RU2514878C2 - Предотвращение образования и/или стабилизации тромбов - Google Patents
Предотвращение образования и/или стабилизации тромбов Download PDFInfo
- Publication number
- RU2514878C2 RU2514878C2 RU2007123797/14A RU2007123797A RU2514878C2 RU 2514878 C2 RU2514878 C2 RU 2514878C2 RU 2007123797/14 A RU2007123797/14 A RU 2007123797/14A RU 2007123797 A RU2007123797 A RU 2007123797A RU 2514878 C2 RU2514878 C2 RU 2514878C2
- Authority
- RU
- Russia
- Prior art keywords
- fxii
- mice
- formation
- blood
- antibody
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 71
- 230000006641 stabilisation Effects 0.000 title claims abstract description 12
- 230000002265 prevention Effects 0.000 title claims abstract description 5
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 88
- 108010080865 Factor XII Proteins 0.000 claims abstract description 28
- 102000000429 Factor XII Human genes 0.000 claims abstract description 28
- 230000023597 hemostasis Effects 0.000 claims abstract description 13
- 230000001575 pathological effect Effects 0.000 claims abstract description 10
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 230000012010 growth Effects 0.000 claims abstract description 6
- 230000004913 activation Effects 0.000 claims description 23
- 239000003112 inhibitor Substances 0.000 claims description 22
- 238000011105 stabilization Methods 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 115
- 230000006378 damage Effects 0.000 description 40
- 230000015271 coagulation Effects 0.000 description 32
- 238000005345 coagulation Methods 0.000 description 32
- 229920001436 collagen Polymers 0.000 description 32
- 102000008186 Collagen Human genes 0.000 description 31
- 108010035532 Collagen Proteins 0.000 description 31
- 210000002381 plasma Anatomy 0.000 description 27
- 230000007812 deficiency Effects 0.000 description 25
- 230000037361 pathway Effects 0.000 description 23
- 238000001727 in vivo Methods 0.000 description 20
- 230000023555 blood coagulation Effects 0.000 description 18
- 230000035602 clotting Effects 0.000 description 18
- 208000032843 Hemorrhage Diseases 0.000 description 17
- 208000034158 bleeding Diseases 0.000 description 17
- 230000000740 bleeding effect Effects 0.000 description 17
- 210000004369 blood Anatomy 0.000 description 16
- 239000008280 blood Substances 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- 108090000190 Thrombin Proteins 0.000 description 15
- 229960004072 thrombin Drugs 0.000 description 15
- 108010000499 Thromboplastin Proteins 0.000 description 14
- 102000002262 Thromboplastin Human genes 0.000 description 14
- 230000002950 deficient Effects 0.000 description 14
- 230000003902 lesion Effects 0.000 description 14
- 102000009123 Fibrin Human genes 0.000 description 13
- 108010073385 Fibrin Proteins 0.000 description 13
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 13
- 229950003499 fibrin Drugs 0.000 description 13
- 241000282414 Homo sapiens Species 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 12
- 230000017531 blood circulation Effects 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 230000007547 defect Effects 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 210000002565 arteriole Anatomy 0.000 description 10
- 230000006870 function Effects 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 8
- 102100035792 Kininogen-1 Human genes 0.000 description 8
- 102000003827 Plasma Kallikrein Human genes 0.000 description 8
- 108090000113 Plasma Kallikrein Proteins 0.000 description 8
- 239000003146 anticoagulant agent Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 210000001715 carotid artery Anatomy 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 230000010118 platelet activation Effects 0.000 description 7
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 6
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 6
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 6
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 210000000709 aorta Anatomy 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 5
- 229930182837 (R)-adrenaline Natural products 0.000 description 5
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 5
