JP2000507204A - C1―インヒビターの補体及び血液凝固阻害特性の強化 - Google Patents
C1―インヒビターの補体及び血液凝固阻害特性の強化Info
- Publication number
- JP2000507204A JP2000507204A JP9522672A JP52267297A JP2000507204A JP 2000507204 A JP2000507204 A JP 2000507204A JP 9522672 A JP9522672 A JP 9522672A JP 52267297 A JP52267297 A JP 52267297A JP 2000507204 A JP2000507204 A JP 2000507204A
- Authority
- JP
- Japan
- Prior art keywords
- inhibition
- inhibitors
- inhibitor
- esterase
- pharmaceutical composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000000295 complement effect Effects 0.000 title claims abstract description 38
- 230000023555 blood coagulation Effects 0.000 title claims abstract description 26
- 239000003112 inhibitor Substances 0.000 title claims description 94
- 230000002401 inhibitory effect Effects 0.000 title description 13
- 230000005764 inhibitory process Effects 0.000 claims abstract description 67
- 229940009550 c1 esterase inhibitor Drugs 0.000 claims abstract description 66
- 229960000633 dextran sulfate Drugs 0.000 claims abstract description 39
- 239000002329 esterase inhibitor Substances 0.000 claims abstract description 17
- 108010028774 Complement C1 Proteins 0.000 claims abstract description 14
- 239000003527 fibrinolytic agent Substances 0.000 claims abstract description 13
- 230000003480 fibrinolytic effect Effects 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 206010040047 Sepsis Diseases 0.000 claims abstract description 5
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 5
- 102000016917 Complement C1 Human genes 0.000 claims abstract 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 241000894007 species Species 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 13
- 230000001225 therapeutic effect Effects 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 230000000069 prophylactic effect Effects 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
- 229920002307 Dextran Polymers 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000012620 biological material Substances 0.000 claims description 2
- 229960002086 dextran Drugs 0.000 claims description 2
- 239000006069 physical mixture Substances 0.000 claims description 2
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract 1
- 108010080805 Factor XIa Proteins 0.000 description 43
- 102000055157 Complement C1 Inhibitor Human genes 0.000 description 41
- 108700040183 Complement C1 Inhibitor Proteins 0.000 description 41
- 229920002683 Glycosaminoglycan Polymers 0.000 description 39
- 230000000694 effects Effects 0.000 description 39
- 230000004913 activation Effects 0.000 description 31
- 229920000669 heparin Polymers 0.000 description 31
- 229960002897 heparin Drugs 0.000 description 31
- 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 28
- 101100329495 Mus musculus C1sa gene Proteins 0.000 description 21
- 101100329496 Mus musculus C1sb gene Proteins 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 20
- 102000035195 Peptidases Human genes 0.000 description 15
- 108091005804 Peptidases Proteins 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 108010074864 Factor XI Proteins 0.000 description 14
- 230000024203 complement activation Effects 0.000 description 14
- 239000003001 serine protease inhibitor Substances 0.000 description 13
- 108010080865 Factor XII Proteins 0.000 description 12
- 102000000429 Factor XII Human genes 0.000 description 12
- 206010061218 Inflammation Diseases 0.000 description 12
- 108060005987 Kallikrein Proteins 0.000 description 12
- 102000001399 Kallikrein Human genes 0.000 description 12
- 230000004054 inflammatory process Effects 0.000 description 12
- 230000037361 pathway Effects 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 102000004411 Antithrombin III Human genes 0.000 description 11
- 108090000935 Antithrombin III Proteins 0.000 description 11
- 108010071241 Factor XIIa Proteins 0.000 description 11
- 229960005348 antithrombin iii Drugs 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 229920002971 Heparan sulfate Polymers 0.000 description 10
- 102000008847 Serpin Human genes 0.000 description 10
