CZ20011527A3 - Oil-in-water emulsion - Google Patents

Abstract

Disclosed is an oil-in-water emulsion comprising: (a) a water-soluble ascorbic acid compound; (b) a metallic oxide; (c) a structuring compound; (d) a hydrophobic component; and (e) a hydrophilic liquid carrier, wherein the emulsion has a pH of from about 6 to about 10.

Description

EMULSION OIL IN WATER

TECHNICAL FIELD

The present invention describes compositions for topical application. In particular, it discloses surface compositions comprising emulsions for skin lightening.

BACKGROUND OF THE INVENTION

Customers usually use cosmetic products for skin care as well as for improving the health and / or physical appearance of the skin. Rough skin areas, or injuries and hyperpigmented areas (such as liver spots, freckles and brown spots associated with skin aging, or external skin damage to human skin) are areas that usually require treatment. People from some parts of Asia are also interested in skin lightening.

Irradiation with ultraviolet (UV) light results in sunburn which causes skin darkening and / or hyperpigmentation. It is generally known that conditions leading to the damage or loss of tyrosinase, the enzyme responsible for the production of melanin, lead to hyperpigmentation, that is, to albinism. Irradiation with UV rays, as a result of exposure to sunlight, leads to the formation of a melanin complex in melanocytes located in the basal zone of the epidermis. Melanin is then released from melanocyte dendrites, penetrating the keratinocytes, resulting in hyperpigmentation of the skin. This hyperpigmentation may then take the form of dots, freckles, spots, undesirable total darkening and / or unevenness of the basal skin,

A wide range of substances and / or additives, such as: ascorbic acid and its derivatives, kojic acid and its derivatives, hydroquinone, arbutin, and a wide variety of extracts such as Glycyrrhiza plant extract known in the art and commonly available for use in skin lightening compositions. In recent years, modern synthetic substances have also been available for skin lightening in a wide range of available forms.

L-ascorbic acid (i.e., vitamin C) is a useful component of skin lightening and / or leveling agents as well as a reductant, UV absorbent and melanin inhibitor in cosmetics. GB2259014-A, Hadas et al., 1998 discloses a skin lightening composition comprising oil soluble ascorbic acid derivatives such as ascorbic acid palmitate together with sunscreening agents such as titanium dioxide.

It is also known that L-ascorbic acid is unstable in these dosage forms. Specifically, increasing the level of L-ascorbic acid in the emulsion formulation may lead to instability. «Φ ···φφφφ·φφ φφφφφφφφφφφφφφφφφφφφφφφφφ

Ze · φ emul emul emul emul emul emul emul emul emul emul · · For example, an elevated level of ascorbic acid leads, for example, to the decomposition of L-ascorbic acid in an emulsion, giving the composition a yellowish to brownish color. Thus, it is desirable to stabilize this ascorbic acid composition especially when present in the emulsion at higher levels.

Some combination formulations have already been prepared to stabilize these ascorbic acid compositions. Japanese Published Application (Kokai) H-213212 Imamura et al., 1989 discloses stable cosmetic compositions containing ascorbic acid and gluconic acid derivatives. Japanese Published Application H-305009 Yamada et al., 1989 discloses stable cosmetic compositions containing ascorbic acid derivatives and cyclodextrin Published Japanese Application H3-63208 Sato et al., 1991 discloses compositions comprising ascorbic acid and phenoxethanol. These combinations ensure sufficient stability of the composition, but unfortunately the color change of the composition to yellowish or brownish is still noticeable, especially during prolonged storage.

Accordingly, there is a need to provide a stable skin lightening emulsion with an increased content of ascorbic acid and at the same time properties that do not impair the aesthetic impression of the product. No prior art document is able to provide the advantages and benefits described in the present invention.

SUMMARY OF THE INVENTION

The present invention describes oil-in-water emulsions comprising:

A. water-soluble ascorbic acid

B. metal oxide

C. structure-providing substance

D. hydrophobic component

E. a hydrophilic liquid carrier wherein the emulsion has a pH from about 6 to about 10.

These and other features, aspects, and advantages of the present invention will be better understood by reading the following description and the appended claims.

Since the description results in claims specifically claiming individual areas of the invention, it is likely that the present invention will be understood from the following description.

All percentages, ratios, and levels of the ingredients herein are based on the actual total amount of the composition unless otherwise indicated.

All measurements were performed at 25 ° C unless otherwise noted.

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All publications, patent applications, and patents cited herein are hereby incorporated by reference. Citation of any of the references does not mean that the prior art describes the subject matter of the present invention.

The term "containing" means that other steps and other ingredients that do not affect the overall result may also be added. The term also includes the terms "consisting of" and "consisting mainly of". The term "topical application" means that the composition is applied or applied to the skin surface.

The term "skin lightening" describes changing the appearance of the skin to brighter, lighter and / or whiter and affecting hyperpigmentation relative to prior treatment.

The term "cosmetically acceptable" means that the compositions or components thereof described herein are suitable for use in the treatment of human skin without undesirable toxicity, incompatibility, instability, allergic reactions and the like.

The term "safe and effective amount" describes an amount of a substance or composition sufficient to provide a benefit, in particular good skin appearance or feel, including the benefits described herein, but so low that there are no significant side effects, i.e. The composition provides a good risk-benefit balance at the discretion of the skilled artisan.

The term "mixtures" describes simple combinations of materials and any substances that may arise from their combination.

All ingredients, such as the active ingredients and other useful ingredients, can be divided or described according to their cosmetic and / or therapeutic benefit or effect. It will be appreciated that the active ingredients and other ingredients used herein, in some cases, provide more than merely cosmetic and / or therapeutic benefit or act in several different ways. Therefore, their classification, which is used, is for convenience only and cannot be taken as the limit of individual ingredients for a particular application or for several of the listed applications. The present invention describes oil-in-water emulsions comprising:

A. a water-soluble component containing ascorbic acid

B. metal oxide

C. structural component

D. hydrophobic component

E. hydrophilic liquid carrier

Suitably, the pH of the emulsion of the present invention is from about 6 to about 10, more preferably from about to about 9.

Without wishing to be bound by theory, it is believed that the high reducing capacity of water-soluble ascorbic acid improves cellular respiration, activates enzymes, and acts as an antioxidant.

Furthermore, it is believed that topical application of ascorbic acid results in a reduction of the oxidized complex of melanin and its precursors, as well as inhibition of the tyrosinase activity in melanosome. Accordingly, ascorbic acid compositions can improve skin properties by preventing melanin formation and reducing the appearance of liver spots and freckles associated with skin hyperpigmentation.

By increasing the concentration of ascorbic acid in the composition, the efficiency of the composition is usually increased. For example, increasing the amount of ascorbic acid in the skin lightening composition increases the skin lightening level. Unfortunately, in the past, it has been very difficult to increase the level of ascorbic acid in the formulation, as formulations with elevated levels of ascorbic acid, especially those in the form of an emulsion, become unstable, particularly with regard to the physical properties of the emulsion. . Fortunately, we have found that by adding the structural component to the emulsion, it is possible to maintain the original physical properties of the water-soluble ascorbic acid and thereby the emulsion as such, even when the composition contains relatively high levels of water-soluble ascorbic acid.

A. Water-soluble ascorbic acid

The oil-in-water emulsions of the present invention comprise water-soluble ascorbic acid. The water-soluble ascorbic acid is selected depending on its compatibility with the other ingredients. The water-soluble ascorbic acid may be added as a substantially pure material, for example, an extract obtained by suitable physical and / or chemical isolation methods from natural (eg, plant) sources.

The oil-in-water emulsions of the present invention typically comprise from about 1.0% to about 10.0% water-soluble ascorbic acid, more preferably from about 2.0% to about 5.0%.

The term "water-soluble ascorbic acid" describes ascorbic acid or its derivatives according to the general formula I:

A ^{R 1} wherein V and W are independently -OH, R ¹ is -CH (OH) -CH 2 OH and salts thereof.

(AND)

Suitably, the water-soluble ascorbic acid used herein is an ascorbic acid salt or derivative thereof, such as a non-toxic alkali metal salt, an alkaline earth metal salt, and an ammonium salt commonly known to those skilled in the art, which may be e.g. sodium, potassium, lithium, calcium, magnesium, barium, ammonium salts, which can be prepared using techniques known in the art. More preferably, the water-soluble salt of ascorbic acid used in the present invention is a metallic ascorbate according to the following general formula II:

xMI (Π)

Wherein R and R are independently hydrogen and linear or branched alkyl of from 1 to about 8 carbons, M1 is

More preferably, R and R are independently hydrogen and linear or branched alkyl is from 1 to about 3, M ¹ is sodium, potassium, magnesium or calcium.

Examples of other suitable water-soluble salts of ascorbic acid according to formula (II) are monovalent metal salts (eg sodium ascorbate, potassium ascorbate), divalent metal salts (magnesium ascorbate, calcium ascorbate) and trivalent metal salts (eg aluminum ascorbate) or ascorbic acid. It is preferred that the water-soluble salts of ascorbic acid of the present invention are water-soluble esters of ascorbyl according to the following general formula III:

ΆΟ CT (III)

wherein A is sulfate or phosphate, R ⁴ and R ⁵ are independently hydrogen and linear or branched alkyl of 1 to about 8 carbons, M ² is a metal ion and is in the range of 1 to 3. More preferably R ⁴ and R ⁵ are independently hydrogen and linear or branched alkyl of from 1 to about 3, M is sodium, potassium, magnesium or calcium.

· 99 · «99

9 9 9 9 9

9 9 9 9 9 9 9 99

9 9 9 9 9 9 9 9 99

99 99 99 99999

Examples of water-soluble salt derivatives are, for example, salts of L-ascorbyl phosphate esters such as sodium L-ascorbyl phosphate, potassium L-ascorbyl phosphate, magnesium L-ascorbyl phosphate, calcium L-ascorbyl phosphate, aluminum L-ascorbyl phosphate. Salts of L ascorbyl sulfate esters may also be used. Examples are L-ascorbyl sulfate, potassium L-ascorbyl sulfate, magnesium L-ascorbyl sulfate, calcium L-ascorbyl sulfate, aluminum L-ascorbyl sulfate.

