CN110054565A - A kind of chromatographic purification method of High Purity Ethyl Eicosapentaenoate - Google Patents
A kind of chromatographic purification method of High Purity Ethyl Eicosapentaenoate Download PDFInfo
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- CN110054565A CN110054565A CN201910193003.4A CN201910193003A CN110054565A CN 110054565 A CN110054565 A CN 110054565A CN 201910193003 A CN201910193003 A CN 201910193003A CN 110054565 A CN110054565 A CN 110054565A
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- eicosapentaenoic acid
- ethyl ester
- acid ethyl
- purity
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- 229920000064 Ethyl eicosapentaenoic acid Polymers 0.000 title claims abstract description 64
- SSQPWTVBQMWLSZ-AAQCHOMXSA-N ethyl (5Z,8Z,11Z,14Z,17Z)-icosapentaenoate Chemical compound CCOC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC SSQPWTVBQMWLSZ-AAQCHOMXSA-N 0.000 title claims abstract description 64
- 238000000034 method Methods 0.000 title claims abstract description 21
- 229960002600 icosapent ethyl Drugs 0.000 title claims abstract description 20
- 238000011097 chromatography purification Methods 0.000 title claims abstract description 13
- 239000000945 filler Substances 0.000 claims abstract description 21
- 238000004366 reverse phase liquid chromatography Methods 0.000 claims abstract description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- 239000000523 sample Substances 0.000 claims description 16
- 238000000746 purification Methods 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- 230000006835 compression Effects 0.000 claims description 5
- 238000007906 compression Methods 0.000 claims description 5
- 238000001704 evaporation Methods 0.000 claims description 5
- 239000012488 sample solution Substances 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 235000020673 eicosapentaenoic acid Nutrition 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 6
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 7
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 7
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000011210 chromatographic step Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- BDNVAHNPDXGBIR-UHFFFAOYSA-N Amarin Natural products CC(=O)OCC(=C)C(=O)OC1CC(C)=CCCC(CO)=CC2OC(=O)C(=C)C12 BDNVAHNPDXGBIR-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 239000012716 precipitator Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/56—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
- C07C69/587—Monocarboxylic acid esters having at least two carbon-to-carbon double bonds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Fats And Perfumes (AREA)
Abstract
The present invention relates to medical pharmaceutical field, specifically a kind of chromatographic purification method of High Purity Ethyl Eicosapentaenoate.This method uses C18 reverse-phase chromatography filler, the eicosapentaenoic acid ethyl ester raw material of purity 70-80% is once purified and obtains the eicosapentaenoic acid ethyl ester of high-purity, cost is relatively low for it, yield is higher, EPA-EE purity produced can reach 99.5% or more, urgent need of the medical market to high-purity EPA E can be met, be conducive to industrial applications.
Description
Technical field
The present invention relates to medical pharmaceutical field, specifically a kind of chromatogram purification side of High Purity Ethyl Eicosapentaenoate
Method.
Background technique
Eicosapentaenoic acid (EPA) is one of several omega-3 type polyunsaturated fatty acids needed by human, treatment and
Prevention and treatment cardiovascular and cerebrovascular disease, inhibits tumour and prevention senile dementia etc. to all have preferable curative effect at inflammation.High-purity
Eicosapentaenoic acid ethyl ester (EPA-EE) can be used as a kind of bulk pharmaceutical chemicals, be applied to medical pharmaceutical field.Such as Irish biology system
The drug Vascepa that medicine company Amarin is developed is exactly the eicosapentaenoic acid ethyl ester (EPA-EE) for being greater than 96% using purity, is used
In treatment hypertriglyceridemia and dyslipidemia.Therefore, high-purity EPA E future will be widely used in bulk pharmaceutical chemicals
And medicine intermediate.
The current published main method for preparing EPA-EE have urea adduct crystallisation (United States Patent (USP) 6664405),
Metal salts as precipitator (United States Patent (USP) 6846942) and molecularly distilled (United States Patent (USP) 8889895), but above-mentioned most of method is also
It is the level for resting on pigment, cholesterol and a certain amount of saturated fatty acid in simple removal raw material fish oil, EPA-EE obtained
Purity is extremely difficult to 80% or more, is unable to satisfy high-purity requirement.For high-purity EPA E(97% or more) purifying preparation
Technology is few, and has respective defect.If Qing company utilizes the technology of silver nitrate diatomite chromatography EPA-EE, produce
Rate is less than 30%, and raw material needs to reach 90% or more purity, and furthermore there are heavy metal pollution risks for product；Domestic production method is more
Chromatogram purification EPA-EE is carried out using the preparative C18 reverse phase filler of Japanese great Cao or YMC company, but that there are material costs is high,
Chromatographic step is more, yield is not high, purity is difficult to the problems such as further increasing.As 102391112 A of CN uses YMC-Pack
ODS-AQ reverse phase filler carries out EPA-EE purification, but its raw material needs to reach 90% or more purity, and applied sample amount is also relatively low.CN
103833552 A refer to a kind of polymer reversed-phase resin for chromatographic step, but the resin is a large amount of organic molten using preceding needing
Agent and time are swollen, and there are monomer, crosslinking agent and pore-foaming agents etc. to remain risk, and in addition the process employs gradients to wash
De-, this is also unfavorable for industrial amplification.108640840 A of CN has invented a kind of multicolumn continuous chromatography method and has purified for EPA, but
This method needs complicated equipment and accurate instrument controlling, and equipment investment is larger.
