JPH0482834A - Remedy for dyspigmentation - Google Patents

Abstract

PURPOSE:To obtain the subject effective remedy for intractable dyspigmentation such as endogenous liver spots, senile mole or pigmented mole after inflammation free from side effects by using a galactosamine and/or a mannosamine as the active components. CONSTITUTION:Galactosamine or its salt and/or mannosamine or its salt is blended as an active component, e.g. in case of percutaneous administration, in an amount of 0.01-20 wt.%, preferably 0.1-10wt.% on their total amount base to obtain the objective remedy for dyspigmentation applied to a diseased part mainly by percutaneous administration and capable of remarkably effective remedy of dyspigmentation, e.g. senile mole the remedy of which was said to be difficult until now and in which a change for the worse is said to cause serious symptoms such as canceration, sunrays-causing mole due to exposure to excessive sunrays, pigmented mole after inflammation and endogenous liver spots not caused from an external stimulation such as sunburn without a side effect.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a therapeutic agent for hyperpigmentation, and more specifically, it relates to senile lentigines, solar lentigines, and solar lentigines, which have traditionally been difficult to treat. The present invention relates to a drug that effectively treats pigmentation diseases such as post-inflammatory pigment spots and intrinsic melasma that are not caused by external stimuli such as sunburn, without side effects.

[Conventional technology and its problems]

Continuous oral administration of vitamin C is used to treat pigmentation disorders such as intrinsic melasma, senile lentigines, solar lentigines, and post-inflammatory pigment spots, but the degree of pigmentation In advanced cases, continuous oral administration of vitamin C often does not improve the condition.

Furthermore, hyperpigmentation is caused by an abnormal increase in the amount of melanocytes within the epidermis, and this is caused by an increase in the number of melanocytes and their enhanced function. As a method to suppress the excessive production of melanin and prevent the effects of ultraviolet rays that enhance melanocyte function, substances that scatter light such as powders such as talc, zinc white, and titanium oxide, or ultraviolet absorbers such as para-aminobenzoic acid are used. A method using ointments, etc. containing

It is also known to use external preparations containing substances that inhibit melanin production in the epidermis, and depigmenting agents such as ascorbic acid and glutathione.

However, these topical preparations are mainly intended to prevent pigmentation that increases due to sunlight, and even if these topical preparations are used alone, no significant improvement can be expected as a treatment for pigmentation disorders. Can not.

The applicant has been conducting research in search of an effective drug for the treatment of hyperpigmentation, and has been researching drugs containing kojic acid as an active ingredient (
Japanese Patent Application No. 1-161155), combination of placenta extract and kojic acid or kojic acid derivative (Japanese Unexamined Patent Publication No. 63-8310), combination of zylodextrin and kojic acid (Japanese Unexamined Patent Publication No. 63-8311) ), combination of placenta extract and ergothioneine (JP-A-63-8335), combination of placenta extract and liver extract (JP-A-1-38774)
, a drug containing liver water extracts of mammals and birds as an active ingredient (Japanese Unexamined Patent Publication No. 63-8313) has been shown to be effective as a melanin production suppressing topical drug used in topical therapy for hyperpigmentation. Ta.

In the process of further testing these inventions and continuing research in search of a drug that is effective as a pigmentation treatment, the present inventor has previously discovered methods for suppressing melanin production, as seen in Japanese Patent Application Laid-Open No. 1-143814. Galactosamine or its salts and/or mannosamine or its salts, which were only known to be effective as agents, can be used to treat senile lentigines, solar lentigines, post-inflammatory pigment spots, and sunburn, which have completely different mechanisms of onset. The present invention has been completed based on the finding that hyperpigmentation diseases such as endogenous melasma, which are not caused by external stimuli such as acne, can be effectively treated without any side effects.

[A means of saving to solve problems]

That is, according to the present invention, a therapeutic agent for pigmentation disorder containing galactosamine or its salts and/or mannosamine or its salts as an active ingredient is provided.

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

Intrinsic melasma is not extrinsic melasma caused by normal sunburn, but is intrinsic melasma caused by hormonal abnormalities or taking various drugs for treating internal diseases, and is an intractable pigmentation disorder.

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 the active ingredients galactosamine, mannosamine, and their salts contained in this transdermal preparation is 0.
01 to 20% by weight, preferably 0.1 to 10% by weight, and even when each component is used in combination, the total amount may be within the above range.

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

The toxicity of galactosamine, mannosamine and their hydrochlorides, which are the active ingredients of the present invention, is extremely low, and the LD5
0 is an extremely safe drug, with doses of 2.030 mg/kg or more for mice and 2,210 mg/kg or more for rats when administered subcutaneously.

〔Example〕

Hereinafter, the present invention will be explained in detail with reference to Examples.

