JPS5967245A - Method for concentrating and separating highly unsaturated fatty acid ester - Google Patents

Abstract

PURPOSE:To concentrate and separate the titled compound, by adsorbing an ester of a fatty acid having a high unsaturation selectively from a fatty acid ester mixture on a synthetic zeolite, and desorbing the fatty acid ester selectively with a polar solvent. CONSTITUTION:A fatty acid ester mixture containing a highly unsaturated fatty acid ester (hereinafter abbreviated to EPA) is dissolved in a nonpolar solvent, e.g. n-hexane, and brought into contact with a synthetic zeolite 5-13Angstrom average inside pore diameter to adsorb the EPA thereon. The synthetic zeolite layer and the nonpolar solvent layers are fractionated to remove the fatty acid ester having a low unsaturation degree. A polar solvent, e.g. acetone, is then brought into contact with the synthetic zeolite layer to desorb the EPA, and the polar solvent is removed from the resultant polar solvent layer to concentrate and separate the EPA. The above-mentioned synthetic zeolite is capable of adsorbing the EPA selectively in the interior of pores, and the resultant EPA has a high purity without causing coloring due to no polymerizing nor isomerizing.

Description

Detailed Description of the Invention The present invention utilizes the difference in affinity of synthetic zeolite with various fatty acid esters to selectively synthesize unsaturated zeolites containing highly unsaturated fatty acid esters (abbreviated as EPA in the following description). The present invention relates to a method for concentrating and separating j) EPA by adsorbing fatty acid esters with high properties onto synthetic zeolite and then selectively desorbing them using a polar solvent.

In the present invention, EPA is a general term for eicosabentaenoic acid ester (C20:5) and docosahexaenoic acid ester (C22:6).

Conventionally, 11 pA contained in animal and vegetable oils, especially fish oil, has been added and used in the form of compound feeds mainly as an essential lipid for fish fillets, but the physiological activity of EPA and its pharmacological effects on humans have been elucidated. Now that its usefulness has been confirmed, it has become necessary to develop a method for industrially producing EPA with high purity.

Methods for concentrating and separating EPA'i from a fatty acid ester mixture include 1) molecular distillation, 2) urea addition, 3) thin layer chromatography, 4) gas chromatography, and 5) high performance liquid chromatography. However, method 1) is prone to isomerization and polymerization, resulting in a decrease in quality.
The purity limit of EPA is also about 40%. Method 2) requires a large amount of urea and a solvent such as methanol, and has a purity limit of 50%. 3)% 4), 5)
Although the method described above yields highly pure EPA, it is originally an analytical method and is therefore disadvantageous for obtaining EPA on an industrial scale.

As a result of intensive research into a method for industrially supplying high-purity EP A f, the present inventors focused on the characteristics of synthetic zeolite and invented this method.

That is, the present invention provides a method for concentrating and separating EPA, which is characterized by carrying out the following steps a) to d).

a) A step of dissolving a fatty acid ester mixture containing gpA in a non-polar solvent and contacting it with a synthetic zeolite having an average pore diameter of 5 to 13 A to adsorb the highly unsaturated fatty acid ester, b) A step of dissolving the fatty acid ester mixture containing gpA in a non-polar solvent, and b) combining the synthetic zeolite layer with the non-polar one. C) A step of separating the fatty acid esters from the synthetic zeolite layer and removing the less unsaturated fatty acid esters together with the nonpolar solvent; d) removing the polar solvent from the obtained polar solvent layer.

The fatty acid ester used in the method of the present invention is an ester obtained from a fat extract containing EPA and a lower alcohol such as methanol, ethanol, propatool, butanol, etc. It is an ester of

In addition, fatty acid esters of polyhydric alcohols such as glycol and glycerin can also be used.

Specific examples include methyl or ethyl esters of fatty acids obtained by transesterifying marine animal oils such as fish oil and cod liver oil, as well as various complementary animal and vegetable oils, with methanol or ethanol in the presence of a catalyst. Furthermore, fish oil and liver oil can also be used.

In the present invention, the nonpolar solvent includes n-hexane,
Cyclohexane, n-pentane, cyclopentane, n-
A wide range of linear, cyclic, or cyclic nonpolar solvents such as octane, benzene, xylene, and ether can be used. A mixed solvent of two or more of these can also be used.

The synthetic zeolite used as an adsorbent in the present invention preferably has an average internal pore diameter in the range of 5 to 13 A, particularly 8 to I
I like the OA one.

Synthetic zeolite with an average internal pore diameter of 5 to 13A selectively adsorbs highly unsaturated fatty acid esters into its internal pores, and hardly adsorbs saturated and monoene fatty acid esters. If the average pore diameter is smaller than this range, the adsorptivity will be poor, and if it is larger than this range, the selectivity will be poor, so it is not preferable.

