磷酸川芎嗪注射剂的溶血试验及诱发类过敏反应的机制  

Hemolytic tests and the mechanisms of anaphylactoid reactions induced by Ligustrazine phosphate injection

作　　者：杨海燕[1] 周继春[1] 张婷婷[1] 张军霞[1] 林红军[1] 郭兴辉[1] YANG Haiyan;ZHOU Jichun;ZHANG Tingting;ZHANG Junxia;LIN Hongjun;GUO Xinghui(Henan Provincial Insititute of Food and Drug Control,Zhengzhou,Henan,450003 P.R.China)

机构地区：[1]河南省食品药品检验所,河南郑州450003

出　　处：《华西药学杂志》2020年第4期397-401,共5页West China Journal of Pharmaceutical Sciences

摘　　要：目的研究磷酸川芎嗪注射剂的溶血试验及诱发类过敏反应的机制。方法分别用光度法及目视法比较两种溶剂中,磷酸川芎嗪引起的溶血反应,采用豚鼠耳静脉注射法对9家生产企业不同规格的21批次样品分别进行了类过敏试验,用ELISA法测定血清中组胺(His)、类胰蛋白酶(TPS)、β-己糖苷酶(β-Hex)、血清免疫球蛋白E(Ig E)的含量。结果以0.9%氯化钠注射液和5%葡萄糖注射液为稀释液的供试品溶液达到0.2 mg·m L^-1临床配伍浓度时,目视法观察3 h无溶血现象;以0.9%氯化钠注射液和5%葡萄糖注射液为稀释液的供试品溶液浓度达到5 mg·m L^-1时,目视法观察3 h,8家企业18批产品均发生溶血现象。用光度法测定溶血率时,以5%葡萄糖注射液为稀释液的供试品溶液浓度达0.2 mg·m L^-1时,8家企业产品溶血率均小于5%。与阴性对照组比较,注射用磷酸川芎嗪注射后均引起血清中组胺的水平增高,10批样品血清中组胺的水平显著增高;12批注射用磷酸川芎嗪均可使血清中类胰蛋白酶的含量显著增加;16批注射用磷酸川芎嗪使血清中β-己糖苷酶的释放显著增加;14批注射用磷酸川芎嗪可引起血清中Ig E的含量显著性增加。结论注射用磷酸川芎嗪存在溶血的安全隐患,临床配伍时,选用5%葡萄糖注射液为稀释液可能会更安全。注射用磷酸川芎嗪可引发类过敏反应,其原理可能与药物引起补体系统激活,直接刺激肥大细胞脱颗粒释放组胺、类胰蛋白酶和β-己糖苷酶有关。OBJECTIVE To study the hemolytic test of Ligustrazine phosphate injection(LPJ),and to research the mechanisms of the anaphylactoid reactions induced by LPJ.METHODS The results of hemolytic test in two solvents were compared by spectrophotometry and visual method.Anaphylactoid reactions on guinea pigs were observed by injecting LPJ into auricular vein.The concentrations of histamin(His),tryptase(TPS),beta-hexosidase(β-Hex)and serum immunoglobulin(Ig E)in plasma were detected by ELISA.RESULTS When LPJ were diluted respectively in 0.9%sodium chloride injection and 5%glucose injection,at the concentration of 0.2 mg·m L^-1,hemolysis was not observed by visual method in 3 hours.At the concentration of 5 mg·m L^-1,hemolysis was observed by visual method in 3 hours.Hemolyticrate of samples from 8 companies were below 5%when diluted in 5%glucose injection to the concentration of 0.2 mg·m L^-1 by spectrophotometry method.After intravenous injection,the level of histamin of 10 batch samples increased significantly,the level of tryptase of 12 batch samples increased significantly,the level of beta-hexosidase of 16 batch samples increased significantly,the level of Ig E in plasma of 14 batch samples increased significantly compared with control.CONCLUSION Potential safety risks of hemolysis exsits in clinical use of LPJ,but it will be better by using 5%glucose injection as solvent.Anaphylactoid reactions induced by LPJ are asociated with complement system activation and direct stimulation of mast cell degranulation by releasing of histamin,tryptase and beta-hexosidase.

关 键 词：磷酸川芎嗪注射剂 溶血反应 用药安全 类过敏反应 组胺 类胰蛋白酶 β-己糖苷酶 免疫球蛋白E 补体系统激活 

分 类 号：R96[医药卫生—药理学]