DE3325223A1 - Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung - Google Patents
Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendungInfo
- Publication number
- DE3325223A1 DE3325223A1 DE19833325223 DE3325223A DE3325223A1 DE 3325223 A1 DE3325223 A1 DE 3325223A1 DE 19833325223 DE19833325223 DE 19833325223 DE 3325223 A DE3325223 A DE 3325223A DE 3325223 A1 DE3325223 A1 DE 3325223A1
- Authority
- DE
- Germany
- Prior art keywords
- proteins
- protein solution
- carbon atoms
- aqueous protein
- aqueous
- 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- Withdrawn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
- 238000000034 method Methods 0.000 title claims abstract description 6
- 239000012460 protein solution Substances 0.000 title claims description 19
- 238000004925 denaturation Methods 0.000 title claims description 7
- 230000036425 denaturation Effects 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title description 3
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 35
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 238000001179 sorption measurement Methods 0.000 claims abstract description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 230000005661 hydrophobic surface Effects 0.000 claims abstract description 4
- 230000008569 process Effects 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- -1 aliphatic radical Chemical class 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 8
- 150000003254 radicals Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 150000005840 aryl radicals Chemical class 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000000108 ultra-filtration Methods 0.000 claims description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 1
- 125000005037 alkyl phenyl group Chemical group 0.000 claims 1
- 230000001516 effect on protein Effects 0.000 claims 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003381 stabilizer Substances 0.000 description 9
- 230000002209 hydrophobic effect Effects 0.000 description 7
- 239000013543 active substance Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 229920001451 polypropylene glycol Polymers 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000036675 Myoglobin Human genes 0.000 description 2
- 108010062374 Myoglobin Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 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
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101001109588 Homo sapiens Polynucleotide 5'-hydroxyl-kinase NOL9 Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 102100022739 Polynucleotide 5'-hydroxyl-kinase NOL9 Human genes 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 241000221535 Pucciniales Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229940050528 albumin Drugs 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 230000008901 benefit Effects 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
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
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- 238000004321 preservation Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- JOWRFSPJFXLGGY-UHFFFAOYSA-N rimazolium Chemical compound C1CCC(C)N2C(=O)C(C(=O)OCC)=C[N+](C)=C21 JOWRFSPJFXLGGY-UHFFFAOYSA-N 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000006228 supernatant Substances 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/41—Porphyrin- or corrin-ring-containing peptides
- A61K38/42—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01023—Beta-galactosidase (3.2.1.23), i.e. exo-(1-->4)-beta-D-galactanase
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Enzymes And Modification Thereof (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Priority Applications (17)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19833325223 DE3325223A1 (de) | 1983-07-13 | 1983-07-13 | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung |
| AT84107889T ATE56876T1 (de) | 1983-07-13 | 1984-07-06 | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung. |
| EP84107889A EP0131864B1 (de) | 1983-07-13 | 1984-07-06 | Gegen Denaturierung beständige, wässrige Proteinlösungen, Verfahren zu ihrer Herstellung und ihre Verwendung |
| DE8484107889T DE3483287D1 (de) | 1983-07-13 | 1984-07-06 | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung. |
| ES534195A ES8600319A1 (es) | 1983-07-13 | 1984-07-11 | Procedimiento para preparar una solucion estable de proteina |
| FI842798A FI80276C (fi) | 1983-07-13 | 1984-07-11 | Mot denaturering skyddade vattenloesningar av proteiner, foerfarande foer deras framstaellning och deras anvaendning. |
