HU217585B - Eljárás inzulin epszilon-aminocsoportjainak szelektív acilezésére - Google Patents
Eljárás inzulin epszilon-aminocsoportjainak szelektív acilezésére Download PDFInfo
- Publication number
- HU217585B HU217585B HU9800566A HU9800566A HU217585B HU 217585 B HU217585 B HU 217585B HU 9800566 A HU9800566 A HU 9800566A HU 9800566 A HU9800566 A HU 9800566A HU 217585 B HU217585 B HU 217585B
- Authority
- HU
- Hungary
- Prior art keywords
- insulin
- reaction
- fatty acid
- mixture
- ester
- Prior art date
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- 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 title claims abstract description 125
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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 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
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- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
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- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229950004152 insulin human Drugs 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 239000011356 non-aqueous organic solvent Substances 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
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
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- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
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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
-
- 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
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9903007A HU9903007D0 (en) | 1994-11-17 | 1995-11-14 | Process for acylation of epsilon-amino groups thereof insulin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/341,231 US5646242A (en) | 1994-11-17 | 1994-11-17 | Selective acylation of epsilon-amino groups |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT77737A HUT77737A (hu) | 1998-07-28 |
| HU217585B true HU217585B (hu) | 2000-02-28 |
Family
ID=23336740
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9800566A HU217585B (hu) | 1994-11-17 | 1995-11-14 | Eljárás inzulin epszilon-aminocsoportjainak szelektív acilezésére |
| HU9903007A HU9903007D0 (en) | 1994-11-17 | 1995-11-14 | Process for acylation of epsilon-amino groups thereof insulin |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9903007A HU9903007D0 (en) | 1994-11-17 | 1995-11-14 | Process for acylation of epsilon-amino groups thereof insulin |
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| SI (1) | SI0712862T1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| GB9316895D0 (en) | 1993-08-13 | 1993-09-29 | Guy S And St Thomas Hospitals | Hepatoselective insulin analogues |
| US6869930B1 (en) * | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| US5951974A (en) * | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
| US6251856B1 (en) | 1995-03-17 | 2001-06-26 | Novo Nordisk A/S | Insulin derivatives |
| US5631347A (en) * | 1995-06-07 | 1997-05-20 | Eli Lilly And Company | Reducing gelation of a fatty acid-acylated protein |
| US6451970B1 (en) * | 1996-02-21 | 2002-09-17 | Novo Nordisk A/S | Peptide derivatives |
| ES2230607T3 (es) * | 1996-07-11 | 2005-05-01 | Novo Nordisk A/S | Metodo selectivo de acilacion. |
| US5905140A (en) * | 1996-07-11 | 1999-05-18 | Novo Nordisk A/S, Novo Alle | Selective acylation method |
| HUP0004169A3 (en) * | 1997-10-24 | 2001-06-28 | Lilly Co Eli | Insoluble insulin compositions and process for production thereof |
