JPH0436217A - Therapeutic agent for pigmentation - Google Patents

Abstract

PURPOSE:To obtain a therapeutic agent containing allomatol which is a kojic acid derivative as an active ingredient and useful for endogenous chloasma, senile lentigo, solar lentigo and post-inflammatory pigmental spot which are regarded as intractables. CONSTITUTION:A drug, containing allomatol (a kojic acid derivative) expressed by the formula as an active ingredient and capable of effectively treating senile and solar lentigo, post-inflammatory pigmental spot, etc., endogenous chloasma, etc., occurring without originating from the irritation by the external world. The allomatol is obtained by converting hydroxymethyl group of the kojic acid into chloromethyl group, then converting the resultant group into methyl group by reductive reaction. Since the aforementioned drug can be applied to affected parts mainly by percutaneous administration, the drug is prepared in the form of ointments, solutions, lotions, creams, aerosols, cataplasmas, plasters, etc. The above-mentioned drug is safe and extremely effectively cures the pigmentation without any side effects.

Description

[Detailed Description of the Invention] [Industrial Application Field] Kitoda relates to a pigmentation treatment agent, and more specifically, it is used to treat senile lentigines, solar lentigines, and post-inflammatory lentigines, which have traditionally been considered intractable. The present invention relates to a drug that safely and effectively treats pigmentation diseases such as endogenous melasma that are not caused by external stimuli such as pigment spots and sunburn.

[Conventional technology]

Conventionally, skin liniments that thin out freckles that appear on the skin surface due to external stimuli such as sunburn have used bleaching substances such as hydroquinone, and melanin production inhibitors such as kojic acid. It is known to use

However, these melanin production inhibitors are aimed at suppressing the above-mentioned symptoms caused by external stimuli, and are used to treat senile lentigines, solar lentigines, post-inflammatory pigment spots, and other symptoms that are not caused by external stimuli. An effective therapeutic agent for endogenous melasma and the like is not yet known.

[Problem to be solved by the invention]

As mentioned above, Mokutoda effectively treats senile and solar lentigines, post-inflammatory pigment spots, and endogenous melasma that occur not due to external stimuli, which are considered incurable to date. The aim is to provide a drug that

[Means to solve the problem]

As a result of intensive research in order to solve the above problems, the present inventor has
Obtained knowledge that kojic acid is effective against the above symptoms,
A patent application was filed as Japanese Patent Application No. 1-161155. Thereafter, in the process of further testing the above invention, it was discovered that allomaltol, a derivative of kojic acid, was more effective than kojic acid for the above symptoms, and the present invention was completed.

That is, the present invention requires a therapeutic agent for endogenous melasma, senile lentigines, solar lentigines, and post-inflammatory pigment spots, which contains allomaltol as an active ingredient.

Senile lentigines associated with skin aging and solar lentigines that develop as a result of excessive exposure to sunlight, which are the diseases targeted by the drug of the present invention, develop symptoms as the number of melanocytes in the skin increases. It is a disease that can worsen and eventually turn into cancer. Post-inflammatory pigment spots are dark brown pigment spots that remain after the healing of some skin disease and are an intractable disease.

In addition, intrinsic melasma is not extrinsic melasma caused by normal sunburn, but is intrinsic melasma caused by hormonal abnormalities or the use of various drugs to treat internal diseases, and is also an intractable pigmentation disorder. .

Allomaltol of the present invention is a kojic acid derivative represented by the following formula, and is derived from kojic acid through a two-step reaction.

That is, the hydroxymethyl group of kojic acid is converted to a chloromethyl group, and then converted to a methyl group by a reduction reaction.
Get allomaltol.

This substance has a melanin production inhibiting effect and is used in skin-fairing cosmetics and the like.

Since the drug of the present invention is mainly applied to the affected area by transdermal administration, its formulation forms include ointments, solutions, lotions, creams, aerosols, poultices, plasters, and the like. The formulation is made into a transdermal drug using a conventional formulation method using auxiliaries, additives, spreaders, etc. that are commonly used in these formulations.

The content of allomaltol, which is an active ingredient contained in this transdermal preparation, is 0.1 to 20.0% (weight), particularly preferably 0.5 to 5% (weight).

When using this transdermal drug, usually twice a day (in the morning,
Apply an appropriate amount to the affected area (before going to bed).

Next, the results of clinical trials regarding the therapeutic effects of the present invention on endogenous melasma, senile lentigines, and post-inflammatory pigment spots will be shown.

Clinical test (1) Test sample Cream prepared in Example 6 (2) Target patients University hospital patients, 57 patients with intrinsic melasma, senile lentigines
17 people, post-inflammatory pigment M 20 people, total 94 people.

(3) Test method Twice a day (in the morning and before bedtime) Apply the test reagent to the left side of the affected area of the face.
．． A sufficient amount of 5 g was applied, and the right side was not applied and tested as a control.

