ES2547529T3 - Formulación en polvo seco inhalable que comprende GLP-1 para usar en el tratamiento de la hiperglucemia y diabetes por administración pulmonar - Google Patents
Formulación en polvo seco inhalable que comprende GLP-1 para usar en el tratamiento de la hiperglucemia y diabetes por administración pulmonar Download PDFInfo
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- ES2547529T3 ES2547529T3 ES08841194.7T ES08841194T ES2547529T3 ES 2547529 T3 ES2547529 T3 ES 2547529T3 ES 08841194 T ES08841194 T ES 08841194T ES 2547529 T3 ES2547529 T3 ES 2547529T3
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- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Pulmonology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (9)
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| US98236807P | 2007-10-24 | 2007-10-24 | |
| US982368P | 2007-10-24 | ||
| US98562007P | 2007-11-05 | 2007-11-05 | |
| US985620P | 2007-11-05 | ||
| US3374008P | 2008-03-04 | 2008-03-04 | |
| US33740P | 2008-03-04 | ||
| US5212708P | 2008-05-09 | 2008-05-09 | |
| US52127P | 2008-05-09 | ||
| PCT/US2008/081218 WO2009055740A2 (en) | 2007-10-24 | 2008-10-24 | Method of preventing adverse effects by glp-1 |
Publications (1)
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| ES2547529T3 true ES2547529T3 (es) | 2015-10-07 |
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| ES08841194.7T Active ES2547529T3 (es) | 2007-10-24 | 2008-10-24 | Formulación en polvo seco inhalable que comprende GLP-1 para usar en el tratamiento de la hiperglucemia y diabetes por administración pulmonar |
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| JP (2) | JP2011500850A (https=) |
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| PL (1) | PL2211842T3 (https=) |
| RU (2) | RU2474415C2 (https=) |
| WO (1) | WO2009055740A2 (https=) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1808438T3 (da) | 1999-06-29 | 2014-10-27 | Mannkind Corp | Rensning og stabilisering af peptid og proteiner i lægemidler |
| US9006175B2 (en) | 1999-06-29 | 2015-04-14 | Mannkind Corporation | Potentiation of glucose elimination |
| WO2003080149A2 (en) | 2002-03-20 | 2003-10-02 | Mannkind Corporation | Inhalation apparatus |
| US20080260838A1 (en) * | 2003-08-01 | 2008-10-23 | Mannkind Corporation | Glucagon-like peptide 1 (glp-1) pharmaceutical formulations |
| US9078866B2 (en) * | 2003-08-01 | 2015-07-14 | Mannkind Corporation | Method for treating hyperglycemia with GLP-1 |
| US8921311B2 (en) | 2003-08-01 | 2014-12-30 | Mannkind Corporation | Method for treating hyperglycemia |
| PL1786784T3 (pl) | 2004-08-20 | 2011-04-29 | Mannkind Corp | Kataliza syntezy diketopiperazyn |
| KR101644250B1 (ko) | 2004-08-23 | 2016-07-29 | 맨카인드 코포레이션 | 약물 전달용 디케토피페라진염, 디케토모르포린염 또는 디케토디옥산염 |
| CN104324362B (zh) | 2005-09-14 | 2018-04-24 | 曼金德公司 | 以提高活性试剂对结晶微粒表面的亲和力为基础的药物配制方法 |
| IN2015DN00888A (https=) | 2006-02-22 | 2015-07-10 | Mannkind Corp | |
| JP2011500850A (ja) | 2007-10-24 | 2011-01-06 | マンカインド コーポレイション | Ｇｌｐ−１による副作用を防止する方法 |
| US8785396B2 (en) * | 2007-10-24 | 2014-07-22 | Mannkind Corporation | Method and composition for treating migraines |
| WO2009121020A1 (en) * | 2008-03-27 | 2009-10-01 | Mannkind Corporation | A dry powder inhalation system |
| ES2929343T3 (es) | 2008-06-13 | 2022-11-28 | Mannkind Corp | Inhalador de polvo seco accionado por aspiración para la administración de fármacos |
