CN102905522A - 用于从红细胞中除去氧的氧消耗装置和方法 - Google Patents

用于从红细胞中除去氧的氧消耗装置和方法 Download PDF

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CN102905522A
CN102905522A CN2010800564451A CN201080056445A CN102905522A CN 102905522 A CN102905522 A CN 102905522A CN 2010800564451 A CN2010800564451 A CN 2010800564451A CN 201080056445 A CN201080056445 A CN 201080056445A CN 102905522 A CN102905522 A CN 102905522A
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威廉·J·费德施皮尔
吉田达郎
保罗·J·韦尔尼奇
布赖恩·J·弗兰考斯基
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Abstract

氧消耗装置。所述装置具有：盒；多个中空纤维，其在所述盒中从其入口延伸至其出口；一定量的氧清除剂，其被装入所述盒中并且处于所述多个中空纤维之间并与其相接触。所述中空纤维适于接收并且输送红细胞。还有用于从红细胞中除去氧的氧消耗装置和方法的另一种实施方案。

Description

用于从红细胞中除去氧的氧消耗装置和方法
发明背景
1.技术领域
本发明涉及用于从红细胞中消耗氧以提高贮藏寿命的装置。本发明涉及用于从红细胞中消耗氧的方法。
2.背景技术
充足的血液供应及其贮藏是全世界每个大型医院和健康组织所面临的问题。所贮藏的血液供应量经常远低于对它的需要。危机时期(例如，自然灾难、战争等)尤其如此，此时血液供应通常处于耗尽的危险中。在像这样的危急时期经常听到捐赠更多新鲜血液的呼声。然而，不幸的是，即便没有危难时期，也必须时常监控和补充血液供应以及贮藏中的血液供应，因为贮藏的血液不能长期保持其活力。
贮藏的血液发生稳定的变质，这部分由血红蛋白的氧化和降解以及腺苷三磷酸(ATP)和2-3，二磷酸甘油酸(DPG)的消耗所引起。氧导致红细胞(RBC)所携带的血红蛋白(Hb)转变为met-Hb，其分解产生有毒的产物，例如血色质(hemichrome)、氯化高铁血红素(hemin)和游离的Fe3+。这些产物与氧一起催化羟自由基(OH.cndot.)的形成，并且OH.cndot.和met-Hb的分解产物都损害红细胞的脂膜、膜骨架和细胞内含物。正因为如此，认为贮藏的血液6周后不能使用，这是通过红细胞相对无能力在接受输血者的循环中存活而确定的。DPG的消耗阻止充足的氧运输到组织，因而在施用之后立即降低输血的效果(8～48小时后，接受者中DPG的水平再次恢复)。此外，这些有害的作用还导致使用失效日期之前(但可能已超过两周)的贮藏血液进行的输血治疗的整体效果降低并且副作用升高。
因此，需要在长期贮藏之前能够在红细胞中消耗氧水平，使贮藏血液不发生由氧和血红蛋白的相互作用而导致的有害作用。
发明概述
因此，本公开内容提供能够从红细胞中除去氧的一次性装置。
本公开内容提供氧消耗装置。所述装置具有：盒；多个中空纤维，其在所述盒中从其入口延伸至其出口；一定量的氧清除剂，其被装入所述盒中并且处于所述多个中空纤维之间并与其相接触。所述中空纤维适于接收和输送红细胞。
本公开内容提供氧消耗装置。所述装置具有固体材料的容器(其具有适于接收和排出冲刷气体的进气口和排气口)以及多个中空纤维(其在所述容器中从其入口延伸至其出口)。所述中空纤维适于接收和输送红细胞。
本公开内容提供用于从红细胞中除去氧的方法。所述方法具有使红细胞通过氧装置的步骤。所述装置具有：盒；多个中空纤维，其在所述盒中从其入口延伸至其出口；以及一定量的氧清除剂，其被装入所述盒中并且处于所述多个中空纤维之间并与其相接触。所述中空纤维适于接收和输送红细胞。
本公开内容提供用于从红细胞中除去氧的方法。所述方法具有使红细胞通过氧装置的步骤。所述装置具有：固体材料的容器，其具有适于接收和排出冲刷气体的进气口和排气口；以及多个中空纤维薄膜，其在所述容器中从其入口延伸至其出口。所述中空纤维适于接收和输送红细胞。
通过下文中参照附图的详细描述，本公开内容及其特征和优势将变得更加显而易见。
附图简述
图1示出本发明的贮藏前氧消耗装置。
图2a至2c示出消耗装置的实施方案，所述消耗装置通过在组件内中空纤维周围用冲刷惰性气体进行冲刷而在贮藏前从红细胞中消耗氧。
图3a至3c示出消耗装置的另一个实施方案，所述消耗装置在贮藏前从红细胞中消耗氧。
图4a至4c示出消耗装置的另一个实施方案，所述消耗装置在贮藏前从红细胞中消耗氧，其中氧被中空纤维周围圆筒芯中的清除剂材料所清除。
图5a至5c示出消耗装置的另一个实施方案，所述消耗装置从红细胞中消耗氧，其中氧被中空纤维之圆筒周围的清除剂材料所清除。
图6示出用于图2a至2c、图3a至3c、图4a至4c以及图5a至5c的消耗装置的每分钟RBC悬浮液流量对氧分压的图。
具体实施方式
