JPH08283116A - 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 1,3-diarylindan-2-carboxylic acid. CONSTITUTION: A 1,3-diarylindan-2-carboxylic acid of the formula [when R<1> is H, 3,4-methylenedioxy or, 4-methoxy; R<2> is H, 5-hydroxy or, 5-n-propoxy; R<3> is H, 3,4-methylenedioxy, 4-methoxy or, 2-carboxymethoxy) is used. The compound of the formula is formulated to the skin cosmetic preferably in an amount of 0.0001-10wt.%. This skin lightener inhibits the melanin formation in melanocytes to prevent and improve the melanin pigmentation. Further, the formulation of glycyrrhizin, ascorbic acid derivative 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). The inventors have found that 1,3-diallylindane-2-carboxylic acids exhibit substantial skin pigmentation prevention / improvement effects and have excellent skin whitening effects, and have completed the present invention.

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

[0010]

Embedded image

[Wherein R ¹ represents a hydrogen atom, a 3,4-methylenedioxy group or a 4-methoxy group, R ² represents a hydrogen atom, a 5-hydroxy group or a 5-n-propoxy group, and R 2 ³ is a hydrogen atom, 3,4-methylenedioxy group, 4
-A methoxy group or a 2-carboxymethoxy group is shown. ]

1,3-diallylindane represented by
It is intended to provide a whitening agent comprising a 2-carboxylic acid and a skin cosmetic containing the compound.

The 1,3-diallylindane-2-carboxylic acid (1) used in the present invention is a known compound (Jou
rnal of Medicinal Chemist
ry, 1994, Vol. 37, No. 11,1553
-1557), but nothing was known about this inhibition of melanin production.

In the present invention, among the 1,3-diallylindane-2-carboxylic acids represented by the general formula (1), R ¹ is 3,4-methylenedioxy group and R ² is 5
-N-propoxy group, R ³ is a 2-carboxymethoxy group, R ¹ is a 4-methoxy group, R ² is a hydrogen atom,
R ³ is a 3,4-methylenedioxy group, R ¹ is a 3,4-methylenedioxy group, R ² is a 5-hydroxy group, R ³ is a 4-methoxy group, and R ¹ is Three
Particularly preferred is a 4-methylenedioxy group, R ² is a 5-n-propoxy group, and R ³ is a 4-methoxy group.

In the skin cosmetic of the present invention, the amount of 1,3-diallylindane-2-carboxylic acid (1) is 0.0001-
It is preferable to add 10% by weight, particularly 0.001 to 5% by weight.

Further, the skin cosmetic of the present invention has the above-mentioned 1,
3-diallylindane-2-carboxylic acid (1),
Various optional ingredients used in ordinary cosmetics, quasi drugs, pharmaceuticals, etc., such as oils, humectants, thickeners, preservatives, emulsifiers, pigments, powders, pH adjusters, antioxidants, fragrances, emulsifiers 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

In addition, 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.

[0020]

The whitening agent of the present invention comprising 1,3-diallylindane-2-carboxylic acid (1) exhibits excellent melanin pigmentation prevention / improvement 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 caused by sunburn and the like.

[0021]

EXAMPLES The present invention will be described in more detail below with reference to examples, but the present invention is not limited thereto. The following samples were used as the samples in the following examples. Compound-a: In the general formula (1), R ¹ = 3,4-methylenedioxy group, R ² = 5-n-propoxy group, R ³ =
2-Carboxymethoxy group. Compound-b: R ¹ = 4-methoxy group, R ² = H, R ³ = 3,4-methylenedioxy group in the general formula (1). Compound-c: In the general formula (1), R ¹ = 3,4-methylenedioxy group, R ² = 5-hydroxy group, R ³ = 4-
Of methoxy group. Compound-d: In the general formula (1), R ¹ = 3,4-methylenedioxy group, R ² = 5-n-propoxy group, R ³ =
4-methoxy group.

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.

[0024]

[Table 1]

[Results] As shown in Table 2, by visual inspection of the color tone of the cell pellet, clear whitening of the 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.

[0026]

[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 : Sample application site before application L ′ * ₀ : Sample unapplication test 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

[0030]

[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.

[0032]

[Table 4]

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

[0034]

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) Compound-a 1.0 (17) Glycine 0.5 (18) Methyl paraoxybenzoate 0.1 (19) Ion-exchanged water Part

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

[0036]

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) Compound-b 0.01 (12) Arbutin 0.01 (13) Ion-exchanged water The 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.

[0038]

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) Disodium edetate 0.1 (14) Compound-c 0.5 (15) Citric acid Sodium 1.0 (16) Methylparaben 0.1 (17) Ion-exchanged water balance

(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.

[0040]

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) Compound-d 0.05 (12) Ethanol 5.0 (13) Methyl paraoxybenzoate 0.1 (14) Polyoxyethylene polyoxypropylene decyl tetradecyl ether 0.3 (15) Purified water balance

(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.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical display location A61K 31/36 ADA A61K 31/36 ADA C07C 61/39 9450-4H C07C 61/39 62/32 9450 -4H 62/32 62/34 9450-4H 62/34 C07D 317/64 C07D 317/64 // C07M 7:00

Claims (2)

[Claims] 1. The following formula (1): [In the formula, R ¹ represents a hydrogen atom, a 3,4-methylenedioxy group or a 4-methoxy group, R ² represents a hydrogen atom, a 5-hydroxy group or a 5-n-propoxy group, and R ³ represents a hydrogen atom. An atom, a 3,4-methylenedioxy group, a 4-methoxy group or a 2-carboxymethoxy group is shown. ] A whitening agent comprising 1,3-diallylindane-2-carboxylic acid represented by 2. A skin cosmetic containing the 1,3-diallylindene-2-carboxylic acid according to claim 1.