JP4430889B2 - Preparations for topical skin containing sparingly soluble materials - Google Patents
Preparations for topical skin containing sparingly soluble materials Download PDFInfo
- Publication number
- JP4430889B2 JP4430889B2 JP2003130921A JP2003130921A JP4430889B2 JP 4430889 B2 JP4430889 B2 JP 4430889B2 JP 2003130921 A JP2003130921 A JP 2003130921A JP 2003130921 A JP2003130921 A JP 2003130921A JP 4430889 B2 JP4430889 B2 JP 4430889B2
- Authority
- JP
- Japan
- Prior art keywords
- skin
- external preparation
- soluble material
- matrix
- alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000002360 preparation method Methods 0.000 title claims description 53
- 239000002195 soluble material Substances 0.000 title claims description 41
- 230000000699 topical effect Effects 0.000 title 1
- -1 aliphatic saturated alcohol Chemical class 0.000 claims description 52
- 239000011159 matrix material Substances 0.000 claims description 28
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 24
- 239000000194 fatty acid Substances 0.000 claims description 24
- 229930195729 fatty acid Natural products 0.000 claims description 24
- 239000004973 liquid crystal related substance Substances 0.000 claims description 19
- 239000004094 surface-active agent Substances 0.000 claims description 15
- WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 150000001298 alcohols Chemical class 0.000 claims description 14
- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 claims description 14
- 229940096998 ursolic acid Drugs 0.000 claims description 14
- 229930182470 glycoside Natural products 0.000 claims description 13
- 150000002338 glycosides Chemical class 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 9
- 229920000223 polyglycerol Polymers 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 150000007513 acids Chemical class 0.000 claims description 7
- 150000005846 sugar alcohols Polymers 0.000 claims description 7
- 238000010790 dilution Methods 0.000 claims description 6
- 239000012895 dilution Substances 0.000 claims description 6
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 claims description 6
- 150000002515 isoflavone derivatives Chemical class 0.000 claims description 6
- 235000008696 isoflavones Nutrition 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000008365 aqueous carrier Substances 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 239000000470 constituent Substances 0.000 claims description 4
- HBGGXOJOCNVPFY-UHFFFAOYSA-N diisononyl phthalate Chemical compound CC(C)CCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCC(C)C HBGGXOJOCNVPFY-UHFFFAOYSA-N 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- LFVLUOAHQIVABZ-UHFFFAOYSA-N Iodofenphos Chemical compound COP(=S)(OC)OC1=CC(Cl)=C(I)C=C1Cl LFVLUOAHQIVABZ-UHFFFAOYSA-N 0.000 claims description 2
- 241000023320 Luma <angiosperm> Species 0.000 claims description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 claims description 2
- 238000010792 warming Methods 0.000 claims description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- 239000000126 substance Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- GZIFEOYASATJEH-VHFRWLAGSA-N δ-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-VHFRWLAGSA-N 0.000 description 10
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 7
- 239000002537 cosmetic Substances 0.000 description 7
- 235000011187 glycerol Nutrition 0.000 description 7
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 7
- 229960005323 phenoxyethanol Drugs 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 229960000541 cetyl alcohol Drugs 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical group CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 5
- GZIFEOYASATJEH-UHFFFAOYSA-N D-delta tocopherol Natural products OC1=CC(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-UHFFFAOYSA-N 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 241000209140 Triticum Species 0.000 description 5
- 235000021307 Triticum Nutrition 0.000 description 5
- 235000010389 delta-tocopherol Nutrition 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002446 δ-tocopherol Substances 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 229940121375 antifungal agent Drugs 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 150000004665 fatty acids Chemical group 0.000 description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 3
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 239000012965 benzophenone Substances 0.000 description 3
- 150000008366 benzophenones Chemical class 0.000 description 3
- 239000003240 coconut oil Substances 0.000 description 3
- 235000019864 coconut oil Nutrition 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical group CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 3
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid ester group Chemical group C(CCCCCCCCCCC)(=O)O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 229960002568 ethinylestradiol Drugs 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 150000003648 triterpenes Chemical class 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
- LEEDMQGKBNGPDN-UHFFFAOYSA-N 2-methylnonadecane Chemical compound CCCCCCCCCCCCCCCCCC(C)C LEEDMQGKBNGPDN-UHFFFAOYSA-N 0.000 description 2
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- XPFCZYUVICHKDS-UHFFFAOYSA-N 3-methylbutane-1,3-diol Chemical compound CC(C)(O)CCO XPFCZYUVICHKDS-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 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
