NO316584B1 - Kombinasjon av trombolytisk aktive proteiner og antikoagulanter samt anvendelse derav - Google Patents
Kombinasjon av trombolytisk aktive proteiner og antikoagulanter samt anvendelse derav Download PDFInfo
- Publication number
- NO316584B1 NO316584B1 NO19964007A NO964007A NO316584B1 NO 316584 B1 NO316584 B1 NO 316584B1 NO 19964007 A NO19964007 A NO 19964007A NO 964007 A NO964007 A NO 964007A NO 316584 B1 NO316584 B1 NO 316584B1
- Authority
- NO
- Norway
- Prior art keywords
- anticoagulant
- active protein
- heparin
- thrombolytically active
- bolus injection
- Prior art date
Links
- 239000003146 anticoagulant agent Substances 0.000 title claims description 115
- 102000004169 proteins and genes Human genes 0.000 title claims description 89
- 108090000623 proteins and genes Proteins 0.000 title claims description 89
- 229940127219 anticoagulant drug Drugs 0.000 title claims description 87
- 238000001990 intravenous administration Methods 0.000 claims description 97
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical group C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 claims description 93
- 238000002347 injection Methods 0.000 claims description 93
- 239000007924 injection Substances 0.000 claims description 93
- 108010007267 Hirudins Proteins 0.000 claims description 92
- 102000007625 Hirudins Human genes 0.000 claims description 92
- 229940006607 hirudin Drugs 0.000 claims description 92
- 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 claims description 81
- 229960002897 heparin Drugs 0.000 claims description 81
- 229920000669 heparin Polymers 0.000 claims description 81
- 208000032843 Hemorrhage Diseases 0.000 claims description 40
- 208000034158 bleeding Diseases 0.000 claims description 40
- 230000000740 bleeding effect Effects 0.000 claims description 40
- 230000002537 thrombolytic effect Effects 0.000 claims description 35
- 238000011282 treatment Methods 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 25
- 108010051412 reteplase Proteins 0.000 claims description 24
- 238000002560 therapeutic procedure Methods 0.000 claims description 23
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 22
- 108010023197 Streptokinase Proteins 0.000 claims description 12
- 108010055460 bivalirudin Proteins 0.000 claims description 12
- 229960005202 streptokinase Drugs 0.000 claims description 12
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 claims description 11
- 229960001500 bivalirudin Drugs 0.000 claims description 11
- 238000009512 pharmaceutical packaging Methods 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 8
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 claims description 7
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 6
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 108010073863 saruplase Proteins 0.000 claims description 6
- 229960005356 urokinase Drugs 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 102000001938 Plasminogen Activators Human genes 0.000 claims description 4
- 108010001014 Plasminogen Activators Proteins 0.000 claims description 4
- 229940127126 plasminogen activator Drugs 0.000 claims description 4
- 238000001802 infusion Methods 0.000 description 65
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 55
- 229960001138 acetylsalicylic acid Drugs 0.000 description 42
- 208000007536 Thrombosis Diseases 0.000 description 26
- 230000004087 circulation Effects 0.000 description 25
- 239000003112 inhibitor Substances 0.000 description 23
- 206010038563 Reocclusion Diseases 0.000 description 22
- 241000282472 Canis lupus familiaris Species 0.000 description 16
- 108090000765 processed proteins & peptides Proteins 0.000 description 16
- 230000010410 reperfusion Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 230000015271 coagulation Effects 0.000 description 13
- 238000005345 coagulation Methods 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- 230000017531 blood circulation Effects 0.000 description 12
- 108050006955 Tissue-type plasminogen activator Proteins 0.000 description 10
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 108010000499 Thromboplastin Proteins 0.000 description 9
- 102000002262 Thromboplastin Human genes 0.000 description 9
