WO1999047116A1

WO1999047116A1 - Skin care compositions

Info

Publication number: WO1999047116A1
Application number: PCT/US1999/005412
Authority: WO
Inventors: Donald Lynn Bissett
Original assignee: The Procter & Gamble Company
Priority date: 1998-03-16
Filing date: 1999-03-12
Publication date: 1999-09-23
Also published as: AU2904499A; JP2002506804A; EP1061898A1; CN1293563A

Abstract

The present invention relates to skin care compositions comprising a vitamin B3 compound at a concentration of above 10 %.

Description

SKIN CARE COMPOSITIONS

FIELD OF THE INVENTION The present invention relates to skin care compositions comprising a vitamin

B3 compound at a concentration of above 10%.

BACKGROUND OF THE INVENTION Niacin, also known as vitamin B3, is the common name for nicotinic acid. The physiologically active form of niacin is niacinamide. Niacin and niacinamide (nicotinamide or nicotinic acid amide) function in the body as a component of two coenzymes: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Until recently, these vitamin B3 compounds were used exclusively to treat niacin deficiency and pellegra.

Today, however, vitamin B3 compounds have also found use in the area of skin care actives. British Patent 1,370,236 describes compositions for skin lightening containing 0.5% to 10% niacin. Similarly, U.S. Patent 4,096,240 discloses the use of

0.1% to 10% niacinamide for skin lightening. It is postulated that these vitamin B3 compounds act by retarding melanin dispersion or distribution into the epidermis.

Notwithstanding such disclosures, the present inventor has found that additional skin care benefits can be acheived by incorporating vitamin B3 compounds at concentrations above 10%, preferably above about 20%.

Specifically, the present inventor has found that at concentrations above 10%, vitamin B3 compounds aid in fading or erasing stretch-marks. Stretch-marks (also termed striae cutis distensae or other similar striae of the skin) are basically defined as the slightly depressed lines on the skin that follow prolonged stretching of the skin. Stretch-marks typically arise from stretching caused by pregnancy, obesity, etc. Stretch-marks commonly appear on the abdomen, breasts, and thighs, although other body sites may be involved.

It is, therefore, an object of the present invention to provide skin care compositions containing above 10% of a vitamin B3 compound. 2

It is also an object of the present invention to treat and/or prevent stretch- marks and the like by applying to the skin compositions containing a vitamin B3 compound at concentrations above 10%.

These and other objects will become readily apparent from the detailed description which follows.

SUMMARY OF THE INVENTION The present invention relates to methods of treating stretch-marks by administering a safe and effective amount of a skin care composition comprising: a), at least above about 10% of a stretch-mark fading agent selected from the group consisting of vitamin B3 compounds and mixtures thereof; and b). a dermatologically acceptable carrier for said vitamin B3 compound. The present invention further relates to articles of manufacture comprising a skin care composition comprising from about 0.1% to about 40% of a vitamin B3 compound in a package for said skin care composition in association with the information about and/or instructions on the use of vitamin B3 compounds to treat stretch-marks.

Unless otherwise indicated, all percentages and ratios used herein are by weight of the total composition. All weight percentages, unless otherwise indicated, are on an actives weight basis. All measurements made are at approximately 25°C, unless otherwise designated. The term "safe and effective amount" as used herein means an amount of a compound or composition sufficient to significantly induce a positive benefit, preferably a positive skin appearance or feel benefit, including independently the benefits disclosed herein, but low enough to avoid serious side effects, i.e., to provide a reasonable benefit to risk ratio, within the scope of sound judgment of the skilled artisan.

DETAILED DESCRIPTION OF THE INVENTION

The skin moisturizing compositions used in the present invention can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well any of the additional or optional ingredients, components, or limitations described herein.

ESSENTIAL COMPONENTS 3

Vitamin B3 component

The compositions used in the present invention comprise a safe and effective amount of a natural or synthetic vitamin B3 compound. The compositions used in the present invention preferably comprise from above 10% to about 50%, more preferably from about 12% to about 50%, even more preferably from about 20% to about 40% of the vitamin B3 compound.

As used herein, "vitamin B3 compound" means a compound having the formula:

O Nr^' wherein R is - CONH2 (i.e., niacinamide), - COOH (i.e., nicotinic acid) or - CH2OH (i.e., nicotinyl alcohol); derivatives thereof; and salts of any of the foregoing.

Exemplary derivatives of the foregoing vitamin B3 compounds include nicotinic acid esters, including non-vasodilating esters of nicotinic acid, nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide.

