两种布洛芬共晶与牛血清白蛋白作用机制研究  

Mechanism of Interaction Between Two Ibuprofen Co-Crystals and Bovine Serum Albumin

作　　者：范莹 张帅华 杨钊 FAN Ying;ZHANG Shuaihua;YANG Zhao(Qingdao Special Servicemen Recuperation Center of PLA Navy,Qingdao,Shandong,China 266071;School of Pharmacy,Shandong University,Jinan,Shandong,China 250012;Food and Drug Inspection Institute of Qingdao,Qingdao,Shandong,China 266071)

机构地区：[1]中国人民解放军海军青岛特勤疗养中心,山东青岛266071 [2]山东大学药学院,山东济南250012 [3]山东省青岛市食品药品检验研究院,山东青岛266071

出　　处：《中国药业》2022年第13期53-57,共5页China Pharmaceuticals

基　　金：国家科技重大专项-重大新药创制课题[2017ZX09101001006]。

摘　　要：目的探讨布洛芬-异烟酰胺(IBU-INA)和布洛芬-2-吡啶甲酰胺(IBU-2PA)2种布洛芬共晶与牛血清白蛋白(BSA)的相互作用机制。方法采用荧光光谱法和紫外吸收光谱法研究不同温度(32℃和40℃)下IBU-INA和IBU-2PA与BSA的猝灭作用,并阐明其作用机制。结果IBU-INA和IBU-2PA均能有效猝灭BSA产生的内源性荧光,猝灭机制属静态猝灭。32℃时,布洛芬与BSA的结合常数为1545 L/mol,IBU-INA和IBU-2PA与BSA的结合常数分别为2074 L/mol和1303 L/mol。IBU-INA和IBU-2PA与BSA的主要作用力类型为氢键和范德华力。根据Förster理论,测得IBU-INA和IBU-2PA与BSA的相互作用距离分别为1.22 nm和1.31 nm,可判断发生了非辐射能量转移。结论布洛芬形成共晶后不会影响布洛芬与血浆蛋白的结合。Objective To investigate the mechanism of interaction between two ibuprofen co-crystals[ibuprofen-isonicotinamide(IBU-INA)and ibuprofen-2-picolinamide(IBU-2PA)]with bovine serum albumin(BSA).Methods The quenching effects of IBU-INA,IBU-2PA with BSA at different temperatures(32℃and 40℃)were studied by the fluorescence spectroscopy and ultraviolet absorption spectroscopy,and the mechanism was elucidated.Results IBU-INA and IBU-2PA could effectively quench the endogenous fluorescence induced by BSA,and the quenching mechanism was static quenching.At 32℃,the binding constant of ibuprofen to BSA was 1545 L/mol,and the binding constants of IBU-INA and IBU-2PA to BSA were 2074 L/mol and 1303 L/mol,respectively.The main force types of IBU-INA,IBU-2PA with BSA were hydrogen bond and van der Waals.According to the Förster theory,the interaction distances of IBU-INA and IBU-2PA with BSA was 1.22 nm and 1.31 nm respectively,indicating that non-radiative energy transfer occurred.Conclusion The formation of ibuprofen co-crystals will not affect the binding between ibuprofen and plasma proteins.

关 键 词：布洛芬 布洛芬-异烟酰胺 布洛芬-2-吡啶甲酰胺 牛血清白蛋白 荧光光谱法 紫外吸收光谱法 作用机制 

分 类 号：R965[医药卫生—药理学] R971.1[医药卫生—药学]