CA2549724C - Use of treprostinil to treat and prevent ischemic lesions - Google Patents
Use of treprostinil to treat and prevent ischemic lesions Download PDFInfo
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- CA2549724C CA2549724C CA2549724A CA2549724A CA2549724C CA 2549724 C CA2549724 C CA 2549724C CA 2549724 A CA2549724 A CA 2549724A CA 2549724 A CA2549724 A CA 2549724A CA 2549724 C CA2549724 C CA 2549724C
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- treprostinil
- ischemic lesions
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Landscapes
- Health & Medical Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52962203P | 2003-12-16 | 2003-12-16 | |
| US60/529,622 | 2003-12-16 | ||
| PCT/US2004/042283 WO2005058303A1 (en) | 2003-12-16 | 2004-12-16 | Use of treprostinil to treat and prevent ischemic lesions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2549724A1 CA2549724A1 (en) | 2005-06-30 |
| CA2549724C true CA2549724C (en) | 2014-02-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2549724A Expired - Fee Related CA2549724C (en) | 2003-12-16 | 2004-12-16 | Use of treprostinil to treat and prevent ischemic lesions |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8765813B2 (https=) |
| EP (1) | EP1696900B1 (https=) |
| JP (2) | JP5190200B2 (https=) |
| KR (1) | KR101161889B1 (https=) |
| CN (2) | CN1917866B (https=) |
| AT (1) | ATE473736T1 (https=) |
| CA (1) | CA2549724C (https=) |
| DE (1) | DE602004028155D1 (https=) |
| ES (1) | ES2347254T3 (https=) |
| WO (1) | WO2005058303A1 (https=) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101265226B (zh) | 2003-05-22 | 2013-04-24 | 联合治疗公司 | 化合物和释放前列环素类似物的方法 |
| CA2549801C (en) * | 2003-12-16 | 2012-10-16 | United Therapeutics Corporation | Use of treprostinil to improve kidney functions |
| CN1917866B (zh) * | 2003-12-16 | 2010-12-15 | 联合治疗公司 | 曲前列环素或它的衍生物，或其药学上可接受的盐在制备治疗和预防缺血性损害的药物中的用途 |
| ATE462427T1 (de) | 2004-04-12 | 2010-04-15 | United Therapeutics Corp | Verwendung von treprostinil zur behandlung von neuropathischen diabetischen fussgeschwüren |
| US8747897B2 (en) * | 2006-04-27 | 2014-06-10 | Supernus Pharmaceuticals, Inc. | Osmotic drug delivery system |
| CN101495122B (zh) | 2006-05-15 | 2011-10-05 | 联合治疗公司 | 使用定量吸入器给予曲前列尼 |
| DE102006026786A1 (de) | 2006-06-07 | 2007-12-13 | Joachim Kern | Dosierinhalator |
| KR20160048222A (ko) | 2007-12-17 | 2016-05-03 | 유나이티드 세러퓨틱스 코오포레이션 | 레모둘린?의 활성 성분인 트레프로스티닐의 개선된 제조 방법 |
| US8350079B2 (en) * | 2008-05-08 | 2013-01-08 | United Therapeutics Corporation | Treprostinil formulation |
| JP5649645B2 (ja) * | 2009-05-07 | 2015-01-07 | ユナイテッド セラピューティクス コーポレイション | プロスタサイクリンアナログの固形製剤 |
| EP3108888B1 (en) | 2010-03-15 | 2020-02-12 | United Therapeutics Corporation | Treatment for pulmonary hypertension |
| WO2011153363A1 (en) | 2010-06-03 | 2011-12-08 | United Therapeutics Corporation | Treprostinil production |
| WO2011159693A2 (en) * | 2010-06-15 | 2011-12-22 | United Therapeutics Corporation | Oral treatment of digital ischemic lesions |
| EP2681204B1 (en) | 2011-03-02 | 2016-04-27 | United Therapeutics Corporation | Synthesis of intermediate for treprostinil production |
| 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 |
