Tartrate salt of isofagomine and methods of use
View Patent ↗A novel tartaric acid salt of Isofagomine (Isofagomine tartrate) that can be used for the treatment of Gaucher disease is provided. The invention also provides a crystalline form of isofagomine tartrate, method for preparing the salt, a pharmaceutical composition containing the salt, and a method of treating Gaucher disease.
1. A method for the preparation of isofagomine tartrate comprising:
(a) reacting isofagomine free base or its ionized form and L-(+)-tartaric acid in a molar ratio of 1:1 in a solvent; and
(b) isolating isofagomine tartrate.
2. The method of claim 1 , wherein at least one kilogram of isofagomine tartrate is isolated.
3. The method of claim 1 , wherein the solvent is an aqueous alcohol.
4. The method of claim 1 , wherein the solvent is an alcohol selected from methanol, ethanol, propanols, butanols, or mixtures thereof.
5. The method of claim 1 , wherein the solvent is ethanol.
6. The method of claim 1 , wherein step (b) includes crystallization of isofagomine tartrate.
7. The method of claim 6 , wherein 90% or more of isofagomine tartrate has a particle size of 1200 μm or less following crystallization of isofagomine tartrate.
8. The method of claim 6 , wherein crystallization of isofagomine tartrate comprises water and a secondary solvent.
9. The method of claim 8 , wherein the secondary solvent is a protic solvent.
10. The method of claim 9 , wherein the protic solvent is an alcohol.
11. A method for preparing high purity isofagomine tartrate on an industrial scale, the method comprising,
(a) reacting about 1 kg or more isofagomine free base or its ionized form and L-(+)-tartaric acid in a molar ratio of 1:1 in a solvent;
(b) obtaining a crude isofagomine tartrate;
(c) crystallizing the crude isofagomine tartrate using an aqueous solution; and
(d) isolating high purity isofagomine tartrate.
12. The method of claim 11 wherein the aqueous solution is water.
13. The method of claim 11 , wherein the aqueous solution is a mixture of water and an alcohol wherein water and the alcohol are used at the same time or with an interval of time.
14. The method of claim 11 , wherein high purity isofagomine tartrate is at least 84% pure by weight.
15. The method of claim 11 , wherein high purity isofagomine tartrate is at least 98% pure by weight.
16. The method of claim 11 , wherein high purity isofagomine tartrate is at least 99% pure by weight.
17. The method of claim 11 , wherein 90% or more of high purity isofagomine tartrate has a particle size of 1200 μm or less.
18. A method for the preparation of isofagomine tartrate comprising:
(a) reacting isofagomine free base or its ionized form and L-(+)-tartaric acid in a molar ratio of 2:1 to 1:1 in a solvent; and
(b) isolating isofagomine tartrate.
19. The method of claim 18 , wherein at least one kilogram of isofagomine tartrate is isolated.
20. The method of claim 18 , wherein the solvent is an aqueous alcohol.
21. The method of claim 18 , wherein the solvent is an alcohol selected from methanol, ethanol, propanols, butanols, or mixtures thereof.
22. The method of claim 18 , wherein the solvent is ethanol.
23. The method of claim 18 , wherein step (b) includes crystallization of isofagomine tartrate.
24. The method of claim 23 , wherein 90% or more of isofagomine tartrate has a particle size of 1200 μm or less following crystallization of isofagomine tartrate.
25. The method of claim 23 , wherein crystallization of isofagomine tartrate comprises water and a secondary solvent.
26. The method of claim 25 , wherein the secondary solvent is a protic solvent.
27. The method of claim 26 , wherein the protic solvent is an alcohol.
28. A method for preparing high purity isofagomine tartrate on an industrial scale, the method comprising,
(a) reacting about 1 kg or more isofagomine free base or its ionized form and L-(+)-tartaric acid in a molar ratio of 2:1 to 1:1 in a solvent;
(b) obtaining a crude isofagomine tartrate;
(c) crystallizing the crude isofagomine tartrate using an aqueous solution; and
(d) isolating high purity isofagomine tartrate.
29. The method of claim 28 wherein the aqueous solution is water.
30. The method of claim 28 , wherein the aqueous solution is a mixture of water and an alcohol wherein water and the alcohol are used at the same time or with an interval of time.
31. The method of claim 28 , wherein high purity isofagomine tartrate is at least 84% pure by weight.
32. The method of claim 28 , wherein high purity isofagomine tartrate is at least 98% pure by weight.
33. The method of claim 28 , wherein high purity isofagomine tartrate is at least 99% pure by weight.
34. The method of claim 28 , wherein 90% or more of high purity isofagomine tartrate has a particle size of 1200 μm or less.