NO328959B1 - Stabiliserte farmasoytiske preparater av gamma-aminosmorsyrederivater og fremgangsmate for fremstilling av disse - Google Patents
Stabiliserte farmasoytiske preparater av gamma-aminosmorsyrederivater og fremgangsmate for fremstilling av disse Download PDFInfo
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- NO328959B1 NO328959B1 NO20005768A NO20005768A NO328959B1 NO 328959 B1 NO328959 B1 NO 328959B1 NO 20005768 A NO20005768 A NO 20005768A NO 20005768 A NO20005768 A NO 20005768A NO 328959 B1 NO328959 B1 NO 328959B1
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polymerisation Methods In General (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13311398 | 1998-05-15 | ||
| PCT/US1999/010190 WO1999059573A1 (fr) | 1998-05-15 | 1999-05-10 | Preparations pharmaceutiques stabilisees de derives d'acide gamma-aminobutyrique et procede de fabrication associe |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20005768L NO20005768L (no) | 2000-11-14 |
| NO20005768D0 NO20005768D0 (no) | 2000-11-14 |
| NO328959B1 true NO328959B1 (no) | 2010-06-28 |
Family
ID=15097118
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20005768A NO328959B1 (no) | 1998-05-15 | 2000-11-14 | Stabiliserte farmasoytiske preparater av gamma-aminosmorsyrederivater og fremgangsmate for fremstilling av disse |
Country Status (37)
| Country | Link |
|---|---|
| US (1) | US7309719B1 (fr) |
| EP (1) | EP1077692B1 (fr) |
| JP (1) | JP4612923B2 (fr) |
| KR (1) | KR100602047B1 (fr) |
| CN (1) | CN1303991C (fr) |
| AR (1) | AR020323A1 (fr) |
| AT (1) | ATE271864T1 (fr) |
| AU (1) | AU768277B2 (fr) |
| BR (1) | BR9910508B1 (fr) |
| CA (1) | CA2327285C (fr) |
| CO (1) | CO5021224A1 (fr) |
| CR (1) | CR6026A (fr) |
| CU (1) | CU23253B7 (fr) |
| DE (1) | DE69918977T2 (fr) |
| DK (1) | DK1077692T3 (fr) |
| EG (1) | EG26803A (fr) |
| ES (1) | ES2221385T3 (fr) |
| GT (1) | GT199900069A (fr) |
| HK (1) | HK1036586A1 (fr) |
| HN (1) | HN1999000072A (fr) |
| HU (1) | HU228771B1 (fr) |
| ID (1) | ID27724A (fr) |
| IL (2) | IL139298A0 (fr) |
| IS (1) | IS2233B (fr) |
| MY (1) | MY157878A (fr) |
| NO (1) | NO328959B1 (fr) |
| NZ (1) | NZ508015A (fr) |
| PA (1) | PA8472801A1 (fr) |
| PE (1) | PE20000556A1 (fr) |
| PL (1) | PL204921B1 (fr) |
| PT (1) | PT1077692E (fr) |
| SI (1) | SI1077692T1 (fr) |
| SV (1) | SV1999000064A (fr) |
| TW (1) | TWI243054B (fr) |
| UY (1) | UY25512A1 (fr) |
| WO (1) | WO1999059573A1 (fr) |
| ZA (1) | ZA200006484B (fr) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE41920E1 (en) | 1996-07-24 | 2010-11-09 | Warner-Lambert Company Llc | Isobutylgaba and its derivatives for the treatment of pain |
| EP1430893A1 (fr) * | 2000-06-16 | 2004-06-23 | Teva Pharmaceutical Industries Ltd. | Gabapentin stable contenant plus de 20 ppm d'ions chlore |
| EP1384473A1 (fr) * | 2000-06-16 | 2004-01-28 | Teva Pharmaceutical Industries Ltd. | Gabapentin stable contenant plus de 20 ppm d'ions chlore |
| JP2003535885A (ja) * | 2000-06-16 | 2003-12-02 | 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 | 制御された範囲内にｐＨを持つ安定なギャバペンチン |
