WO2010129757A1 - Solid formulations of prostacyclin analogs - Google Patents
Solid formulations of prostacyclin analogs Download PDFInfo
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- WO2010129757A1 WO2010129757A1 PCT/US2010/033852 US2010033852W WO2010129757A1 WO 2010129757 A1 WO2010129757 A1 WO 2010129757A1 US 2010033852 W US2010033852 W US 2010033852W WO 2010129757 A1 WO2010129757 A1 WO 2010129757A1
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- treprostinil
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- 229910000280 sodium bentonite Inorganic materials 0.000 description 1
- 229940080314 sodium bentonite Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Classifications
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/03—Containers specially adapted for medical or pharmaceutical purposes for pills or tablets
-
- 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
-
- 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
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201080019951.3A CN102421288B (en) | 2009-05-07 | 2010-05-06 | Solid formulations of prostacyclin analogs |
JP2012509968A JP5649645B2 (en) | 2009-05-07 | 2010-05-06 | Prostacyclin analog solid formulation |
CA2760499A CA2760499C (en) | 2009-05-07 | 2010-05-06 | Solid formulations of prostacyclin analogs |
EP10772819.8A EP2427054A4 (en) | 2009-05-07 | 2010-05-06 | Solid formulations of prostacyclin analogs |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17626809P | 2009-05-07 | 2009-05-07 | |
US61/176,268 | 2009-05-07 |
Publications (1)
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WO2010129757A1 true WO2010129757A1 (en) | 2010-11-11 |
Family
ID=43050464
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2010/033852 WO2010129757A1 (en) | 2009-05-07 | 2010-05-06 | Solid formulations of prostacyclin analogs |
Country Status (7)
Country | Link |
---|---|
US (1) | US8349892B2 (en) |
EP (1) | EP2427054A4 (en) |
JP (1) | JP5649645B2 (en) |
KR (1) | KR101544246B1 (en) |
CN (1) | CN102421288B (en) |
CA (1) | CA2760499C (en) |
WO (1) | WO2010129757A1 (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
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EP2582235A2 (en) * | 2010-06-15 | 2013-04-24 | United Therapeutics Corporation | Oral treatment of digital ischemic lesions |
WO2013104318A1 (en) * | 2012-01-10 | 2013-07-18 | 上海天伟生物制药有限公司 | Crystal form of prostaglandin analogue, and preparation method and use thereof |
US9371264B2 (en) | 2013-01-11 | 2016-06-21 | Corsair Pharma, Inc. | Treprostinil derivative compounds and methods of using same |
US9394227B1 (en) | 2015-06-17 | 2016-07-19 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
US9469600B2 (en) | 2013-10-25 | 2016-10-18 | Insmed Incorporated | Prostacyclin compounds, compositions and methods of use thereof |
US9505737B2 (en) | 2013-01-11 | 2016-11-29 | Corsair Pharma, Inc. | Treprostinil derivative compounds and methods of using same |
US9643911B2 (en) | 2015-06-17 | 2017-05-09 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
US10343979B2 (en) | 2014-11-18 | 2019-07-09 | Insmed Incorporated | Methods of manufacturing treprostinil and treprostinil derivative prodrugs |
US11458098B2 (en) | 2019-04-29 | 2022-10-04 | Insmed Incorporated | Dry powder compositions of treprostinil prodrugs and methods of use thereof |
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Publication number | Priority date | Publication date | Assignee | Title |
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EP1628654B2 (en) | 2003-05-22 | 2019-12-04 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
US7879909B2 (en) * | 2004-04-12 | 2011-02-01 | United Therapeutics Corporation | Use of Treprostinil to treat neuropathic diabetic foot ulcers |
KR101390579B1 (en) | 2006-05-15 | 2014-05-19 | 유나이티드 세러퓨틱스 코오포레이션 | Treprostinil administration using a metered dose inhaler |
DE102006026786A1 (en) | 2006-06-07 | 2007-12-13 | Joachim Kern | metered dose inhaler |
EP2252570B1 (en) | 2007-12-17 | 2017-04-05 | United Therapeutics Corporation | An improved process to prepare treprostinil, the active ingredient in remodulin ® |
ES2611187T3 (en) | 2010-03-15 | 2017-05-05 | United Therapeutics Corporation | Treatment for pulmonary hypertension |
JP6046034B2 (en) | 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 | Production of treprostinil |
US8461393B2 (en) | 2011-03-02 | 2013-06-11 | United Therapeutics Corporation | Synthesis of intermediate for treprostinil production |
CA3125504C (en) | 2013-03-14 | 2023-10-24 | 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 |
CN106573066A (en) | 2014-06-13 | 2017-04-19 | 联合治疗学有限公司 | Treprostinil formulations |
EP3209415B1 (en) | 2014-10-20 | 2020-02-19 | United Therapeutics Corporation | Synthesis of intermediates for producing prostacyclin derivatives |
WO2018058124A1 (en) | 2016-09-26 | 2018-03-29 | United Therapeutics Corporation | Treprostinil prodrugs |
US10799653B2 (en) | 2017-01-09 | 2020-10-13 | United Therapeutics Corporation | Aerosol delivery device and method for manufacturing and operating the same |
JP2022546314A (en) | 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 | Treprostinil prodrug |
JP2023523557A (en) | 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 | Treprostinil for use in the treatment of interstitial lung disease |
US11793780B2 (en) | 2020-06-09 | 2023-10-24 | United Therapeutics Corporation | Prodrugs of treprosiinil |
KR20230134480A (en) | 2020-12-14 | 2023-09-21 | 유나이티드 쎄러퓨틱스 코포레이션 | How to Treat Disease with Treprostinil Prodrugs |
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) |
US20230263807A1 (en) | 2022-02-08 | 2023-08-24 | United Therapeutics Corporation | Treprostinil iloprost combination therapy |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050085540A1 (en) * | 2003-05-22 | 2005-04-21 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
US20060194842A1 (en) * | 2005-02-22 | 2006-08-31 | Chikara Uchida | Oxyindole derivatives |
US20060222792A1 (en) * | 2006-04-21 | 2006-10-05 | Chemagis Ltd. | Temozolomide storage system |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4306075A (en) * | 1980-03-28 | 1981-12-15 | The Upjohn Company | Composition and process |
GB8814438D0 (en) * | 1988-06-17 | 1988-07-20 | Wellcome Found | Compounds for use in medicine |
GB9011588D0 (en) * | 1990-05-24 | 1990-07-11 | Wellcome Found | Prostaglandin analogues for use in medicine |
US6441245B1 (en) * | 1997-10-24 | 2002-08-27 | United Therapeutics Corporation | Process for stereoselective synthesis of prostacyclin derivatives |
KR100638684B1 (en) * | 1997-11-14 | 2006-10-27 | 유나이티드 세러퓨틱스 코오포레이션 | 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 |
US6700025B2 (en) * | 2001-01-05 | 2004-03-02 | United Therapeutics Corporation | Process for stereoselective synthesis of prostacyclin derivatives |
US6803386B2 (en) * | 2002-01-16 | 2004-10-12 | United Therapeutics Corporation | Prostacyclin derivative containing compositions and methods of using the same for the treatment of cancer |
JPWO2003064369A1 (en) * | 2002-01-30 | 2005-05-26 | キッセイ薬品工業株式会社 | Novel thyroid hormone receptor ligands, pharmaceutical compositions containing them, and uses thereof |
US20040265238A1 (en) * | 2003-06-27 | 2004-12-30 | Imtiaz Chaudry | Inhalable formulations for treating pulmonary hypertension and methods of using same |