Suitable esters of nicotinic acid include nicotinic acid esters of C1-C22, preferably C1-C16, more preferably C1-C6 alcohols. The alcohols are suitably straight-chain or branched chain, cyclic or acyclic, saturated or unsaturated (including aromatic), and substituted or unsubstituted. The esters are preferably non- rubifacient. As used herein, "non-rubifacient" means that the ester does not commonly yield a visible flushing response after application to the skin in the subject compositions (the majority of the general population would not experience a visible flushing response, although such compounds may cause vasodilation not visible to the naked eye). Alternatively, a nicotinic acid material which is rubifacient at higher doses could be used at a lower dose to reduce the rubifacient effect. Non-rubifacient esters of nicotinic acid include tocopherol nicotinate and inositol hexanicotinate; tocopherol nicotinate is preferred.

Other derivatives of the vitamin B3 compound are derivatives of niacinamide resulting from substitution of one or more of the amide group hydrogens. Nonlimiting examples of derivatives of niacinamide useful herein include nicotinyl amino acids, derived, for example, from the reaction of an activated nicotinic acid compound (e.g., nicotinic acid azide or nicotinyl chloride) with an amino acid, and nicotinyl alcohol esters of organic carboxylic acids (e.g., Cl - C18). Specific examples of such derivatives include nicotinuric acid and nicotinyl hydroxamic acid, which have the following chemical structures: nicotinuric acid: o o

II II NH— CH₂— COH

nicotinyl hydroxamic acid:

Exemplary nicotinyl alcohol esters include nicotinyl alcohol esters of the carboxylic acids salicylic acid, acetic acid, glycolic acid, palmitic acid and the like. Other non-limiting examples of vitamin B3 compounds useful herein are 2- chloronicotinamide, 6-aminonicotinamide, 6-methylnicotinamide, n-methyl- nicotinamide, n,n-diethylnicotinamide, n-(hydroxymethyl)-nicotinamide, quinolinic acid imide, nicotinanilide, n-benzylnicotinamide, n-ethylnicotinamide, nifenazone, nicotinaldehyde, isonicotinic acid, methyl isonicotinic acid, thionicotinamide, nialamide, l-(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 a number of sources, e.g., the Sigma Chemical Company (St. Louis, MO); ICN Biomedicals, Inc. (Irvin, CA) and Aldrich Chemical Company (Milwaukee, WI).

One or more vitamin B3 compounds may be used herein. Preferred vitamin B3 compounds are niacinamide and tocopherol nicotinate. Niacinamide is more preferred. 5

When used, salts, derivatives, and salt derivatives of niacinamide are preferably those having substantially the same efficacy as niacinamide in the methods of regulating skin condition described herein.

Salts of the vitamin B3 compound are also useful herein. Nonlimiting examples of salts of the vitamin B3 compound useful herein include organic or inorganic salts, such as inorganic salts with anionic inorganic species (e.g., chloride, bromide, iodide, carbonate, preferably chloride), and organic carboxylic acid salts (including mono-, di- and tri- Cl - C18 carboxylic acid salts, e.g., acetate, salicylate, glycolate, lactate, malate, citrate, preferably monocarboxylic acid salts such as acetate). These and other salts of the vitamin B3 compound can be readily prepared by the skilled artisan, for example, as described by W. Wenner, "The Reaction of L- Ascorbic and D-Isoascorbic 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 the vitamin B3 compound is substantially chemically free (e.g., unbound and/or unhindered), or after delivery to the skin becomes substantially chemically free ("chemically free" is hereinafter alternatively referred to as "uncomplexed"). More preferably, the vitamin B3 compound is essentially uncomplexed. Therefore, if the composition contains the vitamin B3 compound in a salt or otherwise complexed form, such complex is preferably substantially reversible, more preferably essentially reversible, upon delivery of the composition to the skin. For example, such complex should be substantially reversible at a pH of from about 5.0 to about 6.0. Such reversibility can be readily determined by one having ordinary skill in the art. More preferably the vitamin B3 compound is substantially uncomplexed in the composition prior to delivery to the skin. Exemplary approaches to minimizing or preventing the formation of undesirable complexes include omission of materials which form substantially irreversible or other complexes with the vitamin B3 compound, pH adjustment, ionic strength adjustment, the use of surfactants, and formulating wherein the vitamin B3 compound and materials which complex 6

therewith are in different phases. Such approaches are well within the level of ordinary skill in the art.

Thus, in a preferred embodiment, the vitamin B3 compound contains a limited amount of the salt form and is more preferably substantially free of salts of a vitamin B3 compound. Preferably the vitamin B3 compound contains less than about 50% of such salt, and is more preferably essentially free of the salt form. The vitamin B3 compound in the compositions hereof having a pH of from about 4 to about 7 typically contain less than about 50% of the salt form.

