本项目拟基于药效评价的“双态、双属” 体内代谢产物比较研究策略，通过对正在进行Ⅱ期临床的，用于心绞痛治疗的新药丹七通脉片进行正常及病理两种状态下，动物及人体两个种属的药物代谢产物与药效关联性研究。提出丹参酚酸类及三七皂苷类成分在疾病动物模型/患者给药后不同阶段中与正常动物/健康人比对分析后，有明显差异变化的代谢产物群是药效物质基础组成成分的假说。该假说将逐个富集主要代谢产物进行药效学评价来进行验证。在体内代谢产物分析中，采用“从整入微”的研究思路，首先采用质谱成像技术研究代谢产物在动物体内的整体分布情况，然后采用超高效液相-高分辨质谱联用技术对体内微量的代谢产物进行分析、鉴定；在药效评价研究中，采用细胞、组织器官、整体动物的药物评价体系。本项目拟建立整体、全面寻找具有药效活性的中药成分体内代谢产物系统分析方法，并为阐明新药丹七通脉片的药效物质基础及临床给药方案设计提供科学依据。

The project is scheduled, according to an efficacy evaluation-based comparative study strategy for the in vivo metabolites originating from “dual status and dual species”, to perform a study on the relationship between the drug metabolites ( in the rats and human beings respectively under the normal and pathological status) and the efficacy of Dan Qi Tongmai Tablet (DQTT), a new drug indicated for angina currently under Phase II clinical trials. A hypothesis is proposed that the significantly altered metabolite clustering of the phenolic acids of Salvia miltiorrhiza and Notoginseng saponins, by comparison between the normal animals/healthy humans and diseased animal models/patients under different periods of the medication early stage, effect onset, efficacy, composes the therapeutic basis of DQTT. This hypothesis will be validated by the in vitro efficacy evaluation of each enriched metabolite. A “Holistic-to-individual” research idea is employed for the analysis of the in vivo metabolites. Mass spectrometry imaging is primarily used to study the whole-body distribution of the metabolites, and ultra-high performance liquid chromatography- high resolution mass spectrometry is then applied to analyze and identify the minor in vivo metabolites. The well-developed and reliable evaluation system for cardiovascular metabolites that involves cell, organ, and whole animal will be adopted. This project aims to establish a systematic methodology for detecting the efficacy-related in vivo metabolites of the TCM components in an integral and comprehensive manner, and also to provide scientific evidence for clarifying the therapeutic basis and designing the clinical dosage regimen of DQTT.