WO2020138282A1 - エイコサペンタエン酸アルキルエステル含有組成物及びその製造方法 - Google Patents
エイコサペンタエン酸アルキルエステル含有組成物及びその製造方法 Download PDFInfo
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- WO2020138282A1 WO2020138282A1 PCT/JP2019/051107 JP2019051107W WO2020138282A1 WO 2020138282 A1 WO2020138282 A1 WO 2020138282A1 JP 2019051107 W JP2019051107 W JP 2019051107W WO 2020138282 A1 WO2020138282 A1 WO 2020138282A1
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- alkyl ester
- acid alkyl
- epa
- area
- equosa
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- 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
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- 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
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C67/54—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
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- 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
- C07C67/58—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B3/00—Refining fats or fatty oils
- C11B3/12—Refining fats or fatty oils by distillation
Definitions
- the present invention relates to a composition containing an alkyl ester of eicosapentaenoic acid and a method for producing the same.
- PUFA Polyunsaturated fatty acid
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- the raw material for fats and oils of biological origin is a mixture of various fatty acids having different numbers of carbon atoms, number and position of double bonds, and composition ratio of stereoisomers, and the content of PUFA is not necessarily high.
- PUFA purified from a biologically-derived oil/fat raw material contains various trace impurities derived from the oil/fat raw material or produced by heat treatment in the refining process.
- impurities include, for example, unfavorable fatty acids such as arachidonic acid, saturated fatty acids, and PUFA trans isomers for cardiovascular events, and environmental pollutants such as environmental hormones and other substances that adversely affect the living body. obtain. Therefore, as a raw material for pharmaceuticals and health foods, there is a demand for a high-purity PUFA-containing composition that not only contains PUFA in a high concentration but also contains impurities that adversely affect the living body as low as possible.
- Patent Document 1 discloses environmental pollution including removal of environmental pollutants such as polychlorinated dibenzoparadioxin (PCDD) and polychlorinated dibenzofuran (PCDF) by thin film distillation from a feed oil containing PUFA as a constituent fatty acid.
- PCDD polychlorinated dibenzoparadioxin
- PCDF polychlorinated dibenzofuran
- Patent Document 2 an arachidonic acid ester and an EPA alkyl ester containing a EPA alkyl ester-containing composition, which is subjected to concentration distillation using chromatography after precision distillation at 0.2 Torr and 190° C. or lower.
- Patent Document 3 discloses that an oil composition is treated with an aqueous fluid and then subjected to a stripping treatment such as short-step distillation, so that an undesirable component in the oil composition, for example, a hydrophilic component such as a proteinaceous compound or an environment A method for removing lipophilic components such as pollutants and cholesterol is described.
- Patent Document 4 describes a method for producing purified fish oil, which comprises contacting fish oil with alkali and then with activated clay, and then contacting the steam with fish oil at 150 to 230° C. by steam distillation to deodorize the fish oil. Has been done.
- Patent Document 5 discloses that an alkyl ester form of a polyunsaturated fatty acid is brought into contact with an aqueous solution containing a silver salt and then vacuum distilled at 170 to 190° C. and a column top vacuum degree of 1 Pa or less to give a trans isomer. It is described that a PUFA alkyl ester-containing composition having a very low content was produced.
- the EPA-containing composition produced by the conventional method contains unknown impurities, and these impurities are known so far. It was found to be a novel EPA analog that is not present. Since the impurity substance is an unknown substance, purification of EPA by paying attention to the impurity substance has not been conventionally performed. Further, since the impurity substance has a chemical structure similar to that of EPA, it is extremely difficult to remove it from the EPA-containing composition. For these reasons, it was speculated that the impurities may have been included in conventional EPA-containing compositions without their knowledge of their presence. By removing these impurities, the purity of the EPA-containing composition can be further improved.
- the present invention provides a high-concentration and high-purity EPA-containing composition from which the above-mentioned conventionally unknown EPA analogs have been removed, and a method for producing the same.
- the present invention provides a method for producing an eicosapentaenoic acid alkyl ester-containing composition, (1) recovering an aqueous layer after bringing a feedstock oil containing eicosapentaenoic acid alkyl ester into contact with an aqueous solution containing a silver salt; (2) recovering the organic solvent layer after adding the organic solvent to the aqueous layer; and (3) vacuum distilling the organic solvent layer at a temperature of 180 to 188° C. and a top vacuum degree of 0.7 Pa or less. And recovering the eicosapentaenoic acid alkyl ester from the organic solvent layer, And a method including.
- the present invention has a content of alkyl ester of eicosapentaenoic acid of 95% by area or more, and (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester.
- an eicosapentaenoic acid alkyl ester-containing composition in which the content of each of 7,10,13,16,19-hexaenoic acid alkyl ester is 0.1 area% or less.
- the present invention is a method for measuring the purity of an eicosapentaenoic acid alkyl ester-containing composition, wherein (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13, 16-pentaenoic acid alkyl ester, (7Z,10Z,13Z,16Z,19Z)-ikosa-7,10,13,16,19-pentaenoic acid alkyl ester, and (4Z,7Z,10Z,13Z,16Z,19Z) -Echosa-4,7,10,13,16,19-providing a method comprising measuring the content of at least one substance selected from the group consisting of alkyl esters of hexaenoic acid.
- the present invention is (4Z,7Z,10Z,13Z,16Z)-ikosa-4,7,10,13,16-pentaenoic acid alkyl ester, (7Z,10Z,13Z,16Z,19Z)-ikosa-7, Provided is 10,13,16,19-pentaenoic acid alkyl ester, or (4Z,7Z,10Z,13Z,16Z,19Z)-equosa-4,7,10,13,16,19-hexaenoic acid alkyl ester.