B. Metal oxides

The oil-in-water emulsions of the present invention comprise metal oxides. The metal oxides useful in the present invention are present in the emulsion in amounts of from about 0.1% to about 5%, preferably from about 0.5% to about 2%. Suitable metal oxides are, for example, titanium dioxide, zinc oxide, zirconium oxide, alumina and combinations thereof (combinations being intended combinations of particles containing one or more of these materials as well as mixtures of these particulate materials), most preferably titanium dioxide. The metal oxides useful in the present invention are commercially available from a variety of sources. A suitable metal oxide is, for example, Tronox ™ (titanium dioxide) SAT-T CR837 (conventional titanium dioxide) available from US Cosmetics, titanium dioxide CR50 available from Ishihara Sangyo Kaisha, and titanium dioxide JA-1 available from Tayca Corporation.

C. Structural component

The water-oil emulsion of the present invention comprises a structural component. The term "structural component" as used herein describes a substance that forms an organized structure, a gel-like cross-linked structure in which both hydrophilic and hydrophobic components can then occur. This structural component is believed to provide good rheological properties of the composition. Which contribute to the stability of the emulsion. Preferably, the structural component is present in an amount of from about 1% to 10%, preferably from 2% to 8% of the composition.

Preferably, the structural component comprises a fatty alcohol and an amphiphilic surfactant. Regardless of theory, it is likely that the fatty alcohol, together with the amphiphilic surfactant, together form a lamellar structure, resulting in the maintenance of both phases, oil and water. It is also believed that these organized structures, referred to as "fatty alcohol gel cross-linking systems", contribute to emulsion stability.

The fatty alcohols are saturated, linear or branched fatty alcohols, which may be saturated, linear or branched C ₂ -3o fatty alcohols, saturated, linear or branched C12. Diols and mixtures thereof. The most suitable fatty alcohols are cetyl alcohol, stearyl alcohol and 99 99 9.

9 9 9 9 9 9 9 9 99

. 9 99 99999 99 9

9 9 9 9 9 9 9 9 9 9 9

9 9 9 9 9 9 9 9 9

99 99 99 99 999 mixtures thereof. Preferably, the fatty acids used herein are present in an amount of from about 1% to about 1% of the composition, more preferably from about 1% to about 5% of the composition.

The amphiphilic surfactant used in the present invention includes surfactants from a wide variety of non-polar, cationic, anionic, polar, amphoteric, as well as mixtures of these surfactants. Examples of the wide variety of other surfactants useful in the present invention are described in the book "Detergents and Emulsifiers", McCutcheon, North American Edition (1986), published by Allured Publishing Corporation, which is incorporated herein by reference. For further examples of useful surfactants, see U.S. Patent No. 4,800,197 to Kowcz et al., Jan. 24, 1989, which is incorporated herein by reference. Suitably, the useful amphiphilic surfactant is present in an amount of from 1% to about 10% of the composition, more preferably from about 2% to 6%.

A more preferred amphiphilic surfactant component of the present invention is a nonpolar surfactant. Most preferred non-polar surfactants are the condensation product of alkylene oxides with both fatty acids and fatty alcohols (i.e., where a portion of the polyalkylene oxidizes at one end with a fatty acid and at the other end attached via an ether linkage to a fatty alcohol). These materials have the general formula R ² CO (X ¹ ) _Z OR ³ , wherein R ² and R ³ are independently alkyl containing from about 10 to 30 carbons, X ¹ is derived from -OCH 2 CH 2, e.g., ethylene glycol or oxide or -O CH 2 The CH CH 3 - derived from propylene glycol or oxide az ranges from about 6 to about 100.

Other examples of these nonpolar surfactants are ceteth-6, ceteth-10, ceteth12, ceteareth-6, ceteareth-10, ceteareth-12, ceteareth-20, steareth-6, steareth-10, steareth-12, steareth-20, steareth-21, steareth-100, PEG-6 stearate, PEG-10 stearate, PEG-12 stearate, PEG-100 stearate, PEG-10 glyceryl stearate, PEG-20 glyceryl stearate, PEG-30 glyceryl cocoate, PEG-80 glyceryl cocoate, PEG- 80 glyceryl thalate, PEG-200 glyceryl thalate, PEG-8 dilaurate, PEG-10 distearate, glyceryl monostearate, glyceryl distearate, glyceryl monolaurate, glyceryl dilaurate and mixtures thereof.

The structural component may further comprise a thickener. Examples of useful thickeners useful in the present invention are polysaccharides and materials that are derived from natural sources such as tongs.

A large number of polysaccharides known in the art can be used. The term "polysaccharides" as used herein refers to a substance consisting of a spine containing a repeating sugar unit (a so-called carbohydrate). A non-limiting example of polysaccharides useful in the present invention may be, for example, cellulose, carboxymethylhydroxyethylcellulose,

Φ <9 cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethylethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylhydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate and mixtures thereof.

