CN115028525A - Oxidized coenzyme Q10 crystal and crystallization method thereof - Google Patents
Oxidized coenzyme Q10 crystal and crystallization method thereof Download PDFInfo
- Publication number
- CN115028525A CN115028525A CN202210720065.8A CN202210720065A CN115028525A CN 115028525 A CN115028525 A CN 115028525A CN 202210720065 A CN202210720065 A CN 202210720065A CN 115028525 A CN115028525 A CN 115028525A
- Authority
- CN
- China
- Prior art keywords
- oxidized coenzyme
- crystal
- temperature
- coenzyme
- crystallizing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
- C07C46/10—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C50/00—Quinones
- C07C50/26—Quinones containing groups having oxygen atoms singly bound to carbon atoms
- C07C50/28—Quinones containing groups having oxygen atoms singly bound to carbon atoms with monocyclic quinoid structure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses an oxidized coenzyme Q10 crystal and a crystallization method thereof, belonging to the technical field of chemical engineering crystallization, and the oxidized coenzyme Q10 crystal is obtained by dissolving and crystallizing an oxidized coenzyme Q10 extract, and the product of the rectangular flake oxidized coenzyme Q10 obtained by the method has uniform particle size distribution, does not generate coalescence phenomenon, is easy to centrifugally separate, and is suitable for industrial production.
Description
Technical Field
The invention relates to a coenzyme Q10 crystal and a crystallization method thereof, in particular to an oxidized coenzyme Q10 crystal and a crystallization method thereof, belonging to the technical field of chemical engineering crystallization.
Background
Oxidized coenzyme Q10, chemical name is decene quinone, ubiquinone, coenzyme Q10, molecular formula of oxidized coenzyme Q10 is C 59 H 90 O 4 Molecular weight 863.36, CAS number 303-98-0, chemical formula as follows:
the chemical name is 2- (3, 7, 11, 15, 19, 23, 27, 31, 35, 39-decamethyl-2, 6, 10, 14, 18, 22, 26, 30, 34, 38-forty carbon decaalkenyl) -5, 6-dimethoxy-3-methyl-p-benzoquinone. It is a fat-soluble quinone compound existing in nature, has a structure similar to vitamin K, vitamin E and plastoquinone, participates in energy production and activation in human body cells, is the most effective antioxidant component for preventing arteriosclerosis formation, is yellow or pale yellow crystalline powder, is easily soluble in chloroform, benzene and carbon tetrachloride, is soluble in acetone and diethyl ether, is slightly soluble in ethanol, and is insoluble in water and methanol. The light is decomposed into red substances, and is stable to temperature and humidity.
At present, coenzyme Q10 products on the market are generally oxidized coenzyme Q10, coenzyme Q10 crystals are preliminarily studied in 1984 by Taishan mountain (Taishan mountain, discussion on crystallization process of coenzyme Q10, journal of biochemical drugs, 1984, 2, pp67-68), and coenzyme Q10 is obtained by crystallizing a coenzyme Q10 ethanol solution in a thermostat, namely naturally cooling to 40 ℃, slowly cooling to 30-33 ℃ and keeping the temperature constant, although the crystal morphology is good, the coenzyme Q10 has high solubility and low yield at 30-33 ℃.
The oxidized coenzyme Q10 was recrystallized from ethanol in Zhang-Yin (Zhang-Yin, coenzyme Q10, crystal process research, Master, Tianjin university, 2012), which was not ideal, although the crystal morphology was improved.
Crystallization of oxidized coenzyme Q10 by known crystallization methods found in the art can lead to agglomeration of coenzyme Q10, impure product or reduced yield, broad particle size distribution, and the like. Therefore, a new and suitable crystallization method needs to be invented to promote the industrial production of the oxidized coenzyme Q10 and simultaneously solve the problems of product degradation, yield reduction, wide particle size distribution and the like in the production.
Disclosure of Invention
In view of the above, the present invention provides a method for crystallizing oxidized coenzyme Q10 and a rectangular plate-like crystal obtained by the method, which is obtained by dissolving and crystallizing an oxidized coenzyme Q10 extract, wherein the product of the rectangular plate-like oxidized coenzyme Q10 obtained by the method has uniform particle size distribution, does not generate coalescence phenomenon, is easy to centrifugally separate, and is suitable for industrial production.
