ES2401892T3 - Compuestos morfinanos - Google Patents
Compuestos morfinanos Download PDFInfo
- Publication number
- ES2401892T3 ES2401892T3 ES11000763T ES11000763T ES2401892T3 ES 2401892 T3 ES2401892 T3 ES 2401892T3 ES 11000763 T ES11000763 T ES 11000763T ES 11000763 T ES11000763 T ES 11000763T ES 2401892 T3 ES2401892 T3 ES 2401892T3
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- quinidine
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| US8829020B2 (en) | 2009-07-16 | 2014-09-09 | Mallinckrodt Llc | Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers |
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| WO2013168015A1 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of asthma and allergy |
| WO2013167997A2 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of metabolic syndrome |
| WO2013167999A2 (en) | 2012-05-10 | 2013-11-14 | Mahesh Kandula | Compositions and methods for the treatment of neurologic diseases |
| EP2852569B1 (en) | 2012-05-23 | 2020-10-14 | Cellixbio Private Limited | Compositions and methods for the treatment of multiple sclerosis |
| US9492409B2 (en) | 2012-05-23 | 2016-11-15 | Cellix Bio Private Limited | Compositions and methods for the treatment of local pain |
| US9227974B2 (en) | 2012-05-23 | 2016-01-05 | Cellex Bio Private Limited | Compositions and methods for the treatment of respiratory disorders |
| JP2015518855A (ja) | 2012-05-23 | 2015-07-06 | セリックスビオ プライヴェート リミテッド | 粘膜炎の治療のための組成物および方法 |
| US9434729B2 (en) | 2012-05-23 | 2016-09-06 | Cellix Bio Private Limited | Compositions and methods for the treatment of periodontitis and rheumatoid arthritis |
| ES2797624T3 (es) | 2012-05-23 | 2020-12-03 | Cellix Bio Private Ltd | Composición para el tratamiento de la enfermedad inflamatoria intestinal |
| US9108942B1 (en) | 2014-11-05 | 2015-08-18 | Mahesh Kandula | Compositions and methods for the treatment of moderate to severe pain |
| WO2014020480A2 (en) | 2012-08-03 | 2014-02-06 | Mahesh Kandula | Compositions and methods for the treatment migraine and neurologic diseases |
| WO2014037833A2 (en) | 2012-09-06 | 2014-03-13 | Mahesh Kandula | Compositions and methods for the treatment inflammation and lipid disorders |
| CA2873029A1 (en) | 2012-09-08 | 2014-03-13 | Cellixbio Private Limited | Compositions and methods for the treatment of inflammation and lipid disorders |
| CN103044327B (zh) * | 2013-01-07 | 2014-12-17 | 苏州立新制药有限公司 | 一种右美沙芬的制备方法 |
| WO2014138669A1 (en) | 2013-03-07 | 2014-09-12 | Mindlab LLC | Pain medicine combination and uses thereof |
| HU231191B1 (hu) | 2013-04-15 | 2021-08-30 | Szegedi Tudományegyetem | Izotóp tartalmú morfin molekulák |
| US9333187B1 (en) | 2013-05-15 | 2016-05-10 | Cellix Bio Private Limited | Compositions and methods for the treatment of inflammatory bowel disease |
| AU2014276346A1 (en) | 2013-06-04 | 2015-12-24 | Cellixbio Private Limited | Compositions and methods for the treatment of diabetes and pre-diabetes |
| US11285146B2 (en) | 2013-11-05 | 2022-03-29 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11617728B2 (en) | 2013-11-05 | 2023-04-04 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11090300B2 (en) | 2013-11-05 | 2021-08-17 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11571399B2 (en) | 2013-11-05 | 2023-02-07 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10864209B2 (en) | 2013-11-05 | 2020-12-15 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11433067B2 (en) | 2013-11-05 | 2022-09-06 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10945973B2 (en) | 2013-11-05 | 2021-03-16 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11207281B2 (en) | 2013-11-05 | 2021-12-28 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11123343B2 (en) | 2013-11-05 | 2021-09-21 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11020389B2 (en) | 2013-11-05 | 2021-06-01 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10799497B2 (en) | 2013-11-05 | 2020-10-13 | Antecip Bioventures Ii Llc | Combination of dextromethorphan and bupropion for treating depression |
