WO2009007412A3 - Deglycation des ages - Google Patents

Deglycation des ages Download PDF

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Publication number
WO2009007412A3
WO2009007412A3 PCT/EP2008/058955 EP2008058955W WO2009007412A3 WO 2009007412 A3 WO2009007412 A3 WO 2009007412A3 EP 2008058955 W EP2008058955 W EP 2008058955W WO 2009007412 A3 WO2009007412 A3 WO 2009007412A3
Authority
WO
WIPO (PCT)
Prior art keywords
tissue
deglycation
age
substance
preventing
Prior art date
Application number
PCT/EP2008/058955
Other languages
English (en)
Other versions
WO2009007412A2 (fr
Inventor
Nabil Abdul-Malak
Cecile Altobelli
Eric Perrier
Original Assignee
Basf Beauty Care Solutions F
Nabil Abdul-Malak
Cecile Altobelli
Eric Perrier
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 Basf Beauty Care Solutions F, Nabil Abdul-Malak, Cecile Altobelli, Eric Perrier filed Critical Basf Beauty Care Solutions F
Priority to US12/668,061 priority Critical patent/US20100203175A1/en
Priority to CN200880101123A priority patent/CN101765432A/zh
Priority to JP2010515508A priority patent/JP2010533143A/ja
Priority to BRPI0813925-3A2A priority patent/BRPI0813925A2/pt
Priority to EP08786013A priority patent/EP2170358A2/fr
Publication of WO2009007412A2 publication Critical patent/WO2009007412A2/fr
Publication of WO2009007412A3 publication Critical patent/WO2009007412A3/fr

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803General methods of protein analysis not limited to specific proteins or families of proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/136Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/60Salicylic acid; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/347Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365Hydroxycarboxylic acids; Ketocarboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41Amines
    • A61K8/415Aminophenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A61K8/492Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/18Antioxidants, e.g. antiradicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Birds (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Dermatology (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Botany (AREA)
  • Diabetes (AREA)
  • Mycology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Cell Biology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Pathology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Biophysics (AREA)
  • General Physics & Mathematics (AREA)

Abstract

L'invention concerne l'utilisation comme ingrédient actif d'au moins une substance favorisant la déglycation des AGEs pour la préparation d'une composition, notamment pour limiter la présence des AGEs au niveau d'un tissu. L'invention concerne en particulier l'utilisation d'une telle substance pour la préparation d'une composition destinée à prévenir et/ou lutter contre la diminution de la flexibilité, et/ou de la plasticité, et/ou de l'élasticité, et/ou de la fonctionnalité d'un tissu, et/ou à prévenir et/ou lutter contre le vieillissement d'un tissu, en favorisant la déglycation des AGEs au niveau du tissu, ledit tissu étant de préférence la peau, ou la paroi tissulaire d'un vaisseau sanguin ou d'un organe.
PCT/EP2008/058955 2007-07-09 2008-07-09 Deglycation des ages WO2009007412A2 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US12/668,061 US20100203175A1 (en) 2007-07-09 2008-07-09 DEGLYCATION OF AGEs
CN200880101123A CN101765432A (zh) 2007-07-09 2008-07-09 Age的去糖化
JP2010515508A JP2010533143A (ja) 2007-07-09 2008-07-09 Ageの脱糖化
BRPI0813925-3A2A BRPI0813925A2 (pt) 2007-07-09 2008-07-09 Utilização de pelo menos uma substância favorecendo a reversão da reação de maillard frente aos ages, método de triagem de princípios ativos favorecendo a deglicação dos ages e composição.
EP08786013A EP2170358A2 (fr) 2007-07-09 2008-07-09 Deglycation des ages.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0756350 2007-07-09
FR0756350A FR2918570B1 (fr) 2007-07-09 2007-07-09 DIGLYCATION DES AGEs.

