalkylarylsiloxanes.

The polyalkylsiloxanes in the composition include polyalkylsiloxanes having a viscosity of from about 0.5 to about 1,000,000 centistokes at 25°C. This type of polyalkylsiloxane can be represented by the general formula R ₃ SiO[R ₂ SiO] _x SiR ₃ , wherein R is a C1-C30 alkyl group (preferably R is methyl or ethyl, more preferably methyl; in the same There may also be different alkyl groups in the molecule), x is an integer from 0 to about 10,000, x can be selected to obtain the desired molecular weight up to about 10,000,000 or more. Commercially available polyalkylsiloxanes include polydimethylsiloxanes, also known as dimethicones, examples of which include the Vicasil ^(R) series sold by General Electric Company, and the Dow Corning( ^R) 200 series sold by Dow Corning Corporation. Specific examples of suitable polydimethylsiloxanes include Dow ^Corning® 200 fluid, which has a viscosity of 0.65 centistokes and a boiling point of 100°C, Dow ^Corning® 225 fluid, which has a viscosity of 10 centistokes and a boiling point of greater than 200°C, and Dow Corning® ²⁰⁰ Fluids with viscosities of 50, 350 and 12,500 centistokes and boiling points greater than 200°C. Suitable dimethicones include those represented by the formula (CH ₃ ) ₃ SiO[(CH ₃ ) ₂ SiO] _x [CH ₃ RSiO] _y Si(CH ₃ ) ₃ wherein R is 2 to 30 carbon atoms The linear or branched chain, x and y are each an integer of 1 or more, and x and y can be selected to obtain a desired molecular weight up to about 10,000,000 or more. Examples of these alkyl-substituted dimethicones include cetyl dimethicone and lauryl dimethicone.

Cyclic polyalkylsiloxanes suitable for use in the composition include those represented by the formula [ _SiR2 -O] _n , wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl), and n is An integer of about 3 to about 8, more preferably an integer of about 3 to about 7, and most preferably an integer of about 4 to about 6. When R is methyl, these materials are generally known as cyclomethicones. Commercially available cyclomethicones include Dow Corning ^® 244 fluid, viscosity 2.5 centistokes, boiling point 172°C, which mainly contains cyclomethicone (i.e., n=4), Dow Corning ^® 344 fluid, viscosity 2.5 centistokes , boiling point 178°C, it mainly contains cyclomethicone (ie n=5), Dow Corning ^® 245 fluid, viscosity 4.2 centistokes, boiling point 205°C, it mainly contains cyclomethicone and cyclomethicone A mixture of pentapolysiloxane (i.e. n = 4 and 5), and ^DowCorning® 345 fluid, viscosity 4.5 centistokes, boiling point 217 ° C, it mainly contains cyclomethicone, cyclomethicone and Mixtures of cyclomethicones (ie n = 4, 5 and 6).

Also suitable are materials such as trimethylsiloxysilicate, which is a polymer corresponding to the general formula [(CH ₂ ) ₃ SiO _1/2 ] _x [SiO ₂ ] _y , where x is from about 1 to about 500 is an integer, y is an integer from about 1 to about 500. Commercially available trimethylsiloxysilicate is sold as a mixture with the dimethicone DowCorning ^(R) 593 Fluid.

Dimethiconol is also suitable for use in the composition. Such compounds can be represented by chemical formulas R ₃ SiO[R ₂ SiO] _x SiR ₂ OH and HOR ₂ SiO[R ₂ SiO] _x SiR ₂ OH, wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl base) and x is an integer from 0 to about 500, x is selected to obtain the desired molecular weight. Commercially available dimethicones are generally sold as mixtures with dimethicone or cyclomethicone (eg Dow Corning ^(R) 1401, 1402 and 1403 fluids).

Polyalkylaryl siloxanes are also suitable for use in the composition. Especially polymethylphenylsiloxanes having a viscosity of from about 15 to about 65 centistokes (25°C).

Preferred polyorganosiloxanes herein are selected from the group consisting of polyalkylsiloxanes, alkyl substituted dimethicones, cyclomethicones, trimethicone silicates, dimethicone Silicone alcohols, polyalkylaryl siloxanes and mixtures thereof. More preference is given here to polyalkylsiloxanes and cyclomethicones. Preferred among the polyalkylsiloxanes are dimethicones.

As noted above, the continuous silicone phase may contain one or more non-silicone oils. The concentration of non-silicone oils in the continuous silicone phase is preferably minimized or avoided together to even further enhance the oxidative stability of the selected retinoid in the composition. Suitable non-silicone oils have a melting point of about 25°C or less at about 1 atmosphere. Examples of non-silicone oils for the continuous silicone phase are those well known in the chemical art of topical personal care products, where the product is in the form of a water-in-oil emulsion, such as mineral oils, vegetable oils, synthetic oils, Semi-synthetic oil etc.

(2) Dispersed water phase

The topical compositions of the present invention comprise from about 30% to about 90%, more preferably from about 50% to about 85%, most preferably from about 70% to about 80%, of a dispersed aqueous phase. In emulsion technology, the term "dispersed phase" is a term well known to those skilled in the art and refers to small particles or droplets suspended or surrounded in a continuous phase. The dispersed phase is also called the internal or discontinuous phase. The dispersed aqueous phase is a dispersion of water droplets or particles suspended or surrounded in the above-mentioned continuous polysiloxane phase.

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

The topical compositions of the present invention generally comprise from about 25% to about 90%, preferably from about 40% to about 80%, more preferably from about 60% to about 80%, water in the dispersed aqueous phase, by weight of the composition.

(3) Emulsifier for dispersing the water phase

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

A variety of emulsifiers can be employed herein to form the preferred water-in-silicone emulsions. Known or conventional emulsifiers can be used in the composition provided that the emulsifier selected is chemically and physically compatible with the ingredients of the composition of the invention and produces the desired dispersing properties. Suitable emulsifiers include silicone emulsifiers, silicone-free emulsifiers and mixtures thereof, which are known to those skilled in the topical personal care product art. Preferably, these emulsifiers have an HLB value of less than about 14, more preferably from about 2 to about 14, still more preferably from about 4 to about 14. Emulsifiers with HLB values outside this range can be used in combination with other emulsifiers to achieve a combined effective weight average HLB within this range.

Silicone emulsifiers are preferred. A variety of silicone emulsifiers are used herein. These silicone emulsifiers are generally organically modified organopolysiloxanes, also known as silicone surfactants by those skilled in the art. Suitable silicone emulsifiers include dimethicone copolyols. These materials are polydimethylsiloxanes which have been modified to include polyether side chains such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and Polyether chains that are part of ethylene oxide and propylene oxide. Other examples include alkyl-modified dimethicone copolyols, ie, compounds containing C2-C30 side chains. Other suitable dimethicone copolyols include those having various pendant cationic, anionic, amphoteric and zwitterionic moieties.

