FR2504921A1 - Medicament nouveau constitue par un complexe aprotinine-plasmine et procede de preparation de ce nouveau complexe - Google Patents
Medicament nouveau constitue par un complexe aprotinine-plasmine et procede de preparation de ce nouveau complexe Download PDFInfo
- Publication number
- FR2504921A1 FR2504921A1 FR8108681A FR8108681A FR2504921A1 FR 2504921 A1 FR2504921 A1 FR 2504921A1 FR 8108681 A FR8108681 A FR 8108681A FR 8108681 A FR8108681 A FR 8108681A FR 2504921 A1 FR2504921 A1 FR 2504921A1
- Authority
- FR
- France
- Prior art keywords
- aprotinin
- plasmin
- complex
- plasminogen
- sep
- 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.)
- Granted
Links
- ZPNFWUPYTFPOJU-MPSLMFKFSA-N aprotinin Chemical compound CC[C@H](C)[C@@H]1NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CSSC[C@H]3NC(=O)CNC(=O)CNC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[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](Cc4ccccc4)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)NC3=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](Cc3ccccc3)NC(=O)[C@@H](CC(O)=O)NC(=O)[C@H]3CCCN3C(=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)N3CCC[C@@H]3C(=O)N3CCC[C@H]3C(=O)N[C@H](Cc3ccc(O)cc3)C(=O)N[C@H]([C@H](C)O)C(=O)NCC(=O)N3CCC[C@H]3C(=O)N2)C(=O)NCC(=O)NCC(=O)N[C@H](C)C(O)=O)NC(=O)[C@@H](CC(C)C)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](NC1=O)[C@H](C)CC)[C@@H](C)O)C(C)C ZPNFWUPYTFPOJU-MPSLMFKFSA-N 0.000 title abstract description 4
- 238000004519 manufacturing process Methods 0.000 title description 3
- 229940126601 medicinal product Drugs 0.000 title 1
- 108010051456 Plasminogen Proteins 0.000 claims abstract description 22
- 102000013566 Plasminogen Human genes 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000012190 activator Substances 0.000 claims abstract description 12
- 239000002243 precursor Substances 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 229940012957 plasmin Drugs 0.000 claims description 78
- 108010039627 Aprotinin Proteins 0.000 claims description 66
- 229960004405 aprotinin Drugs 0.000 claims description 65
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 claims description 62
- 108010088842 Fibrinolysin Proteins 0.000 claims description 45
- 229960005356 urokinase Drugs 0.000 claims description 11
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 10
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 238000011534 incubation Methods 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 239000002547 new drug Substances 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 4
- 229960002684 aminocaproic acid Drugs 0.000 claims description 4
- 238000010668 complexation reaction Methods 0.000 claims description 4
- 108010087750 lysyl-plasminogen Proteins 0.000 claims description 4
- 230000002829 reductive effect Effects 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 2
- 239000013612 plasmid Substances 0.000 claims 1
- 230000003480 fibrinolytic effect Effects 0.000 abstract description 13
- 239000003527 fibrinolytic agent Substances 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 4
- 238000011282 treatment Methods 0.000 abstract description 4
- 102000009123 Fibrin Human genes 0.000 description 36
- 108010073385 Fibrin Proteins 0.000 description 36
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 36
- 229950003499 fibrin Drugs 0.000 description 36
- 239000008280 blood Substances 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 15
- 230000009089 cytolysis Effects 0.000 description 10
- 230000020764 fibrinolysis Effects 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 241000283973 Oryctolagus cuniculus Species 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 108010023197 Streptokinase Proteins 0.000 description 7
- 108090000190 Thrombin Proteins 0.000 description 7
- 238000005345 coagulation Methods 0.000 description 7
- 230000015271 coagulation Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229960004072 thrombin Drugs 0.000 description 7
- 108090000631 Trypsin Proteins 0.000 description 6
- 102000004142 Trypsin Human genes 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 229960005202 streptokinase Drugs 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 239000012588 trypsin Substances 0.000 description 6
- 108010049003 Fibrinogen Proteins 0.000 description 5
- 102000008946 Fibrinogen Human genes 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229940012952 fibrinogen Drugs 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 210000001367 artery Anatomy 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 description 3
