聚酰胺-胺接枝聚膦腈的合成与结构表征

Synthesis and structural performance of polyphosphazene grafted poly (amide amine)

背景:当前大多数研究采用将生长因子或帮助细胞黏附生长的功能蛋白(如细胞黏附蛋白)直接接枝在支架材料表面的方式,这样接枝的功能蛋白质在外界环境下常常显得不稳定,进而容易分解。目的:制备能负载基因并可调节生物相容性及其性能的聚膦腈类组织工程支架材料。设计、时间及地点:单一样本观察,于2007-04/06在北京化工大学化工资源有效利用国家重点实验室完成。材料:六氯环三膦腈为宁波博源化工材料有限公司产品;丙氨酸乙酯盐酸盐为天人生化科技有限公司产品;甲胺盐酸盐为北京石鹰化工厂产品;丙烯酸甲酯为天津市博迪化工有限公司产品。方法:采用两步分子设计方案:第1步先以聚膦腈为主链,制备出一种长链预聚物准备用于组织工程的超支化的支架材料,第2步在前一步的预聚物上接枝附有特定功能的基因片段,通过其原位表达的形式,编码所需的蛋白质和生长因子。首先制备生物相容性好、性能易于调控的丙氨基酸乙酯取代聚膦腈,随后采用分别与乙二胺和丙烯酸甲酯发生取代和加成的方法来制备超支化聚合物。主要观察指标:①丙氨酸乙酯取代聚膦腈(G0.5)的1H-NMR表征。②端氨基聚膦腈(G1.0)的13C-NMR表征。③端酯基聚膦腈(G1.5)的13C-NMR表征。结果:丙氨酸乙酯取代聚合物1H-NMR表征说明丙氨酸乙酯已经成功地接在聚膦腈上,此聚合物为所要得到的G0.5目标产物。超支化端氨基聚膦腈(G1.0)的13C-NMR谱图说明了氨基酯交换反应的发生及G1.0结构的形成。端酯基聚膦腈(G1.5)的13C-NMR表征说明加成反应的发生及G1.5结构的形成。结论:实验设计出用于组织工程的超支化聚膦腈支架材料,并合成了0.5,1.0,1.5代聚酰胺-胺型超支化聚膦腈聚合物,并进行了1H-NMR、13C-NMR结构表征,证实了合成聚酰胺-胺型超支化聚膦腈的可行性。

BACKGROUND： At present, the growth factors or functional protein with adhensive cells are directly grafted to the surface of scaffold in the most of the researches, but always can result in protein decomposition because of instability in external environment. OBJECTIVE： To prepare a proposed polyphosphazene scaffold with regulation of biocompatibility to load containing gene fragments. DESIGN, TIME AND SETTING： An observation of single sample was performed at the State Key Laboratory of Chemical Resource Engineering from April to June 2007. MATERIALS： Hexachlorocyclotriphosphazene was purchased from Ningbo Boyuan Limited Company of Chemical Materials, alanine ethyl ester hydrochloride was purchased from Tianren Limited Company of Biochemical Science, methylamine hydrochloride was purchased from Beijing Shiying Chemical Factory, and methyl acrylate was purchased from Tianjin Bodi Limited Company of Chemical Materials. METHODS： Two-step molecular design was performed： （1） Based on poiyphosphazene chain, preparation of a long-chain prepolymer used for hyperbranched tissue engineering scaffolds; （2） graft gene fragments with certain features to the long-chain prepolymer, through its in situ expression, and code required for protein and growth factor. Firstly, alanine ethyl ester with good biocompatibility, performance and easily controlled was prepared to replace polyphosphazens; subsequently, hyperbranched polymers were prepared by substitution with ethylenediamine and synthesis with methacrylate. MAIN OUTCOME MEASURES： （1） ^1H-NMR performance of alanine ethyl nitrile phosphine substituted poly （G0.5）; （2） ^13C-NMR performance of nitrile phosphine end aminopolysiloxane （GI.0）; （3） ^13C-NMR performance of phosphonic ester side polyethylene nitrile （G1.5）. RESULTS： ^1H-NMR indicated that alanine ethyl ester was successfully grafted on polyphosphazenes, and the polymer was the G0.5 target products. ^13C-NMR of nitrile phosphine end aminopolysiloxane indicated that the exchange of amino ester occurred and G1.0 structure was formed. ^13C-NMR of phosphonic ester side polyethylene nitrile indicated that addition reaction occurred and G1.5 structure was formed. CONCLUSION： Hyperbranched polyphosphazen scaffolds are successfully designed, and 0.5, 1.0, and 1.5 polyphosphazene grafted poly （amide amine） polymers are successfully synthesized. ^1H-NMR and ^13C-NMR performance indicates the feasibility of polyphosphazene grafted poly （amide amine）.