- a high-concentration, high-purity EPA-containing composition containing as little fatty acid as possible that may adversely affect the living body is useful as a raw material for medicines and health foods.
- arachidonic acid which has been conventionally removed as an impurity
- the concentration of EPA-related substances that have not been recognized as impurities has been reduced, and a higher concentration and higher purity EPA-containing composition has been obtained. Things are offered.
- the present invention relates to unknown impurities contained in a conventional eicosapentaenoic acid (EPA) alkyl ester-containing composition.
- EPA eicosapentaenoic acid
- a high-concentration and high-purity eicosapentaenoic acid (EPA)-containing composition containing as little impurities as possible such as fatty acids and trans isomers that may adversely affect the living body is useful as a raw material for pharmaceuticals and health foods.
- the present inventors have detected and identified impurities contained in the conventional EPA-containing composition in order to search for a higher-purity EPA-containing composition.
- the present inventor has found that the EPA alkyl ester-containing composition obtained by the conventional method (for example, the method described in Patent Document 5) contains the following unknown impurities.
- Impurities of the present invention can be separated from the EPA alkyl ester-containing composition. Since the impurities of the present invention have a structure similar to that of EPA, it is extremely difficult to separate it from EPA by the conventional purification method of EPA, which has hitherto been separated or identified. It was presumed to be the reason why it was not done.
- the present inventor has conducted research on a method of removing the impurities of the present invention from an EPA alkyl ester-containing composition in order to produce a higher purity EPA-containing composition, and has improved the EPA alkyl ester-containing composition.
- one aspect of the present invention relates to a method for producing an EPA alkyl ester-containing composition having a reduced content of impurities according to the present invention. Further, another aspect of the present invention relates to the EPA alkyl ester-containing composition of the present invention, which is produced by the production method and has a reduced content of impurities.
- the raw material oil of the composition containing the EPA alkyl ester can be prepared from the biological fat or oil containing the EPA.
- the organism-derived oils and fats include oils and fats derived from marine animals such as fish and plankton, oils and fats derived from microorganisms such as algae, among others, sardines, mackerel, oils and fats derived from fish such as tuna, and oils and fats derived from algae are preferred examples.
- These bio-based fats and oils mainly contain fatty acid in the form of triglyceride in which one molecule of glycerin is bound with three molecules of fatty acid. It may contain a small amount of diglyceride, monoglyceride or free fatty acid.
- the biological fat and oil contains 20% by area or more of EPA in all contained fatty acids.
- EPA may be present in the biological fat or oil in the form of free fatty acids, or in the form of fatty acid chains of mono-, di- or triglycerides.
- the ratio of each constituent fatty acid to the total fatty acids in the oil or fat can be measured by gas chromatography under the conditions described below.
- the biological fat or oil is prepared as a raw material oil in the production method of the present invention by alkyl-esterifying the contained EPA and concentrating the EPA if necessary.
- the EPA alkyl ester can be produced, for example, by subjecting a fat or oil containing EPA and an acid having a desired alkyl group to an esterification reaction by a known method.
- an EPA alkyl ester can be obtained by reacting EPA in a glyceride contained in the biological fat and oil with a lower alcohol in the presence of a catalyst or an enzyme to form an alkyl ester.
- the oil/fat containing the EPA alkyl ester used as the raw material oil a commercially available oil/fat may be used. From the viewpoint of obtaining a high content of alkyl ester of EPA, it is preferable to use a commercially available oil and fat derived from fish oil in which the amount of EPA contained is standardized.
- the raw material oil used in the production method of the present invention is preferably an oil and fat containing 40 area% or more of EPA in the total fatty acids contained. In the production method of the present invention, by using a feedstock oil having an EPA content of 40% by area or more in all fatty acids, a composition containing EPA in a high concentration can be efficiently obtained finally.
- the above-mentioned raw material oil is preferably applied in a liquid form.
- the feed oil is in a liquid form at the reaction temperature in each step, it can be directly applied to each step of the present invention.
- the raw material oil may be appropriately dissolved or diluted in an organic solvent or another oil and applied.
- the organic solvent an organic solvent that can be separated from water is used in order to carry out the following step (1), and examples thereof include ethyl acetate, chloroform, carbon tetrachloride, diethyl ether, and hexane.
- the method of making the EPA alkyl ester-containing composition of the present invention comprises: (1) recovering an aqueous layer after contacting a feedstock oil containing an EPA alkyl ester with an aqueous solution containing a silver salt; (2) recovering the organic solvent layer after adding the organic solvent to the aqueous layer; and (3) vacuum distilling the organic solvent layer at a temperature of 180 to 188° C. and a top vacuum degree of 0.7 Pa or less. And recover the EPA alkyl ester from the organic solvent layer.
- the steps (1) and (2) are carried out by forming a complex with a silver salt at a carbon-carbon double bond portion of a polyunsaturated fatty acid (PUFA) to form a PUFA alkyl containing EPA.
- PUFA polyunsaturated fatty acid
- This is a step of separating and purifying the EPA alkyl ester from the feed oil by utilizing the fact that the solubility of the ester in the extraction solvent changes.
- the step (1) is a step of recovering an aqueous layer after bringing a feedstock oil containing an EPA alkyl ester into contact with an aqueous solution containing a silver salt.
