CA2039248A1 - Preparation ultrapure de thrombine - Google Patents

Preparation ultrapure de thrombine

Info

Publication number: CA2039248A1
Authority: CA; Canada
Prior art keywords: thrombin; supernatant; ultra; pure; protein
Prior art date: 1991-03-27
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.): Abandoned

Application number

CA 2039248

Other languages

English (en)

Inventor

Amal M. Boctor

Surendra C. Mehta

Galen W. Radebaugh

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.)

Warner Lambert Co LLC

Original Assignee

Warner Lambert Co LLC

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.)

1991-03-27

Filing date

1991-03-27

Publication date

1992-09-28

1991-03-27 Application filed by Warner Lambert Co LLC filed Critical Warner Lambert Co LLC

1991-03-27 Priority to CA 2039248 priority Critical patent/CA2039248A1/fr

1991-03-28 Priority claimed from EP91105068A external-priority patent/EP0505604B1/fr

1992-09-28 Publication of CA2039248A1 publication Critical patent/CA2039248A1/fr

Status Abandoned legal-status Critical Current

Links

108090000190 Thrombin Proteins 0.000 title claims abstract description 86
229960004072 thrombin Drugs 0.000 title claims abstract description 82
238000002360 preparation method Methods 0.000 title description 23
230000000694 effects Effects 0.000 claims abstract description 28
238000000034 method Methods 0.000 claims abstract description 17
238000004519 manufacturing process Methods 0.000 claims abstract description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 36
102000004169 proteins and genes Human genes 0.000 claims description 21
108090000623 proteins and genes Proteins 0.000 claims description 21
239000006228 supernatant Substances 0.000 claims description 21
239000011780 sodium chloride Substances 0.000 claims description 20
PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)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)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 claims description 17
108010000499 Thromboplastin Proteins 0.000 claims description 17
102000002262 Thromboplastin Human genes 0.000 claims description 17
239000000203 mixture Substances 0.000 claims description 17
108010094028 Prothrombin Proteins 0.000 claims description 15
102100027378 Prothrombin Human genes 0.000 claims description 15
229940039716 prothrombin Drugs 0.000 claims description 15
239000008363 phosphate buffer Substances 0.000 claims description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
229920000936 Agarose Polymers 0.000 claims description 9
238000005341 cation exchange Methods 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
238000005349 anion exchange Methods 0.000 claims description 6
238000005119 centrifugation Methods 0.000 claims description 6
238000010257 thawing Methods 0.000 claims description 6
230000008014 freezing Effects 0.000 claims description 5
238000007710 freezing Methods 0.000 claims description 5
241000283690 Bos taurus Species 0.000 claims description 4
210000004072 lung Anatomy 0.000 claims description 4
239000000725 suspension Substances 0.000 claims description 4
238000010828 elution Methods 0.000 claims description 3
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
239000002736 nonionic surfactant Substances 0.000 claims description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 23
239000000872 buffer Substances 0.000 description 18
230000035602 clotting Effects 0.000 description 17
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 11
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
239000000463 material Substances 0.000 description 9
206010053567 Coagulopathies Diseases 0.000 description 8
-1 fatty acid esters Chemical class 0.000 description 7
238000002955 isolation Methods 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
229920001223 polyethylene glycol Polymers 0.000 description 6
229920002684 Sepharose Polymers 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
229940088598 enzyme Drugs 0.000 description 4
239000007788 liquid Substances 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
239000000047 product Substances 0.000 description 4
239000012064 sodium phosphate buffer Substances 0.000 description 4
229920002271 DEAE-Sepharose Polymers 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000010452 phosphate Substances 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
238000009010 Bradford assay Methods 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
229920005654 Sephadex Polymers 0.000 description 2
239000012507 Sephadex™ Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
239000000022 bacteriostatic agent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
239000012467 final product Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
150000002989 phenols Chemical class 0.000 description 2
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
229940068968 polysorbate 80 Drugs 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
239000007991 ACES buffer Substances 0.000 description 1
239000007992 BES buffer Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 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
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 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
101100284769 Drosophila melanogaster hemo gene Proteins 0.000 description 1
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 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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
AIKKULXCBHRFOS-UHFFFAOYSA-N Formothion Chemical compound COP(=S)(OC)SCC(=O)N(C)C=O AIKKULXCBHRFOS-UHFFFAOYSA-N 0.000 description 1
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 description 1
108010024636 Glutathione Proteins 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
102000001554 Hemoglobins Human genes 0.000 description 1
108010054147 Hemoglobins Proteins 0.000 description 1
239000007987 MES buffer Substances 0.000 description 1
239000007993 MOPS buffer Substances 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
239000007994 TES buffer Substances 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
239000000654 additive Substances 0.000 description 1
210000000577 adipose tissue Anatomy 0.000 description 1
230000002411 adverse Effects 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
229940030225 antihemorrhagics Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
229960001950 benzethonium chloride Drugs 0.000 description 1
UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 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
230000003115 biocidal effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
230000023555 blood coagulation Effects 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
239000007975 buffered saline Substances 0.000 description 1
229910001424 calcium ion Inorganic materials 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
239000000701 coagulant Substances 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
238000000605 extraction Methods 0.000 description 1
150000002195 fatty ethers Chemical class 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
229940012952 fibrinogen Drugs 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229960003180 glutathione Drugs 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
239000002874 hemostatic agent Substances 0.000 description 1
230000002439 hemostatic effect Effects 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
238000011031 large-scale manufacturing process Methods 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
238000001139 pH measurement Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
229940085991 phosphate ion Drugs 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
238000007694 polyacrylamide gel isoelectric focusing Methods 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000002731 protein assay Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000005057 refrigeration Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
238000001356 surgical 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
229940033663 thimerosal Drugs 0.000 description 1

