星点设计-效应面优化苦参总生物碱组分磷脂复合物研究  

Optimization of Preparation of Total Alkaloids from Sophora flavenscens Phospholipid Complex by Central Composite Design-Response Surface Method

作　　者：杨志欣[1] 王海威[1] 张文君[2] 李霞[1] 程静 王莹[1] 侯立强[3] YANG Zhi-xin;WANG Hai-wei;ZHANG Wen-jun;LI Xia;CHENG Jing;WANG Ying;HOU Li-qiang(College of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China;School of Pharmacy,Harbin Universi-ty of Commerce,Harbin 150076,China;The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150001,China)

机构地区：[1]黑龙江中医药大学药学院,黑龙江哈尔滨150040 [2]哈尔滨商业大学药学院,黑龙江哈尔滨150076 [3]黑龙江中医药大学附属第二医院,黑龙江哈尔滨150001

出　　处：《中药材》2018年第3期660-664,共5页Journal of Chinese Medicinal Materials

基　　金：黑龙江省自然科学基金(H2016057;H2017066);国家教育部春晖计划(Z2008-1-15016);黑龙江中医药大学"优秀创新人才支持计划"项目(2012)

摘　　要：目的:优化苦参总生物碱组分磷脂复合物(TA-PC)的工艺,研究其理化性质。方法:采用溶剂挥发法制备TA-PC,单因素考察反应溶剂、反应温度、药物质量浓度、反应时间、药脂比等对磷脂复合率的影响;星点设计-效应面法优化处方及工艺。HPLC法测定苦参总生物碱中氧化苦参碱、氧化槐果碱、苦参碱、槐果碱的含量,并以4个生物碱含量为指标考察TA-PC的溶解性、油水分配系数,电镜分析水中分布的形态及大小,红外图谱研究药物与磷脂结合方式。结果:最优条件为:乙醇为反应溶剂,药物与大豆磷脂投料比2.5∶1,药物质量浓度3.0 mg/mL,反应温度为40℃,反应时间2 h。复合率达95.27%±0.65%,与预测值偏差<5.0%;IR验证了所形成的磷脂复合物为一种弱的相互作用,未发生化学变化;水中溶解度明显降低,油水分配系数明显增加。结论:星点设计-效应面法成功制备了TA-PC,工艺稳定可行,提高了TA的脂溶性,为其进一步开发制剂奠定基础。Objective:To optimize the preparation of total alkaloids from Sophora flavenscens(TA)phospholipid complex(TA-PC)by central composite design-response surface method,and study its physical and chemical properties.Methods:TA-PC was prepared by using solvent evaporation method,five factors including reaction solvent,reaction temperature,mass concentration,reaction time and ratio of reactants on this reaction of the drug were investigated and optimized the preparation of TA-PC by central composite designresponse surface method.The content of matrine,oxymatrine,oxysophocarpine and sophocarpine in total alkaloids of Sophora flavenscens was determined by HPLC.The solubility,oil and water partition coefficient of TA-PC were investigated with four alkaloids′ content,the morphology and size of water distribution were anlyzed by electron microscopy;the combination of drugs and phospholipids were detected by infrared spectrum.Results:The optimal process conditions were as follows,the solvent was ethanol,the ratio of TA and PC was 2.5∶1,the mass concentration was 3 mg/mL,the reaction temperature was 40 ℃,the reaction time was 2 h.The complexing rate was 95.27%±0.65%,it was less than 5% with the predicted deviation.IR confirmed that the formed phospholipid complex was a weak interaction with no chemical change,and the solubility in the octyl alcohol was higher than the original drug.Conclusion:TA-PC is successfully developed by the optimized process,the method enhances the solubility in octyl alcohol,which provide the reference for the further development and utilization of Chinese materia medica preparation.

关 键 词：苦参总生物碱 磷脂复合物 油水分配系数 星点设计-效应面法 

分 类 号：R283.6[医药卫生—中药学]