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IE780285L - PROCESS FOR THE PREPARATION OF d,l -5-METHYLTETRAHYDROFOLIC¹ACID - Google Patents

PROCESS FOR THE PREPARATION OF d,l -5-METHYLTETRAHYDROFOLIC¹ACID

Info

Publication number
IE780285L
IE780285L IE780285A IE28578A IE780285L IE 780285 L IE780285 L IE 780285L IE 780285 A IE780285 A IE 780285A IE 28578 A IE28578 A IE 28578A IE 780285 L IE780285 L IE 780285L
Authority
IE
Ireland
Prior art keywords
preparation
formula
acid
folic acid
action
Prior art date
Application number
IE780285A
Other versions
IE46402B1 (en
Original Assignee
Bioresearch Sas
Camozzi Livio Dr And C
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bioresearch Sas, Camozzi Livio Dr And C filed Critical Bioresearch Sas
Publication of IE780285L publication Critical patent/IE780285L/en
Publication of IE46402B1 publication Critical patent/IE46402B1/en

Links

Classifications

    • 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
    • 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
    • A61K47/20Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • 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
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2013Organic compounds, e.g. phospholipids, fats
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Process for the preparation of d,l-5-methyltetrahydrofolic acid and its salts of the formula 1 in which X is hydrogen, an alkali metal or the equivalent of an alkaline earth metal, by reduction of folic acid with NaBH4 and methylation of the tetrahydrofolic acid obtained with aqueous solutions of formaldehyde and sodium borohydride in an inert gas atmosphere. The process is simple and can be carried out without separation of intermediates while carrying out the process steps successively in the same reaction vessel. The final products are obtained in a yield of more than 80%, relative to folic acid employed, in a purity of more than 99%. The compounds of the formula I obtained are non-toxic, stable at physiological pH and suitable for the preparation of liquid or solid pharmaceutical compositions for any type of application in human therapy. Such compositions exhibit haematopoietic action, hepatoprotective and antineoplastic action. <IMAGE> [GB1572137A]
IE285/78A 1977-02-22 1978-02-09 Process for the preparation of d, 1-5-methyltetra-hydrofolic acid IE46402B1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB7290/77A GB1572137A (en) 1977-02-22 1977-02-22 Stable compositions for therapeutic use based on d,1-5-methyltetrahydrofolic acid and its salts

Publications (2)

Publication Number Publication Date
IE780285L true IE780285L (en) 1978-08-22
IE46402B1 IE46402B1 (en) 1983-06-01

Family

ID=9830275

Family Applications (1)

Application Number Title Priority Date Filing Date
IE285/78A IE46402B1 (en) 1977-02-22 1978-02-09 Process for the preparation of d, 1-5-methyltetra-hydrofolic acid

Country Status (32)

