BG61231B1 - A method for isolating factor viii - Google Patents

A method for isolating factor viii Download PDF

Info

Publication number: BG61231B1
Authority: BG; Bulgaria
Prior art keywords: factor viii; plasma; volume; gel filtration; gel
Prior art date: 1989-11-09

Application number

BG96316A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG96316A (bg

Inventor

Per Kaersgaard

Original Assignee

Novo Nordisk As

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.)

1989-11-09

Filing date

1992-05-08

Publication date

1997-03-31

1992-05-08 Application filed by Novo Nordisk As filed Critical Novo Nordisk As

1993-12-24 Publication of BG96316A publication Critical patent/BG96316A/bg

1997-03-31 Publication of BG61231B1 publication Critical patent/BG61231B1/bg

Links

229960000301 factor viii Drugs 0.000 title claims abstract description 111
238000000034 method Methods 0.000 title claims abstract description 45
108010054218 Factor VIII Proteins 0.000 claims abstract description 110
102000001690 Factor VIII Human genes 0.000 claims abstract description 110
210000002381 plasma Anatomy 0.000 claims abstract description 76
238000002523 gelfiltration Methods 0.000 claims abstract description 45
238000000926 separation method Methods 0.000 claims abstract description 15
238000005194 fractionation Methods 0.000 claims description 16
102000004506 Blood Proteins Human genes 0.000 claims description 8
108010017384 Blood Proteins Proteins 0.000 claims description 8
239000000945 filler Substances 0.000 claims description 8
239000002245 particle Substances 0.000 claims description 6
238000000746 purification Methods 0.000 claims description 6
238000011097 chromatography purification Methods 0.000 claims description 2
238000004108 freeze drying Methods 0.000 claims description 2
239000007787 solid Substances 0.000 claims description 2
230000035699 permeability Effects 0.000 claims 2
239000003795 chemical substances by application Substances 0.000 claims 1
239000004023 fresh frozen plasma Substances 0.000 claims 1
102000004169 proteins and genes Human genes 0.000 abstract description 34
108090000623 proteins and genes Proteins 0.000 abstract description 34
230000000694 effects Effects 0.000 description 27
229920002684 Sepharose Polymers 0.000 description 19
238000005406 washing Methods 0.000 description 15
239000000872 buffer Substances 0.000 description 14
238000012360 testing method Methods 0.000 description 13
108010047303 von Willebrand Factor Proteins 0.000 description 13
102100036537 von Willebrand factor Human genes 0.000 description 12
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 7
238000002474 experimental method Methods 0.000 description 7
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239000012506 Sephacryl® Substances 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
239000000126 substance Substances 0.000 description 6
108010088880 plasmagel Proteins 0.000 description 5
238000001556 precipitation Methods 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
102000009027 Albumins Human genes 0.000 description 4
108010088751 Albumins Proteins 0.000 description 4
102000004411 Antithrombin III Human genes 0.000 description 4
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229960005348 antithrombin iii Drugs 0.000 description 4
230000035602 clotting Effects 0.000 description 4
229960004222 factor ix Drugs 0.000 description 4
239000007863 gel particle Substances 0.000 description 4
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229960001134 von willebrand factor Drugs 0.000 description 4
102100033312 Alpha-2-macroglobulin Human genes 0.000 description 3
102100022641 Coagulation factor IX Human genes 0.000 description 3
206010053567 Coagulopathies Diseases 0.000 description 3
238000002965 ELISA Methods 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
108010076282 Factor IX Proteins 0.000 description 3
201000003542 Factor VIII deficiency Diseases 0.000 description 3
108010049003 Fibrinogen Proteins 0.000 description 3
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108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 3
101800004937 Protein C Proteins 0.000 description 3
102000017975 Protein C Human genes 0.000 description 3
101800001700 Saposin-D Proteins 0.000 description 3
241000700605 Viruses Species 0.000 description 3
238000003556 assay Methods 0.000 description 3
210000001772 blood platelet Anatomy 0.000 description 3
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000015271 coagulation Effects 0.000 description 3
238000005345 coagulation Methods 0.000 description 3
238000010612 desalination reaction Methods 0.000 description 3
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150000003839 salts Chemical class 0.000 description 3
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
102100026735 Coagulation factor VIII Human genes 0.000 description 2
108010014173 Factor X Proteins 0.000 description 2
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241000283973 Oryctolagus cuniculus Species 0.000 description 2
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238000010257 thawing Methods 0.000 description 2
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208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
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 description 1
101710117545 C protein Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
108010004103 Chylomicrons Proteins 0.000 description 1
229940124135 Factor VIII inhibitor Drugs 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
208000009292 Hemophilia A Diseases 0.000 description 1
208000032843 Hemorrhage Diseases 0.000 description 1
238000011993 High Performance Size Exclusion Chromatography Methods 0.000 description 1
108090000144 Human Proteins Proteins 0.000 description 1
102000003839 Human Proteins Human genes 0.000 description 1
235000003332 Ilex aquifolium Nutrition 0.000 description 1
241000209027 Ilex aquifolium Species 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
108010094028 Prothrombin Proteins 0.000 description 1
102100027378 Prothrombin Human genes 0.000 description 1
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 1
229930006000 Sucrose Natural products 0.000 description 1
108010000499 Thromboplastin Proteins 0.000 description 1
102000002262 Thromboplastin Human genes 0.000 description 1
238000006887 Ullmann reaction Methods 0.000 description 1
239000013543 active substance Substances 0.000 description 1
238000001042 affinity chromatography Methods 0.000 description 1
229940050528 albumin Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
210000000601 blood cell Anatomy 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
239000003114 blood coagulation factor Substances 0.000 description 1
239000012503 blood component Substances 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
239000010839 body fluid Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
238000011088 calibration curve Methods 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003593 chromogenic compound Substances 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000006167 equilibration buffer Substances 0.000 description 1
210000003722 extracellular fluid Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000011010 flushing procedure Methods 0.000 description 1
239000012634 fragment Substances 0.000 description 1
238000005227 gel permeation chromatography Methods 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
238000009499 grossing Methods 0.000 description 1
208000031169 hemorrhagic disease Diseases 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000000951 immunodiffusion Effects 0.000 description 1
238000000760 immunoelectrophoresis Methods 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
229940072221 immunoglobulins Drugs 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
102000013415 peroxidase activity proteins Human genes 0.000 description 1
108040007629 peroxidase activity proteins Proteins 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
238000001470 plasma protein fractionation Methods 0.000 description 1
230000010118 platelet activation Effects 0.000 description 1
239000005373 porous glass Substances 0.000 description 1
238000004321 preservation Methods 0.000 description 1
238000002203 pretreatment Methods 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000000164 protein isolation Methods 0.000 description 1
238000001742 protein purification Methods 0.000 description 1
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
229940039716 prothrombin Drugs 0.000 description 1
238000011002 quantification Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000012898 sample dilution Substances 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000001542 size-exclusion chromatography Methods 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Hematology (AREA)
Gastroenterology & Hepatology (AREA)
Zoology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Toxicology (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Investigating Or Analysing Biological Materials (AREA)
Housing For Livestock And Birds (AREA)
Cephalosporin Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
External Artificial Organs (AREA)
Separation Using Semi-Permeable Membranes (AREA)
Separation By Low-Temperature Treatments (AREA)
Amplifiers (AREA)
Networks Using Active Elements (AREA)