| US6444641B1 (en) | 1997-10-24 | 2002-09-03 | Eli Lilly Company | Fatty acid-acylated insulin analogs |
| US5981709A (en) * | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
| US5985263A (en) * | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| US6451974B1 (en) | 1999-03-17 | 2002-09-17 | Novo Nordisk A/S | Method of acylating peptides and novel acylating agents |
| AU4904800A (en) | 1999-05-27 | 2000-12-18 | Robert Z-T. Luo | Identification of compounds for modulating dimeric receptors |
| US7169889B1 (en) | 1999-06-19 | 2007-01-30 | Biocon Limited | Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin |
| JP2003532691A (ja) * | 2000-05-05 | 2003-11-05 | ノボ ノルディスク アクティーゼルスカブ | 重症疾患神経障害 |
| US7316999B2 (en) | 2000-06-02 | 2008-01-08 | Novo Nordisk A/S | Glucose dependent release of insulin from glucose sensing insulin derivatives |
| WO2002051428A1 (en) * | 2000-12-25 | 2002-07-04 | Shiseido Company, Ltd. | Sympathetic-activating perfume composition |
| US7060675B2 (en) * | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| US6867183B2 (en) | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| US7713932B2 (en) | 2001-06-04 | 2010-05-11 | Biocon Limited | Calcitonin drug-oligomer conjugates, and uses thereof |
| US6858580B2 (en) * | 2001-06-04 | 2005-02-22 | Nobex Corporation | Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6713452B2 (en) * | 2001-06-04 | 2004-03-30 | Nobex Corporation | Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6828305B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6828297B2 (en) | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6835802B2 (en) * | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
| BR0211346A (pt) * | 2001-07-24 | 2004-09-21 | Novo Nordisk As | Método para produzir um polipeptìdeo, e, precursor de polipeptìdeo para um polipeptìdeo desejado |
| EP1421102A2 (en) * | 2001-07-24 | 2004-05-26 | Novo Nordisk A/S | Method for making acylated polypeptides |
| US7595172B2 (en) * | 2001-07-24 | 2009-09-29 | Novo Nordisk A/S | Method for making acylated polypeptides |
| US20030082671A1 (en) * | 2001-07-24 | 2003-05-01 | Thomas Hoeg-Jensen | Method for making acylated polypeptides |
| US7196059B2 (en) | 2001-09-07 | 2007-03-27 | Biocon Limited | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| US7166571B2 (en) * | 2001-09-07 | 2007-01-23 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US7030082B2 (en) * | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
| US7312192B2 (en) | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US6913903B2 (en) * | 2001-09-07 | 2005-07-05 | Nobex Corporation | Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| ATE446971T1 (de) | 2001-09-07 | 2009-11-15 | Biocon Ltd | Verfahren zur synthese von insulinpolypeptid- oligomer-konjugaten und proinsulinpolypeptid- oligomer-konjugaten und verfahren zu deren synthese |
| US6770625B2 (en) | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| US20030199445A1 (en) * | 2002-02-07 | 2003-10-23 | Knudsen Lotte Bjerre | Use of GLP-1 compound for treatment of critically ill patients |
| AU2003236521A1 (en) | 2002-06-13 | 2003-12-31 | Nobex Corporation | Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus |
| US7273921B2 (en) | 2002-09-25 | 2007-09-25 | Novo Nordisk A/S | Method for producing acylated peptides |
| WO2004029077A2 (en) * | 2002-09-25 | 2004-04-08 | Novo Nordisk A/S | Method for producing acylated peptides |
| JP4463814B2 (ja) * | 2003-08-05 | 2010-05-19 | ノボ ノルディスク アクティーゼルスカブ | 新規のインスリン誘導体 |
| WO2005047508A1 (en) | 2003-11-14 | 2005-05-26 | Novo Nordisk A/S | Processes for making acylated insulin |
