重组人干扰素β-1a注射液的安全药理学研究  

Safety pharmacology study of recombinant human interferon β-1a injection

作　　者：钟飞[1,2] 胡雷 刘艳菊[1] 张彩霞 徐德璐[1] 葛鹏[1] 兰天龙 周博宇[1] ZHONG Fei1, 3, HU Lei1, 3, LIU Yanju1, ZHANG Caixia2, XU Delu1, GE Peng1, LAN Tianlong1, ZHOU Boyu1(1. Tianjin Institute of Pharmaceutical Research New Drug Evaluation Co. Ltd, Tianjin 300301, China 2. Tianjin Institute of Pharmaceutical Research Co. Ltd, Tianjin 300193, China 3. Tianjin Engineering Research Center of Drug Preclinical Assessment Technology, Tianjin 300301, Chin)

机构地区：[1]天津药物研究院新药评价有限公司,天津300301 [2]天津市新药非临床评价技术工程中心,天津300301 [3]天津药物研究院,天津300193

出　　处：《药物评价研究》2018年第2期223-229,共7页Drug Evaluation Research

基　　金：国家科技重大新药创制项目(2015ZX09501004);天津市科技计划项目(16PTGCCX00090)

摘　　要：目的研究重组人干扰素β-1a注射液对实验动物中枢神经系统、呼吸系统、心血管系统以及消化系统的影响,观察药物潜在的对生理功能的不良影响,为临床实验提供依据及参考。方法小鼠单次sc重组人干扰素β-1a注射液5.5、22.0、88.0μg/kg,观察小鼠自主活动,进行平衡协调能力和协同睡眠实验,研究药物对动物中枢神经系统的影响;食蟹猴单次sc重组人干扰素β-1a注射液1、4、16μg/kg,观察食蟹猴的心电、血压、呼吸频率、呼吸幅度,研究药物对动物呼吸系统和心血管系统的影响;小鼠单次sc重组人干扰素β-1a注射液5.5、22.0、88.0μg/kg,进行胃肠推进实验,研究药物对胃肠消化系统的影响。结果小鼠单次sc重组人干扰素β-1a注射液,5.5、22.0、88.0μg/kg剂量组动物自主活动、平衡运动能力未见明显变化、未见与阈下剂量戊巴比妥钠协同睡眠作用,且未见胃肠推进的明显变化;食蟹猴单次sc重组人干扰素β-1a注射液,1、4、16μg/kg剂量组动物未见明显剂量或时效相关性的心血管、呼吸系统影响。结论重组人干扰素β-1a注射液对实验动物的中枢神经系统、呼吸系统、心血管系统及消化系统均未见明显药物影响。Objective To research the drug effects on laboratory animals＇ central nervous system,respiratory system,cardiovascular system and digestive system of recombinant human interferon β-1 a injection under the certain dosages thereby observing the potential adverse effects on physiological functions and providing basis and reference for clinical experiment.Methods The mice received a single dose of 5.5,22.0,and 88.0 μg/kg of recombinant human interferon β-1 a injection by sc injection and the effects on central nervous system were studied by observing the autonomic activity of mice,carrying out balance and coordination ability test and coordinating sleep experiments.The cynomolgus monkeys received a single dose of 1,4 and 16 μg/kg of recombinant human interferon β-1 a injection by sc injection and the effects on respiratory system and cardiovascular system were observed.The mice received a single dose of 5.5,22.0,and 88.0 μg/kg of recombinant human interferon β-1 a injection by sc injection and the effects on digestive system were observed through gastrointestinal propulsion experiment.Results No significant changes in spontaneous activities of mice after a single dose of 5.5,22.0 and 88.0 μg/kg of recombinant human interferon β-1 a injection administration were found.The balance and exercise abilities of mice showed no impacts.No function together with subthreshold dose of sodium pentobarbital to cause mice sleep were found.No significant changes in respiratory and cardiovascular system of cynomolgus monkeys after a single dose of 1,4 and 16 μg/kg of recombinant human interferon β-1 a injection by hypodermic injection were found.No significant changes in gastrointestinal propulsive effect of mice after a single dose of 5.5？22？88 μg/kg of recombinant human interferon β-1 a injection by hypodermic injection were found.Conclusions Recombinant human interferon β-1 a injection showed no significant influences on laboratory animals＇ central nervous system,respiratory system,cardiovascular system and d

关 键 词：重组人干扰素β-1a注射液 中枢神经系统 心血管系统 呼吸系统 消化系统 安全药理学 

分 类 号：R994[医药卫生—毒理学]