JPH04149132A - Aqueous solution of danazol - Google Patents

Abstract

PURPOSE:To obtain an aqueous solution of danazol stably storable over a long period and suitable for external preparation or injection by dispersing danazol in an aqueous solution containing a nonionic surfactant and a water-soluble polymer, solubilizing the compound and adding an isotonizing agent, a preservative, etc., to the solution. CONSTITUTION:The objective aqueous solution contains danazol (17alpha-pregna-2,4- dien-20-yno[2,3-alpha]isoxazol-17-ol) as an active component. The solution can be produced by dispersing and solubilizing danazol in an aqueous solution containing a nonionic surfactant and a water-soluble polymer, adding an isotonizing agent, a preservative, etc., to the solution and forming in the form of external preparation or injection. Since danazol is used in the form of aqueous solution, it is rapidly absorbed in the body. Danazol is effective for suppressing the secretion of FSH and LH by antigonadotropic action and free from sex hormonal action and, accordingly, it can be used as a therapeuticagent of uterine endometrium diseases.

Description

[Detailed description of the invention] <A) Industrial application field The present invention relates to an aqueous solution of danazol.

(B) Conventional technology Danazol has anti-conadotrobin effect that causes F S
It is a compound used in the treatment of endometriosis because it suppresses the secretion of H and L)I but does not have sex hormone effects. Due to the excellent effects of danazol, its use is increasing year by year.9 Danazol is currently commercially available in the form of hard capsules, and is administered at a dose of 400 mg per day.

The reason why the daily dose of danazol is so high is because danazol is poorly soluble in water, so the danazol contained in the preparation is absorbed into the gastrointestinal tract (it does not migrate and is excreted from the body before being absorbed). In order to solve these problems, for example, Japanese Patent Application Laid-open No. 1613/1983 has proposed finely pulverizing danazol and dispersing the particles into water or other water-soluble polymers, such as A preparation has been proposed in which the compounds are bonded together using polyhinylpyrrolidone to form a heath-like structure. However, it is difficult to improve the solubility of danazol or to form it into an aqueous solution using water droplets.

Another method aimed at improving the absorption of the human body is to improve the absorption of nifedipine, which is a compound in a synergic solution. In addition, Japanese Patent Publication No. 61-40647 describes a preparation consisting of a specific combination of It is reported that a highly stable and clear solution was obtained by dissolving danazol in an aqueous solution by blending 1 to 50% by weight of a danazol agent and 45 to 98.5% by weight of a polyhydric alcohol.

However, these techniques are primarily aimed at improving dissolution from the preparation and absorption into the body from the gastrointestinal tract. This indicates that when danazol is dissolved, it is absorbed more rapidly. Therefore, the present inventors made extensive studies to obtain an aqueous solution of danazol, and after dispersing a nonionic surfactant and a water-soluble polymer in a water-soluble aqueous solution, the old product was By dissolving and stirring, it was possible to obtain a long-term stable danazol aqueous solution.

Examples are shown below. Example 1 Danazol buffer (pH 7, 8) Polyvinylpyrrolidone-80 g 00 ml Q g ml After dissolving the solution by heating at 80° for 30 minutes,
The mixture was cooled to room temperature, and water was added to make a total volume of 1000 ml to obtain a transparent Danasol O, i'o aqueous solution.

Example 2 Danazol buffer (pi-(7,S) polyhinyl alcohol soybean 20 g 00 ml 0 g 5 ml After dissolving the solution by heating at 80° for an hour,
Cool to room temperature, add water to 10100O, and clear danazol 0.1°. An aqueous solution was obtained.

Solid color M3 Danazol buffer < T) tI2. , 0) Polyvinylpyrrolidone noine 80 Henzalkonium chloride g 700rri10 g 5ml1 0.1g After heating and dissolving the liquid with the above composition at 80° for 1 hour, it was cooled to room temperature, water was added to make it 10100O, and it became transparent. 0.1°. An aqueous solution was obtained.

Special 1〒Minobu Hiroshi Trading Co., Ltd.

Claims (2)

[Claims] (1) 17α-pregnar 2,4 diene-20-ino[
An aqueous solution containing 2,3-α]isoxazol-17ol (hereinafter referred to as danazol) as an active ingredient. (2) After dispersing and solubilizing danazol in an aqueous solution containing a nonionic surfactant and a water-soluble polymer,
Danazol aqueous solution prepared as external preparations and injections by adding tonicity agents, preservatives, etc.