JPH08283118A - Skin lightener - Google Patents

Abstract

PURPOSE: To obtain a skin lightener and a skin cosmetic which have excellent skin-lightening effect and can prevent and treat skin spots and ephelis caused by sun burn by using a specific stachybocin. CONSTITUTION: A stachybocin of formula I (R<1> , R<2> are each H, OH) is used. The compound of formula I includes stachybocin A of formula II, stachyboci B of formula III and stachyboci C of formula IV. A stachybocin of formula I is formulated to the skin cosmetic in an amount of 0.0001-10wt.%. The skin lightener inhibits the melanin formation in melanocytes to reveal excellent prevention against and improvement of the melanin pigmentation. Further, the formulation of allantoin, kojic acid, an oil component of adlay and the like can increase the melanin pigmentation-suppressing effect. The addition of a variety of UV-ray absorbers also can improve the sun-tan prevention effect.

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 whitening cosmetic having an excellent skin whitening effect and capable of preventing and treating spots and freckles caused by sunburn and the like.

[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.

Further, it is considered that the delay of keratinization of epidermal keratinocytes (keratinocytes) with aging 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.

Therefore, 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, cosmetics containing a vitamin C (L-ascorbic acid) derivative having excellent reducing ability have been used. However, this also has a drawback in that the stability is difficult and the effect is hardly recognized when used externally.

On the other hand, in Europe and America, hydroquinone is used as a medicine for treating spots and whitening black skin, but these also have a problem in safety (irritation, allergy) of the substance itself, Further, there is a problem in compounding it as a drug in that it may cause vitiligo. In addition, various external skin preparations such as isoflavone derivatives (Japanese Patent Laid-Open No. 58-225004) and
A p-hydroxycinnamic acid derivative as a cinnamic acid derivative (JP-A-59-196813) and the like are known.

[0006]

However, at present, no substance has been known which has a substantial effect of preventing / improving pigmentation and an excellent compoundability with a cosmetic base.

Therefore, it has been desired to develop a whitening agent having a skin whitening effect and capable of preventing and treating spots and freckles caused by sunburn and the like.

[0008]

Under these circumstances, the present inventors have conducted extensive studies to obtain a substance that reduces or eliminates pigmentation through research on the mechanism of melanin production, and as a result, it is represented by the following general formula (1). Stakibosin (St
The present inventors have found that achybocins) have a substantial skin pigmentation preventing / ameliorating effect and an excellent skin whitening effect, and have completed the present invention.

That is, the present invention provides a whitening agent consisting of stakibocines represented by the following general formula (1) and a skin cosmetic containing the compound.

[0010]

Embedded image

[In the formula, R ¹ and R ² each represent a hydrogen atom or a hydroxyl group]

Stakibosin used in the present invention (1)
Is a Stachybotr separated from cultivated land in Yamanashi Prefecture
ys sp. A component isolated from M6222, which is a known compound ["a novel endothelin antagonist Stachybo
Structure determination of cins ", 36th Annual Meeting of Natural Organic Compounds (1994)], but it was not known at all that this suppressed melanin production.

The stakibocines used in the present invention include stakibosin A, B and C having the following structural formulas.

[0014]

Embedded image

[0015]

[Chemical 4]

[0016]

Embedded image

In the skin cosmetic of the present invention, stakibocines (1) are contained in an amount of 0.0001 to 10% by weight, and particularly 0.001 to
It is preferable to add 5% by weight.

Further, in the skin cosmetic of the present invention, in addition to the above-mentioned stakibocines (1), various optional components used in ordinary cosmetics, quasi drugs, pharmaceuticals, etc., such as oils, moisturizers, thickeners, etc. Agents, preservatives, emulsifiers, pigments, powders, pH adjusters,
Antioxidants, fragrances, emulsion stabilizers 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, electrolytes such as sodium chloride and potassium chloride, and preservatives such as 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. To be

Also, as various active ingredients, allantoin, vitamin E derivative, glycyrrhizin, ascorbic acid derivative, kojic acid, arbutin, pantethenic acid derivative, placenta extract, anti-inflammatory agent, yoquinin, various plant extracts, etc. should be added. Thereby, the melanin suppressing effect can be improved. Furthermore, the addition of various ultraviolet absorbing substances can improve the sunburn preventing effect.

