CH655949A5 - Verfahren zur herstellung von einem threonin(b30)-ester des humaninsulins, einem salz desselben oder einem metallkomplex desselben, sowie diesen ester und eine verwendung desselben. - Google Patents

Verfahren zur herstellung von einem threonin(b30)-ester des humaninsulins, einem salz desselben oder einem metallkomplex desselben, sowie diesen ester und eine verwendung desselben. Download PDF

Info

Publication number: CH655949A5
Authority: CH; Switzerland
Prior art keywords: gly; leu; ala; insulin; glu
Prior art date: 1980-02-11

Application number

CH910/81A

Other languages

German (de)

English (en)

Inventor

Jan Markussen

Original Assignee

Novo Industri 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.)

1980-02-11

Filing date

1981-02-11

Publication date

1986-05-30

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=8095095&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CH655949(A5) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1981-02-11 Application filed by Novo Industri As filed Critical Novo Industri As

1986-05-30 Publication of CH655949A5 publication Critical patent/CH655949A5/de

Links

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 title claims description 58
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 title claims description 56
101000976075 Homo sapiens Insulin Proteins 0.000 title claims description 53
229960002898 threonine Drugs 0.000 title claims description 42
150000003839 salts Chemical class 0.000 title claims description 12
150000004696 coordination complex Chemical class 0.000 title claims description 5
238000004519 manufacturing process Methods 0.000 title description 7
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Substances 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 description 158
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 110
238000006243 chemical reaction Methods 0.000 claims description 73
238000000034 method Methods 0.000 claims description 64
102000004142 Trypsin Human genes 0.000 claims description 60
108090000631 Trypsin Proteins 0.000 claims description 60
239000012588 trypsin Substances 0.000 claims description 60
102000004877 Insulin Human genes 0.000 claims description 59
108090001061 Insulin Proteins 0.000 claims description 59
229940125396 insulin Drugs 0.000 claims description 57
-1 L-threonine ester Chemical class 0.000 claims description 45
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 42
239000004473 Threonine Substances 0.000 claims description 40
239000000203 mixture Substances 0.000 claims description 32
150000002148 esters Chemical class 0.000 claims description 29
239000011541 reaction mixture Substances 0.000 claims description 29
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
108010076181 Proinsulin Proteins 0.000 claims description 23
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 23
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
229940024606 amino acid Drugs 0.000 claims description 18
235000001014 amino acid Nutrition 0.000 claims description 18
150000001413 amino acids Chemical group 0.000 claims description 18
150000001875 compounds Chemical class 0.000 claims description 15
230000008569 process Effects 0.000 claims description 15
241000282898 Sus scrofa Species 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 14
108010005991 Pork Regular Insulin Proteins 0.000 claims description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000006239 protecting group Chemical group 0.000 claims description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 10
241000282414 Homo sapiens Species 0.000 claims description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 9
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
239000003960 organic solvent Substances 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
108090000765 processed proteins & peptides Chemical group 0.000 claims description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 5
235000004279 alanine Nutrition 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
HHMSPIAOYISBOU-IYQBICMXSA-N insulin rabbit 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](CO)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 HHMSPIAOYISBOU-IYQBICMXSA-N 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
108091005804 Peptidases Proteins 0.000 claims description 4
239000004365 Protease Substances 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
150000007524 organic acids Chemical class 0.000 claims description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
241000590035 Achromobacter lyticus Species 0.000 claims description 3
239000004475 Arginine Substances 0.000 claims description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 3
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
241000283081 Balaenoptera physalus Species 0.000 claims description 2
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 2
241000282693 Cercopithecidae Species 0.000 claims description 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Chemical group NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
239000004472 Lysine Chemical group 0.000 claims description 2
241000009328 Perro Species 0.000 claims description 2
241000283222 Physeter catodon Species 0.000 claims description 2
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 2
239000007853 buffer solution Substances 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
229910001424 calcium ion Inorganic materials 0.000 claims description 2
235000019253 formic acid Nutrition 0.000 claims description 2
239000002798 polar solvent Substances 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
102100027612 Kallikrein-11 Human genes 0.000 claims 3
101710152431 Trypsin-like protease Proteins 0.000 claims 3
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims 3
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims 2
ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
ODWSTKXGQGYHSH-FXQIFTODSA-N Ala-Arg-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O ODWSTKXGQGYHSH-FXQIFTODSA-N 0.000 claims 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims 1
241000282465 Canis Species 0.000 claims 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
210000003608 fece Anatomy 0.000 claims 1
230000008014 freezing Effects 0.000 claims 1
238000007710 freezing Methods 0.000 claims 1
239000012433 hydrogen halide Substances 0.000 claims 1
229910000039 hydrogen halide Inorganic materials 0.000 claims 1
239000000243 solution Substances 0.000 description 57
101000993800 Sus scrofa Insulin Proteins 0.000 description 40
235000011054 acetic acid Nutrition 0.000 description 34
238000004128 high performance liquid chromatography Methods 0.000 description 26
VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 17
239000001639 calcium acetate Substances 0.000 description 17
235000011092 calcium acetate Nutrition 0.000 description 17
229960005147 calcium acetate Drugs 0.000 description 17
238000004458 analytical method Methods 0.000 description 14
102000004169 proteins and genes Human genes 0.000 description 13
108090000623 proteins and genes Proteins 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
235000018102 proteins Nutrition 0.000 description 11
238000005119 centrifugation Methods 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
230000002608 insulinlike Effects 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
229920005654 Sephadex Polymers 0.000 description 7
239000012507 Sephadex™ Substances 0.000 description 7
150000008551 L-threonines Chemical class 0.000 description 6
239000000872 buffer Substances 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000000047 product Substances 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
238000001962 electrophoresis Methods 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
230000008901 benefit Effects 0.000 description 4
238000010828 elution Methods 0.000 description 4
239000000499 gel Substances 0.000 description 4
239000012535 impurity Substances 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
102000000496 Carboxypeptidases A Human genes 0.000 description 3
108010080937 Carboxypeptidases A Proteins 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
102000035195 Peptidases Human genes 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000002585 base Substances 0.000 description 3
239000011521 glass Substances 0.000 description 3
238000011534 incubation Methods 0.000 description 3
239000004026 insulin derivative Substances 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
238000000926 separation method Methods 0.000 description 3
BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
241000282887 Suidae Species 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
125000001980 alanyl group Chemical group 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000011324 bead Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
239000004202 carbamide Substances 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000007979 citrate buffer Substances 0.000 description 2
238000011109 contamination Methods 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
YQDHCCVUYCIGSW-LBPRGKRZSA-N ethyl (2s)-2-benzamido-5-(diaminomethylideneamino)pentanoate Chemical compound NC(=N)NCCC[C@@H](C(=O)OCC)NC(=O)C1=CC=CC=C1 YQDHCCVUYCIGSW-LBPRGKRZSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000011835 investigation Methods 0.000 description 2
238000004255 ion exchange chromatography Methods 0.000 description 2
230000002427 irreversible effect Effects 0.000 description 2
239000002609 medium Substances 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 description 2
229920002401 polyacrylamide Polymers 0.000 description 2
235000019260 propionic acid Nutrition 0.000 description 2
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 2
235000017281 sodium acetate Nutrition 0.000 description 2
229940087562 sodium acetate trihydrate Drugs 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000000758 substrate Substances 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
YZYKBQUWMPUVEN-UHFFFAOYSA-N zafuleptine Chemical compound OC(=O)CCCCCC(C(C)C)NCC1=CC=C(F)C=C1 YZYKBQUWMPUVEN-UHFFFAOYSA-N 0.000 description 2
TWADEBCIPVNACR-ZDUSSCGKSA-N (2s)-2-(n-(4-methylphenyl)sulfonylanilino)propanoic acid Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N([C@@H](C)C(O)=O)C1=CC=CC=C1 TWADEBCIPVNACR-ZDUSSCGKSA-N 0.000 description 1
QNRATNLHPGXHMA-XZHTYLCXSA-N (r)-(6-ethoxyquinolin-4-yl)-[(2s,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]methanol;hydrochloride Chemical compound Cl.C([C@H]([C@H](C1)CC)C2)CN1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OCC)C=C21 QNRATNLHPGXHMA-XZHTYLCXSA-N 0.000 description 1
VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 1
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
101001011741 Bos taurus Insulin Proteins 0.000 description 1
108010075254 C-Peptide Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
241000288906 Primates Species 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
101150046432 Tril gene Proteins 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
239000001166 ammonium sulphate Substances 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
238000005571 anion exchange chromatography Methods 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
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 1
150000004648 butanoic acid derivatives Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
238000005277 cation exchange chromatography Methods 0.000 description 1
BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000012084 conversion product Substances 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
230000000875 corresponding effect Effects 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
230000029087 digestion Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
230000007071 enzymatic hydrolysis Effects 0.000 description 1
238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
235000011167 hydrochloric acid Nutrition 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
150000002431 hydrogen Chemical group 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000002955 isolation Methods 0.000 description 1
TVHCXXXXQNWQLP-DMTCNVIQSA-N methyl (2s,3r)-2-amino-3-hydroxybutanoate Chemical compound COC(=O)[C@@H](N)[C@@H](C)O TVHCXXXXQNWQLP-DMTCNVIQSA-N 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
238000007711 solidification Methods 0.000 description 1
230000008023 solidification Effects 0.000 description 1
241000894007 species Species 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
XASPGLPXANLVTJ-RITPCOANSA-N tert-butyl (2s,3r)-2-amino-3-hydroxybutanoate Chemical compound C[C@@H](O)[C@H](N)C(=O)OC(C)(C)C XASPGLPXANLVTJ-RITPCOANSA-N 0.000 description 1
125000001239 threonyl group Chemical group 0.000 description 1
230000001810 trypsinlike Effects 0.000 description 1
239000003643 water by type Substances 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc 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
- C07K14/575—Hormones
- C07K14/62—Insulins
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Zoology (AREA)
Genetics & Genomics (AREA)
Gastroenterology & Hepatology (AREA)
Endocrinology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Toxicology (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Diabetes (AREA)
Peptides Or Proteins (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Forklifts And Lifting Vehicles (AREA)

