注射用盐酸甲氯芬酯及有关物质的毒性研究  

Study on the toxicity of meclofenac hydrochloride for injection and related substances

作　　者：赵巍[1] 吴兆伟[1] 张喆[1] 胡琴[1] 王琳[1] ZHAO Wei;WU Zhao-wei;ZHANG Zhe;HU Qin;WANG Lin(Beijing Institute for Drug Control,Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine,Beijing 102206,China)

机构地区：[1]北京市药品检验所中药成分分析与生物评价北京市重点实验室,102206

出　　处：《中国医药生物技术》2018年第5期437-441,共5页Chinese Medicinal Biotechnology

摘　　要：目的研究注射用盐酸甲氯芬酯及有关物质的小鼠异常毒性及细胞毒性。方法预实验确定给药剂量,正式实验120只小鼠随机分组(雌雄各半,每组12只),给药后连续观察30 min,记录小鼠异常反应情况。应用小鼠肝脏细胞AML-12观察药物的细胞毒性。结果盐酸甲氯芬酯的杂质根据结构可分为对氯苯氧乙酸类似物和胆碱类。对氯苯氧乙酸类似物具有镇静作用,且安全范围高于盐酸甲氯芬酯,胆碱类杂质具有明显的外周胆碱类反应,具有刺激性毒性。各杂质对注射用盐酸甲氯芬酯的体外细胞毒性基本无影响。结论盐酸甲氯芬酯胆碱类杂质毒性较高,需重点关注。该研究为制定注射用盐酸甲氯芬酯质量标准提供科学依据,提高临床用药的安全性及有效性。Objective To study the abnormal toxicity in mice and cytotoxicity of meclofenac hydrochloride for injection and related substances. Methods In the preliminary experiment to determine the initial dose, the mice were grouped randomly （half male and half female, 12 mice per group） in the formal experiment. The animal reactions were recorded for 30 minutes. The cytotoxicities on mouse liver cells AML- 12 were measured. Results The impurities of meclofenac hydrochloride can be divided into p-chlorophenoxyacetic acid analogues and choline bases according to the structure. The former has a sedative effect and the safety range is higher than that of meclofenac hydrochloride. Choline impurities have obvious peripheral choline response and high toxicity. The impurities had no effect on the in vitro cytotoxicity of meclofenac hydrochloride for injection.Conclusion The toxicity of choline impurities is high and attention must be paid to monitor of the related substances of meclofenac hydrochloride for injection, to improve the safety and effectiveness of clinical medications.

关 键 词：甲氯芬酯 异常毒性 细胞毒性 

分 类 号：R965[医药卫生—药理学]