JP6617104B2 - ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩 - Google Patents

５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩 Download PDF

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JP6617104B2
JP6617104B2 JP2016533926A JP2016533926A JP6617104B2 JP 6617104 B2 JP6617104 B2 JP 6617104B2 JP 2016533926 A JP2016533926 A JP 2016533926A JP 2016533926 A JP2016533926 A JP 2016533926A JP 6617104 B2 JP6617104 B2 JP 6617104B2
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hemisulfate
thf
pharmaceutical composition
cancer
methylene
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JP2016528242A (ja
JP2016528242A5 (enExample
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モーザー・ルードルフ
グレーン・ヴィオーラ
エッガー・トーマス
アマン・トーマス
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メルク・アンド・コンパニー
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    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • C07D487/14—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • 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
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems
    • C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
    • C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems
    • C07D475/12—Heterocyclic compounds containing pteridine ring systems containing pteridine ring systems condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems
    • C07D475/12—Heterocyclic compounds containing pteridine ring systems containing pteridine ring systems condensed with carbocyclic rings or ring systems
    • C07D475/14—Benz [g] pteridines, e.g. riboflavin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Steroid Compounds (AREA)
JP2016533926A 2013-08-14 2014-08-14 ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩 Active JP6617104B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP13004050.4A EP2837631A1 (en) 2013-08-14 2013-08-14 New stable salt of 5,10-methylene-(6R)-tetrahydrofolic acid
EP13004050.4 2013-08-14
PCT/EP2014/067447 WO2015022407A1 (en) 2013-08-14 2014-08-14 Hemisulfate salt of 5,10-methylene-(6r)-tetrahydrofolic acid

Related Child Applications (2)

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JP2018164332A Division JP6735321B2 (ja) 2013-08-14 2018-09-03 ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩
JP2019070293A Division JP6764501B2 (ja) 2013-08-14 2019-04-02 ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩

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JP2016528242A JP2016528242A (ja) 2016-09-15
JP2016528242A5 JP2016528242A5 (enExample) 2017-12-14
JP6617104B2 true JP6617104B2 (ja) 2019-12-04

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JP2016533926A Active JP6617104B2 (ja) 2013-08-14 2014-08-14 ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩
JP2018164332A Active JP6735321B2 (ja) 2013-08-14 2018-09-03 ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩
JP2019070293A Active JP6764501B2 (ja) 2013-08-14 2019-04-02 ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩
JP2020083208A Active JP7396960B2 (ja) 2013-08-14 2020-05-11 ５，１０－メチレン－（６ｒ）－テトラヒドロ葉酸のヘミ硫酸塩
JP2021183793A Active JP7710356B2 (ja) 2013-08-14 2021-11-11 ５，１０－メチレン－（６ｒ）－テトラヒドロ葉酸のヘミ硫酸塩

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JP2019070293A Active JP6764501B2 (ja) 2013-08-14 2019-04-02 ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩
JP2020083208A Active JP7396960B2 (ja) 2013-08-14 2020-05-11 ５，１０－メチレン－（６ｒ）－テトラヒドロ葉酸のヘミ硫酸塩
JP2021183793A Active JP7710356B2 (ja) 2013-08-14 2021-11-11 ５，１０－メチレン－（６ｒ）－テトラヒドロ葉酸のヘミ硫酸塩

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US (4) US20160185787A1 (enExample)
EP (3) EP2837631A1 (enExample)
JP (5) JP6617104B2 (enExample)
KR (2) KR102410373B1 (enExample)
CN (2) CN105452250B (enExample)
AU (2) AU2014307872B2 (enExample)
BR (2) BR122020002802B1 (enExample)
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DK (2) DK3033344T3 (enExample)
EA (3) EA202091271A3 (enExample)
ES (2) ES2654474T3 (enExample)
HK (1) HK1256262A1 (enExample)
HR (2) HRP20171895T1 (enExample)
HU (2) HUE054504T2 (enExample)
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NZ (2) NZ745811A (enExample)
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RS (2) RS56910B1 (enExample)
SG (2) SG10201801179VA (enExample)
SI (2) SI3033344T1 (enExample)
WO (1) WO2015022407A1 (enExample)
ZA (1) ZA201509204B (enExample)

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Publication number Priority date Publication date Assignee Title
JP2019131579A (ja) * 2013-08-14 2019-08-08 メルク・アンド・コンパニー ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩

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US10059710B2 (en) * 2016-02-17 2018-08-28 Merck & Cie Stable formulations of 5,10-methylene-(6R)-tetrahydrofolic acid
EP3446703A1 (en) * 2017-08-24 2019-02-27 Isofol Medical AB 6r]-mthf multiple bolus administration in 5-fluorouracil based chemotherapy
EP3446704A1 (en) * 2017-08-24 2019-02-27 Isofol Medical AB [6r]-mthf - an efficient folate alternative in 5-fluorouracil based chemotherapy
KR102753593B1 (ko) * 2017-08-16 2025-01-10 메르크 파텐트 게엠베하 5,10-메틸렌-(6r)-테트라하이드로폴산 및 디카르복시산을 포함하는 안정한 동결건조물
MX2020007009A (es) * 2018-01-05 2020-11-11 Isofol Medical Ab Metodos para tratar canceres colorrectales metastasicos y colorrectales.
CN115335740A (zh) * 2020-03-30 2022-11-11 住友化学株式会社 层叠体
CN119365186A (zh) 2022-06-08 2025-01-24 默克专利股份有限公司 包含5,10-亚甲基-(6r)-四氢叶酸二钠的组合物
CA3258607A1 (en) 2022-06-08 2023-12-14 Merck Patent Gmbh STABLE PHARMACEUTICAL COMPOSITIONS COMPRISING 5,10-METHYLENE-(6R)-TETRAHYDROFOLIC ACID AND NACL
CN119325374A (zh) 2022-06-08 2025-01-17 默克专利股份有限公司 包含5,10-亚甲基-(6r)-四氢叶酸的稳定的冻干物
US20250319022A1 (en) 2022-06-08 2025-10-16 Merck Patent Gmbh Concentrated solutions comprising sodium 5,10-methylene-(6r)-tetrahydrofolate
CN119325373A (zh) 2022-06-08 2025-01-17 默克专利股份有限公司 包含5,10-亚甲基-(6r)-四氢叶酸的浓缩溶液

