X光显影生物可降解聚氨酯合成及性能评价

发布时间：2018-03-04 12:39

  本文选题：聚氨酯　切入点：X光显影　出处：《大连理工大学》2014年博士论文　论文类型：学位论文

【摘要】：近年来,X光机等医疗影像设备不断发展进步,X光显影材料能够辅助介入微创手术中准确定位并实现非侵入式术后跟踪植入体,因此受到医学界和广大患者的广泛认可。然而,聚氨酯等医用高分子材料自身不具备X光可视化功能,研究如何赋予聚氨酯X光显影功能将有助于拓宽聚氨酯作为人工介入材料的发展应用,具有非常重要的现实意义。本文采用“碘扩链剂”化学合成法,分别选取聚丁二酸丁二醇酯(PBS)、聚己内酯(PCL)和聚乳酸(PLA)三种生物可降解低聚物二醇做软段,四碘代双酚A(IBPA)作为扩链剂和X光显影剂,脂肪族异佛尔酮二异氰酸酯(IPDI)为原料合成一系列含碘聚氨酯,重点探究碘原子引入对聚合物结构与性能的影响规律,并考察含碘聚氨酯在栓塞剂领域的潜在应用。论文的主要内容如下： 1)以PBS为软段合成了三种不同组成的碘代聚丁二酸丁二醇酯基聚氨酯(I-PBSU),并与不含碘聚氨酯对比研究了碘原子引入对聚合产物结构与性能的影响。结果表明引入空间位阻较大的碘原子使得聚氨酯软段PBS的结晶能力和结晶度下降,结晶形态由环带球晶逐渐消失进而变成不规则织构,熔融行为也变得更为复杂。提出了I-PBSU熔融过程中存在一个热力学亚稳态和两次熔融再结晶过程,解释了碘原子引入所导致的复杂多重熔融行为,为关联聚集态结构与性能提供基础。 2)以PCL为软段合成了三种不同组成的碘代聚己内酯基聚氨酯(I-PCLU),并与不含碘聚氨酯做对比研究,详细探讨了碘原子引入对聚合产物的降解行为及其X光衰减规律的影响,并研究I-PCLU/DOX载药微球的药物释放动力学和抑瘤效果。结果表明,空间位阻较大的碘原子是导致I-PCLU降解延迟的原因,酶解过程中碘原子较牢固地键接在聚合产物分子链上,因而X射线辐射不透过性衰减缓慢,表现出良好的显影示踪性。制备了两种碘代聚氨酯载药微球(I-PCLU/DOX),具有均匀的药物负载和药物缓释效应,对Hela肿瘤细胞表现出一定的抑制作用,这为X光显影聚氨酯微球在介入栓塞剂领域的进一步应用提供了理论依据和实验支持。 3)以不同分子量PLLA为软段合成了六种不同组成的碘代聚乳酸基聚氨酯(Ⅰ-PLAU)。结果表明,随软段PLLA分子量增大, I-PLAU结晶能力增强,热稳定性提高；随IBPA含量增大,I-PLAU结晶受到抑制,热稳定性略有下降,X光显影性明显提升。X光显影测试、血液相容性和生物相容性实验结果表明,合成的I-PLAU材料均能在X光下清晰显影,具有一定的促凝血性能、良好的生物相容性和可降解性。I-PLAU/DOX微球具有较好的药物负载能力和药物缓释效应,释药行为符合双相动力学模型,初步证实X光显影生物可降解碘代聚氨酯在介入栓塞剂领域具有潜在的应用前景。
[Abstract]:In recent years, medical imaging equipment, such as X-ray machines, has been developing continuously. X-ray materials can assist in the accurate positioning of interventional minimally invasive surgery and realize the tracking of implants after non-invasive surgery. Therefore, it has been widely recognized by the medical profession and the broad masses of patients. Medical polymeric materials such as polyurethane do not have the function of X-ray visualization, so it will be helpful to broaden the development and application of polyurethane as artificial interventional materials. In this paper, three kinds of biodegradable oligomer diols, poly (butylene succinate), polycaprolactone (PCL) and polyllactic acid (PLA), were selected as soft segments by using "iodine chain extender" chemical synthesis method. A series of iodized polyurethane was synthesized by using tetraiodobisphenol A (IBPA) as chain extender and X-ray contrast agent, aliphatic isophorone diisocyanate (IPDIII) as raw material. The influence of iodine atom on the structure and properties of polymer was studied. The potential applications of iodized polyurethane in the field of embolic agent were also investigated. The main contents of this paper are as follows:. 1) three kinds of iodide polybutylene succinate polyurethane (I-PBSUU) were synthesized with PBS as soft segment. The effect of iodine atom addition on the structure and properties of the polymerization product was compared with that of iodized polyurethane. The iodine atom with larger intersteric resistance decreases the crystallinity and crystallinity of PBS in soft segment of polyurethane. The crystalline morphology gradually disappeared from the ring spherulites to irregular textures, and the melting behavior became more complicated. A thermodynamic metastable process and a two-melting recrystallization process were proposed in the melting process of I-PBSU. The complex multi-melting behavior caused by the introduction of iodine atoms is explained, which provides the basis for the structure and properties of correlated aggregation states. 2) three kinds of iodide polycaprolactone polyurethane (I-PCLUU) with different composition were synthesized with PCL as soft segment, and compared with iodized polyurethane. The effects of iodine atom on the degradation behavior and X-ray attenuation of polymerization products were discussed in detail. The drug release kinetics and tumor inhibition effect of I-PCLU / DOX microspheres were studied. The results showed that iodine atoms with large steric hindrance were responsible for the delayed degradation of I-PCLU, and iodine atoms were firmly bonded to the molecular chain of polymerization products during enzymatic hydrolysis. Two kinds of iodized polyurethane loaded microspheres (I-PCLU / DOXX) have been prepared, which have uniform drug loading and drug release effect, and have a certain inhibitory effect on Hela tumor cells. This provides theoretical basis and experimental support for the further application of X-ray developed polyurethane microspheres in the field of interventional embolization. 3) six kinds of iodide polylactic acid polyurethane (鈪，

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