The dimethicone copolyol emulsifier used here can be represented by the following formula:

Wherein R is C1-C30 linear, branched or cyclic alkyl, and ^R2 is selected from groups consisting of:

--(CH ₂ ) _n --O --(CH ₂ CHR ³ O) _m --H,

and

--(CH ₂ ) _n --O--(CH ₂ CHR ³ O) _m --(CH ₂ CHR ⁴ O) _o --H,

wherein n is an integer from ^{3 to} about 10; R and R are ^selected from groups consisting of H and C1-C16 straight or branched chain alkyl such that R and ^R are not simultaneously the same; and m, o, x and y are selected such that the molecule has an overall molecular weight of from about 200 to about 10,000,000, and m, o, x, and y are each selected from zero or greater integers such that m and o are not simultaneously zero, and z is independently selected from 1 or Larger integer. It is recognized that positional isomers of these copolyols are available. The above chemical representation of the ^R2 moiety containing the ^R3 and ^R4 groups is not limiting, but is shown for convenience.

The silicone surfactants shown in the structure in the previous paragraph, where ^R2 is -( _CH2 ) _n - ^OR5 , where ^R5 is a cationic, anionic, amphoteric or zwitterionic moiety, may also be used, although It is not strictly classified as a dimethicone copolyol.

Non-limiting examples of dimethicone copolyols and other silicone surfactants useful herein as emulsifiers include: Dimethicone polyether copolymers having polyethylene oxide side chains, Polydimethylsiloxane polyether copolymer with polypropylene oxide side chain, polydimethylsiloxane polyether copolymer with polyethylene oxide and polypropylene oxide mixed side chain, (Ethylene)(propylene) mixed side chain polydimethylsiloxane polyether copolymer, polydimethylsiloxane polyether copolymer with organobetaine side chain, carboxylate (salt) side chain Polydimethylsiloxane polyether copolymers, polydimethylsiloxane polyether copolymers with quaternary ammonium salt side chains, and side groups containing C2-C30 linear, branched or cyclic alkyl moieties Further modifications of the above-mentioned copolymers. Examples of dimethicone copolyols sold by Dow Corning for use herein are Dow ^Corning® 190, 193, Q2-5220, 2501 Wax, 2-5324 Fluid, and 3225C (the latter available as a mixture with cyclomethicone). for sale). Cetyl dimethicone copolyol is commercially available as a mixture with polyglyceryl-4 isostearate (and) hexyl laurate as ABIL ^(R) WE-09 (available from Goldschmidt). Cetyl dimethicone copolyol is also commercially available as a mixture with hexyl laurate (and) polyglyceryl-3 oleate (and) cetyl dimethicone, sold as ABIL ^(R) WS-08 is sold (also from Goldschmidt). Other non-limiting examples of dimethicone copolyols include lauryl dimethicone copolyol, dimethicone copolyol acetate, dimethicone copolyol Alcohol Adipate, Dimethicone Copolyol Amine, Dimethicone Copolyol Behenate Dimethicone Copolyol Butyl Ether, Dimethicone Copolyol Hydroxystearate, Dimethicone Copolyol Isostearate, Dimethicone Copolyol Laurate, Dimethicone Copolyol Methyl Ether, Dimethicone Copolyol Methyl Ether, Methicone Copolyol Phosphate, and Dimethicone Copolyol Stearate. See International Cosmetic Ingredient Dictionary, 5th Edition, 1993.

The dimethicone copolyol emulsifiers used here are for example described in USP 4960764, authorized on October 2, 1990 to Figueroa, Jr. et al; European Patent EP330369, published on August 3, 1989, belonging to SanoGueira; G.H. Dahms et al., "New formulation possibilities offered by silicone copolyols", Cosmetics & Toiletries, Vol. 110, pp. 91-100, March 1995; M.E. Carlotti et al., "W/O-S Emulsions The optimization of ester structure and quantitative relationship between emulsion properties", Journal of Dispersion Science and Technology, 13 (3), 315-336 (1992); P. Hameyer's "Organic and organopolysiloxane emulsification Comparable technical study of surfactants in cosmetic water-in-oil emulsion formulations", HAPPI28 (4), pages 88-128 (1991); J.Smid-Korbar et al. Effectiveness and suitability", Provisional Communication, International Journal of Cosmetic Science, 12, 135-139 (1990); and D.G. Krzysik et al., "New polysiloxane emulsifiers for water-in-oil systems", Pharmaceuticals & Cosmetics Industry, Vol. 146(4), pp. 28-81 (April 1990).

Silicone-free emulsifiers used here include various nonionic and anionic emulsifiers, such as sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1-C30 fatty acid esters of C1-C30 fatty alcohols, Alkoxylated derivatives of C1-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fatty alcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 esters of polyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps and mixtures thereof. Other suitable emulsifiers are for example described in McCutcheon's Detergents and Emulsifiers, North American Edition (1986), published by Allured Publishing Company; USP 5011681, issued April 30, 1991 to Ciotti et al; USP 4421769, December 20, 1983 to Dixon et al.; and USP 3,755,560, issued Aug. 28, 1973 to Dickert et al.

Non-limiting examples of these silicone-free emulsifiers include: Polyethylene Glycol 20 Sorbitan Monolaurate (Polysorbate 20), Polyethylene Glycol 5 Soy Sterol, Steareth-20, Ceteareth-20, PPG-2 Methanol Glucose Ether Distearate, Ceteth-10, Polysorbate80, Cetyl Phosphate, Potassium Cetyl Phosphate, Diethanolamine Cetyl Phosphate, Polysorbate 60, Glyceryl Stearate, PEG-100 Stearate, Polyoxyethylene 20 sorbitan trioleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4 isostearate, hexyl laurate , Steareth-20, Ceteareth-20, PPG-2 Methyl Glucose Ether Distearate, Ceteth-10, Diethanolamine Cetyl Phosphate, Glyceryl Stearate, PEG-100 Stearate, and mixtures thereof.

B) Oil-in-water emulsion

Other preferred topical carriers include oil-in-water emulsions, which have a continuous aqueous phase and dispersed therein a hydrophobic, water-insoluble phase (oil phase). Examples of suitable oil-in-water emulsion carriers are described in US 5,073,371 and US 5,073,372, issued December 17, 1991 to Turner, D.J. et al. A particularly preferred oil-in-water emulsion containing a structuring agent, a hydrophilic surfactant and water is described in detail below.

(1) Structural reagents

Preferred oil-in-water emulsions contain structuring agents to aid in the formation of the liquid crystal gel network structure. Without being bound by theory, it is believed that the structuring agent helps provide the rheology of the composition to produce composition stability. Structuring agents can also act as emulsifiers or surfactants. Preferred compositions of the present invention contain from about 0.5% to about 20%, more preferably from about 1% to about 10%, still more preferably from about 1% to about 5%, by weight of the composition, of a structuring agent.

