JP2010523587A - 治療処置の副作用の低減のための方法および組成物 - Google Patents
治療処置の副作用の低減のための方法および組成物 Download PDFInfo
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- JP2010523587A JP2010523587A JP2010502274A JP2010502274A JP2010523587A JP 2010523587 A JP2010523587 A JP 2010523587A JP 2010502274 A JP2010502274 A JP 2010502274A JP 2010502274 A JP2010502274 A JP 2010502274A JP 2010523587 A JP2010523587 A JP 2010523587A
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- nicotine
- nicotinic receptor
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014508188A (ja) * | 2011-03-18 | 2014-04-03 | ノバルティス アーゲー | パーキンソン病におけるドーパミン誘発ジスキネジアに使用するためのアルファ７ニコチン性アセチルコリン受容体アクティベーターとｍＧｌｕＲ５アンタゴニストの組み合わせ剤 |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1802258A4 (en) | 2004-09-13 | 2015-09-23 | Chrono Therapeutics Inc | BIOSYNCHRONE TRANSDERMAL MEDICINES |
| US8252321B2 (en) | 2004-09-13 | 2012-08-28 | Chrono Therapeutics, Inc. | Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like |
| US7619007B2 (en) | 2004-11-23 | 2009-11-17 | Adamas Pharmaceuticals, Inc. | Method and composition for administering an NMDA receptor antagonist to a subject |
| BRPI0607017B8 (pt) | 2005-04-06 | 2021-05-25 | Adamas Pharmaceuticals Inc | composição farmacêutica compreendendo memantina e donezepil, e seu uso para o tratamento de condições relacionadas ao snc |
| US8314119B2 (en) | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| US7718677B2 (en) * | 2007-04-02 | 2010-05-18 | Parkinson's Institute | Methods and compositions for reduction of side effects of therapeutic treatments |
| WO2009146031A1 (en) * | 2008-03-31 | 2009-12-03 | University Of South Florida | Methods of treating disease-induced ataxia and non-ataxic imbalance |
| EP2300012A4 (en) * | 2008-05-23 | 2011-07-06 | Univ South Florida | METHOD FOR TREATING PERIPHERAL SENSORY NERVE LOSS WITH COMPOUNDS WITH NICOTIC ACIDYLCHOLINE RECEPTOR EFFECT |
| FR2931677B1 (fr) * | 2008-06-02 | 2010-08-20 | Sanofi Aventis | Association d'un agoniste partiel des recepteurs nicotiniques et d'un inhibiteur d'acetylcholinesterase, composition la contenant et son utilisation dans le traitement des troubles cognitifs |
| EP2233134A1 (en) | 2009-03-27 | 2010-09-29 | McNeil AB | Multi-portion intra-oral dosage form with organoleptic properties |
| TWI558398B (zh) | 2009-09-22 | 2016-11-21 | 諾華公司 | 菸鹼乙醯膽鹼受體α７活化劑之用途 |
| MX365650B (es) | 2009-12-02 | 2019-06-10 | Adamas Pharmaceuticals Inc | Composiciones de amantadina y metodos para su uso. |
| ES2537387T3 (es) * | 2009-12-04 | 2015-06-08 | Perkinelmer, Inc. | Método de uso de inhibidores de la recaptación de la dopamina y sus análogos para el tratamiento de los síntomas de la diabetes y el retraso o la prevención de las afecciones patológicas asociadas con la diabetes |
| AU2011289407B2 (en) * | 2010-08-11 | 2015-06-18 | Philadelphia Health & Education Corporation | Novel D3 dopamine receptor agonists to treat dyskinesia in Parkinson's disease |
| UA110802C2 (uk) | 2010-09-23 | 2016-02-25 | Еббві Бахамаз Лтд. | Моногідрат похідного азаадамантану |
| CA2815959C (en) | 2010-11-01 | 2020-10-06 | Intec Pharma Ltd. | Accordion pill comprising levodopa for an improved treatment of parkinson's disease symptoms |
| US20140171448A1 (en) * | 2011-01-27 | 2014-06-19 | Novartis Ag | Use of nicotinic acetylcholine receptor alpha 7 activators |
