JPH09157161A - Treating agent for skin disease - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a treating agent for skin diseases which contains a combination of bufexamac with crotamiton to newly develop analgesic action in addition to the increased anti-inflammatory action and is effective as a treating agent for skin diseases such as atopic dermatitis. SOLUTION: This treating agent comprises (A) bufexamac and (B) crotamiton. In an preferred embodiment, this treating agent contains 2.5-5wt.% of the composition A based on the whole preparation, the component B 2-5 times the weight of the component A, in an amount of 5-50wt.% in the whole preparation, in addition, (C) 0.1-2wt.% of an antihistamine such as diphenhydramine and (D) 0.1-2wt.% of a local anesthetic such as dibucaine hydrochloride. The dose of the objective treating agent is 10-50mg of the component A and 20-150mg of the component B every application.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic agent for skin diseases, and more specifically to a therapeutic agent for skin diseases which enhances the anti-inflammatory action of bufexamac and imparts an excellent antipruritic effect.

[0002]

2. Description of the Related Art With the westernization of eating habits, changes in living environment, increased stress, etc.,
An increasing number of people have various skin diseases, especially atopic dermatitis due to atopic diathesis. These skin diseases are generally treated with steroidal and / or non-steroidal external preparations.

However, the external preparations of steroid type have strong side effects, and if they are used continuously, they may adversely affect the skin condition. In addition, non-steroidal external preparations have weak side effects but low efficacy and are only used as an adjunct to steroidal external preparations.

[0004] The present invention has been made in view of the above circumstances,
It is an object of the present invention to provide a therapeutic agent for skin diseases that is highly effective against various skin diseases and has few side effects.

[0005]

Means for Solving the Problems and Modes for Carrying Out the Invention In view of the above-mentioned drawbacks of the prior art, the present inventors have eagerly aimed to improve the skin symptoms of patients with skin diseases and obtain a therapeutic agent for skin diseases with few side effects. As a result of repeated studies, the combined use of crotamiton with bufexamac, a nonsteroidal anti-inflammatory drug, improves the skin absorbability of bufexamac and enhances the anti-inflammatory effect of bufexamac. , Symptoms such as erythema, swelling, papules, erosion, crust and scale due to skin diseases are improved, and pruriticity peculiar to skin diseases is synergistically improved by the antipruritic effect of crotamiton, and it is unique to steroid external preparations. It was found that a therapeutic agent for skin diseases free of side effects such as local redness, burning sensation and tightness can be obtained, and the present invention has been completed.

The present invention will be described in more detail below. The therapeutic agent for skin diseases of the present invention is a combination of bufexamac and crotamiton.

The blending amount of bufexamac in the present invention is 2.0 to 10% by weight, preferably 2.
5 to 5% by weight. If it is less than 2.0% by weight, the effect is not exhibited, and if it is more than 10% by weight, it is meaningless in terms of effectiveness and may not be preferable in the production process of the product. In addition, the amount of crotamiton compounded is 2 times or more by weight of bufexamac, preferably 2 times or more and less than 5 times by weight, 2 to 30% by weight of the formulation in the formulation
Preferably it is 5 to 20% by weight. If the content of crotamiton is less than twice the weight of bufexamac, not only the transdermal absorption promoting action of crotamiton is not exhibited but also the antipruritic action is not exhibited, so that the effect may be reduced.
On the other hand, if it is blended in an amount of 5 times the weight or more, problems may occur in the stability of the preparation.

The agent for treating skin diseases of the present invention contains various active ingredients such as antihistamines, local anesthetics, fungicides and vitamins in addition to bufexamac and crotamiton in order to enhance the effectiveness against various skin diseases. it can.
As antihistamines that can be blended, 0.1 to 2% by weight of diphenhydramine hydrochloride, chlorpheniramine maleate, isothipendyl hydrochloride, diphenhydramine base, chlorpheniramine base and the like can be blended. As the local anesthetic, 0.1-2% by weight of dibucaine hydrochloride, isothipendyl hydrochloride, lidocaine hydrochloride, thecaine, dibucaine, lidocaine, ethyl paraaminobenzoate, etc. can be blended. As the bactericide, 0.05 to 1% by weight of benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, biozole, phenol or the like can be added.
As the vitamin preparation, tocopherol, tocopherol acetate, tocopherol nicotinate, nicotinic acid amide, pyridoxine hydrochloride, retinol, retinol palmitate, etc. can be added in an amount of 0.05 to 3% by weight. In addition, 0.1 to 5% by weight of menthol and / or camphor and the like can be added as a cooling agent to the therapeutic agent for skin diseases of the present invention.

The dosage form of the therapeutic agent for skin diseases of the present invention is arbitrary, and any dosage form such as solution type, emulsion type, cream type, ointment type and gel type may be used. Ingredients such as known excipients to be given can be blended.

The therapeutic agent for skin diseases containing bufexamac and crotamiton of the present invention, when applied to diseased skin, crotamiton promotes percutaneous absorption of bufexamac so that bufexamac has anti-inflammatory properties. As the effect is enhanced, the antipruritic effect of crotamiton,
Although it is possible to obtain a therapeutic agent for skin diseases, which has a strong effect of reducing symptoms such as erythema, papules, swelling, erosion, crust, scales and pruritus, which are peculiar to skin diseases, and which does not cause side effects like external steroidal agents. In this case, the therapeutic agent for skin diseases of the present invention is applied to the affected area about 1 to 3 times a day, and
Bufexamac is 10 to 50 times
mg and crotamiton can be 20 to 150 mg.

