IL99384A - Process for the purification on insulins by chromatography - Google Patents
Process for the purification on insulins by chromatographyInfo
- Publication number
- IL99384A IL99384A IL9938491A IL9938491A IL99384A IL 99384 A IL99384 A IL 99384A IL 9938491 A IL9938491 A IL 9938491A IL 9938491 A IL9938491 A IL 9938491A IL 99384 A IL99384 A IL 99384A
- Authority
- IL
- Israel
- Prior art keywords
- insulin
- buffer
- glycine
- chromatography
- column
- Prior art date
Links
- 102000004877 Insulin Human genes 0.000 title claims abstract description 49
- 108090001061 Insulin Proteins 0.000 title claims abstract description 49
- 239000004026 insulin derivative Substances 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000004587 chromatography analysis Methods 0.000 title claims abstract description 19
- 238000000746 purification Methods 0.000 title claims abstract description 12
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class 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 claims abstract description 94
- 229940125396 insulin Drugs 0.000 claims abstract description 37
- 239000002904 solvent Substances 0.000 claims abstract description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 239000011877 solvent mixture Substances 0.000 claims abstract description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 75
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 41
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 41
- 239000004471 Glycine Substances 0.000 claims description 35
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 15
- 229960003237 betaine Drugs 0.000 claims description 9
- 239000004473 Threonine Substances 0.000 claims description 7
- 229960002898 threonine Drugs 0.000 claims description 7
- 150000008575 L-amino acids Chemical class 0.000 claims description 6
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical group OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 claims description 2
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 2
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 2
- 235000019766 L-Lysine Nutrition 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 2
- 229930064664 L-arginine Natural products 0.000 claims description 2
- 235000014852 L-arginine Nutrition 0.000 claims description 2
- 239000004472 Lysine Substances 0.000 claims description 2
- 229960003767 alanine Drugs 0.000 claims description 2
- 150000001408 amides Chemical group 0.000 claims description 2
- 229940024606 amino acid Drugs 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 150000002148 esters Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 150000002596 lactones Chemical class 0.000 claims description 2
- 125000000962 organic group Chemical group 0.000 claims description 2
- 229960005190 phenylalanine Drugs 0.000 claims description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 56
- 239000000872 buffer Substances 0.000 description 55
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 39
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 23
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 23
- 235000011130 ammonium sulphate Nutrition 0.000 description 23
- 239000000243 solution Substances 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000002594 sorbent Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 238000011084 recovery Methods 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 238000002425 crystallisation Methods 0.000 description 14
- 230000008025 crystallization Effects 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- -1 for example Proteins 0.000 description 12
- 239000011148 porous material Substances 0.000 description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 10
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 10
- 238000010828 elution Methods 0.000 description 10
- 238000005194 fractionation Methods 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 239000001632 sodium acetate Substances 0.000 description 8
- 235000017281 sodium acetate Nutrition 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 239000001509 sodium citrate Substances 0.000 description 7
- 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 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 101000993800 Sus scrofa Insulin Proteins 0.000 description 4
