EP1729767A1 - Kombination aus einer heterozyklischen verbindung und einem antioxidans und ihre verwendung zur behandlung von adipositas - Google Patents

Kombination aus einer heterozyklischen verbindung und einem antioxidans und ihre verwendung zur behandlung von adipositas

Info

Publication number
EP1729767A1
EP1729767A1 EP05744511A EP05744511A EP1729767A1 EP 1729767 A1 EP1729767 A1 EP 1729767A1 EP 05744511 A EP05744511 A EP 05744511A EP 05744511 A EP05744511 A EP 05744511A EP 1729767 A1 EP1729767 A1 EP 1729767A1
Authority
EP
European Patent Office
Prior art keywords
branched
linear
group
phenyl
ethoxy
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Withdrawn
Application number
EP05744511A
Other languages
English (en)
French (fr)
Inventor
Louis Casteilla
Luc Penicaud
Pascal Berthelot
Catherine Dacquet
Daniel-Henri Caignard
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.)
Centre National de la Recherche Scientifique CNRS
Laboratoires Servier SAS
Original Assignee
Centre National de la Recherche Scientifique CNRS
Laboratoires Servier SAS
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 Centre National de la Recherche Scientifique CNRS, Laboratoires Servier SAS filed Critical Centre National de la Recherche Scientifique CNRS
Publication of EP1729767A1 publication Critical patent/EP1729767A1/de
Withdrawn legal-status Critical Current

Links

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
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • 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
    • A61K31/13—Amines
    • A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin

Definitions

  • the present invention relates to a new association between a heterocyclic derivative and an antioxidant agent for obtaining pharmaceutical compositions useful in the treatment and / or prevention of obesity and overweight characterized by a body weight index greater than 25.
  • Obesity is a major public health problem in all developed countries. Also growing steadily in developing countries, it is reaching an increasingly young population. Obesity is a well-established risk factor for cardiovascular disease and is associated with a significant increase in the risk of stroke, non-insulin-dependent diabetes, gallbladder stones, respiratory dysfunction, osteoarthritis, many forms of cancer and premature death. In obese people, it has been shown that the generation of reactive oxygen species released by monocytes and leukocytes was greatly increased compared to non-obese subjects (J. Clin. Endocrinol. Metab., 2001, 86, 355-362 ). The high plasma concentrations of tumor necrosis factor alpha (TNF ⁇ ) in the obese stimulate inflammatory processes (J. Clin.
  • a strategy aimed at reducing the body's "oxidation load" while promoting lipid and carbohydrate metabolism should lead to an exacerbation of the effects and consequently to weight loss in obese or overweight subjects.
  • the present invention relates more particularly to the association between a derivative promoting lipid and carbohydrate metabolism of the organism and an antioxidant agent.
  • the invention relates to the association between a derivative promoting lipid and carbohydrate metabolism having a heterocyclic structure and an antioxidant agent.
  • heterocyclic derivatives promoting the lipid and carbohydrate metabolisms according to the invention are more particularly the compounds of formula (I):
  • R ′ 2 IX represents an oxygen or sulfur atom, or a CH 2 or CH group (in which R ′ forms with R an additional bond)
  • 1 7 R and R which are identical or different, represent a hydrogen atom, a linear or branched (Cj-C 6 ) alkyl, aryl, linear or branched arylalkyl (C ⁇ -C 6 ), aryloxy, arylalkyloxy (C ⁇ -C 6 ) linear or branched, linear or branched alkoxy (C ⁇ -C 6 ) group, hydroxy, amino, alkylamino (C ⁇ -C 6 ) linear or branched or dialkylamino (C ⁇ -C 6 ) linear or branched, or R and R together form an oxo, thioxo or imino group
  • R 2 can also form with R ' 2 an additional link
  • A represents an alkylene chain (C ⁇ -C 6 ) of which a CH 2 group can be replaced by a heteroatom chosen from oxygen or sulfur, or by a group NR a (where R a represents a hydrogen atom or an alkyl group ( C ⁇ -C 6 ) linear or branched), or by a phenylene or naphthylene group,
  • R 3 and R 4 identical or different, represent a hydrogen or halogen atom, or a group R, OR or NRR '(where R and R', identical or different, represent a hydrogen atom or a alkyl (C.-C 6) linear or branched, alkenyl (C -C 6) linear or branched alkynyl (C 2 -C 6) linear or branched, aryl, aryl (C ⁇ -C6) linear or branched arylalkenyl (C -C 6 ) linear or branched, arylalkynyl (C -C 6 ) linear or branched, heteroaryl, heteroarylalkyl (C ⁇ -C 6 ) linear or branched, heteroarylalkenyl (C 2 -C 6 ) linear or branched, heteroarylalkynyl (C 2 -C 6 ) linear or branched, cycloalkyl (C 3 -C 8 ), cycloalkyl
  • R 5 and R 6 can take all the values of R as defined above, D represents: R ′ 2 I a benzene nucleus and in this case X cannot represent a CH group as defined above, or D represents a pyridine, pyrazine, pyrimidine or pyridine ring,
  • B represents a linear or branched (C ⁇ -C 6 ) alkyl group, or a linear or branched (C -C 6 ) alkenyl group, these groups being substituted: by a group of formula (II):
  • ZM z M z - R ' represents a group C ⁇ -OR II -C— NRR', - N (R) C— R 'ZM or - N (R) C— OR' in which Z represents an atom of oxygen or sulfur and R and R ′, identical or different, can take the same values as defined above,
  • R represents an aryl, arylalkyl group in which the alkyl part contains from 1 to 6 carbon atoms and can be linear or branched, heteroaryl, heteroarylalkyl in which the alkyl part contains 1 to 6 carbon atoms and can be linear or branched, CN , tetrazole, 0 R, NRR ', - N (R) C— R' or - N (R) C OR ', ZZ in which Z is as defined above and R and R', identical or different, can take the same values as defined above, * or by a group R 9 where R 9 represents a group CN, tetrazole,
  • R and R ′ in which Z is as defined previously and R and R ′, identical or different, can take the same values as defined previously, n represents 0, 1, 2, 3, 4, 5 or 6, and R 10 and R 11 , identical or different, represent a hydrogen atom or a linear or branched (C ⁇ -C 6 ) alkyl group, it being understood that R 10 and R 11 cannot simultaneously represent a hydrogen atom,
  • aryl is understood to mean a phenyl, naphthyl or biphenyl group, these groups possibly being partially hydrogenated,
  • heteroaryl means any mono or bicyclic aromatic group containing 5 to 10 links, which can be partially hydrogenated on one of the rings in the case of bicyclic heteroaryls, and containing 1 to 3 heteroatoms chosen from oxygen, nitrogen and sulfur,
  • the aryl and heteroaryl groups so defined may be substituted by 1 to 3 groups selected from alkyl (C ⁇ -C6) linear or branched polyhaloalkyl (C ⁇ -C6) straight or branched alkoxy (C ⁇ -C6) linear or branched, hydroxy, carboxy, formyl, N b R c
  • Rb and Rc identical or different, represent a hydrogen atom, a linear or branched alkyl group (C ⁇ -C 6 , aryl or heteroaryl), ester, amido, nitro, cyano, or halogen atoms, their enantiomers and diastereoisomers as well as their addition salts with a pharmaceutically acceptable acid or base.
  • heterocyclic derivatives of the combination according to the invention are the compounds of formula (I) for which:
  • X represents a sulfur atom
  • A represents a CH 2 - CH 2 O chain
  • R 3 and R 4 simultaneously represent a hydrogen atom
  • R 5 represents a hydrogen atom or an alkyl group
  • R 6 represents a phenyl or phenyl group substituted and more particularly substituted by a halogen atom