The vitamin B3 compound may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural

(e.g., plant) sources. The vitamin B3 compound is preferably substantially pure, more preferably essentially pure.

Without being limited by theory, at concentrations above 10%, by weight of the composition, vitamin B3 compounds stimulate skin metabolism and turnover or replacement of the affected structural proteins (e.g., collagen), hence, fading or erasing the stretch marks and returning the skin to its normal appearance.. By the phrase "stretch-mark fading agent," as used herein, is meant an agent useful in fading and/or erasing the visible appearance on skin of stretch marks.

Carrier The compositions used in the present invention also contain a dermatologically acceptable carrier. The phrase "dermatologically-acceptable carrier", as used herein, means that the carrier is suitable for topical application to the skin, has good aesthetic properties, is compatible with the actives of the present invention and any other components, and will not cause any untoward safety or toxicity concerns. A safe and effective amount of carrier is from about 50% to about

99.99%, preferably from about 99.9% to about 80%, more preferably from about

98% to about 90%, most preferably from about 95% to 90% of the composition.

The carrier can be in a wide variety of 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 useful herein. These emulsions can cover a broad range of viscosities, e.g, from about 100 cps to about 200,000 cps. These emulsions 7

can also be delivered in the form of sprays using either mechanical pump containers or pressurized aerosol containers using conventional propellants. These carriers can also be delivered in the form of a mousse. Other suitable topical carriers include anhydrous liquid solvents such as oils, alcohols, and silicones (e.g., mineral oil, ethanol, isopropanol, dimethicone, cyclomethicone, and the like); aqueous-based single phase liquid solvents (e.g., hydro-alcoholic solvent systems); and thickened versions of these anhydrous and aqueous-based single phase solvents (e.g., where the viscosity of the solvent has been increased to form a solid or semi-solid by the addition of appropriate gums, resins, waxes, polymers, salts, and the like). Examples of topical carrier systems useful in the present invention are described in the following four references all of which are incorporated herein 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); U.S. Patent No. 4,960,764 to Figueroa et al., issued October 2, 1990; and U.S. Patent No. 4,254,105 to Fukuda et al., issued March 3, 1981.

The carriers of the skin care compositions can comprise from about 50% to about 99%> by weight of the compositions used in the present invention, preferably from about 75% to about 99%, and most preferably from about 85% to about 95%. Preferred cosmetically and/or pharmaceutically acceptable topical carriers include hydro-alcoholic systems and oil-in-water emulsions. When the carrier is a hydro-alcoholic system, the carrier can comprise from about 0% to about 99% of ethanol, isopropanol, or mixtures thereof, and from about 1% to about 99% of water. More preferred is a carrier comprising from about 5% to about 60% of ethanol, isopropanol, or mixtures thereof, and from about 40% to about 95% of water. Especially preferred is a carrier comprising from about 20% to about 50% of ethanol, isopropanol, or mixtures thereof, and from about 50% to about 80% of water. When the carrier is an oil-in-water emulsion, the carrier can include any of the common excipient ingredients for preparing these emulsions. A more detailed discussion of suitable carriers is fount in U.S. Patent 5,605,894 to Blank et al., and in PCT application WO 97/39733, published October 30, 1997, to Oblong et al., both herein incorporated by reference in their entirety. 8

OPTIONAL COMPONENTS The compositions used in the present invention may optionally comprise additional skin actives. Non-limiting examples of such skin actives include hydroxy acids such as salicylic acid; desquamatory agents such as zwitterionic surfactants; sunscreens such as 2-ethylhexyl-p-methoxycinnamate, 4,4'-t-butyl methoxydibenzoyl- methane, octocrylene, phenyl benzimidazole sulfonic acid; sun-blocks such as zinc oxide and titanium dioxide; anti-inflammatory agents; corticosteroids such as hydrocortisone, methylprednisolone, dexamethasone, triamcinolone acetconide, and desoxametasone; anesthetics such as benzocaine, dyclonine, lidocaine and tetracaine; antipruitics such as camphor, menthol, oatmeal (colloidal), pramoxine, benzyl alcohol, phenol and resorcinol; anti-oxidants/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 protectants. Mixtures of any of the above mentioned skin actives may also be used. A more detailed description of these actives is found in U.S. Patent 5,605,894 to Blank et al. (previously incorporated by reference). Preferred skin actives include hydroxy acids such as salicylic acid, sunscreen, antioxidants and mixtures thereof. Other conventional skin care product additives may also be included in the compositions used in 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, pyrrolidone carboxylic acid/salt (PCA), trimethyl glycine (betaine), tranexamic acid, amino acids (e.g., serine, alanine), panthenol and its derivatives, collagen, hyaluronic acid, elastin, hydrolysates, primrose oil, jojoba oil, epidermal growth factor, soybean saponins, mucopolysaccharides, and mixtures thereof may be used. Other suitable additives or skin actives are discussed in further detail in PCT application WO 97/39733, published October 30, 1997, to Oblong et al., herein incorporated by reference in its entirety. 9

