Biopure Corporation

Other

Texas Tech University System

Biopure Corportion

Mario J Feola

Carl W Rausch

Jan S Simoni

Peter C Canizaro, Deceased

Grace Simoni

Peter C Canizaro

The present invention relates to novel methods of using blood substitutes to treat acute blood loss and novel pharmaceutical compositions comprising blood substitutes. Blood substitutes useful for the methods of the present invention can (1) induce expression of erythropoietin as tested in a cell culture under normoxic conditions, and/or (2) induce erythropoiesis under normoxic conditions as measured by (a) a decrease in the doubling time of the subject's hematocrit or hemoglobin, and/or (b) an increase in the subject's circulating erythropoietin level. Blood substitutes useful for the pharmaceutical compositions of the present invention can (1) stabilize HIF-1 alpha expression, and/or (2) down regulate NF-kappa B. Preferably, the blood substitutes are cross-linked hemoglobin blood substitutes, or more preferably, cross-linked hemoglobins that comprise a hemoglobin that is cross-linked intramolecularly with periodate-oxidized ATP, cross-linked intermolecularly with periodate-oxidized adenosine, and conugated with reduced glutathione.

Methods of treating acute blood loss

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.

Ultra pure hemoglobin solutions and blood-substitutes

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.

Ultra pure hemoglobin solutions and blood substitutes

An improved blood substitute comprises purified hemoglobin, preferably bovine, cross-linked intramolecularly with periodate-oxidized ATP (o-ATP) and intermolecularly with periodate-oxidized adenosine (o-adenosine), combined with reduced glutathione (GSH), and optionally enriched with mannitol, non-electrolytes, and/or electrolytes. The blood substitute has prolonged intravascular persistence, can sustain plasma volume, has low oxygen affinity, can work as a physiological oxygen carrier, has vasodilator activity and can reduce the vasoconstriction that follows hemorrhage. A method of treating a human afflicted with acute blood loss and/or a sickling crisis of sickle cell anemia comprises intravenously administrating to the human an effective volume of the blood substitute.

Blood substitute

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.

Growing community of inventors

Lubbock, TX, United States of America

Mario J Feola