【作者】 陈辉；

【导师】 鄢国平；

【作者基本信息】 武汉工程大学 ， 材料学， 2009， 硕士

【摘要】 生物医用材料是用于生物系统疾病的诊断与治疗、生物体组织或器官的修复或者替换,增进或恢复其功能的材料。其中可生物降解的高分子材料已广泛地用作药物控制释放的载体的研究。由于纳米材料颗粒极小,生物相容性好,在体内不易作为异物受到排斥。因此以可生物降解高分子为载体的纳米胶束和微球药物控制释放体系已成为国内外药学领域的研究热点。简要介绍可生物降解高分子的分类、合成以及应用,重点综述脂肪族聚碳酸酯和聚酯以及改性聚碳酸酯和聚酯在生物医用高分子材料中的应用。并概述了微波加热在高分子化学中的研究进展以及载药纳米胶束和微球的主要制备方法和药物控制释放系统的分类和发展现状。将环状碳酸酯单体9-苯基-2,4,8,10-四氧螺[5,5]十一烷-3-酮(2-phenyl -5,5 - bis (hydroxyl-methyl) trimethylene carbonate)与ε-己内酯(ε-Caprolactone)进行了常规加热开环共聚反应,制备了一系列侧链含苄氧基的脂肪族聚碳酸酯,然后用10%Pd/C对聚合物进行氢化还原脱保护,得到侧链含部分羟基的聚碳酸酯。羟基功能基团的引入,不仅增加了聚碳酸酯的亲水性与降解速率,而且有利于化学结合肿瘤靶向基团与药物以及进行其他化学修饰。通过控制单体的投料比合成不同组成的碳酸酯共聚物,进一步调节聚碳酸酯的亲水-疏水性能与降解速率。对所得聚合物进行1H NMR、GPC、FT-IR、DSC、UV、Water Contact Angle等结构表征。体外降解实验表明部分脱保护的碳酸酯共聚物比未脱保护的碳酸酯共聚物有着更好的亲水性和较快的降解速率,两类共聚物都有稳定的释药速率和良好的药物控制释放性能,相对于未脱保护的共聚物来说,还原后的共聚物有更快的释药速率。将PTC与CL采用微波加热方法进行微波开环共聚反应。研究了单体投料比,引发剂用量,微波聚合功率,微波聚合温度,微波辐照时间对聚合物的影响。对所得聚合物进行1H NMR、GPC、FT-IR、DSC、UV、Water Contact Angle等结构表征。体外降解实验表明共聚物降解缓慢,疏水性强。体外释药实验表明共聚物具有稳定的释药速率和良好的药物控制释放性能。通过两步反应将肿瘤靶向基团磺胺嘧啶引入到可生物降解的部分还原的碳酸酯共聚物中,合成肿瘤靶向性药物载体。分别采用透析法和高压电场电雾化法制备纳米靶向抗癌药物。并对其形貌尺寸进行了表征,初步研究了纳米药物的体外控制释药性能。更多还原

【Abstract】 Biomedical materials are used for the diagnosis and treatment of diseases, repairing and replacement of the tissue and organ, to improve or recover the function. The biodegradable polymer materials, can be widely used as the carriers of the drug controlled release systems. Recently, the nano-micelles and nano-particles drug delivery system based on the biodegradable polymers as the carriers have attracted the attention in the pharmacy filed, because nano materials possess the minimal particle size, good biocompatibility and can be reasily to pass through the organ and not be rejected as foreign body.Briefly reports were done about the categories, synthesis and application of the biodegradable polymers in the first chapter. In addition, the application of aliphatic polycarbonate, polyester and modified polycarbonate and polyester in polymeric biomedical materials were reported subsequently, research progress of microwave heating in polymer chemistry was overviewed. The development trend of drug controlled release systems and the preparation methods of drug-loaded nano-micelles and nano-microparticles were described in detail here.A series of polycarbonate copolymers were synthesized by the ring-opening bulk polymerization ofε-caprolactone (CL) and 2-phenyl-5,5-bis(hydroxymethyl) trimethylene carbonate (PTC) with Tin (II) 2-ethylhexanoate as an initiator. These polycarbonate copolymers were further reduced by the palladium/carbonate (Pd/C) catalyst to obtain the partly deprotected polycarbonate copolymers. These two type copolymers obtained were characterized by 1H NMR, FT-IR, UV, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and automatic contact angle meter. The influences of the feed molar ratio of monomers, initiator concentration and reaction time as well as reaction temperature on the copolymerization process were also studied. The copolymerization of CL and PTC monomers was a non-ideal copolymerization and the copolymerization reactivity ratio of CL was higher than that of PTC in the polymerization process. In vitro degradation tests indicated that partly deprotected polycarbonate copolymers possess the faster degradation rates and more hydrophilicity than those of unreduced polycarbonate copolymers. In vitro release profiles of 5-Fu from copolymers showed that these two type copolymers have the steady drug release rates and nice controlled release properties. Moreover, partly deprotected polycarbonate copolymers have faster drug release rates than those of unreduced polycarbonate copolymers.A series of polycarbonate copolymers were synthesized by microwave-assisted ring-opening polymerization ofε-caprolactone (CL) and 2-phenyl-5,5-bis(oxymethyl) trimethylene carbonate (PTC) with Tin (II) 2-ethylhexanoate as an initiator. These copolymers obtained were characterized by 1H NMR, FT-IR, UV, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and automatic contact angle meter. The influences of the feed molar ratio of monomers, initiator concentration, reaction time and reaction temperature, as well as microwave irradiation power on the copolymerization process were also studied. In vitro degradation tests indicated that these polycarbonate copolymers possess the slow degradation rates and strong hydrophobicity. In vitro release profiles of 5-Fu from copolymers showed that copolymers have the steady drug release rates and nice controlled release properties.Sulfadiazine as the tumor targeting group was incorporated into the biodegradable partly deprotected polycarbonate copolymers to give the tumor-targeting drug delivery carriers. Drug-loaded polymer nano-micelles or nano-particles were prepared by the methods of dialysis and high voltage electric atomization. The particle size and morphology of drug-loaded nanometerials and drug release properties in vitro were also studied.更多还原