Preparation of Skin Care Compositions The compositions used in the present invention are generally prepared by conventional methods such as are known in the art of making topical compositions. Such methods typically involve mixing of the ingredients in one or more steps to a relatively uniform state, with or without heating, cooling, application of vacuum, and the like. Non-limiting examples of the product form can be a gel, emulsion, lotion, cream, ointment, solution, liquid, etc.

Methods for Treating Stretch-marks The methods of the present invention are useful for treating or preventing stretch-marks, especially in the dermis and epidermis of mammalian skin. The methods of the present invention involve topically applying to the skin an effective amount of the skin care composition of the present invention. The amount of the composition which is applied, the frequency of application and the period of use will vary widely depending upon the level of vitamin B3 compound and/or other components of a given composition and the degree of fading desired.

The skin care compositions used in the present invention can be chronically applied to the skin. By "chronic topical application" is meant continued topical application of the composition over an extended period during the subject's lifetime, preferably for a period of at least about one week, more preferably for a period of at least about two weeks, even more preferably for a period of at least one month, even more preferably for at least about three months, even more preferably for at least about six months, and more preferably still for at least about one year. While benefits are obtainable after various maximum periods of use (e.g., five, ten or twenty years), it is preferred that chronic application continue throughout the subject's lifetime to maintain and/or increase the benefits achieved. Typically applications would be on the order of one to four times per day over such extended periods, however application rates can be more than four times per day, especially on areas particularly prone to stretch-mark problems, such as the abdomin and upper chest area. A wide range of quantities of the compositions used in the present invention can be employed to provide a skin appearance and/or feel benefit. Quantities of the 10

present compositions which are typically applied per application are, in mg composition cm2 skin, from about 0.1 mg/cm2 to about 10 mg/cm2. A particularly useful application amount is about 2 mg/cm2.

The method of treating stretch-marks is preferably practiced by applying a composition in the form of a skin lotion, cream, gel, cosmetic, emulsion, or the like which is intended to be left on the skin for some aesthetic, prophylactic, therapeutic or other benefit (i.e., a "leave-on" composition). After applying the composition to the skin, it is preferably left on the skin for a period of at least about 15 minutes, more preferably at least about 30 minutes, even more preferably at least about 1 hour, most preferably for at least several hours, e.g., up to about 12 hours.

Another approach to ensure a continuous exposure of the skin to at least a minimum level of vitamin B3 compound is to apply the compound by use of a patch. Such an approach is particularly useful for problem skin areas needing more intensive treatment. The patch can be occlusive, semi-occlusive or non-occlusive. The vitamin B3 compound composition can be contained within the patch or be applied to the skin prior to application of the patch. The patch can also include additional actives such as chemical initiators for exothermic reactions such as those described in PCT application WO 9701313 to Burkett et al. Preferably the patch is applied at night as a form of night therapy.

EXAMPLES

The following examples further describe and demonstrate embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope of the invention.

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 then applying to to the skin from about from about 0.5 g to about 50g. 11

Ingredient % Weight

Glycerine 6.933

Niacinamide 15.000

Permethyl 101 A 1 3.000

Sepigel 2 2.500

Q2-1403 3 2.000

Isopropyl Isostearate 1.330

Arlatone 2121 4 1.000

Cetyl Alcohol CO- 1695 0.720

SEFA Cottonate 5 0.670

Tocopherol Acetate 0.500

Panthenol 0.500

Adol 62 6 0.480

Kobo Titanium Dioxide 0.400

Sodium Hydroxide 50% 0.0125

Aqueous

Fiery 5 7 0.150

Disodium EDTA 0.100

Glydant Plus 8 0.100

Myrj 59 9 0.100

Emersol 132 10 0.100

Color 0.00165

Purified Water q.s. to 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 then applying to to the skin from about from about 0.5 g to about 50g. 12

Ingredient % Weight

Glycerine 6.933

Tocopherol nicotinate 12.000

Permethyl 101 A 1 3.000

Sepigel 2 2.500

Q2-1403 3 2.000

Isopropyl Isostearate 1.330

Arlatone 2121 4 1.000

Cetyl Alcohol CO- 1695 0.720

SEFA Cottonate 5 0.670

Tocopherol Acetate 0.500

Panthenol 0.500

Adol 62 6 0.480

Kobo Titanium Dioxide 0.400

Sodium Hydroxide 50% 0.0125

Aqueous

Fiery 5 7 0.150

Disodium EDTA 0.100

Glydant Plus 8 0.100

Myrj 59 9 0.100

Emersol 132 10 0.100

Color 0.00165

Purified Water q.s. to 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 then applying to to the skin from about from about 0.5 g to about 50g.