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 108010064755 lys-plasmin Proteins 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001567 anti-fibrinolytic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000012622 synthetic inhibitor Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000820 toxicity test Toxicity 0.000 description 2
- 229940108519 trasylol Drugs 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010071289 Factor XIII Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 description 1
- 206010020608 Hypercoagulation Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- 108010076857 N(alpha)-acetylglycyllysyl methyl ester Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 229940122791 Plasmin inhibitor Drugs 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125507 complex inhibitor Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000502 dialysis 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
- 239000006185 dispersion Substances 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940066758 endopeptidases Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000000058 esterolytic effect Effects 0.000 description 1
- YQDHCCVUYCIGSW-LBPRGKRZSA-N ethyl (2s)-2-benzamido-5-(diaminomethylideneamino)pentanoate Chemical compound NC(=N)NCCC[C@@H](C(=O)OCC)NC(=O)C1=CC=CC=C1 YQDHCCVUYCIGSW-LBPRGKRZSA-N 0.000 description 1
- 229940012444 factor xiii Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229940106780 human fibrinogen Drugs 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000003027 hypercoagulation Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 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 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- FIGKGJVUYAFLBI-VIFPVBQESA-N methyl (2s)-2-[(2-acetamidoacetyl)amino]-6-aminohexanoate Chemical compound NCCCC[C@@H](C(=O)OC)NC(=O)CNC(C)=O FIGKGJVUYAFLBI-VIFPVBQESA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 230000018341 negative regulation of fibrinolysis Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002806 plasmin inhibitor Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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 1
- 239000000758 substrate Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6435—Plasmin (3.4.21.7), i.e. fibrinolysin
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21007—Plasmin (3.4.21.7), i.e. fibrinolysin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8108681A FR2504921A1 (fr) | 1981-04-30 | 1981-04-30 | Medicament nouveau constitue par un complexe aprotinine-plasmine et procede de preparation de ce nouveau complexe |
| PCT/FR1982/000078 WO1982003772A1 (en) | 1981-04-30 | 1982-04-29 | New medicine comprised by an aprotinine-plasmine complex and method for the preparation of such new complex |
| JP57501460A JPS58500610A (ja) | 1981-04-30 | 1982-04-29 | アプロチニン−プラスミン錯体からなる新規な医薬，及びその新規な錯体の製造方法 |
| EP19820901356 EP0077796A1 (fr) | 1981-04-30 | 1982-04-29 | Medicament nouveau constitue par un complexe aprotinine-plasmine et procede de preparation de ce nouveau complexe |
| DK578682A DK578682A (da) | 1981-04-30 | 1982-12-29 | Nyt laegemiddel bestaaende af et aprotinin-plasmin-kompleks og fremgangsmaade til fremstilling af det nye kompleks |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8108681A FR2504921A1 (fr) | 1981-04-30 | 1981-04-30 | Medicament nouveau constitue par un complexe aprotinine-plasmine et procede de preparation de ce nouveau complexe |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FR2504921A1 true FR2504921A1 (fr) | 1982-11-05 |
| FR2504921B1 FR2504921B1 (enrdf_load_stackoverflow) | 1985-05-17 |
Family
ID=9257969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8108681A Granted FR2504921A1 (fr) | 1981-04-30 | 1981-04-30 | Medicament nouveau constitue par un complexe aprotinine-plasmine et procede de preparation de ce nouveau complexe |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0077796A1 (enrdf_load_stackoverflow) |
| JP (1) | JPS58500610A (enrdf_load_stackoverflow) |
| FR (1) | FR2504921A1 (enrdf_load_stackoverflow) |
| WO (1) | WO1982003772A1 (enrdf_load_stackoverflow) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0952215A3 (en) * | 1998-04-24 | 2002-06-26 | Aventis Behring Gesellschaft mit beschränkter Haftung | Protease for activating clotting factor VII |
| US7892842B2 (en) | 1998-04-24 | 2011-02-22 | Csl Behring Gmbh | Procedure for the determination of the activity of the protease which activates factor VII from protein solutions |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3119157A1 (de) * | 1981-05-14 | 1982-12-09 | Behringwerke Ag, 3550 Marburg | Verfahren zur herstellung von und danach hergestelltes plasminogen |