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KR20080074201A (ko) 2005-12-02 2008-08-12 어드벤트륵스 파마슈티칼스, 인크. 5,10 메틸렌테트라히드로폴레이트의 안정한 약학 조성물
HRP20160950T1 (hr) 2006-12-21 2016-10-07 F. Hoffmann-La Roche Ag Polimorfi antagonista mglur5 receptora
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JP6069336B2 (ja) * 2011-10-19 2017-02-01 マーケイター メドシステムズ， インコーポレイテッド 腎の脱神経を包含する治療効果を増強するための組織および細胞の局所的調節
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Publication number Priority date Publication date Assignee Title
JP2019131579A (ja) * 2013-08-14 2019-08-08 メルク・アンド・コンパニー ５，１０−メチレン−（６ｒ）−テトラヒドロ葉酸のヘミ硫酸塩

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IL269170B (en) 2020-09-30
SI3287460T1 (sl) 2021-08-31
AU2018278943B2 (en) 2019-12-05
PL3033344T3 (pl) 2018-02-28
JP2022024035A (ja) 2022-02-08
JP2016528242A (ja) 2016-09-15
HUE054504T2 (hu) 2021-09-28
MX2016001834A (es) 2016-04-15
HRP20210743T1 (hr) 2021-06-25
BR122020002802B1 (pt) 2022-11-29
CN105452250B (zh) 2018-02-27
EA201600172A1 (ru) 2016-07-29
NZ717825A (en) 2019-11-29
EP3033344B1 (en) 2017-09-27
EA202091271A2 (ru) 2020-09-30
JP7710356B2 (ja) 2025-07-18
SI3033344T1 (en) 2018-01-31
AU2014307872A1 (en) 2016-03-24
RS56910B1 (sr) 2018-05-31
US20190106431A1 (en) 2019-04-11
US20220024940A1 (en) 2022-01-27
CY1119694T1 (el) 2018-04-04
KR20210038995A (ko) 2021-04-08
JP6764501B2 (ja) 2020-09-30
BR112016002770B1 (pt) 2022-12-06
ES2654474T3 (es) 2018-02-13
ZA201509204B (en) 2017-04-26
BR112016002770A2 (pt) 2017-08-01
AU2014307872B2 (en) 2018-09-27
CN108096200A (zh) 2018-06-01
HK1217018A1 (zh) 2016-12-16
NO3033344T3 (enExample) 2018-02-24
DK3287460T3 (da) 2021-05-03
KR102410373B1 (ko) 2022-06-22
KR102439605B1 (ko) 2022-09-05
MX382578B (es) 2025-03-13
SG11201601016PA (en) 2016-03-30
IL269170A (en) 2019-11-28
JP2018203763A (ja) 2018-12-27
NZ745811A (en) 2020-05-29
SG10201801179VA (en) 2018-03-28
HRP20171895T1 (hr) 2018-01-26
EP2837631A1 (en) 2015-02-18
HK1256262A1 (zh) 2019-09-20
CN105452250A (zh) 2016-03-30
IL244069B (en) 2019-09-26
KR20160043054A (ko) 2016-04-20
WO2015022407A1 (en) 2015-02-19
US12122783B2 (en) 2024-10-22
CA2921178C (en) 2020-12-08
JP7396960B2 (ja) 2023-12-12
EP3033344A1 (en) 2016-06-22
HUE037615T2 (hu) 2018-09-28
IL244069A0 (en) 2016-04-21
LT3287460T (lt) 2021-07-26
LT3033344T (lt) 2017-12-27
PT3287460T (pt) 2021-05-27
DK3033344T3 (en) 2017-12-18
CY1124076T1 (el) 2022-05-27
ES2871483T3 (es) 2021-10-29
JP6735321B2 (ja) 2020-08-05
US20240400574A1 (en) 2024-12-05
MX360355B (es) 2018-10-30
JP2020128410A (ja) 2020-08-27
RS61986B1 (sr) 2021-07-30
EA201892729A1 (ru) 2019-04-30
US20160185787A1 (en) 2016-06-30
EP3287460B1 (en) 2021-02-24
EA202091271A3 (ru) 2020-11-30
CA2921178A1 (en) 2015-02-19
EP3287460A1 (en) 2018-02-28
AU2018278943A1 (en) 2019-01-17
EA032179B1 (ru) 2019-04-30
JP2019131579A (ja) 2019-08-08
PT3033344T (pt) 2018-01-03
PL3287460T3 (pl) 2021-07-19

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