JP2820699B2 - 血栓溶解剤 - Google Patents
血栓溶解剤Info
- Publication number
- JP2820699B2 JP2820699B2 JP63233362A JP23336288A JP2820699B2 JP 2820699 B2 JP2820699 B2 JP 2820699B2 JP 63233362 A JP63233362 A JP 63233362A JP 23336288 A JP23336288 A JP 23336288A JP 2820699 B2 JP2820699 B2 JP 2820699B2
- Authority
- JP
- Japan
- Prior art keywords
- lys
- urokinase
- pro
- plasminogen
- prourokinase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000003527 fibrinolytic agent Substances 0.000 title description 3
- 229960000103 thrombolytic agent Drugs 0.000 title description 2
- 108010073863 saruplase Proteins 0.000 claims abstract description 75
- 238000002347 injection Methods 0.000 claims abstract description 24
- 239000007924 injection Substances 0.000 claims abstract description 24
- 108010087750 lysyl-plasminogen Proteins 0.000 claims abstract description 22
- 238000001802 infusion Methods 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims description 10
- 102000009123 Fibrin Human genes 0.000 claims description 8
- 108010073385 Fibrin Proteins 0.000 claims description 8
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 8
- 239000002552 dosage form Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 229950003499 fibrin Drugs 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 230000002934 lysing effect Effects 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 3
- 108010039627 Aprotinin Proteins 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 229960004405 aprotinin Drugs 0.000 claims 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 claims 1
- 230000002537 thrombolytic effect Effects 0.000 abstract description 3
- 230000009089 cytolysis Effects 0.000 description 16
- 239000000203 mixture Substances 0.000 description 13
- 108010051456 Plasminogen Proteins 0.000 description 12
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 11
- 102000013566 Plasminogen Human genes 0.000 description 11
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 10
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 10
- 229920000669 heparin Polymers 0.000 description 10
- 229960002897 heparin Drugs 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 229960005356 urokinase Drugs 0.000 description 9
- 208000007536 Thrombosis Diseases 0.000 description 5
- 108010088842 Fibrinolysin Proteins 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 229940012957 plasmin Drugs 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000020764 fibrinolysis Effects 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229940059329 chondroitin sulfate Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- -1 5000 IU of heparin Chemical compound 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 206010034576 Peripheral ischaemia Diseases 0.000 description 1
- 229940122791 Plasmin inhibitor Drugs 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000002586 coronary angiography Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000014666 liquid concentrate Nutrition 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002806 plasmin inhibitor Substances 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878721951A GB8721951D0 (en) | 1987-09-18 | 1987-09-18 | Organic compounds |
| GB8721951 | 1987-09-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0283335A JPH0283335A (ja) | 1990-03-23 |
| JP2820699B2 true JP2820699B2 (ja) | 1998-11-05 |
Family
ID=10623981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63233362A Expired - Fee Related JP2820699B2 (ja) | 1987-09-18 | 1988-09-16 | 血栓溶解剤 |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0307847B1 (OSRAM) |
| JP (1) | JP2820699B2 (OSRAM) |
| AT (1) | ATE82860T1 (OSRAM) |
| AU (1) | AU623347B2 (OSRAM) |
| CA (1) | CA1337046C (OSRAM) |
| DE (1) | DE3876348T2 (OSRAM) |
| DK (1) | DK518788A (OSRAM) |
| ES (1) | ES2053658T3 (OSRAM) |
| GB (1) | GB8721951D0 (OSRAM) |
| GR (1) | GR3007194T3 (OSRAM) |
| NZ (1) | NZ226217A (OSRAM) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2764264B2 (ja) * | 1987-10-01 | 1998-06-11 | 株式会社ミドリ十字 | 線溶活性増強剤 |
| AT402367B (de) * | 1990-10-11 | 1997-04-25 | Immuno Ag | Pharmazeutische zubereitung auf basis von lys-plasminogen |
| AT402263B (de) * | 1991-06-20 | 1997-03-25 | Immuno Ag | Pharmazeutische präparation enthaltend eine thrombolytisch wirkende substanz |
| WO1994001128A1 (en) * | 1992-07-01 | 1994-01-20 | Beth Israel Hospital Boston | Enhancement of thrombolytic therapy with deglycosylated plasminogen |
| DE4320294A1 (de) * | 1993-06-18 | 1994-12-22 | Immuno Ag | Verwendung von humanem Protein C zur Verhinderung und Behandlung von Thrombozytenablagerungen |
| DE4411143C2 (de) * | 1994-03-30 | 1996-08-01 | Immuno Ag | Thrombosemittel |
| US7202066B2 (en) | 2002-01-29 | 2007-04-10 | Carrington Laboratories, Inc. | Combination of a growth factor and a protease enzyme |
| DK3391902T5 (da) * | 2015-12-18 | 2024-09-23 | Talengen Int Ltd | Plasminogen til anvendelse i behandlingen af diabetisk angiokardiopati |
| CN106890318A (zh) * | 2015-12-18 | 2017-06-27 | 深圳瑞健生命科学研究院有限公司 | 一种预防和治疗糖尿病性心脏病的新方法 |
| JP7213553B2 (ja) | 2016-12-15 | 2023-01-27 | タレンゲン インターナショナル リミテッド | 肺の繊維化を予防及び治療するための方法 |
| JP7175270B2 (ja) | 2016-12-15 | 2022-11-18 | タレンゲン インターナショナル リミテッド | グルカゴン、インスリンを正常なバランスに戻らせる方法 |
| US11207387B2 (en) | 2016-12-15 | 2021-12-28 | Talengen International Limited | Method and drug for preventing and treating obesity |
| TW202123963A (zh) | 2016-12-15 | 2021-07-01 | 大陸商深圳瑞健生命科學研究院有限公司 | 一種治療冠狀動脈粥樣硬化及其併發症的方法 |
| WO2018107707A1 (zh) * | 2016-12-15 | 2018-06-21 | 深圳瑞健生命科学研究院有限公司 | 一种改善心脏病变的方法 |
| JP7335609B2 (ja) | 2017-06-19 | 2023-08-30 | タレンゲン インターナショナル リミテッド | Ｇｌｐ－１／ｇｌｐ－１ｒを調節制御する方法および薬剤 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2504921A1 (fr) * | 1981-04-30 | 1982-11-05 | Choay Sa | Medicament nouveau constitue par un complexe aprotinine-plasmine et procede de preparation de ce nouveau complexe |
| IL80166A0 (en) * | 1985-10-01 | 1986-12-31 | American Home Prod | Method of enhancing t-pa and scu-pa production |
-
1987
- 1987-09-18 GB GB878721951A patent/GB8721951D0/en active Pending
-
1988
- 1988-09-13 ES ES88114903T patent/ES2053658T3/es not_active Expired - Lifetime
- 1988-09-13 AT AT88114903T patent/ATE82860T1/de not_active IP Right Cessation
- 1988-09-13 DE DE8888114903T patent/DE3876348T2/de not_active Expired - Fee Related
- 1988-09-13 EP EP88114903A patent/EP0307847B1/en not_active Expired - Lifetime
- 1988-09-16 JP JP63233362A patent/JP2820699B2/ja not_active Expired - Fee Related
- 1988-09-16 DK DK518788A patent/DK518788A/da not_active Application Discontinuation
- 1988-09-16 CA CA000577696A patent/CA1337046C/en not_active Expired - Fee Related
- 1988-09-16 NZ NZ226217A patent/NZ226217A/en unknown
- 1988-09-19 AU AU22400/88A patent/AU623347B2/en not_active Ceased
-
1993
- 1993-03-02 GR GR930400439T patent/GR3007194T3/el unknown
Non-Patent Citations (2)
| Title |
|---|
| Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｂｉｏｌｏｇｉｃａｌ Ｃｈｅｍｉｓｔｒｙ，Ｖｏｌ．２６１，Ｎｏ．３（１９８６）ｐ．１２５３−１２５８ |
| ＴＨＲＯＭＢＯＳＩＳ ＲＥＳＥＡＲＣＨ，Ｖｏｌ．４２，Ｎｏ．２（１９８６）ｐ．１８７−１９４ |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3876348T2 (de) | 1993-06-09 |
| GB8721951D0 (en) | 1987-10-28 |
| DK518788D0 (da) | 1988-09-16 |
| NZ226217A (en) | 1991-07-26 |
| EP0307847A3 (en) | 1990-03-07 |
| ATE82860T1 (de) | 1992-12-15 |
| DE3876348D1 (en) | 1993-01-14 |
| EP0307847B1 (en) | 1992-12-02 |
| DK518788A (da) | 1989-03-19 |
| AU2240088A (en) | 1989-03-23 |
| JPH0283335A (ja) | 1990-03-23 |
| AU623347B2 (en) | 1992-05-14 |
| GR3007194T3 (OSRAM) | 1993-07-30 |
| EP0307847A2 (en) | 1989-03-22 |
| ES2053658T3 (es) | 1994-08-01 |
| CA1337046C (en) | 1995-09-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |