JP6122646B2 - Topical skin preparation - Google Patents
Topical skin preparation Download PDFInfo
- Publication number
- JP6122646B2 JP6122646B2 JP2013010487A JP2013010487A JP6122646B2 JP 6122646 B2 JP6122646 B2 JP 6122646B2 JP 2013010487 A JP2013010487 A JP 2013010487A JP 2013010487 A JP2013010487 A JP 2013010487A JP 6122646 B2 JP6122646 B2 JP 6122646B2
- Authority
- JP
- Japan
- Prior art keywords
- external preparation
- salt
- skin
- tocopherol
- poe
- 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.)
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- 238000002360 preparation method Methods 0.000 title claims description 58
- 230000000699 topical effect Effects 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims description 50
- -1 tocopherol phosphate ester Chemical class 0.000 claims description 50
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 47
- 229930003799 tocopherol Natural products 0.000 claims description 45
- 239000011732 tocopherol Substances 0.000 claims description 45
- 235000010384 tocopherol Nutrition 0.000 claims description 45
- 229960001295 tocopherol Drugs 0.000 claims description 45
- 229910019142 PO4 Inorganic materials 0.000 claims description 36
- 239000002736 nonionic surfactant Substances 0.000 claims description 32
- 239000010452 phosphate Substances 0.000 claims description 32
- 239000002738 chelating agent Substances 0.000 claims description 19
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 18
- 239000002537 cosmetic Substances 0.000 claims description 16
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 239000011734 sodium Substances 0.000 claims description 6
- NFDRPXJGHKJRLJ-UHFFFAOYSA-N edtmp Chemical compound OP(O)(=O)CN(CP(O)(O)=O)CCN(CP(O)(O)=O)CP(O)(O)=O NFDRPXJGHKJRLJ-UHFFFAOYSA-N 0.000 claims description 5
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical group OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 claims description 4
- 229960003330 pentetic acid Drugs 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- VCVKIIDXVWEWSZ-YFKPBYRVSA-N (2s)-2-[bis(carboxymethyl)amino]pentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)N(CC(O)=O)CC(O)=O VCVKIIDXVWEWSZ-YFKPBYRVSA-N 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 33
- 235000021317 phosphate Nutrition 0.000 description 33
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 31
- 229920001451 polypropylene glycol Polymers 0.000 description 22
- 239000000203 mixture Substances 0.000 description 18
- 239000006210 lotion Substances 0.000 description 16
- 238000004040 coloring Methods 0.000 description 15
- 238000011156 evaluation Methods 0.000 description 15
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 15
- 238000009472 formulation Methods 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical class C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 238000006116 polymerization reaction Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 125000006353 oxyethylene group Chemical group 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 229940043375 1,5-pentanediol Drugs 0.000 description 2
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
- 239000003093 cationic surfactant Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 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 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- WCVRQHFDJLLWFE-UHFFFAOYSA-N pentane-1,2-diol Chemical compound CCCC(O)CO WCVRQHFDJLLWFE-UHFFFAOYSA-N 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 150000003611 tocopherol derivatives Chemical class 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 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 2
- GZIFEOYASATJEH-VHFRWLAGSA-N δ-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-VHFRWLAGSA-N 0.000 description 2
- BAERPNBPLZWCES-UHFFFAOYSA-N (2-hydroxy-1-phosphonoethyl)phosphonic acid Chemical compound OCC(P(O)(O)=O)P(O)(O)=O BAERPNBPLZWCES-UHFFFAOYSA-N 0.000 description 1
- DIWZKTYQKVKILN-VKHMYHEASA-N (2s)-2-(dicarboxymethylamino)pentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(C(O)=O)C(O)=O DIWZKTYQKVKILN-VKHMYHEASA-N 0.000 description 1
- FKKAGFLIPSSCHT-UHFFFAOYSA-N 1-dodecoxydodecane;sulfuric acid Chemical compound OS(O)(=O)=O.CCCCCCCCCCCCOCCCCCCCCCCCC FKKAGFLIPSSCHT-UHFFFAOYSA-N 0.000 description 1
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 1
- URDCARMUOSMFFI-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(2-hydroxyethyl)amino]acetic acid Chemical compound OCCN(CC(O)=O)CCN(CC(O)=O)CC(O)=O URDCARMUOSMFFI-UHFFFAOYSA-N 0.000 description 1
- XPFCZYUVICHKDS-UHFFFAOYSA-N 3-methylbutane-1,3-diol Chemical compound CC(C)(O)CCO XPFCZYUVICHKDS-UHFFFAOYSA-N 0.000 description 1
- SXFJDZNJHVPHPH-UHFFFAOYSA-N 3-methylpentane-1,5-diol Chemical compound OCCC(C)CCO SXFJDZNJHVPHPH-UHFFFAOYSA-N 0.000 description 1
- XDDAGVUFLQKVEA-SJTHZTAVSA-N 4-o-[(2r)-2-[(1s)-1,2-dihydroxyethyl]-3-hydroxy-5-oxo-2h-furan-4-yl] 1-o-[(2r)-2,5,7,8-tetramethyl-2-[(4r,8r)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] (z)-but-2-enedioate Chemical compound C([C@@](OC1=C(C)C=2C)(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)CC1=C(C)C=2OC(=O)\C=C/C(=O)OC1=C(O)[C@@H]([C@@H](O)CO)OC1=O XDDAGVUFLQKVEA-SJTHZTAVSA-N 0.000 description 1
- 0 CC(C)CCCC(C)CCCC(C)CCCC1(C)Oc2c(*)c(*)c(C(C3)C3*(O)=O)c(*)c2CC1 Chemical compound CC(C)CCCC(C)CCCC(C)CCCC1(C)Oc2c(*)c(*)c(C(C3)C3*(O)=O)c(*)c2CC1 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 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
- 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 1
- GZIFEOYASATJEH-UHFFFAOYSA-N D-delta tocopherol Natural products OC1=CC(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 229940120146 EDTMP Drugs 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N N-methylaminoacetic acid Natural products C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- OHHLQFCWNFSQEY-UHFFFAOYSA-N O.O.O.O.[Na].[Na].[Na].[Na].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O Chemical compound O.O.O.O.[Na].[Na].[Na].[Na].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O OHHLQFCWNFSQEY-UHFFFAOYSA-N 0.000 description 1
- ALQSHHUCVQOPAS-UHFFFAOYSA-N Pentane-1,5-diol Chemical compound OCCCCCO ALQSHHUCVQOPAS-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920002070 Pluronic® P 84 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- MSCCTZZBYHQMQJ-AZAGJHQNSA-N Tocopheryl nicotinate Chemical compound C([C@@](OC1=C(C)C=2C)(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)CC1=C(C)C=2OC(=O)C1=CC=CN=C1 MSCCTZZBYHQMQJ-AZAGJHQNSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- JUIUXBHZFNHITF-IEOSBIPESA-N [(2r)-2,5,7,8-tetramethyl-2-[(4r,8r)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] dihydrogen phosphate Chemical compound OP(=O)(O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C JUIUXBHZFNHITF-IEOSBIPESA-N 0.000 description 1
- ZAKOWWREFLAJOT-ADUHFSDSSA-N [2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] acetate Chemical group CC(=O)OC1=C(C)C(C)=C2OC(CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-ADUHFSDSSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- 229940066595 beta tocopherol Drugs 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008406 cosmetic ingredient Substances 0.000 description 1
- 229940099418 d- alpha-tocopherol succinate Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 235000010389 delta-tocopherol Nutrition 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229940105990 diglycerin Drugs 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- 108700003601 dimethylglycine Proteins 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000010382 gamma-tocopherol Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 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 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- XXMIOPMDWAUFGU-UHFFFAOYSA-N hexane-1,6-diol Chemical compound OCCCCCCO XXMIOPMDWAUFGU-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- GLOBUAZSRIOKLN-UHFFFAOYSA-N pentane-1,4-diol Chemical compound CC(O)CCCO GLOBUAZSRIOKLN-UHFFFAOYSA-N 0.000 description 1
- GTCCGKPBSJZVRZ-UHFFFAOYSA-N pentane-2,4-diol Chemical compound CC(O)CC(C)O GTCCGKPBSJZVRZ-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 229950009883 tocopheryl nicotinate Drugs 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 239000011590 β-tocopherol Substances 0.000 description 1
- 235000007680 β-tocopherol Nutrition 0.000 description 1
- 239000002478 γ-tocopherol Substances 0.000 description 1
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 1
- 239000002446 δ-tocopherol Substances 0.000 description 1
Landscapes
- Cosmetics (AREA)
Description
本発明は、皮膚外用剤に関する。 The present invention relates to an external preparation for skin.
従来、トコフェロール（ビタミンＥ）およびその種々の誘導体は、血行促進作用や高い抗酸化作用を有しており、肌荒れの予防、改善を目的として、化粧料等に配合されている。
トコフェロール誘導体の例としては、トコフェロールの水酸基をリン酸エステル化して水溶性を付与したトコフェロールリン酸エステルが知られており、これらは塩の形態で用いられることが多い。塩としては、ナトリウム塩等が一般的である。
Conventionally, tocopherol (vitamin E) and various derivatives thereof have a blood circulation promoting action and a high antioxidant action, and are blended in cosmetics and the like for the purpose of preventing and improving rough skin.
As an example of a tocopherol derivative, a tocopherol phosphate ester obtained by converting a hydroxyl group of tocopherol into a phosphate ester to impart water solubility is known, and these are often used in the form of a salt. As the salt, a sodium salt or the like is common.
トコフェロールリン酸エステル及び／又はその塩は両親媒性であるため生体への親和性が高く、皮膚等の生体組織への移行が速やかであることから、化粧料等の皮膚外用剤への適用が期待されている。
しかし、トコフェロールリン酸エステル及び／又はその塩を皮膚外用剤として製剤化すると、剤中で分解が起こり、外観に変化が生じるなどの問題があった。濁りの発生は、外観の変化だけでなく、皮膚外用剤を皮膚に適用した際の感触の悪化の原因ともなる。
トコフェロールリン酸エステル及び／又はその塩の分解は主として、水酸基にエステル結合したリン酸の加水分解により生じる。この分解により、水に不溶のトコフェロールが生じ、剤中で濁りを引き起こす。クリームのような白濁した剤型では目視で確認しにくいが、透明ローション系や美容液系では、濁りや沈殿、着色など、外観に変化が生じるという問題が発生する。
Tocopherol phosphates and / or their salts are amphipathic and have high affinity to living bodies, so that they can be rapidly transferred to living tissues such as skin, so that they can be applied to external preparations such as cosmetics. Expected.
However, when a tocopherol phosphate ester and / or a salt thereof is formulated as an external preparation for skin, there is a problem that decomposition occurs in the agent and changes in appearance. The occurrence of turbidity not only changes the appearance, but also causes a deterioration in touch when a topical skin preparation is applied to the skin.
Degradation of tocopherol phosphate ester and / or its salt is mainly caused by hydrolysis of phosphoric acid ester-bonded to a hydroxyl group. This decomposition produces tocopherol that is insoluble in water and causes turbidity in the agent. Although it is difficult to visually check in a cloudy dosage form such as a cream, the transparent lotion system or the cosmetic liquid system has a problem that appearance changes such as turbidity, precipitation, and coloring.
これまで、トコフェロールリン酸エステル及び／又はその塩に対して他の成分を配合することにより、皮膚外用剤を安定化する種々の方法が提案されている。
たとえば特許文献１では、トコフェロールリン酸エステル及び／又はその塩の水溶液を安定化する方法として、非イオン性界面活性剤を配合する方法が開示されている。該方法によれば、中性のｐＨ域においても濁りを抑制できるとされ、中でも非イオン性界面活性剤としては、ポリオキシエチレンの高級脂肪酸エステルやアルキレンエーテルが好ましいとしている。
特許文献２では、トコフェロールリン酸エステル及び／又はその塩を含有する皮膚外用剤を安定化する方法として、多価アルコールおよび／または酸および／またはその塩を配合する方法が開示されている。該方法によれば、皮膚外用剤の経時的な安定性が得られるとされている。
So far, various methods for stabilizing an external preparation for skin by blending other components with tocopherol phosphate and / or its salt have been proposed.
For example, Patent Document 1 discloses a method of blending a nonionic surfactant as a method of stabilizing an aqueous solution of a tocopherol phosphate ester and / or a salt thereof. According to this method, it is said that turbidity can be suppressed even in a neutral pH range, and among them, higher fatty acid esters and alkylene ethers of polyoxyethylene are preferred as nonionic surfactants.
Patent Document 2 discloses a method of blending a polyhydric alcohol and / or an acid and / or a salt thereof as a method for stabilizing an external preparation for skin containing a tocopherol phosphate ester and / or a salt thereof. According to this method, it is said that the stability over time of the external preparation for skin can be obtained.
しかしいずれの方法も十分な製剤安定性が得られるとは言い難く、このような背景の元、トコフェロールリン酸エステル及び／又はその塩を含有し、かつ製剤安定性に優れ、経時的な濁りや着色が抑制され、感触にも優れた皮膚外用剤の創生がなお強く求められている。 However, it is difficult to say that either method can provide sufficient formulation stability. Under such circumstances, it contains a tocopherol phosphate ester and / or a salt thereof, and has excellent formulation stability. There is still a strong demand for the creation of an external preparation for skin that is suppressed in coloring and excellent in touch.
本発明は、上記事情に鑑みてなされたものであり、トコフェロールリン酸エステル及び／又はその塩を含有し、かつ製剤安定性に優れた皮膚外用剤を提供することを目的とする。 This invention is made | formed in view of the said situation, and it aims at providing the skin external preparation which was tocopherol phosphate ester and / or its salt, and was excellent in formulation stability.
本発明者らは、上記課題を解決すべく鋭意研究した結果、トコフェロールリン酸エステル及び／又はその塩に特定のノニオン界面活性剤を組み合わせることによって上記の課題が達成されることを見出し、本発明を完成するに至った。
本発明は、以下の態様を有する。
As a result of intensive studies to solve the above problems, the present inventors have found that the above problems can be achieved by combining a specific nonionic surfactant with a tocopherol phosphate ester and / or a salt thereof. It came to complete.
The present invention has the following aspects.
［１］トコフェロールリン酸エステル及び／又はその塩と、下記一般式（１）で表されるノニオン界面活性剤（１）と、キレート剤と、を含有し、前記キレート剤が、ジエチレントリアミン五酢酸及びその塩、Ｌ−グルタミン酸二酢酸及びその塩、並びに、エチレンジアミンテトラ（メチレンホスホン酸）及びその塩からなる群から選ばれる１または２以上のキレート剤である皮膚外用剤。 [1] A tocopherol phosphate ester and / or a salt thereof, a nonionic surfactant (1) represented by the following general formula (1), and a chelating agent , wherein the chelating agent comprises diethylenetriaminepentaacetic acid and A skin external preparation which is one or more chelating agents selected from the group consisting of salts thereof, L-glutamic acid diacetic acid and salts thereof, and ethylenediaminetetra (methylenephosphonic acid) and salts thereof .
［式中、ａ、ｂ、ｃはそれぞれ正の整数である。］
［２］前記一般式（１）中のａ＋ｃの平均値が４〜４００であり、かつｂの平均値が５〜７０である、［１］に記載の皮膚外用剤。
［３］前記トコフェロールリン酸エステルの塩が、アルカリ金属の塩である、［１］又は［２］に記載の皮膚外用剤。
［４］前記アルカリ金属が、ナトリウムである、［３］に記載の皮膚外用剤。
［５］前記ノニオン性界面活性剤（１）の含有量が、０．１〜１０質量％である、［１］〜［４］のいずれか一つに記載の皮膚外用剤。
［６］前記トコフェロールリン酸エステル及び／又はその塩の含有量が、０．０１〜１０質量％である、［１］〜［５］のいずれか一つに記載の皮膚外用剤。
［７］ｐＨが６．０〜８．５である、［１］〜［６］のいずれか一つに記載の皮膚外用剤。
［８］化粧料である、請求項１〜［７］のいずれか一つに記載の皮膚外用剤。
[Wherein, a, b and c are each a positive integer. ]
[ 2 ] The skin external preparation according to [ 1 ], wherein the average value of a + c in the general formula (1) is 4 to 400, and the average value of b is 5 to 70.
[ 3 ] The external preparation for skin according to [1] or [2] , wherein the salt of the tocopherol phosphate is an alkali metal salt.
[ 4 ] The external preparation for skin according to [ 3 ], wherein the alkali metal is sodium.
[ 5 ] The skin external preparation according to any one of [1] to [ 4 ], wherein the content of the nonionic surfactant (1) is 0.1 to 10% by mass.
[ 6 ] The skin external preparation according to any one of [1] to [ 5 ], wherein the content of the tocopherol phosphate and / or salt thereof is 0.01 to 10% by mass.
[ 7 ] The external preparation for skin according to any one of [1] to [ 6 ], wherein the pH is 6.0 to 8.5.
[ 8 ] The external preparation for skin according to any one of claims 1 to [ 7] , which is a cosmetic.
本発明によれば、トコフェロールリン酸エステル及び／又はその塩を含有し、かつ製剤安定性に優れた皮膚外用剤を提供できる。 ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation which contains tocopherol phosphate ester and / or its salt, and was excellent in formulation stability can be provided.
＜トコフェロールリン酸エステル及び／又はその塩＞
本発明には、下記式（２）（式中、Ｒ1、Ｒ2及びＲ3は、互いに独立に、水素原子又はメチル基を表わす。）で示されるトコフェロールリン酸エステル及び／又はその塩が使用できる。
<Tocopherol phosphate ester and / or salt thereof>
In the present invention, a tocopherol phosphate ester and / or a salt thereof represented by the following formula (2) (wherein R 1 , R 2 and R 3 independently represent a hydrogen atom or a methyl group) Can be used.
上記式（２）で示される、トコフェロールリン酸エステルのうちでは、Ｒ1、Ｒ2およびＲ3がすべてメチル基である、α−トコフェロール；Ｒ1、Ｒ3がメチル基であり、Ｒ2が水素原子である、β−トコフェロール；Ｒ1およびＲ2がメチル基であり、Ｒ3が水素原子である、γ−トコフェロール；Ｒ1がメチル基であり、Ｒ2およびＲ3が水素原子である、δ−トコフェロール；の各々のリン酸エステルが最も一般的である。中でも、α体およびγ体が好ましく用いられる。 Among the tocopherol phosphates represented by the above formula (2), R 1 , R 2 and R 3 are all methyl groups, α-tocopherol; R 1 and R 3 are methyl groups, and R 2 is Β-tocopherol that is a hydrogen atom; R 1 and R 2 are methyl groups, R 3 is a hydrogen atom, γ-tocopherol; R 1 is a methyl group, and R 2 and R 3 are hydrogen atoms , Δ-tocopherol; each of which is the most common. Of these, α-form and γ-form are preferably used.
なお、上記式（２）で示される、トコフェロールリン酸エステルは、クロマン環の２位に不斉炭素原子を有するので、ｄ体、ｌ体の立体異性体、ｄｌ体が存在するが、本発明はこれらの異性体の何れをも含む。 In addition, since the tocopherol phosphate represented by the above formula (2) has an asymmetric carbon atom at the 2-position of the chroman ring, there are d-form, l-form stereoisomer, and dl-form. Includes any of these isomers.
前記トコフェロールリン酸エステルの塩として、好ましいものを挙げれば、トコフェロールリン酸エステルの、ナトリウム塩、カリウム塩などのアルカリ金属塩；マグネシウム塩、カルシウム塩などのアルカリ土類金属塩；アンモニウム塩、アルキルアンモニウム塩、亜鉛塩などが挙げられる。 Preferred examples of the tocopherol phosphate salt include alkali metal salts such as sodium salt and potassium salt of tocopherol phosphate ester; alkaline earth metal salts such as magnesium salt and calcium salt; ammonium salt and alkylammonium salt. Examples include salts and zinc salts.
これらのうち、トコフェロールリン酸エステルの、アルカリ金属塩、とくにナトリウム塩は、水への溶解性が高く、また性状が粉末となるため取り扱いが容易になるという利点を有しており、特に好ましい。
トコフェロールリン酸エステル及び／又はその塩としては、１種を単独で用いても２種以上を併用してもよい。
トコフェロールリン酸エステル及び／又はその塩の配合量は、皮膚外用剤全量中、０．０１〜１０質量％が好ましく、０．５〜５質量％がより好ましい。０．０１質量％以上であると、本発明の皮膚外用剤を皮膚に適用した際に、トコフェロールリン酸エステル及び／又はその塩の皮膚への移行が速やかであり、皮膚外用剤に求められる効能効果が充分に発揮される。１０質量％を超えて配合しても、さらに高い効果が得られるとは限らないので、経済的ではない。
Of these, alkali metal salts, particularly sodium salts, of tocopherol phosphates are particularly preferred because they have the advantages of high solubility in water and ease of handling because of their powder properties.
As the tocopherol phosphate and / or salt thereof, one kind may be used alone, or two or more kinds may be used in combination.
0.01-10 mass% is preferable in the skin external preparation whole quantity, and, as for the compounding quantity of a tocopherol phosphate ester and / or its salt, 0.5-5 mass% is more preferable. When it is 0.01% by mass or more, when the external preparation for skin of the present invention is applied to the skin, the tocopherol phosphate and / or its salt are rapidly transferred to the skin, and the efficacy required for the external preparation for skin The effect is fully demonstrated. Even if it exceeds 10% by mass, a higher effect is not always obtained, so it is not economical.
＜ノニオン界面活性剤（１）＞
本発明の皮膚外用剤は、トコフェロールリン酸エステル及び／又はその塩とともに、下記一般式（１）で表さるノニオン界面活性剤（１）を含有する。
<Nonionic surfactant (1)>
The skin external preparation of this invention contains the nonionic surfactant (1) represented by following General formula (1) with tocopherol phosphate ester and / or its salt.
