Fundamental Studies on Blood-Compatible Cellulose Membranes for Hemodialysis

最近，我们发现两种带相反电荷的纤维素衍生物之间形成的聚离子复合物（PIC）在体内和体外测试时显示出优异的血液相容性。在此发现的基础上，进一步尝试通过将PIC固定在其表面上来赋予用于血液透析的商业纤维素膜或中空纤维血液相容性。为此，纤维素膜或中空纤维的表面首先用缩水甘油基三甲基氯化铵（GTMAC）阳离子化，然后通过将膜或中空纤维浸入阴离子纤维素溶液中来实现PIC的形成。羧甲基纤维素和硫酸纤维素用作阴离子组分。通过体外模拟无肝素透析过程和测定活化血浆样品中补体消耗的程度，分别评价了改性膜和中空纤维的血液相容性和生物相容性。结果表明：（1）在最佳条件下用GTMAC处理，可有效地将阳离子基团引入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）用PIC进行表面改性是赋予纤维素中空纤维血液相容性而不改变渗透性能的有效手段。然而，在中空纤维上的结果的再现性不令人满意。目前正在努力提高再现性。

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.