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    • 3. 发明授权
    • Preservation and restoration of hemoglobin in blood substitutes
    • 血液代用品中血红蛋白的保存和恢复
    • US5051353A
    • 1991-09-24
    • US233303
    • 1988-08-09
    • Lewis P. StrattonMartha C. FarmerAlan S. Rudolph
    • Lewis P. StrattonMartha C. FarmerAlan S. Rudolph
    • A61K38/42
    • A61K38/42
    • A hemoglobin-containing blood substitute preparation is protected from oxtion to methemoglobin. The protected preparation comprises between 10 mM and 60 mM of a compound selected from the group consisting of glutathione (GSH), nicotinamide adenine dinucleotide (NADH), nicotine adenine dinucleotide phosphate (NADPH) and mixtures of these in the aqueous phase of a hemoglobin-containing fluid. Oxidized hemoglobin in a preparation can be restored by adding between 10 mM and 60 mM of a compound selected from the group consisting of glutathione (GSH), nicotinamide adenine dinucleotide (NADH), nicotine adenine dinucleotide phosphate (NADPH) and mixtures of these to a hemoglobin-containing fluid in which the hemoglobin has converted in whole or part to methemoglobin, and storing the fluid at storage temperatures for blood products above the freezing point of the fluid for a time sufficient to convert methemoglobin to hemoglobin.
    • 含血红蛋白的血液替代物制剂被保护免于氧化成高铁血红蛋白。 受保护的制剂包含10mM至60mM的选自谷胱甘肽(GSH),烟酰胺腺嘌呤二核苷酸(NADH),尼古丁腺嘌呤二核苷酸磷酸(NADPH)的化合物及其在血红蛋白 - 含有液体。 通过加入10mM至60mM的选自谷胱甘肽(GSH),烟酰胺腺嘌呤二核苷酸(NADH),尼古丁腺嘌呤二核苷酸磷酸(NADPH)和它们的混合物的化合物组合,可以恢复制剂中的氧化血红蛋白 其中血红蛋白全部或部分转化为高铁血红蛋白,并将流体存储在高于流体凝固点的血液制品的储存温度上足以将高铁血红蛋白转化成血红蛋白的时间。
    • 8. 发明授权
    • Shape stabilized erythrocytes
    • 形状稳定的红细胞
    • US06436705B1
    • 2002-08-20
    • US10046297
    • 2002-01-16
    • Irina B. BakaltchevaAlan S. RudolphBarry J. SpargoSamuel B. LeslieThomas R. Groel
    • Irina B. BakaltchevaAlan S. RudolphBarry J. SpargoSamuel B. LeslieThomas R. Groel
    • C12N508
    • A01N1/0221A01N1/02
    • One aspect of the present invention is a method for storing tissues and cells (typically erythrocytes) having the step of (1) stabilizing the cells with a reversible stabilizing agent. This method typically will have the additional steps of (2) loading the cells with a cryoprotectant, and typically (3) storing the cells in liquid, frozen, or dry state. This method will also typically have the additional step of (4) prior to use, reversing the stabilization reaction. Preferably, the erythrocytes are pre-treated with CO to complex the hemoglobin with CO. It is anticipated that a practical method according to the invention will include reoxygenation of the eryathrocytes, and also washing out reagents prior to in vivo use. Another aspect of the present invention is an erythrocyte that has had its shape stabilized by the reversible crosslinking of proteins in the erythrocyte, such as the structural proteins of the cytoskeleton. Another aspect of the invention is a population of such reversibly cross-linked erythrocytes. Another aspect of the invention is the in vivo use of such erythrocytes, after the reversal of the crosslinking reaction. The use of more gentle, reversible cross-linking as described below is desirable to result in the recovery of erythrocyte deformability and extended post-transfusion survival.
    • 本发明的一个方面是用于存储具有以下步骤的组织和细胞(通常为红细胞)的方法:(1)用可逆稳定剂稳定细胞。 该方法通常将具有(2)用冷冻保护剂加载细胞的另外的步骤,并且通常(3)将细胞储存在液体,冷冻或干燥状态。 该方法通常也将在使用前具有(4)的附加步骤,从而逆转稳定化反应。 优选地,用CO预处理红细胞以使CO与血红蛋白复合。根据本发明的实际方法预期将包括红细胞的再氧化,以及在体内使用之前洗去试剂。 本发明的另一方面是通过红细胞中蛋白质的可逆交联(例如细胞骨架的结构蛋白质)使其形状稳定的红细胞。 本发明的另一方面是这种可逆交联的红细胞的群体。 本发明的另一方面是在反应交联反应后体内使用这种红细胞。 使用如下所述的更温和的可逆交联是期望的,以导致红细胞变形能力的恢复和输血后的生存期延长。
    • 9. 发明授权
    • Applications of reversible crosslinking and co-treatment in stabilization and viral inactivations of erythrocytes
    • 可逆交联和共处理在红细胞稳定化和病毒灭活中的应用
    • US06358678B1
    • 2002-03-19
    • US09022341
    • 1998-02-11
    • Irina B. BakaltchevaAlan S. RudolphBarry J. SpargoSamuel B. LeslieThomas R. Groel
    • Irina B. BakaltchevaAlan S. RudolphBarry J. SpargoSamuel B. LeslieThomas R. Groel
    • A01N102
    • A01N1/0221A01N1/02
    • One aspect of the present invention is a method for storing tissues and cells (typically erythrocytes) having the step of (1) stabilizing the cells with a reversible stabilizing agent. This method typically will have the additional steps of (2) loading the cells with a cryoprotectant, and typically (3) storing the cells in liquid, frozen, or dry state. This method will also typically have the additional step of (4) prior to use, reversing the stabilization reaction. Preferably, the erythrocytes are pre-treated with CO to complex the hemoglobin with CO. It is anticipated that a practical method according to the invention will include reoxygenation of the erythrocytes, and also washing out reagents prior to in vivo use. Another aspect of the present invention is an erythrocyte that has had its shape stabilized by the reversible crosslinking of proteins in the erythrocyte, such as the structural proteins of the cytoskeleton. Another aspect of the invention is a population of such reversibly crosslinked erythrocytes. Another aspect of the invention is the in vivo use of such erythrocytes, after the reversal of the crosslinking reaction. The use of more gentle, reversible cross-linking as described below is desirable to result in the recovery of erythrocyte deformability and extended post-transfusion survival.
    • 本发明的一个方面是用于存储具有以下步骤的组织和细胞(通常为红细胞)的方法:(1)用可逆稳定剂稳定细胞。 该方法通常将具有(2)用冷冻保护剂加载细胞的另外的步骤,并且通常(3)将细胞储存在液体,冷冻或干燥状态。 该方法通常也将在使用前具有(4)的附加步骤,从而逆转稳定化反应。 优选地,红细胞用CO预处理以使CO与血红蛋白复合。根据本发明的实际方法可以预期,包括红细胞的再氧化,以及在体内使用前洗涤试剂。 本发明的另一方面是通过红细胞中蛋白质的可逆交联(例如细胞骨架的结构蛋白质)使其形状稳定的红细胞。 本发明的另一方面是这种可逆交联的红细胞的群体。 本发明的另一方面是在反应交联反应后体内使用这种红细胞。 使用如下所述的更温和的可逆交联是期望的,以导致红细胞变形能力的恢复和输血后的生存期延长。