Hydroxyfasudil-containing pharmaceutical composition for injection

Abstract

The invention relates to a prescription of a hydroxyfasudil-containing pharmaceutical composition for injection. The prescription of the hydroxyfasudil-containing pharmaceutical composition for injection is characterized by comprising pharmaceutically effective quantity of hydroxyfasudil and a proper amount of pharmaceutical auxiliary materials, wherein the pharmaceutical auxiliary materials are citric acid and sodium citrate, and the pH value of injection is 5.0-7.0. The invention also discloses a preparation method of the hydroxyfasudil-containing pharmaceutical composition for the injection. The preparation method of the hydroxyfasudil-containing pharmaceutical composition for the injection comprises the following steps: firstly adding hydroxyfasudil and citric acid according to the prescription in an activated carbon adsorption process, lowering the temperature to 10-20 DEG C, adding activated carbon for adsorbing, then adding sodium citrate according to the prescription, raising the temperature to 35-50 DEG C, further adsorbing with the activated carbon, filtering and decarbonising. The prescription of the hydroxyfasudil injection is simple, photostability is strong, and quality is stable; meanwhile, a technological process is simple, so that the prescription of the hydroxyfasudil-containing pharmaceutical composition for injection is applicable to industrial 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, 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, due to its remarkable curative effect and small side effects, it has become the first choice for clinical treatment of such diseases. The prescription of the original Fasudil hydrochloride injection contains 30g of Fasudil hydrochloride, 16g of sodium chloride, the pH is adjusted to 5.9-6.1, and water for injection is added to 2000ml. However, it is reported in 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 The total impurity content was higher than 1% under the condition of 4500LX±500Lx light for 10 days, and the impurity content exceeded the national drug standard WS1-(X-110)-2006Z on the total The content must not exceed the requirement of 1%, and the stability of the injection is poor; and the cysteine ​​hydrochloride used in the patent CN 103222953 A background technology reports that it has a peculiar smell and has an anti-oxidant effect. Salts can be formed from strong acids and strong bases, 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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