CN105749886A - 血液灌流器医用高分子微球吸附剂及其制备方法 - Google Patents

血液灌流器医用高分子微球吸附剂及其制备方法 Download PDF

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CN105749886A
CN105749886A CN201610218328.XA CN201610218328A CN105749886A CN 105749886 A CN105749886 A CN 105749886A CN 201610218328 A CN201610218328 A CN 201610218328A CN 105749886 A CN105749886 A CN 105749886A
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adsorbing agent
microsphere
microsphere adsorbing
perfusion device
high polymer
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任力
王迎军
刘卅
王琳
郑建
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South China University of Technology SCUT
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Priority to PCT/CN2017/079646 priority patent/WO2017174016A1/zh
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Abstract

本发明公开了血液灌流器医用高分子微球吸附剂及其制备方法；本发明采用不同孔径及比表面积苯乙烯‐二乙烯苯微球的级配，并通过对其进行医用纯化处理和生物活性可控接枝技术处理，制备出微球吸附剂。微球吸附剂中1‐10μm、10‐100μm和100‐500μm尺寸范围的微球体积比为1:(1‐10):(1‐20)，微球中残留单体含量O.D190‐400nm≤0.03。本发明所制备的血液灌流器医用高分子微球吸附剂不但可以吸附血液中有害的小分子，还可以有效地吸附血液中有害的中、大分子，满足临床应用需求。

