JPH01143813A - Melanization inhibitory drug for external use - Google Patents

Abstract

PURPOSE:To obtain an excellent melanization inhibitory drug for external use, containing an O-acylmannosamine, O-acylgalactosamine and/or salts thereof as an active ingredient and capable of remarkably inhibiting melanization with hardly and cytotoxicity. CONSTITUTION:A melanization inhibitory drug for external use, obtained by blending an O-acylmannosamine, O-acylgalactosamine, preferably an O-monoacyl or O-tetraacyl derivative of mannosamine or galactosamine, in which the acyl group is preferably an acyl group derived from 2-21C fatty acids and salts thereof, e.g., hydrochloride, sulfate, nitrate or phosphate, preferably hydrochloride as an active ingredient in an amount of 0.001-20wt.%, preferably 0.01-10wt.% based on the total weight of the drug for external use with other ingredients and having the above-mentioned effects effective in preventing pigmentation, such chloasma, and in whitening of liver-spot, ephelis, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to the treatment of pigmentation such as melasma using O-acylmannosamine and O-acylgalactosamine as active ingredients;
The present invention relates to an external melanin production suppressing agent for prevention and whitening of human skin.

[Conventional technology]

Cosmetics containing peroxides such as hydrogen peroxide and zinc peroxide have been used since ancient times to remove spots such as age spots and freckles that appear on the skin.

However, since these peroxides are extremely unstable substances, they have problems in storage stability and incorporation into cosmetic bases, and furthermore, they do not have sufficient skin-whitening effects. Furthermore, cosmetics containing vitamin C, cysteine, colloidal sulfur, etc. have come to be used for the purpose of fairing the skin, but their effects are still not fully satisfactory.

Furthermore, fair skin cosmetics using kojic acid
No. 569), ointment for suppressing melanin production using kojic acid (Japanese Patent Publication No. 61-10447), whitening cosmetics containing kojic acid derivatives (Japanese Patent Publication No. 61-60801, Japanese Patent Publication No. 61-60802) Publication, JP-A-56-7
No. 9616, etc.) are disclosed. In addition, fair skin cosmetics containing quercetin and flavonol compounds (JP-A-55-92305, JP-A-55-11141)
Publication No. 0, JP-A-55-111411, JP-A-5
5-143908, etc.) are disclosed.

Furthermore, skin whitening cosmetics containing placenta extract (Japanese Patent Publication No. 4B-30370) and melanin production inhibiting external preparations containing vitamin E and kojic acid (Japanese Patent Publication No. 62/1989)
-178506), it has also been disclosed that vitamin tantan is dissolved in water and used for whitening cosmetics (Japanese Patent Laid-Open No. 56-7
5421).

On the other hand, cosmetics containing amino sugars, N-acetylamino sugars, and N-alkylamino sugar sugar alcohols have a smooth feeling on the skin, a moisturizing feeling, a softening effect, and a skin revitalizing effect (Japanese Patent Application Laid-Open No. 1983-1989-1). Publication No. 13708, JP-A-59-2
12419), fair skin cosmetics containing glucosamine and acylated glucosamine derivatives (Japanese Patent Laid-Open No. 62-363)
No. 06) is disclosed.

[Problem that the invention seeks to solve]

In the conventional technology, among the ingredients used in skin-lightening cosmetics,
The action of peroxide is to directly reduce and bleach pigments such as melanin produced on the skin, and excessive use could bleach the skin's original color, causing the skin to turn white.

In addition, kojic acid, flavonol, vitamin E, etc. directly inhibit the production of melanin in cells, and are useful drugs that produce a skin-whitening effect, but there are drawbacks to their formulation methods.

[Means for solving problems]

The present inventor conducted research on the melanin production suppressive effects of O-acylmannosamine and O-acylgalactosamine, and in particular investigated cell access using 816 cells derived from mouse melanoma. discovered the surprising fact that 0-acyl derivatives of mannosamine and galactosamine have a marked effect on inhibiting melanin production in 816 cells, despite not exhibiting any melanin production inhibiting effect, and have used this as a treatment for pigmentation disorders such as melasma. The present invention has also been completed, which can be used for whitening age spots, freckles, etc.

The present invention is an external preparation for suppressing melanin production, which contains one or more of O-acylmannosamine, O-acylgalactosamine, and salts thereof as an active ingredient.

The active ingredients of the present invention, 0-acylmannosamine and 0-acylgalactosamine, are one of mannosamine and galactosamine.
~4 hydroxyl groups are acylated with 1 to 4 acyl groups, and the acyl group is preferably an acyl group derived from a fatty acid having 2 to 21 carbon atoms.

Examples of salts include hydrochloride, sulfate, nitrate, phosphate, etc., with hydrochloride being preferred.

0-acylmannosamines include 1-0-acetylmannosamine, 1-0-propylmannosamine, 6-0-
Low monoacylmannosamines such as octanoylmannosamine and 6-0-octadecanoylmannosamine, 1°6
-0-diacylmannosamine such as di-0-acetylmannosamine, 1,3.6-tri-loacetylmannosamine, 0-triazilmanosamine such as 1.4.6~ tri-0-acetylmannosamine, etc. O-tetraacylmannosamines such as nosamine, O-tetraacetylmannosamine, and O-tetrapropionylmannosamine are included.

Examples of O-acylgalactosamines include lo-monoacylgalactosamines such as 1-loacetylgalactosamine, 1-lopropionylgalactosamine, 6-0-octanoylgalactosamine, and 6-looctazocanoylgalactosamine; 0-diacylmannosamine such as acetylgalactosamine, 1.3.6-tri〇-acetylgalactosamine, 1,4.6-) di-
Included are 0-triazylgalactosamines such as 0-acetylgalactosamine, and 0-tetraacylgalactosamines such as O-tetrapropionylgalactosamine.

