中文摘要
异常子宫出血是妇科常见病症,宫血宁胶囊(主要成分重楼)在其临床治疗上有着独特的作用。随着重楼资源危机,宫血宁胶囊临床应用受限。丫蕊花作为可替代资源,具有明显的缩宫止血活性。基于前期研究和文献判断:丫蕊花中主要药效物质基础可能包括两部分,一是有止血活性的螺甾烷成分Tg、Pb、CHY,另一是高含量无活性但在体内可以转化为Tg的呋甾烷苷Th。课题拟进行以下研究:①丫蕊花各活性成分在体内的吸收、代谢、分布规律研究,揭示各活性成分的药代动力学特征;②在体内外确证Th可转化为Tg以及转化的条件、程度和速度等重要参数;③明确主要活性成分代谢过程中对P450代谢酶的影响;④建立子宫异常出血模型,进一步阐明活性成分体内血药浓度、药效与时间的三维关系。通过运用“吸收-代谢-转化”和药效关系的研究模式,对丫蕊花活性成分的代谢规律进行多途径、多角度验证。同时也为呋甾烷型皂苷类药物的代谢转化研究提供新思路。
英文摘要
Abnormal uterine bleeding (AUB) is the most common symptom in gynecopathy.Gong-xue-ning capsule, the preparation of Paris polyphylla, is widely usd for the treatment of ABU. However, Paris Polyphylla is facing with plant resource crisis, the application of Gong-xue-ning is limited in clinic.Ypsilandra thibetica has potent uterine contraction hemostasis, and will replace Paris polyphylla sanguinely.Based on our previous studies and literature, we make concludes that there are two active hemostatic components in Ypsilandra thibetica: one is effective hemostatic Spirostane glycoside components (Tg, Pb, CHY).The other is inactive furostanol glycoside Th that is riched in Ypsilandra thibetica, which can transform into Pb in vitro and vivo. On account of our early works, we put forward four research objectives. First of all, we plan to use LC/MS-MS to confirm absorbtion, metabolism, distribution and pharmacokinetic parameters of Tg, Pb, CHY. Secondly, we are going to explore the condition, level and rate of furostanol glycosides Th invert intoTg by using vivo and vitro experiments.Thirdly, we expound how the active hemostatic components affect on CYP450. At last, we will develop AUB model to clarify the relationship of plasma concentration, efficacy and administration time. We set up “Absorption-Metabolism-Transformation” model and combine with drug potency to probe metabolic processes of Ypsilandra thibetica in different angles. Meanwhile, we also give an example for other furostanol glycosides study.
