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Patent US4336248A successfully refreshed from Google Patents.
US4336248A
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Preparation of coupled hemoglobin molecules
Assignee: Biotest AG
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Filing: 1975-10-20
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Granted: 1982-06-22
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Expires: 1995-10-20
Abstract
Abstract Hemoglobin molecules are coupled so as to increase their intravascular residence times without significantly diminishing their oxygen transport ability. This is achieved by coupling hemoglobin molecules to one another and/or to serum proteins and gelatin derivatives using dialdehydes such as aliphatic dialdehydes of 3 to 8 carbon atoms, optionally followed by addition of pyridoxal phosphate. The desired material isolated by ammonium sulfate precipitation, the sulfate being added before, simultaneously with, or after the dialdehyde. Solution of the precipitate followed by dialysis and/or ion exchange can also be undertaken.
Inventors
- 👤 Klaus Bonhard
- 👤 Uwe Boysen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 22:43
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/795; C07K14/805; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
95 words
A chemically modified, stable hemoglobin preparation suitable for blood replacement and for organ perfusion, comprising hemoglobin molecules coupled to one another or to another protein selected from the group consisting of serum proteins and gelatin derivatives by a coupling reagent comprising an aliphatic dialdehyde having 3 to 8 carbon atoms, molar ratio of the coupling reagent to the hemoglobin being about 6:1 to about 18:1, the preparation having a capacity to transport oxygen corresponding approximately to that of free hemoglobin, and a blood residence time which is at least about twice that of free hemoglobin.
Claim 2
Dependent Claim
95 words
A chemically modified, stable hemoglobin preparation suitable for blood replacement and for organ perfusion, comprising hemoglobin molecules coupled to one another or to another protein selected from the group consisting of serum proteins and gelatin derivatives by a coupling reagent comprising an aliphatic dialdehyde having 3 to 8 carbon atoms, molar ratio of the coupling reagent to the hemoglobin being about 6:1 to about 18:1, the preparation having a capacity to transport oxygen corresponding approximately to that of free hemoglobin, and a blood residence time which is at least about twice that of free hemoglobin.
Claim 3
Dependent Claim
42 words
A process for producing a hemoglobin preparation according to claim 1, comprising adding to substantially oxygen-free hemoglobin the dialdehyde coupling reagent in a molar ratio of the dialdehyde to the hemoglobin of about 6:1 to about 18:1 and isolating the coupled hemoglobin.
Claim 4
Dependent Claim
56 words
The process of claim 2 comprising adding pyridoxal phosphate to the reaction mixture of the hemoglobin and the dialdehyde and wherein, after the pyridoxal phosphate has been added, the coupled hemoglobin is isolated as a precipitate by salting out with ammonium sulfate and, then, the ammonium sulfate in the product is partly replaced with sodium chloride.
Claim 5
Dependent Claim
23 words
The process of claim 2 wherein the dialdehyde is added as a solution in at least one of water and a lower alkanol.
Claim 6
Dependent Claim
20 words
The process of claim 4 wherein the aldehyde is added to and mixed with the hemoglobin under a nitrogen atmosphere.
Claim 7
Dependent Claim
20 words
The process of claim 2 wherein the coupled hemoglobin is isolated as a precipitate by salting out with ammonium sulfate.
Claim 8
Dependent Claim
17 words
The process of claim 6 wherein the ammonium sulfate is present in the hemoglobin prior to coupling.
Claim 9
Dependent Claim
16 words
The process of claim 4 wherein ammonium sulfate is added to the hemoglobin with the dialdehyde.
Claim 10
Dependent Claim
17 words
The process of claim 6 wherein the ammonium sulfate is added to the hemoglobin preparation after coupling.
Claim 11
Dependent Claim
18 words
The process of claim 6 including the further steps of dissolving the precipitate, and removing ammonium sulfate therefrom.
Claim 12
Dependent Claim
23 words
The process of claim 1 wherein serum albumin momlecules are present along with the hemoglobin molecules and are coupled to the hemoglobin molecules.
Claim 13
Dependent Claim
23 words
The process of claim 2 wherein gelatin derivative molecules are present along with the hemoglobin molecules and are coupled to the hemoglobin molecules.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-06-21 | 1985-12-21 | 1986-06-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-06-21 | 1989-12-21 | 1990-06-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-06-21 | 1993-12-21 | 1994-06-22 | $7700.00 | Window Closed / Lapsed |