Suitable examples include O of mannosamine and galactosamine.
-monoacyl and O-tetraacyl derivatives.

The external preparation of the present invention contains one or more of the active ingredients O-acylmannosamine and O-acylgalactosamine in emulsions, lotions, liniments, ointments, lotions, creams, milky lotions, etc. It can be obtained by a conventional formulation method using bases and auxiliary agents commonly used in the preparation of formulations such as cosmetics.

The content of the active ingredient of the present invention is O,
O01-20% (by weight), preferably 0, O1-10% (by weight)
heavy weight).

Next, a test example showing the inhibition of melanin production by the melanin production inhibiting external preparation of the present invention will be given.

Test Example 1 Mouse melanoma-derived 816 cells (hereinafter abbreviated as B16 cells) 1-0-acetylmannosamine hydrochloride, 1
- Lopropionylgalactosamine, rhotetraacetylmannosamine, and O-tetraacetylgalactosamine were added to the medium at various concentrations, and the cells were cultured at 37°C for 5 days, and the number of cells was measured. Afterwards, the degree of blackness (degree of melanin production) of each cell pellet was observed with the naked eye.

1; N-acetyl-D-glucosamine as a control;
Glucosamine (a known melanin production inhibitor) and (, (
The same test was conducted by adding N-acetyl-D-mannosamine and N-acetyl-rogalactosamine (compounds similar to the active ingredient of the present invention) at similar concentrations. In addition, as a control, the active ingredients were not added.
A similar test was conducted.

The test results were as shown in Table 1 below.

(Margin below) Table 1 As is clear from the above test results, 1-0-acetylmannosamine hydrochloride and 1-lopropionylgalactosamine almost completely whitened the cells at 5 mg/m/Q. 0-tetraacetylmannosamine and O-tetraacetylgalactosamine are particularly effective <0, O2mg/
Me almost completely whitened the skin, and the whitening effect was approximately 50 times greater than that of glucosamine. On the other hand, none of the N-acyl derivatives turned white. In addition, when glucosamine is added, cell growth inhibition is observed compared to cell whitening, but the active ingredient of the present invention has a weaker cell growth effect than glucosamine, especially O-tetraacetylmannosamine, O-tetra Acetylgalactosamine shows almost complete whitening at 0. No growth inhibition was observed in the absence of lomg/me addition. Thus, it can be seen that the active ingredient of the present invention has no cytotoxicity and has an extremely excellent melanin production inhibiting effect.

Next, examples of the present invention will be described.

〔Example〕

Example 1 (Emulsion) Weight part A, polyoxyethylene glycol monostearate (
40E, 0. ) 2, O0 self-emulsifying glycerin monostearate 5, O0 stearic acid 5, O0 behenyl alcohol 1, O0 liquid paraffin
1, O0 trioctanoic acid glycerin 1O1
00 Preservatives Appropriate amount of fragrance
Trace amount B, 1.3-butylene glycol 5, O00-tetraacetylmannosamine 0.50 purified water The remaining components belonging to A are dissolved by heating (oil phase).

Separately, the components belonging to the above are dissolved by heating (aqueous phase).

The aqueous phase was added to the oil phase, stirred, emulsified, and then cooled to obtain an emulsion.

Example 2 (Lotion) Part by weight Polyoxyethylene hydrogenated castor oil 1, O0 (60E,
0. ) Ethanol 15, O0 Citric acid 0.10 Sodium citrate 0.30 1.3-Butylene glycol
4, O00-tetraacetylgalactosamine
0, O5 night protectant, appropriate amount of fragrance
micro purified water
Stir, mix, and dissolve the remaining ingredients uniformly.
A lotion was obtained.

Example 3 (emulsion) Weight part A, polyoxyethylene behenyl ether (20B,
O. ) 0.50 Tetraoleic acid polyoxyethylene sorbitol (60B, mouth,) 1, O
0 Lipophilic glycerin monostearate 1, O0 Stearic acid 0.50 Behenyl alcohol 0.50 Avocado oil
1, O0 preservative appropriate amount fragrance trace amount B, 1.3-butylene glycol 5,00 carboxyvinyl polymer 0.101-low propionyl galactosamine 0. 1O purified water Heat and dissolve the components belonging to Residue A (oil phase). Separately, components belonging to B are dissolved by heating (aqueous phase). The aqueous phase was added to the oil phase, stirred and emulsified, and then cooled to obtain a milky lotion.

Example 4 (Ointment) Weight part A, polyoxyethylene sorbicun monostearate (
60B, O. ) 1, O0 polyoxyethylene sorbitate tetraoleate (60B,
O. ) 1.50 Self-emulsifying glycerin monostearate 1.50 White beeswax 2, O0 paraffin 2, O0 stearic acid
3. O0 behenyl alcohol
3, O0 liquid paraffin 5, O
0 preservatives, appropriate amount of fragrance
Trace amount B, 1,3-butylene glycol 5, O0 citric acid
0.301-〇-acetylmannosamine hydrochloride
1. Heat and dissolve the components belonging to O0 purified water (oil phase). Separately, the components belonging to the above are dissolved by heating (aqueous phase). The aqueous phase was added to the oil phase, emulsified by stirring, and then cooled to obtain an ointment.

〔Effect of the invention〕

As described above, the present invention is a useful invention that provides an extremely excellent melanin production-inhibiting topical agent that has almost no cytotoxicity and significantly inhibits melanin production.

Claims (1)

[Claims] 1. An external preparation for suppressing melanin production, which contains one or more of O-acylmannosamine, O-acylgalactosamine, and salts thereof as an active ingredient.