CN108578370B - 叶黄素/叶黄素酯微粒及其制备方法 - Google Patents
叶黄素/叶黄素酯微粒及其制备方法 Download PDFInfo
- Publication number
- CN108578370B CN108578370B CN201810352049.1A CN201810352049A CN108578370B CN 108578370 B CN108578370 B CN 108578370B CN 201810352049 A CN201810352049 A CN 201810352049A CN 108578370 B CN108578370 B CN 108578370B
- Authority
- CN
- China
- Prior art keywords
- lutein
- lutein ester
- ester
- microparticle
- 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.)
- Active
Links
- 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 title claims abstract description 129
- 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 title claims abstract description 72
- 229960005375 lutein Drugs 0.000 title claims abstract description 63
- 239000001656 lutein Substances 0.000 title claims abstract description 60
- 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 title claims abstract description 59
- 235000012680 lutein Nutrition 0.000 title claims abstract description 57
- 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 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000011859 microparticle Substances 0.000 title claims abstract description 20
- KBPHJBAIARWVSC-TWGKZGRNSA-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=CC=C(C)C=C[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-TWGKZGRNSA-N 0.000 title claims description 3
- 239000002245 particle Substances 0.000 claims abstract description 52
- 239000000463 material Substances 0.000 claims abstract description 24
- 229920002472 Starch Polymers 0.000 claims abstract description 20
- 239000008107 starch Substances 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 18
- 238000005507 spraying Methods 0.000 claims abstract description 17
- 239000007957 coemulsifier Substances 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 15
- 239000007908 nanoemulsion Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims description 17
- 239000004373 Pullulan Substances 0.000 claims description 14
- 229920001218 Pullulan Polymers 0.000 claims description 14
- 235000019423 pullulan Nutrition 0.000 claims description 14
- JKQXZKUSFCKOGQ-JLGXGRJMSA-N (3R,3'R)-beta,beta-carotene-3,3'-diol 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=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-JLGXGRJMSA-N 0.000 claims description 13
- JKQXZKUSFCKOGQ-LQFQNGICSA-N Z-zeaxanthin Natural products C([C@H](O)CC=1C)C(C)(C)C=1C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-LQFQNGICSA-N 0.000 claims description 13
