CA2199640A1 - Finely dispersed carotenoid and retinoid suspensions and their preparation - Google Patents
Finely dispersed carotenoid and retinoid suspensions and their preparationInfo
- Publication number
- CA2199640A1 CA2199640A1 CA002199640A CA2199640A CA2199640A1 CA 2199640 A1 CA2199640 A1 CA 2199640A1 CA 002199640 A CA002199640 A CA 002199640A CA 2199640 A CA2199640 A CA 2199640A CA 2199640 A1 CA2199640 A1 CA 2199640A1
- Authority
- CA
- Canada
- Prior art keywords
- carotenoid
- retinoid
- suspension
- water
- emulsifier
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 235000021466 carotenoid Nutrition 0.000 title claims abstract description 76
- 150000001747 carotenoids Chemical class 0.000 title claims abstract description 76
- 150000004492 retinoid derivatives Chemical class 0.000 title claims abstract description 69
- 239000000725 suspension Substances 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title description 2
- 238000002156 mixing Methods 0.000 claims abstract description 41
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 29
- 239000003960 organic solvent Substances 0.000 claims abstract description 26
- 239000012736 aqueous medium Substances 0.000 claims abstract description 19
- 239000000084 colloidal system Substances 0.000 claims abstract description 12
- 230000001681 protective effect Effects 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims description 33
- 239000000787 lecithin Substances 0.000 claims description 30
- 235000010445 lecithin Nutrition 0.000 claims description 30
- 229940067606 lecithin Drugs 0.000 claims description 28
- 239000002904 solvent Substances 0.000 claims description 28
- 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 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 239000000194 fatty acid Substances 0.000 claims description 24
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 20
- 229930195729 fatty acid Natural products 0.000 claims description 20
- 239000002245 particle Substances 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- -1 fatty acid salt Chemical class 0.000 claims description 10
- 150000007513 acids Chemical class 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 229960001295 tocopherol Drugs 0.000 claims description 8
- 239000011732 tocopherol Substances 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 239000003963 antioxidant agent Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 235000013305 food Nutrition 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000002609 medium Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims description 3
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims description 3
- 235000013361 beverage Nutrition 0.000 claims description 3
- 235000013399 edible fruits Nutrition 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- BMRWNKZVCUKKSR-UHFFFAOYSA-N butane-1,2-diol Chemical compound CCC(O)CO BMRWNKZVCUKKSR-UHFFFAOYSA-N 0.000 claims description 2
- 239000003086 colorant Substances 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 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 claims 2
- 229920000223 polyglycerol Polymers 0.000 claims 2
- 235000010384 tocopherol Nutrition 0.000 claims 2
- 229930003799 tocopherol Natural products 0.000 claims 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 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 claims 2
- FENFUOGYJVOCRY-UHFFFAOYSA-N 1-propoxypropan-2-ol Chemical compound CCCOCC(C)O FENFUOGYJVOCRY-UHFFFAOYSA-N 0.000 claims 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- 150000003626 triacylglycerols Chemical class 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 description 26
- 239000000243 solution Substances 0.000 description 24
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 15
- 150000001746 carotenes Chemical class 0.000 description 15
- 235000005473 carotenes Nutrition 0.000 description 15
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 15
- 150000004665 fatty acids Chemical class 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000008033 biological extinction Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003921 particle size analysis Methods 0.000 description 5
- 238000004040 coloring Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- HFJHNGKIVAKCIW-UHFFFAOYSA-N Stearyl monoglyceridyl citrate Chemical compound OCC(O)CO.OC(=O)CC(O)(CC(O)=O)CC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O HFJHNGKIVAKCIW-UHFFFAOYSA-N 0.000 description 2
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 2
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 229960004592 isopropanol Drugs 0.000 description 2
- 235000020778 linoleic acid Nutrition 0.000 description 2
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 2
- 229960004488 linolenic acid Drugs 0.000 description 2
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- RAFGELQLHMBRHD-VFYVRILKSA-N Bixin Natural products COC(=O)C=CC(=C/C=C/C(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C(=O)O)/C)C RAFGELQLHMBRHD-VFYVRILKSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000004258 Ethoxyquin Substances 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 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
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 101100321409 Rattus norvegicus Zdhhc23 gene Proteins 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- RAFGELQLHMBRHD-UHFFFAOYSA-N alpha-Fuc-(1-2)-beta-Gal-(1-3)-(beta-GlcNAc-(1-6))-GalNAc-ol Natural products COC(=O)C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC(O)=O RAFGELQLHMBRHD-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000001670 anatto Substances 0.000 description 1
- 235000012665 annatto Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- RAFGELQLHMBRHD-SLEZCNMESA-N bixin Chemical compound COC(=O)\C=C\C(\C)=C/C=C/C(/C)=C/C=C/C=C(\C)/C=C/C=C(\C)/C=C/C(O)=O RAFGELQLHMBRHD-SLEZCNMESA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- DECIPOUIJURFOJ-UHFFFAOYSA-N ethoxyquin Chemical compound N1C(C)(C)C=C(C)C2=CC(OCC)=CC=C21 DECIPOUIJURFOJ-UHFFFAOYSA-N 0.000 description 1
- 235000019285 ethoxyquin Nutrition 0.000 description 1
- 229940093500 ethoxyquin Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000000989 food dye Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 235000012680 lutein Nutrition 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
- 229960005375 lutein Drugs 0.000 description 1
- 239000001656 lutein Substances 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
- 239000000155 melt Substances 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 125000002678 retinoid group Chemical group 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000005471 saturated fatty acid group Chemical group 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000979 synthetic dye Substances 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
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/24—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene
-
- 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
- A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
- A23L5/40—Colouring or decolouring of foods
- A23L5/42—Addition of dyes or pigments, e.g. in combination with optical brighteners
- A23L5/43—Addition of dyes or pigments, e.g. in combination with optical brighteners using naturally occurring organic dyes or pigments, their artificial duplicates or their derivatives
- A23L5/44—Addition of dyes or pigments, e.g. in combination with optical brighteners using naturally occurring organic dyes or pigments, their artificial duplicates or their derivatives using carotenoids or xanthophylls
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B61/00—Dyes of natural origin prepared from natural sources, e.g. vegetable sources
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
- C09B67/0071—Process features in the making of dyestuff preparations; Dehydrating agents; Dispersing agents; Dustfree compositions
- C09B67/0084—Dispersions of dyes
- C09B67/0091—Process features in the making of dispersions, e.g. ultrasonics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
Abstract
Finely dispersed carotenoid or retinoid suspensions are prepared by dissolving the carotenoid or retinoid is a volatile, water-miscible organic solvent at 50°C-250°C, where appropriate under elevated pressure, within less than 10 sec and immediately thereafter mixing the solution with an aqueous medium at from 0 to 90°C, wherein the mixing with the aqueous medium takes place in the absence of a protective colloid and in the presence of at least one physiologically tolerated emulsifier.
Description
2~ qq6~
-Finely dispersed ~ ' and retinoid o and their I ~, _ The invention relates to finely dispersed carotenoid and retinoid ., ~ which can be used, for example, for coloring human and 15 animal foods, and to a process for their ~
Carotenoids are pigments with a yellow to red color which are wides-pread in nature. They confer a ~ ;. coloring on many foodstuffs.
Important 1~ of the class of c.llut~ Jid~ are ~-carotene"~-apo-20 8'-carotenal, i and l ' These dyes can be prepared by synthesis and can be used as substitutes for synthetic dyes for coloring human and animal foods. They are additionally used in the 1' irldustry, for example because of their pro vitamin A activity.
25 In order to be; .~cyd~l~ as dyes in human and animal foods arld in the ,uh~ industry, the ~.uot~lloid~ and retinoids must be in a finely dispersed form because they are insoluble in water and have only low solubility in fats and oils. In addition, calut~.loid~ and retirloids are very serlsitive to oxidation.
Various processes for preparing finely dispersed c~ut~.~ùid~ and retinoids are known.
2 1 li) ,J ~; ~r O
In US 5,091,188 and 5,091,187 ~ !;pil-coated u~ s are des-cribed which are fnrm-ll of water insoluble ~ 1, I com-pounds which can be injected. A number of water insoluble 1' -cal -----r- ', e.g. OJ~J~ ld~ (OTC), I,.ylllll ~, , slh~m197nl 5 " ~ ' or ~1' l are formed in a dispersion of fine particles by using ~ s like lecithin. Among the processes suggested for the Liull of the dispersions is the solvent dilution wherein solutions of the lipid and water-insoluble drug are prepared in an organic solvent like ethanol which is miscible with water. The solutions are expressed into an o aqueous medium with high agitation, leaving behirld the drug in micro-crystaline form. The use of ~rlulillv;d~i, or retinoides is not disclosed.
