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分子印迹及相关技术用于手性药物那格列奈的拆分

Application of Molecular Imprinting and Related Technologies on Chiral Separation of Nateglinide

【作者】 尹俊发

【导师】 杨更亮;

【作者基本信息】 河北大学 , 分析化学, 2004, 硕士

【摘要】 分子印迹技术是一项集高分子聚合物制备、高选择性分子识别、分离富集等手段为一体的综合性技术。本论文应用分子印迹技术,以非磺脲类降血糖手性药物那格列奈为模板分子,分别采用本体聚合法、原位聚合法、沉淀聚合法制备了无定形、连续整体和微球形具有特定识别和手性拆分性能的分子印迹聚合物,用作高效液相色谱手性固定相实现了那格列奈分子与其对映体的手性拆分。全文分为如下五个部分: 第一章:介绍了分子印迹技术的原理、研究应用和进展状况,并概述了高效液相色谱及相关技术在药物分析中的应用。 第二章:采用本体聚合法、原位聚合法、沉淀聚合法制备了不同形态那格列奈分子印迹聚合物,并用作高效液相色谱手性固定相考察其对那格列奈分子与其对映体的拆分色谱行为。 第三章:考察了那格列奈印迹聚合物的吸附特性和手性分离过程中的热力学性质。 第四章:应用那格列奈分子印迹聚合物对那格列奈与其几何异构体进行拆分,并讨论了MIP分子识别机理。同时对分子印迹技术在结构类似物分离方面的应用作了简单介绍。 第五章:应用HPLC—ELSD技术对药物中的胆酸,植物中的水苏糖进行了检测,并预测了这项技术与分子印迹技术相结合在药物分析中的应用前景。 实验通过对那格列奈印迹聚合物合成、手性拆分的色谱行为、吸附特性和热力学性质等内容的考察,验证了那格列奈印迹聚合物作为色谱手性固定相的可行性和应用优势。

【Abstract】 Molecular Imprinting Technology (MIT) has been proved to be an effective tool for chiral separation, solid-phase extraction, sensors, etc. In this thesis, molecularly imprinted polymers (MIP) based on nateglinide, an orally drug of active secretagogue, were prepared and have been used as HPLC chiral stationary phases (CSP). The chromatographic performance, absorption and thermodynamic characteristics of chiral separation on MIP-CSP were investigated. There are five chapters in this thesis.In Chapter I, the principle of MIT, polymerization methods, application of this technique and its future developments were introduced. And the applications of HPLC on chiral separation and HPLC-ELSD technology were also described.In Chapter II, bulk, rod and microsphere MIP were prepared by different approaches. Experiments showed that all of those MIP had wonderful enantio-selectivities on nateglinide and its L-enantiomer even their chromatographic performances were different.In Chapter III, the characteristics of adsorption and thermodynamics of nateglinide-MIP were investigated. The adsorption isotherms of neteglinide and L-enantiomer were studied by static method. Schatchard analysis indicated that two classes of binding site were present in the imprinted polymers.In Chapter IV, separation of neteglinide and its cw-isomer on nateglinide-MIP was performed and the recognition mechanism was deduced. Meanwhile, the analog compound separations on MIP were also introduced.In Chapter V, cholic acid in An-Gong Niuhuang capsules and stachyose in Stachys sieboldii Miq. were determined by HPLC-ELSD. It was expected that the MIP could be used more widely by using this HPLC-ELSD method.

  • 【网络出版投稿人】 河北大学
  • 【网络出版年期】2004年 04期
  • 【分类号】TQ463
  • 【被引频次】2
  • 【下载频次】444
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