BR112013030605A2 - formulações orais de antioxidantes direcionados mitocondrialmente e preparação e uso dos mesmos - Google Patents

formulações orais de antioxidantes direcionados mitocondrialmente e preparação e uso dos mesmos

Info

Publication number
BR112013030605A2
BR112013030605A2 BR112013030605A BR112013030605A BR112013030605A2 BR 112013030605 A2 BR112013030605 A2 BR 112013030605A2 BR 112013030605 A BR112013030605 A BR 112013030605A BR 112013030605 A BR112013030605 A BR 112013030605A BR 112013030605 A2 BR112013030605 A2 BR 112013030605A2
Authority
BR
Brazil
Prior art keywords
preparation
antioxidants
oral formulations
directed
mitochondrially
Prior art date
Application number
BR112013030605A
Other languages
English (en)
Portuguese (pt)
Inventor
Alexander A Andreev-Andrievsky
Andrey A Zamyatnin
Eugeny S Efremov
Lawrence T Friedhoff
Maxim V Egorov
Maxim V Skulachev
Olga Y Pletushkina
Roman A Zinovkin
Tatiana V Zinevich
Vadim N Tashlitsky
Vladimir P Skulachev
Original Assignee
Mitotech Sa
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 Mitotech Sa filed Critical Mitotech Sa
Publication of BR112013030605A2 publication Critical patent/BR112013030605A2/pt

Links

Classifications

    • 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
    • A61K31/047Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/12Ketones
    • A61K31/122Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/545Heterocyclic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/548Phosphates or phosphonates, e.g. bone-seeking
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0087Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P39/00General protective or antinoxious agents
    • A61P39/06Free radical scavengers or antioxidants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/54Quaternary phosphonium compounds
    • C07F9/5435Cycloaliphatic phosphonium compounds
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/54Quaternary phosphonium compounds
    • C07F9/5442Aromatic phosphonium compounds (P-C aromatic linkage)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02Phosphorus compounds
    • C07F9/28Phosphorus compounds with one or more P—C bonds
    • C07F9/54Quaternary phosphonium compounds
    • C07F9/5456Arylalkanephosphonium compounds
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09BORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B11/00Diaryl- or thriarylmethane dyes
    • C09B11/04Diaryl- or thriarylmethane dyes derived from triarylmethanes, i.e. central C-atom is substituted by amino, cyano, alkyl
    • C09B11/10Amino derivatives of triarylmethanes
    • C09B11/24Phthaleins containing amino groups ; Phthalanes; Fluoranes; Phthalides; Rhodamine dyes; Phthaleins having heterocyclic aryl rings; Lactone or lactame forms of triarylmethane dyes
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09BORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B57/00Other synthetic dyes of known constitution
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09BORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B69/00Dyes not provided for by a single group of this subclass
    • C09B69/001Dyes containing an onium group attached to the dye skeleton via a bridge

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Inorganic Chemistry (AREA)
  • Rheumatology (AREA)
  • Biophysics (AREA)
  • Emergency Medicine (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Dermatology (AREA)
  • Obesity (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
BR112013030605A 2011-06-03 2012-06-04 formulações orais de antioxidantes direcionados mitocondrialmente e preparação e uso dos mesmos BR112013030605A2 (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161492940P 2011-06-03 2011-06-03
PCT/US2012/040711 WO2012167236A1 (en) 2011-06-03 2012-06-04 Oral formulations of mitochondrially-targeted antioxidants and their preparation and use

Publications (1)

Publication Number Publication Date
BR112013030605A2 true BR112013030605A2 (pt) 2016-12-13

Family

ID=47259946

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112013030605A BR112013030605A2 (pt) 2011-06-03 2012-06-04 formulações orais de antioxidantes direcionados mitocondrialmente e preparação e uso dos mesmos

Country Status (10)

