Patent US4136093A successfully refreshed from Google Patents.
US4136093A
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Hemoglobin preparation with increased oxygen release
Assignee: Biotest AG
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Filing: 1977-04-21
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Granted: 1979-01-23
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Expires: 1997-04-21
Abstract
Abstract Hemoglobin preparation suited for intravenous injection with increased oxygen release in relation to erythrocytes or hemoglobin solution, comprising a substantially pyrogen-free condensation product of hemoglobin and pyridoxal phosphate having a retention time in the blood vessel from about 2 to 9 hours. It is produced by washing human erythrocytes at least four times with a weakly alkaline solution, then hemolyzing and treating the material with a cation exchange resin in the H+ form until the pH value has dropped to about 5 to 5.5, separating the material from resin and any precipitated stroma, diluting the material to a hemoglobin concentration of about 5 to 9%, adjusting the pH to about 7 to 9, displacing any oxygen therein, and adding about 0.25 to 1.25 g of pyridoxal-5-phosphate per liter of hemoglobin solution of 5 to 9% concentration. To increase the retention time still further there can be included the further steps of treating the solution with a borohydride and then with a dialdehyde thereby to cross-link the hemoglobin molecules in said erythrocytes, and separating uncross-linked hemoglobin from the residual solution of the desired cross-linked hemoglobin.
Inventors
- 👤 Klaus Bonhard
- 👤 Uwe Boysen
- 👤 Hans Schleubner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 18:45
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/795; C07K14/805; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/829
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
108 words
A method of manufacturing a hemoglobin preparation, comprising washing human erythrocytes at least four times with a weakly alkaline solution, hemolyzing the erythrocytes in a solvent consisting essentially of water, treating the hemolyzate material with a cation exchange resin in the H+ form until the pH value has dropped to about 5 to 5.5, separating the material from resin and any precipitated stroma, diluting the material with water to a hemoglobin concentration of about 5 to 9%, adjusting the pH to about 7 to 9, displacing any oxygen therein, and adding about 0.25 to 1.25 g of pyridoxal-5-phosphate per liter of hemoglobin solution of 5 to 9% concentration.
Claim 2
Independent Claim
108 words
A method of manufacturing a hemoglobin preparation, comprising washing human erythrocytes at least four times with a weakly alkaline solution, hemolyzing the erythrocytes in a solvent consisting essentially of water, treating the hemolyzate material with a cation exchange resin in the H+ form until the pH value has dropped to about 5 to 5.5, separating the material from resin and any precipitated stroma, diluting the material with water to a hemoglobin concentration of about 5 to 9%, adjusting the pH to about 7 to 9, displacing any oxygen therein, and adding about 0.25 to 1.25 g of pyridoxal-5-phosphate per liter of hemoglobin solution of 5 to 9% concentration.
Claim 3
Dependent Claim
27 words
A method according to claim 1, wherein prior to hemolysis the erythrocytes are first treated with about 4 to 12 g of beta-propiolactone per liter of erythrocytes.
Claim 4
Dependent Claim
25 words
A method according to claim 1, wherein glucose monohydrate is added in about 22 g per liter of solution prior to addition of the pyridoxal-5-phosphate.
Claim 5
Dependent Claim
22 words
A method according to claim 1, wherein the pH of the solution following addition of the pyridoxal-5-phosphate is adjusted to about 7.6.
Claim 6
Dependent Claim
41 words
A method according to claim 2, wherein glucose monohydrate is added in about 22 g per liter of solution prior to addition of the pyridoxal-5-phosphate, and the pH of the solution following addition of the pyridoxal-5-phosphate is adjusted to about 7.6.
Claim 7
Dependent Claim
61 words
A method according to claim 1, including the further steps of treating the solution with a borohydride and then with a dialdehyde thereby to cross-link the hemoglobin molecules in said erythrocytes, and separating uncross-linked hemoglobin from the residual solution of the desired cross-linked hemoglobin which latter then has an effective retention time of about 4 to 9 hours following intravenous administration.
Claim 8
Dependent Claim
28 words
A method according to claim 6, wherein the borohydride is sodium borohydride and it is employed in about 5 to 10 times the molar amount of the pyridoxal-5-phosphate.
Claim 9
Dependent Claim
32 words
A method according to claim 6, wherein the dialdehyde is of the formula O═CH--(CH 2 ) 1-6 --CH═O and it is employed in about 9 times the molar amount of the hemoglobin.
Claim 10
Dependent Claim
23 words
A method according to claim 6, wherein the pH of the residual solution of the cross-linked hemoglobin solution is adjusted to about 7.6.
Claim 11
Dependent Claim
24 words
A method according to claim 9, wherein to the solution of pH about 7.6 glucose monohydrate is added in about 22 g per liter.
Claim 12
Dependent Claim
110 words
A method according to claim 2, including the further steps of treating the solution with sodium borohydride in about 5 to 10 times the molar amount of the pyridoxal-5-phosphate and then with a dialdehyde of the formula O═CH--(CH 2 ) 1-6 --CH═O in about 9 times the molar amount of the hemoglobin in said erythrocytes thereby to cross-link the hemoglobin molecules, separating uncross-linked hemoglobin from the residual solution of the desired cross-linked hemoglobin, adjusting the pH of the residual solution to about 7.6 and adding about 22 g per liter of glucose monohydrate, whereby the solution has an effective retention time of about 4 to 9 hours following intravenous administration.
Claim 13
Dependent Claim
9 words
The product produced by the process of claim 1.
Claim 14
Dependent Claim
9 words
The product produced by the process of claim 6.
References Cited (Backward Citations)
US4001200A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1982-01-22 | 1982-07-24 | 1983-01-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1986-01-22 | 1986-07-24 | 1987-01-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1990-01-22 | 1990-07-24 | 1991-01-23 | $7700.00 | Window Closed / Lapsed |