Hydrated and anhydrous polymorphs of 2'-O-fucosyllactose and their production methods
This invention describes new hydrated and anhydrous polymorphs of 2′-O-fucosyllactose (2′FL): Polymorph A 2′FL-3/2H 2 O, Polymorph B 2TL-5/2 H 2 O and anhydrous Polymorph C. There is also a description of the methods for obtaining them, and of a new method for preparing Polymorph I already known in the literature.
1. A method for obtaining crystalline 2′-O-Fucosyllactose (2′FL)hydrate in form of polymorph A with molecular formula C 18 H 32 O 15 .nH 2 O wherein n is 3/2, the method comprising:
drying a 2′FL hydrate in form of polymorph B with molecular formula C 18 H 32 O 15 .nH 2 O wherein n is 5/2, thereby transforming the 2′FL hydrate polymorph B into polymorph A.
2. The method of claim 1 , wherein the 2′FL hydrate polymorph B is in solid form during drying.
3. The method of claim 1 , comprising drying the 2′FL hydrate polymorph B in a dry atmosphere.
4. The method of claim 1 , comprising drying the 2′FL hydrate polymorph B for 12 hr to 48 hr.
5. The method of claim 1 , comprising drying the 2′FL hydrate polymorph B at a temperature in a range of 46° C. to 65° C., followed by cooling to room temperature.
6. The method of claim 1 , wherein drying comprises heating the 2′FL hydrate polymorph B at a temperature up to 150° C.
7. The method of claim 1 , wherein drying comprises heating the 2′FL hydrate polymorph B to a temperature of 150° C., and then cooling to a temperature of 25° C.
8. The method of claim 1 , wherein drying comprises heating the 2′FL hydrate polymorph B to a temperature of 150° C. at a rate of 5° C./min, and then cooling to a temperature of 25° C. at a rate of 5° C./min.
9. The method of claim 1 , wherein the 2′FL hydrate polymorph B, before transforming into the 2′FL hydrate polymorph A, passes through an anhydrous phase.
10. The method of claim 9 , wherein the anhydrous phase has characteristic XRPD peaks at 9.96±0.20, 18.88±0.20, and 1.17±0.20 2Θ.
11. The method of claim 1 , wherein the polymorph A has characteristic XRPD peaks at 18.86±0.20, 9.89±0.20, and 17.05±0.20 2Θ.
12. The method of claim 1 , wherein the polymorph A has characteristic XRPD peaks at 18.86±0.20, 9.89±0.20, 17.05±0.20, 21.65±0.20, and 14.20±0.20 2Θ.
13. The method of claim 1 , wherein a single crystal of the polymorph A has a P2 1 2 1 2 1 spatial group which is arranged within an orthorhombic crystalline system and the crystal comprises elementary cells having the following parameters: a=12.4098(8) Å, b=12.737(2) Å, c=13.756(2) Å and a volume of 2212.5 Å 3 .
14. The method of claim 1 , wherein the polymorph A has a β anomeric conformation.
15. The method of claim 1 , wherein the polymorph A has a predominantly β anomeric conformation with an α anomer content of less than 15%.
16. The method of claim 1 , wherein the polymorph B has characteristic XRPD peaks at 9.96±0.20, 18.56±0.20, and 20.48±0.20 2Θ.
17. The method of claim 1 , wherein the polymorph B has characteristic XRPD peaks at 9.96±0.20, 18.56±0.20, 20.48±0.20, 14.21±0.20, and 11.90±0.20 2Θ.
18. The method of claim 1 , wherein a single crystal of the polymorph B has a P2 1 2 1 2 1 spatial group which is arranged within an orthorhombic crystalline system and the crystal comprises elementary cells having the following parameters: a=14.905(7) Å, b=12.663(6) Å, c=12.447(5) Å and a volume of 2349.4 Å 3 .
19. The method of claim 1 , wherein the polymorph B has a β anomeric conformation.
20. The method of claim 1 , wherein the polymorph B has a predominantly β anomeric conformation with an α anomer content of less than 10%.