基于吸收-代谢模型的金铃子散复方配伍研究

Study on compound compatibility of Jinglingzi powder based on absorption-metabolism model

目的:以经典方金铃子散为范例,建立适合中药复杂系统研究的吸收-代谢模型,探讨金铃子散不同配比方吸收行为、吸收-代谢行为与复方配伍的相关性。方法:针对药物体内过程的特点建立中药吸收-代谢研究的体外模型,将药物的肠吸收模型和肝微粒体代谢模型结合起来体外模拟药物的吸收-代谢过程,HPLC定量分析金铃子散可吸收组分及吸收-代谢组分。结果:该模型可用于中药的吸收和代谢过程研究;金铃子散提取物中15个主要组分中的10个组分可被小肠吸收,经A-M模型代谢后出现一个新的组分峰;金铃子散组分吸收比与配伍相关,川楝子是影响主要组分吸收比(Ar)和吸收-代谢比(Mr)的主要因素,延胡索次之,方1和方9主要组分吸收比最大。结论:建立了适合中药复杂体系研究的吸收-代谢模型并用于金铃子散复方配伍研究;方剂的配伍影响金铃子散可吸收组分比,从体外药代(吸收-代谢差异)的层面阐释方剂配伍理论内涵:所谓的"君药"(川楝子)是影响全方整体吸收、吸收-代谢的主要因素,臣使药(延胡索)是处于从属地位的因素。

Objective： To establish an absorption-metabolic model suitable for studying the complex traditional Chinese medi- cine（TCM） system, with the classic Jinlingzi Powder formula as the example, in order to explore the correlation among absorption be- havior and absorption-metabolism behavior of different Jinlingzi Powder formulas and their compound compatibility. Method ： An ab- sorption-metabolic model suitable for TCM study was established according to in vivo characteristics of drugs, to combine the intestinal absorption model with the liver microsomal metabolism model. A quantitative analysis was conduced for absorbable components of Jin- lingzi Powder and its absorption-metabolism components by HPLC. Result： The model could be used for studies on the absorption-me- tabolism process of TCM. Among the 15 main components which were derived from Jinlingzi Powder extracts, 10 could be absorbed by intestinal tract. A new component peak was shown after metabolism with the A-M model. The absorbable components of Jinlingzi Pow- der were related to its compatibility. Toosendan was found to be the major factor impacting the main component-absorption ratio （At） and absorption-metabolism ratio （ Mr）, followed by Rhizoma Corydalis. Conclusion： The absorption-metabolism model suitable for studying the complex traditional Chinese medicine system was established and used for the study on compound compatibility of Jinglingzi Powder. The compatibility of the formula has an impact on absorbable component ratio of Jinlingzi Powder, which helps interpret the theory of formula compatibility from the angle of in vitro compound pharmacokinetics （ the difference between absorption and metabo- lism）. Toosendan is the main factor impacting overall absorption and absorption-metabolism, while Rhizoma Corydalis is the minor factor.