NO330686B1 - Glukagonliknende peptid-1 forbindelser og anvendelse derav - Google Patents
Glukagonliknende peptid-1 forbindelser og anvendelse derav Download PDFInfo
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- NO330686B1 NO330686B1 NO20025949A NO20025949A NO330686B1 NO 330686 B1 NO330686 B1 NO 330686B1 NO 20025949 A NO20025949 A NO 20025949A NO 20025949 A NO20025949 A NO 20025949A NO 330686 B1 NO330686 B1 NO 330686B1
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- Norway
- Prior art keywords
- glp
- seq
- glu
- amino acid
- compounds
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Classifications
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- 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
- A61K38/26—Glucagons
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P3/04—Anorexiants; Antiobesity agents
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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
- 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
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- C07K14/605—Glucagons
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Biophysics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US21217100P | 2000-06-16 | 2000-06-16 | |
US24034900P | 2000-10-13 | 2000-10-13 | |
PCT/US2001/016474 WO2001098331A2 (fr) | 2000-06-16 | 2001-06-01 | Analogues de glp-1 (glucagone-like peptide 1) |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20025949D0 NO20025949D0 (no) | 2002-12-11 |
NO20025949L NO20025949L (no) | 2002-12-11 |
NO330686B1 true NO330686B1 (no) | 2011-06-06 |
Family
ID=26906843
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20025949A NO330686B1 (no) | 2000-06-16 | 2002-12-11 | Glukagonliknende peptid-1 forbindelser og anvendelse derav |
Country Status (33)
Country | Link |
---|---|
US (2) | US7084243B2 (fr) |
EP (2) | EP1695983B1 (fr) |
JP (1) | JP4716641B2 (fr) |
KR (1) | KR100847615B1 (fr) |
CN (1) | CN100469791C (fr) |
AR (1) | AR031701A1 (fr) |
AT (2) | ATE346093T1 (fr) |
AU (2) | AU6479101A (fr) |
BR (1) | BR0111562A (fr) |
CA (1) | CA2412004C (fr) |
CY (2) | CY1105917T1 (fr) |
CZ (1) | CZ304002B6 (fr) |
DE (2) | DE60137876D1 (fr) |
DK (2) | DK1695983T3 (fr) |
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Families Citing this family (158)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001000654A2 (fr) | 1999-06-29 | 2001-01-04 | Pharmaceutical Discovery Corporation | Purification et stabilisation de produits pharmaceutiques a base de peptides et de proteines |
US9006175B2 (en) | 1999-06-29 | 2015-04-14 | Mannkind Corporation | Potentiation of glucose elimination |
DK1695983T3 (da) * | 2000-06-16 | 2009-05-18 | Lilly Co Eli | Glucagon-lignende peptid-1 analoger |
DK1326630T3 (da) | 2000-09-18 | 2008-09-15 | Sanos Bioscience As | Anvendelse af GLP-2-peptider |
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 |
US20030119734A1 (en) * | 2001-06-28 | 2003-06-26 | Flink James M. | Stable formulation of modified GLP-1 |
