JPH04149114A - Whitening cosmetic - Google Patents

Abstract

PURPOSE:To obtain a whitening cosmetic excellent in whitening effect and preservability in storage thereof by blending an ascorbic acid derivative. CONSTITUTION:An ascorbic acid derivative of formula I or II [R1 and R2 are group of formula III (R3 and R4 are H or CH3; R5 is 1-20C hydrocarbon or R6-A-R7 group; R6 and R7 are 1-12C hydrocarbon; A is O, CO, CH(OH), etc.] is used in an amount of 0.1-10wt.%, and a perfume, a preservative, a pigment, a skin-nutritive substance, etc., are suitably blended therewith to obtain the objective cosmetic. As the cosmetic form, cream, emulsion, lotion, powder, etc., are available. Since the ascorbic acid derivative is contained, a high tyrosinase-inhibitory effect, an excellent inhibitory effect on melanin formation and an excellent effect on recovery of brightness of the skin color are shown.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel whitening cosmetic. For more details,
This invention relates to a skin whitening makeup product 4 that is characterized by containing a vitamin C-E derivative and has excellent whitening effects and storage stability.

[Prior art] Spots and freckles in general 3 It is believed that the pigmentation of the skin, which is seen due to sunburn, is due to the fact that dirosine present in the skin is oxidized to melanin by the action of tyrosinase, and this melanin is produced in excess. has been done.

Conventionally, ascorbic acid has been used for the purpose of preventing or treating pigmentation.

However, ascorbic acid is extremely unstable to heat and light, and is susceptible to oxidation, especially in water-based cosmetics.
It decomposes and causes odor and discoloration.

In order to solve these problems, we developed ascorbic acid higher fatty acid ester, ascorbic acid sulfate ester, L-ascorbic acid phosphate magfusium 1, tocopherol-L-
Various ascorbic acid derivatives such as ascorbic acid 2-phosphate and tocopherol-disascorbic acid 6-dicarboxylic acid diester are used.

However, although ascorbic acid higher fatty acid ester has improved stability, it has a weak whitening effect.

Ascorbic acid sulfate is water-soluble, so it is difficult to incorporate into oil-based cosmetics and has a weak whitening effect. Magnesium ascorbic acid phosphate has an excellent whitening effect, but has poor skin permeability. Therefore, in order to obtain a whitening effect, the amount of compounding ingredients must be increased.

Tocopherol-I, -ascorbic acid-2-phosphate salts are difficult to formulate because some salts are insoluble in water, depending on the type of salt.

Tocopherol-shi-ascorbic acid-6-dicarboxylic acid diester has been proposed to overcome the drawbacks of item F (Japanese Patent Application Laid-Open No. 62187470). However, although this compound has increased oil solubility of vitamin C and has a high whitening effect, it has the problem that it is easily decomposed during storage and its activity is significantly reduced.

[Problems to be Solved by the Invention] Therefore, an object of the present invention is to provide a whitening cosmetic that has excellent whitening effects, improved solubility of vitamin C, and excellent storage stability of vitamin C. It is in.

[Means to solve problems]

The present invention provides: (1) A whitening cosmetic comprising an ascorbic acid derivative represented by the following general formula (1) or (II).

OH ○1 (Two (II) Medium R teeth, , R,, R, represents H or CHs.

R6 represents a linear or branched, saturated or unsaturated hydrocarbon group having 1 to 20 carbon atoms, or a -R, -A-R, - group; ~12 linear or branched, saturated or unsaturated hydrocarbon groups, A is -〇-7-C
o-, -0CO--CH(CH) CH(NRs Rq) -1NR1゜-NR,, -C
Represents either O-.

Moreover, Re-R++ represents either H1 lower alkyl group, aliphatic lower anru group, or aromatic acyl group. ) (2) Characterized by containing an ascorbic acid derivative represented by the following general formula (III) or (TV) (provided that R, , R, are the same as in (r) and (II)) ).

Ascorbic acid m8 bodies represented by general formulas (1) to (IV) used in the present invention can be produced, for example, as follows.

Acid halide totocopherol of halocarboxylic acid,
The reaction is carried out in the presence of a base such as pyridine in a non-reactive solvent such as ether.

Next, L~ascorbic acid is reacted with acetyl chloride in an acetone solvent, suspended at room temperature, and then cooled. 5.60-isopropylidene-L-ascorbic acid is prepared by washing the obtained crystals with chilled acetone and drying.

The obtained 5,6-0-isopropylidene-A, THF
By reacting in the presence of a base such as potassium carbonate, sodium carbonate, sodium hydroxide monopotassium hydroxide, etc. to synthesize an ether, -C formula (III)
Alternatively, a compound represented by (IV) can be produced.

The compound represented by the general formula (1) or (Il) can be obtained by dissolving the compound (I[I) or (TV) in a solvent such as THF,
Add an acid such as N-hydrochloric acid and stir.
It can be obtained by removing the protecting group at position.