| WO2006014673A2 (en) | 2004-07-19 | 2006-02-09 | Nobex Corporation | Insulin-oligomer conjugates, formulations and uses thereof |
| EP1917363B1 (en) | 2005-08-16 | 2011-06-22 | Novo Nordisk A/S | Method for making mature insulin polypeptides |
| CN101389650B (zh) * | 2005-12-28 | 2012-10-10 | 诺沃-诺迪斯克有限公司 | 包含酰化胰岛素和锌的组合物以及制备所述组合物的方法 |
| DE602007009496D1 (de) | 2006-02-27 | 2010-11-11 | Novo Nordisk As | Insulinderivate |
| WO2007121318A2 (en) * | 2006-04-12 | 2007-10-25 | Emisphere Technologies, Inc. | Formulations for delivering insulin |
| EP2049149B1 (en) | 2006-07-31 | 2015-04-15 | Novo Nordisk A/S | Pegylated extended insulins |
| BRPI0717098B8 (pt) | 2006-09-22 | 2021-05-25 | Novo Nordisk As | análogos de insulina humana resistentes à protease, composição farmacêutica e processo para sua preparação |
| ES2464282T3 (es) | 2006-09-27 | 2014-06-02 | Novo Nordisk A/S | Método para preparar polipéptidos de insulina madura |
| US9387176B2 (en) | 2007-04-30 | 2016-07-12 | Novo Nordisk A/S | Method for drying a protein composition, a dried protein composition and a pharmaceutical composition comprising the dried protein |
| CN101677947B (zh) | 2007-06-13 | 2013-07-17 | 诺沃-诺迪斯克有限公司 | 包含胰岛素衍生物的药物制剂 |
| CN101939023B (zh) | 2007-10-16 | 2016-08-03 | 百康有限公司 | 可经口给药的固体药物组合物及其方法 |
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| US8691759B2 (en) | 2008-03-18 | 2014-04-08 | Novo Nordisk A/S | Protease stabilized, acylated insulin analogues |
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| JP4959005B2 (ja) * | 2008-10-30 | 2012-06-20 | ノボ・ノルデイスク・エー／エス | 毎日の注射頻度より少ないインスリン注射での真性糖尿病の治療 |
| US20120040886A1 (en) * | 2009-02-20 | 2012-02-16 | Zheng Xin Dong | Analogues of Neuropeptide Y Having Proline Substitution At Position 34 |
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| US9896496B2 (en) | 2013-10-07 | 2018-02-20 | Novo Nordisk A/S | Derivative of an insulin analogue |
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| CN105440125B (zh) * | 2015-11-25 | 2019-09-24 | 华润昂德生物药业有限公司 | 地特胰岛素或其类似物的制备方法 |
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| SI3554534T1 (sl) | 2016-12-16 | 2021-09-30 | Novo Nordisk A/S | Farmacevtski sestavki, ki vsebujejo inzulin |
| CN107602437A (zh) * | 2017-08-09 | 2018-01-19 | 上海昂德生物科技有限公司 | 活化酯的制备方法 |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| EP3996679B1 (en) | 2019-07-12 | 2023-09-06 | Novo Nordisk A/S | High concentration insulin formulation |
| CN116874585B (zh) * | 2023-09-06 | 2023-12-15 | 杭州湃肽生化科技有限公司 | 一种地特胰岛素的合成方法 |
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| FR1468831A (fr) * | 1965-10-05 | 1967-02-10 | Roussel Uclaf | Procédé de préparation de nouveaux composés polypeptidiques et produits en résultant |
| DE1902865A1 (de) * | 1968-02-01 | 1969-09-11 | American Home Prod | Substituierte Insulin-Derivate,Verfahren zu ihrer Herstellung und ihre Verwendung in pharmazeutischen Zubereitungen |
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| BE791949A (fr) * | 1971-11-27 | 1973-05-28 | Schering Ag | Derives d'insuline, leur preparation et leur utilisation |
| US3755569A (en) * | 1972-07-25 | 1973-08-28 | American Home Prod | Acyl substituted insulins |
| DE2252157C3 (de) * | 1972-10-25 | 1976-03-18 | Hoechst Ag | Zwischenprodukte zur herstellung von insulin, insulin-analogen und -derivaten und verfahren zur herstellung von insulin, insulin analogen und derivaten |
| DE2253327A1 (de) * | 1972-10-31 | 1974-05-09 | Hoechst Ag | Verfahren zur herstellung von insulin, insulin-analogen und -derivaten |
| NL7314766A (enExample) * | 1972-10-31 | 1974-05-02 | ||
