EP1841847A1 - Verfahren zur herstellung einer dha-haltigen fettsäure-zusammensetzung - Google Patents
Verfahren zur herstellung einer dha-haltigen fettsäure-zusammensetzungInfo
- Publication number
- EP1841847A1 EP1841847A1 EP06701343A EP06701343A EP1841847A1 EP 1841847 A1 EP1841847 A1 EP 1841847A1 EP 06701343 A EP06701343 A EP 06701343A EP 06701343 A EP06701343 A EP 06701343A EP 1841847 A1 EP1841847 A1 EP 1841847A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- fatty acid
- acid composition
- biomass
- equal
- esters
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 235000014113 dietary fatty acids Nutrition 0.000 title claims abstract description 145
- 239000000194 fatty acid Substances 0.000 title claims abstract description 145
- 229930195729 fatty acid Natural products 0.000 title claims abstract description 145
- 239000000203 mixture Substances 0.000 title claims abstract description 137
- 150000004665 fatty acids Chemical class 0.000 title claims abstract description 126
- 238000004519 manufacturing process Methods 0.000 title abstract description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 90
- 238000000034 method Methods 0.000 claims abstract description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 49
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 claims abstract description 49
- -1 saturated fatty acid ester Chemical class 0.000 claims abstract description 48
- 239000004202 carbamide Substances 0.000 claims abstract description 47
- 239000002028 Biomass Substances 0.000 claims abstract description 30
- 235000020669 docosahexaenoic acid Nutrition 0.000 claims abstract description 26
- 239000002244 precipitate Substances 0.000 claims abstract description 23
- 239000007788 liquid Substances 0.000 claims abstract description 22
- 239000003960 organic solvent Substances 0.000 claims abstract description 13
- 229940090949 docosahexaenoic acid Drugs 0.000 claims abstract description 10
- 229940053200 antiepileptics fatty acid derivative Drugs 0.000 claims abstract description 7
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 claims description 36
- 150000002148 esters Chemical class 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 22
- 238000005809 transesterification reaction Methods 0.000 claims description 20
- 241001298226 Ulkenia sp. Species 0.000 claims description 18
- 238000000605 extraction Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 8
- 150000002978 peroxides Chemical class 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 229910001385 heavy metal Inorganic materials 0.000 claims description 6
- 239000007791 liquid phase Substances 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
- 235000013373 food additive Nutrition 0.000 claims description 2
- 239000002778 food additive Substances 0.000 claims description 2
- 235000012041 food component Nutrition 0.000 claims description 2
- 239000005417 food ingredient Substances 0.000 claims description 2
- 125000005233 alkylalcohol group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 238000001816 cooling Methods 0.000 abstract description 4
- 125000005907 alkyl ester group Chemical group 0.000 abstract 2
- 239000000243 solution Substances 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 150000004702 methyl esters Chemical class 0.000 description 13
- 239000012454 non-polar solvent Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 235000021288 n-6 DPA Nutrition 0.000 description 5
- 235000003441 saturated fatty acids Nutrition 0.000 description 5
- 150000004671 saturated fatty acids Chemical class 0.000 description 5
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 5
- AVKOENOBFIYBSA-WMPRHZDHSA-N (4Z,7Z,10Z,13Z,16Z)-docosa-4,7,10,13,16-pentaenoic acid Chemical group CCCCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O AVKOENOBFIYBSA-WMPRHZDHSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 125000005456 glyceride group Chemical group 0.000 description 4
- 239000011261 inert gas Substances 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229910015900 BF3 Inorganic materials 0.000 description 3
- 241000598397 Schizochytrium sp. Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000007824 aliphatic compounds Chemical class 0.000 description 3
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000003495 polar organic solvent Substances 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- FLIACVVOZYBSBS-UHFFFAOYSA-N Methyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC FLIACVVOZYBSBS-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 2
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 2
- 229910052785 arsenic Inorganic materials 0.000 description 2
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 229910052793 cadmium Inorganic materials 0.000 description 2
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 2
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 2
- 235000004626 essential fatty acids Nutrition 0.000 description 2
- 239000010696 ester oil Substances 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 235000019387 fatty acid methyl ester Nutrition 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 229940013317 fish oils Drugs 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 229960004488 linolenic acid Drugs 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229910052756 noble gas Inorganic materials 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 2
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- YUFFSWGQGVEMMI-JLNKQSITSA-N (7Z,10Z,13Z,16Z,19Z)-docosapentaenoic acid Chemical class CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCCC(O)=O YUFFSWGQGVEMMI-JLNKQSITSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 235000021294 Docosapentaenoic acid Nutrition 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- DVSZKTAMJJTWFG-UHFFFAOYSA-N docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCCC=CC=CC=CC=CC=CC=CC(O)=O DVSZKTAMJJTWFG-UHFFFAOYSA-N 0.000 description 1
