WO2021156385A1 - Lipid composition comprising omega-3 fatty acids - Google Patents
Lipid composition comprising omega-3 fatty acids Download PDFInfo
- Publication number
- WO2021156385A1 WO2021156385A1 PCT/EP2021/052702 EP2021052702W WO2021156385A1 WO 2021156385 A1 WO2021156385 A1 WO 2021156385A1 EP 2021052702 W EP2021052702 W EP 2021052702W WO 2021156385 A1 WO2021156385 A1 WO 2021156385A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lipid composition
- fatty acid
- ethyl esters
- acid ethyl
- composition
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 160
- 150000002632 lipids Chemical class 0.000 title claims abstract description 109
- 235000020660 omega-3 fatty acid Nutrition 0.000 title claims abstract description 28
- 239000006014 omega-3 oil Substances 0.000 title claims abstract description 28
- 229940012843 omega-3 fatty acid Drugs 0.000 title claims abstract description 24
- 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 91
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims abstract description 52
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims abstract description 51
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims abstract description 51
- 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 claims abstract description 49
- 235000020669 docosahexaenoic acid Nutrition 0.000 claims abstract description 48
- 229940090949 docosahexaenoic acid Drugs 0.000 claims abstract description 45
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 41
- 235000010445 lecithin Nutrition 0.000 claims abstract description 41
- 239000000787 lecithin Substances 0.000 claims abstract description 41
- 229940067606 lecithin Drugs 0.000 claims abstract description 41
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 39
- 229930195729 fatty acid Natural products 0.000 claims abstract description 39
- 239000000194 fatty acid Substances 0.000 claims abstract description 39
- 150000002327 glycerophospholipids Chemical class 0.000 claims abstract description 33
- 125000005456 glyceride group Chemical group 0.000 claims abstract description 18
- 150000003626 triacylglycerols Chemical class 0.000 claims abstract description 14
- 125000004494 ethyl ester group Chemical group 0.000 claims abstract description 10
- 229930186217 Glycolipid Natural products 0.000 claims abstract description 7
- 239000003921 oil Substances 0.000 claims description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
- 239000002775 capsule Substances 0.000 claims description 23
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 20
- 150000004665 fatty acids Chemical group 0.000 claims description 18
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical group CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 16
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 13
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 claims description 8
- 229920000064 Ethyl eicosapentaenoic acid Polymers 0.000 claims description 7
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- 108010025899 gelatin film Proteins 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- TYLNXKAVUJJPMU-UHFFFAOYSA-N ethyl docosa-2,4,6,8,10,12-hexaenoate Chemical class CCCCCCCCCC=CC=CC=CC=CC=CC=CC(=O)OCC TYLNXKAVUJJPMU-UHFFFAOYSA-N 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 229940116333 ethyl lactate Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 3
- 206010013774 Dry eye Diseases 0.000 claims description 3
- 208000001344 Macular Edema Diseases 0.000 claims description 3
- 206010025415 Macular oedema Diseases 0.000 claims description 3
- 206010065062 Meibomian gland dysfunction Diseases 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 241000233671 Schizochytrium Species 0.000 claims description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 201000010230 macular retinal edema Diseases 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 230000009529 traumatic brain injury Effects 0.000 claims description 3
- 241000195649 Chlorella <Chlorellales> Species 0.000 claims description 2
- 241001501885 Isochrysis Species 0.000 claims description 2
- 241000196305 Nannochloris Species 0.000 claims description 2
- 241000224474 Nannochloropsis Species 0.000 claims description 2
- 235000019198 oils Nutrition 0.000 description 54
- 241000195493 Cryptophyta Species 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 150000003904 phospholipids Chemical class 0.000 description 12
- 240000002791 Brassica napus Species 0.000 description 11
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 11
- 229940106134 krill oil Drugs 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 description 8
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 8
- 235000013793 astaxanthin Nutrition 0.000 description 8
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 description 8
- 239000001168 astaxanthin Substances 0.000 description 8
- 229940022405 astaxanthin Drugs 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 238000005191 phase separation Methods 0.000 description 8
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 8
- 238000005809 transesterification reaction Methods 0.000 description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 8
- -1 diglycerides Chemical class 0.000 description 7
- 229960004488 linolenic acid Drugs 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000239366 Euphausiacea Species 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 235000010980 cellulose Nutrition 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 150000003905 phosphatidylinositols Chemical class 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 3
- 244000068988 Glycine max Species 0.000 description 3
- 235000010469 Glycine max Nutrition 0.000 description 3
- 241000598397 Schizochytrium sp. Species 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 235000021588 free fatty acids Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 description 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 2
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 2
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 241000239370 Euphausia superba Species 0.000 description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 235000021466 carotenoid Nutrition 0.000 description 2
- 150000001747 carotenoids Chemical class 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 description 2
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical class CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 2
- SSQPWTVBQMWLSZ-AAQCHOMXSA-N ethyl (5Z,8Z,11Z,14Z,17Z)-icosapentaenoate Chemical compound CCOC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC SSQPWTVBQMWLSZ-AAQCHOMXSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 229940013317 fish oils Drugs 0.000 description 2
- 235000004426 flaxseed Nutrition 0.000 description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 description 2
- 229960002600 icosapent ethyl Drugs 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 239000008601 oleoresin Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000008347 soybean phospholipid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- MJYQFWSXKFLTAY-OVEQLNGDSA-N (2r,3r)-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]butane-1,4-diol;(2r,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O.C1=C(O)C(OC)=CC(C[C@@H](CO)[C@H](CO)CC=2C=C(OC)C(O)=CC=2)=C1 MJYQFWSXKFLTAY-OVEQLNGDSA-N 0.000 description 1
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 241000238366 Cephalopoda Species 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 235000004347 Perilla Nutrition 0.000 description 1
- 244000124853 Perilla frutescens Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- JKQXZKUSFCKOGQ-LOFNIBRQSA-N all-trans-Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C JKQXZKUSFCKOGQ-LOFNIBRQSA-N 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 239000000828 canola oil Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000000944 linseed oil Substances 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 description 1
- 235000012680 lutein Nutrition 0.000 description 1
- 229960005375 lutein Drugs 0.000 description 1
- 239000001656 lutein Substances 0.000 description 1
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 description 1
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229940100691 oral capsule Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical class OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 229940005741 sunflower lecithin Drugs 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical group 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000012905 visible particle Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 description 1
- JKQXZKUSFCKOGQ-QAYBQHTQSA-N zeaxanthin Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-QAYBQHTQSA-N 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A23D9/007—Other edible oils or fats, e.g. shortenings, cooking oils characterised by ingredients other than fatty acid triglycerides
- A23D9/013—Other fatty acid esters, e.g. phosphatides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23J—PROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS
- A23J7/00—Phosphatide compositions for foodstuffs, e.g. lecithin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
-
- 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 invention relates to a pourable lipid composition
- a pourable lipid composition comprising: a) lecithin component selected from glycerophospholipids, glycolipids and combinations thereof; b) fatty acid ethyl esters comprising ethyl esters of omega-3 fatty acids selected from eicosapentaenoic acid, docosahexaenoic acid and combinations thereof; c) partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof; and d) optionally, triacylglycerides.
- the invention also provides an oral dosage unit comprising the aforementioned lipid composition and a process for the manufacture of said lipid composition.
- Omega-3 fatty acids also called w-3 fatty acids or n-3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their chemical structure.
- the three main naturally occurring omega- 3 fatty acids are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).
- ALA alpha-linolenic acid
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- ALA is found mainly in plant oils such as flaxseed, soybean, and canola oils.
- Sources of EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, krill oil, and certain algae.
- EPA acts as a precursor for prostaglandin-3 (which inhibits platelet aggregation), thromboxane-3, and leukotriene-5 eicosanoids.
- Vascepa ethyl eicosapentaenoic acid
- EPA a prescription drug containing only EPA
- DHA is a major fatty acid in brain phospholipids and the retina.
- the potential roles of DHA in the mechanisms of Alzheimer's disease are under active research.
- the European Food Safety Authority has approved health claims on omega-3 fatty acids. DHA/EPA for maintenance of normal cardiac function and normal (fasting) blood concentrations of triglycerides. DHA for maintenance of normal vision and normal brain function.
- omega-3 oils from these sources are deemed to be superior to omega-3 oils from plant sources, notably algae.
- Krill oil in particular is regarded as an excellent source of EPA and DHA. This is because krill oil, besides providing high levels of EPA and DHA, also provides the following favourable nutritional attributes:
- phospholipids - EPA and DHA in krill oil are more efficiently absorbed by the human body as they are largely contained in phospholipids, whereas in other sources, such as fish oil, these omega-3 fatty acids are contained in triglycerides, which are insoluble and require bile salts for their emulsification and absorption via the lymphatic system.
- Krill oil is an extract prepared from a species of Antarctic krill, Euphausia superba.
- Krill oil is characterized by a high glycerophospholipid content, phosphatidylcholine representing the bulk of the glycerophospholipids.
- krill oil contains triglycerides, diglycerides, monoglycerides and free fatty acids.
- Phospholipids typically represent 40-80 wt.% of the lipids contained in krill oil.
- Krill oils as well as fish oils have the drawback that there are concerns regarding sustainability. Furthermore, supplements based on these animal oil are not suited for vegetarians and vegans.
- US 2017/0182074 describes a liquid composition having a viscosity of less than 3000 mPa.s when measured at a temperature within the range 25-70°C, wherein the composition comprises (i) at least 80% by weight of a phospholipid-containing krill extract which has a viscosity of at least 3000 mPa.s when measured at a temperature where the liquid composition has a viscosity of less than 3000 mPa-s and (ii) no more than 20% by weight of a viscosity-reducing agent.
