JP2974146B2 - Topical melanin production inhibitor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION TECHNICAL FIELD OF THE INVENTION

The present invention suppresses erythema and pigmentation of the skin due to ultraviolet rays, enhances the effect of preventing skin spots of melanin such as spots and freckles due to sunburn, and furthermore, kojic acid or kojic acid which prevents coloring of external preparations during use. The present invention relates to an external preparation containing a derivative as an active ingredient.

[Prior art]

Kojic acid and kojic acid derivatives are known as substances that suppress the production of melanin generated in human skin. And
Skin coatings containing these substances as active ingredients are also known. For example, a whitening cosmetic containing kojic acid as a whitening component (JP-A-53-3538, JP-B-56-18569), an aliphatic carboxylic acid diester of kojic acid, and an aliphatic carboxylic acid monoester of kojic acid may be used. Fair-skin cosmetics as whitening ingredients (JP-A-61-60801, JP-B-60-9722),
Fair-skin cosmetics containing an ester of an aromatic carboxylic acid such as cinnamic acid or benzoic acid as a whitening component (Japanese Patent Publication No. 60-10005)
Japanese Patent Application Laid-open No. 61-10447) and an ointment for suppressing melanin production containing kojic acid as an active ingredient. Further, in order to prevent kojic acid from changing with time and causing coloration, a cosmetic in which a 2-hydroxybenzophenone compound is blended with kojic acid is known (Japanese Patent Laid-Open No. 62-10 / 1987).
No. 8804).

[Problems to be solved by the invention]

As described above, kojic acid and kojic acid derivatives are extremely excellent substances that suppress the production of melanin. When this substance is used as a main ingredient in cosmetics and external preparations for the skin, when applied to the skin, it has excellent skin-whitening and melanin production-inhibiting effects, and does not cause any damage to the skin. It is known as a coating agent and is usefully used. However, even if pigmentation such as liver spots is improved by the action of kojic acid, the pigmentation that has been healed may return to its original state due to the effect of ultraviolet rays when exposed to direct sunlight. It is also pointed out that when these external preparations are applied to the skin and exposed to strong direct sunlight outdoors, the external preparations may be colored. Therefore, an object of the present invention is to remove various adverse effects of kojic acid and kojic acid derivatives, and also prevent coloring during use,
In addition, it is an object of the present invention to provide an external preparation containing kojic acid or a kojic acid derivative as an active ingredient which does not cause any damage to human skin even when the external preparation is used.

[Means for Solving the Problems]

The present inventor has found that an external preparation containing kojic acid and a kojic acid derivative suppresses erythema and pigmentation due to ultraviolet rays, enhances the effect of preventing spots and freckles caused by sunburn, prevents coloring during use, and furthermore, uses the external preparation. As a result of repeated studies for the purpose of obtaining an external preparation containing kojic acid, a kojic acid derivative as an active ingredient, which does not cause any damage to human skin even when using it,
An external preparation comprising a kojic acid or a kojic acid derivative as an active ingredient and a specific ultraviolet absorbing substance mixed with the external preparation, when applied to the skin, there is no erythema or pigmentation on the skin after application even when irradiated with ultraviolet rays The inventors have found that the phenomenon and coloring during use are also prevented, and the present invention has been completed. That is, according to the present invention, in the external preparation containing kojic acid or a kojic acid derivative, ethylene glycol salicylate, octyl salicylate, dipropylene glycol salicylate, myristyl salicylate, salicylate acetamidophenyl, diphenhydramine salicylate, methyl salicylate, homomenthyl salicylate, triethanol salicylate. An external preparation for suppressing melanin production, characterized by comprising an ultraviolet absorbing substance comprising a salicylic acid-based compound and / or a methoxycinnamic acid-based compound selected from the group consisting of amines. Further, according to the present invention, there is provided an external preparation for suppressing melanin production, which further comprises a benzophenone-based compound added to the above external preparation.

BEST MODE FOR CARRYING OUT THE INVENTION

Kojic acid as an active ingredient of the external preparation of the present invention is 5-oxy-2 produced from various carbohydrates by a kojic acid-producing strain belonging to the genus Aspergillus, Penicillium and the like.
-Oxymethyl-γ-pyrone. Examples of the kojic acid derivative include kojic acid monofatty acid esters such as kojic acid monopalmitate, kojic acid monobutyrate, kojic acid monocaprylate, kojic acid monostearate (see Japanese Patent Publication No. 58-22152), and kojic acid diacid. Fatty acid esters such as kojic acid dipalmitate, kojic acid dibutyrate, kojic acid dioleate, kojic acid distearate, kojic acid monocinnamoate,
And kojic acid monobenzoate (see Japanese Patent Publication No. 60-10005). If the external preparation of the present invention is used for the purpose of suppressing melanin production and preventing melanin deposition on the skin, in addition to cosmetics such as creams, lotions, packs, and powders, emulsions and lotions Preparations, liniments, ointments and the like can be formulated into various externally used forms such as quasi-drugs. , A stabilizer, a pigment, a fragrance, an antioxidant, a preservative, a sequestering agent, and the like are appropriately blended and formulated into an external preparation by an ordinary method. The salicylic acid-based compound of the ultraviolet absorbing substance used to prevent the coloring of the external preparation containing the kojic acid and the kojic acid derivative of the present invention is ethylene glycol salicylate, octyl salicylate, dipropylene glycol salicylate,
It is selected from the group consisting of myristyl salicylate, acetamidophenyl salicylate, diphenhydramine salicylate, methyl salicylate, homomenthyl salicylate, and triethanolamine salicylate, with octyl salicylate being preferred. Examples of the methoxycinnamic acid compounds include sinoxate, methyl diisopropylcinnamate, isopropyl paramethoxycinnamate, ethyl paramethoxycinnamate, potassium paramethoxycinnamate, sodium paramethoxycinnamate, octyl methoxycinnamate, and diethanolamine 4-methoxycinnamate. Preferred is octyl methoxycinnamate. Benzophenone-based compounds include oxybenzone, oxybenzonesulfonic acid, dihydroxydimethoxybenzophenone, sodium dihydroxybenzophenonesulfonate, dihydroxybenzophenone, tetrahydroxybenzophenone, sodium hydroxymethoxybenzophenonesulfonate, p-hydroxybenzophenone, p-hydroxybenzophenone,
-Methoxybenzophenone, dioxybenzophenone,
4-phenylbenzophenone-2'-carboxylate 2-ethylhexyl, benzophenone derivative polyvalent metal salts, benzophenone derivatives using benzophenones as phenolate salts, and the like. Preferred is tetrahydroxybenzophenone. In the present invention, by adding 0.001 to 5.0% (by weight) of each of the above-mentioned ultraviolet absorbing substances alone or two or more with respect to the total amount of the external preparation, erythema and pigment of skin due to ultraviolet rays of kojic acid and kojic acid derivative can be sufficiently obtained. It suppresses deposition, enhances the effect of preventing spots and freckles due to sunburn, and can prevent coloring of external preparations during use. The external preparation of the present invention may further comprise 2-
(2-hydroxy-5-methylphenyl) -benzotriazole, 2- (2'-hydroxy-5-t-octylphenyl) -benzotriazole, oxybenzotriazole, urocanic acid, ethyl urocanate, methyl anthranilate, anthranilate Menthyl, 3- (4-methylbenzylidene) camphor, 3- (4-trimethylaminobenzylidene) camphor methosulfate, 2-phenylbenzimidazole-5-sulfonic acid, sodium 3,4-dimethylphenylglyoxalate, 5- (3,3
-Dimethyl-2-norbornylidene) -3-pentene-
2-one, dicaroyl trioleate, Lawson and 3%
Mixture with dihydroxyacetone, 2-cyano-3,3 '
-2-ethylhexyl diphenylacrylate, red
Petrotam, N- (hydroxystil) benzamide,
2-phenacylthiazoline derivative, α-dehydroamino acid derivative, furan derivative, chalcone derivative, 5- (3,4
(Dimethoxy) benzyl-3-hydantoin UV-absorbing substances of plant components such as octyl propionate, aloe extract, pentagon extractant, shea butter, γ-oryzanol, soybean oil, etc. The effect can also be enhanced. In addition, anionic substances such as sodium N-lauroyl-L-glutamate and sodium dl-pyrrolidonecarboxylate, stearyltrimentylammonium chloride,
Cationic substances such as cetyltrimethylammonium chloride, nicotinamide, nicotinic acid, natural vitamin E,
An antioxidant such as sodium bisulfite and a pH adjuster such as monosodium L-glutamate, potassium sodium tartrate, sodium alginate and monosodium L-aspartate can also be added. Next, examples of the present invention and test examples on suppression of erythema and pigmentation of skin by ultraviolet rays and prevention of coloring of external preparations will be described.

【Example】

Example 1 (Emulsion) Polyoxyethylene sorbitan monostearate (20
EO) 1.00g, polyoxyethylene sorbite tetraoleate (60E.O.) 0.50g, lipophilic glyceryl monostearate 0.50g, stearic acid 0.50g, behenyl alcohol 0.50g, avocado oil 4.00g, glyceryl trioctanoate
4.00 g, 0.20 g of ethyl parahydroxybenzoate and 1.00 g of octyl salicylate are heated and dissolved. Separately, 5.00 g of 1,3-butylene glycol, 0.14 g of xanthan gum and 73.1 of purified water
Heat and mix 5 g. The latter solution is added to the former solution, emulsified, stirred, and cooled. This is disodium edetate
Add 0.01 g, 1.00 g of kojic acid and 8.00 g of purified water, stir,
After mixing, the mixture is cooled to obtain an emulsion. Example 2 (cream) Polyethylene glycol monostearate (40E.O.)
2.00 g, self-emulsifying glyceryl monostearate 5.00 g,
Heat and dissolve 5.00 g of stearic acid, 1.00 g of behenyl alcohol, 10.00 g of liquid paraffin, 10.00 g of glyceryl trioctanoate, 0.20 g of ethyl parahydroxybenzoate and 2.00 g of octyl methoxycinnamate. Separately, 5.00 g of 1,3-butylene glycol and 50.79 g of purified water are added, and heated and mixed. The latter solution is added to the former solution, emulsified, stirred, and cooled. To this, 0.01 g of disodium edetate, 1.00 g of kojic acid and 8.00 g of purified water are added, mixed with stirring, and cooled to obtain a cream. Test example Test sample a) Polyethylene glycol monostearate (40E.
O.) 2.00 g, self-emulsifying glyceryl monostearate 5.0
0 g, stearic acid 5.00 g, behenyl alcohol 1.00 g, liquid paraffin 10.00 g, glyceryl trioctanoate 10.00 g
And 0.20 g of ethyl parahydroxybenzoate are heated and dissolved. Separately, 5.00 g of 1,3-butylene glycol and 5 parts of purified water
Add 9.79g, warm and mix. The latter solution is added to the former solution, emulsified, stirred, and cooled. To this, 0.01 g of disodium edetate and 2.00 g of purified water were added, and the mixture was stirred and mixed to obtain a cream (control). b) Cream containing 1 g of kojic acid added to test sample a) (control). c) Cream containing 1.0 g of octyl salicylate added to test sample b) (external preparation of the present invention). d) Cream containing 2.0 g of octyl methoxycinnamate added to test sample b) (external preparation of the present invention). Test Example 1 Cream Coloring Test The test samples a), b), c) and d) were placed in a plastic petri dish and irradiated with ultraviolet rays [FL20S / BLB lamp (manufactured by Tokyo Shibaura Electric Co., Ltd.)] (25J / cm ² ). Immediately after the irradiation, the degree of coloring of the cream of each sample was observed with the naked eye, and a pigment meter [Z-1001DP manufactured by Nippon Denshoku Industries Co., Ltd.]
And the color difference (ΔE) before and after the ultraviolet irradiation. The results are shown in Table 1. Evaluation criteria of visual coloring degree ++: Coloring is remarkably recognized. +: Coloring is recognized for lightness. ±: Slight coloring is observed. -: Coloring is not recognized. As described above, it is apparent that coloring is significantly prevented in the samples c) and d) of the product of the present invention. Test Example 2 Erythema and Pigmentation Inhibition Test Seven (2 × 2 cm) sites were provided on the upper back of the subjects (46 healthy male volunteers). An aluminum foil was set on the upper back so that only the test site could be irradiated with ultraviolet light, and two FL20S / BLB lamps and two FL20S / E-30 lamps (from Tokyo Shibaura Electric Co., Ltd.) at a distance of 10 cm were each 0.8 × 10 at the same time. Irradiation was performed at ^-7 erg / cm ² / time / day three times a day. Before irradiation, the damage test section was thoroughly washed with warm water. Each test sample a), b), c), d) was applied to each site three times a day (morning, noon, night), and erythema was observed by visual observation 3 days after the test start date, 7 days and After 21 days, the degree of pigmentation was compared with the control a) and evaluated on a 4-point scale. The results are shown in Tables 2 to 4 below. 1) Erythema (3 days later) Sample b) (control) suppressed erythema as compared to sample a) (control) [71.8 was clearly thinner (++) or more]
%] Is the external preparation of the present invention, sample c) [obviously thin (++) or more: 78.3%], sample d) [obviously thin (+
+) Is more than 76.0%] suppressed erythema more than the control. 2) Pigmentation In both 7 days and 21 days, sample b) suppressed the induction of pigmentation more than sample a) [69.6 was clearly higher than (++).
%, 60.9%], the sample c) [80.4%, 82.6% for samples that are clearly thin (++) or more], sample d) [the sample is clearly thin (++)
78.3%, 82.6%] suppressed pigmentation more than the control. Evaluation criteria for visual coloring degree in the above test +++: markedly weak ++: markedly thin +: slightly thin-: no difference Test Example 3 Sun exposure test 5 × 5 cm below the shoulder blades of 10 healthy males Seven sites were provided. About 25 mg of each of the sample a), the sample b), the sample c), and the sample d) of Test Example 1 were applied to this site. The upper back, including each test site, was exposed to direct sunlight for 5 hours. The color change of each test sample was observed over time. The conditions at this time were as follows: Fukuoka Prefecture Weather Fine weather Temperature 25.0 to 29.0 ° C UV intensity 365 nm 4.25 to 4.95 mW / cm ² 305 nm 0.26 to 0.41 mW / cm ² Exposure time 10:30 to 15:30. Table 5 shows the results of this test. As is clear from the above results, changes in the color tone were observed in the applied external preparations in Samples a) and b), but no change was observed in Samples c) and d), which are the external preparations of the present invention. I couldn't.

【The invention's effect】

ADVANTAGE OF THE INVENTION According to this invention, the erythema and pigmentation of the skin by ultraviolet rays are suppressed by mix | blending a specific ultraviolet-absorbing substance with the external preparation containing kojic acid or a kojic acid derivative, and the skin of melanin, such as spots and freckles by sunburn, is obtained. There is provided an external preparation for suppressing melanin production, which has an enhanced effect of preventing deposition and which prevents coloring of the external preparation during use.

Claims (2)

(57) [Claims] 1. An external preparation containing kojic acid or a kojic acid derivative comprises ethylene glycol salicylate, octyl salicylate, dipropylene glycol salicylate, myristyl salicylate, acetamidophenyl salicylate, diphenhydramine salicylate, methyl salicylate, homomenthyl salicylate, triethanolamine salicylate. An external preparation for suppressing melanin production, comprising an ultraviolet absorbing substance comprising a salicylic acid compound and / or a methoxycinnamic acid compound selected from the group consisting of: 2. The external preparation for suppressing melanin production according to claim 1, further comprising a benzophenone compound.