Preferred structuring agents of the present invention include stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, with an average of about 1-5 ethylene oxide units Selected from the group consisting of polyethylene glycol ethers of stearyl alcohol, polyethylene glycols of cetyl alcohol having an average of about 1-21 ethylene oxide units, and mixtures thereof. Preferred structuring agents are polyethylene glycol ethers (steareth-2) consisting of stearyl alcohol, cetyl alcohol, behenyl alcohol, and stearyl alcohol with an average of about 2 ethylene oxide units. , polyethylene glycol ethers of stearyl alcohol with an average of about 21 ethylene oxide units (steareth-21), polyethylene glycol ethers of cetyl alcohol with an average of about 2 ethylene oxide units, and Choose from a collection consisting of a mixture of them. More preferred structuring agents are selected from the group consisting of stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, steareth-2, steareth-21, and mixtures thereof.

(2) Hydrophilic surfactants

Preferred oil-in-water emulsions contain at least one hydrophilic surface in an amount between about 0.05% and 10%, preferably between about 1% and 6%, more preferably between about 1% and 3%. The active agent, which is a hydrophobic material dispersed in the aqueous phase (as a percentage by weight of the topical carrier). The surfactant must be at least hydrophilic to be sufficiently dispersible in water.

Preferred hydrophilic surfactants are selected from nonionic surfactants. Those that can be broadly defined as the condensation products of long-chain alcohols (such as C8-C30 alcohols) with sugar or starch polymers, ie, glycosides, are suitable for use in the nonionic surfactants of the present invention. Such compounds can be represented by the formula (S)n-O-R, wherein S is a sugar moiety such as glucose, fructose, mannose and galactose, n is an integer from about 1 to about 1000, and R is a C8-C30 alkyl group. Examples of long chain alcohols from which the alkyl group is derived include decyl alcohol, cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol, and the like. Preferred examples of these surfactants include those compounds wherein S is a glucose moiety, R is a C8-C20 alkyl group, and n is an integer from about 1 to about 9. Commercially available examples of these surfactants include decyl polyglucoside (APG325CS available from Henkel Corporation) and lauryl polyglucoside (APG600CS and 625CS available from Henkel Corporation).

Other suitable nonionic surfactants include condensation products of alkylene oxides with fatty acids (ie, alkylene oxide esters of fatty acids). These substances have _the general formula RCO(X)nOH, where R is a C10-C30 alkyl group and X is _-OCH2CH2- (i.e. derived from ethylene glycol or oxide) or _-OCH2- CH- _CH3- (ie derived from propylene glycol or oxide), n is an integer from about 6 to about 200. Other nonionic surfactants are condensation products of alkylene oxides with 2 moles of fatty acids (ie di-fatty acid esters of alkylene oxides). _The general formula for such substances is RCO(X)nOOCR, where R is a C10-C30 alkyl group and X is _-OCH2CH2- (ie, derived from ethylene glycol or oxide), or _{-OCH2CHCH 3} - (ie derived from propylene glycol or oxide), n is an integer from about 6 to about 100. Other nonionic surfactants are the condensation products of alkylene oxides with fatty alcohols (ie, alkylene oxide ethers of fatty alcohols). The _general formula for such substances is R(X)nOR', where R is a C10-C30 alkyl group and X is _-OCH2CH2- (ie derived from ethylene glycol or oxide) or _{-OCH2CHCH 3} - (ie, derived from propylene glycol or oxide), n is an integer from about 6 to about 100 and R' is H or a C10-C30 alkyl group. There are other nonionic surfactants that are products of condensation of alkylene oxides with both fatty acids and fatty alcohols [i.e., one end of the polyoxyalkylene moiety is esterified with fatty acid and the other end is etherified with fatty alcohol (i.e., linked via an ether bond. )]. The general formula for such substances is RCO(X)nOR', where R and R' are C10-C30 alkyl groups, and X is -O-CH ₂ CH ₂ - (ie, derived from ethylene glycol or oxide) or _-OCH2CHCH3- (ie, derived from propylene glycol or oxide), n is an integer _from about 6 to about 100. Non-limiting examples of these alkylene oxide derived nonionic surfactants include ceteth-6, ceteth-10, ceteth-12, ceteraeth-6, ceteraeth-10, ceteraeth-12, steareth-6, steareth-10, steareth-12, steareth-21, PEG-6 stearate, PEG-10 stearate, PEG-100 stearate, PEG-12 stearate, PEG-20 glyceryl stearate, PEG -80 glyceryl tallowate, PEG-10 glyceryl stearate, PEG-30 glyceryl cocoate, PEG-80 glyceryl cocoate, PEG-200 glyceryl tallowate, PEG-8 dilaurate, PEG-10 distearate and mixtures thereof.

Other suitable nonionic surfactants also include polyhydroxy fatty acid amide surfactants corresponding to the following structural formulas:

In the formula, R ¹ is H, C1-C4 alkyl, 2-hydroxyethyl, 2-hydroxypropyl, preferably C1-C4 alkyl, more preferably methyl or ethyl, most preferably methyl; R ² is C5- C31 alkyl or alkenyl, preferably C7-C19 alkyl or alkenyl, more preferably C9-C17 alkyl or alkenyl, most preferably C11-C15 alkyl or alkenyl; Z is at least 3 hydroxyl groups Polyhydroxyl hydrocarbyl moieties having a linear hydrocarbyl chain directly attached to the chain or their alkoxylated (preferably ethoxylated or propoxylated) derivatives. Preferably Z is selected from the sugar moieties of glucose, fructose, maltose, lactose, galactose, mannose, xylose and mixtures thereof. A particularly preferred surfactant corresponding to the above structure is cocoalkyl N-methylglucosideamide (ie, wherein the ^R2CO- moiety is derived from coconut fatty acid). Methods for preparing polyhydroxy fatty acid amide compositions have been disclosed, for example, in British Patent Specification 809060 (Thomas Hedley & Co. Ltd. published on February 18, 1959), U.S. Patent 2,965,576 by ER Wilson (issued on December 20, 1960), AM Schwarts US Patent 2,703,798 (issued March 8, 1955), Piggott US Patent 1,985,424 (issued December 25, 1934), the contents of which are incorporated herein by reference in their entirety.

Preferred among the nonionic surfactants are steareth-21, ceteareth-21, ceteareth-12, sucrose cocoate, steareth-100, PEG-100 stearate and mixtures thereof.