参照图2，氧消耗装置(oxygen depletion device，ODD)101含有氧吸附剂110。ODD 101是一次性的盒(cartridge)105，其含有氧吸附剂110和一系列中空纤维115。氧吸附剂110是无毒的无机和/或有机盐和对氧具有高反应性的亚铁或其他材料的混合物。氧吸附剂110由这样的颗粒制成，所述颗粒具有显著地吸收O2的能力(超过5ml O2/g)，并且可使盒105内部维持低于0.01％，这相当于少于0.08mmHg的PO2。氧吸收剂110或是游离的或是包含在氧可渗透性包膜中。本公开内容的ODD 101能从一个单位的血液中消耗约100mL氧。
RBC通过中空多孔纤维115。多孔纤维具有高的氧渗透率。多孔纤维的合适材料包括聚烯烃、特氟龙(Teflon)、聚酯、PVDF、聚砜和其他疏水聚合物以及无机材料(陶瓷)。氧消耗发生在当RBC通过膜115时。ODD提供具有大的表面积的简单结构以除去氧并且维持血液以恒定流量从其中通过。氧的消耗或除去通过氧吸附剂110中的亚铁离子与周围的氧不可逆反应形成氧化铁而完成。ODD 101用于除氧时无需振荡并且可很容易地制造成在必要时承受作为血液收集***之一部分的离心。
参照图2a至2c和图3a至3c，公开了冲刷消耗装置的实例。所述消耗装置通过供应合适组成的冲刷气体而发挥消耗O2的功能。适于消耗装置的气体包括例如Ar、He、CO2、N2。
图4a至4c和图5a至5c也公开了清除消耗装置。通过使用清除剂或吸附剂(而不是使用外部气体)进行消耗。然而，在这两种类型的消耗装置中，在血液贮藏袋中贮藏之前，氧消耗分别有效地升高DPG和ATP。
参照图2a至2c，其中示出消耗装置20。消耗装置20包含多个纤维25，数量为约5000，红细胞从其中流过。多个纤维25被塑料圆筒30环绕。塑料圆筒30包含进气口35和排气口40，通过它们供应冲刷气体(如上文提及的冲刷气体)或其组合以从血液中除去氧。如下表1中显示消耗装置20的规格。
表1
Figure BDA00001756724100041
参照图3a至3c，其中示出消耗装置45。像图2a至2c的装置20一样，消耗装置45包含多个纤维50，数量为约5000，红细胞从其中流过。多个纤维50被塑料圆筒55环绕。塑料圆筒55包含进气口60和排气口65，通过它们供应气体(如上文提及的气体)或其组合以从血液中除去氧。如下表2中显示消耗装置45的规格。装置45之有效消耗表面积是装置20的两倍，因为装置45的长度是装置20的两倍。
表2
Figure BDA00001756724100042
图4a至4c公开了消耗装置70，其具有芯75，所述芯75含有用于O2的清除材料。芯75包装在气体可渗透性薄膜中，所述薄膜具有很低的液体渗透性。中空纤维80绕在芯75，并且塑料圆筒82有并且包封中空纤维80。在这个具体的实施方案中，有效消耗表面积是约0.8796m2，如以下表3所示。
表3
Figure BDA00001756724100051
图5a至5c公开了消耗装置85，其含有纤维束87，所述纤维束87包封在气体可渗透性薄膜中，所述薄膜具有很低的液体渗透性。纤维束87被用于O2的清除剂材料89所包围。纤维束87和清除剂材料89包含在塑料圆筒90中。如以下表4所示，有效消耗表面积是约0.8796m2。
表4
Figure BDA00001756724100052
图6是冲刷消耗装置20和45以及清除消耗装置70和85之性能的图。使用以下条件用图6的数据作图：红细胞比容，62％(合并3个单位的pRBC)，以及21℃在多种头高(head height)以产生不同的流速。分别为装置79和装置85添加5％和12％w/w的水蒸汽以活化氧清除剂(Multisorb Technologies，Buffalo，NY)。以流速(g RBC悬液/分钟)对pO2(mmHg)对数据进行作图。
在本文所公开的氧消耗装置中，所述中空纤维可以任何适当的构造装入所述盒中，例如线性的或纵向的、螺旋的或者线圈样的，只要它们可接收并输送红细胞即可。
图6显示使用装置45和85所达到的最低氧饱和度。装置45展示出沿纤维50之长度暴露于气体的更大有效表面积。装置85还具有暴露于清除材料的长的表面积。装置85具有被清除材料89包围的束87。束87之间的清除材料89所占据的空间促进氧从纤维束87中所含有的红细胞中分散出来，因而有助于从红细胞中清除氧。
消耗装置的另一个应用是在输血前通过用纯氧或空气冲刷而加回氧。该应用用于特殊的情况，例如大量输血(其中肺对输入血液没有足够的复氧能力)或镰状细胞贫血。
类似地，可根据患者需要用消耗装置获得氧消耗的中间水平或状态，以根据患者需要在输血中获得最佳水平。
在贮藏袋中贮藏之前从RBC中除去氧或者从所述血液中脱去氧包括在本公开内容的范围之内。氧清除剂可用于在血液袋中贮藏之前从RBC中除去氧。本文中使用的“氧清除剂”是在使用条件下与氧不可逆结合或组合的材料。例如，氧可与所述材料的一些成分发生化学反应并且被转变成其他化合物。结合氧的解离速率为零的任何材料都可充当氧清除剂。氧清除剂的实例包括铁粉和有机化合物。在本文中，术语“氧吸附剂”可与氧清除剂互换使用。例如，由Multisorb Technologies(Buffalo，NY)提供氧清除剂。可以以所需的比例混合这样的材料以达到所需的结果。
要理解的是，可以将清除剂并入任何已知形式的贮藏容器和袋(bag)中，例如小袋(sachet)、片(patch)、涂层(coating)、囊(pocket)和包(packet)。
尽管本公开内容详细描述了某些实施方案，应理解的是，对本领域技术人员而言已知存在的改变和修改在本公开内容范围内。因此，本公开内容意在包括全部这样的替代、修改和改变，其在本公开内容所阐述的本发明的范围之内。

