MXPA00009144A - Compositions for regulating skin appearance - Google Patents

Abstract

The present invention relates to compositions for preventing or treating skin disorders using vitamin B3 compounds and polycyclic compounds. The present invention also relates to methods for regulating skin condition.

Description

COMPOSITIONS TO REGULATE THE APPEARANCE OF THE SKIN TECHNICAL FIELD The present invention relates to compositions for preventing or treating skin disorders using vitamin B3 compounds and polycyclic compounds. The present invention also relates to methods for regulating skin conditions.

BACKGROUND OF THE INVENTION Many personal care products currently available to consumers are primarily aimed at improving the health and / or physical appearance of the skin. Among these skin care products, many are aimed at delaying, minimizing or even eliminating wrinkling of the skin and other histological changes typically associated with aging of the skin or environmental damage to human skin. Other types of products are useful for imparting moisturization to dry skin, providing sun protection to skin exposed to sunlight, and causing the desired control of pigmentation, especially the lightening of darkened or hyperpigmented skin. The skin is subjected to aggression by many extrinsic and intrinsic factors. Extrinsic factors include ultraviolet radiation (for example, from sun exposure), environmental pollution, wind, heat or infrared (IR) radiation, low humidity, aggressive surfactants, abrasives and the like, intrinsic factors include chronological aging and other biochemical changes from inside the skin. Whether extrinsic or intrinsic, these factors result in visible signs of skin aging and environmental damage, such as wrinkling and other forms of roughness (including increased pore size, scaling and skin lines), and other associated histological changes with aging or skin damage. For many people, wrinkles on the skin are a reminder of the disappearance of youth. As a result, the elimination of wrinkles has become a latent business in the conscious societies of youth. The treatments vary from cosmetic creams and moisturizers to various forms of cosmetic surgery. Extrinsic or intrinsic factors can result in thinning and general degradation of the skin. For example, as the skin ages naturally, there is a reduction in the cells and blood vessels that supply the skin. There is also a flattening of the dermal-epidermal junction which results in a weaker mechanical strength of this joint. See, for example, Oikarinen, "The Aging of Skin: Chronoaging Versus Photoaging," Photodermatol. Photoimmunol. Photomed., Vol. 7, pp. 3-4, 1990, which is incorporated herein by reference in its entirety.

It has now been found that topical compositions containing a vitamin B3 compound and selected polycyclic compounds provide benefits for regulating the condition of the skin previously not recognized in the art of which the present inventors are aware. For example, said compositions regulate signs of skin aging, especially visible and / or tactile discontinuities in the skin texture associated with aged skin, including fine lines and wrinkles. Therefore, an object of the present invention is to provide topical compositions for prophylactically and / or therapeutically regulating the skin condition of mammals (especially human skin, most especially facial skin), which contain a vitamin B3 compound and a polycyclic compound . Another objective of the present invention is to provide topical compositions for prophylactically and / or therapeutically regulating aging signals in mammalian skin, which contain a vitamin B3 compound and a polycyclic compound. A further object of the present invention is to provide compositions for prophylactically and / or therapeutically regulating visible and / or tactile discontinuities in mammalian skin texture, including fine lines, wrinkles, enlarged pores, roughness, dryness and other texture discontinuities. The skin associated with aging thereof, which contain a compound of vitamin B3 and a polycyclic compound.

The present invention also relates to methods for providing such regulation using the present compositions. These and other objects of this invention will become apparent in the light of the following description.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to topical compositions comprising: a) a safe and effective amount of a vitamin compound B3; b) a safe and effective amount of a polycyclic compound selected from the group consisting of: i) flavanones selected from the group consisting of unsubstituted flavanones, monosubstituted flavonones and mixtures thereof; ii) chalcones selected from the group consisting of unsubstituted chalcones, monosubstituted chalcones, disubstituted chalcones, trisubstituted chalcones and mixtures thereof; iii) flavones selected from the group consisting of unsubstituted flavones, monosubstituted flavones, disubstituted flavones and mixtures thereof; V) one or more soflavones; v) coumarins selected from the group consisting of unsubstituted coumarins, monosubstituted coumarins, disubstituted coumarins and mixtures thereof; vi) chromones selected from the group consisting of unsubstituted chromones, monosubstituted chromones, disubstituted chromones and mixtures thereof; vii) one or more dicumaroles; viii) one or more chromanones; ix) one or more chromanols; x) sterols selected from the group consisting of stigmasterol, stigmastanol, brasicasterol, campesterol and mixtures thereof; xi) triterpenoids selected from the group consisting of betulinic acid, boswellic acid and mixtures thereof; and xii) mixtures thereof; c) and a dermatologically acceptable vehicle for the vitamin B3 compound and the polycyclic compound. The present invention also relates further to methods for treating and regulating the condition of the skin using the topical compositions.

DETAILED DESCRIPTION OF THE INVENTION All percentages and ratios used herein are by weight of the total composition and all measurements are made at 25 ° C unless otherwise indicated. The compositions of the present invention may comprise, consist essentially of, or consist of, the essential as well as optional ingredients and components described herein. As used herein, "consisting essentially of" means that the composition or component may include additional ingredients, but only if the additional ingredients do not materially alter the basic and novel characteristics of the claimed compositions or methods. All publications cited herein are therefore incorporated by reference in their entirety. The term "topical application", as used herein, means applying or spreading the compositions of the present invention on the surface of the skin. The term "dermatologically acceptable", as used herein, means that the compositions or components thereof described in this manner are suitable for use in contact with human skin without undue toxicity, incompatibility, instability, allergic response and the like.