Other suitable nonionic surfactants include sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1-C30 fatty acid esters of C1-C30 fatty alcohols and their alkoxylated derivatives, C1- Alkoxylated ethers of C30 fatty alcohols, polyglycerol esters of C1-C30 fatty acids, C1-C30 esters of polyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty ethers of phosphates, fatty acids Amides, lactyl esters and mixtures thereof. Non-limiting examples of these emulsifiers include: Polyethylene Glycol 20 Sorbitan Monolaurate (Polysorbate 20), Macrogol 3 Soy Sterol, Steareth-20, Ceteareth-20, PPG-2 Methyl Glucose Ether Distearate, Ceteth-10, Polysorbate 80, Cetyl Phosphate, Potassium Cetyl Phosphate, Cetyl Diethanolamine Phosphate, Polysorbate 60, Glyceryl Stearate, Polyoxyethylene 20 Sorbitan Tris Oleate (Polysorbate 85), Sorbitan Monolaurate, Polyoxyethylene 4 Lauryl Ether Sodium Stearate, Polyglyceryl-4 Stearate, Hexyl Laurate, PPG-2 Methyl Glucose Ether distearate, PEG-100 stearate and mixtures thereof.

Another group of nonionic surfactants useful herein includes fatty acid ester blends based on a mixture of fatty acid esters of sorbitan or sorbitol and sucrose fatty acid esters, the fatty acid in each case being preferably C8-C24 , more preferably C10-C20. A preferred fatty acid ester emulsifier is a blend of sorbitan or sorbitol C16-C20 fatty acid ester and sucrose C10-C16 fatty acid ester, especially sorbitan stearate and sucrose cocoate. These are commercially available from ICI Corporation under the tradename Arlatone 2121.

Other surfactants suitable for use herein include a wide variety of cationic, anionic, zwitterionic and amphoteric surfactants such as are known in the art and discussed in detail below. See, McCutcheon's Detergents and Emulsifiers (North American Edition), Allured Publishing Corporation, 1986; U.S. Patent No. 5,011,681, issued April 30, 1991 to Ciotti; U.S. Patent No. 5,011,681, issued December 20, 1983 to Dixon et al. No. 4,421,769; US Patent No. 3,755,560 to Dickert et al., issued Aug. 28, 1973; these documents are hereby incorporated by reference in their entirety. The hydrophilic surfactants used herein may comprise a single surfactant or any combination of suitable surfactants. The exact choice of surfactant will depend upon the pH of the composition and the presence of other ingredients.

Cationic surfactants useful herein include dialkyl quaternary ammonium compounds, examples of which are described in U.S. Patent No. 5,151,209; U.S. Patent No. 5,151,210; U.S. Patent No. 5,120,532; U.S. Patent No. 4,387,090; U.S. Patent No. 3,155,591; U.S. Patent No. 3,929,678; U.S. Patent No. 3,959,461; McCutcheon's Detergent and Emulsifier (North American Edition) of MC Publishing Co. in 1979; Interscience Publishers published in New York in 1949 The surface of Schwartz et al. Active agents and their chemistry and technology. All of these documents are incorporated herein by reference. Cationic surfactants useful herein also include cationic ammonium salts having the formula:

Wherein, R ₁ is an alkyl group containing about 12 to 30 carbon atoms, or an aromatic aryl or alkaryl group containing about 12 to 30 carbon atoms; R ₂ , R ₃ and R ₄ are each from hydrogen , an alkyl group containing about 1 to 22 carbon atoms or an aromatic aryl or alkaryl group containing about 12 to 22 carbon atoms; X is any matching anion, more preferably selected from chlorine, bromine, Select from the set consisting of iodine, acetate, phosphate, nitrate, sulfate, methylsulfate, ethylsulfate, tosylate, lactate, citrate, glycolate, and mixtures thereof. In addition, the alkyl groups _R1 , _R2 , _R3 and _R4 may also contain ester linkages and/or ether linkages, or hydroxyl or amino substituents (for example, the alkyl groups may contain polyethylene glycol and polypropylene glycol moieties).

More preferably, _R1 is an alkyl group containing about 12 to 22 carbon atoms; _R2 is selected from H or an alkyl group containing about 1 to 22 carbon atoms; _R3 and _R4 are selected from hydrogen, containing about 1 to 3 carbon atoms selected from the alkyl group; X is as described above.

Most preferably, R ₁ is an alkyl group containing about 12 to 22 carbon atoms; R ₂ , R ₃ and R ₄ are selected from hydrogen, an alkyl group having about 1 to 3 carbon atoms; X is as previously described stated.

As an alternative, other useful cationic emulsifiers include aminoamides in which R ₁ is replaced by R ₅ CO-(CH ₂ ) _n - in the above structure, where R ₅ is an alkane containing about 12 to 22 carbon atoms. n is an integer of about 2-6, preferably an integer of about 2-4, more preferably an integer of about 2-3. Non-limiting such cationic emulsifiers include stearamidopropyl phosphoric acid PG-dimonium chloride, behenyl amidopropyl chloride PG-dimonium, stearamidopropyl ethosulfate ethyl dimonium , stearamidopropyl dimethyl (tetradecyl acetic acid) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium toluenesulfonate, stearamidopropyl dimethyl ammonium chloride, hard Fatty amidopropyl dimethyl ammonium lactate and mixtures thereof. Especially preferred is behenylamidopropyl PG-dimonium chloride.

A few non-limiting examples of quaternary ammonium cationic emulsifiers can be selected from cetyl ammonium chloride, cetyl ammonium bromide, lauryl ammonium chloride, lauryl ammonium bromide, hard Fatty ammonium chloride, stearyl ammonium bromide, cetyl dimethyl ammonium chloride, cetyl dimethyl ammonium bromide, lauryl dimethyl ammonium chloride, lauryl Dimethyl ammonium bromide, stearyl dimethyl ammonium chloride, stearyl dimethyl ammonium bromide, cetyl trimethyl ammonium chloride, cetyl trimethyl ammonium bromide, Dialkyltrimethylammonium chloride, dodecyltrimethylammonium bromide, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, dodecyldimethylammonium chloride Ammonium, Stearyl Dimethyl Cetyl Ditallow Dimethyl Ammonium Chloride, Di-Cetyl Ammonium Chloride, Di-Cetyl Ammonium Bromide, Di-Dodecyl Chloride ammonium chloride, di-lauryl ammonium bromide, di-stearyl ammonium chloride, di-stearyl ammonium bromide, di-hexadecyl methyl ammonium chloride, di-hexadecyl methyl ammonium Ammonium Bromide, Di-Lauryl Methyl Ammonium Chloride, Di-Lauryl Methyl Ammonium Bromide, Di-Stearyl Methyl Ammonium Chloride, Di-Stearyl Methyl Ammonium Bromide and those examples selected from the collection consisting of their mixtures. Other quaternary ammonium salts include those in which the C12-C30 alkyl carbon chain is derived from tallow fatty acid or coconut fatty acid. The term "tallow" refers to an alkyl group derived from tallow fatty acids (usually hydrogenated tallow fatty acids), usually containing a mixture of alkyl groups in the range of C16 to C18, and the term "coconut oil" refers to An alkyl group derived from coconut fatty acids usually containing a C12-C14 alkyl mixture. Examples of several quaternary ammonium salts derived from these tallows and coconuts include ditallow dimethyl ammonium chloride, ditallow dimethyl ammonium methyl sulfate, di(hydrogenated tallow) dimethyl Ammonium Chloride, Di(Hydrogenated Tallow) Dimethyl Ammonium Acetate, Di-Tallow Dimethyl Ammonium Phosphate, Di-Tallow Dimethyl Ammonium Nitrate, Di(Coco-Alkyl) Dimethyl Ammonium Chloride, Di (Cocoalkyl) Dimethyl Ammonium Bromide, Tallow Ammonium Chloride, Coco Ammonium Chloride, PG-dimonium Stearamidopropyl Ethyl Sulfate, Dimonium Stearamidopropyl Ethyl Sulfate, Stearamidopropyl Ethyl Dimonium Fatty amidopropyl dimethyl (tetradecyl acetic acid) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyl dimethyl ammonium chloride, stearamide Choose from the group consisting of propyl dimethyl ammonium lactate and mixtures thereof. An example of a quaternary ammonium compound having an alkyl group having an ester bond is ditallowyloxyethyldimethylammonium chloride.