ノニオン界面活性剤（１）は、ポリオキシエチレン（ＰＯＥ）鎖の間にポリオキシプロピレン（ＰＯＰ）鎖がエーテル結合したＰＯＥ−ＰＯＰ−ＰＯＥブロック共重合体の構造（以下、ＰＯＥ−ＰＯＰ−ＰＯＥ型ということがある。）をとるＰＯＥ・ＰＯＰグリコールである。
Nonionic surfactant (1) has a structure of a POE-POP-POE block copolymer in which polyoxypropylene (POP) chains are ether-bonded between polyoxyethylene (POE) chains (hereinafter referred to as POE-POP-POE type). POE / POP glycol.
前記一般式（１）中、ａは、ＰＯＥ鎖（ＣＨ２ＣＨ２Ｏ）ａを構成するオキシエチレン基の数（重合度）を示す。ｂはＰＯＰ鎖（ＣＨ（ＣＨ３）ＣＨ２Ｏ）ｂを構成するオキシプロピレン基の数（重合度）を示す。ｃはＰＯＥ鎖（ＣＨ２ＣＨ２Ｏ）ｃを構成するオキシエチレン基の数（重合度）を示す。
ノニオン界面活性剤（１）において、ａ＋ｃの平均値、すなわちノニオン界面活性剤（１）１分子あたりのオキシエチレン基の数（平均重合度）は、４〜４００が好ましく、２０〜１６０がより好ましい。また、ｂの平均値、すなわちノニオン界面活性剤（１）１分子あたりのオキシプロピレン基の数（平均重合度）は、５〜７０が好ましく、２０〜５０がより好ましい。
ノニオン界面活性剤（１）がＰＯＥ−ＰＯＰ−ＰＯＥ型であり、かつａ＋ｃおよびｂの値がそれぞれ上記範囲内であることで、皮膚外用剤の製剤安定性が充分に得られる。
ａ＋ｂ＋ｃの平均値、すなわちノニオン界面活性剤（１）１分子あたりのオキシプロピレン基およびオキシエチレン基の合計数は、９〜４７０が好ましく、３０〜３６０がより好ましい。
上記ａ、ｂ、ｃの値は、分子量またはＮＭＲ等の分析結果より求めることができる。
（ａ＋ｃ）／ｂ比は、０．０５〜８０が好ましく、０．１〜６がより好ましい。
In the general formula (1), a represents the number of oxyethylene groups (degree of polymerization) constituting the POE chain (CH 2 CH 2 O) a . b represents the number (degree of polymerization) of oxypropylene groups constituting the POP chain (CH (CH 3 ) CH 2 O) b . c is a number (polymerization degree) of oxyethylene groups constituting the POE chain (CH 2 CH 2 O) c .
In the nonionic surfactant (1), the average value of a + c, that is, the number of oxyethylene groups (average degree of polymerization) per molecule of the nonionic surfactant (1) is preferably 4 to 400, and more preferably 20 to 160. . Moreover, 5-70 are preferable and, as for the average value of b, ie, the number of oxypropylene groups (average polymerization degree) per molecule of nonionic surfactant (1), 20-50 are more preferable.
When the nonionic surfactant (1) is of the POE-POP-POE type and the values of a + c and b are within the above ranges, the preparation stability of the external preparation for skin can be sufficiently obtained.
The average value of a + b + c, that is, the total number of oxypropylene groups and oxyethylene groups per molecule of the nonionic surfactant (1) is preferably 9 to 470, more preferably 30 to 360.
The values of a, b, and c can be obtained from the analysis results such as molecular weight or NMR.
The (a + c) / b ratio is preferably 0.05 to 80, and more preferably 0.1 to 6.
ノニオン界面活性剤（１）として具体的には、ＰＯＥ（５）ＰＯＰ（５）グリコール、ＰＯＥ（５）ＰＯＰ（３０）グリコール、ＰＯＥ（１０）ＰＯＰ（８）グリコール、ＰＯＥ（１６）ＰＯＰ（１７）グリコール、ＰＯＥ（２０）ＰＯＰ（２０）グリコール、ＰＯＥ（２５）ＰＯＰ（３０）グリコール、ＰＯＥ（３５）ＰＯＰ（４０）グリコール、ＰＯＥ（１００）ＰＯＰ（４０）グリコール、ＰＯＥ（３００）ＰＯＰ（５５）グリコール、ＰＯＥ（４００）ＰＯＰ（７０）グリコールなどが挙げられるが、これらに限定されるものではない。これらの中では、ＰＯＥ（２５）ＰＯＰ（３０）グリコール、ＰＯＥ（３５）ＰＯＰ（４０）グリコールが、前記皮膚外用剤の製剤安定性の観点からより好ましい。
なお、上記はいずれもＰＯＥ−ＰＯＰ−ＰＯＥ型のＰＯＥ・ＰＯＰグリコールである。
ＰＯＥの後の括弧内の数値は、ＰＯＥ鎖の平均重合度（すなわち前記式（１）中のａ＋ｃの平均値）を示す。ＰＯＰの後の括弧内の数値は、ＰＯＰ鎖の平均重合度（すなわち前記式（１）中のｂの平均値）を示す。
ノニオン界面活性剤（１）は、公知の製造方法により製造してもよく、市販品を用いても良い。市販品としては、例えば、（株）アデカ製の商品名「アデカプルロニックＬ」シリーズ、「アデカプルロニックＰ」シリーズ、「アデカプルロニックＦ」シリーズ、三洋化成工業（株）製の商品名「ニューポールＰＥ」シリーズなどが挙げられる。
Specific examples of the nonionic surfactant (1) include POE (5) POP (5) glycol, POE (5) POP (30) glycol, POE (10) POP (8) glycol, POE (16) POP (17). ) Glycol, POE (20) POP (20) glycol, POE (25) POP (30) glycol, POE (35) POP (40) glycol, POE (100) POP (40) glycol, POE (300) POP (55) ) Glycol, POE (400) POP (70) glycol and the like, but are not limited thereto. Among these, POE (25) POP (30) glycol and POE (35) POP (40) glycol are more preferable from the viewpoint of the formulation stability of the external preparation for skin.
All of the above are POE-POP-POE type POE / POP glycols.
The numerical value in parentheses after POE indicates the average degree of polymerization of the POE chain (that is, the average value of a + c in the formula (1)). The numerical value in parentheses after POP indicates the average degree of polymerization of the POP chain (that is, the average value of b in the formula (1)).
The nonionic surfactant (1) may be produced by a known production method, or a commercially available product may be used. Commercially available products include, for example, trade names “Adeka Pluronic L” series, “Adeka Pluronic P” series, “Adeka Pluronic F” series manufactured by Adeka Co., Ltd., “New Pole PE” manufactured by Sanyo Chemical Industries, Ltd. ”Series.
ノニオン界面活性剤（１）は、１種を単独で用いても２種以上を併用してもよい。
ノニオン界面活性剤（１）の含有量は、皮膚外用剤全量中、０．１〜１０質量％が好ましく、０．５〜５質量％がより好ましい。０．１質量％以上であると、製剤の安定性に優れ、保存時の沈殿や濁りが生じにくい。１０質量％を超えて配合しても、さらに高い効果が得られるとは限らないので、経済的ではない。
Nonionic surfactant (1) may be used individually by 1 type, or may use 2 or more types together.
