NO323137B1 - Nye peptidforbindelser som er analoger av glukagon-lignende-peptid-1 (7-37), fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende disse - Google Patents
Nye peptidforbindelser som er analoger av glukagon-lignende-peptid-1 (7-37), fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende disse Download PDFInfo
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- NO323137B1 NO323137B1 NO19991199A NO991199A NO323137B1 NO 323137 B1 NO323137 B1 NO 323137B1 NO 19991199 A NO19991199 A NO 19991199A NO 991199 A NO991199 A NO 991199A NO 323137 B1 NO323137 B1 NO 323137B1
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
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- Life Sciences & Earth Sciences (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9804559A FR2777283B1 (fr) | 1998-04-10 | 1998-04-10 | Nouveaux composes peptidiques analogues du glucagon-peptide- 1 (7-37), leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO991199D0 NO991199D0 (no) | 1999-03-11 |
| NO991199L NO991199L (no) | 1999-10-11 |
| NO323137B1 true NO323137B1 (no) | 2007-01-08 |
Family
ID=9525150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19991199A NO323137B1 (no) | 1998-04-10 | 1999-03-11 | Nye peptidforbindelser som er analoger av glukagon-lignende-peptid-1 (7-37), fremgangsmate ved deres fremstilling og farmasoytiske sammensetninger inneholdende disse |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6620910B1 (da) |
| EP (1) | EP0955314B1 (da) |
| JP (1) | JP3787242B2 (da) |
| CN (1) | CN1305897C (da) |
| AT (1) | ATE255596T1 (da) |
| AU (1) | AU761652B2 (da) |
| BR (1) | BR9902014A (da) |
| CA (1) | CA2263059A1 (da) |
| DE (1) | DE69913242T2 (da) |
| DK (1) | DK0955314T3 (da) |
| ES (1) | ES2212485T3 (da) |
| FR (1) | FR2777283B1 (da) |
| HU (1) | HUP9900604A3 (da) |
| NO (1) | NO323137B1 (da) |
| NZ (1) | NZ334379A (da) |
| PL (1) | PL331960A1 (da) |
| PT (1) | PT955314E (da) |
| ZA (1) | ZA992035B (da) |
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7048906B2 (en) | 1995-05-17 | 2006-05-23 | Cedars-Sinai Medical Center | Methods of diagnosing and treating small intestinal bacterial overgrowth (SIBO) and SIBO-related conditions |
| DE69922043T2 (de) * | 1998-12-07 | 2005-11-24 | Société de Conseils de Recherches et d'Applications Scientifiques S.A.S. | Glp-1 analoge |
| JP2002538081A (ja) | 1998-12-07 | 2002-11-12 | ソシエテ・ドゥ・コンセイユ・ドゥ・ルシェルシュ・エ・ダプリカーション・シャンティフィック・エス・ア・エス | Glp−1の類似体 |
| US9006175B2 (en) | 1999-06-29 | 2015-04-14 | Mannkind Corporation | Potentiation of glucose elimination |
| US7186683B2 (en) | 2000-09-18 | 2007-03-06 | Sanos Bioscience A/S | Use of GLP for the treatment, prevention, diagnosis, and prognosis of bone-related and nutrition-related disorders |
| US7371721B2 (en) | 2000-09-18 | 2008-05-13 | Sanos Bioscience A/S | Use of GLP-2 and related compounds for the treatment, prevention, diagnosis, and prognosis of bone-related disorders and calcium homeostasis related syndromes |
| ES2310192T3 (es) * | 2000-09-18 | 2009-01-01 | Sanos Bioscience A/S | Uso de peptidos glp-2. |
| GB0121709D0 (en) * | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
| KR100989647B1 (ko) | 2001-09-24 | 2010-10-26 | 오레곤 헬스 앤드 사이언스 유니버시티 | 식습관의 변화 |
