MXPA00009058A - Method of reducing cellulite in mammalian skin - Google Patents

Abstract

The present invention relates to a method for combating cellulite or reducing localized fatty excesses which comprises administering to a person having cellulite or localized fatty excesses a body slimming amount of a composition containing niacinamide.

Description

METHOD TO REDUCE CELLULITE IN MAMMALIAN SKIN FIELD OF THE INVENTION The present invention relates to a method for combating cellulite or reducing localized fat excesses comprising the administration of a quantity for body thinning of a composition containing niacinamide to a person having cellulite or localized excess fat.

BACKGROUND OF THE INVENTION Suffering from cellulitis is a difficult problem that causes emotional and psychological upheaval in many women. Cellulitis mainly affects the thighs and buttocks but can also occur in the stomach and upper arms. Frequently, cellulite presents an appearance of crumbly orange peel, not perceptible. Clinically, ceiulitis manifests a variety of symptoms including thinning of the epidermis, reduction and decomposition of the microvasculature that leads to subdermal fluid accumulations, and subdermal agglomerations of fatty tissue. It has been observed that polymeric proteoglycans are a major component of these agglomerations.

To release these agglomerations and trapped fatty fluids, the local application of enzymes or compositions containing enzymes has been proposed because the enzymes are capable of depolymerizing the proteoglycans. These enzymes include mucopolysaccharidases and, in particular, hyaluronidase, thiomucase and a-mucase. Among the methods to stimulate lipolysis, the most commonly known and used is that which inhibits phosphodiesterase in order to avoid or at least limit the degree of degradation of cyclic AMP. In effect, phosphodiesterase destroys cyclic AMP by transforming it into 5 'AMP so that it can not function as a lipolysis activator. It is then important to inhibit the activity of the phosphodiesterase so that a high amount of cyclic AMP is present at the level of the adipocytes thus stimulating the lipolytic activity. Various representative phosphodiesterase inhibitors, which are known as thinning agents, include in particular xanthine derivatives and particularly theophylline, caffeine and theobromine. Furthermore, it is known to use certain oil-soluble plant extracts which, according to a different mechanism, can act as a thinning agent. For example, in the patent of E.U.A. No. 4,795,638 discloses a thermo-thinning cosmetic composition containing an oil-soluble plant extract having a thinning action. Representative examples of these oil-soluble plant extracts are vegetable extracts that include mainly, those of climber (Hederá Helix), arnica (Arnica Montana), rosemary (Rosmarinus Officinalis N), calendula (Calendula officinalis), sage (Salvia officinalis) N), ginseng (Panax Ginseng), (Hypericum Perforatum), ruscus (Ruscus aculeatus), ulmaria (Fílapendula ulmaria L) and ortosifon (Ortosifon Stamincus Benth), as well as mixtures of these plant extracts. Regardless of such descriptions, there is a need to obtain improved compositions for reducing cellulite in mammalian skin. The present inventor has found that skin care compositions containing niacynamide help reduce cellulite in the skin. Also, it is an object of the present invention to provide methods for reducing cellulite in mammalian skin. Another object of the present invention is to provide skin compositions, which are applied topically to reduce cellulite, and which contain a safe and effective amount of niacinamide. These and other objects will be apparent from the following detailed description.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to methods of treatment and / or prevention of cellulite by administering a safe and effective amount of a composition for skin care comprising: (a) a safe and effective amount of niacynamide; and (b) a dermatologically acceptable vehicle for niacinamide. The present invention also relates to articles of manufacture comprising a composition for skin care comprising from about 0.1% to about 40%, by weight, of niacinamide in a package for said composition for skin care in together with information and / or instructions on the use of niacinamide to treat cellulite. Unless otherwise indicated, all percentages and ratios used herein are by weight of the total composition. All percentages by weight, unless otherwise indicated, are on a weight basis of the active compounds. All measurements made are at approximately 25 ° C, unless otherwise indicated. 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 skin appearance or sensation benefit, including independently the benefits described herein. , but low enough to avoid serious side effects, that is, provide a reasonable ratio of benefit to risk, within the scope of the solid judgment of the person skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION The compositions used in the present invention may comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as of any of the additional or optional ingredients, components or limitations described in the present invention.