| JPH0768274B2 (ja) * | 1987-03-27 | 1995-07-26 | 株式会社ミドリ十字 | プラスミノゲンの製造方法 |
| GB8721951D0 (en) * | 1987-09-18 | 1987-10-28 | Thrombosis Research Trust | Organic compounds |
| JP2764264B2 (ja) * | 1987-10-01 | 1998-06-11 | 株式会社ミドリ十字 | 線溶活性増強剤 |
| US7202066B2 (en) * | 2002-01-29 | 2007-04-10 | Carrington Laboratories, Inc. | Combination of a growth factor and a protease enzyme |
| CN117568445B (zh) * | 2024-01-18 | 2024-04-09 | 西南交通大学 | 一种tat、pic复合质控品的制备方法及其应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2711164A1 (de) * | 1976-03-18 | 1977-09-29 | Leuven Research & Dev V Z W Lo | Antiplasmin und ein antiserum dagegen |
-
1981
- 1981-04-30 FR FR8108681A patent/FR2504921A1/fr active Granted
-
1982
- 1982-04-29 WO PCT/FR1982/000078 patent/WO1982003772A1/en not_active Application Discontinuation
- 1982-04-29 EP EP19820901356 patent/EP0077796A1/fr not_active Ceased
- 1982-04-29 JP JP57501460A patent/JPS58500610A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2711164A1 (de) * | 1976-03-18 | 1977-09-29 | Leuven Research & Dev V Z W Lo | Antiplasmin und ein antiserum dagegen |
Non-Patent Citations (1)
| Title |
|---|
| CA1981 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6528299B1 (en) | 1996-04-24 | 2003-03-04 | Aventis Behring Gmbh | Protease for activating clotting factor VII |
| EP0952215A3 (en) * | 1998-04-24 | 2002-06-26 | Aventis Behring Gesellschaft mit beschränkter Haftung | Protease for activating clotting factor VII |
| US6911334B2 (en) | 1998-04-24 | 2005-06-28 | Zlb Behring Gmbh | Protease for activating clotting factor VII |
| US7879803B2 (en) | 1998-04-24 | 2011-02-01 | Csl Behring Gmbh | Methods of treatment involving the protease for activating clotting factor VII |
| US7892842B2 (en) | 1998-04-24 | 2011-02-22 | Csl Behring Gmbh | Procedure for the determination of the activity of the protease which activates factor VII from protein solutions |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1982003772A1 (en) | 1982-11-11 |
| EP0077796A1 (fr) | 1983-05-04 |
| FR2504921B1 (enrdf_load_stackoverflow) | 1985-05-17 |
| JPS58500610A (ja) | 1983-04-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Esmon et al. | Protein C activation | |
| Vandooren et al. | Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade | |
| KR100291529B1 (ko) | 단백질 씨 유도체 | |
| EP0513316B1 (fr) | Marqueurs analytiques pour le cancer, notamment pour le cancer malin du sein | |
| CA1227132A (fr) | Preparation a activite collagenolytique ayant une activite elevee et compositions pharmaceutiques la contenant | |
| Toombs | Alfimeprase: pharmacology of a novel fibrinolytic metalloproteinase for thrombolysis | |
| FR2593393A1 (fr) | Solution aqueuse a usage parenteral d'activateur tissulaire du plasminogene, procede pour la preparer et recipient obture la contenant | |
| BE1001425A4 (fr) | Utilisation de l'activateur tissulaire du plasminogene, son association avec une superoxyde-dismutase et formulation pharmaceutique contenant cette association. | |
| FR2583984A1 (fr) | Formulation pharmaceutique lyophilisee d'activateur tissulaire du plasminogene, procede pour la preparer, recipient obture la contenant et sel d'activateur tissulaire du plasminogene | |
| JPH0357749B2 (enrdf_load_stackoverflow) | ||
| WO1998029144A1 (fr) | Procede de preparation d'une colle biologique | |
| US4446316A (en) | Dextran derivative of fibrinolysin | |
| FR2597883A1 (fr) | Nouveaux polypeptides activateurs du plasminogene de type tissulaire humain | |
| EP0346241B1 (fr) | Procédé de préparation d'une fraction concentrée en facteur Vlla et son application à titre de médicament | |
| CN1049865A (zh) | 纯尿激酶酶原与人血清白蛋白通过二硫桥键共价连接形成的血纤维蛋白溶酶原激活剂复合物 | |
| FR2504921A1 (fr) | Medicament nouveau constitue par un complexe aprotinine-plasmine et procede de preparation de ce nouveau complexe | |
| CA3029075A1 (fr) | Fibrinogene liquide stable | |
| Zhang et al. | Bio-inspired liposomal thrombomodulin conjugate through bio-orthogonal chemistry | |
| WO2002100337A2 (en) | Antithrombotic thrombin variants | |
| CH626808A5 (enrdf_load_stackoverflow) | ||
| JPH07143878A (ja) | 改善された繊維素溶解性及びトロンビン阻害作用を有する２官能性ウロキナーゼ変異体 | |
| SU1022988A1 (ru) | Стабилизированна урокиназа,обладающа тромболитической активностью,и способ ее получени | |
| FR2948665A1 (fr) | Procede pour la purification de proteines de la coagulation a domaine gla actives | |
| JPH01240186A (ja) | フィブリン特異性２本鎖プラスミノーゲンアクチベーター | |
| JPS59118717A (ja) | プラスミノーゲン活性化剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ST | Notification of lapse |