KR20020063650A - Novel polyoxypropylenepolyoxyethylene vitamin E and process for preparation thereof - Google Patents
Novel polyoxypropylenepolyoxyethylene vitamin E and process for preparation thereof Download PDFInfo
- Publication number
- KR20020063650A KR20020063650A KR1020010004180A KR20010004180A KR20020063650A KR 20020063650 A KR20020063650 A KR 20020063650A KR 1020010004180 A KR1020010004180 A KR 1020010004180A KR 20010004180 A KR20010004180 A KR 20010004180A KR 20020063650 A KR20020063650 A KR 20020063650A
- Authority
- KR
- South Korea
- Prior art keywords
- vitamin
- integer
- polyoxypropylene polyoxyethylene
- polyoxyethylene
- poe
- Prior art date
Links
- 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 title claims abstract description 385
- 229930003427 Vitamin E Natural products 0.000 title claims abstract description 169
- 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 title claims abstract description 169
- 229940046009 vitamin E Drugs 0.000 title claims abstract description 169
- 235000019165 vitamin E Nutrition 0.000 title claims abstract description 169
- 239000011709 vitamin E Substances 0.000 title claims abstract description 169
- 238000002360 preparation method Methods 0.000 title abstract description 7
- -1 polyoxypropylene Polymers 0.000 claims abstract description 172
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 112
- 229920001451 polypropylene glycol Polymers 0.000 claims abstract description 107
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims abstract description 47
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims abstract description 44
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 32
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 18
- 235000006708 antioxidants Nutrition 0.000 claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- IKGXIBQEEMLURG-NVPNHPEKSA-N rutin Chemical group O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-NVPNHPEKSA-N 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 14
- 239000004094 surface-active agent Substances 0.000 claims description 14
- 230000015227 regulation of liquid surface tension Effects 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims 3
- 239000004902 Softening Agent Substances 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 17
- 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 abstract description 14
- 238000001727 in vivo Methods 0.000 abstract description 11
- 230000002209 hydrophobic effect Effects 0.000 abstract description 8
- 229930003799 tocopherol Natural products 0.000 abstract description 8
- 239000011732 tocopherol Substances 0.000 abstract description 8
- 235000010384 tocopherol Nutrition 0.000 abstract description 8
- 229960001295 tocopherol Drugs 0.000 abstract description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 6
- 238000012644 addition polymerization Methods 0.000 abstract description 4
- 230000003064 anti-oxidating effect Effects 0.000 abstract description 2
- 230000004071 biological effect Effects 0.000 abstract description 2
- 108010077544 Chromatin Proteins 0.000 abstract 1
- 210000003483 chromatin Anatomy 0.000 abstract 1
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 38
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 28
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
- 230000000052 comparative effect Effects 0.000 description 22
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 18
- 235000020778 linoleic acid Nutrition 0.000 description 18
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 18
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 16
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 16
- 239000007788 liquid Substances 0.000 description 13
- 206010015150 Erythema Diseases 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 231100000321 erythema Toxicity 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000002736 nonionic surfactant Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 9
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 238000004945 emulsification Methods 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 125000001165 hydrophobic group Chemical group 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000019612 pigmentation Effects 0.000 description 6
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 229960000984 tocofersolan Drugs 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 229920005654 Sephadex Polymers 0.000 description 5
- 239000012507 Sephadex™ Substances 0.000 description 5
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 239000003995 emulsifying agent Substances 0.000 description 5
- 239000000693 micelle Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 229910001220 stainless steel Inorganic materials 0.000 description 5
- 239000010935 stainless steel Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 230000000975 bioactive effect Effects 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 4
- 238000005187 foaming Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000002563 ionic surfactant Substances 0.000 description 4
- 239000012263 liquid product Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000000049 pigment Substances 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- 229940042585 tocopherol acetate Drugs 0.000 description 4
- 230000007332 vesicle formation Effects 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 150000003722 vitamin derivatives Chemical class 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 3
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000011968 lewis acid catalyst Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- XRUGBBIQLIVCSI-UHFFFAOYSA-N 2,3,4-trimethylphenol Chemical compound CC1=CC=C(O)C(C)=C1C XRUGBBIQLIVCSI-UHFFFAOYSA-N 0.000 description 1
- GZIFEOYASATJEH-UHFFFAOYSA-N 2,8-dimethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydrochromen-6-ol Chemical compound OC1=CC(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000252095 Congridae Species 0.000 description 1
- IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- OFUHPGMOWVHNPN-QWZFGMNQSA-N [(2r)-2,5,7,8-tetramethyl-2-[(4r,8r)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] (9z,12z)-octadeca-9,12-dienoate Chemical compound O1[C@](C)(CCC[C@H](C)CCC[C@H](C)CCCC(C)C)CCC2=C(C)C(OC(=O)CCCCCCC\C=C/C\C=C/CCCCC)=C(C)C(C)=C21 OFUHPGMOWVHNPN-QWZFGMNQSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 229940099418 d- alpha-tocopherol succinate Drugs 0.000 description 1
- DTPCFIHYWYONMD-UHFFFAOYSA-N decaethylene glycol Polymers OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO DTPCFIHYWYONMD-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000341 effect on erythema Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000007760 free radical scavenging Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000003061 melanogenesis Effects 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 238000010428 oil painting Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000001189 phytyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])([H])[C@@](C([H])([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])[C@@](C([H])([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical class [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000012756 surface treatment agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 150000003712 vitamin E derivatives Chemical class 0.000 description 1
- WGVKWNUPNGFDFJ-DQCZWYHMSA-N β-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C WGVKWNUPNGFDFJ-DQCZWYHMSA-N 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
- C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 신규한 폴리옥시프로필렌폴리옥시에틸렌(POE-POE) 비타민 E 및 그의 제조방법에 관한 것으로 하기 일반식(Ⅰ)으로 표시되는 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 제조에 있어서, 항산화 생리활성 비타민 E의 하이드록시기(OH)에 에틸렌옥사이드기를 부가하지 않거나 또는 1 몰을 부가하여 얻은 폴리옥시에틸렌 비타민 E에 다시 프로필렌옥사이드(n=1∼200몰)를 부가중합시킨 폴리옥시프로필렌폴리옥시에틸렌 비타민 E는 프로필렌옥사이드(PO) 쇄가 토코페롤의 크로만링에 보다 가까워져 비공유 전자대의 비편재화(delocalization)가 향상됨으로서 in vivo 항산화력이 증진되는 효과가 있고 또한 베시클 형성능력이 있으며, 항산화 생리활성 비타민 E의 하이드록시기(OH)에 에틸렌옥사이드(m=0∼150몰)를 부가하여 얻은 폴리옥시에틸렌 비타민 E에 다시 프로필렌옥사이드(n=101∼200몰)를 부가중합시킴으로써 제조한 폴리옥시프로필렌폴리옥시에틸렌은 친수성과 균형 있게 소수성이 강화되어 우수한 유화력과 항산화력을 나타내는 뛰어난 효과가 있다.The present invention relates to a novel polyoxypropylene polyoxyethylene (POE-POE) vitamin E and a method for producing the same. Antioxidant biological activity in the preparation of polyoxypropylene polyoxyethylene vitamin E represented by the following general formula (I) Polyoxypropylene polyoxyethylene which addition-polymerized propylene oxide (n = 1-200 mol) to polyoxyethylene vitamin E which did not add ethylene oxide group to the hydroxyl group (OH) of vitamin E, or added 1 mol. Vitamin E has a propylene oxide (PO) chain closer to the chromatin ring of tocopherol, which improves the delocalization of non-covalent electron bands, thereby enhancing the in vivo anti-oxidation ability and the ability to form vesicles. Polyoxyethylene vitamin E obtained by adding ethylene oxide (m = 0 to 150 mol) to the hydroxyl group (OH) of vitamin E A polyoxypropylene polyoxyethylene produced by addition polymerization of propylene oxide (n = 101~200 mol) has the excellent effect that exhibits good yuhwaryeok and antioxidative ability is enhanced hydrophobic and hydrophilic so balanced.
상기 식중, R1은 -(OCH2CH2)m-, R2는이고; n이 1 ∼ 200의 정수일 때 m은 0 ~ 1의 정수이거나 또는 m이 0 ∼ 150의 정수일 때 n은 101 ~ 200의 정수이고; A는이며, B는 비타민 E의 5-, 7- 또는 8- 위치의 CH3이고 P는 1, 3의 정수이다.Wherein R 1 is-(OCH 2 CH 2 ) m- , R 2 is ego; m is an integer from 0 to 1 when n is an integer from 1 to 200, or n is an integer from 101 to 200 when m is an integer from 0 to 150; A is B is CH 3 at the 5-, 7- or 8- position of vitamin E and P is an integer of 1, 3.
Description
본 발명은 신규한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E 및 그 제조방법에 관한 것이다. 더욱 상세하게는, 본 발명은 항산화력, 계면활성력 및 피부 유연효과가 우수하며 또한 피부에 대한 안전성이 뛰어난 신규한 양친매성 물질인 폴리옥시프로필렌폴리옥시에틸렌 비타민 E 및 그 제조방법에 관한 것이다.The present invention relates to a novel polyoxypropylene polyoxyethylene vitamin E and a method for producing the same. More specifically, the present invention relates to a polyoxypropylene polyoxyethylene vitamin E, a novel amphiphilic substance which is excellent in antioxidant activity, surfactant activity, and skin softening effect and excellent in skin safety, and a method for producing the same.
