LT4455B - N-propargil-1-aminoindano r-entantiomero, jo druskų ir jo kompozicijų panaudojimas - Google Patents
N-propargil-1-aminoindano r-entantiomero, jo druskų ir jo kompozicijų panaudojimas Download PDFInfo
- Publication number
- LT4455B LT4455B LT97-200A LT97200A LT4455B LT 4455 B LT4455 B LT 4455B LT 97200 A LT97200 A LT 97200A LT 4455 B LT4455 B LT 4455B
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- Lithuania
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- pai
- aminoindan
- propargyl
- mao
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P25/20—Hypnotics; Sedatives
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- Health & Medical Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
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- General Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Anesthesiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/446,439 US5744500A (en) | 1990-01-03 | 1995-05-22 | Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LT97200A LT97200A (en) | 1998-09-25 |
| LT4455B true LT4455B (lt) | 1999-01-25 |
Family
ID=23772591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LT97-200A LT4455B (lt) | 1995-05-22 | 1997-12-22 | N-propargil-1-aminoindano r-entantiomero, jo druskų ir jo kompozicijų panaudojimas |
Country Status (21)
| Country | Link |
|---|---|
| US (6) | US5744500A (he) |
| EP (1) | EP0828485A4 (he) |
| JP (1) | JP3341898B2 (he) |
| KR (1) | KR100412154B1 (he) |
| CN (1) | CN1096853C (he) |
| AU (1) | AU699090B2 (he) |
| BR (1) | BR9608733A (he) |
| CA (1) | CA2221458A1 (he) |
| CZ (1) | CZ288724B6 (he) |
| EE (1) | EE03741B1 (he) |
| HU (1) | HUP9901629A3 (he) |
| IL (1) | IL118247A (he) |
| LT (1) | LT4455B (he) |
| LV (1) | LV12083B (he) |
| MX (1) | MX9708977A (he) |
| NO (1) | NO975331L (he) |
| NZ (1) | NZ308866A (he) |
| PL (1) | PL184124B1 (he) |
| RU (1) | RU2203653C2 (he) |
| SK (1) | SK283675B6 (he) |
| WO (1) | WO1996037199A1 (he) |
Families Citing this family (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5744500A (en) * | 1990-01-03 | 1998-04-28 | Teva Pharmaceutical Industries, Ltd. | Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof |
| US5844003A (en) * | 1991-04-04 | 1998-12-01 | Innovations Foundation | Use of deprenyl compounds to maintain, prevent loss, or recover nerve cell function |
| US5914349A (en) * | 1994-01-10 | 1999-06-22 | Teva Pharmaceutical Industries, Ltd. | Compositions containing and methods of using 1-aminoindan and derivatives thereof and process for preparing optically active 1-aminoindan derivatives |
| US5726969A (en) * | 1994-12-28 | 1998-03-10 | Matsushita Electric Industrial Co., Ltd. | Optical recording medium having dual information surfaces |
| IL118836A (en) | 1996-07-11 | 2001-01-11 | Teva Pharma | Pharmaceutical compositions comprising s-(-)-n-propargyl-1-aminoindan |
| US7129061B1 (en) * | 1996-08-07 | 2006-10-31 | Biogen Idec Ma Inc. | Tumor necrosis factor related ligand |
| GB9715082D0 (en) * | 1997-07-17 | 1997-09-24 | Scherer Ltd R P | Treatment of attention deficit hyperactivity disorder and narcolepsy |
| US6232326B1 (en) | 1998-07-14 | 2001-05-15 | Jodi A. Nelson | Treatment for schizophrenia and other dopamine system dysfunctions |