| US20130017259A1 (en) * | 2011-07-06 | 2013-01-17 | The Parkinson's Institute | Compositions and Methods for Treatment of Symptoms in Parkinson's Disease Patients |
| US20160030412A1 (en) * | 2013-02-26 | 2016-02-04 | Ari AZHIR | Compositions and methods for treatment in parkinson's disease patients |
| US10154971B2 (en) | 2013-06-17 | 2018-12-18 | Adamas Pharma, Llc | Methods of administering amantadine |
| US20150313891A1 (en) * | 2014-05-02 | 2015-11-05 | Abbvie Inc. | Neuronal nicotinic agonists and methods of use |
| JP6276429B2 (ja) * | 2014-06-18 | 2018-02-07 | イーライ リリー アンド カンパニー | ペルゴリドの経皮製剤およびその使用 |
| ES2848977T5 (es) * | 2014-10-20 | 2024-06-06 | Oyster Point Pharma Inc | Métodos de tratamiento de afecciones oculares |
| JP2018511355A (ja) | 2015-01-28 | 2018-04-26 | クロノ セラピューティクス インコーポレイテッドＣｈｒｏｎｏ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． | 薬剤送達方法及びシステム |
| CA2977814A1 (en) | 2015-03-12 | 2016-09-15 | Chrono Therapeutics Inc. | Craving input and support system |
| CN106138061B (zh) * | 2015-04-03 | 2019-06-04 | 中国人民解放军第三军医大学第三附属医院 | 预防或减弱肺纤维化的复合物及其制剂和用途 |
| US10143687B2 (en) | 2016-04-11 | 2018-12-04 | Neurocea, LLC | Compositions and methods for treatment related to fall and fall frequency in neurodegenerative diseases |
| US10292977B2 (en) | 2016-04-11 | 2019-05-21 | Neurocea, LLC | Compositions and methods for treatment related to fall and fall frequency in neurodegenerative diseases |
| US20200368175A1 (en) * | 2017-01-06 | 2020-11-26 | Chrono Therapeutics Inc. | Methods and devices for treating levodopa induced dyskinesia |
| EP3565617A1 (en) | 2017-01-06 | 2019-11-13 | Chrono Therapeutics Inc. | Transdermal drug delivery devices and methods |
| BR112020003375A2 (pt) | 2017-08-24 | 2020-08-25 | Adamas Pharma, Llc | composições de amantadina, preparações das mesmas, e métodos de uso |
| CA3101966A1 (en) | 2018-05-29 | 2019-12-05 | Morningside Venture Investments Limited | Drug delivery methods and systems |
| MA54245A (fr) | 2018-11-16 | 2022-02-23 | Morningside Venture Investments Ltd | Système d'administration transdermique de médicaments à régulation thermique |
| CA3139559A1 (en) * | 2019-05-09 | 2020-11-12 | Apkarian Technologies Llc | Methods and compositions for treating pain |
| FR3106978B1 (fr) | 2020-02-11 | 2024-04-26 | Olivier Petitjean | Utilisation d'une molecule inhibitrice de la production de ros d'origine mitochondriale telle que l'anethole trithione pour traiter la maladie de parkinson |
| CN117916589A (zh) * | 2021-09-08 | 2024-04-19 | 阿奇维生命科学公司 | 评估野靛碱纯度的分析方法 |
| WO2023057650A1 (en) | 2021-10-10 | 2023-04-13 | Centre Hospitalier Universitaire Vaudois (Chuv) | A method for predicting side effects of drugs and vaccines |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02501304A (ja) * | 1986-11-18 | 1990-05-10 | フォルシュングゲゼルシャフト・ラウヘン・ウント・ゲスンドハイト・エムベーハー | ニコチン含有流動媒質を含む口経投与用カプセル |
| US6911475B1 (en) * | 1999-09-02 | 2005-06-28 | Assistance Publique-Hopitaux De Paris | Use of nicotine or its derivatives in a drug for treating neurological disease, in particular Parkinson's disease |
| JP2006503046A (ja) * | 2002-09-16 | 2006-01-26 | スミスクライン ビーチャム コーポレーション | 放出が改変された経口製剤 |
Family Cites Families (115)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US166159A (en) * | 1875-07-27 | Improvement in calcining-kilns | ||
