A kind of preparation method and application of eicosapentaenoic acid anisyl

Abstract

The present invention belongs to the technical field of pharmaceutical chemistry, and specifically relates to a preparation method and application of eicosapentaenoic acid anisyl. The preparation method of eicosapentaenoic acid anisyl provided by the present invention is to use 4-methoxybenzyl alcohol as an intermediate, and use a one-step reaction method to design and synthesize a novel eicosapentaenoic acid anisyl compound from eicosapentaenoic acid and 4-methoxybenzyl alcohol. The newly synthesized eicosapentaenoic acid anisyl compound of the present invention has the advantages of high bioavailability, small toxic and side effects, and good biocompatibility. In addition, the eicosapentaenoic acid anisyl provided by the present invention has a significant lipid-lowering effect, especially has a significant therapeutic effect on hyperlipidemia, and provides a new drug for hyperlipidemia.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical chemistry, and relates to a preparation method and application of an eicosapentaenoic acid derivative having the effect of lowering blood lipids, and specifically relates to a preparation method and application of eicosapentaenoic acid anisyl ester. Background Art

[0002] In recent years, the rapid development of social economy has brought about an improvement in people's living standards. However, this change is also accompanied by a change in dietary structure. High-fat, high-sugar diets are becoming increasingly common and have become one of the common dietary habits in modern life. Excessive intake of these high-energy-density foods can lead to increased blood lipids and blood sugar fluctuations, which in turn can cause the occurrence and aggravation of chronic diseases such as cardiovascular and cerebrovascular diseases. In this case, cardiovascular and cerebrovascular diseases have become one of the major diseases that seriously affect public health.

[0003] Studies have shown that ω-3 polyunsaturated fatty acids have multiple biological activities such as lowering triglycerides, improving blood lipid profiles, anti-inflammatory and antioxidant activities, and are expected to become an important means of preventing and treating cardiovascular and cerebrovascular diseases. The active ingredients in fish oil are mainly all-cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and all-cis-4,7,10,13,16,19-docosahexaenoic acid (DHA), both of which belong to the Omega-3 series of polyene long-chain fatty acids. Among them, EPA has been widely studied and proven to have significant potential in regulating lipid metabolism and improving cardiovascular health. In 2019, Clinical studies published by the team show that the combined use of EPA-EE and statins can reduce the relative risk of first major adverse cardiovascular events (MACE) by 25% compared with the use of statins alone. However, currently only the single-molecule prescription drug with active ingredient, eicosapentaenoic acid ethyl ester (EPA-EE, purity 96%) from Amarin, Ireland, has been approved by the US FDA for the treatment of hypertriglyceridemia and reduction of the risk of cardiovascular events.

[0004] At present, the most popular EPA preparations on the market are mainly ethyl ester EPA preparations. For example: Patent document CN102391112A discloses a method for industrial production of eicosapentaenoic acid ethyl ester. The method comprises: (a) using molecular distillation to increase the purity of EPA-EE in raw fish oil with a purity of 68% to 72% to 79% to 83%, with a yield of 50% to 70%; (b) using a chemical method of salt precipitation to separate the fish oil with a purity of 79% to 83% of EPA-EE obtained in step (a) by salt precipitation, so that the purity of EPA-EE therein is increased to 88% to 92%, and the yield is 50%; (c) using industrial preparative chromatography to purify the fish oil with a purity of 88% to 92% of EPA-EE obtained in step (b) by preparative chromatography, so that the purity of EPA-EE therein is increased to more than 96%. This method can obtain a production method of EPA-EE with a purity of more than 96%.

[0005] Patent document CN116396168A discloses a method for preparing ethyl eicosapentaenoic acid. The method comprises: S1, mixing fish oil raw materials with strong acid or strong base catalysts, reacting, then treating and stratifying the reaction solution, taking the upper layer liquid for elution, and obtaining a mixed solution of ethyl eicosapentaenoic acid and ethyl eicosapentaenoic acid; S2, purifying the mixed solution of ethyl eicosapentaenoic acid and ethyl eicosapentaenoic acid by supercritical extraction, and then entering the distillation tower for distillation and purification; S3, separating and purifying the ethyl eicosapentaenoic acid after distillation in S2 by high performance liquid chromatography separation, and obtaining ethyl eicosapentaenoic acid. The method has high purity of the final product, is green and environmentally friendly, has low production cost, and is suitable for large-scale preparation.

