DE2725711A1 - Verfahren zur herstellung von antithrombin iii - Google Patents
Verfahren zur herstellung von antithrombin iiiInfo
- Publication number
- DE2725711A1 DE2725711A1 DE19772725711 DE2725711A DE2725711A1 DE 2725711 A1 DE2725711 A1 DE 2725711A1 DE 19772725711 DE19772725711 DE 19772725711 DE 2725711 A DE2725711 A DE 2725711A DE 2725711 A1 DE2725711 A1 DE 2725711A1
- Authority
- DE
- Germany
- Prior art keywords
- precipitate
- antithrombin iii
- supernatant
- stage
- protein
- 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.)
- Withdrawn
Links
- 102000004411 Antithrombin III Human genes 0.000 title claims description 52
- 108090000935 Antithrombin III Proteins 0.000 title claims description 52
- 229960005348 antithrombin iii Drugs 0.000 title claims description 52
- 238000004519 manufacturing process Methods 0.000 title description 6
- 239000006228 supernatant Substances 0.000 claims description 47
- 210000002381 plasma Anatomy 0.000 claims description 31
- 235000018102 proteins Nutrition 0.000 claims description 31
- 102000004169 proteins and genes Human genes 0.000 claims description 31
- 108090000623 proteins and genes Proteins 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 30
- 238000000926 separation method Methods 0.000 claims description 28
- 108010049003 Fibrinogen Proteins 0.000 claims description 17
- 102000008946 Fibrinogen Human genes 0.000 claims description 17
- 229940012952 fibrinogen Drugs 0.000 claims description 17
- 102100027378 Prothrombin Human genes 0.000 claims description 16
- 108010094028 Prothrombin Proteins 0.000 claims description 16
- 238000001556 precipitation Methods 0.000 claims description 16
- 229940039716 prothrombin Drugs 0.000 claims description 16
- 108010054218 Factor VIII Proteins 0.000 claims description 14
- 102000001690 Factor VIII Human genes 0.000 claims description 14
- 229960000301 factor viii Drugs 0.000 claims description 14
- 229940024546 aluminum hydroxide gel Drugs 0.000 claims description 13
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 claims description 13
- 239000001506 calcium phosphate Substances 0.000 claims description 13
- 239000002244 precipitate Substances 0.000 claims description 13
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 13
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 13
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 13
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 9
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052782 aluminium Inorganic materials 0.000 claims description 4
- 235000004252 protein component Nutrition 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
- 239000002738 chelating agent Substances 0.000 claims description 3
- 230000001376 precipitating effect Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 2
- 229920005682 EO-PO block copolymer Polymers 0.000 claims 4
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 claims 1
- 229920000642 polymer Polymers 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 229920001400 block copolymer Polymers 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 229940001468 citrate Drugs 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 8
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 8
- -1 aluminum ions Chemical class 0.000 description 8
- 102000009027 Albumins Human genes 0.000 description 7
- 108010088751 Albumins Proteins 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000007859 condensation product Substances 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 229920002012 Pluronic® F 38 Polymers 0.000 description 4
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 4
- 229940024545 aluminum hydroxide Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229920001993 poloxamer 188 Polymers 0.000 description 4
- 229920001451 polypropylene glycol Polymers 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 102000006395 Globulins Human genes 0.000 description 3
- 108010044091 Globulins Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- 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 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 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
- 238000005119 centrifugation Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000006920 protein precipitation Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 235000019750 Crude protein Nutrition 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QMHLJNFGMZBHIP-UHFFFAOYSA-N oxirane;propane-1,2-diol Chemical group C1CO1.CC(O)CO QMHLJNFGMZBHIP-UHFFFAOYSA-N 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 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
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 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
- C07K14/81—Protease inhibitors
- C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
- C07K14/8121—Serpins
- C07K14/8128—Antithrombin III
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/827—Proteins from mammals or birds
- Y10S530/829—Blood
- Y10S530/83—Plasma; serum
- Y10S530/831—Cohn fractions
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/694,167 US4087415A (en) | 1976-06-09 | 1976-06-09 | Antithrombin III |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2725711A1 true DE2725711A1 (de) | 1977-12-22 |
Family
ID=24787683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19772725711 Withdrawn DE2725711A1 (de) | 1976-06-09 | 1977-06-07 | Verfahren zur herstellung von antithrombin iii |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US4087415A (enExample) |