CN1363654A (zh) | 2001-07-19 | 2002-08-14 | 上海华谊生物技术有限公司 | 生产促胰岛素分泌肽glp-1(7-36)的基因工程菌以及生产glp-1(7-36)的方法 |
HUP0501192A3 (en) | 2001-08-23 | 2006-06-28 | Lilly Co Eli | Glucagon-like peptide-1 analogs |
GB0121709D0 (en) * | 2001-09-07 | 2001-10-31 | Imp College Innovations Ltd | Food inhibition agent |
IL160917A0 (en) * | 2001-10-18 | 2004-08-31 | Bristol Myers Squibb Co | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
EP2261250B1 (fr) | 2001-12-21 | 2015-07-01 | Human Genome Sciences, Inc. | Protéines de fusion d'albumine et GCSF |
DE60217918T2 (de) * | 2001-12-29 | 2007-11-15 | Novo Nordisk A/S | Kombinierte verwendung einer glp-1-verbindung und eines aldose reduktase inhibitors |
NZ534125A (en) * | 2002-02-20 | 2006-11-30 | Emisphere Tech Inc | A formulation comprising a GLP-1 compound and a delivery agent |
EP1894591B1 (fr) | 2002-03-20 | 2013-06-26 | MannKind Corporation | Cartouche pour un appareil d'inhalation |
WO2003103572A2 (fr) * | 2002-06-04 | 2003-12-18 | Eli Lilly And Company | Analogues modifies du peptide-1 de type glucagon (glp-1) |
US20080260838A1 (en) * | 2003-08-01 | 2008-10-23 | Mannkind Corporation | Glucagon-like peptide 1 (glp-1) pharmaceutical formulations |
US7790681B2 (en) | 2002-12-17 | 2010-09-07 | Amylin Pharmaceuticals, Inc. | Treatment of cardiac arrhythmias with GLP-1 receptor ligands |
US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
WO2004067548A2 (fr) * | 2003-01-31 | 2004-08-12 | Theratechnologies Inc. | Metabolites chimiquement modifies de peptides regulateurs et methodes de production et d'utilisation associees |
CN1750842A (zh) * | 2003-02-19 | 2006-03-22 | 研究及应用科学协会股份有限公司 | Glp-1的类似物 |
ATE549028T1 (de) | 2003-05-15 | 2012-03-15 | Tufts College | Stabile analoga von glp-1 |
EP1631308B1 (fr) * | 2003-05-30 | 2013-07-31 | Amylin Pharmaceuticals, LLC | Nouveaux procedes et nouvelles compositions pour une administration amelioree par voie muqueuse de peptides et de proteines |
WO2004105790A1 (fr) * | 2003-06-03 | 2004-12-09 | Novo Nordisk A/S | Compositions peptidiques pharmaceutiques stabilisees |
CN102940879B (zh) * | 2003-06-03 | 2017-06-06 | 诺沃挪第克公司 | 稳定化的药物肽组合物 |
PT1641823E (pt) | 2003-06-12 | 2011-11-08 | Lilly Co Eli | Proteínas de fusão de análogos de glp-1 |
KR101243648B1 (ko) * | 2003-11-20 | 2013-03-14 | 노보 노르디스크 에이/에스 | 제조 및 주사 장치용에 최적인 프로필렌 글리콜 함유펩티드 제제 |
EP2298337B1 (fr) | 2003-12-09 | 2017-02-22 | Novo Nordisk A/S | Régulation des préférences alimentaires en utilisant des agonistes du GLP-1 |
ES2393335T3 (es) | 2003-12-16 | 2012-12-20 | Ipsen Pharma | Análogos de GLP-1 |
CA2550695A1 (fr) * | 2003-12-16 | 2005-06-30 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R | Compositions pharmaceutiques glp-1 |
BRPI0506694A (pt) | 2004-01-08 | 2007-05-02 | Theratechnologies Inc | análogos de peptìdeo-1 semelhante ao glucagon com longa duração de ação |
NZ550602A (en) | 2004-04-30 | 2009-11-27 | Dow Agrosciences Llc | Plants comprising herbicide resistance gene encoding aryloxyalkanoate dioxygenase |
