US4857636A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Pasteurizable, freeze-driable hemoglobin-based blood substitute
Assignee: Canada, NATIONAL DEFENCE OF HER MAJESTY'S CANADIAN, Minister of
•
Filing: 1988-04-29
•
Granted: 1989-08-15
•
Expires: 2008-04-29
Abstract
Abstract The present specification describes a process by which a blood substitute (hereinafter referred to as "HemoSafe") is derived from uniformly stabilized monomers and polymers of deoxyhemoglobin in its tight (T) conformation, with oxygen affinity similar to that of human blood. Two classes of HemoSafe are derived respectively from animal-hemoglobin and humanhemoglobin. HemoSafe (animal) differs from HemoSafe (human) in that it is free of polymers in order to reduce potential immunogenicity if used in man. Both types of HemoSafe may be derived in the following manner. The stabilized deoxyhemoglobins are converted to their carbonmonoxy derivatives (CO-HemoSafe) which are then stable under pasteurization conditions to render them viral disease transmission-free. CO-HemoSafes are stable for 2 months at 56° C. in either the solution or the freeze-dried state. For transfusion CO-HemoSafes are easily oxygenated under sterile conditions by photoconversion yielding oxy-HemoSafe. In addition a transfusable met-hemoglobin derivative for treatment of cyanide poisoning, is derived by converting oxy-HemoSafe to met-HemoSafe.
Inventors
- 👤 Jen-Chang Hsia
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 19:27
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/795; C07K14/805; A; A61; A61K; A61K38/00; A61K38/16; A61K38/41; A61K38/42; A61L; A61L2/00; A61L2/02; A61L2/04; A61P; A61P7/00; A61P7/08; A61L2103/00; A61L2103/05
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
92 words
A stabilized hemoglobin product consisting essentially of tetrameric hemoglobin units stabilized against dissociation into dimers, and stabilized against conformational change between the T-conformation and the R-conformation upon formation of aqueous preparations thereof, said tetrameric units having covalent chemical linkages between globin chains of the sub-units to effect the stabilization, the covalent linkages being secondary amino linkages, formed by reaction of the hemoglobin with an aldehyde produced by oxidative ring opening of an oligosaccharide having at least two sugar moieties, followed by reduction of the so-formed Schiff base linkages to secondary amino linkages.
Claim 2
Dependent Claim
92 words
A stabilized hemoglobin product consisting essentially of tetrameric hemoglobin units stabilized against dissociation into dimers, and stabilized against conformational change between the T-conformation and the R-conformation upon formation of aqueous preparations thereof, said tetrameric units having covalent chemical linkages between globin chains of the sub-units to effect the stabilization, the covalent linkages being secondary amino linkages, formed by reaction of the hemoglobin with an aldehyde produced by oxidative ring opening of an oligosaccharide having at least two sugar moieties, followed by reduction of the so-formed Schiff base linkages to secondary amino linkages.
Claim 3
Dependent Claim
14 words
Stabilized hemoglobin product according to claim 1 which is conformationally stabilized into the T-conformation.
Claim 4
Dependent Claim
18 words
Stabilized hemoglobin product according to claim 1 wherein the oligosaccharide has up to 7 sugar moieties per molecule.
Claim 5
Dependent Claim
12 words
Stabilized hemoglobin product according to claim 3 wherein the oligosaccharide is raffinose.
Claim 6
Dependent Claim
14 words
Stabilized hemoglobin product according to claim 1 wherein the hemoglobin is of human origin.
Claim 7
Dependent Claim
14 words
Stabilized hemoglobin product according to claim 1 wherein the hemoglobin is of animal origin.
Claim 8
Dependent Claim
37 words
A stabilized hemoglobin product comprising a plurality of said stabilized tetrameric hemoglobin units according to claim 1, covalently linked together to form a polymeric hemoglobin product in which each hemoglobin unit has conformational stability and dissociative stability.
Claim 9
Dependent Claim
19 words
A stabilized polymeric hemoglobin product according to claim 7, wherein each hemoglobin unit thereof is stabilized in the T-conformation.
Claim 10
Dependent Claim
51 words
A stabilized polymeric hemoglobin product according to claim 8 and having a composition such that from 20-25% of the constituents are hemoglobin tetrameric units, 50-60% of the constituents are hemoglobin oligomers of 2-4 tetrameric hemoglobin units, 20-25% of the constituents are single hemoglobin tetramers, and 1-2% are dimers of hemoglobin subunits.
Claim 11
Dependent Claim
76 words
A stabilized hemoglobin product consisting essentially of tetrameric hemoglobin units stabilized against dissociation into dimers, and stabilized against conformational change between the T-conformation and the R-conformation upon formation of aqueous preparations thereof, said tetrameric units having covalent chemical linkages between globin chains of the sub-units to effect the stabilization, the stabilized hemoglobin product being the reaction product of hemoglobin with an aldehyde derived from oxidative ring opening of an oligosaccharide having at least two sugar moieties.
Claim 12
Dependent Claim
76 words
A stabilized hemoglobin product consisting essentially of tetrameric hemoglobin units stabilized against dissociation into dimers, and stabilized against conformational change between the T-conformation and the R-conformation upon formation of aqueous preparations thereof, said tetrameric units having covalent chemical linkages between globin chains of the sub-units to effect the stabilization, the stabilized hemoglobin product being the reaction product of hemoglobin with an aldehyde derived from oxidative ring opening of an oligosaccharide having at least two sugar moieties.
Claim 13
Dependent Claim
14 words
The stabilized hemoglobin product of claim 10, which is conformationally stabilized into the T-conformation.
Claim 14
Dependent Claim
18 words
The stabilized hemoglobin product of claim 11, wherein the oligosaccharide has up to 7 sugar moieties per molecule.
Claim 15
Dependent Claim
12 words
The stabilized hemoglobin product of claim 12, wherein the oligosaccharide is raffinose.
Claim 16
Dependent Claim
14 words
The stabilized hemoglobin product of claim 10, wherein the hemoglobin is of human origin.
Claim 17
Dependent Claim
14 words
The stabilized hemoglobin product of claim 10 wherein the hemoglobin is of animal origin.
References Cited (Backward Citations)
US3925344A
Cited
US4336248A
Cited
US4061736A
Cited
US4001200A
Cited
US4473496A
Cited
WO1984000696A1
Cited
US4529719A
Cited
US4600531A
Cited
US4584130A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-08-14 | 1993-02-13 | 1993-08-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-08-14 | 1997-02-13 | 1997-08-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-08-14 | 2001-02-13 | 2001-08-15 | $7700.00 | Window Closed / Lapsed |