2020年3月,我国原创降血糖天然药物"桑枝总生物碱片"获批上市,成为10几年来我国首个获批的中药创新药,也是糖尿病治疗领域唯一有效组分天然药物.在桑枝总生物碱的研发秉承中药传统理论并结合现代药理学研究方法,以确定桑枝中具有降血糖作用的有效组分及评价其药效特点及药理作用机制,故桑枝总生物碱具有其他中药不可比拟的作用靶点清晰、物质基础明确和降血糖作用显著等特点,其广泛的糖尿病治疗综合获益优于单纯糖苷酶抑制剂,具有天然药物独特的多重药理作用优势.本文从药理学研究角度,回顾利用现代药理学研究手段从"中药宝库"中寻找降糖药物过程,以及采用现代药理学手段及理念完善药效学评价体系,并广泛挖掘桑枝总生物碱多重药理作用特点及潜在机制.评述利用现代药理学研究理念,从天然药物中获取有效活性成分和新药研究中需要突破的技术瓶颈和理念创新,旨在为创新中药发展的"传承精华、守正创新"提供参考.

基于疗效与安全性的临床价值是评价药品的最终标准.只有做到物质基础明确、质量准确可控、产品稳定均一,才能确保临床疗效.药学研究的高技术壁垒和规模化发展的制约,是限制有效组分天然药物发展的关键环节.近期降血糖原创天然药物"桑枝总生物碱片"获批上市,成为10几年来我国首个获批的中药创新药,也是糖尿病治疗领域唯一有效组分天然药物.本文从有效组分的科学筛选、微量水溶性生物碱的提取分离与纯化、物质基础及其结构鉴定、复杂体系的质量控制、规模化放大的技术集成制约等环节,评述药学研究和规模化发展的应对策略及取得的突破,旨在为中医药发展理念"传承精华、守正创新"提供参考.

Objective] To select optimum regenerating agent of ion-exchange resin and optimize purification of mulberry alkaloids based on the pKa of the alkaloids and the pI of amino acids. [Methods] The 732 resins were regenerated with hydrochloric acid and different pH buffer solution, respectively. The productions were determined by RP-HPLC with pre-column derivatization. This article calculated the leakage amount of alkaloids and amino acids the adsorbing amount. Meanwhile it also determined the peak ratio of alkaloids in products. [Results] Ultimately, the total amino acids leaked in a short time with the buffer solution at pH 4.6 as regenerating agent. However, both of the alkaloids and amino acids didn’t leak with hydrochloric acid as regenerating agent. The adsorption amount was increased from 1.84 to 2.23 mg/g with the buffer solution at pH 4.6 compared to pH 5.6. The relative peak ratio of the alkaloids in productions is 79.6%with the buffer solution at pH 5.6 as regenerating agent, and 23.6%with hydrochloric acid as regenerating agent. [Conclusion] Through adjusting the pH of resin separation and controlling the dissociation degree of the alkaloids and the amino acids, the purity of the production was improved with decreased adsorption of amino acids and increased selectivity of the resin.