【作者】 谢兴益；

【导师】 冉均国；

【作者基本信息】 四川大学 ， 生物医学工程， 2001， 博士

【摘要】 聚醚聚氨酯材料具有优良的力学性能和生物相容性，在植入装置和人工器官中得到了广泛的应用。但在长期植入体内的过程中存在降解现象，限制了这类材料在长期植入领域的应用。体内炎性反应细胞所释放的酶、自由基、酸性物质等构成了复杂的破坏植入材料的化学体系。目前的研究发现聚碳酸酯聚氨酯具有较好的耐体内氧化性，但仍存在水解的问题。含氟高分子材料，如聚四氟乙烯，具有优良的生物稳定性和生物相容性，但力学性能较差。因此将含氟的化合物引入聚氨酯分子链中，综合两类材料的优点，将可能得到生物稳定性、生物相容性、和力学性能均优良的新型高分子材料。本论文以氟碳化合物封端来提高聚碳酸酯聚氨酯的生物稳定性。研究了脂肪族聚碳酸酯二醇和聚碳酸酯聚氨酯的合成工艺、反应机理及性能；以此为原料合成出一种新型氟碳化合物封端的聚碳酸酯聚氨酯材料，全面研究了其合成工艺、表面和本体结构、以及生物学性能和力学性能。 在合成脂肪族聚碳酸酯二醇的过程中发现有两个因素影响反应原料(碳酸二乙酯和脂肪族二醇)的配比。一是“环状碳酸酯—脱羧”副反应消耗反应原料，其反应机理为：聚碳酸酯齐聚物的端羟基通过与邻近的碳酸酯键发生分子内的酯交换反应生成环状碳酸酯，环状碳酸酯脱羧后生成环醚(如四氢呋喃)。另一个因素是碳酸二乙酯本身随小分子产物乙醇蒸馏出来，约有10％的损失。为了合成出具有设计分子量的聚碳酸酯二醇，在配方设计时必须考虑副反应和蒸馏过程对原料的消耗，因此副反应机理的研究对脂肪族聚碳酸酯二醇的配方设计有指导意义。研究还表明以1，4-丁二醇、1，5-戊二醇、1，6-己二醇为原料的均聚合的聚碳酸酯二醇为结晶性化合物；以1，6-己二醇和1，5-戊二醇的混合二醇(摩尔比3：2)为原料的共聚合的聚碳酸酯二醇(PHPC)为一种无定形的液态低聚物。 制得了具有优良回弹性的聚碳酸酯聚氨酯材料，其软段为共聚的聚碳酸酯 四川大学博士学位论文二醇。以均聚的聚碳酸酯二醇和以共聚的聚碳酸酯二醇为软段的聚氨酯材料都具有软、硬段“微相分离”的结构，两相均为非晶态。两类聚氨酯材料都有优良的拉伸强度N0～60MPa）o 以软段为共聚结构的聚碳酸酯聚氨酯为本体材料，以2，2，3，3，4，4，5，5，6，6，7，7，8，8，8－十五氟－l－辛醇（PDFOL）作封端剂，制备出了具有良好表面特性的新型氟碳化合物封端的聚碳酸酯聚氨酯材料（PCU－1058F），其表面氟含量为本体含量的 90～100倍，材料从表面至本体形成了三层结构：第一层（约0 A～50 A深度）为氟碳端基富集层，第H层（约50 A～100 A）为硬段富集层，第三层（ol00A）为本体材料。我们将这种独特的结构称为“三明治结构”。PCU上 材料保留了聚碳酸酯聚氨酯本身优良的力学性能。 从表面形貌、分子量变化和表面化学结构的变化三个方面研究了材料的体外生物稳定性。采用玻璃棉－HZO。们。体系和磷酸缓冲液oBS，0．IM，pH习．4）分别模拟体内氧化降解和酸水解环境。老化 100天后聚醚聚氨酯出现严重氧化降解裂纹，聚碳酸酯聚氨酯（PCU）以及PCU－1058F在氧化和水解条件下均未出现降解裂纹。PCU－1058F在氧化和水解条件下，数均分子量分别下降了＊％和4％：而同样条件下，肚U分别下降了36％和29％。XP S分析表明＊＊U在氧化条件下材料表面的二－O基团含量提高了一倍（由于氧化人 而PCU刁 表面昼O基团含量基本不变。说明材料表面由于具有特殊的“三明治结构”，大大提高了材料的生物稳定性。本文的研究为生物稳定性聚氨酯的制备开辟了一条新的途径。 所有的聚碳酸酯聚氨酯以及氟碳化合物封端的聚碳酸酯聚氨酯材料均通过了溶血试验。血小板粘附试验和动态凝血时间试验表明PCU－1058F由于氟碳端基的富集提高了材料的血液相容性。更多还原