As for content of nonionic surfactant (1), 0.1-10 mass% is preferable in the skin external preparation whole quantity, and 0.5-5 mass% is more preferable. When the content is 0.1% by mass or more, the stability of the preparation is excellent, and precipitation and turbidity during storage are less likely to occur. Even if it exceeds 10% by mass, a higher effect is not always obtained, so it is not economical.
＜キレート剤＞
本発明の皮膚外用剤においては、トコフェロールリン酸エステル及び/又はその塩と、ノニオン系界面活性剤（１）のほか、更にキレート剤を含むことが好ましい。これにより、製剤の着色防止および濁りの発生防止の効果が、更に顕著になるものである。原因は定かではないが、恐らくはキレート剤が製剤中の微量金属をトラップすることによる影響であると考えられる。
本願発明におけるキレート剤としては、キレート能を有していれば特に限定されるものではない。具体的なキレート剤としては、アミノカルボン酸系キレート剤、ホスホン酸系キレート剤等が挙げられ、これらを１種又は２種以上を組み合わせて用いることができる。用途の面から考慮して、エチレンジアミン四酢酸及びその塩、ジエチレントリアミン五酢酸及びその塩、ヒドロキシエチルエチレンジアミン三酢酸及びその塩、ヒドロキシエチリデンジホスホン酸及びその塩、エチレンジアミンテトラ（メチレンホスホン酸）及びその塩、ジカルボキシメチルグルタミン酸及びその塩、がより好ましい。
キレートの塩としては、Ｎａ、Ｋ等のアルカリ金属塩、アンモニウム塩等が挙げられるが、Ｎａ塩がより好ましい。本願発明におけるキレート剤の添加量は、製造条件や使用する原料にもよるが、組成物全量に対してキレート剤を０．０１〜５．０質量％含有していることが好ましく、一般的な製造条件下で混入する可能性がある微量金属量を勘案すると、より好ましいのは０．０２〜２．０質量％である。キレート剤の添加量が０．０１質量％以下の場合は、着色及び濁りを完全に抑制することができない場合があり、また５．０質量％以上では使用感の低下等、配合量に見合った効果が得られないおそれがある。
<Chelating agent>
The external preparation for skin of the present invention preferably contains a chelating agent in addition to the tocopherol phosphate and / or salt thereof and the nonionic surfactant (1). Thereby, the effect of preventing coloring of the preparation and preventing the occurrence of turbidity becomes more remarkable. The cause is not clear, but it is probably due to the chelating agent trapping trace metals in the formulation.
The chelating agent in the present invention is not particularly limited as long as it has chelating ability. Specific chelating agents include aminocarboxylic acid chelating agents, phosphonic acid chelating agents, and the like, and these can be used alone or in combination of two or more. In view of use, ethylenediaminetetraacetic acid and its salt, diethylenetriaminepentaacetic acid and its salt, hydroxyethylethylenediaminetriacetic acid and its salt, hydroxyethylidene diphosphonic acid and its salt, ethylenediaminetetra (methylenephosphonic acid) and its salt Dicarboxymethyl glutamic acid and salts thereof are more preferable.
Examples of the chelate salt include alkali metal salts such as Na and K, ammonium salts, and the like, and Na salts are more preferable. The addition amount of the chelating agent in the present invention is preferably 0.01 to 5.0% by mass of the chelating agent with respect to the total amount of the composition, although it depends on the production conditions and the raw materials used. Considering the amount of trace metals that may be mixed under the production conditions, 0.02 to 2.0% by mass is more preferable. When the addition amount of the chelating agent is 0.01% by mass or less, coloring and turbidity may not be completely suppressed, and when it is 5.0% by mass or more, it corresponds to the blending amount such as a decrease in feeling of use. The effect may not be obtained.
＜その他の任意成分＞
本発明の皮膚外用剤は、本発明の効果を損なわない範囲で、トコフェロールおよびトコフェロールリン酸エステル及び／又はその塩以外のトコフェロール誘導体から選ばれる少なくとも１種を配合してもよい。
トコフェロールリン酸エステル及び／又はその塩以外のトコフェロール誘導体としては、トコフェロール酢酸エステル、トコフェロールコハク酸エステル、トコフェロールニコチン酸エステル、トコフェロールジメチルグリシンエステル、トコフェロールサルコシンエステル、レチノイン酸トコフェロールエステル、（アスコルビル／トコフェリル）リン酸エステル、マレイン酸アスコルビルトコフェリル等、及びその塩が挙げられる。塩としては、ナトリウム塩、カリウム塩等が挙げられる。
なお、皮膚外用剤中で、トコフェロールリン酸エステル及び／又はその塩が分解してリン酸とトコフェロールが生じることがある。そのため、本発明の皮膚外用剤には、製造時に配合していなくても、微量のトコフェロールが含まれることがある。
<Other optional components>
The skin external preparation of this invention may mix | blend at least 1 sort (s) chosen from tocopherol and tocopherol phosphates other than the tocopherol phosphate ester and / or its salt in the range which does not impair the effect of this invention.
Examples of tocopherol derivatives other than tocopherol phosphate and / or salts thereof include tocopherol acetate, tocopherol succinate, tocopherol nicotinate, tocopherol dimethylglycine ester, tocopherol sarcosine ester, retinoic acid tocopherol ester, (ascorbyl / tocopheryl) phosphorus Examples include acid esters, ascorbyl tocopheryl maleate, and the like, and salts thereof. Examples of the salt include sodium salt and potassium salt.
In addition, in a skin external preparation, a tocopherol phosphate ester and / or its salt may decompose | disassemble and a phosphoric acid and a tocopherol may arise. Therefore, the skin external preparation of the present invention may contain a trace amount of tocopherol even if it is not blended at the time of manufacture.
本発明の皮膚外用剤は、上記のほか、必要に応じて、本発明の効果を損なわない範囲で、皮膚外用剤に通常用いられる成分、たとえば皮膚外用剤として薬学的に許容され得る担体、添加剤等を含有してもよい。このような成分としては、たとえば、炭化水素類、天然油脂類、脂肪酸類、高級アルコール類、アルキルグリセリルエーテル類、エステル類、シリコーン油類、糖類、高分子類、アニオン界面活性剤、カチオン界面活性剤、両性界面活性剤、前記ノニオン界面活性剤（１）に該当しないノニオン界面活性剤、天然系界面活性剤、紫外線吸収剤、粉体類、色材類、アミノ酸類、ペプチド類、ビタミン類、ビタミン様作用因子類、防腐剤、酸化防止剤、金属イオン封鎖剤、保湿剤、抗炎症剤、ｐＨ調整剤、塩類、有機酸類、美白剤、精油類、テルペン類、香料、水等が挙げられる。 In addition to the above, the external preparation for skin of the present invention contains components usually used for external preparation for skin, for example, a pharmaceutically acceptable carrier as an external preparation for skin, as long as the effects of the present invention are not impaired. An agent or the like may be contained. Examples of such components include hydrocarbons, natural fats and oils, fatty acids, higher alcohols, alkyl glyceryl ethers, esters, silicone oils, sugars, polymers, anionic surfactants, and cationic surfactants. Agents, amphoteric surfactants, nonionic surfactants not corresponding to the above-mentioned nonionic surfactant (1), natural surfactants, ultraviolet absorbers, powders, color materials, amino acids, peptides, vitamins, Vitamin-like agents, antiseptics, antioxidants, sequestering agents, moisturizers, anti-inflammatory agents, pH adjusters, salts, organic acids, whitening agents, essential oils, terpenes, fragrances, water, etc. .
