ES2203449T3 - Tratamiento de la hipertension pulmonar por inhalacion de prostaglandinas de bencindeno. - Google Patents
Tratamiento de la hipertension pulmonar por inhalacion de prostaglandinas de bencindeno.Info
- Publication number
- ES2203449T3 ES2203449T3 ES00920253T ES00920253T ES2203449T3 ES 2203449 T3 ES2203449 T3 ES 2203449T3 ES 00920253 T ES00920253 T ES 00920253T ES 00920253 T ES00920253 T ES 00920253T ES 2203449 T3 ES2203449 T3 ES 2203449T3
- Authority
- ES
- Spain
- Prior art keywords
- pulmonary
- administration
- bencindene
- intravenously
- inhalation
- 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
Links
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- 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
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- 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
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- 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]
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- 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
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- 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)
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- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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Families Citing this family (62)
| 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 |
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| DE102006026786A1 (de) | 2006-06-07 | 2007-12-13 | Joachim Kern | Dosierinhalator |
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| WO2008089148A1 (en) * | 2007-01-12 | 2008-07-24 | Biomarin Pharmaceutical Inc. | Method of treating a metabolic or neuropsychiatry disorder with a bh4 derivative prodrug |
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| WO2010036798A1 (en) * | 2008-09-25 | 2010-04-01 | Aradigm Corporation | Deep lung pulmonary delivery of treprostinil |
| CN102421288B (zh) * | 2009-05-07 | 2015-04-22 | 联合治疗公司 | 前列环素类似物的固体剂型 |
| EP2547341B1 (en) | 2010-03-15 | 2016-09-14 | United Therapeutics Corporation | Treatment for pulmonary hypertension |
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| EP2681204B1 (en) | 2011-03-02 | 2016-04-27 | United Therapeutics Corporation | Synthesis of intermediate for treprostinil production |
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| EP3226838A1 (en) * | 2014-12-03 | 2017-10-11 | 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 |
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| EP3498283A1 (en) | 2017-12-14 | 2019-06-19 | Ipsol AG | Glycosidic derivatives of treprostinil |
| BR112021002200B1 (pt) | 2018-09-18 | 2024-03-12 | Eli Lilly And Company | Sal erbumina de trepostinila |
| AU2019356014A1 (en) | 2018-10-05 | 2021-05-20 | Alexis Bio, Inc. | Xenotransplantation products and methods |
| 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 |
| US11458098B2 (en) | 2019-04-29 | 2022-10-04 | Insmed Incorporated | Dry powder compositions of treprostinil prodrugs and methods of use thereof |
| EP3750528A1 (en) | 2019-06-11 | 2020-12-16 | Nexien Biopharma, Inc. | Compositions for treating dystrophies and myotonia |
| JP2022546314A (ja) | 2019-08-23 | 2022-11-04 | 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 |
| US11339110B2 (en) | 2019-12-19 | 2022-05-24 | Chirogate International Inc. | Efficient crystallization process for preparing ultrapure Treprostinil and crystal prepared therefrom |
| WO2021211916A1 (en) | 2020-04-17 | 2021-10-21 | United Therapeutics Corporation | Treprostinil for use in the treatment of intersitial lung disease |
| CN116113415A (zh) | 2020-06-09 | 2023-05-12 | 联合治疗公司 | 曲前列尼尔的富马酰基二酮哌啶前药 |
| US11447440B2 (en) | 2020-10-29 | 2022-09-20 | Chirogate International Inc. | Treprostinil monohydrate crystals and methods for preparation thereof |