- QOPRSMDTRDMBNK-RNUUUQFGSA-N Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCC(O)C1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C QOPRSMDTRDMBNK-RNUUUQFGSA-N 0.000 claims description 13
- 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 claims description 13
- 235000010930 zeaxanthin Nutrition 0.000 claims description 13
- 239000001775 zeaxanthin Substances 0.000 claims description 13
- 229940043269 zeaxanthin Drugs 0.000 claims description 13
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 12
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 12
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 12
- 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 description 9
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 9
- 239000003963 antioxidant agent Substances 0.000 claims description 7
- 230000003078 antioxidant effect Effects 0.000 claims description 7
- 235000006708 antioxidants Nutrition 0.000 claims description 7
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 4
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 4
- QULIOZDJZXKLNY-UHFFFAOYSA-N 3,4,5-trihydroxy-2-propylbenzoic acid Chemical compound CCCC1=C(O)C(O)=C(O)C=C1C(O)=O QULIOZDJZXKLNY-UHFFFAOYSA-N 0.000 claims description 3
- -1 fatty acid ascorbate Chemical class 0.000 claims description 3
- FUWLWBDNQPTINE-UHFFFAOYSA-N 3-tert-butyl-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)C(C(C)(C)C)=CC2=C1 FUWLWBDNQPTINE-UHFFFAOYSA-N 0.000 claims description 2
- 235000005881 Calendula officinalis Nutrition 0.000 claims description 2
- 240000000785 Tagetes erecta Species 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 229930003799 tocopherol Natural products 0.000 claims description 2
- 235000010384 tocopherol Nutrition 0.000 claims description 2
- 239000011732 tocopherol Substances 0.000 claims description 2
- 229960001295 tocopherol Drugs 0.000 claims 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 claims description 2
- 235000008210 xanthophylls Nutrition 0.000 claims 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 1
- 229940072107 ascorbate Drugs 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 239000011668 ascorbic acid Substances 0.000 claims 1
- 239000013078 crystal Substances 0.000 abstract description 15
- 239000008187 granular material Substances 0.000 abstract description 10
- 238000002844 melting Methods 0.000 abstract description 8
- 230000008018 melting Effects 0.000 abstract description 8
- 229920002678 cellulose Polymers 0.000 abstract description 6
- 239000001913 cellulose Substances 0.000 abstract description 6
- 235000013305 food Nutrition 0.000 abstract description 6
- 239000003995 emulsifying agent Substances 0.000 abstract description 5
