ES2675720T3 - Inhibidores de quinasa no selectivos - Google Patents
Inhibidores de quinasa no selectivos Download PDFInfo
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- ES2675720T3 ES2675720T3 ES14737648.7T ES14737648T ES2675720T3 ES 2675720 T3 ES2675720 T3 ES 2675720T3 ES 14737648 T ES14737648 T ES 14737648T ES 2675720 T3 ES2675720 T3 ES 2675720T3
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- A61P7/06—Antianaemics
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
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- Obesity (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Tropical Medicine & Parasitology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
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- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US201361751217P | 2013-01-10 | 2013-01-10 | |
| US201361751217P | 2013-01-10 | ||
| US201361889887P | 2013-10-11 | 2013-10-11 | |
| US201361889887P | 2013-10-11 | ||
| PCT/US2014/010778 WO2014110200A1 (en) | 2013-01-10 | 2014-01-09 | Non-selective kinase inhibitors |
Publications (1)
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| ES2675720T3 true ES2675720T3 (es) | 2018-07-12 |
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| ES14737648.7T Active ES2675720T3 (es) | 2013-01-10 | 2014-01-09 | Inhibidores de quinasa no selectivos |
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| US (3) | US9815815B2 (enExample) |
| EP (1) | EP3007689B1 (enExample) |
| JP (2) | JP6387488B2 (enExample) |
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| CA (1) | CA2897651C (enExample) |
| DK (1) | DK3007689T3 (enExample) |
| ES (1) | ES2675720T3 (enExample) |
| WO (1) | WO2014110200A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2897651C (en) * | 2013-01-10 | 2021-09-21 | Pulmokine, Inc. | Non-selective kinase inhibitors |
| EP2988738A4 (en) * | 2013-01-10 | 2016-11-09 | Pulmokine Inc | THERAPEUTIC INDICATIONS OF KINASE INHIBITORS |
| HK1213251A1 (zh) | 2013-03-14 | 2016-06-30 | Novartis Ag | 作为突变idh抑制剂的3-嘧啶-4-基-恶唑烷-2-酮化合物 |
| US20150044288A1 (en) * | 2013-07-31 | 2015-02-12 | Windward Pharma, Inc. | Aerosol tyrosine kinase inhibitor compounds and uses thereof |
| CA2926793C (en) * | 2013-10-11 | 2022-11-22 | Lawrence S. ZISMAN | Spray-dry formulations for treating pulmonary arterial hypertension |
| CN110087653A (zh) * | 2016-10-27 | 2019-08-02 | 普尔莫凯恩股份有限公司 | 用于治疗肺高血压的组合疗法 |
| CN110573878A (zh) * | 2017-03-16 | 2019-12-13 | 小利兰·斯坦福大学托管委员会 | 用于kras阳性癌症的诊断和治疗方法 |
| US20210038510A1 (en) * | 2018-02-08 | 2021-02-11 | Pulmokine, Inc. | Formulations of kinase inhibitors and prostanoids |
| CN109574296B (zh) * | 2018-11-27 | 2021-05-07 | 合肥工业大学 | 一种从含蟹肉蛋白废水中回收蛋白的方法 |
| JP2022532431A (ja) | 2019-05-16 | 2022-07-14 | エアロベイト セラピューティクス， インコーポレイテッド | イマチニブ製剤、その製造および使用 |
| US11464776B2 (en) | 2019-05-16 | 2022-10-11 | Aerovate Therapeutics, Inc. | Inhalable imatinib formulations, manufacture, and uses thereof |
| US20240228462A1 (en) * | 2021-05-07 | 2024-07-11 | Gb002, Inc. | Crystalline forms of n-{3-[(1s)-1-{[6-(3,4-dimethoxyphenyl)pyrazin-2- yl]amino}ethyl]phenyl}-5-methylpyridine-3-carboxamide and related products and methods |
| KR20240115979A (ko) | 2021-11-08 | 2024-07-26 | 프로젠토스 테라퓨틱스, 인크. | 혈소판-유래 성장 인자 수용체(pdgfr) 알파 억제제 및 이의 용도 |
| CN119677525A (zh) | 2022-08-10 | 2025-03-21 | Gb002股份有限公司 | 用于治疗动脉性肺动脉高压（pah）的酪氨酸激酶抑制剂和激活素2型受体拮抗剂的组合疗法 |