| US10786469B2 (en) | 2013-11-05 | 2020-09-29 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US20200338022A1 (en) | 2019-01-07 | 2020-10-29 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10512643B2 (en) | 2013-11-05 | 2019-12-24 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US10881657B2 (en) | 2013-11-05 | 2021-01-05 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11524007B2 (en) | 2013-11-05 | 2022-12-13 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11213521B2 (en) | 2013-11-05 | 2022-01-04 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US20160361305A1 (en) | 2013-11-05 | 2016-12-15 | Antecip Bioventures Ii Llc | Compositions and methods comprising bupropion or related compounds for sustained delivery of dextromethorphan |
| US10874663B2 (en) | 2013-11-05 | 2020-12-29 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9867819B2 (en) | 2013-11-05 | 2018-01-16 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US9457023B1 (en) | 2013-11-05 | 2016-10-04 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US11571417B2 (en) | 2013-11-05 | 2023-02-07 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11576877B2 (en) | 2013-11-05 | 2023-02-14 | Antecip Bioventures Ii Llc | Bupropion as modulator of drug activity |
| US9198905B2 (en) | 2013-11-05 | 2015-12-01 | Antecip Bioventures Ii Llc | Compositions and methods for reducing dextrorphan plasma levels and related pharmacodynamic effects |
| US11123344B2 (en) | 2013-11-05 | 2021-09-21 | Axsome Therapeutics, Inc. | Bupropion as a modulator of drug activity |
| US11185515B2 (en) | 2013-11-05 | 2021-11-30 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11510918B2 (en) | 2013-11-05 | 2022-11-29 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11229640B2 (en) | 2013-11-05 | 2022-01-25 | Antecip Bioventures Ii Llc | Combination of dextromethorphan and bupropion for treating depression |
| US10980800B2 (en) | 2013-11-05 | 2021-04-20 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11576909B2 (en) | 2013-11-05 | 2023-02-14 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9861595B2 (en) | 2013-11-05 | 2018-01-09 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US10813924B2 (en) | 2018-03-20 | 2020-10-27 | Antecip Bioventures Ii Llc | Bupropion and dextromethorphan for treating nicotine addiction |
| US11534414B2 (en) | 2013-11-05 | 2022-12-27 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11541048B2 (en) | 2013-11-05 | 2023-01-03 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11147808B2 (en) | 2013-11-05 | 2021-10-19 | Antecip Bioventures Ii Llc | Method of decreasing the fluctuation index of dextromethorphan |
| US9700528B2 (en) | 2013-11-05 | 2017-07-11 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US10966974B2 (en) | 2013-11-05 | 2021-04-06 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US20220233470A1 (en) | 2013-11-05 | 2022-07-28 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11617747B2 (en) | 2013-11-05 | 2023-04-04 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11253491B2 (en) | 2013-11-05 | 2022-02-22 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11291638B2 (en) | 2013-11-05 | 2022-04-05 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11382874B2 (en) | 2013-11-05 | 2022-07-12 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10874664B2 (en) | 2013-11-05 | 2020-12-29 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11253492B2 (en) | 2013-11-05 | 2022-02-22 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11273134B2 (en) | 2013-11-05 | 2022-03-15 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10688066B2 (en) | 2018-03-20 | 2020-06-23 | Antecip Bioventures Ii Llc | Bupropion and dextromethorphan for treating nicotine addiction |
