A pharmaceutical composition containing fasudil hydrochloride for injection

Abstract

The invention relates to a prescription of a pharmaceutical composition containing fasudil hydrochloride for injection, which is characterized in that it consists of a pharmaceutically effective amount of fasudil hydrochloride and an appropriate amount of pharmaceutical excipients, wherein the pharmaceutical excipients are lemon acid and sodium citrate, the pH value of the injection is in the range of 5.0 to 7.0. The invention also discloses the preparation method of the injection prescription: in the activated carbon adsorption process, first add the prescribed amount of fasudil hydrochloride and citric acid, lower the temperature to 10-20 degrees, add activated carbon for adsorption, and then add the prescribed amount of lemon Sodium acid, raise the temperature to 35-50 degrees, the activated carbon continues to adsorb, and decarburizes by filtration. The fasudil hydrochloride injection provided by the invention has the advantages of simple prescription, strong photostability, stable quality, simple process flow, and is suitable for industrialized production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, in particular to a pharmaceutical composition containing fasudil hydrochloride for injection and a preparation method thereof. Background technique [0002] Fasudil hydrochloride is a new type of RhO kinase inhibitor. It was jointly developed by Asahi Kasei Pharmaceutical Co., Ltd. and the Pharmacology Laboratory of Nagoya University. It was officially approved for clinical use in Japan in 1995 for the prevention and treatment of chronic ischemic vasospasm. . Since the product has been on the market for more than ten years, it has become the first choice for clinical treatment of such diseases due to its remarkable curative effect and small side effects. The prescription of the original fasudil hydrochloride injection contains 30 g of fasudil hydrochloride, 16 g of sodium chloride, the pH is adjusted to 5.9 to 6.1, and the water for injection is added to 2000 ml. However, the Chinese ...

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Problems solved by technology

Chinese patent CN104069063A manual comparative example 1 also discloses that Fasudil hydrochloride injection prepared according to the original research prescription increases nearly 5 times in related substances after 6 months of accelerated test, and the stability of the injection is not good

Such as CN102266343A discloses a kind of fasudil hydrochloride pharmaceutical composition for injection, contains fasudil hydrochloride, sodium chloride in the injection, and adds antioxidant cysteine ​​hydrochloride, but the applicant finds experimentally, according to this The injection prepared by the prescription of Patent Example 1 had a total impurity content of 0.07% at day 0, but the total impurity content was 0.78% in the accelerated test at 40°C and 75% RH for 6 months, and the impurity content increased by more than ten times; and in Placed under the condition of light 4500LX±500Lx for 10 days, the total impurity content is higher than 1%, and the impurity content exceeds the national drug standard WS 1 -(X-110)-2006Z requires that the total impurity content of Fasudil hydrochloride injection should not exceed 1%, and the stability of the injection is poor; and the patent CN103222953 A background technology reports that the cysteine ​​hydrochloride used in its prescription has a peculiar smell , has anti-oxidation effect, can be oxidized and destroyed when encountering oxidizing agents, and can form salt when encountering strong acid and strong alkali, which will have a certain impact on the quality of the preparation

Chinese patent CN103040738A discloses a pharmaceutical composition containing fasudil hydrochloride, which includes fasudil hydrochloride, sodium dihydrogen phosphate, dextran 40, methionine and water for injection. We prepared injections according to its formula 1 and accelerated the test 6 In July, it was found that the total impurity content was still higher than 0.5%. Although the stability had been improved to a certain extent, its prescription was complicated, and dextran was a polymer, which was prone to polymerization to form polymers, causing the solution to change color and bringing safety hazards to the medication.

[0005] Yet, the general existence of the fasudil hydrochloride injection provided by the prior art is poor in photostability, the impurity content is high, and the problem of long-term storage stability of the product is poor; Reducing the degradation of fasudil hydrochloride by means of pH value will lead to increased stimulation of blood vessels by the injection, poor drug compliance, and poor safety defects

In addition, currently commercially available fasudil hydrochloride injections all use brown containers as inner packaging materials. Although the photostability of injections has been improved to a certain extent, the photostability of fasudil hydrochloride injections has not been fundamentally solved. problems, and compared with ordinary colorless transparent containers, brown containers have the problems of high cost and lower quality during production (difficult for light inspection)

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