- 239000012062 aqueous buffer Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 238000007257 deesterification reaction Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 230000002608 insulinlike Effects 0.000 description 3
- 229960004592 isopropanol Drugs 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 101001011741 Bos taurus Insulin Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
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- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 2
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- 229910052783 alkali metal Inorganic materials 0.000 description 1
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- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
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- 239000012535 impurity Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000010829 isocratic elution Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000012886 linear function Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
- 238000007056 transamidation reaction Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
-
- 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
- C07K14/575—Hormones
- C07K14/62—Insulins
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4028120A DE4028120C2 (de) | 1990-09-05 | 1990-09-05 | Verfahren zur Reinigung von Insulin und/oder Insulinderivaten |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL99384A0 IL99384A0 (en) | 1992-08-18 |
| IL99384A true IL99384A (en) | 1995-05-26 |
Family
ID=6413631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9938491A IL99384A (en) | 1990-09-05 | 1991-09-03 | Process for the purification on insulins by chromatography |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US5245008A (cs) |
| EP (1) | EP0474213B1 (cs) |
| JP (1) | JP3161770B2 (cs) |
| KR (1) | KR100191699B1 (cs) |
| AT (1) | ATE128145T1 (cs) |
| AU (1) | AU637255B2 (cs) |
| CA (1) | CA2050644C (cs) |
| CZ (1) | CZ283356B6 (cs) |
| DE (2) | DE4028120C2 (cs) |
| DK (1) | DK0474213T3 (cs) |
| ES (1) | ES2078405T3 (cs) |
| FI (1) | FI98216C (cs) |
| GR (1) | GR3017750T3 (cs) |
| HR (1) | HRP940716B1 (cs) |
| HU (1) | HU207100B (cs) |
| IE (1) | IE68956B1 (cs) |
| IL (1) | IL99384A (cs) |
| LT (1) | LT3329B (cs) |
| LV (1) | LV10105B (cs) |
| NO (1) | NO180681C (cs) |
| NZ (1) | NZ239650A (cs) |
| PL (1) | PL168114B1 (cs) |
| PT (1) | PT98864B (cs) |
| RU (1) | RU2037500C1 (cs) |
| SK (1) | SK278099B6 (cs) |
| UA (1) | UA26375A1 (cs) |
| YU (1) | YU147591A (cs) |
| ZA (1) | ZA917006B (cs) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE59208181D1 (de) * | 1991-12-18 | 1997-04-17 | Hoechst Ag | Verfahren zur Gewinnung von insulinhaltigen Lösungen |
| JP3279362B2 (ja) * | 1992-10-05 | 2002-04-30 | 井上 聰一 | 糖尿病判定方法及び糖尿病判定装置 |
| JP3319812B2 (ja) * | 1993-04-05 | 2002-09-03 | 井上 聰一 | リウマチ判定方法及びリウマチ判定装置 |
| US6869930B1 (en) * | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| DE4405179A1 (de) * | 1994-02-18 | 1995-08-24 | Hoechst Ag | Verfahren zur Gewinnung von Insulin mit korrekt verbundenen Cystinbrücken |
| DE19652713C2 (de) * | 1996-12-18 | 2001-11-22 | Aventis Pharma Gmbh | Verfahren zur Reinigung von Insulin und Insulinderivaten durch Chromatographie an stark saurem Kationenaustauscher |
| RU2122549C1 (ru) * | 1997-12-29 | 1998-11-27 | Закрытое акционерное общество "Фосфосорб" | Способ хроматографического выделения и очистки белков, пептидов и их комплексов |
| DE19838097A1 (de) | 1998-08-24 | 2000-03-02 | Hoechst Marion Roussel De Gmbh | Verfahren zur chromatographischen Reinigung von Insulinen |
| US6248683B1 (en) * | 1999-04-07 | 2001-06-19 | Silicycle Inc. | Process for the regeneration of used silica gel |
| US7309581B2 (en) * | 2000-11-01 | 2007-12-18 | Sysmex Corporation | Method of staining, detection and counting bacteria, and a diluent for bacterial stain |
| UA46666C2 (en) * | 2001-12-29 | 2006-01-16 | Omakooe Ltd Liability Company | Method for preparing dosage form of short-term acting insulin |
| UA46668C2 (en) * | 2001-12-29 | 2006-01-16 | Omakooe Ltd Liability Company | Method for preparing combined dosage form of human insulin |
| UA46669C2 (uk) * | 2001-12-29 | 2005-12-15 | Товариство З Обмеженою Відповідальністю "Мако" | Спосіб приготування готової лікарської форми інсуліну пролонгованої дії |
| AU2004228890B2 (en) * | 2003-04-08 | 2010-04-01 | Novo Nordisk A/S | Regeneration of chromatographic stationary phases |