A more preferred cationic surfactant can be obtained from behenyl amidopropyl chloride PG-dimonium, two-dodecyl dimethyl ammonium chloride, two-stearyl dimethyl ammonium chloride, di -tetradecyldimethylammonium chloride, di-hexadecyldimethylammonium chloride, di-stearyldimethylammonium chloride, stearamidopropylphosphoric acid chloride PG-dimonium, Stearamidopropyl ethyl dimonium ethyl sulfate, stearamidopropyl dimethyl (tetradecyl acetic acid) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium toluene sulfonate, stearamide Select from the group consisting of propyl dimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate, and mixtures thereof.

A preferred cationic surfactant can be selected from behenyl amidopropyl chloride PG-dimonium, two-dodecyl dimethyl ammonium chloride, two-stearyl dimethyl ammonium chloride, di - Selected from the group consisting of tetradecyldimethylammonium chloride, di-hexadecyldimethylammonium chloride, and mixtures thereof.

A preferred combination of cationic surfactant and structuring agent is behenyl amidopropyl PG-dimonium chloride and/or behenyl alcohol, where ratios are preferably optimized to maintain or enhance physical and chemical stability properties, especially when the combination contains ionic and/or highly polar solvents. This combination is especially useful for delivering sunscreens such as zinc oxide and octyl methoxycinnamate.

A wide variety of anionic surfactants are suitable for use in the present invention. See US Patent 3,929,678 to Laughlin et al. (issued December 30, 1975) which is incorporated herein by reference in its entirety. Non-limiting examples of anionic surfactants include alkanoyl isethionates and alkyl and alkyl ether sulfates. Generally, alkanoyl isethionate can be represented by the formula RCO-OCH ₂ CH ₂ SO ₃ M, wherein R is an alkyl or alkenyl group with about 10 to about 30 carbon atoms, and M is a water-soluble cation, such as ammonium, sodium , potassium and triethanolamine. Non-limiting examples of these isethionates include ammonium cocoyl isethionate, sodium cocoyl isethionate, sodium lauroyl isethionate, sodium stearyl isethionate, and A mixture of alkanoyl isethionates.

Alkyl sulfates and alkyl ether sulfates are generally represented by the formulas ROSO ₃ M and RO(C ₂ H ₄ O) _X SO ₃ M, where R is an alkyl or alkenyl group of about 10 to about 30 carbon atoms , x is from about 1 to about 10, M is a water-soluble cation such as ammonium, sodium, potassium and triethanolamine. Another class of suitable anionic surfactants is the water-soluble salt of the reaction product of sulfuric acid and organic matter, which has the general formula:

R ₁ -SO ₃ -M

In the formula, _R is selected from straight-chain or branched saturated aliphatic hydrocarbon groups containing about 8 to about 24, preferably about 12 to about 18 carbon atoms, and M is a cation. Other synthetic anionic surfactants include the class known as succinamates, olefin sulfonates having from about 12 to about 24 carbon atoms, and beta-alkoxyalkane sulfonates. Examples of such materials are sodium lauryl sulfate and ammonium lauryl sulfate.

Other anionic materials suitable for use herein are fatty acid soaps (ie alkali metal salts such as sodium or potassium salts) generally containing from about 8 to about 24 carbon atoms, preferably from about 10 to about 20 carbon atoms. Soap-making fatty acids can be obtained from natural sources such as glycerides obtained from plants or animals (eg, palm oil, coconut oil, soybean oil, castor oil, tallow, lard, etc.). Fatty acids can also be produced synthetically. Soaps are described in more detail in U.S. Patent 4,557,853 cited above.

Amphoteric and zwitterionic surfactants can also be used in the present invention. Examples of amphoteric and zwitterionic surfactants that can be used in the compositions of the present invention include those derivatives that can be broadly referred to as aliphatic secondary and tertiary amines, wherein the aliphatic groups may be straight or branched and one of the aliphatic The substituents contain from about 8 to about 22 carbon atoms (preferably C8-C18), one containing an anionic water-soluble group such as carboxyl, sulfonate, sulfate, phosphate or phosphonate. Examples are alkyliminoacetates and iminodialkanoates and aminoalkanoates of formula RN[(CH ₂ ) _m CO ₂ M] ₂ and RNH(CH ₂ ) _m CO ₂ M , wherein m is 1-4, R is C8-C22 alkyl or alkenyl, M is hydrogen, alkali metal, alkaline earth metal, ammonium or alkanolammonium. Derivatives of imidazolinium and ammonium are also included. Specific examples of suitable amphoteric surfactants include sodium 3-dodecyl-alanine, sodium 3-dodecylaminopropane sulfonate, N-alkyl taurine sulfonic acids, as proposed according to U.S. Patent 2,658,072 The N-alkyl taurine obtained by the reaction of dodecylamine and sodium isethionate, the content of which has been included in this article for reference; N-higher alkyl aspartic acid is manufactured according to U.S. Patent 2438091 , the contents of which are hereby incorporated by reference in their entirety, as well as products sold under the trade name "Miranol" as described in US Patent 2,528,378, which is hereby incorporated by reference in its entirety. Other suitable amphoteric surfactants include phosphates, such as cocamidopropyl PG-dimethylammonium chloride phosphate (eg, Monaquat PTC, commercially available from Mona Corporation).