  • R x , R y and R z identical or different, represent:
  • a hydrogen atom or an alkyl group such as for example the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertbutyl, pentyl, isopentyl, neopentyl, hexyl groups, a polyhalogeno alkyl group such as for example the trifluoromethyl or trifluoroethyl groups, or a phenyl or benzyl group.
  • the heterocyclic derivatives of the combination according to the invention are:
  • the antioxidant agents according to the invention are more particularly anti-free radicals or scavengers for free radicals, anti-lipoperoxidizing agents, chelating agents or agents capable of regenerating endogenous antioxidants such as glutathione, vitamin C or vitamin E, as well as their addition salts with a pharmaceutically acceptable acid or base.
  • hydrochloric hydrobromic, sulfuric, phosphonic, acetic, trifluoroacetic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, tartaric, maleic, citric, ascorbic, oxalic, methane acids. sulfonic, camphoric, etc.
  • the antioxidant agent of the combination according to the invention is more preferably represented by quinone derivatives such as ubiquinone or coenzyme Qio, which acts as a free radical scavenger but which is also capable of regenerating vitamin E.
  • the preferred combination according to the invention is 2-ethoxy-3- ⁇ 4- [2- (6 - [(hydroxyimino) (phenyl) methyl) -2-oxo-1,3-benzothiazol-3 (2H) ) -yl) ethoxy] phenyl ⁇ propanoic and coenzyme Q ⁇ 0 .
  • association according to the invention between a compound promoting lipid and carbohydrate metabolism and an antioxidant agent has quite surprising pharmacological properties: the Applicant has indeed demonstrated the existence of a synergy between the two compounds of the association allowing to obtain a very significant reduction in body fat making it useful in the treatment and / or prevention of obesity and overweight characterized by a body weight index greater than 25.
  • Obesity in the United States affects 20% of men and 25% of women. Patients with body weight index (BMI weight (kg) / height 2 (m 2 )) greater than or equal to 30 are considered obese (Int. J. Obes., 1998, 22, 39-47; Obesity Lancet , 1997, 350, 423-426). Obesity (BMI> 30) and overweight (25 ⁇ BMI ⁇ 30) can have several origins: they can occur as a result of dysregulation of food intake, hormonal dysregulation or even as a result administration of treatment: type II anti-diabetic treatment with sulfonylureas leads to weight gain in patients.
  • insulin therapy is also a source of body weight gain in patients (In Progress in Obesity Research, 8 th International Congress on Obesity, 1999, 739-746; Annals of Internai Medicine, 1998, 128, 165-175).
  • Obesity and overweight are well-established risk factors for cardiovascular disease: they are associated with a significant increase in the risks of stroke, non-insulin-dependent diabetes because they predispose to insulin resistance, dyslipidemia and the appearance of macrovascular diseases (nephropathies, retinopathies, angiopathies).
  • the combination according to the invention makes it possible to obtain a weight loss which even moderate significantly reduces all the risk factors associated with obesity (Int. J. Obes., 1997,
  • the combination according to the invention therefore finds its utility in the treatment and / or prevention of obesity and overweight characterized by a body weight index greater than 25.
  • the invention therefore relates to the use of the association between a derivative promoting lipid and carbohydrate metabolism and an antioxidant agent for obtaining pharmaceutical compositions intended for the treatment and / or prevention of obesity and characterized overweight by a body weight index greater than 25 and less than 30.
  • the combination according to the invention is useful in the treatment and / or prevention of obesity and overweight characterized by a body weight index greater than 25 and less than 30 induced by a therapeutic treatment, such as treatment of type I or II diabetes.
  • the invention therefore relates to the use of the association between a derivative promoting lipid and carbohydrate metabolism and an antioxidant agent for obtaining pharmaceutical compositions intended for the treatment and / or prevention of obesity and characterized overweight by a body weight index greater than 25 and less than 30 induced by a therapeutic treatment, such as the treatment of type I or II diabetes.
  • the invention also relates to pharmaceutical compositions containing the association between a derivative promoting lipid and carbohydrate metabolism and an antioxidant agent. as defined above in combination with one or more pharmaceutically acceptable excipients.
  • compositions according to the invention mention may be made more particularly of those which are suitable for oral, parenteral, nasal administration, simple or coated tablets, sublingual tablets, capsules, tablets, suppositories, creams, ointments , dermal gels, etc.
  • the invention relates to pharmaceutical compositions containing a compound of formula (I) as defined above and an antioxidant agent such as coenzyme Q ⁇ 0 or vitamin E in combination with one or more pharmaceutically acceptable excipients.
  • the dosage varies according to the sex, age and weight of the patient, the route of administration, the nature of the therapeutic indication or any associated treatments and ranges from 0.1 mg to 1 g of each component of association by 24 hours in one or more takes.
  • mice Male mice C57 Black 6 ob / ob from 8 to 12 weeks were used. After quarantining for one week, they were weighed and then randomized according to their weight, and 6 homogeneous groups (starting weight not significantly different) were formed. After being weighed, the different molecules to be tested are injected intraperitoneally once a day for 7 days. The molecules are injected into a 5% DMSO / 15% Solutol / Qsp H 2 O solution heated to 65 ° C to ensure good dissolution. The solution is further preheated before injection. The mice are weighed daily and the weight obtained after 7 days of treatment is noted.