In order to achieve the purpose, the invention adopts the following technical scheme:
a crystal of oxidized coenzyme Q10 in the form of rectangular plate, which is prepared by the following steps:
(1) adding the oxidized coenzyme Q10 extract into an organic solvent, heating to 40-60 ℃, stirring for dissolving, filtering to remove impurities, and cooling for later use;
(2) adding seed crystals into the filtrate, and growing the crystals for 0.5-2.0 h;
(3) carrying out secondary cooling after the crystal growing is finished, wherein the secondary crystal growing is carried out for 0.5-2 h;
(4) filtering, washing and drying to obtain the oxidized coenzyme Q10 crystal.
On the basis of the technical scheme, the invention can be further improved as follows:
further, the proportion of the oxidized coenzyme Q10 extract to the organic solvent in the step (1) is 1: 4ml to 10ml, preferably 1 mg: 4ml to 8ml, and more preferably 1 mg: 5ml to 6 ml. The crystal appearance is not greatly influenced as long as the addition of a small amount of water is controlled within 10 percent; on the other hand, the crystal can grow slowly by slowing down the cooling rate in the crystal growing stage, so that a product with uniform particle size distribution is obtained.
Furthermore, the dissolving operation of adding the oxidized coenzyme Q10 extract into the alcohol solvent or the alcohol mixed solvent can be carried out at any appropriate temperature, but the temperature of the system is too high, and the coenzyme Q10 can be degraded, so the temperature is 40-60 ℃, and preferably 45-55 ℃.
Further, the organic solvent in the step (1) is an organic solvent containing alcohols.
Further, the stirring time in the step (1) is 20-60 min, preferably 15-30 min.
Furthermore, the addition amount of the seed crystal in the step (2) is 0.2-5% (the extract contains coenzyme Q10), preferably 0.2-3%, and more preferably 0.2-1%.
Further, the temperature of the crystal growing in the step (2) is 28-40 ℃, and preferably 32-35 ℃;
the time for growing the crystals is 0.5-2 h, preferably 0.5-1 h.
Further, in the step (3), the secondary cooling operation is that the temperature is reduced by 0.5-1 ℃ per hour for 3-6 hours, the temperature is reduced by 2 ℃ per hour for 1-2 hours, and the temperature is reduced by 2-3 ℃ per hour to 10-15 ℃. Preferably, the temperature is reduced by 0.5 ℃ per hour in the first 3 hours, then the temperature is reduced by 1 ℃ per hour for 2 hours, then the temperature is reduced by 2 ℃ per hour for 3 hours, and then the temperature is reduced by 3 ℃ per hour to 10-15 ℃.
Further, the washing in the step (4) is carried out by separating the obtained oxidized coenzyme Q10 crystal and washing with a washing solvent to remove impurities;
the vacuum drying operation is vacuum drying at a temperature of 30-40 ℃.
Further, the washing solvent is methanol, ethanol or isopropanol, preferably ethanol.
The method has the advantages that the oxidized coenzyme Q10 crystal obtained by the crystallization method has uniform particle size distribution, does not generate coalescence phenomenon, is easy to centrifugally separate, and is suitable for industrial production.
Drawings
FIG. 1 is an SEM photograph at 100 times of the crystals of oxidized coenzyme Q101 obtained in example 1 of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
Oxidized coenzyme Q10 crystal prepared by the following steps:
adding 250g of coenzyme Q10 extract into 1200ml of absolute ethyl alcohol and 300ml of isobutanol in a 2000ml three-necked bottle under stirring, heating to 55-60 ℃ for dissolving, filtering, pouring the filtrate into the 2000ml three-necked bottle, stirring and cooling to 35 ℃, adding 0.4g of seed crystal, stirring for 10-15 minutes for crystal growth, and growing the crystal for 1 hour; continuously cooling for 1 hour to 1 ℃ for 3 hours; then reducing the temperature by 2 ℃ for 1 hour and continuing for 2 hours; reducing the temperature by 3 ℃ for 1 hour, stabilizing the temperature by 11-12 ℃, centrifuging, leaching by 100ml of multiplied by 3 absolute ethyl alcohol, and drying at 35-40 ℃ to obtain 120g of coenzyme Q10 crystal with the purity of 98.08%.