- Suitable viscosity-reducing agents include lower alcohols, benzyl alcohol, glycerol, and glycols (e.g.
- the US patent application also describes an oral capsule for human use including an encapsulated liquid composition, wherein (a) the capsule is made from a material which includes glycerol, and (b) the liquid composition comprises purified krill phospholipids and glycerol.
- CN 104306383 describes a soft capsule comprising phospholipid and unsaturated fatty acid ester.
- Example 1 describes the preparation of a capsule comprising a mixture of 65 parts by weight of phospholipid and 35 parts by weight of unsaturated fatty acid ester.
- CN 108265090 describes a method or preparing an fat or oil composition containing almost the same phospholipid-type DHA and phospholipid-type EPA as natural Antarctic krill oil.
- This fat or oil composition is prepared by transesterification of soybean lecithin with ethyl ester of EPA and ethyl ester of DHA.
- Lipoid GmbH (“Water soluble composition containing omega-3-fatty acids for use in dietetics and food', Research Disclosure, Kenneth Mason Publications, Hampshire, UK, vol. 527, no. 13) relates to water soluble compositions comprising omega-3 fatty acids.
- WO 2013/072767 relates to compositions comprising:
- a fatty acid oil mixture comprising EPA and DHA, wherein the EPA and DHA are in a form chosen from free fatty acid, ethyl ester, triglyceride and phospholipid, and
- WO 2008/068276 relates to soft gelatin capsules containing a liquid or pasty lipophilic phase and aspirin.
- WO 2015/142705 relates to dietary supplement compositions comprising an algae based oil having glycolipids and phospholipids and EPA fatty acids in combination with astaxanthin and hyaluronic acid or sodium hyaluronate.
- the present invention relates to a pourable lipid composition that provides very high levels of EPA and/or DHA in highly bioavailable form and that provides a suitable alternative for krill oil. More particularly, the invention relates to a pourable lipid composition comprising the following components:
- lecithin component selected from glycerophospholipids, glycolipids and combinations thereof, including at least 20 wt.%, calculated by weight of the lipid composition, of glycerophospholipids;
- (d) 0-30 wt.% triacylglycerides; wherein the lecithin component and the fatty acid ethyl esters are contained in the lipid composition in a weight ratio of less than 1.5:1; wherein the fatty acid ethyl esters comprise at least 35 wt.% of ethyl esters of omega-3 fatty acids selected from eicosapentaenoic acid, docosahexaenoic acid and combinations thereof; wherein the combination of components (a), (b), (c) and (d) comprises at least 90 wt.% of the composition; and wherein the combination of components (a) and (b) comprises at least 65 wt.% of the composition.
- the pourable lipid composition of the present invention can suitably be manufactured using only lipids from plant sources, e.g. using omega-3 oil from algae and lecithin from soybean or rapeseed.
- omega-3 oil can be converted into fatty acid ethyl esters by transesterification with ethanol.
- the lipid composition of the present invention can be provided in a shelf-stable liquid form. Furthermore, the emulsifying action of the glycerophospholipids aids the absorption of the apolar fatty acid ethyl esters and thereby increases bioavailability of the omega-3 fatty acids.
- the lipid composition of the present invention can contain high levels of EPA and/or DHA, allowing it to be used in supplements in the form of oral dosage units, such as capsules. Accordingly, the present invention also provides a dosage unit comprising 100-2000 mg of the aforementioned lipid composition.
- lipid composition of the present invention comprising the steps: a) partially transesterifying algal oil with ethanol to produce a transesterified composition containing fatty acid ethyl ester and partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof; b) combining the transesterified composition with lecithin.
- This process offers the advantage that EPA and DHA containing ethyl esters and EPA and DHA containing partial glycerides are produced in one step.
- the invention relates to the use of the present lipid composition in the treatment or prevention of cardiovascular-related disease, dry eye syndrome, Meibomian gland dysfunction, macular edema, Alzheimer’s disease and traumatic brain injury.
- a first aspect of the present invention relates to a pourable lipid composition
- a pourable lipid composition comprising the following components:
- lecithin component selected from glycerophospholipids, glycolipids and combinations thereof, including at least 20 wt.%, calculated by weight of the lipid composition, of glycerophospholipids;
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- liquid means that at 20 °C the lipid composition can be poured out a container.
- glycolides refers to fatty acid esters of glycerol (triacylglycerides, diacylglycerides and monoacylglycerides).
- fatty acid refers to a carboxylic acid with a long non-branched aliphatic chain of 6-24 carbon atoms.
- glycophospholipids refers to derivatives of glycerophosphoric acid that contains at least one fatty acid residue attached to the glycerol moiety.
- examples of glycerophospholipids include phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and phosphatidic acid (PA).
- glycolipid refers a monosaccharide or oligosaccharide bound to a lipid moiety by means of a glycosidic bond.
- Fatty acid concentrations as referred to herein, unless indicated otherwise, relate to the percentage by weight (% w/w) of the total combined amount of free fatty acids and fatty acid residues.
- the combination of components (a)) and (b) preferably comprises at least 75wt.%, more preferably at least 85 wt.% and most preferably at least 90 wt.% of the present lipid composition.
- the combination of components (a), (b), (c) and (d) preferably comprises at least 92 wt.%, more preferably at least 93 wt.% and most preferably at least 94 wt.% of the lipid composition.
- all the components a) to d) of the lipid composition are plant derived.
- the entire lipid composition is plant derived.
- the lipid composition of the present invention preferably provided at least 150 mg/g, more preferably 180-500 mg/g and most preferably 200-350 mg/g of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
- the lipid composition provides 12-80 mg/g, more preferably 18-70 mg/g and most preferably 24-65 mg/g alpha-linolenic acid (ALA).
- ALA alpha-linolenic acid
- the lipid composition of the present invention preferably comprises 33-58 wt.% lecithin component, more preferably 35-56 wt.% lecithin component, and most preferably 36-52 wt.% lecithin component.
- the lipid composition of the present invention preferably comprises 25-50 wt.% glycerophospholipids, more preferably 27-45 wt.% glycerophospholipids, and most preferably 28-40 wt.% glycerophospholipids.
- the lecithin component is obtained from soybean and/or rapeseed as the glycerophospholipids of these plant sources contain significant levels of omega-3 fatty acid residues in the form of alpha-linolenic acid.
- Preferably 2-15 wt.%, more preferably 3-12 wt.% and most preferably 4-9 wt.% of the fatty acid residues in the glycerophospholipids is alpha-linolenic acid residue (ALA).
- ALA alpha-linolenic acid residue
- the glycerophospholipids of the present invention typically do not contain more than a limited amount of EPA and/or DHA. Accordingly, in a preferred embodiment, 0-10 wt.%, more preferably 0-5 wt.% and most preferably 0-3 wt.% of the fatty acid residues in the glycerophospholipids are omega-3 fatty acids selected from EPA, DHA and combinations thereof. Unsaturated fatty acid residues preferably constitute at least 75 wt.%, more preferably at least 80 wt.% and most preferably at least 85 wt.% of the fatty acid residues in the glycerophospholipids.
- Polyunsaturated fatty acid residues preferably constitute at least 25 wt.%, more preferably at least 28 wt.% and most preferably at least 30 wt.% of the fatty acid residues in the glycerophospholipids.
- the glycerophospholipids in the lipid composition preferably comprise at least 10 wt.% phosphatidylcholine, more preferably 20-80 wt.% phosphatidylcholine, most preferably 30-60 wt.% phosphatidylcholine.
- the glycerophospholipids in the lipid composition preferably comprise at least 5 wt.% phosphatidylethanolamine, more preferably 10-50 wt.% phosphatidylethanolamine, most preferably 20-35 wt.% phosphatidylethanolamine.
- the lipid composition preferably comprises 35-66 wt.% fatty acid ethyl esters, more preferably 38-64 wt.% fatty acid ethyl esters and most preferably 40-63 wt.% fatty acid ethyl esters.
- the fatty acid ethyl esters comprise 0.5-30 wt.% eicosapentaenoic acid ethyl esters, more preferably 3-20 wt.% eicosapentaenoic acid ethyl esters, most preferably 5-15 wt.% eicosapentaenoic acid ethyl esters.
- the fatty acid ethyl esters comprise 30-60 wt.% docosahexaenoic acid ethyl esters, more preferably 32-50 wt.% docosahexaenoic acid ethyl esters, most preferably 35-40 wt.% docosahexaenoic acid ethyl esters.
- eicosapentaenoic acid ethyl esters and docosahexaenoic acid ethyl esters together constitute at least 30 wt.% , more preferably at least 40 wt.% and most preferably at least 50 wt.% of the fatty acid ethyl esters in the lipid composition.
- the lipid composition preferably comprises partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof. Partial glycerides containing omega-3 fatty acids may be produced in the preparation of the ethyl esters of fatty acids by transesterification of triglycerides with ethanol or they can be produced separately by transesterification of omega-3 oil with glycerol.
- the lipid composition preferably comprises 0.2-10 wt.%, more preferably 0.3-6 wt.% and most preferably 0.4-4 wt.% of the partial glycerides.
- At least 30 wt.%, more preferably at least 40 wt.% and most preferably at least 50 wt.% of the fatty acid residues in the partial glycerides are residues of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
- Triacylglycerides are preferably comprised in the lipid composition in a concentration of 0.1- 20 wt.%, more preferably a concentration of 0.2-10 wt.% and most preferably in a concentration of 0.3-5 wt.%.
