MXPA99003846A

MXPA99003846A - Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether

Info

Publication number: MXPA99003846A
Application number: MXPA/A/1999/003846A
Authority: MX
Inventors: Sakoda Takayoshi; Toyama Kazumi
Original assignee: Sakoda Takayoshi; The Procter & Gamble Company; Toyama Kazumi
Filing date: 1999-04-23
Publication date: 1999-10-14

Abstract

Disclosed is an aqueous topical composition for skin lightening comprising:(a) a safe and effective amount of kojic acid, (b) a safe and effective amount of salicylic acid, (c) water, and (d) from about 20%to about 30%by weight of the composition, of a water soluble glycol ether of the general formula R1-O-[(CH2)mO]nH;wherein R1 is an alkyl of 1 to 6 carbon atoms, m is from about 2 to about 3, and n is from about 1 to about 2;wherein said composition has a pH from about 2.5 to about 4, and is absent of a thickener. Also disclosed is a method for lightening mammalian skin comprising topically applying to the skin said aqueous topical composition.

Description

TOPICAL AQUEOUS COMPOSITIONS CONTAINING KOCHIC ACID. ACIDO SALICILICQ AND AN ETHER GLICOLICQ SOLUBLE N AGUA TECHNICAL FIELD The present invention relates to aqueous topical compositions such as lotions, toners and astringents containing kojic acid and a water soluble glycol ether which are useful for lightening the skin of a mammal.

BACKGROUND OF THE INVENTION Skin lightening is an important need in skin care, especially in the Asian population. This includes the total clearance of the basic tone of the skin and hyperpigmented lesions. It is generally known that diseases resulting in defective or lacking tyrosinase, an enzyme involved in the formation of melanin, lead to a loss of pigmentation, ie albinism. Contrarily, it is known that the inhibition of tyrosinase leads to skin clearance through the inhibition of melanogenesis. See King, R. A. and C. G. Summers, Dermatoloaic Clinics, Vol. 6 pp. 217-227 (1988). Tyrosinase is present within the melanosomes in epidermal melanocytes and catalyzes the formation of melanin from tyrosine.

See Goldsmith, L.A., Phvsioloav. Biochemistrv. and Molecular Bioloav of the Skin Oxford University Press, pp. L873-903 (N.Y. 1991). The adhesion of an inhibitor to the active site of tyrosinase results in a decreased formation of melanin.

See generally Prota, G. Melanisn and Melanoaenesis. Academic Press, Inc., (San Diego 1992). The technique has produced certain tyrosinase inhibitors. However, it is well recognized in the art that any active in any composition, especially when used for topical application (either for pharmaceutical or cosmetic purposes) must be effective, bioavailable, stable when exposed to light, air or skin. . In case the product is unstable, the decomposition products of the asset must be harmless. A known inhibitor of tyrosinase is kojic acid. Kojic acid has been found to be quite useful for topical skin lightening compositions. Unfortunately, kojic acid is quite expensive. In addition, kojic acid does not have an exfoliation effect. One solution to add exfoliation effect on kojic acid is the addition of salicylic acid to the topical composition. Salicylic acid is commonly used in topical compositions because of its exfoliation effects. When combined with kojic acid, salicylic acid exfoliates the skin of the mammal resulting in an enhanced skin pigmentation removal effect. An example of such a topical skin lightening composition is found in Japanese open patent application (KOKAI) No. 7-300404. The cost of such composition, however, is still quite high due to mainly to the quantity and cost of kojic acid. Consequently, there is a need for an inexpensive composition containing kojic acid which effectively lightens the skin of the mammal.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to an aqueous topical composition for lightening the skin consisting of: (a) a safe and effective amount of kojic acid (b) a safe and effective amount of salicylic acid (c) water, and (d) 20% to 30% by weight of the composition, of a water-soluble glycol ether of the general formula R1-0 - [(CH2) mO] nH; wherein R1 is an alkyl of 1 to 6 carbon atoms, m is 2 to 3, and n is 1 to 2; wherein said composition has a pH of 2.5 to 4, and is absent from thickeners. The composition of the present invention provides an aqueous topical composition without oiler that is useful for lightening the skin of a mammal. The composition improves the penetration of kojic acid into the skin of the mammal. Because of the excellent penetration effect of kojic acid to the skin of the mammal, the composition has excellent lightening effect for the skin of the mammal, however it requires lower levels of kojic acid than previously believed necessary. The reduced level of kojic acid results in significant cost savings.