- This step can be performed according to the method described in, for example, Japanese Patent No. 2786748, Japanese Patent No. 2895258, Japanese Patent No. 2935555, Japanese Patent No. 3001954, or the like.
- an aqueous solution containing a silver salt is added to the above-mentioned stock oil containing EPA alkyl ester, and stirred for 5 minutes to 4 hours, preferably 10 minutes to 2 hours.
- the reaction temperature at this time is, for example, about 80° C. or lower, with the upper limit being the temperature at which the product of the step (1) becomes completely liquid, while the lower limit is preferably 5° C. or higher. More preferably, the reaction temperature is around room temperature (20 to 30° C.).
- the reaction produces a silver-EPA complex. Since the complex is dissolved in the layer of the aqueous solution, EPA can be selectively recovered by recovering the aqueous layer from the solution.
- the silver salt is not particularly limited as long as it can form a complex with the unsaturated bond of PUFA, and silver nitrate, silver perchlorate, silver tetrafluoroborate, silver acetate and the like can be used. Of these, silver nitrate is preferred.
- the solvent of the aqueous solution include water or a mixed medium of water and a compound having a hydroxyl group such as glycerin or ethylene glycol, and water is preferably used.
- the concentration of silver salt in the aqueous solution may be 0.1 mol/L or more, but is preferably about 1 to 20 mol/L.
- the molar ratio of PUFA to silver salt is about 1:100 to 100:1, preferably about 1:5 to 1:1.
- step (2) of the production method of the present invention an organic solvent is added to the aqueous layer recovered in the above step (1) to extract the EPA alkyl ester in the aqueous layer into the organic solvent layer, and then the EPA. It is a step of recovering an organic solvent layer containing an alkyl ester.
- This step can be performed according to the method described in, for example, Japanese Patent No. 2786748, Japanese Patent No. 2895258, Japanese Patent No. 2935555, Japanese Patent No. 3001954, or the like.
- the organic solvent added to the aqueous layer examples include hexane, ether, ethyl acetate, butyl acetate, chloroform, cyclohexane, benzene, toluene, xylene and the like, which have high solubility in PUFA and are separable from water.
- the solution (reaction solution) added with the organic solvent is heated to a temperature higher than the reaction temperature in the step (1), that is, the temperature at which the silver-EPA complex is formed. More preferably, the reaction temperature in step (1), that is, the temperature at which the temperature of forming the complex is higher by 20° C. or more.
- the temperature of the reaction solution in the step (2) is preferably 40° C. or higher, more preferably about 50 to 80° C.
- the extraction reaction time of the EPA alkyl ester into the organic solvent layer may be 10 minutes to 6 hours, preferably 30 minutes to 2 hours, and the solution may be stirred during the reaction. Then, the aqueous layer is removed, and the organic solvent layer containing the EPA alkyl ester is recovered. Alternatively, the residual silver ions may be further removed by passing the recovered organic solvent layer through an adsorbent such as silica gel, activated carbon, or silicon dioxide.
- steps (1) and (2) above are performed according to the method described in WO2017/191821 instead of batch mixing the feedstock and the aqueous solution or the aqueous solution and the organic solvent as described above. May be done. That is, a droplet of an aqueous solution containing a silver salt is passed through a feedstock oil containing an EPA alkyl ester in a first reaction vessel to bring the aqueous solution into contact with the feedstock oil to form a silver-EPA complex. An aqueous solution containing is produced and is recovered.
- a droplet of the aqueous solution containing the recovered silver-EPA complex is passed through the organic solvent in the second reaction tank to extract the EPA alkyl ester into the organic solvent, and then the EPA alkyl is extracted.
- the organic solvent layer containing the ester is collected.
- the droplets of the aqueous solution are passed through the feedstock oil, and the aqueous solution containing the silver-EPA complex is recovered, and/or the droplets of the aqueous solution containing the silver-EPA complex are collected in an organic solvent.
- the recovery of the organic solvent layer containing the EPA alkyl ester are carried out in parallel while optionally adding an aqueous solution and optionally a feed oil or an organic solvent to the first and/or second reaction tank, And preferably it is carried out continuously.
- the passage time of the aqueous solution in the first and second reaction tanks is the difference in specific gravity between the aqueous solution and the feed oil or the organic solvent, and the volume of the feed oil or the organic solvent.
- it can be controlled according to (size of reaction tank), it can also be controlled by controlling the flow rate and flow rate of the aqueous solution in the reaction tank and, if necessary, the feed oil or the organic solvent with a pump or the like.
- the temperatures of the liquids in the first and second reaction tanks may be the same as the temperatures of the reaction liquids of the steps (1) and (2) described above, respectively.
- the aqueous solution containing the silver salt after being brought into contact with the organic solvent can be repeatedly reused and used again for contact with the feedstock oil. Therefore, in the present embodiment, the amount of the aqueous solution containing the silver salt used is reduced to about 1/2 to 1/20 as compared with the method in which the aqueous solution containing the silver salt is collectively added to the raw material oil and stirred. It is possible to
- the step (3) of the production method of the present invention is a step of vacuum-distilling the organic solvent layer obtained in the step (2) to recover the target EPA alkyl ester. More specifically, the target EPA alkyl ester is selectively recovered from the organic solvent layer containing the EPA alkyl ester obtained in step (2) due to the difference in boiling point.
- a vacuum distillation apparatus of a known system such as a filling system, a spring system, or a tray system can be used, or a continuous distillation system may be adopted.