Additionally, alkyls substituted with celluloses are useful in the present invention. In these polymers, the hydroxy group of the cellulose polymer is hydroxyalkylated (preferably hydroxyethylated or hydroxypropyllated) to form a hydroxyalkylated cellulose that is further modified with C 10-30 linear or branched alkyl via an ether bond. These polymers are usually ethers of C10-30 linear or branched alcohols with hydroxyalkylcellulose. Examples of useful alkyl groups are, for example, stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, cocoyl (i.e., an alkyl group derived from coconut oil alcohols), palmityl, oleyl, linoleyl, linoenyl, ricinoleyl, behenyl, and mixtures thereof. Among these alkylhydroxyalkylcellulose ethers, the most preferred materials are CTFA designated cetylhydroxyethylcellulose, which are ethers of cetyl alcohol and hydroxyethylcellulose. These materials are sold under the trade name Natrosol® CS Plus from Aqualon Corporation.

Other useful polysaccharides are scleroglucans containing a linear chain (less than 3) of linked glucose units with less than 6 linked glucose for every three units, commercially available, e.g., as Clearogel ™ CS11 from Michel Mercier Products Inc. (Mountainside, N.J.).

Non-limiting examples of slugs are materials such as acacia, agar, alginic acid, alginic acid, ammonium alginate, calcium amylopectinalginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gelan glue, guar glue, hydroxypropyltrimonium guarate chloride, hectorite, hyaluronic acid, hyalurate hydroxypropylchitosan, hydroxypropylguarate, karaye, seaweed, natto, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotia, sodium carboxymethyldextran, sodium carrageenan, tragacanth, xanthan, and mixtures thereof.

D. Hydrophobic component

The hydrophobic component useful in the present invention may be a lipid, oil, oily, or other hydrophobic component. This hydrophobic component is used as a plasticizer. A variety of suitable hydrophobic agents can be used, as are well known in the art, and examples of such agents can be found in Sagarin, Cosmetics, Science and Technology, 2nd Edition, Volume 1, pp. 32-43 (1972). Non-limiting examples of suitable hydrophobic components are mineral oils, petroleum, C7.30 linear or branched hydrocarbons, Ci. _3O alcohol esters, glycerides, alkylene glycol esters, propoxylated and ethoxylated derivatives, sugar esters, vegetable oils, • 4 ·· 44 · · 44 ···· 44 * 44 · • 444 4 444 * · 4

44 444 44 444

4 4 4444 44

44 44 4 · ·· · hydrogenated vegetable oils, animal fats and oils, C4.20 alkyl ethers of polypropylene glycols, C1.20 esters of carboxylic acids of polypropylene glycols and di-C ₈ . ₃₀ alkyl ethers. Examples of useful hydrophobic components are set forth, for example, in U.S. Patent 5,306,514 to Letton et al. 1994, Gauge Index, 10th Edition, Chapter 7048, p. 1033 (1983) and International Cosmetic Ingredient Dictionary, 5th Edition, Volume 1, pp. 415-417 (1993).

The fatty acid sugar esters useful in the present invention are C 1-6. _3O monoesters or polyesters of sugars and one or more carboxylic acid groups, preferably sucrose polyesters wherein the degree of esterification is 7 to 8, and wherein the fatty acid group is _C8 mono- and / or di-unsaturated behenic acid, in molar ratio unsaturated: behenic 1: 7 to 3: 5, preferably an octaester of sucrose which contains about 7 behenic acid groups and about 1 oleic acid group per molecule, e.g., sucrose fatty acid ester from cotton seeds.

Suitably, the oil-in-water emulsions comprise from about 2% to about 20% of the hydrophobic component, more preferably from about 3% to about 10%. The hydrophobic component may be a substance derived from animals, plants or oil and may be natural or synthetic (i.e., man-made).

E. Hydrophilic liquid carrier

The oil-in-water emulsions of the present invention comprise a liquid hydrophilic carrier (HLC). The most suitable HLC may comprise a dermatologically acceptable, non-aqueous hydrophilic diluent. Non-limiting examples of this liquid carrier may be polyhydric alcohols such as low molecular weight monovalent alcohols (i.e., C 1g) and low molecular weight glycols and polyols such as propylene glygol, butylene glycol, hexylene glycol, dipropylene glycol, polyethylene glycol (e.g., 200-1000 g / mol) ), propylene glycol (e.g. having a molecular weight of 425 to 2025 g / mol), glycerol, 1,2,4-butanetriol, 1,2,6-hexanetriol, and combinations thereof.

The oil-in-water emulsions of the present invention should contain from about 60% to about 95.0% HLC, preferably from about 70.0% to about 85.0%. HLC includes water and one or more water-soluble or dispersible components. The actual amount of water in the dosage form may vary depending on the desired or selected components to be used.

