WO2022131080A1 - Emulsified composition for external use - Google Patents
Emulsified composition for external use Download PDFInfo
- Publication number
- WO2022131080A1 WO2022131080A1 PCT/JP2021/044975 JP2021044975W WO2022131080A1 WO 2022131080 A1 WO2022131080 A1 WO 2022131080A1 JP 2021044975 W JP2021044975 W JP 2021044975W WO 2022131080 A1 WO2022131080 A1 WO 2022131080A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- external
- urea
- emulsified composition
- fatty acid
- component
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 94
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims abstract description 65
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 62
- 239000004202 carbamide Substances 0.000 claims abstract description 61
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229960004889 salicylic acid Drugs 0.000 claims abstract description 32
- 239000004094 surface-active agent Substances 0.000 claims abstract description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 21
- 229940121363 anti-inflammatory agent Drugs 0.000 claims abstract description 19
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 150000004671 saturated fatty acids Chemical class 0.000 claims abstract description 12
- -1 sorbitan fatty acid ester Chemical class 0.000 claims description 65
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 40
- 239000000194 fatty acid Substances 0.000 claims description 40
- 229930195729 fatty acid Natural products 0.000 claims description 40
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 24
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 20
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
- 239000004359 castor oil Substances 0.000 claims description 13
- 235000019438 castor oil Nutrition 0.000 claims description 12
- 235000011187 glycerol Nutrition 0.000 claims description 12
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 12
- 239000004471 Glycine Substances 0.000 claims description 10
- 238000004945 emulsification Methods 0.000 claims description 10
- 238000003860 storage Methods 0.000 abstract description 28
- 238000005191 phase separation Methods 0.000 abstract description 21
- 238000000354 decomposition reaction Methods 0.000 abstract description 19
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 18
- 229920001214 Polysorbate 60 Polymers 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 8
- 102000011782 Keratins Human genes 0.000 description 8
- 108010076876 Keratins Proteins 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 8
- 150000005215 alkyl ethers Chemical class 0.000 description 7
- 150000004665 fatty acids Chemical class 0.000 description 7
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 6
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 150000002430 hydrocarbons Chemical class 0.000 description 6
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 6
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical class COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 6
- 150000005846 sugar alcohols Polymers 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000001587 sorbitan monostearate Substances 0.000 description 5
- 235000011076 sorbitan monostearate Nutrition 0.000 description 5
- 229940035048 sorbitan monostearate Drugs 0.000 description 5
- ASKIVFGGGGIGKH-UHFFFAOYSA-N 2,3-dihydroxypropyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(O)CO ASKIVFGGGGIGKH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 235000021314 Palmitic acid Nutrition 0.000 description 4
- 235000021355 Stearic acid Nutrition 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 4
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 4
- 239000002736 nonionic surfactant Substances 0.000 description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
- 239000008117 stearic acid Substances 0.000 description 4
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 4
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 3
- LVYLCBNXHHHPSB-UHFFFAOYSA-N 2-hydroxyethyl salicylate Chemical compound OCCOC(=O)C1=CC=CC=C1O LVYLCBNXHHHPSB-UHFFFAOYSA-N 0.000 description 3
- 235000021357 Behenic acid Nutrition 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- GYCKQBWUSACYIF-UHFFFAOYSA-N Ethyl salicylate Chemical class CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 3
- IJCWFDPJFXGQBN-RYNSOKOISA-N [(2R)-2-[(2R,3R,4S)-4-hydroxy-3-octadecanoyloxyoxolan-2-yl]-2-octadecanoyloxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-RYNSOKOISA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 229940116226 behenic acid Drugs 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940005667 ethyl salicylate Drugs 0.000 description 3
- 229940075507 glyceryl monostearate Drugs 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229960001047 methyl salicylate Drugs 0.000 description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- DCBSHORRWZKAKO-UHFFFAOYSA-N rac-1-monomyristoylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(O)CO DCBSHORRWZKAKO-UHFFFAOYSA-N 0.000 description 3
- 235000003441 saturated fatty acids Nutrition 0.000 description 3
- 239000001589 sorbitan tristearate Substances 0.000 description 3
- 235000011078 sorbitan tristearate Nutrition 0.000 description 3
- 229960004129 sorbitan tristearate Drugs 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- PAFJZWHXMSQJKV-UQZRNVAESA-N (3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol;octadecanoic acid Chemical compound OC[C@@H](O)C1OC[C@H](O)[C@H]1O.OC[C@@H](O)C1OC[C@H](O)[C@H]1O.OC[C@@H](O)C1OC[C@H](O)[C@H]1O.CCCCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O PAFJZWHXMSQJKV-UQZRNVAESA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 229940082500 cetostearyl alcohol Drugs 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229960002389 glycol salicylate Drugs 0.000 description 2
- BTFJIXJJCSYFAL-UHFFFAOYSA-N icosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000007721 medicinal effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000003020 moisturizing effect Effects 0.000 description 2
- UTOPWMOLSKOLTQ-UHFFFAOYSA-N octacosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCC(O)=O UTOPWMOLSKOLTQ-UHFFFAOYSA-N 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- ZQBAKBUEJOMQEX-UHFFFAOYSA-N phenyl salicylate Chemical compound OC1=CC=CC=C1C(=O)OC1=CC=CC=C1 ZQBAKBUEJOMQEX-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 229940058287 salicylic acid derivative anticestodals Drugs 0.000 description 2
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 2
- REZQBEBOWJAQKS-UHFFFAOYSA-N triacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO REZQBEBOWJAQKS-UHFFFAOYSA-N 0.000 description 2
- DRAWQKGUORNASA-UHFFFAOYSA-N (2-hydroxy-3-octadec-9-enoyloxypropyl) octadec-9-enoate Chemical compound CCCCCCCCC=CCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCC=CCCCCCCCC DRAWQKGUORNASA-UHFFFAOYSA-N 0.000 description 1
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- PDHSAQOQVUXZGQ-JKSUJKDBSA-N (2r,3s)-2-(3,4-dihydroxyphenyl)-3-methoxy-3,4-dihydro-2h-chromene-5,7-diol Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2OC)=CC=C(O)C(O)=C1 PDHSAQOQVUXZGQ-JKSUJKDBSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- NWGAAWUUGRXXSC-UHFFFAOYSA-N 1-(2-hydroxypropoxy)propan-2-yl 2-hydroxybenzoate Chemical compound CC(O)COCC(C)OC(=O)C1=CC=CC=C1O NWGAAWUUGRXXSC-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- XDZMPRGFOOFSBL-UHFFFAOYSA-N 2-ethoxybenzoic acid Chemical compound CCOC1=CC=CC=C1C(O)=O XDZMPRGFOOFSBL-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 1
- HCJMNOSIAGSZBM-UHFFFAOYSA-N 6-methylsalicylic acid Chemical compound CC1=CC=CC(O)=C1C(O)=O HCJMNOSIAGSZBM-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- CMPDPBDUZTUXAD-UHFFFAOYSA-N [3-hydroxy-2-(16-methylheptadecanoyloxy)propyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCC(C)C CMPDPBDUZTUXAD-UHFFFAOYSA-N 0.000 description 1
- OYCUCVYCOQBTLP-UHFFFAOYSA-J [Ti+4].[O-]C(=O)c1ccccc1[O-].[O-]C(=O)c1ccccc1[O-] Chemical compound [Ti+4].[O-]C(=O)c1ccccc1[O-].[O-]C(=O)c1ccccc1[O-] OYCUCVYCOQBTLP-UHFFFAOYSA-J 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000002199 base oil Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 229960000735 docosanol Drugs 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960000514 ethenzamide Drugs 0.000 description 1
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229920006007 hydrogenated polyisobutylene Polymers 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229960000969 phenyl salicylate Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940100515 sorbitan Drugs 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001570 sorbitan monopalmitate Substances 0.000 description 1
- 229940031953 sorbitan monopalmitate Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000004711 α-olefin Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/42—Amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- the present invention relates to an external emulsified composition containing urea and a salicylic acid-based anti-inflammatory agent and capable of suppressing phase separation and urea decomposition during storage.
- Urea has a water retention effect by forming a hydrogen bond with water in the keratin and an effect of removing or softening unnecessary keratin due to protein denaturation, and is used in external compositions.
- urea is easily hydrolyzed in the external composition, it is necessary to stabilize the urea in the external composition containing urea. Therefore, various studies have been made on the formulation of an external composition capable of stabilizing urea.
- Patent Document 1 discloses that urea can be stabilized by blending a neutral amino acid such as glycine in an external composition containing urea.
- Patent Document 2 discloses that the external composition can be provided with excellent pharmaceutical stability by containing 10 to 25% by weight of urea and retinol or a derivative thereof.
- salicylic acid salicylic acid, salicylic acid derivatives, and salicylic acid-based anti-inflammatory agents such as salts thereof are used in external compositions for anti-inflammatory and analgesic applications.
- the emulsified preparation is widely used in the field of external composition because it can contain an aqueous component and an oily component, can be used for various preparation formulations, and has an excellent usability when applied to the skin.
- the present inventor has conducted various studies to develop an external emulsified composition containing urea and a salicylic acid anti-inflammatory agent, and found that the external emulsified composition containing urea and a salicylic acid anti-inflammatory agent is preserved. It was found that there was a problem in terms of storage stability due to phase separation and decomposition of urea.
- an object of the present invention to provide an external emulsified composition containing urea and a salicylic acid-based anti-inflammatory agent and capable of suppressing phase separation and urea decomposition during storage.
- the present inventor has conducted an external application containing a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof and an oil-based surfactant in addition to urea and a salicylic acid-based anti-inflammatory agent. It has been found that the emulsified composition can suppress the phase separation and the decomposition of urea by storage and can have excellent storage stability.
- the present invention has been completed by further studies based on such findings.
- Item 1 An external emulsified composition comprising (A) urea, (B) a salicylic acid-based anti-inflammatory agent, (C) a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof, and (D) a lipophilic surfactant.
- Item 2. Item 2. The external emulsification composition according to Item 1, wherein the component (D) is at least one selected from the group consisting of a sorbitan fatty acid ester, a glycerin fatty acid ester, and a polyoxyethylene hydrogenated castor oil.
- Item 3. Item 2. The external emulsified composition according to Item 1 or 2, which does not contain glycine.
- the external emulsification composition of the present invention although it contains urea and a salicylic acid-based anti-inflammatory agent, phase separation and decomposition of urea due to storage can be suppressed, and excellent storage stability can be provided.
- the external emulsified composition of the present invention comprises (A) urea, (B) a salicylic acid-based anti-inflammatory agent, (C) a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof, and (D) a lipophilic surfactant. It is characterized by containing an activator.
- urea urea
- salicylic acid-based anti-inflammatory agent a salicylic acid-based anti-inflammatory agent
- C a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof
- D a lipophilic surfactant. It is characterized by containing an activator.
- the external emulsified composition of the present invention contains urea (sometimes referred to as component (A)).
- Urea is a known component known to have a water retention action in the keratin, an unnecessary keratin removal or softening action, and the like.
- the content of the component (A) in the external emulsified composition of the present invention may be appropriately set according to the medicinal effect to be imparted, the intended use of the external emulsified composition, etc., and is, for example, 1 to 30% by weight, preferably 1 to 30% by weight. 5 to 25% by weight, more preferably 10 to 20% by weight.