계면활성제는 일반적으로 수용액에서 계면 또는 표면에 흡착되어 계면장력 또는 표면장력을 현저히 저하시키는 성질을 가진다. 생체내에서 계면활성을 나타내는 지질들은 생체기관 및 조직의 생리활성작용에 관여하고 공업적으로 만든 계면활성제는 의약품, 식품, 화장품 및 그외 산업에 널리 사용되고 있는데 그 기능 및 용도에 따라 분산제, 유화제, 가용화제, 기포제, 소포제, 연마제, 윤활제, 표면처리제 및 습윤제 등의 여러가지로 나눌 수 있다. 계면활성제는 친수성기의 성질에 따라 이온성 계면활성제와 비이온성 계면활성제로 나눌 수 있는데 이온성 계면활성제는 친수성기가 이온을 띄므로서 수용해성을 나타내고 비이온성 계면활성제는 물과의 수소결합에 의하여 수용해성을 나타낸다. 동물류의 생체내부는 이온성 물질이 다량 존재하므로 일반적으로 비이온성 물질이 이온성 물질 보다 생체내 적합성이 더 우수한 것으로 알려져 있다. 따라서 생체관련 제품에는 주로 비이온성의 계면활성제가 많이 사용되고 있다. 대표적인 비이온성의 계면활성제는 친수기로서 이온화하는 원자단을 갖지않는 계면활성제의 일군으로서 친수기가 물에 용해되도록 모두 -OH 기를 가지며 아울러 비교적 친수성은 적지만 분자내에 에스테르(-CO·O-), 산아마이드 (-CO·NH-), 에테르 (-O-) 결합을 가지고 있다. 비이온성 계면활성제로서는 폴리에틸렌글리콜 축합형의 제품이 가장 널리 이용되고 있고 또 중요하다. 예를 들면 지방산폴리에틸렌글리콜 축합물 (Niosol, Myrj), 지방산아마이드폴리에틸렌글리콜 축합물, 지방족알콜폴리에틸렌글리콜 축합물 (Leonil, Peregal C), 지방족아민폴리에틸렌글리콜 축합물, 지방족메르캅탄폴리에틸렌글리콜 축합물 (Nyon 218), 알킬페놀폴리에틸렌글리콜 축합물 (Igepal) 및 폴리프로필렌글리콜폴리에틸렌글리콜 축합물 (Pluronics) 등이 있다. 최근에는 이것들 외에 구조가 복잡한 여러 종류의 계면활성제가 개발되어 이용되므로서 비이온계면활성제의 중요성을 더해가고 있다.Surfactants are generally adsorbed on the interface or surface in an aqueous solution to have a property of significantly lowering the interfacial tension or surface tension. Lipids exhibiting surfactant activity in vivo are involved in the biological activity of organs and tissues, and industrially made surfactants are widely used in medicine, food, cosmetics and other industries, depending on their function and use. It can be divided into various agents such as an agent, a foaming agent, an antifoaming agent, an abrasive, a lubricant, a surface treatment agent, and a humectant. Surfactants can be divided into ionic surfactants and nonionic surfactants according to the nature of the hydrophilic group. The ionic surfactants are water-soluble because the hydrophilic groups have ions, and the nonionic surfactants are formed by hydrogen bonding with water. It shows solubility. In vivo in animals, since a large amount of ionic substances are present, it is generally known that nonionic substances have better in vivo compatibility than ionic substances. Therefore, many nonionic surfactants are mainly used in bio-related products. Representative nonionic surfactants are a group of surfactants that do not have an ion group as ionized hydrophilic groups, all of which have -OH groups so that the hydrophilic groups are dissolved in water, and relatively less hydrophilic, but esters (-CO, O-), acidamide in the molecule (-CO.NH-) and ether (-O-) bonds. As the nonionic surfactant, a polyethylene glycol condensation type product is most widely used and important. For example fatty acid polyethylene glycol condensates (Niosol, Myrj), fatty acid amide polyethylene glycol condensates, aliphatic alcohol polyethylene glycol condensates (Leonil, Peregal C), aliphatic amine polyethylene glycol condensates, aliphatic mercaptan polyethylene glycol condensates (Nyon 218), alkylphenol polyethylene glycol condensates (Igepal) and polypropylene glycol polyethylene glycol condensates (Pluronics) and the like. Recently, various types of surfactants having a complicated structure have been developed and used, and the importance of nonionic surfactants has been added.
일반적으로 이온성 및 비이온성 계면활성제는 모두 미셀이라는 분자 또는 이온의 집합체를 만드는 것으로 알려져 있다. 그러나, 왜 이러한 미셀을 만드는가 하는 점은 이온성 계면활성제와 비이온성 계면활성제의 사이에는 여러가지 차이가 있다. 미셀을 만드는 성질은 계면활성제가 갖는 하나의 중요한 성질로서 계면활성제의 구조가 크게 영향을 미치는 것으로 알려져 있으며 수많은 종류의 계면활성제가 용도에 맞게 개발되어 실제 활용되고 있다. 비이온성 계면활성제가 수용액중에서 미셀을 만드는 것은 표면장력, 광산란, 색소와의 상호작용과 그 밖의 연구들로서 밝힐 수 있다. 비이온성 계면활성제가 미셀을 생성하는 원인은 분자중의 알킬쇄가 물의 응집력에 의하여 어떤 농도로 되면 수상에서 빠져나가게 되는 성질, 즉 기본적인 양친매성 구조에 그 원인이 있는 것으로 알려져 있다.In general, both ionic and nonionic surfactants are known to make molecules or aggregates of ions called micelles. However, there are many differences between ionic and nonionic surfactants in making such micelles. The ability to make micelles is one of the important properties of surfactants, and it is known that the structure of surfactants greatly affects them, and numerous types of surfactants have been developed and used for practical purposes. The formation of micelles in aqueous solutions by nonionic surfactants can be identified as surface tension, light scattering, interaction with pigments and other studies. Nonionic surfactants are known to cause micelles due to the nature of the alkyl chain in the molecule being released from the aqueous phase at a certain concentration due to the cohesion of water, that is, the basic amphipathic structure.
본 발명자들은 비이온성 계면활성제의 이러한 특징과 이 양친매성 구조의 특성에 결정적으로 영향을 미치는 것은 역시 소수성 알킬기의 구조임을 알아내고 이러한 특징적인 알킬기 구조에 대한 집중적인 연구로 생체내의 규칙적인 치밀한 지질 2중층 (bilayers) 세포막에 잘 삽입되어 생체막을 산화로부터 잘 보호해주는 비타민 E가 계면활성제의 소수성기로 사용되었을 때 우수한 소수성기로서의 역할을잘 할 수 있으리라 생각하고 비타민 E에 에틸렌옥사이드를 부가하여 계면활성작용, 피부유연 및 보습작용이 우수하며 유해한 활성산소로부터 생체세포를 보호하는 효과가 있는 폴리옥시에틸렌 비타민 E를 발명하여 특허출원 하였다(대한민국 특허 제 083024호, U.S. Patent No. 5,235,073, JP 평성4년 특허원 제 10362호). 그러나 예상과 같이 폴리옥시에틸렌 비타민 E는 그 구조적 특징으로 계면에 아주 잘 흡착되므로서 우수한 계면활성을 나타내기는 하였지만 어떤 종류의 계면활성제에서는 피부에 대한 안전성이 개선되어야 할 필요가 있었다. 즉 소수성 부분의 평평하고 단단한 크로만링 (chromane ring) 부분이 차곡차곡 잘 쌓여지고 끝부분의 피틸 (phytyl)기가 비교적 적은 단면적을 가지면서 유동성을 아울러 가지므로 생체세포막의 2중층에 잘 삽입되어 안전성에 문제를 발생시키는 것으로 생각되었다. 이 안전성 문제는 계면활성제중의 에틸렌옥사이드 쇄의 길이를 조정하여 즉 폴리에틸렌옥사이드 쇄의 길이를 길게 함으로서 해결할 수 있었지만 이때는 친수성이 너무 커져 원하는 계면활성제로서의 기능이 저하되므로 다른 개선방안을 강구하게 되었다. 본 발명자들은 먼저 비타민 E에 에틸렌옥사이드(E.O)를 부가 중합반응 시켜 폴리옥시에틸렌 비타민 E를 얻고, 상기 폴리옥시에틸렌 비타민 E에 다시 프로필렌옥사이드를 부가 중합반응 시켜 비타민 E가 적당한 길이의 폴리옥시에틸렌 쇄와 폴리옥시프로필렌 쇄를 갖게함으로서 소수성기대 친수성기의 크기비가 적절하여 계면활성력이 우수하고 피부에 대한 안전성이 향상된 항산화성을 갖는 새로운 비이온성 양친매성 물질인 폴리옥시프로필렌폴리옥시에틸렌 비타민 E를 발명하였다. (출원번호 98-20705호)The inventors have found that it is also the structure of the hydrophobic alkyl group that decisively affects these characteristics of the nonionic surfactant and the properties of the amphiphilic structure, and the intensive study of these characteristic alkyl group structures results in regular dense lipids in vivo. It is thought that vitamin E, which is well inserted into bilayer cell membranes and protects the biofilm from oxidation, can serve as an excellent hydrophobic group when used as a hydrophobic group of a surfactant. Invented and patented polyoxyethylene vitamin E which has excellent skin softening and moisturizing effect and protects living cells from harmful free radicals (Korean Patent No. 083024, US Patent No. 5,235,073, JP No. 10362). As expected, however, polyoxyethylene vitamin E was very well adsorbed to the interface due to its structural characteristics, but showed good surface activity. However, some types of surfactants needed to improve skin safety. In other words, the flat and hard chromane ring part of the hydrophobic part is piled up well, and the phytyl group at the end has a relatively small cross-sectional area and has fluidity. Was thought to cause problems. This safety problem could be solved by adjusting the length of the ethylene oxide chain in the surfactant, that is, by lengthening the length of the polyethylene oxide chain. However, at this time, the hydrophilicity is so large that the function as the desired surfactant is deteriorated. The present inventors first polymerize ethylene oxide (EO) to vitamin E to obtain polyoxyethylene vitamin E, and further polymerize propylene oxide to polyoxyethylene vitamin E again to form vitamin E in a polyoxyethylene chain of suitable length. Invented polyoxypropylene polyoxyethylene vitamin E, a new nonionic amphiphilic substance having antioxidant capacity with excellent hydrophobicity and improved skin safety due to proper size ratio of hydrophobic group to hydrophilic group by having polyoxypropylene chain . (Application No. 98-20705)
그러나 상기 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 경우 그 구조적 특징으로 우수한 액정생성력을 갖고 베시클을 형성하는 등 우수한 계면활성을 가지며 아울러 항산화력을 나타내지만, 비타민 E에 에틸렌옥사이드(E.O)가 많이 부가되면 될수록 수용해성이 증가되고 항산화력은 감소함으로 인하여 생체내 항산화제인 비타민 E 토코페롤에 비해 항산화력이 약한 결점이 있으므로 개선이 요구되었다. 본 발명자들은 계속적인 연구에서 토코페롤에 에틸렌옥사이드(E.O)가 부가중합 되지 않거나(m=0의 경우) 또는 1몰만 부가되어도(m=1) 프로필렌옥사이드(P.O)의 몰수가 2, 5, 10 등의 폴리옥시프로필렌폴리옥시에틸렌 비타민 E가 적당한 용매조건에서 베시클을 형성하는 등 우수한 계면활성을 나타냄을 밝혀냈고, 비타민 E에 E.O가 부가중합 되지 않고 P.O만 부가중합 될 때 P.O 의 몰수가 약 15이상으로 많아지면 물에 대한 용해도가 점점 감소하면서 우수한 에몰리엔트 특성을 나타내는 것을 알 수 있었다.However, in the case of the polyoxypropylene polyoxyethylene vitamin E, its structural characteristics have excellent liquid crystal production and form a vesicle and have excellent surface activity and antioxidant properties, but ethylene oxide (EO) is added to vitamin E in a large amount. As the water solubility increases and the antioxidant power decreases, the antioxidant capacity is weaker than that of the vitamin E tocopherol, which is in vivo. In an ongoing study, the inventors have found that the number of moles of propylene oxide (PO) is 2, 5, 10, etc., even if ethylene oxide (EO) is not polymerized (to m = 0) or only 1 mole is added to tocopherol (m = 1). Polyoxypropylene polyoxyethylene vitamin E showed excellent surface activity such as vesicle formation under suitable solvent conditions. When mole number of PO is added when only EO is added to vitamin E without addition polymerization, It was found that the higher the solubility in water, the lower the solubility in water and the better emollient properties.
