Study On The Synthesis Of Heparinoid Derivatives Of Chitosan And The Determination Of Their Antothrombogenicities

Chitin/(chitosan), next to cellulose, is the second most plentiful biomass(derivatives). Since chitin and chitosan are nontoxic, biodegradable, easy to be film, so they have been applied in treatment of wastewater; agriculture, food and cosmetic. It's biocompatibility and widespread biological activities, in recent years, they have been the hotspot in medical and sanitary field and the extensive applications of chitosan in medical and health care field.The research of hepairnoid derivatives of chitosan is the most interesting field of their chemical modification. The derivatives' preparation, structure and the function involve a lot of fields, such as polymer chemistry, analytical chemistry, molecular biology and pharmacology etc., so it is one of the basic research of cross discipline. At the same time, it is closely related with application technology, such as biochemical industry, chemical technology, clinical medicine, etc.. The research is significant to us in practical application and in theory.In this dissertation, the performance characteristics of chitin/chitosan was surveyed. The trend and the field of its development were analyzed. The enormous potentiality to be exploited and the problem that every profession should be faced were pointed out. The role of chitin/chitosan and their derivatives in medicine was summarized. As the break-through, the heparinoid derivatives of chitosan(esteridicated by sulphuric acid or chlorosulfonic acid) is emphases in this dissertation. We have reviewed its research history and current situation, pointed out the shortcoming of sulfonated esterification of chtiosan. According to these, The influence of concentration of sulfate reagent, temperature and time of the reaction on the S-contents was studied. And we have analyzed the relationship between the structure and performance of derivatives emphatically.In this dissertation, the reaction conditions of deacetylation and the oxidative degradation with H2O2 of chitin/chitosan have been studied. On this basis, the structure parameter of the goal(heparinoid derivatives of chitosan) depends on the parameter of reactant and the condition of reaction. The structures of the derivatives confirmed by IR, 1HNMR and 13CNMR spectrum. The conclusion that the different structure with the different response system. The method to measure the S-content of derivatives was established. Study and point out the chitosan's heparinoid derivatives have anticoagulant activity and antithrombogenicity. the function by measuring the anticoagulation of heparinoid has been evaluated.The dissertation systematically studies the synthesis of sulfated chitosan and the characterization of the derivatives' structure and fix the optimum reactive condition of sulfated chitosan based on the preparation different characterization of chitosan. Divided into three parts, the main task of this dissertation first is the different molecular weight and degree of deacetylation of chitosan is prepared. In the second part of dissertation, different experiment method and reagent is used in the synthesis of heparinoid derivatives of chitosan, at the same time, the structures of the derivatives are confirmed by IR, 1HNMR and 13CNMR spectrum. The third part is that the chitosan heparinoid derivatives' anticoagulant activities are studied and we pointed out that the derivatives have antithrombogenicity.The primary achievement of the disseration are:1. Deacetylation condition of chitosan have been studied. High N-deacetylation chitosan is obtained by the heterogeneous hydrolysis of partially N-deacetylated chitosan with 40-50% aqueous NaOH at 50~70 C in 24h. The influence of temperature, concentration of NaOH and other factors on deacetylation of chitin has also been researched. The low DD chitosan is obtained via the reaction with acetic anhydride. The DD of chitosan/chitin is controlled with different ratio of chitosan and acetic anhydride.2.The oxidative degradation of chitosan in the neutral condition isinvestigated and the effects of concentration of H2O2, temperature and...