JP2502318B2 - Whitening cosmetics - Google Patents

Description

TECHNICAL FIELD The present invention relates to a whitening cosmetic composition, and more particularly to a whitening cosmetic composition containing hydroxystilbene as an active ingredient.

(Problems to be Solved by the Prior Art and Invention) Generally, when ultraviolet rays from sunlight are applied to the skin, thyroninase activity in the skin causes melanin to be produced and increased remarkably, resulting in blackening of the skin. ing. Therefore, various whitening ingredients have been proposed so far based on the idea that inhibition of tyrosinase activity in the process of melanin production is required to prevent or improve color black.

Conventionally, as these whitening ingredients, ascorbic acids,
Hydrogen peroxide and a group of sulfur compounds such as glutathione are known.

However, these whitening ingredients have poor stability in the formulation system, for example, coloring and off-flavor due to decomposition, insufficient transdermal absorbability, insufficient efficacy, and further safety problems. Satisfactory results such as the inclusion of certain substances have not yet been obtained.

(Means for Solving Problems) Therefore, in view of the above-mentioned situation, the present inventors have searched and examined many natural products and synthetic compounds from the viewpoint of thyrodinase activity inhibitory effect in order to solve these problems. Although there was no effect of inhibiting tyrosinase activity, it was discovered that its related compound, 4-hydroxystilbene, had that effect. As a result of further research, it was found that the polyhydroxystilbene represented by the general formula (I) described later has a strong tyrosinase activity inhibitory effect, and it was excellent when it was contained in a cosmetic base at a certain concentration or more. It has been found that the whitening effect is exhibited and the present invention has been completed.

That is, the invention has the general formula (I) (Wherein n is the number 0, 1, 2, 3 or 4 and m is the number 0, 1, 2, 3, 4 or 5) is contained as an active ingredient. A featured whitening cosmetic composition.

It is essential that the polyhydroxystilbene compound represented by the general formula (I) applied to the present invention has a stilbene structure having a phenolic hydroxyl group at the 4-position. As long as this condition is satisfied, almost all stilbene compounds can be used. Specific examples include 4-hydroxystilbene, 2,4-dihydroxystilbene, 3,4-dihydroxystilbene, 4,4'-dihydroxystilbene, 2,4,4'-trihydroxystilbene, 3,4,4'- Trihydroxystilbene, 2 ', 4',
4-trihydroxystilbene, 3 ', 4,4'-trihydroxystilbene, 3'4,5'-trihydroxystilbene, 2,3', 4-trihydroxystilbene, 2 ', 3,4
Trihydroxystilbene, 2,2 ', 4-trihydroxystilbene, 2'4,4', 5'-tetrahydroxystilbene, 2,3 ', 4,5'-tetrahydroxystilbene, 2,
2 ', 4,4'-tetrahydroxystilbene, 3,3', 4,5 '
-Tetrahydroxystilbene, 2 ', 3,4,4'-tetrahydroxystilbene, 3,3', 4,4'-tetrahydroxystilbene, 3,3 ', 4,5,5'-pentahydroxystilbene, 2 , 2 ', 4,4', 6'-pentahydroxystilbene, 2 ', 3,4,4', 6'-pentahydroxystilbene and the like can be mentioned, and one kind or a mixture of two or more kinds thereof is used. It is a thing. In particular, 2,3 ', 4,5'-tetrahydroxystilbene and 3,3', 4,5'-tetrahydroxystilbene are most effective.

There are various methods for synthesizing the polyhydroxystilbene compound applied to the present invention, but the effect is particularly high.
2,3 ', 4,5'-tetrahydroxystilbene, 3,3', 4,
An example of the synthesis of 5'-tetrahydroxystilbene is shown below.