| IL303668A (en) | 2020-12-14 | 2023-08-01 | United Therapeutics Corp | Stable treprostinil prodrugs and their uses for the treatment of diseases |
| EP4301372A1 (en) | 2021-03-03 | 2024-01-10 | United Therapeutics Corporation | A dry powder composition of trestinil and its prodrug thereof and further comprising comprising (e)-3,6-bis[4-(n-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine (fdkp) |
| EP4475819A1 (en) | 2022-02-08 | 2024-12-18 | United Therapeutics Corporation | Treprostinil iloprost combination therapy |
| EP4516297A1 (en) | 2022-04-29 | 2025-03-05 | Zhaoke Pharmaceutical (Guangzhou) Co., Ltd | Treprostinil soft mist inhalant |
| WO2024155751A1 (en) | 2023-01-18 | 2024-07-25 | United Therapeutics Corporation | Treatment of pulmonary arterial hypertension |
| EP4652151A1 (en) | 2023-01-19 | 2025-11-26 | United Therapeutics Corporation | Treprostinil analogs |
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 |
| ZA851337B (en) * | 1984-03-08 | 1985-10-30 | Upjohn Co | Interphenylene carbacyclin derivatives |
| CA1241324A (en) | 1984-03-08 | 1988-08-30 | Paul A. Aristoff | 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 |
| ES2045437T3 (es) * | 1988-06-17 | 1994-01-16 | Wellcome Found | Analogos de prostaglandinas para empleo en medicina. |
| GB8814438D0 (en) | 1988-06-17 | 1988-07-20 | Wellcome Found | Compounds for use in medicine |
| 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 |
| ATE222754T1 (de) * | 1992-06-12 | 2002-09-15 | Teijin Ltd | Ultrafeines pulver zur inhalation und dessen herstellung |
| AU1373499A (en) * | 1997-11-14 | 1999-06-07 | United Therapeutics Corporation | Use of 9-deoxy-2', 9-alpha-methano-3- oxa-4,5,6- trinor-3, 7-(1',3'-interphenylene) -13,14-dihydro- prostaglandin f1 to treat peripheral vascular disease |
| US6521212B1 (en) * | 1999-03-18 | 2003-02-18 | United Therapeutics Corporation | Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation |
-
2000
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- 2000-03-17 DE DE60004181T patent/DE60004181T2/de not_active Expired - Lifetime
- 2000-03-17 CN CNB008051089A patent/CN1196479C/zh not_active Expired - Lifetime
- 2000-03-17 PT PT00920253T patent/PT1161234E/pt unknown
- 2000-03-17 AU AU40827/00A patent/AU4082700A/en not_active Abandoned
- 2000-03-17 DK DK00920253T patent/DK1161234T3/da active
- 2000-03-17 ES ES00920253T patent/ES2203449T3/es not_active Expired - Lifetime
- 2000-03-17 WO PCT/US2000/040040 patent/WO2000054758A2/en not_active Ceased
- 2000-03-17 AT AT00920253T patent/ATE245979T1/de active
- 2000-03-17 JP JP2000604834A patent/JP4819224B2/ja not_active Expired - Lifetime
- 2000-03-17 EP EP00920253A patent/EP1161234B1/en not_active Expired - Lifetime
- 2000-03-17 KR KR1020017011610A patent/KR100750384B1/ko not_active Expired - Lifetime
- 2000-03-17 CA CA2365890A patent/CA2365890C/en not_active Expired - Lifetime
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2002
- 2002-08-06 US US10/212,149 patent/US6756033B2/en not_active Expired - Lifetime
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2011
- 2011-05-30 JP JP2011119894A patent/JP2011201907A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002539154A (ja) | 2002-11-19 |
| DE60004181D1 (de) | 2003-09-04 |
| WO2000054758A2 (en) | 2000-09-21 |
| CA2365890A1 (en) | 2000-09-21 |
| KR20010108352A (ko) | 2001-12-07 |
| ATE245979T1 (de) | 2003-08-15 |
| US6521212B1 (en) | 2003-02-18 |
| JP4819224B2 (ja) | 2011-11-24 |
| AU4082700A (en) | 2000-10-04 |
| US20030053958A1 (en) | 2003-03-20 |
| DE60004181T2 (de) | 2004-04-15 |
| CN1379665A (zh) | 2002-11-13 |
| WO2000054758A3 (en) | 2001-02-08 |
| US6756033B2 (en) | 2004-06-29 |
| JP2011201907A (ja) | 2011-10-13 |
| CN1196479C (zh) | 2005-04-13 |
| DK1161234T3 (da) | 2003-11-24 |
| PT1161234E (pt) | 2003-12-31 |
| KR100750384B1 (ko) | 2007-08-17 |
| EP1161234A2 (en) | 2001-12-12 |
| EP1161234B1 (en) | 2003-07-30 |
| CA2365890C (en) | 2010-09-21 |
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