| CN119930631B (zh) * | 2025-04-07 | 2025-06-24 | 山东大学 | 一种靶向ddr1受体的化合物及其衍生的放射性示踪剂 |
Family Cites Families (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4118401A (en) | 1977-10-19 | 1978-10-03 | American Hoechst Corporation | Preparation of 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acid and precursors therefor |
| JPS5488231A (en) | 1977-12-22 | 1979-07-13 | Sumitomo Chem Co Ltd | 3-phenyloxymethylaniline derivative, its preparation, and herbicides consisting of it |
| US4570630A (en) | 1983-08-03 | 1986-02-18 | Miles Laboratories, Inc. | Medicament inhalation device |
| DE3632329A1 (de) | 1986-09-24 | 1988-03-31 | Bayer Ag | Substituierte phenylsulfonamide |
| US5648369A (en) | 1991-11-20 | 1997-07-15 | University Of Kentucky Research Foundation | Aminoalkylpyridine compounds which are useful as anitconvulsant drugs, excitatory amino acid inhibitors and NMDA sigma receptor antagonists |
| SK27198A3 (en) | 1995-08-30 | 1998-09-09 | Bayer Ag | Acylaminosalicylic acid amides and their uses as pesticides |
| JPH09268169A (ja) | 1996-04-01 | 1997-10-14 | Otsuka Chem Co Ltd | サリチル酸アニリド誘導体、それを有効成分として含む植物病害防除剤 |
| ATE364374T1 (de) | 1997-08-11 | 2007-07-15 | Pfizer Prod Inc | Feste pharmazeutische dispersionen mit erhöhter bioverfügbarkeit |
| US6015815A (en) | 1997-09-26 | 2000-01-18 | Abbott Laboratories | Tetrazole-containing rapamycin analogs with shortened half-lives |
| CA2382821A1 (en) | 1999-08-25 | 2001-03-01 | Advanced Inhalation Research, Inc. | Modulation of release from dry powder formulations |
| US6458849B1 (en) | 1999-09-23 | 2002-10-01 | G.D. Searle & Co. | use of substituted N,N-disubstituted mercapto amino compounds for inhibiting cholesteryl ester transfer protein activity |
| HUP0203323A3 (en) | 1999-10-19 | 2004-01-28 | Merck & Co Inc | Tyrosine kinase inhibitors and pharmaceutical compositions containing them |
| WO2001028993A2 (en) | 1999-10-19 | 2001-04-26 | Merck & Co. Inc. | Tyrosine kinase inhibitors |
| HN2001000008A (es) | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
| US6420382B2 (en) | 2000-02-25 | 2002-07-16 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| JP2003523390A (ja) | 2000-02-25 | 2003-08-05 | メルク エンド カムパニー インコーポレーテッド | チロシンキナーゼ阻害薬 |
| WO2002060492A1 (en) | 2001-01-30 | 2002-08-08 | Cytopia Pty Ltd | Methods of inhibiting kinases |
| US6825198B2 (en) | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
| US7122550B2 (en) | 2002-05-23 | 2006-10-17 | Cytopia Pty Ltd | Protein kinase inhibitors |
| CA2486187C (en) | 2002-05-23 | 2013-02-19 | Cytopia Pty Ltd. | Kinase inhibitors |
| AUPS251502A0 (en) * | 2002-05-23 | 2002-06-13 | Cytopia Pty Ltd | Protein kinase inhibitors |
| US6776309B2 (en) | 2002-05-23 | 2004-08-17 | Ben Z. Cohen | Medically accurate pump system |
| TW200410688A (en) | 2002-06-26 | 2004-07-01 | Ono Pharmaceutical Co | Therapeutics for diseases from vasoconstriction or vasodilatation |
| EP1545523A1 (en) | 2002-07-03 | 2005-06-29 | Astex Technology Limited | 3-&-grave;(HETERO) ARYLMETHOXY ! PYRIDINES AND THEIR ANALOGUES ASP38 MAP KINASE INHIBITORS |
| WO2004006858A2 (en) | 2002-07-15 | 2004-01-22 | Myriad Genetics, Inc | Compounds, compositions, and methods employing same |
| AU2003272007A1 (en) | 2002-10-25 | 2004-05-13 | The Administrators Of The Tulane Educational Fund | Use of n-5-4-(4-methylpiperaziomethyl)-benzoylamido!-2-methylphenyl!-4-(3-pyridyl)2-pyridine-amine for the treatment of pulmonary hypertension |