[0006] However, current EPA ethyl ester preparations generally have the disadvantages of low absorption rate in the human body and complex production process of high-purity preparations. Therefore, researching and developing a new method for preparing EPA derivatives with simple process and lipid-lowering effect is a difficulty that needs to be solved urgently. Summary of the invention

[0007] In order to solve the defects of the prior art, the present invention provides a method for preparing an eicosapentaenoic acid derivative with the effect of lowering blood lipids, and specifically provides a method for preparing eicosapentaenoic acid anisyl ester (EPA-ME) and its application. The eicosapentaenoic acid anisyl ester (EPA-ME) prepared by the present invention is easier to remove the prodrug group in the intestine, releases the active molecule EPA, and makes it more oral bioavailability, and has excellent biocompatibility, does not cause metabolic toxicity, and the eicosapentaenoic acid derivative has broad prospects for the development of innovative drugs.

[0008] The present invention provides a method for preparing eicosapentaenoic acid anisyl, comprising the following steps:

[0009] Step S1, adding 4-methoxybenzyl alcohol and eicosapentaenoic acid into a round-bottom flask containing tetrahydrofuran solution, stirring at room temperature for 4 to 6 minutes, then adding lipase into the system, stirring and reacting at 28 to 35° C. for 7 to 9 hours, filtering and taking a filter cake;

[0010] Step S2, washing the filter cake obtained in step S1 with petroleum ether for 3 to 4 times, collecting the filtrate, combining the filtrate, and performing reduced pressure distillation on the combined filtrate to obtain a light yellow transparent liquid;

[0011] Step S3, separating the light yellow transparent liquid obtained in step S2 by column chromatography, collecting corresponding components, and performing reduced pressure distillation to obtain a light yellow liquid product.

[0012] Furthermore, in the step S1, the molar ratio of 4-methoxybenzyl alcohol to eicosapentaenoic acid is 36.2 mmoL:39.7 mmoL, and the equivalent ratio of 4-methoxybenzyl alcohol to eicosapentaenoic acid is 1:1.1 (1:1.1 eq.).

[0013] Furthermore, in step S1, the material-liquid ratio of 4-methoxybenzyl alcohol to tetrahydrofuran solution is 1 g: (8-12) mL.

[0014] Furthermore, in step S1, the weight ratio of eicosapentaenoic acid to lipase is 4:(1-2).

[0015] Furthermore, the lipase in step S1 is Novozym 435 enzyme.

[0016] Furthermore, during the reaction process of step S1, thin layer chromatography is used to monitor the reaction, and the developing solvent of the thin layer chromatography is: petroleum ether / ethyl acetate = 9 / 1, Rf = 0.6.

[0017] Furthermore, in step S3, the mobile phase of the column chromatography is: petroleum ether / ethyl acetate = 24 / 1.

[0018] In addition, the present invention also provides eicosapentaenoic acid anisyl ester prepared by the preparation method of eicosapentaenoic acid anisyl ester.

[0019] Furthermore, the present invention also provides the use of the eicosapentaenoic acid anisyl in the preparation of a drug for preventing or treating hypolipidemic conditions.

[0020] Furthermore, the present invention also provides the use of the eicosapentaenoic acid anisyl in the preparation of a drug for preventing or treating hyperlipidemia.

[0021] 4-methoxybenzyl alcohol, also known as anise alcohol, anise alcohol, and p-methoxybenzyl alcohol, is commonly used in the food field and is a food flavoring. At present, studies have shown that 4-methoxybenzyl alcohol has the effects of protecting cells from oxidative damage and inhibiting apoptosis of nerve cells. 4-methoxybenzyl alcohol can be applied to the field of medicine and has attracted the attention of the inventor. In order to solve the technical problems of the cumbersome preparation process of the current eicosapentaenoic acid derivatives and the low absorption rate of the ethyl ester type EPA. After a large number of exploratory experiments, the inventor proposed a preparation method of a novel eicosapentaenoic acid (EPA) derivative, which specifically uses 4-methoxybenzyl alcohol as an intermediate, and uses a one-step reaction method to design and synthesize a novel eicosapentaenoic acid anisyl ester (EPA-ME) compound with EPA and 4-methoxybenzyl alcohol. Compared with the ethyl ester type EPA compound, the newly synthesized EPA-ME compound of the present invention is easier to remove the prodrug group in the intestine in terms of compound structure, releases the active molecule EPA, makes it more oral bioavailability, and has excellent biocompatibility, does not cause metabolic toxicity, has lower side effects and better therapeutic effects.

