JPH11236331A - Vitamin as-solubilized preparation - Google Patents
Vitamin as-solubilized preparationInfo
- Publication number
- JPH11236331A JPH11236331A JP5623698A JP5623698A JPH11236331A JP H11236331 A JPH11236331 A JP H11236331A JP 5623698 A JP5623698 A JP 5623698A JP 5623698 A JP5623698 A JP 5623698A JP H11236331 A JPH11236331 A JP H11236331A
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- solubilized
- preparation
- acid
- stabilizer
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 100
- 229940088594 vitamin Drugs 0.000 title claims description 8
- 229930003231 vitamin Natural products 0.000 title claims description 8
- 235000013343 vitamin Nutrition 0.000 title claims description 8
- 239000011782 vitamin Substances 0.000 title claims description 8
- 150000003722 vitamin derivatives Chemical class 0.000 title claims description 6
- 235000019155 vitamin A Nutrition 0.000 claims abstract description 128
- 239000011719 vitamin A Substances 0.000 claims abstract description 128
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims abstract description 125
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims abstract description 125
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims abstract description 125
- 229940045997 vitamin a Drugs 0.000 claims abstract description 125
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 claims abstract description 47
- 239000003381 stabilizer Substances 0.000 claims abstract description 26
- 239000007864 aqueous solution Substances 0.000 claims abstract description 21
- 239000002245 particle Substances 0.000 claims abstract description 21
- 230000000694 effects Effects 0.000 claims abstract description 20
- 239000004094 surface-active agent Substances 0.000 claims abstract description 17
- 229920000137 polyphosphoric acid Polymers 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 230000003381 solubilizing effect Effects 0.000 claims abstract description 4
- -1 polyoxyethylene Polymers 0.000 claims description 20
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 239000004359 castor oil Substances 0.000 claims description 11
- 235000019438 castor oil Nutrition 0.000 claims description 11
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 8
- 239000011975 tartaric acid Substances 0.000 claims description 8
- 235000002906 tartaric acid Nutrition 0.000 claims description 8
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 6
- 229920000053 polysorbate 80 Polymers 0.000 claims description 6
- 229940068968 polysorbate 80 Drugs 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- 239000003995 emulsifying agent Substances 0.000 claims description 5
- 229920000388 Polyphosphate Polymers 0.000 claims description 4
- 239000001205 polyphosphate Substances 0.000 claims description 4
- 235000011176 polyphosphates Nutrition 0.000 claims description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims 1
- 235000011180 diphosphates Nutrition 0.000 claims 1
- 125000005341 metaphosphate group Chemical group 0.000 claims 1
- 150000002266 vitamin A derivatives Chemical class 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 6
- 230000000087 stabilizing effect Effects 0.000 abstract description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 abstract 1
- 239000003921 oil Substances 0.000 description 27
- 235000019198 oils Nutrition 0.000 description 27
- 239000012071 phase Substances 0.000 description 21
- 235000015097 nutrients Nutrition 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000008346 aqueous phase Substances 0.000 description 13
- 230000000052 comparative effect Effects 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 11
- 239000003963 antioxidant agent Substances 0.000 description 10
- 230000003078 antioxidant effect Effects 0.000 description 10
- 235000006708 antioxidants Nutrition 0.000 description 10
- 235000016709 nutrition Nutrition 0.000 description 10
- 239000008213 purified water Substances 0.000 description 9
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 6
- 235000015872 dietary supplement Nutrition 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 238000000265 homogenisation Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000035764 nutrition Effects 0.000 description 5
- MOMKYJPSVWEWPM-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-methylphenyl)-1,3-thiazole Chemical compound C1=CC(C)=CC=C1C1=NC(CCl)=CS1 MOMKYJPSVWEWPM-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 4
- 238000004945 emulsification Methods 0.000 description 4
- 239000003925 fat Substances 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000005191 phase separation Methods 0.000 description 4
- 235000013772 propylene glycol Nutrition 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- 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 4
- 235000019983 sodium metaphosphate Nutrition 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- 229930003448 Vitamin K Natural products 0.000 description 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 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
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 3
- 229940005657 pyrophosphoric acid Drugs 0.000 description 3
- 229960000342 retinol acetate Drugs 0.000 description 3
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 3
- 235000019173 retinyl acetate Nutrition 0.000 description 3
- 239000011770 retinyl acetate Substances 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 238000012360 testing method Methods 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
- 235000019168 vitamin K Nutrition 0.000 description 3
- 239000011712 vitamin K Substances 0.000 description 3
- 150000003721 vitamin K derivatives Chemical class 0.000 description 3
- 229940046010 vitamin k Drugs 0.000 description 3
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 2
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- VYGQUTWHTHXGQB-UHFFFAOYSA-N Retinol hexadecanoate Natural products CCCCCCCCCCCCCCCC(=O)OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 229930003316 Vitamin D Natural products 0.000 description 2
- 150000004347 all-trans-retinol derivatives Chemical class 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 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
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 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 2
- 230000006866 deterioration Effects 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 235000019175 phylloquinone Nutrition 0.000 description 2
- 239000011772 phylloquinone Substances 0.000 description 2
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 description 2
- 229960001898 phytomenadione Drugs 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 229940108325 retinyl palmitate Drugs 0.000 description 2
- 235000019172 retinyl palmitate Nutrition 0.000 description 2
- 239000011769 retinyl palmitate Substances 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
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- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229940042585 tocopherol acetate Drugs 0.000 description 2
- 235000019166 vitamin D Nutrition 0.000 description 2
- 239000011710 vitamin D Substances 0.000 description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 description 2
- 229940046008 vitamin d Drugs 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-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
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 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
- 239000004380 Cholic acid Substances 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
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- 235000015278 beef Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
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- 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
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- 235000019868 cocoa butter Nutrition 0.000 description 1
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- 239000003240 coconut oil Substances 0.000 description 1
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- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
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- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[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 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 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
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000001726 jatropha manihot extract Substances 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 235000020640 mackerel Nutrition 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 235000019512 sardine Nutrition 0.000 description 1
- 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 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 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 1
- 229940100515 sorbitan Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 229940048102 triphosphoric acid Drugs 0.000 description 1
- 229940035936 ubiquinone Drugs 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229940106668 yucca extract Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【０００１】[0001]
【発明が属する技術分野】本発明は、ビタミンＡ類可溶
化製剤、特に栄養剤等に配合することを目的としたビタ
ミンＡ類可溶化製剤であって、栄養剤等に添加して用い
てもビタミンＡ類はその活性を失わず、可溶化状態を安
定に長期間保持することができるビタミンＡ類可溶化製
剤に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solubilized preparation of vitamin A, particularly a solubilized preparation of vitamin A intended to be incorporated into a nutrient or the like. The present invention relates to a vitamin A-solubilized preparation which does not lose its activity and can stably maintain a solubilized state for a long period of time.
【０００２】[0002]
【従来の技術】ビタミンＡおよびその誘導体等ビタミン
Ａ活性を有するビタミンＡ類は、栄養ドリンク剤、経腸
栄養剤または輸液栄養剤等の各種栄養剤、食品等に配合
される場合がある。ところが、脂溶性のビタミンＡ類は
非常に酸化され易く、特に水溶液中では極めて不安定で
あり、酸、光、熱等により種々の異性化、分解を生じて
しまう。2. Description of the Related Art Vitamin A having vitamin A activity such as vitamin A and its derivatives may be blended in various nutrients such as nutritional drinks, enteral nutrients or infusion nutrients, foods and the like. However, fat-soluble vitamin A is very easily oxidized, and is particularly unstable in an aqueous solution, and causes various isomerizations and decompositions by acid, light, heat and the like.
【０００３】そこで、栄養剤等に添加して用いられても
ビタミンＡ類の活性が失われず、安定な状態を長期間維
持することができるビタミンＡ類含有水性製剤の開発が
望まれていた。[0003] Therefore, there has been a demand for the development of a vitamin A-containing aqueous preparation which does not lose the activity of vitamin A even when used as a nutrient or the like and can maintain a stable state for a long period of time.
【０００４】これまでのビタミンＡ類の安定化技術とし
ては、坑酸化剤を使用する方法が知られている。例え
ば、ジブチルヒドロキシトルエン（ＢＨＴ）およびブチ
ルヒドロキシアニソール（ＢＨＡ）などの脂溶性抗酸化
剤や、アスコルビン酸、ヒドロキノンおよびシステイン
などの水溶性抗酸化剤を添加する方法（特開昭５８−４
１８１３号公報）が提案されている。[0004] As a conventional technique for stabilizing vitamin A, a method using an antioxidant is known. For example, a method of adding a fat-soluble antioxidant such as dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA) and a water-soluble antioxidant such as ascorbic acid, hydroquinone and cysteine (Japanese Patent Application Laid-Open No. 58-4)
No. 1813).
【０００５】また、非イオン界面活性剤により可溶化し
たビタミンＡ類を、脂溶性抗酸化剤、水溶性抗酸化剤お
よび特定アミノ酸の３群中のうち少なくとも２群の化合
物を配合し、ビタミンＡ類を安定化する方法（特開平５
−１７３５０）が提案されている。[0005] Vitamin A solubilized by a nonionic surfactant is compounded with at least two compounds out of three groups of a fat-soluble antioxidant, a water-soluble antioxidant and a specific amino acid. To stabilize the odorous substances (JP-A-5
-17350) has been proposed.
【０００６】しかし、これらの方法によれば、ビタミン
Ａ類を添加配合した栄養剤等は、抗酸化剤の抗酸化速度
よりもビタミンＡ類の酸化速度の方が速く、長期間に亘
る保存の場合、栄養剤中のビタミンＡ類の活性が損なわ
れるおそれがあり、十分に満足し得るものではなかっ
た。However, according to these methods, nutrients and the like to which vitamin A is added and mixed have a higher oxidation rate of vitamin A than the antioxidant of the antioxidant, and can be stored for a long period of time. In such a case, the activity of vitamin A in the nutritional supplement may be impaired, and it has not been sufficiently satisfactory.
【０００７】また、特定のＨＬＢ値のポリオキシエチレ
ン硬化ヒマシ油に、異なる特定のＨＬＢ値の非イオン界
面活性剤を組合わせることによりビタミンＡ類の不安定
化を防止し、長期にわたって外観を安定に維持する方法
（特開平５−３３１０５６）が提案されている。Further, by combining a polyoxyethylene hydrogenated castor oil having a specific HLB value with a nonionic surfactant having a different specific HLB value, the destabilization of vitamins A is prevented, and the appearance is stabilized for a long period of time. (Japanese Patent Laid-Open No. 5-331506) has been proposed.
【０００８】しかし、この方法で調製されたビタミンＡ
類可溶化水溶液は、外観の安定性は保持できるが、ビタ
ミンＡ類は活性を十分保持し得るものではなく、ビタミ
ンＡ類を長期間安定に維持し得るビタミンＡ類可溶化製
剤は実用化されていなかった。However, vitamin A prepared by this method
Aqueous solubilized aqueous solution can maintain the stability of appearance, but vitamin A can not maintain sufficient activity, and a vitamin A solubilized preparation that can maintain vitamin A stably for a long time has been put to practical use. I didn't.
【０００９】[0009]
【発明が解決しようとする課題】本発明の目的は、栄養
剤等に添加してもビタミンＡ類は活性を失わず、長期間
安定な可溶化状態を維持することができるビタミンＡ類
可溶化製剤を提供することにある。SUMMARY OF THE INVENTION An object of the present invention is to provide a solubilized vitamin A which can maintain a stable solubilized state for a long time without losing its activity even when added to a nutrient or the like. It is to provide a formulation.
【００１０】[0010]
【課題を解決するための手段】このような目的は、下記
（１）〜（９）の本発明により達成される。This and other objects are achieved by the present invention which is defined below as (1) to (9).
【００１１】（１） ビタミンＡ活性を有するビタミン
Ａ類と、前記ビタミンＡ類を水溶液に可溶化させる界面
活性剤と、前記ビタミンＡ類を前記水溶液中で安定に存
在させる安定化剤とを含有するビタミンＡ類可溶化製剤
であって、前記水溶液における前記ビタミンＡ類の平均
粒径が５０nm以下であることを特徴とするビタミンＡ類
可溶化製剤。(1) Vitamin A having vitamin A activity, a surfactant for solubilizing the vitamin A in an aqueous solution, and a stabilizer for stably presenting the vitamin A in the aqueous solution are contained. A solubilized vitamin A preparation, wherein the average particle size of the vitamin A in the aqueous solution is 50 nm or less.
【００１２】（２） 前記ビタミンＡ類の含有量が０．
０１〜７ W/V％である上記（１）に記載のビタミンＡ類
可溶化製剤。(2) The content of the vitamin A is in the range of 0.
The vitamin A-solubilized preparation according to the above (1), wherein the preparation is 0.01 to 7 W / V%.
【００１３】（３） 前記安定化剤はオキシカルボン酸
およびオキシカルボン酸塩のうち少なくとも１つである
上記（１）または（２）に記載のビタミンＡ類可溶化製
剤。(3) The vitamin A-solubilized preparation according to the above (1) or (2), wherein the stabilizer is at least one of oxycarboxylic acid and oxycarboxylic acid salt.
【００１４】（４） 前記オキシカルボン酸はクエン酸
および酒石酸のうち少なくとも１つである上記（３）に
記載のビタミンＡ類可溶化製剤。(4) The vitamin A-solubilized preparation according to the above (3), wherein the oxycarboxylic acid is at least one of citric acid and tartaric acid.
【００１５】（５） 前記安定化剤はポリリン酸および
ポリリン酸塩のうち少なくとも１つである上記（１）な
いし（４）のいずれかに記載のビタミンＡ類可溶化製
剤。(5) The solubilized vitamin A preparation according to any one of the above (1) to (4), wherein the stabilizer is at least one of polyphosphoric acid and polyphosphate.
【００１６】（６） 前記ポリリン酸はメタリン酸およ
びピロリン酸のうち少なくとも１つである上記（５）に
記載のビタミンＡ類可溶化製剤。(6) The vitamin A-solubilized preparation according to the above (5), wherein the polyphosphoric acid is at least one of metaphosphoric acid and pyrophosphoric acid.
【００１７】（７） 前記安定化剤の含有量が０．０２
〜０．７ W/V％である上記（１）ないし（６）のいずれ
かに記載のビタミンＡ類可溶化製剤。(7) The content of the stabilizer is 0.02
The vitamin A solubilized preparation according to any one of the above (1) to (6), wherein the preparation has a concentration of 〜0.7 W / V%.
【００１８】（８） 前記乳化剤はポリソルベート８０
およびポリキシエチレン硬化ヒマシ油６０のうち少なく
とも１つである上記（７）に記載のビタミンＡ類可溶化
製剤。(8) The emulsifier is polysorbate 80
And the solubilized preparation of vitamin A according to the above (7), which is at least one of polyoxyethylene hydrogenated castor oil 60.
【００１９】（９） 前記界面活性剤の含有量が０．５
〜２０ W/V％である上記（１）ないし（８）のいずれか
に記載のビタミンＡ類可溶化製剤。(9) The surfactant content is 0.5
The vitamin A-solubilized preparation according to any one of the above (1) to (8), which has a W20 W / V%.
【００２０】[0020]
【発明の実施の形態】以下、本発明のビタミンＡ類可溶
化製剤を好適実施例に基づいて詳細に説明する。BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the solubilized preparation of vitamin A of the present invention will be described in detail based on preferred embodiments.
【００２１】本発明のビタミンＡ類可溶化製剤は、ビタ
ミンＡ活性を有するビタミンＡ類と、ビタミンＡ類を水
溶液に可溶化させる界面活性剤と、ビタミンＡ類を水溶
液中で安定に存在させる安定化剤とを含有するものであ
って、前記ビタミンＡ類の平均粒径が５０nm以下である
ことを特徴とする。The solubilized preparation of vitamin A of the present invention comprises a vitamin A having a vitamin A activity, a surfactant for solubilizing the vitamin A in an aqueous solution, and a stable agent in which the vitamin A is stably present in the aqueous solution. An average particle size of the vitamin A is 50 nm or less.
【００２２】ビタミンＡ類の平均粒径が５０nm以下であ
ることにより、脂溶性であるビタミンＡ類が水溶液中に
おいて良好に分散し、安定に存在することができる。ま
た、栄養ドリンク剤、経腸栄養剤または輸液栄養剤等の
栄養剤および食品等に配合し、長期間保存してもビタミ
ンＡ類が分離したりすることなく、安定な可溶化状態を
保つことができる。When the average particle diameter of the vitamin A is 50 nm or less, the fat-soluble vitamin A can be well dispersed in the aqueous solution and can be stably present. In addition, it is blended in nutritional drinks, enteral nutrition, nutritional supplements such as infusion nutrients and foods, etc., and keeps a stable solubilized state without separation of vitamin A even after long-term storage. Can be.
【００２３】ここで、ビタミンＡ類の安定化とは、水溶
液中でビタミンＡ活性が損なわれることがなく、かつ相
分離等を生じないで長期間安定に存在し得ることを意味
し、例えばビタミンＡ類可溶化製剤を調製した直後のビ
タミンＡ類の活性（含有量）に対し、各条件下で保存し
た場合にビタミンＡ類の活性（含有量）が９０％以上残
存し、さらにビタミンＡ類の平均粒径が変化していない
状態等をいう。The term "stabilization of vitamin A" as used herein means that vitamin A activity is not impaired in an aqueous solution and can be stably present for a long period of time without causing phase separation or the like. The activity (content) of vitamin A immediately after the preparation of the solubilized preparation A is 90% or more of the activity (content) of vitamin A when stored under each condition. Mean that the average particle size has not changed.
【００２４】また、ビタミンＡ類の可溶化とは、ビタミ
ンＡ類を含有する溶液系が均一で透明であり、例えば溶
液中にビタミンＡ類の平均粒径が５０nm以下となって存
在している状態を意味する。The solubilization of vitamin A means that the solution system containing vitamin A is uniform and transparent, for example, the solution has an average particle diameter of 50 nm or less in the solution. Means the state.
【００２５】本発明に用いられるビタミンＡ類は、ビタ
ミンＡおよびビタミンＡ誘導体等のビタミンＡ活性を有
するものであればいかなるものであってもよく、一般に
ビタミンＡ、ビタミンＡ油等のビタミンＡ含有混合物、
ビタミンＡパルミテート、ビタミンＡアセテート等のビ
タミンＡ脂肪酸エステル等、およびそれらの誘導体等が
挙げられる。The vitamin A used in the present invention may be any one having vitamin A activity such as vitamin A and vitamin A derivatives, and generally contains vitamin A such as vitamin A and vitamin A oil. blend,
Examples include vitamin A fatty acid esters such as vitamin A palmitate and vitamin A acetate, and derivatives thereof.
【００２６】本発明のビタミンＡ類可溶化製剤中のビタ
ミンＡ類の含有量は、０．０１〜７W/V％が好ましく、
０．０５〜５ W/V％がより好ましい。ビタミンＡ類の含
有量が０．０１ W/V％未満であると、ビタミンＡ類の十
分な活性が得られないおそれがあり、７ W/V％を超える
場合ビタミンＡ類を安定に可溶化することが困難となる
場合がある。The content of vitamin A in the solubilized preparation of vitamin A of the present invention is preferably 0.01 to 7 W / V%,
0.05-5 W / V% is more preferable. If the content of vitamin A is less than 0.01 W / V%, sufficient activity of vitamin A may not be obtained, and if it exceeds 7 W / V%, vitamin A is stably solubilized. May be difficult to do.
【００２７】本発明のビタミンＡ類可溶化製剤は、ビタ
ミンＡ類を水溶液中で安定に存在させる安定化剤を含有
する。これによりビタミンＡ類は水溶液中においても長
期間安定な状態を維持することができる。The solubilized preparation of vitamin A of the present invention contains a stabilizing agent which makes the vitamin A exist stably in an aqueous solution. Thereby, vitamin A can maintain a stable state for a long time even in an aqueous solution.
【００２８】本発明において使用されるビタミンＡ類の
安定化剤としては、例えばオキシカルボン酸およびオキ
シカルボン酸塩のうち少なくとも１つであることが好ま
しい。The stabilizer for vitamin A used in the present invention is preferably, for example, at least one of oxycarboxylic acid and oxycarboxylic acid salt.
【００２９】オキシカルボン酸としては、クエン酸、酒
石酸、グルコン酸等が挙げられるが、なかでもクエン酸
および酒石酸のうち少なくとも１つであることがより好
ましく、これらは１種または２種以上を混合して使用す
ることができる。これにより、上記ビタミンＡ類の安定
化効果をより効果的に発揮させることができる。Examples of the oxycarboxylic acid include citric acid, tartaric acid, gluconic acid and the like. Among them, at least one of citric acid and tartaric acid is more preferable, and one or more of these are mixed. Can be used. Thereby, the stabilizing effect of the vitamin A can be exhibited more effectively.
【００３０】さらにこれらの塩としては、例えばナトリ
ウム塩、カリウム塩等が挙げられる。Further, examples of these salts include sodium salts and potassium salts.
【００３１】また、安定化剤はポリリン酸およびポリリ
ン酸塩のうち少なくとも１つであることが好ましい。ポ
リリン酸としては、例えばピロリン酸、メタリン酸、ト
リリン酸等が挙げられ、これらを１種または２種以上を
混合して使用することができるが、なかでもメタリン
酸、ピロリン酸が特に好ましい。これにより、上記と同
様、ビタミンＡ類の安定化効果をより有効に発揮させる
ことができる。Further, the stabilizer is preferably at least one of polyphosphoric acid and polyphosphate. Examples of the polyphosphoric acid include pyrophosphoric acid, metaphosphoric acid, and triphosphoric acid. These can be used alone or in combination of two or more. Among them, metaphosphoric acid and pyrophosphoric acid are particularly preferable. Thereby, similarly to the above, the stabilizing effect of vitamin A can be exhibited more effectively.