Claims (7)

1.氧消耗装置，其包含：
盒；
多个中空纤维，其在所述盒中从其入口延伸至其出口，其中所述中空纤维由氧通透性膜形成并且适于接收和输送红细胞；以及
一定量的氧清除剂，其装在所述盒中并且处于所述多个中空纤维之间并与其相接触。
2.权利要求1的装置，其中所述中空纤维是基本平行的并且从所述入口至所述出口纵向布置在所述盒中。
3.氧消耗装置，其包含：
固体材料的容器，其具有适于接收和排出冲刷气体的进气口和排气口；多个中空纤维，其在所述容器中从其入口延伸至其出口，其中所述中空纤维适于接收和输送红细胞。
4.权利要求3的装置，其中所述中空纤维是基本平行的并且从所述入口至所述出口纵向布置在所述盒中。
5.权利要求3的装置，其还包含与所述容器的所述进气口相连通的冲刷气体源。
6.用于从红细胞中除去氧的方法，其包括：使红细胞通过氧装置，其中所述装置包含：
盒；
多个中空纤维，其在所述盒中从其入口延伸至其出口，其中所述中空纤维适于接收和输送红细胞；以及
一定量的氧清除剂，其装在所述盒中并且处于所述多个中空纤维之间并与其相接触。
7.用于从红细胞中除去氧的方法，其包括：使所述红细胞通过氧消耗装置，其中所述装置包含：
固体材料的容器，其具有适于接收和排出冲刷气体的进气口和排气口；多个中空纤维薄膜，其在所述容器中从其入口延伸至其出口，其中所述中空纤维适于接收和输送红细胞。
CN2010800564451A 2009-10-12 2010-10-12 用于从红细胞中除去氧的氧消耗装置和方法 Pending CN102905522A (zh)

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US8569052B2 (en) 2013-10-29
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US9296990B2 (en) 2016-03-29
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