(4) Judgment After application, the left side (treated side) and right side (non-treated side) were compared over time to visually judge the treatment status.

The criteria for evaluation were as follows.

Significant results: Most of the pigment spots have faded.

Effective: Something judged to be quite effective.

Slightly effective: Pigmentation has slightly faded.

(5) Results The results were as shown in Table 1 (7) below.

Table 1 Numbers in the table indicate the number of people. In this study, the treatment period was as early as 1 month, and the effect was seen after 4 months at the latest.

〔Example〕

Example 1 Liquid (wt%) Allomaltol 2,0 Glycerin
5.0 Sol High Tor

4.0 Stearic acid polyquine 40
1.55 ethanol 1
0.0 Sodium bisulfite 0.05
Rum: 0.02 Lium: 0.5 to 100 These are dissolved, and the liquid agent and EDTA, nina triglutamate, and purified water are mixed and stirred.

Example 2 Emulsion Lotion Aromaltol Propylene Glycol Ascorbic Acid Purified Water Soybean Lecithin dl-α-Tocopherol Ethanol Polyethylene Glycol 400 Purified Water Purified Water Disodium EDTA (wt%) 2.5 1.0 - 100 (wt%) 0 .8 0.1 5.0 6.0 20.0 (wt%) 1.0 0.02 Potassium hydrogen tartrate 0.2A, B,
The components of C are mixed and stirred to dissolve them to obtain an emulsion lotion.

Example 3 Oily ointment A (wt%) Aromaltol 30 Polysorbate 20
5.0 dextran
0.07 ethanol
5. OB (weight%)
White Vaseline ~100 Beef Tallow
20.0 cetanol
2.0dl-α-tocopherol
0.1 Glyceryl monostearate 5
．． Stir and mix the OA. B is heated, mixed and stirred, and when cooled, A is mixed to obtain an oil-based ointment.

Example 4 Water-soluble ointment A (wt%) Carboxyvinyl polymer 10 Propylene glycol 10.0 Ethanol
80 diisopropanolamine
015B (wt%) triacetin 300 xanthan gum 2. OC (wt%) Purified water 3.0 Sodium bisulfite 0.03D
(wt%) purified water
10.0 Allomaltol
1. Mix and dissolve the ingredients to make a gel. Then B
1C and D are sequentially added to A to form a water-soluble ointment.

Example 5 Emulsion ointment (wt%) White petrolatum 25.0 Silicone oil
5.0 stearyl alcohol
22.0 Propylene glycol
12.0 Yose sugar fatty acid ester 5.0
Polyoquine stearate 40 dl-α-tocopherol Aromaltol M water Each component is mixed uniformly while heating to form an emulsion ointment.

Example 6 Ream Purified Water 1.3-Butylene Glycol Sorbitol dl-PCA Sodium (50% Liquid) Carboquin Vinyl Polymer Polysorbate 60 Monostearic Acid Glyceride Cetanol Petrolatum Myristate Octyl Dodecyl Octyl Dodecanol 2.5 0.15 ~ 100 Cooling (wt%) ~100 3.0 (wt%) 1.5 5.0 5.0 6.0 Squalane 11,0d1-α
- Tocopherol 0.15C (wt%) Purified water 10.0 Aromaltol 2.0 ASB was dissolved by heating,
Add B to A, emulsify, and cool to form a cream. Separately, C is dissolved and added to the cream.

Example 7 Aerosol (wt%) Aromaltol 2.0 Cetanol
1.2 Propylene glycol
4.0 stearic acid
8.0 Purified water ~100
Freon 123/141b (57:43)
7. Mix and dissolve the 6 components and place in an aerosol container to make an aerosol.

Example 8 Poultice (wt%) Polyacrylic acid 30.0 Sorbitan monooleate 1.0 Purified water
~100 Sodium polyacrylate
7.0 Aluminum chloride 0.3
Concentrated glycerin 20.0 Titanium oxide 4.070 Maltol
5. OA and B are dissolved by heating, B is added to 8, stirred uniformly, and cooled. After cooling, it is applied to a liniment to make a poultice.

Example 9 Plastering agent (wt%) polystyrene-polyisoprene-polystyrene rubber
40.0 liquid paraffin
25. O ester gum 15.
0 Polybutene 15.0 Butylated hydroxytoluene 1.0 Allomaltol
4. Heat and melt OA, add B little by little and stir evenly. After gradually adding C to this,
Spread into a coating agent to make a plaster.

〔Effect of the invention〕

According to Koto, it is difficult to treat conventionally, and worsening of this disease can lead to pigmentation disorders such as intrinsic melasma, senile lentigo, solar lentigo, and post-inflammatory pigment spots, which cause serious symptoms. , a drug that is safe, has no side effects, and is extremely effective in healing is provided.

April 25, 1991

Claims (1)

[Claims] 1. A therapeutic agent for endogenous melasma, senile lentigines, solar lentigines, and post-inflammatory pigment spots containing allomaltol as an active ingredient.