基于"汤液相态-组分吸收-毒性表达"研究附子畏甘草配伍减毒机制

Decoction is the basic pattern of traditional Chinese medicine(TCM). Some research indicated that there are some direct correlations between physico-chemical property and pharmacological effects of decoction, however at present there are few studies focus on correlations between changes of phases of decoction and attenuated effects during compatibility process. Our early research shows that decoction of co-boiling Radix Aconiti Lateralis and Radix Glycyrrhizae, can affect the content and form of toxicity constituent, meanwhile it can change the physico-chemical property of decoction in vitro and component absorption and expression in vivo. So we have a new idea that mutual restraint between Radix Aconiti Lateralis and Radix Glycyrrhizae is based on the process of co-boiling, “diversity” of component chemical form in “mixture” decoction can lead to “derangement” intestinal absorption and then cause nonequilibrium effective expression of toxicity component，achieving the purpose of reducing toxicity.. The research is based on “mutual restraint” compatibility thoughts. According to the TCM complex system and multiple-level expression and the basic principles of chemical thermodynamics, based on different forms of toxicity component in vitro and absorption in vivo during the compatibility process , and use advanced technologies to recognize chemical form of component→ to express macroscopic physico-chemical property of phase of decoction→ to analyze gastrointestinal absorption dynamics, using Information Fusion methods to investigate the law in which the co-boiling decoction play a big role in treating diseases: “different phases of decoction→ the form of chemical forms→gastrointestinal absorption→effective expression”. In order to reveal the key point of link of Radix Aconiti Lateralis and Radix Glycyrrhizae, to provide a new methods of studying theory of TCM seven methods in prescription compatibility.

中医临床用药基本形式为汤液，已有研究表明中药汤液理化性质与其药效有直接相关性，但目前较少关注中药配伍前后汤液相态改变与配伍药效作用相关性。前期研究揭示，附子-甘草合煎影响汤液中毒性组分含量和形态，同时改变体外汤液理化性质和体内组分吸收和表达。为此，提出假说：附子畏甘草是基于合煎过程，“混相”汤液中组分化学形态的“多样性”导致成分胃肠吸收的“不同步”，从而造成毒性组分的非均衡效应表达，达到减毒目的。. 基于中医“附子得甘草而后缓”的配伍理论，依据中药体系复杂性和机体表达多层次性，借助化学热力学基本原理，立足于配伍前后毒性组分的体外形态和体内吸收角度，通过识别成分化学形态→表征汤液“相态”宏观理化性质→解析毒性组分的胃肠吸收动力学，利用信息融合手段，探讨“汤液相态—化学形态—胃肠吸收—效应表达”传变规律，以揭示附子甘草配伍减毒的关键作用环节，为中药七情配伍理论研究提供新思路。

“附子-甘草”药对为中医临床回阳救逆要方，其配伍具有增效和减毒两方面效应。而汤液是中医用药基本形式，已有研究表明中药汤液理化性质与其药效有直接相关性。课题立足于汤液本体的复杂性和中药作用的多层次性，通过研究“汤液相态–化学形态–胃肠吸收–效应表达”的相关性和传递性，表征汤液微粒状态与混相体系相关性，以及解析成分吸收与表达的相关性，将中药物质基础的体外形态与体内表达相关联，有利于探索“相态表征”与“效应表达”相关联的中药七情“相畏/相杀”配伍研究新思路，是进一步完善组分中药思想的科学性研究模式的需要。以汤液本体物理相态整体表征有效组分的宏观表达，有利于从“组分整体-宏观表达”角度诠释附子与甘草“配伍减毒”作用机制，揭示了“附子-甘草‘相畏/相杀’配伍减毒是基于配伍合煎后，“混相”汤液中成分化学形态的“非均一”性导致成分胃肠道吸收的“不同步”，而造成毒性成分的非均衡效应表达的重要科学内涵。本项目开展过程中，因负责人的失误，有3篇公开发表的论文未标注资助编号，现已录用3篇，待发表论文2篇；申请专利2项；研究结果参加全国性、国际学术交流会议3次。