Other amphoteric or zwitterionic surfactants suitable for use herein are betaines. Examples of betaines include higher alkyl betaines such as cocoyl dimethyl carboxymethyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl dimethyl alpha carboxyethyl betaine, cetyl di Methylcarboxymethylbetaine, cetyldimethylbetaine (Lonzaine 16SP from Lonza), laurylbis-(2-hydroxyethyl)carboxymethylbetaine, stearylbis-(2 -Hydroxypropyl) carboxymethyl betaine, oleyl dimethyl γ-carboxypropyl betaine, lauryl bis-(2-hydroxypropyl) α-carboxyethyl betaine, coco dimethyl sulfonate propyl betaine, stearyl dimethyl sulfopropyl betaine, lauryl dimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl) sulfopropyl betaine and amides betaine and amidosulfobetaine (wherein the RCONH(CH ₂ ) ₃ group is attached to the nitrogen atom of the betaine), oleyl betaine (VelvetexOLB-50 from Henkel) and cocamido Propyl betaine (Velvetex BK-35 and BA-35 available from Henkel).

Other suitable amphoteric and zwitterionic surfactants include sultaines and hydroxysultaines such as cocamidopropyl hydroxysultaine (Miratain CBS from Rhone-Poulenc) and the corresponding Alkanoyl N-methylglycine salts of the formula RCON(CH ₃ )CH ₂ CH ₂ CO ₂ M, wherein R is an alkyl or alkenyl group of about 10 to about 20 carbon atoms, and M is a water-soluble cation, such as Ammonium, sodium, potassium and trialkanolamines such as triethanolamine, a preferred example being sodium lauroyl N-methylglycinate.

(3) water

Preferred Oil-in-Water Emulsions The compositions of the present invention contain from about 25% to 98%, preferably from about 65% to 95%, more preferably from about 70% to 90%, by weight of the topical carrier, of water.

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

The topical compositions of the present invention, including but not limited to lotion and cream forms, may contain a dermatologically acceptable emollient. Such compositions preferably contain from about 1% to about 50% softener. As used herein, "emollients" refer to substances that are used to prevent or reduce dryness of the skin while also protecting the skin. A wide variety of suitable softeners are known for use herein. Many examples of materials suitable as emollients are described in Sagarin, Cosmetic Science and Technology, Second Edition, Vol. 1. pp. 32-43 (1972), incorporated herein by reference. A preferred emollient is glycerin. Glycerin is used in an amount of about 0.001 to about 30%, more preferably about 0.01 to 20%, still more preferably about 0.1 to about 10%, for example 5%.

Lotions and creams according to the invention generally contain a solution carrier system and one or more emollients. Lotions and creams typically contain from about 1% to about 50%, preferably from about 1% to about 20%, of emollients; from about 50% to about 90%, preferably from about 60% to about 80% of water; and the above amounts of farnesol, bisabolol and additional skin care actives. Creams are usually thicker than lotions because they contain higher levels of softeners or thickeners.

Ointments according to the invention may contain a common animal or vegetable oil or semisolid hydrocarbon (oleaginous) carrier base; absorbent ointment bases which can absorb water to form emulsions; or water-soluble carriers, such as water-soluble solution carriers. Ointments also contain thickeners, such as those described in Sagarin, Cosmetic Science and Technology, Second Edition, Vol. 1.pp.72-73 (1972), incorporated herein by reference; and/or softening agent. For example, an ointment may contain from about 2% to about 10% of an emollient; from about 0.1% to about 2% of a thickening agent; and farnesol, bisabolol and additional skin care actives in the above amounts.

There is a suitable carrier in the composition ("cleaning agent") formula for cleaning of the present invention, for example, as described above, it is preferred that in addition to containing the phytantriol and bisabolol of the above-mentioned consumption in the composition, there is also From about 1% to about 90%, more preferably from about 5% to about 10%, of a dermatologically acceptable surfactant. Suitable surfactants are selected from anionic, nonionic, zwitterionic, amphoteric and ampholytic surfactants, and mixtures of these surfactants. Such surfactants are well known to those skilled in the laundry art. Non-limiting examples of possible surfactants include isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, and sodium lauryl sulfate. Examples of surfactants useful herein are described in U.S.P. No. 4,800,197, issued January 24, 1989 to Kowez et al., which is incorporated herein by reference in its entirety. A wider variety of examples of other surfactants that may be used herein are described in McCutcheon's Detergents and Emulsifiers North American Edition (1986), Allured Publishing Company. Optionally, the cleaning composition may contain other materials conventionally used in cleaning compositions in amounts established in the art.

The physical form of the cleaning composition is not critical. The compositions can be, for example, toilet bars, body washes, shampoos, body gels, hair conditioners, hair tonics, salves, or mousses. Rinse-off cleansing compositions, such as shampoos, require a delivery system to deposit a sufficient amount of active ingredients on the skin and scalp. A preferred delivery system involves the use of insoluble complexes. For a more complete disclosure of such delivery systems, see U.S.P. 4,835,148, issued May 30, 1989 to Barford et al.

The term "foundation" as used herein refers to liquid, semi-liquid, semi-solid, or solid skin cosmetics, including, but not limited to, lotions, creams, gels, pastes, compacts, and the like. Typically foundations are applied over large areas of skin, such as the face, to provide a particular look. Foundations are typically used to provide an adherent base for colored cosmetics, such as blush, blusher, face powder and the like, to help conceal skin imperfections and provide the skin with a smooth, even appearance. The foundations of the present invention comprise a dermatologically acceptable carrier and also contain conventional ingredients such as oils, colorants, pigments, emollients, perfumes, waxes, stabilizers, and the like. For example, some exemplary carriers and other components suitable for use herein are described in PCT Application WO 96/33689, published October 31, 1996, by Canter et al., and GB2274585, issued August 3, 1994. Composition preparation method

Methods of preparation of the compositions of the present invention are generally conventional methods known in the art of preparing topical compositions. These methods generally involve mixing the ingredients into a relatively uniform state in one or more steps, with or without heating, cooling, vacuum, etc. Ways to Regulate Skin Condition

The compositions of the present invention are useful for regulating the condition of mammalian skin. Such regulation of keratinous tissue condition includes prophylactic and therapeutic regulation. For example, such methods of regulation refer to densifying keratinous tissue (i.e. structuring the epidermis and/or dermis of the skin and, where applicable, of the nails and hair shaft), and preventing and/or retarding the atrophy of mammalian skin, preventing and/or Blocks the appearance of capillaries and/or erythema on the skin of mammals, prevents and/or blocks the appearance of dark circles under the eyes, sallow complexion, sagging, softens and/or smoothes lips, hair and nails, prevents and/or Reduces itchy skin, regulates skin texture (eg wrinkles and fine lines) and improves skin tone (eg redness, freckles).

Modulating the condition of keratinous tissue generally involves administering to keratinous tissue a safe and effective amount of a composition of the present invention. The amount of application, frequency of application and duration of use will vary widely with the level of farnesol, bisabolol and additional skin care actives and/or other ingredients in a given composition and the degree of adjustment required, e.g. The extent of aging and the rate at which the skin ages further.