Country Link
US (2) US9192676B2 (https=)
EP (1) EP2714024B1 (https=)
JP (2) JP6448366B2 (https=)
CN (1) CN103764132B (https=)
AU (1) AU2012261854B2 (https=)
BR (1) BR112013030605A2 (https=)
CA (1) CA2837437C (https=)
EA (1) EA031399B1 (https=)
ES (1) ES2704064T3 (https=)
WO (1) WO2012167236A1 (https=)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012167236A1 (en) * 2011-06-03 2012-12-06 Mitotech Sa Oral formulations of mitochondrially-targeted antioxidants and their preparation and use
EA031799B1 (ru) * 2013-01-22 2019-02-28 Ооо Митотех Способ лечения воспалительного расстройства при помощи антиоксиданта, направленного на митохондрии
EP3030267A2 (en) * 2013-04-11 2016-06-15 Mitotech SA Mitochondrially-targeted timoquinones and toluquinones
WO2015162494A2 (en) 2014-02-25 2015-10-29 Mitotech, S.A. Cosmetic compositions of mitochonrially targeted antioxidants
WO2019139831A1 (en) * 2018-01-10 2019-07-18 Dana-Farber Cancer Institute, Inc. Methods for identification, assessment, prevention, and treatment of metabolic disorders using succinate
CN115551476A (zh) * 2019-12-10 2022-12-30 米陀科技有限公司 用于线粒体靶向抗氧化剂的不同组合物的聚合物基质
WO2021198786A1 (en) * 2020-04-03 2021-10-07 Mitotech S.A. Use of mitochondria-targeted antioxidants to treat severe inflammatory conditions
CN114344274A (zh) * 2022-01-05 2022-04-15 盖茨汉普(武汉)植物应用研究有限公司 一种Mitoq抗氧化硬胶囊配方及制备工艺
WO2025078880A1 (en) * 2023-10-11 2025-04-17 Mitotech S.A. Mitochondria-targeted antioxidants for use in the treatment of cell balloooning-associated diseases, such as non-alcoholic fatty liver disease (nafld) and non-alcoholic steatohepatitis (nash)

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US5538974A (en) 1994-01-27 1996-07-23 Senju Pharamceutical Co., Ltd. Ophthalmic composition for lowering intraocular pressure
NZ505352A (en) 1997-11-25 2002-12-20 Univ Otago Mitochondrially targeted antioxidants
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US20080275005A1 (en) 1998-11-25 2008-11-06 Murphy Michael P Mitochondrially targeted antioxidants
US20070270381A1 (en) 2000-05-25 2007-11-22 Antipodean Pharmaceuticals, Inc. Mitochondrially targeted antioxidants
US20020044913A1 (en) 2000-02-11 2002-04-18 Hamilton Nathan D. Cosmetics to support skin metabolism
ITRM20010755A1 (it) 2001-12-20 2003-06-20 Simonelli Giuseppe Uso del chinone q10 per il trattamento delle malattie oculari.
US6984636B2 (en) 2002-08-12 2006-01-10 Medical Research Council Mitochondrially targeted antioxidants
WO2005033092A1 (en) 2003-09-19 2005-04-14 Galileo Pharmaceuticals, Inc. Chroman derivatives
CN1997403A (zh) 2004-07-13 2007-07-11 奥里迪斯生物医学研究及开发有限责任公司 靶向线粒体的抗氧化剂在治疗肝病和上皮癌中的用途
WO2006025247A1 (ja) * 2004-08-30 2006-03-09 Kaneka Corporation ミトコンドリア賦活剤
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EP2119436A4 (en) 2006-10-20 2010-03-03 Ltd Liability Company Mitotech PHARMACEUTICAL COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF EYE DISEASES
WO2008048135A1 (fr) 2006-10-20 2008-04-24 Limited Liability Company 'mitotechnology' Composition destinée à la régénération, la stimulation de la croissance et l'adaptation de plantes à tous types de facteurs de stress
EP2145623A4 (en) * 2007-01-29 2010-10-27 Ltd Liability Company Mitotech PHARMACEUTICAL AND COSMETIC COMPOSITIONS FOR ACCELERATING THE PROCESS OF WOUND HEALING AND OTHER SURFACE INJURIES
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WO2012167236A1 (en) * 2011-06-03 2012-12-06 Mitotech Sa Oral formulations of mitochondrially-targeted antioxidants and their preparation and use

Also Published As

Publication number Publication date
EP2714024A1 (en) 2014-04-09
CN103764132B (zh) 2017-04-12
AU2012261854B2 (en) 2017-11-16
CA2837437C (en) 2020-12-15
CA2837437A1 (en) 2012-12-06
EP2714024B1 (en) 2018-10-03
EA201301321A1 (ru) 2014-11-28
EP2714024A4 (en) 2014-12-31
EA031399B1 (ru) 2018-12-28
US9192676B2 (en) 2015-11-24
US20160038603A1 (en) 2016-02-11
US9572890B2 (en) 2017-02-21
ES2704064T3 (es) 2019-03-14
WO2012167236A1 (en) 2012-12-06
JP6448366B2 (ja) 2019-01-09
US20150025043A1 (en) 2015-01-22
JP2014515407A (ja) 2014-06-30
JP6461276B2 (ja) 2019-01-30
CN103764132A (zh) 2014-04-30
JP2018035182A (ja) 2018-03-08

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