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Fundamental Studies on Blood-Compatible Cellulose Membranes for Hemodialysis

血液透析用血液相容性纤维素膜的基础研究

基本信息

批准号：
62890006
负责人：
MIYAMOTO Takeaki
金额：
$ 3.71万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Recently, we have found that polyion complexes (PICs) formed between two oppositely charged cellulose derivatives show an excellent blood compatibility when tested in vivo as well as in vitro. On the basis of this finding, further attempt was made to impart the blood compatibility to commercial cellulose membrances or hollow fibers used for hemodialysis by immobilizing the PIC on their surfaces. For the purpose, the surface of cellulose membrances or hollow fibers was first cationized with glycidyl trimethylammonium chloride (GTMAC) and then the PIC formation was realized by immersing the membrances or hollow fibers in an anionic cellulose solution. Carboxymethyl cellulose and cellulose sulfate were used as the anionic component. Blood compatibility and biocompatibility of modified membrances and hollow fibers were evaluated by the ex vivo method simulating the dialysis procedure without heparin and by assaying the extent of complement consumption in activated plasma samples, respectively. Permeability experiments were carried out by the usual method.It was found that (1) when treated with GTMAC under the optimum conditions, the cationic groups were effectively introduced to the inner surface of membrances and hollow fibers without causing any prominent changes in mechanical properties, (2) the PIC-modified membrances and hollow fibers suppress the activation of the complement system, and (3) the surface modification with PIC is an effective means for imparting blood compatibility to cellulosic hollow fibers without bringing any changes in the permeation properties. However, the reproducibility of the results on hollow fibers was not satisfactory. Attempts to improve the reproducibility are now in progress.

最近，我们发现两个相反电荷的纤维素衍生物之间形成的多离子络合物(PIC)在体内和体外测试时都显示出良好的血液相容性。在这一发现的基础上，进一步尝试通过将PIC固定在商业纤维素膜或用于血液透析的中空纤维的表面来赋予其血液相容性。为此，首先用缩水甘油基三甲基氯化铵(GTMAC)对纤维素膜或中空纤维表面进行阳离子处理，然后将纤维素膜或中空纤维浸泡在阴离子纤维素溶液中形成PIC。以羧甲基纤维素和硫酸纤维素为阴离子组分。分别采用模拟无肝素透析过程的体外方法和测定活化血浆中补体消耗程度的方法评价改性膜和中空纤维的血液相容性和生物相容性。采用常规方法进行渗透实验，结果表明：(1)在最佳条件下，GTMAC能有效地将阳离子基团引入到膜和中空纤维的内表面，而不会引起力学性能的显著变化；(2)PIC改性膜和中空纤维抑制了补体系统的活化；(3)PIC表面改性是一种在不改变渗透性能的情况下赋予纤维中空纤维血液相容性的有效手段。然而，在中空纤维上的结果的重复性并不令人满意。改善重现性的尝试目前正在进行中。