US20090069226A1 (en) * | 2004-05-28 | 2009-03-12 | Amylin Pharmaceuticals, Inc. | Transmucosal delivery of peptides and proteins |
JP2008501765A (ja) | 2004-06-11 | 2008-01-24 | ノボ ノルディスク アクティーゼルスカブ | Glp−1アゴニストを用いた薬剤誘発性肥満の中和 |
DK1786784T3 (da) | 2004-08-20 | 2011-02-14 | Mannkind Corp | Katalyse af diketopiperazinsyntese |
CN104436170B (zh) | 2004-08-23 | 2018-02-23 | 曼金德公司 | 用于药物输送的二酮哌嗪盐 |
PL1789434T3 (pl) * | 2004-08-31 | 2014-07-31 | Novo Nordisk As | Zastosowanie tris(hydroksymetylo)aminometanu do stabilizacji peptydów, polipeptydów i białek |
EP1799711B1 (fr) | 2004-10-07 | 2012-06-20 | Novo Nordisk A/S | Composes d'exendin-4 a action prolongee |
WO2006037810A2 (fr) * | 2004-10-07 | 2006-04-13 | Novo Nordisk A/S | Composes de glp-1 a action prolongee |
JP5175103B2 (ja) | 2004-11-12 | 2013-04-03 | ノヴォ ノルディスク アー/エス | 安定なペプチド製剤 |
JP4785206B2 (ja) | 2005-01-14 | 2011-10-05 | ウクスィ・グランドチャンプ・ファーマシューティカル・テクノロジー・カンパニー・リミテッド | 修飾されたエキセンディン(Exendins)及びその使用 |
WO2006083761A2 (fr) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solutions de solvant/polymere utilisees comme vehicules de suspension |
US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
WO2006098524A1 (fr) * | 2005-03-18 | 2006-09-21 | Ajinomoto Co., Inc. | Agent prophylactique/therapeutique pour la maladie intestinale induite par le stress |
DE602006017202D1 (de) * | 2005-05-13 | 2010-11-11 | Lilly Co Eli | Pegylierte glp-1-verbindungen |
MX2008001468A (es) * | 2005-06-30 | 2008-04-07 | Sod Conseils Rech Applic | Composiciones farmaceuticas del peptido similar al glucagon-1. |
HUE028623T2 (en) | 2005-09-14 | 2016-12-28 | Mannkind Corp | Active substance formulation method based on increasing the affinity of the active ingredient for binding to the surface of crystalline microparticles |
EP1947926B1 (fr) | 2005-10-28 | 2014-11-26 | Dow AgroSciences LLC | Nouveaux gènes de résistance aux herbicides |
ES2572952T3 (es) | 2005-11-07 | 2016-06-03 | Indiana University Research And Technology Corporation | Análogos de glucagón que muestran solubilidad y estabilidad fisiológicas |
CN100374462C (zh) * | 2005-11-21 | 2008-03-12 | 大连帝恩生物工程有限公司 | 截短胰高血糖素样肽1(sGLP-1)、制法及其应用 |
US8841255B2 (en) | 2005-12-20 | 2014-09-23 | Duke University | Therapeutic agents comprising fusions of vasoactive intestinal peptide and elastic peptides |
EP1971355B1 (fr) | 2005-12-20 | 2020-03-11 | Duke University | Procedes et compositions pour l'administration d'agents actifs a proprietes pharmacologiques ameliorees |
US20130172274A1 (en) | 2005-12-20 | 2013-07-04 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
WO2008063203A2 (fr) * | 2006-01-27 | 2008-05-29 | Whitehead Institute For Biomedical Research | Compositions et méthodes de silençage efficace de gènes dans des végétaux |
IN2015DN00888A (fr) | 2006-02-22 | 2015-07-10 | Mannkind Corp | |
MX2008013304A (es) | 2006-04-20 | 2008-10-27 | Amgen Inc | Compuestos de peptido 1 tipo glucagon. |