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 229940092705 beclomethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 2
- 229960002537 betamethasone Drugs 0.000 description 2
- 239000002327 cardiovascular agent Substances 0.000 description 2
- 229940125692 cardiovascular agent Drugs 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229940105990 diglycerin Drugs 0.000 description 2
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 239000010445 mica Substances 0.000 description 2
- 229910052618 mica group Inorganic materials 0.000 description 2
- 229960001783 nicardipine Drugs 0.000 description 2
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 2
- 229960001597 nifedipine Drugs 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- UBFZCDAKYBGKGF-UHFFFAOYSA-N octadecanoic acid propane-1,2,3-triol Chemical compound OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)CO.CCCCCCCCCCCCCCCCCC(O)=O UBFZCDAKYBGKGF-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 2
- 229960001173 oxybenzone Drugs 0.000 description 2
- WCVRQHFDJLLWFE-UHFFFAOYSA-N pentane-1,2-diol Chemical compound CCCC(O)CO WCVRQHFDJLLWFE-UHFFFAOYSA-N 0.000 description 2
- 229940068065 phytosterols Drugs 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- KZJWDPNRJALLNS-VPUBHVLGSA-N (-)-beta-Sitosterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@@H](C(C)C)CC)C)CC4)CC3)CC=2)CC1 KZJWDPNRJALLNS-VPUBHVLGSA-N 0.000 description 1
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 1
- CSVWWLUMXNHWSU-UHFFFAOYSA-N (22E)-(24xi)-24-ethyl-5alpha-cholest-22-en-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 CSVWWLUMXNHWSU-UHFFFAOYSA-N 0.000 description 1
- FWNZEKQVBDXWKA-ZCWREFTMSA-N (2r,5s)-2-[[(3s,8s,9s,10r,13r,14s,17r)-17-[(2r,5r)-5,6-dimethylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CC[C@@H](C)C(C)C)[C@@H]1OC(CO)[C@@H](O)C(O)C1O FWNZEKQVBDXWKA-ZCWREFTMSA-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
- JWQKMEKSFPNAIB-UHFFFAOYSA-N 1-methyl-5-prop-1-en-2-ylcyclohexene Chemical compound CC(=C)C1CCC=C(C)C1 JWQKMEKSFPNAIB-UHFFFAOYSA-N 0.000 description 1
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-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
- ZONJATNKKGGVSU-UHFFFAOYSA-N 14-methylpentadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCC(O)=O ZONJATNKKGGVSU-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- DVVXXHVHGGWWPE-UHFFFAOYSA-N 2-(dimethylamino)benzoic acid Chemical class CN(C)C1=CC=CC=C1C(O)=O DVVXXHVHGGWWPE-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- GECRRQVLQHRVNH-MRCUWXFGSA-N 2-octyldodecyl (z)-octadec-9-enoate Chemical compound CCCCCCCCCCC(CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC GECRRQVLQHRVNH-MRCUWXFGSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- KLEXDBGYSOIREE-UHFFFAOYSA-N 24xi-n-propylcholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CCC)C(C)C)C1(C)CC2 KLEXDBGYSOIREE-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- OEOIWYCWCDBOPA-UHFFFAOYSA-N 6-methyl-heptanoic acid Chemical compound CC(C)CCCCC(O)=O OEOIWYCWCDBOPA-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- SGNBVLSWZMBQTH-FGAXOLDCSA-N Campesterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@H](C(C)C)C)C)CC4)CC3)CC=2)CC1 SGNBVLSWZMBQTH-FGAXOLDCSA-N 0.000 description 1
- LPZCCMIISIBREI-MTFRKTCUSA-N Citrostadienol Natural products CC=C(CC[C@@H](C)[C@H]1CC[C@H]2C3=CC[C@H]4[C@H](C)[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C LPZCCMIISIBREI-MTFRKTCUSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- XMSXQFUHVRWGNA-UHFFFAOYSA-N Decamethylcyclopentasiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1 XMSXQFUHVRWGNA-UHFFFAOYSA-N 0.000 description 1
- ARVGMISWLZPBCH-UHFFFAOYSA-N Dehydro-beta-sitosterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CC=C21 ARVGMISWLZPBCH-UHFFFAOYSA-N 0.000 description 1
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 description 1
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 1
- BTEISVKTSQLKST-UHFFFAOYSA-N Haliclonasterol Natural products CC(C=CC(C)C(C)(C)C)C1CCC2C3=CC=C4CC(O)CCC4(C)C3CCC12C BTEISVKTSQLKST-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 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
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- NPJICTMALKLTFW-NEOYQNEMSA-N Sitosteryl glucoside Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CC[C@@H](CC)C(C)C)[C@@H]1OC(CO)[C@@H](O)C(O)C1O NPJICTMALKLTFW-NEOYQNEMSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 230000006750 UV protection Effects 0.000 description 1
- AWNFRSYMBMFGLK-UHFFFAOYSA-N [2,2-dimethyl-3-(16-methylheptadecanoyloxy)propyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(C)(C)COC(=O)CCCCCCCCCCCCCCC(C)C AWNFRSYMBMFGLK-UHFFFAOYSA-N 0.000 description 1
- 230000037374 absorbed through the skin Effects 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000637 arginyl group Chemical class N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 239000010426 asphalt Substances 0.000 description 1
