ES2609640T3 - Formulaciones intravenosas de rolapitant - Google Patents
Formulaciones intravenosas de rolapitant Download PDFInfo
- Publication number
- ES2609640T3 ES2609640T3 ES10808756.0T ES10808756T ES2609640T3 ES 2609640 T3 ES2609640 T3 ES 2609640T3 ES 10808756 T ES10808756 T ES 10808756T ES 2609640 T3 ES2609640 T3 ES 2609640T3
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- compound
- triglyceride
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- pharmaceutically acceptable
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Landscapes
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| 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 |
| NZ571693A (en) | 2006-04-05 | 2011-12-22 | Opko Health Inc | 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 |
| HUE026148T2 (en) | 2008-09-05 | 2016-05-30 | Opko Health Inc | 8 - ({1- [3,5-bis (trifluoromethyl) phenyl] ethoxy} methyl) -8-phenyl-1,7-diaza-spiro [4,5] decane-on-compounds intermediates |
| CN105503870A (zh) | 2009-08-14 | 2016-04-20 | 欧科生医股份有限公司 | 神经激肽-1拮抗剂的静脉内制剂 |
| TW201605852A (zh) * | 2013-09-26 | 2016-02-16 | 美國禮來大藥廠 | 新穎化合物及其製備ｔａｕ造影劑及ｔａｕ造影調配物之用途 |
| 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 |
| BR112017018620A2 (pt) | 2015-03-04 | 2018-04-17 | Vanda Pharmaceuticals Inc. | método de administração de tradipitanto, e, tradipitanto. |
| US20180250270A1 (en) | 2015-09-11 | 2018-09-06 | Chase Pharmaceuticals Corporation | Muscarinic combination and its use for combating hypocholinergic disorders of the central nervous system |
| US9974742B2 (en) | 2016-02-01 | 2018-05-22 | Heron Therapeutics, Inc. | Emulsion formulations of an NK-1 receptor antagonist and uses thereof |
| EP3411013A1 (en) * | 2016-02-01 | 2018-12-12 | Heron Therapeutics, Inc. | Emulsion comprising an nk-1 receptor antagonist |
| US20190175702A1 (en) * | 2016-08-03 | 2019-06-13 | 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 |
| CN110996911B (zh) * | 2017-06-26 | 2023-01-17 | 福多兹制药公司 | 阿瑞匹坦的纳米微脂囊配制品及其方法和应用 |
| KR20250069704A (ko) | 2017-06-30 | 2025-05-19 | 체이스 테라퓨틱스 코포레이션 | 우울증을 치료하기 위한 nk-1 길항제 조성물 및 우울증 치료에 사용하는 방법 |
| 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 |
| US12421260B2 (en) * | 2019-06-28 | 2025-09-23 | Shanghai Shengdi Pharmaceutical Co., Ltd | Neurokinin-1 antagonist |
| EP4125875A1 (en) | 2020-04-03 | 2023-02-08 | NeRRe Therapeutics Limited | An nk-1 receptor antagonist for treating a disease selecting from sepsis, septic shock,, acute respiratory distress syndrome (ards) or multiple organ dysfunction syndrome (mods) |
| KR20230018485A (ko) | 2020-06-02 | 2023-02-07 | 네르 쎄라퓨틱스 리미티드 | 폐에 대한 기계적 손상에 의해 촉진된 폐 섬유증 상태의 치료에 사용하기 위한 뉴로키닌 (nk)-1 수용체 길항제 |
| CN116472048B (zh) * | 2020-12-25 | 2025-02-18 | 上海盛迪医药有限公司 | Nk1拮抗剂前药化合物与5-ht3受体拮抗剂的联用用途 |
| CN118510509A (zh) * | 2022-01-12 | 2024-08-16 | 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 |
| EP4464712A4 (en) * | 2022-01-12 | 2025-07-23 | Jiangsu Hengrui Pharmaceuticals Co Ltd | CRYSTALLINE FORM OF A NEUROKININ-1 ANTAGONIST PRODRUG COMPOUND |
| 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)
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| 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 |