- 235000013376 functional food Nutrition 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 4
- 230000007547 defect Effects 0.000 abstract description 3
- 238000003860 storage Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 239000000049 pigment Substances 0.000 description 31
- 239000000047 product Substances 0.000 description 28
- 239000000839 emulsion Substances 0.000 description 25
- 230000014759 maintenance of location Effects 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000000084 colloidal system Substances 0.000 description 7
- 238000011049 filling Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000000230 xanthan gum Substances 0.000 description 7
- 229920001285 xanthan gum Polymers 0.000 description 7
- 235000010493 xanthan gum Nutrition 0.000 description 7
- 229940082509 xanthan gum Drugs 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 229960004793 sucrose Drugs 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 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 description 4
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000003094 microcapsule Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- 235000021466 carotenoid Nutrition 0.000 description 3
- 150000001747 carotenoids Chemical class 0.000 description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 3
- 229960003943 hypromellose Drugs 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 235000010378 sodium ascorbate Nutrition 0.000 description 3
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 3
- 229960005055 sodium ascorbate Drugs 0.000 description 3
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- LITUBCVUXPBCGA-WMZHIEFXSA-N Ascorbyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O LITUBCVUXPBCGA-WMZHIEFXSA-N 0.000 description 2
- 239000004261 Ascorbyl stearate Substances 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 235000019276 ascorbyl stearate Nutrition 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000223678 Aureobasidium pullulans Species 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 1
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 244000178231 Rosmarinus officinalis Species 0.000 description 1
- 244000061458 Solanum melongena Species 0.000 description 1
- 235000002597 Solanum melongena Nutrition 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229940107604 lutein esters Drugs 0.000 description 1
- 150000002658 luteins Chemical class 0.000 description 1
- 238000010309 melting process Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 239000007800 oxidant agent Substances 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