CA2651855C (fr) | 2006-05-30 | 2011-08-02 | Intarcia Therapeutics, Inc. | Modulateur de flux pour un systeme d'administration osmotique presentant deux pieces et conduite interne |
CN101466398A (zh) * | 2006-06-09 | 2009-06-24 | 诺瓦提斯公司 | 稳定的胰岛素样生长因子多肽 |
CA2655923A1 (fr) * | 2006-07-06 | 2008-01-10 | Amylin Pharmaceuticals, Inc. | Peptides semblables au glucagon et leurs utilisations |
US8071103B2 (en) * | 2006-07-18 | 2011-12-06 | Centocor, Inc. | Pharmaceutical composition comprising a human GLP-1 mimetibody |
ES2422864T3 (es) | 2006-08-09 | 2013-09-16 | Intarcia Therapeutics, Inc | Sistemas de liberación osmótica y unidades de pistón |
KR100851560B1 (ko) * | 2006-12-27 | 2008-08-11 | 고려대학교 산학협력단 | 새로운 글루카곤 유사 펩타이드-1 (glp-1) 작용제 및 그용도 |
ES2628063T3 (es) | 2007-01-05 | 2017-08-01 | Indiana University Research And Technology Corporation | Análogos de glucagón que muestran una mayor solubilidad en tampones de pH fisiológicos |
CN101041693B (zh) * | 2007-02-06 | 2011-08-17 | 珠海联邦制药股份有限公司 | 一种降血糖多肽及其应用 |
CA2677932A1 (fr) | 2007-02-15 | 2008-08-21 | Indiana University Research And Technology Corporation | Co-agonistes des recepteurs du glucagon/glp-1 |
PT2157967E (pt) | 2007-04-23 | 2013-04-03 | Intarcia Therapeutics Inc | Formulações de suspensões de péptidos insulinotrópicos e suas utilizações |
GB2448895A (en) * | 2007-05-01 | 2008-11-05 | Activotec Spp Ltd | GLP-1 like compounds and uses thereof |
US8464239B2 (en) * | 2007-06-11 | 2013-06-11 | Red Hat, Inc. | Real-time installation and/or configuration assistant |
EP3260129A1 (fr) * | 2007-08-03 | 2017-12-27 | Eli Lilly and Company | Un composé du fgf-21 et d'un composé du glp-1 pour son utilisation dans le traitement des diabètes |
WO2009055740A2 (fr) * | 2007-10-24 | 2009-04-30 | Mannkind Corporation | Procédé de prévention des effets indésirables produits par glp-1 |
US8785396B2 (en) | 2007-10-24 | 2014-07-22 | Mannkind Corporation | Method and composition for treating migraines |
BRPI0818874A2 (pt) * | 2007-10-24 | 2015-05-05 | Mannkind Corp | Liberação de agentes ativos |
JP5771005B2 (ja) | 2007-10-30 | 2015-08-26 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation | グルカゴンアンタゴニスト及びglp−1アゴニスト活性を示す化合物 |
ES2509883T3 (es) | 2007-10-30 | 2014-10-20 | Indiana University Research And Technology Corporation | Antagonistas de glucagón |
EP2240155B1 (fr) | 2008-02-13 | 2012-06-06 | Intarcia Therapeutics, Inc | Dispositifs, formulations et méthodes d administration de plusieurs agents bénéfiques |
ES2570400T3 (es) | 2008-06-13 | 2016-05-18 | Mannkind Corp | Un inhalador de polvo seco y un sistema para el suministro de fármacos |
US8485180B2 (en) | 2008-06-13 | 2013-07-16 | Mannkind Corporation | Dry powder drug delivery system |
CL2009001424A1 (es) | 2008-06-17 | 2010-04-30 | Univ Indiana Res & Tech Corp | Peptido tipo glucagon; dimero que comprende dos de dichos peptidos; composicion farmaceutica que lo comprende; y su uso para tratar diabetes o inducir perdida de peso. |