| AU2002953255A0 (en) | 2002-12-11 | 2003-01-02 | Cytopia Research Pty Ltd | Protein kinase inhibitors |
| WO2005002673A1 (en) | 2003-07-03 | 2005-01-13 | Astex Therapeutics Limited | Raf kinase inhibitors |
| US20050026879A1 (en) | 2003-07-31 | 2005-02-03 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a tyrosine kinase inhibitor, delta opioid receptor antagonist, neurokinin receptor antagonist, or VCAM inhibitor for treatment of asthma or chronic obstructive pulmonary disease |
| AR045731A1 (es) | 2003-08-06 | 2005-11-09 | Vertex Pharma | Compuestos de aminotriazol utiles como inhibidores de quinasas de proteinas |
| KR101167573B1 (ko) | 2003-11-07 | 2012-07-30 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 개선된 약학적 성질을 갖는 퀴놀리논 화합물의 약학적으로허용가능한 염 |
| JP4808628B2 (ja) * | 2003-12-03 | 2011-11-02 | ワイエム・バイオサイエンシズ・オーストラリア・ピーティーワイ・リミテッド | アゾール系キナーゼ阻害剤 |
| ATE497949T1 (de) | 2003-12-03 | 2011-02-15 | Ym Biosciences Australia Pty | Tubulininhibitoren |
| GB2432834A (en) | 2004-01-12 | 2007-06-06 | Cytopia Res Pty Ltd | Selective Kinase Inhibitors |
| WO2005114219A2 (en) | 2004-05-20 | 2005-12-01 | Wyeth | Assays to identify irreversibly binding inhibitors of receptor tyrosine kinases |
| JP2006111553A (ja) | 2004-10-13 | 2006-04-27 | Dainippon Sumitomo Pharma Co Ltd | スルホニルオキシインドール誘導体及びそれを含有する医薬組成物 |
| JP5075832B2 (ja) | 2005-11-10 | 2012-11-21 | バイエル・ファルマ・アクチェンゲゼルシャフト | 肺高血圧を処置するためのジアリールウレア |
| WO2007087575A2 (en) | 2006-01-24 | 2007-08-02 | University Of Chicago | Compositions and methods for treating pulmonary hypertension |
| AU2007220047B2 (en) | 2006-02-28 | 2013-08-01 | Ym Biosciences Australia Pty Ltd | Inhibition of JAK2 as a treatment of pulmonary arterial hypertension |
| WO2007124382A2 (en) | 2006-04-19 | 2007-11-01 | Novartis Vaccines And Diagnostics, Inc. | Inhaled imipenem |
| EP3048099A3 (en) * | 2006-11-15 | 2016-09-21 | YM BioSciences Australia Pty Ltd | Inhibitors of kinase activity |
| BRPI0811617A2 (pt) | 2007-05-04 | 2017-06-06 | Irm Llc | derivados de primidina e composições como inibidores de c-kit e pdgfr quinase. |
| EP2152688A1 (en) | 2007-05-04 | 2010-02-17 | Irm Llc | Compounds and compositions as c-kit and pdgfr kinase inhibitors |
| MX2010002004A (es) | 2007-08-22 | 2010-03-11 | Irm Llc | Compuestos de 5-(4-(halo-alcoxi)-fenil)-pirimidin-2-amina y composiciones con inhibidores de cinasa. |
| WO2009026204A1 (en) | 2007-08-22 | 2009-02-26 | Irm Llc | 2-heteroarylamino-pyrimidine derivatives as kinase inhibitors |
| MX2010006033A (es) | 2007-12-20 | 2010-07-16 | Bayer Schering Pharma Ag | 4-(4-ciano-2-tioaril)dihidropirimidinonas y su uso. |
| CA2732789A1 (en) | 2008-08-13 | 2010-02-18 | Novartis Ag | Treatment of pulmonary arterial hypertension |
| DE102009004197A1 (de) | 2009-01-09 | 2010-07-15 | Bayer Schering Pharma Aktiengesellschaft | Heterocyclisch anellierte Diaryldihydropyrimidin-Derivate und ihre Verwendung |
| WO2010102066A1 (en) | 2009-03-05 | 2010-09-10 | Bend Research, Inc. | Dextran polymer powder for inhalation administration of pharmaceuticals |
| WO2010132827A1 (en) | 2009-05-15 | 2010-11-18 | Bend Research, Inc. | Low-molecular dextran for powder inhalations |
| TWI625121B (zh) | 2009-07-13 | 2018-06-01 | 基利科學股份有限公司 | 調節細胞凋亡信號之激酶的抑制劑 |
