【作者】 洪战英；

【导师】 殷学平； 范国荣；

【作者基本信息】 第二军医大学 ， 药物分析学， 2005， 博士

【摘要】 本文以纯天然止痛验方元胡白芷方中的延胡索乙素消旋体为主要研究对象,以手性固定相-HPLC为主要监测手段,在四氢原小檗碱同类物对映体拆分研究和延胡索乙素对映体体内定量分析方法建立的基础上,首次研究并揭示了延胡索乙素对映体在大鼠生物体液中的立体选择性药代动力学特征;首次研究了延胡索乙素对映体在作用部位脑部不同区域的作用浓度以及经时动态变化,从药代动力学的角度定量地阐明延胡索乙素脑部作用位点药效强度变化的内涵;探讨元胡白芷配伍对延胡索乙素手性特征的影响,提示元胡伍用白芷后具协同增效作用,从药动学的角度证实了方剂配伍的合理性。研究成果可为延胡索乙素及四氢原小檗碱同类物的深入研究以及中药复方配伍规律研究等提供一定的理论基础和技术支持。更多还原

【Abstract】 Tetrahydropalmatine (dl-THP) is a biologically active ingredient in a Chinese herb prescription named Yuanhu-Baizhi. This paper has focused on the enantiomeric separation and chiral pharmacokinetics of THP in animals, using a chiral HPLC method coupled with achiral column. The stereo selective disposition kinetics, such as plasma pharmacokinetics and excretion, of THP enantiomers in rats after an oral dose of the racemate was revealed for the first time. The concentrations of THP enantiomers in plasma, cortex, cerebellum, diencephalon, brain stem, striatum and hippocampus were measured and the striatum displayed significantly higher concentrations. The effects of the ingredients in Yuanhu-Baizhi prescription on the pharmacokinetics of THP enantiomers were also studied. The results of this thesis provided theoretical basis and techniques for further studies on tetrahydroprotoberberines. It was suggested that the pharmacokinetics of Chinese medicines could be used as an effective way of seeking inherent law of complex prescription principle.更多还原