Country Link
JP (1) JPS5831353B2 (en)
AR (1) AR215162A1 (en)
AT (1) AT380020B (en)
AU (1) AU520715B2 (en)
BE (1) BE863808A (en)
CA (1) CA1093554A (en)
CH (1) CH635344A5 (en)
CZ (1) CZ279815B6 (en)
DD (1) DD134099A5 (en)
DE (1) DE2807393A1 (en)
DK (1) DK144944C (en)
EG (1) EG13399A (en)
ES (1) ES467153A1 (en)
FI (1) FI67082C (en)
FR (2) FR2381047A1 (en)
GB (1) GB1572137A (en)
GR (1) GR71704B (en)
HU (1) HU179422B (en)
IE (1) IE46402B1 (en)
IL (1) IL54052A (en)
IN (1) IN149574B (en)
LU (1) LU79067A1 (en)
MX (1) MX5288E (en)
NL (1) NL190285C (en)
NO (1) NO147793C (en)
NZ (1) NZ186465A (en)
PL (1) PL118654B1 (en)
PT (1) PT67656B (en)
SE (1) SE437028B (en)
SU (1) SU747427A3 (en)
YU (1) YU40505B (en)
ZA (1) ZA78837B (en)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5838285A (en) * 1981-08-25 1983-03-05 Kanegafuchi Chem Ind Co Ltd Preparation of 5-methyl-(6rs)-5,6,7,8-tetrahydro-l-folic acid magnesium salt or its free acid
GB8621268D0 (en) * 1986-09-03 1986-10-08 Univ Strathclyde Separation of substances
IT1229517B (en) * 1989-01-31 1991-09-03 Bioresearch Spa USE OF 5-METHYLTETRAHYDROPHOLIC ACID, OF 5 FORMYLTHETRAHYDROPHOLIC ACID, AND OF THEIR PHARMACEUTICALLY ACCEPTABLE SALTS FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS IN THE FORM OF CONTROLLED RELEASE SUITABLE FOR BEING EMPLOYED IN THE TREATMENT OF DISORDERS IN THE TREATMENT OF DISORDERS.
IT1229203B (en) * 1989-03-22 1991-07-25 Bioresearch Spa USE OF 5 METHYLTHETRAHYDROPHOLIC ACID, 5 FORMYLTHETRAHYDROPHOLIC ACID AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS IN THE FORM OF CONTROLLED RELEASE ACTIVE IN THE THERAPY OF MENTAL AND ORGANIC DISORDERS.
NL8901432A (en) * 1989-06-06 1991-01-02 Pharmachemie Bv STABLE AQUEOUS FOLINATE SOLUTION AT REFRIGERATOR TEMPERATURE, AND METHOD FOR PREPARING THAT.
CH680731A5 (en) * 1990-04-12 1992-10-30 Sapec Fine Chemicals
US5217974A (en) * 1991-03-29 1993-06-08 Eli Lilly And Company Method for treating gar-transformylase tumors in mammals and reducing mammalian toxicity
CH683261A5 (en) * 1991-10-10 1994-02-15 Applied Pharma Res A process for the preparation of Methyltetrahydrofolic in the form (6 (R, S) (-)) N-5 and separation of the active diastereoisomer (6 (S) (-)) N-5) in the form of salts.
CH682665A5 (en) * 1991-10-29 1993-10-29 Sapec Fine Chemicals Process for the purification of crude alkaline earth metal salts from N (5) -methyl-5,6,7,8-tetrahydrofolic acid.
US6162914A (en) * 1998-04-24 2000-12-19 Cerbios-Pharma S.A. Process for the reduction of pterins
CH693905A5 (en) 1999-04-15 2004-04-15 Eprova Ag Stable crystalline salts of 5-methyl tetrahydrofolic acid.
CH698729B1 (en) * 2007-05-30 2009-10-15 Cerbios Pharma Sa Stable crystalline (6S) -N (5) -methyl-5, 6,7,8-tetrahydrofolic acid.
CN103214487A (en) * 2013-04-12 2013-07-24 张家港威胜生物医药有限公司 Synthesis of important medical chemical raw material (6S)-5-methyl tetrahydrofolate
WO2015193778A1 (en) 2014-06-16 2015-12-23 Mylan Laboratories Ltd. Crystalline form of levomefolate calcium
KR102773639B1 (en) * 2018-08-28 2025-02-25 피엠씨 올가노메탈릭스, 인코포레이티드 Low-glass 2-mercaptoethanol ester and uses thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL80276C (en) *
GB1293541A (en) * 1969-03-18 1972-10-18 John Alexander Blair Folic acid derivatives
US3856959A (en) * 1972-07-24 1974-12-24 Department Of Health Education Inhibition of leukemia utilizing 5-methyltetrahydrohomofolate
US4148999A (en) * 1977-08-22 1979-04-10 The Government Of The United States Of America Preparation and purification of citrovorum factor
CH649550A5 (en) * 1984-02-09 1985-05-31 Eprova Ag Process for the preparation of alkaline earth metal salts of 5-methyltetrahydrofolic acid

Also Published As

Publication number Publication date
CA1093554A (en) 1981-01-13
DK76578A (en) 1978-08-23
FI780565A7 (en) 1978-08-23
FI67082C (en) 1985-01-10
AU3343078A (en) 1979-08-30
MX5288E (en) 1983-06-06
PT67656A (en) 1978-03-01
GR71704B (en) 1983-06-21
PL118654B1 (en) 1981-10-31
FI67082B (en) 1984-09-28
FR2385397B1 (en) 1981-07-17
HU179422B (en) 1982-10-28
IN149574B (en) 1982-01-30
NZ186465A (en) 1980-10-08
SE7801973L (en) 1978-08-23
ES467153A1 (en) 1978-11-16
NO147793C (en) 1983-06-15
JPS53124297A (en) 1978-10-30
BE863808A (en) 1978-05-29
AT380020B (en) 1986-03-25
NO147793B (en) 1983-03-07
ZA78837B (en) 1979-09-26
PT67656B (en) 1979-07-19
IL54052A0 (en) 1978-04-30
FR2381047A1 (en) 1978-09-15
NL190285C (en) 1994-01-03
YU40505B (en) 1986-02-28
AR215162A1 (en) 1979-09-14
NO780594L (en) 1978-08-23
IE46402B1 (en) 1983-06-01
NL7801775A (en) 1978-08-24
SE437028B (en) 1985-02-04
ATA90378A (en) 1985-08-15
PL204747A1 (en) 1979-03-12
LU79067A1 (en) 1978-06-27
AU520715B2 (en) 1982-02-25
IL54052A (en) 1981-07-31
CZ279815B6 (en) 1995-07-12
GB1572137A (en) 1980-07-23
CH635344A5 (en) 1983-03-31
JPS5831353B2 (en) 1983-07-05
FR2385397A1 (en) 1978-10-27
YU37978A (en) 1983-01-21
NL190285B (en) 1993-08-02
FR2381047B1 (en) 1981-07-24
SU747427A3 (en) 1980-07-23
EG13399A (en) 1981-12-31
DK144944B (en) 1982-07-12
DE2807393A1 (en) 1978-09-07
DE2807393C2 (en) 1990-06-13
CZ112978A3 (en) 1995-02-15
DD134099A5 (en) 1979-02-07
DK144944C (en) 1982-11-29

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