JP6553341B2 - Composition for external use - Google Patents
Composition for external use Download PDFInfo
- Publication number
- JP6553341B2 JP6553341B2 JP2014201438A JP2014201438A JP6553341B2 JP 6553341 B2 JP6553341 B2 JP 6553341B2 JP 2014201438 A JP2014201438 A JP 2014201438A JP 2014201438 A JP2014201438 A JP 2014201438A JP 6553341 B2 JP6553341 B2 JP 6553341B2
- Authority
- JP
- Japan
- Prior art keywords
- hyaluronic acid
- salt
- component
- weight
- feeling
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000000203 mixture Substances 0.000 title claims description 84
- 229920002674 hyaluronan Polymers 0.000 claims description 179
- 229960003160 hyaluronic acid Drugs 0.000 claims description 179
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 134
- -1 unsaturated hyaluronic acid oligosaccharide Chemical class 0.000 claims description 104
- 150000003839 salts Chemical class 0.000 claims description 101
- 229920001542 oligosaccharide Polymers 0.000 claims description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 239000002537 cosmetic Substances 0.000 claims description 13
- 238000004090 dissolution Methods 0.000 claims description 12
- 230000003020 moisturizing effect Effects 0.000 description 29
- 238000000034 method Methods 0.000 description 27
- 239000011248 coating agent Substances 0.000 description 26
- 238000000576 coating method Methods 0.000 description 26
- 239000000194 fatty acid Substances 0.000 description 24
- 235000014113 dietary fatty acids Nutrition 0.000 description 23
- 229930195729 fatty acid Natural products 0.000 description 23
- 229910052799 carbon Inorganic materials 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000009472 formulation Methods 0.000 description 11
- 239000006210 lotion Substances 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 239000004359 castor oil Substances 0.000 description 10
- 150000004665 fatty acids Chemical class 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 238000011978 dissolution method Methods 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
- 235000019438 castor oil Nutrition 0.000 description 8
- 238000011156 evaluation Methods 0.000 description 8
- 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 8
- 239000004166 Lanolin Substances 0.000 description 7
- 235000019388 lanolin Nutrition 0.000 description 7
- 229940039717 lanolin Drugs 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 235000015424 sodium Nutrition 0.000 description 7
- 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 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- 230000001629 suppression Effects 0.000 description 6
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 5
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 5
- 229920001214 Polysorbate 60 Polymers 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000000470 constituent Substances 0.000 description 5
- 150000002016 disaccharides Chemical class 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 229940097043 glucuronic acid Drugs 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 150000002772 monosaccharides Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 239000002280 amphoteric surfactant Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108010003272 Hyaluronate lyase Proteins 0.000 description 3
- 102000009066 Hyaluronoglucosaminidase Human genes 0.000 description 3
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 3
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 3
- 229920002385 Sodium hyaluronate Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- 239000003240 coconut oil Substances 0.000 description 3
- 235000019864 coconut oil Nutrition 0.000 description 3
- 239000013065 commercial product Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 238000005227 gel permeation chromatography Methods 0.000 description 3
- 229960002773 hyaluronidase Drugs 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 159000000003 magnesium salts Chemical class 0.000 description 3
- 238000009629 microbiological culture Methods 0.000 description 3
- 229950006780 n-acetylglucosamine Drugs 0.000 description 3
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 229940010747 sodium hyaluronate Drugs 0.000 description 3
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000001593 sorbitan monooleate Substances 0.000 description 3
- 229940035049 sorbitan monooleate Drugs 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical class CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ULQISTXYYBZJSJ-UHFFFAOYSA-N 12-hydroxyoctadecanoic acid Chemical compound CCCCCCC(O)CCCCCCCCCCC(O)=O ULQISTXYYBZJSJ-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004373 Pullulan Substances 0.000 description 2
- 229920001218 Pullulan Polymers 0.000 description 2
- 241001524200 Sinomonas atrocyanea Species 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 229960003237 betaine Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000003093 cationic surfactant Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Natural products C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- YRIUSKIDOIARQF-UHFFFAOYSA-N dodecyl benzenesulfonate Chemical compound CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 YRIUSKIDOIARQF-UHFFFAOYSA-N 0.000 description 2
- 229940071161 dodecylbenzenesulfonate Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
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- 235000019271 petrolatum Nutrition 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 235000019423 pullulan Nutrition 0.000 description 2
- 150000003214 pyranose derivatives Chemical group 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000001587 sorbitan monostearate Substances 0.000 description 2
- 229940035048 sorbitan monostearate Drugs 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
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 150000004044 tetrasaccharides Chemical class 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- WFXHUBZUIFLWCV-UHFFFAOYSA-N (2,2-dimethyl-3-octanoyloxypropyl) octanoate Chemical compound CCCCCCCC(=O)OCC(C)(C)COC(=O)CCCCCCC WFXHUBZUIFLWCV-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
- IRTMUORPUKFXOQ-UQKRIMTDSA-N (2s)-2-(dodecanoylamino)pentanedioic acid;sodium Chemical compound [Na].CCCCCCCCCCCC(=O)N[C@H](C(O)=O)CCC(O)=O IRTMUORPUKFXOQ-UQKRIMTDSA-N 0.000 description 1
- ZYJZBFYRVKLOAA-KRWDZBQOSA-N (2s)-2-(hexadecanoylamino)butanedioic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@H](C(O)=O)CC(O)=O ZYJZBFYRVKLOAA-KRWDZBQOSA-N 0.000 description 1
- QLSANCGSHSPSDS-FJSYBICCSA-N (2s)-2-(octadecanoylamino)pentanedioic acid;sodium Chemical compound [Na].[Na].CCCCCCCCCCCCCCCCCC(=O)N[C@H](C(O)=O)CCC(O)=O QLSANCGSHSPSDS-FJSYBICCSA-N 0.000 description 1
- MTJZWYHTZFVEGI-INIZCTEOSA-N (2s)-2-(tetradecanoylamino)pentanedioic acid Chemical compound CCCCCCCCCCCCCC(=O)N[C@H](C(O)=O)CCC(O)=O MTJZWYHTZFVEGI-INIZCTEOSA-N 0.000 description 1
- VQQFQUXKIKUEIU-DFWYDOINSA-N (2s)-5-oxopyrrolidine-2-carboxylic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.OC(=O)[C@@H]1CCC(=O)N1 VQQFQUXKIKUEIU-DFWYDOINSA-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
- FCAXDVKLWVSHGT-KVVVOXFISA-N (z)-docos-13-enoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O FCAXDVKLWVSHGT-KVVVOXFISA-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
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- 229940114072 12-hydroxystearic acid Drugs 0.000 description 1
- MXVBVDSNBADJOC-UHFFFAOYSA-N 2-(4,5-dihydroimidazol-1-yl)-4-hydroxybutanoic acid;sodium Chemical compound [Na].OCCC(C(O)=O)N1CCN=C1 MXVBVDSNBADJOC-UHFFFAOYSA-N 0.000 description 1
- XPALGXXLALUMLE-UHFFFAOYSA-N 2-(dimethylamino)tetradecanoic acid Chemical compound CCCCCCCCCCCCC(N(C)C)C(O)=O XPALGXXLALUMLE-UHFFFAOYSA-N 0.000 description 1
- LNCJHVLXANMHHD-UHFFFAOYSA-N 2-[2-heptadecyl-1-(2-hydroxyethyl)-4,5-dihydroimidazol-1-ium-1-yl]acetate Chemical compound CCCCCCCCCCCCCCCCCC1=NCC[N+]1(CCO)CC([O-])=O LNCJHVLXANMHHD-UHFFFAOYSA-N 0.000 description 1
- WBIQQQGBSDOWNP-UHFFFAOYSA-N 2-dodecylbenzenesulfonic acid Chemical compound CCCCCCCCCCCCC1=CC=CC=C1S(O)(=O)=O WBIQQQGBSDOWNP-UHFFFAOYSA-N 0.000 description 1
- JGUMTYWKIBJSTN-UHFFFAOYSA-N 2-ethylhexyl 4-[[4,6-bis[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 JGUMTYWKIBJSTN-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-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
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000186063 Arthrobacter Species 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- WCVRQHFDJLLWFE-UHFFFAOYSA-N pentane-1,2-diol Chemical compound CCCC(O)CO WCVRQHFDJLLWFE-UHFFFAOYSA-N 0.000 description 1
- BPHQIXJDBIHMLT-UHFFFAOYSA-N perfluorodecane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F BPHQIXJDBIHMLT-UHFFFAOYSA-N 0.000 description 1
- YVBBRRALBYAZBM-UHFFFAOYSA-N perfluorooctane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F YVBBRRALBYAZBM-UHFFFAOYSA-N 0.000 description 1
- 239000010702 perfluoropolyether Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920001083 polybutene Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- ONQDVAFWWYYXHM-UHFFFAOYSA-M potassium lauryl sulfate Chemical compound [K+].CCCCCCCCCCCCOS([O-])(=O)=O ONQDVAFWWYYXHM-UHFFFAOYSA-M 0.000 description 1
- 229940116985 potassium lauryl sulfate Drugs 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 108700004121 sarkosyl Proteins 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- 229940082004 sodium laurate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940045870 sodium palmitate Drugs 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- GGXKEBACDBNFAF-UHFFFAOYSA-M sodium;hexadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCC([O-])=O GGXKEBACDBNFAF-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 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
- 235000011076 sorbitan monostearate Nutrition 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
- 239000007921 spray Substances 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- SVETUDAIEHYIKZ-IUPFWZBJSA-N tris[(z)-octadec-9-enyl] phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCCOP(=O)(OCCCCCCCC\C=C/CCCCCCCC)OCCCCCCCC\C=C/CCCCCCCC SVETUDAIEHYIKZ-IUPFWZBJSA-N 0.000 description 1
- 229940124543 ultraviolet light absorber Drugs 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- 239000004711 α-olefin Substances 0.000 description 1
Classifications
-
- 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
- A61K8/60—Sugars; Derivatives 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
-
- 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
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)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、高濃度のヒアルロン酸を含有する外用組成物に関する。より具体的には、本発明は、高濃度のヒアルロン酸を含んでいながら、ヒアルロン酸が本来備える重厚な塗布感及び保湿感を損なうことなく、べたつきを抑え、塗布時に伸ばし易く、優れた使用感が得られる外用組成物に関する。 The present invention relates to an external use composition containing a high concentration of hyaluronic acid. More specifically, the present invention, while containing a high concentration of hyaluronic acid, suppresses stickiness and easily spreads at the time of application without impairing the heavy coating feeling and moisturizing feeling inherent to hyaluronic acid, and the excellent use The present invention relates to an external composition that can provide a feeling.
ヒアルロン酸及びその塩は、皮膚に保湿感や重厚な塗布感を付与できるため、化粧料等の外用組成物の分野で広く使用されている。また、近年、外用組成物の機能性の向上に対する要求は益々高まっており、ヒアルロン酸及びその塩を高濃度で含有させることにより、ヒアルロン酸による保湿感や重厚な塗布感をより一層効果的に付与できる外用組成物が要望されている。 Hyaluronic acid and salts thereof can be widely used in the field of compositions for external use such as cosmetics because they can impart moisturizing feeling and heavy application feeling to the skin. Moreover, in recent years, the demand for functional improvement of the composition for external use is increasing more and more, by containing hyaluronic acid and its salt at a high concentration, the moisturizing feeling and heavy coating feeling by hyaluronic acid are made more effective. There is a need for external compositions that can be applied.
一方、ヒアルロン酸及びその塩には、べたつきが生じる、塗布時の伸ばし易さが低下する等の欠点がある。特に、このような欠点は、外用組成物に高濃度のヒアルロン酸を配合した場合に顕著になる。従来、このようなヒアルロン酸及びその塩の欠点を解消する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、ヒアルロン酸と共に、ガム質、特定の四級アンモニウム塩を配合することによって、べたつきを抑制して使用感を向上できることが報告されている。また、特許文献2には、ヒアルロン酸と、1,2−ペンタンジオール、ポリグリセリン、及び/又はポリオキシプロピレンジグリセリルエーテルとを併用することによっても、べたつきを抑制して使用感を向上できることが報告されている。 On the other hand, hyaluronic acid and its salts have disadvantages such as stickiness and ease of spreading upon application. In particular, such a drawback becomes prominent when a high concentration of hyaluronic acid is added to the external composition. Heretofore, various studies have been made on formulations for solving the disadvantages of such hyaluronic acid and its salts. For example, Patent Document 1 reports that, by blending a gum and a specific quaternary ammonium salt with hyaluronic acid, it is possible to suppress stickiness and improve the feeling of use. Further, in Patent Document 2, it is also possible to suppress stickiness and improve the feeling of use by using hyaluronic acid in combination with 1,2-pentanediol, polyglycerin and / or polyoxypropylene diglyceryl ether. It has been reported.
しかしながら、特許文献1及び2の技術では、ヒアルロン酸及びその塩が本来備える重厚な塗布感及び保湿感が損なわれてしまうという欠点がある。そのため、従来の処方で高濃度のヒアルロン酸を配合しても、ヒアルロン酸及びその塩が本来備える重厚な塗布感及び保湿感を損なうことなく、べたつき抑制、塗布時に伸ばし易さの向上を図ることができず、消費者の要求を満足できる使用感を備えさせることができなかった。 However, the techniques of Patent Documents 1 and 2 have a disadvantage that the heavy coating feeling and moisturizing feeling originally provided for hyaluronic acid and its salt are impaired. Therefore, even if high concentration hyaluronic acid is blended by the conventional formulation, it is possible to suppress stickiness and improve ease of application at the time of application without impairing the heavy coating feeling and moisturizing feeling originally provided by hyaluronic acid and its salts. It was not possible to have a feeling of use that satisfied consumer demand.
また、ヒアルロン酸及びその塩は、水への溶解性が悪く、水に溶解させる際にダマ(塊状)になり易いため、高濃度のヒアルロン酸を含む外用組成物を製造する際にヒアルロン酸の溶解に長時間要し、製造コストが上昇するという問題点がある。そのため、高濃度のヒアルロン酸及び/又はその塩を含む外用組成物の開発には、ヒアルロン酸及び/又はその塩の溶解性を向上させて溶解時間を短縮させる技術の確立も求められる。 In addition, hyaluronic acid and salts thereof have poor solubility in water and tend to become lumpy (lumpy) when dissolved in water, and therefore, when preparing an external composition containing high concentration of hyaluronic acid, hyaluronic acid Dissolving takes a long time, and there is a problem that the manufacturing cost increases. Therefore, the development of a composition for external use containing a high concentration of hyaluronic acid and / or a salt thereof requires establishment of a technique for improving the solubility of hyaluronic acid and / or a salt thereof to shorten the dissolution time.
本発明の目的は、高濃度のヒアルロン酸及び/又はその塩を含む外用組成物において、ヒアルロン酸及び/又はその塩が本来備える重厚な塗布感及び保湿感を損なうことなく、べたつきを抑え、塗布時に伸ばし易くして、優れた使用感を備えさせる製剤技術を提供することである。また、本発明の他の目的は、ヒアルロン酸及び/又はその塩の溶解性を向上させ、短時間でヒアルロン酸及び/又はその塩を水に溶解させる技術を提供することである。 The object of the present invention is to reduce the stickiness and to apply the external composition containing high concentration of hyaluronic acid and / or a salt thereof without impairing the heavy coating feeling and the moisturizing feeling inherent to hyaluronic acid and / or a salt thereof. It is an object of the present invention to provide a formulation technology that makes it easy to stretch at times and provides excellent feeling of use. Another object of the present invention is to provide a technique for improving the solubility of hyaluronic acid and / or its salt and dissolving hyaluronic acid and / or its salt in water in a short time.
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、高濃度(0.05重量%以上)のヒアルロン酸及び/又はその塩を含む外用組成物に、ヒアルロン酸オリゴ糖及び/又はその塩を配合することによって、ヒアルロン酸及び/又はその塩が本来備える重厚な塗布感及び保湿感を維持しつつ、べたつきが抑制され、しかも塗布時に伸ばし易くなり、優れた使用感を備えさせ得ることを見出した。 As a result of intensive studies to solve the above-mentioned problems, the present inventor has prepared a hyaluronic acid oligosaccharide and / or a composition for external use containing hyaluronic acid and / or a salt thereof at a high concentration (0.05% by weight or more). By blending the salt, it is possible to suppress stickiness while maintaining the heavy coating feeling and moisturizing feeling inherent to hyaluronic acid and / or the salt thereof, to be easily stretched at the time of coating, and to have an excellent feeling of use I found out.
更に、本発明者は、ヒアルロン酸及び/又はその塩と共に、ヒアルロン酸オリゴ糖及び/又はその塩を水に添加することによって、ヒアルロン酸及び/又はその塩の溶解性が向上し、短時間でヒアルロン酸及び/又はその塩の水への溶解が可能になることを見出した。 Furthermore, the present inventor improves the solubility of hyaluronic acid and / or salt thereof in a short time by adding hyaluronic acid oligosaccharide and / or salt thereof together with hyaluronic acid and / or salt thereof to water. It has been found that it is possible to dissolve hyaluronic acid and / or its salt in water.
本発明は、これらの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。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)ヒアルロン酸及び/又はその塩0.05重量%以上と、(B)ヒアルロン酸オリゴ糖及び/又はその塩とを含有する、外用組成物。
項2. 前記(A)成分が、重量比で前記(B)成分の同量以上含まれる、項1に記載の外用組成物。
項3. 前記(B)成分が、0.0001〜1.5重量%含まれる、項1又は2に記載の外用組成物。
項4. 前記(B)成分が、不飽和型ヒアルロン酸オリゴ糖及び/又はその塩である、項1〜3のいずれかに記載の外用組成物。
項5. 化粧料である、項1〜4のいずれかに記載の外用組成物。
項6. (B)ヒアルロン酸オリゴ糖及び/又はその塩の存在下で、(A)ヒアルロン酸及び/又はその塩を水に溶解させることを特徴とする、ヒアルロン酸及び/又はその塩の溶解方法。
The present invention has been completed by further investigation based on these findings. That is, the present invention provides the invention of the aspects listed below.
Item 1. An external use composition comprising (A) 0.05% by weight or more of hyaluronic acid and / or a salt thereof, and (B) hyaluronic acid oligosaccharide and / or a salt thereof.
Item 2. The composition for external use according to item 1, wherein the component (A) is contained in an equal amount or more of the component (B) in a weight ratio.
Item 3. The composition for external use according to item 1 or 2, wherein the component (B) is contained in an amount of 0.0001 to 1.5% by weight.
Item 4. The composition for external use according to any one of Items 1 to 3, wherein the component (B) is unsaturated hyaluronic acid oligosaccharide and / or a salt thereof.
Item 5. The composition for external use according to any one of Items 1 to 4, which is a cosmetic.
Item 6. (B) A method for dissolving hyaluronic acid and / or a salt thereof, which comprises dissolving (A) hyaluronic acid and / or a salt thereof in water in the presence of a hyaluronic acid oligosaccharide and / or a salt thereof.
本発明によれば、高濃度(0.05重量%以上)のヒアルロン酸及び/又はその塩を含む外用組成物において、ヒアルロン酸及び/又はその塩が本来備える重厚な塗布感及び保湿感を維持しつつ、べたつきが抑制され、しかも塗布時に伸ばし易いという特性を備えさせることができる。そのため、本発明によれば、高い機能性と良好な使用感を兼ね備えた外用組成物の提供が可能になる。 According to the present invention, in a composition for external use containing hyaluronic acid and / or a salt thereof at a high concentration (0.05% by weight or more), the heavy coating feeling and moisturizing feeling inherent to hyaluronic acid and / or a salt thereof are maintained. However, stickiness can be suppressed, and it can be easily stretched during application. Therefore, according to the present invention, it is possible to provide an external composition having both high functionality and good usability.
また、本発明によれば、ヒアルロン酸及び/又はその塩の水への溶解性を向上させることができるので、高濃度のヒアルロン酸及び/又はその塩を含む外用組成物を製造する場合であっても、短時間でヒアルロン酸及び/又はその塩を水に溶解させることができ、リードタイムの短縮化や製造コストの低減が可能になる。 In addition, according to the present invention, the solubility of hyaluronic acid and / or its salt in water can be improved, so that an external composition containing a high concentration of hyaluronic acid and / or its salt is produced. Even in this case, hyaluronic acid and / or a salt thereof can be dissolved in water in a short time, and lead time can be shortened and manufacturing cost can be reduced.
1.外用組成物
本発明の外用組成物は、(A)ヒアルロン酸及び/又はその塩0.05重量%以上と、(B)ヒアルロン酸オリゴ糖及び/又はその塩とを含有することを特徴とする。以下、本発明の外用組成物について詳述する。
1. Composition for External Use The composition for external use of the present invention is characterized by containing (A) 0.05% by weight or more of hyaluronic acid and / or a salt thereof, and (B) hyaluronic acid oligosaccharide and / or a salt thereof. . Hereinafter, the external composition of the present invention will be described in detail.
(A)ヒアルロン酸及び/又はその塩
本発明の外用組成物は、重厚な塗布感及び保湿感を備えさせるために、ヒアルロン酸(所謂、高分子ヒアルロン酸)及び/又はその塩((A)成分と表記することもある)を含有する。
(A) Hyaluronic acid and / or salt thereof The composition for external use of the present invention has hyaluronic acid (so-called high molecular hyaluronic acid) and / or a salt thereof ((A) to provide a heavy coating feeling and moisturizing feeling. It may be described as an ingredient).
ヒアルロン酸は、グルクロン酸の1位の炭素原子とN−アセチルグルコサミンの3位の炭素原子がグリコシド結合により結合した2糖を繰り返し単位として含む多糖である。 Hyaluronic acid is a polysaccharide containing as a repeating unit a disaccharide in which the carbon atom at position 1 of glucuronic acid and the carbon atom at position 3 of N-acetylglucosamine are linked by a glycosidic bond.
本発明で使用されるヒアルロン酸の塩については、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、ナトリウム塩、カリウム塩等のアルカリ金属塩;カルシウム塩、マグネシウム塩などのアルカリ土類金属塩;トリ(n−ブチル)アミン塩、トリエチルアミン塩、ピリジン塩、アミノ酸塩等のアミン塩等が挙げられる。これらのヒアルロン酸の塩の中でも、好ましくはアルカリ金属塩、更に好ましくはナトリウム塩が挙げられる。これらのヒアルロン酸の塩は、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 hyaluronic acid salt used in the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, alkali metal salts such as sodium salts and potassium salts; alkaline earth salts such as calcium salts and magnesium salts; Metal salts; amine salts such as tri (n-butyl) amine salts, triethylamine salts, pyridine salts, amino acid salts, and the like. Among these salts of hyaluronic acid, preferred are alkali metal salts, more preferably sodium salts. These hyaluronic acid salts may be used alone or in combination of two or more.