本発明の皮膚外用剤は、必要に応じて上記成分に溶媒・分散媒を加えて調整してもよい。たとえばエチレングリコール、ジエチレングリコール、ポリエチレングリコール、プロピレングリコール、ポリプロピレングリコール、グリセリン、ジグリセリン、ポリグリセリン、１，３−ブタンジオール、トリエチレングリコール、ジプロピレングリコール、３−メチル−１，３−ブタンジオール、１，２−ペンタンジオール、１，４−ペンタンジオール、１，５−ペンタンジオール、２，４−ペンタンジオール、２-メチルー２，４−ペンタンジオール、３−メチル−１，５−ペンタンジオール、１，２−ヘキサンジオール、１，６−ヘキサンジオール等の多価アルコール類、エタノール、イソプロピルアルコール、１−ブタノール、２-ブタノール、ベンジルアルコール等の一価の低級アルコール類、水などが挙げられる。 The external preparation for skin of the present invention may be adjusted by adding a solvent / dispersion medium to the above components as necessary. For example, ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 1,3-butanediol, triethylene glycol, dipropylene glycol, 3-methyl-1,3-butanediol, 1 , 2-pentanediol, 1,4-pentanediol, 1,5-pentanediol, 2,4-pentanediol, 2-methyl-2,4-pentanediol, 3-methyl-1,5-pentanediol, 1, Examples thereof include polyhydric alcohols such as 2-hexanediol and 1,6-hexanediol, monovalent lower alcohols such as ethanol, isopropyl alcohol, 1-butanol, 2-butanol and benzyl alcohol, and water.
本発明の皮膚外用剤としては、化粧料、医薬品等が挙げられる。
本発明の皮膚外用剤が化粧料である場合、さらに、既存の化粧品原料を一般的な濃度で添加することもできる。たとえば、化粧品原料基準第二版注解、日本公定書教会編、１９８４（薬事日報社）、化粧品原料基準外成分規格、厚生省薬務局審査課監修、１９９３（薬事日報社）、化粧品原料基準外成分規格追補、厚生省薬務局審査課監修、１９９３（薬事日報社）、化粧品種別許可基準、厚生省薬務局審査課監修、１９９３（薬事日報社）、化粧品種別配合成分規格、厚生省薬務局審査課監修、１９９７（薬事日報社）、および化粧品原料辞典、平成３年（日光ケミカルズ）等に記載されている全ての化粧品原料を使用することができる。
Examples of the external preparation for skin of the present invention include cosmetics and pharmaceuticals.
When the skin external preparation of the present invention is a cosmetic, an existing cosmetic raw material can be added at a general concentration. For example, Cosmetic Material Standards Second Edition Commentary, Japan Official Church Church, 1984 (Pharmaceutical Daily Report), Cosmetic Raw Material Standards Independent Component Standard, Ministry of Health and Welfare Pharmaceutical Affairs Bureau Supervision Division, 1993 (Pharmaceutical Daily Report), Cosmetic Ingredients Nonstandard Component Standards supplement, supervised by the Ministry of Health and Welfare Pharmacy Examination Division, 1993 (Pharmaceutical Daily), permission standards by cosmetic type, supervision by the Ministry of Health and Welfare Pharmacy Examination Division, 1993 (Pharmaceutical Daily), formulation standard by cosmetic variety, Ministry of Health and Welfare Pharmacy Examination Division All cosmetic raw materials described in the supervision, 1997 (Pharmaceutical Daily), cosmetic raw material dictionary, 1991 (Nikko Chemicals), etc. can be used.
本発明の皮膚外用剤の剤型としては、使用時に皮膚に接触させて用いられるものであれば特に制限はなく、用途に応じて適宜設定される。たとえばローション、乳液、クリーム、パック等に適用することが出来る。本発明の皮膚外用剤は、特に、沈殿の目立つローション製剤で効果を発揮する。
本発明の皮膚外用剤のｐＨは、６．０〜８．５であることが好ましい。ｐＨがこの範囲内であると、トコフェロールリン酸エステル及び／又はその塩の安定性が良好で、製剤安定性もより良好となる。なお該ｐＨは、約２５℃における値である
The dosage form of the external preparation for skin of the present invention is not particularly limited as long as it is used in contact with the skin at the time of use, and is appropriately set according to the use. For example, it can be applied to lotions, emulsions, creams, packs and the like. The external preparation for skin of the present invention is particularly effective in a lotion preparation with a noticeable precipitate.
The pH of the external preparation for skin of the present invention is preferably 6.0 to 8.5. When the pH is within this range, the stability of the tocopherol phosphate ester and / or its salt is good, and the formulation stability is also better. The pH is a value at about 25 ° C.
本発明の皮膚外用剤は、トコフェロールリン酸エステル及び／又はその塩、ノニオン界面活性剤（１）およびその他の任意成分を配合して製剤化することにより製造される。製剤化は、剤型に応じて、常法に従って実施できる。 The external preparation for skin of the present invention is produced by blending and formulating a tocopherol phosphate and / or a salt thereof, a nonionic surfactant (1) and other optional components. Formulation can be performed according to a conventional method according to the dosage form.
本発明では、トコフェロールリン酸エステル及び／又はその塩とノニオン界面活性剤（１）とを配合することで、理由は定かではないが、皮膚外用剤の経時的な着色や濁りの発生が抑制されている。
そのため本発明の皮膚外用剤は、化粧料や医薬品を含む皮膚外用剤全般に有用に用いることができ、中でも特に化粧料に有用である。
In the present invention, the tocopherol phosphate ester and / or salt thereof and the nonionic surfactant (1) are blended, and although the reason is not clear, the occurrence of coloring and turbidity of the skin external preparation over time is suppressed. ing.
Therefore, the skin external preparation of the present invention can be usefully used for all skin external preparations including cosmetics and pharmaceuticals, and is particularly useful for cosmetics.
以下、実施例に基づいて本発明をより具体的に説明するが、本発明はこれらの実施例に限定されるものではない。 EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example, this invention is not limited to these Examples.
〔実施例１〜１２（参考例１〜１２）、比較例１〜６〕
表１に示す組成（単位：質量％）となるように各成分を均一に分散溶解し、攪拌混合することによってローションを得た。混合の手法として、先ずトコフェリルリン酸ナトリウム・グリセリン・ペンチレングリコールをマグネチックスターラーを用いて混合し、これに精製水を加えさらに攪拌溶解したのち、表中の残りの成分を添加し混合したものである。
得られたローションについて、調製直後および６ヶ月保存後の、濁りおよび着色状況を以下の手順で評価した。保存は、ローションをガラスバイアル瓶に密閉した状態で、４℃、２５℃または４０℃に設定した恒温器中に静置することにより行った。結果を表１〜表２に併記した。
[Examples 1 to 12 (Reference Examples 1 to 12) , Comparative Examples 1 to 6]
Each component was uniformly dispersed and dissolved so as to have the composition (unit: mass%) shown in Table 1, and a lotion was obtained by stirring and mixing. As a mixing method, first, sodium tocopheryl phosphate / glycerin / pentylene glycol were mixed using a magnetic stirrer, purified water was added to this, and the mixture was further stirred and dissolved, and then the remaining components in the table were added and mixed. Is.
The obtained lotion was evaluated for turbidity and coloring immediately after preparation and after storage for 6 months according to the following procedure. Storage was performed by leaving the lotion in a thermostat set at 4 ° C., 25 ° C. or 40 ° C. with the lotion sealed in a glass vial. The results are shown in Tables 1 and 2.