The HLC may further comprise a pH adjuster. The term "pH adjuster" refers to any component that contributes to increasing or lowering the total pH of the composition of the present invention to an optimum pH that prevents the decomposition of the components (particularly ascorbic acid). The optimum pH is selected according to the ascorbic acid derivative used. E.g. if L-ascorbyl phosphate (MAP) is included in the composition, the optimum pH is about 7.0 to 8.0. Suitable pH-adjusting agents are acetic, phosphoric, citric, triethanolamine.

9 99

9 9

99

99 · ·

9

0 0 ·

99 and carbonic acid. The combination of the foregoing is mostly used to set a specific optimum pH for the emulsion. The total amount of weight of the pH controlling agent in the emulsion should be from 0.01% to about 5.0%, preferably from about 0.5% to about 2.0%.

F. Other active ingredients

The oil-in-water emulsions of the present invention may further comprise other active ingredients acting in different ways to enhance the effect of the ascorbic acid component and / or to provide other beneficial properties. Examples of such substances may be, for example, vitamin B3, antioxidants / free radical eliminators, anti-inflammatory agents, antimicrobial agents, radiation protectants and chelators.

(i) Vitamin B3 component: Vitamin B3 improves skin properties, in particular by improving skin nourishment, including suppressing signs of skin aging, in particular wrinkles and pores. Vitamin B3 is typically present in an amount of from about 0.01% to about 50%, preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 10%, and most preferably from about 1% up to about 5%.

The term "vitamin B3" describes a component of formula IV:

R (IV) wherein R is -CONH 2 (i.e. niacinamide), -COOH (i.e. nicotinic acid) or -CH 2 OH (i.e. nicotinyl alcohol), derivatives thereof and any salts of the above ingredients.

Examples of derivatives of the above-mentioned vitamin B3 variants are, for example, nicotinic acid esters, including nicotinic acid esters without vasodilating effects, nicotinic acid-derived amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide.

Suitable nicotinic acid esters are nicotinic acid esters containing from 1 to 22 carbons, preferably from 1 to 16 carbons, and most preferably alcohols containing from 1 to 6 carbons. These alcohols may be linear or branched, cyclic or non-cyclic, saturated or unsaturated (including aromatic) and substituted or unsubstituted. The most preferred esters are those without vasodilating effects. As used herein, the term "no vasodilating effects" means that the ester usually does not contribute to visible swelling after application to the skin (most populations do not expect visible swelling, although some components may cause vasodilation that is not apparent to the naked eye) ). Esters of acid

44 44 ·· 44

4 4 4 · 4

4 44 4 · 444 4 4 • 44 444 4

4444 4444 · 4

Nicotine without vasodilating effects are for example tocopherol nicotinate and inositol hexanicotinate, with tocopherol nicotinate being more suitable.

Other vitamin B3 derivatives are niacinamide derivatives resulting in the substitution of one or more amide groups by hydrogen. Non-limiting examples of these niacinamide derivatives useful in the present invention are nicotinic acid-derived amino acids, prepared, for example, by reacting activated nicotinic acid (i.e., nicotinic azide or nicotinyl chloride) with an amino acid and nicotinyl alcohol esters of organic carboxylic acids (i.e. from 1 to about 18 carbons). Specific examples of these derivatives are, for example, nicotinuric acid (CsHg ^ Ch) and nicotinylhydroxamic acid (C6H6N2O2), which have the following chemical structures:

Nicotinuric acid, according to formula V:

(V) nicotinylhydroxamic acid, according to formula VI:

(VI)

Examples of nicotinyl alcohol esters are, for example, nicotinylalcohol esters of carboxylic acids salicilic, acetic, glycolic, palmitic and the like. Other non-limiting examples of vitamin B3 derivatives useful in the present invention are 2-chloronicotinamide, 6-aminonicotinamide, 6-methylnicotinamide, n-methylnicotinamide, n, , n- (hydroxymethyl) -nicotinamide, quinolinic acid imide, nicotinanilide, n-benzylnicotinamide, n-ethylnicotinamide, nifenazole, nicotinaldehyde, isonicotinic acid, methyisnicotinic acid, thionicotinamide, nialamide, 1- (3-pyridymethyl) urea, mercapto-nicotinic, nicomol and niaprazine.

Non-limiting examples of the aforementioned vitamin B3 derivatives are well known in the art and commercially available from a variety of sources, e.g., Sigma Chemical Company (St.

3 «· *

St. Louis, MO), ICN Biomedicals, INC (Airvin, CA), and Aldrich Chemical Company (Milwaukee,

WI).

4 • 4

4 4

4 * 4

One or more vitamin B3 derivatives may be used in the present invention. The most suitable derivatives of vitamin B3 are niacinamide and tocopherol nicotinate. Nevertheless, niacinamide is most suitable.