- IRERQBUNZFJFGC-UHFFFAOYSA-L azure blue Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[S-]S[S-].[O-][Si]([O-])([O-])[O-].[O-][Si]([O-])([O-])[O-].[O-][Si]([O-])([O-])[O-].[O-][Si]([O-])([O-])[O-].[O-][Si]([O-])([O-])[O-].[O-][Si]([O-])([O-])[O-] IRERQBUNZFJFGC-UHFFFAOYSA-L 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229940116226 behenic acid Drugs 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- FUFAPKOCRZYSHH-CVTBAMPXSA-N benzyl (1s,2r,4as,6ar,6as,6br,8ar,10s,12ar,14bs)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1h-picene-4a-carboxylate Chemical compound O=C([C@]12CC[C@H]([C@@H]([C@H]1C=1[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3CC=1)C)(C)CC2)C)C)OCC1=CC=CC=C1 FUFAPKOCRZYSHH-CVTBAMPXSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- MJVXAPPOFPTTCA-UHFFFAOYSA-N beta-Sistosterol Natural products CCC(CCC(C)C1CCC2C3CC=C4C(C)C(O)CCC4(C)C3CCC12C)C(C)C MJVXAPPOFPTTCA-UHFFFAOYSA-N 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- QXMNTPFFZFYQAI-IMDKZJJXSA-N beta-sitosterol 3-O-beta-D-glucopyranoside Natural products CC[C@H](CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@H](CC[C@]4(C)[C@H]3CC[C@]12C)O[C@@H]5C[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O)C(C)C QXMNTPFFZFYQAI-IMDKZJJXSA-N 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- SGNBVLSWZMBQTH-PODYLUTMSA-N campesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](C)C(C)C)[C@@]1(C)CC2 SGNBVLSWZMBQTH-PODYLUTMSA-N 0.000 description 1
- 235000000431 campesterol Nutrition 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229940086555 cyclomethicone Drugs 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 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
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
- 229960001348 estriol Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 description 1
- 229940051250 hexylene glycol Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229940100540 neopentyl glycol diisostearate Drugs 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229940100243 oleanolic acid Drugs 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 235000002378 plant sterols Nutrition 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 229930002330 retinoic acid Natural products 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
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 235000015500 sitosterol Nutrition 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical group CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 229940054870 urso Drugs 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 150000003675 ursolic acids Chemical class 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
- 239000011782 vitamin Substances 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
【０００１】
【発明の属する技術分野】
本発明は、化粧料或いは皮膚外用医薬などの皮膚外用剤において、難溶性の素材の生体利用性を高めるのに有益な皮膚外用製剤に関する。
【０００２】
【従来の技術】
医薬或いは化粧料などの、生体への作用を必須構成要素とする組成物に於いて、該生体への作用を担う物質の中には、水溶性或いは油溶性の低い物質、即ち、難溶性の素材が少なくない。例えば、医薬品であれば、ニフェジピン、ニカルジピン等のジヒドロピリジン系循環器用薬、ベンジルアミン系の抗真菌剤、イミダゾール系の抗真菌剤、インドメタシンなどのノンステロイド抗炎症剤類、ベタメタゾンやベクロメタゾンなどのステロイド系抗炎症剤等の複素環化合物類、化粧品であれば、オキシベンゾンなどのようなベンゾフェノン類、エチニルエストラジオールなどのステロイド類などの複素環化合物、フィトステサイド等のように疎水性の母核を有する物質の配糖体、ウルソール酸、ウルソール酸の塩或いはウルソール酸の芳香族エステル等のトリテルペンとその誘導体などがこの難溶性の素材に該当する。又、これらの物質を含む生薬の有機溶剤による抽出物であって、難溶性を示すものもかかる難溶性物質に該当する。これらの素材は、何れも、一様に溶解した溶液系では優れた作用を発揮するが、通常の乳化系等では、結晶或いは固体の微細分散形態をとり、この為、本来有している作用を発揮できない場合が少なくなかった。即ち、その溶解度の低さという、物理化学的性質故にその有効性が著しく減じられていたと言える。この為、かかる素材の生体利用性を向上させる試みが種々なされている。この様な試みには、例えば、ポリオキシエチレン基が６０モル以上の非イオン界面活性剤を用いて、前記素材を微細な粒子にして分散させる方法（特許文献１）、水分散性のあるポリマーとともにマトリックスを作成し、ポリマーミセルを形成させる方法（特許文献２）或いはトリエチレングリコールとＣ４〜６の二価アルコールなどの溶解性の高いベヒクルを共存させて、その溶剤効果に依存する方法（特許文献３）等が知られている。しかしながら、これらの方法に於いてもその効果は充分ではなく、この様な系においては時として素材の結晶が析出するような場合があり、安定性の面からもその改善が望まれていた。
【０００３】
一方、炭素数１２〜２４の脂肪族飽和アルコール或いはフィトステロールを難溶性の素材と組み合わせる技術としては、この様なアルコール類でコートして難溶性の素材の苦味を減じる方法がしられているが、これを難溶性の素材とともに使用してマトリックスを作り、これにより生体利用性を向上させる試みは為されていない。難溶性の素材に対して、１〜５倍量の次に挙げるアルコール類を含有するマトリックスと言う構成も全く知られていないし、この様な構成を取ることにより難溶性の素材の生体利用性を著しく高めることが出来ることも全く知られていない。
【０００４】
【特許文献１】
特開２００１−１２２７６７号公報
【特許文献２】
特開２００１−２２６２９４号公報
【特許文献３】
特開２０００−３２７５８８号公報
【０００５】
【発明が解決しようとする課題】
本発明は、この様な状況下為されたものであり、皮膚外用剤において、難溶性の素材の生体利用性を高める手段を提供することを課題とする。
【０００６】
【課題の解決手段】
この様な状況に鑑みて、本発明者らは、皮膚外用剤において、難溶性の素材の生体利用性を高める手段を求めて、鋭意研究努力を重ねた結果、難溶性の素材を含有する皮膚外用剤用の製剤であって、前記難溶性の素材に対して、１〜５倍量の、炭素数１２〜２４の脂肪族飽和アルコール、フィトステロール等のアルコール類を含有するマトリックスをベヒクルに分散してなる皮膚外用製剤がその様な性質を有していることを見出し、発明を完成させるに至った。即ち、本発明は、以下に示す技術に関するものである。
（１）下記に示す難溶性の素材から選択される１種乃至は２種以上と、前記難溶性の素材に対して、１〜５倍量の下記に挙げるアルコール類とを含有する、液晶を部分的に形成するマトリックスを分散してなる皮膚外用製剤であって、
１）前記難溶性の素材と前記アルコール類を含有するマトリックス構成成分を加温して相溶させ、
２）しかる後に、予め加温相溶させておいた、界面活性剤と多価アルコールを含有する、マトリックス構成成分以外の非水成分で、前記マトリックスを希釈し、希釈物とし、
３）該希釈物に、予め加温しておいた水性成分を加え、冷却することにより、製造されることを特徴とする、皮膚外用製剤。
（難溶性の素材）
フィトステロールの配糖体、イソフラボン、イソフラボンの配糖体、トリテルペン酸および／又はそれらの塩、トリテルペン酸の芳香族エステル
（アルコール類）
炭素数１２〜２４の脂肪族飽和アルコール、フィトステロール
（２）前記難溶性の素材が、フィトステロールの配糖体、ウルソール酸、ウルソール酸の塩及びウルソール酸の芳香族エステルから選択される１種乃至は２種以上である、（１）に記載の皮膚外用製剤。
（３）更に、ポリグリセリンの脂肪酸エステルを含有することを特徴とする、（１）又は（２）に記載の皮膚外用製剤。
（４）ポリグリセリンの脂肪酸エステルが、デカグリセリンのモノ脂肪酸エステルであることを特徴とする、（３）に記載の皮膚外用製剤。
（５） １）難溶性の素材とアルコール類を含有するマトリックス構成成分を加温して相溶させ、
２）しかる後に、予め加温相溶させておいた、界面活性剤と多価アルコールを含有する、マトリックス構成成分以外の非水成分で、希釈し、３）該希釈物に、予め加温しておいた水性成分を加え、冷却することを特徴とする、（１）〜（４）のいずれかに記載の皮膚外用製剤の製造方法。
（６）難溶性の素材とアルコール類を含有するマトリックス小滴の周囲に界面活性剤が配向し、水性担体に分散した形態であることを特徴とする、（５）に記載の製造方法。
（７）難溶性の素材とアルコール類を含有するマトリックス小滴の周囲に界面活性剤が配向し、水性担体に分散した形態であることを特徴とする、（１）〜（４）の何れかに記載の皮膚外用製剤。
【０００７】
【発明の実施の形態】
（１）本発明の皮膚外用製剤の必須成分である難溶性の素材
本発明の皮膚外用製剤では、難溶性の素材を必須成分として含有する。本発明で言う難溶性の素材とは、複素環化合物類、疎水性の母核を有する物質の配糖体又はトリテルペンとその誘導体であり、その基本的性質は、水に殆ど溶解せず、且つ、油性成分とも１気圧２０℃の条件では溶解しにくく、微細な結晶或いはアモルファス状の固形物を析出するような性質を有するものである。その皮膚外用剤に於ける配合目的は、保湿作用、清浄化作用、肌荒れ防止・改善作用、美白作用、紫外線防護作用、抗炎症作用である。具体的な化合物としては、医薬品においては、複素環化合物としてのニフェジピン、ニカルジピン等のジヒドロピリジン系循環器用薬、ベンジルアミン系の抗真菌剤、イミダゾール系の抗真菌剤、インドメタシンなどのノンステロイド抗炎症剤類、ベタメタゾンやベクロメタゾンなどのステロイド系抗炎症剤等、化粧品においては、複素環化合物としてのオキシベンゾンなどのようなベンゾフェノン類、エチニルエストラジオールなどのステロイド類など、疎水性の母核を有する物質の配糖体としてのフィトステサイド等、トリテルペンとその誘導体としての、ウルソール酸、ウルソール酸の塩或いはウルソール酸の芳香族エステル等が例示できる。又、これらの物質を含む生薬の有機溶剤による抽出物であって、難溶性を示すものもかかる難溶性物質に該当する。難溶性物質の好ましい具体例としては、カンペステロールグルコシド、シトステロールグルコシド、スティグマスタノールグルコシド、スティグマスタノールマルトシド等のフィトステロールの配糖体、ダイズエニン等のイソフラボン、ダイズイン等のイソフラボンの配糖体、オレアノール酸、アジア酸、ウルソール酸等のトリテルペン酸、それらのナトリウム塩、カリウム塩等のアルカリ金属塩、カルシウム、マグネシウム等のアルカリ土類金属塩、アンモニウム塩、トリエタノールアミン塩、トリエチルアミン塩等の有機アミン塩類、リジン塩、アルギニン塩等の塩基性アミノ酸塩等その塩及びベンジルエステル、フェネチルエステル等トリテルペン酸の芳香族エステルが好ましく例示でき、中でも、フィトステロールの配糖体、ウルソール酸、ウルソール酸の塩及びウルソール酸の芳香族エステルが例示できる。かかる成分は、適宜選択される１種乃至は２種以上を、その薬理作用に適した量を含有させる。具体的には、皮膚外用製剤全量に対して、総量で０．１〜１０重量％が好ましく、更に好ましくは０．２〜５重量％である。
