自抗凝透析器的制备及动物透析性能研究

Preparation of self-anticoagulant dialyzer and study on animal dialysis performance

血液透析是治疗肾脏及血液疾病的主要治疗手段,目前临床应用的透析器的核心材料主要是聚砜或聚醚砜透析膜,在透析过程中需要注射低分子肝素钠等抗凝剂,而长期高频的肝素注射会引起出血风险以及多种透析综合症,因此无肝素或减量肝素透析是临床上急需的透析技术.分别发展了界面溶胀交联、疏水吸附以及界面植入凝胶策略制备了3种自抗凝聚砜透析器,分别对中空纤维膜表面形貌及亲水性、血液相容性(活化部分凝血酶时间和凝血酶时间、蛋白黏附、溶血率、补体激活)进行了表征,通过动物透析实验评价了自抗凝透析器的毒素清除率.3种改性透析器血液相容性都得到了明显提高,凝血时间延长,蛋白黏附减少,溶血降低,补体激活也得到了有效抑制.界面溶胀交联法制备的透析器毒素清除率略有下降,其余两种方法制备的透析器毒素清除率相对于原膜有明显提高.分别介绍了每种改性方法的优点以及存在的不足,最终制备了具有良好临床应用前景的自抗凝透析器.

Hemodialysis is the main treatment method for the treatment of kidney and blood diseases.The majority of material in clinical used is polysulfone or polyethersulfone.During the dialysis process,low-molecular-weight heparin sodium and other anticoagulants are indispensable.However,high-frequency heparin injection can cause bleeding risk and various dialysis syndromes,so heparin-free or reduced-heparin dialysis is an urgently needed dialysis technique.Herein,we developed interface swelling and cross-linking,hydrophobic adsorption,and interface implantation gel three strategies to prepare self-anticoagulant dialyzers,then the surface morphology,hydrophilicity and blood compatibility(activated partial clotting enzyme time and thrombin time,protein adhesion,hemolysis rate,complement activation)of as-prepared dialyzers were characterized respectively.And animal dialysis experiments were performed to verify changes in toxin clearance by the modified dialyzer.The blood compatibility of the three modified dialyzers was significantly improved,clotting time was dramatically prolonged,protein adhesion and hemolysis were obviously decreased and complement activation was effectively inhibited.The clearance rate of the dialyzer toxin prepared by the interfacial swelling and cross-linking method decreased slightly,while the clearance rate of the dialyzer toxin prepared by the other two methods significantly improved compared with the original membrane.The advantages and disadvantages of each modification method are introduced separately,and a self-anticoagulant dialyzer with good clinical application prospect is finally prepared.