Description

血液灌流器医用高分子微球吸附剂及其制备方法
技术领域
本发明涉及血液净化技术领域，具体涉及一种新型血液灌流器医用高分子微球吸附剂及其制备方法。
背景技术
血液净化技术为二十世纪后期在治疗慢性肾功能衰竭的基础上发展起来的一种新型医疗技术。目前全世界需要进行血液净化的患者约有2000万人，而我国约有300万人。由于维持血液净化治疗费用昂贵，我国目前只有10％的患者能够接受治疗。因此，该项技术的研发具有巨大的潜力。
聚苯乙烯‐二乙烯基苯微球作为血液灌流器中最常用的医用高分子微球吸附剂，可以吸附血液中一定的中分子β2微球蛋白。但是目前用于血液灌流器中的苯乙烯‐二乙烯苯微球吸附剂仍具有以下不足。首先，未对孔径进行级配设计，这就导致了其主要吸附物质为肌酐、戊巴比妥等透析易清除的小分子物质，而对中大分子物质很难清除。其次，目前国内在活化中性大孔苯乙烯‐二乙烯苯微球时，易导致强烈刺激性化学物质氯甲醚和硝基苯的残留，对患者的健康存在极大的安全隐患。再次，吸附剂的血液相容性差，与血液直接接触会破坏红细胞、白细胞和血小板等。因此，如何改进医用高分子微球吸附剂是血液净化技术一个重要的研究方向。
发明内容
本发明的目的是针对目前血液灌流器存在的问题，提供一种可以更加高效去除血液中有害物质的医用高分子微球吸附剂，在有效去除血液中小分子有害物质的同时，也可以去除中、大分子有害物质。
本发明的目的通过以下措施实现：
一种血液灌流器医用高分子微球吸附剂，由直径分别为1‐10μm、10‐100μm和100‐500μm三种苯乙烯‐二乙烯苯高分子微球按体积比1:(1‐10):(1‐20)组成；微球吸附剂表面接枝有乙烯基吡咯烷酮和/或2‐甲基丙烯酰氧基乙基磷酰胆碱；微球吸附剂中残留单体含量O.D190‐400nm≤0.03。
优选地，所述微球吸附剂表面积为400m2/g‐1800m2/g。
所述苯乙烯‐二乙烯苯高分子微球的原料符合FDA规定，二乙烯苯质量含量大于79％，所述苯乙烯‐二乙烯苯高分子微球能够承受300‐450g重压，且具有2.2‐3.1mmol/g悬挂双键含量。
所述血液灌流器医用高分子微球吸附剂的制备方法，包括步骤如下：
1)微球吸附剂孔径及比表面积的级配：将苯乙烯‐二乙烯苯高分子微球按照直径分别为1‐10μm、10‐100μm和100‐500μm三种尺寸进行分离；按体积比1:(1‐10):(1‐20)将三种尺寸范围内的微球进行混合；
2)微球吸附剂的医用纯化处理：对步骤1)所得为求吸附剂依次利用盐酸、氨水和乙醇水进行清洗，然后对微球吸附剂进行水洗联合处理和梯度淋洗；
3)利用生物活性可控接枝技术在微球吸附剂表面接枝生物活性配基：将步骤2)纯化处理后的微球吸附剂浸于生物活性配基溶液1‐24h；所述生物活性配基为聚乙烯吡咯烷酮和/或2‐甲基丙烯酰氧基乙基磷酰胆碱；然后将微球取出后置于紫外光下进行接枝，其中光的强度为50uw/cm2‐150uw/cm2，接枝时间1‐4h；
4)微球吸附剂的后处理：接枝后的微球取出后，利用缓冲溶液浸泡1‐3h，并利用去离子水清洗；冷冻干燥，得血液灌流器医用高分子微球吸附剂。
优选地，所述的盐酸质量浓度为1％‐5％；氨水质量浓度为5％‐10％；乙醇水质量浓度为10‐20％。
优选地，所述的生物活性配基溶液质量浓度为1％‐10％。
优选地，所述的紫外光距离待处理溶液1m距离。
优选地，所述的冷冻干燥在冷冻干燥机中进行，冷冻干燥的时间为12‐24h。
优选地，所述的缓冲溶液为PBS。
优选地，所述的去离子水清洗的次数为3‐10次。
聚乙烯吡咯烷酮(PVP)是一种水溶性高分子化合物，具有高亲水性、优异的生物相容性和生理惰性，不参与人体新陈代谢，对皮肤、粘膜、眼等不形成任何刺激，广泛用于医药、食品、化妆品等于人类健康密切相关的领域。2‐甲基丙烯酰氧基乙基磷酰胆碱(MPC)是一种含有磷酰胆碱(PC)基团的单体，具有双离子性，一定条件下其聚合物可以形成类似生物膜的双分子层。另外，MPC聚合膜可以有效抑制蛋白吸附和血小板粘附，能有效抑制血凝块的形成，具有良好的血液相容性。因此，将这两种化合物用于修饰高分子微球吸附剂具有广阔的应用前景。
本发明与现有技术相比有如下优点：
1.医用高分子微球吸附剂的孔径及比表面积的级配和筛选技术采用FDA认可厂商生产的高分子微球，筛选具有一定孔径分布及一定力学强度和反应活性的微球，确保全血能够顺利通过灌流器而不产生太大阻力，并确保微球在压力下不被破坏。利用具有不同孔径的高分子微球进行级配，使其微球孔径分布符合不同分子大小毒素分离要求，实现对不同尺寸目标毒素的有效分离。
2.采用酸洗、碱洗、醇洗及水洗联合处理工艺和梯度淋洗工艺，对经过级配和筛选的高分子微球吸附剂进行纯化处理，有效去除残存杂质，使其达到血液净化的要求，降低使用风险，提高产品使用的安全可靠性。
3.利用生物活性可控接枝技术将生物活性配基接枝到高分子微球吸附剂上，在高分子微球表面引入具有良好血液相容性的生物活性分子(如PVP、MPC等)，从而提高微球的血液相容性，减少红细胞等细胞变形，避免产生微粒引发的栓塞。提升灌流器生物相容性和血液相容性的同时利用生物活性分子上的电荷与目标毒素之间的相互吸引作用，提高对目标毒素的清除率。
附图说明
图1为实施例1微球接枝NVP和MPC前后红外测试图。
具体实施方式
为更好地理解本发明，下面结合附图和实施例对本发明作进一步的说明，但本发明的实施方式不限如此。
实施例1
选用符合FDA规定的、二乙烯苯质量含量大于79％的苯乙烯‐二乙烯苯高分子微球苯乙烯‐二乙烯苯高分子微球作为原料，该微球能够承受300‐450g重压且具有2.2‐3.1mmol/g悬挂双键含量。
步骤一：微球吸附剂孔径及比表面积的级配
(1)将1‐10μm、10‐100μm和100‐500μm三种尺寸范围的微球按照体积比1:8:10混合，混合后比表面积约为951.8m2/g