- At least 35 wt.%, more preferably at least 40 wt.% and most preferably at least 50 wt.% of the fatty acid residues in the triacylglycerides are residues of omega-3 fatty acids selected from EPA, DHA and combinations thereof
- the ratio on a weight basis of the glycerophospholipids to the fatty acid ethyl esters in the lipid composition is preferably in the range of 1:3 to 1:1, more preferably in the range of 1:2.8 to 1:1.1, and most preferably in the range of 1:2.5 to 1:1.2.
- the ratio on a weight basis of the partial glycerides to the triacylglycerides in the lipid composition is preferably at least 1:30, more preferably at least 1:20, and most preferably in the range of 1:15 to 3:1.
- the lipid composition further comprises 0.001-1.5 wt.%, more preferably 0.1-1.2 wt.% and most preferably 0.3-0.9 wt.% carotenoids selected from beta carotene, lutein, astaxanthin, zeaxanthine.
- the lipid composition comprises 1-2,000 ppm (mg/kg), more preferably 100-1,500 ppm, most preferably 300-900 ppm astaxanthin.
- the lipid composition further comprises 0.01-2 wt.%, more preferably 0.1 -1.5 wt.% and most preferably 0.3-1 wt.% tocopherol.
- the pourable lipid composition of the present invention preferably has a viscosity of not more than 10,000 cP, more preferably of 200 to 9000 cP at 20 °C and a shear rate of 100 s 1 .
- the pourable lipid composition preferably shows less than 5 wt.%, more preferably less than 2 wt.% and most preferably less than 1 wt.% phase separation when the composition is kept in a sealed glass container at 20°C for 2 months.
- the wt.% phase separation is determined gravimetrically after decantation.
- Another aspect of the invention relates to an oral dosage unit comprising 100-2000 mg, more preferably comprising 300-1500 mg, most preferably comprising 400-1000 mg of the pourable lipid composition of the invention.
- the oral dosage unit provides 150-500 mg, more preferably 200-400 mg and most preferably 250-350 mg of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
- the oral dosage unit provides 10-100 mg, more preferably 15-80 mg and most preferably 20-50 mg ALA.
- the oral dosage unit of the present invention preferably is a capsule that is filled with the pourable lipid composition.
- the capsule comprises a gel film, more preferably a vegetarian gel film, i.e. a gel film that does not contain animal products such as gelatin.
- the capsule comprising the gel film preferably has a water content in the range of 5 to 30 wt.%, more preferably of 8 to 25 wt.%, most preferably in the range of 10 to 22 wt.%.
- the inventors have observed that water present in the capsule tends to migrate from the capsule towards the lipid composition, possibly due to the high phospholipid content of the lipid composition. This migration of water has an adverse effect on the capsule in that the corresponding lowering of the water content causes the gel film to become less elastic, brittle and fragile. At the same time, the increase in water content of the lipid composition can cause phase separation in the lipid composition, especially near the interface with the capsule.
- polar liquids examples include water, ethyl lactate, glycerol, ethylene glycol, propylene glycol, polyethylene glycol and combinations thereof. More preferably, the polar liquid is selected from water, ethyl lactate and combinations thereof. Most preferably, the polar liquid is ethyl lactate.
- the aforementioned polar liquid is preferably comprised in the pourable lipid composition in a concentration of 0.5-10 wt.%, more preferably in a concentration of 1-8 wt.% and most preferably in a concentration of 1.5-6 wt.%.
- Yet another aspect of the invention relates to a process for the manufacture of a lipid composition as described herein before, said process comprising the steps: a) partially transesterifying algal oil with ethanol to produce a transesterified composition containing fatty acid ethyl ester and partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof; b) combining the transesterified composition with lecithin.
- the present process yields a pourable lipid composition as defined herein before.
- the transesterified composition that is produced by the partial transesterification of algal oil preferably comprises 0.4-20 wt.%, more preferably 0.6-12 wt.% and most preferably 0.8-8 wt.% of the partial glycerides.
- At least 30 wt.%, more preferably at least 40 wt.% and most preferably at least 50 wt.% of the fatty acid residues in the algal are residues of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
- the algal oil used as a staring material in the present process preferably comprises at least 25 wt.%, more preferably at least 50 wt.% and most preferably at least 80 wt.% triacylglycerides.
- the algal oil employed in the present process preferably is an oil extracted from one or more of the genera Schizochytrium, Isochrysis, Nannochloris, Tetracelmis, Nannochloropsis, Chlorella. Most preferably, the algal oil is extracted from Schizochytrium.
- the transesterification is catalysed by an ethoxide salt selected from lithium ethoxide, sodium ethoxide, potassium ethoxide, preferably the ethoxide salt is sodium ethoxide.
- an ethoxide salt selected from lithium ethoxide, sodium ethoxide, potassium ethoxide, preferably the ethoxide salt is sodium ethoxide.
- the transesterification is catalysed by a lipase.
- the lecithin used in the present process is preferably selected from rapeseed lecithin, soy lecithin, sunflower lecithin, corn lecithin, cottonseed lecithin, sesame lecithin, perilla lecithin, linseed lecithin and combinations thereof. More preferably, the lecithin is selected from rapeseed lecithin, soy lecithin and combinations thereof.
- the lecithin employed in the present process preferably has a glycerophospholipid content of at least 40 wt.%, more preferably of at least 55 wt.% and most preferably of 60-95 wt.%.
- the ethanol and the algal oil are preferably combined in a weight ratio of 1:2 to 1:20, more preferably in a weight ratio of 1:2.5 to 1:16 and most preferably in a weight ratio of 1 :3 to 1 :6.
- Any ethanol remaining in the transesterified composition is preferably removed before the composition is combined with the lecithin.
- the transesterified composition and the lecithin are preferably combined in a weight ratio of 40:60 to 70:30, more preferably in a weight ratio of 42:58 to 68:32 and most preferably in a weight ratio of 45:55 to 65:35.
- Yet another aspect of the present invention relates to the use of the lipid composition of the present invention or of the oral dosage unit of the present invention for use in the treatment or prevention of cardiovascular-related disease, dry eye syndrome, Meibomian gland dysfunction, macular edema Alzheimer’s disease and traumatic brain injury.
- the lipid composition or oral dosage unit is used in the treatment or prevention of cardiovascular-related disease, more particularly a cardiovascular-related disease selected from high blood pressure, coronary heart disease, dyslipidemia, congestive heart failure and stroke.
- said use comprises orally administering of the lipid composition or the oral dosage unit. More preferably, the use comprises oral administration to provide a dose of at least 500 mg, more preferably a dose of 600-2,000 mg and most preferably a dose of 750- 950 mg of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
- Transesterified algae oil was prepared as follows. 100.3 g of omega-3 triglyceride oil from Schizochytrium sp. (DSM life’s Omega 60, 15% EPA 30% DHA) were warmed up to 50°C in a water bath under stirring and under nitrogen. 0.50 g of NaOH and 199.3 g of anhydrous ethanol were mixed at ambient temperature until complete dissolution. The ethanolic NaOH solution was added to the triglyceride oil. The mixture was initially cloudy but cleared after 1 min. The reaction was stopped after 5 min. The transesterified oil was mixed with 400 ml of hot tap water in a 1L-separating funnel which led to a stable, milky mixture. Sodium chloride was added to speed up phase separation. After two hours, both phases were still cloudy. The upper phase was washed a second time with 300 ml of demineralized water. The washed transesterified oil was filtered on a pleated filter to reduce its residual water amount.
- DSM life Omega 60,
- Powdered de-oiled rapeseed lecithin (98.5% acetone insolubles) was partially extracted with ethanol - water to obtain an extract rich in PC and PE and leaving a residue containing other complex and neutral lipids according to a method described by Patil et al. ( Extraction and purification of phosphatidylcholine from soyabean lecithin, Separation and Purification Technology 75 (2010) 138-144).
- transesterified oil 48.8 g of transesterified oil were mixed with 29.8 g of refined lecithin in a beaker at 50° under stirring during 15 min.
- the lipid composition so obtained had a very low, water-like viscosity and was stable under different storage conditions (room temperature, 4 °C in refrigerator) for days.
- the composition of the lipid composition is shown in Table 1.
- Transesterified algae oil was prepared as follows. 570.3 g of omega-3 triglyceride oil from Schizochytrium sp. (DSM life’s Omega 60, 15% EPA 30% DHA) were warmed up to 50°C in a 1 L stirred reactor on a water bath under nitrogen. 2.0 g of NaOH and 199.9 g of anhydrous ethanol were mixed at ambient temperature until complete dissolution. The NaOH ethanolic solution was added to the triglyceride oil. After 2 hours 300 g deionised water were added to stop the reaction and to wash out salts and other byproducts. The mixture was left to settle for 1 hour and 20 minutes and the water phase was withdrawn. The procedure was repeated with another 200 ml of deionised water and the water phase was again withdrawn after a settling time of 2 hours.
- transesterified oil phase so obtained was mixed with 5 g micro-crystalline cellulose to bind residual water. After letting the cellulose settle overnight the oil was filtered over paper filter to yield 511.15g of transesterified algae oil.
- the pourable lipid composition so obtained stayed homogeneous during several days at room temperature as well as at 4 °C in a refrigerator.
- composition of the lipid composition is shown in Table 2.
- Transesterified algae oil was prepared as follows. 10.04 kg of omega-3 triglyceride oil from Schizochytrium sp. (DSM life’s Omega 60, 15% EPA 30% DHA) were warmed up to 50°C in a 20 L stirred reactor with a heating jacket and recirculated water heater under nitrogen. 35.0 g of NaOH and 3.45 kg of anhydrous ethanol were mixed at ambient temperature until complete dissolution. After equilibrating the triglyceride oil at 50°C, the NaOH ethanolic solution was added to the oil by a dosage pump. After 2 hours of reaction 5 L deionised water were added to stop the reaction and to wash out salts and other byproducts.
