Hemoglobin-polysaccharide conjugates
AssigneeHemosol Inc.
InventorGordon J. Adamson
Life of this patent
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Abstract
Hemoglobin conjugates useful as a hemoglobin-based oxygen carriers are prepared by reacting hemoglobin with oxidatively ring-opened polysaccharides such as hydroxyethyl starch or dextran, and storing the resultant conjugate under conditions which allow it to transform to a lower molecular weight product, after conjugation. The conjugate is then reductively stabilized to form secondary amino bonds between the hemoglobin and the polysaccharide, and formulated as an HBOC.
Claims16
A polysaccharide-hemoglobin conjugate useful as an oxygen transporter, comprising hemoglobin covalently linked through secondary amine linkages between amino groups on the hemoglobin and residues of aldehyde groups on the polysaccharide produced by oxidative saccharide ring-opening thereof, the secondary amine linkages having been formed by reaction of said amino groups and said aldehyde groups in a first stage to form Schiff base linkages, and in a second, subsequent stage by reduction to effect stabilization, the conjugate having no detectable residual unbound hemoglobin and no detectable residual amounts of components of molecular weight higher than about 500 kDa.
The conjugate of claim l wherein the polysaccharide is hydroxyethyl starch or dextran
A process of preparing a hemoglobin based oxygen carrier which comprises reacting an oxidatively ring-opened polysaccharide carrying aldehyde groups, with hemoglobin, to form a conjugate thereof, maintaining the conjugate under controlled conditions of aqueous solution with predetermined pH to effect controlled molecular weight reduction and molecular weight re-distribution of the conjugate, stabilizing the conjugate by reduction of the Schiff base linkages, between the polysaccharide and the hemoglobin to stable, secondary amine linkages, and recovering a solution of the polysaccharide-hemoglobin conjugate so formed which has no detectable unbound hemoglobin residue and no detectable product residue of molecular weight greater than about 500-600 kDa.
Dependencies are inferred from the claim text.