CN108218681B - Method for purifying coenzyme Q10 - Google Patents
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Abstract
The invention discloses a coenzyme Q10 purification method, which comprises the steps of dissolving a coenzyme Q10 crude extract, adsorbing, eluting and removing impurities, and collecting eluent to obtain purified coenzyme Q10, wherein an adsorbing material in adsorption is selected from organic hydrocarbon bonded silica gel or organic hydrocarbon bonded silica gel containing polar organic functional groups, the adsorbing material has an anti-Langmuir isothermal adsorption property in the purification of coenzyme Q10, and the adsorption temperature is 30-65 ℃. The method can obtain the coenzyme Q10 monomer with the purity of more than 99.7 percent, the yield can reach 90 percent at most, meanwhile, the adsorbing material can be reused hundreds to thousands of times, the process is stable, the industrial production automation is easy to realize, the adsorbing material can be regenerated and used after being used, and the damage to the environment is greatly reduced.
Description
Technical Field
The invention relates to the technical field of separation and purification, and particularly relates to a purification process for preparing high-purity coenzyme Q10.
Background
Coenzyme Q10(Coenzyme Q10), also known as ubiquinone, is a fat-soluble quinone compound existing in nature, and has a structure similar to that of vitamin K, vitamin E and plastoquinone. Coenzyme Q10 is present in eukaryotic cells, especially mitochondria. Coenzyme Q10 is one of respiratory chain components, has a far higher content in the inner membrane of mitochondria than other respiratory chain components, has high fluidity on the inner membrane due to fat solubility, and is particularly suitable to be used as a flowing electron transporter.
Coenzyme Q10 has been reported to have various physiological functions, such as helping to provide sufficient oxygen to the heart muscle, preventing sudden heart disease; effectively prevent skin photoaging and reduce wrinkles around eyes; for the prevention and treatment of chronic fatigue syndrome; promoting energy conversion, improving immunity, improving energy, etc. Therefore, the coenzyme Q10 is widely applied to the fields of medicines, food additives, health care and the like.
The production method of coenzyme Q10 mainly comprises a chemical synthesis method, a plant cell culture method and a microbial fermentation method, but the improvement of the purity of coenzyme Q10 is the current difficulty.
CN105886562A discloses a method for preparing coenzyme Q10 by microbial fermentation, wherein the purification step comprises the steps of using a silica gel adsorption column for crude extraction, washing liquid with petroleum ether, eluting with diethyl ether-petroleum ether mixed liquid, and distilling the eluent under reduced pressure to obtain yellow oily substance crystals.
CN107337593A discloses a method for preparing a coenzyme Q10 pure product, which comprises the steps of extracting with petroleum ether, carrying out silica gel column chromatography, carrying out reduced pressure distillation and concentration on eluent, finally adding coenzyme Q10 seed crystal for crystallization, and carrying out reduced pressure drying to obtain the coenzyme Q10 pure product. Wherein the eluent is petroleum ether, the feeding speed is 2-5 BV/h, the elution speed is 1.5-3.5 BV/h, and the feeding temperature is 25-30 ℃.
CN103819326B discloses a method for separating and purifying coenzyme Q10 from microorganisms, which comprises a silica gel column adsorption process, wherein the adsorption temperature is 38-42 ℃, washing is carried out, and eluent is one or a combination of more than two of methanol, ethanol, ethylene glycol, isopropanol, n-butanol, ethyl acetate, petroleum ether and chloroform.
CN102391092B reports that coenzyme Q10 was purified using normal phase silica gel packing, and the eluent was one or more selected from the group consisting of ethanol-containing petroleum ether solution, ethanol-containing n-hexane solution, ethyl acetate-containing petroleum ether solution, ethyl acetate-containing n-hexane solution, acetone-containing petroleum ether solution, ethanol-containing cyclohexane solution, and isopropyl ether-containing cyclohexane solution.