DETAILED DESCRIPTION All percentages and ratios are based on weight, and all measurements are conducted at 25 ° C, unless otherwise specified.

A. Koiic acid The composition of the present invention comprises a safe and effective amount of kojic acid. Kojic acid which is 5-hydrosi-2- (hydroxymethyl) -4H-pyran-4-one is a well-known active component and is described in the Merck index, eleventh edition, page 838 (1989). The structure of kojic acid is as follows Kojic acid is used as a skin lightening ingredient to inhibit the formation of melanin. If the composition contains more than 3% by weight of the composition, of kojic acid, it is not economical, and if it contains less than 0.5% by weight of the composition, of kojic acid, a sufficient explanatory effect of the skin is not expected. Typically, the composition of the present invention it contains from 0.5% to 3%, preferably from 1% to 2% by weight of the composition, of kojic acid.

B. Salicylic acid The composition of the present invention contains a safe and effective amount of salicylic acid. Salicylic acid which is 2-hydroxybenzoic acid is a well-known active component and is described in the Merck index, eleventh edition, page 1324 (1989). The structure of salicylic acid is as follows Salicylic acid is used to exfoliate mammalian skin and to improve the penetration of kojic acid to mammalian skin. If the composition contains more than 2% by weight of the composition, of salicylic acid, it will cause irritation, and if it contains less than 1% by weight of the composition, of salicylic acid, a sufficient effect of exfoliation and an improved effect is not expected. Enough of penetration. Typically, the composition of the present invention contains from 1% to 2%, preferably from 1.2% to 1.5% by weight of the composition, of salicylic acid.

C. Aqua The composition of the present invention contains water. Water is used as a solvent. If the composition contains more than 78.5% by weight of the composition, of water, other ingredients that are required in the present invention can not be included, if the composition contains less than 40% by weight of the composition, of water, it is not economic Typically, the composition of the present invention contains from 40% to 78.5%, preferably from 45% to 70% by weight of the composition, of water.

D. Qlicolic acid soluble in water. The composition of the present invention contains glycolic ether soluble in water The water soluble glycolic ether can be characterized by the general formula: R1 -? - [(CH2) mO] nH; wherein R is an alkyl of 1 to 6 carbon atoms, m is 2 to 3, and n is 1 to 2. Examples of the alkyl group R1 include methyl, ethyl, propyl, butyl and exo groups. This glycol ether having a diethylene group as the alkylene group and the ethyl group as the alkyl portion is diethylene glycol monoethyl ether to which the designation by CTFA (The Cosmetc. Toiletry and Fragrance Association) of ethoxydiglycol has been given. The preferred water soluble glycol ether is diethylene glycol monoethyl ether which is commercially available under the tradename TRANSCUTOL from Gattefosse, France; diethylene glycol monomethyl ether, and dipropylene glycol ether monomethyl and the most preferred water soluble glycol ether is the diethylene glycol monoethyl ether. The water soluble glycol ether is used as a salicylic acid solvent and to aid in improving the penetration of kojic acid into the skin of the mammal. If the composition contains more than 30% glycolic ether soluble in water, a sufficient effect of kojic acid penetration is not expected, is not sufficiently smooth to the skin and is not economical, and if the composition contains less than 20% ether glycolic soluble in water, salicylic acid can not be dissolved in this. Typically the water-soluble glycol ether is included in the composition in amounts of 20% to 30%, preferably 23% to 27% by weight of the water-soluble glycol ether composition.

