JPS638335A - External preparation suppressing melanin formation - Google Patents

Abstract

PURPOSE:An external preparation suppressing melanin formation useful against chromatodermatosis such as chloasma, etc., containing an extracted solution of placenta and ergothioneine as active ingredients. CONSTITUTION:An external preparation containing an extracted solution of placenta (e.g. extracted solution of human placenta) and ergothioneine as active ingredients. Continuous internal use of vitamin and use of ointment containing ultraviolet light absorber or external preparation containing decoloring agent as external therapy are known as a therapy against chromatodermatosis such as chloasma, etc., but no therapy has provides satisfactory effects. Ergothioneine and the extracted solution of placenta individually show inhibitory action on melanin formation, exhibit different action mechanisms and it is considered that improved melanin suppressing effects are obtained by the synergistic effects of both the substances. The amounts of the active ingredients to show sufficient effects are 0.01-5wt% based on the whole drug of ergothionine and 0.1-10wt% extracted solution of placenta.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a melanin production inhibiting topical drug used for topical treatment of pigmentation disorders such as melasma.

(Conventional technology) Continuous oral administration of vitamin C has been used as a treatment for pigmentation disorders such as melasma, but once the degree of pigmentation has reached a certain level, continuous oral administration of vitamin C is insufficient. In many cases, it does not improve.Additionally, as a topical therapy, hyperpigmentation is thought to be caused by an increase in the amount of melanocytes in the epidermal cells caused by the enhancement of melanocyte function, and as a way to suppress this excessive production of melanin, it is recommended to enhance melanocyte function. As a method of preventing the effects of ultraviolet rays, methods have been used to use substances that scatter light rays, such as powders such as talc, zinc white, and titanium oxide, or ointments containing ultraviolet absorbers, such as para-aminobenzoic acid.

It is also known to use an external preparation containing a depigmenting agent such as a substance that suppresses melanin production in the epidermis, hydroquinone, or a hydroquinone derivative.

Furthermore, a fair skin cosmetic containing ergothioneine is disclosed in Japanese Patent Publication No. 55-27883.

Furthermore, cosmetics containing placenta extracts have also been disclosed (Japanese Patent Publication No. 15399/1983).

[Problem that the invention seeks to solve]

In the prior art, light blocking agents used in external drugs for topical treatment of pigmentation disorders are used to prevent pigmentation from increasing due to sunlight;
It is used in conjunction with other therapies, and if used alone, it cannot be expected to be effective as a topical drug for pigmentation disorders.

External preparations of hydroquinone and hydroquinone derivatives (hydroquinone monobenzyl ether, etc.) used as depigmenting agents may cause patchy or reticular vitiligo as a side effect, and are not preferred as external treatments for pigmentation disorders and the like.

An object of the present invention is to provide an external drug that sufficiently suppresses melanin production for use in external treatment of pigmentation disorders and the like.

[Means for solving problems]

The present invention is a melanin production suppressing topical drug f that contains placenta extract and ergothioneine and has a remarkable effect on skin diseases such as hyperpigmentation.

Ergothioneine used in the present invention is a known compound having the following structural formula.

C0〇- This substance is known to be contained in the human body's blood and organs such as the liver. , D. H. Horner, Earl Levshec)] (D, 8. Melvi
le, W, H, Horner, R, Lubsch.
ez ; J, Biol, Chem.

206221P 1954), and its synthesis method has also been reported [Journal of Chemical Society 2215M 1951 (H, Heath, A. Roanson, C. Rimington)] (H, Heath,
A. Lawson.

C, Rimington; J, Chem, Soc, 2
215P, 1951).

In the present invention, both extracted and purified products and synthetic products from the above-mentioned organisms can be used.

The ratio of the above placenta extract and ergothioneine is 10 parts (by weight) of placenta extract to 5 to 5 parts ergothioneine.
0.01 (weight) is suitable.

The proportion of these active ingredients in topical drugs is approximately 0.1 to 10% (by weight) for placenta extract and 0.01 to 5% (by weight) for ergothioneine, which is sufficient to achieve its effect. be able to.

The external medicines of the present invention are mainly emulsions, lotions, soft pages, and the like. Each of these preparations contains the above-mentioned active ingredients as a base commonly used in each preparation.

It is formulated using auxiliary agents and other commonly used methods.

Next, a test example showing the inhibition of melanin production by the melanin production-inhibiting topical drug of the present invention will be given.

(1) Tyrosinase inhibition test (test method) In a test tube, add L-dopa solution (lomM) I m/Mafkulhein buffer (pH 6, !3) 0.9 m! Add sample 1d and incubate for 10 minutes in a thermostatic water bath at 37°C. Then add tyrosinase activity 1 (11.0OOG above li" of B16 mouse melanoma) 0.1-, stir well, and immediately check spectrophotometry. Set it on the meter, 47
Absorbance at 5 nm was measured over time.