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 5
- 239000005995 Aluminium silicate Substances 0.000 description 5
- 201000007176 Factor XII Deficiency Diseases 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 102100038394 Platelet glycoprotein VI Human genes 0.000 description 5
- 101710194982 Platelet glycoprotein VI Proteins 0.000 description 5
- 235000012211 aluminium silicate Nutrition 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229960005139 epinephrine Drugs 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 230000002947 procoagulating effect Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- -1 sulfatides Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- 230000003966 vascular damage Effects 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 102100023804 Coagulation factor VII Human genes 0.000 description 4
- 108010048623 Collagen Receptors Proteins 0.000 description 4
- 108010023321 Factor VII Proteins 0.000 description 4
- 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 4
- 241001468926 Limanda aspera Species 0.000 description 4
- 206010047249 Venous thrombosis Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 239000012190 activator Substances 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 230000002785 anti-thrombosis Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 229940012413 factor vii Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229920000669 heparin Polymers 0.000 description 4
- 229960002897 heparin Drugs 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000007928 intraperitoneal injection Substances 0.000 description 4
- 238000012771 intravital microscopy Methods 0.000 description 4
- 210000003975 mesenteric artery Anatomy 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 210000004623 platelet-rich plasma Anatomy 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 108010039627 Aprotinin Proteins 0.000 description 3
- 206010003178 Arterial thrombosis Diseases 0.000 description 3
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 206010053567 Coagulopathies Diseases 0.000 description 3
- 208000005189 Embolism Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000000507 Integrin alpha2 Human genes 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 description 3
- 208000001435 Thromboembolism Diseases 0.000 description 3
- 108010059382 Zea mays trypsin inhibitor Proteins 0.000 description 3
- 229940127219 anticoagulant drug Drugs 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 230000020764 fibrinolysis Effects 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 238000000799 fluorescence microscopy Methods 0.000 description 3
- 230000002008 hemorrhagic effect Effects 0.000 description 3
- 230000002439 hemostatic effect Effects 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 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 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 2
- 108010087765 Antipain Proteins 0.000 description 2
- 102000007347 Apyrase Human genes 0.000 description 2
- 108010007730 Apyrase Proteins 0.000 description 2
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 2
- 102100022641 Coagulation factor IX Human genes 0.000 description 2
- 102000055157 Complement C1 Inhibitor Human genes 0.000 description 2
- 108700040183 Complement C1 Inhibitor Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 101710194146 Ecotin Proteins 0.000 description 2
- 206010014513 Embolism arterial Diseases 0.000 description 2
- 206010014522 Embolism venous Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010076282 Factor IX Proteins 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 108010017642 Integrin alpha2beta1 Proteins 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 102000002397 Kinins Human genes 0.000 description 2
- 108010093008 Kinins Proteins 0.000 description 2
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 108010094028 Prothrombin Proteins 0.000 description 2
- 102100027378 Prothrombin Human genes 0.000 description 2
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 2
- 101710112924 Trypsin inhibitor 5 Proteins 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 2