| DE2428412A1 (de) * | 1974-06-12 | 1976-01-15 | Hoechst Ag | Verfahren zur herstellung von insulin, insulin-analogen und -derivaten |
| DE2439296A1 (de) * | 1974-08-16 | 1976-02-26 | Hoechst Ag | Verfahren zur herstellung von insulin, insulin-analogen und -derivaten |
| GB1492997A (en) * | 1976-07-21 | 1977-11-23 | Nat Res Dev | Insulin derivatives |
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| PH25772A (en) * | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
| JPH01254699A (ja) * | 1988-04-05 | 1989-10-11 | Kodama Kk | インスリン誘導体及びその用途 |
| PT93057B (pt) * | 1989-02-09 | 1995-12-29 | Lilly Co Eli | Processo para a preparacao de analogos da insulina |
| AU8091091A (en) * | 1990-07-26 | 1992-02-18 | University Of Iowa Research Foundation, The | Novel drug delivery systems for proteins and peptides using albumin as a carrier molecule |
| US5304473A (en) * | 1991-06-11 | 1994-04-19 | Eli Lilly And Company | A-C-B proinsulin, method of manufacturing and using same, and intermediates in insulin production |
| RU2164520C2 (ru) * | 1993-09-17 | 2001-03-27 | Ново Нордиск А/С | Производное инсулина, растворимая пролонгированная фармацевтическая композиция, способ пролонгирования гипогликемического действия при лечении диабета |
| DE4437604A1 (de) * | 1994-10-21 | 1996-04-25 | Basf Ag | Konjugate aus einem Poly- oder Oligopeptid und einer niedermolekularen lipophilen Verbindung |
| US5905140A (en) | 1996-07-11 | 1999-05-18 | Novo Nordisk A/S, Novo Alle | Selective acylation method |
-
1994
- 1994-11-17 US US08/341,231 patent/US5646242A/en not_active Ceased
-
1995
- 1995-11-14 AT AT95308167T patent/ATE328902T1/de active
- 1995-11-14 AU AU42372/96A patent/AU691066B2/en not_active Revoked
- 1995-11-14 PT PT95308167T patent/PT712862E/pt unknown
- 1995-11-14 JP JP51696396A patent/JP4312828B2/ja not_active Expired - Lifetime
- 1995-11-14 IN IN1452CA1995 patent/IN179820B/en unknown
- 1995-11-14 WO PCT/US1995/014872 patent/WO1996015803A1/en not_active Ceased
- 1995-11-14 IL IL11597295A patent/IL115972A/xx unknown
- 1995-11-14 CZ CZ19971456A patent/CZ287731B6/cs not_active IP Right Cessation
- 1995-11-14 EP EP02000258A patent/EP1227107A1/en not_active Ceased
- 1995-11-14 HU HU9800566A patent/HU217585B/hu not_active IP Right Cessation
- 1995-11-14 YU YU71495A patent/YU71495A/sh unknown
- 1995-11-14 BR BR9509652A patent/BR9509652A/pt not_active Application Discontinuation
- 1995-11-14 RU RU97110075/04A patent/RU2155773C2/ru active
- 1995-11-14 AR ARP950100165A patent/AR003915A1/es not_active Application Discontinuation
- 1995-11-14 NZ NZ297256A patent/NZ297256A/xx active IP Right Revival
- 1995-11-14 EP EP95308167A patent/EP0712862B1/en not_active Expired - Lifetime
- 1995-11-14 CN CN95197224A patent/CN1171742A/zh active Pending
- 1995-11-14 CA CA002205061A patent/CA2205061A1/en not_active Abandoned
- 1995-11-14 DK DK95308167T patent/DK0712862T3/da active
- 1995-11-14 DE DE69535031T patent/DE69535031T2/de not_active Expired - Lifetime
- 1995-11-14 HU HU9903007A patent/HU9903007D0/hu unknown
- 1995-11-14 ZA ZA959680A patent/ZA959680B/xx unknown
- 1995-11-14 TR TR95/01421A patent/TR199501421A2/xx unknown
- 1995-11-14 ES ES95308167T patent/ES2264124T3/es not_active Expired - Lifetime
- 1995-11-14 PL PL95320556A patent/PL320556A1/xx unknown
- 1995-11-14 CO CO95053590A patent/CO4520285A1/es unknown
- 1995-11-14 SI SI9530727T patent/SI0712862T1/sl unknown
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1997
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1998
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