CL2009001425A1 (es) | 2008-06-17 | 2010-04-30 | Univ Indiana Res & Tech Corp | Analogos de glucagon con un aminoacido aromatico grande que carece de cadena lateral de imidazol que le confiere actividad agonista del receptor gip; composiciones farmaceutica; kit que los contiene y uso para reducir el aumento de peso, tratar la diabetes o inducir paralisis del tracto intestinal. |
CA2727161A1 (fr) * | 2008-06-17 | 2009-12-23 | Indiana University Research And Technology Corporation | Analogues de glucagon presentant des tampons de ph physiologique presentant une solubilite et une stabilite ameliorees |
JP5479465B2 (ja) | 2008-06-20 | 2014-04-23 | マンカインド コーポレイション | 吸入努力をリアルタイムにプロファイルする対話式機器および方法 |
WO2009158704A2 (fr) * | 2008-06-27 | 2009-12-30 | Duke University | Agents thérapeutiques comprenant des peptides de type élastine |
TWI532497B (zh) | 2008-08-11 | 2016-05-11 | 曼凱公司 | 超快起作用胰島素之用途 |
CN101337989B (zh) * | 2008-08-28 | 2012-10-24 | 中国药科大学 | 一类新型胰高血糖素样肽-1(glp-1)类似物及其应用 |
CN101367873B (zh) * | 2008-10-08 | 2011-05-04 | 南开大学 | 一种改构的胰高血糖素样肽-1的类似物和修饰物及其应用 |
EP2344519B1 (fr) | 2008-11-07 | 2016-09-28 | The General Hospital Corporation | Fragments c-terminaux du peptide 1 de type glucagon (glp-1) |
AU2009327418A1 (en) | 2008-12-19 | 2010-06-24 | Indiana University Research And Technology Corporation | Amide based glucagon superfamily peptide prodrugs |
US8314106B2 (en) | 2008-12-29 | 2012-11-20 | Mannkind Corporation | Substituted diketopiperazine analogs for use as drug delivery agents |
EP2405963B1 (fr) | 2009-03-11 | 2013-11-06 | MannKind Corporation | Appareil, système et procédé de mesure de résistance d'un inhalateur |
KR101875969B1 (ko) | 2009-06-12 | 2018-07-06 | 맨카인드 코포레이션 | 한정된 비표면적을 갖는 디케토피페라진 마이크로입자 |
IN2012DN00377A (fr) | 2009-06-16 | 2015-08-21 | Univ Indiana Res & Tech Corp | |
ES2537287T3 (es) | 2009-07-13 | 2015-06-05 | Zealand Pharma A/S | Análogos de glucagón acilados |
AU2010282250B2 (en) * | 2009-08-14 | 2015-11-12 | Immunoforge Co., Ltd. | Modified Vasoactive Intestinal Peptides |
KR101823699B1 (ko) | 2009-09-28 | 2018-01-30 | 인타르시아 세라퓨틱스 인코포레이티드 | 실질 항정상태 약물 전달의 신속 확립 및/또는 종결 |
US20120264684A1 (en) * | 2009-10-30 | 2012-10-18 | Yasuhiro Kajihara | Glycosylated Form of Antigenic GLP-1 Analogue |
JP5784622B2 (ja) | 2009-11-03 | 2015-09-24 | マンカインド コーポレ−ション | 吸入活動をシミュレートするための装置及び方法 |
EP2504019A2 (fr) | 2009-11-25 | 2012-10-03 | ArisGen SA | Composition à libération par voie muqueuse contenant un peptide, un agent de couronne et/ou un contre-ion |
US8703701B2 (en) | 2009-12-18 | 2014-04-22 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
US8551946B2 (en) | 2010-01-27 | 2013-10-08 | Indiana University Research And Technology Corporation | Glucagon antagonist-GIP agonist conjugates and compositions for the treatment of metabolic disorders and obesity |
WO2011123943A1 (fr) | 2010-04-09 | 2011-10-13 | Mount Sinai Hospital | Méthodes de traitement de troubles du tractus gastro-intestinal au moyen d'un agoniste glp-1 |