E. Optional Components The aqueous topical composition of the present invention may optionally contain one or more components that are commonly used in such topical compositions. Examples of such optional components are discussed in more detail below. However, it is an important aspect of the invention that thickeners are not present in the composition because they decrease the penetration effect of kojic acid to mammalian skin. Thickeners mean ingredients that are commonly used to increase the viscosity of cosmetics. Thickeners include natural, semi-synthetic and synthetic Natural thickeners include gum arabic, tragacanth, Cartagena, xanthan gum, gelatin and sodium chondroitin sulfate. Semisynthetic thickeners include methyl cellulose, carboxymethyl cellulose, sodium nitro cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, rice starch, wheat starch, sodium alginate and propylene glycol alginate. Synthetic thickeners include polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl acetate), sodium polyacrylate, polyacrylic resin, alkanolamine solution, poly (ethyl methacrylate), carboxyvinyl polymer, poly (ethylene glycol) and polyoxyethylene and polyoxypropylene copolymer. It is also an important aspect of the invention that after all the optional components are added, the composition preferably has a pH of 2.5 to 4, preferably a pH of 3 to 4. If the pH is more than 4, the effect of Preferred exfoliation of salicylic acid and the skin-lightening effect preferred of kojic acid can not be expected, and if the pH is less than 2.5, it will cause damage to the skin. Examples of optional components that may be used in the present invention include the following: 1. - Polyhydric alcohol and lower alcohols that have 1 to 3 carbons Polyhydric alcohol is used as a humectant. If the composition contains more than 15% hydrochloric acid, it is not economical, and causes safety problems, and if it contains less than 2%, the moisturizing effect is not expected. The compositions of this invention may optionally contain from 2% to 15%, preferably from 3% to 10% by weight of the composition, of polyhydric alcohols such as propylene glycol, exylene glycol, glycerin and diol propane. Among the polyhydric alcohols, glycerin is preferred. Lower alcohols having 1 to 3 carbons can be used to impart a cooling or cold feeling to the skin. If the composition contains more than 15% of the lower alcohols, it will cause irritation, and if the composition contains less than 2% of the lower alcohols, the effect of refreshing and cold feeling to the skin is not expected. Compositions of this invention may optionally contain from 2% to 15%, preferably from 3% to 10% by weight of the composition, of lower alcohols having from 1 to 3 carbons such as ethanol and isopropanol. Among alcohols having 1 to 3 carbons, ethanol is preferred. Ethanol is preferably compressed by making compositions that are designed to impart a cool or cool feeling to the skin. It is known that the ethanol in the compositions helps to improve the solubility of the salicylic acid. This level of ethanol is expected to provide the desired refreshing sensation to the skin without being irritating or excessively drying the skin. 2. Nonionic Surfactant The nonionic surfactant is used to help dissolve other ingredients. If the composition contains more than 5% nonionic surfactant, it is not economical and can cause safety problems, and if it contains less than 1% nonionic surfactant, the effect to help dissolve other ingredients is not expected. The compositions of this invention may optionally contain from 1% to 5%, preferably from 2% to 4% by weight of the composition, of a nonionic surfactant. The nonionic surfactant acts as a co-solubilizer of salicylic acid, thereby allowing a higher level of salicylic acid when the same solvent is used. The nonionic surfactants useful herein include any of the well known non-ionic surfactants having an HLP (hydrophilic-lipophilic balance) of 10 to 18, preferably 12 to 16. Non-limiting examples of these surfactants are not Ionic are ethoxylated or propoxylated alcohols and alkylphenols, preferably ethoxylated with preferred alcohol derivatives. In general, these