CN114287625B - Carotenoid preparation and application thereof - Google Patents
Carotenoid preparation and application thereof Download PDFInfo
- Publication number
- CN114287625B CN114287625B CN202111682238.3A CN202111682238A CN114287625B CN 114287625 B CN114287625 B CN 114287625B CN 202111682238 A CN202111682238 A CN 202111682238A CN 114287625 B CN114287625 B CN 114287625B
- Authority
- CN
- China
- Prior art keywords
- carotenoid
- preparation
- stirring
- pretreated
- wall material
- 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
- 235000021466 carotenoid Nutrition 0.000 title claims abstract description 55
- 150000001747 carotenoids Chemical class 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 239000013078 crystal Substances 0.000 claims abstract description 44
- 238000003756 stirring Methods 0.000 claims abstract description 37
- 239000000463 material Substances 0.000 claims abstract description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000000049 pigment Substances 0.000 claims abstract description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000002156 mixing Methods 0.000 claims abstract description 18
- 238000004090 dissolution Methods 0.000 claims abstract description 17
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 12
- 235000013361 beverage Nutrition 0.000 claims abstract description 9
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 8
- 238000010008 shearing Methods 0.000 claims abstract description 8
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 6
- 239000000843 powder Substances 0.000 claims abstract description 5
- 235000013305 food Nutrition 0.000 claims abstract description 4
- 239000006185 dispersion Substances 0.000 claims abstract description 3
- 239000008187 granular material Substances 0.000 claims abstract description 3
- 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 claims description 40
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 31
- 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 29
- 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 claims description 24
- 239000000243 solution Substances 0.000 claims description 23
- -1 sucrose fatty acid ester Chemical class 0.000 claims description 23
- 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 21
- 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 21
- 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 21
- 239000001775 zeaxanthin Substances 0.000 claims description 21
- 235000010930 zeaxanthin Nutrition 0.000 claims description 21
- 229940043269 zeaxanthin Drugs 0.000 claims description 21
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 20
- 239000000194 fatty acid Substances 0.000 claims description 20
- 229930195729 fatty acid Natural products 0.000 claims description 20
- 239000001656 lutein Substances 0.000 claims description 19
- 235000012680 lutein Nutrition 0.000 claims description 19
- 229960005375 lutein Drugs 0.000 claims description 19
- 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 claims description 19
- 239000007787 solid Substances 0.000 claims description 19
- 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 claims description 19
- 229930006000 Sucrose Natural products 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 17
- 239000005720 sucrose Substances 0.000 claims description 17
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 15
- 235000010323 ascorbic acid Nutrition 0.000 claims description 15
- 239000011668 ascorbic acid Substances 0.000 claims description 15
- 239000008103 glucose Substances 0.000 claims description 15
- 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 14
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims description 14
- 229960005070 ascorbic acid Drugs 0.000 claims description 14
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims description 14
- 239000011648 beta-carotene Substances 0.000 claims description 14
- 235000013734 beta-carotene Nutrition 0.000 claims description 14
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims description 14
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims description 13
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims description 13
- 229960002747 betacarotene Drugs 0.000 claims description 13
- 239000006188 syrup Substances 0.000 claims description 10
- 235000020357 syrup Nutrition 0.000 claims description 10
- GUOCOOQWZHQBJI-UHFFFAOYSA-N 4-oct-7-enoxy-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)OCCCCCCC=C GUOCOOQWZHQBJI-UHFFFAOYSA-N 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 235000009508 confectionery Nutrition 0.000 claims description 9
- 229940080313 sodium starch Drugs 0.000 claims description 9
- 235000006708 antioxidants Nutrition 0.000 claims description 7
- 150000001720 carbohydrates Chemical class 0.000 claims description 7
- 235000014633 carbohydrates Nutrition 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 7
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims description 4
- ANVAOWXLWRTKGA-XHGAXZNDSA-N all-trans-alpha-carotene Chemical compound CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1C(C)=CCCC1(C)C ANVAOWXLWRTKGA-XHGAXZNDSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 4
- 239000012530 fluid Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 claims description 3
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 claims description 2
- 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 claims description 2
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 claims description 2
- 240000008042 Zea mays Species 0.000 claims description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 2
- 239000011795 alpha-carotene Substances 0.000 claims description 2
- 235000003903 alpha-carotene Nutrition 0.000 claims description 2
- ANVAOWXLWRTKGA-HLLMEWEMSA-N alpha-carotene Natural products C(=C\C=C\C=C(/C=C/C=C(\C=C\C=1C(C)(C)CCCC=1C)/C)\C)(\C=C\C=C(/C=C/[C@H]1C(C)=CCCC1(C)C)\C)/C ANVAOWXLWRTKGA-HLLMEWEMSA-N 0.000 claims description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims description 2
- 239000001168 astaxanthin Substances 0.000 claims description 2
- 235000013793 astaxanthin Nutrition 0.000 claims description 2
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 claims description 2
- 229940022405 astaxanthin Drugs 0.000 claims description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 2
- 235000005822 corn Nutrition 0.000 claims description 2
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 claims description 2
- 229940107187 fructooligosaccharide Drugs 0.000 claims description 2
- 230000002496 gastric effect Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000001751 lycopene Substances 0.000 claims description 2
- 235000012661 lycopene Nutrition 0.000 claims description 2
