US20040242567A1 - Use of irbesartan for the preparation of medicinal products that are useful for preventing or treating pulmonary hypertension - Google Patents

Use of irbesartan for the preparation of medicinal products that are useful for preventing or treating pulmonary hypertension Download PDF

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Publication number
US20040242567A1
US20040242567A1 US10/492,804 US49280404A US2004242567A1 US 20040242567 A1 US20040242567 A1 US 20040242567A1 US 49280404 A US49280404 A US 49280404A US 2004242567 A1 US2004242567 A1 US 2004242567A1
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US
United States
Prior art keywords
irbesartan
preventing
hypertension
treating pulmonary
pulmonary hypertension
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.)
Abandoned
Application number
US10/492,804
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English (en)
Inventor
Sylvie Cosnier-Pucheu
Dino Nisato
Alain Roccon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Aventis France
Original Assignee
Sanofi Aventis France
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Sanofi Aventis France filed Critical Sanofi Aventis France
Assigned to SANOFI-SYNTHELABO reassignment SANOFI-SYNTHELABO ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: COSNIER-PUCHEU, SYLVIE, NISATO, DINO, ROCCON, ALAIN
Publication of US20040242567A1 publication Critical patent/US20040242567A1/en
Assigned to SANOFI-AVENTIS reassignment SANOFI-AVENTIS CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: SANOFI-SYNTHELABO
Priority to US12/477,562 priority Critical patent/US8088827B2/en
Abandoned legal-status Critical Current