alcohol derivatives contain a straight or branched chain alkyl group having 8-22 carbons, preferably 10-20 carbons, more preferably 12-20 carbons, and generally contain from 6 to 30, preferably from 8 to 25, ethylene oxide or propylene oxide groups. Among these ethoxylated and propoxylated alcohols, the ethoxylated derivatives are preferred. Preferred for use herein are the polyletylene oxide ethers derived from lauryl alcohol, cetyl alcohol, oleyl alcohol, stearyl alcohol, isocetyl or isostearyl alcohol, and mixtures thereof. Most preferred for use herein is condensed isocetyl ether with an average of 20 moles of ethylene oxide, known by the designation CTFA as Isoceteth 20 (hereinafter called Isocetech 20) 3. Dialkyl polysiloxane-polyoxyalkylene copolymer The compositions of this invention may optionally contain a dialkyl polysiloxane-polyoxyalkylene copolymer. Such a copolymer is expected to improve the overall skin feel imparted by the composition and reduce any irritation that could be caused by a component of the present invention. If the composition contains more than 5% dialkyl polysiloxane-polyoxyalkylene copolymer, it is not economical and can cause safety problems, and if it contains less than 1% dialkyl polysiloxane-polyoxyalkylene copolymer, the effect of improving the skin feel is not expected. The composition preferably contains from 1% to 5% of dialkylpolysiloxane-polyoxyalkylene copolymer, more preferably from 2% to 4% of dialkylpolysiloxane-polyoxyalkylene copolymer. The dialkylpolysiloxane-polyoxyalkylene copolymers useful herein include those which are soluble in water. The copolymers dimethylpolysiloxane-polyoxyalkylene, known as dimethicone copolyols wherein the polyoxyalkylene group can be a polyoxyethylene group or polyoxypropylene group or a combination of both, are particularly useful. The dimethylpolysiloxane portion is typically made from 10 to 30 units, preferably from 15 to 2 units. The polyalkylene portion is typically made from 8 to 12, preferably from 10 to 12 units. 4. Sun filters, conditioning agents, vitamins, perfumes, etc. Other optional components may be included in the aqueous topical compositions of the present invention, depending on the needs of the product. Non-limiting examples of such optional components include additional water soluble surfactants to aid in the solubility of the composition, ultraviolet and infrared water soluble sun filters and absorbing agents for filtering and absorbing, ultraviolet and infrared, water soluble anti-inflammatory agents for reduce inflammation, water soluble agents antioxidants / radical scavengers to control oxidation and radical scavenging, water-soluble chelating agents to chelate metal, water-soluble skin conditioning agents to condition skin, water-soluble perfume for preference, color water-soluble for preference, water-soluble pH adjusters for adjusting the pH, water-soluble dyes for preference, water-soluble vitamins for conditioning the skin, water-soluble proteins for conditioning skin, water-soluble plant extracts to condition the skin, and water-soluble nutrients to condition the skin. In order to prevent the composition containing kojic acid from being colored, a composition of the present invention can include at least one anti-colorant agent selected from the group consisting of sodium metabisulfite, sodium bisulfite and sodium suifite. A wide variety of acids, bases, regulators, and sequestrants can be used to adjust and / or maintain the pH and ionic strength of the compositions useful in the present invention. Useful materials for adjusting and / or maintaining the pH and / or ionic strength include sodium carbonate, sodium hydroxide, hydrochloric acid, phosphoric acid, sulfuric acid, acetic acid, sodium acetate, sodium hydrogen phosphate, phosphate sodium dihydrogen, citric acid, sodium citrate, sodium bicarbonate, triethanolamine, EDTA (ethylenediaminetetraacetic acid), disodium EDTA, tetrasodium EDTA, and the like. The compositions of the present invention are typically formulated to have a pH of 2.5 to 4, preferably a pH of 3 to 4. The aqueous topical compositions of the present invention include lotions, bronzers and astringents.

