HUE034890T2 - Malononitrilaminok alkalmazása neuropathiás fájdalomban - Google Patents
Malononitrilaminok alkalmazása neuropathiás fájdalomban Download PDFInfo
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- HUE034890T2 HUE034890T2 HUE11784418A HUE11784418A HUE034890T2 HU E034890 T2 HUE034890 T2 HU E034890T2 HU E11784418 A HUE11784418 A HU E11784418A HU E11784418 A HUE11784418 A HU E11784418A HU E034890 T2 HUE034890 T2 HU E034890T2
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- syndrome
- pain
- neuropathic pain
- neuropathic
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Landscapes
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| WO2018054357A1 (zh) * | 2016-09-24 | 2018-03-29 | 山东亨利医药科技有限责任公司 | 含盐皮质激素受体拮抗剂的药物组合物及其用途 |
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| US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
| IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
| US5073543A (en) | 1988-07-21 | 1991-12-17 | G. D. Searle & Co. | Controlled release formulations of trophic factors in ganglioside-lipsome vehicle |
| IT1229203B (it) | 1989-03-22 | 1991-07-25 | Bioresearch Spa | Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative. |
| US5120548A (en) | 1989-11-07 | 1992-06-09 | Merck & Co., Inc. | Swelling modulated polymeric drug delivery device |
| KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| US5733566A (en) | 1990-05-15 | 1998-03-31 | Alkermes Controlled Therapeutics Inc. Ii | Controlled release of antiparasitic agents in animals |
| AU649421B2 (en) | 1990-05-18 | 1994-05-26 | Sanofi-Aventis Deutschland Gmbh | Isoxazole-4-carboxamides and hydroxyalkylidene-cyanoacetamides, drugs containing these compounds and use of such drugs |
| US5580578A (en) | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
| GB9200275D0 (en) | 1992-01-08 | 1992-02-26 | Roussel Lab Ltd | Chemical compounds |
| US5591767A (en) | 1993-01-25 | 1997-01-07 | Pharmetrix Corporation | Liquid reservoir transdermal patch for the administration of ketorolac |
| IT1270594B (it) | 1994-07-07 | 1997-05-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida |
| FR2727628B1 (fr) * | 1994-12-02 | 1997-01-10 | Roussel Uclaf | Application des derives de 3-cycloalkyl-propanamide a titre de medicaments analgesiques |
| US6566395B1 (en) * | 1999-05-25 | 2003-05-20 | Biomedicines, Inc. | Methods of treating proliferative disorders |
| GB0123571D0 (en) * | 2001-04-05 | 2001-11-21 | Aventis Pharm Prod Inc | Use of (Z)-2-cyano-3-hydroxy-but-2-enoic acid-(4'-trifluoromethylphenyl)-amide for treating multiple sclerosis |
| WO2012025217A1 (en) * | 2010-08-24 | 2012-03-01 | Algiax Pharmaceuticals Gmbh | Novel use of leflunomide and malononitrilamides |
-
2011
- 2011-10-28 HU HUE11784418A patent/HUE034890T2/hu unknown
- 2011-10-28 WO PCT/EP2011/005452 patent/WO2012055567A2/en not_active Ceased
- 2011-10-28 LT LTEP11784418.3T patent/LT2632451T/lt unknown
- 2011-10-28 SI SI201131372T patent/SI2632451T1/en unknown
- 2011-10-28 JP JP2013535311A patent/JP6257326B2/ja active Active
- 2011-10-28 NO NO11784418A patent/NO2632451T3/no unknown
- 2011-10-28 DK DK11784418.3T patent/DK2632451T3/en active
- 2011-10-28 ES ES11784418.3T patent/ES2655084T3/es active Active
- 2011-10-28 RS RS20171305A patent/RS56713B1/sr unknown
- 2011-10-28 EP EP11784418.3A patent/EP2632451B1/en active Active
- 2011-10-28 US US13/880,139 patent/US20130217737A1/en not_active Abandoned
- 2011-10-28 PT PT117844183T patent/PT2632451T/pt unknown
- 2011-10-28 PL PL11784418T patent/PL2632451T3/pl unknown
- 2011-10-28 HR HRP20171848TT patent/HRP20171848T1/hr unknown
- 2011-10-28 CN CN201180051334.6A patent/CN103179962B/zh active Active
- 2011-10-28 CA CA2814371A patent/CA2814371C/en active Active
-
2014
- 2014-07-10 US US14/328,035 patent/US9468615B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CA2814371A1 (en) | 2012-05-03 |
| CN103179962B (zh) | 2017-03-22 |
| DK2632451T3 (en) | 2017-12-18 |
| WO2012055567A2 (en) | 2012-05-03 |
| PT2632451T (pt) | 2017-12-14 |
| EP2632451A2 (en) | 2013-09-04 |
| WO2012055567A3 (en) | 2012-07-05 |
| NO2632451T3 (enExample) | 2018-03-17 |
| CA2814371C (en) | 2019-03-19 |
| US20140357722A1 (en) | 2014-12-04 |
| RS56713B1 (sr) | 2018-03-30 |
| US9468615B2 (en) | 2016-10-18 |
| US20130217737A1 (en) | 2013-08-22 |
| JP2013545730A (ja) | 2013-12-26 |
| ES2655084T3 (es) | 2018-02-16 |
| SI2632451T1 (en) | 2018-02-28 |
| JP6257326B2 (ja) | 2018-01-10 |
| PL2632451T3 (pl) | 2018-04-30 |
| LT2632451T (lt) | 2018-02-12 |
| CN103179962A (zh) | 2013-06-26 |
| EP2632451B1 (en) | 2017-10-18 |
| HRP20171848T1 (hr) | 2018-02-09 |
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