清肝化瘀颗粒的急性毒性试验研究
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摘要
目的:经口给予小鼠清肝化瘀颗粒进行急性毒性实验,为清肝化瘀颗粒进一步临床应用的安全性提供实验数据。方法:实验用ICR小鼠80只,体重18～21g,随机分为对照组和清肝化瘀颗粒26.8、35.8、48.3、64.4、85.9、116.3、153.8g生药/kg 7个剂量组,每组各10只。禁食15h后灌胃给药1次,给药体积40ml/kg体重,对照组给予同体积水。给药后观察毒性反应,记录不良反应。14d观察期结束时对存活动物剖检,观察各脏器改变。结果:清肝化瘀颗粒一次性经口给予小鼠后,64.4g生药/kg剂量组有2只、85.9、116.3、153.8g生药/kg剂量组10只均急性死亡。Bliss法计算半数致死量(LD50)为69.94g生药/kg(相当于临床剂量的104倍),最大无致死剂量为48.3g生药/kg,最大无毒反应剂量为26.8g生药/kg。除急性死亡外,不良反应主要为腹泻、静卧、步态不稳、翻正反射消失伴肢体僵直。用药14d后存活小鼠各脏器肉眼观察均未见病变。结论:清肝化瘀颗粒给予小鼠26.8g生药/kg(相当于临床剂量的40倍)时无毒性反应;药量达到临床剂量的104倍,即69.94g生药/kg时,达到小鼠半数致死量。提示清肝化瘀颗粒临床拟用剂量(0.67g生药/kg)安全。
Objective:Mice were dosed Qinggan Huayu Particles orally for acute toxicity test, to provide experimental data for further clinical applications safety of Qinggan Huayu Particles.Methods:Eighty experimental ICR mice,weighted 18-21 g,were randomly divided into control group and 7 dosage groups of Qinggan Huayu Particles of 26.8 g,35.8 g,48.3 g,64.4 g,85.9 g,116.3 g,153.8 g crude drug/kg,10 mice in each group.All mice were administered once after fasting for 15 h,the volume of administration was 40 ml/kg body weight,and the control group was given the same volume of water.The toxicity was observed after administration,and adverse reactions were recorded.At the end of the observation period on day 14,the surviving animals were dissected and their organs were observed.Results:There were 2 mice in the 64.4 g crude drug/kg group,and all in the 85.9 g,116.3 g,and 153.8 g crude drug/kg groups died acutely after the medicine was given.The median lethal dose(LD50)as 69.94 g crude drug/kg(equivalent to 104 times the clinical dose),the maximum non-lethal dose is48.3 g crude drug/kg,and the maximum non-toxic reaction dose is 26.8 g crude drug/kg.In addition to acute death,the main adverse reactions were diarrhea,lying still,gait instability,disappearance of righting reflex and limb stiffness.There were no organ change in the surviving mice.Conclusion:There is no toxicity when the dose is 26.8 g of crude drug/kg(equivalent to 40 times of the clinical dose).When the dose is equivalent to104 times of the clinical dose(69.94 g of crude drug/kg),the LD50 of the mice was reached.It is suggested that the clinical dose of Qinggan Huayu Particles(0.67 g crude drug/kg)is safe.
Objective:Mice were dosed Qinggan Huayu Particles orally for acute toxicity test, to provide experimental data for further clinical applications safety of Qinggan Huayu Particles.Methods:Eighty experimental ICR mice,weighted 18-21 g,were randomly divided into control group and 7 dosage groups of Qinggan Huayu Particles of 26.8 g,35.8 g,48.3 g,64.4 g,85.9 g,116.3 g,153.8 g crude drug/kg,10 mice in each group.All mice were administered once after fasting for 15 h,the volume of administration was 40 ml/kg body weight,and the control group was given the same volume of water.The toxicity was observed after administration,and adverse reactions were recorded.At the end of the observation period on day 14,the surviving animals were dissected and their organs were observed.Results:There were 2 mice in the 64.4 g crude drug/kg group,and all in the 85.9 g,116.3 g,and 153.8 g crude drug/kg groups died acutely after the medicine was given.The median lethal dose(LD50)as 69.94 g crude drug/kg(equivalent to 104 times the clinical dose),the maximum non-lethal dose is48.3 g crude drug/kg,and the maximum non-toxic reaction dose is 26.8 g crude drug/kg.In addition to acute death,the main adverse reactions were diarrhea,lying still,gait instability,disappearance of righting reflex and limb stiffness.There were no organ change in the surviving mice.Conclusion:There is no toxicity when the dose is 26.8 g of crude drug/kg(equivalent to 40 times of the clinical dose).When the dose is equivalent to104 times of the clinical dose(69.94 g of crude drug/kg),the LD50 of the mice was reached.It is suggested that the clinical dose of Qinggan Huayu Particles(0.67 g crude drug/kg)is safe.
引文
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[4]中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版)[J].临床肝胆病杂志,2017,33(8):1419-1431.
[5]国家食品药品监督管理局.中药、天然药物急性毒性实验研究技术指导原则[S].2005.
[6]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,2006.108.
[7]Li H,Li X,Bai M,et al.Matrine inhibited proliferation and increased apoptosis in human breast cancer MCF-7 cells via upregulation of Bax and downregulation of Bcl-2[J].Int JClin Exp Pathol,2015,8(11):14793.
[8]李宏捷,谢文利,朱江.黄芩苷的抗肿瘤作用及对肿瘤细胞端粒酶的影响[J].江苏医药,2008,34(4):931-933.
[9]Zhou QM,Wang S,Zhang H,et al.The combination of baicalin and baicalein enhances apoptosis via the ERK/p38MAPK pathway in human breast cancer cels[J].Acta Pharmacol Sin,2009,30(12):1648-1658.
[10]Trabulo S,Cardoso AM,Santos-Ferreira T,et al.Survivin silencing as a promising strategy to enhance thesensitivity of cancer cells to che-motherapeutic agents[J].Mol Pharm,2011,8(4):1120-1131.