Examples of acid halides of halocarboxylic acids used to produce compounds represented by formulas (1) to (87) include the following:
)3-Y(CH2)2XCH.

), CH CH.

).

(CHf), -C (CH.

(cH.

)h H2 (CH2 ).

II -Y CH.

(CH2 (CH2)2C CH.

(C1(2)SC (CH2)3 II II -Y, X-(C)I, >80-CCCH2'),,
-C-Y.

○H0 (I X-(CH2)2CHCH, -C-Y.

OH0 X-(CH2), C)((CHt')t-c-
Y.

OHC2N5 X-(CH2)SCH(CH,), CH(CH,)SN
(CH3)! 0 (CH2), CH(CH2), -Cx-(CH2)2NH (CH2).

(C11□nicl21=cH (C) (2) SNH (CH,).

CI+10 (CH2)3N (C112), CH=CH(CH2)6-C-YHNC
OCH30 X-(CH2), CHCH2-C, -Y0=C-Ph
○ X-(C)(! )3N (CH2), -C-YC
H3-CO0 The inhibition rate of tyrosinase activity was measured by the method described below, and the results are shown in Table 1.

In addition, the concentration of compounds (]) and (II) in the sample is 2
Weight%.

In the whitening cosmetic of the present invention, the content of the monoascorbic acid derivatives represented by general formulas (1) to (■) is 0.1 to 10% by weight (hereinafter referred to as weight) based on the total amount of the cosmetic. % is abbreviated as wt%) is preferred.

If it is less than 0.1 wt%, it is difficult to obtain the desired effect, and lQ
Even if the amount exceeds wt%, no significant increase in effectiveness can be expected.

The dosage form of the whitening cosmetic of the present invention is not particularly limited, and may be cream, emulsion, or lotion.

Usual cosmetic formulations such as powder can be used.

Further, as other ingredients, fragrances, preservatives, colorants, skin nutrients, etc. may be appropriately incorporated within the scope of achieving the object of the present invention.

〔Example〕

The present invention will be explained below with reference to Examples.

■ Storage stability test (stability of tyrosinase activity inhibition rate) ■ Melanin formation inhibition test ■ Skin color brightness recovery test, and ■ Whitening practical test described in Examples were conducted as follows.

■ Storage stability test Immediately after preparation of the whitening cosmetic of the present invention, 2
After 3 months of storage at 0°C and 3 months of storage at 45°C, the inhibition rate of tyrosinase activity was measured to evaluate storage stability.

Harding-Passa
y) Using the enzyme tyrosinase extracted from mouse melanoma, its enzyme activity was determined by 475n of dopachrome.
This was investigated by photometry, which measures the absorbance of m.

Whitening cosmetics of the present invention (hereinafter referred to as samples) 0.9m,
L-tyrosine solution (0.3 mg/m
1 ml) and Matsukurupain's buffer (pH 6,
After adding 1 ml of 8) and incubating for 10 minutes in a constant temperature water bath at 37°C, tyrosinase solution (1 mg
/ m l ) to 0.1 m jl! Add it, stir well, keep it at 37°C for 10 minutes, and then measure the absorbance at 475 nm (
D+). The absorbance (D2) of a similar reaction using heat-inactivated tyrosinase and the absorbance (D,) of a control test product using only water instead of the sample were measured, and the tyrosinase activity inhibition rate was calculated from the following formula. calculate.

Tyrosinase activity inhibition rate (%) D-Dz ■ Melanin formation inhibition test F] Black guinea pig (male, about 8 years old, average weight 350
g) After cutting the back skin, completely remove the hair with hair removal cream, and from the next day, apply each sample to the skin of the hair-removed area once a day in a 4 cm area.
Each sample was applied in an amount of 0.2 g, and an occluded patch was applied. A group of 10 animals was used for each sample.

The melanin formation inhibitory effect was evaluated one month after the start of the test, and the brightness (Y,) of the applied area was evaluated using a high-speed spectrocolorimeter.
and the brightness (Yo) of the non-applied area■ Skin color brightness recovery test A sample application area and a non-application area were set on the back skin of 20 test subjects, and both areas were exposed to UV-B 9M range. UV rays were irradiated in an amount twice the minimum amount of erythema, and after one week, the standard brightness (VO value, ■.' value) of each skin was measured. Subsequently, the sample was continuously applied to the application site once a day for 3 months.
, 7. Recovery brightness (v, ... value of the skin of the application site and non-application site after 13 weeks).

(a) value) was measured, and skin color recovery evaluation was performed according to the criteria shown in Table 2.

The brightness (V value) of the skin was calculated using the Munsell value obtained by measuring with a high-speed spectrocolorimeter.