The skin cosmetics to which the present invention is applied are not limited to general skin cosmetics, but include medicated cosmetics and the like. The skin cosmetics of the present invention can be prepared in various forms by conventional methods, but generally they are lotions, emulsions, creams, ointments, sticks, solutions with organic solvents, packs, gels. It is preferable to have a shape.

[0022]

EFFECTS OF THE INVENTION The whitening agent of the present invention comprising stachybosin (1) exhibits excellent melanin pigmentation preventing / ameliorating effect by suppressing melanin production of melanocytes,
Skin cosmetics containing the compound exhibit an excellent skin whitening effect and are extremely useful for the prevention and treatment of spots and freckles due to sunburn and the like.

[0023]

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: According to the following test method, samples of various concentrations were added to a culture plate of normal human melanocytes to examine the effect on cell melanin production. The results are shown in Table 2.

[Test Method] Normal human melanocytes commercially available from Clontex Co., Ltd. were subcultured according to a conventional method and subjected to the present test. A sample 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 evaluated by collecting cells at a sample concentration of 10 μM, visually observing the color tone of the cell pellet, and assigning evaluation points of 1 to 4. The color tone was determined according to the criteria shown in Table 1 below. The evaluation was shown by the average of the evaluation points of 10 culture plates. Further, in the determination of the color tone, as a control, the solvent used for dissolving the sample was added to the culture solution so as to have the same concentration, and this was used.

[0026]

[Table 1]

[Results] As shown in Table 2, by visual inspection of the color tone of the cell pellet, clear whitening of cells was observed at a concentration of 0.01 μM or more. From the above results, an inhibitory effect on the melanin production of cultured human melanocyte-producing cells was confirmed.

[0028]

[Table 2]

Example 2 Extinction effect of UV-B pigment spots on the back of brown guinea pigs: The extinction effect on UV-B pigment spots was examined according to the following test method. The results are shown in Table 4.

[Test Method] The back hair of 20 brown guinea pigs was carefully shaved with a hair clipper and a shaver, and then U
Double the amount of UV rays in the VB region to the minimum erythema dose (MED)
Irradiate once a day for 3 days to induce pigment spots 2 times a day
Once, the amount of pigment spot extinction was examined by continuously applying a 1 wt% concentration sample to the test site for 1 month. For evaluation, the L * value was calculated from the Munsell value obtained by measuring with a color difference meter, and the ΔL * (change with time) of the sample-coated portion was changed to the ΔL * (change with time of the sample) where the sample was not applied (solvent only = control). )
The value (ΔΔL *) obtained by subtracting In addition, ΔΔL * is expressed by the following formula, and the result is shown as an average value of the evaluation points of 20 test animals.

ΔΔL * = (L * ₁ −L * ₀ ) − (L ′ * ₁ −L ′ * ₀ ) L * ₀ : Test site for applying sample before application L ′ * ₀ : Test for not applying sample before application Site L * ₁ : Sample application test site 1 month after continuous application L '* ₁ : Sample non-application test site 1 month after continuous application

[0032]

[Table 3]

[Results] As shown in Table 4 below, clear discoloration of pigment spots was observed by application of this sample as compared with the control.

[0034]

[Table 4]

From the above results, it was revealed that this sample has a melanin production and a fading effect on UV-B-induced pigment spots, suggesting its usefulness as a whitening agent.

