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公开(公告)号：US5753616A
公开(公告)日：1998-05-19
申请号：US478004
申请日：1995-06-07
申请人： Carl W. Rausch , Maria S. Gawryl , Robert A. Houtchens , Anthony J. Laccetti , William R. Light
发明人： Carl W. Rausch , Maria S. Gawryl , Robert A. Houtchens , Anthony J. Laccetti , William R. Light
IPC分类号： A01N1/02 , A61J1/00 , A61J1/05 , A61K38/00 , A61M1/36 , B32B15/08 , B32B27/08 , C07K14/805 , A61K38/42
CPC分类号： C07K14/805 , A01N1/02 , A01N1/0221 , B32B15/08 , B32B27/08 , A61J1/05 , A61K38/00 , A61M1/3693 , A61M2202/0433
摘要： A method for producing a stable polymerized hemoglobin blood-substitute from blood. The method of this invention includes mixing blood with an anticoagulant to form a blood solution, washing the red blood cells in the blood solution and then separating the washed red blood cells from the white blood cells. This method also includes disrupting the red blood cells to release hemoglobin and form a hemoglobin solution, which is then treated by high performance liquid chromatography to form a hemoglobin eluate. The hemoglobin eluate is then deoxygenated, contacted with a first sulfhydryl compound to form an oxidation-stabilized deoxygenated hemoglobin solution, and mixed with a cross-linking agent to form a polymerization reaction mixture, which is then polymerized. The polymerized hemoglobin solution is then diafiltered with a physiologic solution and with a sulfhydryl compound, whereby the polymerized hemoglobin solution is made physiologically acceptable, and whereby the sulfhydryl compound scavenges oxygen, to form a stable polymerized hemoglobin blood-substitute.
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2.发明授权
公开(公告)号：US5840852A
公开(公告)日：1998-11-24
申请号：US458916
申请日：1995-06-02
申请人： Carl W. Rausch , Maria S. Gawryl , Robert A. Houtchens , Anthony J. Laccetti , William R. Light
发明人： Carl W. Rausch , Maria S. Gawryl , Robert A. Houtchens , Anthony J. Laccetti , William R. Light
CPC分类号： C07K14/805 , A01N1/02 , A01N1/0226 , A01N1/0231 , A61K38/42 , B32B15/08 , B32B27/08 , A61J1/05
摘要： The present invention relates to a method of therapeutically, or prophylactically, treating a vertebrate to increase tissue oxygenation, or maintain issue oxygenation, in tissue of a vertebrate wherein the tissue has a reduced red blood cell flow, and wherein the vertebrate has a normovolemic blood volume and at least a normal systemic vascular resistance. The method comprises introducing into the circulatory system of the vertebrate at least one dose of hemoglobin.
摘要翻译： 本发明涉及一种在脊椎动物组织中治疗或预防性地治疗脊椎动物以增加组织氧合或维持问题氧合的方法，其中所述组织具有减少的红细胞流，并且其中所述脊椎动物具有正常血容量的血液 体积和至少一个正常的全身血管阻力。 该方法包括向脊椎动物的循环系统中引入至少一种剂量的血红蛋白。
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公开(公告)号：US5955581A
公开(公告)日：1999-09-21
申请号：US484775
申请日：1995-06-07
申请人： Carl W. Rausch , Maria S. Gawryl , Robert A. Houtchens , Anthony J. Laccetti , William R. Light
发明人： Carl W. Rausch , Maria S. Gawryl , Robert A. Houtchens , Anthony J. Laccetti , William R. Light
CPC分类号： A01N1/02 , A01N1/0221 , A01N1/0226 , B32B15/08 , B32B27/08 , C07K14/805 , A61J1/05 , A61K38/00 , A61M1/3693 , A61M2202/0433
摘要： A method for producing a stable polymerized hemoglobin blood-substitute from blood. The method of this invention includes mixing blood with an anticoagulant to form a blood solution, washing the red blood cells in the blood solution and then separating the washed red blood cells from the white blood cells. This method also includes disrupting the red blood cells to release hemoglobin and form a hemoglobin solution, which is then treated by high performance liquid chromatography to form a hemoglobin eluate. The hemoglobin eluate is then deoxygenated, contacted with a first sulfhydryl compound to form an oxidation-stabilized deoxygenated hemoglobin solution, and mixed with a cross-linking agent to form a polymerization reaction mixture, which is then polymerized. The polymerized hemoglobin solution is then diafiltered with a physiologic solution and with a sulfhydryl compound, whereby the polymerized hemoglobin solution is made physiologically acceptable, and whereby the sulfhydryl compound scavenges oxygen, to form a stable polymerized hemoglobin blood-substitute.
