KR0149995B1 - Topical agent for inhibiting melanin production - Google Patents

Abstract

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Description

External preparation to inhibit melanin production

The present invention is formulated into external bases applied to skin such as cosmetics and ointments, inhibits the production of the most basic enzyme tyrosinase of the melanin-generating system, and prevents whitening, sunburn and blackening. It relates to a melanin production-inhibiting external preparation having a pigmentation prevention effect such as i).

Melanin is present in the skin, and its production is caused by the action of tyrosinase in the pigment cells in the skin tissue, whereby tyrosine is converted into dopa, followed by dopa quinone, and 5,6-dihydrooxyindole produces melanin. It is supposed to. In addition, excessive production of melanin amounts causes pathological defects such as cosmetic defects such as blemishes and freckles, and pigmentation such as liver spots on the skin surface.

For the melanin produced on the surface of the skin, a bleaching agent containing a bleaching agent such as hydroquinone, hydroquinone monobenzyl ether, etc. is used, but these have a strong color whitening effect, degeneration of pigment cells, and lethality. Impaired physiological function of, and it is undesirable because there is a risk of causing plaque-like or reticulum as a side effect.

So, focusing on the mechanism of melanin production and searching for a variety of substances that have an effect of inhibiting the activity of tyrosinase, the fact that koji acid and koji acid derivatives have this remarkable effect, and the color cosmetics using koji acid , External preparations are known. (Japanese Unexamined Patent Application Publication No. 61-10447) Moreover, color cosmetics using koji acid derivatives are known. (For example, JP-A-56-7710, JP-A-56-79616, JP-A-59-79616)

In the prior art, external preparations including hydroquinone and hydroquinone derivatives, which are used as decolorants, may cause plaque or reticulated alum as side effects, which is not preferable. In addition, external preparations containing tyrosinase inhibitors such as koji acid and koji acid derivatives are excellent as melanin production-inhibiting external preparations that do not involve side effects such as alum, which are found in hydroquinone, hydroquinone derivatives, etc., but the activity of tyrosinase produced once And inhibit action, not fundamentally inhibit melanin production.

This disease aims at providing the external agent which has a more effective, fundamentally melanin production inhibitory effect.

The present inventors do not first inhibit the activity of tyrosinase that is directly involved in melanogenesis in the melanin production system, but search for a substance that inhibits the production of tyrosinase and discover that acetic acids, lactic acid, and pyruvic acid have this action. And an enzyme production inhibitor containing these substances as active ingredients were filed as Japanese Patent Application No. 63-134481.

In addition, propionic acids, butyric acids and valeric acid were found to have this action, and an enzyme production inhibitor containing these substances as an active ingredient was invented and filed as Japanese Patent Application No. 63-134482.

Based on this knowledge, the present inventors completed the present invention by finding an external agent that completely inhibits melanin production by synergistic action of substances by using a tyrosinase production inhibitor and a tyrosinase activity inhibitor.

The present invention is a melanin production-inhibiting external preparation comprising one or two or more acids selected from koji acid or koji acid derivatives and acetic acid, lactic acid, pyruvic acid, propionic acid, butyric acid and valeric acid.

Kojisan, one of the active ingredients of the present invention, is 5-hydrooxy-2-hydrooxymethyl-r-pyron produced by various carbohydrate compounds by Kojisan producing strains belonging to the genus Aspergillus, Penicillium, and the like.

In addition, the koji acid derivatives are mono fatty acid esters of koji acid, such as koji acid mono-melmitate, koji acid monobutylate, koji acid monocaprylate, and koji acid monostearate (see Japanese Patent Application Laid-Open No. 56-77272). ), Koji acid difatty acid ester, such as koji acid dipalmitate, koji acid dioleate, koji acid dibutylate, koji acid distelalate (see Japanese Patent Application Laid-Open No. 56-7776), Koji monoshinnamo Eight, Koji-mono monobenzoate (refer Unexamined-Japanese-Patent No. 59-33207), etc. are included.

Acids, which are other active ingredients of the present invention, include salts such as acetic acid, L-lactic acid, DL-lactic acid, lactic acid, propionic acid, ortho butyric acid, isobutyric acid, ortho valeric acid, iso valeric acid and alkali metal salts of these acids, alkaline earth metal salts, and the like. Esters of these acids, acid amides, and the like.

The external preparation of the present invention can be obtained by combining one or two or more types of koji acid or koji acid derivatives with acetic acid, lactic acid, pyruvic acid, propionic acid, butyric acid, valeric acid and the like by a conventional method and a conventional method. Can be.

The external preparation of the present invention may be used for the purpose of preventing melanin deposition on the skin by inhibiting melanin production, and various cosmetics such as creams, lotions, packs, powders, cosmetics, emulsions, lotions, coating agents, ointments, etc. Formulated in an external form of eggplant, bases, excipients, stabilizers, pigments, fragrances, ultraviolet absorbers, antioxidants, preservatives, metal containment agents, and the like, which are commonly used in the formulations, may be formulated.

The blending ratio of koji acid, koji acid derivatives and acids is usually 1: 0.1 to 1: 100 by weight ratio, preferably 1: 1 to 1:10, which can sufficiently bring about a synergistic effect.

The compounding ratio of the active ingredient of the present invention is 0.1 to 3% (weight) for koji acid or koji acid derivatives, and 0.1 to 30% (weight) for acids, with respect to the entire external preparation.

Koji acid, koji acid derivatives, acetic acid, lactic acid, pyruvic acid, propionic acid, butyric acid and valeric acid are all low toxicity to the human body, and there is no problem even if they are used in combination.

The external preparation of the present invention strongly inhibits the production of tyrosinase itself by the action of acetic acid, lactic acid, pyruvic acid, propionic acid, butyric acid and valeric acid, and also significantly inhibits the activity of tyrosinase by the action of koji acid and koji acid derivatives. It has a very good melanin production inhibitory effect by the synergism of both inhibitors.

Next, the present invention will be described in more detail with reference to Examples of the present invention and test examples showing the effects thereof.

EXAMPLE

Example 1 (cream)

[Manufacturing method]

A. Warm and dissolve 1 to 7.

B. Warm and dissolve 8-12.

C. B is added to A, emulsified, stirred and cooled.

D. Cool C, fill it in a container, and make it as a product after inspection.

[Usage and Dose]

Apply an appropriate amount to the face.

Example 2 (latex)

[Manufacturing method]

A. Warm and dissolve 1 to 8.

B. Warm and dissolve 9-14.

C. B is added to A, emulsified, stirred and cooled.

D. Cool C, fill it to a container, and make it as a product after inspection.

[Usage and Dose]

Apply an appropriate amount to the face.

Example 3 (lotion agent)

[Manufacturing method]

A. Stir and dissolve 1-10 uniformly.

B. Fill A into the container and inspect the product.

[Usage and Dose]

Apply an appropriate amount to the face.

Example 4 (cream pack)

[Manufacturing method]

A. Warm and dissolve 1 to 7.

B. Warm and dissolve 8-12.

C. B is added to A, emulsified, stirred and cooled.

D. Cool C, fill it to a container, and make it as a product after inspection.

[Usage and Dose]

Apply an appropriate amount to the face.

Example 5 (ointment)

[Manufacturing method]

A. Warm and dissolve 1 to 11.

B. Warm and dissolve 12-15.

C. B is added to A, emulsified, stirred and cooled.

D. Cool C, fill it to a container, and make it as a product after inspection.

[Usage and Dose]

Apply an appropriate amount to the face.

Example 6 (emulsion)

[Manufacturing method]

A. Warm and dissolve 1 to 8.

B. Heat and dissolve a portion of 9-14.

C. B is added to A, emulsified, stirred and cooled.

D. Cool C, fill it to a container, and make it as a product after inspection.

[Usage and Dose]

Apply an appropriate amount to the face.

[Test Methods]

The melanin production inhibitory effect in a pigment cell is measured according to the method described in "Cancer Reserch", Vol. 42, No. 1194 to 2002 (1982).

That is, 4 × 10 mouse melanoma-derived cells B-16 are suspended in 10 ml of Eagle MEN medium containing 10v / v% fetal calf serum and cultured at 37 ° C. in 25 cm² cultured ileus in the presence of 5v / v% CO 2. The culture solution is exchanged in a medium containing a sample for tyrosinase production inhibition test on days 0 and 3 and cultured for 5 days. Cells are washed with phosphate buffer (PH 7.2) containing 0.8 w / v% saline, then exfoliated using a solution containing trypsin and EDTA, and the cells are recovered by filtration.

After the cells collected on the filter paper are dried, the reflected light at 500 nm is measured by a densitometer, and the total amount of melanin is determined by the reflected absorbance (blackness).

By this method, it is determined that the treatment region when the absorbance of the treatment region is reduced to 80% or less of the absorbance of the control standard exhibits melanin production inhibitory action.

Whitening Activity of Koji Acid and Koji Acid Fluid in Cultured Pigment Cells

(Note) + means that there is a melanin production inhibitory action,-means that does not show an inhibitory action. (Hereafter, the same applies to Tables 2 to 6.)

Color Whitening Effect of Organic Acids in Cultured Pigment Cells

Synergistic Whitening by Combination of Organic Acid, Koji Acid and Koji Acid Derivative in Cultured Pigment Cells

50 men and women (25 males, 25 females, 25 males, 25 males, average age males, ages 21-55) randomly selected for the melanin production inhibitory external preparations of Examples 1, 2, 3 and 5 Females were aged 42.3 months and questionnaire was examined for safety and effectiveness.

The results are shown in Table 7.

(Note) The numbers in the table indicate the number of people.

As is apparent from this result, the melanogenesis inhibitor of the present invention can be safely used without side effects, and has shown a very good therapeutic effect against pigmentation.

The melanin production-inhibiting external preparation of the present invention inhibits the production of tyrosinase itself, which is directly involved in melanogenesis by acetic acids, lactic acid, pyruvic acid, propionic acid, butyric acid and valeric acid, and is also used for koji acid and koji acid derivatives. Is a topical agent that significantly inhibits melanin production by the action of inhibiting the activity of tyrosinase, and by applying this external agent, melanin caused by blemishes, freckles, and liver caused by skin deposition of melanin, which was previously difficult to prevent and treat. It is a very useful invention that prevents deposition and makes treatment possible.

Claims (1)

An external preparation for inhibiting melanin production, comprising kojic acid or kojic acid derivatives and one or two or more acids selected from acetic acids, lactic acid, pyruvic acid, propionic acid, butyric acid and valeric acid.