木犀草素药-药共晶的制备、性质及生物利用度研究  

Preparation,properties and bioavailability of drug-drug cocrystal of luteolin

作　　者：李静萍 陈新科 蒋才武[1] 邓刚[1] LI Jing-ping;CHEN Xin-ke;JIANG Cai-wu;DENG Gang(Guangxi University of Chinese Medicine,Guangxi Key Laboratory of Zhuang and Yao Medicine,Nanning 530200)

机构地区：[1]广西中医药大学,广西壮瑶药重点实验室,南宁530200

出　　处：《中南药学》2024年第12期3215-3220,共6页Central South Pharmacy

基　　金：广西自然科学基金面上项目(No.2023GXNSFAA026292);广西壮瑶药重点实验室开放课题(No.桂科基字[2014]32号)。

摘　　要：目的 合成木犀草素-5-氟尿嘧啶(LU-5-FU)和木犀草素-烟酸(LU-NA)共晶,增加木犀草素的水溶性及其生物利用度。方法 通过湿法研磨法和溶剂法设计合成两个药物-药物共晶,采用粉末X射线衍射、红外光谱、差热分析和磁共振谱等技术对其进行表征,利用高效液相色谱法研究其在pH 1.2盐酸溶液中的体外溶出度,并在大鼠体内进行药动学研究,计算主要药动学参数。结果 LU-5-FU共晶和LU-NA共晶出现了特征光谱;在pH 1.2盐酸溶液中最大溶出度分别提高2320%和300%;药动学实验中,LU-5-FU共晶和LU-NA共晶的最大血药浓度(C_(max))、曲线下面积(AUC_(0~t))与木犀草素原料药相比,差异有统计学意义(P<0.05),共晶的C_(max)与AUC_(0~t)对比原料药有显著提高,其相对生物利用度分别为850%和560%。结论 合成了两个化学计量比为1∶1的目标共晶,它们能够显著提高木犀草素的体外溶出度和体内生物利用度。Objective To synthesize luteolin-5-fluorouracil (LU-5-FU cocrystal) and luteolin-nicotinic acid (LU-NA cocrystal) cocrystals and improve their water solubility and bioavailability.Methods Two drug-drug cocrystals were designed and synthesized by wet grinding and solvent method.They were characterized by powder X-ray diffraction,infrared spectroscopy,differential thermal analysis and nuclear magnetic resonance spectroscopy.Their in vitro dissolution in pH 1.2 hydrochloric acid solution was determined by high performance liquid chromatography.The main pharmacokinetic parameters of rats were calculated.Results The characteristic spectra of LU-5-FU cocrystal and LU-NA cocrystal appeared.The maximum dissolution rate in the pH 1.2 hydrochloric acid solution increased by 2320% and 300%,respectively.In the pharmacokinetic experiments,there was a significant difference (P<0.05) in the maximum blood drug concentration (C_(max)) and area under the curve (AUC_(0~t)) of LU-5-FU cocrystal and LU-NA cocrystal as compared with the raw material of luteolin.The C_(max) and AUC_(0~t) were greatly improved as compared with the raw material of luteolin,with relative bioavailability at 850% and 560%,respectively.Conclusion Two target cocrystals with a stoichiometric ratio of 1∶1 are synthesized,whose in vitro dissolution and in vivo bioavailability of luteolin have been improved.

关 键 词：木犀草素 5-氟尿嘧啶 烟酸 药物共晶 溶出度 生物利用度 

分 类 号：R944[医药卫生—药剂学]