［１．濁り評価方法］
目視により、下記評価基準に従い評価した。
−：濁りが全く見られない。
±：ローション製剤として許容範囲内であるが、濁りがわずかに見られる。
＋：濁りが明らかに認められる。
[1. Turbidity evaluation method]
Visual evaluation was performed according to the following evaluation criteria.
-: Turbidity is not seen at all.
±: Although it is within an acceptable range as a lotion preparation, turbidity is slightly observed.
+: Turbidity is clearly observed.
［２．着色評価方法］
目視により、下記評価基準に従い評価した。
−：着色が全く見られない。
±：ローション製剤として許容範囲内であるが、着色がわずかに見られる。
＋：着色が明らかに認められる。
[2. Coloring evaluation method]
Visual evaluation was performed according to the following evaluation criteria.
-: Coloring is not seen at all.
±: Although it is within an acceptable range as a lotion preparation, coloring is slightly observed.
+: Coloring is clearly recognized.
表１〜２の評価結果に示すとおり、ノニオン界面活性剤（１）（ＰＯＥ−ＰＯＰ−ＰＯＥ型ＰＯＥ・ＰＯＰグリコール）を配合した実施例１〜１２では、界面活性剤を配合しなかった比較例１、４、およびノニオン界面活性剤（１）以外のノニオン界面活性剤（ＰＯＰ−ＰＯＥ−ＰＯＰ型グリコール）を配合した比較例２，３，５，６に比べて、幅広い温度範囲で、経時的な濁りおよび着色が抑制され、ローションの安定性が向上していた。 As shown in the evaluation results in Tables 1 and 2, in Examples 1 to 12 in which the nonionic surfactant (1) (POE-POP-POE type POE / POP glycol) was blended, a comparative example in which the surfactant was not blended Compared with Comparative Examples 2, 3, 5, and 6 in which nonionic surfactants (POP-POE-POP type glycol) other than 1, 4 and nonionic surfactant (1) were blended, over a wide temperature range, over time Turbidity and coloring were suppressed, and the stability of the lotion was improved.
〔実施例１３〜１６（参考例１３〜１６）、比較例７〜１４〕
表３に示す組成（単位：質量％）となるように各成分を均一に分散溶解し、攪拌することによってローションを得た。
得られたローションについて、表１と同様の評価（濁り評価、着色評価）を行った。結果を表３に併記した。
[Examples 13 to 16 (Reference Examples 13 to 16) , Comparative Examples 7 to 14 ]
Each component was uniformly dispersed and dissolved so that the composition (unit: mass%) shown in Table 3 was obtained, and a lotion was obtained by stirring.
About the obtained lotion, evaluation (turbidity evaluation, coloring evaluation) similar to Table 1 was performed. The results are also shown in Table 3.
表３の評価結果に示すとおり、ＰＯＥ−ＰＯＰ−ＰＯＥトリブロック型のノニオン界面活性剤（１）を配合した実施例１３〜１６では、その他のノニオン系界面活性剤を含む系（比較例７，８，１１，１２）やアニオン系界面活性剤を含む系（比較例９・１３）やカチオン系界面活性剤を含む系（比較例１０，１４）に比べ、経時的な濁り及び着色が抑制され、ローションの安定性が向上していた。 As shown in the evaluation results of Table 3, in Examples 13 to 16 in which the POE-POP-POE triblock type nonionic surfactant (1) was blended, a system containing other nonionic surfactant (Comparative Example 7, 8,11,12) and a system containing an anionic surfactant (Comparative Examples 9 and 13) and a system containing a cationic surfactant (Comparative Examples 10 and 14), turbidity and coloring over time are suppressed. The stability of the lotion was improved.
〔実施例１７〜３２、実施例３３〜３６（参考例１７〜２０）〕
表４〜５に示す組成（単位：質量％）となるように各成分を均一に分散溶解し、攪拌することによってローションを得た。
得られたローションについて、表１と同様の評価（濁り評価、着色評価）を行った。結果を表４〜５に併記した。
[Examples 17 to 32, Examples 33 to 36 (Reference Examples 17 to 20) ]
Each component was uniformly dispersed and dissolved so as to have the composition (unit: mass%) shown in Tables 4 to 5, and a lotion was obtained by stirring.
About the obtained lotion, evaluation (turbidity evaluation, coloring evaluation) similar to Table 1 was performed. The results are shown in Tables 4-5.
表４〜５の評価結果に示すとおり、実施例１７〜３６の組成物はいずれも良好な製剤安定性を示した。中でも特に、ノニオン界面活性剤（１）にくわえてキレート剤を配合した実施例１７〜３２では、キレート剤を配合しなかった実施例３３〜３６と比べて、幅広い温度範囲で、経時的な濁り及び着色が抑制され、ローションの安定性が向上していた。 As shown in the evaluation results of Tables 4 to 5, the compositions of Examples 17 to 36 all showed good formulation stability. In particular, in Examples 17 to 32 in which a chelating agent was blended in addition to the nonionic surfactant (1), turbidity over time in a wider temperature range than in Examples 33 to 36 in which no chelating agent was blended. And coloring was suppressed, and the stability of the lotion was improved.
表１〜５に示す各成分のうち、ノニオン界面活性剤（１）、その他の界面活性剤としては、それぞれ以下のものを使用した。ａ＋ｃの値、ｂの値はそれぞれ平均値である。 Among the components shown in Tables 1 to 5, the following were used as the nonionic surfactant (1) and other surfactants. The values of a + c and b are average values.
［ノニオン界面活性剤（１）］
ＨＯ（Ｃ２Ｈ４Ｏ）ａ−（Ｃ３Ｈ６Ｏ）ｂ−（Ｃ２Ｈ４Ｏ）ｃ−Ｈ、ａ＋ｃ＝１６、ｂ＝１７：アデカ社製「アデカプルロニックＬ−３４」。
ＨＯ（Ｃ２Ｈ４Ｏ）ａ−（Ｃ３Ｈ６Ｏ）ｂ−（Ｃ２Ｈ４Ｏ）ｃ−Ｈ、ａ＋ｃ＝２０、ｂ＝２０：アデカ社製「アデカプルロニックＬ−４４」。
ＨＯ（Ｃ２Ｈ４Ｏ）ａ−（Ｃ３Ｈ６Ｏ）ｂ−（Ｃ２Ｈ４Ｏ）ｃ−Ｈ、ａ＋ｃ＝５、ｂ＝３０：アデカ社製「アデカプルロニックＬ−６１」。
ＨＯ（Ｃ２Ｈ４Ｏ）ａ−（Ｃ３Ｈ６Ｏ）ｂ−（Ｃ２Ｈ４Ｏ）ｃ−Ｈ、ａ＋ｃ＝２５、ｂ＝３０：アデカ社製「アデカプルロニックＬ−６４」。
ＨＯ（Ｃ２Ｈ４Ｏ）ａ−（Ｃ３Ｈ６Ｏ）ｂ−（Ｃ２Ｈ４Ｏ）ｃ−Ｈ、ａ＋ｃ＝３５、ｂ＝４０：アデカ社製「アデカプルロニックＰ−８４」。
ＨＯ（Ｃ２Ｈ４Ｏ）ａ−（Ｃ３Ｈ６Ｏ）ｂ−（Ｃ２Ｈ４Ｏ）ｃ−Ｈ、ａ＋ｃ＝３００、ｂ＝５５：アデカ社製「アデカプルロニックＦ−１０８」。
[Nonionic surfactant (1)]
HO (C 2 H 4 O) a - (C 3 H 6 O) b - (C 2 H 4 O) c -H, a + c = 16, b = 17: manufactured by Adeka Corporation "ADEKA PLURONIC L-34".