CN101987815B discloses a purification process for preparing high-purity coenzyme Q10, which comprises the steps of adsorbing a coenzyme Q10 crude extract by using adsorption resin, eluting, concentrating, crystallizing, recrystallizing, then applying to a silica gel column, and purifying and refining by using a petroleum ether-ethyl ether or n-hexane-ethyl acetate mixed solvent as an eluent.
CN101111465A discloses a method for preparing pure coenzyme Q10 by separating a mixture containing coenzyme Q10 and the like by means of chromatography, wherein normal phase chromatography is recommended, preferably separation at a temperature ranging from about 20 to about 40 ℃.
Therefore, in the existing reports, silica gel is recommended to be used as an adsorption matrix to remove impurities, but the method has low selectivity and low yield, the silica gel can be reused, the using process is unstable, the sample loading amount and the collection mode of the silica gel used for purification each time need to be correspondingly adjusted, the industrial production cannot realize automatic production, and in addition, the silica gel can be regenerated, the cost is high, and the silica gel needs to be discarded after being used, so that the serious environmental pollution problem is caused.
In order to overcome the defects of the prior art, the invention provides a method for purifying coenzyme Q10.
Disclosure of Invention
The invention provides a method for purifying coenzyme Q10, which has stable process, is easy for automation of industrial production and is green and environment-friendly, and solves the defects of low selectivity and low yield when a normal phase silica gel material is adopted to purify coenzyme Q10.
The method for purifying the coenzyme Q10 comprises the following steps: dissolving the crude extract of coenzyme Q10, adsorbing and eluting to remove impurities, collecting eluent to obtain purified coenzyme Q10, wherein the adsorbing material in the adsorption is selected from organic hydrocarbon bonded silica gel or organic hydrocarbon bonded silica gel containing polar organic functional groups, the adsorbing material has the anti-Langmuir isothermal adsorption property in the purification of coenzyme Q10, and the adsorption temperature is 30-65 ℃.
The organic hydrocarbons in the adsorbent material of the present invention include, but are not limited to, octadecyl (C18), dodecyl (C12), octyl (C8), hexyl (C6), butyl (C4), ethyl (C2), phenyl, substituted phenyl, and cyclohexyl.
The polar organic functional group of the present invention includes, but is not limited to, ester group, amino group, amide group, and urea group.
It will be appreciated by those skilled in the art that the adsorbent material according to the present invention has inverse langmuir isothermal adsorption properties, unlike conventional silica gel materials (the adsorption properties of which are shown in figures a and C). The anti-langmuir isothermal adsorption property of the present invention means that no tailing of the main peak of coenzyme Q10 occurs upon purification of coenzyme Q10, as shown in figures B and D. Therefore, the adsorbing material can effectively enrich the coenzyme Q10 component, greatly improve the sample loading amount of the separating material and the recovery rate of high-purity components, particularly remove the components which are stronger than the main component in the adsorption and purification process to be less than 0.1 percent, and also remove the components which are weaker than the main component.
The adsorbing material can be a single bonded silica gel, and also can be a physical mixture of more than two bonded silica gels. For example, the adsorbent material is a physical mixture of octadecyl-bonded silica gel and octyl-bonded silica gel, NH2-a physical mixture of modified octadecyl-bonded silica gel and octyl-bonded silica gel, and the like. When the two or more bonded silica gels are physically mixed, the ratio of each bonded silica gel is arbitrary.
The adsorbing material can be organic hydrocarbon bonded silica gel, and can also be more than two organic hydrocarbon bonded silica gels. For example, the adsorbing material is silica gel doubly bonded by octadecyl and octyl. In a specific embodiment of the invention, the adsorbing material is silica gel doubly bonded by octadecyl and octyl, wherein the bonded octyl accounts for 12-92% of the bonded octadecyl by mass percent.
Preferably, the adsorbing material is silica gel bonded by one or a combination of two or more selected from octadecyl, octyl, butyl and ethyl.
In addition, the adsorption maintained at 30-65 ℃ in the invention is also a condition for ensuring that the adsorption material has reverse Langmuir isothermal adsorption property in the purification process, and when the temperature is lower than the temperature range in the invention, the adsorption process is damaged. More preferably, the adsorption temperature is 40-50 ℃, and most preferably, the adsorption temperature is 45 ℃.
