肠胃宁胶囊安全性评价研究
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摘要
目的研究肠胃宁胶囊单次和重复给药的临床前安全性,为临床用药提供参考。方法 40只小鼠分为肠胃宁胶囊组和空白对照组,每组20只小鼠,肠胃宁胶囊给药剂量为32 g/kg,空白对照组给予同体积纯水,详细观察动物体征至药后14 d,剖检肉眼大体观察各脏器形态。120只大鼠分为肠胃宁胶囊9、3、1 g/kg剂量组和空白对照组,每组30只大鼠,连续灌胃给药13周,分别于给药13周和停药后4周时取部分大鼠进行血液学指标、血液生化学指标、病理组织学检查。结果肠胃宁胶囊以32 g/kg剂量单日灌胃给药,药后观察至第14天小鼠未见明显毒性反应。肠胃宁胶囊9、3、1 g/kg剂量连续灌胃给药13周,大鼠体重、血液学、血液生化学指标及组织病理学未见明显毒性反应。结论肠胃宁胶囊小鼠单次给药最大给药量为32 g/kg;大鼠重复给药13周最大无毒反应剂量大于9 g/kg。
Objective To study the safety of the Chang Wei Ning Capsule and to provide a reference for clinical application.Methods Forty mice(males and females) were randomly divided into a Chang Wei Ning Capsule group and a normal control group,each containing twenty mice.Mice of the test group received 32 g/kg body weight Chang Wei Ning Capsule,while those of the control group received the same volume of pure water.A detailed observation of the mice,including examination of viscera morphology by naked eye,was conducted until day 14 post-drug administration.One hundred and twenty rats(males and females) were randomly divided into a normal control group and three different Chang Wei Ning Capsule dosage groups(9,3,1 g/kg bodyweight).The rats received consecutive intragastric administrations of Chang Wei Ning Capsule over a 13-week period.In addition to observing the general condition of the animals,body weight,blood,hepatic function and renal function measurements,and a histopathology analysis,were performed after the13 week treatment duration and at four weeks-post drug withdrawal.Results No toxic reaction was observed in mice that received intragastric administrations of Chang Wei Ning Capsule(32 g/kg).No abnormal reaction was also observed in the rats of all dosage groups that received intragastric Chang Wei Ning Capsule over a 13-week period.Conclusions The maximum administered dose of Chang Wei Ning capsule in mice was 32 g/kg body weight in a single-dose toxicity test.No observed adverse effects were observed in rats receiving up to 9 g/kg drug per day in repeated-dose toxicity tests.
Objective To study the safety of the Chang Wei Ning Capsule and to provide a reference for clinical application.Methods Forty mice(males and females) were randomly divided into a Chang Wei Ning Capsule group and a normal control group,each containing twenty mice.Mice of the test group received 32 g/kg body weight Chang Wei Ning Capsule,while those of the control group received the same volume of pure water.A detailed observation of the mice,including examination of viscera morphology by naked eye,was conducted until day 14 post-drug administration.One hundred and twenty rats(males and females) were randomly divided into a normal control group and three different Chang Wei Ning Capsule dosage groups(9,3,1 g/kg bodyweight).The rats received consecutive intragastric administrations of Chang Wei Ning Capsule over a 13-week period.In addition to observing the general condition of the animals,body weight,blood,hepatic function and renal function measurements,and a histopathology analysis,were performed after the13 week treatment duration and at four weeks-post drug withdrawal.Results No toxic reaction was observed in mice that received intragastric administrations of Chang Wei Ning Capsule(32 g/kg).No abnormal reaction was also observed in the rats of all dosage groups that received intragastric Chang Wei Ning Capsule over a 13-week period.Conclusions The maximum administered dose of Chang Wei Ning capsule in mice was 32 g/kg body weight in a single-dose toxicity test.No observed adverse effects were observed in rats receiving up to 9 g/kg drug per day in repeated-dose toxicity tests.
引文
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[3]曹明成,黄泰康.我国有毒中药的研究进展综述[J].中国药业,2016,25(2):9-13.
[4]药物非临床安全性研究技术指导原则[S].国家食品药品监督管理局药品审评中心,2014:21-33.
[5]张颖,马玉奎,戴晓莉,等.多柔比星脂质体注射液与多柔比星注射液大鼠重复给药毒性的比较[J].中国比较医学杂志,2016,26(6):23-27.
[6]李波,袁伯俊,廖明阳.药物毒理学[M].北京:人民卫生出版社.2015:523-525.
[7]戴晓莉,戴学栋,郭峰,等.注射用右旋雷贝拉唑钠大鼠13周重复给药毒性研究[J].中国药物警戒,2016,13(7):389-393.