| US8485180B2 (en) | 2008-06-13 | 2013-07-16 | Mannkind Corporation | Dry powder drug delivery system |
| KR101628410B1 (ko) | 2008-06-20 | 2016-06-08 | 맨카인드 코포레이션 | 흡입 활동에 관한 실시간 프로파일링을 위한 대화형 장치 및 방법 |
| TWI614024B (zh) | 2008-08-11 | 2018-02-11 | 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 |
| MX2011009251A (es) * | 2009-03-04 | 2011-11-18 | Mannkind Corp | Sistema mejorado de suministro de farmaco en polvo seco. |
| DK2405963T3 (da) | 2009-03-11 | 2013-12-16 | Mannkind Corp | Apparat, system og fremgangsmåde til at måle modstand i en inhalator |
| CN104721825B (zh) * | 2009-06-12 | 2019-04-12 | 曼金德公司 | 具有确定比表面积的二酮哌嗪颗粒 |
| EP3556356B1 (en) * | 2009-06-12 | 2021-05-05 | MannKind Corporation | Diketopiperazine microparticles with defined isomer content |
| US8642548B2 (en) | 2009-08-07 | 2014-02-04 | Mannkind Corporation | Val (8) GLP-1 composition and method for treating functional dyspepsia and/or irritable bowel syndrome |
| MX2012005091A (es) * | 2009-11-02 | 2012-06-19 | Mannkind Corp | Reactor para producir particulas farmaceuticas en un procedimiento de precipitacion. |
| EP2496253B1 (en) * | 2009-11-02 | 2019-01-09 | MannKind Corporation | Apparatus and method for cryogranulating a pharmaceutical composition |
| AU2015203301B2 (en) * | 2009-11-02 | 2017-05-25 | Mannkind Corporation | Reactor for producing pharmaceutical particles in a precipitation process |
| WO2011056889A1 (en) | 2009-11-03 | 2011-05-12 | Mannkind Corporation | An apparatus and method for simulating inhalation efforts |
| IL223742A (en) | 2010-06-21 | 2016-06-30 | Mannkind Corp | A dry powder inhaler and preparation for it |
| MX340112B (es) * | 2010-11-09 | 2016-06-27 | Mannkind Corp | Composicion que comprende un agonista de receptor de serotonina y una dicetopiperazina para el tratamiento de migrañas. |
| AU2012236150B2 (en) | 2011-04-01 | 2016-03-31 | Mannkind Corporation | Blister package for pharmaceutical cartridges |
| WO2012174472A1 (en) | 2011-06-17 | 2012-12-20 | Mannkind Corporation | High capacity diketopiperazine microparticles |
| BR112014009686A2 (pt) | 2011-10-24 | 2018-08-07 | Mannkind Corp | composição analgésica inalável, pó seco e método para tratar dor |
| CN104619369B (zh) | 2012-07-12 | 2018-01-30 | 曼金德公司 | 干粉药物输送系统和方法 |
| AU2013308693A1 (en) * | 2012-08-29 | 2015-03-12 | Mannkind Corporation | Method and composition for treating hyperglycemia |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| US10159644B2 (en) | 2012-10-26 | 2018-12-25 | Mannkind Corporation | Inhalable vaccine compositions and methods |
| AU2013366692B2 (en) | 2012-12-21 | 2017-11-23 | Sanofi | Dual GLP1/GIP or trigonal GLP1/GIP/Glucagon agonists |
| AU2014228415B2 (en) | 2013-03-15 | 2018-08-09 | Mannkind Corporation | Microcrystalline diketopiperazine compositions and methods |
| MX375448B (es) | 2013-07-18 | 2025-03-06 | Mannkind Corp | Composiciones farmacéuticas en polvo seco estables al calor y métodos. |
| US11446127B2 (en) | 2013-08-05 | 2022-09-20 | Mannkind Corporation | Insufflation apparatus and methods |
| EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | Sanofi | Dual glp-1/gip receptor agonists |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| EP3080152A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Non-acylated exendin-4 peptide analogues |
| US10307464B2 (en) | 2014-03-28 | 2019-06-04 | Mannkind Corporation | Use of ultrarapid acting insulin |
| TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑 |
| TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物 |
| TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| US10561806B2 (en) | 2014-10-02 | 2020-02-18 | Mannkind Corporation | Mouthpiece cover for an inhaler |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| TW201706291A (zh) | 2015-07-10 | 2017-02-16 | 賽諾菲公司 | 作為選擇性肽雙重ｇｌｐ－１／升糖素受體促效劑之新毒蜥外泌肽（ｅｘｅｎｄｉｎ－４）衍生物 |
| KR102891823B1 (ko) | 2023-06-30 | 2025-12-01 | 주식회사 휴온스랩 | GLP (Glucagon Like Peptide) 유사체를 유효성분으로 포함하는 비만 예방 또는 치료용 약학적 조성물 |
| WO2025220834A1 (ko) * | 2024-04-16 | 2025-10-23 | 한미약품 주식회사 | 흡입제 조성물 |
Family Cites Families (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5120712A (en) * | 1986-05-05 | 1992-06-09 | The General Hospital Corporation | Insulinotropic hormone |
| US5614492A (en) * | 1986-05-05 | 1997-03-25 | The General Hospital Corporation | Insulinotropic hormone GLP-1 (7-36) and uses thereof |
| US6849708B1 (en) * | 1986-05-05 | 2005-02-01 | The General Hospital Corporation | Insulinotropic hormone and uses thereof |
| US5118666A (en) | 1986-05-05 | 1992-06-02 | The General Hospital Corporation | Insulinotropic hormone |
| US6645504B1 (en) * | 1987-06-24 | 2003-11-11 | Autoimmune Inc. | Bystander suppression of type I diabetes by oral administration of glucagon |
| US5545618A (en) * | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
| US6331318B1 (en) | 1994-09-30 | 2001-12-18 | Emisphere Technologies Inc. | Carbon-substituted diketopiperazine delivery systems |
| US5693338A (en) | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
| US5352461A (en) | 1992-03-11 | 1994-10-04 | Pharmaceutical Discovery Corporation | Self assembling diketopiperazine drug delivery system |
| DK36392D0 (da) * | 1992-03-19 | 1992-03-19 | Novo Nordisk As | Anvendelse af kemisk forbindelse |
| US6024090A (en) * | 1993-01-29 | 2000-02-15 | Aradigm Corporation | Method of treating a diabetic patient by aerosolized administration of insulin lispro |
| US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| TW402506B (en) | 1993-06-24 | 2000-08-21 | Astra Ab | Therapeutic preparation for inhalation |
| US6632456B1 (en) * | 1993-06-24 | 2003-10-14 | Astrazeneca Ab | Compositions for inhalation |
| US5705483A (en) * | 1993-12-09 | 1998-01-06 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
| US5574008A (en) * | 1994-08-30 | 1996-11-12 | Eli Lilly And Company | Biologically active fragments of glucagon-like insulinotropic peptide |
| US5877174A (en) | 1994-12-01 | 1999-03-02 | Toyama Chemical Co., Ltd. | 2,3-diketopiperazine derivatives or their salts |
| US5990077A (en) * | 1995-04-14 | 1999-11-23 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
| US6428771B1 (en) * | 1995-05-15 | 2002-08-06 | Pharmaceutical Discovery Corporation | Method for drug delivery to the pulmonary system |
| JP3098401B2 (ja) | 1995-07-12 | 2000-10-16 | 株式会社エルティーティー研究所 | 経鼻投与用製剤 |
| US6852690B1 (en) * | 1995-08-22 | 2005-02-08 | Amylin Pharmaceuticals, Inc. | Method and composition for enhanced parenteral nutrition |
| US5766620A (en) * | 1995-10-23 | 1998-06-16 | Theratech, Inc. | Buccal delivery of glucagon-like insulinotropic peptides |
| JP3634380B2 (ja) * | 1996-02-27 | 2005-03-30 | 帝人株式会社 | 粉末状経鼻投与組成物 |
| JPH1053765A (ja) * | 1996-06-04 | 1998-02-24 | Denso Corp | スメクチック液晶組成物及び液晶セル |
| US6006753A (en) * | 1996-08-30 | 1999-12-28 | Eli Lilly And Company | Use of GLP-1 or analogs to abolish catabolic changes after surgery |
| US6277819B1 (en) * | 1996-08-30 | 2001-08-21 | Eli Lilly And Company | Use of GLP-1 or analogs in treatment of myocardial infarction |
| JP3020141B2 (ja) * | 1996-10-07 | 2000-03-15 | 株式会社富士薬品 | 経鼻投与用製剤 |
| 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 |
| DE69732572T2 (de) * | 1996-11-12 | 2005-12-29 | Novo Nordisk A/S | Verwendung von glp-1 peptiden |
| US5981488A (en) * | 1997-03-31 | 1999-11-09 | Eli Lillly And Company | Glucagon-like peptide-1 analogs |
| EP1049486A4 (en) * | 1997-12-05 | 2006-01-04 | Lilly Co Eli | GLP-1 FORMULATIONS |
| US6380357B2 (en) * | 1997-12-16 | 2002-04-30 | Eli Lilly And Company | Glucagon-like peptide-1 crystals |
| US6998387B1 (en) * | 1998-03-19 | 2006-02-14 | Amylin Pharmaceuticals, Inc. | Human appetite control by glucagon-like peptide receptor binding compounds |
| FR2777283B1 (fr) * | 1998-04-10 | 2000-11-24 | Adir | Nouveaux composes peptidiques analogues du glucagon-peptide- 1 (7-37), leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| SE9802080D0 (sv) * | 1998-06-11 | 1998-06-11 | Hellstroem | Pharmaceutical composition for the treatment of functional dyspepsia and/or irritable bowel syndrome and new use of substances therein |
| US6087334A (en) * | 1998-08-21 | 2000-07-11 | Amylin Pharmaceuticals, Inc. | Anti-diabetic peptides |
| US6428805B1 (en) * | 1998-08-26 | 2002-08-06 | Teijin Limited | Powdery nasal compositions |
| BR9913284A (pt) * | 1998-08-28 | 2001-05-15 | Lilly Co Eli | Métodos para administrar peptìdeos insulinotrópicos |
| US6720407B1 (en) * | 1998-08-28 | 2004-04-13 | Eli Lilly And Company | Method for administering insulinotropic peptides |
| US6375975B1 (en) * | 1998-12-21 | 2002-04-23 | Generex Pharmaceuticals Incorporated | Pharmaceutical compositions for buccal and pulmonary application |
| DE60026982T2 (de) | 1999-04-05 | 2006-11-16 | Mannkind Corp., Danbury | Verfahren zur bildung von feinem pulver |
| US6514500B1 (en) * | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
| EP1849475A1 (en) * | 1999-06-21 | 2007-10-31 | Eli Lilly & Company | Synergistic use of thiazolidinediones with glucagon-like peptide-1 and agonists thereof to treat non-insulin dependent diabetes |
| DK1808438T3 (da) | 1999-06-29 | 2014-10-27 | Mannkind Corp | Rensning og stabilisering af peptid og proteiner i lægemidler |
| US9006175B2 (en) * | 1999-06-29 | 2015-04-14 | Mannkind Corporation | Potentiation of glucose elimination |
| US7464706B2 (en) | 1999-07-23 | 2008-12-16 | Mannkind Corporation | Unit dose cartridge and dry powder inhaler |
| US7305986B1 (en) | 1999-07-23 | 2007-12-11 | Mannkind Corporation | Unit dose capsules for use in a dry powder inhaler |
| US7022674B2 (en) * | 1999-12-16 | 2006-04-04 | Eli Lilly And Company | Polypeptide compositions with improved stability |
| WO2001051071A2 (en) * | 2000-01-11 | 2001-07-19 | Novo Nordisk A/S | Transepithelial delivery of glp-1 derivatives |
| US6540982B1 (en) * | 2000-01-25 | 2003-04-01 | Aeropharm Technology Incorporated | Medical aerosol formulation |
| US6540983B1 (en) * | 2000-01-25 | 2003-04-01 | Aeropharm Technology Incorporated | Medical aerosol formulation |
| US6608038B2 (en) * | 2000-03-15 | 2003-08-19 | Novartis Ag | Methods and compositions for treatment of diabetes and related conditions via gene therapy |