EP-B-0 065 193 describes a process for preparing finely dispersed carotenoid and retinoid products in powder form, wherein the carotenoid 15 or retinoid is dissolved in a volatile, water-miscible, organic solvent at from 50~C to 200~C, where .~ under elevated pressure, within less than 10 sec, the carotenoid is " '~ 1'1' . ' in the form of a colloidal dispersion from the resulting molecular solution by rapid mixing with an aqueous solution of a swellable colloid at from 0~C to 20 50~C~ and the solvent and the dispersing medium are removed from the resulting dispersion in a .. ~ ' way. Besides a swellable colloid, it is possible to employ a plastici~er and, where ..~,1,1~, , stabili~ers.
Lecithin is mentioned as stabili~er which can be used. It is stated that the degree of fineness can be controlled by the choice of the stabili~ers added 25 to the carotenoid solution.
EP-A-0 479 066 discloses a process for the continuous ~1,, of ~-carotene ' ' " by heating ~-carotene together with an emulsifier until it dissolves, cooling the !~ solution to below 100~C by adding water and ~ , adjusting the requ~red f~l ~ I YY640 rrf~lciflfrc stated to be usable are clllu~.y' ' lli61.~ i~s of fatty acids, c~hu~-y' ' sorbitan fatty acid esters and C~lU~y' ' ll~v~lul~Jdlu~y fatty acids. The ,B-carotene is heated together with the emulsifler for from 17 to 68 sec. The s~' ' ' contain no protective colloid.
EP-0 û55 817 describes a process for preparing stable injectable ~-carotene ~ l To do this, an emulsifier is heated to from 160 to 180~C, and ,~-carotene is introduced into the melt over about S mmutes.
After the ,B-carotene has dissolved, water is added to the solution, and it ~o is cooled to from 60 to 80~C, resulting in the ' ' ' r. .I~:r,. . ~
statcd to be usable are cillw~y' ~ Cs of fatty acids, el~lu~y' ~ ' sorbitan fatty acid esters and ClllU~.y' ' ~ lU/~y fatty acids. The -' ' ' contain no protective colloid.
15 It is an object of the present invention to provide finely dispersed carotenoid and retinoid . in which it is possible to dispense with a protective colloid, and a process for their ~cy It is another object of the present invention to provide a process for 20 preparing fmely dispersed carotenoid and retinoid ~ . in which the .~ut.l,ui.lD or retinoids are treated under mild conditions.
It is another object of the present invention to provide finely dispersed carotenoid and retinoid: -r ~ which are ~h~ ,;ol~ dlly acceptable, 25 and a process for their ~ ~d~iUI~.
It is another object of the present invention to provide finely dispersed carotenoid and retinoid , ~ and a process for their ~ ,pol~liul-~ it being possible to vary the color of the resulting ~
- 2 1 9964~
-Finely dispersed ~ ' and retinoid o and their I ~, _ The invention relates to finely dispersed carotenoid and retinoid ., ~ which can be used, for example, for coloring human and 15 animal foods, and to a process for their ~
Carotenoids are pigments with a yellow to red color which are wides-pread in nature. They confer a ~ ;. coloring on many foodstuffs.
Important 1~ of the class of c.llut~ Jid~ are ~-carotene"~-apo-20 8'-carotenal, i and l ' These dyes can be prepared by synthesis and can be used as substitutes for synthetic dyes for coloring human and animal foods. They are additionally used in the 1' irldustry, for example because of their pro vitamin A activity.
25 In order to be; .~cyd~l~ as dyes in human and animal foods arld in the ,uh~ industry, the ~.uot~lloid~ and retinoids must be in a finely dispersed form because they are insoluble in water and have only low solubility in fats and oils. In addition, calut~.loid~ and retirloids are very serlsitive to oxidation.
Various processes for preparing finely dispersed c~ut~.~ùid~ and retinoids are known.
2 1 li) ,J ~; ~r O
In US 5,091,188 and 5,091,187 ~ !;pil-coated u~ s are des-cribed which are fnrm-ll of water insoluble ~ 1, I com-pounds which can be injected. A number of water insoluble 1' -cal -----r- ', e.g. OJ~J~ ld~ (OTC), I,.ylllll ~, , slh~m197nl 5 " ~ ' or ~1' l are formed in a dispersion of fine particles by using ~ s like lecithin. Among the processes suggested for the Liull of the dispersions is the solvent dilution wherein solutions of the lipid and water-insoluble drug are prepared in an organic solvent like ethanol which is miscible with water. The solutions are expressed into an o aqueous medium with high agitation, leaving behirld the drug in micro-crystaline form. The use of ~rlulillv;d~i, or retinoides is not disclosed.
EP-B-0 065 193 describes a process for preparing finely dispersed carotenoid and retinoid products in powder form, wherein the carotenoid 15 or retinoid is dissolved in a volatile, water-miscible, organic solvent at from 50~C to 200~C, where .~ under elevated pressure, within less than 10 sec, the carotenoid is " '~ 1'1' . ' in the form of a colloidal dispersion from the resulting molecular solution by rapid mixing with an aqueous solution of a swellable colloid at from 0~C to 20 50~C~ and the solvent and the dispersing medium are removed from the resulting dispersion in a .. ~ ' way. Besides a swellable colloid, it is possible to employ a plastici~er and, where ..~,1,1~, , stabili~ers.
Lecithin is mentioned as stabili~er which can be used. It is stated that the degree of fineness can be controlled by the choice of the stabili~ers added 25 to the carotenoid solution.
EP-A-0 479 066 discloses a process for the continuous ~1,, of ~-carotene ' ' " by heating ~-carotene together with an emulsifier until it dissolves, cooling the !~ solution to below 100~C by adding water and ~ , adjusting the requ~red f~l ~ I YY640 rrf~lciflfrc stated to be usable are clllu~.y' ' lli61.~ i~s of fatty acids, c~hu~-y' ' sorbitan fatty acid esters and C~lU~y' ' ll~v~lul~Jdlu~y fatty acids. The ,B-carotene is heated together with the emulsifler for from 17 to 68 sec. The s~' ' ' contain no protective colloid.
EP-0 û55 817 describes a process for preparing stable injectable ~-carotene ~ l To do this, an emulsifier is heated to from 160 to 180~C, and ,~-carotene is introduced into the melt over about S mmutes.
After the ,B-carotene has dissolved, water is added to the solution, and it ~o is cooled to from 60 to 80~C, resulting in the ' ' ' r. .I~:r,. . ~
statcd to be usable are cillw~y' ~ Cs of fatty acids, el~lu~y' ~ ' sorbitan fatty acid esters and ClllU~.y' ' ~ lU/~y fatty acids. The -' ' ' contain no protective colloid.
15 It is an object of the present invention to provide finely dispersed carotenoid and retinoid . in which it is possible to dispense with a protective colloid, and a process for their ~cy It is another object of the present invention to provide a process for 20 preparing fmely dispersed carotenoid and retinoid ~ . in which the .~ut.l,ui.lD or retinoids are treated under mild conditions.
It is another object of the present invention to provide finely dispersed carotenoid and retinoid: -r ~ which are ~h~ ,;ol~ dlly acceptable, 25 and a process for their ~ ~d~iUI~.
It is another object of the present invention to provide finely dispersed carotenoid and retinoid , ~ and a process for their ~ ,pol~liul-~ it being possible to vary the color of the resulting ~
- 2 1 9964~
It is another object of the present invention to provide finely dispersed carotenoid and retinoid . which have a high content of active ingredient and low viscosity, and a process for their ~,...
5 We have found that these objects are achieved according to the invention by ~ and processes as described below.
CAROTENOIDS AND RE~NOIDS
~o The process according to the invention is preferably used to prepare finely dispersed carotenoid and retinoid Examples of ~ut~ ;d~ which can be used according to the invention are the known, available, natural or synthetic ~ c~c.~ of this class of 15 ~ . ', for exarnple carotene, Iycopene, bixin, ' .
~l y,ut~....lfill" ' lutein" ' ' 2 ' " ' , ,1~-apo-4'-carotenal, ,~-apo-8'-carotenal, ,B-apo-12'-carotenal, ,B-apo-8'-carotenoic acid and esters of hydroxyl- or carboxyl-containing ~ of this group, for example lower alkyl esters, prefeMbly methyl and etbyl esters. These 20 . ._ ' can be used, for example, very .;~r.~,,,;ly as coloring agents. The ' "~, obtainable IC~ such as ,~-carotene, ~- apo-8'-carotenal and ~-apo-8'-carotenoic esters are ~i ' '~, preferred.
25 It is likewise possible to use retinoids, for example all-tr~ hl~ic acid, 13-cis-retinoic acid and the esters and amides of these acids. C
of this type which can be used are described by D.L. Newton, W.R.
Henderson and M.B. Sporn in Cancer Research 40, (1980) 3413-3425.
