Abstract: A process for preparing and concentrating (6S,?S) or (6S,?R) tetrahydrofolic acid ester salts and (6S,?S) or (6S,?R) tetrahydrofolic acid, characterized by preparing or dissolving equimolar or concentrated mixtures of diastereomers of addition salts of tetrahydrofolic acid esters with aromatic sulphonic acids in organic solvents, followed by crystallizing them at least once, and then if applicable hydrolyzing the crystallizate to produce (6S,?S) or (6S,?R) tetrahydrofolic acid, crystallizing the latter as a free acid or isolating it in the form of a salt.
Type:
Grant
Filed:
July 12, 2000
Date of Patent:
February 22, 2005
Assignee:
EPROVA AG
Inventors:
Hans Rudolf Muller, Rudolf Moser, Viola Groehn
Abstract: The invention relates to the use of at least folic acid or a folate and tetrahydrobiopterin (BH4) or derivatives thereof for treating or preventing cardiovascular or neurological disorders by modulation of the activity of nitric oxide synthase (NOS).
Abstract: Pure and extremely stable crystalline (6R)-tetrahydrofolic acids, absolutely inert even when exposed to air and elevated temperature without stabilizers being added, are prepared by a crystallization process at a pH of ≧2.
Type:
Grant
Filed:
January 8, 2001
Date of Patent:
July 22, 2003
Assignee:
Eprova AG
Inventors:
Hans Rudolf Müller, Martin Ulmann, Rudolf Moser, Thomas Ammann
Abstract: This invention relates to stable crystalline salts of 5-methyl-(6R,S)-, -(6S)- and -(6R)-tetrahydrofolic acid, to methods of producing these salts and to the use thereof use as a constituent for the production of drugs or as a food additive, and to preparations containing these salts.
Type:
Grant
Filed:
April 17, 2000
Date of Patent:
August 27, 2002
Assignee:
Eprova AG
Inventors:
Rudolf Müller, Rudolf Moser, Thomas Egger
Abstract: Pure and extremely stable crystalline (6S)- and (6R)-tetrahydrofolic acids, absolutely inert even when exposed to air and elevated temperature without stabilizers being added, are prepared by a crystallization process at a pH of ≧3.5 for the preparation of crystalline (6S)-tetrahydrofolic acid and at a pH of ≧2 for the preparation of crystalline (6R)-tetrahydrofolic acid.
Type:
Grant
Filed:
January 26, 1998
Date of Patent:
August 7, 2001
Assignee:
Eprova AG
Inventors:
Hans Rudolf Müller, Martin Ulmann, Rudolf Moser, Thomas Ammann
Abstract: This invention relates to the use of tetrahydrofolates in natural stereoisomeric form for the production of a pharmaceutical preparation suitable for influencing the homocysteine level, particularly for assisting the remethylation of homocysteine. Clinical areas of application include all anomalies of the homocysteine level, particularly the prevention and treatment of cardiovascular diseases and the prevention of neural tube deficiencies.
Type:
Grant
Filed:
June 11, 1998
Date of Patent:
January 4, 2000
Assignee:
Eprova AG
Inventors:
Hans Rudolf Muller, Martin Ulmann, Rudolf Moser
Abstract: This invention relates to stable crystalline salts of (6R,S)-, (6S)- and (6R)-tetrahydrofolic acid, to methods of preparing these salts and to their use as an ingredient for the production of drugs and pharmaceutical preparations.
Type:
Grant
Filed:
November 7, 1996
Date of Patent:
October 6, 1998
Assignee:
Eprova AG
Inventors:
Hans R. Muller, Martin Ulmann, Rudolf Moser, Thomas Ammann
Abstract: The invention relates to a process for preparing (6S)-folinic acid and its salts by recrystallization of alkaline-earth salts of (6R,S)-folinic acid and, where necessary, liberation of the acid from the alkaline-earth folinates and/or, where necessary, conversion into the alkali salts by at least one recrystallization in the presence of a base.The invention also relates to calcium-, magnesium-, potassium- and sodium-(6S)-folinates and to (6S)-folinic acid prepared in accordance with the invention.
Type:
Grant
Filed:
June 2, 1992
Date of Patent:
September 13, 1994
Assignee:
Eprova AG
Inventors:
Hans R. Mueller, Martin Ulmann, Josef Conti, Gunter Muerdel
Abstract: A method for the resolution of (6R,S)-folinates into their diastereomers, comprising adding a water-soluble alkali metal, ammonium or alkaline earth metal salt of an inorganic or organic acid to an aqueous solution of a salt of (6R,S)-folinic acid, removing by filtration the salt which separates out, which consists predominantly of the corresponding (6R)-folinates, and isolating the desired (6S)-folinate from the filtrate.
Type:
Grant
Filed:
November 7, 1989
Date of Patent:
April 23, 1991
Assignee:
Eprova AG
Inventors:
Hans R. Mueller, Martin Ulmann, Josef Conti, Guenter Muerdel
Abstract: For the preparation of 5,10-methenyl-(6R)-, 5-formyl-(6S)- or 5-methyl-(6S)-tetrahydrofolic acid or salts thereof, 5,10-methenyl-(6R,S)-tetrahydrofolic acid, the inner salt thereof or one of the salts thereof with strong acids is subjected to diastereomer separation by fractional crystallization and, if desired, the resulting 5,10-methenyl-(6R)-tetrahydrofolic acid is converted by treatment with a hydrolyzing agent into 5-formyl-(6S)-tetrahydrofolic acid or by treatment with a reducing agent into 5-methyl-(6S)-tetrahydrofolic acid, and the resulting free acid may be converted into one of its salts by treatment with a base.
Type:
Grant
Filed:
June 29, 1989
Date of Patent:
April 9, 1991
Assignee:
Eprova AG
Inventors:
Hans R. Muller, Martin Ulmann, Josef Conti, Gunter Murdel