CN102186467B - 具有减弱释放酚类阿片样物质的药用组合物 - Google Patents

具有减弱释放酚类阿片样物质的药用组合物 Download PDF

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CN102186467B
CN102186467B CN200980141547.0A CN200980141547A CN102186467B CN 102186467 B CN102186467 B CN 102186467B CN 200980141547 A CN200980141547 A CN 200980141547A CN 102186467 B CN102186467 B CN 102186467B
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trypsin inhibitor
hydromorphone
amidino
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CN102186467A (zh
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T·E·詹金斯
J·D·赛洛基
J·W·雷
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Signature Therapeutics Inc
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CN200980141547.0A 2008-10-17 2009-10-16 具有减弱释放酚类阿片样物质的药用组合物 Active CN102186467B (zh)

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US10640008P 2008-10-17 2008-10-17
US61/106,400 2008-10-17
PCT/US2009/061068 WO2010045599A1 (en) 2008-10-17 2009-10-16 Pharmaceutical compositions with attenuated release of phenolic opioids

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Publication number Priority date Publication date Assignee Title
US8802681B2 (en) 2008-10-17 2014-08-12 Signature Therapeutics, Inc. Pharmaceutical compositions with attenuated release of phenolic opioids
WO2011008636A1 (en) * 2009-07-15 2011-01-20 Mallinckrodt Inc. 3-oxy-hydromorphone derivatives
JP2013503862A (ja) * 2009-09-08 2013-02-04 シグネーチャー セラピューティクス，インク． 酵素切断可能なケトン修飾オピオイドプロドラッグとその任意選択のインヒビターとを含んでなる組成物
US20110262359A1 (en) * 2010-04-21 2011-10-27 Jenkins Thomas E Compositions comprising enzyme-cleavable prodrugs of active agents and inhibitors thereof
US20130059914A1 (en) 2010-04-21 2013-03-07 Signature Therapeutics, Inc. Compositions Comprising Enzyme-Cleavable Amphetamine Prodrugs and Inhibitors Thereof
WO2011133151A1 (en) * 2010-04-21 2011-10-27 Pharmacofore, Inc. Compositions comprising enzyme-cleavable phenol-modified opioid prodrugs and inhibitors thereof
US9238020B2 (en) 2010-04-21 2016-01-19 Signature Therapeutics, Inc. Compositions comprising enzyme-cleavable phenol-modified tapentadol prodrug
BR112012026768A2 (pt) * 2010-04-21 2015-09-29 Signature Therapeutics Inc composições compreendendo pró-farmacos de opioides cliváveis de modo enzimático e seus inibidores.
US20110262355A1 (en) 2010-04-21 2011-10-27 Jenkins Thomas E Compositions comprising enzyme-cleavable opioid prodrugs and inhibitors thereof
WO2012096886A1 (en) * 2011-01-11 2012-07-19 Signature Therapeutics, Inc. Compositions comprising enzyme-cleavable oxycodone prodrug
WO2012096887A2 (en) * 2011-01-11 2012-07-19 Signature Therapeutics, Inc. Compositions comprising enzyme-cleavable oxycodone prodrug
US8685916B2 (en) 2011-03-09 2014-04-01 Signature Therapeutics, Inc. Opioid prodrugs with heterocyclic linkers
BR112013022946A2 (pt) 2011-03-09 2017-07-18 Signature Therapeutics Inc pró-fármacos de agentes ativos com ligantes heterocíclocos
US10314839B2 (en) 2014-10-20 2019-06-11 Elysium Therapeutics, Inc. Diversion-resistant opioid formulations
US11634384B2 (en) 2014-11-25 2023-04-25 Concentric Analgesics, Inc. Prodrugs of phenolic TRPV1 agonists
US10335406B2 (en) * 2015-10-01 2019-07-02 Elysium Therapeutics, Inc. Opioid compositions resistant to overdose and abuse
AU2016332071B2 (en) * 2015-10-01 2019-04-18 Elysium Therapeutics, Inc. Polysubunit opioid prodrugs resistant to overdose and abuse
JP2019516773A (ja) 2016-05-25 2019-06-20 コンセントリック アナルジジックス，インク． 改善された局所麻酔のための局所麻酔薬及び血管収縮薬と組み合わせたフェノールｔｒｐｖ１アゴニストのプロドラッグ
AU2018234911B2 (en) * 2017-03-17 2024-04-18 Elysium Therapeutics, Inc. Polysubunit opioid prodrugs resistant to overdose and abuse
TW202019887A (zh) 2018-07-27 2020-06-01 美商同心止痛劑股份有限公司 酚系trpv1促效劑之聚乙二醇化前藥
EP3934635A4 (en) 2019-03-06 2022-12-07 Ensysce Biosciences, Inc. COMPOSITIONS OF ENZYME-CLEAVABLE AMPHETAMINE PRODRUGS AND INHIBITORS THEREOF
WO2022192197A1 (en) * 2021-03-09 2022-09-15 Ensysce Biosciences Inc. Compositions comprising enzyme-cleavable prodrugs and controlled release nafamostat and methods of use thereof
MX2024003466A (es) 2021-09-29 2024-06-04 Ensysce Biosciences Inc Profarmacos de metadona escindibles por enzimas y metodos de uso de los mismos.