또한, 본 발명자들의 선출원한 폴리옥시프로필렌폴리옥시에틸렌(POP-POE) 비타민 E의 폴리옥시프로필렌(POP)은 폴리옥시에틸렌(POE)이 비교적 작을 때는 문제가 없으나 POE가 비교적 큰 150 E.O 부근에서는 POP의 구조내에 함유된 P.O 내 산소원자(O) 때문에 (개개의 P.O가 강한 소수성을 갖지 못함) POP가 비교적 큰 100 P.O에서도 소수성이 충분하지 못하여 우수한 유화제로서의 기능이 부족하였다. 따라서 우수한 유화력을 나타내기 위해서는 그 소수성의 향상이 요망되는데 이는 Davis J. T.(Proc. 2nd. Int. Congr. Surface activity, London 1, 426, 1957)가 제안한 친수성-소수성 균형 그룹 수[hydrophilic-lipophilic balance (HLB) groupnumber : 친수성기는 양(+)의 값을 갖고 소수성기 음(-)값을 갖는다]의 계산식에 의해서 토코페롤은 -8.65 , E.O는 1.3 그리고 P.O는 -0.125의 그룹수 값으로도 설명된다. 그러나 소수성이 너무 크면 계면에서의 배향특성이 방해를 받을 수 있고 또한 항산화력이 감소할 수 있으므로 적당한 소수성기의 길이가 요구되었다. 본 발명자들은 선출원한 특허에서의 부가된 POP 소수성기 길이를 P.O 200 몰까지 증가시키면 폴리옥시프로필렌폴리옥시에틸렌이 적당한 항산화력과 우수한 유화 계면활성력 및 액정 생성력을 나타냄을 알 수 있었다.In addition, the polyoxypropylene polyoxyethylene (POP-POE) of the present inventors of the present invention, polyoxypropylene (POP) of vitamin E has no problem when the polyoxyethylene (POE) is relatively small, but the POP in the vicinity of 150 EO where the POE is relatively large Due to the oxygen atom (O) in PO contained in the structure of the individual PO does not have strong hydrophobicity, even in 100 PO having a relatively large POP, the hydrophobicity was not sufficient, and the function as an excellent emulsifier was insufficient. Therefore, in order to show excellent emulsification, hydrophobicity is required to be improved, which is proposed by Davis JT (Proc. 2nd. Int. Congr. Surface activity, London 1, 426, 1957). HLB) groupnumber: The hydrophilic group has a positive value and the hydrophobic group has a negative value]. Tocopherol is also described as a group number value of -8.65 for EO, 1.3 for EO and -0.125 for PO. However, if the hydrophobicity is too large, proper orientation of the hydrophobic group was required because the orientation property at the interface could be disturbed and the antioxidant power could be reduced. The inventors have found that increasing the length of the added POP hydrophobic group in the patent application to 200 moles of P.O shows that the polyoxypropylenepolyoxyethylene exhibits moderate antioxidant activity, good emulsifying surfactant activity and liquid crystal generation ability.
상기와 같은 사실에 착안하여 본 발명자들은 에틸렌옥사이드의(E.O)의 몰수를 0∼1이 되게 부가하여 폴리옥시프로필렌폴리옥시에틸렌(POP-POE)비타민 E의 소수성기 POP와 친수성기 POE의 크기를 조절하였고 그 결과 소수성이 향상되고 낮은 분자량에서도 선출원한 기존의 폴리옥시프로필렌폴리옥시에틸렌(POP-POE)에 비해 항산화력이 뛰어나고, 우수한 계면활성력이 존재하는 폴리옥시프로필렌폴리옥시에틸렌 비타민 E를 제조하였으며, P.O의 몰수를 101 ∼ 200이 되게 부가하여 친수성과 균형 있게 소수성을 강화시킴으로 우수한 유화력을 나타내는 폴리옥시프로필렌폴리옥시에틸렌 비타민 E 제조함으로써 본 발명을 완성하였다.In view of the above fact, the present inventors adjusted the size of the hydrophobic group POP and the hydrophilic group POE of polyoxypropylene polyoxyethylene (POP-POE) vitamin E by adding the mole number of (EO) of ethylene oxide to 0-1. As a result, polyoxypropylenepolyoxyethylene vitamin E having excellent hydrophobicity and superior antioxidant activity compared to conventional polyoxypropylene polyoxyethylene (POP-POE), which has been applied for at low molecular weight, was prepared. The present invention has been completed by preparing polyoxypropylene polyoxyethylene vitamin E exhibiting excellent emulsification power by adding a mole number of PO to be in the range of 101 to 200 to enhance hydrophobicity in balance with hydrophilicity.
따라서, 본 발명의 목적은 상기와 같은 사실을 감안하여 안출한 것으로 하기 일반식(I)Therefore, the objective of this invention was devised in view of the above fact, and is following General formula (I)
[식중, R1은 -(OCH2CH2)m-, R2는이고; n이 1 ∼ 200의 정수일 때 m은 0 ~ 1의 정수이거나 또는 m이 0 ∼ 150의 정수일 때 n은 101 ~ 200의 정수이고; A는이며; B는 비타민 E의 5-, 7- 또는 8- 위치의 CH3이고 P는 1, 3의 정수이다]로 나타내지는 신규한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E 를 제공함에 있다.[Wherein R 1 is-(OCH 2 CH 2 ) m- , R 2 is ego; m is an integer from 0 to 1 when n is an integer from 1 to 200, or n is an integer from 101 to 200 when m is an integer from 0 to 150; A is Is; B is CH 3 at the 5-, 7- or 8- position of vitamin E and P is an integer of 1, 3].
본 발명의 다른 목적은 하기 일반식 (Ⅱ)로 나타내지는 비타민 E를 하기 일반식(Ⅲ)로 나타내지는 에틸렌옥사이드(EO)와 반응시킨 후 다시 하기 일반식(Ⅳ)로 나타내지는 프로필렌옥사이드(PO)와 반응시켜 하기 일반식(I)의 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 제조방법을 제공함에 있다.Another object of the present invention is to react vitamin E represented by the following general formula (II) with ethylene oxide (EO) represented by the following general formula (III), and then again to propylene oxide (PO) represented by the following general formula (IV) And a method for producing polyoxypropylene polyoxyethylene vitamin E of the following general formula (I).
[상기 식중, R1은 -(OCH2CH2)m-, R2는이고; n이 1 ∼ 200의 정수일 때 m은 0 ~ 1의 정수이거나; 또는 m이 0 ∼ 150의 정수일 때 n은 101 ~ 200의 정수이고; A는이며; B는 비타민 E의 5-, 7- 또는 8- 위치의 CH3이고 P는 1, 3의 정수이다].[Wherein, R 1 is-(OCH 2 CH 2 ) m- , R 2 is ego; when n is an integer from 1 to 200 m is an integer from 0 to 1; Or n is an integer from 101 to 200 when m is an integer from 0 to 150; A is Is; B is CH 3 at the 5-, 7- or 8- position of vitamin E and P is an integer of 1, 3].
본 발명의 또 다른 목적은 신규한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E를 함유하는 피부보호제를 제공함에 있다.Another object of the present invention is to provide a skin protectant containing the novel polyoxypropylenepolyoxyethylene vitamin E.
본 발명의 상기 목적은 밀폐 용기내에서 무수 고압조건으로 염기성 촉매 또는 루이스산계 촉매를 사용하여 합성 비타민 E 또는 천연 비타민 E의 하이드록시기(OH)에 에틸렌옥사이드기를 부가하지 않거나 또는 1몰을 부가하고 얻은(m=0∼1) 폴리옥시에틸렌 비타민 E에 다시 프로필렌옥사이드(n=1∼200)를 부가중합시킨 폴리옥시프로필렌폴리옥시에틸렌 비타민 E를 제조하였으며, 또한 에틸렌옥사이드기를 부가하여 얻은(m=0∼150) 폴리옥시에틸렌 비타민 E에 프로필렌옥사이드101몰 이상에서부터 200몰을 부가중합시킴으로써 분자량이 다른 여러종의 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(즉, n=1∼200일 때 m= 0∼1 이거나 또는 m=0∼150일 때 n=101∼200임)를 제조한 후 상기 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 항산력 및 자외선에 의한 홍발발생과 멜라닌 색소형성에 미치는 영향과 계면활성작용을 조사하므로써 달성하였다.The object of the present invention is not to add ethylene oxide group or 1 mole of hydroxy group (OH) of synthetic vitamin E or natural vitamin E using basic catalyst or Lewis acid catalyst in dry container under anhydrous high pressure condition Polyoxypropylene polyoxyethylene vitamin E was prepared by addition-polymerizing propylene oxide (n = 1 to 200) to the obtained polyoxyethylene vitamin E (m = 0 to 1), and further obtained by adding an ethylene oxide group (m = 0 to 150) Polyoxyethylene vitamin E of polyoxyethylene vitamin E having various molecular weights of different polyoxypropylene polyoxyethylene vitamin E having different molecular weights by addition polymerization from 101 moles or more of propylene oxide to 200 moles (i.e., m = 0 to n = 200) 1 or n = 101 to 200 when m = 0 to 150), and the antioxidative power of the polyoxypropylene polyoxyethylene vitamin E prepared above and the occurrence of red hair due to ultraviolet rays It was achieved by investigating the influence and the surface-active action on melanin formation.
이하, 본 발명의 구성 및 작용을 상세히 설명하고자 한다.Hereinafter, the configuration and operation of the present invention will be described in detail.
도 1은 실시예 1에서 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(1)의1H NMR 스펙트럼이다.1 is a 1 H NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (1) prepared in Example 1. FIG.
도 2는 실시예 3에서 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(3)의1H NMR 스펙트럼이다.2 is a 1 H NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (3) prepared in Example 3. FIG.
도 3은 실시예 1에서 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(1)의 베시클 주사전자현미경 사진이다.Figure 3 is a vesicle scanning electron micrograph of the polyoxypropylene polyoxyethylene vitamin E (1) prepared in Example 1.
본 발명은 촉매인 메톡시나트륨(CH3ONa) 존재하에 합성비타민 E와 프로필렌옥사이드를 반응시켜 실온에서 액상인 폴리옥시프로필렌(POP5-POE0) 비타민 E를 제조하고 분석하는 단계; 촉매인 수산화칼륨(KOH) 존재하에 합성 비타민 E와 프로필렌옥사이드와 반응시켜 실온에서 액상인 폴리옥시프로필렌[POP(2)-POE(0)] 비타민 E를 제조하고 분석하는 단계; 촉매인 수산화칼륨(KOH) 존재하에 천연 비타민 E와 에틸렌옥사이드를 반응시켜 폴리옥시에틸렌 바타민 E를 얻은 후 다시 촉매인 수산화칼륨(KOH) 존재하에 프로필렌옥사이드를 반응시켜 실온에서 액상인 폴리옥시프로필렌폴리옥시에틸렌[POP(10)-POE(1)] 비타민 E를 제조하고 분석하는 단계; 상기와 같은 방법으로 합성 비타민 E, 에틸렌옥사이드, 프로필렌옥사이드 및 촉매인 수산화 나트륨의 양을 달리하며 반응시켜 실온에서 반고상인 폴리옥시프로필렌폴리옥시에틸렌[POP(150)-POE(100), POP(200)-POE(150)] 비타민 E를 제조하고 분석하는 단계;상기 제조한 신규한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E에 리놀산을 첨가하고 시간경과에 따른 과산화물가를 측정하여 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 항산화력을 측정하는 단계; 상기 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E를 인체 피부에 도포하고 자외선 조사하여, 폴리옥시프로필렌폴리옥시에틸렌 비타민 E가 자외선에 의한 홍반발생과 멜라닌 색소형성에 미치는 영향을 조사하는 단계로 구성된다.The present invention comprises the steps of preparing and analyzing a liquid polyoxypropylene (POP5-POE0) vitamin E at room temperature by reacting synthetic vitamin E and propylene oxide in the presence of a catalyst methoxy sodium (CH 3 ONa); Preparing and analyzing liquid polyoxypropylene [POP (2) -POE (0)] vitamin E at room temperature by reacting with synthetic vitamin E and propylene oxide in the presence of a catalyst potassium hydroxide (KOH); Polyoxyethylene Batamine E is obtained by reacting natural vitamin E with ethylene oxide in the presence of potassium hydroxide (KOH) as a catalyst, followed by propylene oxide in the presence of potassium hydroxide (KOH) as a catalyst. Preparing and analyzing oxyethylene [POP (10) -POE (1)] vitamin E; Synthetic vitamin E, ethylene oxide, propylene oxide and the amount of sodium hydroxide as a catalyst are reacted in the same manner as described above to react polyoxypropylene polyoxyethylene [POP (150) -POE (100), POP (200), which is semi-solid at room temperature. ) -POE (150)] preparing and analyzing the vitamin E; polyoxypropylene polyoxyethylene vitamin E by adding linoleic acid to the prepared new polyoxypropylene polyoxyethylene vitamin E and measuring the peroxide value over time Measuring the antioxidant power of the; The polyoxypropylene polyoxyethylene vitamin E prepared above is applied to human skin and irradiated with ultraviolet light, and the effect of polyoxypropylene polyoxyethylene vitamin E on erythema generation and melanin pigmentation caused by ultraviolet rays is investigated.