| 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 |
| CA2880808C (en) * | 2012-08-01 | 2023-01-24 | United Therapeutics Corporation | Treatment of pulmonary arterial hypertension with mesenchymal stem cells |
| ES2869701T3 (es) | 2012-08-01 | 2021-10-25 | United Therapeutics Corp | Tratamiento de hipertensión arterial pulmonar con células progenitoras endoteliales tratadas con prostaciclina |
| JP6431850B2 (ja) | 2013-01-09 | 2018-11-28 | ユナイテッド セラピューティクス コーポレイション | プロスタサイクリンおよび間葉系幹細胞による脈管障害の処置 |
| EP3712142B1 (en) | 2013-01-11 | 2022-07-06 | Corsair Pharma, Inc. | Prodrugs of treprostinil |
| US9505737B2 (en) | 2013-01-11 | 2016-11-29 | Corsair Pharma, Inc. | Treprostinil derivative compounds and methods of using same |
| EP2970091A4 (en) | 2013-03-14 | 2017-02-08 | United Therapeutics Corporation | Solid forms of treprostinil |
| US20140275616A1 (en) | 2013-03-15 | 2014-09-18 | United Therapeutics Corporation | Salts of treprostinil |
| EP2978313B1 (en) | 2013-03-25 | 2018-02-21 | United Therapeutics Corporation | Process of making prostacyclin compounds with linker thiol and pegylated forms |
| FR3008320B1 (fr) * | 2013-07-15 | 2018-04-20 | Centre Hospitalier Univ Grenoble | Dispositif de prevention ou de traitement d'une ulceration cutanee |
| CA3042642A1 (en) | 2013-08-12 | 2015-02-19 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded immediate release abuse deterrent pill |
| LT3060041T (lt) | 2013-10-25 | 2021-03-25 | Insmed Incorporated | Prostaciklino junginiai |
| US9492444B2 (en) | 2013-12-17 | 2016-11-15 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| US10172797B2 (en) | 2013-12-17 | 2019-01-08 | Pharmaceutical Manufacturing Research Services, Inc. | Extruded extended release abuse deterrent pill |
| CN106573066A (zh) | 2014-06-13 | 2017-04-19 | 联合治疗学有限公司 | 曲前列环素制剂 |
| CA2955229C (en) | 2014-07-17 | 2020-03-10 | Pharmaceutical Manufacturing Research Services, Inc. | Immediate release abuse deterrent liquid fill dosage form |
| ES2778274T3 (es) | 2014-10-20 | 2020-08-10 | United Therapeutics Corp | Síntesis de productos intermedios para producir derivados de prostaciclina |
| WO2016064873A1 (en) | 2014-10-20 | 2016-04-28 | Pharmaceutical Manufacturing Research Services, Inc. | Extended release abuse deterrent liquid fill dosage form |
| JP6866043B2 (ja) | 2014-11-18 | 2021-04-28 | インスメッド インコーポレイテッド | トレプロスチニルプロドラッグおよびトレプロスチニル誘導体プロドラッグの製造方法 |
| IL252577B (en) | 2014-12-03 | 2022-07-01 | Steadymed Ltd | Preservative-free treprostinil formulations and methods and devices for use with same |
| US9394227B1 (en) | 2015-06-17 | 2016-07-19 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
| US9643911B2 (en) | 2015-06-17 | 2017-05-09 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
| JO3749B1 (ar) * | 2015-08-27 | 2021-01-31 | Lilly Co Eli | تركيبات إنسولين سريعة المفعول |
| US10898494B2 (en) | 2016-05-05 | 2021-01-26 | Liquidia Technologies, 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 |
| ES2927406T3 (es) | 2016-10-24 | 2022-11-04 | United Therapeutics Corp | Potenciación de las propiedades inmunomoduladoras de las MSC mediante treprostinil |
