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| 离子液体在药物晶体工程中的应用 | |
| 引用本文： | 尚泽仁,胡卫国,汤伟伟,贾丽娜,李鸣晨,赵燕晓,魏宁,龚俊波. 离子液体在药物晶体工程中的应用[J]. 化工进展, 2019, 38(5): 2389-2401. DOI: 10.16085/j.issn.1000-6613.2018-1482 |
| 作者姓名： | 尚泽仁 胡卫国 汤伟伟 贾丽娜 李鸣晨 赵燕晓 魏宁 龚俊波 |
| 作者单位： | 天津大学化工学院国家工业结晶工程技术研究中心,天津300072;天津化学化工协同创新中心,天津300072;现代药物传递及功能高效化天津市重点实验室,天津300072;天津大学化工学院国家工业结晶工程技术研究中心,天津300072;天津化学化工协同创新中心,天津300072;现代药物传递及功能高效化天津市重点实验室,天津300072;华北制药股份有限公司,河北石家庄050015 |
| 基金项目： | 国家自然科学基金(21676179、91634117、81361140344);国家科技重大专项(2017ZX07402003、2017ZX09101001);天津市科技计划(15JCZDJC33200) |
| 摘 要： | 近年来,使用离子液体替代传统溶剂参与调节结晶过程中的各种相互作用以获得新颖的晶体结构是药物晶体工程的研究前沿。研究人员在离子液体体系中得到了使用传统溶剂无法制得的药物晶型或晶习并进行了相应机理的初步探索。针对离子液体在药物晶体工程中的应用,本文从离子液体的组成和性质及其在药物增溶、药物晶型及晶习的调控和药物共晶及盐的制备几方面展开,首次综述了相关研究成果并基于红外光谱、分子动力学模拟等手段从相互作用的角度对机理进行分析,其中氢键和范德华力相互作用起到了重要影响。最后针对该领域现存的问题如离子液体的选择处于盲筛阶段,相应机理研究缺乏和应用范围不广泛,指出建立系统的离子液体选择标准和深入研究机理是未来的主要研究方向。 |
| 关 键 词： | 离子液体 药物晶体工程 增溶 分子间相互作用 |
| 收稿时间： | 2018-07-17 |
Application of ionic liquids in pharmaceutical crystal engineering |
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| Zeren SHANG,Weiguo HU,Weiwei TANG,Lina JIA,Mingchen LI,Yanxiao ZHAO,Ning WEI,Junbo GONG. Application of ionic liquids in pharmaceutical crystal engineering[J]. Chemical Industry and Engineering Progress, 2019, 38(5): 2389-2401. DOI: 10.16085/j.issn.1000-6613.2018-1482 | |
| Authors: | Zeren SHANG Weiguo HU Weiwei TANG Lina JIA Mingchen LI Yanxiao ZHAO Ning WEI Junbo GONG |
| Affiliation: | 1. National Engineering Research Center of Industry Crystallization Technology,School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072, China 2. Collaborative Innovation Center of Chemical Science and Engineering Tianjin,Tianjin 300072, China 3. Key Laboratory of Modern Drug Delivery and High Efficiency in Tianjin University,Tianjin 300072, China 4. North China Pharmaceutical Company Ltd. ,Shijiazhuang 050015,Hebei,China |
| Abstract: | In recent years, using ionic liquids instead of traditional solvents to regurate various interactions in the crystallization process to obtain novel crystal structures is the research front of pharmaceutical crystal engineering. In ionic liquid systems, researchers have produced new pharmaceutical crystal forms or crystal habits which were not achievable with traditional solvents, and the corresponding mechanisms have also been studied preliminarily. In this review, the achievements of the use of ionic liquids in pharmaceutical crystal engineering were summaried, including the compositions and properties of ionic liquids, pharmaceutical solubilization, pharmaceutical polymorphs, crystal habits and formation of pharmaceutical co-crystals, and salts directed by ionic liquids. According to the intermolecular interaction, the mechanisms of these achievements were analyzed by infrared spectroscopy, molecular dynamics simulation and other means, in which hydrogen bond and van der Waals interaction have played an important role. The existing problems in this field include the selection of ionic liquids, the corresponding mechanism, and practical applications. The selection criteria for ionic liquids and in-depth mechanism research shall be the main research direction in the future. |
| Keywords: | ionic liquid pharmaceutical crystal engineering solubilization intermolecular interaction |
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