상기 POP(n)-POE(m)은 부가된 프로필렌옥사이드(평균몰수)-부가된 에틸렌옥사이드(평균몰수)를 나타낸 것이다.The POP (n) -POE (m) represents added propylene oxide (average moles) -added ethylene oxide (average moles).
본 발명의 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 합성에 이용되는 비타민 E는 dl-α 토코페롤, dl-β 토코페롤, dl-γ토코페롤 또는 dl-δ 토코페롤 등의 합성비타민 E 또는 식물의 종자 등에서 추출된 천연 비타민 E 또는 이들의 에스테르일 수 있으며 비타민 E 에스테르로는 비타민 E 아세테이트, 비타민 E 팔미테이트, 비타민 E 석시네이트 및 비타민 E 리놀레이트가 포함된다.Vitamin E used in the synthesis of polyoxypropylene polyoxyethylene vitamin E of the present invention is extracted from synthetic vitamin E, such as dl-α tocopherol, dl-β tocopherol, dl-γ tocopherol or dl-δ tocopherol, or seeds of plants. Natural vitamin E or esters thereof, and vitamin E esters include vitamin E acetate, vitamin E palmitate, vitamin E succinate and vitamin E linoleate.
본 발명의 염기성 촉매로는 CH3ONa, NaOH 또는 KOH 등이 사용되며, 루이스산 촉매로는 BF3또는 SnCl4혹은 SbCl5등이사용되며 비타민 E에 대하여 또는 폴리옥시에틸렌 비타민 E에 대하여 각각 0.02-0.8 중량%의 양으로 사용되나 반응조건에 따라 적당히 가감하여 사용할 수 있다.CH 3 ONa, NaOH or KOH is used as the basic catalyst of the present invention, and BF 3 or SnCl 4 or SbCl 5 is used as the Lewis acid catalyst and 0.02 for vitamin E or for polyoxyethylene vitamin E, respectively. It is used in an amount of -0.8% by weight, but it can be used appropriately depending on the reaction conditions.
본 발명에서 반응 온도는 일반적으로 120-180 ℃, 바람직하게는 145-160 ℃이며, 반응 압력은 일반적으로 1.0-8.0 kg/cm2,바람직하게는 3.5-5.5 kg/cm2이다.이하 본 발명의 구체적인 방법을 실시예를 들어 상세히 설명하고자 하지만 본 발명의 권리범위는 이들 실시예에만 한정되는 것은 아니다.In the present invention, the reaction temperature is generally 120-180 ° C, preferably 145-160 ° C, and the reaction pressure is generally 1.0-8.0 kg / cm2,Preferably 3.5-5.5 kg / cm2Hereinafter, specific examples of the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited to these Examples.
실시예 1: 폴리옥시프로필렌폴리옥시에틸렌[POP(5)-POE(0)] 비타민 E(1) 제조Example 1 Preparation of Polyoxypropylene Polyoxyethylene [POP (5) -POE (0)] Vitamin E (1)
1ℓ의 2중 스테인레스스틸로 된 오토클레이브에 합성비타민 E (dl α-토코페롤) 129.2 g (0.30 mol)을 넣고 다시 고순도의 메톡시나트륨 (CH3ONa) 0.15 g을 넣은 후 70 ℃로 가열하면서 진공도가 약 730 mmHg가 되게하여 약 30 분간 탈수한 다음 프로필렌옥사이드 116g (2.0 mol)을 압입하여 8시간 동안 150-155℃에서 반응시켜 연황색의 액체를 얻었다. 반응을 종결한 후 질소로 3회 배기시켜 미반응 프로필렌옥사이드를 제거하고 반응 혼합물을 약 30 ℃로 냉각한 후 구연산을 미량 가하여 촉매로 가해진 알칼리 성분을 중화하고 클로로포름-메탄올 (1:1)을 용출용매로 한 세파덱스 LH-50 칼럼크로마토그라피로 정제하여 235.6g의 액상 폴리옥시프로필렌 비타민 E(1)를 얻었으며 이 액상 생성물의 분석결과는 하기와 같다.129.2 g (0.30 mol) of synthetic vitamin E (dl α-tocopherol) was added to a 1-liter stainless steel autoclave, and 0.15 g of high-purity methoxy sodium (CH 3 ONa) was added. It was about 730 mmHg and dehydrated for about 30 minutes, and then 116 g (2.0 mol) of propylene oxide was injected and reacted at 150-155 ° C. for 8 hours to obtain a pale yellow liquid. After the completion of the reaction, the reaction mixture was evacuated three times with nitrogen to remove unreacted propylene oxide, the reaction mixture was cooled to about 30 ° C., and a small amount of citric acid was added to neutralize the alkaline component added to the catalyst and eluted chloroform-methanol (1: 1). Purified with Sephadex LH-50 column chromatography using a solvent, 235.6 g of liquid polyoxypropylene vitamin E (1) was obtained. The analysis results of the liquid product are as follows.
분석결과Analysis
(1) 성상 : 실온에서 액상인 연황색의 물질(1) Appearance: Light yellow substance which is liquid at room temperature
(2) 원소분석결과 : C44H79O7분자량 (상대분자량)으로서(2) Elemental analysis result: C 44 H 79 O 7 as molecular weight (relative molecular weight)
계산치(%) : C : 73.44, H : 10.98, N : 0.00Calculated Value (%): C: 73.44, H: 10.98, N: 0.00
실측치(%) : C : 73.21, H : 11.03, N : 0.03Found (%): C: 73.21, H: 11.03, N: 0.03
(3) 반응수율 : 96.1%(3) Yield of reaction: 96.1%
(4) 부가된 에틸렌옥사이드 몰수(평균) : 0 몰(4) Number of moles of added ethylene oxide (average): 0 mol
(5) 부가된 프로필렌옥사이드 몰수(평균) : 5 몰(5) Number of moles of propylene oxide added (average): 5 moles
(6) NMR (핵자기공명) 스펙트럼(6) NMR (nuclear magnetic resonance) spectrum
본 실시예에서 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(1)의1H NMR 스펙트럼은 도 1에 나타낸 바와 같으며 이를 비타민 E의1H NMR 스펙트럼과 비교하였다. 비타민 E의1H NMR 스펙트럼에는 1.17-1.3δ에서 -CH2-CH2- 또는 -CH3피크가 나타나고 2.8δ에서 페닐의 -CH3(3개) 피크가 나타나며 4.1δ에서는 트리메틸페놀의 -OH 피크가 나타나는 반면 도 1의 본 실시예에서 얻은 폴리옥시프로필렌 비타민 E(1)의1H NMR 스펙트럼에서는 4.1δ에서의 -OH 피크가 사라지고 폴리프로필렌옥사이드 -(CH(CH3)-CH2-O)nH 중의 H 피크가 3.5-3.8δ에서 나타났으며, 3.97δ에서 프로필렌옥사이드 말단 -OH의 H 피크가 나타났고, 폴리프로필렌옥사이드 -(CH(CH3)-CH2-O)n- 중 -CH3의 피크가 1.3δ에 더해져 나타났다.The 1 H NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (1) prepared in this example is shown in Figure 1 and compared with the 1 H NMR spectrum of vitamin E. The 1 H NMR spectrum of vitamin E shows -CH 2 -CH 2 -or -CH 3 peak at 1.17-1.3δ, -CH 3 (3) peak of phenyl at 2.8δ and -OH of trimethylphenol at 4.1δ In the 1 H NMR spectrum of the polyoxypropylene vitamin E (1) obtained in this example of FIG. 1 while the peak appeared, the -OH peak at 4.1δ disappeared and the polypropylene oxide-(CH (CH 3 ) -CH 2 -O ) n of H H was a peak is observed in 3.5-3.8δ, got an H peak of the end -OH of propylene oxide appears at 3.97δ, polypropylene oxide - (CH (CH 3) -CH 2 -O) n - in -CH 3 The peak of was added to 1.3δ.
실시예 2: 폴리옥시프로필렌폴리옥시에틸렌 [POP(2)-POE(0)] 비타민 E(2) 제조Example 2 Preparation of Polyoxypropylene Polyoxyethylene [POP (2) -POE (0)] Vitamin E (2)
1ℓ의 2중 스테인레스스틸로 된 오토클레이브에 합성비타민 E (dl α-토코페롤) 220 g (0.51 mol)을 넣고 다시 고순도의 수산화칼륨 0.2 g을 넣고 75 ℃까지 가열하면서 진공도가 약 750 mmHg가 되게하여 약 30 분간 탈수한 다음 프로필렌옥사이드 64g (1.1 mol)을 압입하여 135-145℃ 에서 약 6 시간 동안 교반하면서 반응시켜 황색의 액체를 얻었다. 반응을 종결 후 질소로 2회 배기시켜 미반응 프로필렌옥사이드 및 부생한 1, 4-디옥산을 제거하고 반응혼합물을 약 30 ℃로 냉각한 후 구연산을 미량 가하여 촉매로 가해진 알칼리 성분을 중화하고 미반응 비타민 E는 톨루엔으로 제거한 후 클로로포름-메탄올 (1:1)을 용출용매로한 세파덱스 LH-50 칼럼크로마토그라피로 정제하여 271.5g의 액상 폴리옥시프로필렌 비타민 E(2)를 얻었으며 이 액상 생성물의 분석결과는 하기와 같다.220 g (0.51 mol) of synthetic vitamin E (dl α-tocopherol) was added to an autoclave of 1 L of double stainless steel, and 0.2 g of high purity potassium hydroxide was added thereto, followed by heating to 75 ° C. to obtain a vacuum of about 750 mmHg. After dehydrating for about 30 minutes, 64 g (1.1 mol) of propylene oxide was indented and reacted with stirring at 135-145 ° C. for about 6 hours to obtain a yellow liquid. After completion of the reaction, the reaction product was evacuated twice with nitrogen to remove unreacted propylene oxide and byproduct 1,4-dioxane, the reaction mixture was cooled to about 30 ° C., and a small amount of citric acid was added to neutralize the alkali component added to the catalyst and not react. Vitamin E was removed with toluene and purified by Sephadex LH-50 column chromatography using chloroform-methanol (1: 1) as eluent to obtain 271.5 g of liquid polyoxypropylene vitamin E (2). The analysis results are as follows.