| US20190290597A1 (en) * | 2016-12-05 | 2019-09-26 | Corsair Pharma, Inc. | Dermal and transdermal administration of treprostinil and salts thereof |
| US10799653B2 (en) | 2017-01-09 | 2020-10-13 | United Therapeutics Corporation | Aerosol delivery device and method for manufacturing and operating the same |
| AU2019344541B2 (en) | 2018-09-18 | 2022-01-06 | Eli Lilly And Company | Erbumine salt of treprostinil |
| JP7455144B2 (ja) | 2019-04-29 | 2024-03-25 | インスメッド インコーポレイテッド | トレプロスチニルプロドラッグの乾燥粉末組成物およびその使用方法 |
| 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 |
| AU2021255621A1 (en) | 2020-04-17 | 2022-10-20 | United Therapeutics Corporation | Treprostinil for use in the treatment of intersitial lung disease |
| JP7608480B2 (ja) | 2020-06-09 | 2025-01-06 | 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フマリルジケトピペリジンプロドラッグ |
| WO2022132655A1 (en) | 2020-12-14 | 2022-06-23 | United Therapeutics Corporation | Methods of treating disease with treprostinil prodrugs |
| AU2022229367A1 (en) | 2021-03-03 | 2023-09-14 | 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) |
| US20230263807A1 (en) | 2022-02-08 | 2023-08-24 | United Therapeutics Corporation | Treprostinil iloprost combination therapy |
| KR20250002687A (ko) | 2022-04-29 | 2025-01-07 | 자오커 파마슈티컬 (광저우) 컴퍼니., 리미티드 | 트레프로스티닐 소프트 미스트 흡입제 |
| JP2026503509A (ja) | 2023-01-18 | 2026-01-29 | ユナイテッド セラピューティクス コーポレイション | 肺動脈性肺高血圧症の治療 |
| AU2024208919A1 (en) | 2023-01-19 | 2025-07-17 | United Therapeutics Corporation | Treprostinil analogs |
| US20250049743A1 (en) | 2023-08-08 | 2025-02-13 | United Therapeutics Corporation | Method of producing an oral osmotic pharmaceutical delivery system and a pharmaceutical batch produced using the same |
| US20250197338A1 (en) | 2023-11-09 | 2025-06-19 | United Therapeutics Corporation | Syntheses of compounds useful for producing treprostinil |
| WO2026035705A1 (en) | 2024-08-06 | 2026-02-12 | United Therapeutics Corporation | Treating pulmonary hypertension based on novel biomarker |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4254145A (en) * | 1978-08-16 | 1981-03-03 | American Cyanamid Company | Topical application of prostaglandin hypotensive agents |
| DE2845770A1 (de) * | 1978-10-19 | 1980-04-30 | Schering Ag | Neue prostacyclin-derivate und verfahren zu ihrer herstellung |
| US4281113A (en) * | 1979-07-31 | 1981-07-28 | The Upjohn Company | 2,5-Inter-o-phenylene-3,4-dinor-6,9α-epoxy-6.beta.-5-iodo-PGF1 compounds |
| CA1201712A (en) | 1980-02-28 | 1986-03-11 | Paul A. Aristoff | Carbacyclin analogs |
| 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 |
| DE3048906A1 (de) * | 1980-12-19 | 1982-07-15 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue carbacycline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| US4349689A (en) * | 1980-12-22 | 1982-09-14 | The Upjohn Company | Methano carbacyclin analogs |
| US4486598A (en) * | 1982-02-22 | 1984-12-04 | The Upjohn Company | Carbacyclin analogs |
| ZA851337B (en) | 1984-03-08 | 1985-10-30 | Upjohn Co | Interphenylene carbacyclin derivatives |
| US4668814A (en) * | 1984-03-08 | 1987-05-26 | The Upjohn Company | Interphenylene carbacyclin derivatives |
| US4683330A (en) * | 1984-03-08 | 1987-07-28 | The Upjohn Company | Interphenylene carbacyclin derivatives |
