JPH1121226A - Skin preparation for external use for suppressing melanin production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject skin preparation for external use having both of stability and safety, substantially useful and excellent in prevention of pigmentation and improving effect by including a specific coumarin derivative. SOLUTION: This skin preparation for external use is obtained by including, as an essential component, 0.00001-10 wt.%, preferably 0.001-5 wt.% coumarin derivative obtained by synthesis or by extraction and isolation of Aesculus hippocastanum L. and represented by the formula (R is H or OH) into a skin preparation for external use and further, properly formulating various arbitrary ingredients such as an oil solution, an aqueous ingredient, a surfactant, alcohols, a humectant, a thickener, preservatives, a pigment, powder, a pH adjuster, an ingredient having pharmacodynamic effects, an ultraviolet absorber, an antioxidant, a chelating agent, an antiinflammatory agent, a beautifying and whitening agent and a perfume, used for conventional cosmetics, quasi-drugs, medicines, etc., therewith.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a melanin production-suppressing external skin preparation containing a coumarin derivative.

[0002]

2. Description of the Related Art It is considered that skin spots, freckles and pigmentation after sunburn are caused by abnormal deposition of melanin pigments produced by the activation of pigment cells existing in the skin. Conventionally, in order to prevent and improve such skin spots and freckles, it is necessary to inhibit the activity of tyrosinase, which contributes to the production of melanin, to inhibit the melanin production process, or to quickly release melanin already produced. L-ascorbic acid and its derivatives, hydrogen peroxide, hydroquinone, arbutin, kojic acid, cysteine, glutathione, and the like have been used as whitening components in order to discharge or bleach light.

[0003]

However, these conventional whitening ingredients have extremely poor stability in the formulation and cause coloration and off-odor due to decomposition, and hydroquinone itself causes irreversible vitiligo. There are safety issues. Therefore, at present, there is no known component which has both stability and safety and is substantially useful in preventing and improving pigmentation.

[0004] An object of the present invention is to provide a melanin production-suppressing skin external preparation which has both stability and safety, and is substantially useful in preventing and improving pigmentation.

[0005]

Accordingly, the present invention has been intensively studied to obtain a skin preparation for external use having a useful effect of preventing and improving pigmentation. As a result, a specific coumarin derivative has excellent tyrosinase activity inhibitory activity and melanin production. It has been found that the compound has a strong inhibitory effect on the present invention, and has led to the present invention.

That is, the present invention provides a compound represented by the general formula (1)

[0007]

Embedded image

(Wherein, R represents H or OH)
The present invention relates to a melanin production-suppressing skin external preparation characterized by containing a coumarin derivative represented by the formula:

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The coumarin derivative represented by the general formula (1) used as a whitening component in the present invention may be synthesized by a known method, or by extracting and isolating horse chestnut by a known means. May be obtained by

[0010] The melanin production-suppressing skin external preparation of the present invention contains 0.00001-
10% by weight, preferably 0.001 to 5% by weight. Furthermore, the melanin production-suppressed skin external preparation of the present invention includes:
In addition to the essential components, ordinary cosmetics, quasi-drugs, various optional components used in pharmaceuticals and the like, for example, oils, aqueous components,
Surfactants, alcohols, humectants, thickeners, preservatives,
Pigments, powders, pH adjusters, medicinal ingredients, ultraviolet absorbers, antioxidants, chelating agents, anti-inflammatory agents, whitening agents, fragrances, and the like can be appropriately compounded.

Specifically, examples of oils include liquid paraffin, vaseline, paraffin wax, squalane, beeswax, carnauba wax, olive oil, lanolin, higher alcohols, fatty acids, synthetic ester oils of higher alcohols and fatty acids, silicone oils, and the like. Examples of the humectant include sorbitol, xylitol, glycerin, maltitol, propylene glycol, sodium pyrrolidonecarboxylate, polyethylene glycol, 1,3-butylene glycol, lactic acid, and sodium lactate.As the thickener, carboxyvinyl polymer, Carboxymethyl cellulose, polyvinyl alcohol, carrageenan,
Examples include water-soluble polymers such as gelatin, electrolytes such as sodium chloride and potassium chloride, and preservatives include methylparaben, ethylparaben, propylparaben, butylparaben, and sodium benzoate. Nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, and polyoxyethylene sorbitol fatty acid ester Talc, sericite, mica, kaolin, silica,
Bentonite, vermiculite, zinc white, mica, mica titanium, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, red iron oxide, ultramarine blue, etc., and pH adjusting agents such as citric acid-sodium citrate buffers Is mentioned. The medicinal ingredients include allantoin, vitamin E derivatives, glycyrrhizin, ascorbic acid derivatives, dipotassium glycyrrhizinate, kojic acid, arbutin, pantethic acid buckwheat, placenta extract, anti-inflammatory agents, yoquinin and other extractables, and these By adding C, the melanin suppressing effect can be improved. Furthermore, the sunburn prevention effect can be improved by blending various ultraviolet absorbers.

The melanin production-suppressing skin external preparation of the present invention can be produced by a conventional method. The melanin production-suppressed skin external preparation targeted by the present invention is useful as a whitening cosmetic, but is not limited to a whitening cosmetic.
It includes quasi-drugs, topical drugs, etc., and its dosage form is also ointment, cream, emulsion, lotion, foundation,
Packs, bath preparations, lotions, gels, solutions, sticks and the like can be arbitrarily selected depending on the purpose.

[0013]

EXAMPLES The present invention will now be described specifically with reference to examples, but the present invention is not limited to the examples.

The evaluation of the whitening effect and the tyrosinase activity inhibitory effect in this example was carried out by the following whitening effect test for UV-B-induced pigment spots and B16 menorama cell culture test.

Example 1 The upper arms of the 40 test subjects were irradiated with ultraviolet rays in the UV-B region twice the minimum erythema dose once a day for 2 days once a day for 40 days. The whitening effect by continuously applying the samples shown in Table 2 to the test site for three months was examined.
Evaluation was made using a colorimeter (SE-2000 manufactured by Nippon Denshoku Industries)
The L * value was calculated from the spectral reflectance, and the ΔL * value representing the recovery was used. Note that ΔL * was defined as follows. ＬL * is represented by the following formula, where L * value before application at the site to which the sample is applied is L * 0 and L * value at each site after continuous application З months is L * 90, and the result of ΔL * Were classified and evaluated as shown in Table 1.

The amount of change ΔL * = L * 90−L * 0 (Equation 1)

[0017]

[Table 1]

[0018]

[Table 2]

As is evident from the results shown in Table 2, the practice of the present invention containing the coumarin derivative in comparison with the creams of Comparative Example 1 containing no whitening component and Comparative Examples 2 and 3 containing the known whitening component was carried out. It can be seen that the cream of Example 1 has an excellent whitening effect.

Example 2 (B16 Menorama Cell Culture Test) Samples of various concentrations were added to a B16 menorama cell culture plate, and the effect on melanin was examined. After completion of the culture test, the medium was removed, washed with phosphate buffered saline (PBS), the cells were detached from the flask using a medium containing trypsin and EDTA, and the cells were recovered from the cell suspension by centrifugation. . After the obtained cells were washed once with PBS, a fixed amount of PBS was added, the cells were mixed by flushing, a certain amount of the cell suspension was taken, and the number of cells was measured with a Coulter counter. In addition, the remaining turbid solution was centrifuged, the color tone was measured with the naked eye, and the results were expressed in terms of (%) when the number of cells in the case of using 1 to 3 (control) was set to 100.

Evaluation point 3: Clear whitening compared to solvent control (Control) Evaluation point 2: Slight whitening compared to solvent control (Control) Evaluation point 1: Equivalent to solvent control (Control)

[0022]

[Table 3]

Thereafter, 1N sodium hydroxide was further added and dissolved by heating. After cooling, chloroform was added and the mixture was centrifuged again. The absorbance at 400 nm of the obtained supernatant was measured, and the amount of lime melanin was determined from a calibration curve prepared in advance using synthetic melanin. The suppression rates in the table are as shown in the following equation.

[0024]

(Equation 1)

[0025]

[Table 4]

Thus, the coumarin derivative extracted and isolated from horse chestnut has the action of suppressing the production of melanin and eliminating the melanin pigmentation formed by the stimulation of ultraviolet rays and the like. Is
It has an excellent whitening effect, an effect of preventing and improving spots and freckles due to sunburn, and is highly safe.

Example 3 Cream (Component) (W / W%) (1) Glycerin monostearate 5.0 (2) Polyethylene glycol monostearate (25EO) 2.0 (3) Squalane 5 (4) Jojoba oil 3.0 (5) Cetanol 5.0 (6) Glyceryl trioctanoate 8.0 (7) Glycerin 4.0 (8) 1,3-butylene glycol 5.0 (9) Coumarin derivative (General formula (1): R = OH) 0.5 (11) Remaining amount of purified water (12) Preservative appropriate amount (13) Flavor appropriate amount

Example 4 Cream (ingredient) (W / W%) (1) Decaglyceryl monomyristate 2.0 (2) Stearic acid 4.0 (3) Cetanol 2.0 (4) Hydrogenated soybean phospholipid 1.0 (5) Glyceryl trioctanoate 6.0 (6) Squalane 6.0 (7) Cetyl palmitate 2.0 (8) Methylpolysiloxane (50cs) 0.5 (9) Coumarin derivative (general formula (1) ): R = OH) 0.5 (10) Xanthan gum 7.0 (11) Sodium hyaluronate 0.5 (12) Remaining purified water (13) Preservative appropriate amount (14) Flavor appropriate amount

Example 5 Emulsion (Component) (W / W%) (1) Glyceryl oleate 1.0 (2) Polyoxyethylene sorbitan tristearate (20EO) 1.0 (3) Monostearic acid Glyceryl 1.0 (4) Squalane 5.0 (5) Behenyl alcohol 5.0 (6) Glyceryl trioctanoate 2.0 (7) Octyldodecyl myristate 2.0 (8) Octyl methoxycinnamate 2.0 (9 ) 1,3-butylene glycol 5.0 (10) Coumarin derivative (general formula (1): R = OH) 0.5 (11) Dipotassium glycyrrhizinate 0.5 (12) Glycerin 2.0 (13) Purified water Remaining amount (14) Preservative appropriate amount (15) Fragrance appropriate amount

Example 6 Emulsion (Component) (W / W%) (1) Stearic acid 2.0 (2) Cetanol 1.5 (3) Vaseline 4.0 (4) Squalane 5.0 (5) Trioctanoic acid Glyceryl 2.0 (6) Dipropylene glycol 2.0 (7) 1,3-butylene glycol 3.0 (8) Coumarin derivative (general formula (1): R = OH) 0.5 (9) Purified water residue Amount (10) Preservative appropriate amount (11) Fragrance appropriate amount

Example 7 Lotion (Component) (W / W%) (1) 1,3-butylene glycol 3.0 (2) Glycerin 2.0 (3) Sodium hyaluronate 0.5 (4) Ethanol 2 0.0 (5) citric acid 0.5 (6) sodium citrate 0.5 (7) disodium edetate 0.5 (8) pyroglutamic acid isostearate polyoxyethylene glyceryl (25EO) 0.04 ( 9) Coumarin derivative (general formula (1): R = OH) 0.5 (10) Preservative appropriate amount (11) Purified water remaining amount (12) Perfume appropriate amount Also in Examples 3 to 7, the effect of suppressing melanin production was confirmed. confirmed.

[0032]

The coumarin derivative of the general formula (1) extracted and isolated from horse chestnut has a tyrosinase activity inhibitory action, suppresses melanin production, and has an action of preventing and improving pigmentation caused by melanin produced. An external preparation for skin containing the same has an excellent whitening effect, an effect of preventing and improving spots and freckles due to sunburn, and is highly safe.

Claims (1)

[Claims] 1. A compound of the general formula (1) (Wherein, R represents H or OH) A melanin production-suppressing skin external preparation comprising a coumarin derivative represented by the formula: