CA1319610C - Methode d'induction de la production endogene de l'activateur tissulaire du plasminogene - Google Patents

Methode d'induction de la production endogene de l'activateur tissulaire du plasminogene

Info

Publication number: CA1319610C
Authority: CA; Canada
Prior art keywords: tpa; paf; cells; basic; levels
Prior art date: 1986-10-31
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.): Expired - Fee Related

Application number

CA000550845A

Other languages

English (en)

Inventor

David A. Moscatelli

David F. Carmichael

Daniel B. Rifkin

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Individual

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

1986-10-31

Filing date

1987-10-29

Publication date

1993-06-29

1987-10-29 Application filed by Individual filed Critical Individual

1993-06-29 Application granted granted Critical

1993-06-29 Publication of CA1319610C publication Critical patent/CA1319610C/fr

2010-06-29 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

102000003978 Tissue Plasminogen Activator Human genes 0.000 title abstract description 68
108090000373 Tissue Plasminogen Activator Proteins 0.000 title abstract description 68
229960000187 tissue plasminogen activator Drugs 0.000 title abstract description 68
238000000034 method Methods 0.000 title abstract description 36
238000004519 manufacturing process Methods 0.000 title description 11
230000001939 inductive effect Effects 0.000 title description 3
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 26
229960002897 heparin Drugs 0.000 claims abstract description 26
229920000669 heparin Polymers 0.000 claims abstract description 26
239000008194 pharmaceutical composition Substances 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 2
230000000694 effects Effects 0.000 abstract description 23
239000002870 angiogenesis inducing agent Substances 0.000 abstract description 12
229940012957 plasmin Drugs 0.000 abstract description 8
208000010125 myocardial infarction Diseases 0.000 abstract description 7
208000007536 Thrombosis Diseases 0.000 abstract description 6
230000006698 induction Effects 0.000 abstract description 6
239000000825 pharmaceutical preparation Substances 0.000 abstract description 6
210000002826 placenta Anatomy 0.000 abstract description 6
239000004480 active ingredient Substances 0.000 abstract description 5
230000015572 biosynthetic process Effects 0.000 abstract description 4
230000004087 circulation Effects 0.000 abstract description 4
238000004090 dissolution Methods 0.000 abstract description 4
238000003786 synthesis reaction Methods 0.000 abstract description 4
206010053567 Coagulopathies Diseases 0.000 abstract description 3
230000002792 vascular Effects 0.000 abstract description 3
230000028327 secretion Effects 0.000 abstract description 2
108010088842 Fibrinolysin Proteins 0.000 abstract 2
108090000790 Enzymes Proteins 0.000 abstract 1
102000004190 Enzymes Human genes 0.000 abstract 1
229940088598 enzyme Drugs 0.000 abstract 1
210000004027 cell Anatomy 0.000 description 100
102000001938 Plasminogen Activators Human genes 0.000 description 48
108010001014 Plasminogen Activators Proteins 0.000 description 48
229940127126 plasminogen activator Drugs 0.000 description 48
206010073071 hepatocellular carcinoma Diseases 0.000 description 27
210000002966 serum Anatomy 0.000 description 26
239000003636 conditioned culture medium Substances 0.000 description 20
239000002609 medium Substances 0.000 description 18
239000000284 extract Substances 0.000 description 17
238000003556 assay Methods 0.000 description 15
210000002889 endothelial cell Anatomy 0.000 description 15
241000283690 Bos taurus Species 0.000 description 13
235000018102 proteins Nutrition 0.000 description 13
102000004169 proteins and genes Human genes 0.000 description 13
108090000623 proteins and genes Proteins 0.000 description 13
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 12
239000002953 phosphate buffered saline Substances 0.000 description 12
239000000499 gel Substances 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
238000001114 immunoprecipitation Methods 0.000 description 10
230000000638 stimulation Effects 0.000 description 10
102000013566 Plasminogen Human genes 0.000 description 9
108010051456 Plasminogen Proteins 0.000 description 9
241000283973 Oryctolagus cuniculus Species 0.000 description 8
230000003511 endothelial effect Effects 0.000 description 8
238000012423 maintenance Methods 0.000 description 8
230000002297 mitogenic effect Effects 0.000 description 8
210000001519 tissue Anatomy 0.000 description 8
108010010803 Gelatin Proteins 0.000 description 7
238000005119 centrifugation Methods 0.000 description 7
239000008273 gelatin Substances 0.000 description 7
229920000159 gelatin Polymers 0.000 description 7
235000019322 gelatine Nutrition 0.000 description 7
235000011852 gelatine desserts Nutrition 0.000 description 7
238000011534 incubation Methods 0.000 description 7
239000000203 mixture Substances 0.000 description 7
230000004044 response Effects 0.000 description 7
108091003079 Bovine Serum Albumin Proteins 0.000 description 6
102000035195 Peptidases Human genes 0.000 description 6
108091005804 Peptidases Proteins 0.000 description 6
239000004365 Protease Substances 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
230000001965 increasing effect Effects 0.000 description 6
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 5