| CA1241324A (en) | 1984-03-08 | 1988-08-30 | Paul A. Aristoff | Interphenylene carbacyclin derivatives |
| DE3686025T2 (de) * | 1985-05-22 | 1993-01-07 | Liposome Technology Inc | Verfahren und system zum einatmen von liposomen. |
| 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 |
| GB9011588D0 (en) | 1990-05-24 | 1990-07-11 | Wellcome Found | Prostaglandin analogues 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 |
| AU735975B2 (en) | 1995-02-27 | 2001-07-19 | Toray Industries, Inc. | Remedy for pulmonary heart |
| US6441245B1 (en) * | 1997-10-24 | 2002-08-27 | United Therapeutics Corporation | Process for stereoselective synthesis of prostacyclin derivatives |
| EP1045695B1 (en) * | 1997-11-14 | 2004-03-24 | 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 f 1? 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 |
| CN1354622A (zh) | 1999-03-31 | 2002-06-19 | 联合治疗公司 | 前列腺素类化合物、组合物和治疗外周血管疾病和肺动脉高压的方法 |
| JP2003501092A (ja) * | 1999-06-07 | 2003-01-14 | エドワーズ ライフサイエンシーズ コーポレイション | 標的化新脈管形成 |
| AU2002339730A1 (en) * | 2002-08-28 | 2004-03-19 | Universita "Campus Bio-Medico" Di Roma | Use of prostacyclin and analogs thereof for improving venous flow |
| US7550133B2 (en) * | 2002-11-26 | 2009-06-23 | Alexza Pharmaceuticals, Inc. | Respiratory drug condensation aerosols and methods of making and using them |
| CN101265226B (zh) * | 2003-05-22 | 2013-04-24 | 联合治疗公司 | 化合物和释放前列环素类似物的方法 |
| US20040265238A1 (en) * | 2003-06-27 | 2004-12-30 | Imtiaz Chaudry | Inhalable formulations for treating pulmonary hypertension and methods of using same |
| CN1917866B (zh) * | 2003-12-16 | 2010-12-15 | 联合治疗公司 | 曲前列环素或它的衍生物，或其药学上可接受的盐在制备治疗和预防缺血性损害的药物中的用途 |
| ATE462427T1 (de) * | 2004-04-12 | 2010-04-15 | United Therapeutics Corp | Verwendung von treprostinil zur behandlung von neuropathischen diabetischen fussgeschwüren |
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- 2004-12-16 KR KR1020067013988A patent/KR101161889B1/ko not_active Expired - Fee Related
- 2004-12-16 WO PCT/US2004/042283 patent/WO2005058303A1/en not_active Ceased
- 2004-12-16 CN CN2009101645686A patent/CN101647792B/zh not_active Expired - Fee Related
- 2004-12-16 AT AT04814462T patent/ATE473736T1/de not_active IP Right Cessation
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- 2004-12-16 US US11/012,723 patent/US8765813B2/en active Active
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2012
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| JP5190200B2 (ja) | 2013-04-24 |
| EP1696900B1 (en) | 2010-07-14 |
| WO2005058303A1 (en) | 2005-06-30 |
| CN101647792A (zh) | 2010-02-17 |
| CN101647792B (zh) | 2012-11-28 |
| CA2549724A1 (en) | 2005-06-30 |
| US20050165111A1 (en) | 2005-07-28 |
| CN1917866B (zh) | 2010-12-15 |
| DE602004028155D1 (de) | 2010-08-26 |
| EP1696900A1 (en) | 2006-09-06 |
| KR20060123483A (ko) | 2006-12-01 |
| ATE473736T1 (de) | 2010-07-15 |
| CN1917866A (zh) | 2007-02-21 |
| JP2007514750A (ja) | 2007-06-07 |
| KR101161889B1 (ko) | 2012-07-02 |
| JP2013047235A (ja) | 2013-03-07 |
| US8765813B2 (en) | 2014-07-01 |
| ES2347254T3 (es) | 2010-10-27 |
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