- the pourable lipid composition so obtained was filled into bottles and used for test runs for encapsulation into softgel capsules.
- the composition of the lipid composition is shown in Table 3.
- Vegetarian Softgel capsules were prepared containing 850 mg of the pourable composition of Example 3, using Vegesoft® capsules, supplied by Eurocaps, Tredegar, South Wales, NP224EF, United Kingdom..
- Table 5 Pieces of Vegesoft® capsules (0.16 gram) were submerged in 15 grams of pourable lipid composition and left in there for three days. At the end of the storage time the pieces were removed from the lipid compositions, washed with hexane and allowed to dry. The weight of the pieces that had been stored in the different lipid compositions was compared with that of the original pieces. Also changes in the physical characteristics of the capsule materials and the lipid compositions were determined. The results are shown in Table 6.
- the observed weight loss is believed to have been caused by migration of water of from the capsule material into the lipid composition, possibly triggered by the high phospholipid content of the lipid composition. Removal of water from the capsule material reduces the elasticity and renders the material more fragile. Migration of water into the pourable liquid compositions can cause destabilisation resulting in the formation of a viscous layer on the surface of the capsule material.
- Transesterified algae oil was prepared using a two-fold excess of ethanol:
- the transesterified algae oil contained 4 wt.% partial glycerides in the form of monoglycerides.
- Lipid compositions were prepared by mixing the de-oiled rapeseed lecithin of Example 1 with the above mentioned transesterified algae oil and/or triglyceride oil.
- Composition 1 was a clear liquid that did not exhibit any phase separation.
- Composition A was unstable and separated into an clear, liquid upper phase and a brown jelly bottom phase.
- Composition B was unstable as it showed sedimentation of a viscous lecithin-rich phase.
- Composition C had to be stirred overnight in order to obtain a homogeneous viscous liquid.
- Viscosities of the stable lipid compositions were measured with a capillary viscometer at room temperature. The results are summarised in Table 8.
- Transesterified algae oil was prepared using an equimolar amount of ethanol:
- the transesterified algae oil contained 6 wt.% monoglycerides and 2 wt.% diglycerides.
- Lipid compositions were prepared by mixing 50 parts by weight of the de-oiled rapeseed lecithin of Example 1 with 50 parts by weight of the above mentioned transesterified algae oil.
- the lipid composition so obtained was stable and had a viscosity of 140 mPa.s.
- Transesterified algae oil was prepared using a sub-stochiometric amount of ethanol:
- the mixture was first washed with 60 ml water and then with 60 ml citric acid (5 g/100 mL). During each washing step air was bubbled through the emulsion. After each washing the emulsion was kept at 50°C to promote phase separation. In each step the oil phase was removed by means of decanting.
- the transesterified algae oil contained 19 wt.% monoglycerides and 2 wt.% diglycerides.
- Lipid compositions were prepared by mixing 62 parts by weight of the de-oiled rapeseed lecithin of Example 1 with 38 parts by weight of the above mentioned transesterified algae oil.
- the lipid composition so obtained was extremely stable and had a viscosity of 60 mPa.s.
Abstract
The invention relates to a pourable lipid composition comprising the following components: (a) 30-60 wt.% of lecithin component selected from glycerophospholipids, glycolipids and combinations thereof, including at least 20 wt.%, calculated by weight of the lipid composition, of glycerophospholipids; (b) 30-70 wt.% fatty acid ethyl esters; (c) 0.2-30 wt.% partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof; (d) 0-30 wt.% triacylglycerides; wherein the lecithin component and the fatty acid ethyl esters are contained in the lipid composition in a weight ratio of less than 1.5:1; wherein the fatty acid ethyl esters comprise at least 35 wt.% of ethyl esters of omega-3 fatty acids selected from eicosapentaenoic acid, docosahexaenoic acid and combinations thereof; wherein the combination of components (a), (b), (c) and (d) comprises at least 90 wt.% of the composition; and wherein the combination of components (a) and (b) comprises at least 65 wt.% of the composition. The pourable lipid composition of the present invention is shelf-stable and provides very high levels of EPA and/or DHA in highly bioavailable form. The pourable lipid composition can suitably be manufactured using only lipids from plant sources.
Description
LIPID COMPOSITION COMPRISING OMEGA-3 FATTY ACIDS
TECHNICAL FIELD OF THE INVENTION
The invention relates to a pourable lipid composition comprising: a) lecithin component selected from glycerophospholipids, glycolipids and combinations thereof; b) fatty acid ethyl esters comprising ethyl esters of omega-3 fatty acids selected from eicosapentaenoic acid, docosahexaenoic acid and combinations thereof; c) partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof; and d) optionally, triacylglycerides.
The invention also provides an oral dosage unit comprising the aforementioned lipid composition and a process for the manufacture of said lipid composition.
BACKGROUND OF THE INVENTION
Omega-3 fatty acids, also called w-3 fatty acids or n-3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their chemical structure. The three main naturally occurring omega- 3 fatty acids are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is found mainly in plant oils such as flaxseed, soybean, and canola oils. Sources of EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, krill oil, and certain algae.
Humans, like all other mammals, are unable to synthesize the essential omega-3 fatty acid ALA and can only obtain it through diet. However, they can use ALA, when available, to form EPA and DHA, be it in only very small amounts. Therefore, getting EPA and DHA from foods or dietary supplements is the only practical way to increase levels of these omega-3 fatty acids in the human body. Because EPA is also a precursor to DHA, ensuring a sufficient level of EPA on a diet containing neither EPA nor DHA is harder both because of the extra metabolic work required to synthesize EPA and because of the use of EPA to metabolize into
DHA. Medical conditions like diabetes or certain allergies may significantly limit the human body's capacity for metabolisation of EPA from ALA.
EPA acts as a precursor for prostaglandin-3 (which inhibits platelet aggregation), thromboxane-3, and leukotriene-5 eicosanoids. A recent multi-year study of Vascepa (ethyl eicosapentaenoic acid), a prescription drug containing only EPA, was shown to reduce heart attack, stroke, and cardiovascular death by 25% relative to a placebo in those with statin- resistant hypertriglyceridemia (Bhatt et al., Cardiovascular Risk Reduction with lcosapent Ethyl for Hypertriglyceridemia. New England Journal of Medicine (2019), 380: 11-22).
DHA is a major fatty acid in brain phospholipids and the retina. The potential roles of DHA in the mechanisms of Alzheimer's disease are under active research.
The European Food Safety Authority (EFSA) has approved health claims on omega-3 fatty acids. DHA/EPA for maintenance of normal cardiac function and normal (fasting) blood concentrations of triglycerides. DHA for maintenance of normal vision and normal brain function.
At the moment fish and krill are the major source of EPA and DHA used in supplements. The omega-3 oils from these sources, are deemed to be superior to omega-3 oils from plant sources, notably algae. Krill oil in particular is regarded as an excellent source of EPA and DHA. This is because krill oil, besides providing high levels of EPA and DHA, also provides the following favourable nutritional attributes:
• choline -an essential nutrient, and neurotransmitter precursor important to brain and muscle tissue;
• astaxanthin - a carotenoid with powerful antioxidant activity;
• phospholipids - EPA and DHA in krill oil are more efficiently absorbed by the human body as they are largely contained in phospholipids, whereas in other sources, such as fish oil, these omega-3 fatty acids are contained in triglycerides, which are insoluble and require bile salts for their emulsification and absorption via the lymphatic system.
Krill oil is an extract prepared from a species of Antarctic krill, Euphausia superba. Krill oil is characterized by a high glycerophospholipid content, phosphatidylcholine representing the bulk of the glycerophospholipids. Besides glycerophospholipids, krill oil contains triglycerides, diglycerides, monoglycerides and free fatty acids. Phospholipids typically represent 40-80 wt.% of the lipids contained in krill oil. Concentrations of the other lipids can vary considerably (see: Dan Xie et al., Antarctic Krill (Euphausia superba) Oil: A Comprehensive
Review of Chemical Composition, Extraction Technologies, Health Benefits, and Current Applications ; Comprehensive Reviews in Food Science and Food Safety Vol.18 (2019), 514- 534). EPA and DHA typically represent 14.3-28.0 wt.% and 7.1-15.7 wt.%, respectively of the fatty acids present in krill oil.
Krill oils as well as fish oils have the drawback that there are concerns regarding sustainability. Furthermore, supplements based on these animal oil are not suited for vegetarians and vegans.
US 2017/0182074 describes a liquid composition having a viscosity of less than 3000 mPa.s when measured at a temperature within the range 25-70°C, wherein the composition comprises (i) at least 80% by weight of a phospholipid-containing krill extract which has a viscosity of at least 3000 mPa.s when measured at a temperature where the liquid composition has a viscosity of less than 3000 mPa-s and (ii) no more than 20% by weight of a viscosity-reducing agent. Suitable viscosity-reducing agents include lower alcohols, benzyl alcohol, glycerol, and glycols (e.g. propylene glycol, or a polyethylene glycol, vegetable oils, medium-chain triglycerides and polysorbates. The US patent application also describes an oral capsule for human use including an encapsulated liquid composition, wherein (a) the capsule is made from a material which includes glycerol, and (b) the liquid composition comprises purified krill phospholipids and glycerol.