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 239000002506 anticoagulant protein Substances 0.000 description 2
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 2
- 238000002617 apheresis Methods 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001112 coagulating effect Effects 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 101150047356 dec-1 gene Proteins 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229960004222 factor ix Drugs 0.000 description 2
- 102000013373 fibrillar collagen Human genes 0.000 description 2
- 108060002894 fibrillar collagen Proteins 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 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 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 210000004731 jugular vein Anatomy 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 108010052968 leupeptin Proteins 0.000 description 2
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000004792 oxidative damage Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 210000004976 peripheral blood cell Anatomy 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 229920000447 polyanionic polymer Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003805 procoagulant Substances 0.000 description 2
- 229940039716 prothrombin Drugs 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 208000004644 retinal vein occlusion Diseases 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000009424 thromboembolic effect Effects 0.000 description 2
- 230000002885 thrombogenetic effect Effects 0.000 description 2
- 230000003558 thrombophilic effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 208000004043 venous thromboembolism Diseases 0.000 description 2
- 238000010865 video microscopy Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 2
- 229960001600 xylazine Drugs 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- HIYAVKIYRIFSCZ-CVXKHCKVSA-N Calcimycin Chemical compound CC([C@H]1OC2([C@@H](C[C@H]1C)C)O[C@H]([C@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-CVXKHCKVSA-N 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000009268 Collagen Receptors Human genes 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 208000011029 Congenital factor XII deficiency Diseases 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 229920002079 Ellagic acid Polymers 0.000 description 1
- AFSDNFLWKVMVRB-UHFFFAOYSA-N Ellagic acid Chemical compound OC1=C(O)C(OC2=O)=C3C4=C2C=C(O)C(O)=C4OC(=O)C3=C1 AFSDNFLWKVMVRB-UHFFFAOYSA-N 0.000 description 1
- ATJXMQHAMYVHRX-CPCISQLKSA-N Ellagic acid Natural products OC1=C(O)[C@H]2OC(=O)c3cc(O)c(O)c4OC(=O)C(=C1)[C@H]2c34 ATJXMQHAMYVHRX-CPCISQLKSA-N 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108010074864 Factor XI Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 101710113864 Heat shock protein 90 Proteins 0.000 description 1
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 1
- 206010019860 Hereditary angioedema Diseases 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010020608 Hypercoagulation Diseases 0.000 description 1
- 101710180643 Leishmanolysin Proteins 0.000 description 1
- 241000282342 Martes americana Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108010035766 P-Selectin Proteins 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 206010037437 Pulmonary thrombosis Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 101710162629 Trypsin inhibitor 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
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
- 108090001015 cancer procoagulant Proteins 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 108010077026 collagen-related peptide Proteins 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229960002852 ellagic acid Drugs 0.000 description 1
- 235000004132 ellagic acid Nutrition 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940089602 epinephrine injection Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 201000007219 factor XI deficiency Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 229940090044 injection Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012836 macromolecular constituent Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000008742 procoagulation Effects 0.000 description 1
