【作者】 张红；

【导师】 谭业邦；

【作者基本信息】 山东大学 ， 高分子化学与物理， 2013， 硕士

【摘要】 高血脂病严重威胁到人们的身体健康,其最主要的发病原因是血液中胆固醇含量过高。在目前使用的降血脂药物中,最为常用的就是胆酸螯合剂类,其降低血脂的机理是在肠道中与胆汁酸螯合并促进其排除体外,从而加快胆固醇向胆酸的转化,从而降低血液中的胆固醇浓度。通过对比目前上市的和处在研发阶段的胆酸螯合剂可以发现,在设计胆酸螯合剂的时候遵循以下几个原则：(1)高电荷密度；(2)分子结构中带有疏水结构；(3)在水中具有良好的溶胀能力。据此,本论文设计合成了三个烯丙基胺类聚合物体系,并对这些聚合物的结构性质进行了研究。(1)以烯丙基胺盐酸盐与二甲基二烯丙基氯化铵为原料通过过硫酸钾引发进行自由基聚合制备聚(烯丙胺盐酸盐／二甲基二烯丙基氯化铵)(PAH/DMDAAC)共聚物,对聚合物的结构和热稳定性进行了表征。用静态光散射测定了聚合物的分子量,利用共振光散射研究了聚合物的水溶液性质。将聚合物与牛血清蛋白相互作用,通过荧光光谱及圆二色光谱仪研究了其对蛋白质的荧光猝灭效果以及对蛋白质的构象影响,证实了聚合物对于蛋白质的猝灭机制是动态猝灭,且聚合物的加入会对蛋白质的a螺旋产生一定程度的破坏。采用糠醛比色的方法利用标准曲线得到了聚合物对于脱氧胆酸钠的螯合效果。(2)通过烯丙基胺与溴代正辛烷反应然后用盐酸中和,得到烷基改性的辛基烯丙胺盐酸盐,然后将其与二甲基二烯丙基氯化铵共聚,得到共聚物聚(辛基烯丙胺盐酸盐／二甲基二烯丙基氯化铵)(POAH/DMDAAC),通过核磁共振、红外光谱、热重分析等手段对聚合物进行了表征。利用静态光散射测定了聚合物的分子量,用动态光散射研究了浓度、pH值、外加盐对聚合物的水溶液的影响,发现聚合物的流体力学半径随着浓度的增大而增大且分布变宽,随着pH的增大而增大。将聚合物溶液与牛血清蛋白相互作用,通过荧光光谱及圆二色光谱仪研究了其对蛋白质的荧光猝灭效果以及对蛋白质的构象影响。采用糠醛比色的方法利用标准曲线得到了聚合物对于脱氧胆酸钠的吸附效果。(3)通过三烯丙胺与烯丙胺盐酸盐进行共聚,得到部分交联的共聚物,通过红外光谱和热重分析对其结构进行了基本的表征。利用共振光散射研究了浓度和pH值的变化对其在水溶液聚集形态的影响,并研究了其对脱氧胆酸钠的螯合作用。更多还原

【Abstract】 Hyperlipidemia has been a threaten for healthy for many years, and it is belived that cholesterol raise result in Hyperlipidemia. Bile acid sequestrant, a kind of widely used lipid-lowering drug,it may chelate with bile acid in intestine to promote excretion, so increase cholesterol transform to bile acid, then concertration of cholesterol in blood decreased. According to the structure of the bile acid sequestrant on sale and in research stage, structural features of potential BAS in general comprise of an optimum combination of charge density, hydrophobic, and water swelling properties. According to this,three kind of copolymers are synthesized:(1) The copolymers PAH/DMDAAC were synthesized by the copolymerization of allylamine hydrochloride (AH) with N,N-dimethyl-N,N-diallyl ammonium chloride (DMDAAC). The structure,thermal stability and molecular weight of PAH/DMDAAC were characterized by1HNMR, infrared spectroscopy thermogravimetric analysis and stastic light scattering. The aggregation behavior of PAH/DMDAAC in aqueous solution were studied by resonance scattering spectral measurements.. The interaction between PAH/DMDAAC and bovine serum albumin in aqueous solution were studied by fluorescence and circular dichroism(CD) spectra. The chelation of copolymer with bile acid in solution were measured by UV-Vis with the method of futural colorimetric.(2) N-octane allylamine hydrochloride (OAH) was obtained by reaction of n-bromooctane with allylamine and then neutralized with hydrochloride. The copolymer POAH/DMD AAC were synthesized by the copolymerization of N-octane allylamine hydrochloride (OAH) with N,N-dimethyl-N,N-diallyl ammonium chloride(DMDAAC). The structure,thermal stability and molecular weight of POAH/DMD AAC were characterized by1HNMR, infrared spectroscopy, thermogravimetric analysis and stastic light scattering. The aggregation behavior of of POAH/DMD AAC in aqueous solution were studied by dynamic light scattering. The interaction between POAH/DMD AAC and bovine serum albumin in aqueous solution were studied by fluorescence and circular dichroism spectra. The chelations of these copolymers with bile acid were measured by UV-Vis with the method of futural colorimetric.(3) The cross-linked polymers were prepared by the copolymer of allylamine hydrochloride with triallylamine hydrochloride. The structure of this copolymer was confirmed by Infrared spectroscopy and thermogravimetric analysis. The solution properties of the cross-linked polymers by resonance scattering spectral measurements. The chelation of copolymers with bile acid in solution were measured by UV-Vis and colorimetric method.更多还原