CA1168583A - Preparation favorisant la coagulation du sang a base de proteines humaines et methode de production - Google Patents
Preparation favorisant la coagulation du sang a base de proteines humaines et methode de productionInfo
- Publication number
- CA1168583A CA1168583A CA000382131A CA382131A CA1168583A CA 1168583 A CA1168583 A CA 1168583A CA 000382131 A CA000382131 A CA 000382131A CA 382131 A CA382131 A CA 382131A CA 1168583 A CA1168583 A CA 1168583A
- Authority
- CA
- Canada
- Prior art keywords
- activity
- preparation
- protein
- factor
- feib
- 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
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 90
- 238000000034 method Methods 0.000 title claims abstract description 40
- 102000003839 Human Proteins Human genes 0.000 title claims abstract description 13
- 108090000144 Human Proteins Proteins 0.000 title claims abstract description 13
- 230000000694 effects Effects 0.000 claims abstract description 98
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 77
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 77
- 108010018823 anti-inhibitor coagulant complex Proteins 0.000 claims abstract description 54
- 229940105776 factor viii inhibitor bypassing activity Drugs 0.000 claims abstract description 54
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims abstract description 12
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims abstract description 12
- 239000003114 blood coagulation factor Substances 0.000 claims abstract description 12
- 235000014633 carbohydrates Nutrition 0.000 claims abstract description 12
- 150000001720 carbohydrates Chemical class 0.000 claims abstract description 12
- 238000010828 elution Methods 0.000 claims abstract description 12
- 229920000642 polymer Polymers 0.000 claims abstract description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 70
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 37
- 108010076282 Factor IX Proteins 0.000 claims description 37
- 229960004222 factor ix Drugs 0.000 claims description 37
- 239000011780 sodium chloride Substances 0.000 claims description 33
- 238000011534 incubation Methods 0.000 claims description 20
- 229920002307 Dextran Polymers 0.000 claims description 19
- 108060005987 Kallikrein Proteins 0.000 claims description 17
- 102000001399 Kallikrein Human genes 0.000 claims description 17
- 150000002500 ions Chemical class 0.000 claims description 17
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 15
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 15
- 108010071241 Factor XIIa Proteins 0.000 claims description 14
- 208000007536 Thrombosis Diseases 0.000 claims description 12
- 108010093564 inter-alpha-inhibitor Proteins 0.000 claims description 12
- 230000002885 thrombogenetic effect Effects 0.000 claims description 11
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 10
- 238000000926 separation method Methods 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 229920000936 Agarose Polymers 0.000 claims description 9
- 230000002950 deficient Effects 0.000 claims description 9
- 230000001939 inductive effect Effects 0.000 claims description 8
- 229940124135 Factor VIII inhibitor Drugs 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 238000005345 coagulation Methods 0.000 claims description 3
- 230000015271 coagulation Effects 0.000 claims description 3
- 108091006629 SLC13A2 Proteins 0.000 claims 1
- 239000000523 sample Substances 0.000 description 22
- 238000010790 dilution Methods 0.000 description 17
- 239000012895 dilution Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- 229920005654 Sephadex Polymers 0.000 description 13
- 239000012507 Sephadex™ Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000012528 membrane Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 210000004379 membrane Anatomy 0.000 description 7
- 239000001509 sodium citrate Substances 0.000 description 7
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 6
- 239000003593 chromogenic compound Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 229920001817 Agar Polymers 0.000 description 5
- 239000005995 Aluminium silicate Substances 0.000 description 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 5
- 239000008272 agar Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000001110 calcium chloride Substances 0.000 description 5
- 229910001628 calcium chloride Inorganic materials 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108090000113 Plasma Kallikrein Proteins 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- 235000012211 aluminium silicate Nutrition 0.000 description 4
- 238000011088 calibration curve Methods 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 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 4
- 239000006228 supernatant Substances 0.000 description 4
- 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 4
- 235000019263 trisodium citrate Nutrition 0.000 description 4
- 229940038773 trisodium citrate Drugs 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 108010048049 Factor IXa Proteins 0.000 description 3
- 108010094028 Prothrombin Proteins 0.000 description 3
- 102100027378 Prothrombin Human genes 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 238000013375 chromatographic separation Methods 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- 230000005684 electric field Effects 0.000 description 3
- 229940067631 phospholipid Drugs 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 229940039716 prothrombin Drugs 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 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 3
- 229960001790 sodium citrate Drugs 0.000 description 3
- 235000011083 sodium citrates Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000013590 bulk material Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 108010074605 gamma-Globulins Proteins 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000013026 undiluted sample Substances 0.000 description 2
- 230000002227 vasoactive effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- ZAMLGGRVTAXBHI-UHFFFAOYSA-N 3-(4-bromophenyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(CC(O)=O)C1=CC=C(Br)C=C1 ZAMLGGRVTAXBHI-UHFFFAOYSA-N 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 201000003542 Factor VIII deficiency Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 229920001499 Heparinoid Polymers 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000009429 hemophilia B Diseases 0.000 description 1
- 239000002554 heparinoid Substances 0.000 description 1
- 229940025770 heparinoids Drugs 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT3781/80 | 1980-07-22 | ||
| AT3781A AT376966B (de) | 1980-01-08 | 1981-01-08 | Verfahren zur herstellung eines furanderivats |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1168583A true CA1168583A (fr) | 1984-06-05 |
Family
ID=3479855
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000382131A Expired CA1168583A (fr) | 1980-07-22 | 1981-07-21 | Preparation favorisant la coagulation du sang a base de proteines humaines et methode de production |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS5928536B2 (fr) |
| CA (1) | CA1168583A (fr) |
-
1981
- 1981-07-21 CA CA000382131A patent/CA1168583A/fr not_active Expired
- 1981-07-21 JP JP56115015A patent/JPS5928536B2/ja not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5753408A (en) | 1982-03-30 |
| JPS5928536B2 (ja) | 1984-07-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |