CA2770403C - Intravenous formulations of neurokinin-1 antagonists - Google Patents
Intravenous formulations of neurokinin-1 antagonists Download PDFInfo
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- CA2770403C CA2770403C CA2770403A CA2770403A CA2770403C CA 2770403 C CA2770403 C CA 2770403C CA 2770403 A CA2770403 A CA 2770403A CA 2770403 A CA2770403 A CA 2770403A CA 2770403 C CA2770403 C CA 2770403C
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| Application Number | Priority Date | Filing Date | Title |
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| US23412909P | 2009-08-14 | 2009-08-14 | |
| US61/234,129 | 2009-08-14 | ||
| PCT/US2010/045317 WO2011019911A1 (en) | 2009-08-14 | 2010-08-12 | Intravenous formulations of neurokinin-1 antagonists |
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| CA2770403A1 CA2770403A1 (en) | 2011-02-17 |
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| CA2770403A Active CA2770403C (en) | 2009-08-14 | 2010-08-12 | Intravenous formulations of neurokinin-1 antagonists |
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| US7563801B2 (en) | 2006-04-05 | 2009-07-21 | Schering Corporation | Pharmaceutical formulations: salts of 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one and treatment methods using the same |
| AR066191A1 (es) | 2007-03-22 | 2009-08-05 | Schering Corp | Proceso e intermediarios para la sintesis de compuestos 8- [ ( 1- (3,5- bis- ( trifluorometil) fenil) - etoxi ) - metil]- 8 fenil - 1,7- diaza - espiro (4, 5) decan -2 ona |
| CA2736195C (en) | 2008-09-05 | 2017-05-16 | Opko Health, Inc. | Process and intermediates for the synthesis of 8-[{1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one compounds |
| MX336071B (es) | 2009-08-14 | 2016-01-06 | Opko Health Inc | Formulaciones intravenosas de antagonistas de neurocinina 1. |
| AR097683A1 (es) * | 2013-09-26 | 2016-04-06 | Lilly Co Eli | Compuestos y uso para la preparación de agentes de formación de imagen tau y formulaciones para la formación de imagen tau |
| JP6741655B2 (ja) | 2014-09-19 | 2020-08-19 | ヘロン セラピューティクス， インコーポレイテッドＨｅｒｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | アプレピタントのエマルジョン製剤 |
| DK3265087T3 (da) | 2015-03-04 | 2020-10-19 | Vanda Pharmaceuticals Inc | Fremgangsmåde til behandling med tradipitant |
| WO2017044693A1 (en) | 2015-09-11 | 2017-03-16 | Chase Pharmaceuticals Corporation | Muscarinic combination and its use for combating hypocholinergic disorders of the central nervous system |
| CA3013288A1 (en) * | 2016-02-01 | 2017-08-10 | Heron Therapeutics, Inc. | Emulsion comprising an nk-1 receptor antagonist |
| US9974742B2 (en) * | 2016-02-01 | 2018-05-22 | Heron Therapeutics, Inc. | Emulsion formulations of an NK-1 receptor antagonist and uses thereof |
| EP3493815B1 (en) * | 2016-08-03 | 2022-02-16 | Zhuhai Beihai Biotech Co., Ltd. | Formulations of fosaprepitant and aprepitant |