US20050101608A1 (en) * | 2003-09-24 | 2005-05-12 | Santel Donald J. | Iloprost in combination therapies for the treatment of pulmonary arterial hypertension |
CN101647792B (en) * | 2003-12-16 | 2012-11-28 | 联合治疗公司 | Use of treprostinil to treat and prevent ischemic lesions |
CN1917883B (en) * | 2003-12-16 | 2011-05-11 | 联合治疗公司 | Use of treprostinil in preparing medicine to improve kidney functions |
US7879909B2 (en) * | 2004-04-12 | 2011-02-01 | United Therapeutics Corporation | Use of Treprostinil to treat neuropathic diabetic foot ulcers |
US8747897B2 (en) * | 2006-04-27 | 2014-06-10 | Supernus Pharmaceuticals, Inc. | Osmotic drug delivery system |
KR101390579B1 (en) * | 2006-05-15 | 2014-05-19 | 유나이티드 세러퓨틱스 코오포레이션 | Treprostinil administration using a metered dose inhaler |
US20090281129A1 (en) * | 2006-05-15 | 2009-11-12 | Senex Biotechnology, Inc. | Cdki pathway inhibitors and uses thereof |
AU2007338701A1 (en) | 2006-12-21 | 2008-07-03 | Concert Pharmaceuticals Inc. | Prostacyclin derivatives |
CA2678258A1 (en) * | 2007-02-09 | 2008-08-14 | United Therapeutics Corporation | Treprostinil treatment for interstitial lung disease and asthma |
CA2677989C (en) * | 2007-02-20 | 2018-04-24 | Eurand Pharmaceuticals Limited | Stable digestive enzyme compositions |
EP2252570B1 (en) * | 2007-12-17 | 2017-04-05 | United Therapeutics Corporation | An improved process to prepare treprostinil, the active ingredient in remodulin ® |
-
2010
- 2010-05-06 WO PCT/US2010/033852 patent/WO2010129757A1/en active Application Filing
- 2010-05-06 JP JP2012509968A patent/JP5649645B2/en active Active
- 2010-05-06 KR KR1020117028834A patent/KR101544246B1/en active IP Right Grant
- 2010-05-06 CA CA2760499A patent/CA2760499C/en active Active
- 2010-05-06 US US12/775,102 patent/US8349892B2/en active Active
- 2010-05-06 CN CN201080019951.3A patent/CN102421288B/en active Active
- 2010-05-06 EP EP10772819.8A patent/EP2427054A4/en not_active Withdrawn
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050085540A1 (en) * | 2003-05-22 | 2005-04-21 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
US20070082948A1 (en) * | 2003-05-22 | 2007-04-12 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
US20080249167A1 (en) * | 2003-05-22 | 2008-10-09 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
US20060194842A1 (en) * | 2005-02-22 | 2006-08-31 | Chikara Uchida | Oxyindole derivatives |
US20060222792A1 (en) * | 2006-04-21 | 2006-10-05 | Chemagis Ltd. | Temozolomide storage system |
Non-Patent Citations (1)
Title |
---|
See also references of EP2427054A4 * |
Cited By (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2582235A2 (en) * | 2010-06-15 | 2013-04-24 | United Therapeutics Corporation | Oral treatment of digital ischemic lesions |
EP2582235A4 (en) * | 2010-06-15 | 2014-04-30 | United Therapeutics Corp | Oral treatment of digital ischemic lesions |
WO2013104318A1 (en) * | 2012-01-10 | 2013-07-18 | 上海天伟生物制药有限公司 | Crystal form of prostaglandin analogue, and preparation method and use thereof |
US9278903B2 (en) | 2012-01-10 | 2016-03-08 | Shanghai Techwell Biopharmaceutical Co., Ltd. | Crystal form of prostaglandin analogue, and preparation method and use thereof |
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Also Published As
Publication number | Publication date |
---|---|
CN102421288B (en) | 2015-04-22 |
US8349892B2 (en) | 2013-01-08 |
JP5649645B2 (en) | 2015-01-07 |
US20100282622A1 (en) | 2010-11-11 |
EP2427054A1 (en) | 2012-03-14 |
CN102421288A (en) | 2012-04-18 |
JP2012526140A (en) | 2012-10-25 |
EP2427054A4 (en) | 2014-01-15 |
KR101544246B1 (en) | 2015-08-12 |
CA2760499C (en) | 2015-11-03 |
CA2760499A1 (en) | 2010-11-11 |
KR20120017058A (en) | 2012-02-27 |
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