JPS607961B2 - fair skin cosmetics - Google Patents

Description

[Detailed description of the invention] The present invention relates to a novel whitening cosmetic.

More specifically, the skin whitening effect and sun protection effect of containing an esterified product of kojic acid represented by the general formula (1); (wherein R is a saturated or unsaturated aliphatic hydrocarbon group) as an active ingredient. Regarding the great whitening cosmetics.

It is common for women to want to have fair and beautiful skin, and traditionally, hydrogen peroxide, zinc peroxide, magnesium peroxide,
Cosmetics containing peroxides such as sodium peroxide, zinc perborate, magnesium perborate, or sodium perborate have been widely used.

However, the above-mentioned peroxides have problems in terms of storage stability, physical or chemical stability, or incorporation into cosmetics, and their whitening effect is also insufficient. In recent years, cosmetics containing vitamin C, cystisoline, colloidal sulfur, etc. have been developed and used, but it is said that these products still have satisfactory shelf life, stability, and whitening effects. It's tough. However, the present inventors have conducted various studies to find a skin whitening agent that does not have any unfavorable side effects on the human body and has excellent skin whitening and sun protection effects. The esterified product of kojic acid inhibits the activity of tyrosinase present in the human skin, exhibiting a remarkable melanin production inhibiting effect, and exhibiting excellent whitening and sun protection effects, as well as being effective against pH, light, heat, etc. In addition, the esterified product is highly oil-soluble and easily dissolves in the oil layer of creams, etc., making it difficult to absorb into the skin. The present invention was completed based on the new discovery that the properties of the present invention are extremely good.

The esterified product of kojic acid represented by the general formula (1), which is incorporated as an active ingredient in the fairing cosmetic composition of the present invention, is subjected to an esterification reaction between kojic acid and an aliphatic carboxylic acid in the presence of a catalyst such as zinc chloride. It can be easily obtained by

The kojic acid used in the present invention includes pure kojic acid or those of the genus Asbergillus, Benicillium, Escalychia, Acetobacter, and Gluconobacter.
It is a product obtained by extracting and crystallizing kojic acid from a fermentation liquid containing kojic acid as its main component, which is obtained by culturing a strain of a genus selected from a group consisting of genus that has a kojic acid production facility. It will be done.

Here, examples of strains of the genus Asbergillus having the ability to produce kojic acid include Asbergillus al/us, Asbergillus straindus, Asbergillus oryzae, Asbergillus nidulans, Asbergillus rashiticus, and Asbergillus. Strains such as Awamori, Asbergillus tamari, Asbergillus niebieus, Asbergillus fura/su, Asbergillus wench, Asbergillus glaucus, Asbergillus clavaitus, Asbergillus fumigatus, Asbergillus digitus, etc. Examples of strains of the genus Benicillium include strains such as Benicillium dale; examples of strains of the genus Escalychia include, for example, Escalychia.
strains such as Acetobacter coli, and Acetobacter strains such as Acetobacter aceti and Acetobacter aceti.
Bacterial strains such as Gluconicus and Acetobacter xylinum can be suitably employed, and strains of the genus Gluconobacter such as Gluconobacter rosius and Gluconobacter gluconicus can be suitably employed. The culture medium composition of these strains usually contains about 2 to 3 carbon sources such as sucrose, fructose, glucose, starch, maltose, glycerin, mannite, rhamnose, xylose, gluconic acid, arabinose, dihydroxyacetone, inosyte, lactose, and ethanol. 15% (wt%, the same applies hereinafter), about 0.1 to 1% nitrogen sources such as ammonia sulfate, polybeptone, sodium nitrate, baker's yeast extract, brewer's yeast extract, etc.
Magnesium sources such as magnesium sulfate are about 0.01~
0.05% phosphorus and potassium sources such as monohydrogen phosphate and dihydrogen phosphate, 0.01 to 0.1%, and other sources such as ferric sulfate, ferric chloride, sodium chloride, calcium chloride, etc. About 0.001 to 0.005% of inorganic salts may be used.

Therefore, fermented liquids with different compositions of ingredients can be obtained depending on the type of bacterial strain used and the composition of its medium. Kojic acid is obtained by extracting and crystallizing kojic acid from a kojic acid-containing fermentation liquor.These kojic acids themselves have strong tyrosinase activity inhibiting power, but when the kojic acid is converted into an aliphatic carboxylic acid, By reacting to form an ester, its ability to inhibit tyrosinase activity is further increased, and its stability against light and pH is increased, resulting in extremely good storage stability. Furthermore, its oil solubility is increased, and it is incorporated into creams, etc. It has excellent skin whitening and sun protection effects by easily dissolving into the oil layer and increasing skin absorption.

The aliphatic carboxylic acids used in the present invention include saturated aliphatic carboxylic acids, unsaturated aliphatic carboxylic acids,
etc.

Saturated aliphatic carboxylic acids include, for example, acetic acid, propionic acid, n-green acid, iso-valeric acid, methylethyl acetic acid, trimethylacetic acid, caproic acid, enanthic acid, caprylic acid, belargonic acid, capric acid, undecylic acid, lauric acid. Acids such as tridecylic acid, myristic acid, bentadecylic acid, palmitic acid, margaric acid, stearic acid, nonderelic acid, arachidic acid or lignoceric acid are used.
It is preferable to use the above saturated aliphatic carboxylic acids, especially C,4-2o saturated aliphatic carboxylic acids.

Furthermore, C2. Although the use of the larger aliphatic carboxylic acids is not particularly limited, they are extremely difficult to obtain and therefore are not preferred in terms of production costs. In addition to these saturated aliphatic carboxylic acids, unsaturated aliphatic carboxylic acids such as linoleic acid, linolenic acid, maleic acid, fumaric acid, olefinic acid and arachidonic acid can be used without any particular limitation.

The fair skin cosmetic of the present invention contains an esterified product as described above in an appropriate cosmetic base, and the content of the esterified product is usually about 0.01 to 10%, particularly 1 to 5%. A range of degrees will be adopted.

However, within this range, satisfactorily whitening and sun protection effects can be achieved; however, when the content is greater than 10%, there is no commensurate benefit; on the other hand, the content is less than 0.1%. This is because there are some concerns about the whitening effect and sun protection effect when using it. As described above, the skin-lightening cosmetic of the present invention can overcome the drawbacks of conventional products by containing an esterified product of kojic acid as a whitening agent, and is not limited by the cosmetic base material used. It's not a thing.

Therefore, in the present invention, various basic cosmetic base materials that have been conventionally widely used as cosmetic base materials, such as various alcohols, animal and vegetable fats, surfactants, pectin, carboxymethyl cellulose, alginates, and stabilizers, Colorants, fragrances, and other ingredients may be appropriately blended and, if necessary, heated and melted or melted, and the like can be used as is. Next, the esterified product used in the present invention as a skin whitening agent and sunscreen will be described in detail with reference to reference examples and examples.

Reference example 1 (Kojic acid obtained by culturing Asbergillus albus having the ability to produce kojic acid) Sucrose 5 as a medium
%, potassium dihydrogen phosphate 0.03%, magnesium sulfate 0
．． 0.01%, calcium chloride 0.01%, ferric chloride 0.01%, calcium chloride 0.01%, ferric chloride 0.
001%, sodium chloride 0.001%, beptone 0.001%, sodium chloride 0.001%, beptone 0.
Using a 5% aqueous solution adjusted to pH 4, the same volume was filled into a flat flask, and the pressure was 15 kg/mm.
After high-pressure sterilization for a minute, add Asbergillus to this medium.
Albus (obtained from Utsunomiya University), 2
Static culture was performed at 8q○ for 10 days.

After culturing, the bacterial lid was removed and the culture solution was filtered to obtain kojic acid 2.
A fermentation liquid containing 5% was obtained. 1000' of this fermented liquid
Add 400' of 5% cupric acetate to
150 minutes of precipitate was obtained after 0 minutes from the powder.

This precipitate was suspended in approximately 1" volume of 1,500 ml of water,
Next, hydrogen sulfide is sufficiently passed through to precipitate cupric sulfide.
This was removed by furnace filtration, and the obtained furnace liquid was concentrated under reduced pressure at 50q0 to obtain a concentrated liquid of 500ml. This concentrated solution was extracted three times with 2,000 ml of ethyl acetate, and the resulting ethyl acetate extract was concentrated under reduced pressure at 5,000 ml of ethyl acetate to obtain 25 ml of crude crystallized kojic acid. Add this to 2000 ethyl acetate [
It was recrystallized to obtain 20 days of kojic acid. Reference Example 2 22.8 mm (0.1 mol) of myristic acid and 4.8 mm of zinc chloride.
Dissolve 1 night (0.03 mol) while worshiping, 1403
Heated at ○ for 30 minutes.

Next, 4.3 moles (0.03 mol) of pure kojic acid (manufactured by Sigma) was gradually added to this solution under the supervision of a ``further 14 mol.''
000 for 2. The song was called Heated Fly Azusa. After standing overnight at room temperature, the mixture was washed with 300 g of water, extracted three times with 200 g of ether, and the ether extract was neutralized with sodium bicarbonate.

The extract was concentrated under reduced pressure at 30 oo to obtain a crude crystal product 13.
．． It took 5 evenings. This product was recrystallized with 300M ether to obtain an esterified product of kojic acid and myristic acid. Reference Example 3 Stearic acid 2 was used in place of myristic acid used in Reference Example 2.
An esterified product of kojic acid and stearic acid 13 was obtained in the same manner as in Reference Example 2, except that 8.5% (0.1 mol) was used and the kojic acid obtained in Reference Example 1 was used as kojic acid. .

Reference Example 4 Caprylic acid 14 was used instead of myristic acid used in Reference Example 2.
．． A esterified product of kojic acid and caprylic acid, 7.5 mole, was obtained in the same manner as in Reference Example 2, except that 4 mole (0.1 mole) was used.

Reference Example 5 An esterified product of kojic acid and oleic acid was obtained in the same manner as in Reference Example 3 except that oleic acid was used in place of the stearic acid used in Reference Example 3.

The melting points and ferric chloride test results of each acyl derivative of kojic acid thus obtained are shown in Table 1 together with the test results for pure kojic acid.

Table 1 Each sample is a 0.5 mol/10% ethanol solution.

Examples 1 to 4 The esterified product of kojic acid and myristic acid obtained in Reference Example 2 was dissolved in ethanol to a concentration of 1.
A 0% IJ Niment agent (Example 1) was prepared.

In the same manner, each liniment agent (Examples 2 to 4) was prepared using each esterified product obtained in Reference Examples 3 to 5. In order to examine the ability of these liniment agents to inhibit tyrosinase activity, we placed an L-tyrosine solution (0.3/9/
mucklevaine's buffer (pH 6.8)
) was added to 1 and 0.9' of Niment agent obtained in Example 1, and incubated in a thermostatic water bath at 37°C for 10 minutes.
0.1 (on the desk) was added, the mixture was thoroughly shaken, and the absorbance of each of the 475 Buddhas was measured over time by immediately setting it on a spectrophotometer.

On the other hand, as a blank test, similar absorbance measurements were performed using water instead of the liniment agent. In the same manner, the liniment agents of Examples 2 to 4 were examined for their ability to inhibit tyrosinase activity.

Comparative Example 1 A liniment agent was prepared using pure kojic acid in the same manner as in Examples 1 to 4, and its ability to inhibit tyrosinase activity was examined.

FIG. 1 is a graph showing the measurement results of Examples 1 to 4 and Comparative Example 1. From this graph, it can be seen that the liniment agents of Examples 1 to 4 all have more significant tyrosinase activity than the liniment agents made of kojic acid. It can be seen that it has an inhibitory power.

Examples 5 to 8 Each of the esterified compounds obtained in Reference Examples 2 to 5 was dissolved in a 50% ethanol solution of 100% each to 1%
A liniment preparation was prepared.

Add sodium hydroxide to this to adjust the pH to 10.0.
The degree of coloration of each rice cake was measured over time using a spectrophotometer (420 Hada Buddha) while maintaining the temperature at 50°C.

Comparative Example 2 A liniment agent was prepared in the same manner as in Examples 5 to 8 using pure kojic acid, and changes in the degree of coloration were examined under the same conditions as in Examples 5 to 8.

Figure 2 is a graph showing the results of these tests, and it can be seen from this graph that all the liniment agents of Examples 5 to 8 have better stability against pH and heat than the liniment agents made of kojic acid. Recognize.

Further, each of these liniment agents was irradiated with ultraviolet light of 270 degrees Celsius, and the degree of coloration of each was measured over time using a spectrophotometer (420 degrees Celsius).

Further, pure kojic acid obtained in Comparative Example 2 and Nimento agent were also tested in the same manner. FIG. 3 is a graph showing these test results. From this graph, Example 5
All of the liniment agents No. 8 to 8 had better stability against light than the liniment agent made of kojic acid.

Example 9 A vanishing cream was prepared using the esterified product obtained in Reference Example 2 at the blending ratio shown in Table 2.

Table 2 This vanishing cream was applied evenly to the arms of 40 panelists, and the applied surface was exposed to ultraviolet rays of 270 degrees and 340 degrees of ultraviolet rays at levels 1, 2 and D (minimum amount of erythema produced). Although irradiated with ultraviolet rays at the same time, no erythema occurred on any of the panels under any conditions.

Example 10 A vanishing cream (test drug S) was prepared using the esterified product obtained in Reference Example 3 at the blending ratio shown in Table 3.

Table 3 For comparison, a vanishing cream (placebo) was prepared by replacing the esterified product obtained in Reference Example 3 with the same amount of purified water among the compositions shown in Table 3.

Two 2×2 skin sections were set up on the inner side of the upper arms of 30 panelists, and were designated as A section and B section.

Both compartments were then irradiated for 5 minutes with two FL2 eaves/BLB lamps and two FL2 eaves/E30 lamps from a distance of 10 celsius. Immediately after irradiation, test drug S was applied to section A and placebo was applied to section B three times a day for 7 days, and the degree of improvement in pigmentation was examined after 7 days.

The results are shown in Table 4. The degree of improvement in pigmentation was determined by visually comparing the degree of pigmentation in section A (applied with test drug S) and section B (applied with placebo), and the degree of improvement in section A relative to section B was determined.

Table 4 As is clear from Table 4, the esterified product of the present invention can significantly suppress pigmentation in the human body compared to the placebo.

As is clear from the above examples, the skin-whitening cosmetic of the present invention uses the esterified kojic acid represented by the above general formula (1) as its active ingredient, and has an extremely excellent tyrosinase activity inhibiting ability. The esterified product has excellent stability against light, pH, and heat, does not cause any side effects on the human body, and has extremely great whitening and sun protection effects.

[Brief explanation of the drawing]

Figure 1 is a graph showing the relationship between the degree of coloring and time to show the tyrosinase activity inhibiting power of each liniment agent obtained in Examples 1 to 4, and Figures 2 and 3 are graphs obtained in Examples 5 to 8. 1 is a graph showing the degree of coloration versus time to show the stability against pH and heat of each liniment agent; and a graph showing the relationship between the degree of coloration and time to show the stability against light. Figure 1 Figure 2 Figure 3

Claims (1)

[Claims] 1 General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R is a saturated or unsaturated aliphatic hydrocarbon group) A fair-skinned cosmetic characterized by containing it as an ingredient. 2. The fair-skinned cosmetic according to claim 1, wherein the content of the esterified product is 0.01 to 10% by weight. 3. The fair-skinned cosmetic according to claim 1, wherein R is a saturated aliphatic hydrocarbon group of C_1 or more. 4. The fair skin cosmetic according to claim 3, wherein the R is a saturated aliphatic hydrocarbon group of C_1_3 to C_1_9.