2 i '~9640 SOLVENTS
A water-miscible organic solvent in which the c~ut.,ll~Jid~ or retinoids employed are soluble at elevated i . .; is used in the process 5 according to the invention Every suitable solvent can be used according to the invention, and preferably water-miscible, thermally stable, volatile solvents containing only carbon, hydrogen and oxygen are used. Examples of suitable solvents are alcohols, ethers, esters, ketones and acetals and mixtures ttlereof. Preferably used are ethanol, n-propanol, ~
o 1,2-butanediol 1-methyl ether, 1,2-~...r " ' 1-n-propyl ether or acetone, or a mixture of two or more thereof.
Solvents which are preferably used are those whose miscibility with water is at least 10% by volume, which have a boiling point below 200~C and, 15 where ~IIU~I- ', have fewer than 10 carbon atoms in their structure.
The carotenoid or retinoid is, in one ' " of the invention, employed in the dissolving in the form of a suspension in a volatile, water-miscible organic diluent or solvent, preferably in the solvent used in 20 the dissolving, as described above.
I:'tl~Oi~10~ .11y tolerated emulsifiers can be employed according to the~5 invention for preparing the finely dispersed carotenoid and retinoid according to the invention.
The term "~ Diol~ lly tolerated" means in this connection that the emulsifiers are Aut.~i,ioloL "~ acceptable on r' ~ ' ' " in the usual 30 amounts to humans or animals and do not result in harrn to the body.
2 ~ 9~
CAROTENOIDS AND RE~NOIDS
~o The process according to the invention is preferably used to prepare finely dispersed carotenoid and retinoid Examples of ~ut~ ;d~ which can be used according to the invention are the known, available, natural or synthetic ~ c~c.~ of this class of 15 ~ . ', for exarnple carotene, Iycopene, bixin, ' .
~l y,ut~....lfill" ' lutein" ' ' 2 ' " ' , ,1~-apo-4'-carotenal, ,~-apo-8'-carotenal, ,B-apo-12'-carotenal, ,B-apo-8'-carotenoic acid and esters of hydroxyl- or carboxyl-containing ~ of this group, for example lower alkyl esters, prefeMbly methyl and etbyl esters. These 20 . ._ ' can be used, for example, very .;~r.~,,,;ly as coloring agents. The ' "~, obtainable IC~ such as ,~-carotene, ~- apo-8'-carotenal and ~-apo-8'-carotenoic esters are ~i ' '~, preferred.
25 It is likewise possible to use retinoids, for example all-tr~ hl~ic acid, 13-cis-retinoic acid and the esters and amides of these acids. C
of this type which can be used are described by D.L. Newton, W.R.
Henderson and M.B. Sporn in Cancer Research 40, (1980) 3413-3425.
2 i '~9640 SOLVENTS
A water-miscible organic solvent in which the c~ut.,ll~Jid~ or retinoids employed are soluble at elevated i . .; is used in the process 5 according to the invention Every suitable solvent can be used according to the invention, and preferably water-miscible, thermally stable, volatile solvents containing only carbon, hydrogen and oxygen are used. Examples of suitable solvents are alcohols, ethers, esters, ketones and acetals and mixtures ttlereof. Preferably used are ethanol, n-propanol, ~
o 1,2-butanediol 1-methyl ether, 1,2-~...r " ' 1-n-propyl ether or acetone, or a mixture of two or more thereof.
Solvents which are preferably used are those whose miscibility with water is at least 10% by volume, which have a boiling point below 200~C and, 15 where ~IIU~I- ', have fewer than 10 carbon atoms in their structure.
The carotenoid or retinoid is, in one ' " of the invention, employed in the dissolving in the form of a suspension in a volatile, water-miscible organic diluent or solvent, preferably in the solvent used in 20 the dissolving, as described above.
I:'tl~Oi~10~ .11y tolerated emulsifiers can be employed according to the~5 invention for preparing the finely dispersed carotenoid and retinoid according to the invention.
The term "~ Diol~ lly tolerated" means in this connection that the emulsifiers are Aut.~i,ioloL "~ acceptable on r' ~ ' ' " in the usual 30 amounts to humans or animals and do not result in harrn to the body.
2 ~ 9~
This applies in particular to oral or ' a~ fi~ Liùll.
r ~ ~ which can be used according to the invention are listed hereinafter.
In a preferred ~c" of the invention, lecithin can be employed as emulsifier to prepare the finely dispersed carotenoid and retinoid according to the invention. Lecithins are also known under the name I' ,' '~I~,I.ùli~i, and belong to the group of o ~ .' .' 'i, ' formed from fatty acids, glycerol, phosphoric acid and choline by .~t~,lir ' All suitable pl~v~ ' ' ' can be used according to the invention, especially the naturally occurring ~I.v~JLlid~ ' " , which are 15 derivatives of 1,2-diacyl-sn-glycerol-3-phosphoric acids. It is possible to use ,UIlU~ ' " with identical or different fatty acid residues, and mixtures thereof.
A lecithin fraction from soybeans contains, for example, fatty acid 20 residues from palmitic acid, stearic acid, l l ' ~ acid, oleic acid, linoleic acid and linolenic acid.
It is possible to employ l' .' '~,' ' " with both ~ ' and saturated fatty acid residues.
In a ~,~i ' '~, preferred ~ ' ' of the invention, partially hydrolyzed lecithins are used to prepare the finely dispersed carotenoid and retinoid . according to the invention, especially those which have a l~v~ l content of 10-15% by weight. One example of a 30 lecithin or lecithin mixture of this type is Emulfluid~ E from Lucas 7 2~ q(Jl~4[~
Meyer GmbH.
In one ' ' of the invention, a mono-, di- or l-i61y~c~i~1~ of an aliphatic di- or puly~ )v~.ylic acid can be employed as emulsifier to 5 prepare the finely dispersed carotenoid and retinoid . according to the invention. The di- or polyc.~ v~ylic acid may have hydroxyl groups which are l ' ' or substituted by acetyl radicals. Examples of acids which can be used are citric acid or tartaric acid. Examples of acid glycerides which can be used are citric esters of a mono- or o diglyceride (for example Acidan N12~ from Grinstedt), and v;~ ,lyllall.ui~, esters of o~y~,liv~.~ (DATEM, for example Panodan TR0 from Grinstedt).
In one l,.~lbC' of the invention, a sugar fatty acid ester can be 15 employed as emulsifier to prepare the finely dispersed carotenoid and retinoid . ~ according to the invention. It is possible in this case to use plly~;ulvOic~llly tolerated fatty acids such as lauric acid, palmitic acid, stearic acid or mono- or pC,lJ, ' fatty acids such as linoleic acid or linolenic acid. The sugar residue can be any suitable sugar 20 residue, preferably an ascorbyl radical. One example of a sugar fatty acid ester which can be used is ascorbyl palmitate.
It is r j~ C possible to use the emulsifiers as described, for example, in EP-A-0 479 066 or EP-A-0 055 817.
It is r 1~ C possible to use salts of ~Jh~..;vlO6;~.ally tolerated fatty acids as described above, and mono- and v;Oly~,e~idc~ of these fatty acids.
The mono- and di61y-,c.i~ of these fatty acids may, where a be esterifled with fruit acids.
2 1 ) 'i6 ~0 In one r~ of the invention, it is r ih~ lvl~ possible to use i~VI~lY~,Iul esters of these fatty acids.
Lecithin is preferably employed as emulsifier to prepare the finely 5 dispersed carotenoid and retinoid r ' according to the invention.
The emulsifiers which can be used according to the invention, especially lecithin, are 1' ~Divlv~ ally acceptable and can thus be used in .. . ...
It has r~ ,ll..ol~ been found according to the invention that the emulsifiers which can be used according to the invention, especially the lecithin which is used in one i. b~" t, have a very fast ~
action, wilich makes it possible to use them in a high-speed process for i5 preparing finely dispersed carotenoid and retinoid It has been found according to the invention that it is possible to dispense with the use of a protective colloid on use of the emulsifiers according to the invention, especially of lecithin, in the ~ . of 20 finely dispersed carotenoid and retinoid , The omission of a protective colloid leads to liquid carotenoid and retinoid ~ - witb a lower viscosity and a higher content of active ingredient. In addition, especially for yl~ ' ~p~ the number of ingredients in tbe . . is reduced, so that fewer interfering . . ' which may 25 have an effect on the activity of the cDlut~NidD and/or retinoids are present.
The emulsifier used according to the invention, especially tile lecitbin, can in the process according to the mvention be present in the aqueous 30 medium and/or in the organic solvent. rrhus, the emulsifier used accdirlg 2 ~
.9.
to the invention, especially the lecithin, can be present either in the cllcr~nci. prepared before the dissolving, of the carotenoid in the water-miscible organic solvent, or ~ in the water-miscible organic solvent which is at elevated t~ d~ . The emulsifier used according to 5 the invention, especially the lecithin, is preferably added both to the organic carotenoid and retinoid suspension and to the aqueous medium.
The ratio of the amounts of emulsifier used according to the invention,especially lecit~un, to carotenoid or retinoid can be chosen as desired, as o long as f~nely dispersed carotenoid and retinoid . ~ which are stable are obtained.
