BE1012957A5 - Articles de fabrication. - Google Patents
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- Publication number
- BE1012957A5 BE1012957A5 BE2000/0295A BE200000295A BE1012957A5 BE 1012957 A5 BE1012957 A5 BE 1012957A5 BE 2000/0295 A BE2000/0295 A BE 2000/0295A BE 200000295 A BE200000295 A BE 200000295A BE 1012957 A5 BE1012957 A5 BE 1012957A5
- Authority
- BE
- Belgium
- Prior art keywords
- sep
- pde5
- pde5 inhibitor
- treatment
- inhibitor
- Prior art date
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Formation And Processing Of Food Products (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Mechanical Treatment Of Semiconductor (AREA)
- Glass Compositions (AREA)
- Enzymes And Modification Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US13203699P | 1999-04-30 | 1999-04-30 |
Publications (1)
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|---|---|
| BE1012957A5 true BE1012957A5 (fr) | 2001-06-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| BE2000/0295A BE1012957A5 (fr) | 1999-04-30 | 2000-04-26 | Articles de fabrication. |
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Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1200090B1 (en) * | 1999-08-03 | 2013-09-11 | ICOS Corporation | Pharmaceutical formulation comprising a beta-carboline and its use for treating sexual dysfunction |
| DE10010612A1 (de) * | 2000-03-03 | 2001-09-27 | Merck Patent Gmbh | Verwendung von PDE V-Inhibitoren |
| JP2004533402A (ja) * | 2000-06-08 | 2004-11-04 | リリー アイコス リミテッド ライアビリティ カンパニー | Ｐｄｅｖインヒビターとしての四環系ジケトピペラジン化合物 |
| CA2423357C (en) | 2000-08-02 | 2008-05-27 | Lilly Icos Llc | Fused heterocyclic derivatives as phosphodiesterase inhibitors |
| ES2286291T3 (es) | 2001-06-05 | 2007-12-01 | Lilly Icos Llc | Compustos tetraciclicos como inhibidores de pde5. |
| GB0129274D0 (en) * | 2001-12-06 | 2002-01-23 | Pfizer Ltd | Novel kit |
| US20060205733A1 (en) * | 2004-08-26 | 2006-09-14 | Encysive Pharmaceuticals | Endothelin a receptor antagonists in combination with phosphodiesterase 5 inhibitors and uses thereof |
| MX2008012495A (es) | 2006-03-28 | 2009-01-07 | Javelin Pharmaceuticals Inc | Formulaciones de dosis baja de diclofenaco y beta-ciclodextrina. |
| US7495024B2 (en) | 2006-08-07 | 2009-02-24 | Via Pharmaceuticals, Inc. | Phenylalkyl N-hydroxyureas for combating atherosclerotic plaque |
| DE102007028869A1 (de) | 2007-06-22 | 2008-12-24 | Ratiopharm Gmbh | Verfahren zur Herstellung eines Arzneimittels enthaltend Tadalafil |
| DE102009033396A1 (de) | 2009-07-16 | 2011-01-20 | Ratiopharm Gmbh | Wässrige Lösung und gelatinierte Zusammensetzung umfassend einen Phosphodiesterase-5-Inhibitor sowie diesbezügliche Verfahren und Verwendung |
| US10610528B2 (en) | 2009-12-08 | 2020-04-07 | Intelgenx Corp. | Solid oral film dosage forms and methods for making same |
| US20110136815A1 (en) | 2009-12-08 | 2011-06-09 | Horst Zerbe | Solid oral film dosage forms and methods for making same |
| US20110263606A1 (en) * | 2010-04-26 | 2011-10-27 | Horst Zerbe | Solid oral dosage forms comprising tadalafil |
| EP2672959A1 (en) | 2011-02-10 | 2013-12-18 | Synthon BV | Granulated composition comprising tadalafil and a disintegrant |
| WO2012107541A1 (en) | 2011-02-10 | 2012-08-16 | Synthon Bv | Pharmaceutical composition comprising tadalafil and a cyclodextrin |
| WO2012107092A1 (en) | 2011-02-10 | 2012-08-16 | Synthon Bv | Pharmaceutical composition comprising tadalafil and a cyclodextrin |
| KR102239291B1 (ko) | 2013-06-28 | 2021-04-14 | 한미약품 주식회사 | 타다라필 또는 이의 약학적으로 허용가능한 염을 포함하는 저작정 제제 |
| KR101663238B1 (ko) | 2013-11-15 | 2016-10-14 | 한미약품 주식회사 | 타다라필 및 암로디핀을 포함하는 복합 고형 제제 |
| KR102646431B1 (ko) | 2017-09-29 | 2024-03-12 | 한미약품 주식회사 | 생산성 및 균일성이 개선된 타다라필을 함유하는 고형제제 및 그 제조방법 |
| US20210137919A1 (en) * | 2018-02-07 | 2021-05-13 | Smawa Gmbh | Pharmaceutical formulations, method for producing a pharmaceutical formulation, and medicament comprising same |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995019978A1 (en) * | 1994-01-21 | 1995-07-27 | Laboratoires Glaxo Wellcome S.A. | Tetracyclic derivatives, process of preparation and use |
| WO1997003985A1 (en) * | 1995-07-14 | 1997-02-06 | Icos Corporation | Cyclic gmp-specific phosphodiesterase inhibitors |
| WO1997003675A1 (en) * | 1995-07-14 | 1997-02-06 | Icos Corporation | Use of cgmp-phosphodiesterase inhibitors to treat impotence |
| WO1999059584A1 (en) * | 1998-05-20 | 1999-11-25 | Schering Corporation | Combination of phentolamine and cyclic gmp phosphodiesterase inhibitors for the treatment of sexual dysfunction |
| WO2000020033A1 (fr) * | 1998-10-05 | 2000-04-13 | Eisai Co., Ltd. | Comprimes se delitant immediatement dans la cavite buccale |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9301192D0 (en) * | 1993-06-09 | 1993-06-09 | Trott Francis W | Flower shaped mechanised table |
| GB9423911D0 (en) * | 1994-11-26 | 1995-01-11 | Pfizer Ltd | Therapeutic agents |
| GB9511220D0 (en) * | 1995-06-02 | 1995-07-26 | Glaxo Group Ltd | Solid dispersions |
| GB9514473D0 (en) * | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Chemical compounds |
| IL126951A0 (en) | 1996-05-10 | 1999-09-22 | Icos Corp | Carboline derivatives |
| CA2288910C (en) * | 1997-04-25 | 2003-06-24 | Pfizer Inc. | Pyrazolopyrimidinones for sexual dysfunction |
| AU1025899A (en) | 1998-09-16 | 2000-04-03 | Icos Corporation | Carboline derivatives as cgmp phosphodiesterase inhibitors |
| EP1161255A4 (en) * | 1999-03-08 | 2002-07-17 | Merck & Co Inc | METHOD AND MEANS FOR TREATING ERECTILE DYSFUNCTION |
| CA2365782A1 (en) * | 1999-04-30 | 2000-11-09 | William E. Pullman | Treatment of female arousal disorder |
| US6451807B1 (en) * | 1999-04-30 | 2002-09-17 | Lilly Icos, Llc. | Methods of treating sexual dysfunction in an individual suffering from a retinal disease, class 1 congestive heart failure, or myocardial infarction using a PDE5 inhibitor |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995019978A1 (en) * | 1994-01-21 | 1995-07-27 | Laboratoires Glaxo Wellcome S.A. | Tetracyclic derivatives, process of preparation and use |
| WO1997003985A1 (en) * | 1995-07-14 | 1997-02-06 | Icos Corporation | Cyclic gmp-specific phosphodiesterase inhibitors |
| WO1997003675A1 (en) * | 1995-07-14 | 1997-02-06 | Icos Corporation | Use of cgmp-phosphodiesterase inhibitors to treat impotence |
| WO1999059584A1 (en) * | 1998-05-20 | 1999-11-25 | Schering Corporation | Combination of phentolamine and cyclic gmp phosphodiesterase inhibitors for the treatment of sexual dysfunction |
| WO2000020033A1 (fr) * | 1998-10-05 | 2000-04-13 | Eisai Co., Ltd. | Comprimes se delitant immediatement dans la cavite buccale |
Non-Patent Citations (3)
| Title |
|---|
| DATABASE WPI Section Ch Week 200029, Derwent World Patents Index; Class B02, AN 2000-339026, XP002152606 * |
| GOLDENBERG M M: "SAFETY AND EFFICACY OF SILDENAFIL CITRATE IN THE TREATMENT OF MALE ERECTILE DYSFUNCTION", CLINICAL THERAPEUTICS,US,EXCERPTA MEDICA, PRINCETON, NJ, vol. 20, no. 6, 1998, pages 1033 - 1048, XP000853855, ISSN: 0149-2918 * |
| ISRAEL M: "VIAGRA: THE FIRST ORAL TREATMENT FOR IMPOTENCE", PHARMACEUTICAL JOURNAL,PHARMACEUTICAL SOCIETY, LONDON,GB, vol. 261, 1 August 1998 (1998-08-01), pages 164 - 165, XP000919343, ISSN: 0031-6873 * |
Also Published As
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| BE1012957A5 (fr) | Articles de fabrication. | |
| US6943166B1 (en) | Compositions comprising phosphodiesterase inhabitors for the treatment of sexual disfunction | |
| US6451807B1 (en) | Methods of treating sexual dysfunction in an individual suffering from a retinal disease, class 1 congestive heart failure, or myocardial infarction using a PDE5 inhibitor | |
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| CZ20001536A3 (cs) | Orální léčivo |
Legal Events
| Date | Code | Title | Description |
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| RE | Patent lapsed |
Effective date: 20040430 |