Method for obtaining crystalline 2′-fucosyllactose

Patent metadata

Field	Value
Publication number	US-11685759-B2
Application number	US-201917286474-A
Country	US
Kind code	B2
Filing date	Oct 17, 2019
Priority date	Oct 18, 2018
Publication date	Jun 27, 2023
Grant date	Jun 27, 2023

Abstract

The present invention relates to a method for obtaining crystalline 2′-fucosyllactose from a 2′-FL raw material, which contains 2′-FL as a main constituent and at least 0.5% by weight, frequently at least 1% by weight, in particular at least 2% by weight, more particularly at least 5% by weight, and especially at least 8% by weight,based on the total amount of mono-and oligosaccharides in the raw material, of one or more mono- or oligosaccharides different from 2′-FL, where the method comprises a)providing a solution of the 2′-FL raw material in water, which does not contain more than 10% by weight, preferably not more than 7% by weight, more preferably not more than 5% by weight of organic solvents, based on the total amount of water; b) effecting the crystallization of 2′-FL from the solution provided in step a) by inducing conditions of a controlled super saturation in the solution; and c) separating crystalline 2′-FL from the mother liquor, and where during controlled supersaturation in step b) not more than 10% by weight, preferably not more than 7% by weight, more preferably not more than 5% by weight of organic solvents are present, based on the total amount of water present during step b).

First claim

We claim:

1. Method for selectively obtaining crystalline form A or form B of 2′-fucosyllactose from a 2′-fucosyllactose raw material, which contains 2′-FL as a main constituent and at least 0.5% by weight, based on the total amount of mono-and oligosaccharides in the raw material, of one or more mono-or oligosaccharides different from 2′-fucosyllactose, where the method comprises
a) providing a solution of the 2′-fucosyllactose raw material in water, which does not contain more than 10% by weight of organic solvents, based on the total amount of water;
b) effecting the crystallization of 2′-fucosyllactose at a temperature in the range from 0 to 52° C. by inducing conditions of a controlled supersaturation in the solution, where form A or form B of 2′-fucosyllactose is obtained and a water miscible organic solvent is added to the suspension when the crystallization is almost complete; and
c) separating crystalline form A or form B of 2′-fucosyllactose from the mother liquor;
and where during controlled supersaturation in step b) not more than 10% by weight of organic solvents are present, based on the total amount of water present during step b).

2. The method of claim 1 , where the conditions of a controlled supersaturation are induced in a manner such that the ratio c:c* of the concentration c of dissolved 2′-fucosyllactose to the equilibrium solubility c* of 2′-fucosyllactose under the conditions of controlled supersaturation is from more than 1:1 to 1.5:1, thereby effecting the crystallization of 2′-fucosyllactose.

3. The method of claim 1 , where the controlled supersaturation is induced by removing water and/or by cooling.

4. The method of claim 1 , where the crystallization is effected in the presence of solid 2′-fucosyllactose and is carried out as an evaporation crystallization.

5. The method of claim 1 , where the concentration of dissolved 2′-fucosyllactose under the conditions of controlled supersaturation is in the range from 400 to 750 g/L.

6. The method of claim 1 , where the 2′-fucosyllactose raw material contains at least one oligosaccharide selected from lactose, difucosyllactose, lactulose and fucosylated lactulose.

7. The method of claim 1 , where the solution of 2′-fucosyllactose provided in step a) does not contain more than 5000 ppm of solid insoluble material, based on the total weight of the solution.

8. The method of claim 1 , where the aqueous solution of 2′-fucosyllactose provided in step a) is obtained by a fermentation process.

9. The method of claim 1 , where the aqueous solution of 2′-fucosyllactose provided in step a) is fed to a continuously operated crystallization apparatus, which contains an aqueous suspension of 2′-fucosyllactose crystals.

10. The method of claim 9 , where step b) comprises
b1) continuously feeding the aqueous solution of 2′-fucosyllactose to a crystallization apparatus containing an aqueous suspension of 2′-fucosyllactose;
b2) continuously removing water from the aqueous suspension of 2′-fucosyllactose contained in the crystallization apparatus to maintain conditions of controlled supersaturation;
b3) continuously removing the aqueous suspension of 2′-fucosyllactose from the crystallization apparatus.

11. The method of claim 9 , where a portion of the aqueous suspension of 2′-fucosyllactose removed in step b3) is mixed with the aqueous solution of 2′-fucosyllactose of step b1) and the mixture is fed back it into the crystallization apparatus.

12. The method of claim 1 , where the solution of the 2′-fucosyllactose raw material is subjected to a crystallization in batch- or fed-batch operated crystallization apparatus.

13. The method of claim 1 , where the crystallization is carried out at a temperature in the range from 20 to 52° C. in the presence of solid 2′-fucosyllactose and where the crystallization is effected from an aqueous supersaturated solution under the conditions of controlled supersaturation, where the aqueous supersaturated solution has a concentration of dissolved 2′-fucosyllactose in the range from 410 to 630 g/L.

14. The method of claim 1 , where at least a portion of the mother liquor obtained in step c) is subjected to a crystallization of 2′-fucosyllactose by inducing conditions of a controlled supersaturation in the mother liquor.

15. The method of claim 14 , where at least a portion of the mother liquor is mixed with the solution of the 2′-fucosyllactose raw material prior to carrying out step b).

16. The method of claim 1 , which comprises a first crystallization step and a second crystallization step,
where the aqueous solution of the 2′-fucosyllactose raw material provided in step a) is subjected to a crystallization of the second crystallization step,
where in the second crystallization step the crystallization of 2′-fucosyllactose is effected by inducing conditions of a controlled supersaturation in the solution according to step b), where the aqueous suspension of the crystalline 2′-fucosyllactose obtained in the second crystallization step is subjected to a solid-liquid separation to obtain a crystalline 2′-fucosyllactose and a mother liquor,
where the mother liquor obtained in the solid-liquid separation is introduced into the first crystallization step.

17. The method of claim 16 , where the crystalline 2′-fucosyllactose obtained in the first crystallization step is dissolved in the aqueous solution of the 2′-fucosyllactose raw material prior to carrying out the second crystallization step.

Assignees

• Basf Se

Inventors

• Puhl Michael
• Wloch Sebastian
• Oedman Peter
• Letzel Anne-Catrin
• Schroeder Hartwig
• Malisz Jacek
• Seibert-Ludwig Daniel
• Kappert Emiel Jan
• Wong Chung Huan
• Barros Gross Michael
• Viertelhaus Martin

Classifications

• C07H1/08 Primary

  from natural products · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07H3/06 Primary

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

• C07H1/06

  Separation; Purification · CPC title

• C12P19/04

  Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds · CPC title