Summary of the invention
The problem to be solved in the present invention is to provide a kind of chromatographic purification method of High Purity Ethyl Eicosapentaenoate, the colors
Spectrum purification process can once purify to obtain the eicosapentaenoic acid ethyl ester of high-purity, and cost is relatively low, and yield is higher, is conducive to
Industrial applications.
To solve the above problems, taking following technical scheme:
The characteristics of chromatographic purification method of High Purity Ethyl Eicosapentaenoate of the invention be the following steps are included:
A. the use of C18 reverse-phase chromatography filler is chromatogram purification filler, is dissolved with isopropanol, dress column homogenate is made；
B. dynamic axial compression column is loaded, 1800-2200psi is arranged in filling pressure, flows opposite chromatographic column with balance after installing
It is balanced；
C. the eicosapentaenoic acid ethyl ester solution of 70-80% is chosen as sample, 5 times is diluted with methanol solution, to UV detector
After baseline is steady, sample solution sample introduction；
D. continue to rinse chromatographic column with balance mobile phase after sample introduction, flush volume is no less than 10 column volumes；
E. the efflux for collecting the 9th column volume is eicosapentaenoic acid ethyl ester component, and collected volume is 0.8-1 times of cylinder
Product；
F. after the completion of eicosapentaenoic acid ethyl ester Fraction collection, chromatographic column is rinsed with pure methanol and is no less than 2 column volumes；
G. the chromatogram purification that c ~ f step can be carried out continuously eicosapentaenoic acid ethyl ester is repeated；
H. the eicosapentaenoic acid ethyl ester component collected to back is evaporated under reduced pressure, and temperature is 50 ~ 60 degree, in solution
After methanol content evaporating completely, High Purity Ethyl Eicosapentaenoate product is both obtained.
Wherein, the C18 reverse-phase chromatography filler selects Galaksil UP-C18H filler.
The methanol aqueous solution that the balance mobile phase is 85-88%, dosage are at least 2-3 times of column volume.
Above scheme is taken, is had the advantage that
The chromatographic purification method of High Purity Ethyl Eicosapentaenoate of the invention uses C18 reverse-phase chromatography filler, by purity 70-
80% eicosapentaenoic acid ethyl ester raw material, which once purifies, obtains the eicosapentaenoic acid ethyl ester of high-purity, and cost is relatively low, yield
Higher, EPA-EE purity produced can reach 99.5% or more, can meet medical market and be essential to the urgent of high-purity EPA E
It asks, is conducive to industrial applications.
Detailed description of the invention
Fig. 1: the chromatogram purification map of eicosapentaenoic acid ethyl ester, arrow show collection object；
Fig. 2: the gas chromatographic analysis figure of object, purity 99.94% are collected in embodiment 1；
Fig. 3: the gas chromatographic analysis figure of object, purity 99.92% are collected in embodiment 2；
Fig. 4: the gas chromatographic analysis figure of object, purity 99.82% are collected in embodiment 3.
Specific embodiment
The present invention is described in further details with reference to embodiments.
Embodiment one
The chromatographic purification method of the High Purity Ethyl Eicosapentaenoate of the present embodiment the following steps are included:
A. the use of C18 reverse-phase chromatography filler is chromatogram purification filler, is dissolved with isopropanol, dress column homogenate is made；
B. dynamic axial compression column is loaded, 1800psi is arranged in filling pressure, is carried out after installing with balance flowing chromatographic column relatively flat
Weighing apparatus；
C. the eicosapentaenoic acid ethyl ester solution of selection 70% dilutes 5 times with methanol solution, to UV detector base as sample
After line is steady, sample solution sample introduction；
D. continue to rinse chromatographic column with balance mobile phase after sample introduction, flush volume is no less than 10 column volumes；
E. separating spectrum such as Fig. 1, collecting efflux shown in arrow in the 9th column volume, that is, figure is eicosapentaenoic acid ethyl ester
Component, collected volume are 0.8 times of column volume；
F. after the completion of eicosapentaenoic acid ethyl ester Fraction collection, chromatographic column is rinsed with pure methanol and is no less than 2 column volumes；
G. the chromatogram purification that c ~ f step can be carried out continuously eicosapentaenoic acid ethyl ester is repeated；
H. the eicosapentaenoic acid ethyl ester component collected to back is evaporated under reduced pressure, and temperature is 50 degree, to the first in solution
After alcohol component evaporating completely, High Purity Ethyl Eicosapentaenoate product is both obtained, is tested by GC, purity 99.94%, such as schemed
Shown in 2.
Embodiment two
The chromatographic purification method of the High Purity Ethyl Eicosapentaenoate of the present embodiment the following steps are included:
A. the use of C18 reverse-phase chromatography filler is chromatogram purification filler, is dissolved with isopropanol, dress column homogenate is made；
B. dynamic axial compression column is loaded, 2000psi is arranged in filling pressure, is carried out after installing with balance flowing chromatographic column relatively flat
Weighing apparatus；
C. the eicosapentaenoic acid ethyl ester solution of selection 75% dilutes 5 times with methanol solution, to UV detector base as sample
After line is steady, sample solution sample introduction；
D. continue to rinse chromatographic column with balance mobile phase after sample introduction, flush volume is no less than 10 column volumes；
E. the efflux for collecting the 9th column volume is eicosapentaenoic acid ethyl ester component, and collected volume is 0.9 times of column volume；
F. after the completion of eicosapentaenoic acid ethyl ester Fraction collection, chromatographic column is rinsed with pure methanol and is no less than 2 column volumes；
G. the chromatogram purification that c ~ f step can be carried out continuously eicosapentaenoic acid ethyl ester is repeated；
H. the eicosapentaenoic acid ethyl ester component collected to back is evaporated under reduced pressure, and temperature is 55 degree, to the first in solution
After alcohol component evaporating completely, High Purity Ethyl Eicosapentaenoate product is both obtained, is tested by GC, purity 99.92%, such as schemed
Shown in 3.
Embodiment three
The chromatographic purification method of the High Purity Ethyl Eicosapentaenoate of the present embodiment the following steps are included:
A. the use of C18 reverse-phase chromatography filler is chromatogram purification filler, is dissolved with isopropanol, dress column homogenate is made；
B. dynamic axial compression column is loaded, 2200psi is arranged in filling pressure, is carried out after installing with balance flowing chromatographic column relatively flat
Weighing apparatus；
C. the eicosapentaenoic acid ethyl ester solution of selection 80% dilutes 5 times with methanol solution, to UV detector base as sample
After line is steady, sample solution sample introduction；
D. continue to rinse chromatographic column with balance mobile phase after sample introduction, flush volume is no less than 10 column volumes；
E. the efflux for collecting the 9th column volume is eicosapentaenoic acid ethyl ester component, and collected volume is 1 times of column volume；
F. after the completion of eicosapentaenoic acid ethyl ester Fraction collection, chromatographic column is rinsed with pure methanol and is no less than 2 column volumes；
G. the chromatogram purification that c ~ f step can be carried out continuously eicosapentaenoic acid ethyl ester is repeated；
H. the eicosapentaenoic acid ethyl ester component collected to back is evaporated under reduced pressure, and temperature is 60 degree, to the first in solution
After alcohol component evaporating completely, High Purity Ethyl Eicosapentaenoate product is both obtained, is tested by GC, purity 99.82%, such as schemed
Shown in 4.
In above-described embodiment, the C18 reverse-phase chromatography filler selects Galaksil UP-C18H filler；The balance flowing
It is mutually the methanol aqueous solution of 85-88%, dosage is at least 2-3 times of column volume.
The chromatographic purification method of High Purity Ethyl Eicosapentaenoate of the invention uses C18 reverse-phase chromatography filler, will be pure
The eicosapentaenoic acid ethyl ester raw material of degree 70-80% once purifies and obtains the eicosapentaenoic acid ethyl ester of high-purity, cost compared with
Low, yield is higher, and EPA-EE purity produced can reach 99.5% or more, can meet medical market to high-purity EPA E's
Urgent need is conducive to industrial applications.