HO (C 2 H 4 O) a - (C 3 H 6 O) b - (C 2 H 4 O) c -H, a + c = 20, b = 20: manufactured by Adeka Corporation "ADEKA PLURONIC L-44".
HO (C 2 H 4 O) a - (C 3 H 6 O) b - (C 2 H 4 O) c -H, a + c = 5, b = 30: manufactured by Adeka Corporation "ADEKA PLURONIC L-61".
HO (C 2 H 4 O) a - (C 3 H 6 O) b - (C 2 H 4 O) c -H, a + c = 25, b = 30: manufactured by Adeka Corporation "ADEKA PLURONIC L-64".
HO (C 2 H 4 O) a - (C 3 H 6 O) b - (C 2 H 4 O) c -H, a + c = 35, b = 40: manufactured by Adeka Corporation "ADEKA PLURONIC P-84".
HO (C 2 H 4 O) a - (C 3 H 6 O) b - (C 2 H 4 O) c -H, a + c = 300, b = 55: manufactured by Adeka Corporation "ADEKA PLURONIC F-108".
［その他の界面活性剤］
ＨＯ（Ｃ３Ｈ６Ｏ）ａ−（Ｃ２Ｈ４Ｏ）ｂ−（Ｃ３Ｈ６Ｏ）ｃ−Ｈ、ａ＋ｃ＝２８、ｂ＝２０：アデカ社製「アデカプルロニック１７Ｒ−２」。
ＨＯ（Ｃ３Ｈ６Ｏ）ａ−（Ｃ２Ｈ４Ｏ）ｂ−（Ｃ３Ｈ６Ｏ）ｃ−Ｈ、ａ＋ｃ＝４２、ｂ＝１５：アデカ社製「アデカプルロニック２５Ｒ−１」。
ＰＯＥ（５０）硬化ヒマシ油：日光ケミカルズ株式会社製「ＮＩＫＫＯＬ ＨＣＯ−５０」
ＰＯＥ(２０)ＰＯＰ(４)セチルエーテル：日光ケミカルズ株式会社製「ＮＩＫＫＯＬ ＰＢＣ−３４」。
ＰＯＥ（３）ラウリルエーテル硫酸Ｎａ ２５％水溶液：花王社製「エマール２０Ｃ」。
塩化セチルトリメチルアンモニウム ３０％水溶液：花王社製「コータミン６０Ｗ」。
[Other surfactants]
HO (C 3 H 6 O) a - (C 2 H 4 O) b - (C 3 H 6 O) c -H, a + c = 28, b = 20: manufactured by Adeka Corporation "ADEKA PLURONIC 17R-2".
HO (C 3 H 6 O) a - (C 2 H 4 O) b - (C 3 H 6 O) c -H, a + c = 42, b = 15: manufactured by Adeka Corporation "ADEKA PLURONIC 25R-1".
POE (50) hydrogenated castor oil: “NIKKOL HCO-50” manufactured by Nikko Chemicals Co., Ltd.
POE (20) POP (4) cetyl ether: “NIKKOL PBC-34” manufactured by Nikko Chemicals Co., Ltd.
POE (3) Lauryl ether sulfate Na 25% aqueous solution: “Emar 20C” manufactured by Kao Corporation.
Cetyltrimethylammonium chloride 30% aqueous solution: “Coatamine 60W” manufactured by Kao Corporation.
［キレート剤］
エチレンジアミン四酢酸四ナトリウム四水塩：キレスト株式会社製「キレスト ２ＤＳ」。
ジエチレントリアミン五酢酸五ナトリウム ４０％液：キレスト株式会社製「キレスト Ｐ」。
Ｌ−グルタミン酸二酢酸・四ナトリウム ４０％液：昭和電工株式会社製「ＧＬＤＡ−４Ｎａ ４０％水溶液」。
エチレンジアミンテトラメチレンホスホン酸五ナトリウム：キレスト株式会社製「キレスト ＰＨ−５４０」。
[Chelating agent]
Ethylenediaminetetraacetic acid tetrasodium tetrahydrate: “Chillest 2DS” manufactured by Kirest Corporation.
Diethylenetriaminepentaacetic acid pentasodium 40% solution: “Kyrest P” manufactured by Kirest Corporation.
L-glutamic acid diacetic acid / tetrasodium 40% solution: “GLDA-4Na 40% aqueous solution” manufactured by Showa Denko KK
Ethylenediaminetetramethylene phosphonic acid pentasodium: “Chirest PH-540” manufactured by Kirest Corporation.
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| JPS5944375A (en) * | 1982-09-06 | 1984-03-12 | Senjiyu Seiyaku Kk | Stable aqueous solution of alpha-tocopherol phosphoric ester |
| CA1333360C (en) * | 1987-10-19 | 1994-12-06 | Andrew S. Janoff | Tocopherol-based pharmaceutical systems |
| JPH09309813A (en) * | 1996-05-22 | 1997-12-02 | Nonogawa Shoji Kk | Preparation for external use for skin |
| JPH1053515A (en) * | 1996-08-09 | 1998-02-24 | Ajinomoto Co Inc | Skin lotion |
| US6458373B1 (en) * | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| JP3950216B2 (en) * | 1997-12-26 | 2007-07-25 | 日本メナード化粧品株式会社 | Topical skin preparation |
| JPH11199465A (en) * | 1998-01-07 | 1999-07-27 | Nonogawa Shoji Kk | Skin preparation for external use |
| US5919830A (en) * | 1998-04-30 | 1999-07-06 | Gopalkrishnan; Sridhar | Stable non-aqueous blends for personal care compositions |
| DE60140141D1 (en) * | 2000-11-14 | 2009-11-19 | Vital Health Sciences Pty Ltd | Compositions comprising complexes of tocopherol phosphate derivatives |
| US20060222716A1 (en) * | 2005-04-01 | 2006-10-05 | Joseph Schwarz | Colloidal solid lipid vehicle for pharmaceutical use |
| JP2007084464A (en) * | 2005-09-21 | 2007-04-05 | Adeka Corp | Cosmetic composition |
| EP1948145A2 (en) * | 2005-10-24 | 2008-07-30 | Ciba Holding Inc. | Protection of oxidizable agents |
| WO2007104173A2 (en) * | 2006-03-10 | 2007-09-20 | Laboswiss Ag | Method for solubilizing, dispersing, and stabilizing materials, products manufactured according to said method, and use thereof |
| JP5528875B2 (en) * | 2010-03-26 | 2014-06-25 | 日本メナード化粧品株式会社 | Transparent liquid skin preparation |
| JP5662794B2 (en) * | 2010-12-21 | 2015-02-04 | 株式会社ファンケル | Water-in-oil emulsion composition |
| FR2969924B1 (en) * | 2010-12-30 | 2013-11-15 | Lvmh Rech | COMPOSITION COMPRISING A TOCOPHEROL PHOSPHATE |
| JP2012206958A (en) * | 2011-03-29 | 2012-10-25 | Sunstar Inc | Vascular endothelial function improving agent |
| JP5671394B2 (en) * | 2011-03-29 | 2015-02-18 | 株式会社ファンケル | Emulsion composition for cosmetics |
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