UY27044A1 - Combinación de agonistas de gaba e inhibidores de aldosa-reductasa - Google Patents
Combinación de agonistas de gaba e inhibidores de aldosa-reductasaInfo
- Publication number
- UY27044A1 UY27044A1 UY27044A UY27044A UY27044A1 UY 27044 A1 UY27044 A1 UY 27044A1 UY 27044 A UY27044 A UY 27044A UY 27044 A UY27044 A UY 27044A UY 27044 A1 UY27044 A1 UY 27044A1
- Authority
- UY
- Uruguay
- Prior art keywords
- prodrug
- diabetic
- combinations
- aldosa
- reductasa
- Prior art date
Links
- 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 title abstract 3
- 239000003112 inhibitor Substances 0.000 title 1
- 239000000651 prodrug Substances 0.000 abstract 4
- 229940002612 prodrug Drugs 0.000 abstract 4
- 150000003839 salts Chemical class 0.000 abstract 2
- 208000031229 Cardiomyopathies Diseases 0.000 abstract 1
- 206010007749 Cataract diabetic Diseases 0.000 abstract 1
- 208000002249 Diabetes Complications Diseases 0.000 abstract 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 abstract 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 abstract 1
- 206010063547 Diabetic macroangiopathy Diseases 0.000 abstract 1
- 206010054044 Diabetic microangiopathy Diseases 0.000 abstract 1
- 206010012689 Diabetic retinopathy Diseases 0.000 abstract 1
- 206010056340 Diabetic ulcer Diseases 0.000 abstract 1
- 241000124008 Mammalia Species 0.000 abstract 1
- 201000009101 diabetic angiopathy Diseases 0.000 abstract 1
- 201000007025 diabetic cataract Diseases 0.000 abstract 1
- 208000033679 diabetic kidney disease Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 231100000397 ulcer Toxicity 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Esta invención se refiere a composiciones farmacéuticas que comprenden combinaciones de un agonista de GABA, un profármaco del mismo o una sal farmacéuticamente aceptable de dicho agonista de GABA o dicho profármaco y un ARI, un profármaco del mismo o una sal farmacéuticamente aceptable de dicho ARI o dicho profármaco, estuches que contienen tales combinaciones y métodos para utilizar tales combinaciones en el tratamiento de mamíferos, incluidos los seres humanos, que padecen complicaciones de la diabetes tales como neuropatía diabética, nefropatía diabética, cardiomiopatía, retinopatía diabética, microangiopatía diabética, macroangiopatía diabética, cataratas o úlceras de los pies.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US25044800P | 2000-11-30 | 2000-11-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
UY27044A1 true UY27044A1 (es) | 2002-07-31 |
Family
ID=22947799
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UY27044A UY27044A1 (es) | 2000-11-30 | 2001-11-28 | Combinación de agonistas de gaba e inhibidores de aldosa-reductasa |
Country Status (34)
Country | Link |
---|---|
US (1) | US6720348B2 (es) |
EP (1) | EP1337272A2 (es) |
JP (1) | JP2004514700A (es) |
KR (1) | KR20030059287A (es) |
CN (1) | CN1477976A (es) |
AP (1) | AP2001002359A0 (es) |
AR (1) | AR031432A1 (es) |
AU (1) | AU2002215160A1 (es) |
BG (1) | BG107812A (es) |
BR (1) | BR0115776A (es) |
CA (1) | CA2430309A1 (es) |
CR (1) | CR6962A (es) |
CZ (1) | CZ20031387A3 (es) |
DO (1) | DOP2001000294A (es) |
EA (1) | EA200300433A1 (es) |
EC (1) | ECSP034629A (es) |
EE (1) | EE200300249A (es) |
HR (1) | HRP20030419A2 (es) |
HU (1) | HUP0302555A3 (es) |
IL (1) | IL155710A0 (es) |
IS (1) | IS6787A (es) |
MA (1) | MA26965A1 (es) |
MX (1) | MXPA03004871A (es) |
NO (1) | NO20032387D0 (es) |
OA (1) | OA12413A (es) |
PA (1) | PA8534201A1 (es) |
PE (1) | PE20020598A1 (es) |
PL (1) | PL365378A1 (es) |
SK (1) | SK6092003A3 (es) |
SV (1) | SV2003000752A (es) |
TN (1) | TNSN01170A1 (es) |
UY (1) | UY27044A1 (es) |
WO (1) | WO2002043763A2 (es) |
ZA (1) | ZA200303340B (es) |
Families Citing this family (25)
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 |
US6696407B1 (en) * | 1997-03-21 | 2004-02-24 | The Regents Of The University Of California | Huntington's disease treatment comprising administering aldose reductase inhibitors to increase striatal CNTF |
US20030162754A1 (en) * | 2001-12-17 | 2003-08-28 | Tufts University | Use of GABA and GABAB agonists |
AU2003243603A1 (en) * | 2002-06-13 | 2003-12-31 | Board Of Regents, The University Of Texas System | Methods and compositions involving aldose reductase inhibitors |
CA2509605C (en) * | 2002-12-13 | 2010-10-05 | Warner-Lambert Company Llc | Alpha-2-delta ligand to treat lower urinary tract symptoms |
US20080318908A1 (en) * | 2002-12-17 | 2008-12-25 | Trustees Of Tufts College | Use of gaba and gabab agonists |
KR20050084445A (ko) * | 2002-12-20 | 2005-08-26 | 다이노젠 파마세우티컬스, 인코포레이티드 | α₂δ 서브유닛 칼슘 채널 모듈레이터를 이용한 무통증방광 질환의 치료방법 |
CN1791399A (zh) * | 2003-03-21 | 2006-06-21 | 戴诺根医药品公司 | 用α2δ亚基钙通道调节剂和平滑肌调节剂一起治疗下泌尿道病症的方法 |
KR20050036195A (ko) * | 2003-10-15 | 2005-04-20 | 고재영 | 신규한 망막병증 치료제 조성물 |
US20110092566A1 (en) * | 2004-11-19 | 2011-04-21 | Srivastava Satish K | Treatment of cancer with aldose reductase inhibitors |
US20070112017A1 (en) * | 2005-10-31 | 2007-05-17 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
US7888351B2 (en) | 2006-04-11 | 2011-02-15 | Novartis Ag | Organic compounds |
JP2010513357A (ja) * | 2006-12-22 | 2010-04-30 | ノバルティス アーゲー | Dpp−iv阻害剤としての1−アミノメチル−1−フェニル−シクロヘキサン誘導体 |
CA2685202C (en) | 2007-03-23 | 2017-11-28 | The Board Of Regents Of The University Of Texas System | Methods for treating allergic asthma |
US20090270490A1 (en) * | 2008-04-24 | 2009-10-29 | The Board Of Regents Of The University Of Texas System | Methods involving aldose reductase inhibition |
EP2116618A1 (en) | 2008-05-09 | 2009-11-11 | Agency for Science, Technology And Research | Diagnosis and treatment of Kawasaki disease |
WO2010013240A1 (en) | 2008-07-31 | 2010-02-04 | Dekel Pharmaceuticals Ltd. | Compositions and methods for treating inflammatory disorders |
GB2476202B (en) * | 2008-09-06 | 2012-04-11 | Bionevia Pharmaceuticals Inc | Novel choline cocrystal of epalrestat |
US8785483B2 (en) | 2010-12-23 | 2014-07-22 | The Board Of Regents Of The University Of Texas System | Methods for treating COPD |
US8652527B1 (en) | 2013-03-13 | 2014-02-18 | Upsher-Smith Laboratories, Inc | Extended-release topiramate capsules |
US9101545B2 (en) | 2013-03-15 | 2015-08-11 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
US20180161388A1 (en) * | 2015-05-18 | 2018-06-14 | Beth Israel Deaconess Medical Center, Inc. | Substance p, mast cell degranulation inhibitors, and peripheral neuropathy |
AU2018254556B2 (en) * | 2017-04-21 | 2024-05-02 | Steven Hoffman | Compositions and methods for treating retinopathy |
GB2571696B (en) | 2017-10-09 | 2020-05-27 | Compass Pathways Ltd | Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced |
AU2020259406A1 (en) | 2019-04-17 | 2021-11-04 | Compass Pathfinder Limited | Treatment of depression and other various disorders with psilocybin |
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CH449645A (de) | 1963-07-09 | 1968-01-15 | Ciba Geigy | Verfahren zur Herstellung neuer Aminosäuren |
CH427803A (de) | 1963-12-06 | 1967-01-15 | Geigy Ag J R | Verfahren zur Herstellung eines neuen Isoxazolderivates |
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 |
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FR2319338A1 (fr) | 1975-08-01 | 1977-02-25 | Synthelabo | Nouveaux derives de a- phenyl benzylideniques des acides amines, leur preparation et les medicaments qui en contiennent |
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IE47592B1 (en) * | 1977-12-29 | 1984-05-02 | Ici Ltd | Enzyme inhibitory phthalazin-4-ylacetic acid derivatives, pharmaceutical compositions thereof,and process for their manufacture |
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JPS5745185A (en) | 1980-07-21 | 1982-03-13 | Eisai Co Ltd | Hydantoin derivative and its preparation |
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FR2492258A1 (fr) | 1980-10-17 | 1982-04-23 | Pharmindustrie | Nouveau medicament a base d'amino-2 trifluoromethoxy-6 benzothiazole |
CA1176269A (en) | 1981-03-02 | 1984-10-16 | Kazimir Sestanj | N-naphthoylglycine derivatives |