| US113452A (en) * | 1871-04-04 | Improvement in table-leaf supports | ||
| US77276A (en) * | 1868-04-28 | Improvement in spring and body braces for vehicles | ||
| US3845217A (en) * | 1972-11-16 | 1974-10-29 | Helsingborg L Ab | Buffered smoking substitute compositions |
| US4321387A (en) | 1980-03-21 | 1982-03-23 | Philip Morris, Incorporated | Process for the preparation of optically active nicotine analogs |
| US4332945A (en) | 1981-01-29 | 1982-06-01 | Philip Morris, Incorporated | Optically active nicotine analogs and process for their preparation |
| US4590278A (en) | 1981-01-29 | 1986-05-20 | Philip Morris Incorporated | Nicotine analogs |
| US4452984A (en) | 1981-01-29 | 1984-06-05 | Philip Morris, Inc. | Optically active nicotine analogs and process for their preparation |
| US4442292A (en) | 1981-01-29 | 1984-04-10 | Philip Morris Incorporated | Optically active nicotine analogs and process for their preparation |
| GB8301659D0 (en) * | 1983-01-21 | 1983-02-23 | Leo Ab | Smoking substitutes |
| GB8317576D0 (en) * | 1983-06-29 | 1983-08-03 | Shaw A S W | Consumer tobacco products |
| US4920989A (en) * | 1985-04-25 | 1990-05-01 | Regents Of The University Of California | Method and apparatus for aiding in the reduction of incidence of tobacco smoking |
| US4953572A (en) * | 1985-04-25 | 1990-09-04 | Rose Jed E | Method and apparatus for aiding in the reduction of incidence of tobacco smoking |
| US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
| US4992445A (en) | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
| US5001139A (en) | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
| US5073380A (en) | 1987-07-27 | 1991-12-17 | Mcneil-Ppc, Inc. | Oral sustained release pharmaceutical formulation and process |
| DE3853758T2 (de) | 1987-10-05 | 1995-09-07 | Yamanouchi Pharma Co Ltd | Heterozyklische Spiroverbindungen und ihre Herstellung. |
| IE62662B1 (en) * | 1989-01-06 | 1995-02-22 | Elan Corp Plc | Use of nicotine in the treatment of conditions susceptible to said treatment |
| US5525351A (en) * | 1989-11-07 | 1996-06-11 | Dam; Anders | Nicotine containing stimulant unit |
| US5512306A (en) * | 1992-06-19 | 1996-04-30 | Pharmica Ab | Smoking substitute |
| ATE197454T1 (de) | 1991-05-29 | 2000-11-11 | Abbott Lab | Isoxazol- und isothiazolverbindungen, die die kognitiven funktionen verbesseren |
| GB9200047D0 (en) * | 1992-01-03 | 1992-02-26 | Univ Alberta | Nicotine-containing nasal spray |
| US5242934A (en) * | 1992-03-02 | 1993-09-07 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5212188A (en) * | 1992-03-02 | 1993-05-18 | R. J. Reynolds Tabacco Company | Method for treatment of neurodegenerative diseases |
| US5227391A (en) * | 1992-04-10 | 1993-07-13 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5232933A (en) * | 1992-05-21 | 1993-08-03 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| US5248690A (en) * | 1992-07-07 | 1993-09-28 | R. J. Reynolds Tobacco Company | Method for treatment of neurodegenerative diseases |
| IL107184A (en) | 1992-10-09 | 1997-08-14 | Abbott Lab | Heterocyclic ether compounds that enhance cognitive function |
| US5549906A (en) * | 1993-07-26 | 1996-08-27 | Pharmacia Ab | Nicotine lozenge and therapeutic method for smoking cessation |
| US6121276A (en) * | 1994-04-22 | 2000-09-19 | Pentech Pharmaceuticals, Inc. | Apomorphine-containing dosage forms for ameliorating male erectile dysfunction |
| US5703100A (en) | 1994-11-10 | 1997-12-30 | Sibia Neurosciences, Inc. | Modulators of acetylcholine receptors |
| IL118279A (en) | 1995-06-07 | 2006-10-05 | Abbott Lab | Compounds 3 - Pyridyloxy (or Thio) Alkyl Heterocyclic Pharmaceutical Compositions Containing Them and Their Uses for Preparing Drugs to Control Synaptic Chemical Transmission |
| EP0853621A1 (en) | 1995-09-22 | 1998-07-22 | Novo Nordisk A/S | Novel substituted azacyclic or azabicyclic compounds |
| WO1997011073A1 (en) | 1995-09-22 | 1997-03-27 | Novo Nordisk A/S | Novel substituted azacyclic or azabicyclic compounds |
| CA2237752C (en) | 1995-11-17 | 2006-05-16 | Sibia Neurosciences, Inc. | Novel substituted aryl compounds useful as modulators of acetylcholine receptors |
| AU2340397A (en) | 1996-03-21 | 1997-10-10 | Mayo Foundation For Medical Education And Research | Use of nicotine to treat liver disease |
| US5629325A (en) | 1996-06-06 | 1997-05-13 | Abbott Laboratories | 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling chemical synaptic transmission |
| GB9614902D0 (en) * | 1996-07-16 | 1996-09-04 | Rhodes John | Sustained release composition |
| US6020335A (en) | 1997-02-06 | 2000-02-01 | Pfizer Inc | (N-(pyridinylmethyl)-heterocyclic)ylideneamine compounds as nicotinic acetylcholine receptor binding agents |
| US5861423A (en) * | 1997-02-21 | 1999-01-19 | Caldwell; William Scott | Pharmaceutical compositions incorporating aryl substituted olefinic amine compounds |
| PL335619A1 (en) | 1997-03-11 | 2000-05-08 | Darwin Discovery Ltd | Dosage forms including separate parts containing r and s enantiomers |
| FR2761072B1 (fr) | 1997-03-20 | 1999-04-23 | Synthelabo | Derives de 2,3-dihydrofuro[3,2-b]pyridine, leur preparation et leur application en therapeutique |
| US5977131A (en) | 1997-04-09 | 1999-11-02 | Pfizer Inc. | Azaindole-ethylamine derivatives as nicotinic acetylcholine receptor binding agents |
| US6024981A (en) | 1997-04-16 | 2000-02-15 | Cima Labs Inc. | Rapidly dissolving robust dosage form |
| NZ500643A (en) | 1997-05-30 | 2001-12-21 | Neurosearch As | Spiro-quinuclidine derivatives and their use in treating conditions responsive to nicotinic ACh receptor modulators |
| CA2289574C (en) | 1997-05-30 | 2007-04-24 | Neurosearch A/S | 8-azabicyclo(3,2,1)oct-2-ene and octane derivatives as cholinergic ligands at nicotinic ach receptors |
| AU736798B2 (en) | 1997-05-30 | 2001-08-02 | Neurosearch A/S | 9-Azabicyclo(3.3.1)non-2-ene and nonane derivatives as cholinergic ligands at nicotinic ACh receptors |
| DK0984943T3 (da) | 1997-05-30 | 2003-03-17 | Neurosearch As | Azacycloalkan og -alkenderivater, deres fremstilling og anvendelse |
| FR2765874B1 (fr) | 1997-07-09 | 1999-08-13 | Synthelabo | Derives de 6-pyrrolidin-2-ylpyrindines, leur preparation et leur application en therapeutique |
| AR013184A1 (es) | 1997-07-18 | 2000-12-13 | Astrazeneca Ab | Aminas heterociclicas espiroazobiciclicas, composicion farmaceutica, uso de dichas aminas para preparar medicamentos y metodo de tratamiento o profilaxis |
| US6034079A (en) * | 1997-08-11 | 2000-03-07 | University Of South Florida | Nicotine antagonists for nicotine-responsive neuropsychiatric disorders |