- MBMBGCFOFBJSGT-SFGLVEFQSA-N docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C\C\C=C\C\C=C\C\C=C\C\C=C\C\C=C\CCC(O)=O MBMBGCFOFBJSGT-SFGLVEFQSA-N 0.000 description 1
- VCDLWFYODNTQOT-UHFFFAOYSA-N docosahexaenoic acid methyl ester Natural products CCC=CCC=CCC=CCC=CCC=CCC=CCCC(=O)OC VCDLWFYODNTQOT-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000008524 evening primrose extract Nutrition 0.000 description 1
- 229940089020 evening primrose oil Drugs 0.000 description 1
- 239000010475 evening primrose oil Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 235000020664 gamma-linolenic acid Nutrition 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000199 molecular distillation Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002835 noble gases Chemical class 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 229940033080 omega-6 fatty acid Drugs 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000005325 percolation Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229940119224 salmon oil Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Classifications
-
- 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
- C11C1/00—Preparation of fatty acids from fats, fatty oils, or waxes; Refining the fatty acids
- C11C1/02—Preparation of fatty acids from fats, fatty oils, or waxes; Refining the fatty acids from fats or fatty oils
- C11C1/025—Preparation of fatty acids from fats, fatty oils, or waxes; Refining the fatty acids from fats or fatty oils by saponification and release of fatty acids
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS, COOKING OILS
- A23D9/00—Other edible oils or fats, e.g. shortenings, cooking oils
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
- C11B7/00—Separation of mixtures of fats or fatty oils into their constituents, e.g. saturated oils from unsaturated oils
- C11B7/0083—Separation of mixtures of fats or fatty oils into their constituents, e.g. saturated oils from unsaturated oils with addition of auxiliary substances, e.g. cristallisation promotors, filter aids, melting point depressors
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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
-
- 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
- C11C3/04—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom by esterification of fats or fatty oils
- C11C3/10—Ester interchange
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to a method for producing a fatty acid composition which contains, based on the total weight of the fatty acids contained in the fatty acid composition and / o "of the fatty acid derivatives at least 70.0 wt .-% docosahexaenoic acid and / or docosahexaenoic.
- PUFAs Highly unsaturated polyunsaturated fatty acids
- PUFAs are essential fatty acids in human metabolism.
- PUFAs can be divided into two large groups.
- ⁇ -6 PUFAs which is formulated starting from linoleic acid
- ⁇ -3 PUFAs which is built up from the ⁇ -linolenic acid.
- PUFAs are important building blocks of cell membranes, retina and meninges and precursors of important hormones such as prostaglandins, thromboxanes and leukotrienes.
- DHA docosahexaenoic acid
- precursor fatty acids precursors, eg ⁇ -linolenic acid
- the human is able to synthesize highly unsaturated fatty acids.
- this amount is sufficient to meet the need for high-unsaturated fatty acids is controversial.
- vegetable oils are enriched with ⁇ -6 fatty acids, (for example, evening primrose oil contains ⁇ -linolenic acid (GLA)), but only up to a chain length of Cl 8, and fish oils or oils from microorganisms with ⁇ -3 fatty acids (eg, salmon oil contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; all-cis 4,7,10,13,16,19 docosahexaenoic acid)).
- GLA ⁇ -linolenic acid
- fish oils or oils from microorganisms with ⁇ -3 fatty acids eg, salmon oil contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; all-cis 4,7,10,13,16,19 docosahexaenoic acid).
- fish oils and microorganism oils are the only commercial source of highly unsaturated fatty acids.
- the content of the desired PUFA is low and these are present in a mixture, and antagonistic PUFAs may also be included.
- antagonistic PUFAs may also be included.
- a high amount of oil must be taken.
- this applies to those patients who must take high doses of PUFAs (for example, in cystic fibrosis).
- enriched or high-purity PUFAs must be used. There is therefore a high demand for high-purity PUFAs in the prior art.
- WO 01/51598 A1 discloses a process for the preparation of an enriched mixture of polyunsaturated fatty acid esters, in which an oil of Schizochytrium sp. transesterified with an alcohol (methanol). The fatty acid esters are then dissolved together with urea in a medium and cooled or concentrated to at least partially separate the saturated fatty acid esters which precipitate together with the urea. In this way, an oil can be obtained which, according to gas chromatography, contains 23.4% by weight of ⁇ -6 DPA methyl ester, 65.2% by weight of ⁇ -3-DHA methyl ester, 2.9% by weight of myristic acid. Methyl ester and 1.5 wt .-% palmitic acid methyl ester.
- the process should provide a fatty acid composition with the highest possible purity and quality, in particular with the lowest possible acid value and / or with the lowest possible heavy metal content.
- the process should be as gentle as possible and in particular to fatty acid compositions with the lowest possible peroxide - lead.
- the process according to the invention should be possible as far as possible using solvents which are as suitable as possible for food.
- the use of hazardous substances should be avoided as far as possible.
- the fatty acid compositions obtainable by the process should have the lowest possible ethyl carbamate content, in particular the Application of fatty acid compositions in the food industry without hesitation.