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 claims description 2
- 229960004999 lycopene Drugs 0.000 claims description 2
- 235000015097 nutrients Nutrition 0.000 claims description 2
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 claims description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 125000000185 sucrose group Chemical group 0.000 claims 1
- 230000000007 visual effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 26
- 238000001879 gelation Methods 0.000 abstract description 4
- 230000004071 biological effect Effects 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000005469 granulation Methods 0.000 abstract description 2
- 230000003179 granulation Effects 0.000 abstract description 2
- 238000004945 emulsification Methods 0.000 abstract 1
- 238000012423 maintenance Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 41
- 230000000694 effects Effects 0.000 description 12
- 108010010803 Gelatin Proteins 0.000 description 9
- 239000008273 gelatin Substances 0.000 description 9
- 229920000159 gelatin Polymers 0.000 description 9
- 235000019322 gelatine Nutrition 0.000 description 9
- 235000011852 gelatine desserts Nutrition 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 238000001694 spray drying Methods 0.000 description 8
- 230000001804 emulsifying effect Effects 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 244000000626 Daucus carota Species 0.000 description 4
- 235000002767 Daucus carota Nutrition 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- JKQXZKUSFCKOGQ-YOPUJPICSA-N meso-zeaxanthin Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C[C@H](O)CC1(C)C JKQXZKUSFCKOGQ-YOPUJPICSA-N 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- JKQXZKUSFCKOGQ-QAYBQHTQSA-N zeaxanthin Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-QAYBQHTQSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 238000004040 coloring Methods 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- 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 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920002774 Maltodextrin Polymers 0.000 description 2
- 239000005913 Maltodextrin Substances 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 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 2
- 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 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 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 description 2
- FDSDTBUPSURDBL-LOFNIBRQSA-N canthaxanthin Chemical compound CC=1C(=O)CCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)CCC1(C)C FDSDTBUPSURDBL-LOFNIBRQSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229940035034 maltodextrin Drugs 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 239000004267 EU approved acidity regulator Substances 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- 102000009127 Glutaminase Human genes 0.000 description 1
- 108010073324 Glutaminase Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- OOUTWVMJGMVRQF-DOYZGLONSA-N Phoenicoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)C(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)C(=O)CCC2(C)C OOUTWVMJGMVRQF-DOYZGLONSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001659 canthaxanthin Substances 0.000 description 1
- 235000012682 canthaxanthin Nutrition 0.000 description 1
- 229940008033 canthaxanthin Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 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 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 229940095686 granule product Drugs 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229960001708 magnesium carbonate Drugs 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 150000002772 monosaccharides Chemical group 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 235000013826 starch sodium octenyl succinate Nutrition 0.000 description 1
- 239000001334 starch sodium octenyl succinate Substances 0.000 description 1
- 230000000365 steroidogenetic effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 150000003505 terpenes Chemical group 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a carotenoid preparation and application thereof, wherein the preparation is prepared by mixing pretreated carotenoid and pretreated gelation wall material, and carrying out emulsification treatment and granulation to obtain powder or granule products; wherein the preparation method of the pretreated carotenoid comprises the following steps: mixing carotenoid with 3-5 times of 50-70% ethanol water solution, stirring at 40-50deg.C for at least 20min, high-speed shearing for dispersion, adding antioxidant, removing solvent at 70-80deg.C until ethanol residue is less than 10ppm, and simultaneously water content of crystal is 10-30%. The product produced by the method can not only reduce pigment dissolution, but also slow release, stability and effective maintenance of biological activity. Can be widely applied in the fields of food, beverage, health care products, medicines and the like.
Description
Technical Field
The invention relates to the technical field of microparticle preparation, in particular to a carotenoid preparation and application thereof.
Background
Carotenoids (carotenoids) are a class of polyenes that are yellow, orange-red or red, generally composed of 8 isoprenoid units, and have the formula C 40 H 56 . Carotenoids, which are well known to have beneficial effects on physical health, are physiological antioxidants that block lipid peroxidation and thereby protect the follicular and uterine steroidogenic cells from oxidation. The carotenoid is provitamin A, and has effects in preventing night blindness, resisting oxidation, preventing cancer, and enhancing tinting strength. However, carotenoids are insoluble in water, but have low solubility in fats and oils, and are unstable to light, oxygen, and heat, limiting their use. Conventional methods increase the bioavailability and also the coloring power of carotenoids by microencapsulating them to form an encapsulated product, e.g., some beautiful cakes, beverages, all of which are derived from carotenoids.
At the same time, the improvement of the coloring ability brings about troubles such as the product being easily dyed on hands, clothes and even on the face, and the tongue surface and the cup are dyed after the carotenoid product is taken, thereby bringing about a bad experience to people. None of the methods can maintain the biological activity of carotenoid, reduce the dyeing ability, etc., and is better used by people, which is a problem that researchers in the field think all the time. A common solution to this problem is to crosslink gelatin or protein to give crosslinked beads.
