Hydrated and anhydrous polymorphs of 2'-O-fucosyllactose and their production methods

Patent metadata

Field	Value
Publication number	US-10988499-B2
Application number	US-201916411721-A
Country	US
Kind code	B2
Filing date	May 14, 2019
Priority date	Jul 12, 2012
Publication date	Apr 27, 2021
Grant date	Apr 27, 2021

Abstract

This invention describes new hydrated and anhydrous polymorphs of 2′-O-fucosyllactose (2′FL): Polymorph A 2′FL-3/2H2O, Polymorph B 2TL-5/2 H2O 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.

First claim

The invention claimed is:

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%.

Assignees

• Basf Se

Inventors

• Cipolletti Giovanni
• Laudati Gessica
• Salsini Liana
• Puhl Michael

Classifications

• C07H3/06 Primary

  Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• A23V2002/00

  Food compositions, function of food ingredients or processes for food or foodstuffs · CPC title

• A23L33/125

  containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates (indigestible substances A23L33/21) · CPC title

• C07H1/06

  Separation; Purification · CPC title