| JP2003512426A (ja) | 1999-10-27 | 2003-04-02 | テバ ファーマシューティカル インダストリーズ リミティド | 双極性気分障害における躁病の治療のための1−アミノインダンの使用。 |
| EP1441708B1 (en) | 2001-11-05 | 2009-04-08 | Krele Pharmaceuticals LLC | Compositions and methods for increasing compliance with therapies using aldehyde dehydrogenase inhibitors and treating alcoholism |
| US20040010038A1 (en) * | 2002-02-27 | 2004-01-15 | Eran Blaugrund | Propargylamino indan derivatives and propargylamino tetralin derivatives as brain-selective MAO inhibitors |
| US8058442B2 (en) * | 2002-11-07 | 2011-11-15 | Technion Research And Development Foundation Ltd. | Neuroprotective iron chelators and pharmaceutical compositions comprising them |
| ES2588780T3 (es) * | 2002-11-15 | 2016-11-04 | Teva Pharmaceutical Industries Limited | Uso de rasagilina con o sin riluzol para el tratamiento de la esclerosis lateral amiotrófica |
| US20040176430A1 (en) * | 2002-11-21 | 2004-09-09 | Jeffrey Sterling | Propargyl-trifluoromethoxy-amino-benzothiazole derivatives |
| CN1605336A (zh) | 2003-10-10 | 2005-04-13 | 中国医学科学院药物研究所 | 左旋丁基苯酞在制备预防和治疗脑梗塞的药物中的应用 |
| JP2007512319A (ja) * | 2003-11-25 | 2007-05-17 | テクニオン リサーチ アンド ディベロップメント ファウンデーション リミテッド | 心臓血管障害及び疾患を治療するための組成物及び方法 |
| US8097608B2 (en) * | 2003-11-25 | 2012-01-17 | Technion Research And Development Foundation Ltd. | Methods for treatment of cardiovascular disorders and diseases |
| JP2005232148A (ja) * | 2004-02-03 | 2005-09-02 | Technion Research & Development Foundation Ltd | 神経保護剤としてプロパルギルアミンの使用 |
| US20050197365A1 (en) * | 2004-02-27 | 2005-09-08 | Jeffrey Sterling | Diamino thiazoloindan derivatives and their use |
| CA2574925A1 (en) * | 2004-07-26 | 2006-02-09 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical dosage forms including rasagiline |
| US20060025446A1 (en) * | 2004-07-27 | 2006-02-02 | Jeffrey Sterling | Propargyl nitroxides and indanyl nitroxides and their use for the treatment of neurologic diseases and disorders |
| WO2006014968A2 (en) * | 2004-07-27 | 2006-02-09 | Teva Pharmaceutical Industries, Ltd. | Propargyl nitroxydes and indanyl nitroxides and their use for the treatment of neurologic diseases and disorders |
| DK1848415T3 (da) * | 2005-02-17 | 2013-07-08 | Teva Pharma | Kombinationsterapi med glatirameracetat og rasagilin til behandling af multipel sklerose |
| DK2332408T3 (da) | 2005-02-17 | 2013-12-02 | Biogen Idec Inc | Behandling af neurologiske sygdomme |
| US20100167983A1 (en) * | 2007-10-22 | 2010-07-01 | Teva Pharmaceutical Industries, Ltd. | Combination therapy with glatiramer acetate and rasagiline for the treatment of multiple sclerosis |
| KR20170023211A (ko) * | 2005-02-23 | 2017-03-02 | 테바 파마슈티컬 인더스트리즈 리미티드 | 함량 균일성이 개선된 라사길린 제형 |
| AU2006216509B8 (en) * | 2005-02-24 | 2012-11-01 | Technion Research And Development Foundation Ltd | Formulations of ladostigil tartrate |
| CA2607697C (en) | 2005-05-10 | 2015-01-06 | Biogen Idec Ma Inc. | Treating and evaluating inflammatory disorders |
| EP1888056A4 (en) * | 2005-06-01 | 2008-09-03 | Teva Pharma | USE OF LADOSTIGIL FOR TREATING MULTIPLE SCLEROSIS |
| FR2886549B1 (fr) * | 2005-06-06 | 2007-09-07 | Biocodex | Composition pharmaceutique destinee a la prevention ou au traitement des oedemes cerebraux |
