EP1178809A1 - Pharmaceutical composition in unit form containing acetylsalcylic acid and clopidogrel hydrogenosulphate - Google Patents
Pharmaceutical composition in unit form containing acetylsalcylic acid and clopidogrel hydrogenosulphateInfo
- Publication number
- EP1178809A1 EP1178809A1 EP00922737A EP00922737A EP1178809A1 EP 1178809 A1 EP1178809 A1 EP 1178809A1 EP 00922737 A EP00922737 A EP 00922737A EP 00922737 A EP00922737 A EP 00922737A EP 1178809 A1 EP1178809 A1 EP 1178809A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- pharmaceutical composition
- acetylsalicylic acid
- clopidogrel
- hydrogen sulfate
- composition according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic 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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- 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
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- 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
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- A61P9/10—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
-
- 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
Definitions
- composition in unit form containing acetylsalicylic acid and clopidogrel hydrogen sulfate
- the present invention relates to a pharmaceutical composition in a unit dosage form containing an association of active principles with antiplatelet activity consisting of acetylsalicylic acid, also known under the brand name Aspirin, and clopidogrel hydrogen sulfate.
- the unit dosage form can be administered orally and preferably consists of a tablet, a capsule or a dose sachet.
- acetylsalicylic acid is used in its acid form and clopidogrel hydrogen sulphate can be used in the form of one or other of its polymorphs known to date and called Form 1 (F1) or Form 2 (F2).
- Form 1 is the salt described in patent EP 281459 and clopidogrel hydrogen sulfate Form 2 is that described in patent application FR 98 07464.
- the therapeutic advantage of the combination of acetylsalicylic acid and of clopidogrel is among others described in patent application WO 97/29753.
- compositions are mentioned there without ever specifying that the pharmaceutically acceptable salt used is clopidogrel hydrogen sulfate. This document always indicates that the composition can be used parenterally or orally and that it is possible to administer the active ingredients according to four modes of administration, namely, both orally, both parenterally or one orally and the other parenterally or vice versa.
- the tablets according to the invention can be obtained by various manufacturing processes such as for example:
- the direct compression process in which the active ingredients and the selected excipients are mixed.
- the mixture obtained is sieved (calibrated) on a previously defined mesh opening grid, in order to homogenize the particle sizes of the constituents.
- a new mixing is carried out to ensure good homogeneity of the active ingredients.
- Specific excipients (example: a flow agent) as well as a lubricant are added and mixed.
- the final mixture obtained is then compressed.
- Dry granulation consists in ensuring that the active ingredients and the selected excipients are mixed, calibrated and then mixed again.
- the mixture is forced between two mobile cylinders, in opposite directions of rotation, in order to obtain, according to the forces exerted, plates of determined mechanical strengths. These plates are calibrated.
- the specific excipients are added and the final mixture compressed.
- Hot melt granulation is a granulation process that can be used when an active ingredient degrades in the presence of water.
- the active ingredients and the selected excipients are calibrated and then mixed.
- the mixture is brought under slow stirring to a temperature slightly higher than that of the melting point of the excipient, mixed under rapid stirring, then cooled to room temperature.
- the grain obtained is calibrated.
- the specific excipients are added and the final mixture compressed.
- An example of a "hot melt” process in a granulator with a fluidized air bed is described below.
- the active ingredients and the selected excipients, except the fusible excipient are calibrated and then transferred to a granulator with a fluidized air bed.
- the whole is mixed by fluidization with supply of hot air, up to a temperature of the mixture slightly lower than that of the melting point of the granulation excipient.
- the molten excipient is then sprayed onto the fluidized mixture.
- the temperature of the fluidizing air is lowered.
- the grain obtained is calibrated.
- the specific excipients are added and the final mixture compressed.
- the capsules and dose sachets are prepared according to techniques well known to those skilled in the art.
- the pharmaceutical compositions according to the invention are used for the treatment of a pathology induced by platelet aggregation including stable or unstable angina, disorders of the cardiovascular and cerebrovascular system such as thromboembolic disorders associated with atherosclerosis and diabetes such as unstable angina, cerebral attack, restenosis after angioplasty, endarterectomy or fitting of metal endovascular prostheses or thromboembolic disorders associated with rethrombosis after thrombolysis, infarction, dementia of ischemic origin, peripheral arterial diseases, hemodialysis, atrial fibrillation or even when using vascular prostheses, bypass surgery, or during radiotherapy to reduce side effects.
