JP2014505736A - 固体投薬形態の乱用を防止するための技術 - Google Patents
固体投薬形態の乱用を防止するための技術 Download PDFInfo
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US201161443966P | 2011-02-17 | 2011-02-17 | |
| US61/443,966 | 2011-02-17 | ||
| PCT/US2012/025737 WO2012112952A1 (en) | 2011-02-17 | 2012-02-17 | Technology for preventing abuse of solid dosage forms |
Publications (2)
| Publication Number | Publication Date |
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| JP2014505736A true JP2014505736A (ja) | 2014-03-06 |
| JP2014505736A5 JP2014505736A5 (enExample) | 2015-04-09 |
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| JP2013554661A Pending JP2014505736A (ja) | 2011-02-17 | 2012-02-17 | 固体投薬形態の乱用を防止するための技術 |
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| EP (1) | EP2675436A1 (enExample) |
| JP (1) | JP2014505736A (enExample) |
| CN (1) | CN103476401A (enExample) |
| AU (1) | AU2012219322A1 (enExample) |
| BR (1) | BR112013021026A2 (enExample) |
| CA (1) | CA2827273A1 (enExample) |
| IL (1) | IL227962A0 (enExample) |
| MX (1) | MX2013009492A (enExample) |
| WO (1) | WO2012112952A1 (enExample) |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005500364A (ja) * | 2001-08-06 | 2005-01-06 | ユーロ−セルティーク，エス．エイ． | オピオイドの乱用を防止する組成物と方法 |
| JP2005501067A (ja) * | 2001-08-06 | 2005-01-13 | ユーロ−セルティーク，エス．エイ． | オピオイドの乱用を防ぐための組成物および方法 |
| JP2005523876A (ja) * | 2001-09-26 | 2005-08-11 | ペンウェスト ファーマシューティカルズ カンパニー | 乱用の可能性が低減したオピオイド製剤 |
| JP2006506374A (ja) * | 2002-10-25 | 2006-02-23 | グリューネンタ−ル・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 乱用が防止された製剤 |
| US20060110327A1 (en) * | 2004-11-24 | 2006-05-25 | Acura Pharmaceuticals, Inc. | Methods and compositions for deterring abuse of orally administered pharmaceutical products |
| JP2009537456A (ja) * | 2005-11-10 | 2009-10-29 | フラメル・テクノロジーズ | 誤用防止微粒子経口医薬形態 |
| WO2010066034A1 (en) * | 2008-12-12 | 2010-06-17 | Paladin Labs Inc. | Methadone formulation |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773955A (en) | 1970-08-03 | 1973-11-20 | Bristol Myers Co | Analgetic compositions |
| US3966940A (en) | 1973-11-09 | 1976-06-29 | Bristol-Myers Company | Analgetic compositions |
| US20030118641A1 (en) * | 2000-07-27 | 2003-06-26 | Roxane Laboratories, Inc. | Abuse-resistant sustained-release opioid formulation |
| SI1299104T1 (sl) | 2000-02-08 | 2009-10-31 | Euro Celtique Sa | Oralne formulacije opioidnih agonistov, varne pred zlorabo |
| US20030068375A1 (en) * | 2001-08-06 | 2003-04-10 | Curtis Wright | Pharmaceutical formulation containing gelling agent |
| US7332182B2 (en) * | 2001-08-06 | 2008-02-19 | Purdue Pharma L.P. | Pharmaceutical formulation containing opioid agonist, opioid antagonist and irritant |
| WO2004000280A1 (en) * | 2002-04-29 | 2003-12-31 | Shire Laboraties, Inc. | Pharmaceutical formulations with improved bioavailability |
| EP2422773A3 (en) * | 2002-09-20 | 2012-04-18 | Alpharma, Inc. | Sequestering subunit and related compositions and methods |
| US7201920B2 (en) * | 2003-11-26 | 2007-04-10 | Acura Pharmaceuticals, Inc. | Methods and compositions for deterring abuse of opioid containing dosage forms |
| CA2916869A1 (en) | 2004-06-12 | 2005-12-29 | Jane C. Hirsh | Abuse-deterrent drug formulations |
