WO2013172346A1 - 環境汚染物質を低減させた高度不飽和脂肪酸又は高度不飽和脂肪酸エチルエステル及びその製造方法 - Google Patents
環境汚染物質を低減させた高度不飽和脂肪酸又は高度不飽和脂肪酸エチルエステル及びその製造方法 Download PDFInfo
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- WO2013172346A1 WO2013172346A1 PCT/JP2013/063425 JP2013063425W WO2013172346A1 WO 2013172346 A1 WO2013172346 A1 WO 2013172346A1 JP 2013063425 W JP2013063425 W JP 2013063425W WO 2013172346 A1 WO2013172346 A1 WO 2013172346A1
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- fatty acid
- unsaturated fatty
- highly unsaturated
- ethyl ester
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
-
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/32—Bonded phase chromatography
- B01D15/325—Reversed phase
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
- C07C51/44—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation by distillation
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- C07C57/03—Monocarboxylic acids
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- C07C57/03—Monocarboxylic acids
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- 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
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23D9/00—Other edible oils or fats, e.g. shortenings, cooking oils
- A23D9/02—Other edible oils or fats, e.g. shortenings, cooking oils characterised by the production or working-up
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
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- A61K35/56—Materials from animals other than mammals
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D3/00—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping
- B01D3/14—Fractional distillation or use of a fractionation or rectification column
- B01D3/143—Fractional distillation or use of a fractionation or rectification column by two or more of a fractionation, separation or rectification step
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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
- C07C69/533—Monocarboxylic acid esters having only one carbon-to-carbon double bond
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- 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
- C11B3/16—Refining fats or fatty oils by mechanical means
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
- C11C3/00—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom
- C11C3/003—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom by esterification of fatty acids with alcohols
Definitions
- the present invention relates to the production of highly unsaturated fatty acids or highly unsaturated fatty acid ethyl esters produced from oils and fats containing highly unsaturated fatty acids as raw materials, such as environmental pollutants contained in oils and fats, particularly dioxins, brominated flame retardants, etc. It relates to a method for reducing the amount. Furthermore, the present invention relates to foods, supplements, pharmaceuticals, cosmetics and feeds made from fats and oils prepared according to the method.
- EPA eicosapentaenoic acid, C20: 5, n-3, all-cis-5,8,11,14,17-eicosapentaenoic acid
- DHA docosahexaenoic acid, C22: 6 n-3, all-cis-4,7,10,13,16,19-docosahexaenoic acid
- EPA and DHA are known for various physiological functions and are used as ingredients for pharmaceuticals, health foods, foods, feeds, and the like.
- Various refining steps are applied to utilize EPA and / or DHA in marine oil.
- Non-Patent Document 1 describes the removal of the insecticide DDT and its metabolites from fish oil by molecular distillation.
- Non-Patent Document 2 describes that chlorinated hydrocarbons and free fatty acids can be removed from fats or oils using vacuum stripping or thin film distillation.
- Non-Patent Document 3 describes the use of physical purification and molecular distillation for the removal of undesirable substances such as free fatty acids from oil compositions.
- Patent Document 1 and Non-Patent Document 4 describe a method for reducing environmental pollutants in fats and oils: a process of adding a volatile working fluid to the mixture, and the volatile work to which the mixture has been added. A method is described that includes a process that is subjected to at least one stripping process with a fluid.
- Non-Patent Document 5 describes that highly unsaturated fatty acids are thermally decomposed when fish oil is deodorized at high temperature.
- Non-Patent Document 6 describes that dioxins, free fatty acids, and cholesterol are removed from fish oil by a short stroke distillation method and used as a raw material for ethyl ester.
- Patent No. 3905538 (WO2004 / 007654)
- the present invention relates to a method for reducing environmental pollutants contained in fats and oils, particularly dioxins and brominated flame retardants, and dioxins and brominated products, when producing ethyl esters from fats and oils containing highly unsaturated fatty acids as constituent fatty acids. It is an object to provide an ethyl ester having a low flame retardant content.
- the present invention suppresses denaturation of highly unsaturated fatty acids by performing molecular distillation or short-path distillation under certain conditions in the purification of fats and oils containing highly unsaturated fatty acids that are easily denatured, such as oxidation and isomerization, as constituent fatty acids.
- environmental pollutants can be reduced to a very low concentration.
- the amount of environmental pollutants in fats and oils can be reduced to a total toxic equivalent of less than 0.2 pg-TEQ / g.
- ethyl ester is obtained from the raw material. Dioxins in the ethyl ester can be further reduced by subjecting the ethyl ester to distillation and column chromatography.
- the gist of the present invention is the following highly unsaturated fatty acids or ethyl esters of highly unsaturated fatty acids and methods for producing the same, and feeds, foods, pharmaceuticals and the like containing them.
- a highly unsaturated fatty acid or an ethyl ester of a highly unsaturated fatty acid which is produced using a fat and oil containing a highly unsaturated fatty acid as a constituent fatty acid as a raw material oil, and has a reduced content of environmental pollutants.
- the content of polychlorinated dibenzoparadoxine (PCDD) and polychlorinated dibenzofuran (PCDF) is less than 0.05 pg-TEQ / g
- coplanar PCB (Co-PCB) is less than 0.03 pg-TEQ / g.
- Highly unsaturated fatty acids or ethyl esters of highly unsaturated fatty acids are highly unsaturated fatty acids.
