JPH06240289A - Production of fatty acid ethyl ester mixture containing docosahexaenoic acid ethyl ester - Google Patents

Abstract

PURPOSE:To improve the efficiency of production by adding a specified amount of ethyl alcohol and a specified amount of sulfuric acid to a raw material containing docosahexaenoic acid, heating the mixture under reflux, distilling off the alcohol from the reaction mixture and removing the sulfuric acid from the residue. CONSTITUTION:To a reactor equipped with a reflux apparatus and an agitator, a stock oil containing docosahexaenoic acid acid (DHA), 0.8-1.2 pts.wt., per pt.wt. stock oil, ethyl alcohol of a purity of 95-99% and 0.08-0.11 pt.wt. sulfuric acid of a purity of 95-99 % are fed, and heated under reflux for 8-12hr. The ethyl alcohol is then distilled off from the reaction mixture, and the sulfuric acid is removed from the residue by washing with hot water at 70-95 deg.C to obtain a fatty acid ethyl ester mixture. This mixture is subjected to molecular distillation to obtain a concentrate of crude DHA ethyl ester. This concentrate is dissolved by the addition of a silver nitrate solution, toluene or the like is added to the obtained solution, and the resulting mixture is left at rest, the silver nitrate layer is removed from the mixture and the toluene is distilled off from the remaining layer to obtain a DHA ester of a purity of 95% or above.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for producing a fatty acid ethyl ester mixture containing DHA ethyl ester useful for producing docosahexaenoic acid (hereinafter abbreviated as DHA).

[0002]

BACKGROUND OF THE INVENTION Docosahexaenoic acid (DHA) is an omega-3 fatty acid contained in large amounts in fats and oils, especially in fish oils of certain fish, such as tuna and bonito head oil. . In recent years, it has been clarified that DHA is involved in various physiological actions, and thus has attracted attention in the medical field. For example, improvement of senile dementia such as vascular dementia and Alzheimer's disease due to activation of brain cells, restoration of visual acuity due to activation of eye cells, and further improvement of allergic symptoms such as pollinosis and asthma. Expected to work. By the way, in order to use DHA as a medicine or for research, it is necessary to stably supply high-purity DHA. The refined oil as a triglyceride obtained by the refining method of edible oil, which comprises deodorizing, deoxidizing and decolorizing crude oil, has a DHA content of only about 25% and cannot be used for the above purpose. This is because even if fish oil has a high content of DHA, one or two of the three fatty acid molecules contained in triglyceride are DHA, and the others are eicosapentaenoic acid (EPA), oleic acid, palmitic acid, stearic acid. , Other fatty acids such as linoleic acid.

Therefore, in order to obtain high-purity DHA from triglyceride fats and oils, the fats and oils are first hydrolyzed into fatty acids and glycerin, and then DHA is separated and purified from the hydrolysis mixture by molecular distillation or the like. .
In this case, the fatty acid form is difficult to separate and easily decomposes during the process, so the molecular weight of the ester derivative is changed to facilitate evaporation at a low boiling point and prevent changes due to oxidation etc. during the process. is doing. Therefore, separation and purification of DHA from crude oil (mainly fish oil) includes the following steps. 1) Crude oil containing DHA is washed with an acid and then hydrolyzed with alkali to decompose into fatty acid and glycerin. 2) A fatty acid is converted into an ester in the presence of alcohol and sulfuric acid to obtain an ester mixture. 3) Separation and purification of DHA ester from the ester mixture to obtain highly pure DHA ester. Since the above steps require time and labor for alkali hydrolysis and esterification, a more efficient and economical method has been desired.

[0004]

Means for Solving the Problems The present inventors have conducted diligent research to provide an efficient purification method for obtaining DHA, which is useful as a drug, at low cost, and as a result, under certain conditions. When processing crude oil containing DHA,
It has been found that it is possible to convert to a fatty acid ester mixture in one step, and the present invention has been completed. That is, the present invention provides 0.8 parts by weight of 1 part by weight of crude oil containing DHA.
1.2 parts by weight of ethyl alcohol and 0.08-0.11.
Provided is a method for producing a fatty acid ethyl ester mixture containing a DHA ethyl ester, which comprises mixing 1 part by weight of sulfuric acid, heating and refluxing for 8 to 12 hours, and then distilling off alcohol to remove sulfuric acid from the residue. It is a thing. The fatty acid ethyl ester mixture of the present invention is highly pure DHA.
It is useful for the production of esters. That is, the mixture is subjected to molecular distillation according to a conventional method to separate and concentrate DHA ethyl ester, and then purified by, for example, the silver nitrate method to obtain DHA ethyl ester having a purity of 95% or more. The crude oil used in the method of the present invention is not particularly limited as long as it contains a large amount of DHA. For example, fish oil obtained from the oil of the head of tuna or skipjack is suitable. The crude oil is preferably washed with a mixture of water and sulfuric acid in a conventional manner to remove proteins and gums.

