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US3864478A
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Storage-stable hemoglobin solutions and method for their preparation
Assignee: Biotest AG
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Filing: 1973-10-03
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Granted: 1975-02-04
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Expires: 1993-10-03
Abstract
Abstract Method for obtaining a storage-stable, infusionable and hepatitis-safe hemoglobin solution having a stabilized 2,3diphospho-glycerate level which method comprises A. TREATING A STARTING MATERIAL CONTAINING HUMAN ERYTHROCYTE WITH A DILUTE SOLUTION OF Beta -PROPIOLACTONE AT TEMPERATURES BETWEEN 5* AND 15*C. to result in a mixture containing Beta propiolactone in an amount of from 4 to 12 g per liter of erythrocyte sediment, thereafter B. TREATING THE MIXTURE WITH A NEUTRAL OR WEAKLY ALKALINE WASHING SOLUTION TO WASH OUT THE EXCESS Beta -PROPIOLACTONE AND ITS REACTION PRODUCTS, C. THEN TREATING THE RESULTING HEMOLYSATE, AFTER MIXING THE ERYTHROCYTES IN DISTILLED WATER, WITH A CATION EXCHANGE RESIN IN H -form, until the pH-value has dropped to 5.0 to 5.5, to result in precipitation of a stroma-lipid mass, D. SEPARATING THE HEMOLYSATE FROM THE RESIN AND THE PRECIPITATED STROMA MASS BY CENTRIFUGING, E. OPTIONALLY ADJUSTING THE DESIRED HEMOGLOBIN CONCENTRATION BY DILUTING WITH WATER, F. OPTIONALLY ADDING AGENTS FOR THE CONTROL OF THE ISOTONICITY AND FOR THE STABILIZATION OF PH-value and ferrous protein bound iron content and G. RECOVERING THE HEMOGLOBIN SOLUTION BY STERILE FILTRATION.
Inventors
- 👤 Klaus Bonhard
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 17:52
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: 16
Claim 1
Independent Claim
139 words
METHOD FOR OBTAINING A HEMOGLOBIN SOLUTION HAVING A STABILIZED 2,3-DIOPHOSPHO-GLYCERATE LEVEL WHICH METHOD COMPRISES A. TREATING A STARTING MATERIAL CONTAINING HUMAN ERYTHROCYTES WITH A DILUTED SOLUTION OF B-PROPIOLACTONE AT TEMPERATURES BETWEEN 5* AND 15*C. TO RESULT IN A MIXTURE CONTAINING B-PROPIOLACTONE IN AN AMOUNT OF FROM 4 TO 12 G PER LITER OF ERYTHROCYTE SEDIMENT, THEREAFTER TREATING THE MIXTURE WITH A NEUTRAL OR WEAKLY ALKALINE WASHING SOLUTION TO WASH OUT THE EXCESS B-PROPIOLACTONE AND ITS REACTION PRODUCTS, C. THEN MIXING THE ERYTHOCYTES WITH DISTILLED WATER TO FORM A HEMOLYSATE WHICH IS TREATED WITH A CATION EXCHANGE RESIN IN H+-FORM, UNTIL THE PH-VALUE HAS DROPPED TO 5.0 TO 5.5, TO RESULT IN PRECIPITATION OF A STROMA-LIPID MASS, D. SEPARATING THE HEMOLYSATE FROM THE RESIN AND THE PRECIPITATED STROMA MASS BY CENTRIFUGING, AND E. RECOVERING THE HEMOGLOBIN SOLUTION BY STERILE FILTRATION.
Claim 2
Dependent Claim
139 words
METHOD FOR OBTAINING A HEMOGLOBIN SOLUTION HAVING A STABILIZED 2,3-DIOPHOSPHO-GLYCERATE LEVEL WHICH METHOD COMPRISES A. TREATING A STARTING MATERIAL CONTAINING HUMAN ERYTHROCYTES WITH A DILUTED SOLUTION OF B-PROPIOLACTONE AT TEMPERATURES BETWEEN 5* AND 15*C. TO RESULT IN A MIXTURE CONTAINING B-PROPIOLACTONE IN AN AMOUNT OF FROM 4 TO 12 G PER LITER OF ERYTHROCYTE SEDIMENT, THEREAFTER TREATING THE MIXTURE WITH A NEUTRAL OR WEAKLY ALKALINE WASHING SOLUTION TO WASH OUT THE EXCESS B-PROPIOLACTONE AND ITS REACTION PRODUCTS, C. THEN MIXING THE ERYTHOCYTES WITH DISTILLED WATER TO FORM A HEMOLYSATE WHICH IS TREATED WITH A CATION EXCHANGE RESIN IN H+-FORM, UNTIL THE PH-VALUE HAS DROPPED TO 5.0 TO 5.5, TO RESULT IN PRECIPITATION OF A STROMA-LIPID MASS, D. SEPARATING THE HEMOLYSATE FROM THE RESIN AND THE PRECIPITATED STROMA MASS BY CENTRIFUGING, AND E. RECOVERING THE HEMOGLOBIN SOLUTION BY STERILE FILTRATION.
Claim 3
Dependent Claim
36 words
Method as claimed in claim 1, wherein, in step (a) of the method, from 6 to 16 g. of Beta -propiolactone are used in solutions of 1.2 to 3.2 g/100 ml per 1.5 liter erythrocyte sediment.
Claim 4
Dependent Claim
51 words
Method as claimed in claim 1, wherein prior to the sterile filtration of step (e) of the method, the solution present after the stroma separation of step (d) is frozen in stick-shaped form and then thawed in vertical position and the melt rich in hemo-globin is seperated from the ice block.
Claim 5
Dependent Claim
20 words
Method as claimed in claim 1, wherein the Beta -propiolactone treatment of step (a) is performed at 10* to 12*C.
Claim 6
Dependent Claim
24 words
Method as claimed in claim 1, wherein the washing step (b) for the removal of excess Beta -propiolactone is repeated at least four times.
Claim 7
Dependent Claim
19 words
Method as claimed in claim 1, wherein the washing step (b) is effected with a solution of sodium bicarbonate.
Claim 8
Dependent Claim
13 words
Method as claimed in claim 6, wherein said solution is 3.8% sodium bicarbonate.
Claim 9
Dependent Claim
19 words
Method as claimed in claim 1, wherein the washing step (b) is effected with a solution of sodium chloride.
Claim 10
Dependent Claim
12 words
Method as claimed in claim 8, wherein said solution is 1.6sodium chloride.
Claim 11
Dependent Claim
21 words
Method as claimed in claim 1, wherein the cation exchange resin used in step (c) is a polystyrenesulfonate resin in H-form.
Claim 12
Dependent Claim
27 words
Method as claimed in claim 1, including the additional step between steps (d) and (e) of adjusting the isotonicity by adding glucose, sodium acetate or sodium bicarbonate.
Claim 13
Dependent Claim
25 words
Method as claimed in claim 1, including the additional step between steps (d) and (e) of adjusting the pH-value to about 7.4 with caustic soda.
Claim 14
Dependent Claim
23 words
Method as claimed in claim 1, wherein sterile filtration of step (e) is effected by use of cellulose-asbestos filters or cellulose acetate discs.
Claim 15
Dependent Claim
16 words
A hemoglobin solution having a stabilized 2,3-diphospho-glycerate level, prepared by the method claimed in claim 1.
Claim 16
Dependent Claim
16 words
A hemoglobin solution having a stabilized 2,3-diphospho-glycerate level, prepared by diphospho-glycerate method claimed in claim 3.
References Cited (Backward Citations)
US2527210A
Cited
US3634290A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1978-02-03 | 1978-08-05 | 1979-02-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1982-02-03 | 1982-08-05 | 1983-02-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1986-02-03 | 1986-08-05 | 1987-02-04 | $7700.00 | Window Closed / Lapsed |