Abstract: A blood substitute and plasma expander comprising a cross-linked, substantially endotoxin-free hemoglobin solution and process for preparing same. The process comprises fractionating whole blood, separating out a stromal-free, sterile hemoglobulin solution, chromatographically separating endotoxins from said hemoglobin solution and crosslinking the resulting endotoxin-free hemoglobin solution.

Abstract: 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.

Abstract: 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.

Abstract: At least one dose of polymerized hemoglobin is administered a vertebrate to increase tissue oxygenation, or maintain issue oxygenation, in an organ of a vertebrate wherein the organ 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 hemoglobin increases function of the organ.

Abstract: 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.

Abstract: 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 with a cross-linking agent to form a polymerization reaction mixture, which is then polymerized.

Abstract: A method for producing a purified hemoglobin product includes loading a hemoglobin solution onto an anion exchange chromatography column. At least one tris(hydroxymethyl) aminomethane acetate buffer solution is injected into the column. The buffer solution has a pH lower than that of the column, whereby a purified hemoglobin product elutes from the column. In one embodiment, the hemoglobin solution initially can be equilibrated at a pH of greater than about 8.7. In another embodiment, contaminants can be removed by equilibrating the column with at least about eleven column void volumes of buffer solution at an intermediate pH of between about 8.2 and about 8.6, to thereby form a stepped pH gradient. In still another embodiment, all buffer solutions employed are tris(hydroxymethyl) aminomethane acetate.

Abstract: 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.

Abstract: 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.

Abstract: An enzyme preparation that exhibits cephalosporin chloroperoxidase activity is isolatable from a microorganism species of the Rathayibacter genus. This enzyme preparation can convert cephalexin to cefaclor in a single step. A particular, unique microorganism that can provide the cephalosporin chloroperoxidase enzyme preparation is Rathayibacter biopuresis.

Abstract: A blood substitute and plasma expander comprising a cross-linked, substantially endotoxin-free hemoglobin solution and process for preparing same. The process comprises fractionating whole blood, separating out a stromal-free, sterile hemoglobin solution, chromatographically separating endotoxins from said hemoglobin solution and crosslinking the resulting endotoxin-free hemoglobin solution.

Abstract: 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.

Abstract: 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.

Abstract: An enzyme preparation that exhibits cephalosporin haloperoxidase activity is isolatable from a microorganism species of the Rathayibacter genus. This enzyme preparation can convert cephalexin to a halogenated cephalosporin antibiotic in a single step. A particular, unique microorganism that can provide the cephalosporin haloperoxidase enzyme preparation is Rathayibacter biopuresis.

Abstract: 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.

Abstract: A method for removing a prion from a solution comprising the prion and at least one additional biomolecule, comprising directing the solution through an anion-exchange chromatography column under conditions that cause a gradient elution, whereby the prion is separated from at least one of the biomolecules, thereby causing said biomolecule to be collected in an eluate fraction that is distinct from an eluate fraction that includes the prion. In one embodiment, the gradient is a pH gradient, for example, a step gradient. The prion can be a causal agent for a spongiform encephalopathy, such as Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinken syndrome, scrapie, or bovine spongiform encephalopathy.

Abstract: A method is disclosed treating a tumor in a host by administering a nonemulsified ultrapurified polymerized hemoglobin solution to the host and also administering a chemotherapeutic agent to the host. In a particularly preferred embodiment, the hemoglobin is bovine hemoglobin.

Abstract: 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.

Abstract: An enzyme preparation that exhibits cephalosporin chloroperoxidase activity is isolatable from a microorganism species of the Rathayibacter genus. This enzyme preparation can convert cephalexin to cefaclor in a single step. A particular, unique microorganism that can provide the cephalosporin chloroperoxidase enzyme preparation is Rathayibacter biopuresis.

Abstract: 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.