- a fatty acid composition which, based on the total weight of the fatty acids and / or fatty acid derivatives present in the fatty acid composition, contains at least 70.0% by weight of all-cis 4,7,10, 13,16,19 docosahexaenoic acid and / or allcis 4,7,10,13,16,19 docosahexaenoic acid alkyl ester, wherein: a) one from Ulkenia sp.
- transesterifying available biomass with at least one alcohol to form at least one docosahexaenoic acid alkyl ester and at least one saturated fatty acid ester b) preparing a solution containing urea, at least part of the transesterified biomass from step a) and at least one organic solvent, c ) cooling or concentrating the solution of step b) to i) a precipitate containing urea and at least a portion of the saturated fatty acid esters, and ii) forming a liquid fraction, d) the precipitate i) of the liquid fraction ii) disconnects, fails to provide a novel and useful process for preparing a fatty acid composition which, based on the total weight of the fatty acids and / or fatty acid derivatives present in the fatty acid composition, is at least 70.0 wt.
- the method according to the invention can be carried out in a simple manner, on an industrial scale and at low cost. > The inventive method is extremely efficient and makes the
- the process according to the invention provides a fatty acid composition with comparatively high purity and quality, in particular with a comparatively low acid number and with a comparatively low heavy metal content.
- the acid number of the fatty acid composition is preferably less than or equal to 1.5 mg KOH per g of fatty acid composition, desirably less than or equal to 0.8 mg KOH per g of fatty acid composition, preferably smaller or equal to 0.2 mg KOH per g fatty acid composition, in particular less than or equal to 0.06 mg KOH per g fatty acid composition.
- the process according to the invention is comparatively gentle and leads to fatty acid compositions with a comparatively low peroxide content.
- the peroxide value of the fatty acid composition measured according to AOCS Official Method Cd-3d 63, is preferably less than or equal to 0.5 meq. per kg of fatty acid composition, suitably less than or equal to 0.1 meq. per kg of fatty acid composition, preferably less than or equal to 0.05 meq. per kg of fatty acid composition, in particular less than or equal to 0.01 meq. per kg fatty acid composition.
- the heavy metal content of the fatty acid composition is preferably less than or equal to 0.7 mg per kg fatty acid composition, advantageously less than or equal to 0.4 mg per kg fatty acid composition, preferably smaller or equal to 0.3 mg per kg of fatty acid composition, in particular less than or equal to 0.2 mg per kg of fatty acid composition.
- the fatty acid compositions obtainable by the process are distinguished by a comparatively low cadmium content.
- the cadmium content of the fatty acid compositions obtainable according to the invention, measured in accordance with LMBG ⁇ 35 L06.00-7, is preferably less than or equal to 0.20 mg per kg of fatty acid
- Composition suitably less than or equal to 0.10 mg per kg of fatty acid composition, preferably less than or equal to 0.05 mg per kg of fatty acid composition, in particular less than or equal to 0.03 mg per kg of fatty acid composition.
- the fatty acid compositions obtainable by the process are characterized by a comparatively low lead content.
- the lead content of the fatty acid compositions obtainable according to the invention, measured in accordance with LMBG ⁇ 35 L06.00-7, is preferably less than or equal to 0.20 mg per kg fatty acid composition, advantageously less than or equal to 0.10 mg per kg fatty acid composition , preferably less than or equal to 0.05 mg per kg fatty acid composition, in particular less than or equal to 0.03 mg per kg fatty acid composition.
- the fatty acid compositions obtainable by the process are characterized by a comparatively low mercury content.
- the mercury content of the fatty acid compositions obtainable according to the invention, measured according to LMBG ⁇ 35 L06.00-7, is preferably less than or equal to 0.10 mg per kg fatty acid composition, suitably less than or equal to 0.05 mg per kg fatty acid composition, preferably less than or equal to 0.01 mg per kg fatty acid composition, in particular less than or equal to 0.005 mg per kg fatty acid composition.
- the fatty acid compositions obtainable by the process are distinguished by a comparatively low arsenic content.
- the arsenic content of the fatty acid compositions obtainable according to the invention, measured in accordance with LMBG ⁇ 35 L06.00-7, is preferably less than or equal to 0.20 mg per kg of fatty acid
- Composition suitably less than or equal to 0.10 mg per kg of fatty acid composition, preferably less than or equal to 0.05 mg per kg of fatty acid composition, in particular less than or equal to 0.03 ⁇ mg per kg of fatty acid composition.
- the fatty acid compositions obtainable by the process are characterized by a comparatively low copper content.
- the copper content of the fatty acid compositions obtainable according to the invention, measured according to LMBG ⁇ 35 L06.00-7, is preferably less than or equal to 0.25 mg per kg fatty acid composition, advantageously less than or equal to 0.20 mg per kg fatty acid composition , preferably less than or equal to 0.10 mg per kg of fatty acid composition, in particular less than or equal to 0.06 mg per kg of fatty acid composition.
- r> obtainable by the process of fatty acid compositions are characterized content of iron by a comparatively low.
