幼龄大鼠给予芩暴红止咳口服液的非临床安全评价  

Non-clinical Safety Evaluation of Qinbaohong Antitussive Oral Liquid in Young Rats

作　　者：苏萍[1] 杨依霏[1] 张东[1] 何隽 张海静 王丽芳[1] 夏冰 赵春晖 宫平 刘婷[1] SU Ping;YANG Yi-fei;ZHANG Dong;HE Jun;ZHANG Hai-jing;WANG Li-fang;XIA Bing;ZHAO Chun-hui;GONG Ping;LIU Ting(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,北京100700

出　　处：《中国现代中药》2023年第12期2499-2511,共13页Modern Chinese Medicine

基　　金：中国中医科学院科技创新工程项目(CI2021A04807)0108425。

摘　　要：目的:从多指标观察幼龄大鼠连续灌胃给予芩暴红止咳口服液13周可能引起的毒性反应和毒性靶器官,为临床应用提供参考。方法:120只雌、雄大鼠1:1同笼交配,记录仔鼠出生日期,至仔鼠出生20 d,取同日出生的仔鼠,按体质量随机分为对照组和芩暴红止咳口服液12.3、24.6、49.2 g·kg-1(以生药量计)组,每组40只,雌雄各半。仔鼠出生21 d开始,给予相应剂量的芩暴红止咳口服液,对照组给予超纯水,给药体积为10 mL·kg-1,每天给药2次,连续给药13周。观察动物的一般症状,进行体质量、摄食量、身体发育指标和生殖器官发育检查。分别于给药4周、13周和恢复期处死大鼠,检测相关指标,包括神经行为学、骨密度、免疫、眼科、尿常规、血液学指标、血液生化学指标、脏器系数和组织病理学。结果:与对照组比较,芩暴红止咳口服液低、中、高剂量组大鼠感觉功能、运动协调能力、学习记忆能力、骨密度、免疫功能、生殖器官发育及功能、眼科、尿常规、血液学指标、血液生化学指标、脏器系数和组织病理学均未见明显异常。结论:以多时间点、多指标体系可对中药复方制剂芩暴红止咳口服液进行较为全面的非临床安全评价,高剂量暴露量可达幼儿临床剂量的31.5倍;重复给药13周,未见明显毒性反应。Objective:To observe the possible toxic reactions and toxic target organs caused by continuous gavage of Qinbaohong Antitussive Oral Liquid(QAOL)in young rats for 13 weeks from multiple indexes,to provide reference for its clinical application.Methods:A total of 120 male and female rats were mated in the same cage at the ratio of 1:1,and the birth date of newborn rats was recorded until the 20th day of birth.The newborn rats born on the same day were randomly divided into control group and QAOL 12.3,24.6 and 49.2 g·kg–1(crude drug)groups according to body weight,with 40 in each group and half male and half female.From the 21st day of birth,the rats were give QAOL of corresponding doses,while the control group was given ultra-pure water,with the dosage volume of 10 mL·kg–1,twice a day for 13 consecutive weeks.The general symptoms of the rats were observed,and body mass,food intake,body development index and reproductive organ development were examined.The rats were sacrificed at 4 weeks of administration,13 weeks of administration and recovery period,and the relevant indexes were detected,including neuroethology,bone mineral density,immunity,ophthalmic examination,urine routine,hematological indexes,blood biochemical indexes,organ coefficient and histopathology.Results:Compared with the control group,QAOL groups presented no significant abnormality in sensory function,motor coordination,learning and memory ability,bone mineral density,immune function,reproductive organ development and function,ophthalmic examination,urine routine,hematological index,blood biochemical index,organ coefficient and histopathology.Conclusion:The non-clinical safety of QAOL can be comprehensively evaluated by multi-time point and multi-index system,and the high dose exposure can reach 31.5 times of the clinical dose of infants.No obvious toxicity was observed after repeated administration for 13 weeks.

关 键 词：芩暴红止咳口服液 非临床安全评价 幼龄大鼠 满山红 暴马子皮 黄芩 

分 类 号：R285.5[医药卫生—中药学]