Alcohols are arbitrarily selected, provided that when they form an ester with a fatty acid, the DHA ester can be easily separated from the ester of another fatty acid by molecular distillation. Lower alcohols are preferred,
Most preferred is ethyl alcohol. The purity of alcohol is preferably 95 to 99%, and particularly preferably 99%. Also, sulfuric acid has a purity of 95-
It is preferable to use 99%, particularly 99% pure. The mixing ratio of the three components is, for example, 0.8 to 1.2 parts by weight of ethyl alcohol, preferably 1 to 1 part by weight of crude oil.
1.2 parts by weight, more preferably 1 part by weight, sulfuric acid 0.0
The amount is 8 to 0.11 part by weight, preferably 0.1 to 0.11 part by weight, and more preferably 0.1 part by weight. These mixtures are heated and refluxed in a reaction kettle equipped with a reflux device and a stirrer. When using ethyl alcohol, the temperature at reflux is about 95 ° C. The reaction time is usually 8 to 12 hours, preferably 9 to 10 hours, most preferably about 10 hours. However, the heating time is not particularly limited and may be longer than that. Then the alcohol is distilled off,
The sulfuric acid is removed from the residual fatty acid ethyl ester mixture. Sulfuric acid can be easily removed by washing with warm water. The temperature of the warm water is 70 to 95 ° C, preferably 90 to 95 ° C, more preferably 95 ° C. According to the method of the present invention, about 95% or more of the fatty acids contained in crude oil are esterified and obtained as a mixture. When crude oil, ethyl alcohol, and sulfuric acid were 1: 0.7: 0.3, the yield was low at 55%. The fatty acid ethyl ester mixture of the present invention is then subjected to a molecular distillation machine to concentrate the DHA ethyl ester,
This can be purified by the silver nitrate method to obtain high-purity DHA ethyl ester. Hereinafter, the present invention will be described in more detail with reference to examples.

[0006]

Example 1 Crude oil containing DHA washed with sulfuric acid and water (ratio of fatty acid in crude oil; DHA: 25%, EPA: 6
%, Oleic acid: 17%, palmitic acid: 15%, stearic acid: 4%, linoleic acid: 2%) 600 kg, 600 kg of ethyl alcohol (purity 99%) and 60 kg of sulfuric acid (purity 99%) together with a stirrer and It is put in a reaction kettle equipped with a reflux device and heated under reflux at 95 ° C. for 10 hours.
The ethyl alcohol is then distilled and recovered. 1 residue
570 kg of fatty acid ethyl ester mixture is obtained by washing 5 times with 000 kg of warm water (95 ° C.). The mixture was a fatty acid ethyl ester mixture containing 95% of the fatty acids in the crude oil.

Reference Example 1 500 kg of the fatty acid ethyl ester mixture obtained in Example 1
Was placed in a molecular distillation machine and distilled at a vacuum degree of 0.008 mmHg and an internal temperature of 180 ° C. to remove the first fraction and the residual fraction, and to remove the main fraction to obtain a crude DHA ethyl ester concentrate (3
7%). Dissolve 100 L of the concentrate in 140 L of hexane and add to 153 L of silver nitrate solution with stirring,
The mixture is allowed to stand and separated, and the hexane layer is removed to obtain a silver nitrate solution containing DHA ethyl ester. To this silver nitrate solution, 4160 L of toluene was added and allowed to stand, and the silver nitrate layer was removed. Then, toluene is distilled off to obtain 24 L of DHA ethyl ester having a purity of 95% or more as a residue.

[0008]

According to the method of the present invention, a fatty acid ethyl ester mixture containing DHA ethyl ester can be obtained more efficiently than in the conventional method. From this mixture, DHA ethyl ester having a purity of 95% or more can be easily obtained. This DH
A-ethyl ester has an important physiological activity and is expected to be useful for treating various diseases and symptoms, and the method of the present invention can contribute to the development and promotion of research.

Claims (1)

[Claims] 1. 0.8 to 1.2 parts by weight of ethyl alcohol and 0.0 to 1 part by weight of crude oil containing docosahexaenoic acid.
Fatty acid ethyl ester mixture containing docosahexaenoic acid ethyl ester, which comprises mixing 8 to 0.11 parts by weight of sulfuric acid, heating and refluxing for 8 to 12 hours, distilling off alcohol, and removing sulfuric acid from the residue. Manufacturing method.