US4536391A
Expired / Lapsed
US
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Process for preparing urokinase complex
Assignee: Otsuka Pharmaceutical Co Ltd
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Filing: 1983-11-15
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Granted: 1985-08-20
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Expires: 2003-11-15
Abstract
Abstract This invention provides a process for preparing a fibrin-adsorable protein-urokinase complex characterized by reacting a protein adsorbable by fibrin with urokinase in the presence of a protein coupling reagent represented by the formula <IMAGE> wherein R is phenylene or cycloalkylene, A is lower alkylene, B is lower alkylene which may optionally be substituted by lower alkylthio or phenyl-lower alkylthio, and l, m and n are each 0 or 1 provided that l, m and n are not 0 at the same time. The complex is useful as a thrombolytic agent.
Inventors
- 👤 Wasei Miyazaki
- 👤 Tsuneo Sato
- 👤 Yasuo Nakayama
- 👤 Tadao Sato
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 05:03
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/44; C07D207/444; C07D207/448; C07D207/452; C07D207/46; C12; C12N; C12N11/00; C12N11/02; C12N11/06; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6456; C12N9/6462; C12Y; C12Y304/00; C12Y304/21; C12Y304/21073; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
80 words
A plasmin heavy chain urokinase complex prepared by a process comprising reacting a plasmin heavy chain with urokinase in the presence of a protein coupling reagent represented by the formula ##STR32## wherein R is phenylene or cycloalkylene, A is lower alkylene, B is lower alkylene which may optionally be substituted by lower alkylthio or phenyl-lower alkylthio, and l, and m and n are each 0 or 1 provided that l, m and n are not 0 at the same time.
Claim 2
Dependent Claim
80 words
A plasmin heavy chain urokinase complex prepared by a process comprising reacting a plasmin heavy chain with urokinase in the presence of a protein coupling reagent represented by the formula ##STR32## wherein R is phenylene or cycloalkylene, A is lower alkylene, B is lower alkylene which may optionally be substituted by lower alkylthio or phenyl-lower alkylthio, and l, and m and n are each 0 or 1 provided that l, m and n are not 0 at the same time.
Claim 3
Dependent Claim
31 words
A plasmin heavy chain urokinase complex as defined in claim 1 which comprises 1 to 5 moles of the urokinase and 1 mole of the plasmin heavy chain as coupled therewith.
Claim 4
Dependent Claim
39 words
A plasmin heavy chain urokinase complex as defined in claim 2 wherein the protein coupling reagent is a compound of the formula ##STR33## wherein A and B each represent lower alkylene, l and m each are 0 or 1.
Claim 5
Dependent Claim
59 words
A plasmin heavy chain urokinase complex as defined in claim 2 wherein the protein-coupling reagent is a compound of the formula ##STR34## wherein A is lower alkylene, B is lower alkylene which is substituted by lower alkylthio or phenyl-lower alkylthio, and l and m are 0 or 1, and the urokinase is low molecular weight-urokinase or high molecular weight-urokinase.
Claim 6
Dependent Claim
18 words
A plasmin heavy chain urokinase complex as defined in claim 3 wherein the urokinase is low molecular weight-urokinase.
Claim 7
Dependent Claim
81 words
A plasmin heavy chain urokinase complex as defined in claim 5 prepared by the coupling reaction between the plasmin heavy chain and urokinase carried out in an aqueous solution, physiological saline or a buffer having a pH of 4 to 10 at 0° to 40° C. for several minutes to about 24 hours using about 0.3 to about 4 moles of the plasmin heavy chain and about 1 to about 50 moles of the protein coupling reagent per mole of urokinase.
Claim 8
Dependent Claim
82 words
A plasmin heavy chain urokinase complex as defined in claim 5 prepared by the coupling reaction between the plasmin heavy chain protein and urokinase carried out in an aqueous solution, physiological saline or a buffer having a pH of 4 to 10 of 0° to 40° C. for several minutes to about 24 hours using about 0.3 to about 4 moles of the plasmin heavy chain and about 1 to about 50 moles of the protein coupling reagent per mole of urokinase.
Claim 9
Dependent Claim
73 words
A plasmin heavy chain urokinase complex as defined in claim 6 prepared by the coupling reaction between the plasmin heavy chain and urokinase carried out in a buffer having a pH of 6 to 8 at room temperature for several minutes to about 24 hours using about 0.5 to about 2 moles of the plasmin heavy chain and about 3 to about 20 moles of the protein coupling reagent per mole of urokinase.
Claim 10
Dependent Claim
73 words
A plasmin heavy chain urokinase complex as defined in claim 7 prepared by the coupling reaction between the plasmin heavy chain and urokinase carried out in a buffer having a pH of 6 to 8 at room temperature for several minutes to about 24 hours using about 0.5 to about 2 moles of the plasmin heavy chain and about 3 to about 20 moles of the protein coupling reagent per mole of urokinase.
Claim 11
Dependent Claim
29 words
A plasmin heavy chain urokinase complex as defined in claim 7 which comprises 1 mole of the urokinase and 1 mole of the plasmin heavy chain as coupled therewith.
Claim 12
Dependent Claim
50 words
A plasmin heavy chain urokinase complex as defined in claim 10 which contains about 1 mole of plasmin heavy chain coupled with 1 mole of low molecular weight-urokinase wherein the protein coupling reagent is a compound of the formula ##STR35## and which has a molecular weight of 80,000 to 90,000.
Claim 13
Dependent Claim
49 words
A plasmin heavy chain urokinase complex as defined in claim 10 which contains about 1 mole of plasmin heavy chain coupled with 1 mole of low molecular weight-urokinase wherein the protein coupling reagent is a compound of the formula ##STR36## and which has a molecular weight of about 90,000.
Claim 14
Dependent Claim
49 words
A plasmin heavy chain arokinase complex as defined in claim 10 which contains about 1 mole of plasmin heavy chain coupled with 1 mole of low molecular weight-urokinase wherein the protein coupling reagent is a compound of the formula ##STR37## and which has a molecular weight of about 90,000.
Claim 15
Dependent Claim
49 words
A plasmin heavy chain urokinase complex as defined in claim 10 which contains about 1 mole of plasmin heavy chain coupled with 1 mole of low molecular weight-urokinase wherein the protein coupling reagent is a compound of the formula ##STR38## and which has a molecular weight of about 90,000.
Claim 16
Dependent Claim
30 words
A plasmin heavy chain urokinase complex as defined in claim 2 wherein R is cycloalkylene and m is 1, and the urokinase is low molecular weight-urokinase or high molecular weight-urokinase.
Claim 17
Dependent Claim
26 words
A plasmin heavy chain urokinase complex as defined in claim 2 wherein m is 0, and the urokinase is low molecular weight-urokinase or high molecular weight-urokinase.
Claim 18
Dependent Claim
32 words
A pharmaceutical composition for treating thrombosis containing the plasmin heavy chain-urokinase complex as defined in claim 1 in an amount effective for treating thrombosis in combination with a pharmaceutically acceptable, non-toxic carrier.
References Cited (Backward Citations)
US4029767A
Cited
US4349630A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-08-19 | 1989-02-18 | 1989-08-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-08-19 | 1993-02-18 | 1993-08-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-08-19 | 1997-02-18 | 1997-08-20 | $7700.00 | Window Closed / Lapsed |