IP Library › Granted Patent US 12,234,237
Granted Patent B2
US 12,234,237 · App. 18/243,991 · Granted Feb 25, 2025

Folate salts

Inventors: Martin Ulmann (Dachsen, CH); Gerd Wiesler (Lohn, CH); Arthur Bodenmüller (Seltisberg, CH); Markus Müller
Assignee: APROFOL AG
C07D475/04A23L33/10A61K31/519C07B2200/13
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Quick Facts
Patent No.
US 12,234,237
App. No.
18/243,991
Granted
Feb 25, 2025
Kind
B2
Abstract

The invention relates to crystalline folate salts. The salt consists of a folate anion and an organic cation. The folate anion is 5-methyl-(6S)-tetrahydrofolic acid, and the cation is an organic compound which is an alkanolamine selected from the group consisting of choline, N-methylaminoethanol, 2-amino-2-methylpropanol and 2-dimethylaminoethanol.

Claims (11)

1. A crystalline folate salt comprising a tetrahydrofolic acid anion and an organic cation where the anion is 5-methyl-(6S)-tetrahydrofolic acid, and the cation is an organic compound wherein the organic compound is an alkanolamine selected from the group consisting of 2-dimethylaminoethanol, N-methylaminoethanol, and 2-amino-2methylpropanol.

2. The crystalline folate salt according to claim 1 , wherein the folate salts have a solubility of higher than 2 weight-% (w/w) based on a total weight of a solution at 20° C. in organic solvents.

3. The crystalline folate salt according to claim 1 , wherein the organic compound is mono-2-dimethylaminoethanol.

4. The crystalline folate salt according to claim 1 , wherein the organic compound is di 2-dimethylaminoethanol.

5. The crystalline folate salt according to claim 1 , wherein the organic compound is di-N-methylaminoethanol.

6. The crystalline folate salt according to claim 1 , wherein the organic compound is di-2-amino-2-methylpropanol.

7. The crystalline folate salt according to claim 1 , wherein the tetrahydrofolic acid anion is 5-methyl-(6S)-tetrahydrofolic acid and the organic cation is 2-methylaminoethanol.

8. A pharmaceutical composition, comprising at least one folate salt according to claim 1 , as a main active compound and at least a pharmaceutically acceptable excipient.

9. A method of preparing the crystalline folate salt according to claim 1 , comprising crystallizing a folate salt comprising a tetrahydrofolic acid anion and an organic cation from an organic solvent comprising water in a range of 0.2 weight-% to 12 weight-% based on a weight of the organic solvent comprising the water.

10. A method of treating deficiencies or disorders that are positively affected by the administration of a tetrahydrofolic acid salt, comprising administering the crystalline folate salt according to claim 1 to a patient in need thereof.

11. A method of preventing deficiencies or disorders that are positively affected by the administration of a tetrahydrofolic acid salt, comprising administering the crystalline folate salt according to claim 1 to a patient in need thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 8, 2024
From: ULMANN, MARTIN; WIESLER, GERD; MÜLLER (DECEASED), MARKUS; BODENMÜLLER, ARTHUR
To: APROFOL AG
Reel/Frame 066049/0001 →
Priority Claims (1)
EP 18203849 · Oct 31, 2018 · regional
Continuity (2)
Continuation 17289609
Related Publication 20230416253A1 · Dec 28, 2023
References Cited (33)
US 5382581A · Marazza et al. · 1995 [cited by applicant]
US 5710271A · Felder et al. · 1998 [cited by applicant]
US 5817659A · Muller et al. · 1998 [cited by applicant]
US 6441168B1 · Muller et al. · 2002 [cited by applicant]
US 9301922B1 · Ulmann · 2016 [cited by applicant]
US 9642853B2 · Ulmann · 2017 [cited by applicant]
US 10370350B2 · O'Neill et al. · 2019 [cited by applicant]
US 11549421B2 · Brück · 2023 [cited by applicant]
US 20110171134A1 · Iskandar et al. · 2011 [cited by applicant]
US 20160207925A1 · Fracchia · 2016 [cited by applicant]
US 20200030453A1 · Liu et al. · 2020 [cited by applicant]
CN 1277197A · 2004 [cited by applicant]
CN 102775407A · 2015 [cited by applicant]
CN 107304212A · 2017 [cited by applicant]
CN 111448196A · 2020 [cited by applicant]
EP 0626965A1 · 1994 [cited by applicant]
EP 3461826A1 · 2019 [cited by applicant]
JP H07025876A · 1995 [cited by applicant]
JP 3162073B2 · 2001 [cited by applicant]
JP 2011512366A · 2011 [cited by applicant]
JP 2016532714A · 2016 [cited by applicant]
JP 2020518655A · 2020 [cited by applicant]
JP 2021510406A · 2021 [cited by applicant]
WO 9317022A1 · 1993 [cited by applicant]
WO 2009103333A1 · 2009 [cited by applicant]
WO 2009103334A1 · 2009 [cited by applicant]
WO 2018178142A1 · 2018 [cited by applicant]
Gupta et al., “Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations”, Molecules, (Jul. 2018), vol. 23, No. 7, p. 1719, (15 pages). [cited by applicant]
Bastin et al., “Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities”. Organic Process Research & Development, (Jul. 19, 2000), vol. 4, No. 5, pp. 427-435. [cited by applicant]
Hirayama, “Crystallization Methods for Pharmaceuticals”. Handbook for creation of crystals of organic compounds, (2008), pp. 17-23, 37-40, 45-51, 57-65. [cited by applicant]
Aldrich, Aldrich Catalogue, 1998-1999, pp. 89, 417 and 1082, 4 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/EP2019/079941, dated Mar. 18, 2020, 16 pages. 2021. [cited by applicant]
Entire patent prosecution history of U.S. Appl. No. 17/289,609, filed Apr. 28, 2021, entitled, “Folate Salts”. [cited by applicant]