JP2006510618A - ノルケタミンおよびケタミン/ノルケタミンプロドラッグの鎮痛的使用 - Google Patents
ノルケタミンおよびケタミン/ノルケタミンプロドラッグの鎮痛的使用 Download PDFInfo
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- JP2006510618A JP2006510618A JP2004553852A JP2004553852A JP2006510618A JP 2006510618 A JP2006510618 A JP 2006510618A JP 2004553852 A JP2004553852 A JP 2004553852A JP 2004553852 A JP2004553852 A JP 2004553852A JP 2006510618 A JP2006510618 A JP 2006510618A
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- Prior art keywords
- norketamine
- pain
- compound
- phenyl
- ketamine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- BEQZHFIKTBVCAU-UHFFFAOYSA-N 2-amino-2-(2-chlorophenyl)-1-cyclohexanone Chemical compound C=1C=CC=C(Cl)C=1C1(N)CCCCC1=O BEQZHFIKTBVCAU-UHFFFAOYSA-N 0.000 title claims abstract description 292
- 229960003299 ketamine Drugs 0.000 title claims abstract description 187
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 title claims abstract description 178
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| PCT/US2003/036789 WO2004045601A1 (en) | 2002-11-18 | 2003-11-18 | Analgesic uses of norketamine and ketamine/norketamine prodrugs |
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| JP2006510618A true JP2006510618A (ja) | 2006-03-30 |
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| WO2019033330A1 (en) | 2017-08-17 | 2019-02-21 | Xw Laboratories, Inc. | PREPARATION AND USES OF DERIVATIVES TRACERS OF OXYGEN REACTIVE SPECIES |
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| US20200009081A1 (en) | 2017-09-13 | 2020-01-09 | Janssen Pharmaceutica N.V. | Delivery Of Esketamine For The Treatment Of Depression |
| TW201919595A (zh) * | 2017-09-27 | 2019-06-01 | 國立大學法人千葉大學 | 作為神經變性疾病或認知機能障礙之預防或治療劑之r-氯胺酮及其衍生物 |
| IL275482B1 (en) | 2017-12-22 | 2025-03-01 | Janssen Pharmaceuticals Inc | Esketamine for the treatment of depression |
| EP3505157B1 (en) | 2017-12-29 | 2021-12-08 | Celon Pharma S.A. | Dry powder ketamine composition for pulmonary administration in treatment-resistant depression |
| EP3753557B1 (en) | 2018-02-15 | 2025-11-05 | National University Corporation Chiba University | Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases |
| EP3813808A4 (en) | 2018-05-04 | 2022-01-26 | Perception Neuroscience, Inc. | Methods of treating substance abuse |
| WO2020178653A1 (en) | 2019-03-05 | 2020-09-10 | Janssen Pharmaceuticals, Inc. | Esketamine for the treatment of depression |
| WO2020237747A1 (zh) * | 2019-05-24 | 2020-12-03 | 北京大学深圳研究生院 | 一种长效化合物在制备药物中的应用 |
| US11753378B2 (en) * | 2021-04-19 | 2023-09-12 | Zevra Therapeutics, Inc. | Ketamine compounds and processes for making and using them |
| EP4289815A1 (en) | 2022-06-10 | 2023-12-13 | Pcas | Crystalline forms of norketamine |
| WO2024044355A2 (en) * | 2022-08-25 | 2024-02-29 | 1/1The Trustees Of Columbia University In The City Of New York | Compositions and methods for the treatment of alzheimer's disease and other neurogenerative disease |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5407A (en) | 1847-12-28 | Fence | ||
| US713A (en) | 1838-04-25 | Improvement in many-chambered-cylinder fire-arms | ||
| US4921475A (en) | 1983-08-18 | 1990-05-01 | Drug Delivery Systems Inc. | Transdermal drug patch with microtubes |
| US5087240A (en) | 1983-08-18 | 1992-02-11 | Drug Delivery Systems Inc. | Transdermal drug patch with conductive fibers |
| US4879119A (en) | 1984-02-21 | 1989-11-07 | Yamanouchi Pharmaceutical Co., Ltd. | Patch |
| US4671953A (en) | 1985-05-01 | 1987-06-09 | University Of Utah Research Foundation | Methods and compositions for noninvasive administration of sedatives, analgesics, and anesthetics |
| US5163899A (en) | 1987-03-20 | 1992-11-17 | Drug Delivery Systems Inc. | Transdermal drug delivery system |
