三分枝六聚乙二醇接枝十二胺共聚物的合成及其性能研究

Synthesis of branched polyethylene glycol-co-dodecylamine and its properties

目的合成以三分枝六聚乙二醇为亲水部分、以十二胺为疏水部分的新型两亲性分子三分枝六聚乙二醇接枝十二胺共聚物(PGDA),并对其理化性质进行考察。方法通过苯磺酰化、取代反应、还原反应、酯化后形成酰胺5步反应合成了PGDA。使用核磁和质谱确定其结构和相对分子质量;芘荧光探针法测量其临界胶束浓度;并考察PGDA在水溶液中的形态、37℃稳定性。结果两亲性分子PGDA被成功合成。质谱实测相对分子质量与理论相对分子质量1 171.69吻合;该两亲性分子在水中很容易自组装成胶束,临界胶束浓度为75 mg/L;PGDA胶束37℃孵育24 h粒径无明显变化、稳定性良好。结论成功合成了三分枝六聚乙二醇为亲水部分和以十二胺为疏水部分的两亲性分子PGDA,其在水溶液中具有优良的胶束化行为,有望能作为一种药用辅料在难溶性药物的胶束等制剂中得到应用。

Objective To synthesize a novel amphiphilic molecule branched polyethylene glycol-co-dodecylamine（PGDA） with branched hexa polyethylene glycol being as the hydrophilic segment while dodecylamine as the hydrophobic segment, and study its physicochmical property. Methods PGDA was successfully synthesized through acylation, substitution reaction, reduction reaction and esterification. The chemical structure was verified by NMR and MS analysis. The critical micelle concentrations（CMC） of PGDA were determined by pyrene fluorescence probe spectrometry. The morphology of PGDA in water was examined by transmission electron microscopy and the size of PGDA micelles at 37 ℃ was monitored to assess the stability. Results The amphiphilic molecule was successful synthesized. MS proved the molecular weight of the obtained PGDA was in accordance with the theoretical molecular weight of 1 171.69. PGDA could easily self-assembly into micelles in aqueous solution with critical micelle concentrations of 75 mg/L. The resultant micelles were quite stable after incubation at 37 ℃ with constant particle size. Conclusion The novel amphiphilic molecule PGDA is successfully synthesized, and its ability to easily self-assembly in aquesous solution which suggested that the resultant amphiphilic PGDA may be used as a pharmaceutical adjuvant, especially in micelles preparation for insoluble drugs.