JP7232815B2 - ５，１０－メチレン－（６ｒ）－テトラヒドロ葉酸を含む安定な凍結乾燥物 - Google Patents

５，１０－メチレン－（６ｒ）－テトラヒドロ葉酸を含む安定な凍結乾燥物 Download PDF

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JP7232815B2
JP7232815B2 JP2020508004A JP2020508004A JP7232815B2 JP 7232815 B2 JP7232815 B2 JP 7232815B2 JP 2020508004 A JP2020508004 A JP 2020508004A JP 2020508004 A JP2020508004 A JP 2020508004A JP 7232815 B2 JP7232815 B2 JP 7232815B2
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acid
methylene
pharmaceutically acceptable
thf
tetrahydrofolic acid
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JP2020531415A5 (enExample
JP2020531415A (ja
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ルドルフ モーザー、
ヴィオーラ グレーン、
トーマス アムマン、
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Merck Patent GmbH
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Merck Patent GmbH
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    • 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
    • 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
    • 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
    • A61K9/08—Solutions
    • 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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
    • C07C55/02—Dicarboxylic acids
    • C07C55/06—Oxalic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C55/00—Saturated compounds having more than one carboxyl group bound to acyclic carbon atoms
    • C07C55/02—Dicarboxylic acids
    • C07C55/10—Succinic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/13—Dicarboxylic acids
    • C07C57/145—Maleic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/13—Dicarboxylic acids
    • C07C57/15—Fumaric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C07C59/255—Tartaric acid

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Dispersion Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
JP2020508004A 2017-08-16 2018-08-15 ５，１０－メチレン－（６ｒ）－テトラヒドロ葉酸を含む安定な凍結乾燥物 Active JP7232815B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP17186518 2017-08-16
EP17186518.1 2017-08-16
PCT/EP2018/072077 WO2019034673A1 (en) 2017-08-16 2018-08-15 STABLE LYOPHILISATES COMPRISING 5,10-METHYLENE- (6R) -TETRAHYDROFOLIC ACID AND DICARBOXYLIC ACID

Publications (3)

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JP2020531415A JP2020531415A (ja) 2020-11-05
JP2020531415A5 JP2020531415A5 (enExample) 2021-09-24
JP7232815B2 true JP7232815B2 (ja) 2023-03-03

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JP2020508004A Active JP7232815B2 (ja) 2017-08-16 2018-08-15 ５，１０－メチレン－（６ｒ）－テトラヒドロ葉酸を含む安定な凍結乾燥物

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US (1) US11337978B2 (enExample)
EP (1) EP3668516B1 (enExample)
JP (1) JP7232815B2 (enExample)
KR (1) KR102753593B1 (enExample)
CN (1) CN110996958B (enExample)
AU (1) AU2018317789B2 (enExample)
CA (1) CA3073127A1 (enExample)
DK (1) DK3668516T3 (enExample)
ES (1) ES2902051T3 (enExample)
PT (1) PT3668516T (enExample)
WO (1) WO2019034673A1 (enExample)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4536184A1 (en) 2022-06-08 2025-04-16 Merck Patent GmbH Concentrated solutions comprising sodium 5,10-methylene-(6r)- tetrahydrofolate
WO2023237484A1 (en) * 2022-06-08 2023-12-14 Merck Patent Gmbh Compositions comprising disodium 5,10-methylene-(6r)-tetrahydrofolate
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
EP4536186A1 (en) * 2022-06-08 2025-04-16 Merck Patent GmbH Concentrated solutions comprising 5,10-methylene-(6r)-tetrahydrofolic acid

