tianagliflozin与L-脯氨酸的共结晶研究.PDFVIP

• 838 • 现代药物与临床 Drugs Clinic 第 28 卷 第 6 期 2013 年 11 月 tianagliflozin 与L-脯氨酸的共结晶研究 1 1, 2 1, 2 2 1 1 1* 刘冰妮 ，徐华强 ，张铃钰 ，王建武 ，徐为人 ，汤立达 ，赵桂龙 1. 天津药物研究院 天津市新药设计与发现重点实验室，天津 300193 2. 山东大学 化学与化工学院，山东 济南 250100 摘 要：目的 研究新型钠–葡萄糖协同转运蛋白 2 抑制剂 tianagliflozin 与L-脯氨酸的共结晶，制备一种稳定的可供药用的 共结晶。方法 在乙醇中共结晶制备 tianagliflozin 与 L-脯氨酸的共结晶，并采用核磁共振氢谱、粉末 X 衍射、热重/差热分 析及红外光谱测定共结晶物的特征。初步考察了共结晶对光、温度和湿度的稳定性。结果 制备了 tianagliflozin 与L-脯氨酸 稳定的 1 ∶1 共结晶，初步稳定性考察表明该共结晶对光照、高温和低中湿稳定，高湿条件下发生分解。结论 tianagliflozin 与L-脯氨酸的共结晶在稳定性和制备重现性方面较好，为其成药性研究提供了参考。 关键词：tianagliflozin ；L-脯氨酸；共结晶；成药性 中图分类号：R917 文献标志码：A 文章编号：1674 - 5515(2013)06 - 0838 - 04 DOI: 10.7501/j.issn.1674-5515.2013.06.006 Cocrystallization of tianagliflozin and L-proline 1 1, 2 1, 2 2 1 1 1 LIU Bing-ni , XU Hua-qiang , ZHANG Ling-yu , WANG Jian-wu , XU Wei-ren , TANG Li-da , ZHAO Gui-long 1. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China 2. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China Abstract: Objective To investigate the cocrystallization of tianagliflozin, a new inhibitor on sodium-dependent glucose co-transporter 2, and L-proline and to prepare a stable modality of medicinal cocrystallization. Methods The cocrystallization of tianagliflozin and L-proline was prepared from ethanol cocrystallization, and characterized by 1H-NMR, PXRD, TG/DTA, and IR methods. Preliminary stability tests of cocrystallization to light, temperature, and moisture were performed. Results The cocrystallization of tianagliflozin and L-proline in a molecular ratio of 1 ∶1 was prepared. The stability test demonstrated that the cocrystallization was stable to light,