When used, the salts, derivatives and derivatives of the salts of niacinamide are most suitable those having substantially the same efficacy as niacinamide in regulating the skin environment as described herein. Vitamin B3 salts are also useful in the present invention. Non-limiting examples of vitamin B3 salts useful in the present invention are organic or inorganic salts, which may be inorganic salts with non-ionic inorganic elements (e.g., chlorides, bromides, iodides, carbonates, preferably chlorides) and organic salts of carboxylic acids (including mono- , di- and tri-Cl-18 salts of carboxylic acids (e.g., acetate, salicylate, glycolate, lactate, malate, citrate, where the most suitable monocarboxylic acid salt is acetate). These and other salts of vitamin B3 may be prepared by those skilled in the art, for example, as described by W. Wenner, "The Reaction of L-Ascorbic and D-Iosascorbic Acid with Nicotinic Acid and Its Amide", J. Organic Chemistry, Vol. 14, 22-26 (1949). Wenner describes the synthesis of salts of niacinamide ascorbic acid. In the most suitable variant of the present invention, the nitrogen contained in the vitamin B3 cycle is chemically free (i.e. unbound and / or unattached) or becomes substantially chemically free upon entry into the skin ("chemically free" is further an alternative to the term "uncomplexed"). Preferably, the vitamin B3 component is completely uncomplexed. Accordingly, if the composition comprises vitamin B3 in the form of a salt or other complexed form, the complex should be substantially reversible, more preferably completely reversible under the conditions where the composition is applied to the skin. For example, the complex may be partially reversible at a pH of about 5.0 to about 6.0. This reversibility should be determined by one skilled in the art.

It is preferable that the vitamin B3 be substantially uncomplexable in the composition prior to application to the skin. An exemplary example for minimizing or completely preventing the formation of unwanted complexes is the elimination of materials that form essentially irreversible complexes with vitamin B3, substances affecting pH, ionic strength, surfactants and dosage forms, where vitamin B3 and the complexing materials are in different stages. These parameters always depend on the judgment of the person skilled in the art.

In a most preferred variant of the present invention, the vitamin B3 component comprises a limited amount of vitamin B3 salts, and most preferably no vitamin B3 salts. It is advisable to: · · · · · · · · · · · · · · · · · · · · · · · ·

9 9 Vitamin B3 component less than 50% of these salts, preferably if it contains essentially no salts. The vitamin B3 component of the compositions of the present invention should have a pH of from about 4 to about 7, and typically should contain less than 50% salts.

The vitamin B3 component may be used as a substantially pure material or as an extract obtained by suitable physical and / or chemical isolation from natural (eg, plant) sources. The vitamin B3 component should be essentially pure, preferably completely pure.

(ii) Antioxidants and free radical scavengers: antioxidants and free radical scavengers are used to provide UV protection, which can cause changes in roughness or texture in stratum corneum, and against other substances commonly found in the environment, can cause skin damage.

Antioxidants and free radical eliminators such as tocopherol (vitamin E), tocopherolsorbate, tocopherol acetate, other tocopherol esters, butylated hydroxybenzoic acid and its salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially available under the trade name Trolox ®), gallic acid and its alkyl esters, in particular propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, amines (i.e. N, N-diethylhydroxylamine, aminoguanidine), sulfhydryl-containing substances (e.g. glutathione ), dihydroxyfumaric acid and its salts, lysine piperolate, arginine piperolate, nordihydroguaiaretic acid, bioflavonoids, lysine, methionine, proline, superoxide dismutase, silymarin, tea extracts, grapefruit seed extract and bark extract, melanin, rosemary. The most suitable antioxidants and free radical eliminators are tocopherolsorbate and other tocopherol esters, most preferably tocopherolsorbate. An example of the use of tocopherlsorbate in topical formulations and its applicability in the present invention is described in U.S. Patent 4,847,071, Bisset et al., Jul. 11, 1989.

(iii) Anti-inflammatory ingredients: anti-inflammatory ingredients improve skin properties by, for example, achieving uniformity and acceptability of skin tone and / or color. Suitable anti-inflammatory agents are, for example, steroidal anti-inflammatory agents and non-steroidal anti-inflammatory agents. The most preferred steroidal anti-inflammatory agent is hydrocortisone. A variety of agents belonging to this group are known to those skilled in the art. For a detailed description of the chemical structure, synthesis, side effects, etc. of non-steroidal anti-inflammatory agents, see well known publications such as Antiinflammatory and Anti-Rheumatic Drugs, L. D. Rainsford, Vol. I-III, CRC Press, Boca Raton, (1985), and Anti-inflammatory Agents, Chemistry and Pharmacology, 1, R. A. Scherrer, et. al.,

Academic Press, New York (1974), which are incorporated herein by reference.

The so-called "natural" anti-inflammatory agents are also useful in the present invention. These substances can be obtained as extracts by appropriate physical and / or chemical isolation from natural sources (i.e. plants, fungi or microorganisms). Examples are alphabisabolol, aloe vera, Manistha (an extract from plants of the genus Rubia, in particular Rubia Cordifolia) and Guggal (an extract from plants of the genus Commiphora, in particular Commiphora Mukul), cola extract, chamomile extract, seaweed extract.