- 210000004351 coronary vessel Anatomy 0.000 description 9
- 239000003527 fibrinolytic agent Substances 0.000 description 9
- 229960000103 thrombolytic agent Drugs 0.000 description 9
- 229940127218 antiplatelet drug Drugs 0.000 description 8
- 206010000891 acute myocardial infarction Diseases 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 238000004806 packaging method and process Methods 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 230000002035 prolonged effect Effects 0.000 description 7
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)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)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 6
- 206010011091 Coronary artery thrombosis Diseases 0.000 description 6
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 6
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 208000002528 coronary thrombosis Diseases 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 108010074860 Factor Xa Proteins 0.000 description 5
- 108090000190 Thrombin Proteins 0.000 description 5
- 150000001413 amino acids Chemical group 0.000 description 5
- 230000010100 anticoagulation Effects 0.000 description 5
- 210000001367 artery Anatomy 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 229960004072 thrombin Drugs 0.000 description 5
- 210000001772 blood platelet Anatomy 0.000 description 4
- 150000005829 chemical entities Chemical class 0.000 description 4
- 108010073652 desirudin Proteins 0.000 description 4
- XYWBJDRHGNULKG-OUMQNGNKSA-N desirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 XYWBJDRHGNULKG-OUMQNGNKSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 206010061216 Infarction Diseases 0.000 description 3
- 108010035030 Platelet Membrane Glycoprotein IIb Proteins 0.000 description 3
- 101800004937 Protein C Proteins 0.000 description 3
- 102000017975 Protein C Human genes 0.000 description 3
- 101800001700 Saposin-D Proteins 0.000 description 3
- 102000012607 Thrombomodulin Human genes 0.000 description 3
- 108010079274 Thrombomodulin Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000007574 infarction Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000008177 pharmaceutical agent Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 229960000856 protein c Drugs 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000003868 thrombin inhibitor Substances 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 2
- 206010051055 Deep vein thrombosis Diseases 0.000 description 2
- 241000288900 Desmodus rotundus Species 0.000 description 2
- 229940123900 Direct thrombin inhibitor Drugs 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108010045766 Platelet Glycoprotein GPIb-IX Complex Proteins 0.000 description 2
- 102000023159 Platelet Glycoprotein GPIb-IX Complex Human genes 0.000 description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 206010047249 Venous thrombosis Diseases 0.000 description 2
- 229960003318 alteplase Drugs 0.000 description 2
- 229940127090 anticoagulant agent Drugs 0.000 description 2
- 208000021328 arterial occlusion Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 108010078659 efegatran Proteins 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000000644 isotonic solution Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 108010039231 polyethyleneglycol-hirudin Proteins 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001732 thrombotic effect Effects 0.000 description 2
- 230000036964 tight binding Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000002861 ventricular Effects 0.000 description 2
- 229960001134 von willebrand factor Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KXNPVXPOPUZYGB-IOVMHBDKSA-N (2R,4R)-1-[(2S)-5-(diaminomethylideneamino)-2-[(3-methyl-1,2,3,4-tetrahydroquinolin-8-yl)sulfonylamino]-1-oxopentyl]-4-methyl-2-piperidinecarboxylic acid Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NCC(C)C2 KXNPVXPOPUZYGB-IOVMHBDKSA-N 0.000 description 1
- NIOKQPJRXDRREF-QMMMGPOBSA-N (2s)-2-amino-3-(3-carbamimidoylphenyl)propanoic acid Chemical class OC(=O)[C@@H](N)CC1=CC=CC(C(N)=N)=C1 NIOKQPJRXDRREF-QMMMGPOBSA-N 0.000 description 1