【０００８】
（２）本発明の皮膚外用製剤の必須成分であるアルコール類
本発明の皮膚外用剤は、必須成分として、アルコール類を必須成分として含有する。該アルコール類としては、ラウリルアルコール、ミリスチルアルコール、セチルアルコール、ステアリルアルコール、ベヘニルアルコール、イソステアリルアルコール等の炭素数１２〜２４の脂肪族飽和アルコール、カンペステロール、スティグマスタノール、シトステロール等のフィトステロールが好適に例示できる。かかるアルコール類は、前記難溶性の素材とともに、液晶、固溶体、溶液状態等が混在する複合的なマトリックスを形成し、前記難溶性の素材の生体利用性を高める作用を発揮する。この様な作用を発揮する為には、アルコール類は、総量で、前記難溶性の素材の総量に対して、１〜５倍量含有させるのが好ましい。従って、皮膚外用製剤全量に対しては、０．１〜５０重量％が好ましく、０．２〜２５重量％が更に好ましい。
【０００９】
（３）本発明の皮膚外用製剤の好ましい成分であるポリグリセリンの脂肪酸エステル
本発明の皮膚外用製剤は、好ましい形態に於いて、ポリグリセリンの脂肪酸エステルを好ましい成分として含有することを特徴とする。ポリグリセリンの脂肪酸エステルとしては、親水性・親油性バランス（Ｈ．Ｌ．Ｂ．）が１０以上のものが好ましい。かかるポリグリセリンの脂肪酸エステルのポリグリセリン基としては、重合度が５以上であることが好ましく、特に好ましくは８〜１２である。又、脂肪酸残基としては、ラウリン酸残基、ミリスチン酸残基、パルミチン酸残基、ステアリン酸残基、ベヘン酸残基、イソステアリン酸残基、オレイン酸残基などの炭素数１２〜２４のものが特に好ましい。又、前記脂肪酸残基の数としては、遊離の水酸基の数より多い方が好ましく、好ましくは脂肪酸残基の数の５〜２０倍遊離の水酸基が存在することが好ましい。特に好ましいものとしては、具体的には、デカグリセリンモノステアレート（ＨＬＢ１３．５）、ペンタグリセリンモノステアレート（ＨＬＢ１１）、デカグリセリンイソステアレート（ＨＬＢ１３．５）、ペンタグリセリンモノイソステアレート（ＨＬＢ１１）、デカグリセリンモノオレート（ＨＬＢ１３）等が好ましく例示できる。かかる成分は、本発明の皮膚外用剤に於いて、親水性界面活性剤として作用する。ポリグリセリンの脂肪酸エステル類は水難溶性成分及びアルコール類とともに液晶構造を作りやすく、かかる液晶構造がマトリックスの少なくとも一部に生成された場合には、前記難溶性成分は経皮吸収されやすいマトリックスとして、皮膚上に存在するようになる。液晶を生成させやすい処理法としては、１）難溶性の素材とアルコール類を含有するマトリックス構成成分を加温して相溶させ、２）しかる後に、予め加温相溶させておいた、界面活性剤であるポリグリセリンの脂肪酸エステルと多価アルコールを含有する、マトリックス構成成分以外の非水成分で、希釈し、３）該希釈物に、予め加温しておいた水性成分を加え、冷却することが、好ましく例示できる。かかる成分は唯一種を含有することも出来るし、二種以上を組み合わせて含有することも出来る。本発明の皮膚外用剤に於ける、かかる成分の好ましい含有量は、総量で、皮膚外用剤全量に対して、０．１〜１０重量％であり、更に好ましくは１〜５重量部である。又、ポリグリセリンの脂肪酸エステルの量は、難溶性成分の総量に対して、７０〜３００重量％であることが好ましい。
【００１０】
（４）本発明の皮膚外用製剤
本発明の皮膚外用製剤は、１）難溶性の素材と、２）アルコール類とを含有し、ポリグリセリンの脂肪酸エステルを好ましい成分として含有し、前記難溶性塩がつくる液晶、溶液（溶解状態の部分）及び結晶が混在するマトリックスが分散した形態であることを特徴とする。これらの成分を用いて、液晶構造を含む製剤を製造するには、例えば、次のような処理を行うことが好ましく例示できる。１）難溶性の素材とアルコール類を含有するマトリックス構成成分を加温して相溶させ、２）しかる後に、予め加温相溶させておいた、界面活性剤であるポリグリセリンの脂肪酸エステルと多価アルコールを含有する、マトリックス構成成分以外の非水成分で、希釈し、３）該希釈物に、予め加温しておいた水性成分を加え、冷却する。前記希釈物を構成する難溶性の素材以外の非水成分としては、例えば、１，３−ブタンジオール、ジプレングリコール、グリセリン、ジグリセリン、イソプレングリコール、１，２−ペンタンジオール、１，２−ヘキシレングリコール等の多価アルコール類、フェノキシエタノール等の抗菌成分、ポリグリセリンの脂肪酸エステル以外の界面活性剤などが例示できる。ポリグリセリンの脂肪酸エステル以外の界面活性剤としては、非イオン性界面活性剤が好ましく例示でき、中でも、ポリオキシエチレン骨格を有しない界面活性剤が特に好適に例示できる。この様な界面活性剤としては、例えば、ショ糖脂肪酸エステル、ポリグリセリルポリオキシブチレンアルキル（アルケニル）エーテルが好ましく例示できる。ショ糖脂肪酸エステルには既に市販されているものが多数存在するのでそれらを利用することができる。ポリグリセリルポリオキシブチレンアルキル（アルケニル）エーテルは例えば、特開昭５９−１４０３に記載されている方法で製造することが出来る。即ち、高級アルコール、グリシドール及びテトラヒドロフランを、ルイス酸又はアルカリを触媒として反応させることにより得ることが出来る。ポリグリセリルポリオキシブチレンアルキル（アルケニル）エーテルにおけるグリセリル基の好ましい付加モル数は、５〜２５であり、更に好ましくは１０〜２０である。オキシブチレン基の好ましい付加モル数は、５〜２５であり、更に好ましくは１０〜２０である。又、アルキル（アルケニル）基としては、炭素数１０〜３０のものが好ましく、例えば、ラウリル基、セチル基、ステアリル基、オレイル基、イソステアリル基、ドデシルデシル基等が好適に例示できる。かかるポリグリセリルポリオキシブチレンアルキル（アルケニル）エーテルとしては、前記の如くに製造して用いることも出来るが、既に市販されているものがあり、この様な市販品を用いることも出来る。好ましい市販品としては、例えば、日光ケミカルズ株式会社より市販されている、「ハイグリオール−Ｓ２６」（ポリグリセリル（１３）ポリオキシブチレン（１４）ステアリルエーテル）が好ましく例示できる。かかるショ糖脂肪酸エステル、ポリグリセリルポリオキシブチレンアルキル（アルケニル）エーテルの好ましい含有量は、総量で、皮膚外用剤全量に対して、０．０５〜１０重量％であり、０．１〜５重量％が更に好ましい。
【００１１】
本発明の皮膚外用製剤では、前記本発明の効果を損なわない範囲において、通常化粧料或いは皮膚外用医薬のような皮膚外用剤で、通常使用される任意成分を、液晶生成成分の相、液晶生成成分以外の非水成分の相、水の相の何れかの相に分けて、含有させることが出来る。かかる任意成分としては、例えば、スクワラン、流動パラフィン、軽質流動イソパラフィン、重質流動イソパラフィン、マイクロクリスタリンワックス、固形パラフィンなどの炭化水素類、ジメチコン、フェメチコン、シクロメチコン、アモジメチコン、ポリエーテル変性シリコーンなどのシリコーン類、ホホバ油、カルナウバワックス、モクロウ、ミツロウ、ゲイロウ、オレイン酸オクチルドデシル、イソプロピルミリステート、ネオペンチルグリコールジイソステアレート、リンゴ酸ジイソステアレートなどのエステル類、ステアリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、イソステアリン酸、イソパルミチン酸、ベヘン酸、オレイン酸などの脂肪酸類、ヒマシ油、椰子油、水添椰子油、椿油、小麦胚芽油、イソステアリン酸トリグリセライド、イソオクタン酸トリグリセライド、オリーブオイル等のトリグリセライド類、１，３−ブタンジオール、グリセリン、ジグリセリン、ジプロピレングリコール、ポリエチレングリコール、１，２−ペンタンジオール、１，２−ヘキシレングリコール、イソプレングリコールなどの多価アルコール、結晶セルロースや架橋型メチルポリシロキサン、ポリエチレン粉末、アクリル樹脂粉体等の有機粉体類、タルク、マイカ、セリサイト、炭酸マグネシウム、炭酸カルシウム、二酸化チタン、酸化鉄、紺青、群青、チタンマイカ、チタンセリサイト、シリカ等の表面処理されていても良い粉体類、アクリル酸・メタクリル酸アルキルコポリマー及び／又はその塩、カルボキシビニルポリマー及び／又はその塩、キサンタンガムやヒドロキシプロピルセルロースなどの増粘剤、レチノール、レチノイン酸、トコフェロール、リボフラビン、ピリドキシン、アスコルビン酸、アスコルビン酸リン酸エステル塩などのビタミンやエストラジオール、エチニルエストラジオール、エストリオールなどのステロイド類などの有効成分、フェノキシエタノール、パラベン類、ヒビテングルコネート、塩化ベンザルコニウム等の防腐剤、ジメチルアミノ安息香酸エステル類、桂皮酸エステル類、ベンゾフェノン類などの紫外線吸収剤などが好ましく例示できる。尚、本発明の皮膚外用製剤は、化粧料用の製剤、皮膚外用医薬品の製剤の何れの製剤としても適用できるが、化粧料に適用することが、特に好ましい。
【００１２】
【実施例】
以下に、実施例を挙げて、本発明について更に詳細に説明を加えるが、本発明がかかる実施例にのみ限定されないことは言うまでもない。
【００１３】
＜実施例１＞
以下に示す処方に従って、難溶性の素材として、スティグマスタノールマルトシド（植物性ステロールの配糖体）を含有する、本発明の皮膚外用製剤を作成した。即ち、イ、ロ及びハをそれぞれ９５℃に温調し、それぞれが一様になったことを確認した。イにロを加えて希釈し、更に、攪拌下これにハを徐々に加え、攪拌冷却し乳液状の本発明の皮膚外用製剤１を得た。このものを偏光顕微鏡下観察したところ、図３（図面代用写真）に示す如く、液晶を構造有する部分とそうでは無い部分とが混然と存在する小粒子が、一様に分散した形態であることがわかった。又、一様の状態になったイは液晶を部分的に形成していること、イにロを加えて希釈したものの状態は、溶液状態の部分と液晶とベヒクルが共存する多相状態であることもわかった。比較例１として、同じ処方成分を用いて、添加順序を変えて乳液を作成した。このものを偏光顕微鏡下観察しても、蛍光は認められず、液晶構造が存在していないことがわかった。これらの安定性（４０℃１ヶ月保存条件）も調べた。結果は、皮膚外用製剤１が安定に存在しているのに対して、比較例１は分離が認められ、液晶構造が部分的に存在するマトリックスを構成することにより安定性が向上することが確認された。
イ
小麦胚芽由来フィトステロール混合物 ２ 重量部
セタノール ５ 重量部
スティグマスタノールマルトシド ３ 重量部
δ−トコフェロール ０．１重量部
ロ
デカグリセリンモノステアレート ５ 重量部
ジプロピレングリコール １０ 重量部
グリセリン ５ 重量部
フェノキシエタノール １ 重量部
ハ
水 ６８．９重量部
（比較例１）
イ
小麦胚芽由来フィトステロール混合物 ２ 重量部
セタノール ５ 重量部
スティグマスタノールマルトシド ３ 重量部
δ−トコフェロール ０．１重量部
デカグリセリンモノステアレート ５ 重量部
フェノキシエタノール １ 重量部
ロ
ジプロピレングリコール １０ 重量部
グリセリン ５ 重量部
水 ６８．９重量部
製法）イ、ロをそれぞれ９５℃に温調し、攪拌下イに徐々にロを加え、攪拌下冷却し、乳化物を得た。
【００１４】
＜実施例２＞
実施例の皮膚外用製剤１と比較例１とを用いて、専門パネラーによる使用感の比較を行った。使用感はのびの良さ、塗布後のしっとり感の良さ、塗布後の肌のなめらかさで、スコア５：非常によい、スコア４：良い、スコア３：やや良い、スコア２：やや悪い、スコア１：悪いの基準で評価は行った。結果を表１に示す。これより、本発明の皮膚外用製剤が優れた使用感を有していることがわかる。又、この使用感の良さは、スティグマスタノールマルトシドを部分液晶が存在するマトリックス状態で分散されていることにあることがわかる。
【００１５】
【表１】
＜実施例３＞