Example 2
Oxidized coenzyme Q10 crystal prepared by the following steps:
adding 250g of coenzyme Q10 extract into 1000ml of absolute ethyl alcohol and 500ml of isopropanol in a 2000ml three-necked bottle under stirring, heating to 50-55 ℃ for dissolution, filtering, pouring the filtrate into the 2000ml three-necked bottle, stirring and cooling, cooling to 36 ℃, adding 0.4g of seed crystal, stirring for 10-15 minutes for crystallization, and growing the crystals for 1 hour; continuously cooling for 1 hour to 1 ℃ for 3 hours; then reducing the temperature by 2 ℃ for 1 hour and continuing for 2 hours; reducing the temperature by 3 ℃ for 1 hour, stabilizing the temperature by 11-12 ℃ finally, centrifuging, leaching with 100ml of 3 times of absolute ethyl alcohol, and drying at 35-40 ℃ to obtain 123g of coenzyme Q10 crystal with the purity of 98.16%.
Example 3
Oxidized coenzyme Q10 crystal prepared by the following steps:
adding 250g of coenzyme Q10 extract into 1000ml of absolute ethyl alcohol and 500ml of n-propyl alcohol in a 2000ml three-necked bottle under stirring, heating to 50-55 ℃ for dissolution, filtering, pouring the filtrate into the 2000ml three-necked bottle, stirring and cooling, cooling to 36 ℃, adding 0.4g of seed crystal, stirring for 10-15 minutes for crystallization, and growing the crystals for 1 hour; continuously cooling for 1 hour to 1 degree for 3 hours; then reducing the temperature by 2 ℃ within 1 hour for 2 hours; reducing the temperature by 3 ℃ for another 1 hour, finally stabilizing the temperature by 11-12 ℃, centrifuging, leaching by 100ml of 3 times of absolute ethyl alcohol at 35-40 ℃, and drying to obtain 117g of coenzyme Q10 crystals with the purity of 98.28%.
Example 4
Oxidized coenzyme Q10 crystal prepared by the following steps:
adding 1500ml of n-propanol into a 2000ml three-necked bottle, stirring and adding 250g of coenzyme Q10 extract, heating to 50-55 ℃ for dissolution, filtering, pouring the filtrate into the 2000ml three-necked bottle, stirring and cooling, cooling to 30 ℃, adding 0.4g of seed crystal, stirring for 10-15 minutes for crystal growth, and growing the crystal for 1 hour; continuously cooling for 1 hour to 1 ℃ for 3 hours; then reducing the temperature by 2 ℃ for 1 hour and continuing for 2 hours; and reducing the temperature for 1 hour to 3 ℃, finally stabilizing the temperature for 11-12 ℃, centrifuging, leaching with 100ml of 3 times of absolute ethyl alcohol at 35-40 ℃, and drying to obtain 116g of coenzyme Q10 crystal with the purity of 98.35%.
Example 5
Oxidized coenzyme Q10 crystal prepared by the following steps:
adding 1500ml of isopropanol into a 2000ml three-necked bottle, adding 250g of coenzyme Q10 extract while stirring, heating to 50-55 ℃ for dissolving, and filtering. Pouring the filtrate into a 2000ml three-necked bottle, stirring and cooling, cooling to 31 ℃, adding 0.4g of seed crystal, stirring for 10-15 minutes to obtain crystal, and growing the crystal for 1 hour; continuously cooling for 1 hour to 1 ℃ for 3 hours; then reducing the temperature by 2 ℃ for 1 hour and continuing for 2 hours; reducing the temperature by 3 ℃ for 1 hour, stabilizing the temperature by 11-12 ℃, centrifuging, leaching by 100ml of 3 times of absolute ethyl alcohol, and drying at 35-40 ℃ to obtain 118g of coenzyme Q10 crystal with the purity of 98.37%.