The average of the evaluation scores of 20 test subjects (lI calculation, skin table ■ Whitening practical test Samples were applied to the slope of each of 20 test subjects who complained of age spots, freckles, sunburn, etc., once in the morning and once in the evening for 3 months. The improvement effect after continuous application was investigated.Evaluation was expressed by the number of test subjects who answered that their skin freckles and sunburn were improved.

Examples 1-8. Comparative Examples 1 to 4 (Two-layer lotion) Two-layer lotions as Examples and Comparative Examples were prepared by changing the type and content of the L-ascorbic acid derivative as shown in Table 3 in the composition below. I prepared it and conducted a poetry review.

The results are shown in Table 3.

(1) &Il formation (2) iI production method Among the components (A), oil-soluble ones are added to the (B) ingredient (oil phase), and water-soluble ones are added to the (C) ingredient (aqueous phase). , if necessary, heat to dissolve uniformly.

Next, the component solution (B) and the component solution (C) are uniformly mixed, stirred and dispersed, and then filled into a container.

When using, shake and disperse the contents evenly (3)
As shown in Table 3, Comparative Example 1, which does not contain ascorbic acid derivatives, does not inhibit tyrosinase activity, does not inhibit melanin formation (YT/YO<1), and has almost no effect on restoring skin color brightness. The results of the practical test were also poor.
Comparative Example 2 containing L-ascorbic acid magnesium phosphate as an ascorbic acid derivative had good storage stability, but had poor melanin formation inhibiting effect and skin color brightness recovery effect, and the results of practical tests were also poor. .

Comparative Example 3, which contains α-tocopherol-shi-ascorbic acid-6-succinic acid diester as an ascorbic acid derivative, has a somewhat higher melanin formation inhibiting effect and skin color brightness recovery effect than Comparative Example 1.2. Although there are
The storage stability was poor, and the results of practical tests were also poor.

α-tocopherol as an ascorbic acid derivative
In Comparative Example 4 containing ascorbic acid-2-phosphate ester, the melanin formation inhibiting effect 1 skin color brightness recovery effect was also insufficient, and the results of the practical test were also poor.

In comparison, ascorbic acid derivatives have the general formula (1
Examples 1 to 8 containing compounds represented by ) to (IV)
has a high tyrosinase activity inhibition rate, good storage stability, excellent melanin formation inhibiting effect and skin color brightness recovery effect, and also showed good results in practical tests.

Examples 9-16. Comparative Examples 5 to 8 (Skin Cream) Similar to Example 1, various Examples with the following composition,
Comparative skin cream was prepared and various test compositions (2) tA manufacturing method ^) Among the ingredients, oil-soluble ones were mixed into the (B) component, and water-soluble ones were mixed into the (C) component. and (B) component and (
C) Dissolve each component uniformly by heating to bring the temperature to 80°C.Next, pour component (C) into component (B) and mix with stirring, then lower the temperature to 3°C while stirring. (3) Characteristics As shown in Table 4, in contrast to Comparative Examples 5 to 8, Examples 9 to 16, which are whitening cosmetics of the present invention, all showed good results in various tests and had excellent whitening effects.

Examples 17-24. Comparative Examples 9 to 12 (Emulsions) Emulsions of various Examples and Comparative Examples having the following compositions were prepared and various tests were conducted. The results are summarized in Step 5 (2) Preparation Method Among the ingredients in (A), oil-soluble ones are mixed in the (B) ingredient, water-soluble ones are mixed in the (C) ingredient, and the (B) ingredient is mixed in the (C) ingredient. and(
C) Uniformly heat and melt each component to bring the temperature to 80°C. Next, the component (C) was injected into the component (B) and mixed with stirring, and then the temperature was raised to 3 °C while stirring. Examples 17 to 24, which are cosmetics, all showed good results in the poetry test and had excellent whitening effects.

(Effects of the Invention) As described above, the whitening cosmetic of the present invention has the following effects compared to the conventional whitening cosmetic containing an ascorbic acid derivative:
It is clear that it is significantly superior in whitening effect and storage stability.

Claims (2)

[Claims] (1) A whitening cosmetic characterized by containing an ascorbic acid derivative represented by the following general formula (I) or (II). ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(II) (R_1 and R_2 in formulas (I) and (II) are ▲Mathematical formulas, There are chemical formulas, tables, etc. -A-R_7
- group, R_6 and R_7 are linear or branched, saturated or unsaturated hydrocarbon groups having 1 to 12 carbon atoms, A is -
O-, -CO-, -OCO-, -CH(OH)-, -CH(N
R_8R_9)-, -NR_1_0-, -NR_1_1
-CO- represents either. Moreover, R_8 to R_1_1 represent any one of H, a lower alkyl group, an aliphatic lower acyl group, and an aromatic acyl group. ) (2) A whitening cosmetic containing an ascorbic acid derivative represented by the following general formula (III) or (IV). ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(IV) (However, R_1 and R_2 are the same as in the case of (I) and (II). It's the same.