F. Methods for lightening the skin in mammals The present invention also relates to methods for lightening the skin in mammals comprising the topical application of the skin lightening composition of the present invention. The amount of active agent and the frequency of application will vary widely depending on the color of the skin already in existence in the subject, the additional darkening rate of the skin, and the level of clearance desired. A safe and effective amount of skin lightening agent in a topical composition is applied, generally from 1 mg to 10 mg per cm2 of skin per application, preferably from 2 mg to 8 mg / cm2 of skin per application, more preferably 3 mg at 7 mg / cm2 of skin, also preferably 4 mg a mg / cm2 of skin. The application preferably ranges from four times a day to twice a week, more preferably from 3 times a day to once every third day, more preferably from once a day to twice a day. At least five days is required to see a skin lightening effect on lower animals. The application of for at least one month is required to see an effect on humans. After clarification is achieved, the frequency and dosage can be reduced to a maintenance level, as desired. Such maintenance varies according to the individual, but is preferably 1/10 to 1/2, more preferably 1/5 to 1/3 of the original dose and / or frequency, as needed.

The following examples further describe and demonstrate the preferred embodiments within the scope of the present invention. The examples are given only for purposes of illustration, and should not be considered as limitations of the present invention because many variations thereof are possible without departing from their spirit and scope.

G. Examples The following examples further describe and demonstrate embodiments within the scope of the present invention. The examples are given only for the purpose of illustration and are not intended as limitations of the present invention, since many variations thereof are possible without departing from the spirit and scope of the invention. All percentages are based on weight. The compositions of Examples Nos. 1-4 are shown in Table 1, below.

TABLE 1 (Quantity in percentage of weight) Component No.1 No.2 No.3 No »4 Kojic acid 1 1 1.5 2 Salicylic acid 1.5 1.2 1.5 1.5 TRANSCUTOL * 2.5 23 25 27 TABLE 1 (CONTINUED) Sodium citrate 4.5 3 4.5 4.5 Citric acid 6 4 6 6 Glycerin 3 0 3 5 Sodium metabisulfite 0.25 0.25 0.25 0.25 0. 01% D &C yellow # 10 0.3 0 0.03 0 Isoceteth 20 0 1 3 4 Copoiiol of dimethicone 0 1 3 4 Water c.s. at 100 c.s to 100 c.s to 100 c.s to 100 PH 3.4 3-4 3-4 3-4 TRANSCUTOL is diethylene glycol monoethyl ether which is commercially available from Gattefosse, France. The compositions shown in Table 1 can be prepared by any conventional method well known in the art. An example of a suitable preparation method that can be used is described as follows: Method of preparation of example No.1 The salicylic acid and TRANSCUTOL are combined and heated to 70-75 ° C. Separately, glycine, sodium citrate, citric acid and water are Mix together to obtain the water phase I. The water phase I is also mixed at 70-75 ° C. The TRANSCUTOL salicylic acid mixture is then slowly added to water phase I and mixed at 75 ° C for 30 minutes to obtain mixture I. Kojic acid, sodium metabilsulfite and water are mixed together to obtain the water phase II. The water phase II is also mixed at 45 ° C. Then water phase II and yellow D &C # 10 are also added to mixture I to obtain a lotion.

Method of preparation of example No.2 Salicylic acid and TRANSCUTOL are combined and heated to 70-75 ° C. Separately, sodium citrate, citric acid, Isoceteth 20 and water are mixed together to obtain the water phase I. The water phase I is also mixed at 70-78 ° C. The salicylic acid / TRANSCUTOL mixture is then slowly added to the water phase I and mixed at 75 ° C for 30 minutes to obtain a lotion.

The kojic acid, sodium metabilsulfite, dimethicone copolyol and water are mixed together to obtain the water phase II. The water phase II is also mixed at 45 ° C. Then the water phase II is also added to the mixture I to obtain a lotion.

Method of preparation of Example No.3 Salicylic acid and TRANSCUTOL are combined and heated to 70-75 ° C. Separately, glycerin, sodium citrate, citric acid, Isocetech 20 and water are mixed together to obtain the water phase I. The water phase I is also mixed at 70-75 ° C. The mixture of salicylic acid / TRANSCUTOL is then slowly added to the water phase I and mixed at 75 ° C for 30 minutes to obtain mixture 1. Kojic acid, sodium metabilsulfite, dimethicone copolyol and water are mixed together to obtain the water phase II. The water phase II is also mixed at 45 ° C. Then water phase II and yellow D &C # 10 are also added to mixture I to obtain a lotion.