本発明で使用されるヒアルロン酸及び/又はその塩の平均分子量については、特に制限されないが、例えば50万以上、好ましくは50万〜300万が挙げられる。特に、重厚な塗布感、保湿感、伸ばし易さ、及びべたつき抑制作用をより一層効果的に向上させるという観点から、ヒアルロン酸の平均分子量として、好ましくは80万〜250万、更に好ましくは100万〜250万が挙げられる。本発明において、ヒアルロン酸及び/又はその塩の平均分子量は、ゲル濾過クロマトグラフィー(GPC)法によって、プルランを標準物質として使用して求められる重量平均分子量である。 The average molecular weight of the hyaluronic acid and / or the salt thereof used in the present invention is not particularly limited, and may be, for example, 500,000 or more, preferably 500,000 to 3,000,000. In particular, the average molecular weight of hyaluronic acid is preferably 800,000 to 2,500,000, more preferably 1,000,000, from the viewpoint of more effectively improving the heavy coating feeling, moisturizing feeling, ease of stretching, and tackiness suppressing action. Up to 2.5 million. In the present invention, the average molecular weight of hyaluronic acid and / or a salt thereof is a weight average molecular weight determined by gel permeation chromatography (GPC) using pullulan as a standard substance.
本発明で使用されるヒアルロン酸及び/又はその塩の由来については、特に制限されず、鶏冠、臍帯、皮膚、関節液等の生体組織から得られた天然由来であってもよく、また、酵素反応、化学合成、微生物培養等によって生成させたものであってもよい。 The origin of the hyaluronic acid and / or salt thereof used in the present invention is not particularly limited, and may be naturally derived from a biological tissue such as chicken crown, umbilical cord, skin, joint fluid, or enzyme. It may be produced by reaction, chemical synthesis, microorganism culture or the like.
ヒアルロン酸及び/又はその塩は市販されており、本発明では、市販品を使用してもよい。ヒアルロン酸及び/又はその塩の市販品としては、具体的には、商品名「ヒアルロンサン HA−LQH」(平均分子量120〜220万;キユーピー株式会社)、商品名「ヒアルロンサン HA−LQ」(平均分子量85〜160万;キユーピー株式会社)、商品名「ヒアルロン酸FCH−200」(平均分子量180〜220万;キッコーマンバイオケミファ株式会社)、商品名「ヒアルロン酸FCH−150」(平均分子量140〜180万;キッコーマンバイオケミファ株式会社)、商品名「ヒアルロン酸FCH−120」(平均分子量100〜140万;キッコーマンバイオケミファ株式会社)、商品名「バイオヒアルロン酸ナトリウム HA9」(平均分子量80〜120万;株式会社資生堂)、商品名「バイオヒアルロン酸ナトリウム HA12」(平均分子量110〜160万;株式会社資生堂)、商品名「バイオヒアルロン酸ナトリウム HA20」(平均分子量190〜270万;株式会社資生堂)等が挙げられる。 Hyaluronic acid and / or a salt thereof are commercially available, and in the present invention, commercially available products may be used. Specifically, as a commercial product of hyaluronic acid and / or a salt thereof, the trade name "hyaluronic acid HA-LQH" (average molecular weight 120 to 220,000; Kewpie Corporation), the trade name "hyaluronic acid HA-LQ" (average molecular weight Kewpie Co., Ltd.), trade name “Hyaluronic acid FCH-200” (average molecular weight: 180 to 2.2 million; Kikkoman Biochemifa Co., Ltd.), trade name “hyaluronic acid FCH-150” (average molecular weight: 140 to 1.8 million Kikkoman Biochemifa Co., Ltd., trade name "hyaluronic acid FCH-120" (average molecular weight 100 to 1.4 million; Kikkoman Biochemifa Co., Ltd.), trade name "biohyaluronate sodium HA9" (average molecular weight 800 to 1.2 million; stock Company Shiseido), trade name "Bio hyaluronic acid Nato" Umm HA12 "(average molecular weight of 110 to 1,600,000; Shiseido Co., Ltd.), trade name" sodium bio hyaluronic acid HA20 "(average molecular weight of 190 to 2,700,000; Shiseido Co., Ltd.), and the like.
本発明の外用組成物において、(A)成分として、ヒアルロン酸又はその塩のいずれか一方を単独で使用してもよく、またこれらを組み合わせて使用してもよい。 In the composition for external use of the present invention, either one of hyaluronic acid or a salt thereof may be used alone as the component (A), or these may be used in combination.
本発明の外用組成物において、(A)成分の濃度は、0.05重量%以上に設定される。このように、(A)成分を0.05重量%以上という高濃度に設定することによって、ヒアルロン酸及び/又はその塩特有の重厚な塗布感と保湿感が効果的に発揮することが可能になる。また、従来技術では、このような高濃度で(A)成分を含有させると、べたつきが生じたり、塗布時に伸ばし難くなったりするが、本発明の外用組成物では、後述するヒアルロン酸オリゴ糖及び/又はその塩を含むことにより、べたつきが抑制され、しかも塗布時に伸ばし易くなり、使用感の向上が図られる。重厚な塗布感、保湿感、伸ばし易さ、及びべたつき抑制作用をより一層効果的に向上させるという観点から、(A)成分の濃度として、好ましくは0.05〜2重量%、更に好ましくは0.05〜1重量%が挙げられる。 In the composition for external use of the present invention, the concentration of the component (A) is set to 0.05% by weight or more. Thus, by setting the component (A) to a high concentration of 0.05% by weight or more, it is possible to effectively exert a heavy coating feeling and moisturizing feeling peculiar to hyaluronic acid and / or a salt thereof. Become. Moreover, in the prior art, when the component (A) is contained at such a high concentration, stickiness may occur or it may be difficult to stretch at the time of application. However, in the composition for external use of the present invention, hyaluronic acid oligosaccharides and By including the salt thereof, stickiness is suppressed, and it becomes easy to spread at the time of application, and the feeling in use can be improved. From the viewpoint of more effectively improving the heavy coating feeling, moisturizing feeling, ease of stretching, and stickiness-inhibiting action, the concentration of component (A) is preferably 0.05 to 2% by weight, more preferably 0. .05-1 weight% is mentioned.
(B)ヒアルロン酸オリゴ糖及び/又はその塩
本発明の外用組成物は、前記(A)成分と共に、ヒアルロン酸オリゴ糖及び/又はその塩((B)成分と表記することもある)を含有する。ヒアルロン酸オリゴ糖及び/又はその塩を使用することにより、(A)成分を0.05重量%以上という高濃度で含んでいても、(A)成分が本来備える重厚な塗布感及び保湿感を維持しつつ、べたつきを抑制し、更には塗布時に伸ばし易くなり、外用組成物に優れた使用感を備えさせることが可能になる。また、ヒアルロン酸オリゴ糖及び/又はその塩を使用することにより、(A)成分の水への溶解性を向上させ、(A)成分の溶解に要する時間を短縮することも可能になる。
(B) Hyaluronic Acid Oligosaccharide and / or its Salt The composition for external use according to the present invention contains, together with the aforementioned component (A), hyaluronic acid oligosaccharide and / or its salt (sometimes referred to as component (B)). To do. By using the hyaluronic acid oligosaccharide and / or the salt thereof, even when the component (A) is contained at a high concentration of 0.05% by weight or more, the heavy coating feeling and moisturizing feeling that the component (A) originally has While maintaining, stickiness is suppressed, and further, it becomes easy to extend at the time of application, and it becomes possible to provide the composition for external use with excellent usability. In addition, by using hyaluronic acid oligosaccharide and / or a salt thereof, it becomes possible to improve the solubility of the component (A) in water and shorten the time required to dissolve the component (A).
ヒアルロン酸オリゴ糖は、グルクロン酸の1位の炭素原子とN−アセチルグルコサミンの3位の炭素原子がグリコシド結合により結合した2糖を繰り返し単位として、当該繰り返し単位を1個以上含むオリゴ糖である。 The hyaluronic acid oligosaccharide is an oligosaccharide containing as a repeating unit a disaccharide in which a carbon atom at position 1 of glucuronic acid and a carbon atom at position 3 of N-acetylglucosamine are linked by a glycosidic bond, and the repeating unit is one or more .
本発明で使用されるヒアルロン酸オリゴ糖の塩については、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、ナトリウム塩、カリウム塩等のアルカリ金属塩;カルシウム塩、マグネシウム塩などのアルカリ土類金属塩;トリ(n−ブチル)アミン塩、トリエチルアミン塩、ピリジン塩、アミノ酸塩等のアミン塩等が挙げられる。これらのヒアルロン酸オリゴ糖の塩の中でも、好ましくはアルカリ金属塩、更に好ましくはナトリウム塩が挙げられる。これらのヒアルロン酸の塩は、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 salt of the hyaluronic acid oligosaccharide used in the present invention is not particularly limited as long as it is pharmaceutically acceptable. For example, alkali metal salts such as sodium salt and potassium salt; calcium salt and magnesium salt Examples include alkaline earth metal salts; amine salts such as tri (n-butyl) amine salts, triethylamine salts, pyridine salts, amino acid salts, and the like. Among the salts of these hyaluronic acid oligosaccharides, preferred are alkali metal salts, more preferably sodium salts. These hyaluronic acid salts may be used alone or in combination of two or more.
ヒアルロン酸オリゴ糖及び/又はその塩の構成単糖の数については、特に制限されないが、例えば、2〜16糖程度が挙げられる。重厚な塗布感、保湿感、伸ばし易さ、及びべたつき抑制をより一層効果的に向上させるという観点から、ヒアルロン酸オリゴ糖及び/又はその塩の構成単糖の数として、好ましくは2〜12糖、更に好ましくは2〜10糖、特に好ましくは2〜8糖が挙げられる。 The number of constituent monosaccharides of hyaluronic acid oligosaccharide and / or a salt thereof is not particularly limited, and examples thereof include about 2 to 16 saccharides. The number of constituent monosaccharides of hyaluronic acid oligosaccharide and / or a salt thereof is preferably 2 to 12 from the viewpoint of more effectively improving heavy coating feeling, moisturizing feeling, ease of stretching, and suppression of stickiness. And more preferably 2 to 10 sugars, particularly preferably 2 to 8 sugars.