| BRPI0408978B8 (pt) * | 2003-04-08 | 2021-07-27 | Novo Nordisk As | processos para regenerar uma fase estacionária cromatográfica |
| RU2251426C1 (ru) * | 2003-09-18 | 2005-05-10 | Цыганков Владимир Владимирович | Способ получения инсулина из природного источника и инсулин |
| KR101002296B1 (ko) * | 2005-07-06 | 2010-12-20 | 주식회사 코오롱 | 전방향족 폴리아미드 필라멘트의 제조방법 |
| GB0524782D0 (en) * | 2005-12-05 | 2006-01-11 | Chiron Srl | Analysis of samples |
| CN102015762B (zh) * | 2008-02-19 | 2015-03-18 | 百康有限公司 | 获得纯化的生物活性异源蛋白的方法 |
| WO2011021210A1 (en) * | 2009-07-09 | 2011-02-24 | Biocon Limited | A preparative non-linear gradient based chromatographic method and purified products thereof |
| PL2464655T3 (pl) * | 2009-08-11 | 2017-08-31 | Biocon Limited | Procesy chromatograficzne |
| EP2542565A1 (en) | 2010-03-01 | 2013-01-09 | Novo Nordisk A/S | Preparative rp-hplc method for purifying peptides |
| EP2570183A1 (en) * | 2011-09-15 | 2013-03-20 | InstrAction GmbH | Sorbent comprising on its surface an aliphatic unit for the purification of organic molecules |
| WO2016014325A1 (en) | 2014-07-21 | 2016-01-28 | Merck Sharp & Dohme Corp. | Chromatography process for purification of inlsulin and insulin analogs |
| CN115505035B (zh) * | 2022-08-22 | 2023-09-05 | 南京汉欣医药科技有限公司 | 一种司美格鲁肽中间体多肽的纯化方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2629568C3 (de) * | 1976-07-01 | 1981-09-10 | Hoechst Ag, 6000 Frankfurt | Verfahren zur Reinigung von Insulin, seinen Analogen und Derivaten |
| DE3101382A1 (de) * | 1981-01-17 | 1982-09-02 | Hoechst Ag, 6000 Frankfurt | "verfahren zur herstellung von humanisulin oder dessen derivaten aus schweineinsulin oder dessen derivaten" |
| DE3147842A1 (de) * | 1981-12-03 | 1983-06-23 | Hoechst Ag, 6230 Frankfurt | "verfahren zur trennung von gemischen aus insulin, insulinderivaten und gegebenenfalls verunreinigungen" |
| GB2119248A (en) * | 1982-04-28 | 1983-11-16 | John Kenneth Mcmullen | Insulin formulations and method of producing them |
| WO1989001485A1 (en) * | 1987-08-14 | 1989-02-23 | Gebro Broschek Kg | Purification of raw peptides by preparative medium-pressure liquid chromatography |
-
1990
- 1990-09-05 DE DE4028120A patent/DE4028120C2/de not_active Expired - Lifetime
-
1991
- 1991-09-03 IL IL9938491A patent/IL99384A/en not_active IP Right Cessation
- 1991-09-03 NZ NZ239650A patent/NZ239650A/en not_active IP Right Cessation
- 1991-09-03 RU SU915001389A patent/RU2037500C1/ru active
- 1991-09-03 UA UA5001389A patent/UA26375A1/uk unknown
- 1991-09-03 FI FI914150A patent/FI98216C/fi not_active IP Right Cessation
- 1991-09-03 US US07/754,003 patent/US5245008A/en not_active Expired - Lifetime
- 1991-09-04 DK DK91114936.7T patent/DK0474213T3/da active
- 1991-09-04 YU YU147591A patent/YU147591A/sh unknown
- 1991-09-04 JP JP22324291A patent/JP3161770B2/ja not_active Expired - Lifetime
- 1991-09-04 ZA ZA917006A patent/ZA917006B/xx unknown
- 1991-09-04 EP EP91114936A patent/EP0474213B1/de not_active Expired - Lifetime
- 1991-09-04 IE IE311591A patent/IE68956B1/en not_active IP Right Cessation
- 1991-09-04 CZ CS912717A patent/CZ283356B6/cs not_active IP Right Cessation
- 1991-09-04 DE DE59106519T patent/DE59106519D1/de not_active Expired - Lifetime
- 1991-09-04 KR KR1019910015402A patent/KR100191699B1/ko not_active Expired - Lifetime
- 1991-09-04 SK SK2717-91A patent/SK278099B6/sk not_active IP Right Cessation
- 1991-09-04 AU AU83568/91A patent/AU637255B2/en not_active Expired
- 1991-09-04 NO NO913476A patent/NO180681C/no not_active IP Right Cessation
- 1991-09-04 CA CA002050644A patent/CA2050644C/en not_active Expired - Lifetime
- 1991-09-04 PL PL91291616A patent/PL168114B1/pl unknown
- 1991-09-04 PT PT98864A patent/PT98864B/pt not_active IP Right Cessation
- 1991-09-04 ES ES91114936T patent/ES2078405T3/es not_active Expired - Lifetime
- 1991-09-04 AT AT91114936T patent/ATE128145T1/de not_active IP Right Cessation
- 1991-09-05 HU HU912874A patent/HU207100B/hu unknown
-
1993
- 1993-05-04 LV LVP-93-285A patent/LV10105B/lv unknown
- 1993-06-25 LT LTIP713A patent/LT3329B/lt not_active IP Right Cessation
-
1994
- 1994-10-20 HR HRP-1475/91A patent/HRP940716B1/xx not_active IP Right Cessation
-
1995
- 1995-10-16 GR GR950402850T patent/GR3017750T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| KB | Patent renewed | ||
| HP | Change in proprietorship | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| EXP | Patent expired |