中文摘要
真菌多糖具有提高人体免疫力、抗肿瘤和降血糖等多种药理活性,是天然药物研究的热点之一。在多糖的定量分析研究中,传统的同位素标记和荧光标记法难以区分多糖原型和代谢产物,难以排除衍生化试剂对多糖活性的影响,导致多糖的药代动力学研究十分困难,制约了多糖类药物的发展。因此,多糖的药学研究亟需建立准确可靠的定量分析方法。本课题拟采用多种液相分离手段和质谱的In-Source CID及DIA技术,以不同聚合度真菌多糖为研究对象,开展多糖LC-HR-MS/MS定量分析研究。利用建立的方法,进行不同聚合度真菌多糖的药代动力学研究,从而阐明真菌多糖在体内的生物分布、代谢和排泄规律,揭示真菌多糖聚合度大小对其药代特征的影响。本项目的研究对解决多糖药代动力学研究的瓶颈问题提供了方法和技术支持,对多糖类药物的开发及安全性和有效性评价具有重要意义。
英文摘要
Fungal polysaccharides have many pharmacological activities, including immunostimulation, anti-tumor and hypoglycemic activities, which are one of the hot spots of natural medicine research. In the quantitative analysis of polysaccharides, the isotope labeling and fluorescent labeling methods have some disadvantages. These methods cannot distinguish the polysaccharides with their metabolites and the derivative reagents may affect the activities and pharmacokinetics of polysaccharides. The lack of reliable quantitative method has restricted the development of polysaccharides. Therefore, it is necessary to establish an accurate and reliable quantitative method for polysaccharide pharmacy research. In this research, a new LC-HR-MS/MS method has been developed for the determination of fungal polysaccharides with different degrees of polymerization. This LC-HR-MS/MS method is based on several liquid chromatography methods, and In-Source CID or DIA techniques of high resolution mass spectrometer. The method will be applied to a pharmacokinetic study of fungal polysaccharides, the bio-distribution, metabolism and excretion will be clarified and a pharmacokinetic prediction model will be established. This research will provide the method and technical support for solving the bottleneck problem of the pharmacokinetic study of fungal polysaccharides, which has great significance to the development and the safety and effectiveness evaluation of fungal polysaccharides.
