JP5091106B2 - 真性糖尿病の治療のためのロフルミラスト - Google Patents
真性糖尿病の治療のためのロフルミラスト Download PDFInfo
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- JP5091106B2 JP5091106B2 JP2008500172A JP2008500172A JP5091106B2 JP 5091106 B2 JP5091106 B2 JP 5091106B2 JP 2008500172 A JP2008500172 A JP 2008500172A JP 2008500172 A JP2008500172 A JP 2008500172A JP 5091106 B2 JP5091106 B2 JP 5091106B2
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- diabetes
- pharmaceutically acceptable
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- acceptable salt
- treatment
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Landscapes
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| ATE409057T1 (de) | 2002-02-11 | 2008-10-15 | Antares Pharma Inc | Intradermales injektionsgerät |
| JP5216328B2 (ja) | 2005-01-24 | 2013-06-19 | アンタレス ファーマ インコーポレイテッド | あらかじめ充填された針補助シリンジジェット式注射器 |
| CN101137368B (zh) * | 2005-03-08 | 2012-05-16 | 奈科明有限责任公司 | 治疗糖尿病的罗氟司特 |
| TW200738266A (en) * | 2005-09-29 | 2007-10-16 | Sankyo Co | Pharmaceutical agent containing insulin resistance improving agent |
| WO2007131025A1 (en) | 2006-05-03 | 2007-11-15 | Antares Pharma, Inc. | Injector with adjustable dosing |
| WO2007131013A1 (en) | 2006-05-03 | 2007-11-15 | Antares Pharma, Inc. | Two-stage reconstituting injector |
| AU2007293885A1 (en) * | 2006-09-07 | 2008-03-13 | Takeda Gmbh | Combination treatment for diabetes mellitus |
| ES2752152T3 (es) | 2008-03-10 | 2020-04-03 | Antares Pharma Inc | Dispositivo de seguridad para inyector |
| CN101548972B (zh) * | 2008-04-03 | 2012-10-17 | 万特制药(海南)有限公司 | 一种含有瑞格列奈的固体药物组合物 |
| ES2738539T3 (es) | 2008-08-05 | 2020-01-23 | Antares Pharma Inc | Inyector de dosis múltiples |
| EP4427737A3 (en) | 2009-03-20 | 2024-11-20 | Antares Pharma, Inc. | Hazardous agent injection system |
| US8496619B2 (en) | 2011-07-15 | 2013-07-30 | Antares Pharma, Inc. | Injection device with cammed ram assembly |
| US9220660B2 (en) | 2011-07-15 | 2015-12-29 | Antares Pharma, Inc. | Liquid-transfer adapter beveled spike |
| US20130172303A1 (en) * | 2012-01-03 | 2013-07-04 | Forest Laboratories Holdings Ltd. | Roflumilast compositions for the treatment of copd |
| US9486583B2 (en) | 2012-03-06 | 2016-11-08 | Antares Pharma, Inc. | Prefilled syringe with breakaway force feature |
| CN104487114A (zh) | 2012-04-06 | 2015-04-01 | 安塔雷斯药品公司 | 针头辅助喷射注射给予睾酮组合物 |
| WO2013169804A1 (en) | 2012-05-07 | 2013-11-14 | Antares Pharma, Inc. | Needle assisted jet injection device having reduced trigger force |
| ES2969984T3 (es) | 2013-02-11 | 2024-05-23 | Antares Pharma Inc | Dispositivo de inyección por chorro asistido por aguja que tiene fuerza de disparo reducida |
| WO2014124860A1 (en) | 2013-02-14 | 2014-08-21 | Boehringer Ingelheim International Gmbh | Specific pde4b-inhibitors for the treatment of diabetes mellitus |
| WO2014164786A1 (en) * | 2013-03-11 | 2014-10-09 | Madsen Patrick | Dosage injector with pinion system |
| WO2014165136A1 (en) | 2013-03-12 | 2014-10-09 | Antares Pharma, Inc. | Constant volume prefilled syringes and kits thereof |