Ingredient % Weight

Glycerine 6.933 13

Niacinamide 12.000

Permethyl 101 A 1 4.000

Q2-1403 3 2.000

Isopropyl Isostearate 1.330

Arlatone 2121 4 1.000

Cetyl Alcohol CO-1695 0.720

SEFA Cottonate 5 0.670

Carbopol 95411 0.500

Tocopherol Acetate 0.500

Panthenol 0.500

Adol 62 6 0.480

Kobo Titanium Dioxide 0.400

Sodium Hydroxide 50% 0.250

Aqueous

Fiery 5 7 0.150

Disodium EDTA 0.100

Glydant Plus 8 0.100

Myrj 59 9 0.100

Emersol 132 10 0.100

Carbopol 138212 0.100

Color 0.00165

Purified Water q.s. to 100

1. Isohexadecane, Presperse Inc., South Plainfield, NJ

2. Polyacrylamide(and)C13-14 Isoparaffin(and)Laureth-7, Seppic Corporation, Fairfield, NJ

3. dimethicone(and)dimethiconol, Dow Corning Corp., Midland, MI

4. Sorbitan Monostearate and Sucrococoate, ICI Americas Inc., Wilmington, DE 14

5. Sucrose ester of fatty acid, Procter and Gamble, Cincinnati, OH

6. Stearyl Alcohol, Procter and Gamble, Cincinnati, OH

7. Fiery 5 n/a, Procter and Gamble, Cincinnati, OH

5 8. DMDM Hydantoin (and) lodopropynyl Butylcarbamate,

Lonza Inc., Fairlawn, NJ

9. PEG- 100 Stearate, ICI Americas Inc. , Wilmington, DE

10. Stearic acid, Henkel Corp., Kankakee, EL

11. Carbomer, BF Goodrich, Cleveland OH lo 12. Carbomer, BF Goodrich, Cleveland OH

Claims

15WHAT IS CLAIMED IS:

1. A method of treating and/or preventing stretch-marks by administering a safe and effective amount of a skin care composition comprising: a), at least above 10% of a stretch-mark fading agent selected from the group consisting of vitamin B3 compounds and mixtures thereof; and b). a dermatologically acceptable carrier for said vitamin B3 compound.

2. A method according to Claim 1, wherein the concentration of the stretch- mark fading agent is from 10% to 25%.

3. A method according to any one of the preceding Claims, wherein said vitamin

B3 compound is selected from niacinamide, derivatives of niacinamide, non- vasodilating esters of nicotinic acid, and mixtures thereof.

4. A method according to any one of the preceding Claims, wherein said vitamin

B3 compound is selected from niacinamide, tocopherol nicotinate, and mixtures thereof.

5. A method according to any one of the preceding Claims, wherein said vitamin

B3 compound is niacinamide.

6. A method according to any one of the preceding Claims, wherein said vitamin

B3 compound is substantially free of salts of the vitamin B3 compound.

7. A method according to any one of the preceding Claims, wherein the composition further comprises an additional skin active selected from the group consisting of hydroxy acids, desquamatory agents, sunscreens, anti- oxidants, retinoids and mixtures thereof.

8. A method according to any one of the preceding Claims, wherein the hydroxy acid is salicylic acid; the desquamatory agent is selected from the group consisting of zwitterionic surfactants and mixtures thereof; the sun-block 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, 16

phenyl benzimidazole sulfonic acid, octocrylene and mixtures thereof; the anti-oxidant is selected from the group consisting of tocopherol, esters thereof and mixtures thereof; and the retinoid is selected from the group consisting of retinol, retinyl acetate, retinyl propionate, and mixtures thereof.

9. A method according to any one of the preceding Claims, wherein the skin care composition is contained within a patch or is applied to the skin and covered by a patch.

10. An article of manufacture comprising a skin care composition comprising from 0.1% to 40% of a vitamin B3 compound in a package for said skin care composition in association with the information about and/or instructions on the use of vitamin B3 compounds to treat stretch-marks