[0022] Compared with the prior art, the preparation method of eicosapentaenoic acid anisyl provided by the present invention has the following advantages:

[0023] (1) The preparation method of eicosapentaenoic acid anisyl provided by the present invention is easy to operate and has simple steps. The eicosapentaenoic acid derivative can be prepared in one step, and the prepared eicosapentaenoic acid derivative has the advantages of high bioavailability, low toxicity and side effects, and good biocompatibility.

[0024] (2) The eicosapentaenoic acid anisole prepared by the preparation method of the eicosapentaenoic acid anisole provided by the present invention has a significant lipid-lowering effect, especially has a significant therapeutic effect on hyperlipidemia, and provides a new drug for hyperlipidemia. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The synthetic route of eicosapentaenoic acid anise ester (EPA-ME) is shown in FIG.

[0026] Figure 2 Eicosapentaenoic acid anisyl (EPA-ME) 1 H spectrum.

[0027] Figure 3 Eicosapentaenoic acid anisyl (EPA-ME) 13 C spectrum.

[0028] Figure 4 Figure 3 shows the body weight of rats before and after treatment with different drug groups.

[0029] Figure 5Figure 3 shows the changes in body weight of rats after treatment with different drug groups.

[0030] Figure 6 This is a graph showing the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the serum of rats in different drug groups.

[0031] Figure 7 This is a graph showing the changes in the levels of SOD, MDA, ALT and AST in the serum of rats in different drug groups. DETAILED DESCRIPTION

[0032] The present invention is further described below by describing specific embodiments, but this is not a limitation of the present invention. Those skilled in the art can make various modifications or improvements based on the basic idea of ​​the present invention, but as long as they do not deviate from the basic idea of ​​the present invention, they are all within the scope of the present invention. The materials involved in the present invention are all food grade and can be obtained by commercial or conventional technical means in the art.

[0033] Example 1: A method for preparing eicosapentaenoic acid anisyl

[0034] Step S1, adding 5 g of 4-methoxybenzyl alcohol and 12 g of eicosapentaenoic acid into a round-bottom flask containing 50 mL of tetrahydrofuran solution, stirring at room temperature for 5 min, then adding 3 g of Novozym 435 enzyme into the system, stirring continuously for 8 h at 30° C., monitoring the reaction by thin layer chromatography during the reaction, wherein the developing solvent for the thin layer chromatography is: petroleum ether / ethyl acetate=9 / 1, Rf=0.6, filtering, and taking a filter cake;

[0035] Step S2, washing the filter cake obtained in step S1 with 10 mL of petroleum ether for 3 times, collecting the filtrate, combining the filtrate, and performing reduced pressure distillation on the combined filtrate to obtain a light yellow transparent liquid;

[0036] Step S3, separating the light yellow transparent liquid obtained in step S2 by column chromatography, wherein the mobile phase of the column chromatography is: petroleum ether / ethyl acetate = 24 / 1, collecting the corresponding components, and performing reduced pressure distillation to obtain a light yellow liquid product (EPA-ME).

[0037] Example 1 Synthetic route for preparing eicosapentaenoic acid anisyl Figure 1 shown.

[0038] Example 2: A method for preparing eicosapentaenoic acid anisyl

[0039] Step S1, adding 5 g of 4-methoxybenzyl alcohol and 12 g of eicosapentaenoic acid into a round-bottom flask containing 55 mL of tetrahydrofuran solution, stirring at room temperature for 4 min, then adding 4 g of Novozym 435 enzyme into the system, stirring continuously for 8 h at 28° C., monitoring the reaction by thin layer chromatography during the reaction, wherein the developing solvent for the thin layer chromatography is: petroleum ether / ethyl acetate=9 / 1, Rf=0.6, filtering, and taking a filter cake;

[0040] Step S2, washing the filter cake obtained in step S1 with 10 mL of petroleum ether for 3 times, collecting the filtrate, combining the filtrate, and performing reduced pressure distillation on the combined filtrate to obtain a light yellow transparent liquid;

[0041] Step S3, separating the light yellow transparent liquid obtained in step S2 by column chromatography, wherein the mobile phase of the column chromatography is: petroleum ether / ethyl acetate = 24 / 1, collecting the corresponding components, and performing reduced pressure distillation to obtain a light yellow liquid product (EPA-ME).