분석결과Analysis
(1) 성상 : 실온에서 액상인 연황색의 물질(1) Appearance: Light yellow substance which is liquid at room temperature
(2) 원소분석결과 : C35H61O4분자량 (상대분자량)으로서(2) Elemental analysis result: As molecular weight (relative molecular weight) C 35 H 61 O 4
계산치(%) : C : 77.06, H : 11.2, N : 0.00Calculated Value (%): C: 77.06, H: 11.2, N: 0.00
실측치(%) : C : 76.87, H : 11.36, N : 0.04Found (%): C: 76.87, H: 11.36, N: 0.04
(3) 반응수율 : 95.0%(3) Yield of reaction: 95.0%
(4) 부가된 에틸렌옥사이드 몰수(평균) : 0 몰(4) Number of moles of added ethylene oxide (average): 0 mol
(5) 부가된 프로필렌옥사이드 몰수(평균) : 2 몰(5) Number of moles of propylene oxide added (average): 2 moles
실시예 3: 폴리옥시프로필렌폴리옥시에틸렌[POP(10)-POE(1)] 비타민 E(3) 제조 2ℓ의 2중 스테인레스스틸로 된 오토클레이브에 합성비타민 E (dl α-토코페롤) 107.7g (0.25 mol)을 넣고 다시 고순도의 수산화칼륨 (99.9%) 0.1 g을 넣고 80℃까지 가열하면서 진공도가 약 750 mmHg가 되게 하여 약 40분간 탈수한 다음 에틸렌옥사이드 13.2g (0.3 mol)을 압입하여 160-165 ℃에서 약 6시간 동안 교반하면서 반응완료시켰다. 반응완료 후 액상의 반응물을 얻고 다시 KOH (99.9%) 0.15 g 존재하에 얻어진 폴리옥시에틸렌 비타민 E를 7 시간 동안 156-160 ℃온도에서 프로필렌옥사이드 174g (3.0 mol)과 반응시켜 미황색의 액체를 얻었다. 반응종결 후 질소로 3회 배기시켜 미반응 에틸렌옥사이드와 프로필렌옥사이드 및 부생한 1, 4-디옥산을 제거한 다음 반응혼합물을 약 30℃로 냉각한 후 구연산을 미량 가하여 촉매로 가해진 알칼리 성분을 중화시켰다. 미반응 비타민 E를 톨루엔으로 제거한 후 클로로포름-메탄올 (1:1)을 용출용매로한 세파덱스 LH-50 칼럼크로마토그라피로 정제하여 283.1g의 액상 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(3)을 얻었으며 이 액상 생성물의 분석결과는 하기와 같다. Example 3 Polyoxypropylene Polyoxyethylene [POP (10) -POE (1)] Preparation of Vitamin E (3 ) 107.7 g of synthetic vitamin E (dl α-tocopherol) in an autoclave of 2 L of double stainless steel ( 0.25 mol), add 0.1 g of high-purity potassium hydroxide (99.9%), and heat to 80 ° C to obtain a vacuum of about 750 mmHg, dehydrate for 40 minutes, and inject 13.2g (0.3 mol) of ethylene oxide into 160- The reaction was completed with stirring at 165 ° C. for about 6 hours. After completion of the reaction, a liquid reaction product was obtained, and then, polyoxyethylene vitamin E obtained in the presence of 0.15 g of KOH (99.9%) was reacted with 174 g (3.0 mol) of propylene oxide at 156-160 ° C. for 7 hours to obtain a pale yellow liquid. After completion of the reaction, the reaction mixture was evacuated three times with nitrogen to remove unreacted ethylene oxide, propylene oxide, and by-product 1,4-dioxane. The reaction mixture was cooled to about 30 ° C., and a small amount of citric acid was added to neutralize the alkaline component added to the catalyst. . Unreacted vitamin E was removed with toluene and purified with Sephadex LH-50 column chromatography using chloroform-methanol (1: 1) as an eluting solvent to obtain 283.1 g of liquid polyoxypropylenepolyoxyethylene vitamin E (3). The analysis results of this liquid product are as follows.
분석결과Analysis
(1) 성상 : 실온에서 액상인 미황색의 물질(1) Appearance: Light yellow substance which is liquid at room temperature
(2) 원소분석결과 : C61H113O23분자량 (상대분자량)으로서(2) Elemental Analysis Result: As C 61 H 113 O 23 Molecular Weight (relative molecular weight)
계산치(%) : C : 60.35, H : 9.32, N : 0.00Calculated Value (%): C: 60.35, H: 9.32, N: 0.00
실측치(%) : C : 60.75, H : 9.10, N : 0.03Found (%): C: 60.75, H: 9.10, N: 0.03
(3) 반응수율 : 96.0%(3) Yield of reaction: 96.0%
(4) 부가된 에틸렌옥사이드 몰수(평균) : 1 몰(4) Number of moles of added ethylene oxide (average): 1 mole
(5) 부가된 프로필렌옥사이드 몰수(평균) : 10 몰(5) Number of moles of propylene oxide added (average): 10 moles
(6) NMR 스펙트럼(6) NMR spectrum
본 실시예에서 얻은 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(3)의1H NMR 스펙트럼은 도 2에 나타낸 바와 같으며 이를 비타민 E의1H NMR 스펙트럼과 비교하였다. 도 2에서 보면 비타민 E에서 보인 4.1δ의 -OH 피크가 사라지고 폴리에틸렌옥사이드 (-CH2-CH2-O)m-의 H 피크와 폴리프로필렌옥사이드 -(CH(CH3)-CH2-O)nH 중의 H 피크가 3.5-3.8δ에서 나타났으며, 3.97δ에서 프로필렌옥사이드 말단의 -OH의 피크가 나타났고 폴리프로필렌옥사이드 -(CH(CH3)-CH2-O)nH 중 -CH3의 피크가 1.3δ에 더해져 나타났다.The 1 H NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (3) obtained in this example is shown in Figure 2 and compared with the 1 H NMR spectrum of vitamin E. In Figure 2, the -OH peak of 4.1δ seen in vitamin E disappears and the H peak of polyethylene oxide (-CH 2 -CH 2 -O) m -and polypropylene oxide-(CH (CH 3 ) -CH 2 -O) n H The H peak of was found at 3.5-3.8δ, the peak of -OH at the end of propylene oxide was found at 3.97δ, and the peak of -CH 3 in polypropylene oxide-(CH (CH 3 ) -CH 2 -O) n H The peak was added to 1.3δ.
실시예 4: 폴리옥시프로필렌폴리옥시에틸렌[POP(150)-POE(100)] 비타민 E(4) 제조Example 4 Preparation of Polyoxypropylene Polyoxyethylene [POP (150) -POE (100)] Vitamin E (4)
2ℓ의 2중 스테인레스스틸로 된 오토클레이브에 합성비타민 E (dl α-토코페롤) 8.61g (0.02 mol)을 넣은 후 다시 고순도의 수산화칼륨(99.9%) 0.2 g을 넣고 75 ℃까지 가열하면서 진공도가 약 750 mmHg가 되게 하여 약 30분간 탈수한 다음 에틸렌옥사이드 101.2g (2.3 mol)을 압입하여 160-165 ℃에서 약 6시간 동안 교반하면서 반응시켰다. 반응완료 후 얻어진 폴리옥시에틸렌 비타민 E를 다시 KOH (99.9%) 0.15 g 존재하에 8 시간 동안 155∼160 ℃온도에서 프로필렌옥사이드 200g (3.45 mol)과 반응시켜 미황색의 고체를 얻었다. 반응종결 후 질소로 3회 배기시켜 미반응 에틸렌옥사이드와 프로필렌옥사이드 및 부생한 1, 4-디옥산을 제거한 다음 반응혼합물을 약 45℃로 냉각한 후 구연산을 미량 가하여 촉매로 가해진 알칼리 성분을 중화시켰다. 미반응 비타민 E를 톨루엔으로 제거한 후 클로로포름-메탄올 (1:1)을 용출용매로한 세파덱스 LH-50 칼럼크로마토그라피로 정제하여 291.2g의 고상 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(4)을 얻었으며 이 액상 생성물의 분석결과는 하기와 같다.Into an autoclave of 2 L of double stainless steel, 8.61 g (0.02 mol) of synthetic vitamin E (dl α-tocopherol) was added, followed by 0.2 g of high-purity potassium hydroxide (99.9%), and heated to 75 ° C., and the degree of vacuum was reduced. After dehydrating for about 30 minutes to 750 mmHg, 101.2 g (2.3 mol) of ethylene oxide was injected and reacted with stirring at 160-165 ° C. for about 6 hours. After completion of the reaction, the obtained polyoxyethylene vitamin E was reacted with 200 g (3.45 mol) of propylene oxide at 155 to 160 ° C. for 8 hours in the presence of 0.15 g of KOH (99.9%) to obtain a pale yellow solid. After completion of the reaction, the reaction mixture was evacuated three times with nitrogen to remove unreacted ethylene oxide, propylene oxide, and by-product 1,4-dioxane. The reaction mixture was cooled to about 45 ° C., and a small amount of citric acid was added to neutralize the alkaline component added to the catalyst. . Unreacted vitamin E was removed with toluene and purified with Sephadex LH-50 column chromatography using chloroform-methanol (1: 1) as an eluting solvent to obtain 291.2 g of solid polyoxypropylenepolyoxyethylene vitamin E (4). The analysis results of this liquid product are as follows.
분석결과Analysis
(1) 성상 : 실온에서 반고상인 미황색의 물질(1) Appearance: A pale yellow substance that is semisolid at room temperature.
(2) 원소분석결과 : C679H1349O252분자량 (상대분자량)으로서(2) Elemental analysis: C 679 H 1349 O 252 as molecular weight (relative molecular weight)
계산치(%) : C : 60.23, H : 9.97, N : 0.00Calculated Value (%): C: 60.23, H: 9.97, N: 0.00
실측치(%) : C : 60.58, H : 10.02, N : 0.04Found (%): C: 60.58, H: 10.02, N: 0.04
(3) 반응수율 : 94.0%(3) Yield of reaction: 94.0%
(4) 부가된 에틸렌옥사이드 몰수(평균) : 100 몰(4) Number of moles of added ethylene oxide (average): 100 moles
(5) 부가된 프로필렌옥사이드 몰수(평균) : 150 몰(5) Number of moles of propylene oxide added (average): 150 moles
실시예 5: 폴리옥시프로필렌폴리옥시에틸렌[POP(200)-POE(150)] 비타민 E(5) 제조Example 5 Preparation of Polyoxypropylene Polyoxyethylene [POP (200) -POE (150)] Vitamin E (5)
2ℓ의 2중 스테인레스스틸로 된 오토클레이브에 합성비타민 E (dl α-토코페롤) 4.3g (0.01 mol)을 넣고 다시 고순도의 KOH (99.9%) 0.2 g을 넣어 77 ℃까지가열하면서 진공도가 약 740 mmHg가 되게 하여 약 30분간 탈수한 다음 에틸렌옥사이드 79.2g (1.8 mol)을 압입하여 160-165 ℃에서 약 6시간 동안 교반하면서 반응시켰다. 반응완료 후 고상의 반응물을 얻고 상기 반응물을 다시 KOH (99.9%) 0.15 g 존재하에 9 시간 동안 155-160 ℃온도에서 프로필렌옥사이드 139.2g (2.4 mol)과 반응시켜 미황색의 반고체를 얻었다. 반응종결 후 질소로 3회 배기시켜 미반응 에틸렌옥사이드와 프로필렌옥사이드 및 부생한 1, 4-디옥산을 제거한 다음 반응혼합물을 약 50℃로 냉각한 후 초산을 미량 가하여 촉매로 가해진 알칼리 성분을 중화시켰다. 미반응 비타민 E를 톨루엔으로 제거한 후 클로로포름-메탄올 (1:1)을 용출용매로한 세파덱스 LH-50 칼럼크로마토그라피로 정제하여 208.2g의 액상 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(5)를 얻었으며 이 액상 생성물의 분석결과는 하기와 같다.4.3 g (0.01 mol) of synthetic vitamin E (dl α-tocopherol) was added to a 2-liter stainless steel autoclave, followed by 0.2 g of high purity KOH (99.9%). After dehydration for about 30 minutes, and then 79.2g (1.8 mol) of ethylene oxide was indented and reacted with stirring at 160-165 ℃ for about 6 hours. After the reaction was completed, a solid reaction product was obtained, and the reaction product was reacted with 139.2 g (2.4 mol) of propylene oxide at 155-160 ° C. for 9 hours in the presence of 0.15 g of KOH (99.9%) to obtain a slightly yellow semi-solid. After completion of the reaction, the reaction mixture was evacuated three times with nitrogen to remove unreacted ethylene oxide, propylene oxide, and byproducts 1 and 4-dioxane. The reaction mixture was cooled to about 50 ° C., and a small amount of acetic acid was added to neutralize the alkaline component added to the catalyst. . Unreacted vitamin E was removed with toluene, and then purified by Sephadex LH-50 column chromatography using chloroform-methanol (1: 1) as an eluting solvent to obtain 208.2 g of liquid polyoxypropylenepolyoxyethylene vitamin E (5). The analysis results of this liquid product are as follows.
