Abstract: The present invention relates to the surprising discovery that previous hemoglobin-based drug purification methodologies do not remove sufficient endotoxins exposures at the various steps which may complex with the hemoglobin protein. These complexed endotoxins can result in serious health complications (e.g. development of cardiac lesions for one). Additionally, varied endotoxin types and concentration contributes to batch-to-batch variability during hemoglobin-based drug manufacture. Endotoxins are not as much of an issue for peptides as compared to larger protein complexes. Accordingly, the instant disclosure is directed to a purification process using single use systems in many process steps including high performance chromatography systems thereby removing endotoxins while keeping processing costs low.

Abstract: The present disclosure relates to methods and systems for manufacturing stabilized hemoglobin solutions. The methods and systems incorporate single use components for endotoxin-free formulation. The hemoglobin solutions may be substantially endotoxin-free and/or highly deoxygenated.

Abstract: The present invention relates to the surprising discovery that previous hemoglobin-based drug purification methodologies do not remove sufficient endotoxins exposures at the various steps which may complex with the hemoglobin protein. These complexed endotoxins can result in serious health complications (e.g. development of cardiac lesions for one). Additionally, varied endotoxin types and concentration contributes to batch-to-batch variability during hemoglobin-based drug manufacture. Endotoxins are not as much of an issue for peptides as compared to larger protein complexes. Accordingly, the instant disclosure is directed to a purification process using single use systems in many process steps including high performance chromatography systems thereby removing endotoxins while keeping processing costs low.

Abstract: A composition of chemically purified soluble mannans from legumes' seeds (e.g. Ceratonia siliqua, Cæsalpinia spinosa Trigonelle foenum-graecum, and Cyamopsis tetragonolobus) and their use in the assembly of palatable dietary supplements is disclosed herein. The fractionation process provides high-quality physiologically soluble, chemically modified and purified homogeneous size polysaccharide fibers, devoid of natural impurities, for example proteins, alkaloids, glycoalkaloids, and/or environmental impurities including heavy metals, agricultural residues and microbial toxins. This process provides hypoallergenic dietary fibers devoid of any potential allergens, cytotoxins, and gastrointestinal toxins.

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: 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 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: 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: 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 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 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: 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 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: 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 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: 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: A method is disclosed treating a tumor in a host by administering an ultrapurified polymerized hemoglobin solution to the host and thereafter administering ionizing radiation, such as X-rays, to the tumor. In a particularly preferred embodiment, the hemoglobin is bovine hemoglobin.

Abstract: A blood substitute and plasma expander comprising a cross-linked, substantially endotoxin-free homoglobin 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.