The ratio of emulsifier used according to the invention, especially of lecithin, to carotenoid or retinoid in the suspension is preferably from 0.1 15 to 5 (ratio of the parts by weight). The ratio is ~ , preferably 0.5 to 2, in particular 0.7 to 1.
It is r '~ ~ possible to change the color of the resulting carotenoid and retinoid . by changing the ratio of amounts of emulsifier 20 used according to the invention, especially lecithin, to carotenoid or retinoid. With high ~)IUpUli- of emulsifier used according to the invention, especially lecithin, for example with a ratio of 2:1 by weight of emulsifier used according to the invention, especially lecithin, to carotene, the resulting products tend to be yellowish, and in the case of 25 carotene and lecithin as emulsifier the latter is at least partially dissolved in the lecithin. With lower ~IU,UUIi- of emulsifler used according to the invention, especially lecithin, relative to carotenoid, such as 0.75:1, for example ~-carotene remains particulate. The color of the suspension is reddish brown in this case.
~ 1 996~
~ o This variability of the color is ~ for use of the carotenoid and retinoid . of the present invention as food dye because it is simple to adapt the color depending on the specific use.
5 r, l1I~IIIUIC, the omission of protective colloids in the carotenoid and retinoid . makes it possible to prepare low-viscosity . .
with high contents of active ingredient, for example of up to 10% by weight based on the finished . . This simplifies the use and the transport of the ~ . because even with high contents of active ingredient they are still able to flow and be metered . ~ rA. ~
For example, this simplifies the use of ~-carotene in the coloring of beverages because liquid metering devices can be used, which generally operate more precisely than solid metering devices in ~ ~
15 plants.
Another advantage of the omission of protective colloids is that the can be used better in 1' ' ~ For example, the . . prepared according to the invention can be used 20 as injection solutions, for example in veterinary medicine.
ANTIOXIDANTS
An antioxidant can be added in the process according to the invention to 25 the water-miscible organic solvent or to the aqueous medium, to the finished suspension of the carotenoid or retinoid and to the ~vt~,~v;J~
and retinoids. The Pntio~ is used to increase the stability of the active ingredient to oxidative breakdown. The ' if used is preferably dissolved together with the ~lut~ id~ or retinoids in the 30 water-miscible organic solvent. Examples of ' ' which can be 2 1 ~640 "
used are ~x-tocopherol, t-~uLylh~lu~y~ulu~, t-bu~ylll~llu~.y,~ vl~ or ethoxyquin. Other suitable ' can also be used.
PREPARATION PROCESS
The carotenoid and retinoid . are prepared according to the invention by dissolving the carotenoid or retinoid in a volatile, water-miscible organic solvent at from 50~C to 250~C, preferably 150 to 200~C, where ~ . under elevated pressure, within less than 10 o sec, and " l~, thereafter mixing the solution with an aqueous medium at from 0 to 90~C, preferably 2-50~C. A procedure of this type is described, for example, in EP-B1-0 065 193. The process described in this patent can be used according to the present invention.
~5 The emulsifler used according to the invention can be present in the aqueous medium and/or in the organic diluent or solvent. The emulsifier, preferably lecithin, is preferably present in the aqueous medium and in the organic diluent or solvent.
20 In one ~ L " of the invention, the emulsifler used according to the invention, preferably lecithin, is added to the water-miscible organic solvent used to prepare the initial suspension of the carotenoid or retinoid, as well as to the aqueous medium, preferably water.
25 If required, the emulsifler used according to the invention can also be present m the heated organic solvent.
Then, in one ~ ~ " of the invention, a suspension of the carotenoid or retinoid in the water-miscible organic solvent is prepared. The water-30 miscible organic solvent used is preferably the same as is used as heated - 12 - 2 ~ 6 4 0 organic solvent in the subsequent step. In one ~ L ' of the invention, the . of the carotenoid or retinoid in this suspension is 2 to 40% by weight, based on the mixture. This suspension or the carotenoid or retinoid is then, in one ~ '~" of the invention, 5 dissolved in heated water-miscible organic solvent within less than 10 sec, preferably less than 5 sec, p~il,ul.~ly preferably less than 2 sec, in particular in fractions of asecond. In this case, heaeed solvent is at from S0 to 200~C, preferably 100 to 180~C, particularly preferably 140 to 180~C. After the time for dissolving the carotenoid or retinoid in the o heated water-miscible organic solvent, the solution is " 'y thereafter mixed with an aqueous medium, at from 0 to 50~C. Water is preferably used as aqueous medium. Mixing the solution with the aqueous medium results in a fine dispersion of the carotenoid or retinoid.
15 The very short time needed to dissolve the carotenoid or retinoid means that the carotenoid or retinoid is exposed to an elevated ~ for only a very short time and is then ~ , cooled again. This makes it possible for the ~ V~lVid~ and/or retinoids to be treated under very mild conditions, and reduces the risk of oxidation or ~' . of the 20 active ingredients. Compared with the process according to the invention, for example, when the active mgredient and solvent are heated together the carotenoid or retinoid is exposed to an elevated t~ tUl~ for a '' "y longer time until it dissolves, and this is associated with tbe risk of oxidation and/or thermal ~-- . of the active ingredient.
In a preferred . b~" of the invention, the process is carried out ' l~, in two mixing chambers. This entails first a suspension of the active ingredient in the organic solvent being prepared and, for example by means of pumps, being fed into a first mixing chamber, into 30 which the heated organic solvent is fed ' '~" so that the active - 2 1 ~ 4 0 ~ 13 -ingredient dissolves in the water-miscible organic solvent in the first mixing chamber at from 50 to 200~C. The active ingredient:
in this first mixing chamber is preferably 0.5 to 10% by weight based on the solution. The volume of the mixing chamber is preferably such that 5 the residence time of the active ingredient suspension and the solvent in the chamber is preferably less than l sec at the chosen delivery rate of the pumps.
The solvent is preferably brought to the required i , ~ by a heat o exchanger before enterjng the mixirlg chamber, while the active ingredient suspension is kept at below 50~C by being fed through a thermally insulated feed line. The mixing in the first mixing chamber is preferably turbulent. After a short residence time, preferably of less than 1 sec, the solution enters a second mixing chamber in which, for exarnple by a 15 pump, water or an aqueous medium is admixed, and the finely dispersed carotenoid and retinoid suspension is p~, 1. The finely dispersed active ingredient suspension can then be discharged from the second mixmg chamber through another line and fed, for example, into a reservoir. To maximize the active mgredient the suspension 20 can be circulated back to the second mixing chamber.
The: of the carotenoid or retinoid in the suspension is in this case preferably 0.1 to 100 g/l.
25 If the pressure exceeds 1 bar, solvents can be used at i . LS above their boiling point (under .' pressure).
In one e ' " of the invention, a product in powder form can be obtained from the resulting . ' for example by the process 30 described in D~A 2 534 091 by spray-drying or spray-cooling or by 21 9~6~0 enveloping the particles, removing and drying in a fluidized bed.
The spray-drying process is described, for example, also in EP-Bl-0 065193.
In one ~ ' " of the invention it is possible to remove, at least partially, the water-miscible organic solvent and/or the aqueous medium from the prepared carotenoid or retinoid . m order to prepare a ' carotenoid or retinoid r ' In this case, the ~o of the carotenoid or retinoid in the suspension can be 0.1 to 100 g/l.
It is possible by adjusting suitable quantity flows to obtain a carotenoid or retinoid suspension with a very small particle size of active ingredient.
15 The particle size in the carotenoid or retinoid suspension is essentially <
1 ~m, preferably in the range from 0.01 to 0.4 ~m, I,.ui ' '~, preferably in the range from 0.03 to 0.2 ~m.
It is possible, for example, to obtain a suspension with an average 20 particle size of active ingredient of 0.03 ~Lm at a carotene of 0.1% by weight based on the finished c~cr~-~;~-- In this case, the suspension has the appearance of a transparent carotene "solution". If the active ingredient content is higher, it is possible in one ~ " of the invention to increase tbe particle size. For example, it can average 25 0.06 ~m in a 0.4% by weight solution. It is possible by the resulting suspension to achieve an active ingredient content of from 1 to 10% by weight based on the finished ~,1 This can take place, for example, by C~l,UUlllliUI~ under mild conditions or by membrane filtration. The resulting . are stable on storage and have a 30 virtually unchanged high specific color strength. The orgaluc solvent 2 1 '7i C,~ 6 ~ ~
employed can, where dlJUIu~J , be removed from the product, depending on the ...~ ,l.,.l;.-~ step used. In a preferred; '-' t, iso-propanol or ethanol is used as solvent, and the carotenoid or retinoid is dissolved at about 180~C in an excess of preheated alcohol so that a 5 ~ 'g. ~ v--- solution is produced.
On mixing with water, which is the aqueous medium preferably used, the alcohol dissolves '~, in the water, resulting in an extremely funely disrersed suspension of the carotenoid or retinoid.