The term "safe and effective amount", as used herein, means an amount of a compound or composition sufficient to induce significantly a positive benefit, preferably a positive benefit of sensation and appearance of the skin, independently including the benefits described. in the present, but low enough to avoid serious side effects, that is, to provide a benefit ratio at reasonable risk, within the scope of the fair judgment of the person skilled in the art. The compositions of the present invention are useful for topical application and for regulating skin conditions, including visible and / or tactile discontinuities in the skin (especially the surface of the skin, said discontinuities being generally undesirable). Such discontinuities can be induced or caused by internal and / or external factors, and include the signs of skin aging described herein. "Regulating the condition of the skin" includes prophylactically and / or therapeutically regulating the condition of the skin, including visible and / or tactile discontinuities in the skin, such as, but not limited to, regulating visible and / or tactile discontinuities in the texture of the skin, reduce postinflammatory hyperpigmentation, reduce the non-melaninous discoloration of the skin, regulate the moisturizing and barrier properties of the skin, regulate skin epidermal differentiation, regulate the exfoliation of the skin, thicken the skin to reduce atrophy in skin, regulate the elasticity of the skin, reduce oily skin, regulate cellulite on skin, regular pruritus on the skin, promote the healing of wounds on the skin, protect the skin from environmental aggressiveness and regulate inflammation of the skin. As used herein, prophylactically regulating the condition of the skin includes delaying, minimizing and / or avoiding visible and / or tactile discontinuities in the skin. As used herein, therapeutically regulating the condition of the skin includes decreasing, for example, reducing, minimizing and / or covering skin discontinuities. Regulating skin conditions does not include improving the appearance and / or sensation of the skin. The compositions of the present invention are useful for regulating signs of skin aging, more specifically visible and / or tactile discontinuities in the skin texture associated with aging. "Regulating signs of skin aging" includes prophylactically and / or therapeutically regulating one or more of said signals (similarly, regulating certain signs of aging of the skin, for example, lines, wrinkles or pores, including prophylactically regulating and / or therapeutically regulate that signal). As used herein, prophylactically regulating said signals includes delaying, minimizing and / or preventing signs of skin aging. As used herein, therapeutically regulating said signals includes decreasing, for example, reducing, minimizing and / or covering signs of skin aging. "Signs of skin aging" includes, but is not limited to, all externally visible and tactilely perceptible manifestations, as well as any other macro or micro effect due to the aging of the skin. Such signals can be induced or caused by intrinsic factors or extrinsic factors, for example, chronological aging and / or environmental aggression (eg, sunlight, UV, smoke, ozone, pollutants, stress, etc.). These signals may be the result of processes that include, but are not limited to, the development of texture discontinuities such as wrinkles, including both fine surface wrinkles and deep deep wrinkles, lines on the skin, lines by facial puckering, fine lines , rhytidosis, dermatoheliosis, light damage, premature aging of the skin, folds, edges, pitting, large pores, pimples (for example, associated with attached structures such as sweat gland ducts, sebaceous glands or hair follicles), appearance of skin type "orange peel", dryness, scaly, and / or other forms of disuniformity or roughness of the skin; rashes such as acne, pimples, ruptures; problems of excess fat on the skin such as overproduction of sebum, fattyness, facial shine, breaking of the foundations; abnormal desquamation (or exfoliation) or abnormal epidermal differentiation (eg, abnormal skin disease) such as scaly, dry, keratoses, hyperkeratinization; moisturization (or hydration) of inadequate skin such as that caused by damage to the skin barrier, environmental dryness; loss of skin elasticity (loss and / or inactivation of the functional elastin of the skin) such as elastosis, inflammation (including swelling of the eye area and dark circles), loss of skin firmness, loss of stiffness of the skin, loss of recovery of the skin from the deformation; Discoloration of the non-melaninous skin such as (including circles under the eye), redness (eg, non-uniform pigmentation or redness due to, for example, rosacea), pallor (pale color), discoloration caused by telangiectasia or spider vessels; hyperpigmented skin regions related to melanin (or unevenly pigmented) such as age spots (liver spots, brown spots) and freckles; post-inflammatory hyperpigmentation such as occurs after an inflammatory event (eg, as an acne lesion, buried hair, insect / spider bite or sting, rayon, cut, wound, abrasion and the like); and atrophy such as, but not limited to, that associated with aging or use of spheroids; other histological or microscopic alterations in the skin components such as terrestrial substances (for example, hyaluronic acid, glycosaminoglycans, etc.); collagen degradation and alterations or structural abnormalities (for example, changes in the stratum corneum, dermis, epidermis, the vascular system of the skin such as telangiectasia or spider vessels); tissue responses to assions such as itching or pruritus; and alterations to underlying tissues (eg, subcutaneous fat, cellulitis, muscles, trabeculae, septa and the like), especially those close to the skin. It is to be understood that the present invention will not be limited to the regulation of the aforementioned "skin aging signals" that originate due to mechanisms associated with skin aging, but is designed to include the regulation of said signals without import the source mechanism. As used herein, "regulating the condition of the skin" is designed to include the regulation of said signals regardless of the mechanism of origin. The present invention is especially useful for therapeutically regulating visible and / or tactile discontinuities in mammalian skin texture, including texture discontinuities associated with skin aging. As used herein, therapeutically regulating said discontinuities includes decreasing, for example, reducing, minimizing and / or covering visible and / or tactile discontinuities in the mammalian skin texture, to thereby provide an appearance and / or sensation of improved skin, for example, a smoother and more uniform appearance and / or feel. Said visible and / or tactile discontinuities in the texture of the skin include folds, bumps, pores, fine lines, wrinkles, scales and / or other forms of disuniformity or roughness in texture associated with the aging of the skin. For example, the length, depth and / or other dimension of lines and / or wrinkles are decreased, the apparent diameter of the pores decreases or the apparent height of the tissue immediately close to the openings of the pores approaches that of the intra-annexed skin. . The present invention is also especially useful for prophylactically regulating visible and / or tactile discontinuities in mammalian skin texture, including texture discontinuities associated with skin aging. As used in the present, prophylactically regulating said discontinuities includes delaying, minimizing and / or preventing visible and / or tactile discontinuities in the texture of mammalian skin, to then provide an improved appearance and / or skin feel, eg, an appearance and / or sensation of smoother and more uniform skin. The compositions of the present invention are also useful for promoting exfoliation or scaling or regeneration of the skin. Without wishing to be bound by theory, it is believed that compositions containing the vitamin B3 compound, particularly niacinamide, reinforce the energy state of the cells that regulate exfoliation, resulting in the normalization of epidemic differentiation, keratinization and regeneration. The compositions of the present invention are also useful for moisturizing the skin. Without intending to be limited or reduced by theory, it is believed that compositions containing the vitamin B3 compound, particularly niacinamide and / or tocopherol nicotinate, increase skin wetting or hydration by various different mechanisms. One mechanism includes the effect of vitamin B3 compounds on natural wetting factors. Natural wetting factors include the agglutination of water, metabolic byproducts of skin proteins, especially filagñna. It is believed that vitamin B3 compounds increase the level of skin proteins mentioned above, thereby increasing the level of natural wetting factors and, thus, wetting. Another mechanism includes the effect of the vitamin B3 compounds on the level and / or molecular weight of the keratin proteins in the stratum corneum. These proteins agglutinate water and help provide flexibility to the layer of cells of the stratum corneum. Therefore, an increased keratin level increases the concentration of moisture agglutination proteins, resulting in improved skin wetting. The degree of skin moistening obtained, or flexibility of the stratum corneum achieved as a result of hydration is also related to the type of keratin present. The layers of mature stratum corneum cells contain keratin proteins of higher molecular weight than those found in the viable epidermal cell layers. These higher molecular weight keratins (for example, keratins having a molecular weight of about 67,000) tend to bind more water and / or provide greater flexibility to the stratum corneum. It is believed that the vitamin B3 compounds stimulate the production of this higher molecular weight keratin. A third mechanism includes the effect of vitamin B3 compounds on the level of volvolume and desmosomal proteins. Invoiucrina is a protein precursor to the envelope of stratum corneum cells that encloses keratin proteins and natural wetting factors. The desmosomal proteins are in close association with the envelope of the cells of the stratum corneum and help to connect the cells of the stratum corneum. Vitamin B3 compounds increase the level of involucrin and desmosomal proteins. The increased levels of olumbucin and desmosomal protein increase and reinforce the corneal cell envelope, helping to delay the dehydration of the enclosed keratins and natural wetting factors and, therefore, improving skin moisturization. The compositions of the present invention, including the essential and optional components thereof, are described in detail hereinafter.

