JPS58150509A - Remedy for trichophytosis - Google Patents

Abstract

PURPOSE:A remedy for trichophytosis that is made by dissolving tolnaftate and urea in a solvent consisting of three components, methyl ethyl ketone, water and alcohol at a specific ratio, thus showing improved storage stability and penetration of the remedy into horny layer. CONSTITUTION:2pts.wt. of tolnaftate are used as an active ingredient, and they are combined with 1-10pts.wt. of urea to increase the curing effect for trichophytosis. Further, they are dissolved in a solvent consisting of 50-85pts.wt. of methyl ethyl ketone, 5-20pts.wt. of water and 5-30pts.wt. of ethanol to give the objective remedy for trichophytosis with improved storage stability and penetration of tolnaftate into horny layer. When necessary, chlorhexidine digulconate or other fungicides and lactic acid or other pH stabilizers may be added in appropriate amounts.

Description

[Detailed description of the invention] TECHNICAL FIELD The present invention relates to a therapeutic agent for leukemia.

Skin diseases caused by leprosy fungi include jock itch, ringworm, etc., and topical therapy in which various anti-leucophilic agents are applied to the affected area is often used to treat these leukemia. Complete treatment is often difficult. This is due to the fact that normal antibacterial agents are unable to penetrate because white bacterium generally grows inside the stratum corneum, which covers the outermost layer of the skin. Therefore, the results of topical therapy are This is because it is often influenced by the thickness of the stratum corneum in the affected area and the penetration power of the drug into the stratum corneum rather than the antibacterial power itself.

The present inventors have been researching therapeutic agents for leukemia, but
Among the many anti-leukosis bacteria, it has been found that tolnaftate, in particular, can significantly enhance its therapeutic effect on leukemia by incorporating urea into it.

However, since tolnaftate and urea are dissolved in different solvents, it is difficult to obtain a solution in which both are dissolved, and even solutions obtained by chance have poor storage stability, resulting in phase separation and dissolved components. However, tolnaftate's ability to penetrate into the stratum corneum was poor.

As a result of various studies, the present inventors have determined that tolnaftate and urea can be converted into methyl ether ketone. By dissolving the three components of water and alcohol in a specific ratio in a solvent, we succeeded in obtaining a liquid preparation with excellent storage stability and drug penetration into the stratum corneum, and completed the present invention.

The object of the present invention contains 2 parts by weight of tolnaftate as an active ingredient, and 50 to 8 parts by weight of this together with 1 to 10 parts by weight of urea.
5 parts by weight of methyl ethyl ketone.

It is a therapeutic agent for leukemia, which is dissolved in a solvent consisting of 5 to 20 parts by weight of water and 5 to 30 parts by weight of ethanol.

In the present invention, appropriate amounts of a bactericide such as chlorhexidine digluconate and a pH stabilizer such as lactic acid may be added as necessary.

The object of the present invention can be produced as follows.

First, a solution A is prepared by dissolving a methyl ethyl ketone dissolved component such as tolnaftate in methyl ethyl ketone.

Next, solution B is prepared by dissolving water-soluble components such as urea, chlorhexidine digluconate, and lactic acid in water, and then adding ethanol thereto.

Finally, the object of the present invention can be produced by adding solution B little by little to solution A while stirring.

The mixture of tolnaftate and urea does not dissolve in methyl ethyl ketone, alcohol, or water individually, and it does not dissolve in a mixed solvent of these five components other than the above-mentioned specific ratio, or the stability of the resulting solution is low. not good.

The object of the present invention is that the solvent is a mixed solvent of these three components in a specific ratio, and the mixture of tolnaftate and urea is in a completely dissolved solution state, which improves storage stability and the incorporation of tolnaftate into the stratum corneum. It has excellent penetrating power, making it useful as a treatment for baldness.

The present invention will be specifically explained below with reference to test examples that clarify various properties of the target product of the present invention and examples that show manufacturing examples of the target product of the present invention.

Test Example 1 Example 1 below. Liquids 1, 2, and 3 prepared in Examples 2 and 3 were stored at room temperature for 90 days, and the condition of the liquids was examined, but no abnormality was observed in any of them.

Test Example 2 The liquid preparation prepared in Example 1 described later was used as the test sample.Urea, water, and lactic acid were removed from the sample components, and a liquid preparation prepared by adding 2% by weight of salicylic acid to the total station instead was used as Control 1. Urea from the ingredients.

Control 2 was a solution prepared by removing water and lactic acid.

The abdomen of the guinea pig was dehaired, the dehaired area was wiped with 70% ethanol, and after about 20 minutes, a cylindrical glass cell with an inner diameter of 15 Crn was fixed to the dehaired area with an adhesive.

Into this glass cell, 90 µt of specimen and control were separately injected and made homogeneous, left as it was at room temperature for 3 hours, unabsorbed drug was recovered with chloroform, and the skin at the application site was excised, and the excised skin remained. After homogenization, the amount of tolnaftate absorbed into the skin was measured using liquid chromatography.

The results are shown in Table 4.

Table 4 Test example of tolnaftate absorbed into the skin (μ2) 3 Hair was removed from the back of a guinea pig in a circular shape with a diameter of 4 mm, a slight scratch was made evenly with sandpaper, and the white bacteria was removed with physiological saline. The suspension was applied with a small brush for inoculation.

From the 41st day after inoculation to 98 days after inoculation, the liquid preparation prepared in Example 1.2.3 (specimen 1 and 2, respectively) was administered 11 times a day every day.
．． 5. ) and Control 1.2 prepared in Test Example 2 were applied separately, and after applying the solution, 9.
On the next day, all animals were sacrificed, the lesions were excised, and tissue pieces were collected from 8 locations uniformly from each lesion. These were cultured on Sabouraud's agar medium to determine the presence or absence of bacteria. The treatment effect was investigated.

The results are shown in Table 5.

Table 5: Example 1 of therapeutic effect on albinism 1 Solution A was prepared by dissolving tolnaftate 2 in 50V of methyl ethyl ketone.

Separately, evening Lorheki 7 gin digluconate 0.02P.

Urea 5. Of and lactic acid 052 are dissolved in water 101,
Solution B was prepared by adding ethanol 109 to this.

Solution B was added to solution A while stirring, and both solutions were thoroughly mixed. Then, methyl ethyl ketone was further added to make the total amount 100 m/ml, thereby obtaining a therapeutic agent for leukemia.

Example 2 Tornafuchi) 2.09
Chlorhexidine digluconate [1,02f urine
Element 1
0. Of lactic acid
0.72 water
20.0f ethanol
Make the total amount to 100- with 15.0f methyl ethyl ketone.

According to Example 1, a therapeutic agent for leukemia with the above composition was obtained.

Example 3 Tolnaftate 20? Urea 1.09 Lactic acid 0.52 Water 5. Of etal/-le 10. Of methyl ethyl ketone to bring the total amount to 1 nO-.

According to Example 1, a therapeutic agent for white cap disease having the above composition was obtained. Patent applicant: Taisho Pharmaceutical Co., Ltd. Agent Patent Attorney Kitakawa Tomizo Continued from page 1 0 shots clear person Takashi Shuto 3-24-1 Takada, Toshima-ku, Tokyo Inside Taisho Pharmaceutical Co., Ltd. Founder: Tadao Maruta 3-24-1 Takada, Toshima-ku, Tokyo Inside Taisho Pharmaceutical Co., Ltd.

Claims (1)

[Claims] (l) A solvent consisting of 2 parts by weight of tolnaftate as an active ingredient, 1 to 10 parts by weight of urea, 50 to 85 parts by weight of methyl ethyl ketone, 5 to 20 parts by weight of water, and 5 to 30 parts by weight of ethanol. A therapeutic agent for albinism dissolved in.