BG96316A 1989-11-09 1992-05-08 A method for isolating factor viii BG61231B1 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DK562189A DK162233C (da)	1989-11-09	1989-11-09	Fremgangsmaade til isolering af faktor viii fra blodplasma og pharmaceutisk praeparat indeholdende den saaledes isolerede fator viii
PCT/DK1990/000279 WO1991007438A1 (en)	1989-11-09	1990-11-05	A method for isolating factor viii

Publications (2)

Publication Number	Publication Date
BG96316A BG96316A (bg)	1993-12-24
BG61231B1 true BG61231B1 (en)	1997-03-31

Family

ID=8144000

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG96316A BG61231B1 (en)	1989-11-09	1992-05-08	A method for isolating factor viii

Country Status (26)

Country	Link
US (1)	US5245014A (no)
EP (1)	EP0524172B1 (no)
JP (1)	JP2509407B2 (no)
CN (1)	CN1044121C (no)
AT (1)	ATE118508T1 (no)
AU (1)	AU631471B2 (no)
BG (1)	BG61231B1 (no)
CA (1)	CA2073012C (no)
CZ (1)	CZ537190A3 (no)
DE (1)	DE69017050T2 (no)
DK (1)	DK162233C (no)
ES (1)	ES2068404T3 (no)
FI (1)	FI103510B1 (no)
HU (1)	HU214905B (no)
IE (1)	IE66836B1 (no)
IL (1)	IL96277A (no)
NO (1)	NO180741C (no)
NZ (1)	NZ236004A (no)
PL (1)	PL164894B1 (no)
PT (1)	PT95830B (no)
RU (1)	RU2055593C1 (no)
SK (1)	SK278640B6 (no)
UA (1)	UA29421C2 (no)
WO (1)	WO1991007438A1 (no)
YU (1)	YU47524B (no)
ZA (1)	ZA908599B (no)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE69002033T2 (de) *	1989-05-24	1993-09-30	Miles Inc	Gelfiltration von wärmebehandeltem Faktor VIII.
US5859204A (en) *	1992-04-07	1999-01-12	Emory University	Modified factor VIII
US5888974A (en) *	1992-04-07	1999-03-30	Emory University	Hybrid human/animal factor VIII
US6180371B1 (en)	1996-06-26	2001-01-30	Emory University	Modified factor VIII
US5659017A (en) *	1995-11-07	1997-08-19	Alpha Therapeutic Corporation	Anion exchange process for the purification of Factor VIII
US7560107B2 (en)	1996-06-26	2009-07-14	Emory University	Modified factor VIII
US6458563B1 (en)	1996-06-26	2002-10-01	Emory University	Modified factor VIII
US6531577B1 (en) *	1997-12-15	2003-03-11	Hemasure Denmark A/S	von Willebrand factor (vWF)-containing preparation, process for preparing vWF-containing preparations, and use of such preparations
US6290527B1 (en) *	1998-07-03	2001-09-18	Nippon Telegraph And Telephone Corp.	Nippon telegraph and telephone corporation
PT1820516E (pt)	1999-02-22	2013-10-31	Baxter Int	Novas formulações de factor viii isentas de albumina
JP2002348300A (ja) *	1999-04-12	2002-12-04	Fujimori Kogyo Co Ltd	血液凝固第ｖｉｉｉ因子および血液凝固第ｖｉｉｉ因子／フォン・ビルブラント因子複合体の精製方法
HUP0303130A2 (hu) *	2001-02-05	2004-01-28	Novo Nordisk Health Care Ag	A VII-es faktor és a VIII-as faktor polipeptidek kombinált alkalmazása és ezeket tartalmazó gyógyszerkészítmények
AUPR638801A0 (en) *	2001-07-13	2001-08-09	Life Therapeutics Limited	Factor viii separation
RU2253475C1 (ru) *	2004-02-02	2005-06-10	Общество с ограниченной ответственностью "Гемоцентр"	Способ получения препарата фактора viii