| EP3165224A1 (en) * | 2015-11-09 | 2017-05-10 | Albert-Ludwigs-Universität Freiburg | Use of pde4 inhibitors for the prophylaxis and/or therapy of dyslipoproteinaemia and related disorders |
| CN109328193A (zh) | 2016-04-19 | 2019-02-12 | 尤瑞卡有限公司 | 肽-低聚脲折叠体化合物及其使用方法 |
| GB202306663D0 (en) * | 2023-05-05 | 2023-06-21 | Union Therapeutics As | Combination therapy |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3174901A (en) * | 1963-01-31 | 1965-03-23 | Jan Marcel Didier Aron Samuel | Process for the oral treatment of diabetes |
| JPS5869812A (ja) | 1981-10-22 | 1983-04-26 | Chugai Pharmaceut Co Ltd | 血糖降下剤 |
| AR240698A1 (es) * | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
| IL87149A (en) | 1987-07-20 | 1994-05-30 | Merck & Co Inc | 6-Piperazinyl derivatives of purine and its 3- and 9-deaza isosteres, their preparation and pharmaceutical compositions containing them |
| US5698711A (en) * | 1991-01-28 | 1997-12-16 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| GB9215633D0 (en) | 1992-07-23 | 1992-09-09 | Smithkline Beecham Plc | Novel treatment |
| JP3775684B2 (ja) | 1992-07-28 | 2006-05-17 | ローン−プーラン・ロレ・リミテツド | 脂肪族−またはヘテロ原子−含有連結基によりアリールまたはヘテロアリールに連結されたフェニル含有化合物 |
| WO1994008609A1 (en) * | 1992-10-15 | 1994-04-28 | Dana-Farber Cancer Institute, Inc. | TREATMENT OF INSULIN RESISTANCE IN OBESITY LINKED TYPE II DIABETES USING ANTAGONISTS TO TNF-α FUNCTION |
| SI0706513T1 (en) * | 1993-07-02 | 2002-10-31 | Altana Pharma Ag | Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors |
| US5817670A (en) * | 1994-08-29 | 1998-10-06 | Yamanouchi Pharmaceutical Co., Ltd. | Naphthyridine derivatives and pharmaceutical compositions thereof |
| ATE233735T1 (de) * | 1996-01-31 | 2003-03-15 | Altana Pharma Ag | Neue phenanthridine |
| DE19617864A1 (de) * | 1996-04-23 | 1997-10-30 | Schering Ag | Neue chirale Phenyldihydrofuranone |
| US6331543B1 (en) * | 1996-11-01 | 2001-12-18 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
| JP2001516765A (ja) * | 1997-09-12 | 2001-10-02 | ヴォルフ ゲオルグ フォースマン | 真性糖尿病及び肥満の治療のための組成物 |
| SE9801992D0 (sv) * | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl-2-hydroxypropionic acid derivative I |
| ES2241571T3 (es) | 1999-01-15 | 2005-11-01 | Altana Pharma Ag | N-oxidos de fenantrinida con actividad inhividora de pde-iv. |
| EP1147089B1 (en) | 1999-01-15 | 2005-12-07 | ALTANA Pharma AG | Phenylphenanthridines with pde-iv inhibiting activity |
| US7323496B2 (en) * | 1999-11-08 | 2008-01-29 | Theracos, Inc. | Compounds for treatment of inflammation, diabetes and related disorders |
| AU3270301A (en) | 1999-11-13 | 2001-05-30 | Icos Corporation | Combined pde3 and pde4 inhibitor therapy for the treatment of obesity |
| CA2393650C (en) | 1999-12-08 | 2010-06-15 | Grelan Pharmaceutical Co., Ltd. | Novel 1,8-naphthyridin-2(1h)-one derivatives |
| AU2001250820A1 (en) * | 2000-03-13 | 2001-09-24 | Ortho-Mcneil Pharmaceutical, Inc. | Novel cyclohexene derivatives useful as antagonists of the motilin receptor |
| CA2404226A1 (en) | 2000-03-23 | 2001-09-27 | Takeda Chemical Industries, Ltd. | Furoisoquinoline derivatives, process for producing the same and use thereof |