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Classifications

    • 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
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • 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
    • A61P7/10—Antioedematous agents; Diuretics
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a novel use of irbesartan for the preparation of medicinal products that are useful for preparing medicinal products for preventing or treating pulmonary hypertension or pulmonary arterial hypertension.
  • Irbesartan is an antagonist of the angiotensin II AT 1 receptors.
  • Irbesartan alone or in combination with a diuretic agent, is indicated in the treatment of various cardiovascular complaints, especially hypertension and diabetic nephropathy.
  • Pulmonary arterial hypertension or pulmonary hypertension corresponds to an increase in pressure in the pulmonary arterial network to above 35 mmHg; the vital prognosis of this disease is dramatic.
  • the caliber of the pulmonary arterials and vessels shrinks and the resulting pressure increase has repercussions on the right ventricle; right ventricular insufficiency is gradually manifested and gets worse.
  • one subject of the present invention is the use of irbesartan for the preparation of medicinal products that are useful for preventing or treating pulmonary hypertension or pulmonary arterial hypertension.
  • irbesartan may also be used in combination with another active principle, for the preparation of medicinal products that are useful for preventing or treating pulmonary hypertension, for example a diuretic agent such as hydrochlorothiazide, an aquaretic agent, such as a vasopressin V 2 receptor antagonist, a vasodilator, an anticoagulant, a phosphodiesterase inhibitor, prostacyclin or an endothelin receptor antagonist such as bosentan.
  • a diuretic agent such as hydrochlorothiazide
  • an aquaretic agent such as a vasopressin V 2 receptor antagonist, a vasodilator, an anticoagulant, a phosphodiesterase inhibitor, prostacyclin or an endothelin receptor antagonist such as bosentan.
  • irbesartan For its use as a medicinal product, irbesartan, a pharmaceutically acceptable salt thereof or a solvate thereof, alone or in combination with another active principle, should be formulated as a pharmaceutical composition.
  • the active principle in the pharmaceutical compositions of the present invention for oral, sublingual, inhaled, subcutaneous, intramuscular, intravenous, transdermal, local or rectal administration, may be administered in unit administration form, as a mixture with standard pharmaceutical supports, to animals and human beings.
  • the appropriate unit administration forms comprise oral forms such as tablets, gel capsules, pills, powders, granules and oral solutions or-suspensions, sublingual and buccal administration forms, aerosols, topical administration forms, implants, transdermal, subcutaneous, intramuscular, intravenous, intranasal or intraocular administration forms and rectal administration forms.
  • the active principle(s) is(are) generally formulated in dosage units.
  • the dosage unit contains 50 to 500 mg and-advantageously from 75 to 300 mg of active principle per dosage unit, for daily administrations, one or more times a day.
  • a treatment by inhalation may also be chosen; in this case, the inhaled doses are smaller.
  • the dosage that is appropriate for each patient is determined by the doctor according to the mode of administration, the age, the weight and the response of said patient.
  • a mixture of pharmaceutical excipients is added to the active principles, which may or may not be micronized, this mixture possibly being composed of diluents, for instance lactose, mannitol, microcrystalline cellulose, starch or dicalcium phosphate, binders, for instance polyvinylpyrrolidone or hydroxypropylmethylcellulose, disintegrating agents such as crosslinked polyvinylpyrrolidone, crosslinked carboxymethylcellulose or sodium croscarmellose, glidants, for instance silica or talc, and lubricants, for instance magnesium stearate, stearic acid, glyceryl tribehenate or sodium stearylfumarate.
  • diluents for instance lactose, mannitol, microcrystalline cellulose, starch or dicalcium phosphate
  • binders for instance polyvinylpyrrolidone or hydroxypropylmethylcellulose
  • disintegrating agents such as crosslinked polyvinylpyrrolidone
  • wetting agents or surfactants such as sodium lauryl sulfate, polysorbate 80 or poloxamer 188 may be added to the formulation.
  • the tablets may be made via various techniques: direct compression, dry granulation, wet granulation or hot-melting.
  • the tablets may be plain or sugar-coated (for example with sucrose) or coated with various polymers or other suitable materials.
  • the tablets may have a flash, delayed or sustained release by making polymer matrices or by using specific polymers in the film coating.
