基于“质量源于设计”理念的复方芎芍胶囊工艺优化  

Preparation Process Optimization for Compound Xiongshao Capsules Based on QbD Theory

作　　者：姜慧婷[1] 余梅香 杨婉花[1] 夏琴[1] Jiang Huiting;Yu Meixiang;Yang Wanhua;Xia Qin(Department of Pharmacy,Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine,Shanghai 200025,China;Department of Pharmacy,Zhongshan Hospital Affiliated to Fudan University)

机构地区：[1]上海交通大学医学院附属瑞金医院药剂科,上海200025 [2]复旦大学附属中山医院药剂科

出　　处：《中国药师》2022年第8期1366-1372,共7页China Pharmacist

基　　金：上海市科委重点项目(编号:17401901100)。

摘　　要：目的:基于“质量源于设计(QbD)”理念,对复方芎芍胶囊(CXSC)的提取和纯化工艺进行优化。方法:采用正交试验法,选择正交表L_(9)(3^(4))以提取物中芍药苷、水飞蓟宾、杯苋甾酮含量和出膏率为因变量,考察提取次数、提取时间、加水倍量三因素对CXSC水提工艺的影响,确定适宜的水提取方案。建立DPN大鼠模型,造模4周后,随机分为模型对照组(DPN组)、CXSC组(0.36 g·kg^(-1))、CXSC水提取组(CXSC-W,0.66 g·kg^(-1))、CXSC水提醇沉组(CXSC-WEP,0.46 g·kg^(-1))、阳性对照依帕司他组(EP组,15 mg·kg^(-1)),灌胃给药8周后,测定运动神经传导速度(MNCV)和感觉神经传导速度(SNCV),比较水提直接浓缩法和水提醇沉法产物对DPN大鼠坐骨神经的治疗作用;进一步以有效成分(芍药苷和多糖)转移率与出膏率考察絮凝沉淀(1%壳聚糖)、乙醇沉淀、浓缩液过滤3种纯化方式,确定适宜的纯化方案。结果:正交试验优选得到的CXSC提取方案为每次加10倍量水,提取2次,每次1h,出膏率为25.0%,芍药苷含量0.71%,水飞蓟宾含量0.067%,杯苋甾酮含量0.007 3%。药效学试验发现,与DPN模型组相比,CXSC-W组MNCV显著提高(P<0.05),而CXSC-WEP组MNCV无显著变化(P>0.05),即水提直接浓缩法纯化产物的药效优于水提醇沉法。纯化工艺研究中,优选得到的CXSC纯化处理方法为浓缩至原提取液1/4体积左右,静置24 h通过离心去除沉淀,取上清液继续浓缩至规定密度,芍药苷和多糖含量较高,出膏率较低。结论:所建立的基于QbD理念研究方法,兼顾工艺可行性和制剂疗效。考察并确立了保证较高有效成分含量和较低出膏率的稳健可靠的提取工艺和纯化工艺,为其制剂的质量稳定、安全、有效提供依据。Objective: To optimize the extraction process and the purification process of compound Xiongshao capsules(CXSC) based on the theory of quality by design(QbD), so as to promote the stable process, reliable quality, safe and effective use of CXSC. Methods: L_(9)(3^(4)) orthogonal table was selected to investigate the effects of different levels of extracting times(A), extracting time(B) and water addition(C) on the water extraction process of CXSC. The contents of paeoniflorin, silybin and cyasterone in the orthogonal samples were detected to investigate the effects of the extraction process. The content and yield rate of solid matters were used as dependent variables to analyze the variance of the results of orthogonal design to obtain the best extraction scheme. The diabetic peripheral neuropathy(DPN) rat model induced by streptozotocin was established. After 4 weeks of modeling, model rats were randomly divided into 5 groups: model control group(DPN group), CXSC group(0.36 g·kg^(-1)), CXSC water extraction group(CXSC-W, 0.66 g·kg^(-1)), CXSC water extraction and ethanol precipitation group(CSXC-WEP, 0.46 g·kg^(-1)), epalrestat positive control group(EP group, 15 mg·kg^(-1)). After 8 weeks of intragastric administration, the motor nerve conduction velocity(MNCV) and sensory nerve conduction velocity(SNCV) were measured to evaluate the therapeutic effects of purified products on sciatic nerve of DPN rats. Different purification methods including flocculation sedimentation(1% chitosan), ethanol precipitation and concentrate filtration were further investigated by using the transfer of effective components(paeoniflorin and polysaccharide) and yield rate of solid matters as the indexes. Results: The optimized extraction process was as follows: adding 10-fold amount of water, and extracted twice with 1 h for each time, and the yield rate of solid matters was 25.0%. The content of paeoniflorin in the solid matters was 0.71%, silibinin was 0.067%, and cyasterone was 0.0073%. Pharmacodynamic test showed that compared

关 键 词：复方芎芍胶囊 糖尿病周围神经病变 提取工艺 纯化工艺 药效学 

分 类 号：R283.6[医药卫生—中药学]