JPH08165244A - Dermatosis therapeutic agent - Google Patents

Abstract

PURPOSE: To provide a therapeutic agent for dermatosis involving pruritus such as atopic dermatitis and xeroderma, formulated with a local anesthetic, percutaneous absorption promoter and mucopolysaccharide polysulfate. CONSTITUTION: This dermatosis therapeutic agent contains, as active ingredients, 0.1-5wt.% of a local anesthetic (e.g. lidocaine and its hydrochloride), 1-10wt.% of a percutaneous absorption promoter (e.g. menthol) and 0.01-0.5wt.% of a mucopolysaccharide polysulfate (MPS). This agent is further formulated, according as appropriate, with an anti-inflammatory agent, antihistaminic agent, humectant, etc., and can be manufactured into a preparation in the form of gel, cream, lotion, milky lotion, etc. For a gel, this agent is formulated, as the base ingredients, with 0.1-5wt.% of a carboxyvinyl polymer, 0.02-3wt.% of a pH adjustor, and 20-70wt.% of water. This agent is formulated with 0.5-60wt.% of an oil ingredient, 0.1-25wt.% of a surfactant, and 20-40wt.% of water for a cream, while 0.1-25wt.% of a surfactant and 40-96wt.% of water in the case of lotion. Besides, this agent may also be formulated with auxiliary ingredient(s) such as antiseptic and/or antioxidant.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a therapeutic agent for skin diseases accompanied by itching caused by skin diseases such as atopic dermatitis and xerosis.

[0002]

2. Description of the Related Art At present, there is no fundamental treatment method for the treatment of skin eczema associated with itching such as atopic dermatitis.
Topical steroids and antipruritic drugs are used as coping therapy. Further, even if it is not a fundamental treatment, an external preparation containing urea is widely used in the dermatological field as a therapeutic drug for atopic eczema.

[0003]

Since atopic dermatitis is a chronic eczema, it is necessary to continuously use the drug. However, excessive intake of steroids causes fat deposits on the face, resulting in a so-called full moon-like face,
Side effects such as hirsutism and skin tears occur. Therefore,
Continuous use of topical steroids is difficult. In addition, it is difficult to prevent itching due to skin eczema with an external preparation containing urea, and since it increases the water retention of the keratin, it is necessary to use a high concentration of urea, so pain, erythema, desquamation, hypersensitivity, etc. May cause side effects.

[0004]

In view of such circumstances, the present inventors have diligently studied a preparation which has few side effects even if it is continuously used, suppresses itch, and replenishes dry skin with an appropriate amount of water. As a result, they have found that a preparation containing a local anesthetic, an absorption enhancer and a polysulfate of mucopolysaccharide can improve the symptoms of atopic dermatitis, and completed the present invention.

That is, the present invention is a therapeutic agent for skin diseases, which comprises a local anesthetic, a percutaneous absorption enhancer and a polysulfate of mucopolysaccharide.

The local anesthetics used in the present invention include lidocaine, dibucaine, bupivacaine, prilocaine, mepivacaine and their hydrochlorides. More preferable local anesthetics are lidocaine and its hydrochloride, and its compounding amount is preferably 0.1 to 5% by weight. As a percutaneous absorption enhancer, menthol, oleic acid, octyldodecanol, octyldodecyl myristate, and propylene glycol have a remarkable effect of promoting absorption of a local anesthetic, and the compounding amount thereof is preferably 1 to 10% by weight.

The polysulfate of mucopolysaccharide (hereinafter abbreviated as MPS) used in the present invention is a heparinoid substance extracted from the organs of animals, and has antithrombin action, anticoagulant action and peripheral blood circulation promoting action. At the same time, it is also known that it has an excellent moisturizing action, and its content is preferably 0.01 to 0.5% by weight.

In addition to the above components, the therapeutic agent for skin diseases of the present invention may contain anti-inflammatory agents such as glycyrrhizin, dipotassium glycyrrhizinate and glycyrrhetinic acid, and antihistamines such as diphenhydramine and isothipendyl hydrochloride. Also, glycerin as a moisturizer,
Polyethylene glycol, 1,3-butylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, polypropylene glycol, polyglycerin, and sorbitol aqueous solution can be used, but glycerin and 1,3-butylene glycol are preferable from the viewpoint of skin irritation. Is. The amount of these moisturizers is 0.5 to 20% by weight, preferably 1 to 10% by weight.

The composition for treating skin diseases of the present invention can be used as various external preparations such as gels, creams, lotions and emulsions. The base component of the present invention will be described in more detail below.

In the case of a gel, the blending amount of carboxyvinyl polymer is 0.1 to 5% by weight, preferably 0.3, from the viewpoint of physical heat stability, transparency, consistency and feeling of use of the gel. -1.5 wt% is compounded. Examples of the pH adjusting agent include inorganic bases such as sodium hydroxide, potassium hydroxide and aqueous ammonia, and organic bases such as triethanolamine, diethanolamine, diisopropanolamine, triisopropanolamine and arginine, and organic bases are particularly preferable. . The pH adjusting agent is added in an amount of 0.02 to 3% by weight so that the pH of the preparation is 3 to 9, preferably 6 to 8. The amount of water to be added may be appropriately adjusted depending on the other base, but it is 20 to 70% by weight, preferably 35 to 55% by weight.

The oil component of the cream agent can be selected from a wide range of natural to synthetic ones. For example, white petrolatum, liquid paraffin, solid paraffin, ceresin, microcrystalline wax, cholesterol, squalane, olive oil, mink oil, jojoba oil, Hydrogenated castor oil,
Hydrogenated coconut oil, beeswax, stearic acid, palmitic acid,
Lauric acid, stearyl alcohol, cetyl alcohol, lauryl alcohol, oleyl alcohol, isopropyl myristate, glyceryl monostearate, propylene glycol monooleate, glyceryl monooleate, sorbitan monocaprate, glyceryl monostearate, distearate distearate Glycerin,
Decaglyceryl monolaurate, silicone oil and the like can be mentioned, and these can be used alone or as an arbitrary mixture. The amount of these oil components is 0.5-
The amount is 60% by weight, preferably 1 to 40% by weight.