- 108050000761 Serpin Proteins 0.000 description 10
- 230000003024 amidolytic effect Effects 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 229920000045 Dermatan sulfate Polymers 0.000 description 9
- 239000004365 Protease Substances 0.000 description 9
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 9
- 230000002779 inactivation Effects 0.000 description 9
- 241000557626 Corvus corax Species 0.000 description 8
- 229940051593 dermatan sulfate Drugs 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 102100035991 Alpha-2-antiplasmin Human genes 0.000 description 7
- 102100025406 Complement C1s subcomponent Human genes 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 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 6
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 150000004676 glycans Chemical class 0.000 description 6
- 229920001282 polysaccharide Polymers 0.000 description 6
- 239000005017 polysaccharide Substances 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 235000019833 protease Nutrition 0.000 description 6
- 239000012190 activator Substances 0.000 description 5
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 5
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 5
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000004154 complement system Effects 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 235000019419 proteases Nutrition 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 208000034158 bleeding Diseases 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000015271 coagulation Effects 0.000 description 4
- 238000005345 coagulation Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000020764 fibrinolysis Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 108010089414 Anaphylatoxins Proteins 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 108090000955 Complement C2 Proteins 0.000 description 3
- 102000004381 Complement C2 Human genes 0.000 description 3
- 108010067641 Complement C3-C5 Convertases Proteins 0.000 description 3
- 102000016574 Complement C3-C5 Convertases Human genes 0.000 description 3
- 108010034753 Complement Membrane Attack Complex Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 108090000190 Thrombin Proteins 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 3
- 235000011130 ammonium sulphate Nutrition 0.000 description 3
- 230000002429 anti-coagulating effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229960004072 thrombin Drugs 0.000 description 3
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- 206010048998 Acute phase reaction Diseases 0.000 description 2
- 229940124073 Complement inhibitor Drugs 0.000 description 2
- 102100031673 Corneodesmosin Human genes 0.000 description 2
- 101710139375 Corneodesmosin Proteins 0.000 description 2
- 102100033299 Glia-derived nexin Human genes 0.000 description 2
- 101710183811 Glia-derived nexin Proteins 0.000 description 2
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 101000783712 Homo sapiens Alpha-2-antiplasmin Proteins 0.000 description 2
- 241000242362 Kordia Species 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 102100027637 Plasma protease C1 inhibitor Human genes 0.000 description 2
- 108050007539 Plasma protease C1 inhibitor Proteins 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- NAXKFVIRJICPAO-LHNWDKRHSA-N [(1R,3S,4R,6R,7R,9S,10S,12R,13S,15S,16R,18S,19S,21S,22S,24S,25S,27S,28R,30R,31R,33S,34S,36R,37R,39R,40S,42R,44R,46S,48S,50R,52S,54S,56S)-46,48,50,52,54,56-hexakis(hydroxymethyl)-2,8,14,20,26,32,38,43,45,47,49,51,53,55-tetradecaoxa-5,11,17,23,29,35,41-heptathiapentadecacyclo[37.3.2.23,7.29,13.215,19.221,25.227,31.233,37.04,6.010,12.016,18.022,24.028,30.034,36.040,42]hexapentacontan-44-yl]methanol Chemical compound OC[C@H]1O[C@H]2O[C@H]3[C@H](CO)O[C@H](O[C@H]4[C@H](CO)O[C@H](O[C@@H]5[C@@H](CO)O[C@H](O[C@H]6[C@H](CO)O[C@H](O[C@H]7[C@H](CO)O[C@@H](O[C@H]8[C@H](CO)O[C@@H](O[C@@H]1[C@@H]1S[C@@H]21)[C@@H]1S[C@H]81)[C@H]1S[C@@H]71)[C@H]1S[C@H]61)[C@H]1S[C@@H]51)[C@H]1S[C@@H]41)[C@H]1S[C@H]31 NAXKFVIRJICPAO-LHNWDKRHSA-N 0.000 description 2