- LJCBAPRMNYSDOP-LVCYMWGESA-N (2s)-3-(7-carbamimidoylnaphthalen-2-yl)-2-[4-[(3s)-1-ethanimidoylpyrrolidin-3-yl]oxyphenyl]propanoic acid;hydron;chloride;pentahydrate Chemical compound O.O.O.O.O.Cl.C1N(C(=N)C)CC[C@@H]1OC1=CC=C([C@H](CC=2C=C3C=C(C=CC3=CC=2)C(N)=N)C(O)=O)C=C1 LJCBAPRMNYSDOP-LVCYMWGESA-N 0.000 description 1
- BISKEOIROPAOGY-RXQQAGQTSA-N (2s)-n-[(2s)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2r)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide;sulfuric acid Chemical compound OS(O)(=O)=O.C([C@@H](NC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C=O)C1=CC=CC=C1 BISKEOIROPAOGY-RXQQAGQTSA-N 0.000 description 1
- WZFJXIKSGKCGRW-XUXIUFHCSA-N 2-[(4r,7s,13s,16r)-16-acetamido-4-carbamoyl-13-[3-(diaminomethylideneamino)propyl]-14-methyl-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetrazacycloheptadec-7-yl]acetic acid Chemical compound CN1[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(N)=O)CSSC[C@H](NC(C)=O)C1=O WZFJXIKSGKCGRW-XUXIUFHCSA-N 0.000 description 1
- CSRWGJAILKTYLJ-PWGAQZMISA-N 2-[(5s,11s,14r)-11-[3-(diaminomethylideneamino)propyl]-14-ethyl-12-methyl-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentazabicyclo[15.3.1]henicosa-1(21),17,19-trien-5-yl]acetic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N(C)C(=O)[C@@H](CC)NC(=O)C2=CC=CC1=C2 CSRWGJAILKTYLJ-PWGAQZMISA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- FXFYPTZERULUBS-SQNIBIBYSA-N Ac-(D)Phe-Pro-boroArg-OH Chemical compound C([C@@H](NC(=O)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)B(O)O)C1=CC=CC=C1 FXFYPTZERULUBS-SQNIBIBYSA-N 0.000 description 1
- 108010058207 Anistreplase Proteins 0.000 description 1
- 101710163968 Antistasin Proteins 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 108010042203 D-K2P Proteins 0.000 description 1
- 108010046211 DMP 728 Proteins 0.000 description 1
- 241000288921 Desmodus Species 0.000 description 1
- 108010056764 Eptifibatide Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010048049 Factor IXa Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108010039451 LY 210825 Proteins 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010046823 MK 0852 Proteins 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 108010010336 Platelet Membrane Glycoproteins Proteins 0.000 description 1
- 102000015795 Platelet Membrane Glycoproteins Human genes 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010093860 Ro 43-5054 Proteins 0.000 description 1
- 108010079763 SDZ 217766 Proteins 0.000 description 1
- 108010021634 SK&F 106760 Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 108010064484 Silteplase Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 229940122388 Thrombin inhibitor Drugs 0.000 description 1
- 108010075065 acetylphenylalanyl-prolyl-boroarginine Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000011360 adjunctive therapy Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229960000983 anistreplase Drugs 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- -1 antibodies Proteins 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 1
- 229960003856 argatroban Drugs 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000005178 buccal mucosa Anatomy 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000011833 dog model Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- CZKPOZZJODAYPZ-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CNC2=CC=CC=C12 CZKPOZZJODAYPZ-LROMGURASA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 108010010968 hirudin HV2 Proteins 0.000 description 1
- 108010025598 hirulog-like peptide Proteins 0.000 description 1
- 102000047823 human PLAT Human genes 0.000 description 1
- 230000000544 hyperemic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 108010051044 lanoteplase Proteins 0.000 description 1
- 108010002230 lepirudin Proteins 0.000 description 1
- FIBJDTSHOUXTKV-BRHMIFOHSA-N lepirudin Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)CNC2=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O FIBJDTSHOUXTKV-BRHMIFOHSA-N 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000003055 low molecular weight heparin Substances 0.000 description 1