ESSENTIAL COMPONENTS Niacinamide Nicotinic acid and niacinamide (nicotinamide or nicotinic acid amide) are water-soluble vitamins, whose physiologically active forms of nimotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) play a major role as coenzymes in a variety of important metabolic reactions. Nicotinic acid is an essential dietary constituent, which itself is lacking leading to pellagra, a condition characterized by an erythematous skin rash as well as gastrointestinal and neurological symptoms. Nicotinic acid and niacinamide have been used routinely to treat pellagra because they are therapeutic. Nicotinic acid as well as niacynamide are available from a variety of pharmaceutical houses such as Armor Pharmaceutical Company located in Phoenix, Ariz .; Brown Pharmaceutical Company Inc. located in Los Angeles, Calif .; and Keith Pharmaceutical Inc. located in Miami, Fia. Without trying to be limited by theory, it is believed that niacinamide reduces cellulite by several mechanisms. Niacinamide stimulates epidermal cells and will therefore thicken the tissue to counteract the thinning of the epidermis that is associated with cellulite. These compounds are also vasoactive (stimulate blood flow) and therefore improve the reduction in microvascularization associated with cellulitis. Additionally, niacinamide stimulates metabolism in skin cells in general (e.g., epidermis, dermis, subcutaneous fat) that increases the cellular production of enzymes for removal of fatty tissue agglomerations and / or proteoglycans. The niacynamide is preferably present in the compositions used in the present invention in concentrations of from about 0.1% to about 50%, most preferably from about 1% to about 30%, and still most preferably from about 1% to about 20% , most preferably from about 1% to about 10%.

Vehicle The compositions used in the present invention also comprise a dermatologically acceptable vehicle. The phrase "dermatologically acceptable vehicle", as used herein, means that the vehicle is suitable for topical application on the skin, has suitable aesthetic properties, is compatible with the active ingredients of the present invention and with any other component, and It 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, dimeticon, cyclomethicone, and the like); liquid solvents of individual phase of aqueous base (for example, systems of hydra-alcoholic solvents); and thickened versions of these anhydrous and water-based individual phase solvents (eg, wherein 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 & Toíletries, 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 hydra-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. A vehicle comprising about 20% to about 50% ethanol, isopropanol or mixtures thereof, and about 50% to about 80% water is especially preferred. 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 PCT application WO 97/39733, published October 30, 1997, to Oblong et al., Both are incorporated herein by reference in their entirety.

Optional Components The compositions used in the present invention may optionally comprise additional materials including slimming agents as well as additional active ingredients useful in providing cellulite control. Among these agents are phosphodiesterase inhibitors (eg, xanthine derivatives such as theophylline, caffeine, theobromine or salts thereof such as aminophylline) and certain oil-soluble plant extracts, including, in particular, those of climber (Hederá Helix), arnica (Arnica Montana), rosemary (Rosmarinus Officinalis N), calendula (Calendula officinalis), sage (Salvia officinaalis N), ginseng (Panax Ginseng), (Hypericum Perforatum), ruscus (Ruscus aculeatus), ulmaria (Fílapendula ulmaria L) and ortosífon (Ortosifon Stamíncus Benth), as well as mixtures of these extracts of vegetables, all the previous ones described in the patent of EUA 4,795,638, incorporated herein by reference. Herbal and / or botanical extracts such as those described in the U.S. Patents are also useful. 5,705,170 and 5,667,793 both incorporated herein by reference. Mixtures of any of the above additional materials may also be used. The compositions used in 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; desquamation 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; corticosteroids such as hydrocortisone, methylprednisolone, dexamethasone, triamcinolone acetconide, and deoxametasone; anesthetics such as benzocaine, dyclonine, lidocaine and tetracaine; antituritics such as camphor, menthol, oat (colloidal), pramoxine, benzyl alcohol, phenol and resorcinol; antioxidants / radical scavengers such as tocopherol and esters thereof; chelators; retinoids such as retinol, retinyl palmitate, retinyl acetate, retinyl propionate and retinal; hydroxy acids such as glycolic acid; keto acids such as pyruvic acid; N-acetyl-L-cysteine and derivatives thereof; benzofuran derivatives; 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 active ingredients 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 stearate, ethyl isostearate, cetyl ricinoleate, sononyl sononanoate, sohexadecane, lanolin, lanolin esters, cholesterol , carboxylic acid / pyrrolidone salt (PCA), trimethylglycine (betaine), tranexamic acid, amino acids (eg, serine, alanine), panthenol and its derivatives, collagen, hyaluronic acid, elastin, hydrolysates, rose oil, jojoba oil , epidermal growth factor, soy saponins, mucopolysaccharides and mixtures thereof. Other suitable skin additives or active ingredients are described in greater detail in the PCT application WO 97/39733, published October 30, 1997, to Oblong et al., And incorporated herein by reference in its entirety.