[0036]

Table 3 Example 3 (Emulsion) (Composition) (wt%) (1) Polyoxyethylene sorbitan tristearate 1.0 (2) Glycerol oleate 1.0 (3) Glycerin monostearate 0.5 ( 4) Squalane 5.0 (5) Glyceryl trioctanoate 2.0 (6) Dimethylpolysiloxane (50cs) 0.2 (7) Cetyl octanoate 1.5 (8) Stearyl alcohol 2.0 (9) Methoxycinnamate Octyl acid 2.0 (10) Butyl paraoxybenzoate 0.1 (11) 1,3-Butylene glycol 5.0 (12) Glycerin 3.0 (13) Xanthan gum 0.2 (14) Tetrasodium edetate 0. 1 (15) Sodium citrate 1.0 (16) Stakivocin A 1.0 (17) Glycine 0.5 (18) Methyl paraoxybenzoate 0.1 (19) Ion exchange Water balance

(Preparation Method) The oil phase components (1) to (10) heated and dissolved at 80 ° C. were added to the aqueous phase components (11) to (19) heated to 80 ° C. with stirring to emulsify. Then, cool to room temperature with stirring.

[0038]

Table 4 Example 4 (Toilet lotion) (Composition) (% by weight) (1) 1,3-butylene glycol 8.0 (2) Glycerin 4.0 (3) Xanthan gum 0.1 (4) Sodium chondroitate 0.1 (5) Sodium hyaluronate 0.1 (6) Ethanol 3.0 (7) Methyl paraoxybenzoate 0.1 (8) Polyoxyethylene-oleyl ether (20E.O.) 0.5 (9) Tetrasodium edetate 0.1 (10) Sodium citrate 1.0 (11) Stakibosin B 0.01 (12) Arbutin 0.01 (13) Ion-exchanged water balance

(Preparation method) After stirring and dispersing the components (1) to (5), 65 parts of ion-exchanged water (13) is added to make A. After stirring and dissolving (6) to (8), the remaining amount of ion-exchanged water (13) is added and designated as B. After stirring A and adding B to make the mixture uniform, components (9) to (12) are added and dissolved by stirring.

[0040]

Table 7 Example 5 (Cream foundation) (Composition) (wt%) (1) Methylpolysiloxane (6cs) 10.0 (2) Methylphenylpolysiloxane 3.0 (3) Octamethylcyclotetrasiloxane 10 0.0 (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 0 7 (10) Iron oxide black 0.1 (11) Butylparaben 0.1 (12) Glycerin 5.0 (13) Edetate disodium 0.1 (14) Stakivocin C 0.5 (15) Sodium citrate 1.0 (16) Methylparaben 0.1 (17) Ion-exchanged water Remainder

(Preparation method) The components (1) to (11) were added to 8 parts.
While heating and dissolving at 0 ° C and stirring, an aqueous phase in which the components (12) to (17) were dissolved and heated at 80 ° C was added and uniformly emulsified.

[0042]

Table 8 Example 6 (pack) (Composition) (wt%) (1) Dipropylene glycol 3.0 (2) Polyethylene glycol 3.0 (3) 1,3-Butylene glycol 1.0 (4) Glycerin 2.0 (5) Sodium pyrrolidonecarboxylate 1.0 (6) Sodium citrate 1.0 (7) Disodium edetate 0.1 (8) Lactic acid 0.5 (9) Polyvinyl alcohol 12.0 (10) Kojic acid 0.05 (11) Stakibosin A 0.05 (12) Ethanol 5.0 (13) Methyl paraoxybenzoate 0.1 (14) Polyoxyethylene polyoxypropylene decyl tetradecyl ether 0.3 (15) Purification Remaining water

(Preparation Method) The components (1) to (8) were dissolved by stirring with 50 parts of ion-exchanged water (15) to give A.
After stirring and dissolving the components (12) to (14), the remaining amount of ion-exchanged water (15) is added to homogenize the mixture to give B. (9) to (11) were added to A while stirring, and the mixture was uniformly dispersed, and then heated and dissolved at 70 ° C. This is cooled to 45 ° C., B
Add to homogenize and cool to room temperature.

Claims (2)

[Claims] 1. A whitening agent comprising a stachybosin represented by the following general formula (1). Embedded image [In the formula, R ¹ and R ² each represent a hydrogen atom or a hydroxyl group] 2. A skin cosmetic containing the stakibosin according to claim 1.