CN 104306383 describes a soft capsule comprising phospholipid and unsaturated fatty acid ester. Example 1 describes the preparation of a capsule comprising a mixture of 65 parts by weight of phospholipid and 35 parts by weight of unsaturated fatty acid ester.
CN 108265090 describes a method or preparing an fat or oil composition containing almost the same phospholipid-type DHA and phospholipid-type EPA as natural Antarctic krill oil.
This fat or oil composition is prepared by transesterification of soybean lecithin with ethyl ester of EPA and ethyl ester of DHA.
US 2009/074857 describes lipid compositions comprising a mixture of serine glycerophospholipid conjugates with EPA and DHA.
Lipoid GmbH (“Water soluble composition containing omega-3-fatty acids for use in dietetics and food', Research Disclosure, Kenneth Mason Publications, Hampshire, UK, vol. 527, no. 13) relates to water soluble compositions comprising omega-3 fatty acids.
WO 2013/072767 relates to compositions comprising:
• a fatty acid oil mixture comprising EPA and DHA, wherein the EPA and DHA are in a form chosen from free fatty acid, ethyl ester, triglyceride and phospholipid, and
• salicylate.
WO 2008/068276 relates to soft gelatin capsules containing a liquid or pasty lipophilic phase and aspirin.
WO 2015/142705 relates to dietary supplement compositions comprising an algae based oil having glycolipids and phospholipids and EPA fatty acids in combination with astaxanthin and hyaluronic acid or sodium hyaluronate.
SUMMARY OF THE INVENTION
The present invention relates to a pourable lipid composition that provides very high levels of EPA and/or DHA in highly bioavailable form and that provides a suitable alternative for krill oil. More particularly, the invention relates to a pourable lipid composition comprising the following components:
(a) 30-60 wt.% of lecithin component selected from glycerophospholipids, glycolipids and combinations thereof, including at least 20 wt.%, calculated by weight of the lipid composition, of glycerophospholipids;
(b) 30-70 wt.% fatty acid ethyl esters;
(c) 0.2-30 wt.% partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof;
(d) 0-30 wt.% triacylglycerides; wherein the lecithin component and the fatty acid ethyl esters are contained in the lipid composition in a weight ratio of less than 1.5:1; wherein the fatty acid ethyl esters comprise at least 35 wt.% of ethyl esters of omega-3 fatty acids selected from eicosapentaenoic acid, docosahexaenoic acid and combinations thereof; wherein the combination of components (a), (b), (c) and (d) comprises at least 90 wt.% of the composition; and wherein the combination of components (a) and (b) comprises at least 65 wt.% of the composition.
The pourable lipid composition of the present invention can suitably be manufactured using only lipids from plant sources, e.g. using omega-3 oil from algae and lecithin from soybean or
rapeseed. The omega-3 oil can be converted into fatty acid ethyl esters by transesterification with ethanol.
Despite the high content of glycerophospholipids, the lipid composition of the present invention can be provided in a shelf-stable liquid form. Furthermore, the emulsifying action of the glycerophospholipids aids the absorption of the apolar fatty acid ethyl esters and thereby increases bioavailability of the omega-3 fatty acids.
The lipid composition of the present invention can contain high levels of EPA and/or DHA, allowing it to be used in supplements in the form of oral dosage units, such as capsules. Accordingly, the present invention also provides a dosage unit comprising 100-2000 mg of the aforementioned lipid composition.
Further provided is a process for the manufacture of the lipid composition of the present invention, said process comprising the steps: a) partially transesterifying algal oil with ethanol to produce a transesterified composition containing fatty acid ethyl ester and partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof; b) combining the transesterified composition with lecithin.
This process offers the advantage that EPA and DHA containing ethyl esters and EPA and DHA containing partial glycerides are produced in one step.
Finally, the invention relates to the use of the present lipid composition in the treatment or prevention of cardiovascular-related disease, dry eye syndrome, Meibomian gland dysfunction, macular edema, Alzheimer’s disease and traumatic brain injury.
DETAILED DESCRIPTION OF THE INVENTION
A first aspect of the present invention relates to a pourable lipid composition comprising the following components:
(a) 30-60 wt.% of lecithin component selected from glycerophospholipids, glycolipids and combinations thereof, including at least 20 wt.%, calculated by weight of the lipid composition, of glycerophospholipids;
(b) 30-70 wt.% fatty acid ethyl esters;
(c) 0.2-30 wt.% partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof;
(d) 0-30 wt.% triacylglycerides; wherein the lecithin component and the fatty acid ethyl esters are contained in the lipid composition in a weight ratio of less than 1.5:1, preferably in a weight ratio of less than 1.2:1, most preferably in a weight ratio of less than 1:1; wherein the fatty acid ethyl esters comprise at least 35 wt.% of ethyl esters of omega-3 fatty acids selected from eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and combinations thereof; wherein the combination of components (a), (b), (c) and (d) comprises at least 90 wt.% of the composition; and wherein the combination of components (a) and (b) comprises at least 65 wt.%.
The term “pourable” as used herein means that at 20 °C the lipid composition can be poured out a container.
The “glycerides” as used herein refers to fatty acid esters of glycerol (triacylglycerides, diacylglycerides and monoacylglycerides).
The term “fatty acid” as used herein refers to a carboxylic acid with a long non-branched aliphatic chain of 6-24 carbon atoms.
The term “glycerophospholipids” as used herein refers to derivatives of glycerophosphoric acid that contains at least one fatty acid residue attached to the glycerol moiety. Examples of glycerophospholipids include phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and phosphatidic acid (PA).
The term “glycolipid” as used herein refers a monosaccharide or oligosaccharide bound to a lipid moiety by means of a glycosidic bond.
Fatty acid concentrations as referred to herein, unless indicated otherwise, relate to the percentage by weight (% w/w) of the total combined amount of free fatty acids and fatty acid residues.
The combination of components (a)) and (b) preferably comprises at least 75wt.%, more preferably at least 85 wt.% and most preferably at least 90 wt.% of the present lipid composition.
The combination of components (a), (b), (c) and (d) preferably comprises at least 92 wt.%, more preferably at least 93 wt.% and most preferably at least 94 wt.% of the lipid composition.
According to a particularly preferred embodiment of the present invention, all the components a) to d) of the lipid composition are plant derived. Most preferably, the entire lipid composition is plant derived.
The lipid composition of the present invention preferably provided at least 150 mg/g, more preferably 180-500 mg/g and most preferably 200-350 mg/g of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
In a further preferred embodiment, the lipid composition provides 12-80 mg/g, more preferably 18-70 mg/g and most preferably 24-65 mg/g alpha-linolenic acid (ALA).
The lipid composition of the present invention preferably comprises 33-58 wt.% lecithin component, more preferably 35-56 wt.% lecithin component, and most preferably 36-52 wt.% lecithin component.
The lipid composition of the present invention preferably comprises 25-50 wt.% glycerophospholipids, more preferably 27-45 wt.% glycerophospholipids, and most preferably 28-40 wt.% glycerophospholipids.
According to a particularly preferred embodiment, the lecithin component is obtained from soybean and/or rapeseed as the glycerophospholipids of these plant sources contain significant levels of omega-3 fatty acid residues in the form of alpha-linolenic acid.
Preferably 2-15 wt.%, more preferably 3-12 wt.% and most preferably 4-9 wt.% of the fatty acid residues in the glycerophospholipids is alpha-linolenic acid residue (ALA).
Unlike the fatty acid ethyl esters, the glycerophospholipids of the present invention typically do not contain more than a limited amount of EPA and/or DHA. Accordingly, in a preferred embodiment, 0-10 wt.%, more preferably 0-5 wt.% and most preferably 0-3 wt.% of the fatty acid residues in the glycerophospholipids are omega-3 fatty acids selected from EPA, DHA and combinations thereof.
Unsaturated fatty acid residues preferably constitute at least 75 wt.%, more preferably at least 80 wt.% and most preferably at least 85 wt.% of the fatty acid residues in the glycerophospholipids.
Polyunsaturated fatty acid residues preferably constitute at least 25 wt.%, more preferably at least 28 wt.% and most preferably at least 30 wt.% of the fatty acid residues in the glycerophospholipids.
The glycerophospholipids in the lipid composition preferably comprise at least 10 wt.% phosphatidylcholine, more preferably 20-80 wt.% phosphatidylcholine, most preferably 30-60 wt.% phosphatidylcholine.
The glycerophospholipids in the lipid composition preferably comprise at least 5 wt.% phosphatidylethanolamine, more preferably 10-50 wt.% phosphatidylethanolamine, most preferably 20-35 wt.% phosphatidylethanolamine.
The lipid composition preferably comprises 35-66 wt.% fatty acid ethyl esters, more preferably 38-64 wt.% fatty acid ethyl esters and most preferably 40-63 wt.% fatty acid ethyl esters.
According to another preferred embodiment, the fatty acid ethyl esters comprise 0.5-30 wt.% eicosapentaenoic acid ethyl esters, more preferably 3-20 wt.% eicosapentaenoic acid ethyl esters, most preferably 5-15 wt.% eicosapentaenoic acid ethyl esters.
According to a preferred embodiment, the fatty acid ethyl esters comprise 30-60 wt.% docosahexaenoic acid ethyl esters, more preferably 32-50 wt.% docosahexaenoic acid ethyl esters, most preferably 35-40 wt.% docosahexaenoic acid ethyl esters.
Preferably, eicosapentaenoic acid ethyl esters and docosahexaenoic acid ethyl esters together constitute at least 30 wt.% , more preferably at least 40 wt.% and most preferably at least 50 wt.% of the fatty acid ethyl esters in the lipid composition.