皮膚外用製剤１と比較例１について、スティギング抑制作用を調べた。即ち、メチルパラベンに対して、閾値０．０１％でスティギングを感じる（メチルパラベン溶液を接触させると刺激を感じる最低濃度が０．０１％である）パネラーを用いて、下腕内側部に４ｃｍ×４ｃｍの部位を作成し、サンプル３０μｌを塗布して処理した後、各種濃度のメチルパラベン１０％ｉｎ１，３−ブタンジオール水溶液を綿棒に含浸させて接触させ、スティギングを感じる閾値を調べた。結果を表２に示す。これより、皮膚外用製剤１は比較例１に比して２０倍以上スティギングを抑制する作用を有することがわかる。（表中○はスティギングなし、×はスティギングあり、△はスティギングの有無が不明瞭）
【００１７】
【表２】
＜実施例４〜１０＞
皮膚外用剤１の難溶性の素材を変えて、液晶分散系が出来るか否かの検討を行った。結果を表３に示す。これより、何れの難溶性の素材も部分的に液晶が存在するマトリックス分散系を生成することがわかった。尚、製法は皮膚外用製剤１に準じた。
イ
小麦胚芽由来フィトステロール混合物 ２ 重量部
セタノール ５ 重量部
表３記載の難溶性の成分 ３ 重量部
δ−トコフェロール ０．１重量部
ロ
デカグリセリンモノステアレート ５ 重量部
ジプロピレングリコール １０ 重量部
グリセリン ５ 重量部
フェノキシエタノール １ 重量部
ハ
水 ６８．９重量部
【００１９】
【表３】
＜実施例１１〜１４＞
皮膚外用製剤１のデカグリセリンモノステアレートを他のポリグリセリン脂肪酸エステルに変えて、液晶分散系が出来るか否かの検討を行った。結果を表４に示す。これより、本発明の皮膚外用製剤では、ＨＬＢ１０以上のポリグリセリン脂肪酸エステルが何れも使用可能であることがわかる。
イ
小麦胚芽由来フィトステロール混合物 ２ 重量部
セタノール ５ 重量部
スティグマスタノールマルトシド ３ 重量部
δ−トコフェロール ０．１重量部
ロ
表４記載のポリグリセリン脂肪酸エステル ５ 重量部
ジプロピレングリコール １０ 重量部
グリセリン ５ 重量部
フェノキシエタノール １ 重量部
ハ
水 ６８．９重量部
【００２１】
【表４】
＜実施例１５＞
下記処方に従って、本発明の皮膚外用製剤１５を作成した。作成方法は皮膚外用製剤１に準じた。このものは、クリーム状で、４０℃２ヶ月保存でも安定であり、取り分け優れた安定性を有していた。
イ
小麦胚芽由来フィトステロール混合物 ２ 重量部
セタノール ５ 重量部
ウルソール酸ベンジル ３ 重量部
δ−トコフェロール ０．１重量部
ロ
デカグリセリンモノステアレート ４ 重量部
「ハイグリオール−Ｓ２６」 １ 重量部
ジプロピレングリコール １０ 重量部
グリセリン ５ 重量部
フェノキシエタノール １ 重量部
ハ
水 ６８．９重量部
【００２３】
【発明の効果】
本発明によれば、皮膚外用剤において、難溶性の素材の生体利用性を高める手段を提供することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a skin external preparation useful for enhancing the bioavailability of a hardly soluble material in a skin external preparation such as a cosmetic or a skin external medicine.
[0002]
[Prior art]
In a composition having an action on the living body as an essential component, such as a pharmaceutical or a cosmetic, among the substances responsible for the action on the living body, a water-soluble or low oil-soluble substance, that is, a poorly soluble substance Not a few materials. For example, for pharmaceuticals, dihydropyridine cardiovascular drugs such as nifedipine and nicardipine, benzylamine antifungals, imidazole antifungals, nonsteroidal anti-inflammatory drugs such as indomethacin, steroids such as betamethasone and beclomethasone Heterocyclic compounds such as anti-inflammatory agents, for cosmetics, benzophenones such as oxybenzone, heterocyclic compounds such as steroids such as ethinylestradiol, and substances having a hydrophobic mother nucleus such as phytosteside Glycosides, ursolic acid, salts of ursolic acid or triterpenes such as aromatic esters of ursolic acid and their derivatives fall under this poorly soluble material. In addition, extracts of herbal medicines containing these substances using organic solvents and exhibiting poor solubility also fall under such hardly soluble substances. Each of these materials exhibits an excellent action in a uniformly dissolved solution system, but in an ordinary emulsification system, etc., it takes a finely dispersed form of crystals or solids. There were many cases that could not be demonstrated. That is, it can be said that the effectiveness was remarkably reduced due to the physicochemical property of low solubility. For this reason, various attempts have been made to improve the bioavailability of such materials. Such attempts include, for example, a method of dispersing the material into fine particles using a nonionic surfactant having a polyoxyethylene group of 60 mol or more (Patent Document 1), a water-dispersible polymer, and the like. A method of forming a matrix and forming a polymer micelle (Patent Document 2), or a method in which a highly soluble vehicle such as triethylene glycol and C4-6 dihydric alcohol coexists and depends on the solvent effect (Patent) Document 3) is known. However, in these methods, the effect is not sufficient, and in such a system, the crystal of the raw material sometimes precipitates, and the improvement has been desired from the viewpoint of stability.
[0003]
On the other hand, as a technique for combining an aliphatic saturated alcohol having 12 to 24 carbon atoms or phytosterol with a poorly soluble material, there is a method of reducing the bitterness of the hardly soluble material by coating with such an alcohol, No attempt has been made to make a matrix by using this together with a hardly soluble material, thereby improving bioavailability. There is no known composition of a matrix containing 1 to 5 times the amount of the following alcohols with respect to the hardly soluble material, and the bioavailability of the hardly soluble material can be improved by taking such a structure. It is not known at all that it can be significantly increased.
[0004]
[Patent Document 1]
JP 2001-122767 A [Patent Document 2]
JP 2001-226294 A [Patent Document 3]
Japanese Patent Laid-Open No. 2000-327588
[Problems to be solved by the invention]
The present invention has been made under such circumstances, and an object of the present invention is to provide means for enhancing bioavailability of a hardly soluble material in a skin external preparation.
[0006]
[Means for solving problems]
In view of such a situation, the present inventors have sought for means for enhancing the bioavailability of a hardly soluble material in a skin external preparation, and as a result of earnest research efforts, the skin containing the hardly soluble material is obtained. A preparation for external use, wherein a matrix containing an alcohol such as an aliphatic saturated alcohol having 12 to 24 carbon atoms and phytosterol is dispersed in a vehicle in an amount of 1 to 5 times the amount of the hardly soluble material. It was found that the external preparation for skin had such properties, and the present invention was completed. That is, this invention relates to the technique shown below.
(1) A liquid crystal containing one or more selected from the hardly soluble materials shown below and 1 to 5 times the amount of the alcohols listed below with respect to the hardly soluble material. a matrix that partially form a distributed and external skin preparation comprising,
1 ) The matrix constituent component containing the hardly soluble material and the alcohol is heated to be compatible,
2) After that, the matrix is diluted with a non-aqueous component other than the matrix component, which contains a surfactant and a polyhydric alcohol, which has been preliminarily mixed with warming, to obtain a diluted product,
3) An external preparation for skin, which is produced by adding a pre-warmed aqueous component to the dilution and cooling.
(Sparingly soluble material)
Phytosterol glycosides, isoflavones, glycosides of isoflavones, triterpenic acids and / or their salts, aromatic esters of triterpenic acids (alcohols)
C12-24 aliphatic saturated alcohol, phytosterol (2) wherein the hardly soluble material is selected from phytosterol glycoside, ursolic acid, ursolic acid salt and ursolic acid aromatic ester The external preparation for skin according to (1), which is at least two kinds.
(3) The external preparation for skin according to (1) or (2), further comprising a fatty acid ester of polyglycerol.
(4) The external preparation for skin according to (3), wherein the fatty acid ester of polyglycerin is a mono fatty acid ester of decaglycerin.
(5) 1) Warm and dissolve the matrix constituents containing the hardly soluble material and alcohol,
2) After that, dilute with a non-aqueous component other than the matrix component, which contains a surfactant and a polyhydric alcohol, which has been preliminarily heated and dissolved, and 3) preheat the diluted product. The method for producing an external preparation for skin according to any one of (1) to (4), wherein the aqueous component is added and cooled.
Surfactants are oriented around the luma trix droplets to contain (6) poorly soluble materials and alcohols, characterized in that it is in the form dispersed in an aqueous carrier, the production method according to (5) .
(7) surfactants are oriented around the matrix droplets containing poorly soluble materials and alcohols, characterized in that it is a dispersed form in an aqueous carrier, either (1) to (4) The external preparation for skin described in 1.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
(1) Slightly soluble material that is an essential component of the external preparation for skin of the present invention The external preparation for skin of the present invention contains a hardly soluble material as an essential component. The hardly soluble material referred to in the present invention is a heterocyclic compound, a glycoside of a substance having a hydrophobic mother nucleus or a triterpene and a derivative thereof, and its basic property is hardly soluble in water, and The oil component is hardly dissolved under the condition of 1 atm and 20 ° C., and has the property of precipitating fine crystals or amorphous solids. The purpose of blending in the external preparation for skin is moisturizing action, cleansing action, preventing and improving rough skin, whitening action, UV protection action, and anti-inflammatory action. As specific compounds, in pharmaceuticals, dihydropyridine cardiovascular drugs such as nifedipine and nicardipine as heterocyclic compounds, benzylamine antifungals, imidazole antifungals, nonsteroidal anti-inflammatory drugs such as indomethacin In cosmetics, such as steroidal anti-inflammatory drugs such as betamethasone and beclomethasone, glycosides of substances having a hydrophobic mother nucleus such as benzophenones such as oxybenzone as heterocyclic compounds and steroids such as ethinylestradiol Examples thereof include phytosteside as a body, ursolic acid, a salt of ursolic acid or an aromatic ester of ursolic acid as a derivative of triterpene. In addition, extracts of herbal medicines containing these substances using organic solvents and exhibiting poor solubility also fall under such hardly soluble substances. Preferable specific examples of the hardly soluble substance include glycosides of phytosterols such as campesterol glucoside, sitosterol glucoside, stigmasteranol glucoside, stigmasteranol maltoside, isoflavones such as soybean enine, glycosides of isoflavones such as soybean in, oleanolic acid, Asian acids, triterpenic acids such as ursolic acid, alkali metal salts such as sodium salts and potassium salts thereof, alkaline earth metal salts such as calcium and magnesium, organic amine salts such as ammonium salts, triethanolamine salts, triethylamine salts, Preferred examples include basic amino acid salts such as lysine salts and arginine salts, and aromatic esters of triterpenic acid such as benzyl esters and phenethyl esters. Among them, phytosterol glycosides, urso Le acids, aromatic ester salts of ursolic acid and ursolic acid can be exemplified. Such components contain one or more appropriately selected amounts in an amount suitable for the pharmacological action. Specifically, the total amount is preferably 0.1 to 10% by weight, more preferably 0.2 to 5% by weight, based on the total amount of the external preparation for skin.
[0008]
(2) Alcohols as essential components of the preparation for external use of the present invention The external preparation for skin of the present invention contains alcohols as essential components. Preferable examples of the alcohols include aliphatic saturated alcohols having 12 to 24 carbon atoms such as lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, and isostearyl alcohol, and phytosterols such as campesterol, stigmasteranol, and sitosterol. it can. Such alcohols form a composite matrix in which liquid crystals, solid solutions, solution states, and the like are mixed together with the hardly soluble material, and exert an effect of enhancing the bioavailability of the hardly soluble material. In order to exert such an action, the alcohol is preferably contained in a total amount of 1 to 5 times the total amount of the hardly soluble material. Therefore, 0.1-50 weight% is preferable with respect to the skin external preparation whole quantity, and 0.2-25 weight% is still more preferable.
[0009]
(3) Fatty acid ester of polyglycerol which is a preferred component of the external preparation for skin of the present invention The external preparation for skin of the present invention is characterized by containing a fatty acid ester of polyglycerin as a preferred component. As the fatty acid ester of polyglycerin, those having a hydrophilic / lipophilic balance (HLB) of 10 or more are preferable. The polyglycerol group of the polyglycerol fatty acid ester preferably has a degree of polymerization of 5 or more, particularly preferably 8 to 12. The fatty acid residues include those having 12 to 24 carbon atoms such as lauric acid residues, myristic acid residues, palmitic acid residues, stearic acid residues, behenic acid residues, isostearic acid residues and oleic acid residues. Those are particularly preferred. The number of the fatty acid residues is preferably larger than the number of free hydroxyl groups, and preferably 5 to 20 times the number of fatty acid residues is present. Specifically preferred are decaglycerin monostearate (HLB13.5), pentaglycerin monostearate (HLB11), decaglycerin isostearate (HLB13.5), pentaglycerin monostearate (HLB11). ), Decaglycerin monooleate (HLB13) and the like. Such a component acts as a hydrophilic surfactant in the external preparation for skin of the present invention. Polyglycerin fatty acid esters easily form a liquid crystal structure together with poorly water-soluble components and alcohols, and when such a liquid crystal structure is formed in at least a part of the matrix, the hardly soluble component is easily absorbed through the skin, Becomes present on the skin. As a treatment method that easily generates liquid crystal, 1) a matrix component containing a hardly soluble material and an alcohol is heated to be compatible, and 2) after that, a surfactant that has been heated and compatible in advance. It is diluted with a non-aqueous component other than a matrix component, which contains a polyglycerin fatty acid ester and a polyhydric alcohol, and 3) a pre-warmed aqueous component is added to the dilution and cooled. Can be preferably exemplified. Such a component can contain only one species or a combination of two or more species. The preferable content of such components in the external preparation for skin of the present invention is 0.1 to 10% by weight, more preferably 1 to 5 parts by weight, based on the total amount of the external preparation for skin. Moreover, it is preferable that the quantity of the fatty-acid ester of polyglycerol is 70 to 300 weight% with respect to the total amount of a hardly soluble component.