- the conditions for vacuum distillation in the method of the present invention are set to a lower pressure and a temperature in a more restricted range as compared with the conventional vacuum distillation method (for example, the method described in Patent Document 5). That is, in the method of the present invention, the vacuum distillation conditions in the step (3) are such that the top vacuum of the distillation machine is 0.7 Pa or less and the distillation temperature is 180 to 188°C, preferably 185 to 188°C. ..
- the degree of vacuum at the top of the column exceeds 0.7 Pa, the separation from the impurities of the present invention becomes poor and it becomes difficult to recover the high-purity EPA alkyl ester. Further, if the distillation temperature is lower than 180°C, the distillation time required for concentrating EPA and removing the impurities of the present invention becomes long, while if it exceeds 188°C, the distillation efficiency is improved although the energy cost increases. No, the cost is high.
- the distillation temperature in this step is represented as the temperature of the organic solvent layer containing the EPA alkyl ester.
- the fraction containing the EPA alkyl ester obtained in the above vacuum distillation step may be refluxed and again subjected to vacuum distillation under the above conditions.
- the above steps are carried out in the order of (1) ⁇ (2) ⁇ (3). If this order is changed, it is impossible to obtain a composition having a high EPA content and a sufficiently low ratio of impurities according to the present invention.
- the step (3) is performed before the step (1) or (2), it becomes difficult to obtain a composition having a high EPA content, or the EPA content is high.
- the composition also has a high content of impurities.
- the EPA alkyl ester-containing composition produced by the production method of the present invention preferably contains 95% by area or more, more preferably 96 area% or more, and even more preferably 98 area% of the EPA alkyl ester in the total fatty acids contained therein. Or more, more preferably 99 area% or more.
- the content of a given fatty acid in an oil/fat composition is the ratio of the peak area of the fatty acid to the total peak area of all fatty acids in the composition measured by gas chromatography under the following conditions ( Area%).
- Area% Area %.
- the column conditions and detection conditions may be as follows.
- the content of the impurities of the present invention in the EPA alkyl ester-containing composition is (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester, (7Z, 10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid alkyl ester, and (4Z,7Z,10Z,13Z,16Z,19Z)-equosa-4,7,10,13 It is 0.1 area% or less for all of the 16,16,19-hexaenoic acid alkyl esters.
- the content of (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester is 0.1% by area or less.
- the content of (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid alkyl ester is 0.07 area% or less, (4Z,7Z,10Z ,13Z,16Z,19Z)-equosa-4,7,10,13,16,19-hexaenoic acid alkyl ester content is 0.09 area% or less.
- the content of (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester is 0.05% by area.
- the content of (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid alkyl ester is 0.07 area% or less
- (4Z,7Z The content of (10Z,13Z,16Z,19Z)-equosa-4,7,10,13,16,19-hexaenoic acid alkyl ester is 0.08 area% or less.
- the EPA alkyl ester-containing composition has an EPA alkyl ester content of 95 area% or more, preferably 96 area% or more, more preferably 98 area% or more, still more preferably 99 area% or more.
- the EPA alkyl ester-containing composition has an EPA alkyl ester content of 95 area% or more, preferably 96 area% or more, more preferably 98 area% or more, still more preferably 99 area% or more.
- the content of (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester is 0.1 area% or less, (7Z,10Z,13Z, 16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid alkyl ester content of 0.07 area% or less, and (4Z,7Z,10Z,13Z,16Z,19Z)-equosa
- the content of -4,7,10,13,16,19-hexaenoic acid alkyl ester is 0.09 area% or less.
- the EPA alkyl ester-containing composition has a content of EPA alkyl ester of 98 area% or more, preferably 99 area% or more, and is (4Z,7Z,10Z,13Z,16Z)-equosa-
- the content of 4,7,10,13,16-pentaenoic acid alkyl ester is 0.05 area% or less, (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19 -
- the content of alkyl pentaenoic acid ester is 0.07 area% or less, and (4Z,7Z,10Z,13Z,16Z,19Z)-Icosa-4,7,10,13,16,19-alkyl hexaenoic acid
- the ester content is 0.08 area% or less.
- the present inventor has found that the impurities of the present invention are related substances of EPA that are extremely difficult to separate from EPA, and therefore their content can be an index of the purity of the EPA alkyl ester-containing composition. It was Therefore, a further aspect of the present invention relates to a method of measuring the purity of an EPA alkyl ester-containing composition, which comprises measuring the content of impurities of the present invention.
- the content of the substance can be calculated, for example, from the ratio of the peak area of the substance to the total peak area of all fatty acids measured by gas chromatography under the above-mentioned conditions.
- the content of the measured substance in the EPA alkyl ester-containing composition indicates the mixing level of the measured substance with respect to the target EPA, which is a substance in which the impurities of the present invention are extremely difficult to separate from the EPA. Taking this into account, it reflects the purity of the EPA of interest in the composition.
- (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester in the EPA alkyl ester-containing composition (7Z,10Z,13Z, 16Z,19Z)-Ikosa-7,10,13,16,19-pentaenoic acid alkyl ester, and (4Z,7Z,10Z,13Z,16Z,19Z)-Ikosa-4,7,10,13,16,19 -
- the content of any of the hexaenoic acid alkyl ester is 0.5 area% or less, preferably 0.3 area% or less, more preferably 0.1 area% or less
- the EPA alkyl ester-containing composition is It is evaluated to have high purity.
- the EPA alkyl ester-containing composition is evaluated to have sufficiently high purity as a raw material for medicines or foods.
