JPH04503823A - Production method of fatty acid glyceride - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Production method of fatty acid glyceride The invention provides at least 40% by weight, especially at least 50% by weight of fatty acid residues. is a fatty acid having 18 to 22 carbon atoms and 3 or more olefinic double bonds , fatty acid glycerides, especially those derived from ω-3-fatty acids, At least 40% by weight, especially at least 50% by weight of the acid residues are at least Derived from fatty acids with three olefinic double bonds, especially ω-3-fatty acids Glycerol is a mixture of fatty acid methyl or ethyl esters. The reaction is carried out by heating in the presence of a basic catalyst in an inert gas atmosphere. It relates to a manufacturing method by carrying out the manufacturing process.

Fatty acids with 3 or more olefinic double bonds, i.e. 3 or more unsaturations fatty acids, especially fatty acid mixtures with a high content of so-called ω-3 fatty acids [Eico sapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (alkyl esters) esters and their derivatives such as glycerides), It has been used for the prevention of heart and circulatory system diseases since 2013.

Omega-3 fatty acids in the form of glycerides are naturally occurring in marine animal fats and oils, especially fish oils. It is a natural ingredient. However, the content of such fats and oils varies significantly depending on the raw material. very different. ω-3 = Even fish oil with a relatively high fatty acid content has such a content of 30% by weight or more. They rarely contain fatty acids. However, using fish oil prophylactically and concomitantly Higher ω-3-fatty acid content is required to avoid unnecessary administration of fat. It will be done. Various methods have been proposed to increase the fatty acid content in fish oil formulations. Ru. In other words, by gradually cooling (winterizing) fish oil, Increasing the concentration of ω-3-fatty acid glycerides in oil formulations can improve chemistry Cheii-stry and I industry, March 7, 1988, pages 139-145, which states that in fish oil Convert the glycerides present into fatty acids or fatty acid esters and then desirably It is also described that the missing components are removed with urea or distilled. Similar person A method is described in US Pat. No. 4,377,526.

The method includes a solvent, possibly a readily flammable solvent, as well as additional reagents. It involves the use of. Furthermore, the final products of such methods are It is expensive. Moreover, the final product of the process is free ω-3-fatty acids or Because it contains an alkyl ester of It's not the same thing.

Therefore, the concentrate of ω-3-fatty acid or its ester obtained by the above method There have been numerous attempts to produce them in a simpler way and convert them back to glycerides. It has been. In other words, Novo Industri iA/S, Denmark) publication BioTimes (BioTime) s), September 1988 issue, pages 2-3, Conversion to ceride is described.

However, such enzymatic transesterification of ethyl esters with fish oil is sufficient to produce stellate-free ω-3-fatty acid glycerides on an industrial scale. It's not something I can afford. Furthermore, in Japanese Patent Application Publication No. 62153249, Again, transesterification with fat, using sodium methylate as a catalyst. A method for preparing EPA glycerides from the corresponding ethyl esters by carrying out It is listed. However, ω-3 = fatty acids have a large number of double bonds, so they have an alkaline feel. Relatively high receptivity. When using sodium methylate as a catalyst, relatively high Double bond isomerization observed at low temperatures leads to loss of useful ω-3-fatty acids.

In addition, sodium methylate and the soap produced by it were subjected to transesterification. Therefore, it is troublesome to remove it from the resulting glyceride mixture. ethyl ester High concentrations of omega-3 fatty acid glycerol, such as when transesterifying with free glycerol, Obtaining lycerides by said method is not easily possible.

West German Published Patent No. 3716950 discloses the presence of anhydrous sodium carbonate as a catalyst. Below, triglyceride is produced by transesterifying fatty acid esters with glycerol. The method for producing lido is described. Carbonic acid, especially in the form of a solution in glycerol Sodium is also a fairly strong base, but surprisingly it is The reaction between acid ester and glycerol is the isomerization of double bonds present in fatty acids. I found it to be suitable for doing it without causing too much trouble. Furthermore, in this case is very easy to remove the catalyst after transesterification.

Therefore, the present invention relates to the method described at the beginning, in which carbonic anhydride is used as a basic catalyst). - Concerning how to use Rium. The glycerol used in the transesterification reaction is , acts as a solvent and as a reactant.

