JP4819224B2 - ベンゾインデンプロスタグランジンの吸入送達法 - Google Patents
ベンゾインデンプロスタグランジンの吸入送達法 Download PDFInfo
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- JP4819224B2 JP4819224B2 JP2000604834A JP2000604834A JP4819224B2 JP 4819224 B2 JP4819224 B2 JP 4819224B2 JP 2000604834 A JP2000604834 A JP 2000604834A JP 2000604834 A JP2000604834 A JP 2000604834A JP 4819224 B2 JP4819224 B2 JP 4819224B2
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- Prior art keywords
- prostaglandin
- benzoindene
- trinol
- methano
- deoxy
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- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Dispersion Chemistry (AREA)
- Otolaryngology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12499999P | 1999-03-18 | 1999-03-18 | |
| US60/124,999 | 1999-03-18 | ||
| PCT/US2000/040040 WO2000054758A2 (en) | 1999-03-18 | 2000-03-17 | Method for delivering benzidine prostaglandins by inhalation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011119894A Division JP2011201907A (ja) | 1999-03-18 | 2011-05-30 | ベンゾインデンプロスタグランジンの吸入送達法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002539154A JP2002539154A (ja) | 2002-11-19 |
| JP4819224B2 true JP4819224B2 (ja) | 2011-11-24 |
Family
ID=22417774
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000604834A Expired - Lifetime JP4819224B2 (ja) | 1999-03-18 | 2000-03-17 | ベンゾインデンプロスタグランジンの吸入送達法 |
| JP2011119894A Pending JP2011201907A (ja) | 1999-03-18 | 2011-05-30 | ベンゾインデンプロスタグランジンの吸入送達法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011119894A Pending JP2011201907A (ja) | 1999-03-18 | 2011-05-30 | ベンゾインデンプロスタグランジンの吸入送達法 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6521212B1 (enExample) |
| EP (1) | EP1161234B1 (enExample) |
| JP (2) | JP4819224B2 (enExample) |
| KR (1) | KR100750384B1 (enExample) |
| CN (1) | CN1196479C (enExample) |
| AT (1) | ATE245979T1 (enExample) |
| AU (1) | AU4082700A (enExample) |
| CA (1) | CA2365890C (enExample) |
| DE (1) | DE60004181T2 (enExample) |
| DK (1) | DK1161234T3 (enExample) |
| ES (1) | ES2203449T3 (enExample) |
| PT (1) | PT1161234E (enExample) |
| WO (1) | WO2000054758A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11660304B2 (en) | 2016-05-05 | 2023-05-30 | Liquidia Technologies, Inc. | Dry powder treprostinil for the treatment of pulmonary hypertension |
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| US6521212B1 (en) * | 1999-03-18 | 2003-02-18 | United Therapeutics Corporation | Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation |
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| US8912174B2 (en) | 2003-04-16 | 2014-12-16 | Mylan Pharmaceuticals Inc. | Formulations and methods for treating rhinosinusitis |
| US9808471B2 (en) | 2003-04-16 | 2017-11-07 | Mylan Specialty Lp | Nasal pharmaceutical formulations and methods of using the same |
| US7811606B2 (en) | 2003-04-16 | 2010-10-12 | Dey, L.P. | Nasal pharmaceutical formulations and methods of using the same |
| ES2670872T3 (es) * | 2003-05-22 | 2018-06-01 | United Therapeutics Corporation | Polimorfo de una sal de dietanolamina de treprostinil |
| US20040265238A1 (en) * | 2003-06-27 | 2004-12-30 | Imtiaz Chaudry | Inhalable formulations for treating pulmonary hypertension and methods of using same |
| US7442372B2 (en) | 2003-08-29 | 2008-10-28 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| JP4906514B2 (ja) * | 2003-12-16 | 2012-03-28 | ユナイテッド セラピューティクス コーポレイション | 腎臓機能改善のためのトレプロスチニルの用途 |
| US20090124697A1 (en) * | 2003-12-16 | 2009-05-14 | United Therapeutics Corporation | Inhalation formulations of treprostinil |