| GR75278A GR81504B (enExample) | 1983-07-13 | 1984-07-11 | |
| DK342684A DK168030B1 (da) | 1983-07-13 | 1984-07-12 | Vandige proteinoploesninger, som er bestandige over for denaturering, fremgangsmaade til deres fremstilling og deres anvendelse samt fremgangsmaade til behandling af hydrophobe overflader. |
| IL72389A IL72389A (en) | 1983-07-13 | 1984-07-12 | Aqueous protein solutions which are stable towards denaturing,processes for their preparation and their use |
| JP59143378A JPS6038398A (ja) | 1983-07-13 | 1984-07-12 | 安定な蛋白質水性溶液 |
| IE1796/84A IE57694B1 (en) | 1983-07-13 | 1984-07-12 | Aqueous protein solutions which are stable towards denaturing,processes for their preparation and their use |
| PT78892A PT78892A (de) | 1983-07-13 | 1984-07-12 | Gegen denaturierung bestaendige waessrige proteinloesungen verfahren zu ihrer herstellung und ihre verwendung |
| ZA845384A ZA845384B (en) | 1983-07-13 | 1984-07-12 | Aqueous protein solutions which are stable towards denaturing,processes for their preparation and their use |
| KR1019840004074A KR920002934B1 (ko) | 1983-07-13 | 1984-07-12 | 내변성 단백질 수용액의 제조방법 |
| AU30537/84A AU579106B2 (en) | 1983-07-13 | 1984-07-12 | Aqueous protein solutions which are stable towards denaturing, processes for their preparation and their use |
| ES535482A ES8609361A1 (es) | 1983-07-13 | 1984-08-29 | Procedimiento para tratar superficies hidrofobas para la supresion de su efecto adsorbente y desnaturalizante sobre proteinas |
| US06/825,965 US4637834A (en) | 1983-07-13 | 1986-02-05 | Aqueous protein solutions which are stable towards denaturing, processes for their preparation and their use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19833325223 DE3325223A1 (de) | 1983-07-13 | 1983-07-13 | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3325223A1 true DE3325223A1 (de) | 1985-01-24 |
Family
ID=6203842
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19833325223 Withdrawn DE3325223A1 (de) | 1983-07-13 | 1983-07-13 | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung |
| DE8484107889T Expired - Lifetime DE3483287D1 (de) | 1983-07-13 | 1984-07-06 | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE8484107889T Expired - Lifetime DE3483287D1 (de) | 1983-07-13 | 1984-07-06 | Gegen denaturierung bestaendige, waessrige proteinloesungen, verfahren zu ihrer herstellung und ihre verwendung. |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4637834A (enExample) |
| EP (1) | EP0131864B1 (enExample) |
| JP (1) | JPS6038398A (enExample) |
| KR (1) | KR920002934B1 (enExample) |
| AT (1) | ATE56876T1 (enExample) |
| AU (1) | AU579106B2 (enExample) |
| DE (2) | DE3325223A1 (enExample) |
| DK (1) | DK168030B1 (enExample) |
| ES (2) | ES8600319A1 (enExample) |
| FI (1) | FI80276C (enExample) |
| GR (1) | GR81504B (enExample) |
| IE (1) | IE57694B1 (enExample) |
| IL (1) | IL72389A (enExample) |
| PT (1) | PT78892A (enExample) |
| ZA (1) | ZA845384B (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5004605A (en) * | 1987-12-10 | 1991-04-02 | Cetus Corporation | Low pH pharmaceutical compositions of recombinant β-interferon |
| US5078997A (en) * | 1988-07-13 | 1992-01-07 | Cetus Corporation | Pharmaceutical composition for interleukin-2 containing physiologically compatible stabilizers |
| US5183746A (en) * | 1986-10-27 | 1993-02-02 | Schering Aktiengesellschaft | Formulation processes for pharmaceutical compositions of recombinant β- |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3064888D1 (en) * | 1979-04-30 | 1983-10-27 | Hoechst Ag | Aqueous solutions of proteins stable against denaturization, process for their manufacture, and their utilization |
| JPS61277633A (ja) * | 1985-05-31 | 1986-12-08 | Toray Ind Inc | インタ−フエロン組成物 |
| US4956274A (en) * | 1987-04-06 | 1990-09-11 | Microgenics Corporation | Reagent stabilization in enzyme-donor and acceptor assay |
| US5763394A (en) * | 1988-04-15 | 1998-06-09 | Genentech, Inc. | Human growth hormone aqueous formulation |
| US5981485A (en) * | 1997-07-14 | 1999-11-09 | Genentech, Inc. | Human growth hormone aqueous formulation |
| US5945098A (en) * | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
| US5830452A (en) * | 1990-11-20 | 1998-11-03 | Chiron Corporation | Method for enhancing the anti-tumor therapeutic index of interleukin-2 |
| WO1993019773A1 (en) * | 1992-04-07 | 1993-10-14 | Pitman-Moore, Inc. | Lyophilized somatotropin formulations |
| ES2153385T5 (es) † | 1992-07-31 | 2008-09-01 | Genentech, Inc. | Composicion acuosa a base de hormona del crecimiento humana. |
| JPH11514334A (ja) * | 1995-06-07 | 1999-12-07 | チロン コーポレーション | タンパク質の可溶化、精製、および再生の方法 |
