冠心宁注射液安全性再评价研究(I)

Re-evaluation of the security of Guanxinning Injection (I)

目的为做好冠心宁注射液安全性再评价工作提供数据参考。方法采用不同给药剂量,按《中国药典》2010年版一部附录方法进行异常毒性检查、过敏反应检查及降压物质检查,根据样品注射后动物反应情况,进行分级评价。结果异常毒性检查:不同厂家的样品原液异常毒性检查结果差异明显,A、D及F3个厂家的产品异常毒性较小,均未出现动物死亡,其中A与F两个厂家均只有一批样品得3分;B厂的产品异常毒性变化较大,13批样品中,除一批样品未见明显毒性反应外,有8批样品出现动物死亡,占总数的53.3%;C和E厂的产品表现出较大的异常毒性,得分在2～5分,D厂产品最稳定,13批样品得分集中分布在2～3分,没有出现动物死亡情况;选用样品1︰2的稀释液,71批样品中,仅有1批出现动物死亡;不同来源、不同品种动物反应结果基本一致。降压物质检查:冠心宁注射液有一定的降压作用,注射0.2mL/kg样品原液,降压幅度大于组胺对照(0.1μg/kg)组,选用样品1︰3的稀释液,71批样品中,仅B厂有4批样品不合格,经换猫再试,有1批样品仍不合格,3批合格。过敏反应检查:取不同厂家样品24批进行过敏反应检查,结果均未出现明显的过敏反应。结论不同厂家、同一厂家不同生产批号的冠心宁注射液异常毒性、降压物质检查结果存在差异,可增加异常毒性、降压物质检查来控制其质量。

Objective To provide the data for re-evaluation on the security of Guanxinning Injection. Methods Testing for abnormal toxicity, allergen, and depressor substances was performed in different doses, according to the methods in the appendix of Chinese Pharmacopoeia 2010; And the grading evaluation was recorded by the animals’ reactions after sample injection. Results In the examination of abnormal toxicity, toxicity of samples from different manufacturers varied widely. The samples from A, D, and F manufacturers had less toxic, in which no animal was dead. Among them A and F only had one batch with getting three points; Sample from B manufacturer had unstable and abnormal toxicity, and animal deaths occurred in eight among 13 batches of samples except that one batch had no significant toxicity, accounting for 53.3%; Samples from C and E manufacturers showed a greater abnormal toxicity, scored two to five points; Sample from D manufacturer was the most stable. Scoring between two and three points was concentrated among 13 batches, there was no animal death; Among 71 batches of samples dilution in 1 ： 2 was selected, animal deaths occurred in only one batch; The results are basically the same from different sources and varieties of animals. In buck physical examination, Guanxinning Injection has antihypertensive effect and samples in a dose of 0.2 mL/kg had more significant effect on controlling blood pressure than histamine （0.1 μg/kg）. While the dilution in 1 ： 3, only four batches of B manufacturer have failed, and the experiments were repeated using cats, the results were still unsatisfactory, among which one batch failed and three batches were qualified; In allergy check, 24 batches of samples from different manufacturers had no obvious abnormal reaction. Conclusion There is difference of abnormal toxicity test and buck physical examination among Guanxinning Injections produced by different manufacturers. It suggests that abnormal toxicity test and buck physical examination can be used to control the quality.