- 239000003649 prolyl endopeptidase inhibitor Substances 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000003331 prothrombotic effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 201000005665 thrombophilia Diseases 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000006459 vascular development Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
-
- 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
- A61K38/556—Angiotensin converting enzyme inhibitors
-
- 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
- A61K38/56—Protease inhibitors from plants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- 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
- A61P9/10—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/36—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Botany (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Zoology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Communicable Diseases (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04030593 | 2004-12-23 | ||
| EP04030593.0 | 2004-12-23 | ||
| PCT/EP2005/013714 WO2006066878A1 (en) | 2004-12-23 | 2005-12-20 | Prevention of thrombus formation and/or stabilization |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2007123797A RU2007123797A (ru) | 2009-01-10 |
| RU2514878C2 true RU2514878C2 (ru) | 2014-05-10 |
Family
ID=34927953
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007123797/14A RU2514878C2 (ru) | 2004-12-23 | 2005-12-20 | Предотвращение образования и/или стабилизации тромбов |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US8119137B2 (enExample) |
| EP (2) | EP2272565A3 (enExample) |
| JP (1) | JP5118492B2 (enExample) |
| KR (1) | KR101277097B1 (enExample) |
| CN (1) | CN101102819A (enExample) |
| AU (1) | AU2005318464B2 (enExample) |
| BR (1) | BRPI0519349A8 (enExample) |
| CA (1) | CA2591786C (enExample) |
| DK (1) | DK1830924T3 (enExample) |
| ES (1) | ES2407965T3 (enExample) |
| MX (1) | MX2007006997A (enExample) |
| PL (1) | PL1830924T3 (enExample) |
| RU (1) | RU2514878C2 (enExample) |
| WO (1) | WO2006066878A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2817219C2 (ru) * | 2019-01-21 | 2024-04-11 | Аронора Инк. | Новые гуманизированные антитела к фактору xi с антитромботическим и противовоспалительным действием и их применение |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6057287A (en) | 1994-01-11 | 2000-05-02 | Dyax Corp. | Kallikrein-binding "Kunitz domain" proteins and analogues thereof |
| ES2528254T3 (es) | 2002-06-07 | 2015-02-05 | Dyax Corp. | Polipéptidos de dominio Kunitz modificado y su uso para reducir la isquemia o el inicio de una respuesta inflamatoria sistémica asociada con un procedimiento quirúrgico |
| US7153829B2 (en) | 2002-06-07 | 2006-12-26 | Dyax Corp. | Kallikrein-inhibitor therapies |
| DK1542710T3 (da) | 2002-08-28 | 2012-10-15 | Dyax Corp | Fremgangsmåde til konservering af organer og væv |
| US7235530B2 (en) | 2004-09-27 | 2007-06-26 | Dyax Corporation | Kallikrein inhibitors and anti-thrombolytic agents and uses thereof |
| GB0607515D0 (en) * | 2006-04-13 | 2006-05-24 | Axis Shield Diagnostics Ltd | Anti-factor xlla therapy |
| WO2008016883A2 (en) | 2006-07-31 | 2008-02-07 | Activesite Pharmaceuticals, Inc. | Inhibitors of plasma kallikrein |
| DK2526962T3 (da) * | 2007-02-12 | 2019-10-07 | Csl Behring Gmbh | Therapeutic application of Kazal-type serine protease inhibitors |
| WO2009026539A1 (en) * | 2007-08-23 | 2009-02-26 | Genzyme Corporation | Treatment with kallikrein inhibitors |
| EP2215256A1 (en) * | 2007-10-22 | 2010-08-11 | Georg Dewald | Disorders of vasoregulation and methods of diagnosing them |
| EP2103311A1 (en) | 2008-03-20 | 2009-09-23 | CSL Behring GmbH | The calcium sensor STIM1 is essential for pathological thrombus formation |
| EP2145900A1 (en) | 2008-07-15 | 2010-01-20 | CSL Behring GmbH | Orai1 (CRACM1) is the platelet SOC channel and essential for pathological thrombus formation |
| WO2010080833A1 (en) | 2009-01-06 | 2010-07-15 | Dyax Corp. | Treatment of mucositis with kallikrein inhibitors |
