星点设计-效应面法优化柴胡和白芍配伍比例和提取工艺  

Optimization of compatibility ratio and extraction process of Radix Bupleuri and Radix Paeoniae Alba by central composite design response surface methodology

作　　者：孙小燕[1] 王爽 席啸虎[2] SUN Xiaoyan;WANG Shuang;XI Xiaohu(Department of Pharmacy,Central Hospital of China Railway 17th Bureau Group Co.,Ltd.,Taiyuan 030032,China;Department of Pharmacy,Shanxi Academy of Traditional Chinese Medicine)

机构地区：[1]中铁十七局集团有限公司中心医院药剂科,太原030032 [2]山西省中医药研究院药剂科

出　　处：《山西医科大学学报》2023年第4期521-528,共8页Journal of Shanxi Medical University

基　　金：山西省中医药研究院院级课题(202212)。

摘　　要：目的基于成分含量变化、解热抗炎活性、体外肝损伤等指标优化柴胡和白芍配伍比例和提取工艺,为临床合理用药提供数据支持。方法以柴胡皂苷a、柴胡皂苷d、柴胡皂苷c、对2,4-二硝基苯酚致热大鼠模型的解热作用、对二甲苯致小鼠耳廓肿胀抗炎作用、体外肝损伤情况为评价指标,使用星点设计效应面法进行试验,运用多指标综合评分法,分别以柴胡和白芍剂量为因素,优选其配伍比例;以乙醇浓度、溶剂倍数及提取时间为因素,优化提取工艺。根据星点设计试验结果优选的最佳配伍比例(柴胡10 g,白芍10 g)放大10倍量后进行柴胡和白芍配伍比例模型验证,按照最佳提取工艺,选取8倍量90%的乙醇,提取2次,每次90 min进行柴胡和白芍提取工艺模型验证。结果柴胡配伍白芍后可不同程度改变柴胡中指标成分含量、降低2,4-二硝基苯酚致热大鼠温度、改善二甲苯致小鼠耳廓肿胀炎症、降低对人正常肝L02细胞抑制率、降低细胞上清LDH含量。针对星点设计-配伍比例拟合的二项式方程为:Y=0.100+0.020X 1-0.207X 2+0.116X 12+0.081X 22+0.088X 1X 2,r=0.9765;针对星点设计-提取工艺拟合的二项式方程:Y′=0.636+0.111X′1+0.048X′2+0.055X′3-0.037X′12+0.028 X′22-0.088X′32-0.004X′1X′2-0.022X′1X′3-0.029X′2X′3,r=0.9231。最终确定配伍最佳比例范围为:柴胡10~15 g,白芍10~15 g;提取工艺参数范围为:乙醇浓度85%~95%,溶剂倍数7~9,提取时间80~100 min,提取2次。模型外验证结果显示3份样本偏差绝对值均小于3%,说明模型可靠。结论柴胡配伍白芍后对柴胡中指标成分提出率有一定影响,同时增强柴胡的解热抗炎活性,降低柴胡的体外肝损伤。实验优选的柴胡配伍白芍的配伍比例和提取工艺参数,可最大限度地增加柴胡活性、降低其肝损伤,为临床合理用药提供数据支持。Objective To optimize the compatibility ratio and extraction process of Radix Bupleuri and Radix Paeoniae Alba based on the content change of ingredients,antipyretic and anti-inflammatory activities,in vitro liver damage and other indicators.Methods With saikosaponin a,saikosaponin d,saikosaponin c,antipyretic effect in rat model induced by 2,4-dinitrophenol,anti-inflammatory effect in mouse auricle swelling induced by p-xylene,and in vitro liver damage as indicators,the multiple index comprehensive scoring was calculated by the central composite design response surface method to opitimize the compatibility ratio of Radix Bupleuri and Radix Paeoniae Alba.The extraction process was optimized with ethanol concentration,solvent multiple and extraction time as factors.According to the results of the central point design test,the optimal compatibility ratio(10 g of Radix Bupleuri and 10 g of Radix Paeoniae Alba)was amplified by 10 times,and then the compatibility ratio model of Radix Bupleuri and Radix Paeoniae Alba was verified.According to the optimal extraction process,the extraction process model of Radix Bupleuri and Radix Paeoniae Alba was verified under 8 times of 90%ethanol,extraction twice and 90 min per exfraction.Results The compatibility of Radix Bupleuri with Radix Paeoniae Alba affected the contents of components in Radix Bupleuri in varying degrees,reduced the temperature of 2,4-dinitrophenol-induced fever rats,improved the ear swelling and inflammation of xylene-induced mice,reduced the inhibitory rate on human normal liver L02 cells,and reduced the content of LDH in cell supernatant.The fitted binomial equation was Y=0.100+0.020X 1-0.207X 2+0.116 X 12+0.081X 22+0.088X 1X 2(r=0.9765)for star point design compatibility ratio;Y′=0.636+0.111X′1+0.048 X′2+0.055X′3-0.037X′12+0.028X′22-0.088X′32-0.004X′1X′2-0.022X′1X′3-0.029X′2X′3(r=0.9231)for star point design extraction process.The optimal proportion range of compatibility was determined as follows:Radix Bupleuri 10-15 g and Radix

关 键 词：解热抗炎 星点设计效应面法 配伍 柴胡 白芍 肝损伤 化学成分 

分 类 号：R285[医药卫生—中药学]