Method of stabilizing reduced coenzyme q10
View Patent ↗The present invention provides a stabilization method, a preservation method and the like method of reduced coenzyme Q 10 , which is useful as functional nutritive foods, specific health foods and the like. Furthermore, the present invention provides a method for efficiently obtaining reduced coenzyme Q 10 of high quality and by a method suitable for a commercial production. It is possible to handle and stably preserve reduced coenzyme Q 10 under a condition that oxidation by a molecular oxygen is inhibited by contacting reduced coenzyme Q 10 with an ascorbic acid and citric acid or a related compound thereof, and thus a stabilized composition is obtained. Moreover, reduced coenzyme Q 10 is converted into a crystalline state in such a condition that the formation of oxidized coenzyme Q 10 as a byproduct is minimized by crystallizing reduced coenzyme Q 10 in the presence of ascorbic acid or a related compound thereof, etc., and thus a reduced coenzyme Q 10 crystal of high quality is produced. Furthermore, by successively crystallizing the generated reduced coenzyme Q 10 , in the presence of ascorbic acid or related compound thereof after reducing oxidized coenzyme Q 10 to reduced coenzyme Q 10 using ascorbic acid or a related compound thereof, operations are simplified and minimized, and thus reduced coenzyme Q 10 of high quality is produced.
1. A method of producing reduced coenzyme Q 10 crystal which comprises the steps of:
providing a reduced coenzyme Q 10 ;
successively crystallizing said reduced coenzyme Q 10 in a solvent in the presence of a citric acid or a related compound thereof and/or an ascorbic acid or a related compound thereof; and
recovering said reduced coenzyme Q 10 crystal;
wherein the solvent to be used is at least one species selected from the group consisting of hydrocarbons, monohydric alcohols, dihydric alcohols, trihydric alcohols, ketones, nitrogen compounds, sulfur-containing compounds and water, and the amount of the above solvents is 50% by weight or more in a whole mixture, and wherein crystallization is carried out under forced flowing at a stirring power consumption per unit volume of 0.01 kW/m 3 or more.
2. The method according to claim 1 , wherein the citric acid or a related compound thereof is at least one species selected from the group consisting of citric acid, and an ester and a salt thereof.
3. The method according to claim 1 , wherein the citric acid or a related compound thereof exists in an amount of 0.01 parts by weight or more relative to 100 parts by weight of a solvent.
4. The method according to claim 1 , wherein the ascorbic acid or a related compound thereof is at least one species selected from the group consisting of ascorbic acid, rhamno-ascorbic acid, arabo-ascorbic acid, gluco-ascorbic acid, fuco-ascorbic acid, glucohepto-ascorbic acid, xylo-ascorbic acid, galacto-ascorbic acid, gulo-ascorbic acid, allo-ascorbic acid, erythro-ascorbic acid, 6-desoxyascorbic acid, and an ester and a salt thereof.
5. The method according to claim 1 , wherein the ascorbic acid or a related compound thereof exists in an amount of 0.01 parts by weight or more relative to 100 parts by weight of a solvent.
6. The method according to claim 1 , wherein the solvent is a mono- or dihydric alcohol and/or a water-soluble solvent other than alcohols.
7. The method according to claim 6 , wherein the mono- or dihydric alcohol and/or the water-soluble solvent other than alcohols is used as a mixed solvent comprising the mono- or dihydric alcohol and/or the water-soluble organic solvent other than alcohols and water, and the mono- or dihydric alcohol and/or the water-soluble organic solvent is contained in 90 to 99.5% by weight in the mixed solvent.
8. The method according to claim 6 , wherein the mono- or dihydric alcohol and/or the water-soluble solvent other than alcohols is ethanol, acetone or a mixture thereof.
9. The method according to claim 1 , wherein the solvent is at least one species selected from the group consisting of hydrocarbons and nitriles.
10. The method according to claim 1 , wherein crystallization is carried out by at least one operation selected from the group consisting of cooling, concentration, solvent substitution or use of a poor solvent singly or in combination of two or more.
