KR20000052690A - Aqueous topical compositions comprising kojic acid, salicylic acid and a water soluble glycol ether - Google Patents

Abstract

PURPOSE: An aqueous topical compositions such as lotions, toners, and astringents comprising kojic acid, salicylic acid and a water soluble glycol ether is provided, which is useful for lightening of mammalian skin. CONSTITUTION: A aqueous topical composition for skin lightening comprises: (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: Rl-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 thickeners. The composition enhances the penetration of kojic acid to mammalian skin. By the excellent penetration effect of kojic acid to mammalian skin, the composition has excellent lightening effect for mammalian skin, yet requires lower levels of kojic acid than previously believed necessary. The reduced level of kojic acid results in a significant cost savings.

Description

Aqueous Topical COMPOSITIONS COMPRISING KOJIC ACID, SALICYLIC ACID AND A WATER SOLUBLE GLYCOL ETHER

Skin whitening is an important skin care especially needed for Asians. This includes basal skin tone and overall whitening of hyperpigmented lesions. In general, conditions leading to defects or absence of tyrosinase, an enzyme involved in melanin formation, are known to cause loss of pigmentation, for example albinism. Conversely, inhibition of tyrosinase is known to result in skin whitening by inhibition of melanogenesis. King, R. A. and Summers, C. G., Dermatologic Clinics, Vol. 6, pp. 217-227 (1988).

Tyrosinase is present in the melanosomes of epidermal melanocytes and promotes the formation of melanin from tyrosine. Goldsmith, L. A., Physiology, Biochemistry, and Molecular Biology of the Skin, Oxford University Press, pp. 873-903 (N.Y. 1991). The formation of melanin is reduced by binding the inhibitor to the active site of tyrosinase. See, generally, Prota, G., Melanins and Melanogeniesis, Academic Press, Inc., (San Diego 1992).

Certain tyrosinase inhibitors have been developed in the art. However, it is known in the art that the active ingredients of the compositions, especially for topical application (whether pharmaceutical or cosmetic), should be effective, biologically available and stable when exposed to light, air or skin. If the product is unstable, the degradation products of the active substance should be harmless.

One known tyrosinase inhibitor is kojic acid. Kojic acid is known to be very useful for topical skin lightening compositions. Unfortunately, Mt Koji is very expensive. In addition, kojic acid does not have a peeling effect.

One solution to adding a peeling effect to kojic acid is to add salicylic acid to the topical composition. Salicylic acid is commonly used in topical compositions because of the exfoliation effect. When salicylic acid is used in combination with kojic acid, the skin of a mammal is exfoliated to enhance the removal effect of skin pigmentation. Examples of such topical skin lightening compositions are described in Japanese Patent Laid-Open No. 95-300404. However, the cost of such compositions is very expensive mainly due to the amount and cost of kojic acid. Therefore, there is a need for an economical composition comprising kojic acid that effectively whitens mammalian skin.

Summary of the Invention

The present invention relates to (a) a safe effective amount of kojic acid, (b) a safe effective amount of salicylic acid, (c) water and (d) the general formula R ¹ -O-[(CH ₂ ) O _m ] _n H (wherein R ¹ Is an alkyl of 1 to 6 carbon atoms, m is about 2 to about 3 and n is about 1 to about 2) water-soluble glycol ethers comprising about 20 to about 30% (based on the weight of the composition) It relates to an aqueous topical composition for whitening, wherein the pH of the composition is from about 2.5 to about 4, and contains no thickener.

The composition of the present invention provides an aqueous topical composition containing no thickener, which is useful for whitening the skin of a mammal. The composition enhances the penetration of kojic acid into mammalian skin. Due to the good penetrating effect of kojic acid on mammalian skin, the composition exhibits an excellent off-white effect on the skin of mammals and requires less amount of kojic acid than previously thought necessary. The reduction of Mt. Koji saves a lot of money.

The present invention relates to aqueous topical compositions such as lotions, toners and astringents useful for skin whitening in mammals, including kojic acid, salicylic acid and water soluble glycol ethers.

Unless otherwise indicated, all percentages and ratios are by weight and all measurements are made at 25 ° C.

