醒脑静注射液不良反应临床前相关研究  

Preclinical study on adverse reactions of Xingnaojing injection

作　　者：易艳[1] 李春英[1] 赵雍[1] 潘辰[1] 刘素彦[1] 王连嵋[1] 张宇实[1] 韩佳寅[1] 田婧卓 梁爱华[1] YI Yan;LI Chun-ying;ZHAO Yong;PAN Chen;LIU Su-yan;WANG Lian-mei;ZHANG Yu-shi;HAN Jia-yin;TIAN Jing-zhuo;LIANG Ai-hua(State Key Laboratory of Innovative Natural Medicine and TCM Injections,Key Laboratory of Beijing for Identification and Safety of Chinese Medicine,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中药研究所中药鉴定与安全性检测评估北京市重点实验室创新天然药物与中药注射剂国家重点实验室

出　　处：《中国中药杂志》2018年第13期2789-2795,共7页China Journal of Chinese Materia Medica

基　　金：国家“重大新药创制”科技重大专项(2014ZX09201022,2015ZX09501004);北京市科技计划项目(Z161100004916025,Z151100000115012);中国中医科学院重点领域研究专项(ZZ10-025);中国中医科学院自主选题项目(ZZ0808009,ZXKT15013,ZXKT15031)

摘　　要：该研究首先通过选择不同批号的醒脑静注射液产品进行小鼠类过敏试验,结果在给予临床6.6倍剂量注射液后,临床具有不良反应报告的相应批号注射液可诱发小鼠发生轻微类过敏反应,其余批号则无,初步认为该小鼠模型可以很好地提示醒脑静注射液临床上使用的类过敏风险。另外通过改变部分工艺,制作出高浓度的醒脑静注射液并进行小鼠类过敏试验和豚鼠主动全身过敏试验,结果豚鼠未见明显Ⅰ型过敏样反应发生,而小鼠在给予临床6.6倍剂量注射液后发生轻微类过敏反应,故认为对于敏感或特异质人群（代谢异常）,可能会造成醒脑静注射液进入体内后其中某些化学组分浓度增加,从而会导致其诱发类过敏反应的风险加大。而由于检测模型的限制,目前暂不能排除醒脑静注射液诱发过敏反应的风险。最后,该研究又通过加大醒脑静注射液中冰片和辅料聚山梨酯（吐温）和（或）氯化钠的含量并再进行类过敏检测,结果表明上述3种成分混合后可能会产生新的微量致敏物质并诱发类过敏反应。In this study,different batches of Xingnaojing injection products were first selected for pseudoallergic mice test,and the results showed that after injection of 6. 6-fold clinical dose Xingnaojing injection,the mice showed a slight pseudoallergic reaction,while other mice injected with other batches of injections showed no obvious pseudoallergic reaction. Therefore,it is preliminarily believed that this mice model can effectively indicate the risk of pseudoallergic reactions in the clinical application of Xingnaojing injections. In addition,by changing some of the processes,a high concentration of Xingnaojing injection was prepared for mice pseudoallergic test and guinea pig systemic allergy test. The results showed no significant type Ⅰ allergic reaction in guinea pigs. Mild pseudoallergic reactions occurred in mice after a 6. 6-fold clinical dose injection. Therefore,it is considered that for sensitive or idiosyncratic people,the concentration of certain chemical components in Xingnaojing injection will increase after entering the body,which may increase the risk of pseudoallergic reaction. However,due to the limitations of test models,the risk of Xingnaojing injection to induce allergic reactions cannot be ruled out. Finally,by increasing the content of borneol and Tween and（or） sodium chloride in Xingnnaojing Injection and testing its pseudoallergic reactions,the results showed that the combination of these three ingredients may produce new trace sensitization substance and induce pseudoallergic reactions.

关 键 词：醒脑静注射液 过敏反应 类过敏反应 致敏物质 

分 类 号：R285.6[医药卫生—中药学]