Preparation of skin care compositions The compositions that are used in 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. Non-limiting examples of the product form can be gel, emulsion, lotion, cream, ointment, solution, liquid, etc.

Methods for the treatment of cellulite The methods of the present invention are useful for treating or preventing cellulite, especially in the subcutaneous tissues, dermis and epidermis of mammalian skin. The methods of the present invention are to apply topically to the skin an effective amount of the skin care composition herein. 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 niacinamide and / or the other components of a certain composition, and the degree of cellulite fading desired. The skin care compositions used in the present invention are 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 over a period of at least about one week, preferably over a period of about two weeks, most preferably during a period of at least about one month, still most preferably about three months, even most 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 to maintain and / or increase the benefits achieved. Applications will typically be in the order of one to four times a day during such extended periods, however application rates may be more than four times a day, especially on areas prone to agglomerations of fat and water such as thighs and the buttocks. 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 method for treating cellulite is preferably carried out by applying a composition in the form of a lotion, gel, cosmetic or the like for the skin that is intended to be left on the skin for aesthetic, prophylactic, therapeutic, and other benefits (i.e. a "non-rinsing" composition). After applying the composition to the skin, it is preferably left on the skin for a period of at least 15 minutes, most preferably at least about 30 minutes, still more preferably at least about 1 hour, and preferably for at least several hours, for example, up to about 12 hours. Another approach to ensure continuous exposure of the skin to at least a minimum level of niacinamide is to apply the compound by the use of a patch. 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 niacynamide composition may be contained in the patch or applied to the skin prior to 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 applied overnight as a form of nocturnal therapy.

EXAMPLES The following examples describe and demonstrate 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 The following is an example of a skin cream incorporating the compositions of the present invention. The compositions are formed by combining and mixing the ingredients of each column using conventional technology and applying them to the skin of about 0.5 g to about 50 g.

Ingredient% by weight Glycerin 6,933 Niacínamida 15,000 Permetil 101A1 3,000 Sepigel2 2,500 Q2-14033 2,000 Isopropyl isostearate 1,330 Arlatone 21214 1,000 Cetyl alcohol CO-1695 0.720 SEAC cottonate »5 0.670 Tocopherol acetate 0.500 Panthenol 0.500 Adol 626 0.480 Titanium dioxide-kobo 0.400 Sodium hydroxide 50% 0.0125 Aqueous Fiery 57 0.150 Disodium EDTA 0.100 Glydant Plus8 0.100 Myrj 599 0.100 Emersol 13210 0.100 Color 0.00165 Purified water cbp 100 EXAMPLE 2 The following is an example of a skin cream incorporating the compositions of the present invention. The compositions are formed by combining and mixing the ingredients of each column using conventional technology and applying them to the skin of about 0.5 g to about 50 g.

