【作者】 余兆菊；

【导师】 刘立建；

【作者基本信息】 武汉大学 ， 高分子化学与物理， 2004， 博士

【摘要】 聚(ε-己内酯)作为一种合成的脂肪族聚酯，由于其良好的生物可降解性、生物相容性以及药物透过性，在生物医学领域得到了广泛研究。本论文综述了聚(ε-己内酯)的研究进展，包括其催化或引发体系、功能化以及微波合成的研究。 为了提高聚(ε-己内酯)的体内生物相容性和生物安全性，拓展ε-己内酯开环聚合的非金属催化或引发体系成为国际上的研究热点。本论文研究了有机羧酸、醇引发的ε-己内酯微波辅助开环聚合。 研究了苯甲酸引发的ε-己内酯微波辅助开环聚合。所得产物经表征为聚(ε-己内酯)且引发剂残基进入到聚合物主链上。反应混合体系于微波功率680W下辐照240分钟，所得聚合物的分子量达到44800g／mol且分散度为1.6。微波功率、辐照时间和引发剂浓度对产物分子量有一定影响。微波功率越高或引发剂浓度越高，反应初期分子量越高但所能达到的最大分子量越低，辐照时间延长有利于提高分子量。微波热效应对聚合反应有明显影响，聚合物链在160至230℃之间迅速增长，并且温度越高链增长越快，当超过230℃时，链增长受到抑制且产物降解现象开始发生。微波辐照下制备的聚合物分子量显著高于常规加热方法制备的聚合物分子量，原因为微波辐照限制了聚合初期链增长中心的形成，单体的消耗主要用于聚合物链长的增长；而不同于加热聚合反应初期，单体的消耗主要用于形成链增长中心。因此，微波促进了聚合物的链增长。 选取三种不同pKa值的氯代乙酸，即一氯乙酸、二氯乙酸和三氯乙酸，研究了引发剂酸性对ε-己内酯微波开环聚合反应的影响。聚合反应除受微波功率、辐照时间和引发剂浓度影响外，还明显受到了引发剂pKa值的影响。引发剂pKa值越低，聚合物的分子量越低但反应进行得越快。在聚合过程中，分子量的变化都经历了一个先增加后下降的过程。引发剂pKa值越低、微波功率越高或引发剂用量越多，产物降解现象出现得越早。而且，产物分子量的下降总是出现在单体完全转化之后。模拟了反应混合体系中聚(ε-己内酯)在微波辐照下的降解行为。在无外加酸时，聚合物在微波辐照下就能发生降解；外加酸存在时，进一步促进了其降解，且酸性越强或用量越多，降解程度也越明显。 通过聚乙二醇引发ε-己内酯的微波开环聚合，制备了一系列分子量的聚(ε-己内酯)-聚乙二醇-聚(ε-己内酯)三嵌段共聚物，且其数均分子量可达到20000g／mol以上。聚合反应受到辐照时间、微波功率以及引发剂用量的影响：产物分子量和单体转化率均随着时间延长而逐渐增加；微波功率越高，单体转化率越高且分子量越大；引发剂用量越多，单体转化率越高但分子量越小。共聚物的分子量和化学组成可以通过聚乙二醇的用量及链长调控。考察了共聚物对布洛芬的体外释放行为，在载药量为5一20%时，药物都能持续且稳定地释放，遵循零级释放动力学，而且主要依照扩散的机理进行。聚乙二醇的引入，提高了聚(c一己内酷)的亲水性和限制了其结晶性能，从而影响共聚物对布洛芬的释放行为。 微波辐照下，季戊四醇能有效地引发。一己内酷开环聚合，得到的聚合物经傅里叶变换红外光谱(FT一IR)和核磁共振氢谱(’H一NMR)分析确证为星型聚(。-己内酷)，且每一臂上的数均分子量为300一3000 g/mol。微波功率越高或辐照时间越长，单体转化率越高，且聚合物分子量也越高。引发剂用量越多，单体转化得越快，但聚合物的分子量越低。通过调节季戊四醇的用量就可以有效地调控聚合物的分子量。微波辐照还能大大加快由此制备的星型聚(c一己内酷)与二酸配的交联反应，所得到的交联聚(。一己内酷)能在多种有机溶剂中溶胀，其热稳定性与星型聚(。一己内酷)相比有一定的提高。 研究了聚乙烯醇引发的今己内酷微波开环聚合，得到了一系列分子量的聚乙烯醇一接枝一聚(。一己内酷)共聚物，且聚(。一己内酷)支链的平均聚合度和取代度分别为3一24和0.35一0.89。共聚物的梳状结构经FT一IR、’H~NMR和粘度法确证。产物的示差扫描量热(DSC)分析和广角X一射线衍射(场人XD)分析表明，亲水性骨架聚乙烯醇的引入导致了接枝共聚物的熔点和结晶性能与线型的聚(。一己内酷)相比均有所下降。微波功率越高，单体转化率越高，聚(￡一己内酚)支链的平均聚合度和取代度都越高。随着辐照时间的延长，单体转化率和支链的聚合度均呈上升的趋势，而支链的取代度则先增加而后达到平衡。引发剂用量越多，单体转化得越快，但支链的平均聚合度以及取代度都越低。与常规加热聚合方式相比，微波加热明显促进了聚合的效果。更多还原