- the content of brominated flame retardant contained is less than 0.18 ng / g for BDE-47, less than 0.03 ng / g for BDE-100, and less than 0.05 ng / g for BDE-49 Or (1) highly unsaturated fatty acids or ethyl esters of highly unsaturated fatty acids, wherein the amount of BDE-99 is reduced to less than 0.05 ng / g.
- the concentration of the highly unsaturated fatty acid in the fatty acid is 80 area% or more, 85 area% or more, 90 area% or more, 95 area% or more, or 96 area% or more, (1) or (2) Ethyl ester of highly unsaturated fatty acid.
- the highly unsaturated fatty acid is one of eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, dihomo- ⁇ -linolenic acid, arachidonic acid, or a combination thereof (1) to (4)
- a pharmaceutical, supplement or food containing the highly unsaturated fatty acid or ethyl ester of the highly unsaturated fatty acid according to any one of (1) to (5) as an active ingredient.
- the concentration of the highly unsaturated fatty acid in the fatty acid of the highly unsaturated fatty acid or ethyl ester of the highly unsaturated fatty acid is 80 area% or more, 85 area% or more, 90 area% or more, 95 area% or more, or 96 area % Or more, the method of (7) or (8).
- a highly unsaturated fatty acid or highly unsaturated fatty acid produced by any of the methods (7) to (16) and having a dioxin content of less than 0.07 pg-TEQ / g or 0.05 pg-TEQ / g Saturated fatty acid ethyl ester.
- the content of brominated flame retardant contained is such that the amount of BDE-47 is less than 0.18 ng / g, the amount of BDE-100 is less than 0.03 ng / g, and the amount of BDE-49 is 0.05 ng / g Or a highly unsaturated fatty acid or ethyl ester of a highly unsaturated fatty acid according to (17), wherein the amount of BDE-99 is reduced to less than 0.05 ng / g.
- the method of the present invention reduces environmental pollutants, especially dioxins, contained in fish oil to a very low level without affecting the content of highly unsaturated fatty acids in fatty acids by distillation at high temperature, high vacuum, and short time. Therefore, it is possible to provide various products such as feeds, foods, supplements, and pharmaceuticals made from fish oil and the like that do not need to worry about contamination by dioxins.
- the highly unsaturated fatty acid is a fatty acid having 18 or more carbon atoms and 3 or more double bonds, more preferably a fatty acid having 20 or more carbon atoms, 3 or more or 4 or more double bonds, particularly preferably. It is a fatty acid having 20 or more carbon atoms and 5 or more double bonds.
- ⁇ -linolenic acid (18: 3, n-3), ⁇ -linolenic acid (18: 3, n-6), dihomo- ⁇ -linolenic acid (20: 3, n-6), arachidonic acid (20: 4, n-6), eicosapentaenoic acid (20: 5, n-3), docosapentaenoic acid (22: 5, n-6), docosahexaenoic acid (22: 6, n-3), etc. Illustrated. These are known to be contained in a large amount in certain microbial oils, vegetable oils, marine animal oils, and the like.
- fish oil such as sardine oil, tuna oil, bonito oil, menhaden oil, cod liver oil, herring oil, caperin oil, and crustacean marine animal oil such as krill, egoma, flax, soybean, rapeseed And oils produced by microorganisms belonging to the genus Mortierella, the genus Penicillium, the genus Aspergillus, the genus Rhodotorula and the genus Fusarium.
- the method of the present invention is particularly suitable for oils and fats derived from marine products where contamination by dioxins is a concern, such as fish oil, krill oil, or marine mammal oil.
- an oil containing a highly unsaturated fatty acid as a constituent fatty acid means triglyceride or phospholipid.
- these fats and oils may be pretreated before being subjected to molecular distillation or short path distillation. Examples of such pretreatment include a degumming step, a decolorization step using activated clay and activated carbon, and a water washing step.
- environmental pollutants include polychlorinated biphenyl (PCB), DDT, polychlorinated triphenyl (PCT), dibenzo-dioxin (PCDD) and dibenzo-furan (PCDF), chlorophenol and hexachlorocyclohexane (HCH). ), Toxaphene, dioxins, brominated flame retardants, polyaromatic hydrocarbons (PAH), organotin compounds (eg tributyltin, triphenyltin), organomercury compounds (eg methylmercury) and the like.
- PCB polychlorinated biphenyl
- PCT polychlorinated triphenyl
- PCDD dibenzo-dioxin
- PCDF dibenzo-furan
- HH hexachlorocyclohexane
- Toxaphene dioxins
- brominated flame retardants polyaromatic hydrocarbons (PAH)
- organotin compounds eg tribu
- dioxins mean the total of polychlorinated dibenzopararadixin (PCDD), polychlorinated dibenzofuran (PCDF) and coplanar PCB (Co-PCB) shown in Table 1, and the content of each component is measured.
- PCDD polychlorinated dibenzopararadixin
- PCDF polychlorinated dibenzofuran
- Co-PCB coplanar PCB
- the toxicity equivalents (pg-TEQ / g) calculated by multiplying the respective measured values by the toxicity equivalents were expressed.
- brominated flame retardant is a general term for compounds as shown in Table 9.
- BDE-100, BDE-49, BDE-99, BDE-47, etc. which are relatively abundant in fish oil, can be used as indicators.
- dioxins are removed by thin film distillation.
- molecular distillation or short path distillation (SPD) is preferable.