분석결과Analysis
(1) 성상 : 실온에서 반고상인 미황색의 물질(1) Appearance: A pale yellow substance that is semisolid at room temperature.
(2) 원소분석결과 : C92H1849O352분자량 (상대분자량)으로서(2) Elemental analysis result: C 92 H 1849 O 352 as molecular weight (relative molecular weight)
계산치(%) : C : 59.84, H : 9.93, N : 0.00Calculated Value (%): C: 59.84, H: 9.93, N: 0.00
실측치(%) : C : 60.05, H : 10.34, N : 0.04Found (%): C: 60.05, H: 10.34, N: 0.04
(3) 반응수율 : 93.5%(3) Yield of reaction: 93.5%
(4) 부가된 에틸렌옥사이드 몰수(평균) : 150 몰(4) Number of moles of added ethylene oxide (average): 150 moles
(5) 부가된 프로필렌옥사이드 몰수(평균) : 200 몰(5) Number of moles of propylene oxide added (average): 200 moles
실시예 6: 폴리옥시프로필렌폴리옥시에틸렌[POP-POE] 비타민 E의 생체외 항산화력 조사Example 6 In Vitro Antioxidant Activity of Polyoxypropylene Polyoxyethylene [POP-POE] Vitamin E
본 발명의 신규한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 항산화력은 리놀산(linoleic acid)를 이용하여 측정하였다. 항산화력 시험에 사용된 리놀산은 시약급으로서 순도가 리놀산이 78%이고 리놀레인산이 12.5% 함유된 미국 Sigma사의 시약급이었다.The antioxidant power of the novel polyoxypropylene polyoxyethylene vitamin E of the present invention was measured using linoleic acid. Linoleic acid used in the antioxidant test was reagent grade reagent grade 78% linoleic acid and 12.5% linoleic acid.
항산화력 실험을 위해 실시예 1, 2, 3, 4 및 5의 본 발명 폴리옥시프로필렌폴리옥시에틸렌 비타민 E들과 대조물질로서 비타민 E, 비타민 E 아세테이트 및 선출원된 폴리옥시프로필렌폴리옥시에틸렌 비타민 E들 등을 각각 0.5% 농도로 리놀산에 첨가한 후 40 ℃의 항온조에 보관하고 2일 후 및 20일 후에 과산화물가를 측정하였다. 상세히 설명하면 시료 1.0 g을 250 mL의 삼각플라스크에 넣고 클로로포름 10 mL를 넣어 시료를 녹이고 빙초산 15 mL와 요드화칼륨 포화용액 1 mL를 넣은 후 마개를 하고 격렬히 흔든 다음, 어두운 곳에 5분간 방치하였다. 다시 방치해 두었던 삼각플라스크에 증류수 75 mL를 가한 후 플라스크의 마개를 하고 격렬히 흔들고 전분 용액을 지시약으로 하여 유리된 요오드를 0.01 N 치오황산나트륨 용액으로 적정하여 무색이 되는 점을 종말점으로 하였고 과산화물가는 하기와 같이 측정하였다.Vitamin E, Vitamin E Acetate and Pre-Pried Polyoxypropylene Polyoxyethylene Vitamin Es as Controls of the Invention Polyoxypropylenepolyoxyethylene Vitamin Es of Examples 1, 2, 3, 4 and 5 for Antioxidant Testing And the like were added to linoleic acid at a concentration of 0.5%, respectively, and then stored in a thermostat at 40 ° C., and the peroxide value was measured after 2 days and 20 days. In detail, 1.0 g of the sample was placed in a 250 mL Erlenmeyer flask, 10 mL of chloroform was dissolved to dissolve the sample, 15 mL of glacial acetic acid and 1 mL of saturated potassium iodide were added. The cap was shaken vigorously, and left in a dark place for 5 minutes. 75 mL of distilled water was added to the Erlenmeyer flask, which was left to stand again, and the flask was capped and shaken vigorously. The starch solution was used as an indicator, and the free iodine was titrated with 0.01 N sodium thiosulfate solution as the end point. Measured together.
S : 검체의 0.01N 치오황산나트륨 소비량 (mL)S: 0.01N sodium thiosulfate consumption of sample (mL)
B : 공시험의 0.01N 치오황산나트륨 소비량 (mL)B: 0.01 N sodium thiosulfate consumption in blank test (mL)
실험결과, 표 1에 나타내 바와 같이 실시예 1에서 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(1), 실시예 2에서 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(2) 및 실시예 3에서 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E (3)는 비교 대조군인 선출원된 발명특허의 폴리옥시프로필렌폴리옥시에틸렌 비타민 E들보다 훨씬 우수한 항산화력을 나타냈고 잘 알려진 생리활성 항산화제인 비타민 E 보다 우수한(실시예 1 및 2) 또는 유사한 (실시예 3) 효과를 나타내었으며 실시예 4와 5에서 제조한 분자량이 큰 폴리옥시프로필렌폴리옥시에틸렌 비타민 E(4,5)의 경우도 비교 대조군인 선출원의 폴리옥시에틸렌폴리옥시프로필렌 비타민 E 보다 우수한 항산화 효과를 나타내었다. 이를 표 1에 정리하였다.As a result of the experiment, as shown in Table 1, polyoxypropylene polyoxyethylene vitamin E (1) prepared in Example 1, polyoxypropylene polyoxyethylene vitamin E (2) prepared in Example 2 and prepared in Example 3 One polyoxypropylenepolyoxyethylene vitamin E (3) exhibited much better antioxidant power than the comparative control polyoxypropylenepolyoxyethylene vitamin Es of the prior invention and was superior to the well-known bioactive antioxidant vitamin E. Examples 1 and 2) or a similar (Example 3) effect and the high molecular weight polyoxypropylene polyoxyethylene vitamin E (4,5) prepared in Examples 4 and 5 is also a comparative control polyoxy of the prior application It showed better antioxidant effect than ethylene polyoxypropylene vitamin E. This is summarized in Table 1.
특히,에틸렌옥사이드기를 부가하지 않은 경우 즉, m=0 일때 프로필렌옥사이드기의 몰수 n=2, 5에서 비타민 E 토코페롤 자체보다도 우수한in vivo항산화 효과를 나타내었는데 이는 다음과 같이 설명할 수 있다.In particular, when the ethylene oxide group is not added, that is, when m = 0, the number of moles of propylene oxide group n = 2, 5 showed an in vivo antioxidant effect superior to the vitamin E tocopherol itself, which can be described as follows.
토코페롤에 POE 또는 POP가 부가된 양친매성 물질에서 OH 기의 수소 라디칼이 해리되어 프리라디칼 스캐빈징효과는 E.O보다는 P.O가 P.O기의 메칠기 전자공여효과로 인하여 보다 용이한데, 이것은 원래 소수성인 토코페롤의 크로만링과 이에 부가된 기가 같은 소수성 성질일 때 크로만링 전자의 비국재화(delocalization) 효과가 증가하여 수소 라디칼이 쉽게 발생될 수 있기 때문으로 생각된다. 따라서 보다 소수성인 P.O가 토코페롤에 직접 부가중합되든가 즉, m=0인 경우 또는 에틸렌옥사이드(E.O)가 최소한의 몰수로 부가중합 될 때 즉 m=1인 경우 메칠기의 전자 공여효과와 토코페롤의 전자의 비국재화 상승효과로 인해 m=2이상에서 보다 우수한 항산화 효과를 나타낸 것으로 볼 수 있다.The free radical scavenging effect by dissociating the hydrogen radicals of the OH groups in the amphiphilic substance with POE or POP added to tocopherol is easier due to the methyl group electron donating effect of PO groups than EO, which is originally hydrophobic. It is believed that hydrogen radicals can be easily generated due to the increase in the delocalization effect of the Chroming-ring electrons when the Chroming and the added groups have the same hydrophobic nature. Therefore, when the more hydrophobic PO is directly polymerized to tocopherol, i.e., when m = 0 or when ethylene oxide (EO) is added to a minimum molar number, i.e., m = 1, the electron donating effect of methyl group and the electron of tocopherol Due to the non-localization synergistic effect of m = 2 it can be seen that the better antioxidant effect.
실시예 7. 폴리옥시프로필렌폴리옥시에틸렌[POP-POE]비타민E가 자외선에 의한 홍반발생과 멜라닌 색소형성에 미치는 영향 조사Example 7 Investigation of the Effect of Polyoxypropylene Polyoxyethylene [POP-POE] Vitamin E on the Erythema and Melanin Pigmentation by UV Light
본 발명의 폴리옥시프로필렌폴리옥시에틸렌(POP-POE) 비타민 E는 생체외(in vitro) 실험에서 항산화 특성이 선출원된 POP-POE 비타민 E보다 우수한 것으로 확인되었으나 본 실시예에서는 생체(in vivo)에서의 항산화 활성 및 항염증 활성을 알아보기 위하여 선출원된 POP-POE 비타민 E와 실시예 1∼3에서 제조한 폴리옥시프로필렌폴리옥시에틸렌을 비교하여 실험하였다.Polyoxypropylene polyoxyethylene (POP-POE) vitamin E of the present invention was confirmed that the antioxidant properties are superior to the pre-applied POP-POE vitamin E in vitro experiments in the present embodiment in vivo In order to examine the antioxidant and anti-inflammatory activity of the pre-applied POP-POE vitamin E and the polyoxypropylene polyoxyethylene prepared in Examples 1 to 3 were compared.