- compositions according to the invention are used for the preparation of a medicament intended for the treatment of the pathologies mentioned above and allow the treatment of these pathologies.
- clopidogrel hydrogen sulfate and acetylsalicylic acid are present in a molar ratio of clopidogrel hydrogenosulfate / acetylsalicylic acid comprised between 2.5 and 11, preferably between 5 and 9.
- clopidogrel hydrogen sulfate 1 to 500 mg per day of clopidogrel hydrogen sulfate and 1 to 500 mg per day of acetylsalicylic acid are administered to humans, the doses being expressed in equivalent amounts of clopidogrel in free form.
- clopidogrel hydrogen sulfate is administered and 75 to
- compositions containing 97.875 mg of clopidogrel hydrogen sulfate and 75 mg of acetylsalicylic acid are particularly preferred.
- compositions containing 97.875 mg of clopidogrel hydrogen sulfate and 375 mg of acetylsalicylic acid Preference is also given to compositions containing 97.875 mg of clopidogrel hydrogen sulfate and 375 mg of acetylsalicylic acid.
- Example granulation process by compacting
- Anhydrous lactose ⁇ can be replaced in an equivalent amount with mannitol.
- Example granulation process by compacting
- Mannitol can be replaced in an equivalent amount by anhydrous lactose ⁇ .
- a) 97.875 g of clopidogrel hydrogenosulfate are mixed with 2 g of anhydrous colloidal silica b) 325 g of acetylsalicylic acid, 30 g of corn starch, 124.6 g of mannitol and 60 g of microcrystalline cellulose are added to a) and mixed c)
- the mixture b) is calibrated and then mixed again d) 10.5 g of hydrogenated castor oil are added to c) before the final mixture e)
- the final mixture is compressed to a theoretical unit mass of 650 mg
- the mixture is made in mini-rhôn for 10 minutes between the active ingredients and the diluents.
- the active ingredients are mixed with the mini-rhôn for 10 minutes with the diluents.
- Anhydrous colloidal silica is added to the above mixture and then sieved through a grid of 0.315 mm mesh opening.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Surgery (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9905497 | 1999-04-30 | ||
FR9905497A FR2792836B3 (en) | 1999-04-30 | 1999-04-30 | PHARMACEUTICAL COMPOSITION IN UNIT FORM CONTAINING ASPIRIN AND CLOPIDOGREL HYDROGENOSULFATE |
PCT/FR2000/001086 WO2000066130A1 (en) | 1999-04-30 | 2000-04-25 | Pharmaceutical composition in unit form containing acetylsalcylic acid and clopidogrel hydrogenosulphate |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1178809A1 true EP1178809A1 (en) | 2002-02-13 |
Family
ID=9545071
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP00922737A Withdrawn EP1178809A1 (en) | 1999-04-30 | 2000-04-25 | Pharmaceutical composition in unit form containing acetylsalcylic acid and clopidogrel hydrogenosulphate |
Country Status (24)
Country | Link |
---|---|
EP (1) | EP1178809A1 (en) |
JP (1) | JP2002543137A (en) |
KR (1) | KR20020005735A (en) |
CN (1) | CN1359294A (en) |
AR (1) | AR023789A1 (en) |
AU (1) | AU4303600A (en) |
BR (1) | BR0010194A (en) |
CA (1) | CA2371231A1 (en) |
CZ (1) | CZ20013887A3 (en) |
EA (1) | EA200100959A1 (en) |
EE (1) | EE200100559A (en) |
FR (1) | FR2792836B3 (en) |
HK (1) | HK1041823A1 (en) |
HU (1) | HUP0202329A2 (en) |
IL (1) | IL145648A0 (en) |
IS (1) | IS6084A (en) |
MX (1) | MXPA01011071A (en) |
NO (1) | NO20015295L (en) |
NZ (1) | NZ514248A (en) |
PL (1) | PL351923A1 (en) |
SK (1) | SK15542001A3 (en) |