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007140272A2 (en) * 2006-05-26 2007-12-06 Pharmacofore, Inc. Controlled release of phenolic opioids

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU527371B2 (en) 1980-09-16 1983-03-03 Torii & Co., Ltd. Amidine
US5109118A (en) * 1989-07-06 1992-04-28 Yutaka Mizushima Modified biologically active proteins
CA2032420A1 (en) 1989-12-22 1991-06-23 Akira Okuyama Guanidinobenzene derivatives
US6692766B1 (en) 1994-06-15 2004-02-17 Yissum Research Development Company Of The Hebrew University Of Jerusalem Controlled release oral drug delivery system
BR9607492A (pt) * 1995-01-16 1999-06-29 Commw Scient Ind Res Org Conjugados de ácidos graxos de composto terapêutico
WO1997037969A1 (en) 1996-04-10 1997-10-16 Ono Pharmaceutical Co., Ltd. Tryptase inhibitor and novel guanidino derivatives
CA2353872C (en) 1998-12-15 2011-05-03 Tropix, Inc. Multiple enzyme assays
US6849263B2 (en) * 1998-12-21 2005-02-01 Generex Pharmaceutical Incorporated Pharmaceutical compositions for buccal delivery of pain relief medications
AU3000800A (en) 1999-02-18 2000-09-04 Supergen, Inc. Phosphocholine linked prodrug derivatives
US7060708B2 (en) 1999-03-10 2006-06-13 New River Pharmaceuticals Inc. Active agent delivery systems and methods for protecting and administering active agents
US20030180352A1 (en) * 1999-11-23 2003-09-25 Patel Mahesh V. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
DE60239679D1 (de) 2001-06-11 2011-05-19 Medarex Inc Methode für die ausarbeitung von cd10-aktivierten prodrug-verbindungen
US7375082B2 (en) 2002-02-22 2008-05-20 Shire Llc Abuse-resistant hydrocodone compounds
US7169752B2 (en) 2003-09-30 2007-01-30 New River Pharmaceuticals Inc. Compounds and compositions for prevention of overdose of oxycodone
US20100092562A1 (en) 2002-11-26 2010-04-15 Hollenbeck R Gary Sustained-release drug delivery compositions and methods
BRPI0410792B8 (pt) 2003-05-29 2021-05-25 New River Pharmaceuticals Inc compostos de anfetamina resistentes à dependencia
WO2007022535A2 (en) 2005-08-19 2007-02-22 Pharmacofore, Inc. Prodrugs of active agents
WO2007025286A2 (en) * 2005-08-26 2007-03-01 The Board Of Trustees Of The Leland Stanford Junior University Therapy procedure for drug delivery for trigeminal pain
CN101309917B (zh) 2005-10-06 2013-09-11 奥斯拜客斯制药有限公司 具有增强治疗性质的胃h+，k+-atp酶氘代抑制剂
RU2429223C2 (ru) 2005-12-05 2011-09-20 Ксенопорт, Инк. Мезилатное пролекарство леводопы, его композиции и применение
JP2009533459A (ja) 2006-04-14 2009-09-17 シャイア エルエルシー 共有結合する化合物の鎮痛作用の増強と、有害な副作用の減衰と、前記化合物の乱用の予防とのための組成物及び方法
TWI401237B (zh) 2006-07-24 2013-07-11 ３-〔（１ｒ，２ｒ）-３-（二甲基氨基）-１-乙基-２-甲基丙基〕酚之製備
WO2008101202A1 (en) * 2007-02-16 2008-08-21 Pharmacofore, Inc. N-17-alkylated prodrugs of opioids
US20110105381A2 (en) 2007-02-16 2011-05-05 Pharmacofore, Inc. Prodrugs of Peripheral Phenolic Opioid Antagonists
PL2596784T3 (pl) 2007-11-23 2017-06-30 Grünenthal GmbH Kompozycje tapentadolu
US9023860B2 (en) 2007-11-26 2015-05-05 Signature Therapeutics, Inc. Pro-drugs for controlled release of biologically active compounds
US20090186832A1 (en) 2008-01-18 2009-07-23 Shire Llc Amino acid peptide pro-drugs of phenolic analgesics and uses thereof
AU2009214500B2 (en) 2008-02-14 2014-10-23 Alkermes, Inc. Selective opioid compounds
US8802681B2 (en) 2008-10-17 2014-08-12 Signature Therapeutics, Inc. Pharmaceutical compositions with attenuated release of phenolic opioids
US20100227921A1 (en) 2009-03-03 2010-09-09 Shire Llc Amino acid and peptide carbamate prodrugs of tapentadol and uses thereof
AU2010231126A1 (en) 2009-04-02 2011-10-13 Shire Llc Novel dicarboxylic acid linked amino acid and peptide prodrugs of opioids and uses thereof
JP2013527124A (ja) 2009-07-17 2013-06-27 シャイア エルエルシー オピオイドの新規カルバマートアミノ酸およびペプチドプロドラッグならびにその使用
EP2560491A1 (en) 2010-04-21 2013-02-27 Signature Therapeutics, Inc. Peripheral opioid agonists and peripheral opioid antagonists

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007140272A2 (en) * 2006-05-26 2007-12-06 Pharmacofore, Inc. Controlled release of phenolic opioids

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