US4465623A
Expired / Lapsed
US
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Prothrombin complex concentrates, preparation and application thereof
Assignee: Institut Merieux SA
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Filing: 1983-03-17
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Granted: 1984-08-14
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Expires: 2003-03-17
Abstract
Abstract Procedure for the preparation of a concentrate of prothrombinogenic compound. This procedure, in which, starting from a source of prothrombinogenic compound, an adsorption is followed by an elution, is characterized by the fact that a source of prothrombinogenic compound and a source of antithrombin III (or AT III) is placed in contact with an adsorbing agent capable of adsorbing both the prothrombinogenic compound and antithrombin III, and that the foregoing occurs in the presence of heparin, at least during the elution stage, and that elution is carried out with an elution agent capable of eluting the prothrombinogenic compound, the AT III and heparin at the same time. Application of the product obtained, notably to the treatment of blood coagulation difficulties.
Inventors
- 👤 Maryse Chanas
- 👤 Jacques Liautaud
- 👤 Jean Pla
- 👤 Edward Shanbrom
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 04:42
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6429; C12Y; C12Y304/00; C12Y304/21; C12Y304/21005; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/829; Y10S530/83; Y10S530/831
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
76 words
A process for preparing a prothrombinogenic complex concentrate essentially free of activated prothrombinogenic complex comprising contacting a source of prothrombinogenic complex comprising prothrombinogenic complex and antithrombin III with, as an adsorbing agent, alumina gel, in the presence of heparin so that said source and said heparin are adsorbed thereon, and thereafter eluting simultaneously said source and said heparin from said adsorbing agent, said eluting being carried out with a buffer solution at a pH of 7.5-8.5.
Claim 2
Dependent Claim
76 words
A process for preparing a prothrombinogenic complex concentrate essentially free of activated prothrombinogenic complex comprising contacting a source of prothrombinogenic complex comprising prothrombinogenic complex and antithrombin III with, as an adsorbing agent, alumina gel, in the presence of heparin so that said source and said heparin are adsorbed thereon, and thereafter eluting simultaneously said source and said heparin from said adsorbing agent, said eluting being carried out with a buffer solution at a pH of 7.5-8.5.
Claim 3
Dependent Claim
20 words
The process of claim 1 wherein said source comprises a fraction of plasma obtained after the elimination of cryoprecipitate therefrom.
Claim 4
Dependent Claim
11 words
The process of claim 1 wherein said source comprises fresh plasma.
Claim 5
Dependent Claim
12 words
The process of claim 1 wherein said source comprises Cohn's fraction IV.
Claim 6
Dependent Claim
21 words
The process of claim 1 which includes adding heparin to said source prior to contacting said source with said adsorption agent.
Claim 7
Dependent Claim
25 words
The process of claim 1 wherein said heparin is present in an amount ranging from about 0.1 to 1 I.U. per ml. of said source.
Claim 8
Dependent Claim
19 words
The process of claim 1 wherein said contacting step is carried out at a temperature lower than ambient temperature.
Claim 9
Dependent Claim
21 words
The process of claim 7 wherein said contacting step is carried out at a temperature ranging from 0° to 15° C.
Claim 10
Dependent Claim
21 words
The process of claim 7 wherein said contacting step is carried out at a temperature ranging from 2° to 8° C.
Claim 11
Dependent Claim
22 words
The process of claim 1 wherein the eluting step is carried out at a temperature ranging from 0° C. to ambient temperature.
Claim 12
Dependent Claim
15 words
The process of claim 10 wherein the eluting step is carried out at ambient temperature.
Claim 13
Dependent Claim
40 words
The process of claim 1 which includes, subsequent to the eluting step, purifying the resulting eluate with polyethylene glycol at a pH of about 7 and at a temperature lower than ambient temperature so as to precipitate undesirable proteins therefrom.
Claim 14
Dependent Claim
34 words
The process of claim 12 which also includes removing said precipitate, adjusting the pH of the resulting supernatant to 4.8 to 5.2 and thereafter adding sufficient polyethylene glycol to precipitate said prothrombinogenic complex concentrate.
Claim 15
Dependent Claim
138 words
A process for preparing a prothrombinogenic complex concentrate essentially free of activated prothrombinogenic complex comprising contacting a source of prothrombinogenic complex comprising prothrombinogenic complex and antithrombin III present in an amount sufficient to stabilize said prothrombinogenic complex with, as an adsorbing agent, alumina gel, in the presence of heparin so that said source and said heparin are adsorbed thereon, eluting simultaneously said source and said heparin from said adsorbing agent, said eluting being carried out with a buffer solution at a pH of 7.5-8.5, purifying the resulting eluate with polyethylene glycol at a pH of about 7 and at a temperature lower than ambient temperature so as to precipitate undesirable proteins therefrom, removing said precipitate, adjusting the pH of the resulting supernatant to 4.8 to 5.2 and thereafter adding sufficient polyethylene glycol to precipitate said prothrombinogenic complex concentrate.
Claim 16
Dependent Claim
138 words
A process for preparing a prothrombinogenic complex concentrate essentially free of activated prothrombinogenic complex comprising contacting a source of prothrombinogenic complex comprising prothrombinogenic complex and antithrombin III present in an amount sufficient to stabilize said prothrombinogenic complex with, as an adsorbing agent, alumina gel, in the presence of heparin so that said source and said heparin are adsorbed thereon, eluting simultaneously said source and said heparin from said adsorbing agent, said eluting being carried out with a buffer solution at a pH of 7.5-8.5, purifying the resulting eluate with polyethylene glycol at a pH of about 7 and at a temperature lower than ambient temperature so as to precipitate undesirable proteins therefrom, removing said precipitate, adjusting the pH of the resulting supernatant to 4.8 to 5.2 and thereafter adding sufficient polyethylene glycol to precipitate said prothrombinogenic complex concentrate.
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) | 1987-08-14 | 1988-02-13 | 1988-08-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-08-14 | 1992-02-13 | 1992-08-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-08-14 | 1996-02-13 | 1996-08-14 | $7700.00 | Window Closed / Lapsed |