本文選題：聚乳酸　切入點：聚三亞甲基碳酸酯　出處：《復(fù)旦大學(xué)》2014年博士論文　論文類型：學(xué)位論文

【摘要】：本論文合成了高分子量的PLLA-TMC-GA三元共聚物,并以對應(yīng)的PLLA-TMC二元共聚物及PLLA和PTMC均聚物作為參比樣,研究了熱性能、力學(xué)性能、酶、水降解行為及生物相容性等基本應(yīng)用性能；采用微雕刻法,設(shè)計并制作了PLLA-TMC-GA三元共聚物血管支架樣品。主要研究內(nèi)容如下：(1)以辛酸亞錫為催化劑,開環(huán)聚合合成了不同序列結(jié)構(gòu)的PLLA-TMC-GA三元共聚物及對應(yīng)的PLLA-TMC二元共聚物和PLLA、PTMC均聚物。研究了PLLA-TMC-GA三元共聚物的分子鏈結(jié)構(gòu)。采用1H NMR和13C NMR對PLLA-TMC-GA三元共聚物的分子鏈序列結(jié)構(gòu)進行了表征,并計算了平均序列長度和序列分布。結(jié)果表明,TMC或GA單元的加入,使得LLA平均序列長度降低；且GA單元替換等量的TMC單元后,LLA平均序列長度更短。分析發(fā)現(xiàn),LLA平均序列長度與TMC或GA含量之間均存在指數(shù)相關(guān)性。(2)詳細研究了PLLA-TMC-GA三元共聚物分子鏈微結(jié)構(gòu)與性能之間的關(guān)系。實驗發(fā)現(xiàn),單體組成對PLLA-TMC-GA三元共聚物熱性能和力學(xué)性能有明顯的影響。TMC和GA單元的引入破壞了PLLA鏈段的規(guī)整度,使得PLLA-TMC-GA三元共聚物的結(jié)晶能力大幅降低。共聚物的結(jié)晶能力由LLA平均序列長度lLLe值決定。在材料的力學(xué)性能方面,GA組分的加入,使得PLLA-TMC-GA三元共聚物的韌性較之PLLA和PLLA-TMC二元共聚物顯著提高,而拉伸強度僅有輕微下降。該結(jié)果對通過單體配比進行共聚物鏈結(jié)構(gòu)的調(diào)控,進而對材料的性能進行控制有很大的參考價值。(3)研究了PLLA-TMC-GA三元共聚物在蛋白酶K水溶液中的降解行為。實驗揭示了PLLA-TMC-GA三元共聚物的酶降解速率是由LLA平均序列長度和結(jié)晶度共同決定的。較短的LLA平均序列長度導(dǎo)致共聚物的結(jié)晶度較低,從而對加快降解速率有利。但是,當(dāng)LLA平均序列長度小于4.0時,共聚物的降解反而會受到抑制。降解過程中,聚合物的LLA含量幾乎不發(fā)生變化,分子量有一定程度的下降。表明在蛋白酶K降解過程中,亦同時存在水解過程。在水分子的增塑和分子量下降的雙重作用下,降解材料的結(jié)晶能力提高,樣品的Tm和△Hm值略有上升。SEM觀察發(fā)現(xiàn)材料主要以表面溶蝕方式降解。(4)研究了PLLA-TMC-GA三元共聚物在PBS緩沖溶液中的降解行為。與PLLA-TMC二元共聚物和PLLA均聚物相比,PLLA-TMC-GA三元共聚物的降解速率更快。樣品的結(jié)晶能力在水分子的增塑和分子量下降等原因下,初始階段出現(xiàn)結(jié)晶度上升；但當(dāng)分子量下降到10,000時,過短的鏈段,使得降解產(chǎn)物結(jié)晶困難。進一步研究發(fā)現(xiàn),PLLA-TMC-GA三元共聚物的水解過程主要分為三個階段：首先是處于無定形區(qū)的GA組分快速降解；隨后,無定形和結(jié)晶不完善區(qū)域LLA的降解開始成為主要因素；最后,降解進一步加劇,晶區(qū)開始瓦解,晶區(qū)中的LLA和裸露出來的GA單元得以繼續(xù)降解。(5)從細胞相容性、血液相容性及免疫相容性角度出發(fā),對PLLA-TMC-GA三元共聚物的生物相容性進行了評價。結(jié)果顯示,PLLA-TMC-GA三元共聚物的細胞毒性小,溶血率較低,具有較好的抗凝血性質(zhì),且刺激細胞釋放細胞因子的濃度較低,表現(xiàn)出良好的生物相容性。(6)采用完全生物可吸收的PLGA纖維增強了PLLA-TMC-GA三元共聚物。結(jié)果表明,氧氣等離子體處理過的PLGA纖維使得PLLA-TMC-GA三元共聚物的力學(xué)強度得到了進一步提升。PLGA纖維不能在蛋白酶K的作用下降解,因此酶解時,PLGA纖維增強復(fù)合材料的失重速率低于PLLA-TMC-GA三元共聚物基體。但由于PLGA纖維具有較快的水解速率,其產(chǎn)生的酸性降解產(chǎn)物催化加速了基體聚合物的降解,使得酶解或水解時基體聚合物的分子量下降速度更快。(7)選取PLLA-TMC-GA三元共聚物為原料,先通過單螺桿擠出機擠出成型具有一定外徑和壁厚的管材。然后,采用微雕刻法,成功制作出血管支架樣品。該支架有望在為血管提供6-9個月的徑向支撐作用后,1-2年內(nèi)完全降解并被人體吸收,避免傳統(tǒng)金屬藥物洗脫支架對血管的長期刺激、以及由此引發(fā)的血管晚期炎癥和再狹窄等問題。因此,本論文開發(fā)的PLLA-TMC-GA三元共聚物具有較高的強度與韌性、合適的降解速率、良好的生物相容性及成型加工性,在血管支架等生物醫(yī)用材料領(lǐng)域具有良好的應(yīng)用前景。
[Abstract]:The molecular weight of three PLLA-TMC-GA copolymer were synthesized in this paper, and the corresponding PLLA-TMC to two yuan PLLA and PTMC copolymer and homopolymer as a reference sample, studied the thermal properties, mechanical properties, enzyme, compatibility and other basic application performance degradation in water and biological behavior; using micro engraving method, design and production of PLLA-TMC-GA three copolymer stent samples. The main contents are as follows: (1) using stannous octoate as catalyst, ring opening of different sequence structure of three PLLA-TMC-GA polymer and the corresponding PLLA-TMC and PLLA two copolymer was synthesized, PTMC homopolymer. The molecular chain structure of PLLA-TMC-GA three. The copolymer molecular chain 1H NMR and 13C NMR sequence structure of PLLA-TMC-GA three copolymer were characterized. The average sequence length and sequence distribution were calculated. The results show that the addition of TMC or GA unit, the LLA average sequence length The degree of reduction; and the GA unit to replace the TMC unit with LLA, the average sequence length shorter. Analysis shows that there were correlation between LLA index and the average sequence length of TMC or GA content. (2) a detailed study of the relationship between three yuan PLLA-TMC-GA copolymer chain microstructure and properties. It was found that the monomer composition the obvious influence of introducing.TMC and GA units to destroy the PLLA segment of three PLLA-TMC-GA polymer tacticity of thermal and mechanical properties, the crystallization ability of PLLA-TMC-GA three copolymer is significantly reduced. The crystallization ability of copolymer LLA value determined by the average sequence length of lLLe. The mechanical properties of materials, component GA added that makes the PLLA-TMC-GA three copolymer toughness compared to PLLA and PLLA-TMC two copolymer significantly increased, while the tensile strength decreased slightly. The only results of the monomer ratio of copolymer chain structure The regulation of material performance control has great reference value. (3) the degradation behaviors of PLLA-TMC-GA copolymer in three proteinase K in aqueous solution. The experiment reveals the enzymatic degradation rate of PLLA-TMC-GA three yuan of copolymer is determined by LLA average sequence length and crystallinity. The average length of sequence is LLA short lead to copolymers of low crystallinity, so as to accelerate the degradation rate advantage. However, when the LLA average sequence length is less than 4, the degradation of the copolymers may be inhibited. The degradation process, the content of LLA polymer almost did not change, the molecular weight decreased to some extent. Show that in the degradation process of K protease at the same time, also exist the hydrolysis process. The dual role of decrease in water molecules plasticization and molecular weight, improve the crystallization ability of degradable materials, samples of Tm and delta Hm value increased slightly the.SEM observation material The main material to surface erosion degradation. (4) the degradation behaviors of PLLA-TMC-GA three copolymer in PBS buffer solution. Compared with PLLA-TMC and PLLA two copolymer homopolymer, copolymer of PLLA-TMC-GA degradation rate three yuan faster. Reason of crystallization capacity of the samples in plastic and molecular weight decreased under water molecules the initial stage, the crystallinity increased; but when the molecular weight decreased to 10000 when the chain is too short, the degradation products of crystallization difficult. Further studies showed that the hydrolysis process of PLLA-TMC-GA three copolymer is mainly divided into three stages: the first is the GA group in the amorphous region of rapid degradation; subsequently, amorphous and the crystallization degradation area of LLA became the main factors; finally, the degradation further intensified, crystal area began to collapse, the GA unit in the crystal region of LLA and exposed to degradation. (5) from the Bao Xiangrong fine Sex, blood compatibility and immunocompatibility perspective on PLLA-TMC-GA three copolymer biocompatibility was evaluated. The results showed that the cytotoxicity of PLLA-TMC-GA three copolymer of small, low hemolytic rate, has good anticoagulant properties, concentration and release of cytokine stimulated cells showed low compatibility good. (6) the bioabsorbable PLGA fiber reinforced PLLA-TMC-GA three copolymer. The results show that the oxygen plasma treated PLGA fiber makes the mechanical strength of PLLA-TMC-GA three copolymer has been further enhance.PLGA fibers do not degrade in the protease K under the action of the enzyme therefore, fiber reinforced PLGA the composite weight loss rate is lower than PLLA-TMC-GA three yuan. But due to the PLGA copolymer matrix fiber has a faster hydrolysis rate, its acidic degradation products with catalytic velocity matrix The degradation of polymers, the enzyme hydrolysis solution or polymer matrix decreased faster. (7) a total of three PLLA-TMC-GA copolymer as raw material, through extrusion molding with a certain diameter and wall thickness of the pipe single screw extruder. Then, using Python Cephas, successfully developed vascular stent the stent is expected to sample. In the 6-9 months to provide radial supporting role for vascular after 1-2 years completely degraded and absorbed by the body, to avoid the traditional metal drug-eluting stent long-term stimulation on blood vessels, and blood vessels caused by late inflammation and restenosis. Therefore, this thesis develops the strength and toughness of PLLA-TMC-GA copolymer with high of three yuan right, the degradation rate, biocompatibility and processability good biological, and has good application prospect in the field of vascular stents and other biomedical materials.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R318.08

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本文編號：1604600