The invention is explained in detail hereinafter by means of an exemplary ;
12.5 g of ,B-carotene are dissolved in 490 g of a solution of 9 g of lecithin (Emulfluid0 E, Lucas Meyer GmbH, prepared by specific partial hydrolysis of natural lecithin, with a l~ .' .' Iiri~' content of 10-15%
by weight, an HLB of 8-9) and 1.8 g of d,l-~-tocopherol in i~v,ulu~
20 (azeotrope) and mixed in a first mixing chamber with 775 g of iav~lu~ vl (azeotrope) which has been heated to 220~C im a heat exchanger. At a metering rate of about 2 l/h for the suspension and 3 I/h for the heated solvent, the residence time in the mixing chamber is 0.35 sec. This results, at 190~C, in a molecular solution which is then 25 fed into a second mixing chamber in which it is subjected to turbulerlt mixing with 7800 g of water (metering rate about 30 l/h). This results in formation of the finely dispersed carotene -r ', which is transferred into a collecting vessel. A clear orange suspension of carotene is obtained in the collecting vessel. The of active ingredient in this case 30 is 0.1% by weight based on ~h fmished . and the specific 21 q9640 color strength (extinction at a path length of 1 cm at the maximum of the absorption band of a yl~ydld~iull diluted to an active ingredient cûntent of S ppm with water) is 0.72. Particle size analysis by photûn cûrrelation ~y~ lu~vyy reveals an average particle size ûf 70 nm.
EXAMrLE 2 120 g of ,i~-carotene are dissolved in 540 g of a sûlution of 43 g of lecithin (Emulfluid~ E, Lucas Meyer GmbH, see Example 1) and 17 g ûf d,l-~Y-tocopherol in isvy~uy~l~ol (azeotrope) and mixed in a first mixing chamber with 825 g of iDVyl~r ' (a2eotrope) which has been heated to 220~C in a heat exchanger. At a metering rate of about 2 I/h for the suspension and 3 I/h for the heated solvent, the residence time in the mixing chamber is 0.35 sec. This results, at 190~C, in a mûlecular sûlution which is then fed into a second mixing chamber in which it is subjected to turbulent mixing with 8800 g of a solution of 43 g of lecithin in 10,400 g of water (metering rate about 30 I/h). This results in formation of the finely dispersed carotene r"spPn~ , which is transferred into a collecting vessel. An orange suspension of carotene is obtained in 20 the collecting vessel. The . of active ingredient in this case is 1% by weight based on the finished . and the specific color strength (extinction at a path length of 1 cm at the maximum of the absorption band of a y.~, diluted to an active ingredient content of S ppm with water) is 0.67. Particle size analysis by photon correlation 25 ~y~,~,Llu~_uy,~ reveals an average particle size of 160 nm.
12.5 g of ,~-carotene are dissolved in 490 g of a solution of 1.8 g of 30 citric ester of a mono/diglyceride (Acidan N12~ from Grinstedt) and 1.8 .
~ ~ - 17--g of d,l-o~-tocopherol in i~v~,.,r ~' (azeotrope) and mixed in a first mixing chamber with 775 g of i~vylu~ ol (azeotrope) which has been heated to 220~C in a heat exchanger. At a metering rate of about 2 I/h for the suspension and 3 I/h for the heated solvent, the residence time in 5 the mixing chamber is 0.35 ~c. This results, at 190~C, in a molecular solution which is then fed into a second mixing chamber in which it is subjected to turbulent mixing with 7800 g of water (metering rate about 30 I/h). This results in formation of the finely dispersed carotene ., which is transferred into a collecting vessel. A clear orange~ suspension of carotene is obtained in the collecting vessel. The of active ingredient in this case is 0.1% by weight based on the finished il ~ and the specific color strength (extinction at a path length of 1 cm at the maximum of the absorption band of a ~lc~ un diluted to an active ingredient content of S ppm witb water) 15 is 0.66. Particle size analysis by photon correlation ~ V~,V~)y reveals an average particle size of 80 nm.
ExA~fpLE 4 20 25 g of ,~-carotene are dissolved in 950 g of a solution of 3.6 g of d;~ ,Lylkul~, ester of l~vllo~ wli~ (Panodan TR~ from Grinstedt) and 3.6 g of d,l-~-tocopherol in isv~, ' (azeotrope) and mixed in a first mixing chamber with 1300 g of i~u~,.,, I (azeotrope) which has been heated to 220~C in a heat exchanger. At a metering rate of about 2 I/h 25 for tne suspension and 3 I/h for the heated solvent, the residence time in the mixing chamber is 0.35 sec. This results, at 190~C, in a molecular solution which is then fed into a second mixing chamber in which it is subjected to turbulent mixing with 15,400 g of water (metering rate about 30 I/h). This results in formation of the finely disper~d carotene 30 , ~, which is transferred into a collecting vessel. A clear orange -18- 2~ ~q~
suspension of carotene is obtained in the collecting vessel The of active ingredient in this case is 0.14% by weight based on the finished . and the specific color strength (extinction at the maximum of the absorption band of a l)ICL~ diluted to an active 5 ingredient content of 5 ppm with water) is 0.72. Particle size analysis by photon correlation ~,IIU:~-,U~ reveals an average particle size of 220 nm.
25 g of ,B-carotene are dissolved in 290 g of a solution of 3.6 g of ascorbyl palmitate and 3.6 g of d,l-~-tocopherol in i~U~ r -' (azeotrope) and mixed in a first mixing chamber with 350 g of isopropanol (azeotrope) which has been heated to 220~C in a heat exchanger. At a 15 metering rate of about 2 I/h for the suspension and 3 I/h for the heated solvent, the residence time in the mixing chamber is 0.35 sec. This results, at 190~C, in a molecular solution which is then fed into a second mixing chamber in which it is subjected to turbulent mixing with 4150 g of water (metering rate about 30 I/h). This results in formatiûn 20 of the finely dispersed carotene , which is transferred into a collecting vessel. A clear orange suspension of carotene is obtained in the collecting vessel. The . of active ingredient in this case is 0.5% by weight based on the finished . ~, and the specific color strength (extinction at the maximum of the absorption band of a 25 ~ diluted to an active ingredient content of S ppm with water) is 0.69. Particle size analysis by photon correlation ~ ,LIU~,U~ reveals an average particle size of 120 nm.
The prepared . ' of ,~-carotene are l'~;.;UIU~ .dlly acceptable and 30 stable on storage for a long time. The ,B-carotene used in the IJI~r ~ -,9- 21 ~43 process is treated under very mild conditions because it is present in the heated solvent for only a very short time (0.35 seconds). The color of the finely dispersed carotenoid suspension varies because of the differences in particle size so that the color can be adjusted and varied depending on 5 the way the process is carried out. The carotenoid ~ r have a high active ingredient content and low viscositv so that dividing into portions is simple, for example in the production of beverages.
r ~ ~ which can be used according to the invention are listed hereinafter.
In a preferred ~c" of the invention, lecithin can be employed as emulsifier to prepare the finely dispersed carotenoid and retinoid according to the invention. Lecithins are also known under the name I' ,' '~I~,I.ùli~i, and belong to the group of o ~ .' .' 'i, ' formed from fatty acids, glycerol, phosphoric acid and choline by .~t~,lir ' All suitable pl~v~ ' ' ' can be used according to the invention, especially the naturally occurring ~I.v~JLlid~ ' " , which are 15 derivatives of 1,2-diacyl-sn-glycerol-3-phosphoric acids. It is possible to use ,UIlU~ ' " with identical or different fatty acid residues, and mixtures thereof.
A lecithin fraction from soybeans contains, for example, fatty acid 20 residues from palmitic acid, stearic acid, l l ' ~ acid, oleic acid, linoleic acid and linolenic acid.
It is possible to employ l' .' '~,' ' " with both ~ ' and saturated fatty acid residues.
In a ~,~i ' '~, preferred ~ ' ' of the invention, partially hydrolyzed lecithins are used to prepare the finely dispersed carotenoid and retinoid . according to the invention, especially those which have a l~v~ l content of 10-15% by weight. One example of a 30 lecithin or lecithin mixture of this type is Emulfluid~ E from Lucas 7 2~ q(Jl~4[~
Meyer GmbH.
In one ' ' of the invention, a mono-, di- or l-i61y~c~i~1~ of an aliphatic di- or puly~ )v~.ylic acid can be employed as emulsifier to 5 prepare the finely dispersed carotenoid and retinoid . according to the invention. The di- or polyc.~ v~ylic acid may have hydroxyl groups which are l ' ' or substituted by acetyl radicals. Examples of acids which can be used are citric acid or tartaric acid. Examples of acid glycerides which can be used are citric esters of a mono- or o diglyceride (for example Acidan N12~ from Grinstedt), and v;~ ,lyllall.ui~, esters of o~y~,liv~.~ (DATEM, for example Panodan TR0 from Grinstedt).