| US7238671B2 (en) | 2001-10-18 | 2007-07-03 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| CA2463908A1 (en) | 2001-10-18 | 2003-04-24 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| US7332819B2 (en) * | 2002-01-09 | 2008-02-19 | Micron Technology, Inc. | Stacked die in die BGA package |
| US8058233B2 (en) * | 2002-01-10 | 2011-11-15 | Oregon Health And Science University | Modification of feeding behavior using PYY and GLP-1 |
| EP1474163A2 (en) | 2002-01-10 | 2004-11-10 | Imperial College Innovations Limited | Modification of feeding behavior |
| US6923175B2 (en) | 2002-03-20 | 2005-08-02 | Mannkind Corporation | Inhalation apparatus |
| US20080260838A1 (en) * | 2003-08-01 | 2008-10-23 | Mannkind Corporation | Glucagon-like peptide 1 (glp-1) pharmaceutical formulations |
| GB0300571D0 (en) * | 2003-01-10 | 2003-02-12 | Imp College Innovations Ltd | Modification of feeding behaviour |
| JP2007524579A (ja) * | 2003-02-19 | 2007-08-30 | ソシエテ・ドゥ・コンセイユ・ドゥ・ルシェルシュ・エ・ダプリカーション・シャンティフィック・エス・ア・エス | Glp−1の類似体 |
| US7550590B2 (en) | 2003-03-25 | 2009-06-23 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7169926B1 (en) | 2003-08-13 | 2007-01-30 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7678909B1 (en) | 2003-08-13 | 2010-03-16 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| KR20060041309A (ko) | 2003-08-13 | 2006-05-11 | 다케다 야쿠힌 고교 가부시키가이샤 | 4-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도 |
| US7790734B2 (en) | 2003-09-08 | 2010-09-07 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| EP1711523B1 (en) * | 2003-12-16 | 2012-10-10 | Ipsen Pharma | Analogues of glp-1 |
| US7521527B2 (en) | 2003-12-16 | 2009-04-21 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | GLP-1 pharmaceutical compositions |
| US7732446B1 (en) | 2004-03-11 | 2010-06-08 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| CN102127057A (zh) | 2004-03-15 | 2011-07-20 | 武田药品工业株式会社 | 二肽基肽酶抑制剂 |
| JP2008501714A (ja) | 2004-06-04 | 2008-01-24 | 武田薬品工業株式会社 | ジペプチジルペプチダーゼインヒビター |
| WO2006019965A2 (en) | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| ATE486064T1 (de) | 2004-08-20 | 2010-11-15 | Mannkind Corp | Katalyse der diketopiperazinsynthese |
| KR20130066695A (ko) | 2004-08-23 | 2013-06-20 | 맨카인드 코포레이션 | 약물 전달용 디케토피페라진염, 디케토모르포린염 또는 디케토디옥산염 |
| WO2006068978A2 (en) | 2004-12-21 | 2006-06-29 | Takeda Pharmaceutial Company Limited | Dipeptidyl peptidase inhibitors |
| TW200643033A (en) * | 2005-03-08 | 2006-12-16 | Chugai Pharmaceutical Co Ltd | Conjugate of water-soluble modified hyaluronic acid and glp-1 analogue |
| GB0511986D0 (en) * | 2005-06-13 | 2005-07-20 | Imp College Innovations Ltd | Novel compounds and their effects on feeding behaviour |
| MX373000B (es) | 2005-09-14 | 2020-05-21 | Mannkind Corp | Metodo para formulacion de farmaco basado en el aumento de la afinidad de agentes activos hacia las superficies de microparticulas cristalinas. |
| GEP20135838B (en) | 2005-09-14 | 2013-06-10 | Takeda Pharmaceutical | Dipeptidyl peptidase inhibitors usage at diabetes treatment |
| CN101360723A (zh) | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | 制备嘧啶二酮衍生物的方法 |
| EP1943275B1 (en) * | 2005-11-01 | 2010-06-16 | Activotec SPP Limited | Insulinotropic compounds and uses thereof |
| GB0522295D0 (en) * | 2005-11-01 | 2005-12-07 | Activotec Spp Ltd | Peptides and uses thereof |
