聚丙烯酰多乙烯多胺系树脂的合成及对LDL的吸附性能研究
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摘要
在多孔聚合物基质上键连各种功能基得到的聚阴离子吸附剂，可以选择性地吸附清除血浆中的低密度脂蛋白成份，从而建立了安全、有效的治疗严重高脂血症和家族性高胆固醇血症的血液灌流治疗方法，文献中未能系统地研究基质结构、功能基种类、功能基数量及其分布状况对吸附剂吸附性能的影响规律。
我们以丙烯酸甲酯和异氰尿酸三烯丙酯悬浮共聚，制备了大孔交联聚丙烯酸甲酯，通过与乙二胺、二乙烯三胺、三乙烯四胺和四乙烯五胺等多乙烯多胺进行胺化反应得到了一系列大孔聚丙烯酰胺树脂，然后再分别与氯乙酸(溴乙酸)、亚磷酸和氯磺酸进行功能基化反应，得到了目的吸附剂。研究考察了基质结构、功能基性质、功能基数量等对吸附剂吸附血浆脂蛋白成分的性能的影响规律，获得了提高大孔型血浆低密度脂蛋白吸附剂的吸附容量和吸附选择性的方法。研究证实：(1)随着基质交联度的增加，吸附剂对低密度脂蛋白的吸附选择性降低：(2)功能基酸性越强，吸附剂对低密度脂蛋白吸附量和选择性越高；(3)提高功能基的数量有利于提高吸附剂对血浆低密度脂蛋白的吸附量和吸附选择性；(4)血浆低密度脂蛋白在聚阴离子型吸附剂上吸附作用，是吸附剂表面荷负电的功能基与血浆低密度脂蛋白表面荷正电的区域之间的静电相互作用。
初步考察了以大孔交联聚丙烯酰胺为基质的各种聚阴离子吸附剂的血液相容性，表明经过功能基化反应，吸附剂的血液相容性有所降低但仍有良好的血液相容性。
我们还研究合成了超高交联聚二乙烯基苯-异氰尿酸、凝胶型聚(苯乙烯-二乙烯基苯)-异氰尿酸和大孔交联聚(N-乙烯基乙酰胺)等三种不同类型的聚合物吸附剂，通过测定单宁在三种聚合物吸附剂上的等量吸附热，建立等量吸附热与吸附分数(定义为吸附量与单层饱和吸附量之比)之间的相关关系，研究探讨了三种聚合物吸附剂表面存在的能量不均匀性以及单宁的吸附热力学行为与吸附机理。
A safe and efficient therapy approach, so called LDL apheresis, which based on that polyanions covalently bound to porous polymer matrix can selectively adsorb low density lipoproteins (LDL) and very low density lipoproteins from human plasma, has been established for treating patients with severe hypercholesterolaemia or homozygous familial hypercholesterolaemia (FH). Despite the preparation methods and efficiency of various newly developed synthesized polyanion adsorbents for LDL apheresis have been extensively studied and reported, systematical reseajch results of the effects of porous polymeric matrix structures, the types of functional group, the amount and distribution patterns of the functional groups on the adsorption properties of polyanion adsorbents are rarely reported.
Macroporous crosslinked poly(methylacrylate-co-triallyisocyanuate) was synthesized by conventional suspension approach. Spherical macroporous N-substituted polyacrylamide was prepared via aminolysis reaction of the polyacrylate with aminolysis reagents, i.e. ethylenediamine, diethylenetriamine, triethylenetetramine and tetra-ethylenepentamine. A serious of polyanion adsorbents, bearing
f.
different acidic groups as functional groups, were synthesized by reacting with bromacetic acid, chloroacetic acid, phosphorous acid, and chlorosulfonic acid on spherical macroporous N-substituted polyacrylamide supporters. The influence rules of porous polymeric structures, the properties of functional groups and the amount of functional groups on the adsorption properties of the polyanion adsorbents were investigated in this work. The following conclusions were experimentally confirmed:
(1) The adsorption selectivity of concerned polyanion adsorbents for low density lipoproteins from human plasma decreases with the increase in crosslinking degree of the polymeric matrix. (2) Stronger acidity of the functional groups is, the higher adsorption capacity and
adsorption selectivity for LDL of the polyanion adsorbent will be. (3) To increase the amount and density of the functional groups on the adsorbent surface is beneficial to improve the LDL adsorption capacity and selectivity of polyanion adsorbent. (4) The static interaction of negative charged functional groups on the adsorbents surface with the positive charged domains on LDL particle plays a dominant role in the binding of polyanion adsorbents with LDL.
The blood compatibility of the polyanion adsorbents based on macroporous crosslinked polyacrylamide was preliminary explored as well. The bare matrix of macroporous polyacrylamide showed to be compatible well with blood. Functionalization of the matrix lowered the blood compatibility of the adsorbents at somewhat extent although blood compatibility of the functionalized adsorbents remained to be tolerable.
Three different polymeric adsorbents, hypercrosslinked poly (divinylbenzene-isocyanuric acid), gel-type crosslinked poly (styrene-isocyanuric acid) and crosslinked poly (N-vinyl acetamide) were prepared in this work as well. The isotherms of tannin adsorption from aqueous solution onto the three adsorbents were measured.