In a preferred embodiment of the invention, the crude coenzyme Q10 extract is dissolved in a solvent selected from the group consisting of acetone/methanol, acetone/ethanol, methanol/ethanol, acetone/isopropanol, and methanol/isopropanol to provide a sample solution. More preferably, the solvent is acetone/methanol. The volume ratio of the acetone/methanol, acetone/ethanol or acetone/isopropanol solvent is (5-45)/(55-95), and the volume ratio of the methanol/isopropanol solvent is (60-96)/(4-40). Preferably, the acetone/methanol, acetone/ethanol or acetone/isopropanol solvent is (15-25)/(75-85) in volume ratio, and the methanol/isopropanol solvent is (80-95)/(5-20) in volume ratio. Particularly preferably, the acetone/methanol, acetone/ethanol or acetone/isopropanol solvent is 20/80 by volume ratio.
In a preferred embodiment of the present invention, the adsorption material is packed in an adsorption column. More preferably, the loading amount of the loading solution in the adsorption is 10 to 20 times of the column volume. Particularly preferably, the adsorption is performed by loading the loading solution into the adsorption column at a flow rate of 5 to 10 column volumes/hour, for example, the adsorption is performed by pumping the loading solution into the adsorption column at a flow rate of 5 to 10 column volumes/hour.
In a preferred embodiment of the invention, the eluent in the adsorption is selected from the group consisting of acetone/methanol, acetone/ethanol, methanol/ethanol, acetone/isopropanol and methanol/isopropanol. More preferably, the solvent is acetone/methanol, the volume ratio of acetone/methanol, acetone/ethanol or acetone/isopropanol is (5-45)/(55-95), and the volume ratio of methanol/isopropanol solvent is (60-96)/(4-40). Particularly preferably, the acetone/methanol, acetone/ethanol or acetone/isopropanol ratio is 20/80 by volume.
In a preferred embodiment of the invention, the elution flow rate in the adsorption is 5 to 10 column volumes/hour.
In a preferred embodiment of the invention, the amount of eluent used in the adsorption is 20 to 25 column volumes.
In a preferred embodiment of the present invention, the elution of the eluent in the adsorption is followed by elution with acetone for 1 to 2 column volumes. More preferably, the elution solution in the adsorption is eluted and then eluted by 1 column volume with acetone. It will be appreciated by those skilled in the art that the adsorbent material of the present invention is a renewable material and can be obtained by in-line acetone washing as described above. In one embodiment of the present invention, the adsorbent material is a regenerable adsorbent material, and the regeneration is obtained by off-line soaking in acetone.
In a preferred embodiment of the present invention, the collecting of the eluate is collecting the eluate in an amount of 8 to 23 column volumes to obtain purified coenzyme Q10. Preferably, the step of collecting the eluent is to collect the eluent with 15-23 times of column volume to obtain the purified coenzyme Q10. More preferably, the step of collecting the eluent is to collect 18 to 23 times of column volume of eluent to obtain the purified coenzyme Q10.
In a preferred embodiment of the invention, the crude extract of coenzyme Q10 is a product obtained by chemical synthesis, plant cell culture or microbial fermentation, and is purified by one or more methods selected from filtration, ion exchange or macroporous resin. Preferably, the crude extract of coenzyme Q10 is a product prepared by a microbial fermentation method and purified by one or more methods selected from filtration, ion exchange and macroporous resin.
In a preferred embodiment of the present invention, the method for purifying coenzyme Q10 further comprises concentrating the collected eluate, and drying, preferably, the concentration is performed by reduced pressure rotary evaporation.
In a preferred embodiment of the present invention, the method for purifying coenzyme Q10 further comprises a solvent recovery process.
In a preferred embodiment of the invention, the solvent is a preparative grade reagent.