  • the gel capsules may be soft or hard, and uncoated or film-coated so as to have flash, sustained or delayed activity (for example via a gastroresistant form). They may contain not only a solid formulation formulated as above for the tablets, but also liquids or semisolids.
  • a preparation in syrup or elixir form may contain the active principle(s) together with a sweetener, preferably a calorie-free sweetener, methylparaben and propylparaben as antiseptics, and also a flavor enhancer and a suitable dye.
  • a sweetener preferably a calorie-free sweetener, methylparaben and propylparaben as antiseptics, and also a flavor enhancer and a suitable dye.
  • the water-dispersible powders or granules may contain the active principle(s) as a mixture with dispersants or wetting agents, or suspension agents, for instance polyvinylpyrrolidone or polyvidone, and also with sweeteners or flavor enhancers.
  • suppositories which are prepared with binders that melt at the rectal temperature, for example cocoa butter or polyethylene glycols.
  • aqueous suspensions for example isotonic saline solutions or sterile injectable solutions containing pharmacologically compatible dispersants and/or solubilizing agents, for example propylene glycol or butylene glycol, are used.
  • pharmacologically compatible dispersants and/or solubilizing agents for example propylene glycol or butylene glycol
  • a cosolvent for example an alcohol such as ethanol or a glycol such as polyethylene glycol or propylene glycol, and a hydrophilic surfactant such as polysorbate 80 or poloxamer 188.
  • the active principle may be dissolved with a triglyceride or a glycerol ester.
  • Creams, ointments, gels, eye drops or sprays may be used for local administration.
  • Patches in multilaminar or reservoir form in which the active principle is in alcoholic solution may be used for transdermal administration.
  • An aerosol containing, for example, sorbitan trioleate or oleic acid and also trichlorofluoromethane, dichlorofluoromethane, dichlorotetrafluoroethane, freon substitutes or any other biologically compatible propellent gas is used for administration by inhalation; a system containing the active principle alone or combined-with an excipient, in powder form, may also be used.
  • the active principle(s) may also be in the form of a complex with a cyclodextrin, for example ⁇ -, ⁇ - or ⁇ -cyclodextrin, 2-hydroxypropyl- ⁇ -cyclodextrin or methyl- ⁇ -cyclodextrin.
  • a cyclodextrin for example ⁇ -, ⁇ - or ⁇ -cyclodextrin, 2-hydroxypropyl- ⁇ -cyclodextrin or methyl- ⁇ -cyclodextrin.
  • the active principle(s) may also be formulated in the form of microcapsules or microspheres, optionally with one or more supports or additives.
  • sustained-release forms that are useful in the case of chronic treatments, use may be made of implants. These may be prepared in the form of an oily suspension or in the form of a suspension of microspheres in an isotonic medium.
  • the irbesartan is administered orally, as a single dosage intake per day or by inhalation using an aerosol, one or more times a day.
  • the invention also relates to a method that consists in administering a therapeutically effective amount of irbesartan, a pharmaceutically acceptable salt thereof or a solvate thereof.
  • MCT monocrotaline
  • the treatment with irbesartan was started either 21 days or 14 days after injection of monocrotaline. Irbesartan was incorporated into the food in powder form. The control animals received food alone.
  • irbesartan was administered alone at a dose of 50 mg/kg.
  • irbesartan was administered alone at a dose of 30 mg/kg and in combination with hydrochlorothiazide (HCTZ): irbesartan: 30 mg/kg and HCTZ: 10 mg/kg.
  • HCTZ hydrochlorothiazide
  • Irbesartan administered at a dose of 50 mg/kg/day, either from the 21st day or from the 14th day post-MCT, significantly increased the survival time of the MCT-treated rats.
  • Study 2 Survival to the end Survival to the of the study (85th Groups 50th day day) Controls 16.7% (4/24) 4.2% (1/24) Irbesartan 47.8% (11/23) 0% (0/23) 30 mg/kg HCTZ 25% (6/24) 4.2% (1/24) 10 mg/kg Irbesartan 30 mg/kg 60.9% (14/23) 39.1% (9/23) HCTZ 10 mg/kg
  • EXAMPLE 1 EXAMPLE 2
  • EXAMPLE 3 Irbesartan 75.00 mg 150.00 mg 300.00 mg Lactose monohydrate 15.38 mg 30.75 mg 61.50 mg Microcrystalline 19.50 mg 39.00 mg 78.00 mg cellulose Pregelatinized 22.50 mg 45.00 mg 90.00 mg corn starch Sodium croscarmellose 7.50 mg 15.00 mg 30.00 mg Poloxamer 188 4.50 mg 9.00 mg 18.00 mg Hydrated colloidal 4.12 mg 8.25 mg 16.50 mg silica Magnesium stearate 1.50 mg 3.00 mg 6.00 mg Purified water qs qs qs 150.00 mg 300.00 mg 600.00 mg
  • EXAMPLE 4 EXAMPLE 5 Irbesartan 150.00 mg 300.00 mg Hydrochlorothiazide 12.50 mg 12.50 mg Lactose monohydrate 26.65 mg 65.80 mg Microcrystalline cellulose 45.00 mg 90.00 mg Pregelatinized corn starch 45.00 mg 90.00 mg Sodium croscarmellose 15.00 mg 30.00 mg Red iron oxide 0.30 mg 0.60 mg Yellow iron oxide 0.30 mg 0.60 mg Hydrated colloidal silica 2.25 mg 4.50 mg Magnesium stearate 3.00 mg 6.00 mg Purified water qs qs 300.00 mg 600.00 mg 600.00 mg

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
US10/492,804 2001-10-26 2002-10-09 Use of irbesartan for the preparation of medicinal products that are useful for preventing or treating pulmonary hypertension Abandoned US20040242567A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/477,562 US8088827B2 (en) 2001-10-26 2009-06-03 Use of irbesartan for the preparation of medicinal products that are useful for treating pulmonary hypertension

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR01/13936 2001-10-26
FR0113936A FR2831446B1 (fr) 2001-10-26 2001-10-26 Utilisation de l'irbesartan pour la preparation de medicaments utiles pour la prevention ou le traitement de l'hypertension pulmonaire
PCT/FR2002/003439 WO2003035062A1 (fr) 2001-10-26 2002-10-09 Utilisation de l'irbesartan pour la preparation de medicaments utiles pour la prevention ou le traitement de l'hypertension pulmonaire

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/477,562 Continuation US8088827B2 (en) 2001-10-26 2009-06-03 Use of irbesartan for the preparation of medicinal products that are useful for treating pulmonary hypertension

Publications (1)

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US20040242567A1 true US20040242567A1 (en) 2004-12-02

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US10/492,804 Abandoned US20040242567A1 (en) 2001-10-26 2002-10-09 Use of irbesartan for the preparation of medicinal products that are useful for preventing or treating pulmonary hypertension
US12/477,562 Expired - Fee Related US8088827B2 (en) 2001-10-26 2009-06-03 Use of irbesartan for the preparation of medicinal products that are useful for treating pulmonary hypertension

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Application Number Title Priority Date Filing Date
US12/477,562 Expired - Fee Related US8088827B2 (en) 2001-10-26 2009-06-03 Use of irbesartan for the preparation of medicinal products that are useful for treating pulmonary hypertension

Country Status (24)

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US (2) US20040242567A1 (enrdf_load_stackoverflow)
EP (1) EP1441723B1 (enrdf_load_stackoverflow)
JP (1) JP4542777B2 (enrdf_load_stackoverflow)
CN (1) CN100418526C (enrdf_load_stackoverflow)
AT (1) ATE361071T1 (enrdf_load_stackoverflow)
AU (1) AU2002350832B2 (enrdf_load_stackoverflow)
BR (1) BR0213479A (enrdf_load_stackoverflow)
CA (1) CA2461625C (enrdf_load_stackoverflow)
CY (1) CY1106746T1 (enrdf_load_stackoverflow)
DE (1) DE60219940T2 (enrdf_load_stackoverflow)
DK (1) DK1441723T3 (enrdf_load_stackoverflow)
EA (1) EA007952B1 (enrdf_load_stackoverflow)
ES (1) ES2286304T3 (enrdf_load_stackoverflow)
FR (1) FR2831446B1 (enrdf_load_stackoverflow)
HU (1) HUP0401633A3 (enrdf_load_stackoverflow)
IL (2) IL161116A0 (enrdf_load_stackoverflow)
IS (1) IS2849B (enrdf_load_stackoverflow)
MX (1) MXPA04003910A (enrdf_load_stackoverflow)
NO (1) NO332313B1 (enrdf_load_stackoverflow)
NZ (1) NZ532130A (enrdf_load_stackoverflow)
PL (1) PL209263B1 (enrdf_load_stackoverflow)
PT (1) PT1441723E (enrdf_load_stackoverflow)
WO (1) WO2003035062A1 (enrdf_load_stackoverflow)
ZA (1) ZA200402696B (enrdf_load_stackoverflow)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060104913A1 (en) * 2003-06-27 2006-05-18 Merck Patent Gmbh Inhalable formulations for treating pulmonary hypertension and methods of using same
WO2006067601A1 (en) * 2004-12-23 2006-06-29 Ranbaxy Laboratories Limited Oral pharmaceutical compositions of irbesartan and hydrochlorothiazide and processes for their preparation
WO2008026012A1 (en) * 2006-08-31 2008-03-06 Generics [Uk] Limited Novel compositions and methods
WO2022198264A1 (en) * 2021-03-23 2022-09-29 Dimerix Bioscience Pty Ltd Treatment of inflammatory diseases

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9808471B2 (en) 2003-04-16 2017-11-07 Mylan Specialty Lp Nasal pharmaceutical formulations and methods of using the same
US8912174B2 (en) 2003-04-16 2014-12-16 Mylan Pharmaceuticals Inc. Formulations and methods for treating rhinosinusitis
US7811606B2 (en) 2003-04-16 2010-10-12 Dey, L.P. Nasal pharmaceutical formulations and methods of using the same
TR200301553A1 (tr) * 2003-09-18 2005-10-21 Nobel �La� Sanay�� Ve T�Caret A.�. İrbesartan etken maddesi içeren yeni oral farmasötik formülasyonlar
ES2282062T1 (es) 2004-06-04 2007-10-16 Teva Pharmaceutical Industries Ltd. Composicion farmaceutica que contiene irbesartan.
CN100367959C (zh) * 2006-08-29 2008-02-13 陈俊云 一种含有依贝沙坦的药物

Citations (4)