| ES2230723T3 (es) | 1997-10-27 | 2005-05-01 | Neurosearch A/S | Diazacicloalcanos de heteroarilo como ligandos colinergicos en recptores nicotinicos de acetilcolina. |
| ATE247104T1 (de) | 1997-11-05 | 2003-08-15 | Neurosearch As | Azaring-ether-derivate und ihre verwendung als nicotinic-ach-rezeptormodulatoren |
| US6057446A (en) * | 1998-04-02 | 2000-05-02 | Crooks; Peter Anthony | Certain 1-aza-tricyclo [3.3.1-13,7 ] decane compounds |
| EP0955301A3 (en) | 1998-04-27 | 2001-04-18 | Pfizer Products Inc. | 7-aza-bicyclo[2.2.1]-heptane derivatives, their preparation and use according to their affinity for neuronal nicotinic acetylcholine receptors |
| US6211194B1 (en) * | 1998-04-30 | 2001-04-03 | Duke University | Solution containing nicotine |
| US6232316B1 (en) * | 1998-06-16 | 2001-05-15 | Targacept, Inc. | Methods for treatment of CNS disorders |
| US6365182B1 (en) | 1998-08-12 | 2002-04-02 | Cima Labs Inc. | Organoleptically pleasant in-mouth rapidly disintegrable potassium chloride tablet |
| US6368625B1 (en) | 1998-08-12 | 2002-04-09 | Cima Labs Inc. | Orally disintegrable tablet forming a viscous slurry |
| US6562847B1 (en) | 1998-08-25 | 2003-05-13 | Ortho-Mcneil Pharmaceutical, Inc. | Pyridyl ethers and thioethers as ligands for nicotinic acetylcholine receptor and its therapeutic application |
| US6262124B1 (en) * | 1998-10-22 | 2001-07-17 | Gary Maurice Dull | Pharmaceutical compositions and methods for use |
| DE69914935T2 (de) | 1998-11-27 | 2009-10-01 | Neurosearch A/S | 8-azabicyclo[3.2.1]okt-2-en- und -oktanderivate |
| FR2786769B1 (fr) | 1998-12-04 | 2002-10-25 | Synthelabo | Derives de 2,5-diazabicyclo[2.2.1]heptane, leur preparation et leur application en therapeutique |
| FR2786770B1 (fr) | 1998-12-04 | 2001-01-19 | Synthelabo | Derives de 1,4-diazabicyclo[3.2.2.]nonane, leur preparation et leur application en therapeutique |
| CA2393437C (en) * | 1998-12-16 | 2009-12-15 | University Of South Florida | Exo-s-mecamylamine formulation and use in treatment |
| IL144340A0 (en) | 1999-01-29 | 2002-05-23 | Abbott Lab | Diazabicyclic derivatives as nicotinic acetylcholine receptor ligands |
| US6583160B2 (en) * | 1999-04-14 | 2003-06-24 | Steve Smith | Nicotine therapy method and oral carrier for assuaging tobacco-addiction |
| JP2002543070A (ja) | 1999-04-26 | 2002-12-17 | ニューロサーチ、アクティーゼルスカブ | ヘテロアリールジアザシクロアルカン類、その製造方法及びその使用方法 |
| EP1177196B1 (en) | 1999-05-04 | 2004-03-10 | Neurosearch A/S | Heteroaryl diazabicycloalkanes, their preparation and use |
| US20040229908A1 (en) | 1999-07-13 | 2004-11-18 | Jodi Nelson | Compositions and methods for the treatment of Parkinson's disease and tardive dyskinesias |
| US20080138399A1 (en) * | 1999-07-16 | 2008-06-12 | Aradigm Corporation | Dual release nicotine formulations, and systems and methods for their use |
| US8256433B2 (en) * | 1999-07-16 | 2012-09-04 | Aradigm Corporation | Systems and methods for effecting cessation of tobacco use |
| US6799576B2 (en) * | 1999-07-16 | 2004-10-05 | Aradigm Corporation | System for effecting smoking cessation |
| US20080138294A1 (en) * | 1999-07-16 | 2008-06-12 | Igor Gonda | Systems and methods for effecting cessation of tobacco use |
| US20080138398A1 (en) * | 1999-07-16 | 2008-06-12 | Aradigm Corporation | Dual release nicotine formulations, and systems and methods for their use |