Essential components Component of vitamin Bg The compositions of the present invention comprise a safe and effective amount of a natural or synthetic vitamin B3 compound. The compositions of the present invention preferably include from about 0.01% to about 50%, most preferably from about 0.1% to about 40%, more preferably from about 1% to about 20%, and even more preferably from about 1% to about 10%. %, more preferably from about 1% to about 5% of the vitamin B3 compound. As used herein, "vitamin B3 compound" means a compound having the formula: wherein R is -CONH2 (ie, niacinamide), -COOH (ie, nicotinic acid) or -CH2OH (i.e., nicotinic alcohol); derivatives thereof and salts of any of the foregoing.

Examples of derivatives of the above vitamin B3 compounds include nicotinic acid esters, which include non-vasodilating esters of nicotinic acid, nicotinic amino acids, nicotinic alcohol esters and carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide . Suitable nicotinic acid esters include nicotinic acid esters with C?-C22 alco alcohols, preferably C C-C? 6, most preferred C?-C6 alcohols. The alcohols are appropriately straight chains or branched chains, cyclic or acyclic, saturated or unsaturated (including aromatic), and substituted or unsubstituted. The esters of preference are non-vasodilators. As used herein, "non-vasodilator" means that the ester commonly does not provide a visible reddening response after application to the skin in the present compositions (the majority of the general population does not experience a visible response of redness). , although such compounds can cause vasodilation not visible to the naked eye). Alternatively, a nicotinic acid material that is vasodilator at higher doses would be used at a lower dose at which the redness response would not occur. Non-vasodilating esters of nicotinic acid include tocopherol nicotinate and nositol hexanicotinate; tocopherol nicotinate is preferred. Other derivatives of the vitamin B3 compounds are niacinamide derivatives that result from the substitution of one or more of the hydrogens of the amide group. Non-limiting examples of niacinamide derivatives useful herein include nicotinyl amino acids, derived for example, from the reaction of an activated nicotinic acid (e.g., nicotinic acid azide or nicotinyl chloride) with an amino acid, and esters of nicotinic alcohol of organic carboxylic acids (for example C? -C? 8). Specific examples of such derivatives include nicotinuric acid and nicotinyl hydroxamic acid, which have the following chemical structures: nicotinuric acid: Nicotinylhydroxamic acid: Examples of nicotinyl alcohol esters include nicotinyl alcohol esters of salicylic, acetic, glycolic, palmitic carboxylic acids and the like. Other non-limiting examples of vitamin B3 compounds useful herein are 2-chloronicotinamide, 6-aminonicotinamide, 6-methylnicotinamide, n-methyl-nicotinamide, n-diethylnicotinamide, n- (hydroxymethyl) -nicotinamide, quinoline acid measure, nicotinanilide, n-benzylnicotinamide, n-ethylnicotinamide, nifenazone, nicotinaldehyde, isonicotinic acid, methylisonicotinic acid, thionicotinamide, nialamide, 1- (3-pyridylmethyl) urea, 2-mercaptonicotinic acid, nicomol, and niaprazine.

