富马酸丙酚替诺福韦的晶型研究  

Study on crystal structure of propofol tenofovir fumarate

作　　者：常珍 安明 祝江业 苏亚军 况斌 CHANG Zhen;AN Ming;ZHU Jiang-ye;SU Ya-jun;KUANG Bin(Beijing Horicin Biotechnology Co.,Ltd.,Beijing 100023,China)

机构地区：[1]北京华睿鼎信科技有限公司,100023

出　　处：《中国医药生物技术》2023年第3期219-224,共6页Chinese Medicinal Biotechnology

基　　金：“重大新药创制”国家科技重大专项(2019ZX09302019)。

摘　　要：目的研究富马酸丙酚替诺福韦的晶型并明确其成盐比例。方法以丙酚替诺福韦为起始物料,与不同比例富马酸成盐,得到两种不同晶型的目标化合物。经熔点测定、X-射线粉末衍射、X-射线单晶衍射等方法表征晶体结构。结果得到两种不同晶型的目标化合物1和3,其中化合物1的熔点为129.1~131.4℃,化合物3的熔点为120.1~121.0℃。经X-射线粉末衍射检测,前者特征峰2θ为6.757°、8.399°、10.842°、11.888°、15.646°、16.096°、19.998°、20.574°、22.893°、26.401°;后者特征峰2θ为5.155°、10.347°、10.884°、19.424°、21.065°、26.444°。经X-射线单晶衍射检测,确定化合物1是由1分子富马酸和2分子丙酚替诺福韦组成,化合物3是由1分子富马酸和1分子丙酚替诺福韦组成,并对化合物1的晶型进行了确证。结论该方法操作简便,收率高,产物晶型稳定。化合物1作为原料可满足工业化生产要求。Objective To study the crystal form of tenofovir propofol fumarate and determine its salt formation ratio.Methods Tenofovir propofol was used as the starting material and salted with fumarate to obtain two target compounds with different crystal forms.The crystal structure was characterized by melting point,X-ray powder diffraction,and X-ray single crystal diffraction.Results The melting point of propofol tenofovir fumarate(1:2)was 129.1-131.4℃,and the melting point of propofol tenofovir fumarate(1:1)was 120.1-121.0℃,which was consistent with the literature reports.The characteristic peak 2θof the former was 6.757°,8.399°,10.842°,11.888°,15.646°,16.096°,19.998°,20.574°,22.893°and 26.401°.The latter characteristic peaks 2θwere 5.155°,10.347°,10.884°,19.424°,21.065°and 26.444°.It was confirmed by X-ray single crystal diffraction that tenofovir propofol fumarate(1:2)was composed of 1 molecule fumarate and 2 molecules tenofovir propofol.Conclusion The method is easy to operate,the yield is high,the product is stable,and it is suitable for industrial production.

关 键 词：富马酸丙酚替诺福韦 晶体结构 X-射线单晶衍射 

分 类 号：R943[医药卫生—药剂学]