Water-soluble Polysaccharides And Insoluble Drugs In Click Chemistry

Click chemistry due to its materials easy to get, the reaction efficiency, mild conditions, high yield, easy purification of the product advantages, is more and more widely applicated. Cu (Ⅰ)-catalyzed alkyne and azide groups of compounds of 1,3- dipolar cycloaddition reaction is the most important type of reactions in Click chemistry.Polysaccharide having wide variety of sources, can be successfully in the body environment degraded, while there is no burden on the organ in the body. Polysaccharide are a green harmless medicinal materials. Such as Dextran (Dex).The solubility of the drugs is an important reason for the bad clinical application of many drugs. The drugs have bad performances because of their poor water solubility which makes their application has been seriously affected. To improve the water solubility of insoluble drugs is crucial. Such as paclitaxel (PTX).In this thesis, Self-made water-soluble modified starch and paclitaxel are as the research object, using Click chemistry as a research method. The main works are as follow:1. Water-soluble modified starch is modified by azide. Bromoacetic acid as a spacer, azide groups will be connected to the molecular structure of Water-soluble modified starch. The structures of products by the IR spectrum are identified, confirmed that azide is connected to the Water-soluble modified starch molecules.2. Paclitaxel is modified by terminal alkynyl. By the esterification of Taxol 2'-OH with propargyl acid, the terminal alkyne is connected to the molecular structure of paclitaxel. By IR spectra, UV spectra, NMR structures of products are identified, confirmed that the terminal alkyne is connected to molecules of paclitaxel.3. Water-soluble modified starch modified by the azide and paclitaxel modified by alkynyl occur 1,3-dipolar cycloaddition reaction reacting a five-triazole ring by Cu (Ⅰ) catalysis. Water-soluble modified starch and paclitaxel by Triazole ring are connecting. Getting paclitaxel prodrug of Water-soluble modified starch (WMS-PTX). By IR spectra, UV spectra, the structure of the WMS-PTX is identified.4. Drug loading and water-soluble of the polymeric prodrug is studied. According to H'-NMR data obtained using the formula MS= (I7.2～8.0/16)/ (I4.4-5.7/3), derived polymer precursors, drug loading of about 2% at least. Determined by a graded water prepared water-soluble paclitaxel prodrug polymers, the results show that the solubility of the prodrug is more than 100 mg/ml at 26℃. Solubility of Paclitaxel in water increased at least 8000 times. solubilization effect is obvious.