- (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester in the EPA alkyl ester-containing composition (7Z,10Z,13Z ,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid alkyl ester, and (4Z,7Z,10Z,13Z,16Z,19Z)-equosa-4,7,10,13,16, When the content of the 19-hexaenoic acid alkyl ester is 0.5 area% or less, preferably 0.3 area% or less, and more preferably 0.1 area% or less, the EPA alkyl ester-containing composition is It is evaluated to have high purity.
- the EPA alkyl ester-containing composition is evaluated to have sufficiently high purity as a raw material for medicines or foods.
- the content of (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester in the EPA alkyl ester-containing composition is 0.1.
- the EPA alkyl ester-containing composition The product is evaluated as having high purity. More specifically, the EPA alkyl ester-containing composition is evaluated to have sufficiently high purity as a raw material for medicines or foods.
- the content of (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester in the EPA alkyl ester-containing composition is 0.05.
- the EPA alkyl ester-containing composition The product is evaluated as having high purity. More specifically, the EPA alkyl ester-containing composition is evaluated to have sufficiently high purity as a raw material for medicines or foods.
- the content of EPA alkyl ester in the composition containing EPA alkyl ester may be further measured.
- the content of the EPA alkyl ester in the EPA alkyl ester-containing composition is 95 area% or more, preferably 96 area% or more, more preferably 98 area% or more, still more preferably 99 area%.
- the EPA alkyl ester-containing composition is evaluated to have sufficiently high purity as a raw material for medicines or foods.
- the content of EPA alkyl ester in the EPA alkyl ester-containing composition is 95 area% or more, preferably 96 area% or more, more preferably 98 area% or more, still more preferably 99 area% or more.
- the content of (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaenoic acid alkyl ester is 0.1 area% or less, (7Z,10Z,13Z, 16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid alkyl ester content of 0.07 area% or less, and (4Z,7Z,10Z,13Z,16Z,19Z)-equosa If the content of -4,7,10,13,16,19-hexaenoic acid alkyl ester is 0.09 area% or less, the EPA alkyl ester-containing composition is evaluated to have high purity.
- the EPA alkyl ester-containing composition is evaluated to have sufficiently high purity as a raw material for medicines or foods.
- the content of EPA alkyl ester in the EPA alkyl ester-containing composition is 98 area% or more, more preferably 99 area% or more, and (4Z,7Z,10Z,13Z,16Z)-equosa -4,7,10,13,16-pentaenoic acid alkyl ester content is not more than 0.05 area%, (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,
- the content of 19-pentaenoic acid alkyl ester is 0.07 area% or less, and (4Z,7Z,10Z,13Z,16Z,19Z)-ikosa-4,7,10,13,16,19-hexaenoic acid
- the EPA alkyl ester-containing composition is 98 area% or more, more preferably 99 area% or more, and (4Z,
- Reference Example 1 Fatty Acid Composition Analysis 9 ⁇ L of a measurement sample was diluted with 1.5 mL of n-hexane, and a fatty acid was analyzed under the following conditions using a gas chromatography analyzer (Type 6890 GC; manufactured by Agilent Technologies). The fatty acid content was calculated as the ratio (area%) of the peak area of each fatty acid to the total peak area of all fatty acids in the chromatogram.
- ⁇ Column condition> Column: J&W DB-WAX 0.25mm ⁇ 60m (Capillary column with a 0.25 mm inner diameter and 60 m long fused silica tube coated with polyethylene glycol to a film thickness of 0.25 ⁇ m) Column temperature: 210°C He flow rate: 1.3 mL/min ⁇ Detection conditions> H 2 flow rate: 30 mL/min, Air flow rate: 400 mL/min DET temperature: 260°C Alternatively, ⁇ Column condition> Column: GL Sciences TC-2560 0.25mm ⁇ 100m ⁇ 0.20 ⁇ m (Chemical column of non-chemical bond type in which cyanopropyl is coated in a thickness of 0.20 ⁇ m on a fused silica tube with an inner diameter of 0.25 mm and a length of 100 m) Column temperature: 170°C (150min hold) ⁇ Temperature rise (10°C/min) ⁇ 240°C(15min hold) He flow rate: 1.0 to 1.5 mL
- Reference Example 2 Preparation of stock oil To 2 kg of sardine oil, 2000 mL of anhydrous ethanol solution in which 100 g of sodium hydroxide was dissolved was added and mixed and stirred at 70 to 80° C. for 1 hour. Let stand for hours. The separated aqueous layer was removed, and the oil layer was washed several times with water to neutralize the washing liquid, to obtain ethyl esterified sardine oil.
- the fatty acid composition of the sardine oil was examined according to Reference Example 1. As shown in Table 1, the sardine oil contained 20.4 area% EPA in all fatty acids, and also (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaene.
- Acid 0.047 area% (compared to EPA 0.0023), (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid 0.018 area% (compared to EPA ratio 0.0009) and 0.04 area% of (4Z,7Z,10Z,13Z,16Z,19Z)-equosa-4,7,10,13,16,19-hexaenoic acid (compared to EPA ratio of 0.009). 0012) contained.
- the crude product contained 44.0 area% of EPA in all fatty acids, and (4Z,7Z,10Z,13Z,16Z)-ikosa-4,7,10,13,16- Pentaenoic acid 0.097 area% (EPA ratio 0.0022), (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid 0.040 area% ( EPA ratio 0.0009), and (4Z,7Z,10Z,13Z,16Z,19Z)-equosa-4,7,10,13,16,19-hexaenoic acid 0.053 area% (to EPA ratio 0 .0012) contained.
- This refined product was used as a feedstock in the following examples.
