JPS61137817A - Remedy for hyperpigmentation disease - Google Patents

Abstract

PURPOSE:A mild remedy for hyperpigmentation disease, acting selectively on melanine-forming cell, showing improved decoloring effects, comprising cysteinylphenol, cysteiaminylphenol, or its derivative as an active ingredient. CONSTITUTION:A remedy containing cysteinylphenol or cysteiaminylphenol shown by the formula (R is cysteinyl or cysteiaminyl) or its derivative as an active ingredient. To be concrete, 4-S-cysteinylphenol, 2-s-cysteinylphenol may be cited as the derivative. The compound shown by the formula is milder than hydroquinone, acts selectively one a melanine-forming cell, and shows improved decoloring effects. The compound shown by the formula is usable in the form or cream, lotion, ointment, etc., by a conventional procedure. It is also effective against hyperpigmentation diseases such as chloasma facial, melasma. Addition's disease, etc.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to a therapeutic agent for pigment enhancement diseases.

[Conventional technology]

Pigment-enhancing diseases such as ovarian spots, Ajiran's disease, melasma, senile pigmentation, post-inflammatory hyperpigmentation, birthmarks, facial melanosis, and brown spots are caused by melanocytes, which are anti-Japanese melanocytes. Occurs based on abnormal performance. It is extremely difficult to treat these diseases, whether congenital or acquired. Currently known C
Drugs included include hydroquinone and its derivatives.

(Problems to be Solved by the Invention) However, although these drugs have excellent depigmentation effects, they are irritating to the skin, and in some cases, skin depigmentation may become permanent and when treated on the face, etc. ,
There is a drawback that the bleached area and the non-bleached area cause a mottled state.

The purpose of the present invention is to solve these problems and provide a therapeutic agent for pigment-enhancing diseases that is gentler, acts more selectively on melanocytes, and exhibits excellent depigmentation effects.

(Means for Solving the Problems) The above objects are achieved by the following present invention. That is, the present invention is a pigment-enhancing disease therapeutic agent containing cystinylphenol, cystyaminylphenol, or a derivative thereof as an active ingredient.

Cysteinyl phenol (cysteinyl phenol) of the present invention
lphenol), cystiaminylphenol.

Cysteaminylphenol is a compound represented by the following structural formula (R represents cystineal or cystyaminyl), specifically, 4-8-cystainylphenol, 2-
Examples thereof include 3-cystinylphenol, 4-8-cystyaminylphenol, and 2-8-cystyaminylphenol. These compounds are described, for example, in J.

Med, Chet24:673-677, 1
It can be synthesized by the method described in 981.

In addition, although the derivative is not particularly limited, derivatives to which q-cyclodextrin, β-cyclodextrin, etc. are bonded are preferred derivatives because they can make the above water-insoluble compounds water-soluble and can be applied to various preparations. be.

As derivatives, alkyl esters such as methyl esters of compounds having the above structural formula, 4-8-cystinylhydroquinone, 2-8-cystinylhydroquinone, etc. can also be used.

The pigment-enhancing disease therapeutic agent of the present invention can be formulated by conventional methods using these compounds together with excipients, diluents, and adjuvants as necessary, and can be formulated into creams, lotions, emulsions, powders, ointments, It can be used in the form of a gel or the like.

The content of the compound in each formulation is usually 1-10% per formulation.
It is used in the range of 0.5 to 30 IItg per day.

The therapeutic effects and toxicity of the present invention will be specifically illustrated below with reference to Examples.

Example 1 (Effect on black guinea pig skin melanocytes) 4-8-
Cystinylphenol and 4-8-cystyaminylphenol are each added to the water-absorbing ointment base (Japanese Pharmacopoeia).
(5% Wt/Wt) on black guinea pig skin.
200 Rg of the above blowing was applied once a day for 3M. The existing drug hydroquinone was used as a control. 4-
8-cystinylphenol and 4-8-cystyaminylphenol showed a depigmenting effect almost equivalent to that of hydroquinone, and the skin irritation effect was much less than that of hydroquinone.

Furthermore, it was confirmed using an optical microscope that the drug of the present invention selectively acts on skin melanocytes, and it was also confirmed that the melanin content in the skin was significantly reduced.

Example 2 (Effect on Riehl's melasma) 4-8-cystiaminylphenol was used in Example 1 on a 42-year-old female patient with Riehl's melasma who had dark brown pigmentation on the entire face. 5% (wt/
Wi) and applied to the face once a day.

The conventionally used hydroquinone application site and untreated site were selected as controls.

Two weeks after application, a remarkable skin bleaching effect began to be observed in the area where 4-3-cystiaminylphenol was applied. Its bleaching effect was significantly better than hydroquinone. After 4 weeks, there was a significant improvement, so I omitted some parts and applied 4 to the entire face.
-8-Cystyaminylphenol was started to be applied.

It was applied externally to the skin once a day for more than two months, but no local irritation was observed.

Furthermore, there were no effects such as lowering blood pressure, the general condition was good, and no side effects were observed.

Example 3 (Effect on melasma) The ointment base used in Example 1 was applied to the pigmented spot on the right side of a 60-year-old female melasma patient who had brown spots with relatively clear borders on the left and right tilted parts and lower jaw. An ointment containing 5% (wt/wt) 4-S-cystiaminylphenol was applied to the left side.
Hydroquinone was applied. Approximately one month after application, a ttq color effect of brown spots appeared, and 4-8-cystiaminylphenol showed the same effect as hydroquinone.

Additionally, take 4-3-cystiaminylphenol once a day.
Approximately 2 months after the treatment, the previously well-defined pigmented spots gradually approached the same color as the surrounding normal skin, and the borders became blurred. No irritation or inflammatory reactions were observed at the application site. Furthermore, no side effects were observed systemically.

Example 4 (R test) Using six black mice in each group, 4-8-cystinylphenol was dissolved in saline and administered intraperitoneally to examine acute toxicity. All up to 9 (10
0%) survived, and at a dose of 600 IRg/Kg, 4 animals (6
6%) survived and administered m 800 IFF/K9
t'31:'-t (50%) survived.

Claims (1)

[Claims] (1) A pigment-enhancing disease therapeutic agent containing cystineal phenol, cysteaminel phenol, or a derivative thereof as an active ingredient.