Publications (2)

Publication Number Publication Date
WO2009007412A2 WO2009007412A2 (fr) 2009-01-15
WO2009007412A3 true WO2009007412A3 (fr) 2009-04-02

Family

ID=39262794

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/058955 WO2009007412A2 (fr) 2007-07-09 2008-07-09 Deglycation des ages

Country Status (8)

Country Link
US (1) US20100203175A1 (fr)
EP (1) EP2170358A2 (fr)
JP (2) JP2010533143A (fr)
KR (1) KR20100047253A (fr)
CN (2) CN101765432A (fr)
BR (1) BRPI0813925A2 (fr)
FR (2) FR2918570B1 (fr)
WO (1) WO2009007412A2 (fr)

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FR2928548B1 (fr) * 2008-03-14 2015-07-03 Basf Beauty Care Solutions F Substances augmentant le seuil d'activation des cellules immunes
JP2010077123A (ja) * 2008-08-29 2010-04-08 Hayashikane Sangyo Kk メイラード反応阻害剤
FR2951085B1 (fr) * 2009-10-09 2012-05-18 Inst Substances Vegetales Utilisation de composes phenoliques pour la deglycation des proteines
FR2954702B1 (fr) 2009-12-31 2013-07-05 Basf Beauty Care Solutions F Agent stimulant l'expression de loxl
CN102883733B (zh) * 2010-02-10 2014-08-13 奥力榨油化株式会社 Age生成抑制剂
JP6012138B2 (ja) * 2010-10-04 2016-10-25 小林製薬株式会社 抗糖化剤
JP5855492B2 (ja) * 2012-02-27 2016-02-09 三省製薬株式会社 AGEs産生抑制剤
JP6054700B2 (ja) * 2012-10-10 2016-12-27 株式会社ノエビア 脱糖化剤及び皮膚外用剤
JP2015096488A (ja) * 2013-10-10 2015-05-21 康二 嘉島 終末糖化物質生成抑制方法
CN105770357A (zh) * 2015-10-16 2016-07-20 北京冠瑞金生物科技有限公司 蒜氨酸在制备抗抑郁症药物中的用途
JP2017088538A (ja) * 2015-11-10 2017-05-25 日本メナード化粧品株式会社 フィラグリン産生促進剤
KR102605628B1 (ko) * 2015-12-29 2023-11-22 주식회사 엘지생활건강 하스타토사이드를 포함하는 피부상태 개선용 조성물
CN114788791A (zh) 2017-06-23 2022-07-26 宝洁公司 用于改善皮肤外观的组合物和方法
JP2019214546A (ja) * 2018-06-11 2019-12-19 学校法人福岡大学 終末糖化産物生成抑制剤及び医薬組成物
CN112437657A (zh) 2018-07-03 2021-03-02 宝洁公司 处理皮肤状况的方法
CN109468370A (zh) * 2018-11-09 2019-03-15 广州益养生物科技有限公司 一种快速检测遗传性皮肤糖基化能力基因的方法
CN110684212A (zh) * 2019-10-31 2020-01-14 东南大学 一种仿贻贝的水下高粘性水凝胶的制备方法
US10959933B1 (en) 2020-06-01 2021-03-30 The Procter & Gamble Company Low pH skin care composition and methods of using the same
EP4157206A1 (fr) 2020-06-01 2023-04-05 The Procter & Gamble Company Méthode d'amélioration de la pénétration d'un composé de vitamine b3 dans la peau
CN112111020B (zh) * 2020-10-26 2022-07-19 无锡善元健康管理有限公司 桦树茸中抗糖成分的提取纯化及抗糖丸的制备方法
CN112370370B (zh) * 2020-11-19 2022-07-26 苏州禾研生物技术有限公司 一种氧糖双抗的组合物及其应用和氧糖双抗的产品
CN113876668B (zh) * 2021-11-16 2023-11-03 上海青颜博识生物技术有限公司 一种抗糖化植物来源组合物及其制备方法和在美容产品中的应用

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US20100203175A1 (en) 2010-08-12
JP2010533143A (ja) 2010-10-21
CN101765432A (zh) 2010-06-30
FR2918570B1 (fr) 2012-10-05
EP2170358A2 (fr) 2010-04-07
FR2918570A1 (fr) 2009-01-16
FR2975495A1 (fr) 2012-11-23
BRPI0813925A2 (pt) 2014-12-30
JP2014028814A (ja) 2014-02-13

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