- Example 1 Production of EPA-Containing Composition Step (1): To 300 g of the raw material oil obtained in Reference Example 2, 160 mL of n-hexane was added, mixed well and dissolved. 500 mL of 50 mass% silver nitrate aqueous solution was added thereto, and the mixture was stirred at 5 to 30°C. After allowing the mixed solution to stand, the separated n-hexane layer was removed and the aqueous layer was recovered. Step (2): 2000 mL of n-hexane was newly added to the recovered aqueous layer and mixed well at 52 to 68° C., and the fatty acid ethyl ester in the aqueous layer was extracted into n-hexane.
- the separated aqueous layer was removed and the n-hexane layer was concentrated.
- the fatty acid composition of the n-hexane layer obtained in the step (2) was examined.
- the fatty acid ethyl ester contained in the n-hexane layer contained 74.5 area% of EPA in all the fatty acids, and (4Z,7Z,10Z,13Z,16Z)-ikosa-4.
- Step (3) The n-hexane layer containing the fatty acid ethyl ester obtained in Step (2) was subjected to a column top precision distillation machine under conditions of a column top vacuum of 0.7 Pa or less and a distillation temperature of 180 to 183° C. Vacuum distillation was performed while maintaining the above to obtain an EPA ethyl ester-containing composition.
- the fatty acid composition of the composition obtained according to Reference Example 1 was investigated. As shown in Table 1, the composition contained 98.4 area% EPA in all fatty acids, and also contained (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaene.
- Acid 0.098 area% (compared to EPA 0.0010), (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid 0.069 area% (compared to EPA ratio 0.0007), 0.04 area% of (4Z,7Z,10Z,13Z,16Z,19Z)-equosa-4,7,10,13,16,19-hexaenoic acid (ratio to EPA 0.0009). ) Contained.
- Example 2 In the step (3), an EPA ethyl ester-containing composition was obtained by the same procedure as in Example 1 except that the column top vacuum degree was 0.7 Pa and the distillation temperature was 180° C. to 188° C.
- the fatty acid composition of the composition obtained according to Reference Example 1 was investigated. As shown in Table 1, the composition contained 98.2 area% EPA in all fatty acids, and also contained (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaene.
- Acid 0.079 area% (compared to EPA 0.0008), (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid 0.069 area% (compared to EPA ratio 0.0007), 0.04 area% of (4Z,7Z,10Z,13Z,16Z,19Z)-equosa-4,7,10,13,16,19-hexaenoic acid (ratio to EPA 0.0009). ) Contained.
- Example 3 In the step (3), an EPA ethyl ester-containing composition was obtained by the same procedure as in Example 1 except that the overhead vacuum was 0.7 Pa and the distillation temperature was 185° C. to 188° C.
- the fatty acid composition of the composition obtained according to Reference Example 1 was investigated. As shown in Table 1, the composition contained 99.0 area% EPA in all fatty acids, and also contained (4Z,7Z,10Z,13Z,16Z)-equosa-4,7,10,13,16-pentaene.
- Acid 0.050 area% (compared to EPA 0.0005), (7Z,10Z,13Z,16Z,19Z)-equosa-7,10,13,16,19-pentaenoic acid 0.069 area% (compared to EPA ratio 0.0007), (4Z,7Z,10Z,13Z,16Z,19Z)-equosa-4,7,10,13,16,19-hexaenoic acid 0.079 area% (compared to EPA 0.0008) ) Contained.
- Comparative Example 1 In the step (3), an EPA ethyl ester-containing composition was obtained by the same procedure as in Example 1 except that the column top vacuum degree was 0.9 to 1.0 Pa and the distillation temperature was 172°C to 188°C.
- the fatty acid composition of the composition obtained according to Reference Example 1 was investigated. As shown in Table 1, the composition had a high EPA content of 98.3% in total fatty acids, but it was an impurity (4Z,7Z,10Z,13Z,16Z)-ikosa-4,7.
- step (2) of Example 1 the ratio of impurities to EPA was almost the same as that of the feedstock, and impurities were concentrated together with EPA.
- step (3) of Example 1 the EPA was concentrated while the impurities were reduced, which indicates that the impurities were separated from the EPA in the step (3).
- the ratio of impurities to EPA in Comparative Example 1 was almost the same as that of the feed oil and the step (2), it was found that the vacuum distillation conditions in the step (3) are important for the separation of impurities. Was shown.