| US8652529B2 (en) * | 2005-11-10 | 2014-02-18 | Flamel Technologies | Anti-misuse microparticulate oral pharmaceutical form |
-
2012
- 2012-02-17 WO PCT/US2012/025737 patent/WO2012112952A1/en not_active Ceased
- 2012-02-17 US US13/400,004 patent/US20120321716A1/en not_active Abandoned
- 2012-02-17 AU AU2012219322A patent/AU2012219322A1/en not_active Abandoned
- 2012-02-17 CN CN2012800187591A patent/CN103476401A/zh active Pending
- 2012-02-17 CA CA2827273A patent/CA2827273A1/en not_active Abandoned
- 2012-02-17 MX MX2013009492A patent/MX2013009492A/es not_active Application Discontinuation
- 2012-02-17 BR BR112013021026A patent/BR112013021026A2/pt not_active IP Right Cessation
- 2012-02-17 EP EP12712786.8A patent/EP2675436A1/en not_active Withdrawn
- 2012-02-17 JP JP2013554661A patent/JP2014505736A/ja active Pending
-
2013
- 2013-08-14 IL IL227962A patent/IL227962A0/en unknown
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005500364A (ja) * | 2001-08-06 | 2005-01-06 | ユーロ−セルティーク，エス．エイ． | オピオイドの乱用を防止する組成物と方法 |
| JP2005501067A (ja) * | 2001-08-06 | 2005-01-13 | ユーロ−セルティーク，エス．エイ． | オピオイドの乱用を防ぐための組成物および方法 |
| JP2005523876A (ja) * | 2001-09-26 | 2005-08-11 | ペンウェスト ファーマシューティカルズ カンパニー | 乱用の可能性が低減したオピオイド製剤 |
| JP2006506374A (ja) * | 2002-10-25 | 2006-02-23 | グリューネンタ−ル・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 乱用が防止された製剤 |
| US20060110327A1 (en) * | 2004-11-24 | 2006-05-25 | Acura Pharmaceuticals, Inc. | Methods and compositions for deterring abuse of orally administered pharmaceutical products |
| JP2009537456A (ja) * | 2005-11-10 | 2009-10-29 | フラメル・テクノロジーズ | 誤用防止微粒子経口医薬形態 |
| WO2010066034A1 (en) * | 2008-12-12 | 2010-06-17 | Paladin Labs Inc. | Methadone formulation |
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| US9675610B2 (en) | 2002-06-17 | 2017-06-13 | Grünenthal GmbH | Abuse-proofed dosage form |
| US10369109B2 (en) | 2002-06-17 | 2019-08-06 | Grünenthal GmbH | Abuse-proofed dosage form |
| US10058548B2 (en) | 2003-08-06 | 2018-08-28 | Grünenthal GmbH | Abuse-proofed dosage form |
| US9629807B2 (en) | 2003-08-06 | 2017-04-25 | Grünenthal GmbH | Abuse-proofed dosage form |
| US10130591B2 (en) | 2003-08-06 | 2018-11-20 | Grünenthal GmbH | Abuse-proofed dosage form |
| US11224576B2 (en) | 2003-12-24 | 2022-01-18 | Grünenthal GmbH | Process for the production of an abuse-proofed dosage form |
| US11844865B2 (en) | 2004-07-01 | 2023-12-19 | Grünenthal GmbH | Abuse-proofed oral dosage form |
| US10729658B2 (en) | 2005-02-04 | 2020-08-04 | Grünenthal GmbH | Process for the production of an abuse-proofed dosage form |
| US10675278B2 (en) | 2005-02-04 | 2020-06-09 | Grünenthal GmbH | Crush resistant delayed-release dosage forms |
| US9750701B2 (en) | 2008-01-25 | 2017-09-05 | Grünenthal GmbH | Pharmaceutical dosage form |
| US10493033B2 (en) | 2009-07-22 | 2019-12-03 | Grünenthal GmbH | Oxidation-stabilized tamper-resistant dosage form |
| US10080721B2 (en) | 2009-07-22 | 2018-09-25 | Gruenenthal Gmbh | Hot-melt extruded pharmaceutical dosage form |
| US9925146B2 (en) | 2009-07-22 | 2018-03-27 | Grünenthal GmbH | Oxidation-stabilized tamper-resistant dosage form |
| US10300141B2 (en) | 2010-09-02 | 2019-05-28 | Grünenthal GmbH | Tamper resistant dosage form comprising inorganic salt |
| US9636303B2 (en) | 2010-09-02 | 2017-05-02 | Gruenenthal Gmbh | Tamper resistant dosage form comprising an anionic polymer |