| US6531509B2 (en) * | 2000-06-16 | 2003-03-11 | Teva Pharmaceutical Industries Ltd. | Stable gabapentin containing more than 20 ppm of chlorine ion |
| US7056951B2 (en) | 2000-09-26 | 2006-06-06 | Mutual Pharmaceutical Co., Inc. | Stable solid dosage forms of amino acids and processes for producing same |
| CZ299755B6 (cs) * | 2001-05-25 | 2008-11-12 | Warner-Lambert Company Llc | Kapalná farmaceutická kompozice obsahující analoggama-aminomáselné kyseliny, zpusob její prípravy a použití |
| WO2005074895A1 (fr) * | 2004-02-04 | 2005-08-18 | Alembic Limited | Micro-comprimes revetus a liberation prolongee de chlorhydrate de venlafaxine |
| JP2007538080A (ja) * | 2004-05-17 | 2007-12-27 | オデッサ ファーマ，エルエルシー | α−ケト分岐鎖アミノ酸を用いた脳神経細胞内グルタミン酸レベルの低減 |
| NL2000281C2 (nl) | 2005-11-02 | 2007-08-07 | Pfizer Prod Inc | Vaste farmaceutische samenstellingen die pregabaline bevatten. |
| WO2007107835A2 (fr) * | 2006-03-17 | 2007-09-27 | Aurobindo Pharma Limited | Formulations liquides stables d'agents anti-epileptiques |
| DE102007019071A1 (de) | 2007-04-23 | 2008-10-30 | Ratiopharm Gmbh | Stabilisierte pharmazeutische Zusammensetzung enthaltend Pregabalin |
| FR2918567B1 (fr) * | 2007-07-11 | 2012-08-03 | Pf Medicament | Composition pharmaceutique stable d'un sel hydrosoluble de vinorelbine. |
| EP2116618A1 (fr) | 2008-05-09 | 2009-11-11 | Agency for Science, Technology And Research | Diagnostic et traitement de la maladie de Kawasaki |
| JP5643297B2 (ja) * | 2009-05-19 | 2014-12-17 | ニューロデルム リミテッド | ドーパデカルボキシラーゼ阻害剤の連続投与のための組成物 |
| HU230031B1 (hu) | 2010-03-01 | 2015-05-28 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Pregabalint és izomaltot tartalmazó stabilizált gyógyszerkészítmény |
| EP2389934A1 (fr) | 2010-05-25 | 2011-11-30 | Sanovel Ilac Sanayi ve Ticaret A.S. | Formulations de prégabaline en comprimé à libération prolongée |
| EP2389933A1 (fr) | 2010-05-25 | 2011-11-30 | Sanovel Ilac Sanayi ve Ticaret A.S. | Compositions comprenant de la prégabaline à libération contrôlée |
| TR201005241A1 (tr) | 2010-05-25 | 2012-01-23 | Sanovel �La� San. Ve T�C. A.�. | Kontrollü salım sağlayan pregabalin solüsyon formülasyonu. |
| ES2660772T3 (es) | 2010-11-15 | 2018-03-26 | Neuroderm Ltd | Administración continua de L-dopa, inhibidores de dopa descarboxilasa, inhibidores de catecol-o-metil transferasa y composiciones para ello |
| CN107693486A (zh) | 2012-06-05 | 2018-02-16 | 纽罗德姆有限公司 | 包含阿朴吗啡和有机酸的组合物及其用途 |
| CN103494796B (zh) * | 2013-09-30 | 2016-01-20 | 浙江华义医药有限公司 | 普瑞巴林稳定的药物组合物及其制备方法 |
| EP3099288A1 (fr) | 2014-01-28 | 2016-12-07 | Sun Pharmaceutical Industries Ltd | Comprimés à rétention gastrique stabilisée de prégabaline |
| EP3777833B1 (fr) | 2014-03-13 | 2023-10-18 | Neuroderm Ltd. | Compositions d'inhibiteurs de dopa-décarboxylase |
| US10258585B2 (en) | 2014-03-13 | 2019-04-16 | Neuroderm, Ltd. | DOPA decarboxylase inhibitor compositions |
| WO2015144825A1 (fr) * | 2014-03-27 | 2015-10-01 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Solution pharmaceutique liquide orale de gabapentine |
| MA39272A (fr) * | 2014-04-09 | 2015-10-14 | Arven Ilac Sanayi Ve Ticaret As | Formulations à libération prolongée de gabapentine |
| JP2018520112A (ja) | 2015-05-26 | 2018-07-26 | オディディ，イサ | 制御持続放出プレガバリン |
| JP6919119B2 (ja) * | 2017-01-23 | 2021-08-18 | 日新製薬株式会社 | ３位が置換されたγ−アミノ酪酸誘導体を含有する圧縮固形医薬組成物。 |
| WO2020071546A1 (fr) | 2018-10-04 | 2020-04-09 | 株式会社 メドレックス | Préparation stabilisée au moyen d'un solvant non aqueux |
| US11654124B2 (en) | 2019-07-29 | 2023-05-23 | Amneal Pharmaceuticals Llc | Stabilized formulations of 4-amino-3-substituted butanoic acid derivatives |
| US10792262B1 (en) * | 2019-07-29 | 2020-10-06 | Saol International Limited | Stabilized formulations of 4-amino-3-substituted butanoic acid derivatives |
| WO2021079887A1 (fr) | 2019-10-25 | 2021-04-29 | 国立大学法人京都大学 | Agent thérapeutique ou de prévention d'une tauopathie |
| US11844754B2 (en) | 2020-11-17 | 2023-12-19 | Neuroderm, Ltd. | Methods for treatment of Parkinson's disease |
| US11331293B1 (en) | 2020-11-17 | 2022-05-17 | Neuroderm, Ltd. | Method for treatment of Parkinson's disease |
| US11213502B1 (en) | 2020-11-17 | 2022-01-04 | Neuroderm, Ltd. | Method for treatment of parkinson's disease |
| CN112843015A (zh) * | 2021-04-08 | 2021-05-28 | 海南鑫开源医药科技有限公司 | 一种加巴喷丁胶囊制剂及其制备方法 |
| WO2023055457A1 (fr) | 2021-09-29 | 2023-04-06 | Amneal Pharmaceuticals Llc | Formulations en granules contenant du baclofène et réduction des variations de l'exposition du patient aux métabolites |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4087544A (en) | 1974-12-21 | 1978-05-02 | Warner-Lambert Company | Treatment of cranial dysfunctions using novel cyclic amino acids |
| DE2460891C2 (de) | 1974-12-21 | 1982-09-23 | Gödecke AG, 1000 Berlin | 1-Aminomethyl-1-cycloalkanessigsäuren und deren Ester, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| US4126684A (en) * | 1976-02-11 | 1978-11-21 | Ciba-Geigy Corporation | 4-amino-3-p-halophenylbutyric acids and their derivatives used in the control of narcotic abuse |
| US4255448A (en) * | 1979-09-10 | 1981-03-10 | Wisconsin Alumni Research Foundation | Method for reducing epileptiform activity |
| GB8311804D0 (en) * | 1983-04-29 | 1983-06-02 | Merrell Toraude & Co | Treatment of seizure disorders and pharmaceutical compositions |
| US4595697A (en) * | 1984-03-28 | 1986-06-17 | Merrell Dow Pharmaceuticals Inc. | Treatment of seizure disorders and pharmaceutical compositions useful therein |
| CA1249968A (fr) * | 1984-04-05 | 1989-02-14 | Kazuo Kigasawa | Base pour baume |
| JPS63253022A (ja) * | 1987-04-08 | 1988-10-20 | Nitto Electric Ind Co Ltd | バクロフエン外用製剤 |
| PH26730A (en) * | 1988-12-30 | 1992-09-28 | Ciba Geigy Ag | Coated adhesive tablets |
| DE3928183A1 (de) * | 1989-08-25 | 1991-02-28 | Goedecke Ag | Lactamfreie cyclische aminosaeuren |
| US5006560A (en) * | 1989-12-20 | 1991-04-09 | Schering Corporation | Use of GABA-B selective agonists as anti-tussive agents |
| US5084479A (en) * | 1990-01-02 | 1992-01-28 | Warner-Lambert Company | Novel methods for treating neurodegenerative diseases |
| EP0458751A1 (fr) | 1990-05-25 | 1991-11-27 | Warner-Lambert Company | Système à libération d'amino-acides cycliques avec gôut, texture et compressibilité améliorés |
| US5025035A (en) | 1990-10-12 | 1991-06-18 | Warner-Lambert Company | Method of treating depression |
| GB9023585D0 (en) * | 1990-10-30 | 1990-12-12 | Beecham Group Plc | Novel compounds |
| HUT59656A (en) * | 1990-11-15 | 1992-06-29 | Puetter Medice Chem Pharm | Process for producing s/+/-phenyl-alkanoic acids and alpha-amino-acids containing complexes and pharmaceutical compositions containing them as active components |
| US6197819B1 (en) * | 1990-11-27 | 2001-03-06 | Northwestern University | Gamma amino butyric acid analogs and optical isomers |
| JPH0597703A (ja) * | 1991-10-04 | 1993-04-20 | Yamanouchi Pharmaceut Co Ltd | 改変型組織プラスミノーゲン活性化因子含有組成物 |
| CA2134674C (fr) * | 1992-05-20 | 2004-12-21 | Richard B. Silverman | Analogues de gaba et de l'acide l-glutamique pour le traitement des convulsions |
| US5629008A (en) * | 1992-06-02 | 1997-05-13 | C.R. Bard, Inc. | Method and device for long-term delivery of drugs |
| US5792451A (en) * | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
| US5248678A (en) * | 1992-06-30 | 1993-09-28 | Fractal Laboratories, Inc. | Methods for increasing arousal and alertness and for the amelioration of comatose states |
| US5260337A (en) * | 1992-07-29 | 1993-11-09 | Merck & Co., Inc. | Ibuprofen-muscle relaxant combinations |
| JP3467794B2 (ja) * | 1993-03-09 | 2003-11-17 | 日本油脂株式会社 | 学習能向上剤 |
| ZA953078B (en) * | 1994-04-28 | 1996-01-05 | Alza Corp | Effective therapy for epilepsies |
| JPH0867636A (ja) * | 1994-08-30 | 1996-03-12 | Yamanouchi Pharmaceut Co Ltd | 播種性血管内凝固症候群（ｄｉｃ）の予防治療薬 |
| GB9420784D0 (en) * | 1994-10-14 | 1994-11-30 | Glaxo Group Ltd | Medicaments |
| US5641512A (en) * | 1995-03-29 | 1997-06-24 | The Procter & Gamble Company | Soft gelatin capsule compositions |
| US5510381A (en) | 1995-05-15 | 1996-04-23 | Warner-Lambert Company | Method of treatment of mania and bipolar disorder |
| JPH1017476A (ja) * | 1996-06-28 | 1998-01-20 | Nippon Seiyaku Kk | 敗血症用非経口製剤及びそれによる予防及び治療方法 |
| AU735389B2 (en) * | 1996-07-22 | 2001-07-05 | Cognetix, Inc. | Use of conantokins |
| USRE41920E1 (en) * | 1996-07-24 | 2010-11-09 | Warner-Lambert Company Llc | Isobutylgaba and its derivatives for the treatment of pain |
| US5780431A (en) * | 1996-09-20 | 1998-07-14 | Neurobiological Technologies, Inc. | Pharmaceutical formulations of corticotropin releasing factor having improved stability in liquid form |
| US6028102A (en) * | 1998-02-24 | 2000-02-22 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Anticonvulsant drugs and pharmaceutical compositions thereof |
| IT1311984B1 (it) * | 1999-03-26 | 2002-03-22 | Bioindustria Lab Italiano Medi | Procedimento per la preparzione di gabapentin. |
| US6383471B1 (en) * | 1999-04-06 | 2002-05-07 | Lipocine, Inc. | Compositions and methods for improved delivery of ionizable hydrophobic therapeutic agents |
| US7056951B2 (en) * | 2000-09-26 | 2006-06-06 | Mutual Pharmaceutical Co., Inc. | Stable solid dosage forms of amino acids and processes for producing same |