| US9084976B2 (en) | 2010-09-03 | 2015-07-21 | Bend Research, Inc. | Spray-drying apparatus and methods of using the same |
| EP2618924A1 (en) | 2010-09-24 | 2013-07-31 | Bend Research, Inc. | High-temperature spray drying process and apparatus |
| JOP20120023B1 (ar) | 2011-02-04 | 2022-03-14 | Novartis Ag | صياغات مساحيق جافة من جسيمات تحتوي على واحد أو اثنين من المواد الفعالة لعلاج امراض ممرات الهواء الانسدادية او الالتهابية |
| JP6012716B2 (ja) | 2011-05-19 | 2016-10-25 | サヴァラ，インク． | 乾燥粉末バンコマイシン組成物および関連する方法 |
| US9199981B2 (en) | 2011-09-01 | 2015-12-01 | Novartis Ag | Compounds and compositions as C-kit kinase inhibitors |
| WO2013033167A1 (en) | 2011-09-01 | 2013-03-07 | Irm Llc | Compounds and compositions as c-kit kinase inhibitors |
| EP2988738A4 (en) * | 2013-01-10 | 2016-11-09 | Pulmokine Inc | THERAPEUTIC INDICATIONS OF KINASE INHIBITORS |
| CA2897651C (en) | 2013-01-10 | 2021-09-21 | Pulmokine, Inc. | Non-selective kinase inhibitors |
| US20150044288A1 (en) | 2013-07-31 | 2015-02-12 | Windward Pharma, Inc. | Aerosol tyrosine kinase inhibitor compounds and uses thereof |
| CA2926793C (en) | 2013-10-11 | 2022-11-22 | Lawrence S. ZISMAN | Spray-dry formulations for treating pulmonary arterial hypertension |
| WO2015179369A1 (en) | 2014-05-20 | 2015-11-26 | Infinity Pharmaceuticals, Inc. | Treatment of pulmonary or respiratory diseases by inhalation administration of pi3 kinase inhibitors |
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2014
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- 2014-01-09 AU AU2014205483A patent/AU2014205483B2/en active Active
- 2014-01-09 DK DK14737648.7T patent/DK3007689T3/en active
- 2014-01-09 ES ES14737648.7T patent/ES2675720T3/es active Active
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- 2014-01-09 CN CN201480010529.XA patent/CN105142624A/zh active Pending
- 2014-01-09 CN CN201811323814.3A patent/CN109568319A/zh active Pending
- 2014-01-09 WO PCT/US2014/010778 patent/WO2014110200A1/en not_active Ceased
- 2014-01-09 JP JP2015552757A patent/JP6387488B2/ja active Active
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2017
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2018
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2019
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2020
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2024
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| AU2014205483B2 (en) | 2017-11-30 |
| AU2023201605A1 (en) | 2023-04-13 |
| US10246438B2 (en) | 2019-04-02 |
| US9815815B2 (en) | 2017-11-14 |
| CN109568319A (zh) | 2019-04-05 |
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| JP6387488B2 (ja) | 2018-09-12 |
| EP3007689A4 (en) | 2016-07-13 |
| CA2897651C (en) | 2021-09-21 |
| US20150353527A1 (en) | 2015-12-10 |
| AU2024259702A1 (en) | 2024-11-21 |
| EP3007689A1 (en) | 2016-04-20 |
| AU2018201406A1 (en) | 2018-03-15 |
| WO2014110200A1 (en) | 2014-07-17 |
| AU2020289802A1 (en) | 2021-01-21 |
| US20190248761A1 (en) | 2019-08-15 |
| JP2018158931A (ja) | 2018-10-11 |
| AU2023201605B2 (en) | 2024-08-29 |
| JP2016506418A (ja) | 2016-03-03 |
| CA2897651A1 (en) | 2014-07-17 |
| EP3007689B1 (en) | 2018-03-07 |
| DK3007689T3 (en) | 2018-06-14 |
| US20180162837A1 (en) | 2018-06-14 |
| AU2014205483A1 (en) | 2015-08-27 |
| JP6547042B2 (ja) | 2019-07-17 |
| CN105142624A (zh) | 2015-12-09 |
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