JP2015508054A5 - - Google Patents

Info

Publication number

JP2015508054A5

JP2015508054A5 JP2014553633A JP2014553633A JP2015508054A5 JP 2015508054 A5 JP2015508054 A5 JP 2015508054A5 JP 2014553633 A JP2014553633 A JP 2014553633A JP 2014553633 A JP2014553633 A JP 2014553633A JP 2015508054 A5 JP2015508054 A5 JP 2015508054A5

Authority

JP

Japan

Prior art keywords

cells

inhibitor

factor

combination

direct

Prior art date

2012-06-15

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 210000004027 cell Anatomy 0.000 claims 14
• 210000000130 stem cell Anatomy 0.000 claims 8
• 229940123688 Direct Factor Xa inhibitor Drugs 0.000 claims 7
• 229940123583 Factor Xa inhibitor Drugs 0.000 claims 7
• 210000004185 liver Anatomy 0.000 claims 6
• 229940122388 Thrombin inhibitor Drugs 0.000 claims 5
• 239000008194 pharmaceutical composition Substances 0.000 claims 5
• 239000003868 thrombin inhibitor Substances 0.000 claims 5
• 229940122093 Indirect Factor Xa inhibitor Drugs 0.000 claims 4
• 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 claims 4
• 239000012190 activator Substances 0.000 claims 4
• 239000004019 antithrombin Substances 0.000 claims 4
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 4
• 238000002054 transplantation Methods 0.000 claims 4
• 108010055460 bivalirudin Proteins 0.000 claims 3
• 229960001500 bivalirudin Drugs 0.000 claims 3
• OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin 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(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 3
• 238000000034 method Methods 0.000 claims 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims 3
• -1 retaxane Chemical compound 0.000 claims 3
• 102000009027 Albumins Human genes 0.000 claims 2
• 108010088751 Albumins Proteins 0.000 claims 2
• 108010007267 Hirudins Proteins 0.000 claims 2
• 102000007625 Hirudins Human genes 0.000 claims 2
• 102000004877 Insulin Human genes 0.000 claims 2
• 108090001061 Insulin Proteins 0.000 claims 2
• 102000018317 Keratin-19 Human genes 0.000 claims 2
• 108010066302 Keratin-19 Proteins 0.000 claims 2
• 108010000499 Thromboplastin Proteins 0.000 claims 2
• 102000002262 Thromboplastin Human genes 0.000 claims 2
• 208000007536 Thrombosis Diseases 0.000 claims 2
• 210000003494 hepatocyte Anatomy 0.000 claims 2
• 229940006607 hirudin Drugs 0.000 claims 2
• WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin 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(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 2
• 238000001727 in vivo Methods 0.000 claims 2
• 230000002401 inhibitory effect Effects 0.000 claims 2
• 229940125396 insulin Drugs 0.000 claims 2
• 210000005229 liver cell Anatomy 0.000 claims 2
• 210000005009 osteogenic cell Anatomy 0.000 claims 2
• 230000002265 prevention Effects 0.000 claims 2
• 230000002947 procoagulating effect Effects 0.000 claims 2
• 229960001148 rivaroxaban Drugs 0.000 claims 2
• KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 claims 2
• 230000001732 thrombotic effect Effects 0.000 claims 2
• NOBZETMXGVAWIM-UHFFFAOYSA-N 4-[(2-carbamimidoyl-3,4-dihydro-1h-isoquinolin-7-yl)oxymethyl]-1-pyridin-4-ylpiperidine-4-carboxylic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=C2CN(C(=N)N)CCC2=CC=C1OCC(CC1)(C(O)=O)CCN1C1=CC=NC=C1 NOBZETMXGVAWIM-UHFFFAOYSA-N 0.000 claims 1
• 102000007469 Actins Human genes 0.000 claims 1
• 108010085238 Actins Proteins 0.000 claims 1
• 101710163968 Antistasin Proteins 0.000 claims 1
• QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 claims 1
• 206010053567 Coagulopathies Diseases 0.000 claims 1
• HGVDHZBSSITLCT-JLJPHGGASA-N Edoxaban Chemical compound N([C@H]1CC[C@@H](C[C@H]1NC(=O)C=1SC=2CN(C)CCC=2N=1)C(=O)N(C)C)C(=O)C(=O)NC1=CC=C(Cl)C=N1 HGVDHZBSSITLCT-JLJPHGGASA-N 0.000 claims 1
• 108090000190 Thrombin Proteins 0.000 claims 1
• 229960003886 apixaban Drugs 0.000 claims 1
• 229960003856 argatroban Drugs 0.000 claims 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 claims 1
• 229950011103 betrixaban Drugs 0.000 claims 1
• XHOLNRLADUSQLD-UHFFFAOYSA-N betrixaban Chemical compound C=1C=C(Cl)C=NC=1NC(=O)C1=CC(OC)=CC=C1NC(=O)C1=CC=C(C(=N)N(C)C)C=C1 XHOLNRLADUSQLD-UHFFFAOYSA-N 0.000 claims 1
• 230000035602 clotting Effects 0.000 claims 1
• 229960003850 dabigatran Drugs 0.000 claims 1
• YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 claims 1
• IJNIQYINMSGIPS-UHFFFAOYSA-N darexaban Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=CC(O)=C1NC(=O)C1=CC=C(N2CCN(C)CCC2)C=C1 IJNIQYINMSGIPS-UHFFFAOYSA-N 0.000 claims 1
• 229950004553 darexaban Drugs 0.000 claims 1
• 229940019332 direct factor xa inhibitors Drugs 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 229960000622 edoxaban Drugs 0.000 claims 1
• 210000002889 endothelial cell Anatomy 0.000 claims 1
• 210000002919 epithelial cell Anatomy 0.000 claims 1
• 238000000338 in vitro Methods 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 claims 1
• 230000005764 inhibitory process Effects 0.000 claims 1
• DKWNMCUOEDMMIN-PKOBYXMFSA-N melagatran Chemical compound C1=CC(C(=N)N)=CC=C1CNC(=O)[C@H]1N(C(=O)[C@H](NCC(O)=O)C2CCCCC2)CC1 DKWNMCUOEDMMIN-PKOBYXMFSA-N 0.000 claims 1
• 229960002137 melagatran Drugs 0.000 claims 1
• 210000000651 myofibroblast Anatomy 0.000 claims 1
• 210000002460 smooth muscle Anatomy 0.000 claims 1
• 229960004072 thrombin Drugs 0.000 claims 1
• ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 claims 1
• 229960001522 ximelagatran Drugs 0.000 claims 1