| EP2269597A1 (en) | 2009-06-22 | 2011-01-05 | CSL Behring GmbH | CLEC-2 is an essential platelet activating receptor in hemostasis and thrombosis |
| EP2272874A1 (en) | 2009-07-10 | 2011-01-12 | CSL Behring GmbH | Role of PLD1 in thrombus formation and integrin alpha IIb beta 3 activation |
| HRP20220107T1 (hr) | 2010-01-06 | 2022-04-15 | Takeda Pharmaceutical Company Limited | Proteini koji vežu kalikrein plazme |
| EP2371857A1 (en) * | 2010-04-01 | 2011-10-05 | CSL Behring GmbH | Factor XII inhibitors for treating interstitial lung disease |
| US9150864B2 (en) * | 2010-11-08 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Methods for modulating factor 12 expression |
| KR102107695B1 (ko) | 2011-01-06 | 2020-05-07 | 다이액스 코포레이션 | 혈장 칼리크레인 결합 단백질 |
| EP2497489A1 (en) * | 2011-03-09 | 2012-09-12 | CSL Behring GmbH | Factor XII inhibitors for the treatment of silent brain ischemia and ischemia of other organs |
| CN103415301A (zh) * | 2011-03-09 | 2013-11-27 | 德国杰特贝林生物制品有限公司 | 用于与包括与人造表面接触的医疗操作一起施用的fxii抑制剂 |
| WO2012170947A2 (en) | 2011-06-10 | 2012-12-13 | Isis Pharmaceuticals, Inc. | Methods for modulating factor 12 expression |
| EP2548892A1 (en) | 2011-07-22 | 2013-01-23 | CSL Behring GmbH | Inhibitory anti-Factor XII/XIIa monoclonal Antibodies and their uses |
| JP6253578B2 (ja) * | 2011-07-22 | 2017-12-27 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | 阻害性抗第ｘｉｉ／ｘｉｉａ因子モノクローナル抗体及びそれらの使用 |
| WO2013028069A1 (en) * | 2011-08-23 | 2013-02-28 | Synapse B.V. | Thermostable inhibitors of activation of the blood clotting system through contact with foreign surfaces. |
| EP2623110A1 (en) | 2012-01-31 | 2013-08-07 | CSL Behring GmbH | Factor XII inhibitors for the treatment of neurological inflammatory disorders |
| WO2014089493A1 (en) * | 2012-12-07 | 2014-06-12 | Vanderbilt University | Antibodies against factor xii and uses thereof |
| CA2901225C (en) | 2013-03-08 | 2023-09-19 | Csl Behring Gmbh | Treatment and prevention of remote ischemia-reperfusion injury |
| KR20160026905A (ko) * | 2013-06-28 | 2016-03-09 | 체에스엘 베링 게엠베하 | 인자 ｘｉｉ 억제제 및 ｃ1-억제제를 이용한 병용 치료요법 |
| AU2015276089B2 (en) | 2014-06-18 | 2021-03-18 | Csl Behring Gmbh | Therapy using a Factor XII inhibitor in a neurotraumatic disorder |
| US11390687B2 (en) | 2015-01-02 | 2022-07-19 | Takeda Pharmaceutical Company Limited | Bispecific antibodies against plasma kallikrein and Factor XII |
| CA2982413A1 (en) * | 2015-04-28 | 2016-11-03 | Ecole Polytechnique Federale De Lausanne (Epfl) | Novel inhibitors of the enzyme activated factor xii (fxiia) |
| AU2016297018B9 (en) | 2015-07-21 | 2022-12-01 | Takeda Pharmaceutical Company Limited | A monoclonal antibody inhibitor of factor XIIa |
| EP3387018A1 (en) | 2015-12-11 | 2018-10-17 | Dyax Corp. | Plasma kallikrein inhibitors and uses thereof for treating hereditary angioedema attack |
| EP3440107A4 (en) | 2016-04-06 | 2020-02-19 | CSL Limited | METHOD FOR TREATING ATHEROSCLEROSIS |
| AU2018382222B2 (en) | 2017-12-15 | 2025-09-04 | Csl Limited | Use of a FXIIa-inhibitor in the treatment of renal fibrosis and/or chronic kidney disease |
| CN112437682B (zh) | 2018-06-19 | 2024-11-05 | 里珍纳龙药品有限公司 | 抗因子XII/XIIa抗体和其用途 |
| US12134657B2 (en) | 2018-11-28 | 2024-11-05 | Oregon Health & Science University | Therapeutic factor XII antibody |
| BR112022000113A2 (pt) | 2019-07-08 | 2022-03-15 | Activesite Pharmaceuticals Inc | Processos para preparação de inibidores de calicreí-na de plasma |
| AU2021209045A1 (en) | 2020-01-13 | 2022-07-28 | Takeda Pharmaceutical Company Limited | Plasma kallikrein inhibitors and uses thereof for treating pediatric hereditary angioedema attack |
| US20240352150A2 (en) * | 2020-06-16 | 2024-10-24 | Ningbo Comgen Biotech Co., Ltd. | Anti-factor xii (fxii) nanobody or antigen-binding fragment thereof, and use thereof |
| CN116670280A (zh) | 2020-12-18 | 2023-08-29 | Ionis 制药公司 | 用于调节因子xii的化合物和方法 |
| AU2024291721A1 (en) | 2023-07-19 | 2026-01-22 | Regeneron Pharmaceuticals, Inc. | ANTI-FACTOR XII/XIIa ANTIBODIES AND USES THEREOF |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4963657A (en) * | 1988-06-09 | 1990-10-16 | Temple University Of The Commonwealth System Of Higher Education | Monoclonal antibodies to the light chain region of human factor XII and methods of preparing and using the same |