CH910/81A 1980-02-11 1981-02-11 Verfahren zur herstellung von einem threonin(b30)-ester des humaninsulins, einem salz desselben oder einem metallkomplex desselben, sowie diesen ester und eine verwendung desselben. CH655949A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DK57480A DK147109C (da)	1980-02-11	1980-02-11	Fremgangsmaade til fremstilling af humant insulin eller humane insulinestere eller et salt eller kompleks deraf

Publications (1)

Publication Number	Publication Date
CH655949A5 true CH655949A5 (de)	1986-05-30

Family

ID=8095095

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH910/81A CH655949A5 (de)	1980-02-11	1981-02-11	Verfahren zur herstellung von einem threonin(b30)-ester des humaninsulins, einem salz desselben oder einem metallkomplex desselben, sowie diesen ester und eine verwendung desselben.

Country Status (19)

Country	Link
JP (1)	JPS56135452A (fr)
AR (1)	AR231277A1 (fr)
AU (1)	AU541528B2 (fr)
BE (1)	BE887480A (fr)
CA (1)	CA1162868A (fr)
CH (1)	CH655949A5 (fr)
DE (1)	DE3104949C2 (fr)
DK (3)	DK147109C (fr)
ES (1)	ES8205858A1 (fr)
FI (1)	FI77876C (fr)
GB (1)	GB2069502B (fr)
GR (1)	GR73844B (fr)
IT (1)	IT1195038B (fr)
NL (1)	NL178797C (fr)
NO (1)	NO156247C (fr)
NZ (1)	NZ196224A (fr)
PT (1)	PT72485B (fr)
SE (2)	SE427025B (fr)
ZA (1)	ZA81898B (fr)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK147437A (en)	1980-02-11	1900-01-01		Process for preparing human insulin or threonine B30 esters of human insulin, or a salt or complex thereof
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"
AU551174B2 (en) *	1981-09-15	1986-04-17	Nordisk Insulinlaboratorium	Enzymatic preparation of human insulin or b-30 esters thereof
DK149824C (da) *	1982-01-22	1987-03-16	Carlsberg Biotechnology Ltd	Fremgangsmaade til enzymatisk udskiftning af b-30 aminosyrer i insuliner
EP0087238A1 (fr) *	1982-02-08	1983-08-31	Biogen N.V.	Méthode de préparation d'insuline humaine à partir d'insuline non-humaine-
DE3209184A1 (de) *	1982-03-13	1983-09-15	Hoechst Ag, 6230 Frankfurt	Verfahren zur umwandlung von praeproinsulinanaloga zu insulinen
NL8201650A (nl) *	1982-04-21	1983-11-16	Akzo Nv	Semisynthetische bereiding van humane insuline.
EP0367302A3 (fr) *	1982-04-23	1991-06-19	Wako Pure Chemical Industries, Ltd.	Procédé pour la semi-synthèse d'insuline humaine protéase I d'Achromobacter réticulée soluble dans l'eau pour sa mise en oeuvre et procédé pour la préparation de celle-ci
DK55183D0 (da) *	1983-02-09	1983-02-09	Nordisk Insulinlab	Fremgangsmade til fremstilling af human insulin
DE3334407A1 (de) *	1983-09-23	1985-04-04	Hoechst Ag, 6230 Frankfurt	In position b 30 modifizierte insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus
DK119785D0 (da) *	1985-03-15	1985-03-15	Nordisk Gentofte	Insulinpraeparat
US5157021A (en) *	1985-03-15	1992-10-20	Novo Nordisk A/S	Insulin derivatives and pharmaceutical preparations containing these derivatives
SE449472B (sv) *	1985-10-15	1987-05-04	Mth Gruppen Ab	Utrustning vid facklager
WO1988006599A1 (fr) *	1987-02-25	1988-09-07	Novo Industri A/S	Nouveaux derives d'insuline
DK134189D0 (da) *	1989-03-20	1989-03-20	Nordisk Gentofte	Insulinforbindelser
FI96503C (fi) *	1994-08-26	1996-07-10	Hymatic Ltd Oy	Menetelmä ja laitteisto maston ohjaamiseksi
WO2005072803A1 (fr)	2004-01-16	2005-08-11	Biodel, Inc.	Dispositif d'administration sublinguale de medicaments
US20080090753A1 (en)	2004-03-12	2008-04-17	Biodel, Inc.	Rapid Acting Injectable Insulin Compositions
US7713929B2 (en)	2006-04-12	2010-05-11	Biodel Inc.	Rapid acting and long acting insulin combination formulations
US8084420B2 (en)	2005-09-29	2011-12-27	Biodel Inc.	Rapid acting and long acting insulin combination formulations
CA2649109A1 (fr)	2006-04-12	2007-10-25	Biodel, Inc.	Formulations de combinaison d'insuline a action prolongee et a action rapide
US9060927B2 (en)	2009-03-03	2015-06-23	Biodel Inc.	Insulin formulations for rapid uptake

