木犀草素与哌嗪共晶的表征及初步药动学研究  

Characterization and Preliminary Pharmacokinetics Study of Luteolin and Piperazine Cocrystal

作　　者：燕柳艳 生立嵩 宋俊科[1] 杨德智[2] 张丽[2] 吕扬[2] 王守宝[1] 杜冠华 YAN Liuyan;SHENG Lisong;SONG Junke;YANG Dezhi;ZHANG Li;LYU Yang;WANG Shoubao;DU Guanhua(Beijing Key Laboratory of Drug Target Research and New Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100050 China;Beijing Key Laboratory of Crystalline Drug Research,Institute of Materia Medica,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100050,China;Chinese Medicine Preparation Laboratory, Institute of Traditional Chinese Medicine,Shandong Institute of Traditional Chinese Medicine,Jinan 250014,China)

机构地区：[1]北京协和医学院、中国医学科学院药物研究所药物靶点研究与新药筛选北京市重点实验室,北京100050 [2]北京协和医学院、中国医学科学院药物研究所晶型药物研究北京市重点实验室,北京100050 [3]山东省中医药研究院中药制剂研究所中药制剂研究室,济南250014

出　　处：《医药导报》2022年第5期621-625,共5页Herald of Medicine

基　　金：国家重点研发计划(2018YFC0311003);海洋药物与生物制品功能实验室开放基金资助项目(LMDBKF201804)。

摘　　要：目的研究木犀草素与哌嗪共晶的制备与表征,体外溶解性以及大鼠体内药动学,并与二者同比例物理混合物进行对比。方法对共晶以及物理混合物进行粉末X射线衍射(PXRD)和差示扫描量热(DSC)分析,采用高效液相色谱法检测其体外溶解性,采用高效液相色谱-串联质谱技术测定大鼠灌胃给药的血药浓度,比较主要药动学参数的差异。结果共晶与木犀草素的PXRD、DSC等方法检测结果存在明显差异,在十二烷基硫酸钠溶液中的溶解度较物理混合物提高39%。大鼠灌胃给予共晶和物理混合物后,共晶的达峰时间和体内滞留时间明显缩短,药物浓度-时间曲线下面积增加。结论共晶改善了木犀草素溶解度和体内生物利用度,提高了木犀草素的成药性。Objective To prepare,and characterize the cocrystal of luteolin and piperazine,and to compare the solubility and pharmacokinetics of luteolin cocrystal and mixture in vitro.Methods The powder X-ray diffraction(PXRD)and differential scanning calorimetry(DSC)were used to characterize the cocrystal and physical mixture.The in vitro solubility of luteolin was determined by the method of HPLC.The plasma concentration of luteolin was determined by liquid chromatography combined with mass spectrum(LC-MS).Results There were obvious differences in the results of PXRD and DSC between the cocrystal and luteolin.The solubility of the cocrystal in SDS solution was higher than that of the physical mixture by 39%.The primary pharmacokinetic study on the rats showed that,as compared to the physical mixture,the cocrystal presented shorter time reaching to peak and retention time,and increased the area under the drug concentration-time curve after intragastric administration.Conclusion The cocrystal improves the solubility and bioavailability of luteolin,indicating that a better druggability of luteolin.

关 键 词：木犀草素 哌嗪 共晶 药动学 生物利用度 

分 类 号：R282.71[医药卫生—中药学] R943[医药卫生—中医学]