The samples are placenta extract, 0.1% ergothioneine, placenta extract containing 0.1% ergothioneine, and water as a control. Note that the inhibition rate is the percentage of inhibition of dopachrome production after 8 minutes when the control is set as 100.

The above measurement results are shown in the attached drawings. As is clear from the figures, the combination of ergothioneine and placenta extract inhibits tyrosinase activity more effectively than either alone.

Although it is known that ergothioneine and placenta extract, which are the active ingredients of the present invention, have the effect of inhibiting melanin production even when used alone, the inventor's research has shown that ergothioneine and placenta extract have the effect of inhibiting melanin production. As a result of analyzing the mechanism of inhibition of melanin production, it was found that ergothioneine inhibits melanin production by chelating with copper ions and suppressing tyrosinase activity, which is involved in the initial stage of melanin production. It was demonstrated that the placental extract did not show copper ion chelation, and that the mechanism of melanin production suppression in the placental extract was different from that of ergothioneine. As a result, it is thought that the synergistic effect of ergothioneine and placenta extract is obtained due to their different melanin production inhibiting effects.

(2) Human skin FJ application test (test method) A snow cloth test of the ointment of the present invention was conducted on 60 patients with age spots and sunburn at three hospitals, A, B, and C.

The final judgment was made by visual observation 3 months after the start of application. Invalid: Whitening is not observed.

Slightly effective: Slight whitening is observed.

Effective: Those with obvious whitening.

Effective results: Complete recovery or something close to it.

It was judged as.

Based on the above results, a total of 60 patients at three hospitals, 4 with high fever,
The results were moderately effective in 11 patients, effective in 33 patients, and excellent in 12 patients. The total efficacy rate was 93.5 for 56 patients, ranging from moderately effective to excellent efficacy.
It was 33%.

〔Example〕

Next, examples of the present invention will be described.

Example 1 (Ointment) Polyethylene glycol monostearate (40E, o
,)2. OOg, self-emulsifying glyceryl monostearate 5.00 g, stearin MS-00g, behenyl alcohol 1. OOg, liquid paraffin 10.00 g
, 10.00 g of glyceryl trioctanoate, and 0.20 g of paraoquine benzoic acid methyl ester were dissolved by heating.

A heated solution of 5.00 g of 1.3-butylene gellicol and 51.8 g of purified water was added to this, emulsified, stirred, and cooled. 2. Ergothioneine was added to the emulsion thus obtained.
Add 0g of human placenta extract and 8.0g of human placenta extract, mix and stir, cool, and then fill in a container to obtain a product after testing.

Example 2 (Emulsion) Polyoquine ethylene sorbitan monostearate (20
E, O,) 1.00 g, polyoxyethylene sorbinotetraoleate (60E, O,) 0.50 g,
Lipophilic glyceryl monostearate 1. OOg, stearic acid 0.50g, behenyl alcohol 0.50g,
Avocado oil 4.0Og, glyceryl trioctanoate 4.
OOg, paraoxyammonium, fragrant methyl ester 0.20
Dissolve g by heating. In addition, 5.00 g of 1,3-butylene glycol, 0.14 g of xanthan gum, 1.0 g of ergothioneine, 5.0 g of placenta extract, and 77 g of purified water.
Add 16 g of the heated solution, stir to emulsify, and cool.

Add a small amount of fragrance to this liquid and stir to mix. After cooling the liquid obtained in this way, it is filled into a container and used as a product after inspection.

Example 3 (Lotion) Add 0.5 g of ergothioneine, 3.0 g of human placenta extract W, 0.10 g of tohaloxybenzoic acid methyl ester, 0.01 g of hyaluronic acid, a trace amount of fragrance, and purified water, and bring the total amount to 10 g.
0g, stir and mix, fill in a container, and use as a product after inspection.

The melanin production inhibiting topical drug of the present invention is used as appropriate depending on the symptoms, but it is generally effective by applying it to the affected area three times a day after washing the face.

〔Effect of the invention〕

By applying the topical drug of the present invention to the affected area, the synergistic action of ergothioneine and placenta extract can cause
It is extremely effective in the prevention and treatment of pigmentation disorders caused by melasma and the like.

[Brief explanation of drawings]

The figure shows the dopachrome production of the active ingredient of the invention.

Claims (1)

[Scope of Claims] 1. An external drug for suppressing melanin production, characterized by containing placenta extract and ergothioneine. 2. The melanin production inhibiting topical drug according to claim 1, wherein the placenta extract is a human placenta extract.