- 229940127215 low-molecular weight heparin Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 102000014187 peptide receptors Human genes 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229950001393 silteplase Drugs 0.000 description 1
- ALPWRKFXEOAUDR-GKEJWYBXSA-M sodium;[(2r)-2,3-di(octadecanoyloxy)propyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)([O-])=O)OC(=O)CCCCCCCCCCCCCCCCC ALPWRKFXEOAUDR-GKEJWYBXSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000008215 water for injection Substances 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
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
- A61K38/58—Protease inhibitors from animals; from humans from leeches, e.g. hirudin, eglin
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Zoology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/217,618 US5510330A (en) | 1994-03-25 | 1994-03-25 | Combinations of thrombolytically active proteins and non-heparin anticoagulants, and uses thereof. |
| PCT/EP1995/001061 WO1995026202A1 (fr) | 1994-03-25 | 1995-03-22 | Combinaisons de proteines et d'anticoagulants actifs sur le plan thrombolytique, et leurs utilisations |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO964007D0 NO964007D0 (no) | 1996-09-24 |
| NO964007L NO964007L (no) | 1996-11-25 |
| NO316584B1 true NO316584B1 (no) | 2004-03-01 |
Family
ID=22811809
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19964007A NO316584B1 (no) | 1994-03-25 | 1996-09-24 | Kombinasjon av trombolytisk aktive proteiner og antikoagulanter samt anvendelse derav |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US5510330A (fr) |
| EP (2) | EP0850648A3 (fr) |
| JP (1) | JPH09510439A (fr) |
| KR (1) | KR100366982B1 (fr) |
| CN (1) | CN1090029C (fr) |
| AT (1) | ATE167631T1 (fr) |
| AU (1) | AU702470B2 (fr) |
| BR (1) | BR9507189A (fr) |
| CA (1) | CA2186390A1 (fr) |
| CZ (1) | CZ279596A3 (fr) |
| DE (1) | DE69503120T3 (fr) |
| DK (1) | DK0751785T4 (fr) |
| ES (1) | ES2119411T5 (fr) |
| FI (1) | FI120182B (fr) |
| MX (1) | MX9603925A (fr) |
| NO (1) | NO316584B1 (fr) |
| NZ (1) | NZ282417A (fr) |
| PL (1) | PL182165B1 (fr) |
| RU (1) | RU2166326C2 (fr) |
| UA (1) | UA41398C2 (fr) |
| WO (1) | WO1995026202A1 (fr) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7846202B2 (en) | 1995-06-07 | 2010-12-07 | Cook Incorporated | Coated implantable medical device |
| US7867275B2 (en) * | 1995-06-07 | 2011-01-11 | Cook Incorporated | Coated implantable medical device method |
| US7896914B2 (en) * | 1995-06-07 | 2011-03-01 | Cook Incorporated | Coated implantable medical device |
| US7550005B2 (en) * | 1995-06-07 | 2009-06-23 | Cook Incorporated | Coated implantable medical device |
| US7611533B2 (en) * | 1995-06-07 | 2009-11-03 | Cook Incorporated | Coated implantable medical device |
| US20070203520A1 (en) * | 1995-06-07 | 2007-08-30 | Dennis Griffin | Endovascular filter |
| US6774278B1 (en) * | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
| US5840733A (en) * | 1996-07-01 | 1998-11-24 | Redcell, Canada, Inc. | Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes |
| US6010911A (en) * | 1997-04-30 | 2000-01-04 | Medtronic, Inc. | Apparatus for performing a heparin-independent high sensitivity platelet function evaluation technique |
| US6750201B1 (en) * | 1997-10-17 | 2004-06-15 | The Trustees Of The University Of Pennsylvania | Compositions and methods for promoting internalization and degradation of urokinase-type plasminogen activator |
| US6517814B2 (en) | 2001-01-09 | 2003-02-11 | Bristol-Myers Squibb Pharma Company | Macrocyclic chelants useful for metallopharmaceuticals |
| DE10115740A1 (de) * | 2001-03-26 | 2002-10-02 | Ulrich Speck | Zubereitung für die Restenoseprophylaxe |
| DE10153601A1 (de) * | 2001-11-02 | 2003-05-22 | Paion Gmbh | DSPA zur Behandlung von Schlaganfall |
| FI20020197A0 (fi) * | 2002-02-01 | 2002-02-01 | Orion Corp | Yhdistelmä akuutin myokardiilisen infarktin hoitoon |
| US7084118B2 (en) * | 2002-02-22 | 2006-08-01 | Genentech, Inc. | Combination treatment with t-PA variant and low molecular weight heparin |
| EP1521603B1 (fr) * | 2002-07-12 | 2011-01-19 | Cook Incorporated | Dispositif medical muni d'un revetement |
| DE10244847A1 (de) * | 2002-09-20 | 2004-04-01 | Ulrich Prof. Dr. Speck | Medizinische Vorrichtung zur Arzneimittelabgabe |
| WO2005116623A2 (fr) | 2004-05-17 | 2005-12-08 | Medtronic, Inc. | Systeme de determination de l'heparine selon les points d'intervention |
| US20060222640A1 (en) * | 2005-03-29 | 2006-10-05 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions for treatment of thrombosis |
| AR068914A1 (es) * | 2007-10-18 | 2009-12-16 | Paion Deutschland Gmbh | Uso de un activador de plasminogeno para la preparacion de un medicamento para el tratamiento de apoplejia |
| US20110027337A1 (en) * | 2007-12-21 | 2011-02-03 | Ifxa A/S | Protease inhibitor |
| WO2016073514A2 (fr) | 2014-11-03 | 2016-05-12 | Thrombolytic Science, Llc | Méthodes et compositions pour thrombolyse sûre et efficace |
| WO2016122288A2 (fr) * | 2015-01-30 | 2016-08-04 | 고려대학교산학협력단 | Formulation combinée comprenant un dérivé de verbénone et un agent thérapeutique pour une reperfusion pour la prévention ou le traitement de maladies cérébrovasculaires, de l'artériosclérose ou de maladies cardio-vasculaires |
| RU2622006C2 (ru) * | 2015-06-15 | 2017-06-08 | Федеральное государственное автономное образовательное учреждение высшего профессионального образования "Казанский (Приволжский) федеральный университет" (ФГАОУВПО КФУ) | Применение рекомбинантного штамма bacillus subtilis eo-11 вкпм в-11978 в качестве продуцента субтилизиноподобной протеиназы, вещества с тромболитическими и антикоагулянтными свойствами |
| CN105396127A (zh) * | 2015-11-13 | 2016-03-16 | 中国人民解放军第四军医大学 | 一种用于急性心肌梗死的冠状动脉溶栓剂 |
| WO2018232305A1 (fr) * | 2017-06-16 | 2018-12-20 | Thrombolytic Science, Llc | Procédés et compositions pour la thrombolyse |
| CN117534731A (zh) * | 2021-09-24 | 2024-02-09 | 江西康之康中药科技有限公司 | 一种抗凝血肽及其在抗凝血产品上的应用 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8508717D0 (en) * | 1985-04-03 | 1985-05-09 | Beecham Group Plc | Composition |
| DK43387A (da) † | 1986-01-29 | 1987-07-30 | Beecham Group Plc | Fibrinolytisk enzym |
| US5084274A (en) * | 1987-11-17 | 1992-01-28 | Scripps Clinic And Research Foundation | Inhibition of arterial thrombotic occlusion or thromboembolism |
| DE3804600A1 (de) * | 1988-02-13 | 1989-08-24 | Basf Ag | Mischung aus einer thrombolytisch wirkenden und einer antithrombotischen substanz |
| GB8822147D0 (en) * | 1988-09-21 | 1988-10-26 | Ciba Geigy Ag | Pharmaceutically active combination |
| US5204323B1 (en) * | 1988-10-06 | 1995-07-18 | Ciba Geigy Corp | Hirudin antidotal compositions and methods |
| GB8826428D0 (en) * | 1988-11-11 | 1988-12-14 | Biopharm Ltd | Antithrombin |
| US4980165A (en) * | 1989-01-27 | 1990-12-25 | Genetics Institute, Inc. | Pharmaceutical formulations of plasminogen activator proteins |
| DE3903581A1 (de) * | 1989-02-07 | 1990-08-16 | Boehringer Mannheim Gmbh | Gewebs-plasminogenaktivator-derivat |
| CA2064231A1 (fr) * | 1989-07-20 | 1991-01-21 | John M. Maraganore | Combinaisons et methodes pour le traitement ou la prevention des maladies dues a des thromboses |
| US5196404B1 (en) * | 1989-08-18 | 1996-09-10 | Biogen Inc | Inhibitors of thrombin |
| US5240913A (en) * | 1989-08-18 | 1993-08-31 | Biogen, Inc. | Inhibitors of thrombin |
| US5049132A (en) * | 1990-01-08 | 1991-09-17 | Cordis Corporation | Balloon catheter for delivering therapeutic agents |
| US5189019A (en) * | 1990-04-23 | 1993-02-23 | Merck & Co., Inc. | Antistasin derived anticoagulant protein |
| US5242810A (en) * | 1990-12-07 | 1993-09-07 | Biogen, Inc. | Bifunctional inhibitors of thrombin and platelet activation |
| US5242688A (en) * | 1990-12-24 | 1993-09-07 | Eli Lilly And Company | Method of treating thromboembolic disorders by administration of diglycosylated t-pa variants |
| ES2082465T3 (es) † | 1991-04-16 | 1996-03-16 | Boehringer Mannheim Gmbh | Unidad farmaceutica de envasado que contiene activadores de plasminogeno para la administracion multiple de bolos. |
| AU664469B2 (en) † | 1992-06-03 | 1995-11-16 | Genentech Inc. | Tissue plasminogen activator glycosylation variants with improved therapeutic properties |
-
1994
- 1994-03-25 US US08/217,618 patent/US5510330A/en not_active Expired - Lifetime
-
1995
- 1995-03-22 NZ NZ282417A patent/NZ282417A/en not_active IP Right Cessation
- 1995-03-22 BR BR9507189A patent/BR9507189A/pt not_active Application Discontinuation
- 1995-03-22 MX MX9603925A patent/MX9603925A/es not_active IP Right Cessation
- 1995-03-22 CN CN95192275A patent/CN1090029C/zh not_active Expired - Fee Related
- 1995-03-22 PL PL95316449A patent/PL182165B1/pl not_active IP Right Cessation
- 1995-03-22 WO PCT/EP1995/001061 patent/WO1995026202A1/fr not_active Application Discontinuation
- 1995-03-22 KR KR1019960705381A patent/KR100366982B1/ko not_active IP Right Cessation
- 1995-03-22 DK DK95912261T patent/DK0751785T4/da active
- 1995-03-22 DE DE69503120T patent/DE69503120T3/de not_active Expired - Lifetime
- 1995-03-22 ES ES95912261T patent/ES2119411T5/es not_active Expired - Lifetime
- 1995-03-22 RU RU96119944/14A patent/RU2166326C2/ru not_active IP Right Cessation
- 1995-03-22 UA UA96104031A patent/UA41398C2/uk unknown
- 1995-03-22 CA CA002186390A patent/CA2186390A1/fr not_active Abandoned
- 1995-03-22 AT AT95912261T patent/ATE167631T1/de active
- 1995-03-22 EP EP98102473A patent/EP0850648A3/fr not_active Ceased
- 1995-03-22 EP EP95912261A patent/EP0751785B2/fr not_active Expired - Lifetime
- 1995-03-22 CZ CZ962795A patent/CZ279596A3/cs unknown
- 1995-03-22 JP JP7519775A patent/JPH09510439A/ja active Pending
- 1995-03-22 AU AU19511/95A patent/AU702470B2/en not_active Ceased
-
1996
- 1996-09-24 FI FI963802A patent/FI120182B/fi not_active IP Right Cessation
- 1996-09-24 NO NO19964007A patent/NO316584B1/no not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO316584B1 (no) | Kombinasjon av trombolytisk aktive proteiner og antikoagulanter samt anvendelse derav | |
| US5759542A (en) | Compositions and methods for the delivery of drugs by platelets for the treatment of cardiovascular and other diseases | |
| EP0307847B1 (fr) | Agent thrombolytique | |
| WO2012060607A2 (fr) | Composition pour la dissolution de thrombi, et composition pharmaceutique pour le traitement de maladies vasculaires sténotiques ou occlusives qui la comprend | |
| US20200172574A1 (en) | Inhibition of cardiac fibrosis in myocardial infarction | |
| CA2064231A1 (fr) | Combinaisons et methodes pour le traitement ou la prevention des maladies dues a des thromboses | |
| Müller et al. | Pharmacology of current and future antithrombotic therapies | |
| Bode et al. | New developments in thrombolytic therapy | |
| CA2024309C (fr) | Compositions pharmaceutiques comprenant des activateurs de plasminogene modifies et non-modifies et leurs utilisations | |
| Jang et al. | A randomized, blinded study of two doses of Novastan®(brand of argatroban) versus heparin as adjunctive therapy to recombinant tissue plasminogen activator (accelerated administration) in acute myocardial infarction: Rationale and design of the Myocardial Infarction using Novastan® and t-PA (MINT) study | |
| WO1992018139A1 (fr) | Molecules chimeriques ayant une activite d'activation de plasminogene et affinite pour les plaques atherosclerotiques | |
| Agnelli | Thrombolytic and antithrombotic treatment in myocardial infarction: main achievements and future perspectives | |
| Scharfstein et al. | Molecular approaches to antithrombotic therapy | |
| US7271143B1 (en) | Peptides for regulation of urokinase (uPA) and tissue type (tPA) plasminogen activator and method of optimizing therapeutic efficacy | |
| Verstraete | Thrombolysis: an approach still on the move | |
| US20200054719A1 (en) | E-we thrombin analog and fibrinolytic combination | |
| WO2003095476A2 (fr) | Peptides regulant les activateurs du plasminogene de l'urokinase (upa) et du type de tissu (tpa) et procede d'optimisation de l'efficacite therapeutique | |
| Agnelli | New strategies for enhancing the speed and rate of coronary reperfusion | |
| Becker et al. | Evolution of direct thrombin antagonists: acknowledging potential limitations | |
| Schneider et al. | Acute coronary syndromes: 2. Antiplatelet agents | |
| Rapaport | Thrombolytic therapy for myocardial ischemia and infarction | |
| Meidell | After GUSTO and PAMI: directions in management of acute coronary ischemia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| CREP | Change of representative |
Representative=s name: ZACCO NORWAY AS, POSTBOKS 2003 VIKA |
|
| MM1K | Lapsed by not paying the annual fees |