| US8263655B2 (en) * | 2005-10-06 | 2012-09-11 | Technion Research And Development Foundation Ltd | Methods for treatment of renal failure |
| WO2007061717A2 (en) * | 2005-11-17 | 2007-05-31 | Teva Pharmaceutical Industries, Ltd. | Methods for isolating propargylated aminoindans |
| US7572834B1 (en) | 2005-12-06 | 2009-08-11 | Teva Pharmaceutical Industries, Ltd. | Rasagiline formulations and processes for their preparation |
| CN103142570A (zh) * | 2005-12-09 | 2013-06-12 | 耶路撒冷希伯来大学伊森姆研究发展公司 | 低剂量Ladostigil 用于神经保护的用途 |
| US20070135518A1 (en) * | 2005-12-09 | 2007-06-14 | Marta Weinstock-Rosin | Use of low-dose ladostigil for neuroprotection |
| US20110047685A1 (en) * | 2006-02-16 | 2011-03-03 | Ferrara Vincent R | Impact energy management method and system |
| AU2007217349B9 (en) | 2006-02-21 | 2013-06-27 | Teva Pharmaceutical Industries, Ltd. | Use of rasagiline for the treatment of Multiple System Atrophy |
| TW200744576A (en) * | 2006-02-24 | 2007-12-16 | Teva Pharma | Propargylated aminoindans, processes for preparation, and uses thereof |
| JP5769923B2 (ja) * | 2006-04-03 | 2015-08-26 | テバ ファーマシューティカル インダストリーズ リミティド | レストレスレッグス症候群の治療のためのラサギリンの使用 |
| CN101062897B (zh) * | 2006-04-25 | 2011-11-23 | 重庆医药工业研究院有限责任公司 | 一种制备2,3-二氢-1h-茚-1-胺及其衍生物的改进方法 |
| EP1892233A1 (de) * | 2006-08-18 | 2008-02-27 | Ratiopharm GmbH | Neue Salze des Wirkstoffs Rasagilin |
| ATE528989T1 (de) * | 2006-12-14 | 2011-11-15 | Teva Pharma | Kristalline feste rasagilin-base |
| CN101600346B (zh) * | 2006-12-14 | 2013-08-21 | 泰华制药工业有限公司 | 雷沙吉兰的单宁酸盐 |
| EP1987816A1 (de) * | 2007-04-30 | 2008-11-05 | Ratiopharm GmbH | Adsorbate eines Rasagilinsalzes mit einem wasserlöslichen Hilfsstoff |
| WO2009032273A1 (en) * | 2007-09-05 | 2009-03-12 | Teva Pharmaceutical Industries, Ltd. | Method of treating glaucoma using rasagiline |
| US8188149B2 (en) * | 2007-09-17 | 2012-05-29 | Teva Pharmaceutical Industries, Ltd. | Use of R(+)-N-propargy1-1-aminoindan to treat or prevent hearing loss |
| BRPI0905680A2 (pt) * | 2008-01-11 | 2015-07-07 | Teva Pharma | "composição farmacêutica de uma composição farmacêutica" |
| US20110105788A1 (en) * | 2008-03-28 | 2011-05-05 | Medichem, S.A. | Polymorphic Form of an Aminoindan Mesylate Derivative |
| CA2723870C (en) * | 2008-06-02 | 2015-04-21 | Generics [Uk] Limited | An improved process for the preparation of amines |
| CN102123980B (zh) | 2008-06-02 | 2014-05-07 | 基因里克斯(英国)有限公司 | 用于制备对映异构纯胺的方法 |
| US20100008983A1 (en) * | 2008-06-10 | 2010-01-14 | Muhammad Safadi | Rasagiline soft gelatin capsules |
| AU2009258151A1 (en) * | 2008-06-13 | 2009-12-17 | Teva Pharmaceutical Industries, Ltd. | Rasagiline for Parkinson's disease modification |
| EA021472B1 (ru) * | 2008-06-19 | 2015-06-30 | Тева Фармасьютикал Индастриз, Лтд. | Способ получения и сушки твердого разагилина в форме основания |
| AU2009260733B2 (en) * | 2008-06-19 | 2015-01-29 | Teva Pharmaceutical Industries, Ltd. | Process for purifying rasagiline base |
| WO2011012140A2 (en) | 2008-07-11 | 2011-02-03 | Synthon Bv | Polymorphs of rasagiline hydrochloride |