TR (1) | TR200103039T2 (en) |
UY (1) | UY26131A1 (en) |
WO (1) | WO2000066130A1 (en) |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60135780D1 (en) | 2000-12-25 | 2008-10-23 | Daiichi Sankyo Co Ltd | ASPIRIN-CONTAINING MEDICAL COMPOSITIONS |
US6767913B2 (en) | 2001-12-18 | 2004-07-27 | Teva Pharmaceutical Industries Ltd. | Crystal forms iii, iv, v, and novel amorphous form of clopidogrel hydrogensulfate, processes for their preparation, processes for the preparation of form i, compositions containing the new forms and methods of administering the new forms |
US7074928B2 (en) | 2002-01-11 | 2006-07-11 | Teva Pharmaceutical Industries, Ltd. | Polymorphs of clopidogrel hydrogensulfate |
US6800759B2 (en) | 2002-08-02 | 2004-10-05 | Teva Pharmaceutical Industries Ltd. | Racemization and enantiomer separation of clopidogrel |
IL166593A0 (en) | 2002-08-02 | 2006-01-15 | Racemization and enantiomer separation of clopidogrel | |
JP4917255B2 (en) * | 2003-10-16 | 2012-04-18 | 第一三共ヘルスケア株式会社 | Oral composition containing salicylic acids |
WO2005070464A2 (en) * | 2004-01-21 | 2005-08-04 | Biofarma Ilac Sanayi Ve Ticaret A.S. | A tablet formulation of clopidogrel bisulphate |
JP2008543843A (en) * | 2005-06-13 | 2008-12-04 | エラン ファーマ インターナショナル リミテッド | Combination preparation of nanoparticulate clopidogrel and aspirin |
KR20070009851A (en) * | 2005-07-14 | 2007-01-19 | 씨제이 주식회사 | Pharmaceutical compositions containing clopidogrel bisulfate |
KR100736024B1 (en) * | 2005-09-21 | 2007-07-06 | 주식회사종근당 | Novel resinate complex of S-clopidogrel and production method thereof |
KR20070044323A (en) * | 2005-10-24 | 2007-04-27 | 에스케이케미칼주식회사 | Stabilized pharmaceutical oral preparation containing clopidogrel bisulfate |
US20100145053A1 (en) * | 2006-04-05 | 2010-06-10 | Cadila Healthcare Limited | Modified release clopidogrel formulation |
EP1900358A1 (en) * | 2006-09-16 | 2008-03-19 | Cimex Pharma AG | Pharmaceutical formulations comprising clopidogrel |
HUP0600839A3 (en) * | 2006-11-14 | 2008-09-29 | Egis Gyogyszergyar Nyrt | Solid pharmaceutical composition containing polymorph i of clopidogrel hydrogensulfate and process for the preparation thereof |
EP2255797A4 (en) * | 2008-02-22 | 2011-09-07 | Hanall Biopharma Co Ltd | Composite preparation |
CN101695496A (en) * | 2009-10-15 | 2010-04-21 | 苏春华 | Medicinal composition containing triflusal and clopidogrel |
JP2013032289A (en) * | 2009-10-28 | 2013-02-14 | Daiichi Sankyo Co Ltd | Wax stable formulation |
RU2484820C2 (en) * | 2011-02-24 | 2013-06-20 | Общество с ограниченной ответственностью "Озон" | Combined medicine as thrombocyte aggregation inhibitor |
KR101675501B1 (en) | 2011-11-02 | 2016-11-14 | 한국유나이티드제약 주식회사 | Combination of Clopidogrel and Aspirin |
CN102406938A (en) * | 2011-11-29 | 2012-04-11 | 北京阜康仁生物制药科技有限公司 | Medicine composition for resisting thrombosis |
JP6004524B2 (en) * | 2012-07-11 | 2016-10-12 | 大原薬品工業株式会社 | Method for producing clopidogrel sulfate-containing tablets |
JP5905165B2 (en) * | 2013-08-02 | 2016-04-20 | サノフイ | Pharmaceutical tablets containing acetylsalicylic acid and clopidogrel |
CN104434932B (en) * | 2014-12-18 | 2017-05-24 | 成都苑东生物制药股份有限公司 | Pharmaceutical composition of clopidogrel hydrogen sulfate and acetylsalicylic acid tablet and preparation method thereof |
WO2017037741A1 (en) * | 2015-09-02 | 2017-03-09 | Sun Pharmaceutical Industries Ltd | Compact solid dosage form of aspirin and clopidogrel |
