【作者】 苏秋香；

【导师】 周绍兵；

【作者基本信息】 西南交通大学 ， 材料物理与化学， 2008， 硕士

【摘要】 近年来,生物可降解高分子材料被广泛应用于药物控释体系、可吸收缝合线、外科矫形器件、细胞组织工程等生物医用领域。聚酸酐作为一类具有良好生物相容性、表面溶蚀特性及降解速度可调的生物降解性高分子材料,倍受人们关注。到目前为止,人们合成了各种类型的聚酸酐,然而在药物控释领域应用最多的实际上是由不同单体按照一定比例聚合而成的各种酸酐共聚物。这主要是因为:一方面随着聚酸酐在药物控释领域应用的不断扩展,单独的聚酸酐均聚物很难满足药物控释要求,仅靠其分子量和分子量分布调节降解速度具有很大的局限性;另一方面为了进一步改进冲击强度、渗透性及亲水性,人们开始对聚酸酐骨架进行修饰,引入其它聚酸酐或其它可降解高分子材料形成各类共聚物,改进聚酸酐的性能,以更好地满足药物控释的要求。本文也在这方面做了研究,包括以下主要内容:1.以癸二酸（SA）和合成单体1,3-双对羧基苯氧基丙烷（CPP）为起始原料,采用熔融缩聚法合成了一系列具有不同共聚组成比的脂肪族—芳香族共聚酸酐P（CPP-SA）。考察了反应温度和反应时间等对聚酸酐分子量的影响。研究结果表明,在实验室条件下,最佳的聚合条件为:真空度55mmHg,反应温度为180℃下聚合2h,合成的聚酸酐粘均分子量最高可达60,000左右。所得的聚酸酐用FT-IR、¹H NMR、粘度法、DSC及XRD进行了表征,实验结果表明合成的聚酸酐具有分子量高,熔点低,热稳定性好等特点。利用变温红外研究了聚酸酐P（CPP-SA）（20:80）的热稳定性及其结晶相关谱带,结果发现:PSA链段的稳定性比PCPP链段的稳定性差;1471,1412,1359cm^-1三个谱带在变温过程中表现得很特别,推测其与聚酸酐的结晶相关联,可能是其结晶相关谱带。2.采用了熔融缩聚法合成了SA、CPP、PEG三元醚酐共聚物及SA、F127二元醚酐共聚物。¹H NMR和FTIR证实了单体、预聚物及无规共聚物的结构。理化性质表征结果显示:合成的醚酐共聚物具有分子量高,熔点较低,热稳定性较好等作为药物缓释材料必备的性能。同时研究发现PEG的引入对聚酸酐的分子量、结晶度及亲水性有较大影响。3.以P（CPP-SA）共聚酸酐为载体材料,采用静电纺丝技术制备了未载药的及载有模型药物对乙酰氨基酚的纤维膜,体外降解研究表明,聚酸酐P（CPP-SA）在前期的降解速度特别快,一天内重量损失就达到了50%左右,而后期是一个比较缓慢的降解。且随着聚酸酐中疏水性单体CPP含量的增加,降解速度减慢,这些结果表明了聚酸酐的降解与聚酸酐的组成及基质的几何形状大小密切相关。体外释放研究表明,聚酸酐的溶蚀是控释的机理。药物释放初期产生了一个明显的突释过程,突释量达到了45%左右,而后是一个缓释过程。更多还原

【Abstract】 In recent years, biodegradable polymeric materials have been found to be useful in drug delivery, absorbable suture, surgical orthopedic device and cell tissue engineering applications. In these materials, polyanhydride was a kind of biodegradable polymer, which attracted the interest of many researchers, because it was biocompatible, surface-eroding behavior and the rate of degradation was adjustable. Up to now, many types of polyanhydrides have been synthesized, but in the controlled drug delivery systems, the most wide use of application is the copolymers which are synthesized by different monomer ratios. The main cause include two parts. On the one hand, with the increasing application of controlled drug delivery systems, polyanhydride homopolymer can not meet requirement for drug delivery. To adjust the rate of degradation only depend on molecular weight and molecular weight distribution of copolymers have limitation. On another hand, in order to improve impact strength, permeability and hydrophilicity, other polyanhydrides or biodegradable polymeric materials are incorporated into the polymer backbone, which improve the performance of polyanhydride to meet requirement for drug delivery. This paper also research in this respect, the main results are as follows:1. The biodegradable polyanhydride copolymers composed of p-carboxyhenoxy propane （CPP） and sebacic acid （SA） in different weight ratios were polymerized by a melt polycondensation process. Additionally, several factors which affected the molecular weight had been studied, such as reaction time, reaction temperature and so on. The optimized conditions under laboratory conditions were vacuum degree 55mmHg, reaction temperature 180℃and reaction time 2h. The copolymers were characterized by FT-IR, ¹H NMR, Ubbelohde viscometer, differential scanning calorimetry （DSC） and X-ray diffraction （XRD） etc. It show that all the prepared polyanhydrides possesses high molecular weights, low melting points, and desired thermal stability. It was found that PCPP chain segment exhibit more stable than PSA after being investigated by FTIR spectra between 24-300℃. The peaks of 1471, 1412, 1359 cm^-1 changed sharply after 70℃in this process. It was deduced that these three peaks are linked to the crystalline of P（CPP-SA）.2. A series of biodegradable poly（ether-anhydrides） composed of poly（ethyleneglycol）（PEG）, and 1,3-bis（carboxyphenoxy）propane（CPP）, sebacic acid（SA）, or PluronicF127 and sebacic acid（SA） were synthesized by a melt polycondensation process. Characterization of the copolymers by FTIR and ¹H NMR confirms their structures. The physical and chemical properties showed that all the prepared poly（ether-anhydrides） meet the essential requirement for polyanhydrides as drug delivery material including high molecular weights, low melting points, and desired thermal stability. Meanwhile, the research shows that PEG blocks existed has great influence on molecular weight, crystallinity and hydrophilicity of polyanhydride.3. Copolymer ultrafine fibers, which contain paracetamol as a model drug and P（CPP-SA） were prepared by electrostatic spinning. The experimental results showed that degradation rate was fast in the fist day and slowed in the following period, furthermore the degradation rate decreased with the increase of the content of CPP in copolymers. These results reveal the degradation is closely related to copolymer composition and geometry of matrice. In vitro release study showed that polyanhydride erosion is the mechanism of drug controlled release. There was an initial burst release about 45% and sustained released in the following period.更多还原