In a specific embodiment of the present invention, the method for purifying coenzyme Q10 comprises: dissolving a crude extract of coenzyme Q10 in a solvent to obtain a loading solution, filling an adsorption material in an adsorption column, loading the loading solution in the adsorption column at a flow rate of 5-10 times of column volume per hour, wherein the loading amount is 10-20 times of the column volume, adding an eluent to adsorb and elute to remove impurities, and collecting the eluent to obtain purified coenzyme Q10, wherein the adsorption material in adsorption is selected from organic hydrocarbon bonded silica gel or organic hydrocarbon bonded silica gel containing polar organic functional groups, the adsorption material has an anti-Langmuir isothermal adsorption property in the purification of coenzyme Q10, and the adsorption temperature is 30-65 ℃.
In a specific embodiment of the present invention, the method for purifying coenzyme Q10 comprises:
dissolving coenzyme Q10 crude extract by using acetone/methanol with the volume ratio of 20/80 to obtain a sample solution, and pumping the sample solution into an adsorption column filled with an adsorption material at the flow rate of 5-10 times of column volume/hour, wherein the sample loading amount is 10-20 times of column volume;
eluting with 20/80 volume ratio acetone/methanol as eluent at flow rate of 5-10 times of column volume/hr for 20-25 times of column volume;
collecting eluent with 8-23 times of column volume to obtain purified coenzyme Q10, wherein the adsorbing material in adsorption is selected from organic hydrocarbon bonded silica gel or organic hydrocarbon bonded silica gel containing polar organic functional groups, the adsorbing material has anti-Langmuir isothermal adsorption property in the purification of coenzyme Q10, and the adsorption temperature is 30-65 ℃.
The coenzyme Q10 monomer with the purity of more than 99.7 percent can be obtained by adopting the purification method of the coenzyme Q10, the highest yield can reach 90 percent, and the yield of the high-purity monomer by adopting a silica gel adsorption method is only 5 to 10 percent. In particular, when octadecyl and octyl double bonded silica gel (C8/C18 ═ 12% to 92%) were used as the material, the yield of the high purity monomer was higher. Meanwhile, the adsorbing material can be reused hundreds of times to thousands of times, the process is stable, the automation of industrial production is very easy, the adsorbing material can be recycled after being simply treated after being used for 800 times and 1000 times, and the damage to the environment is greatly reduced.
Drawings
Figure 1 is a schematic of adsorption isotherms in an adsorption process, wherein a is a langmuir-type adsorption isotherm and B is a reverse langmuir-type adsorption isotherm. Cs represents the concentration of the separated species in the stationary phase and Cm represents the concentration of the separated species in the mobile phase.
Figure 2 is a schematic of the effluent peak during adsorption, where C is the langmuir-type adsorption isotherm and D is the inverse langmuir-type adsorption isotherm. t represents retention time and mAu represents detection signal strength.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood 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 obtained by a person skilled in the art without inventive effort based on the embodiments of the present invention, are within the scope of the present invention.
The term "and/or" is inclusive of the listed items as well as any number of combinations of items.
The term "comprising" is used in the open-ended description to encompass the recited specified ingredients or steps, as well as other specified ingredients or steps, that do not materially affect the performance of the invention.
The term "high purity" according to the present invention generally refers to a monomeric compound having a purity of greater than 99%, particularly to a monomeric compound having a purity of greater than 99.5%, and more particularly to a monomeric compound having a purity of greater than 99.7%.
The term "substituted phenyl" as used herein refers to phenyl substituted with one or more groups, particularly phenyl substituted with an alkyl group selected from C1-C6.
The terms "acetone/methanol", "ethanol/acetone", "methanol/ethanol", "isopropanol/acetone", "methanol/isopropanol" according to the invention refer to a combination of two substances, for example "acetone/methanol" refers to a combination of acetone and methanol in the proportions described herein.