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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)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Child & Adolescent Psychology (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)
EP05744511A 2004-03-31 2005-03-30 Kombination aus einer heterozyklischen verbindung und einem antioxidans und ihre verwendung zur behandlung von adipositas Withdrawn EP1729767A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0403359A FR2868313B1 (fr) 2004-03-31 2004-03-31 Nouvelle association entre un compose heterocyclique et un agent antioxydant et les compositions pharmaceutiques qui les contiennent
PCT/FR2005/000755 WO2005099694A1 (fr) 2004-03-31 2005-03-30 Association entre un compose heterocyclique et un agent antioxydant et son utilisation pour le traitement de l’obesite

Publications (1)

Publication Number Publication Date
EP1729767A1 true EP1729767A1 (de) 2006-12-13

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ID=34945535

Family Applications (1)

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EP05744511A Withdrawn EP1729767A1 (de) 2004-03-31 2005-03-30 Kombination aus einer heterozyklischen verbindung und einem antioxidans und ihre verwendung zur behandlung von adipositas

Country Status (19)

Country Link
US (1) US20070167502A1 (de)
EP (1) EP1729767A1 (de)
JP (1) JP2007530643A (de)
KR (1) KR100842567B1 (de)
CN (1) CN100536842C (de)
AR (1) AR048355A1 (de)
AU (1) AU2005232420B8 (de)
BR (1) BRPI0509389A (de)
CA (1) CA2563104A1 (de)
EA (1) EA012966B1 (de)
FR (1) FR2868313B1 (de)
GE (1) GEP20094637B (de)
HK (1) HK1099689A1 (de)
MA (1) MA28467B1 (de)
MY (1) MY142039A (de)
NO (1) NO20064858L (de)
UA (1) UA86801C2 (de)
WO (1) WO2005099694A1 (de)
ZA (1) ZA200607798B (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2894965B1 (fr) * 2005-12-20 2008-01-25 Servier Lab Nouveaux derives d'oximes heterocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR2898125B1 (fr) * 2006-03-06 2008-06-13 Servier Lab Nouveaux derives heterocycliques cycloalkyles, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994015595A1 (en) * 1993-01-06 1994-07-21 Jemo-Pharm A/S Medium comprising a pharmacological/biological active substance
DE10044805A1 (de) * 2000-09-11 2002-04-04 Martin Klingenberg Verwendung von Coenzym Q zur Regulierung der Funktion der Entkopplerproteine
WO2004032968A1 (fr) * 2002-10-11 2004-04-22 Les Laboratoires Servier Association entre un compose heterocyclique favorisant les metabolismes glucidiques et lipidiques et un agent antioxydant dans le traitement de l'obesite

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU748608B2 (en) * 1997-05-01 2002-06-06 Bristol-Myers Squibb Company MTP inhibitors and fat soluble vitamin therapeutic combinations to lower serum lipid levels
US6020383A (en) * 1999-01-11 2000-02-01 Eastman Chemicals Company Method for reducing blood cholesterol and/or blood triglycerides
FR2804431A1 (fr) * 2000-02-02 2001-08-03 Adir Nouveaux derives heterocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2002034259A1 (en) * 2000-10-26 2002-05-02 Fournier Laboratories Ireland Limited Combination of fenofibrate and coenzyme q10 for the treatment of endothelial dysfunction
JP2003116487A (ja) * 2001-10-15 2003-04-22 Beverly Corporation:Kk 痩身用食品

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994015595A1 (en) * 1993-01-06 1994-07-21 Jemo-Pharm A/S Medium comprising a pharmacological/biological active substance
DE10044805A1 (de) * 2000-09-11 2002-04-04 Martin Klingenberg Verwendung von Coenzym Q zur Regulierung der Funktion der Entkopplerproteine
WO2004032968A1 (fr) * 2002-10-11 2004-04-22 Les Laboratoires Servier Association entre un compose heterocyclique favorisant les metabolismes glucidiques et lipidiques et un agent antioxydant dans le traitement de l'obesite

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Monograph: Coenzyme Q10", ALTERNATIVE MEDICINE REVIEW, vol. 3, no. 1, 1998, pages 58 - 61 *

Also Published As

Publication number Publication date
NO20064858L (no) 2006-10-25
UA86801C2 (ru) 2009-05-25
JP2007530643A (ja) 2007-11-01
FR2868313A1 (fr) 2005-10-07
EA012966B1 (ru) 2010-02-26
AU2005232420B2 (en) 2009-02-19
US20070167502A1 (en) 2007-07-19
EA200601632A1 (ru) 2007-04-27
MY142039A (en) 2010-08-30
ZA200607798B (en) 2008-05-28
GEP20094637B (en) 2009-03-10
WO2005099694A8 (fr) 2006-11-09
HK1099689A1 (en) 2008-10-24
AR048355A1 (es) 2006-04-19
AU2005232420A1 (en) 2005-10-27
KR20060133073A (ko) 2006-12-22
KR100842567B1 (ko) 2008-07-01
CN1938024A (zh) 2007-03-28
CA2563104A1 (fr) 2005-10-27
AU2005232420B8 (en) 2009-06-11
MA28467B1 (fr) 2007-03-01
BRPI0509389A (pt) 2007-09-18
FR2868313B1 (fr) 2008-08-15
CN100536842C (zh) 2009-09-09
WO2005099694A1 (fr) 2005-10-27

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