复方新诺明有效成分的晶体结构及共晶研究  

Research on the co-crystal and structures of the effective constituents in radonil

作　　者：杨洁[1] 刘浩 李姗姗 郭燕 陈强[3] 梅其炳 武祥龙 YANG Jie;LIU Hao;LI Shanshan;GUO Yan;CHEN Qiang;MEI Qibing;WU Xianglong(Shaanxi Academy of Traditional Chinese Medicine,Xi'an,Shaanxi 710003,China;Key Laboratory for Space Bioscience and Biotechnology,School of Life Sciences,Northwestern Polytechnical University,Xi′an,Shaanxi 710072,China;School of Materials Science and Engineering,Northwestern Polytechnical University,Xi′an,Shaanxi 710072,China)

机构地区：[1]陕西省中医药研究院,陕西西安710003 [2]西北工业大学生命学院空间生物实验模拟技术重点实验室,陕西西安710072 [3]西北工业大学材料学院,陕西西安710072

出　　处：《安徽医药》2021年第11期2136-2139,I0001,共5页Anhui Medical and Pharmaceutical Journal

基　　金：国家自然科学基金(31800802);陕西省自然科学基金(2019JM-152);研究生创新种子基金(CX2020258);大学生创新创业训练计划项目(S201910699420,S202010699055)。

摘　　要：目的研究复方新诺明中有效成分磺胺甲[口恶]唑(SMZ)的单晶结构,研究其与甲氧苄啶(TMP)的共晶现象,为开发共晶新剂型提供实验支持。方法采用加溶剂研磨法制备SMZ和TMP的共晶粉末,利用反射法测定红外光谱,采用差示扫描量热法(DSC)测定熔点,通过粉末X射线衍射(PXRD)研究晶型。通过溶剂挥发法得到SMZ的单晶,利用X射线单晶衍射仪测定其晶体结构。结果 SMZ的单晶属于单斜晶系,空间点群为C2/c,晶胞参数a=1.620 9(10)nm,b=0.552 7(3)nm,c=2.595 5(16)nm,每个晶胞中有8个分子。共晶粉末的熔点为187.78℃,介于SMZ的熔点170.92℃和TMP的熔点201.96℃之间。与单独组分相比较,红外图谱的指纹区发生明显变化,PXRD产生新的X射线粉末衍射峰。结论 SMZ的单晶属于E型结构,SMZ和TMP通过研磨可以形成共晶,共晶现象引起红外、熔点和衍射峰的明显变化,研究结果为开发药物共晶新剂型提供实验基础。Objective The crystal structure of sulfamethoxazole which was the main effective constituent of Radonil was obtained and researched.The co-crystal phenomena between sulfamethoxazole(SMZ)and trimethoprim(TMP)were studied to obtain more exper‐imental data for developing new dosage forms.Methods The co-crystals of SMZ and TMP were prepared by trituration with solvent.The infrared spectroscopy,melting point and crystal form of SMZ,TMP,and co-crystals were investigated by attenuated total reflec‐tance FT-IR,differential scanning calorimetry and powder X-ray diffraction.The single crystal of SMZ was obtained from methanol by solvent evaporation method.The crystal structure of SMZ was tested by X-ray single crystal diffractometer.Results The crystal of SMZ was monoclinic,space group C2/c,with a=1.6209(10)nm,b=0.5527(3)nm,c=2.5955(16)nm,eight molecular in one cell unit.The melting point of the co-crystal was 187.78℃which was between the SMZ(170.92℃)and the TMP(201.96℃).Comparing with the SMZ and TMP,the FT-IR of co-crystals in the molecular fingerprint region had some significant difference.The new X-ray powder dif‐fraction peaks were found from the co-crystals.Conclusion The configuration of SMZ single crystal structure was E conformation.The co-crystal can be obtained by trituration.Some significant difference in FT-IR,melting point and diffraction peaks were introduced by co-crystal phenomenon.These results will provide an experimental basis for the development of new drug co-crystals dosage forms.

关 键 词：甲氧苄氨嘧啶 磺胺甲[口恶]唑复方合剂 粉末衍射 晶体结构 共晶 抗菌药物 

分 类 号：R927.1[医药卫生—药学]