- the iron content of the fatty acid compositions obtainable according to the invention, measured in accordance with LMBG ⁇ 35 L06.00-7, is preferably less than or equal to 0.25 mg per kg fatty acid composition, advantageously less than or equal to 0.20 mg per kg fatty acid composition , preferably less than or equal to 0.10 mg per kg of fatty acid composition, in particular less than or equal to 0.06 mg per kg of fatty acid composition.
- the fatty acid compositions obtainable by the process are characterized by a comparatively low nickel content.
- the nickel content of the fatty acid compositions obtainable according to the invention, measured according to LMBG ⁇ 35 L06.00-7, is preferably less than or equal to 0.25 mg per kg fatty acid
- Composition expediently less than or equal to 0.20 mg per kg of fatty acid composition, preferably less than or equal to 0.10 mg per kg of fatty acid composition, in particular less than or equal to 0.06 mg per kg of fatty acid composition.
- comparatively food-safe solvents are used.
- the fatty acid compositions obtainable by the process according to the invention furthermore have a comparatively low ethylcarbamate content and are therefore particularly suitable for applications in the foodstuffs sector.
- the present invention relates to a process for preparing a fatty acid composition which, based on the total weight of the fatty acids and / or fatty acid derivatives present in the fatty acid composition, preferably based on the total weight of the fatty acids and / or fatty acid esters contained in the fatty acid composition, in particular based on the total weight of the fatty acids and / or fatty acid triglycerides contained in the fatty acid composition, at least 70.0% by weight of all-cis 4,7,10,13,16,19 docosahexaenoic acid and / or all-cis 4,7, 10,13,16,19 docosahexaenoic acid alkyl ester.
- fatty acid composition in this context includes both compositions containing free fatty acids and compositions containing fatty acid derivatives, preferably fatty acid esters, especially fatty acid triglycerides, wherein the fatty acid residues may in principle be the same or different.
- fatty acids denote aliphatic carboxylic acids which may be saturated or mono- or polyunsaturated and preferably have from 6 to 30 carbon atoms.
- Biomass used as starting material From Ulkenia sp. Available biomasses are known per se. According to the invention, both biomasses of Ulkenia sp. Wild-type strains as well as biomass of mutant or recombinant Ulkenia sp. Strains that efficiently produce DHA (all-cis 4,7,10,13,16,19 docosahexaenoic acid) and / or DPA (all-cis 4,7,10,13,16 docosapentaenoic acid). Such mutant or recombinant strains include microorganisms which, compared to the percentage of the original Ulkenia sp.
- Wild-type strain using the same substrate, a higher percentage of DHA and / or DPA in fats and / or compared to that obtained by the original Ulkenia sp. Wild-type strain, using the same substrate, containing a higher total amount of lipids.
- a Ulkenia sp. Dry mass used as starting material.
- an oil from Ulkenia sp. used as starting material.
- Oils from Ulkenia sp. are conveniently obtained by cultivating the microorganism rich in DHA, harvesting the biomass from the culture, digesting and isolating the oil.
- a very particularly favorable method in this context is described in WO 03/033631 A1, the disclosure of which is hereby incorporated by reference.
- Extractions with organic solvents are described inter alia in WO 9737032, in WO 9743362 and EP 515460. A particularly detailed presentation can also be found in the Journal of Dispersion Science and Technology, 10, 561-579, 1989 "Biotechnological. Processes for the Production of PUFAs".
- the extraction can also be carried out without solvent.
- a particularly favorable process in this context is described in EP-A-1178118. In this process, a solvent is avoided by preparing an aqueous suspension of the biomass and separating the oil phase from the aqueous phase by centrifugation.
- the composition of Ulkenia sp. Biomass available can vary widely.
- it contains at least one glyceride, in particular a triglyceride, which comprises at least one polyunsaturated fatty acid radical.
- at least 10%, more preferably at least 25% and especially at least 30% of the fatty acid residues in the biomass are DHA residues.
- a “glyceride”, as used herein, is an ester of glycerin and at least one fatty acid wherein one to three hydroxyl groups of the glycerol have been esterified with one or more fatty acid residues Radicals may be the same or different.
- Triglycerides ie esters of three fatty acid residues and glycerine.
- Each fatty acid residue may be either saturated (ie all bonds between the carbon atoms are single bonds) or unsaturated (ie there is at least one carbon-carbon double or triple bond).
- the nature of the unsaturated fatty acid residues are sometimes characterized herein with a ⁇ . This number indicates the position of the first double bond, when counting from the terminal methyl group of the fatty acid or fatty acid residue.
- the transesterification step is to cleave the fatty acid residues from the glycerol backbone of the glycerides in the starting material and form separate esters from each of the residues (at least one docosahexaenoic acid alkyl ester and at least one saturated fatty acid ester) such that the esters are separated can be.
- the transesterification is preferably carried out using at least one alcohol of the formula R 1 -OH, where R 1 is a linear or branched alkyl radical having 1 to 20, preferably 1 to 6, in particular 1 to 4, carbon atoms. Particularly preferred are the methyl esters and ethyl esters, especially the ethyl esters.
- the transesterification is catalyzed by at least one base.
- bases include sodium methoxide, potassium methoxide, elemental sodium, sodium hydroxide and potassium hydroxide.
- the volume ratio of the biomass to the base / alcohol mixture is 1: 1 to 1: 5.
- the concentration of the base in the alcohol is preferably 0.1 to 2 M.
- the transesterification reaction is carried out at room temperature (ie at a temperature in the range of about 20-25 ° C.) for 6-20 hours.
- the transesterification reaction at a temperature above room temperature, preferably at a temperature of at least 40 0 C, more preferably at a temperature of 70 to 150 0 C, in particular at a temperature above the boiling point of one or more components in the Mixture (under reflux), carried out.
- the transesterification is catalyzed by at least one acid, preferably by the biomass at a temperature of about 0 to about 15O 0 C in a mixture which incubates the at least one alcohol and at least one acid, preferably HCl, preferably under an inert gas atmosphere and in the absence of water.
- the triglyceride / acid / alcohol mixture is refluxed for at least 2 hours.
- the triglyceride / acid / alcohol mixture is maintained at a temperature of 0 to 5O 0 C for at least 12 hours.
- the triglyceride concentration in the alcohol / acid mixture is 0.1 to 15% by weight.
- the concentration of the acid, preferably HCl, in the alcohol / acid mixture is preferably 4 to 15% by weight.
- Such a mixture can be prepared by many different methods known in the art, such as, for example, by introducing gaseous hydrogen chloride into dry alcohol or by adding acetyl chloride to alcohol.
- HCl is most preferred in the present invention, other acids may alternatively be used.
- Such an acid is H 2 SO 4 , which is preferably used at a concentration of 0.5 to 5% by weight in the alcohol.
- H 2 SO 4 is a strong oxidizing agent, and therefore preferably only in combination with short reflux times (ie, less than 6 hours), low concentrations (ie, less than 5 wt%), and low temperatures (ie, less 15O 0 C) is used.
- boron fluoride which is preferably used at a concentration of 1-20% by weight.
- HCl is preferred over boron fluoride because boron fluoride is more prone to form undesired by-products.
- the transesterification reaction is preferably carried out under an inert gas atmosphere (eg noble gas and / or N 2 ). Furthermore, an antioxidant (eg Ascorbyl palmitate or propyl galate) may be added to the reaction mixture to prevent autooxidation.
- an antioxidant eg Ascorbyl palmitate or propyl galate
- At least one organic solvent is preferably added.
- preferred solvents include those compounds which are capable of dissolving the fatty acid esters to be transesterified.
- the organic solvent is preferably capable of dissolving all the fatty acid esters to be transesterified.
- Very particularly suitable solvents according to the invention include dichloromethane, acetonitrile, ethyl acetate and diethyl ether, in particular dichloromethane.
- the esters are preferably separated from the reaction mixture by addition of water. Often, the esters (which are organic) float on top of the reaction mixture and can easily be separated from the remaining reaction mixture. This is especially true for large-scale, industrial applications.
- a liquid-liquid solvent extraction can be used to separate the esters from the remaining reaction mixture.
- This extraction can vary within a wide range.
- water is added to the mixture and the esters are extracted with a non-polar solvent. If the transesterification has been catalyzed by at least one base, the water preferably comprises a sufficient amount of acid, preferably HCl, citric acid or acetic acid, especially HCl, to neutralize the mixture or more preferably to give the mixture a weakly acidic pH.
- the ratio of the total volume of the non-polar solvent to the volume of the reaction mass (including the added water) can also be varied within a wide range, and is more preferably from 1: 3 to 4: 3.
- the mixture is extracted with several fractions of the non-polar organic solvent, which are finally combined.
- Particularly suitable non-polar solvents according to the present invention include petroleum ether, pentane, hexane, cyclohexane and heptane, with hexane and petroleum ether being most preferred.
- the non-polar solvent may also contain a small amount of a weakly polar organic solvent, such as diethyl ether.
- a weakly polar organic solvent such as diethyl ether.
- the volumetric concentration of the weakly polar component to the nonpolar component is preferably not greater than about 20%, more preferably not greater than 10%, and most preferably from 5% to 10%.
- the resulting organic extraction solvent layer may be washed to remove, for example, any acid residues and / or remaining water.
- the removal of acid residues is preferably accomplished by washing the layer with an aqueous solution containing a weak base, e.g. For example, potassium carbonate.
- Remaining water removal can be achieved, for example, by washing the layer with a brine (i.e., a saturated brine) and / or by drying with an anhydrous salt (e.g., sodium sulfate or magnesium sulfate).
- the fatty acid esters can be concentrated in the non-polar solvent layer. According to a preferred embodiment, the fatty acid esters can be concentrated in the non-polar solvent layer. According to a preferred
- the esters are concentrated by evaporating a portion of the non-polar solvent.
- the transesterification of a from Ulkenia sp. Biomass available in addition to the DHA alkyl ester usually provides other fatty acid esters. Many of these fatty acid esters, especially the saturated fatty acid esters, have unknown and / or adverse medical properties and nutritional properties. It is therefore necessary, as completely as possible to remove the saturated fatty acid esters from the transesterification reaction mixture.