- 238000004806 packaging method and process Methods 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000004250 tert-Butylhydroquinone Substances 0.000 description 1
- 235000019281 tert-butylhydroquinone Nutrition 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 125000002640 tocopherol group Chemical group 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
- A23P10/30—Encapsulation of particles, e.g. foodstuff additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
- A23P20/10—Coating with edible coatings, e.g. with oils or fats
- A23P20/15—Apparatus or processes for coating with liquid or semi-liquid products
- A23P20/18—Apparatus or processes for coating with liquid or semi-liquid products by spray-coating, fluidised-bed coating or coating by casting
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
- A61K8/0245—Specific shapes or structures not provided for by any of the groups of A61K8/0241
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Birds (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Emergency Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physics & Mathematics (AREA)
- Geometry (AREA)
- Botany (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Dermatology (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
叶黄素/叶黄素酯微粒及其制备方法，通过将含有叶黄素和/或叶黄素酯、壁材以及助乳化剂的原料混合物在低温条件下制备成粒径不超过1微米的纳米乳液，再喷涂至蔗糖‑淀粉颗粒上制备；所述的壁材是纤维素衍生物。本发明的上述制备方法克服了叶黄素/叶黄素酯原料在制剂化过程中固有的缺陷，避免了高温熔融晶体或溶剂熔融晶体所带来问题；通过纤维素衍生物和助乳化剂的选择与组合，有效解决了叶黄素/叶黄素酯难于乳化的问题。也因此获得有效组分含量高达25％，并具有极其优异的保存稳定性的叶黄素/叶黄素酯微粒产品。该微粒产品可以根据需要应用于制备食品、药品、保健品、功能食品等。
Description
技术领域
本发明涉及一类类胡萝卜素制剂及制备方法。
背景技术
类胡萝卜素因具有较强的抗氧化等功能，市场需求量不断增加。其中万寿菊来源的叶黄素、叶黄素酯和玉米黄质具有独特的眼保护功能，可防止紫外线的损伤。同时可作为强氧化剂抑制活性氧自由基活性，起到护肤保心和增强免疫的作用。我国卫生部公告已经确立批准叶黄素酯、玉米黄质为功能性新资源食品。
目前，叶黄素及其酯和玉米黄质主要应用于眼保护的功能食品、膳食补充剂，以软胶囊和微囊粉的形式为主。近几年来，食用方便的片剂产品不断受到消费者的认可，但压片所使用的原料微囊粉存在机械强度低、稳定性较差的缺点。因此能够应用于打片的具有较高机械强度的叶黄素/叶黄素酯微粒成为压片原料首选。传统制备叶黄素/叶黄素酯微粒的工艺通常选用植物油和叶黄素/叶黄素酯晶体熔融的工艺，将叶黄素/叶黄素酯乳化，再用壁材包埋，该技术在高温熔融时，叶黄素/叶黄素酯含量会大大降低，增加了成本。
例如，CN 201010182547.X中公开的叶黄素酯微粒的制备方法，将叶黄素酯和植物油(大豆油)及抗氧化剂(VE/TBHQ/迷迭香/VC)按照1:2-10:0.01-0.03的比例混合后加热到60-90℃来制备，这种方法不仅会增加油相的载量，造成包埋率低，产品不稳定的缺点，同时高温下的搅拌，也会增加叶黄素酯的降解风险。类似的情况还有CN 201410030538.7、CN201410349554.2和CN 201510511023.3。
叶黄素及叶黄素酯制剂化过程中多使用乳化剂，尽管WO 2016124784A1、WO2016124783A1、WO2016124785A1等在先公开提供了不使用乳化剂的制备方法，分别应用于阿拉伯胶、猪明胶、鱼明胶等保护性壁材体系中。但是不可避免地，这些技术方案中仍然需要将叶黄素及其酯和植物油进行高温熔融后制剂，存在同样问题。
CN 201310117340.8公开了一种纳米叶黄素酯制剂的方法：加热条件下包裹材料(环糊精/羟甲基纤维素钠/羟丙基纤维素钠/聚维酮/聚乙二醇/甘露糖/半乳糖/胆酸)溶于有机溶剂中，叶黄素酯加热溶解在同种有机溶剂(丙酮/甲醇/乙醇/乙酸乙酯)中，在将叶黄素酯乳化，挥干溶剂成型的方法制备叶黄素酯纳米制剂。但是叶黄素酯作为新资源食品，却在制剂化过程中使用有毒的有机溶剂，将大大限制其在食品领域的应用。同样，CN201210458891.6也使用了药用级辅料及有机溶剂大大限制了叶黄素/叶黄素酯的应用。
