多糖大分子受连接位点、糖环结构、异头构型和分支等因素的影响，糖链结构呈现复杂性和多样性，虽然契合复杂疾病治疗的标准需求，但其高选择性分离分析一直是糖类药物研发亟需解决的关键科学问题之一。因此，发展多糖高效分离分析新材料、新方法是现代药物分析的重大需求。本项目利用亲水作用色谱填料与糖链之间的亲水作用分离糖类的优势，结合共价有机框架材料的分子排阻效应，将三醛基间苯三酚键合在硅胶表面，引入不同亲水能力和分子尺寸的有机单体，设计并制备具有优越亲水性能、不同孔径的新型核壳共价有机框架纳米孔微球(COFs@SiO2)新型色谱填料，并以低分子肝素(LMWHs)为分离对象，构建多糖分离分析新方法。在此基础上，研究新型色谱填料对LMWHs的保留行为和分离性能的影响；阐明新型色谱填料亲水能力、分子排阻效应对LMWHs分离分析的多模式机制和规律；为发展多糖分离分析新填料、新方法提供技术支撑和理论指导。

The structure of polysaccharide macromolecules presents complexity and diversity due to factors such as the attachment site, the sugar ring structure, the anomeric configuration and the branch. Although it meets the standard requirements for the treatment of complex diseases, its high selective separation and analysis has been one of the key scientific issues that need to be solved in the development of carbohydrate drugs. Therefore, the development of new materials and methods for the efficient separation and analysis of polysaccharides is a major demand for modern drug analysis. This project takes advantage of the hydrophilic interaction between hydrophilic interaction chromatography and sugar chains to separate polysaccharides, and combines with covalent organic framework materials. 2,4,6-Trihydroxy-1,3,5-benzenetricarboxaldehyde is bonded to the surface of the silica gel and has a Schiff base reaction with organic monomers of different hydrophilic capacities and molecular sizes to design and prepare a series of novel core-shell covalent organic framework nanoporous microspheres (COFs@SiO2), which has excellent hydrophilic properties and different pore sizes. Then, a low molecular weight heparin (LMWH) was used as the separation object to construct a new method for polysaccharide separation and analysis. On this basis, the effects of new chromatographic packings materials on the retention behavior and separation performance of LMWHs were investigated. The multimodal mechanism and law of the separation and analysis of LMWHs by the hydrophilicity, molecular exclusion and hydrogen bonding of new chromatographic packing materials are elucidated. This project will provide technical support and theoretical guidance for the development of new fillers and new methods for the separation and analysis of polysaccharides.