Landscapes

Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Enzymes And Modification Thereof (AREA)

CA 2039248 1991-03-27 1991-03-27 Preparation ultrapure de thrombine Abandoned CA2039248A1 (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA 2039248 CA2039248A1 (fr)	1991-03-27	1991-03-27	Preparation ultrapure de thrombine

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
CA 2039248 CA2039248A1 (fr)	1991-03-27	1991-03-27	Preparation ultrapure de thrombine
EP91105068A EP0505604B1 (fr)	1991-03-28	1991-03-28	Préparation de thrombine hautement purifié

Publications (1)

Publication Number	Publication Date
CA2039248A1 true CA2039248A1 (fr)	1992-09-28

Family

ID=25674532

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2039248 Abandoned CA2039248A1 (fr)	1991-03-27	1991-03-27	Preparation ultrapure de thrombine

Country Status (1)

Country	Link
CA (1)	CA2039248A1 (fr)

1991
- 1991-03-27 CA CA 2039248 patent/CA2039248A1/fr not_active Abandoned

Publication	Publication Date	Title
US5281528A (en)	1994-01-25	Process for purified thromboplastin for ultra-pure thrombin preparation
US4965203A (en)	1990-10-23	Purified thrombin preparations
EP0221700B1 (fr)	1992-12-30	Préparation à base de thrombine
US4297344A (en)	1981-10-27	Blood coagulation factors and process for their manufacture
US7351561B2 (en)	2008-04-01	Thrombin preparations and process for their production
US6159468A (en)	2000-12-12	Activated protein C formulations
US7473543B2 (en)	2009-01-06	Thrombin compositions
HU180816B (en)	1983-04-29	Process for producing composition from human nlood plasma for improving agglutination of blood
EP2167041A2 (fr)	2010-03-31	Compositions de thrombine stabilisées
JPH01193229A (ja)	1989-08-03	抗血液凝固剤
EP0277096B1 (fr)	1992-07-08	Préparations de thrombine
EP0505604B1 (fr)	1996-09-25	Préparation de thrombine hautement purifié
EP0726076B1 (fr)	2000-08-16	PROCEDE DE STABILISATION DE PROTéINE C ACTIVEE OU NON ACTIVEE ET COMPOSITION STABILISEE
US5525498A (en)	1996-06-11	Process for preparing an ultra-pure thrombin preparation
AU642987B2 (en)	1993-11-04	Ultra-pure thrombin preparation
CA2039248A1 (fr)	1992-09-28	Preparation ultrapure de thrombine
JP3282834B2 (ja)	2002-05-20	超高純度トロンビン調製物
NZ237568A (en)	1992-06-25	Thrombin preparation with a specific activity of from 4000-11000 units per mg of protein
IE75378B1 (en)	1997-09-10	Highly purified thrombin preparation
EP1927658B1 (fr)	2012-10-10	Compositions de thrombine
PT97311B (pt)	1998-08-31	Processo para a preparacao de trombina ultra-pura

Legal Events

Date	Code	Title	Description
1999-03-29	FZDE	Dead