- the process according to the invention therefore comprises a urea crystallization in which b) first produces a solution containing urea, at least part of the transesterified biomass from step a) and at least one organic solvent, c) cooling the solution from step b) or concentrated to i) a precipitate containing urea and at least a portion of the saturated fatty acid esters, and ii) forming a liquid fraction, d) separating the precipitate i) from the liquid fraction ii).
- urea crystallizes in a solution containing polyunsaturated fatty acid esters (eg, esters of DHA) and saturated fatty acid esters obtained by transesterification using the method described above
- a precipitate forms which comprises the urea and at least a portion thereof containing the saturated fatty acid ester.
- this precipitate comprises a much lower proportion of polyunsaturated fatty acid esters than the starting solution. The majority of polyunsaturated fatty acid esters therefore remain in solution and can be easily separated from the precipitated saturated fatty acid esters.
- the urea crystallization separation process of the present invention comprises first forming a solution containing the fatty acid esters and urea.
- the amount of urea is preferably proportional to the
- Urea is preferably 1: 1 to 1: 4.
- the solution also preferably comprises at least one organic solvent which dissolves urea and the desired DHA ester, more preferably urea and all fatty acid esters in the mixture.
- particularly suitable solvents include alcohols having 1 to 4 carbon atoms, with methanol and ethanol, especially ethanol, being particularly preferred.
- the volumetric ratio of the mixture of the fatty acid esters to the solvent is preferably 1: 5 to 1:20.
- substantially all of the urea is dissolved in the solution.
- This can generally be achieved by heating the solution, preferably to a temperature of greater than 50.degree.
- the solution is prepared by dissolving the urea and the fatty acid ester mixture from each other, preferably, dissolved separately under heating, particularly at temperatures greater than 5O 0 C in the solvent and the resulting solutions then mixed together ,
- the solution containing the fatty acid esters and the urea is preferably cooled to form a precipitate comprising urea.
- the solution is cooled to a temperature of less than 40 ° C, preferably less than or equal to 30 0 C, in particular less than or equal to 25 ° C, the temperature conveniently greater than 10 0 C, preferably greater than or equal to 15 0 C, suitably greater or equal to 20 ° C, is.
- the cooled solution is preferably allowed to stand for a certain period of time, typically not longer than about 20 hours, preferably for 5 to 20 hours, at the cooled temperature with occasional stirring.
- a urea-containing precipitate is formed by concentrating the solution containing the fatty acid esters and the urea.
- the solution can be concentrated by adding a portion of the solvent evaporated in the solution.
- the amount of solvent removed is preferably sufficient to effect a urea concentration in the solution that exceeds the saturation concentration.
- the urea crystallization is conveniently carried out under an inert gas atmosphere (eg noble gases and / or N 2 )
- the precipitate is preferably separated from the liquid fraction enriched with polyunsaturated esters. This is preferably achieved by filtration or centrifugation. According to a particularly preferred embodiment, the precipitate is then (preferably saturated with urea) with a small amount of the organic solvent washed 'by adhering to the precipitate, polyunsaturated recover fatty acid esters. This washing solution is in turn preferably combined with the liquid fraction.
- the liquid fraction is preferably concentrated, combined with water, and the esters contained in the liquid fraction are preferably extracted with a non-polar solvent.
- the liquid fraction may be concentrated by vaporizing a portion of the solvent from the liquid fraction, wherein the vaporized amount of the solvent is preferably not so large that further urea precipitates.
- the amount of water added to the concentrated liquid fraction may vary within a wide range. Preferably that is
- volume ratio of water to the concentrated liquid fraction 4 1 to 1: 1.
- a sufficient amount of acid is also added to neutralize the urea.
- Particularly suitable nonpolar solvents for the purposes of the present invention include petroleum ether, pentane, hexane, cyclohexane, Ethyl acetate and heptane, with hexane being most preferred.
- the volumetric ratio of the nonpolar solvent to the concentrated liquid fraction / water mixture is preferably 1: 5 to 5: 1.
- the liquid fraction is also extracted with a weakly polar organic solvent to maximize the recovery of the fatty acid esters (which, as noted previously, are weakly polar).
- a weakly polar organic solvent particularly useful in the present invention include diethyl ether and ethyl acetate, with diethyl ether being most preferred.
- the volumetric ratio of the weakly polar solvent to the concentrated liquid fraction / water mixture is 1: 5 to 5: 1.
- the extracts may be dried by, for example, washing with a brine and / or using an anhydrous salt (e.g., sodium sulfate).
- an anhydrous salt e.g., sodium sulfate
- the solution is then preferably concentrated, for example by partial or complete evaporation of the solvent.
- the inventive method is characterized in particular by an extremely efficient separation of the saturated fatty acid esters. Therefore, in the context of the present invention, the transesterified biomass is preferably directly, i. without further intermediate steps, subjected to urea crystallization.