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| EP1819340A2 (en) * | 2004-12-08 | 2007-08-22 | Biomarin Pharmaceutical Inc. | Methods and compositions for the treatment of pulmonary hypertension of the newborn |
| AU2006321942A1 (en) * | 2005-12-05 | 2007-06-14 | Biomarin Pharmaceutical Inc. | Methods and compositions for the treatment of disease |
| US8747897B2 (en) | 2006-04-27 | 2014-06-10 | Supernus Pharmaceuticals, Inc. | Osmotic drug delivery system |
| JP5797376B2 (ja) * | 2006-05-15 | 2015-10-21 | ユナイテッド セラピューティクス コーポレーション | 定量吸入器を用いたトレプロスチニル投与 |
| DE102006026786A1 (de) | 2006-06-07 | 2007-12-13 | Joachim Kern | Dosierinhalator |
| US20090036465A1 (en) * | 2006-10-18 | 2009-02-05 | United Therapeutics Corporation | Combination therapy for pulmonary arterial hypertension |
| WO2008089148A1 (en) * | 2007-01-12 | 2008-07-24 | Biomarin Pharmaceutical Inc. | Method of treating a metabolic or neuropsychiatry disorder with a bh4 derivative prodrug |
| US20080280986A1 (en) | 2007-02-09 | 2008-11-13 | United Therapeutics Corporation | Treprostinil treatment for interstitial lung disease and asthma |
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| US20120177693A1 (en) * | 2008-09-25 | 2012-07-12 | Aradigm Corporation | Deep lung pulmonary delivery of treprostinil |
| EP2427054A4 (en) * | 2009-05-07 | 2014-01-15 | United Therapeutics Corp | SOLID COMPOSITIONS BASED ON PROSTACYCLINE ANALOGS |
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| AU2024208919A1 (en) | 2023-01-19 | 2025-07-17 | United Therapeutics Corporation | Treprostinil analogs |
| US20260041656A1 (en) | 2024-08-06 | 2026-02-12 | United Therapeutics Corporation | Treating pulmonary hypertension based on novel biomarker |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56138130A (en) * | 1980-02-28 | 1981-10-28 | Upjohn Co | Carbacycline analogues |
| US4306075A (en) * | 1980-03-28 | 1981-12-15 | The Upjohn Company | Composition and process |
| US4306076A (en) * | 1980-04-23 | 1981-12-15 | The Upjohn Company | Inter-phenylene CBA compounds |
| JPS5795920A (en) * | 1980-12-04 | 1982-06-15 | Teijin Ltd | Remedy for respiratory disease |
| US4349689A (en) * | 1980-12-22 | 1982-09-14 | The Upjohn Company | Methano carbacyclin analogs |
| JPS60208936A (ja) * | 1984-03-08 | 1985-10-21 | ジ・アツプジヨン・カンパニー | インターフエニレン・カルバサイクリン誘導体 |
| JPH0240325A (ja) * | 1988-06-17 | 1990-02-09 | Wellcome Found Ltd:The | 医薬用化合物 |
| JPH02264730A (ja) * | 1989-04-04 | 1990-10-29 | Mitsutoshi Taira | Ａｔｌｌ治療用吸入剤 |
| WO1993025198A1 (fr) * | 1992-06-12 | 1993-12-23 | Teijin Limited | Poudre ultra-fine pour inhalation et production de cette poudre |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1241324A (en) | 1984-03-08 | 1988-08-30 | Paul A. Aristoff | Interphenylene carbacyclin derivatives |
| EP0223831B1 (en) * | 1985-05-22 | 1992-07-15 | Liposome Technology, Inc. | Liposome inhalation method and system |
| GB8814438D0 (en) | 1988-06-17 | 1988-07-20 | Wellcome Found | Compounds for use in medicine |
| US5190972A (en) * | 1992-01-27 | 1993-03-02 | The University Of Melbourne | Method of combatting cyclosporine organ toxicity with prostaglandin analogs |
| KR100638684B1 (ko) * | 1997-11-14 | 2006-10-27 | 유나이티드 세러퓨틱스 코오포레이션 | 말초 혈관 질환의 치료를 위한 9-데옥시-2',9-알파-메타노-3-옥사-4,5,6-트리노르-3,7-(1',3'-인터페닐렌)-13,14-디하이드로-프로스타글란딘 에프1의 용도 |
| US6521212B1 (en) | 1999-03-18 | 2003-02-18 | United Therapeutics Corporation | Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation |
-
2000
- 2000-03-15 US US09/525,471 patent/US6521212B1/en not_active Expired - Lifetime