I nq network weight% Glycerin 6,933 Niacinamide 12,000 Permethyl 101 A1 3,000 Sepigel2 2,500 Q2-14033 2,000 Isopropyl isostearate 1,330 Arlateme 21214 1,000 Cetyl alcohol CO-1695 0.720 SEAC cottonate »5 0.670 Tocopherol acetate 0.500 Panthenol 0.500 Adol 626 0.480 Dioxide titanium-kobo 0.400 Sodium hydroxide 50% 0.0125 Aqueous Fiery 57 0.150 Disodium EDTA 0.100 Glydant Plus8 0.100 Myrj 599 0.100 Emersol 13210 0.100 Color 0.00165 Purified water cbp 100 EXAMPLE 3 The following is an example of a skin cream incorporating the compositions of the present invention. The compositions are formed by combining and mixing the ingredients of each column using conventional technology and applying them to the skin of about 0.5 g to about 50 g.

Ingredient% by weight Glycerin 6,933 Niacinamide 12,000 Permethyl 101 A1 4,000 Q2-14033 2,000 Isopropyl isostearate 1,330 Arlateme 21214 1,000 Cetyl alcohol CO-1695 0.720 SEAC cottonate5 0.670 Carbopol 95411 0.500 Tocopherol acetate 0.500 Panthenol 0.500 Adol 626 0.480 Titanium dioxide-kobo 0.400 Sodium hydroxide 50% 0.250 Aqueous Fiery 57 0.150 Disodium EDTA 0.100 Giydant Plus8 0.100 Myrj 599 0.100 Emersol 13210 0.100 Color 0.00165 Purified water cbp 100 1. Isohexadecane, Presperse Inc., South Plainfield, NJ 2. Polyacrylamide (y) C13-14 Isoparaffin (y) Laureth-7, Seppíc Corporation, Fairfield, NJ 3. dimethicone (y) dimethiconol, Dow Corning Corp., Midland, Ml 4 Sorbitan monostearate and Sucrococoate, ICI Americas Inc., Wilmington, DE 5. Fatty acid sucrose ester, Procter and Gamble, Cincinnati, OH 6. Stearyl alcohol, Procter and Gamble, Cincinnati, OH 7. Fiery 5 n / a , Procter and Gamble, Cincinnati, OH 8. DMDM Hydantoin (and) Iodopropynyl Butylcarbamate, Lonza Inc., Fairlawn, NJ 9. PEG-100 Stearate, ICI Americas Inc., Wilmington, DE 10. Stearic Acid, Henkel Corp., Kankakee, IL 11. Carbomer, BF Goodrich, Cleveland OH 12. Carbomer, BF Goodrich, Cleveland OH

Claims (9)

NOVELTY OF THE INVENTION CLAIMS

1. - A skin care composition for treating and / or preventing cellulitis in a mammal that has, or is prone to form cellulite, comprising: a) a safe and effective amount of niacinamide; and b) a dermatologically acceptable vehicle for the niacynamide.

2. The composition according to claim 1, further characterized in that the concentration of niacinamide is from 1% to 20%.

3. The composition according to any of the preceding claims, further characterized in that the niacinamide is substantially non-complex.

4. The composition according to any of the preceding claims, further characterized in that the composition comprises an additional active selected from the group consisting of phosphodiesterase inhibitors, oil-soluble plant extracts, herbal extracts, botanical extracts and mixtures thereof.

5. The composition according to any of the preceding claims, further characterized in that the additional active is a phosphodiesterase inhibitor selected from the group consisting of theophylline, caffeine, theobromine, salts thereof and mixtures thereof.

6. The composition according to any of the preceding claims, further characterized in that it comprises an additional skin active selected from the group consisting of hydroxy acids, desquamation agents, sunscreens, antioxidants, retinoids and mixtures thereof.

7. The composition according to any of the preceding claims, further characterized in that the hydroxy acid is salicylic acid; the desquamation 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-butyl methoxydibenzoyl-methane, phenylbenzimidazole sulfonic acid, octocrylene and mixtures thereof; the antioxidant is selected from the group consisting of tocopherol, esters thereof and mixture thereof; and the retinoid is selected from the group consisting of retinol, retinyl acetate, retinyl propionate and mixtures thereof.

8. The composition according to any of the preceding claims, further characterized in that the composition for skin care is contained within a patch or applied to the skin and covered by a patch.

9. An article of manufacture comprising a composition for skin care comprising from 0.1% to 40%, by weight, of niacinamide in a package for said composition for skin care.