| EP1986679B1 (en) | 2006-02-22 | 2017-10-25 | MannKind Corporation | A method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent |
| CN1982336B (zh) * | 2006-03-03 | 2011-01-12 | 华东师范大学 | 一种人胰高血糖素样肽-1衍生物及其制备和应用 |
| US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| TWI428346B (zh) | 2006-12-13 | 2014-03-01 | Imp Innovations Ltd | 新穎化合物及其等對進食行為影響 |
| US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| GB2448895A (en) * | 2007-05-01 | 2008-11-05 | Activotec Spp Ltd | GLP-1 like compounds and uses thereof |
| EP2211842B1 (en) * | 2007-10-24 | 2015-08-12 | MannKind Corporation | An inhalable dry powder formulation comprising glp-1 for use in the treatment of hyperglycemia and diabetes by pulmonary administration |
| US8485180B2 (en) | 2008-06-13 | 2013-07-16 | Mannkind Corporation | Dry powder drug delivery system |
| CN101827626B (zh) | 2008-06-13 | 2015-03-18 | 曼金德公司 | 干粉吸入器和用于药物输送的系统 |
| ES2421385T3 (es) | 2008-06-20 | 2013-09-02 | Mannkind Corp | Aparato interactivo y procedimiento para establecer el perfil, en tiempo real, de esfuerzos de inhalación |
| TWI532497B (zh) | 2008-08-11 | 2016-05-11 | 曼凱公司 | 超快起作用胰島素之用途 |
| US8314106B2 (en) | 2008-12-29 | 2012-11-20 | Mannkind Corporation | Substituted diketopiperazine analogs for use as drug delivery agents |
| CN101463081B (zh) * | 2009-01-12 | 2012-07-04 | 华东师范大学 | 一种glp-1衍生物 |
| DK2405963T3 (da) | 2009-03-11 | 2013-12-16 | Mannkind Corp | Apparat, system og fremgangsmåde til at måle modstand i en inhalator |
| WO2010120476A2 (en) * | 2009-04-01 | 2010-10-21 | Amylin Pharmaceuticals, Inc. | N-terminus conformationally constrained glp-1 receptor agonist compounds |
| KR102584844B1 (ko) | 2009-06-12 | 2023-10-04 | 맨카인드 코포레이션 | 한정된 비표면적을 갖는 디케토피페라진 마이크로입자 |
| CA2778698A1 (en) | 2009-11-03 | 2011-05-12 | Mannkind Corporation | An apparatus and method for simulating inhalation efforts |
| CN102985125A (zh) | 2010-06-21 | 2013-03-20 | 曼金德公司 | 干粉药物输送系统和方法 |
| CA2806749A1 (en) | 2010-07-28 | 2012-02-02 | Amylin Pharmaceuticals, Llc | Glp-1 receptor agonist compounds having stabilized regions |
| SG194034A1 (en) | 2011-04-01 | 2013-11-29 | Mannkind Corp | Blister package for pharmaceutical cartridges |
| WO2012174472A1 (en) | 2011-06-17 | 2012-12-20 | Mannkind Corporation | High capacity diketopiperazine microparticles |
| MX2014004983A (es) | 2011-10-24 | 2014-09-22 | Mannkid Corp | Metodos y composiciones para tratar dolor. |
| ES2810153T3 (es) * | 2012-03-01 | 2021-03-08 | Novo Nordisk As | Profármacos de GLP-1 |
| KR102264177B1 (ko) | 2012-07-12 | 2021-06-11 | 맨카인드 코포레이션 | 건조 분말 약물 전달 시스템 및 방법 |
| WO2014066856A1 (en) | 2012-10-26 | 2014-05-01 | Mannkind Corporation | Inhalable influenza vaccine compositions and methods |
| EP3587404B1 (en) | 2013-03-15 | 2022-07-13 | MannKind Corporation | Microcrystalline diketopiperazine compositions, methods for preparation and use thereof |
| MX375448B (es) | 2013-07-18 | 2025-03-06 | Mannkind Corp | Composiciones farmacéuticas en polvo seco estables al calor y métodos. |
| EP3030294B1 (en) | 2013-08-05 | 2020-10-07 | MannKind Corporation | Insufflation apparatus |
| US10307464B2 (en) | 2014-03-28 | 2019-06-04 | Mannkind Corporation | Use of ultrarapid acting insulin |
| US10561806B2 (en) | 2014-10-02 | 2020-02-18 | Mannkind Corporation | Mouthpiece cover for an inhaler |