| ES2141174T3 (es) | 1992-10-28 | 2000-03-16 | Merck Sharp & Dohme | 4-arilmetiloximetil piperidinas como antagonistas de taquiquinina. |
| US5661162A (en) | 1992-12-14 | 1997-08-26 | Merck Sharp & Dohme Limited | 4-aminomethyl/thiomethyl/sulfonylmethyl-4-phenylpiperdines as tachykinin receptor antagonists |
| GB9305718D0 (en) * | 1993-03-19 | 1993-05-05 | Glaxo Group Ltd | Medicaments |
| WO1995019344A1 (en) | 1994-01-13 | 1995-07-20 | Merck Sharp & Dohme Limited | Gem-disubstituted azacyclic tachykinin antagonists |
| NZ302926A (en) | 1995-02-28 | 1998-10-28 | Hoechst Marion Roussel Inc | Composition for use as antihistamines comprising piperidinoalkanol derivatives and inert ingredients |
| SE9503143D0 (sv) * | 1995-09-12 | 1995-09-12 | Astra Ab | New preparation |
| GB9601680D0 (en) | 1996-01-27 | 1996-03-27 | Pfizer Ltd | Therapeutic agents |
| CA2260269A1 (en) | 1996-07-17 | 1998-01-22 | Merck & Co., Inc. | Alteration of circadian rhythmicity with a tachykinin antagonist |
| AU735760B2 (en) | 1997-04-24 | 2001-07-12 | Merck Sharp & Dohme Limited | Use of a 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 |
| CA2356638A1 (en) | 1998-12-23 | 2000-07-06 | Nps Allelix Corp. | Indole and indolizidine derivatives for the treatment of migraine |
| EP1185301A1 (en) * | 1999-05-24 | 2002-03-13 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| EP1237874B1 (en) | 1999-12-17 | 2006-02-22 | Schering Corporation | Selective neurokinin antagonists |
| US6436928B1 (en) | 1999-12-17 | 2002-08-20 | Schering Corporation | Selective neurokinin antagonists |
| US6499984B1 (en) | 2000-05-22 | 2002-12-31 | Warner-Lambert Company | Continuous production of pharmaceutical granulation |
| MY128450A (en) * | 2000-05-24 | 2007-02-28 | Upjohn Co | 1-(pyrrolidin-1-ylmethyl)-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
| HUP0303154A3 (en) | 2001-02-12 | 2009-08-28 | Teva Pharma | New crystal forms 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 |
| US7323459B2 (en) | 2002-12-24 | 2008-01-29 | Teva Pharmaceutical Industries Ltd. | Crystal forms, methods for their preparation and method for preparation of olanzapine |
| 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 |
| ES2295924T3 (es) | 2003-10-03 | 2008-04-16 | Pfizer, Inc. | Derivados de tropano imidazopirina sustituidos con actividad antagonista de los receptores ccr5 para el tratamiento de vih y de la inflamacion. |
| CA2550432A1 (en) * | 2003-12-22 | 2005-07-14 | Schering Corporation | Pharmaceutical compositions |
| SG154443A1 (en) | 2004-07-01 | 2009-08-28 | Schering Corp | Piperidine derivatives as nk1 antagonists |
| US7871632B2 (en) | 2004-07-12 | 2011-01-18 | Adventrx Pharmaceuticals, Inc. | Compositions for delivering highly water soluble drugs |
| CA2588052A1 (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 |
| NZ571693A (en) * | 2006-04-05 | 2011-12-22 | Opko Health Inc | 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 |
| JP2010513222A (ja) | 2006-08-07 | 2010-04-30 | スティーフェル ラボラトリーズ インコーポレイテッド | 結晶抗真菌化合物 |
| EP2125802A4 (en) * | 2007-02-16 | 2014-08-20 | Debiopharm Int Sa | SALTS, PRODRUGS AND POLYMORPHES OF FAB I INHIBITORS |
| PE20081891A1 (es) | 2007-03-22 | 2008-12-27 | Opko Health Inc | 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 |
