摘要
目的运用质量源于设计理念(QbD),优化小儿腹痛草标准汤剂的制备工艺,并建立其质量标准。方法根据中药质量标志物理论预测分析关键质量属性;采用失效模型与影响分析筛选关键工艺参数(CPPs);建立关键质量属性的测定方法;根据单因素实验确定初步范围后使用Box-Behnken实验优化提取工艺;以熵值法进行综合评分;建立设计空间,选取较优操作空间进行工艺验证;以最佳工艺制备15批不同产地小儿腹痛草饮片的标准汤剂,最终建立其出膏率、浸出物、薄层色谱、指纹图谱、含量及含量转移率的质量标准。结果以獐牙菜苦苷含量、龙胆苦苷含量及出膏率为关键质量属性;以浸泡时间、加水量、煎煮时间为关键工艺参数;所建立的模型差异有统计学意义;筛选的最佳工艺为:浸泡时间90 min、加水量15倍、煎煮时间30 min(第二煎20 min);出膏率21.13%~30.73%;浸出物含量在82.00%~88.00%;薄层色谱中獐牙菜苦苷斑点清晰;15批样品与参照图谱的相似度均>0.85;獐牙菜苦苷含量250.64~385.21 mg·g^(-1),转移率43.76%~77.73%;龙胆苦苷含量0.69~2.70 mg·g^(-1),转移率56.02%~105.29%。结论基于以上方法及技术筛选出小儿腹痛草标准汤剂制备工艺,可为其配方颗粒的制剂开发及质量控制提供参考。
Objective To optimize the preparation process of Swertia patens,Burk.standard decoction and establish its quality standard by using the quality by design(QbD)concept.Methods Critical Quality Attributes(CQAs)were predicted and analyzed according to the quality marker(Q-marker)theory of traditional Chinese medicine;Failure mode and effects analysis(FMEA)was used to screen critical process parameters(CPPs);The measurement method of key quality attributes was established;The extraction process was optimized by Box Behnken test after the preliminary range was determined according to the single factor test;The entropy method was used for comprehensive scoring;The design space was established and the optimal operation space for process validation was selected;Standard decoction of Swertia patens Burk in fifteen batches with different habitats were prepared with the best technology,and the quality standards for the extraction rate,extract,thin layer chromatography,fingerprint,content,and the content transfer rate were established finally.Results The key quality attributes were swertiamarin content,gentiopicrin content,and paste yield;The key process parameters were soaking time,water amount,and decocting time;The established model had statistical significance;The optimum conditions were as follows:soaking time 90 min,adding water 15 times,decocting time 30 min(second decocting 20 min);The paste yield was 21.13%-30.73%;The extract was 82.00%-88.00%;The spot of swertiamarin was clear in TLC;The similarity between each samples in 15 batches and reference atlas were>0.85%;The content of swertiamarin was 250.64-385.21 mg·g^(-1),and the transfer rate was 43.76%-77.73%;The content of gentiopicrin was 0.69-2.70 mg·g^(-1),and the transfer rate was 56.02%-105.29%.Conclusion Based on the above methods and techniques,the preparation process of Swertia patens Burk.The standard decoction was screened,which provides a reference for the preparation development and quality control of its formula granules.
作者
黄思成
李军山
张岩岩
周云涛
侯安国
黄龙
HUANG Sicheng;LI Junshan;ZHANG Yanyan;ZHOU Yuntao;HOU Anguo;HUANG Long(School of Chinese Materia Medica,Yunnan University of Chinese Medicine,Kunming 650500,China;Key Laboratory of External Drug Delivery System and Preparation Technology in University of Yunnan Province,Kunming 650500,China;Yunnan Key Laboratory of Southern Medicinal Utilization,Kunming,650500,China;Yunnan Shenwei Shipurui Pharmaceutical Co.,Ltd,Chuxiong 675000,China;Guilin Sanjin Mass Health Industry Co.,Ltd.,Guilin 541004,China)
出处
《医药导报》
CAS
北大核心
2024年第6期941-948,共8页
Herald of Medicine
基金
云南省重大科技专项计划(202102AA310027)
云南省教育厅科学研究基金项目(2023Y0453)。