- 230000004658 acute-phase response Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 239000004074 complement inhibitor Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 150000002066 eicosanoids Chemical class 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000006624 extrinsic pathway Effects 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229940036107 hepatitis b immunoglobulin Drugs 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 239000000976 ink Substances 0.000 description 2
- 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 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229940012957 plasmin Drugs 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- -1 polypropylene Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000197 pyrolysis Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- 229940038773 trisodium citrate Drugs 0.000 description 2
- 239000002753 trypsin inhibitor Substances 0.000 description 2
- 230000008728 vascular permeability Effects 0.000 description 2
- FPJHWYCPAOPVIV-VOZMEZHOSA-N (2R,3S,4R,5R,6R)-6-[(2R,3R,4R,5R,6R)-5-acetamido-2-(hydroxymethyl)-6-methoxy-3-sulfooxyoxan-4-yl]oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical compound CO[C@@H]1O[C@H](CO)[C@H](OS(O)(=O)=O)[C@H](O[C@@H]2O[C@H]([C@@H](OC)[C@H](O)[C@H]2O)C(O)=O)[C@H]1NC(C)=O FPJHWYCPAOPVIV-VOZMEZHOSA-N 0.000 description 1
- WPVINHLVHHPBMK-ULQDDVLXSA-N (2s)-n-[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]-1-[(2s)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide Chemical compound C([C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC=2C=CC(=CC=2)[N+]([O-])=O)CCN1C(=O)[C@@H]1CCC(=O)N1 WPVINHLVHHPBMK-ULQDDVLXSA-N 0.000 description 1
- KZKAYEGOIJEWQB-UHFFFAOYSA-N 1,3-dibromopropane;n,n,n',n'-tetramethylhexane-1,6-diamine Chemical compound BrCCCBr.CN(C)CCCCCCN(C)C KZKAYEGOIJEWQB-UHFFFAOYSA-N 0.000 description 1
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-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
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 101710081722 Antitrypsin Proteins 0.000 description 1
- 241000507564 Aplanes Species 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 241000283690 Bos taurus Species 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
- 108010034358 Classical Pathway Complement C3 Convertase Proteins 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 108010028780 Complement C3 Proteins 0.000 description 1
- 102000016918 Complement C3 Human genes 0.000 description 1
- 108010078015 Complement C3b Proteins 0.000 description 1
- 108010028778 Complement C4 Proteins 0.000 description 1
- 108010078546 Complement C5a Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 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
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 101710097382 Fibrinolytic protease Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010062713 Haemorrhagic diathesis Diseases 0.000 description 1
- 108090000481 Heparin Cofactor II Proteins 0.000 description 1
- 108010022901 Heparin Lyase Proteins 0.000 description 1
- 102100030500 Heparin cofactor 2 Human genes 0.000 description 1
- 206010019860 Hereditary angioedema Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 1
- 101000595925 Homo sapiens Plasminogen-like protein B Proteins 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010077861 Kininogens Proteins 0.000 description 1
- 102000010631 Kininogens Human genes 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 208000004221 Multiple Trauma Diseases 0.000 description 1
- 101100004031 Mus musculus Aven gene Proteins 0.000 description 1
- 101100355584 Mus musculus Rad51 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 108090000113 Plasma Kallikrein Proteins 0.000 description 1
- 102100038124 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 102100035195 Plasminogen-like protein B Human genes 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 101100545004 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YSP2 gene Proteins 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000004732 Systemic Vasculitis Diseases 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 description 1