本発明で使用されるヒアルロン酸オリゴ糖及び/又はその塩は、飽和型又は不飽和型いずれか一方を単独で使用してもよく、飽和型及び不飽和型を組み合わせて使用してもよい。重厚な塗布感、保湿感、伸ばし易さ、及びべたつき抑制をより一層効果的に向上させるという観点から、好ましくは不飽和型ヒアルロン酸オリゴ糖及び/又はその塩が挙げられる。本発明において、飽和型のヒアルロン酸オリゴ糖及び/又はその塩とは、全ての構成単糖におけるピラノース骨格が単結合で形成されているヒアルロン酸オリゴ糖及び/又はその塩である。不飽和型のヒアルロン酸オリゴ糖及び/又はその塩とは、少なくとも1つの構成単糖におけるピラノース骨格に二重結合が含まれているヒアルロン酸オリゴ糖及び/又はその塩である。不飽和型のヒアルロン酸オリゴ糖及び/又はその塩として、具体的には、非還元末端に位置するグルクロン酸の4位の炭素原子に結合している水酸基が除去され、4位の炭素原子と5位の炭素原子が二重結合で結合しているヒアルロン酸オリゴ糖及び/又はその塩が挙げられる。 As the hyaluronic acid oligosaccharide and / or salt thereof used in the present invention, either a saturated type or an unsaturated type may be used alone, or a saturated type and an unsaturated type may be used in combination. From the viewpoint of more effectively improving the heavy coating feeling, moisturizing feeling, easiness of stretching, and stickiness suppression, unsaturated hyaluronic acid oligosaccharides and / or salts thereof are preferable. In the present invention, the saturated hyaluronic acid oligosaccharide and / or a salt thereof is a hyaluronic acid oligosaccharide and / or a salt thereof in which the pyranose skeleton of all constituent monosaccharides is formed by a single bond. The unsaturated hyaluronic acid oligosaccharide and / or salt thereof is hyaluronic acid oligosaccharide and / or salt thereof in which a double bond is contained in the pyranose skeleton of at least one constituent monosaccharide. As the unsaturated hyaluronic acid oligosaccharide and / or salt thereof, specifically, the hydroxyl group bonded to the 4-position carbon atom of glucuronic acid located at the non-reducing end is removed, and the 4-position carbon atom is removed. There are hyaluronic acid oligosaccharides and / or salts thereof in which the carbon atom at position 5 is bonded by a double bond.
ヒアルロン酸オリゴ糖及び/又はその塩は、ヒアルロン酸を加水分解することによって製造することができ、また、酵素反応、化学合成、微生物培養等によって製造することもできる。ヒアルロン酸を加水分解してヒアルロン酸オリゴ糖及び/又はその塩を製造する方法としては、例えば、酵素分解法、アルカリ分解法、加熱処理法、超音波処理法等の公知の方法が挙げられる。具体的には、酵素分解法としては、ヒアルロン酸分解酵素(ヒアルロニダーゼ(睾丸由来)、ヒアルロニダーゼ(Streptomyces由来)、ヒアルロニダーゼSDなど)等のヒアルロン酸加水分解酵素で、ヒアルロン酸を分解する方法が挙げられる。また、アルカリ分解法としては、具体的には、ヒアルロン酸を含む水溶液に1N程度の水酸化ナトリウム等の塩基を加え、数時間加温して、低分子化させる方法等が挙げられる。更に、微生物培養によって製造する方法としては、例えば、ヒアルロン酸及び/又はその塩の水溶液中で、ヒアルロン酸及び/又はその塩の分解能を有する微生物(例えば、Streptomyces、Streptococcus、Peptococcus、Arthrobacter、Proteus、Flavobacterium等)を培養する方法が挙げられる。 Hyaluronic acid oligosaccharides and / or salts thereof can be produced by hydrolyzing hyaluronic acid, and can also be produced by enzymatic reaction, chemical synthesis, microbial culture, and the like. Examples of the method for producing hyaluronic acid oligosaccharide and / or a salt thereof by hydrolyzing hyaluronic acid include known methods such as an enzymatic decomposition method, an alkali decomposition method, a heat treatment method, and an ultrasonic treatment method. Specifically, the enzymatic degradation method includes a method of degrading hyaluronic acid with a hyaluronic acid hydrolase such as hyaluronic acid degrading enzyme (hyaluronidase (derived from testicles), hyaluronidase (derived from Streptomyces), hyaluronidase SD, etc.). . Specific examples of the alkali decomposition method include a method of adding a base such as 1N sodium hydroxide to an aqueous solution containing hyaluronic acid and heating it for several hours to lower the molecular weight. Furthermore, as a method for producing by microbial culture, for example, in an aqueous solution of hyaluronic acid and / or a salt thereof, a microorganism having a resolution of hyaluronic acid and / or a salt thereof (for example, Streptomyces, Streptococcus, Peptococcus, Arthrobacter, Proteus, The method of culture | cultivating Flavobacterium etc. is mentioned.
ヒアルロン酸オリゴ糖及び/又はその塩は市販されており、本発明では、市販品を使用してもよい。ヒアルロン酸オリゴ糖及び/又はその塩の市販品としては、具体的には、飽和型のヒアルロン酸オリゴ糖及び/又はその塩としては、商品名「ヒアルロン酸オリゴ糖6糖」(株式会社糖質科学研究所)、商品名「ヒアルロン酸オリゴ糖8糖」(株式会社糖質科学研究所)、商品名「ヒアルロン酸オリゴ糖10糖」(株式会社糖質科学研究所)、商品名「ヒアルロン酸オリゴ糖12糖」(株式会社糖質科学研究所)、商品名「Hyaluronic Acid Oligosaccharide」(2糖と4糖の混合物、AdipoGen社製)、商品名「Hyaluronic Acid Oligosaccharide」(4〜8糖の混合物、AdipoGen社製)、商品名「Hyaluronic Acid Oligosaccharide(<1.5kDa)」(2糖と4糖の混合物、AdipoGen社製)、商品名「マイクロヒアルロン酸FCH」((12〜14糖の混合物、キッコーマンバイオケミファ社製)等が挙げられる。また、不飽和型のヒアルロン酸オリゴ糖及び/又はその塩としては、具体的には、商品名「Hyaluronic Acid Oligosaccharide,dp2」(Iduron Ltd製)、商品名「Hyaluronic Acid Oligosaccharide,dp4」(Iduron Ltd製)、商品名「Hyaluronic Acid Oligosaccharide,dp6」(Iduron Ltd製)、商品名「Hyaluronic Acid Oligosaccharide,dp8」(Iduron Ltd製)、商品名「Hyaluronic Acid Oligosaccharide,dp10」(Iduron Ltd製)、商品名「Hyaluronic Acid Oligosaccharide,dp12」(Iduron Ltd製)、商品名「Hyaluronic Acid Oligosaccharide,dp14」(Iduron Ltd製)、商品名「Hyaluronic Acid Oligosaccharide,dp18」(Iduron Ltd製)、商品名「Hyaluronic Acid Oligosaccharide,dp20」(Iduron Ltd製)等が挙げられる。 Hyaluronic acid oligosaccharides and / or salts thereof are commercially available. In the present invention, commercially available products may be used. As a commercial product of hyaluronic acid oligosaccharide and / or a salt thereof, specifically, as a saturated hyaluronic acid oligosaccharide and / or a salt thereof, the trade name “hyaluronic acid oligosaccharide hexasaccharide” (Carbohydrate Co., Ltd.) Scientific Research Laboratories), trade name "Hyaluronic Acid Oligosaccharide Octasaccharide" (Glucose Science Laboratories, Inc.), trade name "Hyaluronic Acid Oligosaccharide 10 Sugar" (Glucose Science Laboratories, Inc.) Oligosaccharide 12 sugars (Glycochemical Research Institute, Inc.), trade name "Hyaluronic Acid Oligosaccharide" (mixture of disaccharides and tetrasaccharides, manufactured by AdipoGen), trade name "Hyaluronic Acid Oligosaccharide" (mixture of 4 to 8 sugars , AdipoGen), trade name "Hyaluronic Acid Oligosacchar de (<1.5 kDa) (a mixture of disaccharides and tetrasaccharides, manufactured by AdipoGen), trade name “micro hyaluronic acid FCH” (a mixture of 12 to 14 saccharides, manufactured by Kikkoman Biochemifa), and the like. Further, as the unsaturated hyaluronic acid oligosaccharide and / or a salt thereof, specifically, the trade name “Hyaluronic Acid Oligosaccharide, dp2” (manufactured by Iduron Ltd), the trade name “Hyaluronic Acid Oligosaccharide, dp4” (IduronLt) ), Trade name “Hyaluronic Acid Oligosaccharide, dp6” (manufactured by Iduron Ltd), trade name “Hyaluronic Acid Oligosaccharide, dp8” (Iduron) Ltd.), trade name “Hyaluronic Acid Oligosaccharide, dp10” (manufactured by Iduron Ltd), trade name “Hyaluronic Acid Oligosaccharide, dp12” (manufactured by Iduronic Ltd), trade name “Hyaluronidac14” Name “Hyaluronic Acid Oligosaccharide, dp 18” (manufactured by Iduron Ltd.), trade name “Hyaluronic Acid Oligosaccharide, dp 20” (manufactured by Iduron Ltd), and the like.
本発明の外用組成物において、(B)成分として、ヒアルロン酸オリゴ糖又はその塩のいずれか一方を単独で使用してもよく、またこれらを組み合わせて使用してもよい。 In the composition for external use of the present invention, as the component (B), either one of hyaluronic acid oligosaccharide or a salt thereof may be used alone, or these may be used in combination.
本発明の外用組成物において、(B)成分の濃度については、特に制限されないが、例えば0.0001〜1.5重量%が挙げられる。重厚な塗布感、保湿感、伸ばし易さ、及びべたつき抑制をより一層効果的に向上させるという観点から、(B)成分の濃度として、好ましくは0.0001〜1重量%、更に好ましくは0.00025〜1重量%、特に好ましくは0.001〜1重量%が挙げられる。 The concentration of the component (B) in the composition for external use of the present invention is not particularly limited, and, for example, 0.0001 to 1.5% by weight can be mentioned. The concentration of the component (B) is preferably 0.0001 to 1% by weight, more preferably 0.1 to 1% by weight, from the viewpoint of more effectively improving heavy coating feeling, moisturizing feeling, ease of stretching, and suppression of stickiness. There may be mentioned 0,025 to 1% by weight, particularly preferably 0.001 to 1% by weight.
また、本発明の外用組成物において、(A)成分と(B)成分の比率については、特に制限されないが、重厚な塗布感、保湿感、伸ばし易さ、及びべたつき抑制をより一層効果的に向上させるという観点から、(A)成分100重量部当たり、(B)成分が、好ましくは0.1重量部以上、更に好ましくは0.1〜300重量部が挙げられる。また、(A)成分が、(B)成分の同量以上、即ち、(A)成分100重量部当たり、(B)成分が100重量部以下、好ましくは0.1〜100重量部、更に好ましくは0.1〜80重量部、特に好ましくは0.1〜50重量部を充足する場合には、(A)成分の溶解性がより一層向上する傾向が見られると共に、格段に優れた重厚な塗布感及び保湿感を備えさせることが可能になる。 Further, in the composition for external use of the present invention, the ratio of the component (A) to the component (B) is not particularly limited, but it is more effective to prevent heavy coating feeling, moisturizing feeling, stretchability, and stickiness suppression. From the viewpoint of improvement, the component (B) is preferably 0.1 parts by weight or more, more preferably 0.1 to 300 parts by weight, per 100 parts by weight of the component (A). The component (A) is not less than the same amount as the component (B), that is, 100 parts by weight or less of the component (B) per 100 parts by weight of the component (A), preferably 0.1 to 100 parts by weight, When 0.1 to 80 parts by weight, particularly preferably 0.1 to 50 parts by weight is satisfied, the solubility of the component (A) tends to be further improved, and the remarkably excellent heavy It becomes possible to provide a feeling of application and a feeling of moisture.
