两亲性环状高分子的设计、合成及应用研究

发布时间：2018-05-04 12:29

本文选题：环状聚合物 + 点击化学　；参考：《安徽大学》2017年硕士论文

【摘要】：目前,具有拓扑结构的环状高分子是高分子研究的一个热点。与线形聚合物相比,环状高分子具有比较特殊的性质,如热稳定性、化学稳定性的提高,流体动力学体积的减小等等。一般来说,线形聚合物在作为生物医用组织工程材料时表面比较光滑,生物相容性较差,会造成严重的组织反应,而拓扑结构聚合物材料的表面比较粗糙,像海绵状、纤维状等等,生物相容性较好,因此环状拓扑结构聚合物材料在生物医用领域有很大的应用前景。但环状聚合物合成过程复杂、端基官能团反应活性低,使环状拓扑结构聚合物的合成与结构表征工作复杂且极具挑战性。而活性自由基聚合的链末端高活性和"点击"化学的高选择性相结合可以大大解决这个问题,其中以原子转移自由基活性聚合(ATRP)与一价铜盐催化的炔基/叠氮偶极环加成反应(CuAAC)相结合的方法最为典型,使其越来越备受关注。本文的研究内容主要包含:第一章简要地介绍了环状聚合物的结构、性质和合成方法,重点阐述了几种点击化学与活性聚合联用制备环状聚合物的方法,其中以"点击"化学中的一价铜盐催化的炔基/叠氮偶极环加成反应(CuAAC)与原子转移自由基活性聚合(ATRP)联用的方法适用范围更广,产率较高,实验操作最简单。进一步阐明了两亲性环状聚合物胶束的制备方法以及近几年来两亲性环状聚合物胶束的国内外研究现状。第二章结合原子转移自由基活性聚合(ATRP)和"点击"化学中铜盐催化的炔基/叠氮偶极环加成(CuAAC)反应,可控合成两亲性环状聚(ε-己内酯-b-乙烯基吡咯烷酮)嵌段共聚物(Cyclic-PCL-b-PVP),通过傅立叶变换红外光谱(FT-IR)、核磁共振氢谱(1H-NMR)和凝胶渗透色谱(GPC)分别表征聚合物的结构、分子量及分子量分布,表明两亲性Cyclic-PCL-b-PVP的成功合成。利用热重分析(TGA)、接触角和X射线衍射(XRD)的测试,分别研究了两亲性嵌段共聚物的热学性能、亲水性能和结晶性能,结果表明,相比于线形聚(ε-己内酯-b-乙烯基吡咯烷酮)嵌段共聚物(Linear-PCL-b-PVP),相应的环状嵌段共聚物的热稳定性明显提高,亲水性和结晶性能亦有所变化。第三章主要利用第二章合成的产物环状Cyclic-PCL-b-PVP嵌段共聚物用透析法进行自组装成为胶束聚集体,并将其作为药物载体对吲哚美辛药物进行负载,用芘荧光探针、马尔文纳米激光粒径仪和透射电子显微镜(TEIM)分别测定了线状、环状PCL-b-PVP嵌段共聚物的临界胶束浓度(CMC)、胶束的粒径和形貌,结果表明线状、环状PCL-b-PVP嵌段共聚物的CMC均较小,得到的胶束稳定性良好;相比于线形聚合物胶束的粒径,由于成环后无分子链末端,聚合物链排列较为规整和紧密,使环状Cyclic-PCL-b-PVP嵌段共聚物胶束的粒径较小。从TEM图中可以明显看出PCL-b-PVP嵌段共聚物胶束基本呈现球形,载药后的嵌段共聚物胶束粒径相对较大,这是由于成功包载药物的缘故。第四章采用ATRP和"点击"化学中的CuAAC相结合的方法,可控合成了环状聚(ε-己内酯-b-(N-异丙基丙烯酰胺))(Cyclic-PCL-b-PNIPAM)温敏性嵌段共聚物。采用FT-IR、1H-NMR和GPC方法表征了其共聚产物的结构、分子量及分子量分布。用TGA、DSC、接触角和XRD的方法,研究了环状嵌段共聚物的热稳定性、温敏性、亲水性和结晶性能的变化。相比于PCL-b-PNIPAM线形嵌段共聚物,由于聚合物成环后无分子链末端,其链的解聚较为困难,则相应的热稳定性提高;PNIPAM温敏性链段的相转变温度表现为37.5℃;亲水性和结晶性亦有所变化。第五章主要利用第四章成功合成的产物温敏性环状Cyclic-PCL-b-PNIPAM嵌段共聚物用透析法进行自组装形成胶束聚集体,并将其作为药物载体对吲哚美辛药物进行负载,用芘荧光探针、马尔文纳米激光粒径仪和TEM的方法分别测定了线状、环状PCL-b-PNIPAM嵌段共聚物的CMC、胶束的粒径和形貌,研究表明:线状、环状PCL-b-PNIPAM嵌段共聚物的CMC均较小,得到的胶束稳定性良好;相比于线形聚合物前体胶束的粒径,由于成环后无分子链末端,聚合物链排列较为规整和紧密,使Cyclic-PCL-b-PNIPAM共聚物胶束的粒径较小;TEM结果表明PCL-b-PN][PAM嵌段共聚物胶束基本呈现球形,载药后的嵌段共聚物胶束由于成功包载了吲哚美辛药物,其粒径相对较大。
[Abstract]:At present, circular polymers with topological structures are a hot topic in the study of polymer. Compared with linear polymers, circular polymers have special properties, such as thermal stability, chemical stability, and the decrease of the volume of fluid dynamics. Generally speaking, linear polymers are on the surface of biomedical engineering materials. The smooth and poor biocompatibility will cause serious tissue reaction, and the surface of the topological polymer material is rough, such as spongy, fibrous and so on, and the biocompatibility is good. Therefore, the ring topology polymer material has a great application prospect in the biomedical field, but the ring polymer synthesis process is complex and the end group is complex. The low reactive activity of functional groups makes the synthesis and structural characterization of a cyclic topological polymer complex and challenging. The combination of the high activity of the terminal chain at the end of the active radical polymerization and the high selectivity of "click" chemistry can greatly solve this problem, in which the atom transfer radical active polymerization (ATRP) is catalyzed by the monovalent copper salt. The method of combining alkynyl / AZO dipolar cycloaddition reaction (CuAAC) is the most typical one, making it more and more concerned. The main contents of this paper include: in the first chapter, the structure, properties and synthesis methods of cyclic polymers are briefly introduced, and several methods for the preparation of cyclic polymers by clicking chemistry and active polymerization are emphasized. The method of combination of alkynyl / AZO dipole ring addition reaction (CuAAC) with atom transfer radical active polymerization (ATRP) catalyzed by one valence copper salt in "click" chemistry is more widely used, the yield is higher, and the experimental operation is the simplest. The preparation method of two amphiphilic ring polymer micelles and the amphiphilic ring polymerization in recent years are further clarified. The second chapter controlled the synthesis of two amphiphilic cyclic poly (caprolactone -b- vinylpyrrolidone) block copolymers (Cyclic-PCL-b-PVP) by