PT1750733E (pt)	2004-05-03	2014-02-14	Baxter Healthcare Sa	Método de administração de factor viii suíno sem domínio b
WO2006021584A2 (en) *	2004-08-27	2006-03-02	Novo Nordisk Health Care Ag	Purification of factor xiii polypeptides from biological materials
US20060226086A1 (en) *	2005-04-08	2006-10-12	Robinson Thomas C	Centrifuge for blood processing systems
RU2324495C1 (ru) *	2006-08-31	2008-05-20	Федеральное государственное унитарное предприятие "Научно-производственное объединение по медицинским иммунобиологическим препаратам "Микроген" Министерства здравоохранения Российской Федерации	Способ получения препарата фактора свертывания viii крови человека
BRPI0921429B1 (pt) *	2008-11-07	2022-07-12	Takeda Pharmaceutical Company Limited	Formulação farmacêutica liofilizada estável, e, método para preparar um fator liofilizado estável
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1989
- 1989-11-09 DK DK562189A patent/DK162233C/da not_active IP Right Cessation
1990
- 1990-10-26 ZA ZA908599A patent/ZA908599B/xx unknown
- 1990-11-01 SK SK5371-90A patent/SK278640B6/sk unknown
- 1990-11-01 CZ CS905371A patent/CZ537190A3/cs unknown
- 1990-11-05 WO PCT/DK1990/000279 patent/WO1991007438A1/en not_active Ceased
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- 1990-11-05 RU SU905052211A patent/RU2055593C1/ru active
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- 1990-11-07 US US07/610,480 patent/US5245014A/en not_active Expired - Lifetime
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1992
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Also Published As

Publication number	Publication date
SK537190A3 (en)	1997-12-10
NO921839L (no)	1992-07-08
AU6747090A (en)	1991-06-13
RU2055593C1 (ru)	1996-03-10
FI922105A0 (fi)	1992-05-08
SK278640B6 (en)	1997-12-10
CZ537190A3 (cs)	1998-05-13
HU9201551D0 (en)	1992-08-28
JP2509407B2 (ja)	1996-06-19
NO180741B (no)	1997-03-03
NO180741C (no)	1997-06-11
PL164894B1 (pl)	1994-10-31
DK562189D0 (da)	1989-11-09
ZA908599B (en)	1991-07-31
DE69017050D1 (de)	1995-03-23
EP0524172B1 (en)	1995-02-15
JPH05501557A (ja)	1993-03-25
DK162233B (da)	1991-09-30
IE66836B1 (en)	1996-02-07
AU631471B2 (en)	1992-11-26
FI103510B (fi)	1999-07-15
PL287703A1 (en)	1991-12-02
YU47524B (sh)	1995-10-03
FI922105L (fi)	1992-05-08
IL96277A (en)	1995-07-31
BG96316A (bg)	1993-12-24
HU214905B (hu)	1998-07-28
ATE118508T1 (de)	1995-03-15
FI103510B1 (fi)	1999-07-15
WO1991007438A1 (en)	1991-05-30
PT95830B (pt)	1997-11-28
NZ236004A (en)	1991-11-26
UA29421C2 (uk)	2000-11-15
CN1044121C (zh)	1999-07-14
YU210590A (sh)	1993-05-28
PT95830A (pt)	1991-09-30
HUT60511A (en)	1992-09-28
ES2068404T3 (es)	1995-04-16
IE904022A1 (en)	1991-05-22
CN1051732A (zh)	1991-05-29
DK562189A (da)	1991-05-10
DE69017050T2 (de)	1995-06-14
CA2073012A1 (en)	1991-05-10
CA2073012C (en)	1996-03-19
EP0524172A1 (en)	1993-01-27
IL96277A0 (en)	1991-08-16
DK162233C (da)	1992-03-16
NO921839D0 (no)	1992-05-08
US5245014A (en)	1993-09-14

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