【００３２】また、これらの塩としては、例えばナトリ
ウム塩、カリウム塩等が挙げられる。[0032] Examples of these salts include sodium salts and potassium salts.
【００３３】上記オキシカルボン酸またはポリリン酸お
よびこれらの塩等に代表される安定化剤の含有量は、
０．０２〜０．７ W/V％が好ましく、０．０５〜０．５
W/V％がより好ましい。含有量が０．０２ W/V％未満の
場合、ビタミンＡ類の安定性向上効果が得られ難く、一
方、０．７ W/V％を超えてもビタミンＡ類の安定性の向
上は殆どみられない。The content of the stabilizer represented by the above oxycarboxylic acid or polyphosphoric acid and salts thereof is as follows:
0.02 to 0.7 W / V% is preferable, and 0.05 to 0.5
W / V% is more preferred. When the content is less than 0.02 W / V%, the effect of improving the stability of vitamin A is difficult to be obtained. On the other hand, even when the content exceeds 0.7 W / V%, the stability of vitamin A is hardly improved. I can't see it.
【００３４】本発明のビタミンＡ類可溶化製剤は界面活
性剤を含有する。これにより脂溶性のビタミンＡ類を水
溶液中に良好に分散させ、安定に可溶化することができ
る。[0034] The solubilized preparation of vitamin A of the present invention contains a surfactant. Thereby, fat-soluble vitamin A can be satisfactorily dispersed in the aqueous solution and can be solubilized stably.
【００３５】界面活性剤としては、医薬製剤に使用され
るものであれば特に限定されず、例えば、高度精製卵黄
レシチン、精製大豆レシチン、精製卵黄レシチン、セス
キオレイン酸ソルビタン、ソルビタン脂肪酸エステル、
ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレン
硬化ヒマシ油５０、ポリオキシエチレン硬化ヒマシ油６
０、ポリオキシエチレンソルビタンモノラウレート、ポ
リオキシエチレンヒマシ油、ポリオキシエチレン（１６
０）ポリオキシプロピレン（３０）グリコール、ポリソ
ルベート８０、モノラウリン酸ポリオキシエチレンソル
ビタン（２０Ｅ． O．）、グリセリン脂肪酸エステル、
プロピレングリコール脂肪酸エステル、ショ糖脂肪酸エ
ステル等が挙げられ、これらを１種または２種以上混合
して使用することができる。これらのなかでも、ポリソ
ルベート８０またはポリオキシエチレン硬化ヒマシ油６
０を使用することが特に好ましい。これにより、ビタミ
ンＡ類をより良好に分散し、安定に可溶化することがで
きる。The surfactant is not particularly limited as long as it is used for a pharmaceutical preparation. For example, highly purified egg yolk lecithin, purified soybean lecithin, purified egg yolk lecithin, sorbitan sesquioleate, sorbitan fatty acid ester,
Polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 6
0, polyoxyethylene sorbitan monolaurate, polyoxyethylene castor oil, polyoxyethylene (16
0) polyoxypropylene (30) glycol, polysorbate 80, polyoxyethylene sorbitan monolaurate (20EO), glycerin fatty acid ester,
Propylene glycol fatty acid esters, sucrose fatty acid esters and the like can be mentioned, and these can be used alone or in combination of two or more. Among these, polysorbate 80 or polyoxyethylene hydrogenated castor oil 6
It is particularly preferred to use 0. As a result, the vitamin A can be more favorably dispersed and stably solubilized.
【００３６】さらに、これらの界面活性剤を上記安定化
剤としてオキシカルボン酸、ポリリン酸およびそれらの
塩等のうち少なくとも１つと組合わせることにより、よ
り一層効果的にビタミンＡ類の安定化を図ることができ
る。Furthermore, by combining these surfactants with at least one of oxycarboxylic acid, polyphosphoric acid and their salts as the above-mentioned stabilizer, the stabilization of vitamins A can be achieved more effectively. be able to.
【００３７】界面活性剤の含有量は、０．５〜２０ W/V
％が好ましく、１．０〜１５ W/V％がより好ましい。界
面活性剤の含有量が０．５ W/V％よりも少ない場合、ビ
タミンＡ類を可溶化し安定に維持することが困難になる
場合がある。一方、２０ W/V％を超えてもビタミンＡ類
の可溶化の向上はみられない場合がある。The content of the surfactant is 0.5 to 20 W / V
%, More preferably 1.0 to 15 W / V%. When the content of the surfactant is less than 0.5 W / V%, it may be difficult to solubilize and maintain stable vitamin A's. On the other hand, even if it exceeds 20 W / V%, improvement in solubilization of vitamin A may not be observed.
【００３８】なお、本発明のビタミンＡ類可溶化製剤
は、上記ビタミンＡ類のみならず、他の脂溶性ビタミン
や油脂類を含むものであってもよい。混合可能な脂溶性
ビタミンとしては、例えばビタミンＤ、ビタミンＥ、ビ
タミンＦ、ビタミンＫ、ユビキノンおよびこれらの活性
を有する誘導体、混合物等が挙げられる。The vitamin A-solubilized preparation of the present invention may contain not only the above-mentioned vitamin A but also other fat-soluble vitamins and fats and oils. Examples of fat-soluble vitamins that can be mixed include vitamin D, vitamin E, vitamin F, vitamin K, ubiquinone, and derivatives and mixtures thereof having an activity thereof.
【００３９】また、混合可能な油脂類としては、一般に
動物、植物、または微生物を原料とする油脂が挙げら
れ、例えば、豚脂、牛脂、鶏油、マグロ油、イワシ油、
サバ油、肝油、大豆油、綿実油、サフラワー油、米油、
コーン油、ナタネ油、パーム油、シソ油、カカオ脂、落
花生油、ヤシ油等が挙げられる。さらに、中鎖脂肪酸ト
リグリセリドなどの合成トリグリセリドなどが挙げられ
る。これらを１種または２種以上適宜組み合わせて使用
することができる。Examples of the fats and oils which can be mixed include fats and oils which are generally made from animals, plants or microorganisms, such as lard, beef tallow, chicken oil, tuna oil, sardine oil, and the like.
Mackerel oil, liver oil, soybean oil, cottonseed oil, safflower oil, rice oil,
Corn oil, rapeseed oil, palm oil, perilla oil, cocoa butter, peanut oil, coconut oil, and the like. Furthermore, synthetic triglycerides such as medium chain fatty acid triglycerides and the like can be mentioned. These can be used alone or in combination of two or more.
【００４０】さらに、本発明のビタミンＡ可溶化製剤に
は、性質を損なわない範囲において乳化剤、乳化助剤、
安定化剤等を１種または２種以上組合わせて添加しても
よい。Furthermore, the vitamin A solubilized preparation of the present invention contains an emulsifier, an emulsifying aid, and
A stabilizer or the like may be added alone or in combination of two or more.