摘要翻译： 从血液制备稳定的聚合血红蛋白血液代用品的方法。 本发明的方法包括将血液与抗凝血剂混合以形成血液溶液，洗涤血液中的红细胞，然后从白细胞中分离洗涤的红细胞。 该方法还包括破坏红细胞以释放血红蛋白并形成血红蛋白溶液，然后通过高效液相色谱法处理以形成血红蛋白洗脱液。 然后将血红蛋白洗脱液脱氧，与第一巯基化合物接触以形成氧化稳定的脱氧血红蛋白溶液，并与交联剂混合以形成聚合反应混合物，然后将其聚合。 然后将聚合的血红蛋白溶液用生理溶液和巯基化合物进行渗滤，由此将聚合的血红蛋白溶液制成生理学上可接受的，由此巯基化合物清除氧气，形成稳定的聚合血红蛋白血液替代品。
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公开(公告)号：US5952470A
公开(公告)日：1999-09-14
申请号：US477916
申请日：1995-06-07
IPC分类号： C07K1/14 , C07K14/805 , C07K1/30
CPC分类号： C07K14/805
摘要： A method for separating unmodified hemoglobin from cross-linked hemoglobin in a hemoglobin solution. The method involves contacting the hemoglobin solution with a least one dissociating agent to form a dissociation solution wherein unmodified tetrameric hemoglobin is dissociated to form hemoglobin dimers. The hemoglobin dimers are then separated from the dissociation solution, while retaining the cross-linked hemoglobin in the dissociation solution.
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公开(公告)号：US5895810A
公开(公告)日：1999-04-20
申请号：US487288
申请日：1995-06-07
CPC分类号： C07K14/805 , A01N1/02 , A01N1/0263 , B32B15/08 , B32B27/08 , A61J1/05 , A61K38/00
摘要： The present invention relates to a composition of matter comprising a stable polymerized hemoglobin solution, useful for forming blood-substitutes, and to a method for forming said stable polymerized hemoglobin solution. The stable polymerized hemoglobin solution, and derived blood-substitutes, of this invention comprise polymerized hemoglobin and a sulfhydryl compound, both in solution, wherein the sulfhydryl compound stabilizes the polymerized hemoglobin.The method of this invention comprises deoxygenating hemoglobin in a hemoglobin solution and then mixing the deoxygenated hemoglobin with a sulfhydryl compound to form an oxidation-stabilized, deoxygenated hemoglobin solution. Subsequently, the oxidation-stabilized deoxygenated hemoglobin solution is mixed with a cross-linking agent to form a polymerization reaction mixture, which is then polymerized to form a stable polymerized hemoglobin solution.
摘要翻译： 本发明涉及包含可用于形成血液代用品的稳定聚合血红蛋白溶液的物质组合物以及形成所述稳定聚合血红蛋白溶液的方法。 本发明的稳定的聚合血红蛋白溶液和衍生的血液代用品在溶液中都包含聚合的血红蛋白和巯基化合物，其中巯基化合物稳定聚合的血红蛋白。 本发明的方法包括在血红蛋白溶液中脱氧血红蛋白，然后将脱氧血红蛋白与巯基化合物混合以形成氧化稳定的脱氧血红蛋白溶液。 随后，将氧化稳定的脱氧血红蛋白溶液与交联剂混合以形成聚合反应混合物，然后将其聚合以形成稳定的聚合血红蛋白溶液。
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公开(公告)号：US07041800B1
公开(公告)日：2006-05-09
申请号：US10018599
申请日：2000-07-07
IPC分类号： C07K14/805 , A61B19/02
CPC分类号： A61J1/05 , A01N1/02 , A01N1/0263 , A61K38/00 , A61K38/42 , A61M1/0272 , B32B15/08 , B32B27/08 , B32B27/32 , C07K14/805
摘要： The invention relates to a method for preserving the stability of a hemoglobin blood substitute comprising maintaining the hemoglobin blood substitute in an atmosphere substantially free of oxygen. The method for preserving a deoxygenated hemoglobin blood substitute comprises maintaining the deoxygenated hemoglobin blood substitute in an oxygen barrier film overwrap package. In one embodiment, the package comprises a transparent laminate material comprising an oxygen barrier layer and a polyolefin layer, wherein the laminant has a thickness of between about 0.001 and about 0.01 inches (or about 0.0254 to about 0.254 millimeters) and an oxygen permeability of less than about 0.01 cubic centimeters per 100 square inches (or about 0.01 cc per 645 square centimeters) over 24 hours at 1 atmosphere and at about 23° C. The oxygen barrier layer comprises ethylene vinyl alcohol. Aso provided herein is a preserved deoxygenated hemoglobin blood substitute comprises a deoxygenated hemoglobin blood substitute and an oxygen barrier film overwrap package. The package comprises a transparent laminant material comprising an oxygen barrier layer and a polyolefin layer. Said oxygen barrier layer has an oxygen permeability of less than about 0.01 cubic centimeters per 100 square inches (or about 0.01 cc per 645 square centimeters) over 24 hours at 1 atmosphere and at about 27° C. room temperature, wherein the deoxygenated hemoglobin blood substitute is sealed within the overwrap package. In one embodiment, the oxygen barrier layer comprises ethylene vinyl alcohol.