CN 200610152617.4公开了一种食品级叶黄素水溶性干粉的制备方法：叶黄素与低沸点易挥发的有机溶剂混合，加热溶解后加入水相进行乳化，挥干溶剂进行叶黄素干粉的制备。该方法使用大量毒性有机溶剂，对环境及工作人员造成伤害，并非优选的制备方法。
鉴于以上制备叶黄素/叶黄素酯制剂时的诸多问题，如何在更加温和环保的条件下制备稳定且高质的叶黄素/叶黄素酯微粒制剂，是本申请研究的重点。
发明内容
本发明目的之一在于提供一种含量高、保存稳定的叶黄素/叶黄素酯微粒，通过将含有叶黄素和/或叶黄素酯、壁材以及助乳化剂的原料混合物在低温条件下制备成粒径不超过1微米的纳米乳液，再喷涂至蔗糖-淀粉颗粒上制备；所述的壁材是纤维素衍生物。
相应地，本发明也提供上述叶黄素/叶黄素酯微粒的制备方法，包括下述步骤：
(1)将原料混合物在10-35℃条件下制备成粒径不超过1微米的纳米乳液；
所述的原料混合物含有叶黄素和/或叶黄素酯、壁材以及助乳化剂；
所述的壁材是纤维素衍生物；
(2)将步骤(1)制得的纳米乳液喷涂至蔗糖-淀粉颗粒上。
本发明的上述制备方法克服了叶黄素/叶黄素酯原料在制剂化过程中固有的缺陷，避免了高温熔融晶体或溶剂熔融晶体所带来问题；通过纤维素衍生物和助乳化剂的选择与组合，有效解决了叶黄素/叶黄素酯难于乳化的问题。也因此获得有效组分含量高达25％，并具有极其优异的保存稳定性的叶黄素/叶黄素酯微粒产品。该微粒产品可以根据需要应用于制备食品、药品、保健品、功能食品等。
具体实施方式
本发明提供一种叶黄素/叶黄素酯微粒及其制备方法，所述的方法通过将含有叶黄素和/或叶黄素酯、壁材以及助乳化剂的原料混合物在低温条件下制备成粒径不超过1微米的纳米乳液，再喷涂至蔗糖淀粉颗粒上。
上述技术方案中，所述的低温条件按照本领域通常理解，可限定于10-35℃，优选25-30℃。制备纳米乳液也可以采用现有技术中常用方法，这些方法可举例但不限于胶体磨分散、高压均质的方法。所述的蔗糖淀粉颗粒作为载体，可以根据产品的需求按照现有技术的记载制备。本发明中，使用淀粉与蔗糖按照质量比10：90～30：70的混合物通过制粒机制备的蔗糖淀粉颗粒，粒度要求在150～425微米之间。采用本发明的技术方案可以制得含量为1-25％，并且耐储存的优质叶黄素/叶黄素酯微粒。
进一步具体地描述，上述本发明的叶黄素/叶黄素酯微粒中，所述及的壁材是纤维素衍生物。具体地，所述的壁材是羟丙甲纤维素、甲基纤维素、乙基纤维素、羧甲基纤维素钠中的一种或几种的混合物。最为优选的实施例中的壁材是羟丙甲纤维素。
而该优选技术方案中，壁材限定的技术手段与助乳化剂的搭配选用构建更为优选的技术方案。本发明所述的助乳化剂是黄原胶、普鲁兰多糖或二者的混合物。最优选普鲁兰多糖。黄原胶和普鲁兰多糖均为出芽短梗霉发酵所产生的胞外水溶性粘质多糖，可以商品购得。本发明中所使用的黄原胶是选购自梅花生物科技集团股份有限公司1200-1600厘泊规格，普鲁兰多糖是选购自梅花生物科技集团股份有限公司PLI-10型号，羟丙甲纤维素选自安徽山河药用辅料股份优选公司，SH-E50型号、SH-E15型号、SH-E5型号、SH-E3型号，聚葡糖选自翊圣生物公司15000分子量型号。
进一步优选的技术方案中，所述的壁材与助乳化剂按照特定比例混合。具体实施方式中，壁材和助乳化剂的质量比为5-20:1。优选5-15:1，更优选8-13:1。另一方面，所述的壁材与助乳化剂的用量总和为微粒质量的10-20％。优选13-18％，更优选15-17％。
本发明所述的技术方案中，理论上所有类胡萝卜素类物质都可用于本发明中。优选万寿菊来源的万寿菊来源的叶黄素、玉米黄质、叶黄素酯或其任意混合物。该所述混合物，指前述各组分中任意2中或2中以上的组分，按照任意比例的混合物。
在上述技术方案基础之上，具体的实施方式中，所述的原料混合物中还含有抗氧化剂，所述的抗氧化剂选自生育酚，脂肪酸抗坏血酸酯，丁基羟基甲苯(BHT)，丁基羟基茴香醚(BHA)，丙基没食子酸，叔丁基羟基喹啉或其任意混合物；所述的抗氧化剂质量为微粒质量的0.1-10％；优选1-5％。
再一方面，本发明中队纳米乳液粒径的限定基于必要的试验结果，根据本发明所记载的实施例，粒径控制严格的技术方案中(实施例2和5)，所获得的微粒产物具有显著优异的含量及稳定性。
本发明的叶黄素/叶黄素酯微粒可作为一种原料，进一步加工成片剂、胶囊形式的膳食补充剂，或制成固体饮料、能量棒或糖果形式的食品及功能食品。
下述非限制性实施例用于进一步阐明本发明的技术方案及效果，但不应当理解为对本发明任意形式的限定。
如无特殊说明，本申请中采用下述方法对产品进行测量和评价。
本发明中，采用表面色素含量表征微囊化效率，表面色素含量越高，微囊化效率越低，未包埋的叶黄素/叶黄素酯越多，同时稳定性越差。本发明所述的表面色素含量的测定方法为：5g待测微囊产品加入茄形瓶，向其中加入20ml石油醚(30-60℃)，转摇20s后过滤，重复洗涤两次，合并滤液，旋蒸脱除石油醚，105℃烘干至恒重。剩余固体干重与待测微囊产品的质量比即为表面色素含量，以百分比表示。
本发明所述产品加速稳定性评价方法为中国药典提供的方法：40℃，75％RH条件下，测定的不同时间的色素含量以确定其稳定性优劣。色素保留率为不同时间时产品含量和初始含量的比率。同时提供一种快速评价产品稳定性的方法：60℃，抽真空或充氮气条件下测定20天的稳定性，同样以色素保留率来表示产品稳定性。
本发明所述的乳液粒径由激光粒度仪测定，并记录D99/D90/D50的数值，以μm为单位。
实施例1