- SPD short path distillation
- thin-film distillations distillation performed by placing a condenser within a distance shorter than the mean free path of vapor molecules evaporated from the heating surface at a constant pressure under high vacuum ( ⁇ 0.1 Pa) is called molecular distillation.
- Short stroke distillation was developed to increase the distillation capability of molecular distillation.
- Short-path distillation is performed at a pressure in the middle vacuum range higher than 0.1 Pa, and the condenser is placed at the same distance as the mean free path of the evaporated molecules.
- Method Molecular distillation or short path distillation is suitable for removing unnecessary components from triglycerides containing EPA, DHA, etc., which are sensitive to heat, because the distillate is exposed to a high temperature for a very short time.
- the molecular or short path distillation of the present invention is carried out at a temperature of 200 to 270 ° C., preferably 220 to 260 ° C., particularly preferably 220 to 250 ° C.
- the pressure is 5 Pa, preferably 2 Pa, more preferably 1 Pa.
- the flow rate is 20 to 200 (kg / h) / m 2 , preferably 25 to 120 (kg / h) / m 2 . If the flow rate is too small, the productivity is lowered. Therefore, it is preferable to flow the maximum amount within a range where removal is possible while confirming that dioxins are removed. If distillation is performed under such conditions, although it is a highly unsaturated fatty acid that is weak in temperature, quality degradation hardly occurs.
- PCDD and PCDF could be less than the measurement limit, that is, substantially zero.
- 0 is, for example, less than 0.043 pg-TEQ / g when calculated from the numerical value of the detection limit in Table 6, that is, less than 0.05 pg-TEQ / g.
- Coplanar PCBs can also be reduced to less than 0.2 pg-TEQ / g, further less than 0.1 pg-TEQ / g, less than 0.05 pg-TEQ / g, less than 0.02 pg-TEQ / g, and less than 0.01 pg-TEQ / g.
- brominated flame retardants when BDE-100, BDE-49, BDE-99, BDE-47, etc. are used as indicators, these are less than 0.05 ⁇ g / g, preferably less than 0.03 ⁇ g / g, and further 0.02 ⁇ g / g. Can be reduced to less than
- Embodiments of the method of the present invention are described below. It is preferable to use a raw material oil that has been degummed by a method such as washing with water.
- the raw oil washed with water is subjected to molecular distillation or short-path distillation as it is under the above-mentioned conditions to remove cholesterol, free fatty acids, environmental pollutants and the like as fractions to obtain a residue containing triglycerides.
- This residue may be used as it is, or may be used after decoloring treatment with activated carbon, activated clay, etc., or deodorizing treatment with steam distillation or the like.
- the refined fats and oils thus produced can be used as ingredients for feeds, foods and supplements.
- an ethyl ester with a reduced content of dioxins can be produced using the above residue as a raw material.
- Ethyl alcohol and a catalyst or enzyme are added to the residue and reacted to form a triglyceride fatty acid and an ester of ethyl alcohol.
- Any known method may be used for ethyl esterification. After the ethyl esterification, further purification may be performed as necessary.
- methods such as molecular distillation, rectification, and column chromatography can be used.
- JP-A-5-222392 family patent EP0610506
- JP-A-4-41457 family patent EP0460917
- JP-A-6-33088 JP-A-6-33088 and the like.
- the rectification is carried out in a high-vacuum with three or more distillation columns, and is obtained by separating EPA ethyl ester and / or DHA ethyl ester as the main distillate from the more volatile initial distillate and the less volatile residue. be able to.
- the temperature is 150 to 200 ° C., preferably 160 to 190 ° C., more preferably 170 to 190 ° C.
- the pressure is 1 to 300 Pa, preferably 1 to 200 Pa, more preferably 1 to 133 Pa. is there. It is preferable to obtain a main fraction of 160 to 190 ° C., preferably 170 to 190 ° C. with a vacuum of 1 to 133 Pa.
- Particularly preferred is a method of performing column chromatography after rectification. The inventors of the present application have found that when EPA and DHA are concentrated by rectification, the concentration of dioxins is relatively increased, but by performing column chromatography, the level can be lowered from the level before rectification. .
- silica gel, ion exchange resin, activated clay, silver nitrate, and the like can be used, but column chromatography with a reverse phase distribution system is particularly preferable.
- an alkyl group-bonded silica filler (ODS column or the like) or the like can be used so as to constitute a reverse phase distribution system, and water, alcohol, or ketones can be used as the solvent system. Methanol is preferred. These may be used alone or in combination.
- PCDD and PCDF can be below the measurement limit, that is, substantially zero (less than 0.043 pg-TEQ / g when calculated from the detection limit), and coplanar PCB is also less than 0.1 pg-TEQ / g Furthermore, it can be reduced to less than 0.03 pg-TEQ / g and less than 0.01 pg-TEQ / g.
- the amount of BDE-47 is less than 0.18 ng / g, the amount of BDE-100 is less than 0.03 ng / g, the amount of BDE-49 is less than 0.05 ng / g, or BDE-99
- the amount can be reduced to less than 0.05 ng / g.
- BDE-100, BDE-49, BDE-99, and BDE-47 can be reduced to less than 0.05 ⁇ g / g, preferably less than 0.03 ⁇ g / g, and even less than 0.02 ⁇ g / g.
- the purity of the EPA ethyl ester and / or DHA ethyl ester concentration of 96 area% or more is preferable.
- Such free fatty acids and fatty acid esters having a high concentration of highly unsaturated fatty acids and a low concentration of environmental pollutants are suitable for pharmaceuticals and supplement raw materials containing highly unsaturated fatty acids as active ingredients.