摘要翻译： 本发明涉及一种保持血红蛋白血液替代品的稳定性的方法，包括将血红蛋白血液替代物维持在基本上不含氧的气氛中。 保存脱氧血红蛋白血液替代物的方法包括将脱氧血红蛋白血液替代物保持在氧阻隔膜外包装中。 在一个实施方案中，包装包括包含氧阻隔层和聚烯烃层的透明层压材料，其中层压剂具有约0.001至约0.01英寸（或约0.0254至约0.254毫米）的厚度，并且氧渗透性较小 超过约0.01立方厘米每100平方英寸（或约0.01cc / 645平方厘米），在1个大气压和约23℃下经24小时。氧气阻隔层包括乙烯乙烯醇。 本文提供的是保存的脱氧血红蛋白血液替代物，其包含脱氧血红蛋白血液替代物和氧阻隔膜外包装。 该包装包括透明层压材料，其包含氧阻隔层和聚烯烃层。 所述氧阻隔层在1个大气压和约27℃的室温下经24小时内具有小于约0.01立方厘米/ 100平方英寸（或约0.01cc / 645平方厘米）的透氧性，其中脱氧血红蛋白血液 替代品密封在外包装包装内。 在一个实施方案中，氧阻隔层包含乙烯乙烯醇。
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公开(公告)号：US07041799B1
公开(公告)日：2006-05-09
申请号：US10018529
申请日：2000-07-07
IPC分类号： C07K14/805 , A61B19/02
CPC分类号： A61J1/05 , A01N1/02 , A01N1/0263 , A61K35/00 , A61K38/42 , B32B7/02 , B32B15/08 , B32B27/08 , B32B27/18 , B32B27/304 , B32B27/32 , B32B27/36 , B32B2250/24 , B32B2264/102 , B32B2307/412 , B32B2307/7244 , B32B2439/80 , B32B2535/00 , C07K14/805
摘要： The invention relates to a method for preserving the stability of a hemoglobin blood substitute comprising maintaining the hemoglobin blood substitute in an atmosphere substantially free of oxygen. The method for preserving the deoxygenated hemoglobin blood substitute comprises maintaining the deoxygenated blood substitute in an oxygen barrier film overwrap package, wherein at least one face of the overwrap package comprises a transparent laminate material and wherein at least one other face of the overwrap package comprises a foil laminate material. The preserved deoxygenated hemoglobin blood substitute comprises a deoxygenated hemoglobin blood substitute and an oxygen barrier film overwrap package wherein at least one face of the overwrap package comprises a transparent laminate material and wherein at least one other face of the overwrap package comprises a foil laminate material.
摘要翻译： 本发明涉及一种保持血红蛋白血液替代品的稳定性的方法，包括将血红蛋白血液替代物维持在基本上不含氧的气氛中。 用于保存脱氧血红蛋白血液替代物的方法包括将脱氧血液替代物保持在氧阻隔膜外包装中，其中外包裹包装的至少一个面包括透明层压材料，并且其中外包裹包装的至少另一个面包括 箔层压材料。 保存的脱氧血红蛋白血液替代物包括脱氧血红蛋白血液替代物和氧阻隔膜外包装，其中外包装包装的至少一个面包括透明层压材料，并且其中外包裹包装的至少另一个面包括箔层压材料。
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公开(公告)号：US07001715B2
公开(公告)日：2006-02-21
申请号：US10090428
申请日：2002-02-28
CPC分类号： A61K35/18
摘要： Red blood cells are purified by separating whole blood, such as by centrifugation, to form a red blood cell fraction and a liquid fraction. The whole blood can be defibrinated or treated to prevent coagulation prior to separation. Preferably, the whole blood is bovine blood. The red blood cell fraction is then diafiltered to purify the red blood cells. The purified red blood cells can then be lysed to form a lysate of purified red blood cells. The purified red blood cells and the lysate of purified red blood cells are suitable for use in producing hemoglobin blood substitute.
