Diaspirin crosslinked pegylated hemoglobin
AssigneeWilliam Schindler
InventorsKim D. Vandegriff, Ashok Malavalli, Scott D. Olsen
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Abstract
PEGylated diaspirin-crosslinked hemoglobin conjugates having high oxygen affinity are described which have enhanced nitrite reductase activity to deliver oxygen, carbon monoxide, nitric oxide or mixtures thereof to tissues to treat various diseases and conditions.
Claims20
A β,β-intramolecularly-crosslinked polyalkylene oxide hemoglobin tetramer conjugate having a P50 ranging from about 2 to 5 mmHg as measured at 37° C. and pH 7.4, wherein the hemoglobin conjugate when fully deoxygenated at 25° C. exhibits a maximal nitrite reductase activity that is at least 10-fold greater than that of deoxygenated stroma-free hemoglobin when measured under the same conditions, wherein the hemoglobin is conjugated to on average about 7 to about 11 polyalkylene oxide molecules per tetramer.
A β,β-intramolecularly-crosslinked polyalkylene oxide hemoglobin conjugate having a P50 ranging from about 2 to 5 mmHg as measured at 37° C. and pH 7.4, wherein the hemoglobin conjugate when fully deoxygenated at 25° C. exhibits a maximal nitrite reductase activity that is at least 10-fold greater than that of deoxygenated stroma-free hemoglobin when measured under the same conditions, the β,β-intramolecularly-crosslinked polyalkylene oxide hemoglobin conjugate having the formula:
- wherein:
- Hb is a hemoglobin bis(3,5-dibromosalicyl) fumarate crosslinked at two (382 lysine residues of the hemoglobin molecule,
- S is a thiol of the hemoglobin,
- R3 is an alkylene or phenylene group,
- X is hydroxy, aryloxy, or C1-C20 alkoxy,
- m is about 7 to about 11, and
- n is the average number of oxyethylene units of a PEG having an average molecular weight of about 2,000 to about 20,000 Daltons.
Dependencies are inferred from the claim text.