For example, patent GB993138 discloses a method for stabilizing gelatin-containing vitamin products, wherein formaldehyde, glutaraldehyde or the like is used as a crosslinking agent, and heat treatment is performed.
Patent CN1283454a provides a method for preparing small beads of fat-soluble material, using radiation or glutaminase for cross-linking of gelatin, followed by spray drying into a starch powder.
Patent CN1764439a provides a method for preparing crosslinked bright beads, crosslinked for 30 seconds to 30 minutes using 90-140 ℃.
The main problem with these patents is that crosslinking is carried out using high temperatures and for too long a time, thereby destroying the labile fat-soluble components or carotenoids.
Patent CN1303670A provides a powdery stable vitamin and/or carotenoid product and a preparation method thereof, and uses alkali metal phosphate cross-linking agent to cross-link protein materials such as gelatin, casein and the like, so as to achieve the effect of insolubility in water at 100 ℃ for 3 min. Although it is claimed to reduce the temperature of thermal crosslinking, the condition of heating temperature of 55 to 180 ℃ is still used in the actual production process.
The above patent solves or partially solves the problem of carotenoid dissolution in water, but uses gelatin and protein, and the obvious gelatin and protein can partially achieve the purpose of reducing pigment dissolution after crosslinking. However, the prior art does not teach how to use other types of wall materials to prepare products of non-staining carotenoid formulations.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a carotenoid preparation prepared by using non-gelatin and protein raw materials as wall materials and application thereof, which can effectively reduce the coloring capability of carotenoid and still maintain the bioactivity of carotenoid application.
The invention provides a carotenoid preparation, which is prepared by mixing pretreated carotenoid and pretreated gelation wall material, emulsifying and granulating to obtain powder or granule product;
wherein the preparation method of the pretreated carotenoid comprises the following steps: mixing carotenoid with 3-5 times of 50-70% ethanol water solution, stirring at 40-50deg.C for at least 20min, high-speed shearing for dispersion, adding antioxidant, removing solvent at 70-80deg.C until ethanol residue is less than 10ppm, and simultaneously water content of crystal is 10-30%.
For the technical solutions described above, it is preferred that said carotenoid is selected from lutein and fatty acid esters thereof, zeaxanthin, lycopene, alpha-carotene, beta-carotene, canthaxanthin, astaxanthin or mixtures thereof.
The above-mentioned components and their mixture are mixed according to any ratio.
For the technical scheme, preferably, the total pigment content of the carotenoid is more than 80% after pretreatment; more preferably from lutein or fatty acid esters thereof, zeaxanthin, beta-carotene or mixtures thereof; most preferred is a mixture of lutein or its fatty acid esters, zeaxanthin and beta-carotene mixed in the weight ratio of (1-3): 1-3.
For the above described technical scheme, it is preferred that the zeaxanthin contains two isomers, namely (3R, 3 'R) -zeaxanthin and (3R, 3' S) -zeaxanthin; wherein the ratio of (3R, 3 'R) -zeaxanthin to (3R, 3' S) -zeaxanthin is 5% -15%:95% -85%.
For the above technical solution, preferably, the preparation method of the pretreated gelled wall material is: mixing the wall material and the carbohydrate according to the weight ratio of 1-5:1, preparing an aqueous solution with the solid content of 50-70%, stirring and dispersing at 50-70 ℃, stirring at 80-90 ℃ for 35-50min, cooling to 60-65 ℃ and treating for 100-150min, preferably 110-130min.
For the technical scheme, preferably, the weight ratio of the wall material to the carbohydrate is 1-3:1; the most preferred weight ratio is 3:1.
For the above technical solution, preferably, the wall material is at least one selected from sodium starch octenyl succinate, acacia and cellulose derivatives; most preferred is sodium starch octenyl succinate.
For the above described embodiments, preferably, the carbohydrate is selected from monosaccharides of not more than 10 carbons joined by glycosidic linkages to form a straight or branched chain sugar, such as, but not limited to, sucrose, glucose syrup, xylose, isomaltooligosaccharide, fructooligosaccharide, solid corn syrup or mixtures thereof. Among them, glucose syrup having a solid content of 50 to 90% and sucrose or a mixture thereof in an arbitrary ratio are preferable.
For the technical solutions described above, it is preferred that the granulation process comprises spray drying, fluid drying, etc. to obtain a powder or granulate product.
For the technical solutions described above, it is preferred that the amount of gelled wall material is calculated on the basis of the final product mass of the carotenoid preparation and is 40-70%, preferably 50-70% of the final product mass.
For the technical solutions described above, preferably, the antioxidant is selected from ascorbic acid, ascorbyl palmitate, sucrose fatty acid ester, tocopherol, fatty acid ascorbate, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), propyl gallate, tert-butylhydroxyquinoline or mixtures thereof; more preferably: ascorbic acid, ascorbyl palmitate and sucrose fatty acid ester in the weight ratio of 2-5:0.1-3: 0.1-3.