| RS63523B1 (sr) | 2018-04-05 | 2022-09-30 | Sun Pharmaceutical Ind Ltd | Novi glp-1 analozi |
| CN110070918B (zh) * | 2019-04-02 | 2022-12-27 | 重庆邮电大学 | 基于分子间相互作用的粗粒化方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE164852T1 (de) * | 1990-01-24 | 1998-04-15 | Douglas I Buckley | Glp-1-analoga verwendbar in der diabetesbehandlung |
| US5545618A (en) * | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
| SK155694A3 (en) * | 1992-06-15 | 1995-05-10 | Pfizer | Glucagon-like peptide, insulinotropin derivatives, method of their preparation, pharmaceutical agent containing and using these matters |
| EP0658568A1 (en) * | 1993-12-09 | 1995-06-21 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
| US5705483A (en) * | 1993-12-09 | 1998-01-06 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
| WO1998043658A1 (en) * | 1997-03-31 | 1998-10-08 | Eli Lilly And Company | Glucagon-like peptide-1 analogs |
-
1998
- 1998-04-10 FR FR9804559A patent/FR2777283B1/fr not_active Expired - Fee Related
-
1999
- 1999-02-25 NZ NZ334379A patent/NZ334379A/en unknown
- 1999-03-10 CA CA002263059A patent/CA2263059A1/fr not_active Abandoned
- 1999-03-11 NO NO19991199A patent/NO323137B1/no unknown
- 1999-03-12 ES ES99400613T patent/ES2212485T3/es not_active Expired - Lifetime
- 1999-03-12 ZA ZA9902035A patent/ZA992035B/xx unknown
- 1999-03-12 PL PL99331960A patent/PL331960A1/xx not_active IP Right Cessation
- 1999-03-12 DE DE69913242T patent/DE69913242T2/de not_active Expired - Fee Related
- 1999-03-12 AT AT99400613T patent/ATE255596T1/de not_active IP Right Cessation
- 1999-03-12 DK DK99400613T patent/DK0955314T3/da active
- 1999-03-12 EP EP99400613A patent/EP0955314B1/fr not_active Expired - Lifetime
- 1999-03-12 JP JP06691799A patent/JP3787242B2/ja not_active Expired - Fee Related
- 1999-03-12 HU HU9900604A patent/HUP9900604A3/hu unknown
- 1999-03-12 PT PT99400613T patent/PT955314E/pt unknown
- 1999-03-15 CN CNB991039874A patent/CN1305897C/zh not_active Expired - Fee Related
- 1999-03-15 BR BR9902014-9A patent/BR9902014A/pt not_active Application Discontinuation
- 1999-03-15 US US09/268,578 patent/US6620910B1/en not_active Expired - Fee Related
- 1999-04-09 AU AU23688/99A patent/AU761652B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JP3787242B2 (ja) | 2006-06-21 |
| CN1305897C (zh) | 2007-03-21 |
| CN1232038A (zh) | 1999-10-20 |
| PL331960A1 (en) | 1999-10-11 |
| PT955314E (pt) | 2004-03-31 |
| ES2212485T3 (es) | 2004-07-16 |
| ZA992035B (en) | 1999-09-27 |
| HUP9900604A2 (hu) | 1999-09-28 |
| DK0955314T3 (da) | 2004-04-13 |
| DE69913242T2 (de) | 2004-09-09 |
| US6620910B1 (en) | 2003-09-16 |
| ATE255596T1 (de) | 2003-12-15 |
| HU9900604D0 (en) | 1999-05-28 |
| CA2263059A1 (fr) | 1999-10-10 |
| JPH11310597A (ja) | 1999-11-09 |
| FR2777283B1 (fr) | 2000-11-24 |
| NO991199L (no) | 1999-10-11 |
| NZ334379A (en) | 1999-10-28 |
| EP0955314A2 (fr) | 1999-11-10 |
| EP0955314B1 (fr) | 2003-12-03 |
| BR9902014A (pt) | 2000-05-02 |
| NO991199D0 (no) | 1999-03-11 |
| AU761652B2 (en) | 2003-06-05 |
| AU2368899A (en) | 1999-10-21 |
| FR2777283A1 (fr) | 1999-10-15 |
| HK1022320A1 (en) | 2000-08-04 |
| DE69913242D1 (de) | 2004-01-15 |
| HUP9900604A3 (en) | 2001-01-29 |
| EP0955314A3 (fr) | 2000-03-29 |
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