在200ml水中加入叶黄素酯晶体170g，抗坏血酸棕榈酸酯20g，抗坏血酸钠30g，维生素E30g，15℃下高速分散1h；常温下将羟丙甲基纤维素100g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的叶黄素酯水溶液中，保持乳液温度为25℃，搅拌30min；经过胶体磨高速分散得到叶黄素酯乳液，乳液粒径为D99/D90/D50＝57.21/47.65/27.52μm，将该乳液以喷涂的形式喷涂在680g、150-200微米的蔗糖-淀粉颗粒表面。叶黄素酯乳液层层包裹后蔗糖-淀粉颗粒后，形成的叶黄素酯微粒A(理论含量为12.2％)，含量12.1％，表面色素含量9.8％，堆密度0.60g/ml。其60℃，真空或充氮条件下，20天的色素保留率77％；其40℃，75％RH条件下的6个月的色素保留率为82％。从该结果可见，未使用助剂的情况下，产品粒径57.21微米，所得产品稳定性差。
实施例2
将普鲁兰多糖16.7g溶于200ml水中，加入叶黄素晶体90g，抗坏血酸棕榈酸酯20g，抗坏血酸硬脂酸酯30g，dl-α-生育酚30g，25℃下高速分散1h；常温下将羟丙甲基纤维素133.3g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的叶黄素水水溶液中，保持乳液温度为25℃，搅拌30min；经过胶体磨高速分散得到叶黄素乳液，乳液粒径为D99/D90/D50＝0.90/0.75/0.21μm，将该乳液以喷涂的形式喷涂在680g、180-300微米的淀粉-糖颗粒表面。叶黄素乳液层层包裹后蔗糖淀粉颗粒后，形成叶黄素微粒B(理论含量为6.3％)，含量6.4％，表面色素含量0.1％，堆密度0.75g/ml。其60℃，真空或充氮条件下，20天的色素保留率98％；其40℃，75％RH条件下的6个月的色素保留率为99.7％。
在本实施例中，添加了普鲁兰多糖作为助乳化剂，羟丙甲基纤维素和普鲁兰多糖总量占颗粒质量的15％，二者的比例为8:1。所得乳液粒径1微米以下，所得叶黄素产品色素保留率高，20天保留率98％。与实施例1相比，可见普鲁兰多糖的添加对粒径和稳定性的影响较大。
实施例3
将葡聚糖8.6g溶于200ml水中，加入玉米黄质晶体170g，BHT 20g，抗坏血酸钠30g，维生素E30g，35℃下高速分散1h；常温下将甲基纤维素172g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的玉米黄质水溶液中，保持乳液温度为30-35℃，搅拌30min；经过胶体磨高速分散得到玉米黄质乳液，乳液粒径为D99/D90/D50＝86.05/57.95/34.23μm，将该乳液以喷涂的形式喷涂在572.8g蔗糖-淀粉颗粒表面。玉米黄质乳液层层包裹后蔗糖-淀粉颗粒后，形成玉米黄质微粒C(理论含量为10.2％)，含量为10.2％，表面色素含量为8.8％，堆密度0.55g/ml。其60℃，真空或充氮条件下，20天的色素保留率80％；其40℃，75％RH条件下的6个月的色素保留率为81％。与实施例2的实验结果对比可见：葡聚糖，甲基纤维素的组合用于本发明所获得的微囊产品，相较实施例2条件下所获得产品在粒径和稳定性两方面都更差一些。
实施例4
将黄原胶12.5g溶于200ml水中，加入玉米黄质晶体35g，叶黄素晶体150g，抗坏血酸棕榈酸酯20g，BHA 30g，维生素E30g，35℃下高速分散1h；常温下将羧甲基纤维素钠187.5g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的玉米黄质质-叶黄素水溶液中，保持乳液温度为30-35℃，搅拌30min；经过胶体磨高速分散得到玉米黄质-叶黄素乳液，乳液粒径为D99/D90/D50＝105.21/87.34/45.38μm，将该乳液以喷涂的形式喷涂在675g、150-250微米的蔗糖-淀粉颗粒表面。玉米黄质-叶黄素乳液层层包裹后蔗糖-淀粉颗粒后，形成玉米黄质-叶黄素微粒D(理论含量为叶黄素10.5％，玉米黄质2.1％)，叶黄素含量为10.4％，玉米黄质含量2.2％，表面色素含量为11.7％，堆密度0.65g/ml。其60℃，真空或充氮条件下，20天的色素保留率74％；其40℃，75％RH条件下的6个月的色素保留率为76％。与实施例2的实验结果对比可见：黄原胶和羧甲基纤维素钠的组合用于本发明所获得的微囊产品，相较实施例2条件下所获得产品在粒径和稳定性两方面都更差一些。
实施例5
将普鲁兰多糖121.4g溶于200ml水中，加入叶黄素酯晶体3570g，35℃下高速分散1h；常温下将羟丙甲纤维素1578.2g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的叶黄素酯水溶液中，保持乳液温度为30℃，搅拌30min；经过胶体磨高速分散得到叶黄素酯乳液，乳液粒径为D99/D90/D50＝0.92/0.47/0.23μm，将该乳液以喷涂的形式喷涂在4730.4g、300-425微米的蔗糖-淀粉颗粒表面。叶黄素酯乳液层层包裹后蔗糖-淀粉颗粒后，分别于喷涂12h、20h、24h时取样，得到叶黄素酯产品E、F、G(理论含量分别为12.1％、21.0％、25.0)。含量分别为11.9％、20.2％、25.1％，表面色素含量分别为0.25％、0.27％、0.31％，堆密度分别为0.75g/ml、0.78g/ml、0.77g/ml。其60℃，真空或充氮条件下，20天的色素保留率分别为99.8％、100.2％、99.3％；其40℃，75％RH条件下的6个月的色素保留率为98.2％、99.6％、97.5％。
实施例6
将黄原胶21.7g溶于200ml水中，加入叶黄素酯晶体170g，抗坏血酸硬脂酸酯20g，抗坏血酸钠30g，维生素E30g，25℃下高速分散1h；常温下将羟丙甲纤维素108.5g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的叶黄素酯水溶液中，保持乳液温度为35℃，搅拌30min；经过胶体磨高速分散得到叶黄素酯乳液，乳液粒径为D99/D90/D50＝65.21/34.34/23.38μm，将该乳液以喷涂的形式喷涂在150-425微米的619.8g蔗糖-淀粉颗粒表面。叶黄素酯乳液层层包裹后蔗糖-淀粉颗粒后，形成叶黄素酯微粒H(理论含量为叶黄素酯12.2％)，叶黄素酯含量为12.4％，表面色素含量为9.7％，堆密度0.55g/ml。其60℃，真空或充氮条件下，20天的色素保留率82％；其40℃，75％RH条件下的6个月的色素保留率为79％。