For the technical solutions described above, it is preferred that the antioxidant is used in an amount of 5-30% by weight of the carotenoid. More preferably 18-28%.
For the technical scheme, preferably, the carotenoid preparation has pigment dissolution rate of less than 5% in water.
For the technical scheme, preferably, the carotenoid preparation has a certain slow release effect, and the release speed in gastrointestinal fluid is 0.5h < 35%, and 4h > 90%.
The second aspect of the invention provides the application of the non-staining carotenoid preparation, including the application in the fields of food, beverage, health care products, medicines and the like; especially soft sweets, solid beverages and liquid beverages, and can be applied to eye gel and eye drops.
Compared with the prior art, the invention has the following beneficial effects:
1. after the treatment by the method provided by the invention, the product has the characteristic of reducing pigment dissolution, and is especially suitable for being applied to products requiring nutrient visualization effect.
2. After the treatment by the method provided by the invention, the product has the characteristic of slow release, and the product is better stored in the stomach from the other aspect, so that the acid resistance is realized.
3. After the carotenoid is pretreated, the stability is improved, and the biological activity of the carotenoid application can be still maintained.
4. The organic solvent is not used in the operation process, and the preparation process is environment-friendly.
5. The non-gelatin and protein raw materials are used as wall materials, so that the method for preparing the non-staining carotenoid preparation is enriched.
Drawings
FIG. 1 shows that the products prepared by the methods of example 2 and comparative example 4 of the present invention are applied to soft candy, a is the transparent appearance of the carotenoid prepared by the method of the present invention without impregnating the soft candy, B is the beta-carotene product B prepared by the method of comparative example 4, the soft candy is dyed red, and the transparency of the soft candy is reduced.
Detailed Description
The present invention will be further described with reference to examples, but it should be understood that the scope of the present invention is not limited by the examples.
In the present invention, percentages and percentages are by mass unless explicitly stated otherwise. Unless otherwise specified, all experimental procedures used are conventional and all materials, reagents, etc. used are commercially available.
The non-staining carotenoid preparation of the invention can also be selectively added with one or more of the following components according to the conventional dosage in the field:
(1) Water-soluble ingredients such as, but not limited to, glucose, lactose, isomaltooligosaccharide, polyethylene glycol, sodium carboxymethyl cellulose, solid glucose syrup.
(2) Surfactants are used to solve the problem that products made of water insoluble fats or waxy materials typically float on the water surface, increasing the water dispersibility of the product. The surfactant may be, for example, but not limited to, tween 60, tween 80 or sucrose fatty acid ester.
(3) Examples of binders include, but are not limited to, povidone, glycerol, propylene glycol, polyglycerin fatty acid esters, soluble soybean polysaccharides, and sodium carboxymethyl cellulose.
(4) Suspending agents such as, but not limited to, guar gum, xanthan gum, sodium alginate, hydroxypropyl methylcellulose, gellan gum, carrageenan.
(5) Diluents such as, but not limited to, starch, maltodextrin, dibasic calcium phosphate.
(6) Stabilizers, such as but not limited to sodium lactate, sodium citrate, magnesium carbonate, sodium bicarbonate, microcrystalline cellulose.
(7) Glidants such as, but not limited to, silicon dioxide, corn starch, calcium silicate.
(8) Antioxidants, such as but not limited to vitamin E, vitamin C and derivatives thereof.
(9) Acidity regulators, such as but not limited to citric acid, lactic acid, malic acid.
The following method is adopted to measure and evaluate the product.
The method for measuring the pigment dissolution rate comprises the following steps: 1g of the product is taken, 50mL of water is added, the temperature is 90 ℃, the rotating speed is 100, stirring and dissolution are carried out for 30min, then the mixture is filtered and transferred into a volumetric flask, 30mL of water is used for washing once, the filtrates are combined, and the OD value of the maximum absorption wavelength is measured after the volume is fixed. Pigment dissolution was (OD value/product mass) ×100%.
The method for evaluating the acceleration stability of the product is a method provided by Chinese pharmacopoeia: the pigment content was measured at 40℃and 75% RH for various times to determine the stability, and the pigment retention was used to represent the stability of the product. Pigment retention is the ratio of product content to initial content at various times, expressed as a percentage.
The release assay according to the present invention was carried out in accordance with DELAYED-RELEASE DOSAGE FORMS method B, with reference to USP < 711 > DISOLUTIO, using Apparatus 2 at a rotation speed of 50rpm, wherein a 0.1N hydrochloric acid solution was selected as a release medium within two hours and a phosphate buffer having a pH of 6.8 was selected as a release medium within 2 to 8 hours.
Example 1 Effect of Crystal treatment on Crystal stability
(1) 160g of zeaxanthin crystals and 4 times of 60% ethanol water solution are mixed, stirred for 30min at 45 ℃, sheared and dispersed at 10000 revolutions at high speed, 28g of ascorbic acid, 10g of ascorbyl palmitate, 10g of sucrose fatty acid ester are added, the solvent is removed at 75 ℃, the ethanol residue is 8ppm, and the water content of the crystals is 12.3%, thus obtaining zeaxanthin crystals A.