- nonpolar solvents as described above, as well as winterization, have proven particularly useful.
- Winterization involves cooling a solution containing the transesterified biomass to a temperature which causes at least a portion of the saturated fatty acid ester to precipitate, while a much lower proportion of the polyunsaturated fatty acid ester precipitates.
- the solution is at a temperature less, more preferably to a temperature in the range -30 to -10 0 C, in particular to a temperature in the range of -25 to -15 ° C, cooled 0 ° C.
- the solution is preferably maintained at these temperatures for up to 20 hours and under an inert gas atmosphere.
- the winterization is preferably carried out in an organic solvent which dissolves the DHA ester and at least one saturated fatty acid ester in the fatty acid ester mixture.
- organic solvents include methanol and ethanol, with methanol being most preferred.
- the volumetric ratio of the fatty acid ester mixture to the organic solvent is 1: 5 to 1:20.
- the solution is preferably separated from the precipitate to form a liquid fraction enriched in the desired polyunsaturated fatty acid esters. This is preferably achieved by filtration or centrifugation. After the liquid fraction is separated, it is conveniently concentrated by evaporation of the solvent in a rotary evaporator.
- the fatty acid compositions obtainable according to the invention are immediately obvious to the person skilled in the art. They are particularly suitable for all applications that are pre-defined for PUFAs and PUFA esters.
- the fatty acid compositions according to the invention can usually be used directly.
- fatty acid compositions obtainable according to the invention are used in particular as an active ingredient or component in pharmaceutical fatty acid compositions, as a constituent in cosmetic preparations, as a food additive or food ingredient, as a component of functional foods and for the production of higher-concentration PUFA derivatives, such as esters and acids.
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102005003625A DE102005003625A1 (de) | 2005-01-26 | 2005-01-26 | Verfahren zur Herstellung einer DHA-haltigen Fettsäure-Zusammensetzung |
PCT/EP2006/000677 WO2006079534A1 (de) | 2005-01-26 | 2006-01-26 | Verfahren zur herstellung einer dha-haltigen fettsäure-zusammensetzung |
Publications (1)
Publication Number | Publication Date |
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EP1841847A1 true EP1841847A1 (de) | 2007-10-10 |
Family
ID=36088309
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP06701343A Withdrawn EP1841847A1 (de) | 2005-01-26 | 2006-01-26 | Verfahren zur herstellung einer dha-haltigen fettsäure-zusammensetzung |
Country Status (9)
Country | Link |
---|---|
US (1) | US20080175975A1 (ko) |
EP (1) | EP1841847A1 (ko) |
JP (2) | JP2008528743A (ko) |
KR (1) | KR100990814B1 (ko) |
CN (1) | CN101107348A (ko) |
AU (1) | AU2006208643A1 (ko) |
CA (1) | CA2595917C (ko) |
DE (1) | DE102005003625A1 (ko) |
WO (1) | WO2006079534A1 (ko) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101262863B (zh) * | 2005-07-08 | 2016-08-31 | Dsmip资产公司 | 用于治疗痴呆和前痴呆相关病症的多不饱和脂肪酸 |
US8003813B2 (en) | 2006-06-27 | 2011-08-23 | Pos Pilot Plant Corporation | Process for separating saturated and unsaturated fatty acids |
WO2010004784A1 (ja) * | 2008-07-10 | 2010-01-14 | 株式会社J-オイルミルズ | 飲食品の呈味向上剤 |
US8815570B2 (en) | 2008-10-02 | 2014-08-26 | Feyecon B.V. | Microalgae extract containing omega 3-polyunsaturated fatty acids and method for extracting oil from micro-organisms |
CA2752562A1 (en) | 2008-12-08 | 2010-07-08 | Initio Fuels Llc | Single step transesterification of feedstock using a gaseous catalyst |
MX356532B (es) * | 2009-03-19 | 2018-06-01 | Martek Biosciences Corp | Traustoquitridos, composiciones de acidos grasos y metodos de produccion y uso de los mismos. |
CN101940238B (zh) * | 2010-08-13 | 2013-09-11 | 广东润科生物工程有限公司 | 一种营养保健食用油及其制备方法和其包装结构 |
EP2734626B1 (en) * | 2011-07-21 | 2020-12-16 | DSM IP Assets B.V. | Microbial oils enriched in polyunsaturated fatty acids |
FR3005860B1 (fr) * | 2013-05-21 | 2016-01-22 | Oreal | Compositions comprenant de l'huile d'ulkenia et leurs utilisations pour ameliorer et/ou renforcer la fonction barriere |
SG10201912618XA (en) * | 2015-08-31 | 2020-02-27 | Nippon Suisan Kaisha Ltd | Free polyunsaturated fatty acid-containing composition and manufacturing method therefor |
CN107529783A (zh) * | 2015-10-01 | 2018-01-02 | 帝斯曼知识产权资产管理有限公司 | 用于宠物食品中的补充物质 |
MX2018004128A (es) * | 2015-10-05 | 2018-05-17 | Dsm Ip Assets Bv | Composiciones de aceite y metodos para elaborarlas. |
JP6938163B2 (ja) * | 2017-02-06 | 2021-09-22 | 長瀬産業株式会社 | 脂質組成物、その用途及びその製造方法 |
KR101976468B1 (ko) * | 2017-11-30 | 2019-05-10 | 주식회사이맥솔루션 | 요소수 점적 결정법을 이용한 고산가 유지 폐자원 활용 고순도 불포화 지방산 메틸 에스테르의 제조방법 |
EP3586640A1 (en) | 2018-06-21 | 2020-01-01 | Nuseed Pty Ltd | Dha enriched polyunsaturated fatty acid compositions |
KR102216753B1 (ko) * | 2018-11-27 | 2021-02-17 | 주식회사이맥솔루션 | 팜유 또는 동물성 폐유지를 이용한 고순도 불포화 지방산 메틸 에스테르 제조방법 |
IL293602A (en) * | 2019-12-05 | 2022-08-01 | Vaxa Tech Ltd | Nutritional supplement for animals and aquaculture and a method for its preparation |
IL294990A (en) * | 2020-01-30 | 2022-09-01 | Silicycle Inc | A process for preparing a solid form of basic amino acid salts of polyunsaturated fatty acids |
CN113584093B (zh) * | 2021-07-30 | 2022-07-19 | 江南大学 | 一种高dha含量的结构脂质的制备方法及其产品 |
Family Cites Families (9)
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US4792418A (en) * | 1985-08-14 | 1988-12-20 | Century Laboratories, Inc. | Method of extraction and purification of polyunsaturated fatty acids from natural sources |
GB2218984B (en) * | 1988-05-27 | 1992-09-23 | Renafield Limited | Process for preparing high-concentration mixtures of polyunsaturated fatty acids & their esters and their prophylactic or therapeutic uses |
DE69417726T2 (de) * | 1994-05-09 | 1999-08-19 | Societe Des Produits Nestle S.A. | Verfahren zur Herstellung eines Konzentrates von Estern von mehrfach ungesättigten Fettsäuren |
DE69637953D1 (de) * | 1995-04-17 | 2009-07-30 | Nat Inst Of Advanced Ind Scien | Hoch ungesättigte fettsäurenproduzierende mikroorganismen und verfahren zur herstellung von hoch ungesättigten fettsäuren durch verwendung dieser mikroorganismen |
JP2764572B2 (ja) * | 1995-04-17 | 1998-06-11 | 工業技術院長 | ドコサヘキサエン酸生産能を有する新規微生物及びそれを用いたドコサヘキサエン酸の製造方法 |
ATE469244T1 (de) * | 1996-07-23 | 2010-06-15 | Nagase Chemtex Corp | Verfahren zur herstellung von docosahexansäure und docosapentansäure |
JP2000044982A (ja) * | 1998-07-27 | 2000-02-15 | Tama Seikagaku Kk | 不飽和脂肪酸アルキルエステルの濃縮分離方法 |
AU2001232786A1 (en) * | 2000-01-11 | 2001-07-24 | Monsanto Company | Process for making an enriched mixture of polyunsaturated fatty acid esters |
EP1178103A1 (en) * | 2000-08-02 | 2002-02-06 | Dsm N.V. | Purifying crude pufa oils |
-
2005
- 2005-01-26 DE DE102005003625A patent/DE102005003625A1/de not_active Ceased
-
2006
- 2006-01-26 WO PCT/EP2006/000677 patent/WO2006079534A1/de active Application Filing
- 2006-01-26 CA CA2595917A patent/CA2595917C/en not_active Expired - Fee Related
- 2006-01-26 JP JP2007552574A patent/JP2008528743A/ja active Pending
- 2006-01-26 CN CNA2006800031022A patent/CN101107348A/zh active Pending
- 2006-01-26 US US11/814,291 patent/US20080175975A1/en not_active Abandoned
- 2006-01-26 KR KR1020077017787A patent/KR100990814B1/ko not_active IP Right Cessation
- 2006-01-26 AU AU2006208643A patent/AU2006208643A1/en not_active Abandoned
- 2006-01-26 EP EP06701343A patent/EP1841847A1/de not_active Withdrawn
-
2013
- 2013-03-05 JP JP2013042692A patent/JP2013151689A/ja active Pending
Non-Patent Citations (1)
Title |
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See references of WO2006079534A1 * |
Also Published As
Publication number | Publication date |
---|---|
US20080175975A1 (en) | 2008-07-24 |
CA2595917C (en) | 2011-09-13 |
AU2006208643A1 (en) | 2006-08-03 |
KR20070094951A (ko) | 2007-09-27 |
JP2013151689A (ja) | 2013-08-08 |
JP2008528743A (ja) | 2008-07-31 |
KR100990814B1 (ko) | 2010-10-29 |
CA2595917A1 (en) | 2006-08-03 |
CN101107348A (zh) | 2008-01-16 |
WO2006079534A1 (de) | 2006-08-03 |
DE102005003625A1 (de) | 2006-07-27 |
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