【摘要】：聚丙乙交酯(PLGA)是一種重要的生物醫(yī)用材料，它具有良好的生物兼容性和降解周期可控等優(yōu)點(diǎn)。但較弱的親水性能和細(xì)胞粘附力，缺乏豐富的活性基團(tuán)等限制了它在醫(yī)學(xué)領(lǐng)域的應(yīng)用。采用高分子共聚、接枝的方式對(duì)PLGA進(jìn)行改性，改善它的親水性和細(xì)胞親和性、緩解降解過(guò)程中酸性物質(zhì)的積累以及為材料的進(jìn)一步仿生改性提供基礎(chǔ)等，可以進(jìn)一步拓展PLGA在生物醫(yī)學(xué)領(lǐng)域上的應(yīng)用。 本論文采用減壓法，以辛酸亞錫(Sn(Oct)2)為催化劑，制備出了D,L-丙交酯和乙交酯單體。研究了不同提純方法對(duì)兩種單體純度及產(chǎn)率的影響，，結(jié)果表明采用水洗-重結(jié)晶法對(duì)D,L-丙交酯進(jìn)行提純，六次重結(jié)晶后產(chǎn)物純度可達(dá)99.47%。分別以異丙醇和乙酸乙酯作溶劑純化乙交酯，得到產(chǎn)物的產(chǎn)率和純度都偏低；采用異丙醇和乙酸乙酯配合使用的綜合法能得到純度達(dá)92.63%的乙交酯單體。 以D,L-丙交酯、乙交酯和馬來(lái)酸酐為原料，采用開(kāi)環(huán)聚合的方法制備了馬來(lái)酸酐改性的聚丙乙交酯(MPLGA)，通過(guò)FT-IR和1HNMR分析證明馬來(lái)酸酐已成功接入高分子骨架中。研究了催化劑用量、反應(yīng)時(shí)間和反應(yīng)溫度對(duì)MPLGA分子量及分子量分布的影響。結(jié)果表明在催化劑用量為0.03%，反應(yīng)溫度140℃，反應(yīng)時(shí)間36h時(shí)聚合得到的MPLGA重均分子量為5.3×104，分子量分布系數(shù)為1.51。利用MPLGA中酸酐鍵的N-酰化反應(yīng)，制備了乙二胺改性的MPLGA產(chǎn)物EMPLGA，以進(jìn)一步提高聚合物的親水性和生物相容性。最后考察了聚合物改性前后的親水性能的變化，研究發(fā)現(xiàn)EMPLGA的接觸角遠(yuǎn)低于PLGA和MPLGA，說(shuō)明EMPLGA有著優(yōu)異的親水性能，而酸酐鍵的引入使MPLGA的親水性略弱于PLGA。 采用常溫模壓/粒子溶出法，制備了一系列多孔支架材料�？疾炝酥驴讋┝健⒅驴讋┖繉�(duì)支架材料的孔徑、孔隙率、形貌及力學(xué)性能的影響。結(jié)果表明支架的孔隙率與致孔劑用量呈現(xiàn)出正比增長(zhǎng)的關(guān)系；當(dāng)致孔劑用量在90wt%時(shí)，支架的孔隙率可達(dá)81.86%，但支架的力學(xué)性能隨致孔劑增加而呈下降趨勢(shì)。支架的孔徑隨著致孔劑粒徑增大而增大，因此可以通過(guò)控制致孔劑粒子的尺寸和質(zhì)量百分比來(lái)控制多孔支架的孔結(jié)構(gòu)。 研究了MPLGA和EMPLGA支架材料在PBS緩沖溶液中的降解行為。研究發(fā)現(xiàn)隨著降解的進(jìn)行兩種材料的失重率、吸水率都在逐漸增大，而PBS溶液的pH值、支架的力學(xué)性能和分子量都呈下降趨勢(shì)。其中MPLGA支架的失重率增加較快，EMPLGA中氨基的引入緩解了支架在降解過(guò)程中酸積累的問(wèn)題，使材料降解環(huán)境保持在一個(gè)接近中性的狀態(tài)，材料的失重率、力學(xué)性能都呈平穩(wěn)下降趨勢(shì)；而且EMPLGA中大量的親水基團(tuán)使材料的吸水率始終高于MPLGA。多孔支架的孔結(jié)構(gòu)形態(tài)在降解5天后無(wú)明顯變化；10天后在一些孔壁上腐蝕出少量的小孔；在25天時(shí)，已出現(xiàn)了一些較大的孔洞，且支架開(kāi)始出現(xiàn)萎縮塌陷。
[Abstract]:Poly (glycolide) (PLGA) is an important biomedical material with good biocompatibility and controllable degradation cycle. However, its application in medical field is limited by its weak hydrophilicity, cell adhesion and lack of abundant active groups. PLGA was modified by polymeric copolymerization and grafting to improve its hydrophilicity and cellular affinity, to alleviate the accumulation of acidic substances in the degradation process and to provide the basis for further bionic modification of the materials. It can further expand the application of PLGA in biomedical field. In this paper, (Sn (Oct) _ 2 and L-lactide monomers were prepared by decompression method and stannous octanoate (Sn (Oct) _ 2) catalyst. The effects of different purification methods on the purity and yield of two monomers were studied. The results showed that the purity of DL- lactide was 99.47% after six recrystallization by water washing and recrystallization. Using isopropanol and ethyl acetate as solvent to purify glycolide, the yield and purity of the product were low, and the purity of glycolide monomer was 92.63% by using isopropanol and ethyl acetate. Poly (lactide) modified by maleic anhydride (MPLGA),) was prepared by ring-opening polymerization with DL- lactide, glycolide and maleic anhydride as raw materials. FT-IR and 1HNMR analysis showed that maleic anhydride had been successfully inserted into the polymer skeleton. The effects of the amount of catalyst, reaction time and reaction temperature on the molecular weight and molecular weight distribution of MPLGA were studied. The results show that when the amount of catalyst is 0.03, the reaction temperature is 140 鈩

本文編號(hào)：2352545