(2) 160g of zeaxanthin crystals and 4 times of 60% ethanol water solution are mixed, stirred for 30min at 45 ℃, sheared and dispersed at 10000 revolutions at high speed, 28g of ascorbic acid and 10g of ascorbyl palmitate are added, the solvent is removed at 75 ℃, the ethanol residue is 55ppm, and the water content of the crystals is 25%, thus obtaining zeaxanthin crystals B.
(3) 160g of zeaxanthin crystals and 8 times of 80% ethanol water solution are mixed, stirred for 30min at 45 ℃, sheared and dispersed at 10000 revolutions at high speed, 28g of ascorbic acid, 10g of ascorbyl palmitate, 10g of sucrose fatty acid ester are added, the solvent is removed at 75 ℃, 155ppm of ethanol residues is dissolved, and the water content of the crystals is 32%, so that zeaxanthin crystals C are obtained.
(4) 160g of zeaxanthin crystals, 28g of ascorbic acid, 10g of ascorbyl palmitate, 10g of sucrose fatty acid ester were mixed to obtain zeaxanthin crystals D.
(5) The above zeaxanthin crystals A to D were heated at 60℃to measure pigment retention at various times, and the results were shown in Table 1 below:
TABLE 1 pigment retention at various times
A | B | C | D | |
0 | 100% | 100% | 100% | 100% |
1h | 95.4% | 88.2% | 60.1% | 55.2% |
2h | 93.1% | 65.2% | 55.0% | 40.4% |
4h | 90.2% | 55.0% | 35.0% | 28.1% |
In addition, a comparative experiment was performed using zeaxanthin containing different isomer ratios, namely: the zeaxanthin contains two isomers of (3R, 3 'R) -zeaxanthin and (3R, 3' S) -zeaxanthin, and the weight ratio of the two isomers of the zeaxanthin is more than 80 percent; and the weight ratio between the two isomers of (3R, 3 'R) -zeaxanthin and (3R, 3' S) -zeaxanthin is 5-15%: within the range of 95-85%, the result of step (1) is not affected.
Example 2
Mixing lutein crystal 200g with 3 times of 60% ethanol water solution, stirring at 45deg.C for 30min, shearing and dispersing at 10000 r, adding ascorbic acid 20g, ascorbyl palmitate 1g, sucrose fatty acid ester 1g, removing solvent at 75deg.C, dissolving ethanol residue 7ppm, water content of the crystal 10%, and freezing at-20deg.C for use. 583g of sodium starch octenyl succinate and 195g of glucose are prepared into an aqueous solution with 50% of solid content, and after stirring and dispersing at 60 ℃, the temperature is raised to 90 ℃ and stirring is carried out at constant speed for 35min. Cooling to 60deg.C, and stirring for 100min. Mixing the gelatinized wall material with the treated lutein crystal, stirring, emulsifying, and spray drying. The lutein product A with pigment dissolution of 3.1% and release of 30.5% and 103.3% in 30min and 4h is obtained. The release rates at various times are shown in Table 2 below:
TABLE 2 Release degree at various times
Time | Degree of release | Time | Degree of release |
10min | 10.0% | 3h | 101.6% |
20min | 16.0% | 4h | 103.3% |
30min | 30.5% | 6h | 101.6% |
1h | 40.2% | 8h | 101.6% |
2h | 89.4% |
Example 3
Mixing 233g of beta carrot crystals with 5 times of 50% ethanol water solution, stirring for 40min at 40 ℃, shearing and dispersing at 10000 revolutions at high speed, adding 17g of ascorbic acid, 25.5g of ascorbyl palmitate, 25.5g of sucrose fatty acid ester, removing solvent at 70 ℃, removing 5ppm of ethanol soluble residue, keeping the water content of the crystals at 15%, and freezing at-20 ℃ for later use. 560g of sodium starch octenyl succinate and 140g of glucose are prepared into an aqueous solution with 70% of solid content, and after stirring and dispersing at 50 ℃, the temperature is raised to 80 ℃ and stirring is carried out at constant speed for 50min. Cooling to 65deg.C, and stirring for 120min. Mixing the gelatinized wall material with the treated lutein crystal, stirring, emulsifying, and spray drying. Beta carrot product A with 2.3% of pigment dissolution and 28.3% and 100.2% of release after 30min and 4h is obtained. The release rates at various times are shown in Table 3 below:
TABLE 3 Release degree at various times
Time | Degree of release | Time | Degree of release |
10min | 7.9% | 3h | 101.6% |
20min | 15.1% | 4h | 100.2% |
30min | 25.3% | 6h | 101.6% |
1h | 39.4% | 8h | 102.2% |
2h | 82.9% |
Example 4
