Box-Behnken设计结合通量衰减探索热毒宁注射液醇沉中间体的纳滤分离规律  

Exploration of nanofiltration conditions for separation of alcohol precipitation liquid during preparation of Reduning Injection by Box-Behnken design combined with flux attenuation

作　　者：李存玉[1,2,3,4,5] 蒋佳丽 张永拓 邹雨岑 支兴蕾 彭国平[1,2,3,4,5] LI Cun-yu;JIANG Jia-li;ZHANG Yong-tuo;ZOU Yu-cen;ZHI Xing-lei;PENG Guo-ping(College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Kanion Parmaceutical Co.,Ltd.,Lianyungang 222001,China;State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process,Lianyungang 222001,China;Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing 210023,China;Jiangsu Province Engineering Research Center of Classical Prescription,Nanjing 210023,China)

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏康缘药业股份有限公司,江苏连云港222001 [3]中药制药过程新技术国家重点实验室,江苏连云港222001 [4]江苏省中药资源产业化过程协同创新中心,江苏南京210023 [5]江苏省经典名方工程研究中心,江苏南京210023

出　　处：《中国中药杂志》2022年第7期1881-1887,共7页China Journal of Chinese Materia Medica

基　　金：江苏省自然科学基金面上项目(BK20211303);国家自然科学基金项目(82074006);中药制药过程新技术国家重点实验室开放基金项目(SKL2020Z0101);2021年国家级大学生创新创业训练计划项目(202110315042)。

摘　　要：该文采用Box-Behnken设计结合通量衰减技术,探索热毒宁注射液醇沉中间体的纳滤分离规律,明确高浓度乙醇溶液环境的纳滤分离适用性。结果表明,建立的纳滤分离数学模型成立,可以用于分析考察因素与成分分离行为的内在关系。其中,纳滤膜相对截留分子质量、pH对绿原酸、3,5-二-O-咖啡酰奎宁酸、4,5-二-O-咖啡酰奎宁酸的分离行为影响分别符合孔径筛分和电荷效应原理,跨膜压力差带来的浓差极化效应降低成分截留率,乙醇引起膜面溶胀导致膜通量衰减、有效分离孔径下降,其中绿原酸和4,5-二-O-咖啡酰奎宁酸对pH和乙醇浓度的敏感度强于3,5-二-O-咖啡酰奎宁酸。成分结构与纳滤分离因素存在一定相关性,且分离规律是电荷效应、孔径筛分、浓差极化、孔道位阻等多种效应综合的结果。This study employed Box-Behnken design combined with flux attenuation to explore the nanofiltration conditions for separation of alcohol precipitation liquid during the preparation of Reduning Injection and discussed the applicability of nanofiltration in the separation of the liquid with high-concentration ethanol. The effects of nanofiltration molecular weight cut-off(MWCO) and pH on the rejection of chlorogenic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid were consistent with the principles of pore size sieving and charge effect, respectively. The rejection of the three phenolic acids was reduced by concentration polarization effect caused by trans-membrane pressure(TMP). The swelling of membrane surface decreased the pore size and membrane flux for effective separation. Chlorogenic acid and 4,5-dicaffeoylquinic acid were more sensitive to pH and ethanol concentration than 3,5-dicaffeoylquinic acid. A certain correlation existed between the compound structure and the separation factors of nanofiltration, and the separation rules were associated with the comprehensive effect of charge effect, pore size sieving, concentration polarization, steric hindrance and so on.

关 键 词：热毒宁注射液 纳滤 绿原酸 3 5-二-O-咖啡酰奎宁酸 4 5-二-O-咖啡酰奎宁酸 

分 类 号：R284[医药卫生—中药学] TQ461[医药卫生—中医学]