A wide range of polar solvents can be used in the present invention, such as acetone, methyl ethyl ketone, methanol, ethanol, propatool, and chloroform. A mixed solvent of two or more of these can also be used. When a synthetic zeolite that has adsorbed highly unsaturated fatty acid esters is brought into contact with this polar solvent, the fatty acid esters are selectively desorbed and dissolved in the solvent depending on the amount of solvent used.

The treatment temperature is the process of dissolving the fatty acid ester in a non-polar solvent and bringing it into contact with synthetic zeolite, and the process of bringing the zeolite into contact with a polar solvent to desorb the highly unsaturated fatty acid ester. This is possible within the temperature range commonly used (20 to 70°C). The lower the temperature, the slower the adsorption and desorption, so it is better to heat it to some extent, but if the processing temperature is higher than the boiling point of the solvent used, a pressurizing device will be required and the cost will increase, so the temperature should be 35 to 55℃. A range of is particularly preferred.

The method of carrying out the present invention is to first esterify a fat or oil containing EPA with a lower alcohol using a catalyst in a conventional manner, and then dissolve this ester in a non-polar solvent of 10 to 100 times the weight of 6-6. do.

Next, add 1 of the above synthetic zeolite to this solution.
After adding ~10 times the weight and stirring for ~3 hours, the solution is passed from door to door or through a zeolite layer that has been prepared in advance. If the pressure loss is large when the liquid is passed through the zeolite layer, a filter aid may be mixed with the zeolite.

Through the above steps, most of the unsaturated small fatty acid esters such as spores and monoenes are removed while being dissolved in the nonpolar solvent.

Next, a polar solvent with an amount of 2 to 100 N times that of the zeolite was added to the synthetic zeolite that had adsorbed the highly unsaturated fatty acid ester, and the mixture was stirred for 3 to 2 hours, and the process of separating the mixture was repeated 1 to 5 times, or the mixture was shredded. 10 in the zeolite layer
By passing ~100 times the polar solvent and dividing the outflowing solution into 2 to 50 fractions, fatty acid esters with weak affinity for zeolite can be sequentially desorbed, and at the same time they can be separated.

The purity of EPA improves as the amount of polar solvent added to the synthetic zeolite is reduced and the steps of pouring, stirring, and door-to-door repeating are repeated. Also, when passing a polar solvent through the zeolite layer, it is better to divide the flowing solution into smaller pieces! 1P A with improved purity is obtained. Conditions may be selected from the above range depending on the intended use of the EPA.

The affinity between synthetic zeolite and fatty acid ester is most influenced by unsaturation, but the number of carbon atoms in the fatty acid ester and its structure are also considered to be factors, depending on the order of desorption.

Then the EPAal in the solution divided using the above process
By subjecting the high i fraction to simple distillation, highly pure EPA separated from the bath agent can be obtained. The polar solvent distilled by simple distillation can be reused, and the other fractions can also be separated into fatty acid ester and solvent by simple distillation, and the fatty acid ester can be used for other purposes, and the solvent can be reused.

The synthetic zeolite can be used repeatedly by washing it with a nonpolar solvent after the separation.

As described above, the EPA obtained by ICl has high purity and 1
Since neither polymerization nor isomerization occurs, there is almost no coloration.

Next, the present invention will be explained by examples. All fatty acid compositions were determined by gas chromatography. Shito t6
)-/, 11 奎117. -1. Fake.

Example 1 Fatty acid methyl ester was obtained by reacting small fish oil such as sardine and mackerel with methanol using sodium methylate as a catalyst. The fatty acid composition of this raw material is shown in Table 1 (C2o: 5-14
1%, C'=7.9%).

5000 I of n-hexane to mg of this fatty acid methyl! 200 t of synthetic zeolite with an average internal pore diameter of 9 A was added to this solution, and after stirring slowly at room temperature for 2 hours,
We went door to door. Next, 400% of chloroform was added to this zeolite.
After adding 0# and slowly stirring at room temperature for T1 hour, the mixture was delivered to each door. 9- Distill the solvent off the liquid and extract the fatty acid methyl ester15.
31! I got f. Its fatty acid composition is shown in Table 1 (C2o.

5=65.3%, C2°, 6=17.5%). It can be seen from the results in Table 1 that the purity of EPA was significantly improved.

Comparative Example-1 Using synthetic zeolite with an average internal pore diameter of 4A instead of the synthetic zeolite with an average internal pore diameter of 9A in Example-1, Example-
It was done in exactly the same way as 1. As a result, only 1.7 g L of fatty acid methyl ester was obtained, and the fatty acid composition was as shown in Table 1 (C2o, 5-234%).

C2□, 6-112%).

It can be seen that both the purity and yield of EPA are significantly inferior to Example-1.