- the highly unsaturated fatty acid in the glyceride can be concentrated by a method (such as WO2009 / 17102) that selectively concentrates the highly unsaturated fatty acid by lipase reaction.
- a method such as WO2009 / 17102
- the highly unsaturated fatty acid can be obtained by hydrolyzing the ester of the highly unsaturated fatty acid produced by the above method.
- Measurement of Dioxins and Brominated Flame Retardant In the examples of the present invention, the measurement of dioxins was requested to the Japan Food Analysis Center. The measuring method is based on “Provisional Guidelines for Measuring Dioxins in Food (February 2008)” (1999 Hygien No. 138, Hygien No. 200). Measurement of brominated flame retardants was requested from eurofins, an analysis company for foods. The measuring method is based on high resolution mass spectrometry (HRGC / HRMS method).
- the acid value (AV) was measured according to the standard method for analyzing fats and oils (2003 version) (edited by the Japan Oil Chemists' Society).
- Fatty acid composition measurement Fish oil used as a raw material and the fatty acid composition of the oil after processing by short-path distillation were measured by gas chromatography after the fish oil was ethyl esterified. That is, 1 mL of 1N sodium ethylate / ethanol solution was added to 40 ⁇ L of fish oil and stirred for about 30 seconds. Thereafter, 1 mL of 1N hydrochloric acid was added for neutralization, 2 mL of hexane and 3 mL of saturated aqueous ammonium sulfate solution were added, and after stirring and standing, the upper layer was measured by gas chromatography.
- the distillation apparatus used is a short path distillation apparatus (SPD) KD 10 (manufactured by UIC GmbH, distillation surface area of 0.1 m 2 ).
- the distillation conditions (temperature, pressure, flow rate) are shown in Table 2.
- the distillation temperature was fixed at 250 ° C., the pressure was varied from 0.4 to 3.0 Pa, and the flow rate was varied from 25 to 121 (kg / hr) / m 2 .
- Table 2 shows the raw oil and dioxin concentrations after distillation and the acid value. Regardless of the acid value of the feedstock and the amount of dioxins in the feedstock, the dioxins content can be reduced to 0.1 pg-TEQ / g or less under any conditions. It was.
- dioxins were removed under the distillation conditions shown in Table 3 for tuna oil (refined oil subjected to degumming and deoxidation treatment). As shown in Table 3, even tuna oil has a dioxin content of 0.1 pg-TEQ / or less by the method of the present invention (distillation temperature is 250 ° C., pressure is 0.1 Pa, flow rate is 48 (kg / hr) / m 2 ). It was possible to reduce. Further, dioxins were removed from sardine crude oil using another short path distillation apparatus (SPD) KD 6 (manufactured by UIC GmbH, distillation surface area 0.06 m 2 ).
- SPD short path distillation apparatus
- Dioxins were removed from the sardine crude oil under the distillation conditions shown in Table 4 using a centrifugal molecular distillation apparatus MS380 (manufactured by Nippon Vehicle Manufacturing Co., Ltd., distillation surface area 0.11 m 2 ). As shown in Table 4, even when a molecular distillation apparatus was used, the dioxins content could be reduced to 0.2 pg-TEQ / or less as in Examples 1 and 2.
- SPD short-path distillation device KD1800 (made by UIC GmbH, distillation surface 18 m 2 ) was used to perform short path distillation.
- the conditions were a degree of vacuum of 0.7 to 1 Pa, a body temperature of 250 ° C., and a feed rate of about 2000 kg / H (flow rate 110 (kg / h) / m 2 ).
- Tables 5 and 6 show the measurement results of dioxins in crude oil and oil after distillation (SPD oil), respectively.
- the total amount of dioxins was reduced from 3.0 pg-TEQ / g to 0.014 pg-TEQ / g in terms of toxicity equivalent. Further, the acid value of the oil after distillation was 0.2 or less, and the fatty acid composition was not changed.
- EPA ethyl ester was produced using the oil after distillation produced in Example 4 as a raw material.
- the oil distilled by SPD was subjected to an ethanolysis reaction with ethyl alcohol in the presence of an alkali catalyst to obtain an ethyl ester.
- Table 8 shows the results of measuring dioxins of this ethyl ester in the same manner as in Example 4.
- Dioxins are not concentrated in the ethyl esterification and subsequent purification steps, and by using the raw material treated in Example 4, the total amount of dioxins is 0.07 pg-TEQ / g or less in terms of toxic equivalents.
- Table 8 shows the results of using three different lots of raw materials. It was confirmed that by the method of the present invention, 0.006 to 0.021 pg-TEQ / g of EPA ethyl ester can be produced stably with a total amount of dioxins equivalent to toxicity. Even if ND below the measurement limit is calculated by inserting the value of the measurement limit, it only increases by 0.005, which means that 0.01 to 0.026 pg-TEQ / g EPA ethyl ester can be produced. .
- the effect of rectification and column chromatography in the purification step after ethyl ester on the concentration of dioxins was confirmed.
- Sardine crude oil that had been deacidified and decolorized and not thin-film distilled was used as the raw material oil. This is because it is easier to observe the effect of the refining treatment when using fats and oils containing a little more dioxins.
- the feedstock was ethyl esterified with an alkali catalyst.
