CN117138126B - 定向清除炎症因子il-6的过滤材料及过滤柱 - Google Patents
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Abstract
本发明公开一种定向清除炎症因子IL‑6的过滤材料，所述过滤材料包括纤维素基纤维条，以及通过环氧树脂固化结合在纤维素基纤维条上的IL‑6R。与现有技术相比，装填本发明过滤材料的过滤柱在血液净化时可通过过滤材料上结合的IL‑6R与血液中的炎症因子IL‑6结合，达到快速、定向清除IL‑6的效果。
Description
技术领域
本发明属于医用材料领域，具体涉及一种定向清除炎症因子IL-6的过滤材料。
背景技术
炎症是人体免疫系统的正常反应，但若无法得到有效控制，免疫系统反而攻击健康组织。在炎症早期，主要是促炎细胞因子发挥作用，白细胞介素-6(IL-6)是促炎细胞因子家族的成员之一，其蛋白结构由四个长α-螺旋组成，包含两个GP130结合位点和一个IL-6Rα结合位点。IL6在炎症部位产生，在急性期反应中起着关键作用。在急性炎症初期，IL-6介导急性期反应。当急性炎症反应回落时，IL-6作为促炎细胞因子的活性持续存在时，便使急性炎症转变成慢性炎症。但是，在急性炎症中，若过度产生IL-6，则会产生细胞因子风暴，从而加重了疾病的后果。在慢性炎症中，IL-6对机体具有损害作用。IL-6通过持续分泌MCP-1，加强血管增生和T细胞的抗凋亡功能，这会导致单核细胞在损伤部位聚集。与此同时，血清中IL-6的水平增加，为慢性炎症增生的提供条件。类风湿关节炎(RA)患者关节内滑膜细胞的浆细胞增多和增生是慢性炎症增生的典型例子。所以在患者发生炎症反应时，当炎症因子IL-6在不同时期患者的体内含量异常时，这时对炎性因子IL-6的定向清除十分有必要。
脓毒症是由菌血症或其他感染引发的严重全身反应。脓毒症起病急，进展迅速，病死率已经超过心肌梗死，成为ICU病房内非心脏病人死亡的主要原因。有文献报道，IL-6可能是发热患者死亡的早期预测指标，因此，对患者体内IL-6因子的升高，需要尽早监测或清除，预防脓毒症的发生。
发明内容
本发明的目的在于提供一种定向清除炎症因子IL-6的过滤材料，可在血液净化时对炎症因子IL-6进行快速定向清除。
本发明为实现上述目的所采用的技术方案如下：
定向清除炎症因子IL-6的过滤材料，其特点在于：所述过滤材料包括纤维素基纤维条，以及通过环氧树脂固化结合在纤维素基纤维条上的IL-6R。
优选地，所述纤维素基纤维条的纤维直径为30～100微米，长度10～20cm。
优选地，所述纤维素基纤维条由中空纤维素基纤维组成。
采用中空纤维素基纤维有利于提高过滤材料与血液的接触面积，增强净化效果。
上述定向清除炎症因子IL-6的过滤材料的制备方法，包括：
(1)将邻苯二胺和丙烯酸混合反应，得到环氧固化剂；
(2)先将双酚A型环氧树脂、环氧固化剂、IL-6R混合均匀，再将纤维素基纤维条放入混合物中，浸润均匀后取出，使混合物均匀的挂在纤维素基纤维条上，待固化后，即得到所述的过滤材料。
采用邻苯二胺和丙烯酸的反应产物作为环氧树脂的固化剂，可以使环氧树脂在室温下实现固化，避免高温固化对IL-6R活性的影响，同时能大大缩短环氧树脂室温固化的时间，提高生产效率。
优选地，邻苯二胺和丙烯酸的质量比为2:1。
更优选地，邻苯二胺和丙烯酸在室温下混合反应50分钟。
优选地，步骤(2)中，环氧固化剂与双酚A型环氧树脂的体积用量比为8:10。
优选地，步骤(2)中，每100ml的双酚A型环氧树脂，加入5～20mg的IL-6R。
优选地，步骤(2)中，在室温下进行固化，时间1～3小时。
一种定向清除炎症因子IL-6的过滤柱，包括柱体和装填在柱体内的过滤材料，其特点在于：所述过滤材料为如上所述定向清除炎症因子IL-6的过滤材料。
有益效果：
1、与现有技术相比，本发明的过滤材料在血液净化时其上结合的IL-6受体(IL-6R)与血液中的炎症因子IL-6结合，从而能快速、定向清除IL-6。
2、本发明IL-6R通过化学共价键与环氧树脂结合，从而提高其与纤维素基纤维条结合牢固性，防止其在血液净化时发生脱落。
具体实施方式
以下结合实施例对本发明的技术方案做进一步详细说明。
使用的材料(均为市售商品)：环氧树脂E-51，丙烯酸，邻苯二胺，纤维素基纤维条(由中空纤维组成的集束，中空纤维的直径为50μm，长约15cm)，IL-6受体(mIL-6R，膜结合型)
制备方法：
1.将邻苯二胺和丙烯酸按质量比为2:1在室温下(25℃)混合反应50min，得到环氧固化剂OPD-HAA。
2.取环氧树脂E-51(100ml)与固化剂OPD-HAA(80ml)混合反应20min，使环氧基团在OPD-HAA作用下开环生成-OH键。
3.然后加入mIL-6R干粉10mg，混合均匀，得到混合物。