(C)低分子ヒアルロン酸及び/又はその塩
本発明の外用組成物は、前記(A)及び(B)成分に加えて、低分子化ヒアルロン酸及び/又はその塩((C)成分と表記することもある)を含んでいてもよい。このような低分子化ヒアルロン酸及び/又はその塩を配合することによって、重厚な塗布感、保湿感、及び伸ばし易さ、特に重厚な塗布感をより一層効果的に向上させることが可能にある。
(C) Low-molecular-weight hyaluronic acid and / or a salt thereof The composition for external use of the present invention comprises, in addition to the components (A) and (B), a low-molecular-weight hyaluronic acid and / or a salt thereof ((C) component May be included). By blending such a low molecular weight hyaluronic acid and / or salt thereof, it is possible to more effectively improve the heavy coating feeling, moisturizing feeling, and easiness of extension, especially the heavy coating feeling. .
本発明で使用される低分子ヒアルロン酸の塩については、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、ナトリウム塩、カリウム塩等のアルカリ金属塩;カルシウム塩、マグネシウム塩などのアルカリ土類金属塩;トリ(n−ブチル)アミン塩、トリエチルアミン塩、ピリジン塩、アミノ酸塩等のアミン塩等が挙げられる。これらの低分子ヒアルロン酸の塩の中でも、好ましくはアルカリ金属塩、更に好ましくはナトリウム塩が挙げられる。これらの低分子ヒアルロン酸の塩は、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 salt of the low molecular weight hyaluronic acid used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, but examples thereof include alkali metal salts such as sodium salt and potassium salt; calcium salt and magnesium salt, etc. Examples include alkaline earth metal salts; amine salts such as tri (n-butyl) amine salts, triethylamine salts, pyridine salts, amino acid salts, and the like. Among these salts of low molecular weight hyaluronic acid, preferred are alkali metal salts, more preferably sodium salts. These low molecular hyaluronic acid salts may be used alone or in combination of two or more.
本発明で使用される低分子ヒアルロン酸及び/又はその塩の平均分子量は、通常8千〜12万程度であればよいが、好ましくは5万〜12万が挙げられる。本発明において、低分子ヒアルロン酸及び/又はその塩の平均分子量は、ゲル濾過クロマトグラフィー(GPC)法によって、プルランを標準物質として使用して求められる重量平均分子量である。 The average molecular weight of the low molecular weight hyaluronic acid and / or the salt thereof to be used in the present invention may be usually about 8,000 to 120,000, and preferably 50,000 to 120,000. In the present invention, the average molecular weight of the low molecular weight hyaluronic acid and / or a salt thereof is a weight average molecular weight obtained by using gel pull chromatography (GPC) method using pullulan as a standard substance.
低分子ヒアルロン酸及び/又はその塩は、ヒアルロン酸を加水分解することによって製造することができ、また、酵素反応、化学合成、微生物培養等によって製造することもできる。 Low molecular hyaluronic acid and / or a salt thereof can be produced by hydrolyzing hyaluronic acid, and can also be produced by enzymatic reaction, chemical synthesis, microbial culture, or the like.
低分子ヒアルロン酸及び/又はその塩は市販されており、本発明では、市販されているものを使用してもよい。低分子ヒアルロン酸及び/又はその塩の市販品としては、具体的には、商品名「ヒアロオリゴ」(平均分子量1万以下、キユーピー株式会社)、商品名「ヒアルロン酸FCH−SU」(平均分子量5〜11万、キッコーマンバイオケミファ株式会社)、商品名「ヒアルロン酸(L)」(平均分子量5万以下、株式会社FAPジャパン)、商品名「ヒアルロン酸(SL)」(平均分子量1万以下、株式会社FAPジャパン)等が挙げられる。 Low molecular weight hyaluronic acid and / or salts thereof are commercially available, and in the present invention, commercially available ones may be used. Specifically, as a commercial product of low molecular weight hyaluronic acid and / or a salt thereof, specifically, trade name "hyalooligo" (average molecular weight 10,000 or less, Kewpie Corporation), trade name "hyaluronic acid FCH-SU" (average molecular weight 5 ~ 110,000, Kikkoman Biochemifa Co., Ltd., trade name "hyaluronic acid (L)" (average molecular weight 50,000 or less, FAP Japan Co., Ltd.), trade name "hyaluronic acid (SL)" (average molecular weight 10,000 or less, stock Company FAP Japan) etc.
本発明の外用組成物において、(C)成分として、低分子ヒアルロン酸又はその塩のいずれか一方を単独で使用してもよく、またこれらを組み合わせて使用してもよい。 In the composition for external use of the present invention, either low molecular weight hyaluronic acid or a salt thereof may be used alone as the component (C), or these may be used in combination.
本発明の外用組成物において、低分子ヒアルロン酸及び/又はその塩の濃度については、特に制限されないが、例えば0.001〜3重量%が挙げられる。重厚な塗布感、保湿感、及び伸ばし易さ、特に濃厚な塗布感をより一層効果的に向上させるという観点から、低分子ヒアルロン酸及び/又はその塩の濃度として、好ましくは0.002〜2重量%、更に好ましくは0.002〜1重量%が挙げられる。 In the composition for external use of the present invention, the concentration of the low molecular weight hyaluronic acid and / or the salt thereof is not particularly limited, and, for example, 0.001 to 3% by weight can be mentioned. From the viewpoint of more effectively improving the heavy coating feeling, moisturizing feeling, and easiness of extension, particularly the thick coating feeling, the concentration of the low-molecular hyaluronic acid and / or salt thereof is preferably 0.002 to 2. % By weight, more preferably 0.002 to 1% by weight.
また、本発明の外用組成物において、ヒアルロン酸及び/又はその塩と低分子ヒアルロン酸及び/又はその塩との比率については、特に制限されないが、重厚な塗布感、保湿感、及び伸ばし易さ、特に濃厚な塗布感をより一層効果的に向上させるという観点から、ヒアルロン酸及び/又はその塩の総量100重量部当たり、低分子ヒアルロン酸及び/又はその塩の総量が、好ましくは0.1〜300重量部、更に好ましくは0.2〜200重量部、更に好ましくは0.5〜150重量部、特に好ましくは1〜100重量部が挙げられる。 Further, in the composition for external use of the present invention, the ratio of hyaluronic acid and / or a salt thereof to low molecular weight hyaluronic acid and / or a salt thereof is not particularly limited, but heavy coating feeling, moisturizing feeling, and ease of stretching In particular, from the viewpoint of more effectively improving the dense coating feeling, the total amount of low molecular weight hyaluronic acid and / or its salt is preferably 0.1 per 100 parts by weight of the total amount of hyaluronic acid and / or its salt. The amount is preferably 300 to 300 parts by weight, more preferably 0.2 to 200 parts by weight, still more preferably 0.5 to 150 parts by weight, and particularly preferably 1 to 100 parts by weight.
水
本発明の外用組成物は、水を基剤として用いて所望の剤型に調製される。本発明の外用組成物において、水の濃度については、外用組成物の剤型等に応じて適宜設定すればよいが、例えば20〜99.9重量%、好ましくは30〜99.9重量%、更に好ましくは35〜99.9重量%が挙げられる。
Composition for external use of the water present invention, water used as a base is prepared in the desired dosage form. In the composition for external use of the present invention, the concentration of water may be appropriately set according to the type of the composition for external use, etc., but for example 20 to 99.9% by weight, preferably 30 to 99.9% by weight More preferably, 35-99.9 weight% is mentioned.
その他の成分
本発明の外用組成物は、前述する成分の他に、必要に応じて、生理学的に有用な機能性を示す機能性成分が含まれていてもよい。このような機能性成分としては、化粧料や外用医薬品等に配合可能なものであることを限度として特に制限されないが、例えば、水溶性のビタミン類、油溶性のビタミン類、酵素、ペプチド、アミノ酸、ホルモン、各種サイトカイン、各種動植物抽出物、ステロイド剤、保湿剤、美白剤、生薬、抗ヒスタミン剤、収斂剤、細胞賦活剤、角質軟化剤、局所麻酔剤、抗炎症剤、酸化防止剤、抗菌剤、鎮痒剤、皮膚保護剤、血行促進剤、ステロール類等が挙げられる。
Other Components The composition for external use of the present invention may contain, in addition to the components described above, functional components exhibiting physiologically useful functionality, as necessary. Such functional components are not particularly limited as long as they can be added to cosmetics and external medicines, but, for example, water-soluble vitamins, oil-soluble vitamins, enzymes, peptides, amino acids , Hormones, various cytokines, various animal and plant extracts, steroids, moisturizers, whitening agents, crude drugs, antihistamines, astringents, cell activators, keratin softeners, local anesthetics, anti-inflammatory agents, antioxidants, antibacterial agents, Antipruritic agents, skin protectants, blood circulation enhancers, sterols and the like can be mentioned.
また、本発明の外用組成物は、前述する成分の他に、所望の剤型に調製するために、他の基剤や添加剤が含まれていてもよい。このような基剤や添加剤としては、化粧料や外用医薬品等に配合可能でものであることを限度として特に制限されないが、例えば、油性成分、低級アルコール、界面活性剤、防腐剤、増粘剤、香料、顔料、緩衝剤、pH調整剤等が挙げられる。 In addition to the components described above, the external composition of the present invention may further contain other bases and additives in order to prepare a desired dosage form. Such bases and additives are not particularly limited as long as they can be incorporated into cosmetics and external medicines, etc., but, for example, oily components, lower alcohols, surfactants, preservatives, thickeners , Perfumes, pigments, buffers, pH adjusters and the like.
