民族药广枣有效部位药代动力学研究

【作者】 王平；

【导师】 孟宪丽； 张艺；

【作者基本信息】 成都中医药大学 ， 药理学， 2004， 硕士

【摘要】 本课题是四川省重大科技攻关项目“中药复方有效部位群确定研究”的重要组成部分。广枣为漆树科植物南酸枣(Choerospondias axillaries(Rox.)Burtt et Hill.)的成熟果实，为藏医和蒙医习用药材之一，临床主要用于气滞血瘀引起的胸痹作痛的治疗。现代药理学研究表明广枣有明显的抗心肌缺血的作用。 为指导临床合理用药和初步揭示抗心肌缺血的药效物质基础，本文采用现代分析方法进行了广枣有效部位的药代动力学研究。 采用结扎左冠状动脉致大鼠心肌缺血模型，筛选出广枣抗心肌缺血的活性部位。对活性部位纯化后得到的广枣有效部位(CEE)进行了药效学验证和化学成分分析，发现其中主要成分为酚酸类。首次以恒流反相离子对色谱法同时测定了CEE中没食子酸(GC)和原儿茶酸(PC)的含量。 首次进行了民族药广枣有效部位的多组分药代动力学研究。发现家兔口服CEE后血清中出现了多个特异性化学成分。采用给药后血清中出现的三个特异性成分(GC、PC和一特异性色谱峰所代表的物质)为指标，进行了CEE的药代动力学研究，结果表明CEE灌胃后，其中的GC和PC在健康家兔体内药代动力学行为分别符合二室开放模型和一室开放模型，特异性色谱峰所代表物质药代动力学行为符合二室开放模型。以上三者的药代动力学参数有极高的相似性，可综合反映CEE快吸收，快分布，中速消除和平均滞留时间(MRT)较短的药代动力学特点，提示临床用药应注意给药时间间隔和提高生物利用度。同时各成分分布比例的差异性反映出民族药作用的多成分多靶点机制。 综上所述，民族药广枣药代动力学研究可以指导民族药的合理用药，可初步揭示民族药药效物质基础和作用机理。更多还原

【Abstract】 The project is an important sect of SiChuan province key technology and development program-"confirmation of effective part of Chinese decoration". Fructus choerospondiatis is the mature fruit of Choerospondias axillaries (Rox.) Burtt et Hill., and has been widely used for curing the Qi stagnation and Blood stasis on clinic by Mongolia medicine and Tibet medicine. It is found that the extract of Fructus choerospondiatis has the significant effluence on antimyocardial ischemic.It has been carried out the studies on pharmacokinetics of CEE for supervising the suitable usage and pilot studying material substance of its antimyocardial ischemic.It is confirmed CEE has the explicit effect of antimyocardial ischemic, then many compounds in CEE are attested to phenolic acids. And it has been firstly resolved by ion-pair RP-HPLC that how to simultaneous determining Gallic Acid (GC) and Protocatechuic Acid (PC) with isocratic elution.Analyzing the compounds in blood after rabbits were orally administered CEE, it was found there are eight distinctive compounds in serum, and it indicated GC and PC in CEE are absorbed. Pharmacokinetics was studied with the methods of quantitive determined the GC, PC and one substance representing by the chromatography peak. It indicated that the pharmacokinetics behavior of these three substances accorded with two opened compartment, one opened compartment and two opened compartment, respectively. Because the parameters of these ones are similar, the results can represent the. kinetics of CEE rapidly absorption, rapidly distribution, middle speed eliminate and short MRT. It also indicated that the influence of ethnomedicine has the peculiarity of more constituents and more targets.更多还原