Other anti-inflammatory agents useful in the present invention are licorice substances (Glycyrrhiza Glabra plant) such as gylcylrhetic acid, glycylrhizic acid and derivatives thereof (e.g. salts and esters). Suitable esters of the above are metal salts and ammonium salts. Suitable esters are C2-24 saturated or unsaturated acid esters, preferably C10-24 and most preferably C16-24. (Iv) Antimicrobials: as used herein, the term "antimicrobials" describes substances capable of killing microbes, preventing microbial development, or preventing the pathogenic effect of microbes. Antimicrobial ingredients are useful, for example, for the control of acne. The most suitable antimicrobial ingredients useful in the present invention are benzoyl peroxide, erythromycin, tetracycline, clindamycin, azelaic acid, and irgasan ™ DP300 (Ciba Geigy Corp., USA). A safe and effective amount of an antimicrobial component, preferably from about 0.001% to about 10%, preferably from about 0.01% to 5%, preferably from about 0.05% to about 2%, is to be added to the composition of the present invention.

(v) Solar and UV filters: solar and UV filters protect the skin from extensive changes in shade and structure in the stratum corneum after exposure to ultraviolet light and can be added to the composition of the present invention. Suitable solar and UV filters may be organic or inorganic.

A variety of solar and UV filters are applicable to the present invention. See U.S. Patent 5,087,445 to Haffey et al., Feb. 11, 1992; U.S. Patent 5,073,372, Turner et al., Dec. 17, 1991; U.S. Patent 5,073,371, Turner et al., Dec. 17, 1991; and Segarin, et al, in chapter Vlil, p 189, Cosmetics Science and Technology (1972), which describes a number of suitable sun and UV filters. Among these solar and UV filters which are useful in the present invention are, for example, 2-ethylhexyl p-methoxycinamate (commercially available as PARSOL MCX), butylmethoxydibenzoyl methane, and the like. · · · · · · · · · · · · · · · · · · · · · · · · · · ·

2-hydroxy-4-methoxybenzophenone, 2-phenylbenzimidazole-5-sulfonic acid, octyldimethyl-p-aminobenzoic acid, octocrylene, 2-ethylhexyl N, N-dimethyl-p-aminobenzoate, p-aminobenzoic acid, 2-phenylbenzimidazole-5- sulfonic acid, octocrylene, oxybenzone, homomenthylsalicylate, octylsalicylate, 4,4'-methoxy-t-butyldibenzoylmethane, 4-isopropyldibenzoylmethane, 3-benzylidenefrene, 3- (4-methylbenzylidene) camphor, titanium dioxide, zinc oxide, silicon, silicon Eusolex ™ 6300, Octocrylene, Parsol 1789, and mixtures thereof. Furthermore, the sun and UV filters described in U.S. Patent No. 4,937,370 to Sabatelli, June 26, 1990, and U.S. Patent No. 4,999,186 to Sabatelli, March 12, 1991 are also partially useful in the composition of the present invention. described have two different chromophore groups in one molecule which exhibit different UV absorption spectra. One group of chromophores absorbs mainly in the UV-B region, while the other absorbs mainly in the UVA region. These sun and UV filters provide high efficiency, UV absorption in a wide area, low penetration rate and long lasting effect as opposed to commercial sun and UV filters.

The exact amount will then depend on the choice of filter and the desired protection factor (OF). The protective factor is the commonly used value of photo-protection against erythemia. See. Federal Register, Volume 43, Number 166, pp. 38206-38269, April 25, 1978.

Sun or UV sequins can also be added to improve the skin itself, in particular to increase its resistance to water washing or scuffing. The most suitable UV filters that provide these properties are copolymers of ethylene and acrylic acid. Compositions containing this copolymer are described in U.S. Patent 4,663,157, Brock, May 5, 1987.

(vi) Chelators: As used herein, the term "chelator" describes a substance that is capable of removing metal ions from the system by complexing such that metal ions cannot further enter or catalyze further chemical reactions. The use of a chelator is particularly important to provide protection against UV irradiation, which may contribute to widespread changes in the skin also against other substances present in the environment that may damage the skin.

Examples of chelators used in the present invention are disclosed in U.S. Patent No. 5,487,884 to Bissett et al., Jan. 30, 1996, PCT application 91/16035 and 91/16034 to Bush et al. 31 October 1995. Fluridioxime and its derivatives are the most suitable chelators.

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G. Other ingredients

In addition to the aforementioned active ingredients, the composition of the present invention may further comprise preservatives and enhancers, such as water-soluble or dissolved preservatives, e.g., Germall 115, methyl, ethyl, propyl and butyl esters of hydroxybenzoic acid, benzyl alcohol, EDTA, Bronopol (2-bromo-2-nitropropane-1,3-diol) and phenoxypropanol and other substances, such as skin emollients, which may be kojic acid, arbutin, WO95 / 23780, Kvalnes et al., September 8, 1995, nutrients skin, skin penetration enhancers, skin protectors, soothing agents, medicines, UV absorbers, uniform ingredients, chelators, anti-acne agents, anti-androgenic agents, depilators, keratolytic agents, panthenol-containing humectants such as is, for example, D-panthenol, a soluble or colloidal soluble humectant, such as hyaluronic acid and short chain sodium polyacrylates such as Sanwet ™ IM-1000, IM-1500, IM2500, available from Celanese Superabsorbent Materials, Portsmith, VA, and described in U.S. Patent 4,076,663, proteins and polypeptides and derivatives thereof, organic hydroxy acids, astringent drugs, topical analgesics, surface film forming agents, absorbents, including oil absorbents such as clays and polymeric absorbents, abrasives, anti-caking agents, anti-foaming agents, binding agents, biological additives, colorants, perfumes, essential oils and their solvents, natural extracts and collagen production stimulating agents.