- 2000-03-17 WO PCT/US2000/040040 patent/WO2000054758A2/en not_active Ceased
- 2000-03-17 DK DK00920253T patent/DK1161234T3/da active
- 2000-03-17 KR KR1020017011610A patent/KR100750384B1/ko not_active Expired - Lifetime
- 2000-03-17 PT PT00920253T patent/PT1161234E/pt unknown
- 2000-03-17 AT AT00920253T patent/ATE245979T1/de active
- 2000-03-17 CN CNB008051089A patent/CN1196479C/zh not_active Expired - Lifetime
- 2000-03-17 DE DE60004181T patent/DE60004181T2/de not_active Expired - Lifetime
- 2000-03-17 ES ES00920253T patent/ES2203449T3/es not_active Expired - Lifetime
- 2000-03-17 AU AU40827/00A patent/AU4082700A/en not_active Abandoned
- 2000-03-17 EP EP00920253A patent/EP1161234B1/en not_active Expired - Lifetime
- 2000-03-17 CA CA2365890A patent/CA2365890C/en not_active Expired - Lifetime
- 2000-03-17 JP JP2000604834A patent/JP4819224B2/ja not_active Expired - Lifetime
-
2002
- 2002-08-06 US US10/212,149 patent/US6756033B2/en not_active Expired - Lifetime
-
2011
- 2011-05-30 JP JP2011119894A patent/JP2011201907A/ja active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56138130A (en) * | 1980-02-28 | 1981-10-28 | Upjohn Co | Carbacycline analogues |
| US4306075A (en) * | 1980-03-28 | 1981-12-15 | The Upjohn Company | Composition and process |
| US4306076A (en) * | 1980-04-23 | 1981-12-15 | The Upjohn Company | Inter-phenylene CBA compounds |
| JPS5795920A (en) * | 1980-12-04 | 1982-06-15 | Teijin Ltd | Remedy for respiratory disease |
| US4349689A (en) * | 1980-12-22 | 1982-09-14 | The Upjohn Company | Methano carbacyclin analogs |
| JPS60208936A (ja) * | 1984-03-08 | 1985-10-21 | ジ・アツプジヨン・カンパニー | インターフエニレン・カルバサイクリン誘導体 |
| JPH0240325A (ja) * | 1988-06-17 | 1990-02-09 | Wellcome Found Ltd:The | 医薬用化合物 |
| JPH02264730A (ja) * | 1989-04-04 | 1990-10-29 | Mitsutoshi Taira | Ａｔｌｌ治療用吸入剤 |
| WO1993025198A1 (fr) * | 1992-06-12 | 1993-12-23 | Teijin Limited | Poudre ultra-fine pour inhalation et production de cette poudre |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11660304B2 (en) | 2016-05-05 | 2023-05-30 | Liquidia Technologies, Inc. | Dry powder treprostinil for the treatment of pulmonary hypertension |
| US11712442B2 (en) | 2016-05-05 | 2023-08-01 | Liquidia Technologies, Inc. | Dry powder treprostinil for the treatment of pulmonary hypertension |
| US11744835B2 (en) | 2016-05-05 | 2023-09-05 | Liquidia Technologies, Inc. | Dry powder treprostinil for the treatment of pulmonary hypertension |
| US11744836B2 (en) | 2016-05-05 | 2023-09-05 | Liquidia Technologies, Inc. | Dry powder treprostinil for the treatment of pulmonary hypertension |
| US12390475B2 (en) | 2016-05-05 | 2025-08-19 | Liquidia Technologies, Inc. | Dry powder treprostinil for the treatment of pulmonary hypertension |
Also Published As
| Publication number | Publication date |
|---|---|
| US20030053958A1 (en) | 2003-03-20 |
| EP1161234A2 (en) | 2001-12-12 |
| WO2000054758A3 (en) | 2001-02-08 |
| CA2365890C (en) | 2010-09-21 |
| DE60004181T2 (de) | 2004-04-15 |
| CN1196479C (zh) | 2005-04-13 |
| KR20010108352A (ko) | 2001-12-07 |
| EP1161234B1 (en) | 2003-07-30 |
| US6756033B2 (en) | 2004-06-29 |
| WO2000054758A2 (en) | 2000-09-21 |
| PT1161234E (pt) | 2003-12-31 |
| DE60004181D1 (de) | 2003-09-04 |
| ATE245979T1 (de) | 2003-08-15 |
| JP2002539154A (ja) | 2002-11-19 |
| ES2203449T3 (es) | 2004-04-16 |
| KR100750384B1 (ko) | 2007-08-17 |
| CA2365890A1 (en) | 2000-09-21 |
| JP2011201907A (ja) | 2011-10-13 |
| CN1379665A (zh) | 2002-11-13 |
| DK1161234T3 (da) | 2003-11-24 |
| AU4082700A (en) | 2000-10-04 |
| US6521212B1 (en) | 2003-02-18 |
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