JPH0569507B2 - - Google Patents
Info
- Publication number
- JPH0569507B2 JPH0569507B2 JP59035894A JP3589484A JPH0569507B2 JP H0569507 B2 JPH0569507 B2 JP H0569507B2 JP 59035894 A JP59035894 A JP 59035894A JP 3589484 A JP3589484 A JP 3589484A JP H0569507 B2 JPH0569507 B2 JP H0569507B2
- Authority
- JP
- Japan
- Prior art keywords
- plasminogen activator
- lysine
- tissue
- present
- solution
- 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
- 102000001938 Plasminogen Activators Human genes 0.000 claims description 21
- 108010001014 Plasminogen Activators Proteins 0.000 claims description 21
- 229940127126 plasminogen activator Drugs 0.000 claims description 21
- 239000004472 Lysine Substances 0.000 claims description 18
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 17
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 17
- 229960000187 tissue plasminogen activator Drugs 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000004090 dissolution Methods 0.000 claims description 4
- 230000009089 cytolysis Effects 0.000 claims 1
- 229960003646 lysine Drugs 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 229920002684 Sepharose Polymers 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 11
- 102000009123 Fibrin Human genes 0.000 description 10
- 108010073385 Fibrin Proteins 0.000 description 10
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 10
- 229950003499 fibrin Drugs 0.000 description 10
- 238000000746 purification Methods 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- 238000004108 freeze drying Methods 0.000 description 6
- 108010088842 Fibrinolysin Proteins 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 230000001605 fetal effect Effects 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 229940012957 plasmin Drugs 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229960005356 urokinase Drugs 0.000 description 5
- 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 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000001840 diploid cell Anatomy 0.000 description 4
- 210000003953 foreskin Anatomy 0.000 description 4
- 238000002523 gelfiltration Methods 0.000 description 4
- 239000012510 hollow fiber Substances 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 102000008946 Fibrinogen Human genes 0.000 description 3
- 108010049003 Fibrinogen Proteins 0.000 description 3
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 3
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000012531 culture fluid Substances 0.000 description 3
- 229940012952 fibrinogen Drugs 0.000 description 3
- 239000003527 fibrinolytic agent Substances 0.000 description 3
- 239000002806 plasmin inhibitor Substances 0.000 description 3
- 229960000103 thrombolytic agent Drugs 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000013566 Plasminogen Human genes 0.000 description 2
- 108010051456 Plasminogen Proteins 0.000 description 2
- 239000012506 Sephacryl® Substances 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000008351 acetate buffer Substances 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000005138 cryopreservation Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 210000000626 ureter Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010062713 Haemorrhagic diathesis Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 description 1
- 102000004407 Lactalbumin Human genes 0.000 description 1
- 108090000942 Lactalbumin Proteins 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 229940122791 Plasmin inhibitor Drugs 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical group NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004246 ligand exchange chromatography Methods 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 229960005337 lysine hydrochloride Drugs 0.000 description 1
- 108010087750 lysyl-plasminogen Proteins 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- -1 sodium nitride Chemical class 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001685 thyroid gland Anatomy 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
- 210000002700 urine Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000003253 viricidal effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Landscapes
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59035894A JPS60181028A (ja) | 1984-02-29 | 1984-02-29 | 組織プラスミノ−ゲン・アクチベ−タ−の溶解補助法 |
| DE8585102058T DE3584902D1 (de) | 1984-02-29 | 1985-02-25 | Waessrige loesung eines darin in erhoehter konzentration aufgeloesten gewebe-plasminogen-aktivators und herstellungsverfahren. |
| EP85102058A EP0156169B1 (fr) | 1984-02-29 | 1985-02-25 | Solution aqueuse d'un activateur tissulaire du plasminogène dissous à une concentration élevée et un procédé d'obtention |
| US06/705,896 US4568544A (en) | 1984-02-29 | 1985-02-26 | Aqueous solution of a tissue plasminogen activator dissolved therein at an increased concentration and a method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59035894A JPS60181028A (ja) | 1984-02-29 | 1984-02-29 | 組織プラスミノ−ゲン・アクチベ−タ−の溶解補助法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60181028A JPS60181028A (ja) | 1985-09-14 |
| JPH0569507B2 true JPH0569507B2 (fr) | 1993-10-01 |
Family
ID=12454730
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59035894A Granted JPS60181028A (ja) | 1984-02-29 | 1984-02-29 | 組織プラスミノ−ゲン・アクチベ−タ−の溶解補助法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60181028A (fr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8513358D0 (en) * | 1985-05-28 | 1985-07-03 | Wellcome Found | Formulation |
| JPH0672105B2 (ja) * | 1985-10-02 | 1994-09-14 | 持田製薬株式会社 | 血栓溶解剤及びその製法 |
| JPS62120321A (ja) * | 1985-11-20 | 1987-06-01 | Eisai Co Ltd | ｔＰＡ含有医薬組成物 |
| DE3718889A1 (de) * | 1987-06-05 | 1988-12-22 | Behringwerke Ag | Verfahren zur herstellung einer loesung hoher spezifischer volumenaktivitaet von einem protein mit gewebe-plasminogenaktivator (t-pa)-aktivitaet, loesung, enthaltend protein mit t-pa-aktivitaet und verwendung der loesung in der human- und veterinaermedizin |
| JP2708749B2 (ja) * | 1987-08-10 | 1998-02-04 | エーザイ株式会社 | 修飾型ｔＰＡ含有注射用組成物 |
| JP2520975B2 (ja) * | 1989-09-21 | 1996-07-31 | 三井東圧化学株式会社 | 組織プラスミノ―ゲンアクチベ―タ―若しくはその誘導体を含有する血栓溶解剤 |
-
1984
- 1984-02-29 JP JP59035894A patent/JPS60181028A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60181028A (ja) | 1985-09-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |