DE60004181T2 - Behandlung der pulmonalen hypertension durch inhalation von benzinden-prostaglandine - Google Patents
Behandlung der pulmonalen hypertension durch inhalation von benzinden-prostaglandine Download PDFInfo
- Publication number
- DE60004181T2 DE60004181T2 DE60004181T DE60004181T DE60004181T2 DE 60004181 T2 DE60004181 T2 DE 60004181T2 DE 60004181 T DE60004181 T DE 60004181T DE 60004181 T DE60004181 T DE 60004181T DE 60004181 T2 DE60004181 T2 DE 60004181T2
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- Prior art keywords
- baseline
- aerosolized
- pulmonary
- intravenous
- aerosol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/19—Carboxylic acids, e.g. valproic acid
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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
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- 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)
- Dispersion Chemistry (AREA)
- Otolaryngology (AREA)
- Cardiology (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 | |
| US124999P | 1999-03-18 | ||
| PCT/US2000/040040 WO2000054758A2 (en) | 1999-03-18 | 2000-03-17 | Method for delivering benzidine prostaglandins by inhalation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60004181D1 DE60004181D1 (de) | 2003-09-04 |
| DE60004181T2 true DE60004181T2 (de) | 2004-04-15 |
Family
ID=22417774
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60004181T Expired - Lifetime DE60004181T2 (de) | 1999-03-18 | 2000-03-17 | Behandlung der pulmonalen hypertension durch inhalation von benzinden-prostaglandine |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6521212B1 (https=) |
| EP (1) | EP1161234B1 (https=) |
| JP (2) | JP4819224B2 (https=) |
| KR (1) | KR100750384B1 (https=) |
| CN (1) | CN1196479C (https=) |
| AT (1) | ATE245979T1 (https=) |
| AU (1) | AU4082700A (https=) |
| CA (1) | CA2365890C (https=) |
| DE (1) | DE60004181T2 (https=) |
| DK (1) | DK1161234T3 (https=) |
| ES (1) | ES2203449T3 (https=) |
| PT (1) | PT1161234E (https=) |
| WO (1) | WO2000054758A2 (https=) |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6521212B1 (en) * | 1999-03-18 | 2003-02-18 | United Therapeutics Corporation | Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation |
| DE10163697A1 (de) * | 2001-12-21 | 2003-07-03 | Studiengesellschaft Kohle Mbh | Reversible Speicherung von Wasserstoff mit Hilfe von dotierten Alkalimetallaluminiumhydriden |
| US7811606B2 (en) | 2003-04-16 | 2010-10-12 | Dey, L.P. | Nasal pharmaceutical formulations and methods of using the same |
| US9808471B2 (en) | 2003-04-16 | 2017-11-07 | Mylan Specialty Lp | Nasal pharmaceutical formulations and methods of using the same |
| US8912174B2 (en) | 2003-04-16 | 2014-12-16 | Mylan Pharmaceuticals Inc. | Formulations and methods for treating rhinosinusitis |
| ES2622471T5 (es) | 2003-05-22 | 2020-07-23 | United Therapeutics Corp | Compuestos y procedimientos para la administración de análogos de prostaciclina |
| 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 |
| US20090124697A1 (en) * | 2003-12-16 | 2009-05-14 | United Therapeutics Corporation | Inhalation formulations of treprostinil |
| DE602004028155D1 (de) * | 2003-12-16 | 2010-08-26 | United Therapeutics Corp | Verwendung von treprostinil zur behandlung von ischämischen läsionen |
| ATE441418T1 (de) * | 2003-12-16 | 2009-09-15 | United Therapeutics Corp | Verwendung von treprostinil zur verbesserung der nierenfunktion |
| WO2005099680A2 (en) * | 2004-04-12 | 2005-10-27 | United Therapeutics, Inc. | Use of treprostinil to treat neuropathic diabetic foot ulcers |
| JP2008523090A (ja) * | 2004-12-08 | 2008-07-03 | バイオマリン ファーマシューティカル インコーポレイテッド | 新生児肺高血圧症の治療のための方法および組成物 |
| WO2007067570A1 (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 |
| EP2026816B1 (en) * | 2006-05-15 | 2018-10-24 | United Therapeutics Corporation | Treprostinil administration using a metered dose inhaler |
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| US20090036465A1 (en) * | 2006-10-18 | 2009-02-05 | United Therapeutics Corporation | Combination therapy for pulmonary arterial hypertension |
| US20100009997A1 (en) * | 2007-01-12 | 2010-01-14 | Biomarin Pharmaceutical Inc. | Method of treating a metabolic or neuropsychiarty disorder with a bh4 derivative prodrug |
| JP2010518122A (ja) * | 2007-02-09 | 2010-05-27 | ユナイテッド セラピューティクス コーポレーション | 間質性肺疾患および喘息のためのトレプロスチニル処置 |
| CN101903324B (zh) | 2007-12-17 | 2013-07-03 | 联合治疗公司 | 一种制备Remodulin中的活性成分曲前列素的改良方法 |
| CA2723540C (en) * | 2008-05-08 | 2016-01-05 | United Therapeutics Corporation | Treprostinil monohydrate |
| CN102164487A (zh) * | 2008-09-25 | 2011-08-24 | 阿拉迪姆公司 | 曲前列素的深肺部递送 |
| US8349892B2 (en) * | 2009-05-07 | 2013-01-08 | United Therapeutics Corporation | Solid formulations of prostacyclin analogs |
| ES2611187T3 (es) | 2010-03-15 | 2017-05-05 | United Therapeutics Corporation | Tratamiento para hipertensión pulmonar |
| JP6046034B2 (ja) | 2010-06-03 | 2016-12-14 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニルの製造 |
| US20130345471A1 (en) | 2011-03-02 | 2013-12-26 | United Therapeutics Corporation | Synthesis of intermediate for treprostinil production |
| CN103193627B (zh) | 2012-01-10 | 2016-04-20 | 上海天伟生物制药有限公司 | 一种前列腺素类似物的晶型及其制备方法和用途 |
| CN103193626B (zh) | 2012-01-10 | 2016-05-11 | 上海天伟生物制药有限公司 | 一种前列腺素类似物的晶型及其制备方法和用途 |
| US9387214B2 (en) | 2012-01-13 | 2016-07-12 | United Therapeutics Corporation | Method of identifying therapies for pulmonary hypertension |
| AU2013351934B2 (en) * | 2012-11-30 | 2018-03-29 | Insmed Incorporated | Prostacylin compositions and methods for using the same |
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| CN109608326A (zh) | 2013-03-15 | 2019-04-12 | 联合治疗公司 | 曲前列环素的盐 |
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| ES2860975T3 (es) | 2013-10-25 | 2021-10-05 | Insmed Inc | Compuestos de prostaciclina |
| ES2908142T3 (es) | 2014-06-13 | 2022-04-27 | United Therapeutics Corp | Formulaciones de treprostinil |
| US9593061B2 (en) | 2014-10-20 | 2017-03-14 | United Therapeutics Corporation | Synthesis of intermediates for producing prostacyclin derivatives |
| AU2015349969B2 (en) | 2014-11-18 | 2020-02-06 | Insmed Incorporated | Methods of manufacturing treprostinil and treprostinil derivative prodrugs |
| CA2967899C (en) * | 2014-12-03 | 2023-09-19 | Steadymed Ltd | Preservative-free treprostinil formulations and methods and devices for use with same |
| RU2593016C2 (ru) * | 2014-12-15 | 2016-07-27 | Федеральное государственное бюджетное учреждение науки Институт теоретической и прикладной механики им. С.А. Христиановича Сибирского отделения Российской академии наук (ИТПМ СО РАН) | Способ лечения артериальной гипертензии путем ингаляционного введения аэрозоля гипотензивного препарата |
| IL262720B2 (en) | 2016-05-05 | 2024-06-01 | Liquidia Tech Inc | Dry powder treprostinil for the treatment of pulmonary hypertension |
| JP7220650B2 (ja) | 2016-09-26 | 2023-02-10 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニルプロドラッグ |
| MX2019006938A (es) | 2016-12-14 | 2019-09-06 | Respira Therapeutics Inc | Metodos y composiciones para trataminto de hipertension pulmonar y otros trastornos del pulmon. |
| US10799653B2 (en) | 2017-01-09 | 2020-10-13 | United Therapeutics Corporation | Aerosol delivery device and method for manufacturing and operating the same |
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| EP3498283A1 (en) | 2017-12-14 | 2019-06-19 | Ipsol AG | Glycosidic derivatives of treprostinil |
| ES2976468T3 (es) | 2018-09-18 | 2024-08-01 | Lilly Co Eli | Sal de treprostinil erbumina |
| MX2021003866A (es) | 2018-10-05 | 2021-09-08 | Xenotherapeutics Inc | Productos y metodos de xenotransplante. |
| US10883084B2 (en) | 2018-10-05 | 2021-01-05 | Xenotherapeutics, Inc. | Personalized cells, tissues, and organs for transplantation from a humanized, bespoke, designated-pathogen free, (non-human) donor and methods and products relating to same |
| CN114072136B (zh) | 2019-04-29 | 2024-11-29 | 英斯梅德股份有限公司 | 曲前列素前药的干粉组合物及其使用方法 |
| EP3750528A1 (en) | 2019-06-11 | 2020-12-16 | Nexien Biopharma, Inc. | Compositions for treating dystrophies and myotonia |
| EP4017588A1 (en) | 2019-08-23 | 2022-06-29 | United Therapeutics Corporation | Treprostinil prodrugs |
| US11339110B2 (en) | 2019-12-19 | 2022-05-24 | Chirogate International Inc. | Efficient crystallization process for preparing ultrapure Treprostinil and crystal prepared therefrom |
| JP2023523557A (ja) | 2020-04-17 | 2023-06-06 | ユナイテッド セラピューティクス コーポレイション | 間質性肺疾患の治療における使用のためのトレプロスチニル |
| IL298591A (en) | 2020-06-09 | 2023-01-01 | United Therapeutics Corp | Pomeryl dictopiperidine prodrugs of treprostinil |
| US11447440B2 (en) | 2020-10-29 | 2022-09-20 | Chirogate International Inc. | Treprostinil monohydrate crystals and methods for preparation thereof |
| KR20250133451A (ko) | 2020-12-14 | 2025-09-05 | 유나이티드 쎄러퓨틱스 코포레이션 | 트레프로스티닐 프로드러그로 질환을 치료하는 방법 |
| JP2024510930A (ja) | 2021-03-03 | 2024-03-12 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニル及びそのプロドラッグの乾燥粉末組成物、及び、さらに（ｅ）－３，６－ビス［４－（ｎ－カルボニル－２－プロペニル）アミドブチル］－２，５－ジケトピペラジン（ｆｄｋｐ）を含む乾燥粉末組成物 |
| WO2023154705A1 (en) | 2022-02-08 | 2023-08-17 | United Therapeutics Corporation | Treprostinil iloprost combination therapy |
| EP4516297A4 (en) | 2022-04-29 | 2026-02-25 | Zhaoke pharmaceutical guangzhou co ltd | Treprostinil Gentle Inhalation Mist |
| IL322117A (en) | 2023-01-18 | 2025-09-01 | United Therapeutics Corp | Treatment of pulmonary arterial hypertension |
| EP4652151A1 (en) | 2023-01-19 | 2025-11-26 | United Therapeutics Corporation | Treprostinil analogs |
| US20260041656A1 (en) | 2024-08-06 | 2026-02-12 | United Therapeutics Corporation | Treating pulmonary hypertension based on novel biomarker |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4338457A (en) * | 1980-02-28 | 1982-07-06 | The Upjohn Company | Composition and process |
| 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 |
| CA1241324A (en) | 1984-03-08 | 1988-08-30 | Paul A. Aristoff | Interphenylene carbacyclin derivatives |
| ZA851337B (en) * | 1984-03-08 | 1985-10-30 | Upjohn Co | Interphenylene carbacyclin derivatives |
| JPS63500175A (ja) * | 1985-05-22 | 1988-01-21 | リポソ−ム テクノロジ−，インコ−ポレイテツド | リポソ−ム吸入法および吸入システム |
| GB8814438D0 (en) | 1988-06-17 | 1988-07-20 | Wellcome Found | Compounds for use in medicine |
| KR0158870B1 (ko) * | 1988-06-17 | 1998-12-01 | 마틴 에이. 로쓰블랫 | 폐순환 승압의 치료, 예방 또는 진단용 조성물 |
| JP2704546B2 (ja) * | 1989-04-04 | 1998-01-26 | 光利 太良 | Ａｔｌｌ治療用吸入剤 |
| US5190972A (en) * | 1992-01-27 | 1993-03-02 | The University Of Melbourne | Method of combatting cyclosporine organ toxicity with prostaglandin analogs |
| CA2115065C (en) * | 1992-06-12 | 2000-10-03 | Kiyoyuki Sakon | Ultrafine particle powder for inhalation and method for production thereof |
| 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 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 DK DK00920253T patent/DK1161234T3/da active
- 2000-03-17 KR KR1020017011610A patent/KR100750384B1/ko not_active Expired - Lifetime
- 2000-03-17 AU AU40827/00A patent/AU4082700A/en not_active Abandoned
- 2000-03-17 WO PCT/US2000/040040 patent/WO2000054758A2/en not_active Ceased
- 2000-03-17 ES ES00920253T patent/ES2203449T3/es not_active Expired - Lifetime
- 2000-03-17 CA CA2365890A patent/CA2365890C/en not_active Expired - Lifetime
- 2000-03-17 DE DE60004181T patent/DE60004181T2/de not_active Expired - Lifetime
- 2000-03-17 JP JP2000604834A patent/JP4819224B2/ja not_active Expired - Lifetime
- 2000-03-17 EP EP00920253A patent/EP1161234B1/en 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
Also Published As
| Publication number | Publication date |
|---|---|
| CA2365890A1 (en) | 2000-09-21 |
| KR20010108352A (ko) | 2001-12-07 |
| CN1196479C (zh) | 2005-04-13 |
| CA2365890C (en) | 2010-09-21 |
| EP1161234A2 (en) | 2001-12-12 |
| DE60004181D1 (de) | 2003-09-04 |
| WO2000054758A2 (en) | 2000-09-21 |
| JP4819224B2 (ja) | 2011-11-24 |
| ES2203449T3 (es) | 2004-04-16 |
| AU4082700A (en) | 2000-10-04 |
| WO2000054758A3 (en) | 2001-02-08 |
| DK1161234T3 (da) | 2003-11-24 |
| ATE245979T1 (de) | 2003-08-15 |
| JP2002539154A (ja) | 2002-11-19 |
| KR100750384B1 (ko) | 2007-08-17 |
| PT1161234E (pt) | 2003-12-31 |
| US6756033B2 (en) | 2004-06-29 |
| JP2011201907A (ja) | 2011-10-13 |
| EP1161234B1 (en) | 2003-07-30 |
| US6521212B1 (en) | 2003-02-18 |
| CN1379665A (zh) | 2002-11-13 |
| US20030053958A1 (en) | 2003-03-20 |
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