【作者】 陈枫；

【导师】 沈之荃；

【作者基本信息】 浙江大学 ， 高分子化学与物理， 2008， 博士

【摘要】 近年来,生物可降解高分子材料被广泛应用于药物控制释放,手术缝合线,人造皮肤,骨固定和修复以及细胞组织工程等领域。与非生物降解型高分子材料相比,生物降解型具有更大的优点,它不需要二次手术,是生物医用高分子材料发展的主流方向,本文概述了生物可降解高分子材料的研究进展。其中聚酸酐类和脂肪族聚碳酸酯类可降解性高分子材料是80年代初发展起来的一类新型可生物降解材料。由于其具有良好的生物相容性、表面溶蚀降解性、降解速度可调及易加工性等优异性能,很快在医学前沿领域得到应用。本文概述了聚酸酐和脂肪族聚碳酸酯合成进展和临床应用概况。采用低毒性的芳氧基稀土催化剂——二（2,6-二叔丁基-4-甲基苯氧基）稀土[Ln（DBMP）₃]在温和的条件下单组分催化己二酸酐的开环均聚合,并系统研究了溶剂,温度、聚合时间、单体催化剂比例等因素对聚合的影响,发现不同的稀土元素配合物对于催化己二酸酐开环均聚合都具有较高的活性。PAA通过¹H NMR分析分子量为1,500。使用La（DBMP）₃催化己二酸酐与己内酯的嵌段共聚,制备了一系列不同单体比例的嵌段共聚物,共聚物结构通过GPC,′H NMR、DSC等手段表征证实。而相同条件下己二酸酐与2,2-二甲基三亚甲基环碳酸酯和三亚甲基环碳酸酯开环共聚合证明只有PAA和聚碳酸酯的共混物。使用三氟甲磺酸稀土[Ln（OTf）₃]催化己二酸酐和环氧丙烷开环共聚合。详细讨论了不同的稀土催化剂等反应条件对于共聚合的影响。可以通过调节反应条件制备AA和PO的交替共聚物。在[AA]:[PO]=1:1,[AA+PO]/[Y（OTf）₃]=1000,80℃反应48小时,可以制备AA与PO的交替共聚物（M_n=4,600）。使用。¹H NMR分析反应机理,发现反应非常复杂,需要进一步研究。使用Ln（DBMP）₃单组分催化碳酸亚民乙酯和CL开环共聚合,成功制备了一系列具有较高分子量、EC含量不同的Poly（CL-co-EC）s。详细研究了不同稀土元素的Ln（DBMP）₃的催化活性,发现轻稀土La和Nd具有最好的催化活性,Nd（DBMP）₃催化制备的共聚物分子量最高。详细研究了Nd（DBMP）₃催化EC和CL开环共聚合的聚合特征。得出了最佳聚合条件为:单体投料比[EC]:[CL]=30:70,[EC+CL]=1.0 mol/L,[EC+CL]/[Nd（DBMP）₃]=500,T=25℃,甲苯溶液,聚合时间3 h。共聚物的数均分子量15.97万,分子量分布为1.81。使用¹H NMR检测表明没有发生EC单体的均聚合和脱CO₂副反应发生,所得共聚物为无规共聚物,共聚物中的EC含量最高为22 mol-%。使用XRD测定了不同EC含量共聚物的结晶度,结果表明EC的含量越高,共聚物的结晶度越低。使用DMA检测了共聚物的热学和力学性能。结果显示共聚物只有一个玻璃化转变温度（T_g）（-35.6℃）,随着EC含量的增加,T_g有所增加,但是T_m有较大下降（44.5℃）。拉伸测试测定了共聚物在25℃时的强度、杨氏模量和断裂伸长率的变化趋势。从结果中可以得到随着EC含量的增加,共聚物代表刚性的模量和强度指标大幅下降,而代表柔韧性的断裂伸长率大幅增加（2383%）的结论。采用“原位聚合”的方法合成了一系列分子量不同的PAA与PCL-b-PAA、PDTC和PTMC共混物。通过浇铸成膜的技术制备了几种共混物薄膜,并与简单溶液共混制备的相应的共混物薄膜做了在PBS溶液（pH=7.42）体外降解试验。实验表明PAA在24h内已降解完毕,是一种快速降解材料。PAA的降解对剩余的PCL、PDTC和PTMC的降解没有明显影响。通过观察比较“原位聚合”和溶液共混制备的聚合物薄膜的降解前后的形貌,发现“原位聚合”制备的共混聚合物中PAA的分散优于溶液共混制备的材料,体外降解后微孔在薄膜本体和表面分布得更均匀,有望用作生物医用材料如组织工程支架。采用Ln（DBMP）₃可以成功的催化制备可降解聚合物Poly（CL-co-EC）s。使用静电纺丝技术制备了直径为1μm数量级的无纺布。对共聚物材料的生物相容性试验的初步结果显示,共聚物具有良好的细胞粘附性;溶血试验、细胞增值实验和细胞毒性试验表明无明显细胞毒性:同时肌肉植入试验表明共聚物在肌肉组织内不会引起严重的炎症反应,无炎症薄膜的形成。通过细胞培养实验,发现静电纺丝制备的无纺布比光滑平面薄膜更容易粘附生长细胞,可以用作组织工程支架。更多还原

【Abstract】 In recent years, biodegradable polymeric materials have been used for drug delivery, bone and cartilage repairing, tissue engineering. Compared to nonbiodegradable polymers, they have favorable advantages. That is, they do not need to be taken out and can degrade into small molecules in body. Biodegradable polymers are the most potential materials for biomedical applications. In this paper, recent developments of biopolymers were reviewed. Novel biodegradable polymers, polyanhydrides and aliphatic polycarbonate have been developed since 1980s’. These materials are highly biocompatible, demonstrated by tissue response and toxicological study. In addition, they show surface-eroding behavior, thus provide a sustained release rate over a long period of time, and the rate is adjustable. So these materials are very promising in biomedical applications. This paper presented an outline of recent researches and clinical applications of these polymers.Lanthanum tris(2,6-di-tert-butyl-4-methylphenolate) was applied to catalyze the ROP of AA and the copolymerization of AA with CL. Various conditions were examined. The copolymer structures are identified by GPC, ~1H NMR and DSC. Only PAA/PDTC or PAA/ PTMC blends were obtained by the copolymerization of AA and DTC or TMC.The ring-opening copolymerization of adipic anhydride with propylene oxide has been carried out using yttrium triflates as a catalyst. Poly(propylene adipate) could be synthesized by controlling the copolymerization conditions. Poly(AA-alt-PO) with M_n=4,400, could be synthesized. The copolymerization procedure was tracked by ~1H NMR analysis and was found that the mechanism is very complex.The ring-opening copolymerization of ethylene carbonate (EC) with (CL) was carried out using Ln(DBMP)3 as a single component catalyst. Copolymers containing 22.0% EC contents with high molecular weights (up to 23.97×10~4) and moderate molecular weight distributions (between 1.66 and 2.03) were synthesized at room temperature. Compared with homopoly(ε-caprolactone), the copolymers with EC units (22.0%) exhibited higher glass transition temperatures (-35.6℃), lower melting temperatures (44.5℃) and greatly enhanced elongation at break (2383%) based on dynamic mechanic analysis. The crystallinities of the copolymers decreased with the increasing EC molar percentage in the products.PAA/PCL-b-PAA, PAA/PDTC and PAA/PTMC blends were prepared by in situ copolymerization and solution blending methods. The matrices were degraded in vitro. PAA degraded fast within 24 h. Porous membranes were remained. It is founded the membranes of the matrices prepared by in situ polymerization have more regular cavities.Poly(CL-co-EC)s were proved as a suitable and biocompatible copolymer with the changeable physico-mechanical properties. Biocompatibility tests of the copolymers showed that they good cell adhesion, growth viability, morphology and mitochondrial activity of L929 cells. Hemolysis test and muscle transplantation approved poly(CL-co-EC)s could be used as biocompatible material.更多还原