| RU2172321C2 (ru) * | 1996-03-01 | 2001-08-20 | Акцо Нобель Н.В. | Ингибиторы сериновых протеаз |
| EP1222929A2 (en) * | 2001-01-11 | 2002-07-17 | D. Collen Research Foundation vzw | Method and pharmaceutical composition for preventing and/or treating systemic inflammatory response syndrome |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK225488D0 (da) * | 1988-04-26 | 1988-04-26 | Novo Industri As | Polypeptid |
| WO1994020535A1 (en) | 1992-12-11 | 1994-09-15 | Corvas International, Inc. | ECOTIN AS A FACTOR Xa, XIa, AND XIIa INHIBITOR |
| CA2170030A1 (en) | 1993-09-14 | 1995-03-23 | Robert A. Lazarus | Pharmaceutical compositions containing ecotin and homologs thereof |
| ZA963619B (en) * | 1995-05-08 | 1996-11-22 | Scios Inc | Protease inhibitor peptides |
| US20030109680A1 (en) | 2001-11-21 | 2003-06-12 | Sunol Molecular Corporation | Antibodies for inhibiting blood coagulation and methods of use thereof |
| DE19725014A1 (de) * | 1997-06-13 | 1998-12-17 | Bayer Ag | Aprotininvarianten mit verbesserten Eigenschaften und Bikunine von Aprotininvarianten |
| GB9800817D0 (en) | 1998-01-16 | 1998-03-11 | Bio Discovery Ltd | Serine protease inhibitors |
| ATE274600T1 (de) * | 1998-06-08 | 2004-09-15 | Univ Vermont | Verfahren zur bestimmung der blutgerinnung in plasma |
| JP2002525298A (ja) * | 1998-09-28 | 2002-08-13 | メルク エンド カムパニー インコーポレーテッド | トロンビン阻害剤の投与による炎症疾患の処置法 |
| US7153829B2 (en) * | 2002-06-07 | 2006-12-26 | Dyax Corp. | Kallikrein-inhibitor therapies |
| ES2528254T3 (es) * | 2002-06-07 | 2015-02-05 | Dyax Corp. | Polipéptidos de dominio Kunitz modificado y su uso para reducir la isquemia o el inicio de una respuesta inflamatoria sistémica asociada con un procedimiento quirúrgico |
| WO2004004640A2 (en) | 2002-07-05 | 2004-01-15 | Tetragrammaton Inc. | Methods, compositions and kits for treating damage to excitable tissue |
| DK1542710T3 (da) * | 2002-08-28 | 2012-10-15 | Dyax Corp | Fremgangsmåde til konservering af organer og væv |
| US20040229778A1 (en) | 2003-05-13 | 2004-11-18 | Elmaleh David R. | Pharmaceutical compositions of antithrombin III for the treatment of retroviral diseases |
| WO2004110356A2 (en) | 2003-05-15 | 2004-12-23 | Cbr Institute For Biomedical Research, Inc. | Methods for modulating cell-to-cell adhesion using an agonist of c1inh-type protein activity |
| DK1626736T3 (da) | 2003-05-16 | 2020-09-28 | Pharming Intellectual Property B V | C1-inhibitor med kort halveringstid til midlertidig behandling |
| US8152750B2 (en) | 2003-09-12 | 2012-04-10 | Marine Polymer Technologies, Inc. | Vascular access preservation in hemodialysis patients |
| GB0411145D0 (en) | 2004-05-19 | 2004-06-23 | Imp College Innovations Ltd | Protease inhibitors and their therapeutic applications |
| US8569277B2 (en) | 2004-08-11 | 2013-10-29 | Palo Alto Investors | Methods of treating a subject for a condition |
| GB0418877D0 (en) | 2004-08-24 | 2004-09-29 | Univ Edinburgh | Heart |
| US20060104944A1 (en) | 2004-11-18 | 2006-05-18 | Mousa Shaker A | Activators and inhibitors of protease activated receptor2 (PAR2) and methods of use |
| SI1669074T1 (sl) | 2004-12-01 | 2010-10-29 | Par Pharmaceuticals Inc | Uporaba megestrol acetata za izboljšanje delovanja srca in zdravljenje srčnega popuščanja |
-
2005
- 2005-12-20 CN CNA2005800465756A patent/CN101102819A/zh active Pending
- 2005-12-20 BR BRPI0519349A patent/BRPI0519349A8/pt not_active Application Discontinuation
- 2005-12-20 JP JP2007547323A patent/JP5118492B2/ja not_active Expired - Lifetime
- 2005-12-20 DK DK05820601.2T patent/DK1830924T3/da active
- 2005-12-20 EP EP10183075A patent/EP2272565A3/en not_active Withdrawn
- 2005-12-20 WO PCT/EP2005/013714 patent/WO2006066878A1/en not_active Ceased
- 2005-12-20 RU RU2007123797/14A patent/RU2514878C2/ru not_active Application Discontinuation
- 2005-12-20 MX MX2007006997A patent/MX2007006997A/es active IP Right Grant
- 2005-12-20 US US11/793,820 patent/US8119137B2/en active Active
- 2005-12-20 AU AU2005318464A patent/AU2005318464B2/en not_active Expired