【Abstract】 Polyurethanes are one of the most important thermoplastic elastomers and have been widely used in medical-device manufacturing as well as in other applications. However, their long-term performances in biological environment are not acceptable to date. Particularly, they are known to degrade in vivo by hostile substances (enzymes, super oxide anion, hydroxyl radical, H2O2 and acids, etc.) released by macrophages and foreign body giant cells during inflammatory response stimulated by the foreign materials. In addition, fluoropolymers, such as polytetrafluoroethylene, have good chemical stability but poor mechanical properties. So, introducing fluorinated chains into the backbones of polyurethanes maybe will produce novel polyurethanes having good mechanical properties, acceptable biocompatibility and long-term biostability. In this dissertation, a fluorinated alcohol, 2,2, 3, 3,4,4, 5, 5,6, 6, 7, 7, 8, 8, 8-pentadecafluoro-l-octanol (PDFOL) was used as an end-capping reagent to polycarborate urethanes during synthesis these polyurethanes through bulk polymerization. And its hemocompatibility and biostability were also investigated in this thesis.As the starting materials for polycarbonate urethanes and fluorocarbon end-capped polycarbonate urethanes, a series of aliphatic polycarbonate diols were synthesized by carbonate interchange reaction of aliphatic diols with diethyl carbonate (DEC). Gas Chromatogram Analysis revealed that there were about 2.54% (by weight) tetrahydrofuran and very lillte (0.154%, by area) tetrahydropyran in the distillations of 1,4-butanediol/DEC and 1,5-pentanediol/DEC reaction systems, respectively. A "cycloalkylene carbonate-decarboxylation" mechanism was proposed for interpretation the formation of the side products. X-ray diffraction and DSC demonstrated that homopolycarbonate diols from 1,4-butanediol, 1,5-pentanediol and 1,6-hexanediol were semicrystalline polymers while copolycarbonate diol from 1,6-hexanediol and 1,5-pentanediols (3:2, mole ratio), PHPC, was an amorphous polymer. It was a pale-yellow liquid at room temperature.Polycarbonate urethanes (PCU) were synthesized from aliphatic polycarbonate diols as soft segments and MDI/BDO as hard segments. IR spectra, DSC analysis and X-ray diffraction revealed that all polycarbonate urethanes had microphase separation structures and the two phases in bulk polymers were amorphous. The degree ofmicrophase separation increased with the increasing of molecular weights of the soft segments. All polycarbonate urethanes had high tensile strength (30-60MPa) and moderate elongation at break (300-450%). Particularly, the polycarbonate urethane from copolycarbonatediol, PHPC, exhibited improved flexibility and elastic recovery as compared to those from homopolycarbonatediols.PDFOL end-capped polycarbonate urethanes (PCU-1058F) were synthesized from PHPC as soft segment and MDI/BDO as hard segment. About 2% w/w PDFOL in the total reactants generated a polymer with nonwettable surface. Bulk elemental analysis and X-ray photoelectron spectrum (XPS) showed that the atom percents of fluorine at outermost surfaces were as much as 90 - 100 times of those in the bulk. Because of the high surface activity of fluorocarbon tails, PCU-1058F formed three different layers from outermost surfaces into the bulk materials, that is, firstly fiuorocarbon-dominated (about 0A-50A), then hard-segments dominated (about 50A-100 A) and finally the bulk-dominated (about >100 A), which were called "Sandwich Structure".The in vitro biostability of polycarbonate urethanes and fluorocarbon-terminated polycarbonate urethanes were test by Zhao’s "Glass wool-H2O2/CoCl2" test system and PBS (0.1M, PH=3.4) test system. After 100 days in both tests, no stress cracks were observed on both materials. GPC analysis demonstrated that fluorocarbon-terminated polyurethane exhibited slower molecular weight decrease than fluorocarbon non-terminated ones. In the case of "Glass wool-H2O2/CoCl2" test, the content of C-O sharply increased as for polycarbonate ureth更多还原