实施例7
将100g叶黄素酯晶体溶于300g橄榄油中，加热至60-90℃溶解晶体，晶体熔融后加入到520g阿拉伯胶水溶液中，搅拌分散后，加入抗坏血酸棕榈酸酯20g，丙基没食子酸30g，维生素E30g，以喷雾干燥工艺制备叶黄素酯微粒，得到叶黄素酯微粒I，含量为6.5％(理论含量8.0％)，表面色素含量为7.7％，堆密度0.35g/ml。其60℃，真空或充氮条件下，20天的色素保留率50％；其40℃，75％RH条件下的6个月的色素保留率为56％。
本实施例的处理方法代表了本领域现有技术中处理的一般方法，即采用加热熔融的方法处理物料。与实施例2的技术方案及效果相比可见：加热熔融过程中活性物质含量就有损失，同时得到产品后产品稳定性也很差，与本发明的方案存在实质差异。
实施例8：叶黄素/叶黄素酯产品打片稳定性
将实施例1-6中的叶黄素/叶黄素酯微粒，和多种维生素打片辅料混料后，添加量为10mg/片，使用天峰ZPW-8型旋转式压片机进行压片，得到复合类叶黄素/叶黄素酯维生素片，片剂硬度80-100N，脆碎度≤0.1％，将片剂包装在其盖用热封铝箔密封的HDPE瓶中，在40℃和75％的相对湿度下将片剂储存6个月，不同时间色素含量保留率见表1。
从表1的数据可以看出以普鲁兰多糖和羟丙甲纤维素组合使用的微粒B和G在产品应用方面具有较好特性，产品稳定性高。其他形式的产品稳定性较B和G差。
表1
Claims (6)
1.叶黄素/叶黄素酯微粒，通过将含有叶黄素和/或叶黄素酯、壁材以及助乳化剂的原料混合物在10-35℃条件下制备成粒径不超过1微米的纳米乳液，再喷涂至蔗糖-淀粉颗粒上制备；所述的壁材是羟丙甲纤维素；所述的助乳化剂为普鲁兰多糖。
2.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的壁材和助乳化剂的质量比为5-20:1。
3.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的壁材与助乳化剂的用量总和为微粒质量的10-20%。
4.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的叶黄素/叶黄素酯为万寿菊来源的叶黄素、玉米黄质、叶黄素酯或其任意混合物。
5.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的原料混合物中还含有抗氧化剂，所述的抗氧化剂选自生育酚，脂肪酸抗坏血酸酯，丁基羟基甲苯，丁基羟基茴香醚，丙基没食子酸，叔丁基羟基喹啉或其任意混合物；所述的抗氧化剂质量为微粒质量的0.1-10%。
6.权利要求1所述的叶黄素/叶黄素酯微粒的制备方法，包括下述步骤：(1) 将原料混合物在10-35℃条件下制备成粒径不超过1微米的纳米乳液；所述的原料混合物含有叶黄素和/或叶黄素酯、壁材以及助乳化剂；所述的壁材是羟丙甲纤维素；所述的助乳化剂为普鲁兰多糖；(2) 将步骤(1)制得的纳米乳液喷涂至蔗糖-淀粉颗粒上。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810352049.1A CN108578370B (zh) | 2018-04-19 | 2018-04-19 | 叶黄素/叶黄素酯微粒及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810352049.1A CN108578370B (zh) | 2018-04-19 | 2018-04-19 | 叶黄素/叶黄素酯微粒及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108578370A CN108578370A (zh) | 2018-09-28 |
| CN108578370B true CN108578370B (zh) | 2021-01-19 |
Family
ID=63613696
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810352049.1A Active CN108578370B (zh) | 2018-04-19 | 2018-04-19 | 叶黄素/叶黄素酯微粒及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108578370B (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2024509226A (ja) * | 2021-12-28 | 2024-02-29 | 大▲連▼医▲諾▼生物股▲ふん▼有限公司 | カロテノイド製剤、調製方法、及びその応用 |
| CN114504104A (zh) * | 2022-01-23 | 2022-05-17 | 大连医诺生物股份有限公司 | 一种掩味速溶叶黄素酯产品、其制备方法及应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102389108A (zh) * | 2011-10-10 | 2012-03-28 | 大连医诺生物有限公司 | 叶黄素酯微囊粉及其制备方法 |
| CN103330213A (zh) * | 2013-05-10 | 2013-10-02 | 杭州普丽美地生物科技有限公司 | 一种茶多酚脂溶性微胶囊及其制备方法 |
| CN103406079A (zh) * | 2013-06-28 | 2013-11-27 | 大连医诺生物有限公司 | 不使用有机溶剂制备冷水分散型类胡萝卜素微囊粉的方法 |
| CN107712900A (zh) * | 2017-10-24 | 2018-02-23 | 宝得瑞（湖北）健康产业有限公司 | 一种功能性中长链脂肪酸甘油酯微胶囊及其生产方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11278856B2 (en) * | 2015-01-28 | 2022-03-22 | Chenguang Biotech Group Co., Ltd | Lutein microcapsule formulation and preparation method thereof |