229950003499 fibrin Drugs 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000000243 solution Substances 0.000 description 5
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
229920002684 Sepharose Polymers 0.000 description 4
108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 4
102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 4
210000002403 aortic endothelial cell Anatomy 0.000 description 4
229940098773 bovine serum albumin Drugs 0.000 description 4
239000000872 buffer Substances 0.000 description 4
210000001043 capillary endothelial cell Anatomy 0.000 description 4
238000004113 cell culture Methods 0.000 description 4
210000004351 coronary vessel Anatomy 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000002634 heparin fragment Substances 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
229960005356 urokinase Drugs 0.000 description 4
102000009123 Fibrin Human genes 0.000 description 3
108010073385 Fibrin Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
229930182555 Penicillin Natural products 0.000 description 3
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
239000012083 RIPA buffer Substances 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
239000012190 activator Substances 0.000 description 3
239000011324 bead Substances 0.000 description 3
230000008859 change Effects 0.000 description 3
239000003814 drug Substances 0.000 description 3
210000003953 foreskin Anatomy 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
239000012133 immunoprecipitate Substances 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
238000002955 isolation Methods 0.000 description 3
210000004088 microvessel Anatomy 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
229940049954 penicillin Drugs 0.000 description 3
230000003169 placental effect Effects 0.000 description 3
229920002401 polyacrylamide Polymers 0.000 description 3
229920001296 polysiloxane Polymers 0.000 description 3
230000008569 process Effects 0.000 description 3
229940124272 protein stabilizer Drugs 0.000 description 3
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
238000003860 storage Methods 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
101001051969 Bos taurus Fibroblast growth factor 2 Proteins 0.000 description 2
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 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
108010049003 Fibrinogen Proteins 0.000 description 2
102000008946 Fibrinogen Human genes 0.000 description 2
241000282412 Homo Species 0.000 description 2
101000585555 Homo sapiens PCNA-associated factor Proteins 0.000 description 2
206010061216 Infarction Diseases 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
108020004511 Recombinant DNA Proteins 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
229920004890 Triton X-100 Polymers 0.000 description 2
239000013504 Triton X-100 Substances 0.000 description 2
108090000631 Trypsin Proteins 0.000 description 2
102000004142 Trypsin Human genes 0.000 description 2
239000008272 agar Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
238000010256 biochemical assay Methods 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
230000023555 blood coagulation Effects 0.000 description 2
230000012292 cell migration Effects 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
235000018417 cysteine Nutrition 0.000 description 2
230000009089 cytolysis Effects 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
230000002500 effect on skin Effects 0.000 description 2
238000001962 electrophoresis Methods 0.000 description 2
239000012894 fetal calf serum Substances 0.000 description 2
229940012952 fibrinogen Drugs 0.000 description 2
210000002950 fibroblast Anatomy 0.000 description 2
239000012737 fresh medium Substances 0.000 description 2
239000011521 glass Substances 0.000 description 2
102000048412 human PCLAF Human genes 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
230000007574 infarction Effects 0.000 description 2
YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 2
210000005265 lung cell Anatomy 0.000 description 2
238000002156 mixing Methods 0.000 description 2
239000008188 pellet Substances 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
108090000765 processed proteins & peptides Proteins 0.000 description 2
239000000047 product Substances 0.000 description 2
230000002035 prolonged effect Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
239000000523 sample Substances 0.000 description 2
241000894007 species Species 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
239000000758 substrate Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
230000002459 sustained effect Effects 0.000 description 2
238000010257 thawing Methods 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
239000012588 trypsin Substances 0.000 description 2
210000003606 umbilical vein Anatomy 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
VRJRQOJAEHJQHM-DIKMWTQISA-N (2S)-6-amino-2-[[(2S)-2-[[(2R)-2-aminohexanoyl]amino]-3-(4-hydroxycyclohexyl)propanoyl]amino]-N-(4-nitrophenyl)hexanamide Chemical compound [N+](=O)([O-])C1=CC=C(NC([C@@H](NC([C@@H](NC([C@H](N)CCCC)=O)CC2CCC(CC2)O)=O)CCCCN)=O)C=C1 VRJRQOJAEHJQHM-DIKMWTQISA-N 0.000 description 1
IXNRIBJPEOUGGB-DIKMWTQISA-N (2s)-6-amino-n-[(2r)-2-aminohexanoyl]-n-[(2s)-2-amino-3-(4-hydroxycyclohexyl)propanoyl]-2-(4-nitroanilino)hexanamide Chemical compound C([C@H](N)C(=O)N(C(=O)[C@H](N)CCCC)C(=O)[C@H](CCCCN)NC=1C=CC(=CC=1)[N+]([O-])=O)C1CCC(O)CC1 IXNRIBJPEOUGGB-DIKMWTQISA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
