基于“效-构-量”导向的疏风解毒胶囊体内过程研究

Shufeng Jiedu capsule, a Chinese patent medicine, has exact curative effect for the treatment of acute upper respiratory infection in clinically. However, its pharmacodynamic material basis is not very clear, and there is no report on the physiological disposition study. Based on previous research of chemical substance basis and anti-inflammatory protection effect, this project intends to screen anti-inflammatory components by UPLC-Q-TOF/MS coupled with NF-κB activity luciferase reporter assay system, and analyze the exposure of pharmaceutical constituents through established plasma fingerprint. By means of the guided analysis in activity, structure and exposure, the key index components with different structural types would be selected, which have anti-inflammatory activity and greater exposure in plasma. With the key index components as PK markers, we can analyze their metabolites and plasma concentrations in rats, and further clarify the metabolic transformation pathway and pharmacokinetic behavior to characterize the qualitative and quantitative physiological disposition of Shufeng Jiedu capsule. The results would provide a theoretical basis for the rational clinical application of Shufeng Jiedu capsule, and provide reference for the study on physiological disposition of other traditional Chinese medicine.

疏风解毒胶囊为治疗急性上呼吸道感染的确有疗效的中成药，但其药效物质基础并不十分清楚，体内过程的研究更未见报道。本项目在前期化学物质基础和抗炎保护作用研究的基础上，拟采用UPLC-Q-TOF/MS整合NF-κB双荧光素酶报告基因系统筛选抗炎活性成分，建立血行成分指纹谱比较各药物成分的体内暴露程度，进行药效活性-结构-暴露量导向的“效-构-量”分析，确定不同结构类型的具有抗炎活性且暴露量较大的关键指标成分；进一步以锁定的关键指标成分作为药代标志物，分析其在大鼠体内的代谢产物及时-量变化，明确代谢转化途径与药代动力学行为，表征疏风解毒胶囊的体内定性-定量过程，将为其临床合理用药提供理论依据，也为其它中药复方的体内过程研究提供方法参考。

疏风解毒胶囊为治疗急性上呼吸道感染的确有疗效的中成药，但其药效物质基础并不十分清楚，体内过程的研究更未见报道。本项目在前期化学物质基础和抗炎保护作用研究的基础上，开展基于“效-构-量”导向的疏风解毒胶囊体内过程研究。采用UPLC-Q-TOF/MS整合NF-κB双荧光素酶报告基因系统，筛选得到10个抗炎活性成分；建立UPLC-Q-TOF/MS血行指纹谱，在大鼠血浆中鉴定得到27个吸收入血的原型药物成分；通过药效活性-结构-暴露量的导向分析，确定大黄素、连翘苷、连翘酯苷A与马鞭草苷为疏风解毒胶囊的关键指标成分，可作为药代标志物。运用质量亏损过滤策略技术筛选鉴定体内代谢产物，分析其代谢转化途径，发现大黄素代谢产物14个，连翘苷代谢产物2个，连翘酯苷A代谢产物5个，马鞭草苷代谢产物3个。药代动力学研究显示，大黄素在15min内即达到较高浓度，体内吸收呈现双峰，可能存在肝肠循环，而马鞭草苷吸收相对较慢，体内半衰期较小，滞留时间较短。综上所述，本项目系统研究了疏风解毒胶囊的体内定性-定量过程，将为其临床合理用药提供理论依据，也为其他中药复方的体内过程研究提供方法参考。