Method of preparation of example No.4 Salicylic acid and TRANSCUTOL are combined and heated to 70-75 ° C. Separately, glycerin, sodium citrate, citric acid, Isoceteth 20 and water are mixed together to obtain the water phase I. The water phase I is also mixed at 70-75 ° C. The mixture of salicylic acid / TFtANSCUTOL is then added slowly to the water phase I and mixed at 75 ° C for 30 minutes to obtain the mixture I. Kojic acid, sodium metabiisulfite, dimethicone copolyol and water are mixed together to obtain the water phase II. The water phase II is also mixed at 45 ° C. Then the water phase II is also added to the mixture I to obtain a lotion. The compositions of the present invention have an improved skin penetration effect of kojic acid compared to thickener-containing compositions and / or contain more than 30% by weight of the composition of glycolic ether soluble in water. A strong lightening effect of mammalian skin will be obtained by the compositions of the present invention, due to the improved effect resulting from strong skin penetration of kojic acid.

EXAMPLE NO. 5 This example discloses a method for lightening mammalian skin using a composition of the present invention. The composition of Example 1 is applied at 5 mg / cm2 of skin per application three times a day for one month. After a month you see a significant effect of skin lightening. Once the desired level of skin lightening is achieved, the treatment is reduced to limit to one day, to maintain the level of clearance. It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light of them will be suggested to one skilled in the art and are to be included in the spirit and scope of this application and scope of the appended claims.

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - An aqueous topical composition for skin lightening comprising: (a) a safe and effective amount of kojic acid, (b) a safe and effective amount of salicylic acid, (c) water, and (d) from 20% to 30%. % by weight of the composition, of a water-soluble glycol ether of the general formula: R1-0 - [(CH2) mO] nH; wherein R1 is an alkyl of 1 to 6 carbon atoms, m is 2 to 3, and n is 1 to 2; wherein said composition has a PH of 2.5 to 4, and is absent from a thickener.

2. The aqueous topical composition according to claim 1, further characterized in that it contains from 0.5% to 3% by weight of the composition, of kojic acid; from 1% to 2% by weight of the composition, of salicylic acid; and from 40% to 78.5% by weight of the composition, of water.

3. The aqueous topical composition according to claim 1, further characterized in that it contains from 1% to 2% by weight of the composition, of kojic acid; from 1.2% to 1.5% by weight of the composition, of salicylic acid; and from 40% to 78.5% by weight of the water composition.

4. The aqueous topical composition according to claim 1, comprising: (a) from 1% to 2% by weight of the composition, of kojic acid; (b) from 1.2% to 1.5% by weight of the salicylic acid composition; (c) from 40% to 78.5% by weight of the composition, of water; and (d) from 23% to 27% in weight of the composition, of glycolic ether soluble in water wherein said composition has a pH of 3 to 4.

5. The aqueous topical composition according to claim 4, further characterized in that the glycolic ether soluble in water is diethylene glycol ether monoethyl.

6. The aqueous topical composition according to claim 4, further characterized in that the aqueous topical composition is a lotion.

7. The aqueous topical composition according to claim 4, further characterized in that it additionally contains at least one anti-color agent selected from the group consisting of sodium metabisulphite, sodium bisulfite and sodium sulfite.

8. A method for rinsing the skin of a mammal comprising topically applying to the skin said aqueous topical composition according to claim 1.

9. A method for rinsing the skin of a mammal comprising topically applying to the skin the aqueous topical composition according to claim 4.

10. A method for improving the penetration of kojic acid into the skin of a mammal comprising topically applying to the skin the topical aqueous composition according to claim 4.