雷公藤配伍甘草减毒增效研究

【作者】 马哲；

【导师】 梁茂新；

【作者基本信息】 辽宁中医药大学 ， 方剂学， 2011， 博士

【摘要】 目的:基于中药配伍理论,以有毒中药雷公藤为示范揭示传统中药配伍减毒增效理论的科学内涵,初步揭示有毒中药雷公藤与解毒中药甘草配伍减毒增效的药效物质基础与作用机制。材料与方法:1.采用高效液相色谱法对雷公藤、甘草的提取工艺进行研究,建立了两药物的含量测定方法。2.对雷公藤、甘草配伍前后成分的变化进行研究,初步探索两药物配伍减毒增效的物质基础。3.对雷公藤甲素与甘草酸配伍前后进行药动学研究,对比配伍前后药动学参数的变化,对雷公藤甲素配伍减毒增效的机制进行研究。4.对雷公藤与甘草配伍进行毒理学和药效学研究,对甘草配伍雷公藤的减毒增效作用进行评价。结果:1.对雷公藤和甘草进行了提取工艺研究,经高效液相色谱检测证明该工艺稳定、可靠,为进一步对两药物进行研究提供了实验基础;2.雷公藤与甘草配伍后,雷公藤甲素的含量有所降低,该作用可能与甘草酸铵的络合作用有关;3.对两药物进行药代动力学研究时发现,与甘草酸铵配伍后雷公藤甲素的最大血药浓度降低,且半衰期延长;4.雷公藤与甘草配伍的毒理学和药效学实验表明,甘草对雷公藤具有良好的减毒增效作用。结论:1通过高效液相色谱法,对中药雷公藤与甘草配伍前后抗风湿有效成分雷公藤甲素进行了含量测定研究,结果发现甘草酸能使雷公藤甲素含量降低,从而为中药雷公藤与甘草配伍降低毒性提供了佐证。2对中药雷公藤和甘草配伍前后药代动力学进行了研究,结果发现,雷公藤甲素的半衰期(T_1/2)延长、最大血药浓度(C_max)减小。说明雷公藤在甘草的影响下,是抗风湿作用温和毒性下降、作用时间延长。3经实验动物抗炎、镇痛等药效实验证明,雷公藤配伍甘草后,抗风湿作用增强,从而为中药增效理论提供了现代科学依据。通过小鼠急性毒性实验证明,中药雷公藤配伍甘草后,半数致死量(LD₅₀)有所提高,虽然组间差异不显著,但为甘草雷公藤配伍后减毒作用提供了实验依据。4.经课题研究发现,中药配伍减毒增效的机制可能与解毒药物改变了毒性药物入血后的存在方式和代谢过程有关。更多还原

【Abstract】 Purpose:Based on Chinese compatibity theory, the model, represented by toxic Chinese medicine Tripterygium, reveals the scientific content of traditional Chinese medicine theory on toxicity reducing and efficacy enhancing, and initially reveals the effective material basis of toxicity reducing and efficacy enhancing about toxic medicine Tripterygium compatible with detoxifying herbs Licorice.Material and method:1. Establish a method for the determination of Tripterygium and Licorice, under the research of the extraction of the two medicine via high performance liquid chromatography.2. Initially explorer the the material basis of toxicity reducing and efficacy enhancing of Tripterygium compatible with Licorice, by determining content of the composition in the medicines.3. Comparing the pharmacokinetic parameters of triptolide compatibility with glycyrrhizic acid, investigate the mechanism of toxicity reducing and efficacy enhancing. 4. Evaluate the effect of toxicity reducing and efficacy enhancing on Tripterygium compatible with Licorice by studies on toxicological and pharmacodynamic of the two medicines.Results:1. The extraction process of tripterygium and licorice studied by high performance liquid chromatography proved that the process is stable, reliable, in order to further study the two drugs provide an experimental basis.2. After tripterygium compatible with Licorice, the content of triptolide decreased, the effect may relate with the complexation of ammonium and licorice;3. On the pharmacokinetics of two drugs, the study found that with compatibile of licorice ammonium triptolide reduced the maximum plasma concentration and prolonged half-life;4. The toxicology and pharmacodynamic results of tripterygium and Licorice show that licorice has good effect of toxicity reducing and efficacy enhancing. Conclusion:1. Investigating the content of triptolide in the Tripterygium, a antirheumatic Chinese medicine, compatible with Licorice, the result showed that glycyrrhizin can reduce the content of triptolide, and supported the theory of toxicity reducing and efficacy enhancing.2. Reseaching the pharmacokinetics of troptolide after compatible with Licorice, the results showed that the half-life (T_1/2) of triptolide extended and the maximum plasma concentration （Cmax） of triptolide decreased. Under the influence of licorice, anti-rheumatic of triptolide is mild and toxicity decreased, effect become longer.3. The studies showed that the anti-rheumatic effect of Tripterygium increases, via anti- inflammatory and analgesic experimental, so it provides a modern scientific basis for the thoery of toxicity reducing and efficacy enhancing. Acute toxicity test in mice proved that traditional Chinese medicine Tripterygium compatibility with licorice, the median lethal dose （LD50） has increased, although the difference between the groups was not significant, but for the compatibility of licorice triptolide attenuated role in providing an experimental basis.4. The research found that traditional Chinese medicine compatibility attenuated synergistic mechanism may be changed with the detoxification of drug toxicity drugs into existence after the blood and metabolic processes.更多还原