| US8188043B2 (en) * | 1999-07-28 | 2012-05-29 | The Board Of Trustees Of The Leland Stanford Jr. University | Nicotine in therapeutic angiogenesis and vasculogenesis |
| SE9903998D0 (sv) * | 1999-11-03 | 1999-11-03 | Astra Ab | New compounds |
| JP2001261652A (ja) * | 2000-03-21 | 2001-09-26 | Suntory Ltd | 二置換イミノヘテロサイクリック化合物 |
| US6489025B2 (en) * | 2000-04-12 | 2002-12-03 | Showa Denko K.K. | Fine carbon fiber, method for producing the same and electrically conducting material comprising the fine carbon fiber |
| US6955821B2 (en) | 2000-04-28 | 2005-10-18 | Adams Laboratories, Inc. | Sustained release formulations of guaifenesin and additional drug ingredients |
| WO2002002081A1 (en) | 2000-07-05 | 2002-01-10 | Capricorn Pharma, Inc. | Rapid-melt semi-solid compositions, methods of making same and methods of using same |
| GB0022084D0 (en) * | 2000-09-08 | 2000-10-25 | Univ Aberdeen | Treatment of multiply antibiotic-resistant organisms |
| WO2002030392A2 (en) | 2000-10-12 | 2002-04-18 | Beecham Pharmaceuticals (Pte) Limited | Formulation containing amoxicillin |
| WO2002076211A1 (en) | 2001-03-26 | 2002-10-03 | Smithkline Beecham Corporation | Nicotine-containing oral dosage form |
| SE0102197D0 (sv) * | 2001-06-20 | 2001-06-20 | Pharmacia Ab | New product and use and manufacture thereof |
| SE0103211D0 (sv) | 2001-09-27 | 2001-09-27 | Pharmacia Ab | New formulations and use thereof |
| US20030119879A1 (en) * | 2001-10-15 | 2003-06-26 | Thomas Landh | Nicotine and chocolate compositions |
| US20030087937A1 (en) * | 2001-10-15 | 2003-05-08 | Nils-Olof Lindberg | Nicotine and cocoa powder compositions |
| US20040037879A1 (en) * | 2001-11-02 | 2004-02-26 | Adusumilli Prasad S. | Oral controlled release forms useful for reducing or preventing nicotine cravings |
| US8329217B2 (en) | 2001-11-06 | 2012-12-11 | Osmotica Kereskedelmi Es Szolgaltato Kft | Dual controlled release dosage form |
| US20040052843A1 (en) * | 2001-12-24 | 2004-03-18 | Lerner E. Itzhak | Controlled release dosage forms |
| SE0104388D0 (sv) | 2001-12-27 | 2001-12-27 | Pharmacia Ab | New formulation and use and manufacture thereof |
| US6852741B2 (en) * | 2001-12-31 | 2005-02-08 | University Of Florida | Compositions and methods for treatment of neurological disorders |
| JP2005518411A (ja) * | 2002-01-16 | 2005-06-23 | エンド ファーマシューティカルズ インコーポレーテッド | 中枢神経系の障害を治療する製薬組成物及び方法 |
| US20030159702A1 (en) * | 2002-01-21 | 2003-08-28 | Lindell Katarina E.A. | Formulation and use manufacture thereof |
| US20040166159A1 (en) * | 2002-05-29 | 2004-08-26 | Chien-Hsuan Han | Pharmaceutical dosage forms having immediate and controlled release properties that contain an aromatic amino acid decarboxylase inhibitor and levodopa |
| US7767698B2 (en) * | 2002-06-03 | 2010-08-03 | Mcneil Ab | Formulation and use thereof |
| EP1515701B1 (en) | 2002-06-17 | 2014-09-17 | Inventia Healthcare Private Limited | Process for the manufacture of multilayer tablet compositions comprising thiazolidinedione and biguanide |
| ES2708551T3 (es) * | 2002-12-20 | 2019-04-10 | Niconovum Ab | Material particulado que contiene nicotina con una celulosa cristalina |
| SE0301320D0 (sv) | 2003-05-06 | 2003-05-06 | Astrazeneca Ab | Positive modulators of nicotinic acetylcholine receptors |
