刘淑兰 周艺林 林鹏 龚卫平 欧阳锐 夏新华

〔摘要〕 目的 优选紫红生肌软膏的醇提工艺参数，为紫红生肌软膏的新药开发提供依据。方法 以栀子苷、连翘酯苷A、羟基红花黄色素A为评价指标，在单因素试验的基础上，以乙醇浓度、加醇量、提取时间为考察因素，采用Box-behnken响应面法设计试验，采用层次分析法-熵权法组合赋权确定各指标权重系数并计算综合评分，从而优化紫红生肌软膏醇提工艺参数。结果 紫红生肌软膏最佳醇提工艺为采用70%的乙醇为溶剂提取两次，第1次加9倍量乙醇提取150 min，第2次加7倍量乙醇提取120 min。该工艺参数综合评分的模型实测值为100.70，与模型预测值接近。结论 优选出的紫红生肌软膏最佳醇提工艺稳定可行，可为紫红生肌软膏进一步开发为新药提供依据。

〔关键词〕 紫红生肌软膏;Box-behnken响应面;醇提工艺;层次分析法;熵权法;栀子苷;连翘酯苷A;羟基红花黄色素A

〔中图分类号〕R283       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2021.04.007

〔Abstract〕 Objective To optimize the alcohol-extraction process parameters of Zihong Shengji Ointment and provide the basis for the new drug development of Zihong Shengji Ointment. Methods The geniposide， forsythiaside A， hydroxysafflor yellow A were used as evaluation indexes. On the basis of single factor experiment， the ethanol concentration， the amount of alcohol added and extraction time were used as investigation factors， the experiments were designed by Box-behnken response surface， and the weight coefficients of each index were determined by analytic hierarchy process-information entropy weight method， and the comprehensive score was calculated， so as to optimize the alcohol-extraction process parameters of Zihong Shengji Ointment. Results The optimum alcohol-extraction process of Zihong Shengji Ointment was 70% ethanol for two times， the first time was added with 9 times ethanol for 150 min， and the second time was added with 7 times ethanol for 120 min. The measured value of the comprehensive score of the process parameters was 100.70， which was close to the predicted value. Conclusion The optimized alcohol-extraction process of Zihong Shengji Ointment is stable and feasible， which can provide basis for the further development of Zihong Shengji Ointment as new drugs.

〔Keywords〕 Zihong Shengji Ointment; Box-behnken response surface; ethanol-extraction process; analytic hierarchy process; information entropy; geniposide; forsythiaside A; hydroxysafflor yellow A

糖尿病是一種慢性疾病，在世界范围内发病率呈逐年增长趋势。糖尿病足是由于糖尿病异常代谢引起下肢神经功能障碍、外周血管结构异常，进而导致足部变形、溃疡形成和肢端坏疽[1-3]。紫红生肌软膏是多年临床实践的经验方，由栀子、连翘、红花等6味中药组成，具有抗炎活血、化腐生肌的功效，临床用于治疗湿热下注型糖尿病足溃疡具有确切疗效[3]。栀子为方中君药，具有清热利湿作用，其活性成分栀子苷具有抗凋亡、抗炎和抗动脉粥样硬化作……