| US20110263719A1 (en) * | 2008-07-30 | 2011-10-27 | Vinayak Gore | Polymorphic form of rasagiline mesylate |
| US20100189791A1 (en) * | 2009-01-23 | 2010-07-29 | Teva Pharmaceutical Industries, Ltd. | Delayed release rasagiline malate formulation |
| EP2218444A3 (en) | 2009-01-23 | 2010-08-25 | Teva Pharmaceutical Industries, Ltd. | Delayed release rasagiline formulation |
| US8633237B2 (en) * | 2009-04-09 | 2014-01-21 | Merck Sharp & Dohme B.V. | Indane derivatives |
| JP2012532843A (ja) | 2009-07-09 | 2012-12-20 | ラティオファーム ゲーエムベーハー | ラサギリンの塩およびその製剤 |
| CN102048717B (zh) † | 2009-10-29 | 2014-02-19 | 重庆医药工业研究院有限责任公司 | 一种稳定的雷沙吉兰组合物 |
| EP2325159A1 (en) | 2009-11-24 | 2011-05-25 | LEK Pharmaceuticals d.d. | Novel salts of rasagiline |
| US8741962B2 (en) * | 2009-11-26 | 2014-06-03 | Usv Limited | Process for preparation of Rasagiline and salts thereof |
| WO2011087791A1 (en) * | 2009-12-22 | 2011-07-21 | Teva Pharmaceutical Industries Ltd. | 3-keto-n-propargyl-1-aminoindan |
| CA2789006C (en) | 2010-02-03 | 2018-11-27 | Pharma Two B Ltd. | Extended release formulations of rasagiline and uses thereof |
| US9017723B2 (en) | 2010-04-30 | 2015-04-28 | Teikoku Pharma Usa, Inc. | Propynylaminoindan transdermal compositions |
| JP2013533287A (ja) | 2010-07-27 | 2013-08-22 | テバ ファーマシューティカル インダストリーズ リミティド | 嗅覚機能不全の処置のためのラサギリンの使用 |
| WO2012015946A1 (en) | 2010-07-27 | 2012-02-02 | Teva Pharmaceutical Industries Ltd. | Dispersion of rasagiline citrate |
| JP6355921B2 (ja) | 2010-09-01 | 2018-07-11 | トニックス ファーマスーティカルズ, インコーポレイテッドTONIX Pharmaceuticals, Inc. | コカイン嗜癖の治療 |
| SG189454A1 (en) | 2010-10-26 | 2013-05-31 | Teva Pharma | Deuterium enriched rasagiline |
| WO2012125020A1 (en) * | 2011-03-14 | 2012-09-20 | N.V. Nutricia | Method for treating neurotrauma |
| EP2688561B1 (en) | 2011-03-24 | 2018-08-22 | Teikoku Pharma USA, Inc. | Transdermal compositions comprising an active agent layer and an active agent conversion layer |
| JP2014534197A (ja) | 2011-10-10 | 2014-12-18 | テバ ファーマシューティカル インダストリーズ リミティド | R(+)−n−メチル−プロパルギルアミノインダン |
| HK1200315A1 (en) | 2011-10-10 | 2015-08-07 | Teva Pharmaceutical Industries Ltd. | R(+)-n-formyl-propargyl-aminoindan |
| JP5913614B2 (ja) | 2011-11-09 | 2016-04-27 | テイコク ファーマ ユーエスエー インコーポレーテッド | 皮膚新生物の処置方法 |
| MX343986B (es) | 2012-03-21 | 2016-12-01 | Synthon Bv | Composiciones farmaceuticas estabilizadas que comprenden sales de rasagilina. |
| WO2013175493A1 (en) | 2012-04-09 | 2013-11-28 | Cadila Healthcare Limited | Stable oral pharmaceutical compositions |
| WO2014028868A1 (en) | 2012-08-17 | 2014-02-20 | Teva Pharmaceutical Industries Ltd. | Parenteral formulation of rasagiline |
| KR101856515B1 (ko) | 2012-11-02 | 2018-05-10 | 테이코쿠 팔마 유에스에이, 인코포레이티드 | 프로피닐아미노인단 경피 조성물 |
| ES2502140T1 (es) * | 2013-02-06 | 2014-10-02 | Galenicum Health S.L. | Comprimidos de liberación inmediata de rasagilina hemitartrato |
| EP2796130A3 (en) * | 2013-02-06 | 2015-02-25 | Galenicum Health S.L. | Immediate release tablets of rasagiline hemitartrate |
| JP2016512231A (ja) * | 2013-03-13 | 2016-04-25 | エヌ ティーオー ビー リミテッドN To B Ltd. | パーキンソン病に伴う運動及び抑うつ症状の治療方法、組成物及び装置 |
| CN103804200B (zh) * | 2014-02-21 | 2015-04-29 | 常州市第四制药厂有限公司 | 雷沙吉兰及其类似物的制备方法 |