[0010]
(4) External preparation for skin of the present invention The external preparation for skin of the present invention contains 1) a poorly soluble material, 2) an alcohol, a fatty acid ester of polyglycerol as a preferred component, and the hardly soluble salt. The liquid crystal, the solution (dissolved part) and the matrix in which the crystals are mixed are dispersed. Using these components, to produce a formulation comprising a liquid crystal structure, for example, it is carried out the following process can be preferably exemplified. 1) Warmly compatibilizing matrix constituents containing a hardly soluble material and alcohols, and 2) After that, the fatty acid ester of polyglycerin, which is a surfactant, and polyhydric acid, which were preliminarily heated and compatible. Dilute with a non-aqueous component other than the matrix component containing alcohol, and 3) add a pre-warmed aqueous component to the dilution and cool . Examples of non-aqueous components other than the hardly soluble material constituting the dilution include 1,3-butanediol, diprene glycol, glycerin , diglycerin, isoprene glycol, 1,2-pentanediol, 1,2- Examples include polyhydric alcohols such as hexylene glycol, antibacterial components such as phenoxyethanol, and surfactants other than fatty acid esters of polyglycerol. As the surfactant other than the fatty acid ester of polyglycerin, a nonionic surfactant can be preferably exemplified, and among these, a surfactant having no polyoxyethylene skeleton can be particularly preferably exemplified. Preferred examples of such surfactants include sucrose fatty acid esters and polyglyceryl polyoxybutylene alkyl (alkenyl) ethers. There are many commercially available sucrose fatty acid esters that can be used. Polyglyceryl polyoxybutylene alkyl (alkenyl) ether can be produced, for example, by the method described in JP-A-59-1403. That is, a higher alcohol, glycidol and tetrahydrofuran can be obtained by reacting with a Lewis acid or alkali as a catalyst. The preferable addition mole number of the glyceryl group in polyglyceryl polyoxybutylene alkyl (alkenyl) ether is 5-25, More preferably, it is 10-20. The preferred added mole number of the oxybutylene group is 5 to 25, and more preferably 10 to 20. Moreover, as an alkyl (alkenyl) group, a C10-C30 thing is preferable, For example, a lauryl group, a cetyl group, a stearyl group, an oleyl group, an isostearyl group, a dodecyldecyl group etc. can be illustrated suitably. Such polyglyceryl polyoxybutylene alkyl (alkenyl) ethers can be produced and used as described above, but some are already commercially available, and such commercially available products can also be used. Preferable examples of commercially available products include “High Glyol-S26” (polyglyceryl (13) polyoxybutylene (14) stearyl ether) commercially available from Nikko Chemicals Corporation. The preferable content of the sucrose fatty acid ester and polyglyceryl polyoxybutylene alkyl (alkenyl) ether is 0.05 to 10% by weight and 0.1 to 5% by weight based on the total amount of the external preparation for skin. Further preferred.
[0011]
In the external preparation for skin of the present invention, an optional ingredient usually used in an external preparation for skin such as cosmetics or external medicine for skin is used as a phase of liquid crystal forming component, liquid crystal forming, within the range not impairing the effect of the present invention. It can be contained separately in any phase of a non-aqueous component other than the component and a water phase. Such optional components include, for example, hydrocarbons such as squalane, liquid paraffin, light liquid isoparaffin, heavy liquid isoparaffin, microcrystalline wax, solid paraffin, dimethicone, femethicone, cyclomethicone, amodimethicone, polyether-modified silicone, etc. Silicones, jojoba oil, carnauba wax, owl, beeswax, geiwa, octyldodecyl oleate, isopropyl myristate, esters such as neopentyl glycol diisostearate, diisostearate malate, stearic acid, lauric acid, Fatty acids such as myristic acid, palmitic acid, isostearic acid, isopalmitic acid, behenic acid, oleic acid, castor oil, coconut oil, hydrogenated coconut oil, coconut oil, wheat germ oil, isostearic acid Triglycerides such as glyceride, isooctanoic acid triglyceride, olive oil, 1,3-butanediol, glycerin, diglycerin, dipropylene glycol, polyethylene glycol, 1,2-pentanediol, 1,2-hexylene glycol, isoprene glycol, etc. Polyhydric alcohol, crystalline cellulose, cross-linked methylpolysiloxane, organic powders such as polyethylene powder and acrylic resin powder, talc, mica, sericite, magnesium carbonate, calcium carbonate, titanium dioxide, iron oxide, bitumen, ultramarine , Titanium mica, titanium sericite, silica-treated powders, acrylic acid / alkyl methacrylate copolymer and / or salt thereof, carboxyvinyl polymer and / or salt thereof, xanthan gum and Thickeners such as roxypropyl cellulose, active ingredients such as vitamins such as retinol, retinoic acid, tocopherol, riboflavin, pyridoxine, ascorbic acid, ascorbic acid phosphate, and steroids such as estradiol, ethinylestradiol, estriol, phenoxyethanol Preferable examples include preservatives such as parabens, hibiten gluconate and benzalkonium chloride, and ultraviolet absorbers such as dimethylaminobenzoic acid esters, cinnamic acid esters and benzophenones. The external preparation for skin of the present invention can be applied as a preparation for cosmetics or a pharmaceutical preparation for external use for skin, but it is particularly preferable to apply it to cosmetics.
[0012]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples, but it is needless to say that the present invention is not limited to such examples.
[0013]
<Example 1>
According to the formulation shown below, the external preparation for skin of the present invention containing stigmasteranol maltoside (a glycoside of plant sterol) as a hardly soluble material was prepared. That is, it was confirmed that the temperatures of A, B, and C were each adjusted to 95 ° C. and became uniform. The mixture was diluted with b, and further diluted with stirring, and stirred and cooled to obtain an emulsion 1 for external application to the skin of the present invention. When this was observed under a polarizing microscope, as shown in FIG. 3 (photograph substituted for a drawing), small particles in which a portion having a liquid crystal structure and a portion not having the same are mixed are uniformly dispersed. I understood it. In addition, the liquid crystal is partially formed in (i) that is in a uniform state, and the liquid that is diluted by adding (b) is a multiphase state in which the liquid state and the liquid crystal and the vehicle coexist. I also understood that. As Comparative Example 1, an emulsion was prepared using the same formulation ingredients and changing the order of addition. Even when this was observed under a polarizing microscope, no fluorescence was observed, indicating that no liquid crystal structure was present. Their stability (storage condition at 40 ° C. for 1 month) was also examined. As a result, it was confirmed that the preparation 1 for external use for skin was stably present, but separation was observed in Comparative Example 1, and the stability was improved by constituting a matrix in which the liquid crystal structure was partially present. It was done.
1 Wheat germ derived phytosterol mixture 2 parts by weight cetanol 5 parts by weight stigmasteranol maltoside 3 parts by weight δ-tocopherol 0.1 part by weight rodecaglycerin monostearate 5 parts by weight dipropylene glycol 10 parts by weight glycerin 5 parts by weight phenoxyethanol 1 part by weight 68.9 parts by weight of water (Comparative Example 1)
A wheat germ-derived phytosterol mixture 2 parts by weight cetanol 5 parts by weight stigmasteranol maltoside 3 parts by weight δ-tocopherol 0.1 parts by weight decaglycerin monostearate 5 parts by weight phenoxyethanol 1 part by weight dipropylene glycol 10 parts by weight glycerin 5 parts by weight Water 68.9 parts by weight Production method) A and B were each adjusted to a temperature of 95 ° C., and gradually added to a with stirring and cooled with stirring to obtain an emulsion.
[0014]
<Example 2>
Using the skin external preparation 1 of Example and Comparative Example 1, the feeling of use by a specialized panel was compared. The feeling of use is good spread, moist feeling after application, smoothness of the skin after application, score 5: very good, score 4: good, score 3: slightly good, score 2: slightly bad, score 1 : Evaluation was performed based on bad standards. The results are shown in Table 1. This shows that the external preparation for skin of the present invention has an excellent feeling of use. Further, it is understood that the good feeling of use is that stigmasteranol maltoside is dispersed in a matrix state in which a partial liquid crystal exists.
[0015]
[Table 1]
<Example 3>
With respect to the external preparation for skin 1 and Comparative Example 1, the anti-stigging action was examined. That is, using a paneler that feels stinging at a threshold value of 0.01% with respect to methylparaben (the minimum concentration at which irritation is felt when contacted with a methylparaben solution is 0.01%), the inner side of the lower arm is 4 cm × 4 cm. After the site was prepared and 30 μl of sample was applied and treated, a cotton swab was impregnated with 10% in1,3-butanediol aqueous solution of various concentrations and contacted to examine the threshold value for feeling stinging. The results are shown in Table 2. From this, it can be seen that the external preparation 1 for skin has an effect of suppressing staggering 20 times or more compared with Comparative Example 1. (○ in the table indicates no stinging, × indicates stinging, and Δ indicates whether stinging is present or not)
[0017]
[Table 2]
<Examples 4 to 10>
Whether or not a liquid crystal dispersion system can be formed by changing the poorly soluble material of the external preparation for skin 1 was examined. The results are shown in Table 3. From this, it was found that any poorly soluble material produces a matrix dispersion in which liquid crystals partially exist. In addition, the manufacturing method followed the skin external preparation 1.