- the ethyl ester was first subjected to a rectification step, and a fraction containing ethyl ester of a fatty acid having 20 carbon atoms was collected. Subsequently, a fraction of eicosapentaenoic acid ethyl ester was collected by ODS column chromatography. Dioxins were measured at each stage.
- Table 9 shows the total of 4 components (absolute amount and toxic equivalent amount) and dioxins (toxic equivalent amount) with large fluctuations. Compared with the esterification, the components # 105 and # 118 were greatly concentrated by the rectification process. On the other hand, it declined rather in # 77. In rectification, eicosapentaenoic acid ethyl ester and the like and dioxins behave in a similar manner, and it is considered that dioxins are concentrated with the concentration of eicosapentaenoic acid ethyl ester and the like. As a result of column processing, # 77 remained unchanged or increased slightly, while other components decreased greatly. In the column treatment, it is considered that ethyl ester and dioxins showed different behavior and could be separated. Therefore, by combining rectification and column treatment, it is possible to simultaneously concentrate the target ethyl ester and reduce dioxins.
- fats and oils containing highly unsaturated fatty acids as constituent fatty acids such as fish oil containing EPA and DHA, particularly dioxins and brominated flame retardants can be greatly reduced.
- Such fats and oils can be provided. It can be used for feed, food, supplements, pharmaceuticals, and the like.
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Abstract
Description
特許文献1、非特許文献4には、油脂中の環境汚染物質を低減させるための方法であって:揮発性作業流体を該混合物に添加する過程、および該混合物が添加された該揮発性作業流体とともに少なくとも1回のストリッピング処理過程に付される過程を含む方法が記載されている。
非特許文献5には、魚油を高温で脱臭すると高度不飽和脂肪酸が熱分解することが記載されている。
非特許文献6には、短行程蒸留方式で魚油からダイオキシンや遊離脂肪酸、コレステロールを除去し、エチルエステルの原料とすることが記載されている。
本発明は、下記の高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル及びその製造方法、及びそれらを含有する飼料、食品、医薬品等を要旨とする。
(2)さらに、含まれる臭素化難燃剤の含有量がBDE-47の量が0.18ng/g未満、BDE-100の量が0.03ng/g未満、BDE-49の量が0.05ng/g未満、又は、BDE-99の量が0.05ng/g未満に低減されている(1)の高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
(3)脂肪酸中に占める高度不飽和脂肪酸の濃度が80面積%以上、85面積%以上、90面積%以上、95面積%以上、又は96面積%以上である、(1)又は(2)の高度不飽和脂肪酸のエチルエステル。
(4)高度不飽和脂肪酸を構成脂肪酸として含有する油脂が魚油、オキアミ油、海洋哺乳類油又は微生物油である(1)ないし(3)いずれかの高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
(5)高度不飽和脂肪酸がエイコサペンタエン酸、ドコサヘキサエン酸、ドコサペンタエン酸、ジホモ-γ-リノレン酸、アラキドン酸のいずれか、又はこれらの組み合わせである(1)ないし(4)いずれかの高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
(6)(1)ないし(5)いずれかの高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルを有効成分として含有する医薬品、サプリメント又は食品。
b) 得られた高度不飽和脂肪酸含有油脂を加水分解又はエチルエステル化し、
c) 精留及びカラムクロマトグラフィにより精製することにより、
ポリ塩化ジベンゾパラジオキシン(PCDD)、ポリ塩化ジベンゾフラン(PCDF)及びコプラナーPCB(Co-PCB)の含有量を低減させた高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルを製造する方法。