US9127088B2 (en) | 2010-05-13 | 2015-09-08 | Indiana University Research And Technology Corporation | Glucagon superfamily peptides exhibiting nuclear hormone receptor activity |
MX2012013005A (es) | 2010-05-13 | 2013-02-26 | Univ Indiana Res & Tech Corp | Peptidos de la superfamilia de glucagon que presentan actividad del receptor acoplado a proteinas g. |
ES2528496T3 (es) * | 2010-05-17 | 2015-02-10 | Betta Pharmaceuticals Co., Ltd. | Nuevos análogos de péptido similar a glucagón, composición, y métodos de uso |
MX359281B (es) | 2010-06-21 | 2018-09-21 | Mannkind Corp | Sistema y metodos para suministrar un farmaco en polvo seco. |
CA2796894A1 (fr) | 2010-06-24 | 2011-12-29 | Indiana University Research And Technology Corporation | Promedicaments peptidiques a base d'amides de la superfamille du glucagon |
RU2013103763A (ru) | 2010-07-02 | 2014-08-10 | Ангиохем Инк. | Короткие и содержащие d-аминокислоты полипептиды для терапевтических конъюгатов и их применения |
WO2012061466A2 (fr) | 2010-11-02 | 2012-05-10 | The General Hospital Corporation | Méthodes de traitement d'une maladie de stéatose |
BR112013015389A2 (pt) | 2010-12-22 | 2016-11-22 | Univ Indiana Res & Tech Corp | análogo de glucagon exibindo atividade de receptor gip |
US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
MX353285B (es) | 2011-04-01 | 2018-01-05 | Mannkind Corp | Paquete de blister para cartuchos farmaceuticos. |
CN102180963B (zh) * | 2011-04-22 | 2014-06-25 | 中国药科大学 | 胰高血糖素样肽-1(glp-1)类似物及其应用 |
CN102219850A (zh) * | 2011-05-03 | 2011-10-19 | 上海格尼生物技术有限公司 | 新的长效glp-1化合物 |
CA2873553C (fr) | 2011-06-06 | 2020-01-28 | Phasebio Pharmaceuticals, Inc. | Utilisation de peptides intestinaux vasoactifs (piv) modifies pour traiter l'hypertension |
WO2012174472A1 (fr) | 2011-06-17 | 2012-12-20 | Mannkind Corporation | Microparticules de dicétopipérazine de capacité élevée |
MX347703B (es) | 2011-06-22 | 2017-05-09 | Univ Indiana Res & Tech Corp | Co-agonistas del receptor de glucagon/glp-1. |
MX2013015168A (es) | 2011-06-22 | 2014-03-31 | Univ Indiana Res & Tech Corp | Co-agonista del receptor de glucagon/glp-1. |
WO2013006692A2 (fr) | 2011-07-06 | 2013-01-10 | The General Hospital Corporation | Méthodes de traitement utilisant un pentapeptide dérivé de l'extrémité c-terminale du glp-1 (glucagon-like peptide 1) |
CA2849673A1 (fr) * | 2011-09-23 | 2013-03-28 | Novo Nordisk A/S | Nouveaux analogues du glucagon |
CN103945859A (zh) | 2011-10-24 | 2014-07-23 | 曼金德公司 | 用于治疗疼痛的方法和组合物 |
CA2847246A1 (fr) | 2011-11-17 | 2013-05-23 | Indiana University Research And Technology Corporation | Peptides de la superfamille du glucagon presentant une action sur les recepteurs aux glucocorticoides |
KR20150023013A (ko) | 2012-06-21 | 2015-03-04 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 수용체 활성을 나타내는 글루카곤 유사체 |
WO2014012069A2 (fr) | 2012-07-12 | 2014-01-16 | Mannkind Corporation | Systèmes et procédés de libération de médicament en poudre sèche |