| CN109963583B (zh) * | 2016-11-21 | 2023-06-09 | 珠海贝海生物技术有限公司 | 罗拉吡坦制剂 |
| IL312486B2 (en) | 2017-04-10 | 2025-05-01 | Chase Therapeutics Corp | NK1 antagonist combination and method for treating synucleinopathies |
| WO2019005830A1 (en) | 2017-06-26 | 2019-01-03 | Fordoz Pharma Corp. | NANOSOME FORMULATIONS OF APREPITANT AND METHODS AND APPLICATIONS THEREOF |
| US11266633B2 (en) | 2017-06-30 | 2022-03-08 | Chase Therapeutics Corporation | NK-1 antagonist compositions and methods for use in treating depression |
| CN109200018A (zh) * | 2017-07-04 | 2019-01-15 | 南京诺瑞特医药科技有限公司 | 含有奈妥吡坦的微乳制剂 |
| CN108703950B (zh) * | 2018-08-27 | 2021-04-20 | 辅必成（上海）医药科技有限公司 | 一种罗拉吡坦的乳剂注射液 |
| CN109394693A (zh) * | 2018-12-25 | 2019-03-01 | 广州白云山汉方现代药业有限公司 | 一种罗拉匹坦乳剂及其制备方法和应用 |
| CN109453115A (zh) * | 2018-12-25 | 2019-03-12 | 广州白云山汉方现代药业有限公司 | 一种罗拉匹坦静脉注射乳剂及其制备方法和应用 |
| BR112021026554A2 (pt) | 2019-06-28 | 2022-05-24 | Jiangsu Hengrui Medicine Co | Antagonista de neurocinina-1 |
| KR20220165251A (ko) | 2020-04-03 | 2022-12-14 | 네르 쎄라퓨틱스 리미티드 | 패혈증, 패혈성 쇼크, 급성 호흡 곤란 증후군 (ards) 또는 다발성 기관 기능장애 증후군 (mods)으로부터 선택된 질환을 치료하기 위한 nk-1 수용체 길항제 |
| CA3177477A1 (en) | 2020-06-02 | 2021-12-09 | Nerre Therapeutics Limited | Neurokinin (nk)-1 receptor antagonists for use in the treatment of pulmonary fibrosis conditions promoted by mechanical injury to the lungs |
| KR20230127252A (ko) * | 2020-12-25 | 2023-08-31 | 상하이 쉥디 파마슈티컬 컴퍼니 리미티드 | 5-ht3 수용체 길항제와 조합된 nk1 길항제 전구약물화합물의 용도 |
| WO2023134725A1 (zh) * | 2022-01-12 | 2023-07-20 | 江苏恒瑞医药股份有限公司 | 一种包含神经激肽-1拮抗剂前药化合物的药物组合物 |
| WO2023134723A1 (zh) * | 2022-01-12 | 2023-07-20 | 江苏恒瑞医药股份有限公司 | 一种神经激肽-1拮抗剂前药化合物的晶型 |
| CN119528985A (zh) * | 2023-08-28 | 2025-02-28 | 科睿迪(南京)医药科技有限公司 | 神经激肽-1受体拮抗剂化合物 |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0338372A3 (en) * | 1988-04-22 | 1991-10-09 | American Cyanamid Company | Solubilized pro-drugs |
| JP3350048B2 (ja) * | 1989-07-07 | 2002-11-25 | アンドルシェルシュ・インコーポレイテッド | アンドロゲン関連疾患の治療方法 |
| US5610140A (en) * | 1991-04-01 | 1997-03-11 | Cortech, Inc. | Bradykinin receptor antagonists with neurokinin receptor blocking activity |
| EP0666856B1 (en) | 1992-10-28 | 2000-01-05 | MERCK SHARP & DOHME LTD. | 4-arylmethyloxymethyl piperidines as tachykinin antagonists |
| CA2150951A1 (en) | 1992-12-14 | 1994-06-23 | Angus Murray Macleod | 4-aminomethyl/thiomethyl/sulfonylmethyl-4-phenylpiperidines as tachykinin receptor antagonists |
| GB9305718D0 (en) * | 1993-03-19 | 1993-05-05 | Glaxo Group Ltd | Medicaments |
| ES2120170T3 (es) | 1994-01-13 | 1998-10-16 | Merck Sharp & Dohme | Antagonistas azaciclicos gem-disustituidos de taquiquininas. |
| PT812195E (pt) | 1995-02-28 | 2003-03-31 | Aventis Pharma Inc | Composicao farmaceutica para compostos de piperidinoalcanol |
| SE9503143D0 (sv) * | 1995-09-12 | 1995-09-12 | Astra Ab | New preparation |
| GB9601680D0 (en) | 1996-01-27 | 1996-03-27 | Pfizer Ltd | Therapeutic agents |