11. The method according to claim 10 , wherein a crystallization temperature is 25° C. or below.
12. The method according to claim 10 , wherein crystallization is carried out using cooling crystallization singly or in combination.
13. The method according to claim 12 , wherein a cooling rate is 40° C./hour or lower.
14. The method according to claim 1 , wherein reduced coenzyme Q 10 is crystallized at a concentration that 1 part by weight or more of reduced coenzyme Q 10 is contained relative to 100 parts by weight of a solvent.
15. The method according to claim 14 , wherein reduced coenzyme Q 10 is crystallized at a concentration that 5 to 10 parts by weight of reduced coenzyme Q 10 is contained relative to 100 parts by weight of a solvent.
16. The method according to claim 1 , wherein a seed crystal is added in crystallization.
17. The method according to claim 1 , which is carried out under a deoxidized atmosphere.
18. The method according to claim 1 , wherein an impurity is removed into a mother liquor.
19. The method according to claim 18 , wherein the impurity to be removed is at least one species elected from the group consisting of reduced coenzyme Q 9 , reduced coenzyme Q 8 and reduced coenzyme Q 7 .
20. The method according to claim 1 , wherein oxidized coenzyme Q 10 is provided, said oxidized coenzyme Q 10 is reduced to a reduced coenzyme Q 10 with ascorbic acid or a related compound thereof; said reduced coenzyme Q 10 is successively crystallized in the solvent in the presence of a citric acid or a related compound thereof and/or an ascorbic acid or a related compound thereof; and said reduced coenzyme Q 10 crystal is recovered.
21. The method according to claim 20 , wherein the ascorbic acid or a related compound thereof is at least one species selected from the group consisting of ascorbic acid, rhamno-ascorbic acid, arabo-ascorbic acid, gluco-ascorbic acid, fuco-ascorbic acid, glucohepto-ascorbic acid, xylo-ascorbic acid, galacto-ascorbic acid, gulo-ascorbic acid, allo-ascorbic acid, erythro-ascorbic acid, 6-desoxyascorbic acid, and an ester and a salt thereof.
22. The method according to claim 20 , wherein the amount of the ascorbic acid or a related compound thereof used in a reduction reaction is an effective amount that oxidized coenzyme Q 10 can be converted to reduced coenzyme Q 10 .
23. The method according to claim 22 , wherein the effective amount is 1 mole or more per mole of oxidized coenzyme Q 10 .
24. The method according to claim 20 , wherein reduction is carried out under coexistence of a basic substance or bisulfite.
25. The method according to claim 20 , wherein the citric acid or a related compound thereof and/or the ascorbic acid or a related compound thereof exists in an amount of 0.01 parts by weight or more relative to 100 parts by weight of a solvent in crystallization.
26. The method according to claim 20 , wherein the solvent to be used is a mono- or dihydric alcohol and/or a water-soluble solvent other than alcohols.
27. The method according to claim 26 , wherein crystallization is carried out in a mixed solvent comprising the mono-or dihydric alcohol and/or the water-soluble organic solvent other than alcohols and water, and the mono- or dihydric alcohol and/or the water-soluble organic solvent is contained in 90 to 99.5% by weight in the mixed solvent.
28. The method according to claim 26 , wherein the mono- or dihydric alcohol and/or the water-soluble solvent other than alcohols is ethanol, acetone, water or a mixture thereof.
29. The method according to claim 28 , wherein a crystallization temperature is 25° C. or below.
30. The method according to claim 20 , wherein a reduction reaction is carried out at 30° C. or higher, and then crystallization is carried out at 25° C. or below.
31. The method according to claim 20 , wherein crystallization is carried out using cooling crystallization singly or in combination.
32. The method according to claim 31 , wherein a cooling rate in the cooling crystallization is 40° C./hour or lower.
33. The method according to claim 20 , which is carried out under a deoxidized atmosphere in the reduction reaction and/or crystallization.
34. The method according to claim 20 , wherein an impurity is removed into a mother liquor.
35. The method according to claim 34 , wherein the impurity to be removed is at least one species selected from the group consisting of reduced coenzyme Q 9 , reduced coenzyme Q 8 and reduced coenzyme Q 7 .