- the external emulsified composition of the present invention contains a salicylic acid-based anti-inflammatory agent (sometimes referred to as a component (B)).
- salicylic acid-based anti-inflammatory agent examples include salicylic acid, salicylic acid derivatives, and salts thereof.
- derivative of salicylic acid examples include acetylsalicylic acid (aspirin), salicylic acid (ethenzamid), sulfosalicylic acid, methyl salicylic acid, ethyl salicylic acid, glycol salicylate, ethylene glycol salicylate, dipropylene glycol salicylate, titanium salicylate, 2-ethylhexyl salicylate, and salicylic acid. Examples thereof include homomentyl and phenyl salicylate.
- salts of salicylic acid and its derivatives examples include alkali metal salts such as sodium and potassium; and alkaline earth metal salts such as magnesium.
- salicylic acid-based anti-inflammatory agents may be used alone or in combination of two or more.
- salicylic acid-based anti-inflammatory agents salicylic acid, salts of salicylic acid, ethyl salicylate, methyl salicylate, and more preferably salicylic acid can be mentioned.
- the content of the component (B) in the external emulsified composition of the present invention may be appropriately set according to the medicinal effect to be imparted, the intended use of the external emulsified composition, etc., but for example, the total amount of the component (B) is 0. 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight, and more preferably 0.1 to 0.5% by weight.
- the ratio of the component (A) to the component (B) is not particularly limited, but for example, the total amount of the component (B) is 0.
- examples thereof include 01 to 300 parts by weight, preferably 0.05 to 100 parts by weight, and more preferably 0.1 to 50 parts by weight.
- the external emulsified composition of the present invention contains a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof (sometimes referred to as a component (C)).
- the saturated fatty acid and / or a salt thereof may have 14 or more carbon atoms, but is preferably 14 to 30 carbon atoms, more preferably, from the viewpoint of more effectively suppressing phase separation and urea decomposition during storage. 14 to 24 carbon atoms, more preferably 14 to 22 carbon atoms, and particularly preferably 18 carbon atoms.
- Saturated fatty acids more specifically, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoseric acid, cellotic acid, montanic acid, melicic acid; preferably myristic acid, palmitic acid, stearic acid, arachidic acid.
- Bechenic acid, lignoseric acid more preferably myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid; more preferably stealic acid.
- Examples of the salt of saturated fatty acid having 14 or more carbon atoms include alkali metal salts such as sodium salt and potassium salt.
- component (C) one may be selected and used from among saturated fatty acids having 14 or more carbon atoms and salts thereof, or two or more thereof may be used in combination. good.
- the content of the component (C) in the external emulsified composition of the present invention is not particularly limited, but for example, the total amount of the component (C) is 0.01 to 10% by weight, preferably 0.1 to 6% by weight. More preferably, 1 to 6% by weight is mentioned.
- the ratio of the component (A) to the component (C) is not particularly limited, but for example, the total amount of the component (C) is 0.
- examples thereof include 1 to 1200 parts by weight, preferably 0.1 to 100 parts by weight, and more preferably 0.1 to 50 parts by weight.
- the external emulsified composition of the present invention contains a lipophilic surfactant (sometimes referred to as component (D)).
- the lipophilic surfactant is a surfactant having a property of having a higher affinity for an oil agent than an affinity for water.
- specific examples of the lipophilic surfactant include nonionic surfactants having an HLB value of 8 or less, preferably an HLB value of 1 to 8, and more preferably an HLB value of 2 to 6.5.
- Examples of the carbon number of the fatty acid constituting the sorbitan fatty acid ester include 10 to 22, preferably 14 to 22, and more preferably 16 to 20.
- Examples of the number of fatty acids bound per molecule of the sorbitan fatty acid ester include 1 to 4, preferably 1 to 3.
- Specific examples of the sorbitan fatty acid ester include sorbitan monooleate, sorbitan monostearate, sorbitan sesquioleate, sorbitan coconut oil fatty acid, sorbitan monopalmitate, sorbitan tristearate, and sorbitan trioleate.
- sorbitan monostearate, sorbitan sesquistearate, sorbitan tristearate, and more preferably sorbitan monostearate are mentioned.
- Examples of the carbon number of the fatty acid constituting the glycerin fatty acid ester include 10 to 22, preferably 14 to 22, and more preferably 16 to 20.
- the number of fatty acids bound to one molecule of the glycerin fatty acid is not particularly limited, and examples thereof include 1 to 3, preferably 1 or 2, and more preferably 1.
- Specific examples of the glycerin fatty acid ester include glyceryl monomyristate, glyceryl monostearate, glyceryl monoisostearate, glyceryl monooleate, glyceryl dimyristate, glyceryl distearate, glyceryl diisostearate, and glyceryl dioleate. Be done. Among these glycerin fatty acid esters, glyceryl monostearate and glyceryl monomyristate are preferable.
- lipophilic surfactants may be used alone or in combination of two or more.
- the ratio of the component (A) to the component (D) is not particularly limited, but for example, the total amount of the component (D) is 0.
- Examples thereof include 01 to 500 parts by weight, preferably 0.05 to 200 parts by weight, and more preferably 0.1 to 50 parts by weight.
- the external emulsified composition of the present invention does not contain a neutral amino acid (an amino acid whose side chain does not contain an amino group or a carboxyl group).
- the external emulsified composition of the present invention may contain a hydrophilic surfactant, if necessary.
- the hydrophilic surfactant is a surfactant having a property of having a higher affinity for water than an affinity for an oil agent.
- Specific examples of the hydrophilic surfactant include nonionic surfactants having an HLB value of more than 8.
- hydrophilic surfactant examples include polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkyl ether, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, sorbitan fatty acid ester, and polyoxyethylene sorbit fatty acid ester.
- nonionic surfactants such as polyoxyethylene hydrogenated castor oil, polyethylene glycol fatty acid ester, and lecithin derivative, those satisfying the above HLB value can be mentioned.
- polyoxyethylene sorbitan fatty acid ester and polyoxyethylene alkyl ether are preferably mentioned from the viewpoint of more effectively suppressing phase separation and urea decomposition during storage.
- Examples of the average number of moles of ethylene oxide (EO) constituting the polyoxyethylene sorbitan fatty acid ester include 5 to 50 mol, preferably 10 to 30 mol, and more preferably 15 to 25 mol.
- Examples of the carbon number of the fatty acid constituting the polyoxyethylene sorbitan fatty acid ester include 10 to 22, preferably 14 to 22, and more preferably 16 to 20.
- Specific examples of the polyoxyethylene sorbitan fatty acid ester include monooleic acid polyoxyethylene sorbitan, trioleic acid polyoxyethylene sorbitan, tristearate polyoxyethylene sorbitan, monostearate polyoxyethylene sorbitan, and monopalmitic acid polyoxy.
- Examples of the average number of moles of ethylene oxide (EO) constituting the polyoxyethylene alkyl ether include 2 to 50 mol, preferably 5 to 30 mol, and more preferably 15 to 25 mol.
- the number of carbon atoms of the alkyl group constituting the polyoxyethylene alkyl ether is not particularly limited, and examples thereof include 10 to 24 carbon atoms, preferably 14 to 24 carbon atoms, and more preferably 16 to 24 carbon atoms.
- Specific examples of the polyoxyethylene alkyl ether include polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, and polyoxyethylene araquil ether. Among these polyoxyethylene alkyl ethers, polyoxyethylene alkyl ethers are preferable from the viewpoint of more effectively suppressing discoloration due to storage.
- the content thereof is not particularly limited, but for example, the total amount of the hydrophilic surfactant is 0.5 to 20% by weight, preferably 1. -15% by weight, more preferably 1.5-5% by weight.
- the polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include 1,3-butylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, and glycerin. Among these polyhydric alcohols, glycerin is preferable. These polyhydric alcohols may be used alone or in combination of two or more.
- the content thereof is not particularly limited, but for example, the total amount of the polyhydric alcohol is 0.1 to 30% by weight, preferably 0.5 to 20%. By weight%, more preferably 1 to 10% by weight.
- the hydrocarbon oil is not particularly limited as long as it is pharmaceutically acceptable, but for example, liquid paraffin, ⁇ -olefin oligomer, petrolatum, microcrystalline wax, gelled hydrocarbon (plastibase, etc.), hydrogenated polyisobutene, etc. Can be mentioned.
- liquid paraffin and petrolatum are preferable.
- the external emulsified composition of the present invention may contain a pharmacological component in addition to the above-mentioned components.
- pharmacological components include steroids, antihistamines, local anesthetics, anti-inflammatory agents (other than component (B)), moisturizers (other than component (A)), bactericides, antibacterial agents, antipruritic agents, and skin.
- Protective agents, blood circulation promoting ingredients, vitamins, mucopolysaccharides and the like can be mentioned.
- These pharmacological components may be used alone or in combination of two or more. When these pharmacological components are contained in the external composition of the present invention, the concentration thereof may be appropriately set according to the type of the pharmacological component used, the expected effect, and the like.
- the emulsification type of the external emulsification composition of the present invention may be either an oil-in-water type or a water-in-oil type, and an oil-in-water type is preferable.
- the formulation form of the external emulsified composition of the present invention is not particularly limited, and examples thereof include external pharmaceuticals such as creams, emulsions, lotions, liniments, and aerosols. Among these, a cream agent is preferably mentioned.
- the external emulsified composition of the present invention can be produced according to a known method for formulating an emulsified preparation, depending on the emulsified type.
- the components to be contained are divided into a water-soluble component and an oil-based component, and an aqueous phase containing the water-soluble component and an oil phase containing the oil-based component are prepared.
- Test Example 1 An external emulsified composition (creamy oil-in-water emulsified preparation) having the compositions shown in Tables 1 and 2 was prepared. Specifically, first, surfactants (sorbitan monostearate, sorbitan sesquistearate, sorbitan tristearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monostearate, polyoxyethylene hydrogenated castor oil 10, polysorbate).
- surfactants sorbitan monostearate, sorbitan sesquistearate, sorbitan tristearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monostearate, polyoxyethylene hydrogenated castor oil 10, polysorbate.
- a composition for an oil phase was prepared by mixing and heating and dissolving at 80 ° C. Separately, a predetermined amount of urea, salicylic acid, glycine, triethanolamine and water were mixed to prepare a composition for an aqueous phase. Next, the aqueous phase composition heated to 80 ° C.
- the stability of the emulsified state and the stability of urea were evaluated by the following methods.
- ⁇ Stability in emulsified state 16 g of each external emulsified composition immediately after preparation was filled in a 20 ml glass bottle and stored for 1 month under a light-shielded condition of 50 ° C. The appearance of each external emulsified composition after storage for 1 month was visually observed, and 15 points were "a state in which phase separation was not observed and the same emulsified state as immediately after preparation was maintained", and "phase separation was observed”. The degree of stability of the emulsified state was scored between 1 and 15 points, with 1 point being "a state in which the emulsified state could not be stably maintained and was not uniform even when shaken.” For reference, FIG. 1 shows the appearance of each external emulsified composition evaluated as 1 point and 15 points.