| US10864164B2 (en) | 2011-07-29 | 2020-12-15 | Grünenthal GmbH | Tamper-resistant tablet providing immediate drug release |
| US10695297B2 (en) | 2011-07-29 | 2020-06-30 | Grünenthal GmbH | Tamper-resistant tablet providing immediate drug release |
| US10201502B2 (en) | 2011-07-29 | 2019-02-12 | Gruenenthal Gmbh | Tamper-resistant tablet providing immediate drug release |
| JP2014533668A (ja) * | 2011-11-17 | 2014-12-15 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 薬理学的に活性な成分、オピオイドアンタゴニストおよび／または嫌忌剤（ａｖｅｒｓｉｖｅａｇｅｎｔ）、ポリアルキレンオキシドおよび陰イオン性ポリマーを含むタンパーレジスタント経口医薬剤形 |
| US9655853B2 (en) | 2012-02-28 | 2017-05-23 | Grünenthal GmbH | Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer |
| US10335373B2 (en) | 2012-04-18 | 2019-07-02 | Grunenthal Gmbh | Tamper resistant and dose-dumping resistant pharmaceutical dosage form |
| US10064945B2 (en) | 2012-05-11 | 2018-09-04 | Gruenenthal Gmbh | Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc |
| US9737490B2 (en) | 2013-05-29 | 2017-08-22 | Grünenthal GmbH | Tamper resistant dosage form with bimodal release profile |
| US10154966B2 (en) | 2013-05-29 | 2018-12-18 | Grünenthal GmbH | Tamper-resistant dosage form containing one or more particles |
| US10624862B2 (en) | 2013-07-12 | 2020-04-21 | Grünenthal GmbH | Tamper-resistant dosage form containing ethylene-vinyl acetate polymer |
| US10449547B2 (en) | 2013-11-26 | 2019-10-22 | Grünenthal GmbH | Preparation of a powdery pharmaceutical composition by means of cryo-milling |
| US9913814B2 (en) | 2014-05-12 | 2018-03-13 | Grünenthal GmbH | Tamper resistant immediate release capsule formulation comprising tapentadol |
| US9872835B2 (en) | 2014-05-26 | 2018-01-23 | Grünenthal GmbH | Multiparticles safeguarded against ethanolic dose-dumping |
| US10888528B2 (en) | 2014-12-08 | 2021-01-12 | Clexio Biosciences Ltd. | Immediate release abuse-deterrent granulated dosage forms |
| US11534409B2 (en) | 2014-12-08 | 2022-12-27 | Clexio Biosciences Ltd. | Immediate release abuse-deterrent granulated dosage forms |
| US11730702B2 (en) | 2014-12-08 | 2023-08-22 | Clexio Biosciences, Ltd. | Immediate release abuse-deterrent granulated dosage forms |
| JP2017537168A (ja) * | 2014-12-08 | 2017-12-14 | シーマ・ラブス・インコーポレーテッド | 即放性乱用抑止性顆粒剤形 |
| US9855263B2 (en) | 2015-04-24 | 2018-01-02 | Grünenthal GmbH | Tamper-resistant dosage form with immediate release and resistance against solvent extraction |
| US10842750B2 (en) | 2015-09-10 | 2020-11-24 | Grünenthal GmbH | Protecting oral overdose with abuse deterrent immediate release formulations |
| JP2020524697A (ja) * | 2017-06-23 | 2020-08-20 | サン、ファーマ、アドバンスト、リサーチ、カンパニー、リミテッドＳｕｎ Ｐｈａｒｍａ Ａｄｖａｎｃｅｄ Ｒｅｓｅａｒｃｈ Ｃｏｍｐａｎｙ Ｌｉｍｉｔｅｄ | 乱用抑止経口固体投与形態 |
| JP7125436B2 (ja) | 2017-06-23 | 2022-08-24 | サン、ファーマ、アドバンスト、リサーチ、カンパニー、リミテッド | 乱用抑止経口固体投与形態 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2675436A1 (en) | 2013-12-25 |
| MX2013009492A (es) | 2014-07-30 |
| WO2012112952A1 (en) | 2012-08-23 |
| CA2827273A1 (en) | 2012-08-23 |
| BR112013021026A2 (pt) | 2016-10-11 |
| IL227962A0 (en) | 2013-09-30 |
| AU2012219322A1 (en) | 2013-05-09 |
| US20120321716A1 (en) | 2012-12-20 |
| CN103476401A (zh) | 2013-12-25 |
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