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US5258510A (en) * 1989-10-20 1993-11-02 Otsuka Pharma Co Ltd Benzoheterocyclic compounds
US5270317A (en) * 1990-03-20 1993-12-14 Elf Sanofi N-substituted heterocyclic derivatives, their preparation and the pharmaceutical compositions in which they are present
US5292740A (en) * 1991-06-13 1994-03-08 Hoffmann-La Roche Inc. Sulfonamides
US5292741A (en) * 1992-08-18 1994-03-08 Merck & Co., Inc. Macrocycles incorporating quinazolinones

Family Cites Families (2)

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Publication number Priority date Publication date Assignee Title
NZ237476A (en) * 1990-03-20 1994-01-26 Sanofi Sa N-substituted heterocyclic compounds and pharmaceutical compositions.
US20020068740A1 (en) 1999-12-07 2002-06-06 Mylari Banavara L. Combination of aldose reductase inhibitors and antihypertensive agents for the treatment of diabetic complications

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5258510A (en) * 1989-10-20 1993-11-02 Otsuka Pharma Co Ltd Benzoheterocyclic compounds
US5270317A (en) * 1990-03-20 1993-12-14 Elf Sanofi N-substituted heterocyclic derivatives, their preparation and the pharmaceutical compositions in which they are present
US5292740A (en) * 1991-06-13 1994-03-08 Hoffmann-La Roche Inc. Sulfonamides
US5292741A (en) * 1992-08-18 1994-03-08 Merck & Co., Inc. Macrocycles incorporating quinazolinones

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060104913A1 (en) * 2003-06-27 2006-05-18 Merck Patent Gmbh Inhalable formulations for treating pulmonary hypertension and methods of using same
US9498437B2 (en) 2003-06-27 2016-11-22 Mylan Specialty L.P. Inhalable formulations for treating pulmonary hypertension and methods of using same
WO2006067601A1 (en) * 2004-12-23 2006-06-29 Ranbaxy Laboratories Limited Oral pharmaceutical compositions of irbesartan and hydrochlorothiazide and processes for their preparation
WO2008026012A1 (en) * 2006-08-31 2008-03-06 Generics [Uk] Limited Novel compositions and methods
US20090312380A1 (en) * 2006-08-31 2009-12-17 Axel Becker Novel compositions and methods
WO2022198264A1 (en) * 2021-03-23 2022-09-29 Dimerix Bioscience Pty Ltd Treatment of inflammatory diseases

Also Published As

Publication number Publication date
IS2849B (is) 2013-09-15
ES2286304T3 (es) 2007-12-01
DE60219940D1 (de) 2007-06-14
EA007952B1 (ru) 2007-02-27
JP4542777B2 (ja) 2010-09-15
DE60219940T2 (de) 2008-01-17
MXPA04003910A (es) 2004-07-23
CN100418526C (zh) 2008-09-17
CA2461625C (en) 2011-07-05
NZ532130A (en) 2006-10-27
CY1106746T1 (el) 2012-05-23
US20090247510A1 (en) 2009-10-01
EP1441723B1 (fr) 2007-05-02
IL161116A (en) 2010-12-30
HUP0401633A3 (en) 2009-06-29
NO20041732L (no) 2004-07-23
ZA200402696B (en) 2005-06-29
WO2003035062A1 (fr) 2003-05-01
PL368737A1 (en) 2005-04-04
DK1441723T3 (da) 2007-09-10
EA200400438A1 (ru) 2004-10-28
IL161116A0 (en) 2004-08-31
PT1441723E (pt) 2007-07-26
NO332313B1 (no) 2012-08-27
US8088827B2 (en) 2012-01-03
JP2005506369A (ja) 2005-03-03
BR0213479A (pt) 2004-11-03
FR2831446B1 (fr) 2004-03-05
CN1610548A (zh) 2005-04-27
PL209263B1 (pl) 2011-08-31
EP1441723A1 (fr) 2004-08-04
CA2461625A1 (en) 2003-05-01
ATE361071T1 (de) 2007-05-15
AU2002350832B2 (en) 2006-11-30
IS7200A (is) 2004-03-29
FR2831446A1 (fr) 2003-05-02
HUP0401633A2 (hu) 2004-12-28

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