Synthesis Example 1. Wit of 2,3 ', 4,5'-tetrahydroxystilbene 3,5-dihydroxybenzyltriphenylphosphonium salt and 2,4-dihydroxybenzaldehyde
It was synthesized by the tig reaction. [E.Reimann “Tetrahedron
Letters "47, 4051 (1970) refer] ¹ H NMR δ values ppm and coupling constant (CD ₃ COC
_{D 3) 6.45 (J = 2.2Hz} , C 3 -H) 6.39 (J = 2.2,8.5Hz, C 5 -H) 7.42 (J = 8.5Hz, C 6 -H) 6.90 (J = 16.3Hz, C 7 -H) 7.35 (J = 16.3Hz, C 8 -H) 6.53 (J = 2.2Hz, C 2 ', 6'-H) 6.25 (J = 2.2Hz, C4'-H) 13 C NMR δ value ppm ( CD ₃ COCD ₃ ) 117.68 (C ₁ ), 157.32 (C ₂ ), 104.09 (C ₃ ), 159.52 (C ₄ ), 108.88 (C ₅ ), 128.68 (C ₆ ), 124.77 (C ₇ ), 126.70 (C ₈ ), 142.09 (C ₁ ′), 105.91 (C ₂ ′, 6 ′) 159.95 (C ₃ ′, 5 ′) 102.72 (C ₄ ′) Synthesis example 2, 3, 3 ′, 4,5 ′ -tetrahydroxy Wit of stilbene 3,5-dihydroxybenzyltriphenylphosphonium salt and 3,4-dihydroxybenzaldehyde
It was synthesized by the tig reaction. [E.Reimann “Tetrahedron
Letters "47, 4051 (1970) refer] ¹ H NMR δ values ppm and coupling constant (CD ₃ COC
_{D 3) 7.05 (J = 1.9Hz} , C2-H), 6.79 (J = 8.1Hz, C 5 -H) 6.81 (J = 1.9,8.1Hz, C 6 -H), 6.80 (J = 16.1Hz, C _{7 -H), 6.91 (J =} 16.1Hz, C 8 -H), 6.51 (J = 2.2Hz, C 2 ', 6' -H) 6.25 (J = 2,2Hz, C 4 '-H) 13 C NMR δ value ppm (CD ₃ COCD ₃ ) 132.9 (C ₁ ), 116.1 (C ₂ ), 146.0 (C ₃ ), 146.2 (C ₄ ), 113.7 (C ₅ ), 119.8 (C ₆ ), 126.8 (C ₇ ). ), 129.6 (C ₈ ), 140.7 (C ₁ ′), 105.5 (C ₂ ′ _{, 6} ′), 159.5 (C ₃ ′ _{, 5} ′), 102.5 (C ₄ ′) The same applies to other compounds. Can be synthesized by the Wittig reaction between the phosphonium salt and the corresponding aldehyde.

In the whitening cosmetic composition of the present invention, one or more of the above polyhydroxystilbenes can be selected and used. The blending amount thereof is 0.00001 to 1% by weight, preferably 0.00005 to 0.5% by weight, based on the total weight of the cosmetic ingredients. 0.00001
If it is less than 1% by weight, the percutaneous absorption does not reach the optimum amount for exhibiting a whitening effect even if the whitening cosmetic composition of the present invention is applied to the skin, while if it is more than 1% by weight, it is unnatural due to excessive inhibition of tyrosinase activity. It should be avoided as it tends to give the skin a decolorizing effect.

Next, polyhydroxystilbene
In order to demonstrate the effect of the improvement, the results of experiments on the inhibitory effect on tyrosinase, an enzyme involved in the biosynthesis of melanin, are described below including the experimental conditions.

The enzyme tyrosinase used was an enzyme extracted from Harding-Passay mouse melanoma. Enzyme activity absorbs the amount of dopachrome produced using L-dopa as a substrate.
According to the photometry method, the absorbance was measured. The test substance polyhydroxystilbene was prepared by solubilizing 0.1M phosphate buffer solution to a predetermined concentration with a fixed amount of nonionic surfactant (final concentration 0.25%). Add 0.2 ml of enzyme solution, 37 ℃
Incubate for 10 minutes. 1.0 ml of 5 mM L-dopa solution pre-incubated at 37 ° C was added to this reaction mixture and reacted for 10 minutes, and the production of dopachrome was measured with a spectrophotometer as an increase in absorbance at 475 nm with time. Increment in absorbance of control solution without sample (Ac)
Then, the inhibition rate was calculated from the increment (As) of the absorbance of the reaction solution containing the sample.

The values for the single substance obtained in the experiment conducted as described above are shown in Table-1.

The results demonstrate that polyhydroxystilbene inhibits tyrosinase activity and reduces dopachrome production.