In one l,.~lbC' of the invention, a sugar fatty acid ester can be 15 employed as emulsifier to prepare the finely dispersed carotenoid and retinoid . ~ according to the invention. It is possible in this case to use plly~;ulvOic~llly tolerated fatty acids such as lauric acid, palmitic acid, stearic acid or mono- or pC,lJ, ' fatty acids such as linoleic acid or linolenic acid. The sugar residue can be any suitable sugar 20 residue, preferably an ascorbyl radical. One example of a sugar fatty acid ester which can be used is ascorbyl palmitate.
It is r j~ C possible to use the emulsifiers as described, for example, in EP-A-0 479 066 or EP-A-0 055 817.
It is r 1~ C possible to use salts of ~Jh~..;vlO6;~.ally tolerated fatty acids as described above, and mono- and v;Oly~,e~idc~ of these fatty acids.
The mono- and di61y-,c.i~ of these fatty acids may, where a be esterifled with fruit acids.
2 1 ) 'i6 ~0 In one r~ of the invention, it is r ih~ lvl~ possible to use i~VI~lY~,Iul esters of these fatty acids.
Lecithin is preferably employed as emulsifier to prepare the finely 5 dispersed carotenoid and retinoid r ' according to the invention.
The emulsifiers which can be used according to the invention, especially lecithin, are 1' ~Divlv~ ally acceptable and can thus be used in .. . ...
It has r~ ,ll..ol~ been found according to the invention that the emulsifiers which can be used according to the invention, especially the lecithin which is used in one i. b~" t, have a very fast ~
action, wilich makes it possible to use them in a high-speed process for i5 preparing finely dispersed carotenoid and retinoid It has been found according to the invention that it is possible to dispense with the use of a protective colloid on use of the emulsifiers according to the invention, especially of lecithin, in the ~ . of 20 finely dispersed carotenoid and retinoid , The omission of a protective colloid leads to liquid carotenoid and retinoid ~ - witb a lower viscosity and a higher content of active ingredient. In addition, especially for yl~ ' ~p~ the number of ingredients in tbe . . is reduced, so that fewer interfering . . ' which may 25 have an effect on the activity of the cDlut~NidD and/or retinoids are present.
The emulsifier used according to the invention, especially tile lecitbin, can in the process according to the mvention be present in the aqueous 30 medium and/or in the organic solvent. rrhus, the emulsifier used accdirlg 2 ~
.9.
to the invention, especially the lecithin, can be present either in the cllcr~nci. prepared before the dissolving, of the carotenoid in the water-miscible organic solvent, or ~ in the water-miscible organic solvent which is at elevated t~ d~ . The emulsifier used according to 5 the invention, especially the lecithin, is preferably added both to the organic carotenoid and retinoid suspension and to the aqueous medium.
The ratio of the amounts of emulsifier used according to the invention,especially lecit~un, to carotenoid or retinoid can be chosen as desired, as o long as f~nely dispersed carotenoid and retinoid . ~ which are stable are obtained.
The ratio of emulsifier used according to the invention, especially of lecithin, to carotenoid or retinoid in the suspension is preferably from 0.1 15 to 5 (ratio of the parts by weight). The ratio is ~ , preferably 0.5 to 2, in particular 0.7 to 1.
It is r '~ ~ possible to change the color of the resulting carotenoid and retinoid . by changing the ratio of amounts of emulsifier 20 used according to the invention, especially lecithin, to carotenoid or retinoid. With high ~)IUpUli- of emulsifier used according to the invention, especially lecithin, for example with a ratio of 2:1 by weight of emulsifier used according to the invention, especially lecithin, to carotene, the resulting products tend to be yellowish, and in the case of 25 carotene and lecithin as emulsifier the latter is at least partially dissolved in the lecithin. With lower ~IU,UUIi- of emulsifler used according to the invention, especially lecithin, relative to carotenoid, such as 0.75:1, for example ~-carotene remains particulate. The color of the suspension is reddish brown in this case.
~ 1 996~
~ o This variability of the color is ~ for use of the carotenoid and retinoid . of the present invention as food dye because it is simple to adapt the color depending on the specific use.
5 r, l1I~IIIUIC, the omission of protective colloids in the carotenoid and retinoid . makes it possible to prepare low-viscosity . .
with high contents of active ingredient, for example of up to 10% by weight based on the finished . . This simplifies the use and the transport of the ~ . because even with high contents of active ingredient they are still able to flow and be metered . ~ rA. ~
For example, this simplifies the use of ~-carotene in the coloring of beverages because liquid metering devices can be used, which generally operate more precisely than solid metering devices in ~ ~
15 plants.
Another advantage of the omission of protective colloids is that the can be used better in 1' ' ~ For example, the . . prepared according to the invention can be used 20 as injection solutions, for example in veterinary medicine.
ANTIOXIDANTS
An antioxidant can be added in the process according to the invention to 25 the water-miscible organic solvent or to the aqueous medium, to the finished suspension of the carotenoid or retinoid and to the ~vt~,~v;J~
and retinoids. The Pntio~ is used to increase the stability of the active ingredient to oxidative breakdown. The ' if used is preferably dissolved together with the ~lut~ id~ or retinoids in the 30 water-miscible organic solvent. Examples of ' ' which can be 2 1 ~640 "
used are ~x-tocopherol, t-~uLylh~lu~y~ulu~, t-bu~ylll~llu~.y,~ vl~ or ethoxyquin. Other suitable ' can also be used.
PREPARATION PROCESS
The carotenoid and retinoid . are prepared according to the invention by dissolving the carotenoid or retinoid in a volatile, water-miscible organic solvent at from 50~C to 250~C, preferably 150 to 200~C, where ~ . under elevated pressure, within less than 10 o sec, and " l~, thereafter mixing the solution with an aqueous medium at from 0 to 90~C, preferably 2-50~C. A procedure of this type is described, for example, in EP-B1-0 065 193. The process described in this patent can be used according to the present invention.
~5 The emulsifler used according to the invention can be present in the aqueous medium and/or in the organic diluent or solvent. The emulsifier, preferably lecithin, is preferably present in the aqueous medium and in the organic diluent or solvent.
20 In one ~ L " of the invention, the emulsifler used according to the invention, preferably lecithin, is added to the water-miscible organic solvent used to prepare the initial suspension of the carotenoid or retinoid, as well as to the aqueous medium, preferably water.
25 If required, the emulsifler used according to the invention can also be present m the heated organic solvent.
Then, in one ~ ~ " of the invention, a suspension of the carotenoid or retinoid in the water-miscible organic solvent is prepared. The water-30 miscible organic solvent used is preferably the same as is used as heated - 12 - 2 ~ 6 4 0 organic solvent in the subsequent step. In one ~ L ' of the invention, the . of the carotenoid or retinoid in this suspension is 2 to 40% by weight, based on the mixture. This suspension or the carotenoid or retinoid is then, in one ~ '~" of the invention, 5 dissolved in heated water-miscible organic solvent within less than 10 sec, preferably less than 5 sec, p~il,ul.~ly preferably less than 2 sec, in particular in fractions of asecond. In this case, heaeed solvent is at from S0 to 200~C, preferably 100 to 180~C, particularly preferably 140 to 180~C. After the time for dissolving the carotenoid or retinoid in the o heated water-miscible organic solvent, the solution is " 'y thereafter mixed with an aqueous medium, at from 0 to 50~C. Water is preferably used as aqueous medium. Mixing the solution with the aqueous medium results in a fine dispersion of the carotenoid or retinoid.
15 The very short time needed to dissolve the carotenoid or retinoid means that the carotenoid or retinoid is exposed to an elevated ~ for only a very short time and is then ~ , cooled again. This makes it possible for the ~ V~lVid~ and/or retinoids to be treated under very mild conditions, and reduces the risk of oxidation or ~' . of the 20 active ingredients. Compared with the process according to the invention, for example, when the active mgredient and solvent are heated together the carotenoid or retinoid is exposed to an elevated t~ tUl~ for a '' "y longer time until it dissolves, and this is associated with tbe risk of oxidation and/or thermal ~-- . of the active ingredient.
In a preferred . b~" of the invention, the process is carried out ' l~, in two mixing chambers. This entails first a suspension of the active ingredient in the organic solvent being prepared and, for example by means of pumps, being fed into a first mixing chamber, into 30 which the heated organic solvent is fed ' '~" so that the active - 2 1 ~ 4 0 ~ 13 -ingredient dissolves in the water-miscible organic solvent in the first mixing chamber at from 50 to 200~C. The active ingredient:
in this first mixing chamber is preferably 0.5 to 10% by weight based on the solution. The volume of the mixing chamber is preferably such that 5 the residence time of the active ingredient suspension and the solvent in the chamber is preferably less than l sec at the chosen delivery rate of the pumps.
