JPS6330406A - Agent for external use - Google Patents

Abstract

PURPOSE:To obtain an external agent having excellent melanin-suppressing effect (skin-beautifying effect) and high safety, by compounding castanospermine as an active compound. CONSTITUTION:The objective external agent having remarkable skin-beautifying effect and high safety can be produced by adding preferably >=0.01wt%, especially 1-20wt% castanospermine of formula as an active component to various external agents such as ointment, gel, pack, cream, foundation, sebaceous gland activation cosmetic, etc. The melanin-suppressing and skin-beautifying effects of the above active component are absolutely different from those of conventional skin-beautifying agent and are supposed to be based on the conversion of the sugar chain of tyrosinase to suppress the development of tyrosinase activity. The above external agent may be compounded with other drug-active components such as anti-inflammatory analgesic agent, etc., in addition to the above active component. Especially, the effect can be promoted by the addition of a substance capable of improving the increasing tendency of melanin in epidermis by delaying the keratinization of cuticle.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an external preparation, and more particularly to an external preparation having a whitening effect.

[Conventional technology and its problems]

Pigmentation such as age spots, freckles, melasma, and sunburn tends to occur and increase with age, and becomes more difficult to disappear, and has become one of the skin concerns of middle-aged and elderly people.

The onset mechanism of these hyperpigmentation disorders has not yet been clearly demonstrated, and ultraviolet rays, melanocyte-stimulating hormone (MS)
This is thought to be due to the advanced melanin synthesis function of melanocytes due to the effects of H). In addition, the tendency of delayed keratinization of epidermal keratinocytes (keratinocytes) due to aging delays the excretion rate of melanin to the outside of the epidermis, which, combined with the enhancement of melanin synthesis ability, increases the melanin concentration within the epidermis. In other words, it is thought that symptoms of clinically enhanced pigmentation occur. In addition, these pigmented areas are localized and have a clear difference from the surrounding normal skin color, suggesting localized melanin synthesis in epidermal melanocytes or modulation of the mechanism that controls melanin synthesis in melanocytes. Although this is thought to be the result of this, there are many unknown factors.

There is a high demand for drugs that restore these acquired pigmentation areas to normal skin color, and many drugs have been developed and commercialized so far. Hydrogen peroxide, zinc peroxide, sodium peroxide, etc. were used, but these are extremely unstable and are said to have a bleaching effect.
In addition, almost no effect of reducing pigmentation was observed in practical use.

In recent years, cosmetics using vitamin C (L-ascorbic acid), which has excellent reducing ability, have also been used.
This also has problems with stability, and at present, it is hardly effective when used externally.

On the other hand, in treatment, no-hydroquinone and various catechols are used as drugs to treat age spots and whiten dark skin, but these also have safety problems such as irritation and allergies. It is not actually used because it can cause vitiligo.

Other melanin-suppressing and whitening agents have been reported or patent applications have been filed, but at present there are very few substances that have a substantial melanin-suppressing effect (whitening effect).
There has been a desire to develop a topical preparation that has excellent whitening effects and is highly safe.

[Means for solving problems]

Under such circumstances, the present inventors conducted intensive research to solve the above problems, and as a result, discovered that castanospermine has an excellent melanin suppressing effect, and completed the present invention. Therefore, the present invention provides a topical preparation containing castanospermine. Castanospermine, which is the active ingredient of the topical preparation of the present invention, has the structure of the following formula (1). It is a compound that is known to have the effect of inhibiting the processing process in glycoprotein bulk chain synthesis (A
Chieves of Biochemistry a
ndB10phy81e8 # vol -221*
A2 lPage 593-597 + Castanospermine is blended into various external preparations and exhibits an excellent melanin-suppressing effect. Therefore, castanospermine is blended into various external preparations and used in ointments, glues, etc. It can be made into various forms for each cosmetic such as a stimulant 1 or a cream, a foundation, a sebaceous gland activating cosmetic, and the like.

As for ointments, those based on oily bases, or those based on oil/water or water/oil type emulsion bases give particularly good results.

Here, the oil base is not particularly limited, and includes vegetable oil, animal oil,
Synthetic oils, fatty acids, natural or synthetic glycerides can be used.

The amount of castanospermine to be incorporated into the external preparation is not particularly limited, but is generally preferably 0.01 weight or more (hereinafter referred to simply as excellent) or more, with a weight of 0.01 to 20.

The external preparation of the present invention may contain other medicinal ingredients in addition to the above-mentioned active ingredients. For example, anti-inflammatory analgesics, side wound healing agents, moisturizers, anti-pruritic agents, which are expected to have a synergistic effect with the present invention,
Examples include bactericidal disinfectants, astringents, emollients, horsone agents, etc., and the effects are particularly enhanced by the combination of substances that improve the tendency for melanin to increase in the epidermis due to delayed epidermal keratinization.

[Action and effect of the invention]

The melanin-suppressing and whitening effects of castanospermine in the present invention are completely different from those of conventional whitening agents, and are thought to be based on changing the sugar chain of tyrosinase and suppressing the expression of tyrosinase activity. This whitening effect is remarkable and it is highly safe.

〔Example〕

Next, an example will be given and explained.

Example 1 Melanin production suppression test
10%, Fe2 (sential medium)
calf serum) +
Add 2 mM glutamate, 100 units/- of penicillin and 100 μt/- of streptomycin,
The cells were cultured at 37°C under the conditions of 5% CO2/95% air.

Castanospermine was added to B-16 mouse melanoma cells (5 Cultured.

After culturing, remove the medium, wash with phosphate buffer, and use rubber? Cells were collected using a squirrel, centrifuged at 800 r, p, m for 5 minutes, and the precipitate (cells) was collected and washed again with phosphate buffer. For quantification of melanin, 1M HzSOa was added to the precipitate, 20 μl of 3% KMn 04 was added several times with shaking, and then 100 μJ of 10% NaxSO3 was added. PCTA (Py) produced from melanin in this way
rrole-2e 3 * 5- tricarbox
ylic acid) was extracted twice with 6-diethyl ether and quantified by liquid chromatography.

Table 1 shows the results.

Table 1 Example 2 The following external preparations were prepared. When these external preparations were used twice a day for 3 months, pigmentation caused by melanin production in the epidermis, such as melasma and diffuse pigmentation, was improved in all cases. Spermine 5.0 Glycerin
4.0 yen? Lioxyethylene hydrogenated Hifushi oil 1.5s Ethanol 1
0.0 yen Sodium pyrrolidone cargonate 2
．． 0% fragrance
0.216 Purified water balance 10
0.01! (Shin) Oil Essence Castanospermine 5.0% Mink Oil
55.0% wheat germ oil
40. Ochi 100.0% (ll+) 0/W Cream Castanospermine 5.0% Stearic Acid 2. O% cetanol
4.0% Vaseline
5.0% squalane 8.0%
Hardened oil 4.0 Glycerin monostearate 2.4% Butyl no 9 Lapen 0. lS methyl no Q
Lapen G, 1 cup glycerin
3.0s Zode■ Birenda Recall
3.0s Potassium hydroxide 0.2
%Fragrance 0.2% Purified water Balance 100.0s Ov) Ointment Castanospermine 5.0% White petrolatum 95.0% 100.0% or more

Claims (1)

[Claims] 1. General formula ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ An external preparation containing castanospermine represented by