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作为用于血液透析的血液相容性膜材料的纤维素氨基甲酸酯及其衍生物。

Cellulose carbamates and derivatives as hemocompatible membrane materials for hemodialysis.

作者信息

Diamantoglou M, Platz J, Vienken J

机构信息

Akzo Nobel Central Research, Obernburg, Germany.

出版信息

Artif Organs. 1999 Jan;23(1):15-22. doi: 10.1046/j.1525-1594.1999.06272.x.

Abstract

Dialysis membranes made from regenerated cellulose are under dispute because of their alleged lack of hemocompatibility. The introduction of membranes from synthetically modified cellulose, like cellulose acetate or Hemophan, has proven, however, that hemocompatible membranes can be fabricated from cellulose by means of chemical surface modifications. In addition to membranes made from modified cellulose like ethers or esters, which were investigated in earlier experiments, we looked for further cellulose modifications to be assessed for their hemocompatibility. For this purpose, we synthesized a series of cellulose carbamate derivatives to profit from the excellent hemocompatibility pattern of the urethane family. In vitro investigations on membranes made from these cellulose modifications proved a direct relationship between the degree of modification and hemocompatibility. This was proven for the following 3 representative hemocompatibility parameters: complement C5a generation, thrombin-antithrombin (TAT) III formation, and platelet count (PC). As already shown for modifications made from cellulose esters, a direct dependency between improved hemocompatibility and the degree of substitution (DS) in the cellulose molecule could be found. In our experiments, a degree of substitution below a value of 0.1 led to a nearly complete suppression of complement activation for all cellulose carbamates under investigation. In contrast to data on cellulose esters, we observed that molecular weight or molecular conformation of chemical substituents exerted only a minor effect on the hemocompatibility pattern. In addition, data on cellulose carbamate esters (e.g., cellulose succinate-phenyl-carbamate) show that a simultaneous but balanced substitution with hydrophilic and hydrophobic groups at the surface of the cellulose polymer is a further prerequisite for optimal hemocompatibility. It seems that the carbamate configuration per se has a positive effect on the hemocompatibility pattern of synthetically modified cellulose membranes.

摘要

由再生纤维素制成的透析膜因据称缺乏血液相容性而备受争议。然而,引入由合成改性纤维素制成的膜,如醋酸纤维素或Hemophan,已证明可以通过化学表面改性由纤维素制造出血液相容性良好的膜。除了早期实验中研究的由醚或酯等改性纤维素制成的膜外,我们还寻找了其他纤维素改性方法来评估其血液相容性。为此,我们合成了一系列纤维素氨基甲酸酯衍生物,以利用聚氨酯家族优异的血液相容性模式。对由这些纤维素改性制成的膜进行的体外研究证明了改性程度与血液相容性之间存在直接关系。这在以下3个代表性的血液相容性参数中得到了证明:补体C5a生成、凝血酶 - 抗凝血酶(TAT)III形成和血小板计数(PC)。正如已经在纤维素酯改性中所显示的那样,在纤维素分子中可以发现改善的血液相容性与取代度(DS)之间存在直接相关性。在我们的实验中,对于所有研究的纤维素氨基甲酸酯,取代度低于0.1的值会导致补体激活几乎完全受到抑制。与纤维素酯的数据相反,我们观察到化学取代基的分子量或分子构象对血液相容性模式仅产生轻微影响。此外,纤维素氨基甲酸酯的数据(例如纤维素琥珀酸 - 苯基 - 氨基甲酸酯)表明,在纤维素聚合物表面同时但平衡地用亲水和疏水基团进行取代是实现最佳血液相容性的另一个先决条件。似乎氨基甲酸酯构型本身对合成改性纤维素膜的血液相容性模式具有积极影响。

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