Examples of the above vitamin B3 compounds are well known in the art and are commercially available from various sources for example, Sigma Chemical Company (St. Louis, MO); ICN Biomedicals, Inc. (Irvin, CA) and Aldrich Chemical Company (Milwaukee, Wl). At present one or more vitamin B3 compounds can be used. The preferred vitamin B3 compounds are niacinamide and tocopherol nicotinate. Niacinamide is the most preferred. When they are used, the salts, derivatives and derivatives of niacinamide salts are preferably those which have substantially the same efficacy as niacinamide in the methods of regulation of the skin conditions described herein. Salts of vitamin B3 compounds may also be useful herein. Non-limiting examples of salts of vitamin B3 compounds useful herein include organic or inorganic salts, such as inorganic salts with anionic inorganic species (e.g., chloride, bromide, iodide, carbonate, preferably chloride), and carboxylic acid salts organic (including carboxylic acid salts of C 1 -C-is mono-, di- and tri-, for example, acetate, salicylate, glycolate, lactate, malate, citrate, preferably salts of monocarboxylic acid such as acetate). These and other salts of the vitamin B3 compound can be readily prepared by the person skilled in the art, for example as described by W. Wenner, "The Reaction of L-Ascorbic and D-losascorbic Acid with Nicotinic Acid and Its Amide ", J. Organic Chemistry. VOL. 14, 22-26 (1949), which is incorporated herein by reference. Wenner describes the synthesis of the ascorbic acid salt of niacinamide. In a preferred embodiment, the ring nitrogen of vitamin B3 compound is substantially chemically free, (eg, unbound and / or unimpeded), or after supplying it to the skin it becomes substantially chemically free ("chemically free" is hereinafter alternatively referred to as "not complexed"). More preferably, the vitamin B3 compound is not essentially complexed. Therefore, if the composition contains the vitamin B3 compound in the form of a salt or otherwise is in complexed form, preferably such a complex is substantially reversible, more preferably essentially reversible in supplying the composition to the skin. For example, such a complex must be substantially reversible at a pH ranging from 5.0 to 6.0. Such reversibility can easily be determined by one skilled in the art. More preferably the vitamin B3 compound is substantially not complexed in the composition prior to delivery to the skin. Examples of proposals to minimize or prevent the formation of undesired complexes include the omission of materials which form substantially irreversible complexes or other complexes with the vitamin B3 compound, the pH adjustment, the adjustment of the ionic strength, the use of agents surfactants and the formulation wherein the vitamin B3 compound and the materials that are complexed therewith are in different phases. Such proposals are within the level of ordinary skill in the art. Therefore, in a preferred embodiment, the vitamin B3 compound contains a limited amount of the salt form and is preferably substantially free of salts of a vitamin B3 compound. Preferably the vitamin B3 compound contains less than 50% of said salt, and preferably is essentially free of the salt form. The vitamin B3 compound in compositions having a pH ranging from 4 to 7 typically contains less than 50% of the salt form. The vitamin B3 compound may be included as the substantially pure material, or as an extract obtained by physical and / or chemical isolation from natural sources (eg plants). The vitamin B3 compound is preferably substantially pure, preferably essentially pure.