Claims (3)
1. a kind of chromatographic purification method of High Purity Ethyl Eicosapentaenoate, it is characterised in that the following steps are included:
A. the use of C18 reverse-phase chromatography filler is chromatogram purification filler, is dissolved with isopropanol, dress column homogenate is made；
B. dynamic axial compression column is loaded, 1800-2200psi is arranged in filling pressure, flows opposite chromatographic column with balance after installing
It is balanced；
C. the eicosapentaenoic acid ethyl ester solution of 70-80% is chosen as sample, 5 times is diluted with methanol solution, to UV detector
After baseline is steady, sample solution sample introduction；
D. continue to rinse chromatographic column with balance mobile phase after sample introduction, flush volume is no less than 10 column volumes；
E. the efflux for collecting the 9th column volume is eicosapentaenoic acid ethyl ester component, and collected volume is 0.8-1 times of cylinder
Product；
F. after the completion of eicosapentaenoic acid ethyl ester Fraction collection, chromatographic column is rinsed with pure methanol and is no less than 2 column volumes；
G. the chromatogram purification that c ~ f step can be carried out continuously eicosapentaenoic acid ethyl ester is repeated；
H. the eicosapentaenoic acid ethyl ester component collected to back is evaporated under reduced pressure, and temperature is 50 ~ 60 degree, in solution
After methanol content evaporating completely, High Purity Ethyl Eicosapentaenoate product is both obtained.
2. the chromatographic purification method of High Purity Ethyl Eicosapentaenoate as described in claim 1, it is characterised in that the C18
Reverse-phase chromatography filler selects Galaksil UP-C18H filler.
3. the chromatographic purification method of High Purity Ethyl Eicosapentaenoate as described in claim 1, it is characterised in that described flat
The mobile phase that weighs is the methanol aqueous solution of 85-88%, and dosage is at least 2-3 times of column volume.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910193003.4A CN110054565A (en) | 2019-03-15 | 2019-03-15 | A kind of chromatographic purification method of High Purity Ethyl Eicosapentaenoate |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910193003.4A CN110054565A (en) | 2019-03-15 | 2019-03-15 | A kind of chromatographic purification method of High Purity Ethyl Eicosapentaenoate |
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| Publication Number | Publication Date |
|---|---|
| CN110054565A true CN110054565A (en) | 2019-07-26 |
Family
ID=67316893
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|---|---|---|---|
| CN201910193003.4A Pending CN110054565A (en) | 2019-03-15 | 2019-03-15 | A kind of chromatographic purification method of High Purity Ethyl Eicosapentaenoate |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020177728A1 (en) | 2019-03-05 | 2020-09-10 | 四川国为制药有限公司 | Fatty acid composition and application thereof |
| CN113698984A (en) * | 2021-08-27 | 2021-11-26 | 常熟纳微生物科技有限公司 | Separation and purification method of eicosapentaenoic acid in fish oil |
| CN113698296A (en) * | 2020-05-22 | 2021-11-26 | 中国科学院大连化学物理研究所 | A kind of method for C18 reverse phase silica gel purification EPA |
| CN113831244A (en) * | 2020-06-24 | 2021-12-24 | 北京创新通恒科技有限公司 | A kind of purifying high-purity EPA-ee separation equipment and process method |
| CN115015458A (en) * | 2022-07-01 | 2022-09-06 | 江苏汉邦科技股份有限公司 | Split-flow chromatography system and method for preparing ethyl eicosapentaenoate by using split-flow chromatography system |
| CN116655469A (en) * | 2022-02-18 | 2023-08-29 | 苏州纳微科技股份有限公司 | A method for the separation and purification of ethyl eicosapentaenoate by single-column semi-continuous chromatography |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020177728A1 (en) | 2019-03-05 | 2020-09-10 | 四川国为制药有限公司 | Fatty acid composition and application thereof |
| CN113698296A (en) * | 2020-05-22 | 2021-11-26 | 中国科学院大连化学物理研究所 | A kind of method for C18 reverse phase silica gel purification EPA |
| CN113831244A (en) * | 2020-06-24 | 2021-12-24 | 北京创新通恒科技有限公司 | A kind of purifying high-purity EPA-ee separation equipment and process method |
| CN113698984A (en) * | 2021-08-27 | 2021-11-26 | 常熟纳微生物科技有限公司 | Separation and purification method of eicosapentaenoic acid in fish oil |
| CN116655469A (en) * | 2022-02-18 | 2023-08-29 | 苏州纳微科技股份有限公司 | A method for the separation and purification of ethyl eicosapentaenoate by single-column semi-continuous chromatography |
| CN116655469B (en) * | 2022-02-18 | 2026-05-12 | 苏州纳微科技股份有限公司 | Method for separating and purifying eicosapentaenoic acid ethyl ester by single-column semicontinuous chromatography |
| CN115015458A (en) * | 2022-07-01 | 2022-09-06 | 江苏汉邦科技股份有限公司 | Split-flow chromatography system and method for preparing ethyl eicosapentaenoate by using split-flow chromatography system |
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