自抗凝透析器的制备及动物透析性能研究
作者:柳杨,王辉,刘富
单位: 1. 中国科学院 宁波材料技术与工程研究所,宁波 315201;2.青岛科技大学 高分子科学与工程学院,青岛 266042
关键词: 自抗凝透析器;无肝素透析;界面溶胀;疏水吸附;界面植入
出版年,卷(期):页码: 2020,40(1):84-92

摘要:
 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征,因此无肝素或减量肝素透析是临床上急需的透析技术。我们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三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。三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,蛋白粘附减少,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.
第一作者简介:柳杨(1993-),女,山东青岛人,硕士,从事功能膜分离研究,E-mail: liuyang123@nimte.ac.cn 通信作者:刘富,E-mail:fu.liu@nimte.ac.cn

参考文献:
 [1] 肖月,隋宾艳,赵琨.我国终末期肾病现状及透析技术的应用、费用及支付情况分析[J].中国卫生政策研究,2011,4:29-33
[2] 唐克诚,李谦,王瑞,等.血液透析膜材料的研究进展[J].医疗设备信息, 2007,22:49-51. 
[3] Lipps B Stewart R, Perkims H. The hollow fiber artificial kidney[J]. Trans Am Soc Artif Interm Org, 1969,13:200-206.
[4] Jing D, Katsuji S, Zheng C. The anticonvulsants lamotrigine, riluzole, and valproate differentially regulate AMPA receptor membrane lacalition: relationship to clinical effects in mood disorders[J]. Neuropsychopharmacology, 2007,32:793-802.
[5] 高爱林,刘富,薛立新.生物基聚乳酸微孔膜的制备及透析性能[J].膜科学与技术,2013,33(4):29-34.
[6] 刘耀东, 黄鑫, 王伟平.聚砜中空纤维膜式人工肺的等离子体改性研究[J].膜科学与技术,2015, 35(4):35-39.
[7] 俞学敏, 朱丽静, 高爱林.血液透析膜的制备改性及组件设计[J].膜科学与技术, 2015, 35(4):110-122.
[8] 王丹丹, 杨宁, 贾雪梦.抗氧化聚砜血液透析膜的构建与性能研究[J].膜科学与技术, 2018, 38;No.189(02):26-32.
[9] Folwaczny C, Wiebecke C, Loeschke K, Unfractioned heparin in the therapy of patients with highly active inflammatory bowel disease[J], The American journal of gastroenterology, 1999,94:1551-1555.
[10] Yue W W, Li H J, Xiang T, Qin H, Sun S D, Zhao C S. Grafting of zwitterion from polysulfone membrane via surface-initiated ATRP with enhanced antifouling property and biocompatibility[J]. J. Membr. Sci, 2013,446:79-91. 
[11] Zhao Y F, Zhu L P, Yi Z, et al. Improving the hydrophilicity and fouling-resistance of polysulfone ultrafiltration membranes via surface zwitterionicalization mediated by polysulfone-based triblock copolymer additive[J]. J. Membr. Sci, 2013,440:40-47.
[12] Wang H, Hou W, Liu F, et al. Preparation and evaluation of a self-anticlotting dialyzer via an interface crosslinking approach[J], J. Membr. Sci, 2018,563:115-125.
[13] Gao A L, Liu F, Xue L X, Preparation and evaluation of heparin-immobilized poly (lactic acid) (PLA) membrane for hemodialysis[J], J. Membr. Sci, 2014,452:390-399.
[14] Ji H, Xu H, Jin L, et al. Surface engineering of low-fouling and hemocompatible polyethersulfone membranes via in-situ ring-opening reaction[J], J. Membr. Sci, 2019,581:373-382.
[15] He M, Cui X, Jiang H, et al. Super-anticoagulant heparin-mimicking hydrogel thin film attached substrate surfaces to improve hemocompatibility[J], Macromol. Biosci. 2017,17:1600281.
[16] Tamada Y, Murata M, Hayashi T, et al. Anticoagulant mechanism of sulfonated polyisoprenes[J], Biomaterials, 2002, 23(5): 1375-1382.
[17] Park H D, Lee W K, Ooya T, et al. Anticoagulant activity of sulfonated polyrotaxanes as blood-compatible materials[J], J. Biomed. Mater. Res, 2002, 60(1): 186-190.
[18] Strnad S, Velkova N, Saake B, et al. Influence of sulfated arabino- and glucuronoxylans charging-behavior regarding antithrombotic properties[J], React. Funct. Polym, 2013, 73(12): 1639-1645.
[19] Tang M, Xue J, Yan K, et al. Heparin-like surface modification of polyethersulfone membrane and its biocompatibility[J], J. Colloid Interface Sci, 2012,386:428-440.
[20] Zhou H, Cheng C, Qin H, et al. Self-assembled 3D biocompatible and bioactive layer at the macro-interface via graphene-based supermolecules[J], Polym. Chem, 2014, 5(11): 3563-3575
[21] Qin H, Sun C, He C, et al. High efficient protocol for the modification of polyethersulfone membranes with anticoagulant and antifouling properties via in situ cross-linked copolymerization[J], J. Membr. Sci, 2014, 468(20): 172-183
[22] Nie S, Tang M, Cheng C, et al. Biologically inspired membrane design with a heparin-like interface: prolonged blood coagulation, inhibited complement activation, and bio-artificial liver related cell proliferation[J], Biomaterials Science, 2014, 2(1): 98-109.

服务与反馈:
文章下载】【加入收藏

《膜科学与技术》编辑部 地址:北京市朝阳区北三环东路19号蓝星大厦 邮政编码:100029 电话:010-64426130/64433466 传真:010-80485372邮箱:mkxyjs@163.com

京公网安备11011302000819号