A. Kojisan

The composition of the present invention comprises a safe effective amount of kojic acid. Kojic acid is 5-hydroxy-2- (hydroxymethoxy) -4H-pyran-4-one and is a known active ingredient, Merck Index, 11th edition, p. 838 (1989). Koji-san has the following structure:

Kojic acid is used as a skin whitening ingredient that inhibits the formation of melanin. It is not economical if the composition contains more than about 3 weight percent kojic acid, and less than about 0.5 weight% of kojic acid is not expected to have a sufficient skin lightening effect. Typically, the compositions of the present invention comprise kojic acid at about 0.5 to about 3 weight percent of the composition, preferably about 1 to about 2 weight percent.

B. salicylic acid

The composition of the present invention comprises a safe effective amount of salicylic acid. Salicylic acid is a 2-hydroxybenzoic acid, a known active ingredient, Merck Index, 11th edition, p. 1324 (1989). Salicylic acid has the following structure:

Salicylic acid is used to exfoliate the mammal's skin and enhance the penetration of kojic acid into the mammal's skin. If the composition contains more salicylic acid than about 2% by weight of the composition, the irritation is caused. If salicylic acid is contained less than about 1% by weight of the composition, sufficient peeling effect and sufficient penetration improvement effect are not expected. Typically, the compositions of the present invention comprise salicylic acid at about 1% to about 2%, preferably about 1.2% to about 1.5% by weight of the composition.

C. water

The composition of the present invention comprises water. Water is used as the solvent. If the composition contains more than 78.5% by weight of the composition other components required for the present invention can not be included, and it is not economical to include water in less than about 40% by weight of the composition. Typically, the composition of the present invention comprises water in about 40 to 78.5% by weight, preferably about 45 to about 70% by weight of the composition.

D. Water Soluble Glycol Ether

The composition of the present invention comprises a water soluble glycol ether.

The water soluble glycol ether is of the general formula R ¹ -O-[(CH ₂ ) O _m ] _n H (wherein R ¹ is alkyl having 1 to 6 carbon atoms, m is about 2 to about 3, n is about 1 to about 2). Examples of alkyl groups R ¹ are the methyl, ethyl, propyl, butyl and hexyl groups. Glycol ethers having diethylene groups as alkylene groups and ethyl groups as alkyl moieties are diethylene glycol monoethyl ethers, and the CTFA (Cosmetic, Toiletry and Fragrance Association) name is ethoxydiglycol. Preferred water-soluble glycol ethers are diethylene glycol monoethyl ether, available under the tradename TRANSCUTOL from Gattefosse, France; Diethylene glycol monomethyl ether; And dipropylene glycol monomethyl ether, more preferred water soluble glycol ether is diethylene glycol monoethyl ether.

Water soluble glycol ethers are used as solvents of salicylic acid and to enhance the penetration of kojic acid into the skin of mammals. If the composition contains more than about 30% water soluble glycol ether, a sufficient penetration effect of kojic acid is not expected, and if the composition contains less than 20% water soluble glycol ether, salicylic acid cannot be dissolved.

Typically the water soluble glycol ether is included in the composition at about 20 to about 30 weight percent of the composition, preferably about 23 to about 27 weight percent.

E. Optional Ingredients

The aqueous topical compositions of the present invention may optionally include one or more components commonly used in such topical compositions. Examples of such optional ingredients are discussed in more detail below.

However, the absence of thickeners in the compositions of the present invention is an important aspect of the present invention, since the thickeners reduce the penetration effect of kojic acid into the skin of mammals. Thickener means a component generally used to increase the viscosity of a cosmetic. Thickeners include natural, semisynthetic and synthetic varieties. Natural thickeners include gum arabic, tragant, carrageenan, xanthan gum, gelatin and sodium chondroitin sulfate. Semisynthetic thickeners include methyl cellulose, carboxymethyl cellulose, sodium nitro cellulose, ethyl cellulose, hydroxy ethyl cellulose, hydroxy methyl cellulose, hydroxy propyl cellulose, rice starch, wheat starch, sodium alginate and propylene glycol alginate. Synthetic thickeners include polyvinyl alcohol, polyvinyl pyrrolidone, poly (vinyl acetate), sodium polyacrylate, polyacrylic resins, alkanolamine solutions, poly (ethyl methacrylate), carboxyvinyl polymers, poly (ethylene glycol ) And copolymers of polyoxyethylene and polyoxypropylene.

It is also an important aspect of the present invention that, after all optional ingredients have been added, the pH of the composition is preferably about 2.5 to about 4, preferably about 3 to about 4. If the pH is higher than 4, the desired exfoliation effect of salicylic acid and the desirable skin whitening effect of kojic acid cannot be expected, and if the pH is less than 2.5, it will cause skin damage.

Examples of optional compositions that may be used in the present invention are as follows.

1. a polyhydric alcohol and a lower alcohol having 1 to 3 carbon atoms

Polyhydric alcohols are used as moisturizers. If the composition contains more than about 15% polyhydric alcohol is not economical and there is a safety problem, if less than about 2% moisturizing effect is not expected.

The composition of the present invention may optionally comprise about 2 to about 15 weight percent of the composition, preferably about 3 to about 10 weight percent of a polyhydric alcohol such as propylene glycol, hexylene glycol, glycerin and propane diol. . Among the polyhydric alcohols, glycerin is preferred.

Lower alcohols having 1 to 3 carbon atoms may be used to impart a refreshing or cool sensation to the skin. If the composition contains more than about 15% lower alcohol, it will be irritating, and if the composition contains less than about 2% lower alcohol, no refreshing and cool sensory effect is expected.

The composition of the present invention may optionally comprise about 2 to about 15 weight percent of the composition, preferably about 3 to about 10 weight percent of lower alcohols having 1 to 3 carbon atoms, such as ethanol and isopropanol. Among lower alcohols having 1 to 3 carbon atoms, ethanol is preferred. Ethanol is preferably included when making a composition that imparts a refreshing or cool sensation to the skin. Such amounts of ethanol are expected to provide the skin with the desired freshness without irritating or excessively drying the skin.

2. Nonionic Surfactants

Nonionic surfactants are used to help dissolve the other components. If the composition contains more than about 5% of nonionic surfactant, it is not economical and there is a problem of stability. If the composition contains less than about 1% of nonionic surfactant, the effect of helping dissolution of other components is not expected. .

The composition of the present invention may optionally comprise about 1 to about 5 weight percent of the composition, preferably about 2 to about 4 weight percent of the nonionic surfactant. The nonionic surfactant acts as a co-solubilizing agent of salicylic acid, and when the same solvent is used, the amount of salicylic acid increases. Nonionic surfactants useful herein include known nonionic surfactants having a hydrophilic-lipophilic balance (HLB) of about 10 to about 18, preferably about 12 to 16.

Non-limiting examples of such nonionic surfactants are ethoxylated or propoxylated, preferably ethoxylated alcohols and alkyl phenols, with alcohol derivatives being preferred. In general, these alcohol derivatives contain straight or branched chain alkyl groups having 8 to 22 carbon atoms, preferably 10 to 20 carbon atoms, more preferably 12 to 20 carbon atoms, and generally about 6 to about 30 carbon atoms, preferably about It contains 8 to about 25 ethylene oxide or propylene oxide groups. Among these ethoxylated and propoxylated alcohols, ethoxylated derivatives are preferred.

Polyethylene oxide ethers derived from lauryl alcohol, cetyl alcohol, oleyl alcohol, stearyl alcohol, isocetyl alcohol, isostearyl alcohol or mixtures thereof are preferred for use herein. Most preferred for use herein is isocetyl ether (hereinafter referred to as isocetet 20) condensed with an average of 20 moles of ethylene oxide, known under the CTFA name isocetet 20.

3. Dialkylpolysiloxane-polyoxyalkylene copolymers

The composition of the present invention may optionally comprise a dialkylpolysiloxane-polyoxyalkylene copolymer. Such copolymers are expected to improve the overall skin sensation imparted by the composition and to reduce the irritation that may be caused by the components of the present invention. If the composition contains more than about 5% of the dialkylpolysiloxane-polyoxyalkylene copolymer, it is not economical and there is a problem of stability. If the composition contains less than about 1% of the dialkylpolysiloxane-polyoxyalkylene copolymer, the entire skin The improvement effect is not expected. The composition preferably comprises about 1 to about 5% of a dialkylpolysiloxane-polyoxyalkylene copolymer, most preferably about 2% to about 4% of a dialkylpolysiloxane-polyoxyalkylene copolymer.

Dialkylpolysiloxane-polyoxyalkylene copolymers useful herein include those that are soluble in water. Particularly useful are dimethylpolysiloxane-polyoxyalkylene copolymers (known as dimethicone copolyols) in which the polyoxyalkylene groups can be polyoxyethylene, polyoxypropylene groups or combinations thereof. The dimethylpolysiloxane moiety typically consists of 10 to about 30 units, preferably about 15 to 20 units. The polyalkylene moiety typically consists of 8 to about 12, preferably 10 to about 12 units.

4. Sunscreens, Conditioning Agents, Vitamins, Flavors, etc.

Depending on the needs of the product, the aqueous topical compositions of the present invention may include other optional ingredients. Non-limiting examples of such optional ingredients include additional water soluble surfactants that increase the solubility of the composition, water soluble ultraviolet and infrared block absorbers that block and absorb ultraviolet and infrared light, water soluble anti-inflammatory agents that reduce inflammation, inhibit oxidation and eliminate radicals Water soluble antioxidants / radical scavengers, water soluble chelating agents to chelate metals, water soluble skin conditioning agents to condition skin, preferred water soluble flavors, preferred water soluble dyes, water soluble vitamins to condition skin, condition skin There are water-soluble proteins to be skinned, water-soluble plant extracts to condition the skin, and water-soluble nutrients to condition the skin.

In order to prevent the composition comprising kojic acid from being colored, the composition of the present invention may include at least one anti-coloring agent selected from the group consisting of sodium metabisulfite, sodium bisulfide and sodium sulfite.

Various acids, bases, buffers and metal ion sequestrants can be used to control and / or maintain the pH and ionic strength of the compositions useful in the present invention. Materials useful for controlling and / or maintaining pH and / or ionic strength include sodium carbonate, sodium hydroxide, hydrochloric acid, phosphoric acid, sulfuric acid, acetic acid, sodium acetate, sodium hydrogen phosphate, sodium dihydrogen phosphate, citric acid, sodium citrate, sodium bicarbonate, Triethanolamine, EDTA (ethylenediaminetetraacetic acid), disodium EDTA, tetrasodium EDTA and the like.

Compositions of the present invention are typically formulated to have a pH of about 2.5 to about 4, preferably about 3 to about 4.

Aqueous topical compositions of the present invention include lotions, toners and astringents.

F. How to Whiten Mammal Skin

The present invention also relates to a method of whitening skin of a mammal comprising topical application of the skin lightening composition of the present invention. The amount and frequency of application of the active material can vary widely depending on the skin color already present in the subject, the darkness of the skin and the desired whitening.

Safely effective amounts of skin lightening agents in topical compositions generally range from about 1 mg to about 10 mg per cm 2 of skin at one application, preferably from about 2 mg to about 8 mg per cm 2 of skin at a single application, more preferably Is applied at about 3 mg to about 7 mg per cm 2 of skin, preferably from about 4 mg to about 5 mg per cm 2 of skin. The number of times of application is preferably about 4 to about 2 times a day, more preferably about 3 to about 1 time per day, and more preferably about 1 to about 2 times a day. . For lower animals, at least 5 days should be applied for skin whitening. In humans, at least one month should be applied to see the effect. If the whitening effect is present, the number of times and the amount of use can be reduced to the maintenance level in some cases. This level of maintenance varies from person to person, but if desired is preferably from about 1/10 to about 1/2, more preferably from about 1/5 to about 1/3 of the initial usage and / or frequency.

The following examples further describe and represent preferred embodiments that fall within the scope of the invention. The examples are provided for illustrative purposes only and should not be construed as limiting the invention as many variations may be made without departing from the spirit and scope of the invention. All percentages are by weight.

Examples 1-4

Example Compositions 1-4 are shown in Table 1 below.

The compositions shown in Table 1 can be prepared by conventional methods known in the art. Examples of suitable manufacturing methods that can be used are as follows.

Preparation method of Example 1

The salicylic acid and the transcutol are combined and heated to about 70-75 ° C. Separately, glycerin, sodium citrate, citric acid and water are mixed together to give aqueous phase-I. Water-I is mixed at about 70-75 ° C. The salicylic acid / transcutol mixture is then slowly added to aqueous phase-I and mixed at 75 ° C. for 30 minutes to give mixture-1. Kojic acid, sodium metabisulfite and water are mixed together to give aqueous phase-II. Water-II is mixed at 45 ° C. Water-II and D & C Yellow # 10 are added to Mixture-1 to obtain a lotion.

Preparation method of Example 2

The salicylic acid and the transcutol are combined and heated to about 70-75 ° C. Separately, sodium citrate, citric acid, isocetate 20 and water are mixed together to give aqueous phase-I. Water-I is mixed at about 70-75 ° C. The salicylic acid / transcutol mixture is then slowly added to aqueous phase-I and mixed at 75 ° C. for 30 minutes to give mixture-1. Kojic acid, sodium metabisulfite, dimethicone copolyol and water are mixed together to give aqueous phase-II. Water-II is mixed at 45 ° C. Water-II is added to mixture-1 to give a lotion.

Preparation Method of Example 3

The salicylic acid and the transcutol are combined and heated to about 70-75 ° C. Separately, glycerin, sodium citrate, citric acid, isocetate 20 and water are mixed together to give aqueous phase-I. Water-I is mixed at about 70-75 ° C. The salicylic acid / transcutol mixture is then slowly added to aqueous phase-I and mixed at 75 ° C. for 30 minutes to give mixture-1. Kojic acid, sodium metabisulfite, dimethicone copolyol and water are mixed together to give aqueous phase-II. Water-II is mixed at 45 ° C. Water-II and D & C Yellow # 10 are added to Mixture-1 to obtain a lotion.

Preparation Method of Example 4

The salicylic acid and the transcutol are combined and heated to about 70-75 ° C. Separately, glycerin, sodium citrate, citric acid, isocetate 20 and water are mixed together to give aqueous phase-I. Water-I is mixed at about 70-75 ° C. The salicylic acid / transcutol mixture is then slowly added to aqueous phase-I and mixed at 75 ° C. for 30 minutes to give mixture-1. Kojic acid, sodium metabisulfite, dimethicone copolyol and water are mixed together to give aqueous phase-II. Water-II is mixed at 45 ° C. Water-II is added to mixture-1 to give a lotion.

The compositions of the present invention have improved skin penetration enhancement effects of kojic acid as compared to compositions comprising thickeners and / or containing more than about 30% by weight of water soluble glycol ethers. Due to the strong skin penetration enhancing effect of kojic acid, a strong whitening effect of mammalian skin will be obtained by the composition of the present invention.

Example 5

This example describes a method of whitening the skin of a mammal using the composition of the present invention.

The composition of Example 1 is applied three times per day, 5 mg per 1 cm 2 of skin, once applied for one month. After one month, a significant skin whitening effect is seen. Once the desired level of skin whitening has been achieved, limit the treatment to maintain the whitening level.

The examples and embodiments described herein are for illustrative purposes only, and those skilled in the art may, in light of this, make various modifications or changes within the scope and spirit of the present application and the scope of the appended claims.

Claims (10)

(a) a safe effective amount of kojic acid, (b) a safe effective amount of salicylic acid, (c) water and (d) the general formula R ¹ -O-[(CH ₂ ) O _m ] _n H (wherein R ¹ represents 1 carbon atom). Alkyl of from 6 to 6, m is from about 2 to about 3, n is from about 1 to about 2) water soluble glycol ethers from about 20 to about 30% (based on the weight of the composition), pH of about 2.5 To about 4 and free of thickeners. The method of claim 1, About 3 weight percent of kojic acid in the composition; Salicylic acid, from about 1 to about 2 weight percent of the composition; And about 40-78.5 weight percent water of the composition. The method of claim 1, Kojic acid, in about 1 to 2% by weight of the composition; Salicylic acid, from about 1.2 to about 1.5 weight percent of the composition; And about 40-78.5 weight percent water of the composition. The method of claim 1, (a) about 1 to 2 weight percent of kojic acid in the composition; (b) about 1.2 to about 1.5 weight percent salicylic acid of the composition; (c) about 40-78.5 weight percent water of the composition; And (d) from about 23 to about 27 weight percent of a water soluble glycol ether of the composition, wherein the pH is from about 3 to about 4. The method of claim 4, wherein An aqueous topical composition wherein the water soluble glycol ether is diethylene glycol monoethyl ether. The method of claim 4, wherein An aqueous topical composition that is a lotion. The method of claim 4, wherein An aqueous topical composition further comprising at least one anti-pigmentant selected from the group consisting of sodium metabisulfite, sodium bisulfite and sodium sulfite. A method of whitening the skin of a mammal comprising topical application of the aqueous topical composition of claim 1 to the skin. A method of whitening skin of a mammal comprising topical application of the aqueous topical composition of claim 4 to the skin. A method of enhancing penetration of kojic acid into mammalian skin, comprising topical application of the aqueous topical composition of claim 4 to the skin.