Example-2 5oooy' of benzene was added to 100f of fatty acid ethyl ester obtained by reacting the same small fish oil as in Example-1 with ethanol.
Synthetic zeolite 1009 having an average internal pore diameter of 12A was added to this solution, stirred slowly at room temperature for 1 hour, and then separated. The rest is as follows (Real-I 〇- 5-678%, C=16.8%)22
: 6.

Example 3 4000JFk of n-hexane was added to 00t of the fatty acid ethyl ester of Example 2 to dissolve it, 20Off of synthetic zeolite with an average internal pore diameter of 9A was added to this solution, and the mixture was heated at 50℃ for 30
After stirring slowly for several minutes, the mixture was separated. Next, 500 f' of chloroform was added to this zeolite, and the mixture was slowly stirred at 40° C. for 30 minutes and then separated. Further, 3000 f of chloroform was added to this zeolite, and the mixture was slowly stirred at 40° C. for 1 hour and then separated. The solvent was distilled off from this P solution to obtain 146 tons of fatty acid ethyl ester. The fatty acid composition was as shown in Table 1 (C=79.3%, C2□, 6=20:520.5%).

Example-4 100 tons of fatty acid methyl ester of Example-1 was mixed with 4000 tons of hexane/ether 5o15o (li ratio) mixed solvent.
This solution was combined with Example 1, 5-638%, C
2□, 6=14.6%).

Example-5 Fatty acid ethyl ester of Example-2 100? was dissolved in 5,000 # of hexane, 200 f of synthetic zeolite with an average internal pore diameter of 6 mm was added to this solution, and after stirring slowly at 40° C. for 1 hour, it was separated. Next, 6000 f'f of ethanol was added to this zeolite, and the mixture was slowly stirred at 40° C. for 1 hour and then separated. The solvent of this Pi was distilled off to obtain fatty acid ethyl ester 12.6#. The fatty acid composition was 22:6 as shown in Table t (C20, s-712%, C=17.4%).

Sun 50001? 200 tons of synthetic zeolite having an average internal pore diameter of 9A was added to the solution prepared by adding and dissolving -, and after stirring slowly at 40°C for 2 hours, P was separated. Next, 4000p of chloroform was added to this zeolite and reacted with methanol. As a result of gas chromad analysis of fatty acid methyl ester, the fatty acid composition was found in Table 1 (C2o, 5=
26.5%, C22:6= triglyceride,
There are almost no triglycerides in which two molecules of EPA are bound as fatty acids, and even if only triglycerides containing EPA'i can be selectively separated by 100%, theoretically, EPA accounts for only about 35% of the fatty acid composition. Therefore, it can be seen that the method of Example 6 achieves remarkable concentration and separation of gPA.

Comparative Example 2 A synthetic zeolite having an average internal pore diameter of 4A was used in place of the synthetic zeolite having an average internal pore diameter of 9A in Example 6, and the same method as in Example 6 was carried out. Methyl esterification was performed using the same method, and the fatty acid composition was analyzed, as shown in Table 1 (C2o, 5=16.2%, C22:6=s
, 6%), almost no improvement in the purity of EPA was observed.

Example-7 20 of fatty acid ethyl ester 1011 of Example-2
After dissolving in n-hexane, the solution was passed through a cylinder with an inner diameter of 3.5 elI and a depth of 30α equipped with a glass filter filled with a well-mixed mixture of 30 g of synthetic zeolite with an average inner pore diameter of 10 cA and 3 Of diatomaceous earth.

At this time, the column was kept warm at 50° C., and the liquid flow rate was 1 d/min. Subsequently, chloroform 500117 was passed through at a rate of 1 M 1 Z, and the effluent was divided into fractions of 50 ml each. As a result of distilling off the solvent from each fraction, fatty acid ethyl esters shown in Table 2 were obtained. The total yield of fractions 4G, 7, and 8 is 1.43 #, and the purity of the C20:5 component is 811%.
The yield was 14-823%.

By dividing into fractions in this way, C2o,
It is possible to selectively concentrate and separate only 5.

As is clear from the above Examples 1 to 7, the method of the present invention is extremely excellent as a method for concentrating and separating EPA.

Claims (1)

[Scope of Claims] A method for concentrating and separating highly unsaturated fatty acid esters, which comprises carrying out the following steps a) to d). a) A fatty acid ester mixture containing a highly unsaturated fatty acid ester is dissolved in a non-polar solvent, and the average internal pore diameter is 5 to 13.
A step of adsorbing the highly unsaturated fatty acid ester by contacting the synthetic zeolite with a reed; b) separating the synthetic zeolite layer and the non-polar solvent layer to remove the less unsaturated fatty acid ester along with the non-polar solvent; Step C) A step of bringing a polar solvent into contact with the synthetic zeolite layer to desorb the highly unsaturated fatty acid ester from the synthetic zeolite layer; d) A step of removing the polar solvent from the obtained polar solvent layer.