【作者】 杨越冬；

【导师】 于九皋；

【作者基本信息】 天津大学 ， 有机化学， 2007， 博士

【摘要】 壳聚糖具有聚阳离子电解质的特性,作为血液接触材料时容易吸附血细胞形成血栓或使血细胞膜变形而发生溶血。本研究将壳聚糖氧化制备成6-羧基壳聚糖,再将-SO3H基团接枝到6-羧基壳聚糖分子上制备磺化6-羧基壳聚糖,并系统研究了6-羧基壳聚糖和磺化6-羧基壳聚糖结构、理化性质和血液相容性。首次观察到在碱性环境中沉淀析出的β-壳聚糖分子具有平行链形成的微纤结构;建立了在冰乙酸介质中,以NO2氧化多孔壳聚糖分子中C6位羟甲基制备6-羧基壳聚糖的方法,一次反应氧化度可达47%,由于冰乙酸介质可部分吸收在反应过程中生成的水,明显降低了氧化降解等副反应。系统研究了6-羧基壳聚糖的理化性质。6-羧基壳聚糖具有两性聚电解质的通性,当6-羧基壳聚糖的脱乙酰度85%、氧化度37%时,其等电点pI=4.9。6-羧基壳聚糖的血液相容性明显高于壳聚糖,6-羧基壳聚糖膜可在不明显降低壳聚糖膜断裂强度的前提下大大提高壳聚糖膜的血液相容性。制备了具有选择性吸附性能的6-羧基壳聚糖均匀颗粒,可有效地吸附尿酸、马尿酸和肌酐,而不吸附牛血清蛋白。制备了与天然抗凝血材料肝素分子结构相似的磺化6-羧基壳聚糖,-SO3H基团以共价键优先联在6-羧基壳聚糖分子中的氨基上、其次是二级羟基、第三是一级羟基。发现了-COOH和-SO3H对抗凝血性能的协同效应,通过控制-COOH和-SO3H的比例得到其抗凝血活性与肝素钠相当的磺化6-羧基壳聚糖钠盐,硫含量为10.5%的磺化6-羧基壳聚糖钠盐的抗凝血活性与肝素钠(含硫10.1%)相当,有望作为价格昂贵的抗凝血材料——肝素的替代物。更多还原

【Abstract】 Chitosan is a nature polysaccharide having similar structure with cellulose. Because of its polycation electrolyte characteristics, chitosan could easily adsorb erythrocytes and thrombocytes, which carried negative charges on the surface, to form thrombus or cause hemolysis when it contacted with blood. In this paper, the microfibers inβ-chitosan sample were observed for the first time. In addition, chitosan was oxidized to 6-carboxychitosan; further more, sulfo groups were grafted on it in formamide medium to give sulfated 6-carboxylchitosan. The structures, properties and blood compatibilities of 6-carboxychitosan and sulfated 6-carboxylchitosan were studied.By dispersing porous chitosan powder in glacial acetic acid, the hydroxymethyl groups of chitosan were successively oxidized to carboxyl groups with NO2 gas to form 6-carboxychitosan. Because glacial acetic acid could soak into porous chitosan powder and absorbed the water produced in the oxidization process, not only the degree of oxidization (DO) of hydroxymethyl groups in 6-carboxychitosan might reach to 47%, much higher than did in other mediums such as tetrachloromethane, water etc, but also the oxidative degradation reaction of chitosan could be weakened obviously. The 6-carboxychitosan has the common characteristics of an amphoteric polyelectrolyte, When the DO and degree of deacetylation of 6-carboxychitosan was 37% and 85%, respectively, the isoelectric point (pI) value of 6-carboxychitosan is 4.9. All antithrombosis test, hemolysis test, and blood cell morphology observation with SEM revealed that 6-carboxychitosan had superior blood compatibility to chitosan. By dipping chitosan films in saturated NO2-glacial acetic acid solution, the hydromethyl groups on the film surface could be oxidized to carboxyl groups without decreasing obviously tensile strength of the films. The blood compatibilities of the modified chitosan films were superior to chitosan ones. By crosslinking 6-carboxy-chitosan with glutaraldehyde, 6-carboxy-chitosan spheres were obtained. 6-Carboxy-chitosan spheres, having no adsorption for albumin, were good adsorbent for some uremic toxins such as uric acid, hippuric acid, etc.6-Carboxychitosan was sulfated with chlorosulfonic acid in formamide to give sulfated 6-carboxylchitosan. In sulfated 6-carboxylchitosan, -SO3H groups were primarily grafted on–NH2, next on secondary–OH, and thirdly on–CH2OH positions. With the content of sulfur in sodium salt of sulfated 6-carboxylchitosan increased, the anticoagulation activity of it increased slowly when the content not more than 4.2%, and rapidly when the content more than 4.2%. When the content of sulfur in sodium salt of sulfated 6-carboxylchitosan was 10.5%, the anticoagulation activity of it was similar with heparin sodium (The content of sulfur was 10.1%). The sodium salt of sulfated 6-carboxylchitosan was more similar with heparin sodium than sodium salt of sulfated chitosan did in both structure and anticoagulation activity.更多还原