| WO2020214886A1 (en) * | 2019-04-17 | 2020-10-22 | Vici Health Sciences LLC | Liquid pharmaceutical compositions |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1003686A (en) | 1962-06-19 | 1965-09-08 | Ciba Ltd | Unsaturated amines |
| GB1037014A (en) | 1963-08-02 | 1966-07-20 | Aspro Nicholas Ltd | Derivatives of 1-aminoindane |
| US3513244A (en) | 1966-07-16 | 1970-05-19 | Aspro Nicholas Ltd | Methods of lowering blood pressure in animals by administering secondary and tertiary amines |
| US4826875A (en) | 1986-06-10 | 1989-05-02 | Chiesi Farmaceutici S.P.A. | Pharmaceutical compositions containing levodopa methyl ester, preparation and therapeutic applications thereof |
| EP0436492A2 (en) | 1990-01-03 | 1991-07-10 | Teva Pharmaceutical Industries Limited | R-Enantiomer of N-propargyl-1-aminoindan, its preparation and pharmaceutical compositions containing it |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US513244A (en) * | 1894-01-23 | Island | ||
| US3201470A (en) * | 1965-08-17 | Chsx c cech | ||
| US3513249A (en) * | 1968-12-24 | 1970-05-19 | Ideal Ind | Explosion connector with improved insulating means |
| GB1548022A (en) | 1976-10-06 | 1979-07-04 | Wyeth John & Brother Ltd | Pharmaceutial dosage forms |
| EP0258096B1 (fr) | 1986-08-21 | 1992-09-09 | Roussel-Uclaf | Dérivés de l'indane, leur procédé de préparation, leur application à titre de médicaments, les compositions pharmaceutiques les renfermant et les intermédiaires obtenus |
| HU197510B (en) | 1986-12-19 | 1989-04-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing pharmaceutical composition containing phenyl-alkyl-amine derivatives, against motion-sick |
| US4855326A (en) * | 1987-04-20 | 1989-08-08 | Fuisz Pharmaceutical Ltd. | Rapidly dissoluble medicinal dosage unit and method of manufacture |
| ZA885824B (en) | 1987-08-14 | 1989-04-26 | Merrell Dow Pharma | Novel antidepressants |
| FR2626877B1 (fr) | 1988-02-05 | 1991-04-05 | Delalande Sa | Ethers alkyliques ou benzyliques du phenol, leurs procedes de preparation et leur application en therapeutique |
| HU208484B (en) | 1988-08-17 | 1993-11-29 | Chinoin Gyogyszer Es Vegyeszet | Process for producing pharmaceutical composition containing acid additional salt of selegilin as active component for treating schisofrenia |
| GB8909793D0 (en) | 1989-04-28 | 1989-06-14 | Beecham Group Plc | Pharmaceutical formulation |
| US5079018A (en) * | 1989-08-14 | 1992-01-07 | Neophore Technologies, Inc. | Freeze dry composition and method for oral administration of drugs, biologicals, nutrients and foodstuffs |
| AU648274B2 (en) | 1989-09-25 | 1994-04-21 | United States of America, as represented by the Secretary, U.S. Department of Commerce, The | Evaluative means for detecting inflammatory reactivity and for predicting response to stress |
| EP0737473A1 (en) | 1989-10-02 | 1996-10-16 | Cima Labs, Inc. | Effervescent dosage form |
| FR2655044B1 (fr) | 1989-11-24 | 1995-03-03 | Delalande Sa | Derives d'(hetero) arylmethyloxy-4 phenyl tetrazole et oxadiazole, leur procede de preparation et leur application en therapeutique. |
| JPH03176457A (ja) | 1989-12-04 | 1991-07-31 | Nippon Paint Co Ltd | 新規プロパルギル化合物、その製法ならびに該化合物を含む被覆材 |
