CA2921178C - Hemisulfate salt of 5,10-methylene-(6r)-tetrahydrofolic acid - Google Patents

Hemisulfate salt of 5,10-methylene-(6r)-tetrahydrofolic acid Download PDF

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Publication number
CA2921178C
CA2921178C CA2921178A CA2921178A CA2921178C CA 2921178 C CA2921178 C CA 2921178C CA 2921178 A CA2921178 A CA 2921178A CA 2921178 A CA2921178 A CA 2921178A CA 2921178 C CA2921178 C CA 2921178C
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Prior art keywords
hemisulfate salt
thf
hemisulfate
water
lyophilisate
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CA2921178A
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English (en)
French (fr)
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CA2921178A1 (en
Inventor
Rudolf Moser
Viola Groehn
Thomas Egger
Thomas Ammann
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Merck et Cie
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Merck et Cie
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D475/00Heterocyclic compounds containing pteridine ring systems
    • C07D475/02Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
    • C07D475/04Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
    • 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
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K47/02Inorganic 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
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19Particulate 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D475/00Heterocyclic compounds containing pteridine ring systems
    • C07D475/12Heterocyclic compounds containing pteridine ring systems containing pteridine ring systems condensed with carbocyclic rings or ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D475/00Heterocyclic compounds containing pteridine ring systems
    • C07D475/12Heterocyclic compounds containing pteridine ring systems containing pteridine ring systems condensed with carbocyclic rings or ring systems
    • C07D475/14Benz [g] pteridines, e.g. riboflavin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12Heterocyclic 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
    • C07D487/14Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13Crystalline 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)
CA2921178A 2013-08-14 2014-08-14 Hemisulfate salt of 5,10-methylene-(6r)-tetrahydrofolic acid Active CA2921178C (en)

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

Publications (2)

Publication Number Publication Date
CA2921178A1 CA2921178A1 (en) 2015-02-19
CA2921178C true CA2921178C (en) 2020-12-08

Family

ID=48998397

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2921178A Active CA2921178C (en) 2013-08-14 2014-08-14 Hemisulfate salt of 5,10-methylene-(6r)-tetrahydrofolic acid

Country Status (27)

Country Link
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)
CA (1) CA2921178C (enExample)
CY (2) CY1119694T1 (enExample)
DK (2) DK3033344T3 (enExample)
EA (3) EA202091271A3 (enExample)
ES (2) ES2654474T3 (enExample)
HK (1) HK1256262A1 (enExample)
HR (2) HRP20171895T1 (enExample)
HU (2) HUE054504T2 (enExample)
IL (2) IL244069B (enExample)
LT (2) LT3033344T (enExample)
MX (2) MX382578B (enExample)
NO (1) NO3033344T3 (enExample)
NZ (2) NZ745811A (enExample)
PL (2) PL3033344T3 (enExample)
PT (2) PT3287460T (enExample)
RS (2) RS56910B1 (enExample)
SG (2) SG10201801179VA (enExample)
SI (2) SI3033344T1 (enExample)
WO (1) WO2015022407A1 (enExample)
ZA (1) ZA201509204B (enExample)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2837631A1 (en) * 2013-08-14 2015-02-18 Merck & Cie New stable salt of 5,10-methylene-(6R)-tetrahydrofolic acid
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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AU575814B2 (en) 1983-03-03 1988-08-11 Bengt Gustavsson A device for transferring a substance
DE3821875C1 (enExample) * 1988-06-29 1990-02-15 Eprova Ag, Forschungsinstitut, Schaffhausen, Ch
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.
HU226998B1 (en) * 2000-11-23 2010-04-28 Richter Gedeon Nyrt Desloratadine hemisulphate, process for the preparation thereof and pharmaceutical compositions containing the same
CH696628A5 (de) 2002-02-26 2007-08-31 Eprova Ag Verwendung von Folaten zur Herstellung einer Zubereitung geeignet zur Vorbeugung und Behandlung von Entzündungen und entzündungsassoziierter Krankheiten, im Speziellen zur Beeinflussung der
CH697021A5 (de) 2003-06-26 2008-03-31 Merck Eprova Ag Stabile pharmazeutische Zusammensetzungen von 5, 10-Methylentetrahydrofolat.
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
JP5294968B2 (ja) 2009-05-01 2013-09-18 三星ダイヤモンド工業株式会社 スクライブヘッド及び該スクライブヘッドを用いたスクライブ装置
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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EP2837631A1 (en) * 2013-08-14 2015-02-18 Merck & Cie New stable salt of 5,10-methylene-(6R)-tetrahydrofolic acid
JP6971761B2 (ja) * 2017-10-11 2021-11-24 株式会社Ihiプラント タンクの構築方法

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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
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
JP6617104B2 (ja) 2019-12-04
PL3287460T3 (pl) 2021-07-19

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