【００４１】乳化剤としては、例えば、サポニン、ステ
ロール、コール酸、デソキシコール酸、ユッカ抽出物等
が挙げられる。乳化助剤としては、例えば、ブドウ糖、
果糖、ショ糖、乳糖、麦芽糖、デキストリン、プロピレ
ングリコール、グリセリンや糖アルコール、例えば、マ
ルチトール、還元水あめ、ラクチトール、パラチニッ
ト、エリスリトール、ソルビトール、マンニトール、キ
シリトール等が挙げられる。その他の安定化剤として
は、例えばアラビアガム、キサンタンガム、トラガント
ガム、グアガム、ジェランガム、ローカストビーンガム
等のガム質等が挙げられる。Examples of the emulsifier include saponin, sterol, cholic acid, desoxycholic acid, Yucca extract and the like. As the emulsifying aid, for example, glucose,
Examples include fructose, sucrose, lactose, maltose, dextrin, propylene glycol, glycerin and sugar alcohols such as maltitol, reduced starch syrup, lactitol, palatinit, erythritol, sorbitol, mannitol, xylitol and the like. Examples of other stabilizers include gums such as gum arabic, xanthan gum, tragacanth gum, guar gum, gellan gum, and locust bean gum.
【００４２】このようにして得られたビタミンＡ類可溶
化製剤は、栄養ドリンク剤、経腸栄養剤または輸液栄養
剤等の各種栄養剤、食品等に配合して使用される。その
場合であっても長期間保存してもビタミンＡ類の活性が
失われず、安定な可溶化状態を保つことができる。The solubilized preparation of vitamin A thus obtained is used by blending it with various nutrients such as nutritional drinks, enteral nutrients or infusion nutrients, foods and the like. Even in this case, even if stored for a long period of time, the activity of vitamin A is not lost, and a stable solubilized state can be maintained.
【００４３】本発明のビタミンＡ可溶化製剤は、例えば
以下のような方法で調製することができる。The vitamin A solubilized preparation of the present invention can be prepared, for example, by the following method.
【００４４】まず、界面活性剤とビタミンＡ類を油脂等
に溶解させ、プロペラ式攪拌機やホモミキサー等の攪拌
機を用いてよく混合し油相を調製する。First, a surfactant and vitamin A are dissolved in fats and oils and mixed well using a stirrer such as a propeller stirrer or a homomixer to prepare an oil phase.
【００４５】これとは別に、水（精製水）と安定化剤と
を攪拌機等を用いて混合・溶解し水相を調製する。ここ
に、先の界面活性剤とビタミンＡ類とを含む油相を攪拌
しながら徐々に加えていく。このとき、逆に油相に水相
を加えてもよい。Separately, water (purified water) and a stabilizer are mixed and dissolved using a stirrer or the like to prepare an aqueous phase. Here, the oil phase containing the surfactant and the vitamin A is gradually added with stirring. At this time, a water phase may be added to the oil phase.
【００４６】このような工程によりビタミンＡ類可溶化
製剤は調製されるが、油相が十分に可溶化されていない
場合には、さらに高圧ホモジナイザー、超高圧ホモジナ
イザー、マイクロフルイダイザー、ナノマイザー、アル
ティマイザー等の均質化処理機を用いた均質化処理を行
ってもよい。これにより、容易かつ確実に均一に可溶化
したビタミンＡ類可溶化製剤を得ることができる。A vitamin A-solubilized preparation is prepared by such a process, but if the oil phase is not sufficiently solubilized, a high-pressure homogenizer, an ultra-high-pressure homogenizer, a microfluidizer, a nanomizer, an ultimizer is used. Or the like, using a homogenization processor. This makes it possible to easily and surely obtain a uniformly solubilized vitamin A preparation.
【００４７】この均質化処理は、可溶化状態の安定性向
上のため、複数回行ってもよい。また、均質化処理とし
ては、前述した均質化処理機を用いる方法以外に、超音
波乳化機等を用いることができ、その他転相乳化法、液
晶乳化法、Ｄ相乳化法およびＰＩＴ乳化法等によること
もできる。This homogenization treatment may be performed plural times in order to improve the stability of the solubilized state. As the homogenization treatment, in addition to the above-mentioned method using the homogenizer, an ultrasonic emulsifier can be used, and other methods such as phase inversion emulsification, liquid crystal emulsification, D-phase emulsification, and PIT emulsification can be used. It can also be.
【００４８】さらに、本発明のビタミンＡ類可溶化製剤
は、６０〜１００℃で殺菌処理が行われ、さらに必要に
応じて１００〜１５０℃の高温殺菌または滅菌処理を経
て保管または使用される。Further, the solubilized preparation of vitamin A of the present invention is sterilized at 60 to 100 ° C., and if necessary, is stored or used after being subjected to high-temperature sterilization or sterilization at 100 to 150 ° C.
【００４９】本発明のビタミンＡ類可溶化製剤は、栄養
ドリンク剤、経腸栄養剤または輸液栄養剤等の栄養剤に
配合された後、６０〜１００℃で殺菌処理が行われ、さ
らに必要に応じて１００〜１５０℃高温殺菌または滅菌
処理が行われるが、このような加熱処理に対しても安定
であり、また長期間保存してもビタミンＡ類が分解等に
より失われたり、相分離を生じたりすることなく安定に
可溶化状態を保つことができる。The vitamin A-solubilized preparation of the present invention is added to nutrients such as nutritional drinks, enteral nutrients or infusion nutrients, and then sterilized at 60 to 100 ° C. High-temperature sterilization or sterilization treatment is performed at 100 to 150 ° C. depending on the conditions. However, it is stable against such a heat treatment, and vitamin A is lost due to decomposition or the like even after long-term storage. The solubilized state can be stably maintained without any occurrence.
【００５０】以上、本発明のビタミンＡ類可溶化製剤に
ついて説明したが、本発明は、これらに限定されるもの
ではなく、ビタミンＡ類可溶化製剤に必要に応じて、電
解質成分や添加剤としてｐＨ調節剤、各種バッファー溶
液、着色防止剤等を添加してもよい。Although the vitamin A-solubilized preparation of the present invention has been described above, the present invention is not limited to these. If necessary, the vitamin A-solubilized preparation may be used as an electrolyte component or an additive. A pH adjuster, various buffer solutions, a coloring inhibitor and the like may be added.
【００５１】[0051]
【実施例】次に、本発明の具体的実施例について説明す
る。Next, specific examples of the present invention will be described.
【００５２】１．ビタミンＡ類可溶化製剤調製例１ （実施例１）1. Preparation Example 1 of Solubilized Vitamin A Soluble Preparation (Example 1)
【００５３】下記の組成からなる各水相と油相とを混合
し、ビタミンＡ類可溶化製剤を調製した。Each aqueous phase having the following composition and an oil phase were mixed to prepare a vitamin A solubilized preparation.
【００５４】水相 プロピレングリコール：４００ｇ メタリン酸ナトリウム（安定化剤）：５ｇ 精製水：３９５ｇAqueous phase Propylene glycol: 400 g Sodium metaphosphate (stabilizer): 5 g Purified water: 395 g
【００５５】油相 ビタミンＡアセテート：５０ｇ ポリオキシエチレン硬化ヒマシ油６０（界面活性剤）：
１５０ｇOil phase Vitamin A acetate: 50 g Polyoxyethylene hydrogenated castor oil 60 (surfactant):
150g
【００５６】まず、容量２Ｌのステンレス製ビーカー
に、プロピレングリコールと、メタリン酸ナトリウムを
精製水に溶解した水溶液とを混合し水相を調製した。First, propylene glycol and an aqueous solution of sodium metaphosphate dissolved in purified water were mixed in a stainless steel beaker having a capacity of 2 L to prepare an aqueous phase.
【００５７】これとは別に、ポリオキシエチレン硬化ヒ
マシ油６０と、ビタミンＡアセテートとを混合し油相を
調製した。Separately, polyoxyethylene hydrogenated castor oil 60 and vitamin A acetate were mixed to prepare an oil phase.
【００５８】先の水相に油相を徐々に加えて混合し粗乳
化させた後、さらに精製水を加えて全量を１Ｌとした。After the oil phase was gradually added to the water phase and mixed and coarsely emulsified, purified water was further added to make a total volume of 1 L.
【００５９】次いで、マイクロフルイダイザーを用い
て、均質化圧１５００kg／cm2 、パス回数１０回で均質
化処理を行い、均質なビタミンＡ類可溶化製剤を調製し
た。ビタミンＡ類可溶化製剤の組成を表１に示す。Next, using a microfluidizer, homogenization treatment was performed at a homogenization pressure of 1500 kg / cm 2 and 10 passes to prepare a homogeneous vitamin A-type solubilized preparation. Table 1 shows the composition of the vitamin A solubilized preparation.
【００６０】[0060]
【表１】 [Table 1]
【００６１】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は２８nmであった。ビタミ
ンＡ類の平均粒径は光散乱法により測定した。Immediately after the preparation, the average particle size of vitamin A in the solubilized preparation of vitamin A was 28 nm. The average particle size of vitamins A was measured by a light scattering method.
【００６２】（実施例２）下記の組成からなる各水相と
油相とを混合し、ビタミンＡ類可溶化製剤を調整した。(Example 2) Each aqueous phase having the following composition and an oil phase were mixed to prepare a vitamin A-solubilized preparation.
【００６３】水相 酒石酸(安定化剤)：１ｇ 精製水：１５００ｇAqueous phase Tartaric acid (stabilizer): 1 g Purified water: 1500 g
【００６４】油相 ビタミンＡパルミテート：１ｇ ポリソルベート８０(界面活性剤)：１６１．１５ｇ ＢＨＴ（酸化防止剤）：０．２４ｇ コレカルシフェロール（ビタミンＤ剤）：０．０１ｇ 酢酸トコフェロール（ビタミンＥ剤）：３６ｇ フィトナジオン（ビタミンＫ剤）：１．６ｇOil phase Vitamin A palmitate: 1 g Polysorbate 80 (surfactant): 161.15 g BHT (antioxidant): 0.24 g Cholecalciferol (vitamin D preparation): 0.01 g Tocopherol acetate (vitamin E preparation) : 36 g phytonadione (vitamin K preparation): 1.6 g
【００６５】まず、容量５００mlのガラス製ビーカー
に、油相の各構成材料を入れ、マグネチックスターラー
を用いて撹拌した。First, each constituent material of the oil phase was placed in a glass beaker having a capacity of 500 ml, and stirred with a magnetic stirrer.
【００６６】これとは別に、容量３Ｌのステンレス製ビ
ーカーに、酒石酸と注射用水とを加え完全に溶解した。Separately, tartaric acid and water for injection were added to a 3 L stainless steel beaker and completely dissolved.
【００６７】次に、酒石酸溶液を攪拌しながら、先に調
製した油相を徐々に添加していき、透明な混合液を得
た。この混合液にさらに注射用水を加えて全量を２Ｌと
し、ビタミンＡ可溶化製剤を調製した。Next, while stirring the tartaric acid solution, the oil phase prepared above was gradually added to obtain a transparent mixed solution. Water for injection was further added to this mixture to make the total volume 2 L, and a vitamin A solubilized preparation was prepared.
【００６８】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は１５nmであった。Immediately after the preparation, the average particle size of vitamin A in the solubilized preparation of vitamin A was 15 nm.
【００６９】（実施例３）ポリソルベート８０(界面活
性剤)の添加量を１６１．３９ｇとし、ＢＨＴを添加し
ないこととした以外は実施例２と同様にしてビタミンＡ
可溶化製剤を調製した。Example 3 Vitamin A was prepared in the same manner as in Example 2 except that the amount of polysorbate 80 (surfactant) was 161.39 g and BHT was not added.
A solubilized formulation was prepared.
【００７０】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は１６nmであった。Immediately after the preparation, the average particle size of vitamin A in the vitamin A-solubilized preparation was 16 nm.
【００７１】（実施例４）下記の組成からなる各水相と
油相とを混合し、ビタミンＡ類可溶化製剤を調製した。Example 4 Each aqueous phase and oil phase having the following composition was mixed to prepare a vitamin A solubilized preparation.
【００７２】水相 クエン酸ナトリウム(安定化剤)：１０ｇ グリセリン：２００ｇ 精製水：１５００ｇAqueous phase Sodium citrate (stabilizer): 10 g Glycerin: 200 g Purified water: 1500 g
【００７３】油相 ビタミンＡ：３ｇ ポリオキシエチレン硬化ヒマシ油６０（界面活性剤）：
２０ｇ 酢酸トコフェロール（ビタミンＥ剤）：３．２ｇ フィトナジオン（ビタミンＫ剤）：０．０５ｇ 大豆油：７４０ｇOil phase Vitamin A: 3 g Polyoxyethylene hydrogenated castor oil 60 (surfactant):
20 g tocopherol acetate (vitamin E): 3.2 g phytonadione (vitamin K): 0.05 g soybean oil: 740 g
【００７４】容量２Ｌのステンレス製ビーカーにグリセ
リンと、クエン酸ナトリウムを精製水に溶解した溶液と
を混合し、水相を調製した。これとは別に、上記油相の
構成材料を混合し油相を調製した。Glycerin and a solution of sodium citrate dissolved in purified water were mixed in a 2 L stainless steel beaker to prepare an aqueous phase. Separately, the constituent materials of the oil phase were mixed to prepare an oil phase.
【００７５】先の水相に油相を徐々に加えて混合し粗乳
化させた後、精製水を加えて全量を２Ｌとした。The oil phase was gradually added to the above aqueous phase, mixed and coarsely emulsified, and purified water was added to make the total volume 2 L.
【００７６】これを、高圧ホモジナイザーを用いて均質
化圧５００kg／cm2 、パス回数５回で均質化処理し、均
質なビタミンＡ類可溶化製剤を調製した。This was homogenized using a high-pressure homogenizer at a homogenizing pressure of 500 kg / cm 2 and five passes to prepare a homogeneous vitamin A-type solubilized preparation.
【００７７】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は４５nmであった。Immediately after the preparation, the average particle size of vitamin A in the vitamin A-solubilized preparation was 45 nm.
【００７８】（比較例１）水相として、メタリン酸ナト
リウム（安定化剤）を含有しない精製水４００ｇを用い
た以外は実施例１と同様にしてビタミンＡ類可溶化製剤
を調製した。Comparative Example 1 A vitamin A solubilized preparation was prepared in the same manner as in Example 1 except that 400 g of purified water containing no sodium metaphosphate (stabilizer) was used as the aqueous phase.