Example 1
(1) Dissolving coenzyme Q10 crude extract by using acetone/methanol (20/80, v/v) to obtain a sample solution, and pumping the sample solution into an adsorption column filled with a C18 silica gel material at a flow rate of 8 times of column volume/hour, wherein the sample loading amount is 10 times of column volume;
(2) eluting with acetone/methanol (20/80, v/v) as eluent at flow rate of 5 times of column volume/hr for 25 times of column volume, and eluting with acetone for 1 time of column volume;
(3) collecting eluent with 18-23 times of column volume, wherein the eluent is a qualified purified coenzyme Q10 product, and collecting and combining all the rest eluents;
(4) concentrating the qualified product and other parts of eluent by adopting a reduced pressure rotary evaporation process, and condensing and recovering all the rotary evaporated liquid;
(5) the qualified product is subjected to suction filtration and air drying to obtain solid powder, and in the process, a dissolving solution, an eluent, a chromatographic column and a fraction receiving device are required to be kept in an environment of 45 +/-2 ℃;
(6) the qualified product is detected by a coenzyme Q10 detection method in 2015 pharmacopoeia, the yield of the coenzyme Q10 is 72%, and the purity is 99.7%.
Example 2
(1) Dissolving a crude coenzyme Q10 extract by using acetone/methanol (20/80, v/v) to obtain a loading solution, and pumping the loading solution into an adsorption column filled with C18 and C8 double-bonded (C8/C18 is 15-30%) silica gel materials at a flow rate of 8 times of column volume/hour, wherein the loading amount is 10 times of column volume;
(2) eluting with acetone/methanol (20/80, v/v) as mobile phase at flow rate of 5 times column volume/hr for 20 times column volume, and eluting with acetone for 1 time column volume;
(3) collecting eluent with the volume of 15-18 times of the column volume, wherein the eluent is a qualified purified coenzyme Q10 product, and collecting and combining all the rest eluents;
(4) concentrating the qualified product and other parts of eluent by adopting a reduced pressure rotary evaporation process, and condensing and recovering all the rotary evaporated liquid;
(5) the qualified product is subjected to suction filtration and air drying to obtain solid powder, and in the process, a dissolving solution, an eluent, a chromatographic column and a fraction receiving device are required to be kept in an environment of 45 +/-2 ℃;
(6) the qualified product is detected by a coenzyme Q10 detection method in 2015 pharmacopoeia, the yield of the coenzyme Q10 is 80%, and the purity of the coenzyme Q10 is 99.7%.
Example 3
(1) Dissolving a crude coenzyme Q10 extract by using acetone/methanol (20/80, v/v) to obtain a loading solution, and pumping the loading solution into an adsorption column filled with C18 and C8 double-bonded (C8/C18 is 60-90%) silica gel materials at a flow rate of 8 times of column volume/hour, wherein the loading amount is 10 times of column volume;
(2) eluting with acetone/methanol (20/80, v/v) as mobile phase at flow rate of 5 times column volume/hr for 22 times column volume, and eluting with acetone for 1 time column volume;
(3) collecting eluate 18-20 times of column volume, which is purified coenzyme Q10 qualified product, and collecting and mixing all the rest eluents;
(4) concentrating the qualified product and other parts of eluent by adopting a reduced pressure rotary evaporation process, and condensing and recovering all the rotary evaporated liquid;
(5) the qualified product is subjected to suction filtration and air drying to obtain solid powder, and in the process, a dissolving solution, an eluent, a chromatographic column and a fraction receiving device are required to be kept in an environment of 45 +/-2 ℃;
(6) the qualified product is detected by a coenzyme Q10 detection method in 2015 pharmacopoeia, the yield of the coenzyme Q10 is 90%, and the purity of the coenzyme Q10 is 99.7%.