油性成分としては、動物油、植物油、合成油等の起源や、固形油、半固形油、液体油、揮発性油等の性状を問わず、例えば、炭化水素類、油脂類、高級アルコール類、ロウ類、硬化油類、エステル油類、脂肪酸類、フッ素系油類、ラノリン誘導体類、油性ゲル化剤類、油溶性紫外線吸収剤類等が挙げられる。油性成分として、具体的には、流動パラフィン、スクワラン、ワセリン、ポリイソブチレン、ポリブテン、パラフィンワックス、セレシンワックス、マイクロクリスタリンワックス、フィッシャトロプスワックス等の炭化水素類;オリーブ油、ヒマシ油、ホホバ油、ミンク油、マカデミアンナッツ油等の油脂類;ミツロウ、カルナウバワックス、キャンデリラワックス、ゲイロウ、モクロウ、モンタンワックス等のロウ類;2−エチルヘキサン酸セチル、イソステアリン酸イソトリデシル、ミリスチン酸イソプロピル、パルミチン酸イソプロピル、ミリスチン酸オクチルドデシル、トリオクタン酸セチル、トリ2−エチルヘキサン酸グリセリル、ジイソステアリン酸ポリグリセリル、トリイソステアリン酸ジグリセリル、トリベヘン酸グリセリル、ロジン酸ペンタエリトリットエステル、ジオクタン酸ネオペンチルグリコール、リンゴ酸ジイソステアリル、コレステロール脂肪酸エステル、N−ラウロイル−L−グルタミン酸ジ(コレステリル・ベヘニル・オクチルドデシル)、マカデミアンナッツ脂肪酸フィトステリル等のエステル類;ステアリン酸、ラウリン酸、ミリスチン酸、ベヘニン酸、イソステアリン酸、オレイン酸等の脂肪酸類;セチルアルコール、ステアリルアルコール、セトステアリルアルコール、ベヘニルアルコール等の高級アルコール類;パーフルオロポリエーテル、パーフルオロデカン、パーフルオロオクタン等のフッ素系油剤類;ラノリン、酢酸ラノリン、ラノリン脂肪酸イソプロピル、ラノリンアルコール等のラノリン誘導体;デキストリン脂肪酸エステル、蔗糖脂肪酸エステル、デンプン脂肪酸エステル、12−ヒドロキシステアリン酸、ステアリン酸アルミニウム、ステアリン酸カルシウム等の油性ゲル化剤類;パラアミノ安息香酸エチル、パラメトキシケイ皮酸−2−エチルヘキシル、4−tert−ブチル−4’−メトキシジベンゾイルメタン、オクチルトリアゾン、ビスエチルヘキシルオキシフェノールメトキシフェニルトリアジン、ジエチルアミノヒドロキシベンゾイル安息香酸ヘキシル、メチレンビスベンゾトリアゾリルテトラメチルブチルフェノール、オキシベンゾン等の油溶性紫外線吸収剤類等が挙げられる。これらの油性成分は、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。 As the oil component, regardless of the origin of animal oil, vegetable oil, synthetic oil, etc., and properties of solid oil, semi-solid oil, liquid oil, volatile oil, etc., for example, hydrocarbons, fats and oils, higher alcohols, wax And hydrogenated oils, ester oils, fatty acids, fluorine-based oils, lanolin derivatives, oily gelling agents, oil-soluble ultraviolet light absorbers, and the like. Specific examples of oil components include hydrocarbons such as liquid paraffin, squalane, petrolatum, polyisobutylene, polybutene, paraffin wax, ceresin wax, microcrystalline wax, and fisher trops wax; olive oil, castor oil, jojoba oil, mink Oils and fats such as macadamian nut oil; waxes such as beeswax, carnauba wax, candelilla wax, gay wax, moclaw and montan wax; cetyl 2-ethylhexanoate, isotridecyl isostearate, isopropyl myristate, isopropyl palmitate Octyldodecyl myristate, cetyl trioctanoate, glyceryl tri-2-ethylhexanoate, polyglyceryl diisostearate, diglyceryl triisostearate, glyce tribehenate , Rosin acid pentaerythritol ester, neopentyl glycol dioctanoate, diisostearyl malate, cholesterol fatty acid ester, N-lauroyl-L-glutamate di (cholesteryl, behenyl, octyldodecyl), esters of macadamian nut fatty acid phytosteryl, etc. Fatty acids such as stearic acid, lauric acid, myristic acid, behenic acid, isostearic acid, oleic acid; higher alcohols such as cetyl alcohol, stearyl alcohol, cetostearyl alcohol, behenyl alcohol; perfluoropolyethers, perfluorodecane, Fluorine-based oil agents such as perfluorooctane; lanolin derivatives such as lanolin, lanolin acetate, lanolin fatty acid isopropyl and lanolin alcohol; dextrin fatty acid S Oily gelling agents such as sucrose fatty acid ester, starch fatty acid ester, 12-hydroxystearic acid, aluminum stearate, calcium stearate; ethyl paraaminobenzoate, 2-ethylhexyl paramethoxycinnamate, 4-tert-butyl -4'-methoxydibenzoylmethane, octyltriazone, bisethylhexyloxyphenol methoxyphenyltriazine, hexyl diethylaminohydroxybenzoyl benzoate, methylenebisbenzotriazolyltetramethylbutylphenol, oxybenzone, etc. It is done. These oily components may be used alone or in combination of two or more.
低級アルコールとしては、例えば、エタノール、イソプロパノール等の低級1価アルコール;プロピレングリコール、1,3−ブチレングリコール、ジプロピレングリコール、ポリエチレングリコール、グリセリン、ジグリセリン、ポリグリセリン等の多価アルコール、1,2−ペンタンジオール等挙げられる。これらの低級アルコールは、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。 Examples of lower alcohols include lower monohydric alcohols such as ethanol and isopropanol; polyhydric alcohols such as propylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, glycerin, diglycerin and polyglycerin; -Pentanediol and the like. These lower alcohols may be used alone or in combination of two or more.
界面活性剤としては、非イオン性界面活性剤、アニオン性界面活性剤、カチオン性界面活性剤、両性界面活性剤等が挙げられる。 As surfactant, nonionic surfactant, anionic surfactant, cationic surfactant, amphoteric surfactant etc. are mentioned.
非イオン性界面活性剤としては、具体的には、ソルビタン脂肪酸エステル類(例えば、ソルビタンモノオレート、ソルビタンモノイソステアレート、ソルビタンモノラウレート、ソルビタンモノパルミテート、ソルビタンモノステアレート、ソルビタンセスキオレエート、ソルビタントリオレエート、ペンタ−2−エチルヘキシル酸ジグリセロールソルビタン、テトラ−2−エチルヘキシル酸ジグリセロールソルビタン等);グリセリンポリグリセリン脂肪酸類(例えば、モノ綿実油脂肪酸グリセリン、モノエルカ酸グリセリン、セスキオレイン酸グリセリン、モノステアリン酸グリセリン、α,α’−オレイン酸ピログルタミン酸グリセリン、モノステアリン酸グリセリンリンゴ酸等);プロピレングリコール脂肪酸エステル類(例えば、モノステアリン酸プロピレングリコール等);硬化ヒマシ油誘導体;グリセリンアルキルエーテル、POE−ソルビタン脂肪酸エステル類(例えば、POE−ソルビタンモノオレート、POE−ソルビタンモノステアレート、POE−ソルビタンモノオレート、POE−ソルビタンテトラオレエート等);POEソルビット脂肪酸エステル類(例えば、POE−ソルビットモノラウレート、POE−ソルビットモノオレエート、POE−ソルビットペンタオレエート、POE−ソルビットモノステアレート等);POE−グリセリン脂肪酸エステル類(例えば、POE−グリセリンモノステアレート、POE−グリセリンモノイソステアレート、POE−グリセリントリイソステアレート等のPOE−モノオレエート等);POE−脂肪酸エステル類(例えば、POE−ジステアレート、POE−モノジオレエート、ジステアリン酸エチレングリコール等);POE−アルキルエーテル類(例えば、POE−ラウリルエーテル、POE−オレイルエーテル、POE−ステアリルエーテル、POE−ベヘニルエーテル、POE−2−オクチルドデシルエーテル、POE−コレスタノールエーテル等);プルロニック型類(例えば、プルロニック等);POE・POP−アルキルエーテル類(例えば、POE・POP−セチルエーテル、POE・POP−2−デシルテトラデシルエーテル、POE・POP−モノブチルエーテル、POE・POP−水添ラノリン、POE・POP−グリセリンエーテル等);テトラPOE・テトラPOP−エチレンジアミン縮合物類(例えば、テトロニック等);POE−ヒマシ油硬化ヒマシ油誘導体(例えば、POE−ヒマシ油、POE−硬化ヒマシ油、POE−硬化ヒマシ油モノイソステアレート、POE−硬化ヒマシ油トリイソステアレート、POE−硬化ヒマシ油モノピログルタミン酸モノイソステアリン酸ジエステル、POE−硬化ヒマシ油マレイン酸等);アルカノールアミド(例えば、ヤシ油脂肪酸ジエタノールアミド、ラウリン酸モノエタノールアミド、脂肪酸イソプロパノールアミド等);ショ糖脂肪酸エステル;アルキルエトキシジメチルアミンオキシド;トリオレイルリン酸等が挙げられる。 Specific examples of the nonionic surfactant include sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate). Sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate); glycerin polyglycerin fatty acids (eg mono cottonseed oil fatty acid glycerin, monoerucic acid glycerin, sesquioleate glycerin, mono Glyceryl stearate, α, α′-oleic acid pyroglutamate glycerin, monostearate glycerin malate, etc.); propylene glycol fatty acid esters (eg, Propylene glycol nostearate); hardened castor oil derivative; glycerin alkyl ether, POE-sorbitan fatty acid esters (for example, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraole) POE sorbite fatty acid esters (eg, POE-sorbite monolaurate, POE-sorbite monooleate, POE-sorbite pentaoleate, POE-sorbite monostearate, etc.); POE-glycerin fatty acid esters (eg, POE-glycerin monostearate, POE-glycerin monoisostearate, POE-glyceryl triisostearate etc. POE-monooleate etc.); POE-fatty acid ester (For example, POE-distearate, POE-monodiolate, ethylene glycol distearate, etc.); POE-alkyl ethers (for example, POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE- 2-octyldodecyl ether, POE-cholestanol ether etc.); Pluronic types (eg, Pluronic etc.); POE • POP-alkyl ethers (eg, POE • POP-cetyl ether, POE • POP-2-decyl tetradecyl) Ether, POE.POP-monobutyl ether, POE.POP-hydrogenated lanolin, POE.POP-glycerin ether, etc .; tetra POE. Tetra POP-ethylene diamine condensates (eg, tetronyl) POE-castor oil hardened castor oil derivatives (for example, POE-castor oil, POE-hardened castor oil, POE-hardened castor oil monoisostearate, POE-hardened castor oil triisostearate, POE-hardened castor oil) Monopyroglutamic acid monoisostearic acid diester, POE-hardened castor oil maleic acid, etc.); alkanolamide (for example, coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc.); sucrose fatty acid ester; alkylethoxydimethylamine Oxides; trioleyl phosphate and the like.
アニオン性界面活性剤としては、具体的には、脂肪酸セッケン(例えば、ラウリン酸ナトリウム、パルミチン酸ナトリウム等);高級アルキル硫酸エステル塩(例えば、ラウリル硫酸ナトリウム、ラウリル硫酸カリウム等);アルキルエーテル硫酸エステル塩(例えば、POE−ラウリル硫酸トリエタノールアミン、POE−ラウリル硫酸ナトリウム等);N−アシルサルコシン酸(例えば、ラウロイルサルコシンナトリウム等);高級脂肪酸アミドスルホン酸塩(例えば、N−ミリストイル−N−メチルタウリンナトリウム、ヤシ油脂肪酸メチルタウリンナトリウム、ラウリルメチルタウリンナトリウム等);スルホコハク酸塩(例えば、ジ−2−エチルヘキシルスルホコハク酸ナトリウム、モノラウロイルモノエタノールアミドポリオキシエチレンスルホコハク酸ナトリウム、ラウリルポリプロピレングリコールスルホコハク酸ナトリウム等);アルキルベンゼンスルホン酸塩(例えば、リニアドデシルベンゼンスルホン酸ナトリウム、リニアドデシルベンゼンスルホン酸トリエタノールアミン、リニアドデシルベンゼンスルホン酸等);高級脂肪酸エステル硫酸エステル塩(例えば、硬化ヤシ油脂肪酸グリセリン硫酸ナトリウム等);N−アシルグルタミン酸塩(例えば、N−ラウロイルグルタミン酸モノナトリウム、N−ステアロイルグルタミン酸ジナトリウム、N−ミリストイル−L−グルタミン酸モノナトリウム等);POE−アルキルエーテルカルボン酸;POE−アルキルアリルエーテルカルボン酸塩;α−オレフィンスルホン酸塩;ラウロイルモノエタノールアミドコハク酸ナトリウム;N−パルミトイルアスパラギン酸ジトリエタノールアミン等が挙げられる。 Specific examples of the anionic surfactant include fatty acid soaps (eg, sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (eg, sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates Salts (eg, POE-lauryl sulfate triethanolamine, POE-sodium lauryl sulfate, etc.); N-acyl sarcosic acids (eg, lauroyl sarcosine sodium etc.); higher fatty acid amido sulfonates (eg, N-myristoyl-N-methyl) Sodium taurine, coconut oil fatty acid methyl taurine sodium, lauryl methyl taurine sodium etc .; sulfosuccinates (eg sodium di-2-ethylhexyl sulfosuccinate, monolauroyl monoethanolamide polyoxy) Sodium ethylene sulfosuccinate, lauryl polypropylene glycol sodium sulfosuccinate etc .; alkyl benzene sulfonate (eg, sodium linear dodecyl benzene sulfonate, triethanolamine linear dodecyl benzene sulfonate, linear dodecyl benzene sulfonic acid, etc.), higher fatty acid ester sulfate ester Salts (eg, hardened coconut oil fatty acid glycerin sodium sulfate etc.); N-acyl glutamates (eg N-lauroylglutamic acid monosodium, N-stearoylglutamic acid disodium, N-myristoyl-L-glutamic acid monosodium etc); POE- Alkyl ether carboxylic acid; POE-alkyl allyl ether carboxylate; α-olefin sulfonate; lauroyl monoethanolamine Sodium dosuccinate; N-palmitoyl aspartic acid ditriethanolamine etc. are mentioned.