步骤二：微球吸附剂的医用纯化处理：依次进行如下清洗
(1)对微球吸附剂利用质量浓度为2％的盐酸进行清洗2min；
(2)对微球吸附剂利用质量浓度为5％的氨水进行清洗9min；
(3)对微球吸附剂利用质量浓度为20％的乙醇进行清洗2min；
(4)对微球吸附剂进行水洗联合处理和梯度淋洗。
经检测，清洗后微球O.D190‐400nm＝0.03
步骤三：利用生物活性可控接枝技术在微球吸附剂表面接枝生物活性配基
(1)将微球浸于质量浓度为6％的乙烯基吡咯烷酮(NVP)和质量浓度为7％2‐甲基丙烯酰氧基乙基磷酰胆碱(MPC)生物活性配基溶液中16h；
NVP分子结构式为：
MPC分子结构式为：
(2)将微球取出后置于紫外光下进行接枝，其中光的强度为80uw/cm2(1m距离处)，接枝时间3h；
步骤四：微球吸附剂的后处理
(1)接枝后的微球取出后，利用PBS缓冲溶液浸泡3h，并利用去离子水清洗10次；
(2)将微球置于冷冻干燥机中，冷冻干燥18h，最后得到新型血液灌流器医用高分子微球吸附剂。
测试结果：微球接枝前后的红外测试结果如图1所示；具体而言，图1是将改性前后的微球样品进行红外光谱测试(使用压片法制备样品)得到的测试结果图；其中，PS‐DVB表示苯乙烯‐二乙烯苯高分子微球；NVP表示乙烯基吡咯烷酮；MPC表示2‐甲基丙烯酰氧基乙基磷酰胆碱。
为了说明微球对血液中毒素的清除效率。通过本实施例改性后微球对小分子毒素肌酐和戊巴比妥钠，中分子毒素维生素B12和β2微球蛋白的清除率如表1所示。
表1微球对毒素的清除率
表1中，肌酐初始浓度35mg/L，戊巴比妥钠初始浓度80mg/L，维生素B12初始浓度25mg/L，β2微球蛋白初始浓度1mg/mL。表1说明本实施例制备的吸附剂不但可以吸附血液中有害的小分子，还可以有效地吸附血液中有害的中、大分子，满足临床应用需求。目前现有市场上的聚苯乙烯‐二乙烯基苯微球应用于血液灌流需要联合血液透析才能实现对小分子及中分子均可有效清除(孙韬.不同血液净化方式对毒素清除及透析充分性的比较[D]:吉林大学；2009.)。本发明制备微球应用于血液灌流，可以单独使用，实现小分子及中分子均可有效清除。
溶血率是溶血率是应用于生物医用的材料在与血液接触时，表征材料对血液中红细胞的破坏程度，通过测定红细胞溶解和血红蛋白游离的程度来表示。微球改性前后的溶血率测试结果表2所示。表2是根据国标GB/T16886.4-2003中规定进行试验，溶血率需要小于5％。
表2微球溶血率测试结果
溶血率(HR)是材料血液相容性非常重要的指标之一，是一项重要的体外粗筛实验。国家对与血液接触的生物医用材料的溶血实验标准是材料标准溶血率(HR)<5％。测试表明本发明制备的材料的溶血率结果与市场上的产品基本类似，达到国家标准。
实施例2
选用符合FDA规定的、二乙烯苯质量含量大于79％的苯乙烯‐二乙烯苯高分子微球苯乙烯‐二乙烯苯高分子微球作为原料，该微球能够承受300‐450g重压且具有2.2‐3.1mmol/g悬挂双键含量。
步骤一：微球吸附剂孔径及比表面积的级配
(1)将1‐10μm、10‐100μm和100‐500μm三种尺寸范围的微球按照体积比1:8:18混合，混合后比表面积约为578.5m2/g
步骤二：微球吸附剂的医用纯化处理
(1)对微球吸附剂利用质量浓度为5％的盐酸进行清洗1min；
(2)对微球吸附剂利用质量浓度为10％的氨水进行清洗8min；
(3)对微球吸附剂利用质量浓度为10％的乙醇进行清洗19min；
(4)对微球吸附剂进行水洗联合处理和梯度淋洗。
清洗后O.D190‐400nm＝0.025。
步骤三：利用生物活性可控接枝技术在微球吸附剂表面接枝生物活性配基
(1)将微球浸于质量浓度为7％的乙烯基吡咯烷酮(NVP)和质量浓度为2％2‐甲基丙烯酰氧基乙基磷酰胆碱(MPC)生物活性配基溶液中12h；
(2)将微球取出后置于紫外光下进行接枝，其中光的强度为100μW/cm2(1m距离处)，接枝时间1h；
步骤四：微球吸附剂的后处理
(1)接枝后的微球取出后，利用PBS缓冲溶液浸泡1h，并利用去离子水清洗8次；
(2)将微球置于冷冻干燥机中，冷冻干燥20h，最后得到新型血液灌流器医用高分子微球吸附剂。
实施例3
选用符合FDA规定的、二乙烯基苯质量含量大于79％的苯乙烯‐二乙烯苯高分子微球，苯乙烯‐二乙烯苯高分子微球作为原料，该微球能够承受300‐450g重压且具有2.2‐3.1mmol/g悬挂双键含量。
步骤一：微球吸附剂孔径及比表面积的级配
(1)将1‐10μm、10‐100μm和100‐500μm三种尺寸范围的微球按照体积比1:5:12混合，混合后比表面积约为732.5m2/g
步骤二：微球吸附剂的医用纯化处理
(1)对微球吸附剂利用质量浓度为1％的盐酸进行清洗10min；
(2)对微球吸附剂利用质量浓度为7％的氨水进行清洗10min；
(3)对微球吸附剂利用质量浓度为12％的乙醇进行清洗20min；
(4)对微球吸附剂进行水洗联合处理和梯度淋洗。
清洗后O.D190‐400nm＝0.01
步骤三：利用生物活性可控接枝技术在微球吸附剂表面接枝生物活性配基
(1)将微球浸质量浓度为于3％的乙烯基吡咯烷酮(NVP)和质量浓度为2％2‐甲基丙烯酰氧基乙基磷酰胆碱(MPC)生物活性配基溶液中24h；
(2)将微球取出后置于紫外光下进行接枝，其中光的强度为150uw/cm2(1m距离处)，接枝时间4h；
步骤四：微球吸附剂的后处理
(1)接枝后的微球取出后，利用PBS缓冲溶液浸泡3h，并利用去离子水清洗5次；
(2)将微球置于冷冻干燥机中，冷冻干燥14h，最后得到新型血液灌流器医用高分子微球吸附剂。
对实施例2和实施例3所得新型血液灌流器医用高分子微球吸附剂对小分子毒素肌酐和戊巴比妥钠，中分子毒素维生素B12和β2微球蛋白的清除效果测试结果如表3所示。
表3

