Synthesis，Characterization and Biological Activity of a LMWH Hyperbranched Carboxymethylcellulose Polymer

Abstract:

A strongly negative hyperbranched copolymer （LMWH-grafted CMC，CH） was synthesized by low-molecular-weight heparin （LMWH） grafted onto carboxymethylcellulose （CMC） backbone to improve the biological activities of LMWH via multivalent effect. LMWH with an aldehyde group at their reduce ends （LMWH-CHO） was prepared from heparin degradation by nitrous acid. The amide bond was formed between the amino group of EDA and the carboxylic groups of CMC when catalyzed by EDC and the primary amino groups were introduced to the backbone （CMC-NH2）. LMWH-CHO was thus grafted onto CMC-NH2 by the Schiff-base reaction. The synthesized hyperbranched polymer was characterized by FTIR，NMR and GPC-MALLS to detect its chemical structure and molecular weight. Furthermore，the anticoagulation activities of the polymer were determined. The results showed that the grafted ratio of CMC was 23.7% with a molar ratio of CMC-NH2 to LMWH-CHO of 1∶5. The APTT and PT of the polymer were 146 s and 27.9 s，respectively，which were 1.25-fold and 2-fold higher compared with that of LMWH. In addition，the IC50 value of anti-factor Xa and anti-factor IIa of the polymer were 104.2 nmol/L and 642 nmol/L，respectively. The values were much lower than those of LMWH. In conclusion，LMWH grafted CMC polymer possessed a better anticoagulation activity than LMWH.