The starting compounds of the process of the invention, i.e., in the form of methyl or ethyl esters, At least 40% by weight, based on the total amount of fatty acids combined, at least 50% by weight C+5-tJ) with a weight % of 3 or more unsaturations is a fatty acid, especially an ω-3-fatty acid. methyl or ethyl ester mixtures are unsaturated, bound in the form of glycerides. It is best obtained from fish oils that have a relatively high content of fatty acids of number 3 or higher. For example, Journal of American Oil Chemists Society (J, A, O, C .

S), Vol. 40, 197-198 (1962) or U.S. Pat. No. 4,377,526 Such fish oils may be treated with sodium methylate or methanol or ethanol at its boiling point using tyrate as a catalyst. first converted to methyl or ethyl esters by reaction with alcohol or ethanol do. After washing away the catalyst, the ω-3-fatty acid esters are concentrated by distillation. do. The concentrated product obtained is the starting material for the process of the invention. But others omega-3-fatty acid methyl or ethyl esters concentrated by a method such as Of course, it is also possible to use one obtained by concentrating with urea. The ethyl Preference is given to using esters as starting materials.

Fatty acid residues of the starting materials and final products of the process of the invention, which are olefinic derived from fatty acids with three or more double bonds or from ω-3-fatty acids. What is not, is essentially fish oil, such as herring pond, sardine oil and menhade oil. of saturated and/or unsaturated Cl2-so fatty acids occurring as a natural component of green oil. It is a residue.

In a preferred embodiment of the method of the present invention, the method has three or more olefinic double bonds. The molar ratio of methyl or ethyl ester of fatty acid to glycerol is 3.1. 45.1, in particular 3.2:I to 35 l, is used in the transesterification reaction . The transesterification reaction is carried out at temperatures ranging from 150 to 200 °C, especially from 170 to 1 Preferably, it is carried out at a temperature in the range of 906C. Methyl or ethyla released The alcohol is extracted continuously from the reaction mixture by distillation, especially under slightly reduced pressure. Remove.

Any excess methyl or ethyl ester that may need to be added is added as the reaction progresses. and introduce it. To stop the reaction, increase the vacuum to about 10 hPa, for example. can be advantageous. Recycle the isomerization by not exceeding the reaction temperature of up to 200°C. must be avoided.

In another advantageous embodiment of the invention, the esterification product obtained according to the invention is It is purified by filtering out the sodium carbonate that is insoluble in the triglycerides.

It is also advantageous to add up to 5% by weight of bleaching earth to the reaction mixture before filtration. obtain. After filtration, excess methyl or ethyl ester is removed under high vacuum (e.g. 0.0 01-5 hPa) at a temperature of up to about 200 °C, preferably in a thin-layer evaporator, in a short path. Distill under distillation conditions.

The method of the invention is illustrated by the following examples.

A. Preparation of starting compounds The starting material is hand-produced, unwinclized Chilean fish oil, i.e. It is a fish oil that has not been pre-purified by slow cooling, and the analytical data is as follows. : Acid value 0.6 Saponification value 189.1 Iodine value: 194.5 Fatty acid composition (wt%, methyl ester) in fish oil determined by gas chromatography (in terms of tel) were as follows (only the most important components are shown; fatty acids and their carbon It is characterized by the number of elementary atoms m and the number of double bonds n (Cm:n)).

C, 4:8 7.0 Total ω-3-fatty acids (*): 35.9% by weight E P A -1-D HA Total: 31. O wt% Lovibond color value, 5 1/4” cell: Yellow 70, red 1000g of the above fish oil, 1500g of absolute ethanol and 20% The mixture was refluxed for 30 minutes with 90 g of sodium ethylate ethanol solution.

Then, 1200 g of ethanol was distilled off. The remaining product solution was diluted with 10,100 ml of water. mixed with O. The upper oil phase was separated and washed twice with 500 ml of water. Then, The oil phase was dried at 80°C under water jet vacuum (yield: 955 g), at a high vacuum of about 0.1 hPa. Distilled below. Boiling point of the product, designated Distillate I: 112-199°C.

yield: Distillate 1: 937g (98%) Residue I: 17g (2%) The thus prepurified transesterification product (distillate I) is then processed into a ceramic Fractionation was carried out under high vacuum in a column with a length of 40 cI11 containing a saddle. acid residue chain Relatively short chain ethyl esters up to long C+s (distillate); boiling point 102-161 'C/approx. 0.1 hPa; 494 g (53%)) was almost distilled off.