| US6790439B1 (en) | 1995-06-07 | 2004-09-14 | Zymogenetics, Inc. | Thrombopoietin compositions |
| MX9602398A (es) * | 1995-06-23 | 1997-02-28 | Kimberly Clark Co | Material polimerico modificado teniendo humectabilidad mejorada. |
| AUPN801296A0 (en) * | 1996-02-12 | 1996-03-07 | Csl Limited | Stabilised growth hormone formulation and method of preparation thereof |
| MXPA02000404A (es) * | 1999-07-12 | 2004-05-21 | Grandis Biotech Gmbh | Formulaciones de hormona de crecimiento. |
| EP1536835A1 (en) * | 2002-07-09 | 2005-06-08 | Sandoz AG | Liquid formulations with high concentration of human growth hormone (hgh) comprising phenol |
| JP4522997B2 (ja) * | 2003-08-13 | 2010-08-11 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | Ｔｆｐｉおよびｔｆｐｉアナログを精製するための改良された方法 |
| UA89781C2 (uk) | 2004-04-07 | 2010-03-10 | Арес Трейдінг С.А. | Рідкий склад гормона росту |
| EP1847830A1 (en) * | 2006-04-20 | 2007-10-24 | TF Instruments, Inc. | Determining optimal concentrations of protective additives for biomolecules |
| WO2024133849A1 (en) * | 2022-12-22 | 2024-06-27 | The Protein Brewery B.V. | Ovalbumin fermentation |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4439355A (en) * | 1976-12-02 | 1984-03-27 | Colgate-Palmolive Company | Elastic detergent product of improved foaming power after use |
| DE2917535C2 (de) * | 1979-04-30 | 1986-10-30 | Hoechst Ag, 6230 Frankfurt | Gegen Denaturierung beständige Insulinlösungen |
| DE3064888D1 (en) * | 1979-04-30 | 1983-10-27 | Hoechst Ag | Aqueous solutions of proteins stable against denaturization, process for their manufacture, and their utilization |
| JPS58501125A (ja) * | 1981-07-17 | 1983-07-14 | ノルデイスク・インスリンラボラトリウム | 安定な水性治療性インシユリン製剤及びその製造方法 |
-
1983
- 1983-07-13 DE DE19833325223 patent/DE3325223A1/de not_active Withdrawn
-
1984
- 1984-07-06 EP EP84107889A patent/EP0131864B1/de not_active Expired - Lifetime
- 1984-07-06 AT AT84107889T patent/ATE56876T1/de not_active IP Right Cessation
- 1984-07-06 DE DE8484107889T patent/DE3483287D1/de not_active Expired - Lifetime
- 1984-07-11 FI FI842798A patent/FI80276C/fi not_active IP Right Cessation
- 1984-07-11 ES ES534195A patent/ES8600319A1/es not_active Expired
- 1984-07-11 GR GR75278A patent/GR81504B/el unknown
- 1984-07-12 IL IL72389A patent/IL72389A/xx not_active IP Right Cessation
- 1984-07-12 DK DK342684A patent/DK168030B1/da not_active IP Right Cessation
- 1984-07-12 ZA ZA845384A patent/ZA845384B/xx unknown
- 1984-07-12 KR KR1019840004074A patent/KR920002934B1/ko not_active Expired
- 1984-07-12 IE IE1796/84A patent/IE57694B1/en not_active IP Right Cessation
- 1984-07-12 JP JP59143378A patent/JPS6038398A/ja active Granted
- 1984-07-12 AU AU30537/84A patent/AU579106B2/en not_active Expired
- 1984-07-12 PT PT78892A patent/PT78892A/pt active IP Right Revival
- 1984-08-29 ES ES535482A patent/ES8609361A1/es not_active Expired
-
1986
- 1986-02-05 US US06/825,965 patent/US4637834A/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5183746A (en) * | 1986-10-27 | 1993-02-02 | Schering Aktiengesellschaft | Formulation processes for pharmaceutical compositions of recombinant β- |
| US5004605A (en) * | 1987-12-10 | 1991-04-02 | Cetus Corporation | Low pH pharmaceutical compositions of recombinant β-interferon |
| US5078997A (en) * | 1988-07-13 | 1992-01-07 | Cetus Corporation | Pharmaceutical composition for interleukin-2 containing physiologically compatible stabilizers |
Also Published As
| Publication number | Publication date |
|---|---|
| ES535482A0 (es) | 1986-09-01 |
| ES534195A0 (es) | 1985-10-01 |
| DK168030B1 (da) | 1994-01-24 |
| JPH0582397B2 (enExample) | 1993-11-18 |
| IL72389A0 (en) | 1984-11-30 |
| KR850000971A (ko) | 1985-03-14 |
| EP0131864A3 (en) | 1987-08-26 |
| US4637834A (en) | 1987-01-20 |
| FI80276C (fi) | 1990-05-10 |
| AU3053784A (en) | 1985-01-17 |
| IL72389A (en) | 1988-11-30 |
| FI842798A7 (fi) | 1985-01-14 |
| IE841796L (en) | 1985-01-13 |
| PT78892A (de) | 1984-08-01 |
| JPS6038398A (ja) | 1985-02-27 |
| DK342684A (da) | 1985-01-14 |
| DE3483287D1 (de) | 1990-10-31 |
| GR81504B (enExample) | 1984-12-11 |
| FI842798A0 (fi) | 1984-07-11 |
| DK342684D0 (da) | 1984-07-12 |
| ES8600319A1 (es) | 1985-10-01 |
| FI80276B (fi) | 1990-01-31 |
| IE57694B1 (en) | 1993-03-10 |
| ATE56876T1 (de) | 1990-10-15 |
| ES8609361A1 (es) | 1986-09-01 |
| KR920002934B1 (ko) | 1992-04-10 |
| EP0131864B1 (de) | 1990-09-26 |
| EP0131864A2 (de) | 1985-01-23 |
| ZA845384B (en) | 1985-02-27 |
| AU579106B2 (en) | 1988-11-17 |
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| 8139 | Disposal/non-payment of the annual fee |