基于有机配位理论和血清药物化学研究青黄散的物效基础

Treatment of leukemia (Leukemia) scattered Qinghuang powder classic recipe, traditional research has focused on the physical effect of the active ingredient and indigo realgar inorganic arsenic. The subject of this current research proposal is according to organic-based medicine with traditional Chinese medicine theory and method of coordination chemistry. We put forward a new hypothesis---'Due to the compatibility of bulk, Qinghuang produce new organic arsenic complexes and enhances its anti-leukemia activity': Firstly, based on the theory of organic coordination chemistry, we try to look for the formation of soluble organic arsenic complexesfrom in vitro chemistry, in vitro biomimetic conditions (artificial gastric juice, artificial intestinal fluid) and in vivo process of ; Secondly, we try to to obtain new soluble organic arsenic complexes and culture single crystalline by column chromatography, LC-MS separation and purification ; Finally, we shall use the single crystals obtained to perform in vivo anti-leukemia activity and to explore possible intrinsic mechanisms. The results can clarify the anti-leukemia effect-based foundation of Qinghuang and further enrich the coordination chemistry of traditional Chinese medicine theory, providing new ideas and methods for substances other basic research of Chinese medicine.

治疗白血病（Leukemia）的经典良方青黄散，传统的物效研究集中于青黛中有效成分和雄黄中的无机砷，本课题基于有机配合理论及血清药物化学方法，提出“青黄散由于配伍产生新的有机砷配合物而增强了其抗白血病活性”的假设，首先根据有机配位化学理论，从体外化学，体外仿生条件（人工胃液、人工肠液）及体内过程寻找形成可溶性有机砷配合物；其次采用柱层析，以LC-MS分离、纯化获得新的可溶性有机砷配合物，并对其进行单晶培养；最后并获得的单晶进行体内外抗白血病活性研究，并探讨可能机制。其结果对于阐明青黄散抗白血病的物效基础奠定基础，同时也丰富了中药配位化学理论，为其它中药复方的物质基础研究提供新的思路和方法。

基于有机配位理论和血清药物化学对青黄散中青黛与雄黄分别进行研究，分别考察了青黄散在大鼠体内雄黄对青黛的影响和青黛对雄黄的影响，研究两者配伍剂量变化与体内活性物质的变化，特别是对有机砷类化合物形成原因展开研究。其次，从体外仿生条件（人工胃液、人工肠液）及体内血清药物化学实验中寻找到可溶性砷类化合物，并对其体内外的抗白血病活性进行研究，确定了“青黄散配伍后在体内形成可溶性有机砷类化合物是其抗白血病作用的药效物质基础”理论，并建立青黄散体内药代动力学评价体系。其结果对于阐明青黄散抗白血病的物效基础奠定理论基础，同时也丰富了中药配位化学理论，为其它中药复方的物质基础研究提供新的思路和方法。