Example 6
Oxidized coenzyme Q10 crystal prepared by the following steps:
adding 1500ml of n-butyl alcohol into a 2000ml three-necked bottle, adding 250g of coenzyme Q10 extract while stirring, heating to 50-55 ℃ for dissolving, and filtering. Pouring the filtrate into a 2000ml three-necked bottle, stirring and cooling, cooling to 29 ℃, adding 0.4g of seed crystal, stirring for 10-15 minutes to obtain crystal, and growing the crystal for 1 hour; continuously cooling for 1 hour to 1 ℃ for 3 hours; then reducing the temperature by 2 ℃ for 1 hour and continuing for 2 hours; reducing the temperature by 3 ℃ for 1 hour, stabilizing the temperature by 11-12 ℃ finally, centrifuging, leaching by 100ml of multiplied by 3 absolute ethyl alcohol at 35-40 ℃, and drying to obtain 118g of coenzyme Q10 crystal with the purity of 98.54%.
Example 7
Oxidized coenzyme Q10 crystal prepared by the following steps:
adding 1500ml of n-amyl alcohol into a 2000ml three-necked bottle, adding 250g of coenzyme Q10 extract while stirring, heating to 50-55 ℃ for dissolution, and filtering. Pouring the filtrate into a 2000ml three-necked bottle, stirring and cooling, cooling to 27 ℃, adding 0.4g of seed crystal, stirring for 10-15 minutes to obtain crystal, and growing the crystal for 1 hour; continuously cooling for 1 hour to 1 degree for 3 hours; then reducing the temperature by 2 ℃ for 1 hour and continuing for 2 hours; reducing the temperature by 3 ℃ for 1 hour, stabilizing the temperature by 11-12 ℃ finally, centrifuging, leaching with 100ml of 3 times of absolute ethyl alcohol, and drying at 35-40 ℃ to obtain 115g of coenzyme Q10 crystal with the purity of 98.62%.
Claims (10)
1. A method for crystallizing oxidized coenzyme Q10, which is characterized by comprising the following steps:
(1) adding the oxidized coenzyme Q10 extract into an organic solvent, heating to 40-60 ℃, stirring for dissolving, filtering to remove impurities, and cooling for later use;
(2) adding seed crystals into the filtrate, and growing the crystals for 0.5-2.0 h;
(3) carrying out secondary cooling after the crystal growing is finished, wherein the secondary crystal growing is carried out for 0.5-2 h;
(4) filtering, washing and drying to obtain the oxidized coenzyme Q10 crystal.
2. The method for crystallizing oxidized coenzyme Q10 according to claim 1, wherein the ratio of the oxidized coenzyme Q10 extract to the organic solvent in step (1) is 1 mg: 4ml to 10 ml.
3. The method for crystallizing oxidized coenzyme Q10 according to claim 1, characterized in that the organic solvent in step (1) is an alcohol-containing organic solvent.
4. The method for crystallizing oxidized coenzyme Q10 according to claim 1, wherein the stirring time in step (1) is 20 to 60 min.
5. The method for crystallizing oxidized coenzyme Q10 according to claim 1, characterized in that the seed crystal is added in an amount of 0.2 to 5% in step (2).
6. The method for crystallizing oxidized coenzyme Q10 according to claim 1, wherein the temperature for crystal growth in step (2) is 28 to 40 ℃.
7. The method for crystallizing oxidized coenzyme Q10 according to claim 1, wherein the secondary temperature reduction in step (3) is performed by reducing the temperature by 0.5-1 ℃ per hour for 3-6 hours, reducing the temperature by 2 ℃ per hour for 1-2 hours, and reducing the temperature by 2-3 ℃ per hour to 10-15 ℃.
8. The method for the crystallization of oxidized coenzyme Q10 according to claim 1, characterized in that the washing in step (4) is carried out by separating the obtained oxidized coenzyme Q10 crystals and then washing with a washing solvent to remove impurities;
the vacuum drying operation is vacuum drying at a temperature of 30-40 ℃.
9. The method of crystallizing oxidized coenzyme Q10 according to claim 8, characterized in that the washing solvent is methanol, ethanol or isopropanol.