-
2018
- 2018-04-19 CN CN201810352049.1A patent/CN108578370B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102389108A (zh) * | 2011-10-10 | 2012-03-28 | 大连医诺生物有限公司 | 叶黄素酯微囊粉及其制备方法 |
| CN103330213A (zh) * | 2013-05-10 | 2013-10-02 | 杭州普丽美地生物科技有限公司 | 一种茶多酚脂溶性微胶囊及其制备方法 |
| CN103406079A (zh) * | 2013-06-28 | 2013-11-27 | 大连医诺生物有限公司 | 不使用有机溶剂制备冷水分散型类胡萝卜素微囊粉的方法 |
| CN107712900A (zh) * | 2017-10-24 | 2018-02-23 | 宝得瑞（湖北）健康产业有限公司 | 一种功能性中长链脂肪酸甘油酯微胶囊及其生产方法 |
Non-Patent Citations (1)
| Title |
|---|
| 叶黄素酯微囊粒的制备工艺优化;徐建中等;《食品科技》;20171231;第42卷(第6期);第240-246页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108578370A (zh) | 2018-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11278856B2 (en) | Lutein microcapsule formulation and preparation method thereof | |
| Hu et al. | Preparation, characterization, and in vitro release investigation of lutein/zein nanoparticles via solution enhanced dispersion by supercritical fluids | |
| JP5377365B2 (ja) | 疎水性栄養素の安定なビーズ | |
| AU2017203887B2 (en) | Improved pharmaceutical compositions of pimobendan | |
| EP1300394B1 (en) | Method for the production of a water-dispersible formulation containing carotenoids | |
| CN108578370B (zh) | 叶黄素/叶黄素酯微粒及其制备方法 | |
| EP3253233B1 (en) | Microcapsules comprising lutein or lutein ester | |
| CN109317066B (zh) | 一种肉豆蔻精油微胶囊及其制备方法和应用 | |
| CA2926424C (en) | Aprepitant oral liquid formulations | |
| CN108185424A (zh) | 类胡萝卜素微粒制剂及其制备方法 | |
| US20150209400A1 (en) | Composition of oily, pungent and odoriferous substances and a process of preparation thereof | |
| CN101016259A (zh) | 一种高全反式β－胡萝卜素制剂的制备方法 | |
| CN112891310A (zh) | 一种大麻二酚粉末的制备方法、制备得到的大麻二酚粉末及其用途 | |
| EP2933290B1 (en) | Composition for forming complex, complex formed therefrom, and composition for oral administration including said complex | |
| US9399020B2 (en) | Hydrophilic matrix beadlet compositions with enhanced bioavailability | |
| JP6211220B1 (ja) | カプセル用アントシアニン含有組成物及びカプセル剤 | |
| WO2007014566A2 (en) | Microcapsules and their use | |
| Luján-Medina et al. | Microencapsulation of ellagic acid from pomegranate husk and karaya gum by spray drying | |
| JPWO2014017507A1 (ja) | 固形製剤 | |
| CA2793783C (en) | Novel coating system | |
| CN110898015A (zh) | 一种伊曲康唑制剂的制备方法 | |
| JP6715645B2 (ja) | ルテインを高含有する粉末状組成物及び製造方法 | |
| JP2007135516A (ja) | プロポリス粉体被覆物及びその製造方法、並びにプロポリス含有食品 | |
| CN105560603A (zh) | 一种新型茶多酚球形颗粒 | |
| CN117337978A (zh) | 一种用于压片制剂的叶黄素或其衍生物颗粒及其制备方法和应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |