全三七片单次和重复给药毒性评价研究  

Toxicity Evaluation Study of Single and Repeated Administration for Quansanqi Tablets(全三七片)in Rats

作　　者：谭莹 廖伟 廖文平 李勇 那敏 郭湘楠 杨露 朱兆云 王京昆 TAN Ying;LIAO Wei;LIAO Wenping;LI Yong;NA Min;GUO Xiangnan;YANG Lu;ZHU Zhaoyun;WANG Jingkun(Yunnan Institute of Materia Medica,Kunming 650111,Yunnan,China;Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation,Kunming 650111,Yunnan,China)

机构地区：[1]云南省药物研究所,云南昆明650111 [2]云南省中药和民族药新药创制企业重点实验室,云南昆明650111

出　　处：《辽宁中医药大学学报》2024年第1期15-30,共16页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：云南省重大科技专项(2019ZF016)。

摘　　要：目的 在GLP条件下开展单次给药和重复给药毒性实验,观察全三七片的毒性作用和可逆性,推测毒性靶器官或靶组织,预测临床试验的安全剂量范围,为全三七片的安全性提供试验依据。方法 采用SD大鼠为实验系统,通过观察一般临床体征,称量体质量,评价摄食、饮量,检测血液学、血凝、血清生化学指标和生物标志物,称量脏器重量,计算脏器系数及对主要脏器组织进行病理学检查等方法,评价全三七片24 h内大剂量给药和连续13周持续给药对动物可能产生的毒性及其严重程度。结果 (1)全三七片24 h内2次灌胃的最大给药量为20.0 g·kg^(-1),给药后动物体质量正常增长,观察期内未见动物死亡和出现异常体征。(2)分别以1.5、2.6、6.8 g·kg^(-1)(简称:低、中、高剂量组)重复灌胃给予全三七片13周,可使SD大鼠出现稀便和/或软便及周平均摄食量和饮水量增加,中、高剂量组大鼠体质量增长略缓慢,高剂量组雌鼠血小板膜蛋白-140(GMP140)和雄鼠的红细胞(RBC)、网织红细胞(Retic)计数及百分比、甘油三酯(TG)轻微降低,高剂量组雌鼠肝系数(脏体比)和中、高剂量组雄鼠肝、肾系数(脏体比)增大,上述指标停药后均能恢复正常或呈恢复趋势。结论 (1)全三七片24 h内大剂量给药(相当于临床最大拟用剂量的665倍)具有较高的安全性。(2)全三七片重复给药13周的无不良反应剂量(NOAEL)为1.5 g·kg^(-1)(相当于临床最大拟用剂量的50倍),提示受试物具有较宽的安全剂量范围,但在临床使用过程中应密切关注胃肠系统功能并避免与有类似不良反应的药物合用。Objective Through the single and repeated administration toxicity tests of Quansanqi Tablets(全三七片)under GLP conditions,the characteristics and reversibility of the drug's toxic effects were observed,the toxic target organs or tissues were speculated,and the safe dose and range of clinical trials were predicted.It provides a test basis for the safety of Quansanqi Tablets.Methods SD rats were used to carry out the toxicity test.By observing the general clinical symptoms,weighting and evaluating the food intake and volume of the wate,testing the hematological indicators,hemagglutination indicators,serum biochemical indicators and biomarkers,weighing and calculating the weight and coefficient of organs and conducting pathological examination of major organs and tissues,the possible toxicity and severity of the test substance given in large quantities within 24 hours and continuously for 13 weeks was evaluated.Results(1)The maximum dose of the Quansanqi Tablets administered by gavage twice within 24 hours was 20.0 g·kg^(-1).The weight of the animals increased normally,no animal death and other abnormal signs were found after administration.(2)Repeated administration of Quansanqi Tablets with 1.5,2.6,and 6.8 g·kg^(-1)(low,medium,and high doses for short)for 13 weeks respectively,can make SD rats appear loose stool and/or soft stool,the weekly food intake and drinking water volume increase,the weekly weight growth of middle and high dose rats is slightly slower.The GMP140 of female rats in high dose,the RBC,TG and the Retic count and percentage of male rats in high dose decreased slightly.The liver coefficient(visceral body ratio)of female rats in high dose and the liver coefficient(visceral body ratio),kidney coefficient(visceral body ratio)of male rats in middle and high dose increased,but they all returned to normal or showed a recovery trend after drug withdrawal.Conclusion(1)The high dose of Quansanqi Tablets within 24 hours(equivalent to 671 times of the maximum intended dose for clinical adults)has high

关 键 词：全三七片 SD大鼠片 单次给药毒性 重复给药毒性 

分 类 号：R285.1[医药卫生—中药学]