JPH0369332B2 - - Google Patents
Info
- Publication number
- JPH0369332B2 JPH0369332B2 JP61122049A JP12204986A JPH0369332B2 JP H0369332 B2 JPH0369332 B2 JP H0369332B2 JP 61122049 A JP61122049 A JP 61122049A JP 12204986 A JP12204986 A JP 12204986A JP H0369332 B2 JPH0369332 B2 JP H0369332B2
- Authority
- JP
- Japan
- Prior art keywords
- formulation according
- aqueous solution
- solution
- concentration
- formulation
- 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.)
- Expired - Lifetime
Links
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 77
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 76
- 229960000187 tissue plasminogen activator Drugs 0.000 claims description 76
- 239000000243 solution Substances 0.000 claims description 48
- 239000007864 aqueous solution Substances 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 25
- 238000009472 formulation Methods 0.000 claims description 23
- 208000007536 Thrombosis Diseases 0.000 claims description 16
- 150000001413 amino acids Chemical group 0.000 claims description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 239000011780 sodium chloride Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- 239000012752 auxiliary agent Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- PUUYVMYCMIWHFE-BQBZGAKWSA-N Gly-Ala-Arg Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PUUYVMYCMIWHFE-BQBZGAKWSA-N 0.000 claims description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 2
- 239000008121 dextrose Substances 0.000 claims description 2
- 229960003104 ornithine Drugs 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 210000002966 serum Anatomy 0.000 claims description 2
- 239000004474 valine Substances 0.000 claims description 2
- 108020004511 Recombinant DNA Proteins 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 description 19
- 239000008194 pharmaceutical composition Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 102000001938 Plasminogen Activators Human genes 0.000 description 8
- 108010001014 Plasminogen Activators Proteins 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 8
- 238000001802 infusion Methods 0.000 description 8
- 229940127126 plasminogen activator Drugs 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 238000001291 vacuum drying Methods 0.000 description 6
- 239000012736 aqueous medium Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000012931 lyophilized formulation Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002537 thrombolytic effect Effects 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 101150074155 DHFR gene Proteins 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 description 2
- 108010023197 Streptokinase Proteins 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000020764 fibrinolysis Effects 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 230000003480 fibrinolytic effect Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 102000047823 human PLAT Human genes 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229960005202 streptokinase Drugs 0.000 description 2
- 229960005356 urokinase Drugs 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- 238000012270 DNA recombination Methods 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 235000003332 Ilex aquifolium Nutrition 0.000 description 1
- 235000002296 Ilex sandwicensis Nutrition 0.000 description 1
- 235000002294 Ilex volkensiana Nutrition 0.000 description 1
- 206010023237 Jugular vein thrombosis Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 125000000570 L-alpha-aspartyl group Chemical group [H]OC(=O)C([H])([H])[C@]([H])(N([H])[H])C(*)=O 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229940089206 anhydrous dextrose Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- BRHPBVXVOVMTIQ-ZLELNMGESA-N l-leucine l-leucine Chemical compound CC(C)C[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O BRHPBVXVOVMTIQ-ZLELNMGESA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical group 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000033885 plasminogen activation Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- -1 polyoxyethylene Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035939 shock Effects 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
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8513358 | 1985-05-28 | ||
| GB858513358A GB8513358D0 (en) | 1985-05-28 | 1985-05-28 | Formulation |
| GB8521705 | 1985-08-31 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5230427A Division JPH0759517B2 (ja) | 1985-05-28 | 1993-09-16 | 組織プラスミノーゲン活性化因子含有医薬組成物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6226233A JPS6226233A (ja) | 1987-02-04 |
| JPH0369332B2 true JPH0369332B2 (fr) | 1991-10-31 |
Family
ID=10579735
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61122049A Granted JPS6226233A (ja) | 1985-05-28 | 1986-05-27 | 組織プラスミノ−ゲン活性化因子含有医薬組成物 |
| JP61122050A Granted JPS6226234A (ja) | 1985-05-28 | 1986-05-27 | 非経口溶液製剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61122050A Granted JPS6226234A (ja) | 1985-05-28 | 1986-05-27 | 非経口溶液製剤 |
Country Status (3)
| Country | Link |
|---|---|
| JP (2) | JPS6226233A (fr) |
| GB (1) | GB8513358D0 (fr) |
| ZA (2) | ZA863955B (fr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4929444A (en) * | 1985-05-28 | 1990-05-29 | Burroughs Wellcome Co. | Low pH pharmaceutical formulation containing t-PA |
| JPS62292729A (ja) * | 1986-06-12 | 1987-12-19 | Toyobo Co Ltd | ヒト子宮組織由来プラスミノ−ゲン活性化因子製剤 |
| FI882407A (fi) * | 1987-05-22 | 1988-11-23 | Zymogenetics Inc | Fibrinolytiska proteiner. |
| GB8814604D0 (en) * | 1988-06-20 | 1988-07-27 | Wellcome Found | Medicaments |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5728009A (en) * | 1980-06-11 | 1982-02-15 | Leuven Res & Dev Vzw | Novel plasminogen activator and drug having thrombosis dissolving activity |
| JPS5942321A (ja) * | 1982-05-05 | 1984-03-08 | ジエネンテツク・インコ−ポレイテツド | ヒト組織プラスミノ−ゲン活性化因子 |
| JPS59118717A (ja) * | 1982-12-14 | 1984-07-09 | サウスアフリカン・インヴエンシヨンズ・デイヴエロツプメント・コ−ポレ−シヨン | プラスミノーゲン活性化剤 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60181028A (ja) * | 1984-02-29 | 1985-09-14 | Asahi Chem Ind Co Ltd | 組織プラスミノ−ゲン・アクチベ−タ−の溶解補助法 |
| JPS60184026A (ja) * | 1984-03-01 | 1985-09-19 | Asahi Chem Ind Co Ltd | 組織プラスミノ−ゲン・アクチベ−タ−の溶解補助方法 |
-
1985
- 1985-05-28 GB GB858513358A patent/GB8513358D0/en active Pending
-
1986
- 1986-05-27 JP JP61122049A patent/JPS6226233A/ja active Granted
- 1986-05-27 ZA ZA863955A patent/ZA863955B/xx unknown
- 1986-05-27 ZA ZA863956A patent/ZA863956B/xx unknown
- 1986-05-27 JP JP61122050A patent/JPS6226234A/ja active Granted
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5728009A (en) * | 1980-06-11 | 1982-02-15 | Leuven Res & Dev Vzw | Novel plasminogen activator and drug having thrombosis dissolving activity |
| JPS5942321A (ja) * | 1982-05-05 | 1984-03-08 | ジエネンテツク・インコ−ポレイテツド | ヒト組織プラスミノ−ゲン活性化因子 |
| JPS59118717A (ja) * | 1982-12-14 | 1984-07-09 | サウスアフリカン・インヴエンシヨンズ・デイヴエロツプメント・コ−ポレ−シヨン | プラスミノーゲン活性化剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA863955B (en) | 1988-04-27 |
| GB8513358D0 (en) | 1985-07-03 |
| ZA863956B (en) | 1988-04-27 |
| JPS6226234A (ja) | 1987-02-04 |
| JPS6226233A (ja) | 1987-02-04 |
| JPS6338327B2 (fr) | 1988-07-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1300008C (fr) | Formulation pharmaceutique lyophilisee acide d'activateur du plasminogene tissulaire | |
| CA1297008C (fr) | Solution aqueuse d'activateur tissulaire du plasminogene pour administrationparenterale | |
| EP0875252B1 (fr) | Formulations de protéine C activée | |
| US5407673A (en) | Fibrinolysis and fibrinogenolysis treatment | |
| EP0620738A1 (fr) | Traitement de la fibrinolyse et de la fibrinogenolyse par la plasmine | |
| JPH0672105B2 (ja) | 血栓溶解剤及びその製法 | |
| CA1297010C (fr) | Combinaison de l'activateur tissulaire du plasminogene et d'une prostaglandine | |
| JPH0369332B2 (fr) | ||
| US20050143283A1 (en) | Activated protein c formulations | |
| US5342616A (en) | Method of administering tissue plasminogen activator | |
| JP2907447B2 (ja) | 抗血栓剤 | |
| CA1338551C (fr) | Medicament a base de tpa pour troubles thrombotiques | |
| EP1561469A1 (fr) | Formulations de protéine C activée |