结肠靶向偶氮高分子的合成及其体外降解性能

SYNTHESIS AND IN VITRO BIODEGRADATION OF AZO POLYMER FOR COLON-SPECIFIC DRUG DELIVERY

以二环己基碳酰亚胺/N,N-二甲基氨基吡啶为偶联剂,将结肠前体药物5,5′-偶氮二水杨酸(奥沙拉秦)与生物相容的聚乙二醇缩聚,制备得到主链含偶氮键的聚乙二醇-奥沙拉秦(PEO-OLZ)缩聚物.研究表明,改变聚乙二醇链段的分子量,可以方便地调节偶氮缩聚合物的亲水性和生物降解性能.在动物盲肠液中所含的偶氮还原酶的作用下,PEO-OLZ缩聚物的偶氮键发生特异性降解,同时通过酯键的水解,释放出抗结肠炎药物5-氨基水杨酸.该类新型偶氮缩聚物可以作为结肠靶向聚合物前体药,亦可用作结肠定位控释的高分子载体.

By ester coupling reaction with dicyclohexyl carbodiimide/N, N＇-dimethyl amino pyridine as the active carboxyl group reagents, a linear azo polymer was constructed. It combines the unique biocompatibility and hydrophilicity of PEO with the biodegradability and low toxicity of 5,5＇-azodisalicylic acid （Olsalazine, OLZ） used in the management of ulcerative colitis. The resultant condensation polymers were characterized by FTIR, NMR, GPC and DSC methods, it was found that changing the molecular weight of PEO blocks affected the loading ratio of OLZ and resulted in significant differences in the hydration and degradability of the condensation polymers. The therapeutically active mesalamine （5-aminosalicylic acid, 5-ASA） was released from the aqueous PEO-OLZ condensation polymer solution with cecum contents through azo-reduction and hydrolysis. The resultant azo-containing condensation polymer with azo bonds in the main chain can either be used as a polymeric prodrug for 5-ASA or as a colon specific drug delivery carrier for other bioactive substances.