目的 探讨甘草-马钱子配伍汤液沉积相态的释放行为,为甘草-马钱子配伍减毒提供科学参考。方法 建立沉积相态释放测定HPLC法,通过体外释放实验,追踪沉积相态在蒸馏水、人工胃液、人工肠液等不同介质中主成分的释放行为,并对其释放结果进行拟合研究分析。结果 甘草酸、马钱子碱以及士的宁在人工肠液中的释放量较大,且马钱子碱>甘草 酸>士的宁。马钱子碱和甘草酸均与一级动力学模型拟合结果最佳,士的宁与Higuchi模型拟合结果最佳。结论 甘草-马钱子沉积相态主要毒效成分呈现出难溶性骨架材料缓释制剂的释放特性,毒(效)成分士的宁可能以沉积共聚体形式存在,在体释放呈缓释行为而减毒;同时,甘草酸的释放对减毒增效起到协同作用。

Objective To investigate the release behavior of the sedimentary phase of the Gancao (Glycyrrhizae Radix et Rhizoma, GRR)-Maqianzi (Strychni Semen, SS) compatibility decoction, and provide scientific reference for the toxicity reduction of GRR-SS compatibility. Methods HPLC was used for quantitative detection of effective substances and toxic substances, and in vitro model release experiment was used to trace the release characteristics of representative components in different media such as distilled water, artificial gastric juice, artificial intestinal juice, and the release results were fitted and analyzed. Results The release amount of glycyrrhizic acid, strychnine and brucine in artificial intestinal fluid was large, with the sequence of brucine > glycyrrhizic acid > strychnine. Brucine and glycyrrhizic acid were best fitted to the first-order kinetic model, strychnine had the best fitting results with Higuchi model. Conclusion The main toxic and effective components in the sedimentary phase of GRR-SS show the release characteristics of slow-release preparations of poorly soluble matrix materials, and the toxic components exist in the form of sedimentary copolymer, which show sustained-release behavior with reduce toxicity. At the same time, the release of glycyrrhizin plays a synergistic role in reducing toxicity and increasing efficiency.

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国家自然科学基金资助项目（82173997）；国家自然科学基金资助项目（81703724）；黑龙江省博士后科研启动金项目；黑龙江省“头雁”团队；黑龙江中医药大学健康产业专项课题（jkcy04）