JPH04149113A - Whitening cosmetic - Google Patents

Abstract

PURPOSE:To obtain a whitening cosmetic excellent in whitening effect preservability in storage thereof by containing tocopherol-L-ascorbic acid- dicarboxylic acid diester. CONSTITUTION:A tocopherol-L-ascorbic acid-dicarboxylic acid diester of formula I or II [R1 and R2 group of formula III (R3 is CH2, O, CO, CHNH2, etc.; (x) and (y) are 0-10; R4 and R5 are H and CH3)] 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 whitening cosmetic with excellent whitening effect and storage stability, which is characterized by containing a vitamin C-E derivative.

[Conventional technology]

-C Skin pigmentation seen in spots, freckles, sunburn, etc. is said to be caused by tyrosine present in the skin being oxidized to melanin by the action of tyrosinase, and this melanin being produced in excess.

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 easily oxidized, especially in water-based cosmetics.
It decomposes and causes odor and discoloration.

In order to solve these problems, ascorbic acid esters, ascorbic acid sulfate, L-ascorbic acid phosphate, tocopherol phosphate ester, tocopherol L- Various ascorbic acid derivatives such as ascorbic acid 6-dicarboxylic acid diester are used.

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

Because ascorbic acid sulfate is water-soluble, it is difficult to incorporate into oil-based cosmetics and has a weak whitening effect.

L-ascorbic acid phosphate magnonium has an excellent whitening effect, but its skin permeability is insufficient, so in order to obtain a whitening effect, a large amount of ingredients must be added.

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

To overcome the above-mentioned drawbacks, tocopherol-shi-ascorbic acid-6-dicarboxylic acid diester 1-
17 (Japanese Unexamined Patent Application Publication No. 1983-87470). However, this compound has increased oil solubility of vitamin C,
Although it has a high whitening effect, it has the problem that it easily decomposes upon storage and its activity decreases significantly.

[Problem 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.

[Means to solve problems]

The present invention is directed to a whitening cosmetic containing a tocopherol-ascorbic acid-dicarboxylic acid diester represented by the following general formula (1) or (It).

(formula %formula%() It means,.

represents an integer of 0, r, s, t, u, v represent an integer of 0 to 4, and R6R3 represents H or CH. ) (2) Tocopherol-5,6-0-isopropylidene represented by the following general formula (In) or (rV)
A whitening cosmetic characterized by containing an ascorbic acid-dicarboxylic acid diester.

(However, R,, R, is (]).) Dicarboxylic acids used to produce the same ascorbic acid derivative as in (II) include, for example, oxalic acid, malonic acid, and succinic acid. Acid, glutaric acid, adipic acid, acetic acid.

Melinic acid 1 Schelic acid, azelaic acid, heptanoic acid, 1.9-nonamethylene dicarboxylic acid, 1.10 decamethylene dicarboxylic acid, 1.11-undecamethylene dicarboxylic acid, 1.12-dodecamethylene dicarboxylic acid acid, 1
．． 11-) Ridecamethylene dicarboxylic acid, 1.14-tetradecamethylene dicarboxylic acid, 115-pentadecamethylene dicarboxylic acid, 116-hexadecamethylene dicarboxylic acid, 1.17-butadecamethylene dicarboxylic acid, 1
．． 18-Occudecamethylene dicarboxylic acid, diglycolic acid, acetonocarboxylic acid, fumaric acid, maleic acid, trans-2-butenedicarboxylic acid, trans)/trans-
Examples include muconic acid, traumatic acid, mucic acid, glutamic acid, aspartic acid, 3-methylambic acid, 3-methylglutaric acid, 2,3-nomethyl-Jresuccinic acid, and the like.

Tocopherol-5,6-0-isopropylidene- represented by the general formula Cl1l), (8) used in the present invention
1,-Ascorbic acid dicarboxylic acid diester can be produced, for example, by the following method.

First, L-ascorbic acid is reacted with acetyl chloride in an acetone solvent, suspended at room temperature, and then cooled. The obtained crystals were washed with chilled acetone and dried to give 5.6-0-isopropylidene-L-
Prepare ascorbic acid.

The acid halide of the dicarboxylic acid and the tocopherol are then combined in a non-reactive solvent such as an ether with a suitable base.
For example, add pyridine and react.