- 2005-12-20 CA CA2591786A patent/CA2591786C/en not_active Expired - Lifetime
- 2005-12-20 ES ES05820601T patent/ES2407965T3/es not_active Expired - Lifetime
- 2005-12-20 PL PL05820601T patent/PL1830924T3/pl unknown
- 2005-12-20 EP EP05820601A patent/EP1830924B1/en not_active Expired - Lifetime
- 2005-12-20 KR KR1020077016992A patent/KR101277097B1/ko not_active Expired - Lifetime
-
2011
- 2011-12-29 US US13/339,793 patent/US20120148688A1/en not_active Abandoned
-
2012
- 2012-12-21 US US13/723,847 patent/US8715672B2/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4963657A (en) * | 1988-06-09 | 1990-10-16 | Temple University Of The Commonwealth System Of Higher Education | Monoclonal antibodies to the light chain region of human factor XII and methods of preparing and using the same |
| RU2172321C2 (ru) * | 1996-03-01 | 2001-08-20 | Акцо Нобель Н.В. | Ингибиторы сериновых протеаз |
| EP1222929A2 (en) * | 2001-01-11 | 2002-07-17 | D. Collen Research Foundation vzw | Method and pharmaceutical composition for preventing and/or treating systemic inflammatory response syndrome |
Non-Patent Citations (1)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2817219C2 (ru) * | 2019-01-21 | 2024-04-11 | Аронора Инк. | Новые гуманизированные антитела к фактору xi с антитромботическим и противовоспалительным действием и их применение |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2407965T3 (es) | 2013-06-17 |
| US8715672B2 (en) | 2014-05-06 |
| EP2272565A2 (en) | 2011-01-12 |
| US20080254039A1 (en) | 2008-10-16 |
| DK1830924T3 (da) | 2013-05-21 |
| EP1830924A1 (en) | 2007-09-12 |
| BRPI0519349A8 (pt) | 2017-09-12 |
| WO2006066878A1 (en) | 2006-06-29 |
| KR101277097B1 (ko) | 2013-06-20 |
| RU2007123797A (ru) | 2009-01-10 |
| AU2005318464A1 (en) | 2006-06-29 |
| JP5118492B2 (ja) | 2013-01-16 |
| PL1830924T3 (pl) | 2013-08-30 |
| KR20070092303A (ko) | 2007-09-12 |
| US20120148688A1 (en) | 2012-06-14 |
| CA2591786C (en) | 2013-07-16 |
| BRPI0519349A2 (pt) | 2009-01-20 |
| EP2272565A3 (en) | 2012-03-28 |
| US20130164301A1 (en) | 2013-06-27 |
| CN101102819A (zh) | 2008-01-09 |
| CA2591786A1 (en) | 2006-06-29 |
| JP2008525342A (ja) | 2008-07-17 |
| AU2005318464B2 (en) | 2012-02-23 |
| EP1830924B1 (en) | 2013-02-27 |
| MX2007006997A (es) | 2007-10-10 |
| US8119137B2 (en) | 2012-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2514878C2 (ru) | Предотвращение образования и/или стабилизации тромбов | |
| Renné et al. | Defective thrombus formation in mice lacking coagulation factor XII | |
| US11124787B2 (en) | ADAMTS13-containing compositions having thrombolytic activity | |
| Westaby | Aprotinin in perspective | |
| US9243044B2 (en) | Anticoagulant polypeptide and applications thereof | |
| US20030198636A1 (en) | Process for inhibiting complement activation via the alternative pathway | |
| US9574013B2 (en) | Antibodies against factor XII and uses thereof | |
| KR20020062698A (ko) | 혈전성 질환에 대한 보호용 약제 | |
| Renné et al. | Factor XI deficiency in animal models | |
| JP2017501968A (ja) | 第ｘｉｉ因子インヒビターおよびｃ１−インヒビターを使用する組合せ療法 | |
| JP2758162B2 (ja) | 出血疾患の治療方法および治療用組成物 | |
| WO2014043334A1 (en) | Modulation of podoplanin mediated platelet activation | |
| US20080219998A1 (en) | Anti-Thrombotic Agents | |
| HK1116438A (en) | Prevention of thrombus formation and/or stabilization | |
| EP1915175A2 (en) | Direct and indirect effector cell protease receptor-1 (epr-1) inhibitors as antiplatelet agents | |
| Maat | Natural pathways for factor XII activation: Implications for hereditary angioedema | |
| Požgajová | Studies on formation and stabilization of pathological thrombi in vivo | |
| GB2374870A (en) | Use of genetically modified multicellular animals in the identification of drug target proteins | |
| IE872967L (en) | Treatment of bleeding disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20101019 |
|
| FZ9A | Application not withdrawn (correction of the notice of withdrawal) |
Effective date: 20110812 |
|
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20121101 |
|
| FZ9A | Application not withdrawn (correction of the notice of withdrawal) |
Effective date: 20131024 |