When the polyhydroxystilbene compound compounded in the whitening cosmetic composition of the present invention is compounded in the base of the whitening cosmetic composition, these may be used alone or together with other reducing skin-blackening preventing substances.

As described above in detail, the present invention relates to a whitening cosmetic in which a polyhydroxystilbene compound is effectively blended as a component for preventing and improving the darkness of the skin. Compared with cosmetics containing whitening substances such as hydrogen oxide and glutathione, it is possible to far prevent the blackening of the skin caused by the irradiation of ultraviolet rays from the sun, the prevention of dark skin, stains and freckles, and the effect of beautiful skin. It has excellent effects and can be safely used without any harmful effect on the skin.

Here, using the whitening cosmetic composition of the present invention, a whitening effect, a stain,
The effect of improving freckles was examined and also compared with conventional whitening cosmetics. As an application method, 30 women aged 32 to 48 who suffer from dark blacks, stains, and freckles were selected, and these were randomly divided into 3 groups (10 people each), and the 1st group had the whitening of Example 1 described later. A lotion, a whitening lotion in which 2,3 ′, 4,5′-tetrahydroxystilbene in Example 1 was replaced with oxidized glutathione in the second group, and a third group in Example 1 was used. of 2,
Have the control lotion from which 3 ', 4,5'-tetrahydroxystilbene was removed (increased the amount of water) be used continuously in the morning, noon and evening 3 times a day for 3 months, The improvement status of black, stains and freckles was reported after 3 months.

 The results are shown in Table-2.

The results shown in Table 2 demonstrate that the improvement effect in the first group using the product of the present invention is significantly superior to the second group and the third group using the comparative product. . This shows that the hydroxystilbene contained in the whitening cosmetic composition according to the present invention effectively exhibits the whitening effect by the tyrosinase activity inhibitory action and the melanin pigment decolorizing action.

Next, examples of the whitening cosmetic composition of the present invention will be shown. The mixing ratio is parts by weight.

Example 1. Whitening lotion Ethanol 10.0 Propylene glycol 5.0 Polyoxyethylene (50) Hydrogenated castor oil 0.5 Citric acid 0.015 Sodium citrate 0.1 Methylparaben 0.05 2,3 ', 4,5'-Tetrahydroxystilbene 0.0005 Fragrance Purified water 84.3 Example 2. Whitening Makeup Oil Squalane 49.9 Castor Oil 49.9 3,3 ', 4,5'-Tetrahydroxystilbene 0.001 Butylhydroxytoluene 0.001 Fragrance Suitable amount Example 4. Whitening emulsion Oil phase Vaseline 1.0 Whale wax 1.0 Squalane 5.0 Jojoba oil 1.0 3 ', 4,5'-Trihydroxystilbene 0.005 Sorbitan monostearate 1.0 Polyoxyethylene (25) monostearate 2.0 Aqueous phase Carboxyvinyl polymer 0.2 Triethanolamine 0.5 Propylene glycol 5.0 Perfume / preservative Suitable amount Purified water 83.3 Implementation Example 5. Whitening pack Polyvinyl alcohol 20.0 eta Nole 20.0 2,3 ', 4,5'-Tetrahydroxystilbene 0.002 Glycerin 5.0 Perfume Suitable amount Purified water 55.0 Example 6. Solid foundation talc 25.0 Sericite 25.0 Nylon powder 3.0 Titanium mica 3.0 Titanium oxide 8.0 Iron oxide 1.5 Preservative 0.2 Silicone Oil 4.0 Octidodecyl oleate 10.0 2,3 ', 4,5'-Tetrahydroxystilbene 0.001 3,4-Dihydroxy-3', 5'-diacetoxystilbene 0.01 Fragrance Suitable amount Pearling agent 20.0

Claims (2)

(57) [Claims] 1. A general formula (I) as a whitening substance. (Where n is a number 0, 1, 2, 3 or 4 and m is 0,
The numbers 1, 2, 3, 4 or 5 are indicated. ) 1 or 2 or more types of hydroxy stilbene represented by these are contained, The whitening cosmetic characterized by the above-mentioned. 2. The whitening cosmetic composition according to claim 1, wherein the amount of the hydroxystilbene compounded is 0.00001 to 1% by weight based on the entire cosmetic composition.