【作者】 董新荣；

【导师】 葛铭；

【作者基本信息】 东北农业大学 ， 临床兽医学， 2008， 硕士

【摘要】 随着集约化养殖的不断发展,母畜产后病发生率一直居高不下,成为严重危害养殖业发展的疾病。为满足实际需要,复方益母草注射液被研制出来。中药注射液由于质量标准不完善、药物代谢研究少以及临床不良反应多,在应用中一直受到很多方面的限制,因此,为确保该制剂的安全性及有效性,本研究对复方益母草注射液进行了药物动力学和安全性研究,旨在为进一步进行临床研究提供科学的理论参考,并为申报兽药新制剂提供依据。根据新药临床前的有关规定,本实验采用高效液相色谱法研究了复方益母草注射液中的三种主要成分盐酸水苏碱、连翘苷和盐酸川芎嗪在大鼠体内的血浆药物代谢动力学,并通过急性毒性实验、安全限量实验、亚慢性毒性实验、热原检查、过敏实验、刺激性实验,评价了该制剂的安全性,实验结果表明:1.大鼠肌肉注射复方益母草注射液后,盐酸水苏碱在血浆中的药—时数据符合一级吸收二室开放式模型,其主要药物动力学参数为:t1/2ka=0.15017h,t1/2α=0.20701h,t1/2β=3.14613h,k12=1.24602h-1,k21=0.37966h-1,kel=1.94218h-1。连翘苷和盐酸川芎嗪的血浆药—时数据也符合一级吸收二室开放式模型,其主要药物动力学参数分别为:t1/2ka=0.15179h,t1/2α=0.20171h,t1/2β=3.11458h,k12=1.22349h-1,k21=0.37030h-1,kel=2.06435h-1;t1/2ka=0.14896h,t1/2α=0.20659h,t1/2β=7.33190h,k12=1.64715h-1,k21=0.19764h-1,kel=1.60427h-1,表明复方益母草注射液经肌肉注射后在大鼠体内吸收迅速,并快速分布到各个组织,在血浆中存在和发挥药效的时间较长。2.大鼠急性毒性实验中口服复方益母草注射液的LD50>76.082g/kg体重,肌肉注射的LD50>19.175g/kg体重,小鼠耐受量大于靶动物用量的300倍以上,亚慢性毒性实验中未出现中毒反应,热原检查、过敏性实验和刺激性实验均符合注射液标准,表明复方益母草注射液安全可靠。更多还原

【Abstract】 With the development of concentrated cultivation, incidence rate of postpartum disease had been increased and it became severe diseases which harmed the development of cultivation industry. Natural Chinese medicine was confined to utilize because of its quality standard, medicine metabolism research and more clinic side-effects. The studies on pharmacokinetics and safety of compound yimucao injecta were to ensure its safety and effectivity. The study would provide scientific theory for clinics study and basis for new animal medicine preparation.According to new medicine regulation, pharmacokinetics of compound yimucao injecta main components- stachydrine, forsythin and ligustrazine in rats’plasma was studied by High Performance Liquid Chromatography and the safety was evaluated via acute toxicity experiment, safty dose experiment, subchronic toxicity experiment, pyrogen experiment, allegic experiment and stimulation experiment. The results showed:1. Injected rats with compound yimucao injecta, the concentration–time course of stachydrine in rats’plasma could be described by a two-compartment open model with first order absorption, the main pharmacokinetic parameters were as follows: t1/2ka=0.15017h, t1/2α=0.20701h, t1/2β=3.14613h, k12=1.24602h-1, k21=0.37966h-1, kel=1.94218h-1. The concentration–time course of forsythin and ligustrazine in rats’plasma could be also described by a two-compartment open model with first order absorption, the main pharmacokinetic parameters were as follows: t1/2ka=0.15179h, t1/2α=0.20171h, t1/2β=3.11458h, k12=1.22349h-1, k21=0.37030h-1, kel=2.06435h-1; t1/2ka=0.14896h, t1/2α=0.20659h, t1/2β=7.33190h, k12=1.64715h-1, k21=0.19764h-1, kel=1.60427h-1. These showed that compound yimucao injecta was absorbed quickly, spread to each organ and eliminated slowly.2. Compound yimucao injecta oral LD50 was more than 76.082g/kg BW and injected LD50 was more than 19.175g/kg BW in rats’acute toxicity experiment; mice’s tolerance dose was as more three hundred times than practical animal’s dose; There was no toxic reaction in subchronic toxicity experiment. The results of pyrogen test, supersensitivity and stimulus experiment accorded with injecta standard. These showed compound yimucao injecta was safe.and reliable.更多还原