紫杉胶囊急性毒性和反复给药毒性实验研究  

Experimental study on acute and repeated dose toxicity of Zishan caplule

作　　者：靳洪涛[1] 李慧[1] 李晋[1] 丁晓霜[1] 刘岩[1] 李成合[1] 黄明芳[1] 王爱平[1] 

机构地区：[1]中国医学科学院药物研究所安评中心,北京100050

出　　处：《中国现代医药杂志》2009年第5期12-14,共3页Modern Medicine Journal of China

摘　　要：目的观察紫杉胶囊的急性毒性和反复给药毒性,指导临床安全合理用药。方法急性毒性采用最大给药剂量法(10g/kg),观察给药后小鼠出现毒性反应。反复给药毒性实验分为0.25、0.5、1.0g/kg3个给药组(分别相当于临床人用量的8、17、33倍)及溶剂对照组,连续给药90天。停药后恢复期观察4周。检测指标包括动物一般状况、血液学和凝血、血清生化、尿检查及病理组织学等内容。结果急性毒性实验给药后部分动物观察到了眼睑下垂,活动减少,第2天、第4天各有1只小鼠死亡。紫杉胶囊0.5、1.0g/kg连续给药90天。可见雌性大鼠进食量一过性降低,体重下降;AST和ALT增高,给药结束时组织病理学检查可见0.5、1.0g/kg组肝脏片状坏死;骨髓血涂片结果显示骨髓造血细胞轻度抑制,恢复期结束时均未见异常。结论ICR小鼠单次灌胃紫杉胶囊的LD50大于10g/kg。SD大鼠灌胃紫杉胶囊90天反复给药毒性试验,其无毒反应剂量为0.25g/kg。0.5、1.0g/kg动物毒性反应主要为可逆性的肝脏毒性和骨髓轻微抑制作用。上述研究结果为紫杉胶囊的临床安全合理应用提供了参考。Objective To observe the acute and repeated dose toxicity of Zishan caplule. Methods The acute toxicity study was conducted with the maximum tolerance dose method by oral dose of 10g/kg. For the repeated dose toxicity study, Zishan capsule suspended in 0.5% methylcellulose vehicle was administered via oral gavage, once daily, at doses of 0.25,0.5,1.0 g/kg for 3 consecutive months. Parameters evaluated included daily clinical signs, periodic hematology, clinical chemistry,and urinalysis determinations and histopathology examination. Results In acute toxicity study, blepharoptosis,reduced activity was observed after dosing and one mouse died at the 2nd day and one died at the 4th day. In repeated dose toxicity study, decreased food consumption and body weight, increased AST and ALT and liver necrosis,mild suppression of bone marrow hematopoietic cells were observed at the dose of 0.5 and 1.0g/kg. There were no toxicologically relevant finding at the end of recovery period. Conclusion The LD50 of Zishan capsule is 〉10g/kg and the no observed adverse effect level is 0.25g/kg. Drug-related toxicity are limited to liver toxicity and mild suppression of bone marrow at the 0.5,1.0g/kg dose level. These data may provide useful information for clinical use.

关 键 词：紫杉胶囊 急性毒性 反复给药毒性 肝脏毒性 骨髓抑制 

分 类 号：R96[医药卫生—药理学]