4.接着将纤维素基纤维条(500根，约300g)放入步骤3得到的混合物中，浸润均匀后取出，使混合物均匀的挂在纤维条上(滴落的混合物可回收再利用)，室温固化2h。开环的环氧树脂与mIL-6R中的羧基发生脱水缩合，从而使mIL-6R牢固的固定在纤维条上。
5.纤维条固化后装在过滤柱中，对其进行灭菌(25kGy)。
6.过滤柱采用一次性使用血液灌注器，将灭菌后的纤维条装柱，对处于风湿病急性期病人的血浆进行过滤清除处理。血浆中炎症因子IL-6清除前后的含量如下表所示：
| 实验一 | 实验二 | 实验三 | |
| 清除前 | 183pg/ml | 172pg/ml | 102pg/ml |
| 清除后 | 70pg/ml | 49pg/ml | 46pg/ml |
可以看出，过滤材料对IL-6的清除率可达到55％以上。
最后应说明的是：以上所述仅为本发明的优选实施例而已，并不用于限制本发明，尽管参照前述实施例对本发明进行了详细的说明，对于本领域的技术人员来说，其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (8)
1.定向清除炎症因子IL-6的过滤材料，其特征在于：所述过滤材料包括纤维素基纤维条，以及通过环氧树脂固化结合在纤维素基纤维条上的IL-6R；所述纤维素基纤维条的纤维直径为30~100微米，长度10~20cm。
2.根据权利要求1所述定向清除炎症因子IL-6的过滤材料，其特征在于：所述纤维素基纤维条由中空纤维素基纤维组成。
3.权利要求1-2任一所述定向清除炎症因子IL-6的过滤材料的制备方法，包括：
（1）将邻苯二胺和丙烯酸混合反应，得到环氧固化剂；
（2）先将双酚A型环氧树脂、环氧固化剂、IL-6R混合均匀，再将纤维素基纤维条放入混合物中，浸润均匀后取出，使混合物均匀的挂在纤维素基纤维条上，待固化后，即得到所述的过滤材料。
4.根据权利要求3所述的制备方法，其特征在于：邻苯二胺和丙烯酸的质量比为2:1；邻苯二胺和丙烯酸在室温下混合反应50分钟。
5.根据权利要求3所述的制备方法，其特征在于：步骤（2）中，环氧固化剂与双酚A型环氧树脂的体积用量比为8:10。
6. 根据权利要求3所述的制备方法，其特征在于：步骤（2）中，每100ml的双酚A型环氧树脂，加入5~20mg 的IL-6R。
7.根据权利要求3所述的制备方法，其特征在于：步骤（2）中，在室温下进行固化，时间1~3小时。
8.一种定向清除炎症因子IL-6的过滤柱，包括柱体和装填在柱体内的过滤材料，其特征在于：所述过滤材料为如权利要求1-2任一所述定向清除炎症因子IL-6的过滤材料。
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| KR101151139B1 (ko) * | 2004-04-21 | 2012-06-01 | 도레이 카부시키가이샤 | 의료용 필터재 및 그것을 사용한 체외 순환 컬럼과 혈액필터 |
| CA2612195A1 (en) * | 2005-07-01 | 2007-01-11 | Cinvention Ag | Medical devices comprising a reticulated composite material |
| WO2016105595A1 (en) * | 2014-12-23 | 2016-06-30 | Dow Global Technologies Llc | Treated porous material |
| MX2021002422A (es) * | 2018-08-29 | 2021-07-15 | Regeneron Pharma | Métodos y composiciones para el tratamiento de sujetos que padecen artritis reumatoide. |
| EP3959240A1 (en) * | 2019-04-24 | 2022-03-02 | Sanofi Biotechnology | Methods of diagnosis and treatment of rheumatoid arthritis |
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| WO2015084951A1 (en) * | 2013-12-04 | 2015-06-11 | Cornell University | Ceramic-polymer hybrid nanostructures, methods for producing and applications thereof |
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