Claims (10)

1.一种血液灌流器医用高分子微球吸附剂，其特征在于：所述微球吸附剂由直径分别为1‐10μm、10‐100μm和100‐500μm三种苯乙烯‐二乙烯苯高分子微球按体积比1:(1‐10):(1‐20)组成；微球吸附剂表面接枝有乙烯基吡咯烷酮和/或2‐甲基丙烯酰氧基乙基磷酰胆碱；微球吸附剂中残留单体含量O.D190‐400nm≤0.03。
2.根据权利要求1所述的血液灌流器医用高分子微球吸附剂，其特征在于：所述微球吸附剂表面积为400m2/g‐1800m2/g。
3.根据权利要求1所述的血液灌流器医用高分子微球吸附剂，其特征在于：所述苯乙烯‐二乙烯苯高分子微球的原料符合FDA规定，二乙烯苯质量含量大于79％，所述苯乙烯‐二乙烯苯高分子微球能够承受300‐450g重压，且具有2.2‐3.1mmol/g悬挂双键含量。
4.权利要求1所述血液灌流器医用高分子微球吸附剂的制备方法，其特征在于包括步骤如下：
1)微球吸附剂孔径及比表面积的级配：将苯乙烯‐二乙烯苯高分子微球按照直径分别为1‐10μm、10‐100μm和100‐500μm三种尺寸进行分离；按体积比1:(1‐10):(1‐20)将三种尺寸范围内的微球进行混合；
2)微球吸附剂的医用纯化处理：对步骤1)所得为求吸附剂依次利用盐酸、氨水和乙醇水进行清洗，然后对微球吸附剂进行水洗联合处理和梯度淋洗；
3)利用生物活性可控接枝技术在微球吸附剂表面接枝生物活性配基：将步骤2)纯化处理后的微球吸附剂浸于生物活性配基溶液1‐24h；所述生物活性配基为聚乙烯吡咯烷酮和/或2‐甲基丙烯酰氧基乙基磷酰胆碱；然后将微球取出后置于紫外光下进行接枝，其中光的强度为50uw/cm2‐150uw/cm2，接枝时间1‐4h；
4)微球吸附剂的后处理：接枝后的微球取出后，利用缓冲溶液浸泡1‐3h，并利用去离子水清洗；冷冻干燥，得血液灌流器医用高分子微球吸附剂。
5.根据权利要求4所述的血液灌流器医用高分子微球吸附剂的制备方法，其特征在于：所述的盐酸质量浓度为1％‐5％；氨水质量浓度为5％‐10％；乙醇水质量浓度为10‐20％。
6.根据权利要求4所述的血液灌流器医用高分子微球吸附剂的制备方法，其特征在于：所述的生物活性配基溶液质量浓度为1％‐10％。
7.根据权利要求4所述的血液灌流器医用高分子微球吸附剂的制备方法，其特征在于：所述的紫外光距离待处理溶液1m距离。
8.根据权利要求4所述的血液灌流器医用高分子微球吸附剂的制备方法，其特征在于：所述的冷冻干燥在冷冻干燥机中进行，冷冻干燥的时间为12‐24h。
9.根据权利要求4所述的血液灌流器医用高分子微球吸附剂的制备方法，其特征在于：所述的缓冲溶液为PBS。
10.根据权利要求4所述的血液灌流器医用高分子微球吸附剂的制备方法，其特征在于：所述的去离子水清洗的次数为3‐10次。
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017174016A1 (zh) * 2016-04-08 2017-10-12 华南理工大学 血液灌流器医用高分子微球吸附剂及其制备方法
CN110327893A (zh) * 2019-06-05 2019-10-15 南京亘闪生物科技有限公司 一种用于胆红素血液净化高分子微球及其制备方法
CN110327894A (zh) * 2019-06-05 2019-10-15 南京亘闪生物科技有限公司 一种高吸附量的血液净化高分子微球及其制备方法
CN110711276A (zh) * 2019-09-06 2020-01-21 武汉瑞法医疗器械有限公司 一种稳定吸附剂吸附性能的保存液

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113372474B (zh) * 2021-06-29 2023-10-20 西安蓝晓科技新材料股份有限公司 一种血液灌流树脂及其制备方法和应用
CN114113394B (zh) * 2021-11-24 2023-12-01 宁波市疾病预防控制中心 用于提取净化百草枯代谢物的磁性微球、制备方法、试剂盒及提取方法
CN114984608B (zh) * 2022-06-13 2024-01-30 天津大学 制备球形反渗透薄膜储存晶体颗粒的方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030027879A1 (en) * 1998-08-28 2003-02-06 Vadim Davankov Hypercrosslinked polymeric material for purification of physiological liquids of organism, and a method of producing the material
US20080119576A1 (en) * 2006-11-20 2008-05-22 Wei-Tai Young Size-selective hemoperfusion polymeric adsorbents
CN102344827A (zh) * 2010-08-05 2012-02-08 中国石油化工股份有限公司 一种催化裂化重油加氢方法
CN102847521A (zh) * 2011-06-28 2013-01-02 于杰 大孔吸附树脂及其应用
CN103533830A (zh) * 2011-01-06 2014-01-22 西托索尔本茨公司 用于从全血和血液制品中移除杂质的聚合物吸附剂
CN105188799A (zh) * 2013-04-01 2015-12-23 西托索尔本茨公司 交联聚合物材料的血液相容性修饰剂

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105749886A (zh) * 2016-04-08 2016-07-13 华南理工大学 血液灌流器医用高分子微球吸附剂及其制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030027879A1 (en) * 1998-08-28 2003-02-06 Vadim Davankov Hypercrosslinked polymeric material for purification of physiological liquids of organism, and a method of producing the material
US20080119576A1 (en) * 2006-11-20 2008-05-22 Wei-Tai Young Size-selective hemoperfusion polymeric adsorbents
CN102344827A (zh) * 2010-08-05 2012-02-08 中国石油化工股份有限公司 一种催化裂化重油加氢方法
CN103533830A (zh) * 2011-01-06 2014-01-22 西托索尔本茨公司 用于从全血和血液制品中移除杂质的聚合物吸附剂
CN102847521A (zh) * 2011-06-28 2013-01-02 于杰 大孔吸附树脂及其应用
CN105188799A (zh) * 2013-04-01 2015-12-23 西托索尔本茨公司 交联聚合物材料的血液相容性修饰剂

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
童伟芳: "聚乙烯基吡咯烷酮可控接枝修饰材料表面及其蛋白吸附", 《中南民族大学硕士学位论文》 *
郑建: "聚乙烯基吡咯烷酮可控接枝修饰材料", 《华南理工大学工程硕士学位论文》 *
黄文强等: "《吸附分离材料》", 31 July 2005, 化学工业出版社 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017174016A1 (zh) * 2016-04-08 2017-10-12 华南理工大学 血液灌流器医用高分子微球吸附剂及其制备方法
US10758889B2 (en) 2016-04-08 2020-09-01 South China University Of Technology Medical macromolecular microsphere adsorbent for a blood perfusion apparatus and a preparation method thereof
CN110327893A (zh) * 2019-06-05 2019-10-15 南京亘闪生物科技有限公司 一种用于胆红素血液净化高分子微球及其制备方法
CN110327894A (zh) * 2019-06-05 2019-10-15 南京亘闪生物科技有限公司 一种高吸附量的血液净化高分子微球及其制备方法
CN110711276A (zh) * 2019-09-06 2020-01-21 武汉瑞法医疗器械有限公司 一种稳定吸附剂吸附性能的保存液
CN110711276B (zh) * 2019-09-06 2022-05-17 武汉瑞法医疗器械有限公司 一种稳定吸附剂吸附性能的保存液

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