101800004538 Bradykinin Proteins 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
241000237074 Centris Species 0.000 description 1
102000029816 Collagenase Human genes 0.000 description 1
108060005980 Collagenase Proteins 0.000 description 1
238000011537 Coomassie blue staining Methods 0.000 description 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
239000006145 Eagle's minimal essential medium Substances 0.000 description 1
102000001390 Fructose-Bisphosphate Aldolase Human genes 0.000 description 1
108010068561 Fructose-Bisphosphate Aldolase Proteins 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
108010027339 H-norleucyl-hexahydrotyrosyl-lysine-4-nitroanilide Proteins 0.000 description 1
101000605403 Homo sapiens Plasminogen Proteins 0.000 description 1
101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 1
101000638886 Homo sapiens Urokinase-type plasminogen activator Proteins 0.000 description 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
102100035792 Kininogen-1 Human genes 0.000 description 1
102000004407 Lactalbumin Human genes 0.000 description 1
108090000942 Lactalbumin Proteins 0.000 description 1
229920002274 Nalgene Polymers 0.000 description 1
108010065084 Phosphorylase a Proteins 0.000 description 1
206010038563 Reocclusion Diseases 0.000 description 1
241000220317 Rosa Species 0.000 description 1
208000006268 Sarcoma 180 Diseases 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
101710162629 Trypsin inhibitor Proteins 0.000 description 1
229940122618 Trypsin inhibitor Drugs 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
239000011149 active material Substances 0.000 description 1
230000002730 additional effect Effects 0.000 description 1
210000004404 adrenal cortex Anatomy 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
230000027455 binding Effects 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000008512 biological response Effects 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
230000036770 blood supply Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
239000007975 buffered saline Substances 0.000 description 1
244000309466 calf Species 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000032823 cell division Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
210000003855 cell nucleus Anatomy 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
238000010367 cloning Methods 0.000 description 1
229960002424 collagenase Drugs 0.000 description 1
230000001143 conditioned effect Effects 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
229960003964 deoxycholic acid Drugs 0.000 description 1
KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
239000003599 detergent Substances 0.000 description 1
230000029087 digestion Effects 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
238000003182 dose-response assay Methods 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
210000003038 endothelium Anatomy 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
229940125532 enzyme inhibitor Drugs 0.000 description 1
210000002615 epidermis Anatomy 0.000 description 1
239000000208 fibrin degradation product Substances 0.000 description 1
230000003480 fibrinolytic effect Effects 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
208000006454 hepatitis Diseases 0.000 description 1
231100000283 hepatitis Toxicity 0.000 description 1
102000056831 human PLAU Human genes 0.000 description 1
238000005470 impregnation Methods 0.000 description 1
230000000415 inactivating effect Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
210000004347 intestinal mucosa Anatomy 0.000 description 1
229960003299 ketamine Drugs 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000010410 layer Substances 0.000 description 1
238000000464 low-speed centrifugation Methods 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
230000001617 migratory effect Effects 0.000 description 1
239000003595 mist Substances 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
238000002135 phase contrast microscopy Methods 0.000 description 1
PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
230000033885 plasminogen activation Effects 0.000 description 1
229940045627 porcine heparin Drugs 0.000 description 1
229940124606 potential therapeutic agent Drugs 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
238000002731 protein assay Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
239000012723 sample buffer Substances 0.000 description 1
238000009738 saturating Methods 0.000 description 1
238000007790 scraping Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000012679 serum free medium Substances 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
239000002356 single layer Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
239000013589 supplement Substances 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
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 1
229940038773 trisodium citrate Drugs 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
238000005303 weighing Methods 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 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)
- C12N9/6456—Plasminogen activators
- C12N9/6459—Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1825—Fibroblast growth factor [FGF]
- 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)
- C12Y304/21069—Protein C activated (3.4.21.69)

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Zoology (AREA)
Organic Chemistry (AREA)
Wood Science & Technology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Biomedical Technology (AREA)
General Engineering & Computer Science (AREA)
Biochemistry (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Biotechnology (AREA)
Microbiology (AREA)
Gastroenterology & Hepatology (AREA)
Immunology (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Epidemiology (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Enzymes And Modification Thereof (AREA)

CA000550845A 1986-10-31 1987-10-29 Methode d'induction de la production endogene de l'activateur tissulaire du plasminogene Expired - Fee Related CA1319610C (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US92525986A	1986-10-31	1986-10-31
US925,259		1986-10-31

Publications (1)

Publication Number	Publication Date
CA1319610C true CA1319610C (fr)	1993-06-29

Family

ID=25451470

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000550845A Expired - Fee Related CA1319610C (fr)	1986-10-31	1987-10-29	Methode d'induction de la production endogene de l'activateur tissulaire du plasminogene

Country Status (4)

Country	Link
AU (1)	AU8272887A (fr)
CA (1)	CA1319610C (fr)
PH (1)	PH27178A (fr)
WO (1)	WO1988003030A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1263452A4 (fr) *	2000-02-08	2006-12-20	Univ Northwestern	Procedes et compositions permettant de produire de l'angiostatine

1987
- 1987-10-27 WO PCT/US1987/002755 patent/WO1988003030A1/fr not_active Ceased
- 1987-10-27 AU AU82728/87A patent/AU8272887A/en not_active Abandoned
- 1987-10-29 CA CA000550845A patent/CA1319610C/fr not_active Expired - Fee Related
- 1987-10-30 PH PH36009A patent/PH27178A/en unknown

Also Published As

Publication number	Publication date
WO1988003030A1 (fr)	1988-05-05
PH27178A (en)	1993-04-02
AU8272887A (en)	1988-05-25

Legal Events

Date	Code	Title	Description
1998-06-29	MKLA	Lapsed

Publication	Publication Date	Title
US5500412A (en)	1996-03-19	Thrombin derived polypeptides; compositions and methods for use
Strickland et al.	1976	Studies on the role of plasminogen activator in ovulation. In vitro response of granulosa cells to gonadotropins, cyclic nucleotides, and prostaglandins.
Gross et al.	1983	Increased capillary endothelial cell protease activity in response to angiogenic stimuli in vitro.
Crutchley et al.	1986	Endotoxin induction of an inhibitor of plasminogen activator in bovine pulmonary artery endothelial cells.
JP2766986B2 (ja)	1998-06-18	動脈の血栓症的閉塞または塞栓症を阻止するための医薬組成物
Tuszynski et al.	2002	Angiostatin binds to tyrosine kinase substrate annexin II through the lysine-binding domain in endothelial cells
JPH0378375B2 (fr)	1991-12-13
TWINING et al.	1999	Extrahepatic synthesis of plasminogen in the human cornea is up-regulated by interleukins-1α and-1β
Slivka et al.	1991	Platelets stimulate endothelial cells to synthesize type 1 plasminogen activator inhibitor. Evaluation of the role of transforming growth factor beta
JP2690944B2 (ja)	1997-12-17	組織プラスミノーゲンアクチベーター活性を有するタンパク質の高濃度溶液
JPS61243024A (ja)	1986-10-29	新規化合物、その製法及びそれを含む医薬組成物
Smith et al.	1982	Acyl-enzymes as thrombolytic agents in a rabbit model of venous thrombosis
Wessler et al.	1978	An assay of the antithrombotic action of warfarin: its correlation with the inhibition of stasis thrombosis in rabbits
US4996050A (en)	1991-02-26	Fibrinolytic activity enhancer
ZA200403285B (en)	2005-07-27	Non-neurotoxic plasminogen activating factors for treating stroke.
JP4129994B2 (ja)	2008-08-06	組織因子凝固系インヒビター含有血管新生阻害剤
Fehrenbacher et al.	1979	Synthesis of plasminogen activator by bovine corneal endothelial cells
AU567491B2 (en)	1987-11-26	New fibrionoltic enzymes
Bocci et al.	1973	Factors regulating plasma protein synthesis
JP3980088B2 (ja)	2007-09-19	傷治癒を改善するプラスミノーゲン活性化因子からなる製剤の使用
CA1319610C (fr)	1993-06-29	Methode d'induction de la production endogene de l'activateur tissulaire du plasminogene
JPWO1997035609A1 (ja)	1999-05-18	組織因子凝固系インヒビター含有血管新生阻害剤
EP0251806B1 (fr)	1993-09-22	Production d'un activateur de plasminogène
Laug et al.	1976	The effect of cyclic AMP and prostaglandins on the fibrinolytic activity of mouse neuroblastoma cells
CA1202895A (fr)	1986-04-08	Compose thrombolytique