| HUE026148T2 (en) | 2008-09-05 | 2016-05-30 | Opko Health Inc | 8 - ({1- [3,5-bis (trifluoromethyl) phenyl] ethoxy} methyl) -8-phenyl-1,7-diaza-spiro [4,5] decane-on-compounds intermediates |
| CN105503870A (zh) | 2009-08-14 | 2016-04-20 | 欧科生医股份有限公司 | 神经激肽-1拮抗剂的静脉内制剂 |
-
2010
- 2010-08-12 CN CN201510830177.9A patent/CN105503870A/zh active Pending
- 2010-08-12 EP EP10808756.0A patent/EP2464230B1/en not_active Not-in-force
- 2010-08-12 WO PCT/US2010/045317 patent/WO2011019911A1/en not_active Ceased
- 2010-08-12 MX MX2012001872A patent/MX336071B/es unknown
- 2010-08-12 KR KR1020127006576A patent/KR101834577B1/ko not_active Expired - Fee Related
- 2010-08-12 ES ES10808756.0T patent/ES2609640T3/es active Active
- 2010-08-12 JP JP2012524868A patent/JP5860399B2/ja not_active Expired - Fee Related
- 2010-08-12 SG SG2012010146A patent/SG178403A1/en unknown
- 2010-08-12 BR BR112012003263A patent/BR112012003263A2/pt not_active Application Discontinuation
- 2010-08-12 SG SG10201407538WA patent/SG10201407538WA/en unknown
- 2010-08-12 CA CA2770403A patent/CA2770403C/en active Active
- 2010-08-12 AU AU2010282483A patent/AU2010282483B2/en not_active Ceased
- 2010-08-12 RU RU2012109405A patent/RU2642234C2/ru not_active IP Right Cessation
- 2010-08-12 EP EP16181864.6A patent/EP3143996A1/en not_active Withdrawn
- 2010-08-12 RU RU2017145628A patent/RU2017145628A/ru not_active Application Discontinuation
- 2010-08-12 CN CN201080046905.2A patent/CN102573475B/zh not_active Expired - Fee Related
- 2010-08-13 TW TW099127158A patent/TWI498329B/zh not_active IP Right Cessation
- 2010-08-13 TW TW104121014A patent/TW201604195A/zh unknown
- 2010-08-13 US US12/855,889 patent/US9101615B2/en active Active
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2012
- 2012-02-05 IL IL217942A patent/IL217942A0/en unknown
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2015
- 2015-07-28 US US14/811,342 patent/US20160024092A1/en not_active Abandoned
- 2015-11-04 JP JP2015216374A patent/JP6308991B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| TWI498329B (zh) | 2015-09-01 |
| CN102573475B (zh) | 2016-01-20 |
| EP2464230B1 (en) | 2016-10-05 |
| BR112012003263A2 (pt) | 2015-09-22 |
| RU2017145628A (ru) | 2019-02-19 |
| RU2012109405A (ru) | 2013-09-20 |
| TW201111382A (en) | 2011-04-01 |
| MX2012001872A (es) | 2012-04-11 |
| AU2010282483A1 (en) | 2012-03-01 |
| SG178403A1 (en) | 2012-03-29 |
| TW201604195A (zh) | 2016-02-01 |
| JP6308991B2 (ja) | 2018-04-11 |
| CN102573475A (zh) | 2012-07-11 |
| RU2642234C2 (ru) | 2018-01-24 |
| EP2464230A1 (en) | 2012-06-20 |
| US20110038925A1 (en) | 2011-02-17 |
| WO2011019911A1 (en) | 2011-02-17 |
| IL217942A0 (en) | 2012-03-29 |
| US9101615B2 (en) | 2015-08-11 |
| KR101834577B1 (ko) | 2018-03-05 |
| KR20120060215A (ko) | 2012-06-11 |
| EP3143996A1 (en) | 2017-03-22 |
| EP2464230A4 (en) | 2013-01-02 |
| MX336071B (es) | 2016-01-06 |
| US20160024092A1 (en) | 2016-01-28 |
| CN105503870A (zh) | 2016-04-20 |
| JP5860399B2 (ja) | 2016-02-16 |
| CA2770403A1 (en) | 2011-02-17 |
| SG10201407538WA (en) | 2015-01-29 |
| JP2013501806A (ja) | 2013-01-17 |
| JP2016041734A (ja) | 2016-03-31 |
| AU2010282483B2 (en) | 2014-09-04 |
| CA2770403C (en) | 2020-09-01 |
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