10. A crystal of oxidized coenzyme Q10 obtained by the crystallization method according to any one of claims 1 to 9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210720065.8A CN115028525A (en) | 2022-06-23 | 2022-06-23 | Oxidized coenzyme Q10 crystal and crystallization method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210720065.8A CN115028525A (en) | 2022-06-23 | 2022-06-23 | Oxidized coenzyme Q10 crystal and crystallization method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115028525A true CN115028525A (en) | 2022-09-09 |
Family
ID=83126288
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210720065.8A Pending CN115028525A (en) | 2022-06-23 | 2022-06-23 | Oxidized coenzyme Q10 crystal and crystallization method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115028525A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1931819A (en) * | 2006-10-09 | 2007-03-21 | 昆明通发实业有限公司 | Coenzyme Q10 purifying process |
| CN104402697A (en) * | 2014-10-11 | 2015-03-11 | 天津大学 | Ultrasonic-assisted coenzyme Q10 crystallizing method |
| CN107337593A (en) * | 2017-07-24 | 2017-11-10 | 宁夏金维制药股份有限公司 | A kind of preparation method of Co-Q10 sterling |
| CN113754526A (en) * | 2021-09-27 | 2021-12-07 | 神舟生物科技有限责任公司 | High-purity coenzyme Q10 purification process |
-
2022
- 2022-06-23 CN CN202210720065.8A patent/CN115028525A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1931819A (en) * | 2006-10-09 | 2007-03-21 | 昆明通发实业有限公司 | Coenzyme Q10 purifying process |
| CN104402697A (en) * | 2014-10-11 | 2015-03-11 | 天津大学 | Ultrasonic-assisted coenzyme Q10 crystallizing method |
| CN107337593A (en) * | 2017-07-24 | 2017-11-10 | 宁夏金维制药股份有限公司 | A kind of preparation method of Co-Q10 sterling |
| CN113754526A (en) * | 2021-09-27 | 2021-12-07 | 神舟生物科技有限责任公司 | High-purity coenzyme Q10 purification process |
Non-Patent Citations (1)
| Title |
|---|
| 赵胤: "辅酶Q10结晶过程研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》, no. 05, pages 016 - 178 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9321770B2 (en) | Crystals of pyrroloquinolinequinone sodium salts | |
| EP2069363B1 (en) | Rifaximin in an amorphous form | |
| JP6321735B2 (en) | Crystal form of ertapenem sodium and process for its preparation | |
| WO2021161807A1 (en) | Method for producing reduced coenzyme q10 form ii crystals | |
| US20030028054A1 (en) | Synthesis of coenzyme q10 ubiquinone | |
| US10981854B2 (en) | Method for purification of 4-hydroxyacetophenone | |
| CN110305080A (en) | A kind of purification process of docetaxel | |
| JP2010528059A (en) | Process for producing stable, amorphous calcium salt of (6S) -N (5) -methyl-5,6,7,8-tetrahydrofolic acid | |
| CN115028525A (en) | Oxidized coenzyme Q10 crystal and crystallization method thereof | |
| CN100584845C (en) | Method for preparing (+)-(S-)-clopidogrel hydrosulfate high melting point crystal I | |
| CN115537932B (en) | High-cadmium-doped core-shell Au16Cd16(SR)20Cluster and preparation method thereof | |
| CN113402365B (en) | Preparation method of cannabidiol crystals | |
| CN114292203A (en) | Preparation method of DL-panthenol | |
| JP2003533529A (en) | Purification method of clavulanate | |
| JP2017031126A (en) | Method for producing pyrrolo-quinoline quinone crystal | |
| JP4200593B2 (en) | Crystalline L-ascorbic acid-2-phosphate sodium salt and process for producing the same | |
| CN104119312A (en) | Synthetic method of 25-hydroxy vitamin D3 | |
| CN115246768B (en) | Method for extracting menaquinone from wastewater from vitamin K3 production | |
| CN115385786B (en) | Method for synthesizing vitamin K2 | |
| CN107501327B (en) | Cyclophosphamide-water object method for crystallising | |
| CN113861164B (en) | Crystallization preparation method of nicotine | |
| WO2022202214A1 (en) | Production method for reduced coenzyme q10 form-ii type crystal or crystalline solid thereof | |
| CN117720606A (en) | Method for recycling testosterone mother liquor | |
| CN111138434A (en) | Preparation method of levofolinic acid | |
| US6271397B1 (en) | L-ascorbic acid-2-phosphoric acid potassium crystal and method for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |