JPH0581566B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to fair skin cosmetics. [Prior Art] Generally, when the skin is irradiated with ultraviolet rays from sunlight, melanin is significantly produced in the pigment cell melanocytes in the skin, and the skin tends to turn black. Ascorbic acids (Japanese Unexamined Patent Application Publication No. 1983-1993) are used as substances in cosmetics for the purpose of preventing skin darkening caused by sunburn and removing spots and freckles caused by melanin pigment deposition. 65007), hydrogen peroxide, glutathione (Japanese Patent Publication No. 57-134410), colloidal sulfur, hydroquinone (Japanese Patent Publication No. 59-157009), kojic acid (Japanese Patent Publication No. 1983-157009),
-7961), cinnamaldehyde (Japanese Patent Application Laid-open No. 58-55414), etc. However, ascorbic acids are easily oxidized and unstable in systems containing a lot of water such as wet products, causing discoloration and odor. This tends to be the case. Due to the characteristics of hydrogen peroxide, it is difficult to say that it is sufficient in terms of safety, storage, and stability. Glutathione and colloidal sulfuric acid give off a strange odor, so their use in fairing cosmetics is avoided. Hydroquinone is highly cytotoxic and cannot be said to be sufficient from a safety standpoint. Furthermore, in small amounts, kojic acid and cinnamaldehyde have a small effect in preventing skin darkening, and cannot be said to be sufficient for use in fair skin cosmetics. In recent years, glucosamine hydrochloride purified from crab shells, etc. has been used in culture systems for melanin-producing pigment cells (melanotic melanoma cells).
It was discovered that pigment cells can be whitened without irreversible loss of melanin production ability (Genji Imokawa, Yutaka Mishima: Intracultured Melanoma Cells)
Electron microscopic analysis of glucosamine-induced suppression of melanin production. Proc.Jap.Soc.Invest.Derm., 5:103-104,
1980). The above-mentioned effect of glucosamine hydrochloride on pigment cells is that when administered to the human body as a skin-lightening cosmetic, unlike hydroquinone, it does not irreversibly lose the melanin production ability of pigment cells, so it does not cause skin damage such as vitiligo. This suggests that there are few. However, in order for glucosamine hydrochloride to exhibit its whitening effect on pigment cells, a high concentration of glucosamine hydrochloride is required, and it is difficult to be absorbed into the body through transdermal absorption, so it cannot be used as is in skin-whitening cosmetics. Usage effect is small. [Problems to be solved by the invention] In view of the current situation, the inventors have worked diligently with the aim of providing a skin-whitening cosmetic that has a large whitening effect, is reversible, and is highly safe for the skin. As a result of research, it was discovered that acyl derivatives of glucosamine have a significantly strong skin whitening effect on pigment cells, and that this effect is reversible, leading to the completion of the present invention. [Means for solving the problem] That is, the present invention solves the following problems: (1) Equation

[Effect]

Next, the whitening effect of glucosamine derivatives, which are the active ingredients of the present invention, on melanin-producing pigment cells (melanotic melanoma cells) will be demonstrated in the following test examples. Example 1 Tetra-O-acetyl-glucosamine hydrochloride Tetra-O-propanoyl-glucosamine hydrochloride N-octanoyl-glucosamine N-acetyl-1,3,4,6-tetra-O-
Propionylglucosamine N-acetyl-1,3,4,6-tetra-O-
Butyrylglucosamine N-acetyl-1,3,4,6-tetra-O-
Acetylglucosamine N-acetyl-3,4,6-tri-O-butyrylglucosamine N-acetyl-3,4,6-tri-O-propionylglucosamine N-acetyl-3,4,6-tri-O-acetyl Glucosamine N-acetyl-1-propionylglucosamine N-butyryl-1,3,4,6-tetra-O-
Butyrylglucosamine O-β-octanoyl-glucosamine acetate N-octadecanoyl-glucosamine O-β-octadecanoyl-glucosamine hydrochloride N-montanoyl-glucosamine N-mericinoyl-glucosamine N-linolenyl-glucosamine N-elcanyl-glucosamine N-acetylglucosamine Glucosamine hydrochloride Hydroquinone Kojic acid Alcorbic acid Preparation of sample solution The test substance was dissolved in pure water to the concentration shown in Tables 1-1 and 1-2, and then placed in a safety gear cabinet with a pore size of 0.2 μm. It was filtered with a sterilization filter and used as a sample solution.

【table】

[Table] Pigment cells Pigment cells are B- cells that have been established as cultured cells.
16mouse melanotic melanoma cells were used. Test method In a safety cabinet, a shear plate (60mm
diameter), add 0.1 ml of sample solution, 0.1 ml of culture medium containing 1.5 × 10 ⁵ pigment cells, and 3.8 ml of Eagle's minimal nutrient medium containing 10% fetal bovine serum. The cells were cultured in a carbon dioxide incubator at 37°C for 6 days in air containing 5% carbon dioxide. In addition, as a control, pure water was added and cultured instead of the sample solution. The culture medium was removed from the pigmented cells that had been cultured for 6 days, and the cells were washed with Dulbets' choline buffer, followed by the addition of Dulbets' choline buffer containing 0.025% trypsin to detach the cells. Next, 4 ml of culture solution was added to the detached pigment cells to suspend them, and the number of cells was measured, followed by centrifugation at 1000 rpm for 10 minutes, and the degree of whitening of the pigment cells obtained was visually compared. -1 Test results The results are shown in Table 2-1, Table 2-2 and Table 2-3.