| WO1998002158A1 (en) | 1996-07-17 | 1998-01-22 | Merck & Co., Inc. | Alteration of circadian rhythmicity with a tachykinin antagonist |
| US6162805A (en) | 1997-04-24 | 2000-12-19 | Merck Sharp & Dohme Limited | Use of an NK-1 receptor antagonist and an SSRI for treating obesity |
| JP3571511B2 (ja) * | 1997-11-11 | 2004-09-29 | トーアエイヨー株式会社 | 経皮吸収製剤 |
| AU779073B2 (en) * | 1998-12-23 | 2005-01-06 | Nps Allelix Corp. | Indole and indolizidine derivatives for the treatment of migraine |
| MXPA01011981A (es) | 1999-05-24 | 2003-09-04 | Sonus Pharma Inc | Vehiculo de emulsion para farmacos poco solubles. |
| US6436928B1 (en) | 1999-12-17 | 2002-08-20 | Schering Corporation | Selective neurokinin antagonists |
| EP1237874B1 (en) | 1999-12-17 | 2006-02-22 | Schering Corporation | Selective neurokinin antagonists |
| US6499984B1 (en) | 2000-05-22 | 2002-12-31 | Warner-Lambert Company | Continuous production of pharmaceutical granulation |
| MY128449A (en) * | 2000-05-24 | 2007-02-28 | Sugen Inc | Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
| EP1368322A4 (en) * | 2001-02-12 | 2004-03-17 | Teva Pharma | NOVEL CRYSTALLINE FACIES OF OXCARBAZEPINE AND PROCESSES FOR THEIR PREPARATION |
| ES2291538T3 (es) | 2001-11-13 | 2008-03-01 | Schering Corporation | Antagonistas de nk1. |
| PE20030762A1 (es) * | 2001-12-18 | 2003-09-05 | Schering Corp | Compuestos heterociclicos como antagonistas nk1 |
| ATE358482T1 (de) * | 2002-07-03 | 2007-04-15 | Schering Corp | 1-amido-4-phenyl-4-benzyloxymethyl-piperidin derivative und verwandte verbindungen als neurokinin-1 (nk-1) antagonsisten zur behandlung von erbrechen, depressionen, angstzustände und husten |
| US7534913B2 (en) * | 2002-07-18 | 2009-05-19 | Teva Pharmaceutica Industries Ltd. | Crystalline form of nateglinide |
| WO2004058773A1 (en) * | 2002-12-24 | 2004-07-15 | Teva Pharmaceutical Industries Ltd. | Novel crystal forms of olanzapine, methods for their preparation and method for the preparation of known olanzapine crystal forms |
| CA2518836A1 (en) | 2003-03-13 | 2004-09-30 | Conforma Therapeutics Corporation | Drug formulations having long and medium chain triglycerides |
| GB0321256D0 (en) * | 2003-09-11 | 2003-10-08 | Generics Uk Ltd | Novel crystalline compounds |
| US7309790B2 (en) | 2003-10-03 | 2007-12-18 | Pfizer Inc | Chemical compounds |
| JP2007515425A (ja) * | 2003-12-22 | 2007-06-14 | シェーリング コーポレイション | 医薬組成物 |
| CN101006074B (zh) * | 2004-07-01 | 2012-02-15 | 欧科生医股份有限公司 | 作为nk1拮抗剂的哌啶衍生物 |
| US7871632B2 (en) * | 2004-07-12 | 2011-01-18 | Adventrx Pharmaceuticals, Inc. | Compositions for delivering highly water soluble drugs |
| WO2006060580A1 (en) * | 2004-11-30 | 2006-06-08 | Myriad Genetics, Inc. | Therapeutic formulations |
| CN100367951C (zh) * | 2005-12-16 | 2008-02-13 | 石药集团恩必普药业有限公司 | 丁苯酞静脉乳剂及其应用 |