[0011]

EXAMPLES The present invention will be described below in detail with reference to examples and comparative examples, but the present invention is not limited to the following examples.

[Examples 1 and 2, Comparative Examples 1 and 2] With respect to the formulations shown in Table 1, the oil phase part of A heated to 70 ° C. was added to the water phase part of B similarly heated to 70 ° C. to emulsify. Then, a cream was prepared and the following tests were conducted.

[0013]

[Table 1]

<Anti-inflammatory Test: Carrageenin Paw Edema Inhibition Test> Wistar rats weighing 110 to 130 g were used as one group consisting of 10 rats. The volume of the right hind limb of the rat is measured by a volume differential meter (volume).
The measurement was made by using a differential meter), and the animals were divided into groups so that the average foot volume of each group was almost constant. The sample was rubbed twice on the right hind footpad 2 hours and 1 hour before the injection of the inflammatory agent, and the rubbed site was covered and protected with an adhesive bandage. 0.1 ml of a 1% carrageenin suspension as an inflammatory agent was subcutaneously injected into the footpad. The volume of the right hind limb was measured hourly for up to 5 hours after injection of the inflammatory agent, and the edema rate and the inhibition rate were calculated from the paw volume before injection of the inflammatory agent based on the following formula.

[0015]

(Equation 1)

The test results are shown in Table 2. From these results, it was confirmed that bufexamac and crotamiton alone have a weak effect of suppressing edema due to carrageenin inflammation in rats, and that the effect of suppressing caffeine only when bufexamac is combined with crotamiton is strong. It was This potentiating effect is considered to be because the transdermal absorbability of bufexamac was improved by combining bufexamac and crotamiton.

[0017]

[Table 2]

<Antipruritic test> Five healthy persons were selected and tested using freshly grated yam as an itching agent.
That is, about 30 minutes before rubbing the pruritic agent, about 0.2 g of the sample had a diameter of about 4
It was applied twice in a range of cm. After 30 minutes, the sample was thoroughly wiped with alcohol cotton to dry the skin, and then 0.5 g of freshly grated yam as an itch was applied and itched. Immediately after itching, the degree of itching was evaluated according to the criteria in Table 3 every 20 seconds until the itching disappeared, and the total score was taken as the result. As a comparative control, the test was started at the beginning of the test after it was confirmed that very strong itching was felt when the same pruritic agent was rubbed without treatment. Here, the result is given every 20 seconds, and is scored until it reaches 0, and this is accumulated. The control becomes 0 after 10 minutes, and the total score (cumulative score) is about 75. Met. This test was repeated 5 times, and this average was used as the test result.

[0019]

[Table 3] The test results are shown in Table 4. Although the bufexamac plain preparation had no antipruritic effect at all, the antipruritic effect was confirmed to be high in the product of the present invention which is a combination drug with crotamiton.

[0020]

[Table 4]

From the results of the above anti-inflammatory test and antipruritic test,
It was found that the combination of bufexamac and crotamiton is a useful therapeutic agent for symptoms such as inflammation and pruritus that are peculiar to skin diseases such as atopic dermatitis.

Example 3 Emulsion A (oil phase portion) Bufexamac 2.5 wt% crotamiton 7.5 sorbitan monostearate 3.0 POE (20) sorbitan monostearate 4.0 octyldodecanol 1. 0 diisopropyl adipate 1.0 soybean lecithin 1.0 B (water phase part) 10.0 1,3-butylene glycol 0.2 methylparaben 0.2 carboxyvinyl polymer 0.2 potassium hydroxide proper amount purified water residual amount total 100 0.0 wt% The oil phase portion of A heated to 60 ° C. is added to the water phase portion of B similarly heated to 60 ° C., the mixture is emulsified and cooled, and then neutralized with potassium hydroxide to obtain an emulsion. The product of the present invention is used as an emulsion when the affected area is wide.

Example 4 Oil Ointment Bufexamac 5.0 wt% Crotamiton 15.0 Octyldodecanol 5.0 Glycerin monostearate 2.0 Plastibase Total residual amount 100.0 wt% Bufexamac, crotamiton, Octyldodecanol and glycerin monostearate are dissolved by heating at 60 ° C. and kneaded with plastibase to prepare an oily ointment.
The product of the present invention is used when the skin is extremely dry such as atopic dermatitis and dry skin disease.

Example 5 Gel Ointment Bufexamac 2.0 wt% crotamiton 10.0 l-menthol 3.0 dibucaine hydrochloride 0.5 POE (20) cetyl ether 3.0 ethanol 35.0 1,3- Butylene glycol 25.0 Carboxyvinyl polymer 1.5 Hydroxypropyl cellulose 0.1 Purified water Remaining amount of sodium hydroxide 0.2 Total 100.0 wt% After dissolving each of them, neutralizing with sodium hydroxide,
Prepare a gel ointment. The product of the present invention is used for skin diseases that require rapid action against itching such as insect bites.

[0025]

INDUSTRIAL APPLICABILITY According to the present invention, the combined use of bufexamac and crotamiton enhances the anti-inflammatory effect of bufexamac and imparts an antipruritic effect, thus atopic dermatitis and dryness. It is possible to provide an optimal drug as a therapeutic agent for a skin disease requiring anti-inflammatory action and antipruritic action such as dermatosis.

Claims (1)

[Claims] 1. A therapeutic agent for skin diseases, which comprises bufexamac and crotamiton.