| CA2407780A1 (en) | 2000-05-25 | 2001-11-29 | Merck Frosst Canada & Co./Merck Frosst Canada & Cie | Fluoroalkoxy-substituted benzamide dichloropyridinyl n-oxide pde4 inhibitor |
| RU2275359C2 (ru) | 2000-08-11 | 2006-04-27 | Оно Фармасьютикал Ко., Лтд. | Производные пиперидина и средство, содержащее производное пиперидина в качестве активного ингредиента |
| WO2002013798A2 (en) | 2000-08-11 | 2002-02-21 | Pfizer Limited | Treatment of the insulin resistance syndrome with selective cgmp pde5 inhibitors |
| HUP0302793A3 (en) | 2001-01-22 | 2006-01-30 | Memory Pharmaceuticals Corp Mo | N-substituted aniline derivatives useful as phosphodiesterase 4 inhibitors, pharmaceutical compositions containing them and process for their preparations |
| HUP0302891A2 (hu) * | 2001-01-31 | 2003-12-29 | Pfizer Products Inc. | PDE4 izoenzimek inhibitoraiként alkalmazható éterszármazékok, alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények |
| WO2002060898A1 (en) * | 2001-01-31 | 2002-08-08 | Pfizer Products Inc. | Thiazolyl-, oxazolyl-, pyrrolyl-, and imidazolyl-acid amide derivatives useful as inhibitors of pde4 isozymes |
| WO2002064584A1 (en) | 2001-02-15 | 2002-08-22 | Altana Pharma Ag | Phthalayinone-piperidino-derivatives as pde4 inhibitors |
| EP1370211A4 (en) * | 2001-03-02 | 2005-02-09 | Bristol Myers Squibb Co | SIMULTANEOUS ADMINISTRATION OF MELANOCORTIN RECEPTOR AGONISTS AND A PHOSPHODIESTERASE HEMMER FOR THE TREATMENT OF DISEASES RELATED TO CYCLIC AMP |
| UA74912C2 (en) * | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
| DE10150517A1 (de) | 2001-10-12 | 2003-04-17 | Merck Patent Gmbh | Verwendung von Phosphodiesterase IV-Inhibitoren |
| US20030181461A1 (en) | 2002-01-25 | 2003-09-25 | Lautt Wilfred Wayne | Use of phosphodiesterase antagonists to treat insulin resistance |
| BR0311337A (pt) * | 2002-05-28 | 2005-03-15 | Altana Pharma Ag | Uso oftalmológico de roflumilast para o tratamento de doenças do olho |
| WO2004016596A1 (en) | 2002-08-19 | 2004-02-26 | Glenmark Pharmaceuticals Limited | Condensed heterocyclic compounds as pde-iv inhibitors for the treatment of inflammatory and allergic disorders |
| WO2004067006A1 (en) * | 2003-01-27 | 2004-08-12 | Pharmacia Corporation | Combination of a pde iv inhibitor and a tnf-alpha antagonist |
| WO2004098597A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | Composition comprising roflumilast and shuil-1r ii |
| WO2004098598A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | COMPOSITION COMPRISING ROFLUMILAST AND A TNFα ANTAGONIST |
| WO2004098595A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | COMPOSITION COMPRISING ROFLUMILAST AND A TNFα ANTAGONIST |
| WO2004098596A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | Composition comprising roflumilast and il-1 trap |
| RS52730B (sr) | 2003-05-22 | 2013-08-30 | Takeda Gmbh | Kompozicija koja sadrži pde4 inhibitor i pde5 inhibitor |
| WO2005020926A2 (en) * | 2003-08-28 | 2005-03-10 | Pharmacia Corporation | Treatment or prevention of vascular disorders with cox-2 inhibitors in combination with cyclic amp-specific phosphodiesterase inhibitors |
| WO2005023253A1 (en) * | 2003-09-05 | 2005-03-17 | Altana Pharma Ag | Use of pde4 inhibitors for the treatment of diabetes mellitus |
| MXPA06004499A (es) | 2003-10-21 | 2006-06-27 | Pharmacia Corp | Metodo para el tratamiento o la prevencion de inflamacion respiratoria con un inhibidor de ciclooxigenasa 2 en combinacion con un inhibidor de fosfodiesterasa 4 y sus composiciones. |
| TW200539867A (en) | 2004-04-13 | 2005-12-16 | Arena Pharm Inc | Human g protein-coupled receptor and modulators thereof for the treatment of hyperglycemia and related disorders |
| CN101137368B (zh) * | 2005-03-08 | 2012-05-16 | 奈科明有限责任公司 | 治疗糖尿病的罗氟司特 |
-
2006
- 2006-03-03 CN CN2006800072465A patent/CN101137368B/zh not_active Expired - Fee Related
- 2006-03-03 KR KR1020077022434A patent/KR101302838B1/ko not_active Expired - Fee Related
- 2006-03-03 NZ NZ560269A patent/NZ560269A/en not_active IP Right Cessation
- 2006-03-03 EA EA200701845A patent/EA015382B1/ru not_active IP Right Cessation
- 2006-03-03 CA CA2599376A patent/CA2599376C/en not_active Expired - Fee Related
- 2006-03-03 AU AU2006222060A patent/AU2006222060B2/en not_active Ceased
- 2006-03-03 CN CN2012100579547A patent/CN102600144A/zh active Pending
- 2006-03-03 EP EP06708617A patent/EP1874308A1/en not_active Withdrawn
- 2006-03-03 US US11/885,450 patent/US8017633B2/en not_active Expired - Fee Related
- 2006-03-03 WO PCT/EP2006/060418 patent/WO2006094933A1/en not_active Ceased
- 2006-03-03 BR BRPI0609371-0A patent/BRPI0609371A2/pt not_active IP Right Cessation
- 2006-03-03 MX MX2007010560A patent/MX2007010560A/es not_active Application Discontinuation
- 2006-03-03 JP JP2008500172A patent/JP5091106B2/ja not_active Expired - Fee Related
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- 2007-07-27 ZA ZA200706294A patent/ZA200706294B/xx unknown
- 2007-08-14 IL IL185277A patent/IL185277A/en not_active IP Right Cessation
- 2007-10-01 NO NO20074943A patent/NO20074943L/no not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| NZ560269A (en) | 2010-12-24 |
| CA2599376A1 (en) | 2006-09-14 |
| JP5611275B2 (ja) | 2014-10-22 |
| JP2008532974A (ja) | 2008-08-21 |
| NO20074943L (no) | 2007-10-01 |
| EA200701845A1 (ru) | 2008-02-28 |
| US8017633B2 (en) | 2011-09-13 |
| CA2599376C (en) | 2014-05-13 |
| CN101137368B (zh) | 2012-05-16 |
| US20110269750A1 (en) | 2011-11-03 |
| KR20070111539A (ko) | 2007-11-21 |
| HK1116077A1 (en) | 2008-12-19 |
| MX2007010560A (es) | 2008-02-21 |
| EP1874308A1 (en) | 2008-01-09 |
| BRPI0609371A2 (pt) | 2010-03-30 |
| ZA200706294B (en) | 2008-09-25 |
| KR101302838B1 (ko) | 2013-09-03 |
| US8541456B2 (en) | 2013-09-24 |
| CN102600144A (zh) | 2012-07-25 |
| EA015382B1 (ru) | 2011-08-30 |
| AU2006222060A1 (en) | 2006-09-14 |
| US20080214625A1 (en) | 2008-09-04 |
| JP2012188448A (ja) | 2012-10-04 |
| IL221006A0 (en) | 2012-08-30 |
| IL185277A (en) | 2013-08-29 |
| CN101137368A (zh) | 2008-03-05 |
| AU2006222060B2 (en) | 2011-09-01 |
| IL185277A0 (en) | 2008-02-09 |
| WO2006094933A1 (en) | 2006-09-14 |
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