CN104507951B - 诱导骨生成和hedgehog信号传导且抑制脂肪形成的氧固醇类似物氧固醇化合物149 - Google Patents

诱导骨生成和hedgehog信号传导且抑制脂肪形成的氧固醇类似物氧固醇化合物149 Download PDF

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Publication number
CN104507951B
CN104507951B CN201380033489.6A CN201380033489A CN104507951B CN 104507951 B CN104507951 B CN 104507951B CN 201380033489 A CN201380033489 A CN 201380033489A CN 104507951 B CN104507951 B CN 104507951B
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compound
oxysterol
bone
oxysterol compound
purposes
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Expired - Fee Related
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CN201380033489.6A
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Chinese (zh)
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CN104507951A (zh
Inventor
F.帕哈米
M.E.琼格
F.斯塔彭贝克
小威廉.M.皮尔斯
K.G.泰勒
K.E.默滕
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University of Louisville Research Foundation ULRF
University of California San Diego UCSD
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University of Louisville Research Foundation ULRF
University of California San Diego UCSD
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K33/16—Fluorine compounds
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1875—Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
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    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
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    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0654—Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/38—Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/40—Regulators of development
    • C12N2501/41—Hedgehog proteins; Cyclopamine (inhibitor)
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    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
    • C12N2506/1346—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from mesenchymal stem cells
    • C12N2506/1353—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from mesenchymal stem cells from bone marrow mesenchymal stem cells (BM-MSC)

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CN201380033489.6A 2012-05-07 2013-03-15 诱导骨生成和hedgehog信号传导且抑制脂肪形成的氧固醇类似物氧固醇化合物149 Expired - Fee Related CN104507951B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261643776P 2012-05-07 2012-05-07
US61/643,776 2012-05-07
PCT/US2013/032650 WO2013169397A1 (en) 2012-05-07 2013-03-15 Novel oxysterol analogue, oxy149, induces osteogenesis and hedgehog signaling and inhibits adipogenesis

Publications (2)

Publication Number Publication Date
CN104507951A CN104507951A (zh) 2015-04-08
CN104507951B true CN104507951B (zh) 2016-09-07

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CN201380033489.6A Expired - Fee Related CN104507951B (zh) 2012-05-07 2013-03-15 诱导骨生成和hedgehog信号传导且抑制脂肪形成的氧固醇类似物氧固醇化合物149

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Country Link
US (1) US20150140059A1 (enExample)
EP (1) EP2847205A4 (enExample)
JP (1) JP2015517493A (enExample)
KR (1) KR20150008160A (enExample)
CN (1) CN104507951B (enExample)
AU (1) AU2013260057A1 (enExample)
CA (1) CA2872734A1 (enExample)
IN (1) IN2014DN09804A (enExample)
RU (1) RU2014149153A (enExample)
WO (1) WO2013169397A1 (enExample)

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CA2643732C (en) 2006-02-27 2012-08-21 The Regents Of The University Of California Oxysterol compounds and the hedgehog pathway
JP2011505357A (ja) 2007-12-03 2011-02-24 ザ リージェンツ オブ ザ ユニバーシティー オブ カリフォルニア ヘッジホッグシグナル伝達、骨誘導、抗脂肪生成、及びｗｎｔシグナル伝達を活性するためのオキシステロール
WO2013169399A1 (en) 2012-05-07 2013-11-14 The Regents Of The University Of California Oxysterol analogue oxy133 induces osteogenesis and hedgehog signaling and inhibits adipogenesis
WO2014179756A1 (en) * 2013-05-02 2014-11-06 The Regents Of The University Of California Bone-selective osteogenic oxysterol-bone targeting agents
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CN107427526B (zh) 2014-12-09 2021-08-03 华沙整形外科股份有限公司 涉及甾醇的化合物和方法
US10632230B2 (en) 2015-07-10 2020-04-28 Warsaw Orthopedic, Inc. Implants having a high drug load of an oxysterol and methods of use
US12171909B2 (en) 2015-07-10 2024-12-24 Warsaw Orthopedic, Inc. Implants having a drug load of an oxysterol and methods of use
US9637514B1 (en) * 2015-10-26 2017-05-02 MAX BioPharma, Inc. Oxysterols and hedgehog signaling
US20170275330A1 (en) * 2016-03-28 2017-09-28 Warsaw Orthopedic, Inc. Polymorphic forms of an oxysterol and methods of making them
US9987290B2 (en) * 2016-03-28 2018-06-05 Warsaw Orthopedic, Inc. Methods for the separation and detection of an oxysterol
US10688222B2 (en) 2016-11-21 2020-06-23 Warsaw Orthopedic, Inc. Lyophilized moldable implants containing an oxysterol
US11384114B2 (en) * 2016-12-09 2022-07-12 Warsaw Orthopedic, Inc. Polymorphic forms of an oxysterol and methods of making them
US10294264B2 (en) * 2017-04-21 2019-05-21 Warsaw Orthopedic, Inc. Oxysterol-therapeutic agent derivative for bone healing
US10434106B2 (en) 2017-05-19 2019-10-08 Warsaw Orthopedic, Inc. Oxysterol-statin compounds for bone growth
US11464888B2 (en) 2017-06-12 2022-10-11 Warsaw Orthopedic, Inc. Moldable formulations containing an oxysterol in an acellular tissue matrix
WO2019048898A1 (en) 2017-09-05 2019-03-14 INSERM (Institut National de la Santé et de la Recherche Médicale) PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF ENDOTHELIAL DYSFUNCTION
EP3833377B1 (en) * 2018-08-10 2023-11-22 Alexion Pharmaceuticals, Inc. Bone healing at implants using alkaline phosphatase
BR112023016048A2 (pt) 2021-02-12 2023-11-14 Alexion Pharma Inc Polipeptídeos de fosfatase alcalina e métodos de uso dos mesmos

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WO2013169397A1 (en) 2013-11-14
EP2847205A4 (en) 2016-01-20
HK1208871A1 (en) 2016-03-18
US20150140059A1 (en) 2015-05-21
RU2014149153A (ru) 2016-06-27
AU2013260057A1 (en) 2014-11-27
IN2014DN09804A (enExample) 2015-07-31
EP2847205A1 (en) 2015-03-18
KR20150008160A (ko) 2015-01-21
JP2015517493A (ja) 2015-06-22
CA2872734A1 (en) 2013-11-14
CN104507951A (zh) 2015-04-08

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