Mixing 106g of beta carrot crystals, 212g of lutein ester crystals, 106g of zeaxanthin crystals and 4 times of 70% ethanol water solution, stirring for 55min at 50 ℃, then shearing and dispersing at 10000 revolutions at high speed, adding 73g of ascorbic acid and 1.5g of ascorbyl palmitate, 1.5g of sucrose fatty acid ester, removing the solvent at 80 ℃, removing 3ppm of ethanol soluble residue, keeping the water content of the crystals at 30%, and freezing at-20 ℃ for later use. 416.7g of sodium starch octenyl succinate and 83.3g of glucose syrup are prepared into an aqueous solution with 60% of solid content, and after stirring and dispersing at 70 ℃, the temperature is raised to 85 ℃ and stirring is carried out at constant speed for 45min. Cooling to 63 deg.C, and stirring for 130min. Mixing the gelled wall material with the treated composite crystal, stirring, emulsifying, and spray drying. Lutein ester, zeaxanthin and beta carrot 2:1:1 product A are obtained, the pigment dissolution rate is 3.5%, and the release rate is 22.4% and 99.7% after 30min and 4 h. The release rates at various times are shown in Table 4 below:
TABLE 4 Release degree at various times
Time | Degree of release | Time | Degree of release |
10min | 10.2% | 3h | 97.0% |
20min | 17.2% | 4h | 99.7% |
30min | 28.3% | 6h | 99.9% |
1h | 41.4% | 8h | 99.7% |
2h | 79.9% |
Comparative example 5
200g of beta-carotene crystal and 3 times of 60% ethanol water solution are mixed, stirred for 30min at 45 ℃, sheared and dispersed at 10000 revolutions at high speed, 20g of ascorbic acid, 1g of ascorbyl palmitate and 1g of sucrose fatty acid ester are added, the solvent is removed at 75 ℃, the ethanol solution residue is 7ppm, the water content of the crystal is 12.8%, and the crystal is frozen at-20 ℃ for standby. 583g of sodium starch octenyl succinate and 195g of glucose are prepared into an aqueous solution with 50% of solid content, stirred and dissolved at 60 ℃, the beta-carotene crystal is added, stirred, emulsified and spray dried. The beta-carotene product B is obtained, and the pigment dissolution rate is 65.8%. The release rate of the composition is 99.1% and 98.9% after 30min and 4 h.
In contrast, the wall material which is not subjected to gelation treatment has improved chromaticity and poor slow release effect.
Comparative example 6
Mixing 200g of lutein ester crystal with 3 times of 60% ethanol water solution, stirring at 45 ℃ for 30min, shearing and dispersing at 10000 r high speed, adding 20g of ascorbic acid, 1g of ascorbyl palmitate and 1g of sucrose fatty acid ester, removing solvent at 75 ℃, removing ethanol residue by 5.3ppm, keeping the water content of the crystal at 25%, and freezing at-20 ℃ for standby. 583g of sodium starch octenyl succinate and 195g of glucose are prepared into an aqueous solution with 50% of solid content, and after stirring and dispersing at 60 ℃, the temperature is raised to 100 ℃ and stirring is carried out at constant speed for 60min. Mixing the gelled wall material with the treated lutein ester crystal, stirring, emulsifying, and spray drying. The lutein ester product A with a pigment dissolution rate of 85.2% is obtained. The release rates for 30min and 4h are 97.7% and 102.3%.
In contrast, the treatment method performed under conditions other than the gelation method improved the chromaticity of the product and deteriorated the slow release effect.
Comparative example 7
200g of lutein crystal, 20g of ascorbic acid, 1g of ascorbyl palmitate and 1g of sucrose fatty acid ester are added and mixed, 583g of starch sodium octenyl succinate and 195g of glucose syrup are prepared into a 50% solid content aqueous solution, and after stirring and dispersing at 60 ℃, the temperature is raised to 90 ℃ and stirring is carried out at constant speed for 35min. Cooling to 60deg.C, and stirring for 100min. Mixing the gel wall material with the mixed lutein crystal, stirring, emulsifying, and spray drying. The lutein product B with pigment dissolution of 33.2% is obtained. The release rate of the composition is 90.1% and 95.5% after 30min and 4 h.
In contrast, the crystals were not pretreated, and the chromaticity and release of the product were both poor.
Comparative example 8
Mixing lutein crystal 200g with 3 times of 60% ethanol water solution, stirring at 45deg.C for 30min, shearing and dispersing at 10000 r, adding ascorbic acid 20g, ascorbyl palmitate 1g, sucrose fatty acid ester 1g, removing solvent at 75deg.C, dissolving ethanol residue 7ppm, water content of the crystal 10%, and freezing at-20deg.C for use. 583g of corn starch and 195g of glucose are prepared into an aqueous solution with 50% of solid content, and after stirring and dispersing at 60 ℃, the temperature is raised to 90 ℃ and stirring is carried out at constant speed for 35min. Cooling to 60deg.C, and stirring for 100min. Mixing the gelatinized wall material with the treated lutein crystal, stirring, emulsifying, and spray drying. The lutein product C is obtained, the pigment dissolution rate is 73.5%, and the release rate is 99.5% and 101.3% after 30min and 4 h.
In contrast, the replacement of sodium starch octenyl succinate with corn starch is not effective.
Effect example 9
Lutein, zeaxanthin and beta-carotene were prepared according to the method of patent 201711456450.1 in a weight ratio of 1:1:1 to obtain composite product 1, lutein, zeaxanthin and beta-carotene were obtained according to the method of example 2 in a weight ratio of 1:1:1 to obtain composite product 2, and the comparison parameters of the two products are shown in table 5 below:
table 5 comparative parameters for two products
Effect example 10: evaluation of Soft candy application
Weighing 8g of gelatin, 44g of white granulated sugar and 55g of glucose syrup, adding water with 20% of solid matters, stirring for dissolution, decocting sugar at 120 ℃, decocting until the solid matters are about 85%, and regulating the pH to 3-4; solution I was obtained.
20g of lutein product A prepared according to the method of example 2 or beta carotene product B prepared according to the method of example 5 are respectively added into the solution I and stirred uniformly. The temperature is kept at 90 ℃ for 40min. Injection molding and drying. The appearance is shown in picture 1. It can be seen that the lutein product A has no dyeing phenomenon in the soft candy and is completely stored in the soft candy, so that the nutrition visualization effect is realized. And beta-carotene product B stained the gum red and the transparency of the gum was reduced.
Effect example 11: evaluation of solid beverage applications
The lutein product a prepared by the method of example 2 and the beta-carotene product B prepared by the method of example 5 were respectively mixed with appropriate amounts of citric acid 0.03%, maltodextrin 20%, xanthan gum 0.6% and the like to prepare solid beverages, which were evaluated after brewing. As in table 6:
TABLE 6 evaluation of Effect
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and those skilled in the art can easily understand the changes and substitutions within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.
Claims (9)
1. A carotenoid preparation is characterized in that pretreated carotenoid crystals and pretreated gelled wall materials are mixed, emulsified and granulated to obtain powder or granule products;
wherein the preparation method of the pretreated carotenoid crystal comprises the following steps: mixing carotenoid crystals with 3-5 times of 50-70% ethanol water solution, stirring at 40-50deg.C for at least 20min, high-speed shearing for dispersion, adding antioxidant, removing solvent at 70-80deg.C until ethanol residue is less than 10ppm, and simultaneously water content of the crystals is 10-30%;
the antioxidant is ascorbic acid, ascorbyl palmitate and sucrose fatty acid ester according to the weight ratio of 2-5:0.1-3:0.1-3, wherein the dosage of the mixture is 5-30% of the weight of carotenoid;
the preparation method of the pretreated gelled wall material comprises the following steps: mixing the wall material and the carbohydrate according to the weight ratio of 1-5:1, preparing an aqueous solution with the solid content of 50-70%, stirring and dispersing at 50-70 ℃, stirring at 80-90 ℃ for 35-50min, cooling to 60-65 ℃ and treating for 100-150min;
the wall material is sodium starch octenyl succinate;
the carbohydrate is selected from sucrose, glucose syrup, xylose, isomaltooligosaccharide, fructooligosaccharide, solid corn syrup or a mixture thereof;
the dosage of the gelled wall material is 40-70% of the weight of the final carotenoid preparation product.
2. The carotenoid preparation according to claim 1, wherein the carotenoid is selected from lutein and fatty acid esters thereof, zeaxanthin, lycopene, alpha-carotene, beta-carotene, astaxanthin or mixtures thereof.
3. The carotenoid preparation of claim 1, wherein the carotenoid has a total pigment content of more than 80% after pretreatment.
4. A carotenoid preparation according to claim 3, wherein the carbohydrate is glucose or glucose syrup and combinations thereof.
5. A carotenoid preparation according to claim 3, wherein the weight ratio of wall material to carbohydrate is 1-3:1.
6. The carotenoid formulation of claim 1, wherein the formulation has a pigment dissolution in water of less than 5%; the release speed of the composition in gastrointestinal fluid is 0.5h < 35%, and 4h > 90%.
7. Use of a carotenoid preparation according to claim 1 in the field of food.
8. The use according to claim 7, characterized in that: the use of said carotenoid preparation for the preparation of a food requiring a visual effect of nutrients.
9. The use according to claim 7, characterized in that: the carotenoid preparation is applied to preparing soft sweets, solid beverages and liquid beverages.