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3064479D1 (en) *	1979-04-13	1983-09-08	Shionogi & Co	Process for preparing a b30-threonine insulin
DK147437A (en)	1980-02-11	1900-01-01		Process for preparing human insulin or threonine B30 esters of human insulin, or a salt or complex thereof
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"

0
- DK DK147437D patent/DK147437A/da unknown
1980
- 1980-02-11 DK DK57480A patent/DK147109C/da not_active IP Right Cessation
1981
- 1981-02-09 DK DK54081A patent/DK147437C/da not_active IP Right Cessation
- 1981-02-09 ES ES499238A patent/ES8205858A1/es not_active Expired
- 1981-02-10 SE SE8100926A patent/SE427025B/sv not_active IP Right Cessation
- 1981-02-10 IT IT19620/81A patent/IT1195038B/it active
- 1981-02-10 AR AR284258A patent/AR231277A1/es active
- 1981-02-10 CA CA000370483A patent/CA1162868A/fr not_active Expired
- 1981-02-10 NL NLAANVRAGE8100624,A patent/NL178797C/xx not_active IP Right Cessation
- 1981-02-10 FI FI810385A patent/FI77876C/fi not_active IP Right Cessation
- 1981-02-10 GB GB8104114A patent/GB2069502B/en not_active Expired
- 1981-02-10 PT PT72485A patent/PT72485B/pt not_active IP Right Cessation
- 1981-02-10 NO NO810443A patent/NO156247C/no unknown
- 1981-02-10 SE SE8100928A patent/SE451143B/sv not_active IP Right Cessation
- 1981-02-10 JP JP1758081A patent/JPS56135452A/ja active Granted
- 1981-02-10 NZ NZ196224A patent/NZ196224A/en unknown
- 1981-02-11 AU AU67180/81A patent/AU541528B2/en not_active Ceased
- 1981-02-11 GR GR64097A patent/GR73844B/el unknown
- 1981-02-11 DE DE3104949A patent/DE3104949C2/de not_active Expired
- 1981-02-11 BE BE6/47396A patent/BE887480A/fr not_active IP Right Cessation
- 1981-02-11 ZA ZA00810898A patent/ZA81898B/xx unknown
- 1981-02-11 CH CH910/81A patent/CH655949A5/de not_active IP Right Cessation

