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新型阳离子环糊精衍生物手性固定相的制备及其在手性药物拆分中的应用研究

新型阳离子环糊精衍生物手性固定相的制备及其在手性药物拆分中的应用研究
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  • 批准号:81703467
  • 批准年度: 2017年
  • 学科分类:药物分析(H3010) |
  • 项目负责人:俞嘉
  • 负责人职称:讲师
  • 依托单位:沈阳药科大学
  • 资助金额:20.1万元
  • 项目类别:青年科学基金项目
  • 研究期限:2018年01月01日 至 2020年12月31日
  • 中文关键词: 阳离子;环糊精;衍生物;固定相;手性药物
  • 英文关键词:Cationic cyclodextrin;Chiral stationary phase;Chiral drugs;Enantioseparation;High performance liquid

项目摘要

中文摘要

手性药物拆分是药物分析领域中的研究热点与难点,在手性药物合成、药效、药代动力学及质控研究中显得尤为重要。基于手性固定相的高效液相色谱法是分离或检测手性药物对映体的一个非常有效的方法。手性固定相是实现拆分的核心与关键,根据预分离化合物的结构特点而有目的地制备分离效能高、性能稳定的新型手性固定相具有重大意义。环糊精及其衍生物具备强大的手性选择性与拆分能力,在手性固定相的制备领域占有重要地位。本项目拟设计合成一系列针对酸性或中性药物表现出较好分离能力的阳离子环糊精手性固定相,研究其分离能力并总结分离规律;利用分子印迹固相萃取技术对复杂生物样品中手性药物进行萃取与富集,开展手性药物立体选择性药动学研究;结合光谱分析和分子模拟技术判断主客体分子之间的作用类型和结合位点,在分子水平阐明分离机理。本项目的实施,对于丰富手性固定相的种类,提高手性药物的研发水平,具有重要意义和应用价值。

英文摘要

Enantioseparation of chiral drug is a hot and difficult research subject in pharmaceutical analysis field, especially in the area of pharmaceutical enantiomers synthesis, pharmacokinetic and pharmacodynamic study of single isomer, and chiral drugs quality control. High performance liquid chromatography method based on chiral stationary phase has been proved to be an effective and ideal approach in enantioseparation, in which the core and key section is the proper chiral stationary phase. With the aim of separating the analyte according to the analyte's structure and property, to design and synthesis the new chiral stationary phases with good separation performance and long service usage is endowed with great importance and significance. Cyclodextrin and its derivatives showed great chiral separation ability and gained much more attraction in chiral stationary phase synthesis field. In the present project, we design and synthesis a series of cationic cyclodextrin derivatives which are suitable and effective in acidic and neutral chiral drug enantioseparation, and then chemical bonded to gel silica to obtain the new chiral stationary phases. Subsequently, the performance and enantioseparation ability of the new chiral stationary phases will be investigated systematically and the separation regularities will be summarized. On the basis of good enantioseparation and by the aid of the molecularly imprinted solid-phase extraction technology with great extraction and preconcentration ability, the method will be further utilized for application of stereo selective pharmacokinetic study. With the help of spectrum analysis and computer modeling technique the chiral separation mechanism according to the host-guest interaction mode and inclusion binding site between cyclodextrin and chiral drug will be studied at the molecular level. Therefore, this project will provide and establish new models and design ideas in chiral stationary phase synthesis, resulting in great scientific significance and potential application value.

评估说明

    国家自然科学基金项目“新型阳离子环糊精衍生物手性固定相的制备及其在手性药物拆分中的应用研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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