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111682238.3A CN114287625B (en) | 2021-12-28 | 2021-12-28 | Carotenoid preparation and application thereof |
PCT/CN2022/142679 WO2023125626A1 (en) | 2021-12-28 | 2022-12-28 | Carotenoid preparations, preparation methods, and application thereof |
JP2023554278A JP2024509226A (en) | 2021-12-28 | 2022-12-28 | Carotenoid preparations, preparation methods, and their applications |
EP22914878.8A EP4259603A4 (en) | 2021-12-28 | 2022-12-28 | Carotenoid preparations, preparation methods, and application thereof |
US18/357,149 US20240016741A1 (en) | 2021-12-28 | 2023-07-23 | Carotenoid preparations, preparation methods, and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111682238.3A CN114287625B (en) | 2021-12-28 | 2021-12-28 | Carotenoid preparation and application thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114287625A CN114287625A (en) | 2022-04-08 |
CN114287625B true CN114287625B (en) | 2024-04-05 |
Family
ID=80975634
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111682238.3A Active CN114287625B (en) | 2021-12-28 | 2021-12-28 | Carotenoid preparation and application thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114287625B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2024509226A (en) * | 2021-12-28 | 2024-02-29 | 大▲連▼医▲諾▼生物股▲ふん▼有限公司 | Carotenoid preparations, preparation methods, and their applications |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3998753A (en) * | 1974-08-13 | 1976-12-21 | Hoffmann-La Roche Inc. | Water dispersible carotenoid preparations and processes thereof |
CN1836652A (en) * | 2005-03-23 | 2006-09-27 | 浙江新和成股份有限公司 | Water-dispersed carotenoid powder preparation method |
JP2010130903A (en) * | 2008-12-02 | 2010-06-17 | Sanei Gen Ffi Inc | Method for stabilizing carotenoid pigment |
CN103284290A (en) * | 2013-05-24 | 2013-09-11 | 肇庆巨元生化有限公司 | Good microencapsulation method for carotenoid |
CN108185424A (en) * | 2017-12-28 | 2018-06-22 | 大连医诺生物股份有限公司 | Carotenoid microparticle formulation and preparation method thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2261456A1 (en) * | 1998-02-23 | 1999-08-23 | F. Hoffmann-La Roche Ag | Preparation of a finely divided pulverous carotenoid preparation |
CN101549273B (en) * | 2009-03-30 | 2011-06-15 | 浙江新和成股份有限公司 | Method of preparing nano-dispersed high-all-trans-carotenoid microcapsules |
-
2021
- 2021-12-28 CN CN202111682238.3A patent/CN114287625B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3998753A (en) * | 1974-08-13 | 1976-12-21 | Hoffmann-La Roche Inc. | Water dispersible carotenoid preparations and processes thereof |
CN1836652A (en) * | 2005-03-23 | 2006-09-27 | 浙江新和成股份有限公司 | Water-dispersed carotenoid powder preparation method |
JP2010130903A (en) * | 2008-12-02 | 2010-06-17 | Sanei Gen Ffi Inc | Method for stabilizing carotenoid pigment |
CN103284290A (en) * | 2013-05-24 | 2013-09-11 | 肇庆巨元生化有限公司 | Good microencapsulation method for carotenoid |
CN108185424A (en) * | 2017-12-28 | 2018-06-22 | 大连医诺生物股份有限公司 | Carotenoid microparticle formulation and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
CN114287625A (en) | 2022-04-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US3206316A (en) | Water dispersible carotenoid preparations and processes thereof | |
CN101177540B (en) | Method for preparing lutein water-soluble dry powder | |
CN102578346B (en) | Lutein ester soft sweet and preparation method thereof | |
US5976575A (en) | Dry carotenoid-oil powder and process for making same | |
EP0986963B1 (en) | Stable, powdery lycopene formulations containing lycopene with a degree of crystallisation of more than 20% | |
US8765186B2 (en) | Process for the manufacture of a powder containing carotenoids | |
US2861891A (en) | Water dispersible carotenoid compositions and process of making the same | |
US3655406A (en) | Carotenoid compositions | |
US20200029596A1 (en) | Fat-soluble nutrient microcapsule and preparation method thereof | |
DE19637517A1 (en) | Production of powdered, cold water dispersible carotenoid preparations and the use of the new carotenoid preparations | |
NO320106B1 (en) | Stable aqueous dispersions and stable, water dispersible dry powder of xanthophyll compounds, as well as processes for their preparation and use. | |
JPH0366615A (en) | Manufacture of new colloid dispersion carotinoid preparation | |
CN108208815A (en) | Blueberry and the double-colored composite sheet of lutein ester and preparation method thereof | |
CN111035015B (en) | Non-water-soluble fat-soluble nutrient microcapsule and preparation method thereof | |
CN114287625B (en) | Carotenoid preparation and application thereof | |
CN109452467A (en) | A kind of type vitamin A microcapsules and its preparation method and application | |
DE60223569T2 (en) | ZEACAROTENE PAINTING FOR FOOD OR PHARMACEUTICALS | |
CN114276285B (en) | Carotenoid preparation, preparation method and application thereof | |
CN108148444A (en) | A kind of high-content beta carotene microcapsules for being used for coloring and preparation method thereof | |
CN112167615B (en) | Hydrophobic fat-soluble nutrient microcapsule and preparation method thereof | |
CN112515088B (en) | Water-dispersible lutein ester preparation and preparation method and application thereof | |
JP2006516396A (en) | Novel compositions containing carotenoids | |
JP2000106844A (en) | Water-dispersible carotenoid composition | |
CN105072926B (en) | It is suitble to the lutein composition of infant food preparation | |
CN111480756A (en) | Theaflavin composition for relieving asthenopia and preparation method thereof |
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 |