| US6979462B1 (en) * | 2000-10-03 | 2005-12-27 | Mutual Pharmaceutical Co., Inc. | Stabilization of solid drug formulations |
| EP1404324B2 (fr) * | 2001-06-11 | 2011-04-06 | XenoPort, Inc. | Promedicaments d'analogues de gaba, compositions et utilisations desdits promedicaments |
-
1999
- 1999-05-10 HU HU0102022A patent/HU228771B1/hu not_active IP Right Cessation
- 1999-05-10 BR BRPI9910508-0A patent/BR9910508B1/pt not_active IP Right Cessation
- 1999-05-10 CN CNB998061557A patent/CN1303991C/zh not_active Expired - Fee Related
- 1999-05-10 US US09/674,815 patent/US7309719B1/en not_active Expired - Fee Related
- 1999-05-10 IL IL13929899A patent/IL139298A0/xx unknown
- 1999-05-10 PL PL344218A patent/PL204921B1/pl unknown
- 1999-05-10 KR KR1020007012759A patent/KR100602047B1/ko not_active IP Right Cessation
- 1999-05-10 EP EP99924166A patent/EP1077692B1/fr not_active Expired - Lifetime
- 1999-05-10 ES ES99924166T patent/ES2221385T3/es not_active Expired - Lifetime
- 1999-05-10 DE DE69918977T patent/DE69918977T2/de not_active Expired - Lifetime
- 1999-05-10 AT AT99924166T patent/ATE271864T1/de active
- 1999-05-10 NZ NZ508015A patent/NZ508015A/en not_active IP Right Cessation
- 1999-05-10 DK DK99924166T patent/DK1077692T3/da active
- 1999-05-10 ID IDW20002352A patent/ID27724A/id unknown
- 1999-05-10 PT PT99924166T patent/PT1077692E/pt unknown
- 1999-05-10 CA CA002327285A patent/CA2327285C/fr not_active Expired - Lifetime
- 1999-05-10 AU AU40735/99A patent/AU768277B2/en not_active Ceased
- 1999-05-10 SI SI9930624T patent/SI1077692T1/xx unknown
- 1999-05-10 WO PCT/US1999/010190 patent/WO1999059573A1/fr active IP Right Grant
- 1999-05-12 TW TW088107704A patent/TWI243054B/zh not_active IP Right Cessation
- 1999-05-12 CR CR6026A patent/CR6026A/es unknown
- 1999-05-13 PA PA19998472801A patent/PA8472801A1/es unknown
- 1999-05-13 MY MYPI99001901A patent/MY157878A/en unknown
- 1999-05-13 EG EG1999050554A patent/EG26803A/en active
- 1999-05-14 JP JP13377399A patent/JP4612923B2/ja not_active Expired - Lifetime
- 1999-05-14 PE PE1999000407A patent/PE20000556A1/es not_active Application Discontinuation
- 1999-05-14 CO CO99030149A patent/CO5021224A1/es unknown
- 1999-05-14 GT GT199900069A patent/GT199900069A/es unknown
- 1999-05-14 SV SV1999000064A patent/SV1999000064A/es active IP Right Grant
- 1999-05-14 UY UY25512A patent/UY25512A1/es not_active IP Right Cessation
- 1999-05-14 HN HN1999000072A patent/HN1999000072A/es unknown
- 1999-05-14 AR ARP990102313A patent/AR020323A1/es active IP Right Grant
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2000
- 2000-10-16 IS IS5666A patent/IS2233B/is unknown
- 2000-10-26 IL IL139298A patent/IL139298A/en not_active IP Right Cessation
- 2000-11-09 ZA ZA200006484A patent/ZA200006484B/en unknown
- 2000-11-14 NO NO20005768A patent/NO328959B1/no not_active IP Right Cessation
- 2000-11-15 CU CU20000256A patent/CU23253B7/es unknown
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2001
- 2001-10-18 HK HK01107298A patent/HK1036586A1/xx not_active IP Right Cessation
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