표 2에 나타낸 바와 같이 시험예 1, 2, 3과 비교시험예 1, 2, 3, 4를 각각 20∼30세의 정상인 남자 5명과 여자 5명 총 10명의 피부에 0.5g씩 4cm2에 도포하고 자외선을 약 4 MED(minimum erythema dose ;최소 홍반발생 조사량)로 조사하여 홍반발생과 멜라닌색소형성에 미치는 효과를 측정하였다. 이때, 자외선 조사기는 Phillips 20W 램프를 장착한 독일의 Waldmann UV 800 (Herbert Waldmann Gmbh & Co.)을 사용했으며 10명에 대한 평균치를 종합한 결과를 각각 홍반지수(erythema index)(표 3)와 멜라닌색소지수(melanin index)(표 4)로 나타내었다. 각 지수 값은 시험 시 피부에 대해 독일의 Maxameter MX16 (CK Electronic Gmbh) 색차계로 측정한 피부 밝기의 상대적인 수치이다. 일반적으로 홍반은 자외선 조사 1일 후에 최고에 도달하는 것으로 알려져 있는데, 본 실시예에서 초기 1일 후에 선출원된 POP-POE 비타민 E 및 비타민 E 유도체인 비타민 E 아세테이트를 사용한 대조군인 비교시험예 1, 2, 4에 비하여 시험예 1, 2, 3이 홍반발생이 적었고 특히, 비타민 E를 사용한 비교시험예 3 보다도 홍반발생이 적었으며 자외선 조사 5일후와 10일 후에는 전 조사부위의 홍반지수의 차이가 줄어들었다. 표 3의 결과에 따르면 시험예 1, 2, 3이 홍반발생을 억제하여 항염증효과 및 항산화효과가 있으며 특히 시험예 1, 2, 3의 본 발명 POP-POE비타민 E는 선출원한 POP-POE 비타민 E 뿐만 아니라 기존의 안정한 생리활성 항산화제로 알려진 비타민 E보다도 더 우수한 항염증 및 항산화 효과가 있음을 알 수 있다.As shown in Table 2, Test Examples 1, 2, and 3 and Comparative Test Examples 1, 2, 3, and 4, respectively, 0.5 g 4 cm each of 5 males and 5 females of 20 to 30 years of age.2UV light was applied at about 4 MED (minimum erythema dose) to determine the effect on erythema and melanogenesis. The UV irradiator used a German Waldmann UV 800 (Herbert Waldmann Gmbh & Co.) with a Phillips 20W lamp and synthesized the average value for 10 people. The erythema index (Table 3) and melanin It is shown by the melanin index (Table 4). Each index value is a relative value of skin brightness measured with a German Maxameter MX16 (CK Electronic Gmbh) colorimeter on the skin under test. In general, erythema is known to reach the highest after 1 day of ultraviolet irradiation, Comparative Example 1, 2, which is a control group using the pre-applied POP-POE vitamin E and vitamin E derivative vitamin E acetate after the first day The erythema incidence in Test Examples 1, 2, and 3 was less than that in, and 4, and the erythema incidence was less than that in Comparative Test Example 3 using vitamin E. Shrunk. According to the results of Table 3, Test Examples 1, 2, and 3 inhibit erythema development, and thus have an anti-inflammatory effect and an antioxidant effect. In particular, the present invention POP-POE Vitamin E of Test Examples 1, 2, and 3 is a pre-populated POP-POE vitamin As well as E, it can be seen that there is an excellent anti-inflammatory and antioxidant effect than vitamin E, known as a stable bioactive antioxidant.
멜라닌색소는 홍반과는 달리 일반적으로 자외선 조사 5일 이후에 증가한다.표 4의 결과에 따르면 비교시험예 1, 2, 4의 경우 초기 1일 후에 비하여 자외선 조사 5일 후와 10일 후에 멜라닌색소지수가 현저히 증가한 반면 시험예 1, 2, 3을 사용한 경우 자외선 조사 1일 후, 5일 후, 10일 후가 모두 비슷하여 멜라닌색소형성을 억제하였음을 알 수 있었고, 효과가 있는 것으로 알려진 비타민 E를 사용한 경우보다 자외선 조사 1일 후, 5일 후, 10일 후의 멜라닌색소형성 차이가 적었다. 다시 말해서 본 시험예 1, 2, 3은 선출원한 비교 대조군의 POP-POE 비타민 E뿐만 아니라 안정한 생리활성 항산화제인 비타민 E를 사용한 비교시험예 3보다도 우수한 멜라닌 색소형성 억제 효과를 나타냄을 알 수 있다.Unlike erythema, melanin pigments generally increase after 5 days of UV irradiation. According to the results of Table 4, melanin pigments after 5 days and 10 days of UV irradiation were compared with those of Comparative Test Examples 1, 2, and 4 after the initial 1 day. Significantly increased the index, while using Test Examples 1, 2, and 3 were similar after 1, 5, and 10 days of UV irradiation, indicating that melanin formation was inhibited. Vitamin E is known to be effective. The melanin pigmentation difference was less after 1 day, after 5 days, and after 10 days of ultraviolet irradiation than when using. In other words, Test Examples 1, 2, and 3 show melanin pigmentation inhibitory effects superior to Comparative Test Example 3 using vitamin E, which is a stable physiologically active antioxidant, as well as POP-POE vitamin E of the comparative control group.
즉, 본 발명 POP-POE비타민 E는 생체외(in vitro)에서 뿐만 아니라 생체내(in vivo)에서도 홍반발생과 멜라닌색소형성을 예방하는 효과가 있으며, 비타민 E와 선출원한 POP-POE 비타민 E와 비교해보아도 항염증 활성과 항산화 활성에 있어서 뛰어난 효과가 있음을 알 수 있다.That is, the present invention POP-POE vitamin E is effective in preventing rash occurs and melanin formation as well as in vitro (in vitro) in vivo (in vivo), vitamin E and the earlier application the POP-POE vitamin E In comparison, it can be seen that there is an excellent effect on anti-inflammatory activity and antioxidant activity.
* 각 시험용액은 녹인 후 50℃에서 팁-타입 고주파기로서 5분간 작동하여 제조하고 사용부위에 펴 바름.* After each test solution is melted, it is manufactured by operating for 5 minutes as a tip-type radio frequency equipment at 50 ℃ and spread on the used part.
실시예 8: 폴리옥시프로필렌폴리옥시에틸렌(POP-POE) 비타민 E의 계면활성작용 조사Example 8 Investigation of the Surfactant Activity of Polyoxypropylene Polyoxyethylene (POP-POE) Vitamin E
본 발명의 신규한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 계면활성작용을 알아보기 위하여 실시예 1 ~ 5에서 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E의 기포력 및 기포 안정도, 베시클형성 및 유화 실험을 선출원한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E와 비교하여 실험하였다.Foaming force and bubble stability, vesicle formation and emulsification experiment of polyoxypropylenepolyoxyethylene vitamin E prepared in Examples 1 to 5 to investigate the surface active action of the novel polyoxypropylene polyoxyethylene vitamin E of the present invention Was compared with the polyoxypropylene polyoxyethylene vitamin E pre- filed.
실험예 1: 기포력 및 기포안정도 측정Experimental Example 1: Measurement of Bubble Force and Bubble Stability
기포력 및 기포안정도는 다이나믹 폼테스트(dynamic foam test) 방법으로 실시하였다. 눈금이 매겨진 내경 10cm의 2ℓ 실린더에 0.1% 수용액 400cc를 넣고 20℃에서 1000rpm으로 아지믹서를 1분 회전시킨 후 기포층의 높이를 기포력으로 하고 교반 후 3분 방치한 다음 기포층 부피에 대한 교반직후의 기포층 부피 백분율을 기포안정도로 하여 측정하였다. 실험결과 표 5에 나타낸 바와 같이, 실시예 1, 2 및 3에서 제조한 비교적 저분자량의 본 발명 폴리옥시프로필렌폴리옥시에틸렌 비타민E는 대조군인 선출원한 POP(2)-POE(5),POP(5)-POE(10) 비타민 E에 비하여, 아주 미약한 기포력과 낮은 기포안정도를 나타내었다. 이것은 본 발명의 비교적 저분자량의 POP-POE 비타민 E가 선출원된 POP-POE 비타민 E보다도 소수성인 것을 나타내는 것이다. 한편, 실시예 4 및 5의 본 발명의 POP-POE 비타민 E는 상당한 기포력과 기포안정도를 나타내었으며 비교 대조군의 POP(100)-POE(150) 비타민 E보다는 상당히 낮은 기포력과 기포안정도를 나타내었다. 이것도 역시 본 발명의 비교적 고분자량의 폴리옥시에틸렌폴리옥시프로필렌 비타민 E의 소수성이 상당히 향상되었음을 의미한다.Bubble strength and bubble stability were performed by the dynamic foam test method. 400cc of 0.1% aqueous solution was put into a 2 l cylinder with a graduated inner diameter of 10cm and the azimixer was rotated for 1 minute at 1000rpm at 20 ° C. The bubble layer volume percentage immediately after was measured as bubble stability. Experimental results As shown in Table 5, the comparatively low molecular weight polyoxypropylene polyoxyethylene vitamin E prepared in Examples 1, 2, and 3 was used as a control group of the pre-populated POP (2) -POE (5), POP ( 5) -POE (10) Compared to vitamin E, it showed very weak foaming power and low foam stability. This indicates that the relatively low molecular weight POP-POE vitamin E of the present invention is hydrophobic than the pre-populated POP-POE vitamin E. On the other hand, the POP-POE vitamin E of the present invention of Examples 4 and 5 showed a significant foaming power and bubble stability and significantly lower foaming and bubble stability than the POP (100) -POE (150) vitamin E of the comparative control group It was. This also means that the hydrophobicity of the relatively high molecular weight polyoxyethylenepolyoxypropylene vitamin E of the present invention is significantly improved.
실험예 2: 베시클(vesicle) 형성실험Experimental Example 2: vesicle formation experiment
본 발명의 실시예 1 및 2의 화합물에서 얻은 폴리옥시프로필렌폴리옥시에틸렌 비타민 E에 대한 또 다른 계면활성 특성을 알아보기 위하여 각각을 0.5% 함유한 10% 에탄올 수용액을 이용하여 베시클 (vesicle) 형성 실험을 실시하였다. 실시예1 및 2의 본 발명 화합물은 자체가 소수성이므로 수용액만으로서는 베시클을 형성할 수 없기 때문에 10% 에탄올 수용액을 이용하였다. 25 ℃의 수용액을 팁타입 (tip type) 고주파기로 교반한 후 시료와 동량의 2% 우라닐아세테이트 (uranyl acetate) 수용액과 혼합하여 손으로 흔들어 준 후 탄소가 코팅된 200 메시 (mesh) 구리망 (copper grid) 위에 시료를 적하하고 실온에서 약 20분간 건조시킨 후 필립스 (Philips)사의 전자현미경으로써 관찰하였다. 이때 출력은 80 KV였다. 실험결과, 놀랍게도 본 발명의 실시예 1 및 2의 화합물은 분명한 페쇄구형 베시클을 형성함을 알 수 있었다. 도 3은 실시예 1의 화합물의 베시클형성 사진이다.Formation of vesicles using 10% aqueous ethanol solution containing 0.5% of polyoxypropylene-polyoxyethylene vitamin E in order to investigate further surfactant properties of polyoxypropylenepolyoxyethylene vitamin E obtained in the compounds of Examples 1 and 2 of the present invention The experiment was conducted. Since the compounds of the present invention of Examples 1 and 2 are themselves hydrophobic, no vesicles can be formed by aqueous solution alone, and 10% ethanol aqueous solution was used. After stirring a 25 ℃ aqueous solution with a tip type high frequency equipment and mixed with a sample of the same amount of 2% uranyl acetate (aqueous aqueous solution) and shaken by hand, the carbon-coated 200 mesh copper mesh ( The sample was added dropwise onto a copper grid, dried at room temperature for about 20 minutes, and observed with an electron microscope of Philips. The output was 80 KV. As a result, it was surprisingly found that the compounds of Examples 1 and 2 of the present invention formed a clear blocked sphere vesicle. Figure 3 is a vesicle formation picture of the compound of Example 1.