(8)さらに、臭素化難燃剤の含有量も低下させる(7)の方法。
(9)高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルの脂肪酸中に占める高度不飽和脂肪酸の濃度が80面積%以上、85面積%以上、90面積%以上、95面積%以上、又は96面積%以上である、(7)又は(8)の方法。
(10)高度不飽和脂肪酸を構成脂肪酸として含有する原料油が魚油、オキアミ油、海洋哺乳類油又は微生物油である(7)ないし(9)いずれかの方法。
(11)前記薄膜蒸留が、200~270℃、220~260℃、又は220~250℃の温度で実行される、(7)ないし(10)いずれかの方法。
(12)前記薄膜蒸留が、5Pa以下、2Pa以下、又は1Pa以下の圧力で実行される、(7)ないし(11)いずれかの方法。
(13)前記薄膜蒸留が、流速20~200(kg/h)/m2、又は25~120(kg/h)/m2で実行される、(7)ないし(12)いずれかの方法。
(14)前期薄膜蒸留が分子蒸留又は短行程蒸留である(7)ないし(13)いずれかの方法。
(15)精留が、3塔以上の蒸留塔にて行うものである(7)ないし(14)のいずれかの方法。
(16)カラムクロマトグラフィによる精製が、逆相分配系のカラムクロマトグラフィを用いるものである(7)ないし(15)のいずれかの方法。
(18)さらに、含まれる臭素化難燃剤の含有量が、BDE-47の量が0.18ng/g未満、BDE-100の量が0.03ng/g未満、BDE-49の量が0.05ng/g未満、又は、BDE-99の量が0.05ng/g未満に低減されている(17)の高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
(19)脂肪酸中に占める高度不飽和脂肪酸の濃度が80面積%以上、85面積%以上、90面積%以上、95面積%以上、又は96面積%以上である(17)又は(18)の高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
(20)(21)ないし(23)いずれかの高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルを含有する医薬品、サプリメント、又は食品。
本発明において、高度不飽和脂肪酸とは、炭素数18以上、二重結合数3以上の脂肪酸であり、より好ましくは炭素数20以上、二重結合数3以上又は4以上の脂肪酸、特に好ましくは炭素数20以上、二重結合数5以上の脂肪酸である。具体的にはα‐リノレン酸(18:3,n‐3)、γ‐リノレン酸(18:3,n‐6)、ジホモ-γ-リノレン酸(20:3、n-6)、アラキドン酸(20:4,n‐6)、エイコサペンタエン酸(20:5,n‐3)、ドコサペンタエン酸(22:5,n‐6)、ドコサヘキサエン酸(22:6,n‐3)などが例示される。
これらはある種の微生物油、植物油や海産動物油などに多く含まれることが知られている。具体的には、イワシ油、マグロ油、カツオ油、メンヘイデン油、タラ肝油、ニシン油、カペリン油、およびサーモン油などの魚油やオキアミなどの甲殻類の海産動物油、エゴマ、アマ、大豆、菜種などの植物油、モルティエレラ(Mortierella)属、ペニシリューム(Penicillium)属、アスペルギルス(Aspergillus)属、ロードトルラ(Rhodotorula)属、フザリューム(Fusarium)属に属する微生物が産生する油脂などが例示される。
本発明の方法は、特にダイオキシン類による汚染が懸念される海産物由来の油脂、例えば、魚油、オキアミ油、又は海洋哺乳類油に適する。
本明細書において高度不飽和脂肪酸を構成脂肪酸として含有する油脂とはトリグリセリド、又はリン脂質を意味する。
これらの油脂を本発明の原料油として用いる場合、分子蒸留又は短行程蒸留に付す前に、前処理をしてもよい。このような前処理としては、脱ガム工程、活性白土や活性炭を用いた脱色工程、水洗工程などが例示される。
本発明においてダイオキシン類とは、表1に示した、ポリ塩化ジベンゾパラジオキシン(PCDD)、ポリ塩化ジベンゾフラン(PCDF)及びコプラナーPCB(Co-PCB)の合計を意味し、各成分の含有量を測定し、それぞれの実測値に毒性等量をかけて合計したて算出した毒性等量(pg-TEQ/g)で表した。
また、臭素化難燃剤についても測定した。臭素化難燃剤とは、表9に示すような化合物の総称である。環境中のダイオキシン類の汚染が低下し始めているのに対し、臭素化難燃剤についてはまだ増加傾向が見られており、注目すべき物質である。魚油中に比較的多く含まれるBDE-100、BDE-49、BDE-99、BDE-47などを指標とすることができる。
分子蒸留又は短行程蒸留は、被蒸留物が高温にさらされる時間が非常に短いので、熱に弱いEPA,DHA等を含有するトリグリセリドから不要成分を除去するのに適している。
このような条件で蒸留することにより、ダイオキシン類のうち、PCDD及びPCDFは測定限界未満、すなわち実質的に0にすることができた。ここで0とは例えば、表6検出限界の数値から計算すると0.043pg-TEQ/g未満であり、すなわち、0.05pg-TEQ/g未満にすることができる。コプラナーPCBも0.2pg-TEQ/g未満、さらに0.1 pg-TEQ/g未満、0.05 pg-TEQ/g未満、0.02 pg-TEQ/g未満、0.01pg-TEQ/g未満まで低下させることができる。
また、臭素化難燃剤では、BDE-100、BDE-49、BDE-99、BDE-47などを指標とすると、これらを0.05μg/g未満、好ましくは0.03μg/g未満、さらに0.02μg/g未満に低下させることができる。
原料油は水洗などの方法で脱ガム処理を施したものを用いるのが好ましい。水洗した原料油をそのまま上述の条件で分子蒸留又は短行程蒸留に付し、コレステロール、遊離脂肪酸、環境汚染物質などを留分として除去し、トリグリセリドを含む残留分を得る。この残留分はそのまま用いてもよいし、さらに活性炭、活性白土などによる脱色処理、水蒸気蒸留などによる脱臭処理をして用いることもできる。こうして製造した精製油脂は飼料、食品、サプリメントの成分として用いることができる。
残留分にエチルアルコールと触媒又は酵素を加え、反応させ、トリグリセリドの構成脂肪酸とエチルアルコールのエステルを生成させる。エチルエステル化は公知のどのような方法を用いてもかまわない。
