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合成改性纤维素:用于血液透析的合成膜替代品?

Synthetically modified cellulose: an alternative to synthetic membranes for use in haemodialysis?

作者信息

Hoenich N A, Woffindin C, Stamp S, Roberts S J, Turnbull J

机构信息

Department of Medicine, University of Newcastle, Newcastle upon Tyne, UK.

出版信息

Biomaterials. 1997 Oct;18(19):1299-303. doi: 10.1016/s0142-9612(97)00062-8.

Abstract

Renal replacement therapy relies predominantly on the use of cellulose-based membranes. Such membranes have a biocompatibility profile which is inferior to membranes manufactured from synthetic polymers. Synthetically modified cellulose (SMC) is a new, low-flux haemodialysis membrane in which hydroxyl groups have been replaced with benzyl groups. The biocompatibility profile characterized by changes in white cell and platelet counts and the activation of complement components (C3a, C5a and C5b-9) have been studied in vivo and compared with those of cellulose acetate, unmodified cellulose (Cuprophan ) and low-flux polysulphone (Fresenius Polysulfone) in the same group of patients. For SMC, the white cell count at 15 min declined to 65.6% of pretreatment level, compared with 63.8% for the cellulose acetate, 79.6% for low-flux polysulphone and 28.1% for Cuprophan, thereafter returning to pretreatment levels. Both modified cellulose membranes were superior to unmodified cellulose (P = 0.001); the differences between the modified cellulose membranes were not significant statistically. The changes induced by all three cellulose-based membranes exceeded those for low-flux polysulphone (P = 0.001). Associated with the neutropenia was a reduction in platelet count, but this was independent of membrane type. The mean time-averaged concentrations of C3a(des Arg) over 150 min were 1168 ng ml(-1) (SMC), 1030 ng ml(-1) (cellulose acetate), 1297 ng ml(-1) (Cuprophan) and 790 ng ml(-1) (low-flux polysulphone). Equivalent values for C5a(des Arg) were 6.12 (SMC), 2.98 (cellulose acetate), 11.03 (Cuprophan) and 1.33 ng ml(-1) (low-flux polysulphone). C5b-9 values were 385 (SMC), 386 (cellulose acetate), 177 (Cuprophan) and 185 ng ml(-1) (low-flux polysulphone). For each of the complement components the differences between the membranes were significant [P = 0.0009 (C3a(des Arg)), P = 0.0001 (c5a(des Arg) and C5b-9)]. The levels of C5b-9 generated during dialysis also showed a significant positive correlation compared to C5a for all membranes considered as a single group (Pearson's correlation coefficient = 0.870, P = 0.0001). It is concluded that the modification of the cellobiosic unit is a promising approach to improve the biocompatibility profile of cellulose-based membranes. The two different methods of modification lead to similar improvements in biocompatibility compared with unmodified cellulose, but as yet do not match that of low-flux polysulphone.

摘要

肾脏替代治疗主要依赖于使用纤维素基膜。这类膜的生物相容性不如由合成聚合物制成的膜。合成改性纤维素(SMC)是一种新型的低通量血液透析膜,其中的羟基已被苄基取代。通过白细胞和血小板计数的变化以及补体成分(C3a、C5a和C5b - 9)的激活来表征的生物相容性,已在体内进行了研究,并与同一组患者中醋酸纤维素、未改性纤维素(铜仿膜)和低通量聚砜(费森尤斯聚砜)的生物相容性进行了比较。对于SMC,15分钟时白细胞计数降至预处理水平的65.6%,醋酸纤维素为63.8%,低通量聚砜为79.6%,铜仿膜为28.1%,此后恢复到预处理水平。两种改性纤维素膜均优于未改性纤维素(P = 0.001);改性纤维素膜之间的差异无统计学意义。所有三种纤维素基膜引起的变化均超过低通量聚砜(P = 0.001)。与中性粒细胞减少相关的是血小板计数降低,但这与膜的类型无关。150分钟内C3a(去精氨酸)的平均时间平均浓度分别为1168 ng/ml(SMC)、1030 ng/ml(醋酸纤维素)、1297 ng/ml(铜仿膜)和790 ng/ml(低通量聚砜)。C5a(去精氨酸)的等效值分别为6.12(SMC)、2.98(醋酸纤维素)、11.03(铜仿膜)和1.33 ng/ml(低通量聚砜)。C5b - 9的值分别为385(SMC)、386(醋酸纤维素)、177(铜仿膜)和185 ng/ml(低通量聚砜)。对于每种补体成分,膜之间的差异均具有显著性[P = 0.0009(C3a(去精氨酸)),P = 0.0001(C5a(去精氨酸)和C5b - 9)]。将所有膜视为一个整体时,透析过程中产生的C5b - 9水平与C5a也显示出显著的正相关(皮尔逊相关系数 = 0.870,P = 0.0001)。得出的结论是,对纤维二糖单元进行改性是改善纤维素基膜生物相容性的一种有前景的方法。与未改性纤维素相比,两种不同的改性方法在生物相容性方面带来了相似的改善,但尚未达到低通量聚砜的水平。

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