苏苏小儿止咳颗粒对幼龄大鼠的长期毒性试验研究
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摘要
目的对苏苏小儿止咳颗粒进行幼龄SD大鼠长期毒性试验研究,为其提供临床前安全性评价。方法苏苏小儿止咳颗粒高、中、低剂量(以生药计30、15、5 g/kg)连续ig给药30 d。观察指标包括一般观察、体质量、摄食量、行为学测试、雌二醇、睾酮、胫骨长度、尿液、血液学、凝血指标、血液生化、电解质、脏器质量、脏器系数及组织病理学检查等。结果 30 g/kg剂量组雄鼠给药期间出现体质量增长缓慢,恢复期可恢复正常。其余动物未见明显药物相关毒性反应,停药后未见迟缓毒性发生。结论在本试验条件下,苏苏小儿止咳颗粒对幼龄大鼠的无毒反应剂量为15 g/kg,相当于临床拟用剂量的22倍。
Objective Preclinical safety study was conducted to assess the long-term toxicity effects of Susu Xiao'er Zhike(SSXEZK) Granules in juvenile rats,and provide preclinical safety evaluation for clinic.Methods Daily ig administration of SSXEZK Granules at 30,15,and 5 g/kg for 30 d was used in high,medium,and low dose groups,respectively.The long-term toxicity effects of SSXEZK Granules was determined by general observation of the animals,and monitoring the changes of their body weight,food intake,behavioral test,estradiol,testosterone,tibial length,urine,faeces,hematology,blood coagulation,blood biochemistry,electrolyte,organ weight and organ index.Histopathological examination was conducted after sacrifice.Results All animals had no significant toxicity and no delayed toxicity occurred after treatment with various doses,except that the body weight growth of male rats was retarded treated with 30 g/kg dose.Conclusion In the situation of this experiment,the NOAEL of SSXEZK Granules in rats was 15 g/kg,which was equivalent to 22 times of the suggested dose in clinical use.
Objective Preclinical safety study was conducted to assess the long-term toxicity effects of Susu Xiao'er Zhike(SSXEZK) Granules in juvenile rats,and provide preclinical safety evaluation for clinic.Methods Daily ig administration of SSXEZK Granules at 30,15,and 5 g/kg for 30 d was used in high,medium,and low dose groups,respectively.The long-term toxicity effects of SSXEZK Granules was determined by general observation of the animals,and monitoring the changes of their body weight,food intake,behavioral test,estradiol,testosterone,tibial length,urine,faeces,hematology,blood coagulation,blood biochemistry,electrolyte,organ weight and organ index.Histopathological examination was conducted after sacrifice.Results All animals had no significant toxicity and no delayed toxicity occurred after treatment with various doses,except that the body weight growth of male rats was retarded treated with 30 g/kg dose.Conclusion In the situation of this experiment,the NOAEL of SSXEZK Granules in rats was 15 g/kg,which was equivalent to 22 times of the suggested dose in clinical use.
引文
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[7]US FDA.Guideance for industry nonclincial safety eveluation of pediatric drug products[EB/OL].(2014-12-11)[2018-01-28].www.fda.gov/downloads/drugs/guidancecompliancere gulatoryinformation/guidances/ucm079247.pdf.
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[10]光红梅,王庆利.FDA儿科药品的非临床安全性评价指导原则简介[J].中国新药杂志,2015,24(6):627-631.
[2]井潇,高杰,吴纯启,等.儿童药物安全性评价研究进展[J].国际药学研究杂志,2016,43(4):608-614.
[3]白金山,见国繁,付国兵,等.特定穴推拿配合艾灸治疗小儿风寒咳嗽经验[J].环球中医药,2016,9(7):854-855.
[4]黄芳华,朱飞鹏,笪红远,等.中药儿科用药非临床安全性评价的一般考虑[J].中国新药杂志,2015,24(24):2779-2781.
[5]黄芳华,王庆利,Jim Ridings.对儿科药物开发的非临床安全性评价的考虑[J].中国新药杂志,2016,25(18):2052-2058.
[6]胡晓敏,王庆利,孙涛.儿童用药的非临床安全性评价研究和案例[J].中国临床药理学杂志,2014,30(9):836-837.
[7]US FDA.Guideance for industry nonclincial safety eveluation of pediatric drug products[EB/OL].(2014-12-11)[2018-01-28].www.fda.gov/downloads/drugs/guidancecompliancere gulatoryinformation/guidances/ucm079247.pdf.
[8]孙祖越,周莉,韩玲.儿科用药非临床安全性评价要则及中药评价的特殊性[J].中国药理学与毒理学杂志,2016,30(1):13-20.
[9]孙祖越,周莉.儿科用药非临床安全性评价中方案设计的策略[J].中国新药杂志,2016,25(21):2473-2482.
[10]光红梅,王庆利.FDA儿科药品的非临床安全性评价指导原则简介[J].中国新药杂志,2015,24(6):627-631.