CN115737578A (en) * | 2022-11-23 | 2023-03-07 | 石家庄四药有限公司 | Clopidogrel hydrogen sulfate and aspirin compound tablet and preparation method thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2623810B2 (en) | 1987-02-17 | 1992-01-24 | Sanofi Sa | ALPHA SALTS- (TETRAHYDRO-4,5,6,7 THIENO (3,2-C) PYRIDYL-5) (2-CHLORO-PHENYL) -THETHYL ACETATE DEXTROGYRE AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME |
US5576328A (en) * | 1994-01-31 | 1996-11-19 | Elf Sanofi | Method for the secondary prevention of ischemic events |
FR2744918B1 (en) | 1996-02-19 | 1998-05-07 | Sanofi Sa | NEW COMBINATIONS OF ACTIVE INGREDIENTS CONTAINING THIENO (3,2-C) PYRIDINE DERIVATIVE AND AN ANTITHROMBOTIC |
FR2779726B1 (en) | 1998-06-15 | 2001-05-18 | Sanofi Sa | POLYMORPHIC FORM OF CLOPIDOGREL HYDROGENOSULFATE |
-
1999
- 1999-04-30 FR FR9905497A patent/FR2792836B3/en not_active Expired - Fee Related
-
2000
- 2000-04-25 MX MXPA01011071A patent/MXPA01011071A/en unknown
- 2000-04-25 EE EEP200100559A patent/EE200100559A/en unknown
- 2000-04-25 CA CA002371231A patent/CA2371231A1/en not_active Abandoned
- 2000-04-25 NZ NZ514248A patent/NZ514248A/en unknown
- 2000-04-25 IL IL14564800A patent/IL145648A0/en unknown
- 2000-04-25 SK SK1554-2001A patent/SK15542001A3/en unknown
- 2000-04-25 EP EP00922737A patent/EP1178809A1/en not_active Withdrawn
- 2000-04-25 CZ CZ20013887A patent/CZ20013887A3/en unknown
- 2000-04-25 HU HU0202329A patent/HUP0202329A2/en unknown
- 2000-04-25 BR BR0010194-0A patent/BR0010194A/en not_active Application Discontinuation
- 2000-04-25 JP JP2000615014A patent/JP2002543137A/en not_active Withdrawn
- 2000-04-25 CN CN00807001A patent/CN1359294A/en active Pending
- 2000-04-25 AU AU43036/00A patent/AU4303600A/en not_active Abandoned
- 2000-04-25 TR TR2001/03039T patent/TR200103039T2/en unknown
- 2000-04-25 KR KR1020017013830A patent/KR20020005735A/en not_active Application Discontinuation
- 2000-04-25 WO PCT/FR2000/001086 patent/WO2000066130A1/en not_active Application Discontinuation
- 2000-04-25 EA EA200100959A patent/EA200100959A1/en unknown
- 2000-04-25 PL PL00351923A patent/PL351923A1/en not_active Application Discontinuation
- 2000-04-28 AR ARP000102020A patent/AR023789A1/en unknown
- 2000-04-28 UY UY26131A patent/UY26131A1/en not_active Application Discontinuation
-
2001
- 2001-09-25 IS IS6084A patent/IS6084A/en unknown
- 2001-10-29 NO NO20015295A patent/NO20015295L/en not_active Application Discontinuation
-
2002
- 2002-05-14 HK HK02103639.9A patent/HK1041823A1/en unknown
Non-Patent Citations (1)
Title |
---|
See references of WO0066130A1 * |
Also Published As
Publication number | Publication date |
---|---|
TR200103039T2 (en) | 2002-01-21 |
CA2371231A1 (en) | 2000-11-09 |
HK1041823A1 (en) | 2002-07-26 |
EA200100959A1 (en) | 2002-06-27 |
SK15542001A3 (en) | 2002-02-05 |
NO20015295L (en) | 2001-12-21 |
MXPA01011071A (en) | 2002-07-22 |
AR023789A1 (en) | 2002-09-04 |
NZ514248A (en) | 2003-06-30 |
UY26131A1 (en) | 2000-12-29 |
EE200100559A (en) | 2003-02-17 |
AU4303600A (en) | 2000-11-17 |
IS6084A (en) | 2001-09-25 |
FR2792836B3 (en) | 2001-07-27 |
BR0010194A (en) | 2002-02-13 |
NO20015295D0 (en) | 2001-10-29 |
HUP0202329A2 (en) | 2002-10-28 |
PL351923A1 (en) | 2003-06-30 |
CN1359294A (en) | 2002-07-17 |
WO2000066130A1 (en) | 2000-11-09 |
CZ20013887A3 (en) | 2002-02-13 |
FR2792836A1 (en) | 2000-11-03 |
IL145648A0 (en) | 2002-06-30 |
JP2002543137A (en) | 2002-12-17 |
KR20020005735A (en) | 2002-01-17 |
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