US4001401A
Expired / Lapsed
US
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Blood substitute and blood plasma expander comprising polyhemoglobin
Assignee: QUEST BLOOD SUBSTITUTE Inc
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Filing: 1975-02-02
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Granted: 1977-01-04
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Expires: 1995-02-02
Abstract
Abstract This invention concerns a pharmaceutical composition comprising cross-linked, stromal-free hemoglobin mixed with a physiologically acceptable carrier useful as a blood substitute for carrying and supplying oxygen to tissues and organs, and as a blood plasma expander.
Inventors
- 👤 Pieter Bonsen
- 👤 Myron B. Laver
- 👤 Kent C. Morris
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 15:07
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/795; C07K14/805; A; A61; A61K; A61K38/00; A61M; A61M1/00; A61M1/36; A61M1/3693; A61M2202/00; A61M2202/04; A61M2202/0413; A61M2202/0415; A61M2202/0429; A61M2202/0433
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
48 words
A pharmaceutical composition useful as a blood substitute and blood plasma expander comprising a therapeutically effective amount of cross-linked, stromal-free hemoglobin, soluble in aqueous and physiological fluids, capable of reversibly binding a ligand and having a molecular weight of 64,000 to 1,000,000, mixed with a pharmaceutically acceptable carrier.
Claim 2
Dependent Claim
48 words
A pharmaceutical composition useful as a blood substitute and blood plasma expander comprising a therapeutically effective amount of cross-linked, stromal-free hemoglobin, soluble in aqueous and physiological fluids, capable of reversibly binding a ligand and having a molecular weight of 64,000 to 1,000,000, mixed with a pharmaceutically acceptable carrier.
Claim 3
Dependent Claim
16 words
A pharmaceutical composition according to claim 1 wherein the hemoglobin used for the cross-linking is deoxyhemoglobin.
Claim 4
Dependent Claim
16 words
A pharmaceutical composition according to claim 1 wherein the hemoglobin used for the cross-linking is oxyhemoglobin.
Claim 5
Dependent Claim
19 words
A pharmaceutical composition according to claim 1 wherein said hemoglobin is soluble in aqueous and pharmaceutically acceptable liquid carriers.
Claim 6
Dependent Claim
26 words
A pharmaceutical composition according to claim 1 wherein said carrier is a member selected from the group consisting of crystalloid, colloidal, polymeric solutions, and mixtures thereof.
Claim 7
Dependent Claim
24 words
A pharmaceutical composition according to claim 1 wherein the carrier is a liquid and the composition contains from 2 to 15% of said hemoglobin.
Claim 8
Dependent Claim
26 words
A pharmaceutical composition according to claim 1 wherein said cross-linked, stromal-free hemoglobin has oxygen transport capacity and reversible oxygen binding capacity when mixed with the carrier.
Claim 9
Dependent Claim
25 words
A pharmaceutical composition according to claim 1 wherein said cross-linked hemoglobin has an increased plasma residence time 2 to 7 times greater than non-crosslinked hemoglobin.
Claim 10
Dependent Claim
35 words
A pharmaceutical composition according to Claim 1, wherein the cross-linked, stromal-free hemoglobin has a partial oxygen pressure at half-saturation, P 50 , between 2.5 mm Hg and 120 mm Hg at physiological temperature and pH.
Claim 11
Dependent Claim
27 words
A pharmaceutical composition according to claim 1 wherein the hemoglobin is cross-linked with a member selected from the group consisting of glutaraldehyde, hexamethylene diisocyanate and butadiene diepoxide.
Claim 12
Dependent Claim
34 words
A pharmaceutical composition according to claim 1 wherein the pharmaceutically acceptable carrier is a crystalloid selected from the group consisting of saline, a mixture consisting of saline and glucose, and sodium citrate-citric acid-dextrose solution.
Claim 13
Dependent Claim
33 words
A pharmaceutical composition according to claim 1 wherein the pharmaceutically acceptable carrier is a member selected from the group consisting of poly(ethylene oxide), polyacrylamide, polyvinyl pyrrolidone, polyvinyl alcohol, and ethylene oxide-polypropylene glycol condensates.
Claim 14
Dependent Claim
34 words
A pharmaceutical composition according to claim 1 wherein the pharmaceutically acceptable carrier is a member selected from the group consisting of polysaccharides, dextran, gum arabic, plasma proteins, albumin, pectin, fluid gelatin and hydroxyethyl starch.
Claim 15
Independent Claim
62 words
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.
Claim 16
Independent Claim
62 words
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.
Claim 17
Independent Claim
49 words
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.
Claim 18
Independent Claim
49 words
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.
Claim 19
Independent Claim
44 words
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.
Claim 20
Independent Claim
44 words
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.
Claim 21
Independent Claim
39 words
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.
Claim 22
Independent Claim
39 words
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.
Claim 23
Dependent Claim
63 words
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.
Claim 24
Dependent Claim
63 words
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.
Claim 25
Independent Claim
115 words
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) 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.
Claim 26
Independent Claim
115 words
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) 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.
Claim 27
Dependent Claim
42 words
A method for increasing the shelf life and in vivo life according to claim 19 wherein the polymerized, cross-linked, stromal-free hemoglobin has an intravascular persistence in an animal at least twice that of hemoglobin, and has an osmolarity substantially equal to blood.
References Cited (Backward Citations)
US3788948A
Cited
US3560475A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-01-04 | 1980-07-05 | 1981-01-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-01-04 | 1984-07-05 | 1985-01-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-01-04 | 1988-07-05 | 1989-01-04 | $7700.00 | Window Closed / Lapsed |