カチオン性界面活性剤としては、具体的には、アルキルトリメチルアンモニウム塩(例えば、塩化ステアリルトリメチルアンモニウム、塩化ラウリルトリメチルアンモニウム等);アルキルピリジニウム塩(例えば、塩化セチルピリジニウム等);塩化ジステアリルジメチルアンモニウムジアルキルジメチルアンモニウム塩;塩化ポリ(N,N’−ジメチル−3,5−メチレンピペリジニウム);アルキル四級アンモニウム塩;アルキルジメチルベンジルアンモニウム塩;アルキルイソキノリニウム塩;ジアルキルモリホニウム塩;塩化ベンザルコニウム;塩化ベンゼトニウム等が挙げられる。 Specific examples of the cationic surfactant include alkyl trimethyl ammonium salts (for example, stearyl trimethyl ammonium chloride, lauryl trimethyl ammonium chloride and the like); alkyl pyridinium salts (for example, cetyl pyridinium chloride and the like); distearyl dimethyl ammonium dialkyl chloride Dimethyl ammonium salt; poly (N, N'-dimethyl-3,5-methylene piperidinium chloride); alkyl quaternary ammonium salt; alkyl dimethyl benzyl ammonium salt; alkyl isoquinolinium salt; Benzalkonium; benzethonium chloride and the like.
両性界面活性剤としては、例えば、イミダゾリン系両性界面活性剤(例えば、2−ウンデシル−N,N,N−(ヒドロキシエチルカルボキシメチル)−2−イミダゾリンナトリウム、2−ココイル−2−イミダゾリニウムヒドロキサイド−1−カルボキシエチロキシ2ナトリウム塩等);ベタイン系界面活性剤(例えば、2−ヘプタデシル−N−カルボキシメチル−N−ヒドロキシエチルイミダゾリニウムベタイン、アミドアミン型両性界面活性剤、ラウリルジメチルアミノ酢酸ベタイン、アルキルベタイン、アミドベタイン、スルホベタイン等)等が挙げられる。 Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (eg, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide). Side-1-carboxyethyloxy disodium salt and the like); betaine surfactants (eg, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, amidoamine type amphoteric surfactant, lauryl dimethylamino acetic acid And betaines, alkyl betaines, amido betaines, sulfobetaines etc.
これらの界面活性剤は、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。 These surfactants may be used alone or in combination of two or more.
防腐剤としては、例えば、パラオキシ安息香酸エステル、フェノキシエタノール、安息香酸、安息香酸ナトリウム、デヒドロ酢酸、デヒドロ酢酸ナトリウム、ベンジルアルコール、クロロブタノール、ソルビン酸及びその塩、グルコン酸クロルヘキシジン等が挙げられる。これらの防腐剤は、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。 Examples of the preservative include p-hydroxybenzoic acid ester, phenoxyethanol, benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, benzyl alcohol, chlorobutanol, sorbic acid and salts thereof, chlorhexidine gluconate and the like. These preservatives may be used alone or in combination of two or more.
増粘剤としては、例えば、メチルセルロース、エチルセルロース、ヒドロキシエチルセルロース、ヒドロキシメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロース、グアーガム、ローカストビーンガム、カラギーナン、キサンタンガム、ポリビニルアルコール、ポリビニルピロリドン、カルボキシビニルポリマー、アクリル酸メタクリル酸アルキル共重合体、ポリエチレングリコール、ベントナイト、アルギン酸、マクロゴール、コンドロイチン硫酸ナトリウム、カルボキシエチルセルロース等が挙げられる。これらの増粘剤は、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。 Examples of the thickener include methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, acrylic Examples thereof include alkyl methacrylate acid copolymer, polyethylene glycol, bentonite, alginic acid, macrogol, sodium chondroitin sulfate, carboxyethyl cellulose and the like. These thickeners may be used alone or in combination of two or more.
製造方法
本発明の外用組成物は、前記(A)及び(B)成分と共に、必要に応じて添加される(C)成分、他の機能性成分、基剤、添加剤等を混合し、所望の製剤形態に調製することによって得ることができる。
Production method The composition for external use according to the present invention is desired by mixing the components (A) and (B) with the component (C) added as needed, other functional components, a base, additives, etc. It can obtain by preparing to the formulation form.
また、前記(A)成分は、(B)成分によって水への溶解性が向上するので、本発明の外用組成物の製造において、(A)成分を水に溶解させる際に、(B)成分を共存させることが好ましい。(A)成分を水に溶解させる際に(B)成分を共存させる方法としては、例えば、(A)及び(B)成分を同時に水に添加する方法;水に(A)成分を添加し、(A)成分が溶解するまでに(B)成分を添加する方法;水に(B)成分を添加した後に(A)成分を添加する方法が挙げられる。 Further, since the component (A) is improved in solubility in water by the component (B), in the production of the composition for external use of the present invention, when the component (A) is dissolved in water, the component (B) Preferably coexist. As a method of coexisting component (B) when dissolving component (A) in water, for example, a method of simultaneously adding components (A) and (B) to water; adding component (A) to water, A method of adding the component (B) until the component (A) dissolves; a method of adding the component (A) after the component (B) is added to water.
剤型及び製剤形態
本発明の外用組成物は、液状、固形状、クリーム状、ジェル状等のいずれの剤型であってもよい。これらの剤型の中でも、液状の外用組成物は、重厚な塗布感、保湿感、伸ばし易さ、及びべたつき抑制等の効果を実感し易いため、本発明の外用組成物の剤型として好適である。
Dosage Form and Formulation Form The composition for external use of the present invention may be in any form such as liquid, solid, cream, or gel. Among these dosage forms, the liquid external composition is suitable as a dosage form of the external composition of the present invention because it can easily realize effects such as a heavy coating feeling, moisturizing feeling, easiness of stretching, and stickiness suppression. is there.
本発明の外用組成物は、化粧料、外用医薬品等の皮膚外用剤の製剤形態で使用される。本発明の外用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、化粧水、美容液、乳液、ジェル、口紅、ファンデーション等の化粧料;液剤(ローション剤、スプレー剤、エアゾール剤、及び乳液剤を含む)、フォーム剤、軟膏剤、クリーム剤、ジェル剤、貼付剤等の外用医薬品が挙げられる。これらの製剤形態の中でも、重厚な塗布感、保湿感、伸ばし易さ、及びべたつき抑制等の効果を実感させ易くするという観点から、好ましくは化粧料、更に好ましくは化粧水、美容液及び乳液が挙げられる。 The composition for external use of the present invention is used in the form of a preparation for external preparations for skin such as cosmetics and external medicines. The formulation form of the composition for external use according to the present invention is not particularly limited, but, for example, cosmetics such as cream, lotion, cosmetic solution, milk, gel, lipstick and foundation; liquid agent (lotion agent, spray agent, aerosol agent, And emulsions for external use), foams, ointments, creams, gels, patches and the like. Among these formulation forms, from the viewpoint of making it easy to realize effects such as heavy application feeling, moisturizing feeling, ease of stretching, and suppression of stickiness, cosmetics, preferably cosmetic liquids, cosmetic liquids and emulsions, are preferred. Can be mentioned.
2.ヒアルロン酸及び/又はその塩の溶解方法
前述するように、ヒアルロン酸オリゴ糖及び/又はその塩には、ヒアルロン酸及び/又はその塩の水への溶解性を向上させる作用がある。従って、本発明は、更に、ヒアルロン酸オリゴ糖及び/又はその塩((B)成分)の存在下で、ヒアルロン酸及び/又はその塩((A)成分)を水に溶解させることを特徴とする、ヒアルロン酸及び/又はその塩の溶解方法を提供する。
2. Method for Dissolving Hyaluronic Acid and / or Salt Thereof As described above, hyaluronic acid oligosaccharides and / or salts thereof have the effect of improving the solubility of hyaluronic acid and / or salts in water. Therefore, the present invention is further characterized by dissolving hyaluronic acid and / or a salt thereof (component (A)) in water in the presence of hyaluronic acid oligosaccharide and / or a salt thereof (component (B)). A method for dissolving hyaluronic acid and / or a salt thereof is provided.
本発明の溶解方法において、使用する(A)成分の種類、(B)成分の種類等については、前記「1.外用組成物」の欄に記載の通りである。 In the dissolution method of the present invention, the type of the component (A), the type of the component (B) and the like to be used are as described in the above-mentioned "1. Composition for external use".
本発明の溶解方法において、水に溶解させる(A)成分の最終濃度については、特に制限されず、例えば、0.01重量%以上、好ましくは0.03〜2重量%が挙げられる。特に、(A)成分の最終濃度を0.05重量%以上という高濃度にする場合には、ヒアルロン酸及び/又はその塩の添加量が多くなるため、従来技術では、溶解時に大きなダマが生じて溶解時間が長期化するという欠点がある。これに対して、本発明の溶解方法では、このような高濃度の(A)成分を溶解させる場合であっても、(A)成分の溶解性を向上させて溶解時間を短縮することができる。このような本発明の効果を鑑みれば、水に溶解させる(A)成分の最終濃度として、好ましくは0.05重量%以上、更に好ましくは0.05〜2重量%、特に好ましくは0.05〜1重量%が挙げられる。 In the dissolution method of the present invention, the final concentration of the component (A) to be dissolved in water is not particularly limited, and for example, 0.01% by weight or more, preferably 0.03 to 2% by weight can be mentioned. In particular, when the final concentration of component (A) is set to a high concentration of 0.05% by weight or more, the amount of addition of hyaluronic acid and / or its salt increases, so that the conventional technique causes a large amount of lumps during dissolution. And the dissolution time is prolonged. In contrast, the dissolution method of the present invention can improve the solubility of the component (A) and shorten the dissolution time even when dissolving such a high concentration of the component (A). . In view of the effects of the present invention, the final concentration of the component (A) to be dissolved in water is preferably 0.05% by weight or more, more preferably 0.05 to 2% by weight, particularly preferably 0.05 Up to 1% by weight.