EP2911690A1 (fr) | 2012-10-26 | 2015-09-02 | MannKind Corporation | Compositions et procédés de vaccin antigrippal inhalable |
CN103087178A (zh) * | 2012-11-30 | 2013-05-08 | 中国药科大学 | 长效化胰高血糖素样肽-1(glp-1)类似物及其应用 |
CN103087175A (zh) * | 2012-11-30 | 2013-05-08 | 中国药科大学 | 新型长效化胰高血糖素样肽-1(glp-1)类似物及其应用 |
CN103087176A (zh) * | 2012-11-30 | 2013-05-08 | 中国药科大学 | 长效化胰高血糖素样肽-1(glp-1)类似物及其应用 |
CN103087179A (zh) * | 2012-11-30 | 2013-05-08 | 中国药科大学 | 长效化胰高血糖素样肽-1(glp-1)类似物及其应用 |
CN103087177A (zh) * | 2012-11-30 | 2013-05-08 | 中国药科大学 | 一类长效化胰高血糖素样肽-1(glp-1)类似物及其应用 |
AU2014228415B2 (en) | 2013-03-15 | 2018-08-09 | Mannkind Corporation | Microcrystalline diketopiperazine compositions and methods |
MX362275B (es) | 2013-04-18 | 2019-01-10 | Novo Nordisk As | Co-agonista de peptido similar a glucagon tipo 1 (glp-1) receptor de glucagon de larga duracion, estables para uso medico. |
KR102321339B1 (ko) | 2013-07-18 | 2021-11-02 | 맨카인드 코포레이션 | 열-안정성 건조 분말 약제학적 조성물 및 방법 |
US11446127B2 (en) | 2013-08-05 | 2022-09-20 | Mannkind Corporation | Insufflation apparatus and methods |
CN104262481B (zh) * | 2013-08-09 | 2018-02-09 | 天津药物研究院有限公司 | 一种侧链修饰的长效glp‑1类似物的制备方法及其应用 |
CN103405753B (zh) * | 2013-08-13 | 2016-05-11 | 上海仁会生物制药股份有限公司 | 稳定的促胰岛素分泌肽水针药物组合物 |
US10307464B2 (en) | 2014-03-28 | 2019-06-04 | Mannkind Corporation | Use of ultrarapid acting insulin |
US11052132B2 (en) | 2014-05-08 | 2021-07-06 | Phasebio Pharmaceuticals, Inc. | Methods and compositions for treating cystic fibrosis |
WO2015185640A1 (fr) | 2014-06-04 | 2015-12-10 | Novo Nordisk A/S | Co-agonistes de récepteur du glucagon/glp-1 à usage médical |
US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
US10561806B2 (en) | 2014-10-02 | 2020-02-18 | Mannkind Corporation | Mouthpiece cover for an inhaler |
EP3209682B1 (fr) * | 2014-10-24 | 2020-12-30 | Merck Sharp & Dohme Corp. | Co-agonistes des récepteurs du glucagon et du glp-1 |
EP3256151B1 (fr) | 2015-02-09 | 2020-08-05 | Phasebio Pharmaceuticals, Inc. | Méthodes et compositions pour traiter des maladies et des troubles musculaires |
US10925639B2 (en) | 2015-06-03 | 2021-02-23 | Intarcia Therapeutics, Inc. | Implant placement and removal systems |
KR20170080521A (ko) * | 2015-12-31 | 2017-07-10 | 한미약품 주식회사 | 글루카곤, glp-1 및 gip 수용체 모두에 활성을 갖는 삼중 활성체 |
KR102574993B1 (ko) | 2016-05-16 | 2023-09-06 | 인타르시아 세라퓨틱스 인코포레이티드 | 글루카곤-수용체 선택적 폴리펩티드 및 이들의 이용 방법 |
USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
KR20190104039A (ko) | 2017-01-03 | 2019-09-05 | 인타르시아 세라퓨틱스 인코포레이티드 | Glp-1 수용체 효능제의 연속적인 투여 및 약물의 동시-투여를 포함하는 방법 |
AR112480A1 (es) | 2017-08-24 | 2019-10-30 | Novo Nordisk As | Composiciones de glp-1 y sus usos |
WO2019140021A1 (fr) | 2018-01-12 | 2019-07-18 | Eli Lilly And Company | Polythérapie |
KR20200141469A (ko) | 2018-04-05 | 2020-12-18 | 썬 파마슈티칼 인더스트리스 리미티드 | 신규한 glp-1 유사체 |
TWI705820B (zh) | 2018-06-22 | 2020-10-01 | 美商美國禮來大藥廠 | Gip/glp1促效劑組合物 |
CA3116023A1 (fr) | 2018-10-11 | 2020-04-16 | Intarcia Therapeutics, Inc. | Polypeptides analogues d'amyline humaine et procedes d'utilisation |
KR20210081376A (ko) | 2018-10-30 | 2021-07-01 | 지아닝 리우 | Glp-1 수용체 작용제 활성을 갖는 glp-1 폴리펩티드 및 그의 용도 |
CA3056663C (fr) | 2019-04-05 | 2022-10-18 | Jeffrey S. RIESMEYER | Utilisation du dulaglutide pour reduire le risque d'evenement cardiovasculaire chez les patients atteints du diabete de type 2 |
CN112898406B (zh) * | 2019-10-12 | 2023-11-10 | 深圳纳福生物医药有限公司 | 不同构型的glp-1类似肽修饰二聚体及其制备方法在治疗ii型糖尿病中的应用 |
WO2021139744A1 (fr) | 2020-01-11 | 2021-07-15 | Beijing Ql Biopharmaceutical Co., Ltd. | Conjugués de protéines de fusion du glp-1 et du fgf21 |
AU2021208601A1 (en) | 2020-02-18 | 2022-07-28 | Novo Nordisk A/S | Glp-1 compositions and uses thereof |
US11981718B2 (en) * | 2020-05-27 | 2024-05-14 | Ampsource Biopharma Shanghai Inc. | Dual-function protein for lipid and blood glucose regulation |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5545618A (en) | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
ATE164852T1 (de) * | 1990-01-24 | 1998-04-15 | Douglas I Buckley | Glp-1-analoga verwendbar in der diabetesbehandlung |
US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
US5705483A (en) * | 1993-12-09 | 1998-01-06 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
UA65549C2 (uk) * | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
DK1019077T4 (da) | 1997-08-08 | 2011-03-07 | Amylin Pharmaceuticals Inc | Hidtil ukendte exendinagonistforbindelser |
DK1032587T4 (da) | 1997-11-14 | 2013-04-08 | Amylin Pharmaceuticals Llc | Hidtil ukendte exendinagonist-forbindelser |
ATE381939T1 (de) | 1997-11-14 | 2008-01-15 | Amylin Pharmaceuticals Inc | Neuartige exendin agonisten |
US6380357B2 (en) * | 1997-12-16 | 2002-04-30 | Eli Lilly And Company | Glucagon-like peptide-1 crystals |
AU2610799A (en) | 1998-02-27 | 1999-09-15 | Novo Nordisk A/S | Glp-1 derivatives with helix-content exceeding 25 per cent, forming partially structured micellar-like aggregates |
JP2002512175A (ja) | 1998-02-27 | 2002-04-23 | ノボ ノルディスク アクティーゼルスカブ | Glp−1類似体の誘導体類 |
EP1306091A3 (fr) * | 1998-07-31 | 2003-05-21 | Novo Nordisk A/S | Stimulation de la prolifération des cellules de beta |
US6429197B1 (en) * | 1998-10-08 | 2002-08-06 | Bionebraska, Inc. | Metabolic intervention with GLP-1 or its biologically active analogues to improve the function of the ischemic and reperfused brain |
DK1695983T3 (da) * | 2000-06-16 | 2009-05-18 | Lilly Co Eli | Glucagon-lignende peptid-1 analoger |
CZ306180B6 (cs) * | 2000-12-07 | 2016-09-14 | Eli Lilly And Company | GLP-1 fúzní proteiny |
DE60228972D1 (de) * | 2001-07-31 | 2008-10-30 | Us Gov Health & Human Serv | Glp 1 exendin 4 peptidanaloga und deren verwendungen |
AU2010279305A1 (en) * | 2009-08-07 | 2012-03-01 | Perry Felix | Method and apparatus for surface and subsurface sanitizing of food products in a cooking appliance using ultraviolet light |
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