JPS6121450B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to 1-[1-{3-(4-fluorobesozoyl)propyl}-4-piperidyl]-2,3
This invention relates to a stable injection of dihydrobenzimidazole-2-thione. This compound is known from Japanese Patent Application Laid-Open No. 50-84578 and is useful as a psychoactive agent, but it is extremely difficult to use with water (1
The amount of water required to dissolve g at room temperature is
(2.8×10 ⁵ ml), injections cannot be manufactured without using a suitable solubilizer. Although this compound is easily soluble in chloroform, dimethyl sulfoxide, acetone, etc., it cannot be used in injections due to toxicity, so it is solubilized using organic solvents that can be added to injections, such as glycols such as macrogol. 0.1W/V% even when
To achieve this concentration, more than 60% of glycols must be added, making it unsuitable for actual use. Furthermore, when organic acids such as acetic acid, tartaric acid, and citric acid are used, crystals are precipitated, and in order to obtain a concentration of 0.1 W/V%, the pH must be lowered to a level unsuitable for use as an injection. The following shows the state of crystal precipitation when solutions prepared at a concentration of 0.1 W/V% using various organic acid buffers were stored at 5°C for 6 months.

[Table] In addition, this compound also showed
It did not dissolve at a concentration of 0.1 W/V%. As a result of various studies, the present inventors have completed the present invention by finding that injections of sufficient concentration can be obtained by using a 1/50M to 1/200M lactic acid-sodium lactate buffer as a solubilizing agent. A solution prepared to a concentration of 0.1 W/V% using lactic acid-sodium lactate buffer in the same manner as above was heated at 5°C for 6 hours.
The results after storage for several months are shown below.

[Table] In addition to the base agent and solubilizing agent, saccharides such as saccharide, mannitol, sorbitol, etc. may be added as an isotonizing agent to the injection preparation of this invention. It is also possible to add benzyl alcohol or the like as a soothing agent. To prepare an injection, add a lactic acid-sodium lactate buffer (for example, mix an appropriate amount of 1/100M lactic acid aqueous solution and 1/100M sodium lactate aqueous solution to prepare a buffer with the required pH), a base agent, an isotonic agent, All you have to do is dissolve the soothing agent, etc., but in order to make it easier to dissolve the main agent, first dissolve it in a buffer with a high pH and a high amount of lactic acid, then use sodium lactate or a buffer with a high pH and a high amount of sodium lactate. It is convenient to add liquid to adjust the pH to an appropriate range for injection. Example 1-[1-{3-(4-fluorobenzoyl)
1 g of propyl}-4-piperidyl]-2,3-dydrobenzimidazole-2-thione and 53 g of the tonicity agent D-sorbitol were heated and dissolved in 800 ml of a 1/100M lactic acid-sodium lactate aqueous solution (PH3.3). After returning to room temperature, add 1/100M lactic acid-sodium lactate aqueous solution and adjust the pH to 3.80 to bring the total volume to 1. After filtration in the usual manner, divide into small portions, fill in ampoules and seal, and finally sterilize. An injection was produced.

Claims (1)

[Claims] 1. Lactic acid - 1- containing a sodium lactate buffer solution
[1-{3-(4-fluorobenzoyl)propyl}-4-piperidyl]-2,3-dihydrobenzimidazole-2-thione injection.