실험예 3 : 유화실험Experimental Example 3: Emulsification Experiment
본 발명의 실시예 4 및 실시예 5에서 제조한 폴리옥시에틸렌폴리옥시프로필렌 비타민 E의 유화제로서의 성질을 정확히 알기 위해서 유화실험을 실시하였다. 표 6에 나타낸 바와 같이, 유동파라핀#70 (Witco Chem.미국) 및 폴리디메칠실로세인 검과 오일(SE 72 와 Viscasil 60M, GE Silicone 미국)을 각각 유상으로 하는 수중유형 처방을 1 및 2로 표시하였다. 유화제를 포함하는 오일상과 수상을 각각 70℃로 가열하였고 호모믹싱을 하면서 오일상을 수상에 첨가하였다. 유화 후 30℃로 냉각하여 투명 용기에 충진하고 40℃에 보관한 다음 60일후 안정도를 체크하였다. 유화 안정도는 전체 유화물의 부피 대 분리되지 않고 안정한 부피의 백분율(%)로 표시하였다.In order to know exactly the properties of the polyoxyethylene polyoxypropylene vitamin E prepared in Examples 4 and 5 of the present invention as an emulsifier, an emulsification experiment was conducted. As shown in Table 6, oil-in-water formulations with fluid paraffin # 70 (Witco Chem. USA) and polydimethylsiloseine gum and oil (SE 72 and Viscasil 60M, GE Silicone USA), respectively, were formulated as 1 and 2. Indicated. The oil phase containing the emulsifier and the aqueous phase were each heated to 70 ° C. and the oil phase was added to the aqueous phase with homomixing. After emulsification, the mixture was cooled to 30 ° C, filled in a transparent container, stored at 40 ° C, and then checked for stability after 60 days. Emulsification stability is expressed as a percentage of the volume of the total emulsion versus the volume that is not isolated and stable.
표 7에서 알 수 있는 바와 같이 본 실험에 사용된 실시예 4 및 5의 비교적 고분자량의 본 발명 POP-POE 비타민 E는 기 발명특허 출원된 POP-POE 비타민 E에서 소수성을 향상시킨 것으로서 선출원한 POP-POE 비타민 E보다 유동파라핀 및 실리콘 검과 오일을 각각 오일상으로 하는 수중유형 유화에서 향상된 유화 안정도를 나타내었다.As can be seen in Table 7, the relatively high molecular weight of the present invention POP-POE vitamin E of Examples 4 and 5 used in this experiment is a POP that has been selected as an improved hydrophobicity in the previously patented POP-POE vitamin E Emulsion stability was improved in oil-in-water emulsions with fluid paraffin, silicone gum and oil as oil phase, respectively, than -POE vitamin E.
이는 비교적 높은 에틸렌옥사이드(EO)몰수에서는 친수성은 향상되지만 프로필렌옥사이드 몰수 n=1∼100까지에서는 소수성이 비교적 약하므로 프로필렌옥사이드 몰수 n=101∼200으로 높임으로써 소수성이 보다 강화되어 우수한 유화력을 나타낸 것으로 설명할 수 있다.This shows that hydrophilicity is improved at relatively high moles of ethylene oxide (EO), but hydrophobicity is relatively weak at moles of propylene oxide n = 1 to 100. It can be explained.
이상 상기 실시예 및 실험예를 통하여 설명한 바와 같이, 항산화 생리활성 비타민 E의 하이드록시기(OH)에 에틸렌옥사이드기를 부가하지 않거나 또는 1몰을 부가하고(m=0∼1인 경우) 얻은 폴리옥시에틸렌 비타민 E에 다시 프로필렌옥사이드(n=1∼200)를 부가중합시켜 얻은 폴리옥시프로필렌폴리옥시에틸렌 비타민 E는in vitro및in vivo에서 항산화력이 에틸렌옥사이기의 몰수가 2 이상인 경우에서보다 향상되는 효과가 있고, 특히 에틸렌옥사이드기의 몰수가 0∼1이고 프로필렌옥사이드기가 2, 5, 10에서 획득한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E는 친수성이 상당히 있어 베시클(vesicle)을 형성하는 등 우수한 계면활성을 나타내는 효과가 있으며, 또한 항산화 생리활성 비타민 E의 하이드록시기(OH)에 에틸렌옥사이드기를 부가하고(m=0∼150인 경우) 얻은 폴리옥시에틸렌 비타민 E에 다시 프로필렌옥사이드를 101몰 이상에서부터 200몰을 부가중합시킴으로써 제조한 폴리옥시프로필렌폴리옥시에틸렌 비타민 E는 친수성과 소수성이 균형있게 강화되어 우수한 유화력과 항산화력을 나타내는 뛰어난 효과가 있으므로 화장품산업, 식품 산업 및 의약품 산업상 매우 유용한 발명인 것이다.As described above in the above Examples and Experimental Examples, the polyoxy obtained by not adding ethylene oxide group or adding 1 mole (m = 0 to 1) to the hydroxyl group (OH) of the antioxidant bioactive vitamin E Polyoxypropylene polyoxyethylene vitamin E obtained by addition polymerization of propylene oxide (n = 1 to 200) to ethylene vitamin E has improved antioxidant capacity in vitro and in vivo than when mole number of ethylene oxy group is 2 or more. In particular, the polyoxypropylene polyoxyethylene vitamin E obtained by moles of ethylene oxide groups from 0 to 1 and propylene oxide groups from 2, 5, and 10 has considerable hydrophilicity to form vesicles. Obtained by adding an ethylene oxide group to the hydroxyl group (OH) of the antioxidant bioactive vitamin E (when m = 0 to 150). Polyoxypropylene polyoxyethylene vitamin E prepared by adding and polymerizing propylene oxide from 101 moles or more to 200 moles of reoxyethylene vitamin E has an excellent effect of excellent emulsification and anti-oxidation properties due to a good balance of hydrophilicity and hydrophobicity. It is a very useful invention in the cosmetic industry, food industry and pharmaceutical industry.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2001-0004180A KR100453727B1 (en) | 2001-01-30 | 2001-01-30 | Novel polyoxypropylenepolyoxyethylene vitamin E and process for preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2001-0004180A KR100453727B1 (en) | 2001-01-30 | 2001-01-30 | Novel polyoxypropylenepolyoxyethylene vitamin E and process for preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20020063650A true KR20020063650A (en) | 2002-08-05 |
| KR100453727B1 KR100453727B1 (en) | 2004-10-20 |
Family
ID=27692686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-2001-0004180A KR100453727B1 (en) | 2001-01-30 | 2001-01-30 | Novel polyoxypropylenepolyoxyethylene vitamin E and process for preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR100453727B1 (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03206089A (en) * | 1990-01-05 | 1991-09-09 | Eisai Co Ltd | New vitamin e derivative and production thereof |
| US5352696A (en) * | 1993-01-22 | 1994-10-04 | Pacific Corporation | Quaternary nitrogen-containing vitamin E derivatives and uses thereof |
| CA2148148A1 (en) * | 1994-05-20 | 1995-11-21 | Kazumi Ogata | Tocopherol derivatives |
| KR20000000840A (en) * | 1998-06-03 | 2000-01-15 | 김영대 | NOVEL POLYOXYPROYLENEPOLYOXYETHYlLENE VITAMIN E AND PROCESS FOR PRODUCING THE SAME |
-
2001
- 2001-01-30 KR KR10-2001-0004180A patent/KR100453727B1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| KR100453727B1 (en) | 2004-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2501267B2 (en) | Polyethoxylated vitamin E, method for producing the same, and use thereof | |
| KR20000000840A (en) | NOVEL POLYOXYPROYLENEPOLYOXYETHYlLENE VITAMIN E AND PROCESS FOR PRODUCING THE SAME | |
| EP1245608B1 (en) | Polyethylene glycol and process for producing the same | |
| US6521662B2 (en) | Ceramide-like compounds having antioxidant property and a method for preparation thereof, and a cosmetic composition containing the same | |
| RU2418573C2 (en) | Cosmetic preparation | |
| JPH0768101B2 (en) | Cosmetic composition containing polyethoxylated vitamin E | |
| KR100453727B1 (en) | Novel polyoxypropylenepolyoxyethylene vitamin E and process for preparation thereof | |
| KR100829890B1 (en) | Novel retinol derivatives, preparation method thereof and cosmetic composition for improving wrinkles | |
| JP2001247585A (en) | Tocopherol derivative, intermediate for the same, method of producing the same, and application for the same | |
| JP4432127B2 (en) | Method for producing oligoalkyloxirane derivative and humectant | |
| US7144919B1 (en) | Polyoxyethylene-polyoxypropylene vitamin E and process for preparation thereof | |
| KR101061911B1 (en) | PEGylated betulin derivatives and cosmetic compositions comprising the same | |
| AU2004290876B2 (en) | Use of perfluoropolyethers phosphates as stabilizing agents for polyphenols in cosmetic and/or dermatological compositions | |
| WO2023245459A1 (en) | Anti-oxidizing composition comprising a thiopyridinone compound | |
| KR101451401B1 (en) | Conjugate of vitamin C with vitamin E and antioxidant comprising the same | |
| KR100328535B1 (en) | Polyoxyethylene-polyoxypropylene Vitamine E and process for preparation thereof | |
| KR100356676B1 (en) | Lyotropic liquid crystalline compound and a method for preparation thereof, and cosmetic composition containing thereof | |
| EP1531156A1 (en) | Method for synthesis of silylated ascorbic acid derivatives | |
| KR20170076091A (en) | Salicylic acid derivative compounds, preparation method thereof, and whitening cosmetic composition comprising the same | |
| JP2008007449A (en) | Dihydroflavonol compound and its manufacturing method, and antiinflammatory agent, antioxidant and skin cosmetic | |
| MXPA00012049A (en) | Novel polyoxypropylenepolyoxyethylene vitamin e and preparation thereof | |
| JPS5822125B2 (en) | cosmetics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| PA0109 | Patent application |
Patent event code: PA01091R01D Comment text: Patent Application Patent event date: 20010130 |
|
| PA0201 | Request for examination | ||
| PG1501 | Laying open of application | ||
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20030526 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20040730 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20041011 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20041012 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20071005 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20080930 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20091012 Start annual number: 6 End annual number: 6 |
|
| PR1001 | Payment of annual fee |
Payment date: 20101011 Start annual number: 7 End annual number: 7 |
|
| PR1001 | Payment of annual fee |
Payment date: 20111010 Start annual number: 8 End annual number: 8 |
|
| FPAY | Annual fee payment |
Payment date: 20121010 Year of fee payment: 9 |
|
| PR1001 | Payment of annual fee |
Payment date: 20121010 Start annual number: 9 End annual number: 9 |
|
| FPAY | Annual fee payment |
Payment date: 20140411 Year of fee payment: 10 |
|
| PR1001 | Payment of annual fee |
Payment date: 20140411 Start annual number: 10 End annual number: 10 |
|
| LAPS | Lapse due to unpaid annual fee | ||
| PC1903 | Unpaid annual fee |
Termination category: Default of registration fee Termination date: 20150909 |