| US5312325A (en) | 1987-05-28 | 1994-05-17 | Drug Delivery Systems Inc | Pulsating transdermal drug delivery system |
| GB8804164D0 (en) | 1988-02-23 | 1988-03-23 | Tucker J M | Bandage for administering physiologically active compound |
| US5008110A (en) | 1988-11-10 | 1991-04-16 | The Procter & Gamble Company | Storage-stable transdermal patch |
| US5088977A (en) | 1988-12-21 | 1992-02-18 | Drug Delivery Systems Inc. | Electrical transdermal drug applicator with counteractor and method of drug delivery |
| ATE107176T1 (de) | 1989-12-04 | 1994-07-15 | Searle & Co | System zur transdermalen albuterol applikation. |
| US5352456A (en) | 1991-10-10 | 1994-10-04 | Cygnus Therapeutic Systems | Device for administering drug transdermally which provides an initial pulse of drug |
| ATE132381T1 (de) | 1992-01-29 | 1996-01-15 | Voelkl Franz Ski | Ballspielschläger, insbesondere tennisschläger |
| SE9203743D0 (sv) | 1992-12-11 | 1992-12-11 | Astra Ab | Efficient use |
| US5543434A (en) * | 1994-02-25 | 1996-08-06 | Weg; Stuart L. | Nasal administration of ketamine to manage pain |
| ES2237767T3 (es) | 1995-04-14 | 2005-08-01 | Nektar Therapeutics | Composiciones farmaceuticas en polvo que tienen una dispersabilidad mejorada. |
| CA2230690C (en) * | 1995-08-30 | 2008-12-23 | Stuart L. Weg | Administration of ketamine to manage pain and to reduce drug dependency |
| AUPN605795A0 (en) | 1995-10-19 | 1995-11-09 | F.H. Faulding & Co. Limited | Analgesic pharmaceutical composition |
| US6248789B1 (en) | 1996-08-29 | 2001-06-19 | Stuart L. Weg | Administration of ketamine to manage pain and to reduce drug dependency |
| CA2270531C (en) * | 1996-11-05 | 2011-08-30 | Head Explorer Aps | A method for treating tension-type headache |
| AU756136B2 (en) | 1997-06-23 | 2003-01-02 | Queen's University At Kingston | Microdose therapy |
| US6630169B1 (en) | 1999-03-31 | 2003-10-07 | Nektar Therapeutics | Particulate delivery systems and methods of use |
| US6406745B1 (en) | 1999-06-07 | 2002-06-18 | Nanosphere, Inc. | Methods for coating particles and particles produced thereby |
| US6565888B1 (en) | 2000-08-23 | 2003-05-20 | Alkermes Controlled Therapeutics, Inc. | Methods and compositions for the targeted delivery of biologically active agents |
| US20050148673A1 (en) * | 2002-07-11 | 2005-07-07 | Harbut Ronald E. | Prolonged administration of NMDA antagonist and safener drug to alter neuropathic pain condition |
-
2003
- 2003-11-18 WO PCT/US2003/036789 patent/WO2004045601A1/en not_active Ceased
- 2003-11-18 JP JP2004553852A patent/JP2006510618A/ja not_active Withdrawn
- 2003-11-18 DE DE60327883T patent/DE60327883D1/de not_active Expired - Fee Related
- 2003-11-18 AT AT03783623T patent/ATE432697T1/de not_active IP Right Cessation
- 2003-11-18 NZ NZ540282A patent/NZ540282A/en unknown
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- 2003-11-18 EP EP03783623A patent/EP1567145B1/en not_active Expired - Lifetime
- 2003-11-18 EP EP08168894A patent/EP2027854A1/en not_active Withdrawn
- 2003-11-18 CA CA002506615A patent/CA2506615A1/en not_active Abandoned
- 2003-11-18 US US10/714,643 patent/US20040248964A1/en not_active Abandoned
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Also Published As
| Publication number | Publication date |
|---|---|
| CA2506615A1 (en) | 2004-06-03 |
| US20040248964A1 (en) | 2004-12-09 |
| NZ540282A (en) | 2008-06-30 |
| DE60327883D1 (de) | 2009-07-16 |
| HK1079461A1 (en) | 2006-04-07 |
| ATE432697T1 (de) | 2009-06-15 |
| EP1567145B1 (en) | 2009-06-03 |
| WO2004045601A1 (en) | 2004-06-03 |
| EP1567145A1 (en) | 2005-08-31 |
| AU2003291037A1 (en) | 2004-06-15 |
| EP2027854A1 (en) | 2009-02-25 |
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