- the urea concentration in each external emulsified composition before and after storage for 2 months is quantified by HPLC, and the urea concentration before storage is set to 100%, and the residual rate (%) of urea after storage for 2 months is set to the first decimal place. The rounded value was calculated.
- an external emulsified composition in which salicylic acid in each of the external emulsified compositions of Comparative Examples 1 to 4 was changed to ethyl salicylate or methyl salicylate was prepared, and the emulsified state and the stability of urea were evaluated by the same method as in Test Example 1.
- each external emulsified composition in which salicylic acid in each of the external compositions of Examples 1 to 12 was changed to ethyl salicylate or methyl salicylate was prepared, and the emulsified state and urea stability were evaluated by the same method as in Test Example 1.
- phase separation and decomposition of urea could be suppressed to the same extent as in Examples 1 to 12 corresponding to this.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Birds (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Dispersion Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Toxicology (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
[Problem] To provide an emulsified composition for external use that comprises urea and a salicylic acid-based anti-inflammatory agent and that can suppress phase separation and decomposition of urea due to storage. [Solution] An emulsified composition for external use that comprises urea, a salicylic acid-based anti-inflammatory agent and, moreover, a saturated fatty acid having 14 or more carbon atoms and/or a salt thereof and a lipophilic surfactant. This emulsified composition for external use can suppress phase separation and decomposition of urea due to storage and exhibit high storage stability.
Description
本発明は、尿素及びサリチル酸系抗炎症剤を含み、保存による相分離及び尿素の分解を抑制できる外用乳化組成物に関する。
The present invention relates to an external emulsified composition containing urea and a salicylic acid-based anti-inflammatory agent and capable of suppressing phase separation and urea decomposition during storage.
尿素には、角質中での水分と水素結合を形成することによる水分保持作用や、タンパク質変性による不要な角質を除去したり軟化させたりする作用等があり、外用組成物に使用されている。一方、尿素は、外用組成物中で加水分解され易いため、尿素を含む外用組成物では、尿素の安定化を図ること必要になる。そこで、従来、尿素を安定化させ得る外用組成物の処方について種々検討されている。例えば、特許文献１には、尿素を含む外用組成物において、グリシン等の中性アミノ酸を配合することによって尿素を安定化が図られることが開示されている。また、特許文献２には、外用組成物に尿素１０～２５重量％、及びレチノール又はその誘導体を含有させることにより、優れた製剤安定性を備えさせ得ることが開示されている。
Urea has a water retention effect by forming a hydrogen bond with water in the keratin and an effect of removing or softening unnecessary keratin due to protein denaturation, and is used in external compositions. On the other hand, since urea is easily hydrolyzed in the external composition, it is necessary to stabilize the urea in the external composition containing urea. Therefore, various studies have been made on the formulation of an external composition capable of stabilizing urea. For example, Patent Document 1 discloses that urea can be stabilized by blending a neutral amino acid such as glycine in an external composition containing urea. Further, Patent Document 2 discloses that the external composition can be provided with excellent pharmaceutical stability by containing 10 to 25% by weight of urea and retinol or a derivative thereof.
一方、サリチル酸、サリチル酸誘導体、及びこれらの塩等のサリチル酸系抗炎症剤は、消炎鎮痛用途で、外用組成物に使用されている。
On the other hand, salicylic acid, salicylic acid derivatives, and salicylic acid-based anti-inflammatory agents such as salts thereof are used in external compositions for anti-inflammatory and analgesic applications.
また、乳化製剤は、水性成分と油性成分を配合でき、様々な製剤処方に対応できると共に、皮膚に適用した際の使用感も優れているため、外用組成物の分野で汎用されている。
In addition, the emulsified preparation is widely used in the field of external composition because it can contain an aqueous component and an oily component, can be used for various preparation formulations, and has an excellent usability when applied to the skin.
近年、外用組成物の機能性の向上に対する消費者の要望が高まっており、このような消費者ニーズに追従するために、尿素及びサリチル酸系抗炎症剤を含む外用乳化組成物の開発が望まれている。
In recent years, consumer demand for improving the functionality of external compositions has increased, and in order to meet such consumer needs, it is desired to develop an external emulsified composition containing urea and a salicylic acid-based anti-inflammatory agent. ing.
本発明者は、本発明者は、尿素及びサリチル酸系抗炎症剤を含む外用乳化組成物を開発すべく種々検討を行ったところ、尿素及びサリチル酸系抗炎症剤を含む外用乳化組成物では、保存により相分離及び尿素の分解が生じ、保存安定性の点で問題があることを知得した。
The present inventor has conducted various studies to develop an external emulsified composition containing urea and a salicylic acid anti-inflammatory agent, and found that the external emulsified composition containing urea and a salicylic acid anti-inflammatory agent is preserved. It was found that there was a problem in terms of storage stability due to phase separation and decomposition of urea.
そこで、本発明は、尿素及びサリチル酸系抗炎症剤を含み、保存による相分離及び尿素の分解を抑制できる外用乳化組成物を提供することを課題とする。
Therefore, it is an object of the present invention to provide an external emulsified composition containing urea and a salicylic acid-based anti-inflammatory agent and capable of suppressing phase separation and urea decomposition during storage.
本発明者は、前記課題を解決すべく鋭意検討を行ったところ、尿素とサリチル酸系抗炎症剤に加えて、炭素数１４以上の飽和脂肪酸及び／又はその塩と親油性界面活性剤を含む外用乳化組成物は、保存による相分離及び尿素の分解を抑制でき、優れた保存安定性を備え得ることを見出した。本発明は、かかる知見に基づいて、更に検討を重ねることにより完成したものである。
As a result of diligent studies to solve the above problems, the present inventor has conducted an external application containing a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof and an oil-based surfactant in addition to urea and a salicylic acid-based anti-inflammatory agent. It has been found that the emulsified composition can suppress the phase separation and the decomposition of urea by storage and can have excellent storage stability. The present invention has been completed by further studies based on such findings.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項１． (A)尿素、(B)サリチル酸系抗炎症剤、(C)炭素数１４以上の飽和脂肪酸及び／又はその塩、並びに(D)親油性界面活性剤を含む、外用乳化組成物。
項２． 前記(D)成分が、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、及びポリオキシエチレン硬化ヒマシ油よりなる群から選択される少なくとも１種である、項１に記載の外用乳化組成物。
項３． グリシンを含まない、項１又は２に記載の外用乳化組成物。 That is, the present invention provides the inventions of the following aspects.
Item 1. An external emulsified composition comprising (A) urea, (B) a salicylic acid-based anti-inflammatory agent, (C) a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof, and (D) a lipophilic surfactant.
Item 2. Item 2. The external emulsification composition according to Item 1, wherein the component (D) is at least one selected from the group consisting of a sorbitan fatty acid ester, a glycerin fatty acid ester, and a polyoxyethylene hydrogenated castor oil.
Item 3. Item 2. The external emulsified composition according to Item 1 or 2, which does not contain glycine.
項１． (A)尿素、(B)サリチル酸系抗炎症剤、(C)炭素数１４以上の飽和脂肪酸及び／又はその塩、並びに(D)親油性界面活性剤を含む、外用乳化組成物。
項２． 前記(D)成分が、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、及びポリオキシエチレン硬化ヒマシ油よりなる群から選択される少なくとも１種である、項１に記載の外用乳化組成物。
項３． グリシンを含まない、項１又は２に記載の外用乳化組成物。 That is, the present invention provides the inventions of the following aspects.
Item 1. An external emulsified composition comprising (A) urea, (B) a salicylic acid-based anti-inflammatory agent, (C) a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof, and (D) a lipophilic surfactant.
Item 2. Item 2. The external emulsification composition according to Item 1, wherein the component (D) is at least one selected from the group consisting of a sorbitan fatty acid ester, a glycerin fatty acid ester, and a polyoxyethylene hydrogenated castor oil.
Item 3. Item 2. The external emulsified composition according to Item 1 or 2, which does not contain glycine.
本発明の外用乳化組成物によれば、尿素及びサリチル酸系抗炎症剤を含んでいながらも、保存による相分離及び尿素の分解を抑制でき、優れた保存安定性を備えることができる。
According to the external emulsification composition of the present invention, although it contains urea and a salicylic acid-based anti-inflammatory agent, phase separation and decomposition of urea due to storage can be suppressed, and excellent storage stability can be provided.
１．外用乳化組成物
本発明の外用乳化組成物は、(A)尿素、(B)サリチル酸系抗炎症剤、(C)炭素数１４以上の飽和脂肪酸及び／又はその塩、並びに(D)親油性界面活性剤を含むことを特徴とする。以下、本発明の外用乳化組成物について詳述する。 1. 1. External emulsification composition The external emulsified composition of the present invention comprises (A) urea, (B) a salicylic acid-based anti-inflammatory agent, (C) a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof, and (D) a lipophilic surfactant. It is characterized by containing an activator. Hereinafter, the external emulsified composition of the present invention will be described in detail.
本発明の外用乳化組成物は、(A)尿素、(B)サリチル酸系抗炎症剤、(C)炭素数１４以上の飽和脂肪酸及び／又はその塩、並びに(D)親油性界面活性剤を含むことを特徴とする。以下、本発明の外用乳化組成物について詳述する。 1. 1. External emulsification composition The external emulsified composition of the present invention comprises (A) urea, (B) a salicylic acid-based anti-inflammatory agent, (C) a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof, and (D) a lipophilic surfactant. It is characterized by containing an activator. Hereinafter, the external emulsified composition of the present invention will be described in detail.
［(A)尿素］
本発明の外用乳化組成物は、尿素（(A)成分と表記することもある）を含有する。尿素は、角質での水分保持作用や不要な角質の除去又は軟化作用等を有することが知られている公知の成分である。 [(A) Urea]
The external emulsified composition of the present invention contains urea (sometimes referred to as component (A)). Urea is a known component known to have a water retention action in the keratin, an unnecessary keratin removal or softening action, and the like.
本発明の外用乳化組成物は、尿素（(A)成分と表記することもある）を含有する。尿素は、角質での水分保持作用や不要な角質の除去又は軟化作用等を有することが知られている公知の成分である。 [(A) Urea]
The external emulsified composition of the present invention contains urea (sometimes referred to as component (A)). Urea is a known component known to have a water retention action in the keratin, an unnecessary keratin removal or softening action, and the like.
本発明の外用乳化組成物における(A)成分の含有量としては、付与すべき薬効、外用乳化組成物の用途等に応じて適宜設定すればよいが、例えば、１～３０重量％、好ましくは５～２５重量％、より好ましくは１０～２０重量％が挙げられる。
The content of the component (A) in the external emulsified composition of the present invention may be appropriately set according to the medicinal effect to be imparted, the intended use of the external emulsified composition, etc., and is, for example, 1 to 30% by weight, preferably 1 to 30% by weight. 5 to 25% by weight, more preferably 10 to 20% by weight.
［(B)サリチル酸系抗炎症剤］
本発明の外用乳化組成物は、サリチル酸系抗炎症剤（(B)成分と表記することもある）を含有する。 [(B) Salicylic acid anti-inflammatory agent]
The external emulsified composition of the present invention contains a salicylic acid-based anti-inflammatory agent (sometimes referred to as a component (B)).
本発明の外用乳化組成物は、サリチル酸系抗炎症剤（(B)成分と表記することもある）を含有する。 [(B) Salicylic acid anti-inflammatory agent]
The external emulsified composition of the present invention contains a salicylic acid-based anti-inflammatory agent (sometimes referred to as a component (B)).
サリチル酸系抗炎症剤としては、具体的には、サリチル酸、サリチル酸の誘導体、及びこれらの塩が挙げられる。サリチル酸の誘導体としては、例えば、アセチルサリチル酸（アスピリン）、サリチルアミド（エテンザミド）、スルホサリチル酸、サリチル酸メチル、サリチル酸エチル、サリチル酸グリコール、サリチル酸エチレングリコール、サリチル酸ジプロピレングリコール、サリチル酸チタン、サリチル酸２－エチルヘキシル、サリチル酸ホモメンチル、サリチル酸フェニル等が挙げられる。サリチル酸及びその誘導体の塩としては、例えば、ナトリウム、カリウム等のアルカリ金属塩；マグネシウム等のアルカリ土類金属塩が挙げられる。
Specific examples of the salicylic acid-based anti-inflammatory agent include salicylic acid, salicylic acid derivatives, and salts thereof. Examples of the derivative of salicylic acid include acetylsalicylic acid (aspirin), salicylic acid (ethenzamid), sulfosalicylic acid, methyl salicylic acid, ethyl salicylic acid, glycol salicylate, ethylene glycol salicylate, dipropylene glycol salicylate, titanium salicylate, 2-ethylhexyl salicylate, and salicylic acid. Examples thereof include homomentyl and phenyl salicylate. Examples of salts of salicylic acid and its derivatives include alkali metal salts such as sodium and potassium; and alkaline earth metal salts such as magnesium.
これらのサリチル酸系抗炎症剤は、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
These salicylic acid-based anti-inflammatory agents may be used alone or in combination of two or more.
これらのサリチル酸系抗炎症剤の中でも、好ましくはサリチル酸、サリチル酸の塩、サリチル酸エチル、サリチル酸メチル、より好ましくはサリチル酸が挙げられる。
Among these salicylic acid-based anti-inflammatory agents, salicylic acid, salts of salicylic acid, ethyl salicylate, methyl salicylate, and more preferably salicylic acid can be mentioned.
本発明の外用乳化組成物における(B)成分の含有量としては、付与すべき薬効、外用乳化組成物の用途等に応じて適宜設定すればよいが、例えば、(B)成分の総量で０．０１～１重量％、好ましくは０．０５～０．５重量％、より好ましくは０．１～０．５重量％が挙げられる。
The content of the component (B) in the external emulsified composition of the present invention may be appropriately set according to the medicinal effect to be imparted, the intended use of the external emulsified composition, etc., but for example, the total amount of the component (B) is 0. 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight, and more preferably 0.1 to 0.5% by weight.
本発明の外用乳化組成物において、(A)成分と(B)成分の比率については、特に制限されないが、例えば、(A)成分の総量１００重量部当たり、(B)成分が総量で０．０１～３００重量部、好ましくは０．０５～１００重量部、より好ましくは０．１～５０重量部が挙げられる。
In the external emulsified composition of the present invention, the ratio of the component (A) to the component (B) is not particularly limited, but for example, the total amount of the component (B) is 0. Examples thereof include 01 to 300 parts by weight, preferably 0.05 to 100 parts by weight, and more preferably 0.1 to 50 parts by weight.
［(C)炭素数１４以上の飽和脂肪酸及び／又はその塩］
本発明の外用乳化組成物は、炭素数１４以上の飽和脂肪酸及び／又はその塩（(C)成分と表記することもある）を含有する。 [(C) Saturated fatty acids having 14 or more carbon atoms and / or salts thereof]
The external emulsified composition of the present invention contains a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof (sometimes referred to as a component (C)).
本発明の外用乳化組成物は、炭素数１４以上の飽和脂肪酸及び／又はその塩（(C)成分と表記することもある）を含有する。 [(C) Saturated fatty acids having 14 or more carbon atoms and / or salts thereof]
The external emulsified composition of the present invention contains a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof (sometimes referred to as a component (C)).
飽和脂肪酸及び／又はその塩は、炭素数が１４以上であればよいが、保存による相分離及び尿素の分解をより一層効果的に抑制するという観点から、好ましくは炭素数１４～３０、より好ましくは炭素数１４～２４、更に好ましくは炭素数１４～２２、特に好ましくは炭素数１８が挙げられる。飽和脂肪酸として、より具体的には、ミリスチリン酸、パルミチン酸、ステアリン酸、アラキジン酸、ベヘン酸、リグノセリン酸、セロチン酸、モンタン酸、メリシン酸；好ましくはミリスチリン酸、パルミチン酸、ステアリン酸、アラキジン酸、ベヘン酸、リグノセリン酸：より好ましくはミリスチリン酸、パルミチン酸、ステアリン酸、アラキジン酸、ベヘン酸；更に好ましくはステアリン酸が挙げられる。
The saturated fatty acid and / or a salt thereof may have 14 or more carbon atoms, but is preferably 14 to 30 carbon atoms, more preferably, from the viewpoint of more effectively suppressing phase separation and urea decomposition during storage. 14 to 24 carbon atoms, more preferably 14 to 22 carbon atoms, and particularly preferably 18 carbon atoms. Saturated fatty acids, more specifically, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoseric acid, cellotic acid, montanic acid, melicic acid; preferably myristic acid, palmitic acid, stearic acid, arachidic acid. , Bechenic acid, lignoseric acid: more preferably myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid; more preferably stealic acid.
炭素数１４以上の飽和脂肪酸の塩としては、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩が挙げられる。
Examples of the salt of saturated fatty acid having 14 or more carbon atoms include alkali metal salts such as sodium salt and potassium salt.
本発明の外用組成物は、(C)成分として、炭素数１４以上の飽和脂肪酸及びその塩の中から、１種を選択して使用してもよく、２種以上を組み合わせて使用してもよい。
In the external composition of the present invention, as the component (C), one may be selected and used from among saturated fatty acids having 14 or more carbon atoms and salts thereof, or two or more thereof may be used in combination. good.
本発明の外用乳化組成物における(C)成分の含有量としては、特に制限されないが、例えば、(C)成分の総量で０．０１～１０重量％、好ましくは０．１～６重量％、より好ましくは１～６重量％が挙げられる。
The content of the component (C) in the external emulsified composition of the present invention is not particularly limited, but for example, the total amount of the component (C) is 0.01 to 10% by weight, preferably 0.1 to 6% by weight. More preferably, 1 to 6% by weight is mentioned.
本発明の外用乳化組成物において、(A)成分と(C)成分の比率については、特に制限されないが、例えば、(A)成分の総量１００重量部当たり、(C)成分が総量で０．１～１２００重量部、好ましくは０．１～１００重量部、より好ましくは０．１～５０重量部が挙げられる。
In the external emulsified composition of the present invention, the ratio of the component (A) to the component (C) is not particularly limited, but for example, the total amount of the component (C) is 0. Examples thereof include 1 to 1200 parts by weight, preferably 0.1 to 100 parts by weight, and more preferably 0.1 to 50 parts by weight.
［(D)親油性界面活性剤］
本発明の外用乳化組成物は、親油性界面活性剤（(D)成分と表記することもある）を含有する。 [(D) Lipophilic surfactant]
The external emulsified composition of the present invention contains a lipophilic surfactant (sometimes referred to as component (D)).
本発明の外用乳化組成物は、親油性界面活性剤（(D)成分と表記することもある）を含有する。 [(D) Lipophilic surfactant]
The external emulsified composition of the present invention contains a lipophilic surfactant (sometimes referred to as component (D)).
本発明において、親油性界面活性剤とは、水に対する親和性よりも油剤に対する親和性が高い性質を有する界面活性剤である。親油性界面活性剤として、具体的には、ＨＬＢ値が８以下、好ましくはＨＬＢ値が１～８、より好ましくはＨＬＢ値が２～６．５であるノニオン性界面活性剤が挙げられる。なお、本発明において、界面活性剤のＨＬＢ値は、川上法（HLB値=7+11.7log(親水部の式量の総和/親油部式量の総和)）に従って算出される値である。
In the present invention, the lipophilic surfactant is a surfactant having a property of having a higher affinity for an oil agent than an affinity for water. Specific examples of the lipophilic surfactant include nonionic surfactants having an HLB value of 8 or less, preferably an HLB value of 1 to 8, and more preferably an HLB value of 2 to 6.5. In the present invention, the HLB value of the surfactant is a value calculated according to the upstream method (HLB value = 7 + 11.7 log (total of the formula amounts of the hydrophilic part / the total of the formula amount of the base oil part)).
親油性界面活性剤としては、例えば、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油、ポリグリセリン脂肪酸エステル、プロピレングリコール脂肪酸エステル等のノニオン性界面活性剤の内、前記ＨＬＢ値を満たすものが挙げられる。
Examples of the oil-based surfactant include nonionic surfactants such as sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, and propylene glycol fatty acid ester, which satisfy the HLB value. Can be mentioned.
これらの親油性界面活性剤中でも、保存による相分離及び尿素の分解をより一層効果的に抑制するという観点から、好ましくはソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油、より好ましくはソルビタン脂肪酸エステル、グリセリン脂肪酸エステルが挙げられる。
Among these lipophilic surfactants, sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, and more preferably sorbitan are preferable from the viewpoint of more effectively suppressing phase separation and urea decomposition during storage. Examples thereof include fatty acid ester and glycerin fatty acid ester.
前記ソルビタン脂肪酸エステルを構成する脂肪酸の炭素数としては、例えば、１０～２２個、好ましくは１４～２２個、より好ましくは１６～２０個が挙げられる。前記ソルビタン脂肪酸エステル１分子当たりに結合している脂肪酸の数としては、例えば、１～４個、好ましくは１～３個が挙げられる。ソルビタン脂肪酸エステルとして、具体的には、モノオレイン酸ソルビタン、モノステアリン酸ソルビタン、セスキオレイン酸ソルビタン、ヤシ油脂肪酸ソルビタン、モノパルミチン酸ソルビタン、トリステアリン酸ソルビタン、トリオレイン酸ソルビタン等が挙げられる。これらのソルビタン脂肪酸エステルの中でも、好ましくはモノステアリン酸ソルビタン、セスキステアリン酸ソルビタン、トリステアリン酸ソルビタン、より好ましくはモノステアリン酸ソルビタンが挙げられる。
Examples of the carbon number of the fatty acid constituting the sorbitan fatty acid ester include 10 to 22, preferably 14 to 22, and more preferably 16 to 20. Examples of the number of fatty acids bound per molecule of the sorbitan fatty acid ester include 1 to 4, preferably 1 to 3. Specific examples of the sorbitan fatty acid ester include sorbitan monooleate, sorbitan monostearate, sorbitan sesquioleate, sorbitan coconut oil fatty acid, sorbitan monopalmitate, sorbitan tristearate, and sorbitan trioleate. Among these sorbitan fatty acid esters, sorbitan monostearate, sorbitan sesquistearate, sorbitan tristearate, and more preferably sorbitan monostearate are mentioned.
前記グリセリン脂肪酸エステルを構成する脂肪酸の炭素数としては、例えば、１０～２２個、好ましくは１４～２２個、より好ましくは１６～２０個が挙げられる。前記グリセリン脂肪酸１分子当たりに結合している脂肪酸の数としては、特に制限されないが、例えば、１～３個、好ましくは１又は２個、より好ましくは１個が挙げられる。前記グリセリン脂肪酸エステルとして、具体的には、モノミリスチン酸グリセリル、モノステアリン酸グリセリル、モノイソステアリン酸グリセリル、モノオレイン酸グリセリル、ジミリスチン酸グリセリル、ジステアリン酸グリセリル、ジイソステアリン酸グリセリル、ジオレイン酸グリセリル等が挙げられる。これらのグリセリン脂肪酸エステルの中でも、好ましくは、モノステアリン酸グリセリル、モノミリスチン酸グリセリルが挙げられる。
Examples of the carbon number of the fatty acid constituting the glycerin fatty acid ester include 10 to 22, preferably 14 to 22, and more preferably 16 to 20. The number of fatty acids bound to one molecule of the glycerin fatty acid is not particularly limited, and examples thereof include 1 to 3, preferably 1 or 2, and more preferably 1. Specific examples of the glycerin fatty acid ester include glyceryl monomyristate, glyceryl monostearate, glyceryl monoisostearate, glyceryl monooleate, glyceryl dimyristate, glyceryl distearate, glyceryl diisostearate, and glyceryl dioleate. Be done. Among these glycerin fatty acid esters, glyceryl monostearate and glyceryl monomyristate are preferable.
前記ポリオキシエチレン硬化ヒマシ油における酸化エチレン（ＥＯ）の平均付加モル数としては、例えば、３～１００モル、好ましくは３～５０モル、より好ましくは３～２０モルが挙げられる。前記ポリオキシエチレン硬化ヒマシ油としては、具体的には、ポリオキシエチレン硬化ヒマシ油５、ポリオキシエチレン硬化ヒマシ油１０等が挙げられる。これらのポリオキシエチレン硬化ヒマシ油の中でも、好ましくは、ポリオキシエチレン硬化ヒマシ油１０が挙げられる。
Examples of the average number of moles of ethylene oxide (EO) added to the polyoxyethylene hydrogenated castor oil include 3 to 100 mol, preferably 3 to 50 mol, and more preferably 3 to 20 mol. Specific examples of the polyoxyethylene cured castor oil include polyoxyethylene cured castor oil 5, polyoxyethylene cured castor oil 10, and the like. Among these polyoxyethylene cured castor oils, preferably, polyoxyethylene cured castor oil 10 is mentioned.
これらの)親油性界面活性剤は、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
These) lipophilic surfactants may be used alone or in combination of two or more.
本発明の外用乳化組成物における(D)成分の含有量としては、特に制限されないが、例えば、(D)成分の総量で０．０１～２０重量％、好ましくは０．０５～１０重量％、より好ましくは０．２～５重量％が挙げられる。
The content of the component (D) in the external emulsified composition of the present invention is not particularly limited, but for example, the total amount of the component (D) is 0.01 to 20% by weight, preferably 0.05 to 10% by weight. More preferably, 0.2 to 5% by weight is mentioned.
本発明の外用乳化組成物において、(A)成分と(D)成分の比率については、特に制限されないが、例えば、(A)成分の総量１００重量部当たり、(D)成分が総量で０．０１～５００重量部、好ましくは０．０５～２００重量部、より好ましくは０．１～５０重量部が挙げられる。
In the external emulsified composition of the present invention, the ratio of the component (A) to the component (D) is not particularly limited, but for example, the total amount of the component (D) is 0. Examples thereof include 01 to 500 parts by weight, preferably 0.05 to 200 parts by weight, and more preferably 0.1 to 50 parts by weight.
［グリシン・中性アミノ酸］
本発明の外用乳化組成物は、グリシンを含んでいてもよいが、グリシンを含まないことが好ましい。従来、グリシンは尿素を安定化させる作用があることが知られているが、本発明の外用乳化組成物では、グリシンを含まない場合には、保存による尿素の分解をより一層効果的に抑制することが可能になる。 [Glycine / Neutral Amino Acid]
The external emulsified composition of the present invention may contain glycine, but preferably does not contain glycine. Conventionally, it is known that glycine has an action of stabilizing urea, but in the case of the external emulsified composition of the present invention, when glycine is not contained, the decomposition of urea by storage is more effectively suppressed. Will be possible.
本発明の外用乳化組成物は、グリシンを含んでいてもよいが、グリシンを含まないことが好ましい。従来、グリシンは尿素を安定化させる作用があることが知られているが、本発明の外用乳化組成物では、グリシンを含まない場合には、保存による尿素の分解をより一層効果的に抑制することが可能になる。 [Glycine / Neutral Amino Acid]
The external emulsified composition of the present invention may contain glycine, but preferably does not contain glycine. Conventionally, it is known that glycine has an action of stabilizing urea, but in the case of the external emulsified composition of the present invention, when glycine is not contained, the decomposition of urea by storage is more effectively suppressed. Will be possible.
また、本発明の外用乳化組成物の一態様として、中性アミノ酸（側鎖にアミノ基又はカルボキシル基が含まれていないアミノ酸）を含まないことが挙げられる。
Further, as one aspect of the external emulsified composition of the present invention, it is mentioned that it does not contain a neutral amino acid (an amino acid whose side chain does not contain an amino group or a carboxyl group).
［親水性界面活性剤］
本発明の外用乳化組成物は、必要に応じて、親水性界面活性剤を含んでいてもよい。本発明において、親水性界面活性剤とは、油剤に対する親和性よりも水に対する親和性が高い性質を有する界面活性剤である。親水性界面活性剤として、具体的には、ＨＬＢ値が８超のノニオン性界面活性剤が挙げられる。 [Hydrophilic surfactant]
The external emulsified composition of the present invention may contain a hydrophilic surfactant, if necessary. In the present invention, the hydrophilic surfactant is a surfactant having a property of having a higher affinity for water than an affinity for an oil agent. Specific examples of the hydrophilic surfactant include nonionic surfactants having an HLB value of more than 8.
本発明の外用乳化組成物は、必要に応じて、親水性界面活性剤を含んでいてもよい。本発明において、親水性界面活性剤とは、油剤に対する親和性よりも水に対する親和性が高い性質を有する界面活性剤である。親水性界面活性剤として、具体的には、ＨＬＢ値が８超のノニオン性界面活性剤が挙げられる。 [Hydrophilic surfactant]
The external emulsified composition of the present invention may contain a hydrophilic surfactant, if necessary. In the present invention, the hydrophilic surfactant is a surfactant having a property of having a higher affinity for water than an affinity for an oil agent. Specific examples of the hydrophilic surfactant include nonionic surfactants having an HLB value of more than 8.
親水性界面活性剤としては、例えば、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレンアルキルエーテル、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ポリオキシエチレングリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレンソルビット脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油、ポリエチレングリコール脂肪酸エステル、レシチン誘導体等のノニオン性界面活性剤の内、前記ＨＬＢ値を満たすものが挙げられる。これらの親水性界面活性剤中でも、保存による相分離及び尿素の分解をより一層効果的に抑制するという観点から、好ましくはポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレンアルキルエーテルが挙げられる。
Examples of the hydrophilic surfactant include polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkyl ether, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, sorbitan fatty acid ester, and polyoxyethylene sorbit fatty acid ester. Among nonionic surfactants such as polyoxyethylene hydrogenated castor oil, polyethylene glycol fatty acid ester, and lecithin derivative, those satisfying the above HLB value can be mentioned. Among these hydrophilic surfactants, polyoxyethylene sorbitan fatty acid ester and polyoxyethylene alkyl ether are preferably mentioned from the viewpoint of more effectively suppressing phase separation and urea decomposition during storage.
前記ポリオキシエチレンソルビタン脂肪酸エステルを構成する酸化エチレン（ＥＯ）の平均付加モル数としては、例えば、５～５０モル、好ましくは１０～３０モル、より好ましくは１５～２５モルが挙げられる。ポリオキシエチレンソルビタン脂肪酸エステルを構成する脂肪酸の炭素数としては、例えば、１０～２２個、好ましくは１４～２２個、より好ましくは１６～２０個が挙げられる。ポリオキシエチレンソルビタン脂肪酸エステルとして、具体的には、モノオレイン酸ポリオキシエチレンソルビタン、トリオレイン酸ポリオキシエチレンソルビタン、トリステアリン酸ポリオキシエチレンソルビタン、モノステアリン酸ポリオキシエチレンソルビタン、モノパルミチン酸ポリオキシエチレンソルビタン、モノラウリン酸ポリオキシエチレンソルビタン等が挙げられる。これらのポリオキシエチレンソルビタン脂肪酸エステルの中でも、好ましくは、酸化エチレン（ＥＯ）の平均付加モル数が２０であるモノステアリン酸ポリオキシエチレンソルビタン（ポリソルベート６０）が挙げられる。
Examples of the average number of moles of ethylene oxide (EO) constituting the polyoxyethylene sorbitan fatty acid ester include 5 to 50 mol, preferably 10 to 30 mol, and more preferably 15 to 25 mol. Examples of the carbon number of the fatty acid constituting the polyoxyethylene sorbitan fatty acid ester include 10 to 22, preferably 14 to 22, and more preferably 16 to 20. Specific examples of the polyoxyethylene sorbitan fatty acid ester include monooleic acid polyoxyethylene sorbitan, trioleic acid polyoxyethylene sorbitan, tristearate polyoxyethylene sorbitan, monostearate polyoxyethylene sorbitan, and monopalmitic acid polyoxy. Examples thereof include ethylene sorbitan and polyoxyethylene sorbitan monolaurate. Among these polyoxyethylene sorbitan fatty acid esters, preferably, monostearate polyoxyethylene sorbitan (polysorbate 60) having an average addition mole number of ethylene oxide (EO) of 20 can be mentioned.
前記ポリオキシエチレンアルキルエーテルを構成する酸化エチレン（ＥＯ）の平均付加モル数としては、例えば、２～５０モル、好ましくは５～３０モル、より好ましくは１５～２５モルが挙げられる。ポリオキシエチレンアルキルエーテルを構成するアルキル基の炭素数としては、特に制限されないが、例えば、１０～２４個、好ましくは１４～２４個、より好ましくは１６～２４個が挙げられる。ポリオキシエチレンアルキルエーテルとして、具体的には、ポリオキシエチレンセチルエーテル、ポリオキシエチレンオレイルエーテル、ポリオキシエチレンステアリルエーテル、ポリオキシエチレンベヘニルエーテル、ポリオキシエチレンアラキルエーテル等が挙げられる。これらのポリオキシエチレンアルキルエーテルの中でも、保存による変色をより一層効果的に抑制するという観点から、好ましくはポリオキシエチレンアラキルエーテルが挙げられる。
Examples of the average number of moles of ethylene oxide (EO) constituting the polyoxyethylene alkyl ether include 2 to 50 mol, preferably 5 to 30 mol, and more preferably 15 to 25 mol. The number of carbon atoms of the alkyl group constituting the polyoxyethylene alkyl ether is not particularly limited, and examples thereof include 10 to 24 carbon atoms, preferably 14 to 24 carbon atoms, and more preferably 16 to 24 carbon atoms. Specific examples of the polyoxyethylene alkyl ether include polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, and polyoxyethylene araquil ether. Among these polyoxyethylene alkyl ethers, polyoxyethylene alkyl ethers are preferable from the viewpoint of more effectively suppressing discoloration due to storage.
本発明の外用乳化組成物における親水性界面活性剤を含有させる場合、その含有量としては、特に制限されないが、例えば、親水性界面活性剤の総量で０．５～２０重量％、好ましくは１～１５重量％、より好ましくは１．５～５重量％が挙げられる。
When the hydrophilic surfactant in the external emulsification composition of the present invention is contained, the content thereof is not particularly limited, but for example, the total amount of the hydrophilic surfactant is 0.5 to 20% by weight, preferably 1. -15% by weight, more preferably 1.5-5% by weight.
［多価アルコール］
本発明の外用乳化組成物には、必要に応じて、多価アルコールが含まれていてもよい。 [Multivalent alcohol]
The external emulsified composition of the present invention may contain a polyhydric alcohol, if necessary.
本発明の外用乳化組成物には、必要に応じて、多価アルコールが含まれていてもよい。 [Multivalent alcohol]
The external emulsified composition of the present invention may contain a polyhydric alcohol, if necessary.
多価アルコールとしては、薬学的に許容されることを限度として、特に制限されないが、例えば、１，３－ブチレングリコール、プロピレングリコール、ジプロピレングリコール、ポリプロピレングリコール、グリセリン等が挙げられる。これらの多価アルコールの中でも、好ましくはグリセリンが挙げられる。これらの多価アルコールは、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。
The polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include 1,3-butylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, and glycerin. Among these polyhydric alcohols, glycerin is preferable. These polyhydric alcohols may be used alone or in combination of two or more.
本発明の外用乳化組成物に、多価アルコールを含有させる場合、その含有量については、特に制限されないが、例えば、多価アルコールの総量０．１～３０重量％、好ましくは０．５～２０重量％、より好ましくは１～１０重量％が挙げられる。
When the external emulsified composition of the present invention contains a polyhydric alcohol, the content thereof is not particularly limited, but for example, the total amount of the polyhydric alcohol is 0.1 to 30% by weight, preferably 0.5 to 20%. By weight%, more preferably 1 to 10% by weight.
［(C)成分以外の油性基剤］
本発明の外用乳化組成物は、所望の製剤形態への調製等のために、必要に応じて、前記(C)成分以外の油性基剤が更に含まれていてもよい。(C)成分以外の油性基剤としては、薬学的に許容されることを限度として特に制限されないが、例えば、高級アルコール、炭化水素油、脂肪酸アルキルエステル、植物油、動物油、シリコーンオイル等が挙げられる。これらの油性基剤（(C)成分以外）は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。これらの油性基剤（(C)成分以外）の中でも、好ましくは高級アルコール、炭化水素油が挙げられる。 [Oil-based bases other than (C) component]
The external emulsified composition of the present invention may further contain an oily base other than the component (C), if necessary, for preparation into a desired pharmaceutical form. The oily base other than the component (C) is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include higher alcohols, hydrocarbon oils, fatty acid alkyl esters, vegetable oils, animal oils, and silicone oils. .. These oily bases (other than the component (C)) may be used alone or in combination of two or more. Among these oil-based bases (other than the component (C)), higher alcohols and hydrocarbon oils are preferable.
本発明の外用乳化組成物は、所望の製剤形態への調製等のために、必要に応じて、前記(C)成分以外の油性基剤が更に含まれていてもよい。(C)成分以外の油性基剤としては、薬学的に許容されることを限度として特に制限されないが、例えば、高級アルコール、炭化水素油、脂肪酸アルキルエステル、植物油、動物油、シリコーンオイル等が挙げられる。これらの油性基剤（(C)成分以外）は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。これらの油性基剤（(C)成分以外）の中でも、好ましくは高級アルコール、炭化水素油が挙げられる。 [Oil-based bases other than (C) component]
The external emulsified composition of the present invention may further contain an oily base other than the component (C), if necessary, for preparation into a desired pharmaceutical form. The oily base other than the component (C) is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include higher alcohols, hydrocarbon oils, fatty acid alkyl esters, vegetable oils, animal oils, and silicone oils. .. These oily bases (other than the component (C)) may be used alone or in combination of two or more. Among these oil-based bases (other than the component (C)), higher alcohols and hydrocarbon oils are preferable.
高級アルコールとしては、薬学的に許容されるものである限り特に制限されないが、例えば、炭素数１２～３４の１価アルコールが挙げられ、具体的には、ラウリルアルコール、セタノール、ステアリルアルコール、セトステアリルアルコール、オレイルアルコール、アラキジルアルコール、ベヘニルアルコール、ミリシルアルコール、ゲジルアルコール等が挙げられる。これらの高級アルコールの中でも、好ましくはステアリルアルコール、セトステアリルアルコールが挙げられる。
The higher alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include monohydric alcohols having 12 to 34 carbon atoms, and specific examples thereof include lauryl alcohol, cetanol, stearyl alcohol, and cetostearyl. Examples thereof include alcohol, oleyl alcohol, arachidyl alcohol, behenyl alcohol, myricyl alcohol, and gesil alcohol. Among these higher alcohols, stearyl alcohol and cetostearyl alcohol are preferable.
炭化水素油としては、薬学的に許容されるものである限り特に制限されないが、例えば、流動パラフィン、α－オレフィンオリゴマー、ワセリン、マイクロクリスタリンワックス、ゲル化炭化水素（プラスチベース等）、水添ポリイソブテン等が挙げられる。これらの炭化水素油の中でも、好ましくは流動パラフィン、ワセリンが挙げられる。
The hydrocarbon oil is not particularly limited as long as it is pharmaceutically acceptable, but for example, liquid paraffin, α-olefin oligomer, petrolatum, microcrystalline wax, gelled hydrocarbon (plastibase, etc.), hydrogenated polyisobutene, etc. Can be mentioned. Among these hydrocarbon oils, liquid paraffin and petrolatum are preferable.
本発明の外用乳化組成物に油性基剤（(C)成分以外）を含有させる場合、その含有量については、製剤形態、使用感等に応じて適宜設定すればよいが、例えば、油性基剤（(C)成分以外）の総量で５～８０重量％、好ましくは１０～６０重量％、より好ましくは１０～３０重量％が挙げられる。
When the external emulsified composition of the present invention contains an oil-based base (other than the component (C)), the content thereof may be appropriately set according to the pharmaceutical form, usability, etc., but for example, the oil-based base. The total amount of (other than the component (C)) is 5 to 80% by weight, preferably 10 to 60% by weight, and more preferably 10 to 30% by weight.
［その他の成分］
本発明の外用乳化組成物は、前述する成分の他に、必要に応じて、通常使用される他の添加剤が含まれていてもよい。このような添加剤としては、例えば、１価低級アルコール、水性基剤、ｐＨ調節剤、緩衝剤、可溶化剤、防腐剤、保存剤、酸化防止剤、安定化剤、香料、着色料、水等が挙げられる。本発明の外用乳化組成物において、これらの添加剤を含有させる場合、その含有量については、使用する添加剤の種類等に応じて適宜設定すればよい。 [Other ingredients]
In addition to the above-mentioned components, the external emulsified composition of the present invention may contain other commonly used additives, if necessary. Examples of such additives include monohydric lower alcohols, aqueous bases, pH regulators, buffers, solubilizers, preservatives, preservatives, antioxidants, stabilizers, fragrances, colorants, and water. And so on. When these additives are contained in the external emulsification composition of the present invention, the content thereof may be appropriately set according to the type of the additive to be used and the like.
本発明の外用乳化組成物は、前述する成分の他に、必要に応じて、通常使用される他の添加剤が含まれていてもよい。このような添加剤としては、例えば、１価低級アルコール、水性基剤、ｐＨ調節剤、緩衝剤、可溶化剤、防腐剤、保存剤、酸化防止剤、安定化剤、香料、着色料、水等が挙げられる。本発明の外用乳化組成物において、これらの添加剤を含有させる場合、その含有量については、使用する添加剤の種類等に応じて適宜設定すればよい。 [Other ingredients]
In addition to the above-mentioned components, the external emulsified composition of the present invention may contain other commonly used additives, if necessary. Examples of such additives include monohydric lower alcohols, aqueous bases, pH regulators, buffers, solubilizers, preservatives, preservatives, antioxidants, stabilizers, fragrances, colorants, and water. And so on. When these additives are contained in the external emulsification composition of the present invention, the content thereof may be appropriately set according to the type of the additive to be used and the like.
本発明の外用乳化組成物は、前述する成分の他に、薬理成分が含まれていてもよい。このような薬理成分としては、例えば、ステロイド剤、抗ヒスタミン剤、局所麻酔剤、抗炎症剤（(B)成分以外）、保湿剤（(A)成分以外）、殺菌剤、抗菌剤、鎮痒剤、皮膚保護剤、血行促進成分、ビタミン類、ムコ多糖類等が挙げられる。これらの薬理成分は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、本発明の外用組成物において、これらの薬理成分を含有させる場合、その濃度については、使用する薬理成分の種類、期待する効果等に応じて適宜設定すればよい。
The external emulsified composition of the present invention may contain a pharmacological component in addition to the above-mentioned components. Examples of such pharmacological components include steroids, antihistamines, local anesthetics, anti-inflammatory agents (other than component (B)), moisturizers (other than component (A)), bactericides, antibacterial agents, antipruritic agents, and skin. Protective agents, blood circulation promoting ingredients, vitamins, mucopolysaccharides and the like can be mentioned. These pharmacological components may be used alone or in combination of two or more. When these pharmacological components are contained in the external composition of the present invention, the concentration thereof may be appropriately set according to the type of the pharmacological component used, the expected effect, and the like.
［乳化タイプ・製剤形態］
本発明の外用乳化組成物の乳化タイプは、水中油型又は油中水型のいずれであってもよいが、好ましくは水中油型が挙げられる。 [Emulsification type / pharmaceutical form]
The emulsification type of the external emulsification composition of the present invention may be either an oil-in-water type or a water-in-oil type, and an oil-in-water type is preferable.
本発明の外用乳化組成物の乳化タイプは、水中油型又は油中水型のいずれであってもよいが、好ましくは水中油型が挙げられる。 [Emulsification type / pharmaceutical form]
The emulsification type of the external emulsification composition of the present invention may be either an oil-in-water type or a water-in-oil type, and an oil-in-water type is preferable.
本発明の外用乳化組成物の製剤形態については、特に制限されないが、例えば、クリーム剤、乳液剤、ローション剤、リニメント剤、エアゾール剤等の外用医薬品が挙げられる。これらの中でも、好ましくはクリーム剤が挙げられる。
The formulation form of the external emulsified composition of the present invention is not particularly limited, and examples thereof include external pharmaceuticals such as creams, emulsions, lotions, liniments, and aerosols. Among these, a cream agent is preferably mentioned.