[0042] Experimental Example 1: Nuclear Magnetic Resonance Analysis of Eicosapentaenoic Acid Anisyl

[0043] 1. Experimental methods:

[0044] The eicosapentaenoic acid anisyl obtained in Example 1 was subjected to nuclear magnetic resonance (NMR) analysis.

[0045] 2. Experimental results:

[0046] The experimental results are as follows Figure 2 and Figure 3 shown.

[0047] Example 1 Eicosapentaenoic acid anisyl ester (EPA-ME) 1 H NMR spectrum (with CDCl3 as solvent) Figure 2 As shown; Example 1 prepared eicosapentaenoic acid anise ester (EPA-ME) 13 C NMR spectrum (with CDCl3 as solvent) Figure 3 shown.

[0048] Specifically:

[0049] (1) Eicosapentaenoic acid anisyl ester obtained in Example 1 1 The H spectrum is: 1H NMR(500MHz,Chloroform-d)δ7.31-7.27(m,2H,H-3,H-7),6.91-6.86(m,2H,H- 4,H-6),5.45-5.26(m,10H,-CH=CH-),5.05(s,2H,H-1),3.81(s,3H,-O-CH3),2 .87-2.76(m,8H,-CH=CH-CH2-CH=CH-),2.34(t,J=7.5Hz,2H,H-2'),2.13-2.02 (m,4H,H-4',H-19'),1.73-1.68(m,2H,H-3'),0.97(t,J=7.5Hz,3H,-CH2CH3).

[0050] (2) Eicosapentaenoic acid anisyl obtained in Example 1 13 The C spectrum is: 13 C NMR(126MHz,Chloroform-d)δ173.15(C1'),159.62(C4),132.05(C18'),130.08(C3),128.9 7(C8'),128.84(C9'),128.58(C11'),128.27(C12'),128.25(C14'),128.13(C17'),127.90( C5'),127.04(C6'),113.95(C3),65.97(C1),55.29(C8),33.75(C2'),26.56(C16'),25.64(C 13'),25.61(C10'),25.56(C7'),24.79(C3'),20.57(C19'),14.29(C20').MS(ESI,+ve):m / z 445.1[M+Na + ].

[0051] Experimental Example 2: Effect of Eicosapentaenoic Acid Anisyl on Hyperlipidemia

[0052] 1. Experimental materials:

[0053] Eicosapentaenoic acid anisyl ester (EPA-ME) prepared in Example 1, simvastatin (commercially available product).

[0054] 2. Experimental methods:

[0055] Fifty healthy male SD rats were selected and randomly divided into 5 groups, 10 in each group, which were recorded as normal control group, high-fat model group, simvastatin group, EPA-ME group and simvastatin + EPA-ME group. During the experiment, each group was treated with simvastatin, EPA-ME alone and simvastatin + EPA-ME combined treatment intervention on the basis of low-fat diet D12450 and high-fat diet D12451 as shown in Table 1. The animals were routinely raised and had free access to food and water. The experimental period was 4 weeks. After 4 weeks, the tail was cut off in the morning to collect blood, and the contents of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in serum were detected using an automatic biochemical analyzer. At the same time, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver were determined by TBA method and hydroxylamine method, respectively, and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were determined by automatic biochemical analyzer. Baseline tests were performed on each group of experimental animals before treatment to ensure the accuracy and reliability of the experiment. At the end of the experiment, the changes in body weight were recorded.

[0056] Table 1 Grouping of SD rats and intervention of diet and drugs before and after modeling

[0057]

[0058]

[0059] Note: High-fat diet D12451 and low-fat diet D12450 are derived from Research Diets.

[0060] 3. Experimental results:

[0061] 3.1. Results of weight changes in SD rats:

[0062] The weight of rats is an important physiological index, which reflects the health status of animals and the influencing factors during the experiment. The weight change results of SD rats are shown in Table 2 and Figure 4-5 As shown:

[0063] Table 2 Body weight changes of SD rats after drug treatment

[0064] Control group 27.67±11.17 High fat model group 39.77±15.48 Simvastatin group 29.23±11.20 EPA-ME group 29.69±13.45 Simvastatin + EPA-ME group 24.57±13.07

[0065] From Table 2 and Figure 4-5It can be seen that the average weight gain of rats in the high-fat model group was about 50% higher than that of normal rats after high-fat diet modeling, and the weight increased significantly. This shows that rats with high-fat diet are more likely to develop obesity symptoms. At the same time, the high-fat diet was successfully used to obtain a rat hyperlipidemia model.