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005524655A (ja) 2002-02-26 2005-08-18 メルック・エプロバ・アクチエンゲゼルシヤフト 炎症及び炎症に関連する疾患の予防及び治療に適する、特に炎症マーカーｃｒｐ及びｓａａに影響を与えるのに適する調合物の製造にホラートを使用する方法
JP2009514776A (ja) 2003-06-26 2009-04-09 メルック・エプロバ・アクチエンゲゼルシヤフト ５，１０−メチレンテトラヒドロホラートの安定な医薬調合物
JP2009518305A (ja) 2005-12-02 2009-05-07 アドベントアールエックス ファーマシューティカルズ， インコーポレイテッド ５，１０メチレンテトラヒドロ葉酸の安定な薬学的組成物
JP2013227274A (ja) 2012-03-28 2013-11-07 Kose Corp 葉酸含有組成物及び葉酸の安定化方法
US20160074402A1 (en) 2013-04-30 2016-03-17 Aprofol Ag Stable pharmaceutical composition containing folates
JP2016528242A (ja) 2013-08-14 2016-09-15 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

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0165926B1 (en) 1983-05-20 1990-10-24 Bengt Gustavsson A device for transferring a substance
US5747469A (en) 1991-03-06 1998-05-05 Board Of Regents, The University Of Texas System Methods and compositions comprising DNA damaging agents and p53
CH682664A5 (en) 1991-10-15 1993-10-29 Eprova Ag Stable salts of 5,10-methylene tetrahydrofolate.
CH684644A5 (de) 1992-07-13 1994-11-15 Eprova Ag 5,10-Methylentetrahydrofolsäure-Cyclodextrin-Einschlussverbindungen.
US20020103126A1 (en) 1997-04-18 2002-08-01 Roche Diagnostics Gmbh Stable pharmaceutical form of administration for peptides, proteins and nucleic acids
GB9904387D0 (en) 1999-02-25 1999-04-21 Pharmacia & Upjohn Spa Antitumour synergistic composition
AU2012234323A1 (en) 2011-03-29 2013-10-17 Sanofi Otamixaban formulations with improved stability
CN107812195B (zh) 2014-09-04 2021-04-20 连云港金康和信药业有限公司 (6s)‐5‐甲基‐四氢叶酸钙盐的稳定药物组合物
US10059710B2 (en) * 2016-02-17 2018-08-28 Merck & Cie Stable formulations of 5,10-methylene-(6R)-tetrahydrofolic acid

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005524655A (ja) 2002-02-26 2005-08-18 メルック・エプロバ・アクチエンゲゼルシヤフト 炎症及び炎症に関連する疾患の予防及び治療に適する、特に炎症マーカーｃｒｐ及びｓａａに影響を与えるのに適する調合物の製造にホラートを使用する方法
JP2009514776A (ja) 2003-06-26 2009-04-09 メルック・エプロバ・アクチエンゲゼルシヤフト ５，１０−メチレンテトラヒドロホラートの安定な医薬調合物
JP2009518305A (ja) 2005-12-02 2009-05-07 アドベントアールエックス ファーマシューティカルズ， インコーポレイテッド ５，１０メチレンテトラヒドロ葉酸の安定な薬学的組成物
JP2013227274A (ja) 2012-03-28 2013-11-07 Kose Corp 葉酸含有組成物及び葉酸の安定化方法
US20160074402A1 (en) 2013-04-30 2016-03-17 Aprofol Ag Stable pharmaceutical composition containing folates
JP2016528242A (ja) 2013-08-14 2016-09-15 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

Also Published As

Publication number Publication date
US11337978B2 (en) 2022-05-24
ES2902051T3 (es) 2022-03-24
AU2018317789B2 (en) 2023-06-29
EP3668516A1 (en) 2020-06-24
US20200368236A1 (en) 2020-11-26
AU2018317789A1 (en) 2020-04-02
CA3073127A1 (en) 2019-02-21
WO2019034673A1 (en) 2019-02-21
RU2020110073A3 (enExample) 2022-01-24
CN110996958B (zh) 2023-05-12
EP3668516B1 (en) 2021-09-22
RU2020110073A (ru) 2021-09-16
PT3668516T (pt) 2021-12-23
JP2020531415A (ja) 2020-11-05
DK3668516T3 (da) 2021-12-13
KR102753593B1 (ko) 2025-01-10
KR20200041354A (ko) 2020-04-21
CN110996958A (zh) 2020-04-10

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