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Abstract
Description
(1)エイコサペンタエン酸アルキルエステルを含有する原料油を、銀塩を含む水溶液と接触させた後、水層を回収すること;
(2)該水層に有機溶媒を添加した後、有機溶媒層を回収すること;及び
(3)該有機溶媒層を、温度180~188℃、塔頂真空度0.7Pa以下で真空蒸留して、該有機溶媒層からエイコサペンタエン酸アルキルエステルを回収すること、
を含む方法、を提供する。
また本発明は、エイコサペンタエン酸のアルキルエステルの含有量が95面積%以上であり、かつ(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が、それぞれ0.1面積%以下である、エイコサペンタエン酸アルキルエステル含有組成物を提供する。
また本発明は、エイコサペンタエン酸アルキルエステル含有組成物の純度を測定する方法であって、該組成物における、(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルからなる群より選択される少なくとも1種の物質の含有量を測定することを含む方法、を提供する。
また本発明は、(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、又は(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルを提供する。
(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、
(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、
(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステル。
これら3つの物質は、いずれもEPAの類縁物質であり、かつ従来知られていない新規物質であった。以下の本明細書において、これら3つの物質をまとめて、本発明の不純物質とも称する。本発明の不純物質は、EPAアルキルエステル含有組成物から分離されたものであり得る。本発明の不純物質は、EPAと構造が類似しているために従来のEPAの精製方法ではEPAと分離することが極めて困難であり、それが、これまでに本発明の不純物質が分離又は同定されていなかった理由であろうと推定された。
(1)EPAアルキルエステルを含有する原料油を、銀塩を含む水溶液と接触させた後、水層を回収すること;
(2)該水層に有機溶媒を添加した後、有機溶媒層を回収すること;及び
(3)該有機溶媒層を、温度180~188℃、塔頂真空度0.7Pa以下で真空蒸留して、該有機溶媒層からEPAアルキルエステルを回収すること。
<試料>
測定試料9μLをn-ヘキサン1.5mLに希釈
<カラム条件>
カラム :内径0.25mm、長さ60mの溶融シリカ管に、ポリエチレン
グリコールを膜厚0.25μmに被膜したキャピラリーカラム
(例えば、J&W社製DB-WAX)
カラム温度:210℃
He流量 :1.3mL/min
<検出条件>
H2流量:30mL/min、 Air流量:400mL/min
DET温度:260℃
あるいは、カラム条件と検出条件は下記のとおりでもよい。
<カラム条件>
カラム :内径0.25mm、長さ100mの溶融シリカ管に、シアノプロピル
を膜厚0.20μmに被膜した非化学結合タイプのキャピラリー
カラム(例えば、ジーエルサイエンス社製TC-2560
0.25mm×100m×0.20μm)
カラム温度:170℃(150min hold)→昇温(10℃/min)
→240℃(15min hold)
He流量 :1.0~1.5mL/min
<検出条件>
H2流量:30mL/min、 Air流量:400mL/min
DET温度:270℃
より好ましい実施形態においては、EPAアルキルエステル含有組成物中における(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が、いずれも0.5面積%以下、好ましくは0.3面積%以下、より好ましくは0.1面積%以下であれば、該EPAアルキルエステル含有組成物は高純度であると評価される。より詳細には、該EPAアルキルエステル含有組成物は、医薬又は食品の原料として充分に高純度であると評価される。
さらに好ましい実施形態においては、EPAアルキルエステル含有組成物中における(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステルの含有量が0.1面積%以下であり、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステルの含有量が0.07面積%以下であり、かつ(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が0.09面積%以下であれば、該EPAアルキルエステル含有組成物は高純度であると評価される。より詳細には、該EPAアルキルエステル含有組成物は、医薬又は食品の原料として充分に高純度であると評価される。
さらに好ましい実施形態においては、EPAアルキルエステル含有組成物中における(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステルの含有量が0.05面積%以下であり、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステルの含有量が0.07面積%以下であり、かつ(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が0.08面積%以下であれば、該EPAアルキルエステル含有組成物は高純度であると評価される。より詳細には、該EPAアルキルエステル含有組成物は、医薬又は食品の原料として充分に高純度であると評価される。
さらに好ましい実施形態においては、EPAアルキルエステル含有組成物中におけるEPAアルキルエステルの含有量が95面積%以上、好ましくは96面積%以上、より好ましくは98面積%以上、さらに好ましくは99面積%以上であり、(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステルの含有量が0.1面積%以下であり、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステルの含有量が0.07面積%以下であり、かつ(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が0.09面積%以下であれば、該EPAアルキルエステル含有組成物は高純度であると評価される。より詳細には、該EPAアルキルエステル含有組成物は、医薬又は食品の原料として充分に高純度であると評価される。
さらに好ましい実施形態においては、EPAアルキルエステル含有組成物中におけるEPAアルキルエステルの含有量が98面積%以上、さらに好ましくは99面積%以上であり、(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステルの含有量が0.05面積%以下であり、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステルの含有量が0.07面積%以下であり、かつ(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が0.08面積%以下であれば、該EPAアルキルエステル含有組成物は高純度であると評価される。より詳細には、該EPAアルキルエステル含有組成物は、医薬又は食品の原料として充分に高純度であると評価される。
測定試料9μLをn-ヘキサン1.5mLに希釈し、ガスクロマトグラフィー分析装置(Type 6890 GC;Agilent Technologies製)を用いて、以下の条件にて脂肪酸を分析した。脂肪酸の含有量は、クロマトグラムにおける全脂肪酸の合計ピーク面積に対する各脂肪酸のピーク面積の割合(面積%)として算出した。
<カラム条件>
カラム:J&W社製DB-WAX 0.25mm×60m
(内径0.25mm、長さ60mの溶融シリカ管に、ポリエチレン
グリコールを膜厚0.25μmに被膜したキャピラリーカラム)
カラム温度:210℃
He流量:1.3mL/min
<検出条件>
H2流量:30mL/min、 Air流量:400mL/min
DET温度:260℃
あるいは、
<カラム条件>
カラム:ジーエルサイエンス社製TC-2560 0.25mm×100m×0.20μm
(内径0.25mm、長さ100mの溶融シリカ管にシアノプロピル