| JP (1) | JPS52151710A (enExample) |
| DE (1) | DE2725711A1 (enExample) |
| FR (1) | FR2354340A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0014333A1 (de) * | 1979-01-20 | 1980-08-20 | Biotest-Serum-Institut GmbH | Verfahren zur Herstellung von Fibrinogen, einem die Gerinnungsfaktoren II, VII, IX und X enthaltenden Prothrombinkomplex, Antithrombin III und einer Lösung von lagerstabilen Serumproteinen |
| EP0049861A3 (en) * | 1980-10-09 | 1983-07-27 | Boehringer Mannheim Gmbh | Thrombine inhibitor, its preparation and application |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1603244A (en) * | 1977-05-20 | 1981-11-18 | Max Planck Gesellschaft | Medicaments for the suppression of pathological processes |
| JPS597693B2 (ja) * | 1978-01-07 | 1984-02-20 | 株式会社ミドリ十字 | 抗トロンビン製剤及びその製法 |
| US4170639A (en) * | 1978-07-10 | 1979-10-09 | Warner-Lambert Company | Antihemophilic factor concentrate and its production |
| FR2472390A1 (fr) * | 1979-05-04 | 1981-07-03 | Merieux Inst | Procede de preparation de concentres de complexe prothrombinique hautement purifies, et concentres obtenus |
| SE448945B (sv) * | 1979-12-20 | 1987-03-30 | Blombaeck E G B | Forfarande for rening och /eller koncentrering av faktor viii-komplexet |
| JPS5699422A (en) * | 1980-01-10 | 1981-08-10 | Toyo Soda Mfg Co Ltd | Separation of plasma albumin |
| US4287180A (en) * | 1980-01-28 | 1981-09-01 | Baxter Travenol Laboratories, Inc. | Method for treating blood clotting factor inhibitors |
| US4446314A (en) * | 1980-09-30 | 1984-05-01 | Cutter Laboratories, Inc. | Fractionation of heparin |
| US4386025A (en) * | 1980-09-30 | 1983-05-31 | Cutter Laboratories, Inc. | Method of preparing antithrombin |
| US4517294A (en) * | 1982-03-03 | 1985-05-14 | Genentech, Inc. | Human antithrombin III |
| DE3381783D1 (de) * | 1982-03-03 | 1990-09-13 | Genentech Inc | Menschliches antithrombin iii, dns sequenzen dafuer, expressions- und klonierungsvektoren die solche sequenzen enthalten und damit transformierte zellkulturen, verfahren zur expression von menschlichem antithrombin iii und diese enthaltende pharmazeutische zusammensetzungen. |
| US4632981A (en) * | 1982-07-30 | 1986-12-30 | Genentech, Inc. | Human antithrombin III |
| AT379310B (de) * | 1983-05-20 | 1985-12-27 | Immuno Ag | Verfahren zur herstellung eines antithrombin iii-heparin- bzw. antithrombin iii-heparinoidkonzentrates |
| AU578554B2 (en) * | 1986-01-24 | 1988-10-27 | Japanese Red Cross Society | Centrifugal method of separating blood components |
| EP1117428B1 (en) | 1998-10-08 | 2003-09-24 | Children's Hospital | Compositions and their use for inhibiting angiogenesis |
| SE0203770D0 (sv) * | 2002-12-19 | 2002-12-19 | Biovitrum Ab | Method of separation |
| PT2503995T (pt) * | 2009-11-24 | 2017-11-23 | Grifols Therapeutics Inc | Métodos de liofilização, composições e kits |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3631018A (en) * | 1970-05-01 | 1971-12-28 | Baxter Laboratories Inc | Production of stable high-potency human ahf using polyethylene glycol and glycine to fractionate a cryoprecipitate of ahf concentrate |
| US3682881A (en) * | 1970-10-02 | 1972-08-08 | Baxter Laboratories Inc | Fractionation of plasma using glycine and polyethylene glycol |
| US3770631A (en) * | 1971-06-29 | 1973-11-06 | Baxter Laboratories Inc | Clarification of blood serum and plasma |
| US3839314A (en) * | 1971-06-29 | 1974-10-01 | Baxter Laboratories Inc | Clarification of blood serum and plasma using block copolymers of ethylene oxide and polyoxypropylene |
| SE392038B (sv) * | 1971-09-08 | 1977-03-14 | Kabi Ab | Forfarande for isolering av antitrombin ur blod eller blodprodukter |
| US3956259A (en) * | 1973-01-30 | 1976-05-11 | Baxter Laboratories, Inc. | Fractionation of blood using block copolymer of ethylene oxide and polyoxypropylene polymer to recover fraction suitable for organ perfusate |
| US3880989A (en) * | 1973-01-30 | 1975-04-29 | Baxter Laboratories Inc | Production of antisera comprising fractionating plasma or serum with an ethylene oxide-polyoxypropylene block copolymer |
| US3850903A (en) * | 1973-06-21 | 1974-11-26 | S Mankarious | Plasma volume expander prepared from cohn iv precipitate using block copolymers of ethylene oxide and polyoxypropylene |
-
1976
- 1976-06-09 US US05/694,167 patent/US4087415A/en not_active Expired - Lifetime
-
1977
- 1977-06-06 JP JP6721977A patent/JPS52151710A/ja active Pending
- 1977-06-07 DE DE19772725711 patent/DE2725711A1/de not_active Withdrawn
- 1977-06-09 FR FR7717655A patent/FR2354340A1/fr active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0014333A1 (de) * | 1979-01-20 | 1980-08-20 | Biotest-Serum-Institut GmbH | Verfahren zur Herstellung von Fibrinogen, einem die Gerinnungsfaktoren II, VII, IX und X enthaltenden Prothrombinkomplex, Antithrombin III und einer Lösung von lagerstabilen Serumproteinen |
| EP0049861A3 (en) * | 1980-10-09 | 1983-07-27 | Boehringer Mannheim Gmbh | Thrombine inhibitor, its preparation and application |
Also Published As
| Publication number | Publication date |
|---|---|
| US4087415A (en) | 1978-05-02 |
| JPS52151710A (en) | 1977-12-16 |
| FR2354340B1 (enExample) | 1982-09-10 |
| FR2354340A1 (fr) | 1978-01-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8127 | New person/name/address of the applicant |
Owner name: WILSON, WILLIAM L., 90291 VENICE, CALIF., US BICK, |
|
| 8141 | Disposal/no request for examination |