| WO2004103283A2 (en) * | 2003-05-14 | 2004-12-02 | Pharmacia Corporation | Compositions of a cyclooxygenase-2 selective inhibitor and a central nervous system stimulant for the treatment of central nervous system damage |
| US7149574B2 (en) * | 2003-06-09 | 2006-12-12 | Palo Alto Investors | Treatment of conditions through electrical modulation of the autonomic nervous system |
| DE10338174A1 (de) * | 2003-08-20 | 2005-03-24 | Lts Lohmann Therapie-Systeme Ag | Transdermale Arzneimittelzubereitungen mit Wirkstoffkombinationen zur Behandlung der Parkinson-Krankheit |
| US7282217B1 (en) | 2003-08-29 | 2007-10-16 | Kv Pharmaceutical Company | Rapidly disintegrable tablets |
| DE602004019430D1 (de) * | 2003-09-08 | 2009-03-26 | Mcneil Ab | Nikotinformulierungen und ihre verwendung |
| EA200600626A1 (ru) * | 2003-10-20 | 2007-02-27 | Тева Фармасьютикал Индастриес Лтд. | Композиция и лекарственная форма продолжительного выделения леводопы |
| US20050266032A1 (en) | 2003-12-17 | 2005-12-01 | Sovereign Pharmaceuticals, Ltd. | Dosage form containing multiple drugs |
| CN1332667C (zh) * | 2004-05-26 | 2007-08-22 | 中国科学院生物物理研究所 | 一种抗帕金森症（pd）复合制剂 |
| BRPI0517494A (pt) * | 2004-12-22 | 2008-10-14 | Memory Pharm Corp | composto, composição farmacêutica, método de ativação/estimulação seletiva de receptores nicotìnicos de a-7 em um paciente em que tal ativação/estimulação tem um efeito terapêutico, método de tratamento de um paciente que sofre de uma doença psicótica, uma doença neurodegenerativa que envolve uma disfunção do sistema colinérgico, e/ou uma condição de debilitação da memória e/ou da cognição, método de tratamento de um paciente que sofre de demência e/ou uma outra condição com perda da memória, método de tratamento de um paciente que sofre de debilitação da memória devido à debilitação cognitiva suave devido ao envelhecimento, mal de alzheimer, esquizofrenia, mal de parkinson, mal de huntington, mal de pick, mal de creutzfeldt-jakob, depressão, envelhecimento, trauma na cabeça, acidente vascular cerebral, hipoxia do snc, senilidade cerebral, demência de multiinfarto, hiv e/ou doença cardiovascular, método de tratamento e/ou prevenção da demência em um paciente com o mal de alzheimer, método de tratamento de um paciente para cortar o vìcio do álcool ou o tratamento de um paciente com a terapia anti-intoxicação, método de tratamento de um paciente para propiciar neuroproteção contra os danos associados com acidentes vasculares cerebrais e isquemia e excitotoxicidade induzida por glutamatos, método de tratamento de um paciente que sofre do vìcio da nicotina, dor, tontura do fuso horário, obesidade e/ou diabetes, método de indução do ato de parar fumar em um paciente, método de tratamento de um paciente que sofre de debilitação cognitiva suave (mci), demência vascular (vad), declìnio cognitivo associado com a idade (aacd), amnésia associada com a cirurgia com o coração aberto, parada cardìaca, anestesia geral, deficiências da memória devido à exposição a agentes anestésicos, debilitação cognitiva induzida pela privação do sono, sìndrome de fadiga crÈnica, narcolepsia, demência relacionada com a aids, debilitação cognitiva relacionada com a epilepsia, sìndrome de down, demência relacionada ao alcoolismo, debilitações da memória induzidas por drogas/substáncias, demência pugilìstica (sìndrome do boxeador), ou demência animal, método para o tratamento da perda da memória, método para o