| US5744500A (en) | 1990-01-03 | 1998-04-28 | Teva Pharmaceutical Industries, Ltd. | Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof |
| CA2039742A1 (en) | 1990-04-23 | 1991-10-24 | Andrew B. Dennis | Tablet composition and method for problem pharmaceutical materials |
| US5169868A (en) | 1991-03-01 | 1992-12-08 | University Of Saskatchewan | Aliphatic propargylamines as specific mao-b inhibitors |
| US5844003A (en) * | 1991-04-04 | 1998-12-01 | Innovations Foundation | Use of deprenyl compounds to maintain, prevent loss, or recover nerve cell function |
| US5767164A (en) * | 1991-04-04 | 1998-06-16 | Innovations Foundation | Use of deprenyl to rescue damaged nerve cells |
| US5444095A (en) * | 1991-04-04 | 1995-08-22 | University Of Toronto, Innovations Foundation | Use of deprenyl to rescue damaged nerve cells |
| IL99759A (en) | 1991-10-16 | 1997-06-10 | Teva Pharma | Mono-fluorinated derivatives of n-propargyl-1-aminoindan, their preparation and pharmaceutical compositions containing them |
| FI943042L (fi) * | 1991-12-24 | 1994-06-23 | Yamanouchi Pharma Co Ltd | Suuontelossa hajoava valmiste ja sen valmistus |
| US5298261A (en) * | 1992-04-20 | 1994-03-29 | Oregon Freeze Dry, Inc. | Rapidly distintegrating tablet |
| AU4534593A (en) | 1992-06-12 | 1994-01-04 | Affymax Technologies N.V. | Compositions and methods for enhanced drug delivery |
| SE501848C2 (sv) | 1992-11-18 | 1995-06-06 | Kvaerner Pulping Tech | Metod att koka massa kontinuerligt vid konstant temperatur |
| IL111240A (en) | 1993-10-18 | 2001-10-31 | Teva Pharma | Salts of r(+) - enantiomers of n- propargyl-1-aminoindan and pharmaceutical compositions comprising them |
| IL112779A (en) | 1994-03-01 | 1999-11-30 | Gergely Gerhard | Granular product or tablet containing an efferescent system and an active pharmaceutical substance and its preparation |
| DE69628415T3 (de) | 1995-03-02 | 2008-06-26 | R.P. Scherer Technologies, Inc., Paradise Valley | Arzneimittel enthaltend monoaminooxidase-b-hemmer |
| IL115357A (en) | 1995-09-20 | 2000-01-31 | Teva Pharma | Stable compositions containing N-propargyl-1-aminoindan and polyhydric alcohols |
| IL118836A (en) * | 1996-07-11 | 2001-01-11 | Teva Pharma | Pharmaceutical compositions comprising s-(-)-n-propargyl-1-aminoindan |
| WO1999037293A2 (en) * | 1998-01-27 | 1999-07-29 | Thomas Thomas N | Use of an mao-a or mao-b inhibitor for the treatment of vascular disorders |
| FI104042B (fi) * | 1998-09-29 | 1999-11-15 | Aaro Kiuru | Menetelmä keuhkojen perfuusion mittaamiseksi |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| US20030180352A1 (en) * | 1999-11-23 | 2003-09-25 | Patel Mahesh V. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| CA2452738C (en) * | 2001-07-04 | 2011-06-14 | Sun Pharmaceutical Industries Limited | Gastric retention controlled drug delivery system |
| US20040010038A1 (en) * | 2002-02-27 | 2004-01-15 | Eran Blaugrund | Propargylamino indan derivatives and propargylamino tetralin derivatives as brain-selective MAO inhibitors |
| 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 |
| US20060009483A1 (en) * | 2002-05-31 | 2006-01-12 | Bayer Pharmaceuticals Corporation | Compounds and compositions for the treatment of diabetes and diabetes-related disorders |