| US11426370B2 (en) | 2013-11-05 | 2022-08-30 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US20160324807A1 (en) | 2013-11-05 | 2016-11-10 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11311534B2 (en) | 2013-11-05 | 2022-04-26 | Antecip Bio Ventures Ii Llc | Bupropion as a modulator of drug activity |
| US11541021B2 (en) | 2013-11-05 | 2023-01-03 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11344544B2 (en) | 2013-11-05 | 2022-05-31 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11129826B2 (en) | 2013-11-05 | 2021-09-28 | Axsome Therapeutics, Inc. | Bupropion as a modulator of drug activity |
| US11590124B2 (en) | 2013-11-05 | 2023-02-28 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US20200261431A1 (en) | 2019-01-07 | 2020-08-20 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11478468B2 (en) | 2013-11-05 | 2022-10-25 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10105327B2 (en) | 2013-11-05 | 2018-10-23 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphane and related pharmacodynamic effects |
| US11007189B2 (en) | 2013-11-05 | 2021-05-18 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10874665B2 (en) | 2013-11-05 | 2020-12-29 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11596627B2 (en) | 2013-11-05 | 2023-03-07 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US12109178B2 (en) | 2013-11-05 | 2024-10-08 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11273133B2 (en) | 2013-11-05 | 2022-03-15 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10105361B2 (en) | 2013-11-05 | 2018-10-23 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US11141416B2 (en) | 2013-11-05 | 2021-10-12 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11191739B2 (en) | 2013-11-05 | 2021-12-07 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11197839B2 (en) | 2013-11-05 | 2021-12-14 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11285118B2 (en) | 2013-11-05 | 2022-03-29 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11426401B2 (en) | 2013-11-05 | 2022-08-30 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9402843B2 (en) | 2013-11-05 | 2016-08-02 | Antecip Bioventures Ii Llc | Compositions and methods of using threohydroxybupropion for therapeutic purposes |
| US10933034B2 (en) | 2013-11-05 | 2021-03-02 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10894047B2 (en) | 2013-11-05 | 2021-01-19 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11291665B2 (en) | 2013-11-05 | 2022-04-05 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11096937B2 (en) | 2013-11-05 | 2021-08-24 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11065248B2 (en) | 2013-11-05 | 2021-07-20 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10966942B2 (en) | 2019-01-07 | 2021-04-06 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11419867B2 (en) | 2013-11-05 | 2022-08-23 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10940124B2 (en) | 2019-01-07 | 2021-03-09 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11234946B2 (en) | 2013-11-05 | 2022-02-01 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US12194006B2 (en) | 2013-11-05 | 2025-01-14 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11497721B2 (en) | 2013-11-05 | 2022-11-15 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9763932B2 (en) | 2013-11-05 | 2017-09-19 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US9474731B1 (en) | 2013-11-05 | 2016-10-25 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US10966941B2 (en) | 2013-11-05 | 2021-04-06 | Antecip Bioventures Ii Llp | Bupropion as a modulator of drug activity |