Polycyclic Compounds Also essential for the compositions of the present invention is a polycyclic compound selected from the group consisting of selected falvonoids, triterpenoids (also known as saponins), sterols, and mixtures thereof. Flavonoids are widely described in US Patents 5,686,082 and 5,686,367 both of which are incorporated herein by reference. Flavonoids suitable for use in the present invention are flavanones selected from the group consisting of unsubstituted flavanones, monosubstituted flavanones and mixtures thereof; chalcones selected from the group consisting of unsubstituted chalcones, monosubstituted chalcones, disubstituted chalcones, trisubstituted chalcones and mixtures thereof; flavones selected from the group consisting of unsubstituted flavones, monosubstituted flavones, disubstituted flavones and mixtures thereof; one or more soflavones; coumarins selected from the group consisting of unsubstituted coumarins, monosubstituted coumarins, disubstituted coumarins and mixtures thereof; chromones selected from the group consisting of unsubstituted chromones, monosubstituted chromones, disubstituted chromones and mixtures thereof; one or more dicumaroles; one or more chromanones; one or more chromanols; isomers (for example cis / trans isomers) thereof; and mixtures thereof. With the term "substituted" as used herein, it is intended to mean flavononoids in which one or more hydrogen atoms of the flavonium have been independently replaced with hydroxyl, C 1 -C 8 alkyl, C 1 -C 4 alkoxy, O-glucoside and the like, or a mixture of these substituents. Examples of suitable flavonoids include, but are not limited to, unsubstituted flavanone, monohydroxyflavanones (eg, 2'-hydroxy flavanone, 6-hydroxy flavanone, 7-hydroxy flavanone, etc.), mono-alkoxy flavanone (e.g. -methoxy flavanone, 6-methoxy flavanone, 7-methoxy flavanone, 4'-methoxy flavanone, etc.), unsubstituted chalcone (especially unsubstituted trans-chalcone), mono-hydroxy chalcones (eg, 2'-hydroxy chalcone, 4) '- hydroxy chalcone, etc.), di-hydroxy chalcones (eg, 2,4'-dihydroxy chalcone, 2', 4'-dihydroxy chalcone, 2,2'-dihydroxy chalcone, 2 ', 3-dihydroxy chalcone, 2' , 5'-dihydroxy chalcone, etc.) and tri-hydroxy chalcones (eg, 2 ', 3', 4'-trihydroxy chalcone, 4,2 ', 4'-trihydroxy chalcone, 2,2', 4'- trihydroxy chalcone, etc.), unsubstituted flavone, 7,2'-dihydroxy flavone, 3 ', 4'-dihydroxy naphthoflavone, 4'-hydroxy flavone, 5,6-benzoflavone and 7,8-benzoflavone, unsubstituted isoflavone, diadzein (7,4'-dihydroxy isoflavone), 5,7-dihydroxy-4'-methoxy isoflavone, soflavones of soybean (a mixture extracted from soybean), unsubstituted coumarin, 4-hydroxy coumarin, 7-hydroxy coumarin, 6-hydroxy-4-methyl coumarin, unsubstituted chromonone, 3-formyl chromone, 3-formyl-6-isopropyl chromone , unsubstituted dicoumarol, unsubstituted chromanone, unsubstituted chromanol and mixtures thereof. It is preferred to use in the present substituted flavanone, methoxy flavanones, unsubstituted chalcone, 2 ', 4-dihydroxy chalcone and mixtures thereof. More unsubstituted flavanone, unsubstituted chalcone (especially the trans isomer) and mixtures thereof are preferred. They can be synthetic materials or obtained as extracts from natural sources (for example, plants). The naturally obtained material can also be derived more (for example, an ester derivative or ether prepared after extraction from a natural source). Mixtures of the above flavonoid compounds can also be used. Triterpenoids useful herein are also well known in the art and are described in US Patents: 5,679,828; 5,643,884; ,629,351; 5,529,769 and 5,064,823, all of which are incorporated herein by reference. Preferred triterpenoids include betulinic acid, boswellic acid and mixtures thereof. The sterols useful in the present invention are described in the U.S. Patents. 5,665,366; 4,883,659 and 4,224,319, all of which are incorporated herein by reference. Preferred esterals include stigmastanol, stigmasterol, brasicasterol, campesterol and mixtures thereof. Mixtures of the above polycyclic compounds can also be used. The polycyclic compounds described herein are preferably present in this invention at concentrations of from about 0.01% to about 20%, most preferably from about 0.1% to about 10% and more preferably from about 0.1% to about 5%. The polycyclic compounds useful herein are commercially available from a number of sources, for example, Indofine Chemical Company, Inc. (Somerville, New Jersey), Steraloids, Inc. (Wilton, New Hampshire) and Aldrich Chemical Company, Inc. ( Milwaukee, Wisconsin).

Vehicle Another essential ingredient of the present invention is a dermatologically acceptable vehicle. The phrase "dermatologically acceptable vehicle", as used herein, means that the vehicle is suitable for topical application to the skin, has suitable aesthetic properties, is compatible with the active ingredients of the present invention and with any other component, and will not cause any safety or toxicity concerns. A safe and effective amount of a vehicle is from about 50% to about 99.99%, preferably from about 99.9% to about 80%, most preferably from about 98% to about 90%, more preferably from about 95% to about 90% of the composition. The vehicle can have a wide variety of forms. For example, emulsion vehicles, including, but not limited to, oil in water emulsions, water in oil, water in oil in water, and oil in water in silicone are useful herein. These emulsions can cover a wide range of viscosities, for example, from about 100 cps to about 200,000 cps. These emulsions can also be supplied in the form of sprays using either mechanical pumping containers or pressurized aerosol containers using conventional propellants. These vehicles can also be supplied in the form of a mousse. Other suitable topical vehicles include anhydrous liquid solvents such as oils, alcohols and silicones (e.g., mineral oil, ethanol, isopropanol, dimethicone, cyclomethicone and the like); individual water-based liquid phase solvents (eg, hydro-alcoholic solvent systems) and thickened versions of these anhydrous and water-based individual phase solvents (eg, where the viscosity of the solvent has been increased to form a solid or semi-solid by the addition of gums, resins, waxes, polymers, suitable salts and the like). Examples of topical vehicle systems useful in the present invention are described in the following four references, all of which are hereby incorporated by reference in their entirety: "Sun Products Formulary" Cosmetics & Toiletries, vol. 105, pp. 122-139 (December 1990); "Sun Products formulary", Cosmetics & Toiletries, vol. 102, pp. 117-136 (March 1987); patent of E.U.A. No. 4,960,764 to Figueroa et al., Issued October 2, 1990 and patent of E.U.A. No. 4,254,105 to Fukuda et al, issued March 3, 1981. The vehicles of the present invention may comprise from about 50% to about 99% by weight of the compositions of the present invention, preferably from about 75% to about 99. % and more preferably around 85% to about 95%. Preferred cosmetic and / or pharmaceutically acceptable topical vehicles include hydro-alcoholic systems and oil-in-water emulsions. When the vehicle is a hydro-alcoholic system, the vehicle may comprise about 0% to about 99% ethanol, isopropanol or mixtures thereof, and about 1% to about 99% water. More preferred is a vehicle comprising about 5% to about 60% ethanol, isopropanol or mixtures thereof, and about 40% to about 95% water. Especially preferred is a vehicle comprising about 20% to about 50% ethanol, isopropanol or mixtures thereof, and about 50% to about 80% water. When the vehicle is an oil-in-water emulsion, the vehicle can include any of the common excipient ingredients for preparing these emulsions. A more detailed description of suitable vehicles is found in the US patent. 5,605,894 to Blank et al., And in the patent of E.U.A. 5,681, 852 to Bissett, both of which are incorporated herein by reference in their entirety.