| WO2004026453A2 (en) * | 2002-09-06 | 2004-04-01 | Genteric, Inc. | Microcapsules and methods of use |
| ES2588780T3 (es) * | 2002-11-15 | 2016-11-04 | Teva Pharmaceutical Industries Limited | Uso de rasagilina con o sin riluzol para el tratamiento de la esclerosis lateral amiotrófica |
| US20050026979A1 (en) * | 2003-07-31 | 2005-02-03 | Maha Ghazzi | Methods for treating inflammation and inflammation-associated diseases with a statin and ether |
| KR20170023211A (ko) * | 2005-02-23 | 2017-03-02 | 테바 파마슈티컬 인더스트리즈 리미티드 | 함량 균일성이 개선된 라사길린 제형 |
-
1995
- 1995-05-22 US US08/446,439 patent/US5744500A/en not_active Expired - Lifetime
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1996
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- 1996-05-22 CN CN96195710A patent/CN1096853C/zh not_active Expired - Fee Related
- 1996-05-22 WO PCT/US1996/007465 patent/WO1996037199A1/en not_active Ceased
- 1996-05-22 BR BR9608733-1A patent/BR9608733A/pt not_active Application Discontinuation
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- 1996-05-22 RU RU97121002/14A patent/RU2203653C2/ru not_active IP Right Cessation
- 1996-05-22 HU HU9901629A patent/HUP9901629A3/hu unknown
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- 1997-12-22 LT LT97-200A patent/LT4455B/lt not_active IP Right Cessation
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- 1998-01-20 LV LVP-97-267A patent/LV12083B/en unknown
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- 2001-10-26 US US10/016,268 patent/US6630514B2/en not_active Expired - Fee Related
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2002
- 2002-11-27 US US10/305,478 patent/US6956060B2/en not_active Expired - Fee Related
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- 2005-06-17 US US11/155,864 patent/US20060094783A1/en not_active Abandoned
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- 2006-11-10 US US11/595,726 patent/US20070100001A1/en not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1003686A (en) | 1962-06-19 | 1965-09-08 | Ciba Ltd | Unsaturated amines |
| GB1037014A (en) | 1963-08-02 | 1966-07-20 | Aspro Nicholas Ltd | Derivatives of 1-aminoindane |
| US3513244A (en) | 1966-07-16 | 1970-05-19 | Aspro Nicholas Ltd | Methods of lowering blood pressure in animals by administering secondary and tertiary amines |
| US4826875A (en) | 1986-06-10 | 1989-05-02 | Chiesi Farmaceutici S.P.A. | Pharmaceutical compositions containing levodopa methyl ester, preparation and therapeutic applications thereof |
| EP0436492A2 (en) | 1990-01-03 | 1991-07-10 | Teva Pharmaceutical Industries Limited | R-Enantiomer of N-propargyl-1-aminoindan, its preparation and pharmaceutical compositions containing it |
Non-Patent Citations (3)
| Title |
|---|
| KNOLL J, MAGYAR K.: "Some puzzling pharmacological effects of monoamine oxidase inhibitors", ADV BIOCHEM PSYCHOHARMACOL, 1972, pages 393 - 408 |
| KNOLL J, MAGYAR K.: "Some puzzling pharmacological effects of monoamine oxidase inhibitors", ADV BIOCHEM PSYCHOPHARMACOL., 1972, pages 393 - 408 |
| YOUDIM ET AL.: "Handbook of Experimental Pharmacology" |
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