| US11357744B2 (en) | 2013-11-05 | 2022-06-14 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11364233B2 (en) | 2013-11-05 | 2022-06-21 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11517543B2 (en) | 2013-11-05 | 2022-12-06 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11058648B2 (en) | 2013-11-05 | 2021-07-13 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11298352B2 (en) | 2013-11-05 | 2022-04-12 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US11969421B2 (en) | 2013-11-05 | 2024-04-30 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9707191B2 (en) | 2013-11-05 | 2017-07-18 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US11298351B2 (en) | 2013-11-05 | 2022-04-12 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9968568B2 (en) | 2013-11-05 | 2018-05-15 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US10080727B2 (en) | 2013-11-05 | 2018-09-25 | Antecip Bioventures Ii Llc | Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects |
| US10772850B2 (en) | 2013-11-05 | 2020-09-15 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10898453B2 (en) | 2013-11-05 | 2021-01-26 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9457025B2 (en) | 2013-11-05 | 2016-10-04 | Antecip Bioventures Ii Llc | Compositions and methods comprising bupropion or related compounds for sustained delivery of dextromethorphan |
| US11439636B1 (en) | 2013-11-05 | 2022-09-13 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9408815B2 (en) | 2013-11-05 | 2016-08-09 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US10894046B2 (en) | 2013-11-05 | 2021-01-19 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| US9127009B2 (en) * | 2013-11-18 | 2015-09-08 | Mallinckrodt Llc | Preparation of normorphinans |
| US9096537B1 (en) | 2014-12-31 | 2015-08-04 | Mahesh Kandula | Compositions and methods for the treatment of mucositis |
| CN103833635B (zh) * | 2014-03-20 | 2015-10-14 | 武汉药谷生物工程有限公司 | 一种安全有效的镇咳药磷酸二甲啡烷的制备方法 |
| TW202106301A (zh) * | 2014-09-14 | 2021-02-16 | 美商阿瓦尼爾製藥股份有限公司 | 用於治療失智症中躁動行為之包含右旋美索芬(dextromethorphan)化合物及奎尼丁(quinidine)的藥學組成物 |
| WO2016046835A1 (en) | 2014-09-26 | 2016-03-31 | Cellix Bio Private Limited | Compositions and methods for the treatment of epilepsy and neurological disorders |
| WO2016051420A1 (en) | 2014-09-29 | 2016-04-07 | Cellix Bio Private Limited | Compositions and methods for the treatment of multiple sclerosis |
| AU2014414316B2 (en) | 2014-10-27 | 2020-04-09 | Cellix Bio Private Limited | Three component salts of fumaric acid monomethyl ester with piperazine or ethylene diamine for the treatment of multiple sclerosis |
| US9290486B1 (en) | 2014-11-05 | 2016-03-22 | Cellix Bio Private Limited | Compositions and methods for the treatment of epilepsy |
| US9284287B1 (en) | 2014-11-05 | 2016-03-15 | Cellix Bio Private Limited | Compositions and methods for the suppression of carbonic anhydrase activity |
| US9173877B1 (en) | 2014-11-05 | 2015-11-03 | Cellix Bio Private Limited | Compositions and methods for the treatment of local pain |
| US9321716B1 (en) | 2014-11-05 | 2016-04-26 | Cellix Bio Private Limited | Compositions and methods for the treatment of metabolic syndrome |
| US9150557B1 (en) | 2014-11-05 | 2015-10-06 | Cellix Bio Private Limited | Compositions and methods for the treatment of hyperglycemia |
| US9175008B1 (en) | 2014-11-05 | 2015-11-03 | Cellix Bio Private Limited | Prodrugs of anti-platelet agents |
| US10208014B2 (en) | 2014-11-05 | 2019-02-19 | Cellix Bio Private Limited | Compositions and methods for the treatment of neurological disorders |