Example 4
(1) Dissolving a coenzyme Q10 crude extract by using acetone/ethanol (13/87, v/v) to serve as a loading solution, and pumping the loading solution into an adsorption column filled with a C18 silica gel material and a C8 bonded silica gel material after physical mixing at a flow rate of 8 times of column volume/hour, wherein the loading amount is 10 times of column volume;
(2) eluting with acetone/ethanol (13/87, v/v) as mobile phase at flow rate of 5 times column volume/hr for 25 times column volume, and eluting with acetone for 1 time column volume;
(3) collecting eluent with 8-23 times of column volume, wherein the eluent is a qualified purified coenzyme Q10 product, and collecting and combining all the rest eluents;
(4) concentrating the qualified product and other parts of eluent by adopting a reduced pressure rotary evaporation process, and condensing and recovering all the rotary evaporated liquid;
(5) the qualified product is subjected to suction filtration and air drying to obtain solid powder, and in the process, a dissolving solution, an eluent, a chromatographic column and a fraction receiving device are required to be kept in an environment of 45 +/-2 ℃;
(6) the qualified product is detected by a coenzyme Q10 detection method in 2015 pharmacopoeia, the yield of the coenzyme Q10 is 87%, and the purity of the coenzyme Q10 is 99.8%.
Example 5
(1) The crude coenzyme Q10 extract was dissolved in acetone/isopropanol (25/75, v/v) as a loading solution, and the loading solution was pumped into a column packed with NH at a flow rate of 8 column volumes/hour2-loading the modified C18 silica gel material and the C8 bonded silica gel material in an adsorption column after physical mixing in a sample amount of 10 column volumes;
(2) eluting with acetone/isopropanol (25/75, v/v) as mobile phase at flow rate of 5 times column volume/hr for 25 times column volume, and eluting with acetone for 1 time column volume;
(3) collecting eluent with 8-20 times column volume, wherein the eluent is a qualified purified coenzyme Q10 product, and collecting and combining all the rest eluents;
(4) concentrating the qualified product and other parts of eluent by adopting a reduced pressure rotary evaporation process, and condensing and recovering all the rotary evaporated liquid;
(5) the qualified product is subjected to suction filtration and air drying to obtain solid powder, and in the process, a dissolving solution, an eluent, a chromatographic column and a fraction receiving device are required to be kept in an environment of 45 +/-2 ℃;
(6) the qualified product is detected by a coenzyme Q10 detection method in 2015 pharmacopoeia, the yield of the coenzyme Q10 is 88%, and the purity of the coenzyme Q10 is 99.7%.
Comparative example 1
(1) Dissolving coenzyme Q10 crude extract by using acetone/methanol (20/80, v/v) to serve as a sample loading solution, and pumping the sample loading solution into an adsorption column filled with a silica gel material at a flow rate of 8 times of column volume/hour, wherein the sample loading amount is 10 times of column volume;
(2) eluting with acetone/methanol (20/80, v/v) as mobile phase at flow rate of 5 times column volume/hr for 25 times column volume, and eluting with acetone for 1 time column volume;
(3) collecting eluent with 18-23 times of column volume, wherein the eluent is a qualified purified coenzyme Q10 product, and collecting and combining all the rest eluents;
(4) concentrating the qualified product and other parts of eluent by adopting a reduced pressure rotary evaporation process, and condensing and recovering all the rotary evaporated liquid;
(5) the qualified product is subjected to suction filtration and air drying to obtain solid powder, and in the process, a dissolving solution, an eluent, a chromatographic column and a fraction receiving device are required to be kept in an environment of 45 +/-2 ℃;
(6) the qualified product is detected by a coenzyme Q10 detection method in 2015 pharmacopoeia, the yield of the coenzyme Q10 is 10%, and the purity of the coenzyme Q10 is 99.0%.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and the like that are within the spirit and principle of the present invention are included in the present invention.
Claims (9)
1. A method for purifying coenzyme Q10, comprising: dissolving a crude extract of coenzyme Q10, adsorbing and eluting to remove impurities, and collecting an eluent to obtain purified coenzyme Q10, wherein the adsorbing material in adsorption is selected from organic hydrocarbon bonded silica gel or organic hydrocarbon bonded silica gel containing polar organic functional groups, and the adsorbing material has the anti-Langmuir isothermal adsorption property in the purification of coenzyme Q10, and the adsorption temperature is 30-65 ℃; the adsorption material is a physical mixture of more than two bonded silica gels or more than two organic hydrocarbon bonded silica gels; the organic hydrocarbon in the adsorbing material is selected from octadecyl, dodecyl, octyl, hexyl, butyl, ethyl, phenyl or cyclohexyl; the polar organic functional group is selected from ester group, amino group, amide group and carbamido group.