［用途］
本発明の外用乳化組成物の用途については、特に制限されないが、本発明の外用乳化組成物は、(A)成分に基づく角質の軟化又は除去作用及び保湿作用、(B)成分に基づく抗炎症作用を発揮できるので、角質の軟化又は除去、保湿、抗炎症等の用途に好適に使用される。特に、本発明の外用乳化組成物は、爪周りの角質を軟化させる効果に優れているので、爪周りの角質の軟化用途に好適に使用される。 [Use]
The use of the external emulsified composition of the present invention is not particularly limited, but the external emulsified composition of the present invention has a keratin softening or removing action and a moisturizing action based on the component (A), and an anti-inflammatory action based on the component (B). Since it can exert its action, it is suitably used for applications such as softening or removing keratin, moisturizing, and anti-inflammatory. In particular, the external emulsified composition of the present invention is excellent in the effect of softening the keratin around the nail, and is therefore suitably used for softening the keratin around the nail.
本発明の外用乳化組成物の用途については、特に制限されないが、本発明の外用乳化組成物は、(A)成分に基づく角質の軟化又は除去作用及び保湿作用、(B)成分に基づく抗炎症作用を発揮できるので、角質の軟化又は除去、保湿、抗炎症等の用途に好適に使用される。特に、本発明の外用乳化組成物は、爪周りの角質を軟化させる効果に優れているので、爪周りの角質の軟化用途に好適に使用される。 [Use]
The use of the external emulsified composition of the present invention is not particularly limited, but the external emulsified composition of the present invention has a keratin softening or removing action and a moisturizing action based on the component (A), and an anti-inflammatory action based on the component (B). Since it can exert its action, it is suitably used for applications such as softening or removing keratin, moisturizing, and anti-inflammatory. In particular, the external emulsified composition of the present invention is excellent in the effect of softening the keratin around the nail, and is therefore suitably used for softening the keratin around the nail.
［製造方法］
本発明の外用乳化組成物は、乳化タイプに応じて、公知の乳化製剤の製剤化手法に従って製造することができる。例えば、本発明の外用乳化組成物の製造方法としては、含有させる成分を水溶性成分と油性成分に分けて、水溶性成分を含む水相と、油性成分を含む油相とを調製し、これらを公知の手法に従って乳化させる方法が挙げられる。 [Production method]
The external emulsified composition of the present invention can be produced according to a known method for formulating an emulsified preparation, depending on the emulsified type. For example, in the method for producing an external emulsified composition of the present invention, the components to be contained are divided into a water-soluble component and an oil-based component, and an aqueous phase containing the water-soluble component and an oil phase containing the oil-based component are prepared. There is a method of emulsifying according to a known method.
本発明の外用乳化組成物は、乳化タイプに応じて、公知の乳化製剤の製剤化手法に従って製造することができる。例えば、本発明の外用乳化組成物の製造方法としては、含有させる成分を水溶性成分と油性成分に分けて、水溶性成分を含む水相と、油性成分を含む油相とを調製し、これらを公知の手法に従って乳化させる方法が挙げられる。 [Production method]
The external emulsified composition of the present invention can be produced according to a known method for formulating an emulsified preparation, depending on the emulsified type. For example, in the method for producing an external emulsified composition of the present invention, the components to be contained are divided into a water-soluble component and an oil-based component, and an aqueous phase containing the water-soluble component and an oil phase containing the oil-based component are prepared. There is a method of emulsifying according to a known method.
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。
The present invention will be described in more detail with reference to examples below, but the present invention is not limited thereto.
試験例１
表１及び２に示す組成の外用乳化組成物（クリーム状の水中油型乳化製剤）を調製した。具体的には、先ず、界面活性剤（モノステアリン酸ソルビタン、セスキステアリン酸ソルビタン、トリステアリン酸ソルビタン、モノイソステアリン酸グリセリル、モノミリスチン酸グリセリル、モノステアリン酸グリセリル、ポリオキシエチレン硬化ヒマシ油１０、ポリソルベート６０）、脂肪酸（ステアリン酸、ミリスチン酸、パルミチン酸、ベヘン酸、オレイン酸、リノール酸）、炭化水素油（白色ワセリン、流動パラフィン）、セトステアリルアルコール、及びポリオキシエチレン・ステアリルアルコール混合物を所定量混合し、８０℃で加熱溶解することにより、油相用組成物を調製した。また、別途、尿素、サリチル酸、グリシン、トリエタノールアミン及び水を所定量混合することにより、水相用組成物を調製した。次いで、８０℃に加熱した水相用組成物を、８０℃に加熱している油相用組成物に徐々に添加し混合して乳化操作を行い、外用乳化組成物（クリーム状の水中油型乳化製剤）を得た。製造直後の外用乳化組成物は、いずれも相分離を生じていない乳化形態であった。 Test Example 1
An external emulsified composition (creamy oil-in-water emulsified preparation) having the compositions shown in Tables 1 and 2 was prepared. Specifically, first, surfactants (sorbitan monostearate, sorbitan sesquistearate, sorbitan tristearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monostearate, polyoxyethylene hydrogenated castor oil 10, polysorbate). 60), fatty acid (stearic acid, myristic acid, palmitic acid, behenic acid, oleic acid, linoleic acid), hydrocarbon oil (white vaseline, liquid paraffin), cetostearyl alcohol, and polyoxyethylene / stearyl alcohol mixture in a predetermined amount. A composition for an oil phase was prepared by mixing and heating and dissolving at 80 ° C. Separately, a predetermined amount of urea, salicylic acid, glycine, triethanolamine and water were mixed to prepare a composition for an aqueous phase. Next, the aqueous phase composition heated to 80 ° C. is gradually added to the oil phase composition heated to 80 ° C., mixed and emulsified, and the external emulsified composition (creamy oil-in-water mold) is performed. Emulsified preparation) was obtained. The external emulsified compositions immediately after production were all in an emulsified form in which phase separation did not occur.
表１及び２に示す組成の外用乳化組成物（クリーム状の水中油型乳化製剤）を調製した。具体的には、先ず、界面活性剤（モノステアリン酸ソルビタン、セスキステアリン酸ソルビタン、トリステアリン酸ソルビタン、モノイソステアリン酸グリセリル、モノミリスチン酸グリセリル、モノステアリン酸グリセリル、ポリオキシエチレン硬化ヒマシ油１０、ポリソルベート６０）、脂肪酸（ステアリン酸、ミリスチン酸、パルミチン酸、ベヘン酸、オレイン酸、リノール酸）、炭化水素油（白色ワセリン、流動パラフィン）、セトステアリルアルコール、及びポリオキシエチレン・ステアリルアルコール混合物を所定量混合し、８０℃で加熱溶解することにより、油相用組成物を調製した。また、別途、尿素、サリチル酸、グリシン、トリエタノールアミン及び水を所定量混合することにより、水相用組成物を調製した。次いで、８０℃に加熱した水相用組成物を、８０℃に加熱している油相用組成物に徐々に添加し混合して乳化操作を行い、外用乳化組成物（クリーム状の水中油型乳化製剤）を得た。製造直後の外用乳化組成物は、いずれも相分離を生じていない乳化形態であった。 Test Example 1
An external emulsified composition (creamy oil-in-water emulsified preparation) having the compositions shown in Tables 1 and 2 was prepared. Specifically, first, surfactants (sorbitan monostearate, sorbitan sesquistearate, sorbitan tristearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monostearate, polyoxyethylene hydrogenated castor oil 10, polysorbate). 60), fatty acid (stearic acid, myristic acid, palmitic acid, behenic acid, oleic acid, linoleic acid), hydrocarbon oil (white vaseline, liquid paraffin), cetostearyl alcohol, and polyoxyethylene / stearyl alcohol mixture in a predetermined amount. A composition for an oil phase was prepared by mixing and heating and dissolving at 80 ° C. Separately, a predetermined amount of urea, salicylic acid, glycine, triethanolamine and water were mixed to prepare a composition for an aqueous phase. Next, the aqueous phase composition heated to 80 ° C. is gradually added to the oil phase composition heated to 80 ° C., mixed and emulsified, and the external emulsified composition (creamy oil-in-water mold) is performed. Emulsified preparation) was obtained. The external emulsified compositions immediately after production were all in an emulsified form in which phase separation did not occur.
得られた各外用乳化組成物について、乳化状態の安定性、及び尿素の安定性について、以下の方法で評価した。
For each of the obtained external emulsified compositions, the stability of the emulsified state and the stability of urea were evaluated by the following methods.
＜乳化状態の安定性＞
調製直後の各外用乳化組成物１６ｇを２０ｍｌ容のガラス瓶に充填し、５０℃の遮光条件で１カ月間保存した。１カ月間保存後の各外用乳化組成物の外観を目視にて観察し、「相分離が認められず、調製直後と同じ乳化状態を維持している状態」を１５点、「相分離が認められ、乳化状態を安定に維持できておらず、振っても均一にならない状態」を１点として、乳化状態の安定性の程度を１～１５点の間で評点化した。なお、参考のため、１点及び１５点と評価される各外用乳化組成物の外観を図１に示す。 <Stability in emulsified state>
16 g of each external emulsified composition immediately after preparation was filled in a 20 ml glass bottle and stored for 1 month under a light-shielded condition of 50 ° C. The appearance of each external emulsified composition after storage for 1 month was visually observed, and 15 points were "a state in which phase separation was not observed and the same emulsified state as immediately after preparation was maintained", and "phase separation was observed". The degree of stability of the emulsified state was scored between 1 and 15 points, with 1 point being "a state in which the emulsified state could not be stably maintained and was not uniform even when shaken." For reference, FIG. 1 shows the appearance of each external emulsified composition evaluated as 1 point and 15 points.
調製直後の各外用乳化組成物１６ｇを２０ｍｌ容のガラス瓶に充填し、５０℃の遮光条件で１カ月間保存した。１カ月間保存後の各外用乳化組成物の外観を目視にて観察し、「相分離が認められず、調製直後と同じ乳化状態を維持している状態」を１５点、「相分離が認められ、乳化状態を安定に維持できておらず、振っても均一にならない状態」を１点として、乳化状態の安定性の程度を１～１５点の間で評点化した。なお、参考のため、１点及び１５点と評価される各外用乳化組成物の外観を図１に示す。 <Stability in emulsified state>
16 g of each external emulsified composition immediately after preparation was filled in a 20 ml glass bottle and stored for 1 month under a light-shielded condition of 50 ° C. The appearance of each external emulsified composition after storage for 1 month was visually observed, and 15 points were "a state in which phase separation was not observed and the same emulsified state as immediately after preparation was maintained", and "phase separation was observed". The degree of stability of the emulsified state was scored between 1 and 15 points, with 1 point being "a state in which the emulsified state could not be stably maintained and was not uniform even when shaken." For reference, FIG. 1 shows the appearance of each external emulsified composition evaluated as 1 point and 15 points.