| US6447750B1 (en) * | 2000-05-01 | 2002-09-10 | Aeropharm Technology Incorporated | Medicinal aerosol formulation |
| US6468507B1 (en) * | 2000-05-01 | 2002-10-22 | Aeropharm Technology, Inc. | Non-aqueous aerosol formulation comprising rosiglitazone maleate, a non-aqueous carrier, and an amino acid stabilizer |
| JP4716641B2 (ja) * | 2000-06-16 | 2011-07-06 | イーライ リリー アンド カンパニー | グルカゴン様ペプチド−１類似体 |
| US6562807B2 (en) * | 2000-06-23 | 2003-05-13 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
| AU2001268958B2 (en) * | 2000-07-04 | 2006-03-09 | Novo Nordisk A/S | Heterocyclic compounds, which are inhibitors of the enzyme dpp-iv |
| AU3938402A (en) * | 2000-12-13 | 2002-06-24 | Lilly Co Eli | Chronic treatment regimen using glucagon-like insulinotropic peptides |
| AU2002254567B2 (en) * | 2001-04-11 | 2007-10-11 | Bristol-Myers Squibb Company | Amino acid complexes of C-aryl glucosides for treatment of diabetes and method |
| US7232897B2 (en) * | 2001-04-24 | 2007-06-19 | Harvard University, President And Fellows Of Harvard College | Compositions and methods for modulating NH2-terminal Jun Kinase activity |
| AU2002308706A1 (en) * | 2001-06-01 | 2002-12-16 | Eli Lilly And Company | Glp-1 formulations with protracted time action |
| AU2002322403A1 (en) * | 2001-08-23 | 2003-03-10 | Eli Lilly And Company | Glucagon-like peptide-1 analogs |
| EP1432430A4 (en) * | 2001-08-28 | 2006-05-10 | Lilly Co Eli | PREMIXTURES OF GLP-1 AND BASALINSULIN |
| MXPA04003569A (es) * | 2001-10-19 | 2004-07-23 | Lilly Co Eli | Mezclas bifasicas de glp-1 e insulina. |
| US20040038865A1 (en) | 2002-08-01 | 2004-02-26 | Mannkind Corporation | Cell transport compositions and uses thereof |
| US20080260838A1 (en) | 2003-08-01 | 2008-10-23 | Mannkind Corporation | Glucagon-like peptide 1 (glp-1) pharmaceutical formulations |
| US20040121964A1 (en) * | 2002-09-19 | 2004-06-24 | Madar David J. | Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV) |
| US9078866B2 (en) * | 2003-08-01 | 2015-07-14 | Mannkind Corporation | Method for treating hyperglycemia with GLP-1 |
| JP3903061B2 (ja) * | 2003-12-24 | 2007-04-11 | 株式会社Ｌｔｔバイオファーマ | 薬物を含有するナノ粒子およびその製造方法、ならびに当該ナノ粒子からなる非経口投与用製剤 |
| JP2007536268A (ja) * | 2004-05-06 | 2007-12-13 | エミスフェアー・テクノロジーズ・インク | 固体剤形の湿性ヘパリン |
| PL1786784T3 (pl) | 2004-08-20 | 2011-04-29 | Mannkind Corp | Kataliza syntezy diketopiperazyn |
| BRPI0514410A (pt) | 2004-08-23 | 2008-06-10 | Mannkind Corp | fornecimento pulmonar de inibidores de fosfodiesterase do tipo 5 |
| KR101644250B1 (ko) | 2004-08-23 | 2016-07-29 | 맨카인드 코포레이션 | 약물 전달용 디케토피페라진염, 디케토모르포린염 또는 디케토디옥산염 |
| KR20070095927A (ko) * | 2004-12-03 | 2007-10-01 | 메데리오 에이지 | 폐 흡입을 위한 글루카곤-형 펩타이드 약제를 포함하는의약품 |
| SE0402976L (sv) * | 2004-12-03 | 2006-06-04 | Mederio Ag | Medicinsk produkt |
| JP2008526893A (ja) * | 2005-01-10 | 2008-07-24 | マンカインド コーポレイション | 肺における吸入可能なインスリンの自然増加を最少化するための方法及び組成物 |
| WO2007030706A1 (en) | 2005-09-08 | 2007-03-15 | New England Medical Center Hospitals, Inc. | Fragments of the glucagon-like peptide-i and uses thereof |
| CN104324362B (zh) | 2005-09-14 | 2018-04-24 | 曼金德公司 | 以提高活性试剂对结晶微粒表面的亲和力为基础的药物配制方法 |
| EP2364735A3 (en) * | 2005-12-16 | 2012-04-11 | Nektar Therapeutics | Branched PEG conjugates of GLP-1 |
| IN2015DN00888A (https=) | 2006-02-22 | 2015-07-10 | Mannkind Corp | |
| KR101438839B1 (ko) * | 2006-04-14 | 2014-10-02 | 맨카인드 코포레이션 | 글루카곤 유사 펩타이드 1 （ｇｌｐ-1） 약제학적 제제 |
| CA2677932A1 (en) * | 2007-02-15 | 2008-08-21 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| JP2011500850A (ja) | 2007-10-24 | 2011-01-06 | マンカインド コーポレイション | Ｇｌｐ−１による副作用を防止する方法 |
| WO2009055742A2 (en) * | 2007-10-24 | 2009-04-30 | Mannkind Corporation | Delivery of active agents |
| EP2060268A1 (en) | 2007-11-15 | 2009-05-20 | Novo Nordisk A/S | Pharmaceutical compositions for pulmonary or nasal delivery of peptides |
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2008
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- 2008-10-24 RU RU2010120666/15A patent/RU2474415C2/ru not_active IP Right Cessation
- 2008-10-24 CA CA2703338A patent/CA2703338A1/en not_active Abandoned
- 2008-10-24 PL PL08841194T patent/PL2211842T3/pl unknown
- 2008-10-24 MX MX2010004510A patent/MX2010004510A/es active IP Right Grant
- 2008-10-24 KR KR1020137027725A patent/KR101736535B1/ko not_active Expired - Fee Related
- 2008-10-24 US US12/258,340 patent/US8377869B2/en active Active
- 2008-10-24 AU AU2008316634A patent/AU2008316634B2/en not_active Ceased
- 2008-10-24 HU HUE08841194A patent/HUE025485T2/en unknown
- 2008-10-24 BR BRPI0818872 patent/BRPI0818872A2/pt not_active IP Right Cessation
- 2008-10-24 KR KR1020107011096A patent/KR101736502B1/ko not_active Expired - Fee Related
- 2008-10-24 WO PCT/US2008/081218 patent/WO2009055740A2/en not_active Ceased
- 2008-10-24 EP EP08841194.7A patent/EP2211842B1/en not_active Not-in-force
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- 2008-10-24 DK DK08841194.7T patent/DK2211842T3/en active
- 2008-10-24 ES ES08841194.7T patent/ES2547529T3/es active Active
- 2008-10-24 EP EP15178836.1A patent/EP2954893A1/en not_active Withdrawn
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2012
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2013
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2014
- 2014-05-20 AU AU2014202731A patent/AU2014202731A1/en not_active Abandoned
- 2014-09-18 JP JP2014190113A patent/JP2015013892A/ja active Pending
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2020
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2022
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Also Published As
| Publication number | Publication date |
|---|---|
| US8377869B2 (en) | 2013-02-19 |
| DK2211842T3 (en) | 2015-09-21 |
| JP2011500850A (ja) | 2011-01-06 |
| BRPI0818872A2 (pt) | 2015-05-05 |
| RU2474415C2 (ru) | 2013-02-10 |
| US20220387593A1 (en) | 2022-12-08 |
| WO2009055740A3 (en) | 2009-06-11 |
| HUE025485T2 (en) | 2016-02-29 |
| RU2010120666A (ru) | 2011-11-27 |
| US20090110647A1 (en) | 2009-04-30 |
| KR20100093055A (ko) | 2010-08-24 |
| AU2008316634A1 (en) | 2009-04-30 |
| RU2012146344A (ru) | 2014-05-10 |
| EP2211842A2 (en) | 2010-08-04 |
| US20200147219A1 (en) | 2020-05-14 |
| KR101736535B1 (ko) | 2017-05-16 |
| EP2954893A1 (en) | 2015-12-16 |
| EP2211842B1 (en) | 2015-08-12 |
| CA2703338A1 (en) | 2009-04-30 |
| AU2014202731A1 (en) | 2014-06-12 |
| KR20130123467A (ko) | 2013-11-12 |
| US20130125886A1 (en) | 2013-05-23 |
| MX2010004510A (es) | 2010-07-02 |
| KR101736502B1 (ko) | 2017-05-16 |
| PL2211842T3 (pl) | 2015-12-31 |
| AU2008316634B2 (en) | 2014-02-27 |
| WO2009055740A2 (en) | 2009-04-30 |
| JP2015013892A (ja) | 2015-01-22 |
| CN101969927A (zh) | 2011-02-09 |
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