JP6499184B2 - インスリン類似体の新規な誘導体 - Google Patents
インスリン類似体の新規な誘導体 Download PDFInfo
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- JP6499184B2 JP6499184B2 JP2016546167A JP2016546167A JP6499184B2 JP 6499184 B2 JP6499184 B2 JP 6499184B2 JP 2016546167 A JP2016546167 A JP 2016546167A JP 2016546167 A JP2016546167 A JP 2016546167A JP 6499184 B2 JP6499184 B2 JP 6499184B2
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- Prior art keywords
- insulin
- compound
- diabetes
- ethoxy
- once
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- 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 title claims description 234
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000020925 non fasting Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
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- 238000010791 quenching Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 230000003068 static effect Effects 0.000 description 1
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- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- 210000003462 vein Anatomy 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13187626 | 2013-10-07 | ||
| EP13187626.0 | 2013-10-07 | ||
| PCT/EP2014/071236 WO2015052088A1 (en) | 2013-10-07 | 2014-10-03 | Novel derivative of an insulin analogue |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017502074A JP2017502074A (ja) | 2017-01-19 |
| JP2017502074A5 JP2017502074A5 (enExample) | 2017-10-19 |
| JP6499184B2 true JP6499184B2 (ja) | 2019-04-10 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016546167A Expired - Fee Related JP6499184B2 (ja) | 2013-10-07 | 2014-10-03 | インスリン類似体の新規な誘導体 |
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|---|---|
| US (1) | US9896496B2 (enExample) |
| EP (1) | EP3055325B1 (enExample) |
| JP (1) | JP6499184B2 (enExample) |
| KR (1) | KR20160065126A (enExample) |
| CN (1) | CN105636979B (enExample) |
| AU (1) | AU2014333979B2 (enExample) |
| BR (1) | BR112016007166A2 (enExample) |
| CA (1) | CA2926701A1 (enExample) |
| DK (1) | DK3055325T3 (enExample) |
| ES (1) | ES2676065T3 (enExample) |
| HR (1) | HRP20180468T1 (enExample) |
| HU (1) | HUE036702T2 (enExample) |
| IL (1) | IL244507B (enExample) |
| MX (1) | MX366636B (enExample) |
| PL (1) | PL3055325T3 (enExample) |
| PT (1) | PT3055325T (enExample) |
| RS (1) | RS57004B1 (enExample) |
| RU (1) | RU2673185C2 (enExample) |
| SA (1) | SA516370893B1 (enExample) |
| SI (1) | SI3055325T1 (enExample) |
| WO (1) | WO2015052088A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUE032284T2 (en) | 2008-03-18 | 2017-09-28 | Novo Nordisk As | Protease-stabilized, acylated insulin analogues |
| AR105616A1 (es) | 2015-05-07 | 2017-10-25 | Lilly Co Eli | Proteínas de fusión |
| ES2828526T3 (es) | 2016-11-07 | 2021-05-26 | Novo Nordisk As | Esteres activos DCHBS de compuestos PEG y sus usos |
| PE20210857A1 (es) * | 2016-12-16 | 2021-05-18 | Novo Nordisk As | Composiciones farmaceuticas que contienen insulina |
| US11357861B2 (en) | 2017-09-29 | 2022-06-14 | Hanmi Pharm. Co., Ltd | Protein complex comprising non-peptidyl polymer-coupled fatty acid derivative compound as linker and preparation method therefor |
| TWI799680B (zh) * | 2019-01-29 | 2023-04-21 | 美商美國禮來大藥廠 | 製備gip/glp1雙重促效劑之方法 |
| CN111909255A (zh) * | 2019-05-10 | 2020-11-10 | 宁波鲲鹏生物科技有限公司 | 胰岛素衍生物及其制备方法 |
| CN113968911B (zh) | 2020-07-24 | 2023-10-10 | 江苏晟斯生物制药有限公司 | 胰岛素-Fc融合蛋白及其应用 |
| CN115385843A (zh) * | 2021-05-24 | 2022-11-25 | 广东东阳光药业有限公司 | 一种新型的酰化胰岛素类似物 |
| CN117586376A (zh) * | 2022-08-10 | 2024-02-23 | 成都奥达生物科技有限公司 | 一种长效胰岛素化合物 |
| CN117342967A (zh) * | 2023-09-28 | 2024-01-05 | 奥锐特药业(天津)有限公司 | 一种长链脂肪酸化合物的制备方法 |
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|---|---|
| AU2014333979A1 (en) | 2016-03-24 |
| CN105636979A (zh) | 2016-06-01 |
| SI3055325T1 (en) | 2018-05-31 |
| PL3055325T3 (pl) | 2018-06-29 |
| DK3055325T3 (en) | 2018-04-16 |
| RU2016114098A3 (enExample) | 2018-05-21 |
| WO2015052088A1 (en) | 2015-04-16 |
| US9896496B2 (en) | 2018-02-20 |
| BR112016007166A2 (pt) | 2017-09-12 |
| HUE036702T2 (hu) | 2018-07-30 |
| EP3055325B1 (en) | 2018-01-03 |
| RS57004B1 (sr) | 2018-05-31 |
| JP2017502074A (ja) | 2017-01-19 |
| AU2014333979B2 (en) | 2018-02-15 |
| CN105636979B (zh) | 2020-01-10 |
| PT3055325T (pt) | 2018-04-06 |
| IL244507A0 (en) | 2016-04-21 |
| EP3055325A1 (en) | 2016-08-17 |
| KR20160065126A (ko) | 2016-06-08 |
| US20160215037A1 (en) | 2016-07-28 |
| MX2016004325A (es) | 2016-07-11 |
| CA2926701A1 (en) | 2015-04-16 |
| RU2673185C2 (ru) | 2018-11-22 |
| MX366636B (es) | 2019-07-17 |
| HRP20180468T1 (hr) | 2018-05-04 |
| IL244507B (en) | 2018-05-31 |
| SA516370893B1 (ar) | 2018-08-13 |
| ES2676065T3 (es) | 2018-07-16 |
| RU2016114098A (ru) | 2017-11-15 |
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