Surfactants used in creams and lotions include polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyglycerin alkyl phenyl ether, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil and the like. Examples thereof include nonionic surfactants and surfactants derived from natural products such as casein, saponin, phospholipids and glycopeptides, and these can be used alone or as an arbitrary mixture. The content of these surfactants is 0.1 to 25% by weight. The amount of water to be added is not particularly limited, but in the case of a lotion, it is 4
0 to 96% by weight, and 20 to 40% by weight in the case of cream.

In addition to these base components, auxiliary components such as antiseptics and antioxidants can be appropriately added to the composition of the present invention. As a preservative, methylparaben,
Ethylparaben, propylparaben, butylparaben,
Examples include thymol, chlorcresol, orthophenylphenol, and isopropylmethylphenol.
Examples of antioxidants include dibutylhydroxytoluene, erythorbic acid, and tocopherol acetate.

[0014]

EFFECTS OF THE INVENTION A therapeutic agent for skin diseases containing a local anesthetic, a percutaneous absorption enhancer and MPS obtained by the present invention is an atopic skin disease that is a chronic refractory skin disease due to the suppression of itch and an excellent moisturizing effect. It is useful as a therapeutic agent for dermatitis and xerosis.

[0015]

EXAMPLES The present invention will be specifically described with reference to Examples and Test Examples.

Examples 1 to 11 and Comparative Example Each of the components shown in Table 1 was blended and prepared according to the manufacturing method of the Japanese Pharmacopoeia Lotion of the First and Second Amendments.

[0017]

[Table 1]

Example 12 The following components were each mixed and prepared according to the above-mentioned example. Lidocaine 3 (wt%) MPS 0.3 Diphenhydramine hydrochloride 1 Lecithin 2 Nikkor TS-10 1 Liquid paraffin 5 Glycerin 3 1,3-Butylene glycol 3 Octyldodecanol 3 Carboxyvinyl polymer 0.1 Purified water Total 100 g Preparation.

Example 13 The following components were each mixed and prepared according to the above-mentioned example. Lidocaine 1 (wt%) MPS 0.3 Diphenhydramine hydrochloride 2 Lecithin 1 Nikkor TS-10 1 Squalane 5 Oleic acid 3 1,3-butylene glycol 10 Carboxyvinyl polymer 0.1 Prepared to a total of 100 g of purified water.

Example 14 The following components were each mixed and prepared according to the above-mentioned example. Lidocaine 3 (wt%) MPS 0.3 Diphenhydramine hydrochloride 1 Dipotassium glycyrrhizinate 1 Menthol 0.5 Medium-chain fatty acid triglyceride 3.5 Glycerin 5 1,3-butylene glycol 5 Carboxyvinyl polymer 0.2 Stearic acid 0.5 Purified water Prepared to be 100g.

Test Example 1 With respect to the preparations of Examples 1 to 11 and Comparative Example, a skin permeation test of lidocaine was carried out using the skin of the abdomen of hairless rats. The excised skin is sandwiched between two-chamber diffusion cells, 20 μl of the preparation is applied to the open stratum corneum, and 3 ml of purified water is applied.
The amount of lidocaine was quantified by sampling over time from the receiving tank containing the. FIG. 1 shows the result of blending the absorption enhancer 1 component, and FIG. 2 shows the result of blending the absorption enhancer 2 component. Comparing the cumulative transmission amount after 7 hours with the comparative example,
In Examples 1 to 5 of FIG. 1, the accelerating effect was 2.8 to 4.5 times, and in FIG. 2, Example 11 was 6.6 times, which was the most excellent accelerating effect.

Test Example 2 The preparations of Examples 6 and 11 and Comparative Example were subjected to a local anesthetic efficacy test in humans. 10 preparations on flexion side of forearm
It was applied in an amount of μl / 8 cm ² and the sensation of pain when the skin was stimulated was evaluated. Pain is evaluated by push-pull gauge (AIKO
The conical tip of H CPU GAUGE 14978) was pressed against the skin with a force of 5 g, and the pain sensation at that time was scored.
The measurement was performed every 30 minutes up to 4 hours from before and immediately after the application of the preparation. As for the sensation of pain, strong pain was 1 point, weak pain was 0.5 point, and no pain was 0 point, which was measured 10 times at one place and totaled. As shown in FIG. 3, the results show that the local anesthetic effect correlates with the results of the skin permeation test of Test Example 1, and particularly Example 11 showed an excellent local anesthetic effect.

[Brief description of drawings]

FIG. 1 shows the results of measuring the skin permeation of lidocaine using the abdominal excised skin of hairless rats for the formulations of Examples 1 to 5 and Comparative Example.

FIG. 2 shows the results of measuring the skin permeation of lidocaine using the skin of the abdomen of hairless rats for the preparations of Examples 6 to 11 and Comparative Example.

FIG. 3 shows the results of measuring the local anesthetic efficacy in humans for the formulations of Examples 6 and 11 and Comparative Example.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Fumio Urushizaki 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd.

Claims (2)

[Claims] 1. A therapeutic agent for skin diseases, which comprises a local anesthetic and a polysulfate of mucopolysaccharide. 2. A skin disease according to claim 1, wherein one or more of menthol, oleic acid, octyldodecanol, octyldodecyl myristate, and propylene glycol are added as a percutaneous absorption enhancer of a local anesthetic. Therapeutic agent.