- 101710139626 Tissue factor pathway inhibitor Proteins 0.000 description 1
- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 1
- 108010059382 Zea mays trypsin inhibitor Proteins 0.000 description 1
- 229920000392 Zymosan Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002001 anti-metastasis Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 230000001475 anti-trypsic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002257 antimetastatic agent Substances 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 208000037516 chromosome inversion disease Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 239000002642 cobra venom Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 229950007870 hexadimethrine bromide Drugs 0.000 description 1
- 239000013628 high molecular weight specie Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 238000003367 kinetic assay Methods 0.000 description 1
- GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 1
- OTZRAYGBFWZKMX-JUDRUQEKSA-N leukotriene E4 Chemical compound CCCCCC=CCC=C\C=C\C=C\[C@@H](SC[C@H](N)C(O)=O)[C@@H](O)CCCC(O)=O OTZRAYGBFWZKMX-JUDRUQEKSA-N 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000013627 low molecular weight specie Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000017570 negative regulation of blood coagulation Effects 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 230000031978 negative regulation of complement activation Effects 0.000 description 1
- 230000011242 neutrophil chemotaxis Effects 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229940110272 plasma derived c1-inhibitor Drugs 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 108010054213 protease C1 Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008718 systemic inflammatory response Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 150000005671 trienes Chemical class 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- UOCLRXFKRLRMKV-UHFFFAOYSA-N trolnitrate phosphate Chemical compound OP(O)(O)=O.OP(O)(O)=O.[O-][N+](=O)OCCN(CCO[N+]([O-])=O)CCO[N+]([O-])=O UOCLRXFKRLRMKV-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- 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
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Rheumatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Compounds Of Unknown Constitution (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP95203537 | 1995-12-18 | ||
| EP95203537.6 | 1995-12-18 | ||
| PCT/NL1996/000488 WO1997022347A1 (en) | 1995-12-18 | 1996-12-18 | Potentiation of complement and coagulation inhibitory properties of c1-inhibitor. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000507204A true JP2000507204A (ja) | 2000-06-13 |
Family
ID=8220969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9522672A Pending JP2000507204A (ja) | 1995-12-18 | 1996-12-18 | C1―インヒビターの補体及び血液凝固阻害特性の強化 |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0868191A1 (de) |
| JP (1) | JP2000507204A (de) |
| AU (1) | AU1042597A (de) |
| WO (1) | WO1997022347A1 (de) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023521919A (ja) * | 2020-04-15 | 2023-05-25 | ティーエックス メディック エービー | 敗血症および高サイトカイン血症の治療薬 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2502539A1 (en) * | 2002-10-17 | 2004-04-29 | Pharming Intellectual Property B.V. | Protein modification |
| SMT201900141T1 (it) | 2013-03-15 | 2019-05-10 | Shire Viropharma Inc | Composizioni di c1-inh e metodi per la prevenzione e il trattamento di disturbi associati a deficit di inibitore di c1 esterasi |
| US20150104445A1 (en) * | 2013-10-10 | 2015-04-16 | Viropharma Holdings Limited | Methods of inhibiting the alternative pathway of complement immune system activation and compositions used therein |
| SE539575C2 (en) | 2015-07-30 | 2017-10-17 | Tx Medic Ab | Dextran sulfate for use in treating, inhibiting or preventing cardiac fibrosis |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3634392A1 (de) * | 1986-10-09 | 1988-04-14 | Knoll Ag | Verwendung polysulfatierter niedermolekularer dextransulfate |