combining atomic transfer free radical active polymerization (ATRP) and "clicking" chemical copper salts catalyzed alkynyl / AZO dipole cycloaddition (CuAAC) reaction, and the infrared light was transformed by Fu Liye transformation. Spectrum (FT-IR), nuclear magnetic resonance hydrogen spectrum (1H-NMR) and gel permeation chromatography (GPC) were used to characterize the structure, molecular weight and molecular weight distribution of the polymer respectively, indicating the successful synthesis of two Pro Cyclic-PCL-b-PVP. The thermal properties and hydrophilicity of the two amphiphilic block copolymers were investigated by thermogravimetric analysis (TGA), contact angle and X ray diffraction (XRD). The results show that the thermal stability of the corresponding ring block copolymer is obviously improved and the hydrophilic and crystalline properties are also changed compared to the linear poly (epsilon caprolactone -b- vinylpyrrolidone) block copolymer (Linear-PCL-b-PVP). The third chapter mainly uses the product ring Cyclic-PCL-b-PVP block copolymerization in second chapters. The products were self assembled into micellar aggregates and loaded with indomethacin as drug carriers. A pyrene fluorescent probe, Malvin nano laser particle size analyzer and transmission electron microscope (TEIM) were used to determine the critical micelle concentration (CMC) of a linear, circular PCL-b-PVP block copolymer, the particle size and morphology of the micelle, and the junction of the micelle. The CMC of the ring PCL-b-PVP block copolymer is smaller and the stability of the micelle is good. Compared to the particle size of the linear polymer micelle, the polymer chain is more regular and compact because of the ring free chain end after the ring formation. The particle size of the circular Cyclic-PCL-b-PVP block copolymer micelle is smaller. It can be clearly seen from the TEM diagram. The PCL-b-PVP block copolymer micelles are basically spherical, and the size of the block copolymer micelles after drug loading is relatively large, which is due to the successful loading of the drug. The fourth chapter uses the method of combining the ATRP and the CuAAC in "click" chemistry to synthesize the cyclic poly (epsilon hexyl -b- (N- isopropyl acrylamide)) (Cyclic-PCL-b-PNIPAM) temperature The structure, molecular weight and molecular weight distribution of the copolymers were characterized by FT-IR, 1H-NMR and GPC methods. The thermal stability, temperature sensitivity, hydrophilic and crystalline properties of the ring block copolymers were studied by means of TGA, DSC, contact angle and XRD. Compared to the linear block copolymers of PCL-b-PNIPAM, the polymers were compared with those of the polymer. The depolymerization of the chain is more difficult and the thermal stability of the chain is more difficult. The phase transition temperature of the PNIPAM Wen Min sex segment is 37.5, and the hydrophilicity and crystallinity are also changed. The fifth chapter mainly uses the dialysis method for the thermo sensitive cyclic Cyclic-PCL-b-PNIPAM block copolymer of the products synthesized in the fourth chapters. The micellar aggregates were formed by self assembly and used as drug carriers to load indomethacin. The CMC of linear, ring PCL-b-PNIPAM block copolymers and the size and morphology of the micelles were measured with pyrene fluorescence probe, Malvin nano laser particle size meter and TEM, respectively. The study showed that the linear, circular PCL-b-PNIPAM block copolymer was linear. Compared to the particle size of the linear polymer precursor micelles, the size of the CMC micelles is relatively small and the particle size of the Cyclic-PCL-b-PNIPAM copolymer micelles is relatively small compared to the particle size of the linear polymer precursor micelles. The TEM results show that the PCL-b-PN][PAM block copolymer micelles are basically spherical and after the drug loading. Micelles of block copolymers were successfully coated with indomethacin, and their diameters were relatively large.

【学位授予单位】：安徽大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O631;TQ460.1

【参考文献】