(I) Wheat germ-derived phytosterol mixture 2 parts by weight cetanol 5 parts by weight Insoluble component shown in Table 3 3 parts by weight δ-tocopherol 0.1 part by weight rodaglycerin monostearate 5 parts by weight dipropylene glycol 10 parts by weight glycerin 5 parts by weight Parts Phenoxyethanol 1 part by weight C water 68.9 parts by weight
[Table 3]
<Examples 11 to 14>
The decaglycerin monostearate of the external preparation 1 for skin was changed to another polyglycerin fatty acid ester to examine whether or not a liquid crystal dispersion system was possible. The results are shown in Table 4. From this, it turns out that all the polyglyceryl fatty acid ester of HLB10 or more can be used in the external preparation for skin of this invention.
A wheat germ-derived phytosterol mixture 2 parts by weight cetanol 5 parts by weight Stigmasteranol maltoside 3 parts by weight δ-tocopherol 0.1 parts by weight b Polyglycerin fatty acid ester described in Table 4 5 parts by weight dipropylene glycol 10 parts by weight glycerin 5 parts by weight Phenoxyethanol 1 part by weight C Water 68.9 parts by weight
[Table 4]
<Example 15>
A skin external preparation 15 of the present invention was prepared according to the following formulation. The preparation method was in accordance with Formulation 1 for external application to the skin. This product was creamy and stable even when stored at 40 ° C. for 2 months, and in particular, had excellent stability.
1 Wheat germ-derived phytosterol mixture 2 parts by weight cetanol 5 parts by weight benzylursolate 3 parts by weight δ-tocopherol 0.1 part by weight Rhodecaglycerin monostearate 4 parts by weight “High Glyol-S26” 1 part by weight dipropylene glycol 10 parts by weight Parts glycerin 5 parts by weight phenoxyethanol 1 part by weight water 68.9 parts by weight
【The invention's effect】
ADVANTAGE OF THE INVENTION According to this invention, the means for improving the bioavailability of a hardly soluble raw material can be provided in a skin external preparation.
Claims (7)
１）前記難溶性の素材と前記アルコール類を含有するマトリックス構成成分を加温して相溶させ、
２）しかる後に、予め加温相溶させておいた、界面活性剤と多価アルコールを含有する、マトリックス構成成分以外の非水成分で、前記マトリックスを希釈し、希釈物とし、
３）該希釈物に、予め加温しておいた水性成分を加え、冷却することにより、製造されることを特徴とする、皮膚外用製剤。
（難溶性の素材）
フィトステロールの配糖体、イソフラボン、イソフラボンの配糖体、トリテルペン酸および／又はそれらの塩、トリテルペン酸の芳香族エステル
（アルコール類）
炭素数１２〜２４の脂肪族飽和アルコール、フィトステロール 1 part or 2 or more types selected from the hardly soluble material shown below, and 1 to 5 times the amount of alcohol mentioned below with respect to the said hardly soluble material , The liquid crystal partially the matrix forming a distributed and external skin preparation comprising,
1) The matrix constituent component containing the hardly soluble material and the alcohol is heated to be compatible,
2) After that, the matrix is diluted with a non-aqueous component other than the matrix component, which contains a surfactant and a polyhydric alcohol, which has been preliminarily mixed with warming, to obtain a diluted product,
3) An external preparation for skin, which is produced by adding a pre-warmed aqueous component to the dilution and cooling.
(Sparingly soluble material)
Phytosterol glycosides, isoflavones, glycosides of isoflavones, triterpenic acids and / or their salts, aromatic esters of triterpenic acids (alcohols)
C12-24 aliphatic saturated alcohol, phytosterol
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003130921A JP4430889B2 (en) | 2003-05-09 | 2003-05-09 | Preparations for topical skin containing sparingly soluble materials |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003130921A JP4430889B2 (en) | 2003-05-09 | 2003-05-09 | Preparations for topical skin containing sparingly soluble materials |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004331593A JP2004331593A (en) | 2004-11-25 |
| JP2004331593A5 JP2004331593A5 (en) | 2006-03-16 |
| JP4430889B2 true JP4430889B2 (en) | 2010-03-10 |
Family
ID=33506232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003130921A Expired - Lifetime JP4430889B2 (en) | 2003-05-09 | 2003-05-09 | Preparations for topical skin containing sparingly soluble materials |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4430889B2 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2407748C2 (en) | 2005-06-10 | 2010-12-27 | Пола Кемикал Индастриз Инк. | New derivative of triterpenic acid and topical skin preparation containing it |
| JP4980634B2 (en) * | 2006-03-17 | 2012-07-18 | ポーラ化成工業株式会社 | Skin external preparation suitable for prevention and improvement of rough skin |
| CA2655788C (en) | 2006-06-19 | 2014-03-18 | Kuraray Co., Ltd. | Skin external preparation containing triterpenic acid |
| JP2011006347A (en) * | 2009-06-25 | 2011-01-13 | Univ Of Tsukuba | Fat cell differentiation inhibitor and use thereof |
| JP6180817B2 (en) * | 2013-06-24 | 2017-08-16 | ポーラ化成工業株式会社 | Topical skin preparation |
| JP6180816B2 (en) * | 2013-06-24 | 2017-08-16 | ポーラ化成工業株式会社 | Topical skin preparation |
| JP6713255B2 (en) * | 2015-06-23 | 2020-06-24 | ポーラ化成工業株式会社 | LCD cosmetics |
-
2003
- 2003-05-09 JP JP2003130921A patent/JP4430889B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004331593A (en) | 2004-11-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW508246B (en) | Stabilization of an unstable retinoid in oil-in-water emulsions for skin care compositions | |
| JP4527530B2 (en) | Vesicle dispersion and cosmetics containing the same | |
| CA1339029C (en) | Transparent composition | |
| EP1633313B1 (en) | Lipid composition and skin care formulation containing the same | |
| HUT73664A (en) | Pharmaceutically acceptable improved compositions containing an alcohol and a hydrophobic drug | |
| JPH06183949A (en) | Composition for treatment of acne containing salicylic acid dedivative | |
| JPS63150221A (en) | Emulsified composition containing crystalline drug | |
| JP4049216B2 (en) | Formulation with liquid crystal structure | |
| JP2003212716A (en) | Liquid crystalline emulsion composition | |
| JP5069965B2 (en) | Topical skin preparation | |
| JP4518367B2 (en) | Pore reducing agent | |
| JP4430889B2 (en) | Preparations for topical skin containing sparingly soluble materials | |
| JP2009263346A (en) | Emulsion-type cosmetic containing kinetin | |
| EP1660029A2 (en) | Compositions containing topical active agents and pentylene glycol | |
| JP2001163766A (en) | Composition containing pentacyclic triterpenic acid, particularly cosmetic composition | |
| JP2004210669A (en) | Ubiquinone-containing composition, and emulsion composition using the ubiquinone-containing composition | |
| JP2004307414A (en) | W/o/w emulsion skin care preparation for external use and method for producing the same | |
| JP2009046421A (en) | Skin care preparation for external use | |
| JP3444329B2 (en) | Water-in-oil emulsion composition | |
| JP2003267830A (en) | Liquid cosmetic | |
| JP4001310B2 (en) | Lipid complex and composition for external use containing the same | |
| JPH10316523A (en) | Oil-in-water type emilsified composition | |
| CN118831050B (en) | A 5α-reductase inhibitor alcohol-containing emulsion and its preparation method and application | |
| JP2005179320A (en) | Oil-in-water emulsified composition | |
| JP2000256125A (en) | Composition having discrete cubic structure, and its use as emulsified composition or dermatological composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060131 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060131 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20060131 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20090827 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090901 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091030 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20091215 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20091218 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20151225 Year of fee payment: 6 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4430889 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |