JPH06321758A - Skin beautifying agent - Google Patents

Abstract

PURPOSE:To obtain a skin beautifying agent having actions to suppress melanogenesis and dissipate pigmentation formed by the stimulation with ultraviolet rays, etc., and giving a skin cosmetic having excellent skin beautifying effect and the preventing and treating effect on the spots and freckles caused by sunburn, etc. CONSTITUTION:A skin beautifying agent composed of a compound of the formula (R<1> and R<2> are OH, lower alkoxy or sulfate residue) and a skin cosmetic containing the compound. The compound of the formula can be separated from the extraction liquid of the twig of southern bayberry (Myrica cerifera). The amount of compound of the formula to be compounded to the skin cosmetic is preferably 0.00001-10wt.%, especially 0.0001-5wt.%. This skin cosmetic includes quasi-drugs and medicines for external use, etc., as well as common skin cosmetics. It is used in various forms such as cream, milky lotion, face lotion, foundation, pack, lotion, gel, solution or stick according to the use.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a whitening agent and a skin cosmetic, and more particularly to a skin cosmetic having an excellent whitening effect on the skin after ultraviolet irradiation and capable of preventing and treating spots and freckles caused by sunburn. Regarding fees.

[0002]

2. Description of the Related Art Pigments, freckles, and pigmentation on the skin after sunburn are less likely to occur, increase, or disappear with age, which is a problem for middle-aged and older people. Although the pathogenic mechanism of these pigmentation diseases has not been clarified yet,
It is considered that the mechanism of melanin synthesis in epidermal melanocytes was enhanced by the action of sunlight, especially ultraviolet rays, and melanocyte-stimulating hormone. Moreover, it is considered that the delay in keratinization of epidermal keratinocytes (keratinocytes) with aging also causes an increase in the density of melanin granules in the epidermis, that is, a clinically symptomatic increase in pigmentation. These pigmented areas are localized and may be distinctly different from the surrounding normal skin color.

There is a strong demand for the development of a drug capable of recovering such an acquired pigment (ie, melanin) deposit to a normal skin color, and many drugs have been commercialized so far. For example, in recent years, vitamin C has an excellent reducing ability.
Cosmetics containing a (L-ascorbic acid) derivative have also been used. However, this also has a difficulty in stability, and almost no effect is observed for external use. On the other hand, in Europe and America, it is known that hydroquinone has a therapeutic effect on spots and an effect to whiten black skin, but these also have problems in safety of the substance itself (irritation, allergenicity), and Compounding as a drug is problematic in that it may cause vitiligo in some cases. In addition, various components such as isoflavone derivatives (Japanese Patent Laid-Open No. 58-58
225004) and p-hydroxycinnamic acid derivatives as cinnamic acid derivatives (JP-A-59-196813) are known as melanin inhibitors.

[0004]

However, at present, no substance is known that has a sufficient pigmentation preventing / ameliorating effect and compoundability with a cosmetic base. Therefore, an object of the present invention is to provide a component having an excellent whitening effect and useful as a cosmetic, and a skin cosmetic containing the same.

[0005]

[Means for Solving the Problems] Therefore, the inventors of the present invention, through research on the mechanism of melanin production, have made earnest efforts to obtain a substance that suppresses melanin production in melanocytes and reduces or eliminates pigmentation due to external stimuli such as ultraviolet rays. As a result of investigation, it was found that the compound represented by the following general formula (1) has an excellent melanin suppressing effect and an effect of preventing / improving pigmentation, and by adding this, a good skin cosmetic composition can be obtained. The invention was completed.

That is, the present invention has the following general formula (1):

[0007]

[Chemical 2]

A whitening agent comprising a compound represented by the formula: wherein R ¹ and R ² each represent a hydroxyl group, a lower alkoxy group or a sulfur residue, or a salt thereof.

The present invention also provides a skin cosmetic containing the compound (1) or a salt thereof.

The compound (1), which is an active ingredient of the skin cosmetic composition of the present invention, or a salt thereof has already been converted to Souco bayberry (Sou).
then bayberry, Myrica cer
It has been reported to be isolated from the extract of the branch of ifera) and exhibit a hypotensive effect [Fujimoto,
M. , Mihara, S .; , Nakajima, S .; ，
Ueda, M .; , Nakamura, M .; , Sakura
ai, K .; , FEBS Letters (1992) 3
05, 41], but the effect of the compound on the skin is not known at all. In the general formula (1), R ¹ and R
Examples of the lower alkoxy group represented by ² include alkyl groups having 1 to 5 carbon atoms such as methoxy group, ethoxy group and propoxy group. Examples of the salt of compound (1) include sodium salt and potassium salt, and these salts can be produced according to a conventional method.

The compound (1) is contained in the skin cosmetic of the present invention in an amount of 0.00001 to 10% by weight (hereinafter simply referred to as%),
It is particularly preferable to add 0.0001 to 5%.

In addition to the above essential ingredients, the skin cosmetic of the present invention also contains various optional ingredients used in ordinary cosmetics, quasi drugs, pharmaceuticals, etc., such as oils, moisturizers, thickeners and antiseptics. Agents, emulsifiers, pigments, powders, pH adjusters, medicinal components, ultraviolet absorbers, antioxidants, fragrances and the like can be appropriately added.

Specific examples of the oil agent include liquid paraffin, petrolatum, 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 moisturizers include sorbitol, xylitol, glycerin, maltitol, propylene glycol, sodium pyrrolidonecarboxylate, polyoxypropylene fatty acid ester, polyethylene glycol, and the like, and thickeners include carboxyvinyl polymer, carboxymethylcellulose, polyvinyl alcohol, carrageenan. , Water-soluble polymers such as gelatin, and electrolytes such as sodium chloride and potassium chloride. Preservatives include methylparaben, ethylparaben, propylpa Ben, butyl paraben, sodium benzoate and the like can be mentioned. As the emulsifier, polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester. , Nonionic surfactants such as polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitol fatty acid ester, etc., powders such as talc, sericite, mica, kaolin, silica, bentonite, vermiculite, zinc white, mica, mica. Examples include titanium, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, red iron oxide, iron oxide, ultramarine blue, and the like, and examples of pH adjusters include buffering agents such as citric acid-sodium citrate. Examples of the medicinal component include arbutin, kojic acid, vitamin C and its derivatives, placenta extract, dipotassium glycyrrhizinate, allantoin, vitamin E derivative, pantethenic acid derivative, yoquinin, and various plant extracts.

The skin cosmetic of the present invention can be manufactured by a conventional method. Further, the skin cosmetics to be the subject of the present invention are not limited to general skin cosmetics, but include quasi drugs, external medicines, and the like, and their dosage forms are creams, emulsions, and lotions. , Foundation, pack,
A lotion form, a gel form, a solution form, a stick form, etc. can be arbitrarily selected according to the purpose.

[0015]

ACTION AND EFFECTS OF THE INVENTION The compound (1) has an excellent melanin pigmentation preventing / ameliorating effect by suppressing the melanin production of melanocytes, and the cosmetic containing this compound has an excellent whitening effect and sunburn. It has a preventive and therapeutic effect on spots and freckles due to the above, and is highly safe.

[0016]

EXAMPLES The present invention will be described in more detail below with reference to examples, but the present invention is not limited thereto.

Example 1 (Effect of Cultured Human Melanocytes on Melanin Production) Samples of various concentrations were added to a culture plate of normal human melanocytes to examine the effect on cell melanin production. (Test method) Normal human melanocytes (trade name: melanopack) marketed by Kurabo Industries were subcultured according to a conventional method and subjected to the present test. The test was added to this cell culture plate so that the final concentration was 0.00001 to 100 μM, and the effect of melanocytes on melanin production after a certain period was examined. The effect on melanin production was performed by quantifying the amount of radioactive thiouracil incorporated into cells, collecting the cells, visually observing the color tone of the cell pellet, and assigning evaluation points of 1 to 4. The color tone was judged according to the judgment criteria shown in Table 1. The evaluation was shown by the average of the evaluation points of 10 culture plates.

[0018]

[Table 1]

(Results) As shown in FIG. 1, the incorporation of radioactive thiouracil into the cells was 0.001 μM or more and the test sample (compound (1a): R ¹ = 3-O in the general formula (1)).
(H, R ² = 4-OH) was found to significantly inhibit the incorporation thereof as compared to untreated. Further, as shown in Table 2, the color of the cell pellet was visually determined to be 0.1 μM.
A clear whitening of the cells was observed at the concentration of. From the above results, compound (1) was confirmed to have an inhibitory effect on the melanin production of cultured human melanin-producing cells.

[0020]

[Table 2]

Example 1 (Extinction effect on UVB pigment spots) After carefully shaving the back hair of 20 brown guinea pigs with a hair clipper and a shaver, UV rays in the UVB region were applied twice as much as the minimum erythema dose (MED). Irradiation was carried out once a day for 3 days, and the amount of pigment spot elimination was examined by continuously applying the sample to the test site twice a day for one month to the induced pigment spots. As the sample, the compound 1a, the compound 1b, or the compound 1 is used.
An 80% ethanol solution containing 0.5% of c was used, and only 80% ethanol was used as a control. For the evaluation, the L ^* value was calculated from the Munsell value obtained by measuring with a color difference meter, and the ΔL ^* (change over time) of the sample-applied site was used to determine the ΔL ^{* of the} sample-uncoated (solvent only = control) site ^.
The value (ΔΔL ^* ) obtained by subtracting (aging change) was used. Note that ΔΔL ^* is expressed by the following formula. ΔΔL ^* = (L ^* _1- L ^* ₀ )-(L ' ^* _1- L' ^* ₀ ) L ^* ₀ ; sample-applied test site before application L ' ^* ₀ ; sample-unapplied test site before application L ^* ₁ ; Sample-applied test site after 1 month of continuous application L ' ^* ₁ ; Sample-unapplied test site after 1 month of continuous application The evaluation was shown by the average value of the evaluation points (Table 3) of 20 test animals.