The residue ff (4.38 g, 47%) remaining in the flask was then converted into distillate ■. Boiling point 160-196°C/approx. 0.1 hPa; 424 g, 97%. centre 10.3 g (2.4%) remained in the flask: Residue ■.

From gas chromatographic analysis of the fatty acid composition (wt%) of distillates H and ■ As such, highly unsaturated fatty acids were highly concentrated in the distillate■: Distillate■ Distillate■ Total of ω = -3-fatty acids (*) in distillate In: 686% by weight E in distillate ■ Total of P A + D HA: 63.3% by weight.

Distillate ■ had the following characteristic data.

Acid value 0.2 Saponification value 165 Iodine value: 319° The theoretical yield of EPA+DHA in distillate m was more than 80%.

Wari Arashi The above distillate (In2In20O, 6 mol) was added to the dropping funnel, thermometer, distillation bridge and and a 500 ml flask equipped with a nitrogen introduction vibrator, and incubate for 2 hours in a nitrogen atmosphere. It was heated to 180° C. under a reduced pressure of 50 hPa. Then dried with calcium oxide Dissolve 0.9 g of sodium carbonate in 18 g (0.2 mol) of glycerol. , was added dropwise over 1 hour. Ethanol distillation begins after about 10 minutes, and the ethanol The water was collected in a water-cooled receiver. Half an hour after adding glycerol/sodium carbonate After that, 11120 g (0.06 mol) of distillate in 10% excess form were added over 1 hour. was added dropwise to complete the glycerol reaction. After another hour, reduce the pressure to 1.0 hP. Adjusted to a. The temperature was then held at 180°C for 1.5 hours.

After cooling the product was stirred for 15 minutes at 60°C with 1% bleaching earth, then sulfuric acid Filtered through a suction funnel with a thin layer of sodium applied.

The yield was 202g. Excess distillate product or unreacted ethyl ester (total 38 g) at 190°C under short-path distillation conditions in a thin-layer evaporator. Distilled under reduced pressure of hPa. The residue from the thin layer evaporator was treated with 1% bleaching earth at 60% Treated again for 15 minutes at °C and filtered. Glyceride concentrate with the following analytical data 162g was obtained; Acid value 0.5 Saponification value 170 Iodine value 293 Sodium content 35ppI11 Glycerol below detection limit Glyceride distribution by Iatroscan analysis l): Noglyceride 1% Diglyceride 11% Triglyceride 88% Lovibond color, 5 l/4" cell: yellow 30, red 70I) Journal of Chromatography (J, of Chromato-graphy) 205 (1981), 331-347° Gas chroma of ω-3-fatty acids in reaction products Tographic analysis showed the following distribution (weight%, methyl ester equivalent) 2018:4 1, I C2o, 526.3 (EPA) C22:54.7 C2□:6 33.4 (DHA) Total ω-3-fatty acids + 65.6% by weight Total EPA + DHA: 59.7% by weight Conversion rate was approximately 85%. The product showed good low temperature stability for a long time at 16℃. Even after standing for a while, only a very small amount of crystals separated.

All of the above reactions to produce starting materials and final products are carried out under inert gas. The test was carried out in an atmosphere (nitrogen).

international search report international search report EP 9000285 S^　34997

Claims (4)

[Claims] 1. At least 40% by weight, especially at least 50% by weight of the fatty acid residues are carbon Fatty acids having 18 to 22 elementary atoms and 3 or more olefinic double bonds, In particular, fatty acid glycerides derived from ω-3-fatty acids are converted into fatty acid residues. at least 40% by weight, especially at least 50% by weight of at least 3 derived from fatty acids with olefinic double bonds, especially ω-3-fatty acids A mixture of fatty acid methyl or ethyl esters is esterified with glycerol. The reaction is carried out in an inert gas atmosphere in the presence of a basic catalyst without heating. This is a method of manufacturing by using anhydrous sodium carbonate as a basic catalyst. A method characterized by using um. 2. In the transesterification reaction, methyl or ethyl ester and glycerol using a molar ratio of 3:1 to 4.5:1, especially 3.2:1 to 3.5:1. The method according to claim 1, characterized in that: 3. The transesterification reaction is carried out at a temperature of 150-200°C, especially 170-190°C. 3. The method according to claim 1, wherein the method is carried out at a temperature of . 4. The products of the transesterification reaction are removed by filtration of the sodium carbonate and as required. and then purification by distillation of unreacted methyl or ethyl ester. A method according to at least one of claims 1 to 3.