Optional components The skin regulatory compositions of the present invention may optionally comprise additional skin actives. Non-limiting examples of said active ingredients for skin include hydroxy acids such as salicylic acid; exfoliating or peeling agents such as zwitterionic surfactants; sunscreens such as 2-ethylhexyl p-methoxycinnamate, 4,4'-t-butyl methoxydibenzoyl-methane, octocrylene, phenylbenzimidazole sulfonic acid; sun blockers such as zinc oxide and titanium dioxide; anti-inflammatory agents, antioxidants / radical scavengers such as tocopherol and esters thereof; metal chelators, especially iron chelators; retinoids such as retinol, retinyl palmitate, retinyl acetate, retinyl propionate and retinal; N-acetyl-L-cysteine and derivatives thereof; hydroxy acids such as glycolic acid; keto acids such as pyruvic acid; benzofuran derivatives; depilatory agents (e.g., sulfhydryl compounds); skin lightening agents (for example arbutin, kojic acid, hydroquinone, ascorbic acid and derivatives such as ascorbyl phosphate salts, placenta extract and the like); anti-cellulite agents (for example, caffeine and theophylline); wetting agents; antimicrobial agents; antiandrogens and skin protectors. Mixtures of any of the active ingredients for skin mentioned above can also be used. A more detailed description of these assets is found in the patent of E.U.A. 5,605,894 to Blank et al (previously incorporated by reference). Preferred skin actives include hydroxy acids such as salicylic acid, sunscreens, antioxidants and mixtures thereof. Other conventional skin care product additives may also be included in the compositions of the present invention. For example, urea, guanidine, glycerol, petrolatum, mineral oil, sugar esters and polyesters, polyolefins, methyl isostearate, ethyl isostearate, cetyl ricinoleate, isononyl isononanoate, isohexadecane, lanolin, lanolin esters, cholesterol, carboxylic acid. pyrrolidone salt (PCA), trimethylglycine (betaine), tranexamic acid, amino acids (for example, serine, alanine, threonine, histidine) and / or its salts, panthenol and its derivatives, collagen, hyaluronic acid, elastin, hydrolysates, oil rose, jojoba oil, epidermal growth factor, soy saponins, mucopolysaccharides and mixtures thereof. Other suitable skin additives or active ingredients are described in greater detail in PCT application WO 97/39733, published October 30, 1997, to Oblong et al., And incorporated herein by reference in its entirety.

Preparation of the compositions The compositions of the present invention are generally prepared by conventional methods such as those known in the art of making topical compositions. Such methods typically include mixing the ingredients in one or more steps to a relatively uniform state, with or without heating, cooling, applying vacuum and the like.

Methods for regulating the condition of the skin The compositions of the present invention are useful for regulating the skin condition of mammals (especially human skin, most especially facial human skin), including visible and / or tactile discontinuities in the skin, signs of skin aging and visible and / or tactile discontinuities in the skin associated with skin aging (including fine lines, wrinkles, large pores, roughness of surface, dryness and other discontinuities in texture associated with aging skin). Said regulation includes prophylactic and therapeutic regulation. The regulation of the condition of the skin does not apply topically to the skin a safe and effective amount of a composition of the present invention. The amount of the composition to be applied, the frequency of application and the period of use will vary widely depending on the level of the vitamin B3 compound and / or the other components of a certain composition, and the level of regulation desired, for example. , based on the level of aging of the skin that is present in the subject and the speed of additional skin aging. In a preferred embodiment, the composition is chronically applied to the skin. By "chronic topical application" is meant continuous topical application of the composition over an extended period during the subject's life, preferably for a period of at least about one week, most preferably for a period of at least about one month , still very preferably about three months, even very preferably at least about six months and more preferably still at least about one year. Although the benefits can be obtained after several periods of maximum use (for example, five, ten or twenty years), it is preferred that the chronic application continue throughout the life of the subject. Applications will typically be in the order of approximately once a day during such extended periods, however application rates may vary from approximately once a week to approximately three times a day or more. A wide range of amounts of the compositions of the present invention can be employed to provide a benefit of skin appearance and / or sensation. The amounts of the present compositions that are typically applied per application are, in milligrams of composition per square centimeter of skin, about 0.1 mg / cm2 to about 10 mg / cm2. A particularly useful application amount is approximately 2 mg / cm2. The regulation of the skin condition is preferably carried out by applying the composition in the form of a lotion, cream, gel, emulsion, spray, conditioner, cosmetic, lipstick, base, nail varnish or the like which is designed to be left on the skin for some time for some aesthetic, prophylactic, therapeutic or other benefit (ie, a "non-rinseable" composition). After applying the composition to the skin, it is preferably left on the skin for a period of at least about 15 minutes, most preferably at least about 30 minutes, even most preferably at least about one hour, more preferably by at least for several hours, for example, up to about 12 hours. Any part of the outer portion of the face, hair and / or nails can be treated, for example, face, lips, eyelids, scalp, neck, torso, arms, hands, legs, nails, toenails, eyelashes, eyebrows , etc. Another approach to ensuring continuous exposure of the skin to at least a minimum level of vitamin B3 compound is to apply the compound by the use of a patch applied, for example, to the face. This approach is particularly useful for problematic areas of the skin that require more intensive treatment. The patch may be obstructive, semi-obstructive or non-obstructive. The composition with vitamin B3 compound can be contained in the patch or applied to the skin before the application of the patch. The patch may also include additional active agents such as chemical initiators for exothermic reactions such as those described in the PCT application WO 9701313 to Burkett et al. The patch is preferably left on the skin for a period of at least about 15 minutes, most preferably at least about 30 minutes, still more preferably at least about 1 hour, most preferably overnight as a form of therapy night EXAMPLES The following examples describe and demonstrate more embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration and should not be considered as limitations of the present invention, since many variations thereto are possible without departing from the spirit and scope thereof.

EXAMPLE 1 A skin cream is prepared by conventional methods from the following components.

The components of phase A are mixed with a suitable mixer (for example, Tekmar model RW20DZM), heating while stirring at a temperature of 70-80 ° C. Separately, the components of phase B are mixed with a suitable mixer and heated with mixing to melt the components. Separately, the components of phase C are mixed and ground to obtain an acceptably mild mixture (for example, using a Tekmar T50 mill). The mixture of phase C is added to the mixture of phase B and mixed together. The resulting mixture is then added to the mixture of phase A with mixing, cooled with a cold water bath and milled, and then stirring is continued. A combination of the bath is removed, with continuous agitation, once the temperature reaches 40 ° C. The components of phase D are mixed separately by stirring until they dissolve, and then added to the combination of the materials of phases A-C. The components of phase E are mixed separately by mixing until they are uniform and continuous, and then this is added to the combination of the materials of phases A-D. The fragrance is added and mixed, then the NaOH. The pH is adjusted as necessary to 5.5. The composition is applied to the wrinkled, aged or damaged facial skin of a subject in the amount of 2 mg of composition / cm2 of skin once or twice a day for a period of at least 3-6 months to reduce Fine lines and wrinkles and improve the texture of the skin surface. Alternatively, the 2 ', 4-dihydroxy chalcone can be replaced with an equivalent amount of another polycyclic compound (eg, another chalcone, flavanone, isoflavone, coumarin, flavone, chromone, dicumarol, chromanone, chromanol, triterpenoid (e.g. betulinic acid), sterol (for example, stigmasterol), or mixtures thereof).

EXAMPLE 2 An emulsion is prepared by conventional methods from the following components: The water phase is formed in a suitable container filled with water as follows: the glycerin is added and then the niacinamide to the water with stirring. The methylparaben dissolved in the benzyl alcohol is added to this mixture with stirring. EDTA is added to this mixture with stirring. The silicone phase is formed in a separate suitable container by adding and stirring together the silicone fluids and the unsubstituted flavanone. The water phase is then added to the silicone phase slowly with stirring to form the emulsion. The resulting composition is applied to wrinkled, aged or sun damaged facial skin of a subject to the amount of 2 mg of composition / cm2 of skin once or twice a day for a period of at least 3-6 months to reduce fine lines and wrinkles and improve the texture of the skin surface. Alternatively, unsubstituted flavanone can be replaced with an equivalent amount of another polycyclic compound (e.g., chalcone, another flavanone, isoflavone, coumarin, flavone, chromone, dicumarol, chromanone, chromanol, triterpenoid (e.g., betulinic acid), sterol (for example, stigmasterol), or mixtures thereof).

EXAMPLE 3 A skin cream is prepared by conventional methods from the following components.

* A C1-C30 monoester or polyester of sugars and one or more carboxylic acid moieties as described herein, preferably a sucrose polyester in which the degree of esterification is 7-8., and in which the fatty acid portions are mono- and / or di-unsaturated C18 and behenic acids, in a molar ratio unsaturated: behenic acid from 1: 7 to 3: 5, most preferably an octaester of sucrose in which there are approximately 7 portions of behenic fatty acid and about 1 portion of oleic acid in the molecule, for example, sucrose ester of cottonseed oil fatty acids. The components of phase A are mixed with a suitable mixer (for example, Tekmar model RW20DZM), heating with stirring at a temperature of about 70-80 ° C. Cetylhydroxyethylcellulose and methylparaben are added with mixing at about 70-80 ° C to melt the components. The components of phase C are mixed separately and milled to obtain a suitably mild mixture (for example, using a Tekmar T50 mill). The mixture of phase C is added to the above mixture and mixed. The bath combination is removed, with continuous agitation, once the temperature reaches approximately 45 ° C. The dimethicone is added and mixed. The components of phase E are mixed separately by mixing until they are uniform and continuous, and then this is added to the previous mixture. The benzyl alcohol is added and mixed, then the NaOH. The pH is adjusted as necessary to 7. The composition is applied to wrinkled, aged or sun damaged skin of a subject in the amount of 2 mg of composition / cm2 of skin once or twice a day for a period of time. at least 3-6 months to reduce fine lines and wrinkles and improve the texture of the skin surface. Alternatively, boswellic acid can be replaced with an equivalent amount of another polycyclic compound (e.g., chalcone, flavanone, soflavone, coumarin, flavone, chromone, dicumarol, chromanone, chromanol, another triterpenoid (e.g., betulinic acid), sterol (for example, stigmasterol), or mixtures thereof).EXAMPLE 4 A skin cream is prepared by conventional methods from the following components.

* See example 3 The components of phase A are mixed with a suitable mixer (for example, Tekmar model RW20DZM). The components of phase B are mixed in phase A with a suitable mixer. The components of phase C are mixed separately until they are uniform. The mixture of phase C is added to the mixture of phases A B, mixed until uniform and emulsified, and then milled to obtain a suitably uniform mixture (for example, using a Tekmar T50 mill). The composition is applied to wrinkled, intrinsically aged or sun damaged skin of a subject in the amount of 2 mg of composition / cm2 of skin once or twice a day for a period of at least about 3-6 months for Improve the surface texture of the skin, including diminishing fine lines and wrinkles. An alternative skin cream having reduced levels of retinol can be prepared in the same manner from the above components, in which the retinol is added in an amount of 0.025% (0.25% retinol at 10% in soybean oil). ), quo sine 100% with water, the amounts of the other components being as shown. Alternatively, the stigmastanol can be replaced with an equivalent amount of another polycyclic compound (e.g., chalcone, flavanone, isoflavone, coumarin, flavone, chromone, dicumarol, chromanone, chromanol, triterpenoid (e.g., betulinic acid), other sterol ( for example, stigmasterol), or mixtures thereof).

Although particular embodiments of the present invention have been described, it will be obvious to those skilled in the art that various changes and modifications may be made to the present invention without departing from the spirit and scope thereof. It is intended to cover, in the appended claims, all such modifications that are within the scope of the present invention.

Claims (8)

NOVELTY OF THE INVENTION CLAIMS

1. - A topical composition comprising: a) a safe and effective amount of a vitamin B3 compound; b) a safe and effective amount of a polycyclic compound selected from the group consisting of: i) flavanones selected from the group consisting of unsubstituted flavanones, monosubstituted flavonones and mixtures thereof; ii) chalcones selected from the group consisting of unsubstituted chalcones, monosubstituted chalcones, disubstituted chalcones, trisubstituted chalcones and mixtures thereof; iii) flavones selected from the group consisting of unsubstituted flavones, monosubstituted flavones, disubstituted flavones and mixtures thereof; iv) one or more isoflavones; v) coumarins selected from the group consisting of unsubstituted coumarins, monosubstituted coumarins, disubstituted coumarins and mixtures thereof; vi) chromones selected from the group consisting of unsubstituted chromones, monosubstituted chromones, disubstituted chromones and mixtures thereof; vii) one or more dicumaroles; viii) one or more chromanones; ix) one or more chromanols; x) esteral selected from the group consisting of stigmasterol, stigmastanol, brasicasterol, campesterol and mixtures thereof; xi) triterpenoids selected from the group consisting of betulinic acid, boswellic acid and mixtures thereof; and xii) mixtures thereof; c) and a dermatologically acceptable vehicle for the vitamin B3 compound and the polycyclic compound.

2. A composition according to claim 1, further characterized in that said vitamin B3 compound is selected from niacinamide, niacinamide derivatives, non-vasodilating esters of nicotinic acid and mixtures thereof.

3. A composition according to any of the preceding claims, further characterized in that said vitamin B3 compound is selected from niacinamide, tocopherol nicotinate and mixtures thereof.

4. A composition according to any of the preceding claims, further characterized in that said vitamin B3 compound is niacinamide.

5. A composition according to any of the preceding claims, further characterized in that said polycyclic compound is selected from the group consisting of flavanones, chalcones or mixtures thereof.

6. A composition according to any of the preceding claims, further characterized in that said polycyclic compound is selected from the group consisting of unsubstituted flavanone, unsubstituted chalcone or a mixture thereof.

7. A composition according to any of the preceding claims, further characterized in that the composition further comprises an additional skin active selected from the group consisting of hydroxy acids, descaling agents, sunscreens, antioxidants, retinoids, wetting agents and mixtures thereof. same.

8. A composition according to any of the preceding claims, further characterized in that the hydroxy acid is salicylic acid; the descaling agent is selected from the group consisting of zwitterionic surfactants and mixtures thereof; the sunblock is selected from the group consisting of zinc oxide, titanium dioxide and mixtures thereof; the sunscreen is selected from the group consisting of 2-ethylhexyl-p-methoxycinnamate, 4,4'-t-butylmethoxydibenzoyl-methane, phenylbenzimidazole sulfonic acid, octocrylene and mixtures thereof; the antioxidant is selected from the group consisting of tocopherol, esters thereof and mixtures thereof; the wetting agent is selected from the group consisting of glycerol, urea, guanidine, petrolatum, panthenol, fatty acid esters of polyols and sugars, and mixtures thereof; and the retinoid is selected from the group consisting of retinol, retinyl acetate, retinyl propionate, and mixtures thereof.