目的 研究新型鈉–葡萄糖協(xié)同轉(zhuǎn)運(yùn)蛋白2抑制劑tianagliflozin與L-脯氨酸的共結(jié)晶，制備一種穩(wěn)定的可供藥用的共結(jié)晶。方法 在乙醇中共結(jié)晶制備tianagliflozin與L-脯氨酸的共結(jié)晶，并采用核磁共振氫譜、粉末X衍射、熱重/差熱分析及紅外光譜測定共結(jié)晶物的特征。初步考察了共結(jié)晶對(duì)光、溫度和濕度的穩(wěn)定性。結(jié)果 制備了tianagliflozin與L-脯氨酸穩(wěn)定的1∶1共結(jié)晶，初步穩(wěn)定性考察表明該共結(jié)晶對(duì)光照、高溫和低中濕穩(wěn)定，高濕條件下發(fā)生分解。結(jié)論 tianagliflozin與L-脯氨酸的共結(jié)晶在穩(wěn)定性和制備重現(xiàn)性方面較好，為其成藥性研究提供了參考。

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, high temperature, and low to medium moisture, but unstable to high moisture, which could decompose the cocrystallization to its individual components. Conclusion The cocrystallization of tianagliflozin and L-proline is stable and reproducible, which provide reference for its druggablitiy.

國家自然科學(xué)基金資助項(xiàng)目(21302141)；天津市科技計(jì)劃項(xiàng)目(10ZCKFSH01300)