2. A method of purifying coenzyme Q10 according to claim 1, wherein the adsorbent material is a physical mixture of octadecyl-bonded silica gel and octyl-bonded silica gel or a physical mixture of NH 2-modified octadecyl-bonded silica gel and octyl-bonded silica gel.
3. The method for purifying coenzyme Q10 of claim 1, wherein the adsorbing material is silica gel doubly bonded by octadecyl and octyl.
4. The method for purifying coenzyme Q10 of any one of claims 1 to 3, wherein the adsorbent material is a regenerable adsorbent material, and the method further comprises regeneration of the adsorbent material, wherein the regeneration is obtained by off-line soaking or on-line washing with heated acetone.
5. The method for purifying coenzyme Q10 according to claim 1, wherein the adsorbing material is loaded in an adsorption column, the eluting solution in adsorption is selected from acetone/methanol, acetone/ethanol, methanol/ethanol, acetone/isopropanol and methanol/isopropanol, the eluting flow rate in adsorption is 5-10 times of column volume/hour, and the eluting solution in adsorption is 20-25 times of column volume.
6. The method for purifying coenzyme Q10, according to claim 5, wherein the step of collecting the eluate is a step of collecting an eluate 8 to 23 column volumes to obtain purified coenzyme Q10.
7. The method for purifying coenzyme Q10 according to claim 1, wherein the crude extract of coenzyme Q10 is a product obtained by chemical synthesis, plant cell culture or microbial fermentation, and is purified by one or more methods selected from filtration, ion exchange and macroporous resin adsorption.
8. A method for purifying coenzyme Q10, which is characterized by comprising the following steps: dissolving crude extract of coenzyme Q10 in solvent to obtain sample solution, loading an adsorption material in an adsorption column, loading the sample solution into the adsorption column at a flow rate of 5-10 times of column volume per hour, wherein the sample loading amount is 10-20 times of column volume, adding eluent to adsorb and elute to remove impurities, collecting the eluent to obtain purified coenzyme Q10, wherein the adsorption material is selected from organic hydrocarbon bonded silica gel or organic hydrocarbon bonded silica gel containing polar organic functional groups, the adsorption material has inverse Langmuir isothermal adsorption property in the purification of coenzyme Q10, the adsorption temperature is 30-65 ℃, the solvent is selected from acetone/methanol, ethanol/acetone, methanol/ethanol, isopropanol/acetone and methanol/isopropanol, and the eluent is selected from acetone/methanol, ethanol/acetone, methanol/ethanol, methanol/isopropanol/acetone and methanol/isopropanol, The adsorption material is physically mixed of more than two bonded silica gels or more than two organic hydrocarbon bonded silica gels; the organic hydrocarbon in the adsorbing material is selected from octadecyl, dodecyl, octyl, hexyl, butyl, ethyl, phenyl or cyclohexyl; the polar organic functional group is selected from ester group, amino group, amide group and carbamido group.
9. The method of claim 8 for purifying coenzyme Q10, comprising:
dissolving coenzyme Q10 crude extract by using acetone/methanol with the volume ratio of 20/80 to obtain a sample solution, and pumping the sample solution into an adsorption column filled with an adsorption material at the flow rate of 5-10 times of column volume/hour, wherein the sample loading amount is 10-20 times of column volume;
eluting with 20/80 volume ratio acetone/methanol as eluent at flow rate of 5-10 times of column volume/hr for 20-25 times of column volume;
collecting the eluent with 8-23 times of column volume to obtain the purified coenzyme Q10.
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| CN112920035A (en) * | 2019-12-06 | 2021-06-08 | 中国科学院大连化学物理研究所 | Method for removing Q11 impurity in coenzyme Q10 by using preparation chromatography |
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