[0022]

[Table 3]

As a result, as shown in Table 4, compound (1)
In the composition containing the above, a clearing effect of the pigment spot was recognized as compared with the control.

[0024]

[Table 4]

[0025]

Table 5 Example 2 (Cream) (Composition) (%) (1) Glycerin monostearate 5.0 (2) Polyethylene glycol monostearate 2.0 (3) Squalane 8.0 (4) Stearyl alcohol 5 0.0 (5) Glyceryl trioctanoate 8.0 (6) Dimethylpolysiloxane (50cs) 0.5 (7) Glycerin 5.0 (8) Citric acid 0.5 (9) Sodium citrate 0.5 (10) Compound 1a 0.1 (11) 6-amino-n-caproic acid 0.5 (12) Purified water Remaining amount (13) Preservative proper amount (14) Perfume proper amount

[0026]

Table 6 Example 3 (essence) (composition) (%) (1) 1,3-butylene glycol 8.0 (2) glycerin 4.0 (3) xanthan gum 0.3 (4) sodium chondroitin sulfate 0. 1 (5) Sodium hyaluronate 0.1 (6) Ethanol 3.0 (7) Polyoxyethylene polyoxypropylene decyl tetradecyl ether 0.5 (8) Compound 1a 0.1 (9) Glycine 0.5 (10 ) Purified water Remaining amount (11) Preservative Suitable amount (12) Perfume Suitable amount

[0027]

Table 7 Example 4 (Emulsion) (Composition) (%) (1) Polyoxyethylene sorbitan tristearate 1.0 (2) Glyceryl oleate 1.0 (3) Glyceryl monostearate 0.5 (4 ) Squalane 6.0 (5) Glyceryl trioctanoate 2.0 (6) Cetyl octanoate 2.0 (7) Stearyl alcohol 2.0 (8) Octyl methoxycinnamate 2.0 (9) 1,3-butylene Glycol 5.0 (10) Glycerin 3.0 (11) Compound 1b 0.1 (12) Nicotinic acid amide 1.0 (13) Purified water remaining amount (14) Preservative appropriate amount (15) Perfume appropriate amount

[0028]

Table 8 Example 5 (Toilet lotion) (Composition) (%) (1) 1,3-butylene glycol 6.0 (2) Glycerin 4.0 (3) Sodium hyaluronate 0.1 (4) Ethanol 5 0.0 (5) Polyoxyethylene-oleyl ether (20 E.O.) 0.3 (6) Disodium edetate 0.1 (7) Sodium citrate 1.0 (8) Compound 1b 0.05 (9) Ammonium chloride 0.5 (10) L-ascorbic acid phosphate magnesium 3.0 (11) Purified water residual amount (12) Preservative appropriate amount (13) Perfume appropriate amount

[0029]

Table 9 Example 6 (Cream foundation) (Composition) (%) (1) Dimethylpolysiloxane (6cs) 10.0 (2) Methylphenylpolysiloxane 3.0 (3) Octamethylcyclotetrasiloxane 10. 0 (4) polyoxyalkylene-modified silicone 5.0 (5) titanium oxide 5.0 (6) sericite 2.0 (7) talc 3.0 (8) red iron oxide 0.4 (9) iron oxide yellow 7 (10) Iron oxide black 0.1 (11) Glycerin 5.0 (12) Compound 1c 0.1 (13) 6-amino-n-caproic acid 0.5 (14) Purified water Remaining amount (15) Preservative Agent proper amount (16) Perfume proper amount

[0030]

Table 10 Example 7 (pack) (composition) (%) (1) dipropylene glycol 3.0 (2) polyethylene glycol 3.0 (3) 1,3-butylene glycol 1.0 (4) glycerin 2 0.0 (5) Sodium pyrrolidonecarboxylate 1.0 (6) Compound 1b 0.05 (7) Lactic acid 0.5 (8) Sodium lactate 0.5 (9) Polyvinyl alcohol 12.0 (10) Ethanol 3.0 (11) Polyoxyethylene polyoxypropylene decyl tetradecyl ether 0.3 (12) Purified water remaining amount (13) Preservative proper amount (14) Perfume proper amount

[Brief description of drawings]

FIG. 1 shows the effect of compound 1a on the intracellular uptake of radioactive thiouracil.

Claims (2)

[Claims] 1. The following general formula (1): A whitening agent comprising a compound represented by the formula: wherein R ¹ and R ² each represent a hydroxyl group, a lower alkoxy group or a sulfuric acid residue, or a salt thereof. 2. A skin cosmetic containing the compound (1) according to claim 1.