【table】

[Table] *: High degree of whitening, +: Slightly whitening, -: No whitening From the above results, the glucosamine derivative of the present invention has a stronger whitening effect on pigment cells than glucosamine hydrochloride, and it also shows that the glucosamine derivative of the present invention has a stronger whitening effect on pigment cells than glucosamine hydrochloride. kojic acid,
It was found to have a more whitening effect than ascorbic acid. Furthermore, whitening was observed with almost no cytotoxicity compared to hydroquinone. Note that N-merisinoyl-glucosamine, which has an acyl group with 30 carbon atoms, has a whitening effect comparable to that of glucosamine hydrochloride;
It was less effective than any of the following glucosamine derivatives having an acyl group. In particular, glucosamine derivatives having an acyl group having 1 to 8 carbon atoms showed a stronger whitening effect. Test Example 2 Regarding the whitened cells in Test Example 1, Test Example 1
The cells were cultured again without adding the test solution according to the test method described above, and the degree of whitening of the obtained cells was visually compared. -2 Test results Table 3 shows the results.

[Table] *: High degree of whitening, +: Slight whitening, -: No whitening From the above results, the glucosamine derivative of the present invention significantly suppresses melanin production in pigment cells;
It was found that the effect was reversible and did not adversely affect cell growth. In contrast, with conventionally known hydroquinone, pigment cells remained white even in re-cultivation without the addition of a test solution, and cell growth was also extremely poor. Test Example 3 Two or more test substances of Test Example 1 were mixed and cultured according to the test method of Test Example 1, and the degree of whitening of the obtained cells was visually compared. -3 Test results Table 4 shows the results.

【table】

[Table] *: Large degree of whitening, +: Slightly whitening, -: No whitening From the above results, the glucosamine derivative of the present invention has no effect on other reducing skin conditions even when one or more types are used. It was found that even when an anti-blackening substance was used together, the whitening effect was hardly affected. Test example 4 15 men and 15 women between the ages of 21 and 61, total 30
A closed patch test was performed on the flexor side of the upper arm of each subject. A 1% solution of the test substance of Test Example 1 was used as a sample. Judgment criteria -: No reaction at all, ±: Slight erythema,
+: Obvious erythema, ++: Erythema and swelling, papule-4 Test results The results are shown in Table 5-1 and Table 5-2.

【table】

【table】

〔Example〕

Next, examples of the present invention will be shown. The blending ratio is in parts by weight. Example 1 Skin lotion Polyoxyethylene (20) Monooleate 1.0 Ethanol 3.0 Polyethylene glycol 600 5.0 Citric acid 0.03 Sodium citrate 0.2 N-acetyl-1,3,4,6-tetra-O-
Propionylglucosamine 0.1 Methylparaben 0.1 Fragrance Appropriate amount Water Residual Example 2 Skin pack Polyvinyl alcohol 2 Ethanol 20 N-Butyryl-1,3,4,6-tetra-O-
Butyrylglycosamine 1 N-octanoyl-glucosamine 1 Glycerin 5 Fragrance Appropriate amount Water Remaining Example 3 Topical cream Beeswax 4.0 Stearic acid 5.0 Setanol 5.0 Lanolin 3.0 Pristane 3.0 Polyoxyethylene Sunaate 3.5 Glycerin monostearate 1.5 N-Octyl-1, 3,4,6-tetra-O-
Nactylglucosamine 5.0 Propylene glycol 10.0 Fragrance. Preservative Appropriate amount Water Residual Using the skin lightening cosmetic of the present invention and substances that prevent skin darkening such as ascorbic acid, kojic acid, and cinnamaldehyde, it is possible to prevent dark skin and spots on the upper arms of healthy men. , a use test was conducted to prevent freckles, and it was demonstrated that the fairing cosmetics of the present invention were extremely effective here as well. [Effects of the Invention] As detailed above, the present invention relates to a skin-lightening cosmetic that effectively contains a glucosamine derivative as an ingredient that prevents skin darkening. Compared to skin lightening cosmetics that contain substances that prevent skin darkening such as hydrogen, glutathione, colloidal sulfur, kojic acid, and cinnamaldehyde, this product is far more effective at preventing skin darkening caused by ultraviolet rays from sunlight. I can,
It has excellent effects such as preventing dark skin, age spots, and freckles, and beautifying the skin. It also has almost no cytotoxicity like hydroquinone, so it can be used safely without the risk of causing adverse effects such as vitiligo. It is.

Claims (1)

[Scope _of Claims] _{1 Formula [} Chemical _formula ]
A fair-skinned cosmetic containing one or more of the glycosamine derivatives represented by the following acyl groups as an active ingredient. 2 The amount of glucosamine derivatives contained in fair skin cosmetics
The fair-skinned cosmetic according to claim 1, which contains 0.001 to 10% by weight.