The obtained tocopherol dicarboxylic acid ester was
A condensation reaction is carried out with ascorbic acid in which the hydroxyl groups at position and 6 are protected. The reaction is carried out using a dehydrating agent such as dicyclohexylcarbodiimide or thionyl chloride in the presence of a base catalyst such as pyridine.

Tocopherol-56-0 obtained as above
The physical property values of -isopropylidene-L-ascorbic acid-2-succinic acid diester are illustrated.

Elemental analysis; C, 2) 1. ．． 0 Melting point; 114~]15°C IR; 3460 2955.1751cmU■;λ, -
, 211. Inm Co C-NMR (Medium DMS O-
cl,)δ(pp)=11°4, 11.7.12
．． 5. ]9.5.20.0.20.422.322.4
,23.6,23.8,24.1.24.425.42
5.5.25.9, 27.4.28.7.29.030
．． 430.932.1, 33.3, 36.7, 36.8
37.038.9.65.0, 73.9, 74. ,! ,
74.9°109,], 117.4. ]1B,6,1
21.8.124.9126.4, 140.6, 148
．． 8,152.0.170.1170.7.173.0 The -a formula (+), (II) used in the present invention) Kotzerol-monoascorbic acid-dicarboxylic acid diester is the above-mentioned Tocopherol 5,6-0-isopropylidene=L-ascorbic acid dicarboxylic acid diester is dissolved in a solvent such as THF (tetrahydrofuran), and an acid such as 1N hydrochloric acid is added and stirred to dissolve the isopropylidene group at the 5.6-position. can be produced by deaging.

Next, the inhibition rate of thyrononase activity of the compound represented by the general formula (+)iI) is illustrated in Table 1.

The measurement method will be explained in Examples.

In addition, the concentration of the compound (]) in) in the sample is the general range (1) to (rV) in the whitening cosmetic of the present invention.
The content of the ascorbin # derivative represented by is preferably 01 to 10% by weight (hereinafter, weight% is abbreviated as wt%) based on the total amount of the cosmetic.

Q. If it is less than wt%, it is difficult to obtain the desired effect.)
Even if it exceeds 3 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 usual cosmetic dosage forms such as cream, emulsion, gelatinous powder, etc. can be applied.

Other ingredients such as fragrances, preservatives, colorants, skin nutrients, etc. may be added as appropriate 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 (thyronase activity■
(stability of damage rate), (melanin formation inhibition test) (skin color brightness recovery test), (b) skin whitening practical test were conducted as follows.

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

Harding-Pass
ay) 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 cosmetic of the present invention (hereinafter referred to as sample) 0.9ml!
was collected and treated with L-thironne soluble i'ff1 (0.3 mg/m
n) and Manokulhan's buffer (pH 6,
After adding 8') mff and incubating for 10 minutes in a constant temperature water bath at 37°C, tyrosinase solution (1 m
g/mj 0.1 m! ! Add and stir well, 37
After 10 minutes at 4°C, the absorbance (D) was measured at 4.75 nm.
l). Measure the absorbance (D2) of a similar reaction using heat-inactivated tyrosinase and the absorbance (D3) of a control test product using only water instead of the sample, and calculate the tyrononase activity inhibition rate from the following formula. do.

Tyrosonase activity inhibition rate (%) zDt ■ Melanin formation inhibition test Fl black guinea pig (male, approximately 8 cm, average weight 350
After cutting the back skin of g), completely remove the hair with hair removal cream, and from the next day, apply each sample 4 to the skin of the hair removal area once a day for 4 cm.
0.2 g per 2 pieces was applied 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 (Yl) of the applied area was measured using a high-speed spectrocolorimeter.
and the brightness of the non-coated area (Yo) ('l” T /
Yo ) was determined and the melanin formation j suppression rate was determined. ■ Skin color brightness recovery test A sample application site and a non-application site were set on the back skin of 20 test subjects, and ultraviolet rays in the tJV-B region were applied to both sites to minimize erythema. After two weeks, the standard brightness (Vo value 1 to lo' value) of each skin was measured. Subsequently, the sample was continuously applied to the application site once a day for 3 months, and 3.7
．． After 13 weeks, the restored lightness (V, . . . value v7 . . . value) of the skin of the application site and the non-application site was measured, and the recovery of skin color was evaluated according to the criteria shown in Table 2.

In addition, the brightness of the skin (~゛ value) was calculated from the Munsell value obtained by measurement with a high-speed spectrocolorimeter.

The average value of the evaluation scores of 20 test subjects was calculated, and the sample was applied to the faces of 20 test subjects who complained of freckles, sunburn, etc. for 3 consecutive months, once in the morning and evening. The improvement effect after application was investigated. The evaluation was expressed by the number of test subjects who answered that their freckles and sunburn were improved.

Examples 1 to 8, Comparative Examples 1 to 4 (Two-layer lotion) In the following composition, the type and content of the L-ascorbic acid derivative were changed as shown in Table 3, and in the Examples and Comparative Examples. A two-layered lotion was prepared and tested.

The results are shown in Table 3.

(]) Composition (2) Preparation method Among the components (A), oil-soluble ones are necessary in the (B) component (oil phase), and water-soluble ones are necessary in the (C) component (aqueous phase). Heat to dissolve uniformly.

Next, the (B) component solution 1 (C) component solution is uniformly mixed, stirred and dispersed, and then filled into a container.

When using, the contents should be uniformly shaken and dispersed (31 Characteristic 7 Comparative Example 1, which does not contain a scorbic acid derivative, does not inhibit tyronase activity and therefore does not suppress melanin formation (Y, /Yo<1) There was almost no effect on restoring the brightness of skin color, and the results of practical tests were also poor.

Comparative Example 2, which contains magunium L-ascorbic acid sulfate as an ascorbic acid derivative, has good storage stability, but has poor melanin formation inhibiting effect and skin color brightness recovery effect, and the results of practical tests are also poor. It wasn't good.

As an ascorbic acid derivative, α-tocopherol-L
-Comparative Example 3 containing ascorbic acid-6-succinic acid noester has somewhat improved melanin formation suppressing effect and skin color brightness recovery effect compared to Comparative Example 1.2, but
The storage stability was poor, and the results of practical tests were also poor.

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

In comparison, as an ascorbic acid derivative, the general formula (1)
Examples 1 to 8 containing ascorbic acid derivatives represented by ~(rV) have a high thyronase activity inhibition rate,
Moreover, it has good storage stability, excellent melanin formation inhibiting effect and skin color brightness recovery effect, and also had good results in practical tests.

Examples 9-16. Comparative Examples 5 to 8 (Skin Cream) Similarly to [Example], various Examples with the following composition,
Preparation of skin cream of comparative example and various tests (2) Preparation method Among the components (A), oil-soluble ones are mixed in the (B) component, water-soluble ones are mixed in the (C) component, (B) Ingredients and (
C) Uniformly add and melt each component and bring the temperature to 80°C. Next, inject (C) component into (B) component and stir rR.
After mixing, the temperature was raised to 3°C while stirring. It shows good results in all cases and has an excellent whitening effect;
Well, it was obvious.

Examples 17-24. Comparative Examples 9 to 12 (Emulsions) In the same manner as in Example 1, emulsions of various Examples and Comparative Examples were prepared with the following compositions and the present test was carried out. The results are shown in Table 5.

Composition (2' Self-preparation method) Of the components (A), the oil-soluble ones are in the (B) component, and the water-soluble ones are in the (C) component. Each component is heated and dissolved uniformly to bring the temperature to 80°C.Next, the (B) component and (C) component are mixed by pressure, and the temperature is increased to 3°C while stirring. As shown, in contrast to Comparative Examples 9 to 12, Examples 17 to 24, which are whitening cosmetics of the present invention, all showed good results in the poetry test, and it is clear that they have excellent whitening effects. Ta.

(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 (1)

[Claims] (1) A whitening cosmetic characterized by containing tocopherol-L-ascorbic acid-dicarboxylic acid diester 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. ▼ R_3 is CH_2, O, CO, ((CH_2)_p-
CH=CH)_q, CHNH_2, ((CH_2)_r
-(CHCH_3)_s)_t, ((CH_2)_u-
CHOH)_v, x and y are 0 to 10
The integers p, q, r, s, t, u, and v represent integers of 0 to 4, and R_4 and R_5 represent H or CH_3. )(
2) A whitening cosmetic containing tocopherol-5,6-O-isopropylidene-L-ascorbic acid-dicarboxylic acid diester 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). are the same)