In a preferred embodiment, the composition is applied chronically to the skin. "Long-term topical administration" refers to the continuous application of the composition for an extended period of time in the individual's life, preferably at least about 1 week, more preferably at least about 1 month, more preferably at least about 3 months, and more preferably at least about 6 months. months, and preferably at least about 1 year. Chronic administration over the lifetime of the individual is preferred, although benefits may be obtained after various maximum periods of time, such as after five, ten or twenty years. During these periods, application is generally about once per day, but the rate of application can be from about once per week to about 3 or more times per day.

The compositions of the present invention can be used in a wide range of amounts to provide an appearance and/or sensory benefit to the skin. The composition is generally used in an amount (in milligrams of composition per square centimeter of skin) of about 0.1 mg/cm ² to about 10 mg/cm ² . In particular the amount applied is about 2 mg/cm ² .

Preferably, conditioning of keratinous tissue is effected through lotions, creams, gels, foams, ointments, pastes, lotions, sprays, conditioners, tonics, cosmetics, lipsticks, foundations, nail polishes, post-shave Conditioners or Other Preferred Forms Apply the compositions to the skin or other keratinous structures for aesthetic, preventive, therapeutic or other benefits (ie "leave-on" compositions). After applying the composition to the skin, it is preferably left on the skin for at least about 15 minutes, more preferably at least about 30 minutes, more preferably at least about 1 hour, most preferably at least about several hours, such as up to 12 hours. Can treat any part of the exterior of the face, hair and/or nails, such as face, lips, under-eye area, eyelids, scalp, neck, torso, arms, hands, legs, feet, nails, toenails, scalp hair, eyelashes, eyebrows, etc. . Compositions can be applied with the fingers or with any device such as pads, cotton balls, applicator pens, spray applicators, and the like.

Another way to ensure continued exposure of the skin to at least a minimum amount of farnesol, bisabolol and additional skin care actives is to apply the composition using a patch application to, for example, the face. This approach is especially useful for problematic areas of the skin that require more intensive treatment (such as facial creases, frown lines, under-eye area, etc.). The patch can be occlusive, semi-occlusive or non-occlusive. The combination of farnesol, bisabolol and additional skin care actives can be included in the patch or applied to the skin prior to application of the patch. The patch may also contain other actives such as chemical initiators for exothermic reactions as described in US 5,821,250; 5,981,547 and 5,972,957 to Wu et al. Preferably the patch is left on the skin for at least about 5 minutes, more preferably at least about 15 minutes, still more preferably at least about 30 minutes, still more preferably at least about 1 hour, still more preferably about overnight for an overnight treatment.

Example

The following examples will further describe and illustrate specific examples within the scope of the present invention. These embodiments are for the purpose of illustration only, and are not intended to limit the present invention, and many changes are possible without violating the spirit and scope of the present invention.

Example 1-6

A skin cream is prepared by conventional methods from the following ingredients. Element Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Phase A: Water USP Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Disodium EDTA 0.1 0.1 0.1 0.1 0.1 0.1 Methylparaben 0.25 0.25 0.25 0.25 0.25 0.25 Nicotinamide 2.0 3.5 Dexpanthenol 1.0 1.0 Allantoin 0.20 0.20 0.20 0.20 0.20 0.20 glycerin 7.0 7.0 7.0 7.0 7.0 7.0 Phase B: cetyl alcohol 0.3 0.3 0.3 0.3 0.3 0.3 stearyl alcohol 0.5 0.5 0.5 0.5 0.5 0.5 Docosanol 0.4 0.4 0.4 0.4 0.4 0.4 vitamin E acetate 0.5 0.5 Myrj 59 0.10 0.10 0.10 0.10 0.10 0.10 Propyl paraben 0.10 0.10 0.10 0.10 0.10 0.10 Farnesol 5.0 5.0 5.0 5.0 5.0 5.0 (-)-α-Bisabolol 1.0 1.0 1.0 1.0 1.0 1.0 Phytantriol 5.0 1.0 Permethyl 101A 3.3 3.0 3.0 3.0 3.0 3.0 Phase C: Sepigel 305 2.0 2.0 2.0 2.0 2.0 2.0 Phase D: Titanium dioxide GLW75CA* 0.5 Phase E: Benzyl alcohol 0.50 0.50 0.50 0.50 0.50 0.50 Dimethicone/Dimethiconol 0.50 0.50 0.50 0.50 0.50 0.50 Phase F: Palmitoyl-Lys-Thr-Thr-Lys-Ser ¹ 3.0 3.0 3.0 Phase G: spices 0.20 0.20 0.20 0.20 0.20 0.20 ¹ Peptide can be purchased from Sederma Company Matrixyl (100ppm palmitoyl-Lys-Thr-Thr-Lys-Ser) ^* purchased from KOBO Company

Mix the phase A components with a suitable mixer (such as Tekmar RW 20 DZM type), and heat to 70-80°C under stirring. Separately, mix Phase B ingredients with a suitable mixer and heat to 70-75°C with mixing and hold. Add phase B to phase A with good mixing to emulsify. When the emulsion is about 60°C, add phase C while continuing to mix the emulsion. The emulsion was cooled to about 40°C and stirred. At about 50°C, add Phase D and Phase E to the emulsion and continue mixing. At about 40°C, phase F and phase G were added to the emulsion. The emulsion was then ground for about 5 minutes with a suitable mill (Tekmar T-25) to obtain a homogeneous product.

Example 7-10

A skin lotion is prepared by conventional methods from the following ingredients. Element Example 7 Example 8 Example 9 Example 10 Phase A Water USP Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Disodium EDTA 0.10 0.10 0.10 0.10 Allantoin 0.20 0.20 0.20 0.20 glycerin 5.0 5.0 5.0 5.0 Nicotinamide 3.5 Phase B cetyl alcohol 1.2 1.2 1.2 1.2 stearyl alcohol 1.2 1.2 1.2 1.2 Brij 721 0.5 0.5 0.5 0.5 Brij 72 0.1 0.1 0.1 0.1 salicylic acid 1.5 1.5 1.5 1.5 PPG-15 stearyl ether 4.0 4.0 4.0 4.0 Farnesol 3.0 3.0 3.0 3.0 (-)-α-Bisabolol 1.0 1.0 0.5 1.0 Phytantriol Vitamin E Acetate 0.5 Titanium dioxide SAT-T-CR-50 0.5 0.50 Phase C Sepigel 305 1.0 1.0 1.0 1.0 Phase D Dimethicone/Dimethiconol 0.5 0.5 0.5 0.5 Phase E Palmitoyl-Lys-Thr-Thr-Lys-Ser ¹ 3.0 3.0 Phase F spices 0.20 0.20 0.20 0.20 ¹ The peptide can be Matrixyl (100ppm Palmitoyl-Lys-Thr-Thr-Lys-Ser) available from Sederma ^* available from US Cosmetics

Mix the phase A components with a suitable mixer (such as Tekmar RW 20 DZM type), and heat to 70-80°C under stirring. Separately, mix Phase B ingredients with a suitable mixer and heat to 70-75°C with mixing and hold. Add phase B to phase A with good mixing to emulsify. When the emulsion is about 60°C, add phase C while continuing to mix the emulsion. The emulsion was cooled to about 40°C and stirred. At about 50°C, add phase D to the emulsion and continue mixing. At about 40°C, phase E and phase F were added to the emulsion. The emulsion was then ground for about 5 minutes with a suitable mill (Tekmar T-25) to obtain a homogeneous product.

Example 12-17

A skin cream is prepared by conventional methods from the following ingredients. Element Example 12 Example 13 Example 14 Example 15 Example 16 Example 17 Phase A Water USP Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Appropriate amount to 100 Disodium EDTA 0.15 0.15 0.15 0.15 0.15 0.15 Methylparaben 0.25 0.25 0.25 0.25 0.25 0.25 Allantoin 0.20 0.20 0.20 0.20 0.20 0.20 Dexpanthenol 1.0 glycerin 3.0 3.0 3.0 3.0 3.0 3.0 Phase B cetyl alcohol 0.30 0.30 0.30 0.30 0.30 0.30 stearyl alcohol 0.50 0.50 0.50 0.50 0.50 0.50 Docosanol 0.40 0.40 0.40 0.40 0.40 0.40 Myrj 59 0.10 0.10 0.10 0.10 0.10 0.10 Propyl paraben 0.10 0.10 0.10 0.10 0.10 0.10 Farnesol 5.0 5.0 3.0 3.0 5.0 5.0 (-)-α-Bisabolol 1.0 0.5 1.0 0.5 1.0 1.0 Permethyl 101 A 3.25 3.25 3.25 3.25 3.25 3.25 Octyl Methoxycinnamate 1.5 2.0 7.0 6.0 4,4'-tert-butylmethoxydibenzoylmethane 2.0 2.0 2.0 octocrylene 5.0 1.5 Zinc oxide 3.0 Terexylylene dicampone sulfonic acid 3.0 Octyl Salicylate 4.0 Phase C Sepigel 305 2.0 2.0 2.0 2.0 2.0 2.0 Phase D Titanium dioxide GLw75CA* 0.5 0.5 0.50 Phase E Benzyl alcohol 0.50 0.50 0.50 0.50 0.50 0.50 Dimethicone/Dimethiconol 0.75 0.75 0.75 0.75 0.75 0.75 Phase F Palmitoyl-Lys-Thr-Thr-Lys-Ser ¹ 3.0 Phase G water 2.0 Finsolv TN 1.5 Polysorbate-20 0.20 retinyl propionate 0.20 Phase H spices 0.10 0.10 0.10 0.10 0.20 0.20 ¹ Peptide can be purchased from Sederma Company Matrixyl (100ppm palmitoyl-Lys-Thr-Thr-Lys-Ser) ^* purchased from KOBO Company

Mix the phase A components with a suitable mixer (such as Tekmar RW 20 DZM type), and heat to 70-80°C under stirring. Separately, mix Phase B ingredients with a suitable mixer and heat to 70-75°C with mixing and hold. Add phase B to phase A with good mixing to emulsify. When the emulsion is about 60°C, add phase C while continuing to mix the emulsion. The emulsion was cooled to about 40°C and stirred. At about 50°C, add Phase D and Phase E to the emulsion and continue mixing. At about 40°C, phases F, G and H were added to the emulsion. The emulsion was then ground for about 5 minutes with a suitable mill (Tekmar T-25) to obtain a homogeneous product.

Sequence Listing <110> L. R. Robinson

D.L. Bisset

G.E. Dekner

R.B.K. Ha <120>Skin care composition comprising a combination of skin care actives <130>Skin care composition 3<140>8023<141>2000-04-07<160>2<170>PatentIn Ver.2.1<210>1<211 >5<212>PRT<213>Artificial sequence<220><223>Description of artificial sequence:

Description of palmitoyl-lys-thr-thr-lys-ser<400>1Lys Thr Thr Lys Ser1 5<210>2<211>4<212>PRT<213>artificial sequence<220><223>artificial sequence

arg-ser-arg-lys<400>2Arg Ser Arg Lys1

Claims (10)

1. skin care compositions is characterized in that it comprises:

A) safe and effective amount, the farnesol of preferred composition weight 0.1% to 10%;

B) safe and effective amount, the bisabolol of preferred composition weight 0.1% to 10%;

C) at least a additional skin care activity thing of safe and effective amount; With

D) acceptable carrier on the Dermatology.

2. the skin care compositions of claim 1 also wherein adds the skin care activity thing and is selected from: decortication bits active matter, anti-acne active matter, vitamin B ₃Chemical compound, retinoid, peptide, hydroxy acid, antioxidant, radical scavenger, chelating agen, anti-inflammatory agent, local anesthetic, suntan, skin whitener, anti-cellulite knit agent, flavonoid, anti-microbial active, comfortable dose of skin, skin healing agent, antifungal, sunscreen actives thing, conditioner, structural reagent, thickening agent, and composition thereof.

3. the skin care compositions of claim 1, wherein additional skin care activity thing is a phytantriol.

4. claim 1 or 3 skin care compositions, wherein additional skin care activity thing is selected from vitamin B ₃Chemical compound and composition thereof, preferably additional skin care activity thing is a nicotiamide.

5. the skin care compositions of claim 1,3 or 4, wherein additional skin care activity thing is a salicylic acid.

6. claim 1; 3; 4 or 5 skin care compositions, wherein additional skin care activity thing is to be selected from following peptide active matter: lys-thr-thr-lys-ser, gly-his-lys; beta-ala-his; arg-ser-arg-lys, arg-lys-arg, his-gly-gly; its derivant and composition thereof, preferred peptide derivant are palmityl-lys-thr-thr-lys-ser.

7. the skin care compositions of claim 1, wherein additional skin care activity thing is nicotiamide, Tocopherol acetate ester and dexpanthenol.

8. claim 1 or 2 skin care compositions, wherein additional skin care activity thing is to comprise the inorganic sunscreen actives thing that is selected from following metal-oxide: average initial particle is the titanium dioxide of about 15nm to about 100nm, average initial particle is the zinc oxide of about 15nm to about 150nm, average initial particle is the zirconium oxide of about 15nm to about 150nm, average initial particle is the ferrum oxide of about 15nm to about 500nm, and composition thereof.

9. claim 1 or 2 compositions, wherein additional skin care activity thing is to be selected from following organic sunscreen active matter: octyl methoxycinnamate, ethylhexyl salicylate, terephthalylidene dicamphor sulfonic acid, avobenzone, octocrilene, and composition thereof.

10. the skin care compositions of above-mentioned each claim is in the application of preparation in the medicine, and this medicine is by being used to regulate the mammalian skin situation on the skin that is locally applied to mammal and need handles.