＜尿素の安定性＞
調製直後の各外用乳化組成物１６ｇを２０ｍｌ容のガラス瓶に充填し、５０℃の遮光条件で２カ月間保存した。保存前と２カ月保存後の各外用乳化組成物における尿素濃度をＨＰＬＣにて定量し、保存前の尿素濃度を１００％として２カ月保存後の尿素の残存率（％）の小数点第一位を四捨五入した値を算出した。２カ月保存後の尿素の残存率（％）の値を以下の判定基準に従って分類した。
・判定基準
◎：尿素の残存率が９８～１００％
○：尿素の残存率が９５～９７％
△：尿素の残存率が９２～９４％
×：尿素の残存率が９１％以下 <Urea stability>
16 g of each external emulsified composition immediately after preparation was filled in a 20 ml glass bottle and stored for 2 months under a light-shielded condition of 50 ° C. The urea concentration in each external emulsified composition before and after storage for 2 months is quantified by HPLC, and the urea concentration before storage is set to 100%, and the residual rate (%) of urea after storage for 2 months is set to the first decimal place. The rounded value was calculated. The value of the residual rate (%) of urea after storage for 2 months was classified according to the following criteria.
・ Judgment criteria ◎: Urea residual rate is 98-100%
◯: Urea residual rate is 95 to 97%
Δ: Urea residual rate is 92 to 94%
×: Urea residual rate is 91% or less
調製直後の各外用乳化組成物１６ｇを２０ｍｌ容のガラス瓶に充填し、５０℃の遮光条件で２カ月間保存した。保存前と２カ月保存後の各外用乳化組成物における尿素濃度をＨＰＬＣにて定量し、保存前の尿素濃度を１００％として２カ月保存後の尿素の残存率（％）の小数点第一位を四捨五入した値を算出した。２カ月保存後の尿素の残存率（％）の値を以下の判定基準に従って分類した。
・判定基準
◎：尿素の残存率が９８～１００％
○：尿素の残存率が９５～９７％
△：尿素の残存率が９２～９４％
×：尿素の残存率が９１％以下 <Urea stability>
16 g of each external emulsified composition immediately after preparation was filled in a 20 ml glass bottle and stored for 2 months under a light-shielded condition of 50 ° C. The urea concentration in each external emulsified composition before and after storage for 2 months is quantified by HPLC, and the urea concentration before storage is set to 100%, and the residual rate (%) of urea after storage for 2 months is set to the first decimal place. The rounded value was calculated. The value of the residual rate (%) of urea after storage for 2 months was classified according to the following criteria.
・ Judgment criteria ◎: Urea residual rate is 98-100%
◯: Urea residual rate is 95 to 97%
Δ: Urea residual rate is 92 to 94%
×: Urea residual rate is 91% or less
結果を表１及び２に示す。尿素を単独で含む外用乳化組成物では、保存による相分離は生じておらず、尿素の分解も抑制されていた（参考例１）。一方、尿素及びサリチル酸を含む外用乳化組成物では、保存による相分離が顕著に生じており、尿素の分解も認められた（比較例１～４）。また、尿素とサリチル酸と共に、親油性界面活性剤（ポリオキシエチレン硬化ヒマシ油１０）と炭素数１４以上の不飽和脂肪酸を組み合わせて配合しても、保存による相分離と尿素の分解を抑制できていなかった（比較例３及び４）。
The results are shown in Tables 1 and 2. In the external emulsified composition containing urea alone, phase separation did not occur due to storage, and the decomposition of urea was also suppressed (Reference Example 1). On the other hand, in the external emulsified composition containing urea and salicylic acid, phase separation due to storage was remarkable, and decomposition of urea was also observed (Comparative Examples 1 to 4). Further, even if a lipophilic surfactant (polyoxyethylene hydrogenated castor oil 10) and an unsaturated fatty acid having 14 or more carbon atoms are combined in combination with urea and salicylic acid, phase separation and decomposition of urea due to storage can be suppressed. No (Comparative Examples 3 and 4).
これに対して、尿素とサリチル酸と共に、親油性界面活性剤と炭素数１４以上の飽和脂肪酸を含む外用乳化組成物では、保存による相分離と尿素の分解を十分に抑制できていた（実施例１～１２）。特に、親油性界面活性剤として、モノステアリン酸ソルビタンを使用した場合には、保存による相分離を格段顕著に抑制できていた（実施例５及び１１）。更に、グリシンを含まない場合には、保存による尿素の分解を格段顕著に抑制できていた（実施例１１及び１２）。また、比較例１～４の各外用乳化組成物におけるサリチル酸をサリチル酸エチル又はサリチル酸メチルに変更した外用乳化組成物を調製し、試験例１と同じ方法で乳化状態、及び尿素の安定性を評価したところ、これに対応する比較例１～４と同程度の相分離と尿素の分解が生じていた。これに対し、実施例１～１２の各外用組成物におけるサリチル酸をサリチル酸エチル又はサリチル酸メチルに変更した各外用乳化組成物を調製し、試験例１と同じ方法で乳化状態、及び尿素安定性を評価したところ、これに対応する実施例１～１２と同程度に相分離及び尿素の分解が抑制できていた。
On the other hand, in the external emulsified composition containing a lipophilic surfactant and a saturated fatty acid having 14 or more carbon atoms together with urea and salicylic acid, phase separation and decomposition of urea due to storage could be sufficiently suppressed (Example 1). ~ 12). In particular, when sorbitan monostearate was used as the lipophilic surfactant, phase separation due to storage could be remarkably suppressed (Examples 5 and 11). Furthermore, when glycine was not contained, the decomposition of urea due to storage could be remarkably suppressed (Examples 11 and 12). In addition, an external emulsified composition in which salicylic acid in each of the external emulsified compositions of Comparative Examples 1 to 4 was changed to ethyl salicylate or methyl salicylate was prepared, and the emulsified state and the stability of urea were evaluated by the same method as in Test Example 1. However, the same degree of phase separation and decomposition of urea as in Comparative Examples 1 to 4 corresponding to this occurred. On the other hand, each external emulsified composition in which salicylic acid in each of the external compositions of Examples 1 to 12 was changed to ethyl salicylate or methyl salicylate was prepared, and the emulsified state and urea stability were evaluated by the same method as in Test Example 1. As a result, phase separation and decomposition of urea could be suppressed to the same extent as in Examples 1 to 12 corresponding to this.
処方例
表３に示す組成の外用乳化組成物（クリーム状の水中油型乳化製剤）を調製した。試験例１と同じ方法で、乳化状態、及び尿素の安定性を評価した。処方例１～９の外用乳化組成物はいずれも保存による相分離と尿素の分解を十分に抑制できていた。 An external emulsification composition (creamy oil-in-water emulsified preparation) having the composition shown in Table 3 of the formulation example was prepared. The emulsified state and the stability of urea were evaluated by the same method as in Test Example 1. All of the external emulsified compositions of Formulation Examples 1 to 9 were able to sufficiently suppress the phase separation and the decomposition of urea by storage.
表３に示す組成の外用乳化組成物（クリーム状の水中油型乳化製剤）を調製した。試験例１と同じ方法で、乳化状態、及び尿素の安定性を評価した。処方例１～９の外用乳化組成物はいずれも保存による相分離と尿素の分解を十分に抑制できていた。 An external emulsification composition (creamy oil-in-water emulsified preparation) having the composition shown in Table 3 of the formulation example was prepared. The emulsified state and the stability of urea were evaluated by the same method as in Test Example 1. All of the external emulsified compositions of Formulation Examples 1 to 9 were able to sufficiently suppress the phase separation and the decomposition of urea by storage.
Claims (3)
- (A)尿素、(B)サリチル酸系抗炎症剤、(C)炭素数１４以上の飽和脂肪酸及び／又はその塩、並びに(D)親油性界面活性剤を含む、外用乳化組成物。 An external emulsified composition containing (A) urea, (B) a salicylic acid-based anti-inflammatory agent, (C) a saturated fatty acid having 14 or more carbon atoms and / or a salt thereof, and (D) a lipophilic surfactant.
- 前記(D)成分が、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、及びポリオキシエチレン硬化ヒマシ油よりなる群から選択される少なくとも１種である、請求項１に記載の外用乳化組成物。 The external emulsification composition according to claim 1, wherein the component (D) is at least one selected from the group consisting of a sorbitan fatty acid ester, a glycerin fatty acid ester, and a polyoxyethylene hydrogenated castor oil.
- グリシンを含まない、請求項１又は２に記載の外用乳化組成物。 The external emulsified composition according to claim 1 or 2, which does not contain glycine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2020-207444 | 2020-12-15 | ||
| JP2020207444A JP2022094516A (en) | 2020-12-15 | 2020-12-15 | External emulsification composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022131080A1 true WO2022131080A1 (en) | 2022-06-23 |
Family
ID=82057738
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2021/044975 WO2022131080A1 (en) | 2020-12-15 | 2021-12-07 | Emulsified composition for external use |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP2022094516A (en) |
| TW (1) | TW202228713A (en) |
| WO (1) | WO2022131080A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005263660A (en) * | 2004-03-17 | 2005-09-29 | Shiseido Co Ltd | Urea-containing external preparation for skin |
| JP2010189351A (en) * | 2009-02-20 | 2010-09-02 | Shiseido Co Ltd | Transdermal absorption promoting agent and external preparation for skin containing the same |
-
2020
- 2020-12-15 JP JP2020207444A patent/JP2022094516A/en active Pending
-
2021
- 2021-11-23 TW TW110143583A patent/TW202228713A/en unknown
- 2021-12-07 WO PCT/JP2021/044975 patent/WO2022131080A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005263660A (en) * | 2004-03-17 | 2005-09-29 | Shiseido Co Ltd | Urea-containing external preparation for skin |
| JP2010189351A (en) * | 2009-02-20 | 2010-09-02 | Shiseido Co Ltd | Transdermal absorption promoting agent and external preparation for skin containing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| TW202228713A (en) | 2022-08-01 |
| JP2022094516A (en) | 2022-06-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI806867B (en) | Emulsion composition | |
| WO2022131080A1 (en) | Emulsified composition for external use | |
| JP2005239678A (en) | Creamy preparation for external use having improved retainability in horny layer | |
| WO2022131081A1 (en) | Emulsified composition for external application | |
| JP6967369B2 (en) | Emulsifying composition | |
| JP7092494B2 (en) | Water-in-oil emulsification composition | |
| JP2004189693A (en) | O/w-type emulsion cosmetic | |
| JP4285859B2 (en) | W / O / W type composite emulsion | |
| JP3803595B2 (en) | Urea-containing external composition for skin | |
| JP2005350379A (en) | Method for stabilizing prednisolone valerate acetate and excellently stable skin care preparation for external use comprising prednisolone valerate acetate | |
| JP2007153771A (en) | Emulsified composition for skin care | |
| WO2022131082A1 (en) | Pharmaceutical composition for external use | |
| JP2021001138A (en) | External composition | |
| JP7584886B2 (en) | Emulsion composition | |
| JP2020059665A (en) | Aqueous external pharmaceutical composition | |
| JP2020105091A (en) | External emulsion composition | |
| JP4521899B2 (en) | Clotamiton-containing skin external solution | |
| JP7465066B2 (en) | Emulsion stabilizer | |
| WO2022131083A1 (en) | External pharmaceutical composition | |
| JP7270374B2 (en) | external composition | |
| JP7282516B2 (en) | External emulsion composition | |
| JP7499024B2 (en) | External Composition | |
| JP2022096992A (en) | External pharmaceutical composition | |
| JP2022178158A (en) | external composition | |
| JP2023090338A (en) | emulsion composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21906443 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 21906443 Country of ref document: EP Kind code of ref document: A1 |