【００７９】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は２８nmであった。The average particle size of vitamin A in the solubilized preparation of vitamin A immediately after preparation was 28 nm.
【００８０】（比較例２）メタリン酸ナトリウム（安定
化剤）の代わりに同量のアスコルビン酸ナトリウム（酸
化防止剤）を用いた以外は実施例１と同様にしてビタミ
ンＡ可溶化製剤を調製した。Comparative Example 2 A vitamin A solubilized preparation was prepared in the same manner as in Example 1 except that the same amount of sodium ascorbate (antioxidant) was used instead of sodium metaphosphate (stabilizer). .
【００８１】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は３２nmであった。Immediately after the preparation, the average particle size of vitamin A in the solubilized preparation of vitamin A was 32 nm.
【００８２】（比較例３）酒石酸（安定化剤）の代わり
にアスコルビン酸（酸化防止剤）を用いた以外は実施例
２と同様にしてビタミンＡ類可溶化製剤を調製した。Comparative Example 3 A solubilized preparation of vitamin A was prepared in the same manner as in Example 2 except that ascorbic acid (an antioxidant) was used instead of tartaric acid (a stabilizer).
【００８３】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は１５nmであった。Immediately after the preparation, the average particle size of vitamin A in the vitamin A-solubilized preparation was 15 nm.
【００８４】（比較例４）クエン酸ナトリウム（安定化
剤）を２０ｇ、グリセリンを１９０ｇ使用して水相を調
製した以外は実施例４と同様にしてビタミンＡ類可溶化
製剤を調製した。Comparative Example 4 A vitamin A-solubilised preparation was prepared in the same manner as in Example 4 except that an aqueous phase was prepared using 20 g of sodium citrate (stabilizer) and 190 g of glycerin.
【００８５】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は１３４nmであった。Immediately after preparation, the average particle size of vitamin A in the vitamin A-solubilized preparation was 134 nm.
【００８６】（比較例５）クエン酸ナトリウム（安定化
剤）を使用せず、水相をグリセリン（２１０ｇ）のみと
した以外は実施例４と同様にしてビタミンＡ類可溶化製
剤を調製した。Comparative Example 5 A solubilized preparation of vitamin A was prepared in the same manner as in Example 4 except that sodium citrate (stabilizer) was not used and the aqueous phase was glycerin (210 g) only.
【００８７】調製直後におけるビタミンＡ類可溶化製剤
中のビタミンＡ類の平均粒径は４６nmであった。The average particle size of vitamin A in the solubilized preparation of vitamin A immediately after preparation was 46 nm.
【００８８】２．ビタミンＡ類の安定性試験 上記各実施例１〜４および比較例１〜５で調製したビタ
ミンＡ可溶化製剤の一部（４００ml）を採り、容量４０
０mlの可塑性素材容器（商品名「テルパック」テルモ
（株）製）に充填し密封した後、１１０℃で１０分間加
熱滅菌した。2. Vitamin A stability test A part (400 ml) of the vitamin A solubilized preparation prepared in each of Examples 1 to 4 and Comparative Examples 1 to 5 above was taken and the volume was 40
After filling and sealing in a 0 ml plastic material container (trade name "Terpac" manufactured by Terumo Corporation), it was heat-sterilized at 110 ° C for 10 minutes.
【００８９】その後４０℃で２ヶ月間保存した後、およ
び２５℃で６ヶ月間保存した後、各ビタミンＡ可溶化製
剤中のビタミンＡ類の平均粒径を調べた。さらに、ビタ
ミンＡ類の含有量を測定し、調製直後のビタミンＡ類の
含有量（１００％）に対する割合を求めた。これらの結
果を表２に示す。After storage at 40 ° C. for 2 months and at 25 ° C. for 6 months, the average particle size of vitamin A in each vitamin A solubilized preparation was examined. Furthermore, the content of vitamin A was measured, and the ratio to the content (100%) of vitamin A immediately after preparation was determined. Table 2 shows the results.
【００９０】[0090]
【表２】 [Table 2]
【００９１】３．ビタミンＡ類可溶化製剤調製例２：経
腸栄養剤の調製 （実施例５）3. Preparation Example 2 of Solubilized Vitamin A Soluble Preparation: Preparation of Enteral Nutrition (Example 5)
【００９２】実施例４のビタミンＡ可溶化製剤を、表３
に示す組成の材料に配合し経腸栄養剤を調製した。The vitamin A solubilized preparation of Example 4 is shown in Table 3.
Was mixed with a material having the composition shown in Table 1 to prepare an enteral nutritional supplement.
【００９３】（比較例６）比較例４のビタミンＡ類可溶
化製剤を用い、試験例１と同様にして経腸栄養剤を調製
した。Comparative Example 6 An enteral nutrition was prepared in the same manner as in Test Example 1 using the vitamin A-solubilized preparation of Comparative Example 4.
【００９４】（比較例７）比較例５のビタミンＡ可溶化
製剤を用い、試験例１と同様にして経腸栄養剤を調製し
た。Comparative Example 7 An enteral nutrition was prepared in the same manner as in Test Example 1 using the vitamin A solubilized preparation of Comparative Example 5.
【００９５】[0095]
【表３】 [Table 3]
【００９６】４．経腸栄養剤中におけるビタミンＡ類の
安定性 実施例５および比較例６，７で調製した各経腸栄養剤を
可塑性素材容器（商品名「テルパック」テルモ（株）
製）に充填し密封した後、１１０℃で１０分間加熱滅菌
し、室温（２５℃）で６ヶ月間保存した後、経腸栄養剤
中のビタミンＡ類の平均粒径および含有量を測定し、調
製直後のビタミンＡ類の含有量（１００％）に対する割
合を求めた。結果を表４に示す。4. Stability of Vitamin A in Enteral Nutrition Each enteral nutrient prepared in Example 5 and Comparative Examples 6 and 7 is made of a plastic material container (trade name “Terpac” Terumo Corporation)
After sealing for 10 minutes at 110 ° C. and storing at room temperature (25 ° C.) for 6 months, the average particle size and content of vitamin A in the enteral nutritional product were measured. The ratio to the content of vitamin A immediately after preparation (100%) was determined. Table 4 shows the results.
【００９７】[0097]
【表４】 [Table 4]
【００９８】これらの結果から、実施例１〜４のビタミ
ンＡ類可溶化製剤は、水溶液中においてもビタミンＡ類
は殆ど損なわれることがなく、活性を維持するものであ
った。また、平均粒径の経時変化が殆どみられないこと
から可溶化状態を長期間安定に保持することがわかっ
た。From these results, it was found that the vitamin A-solubilized preparations of Examples 1 to 4 hardly lost vitamin A even in an aqueous solution and maintained the activity. In addition, it was found that the solubilized state was stably maintained for a long period of time because almost no change in the average particle diameter with time was observed.
【００９９】さらに、このようなビタミンＡ類可溶化製
剤は、経腸栄養剤に添加してもビタミンＡ類が分解等す
ることなく、相分離も生じないで長期にわたり安定に性
状を保つことがわかった。Furthermore, such a solubilized vitamin A preparation can maintain its properties stably for a long period of time without decomposing the vitamin A even when added to an enteral nutritional supplement and without causing phase separation. all right.
【０１００】これに対し、比較例１〜５のビタミンＡ類
可溶化製剤は、いずれも調製直後のビタミンＡ類を９０
％以上維持することはできなかった。また、ビタミンＡ
類の平均粒径も時間の経過とともに増大し、可溶化状態
が安定に維持されなかった。また、比較例４では調製直
後からビタミンＡ類が良好に可溶化せず、時間が経過す
ると相分離を生じた。したがって、このようなビタミン
Ａ類可溶化製剤を経腸栄養剤に配合した場合もビタミン
Ａ類の劣化が著しく、相分離を生じた。On the other hand, the vitamin A-solubilized preparations of Comparative Examples 1 to 5 all contained 90% of vitamin A immediately after preparation.
% Could not be maintained. Vitamin A
The average particle size of the compounds also increased over time, and the solubilized state was not stably maintained. In Comparative Example 4, the vitamin A was not solubilized satisfactorily immediately after the preparation, and phase separation occurred after a lapse of time. Therefore, even when such a vitamin A-solubilized preparation was added to an enteral nutritional supplement, vitamin A was significantly deteriorated and phase separation occurred.
【０１０１】なお、実施例１〜３のビタミンＡ類可溶化
製剤を経腸栄養剤として配合し、実施例５と同様の試験
を行ったが、いずれも良好な結果が得られた。Incidentally, the vitamin A-solubilized preparations of Examples 1 to 3 were blended as an enteral nutrient, and the same test as in Example 5 was carried out. In all cases, good results were obtained.
【０１０２】[0102]
【発明の効果】以上述べたように、本発明のビタミンＡ
類可溶化製剤は、水溶液中においてもビタミンＡ類の分
離、変質、劣化等を生じることがなく、長期間高い安定
性を維持することができる。As described above, the vitamin A of the present invention
The solubilized preparation can maintain high stability for a long time without causing separation, deterioration, deterioration, etc. of vitamin A even in an aqueous solution.
【０１０３】さらに、経腸栄養剤等の各種医薬品製剤、
栄養剤、食品等に配合してもビタミンＡ類の安定性に影
響を及ぼすことなく、品質安定性、保存性に優れた各種
医薬品製剤等を提供することができる。Furthermore, various pharmaceutical preparations such as enteral nutritional supplements,
Various pharmaceutical preparations and the like having excellent quality stability and storage stability can be provided without affecting the stability of vitamin A even when blended in nutrients, foods and the like.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 田村 太作 神奈川県足柄上郡中井町井ノ口1500番地 テルモ株式会社内 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Taisaku Tamura 1500 Inoguchi, Nakai-machi, Ashigara-gun, Kanagawa Prefecture Terumo Corporation
Claims (9)
と、 前記ビタミンＡ類を水溶液に可溶化させる界面活性剤
と、 前記ビタミンＡ類を前記水溶液中で安定に存在させる安
定化剤とを含有するビタミンＡ類可溶化製剤であって、 前記水溶液における前記ビタミンＡ類の平均粒径が５０
nm以下であることを特徴とするビタミンＡ類可溶化製
剤。1. A composition comprising: vitamin A having vitamin A activity; a surfactant for solubilizing the vitamin A in an aqueous solution; and a stabilizer for stably presenting the vitamin A in the aqueous solution. A vitamin A-solubilized preparation, wherein the average particle size of the vitamin A in the aqueous solution is 50.
A solubilized preparation of vitamin A, which is not more than nm.
７ W/V％である請求項１に記載のビタミンＡ類可溶化製
剤。2. The content of the vitamin A is from 0.01 to 2.
The vitamin A class solubilized preparation according to claim 1, which is 7 W / V%.
オキシカルボン酸塩のうち少なくとも１つである請求項
１または２に記載のビタミンＡ類可溶化製剤。3. The vitamin A solubilized preparation according to claim 1, wherein the stabilizer is at least one of oxycarboxylic acid and oxycarboxylic acid salt.
酒石酸のうち少なくとも１つである請求項３に記載のビ
タミンＡ類可溶化製剤。4. The vitamin A solubilized preparation according to claim 3, wherein the oxycarboxylic acid is at least one of citric acid and tartaric acid.
ン酸塩のうち少なくとも１つである請求項１ないし４の
いずれかに記載のビタミンＡ類可溶化製剤。5. The solubilized vitamin A preparation according to claim 1, wherein the stabilizer is at least one of polyphosphoric acid and polyphosphate.
リン酸のうち少なくとも１つである請求項５に記載のビ
タミンＡ類可溶化製剤。6. The vitamin A-solubilised preparation according to claim 5, wherein the polyphosphate is at least one of metaphosphate and pyrophosphate.
７ W/V％である請求項１ないし６のいずれかに記載のビ
タミンＡ類可溶化製剤。7. The method according to claim 1, wherein the content of the stabilizer is 0.02 to 0.1.
The vitamin A solubilized preparation according to any one of claims 1 to 6, which is 7 W / V%.
ポリキシエチレン硬化ヒマシ油６０のうち少なくとも１
つである請求項７に記載のビタミンＡ類可溶化製剤。8. The emulsifier comprises at least one of polysorbate 80 and polyoxyethylene hydrogenated castor oil 60.
The vitamin A-solubilized preparation according to claim 7, which is a solubilized preparation.
W/V％である請求項１ないし８のいずれかに記載のビタ
ミンＡ類可溶化製剤。9. The content of the surfactant is 0.5 to 20.
The vitamin A-solubilized preparation according to any one of claims 1 to 8, which is W / V%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5623698A JPH11236331A (en) | 1998-02-20 | 1998-02-20 | Vitamin as-solubilized preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5623698A JPH11236331A (en) | 1998-02-20 | 1998-02-20 | Vitamin as-solubilized preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11236331A true JPH11236331A (en) | 1999-08-31 |
Family
ID=13021474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5623698A Pending JPH11236331A (en) | 1998-02-20 | 1998-02-20 | Vitamin as-solubilized preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH11236331A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006241132A (en) * | 2005-02-01 | 2006-09-14 | Maruho Co Ltd | Non-aqueous emulsified composition |
| WO2022034614A1 (en) * | 2020-08-11 | 2022-02-17 | Cipla Limited | Phytonadione compositions |
| JP2023514652A (en) * | 2020-02-11 | 2023-04-06 | アドベント セラピューティクス インコーポレイテッド | Compositions of vitamin A palmitate, methods for their preparation, uses and methods containing them |
| JP2023528404A (en) * | 2020-06-01 | 2023-07-04 | アドベント セラピューティクス インコーポレイテッド | Pharmaceutical compositions containing insoluble active ingredients |
-
1998
- 1998-02-20 JP JP5623698A patent/JPH11236331A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006241132A (en) * | 2005-02-01 | 2006-09-14 | Maruho Co Ltd | Non-aqueous emulsified composition |
| JP2023514652A (en) * | 2020-02-11 | 2023-04-06 | アドベント セラピューティクス インコーポレイテッド | Compositions of vitamin A palmitate, methods for their preparation, uses and methods containing them |
| JP2023528404A (en) * | 2020-06-01 | 2023-07-04 | アドベント セラピューティクス インコーポレイテッド | Pharmaceutical compositions containing insoluble active ingredients |
| WO2022034614A1 (en) * | 2020-08-11 | 2022-02-17 | Cipla Limited | Phytonadione compositions |
| CN116367822A (en) * | 2020-08-11 | 2023-06-30 | 希普拉有限公司 | Phytomenadione Composition |
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