6-O-羧甲基壳聚糖的硫酸酯化及其产物的抗凝血活性

Preparation and Anticoagulant Activity of the Sulfated 6-O-Carboxymethyl Chitosan

以甲壳素为原料,采用低温羧甲基化反应制备C6位取代羧甲基甲壳素(6-O-CMCH),然后脱去C2位乙酰基得到C6位取代羧甲基壳聚糖(6-O-CMCS),最后将6-O-CMCS与氯磺酸-浓硫酸反应,通过控制反应条件,获得了取代位置和取代度部分可控的硫酸酯化6-O-CMCS。利用电位滴定、元素分析、FT-IR、1 H-NMR测试分析各级产物的化学结构,并测定终产物活化部分的凝血活酶时间(APTT)、血浆凝血酶原时间(PT)及血浆凝血酶时间(TT)。实验结果表明:硫酸酯化6-O-CMCS与高分子量肝素的结构和抗凝血活性类似,其抗凝血活性机理主要体现在对内源性和共同凝血途径的抑制。

6-O-carboxymethyl chitin （6-O-CMCH） was prepared from chitin at low temperature, and then 6-O-CMCH was deacetylated to obtain 6-O-carboxymethyl chitosan （6-O-CMCS）. The sulfated 6-O-CMCS with limited controllable substitution was prepared by a controlled reaction between 6-O-CMCS and chlorosulfonic acid/concentrated sulfuric acid. 6-O-CMCH and sulfated 6-O-CMCS were characterized with conductometric titration, elemental analysis, FT-IR, and 1H-NMR methods. The sulfated 6-O-CMCS was measured to determine its activated partial thromboplastin time （APTT）, prothrombin time （PT） and thrombin time （TT）. Results indicated that the structure and blood anticoagulation of sulfated 6-O-CMCS were similar to that of heparin, and its activity of blood anticoagulation was mainly due to the suppression of endogenous and common coagulation pathway.