[0066] When rats with hyperlipidemia were treated with simvastatin, EPA-ME, and simvastatin + EPA-ME, the weight gain rate of the rats returned to a level close to normal. Among them, the use of simvastatin and EPA-ME alone had similar effects on the weight control of rats, and both restored the weight of rats from 50% higher than that of normal rats to a level equivalent to that of normal rats. In addition, when rats with hyperlipidemia were treated with simvastatin + EPA-ME, the weight gain of the rats was the lowest, about 90% of the control group. This preliminarily shows that EPA-ME has a similar effect as simvastatin in reducing the risk of obesity.

[0067] 3.2. Detection results of TG, TC, LDL-C and HDL-C in SD rat serum:

[0068] Increased levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in the blood are major risk factors for cardiovascular disease and are closely related to atherosclerosis and cardiovascular events. High-density lipoprotein cholesterol (HDL-C) helps to remove cholesterol deposits in blood vessels and is considered to have a protective effect on cardiovascular health. Therefore, the four blood lipids in serum are often used to evaluate the effects of lipid-lowering drugs. After the experiment, the levels of TG, TC, LDL-C, and HDL-C in the serum of each group of rats are shown in Tables 3 and Figure 6 shown.

[0069] Table 3 The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the serum of rats in different drug groups

[0070]

[0071] From Table 3 and Figure 6It can be seen that the TC, TG and LDL-C levels of rats in the hyperlipidemia model all increased significantly, and their contents were 2 times or more than those in normal rats, while the HDL-C level was lower than that of normal rats. After the intervention of simvastatin, EPA-ME and simvastatin + EPA-ME combined treatment, the TC, TG and LDL-C levels of hyperlipidemia rats decreased to varying degrees. Among them, the effects of simvastatin and EPA-ME were similar. After the intervention of the two, the TC, TG and LDL-C levels in rats were reduced to the same level as the control group. In addition, the combination of simvastatin and EPA-ME can further reduce the TC, TG and LDL-C levels in the body to a certain extent. At the same time, after the intervention of the above three groups of drugs, the HDL-C content in rats increased to about 40% higher than that of normal rats. This shows that EPA-ME has a very significant lipid-lowering effect, and its combination with simvastatin can further enhance the lipid-lowering effect.

[0072] 3.3. Test results of SOD, MDA, ALT and AST in SD rat serum:

[0073] The function of the liver in the body is vital, especially in the regulation of lipid metabolism. Imbalance in lipid metabolism may lead to abnormal accumulation of lipids such as triglycerides, and even induce fatty degeneration, which in turn leads to diseases such as fatty liver. Studies have reported that chemicals can achieve the effect of lowering blood lipids by scavenging free radicals in the body and inhibiting lipid peroxides. Superoxide dismutase (SOD) is one of the main antioxidant enzymes in cells. Its main function is to scavenge superoxide anion free radicals and protect cells from oxidative damage. When liver lipid metabolism is disordered, SOD activity may be affected, leading to an aggravation of the oxidative stress state. In this case, the lipid peroxidation product MDA in the cell increases. At the same time, abnormal liver lipid metabolism may also cause damage to the cell membrane, releasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the cytoplasm. Therefore, the lipid-lowering effect of the drug can be evaluated by detecting relevant indicators. The experimental results are shown in Tables 4 and Figure 7 shown.

[0074] Table 4 Changes of SOD, MDA, ALT and AST levels in serum of rats in different drug groups

[0075]

[0076] From Table 4 and Figure 7It can be seen that the SOD content in the serum of high-fat model rats is about 50% lower than that of the control group, and the MDA is about 200% higher than that of the control group. The decrease in SOD enzyme activity in the serum of rats on a high-fat diet indicates that the body's antioxidant capacity is reduced and the accumulation of free radicals is increased, thereby increasing the degree of oxidative stress. This may cause cell damage, inflammatory response and tissue damage, and may also aggravate the development of oxidative stress and cardiovascular disease. MDA (malondialdehyde) is a lipid peroxidation product and is generally regarded as a marker of cellular oxidative damage. The increase in MDA is generally regarded as an indicator of increased oxidative stress levels and cell damage, and is closely related to the occurrence and development of various diseases including cardiovascular disease. After intervention with simvastatin, EPA-ME and simvastatin + EPA-ME combined treatment, the SOD content in rats gradually increased, from about 50% lower than the control group to about 15% higher than the control group, and the SOD enzyme activity in the body was significantly enhanced. At the same time, after the intervention of the three groups of drugs, the MDA content in the rats gradually decreased, among which the combined treatment of simvastatin + EPA-ME can reduce the MDA content to the maximum extent. At this time, the MDA content in the rats decreased from about 200% higher than the control group to almost the same as the control group. This shows that EPA-ME has the effect of significantly increasing the SOD content and reducing the MDA content. In addition, the combination of simvastatin and EPA-ME can maximize the effect of reducing the MDA content.