The solvent is preferably brought to the required i , ~ by a heat o exchanger before enterjng the mixirlg chamber, while the active ingredient suspension is kept at below 50~C by being fed through a thermally insulated feed line. The mixing in the first mixing chamber is preferably turbulent. After a short residence time, preferably of less than 1 sec, the solution enters a second mixing chamber in which, for exarnple by a 15 pump, water or an aqueous medium is admixed, and the finely dispersed carotenoid and retinoid suspension is p~, 1. The finely dispersed active ingredient suspension can then be discharged from the second mixmg chamber through another line and fed, for example, into a reservoir. To maximize the active mgredient the suspension 20 can be circulated back to the second mixing chamber.
The: of the carotenoid or retinoid in the suspension is in this case preferably 0.1 to 100 g/l.
25 If the pressure exceeds 1 bar, solvents can be used at i . LS above their boiling point (under .' pressure).
In one e ' " of the invention, a product in powder form can be obtained from the resulting . ' for example by the process 30 described in D~A 2 534 091 by spray-drying or spray-cooling or by 21 9~6~0 enveloping the particles, removing and drying in a fluidized bed.
The spray-drying process is described, for example, also in EP-Bl-0 065193.
In one ~ ' " of the invention it is possible to remove, at least partially, the water-miscible organic solvent and/or the aqueous medium from the prepared carotenoid or retinoid . m order to prepare a ' carotenoid or retinoid r ' In this case, the ~o of the carotenoid or retinoid in the suspension can be 0.1 to 100 g/l.
It is possible by adjusting suitable quantity flows to obtain a carotenoid or retinoid suspension with a very small particle size of active ingredient.
15 The particle size in the carotenoid or retinoid suspension is essentially <
1 ~m, preferably in the range from 0.01 to 0.4 ~m, I,.ui ' '~, preferably in the range from 0.03 to 0.2 ~m.
It is possible, for example, to obtain a suspension with an average 20 particle size of active ingredient of 0.03 ~Lm at a carotene of 0.1% by weight based on the finished c~cr~-~;~-- In this case, the suspension has the appearance of a transparent carotene "solution". If the active ingredient content is higher, it is possible in one ~ " of the invention to increase tbe particle size. For example, it can average 25 0.06 ~m in a 0.4% by weight solution. It is possible by the resulting suspension to achieve an active ingredient content of from 1 to 10% by weight based on the finished ~,1 This can take place, for example, by C~l,UUlllliUI~ under mild conditions or by membrane filtration. The resulting . are stable on storage and have a 30 virtually unchanged high specific color strength. The orgaluc solvent 2 1 '7i C,~ 6 ~ ~
employed can, where dlJUIu~J , be removed from the product, depending on the ...~ ,l.,.l;.-~ step used. In a preferred; '-' t, iso-propanol or ethanol is used as solvent, and the carotenoid or retinoid is dissolved at about 180~C in an excess of preheated alcohol so that a 5 ~ 'g. ~ v--- solution is produced.
On mixing with water, which is the aqueous medium preferably used, the alcohol dissolves '~, in the water, resulting in an extremely funely disrersed suspension of the carotenoid or retinoid.
The invention is explained in detail hereinafter by means of an exemplary ;
12.5 g of ,B-carotene are dissolved in 490 g of a solution of 9 g of lecithin (Emulfluid0 E, Lucas Meyer GmbH, prepared by specific partial hydrolysis of natural lecithin, with a l~ .' .' Iiri~' content of 10-15%
by weight, an HLB of 8-9) and 1.8 g of d,l-~-tocopherol in i~v,ulu~
20 (azeotrope) and mixed in a first mixing chamber with 775 g of iav~lu~ vl (azeotrope) which has been heated to 220~C im a heat exchanger. At a metering rate of about 2 l/h for the suspension and 3 I/h for the heated solvent, the residence time in the mixing chamber is 0.35 sec. This results, at 190~C, in a molecular solution which is then 25 fed into a second mixing chamber in which it is subjected to turbulerlt mixing with 7800 g of water (metering rate about 30 l/h). This results in formation of the finely dispersed carotene -r ', which is transferred into a collecting vessel. A clear orange suspension of carotene is obtained in the collecting vessel. The of active ingredient in this case 30 is 0.1% by weight based on ~h fmished . and the specific 21 q9640 color strength (extinction at a path length of 1 cm at the maximum of the absorption band of a yl~ydld~iull diluted to an active ingredient cûntent of S ppm with water) is 0.72. Particle size analysis by photûn cûrrelation ~y~ lu~vyy reveals an average particle size ûf 70 nm.
EXAMrLE 2 120 g of ,i~-carotene are dissolved in 540 g of a sûlution of 43 g of lecithin (Emulfluid~ E, Lucas Meyer GmbH, see Example 1) and 17 g ûf d,l-~Y-tocopherol in isvy~uy~l~ol (azeotrope) and mixed in a first mixing chamber with 825 g of iDVyl~r ' (a2eotrope) which has been heated to 220~C in a heat exchanger. At a metering rate of about 2 I/h for the suspension and 3 I/h for the heated solvent, the residence time in the mixing chamber is 0.35 sec. This results, at 190~C, in a mûlecular sûlution which is then fed into a second mixing chamber in which it is subjected to turbulent mixing with 8800 g of a solution of 43 g of lecithin in 10,400 g of water (metering rate about 30 I/h). This results in formation of the finely dispersed carotene r"spPn~ , which is transferred into a collecting vessel. An orange suspension of carotene is obtained in 20 the collecting vessel. The . of active ingredient in this case is 1% by weight based on the finished . and the specific color strength (extinction at a path length of 1 cm at the maximum of the absorption band of a y.~, diluted to an active ingredient content of S ppm with water) is 0.67. Particle size analysis by photon correlation 25 ~y~,~,Llu~_uy,~ reveals an average particle size of 160 nm.
12.5 g of ,~-carotene are dissolved in 490 g of a solution of 1.8 g of 30 citric ester of a mono/diglyceride (Acidan N12~ from Grinstedt) and 1.8 .
~ ~ - 17--g of d,l-o~-tocopherol in i~v~,.,r ~' (azeotrope) and mixed in a first mixing chamber with 775 g of i~vylu~ ol (azeotrope) which has been heated to 220~C in a heat exchanger. At a metering rate of about 2 I/h for the suspension and 3 I/h for the heated solvent, the residence time in 5 the mixing chamber is 0.35 ~c. This results, at 190~C, in a molecular solution which is then fed into a second mixing chamber in which it is subjected to turbulent mixing with 7800 g of water (metering rate about 30 I/h). This results in formation of the finely dispersed carotene ., which is transferred into a collecting vessel. A clear orange~ suspension of carotene is obtained in the collecting vessel. The of active ingredient in this case is 0.1% by weight based on the finished il ~ and the specific color strength (extinction at a path length of 1 cm at the maximum of the absorption band of a ~lc~ un diluted to an active ingredient content of S ppm witb water) 15 is 0.66. Particle size analysis by photon correlation ~ V~,V~)y reveals an average particle size of 80 nm.
ExA~fpLE 4 20 25 g of ,~-carotene are dissolved in 950 g of a solution of 3.6 g of d;~ ,Lylkul~, ester of l~vllo~ wli~ (Panodan TR~ from Grinstedt) and 3.6 g of d,l-~-tocopherol in isv~, ' (azeotrope) and mixed in a first mixing chamber with 1300 g of i~u~,.,, I (azeotrope) which has been heated to 220~C in a heat exchanger. At a metering rate of about 2 I/h 25 for tne suspension and 3 I/h for the heated solvent, the residence time in the mixing chamber is 0.35 sec. This results, at 190~C, in a molecular solution which is then fed into a second mixing chamber in which it is subjected to turbulent mixing with 15,400 g of water (metering rate about 30 I/h). This results in formation of the finely disper~d carotene 30 , ~, which is transferred into a collecting vessel. A clear orange -18- 2~ ~q~
suspension of carotene is obtained in the collecting vessel The of active ingredient in this case is 0.14% by weight based on the finished . and the specific color strength (extinction at the maximum of the absorption band of a l)ICL~ diluted to an active 5 ingredient content of 5 ppm with water) is 0.72. Particle size analysis by photon correlation ~,IIU:~-,U~ reveals an average particle size of 220 nm.
25 g of ,B-carotene are dissolved in 290 g of a solution of 3.6 g of ascorbyl palmitate and 3.6 g of d,l-~-tocopherol in i~U~ r -' (azeotrope) and mixed in a first mixing chamber with 350 g of isopropanol (azeotrope) which has been heated to 220~C in a heat exchanger. At a 15 metering rate of about 2 I/h for the suspension and 3 I/h for the heated solvent, the residence time in the mixing chamber is 0.35 sec. This results, at 190~C, in a molecular solution which is then fed into a second mixing chamber in which it is subjected to turbulent mixing with 4150 g of water (metering rate about 30 I/h). This results in formatiûn 20 of the finely dispersed carotene , which is transferred into a collecting vessel. A clear orange suspension of carotene is obtained in the collecting vessel. The . of active ingredient in this case is 0.5% by weight based on the finished . ~, and the specific color strength (extinction at the maximum of the absorption band of a 25 ~ diluted to an active ingredient content of S ppm with water) is 0.69. Particle size analysis by photon correlation ~ ,LIU~,U~ reveals an average particle size of 120 nm.
The prepared . ' of ,~-carotene are l'~;.;UIU~ .dlly acceptable and 30 stable on storage for a long time. The ,B-carotene used in the IJI~r ~ -,9- 21 ~43 process is treated under very mild conditions because it is present in the heated solvent for only a very short time (0.35 seconds). The color of the finely dispersed carotenoid suspension varies because of the differences in particle size so that the color can be adjusted and varied depending on 5 the way the process is carried out. The carotenoid ~ r have a high active ingredient content and low viscositv so that dividing into portions is simple, for example in the production of beverages.
Claims (14)
1. A process for preparing finely dispersed carotenoid or retinoid suspensions by dissolving the carotenoid or retinoid in a volatile, water-miscible organic solvent at 50°C-250°C, where appropriate under elevated pressure, within less than 10 sec, and immediately thereafter mixing the solution with an aqueous medium at from 0 to 90°C, wherein the mixing with the aqueous medium takes place in the absence of a protective colloid and in the presence of at least one physiologically tolerated emulsifier.
2. A process as claimed in claim 1, wherein the particle size in the carotenoid or retinoid suspension is essentially less than 1 µm, preferably 0.01-0.4 µm, preferably 0.03-0.2 µm.
3. A process as claimed in claim 1, wherein the water-miscible volatile solvent is at least one alcohol, ketone, ester, acetal or ether or a mixture of one or more thereof, preferably acetone, 1,2-butanediol 1-methyl ether, 1,2-propanediol 1-n-propyl ether, ethanol, n-propanol, isopropanol or a mixture of two or more thereof.
4. A process as claimed in claim 1, wherein lecithin, a fatty acid salt, a mono-, di- or triglyceride, of C12-C18-fatty acids or aliphatic, possibly acetylated, polycarboxylic acids, possibly esterified with fruit acids, a sugar fatty acid ester, or a polyglycerol ester of C12-C18-fatty acids is used as physiologically tolerated emulsifier.
5. A process as claimed in any claims 1 to 4, wherein the carotenoid or retinoid is employed in the dissolving in the form of a suspension in a volatile, water-miscible organic diluent or solvent, preferably in the solvent used in the dissolving.
6. A process as claimed in any of claims 1 to 4, wherein the dissolving of the carotenoid or retinoid in the volatile, water-miscible organic solvent takes place in a mixing chamber, and the mixing of the solution with an aqueous medium takes place in a second mixing chamber which is connected in series with the first mixing chamber, and the process is chosen to be carried out continuously.
7. A process as claimed in any claims 1 to 4, wherein the water-miscible organic solvent and/or the aqueous medium is at least partially removed from the carotenoid or retinoid suspension the carotenoid or retinoid suspension preferably being spray-dried to give a finely dispersed powder.
8. A process as claimed in any of claims 1 to 4, wherein the concentration of the carotenoid or retinoid in the suspension is from 0.1 to 100 g/l.
9. A process as claimed in any of claims 1 to 4, wherein the ratio of emulsifier to carotenoid or retinoid in the suspension is from 0.1 to 5, preferably 0.5 to 2, by weight.
10. A process as claimed in any of claims 1 to 4, wherein the water-miscible organic solvent or, where appropriate, the suspension of the carotenoid or retinoid contains an antioxidant, preferably tocopherol.
11. A carotenoid or retinoid suspension with a particle size of less than 1 µm in a water-containing medium, wherein the suspension contains no protective colloids and contains an emulsifier selected from lecithin, mono-, di- or triglycerides of aliphatic, possibly acetylated, polycarboxylic acids, preferably citric acid or tartaric acid, or ascorbyl palmitate.
12. A suspension as claimed in claim 11, characterized by one or more of the following features:
- the particle size in the carotenoid or retinoid suspension is essentially less than 1 µm, preferably 0.01-0.4 µm, preferably 0.03-0.2 µm;
- lecithin, a fatty acid salt, a mono-, di- or triglyceride of C12-C18-fatty acids or aliphatic, possibly acetylated, polycarboxylic acids, possibly esterified with fruit acids, a sugar fatty acid ester, or a polyglycerol ester of C12-C18-fatty acids is used as physiologically tolerated emulsifier;
- the carotenoid or retinoid in the suspension is from 0.1 to 100 g/l;
- the ratio of emulsifier to carotenoid or retinoid in the suspension is from 0.1 to 5, preferably 0.5 to 2, by weight;
- the water-miscible organic solvent or, where appropriate, the suspension of the carotenoid or retinoid contains an antioxidant, preferably tocopherol.
- the particle size in the carotenoid or retinoid suspension is essentially less than 1 µm, preferably 0.01-0.4 µm, preferably 0.03-0.2 µm;
- lecithin, a fatty acid salt, a mono-, di- or triglyceride of C12-C18-fatty acids or aliphatic, possibly acetylated, polycarboxylic acids, possibly esterified with fruit acids, a sugar fatty acid ester, or a polyglycerol ester of C12-C18-fatty acids is used as physiologically tolerated emulsifier;
- the carotenoid or retinoid in the suspension is from 0.1 to 100 g/l;
- the ratio of emulsifier to carotenoid or retinoid in the suspension is from 0.1 to 5, preferably 0.5 to 2, by weight;
- the water-miscible organic solvent or, where appropriate, the suspension of the carotenoid or retinoid contains an antioxidant, preferably tocopherol.
13. A suspension as claimed in claim 11 or 12, wherein the water-containing medium is a mixture of water and a water-miscible solvent.
14. The use of the carotenoid or retinoid suspension as set forth in claim 1 or of the finely dispersed carotenoid or retinoid powder as set forth in claim 7 as coloring agent for human and animal foods, especially beverages.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19609538.7 | 1996-03-11 | ||
DE19609538A DE19609538A1 (en) | 1996-03-11 | 1996-03-11 | Finely divided carotenoid and retinoid suspensions and process for their preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2199640A1 true CA2199640A1 (en) | 1997-09-11 |
Family
ID=7787960
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002199640A Abandoned CA2199640A1 (en) | 1996-03-11 | 1997-03-10 | Finely dispersed carotenoid and retinoid suspensions and their preparation |
Country Status (10)
Country | Link |
---|---|
US (1) | US5895659A (en) |
EP (1) | EP0795585B1 (en) |
JP (1) | JP3884817B2 (en) |
AT (1) | ATE207515T1 (en) |
AU (1) | AU711746B2 (en) |
BR (1) | BR9701263B1 (en) |
CA (1) | CA2199640A1 (en) |
DE (2) | DE19609538A1 (en) |
ES (1) | ES2166926T3 (en) |
IL (1) | IL120361A (en) |
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DE202007003800U1 (en) * | 2007-03-14 | 2008-07-17 | Sensient Food Colors Germany Gmbh & Co. Kg | Dye emulsion |
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-
1996
- 1996-03-11 DE DE19609538A patent/DE19609538A1/en not_active Withdrawn
-
1997
- 1997-03-03 IL IL12036197A patent/IL120361A/en not_active IP Right Cessation
- 1997-03-07 AU AU16202/97A patent/AU711746B2/en not_active Ceased
- 1997-03-07 AT AT97103860T patent/ATE207515T1/en not_active IP Right Cessation
- 1997-03-07 DE DE59705020T patent/DE59705020D1/en not_active Expired - Lifetime
- 1997-03-07 ES ES97103860T patent/ES2166926T3/en not_active Expired - Lifetime
- 1997-03-07 EP EP97103860A patent/EP0795585B1/en not_active Expired - Lifetime
- 1997-03-10 CA CA002199640A patent/CA2199640A1/en not_active Abandoned
- 1997-03-10 US US08/813,976 patent/US5895659A/en not_active Expired - Lifetime
- 1997-03-11 JP JP05572497A patent/JP3884817B2/en not_active Expired - Fee Related
- 1997-03-11 BR BRPI9701263-7A patent/BR9701263B1/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
ES2166926T3 (en) | 2002-05-01 |
JP3884817B2 (en) | 2007-02-21 |
BR9701263A (en) | 1998-11-10 |
IL120361A0 (en) | 1997-07-13 |
BR9701263B1 (en) | 2009-05-05 |
MX9701750A (en) | 1997-09-30 |
IL120361A (en) | 2001-08-08 |
EP0795585B1 (en) | 2001-10-24 |
DE59705020D1 (en) | 2001-11-29 |
EP0795585A1 (en) | 1997-09-17 |
AU711746B2 (en) | 1999-10-21 |
AU1620297A (en) | 1997-09-18 |
US5895659A (en) | 1999-04-20 |
ATE207515T1 (en) | 2001-11-15 |
JPH101616A (en) | 1998-01-06 |
DE19609538A1 (en) | 1997-09-18 |
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FZDE | Discontinued |