The thermodynamical behaviors of tannin adsorption were investigated. Based on Do's model, the isosteric enthalpy was quantitatively correlated with the fractional loading for tannin adsorption on the three polymeric adsorbents. The existence of surface energetic heterogeneities of the concerned polymeric adsorbents was reasonably expatiated. The adsorption mechanism of tannin on the concerned adsorbents was analyzed in detail.
我们以丙烯酸甲酯和异氰尿酸三烯丙酯悬浮共聚，制备了大孔交联聚丙烯酸甲酯，通过与乙二胺、二乙烯三胺、三乙烯四胺和四乙烯五胺等多乙烯多胺进行胺化反应得到了一系列大孔聚丙烯酰胺树脂，然后再分别与氯乙酸(溴乙酸)、亚磷酸和氯磺酸进行功能基化反应，得到了目的吸附剂。研究考察了基质结构、功能基性质、功能基数量等对吸附剂吸附血浆脂蛋白成分的性能的影响规律，获得了提高大孔型血浆低密度脂蛋白吸附剂的吸附容量和吸附选择性的方法。研究证实：(1)随着基质交联度的增加，吸附剂对低密度脂蛋白的吸附选择性降低：(2)功能基酸性越强，吸附剂对低密度脂蛋白吸附量和选择性越高；(3)提高功能基的数量有利于提高吸附剂对血浆低密度脂蛋白的吸附量和吸附选择性；(4)血浆低密度脂蛋白在聚阴离子型吸附剂上吸附作用，是吸附剂表面荷负电的功能基与血浆低密度脂蛋白表面荷正电的区域之间的静电相互作用。
初步考察了以大孔交联聚丙烯酰胺为基质的各种聚阴离子吸附剂的血液相容性，表明经过功能基化反应，吸附剂的血液相容性有所降低但仍有良好的血液相容性。
我们还研究合成了超高交联聚二乙烯基苯-异氰尿酸、凝胶型聚(苯乙烯-二乙烯基苯)-异氰尿酸和大孔交联聚(N-乙烯基乙酰胺)等三种不同类型的聚合物吸附剂，通过测定单宁在三种聚合物吸附剂上的等量吸附热，建立等量吸附热与吸附分数(定义为吸附量与单层饱和吸附量之比)之间的相关关系，研究探讨了三种聚合物吸附剂表面存在的能量不均匀性以及单宁的吸附热力学行为与吸附机理。
A safe and efficient therapy approach, so called LDL apheresis, which based on that polyanions covalently bound to porous polymer matrix can selectively adsorb low density lipoproteins (LDL) and very low density lipoproteins from human plasma, has been established for treating patients with severe hypercholesterolaemia or homozygous familial hypercholesterolaemia (FH). Despite the preparation methods and efficiency of various newly developed synthesized polyanion adsorbents for LDL apheresis have been extensively studied and reported, systematical reseajch results of the effects of porous polymeric matrix structures, the types of functional group, the amount and distribution patterns of the functional groups on the adsorption properties of polyanion adsorbents are rarely reported.
Macroporous crosslinked poly(methylacrylate-co-triallyisocyanuate) was synthesized by conventional suspension approach. Spherical macroporous N-substituted polyacrylamide was prepared via aminolysis reaction of the polyacrylate with aminolysis reagents, i.e. ethylenediamine, diethylenetriamine, triethylenetetramine and tetra-ethylenepentamine. A serious of polyanion adsorbents, bearing
f.
different acidic groups as functional groups, were synthesized by reacting with bromacetic acid, chloroacetic acid, phosphorous acid, and chlorosulfonic acid on spherical macroporous N-substituted polyacrylamide supporters. The influence rules of porous polymeric structures, the properties of functional groups and the amount of functional groups on the adsorption properties of the polyanion adsorbents were investigated in this work. The following conclusions were experimentally confirmed:
(1) The adsorption selectivity of concerned polyanion adsorbents for low density lipoproteins from human plasma decreases with the increase in crosslinking degree of the polymeric matrix. (2) Stronger acidity of the functional groups is, the higher adsorption capacity and
adsorption selectivity for LDL of the polyanion adsorbent will be. (3) To increase the amount and density of the functional groups on the adsorbent surface is beneficial to improve the LDL adsorption capacity and selectivity of polyanion adsorbent. (4) The static interaction of negative charged functional groups on the adsorbents surface with the positive charged domains on LDL particle plays a dominant role in the binding of polyanion adsorbents with LDL.
The blood compatibility of the polyanion adsorbents based on macroporous crosslinked polyacrylamide was preliminary explored as well. The bare matrix of macroporous polyacrylamide showed to be compatible well with blood. Functionalization of the matrix lowered the blood compatibility of the adsorbents at somewhat extent although blood compatibility of the functionalized adsorbents remained to be tolerable.
Three different polymeric adsorbents, hypercrosslinked poly (divinylbenzene-isocyanuric acid), gel-type crosslinked poly (styrene-isocyanuric acid) and crosslinked poly (N-vinyl acetamide) were prepared in this work as well. The isotherms of tannin adsorption from aqueous solution onto the three adsorbents were measured.
The thermodynamical behaviors of tannin adsorption were investigated. Based on Do's model, the isosteric enthalpy was quantitatively correlated with the fractional loading for tannin adsorption on the three polymeric adsorbents. The existence of surface energetic heterogeneities of the concerned polymeric adsorbents was reasonably expatiated. The adsorption mechanism of tannin on the concerned adsorbents was analyzed in detail.
引文
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