を膜厚0.20μmに被膜した、非化学結合タイプのキャピラリ
ーカラム)
カラム温度:170℃(150min hold)→昇温(10℃/min)
→240℃(15min hold)
He流量:1.0~1.5mL/min
<検出条件>
H2流量:30mL/min、Air流量:400mL/min
DET温度:270℃
イワシ油2kgに、水酸化ナトリウム100gを溶解させた無水エタノール溶液2000mLを加えて70~80℃にて1時間混合攪拌し、さらに水1000mLを加えてよく混合し、1時間静置した。分離した水層を除去し、油層を数回水洗して洗液を中性にし、エチルエステル化イワシ油を得た。参考例1に従って該イワシ油の脂肪酸組成を調べた。該イワシ油は、表1に示すとおり、全脂肪酸中にEPA20.4面積%を含有し、また(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸を0.047面積%(対EPA比0.0023)、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸を0.018面積%(対EPA比0.0009)、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸を0.024面積%(対EPA比0.0012)含有していた。
工程(1):参考例2で得た原料油300gにn-ヘキサン160mLを加え、よく混合して溶解させた。ここに50質量%硝酸銀水溶液500mLを加え、5~30℃の条件下で攪拌した。混合液を静置後、分離したn-ヘキサン層を除去し、水層を回収した。
工程(2):回収した水層に新たにn-ヘキサン2000mLを加えて52~68℃でよく混合し、水層中の脂肪酸エチルエステルをn-ヘキサン中に抽出させた。混合液を静置後、分離した水層を除去し、n-ヘキサン層を濃縮した。
参考例1に従って工程(2)で得たn-ヘキサン層の脂肪酸組成を調べた。該n-ヘキサン層に含まれていた脂肪酸エチルエステルは、表1に示すとおり、全脂肪酸中にEPA74.5面積%を含有し、また(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸を0.156面積%(対EPA比0.0021)、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸を0.067面積%(対EPA比0.0009)、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸を0.089面積%(対EPA比0.0012)含有していた。
工程(3)において、塔頂真空度0.7Paとし、蒸留温度を180℃~188℃とした以外は、実施例1と同様の手順でEPAエチルエステル含有組成物を得た。参考例1に従って得られた組成物の脂肪酸組成を調べた。該組成物は、表1に示すとおり、全脂肪酸中にEPA98.2面積%を含有し、また(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸を0.079面積%(対EPA比0.0008)、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸を0.069面積%(対EPA比0.0007)、(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸を0.088面積%(対EPA比0.0009)含有していた。
工程(3)において、塔頂真空度0.7Paとし、蒸留温度を185℃~188℃とした以外は、実施例1と同様の手順でEPAエチルエステル含有組成物を得た。参考例1に従って得られた組成物の脂肪酸組成を調べた。該組成物は、表1に示すとおり、全脂肪酸中にEPA99.0面積%を含有し、また(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸を0.050面積%(対EPA比0.0005)、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸を0.069面積%(対EPA比0.0007)、(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸を0.079面積%(対EPA比0.0008)含有していた。
工程(3)において、塔頂真空度0.9~1.0Paとし、蒸留温度を172℃~188℃とした以外は、実施例1と同様の手順でEPAエチルエステル含有組成物を得た。参考例1に従って得られた組成物の脂肪酸組成を調べた。該組成物は、表1に示すとおり、全脂肪酸中のEPAの含有量は98.3%と高かったが、不純物質である(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸の含有量は、それぞれ0.157面積%(対EPA比0.0016)、0.088面積%(対EPA比0.0009)、0.108面積%(対EPA比0.0011)であり、(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸が高値であった。
Claims (10)
- エイコサペンタエン酸アルキルエステル含有組成物の製造方法であって、
(1)エイコサペンタエン酸アルキルエステルを含有する原料油を、銀塩を含む水溶液と接触させた後、水層を回収すること;
(2)該水層に有機溶媒を添加した後、有機溶媒層を回収すること;及び
(3)該有機溶媒層を、温度180~188℃、塔頂真空度0.7Pa以下で真空蒸留して、該有機溶媒層からエイコサペンタエン酸アルキルエステルを回収すること、
を含む、方法。 - 前記エイコサペンタエン酸アルキルエステル含有組成物が、エイコサペンタエン酸のアルキルエステルの含有量が95面積%以上であり、かつ(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が、それぞれ0.1面積%以下である、請求項1記載の方法。
- 前記エイコサペンタエン酸アルキルエステル含有組成物が、前記(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステルの含有量が0.1面積%以下であり、前記(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステルの含有量が0.07面積%以下であり、前記(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が0.09面積%以下である、請求項2記載の方法。
- 前記真空蒸留の温度が185~188℃である、請求項1~3のいずれか1項記載の方法。
- 前記原料油が、含有する全脂肪酸中にエイコサペンタエン酸を40面積%以上含有する、請求項1~4のいずれか1項記載の方法。
- エイコサペンタエン酸のアルキルエステルの含有量が95面積%以上であり、かつ(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が、それぞれ0.1面積%以下である、エイコサペンタエン酸アルキルエステル含有組成物。
- 前記(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステルの含有量が0.1面積%以下であり、前記(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステルの含有量が0.07面積%以下であり、前記(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルの含有量が0.09面積%以下である、請求項6記載の組成物。
- エイコサペンタエン酸アルキルエステル含有組成物の純度を測定する方法であって、該組成物における、(4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、及び(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステルからなる群より選択される少なくとも1種の物質の含有量を測定することを含む、方法。
- エイコサペンタエン酸アルキルエステルの含有量を測定することをさらに含む、請求項8記載の方法。
- (4Z,7Z,10Z,13Z,16Z)-イコサ-4,7,10,13,16-ペンタエン酸アルキルエステル、(7Z,10Z,13Z,16Z,19Z)-イコサ-7,10,13,16,19-ペンタエン酸アルキルエステル、又は(4Z,7Z,10Z,13Z,16Z,19Z)-イコサ-4,7,10,13,16,19-ヘキサエン酸アルキルエステル。
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