| US20070207201A1 (en) * | 2006-03-06 | 2007-09-06 | Wyeth | Liquid and Semi-Solid Pharmaceutical Formulations and Processes |
| US7563801B2 (en) * | 2006-04-05 | 2009-07-21 | Schering Corporation | Pharmaceutical formulations: salts of 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one and treatment methods using the same |
| SG170838A1 (en) | 2006-04-05 | 2011-05-30 | Opko Health Inc | Hydrochloride salts of 8-[{1-(3,5-bis-(trifluoromethyl) phenyl) -ethoxy}- methyl] -8-phenyl-1,7-diaza-spiro[4.5] decan-2-one and preparation process therefor |
| CN101110758A (zh) | 2006-07-21 | 2008-01-23 | 华为技术有限公司 | 建立紧急会话的方法、系统及代理呼叫会话控制功能 |
| TWI426073B (zh) * | 2006-08-07 | 2014-02-11 | Palau Pharma Sa | 抗黴菌組合物 |
| EP2125802A4 (en) * | 2007-02-16 | 2014-08-20 | Debiopharm Int Sa | SALTS, PRODRUGS AND POLYMORPHES OF FAB I INHIBITORS |
| AR065802A1 (es) | 2007-03-22 | 2009-07-01 | Schering Corp | Formulaciones de comprimidos que contienen sales de 8- [( 1- ( 3,5- bis- (trifluorometil) fenil) -etoxi ) - metil) -8- fenil -1, 7- diaza- spiro [ 4,5] decan -2- ona y comprimidos elaborados a partir de estas |
| AR066191A1 (es) * | 2007-03-22 | 2009-08-05 | Schering Corp | Proceso e intermediarios para la sintesis de compuestos 8- [ ( 1- (3,5- bis- ( trifluorometil) fenil) - etoxi ) - metil]- 8 fenil - 1,7- diaza - espiro (4, 5) decan -2 ona |
| CA2736195C (en) | 2008-09-05 | 2017-05-16 | Opko Health, Inc. | Process and intermediates for the synthesis of 8-[{1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one compounds |
| MX336071B (es) | 2009-08-14 | 2016-01-06 | Opko Health Inc | Formulaciones intravenosas de antagonistas de neurocinina 1. |
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- 2010-08-12 CN CN201080046905.2A patent/CN102573475B/zh not_active Expired - Fee Related
- 2010-08-12 KR KR1020127006576A patent/KR101834577B1/ko not_active Expired - Fee Related
- 2010-08-12 RU RU2017145628A patent/RU2017145628A/ru not_active Application Discontinuation
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- 2010-08-12 CN CN201510830177.9A patent/CN105503870A/zh active Pending
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- 2010-08-12 AU AU2010282483A patent/AU2010282483B2/en not_active Ceased
- 2010-08-12 EP EP10808756.0A patent/EP2464230B1/en not_active Not-in-force
- 2010-08-12 RU RU2012109405A patent/RU2642234C2/ru not_active IP Right Cessation
- 2010-08-12 ES ES10808756.0T patent/ES2609640T3/es active Active
- 2010-08-12 CA CA2770403A patent/CA2770403C/en active Active
- 2010-08-12 SG SG10201407538WA patent/SG10201407538WA/en unknown
- 2010-08-12 BR BR112012003263A patent/BR112012003263A2/pt not_active Application Discontinuation
- 2010-08-12 EP EP16181864.6A patent/EP3143996A1/en not_active Withdrawn
- 2010-08-12 WO PCT/US2010/045317 patent/WO2011019911A1/en not_active Ceased
- 2010-08-13 TW TW104121014A patent/TW201604195A/zh unknown
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