Hemoglobin-based oxygen carriers and methods of making and using thereof
AssigneesOhio State Innovation Foundation, The Regents of the University of California
InventorsAndre PALMER, Pedro J. CABRALES AREVALO, Xiangming GU, Chintan SAVLA
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Abstract
Disclosed are hemoglobin-based oxygen carriers (HBOCs) that comprise a polymer-functionalized polymerized hemoglobin, such as a polyalkylene oxide (PAO)-functionalized polymerized hemoglobin, as well as compositions comprising these HBOCs (e.g., dissolved or dispersed in an aqueous carrier) and methods of making and using thereof.
Claims40
A hemoglobin-based oxygen carrier (HBOC) comprising a polymer-functionalized polymerized hemoglobin;
- wherein the polymer-functionalized polymerized hemoglobin has a weight average molecular weight of from 500 kDa to 2,000 kDa, as determined by size exclusion (SEC) HPLC.
A method of producing a hemoglobin-based oxygen carrier (HBOC), the method comprising:
- (i) contacting hemoglobin with a multifunctional cross-linking agent to form a solution comprising polymerized hemoglobin;
- (ii) filtering the solution comprising polymerized hemoglobin by ultrafiltration against a first filtration membrane having a pore size that separates the polymerized hemoglobin from low-molecular weight hemoglobin species, reactants, and reaction byproducts, thereby forming a retentate fraction comprising the polymerized hemoglobin and a permeate fraction comprising impurities;
- (iii) covalently conjugating one or more polymers to the polymerized hemoglobin to form a solution comprising a polymer-functionalized polymerized hemoglobin;
- and
- (iv) filtering the solution comprising the polymer-functionalized polymerized hemoglobin by ultrafiltration against a second filtration membrane having a pore size that separates the polymer-functionalized polymerized hemoglobin from low-molecular weight impurities, reactants, and reaction byproducts, thereby forming a retentate fraction comprising the polymer-functionalized polymerized hemoglobin and a permeate fraction comprising impurities.
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Dependencies are inferred from the claim text.