H. Preparation of the composition

The oil-in-water emulsions of the present invention are usually prepared by any technique commonly used to prepare skin care compositions, i. oils which are well known in the art. These techniques typically involve admixing the ingredients in one or more steps to a relatively uniform state with or without heating, cooling, and the like. These techniques are described, for example, in Harry's Cosmeticology, 7th Ed., Harry & Wilkinson (Hill Publishers, London 1982).

EXAMPLES OF EMBODIMENTS OF THE INVENTION

The following examples further describe and demonstrate particular variations of the present invention. These examples are given by way of illustration only and should not be construed as limiting the present invention, as many changes are possible without departing from the scope of the present invention. As far as possible, all ingredients are given by chemical or CTFA names unless otherwise stated.

• · · · · * * * * *

EXAMPLE 1.

The composition below may be prepared by any method known in the art. Suitable methods are:

(Units%)

Chemical designation AND (B) C magnesium ascorbyl phosphate 3,000 - 2,000 sodium ascorbyl phosphate - 4,000 - titanium dioxide 2,000 0,000 1,000 stearyl alcohol 2,000 1,000 - cetyl alcohol 0.500 1,000 2,000 xanthan gum 0.100 0.020 - sugar fatty acid ester - 2,000 1,000 glycerol 5,000 7,000 9,000 glyceryl monostearate 3,000 2,000 4,000 Cetareth-10 0.400 - 0.400 Steareth-21 0.400 0.400 - Steareth-100 - 0.400 0.400 isononyl isononanoate 4,000 2,000 - izohexadekan - 2,000 4,000 sodium citrate 1,000 1,000 1,000 water add up to 100%

The oil-in-water emulsion described above is usually prepared as follows:

1) The water-soluble components, in addition to the water-soluble ascorbic acid and sodium citrate, are dissolved and the solution is heated to about 75 ° C.

2) Combine the separated aqueous solutions of ascorbic acid and sodium citrate and cool the mixture to below 40 ° C.

3) Mix (1) and (2) and maintain the temperature at approximately 75 ° C.

4) Heat the mixture of structural components and oil components to about 80 ° C.

5) Add mixture (4) to the aqueous phase (3) followed by high pressure homogenization.

6) Add titanium dioxide and glycerin to the mixture at about 30 ° C.

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The particular variant described in the above example has a number of advantages. For example, the above composition contains an elevated level of ascorbic acid to lighten the skin, exhibits improved aesthetic parameters such as product appearance, and prevents discoloration to yellow or brown even when stored for extended periods of time.

It is to be understood that the foregoing detailed description of the examples and particular variations of the present invention is given by way of illustration only, and that many modifications and variations will be apparent to those skilled in the art. within the scope of the appended claims.

Claims (10)

Λ # / PATENT CLAIMS An oil-in-water emulsion comprising: (a) from about 1.0% to about 10.0% of a water-soluble ascorbic acid component (b) a metal oxide (c) a structural component (d) a hydrophobic component (e) a hydrophilic liquid carrier, the emulsion having a pH of about 6 to about 10. 2. The oil-in-water emulsion of claim 1, wherein the emulsion comprises from about 0.1% to about 10% of the structural component. The oil-in-water emulsion of claim 2, wherein the structural component comprises a fatty alcohol and an amphiphilic surfactant. The oil-in-water emulsion of claim 3, wherein the emulsion comprises from about 0.1% to about 5% metal oxide. Oil-in-water emulsion according to claim 4, characterized in that the metal oxide is titanium dioxide, zinc oxide, zirconia, alumina and mixtures thereof. The oil-in-water emulsion of claim 1, wherein the structural component further comprises a thickener, which may be some of the pliers or polysaccharides. The oil-in-water emulsion of claim 6, wherein the thickener is a slurry. The oil-in-water emulsion of claim 1, wherein the emulsion comprises at least one additional active ingredient, which may be a vitamin B3 component, an antioxidant / radical eliminator, an anti-inflammatory agent, an antimicrobial agent, a sun and UV filter, and a chelating agent. An oil-in-water emulsion according to claim 1, characterized in that it comprises: (a) from about 2.0% to about 5.0% of a water-soluble ascorbic acid component (b) from about 0.5% to about 2.0% of a metal oxide (c) from about 2.0% to about 8% From about 2.0% to about 20.0% of the hydrophobic component (e) from about 60.0% to about 95.0% of the hydrophilic liquid carrier, the emulsion having a pH of from about 6 to about 20%; 10. 10. The oil-in-water emulsion of claim 9, wherein the emulsion comprises from about 1.0% to about 5.0% fatty alcohol and from about 2.0% to about 6.0% amphiphilic surfactant. .