本文選題：聚氨酯　切入點(diǎn)：X光顯影　出處：《大連理工大學(xué)》2014年博士論文　論文類型：學(xué)位論文

【摘要】：近年來,X光機(jī)等醫(yī)療影像設(shè)備不斷發(fā)展進(jìn)步,X光顯影材料能夠輔助介入微創(chuàng)手術(shù)中準(zhǔn)確定位并實(shí)現(xiàn)非侵入式術(shù)后跟蹤植入體,因此受到醫(yī)學(xué)界和廣大患者的廣泛認(rèn)可。然而,聚氨酯等醫(yī)用高分子材料自身不具備X光可視化功能,研究如何賦予聚氨酯X光顯影功能將有助于拓寬聚氨酯作為人工介入材料的發(fā)展應(yīng)用,具有非常重要的現(xiàn)實(shí)意義。本文采用“碘擴(kuò)鏈劑”化學(xué)合成法,分別選取聚丁二酸丁二醇酯(PBS)、聚己內(nèi)酯(PCL)和聚乳酸(PLA)三種生物可降解低聚物二醇做軟段,四碘代雙酚A(IBPA)作為擴(kuò)鏈劑和X光顯影劑,脂肪族異佛爾酮二異氰酸酯(IPDI)為原料合成一系列含碘聚氨酯,重點(diǎn)探究碘原子引入對聚合物結(jié)構(gòu)與性能的影響規(guī)律,并考察含碘聚氨酯在栓塞劑領(lǐng)域的潛在應(yīng)用。論文的主要內(nèi)容如下： 1)以PBS為軟段合成了三種不同組成的碘代聚丁二酸丁二醇酯基聚氨酯(I-PBSU),并與不含碘聚氨酯對比研究了碘原子引入對聚合產(chǎn)物結(jié)構(gòu)與性能的影響。結(jié)果表明引入空間位阻較大的碘原子使得聚氨酯軟段PBS的結(jié)晶能力和結(jié)晶度下降,結(jié)晶形態(tài)由環(huán)帶球晶逐漸消失進(jìn)而變成不規(guī)則織構(gòu),熔融行為也變得更為復(fù)雜。提出了I-PBSU熔融過程中存在一個熱力學(xué)亞穩(wěn)態(tài)和兩次熔融再結(jié)晶過程,解釋了碘原子引入所導(dǎo)致的復(fù)雜多重熔融行為,為關(guān)聯(lián)聚集態(tài)結(jié)構(gòu)與性能提供基礎(chǔ)。 2)以PCL為軟段合成了三種不同組成的碘代聚己內(nèi)酯基聚氨酯(I-PCLU),并與不含碘聚氨酯做對比研究,詳細(xì)探討了碘原子引入對聚合產(chǎn)物的降解行為及其X光衰減規(guī)律的影響,并研究I-PCLU/DOX載藥微球的藥物釋放動力學(xué)和抑瘤效果。結(jié)果表明,空間位阻較大的碘原子是導(dǎo)致I-PCLU降解延遲的原因,酶解過程中碘原子較牢固地鍵接在聚合產(chǎn)物分子鏈上,因而X射線輻射不透過性衰減緩慢,表現(xiàn)出良好的顯影示蹤性。制備了兩種碘代聚氨酯載藥微球(I-PCLU/DOX),具有均勻的藥物負(fù)載和藥物緩釋效應(yīng),對Hela腫瘤細(xì)胞表現(xiàn)出一定的抑制作用,這為X光顯影聚氨酯微球在介入栓塞劑領(lǐng)域的進(jìn)一步應(yīng)用提供了理論依據(jù)和實(shí)驗(yàn)支持。 3)以不同分子量PLLA為軟段合成了六種不同組成的碘代聚乳酸基聚氨酯(Ⅰ-PLAU)。結(jié)果表明,隨軟段PLLA分子量增大, I-PLAU結(jié)晶能力增強(qiáng),熱穩(wěn)定性提高；隨IBPA含量增大,I-PLAU結(jié)晶受到抑制,熱穩(wěn)定性略有下降,X光顯影性明顯提升。X光顯影測試、血液相容性和生物相容性實(shí)驗(yàn)結(jié)果表明,合成的I-PLAU材料均能在X光下清晰顯影,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微球具有較好的藥物負(fù)載能力和藥物緩釋效應(yīng),釋藥行為符合雙相動力學(xué)模型,初步證實(shí)X光顯影生物可降解碘代聚氨酯在介入栓塞劑領(lǐng)域具有潛在的應(yīng)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，

本文編號：1565694