| IL85145A (en) * | 1987-01-23 | 1994-08-26 | Univ Australian | Anti-metastatic pharmacological or veterinary preparations containing modified herpin with reduced anticoagulant activity |
| EP0293826A3 (de) * | 1987-06-02 | 1989-05-10 | Stichting REGA V.Z.W. | Therapeutische und prophylaktische Gabe von sulfatierten Polysacchariden gegen AIDS |
| AU6879091A (en) * | 1989-10-16 | 1991-05-16 | Invitron Corporation | Protease nexin i/dextran sulfate anticoagulant |
| ATE135585T1 (de) * | 1990-08-27 | 1996-04-15 | Monsanto Co | Anticoagulatorische zusammensetzung aus laci und sulfatierten polysacchariden |
| WO1992022320A1 (en) * | 1991-06-14 | 1992-12-23 | Genentech, Inc. | C1 inhibitor variants and treating inflammatory response with c1 inhibitor |
| DE4244735A1 (de) * | 1992-08-24 | 1994-03-31 | Behringwerke Ag | Verwendung von C1-Inaktivator zur Bekämpfung von Komplikationen bei der Anwendung von Zytokinen, endogenen Mediatoren, gentechnisch produzierten Mediator-Hybriden oder Wachstumsfaktoren im Rahmen der therapeutischen Anwendung dieser Substanzen |
-
1996
- 1996-12-18 EP EP96941227A patent/EP0868191A1/de not_active Withdrawn
- 1996-12-18 AU AU10425/97A patent/AU1042597A/en not_active Abandoned
- 1996-12-18 WO PCT/NL1996/000488 patent/WO1997022347A1/en not_active Ceased
- 1996-12-18 JP JP9522672A patent/JP2000507204A/ja active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023521919A (ja) * | 2020-04-15 | 2023-05-25 | ティーエックス メディック エービー | 敗血症および高サイトカイン血症の治療薬 |
| JP7758356B2 (ja) | 2020-04-15 | 2025-10-22 | ティーエックス メディック エービー | 敗血症および高サイトカイン血症の治療薬 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997022347A1 (en) | 1997-06-26 |
| AU1042597A (en) | 1997-07-14 |
| EP0868191A1 (de) | 1998-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wuillemin et al. | Potentiation of C1 inhibitor by glycosaminoglycans: dextran sulfate species are effective inhibitors of in vitro complement activation in plasma | |
| Olson et al. | Regulation of thrombin activity by antithrombin and heparin | |
| EP0497756B1 (de) | Antithrombotische zusammensetzung | |
| Day et al. | Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit | |
| Luchtman-Jones et al. | The current status of coagulation | |
| JPS6218401A (ja) | 結合組織病理において有効な医薬の製造に使用する多糖およびオリゴ糖 | |
| Castelino et al. | Natural anticoagulants and the liver | |
| US5777081A (en) | Process for producing an inter-alpha-trypsin inhibitor concentrate for therapeutic use and concentrate thus obtained | |
| EP0473564B1 (de) | Anticoagulatorische Zusammensetzung aus LACI und sulfatierten Polysacchariden | |
| Abbink et al. | Quantification of functional and inactivated α2-macroglobulin in sepsis | |
| Vinazzer | Hereditary and acquired antithrombin deficiency | |
| Abildgaard | Antithrombin–early prophecies and present challenges | |
| JP2000507204A (ja) | C1―インヒビターの補体及び血液凝固阻害特性の強化 | |
| US7008933B2 (en) | Process for prophylaxis and therapy of thrombotic processes employing heparin having particular average molecular weights | |
| JPH08511764A (ja) | 好中球エラスターゼ及びカテプシンgの阻害方法及び阻害薬 | |
| Wuillemin et al. | Clearance of human factor XIa–inhibitor complexes in rats | |
| Bridey et al. | Recombinant hirudin (HBW 023): Biological data of ten patients with severe venous thrombo‐embolism | |
| CA2239787A1 (en) | Potentiation of complement and coagulation inhibitory properties of c1-inhibitor | |
| Kaiser et al. | Recombinant TFPI and variants: potential implications in the treatment of cardiovascular disorders | |
| Mattsson et al. | Antithrombotic properties in rabbits of heparin and heparin fragments covalently coupled to human antithrombin III. | |
| US20050014701A1 (en) | Combination product comprising melagatran and dexamethasone | |
| US6291427B1 (en) | Anticoagulant combination of LACI and sulfated polysaccharides | |
| US20010055591A1 (en) | Antithrombin H-helix mutants | |
| AU2002363023A1 (en) | A combination product comprising melagatran and dexamethasone | |
| Jeske | Pharmacologic studies on synthetic analogues of heparin with selective affinity to endogenous serine protease inhibitors |