KR20170102571A - 오피오이드 과다투여에 의해 유도된 호흡 저하를 약화시키기 위한 제제 및 방법 - Google Patents
오피오이드 과다투여에 의해 유도된 호흡 저하를 약화시키기 위한 제제 및 방법 Download PDFInfo
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- KR20170102571A KR20170102571A KR1020177024247A KR20177024247A KR20170102571A KR 20170102571 A KR20170102571 A KR 20170102571A KR 1020177024247 A KR1020177024247 A KR 1020177024247A KR 20177024247 A KR20177024247 A KR 20177024247A KR 20170102571 A KR20170102571 A KR 20170102571A
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- naltrexone
- opioid
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- respiratory depression
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| EP3393470B1 (en) | 2015-12-22 | 2021-01-20 | Zogenix International Limited | Metabolism resistant fenfluramine analogs and methods of using the same |
| WO2017180659A1 (en) * | 2016-04-11 | 2017-10-19 | Arizona Board Of Regents On Behalf Of University Of Arizona | Opioid receptor modulators |
| US10335405B1 (en) | 2016-05-04 | 2019-07-02 | Patheon Softgels, Inc. | Non-burst releasing pharmaceutical composition |
| KR20250040753A (ko) | 2016-08-24 | 2025-03-24 | 조게닉스 인터내셔널 리미티드 | 5-ht2b 작용물질의 형성을 억제하기 위한 제제 및 그것의 사용 방법 |
| US10335375B2 (en) | 2017-05-30 | 2019-07-02 | Patheon Softgels, Inc. | Anti-overingestion abuse deterrent compositions |
| US10682317B2 (en) | 2017-09-26 | 2020-06-16 | Zogenix International Limited | Ketogenic diet compatible fenfluramine formulation |
| EP3727384A4 (en) | 2017-12-20 | 2021-11-03 | Purdue Pharma L.P. | ABUSE-DISSUASIVE MORPHINE SULPHATE FORMES |
| EP3790537A1 (en) | 2018-05-11 | 2021-03-17 | Zogenix International Limited | Compositions and methods for treating seizure-induced sudden death |
| WO2019241005A1 (en) * | 2018-06-14 | 2019-12-19 | Zogenix International Limited | Compositions and methods for treating respiratory depression with fenfluramine |
| EP3883555A1 (en) | 2018-11-19 | 2021-09-29 | Zogenix International Limited | Methods of treating rett syndrome using fenfluramine |
| US20240100120A1 (en) * | 2019-10-11 | 2024-03-28 | Board Of Regents, The University Of Taxas System | Compositions and methods for preventing, reducing and reversing opioid-induced respiratory depression |
| US11612574B2 (en) | 2020-07-17 | 2023-03-28 | Zogenix International Limited | Method of treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) |
| AU2022380482A1 (en) | 2021-11-02 | 2024-05-16 | Enalare Therapeutics Inc. | Methods of treating respiratory depression modulated by a non-opioid agent |
| US12303604B1 (en) | 2024-10-16 | 2025-05-20 | Currax Pharmaceuticals Llc | Pharmaceutical formulations comprising naltrexone and/or bupropion |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL367427A1 (en) * | 2001-08-06 | 2005-02-21 | Euro-Celtique S.A. | Opioid agonist formulations with releasable and sequestered antagonist |
| AU2004296821B2 (en) * | 2003-12-05 | 2011-05-12 | Carefusion 303, Inc. | Patient-controlled analgesia with patient monitoring system |
| EP1931593A4 (en) | 2005-10-07 | 2009-04-22 | Univ Florida | MULTIPLE COMPONENT NANOPARTICLES FOR MULTIPLEX SIGNALING AND OPTICAL CODING |
| JP2010506833A (ja) * | 2006-10-11 | 2010-03-04 | アルファーマ，インコーポレイテッド | 医薬組成物 |
| EP2197427A2 (en) * | 2007-09-04 | 2010-06-23 | Alpharma, Inc. | A multilayer pharmaceutical composition comprising an antagonist in a first layer and an agonist in a second layer |
| EP2224805A4 (en) * | 2007-12-17 | 2013-10-16 | Alpharma Pharmaceuticals Llc | PHARMACEUTICAL COMPOSITION |
| US8623418B2 (en) * | 2007-12-17 | 2014-01-07 | Alpharma Pharmaceuticals Llc | Pharmaceutical composition |
| CN102231991A (zh) | 2008-07-31 | 2011-11-02 | 生物工程大学精神物质实验室 | 应用于生物分析的活性粒子及其制备方法 |
| IT1391530B1 (it) | 2008-07-31 | 2012-01-11 | Cyanagen S R L | Particelle attive per applicazioni bio-analitiche e metodi per la loro preparazione |
| KR20170102571A (ko) * | 2010-10-26 | 2017-09-11 | 알파마 파머슈티컬스 엘엘씨 | 오피오이드 과다투여에 의해 유도된 호흡 저하를 약화시키기 위한 제제 및 방법 |
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| US20140030343A1 (en) | 2014-01-30 |
| KR20130097211A (ko) | 2013-09-02 |
| EP2632442A2 (en) | 2013-09-04 |
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| RU2541159C2 (ru) | 2015-02-10 |
| BR112013009267A2 (pt) | 2016-07-26 |
| US20160045449A1 (en) | 2016-02-18 |
| SG189234A1 (en) | 2013-05-31 |
| IL225966A0 (en) | 2013-06-27 |
| ZA201302363B (en) | 2014-06-25 |
| JP2013540807A (ja) | 2013-11-07 |
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| AU2011322147A1 (en) | 2013-04-18 |
| MX2013003832A (es) | 2013-10-01 |
| CN103189055A (zh) | 2013-07-03 |
| US20170367987A1 (en) | 2017-12-28 |
| KR20160017668A (ko) | 2016-02-16 |
| CA2814230A1 (en) | 2012-05-03 |
| RU2013117274A (ru) | 2014-12-10 |
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