| US9932294B2 (en) | 2014-12-01 | 2018-04-03 | Cellix Bio Private Limited | Compositions and methods for the treatment of multiple sclerosis |
| US9206111B1 (en) | 2014-12-17 | 2015-12-08 | Cellix Bio Private Limited | Compositions and methods for the treatment of neurological diseases |
| ES2905771T3 (es) | 2015-01-06 | 2022-04-12 | Cellix Bio Private Ltd | Composiciones y procedimientos para el tratamiento de la inflamación y del dolor |
| WO2017064876A1 (ja) | 2015-10-14 | 2017-04-20 | 学校法人 久留米大学 | グレリンを有効成分として含有するレット症候群（ｒｔｔ）の予防・治療剤 |
| ES2843724T3 (es) | 2015-11-30 | 2021-07-20 | Inst Nat Sante Rech Med | Antagonistas de NMDAR para el tratamiento de la angiogénesis tumoral |
| AU2017286217B2 (en) * | 2016-06-13 | 2021-06-24 | Assistance Publique - Hopitaux De Paris (Aphp) | Novel dizocilpine derivatives as peripheral NMDA receptor antagonists |
| EP3478664B1 (en) * | 2016-07-04 | 2020-12-02 | Avanir Pharmaceuticals, Inc. | Methods for the synthesis of deuterated dextromethorphan |
| US20190358208A1 (en) | 2016-09-13 | 2019-11-28 | Mindlab LLC | Medicine combinations and treatment of restless leg syndrome |
| KR20200062078A (ko) * | 2017-05-04 | 2020-06-03 | 익스시바 게엠베하 | 신규 조성물, 조합 및 그의 방법을 갖는 표적 약물 구제 |
| JP7266022B2 (ja) * | 2017-09-07 | 2023-04-27 | 大塚製薬株式会社 | ピペリジン誘導体のピペリジン窒素を重水素低級アルキルでモノアルキル化する工業的製造方法 |
| US10925842B2 (en) | 2019-01-07 | 2021-02-23 | Antecip Bioventures Ii Llc | Bupropion as a modulator of drug activity |
| EP3939954B1 (en) | 2019-03-13 | 2025-07-23 | Otsuka Pharmaceutical Co., Ltd. | Method for introducing deuterated lower alkyl into amine moiety of compound containing secondary amine |
| MX2022013427A (es) | 2020-04-27 | 2023-01-19 | Avanir Pharmaceuticals Inc | Metodos de tratamiento de la agitacion asociada a la enfermedad de alzheimer. |
| US12472156B2 (en) | 2020-06-05 | 2025-11-18 | Antecip Bioventures Ii Llc | Compounds and combinations thereof for treating neurological and psychiatric conditions |
| US12433884B2 (en) | 2020-06-05 | 2025-10-07 | Antecip Bioventures Ii Llc | Compounds and combinations thereof for treating neurological and psychiatric conditions |
| CN114340608B (zh) | 2020-07-20 | 2023-10-31 | 深圳信立泰药业股份有限公司 | 一种药物组合物及其应用 |
| CN115322150B (zh) * | 2021-05-11 | 2024-05-28 | 深圳信立泰药业股份有限公司 | 氘代右美沙芬氢溴酸盐的固体及其制备方法和医药用途 |
| IL312310A (en) | 2021-10-27 | 2024-06-01 | Avanir Pharmaceuticals Inc | Methods for treating agitation associated with Alzheimer's disease |
| US11717518B1 (en) | 2022-06-30 | 2023-08-08 | Antecip Bioventures Ii Llc | Bupropion dosage forms with reduced food and alcohol dosing effects |
| US11730706B1 (en) | 2022-07-07 | 2023-08-22 | Antecip Bioventures Ii Llc | Treatment of depression in certain patient populations |
| CN117205214B (zh) * | 2023-09-14 | 2024-10-18 | 大连医科大学 | 右美沙芬在制备治疗溃疡性结肠炎的药物中的应用 |
| WO2025242202A1 (zh) * | 2024-05-24 | 2025-11-27 | 南京迈诺威医药科技有限公司 | 氘代右美沙芬盐、晶型及其制备方法和用途 |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB713146A (en) | 1951-10-18 | 1954-08-04 | Roche Products Ltd | Anti-cough agents comprising (ú½)-3-hydroxy-n-methyl-morphinane ethers and process for the manufacture thereof |
| US4316888A (en) | 1980-04-15 | 1982-02-23 | Nelson Research & Development Co. | Method and composition of reducing pain |
| US4446140A (en) | 1981-12-10 | 1984-05-01 | Nelson Research & Development Company | Method and composition for treating mouth pain |
| JPS6089474A (ja) | 1983-10-20 | 1985-05-20 | Toyo Pharma- Kk | モルフイナン誘導体，その製造方法，及び該化合物を含有する抗腫瘍剤 |
| US4898860A (en) | 1985-08-16 | 1990-02-06 | New York University | Anticonvulsant composition and method |
| US4694010A (en) | 1985-08-16 | 1987-09-15 | New York University | Anticonvulsant compositions and method |
| US4994467A (en) | 1989-05-31 | 1991-02-19 | Zimmerman Andrew W | Treating autism and other developmental disorders in children with NMDA receptor antagonists |
| US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| US5350756A (en) | 1991-06-17 | 1994-09-27 | Smith Richard A | Use of a cytochrome oxidase inhibitor to increase the cough-suppressing activity of dextromorphan |
| US5366980A (en) | 1991-06-17 | 1994-11-22 | Smith Richard A | Use of dextromethorphan and an oxidase inhibitor to treat dermatitis |
| US5166207A (en) | 1991-06-17 | 1992-11-24 | Neurotherapeutics, Inc. | Method for enhancing the systemic delivery of dextromethorphan for the treatment of neurological disorders |
| US5336980A (en) | 1992-12-10 | 1994-08-09 | Leopold Kostal Gmbh & Co. | Apparatus and method for controlling a windshield wiping system |
| US5886026A (en) | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
| US6221335B1 (en) | 1994-03-25 | 2001-04-24 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| WO1995026325A2 (en) | 1994-03-25 | 1995-10-05 | Isotechnika Inc. | Enhancement of the efficacy of drugs by deuteration |
| DE69434794T2 (de) | 1994-09-22 | 2007-07-12 | Smith, Richard Alan, La Jolla | Kombination von dextromethorphan mit quinidine oder quinine sulfat zur behandlung verschiedener refraktärer störungen |
| US5605911A (en) | 1995-01-31 | 1997-02-25 | Washington University | Use of alpha-2 adrenergic drugs to prevent adverse effects of NMDA receptor hypofunction (NRH) |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| US6197830B1 (en) | 1995-09-22 | 2001-03-06 | Bruce M. Frome | Method for achieving relief from sympathetically mediated pain |
| AUPN605795A0 (en) | 1995-10-19 | 1995-11-09 | F.H. Faulding & Co. Limited | Analgesic pharmaceutical composition |
| CH690817A5 (de) | 1996-09-03 | 2001-01-31 | Flachsmann Ag Emil | Verfahren zur Herstellung eines stabilen, homogenen, von Folgeprodukten freien oder nahezu freien Extraktes. |
| ES2297882T3 (es) * | 1997-03-27 | 2008-05-01 | Toray Industries, Inc. | Derivados de morfinano y usos medicos de los mismos. |
| US6884429B2 (en) * | 1997-09-05 | 2005-04-26 | Isotechnika International Inc. | Medical devices incorporating deuterated rapamycin for controlled delivery thereof |
| US6440710B1 (en) | 1998-12-10 | 2002-08-27 | The Scripps Research Institute | Antibody-catalyzed deuteration, tritiation, dedeuteration or detritiation of carbonyl compounds |
| GB9925962D0 (en) | 1999-11-02 | 1999-12-29 | Novartis Ag | Organic compounds |
| DE60001623T2 (de) | 1999-12-03 | 2003-12-18 | Pfizer Products Inc., Groton | Sulfamoylheteroarylpyrazolverbindungen zur Verwendung als analgetisches/entzündungshemmendes Mittel |
| WO2001041707A2 (en) | 1999-12-08 | 2001-06-14 | Vanderbilt University | Modulation of in vivo glutamine and glycine levels in the treatment of autism |
| US20050129783A1 (en) | 2001-04-19 | 2005-06-16 | Mccleary Edward L. | Composition and method for treatment of neurophysiological conditions and maintenance of neurophysiological health |
| US6780871B2 (en) | 2001-01-29 | 2004-08-24 | Albany Medical College | Methods and compositions for treating addiction disorders |
| US6583152B2 (en) | 2001-04-30 | 2003-06-24 | Dexgen Pharmaceuticals, Inc. | Composition for reducing the risk or progression of cardiovascular diseases |
| US20040087479A1 (en) | 2001-04-30 | 2004-05-06 | Sosnowski Robert E. | Composition and method for reducing the risk or progression of cardiovascular, glaucoma, tardive dyskinesia and other diseases |
| BR0209325A (pt) | 2001-05-03 | 2004-07-20 | Hoffmann La Roche | Forma de dosagem farmacêutica de mesilato de nelfinavir amorfo |
| US6737042B2 (en) | 2001-05-24 | 2004-05-18 | Alexza Molecular Delivery Corporation | Delivery of drug esters through an inhalation route |
| TWI326214B (en) | 2002-07-17 | 2010-06-21 | Avanir Pharmaceuticals Inc | Pharmaceutical compositions comprising dextromethorphan and quinidine for the treatment of neurological disorders |
| TW200413273A (en) | 2002-11-15 | 2004-08-01 | Wako Pure Chem Ind Ltd | Heavy hydrogenation method of heterocyclic rings |
| DE102004009445A1 (de) | 2004-02-27 | 2005-09-29 | Chemetall Gmbh | Verfahren zur Herstellung von Alkyllithiumverbindungen und Aryllithiumverbindungen durch Reaktionsverfolgung mittels IR-Spektroskopie |
| US7691874B2 (en) | 2004-05-14 | 2010-04-06 | Hyoung-Chun KIM | Neuroprotective properties of dextrorotatory morphinans |
| KR20070083839A (ko) | 2004-09-29 | 2007-08-24 | 코디스 코포레이션 | 안정한 무정형 라파마이신 유사 화합물의 약학적 투약 형태 |
| US20070191411A1 (en) | 2004-10-07 | 2007-08-16 | Smith Richard A | Enhancement of impaired motor and mental functions, using dextromethorphan and oxidase enzyme inhibitor |
| US7114547B2 (en) | 2005-01-11 | 2006-10-03 | Sullivan Michael R | Casting ring |
| JP4576287B2 (ja) * | 2005-05-12 | 2010-11-04 | ゲイツ・ユニッタ・アジア株式会社 | 帆布の供給方法、配合物付き帆布の製造方法、および動力伝達ベルトの製造方法 |
| CA2615678C (en) * | 2005-07-26 | 2015-01-20 | Nycomed Gmbh | Isotopically substituted pantoprazole |
| KR101380190B1 (ko) * | 2005-07-29 | 2014-04-11 | 콘서트 파마슈티컬즈, 인크. | 벤조 〔ｄ〕〔１,３〕―디옥솔 유도체 |
| BRPI0617987A2 (pt) | 2005-10-06 | 2011-08-16 | Auspex Pharmaceuticals Inc | composição, composição farmacêutica, forma de dosagem efervescente, composição farmacêutica oral de comprimidos unitários múltiplos, forma de dosagem farmacêutica de liberação prolongada, forma de dosagem farmacêutica revestida entérica, forma de dosagem farmacêutica estável para administração oral a sujeitos mamìferos, método para tratamento de doenças relacionadas a ácido gástrico pela inibição de secreção de ácido gástrico, método para tratamento de uma infecção bacteriana provocada ou mediada por helicobacter pylori, processo para preparar um composto da fórmula 3, processo para preparar um composto da fórmula 5, uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de doenças relacionadas a ácido gástrico, pela inibição de secreção de ácido gástrico, uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de uma infecção bacteriana provocada ou mediada por helicobacter pylori uso de um composto da fórmula 1 para a preparação de um medicamento para tratamento de doenças relecionadas a ácido gástrico pela inibição de secreção de ácido gástrico |
| US7750168B2 (en) | 2006-02-10 | 2010-07-06 | Sigma-Aldrich Co. | Stabilized deuteroborane-tetrahydrofuran complex |
| JO2630B1 (en) | 2006-04-13 | 2012-06-17 | نوفارتيس ايه جي | Organic compounds |
| WO2008022285A1 (en) | 2006-08-16 | 2008-02-21 | Auspex Pharmaceuticals, Inc. | Preparation and utility of opioid analgesics |
| CA2661404A1 (en) | 2006-09-05 | 2008-03-13 | Schering Corporation | Pharmaceutical combinations for lipid management and in the treatment of atherosclerosis and hepatic steatosis |
| WO2008097924A2 (en) | 2007-02-05 | 2008-08-14 | Avanir Pharmaceuticals | Pharmaceutical compositions comprising dextromethorphan analogs for the treatment of neurological disorders |
| US20080188714A1 (en) | 2007-02-07 | 2008-08-07 | Boston Scientific Scimed, Inc. | Electromechanical in-situ cleaning of optical elements |
| MX370608B (es) * | 2007-05-01 | 2019-12-18 | Concert Pharmaceuticals Inc | Compuestos de morfinano. |
| EA023962B1 (ru) | 2008-09-19 | 2016-07-29 | Консерт Фармасьютикалз Инк. | Дейтерированные морфинановые соединения |
| US20120083487A1 (en) | 2008-10-30 | 2012-04-05 | Amanda Thomas | Combination of morphinan compounds and antidepressant for the treatment of pseudobulbar affect, neurolgical diseases, intractable and chronic pain and brain injury |
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