JP2564690B2 - Topical agent for suppressing melanin production - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention relates to an external preparation for suppressing melanin production, which is incorporated into a cosmetic base or an ointment and exhibits an excellent whitening effect or sun protection effect. .

[Conventional technology]

Melanin is present in the skin in the form of brown to black eumelanin or yellow to red pheomelanin, and has the role of protecting the body from the harmful effects of ultraviolet light.
It is an important factor indispensable to the human body, but on the other hand,
It is known that when this melanin is unevenly and excessively produced on the skin surface, it causes liver spots (spots) and freckles (freckles).

Therefore, the present applicant has proposed that cosmetics and ointments that suppress the production of melanin and have the purpose of a whitening effect have been developed for a long time, and that kojic acid or its ester is excellent as an external preparation for suppressing melanin production. (JP-A-53-18739, JP-A-56-7776, JP-A-56-79616, JP-A-59-33207, etc.).

These kojic acids or their esters have the effect of suppressing the activity of tyrosinase, which is oxygen that converts tyrosine to dopa and dopa to dopaquinone, in the mechanism of melanin production, and as a result, suppresses the production of melanin. Is.

Furthermore, the present inventors have developed a drug that suppresses intracellular production of tyrosinase pigment cells, which contains one or more compounds selected from acetic acid, lactic acid, and viruvic acid as active ingredients. It is disclosed in Japanese Patent Publication No.-305025.

[Problems to be Solved by the Invention]

The acetic acid, lactic acid, and viruvic acid proposed by the present inventors and disclosed in the above-mentioned Japanese Patent Laid-Open No. 1-305025 include acetic acid, L-
Lactic acid, DL-lactic acid, D-lactic acid, viruvic acid, and alkali metal salts or alkaline earth metal salts of these carboxylic acids, or esters and acid amides, these compounds suppress the production of tyrosinase itself. Things
Compared to those that inhibit the action or activity of tyrosinase,
As a result, it can be said to be significant in that it exhibits a superior melanin production inhibitory action.

However, in the process of repeating the invention,
The present invention has been completed based on the finding that a specific butyric acid compound, which is not disclosed in the above invention, has a selective and excellent melanin production inhibitory action.

[Means for solving the problem]

That is, according to the present invention, 2-hydroxybutyric acid (CH
₃ CH ₂ (OH) CHCOOH), 3-hydroxybutyric acid (CH ₃ CH (OH) C
H ₂ COOH), 4-hydroxybutyric acid (OH (CH ₂ ) ₃ COOH) and their sodium salts (CH ₃ CH ₂ (OH) CHCOONa, CH ₃ CH (O
H) CH ₂ COONa, OH (CH ₂ ) ₃ COONa) An external preparation for suppressing melanin production is provided, which comprises one or more compounds selected from the group consisting of CH ₂ COONa and OH (CH ₂ ) ₃ COONa) as an active ingredient.

The external preparation of the present invention is prepared by blending one or more of the above-mentioned compounds with a usual cosmetic base or ointment base, and the like to prepare creams, emulsions, poultices, packs, lotions, ointments, etc. To be used as a dosage form.

The above-mentioned compound, which is the active ingredient of the present invention, is used in the range of 0.001 to 50% by weight, preferably 0.001 to 10% by weight, based on the total amount of the external preparation, and even when two or more kinds are used in combination, the total amount thereof is Is preferably in this range.

In the case of compounding, when the external preparation is a mixture of an oil phase part and an aqueous phase part, it is compounded in the aqueous phase part in advance, and when the alcohol phase and the aqueous phase are mixed, the alcohol phase or the water phase is mixed. It may be mixed in any of the phases.

That is, for example, in the case of cream or ointment,
As the water phase part, a predetermined amount of the butyric acid compound is added to purified water together with a moisturizing agent such as glycerin or sorbit, and as the oil phase part, solids such as beeswax, paraffin, microcristan wax, ceresin, higher fatty acid and hardened oil are mixed. Oils, semi-solid oils such as petrolatum, lanolin and glycerides, and liquid oils such as squalane, liquid paraffin and various ester oils to which oil components such as preservatives and surfactants are added are prepared. The aqueous phase obtained in this way is heated to a temperature of about 70 ° C and gently stirred, while the oil phase heated to a similar temperature is gradually added to emulsify the cream or ointment. And

In the case of lotion and lotion, together with a moisturizer such as glycerin and propylin glycol and a skin nutrient in purified water, a predetermined amount of the butyric acid compound is blended to form an aqueous phase part,
This is mixed with a preservative, a fragrance, etc. dissolved in alcohol at room temperature to prepare a lotion or lotion.

In the case of an emulsion, a predetermined amount of the butyric acid compound is added to a purified water with a patch such as glycerin and a pH adjusting agent consisting of an acid or an alkali, and ethanol is added to the mixture which is heated to about 70 ° C and the aqueous phase part is added. And On the other hand, solid oils such as beeswax and paraffin, semi-solid oils such as petrolatum and lanolin, liquid oils such as squalane, liquid paraffin and various ester oils are mixed with oily ingredients such as preservatives and surfactants and mixed and heated. The oil phase is used. Next, the oil phase part is added to the water phase part for preliminary emulsification, and a protective colloid agent such as carboxyvinyl polymer and carboxymethyl cellulose is added thereto, and the mixture is uniformly emulsified with a homomixer to obtain an emulsion.

In packs, moisturizers such as glycerin and polyvinyl alcohol, filming agents such as bee gum are added to purified water to swell, and if necessary, powder components such as kaolin, talc, and zinc oxide are added. Then, ethanol in which a predetermined amount of the butyric acid compound is dissolved is added together with a fragrance and a preservative, and the mixture is kneaded to form a paste to obtain a pack.

In poultices, a predetermined amount of the butyric acid compound is dissolved in warm water such as glycerin or propylene glycol, purified water, and gelatin, sodium carboxymethyl cellulose, methyl cellulose, water-soluble polymer such as sodium polyacrylate, A filler such as titanium oxide, an antiseptic, a surfactant, etc. are added and mixed to make a uniform poultice.

In the present invention, the butyric acid compound was evaluated for its melanin production inhibitory effect by the following method.

 The following were used as butyric acid compounds.

(1) 2-hydroxybutyric acid (2) 3-hydroxybutyric acid (3) 4-hydroxybutyric acid (4) sodium 2-hydroxybutyrate (5) sodium 3-hydroxybutyrate (6) sodium 4-hydroxybutyrate (7) α- Hydroxyisobutyric acid (control) (8) α-Hydroxyisovaleric acid (control) Evaluation of melanin production inhibitory effect In mouse melanoma-derived melanoma-containing MEM medium containing 10% fetal calf serum B-16 cultured cells were seeded and cultured at 37 ° C under 5% CO ₂ conditions for 5 days, then the cells were dispersed with trypsin and centrifuged at 1000 rpm for 5 minutes to collect the cells. It was judged by.

 The criteria for judgment are as follows.

-: Similar to that without addition of melanin production inhibitory substance +: Slightly whitening ++: Fairly whitening +++: Almost whitening The results are shown in the table.

[Examples] Ointment (% by weight) Polyoxyethylene sorbitan monostearate (60E.O) 1.00 Poroexie styrene molytooleate Sorbent (60E.O) 1.50 Glycerin monostearate 1.50 Salami beeswax 2.00 Paraffin 2.00 Stearic acid 3.00 Behenyl alcohol 3.00 Liquid paraffin 5.00 Preservative Suitable amount Perfume Trace amount 1,3-butylene glycol 5.00 Citric acid 0.30 2-Hydroxybutyric acid 1.00 Purified water to 100 cream (wt%) Polyoxyethylene oleyl ether (POEO) 1.60 Glycerin monostearate 3.00 Salami beeswax 2.80 Cetanol 3.00 Stearic acid 1.75 Liquid paraffin 7.10 Squalane 5.00 Glycerin 2.50 Carbopol 940 0.08 Clewat N 0.01 3-Hydroxybutyric acid 1.00 Purified water ~ 100 Emulsion (wt%) Polyoxyethylene monostearate Recall (40E.O) 2.00 Self-emulsifying glycerin monostearate 5.00 Stearic acid 5.00 Behenyl alcohol 1.00 Liquid paraffin 1.00 Glyceryl trioctanoate 10.00 Preservative A suitable amount Fragrance 1,3-butylene glycol 5.00 4-Hydroxybutyric acid 1.00 Purified water to 100 lotion (Wt%) Polyoxyethylene hydrogenated castor oil (60E.O) 1.00 Ethanol 15.00 Citric acid 0.10 Sodium citrate 0.30 1,3-Butylene glycol 4.00 Sodium 2-hydroxybutyrate 1.00 Preservative A suitable amount Fragrance Purified water to 100 Lotion ( Weight%) Citric acid 0.40 Calcium carbonate 0.20 Ethanol 6.00 Propylene glycol 9.00 9.00 Sodium 3-hydroxybutyrate 1.00 Preservative Suitable amount Fragrance Trace amount Purified water-100 packs (wt%) Veegum 5.00 Squalane 2.00 Propylene glycol 5.00 Zinc oxide 10.00 Ethano 5.00 Sodium 4-hydroxybutyrate 1.00 Preservative Suitable amount Perfume Trace amount Purified water -100 Pap (wt%) Polyacrylic acid 30.00 2-Hydroxybutyric acid 10.00 Sorbitan monooleate 1.00 Purified water -100 Sodium polyacrylate 7.00 Ammonium chloride 0.30 Concentrated Glycerin 20.00 Titanium oxide 1.00 [Effect of the invention] As described above, the present invention is a useful invention which provides a highly safe external preparation for melanin production inhibition which significantly suppresses melanin production.

Claims (1)

(57) [Claims] 1. 2-Hydroxybutyric acid, 3-hydroxybutyric acid, 4
An external preparation for suppressing melanin production, which comprises a compound selected from the group consisting of hydroxybutyric acid and sodium salts thereof as an active ingredient.