Blood substitute and blood plasma expander comprising polyhemoglobin

A method for increasing the volume of the blood circulatory system wherein the method comprises transfusing into a system having a decreased volume, a quantity of a blood volume expander which consists of cross-linked, stromal-free hemoglobin having a molecular weight of 64,000 to 1,000,000, in an isotonic solution, and wherein the quantity is transfused in an effective amount to increase said volume.

A method for the treatment of shock which comprises administering into the circulatory system of a mammal in shock, a blood plasma substitute consisting of cross-linked, stromalfree hemoglobin having a molecular weight of 64,000 to 1,000,000, in an isotonic solution and in an effective amount to alleviate said shock.

A method for maintaining an isolated mammalian organ in a viable state which method comprises perfusing the organ with an effective amount of a perfusate consisting of crosslinked, stromal-free hemoglobin having a molecular weight of 64,000 to 1,000,000, mixed with a pharmaceutically acceptable carrier.

A method for supplying oxygen to tissues and organs comprising transfusing an effective amount of oxygenated cross-linked, stromal-free hemoglobin having a molecular weight of 64,000 to 1,000,000, into the circulatory system for supplying oxygen to said tissues and organs.

A pharmaceutical composition useful as a blood substitute and blood plasma expander wherein the composition comprises a therapeutically effective amount of polymerized, cross-linked, stromal-free hemoglobin, soluble in aqueous and physiological fluids, capable of reversibly binding a ligand, with said cross-linked hemoglobin formed by reacting 1 equivalent of hemoglobin with 2.5 to 300 equivalents of a cross-linking reagent, mixed with a pharmaceutically acceptable carrier.

A method for increasing the shelf-life and in vivo life of hemoglobin which method comprises the steps of separating erythrocytes from blood, lysing the erythrocytes to disrupt the cellular wall of the erythrocytes, isolating hemoglobin from the lysed erythrocytes substantially free of cellular wall material and stroma, polymerizing the isolated, stromal-free hemoglobin by cross-linking with a polyfunctional cross-linking agent to form polymerized, cross-linked, stromal-free hemoglobin, soluble in aqueous and physiological fluids, capable of reversibly binding a ligand, and having the general formula poly (Hb).sub.n wherein Hb is the hemoglobin monomer and n is 4 to 60, and wherein the polymerized hemoglobin has an increased shelf life and an increased in vivo life in animals.