エチルエステル化した後、必要に応じてさらに精製してもよい。EPAエチルエステルやDHAエチルエステルの純度を高めるためには、さらに分子蒸留、精留、カラムクロマトグラフィなどの方法を用いることができる。具体的には、特開平5-222392(ファミリーパテントEP0610506)、特開平4-41457(ファミリーパテントEP0460917)、特開平6-33088等に記載の方法で精製することができる。
精留は高真空下で3塔以上の蒸留塔により行い、EPAエチルエステル及び/又はDHAエチルエステルを主留として、より揮発性の高い初留及びより揮発性の低い残留と分離することにより得ることができる。精留の条件としては、温度は150~200℃、好ましくは160~190℃、さらに好ましくは170~190℃であり、圧力は1~300Pa、好ましくは1~200Pa、さらに好ましくは1~133Paである。1~133Paの真空度で、160~190℃、好ましくは170~190℃の主留を得るのが好ましい。
特に好ましいのは、精留後にカラムクロマトグラフィを行う方法である。本願発明者らは、精留によりEPAやDHAを濃縮すると、相対的にダイオキシン類の濃度が上昇するが、カラムクロマトグラフィを行うことにより、精留前のレベルよりも低下させることができることを見出した。カラムクロマトグラフィにはシリカゲル、イオン交換樹脂、活性白土、硝酸銀などを用いることができるが、逆相分配系のカラムクロマトグラフィが特に好ましい。逆相分配系を構成するように、たとえばアルキル基結合シリカ充填剤(ODSカラム等)等を用い、また、溶媒系としては、水、アルコール、ケトン類を用いることができる。好ましくはメタノールである。これらは単独、もしくは混合してもちいてもよい。
上述の精留、カラムクロマトグラフィを組み合わせることにより、高度不飽和脂肪酸を濃縮する一方で環境汚染物質の濃度を低下させることができる。高度不飽和脂肪酸、例えば、EPAエチルエステル及び/又はDHAエチルエステルの濃度を80面積%以上、85面積%以上、90面積%以上、95面積%以上さらに96面積%以上の純度に高め、かつ、ダイオキシン類のうち、PCDD及びPCDFは測定限界以下、すなわち、実質的に0(検出限界からの計算では0.043pg-TEQ/g未満)にすることができ、コプラナーPCBも0.1pg-TEQ/g未満、さらに0.03 pg-TEQ/g未満、0.01 pg-TEQ/g未満まで低下させることができる。あるいは、臭素化難燃剤では、BDE-47の量で0.18ng/g未満、BDE-100の量で0.03ng/g未満、BDE-49の量で0.05ng/g未満、又は、BDE-99の量で0.05ng/g未満に低下させることができる。BDE-100、BDE-49、BDE-99、BDE-47を0.05μg/g未満、好ましくは0.03μg/g未満、さらに0.02μg/g未満に低下させることができる。医薬品としては、EPAエチルエステル及び/又はDHAエチルエステルの濃度が96面積%以上の純度が好ましい。
これらのような高度不飽和脂肪酸の濃度が高く、環境汚染物質の濃度が低い遊離脂肪酸や脂肪酸エステルは、高度不飽和脂肪酸を有効成分とする医薬品やサプリメント原料に適する。
高度不飽和脂肪酸は上記の方法で製造した高度不飽和脂肪酸のエステルを加水分解して得ることができる。
ダイオキシン類、臭素化難燃剤の測定
本発明の実施例において、ダイオキシン類の測定は財団法人日本食品分析センターに依頼した。測定方法は、「食品のダイオキシン類の測定方法暫定ガイドライン(平成20年2月)」(平成11年衛食第138号、衛乳第200号)による。
臭素化難燃剤の測定は、食品等の分析会社であるeurofinsに依頼した。測定方法は高分解能質量分析法(HRGC/HRMS法)による。
本発明の実施例において、酸価(AV)の測定は基準油脂分析試験法(2003年度版)(社団法人日本油化学会編)に準じて行った。
原料に用いた魚油及び短行程蒸留による処理をした後の油の脂肪酸組成は、魚油をエチルエステル化してガスクロマトグラフィーにて測定した。すなわち、魚油40μLに1Nナトリウムエチラート/エタノール溶液1mLを加え、約30秒間撹拌した。その後、1N塩酸を1mL加えて中和し、ヘキサン2mL、飽和硫酸アンモニア水溶液3mLを加え、撹拌、静置後、上層をガスクロマトグラフィーにて測定した。
ガスクロマトグラフィー分析条件
機種;Agilent 6850 GC system (Agilent社)
カラム;DB-WAX J&W 123-7032E
カラム温度;200℃
注入温度 ;300℃
注入方法 ;スプリット
スプリット比;100:1
検出器温度:300℃
検出器:FID
キャリアーガス:ヘリウム
原料油と蒸留後のダイオキシン類濃度と酸価を表2に示した。
原料油の酸価の高低にかかわらず、また、原料油のダイオキシン類の含有量の多寡にかかわらず、いずれの条件でもダイオキシン類の含有量を0.1pg-TEQ/g以下に低下させることができた。
また、別の短行程蒸留装置(SPD) KD 6 (UIC GmbH社製、蒸留表面積0.06 m2)を用いてイワシ粗油からダイオキシン類の除去を行った。表3に示すとおり、この装置でも本発明の方法(蒸留温度を270℃、圧力0.6Pa、流速20(kg/hr)/m2)により、ダイオキシン類の含有量を0.1pg-TEQ/以下に低下させることができた。
原油と蒸留後(SPD油)の油中のダイオキシン類の測定結果をそれぞれ表5、6に示す。ダイオキシン類の総量を毒性等量で3.0pg-TEQ/gから0.014 pg-TEQ/gに低下させることができた。また、蒸留後の油の酸価は0.2以下であり、脂肪酸組成に変化はなかった。
製造方法は、SPDにより蒸留処理した油をアルカリ触媒下エチルアルコールとエタノリシス反応を行い、エチルエステルにした。温水で水洗した後、脱水し、精留(真空度13Pa、主留の温度約176℃)により主留を得、さらに逆相分配系(ODS)のカラムクロマトグラフィーを用いたHPLC処理し、溶剤を留去し、EPA純度97%のEPAエチルエステルを製造した。
