目的 探讨板蓝根制剂制备过程中主要指标性成分(告依春、尿苷、鸟苷、腺苷、靛玉红)质量分数变化与其药效的相关性,以阐明板蓝根制剂制备过程中的关键影响环节,为后续制备工艺优化提供理论基础。方法 模拟板蓝根制剂制备过程(提取-浓缩-醇沉-干燥-制粒),采用HPLC法测定各阶段化学成分的质量分数变化;以体外羟基自由基清除率为模型,测定各阶段中间体溶液的抗氧化活性;利用聚类分析法、偏最小二乘法和多元线性回归对色谱-药效活性数据进行相关分析。结果 提取-浓缩-醇沉-干燥-制粒等过程中板蓝根制剂化学成分的质量分数与其抗氧化活性整体呈降低的趋势,其中热处理环节(浓缩、干燥)损失较大;分别采用2种计量学方法进行相关分析,结果靛玉红、鸟苷、腺苷质量分数与羟基自由基清除率呈正相关。结论 板蓝根制剂制备过程中的各阶段操作水平对其指标组分的质量分数及药效影响显著,其中浓缩干燥环节为影响其制剂质量的关键环节;靛玉红、鸟苷、腺苷可能是其发挥抗氧化活性的关键药效物质基础。

Objective To investigate the key factors in the process of Isatidis Radix (IR)preparation. The content changes of its main chemical ingredients (epigoitrin, uridine, guanosine, adenosine, and indirubin) and the correlation with its pharmacological activity had been studied, which would providetheoretical foundation for further optimization of process. Methods The process of IR preparation (extracting-concentrating-alcohol sinking-drying-granulation) was simulated. HPLC was employed to determine the contents of the chemical ingredients in each step of IR preparation, and the clearance rate of OH·was used as the model to investigate the antioxidant activity. Cluster analysis, partial least sqμares (PLS), and multiple linear regression (MLR) were used to analyze the correlation between its chromatogram and pharmacological activity. Results The content changes of chemical ingredients from IR preparation were generally decreased on the whole, and the highest loss rate of chemical ingredients occurred in the concentrating-drying process; Two metrological methods had been used to analyze the correlation and the chromatogram of indirubin, guanosine, and adenosine, which was positively related with the clearance rate of OH·.Conclusion Each step in the process of IR preparation had the significant effect on the content of its chemical ingredients and pharmacological activity. The concentrating and drying process may be the key process which would finally influence the quality of preparation. Indirubin, guanosine, and adenosine may be the effective substances of IR with antioxidant activity.

国家自然科学基金资助项目(81560649);江西中医药大学重点学科资助项目(2013jzzdxk048);江西省教育厅科技项目(GJJ14623)