Production method for crystal of reduced coenzyme Q10 having excellent stability

Patent metadata

Field	Value
Publication number	US-11453633-B2
Application number	US-201917271735-A
Country	US
Kind code	B2
Filing date	Aug 29, 2019
Priority date	Aug 30, 2018
Publication date	Sep 27, 2022
Grant date	Sep 27, 2022

Abstract

Provided is a production method capable of efficiently producing a reduced coenzyme Q10 Form II crystal. The method for producing a reduced coenzyme Q10 Form II crystal includes: adding a reduced coenzyme Q10 Form II crystal as a seed crystal to a solution with a temperature of 32° C. to 43° C., the solution containing fa) at least one organic solvent selected from the group consisting of an alcohol, a hydrocarbon, an aliphatic acid ester and a nitrogen compound, and (b) reduced coenzyme Q10, to prepare a mixture, and precipitating the reduced coenzyme Q10 from the mixture, in the form of the reduced coenzyme Q10 Form II crystal.

First claim

The invention claimed is:

1. A method for producing a reduced coenzyme Q10 Form II crystal, comprising:
adding a reduced coenzyme Q10 Form II crystal as a seed crystal to a solution with a temperature of 32° C. to 43° C., said solution comprising (a) at least one organic solvent selected from the group consisting of an alcohol, a hydrocarbon, an aliphatic acid ester and a nitrogen compound, and (b) reduced coenzyme Q10, to prepare a mixture, and
precipitating the reduced coenzyme Q10 from the mixture, in the form of the reduced coenzyme Q10 Form II crystal;
wherein the reduced coenzyme Q10 Form II crystal is obtained with a Form II rate of 70-100%; or
wherein the reduced coenzyme Q10 Form II crystal is obtained with a recovery rate of 78-99%.

2. The method according to claim 1 , wherein an amount of the seed crystal added is 0.5% to 20% by weight, based on a weight of the reduced coenzyme Q10 in the solution before the addition of the seed crystal.

3. The method according to claim 1 , wherein the organic solvent comprises 0.5% to 34% by weight of water.

4. The method according to claim 1 , wherein the organic solvent is a monohydric alcohol having 1 to 5 carbon atoms.

5. The method according to claim 4 , wherein the monohydric alcohol having 1 to 5 carbon atoms is ethanol.

6. The method according to claim 5 , wherein the ethanol comprises 8% by weight or less of water or does not comprise water.

7. The method according to claim 1 , further comprising, before the preparation of the mixture,
heating a raw material mixture containing the organic solvent and the reduced coenzyme Q10 to 42° C. or higher, so that the reduced coenzyme Q10 is dissolved in the organic solvent, and
cooling the solution resulting after the heating to a temperature that is lower than the heating temperature and in the range of 32° C. to 43° C., to prepare a solution of the reduced coenzyme Q10, wherein the solution is supersaturated.

8. The method according to claim 1 , wherein the precipitating the reduced coenzyme Q10 comprises maintaining the temperature of the mixture at 32° C. or higher for 1 hour or more after the adding the seed crystal.

9. The method according to claim 1 , wherein the precipitating the reduced coenzyme Q10 comprises decreasing over time the temperature of the mixture.

10. The method according to claim 1 , wherein the precipitating the crystal comprises:
maintaining the temperature of the mixture at 32° C. or higher for 1 hour or more after the adding the seed crystal, and then,
decreasing the temperature of the mixture to a temperature of 25° C. or lower at a rate in which a temperature decrease amount per hour is 15° C. or lower.

11. The method according to claim 1 , wherein the precipitating the crystal is carried out, while forced-flowing the mixture with a power required for stirring of 0.03 kw/m 3 or more per unit volume.

12. The method according to claim 1 , wherein the solution contains 1% by weight or more and 70% by weight or less of reduced coenzyme Q10.

13. The method according to claim 1 , further comprising solid-liquid separating the precipitated crystal and then drying the precipitated crystal at a temperature of 46° C. or higher.

14. The method according to claim 1 , which is carried out under a deoxygenated atmosphere.

15. The method according to claim 1 , which is carried out under industrial scale production.

Assignees

• Kaneka Corp

Inventors

• Yamaguchi Takao
• Kinoshita Koichi

Classifications

• C07C41/40 Primary

  by change of physical state, e.g. by crystallisation · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C43/23

  containing hydroxy or O-metal groups · CPC title