十味龙胆花胶囊SD大鼠13周重复给药毒性研究  

Toxicity study of Shiwei Longdanhua capsule to SD rats after repeated administration for 13 weeks

作　　者：康超 李万芳[1,2,3] 李莎莎 牟文波 范维 王应印 田璐 叶向锋 李征军 邱晓军 靳洪涛 KANG Chao;LI Wan-fang;LI Sha-sha;MU Wen-bo;FAN Wei;WANG Ying-yin;TIAN Lu;YE Xiang-feng;LI Zheng-jun;QIU Xiao-jun;JIN Hong-tao(New Drug Safety Evaluation Center,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;NMPA Key Laboratory for Safety Research and Evaluation of Innovative Drug,Beijing 102206,China;Beijing Union-Genius Pharmaceutical Technology Development Co.Ltd,Beijing 100176,China;Tibet Tibetan Medicine Group Co.,Ltd.,Tibet Autonomous Region,Lhasa,Tibet 850000,China)

机构地区：[1]中国医学科学院北京协和医学院药物研究所新药安全评价研究中心,北京100050 [2]NMPA创新药物安全性研究与评价重点实验室,北京102206 [3]北京协和建昊医药技术开发有限责任公司,北京100176 [4]西藏藏药集团股份有限公司,西藏拉萨850000

出　　处：《毒理学杂志》2025年第1期54-59,67,共7页Journal of Toxicology

摘　　要：目的SD大鼠13周重复灌胃十味龙胆花胶囊,观察给药后动物出现的毒性反应及毒性反应的性质和程度,毒性反应的发展和恢复情况;预测其可能对人体产生的不良反应;确定毒性剂量—效应关系;确定毒性作用的靶器官及其损害的可逆性;为临床安全用药的剂量设计和临床毒副反应监测提供参考。方法本次试验设对照组和十味龙胆花胶囊低、中和高剂量组,剂量分别为1、2和4 g/kg·bw。本次试验共使用7~8周龄SD大鼠120只,雌雄各半,使用Provantis系统根据动物体重随机分组,每组雌雄各15只。经口灌胃给药,给药体积10 ml/kg,给药1次/d,连续给药13周。试验期间,每天对动物进行笼旁观察,每周进行临床观察及测定体重、摄食量。给药结束检测10只/性别/组,恢复期结束检测5只/性别/组。检测指标包括眼科检查、血液学、血清生化、凝血、尿指标、大体解剖和病理组织学检查等。结果试验期间,各组动物眼科检查、笼旁观察及临床观察均未见异常。与同期溶媒对照组相比,动物体重及摄食量未见异常,动物血液学、血清生化指标、凝血指标及尿液指标均未见有毒理学意义的改变,脏器重量、脏器系数及组织病理学检查,未见与给药相关的变化。结论在本试验条件下,SD大鼠连续13周灌胃十味龙胆花胶囊,剂量分别为1、2和4 g/kg·bw,给药结束及恢复期结束时,供试品高剂量组动物各脏器组织均未见明显与供试品相关的组织病理学病变及延迟病理学改变。雌雄动物无可见有害作用水平(no observed adverse effect level,NOAEL)均为4 g/kg,相当于临床用量的59.3倍。Objective To observe the toxicity effects,the development and recovery of toxicity of Shiwei Longdanhua capsule in SD rats after repeated oral gavage for 13 weeks,to determine the dose-effect relationship of toxicity.To predict the adverse reactions that may occur in humans.To determine the toxic target organs and the reversibility of damage and to provide a reference for the dosage design of clinical safety medication and the monitoring of clinical toxicity and adverse reactions.Methods In this experiment,the vehide control group and three dose groups were set.The dosages of the low,medium and high dose group were 1,2 and 4 g/kg·bw,respectively 120 male and female SD rats aged 7-8 weeks were randomly divided into different groups with 15 male and 15 female in each group according to their body weight using Provantis system.The rats were administered via gavage,with a volume of 10 ml/kg,once a day,for 13 consecutive weeks.During the experiment,the animals were observed by cage every day,and clinical observations and body weight and food intake were measured each week.Ten rats/sex/group were tested at the end of the administration,and 5 rats/sex/group were tested at the end of the recovery period.The test indicators included ophthalmological examination,hematology,serum biochemistry,coagulation,urine indexes,gross anatomy and pathological histology.Results No abnormality was found in ophthalmological examination,cage observation and clinical observation.Compared with the vehicle control group during the same period,the weight and food intake of animals in test groups were normal,and no toxicological changes were found in the hematology,serum biochemistry,coagulation and urine indexes of animals.There were no changes related to exposure in organ weight,organ coefficient and histopathological examination.Conclusion Under the conditions of this experiment,SD rats were given with Shiwei Longdanhua capsule for 13 consecutive weeks at doses of 1,2 and 4 g/kg·bw,respectively.At the end of administration and the end of

关 键 词：十味龙胆花胶囊 SD大鼠 重复给药毒性 无可见有害作用水平 

分 类 号：R285.5[医药卫生—中药学] R99[医药卫生—中医学] R114