The lipid composition preferably comprises partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof. Partial glycerides containing omega-3 fatty acids may be produced in the preparation of the ethyl esters of fatty acids by transesterification of triglycerides with ethanol or they can be produced separately by transesterification of omega-3 oil with glycerol. The lipid composition preferably comprises
0.2-10 wt.%, more preferably 0.3-6 wt.% and most preferably 0.4-4 wt.% of the partial glycerides.
According to a particularly preferred embodiment at least 30 wt.%, more preferably at least 40 wt.% and most preferably at least 50 wt.% of the fatty acid residues in the partial glycerides are residues of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
Triacylglycerides are preferably comprised in the lipid composition in a concentration of 0.1- 20 wt.%, more preferably a concentration of 0.2-10 wt.% and most preferably in a concentration of 0.3-5 wt.%.
Preferably, at least 35 wt.%, more preferably at least 40 wt.% and most preferably at least 50 wt.% of the fatty acid residues in the triacylglycerides are residues of omega-3 fatty acids selected from EPA, DHA and combinations thereof
The ratio on a weight basis of the glycerophospholipids to the fatty acid ethyl esters in the lipid composition is preferably in the range of 1:3 to 1:1, more preferably in the range of 1:2.8 to 1:1.1, and most preferably in the range of 1:2.5 to 1:1.2.
The ratio on a weight basis of the partial glycerides to the triacylglycerides in the lipid composition is preferably at least 1:30, more preferably at least 1:20, and most preferably in the range of 1:15 to 3:1.
In an advantageous embodiment, the lipid composition further comprises 0.001-1.5 wt.%, more preferably 0.1-1.2 wt.% and most preferably 0.3-0.9 wt.% carotenoids selected from beta carotene, lutein, astaxanthin, zeaxanthine.
According to a particularly preferred embodiment, the lipid composition comprises 1-2,000 ppm (mg/kg), more preferably 100-1,500 ppm, most preferably 300-900 ppm astaxanthin.
In another preferred embodiment, the lipid composition further comprises 0.01-2 wt.%, more preferably 0.1 -1.5 wt.% and most preferably 0.3-1 wt.% tocopherol.
The pourable lipid composition of the present invention preferably has a viscosity of not more than 10,000 cP, more preferably of 200 to 9000 cP at 20 °C and a shear rate of 100 s 1.
The pourable lipid composition preferably shows less than 5 wt.%, more preferably less than 2 wt.% and most preferably less than 1 wt.% phase separation when the composition is kept in a sealed glass container at 20°C for 2 months. The wt.% phase separation is determined gravimetrically after decantation.
Another aspect of the invention relates to an oral dosage unit comprising 100-2000 mg, more preferably comprising 300-1500 mg, most preferably comprising 400-1000 mg of the pourable lipid composition of the invention.
Preferably, the oral dosage unit provides 150-500 mg, more preferably 200-400 mg and most preferably 250-350 mg of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
In a further preferred embodiment, the oral dosage unit provides 10-100 mg, more preferably 15-80 mg and most preferably 20-50 mg ALA.
The oral dosage unit of the present invention preferably is a capsule that is filled with the pourable lipid composition. Preferably, the capsule comprises a gel film, more preferably a vegetarian gel film, i.e. a gel film that does not contain animal products such as gelatin.
The capsule comprising the gel film preferably has a water content in the range of 5 to 30 wt.%, more preferably of 8 to 25 wt.%, most preferably in the range of 10 to 22 wt.%.
The inventors have observed that water present in the capsule tends to migrate from the capsule towards the lipid composition, possibly due to the high phospholipid content of the lipid composition. This migration of water has an adverse effect on the capsule in that the corresponding lowering of the water content causes the gel film to become less elastic, brittle and fragile. At the same time, the increase in water content of the lipid composition can cause phase separation in the lipid composition, especially near the interface with the capsule.
The inventors have found that this unwanted water migration can be prevented or at least minimised by including a polar liquid in the lipid composition. Examples of polar liquids that may be employed include water, ethyl lactate, glycerol, ethylene glycol, propylene glycol, polyethylene glycol and combinations thereof. More preferably, the polar liquid is selected from water, ethyl lactate and combinations thereof. Most preferably, the polar liquid is ethyl lactate.
The aforementioned polar liquid is preferably comprised in the pourable lipid composition in a concentration of 0.5-10 wt.%, more preferably in a concentration of 1-8 wt.% and most preferably in a concentration of 1.5-6 wt.%.
Yet another aspect of the invention relates to a process for the manufacture of a lipid composition as described herein before, said process comprising the steps: a) partially transesterifying algal oil with ethanol to produce a transesterified composition containing fatty acid ethyl ester and partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof; b) combining the transesterified composition with lecithin.
In a preferred embodiment, the present process yields a pourable lipid composition as defined herein before.
The transesterified composition that is produced by the partial transesterification of algal oil preferably comprises 0.4-20 wt.%, more preferably 0.6-12 wt.% and most preferably 0.8-8 wt.% of the partial glycerides.
Preferably, at least 30 wt.%, more preferably at least 40 wt.% and most preferably at least 50 wt.% of the fatty acid residues in the algal are residues of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
The algal oil used as a staring material in the present process preferably comprises at least 25 wt.%, more preferably at least 50 wt.% and most preferably at least 80 wt.% triacylglycerides.
The algal oil employed in the present process preferably is an oil extracted from one or more of the genera Schizochytrium, Isochrysis, Nannochloris, Tetracelmis, Nannochloropsis, Chlorella. Most preferably, the algal oil is extracted from Schizochytrium.
In one embodiment of the present process, the transesterification is catalysed by an ethoxide salt selected from lithium ethoxide, sodium ethoxide, potassium ethoxide, preferably the ethoxide salt is sodium ethoxide.
In another embodiment of the present process, the transesterification is catalysed by a lipase.
The lecithin used in the present process is preferably selected from rapeseed lecithin, soy lecithin, sunflower lecithin, corn lecithin, cottonseed lecithin, sesame lecithin, perilla lecithin, linseed lecithin and combinations thereof. More preferably, the lecithin is selected from rapeseed lecithin, soy lecithin and combinations thereof.
The lecithin employed in the present process preferably has a glycerophospholipid content of at least 40 wt.%, more preferably of at least 55 wt.% and most preferably of 60-95 wt.%.
In the present process, prior to transesterification the ethanol and the algal oil are preferably combined in a weight ratio of 1:2 to 1:20, more preferably in a weight ratio of 1:2.5 to 1:16 and most preferably in a weight ratio of 1 :3 to 1 :6.
Any ethanol remaining in the transesterified composition is preferably removed before the composition is combined with the lecithin.
The transesterified composition and the lecithin are preferably combined in a weight ratio of 40:60 to 70:30, more preferably in a weight ratio of 42:58 to 68:32 and most preferably in a weight ratio of 45:55 to 65:35.
Yet another aspect of the present invention relates to the use of the lipid composition of the present invention or of the oral dosage unit of the present invention for use in the treatment or prevention of cardiovascular-related disease, dry eye syndrome, Meibomian gland dysfunction, macular edema Alzheimer’s disease and traumatic brain injury. Most preferably, the lipid composition or oral dosage unit is used in the treatment or prevention of cardiovascular-related disease, more particularly a cardiovascular-related disease selected from high blood pressure, coronary heart disease, dyslipidemia, congestive heart failure and stroke.
Preferably, said use comprises orally administering of the lipid composition or the oral dosage unit. More preferably, the use comprises oral administration to provide a dose of at least 500 mg, more preferably a dose of 600-2,000 mg and most preferably a dose of 750- 950 mg of omega-3 fatty acids selected from EPA, DHA and combinations thereof.
The invention is further illustrated by the following non-limiting examples.
EXAMPLES
Example 1
Transesterified algae oil was prepared as follows. 100.3 g of omega-3 triglyceride oil from Schizochytrium sp. (DSM life’s Omega 60, 15% EPA 30% DHA) were warmed up to 50°C in a water bath under stirring and under nitrogen. 0.50 g of NaOH and 199.3 g of anhydrous ethanol were mixed at ambient temperature until complete dissolution. The ethanolic NaOH solution was added to the triglyceride oil. The mixture was initially cloudy but cleared after 1 min. The reaction was stopped after 5 min. The transesterified oil was mixed with 400 ml of hot tap water in a 1L-separating funnel which led to a stable, milky mixture. Sodium chloride was added to speed up phase separation. After two hours, both phases were still cloudy. The upper phase was washed a second time with 300 ml of demineralized water. The washed transesterified oil was filtered on a pleated filter to reduce its residual water amount.
Powdered de-oiled rapeseed lecithin (98.5% acetone insolubles) was partially extracted with ethanol - water to obtain an extract rich in PC and PE and leaving a residue containing other complex and neutral lipids according to a method described by Patil et al. ( Extraction and purification of phosphatidylcholine from soyabean lecithin, Separation and Purification Technology 75 (2010) 138-144).
48.8 g of transesterified oil were mixed with 29.8 g of refined lecithin in a beaker at 50° under stirring during 15 min.
The lipid composition so obtained had a very low, water-like viscosity and was stable under different storage conditions (room temperature, 4 °C in refrigerator) for days. The composition of the lipid composition is shown in Table 1.
1 16% phosphatidylcholine, 4% phosphatidyl ethanolamine, 10% phosphatidylinositol (De oiled rapeseed lecithin powder, Lecico RAP P 200 IP)
Example 2
Transesterified algae oil was prepared as follows. 570.3 g of omega-3 triglyceride oil from Schizochytrium sp. (DSM life’s Omega 60, 15% EPA 30% DHA) were warmed up to 50°C in a 1 L stirred reactor on a water bath under nitrogen. 2.0 g of NaOH and 199.9 g of anhydrous ethanol were mixed at ambient temperature until complete dissolution. The NaOH ethanolic solution was added to the triglyceride oil. After 2 hours 300 g deionised water were added to stop the reaction and to wash out salts and other byproducts. The mixture was left to settle for 1 hour and 20 minutes and the water phase was withdrawn. The procedure was repeated with another 200 ml of deionised water and the water phase was again withdrawn after a settling time of 2 hours.
The transesterified oil phase so obtained was mixed with 5 g micro-crystalline cellulose to bind residual water. After letting the cellulose settle overnight the oil was filtered over paper filter to yield 511.15g of transesterified algae oil.
510.0 g of the transesterified oil were mixed with 510.1 g de-oiled rapeseed lecithin (98.5% acetone insolubles) by repeatedly blending with a kitchen blender until no particles of lecithin were visible any more. Finally 10 g of astaxanthin oleoresin (10% astaxanthin) were admixed by the same mixing device.
The pourable lipid composition so obtained stayed homogeneous during several days at room temperature as well as at 4 °C in a refrigerator.
The composition of the lipid composition is shown in Table 2.
1 14% phosphatidylcholine, 8.4% phosphatidyl ethanolamine, 8.9% phosphatidylinositol, 2.0% phosphatidic acid, and 2.0% of lyso-phosphatidylcholine
Example 3
Transesterified algae oil was prepared as follows. 10.04 kg of omega-3 triglyceride oil from Schizochytrium sp. (DSM life’s Omega 60, 15% EPA 30% DHA) were warmed up to 50°C in a 20 L stirred reactor with a heating jacket and recirculated water heater under nitrogen. 35.0
g of NaOH and 3.45 kg of anhydrous ethanol were mixed at ambient temperature until complete dissolution. After equilibrating the triglyceride oil at 50°C, the NaOH ethanolic solution was added to the oil by a dosage pump. After 2 hours of reaction 5 L deionised water were added to stop the reaction and to wash out salts and other byproducts. The mixture was left to settle for 2 hours before the water phase was withdrawn. The procedure was repeated with another 3.5 L of deionised water and the water phase was again withdrawn after a settling time of 10 minutes. 400 g microcrystalline cellulose were added to the transesterified oil to bind residual water. After letting the cellulose settle over night the oil was transferred from the reactor to a storage tank via a 1 micrometer in-line filter.
18.99 kg of the transesterified algae oil were mixed with 18.95 kg de-oiled rapeseed lecithin (98.5% acetone insolubles) in a 80 L mixing vessel equipped with a high-shear mixer. While lecithine was added the mixer was operated at maximum speed. Afterwards it was left on for 2 hours at medium speed until there were no visible particles of lecithin any more. Then 340 g of astaxanthin oleoresin (10% astaxanthin) and 425 g of a tocopherol mixture were added while blending at high speed for 15 minutes.
The pourable lipid composition so obtained was filled into bottles and used for test runs for encapsulation into softgel capsules. The composition of the lipid composition is shown in Table 3.
Example 4
Vegetarian Softgel capsules were prepared containing 850 mg of the pourable composition of Example 3, using Vegesoft® capsules, supplied by Eurocaps, Tredegar, South Wales, NP224EF, United Kingdom..
After one month storage under ambient conditions, the filled capsules still exhibited adequate mechanical integrity.
Example 5
Experiments were carried out to establish the impact of different pourable lipid compositions on the capsule material of the capsules described in Example 4. The compositions of the different pourable lipid compositions are shown in Table 5 (lipid composition 1 is identical to the lipid composition of Example 2).
Table 5
Pieces of Vegesoft® capsules (0.16 gram) were submerged in 15 grams of pourable lipid composition and left in there for three days. At the end of the storage time the pieces were removed from the lipid compositions, washed with hexane and allowed to dry. The weight of
the pieces that had been stored in the different lipid compositions was compared with that of the original pieces. Also changes in the physical characteristics of the capsule materials and the lipid compositions were determined. The results are shown in Table 6.
The observed weight loss is believed to have been caused by migration of water of from the capsule material into the lipid composition, possibly triggered by the high phospholipid content of the lipid composition. Removal of water from the capsule material reduces the elasticity and renders the material more fragile. Migration of water into the pourable liquid compositions can cause destabilisation resulting in the formation of a viscous layer on the surface of the capsule material.
Example 6
Transesterified algae oil was prepared using a two-fold excess of ethanol:
• 175 g of non winterized algae oil having a DHA content of 45.8% and an EPA content of 1.5% (AlgalPure DHA®, ex Bioriginal) were esterified with 54.6 g ethanol (PhEUR >99,5%), using 4.8 g sodium ethanolate as catalyst. The reaction mixture was stirred on a water bath at 50 °C for 1 h.
• Next, the mixture was washed twice with 80 ml water and once with 80 ml citric acid (5 g/100 ml_). During each washing step air was bubbled through the emulsion. After each washing the emulsion was kept at 50°C to promote phase separation. In each step the oil phase was removed by means of decanting.
• Finally, the decanted oil was filtered over cellulose to remove moisture.
The transesterified algae oil contained 4 wt.% partial glycerides in the form of monoglycerides.
Lipid compositions were prepared by mixing the de-oiled rapeseed lecithin of Example 1 with the above mentioned transesterified algae oil and/or triglyceride oil.
1 Added in the form of mono/diglycerides (SaporePuro, Gioia Group S.R.L., Italy)
2 DSM life’s Omega 60, 15% EPA 30% DHA
Composition 1 was a clear liquid that did not exhibit any phase separation.
Composition A was unstable and separated into an clear, liquid upper phase and a brown jelly bottom phase.
Composition B was unstable as it showed sedimentation of a viscous lecithin-rich phase.
Composition C had to be stirred overnight in order to obtain a homogeneous viscous liquid.
Viscosities of the stable lipid compositions were measured with a capillary viscometer at room temperature. The results are summarised in Table 8.
Example 7
Transesterified algae oil was prepared using an equimolar amount of ethanol:
• 192 g of algae oil containing 15% EPA and 30% DHA (DSM life’s Omega 60) were esterified with 26 g ethanol (PhEUR >99,5%), using 5.7 g sodium ethanolate as catalyst. The reaction mixture was stirred on a water bath at 50 °C for 1 h.
• Next, the mixture was successively washed with 60 ml water and with 60 ml citric acid (5 g/100 ml_). During each washing step air was bubbled through the emulsion. After each washing the emulsion was kept at 50°C to promote phase separation. In each step the oil phase was removed by means of decanting.
• Finally, the decanted oil was filtered over cellulose to remove moisture.
The transesterified algae oil contained 6 wt.% monoglycerides and 2 wt.% diglycerides.
Lipid compositions were prepared by mixing 50 parts by weight of the de-oiled rapeseed lecithin of Example 1 with 50 parts by weight of the above mentioned transesterified algae oil.
The lipid composition so obtained was stable and had a viscosity of 140 mPa.s.
Example 8
Transesterified algae oil was prepared using a sub-stochiometric amount of ethanol:
• 191 g of algae oil containing 15% EPA and 30% DHA (DSM life’s Omega 60) were esterified with 15 g ethanol (PhEUR >99,5%), using 5.1 g sodium ethanolate as catalyst. The reaction mixture was stirred on a water bath at 50 °C for 1 h.
• The mixture was first washed with 60 ml water and then with 60 ml citric acid (5 g/100 mL). During each washing step air was bubbled through the emulsion. After each washing the emulsion was kept at 50°C to promote phase separation. In each step the oil phase was removed by means of decanting.
• Finally, the decanted oil was filtered over cellulose to remove moisture.
The transesterified algae oil contained 19 wt.% monoglycerides and 2 wt.% diglycerides.
Lipid compositions were prepared by mixing 62 parts by weight of the de-oiled rapeseed lecithin of Example 1 with 38 parts by weight of the above mentioned transesterified algae oil.
The lipid composition so obtained was extremely stable and had a viscosity of 60 mPa.s.
Claims
1. A pourable lipid composition comprising the following components:
(a) 30-60 wt.% of lecithin component selected from glycerophospholipids, glycolipids and combinations thereof, including at least 20 wt.%, calculated by weight of the lipid composition, of glycerophospholipids;
(b) 30-70 wt.% fatty acid ethyl esters;
(c) 0.2-30 wt.% partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof;
(d) 0-30 wt.% triacylglycerides; wherein the lecithin component and the fatty acid ethyl esters are contained in the lipid composition in a weight ratio of less than 1.5:1; wherein the fatty acid ethyl esters comprise at least 35 wt.% of ethyl esters of omega-3 fatty acids selected from eicosapentaenoic acid, docosahexaenoic acid and combinations thereof; wherein the combination of components (a), (b), (c) and (d) comprises at least 90 wt.% of the composition; and wherein the combination of components (a) and (b) comprises at least 65 wt.% of the composition.
2. The lipid composition according to claim 1, wherein the combination of components (a) and (b) comprises at least 75 wt.% of the composition.
3. The lipid composition according to claim 1 or 2, wherein the composition comprises 25- 50 wt.% glycerophospholipids,.
4. The lipid composition according to any one of the preceding claims, wherein 2-10 wt.% of the fatty acid residues in the glycerophospholipids is alpha-linolenic acid residue.
5. The lipid composition according to any one of the preceding claims, wherein the fatty acid ethyl esters comprise 0.5-30 wt.% eicosapentaenoic acid ethyl esters.
6. The lipid composition according to any one of the preceding claims, wherein the fatty acid ethyl esters comprise 30-60 wt.% docosahexaenoic acid ethyl esters.
7. The lipid composition according to any one of the preceding claims, wherein the composition comprises 35-66 wt.% fatty acid ethyl esters.
8. The lipid composition according to any one of the preceding claims, wherein the composition comprises 0.2-10 wt.% of the partial glycerides.
9. The lipid composition according to any of the preceding claims, wherein the ratio on a weight basis of the glycerophospholipids to the fatty acid ethyl esters is 1:3 to 1:1.
10. The lipid composition according to any of the preceding claims, wherein the glycerophospholipids comprise at least 10 wt.% phosphatidylcholine, preferably 20- 80wt.% phosphatidylcholine, most preferably 30-60 wt.% phosphatidylcholine.
11. An oral dosage unit comprising 100-2,000 mg of the lipid composition according to any of the preceding claims, preferably comprising 300-1 ,500 mg of the lipid composition, most preferably 400-1 ,000 mg of the lipid composition.
12. Oral dosage unit according to claim 11 , wherein the oral dosage unit comprises a capsule that comprises a gel film having a water content in the range of 5 to 30 wt.%, and wherein the capsule holds the lipid composition, said lipid composition containing 0.5-10 wt.% of polar liquid selected from water, ethyl lactate, glycerol, ethylene glycol, propylene glycol, polyethylene glycol and combinations thereof.
13. A process for the manufacture of a lipid composition according to any of the preceding claims, comprising the steps: a) partially transesterifying algal oil with ethanol to produce a transesterified composition containing fatty acid ethyl ester and partial glycerides selected from monoacylglycerides, diacylglycerides and combinations thereof; b) combining the transesterified composition with lecithin.
14. The process according to claim 13, wherein the algal oil is an oil extracted from one or more of the genera Schizochytrium, Isochrysis, Nannochloris, Tetracelmis, Nannochloropsis, Chlorella.
15. Lipid composition according to any one of claims 1-11 or oral dosage unit according to claim 12 for use in the treatment or prevention of cardiovascular-related disease, dry eye syndrome, Meibomian gland dysfunction, macular edema Alzheimer’s disease and traumatic brain injury.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP20155364.1 | 2020-02-04 | ||
EP20155364 | 2020-02-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021156385A1 true WO2021156385A1 (en) | 2021-08-12 |
Family
ID=69468422
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2021/052702 WO2021156385A1 (en) | 2020-02-04 | 2021-02-04 | Lipid composition comprising omega-3 fatty acids |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2021156385A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023126026A3 (en) * | 2021-12-29 | 2023-08-24 | 中国科学院上海药物研究所 | Epa-ee lipid nanocomposite, formulation thereof, preparation method therefor, and application thereof |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008068276A1 (en) | 2006-12-06 | 2008-06-12 | Ibsa Institut Biochimique S.A. | Soft gelatin capsules comprising acetylsalicylic acid |
US20090074857A1 (en) | 2003-10-22 | 2009-03-19 | Enzymotec Ltd. | Glycerophospholipids for the improvement of cognitive functions |
WO2013072767A1 (en) | 2011-11-18 | 2013-05-23 | Pronova Biopharma Norge As | Compositions and preconcentrates comprising at least one salicylate and omega-3 fatty acid oil mixture |
CN104306383A (en) | 2014-09-22 | 2015-01-28 | 广州市赛健生物科技有限公司 | Phosphatide soft capsule and preparation method thereof |
WO2015142705A1 (en) | 2014-03-18 | 2015-09-24 | U.S. Nutraceuticals, Llc D/B/A Valensa International | Composition and method to alleviate joint pain using algae based oils |
US20170182074A1 (en) | 2014-02-12 | 2017-06-29 | Aker Biomarine Antarctic As | Liquid phospholipid-containing compositions for the preparation of pharmaceuticals |
CN108265090A (en) | 2016-12-30 | 2018-07-10 | 中粮集团有限公司 | The preparation method of antarctic krill oil substitute |
-
2021
- 2021-02-04 WO PCT/EP2021/052702 patent/WO2021156385A1/en active Application Filing
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090074857A1 (en) | 2003-10-22 | 2009-03-19 | Enzymotec Ltd. | Glycerophospholipids for the improvement of cognitive functions |
WO2008068276A1 (en) | 2006-12-06 | 2008-06-12 | Ibsa Institut Biochimique S.A. | Soft gelatin capsules comprising acetylsalicylic acid |
WO2013072767A1 (en) | 2011-11-18 | 2013-05-23 | Pronova Biopharma Norge As | Compositions and preconcentrates comprising at least one salicylate and omega-3 fatty acid oil mixture |
US20170182074A1 (en) | 2014-02-12 | 2017-06-29 | Aker Biomarine Antarctic As | Liquid phospholipid-containing compositions for the preparation of pharmaceuticals |
WO2015142705A1 (en) | 2014-03-18 | 2015-09-24 | U.S. Nutraceuticals, Llc D/B/A Valensa International | Composition and method to alleviate joint pain using algae based oils |
CN104306383A (en) | 2014-09-22 | 2015-01-28 | 广州市赛健生物科技有限公司 | Phosphatide soft capsule and preparation method thereof |
CN108265090A (en) | 2016-12-30 | 2018-07-10 | 中粮集团有限公司 | The preparation method of antarctic krill oil substitute |
Non-Patent Citations (6)
Title |
---|
BHATT ET AL.: "Cardiovascular Risk Reduction with icosapent Ethyl for Hypertriglyceridemia", NEW ENGLAND JOURNAL OF MEDICINE, vol. 380, 2019, pages 11 - 22 |
DAN XIE ET AL.: "Antarctic Krill (Euphausia superba) Oil: A Comprehensive Review of Chemical Composition, Extraction Technologies, Health Benefits, and Current Applications", COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY, vol. 18, 2019, pages 514 - 534, XP055732800, DOI: 10.1111/1541-4337.12427 |
LIPOID GMBH: "Research Disclosure", vol. 527, KENNETH MASON PUBLICATIONS, article "Water soluble composition containing omega-3-fatty acids for use in dietetics and food" |
LIPOID GMBH: "Water soluble composition containing [omega]-3-fatty acids for use in dietetics and food", RESEARCH DISCLOSURE, KENNETH MASON PUBLICATIONS, HAMPSHIRE, UK, GB, vol. 527, no. 13, 1 March 2008 (2008-03-01), pages 211, XP007138010, ISSN: 0374-4353 * |
PATIL ET AL.: "Extraction and purification of phosphatidylcholine from soyabean lecithin", SEPARATION AND PURIFICATION TECHNOLOGY, vol. 75, 2010, pages 138 - 144, XP027322837 |
PATIL V V ET AL: "Extraction and purification of phosphatidylcholine from soyabean lecithin", SEPARATION AND PURIFICATION TECHNOLOGY, ELSEVIER SCIENCE, AMSTERDAM, NL, vol. 75, no. 2, 13 October 2010 (2010-10-13), pages 138 - 144, XP027322837, ISSN: 1383-5866, [retrieved on 20100814] * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023126026A3 (en) * | 2021-12-29 | 2023-08-24 | 中国科学院上海药物研究所 | Epa-ee lipid nanocomposite, formulation thereof, preparation method therefor, and application thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Stuchlík et al. | Lipid-based vehicle for oral drug delivery | |
US10188624B2 (en) | Enteric soft capsules comprising polyunsaturated fatty acids | |
US8410181B2 (en) | Omega-3 diglyceride emulsions | |
US20070122452A1 (en) | Fat composition | |
US20110262534A1 (en) | polysaccharide capsule enclosing a fatty acid oil-containing emulsion | |
JP5820256B2 (en) | Self-emulsifying formulation | |
AU2013264466B2 (en) | Improved complexes and compositions containing curcumin | |
CN102215839B (en) | Fat emulsion for the intensive care patient of artificial feeding grave illness | |
KR20060126678A (en) | Fat composition containing phospholipid and long-chain polyunsaturated fatty acid supplying compound and food using the same | |
JP2011012003A (en) | Emulsion composition for soft capsule and soft capsule | |
JP2006083136A (en) | Composition having action for preventing or ameliorating lowering of cerebral function caused by stress and symptom or disease involving the same lowering | |
WO2021156385A1 (en) | Lipid composition comprising omega-3 fatty acids | |
JP4522075B2 (en) | Composition having an effect of preventing or ameliorating symptoms or diseases caused by aging of blood vessels | |
KR20160144388A (en) | Composition and method to alleviate joint pain using low molecular weight hyaluronic acid and astaxanthin | |
CN101194919A (en) | Hippophae rhamnoides seed oil fatty milk injection and technique of preparing the same | |
JP5847475B2 (en) | Oil-containing composition and oral preparation containing the same | |
JP2005206789A (en) | New oil and fat composition | |
KR20160134787A (en) | Composition and method to alleviate joint pain using phospholipids and astaxanthin | |
JP7367275B2 (en) | oily composition | |
JP5221114B2 (en) | Soft capsule | |
JP2023069411A (en) | Agent for promoting absorption of lipid-soluble minor component | |
CN104095241A (en) | Marine animal phospholipid soft capsule and preparation method thereof | |
CN103040914A (en) | Preparation method of eucommia ulmoides seed oil nano emulsion injection | |
CN108402466A (en) | Vegetarian diet composition containing unsaturated fatty acid | |
JP2009219500A (en) | Composition for preventing or improving symptom or disease caused by ageing of blood vessel |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21702683 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21702683 Country of ref document: EP Kind code of ref document: A1 |