Also Published As

Publication number	Publication date
NL178797B (nl)	1985-12-16
NL178797C (nl)	1986-05-16
DK147109C (da)	1986-12-08
IT1195038B (it)	1988-09-28
SE8100928L (sv)	1981-08-12
SE451143B (sv)	1987-09-07
BE887480A (fr)	1981-08-11
IT8119620A0 (it)	1981-02-10
ES499238A0 (es)	1982-08-01
DK147437C (da)	1986-12-08
PT72485A (en)	1981-03-01
DE3104949A1 (de)	1981-11-26
FI77876B (fi)	1989-01-31
DK57480A (da)	1981-08-12
PT72485B (en)	1982-10-14
FI77876C (fi)	1989-05-10
IT8119620A1 (it)	1982-08-10
NO810443L (no)	1981-08-12
AU541528B2 (en)	1985-01-10
GR73844B (fr)	1984-05-07
ZA81898B (en)	1982-03-31
DK147437B (da)	1984-08-06
AR231277A1 (es)	1984-10-31
NL8100624A (nl)	1981-09-01
DK147109B (da)	1984-04-09
DK54081A (da)	1981-08-12
DK147437A (en)	1900-01-01
ES8205858A1 (es)	1982-08-01
DE3104949C2 (de)	1984-04-26
FI810385L (fi)	1981-08-12
JPH0211240B2 (fr)	1990-03-13
GB2069502A (en)	1981-08-26
SE427025B (sv)	1983-02-28
NZ196224A (en)	1984-08-24
GB2069502B (en)	1984-08-08
CA1162868A (fr)	1984-02-28
JPS56135452A (en)	1981-10-22
NO156247C (no)	1987-08-19
SE8100926L (sv)	1982-08-11
NO156247B (no)	1987-05-11
AU6718081A (en)	1981-08-20

Legal Events

Date	Code	Title	Description
1999-10-15	PL	Patent ceased

Publication	Publication Date	Title
CH655949A5 (de)	1986-05-30	Verfahren zur herstellung von einem threonin(b30)-ester des humaninsulins, einem salz desselben oder einem metallkomplex desselben, sowie diesen ester und eine verwendung desselben.
US4343898A (en)	1982-08-10	Process for preparing esters of human insulin
DE19735711C2 (de)	2001-04-26	Verfahren zur Herstellung eines Vorläufers von Insulin oder Insulinderivaten mit korrekt verbundenen Cystinbrücken
EP0056951B1 (fr)	1985-06-19	Procédé de préparation d'insuline humaine ou de ses dérivés à partir d'insuline de porc ou de ses dérivés
EP0140084B1 (fr)	1990-06-13	Procédé pour la préparation de dérivés de l'insuline, dont la chaîne B est allongée en position C-terminale, dérivés de l'insuline modifiés par de la base, composés les contenant et leur utilisation
EP0046979B1 (fr)	1983-09-07	Analogues d'insuline
EP0019115A1 (fr)	1980-11-26	Peptides doués d'activité de pancréozymin-cholécystokinine, procédé de leur préparation et compositions pharmaceutiques les contenant
EP0427162B1 (fr)	1996-05-08	Nouveaux dérivés de l'insuline, leur préparation, leur usage et une composition pharmaceutique les contenant
DE3229674C2 (fr)	1992-07-09
DE3827121A1 (de)	1990-02-15	Verfahren zur herstellung von des-b30-insulinen und des-b30-insulinderivaten
EP0089007B1 (fr)	1986-07-30	Procédé de transformation d'analogues de préproinsulines en insulines
EP0135720A2 (fr)	1985-04-03	Procédé de préparation de dérivés d'insuline
EP0245267B1 (fr)	1990-11-28	Procede de preparation de precurseurs d'insuline contenus dans des melanges de reaction resultant de la preparation de precurseurs d'insuline par pliage des sulfones-s correspondants
DE2518160C2 (fr)	1993-05-06
DE3587226T2 (de)	1993-08-05	Antidiabetikaverbindungen.
LU83197A1 (de)	1981-10-30	Verfahren zur herstellung von threonin b30-estern menschlichen insulins sowie threonin b30-ester menschlichen insulins
DE3687702T2 (de)	1993-06-09	Schutz von methionin in einer polypeptid-kette von irreversibler oxydation.
DE1205546B (de)	1965-11-25	Verfahren zur Herstellung neuer Dekapeptide
CH616651A5 (fr)	1980-04-15
DE1922562B2 (de)	1979-05-31	Verfahren zur Herstellung von Cystinhaltigen Peptiden
DE3837271A1 (de)	1990-05-10	Verfahren zur selektiven spaltung von fusionsproteinen
DE951273C (de)	1956-10-25	Verfahren zur Herstellung von N-acylierten ª‰-Aminoaethylmercaptanen
DE1065424B (de)	1959-09-17	Verfahren zur Herstellung von Pepfiden
DD229398A1 (de)	1985-11-06	Verfahren zur herstellung von amidinohydrazonen mehrfachsubstituierter benzophenone
DE1112525B (de)	1961-08-10	Verfahren zur Herstellung neuer antibiotisch wirksamer cyclischer Dekapeptide aus geradkettigen Penta- oder Dekapeptiden