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DE3769066D1 (de) | 1986-08-28 | 1991-05-08 | Sanwa Kagaku Kenkyusho Co | Hydantoin-derivate zur behandlung von komplikationen bei diabetes. |
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US5236945A (en) * | 1990-06-11 | 1993-08-17 | Pfizer Inc. | 1H-indazole-3-acetic acids as aldose reductase inhibitors |
GB9016978D0 (en) | 1990-08-02 | 1990-09-19 | Ici Plc | Acetamide derivatives |
US6197819B1 (en) * | 1990-11-27 | 2001-03-06 | Northwestern University | Gamma amino butyric acid analogs and optical isomers |
EP0662962A1 (en) * | 1992-09-28 | 1995-07-19 | Pfizer Inc. | Substituted pyrimidines for control of diabetic complications |
FR2774908B1 (fr) * | 1998-02-17 | 2000-06-23 | Centre Nat Rech Scient | Utilisation d'inhibiteur de la liberation du glutamate dans le traitement de l'ischemie retinienne |
GB0001662D0 (en) * | 1999-02-06 | 2000-03-15 | Zeneca Ltd | Pharmaceutical compositions |
WO2000050034A1 (en) * | 1999-02-24 | 2000-08-31 | The Regents Of The University Of California | Gaba receptors mediate inhibition of t cell responses |
ES2215570T3 (es) * | 1999-04-01 | 2004-10-16 | Pfizer Products Inc. | Compuestos para tratar y prevenir complicaciones diabeticas. |
WO2000061138A1 (en) * | 1999-04-08 | 2000-10-19 | Ortho-Mcneil Pharmaceutical, Inc. | Anticonvulsant derivatives useful in treating chronic neurodegenerative disorders |
-
2001
- 2001-11-19 AU AU2002215160A patent/AU2002215160A1/en not_active Abandoned
- 2001-11-19 JP JP2002545733A patent/JP2004514700A/ja not_active Withdrawn
- 2001-11-19 AP APAP/P/2001/002359A patent/AP2001002359A0/en unknown
- 2001-11-19 SK SK609-2003A patent/SK6092003A3/sk not_active Application Discontinuation
- 2001-11-19 CA CA002430309A patent/CA2430309A1/en not_active Abandoned
- 2001-11-19 CZ CZ20031387A patent/CZ20031387A3/cs unknown
- 2001-11-19 WO PCT/IB2001/002214 patent/WO2002043763A2/en not_active Application Discontinuation
- 2001-11-19 KR KR10-2003-7007221A patent/KR20030059287A/ko not_active Application Discontinuation
- 2001-11-19 EP EP01983740A patent/EP1337272A2/en not_active Withdrawn
- 2001-11-19 PL PL01365378A patent/PL365378A1/xx not_active Application Discontinuation
- 2001-11-19 EA EA200300433A patent/EA200300433A1/ru unknown
- 2001-11-19 OA OA1200300138A patent/OA12413A/en unknown
- 2001-11-19 BR BR0115776-0A patent/BR0115776A/pt not_active IP Right Cessation
- 2001-11-19 HU HU0302555A patent/HUP0302555A3/hu unknown
- 2001-11-19 IL IL15571001A patent/IL155710A0/xx unknown
- 2001-11-19 EE EEP200300249A patent/EE200300249A/xx unknown
- 2001-11-19 MX MXPA03004871A patent/MXPA03004871A/es unknown
- 2001-11-19 CN CNA018195954A patent/CN1477976A/zh active Pending
- 2001-11-26 DO DO2001000294A patent/DOP2001000294A/es unknown
- 2001-11-27 PE PE2001001187A patent/PE20020598A1/es not_active Application Discontinuation
- 2001-11-28 AR ARP010105542A patent/AR031432A1/es not_active Application Discontinuation
- 2001-11-28 UY UY27044A patent/UY27044A1/es not_active Application Discontinuation
- 2001-11-29 TN TNTNSN01170A patent/TNSN01170A1/fr unknown
- 2001-11-29 US US09/997,039 patent/US6720348B2/en not_active Expired - Fee Related
- 2001-11-30 PA PA20018534201A patent/PA8534201A1/es unknown
- 2001-11-30 SV SV2001000752A patent/SV2003000752A/es unknown
-
2003
- 2003-04-14 IS IS6787A patent/IS6787A/is unknown
- 2003-04-24 CR CR6962A patent/CR6962A/es not_active Application Discontinuation
- 2003-04-30 ZA ZA200303340A patent/ZA200303340B/en unknown
- 2003-05-13 BG BG107812A patent/BG107812A/bg unknown
- 2003-05-20 MA MA27166A patent/MA26965A1/fr unknown
- 2003-05-22 HR HR20030419A patent/HRP20030419A2/hr not_active Application Discontinuation
- 2003-05-27 NO NO20032387A patent/NO20032387D0/no not_active Application Discontinuation
- 2003-05-28 EC EC2003004629A patent/ECSP034629A/es unknown
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Legal Events
Date | Code | Title | Description |
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109 | Application deemed to be withdrawn |
Effective date: 20141106 |