tratamento de um paciente que sofre de debilitação da memória, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da disfunção da transmissão do receptor nicotìnico de acetilcolina em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante de receptores nicotìnicos de acetilcolina defeituosos ou funcionando mal em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da transmissão suprimida do receptor nicotìnico de acetilcolina em um paciente, método para o tratamento ou a profilaxia de uma doença ou de uma condição resultante da perda de sinapses colinérgicas em um paciente, método para a proteção dos neurÈnios em um paciente com neurotoxicidade induzi |
| CN101299992A (zh) | 2005-11-04 | 2008-11-05 | 伊士曼化工公司 | 药物活性物质长效输送用羧烷基纤维素酯 |
| US7958887B2 (en) * | 2006-03-10 | 2011-06-14 | Aradigm Corporation | Nozzle pore configuration for intrapulmonary delivery of aerosolized formulations |
| JP2009529343A (ja) | 2006-03-16 | 2009-08-20 | ニコノヴァム エービー | ニコチンの迅速放出を提供するチューインガム組成物 |
| US20070269492A1 (en) * | 2006-05-16 | 2007-11-22 | Per Steen | New product and use and manufacture thereof |
| US7718677B2 (en) * | 2007-04-02 | 2010-05-18 | Parkinson's Institute | Methods and compositions for reduction of side effects of therapeutic treatments |
-
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- 2008-04-02 EP EP08251288.0A patent/EP1977746B8/en not_active Not-in-force
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- 2008-04-02 CN CN201410137915.7A patent/CN103977003A/zh active Pending
- 2008-04-02 WO PCT/US2008/059174 patent/WO2008122049A2/en not_active Ceased
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- 2008-04-02 KR KR1020117012123A patent/KR20110075044A/ko not_active Withdrawn
- 2008-04-02 EP EP11152139A patent/EP2322167A1/en not_active Withdrawn
- 2008-04-02 ES ES08251288.0T patent/ES2521494T3/es active Active
- 2008-04-02 KR KR1020097022900A patent/KR101122469B1/ko not_active Expired - Fee Related
- 2008-04-02 JP JP2010502274A patent/JP2010523587A/ja not_active Withdrawn
- 2008-04-02 CA CA002682323A patent/CA2682323A1/en not_active Abandoned
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- 2009-07-14 US US12/502,992 patent/US20100029723A1/en not_active Abandoned
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-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02501304A (ja) * | 1986-11-18 | 1990-05-10 | フォルシュングゲゼルシャフト・ラウヘン・ウント・ゲスンドハイト・エムベーハー | ニコチン含有流動媒質を含む口経投与用カプセル |
| US6911475B1 (en) * | 1999-09-02 | 2005-06-28 | Assistance Publique-Hopitaux De Paris | Use of nicotine or its derivatives in a drug for treating neurological disease, in particular Parkinson's disease |
| JP2006503046A (ja) * | 2002-09-16 | 2006-01-26 | スミスクライン ビーチャム コーポレーション | 放出が改変された経口製剤 |
Non-Patent Citations (4)
| Title |
|---|
| JPN6012060538; Ａｄｖａｎｃｅｓ ｉｎ Ｂｅｈａｖｉｏｒａｌ Ｂｉｏｌｏｇｙ ５４（Ｂａｓａｌ Ｇａｎｇｌｉａ ＶＩ）, 2003, ｐ．５８９-５９８ * |
| JPN6012060540; Ｒｅｖｉｓｔａ Ｎｅｕｒｏｌｏｇｉｃａ Ａｒｇｅｎｔｉｎａ Ｖｏｌ．２７， Ｎｏ．２, 2002, ｐ．９５-９７ * |
| JPN6012060542; Ｍｏｖｅｍｅｎｔ Ｄｉｓｏｒｄｅｒｓ Ｖｏｌ．１３， Ｎｏ．４, 1998, ｐ．６３７-６４２ * |
| JPN6012060543; ＴＲＥＮＤＳ ｉｎ Ｎｅｕｒｏｓｃｉｅｎｃｅｓ Ｖｏｌ．２７， Ｎｏ．９, 2004, ｐ．５６１-５６８ * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014508188A (ja) * | 2011-03-18 | 2014-04-03 | ノバルティス アーゲー | パーキンソン病におけるドーパミン誘発ジスキネジアに使用するためのアルファ７ニコチン性アセチルコリン受容体アクティベーターとｍＧｌｕＲ５アンタゴニストの組み合わせ剤 |
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