[0077] ALT (alanine aminotransferase) and AST (aspartate aminotransferase) are two common liver function indicators, which exist in liver cells. Under normal circumstances, the content of ALT and AST is low. When the liver is damaged, such as when the body is in a state of hyperlipidemia, lipids accumulate excessively in the liver, causing damage to liver cells, which in turn causes cell membrane rupture, and ALT and AST are released into the blood. Therefore, the liver status can be evaluated by detecting the content of ALT and AST. Figure 7 It can be seen that the ALT and AST levels in hyperlipidemic rats were significantly higher than those in the control group, and were about 200% and 30% higher than those in normal rats, respectively. After intervention with simvastatin, EPA-ME, and simvastatin + EPA-ME, the ALT and AST levels gradually decreased. Among them, the combined treatment of simvastatin and EPA-ME had the best effect. The combination of the two could reduce the ALT and AST levels to the same level as normal rats, which was further reduced by about 20% compared with the intervention of simvastatin alone.

[0078] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by a person of ordinary skill in the art without departing from the spirit and technical concept disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. A method for preparing eicosapentaenoic acid anisyl ester, characterized in that: The following steps are involved: Step S1, adding 4-methoxybenzyl alcohol and eicosapentaenoic acid into a round-bottom flask containing tetrahydrofuran solution, stirring at room temperature for 4-6 min, then adding lipase into the system, stirring and reacting at 28-35° C. for 7-9 h, filtering and taking a filter cake; Step S2, washing the filter cake obtained in step S1 with petroleum ether for 3 to 4 times, collecting the filtrate, combining the filtrate, and performing reduced pressure distillation on the combined filtrate to obtain a light yellow transparent liquid; Step S3, separating the light yellow transparent liquid obtained in step S2 by column chromatography, collecting corresponding components, and performing reduced pressure distillation to obtain a light yellow liquid product; The eicosapentaenoic acid is all-cis-5,8,11,14,17-eicosapentaenoic acid.

2. The method for preparing eicosapentaenoic acid anisyl according to claim 1, wherein: The molar ratio of 4-methoxybenzyl alcohol to eicosapentaenoic acid in step S1 is 36.2 mmol / L:39.7 mmol / L.

3. The method for preparing eicosapentaenoic acid anisyl according to claim 1, wherein: In the step S1, the material-liquid ratio of 4-methoxybenzyl alcohol to tetrahydrofuran solution is 1 g: (8-12) mL.

4. The method for preparing eicosapentaenoic acid anisyl according to claim 1, wherein: In step S1, the weight ratio of eicosapentaenoic acid to lipase is 4:(1-2).

5. The method for preparing eicosapentaenoic acid anisyl according to claim 1, characterized in that: The lipase in step S1 is Novozym 435 enzyme.

6. The method for preparing eicosapentaenoic acid anisyl according to claim 1, characterized in that: During the reaction process of step S1, thin layer chromatography was used to monitor the reaction, and the developing solvent of the thin layer chromatography was: petroleum ether / ethyl acetate = 9 / 1, Rf = 0.

6.

7. The method for preparing eicosapentaenoic acid anisyl according to claim 1, characterized in that: The mobile phase of the column chromatography in step S3 is: petroleum ether / ethyl acetate=24 / 1.

8. Eicosapentaenoic acid anisyl obtained by the preparation method of eicosapentaenoic acid anisyl according to any one of claims 1 to 7.

9. Use of eicosapentaenoic acid anisyl obtained by the preparation method of eicosapentaenoic acid anisyl according to any one of claims 1 to 7 or eicosapentaenoic acid anisyl according to claim 8 in the preparation of a drug for preventing or treating hypolipidemics.

10. Use of eicosapentaenoic acid anisyl obtained by the preparation method of eicosapentaenoic acid anisyl according to any one of claims 1 to 7 or eicosapentaenoic acid anisyl according to claim 8 in the preparation of a drug for preventing or treating hyperlipidemia.

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