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9.发明授权Use of defibrinated blood for manufacture of hemoglobin-based oxygen carrier 有权使用去纤颤的血液制造基于血红蛋白的氧载体公开(公告)号：US07553613B2
公开(公告)日：2009-06-30
申请号：US11289048
申请日：2005-11-29
CPC分类号： A61K38/42 , C12N5/0641 , C12N2509/00 , Y10S530/812 , Y10S530/829
摘要： Red blood cells are purified by defibrinating whole blood and then filtering the defibrinated whole blood, whereby at least a portion of a plasma component is separated from the red blood cells to form a suspension of red blood cells, thereby purifying the red blood cells. Whole blood is defibrinated by, for example, using a chemical coagulating agent or mechanical agitation. Separation of the plasma component from red blood cells can be completed by, for example, diafiltration. The suspension of red blood cells can then be employed to produce a hemoglobin-based oxygen carrier.
摘要翻译： 通过除血全血，然后过滤去纤维化的全血来纯化红细胞，由此将血浆成分的至少一部分与红细胞分离，形成红细胞的悬浮液，从而纯化红细胞。 全血通过例如使用化学凝结剂或机械搅动来脱纤维蛋白。 可以通过例如渗滤来完成血浆成分与红细胞的分离。 然后可以使用红细胞的悬浮液来产生基于血红蛋白的氧载体。
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公开(公告)号：US06288027B1
公开(公告)日：2001-09-11
申请号：US09348881
申请日：1999-07-07
IPC分类号： C07K14805
CPC分类号： B32B1/02 , A01N1/02 , A01N1/0263 , A61J1/05 , A61J1/10 , A61K38/42 , A61M1/0272 , B32B15/08 , B32B15/082 , B32B27/08 , B32B27/306 , B32B27/32 , B32B37/153 , B32B2307/412 , B32B2307/7244 , B32B2439/80 , C07K14/805
摘要： The invention relates to a method for preserving the stability of a hemoglobin blood substitute comprising maintaining the hemoglobin blood substitute in an atmosphere substantially free of oxygen. The invention also involves a method for producing a stable polymerized hemoglobin blood-substitute from blood. The method of this invention includes mixing blood with an anticoagulent to form a blood solution, washing the red blood cells in the blood solution and then separating the washed red blood cells from the white blood cells. This method also includes disrupting the red blood cells to release hemoglobin and form a hemoglobin solution, which is then treated by high performance liquid chromatography to form a hemoglobin eluate. The hemoglobin eluate is then deoxygenated, contacted with a first sulfhydryl compound to form an oxidation-stabilized deoxygenated hemoglobin solution, and mixed with a cross-linking agent to form a polymerization reaction mixture, which is then polymerized. The polymerized hemoglobin solution is then diafiltered with a physiologic solution and with a sulfhydryl compound, whereby the polymerized hemoglobin solution is made physiologically acceptable, and whereby the sulfhydryl compound scavenges oxygen, to form a stable polymerized hemoglobin blood-substitute, which is then packaged and stored in an atmosphere substantially free of oxygen.
摘要翻译： 本发明涉及一种保持血红蛋白血液替代品的稳定性的方法，包括将血红蛋白血液替代物维持在基本上不含氧的气氛中。 本发明还涉及从血液制备稳定的聚合血红蛋白血液代用品的方法。 本发明的方法包括将血液与抗凝血剂混合以形成血液溶液，洗涤血液中的红细胞，然后从白细胞中分离洗涤的红细胞。 该方法还包括破坏红细胞以释放血红蛋白并形成血红蛋白溶液，然后通过高效液相色谱法处理以形成血红蛋白洗脱液。 然后将血红蛋白洗脱液脱氧，与第一巯基化合物接触以形成氧化稳定的脱氧血红蛋白溶液，并与交联剂混合以形成聚合反应混合物，然后将其聚合。 然后将聚合的血红蛋白溶液与生理溶液和巯基化合物进行渗滤，由此将聚合的血红蛋白溶液制成生理学上可接受的，由此巯基化合物清除氧气，形成稳定的聚合血红蛋白血液替代物，然后将其包装， 储存在基本上不含氧的气氛中。
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