このエチルエステルのダイオキシン類を実施例4と同様に測定した結果を表8に示す。エチルエステル化及びその後の精製行程でダイオキシン類が濃縮することはなく、実施例4の処理をした原料を用いることでダイオキシン類の総量が毒性等量で0.07pg-TEQ/g以下のEPAエチルエステルを製造することができた。表8は3つの異なるロットの原料を用いて実施した結果を示したものである。本発明の方法により、安定してダイオキシン類の総量が毒性等量で0.006~0.021pg-TEQ/gのEPAエチルエステルを製造することができることを確認した。測定限界以下のNDについて、測定限界の数値を挿入して計算しても、値として0.005上昇するだけであり、0.011~0.026 pg-TEQ/gのEPAエチルエステルを製造することができることを意味する。
原料油をアルカリ触媒によりエチルエステル化した。エチルエステルをまず精留工程にかけ、炭素数20の脂肪酸のエチルエステルを含む留分を採取した。続いて、ODSのカラムクロマトグラフィにより、エイコサペンタエン酸エチルエステルの画分を採取した。
それぞれの段階で、ダイオキシン類を測定した。
カラム処理により、#77は不変、あるいは、やや増加しているのに対し、他の成分は大きく低下した。カラム処理においては、エチルエステルとダイオキシン類が異なる挙動を示して、分離できたものと考えられる。
したがって、精留とカラム処理を組み合わせることによって、目的のエチルエステルを濃縮することとダイオキシン類を低減させることを同時に達成することができる。
Claims (20)
- 高度不飽和脂肪酸を構成脂肪酸として含有する油脂を原料油として製造され、環境汚染物質の含有量が低減された、高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルであって、含まれるダイオキシン類のうち、ポリ塩化ジベンゾパラジオキシン(PCDD)及びポリ塩化ジベンゾフラン(PCDF)の含有量が0.05pg-TEQ/g未満、コプラナーPCB(Co-PCB)が0.03pg-TEQ/g未満である、高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
- さらに、含まれる臭素化難燃剤の含有量がBDE-47の量が0.18ng/g未満、BDE-100の量が0.03ng/g未満、BDE-49の量が0.05ng/g未満、又は、BDE-99の量が0.05ng/g未満に低減されている請求項1の高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
- 脂肪酸中に占める高度不飽和脂肪酸の濃度が80面積%以上、85面積%以上、90面積%以上、95面積%以上、又は96面積%以上である、請求項1又は2の高度不飽和脂肪酸のエチルエステル。
- 高度不飽和脂肪酸を構成脂肪酸として含有する油脂が魚油、オキアミ油、海洋哺乳類油又は微生物油である請求項1ないし3いずれかの高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
- 高度不飽和脂肪酸がエイコサペンタエン酸、ドコサヘキサエン酸、ドコサペンタエン酸、ジホモ-γ-リノレン酸、アラキドン酸のいずれか、又はこれらの組み合わせである請求項1ないし4いずれかの高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
- 請求項1ないし5いずれかの高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルを有効成分として含有する医薬品、サプリメント又は食品。
- a) 高度不飽和脂肪酸を構成脂肪酸として含有する原料油から、薄膜蒸留により遊離脂肪酸及び環境汚染物質を除去し、
b) 得られた高度不飽和脂肪酸含有油脂を加水分解又はエチルエステル化し、
c) 精留及びカラムクロマトグラフィにより精製することにより、
ポリ塩化ジベンゾパラジオキシン(PCDD)、ポリ塩化ジベンゾフラン(PCDF)及びコプラナーPCB(Co-PCB)の含有量を低減させた高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルを製造する方法。 - さらに、臭素化難燃剤の含有量も低下させる請求項7の方法。
- 高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルの脂肪酸中に占める高度不飽和脂肪酸の濃度が80面積%以上、85面積%以上、90面積%以上、95面積%以上、又は96面積%以上である、請求項7又は8の方法。
- 高度不飽和脂肪酸を構成脂肪酸として含有する原料油が魚油、オキアミ油、海洋哺乳類油又は微生物油である請求項7ないし9いずれかの方法。
- 前記薄膜蒸留が、200~270℃、220~260℃、又は220~250℃の温度で実行される、請求項7ないし10いずれかの方法。
- 前記薄膜蒸留が、5Pa以下、2Pa、又は1Pa以下の圧力で実行される、請求項7ないし11いずれかの方法。
- 前記薄膜蒸留が、流速20~200(kg/h)/m2、又は25~120(kg/h)/m2で実行される、請求項7ないし12いずれかの方法。
- 前期薄膜蒸留が分子蒸留又は短行程蒸留である請求項7ないし13いずれかの方法。
- 精留が、3塔以上の蒸留塔にて行うものである請求項7ないし14のいずれかの方法。
- カラムクロマトグラフィによる精製が、逆相分配系のカラムクロマトグラフィを用いるものである請求項7ないし15のいずれかの方法。
- 請求項7ないし16いずれかの方法により製造された、ダイオキシン類の含有量が0.07pg-TEQ/g未満、又は0.05 pg-TEQ/g未満である、高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
- さらに、含まれる臭素化難燃剤の含有量がBDE-47の量が0.18ng/g未満、BDE-100の量が0.03ng/g未満、BDE-49の量が0.05ng/g未満、又は、BDE-99の量が0.05ng/g未満である請求項17の高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
- 脂肪酸中に占める高度不飽和脂肪酸の濃度が80面積%以上、85面積%以上、90面積%以上、95面積%以上、又は96面積%以上である請求項17又は18の高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステル。
- 請求項21ないし23いずれかの高度不飽和脂肪酸又は高度不飽和脂肪酸のエチルエステルを含有する医薬品、サプリメント、又は食品。
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