Example 1 Liquid agent D-Garak glycerin Sorbitol stearic acid ethanol Sodium bisulfite EDTA Ninatori Sodium glutamate purified water Mix and stir each ingredient, do.

Example 2 D-mannosamine Propylene glycol ascorbic acid purified water soy lecithin emulsion lotion (weight%> Tozamin 20 5.0 Lioxil 40 1.55 10.0 Ram 005 Ram 0.02 Rium 0.5 ~100 Dissolve these and make a liquid (weight%) 0.8 dl-α-tocopherol ethanol polyethylene glycol 400 purified water purified water EDTA disodium Sodium hydrogen tartrate Mix and stir each component of ASB and C, It is dissolved to make an emulsion lotion.

Example 3 Oil ointment D-Mannosamine hydrochloride polysorbate 20 Dextran ethanol White petrolatum Tallow cetanol 0.2 Dissolve these (wt%) ~100 20.0 di-α-tocopherol 0.1 Glycerin monostearate 50A are stirred and mixed. . B is heated, mixed and stirred, and when cooled, A is mixed to obtain an oil-based ointment.

Example 4 Water-soluble ointment (wt%) Carboxyvinyl polymer 1.0 Propylene glycol 100 Ethanol
8,0 diisopropanolamine 0
．． 15 Triacetin 30.0 Xanthan Gum 2.0 Purified Water
3.0 Sodium Bisulfite
0.03 purified water
~100D-galactosamine hydrochloride 1.5
8. Mix and dissolve to make a gel. Then, B, C and D are sequentially added to A to prepare a water-soluble ointment.

Example 5 Emulsion ointment (wt%) White petrolatum 25.0 Silicone oil
50 stearyl alcohol
22.0 Propylene glycol 120
Sucrose fatty acid ester 5,0 Polyoxy stearate 40 2.5d1-α-tocopherol 0.15D-mannosamine hydrochloride
5.0 Purified water ~1
00 Each component is mixed uniformly while heating and cooled to form an emulsion ointment.

Example 6 Cream (wt%) Δ Purified water ~100 1.3-Butylene glycol 3.0 Sorbitol
7.0dl-PCA sodium (50
% liquid) 3.0 carboxyvinyl polymer 00
5 Polysorbate 60 2.5 Monostearic acid glyceride 1.5 Secnor
3.0 Vaseline
5.0 Octyldodecyl myristate 5
．． 0 Octyldodecanol 6.0 Squalane 11.0 d1-α-tocopherol 0.15 Purified water
10, OD-mannosamine hydrochloride
2.0 Heat and dissolve A and B, add B to A, emulsify, and cool to make cream. Separately, C is dissolved and added to the cream.

Example 7 Aerosol (wt%) D-
Galactramine hydrochloride 2.0 cetanol
1,2 propylene glycol
4.0 stearic acid
80 Purified Water ~100 Freon 123/141b (57:43) 7.0
Each component is mixed and dissolved and placed in an aerosol container to form an aerosol.

Example 8 Poultice (wt%) Polyacrylic acid 30.0 Sorbicune monooleate 1.0 Purified water
~100 Sodium polyacrylate
7.0 Ammonium chloride 0.3 Concentrated glycerin 20.0 Titanium oxide
4. OD-Mannosamine
2. OD-galactosamine
3.0 AB is 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 Styrene-polyisobutylene-polystyrene rubber shown as plastic agent (wt%)
40.0 liquid paraffin
250 Ester Gum 150 Polybutene 15,0 Butyl Hydroquine Toluene 1. DD-mannosamine hydrochloride 5. OD-galactosamine hydrochloride
Heat and melt 50Δ, add B little by little and stir evenly. After gradually adding C to this, it is spread into a coating agent to form a plus coating agent.

Next, using the drug of the present invention, endogenous melasma, senile lentigo,
The results of a clinical trial regarding the therapeutic effects of post-inflammatory pigment spots are shown.

Clinical test (1) Test sample cream of Example 6 ■ (2) Target patients Patients visiting university hospital, 53 patients with intrinsic melasma, 18 senile lentigines
21 people had post-inflammatory pigment spots.

(3) Test method Twice a day (in the morning and before bedtime), apply the test sample 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 disappeared.

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

Chapter 1 Table The numbers in the table indicate the number of people.

In this study, the treatment period was as early as one month, and the effect was seen after four months at the latest.

〔Effect of the invention〕

According to the present invention, treatment of endogenous melasma, senile lentigines, solar lentigines, post-inflammatory pigment spots, etc., which have been considered difficult to treat and whose worsening is said to cause serious symptoms, can be treated. It is possible to provide a drug that cures hyperpigmentation very effectively and without side effects.

Claims (1)

[Claims] 1. A pigmentation treatment agent characterized by containing galactosamine or its salts and/or mannosamine or its salts as an active ingredient.