【Abstract】 Poly(ε-caprolactone)(PCL), used as a synthetic aliphatic polyester, was extensively investigated in the biomedicine field due to its high biodegradability, biocompatibility as well as drug permeability. In this paper the developments of PCL are reviewed involving the investigation on its catalyst or initiator system, functionalization and microwave synthesis.To improve in vivo biocompatibility and in vivo safety of PCL, exploring the effective nonmetallic catalyst or initiator system for the ring opening polymerization of ε-caprolactone (ε-CL) is being the hot topics in international research filed. This dissertation is focused on microwave-assisted ring opening polymerization (MROP) of ε-CL initiated by carboxylic acids and alcohols.The MROP of ε-CL initiated by benzoic acid was investigated. The product was confirmed to be PCL and the initiator residue was incorporated into the polymer chain. The weight-average molar mass (Mw) of PCL reached 44800 g/mol with polydispersity index (Mw/Mn) 1.6 when a reaction mixture of e-CL and benzoic acid was irradiated at 680W for 240 min. The influences of microwave power, irradiation time and initiator concentration on the polymerization were studied. The higher the power or the initiator concentration was, the higher Mw of product was in the beginning stage of the polymerization, but the lower maximum of Mw that could be obtained. Lasting irradiation time was beneficial to enhance the Mw. Microwave heating effect markedly influenced the polymerization reaction. The polymer chain propagated fast between 160 to 230C, within which the higher the temperature, the faster the propagation. However, when the temperature was over 230C, the chain propagation was limited and the resultant PCL degraded. The molar mass of microwave-produced PCL was significantly higher than that by conventional heating method. It was due to that microwave irradiation greatly inhibited formation of growing center at the beginning stage of the polymerization and ε-CL was consumed dominantly to lengthen the polymer chain, whereas ε-CL was mainly consumed to form growing centers in thermal polymerization. As a result, the polymer chain propagation was enhanced by microwaves.Three chlorinated acetic acid with different pKa, namely chloroacetic acid, dichloroacetic acid and trichloroacetic acid, were chosen to study the influence of acidity on MROP of ε-CL initiated by acids. Besides the microwave power, irradiation time and initiator concentration, the pKa of initiator obviously influenced the polymerization reaction. The lower the pKa of initiator was, the lower the molar mass ofthe resultant polymer was but faster the reaction proceeded. During the polymerization, the molar mass increased to a maximum first and then decreased. The lower pKa of initiator (higher power or more initiator) was, the earlier the degradation of PCL occurred. Moreover, the decrease in molar mass always began after the monomer was completely consumed. The degradation behavior of PCL in the reaction system was mimicked under microwave irradiation. It was revealed the degradation took place in the absence of the acid, and acid added to the system further favored the degradation. With the stronger or more acid, the extent of degradation was more obvious.A series of poly(?caprolactone)-poly(ethylene glycol)-poly(?caprolactone) triblock copolymers (PCECs) with number-average molar mass (Mn) over 20,000 g/mol were prepared, via the MROP of s-CL initiated by poly(ethylene alcohol) (PEG). The polymerization reaction was influenced by irradiation time, microwave power and the amount of initiator. With the reaction time increasing, both the molar mass and monomer conversion increased gradually. The higher the microwave power was, the higher the monomer conversion and the greater the Mn was. With more initiator, the monomer conversion was higher but lower Mn copolymer was obtained. The Mn and composition of the PCECs were expediently controlled by the amount and chain length of PEG in feed. The in vitro drug release behavi更多还原