また、本発明の溶解方法において、(B)成分の使用量については、特に制限されないが、水中での(B)成分の最終濃度が、例えば、0.0001〜1.5重量%、好ましくは0.0001〜1重量%、更に好ましくは0.00025〜1重量%、特に好ましくは0.001〜1重量%となる量が挙げられる。 In the dissolution method of the present invention, the amount of component (B) used is not particularly limited, but the final concentration of component (B) in water is, for example, 0.0001 to 1.5% by weight, preferably The amount is 0.0001 to 1% by weight, more preferably 0.00025 to 1% by weight, and particularly preferably 0.001 to 1% by weight.
本発明の溶解方法において、(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100重量部当たり、(B)成分が0.1重量部以上、好ましくは0.1〜300重量部であり、(A)成分の溶解性をより一層向上させるという観点から、更に好ましくは0.1〜100重量部、より好ましくは0.1〜80重量部、特に好ましくは0.1〜50重量部が挙げられる。 In the dissolution method of the present invention, the ratio of the component (A) and the component (B) is not particularly limited. For example, the component (B) is preferably 0.1 part by weight or more per 100 parts by weight of the component (A). Is from 0.1 to 300 parts by weight, and from the viewpoint of further improving the solubility of the component (A), more preferably 0.1 to 100 parts by weight, more preferably 0.1 to 80 parts by weight, in particular Preferably, 0.1 to 50 parts by weight can be mentioned.
本発明の溶解方法において、(B)成分の存在下で(A)成分を水に溶解させる手法としては、具体的には、(A)及び(B)成分を同時に水に添加する方法;水に(A)成分を添加し、(A)成分が溶解するまでに(B)成分を添加する方法;水に(B)成分を添加した後に(A)成分を添加する方法が挙げられる。 In the dissolution method of the present invention, as a technique for dissolving the component (A) in water in the presence of the component (B), specifically, a method of simultaneously adding the components (A) and (B) to water; (A) component is added to this, and (B) component is added until (A) component melt | dissolves; The method of adding (A) component after adding (B) component to water is mentioned.
本発明の溶解方法は、化粧料、医薬品、食品等のあらゆる分野において、(A)成分を水に溶解させた製品や原料を製造する際の(A)成分の溶解工程に用いることができる。特に、化粧料や外用医薬品等の外用組成物の製造時の(A)成分の溶解工程、とりわけ前記「1.外用組成物」の欄に示す外用組成物の製造時の(A)成分の溶解工程において、好適に用いられる。 The dissolution method of the present invention can be used in the dissolution step of the component (A) when producing a product or raw material in which the component (A) is dissolved in water in all fields such as cosmetics, pharmaceuticals, and foods. In particular, the step of dissolving the component (A) at the time of production of an external composition such as cosmetics and external medicines, especially the dissolution of the component (A) at the time of production of the external composition shown in the column of “1. It is suitably used in the process.
本発明の溶解方法において、(A)成分を溶解させる水には、(B)成分以外の成分が含まれていてもよい。例えば、本発明の溶解方法を、前記「1.外用組成物」の欄に示す外用組成物の製造時の(A)成分の溶解工程に用いる場合であれば、(A)成分を溶解させる水には、前記「1.外用組成物」の欄に記載の(C)成分、他の機能性成分、基剤、添加剤等が含まれていてもよい。 In the dissolution method of the present invention, the water for dissolving the component (A) may contain components other than the component (B). For example, if the dissolution method of the present invention is used in the step of dissolving the component (A) at the time of producing the external composition shown in the column of “1. External composition”, water for dissolving the component (A) The component (C) described in the section “1. Composition for external use”, other functional components, a base, additives and the like may be contained in the above.
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。 EXAMPLES The present invention will be more specifically described below by way of Examples, but the present invention is not limited thereto.
製造例:「不飽和型ヒアルロン酸オリゴ糖」の製造方法
以下に示す実施例及び比較例において、「不飽和型ヒアルロン酸オリゴ糖」は、特開2008−35858号公報に記載の方法に従って製造したものを使用した。具体的には、ヒアルロン酸ナトリウムの1重量%水溶液中で、アースロバクター アトロシアネウスJU-01(Arthrobacter atrocyaneus JU-01)株(独立行政法人製品評価技術基盤機構 特許微生物寄託センター 受託番号:NITE P−245)を25℃で120時間静置培養した。その後、0.22μmのメンブレンフィルターで当該菌株を除去し、凍結乾燥することにより不飽和型ヒアルロン酸オリゴ糖を得た。得られたヒアルロン酸オリゴ糖は、2糖(構成単糖数が2)であり、非還元末端に位置するグルクロン酸の4位の炭素原子に結合している水酸基が除去され、4位の炭素原子と5位の炭素原子が二重結合で結合している構造を有していた。
Production Example: Method for Producing “Unsaturated Hyaluronic Acid Oligosaccharide” In the following examples and comparative examples, “unsaturated hyaluronic acid oligosaccharide” was produced according to the method described in JP-A-2008-35858. I used something. Specifically, in a 1% by weight aqueous solution of sodium hyaluronate, Arthrobacter atrocyaneus JU-01 (Arthrobacter atrocyaneus JU-01) strain (National Institute of Technology and Evaluation, Patent Microbiology Depositary Center, Accession Number: NITE) P-245) was statically cultured at 25 ° C. for 120 hours. Thereafter, the strain was removed with a 0.22 μm membrane filter and lyophilized to obtain an unsaturated hyaluronic acid oligosaccharide. The obtained hyaluronic acid oligosaccharide is a disaccharide (the number of constituent monosaccharides is 2), the hydroxyl group bonded to the 4-position carbon atom of glucuronic acid located at the non-reducing end is removed, and the 4-position carbon is removed It had a structure in which the atom and the carbon atom at the 5-position were bonded by a double bond.
試験例1:ヒアルロン酸の水への溶解性の評価
表1に示す所定量のヒアルロン酸と不飽和型ヒアルロン酸オリゴ糖を添加した200mL容の容器に、室温の精製水を所定量添加(容器内の内容物の合計量100g)し、室温でプロペラ攪拌機にて500rpmの速度で撹拌を開始した。撹拌開始からヒアルロン酸のダマがなくなり、ヒアルロン酸が完全に溶解するまでの時間(溶解時間)を計測した。
Test Example 1: Evaluation of solubility of hyaluronic acid in water A predetermined amount of purified water at room temperature was added to a 200 mL container to which a predetermined amount of hyaluronic acid and unsaturated hyaluronic acid oligosaccharide shown in Table 1 were added (container The total amount of the content was 100 g) and stirring was started at room temperature with a propeller stirrer at a speed of 500 rpm. The time (dissolution time) from the start of stirring until hyaluronic acid was completely removed and hyaluronic acid was completely dissolved was measured.
得られた結果を表1に示す。この結果から、ヒアルロン酸オリゴ糖の存在下でヒアルロン酸を水に溶解させることによって、ヒアルロン酸の溶解に要する時間を大幅に短縮できることが確認された。また、ヒアルロン酸ナトリウムの含有量を、不飽和型ヒアルロン酸オリゴ糖の同量以上にすることで溶解時間を短縮できる傾向が見られた。 The obtained results are shown in Table 1. From this result, it was confirmed that by dissolving hyaluronic acid in water in the presence of hyaluronic acid oligosaccharide, the time required for dissolving hyaluronic acid can be significantly shortened. In addition, it was found that the dissolution time can be shortened by making the content of sodium hyaluronate equal to or more than the same amount of unsaturated hyaluronic acid oligosaccharide.
試験例2:ヒアルロン酸組成物の評価
表2及び3に示す組成のヒアルロン酸組成物を調製した。具体的には、室温の水に、他の含有成分を同時に所定量添加し、室温でプロペラ攪拌機にて500rpmの速度で撹拌することにより、ヒアルロン酸を完全に溶解させたヒアルロン酸組成物を製造した。ヒアルロン酸組成物の製造において、ヒアルロン酸の溶解性を以下の方法で評価した。
ヒアルロン酸の溶解性
撹拌開始からヒアルロン酸のダマがなくなり、ヒアルロン酸が完全に溶解するまでの時間(溶解時間)を計測し、以下の判定基準に従って、ヒアルロン酸の溶解性を評価した。
<ヒアルロン酸の溶解性の判定基準>
○:溶解時間が50分未満である。
×:溶解時間が50分以上である。
Test Example 2: Evaluation of hyaluronic acid composition Hyaluronic acid compositions having the compositions shown in Tables 2 and 3 were prepared. Specifically, a hyaluronic acid composition in which hyaluronic acid is completely dissolved is manufactured by adding a predetermined amount of other components simultaneously to water at room temperature and stirring at a speed of 500 rpm with a propeller stirrer at room temperature. did. In the production of the hyaluronic acid composition, the solubility of hyaluronic acid was evaluated by the following method.
Hyaluronic acid solubility Stirring of hyaluronic acid from the start of stirring until hyaluronic acid was completely dissolved and hyaluronic acid was completely dissolved (dissolution time) was measured, and the solubility of hyaluronic acid was evaluated according to the following criteria.
<Criteria for solubility of hyaluronic acid>
○: Dissolution time is less than 50 minutes.
X: Dissolution time is 50 minutes or more.
また、評価モニター10名によって、各ヒアルロン酸組成物約0.5を顔に塗布し、塗布時の使用感(伸ばし易さ、塗布感、べたつき感のなさ)及び塗布後の使用感(保湿感)について評価した。評価は、以下に示す基準で1点〜10点の間で評点化したVisual Analogue Scale(以下、VASと記載する)によるアンケートを実施することにより行った。アンケート結果を平均し、小数点第一位を四捨五入することにより、評価結果をまとめた。
<伸ばし易さ>
1点:塗布時に伸ばし難い
10点:塗布時に伸ばし易い
<塗布感>
1点:塗布時に重厚な塗布感がない
10点:塗布時に重厚な塗布感がある
<べたつき感のなさ>
1点:塗布時にべたつく
10点:塗布時にべたつかない
<保湿感>
1点:塗布から15秒後にしっとりとした感じがない
10点:塗布から15秒後にしっとりとした感じがある
In addition, each evaluation hyaluronic acid composition of about 0.5 is applied to the face by 10 evaluation monitors, and the feeling of use (the ease of stretching, the feeling of applying, the feeling of stickiness not feeling) and the feeling of using after application (moisturizing feeling) ) Was evaluated. The evaluation was conducted by conducting a questionnaire based on Visual Analogue Scale (hereinafter referred to as VAS) which is scored between 1 and 10 based on the criteria shown below. The questionnaire results were averaged, and the evaluation results were summarized by rounding off the first decimal place.
<Ease of extension>
1 point: Difficult to extend at the time of application 10 points: Easy to extend at the time of application <Applying feeling>
1 point: There is no heavy application feeling at the time of application 10 points: There is a heavy application feeling at the time of application <no stickiness>
1 point: Sticky during application 10 points: Not sticky during application <Moisturizing feeling>
1 point: 15 seconds after application no feeling of moistness 10 points: 15 seconds after application feeling of moist
得られた結果を表2及び3に示す。ヒアルロン酸を単独で0.05重量%以上含む場合(比較例1及び2)では、良好な塗布感及び保湿感が認められたものの、ヒアルロン酸の溶解性が悪く、更に塗布時に伸ばし難く、しかもべたつきが感じられ、十分な使用感が得られなかった。また、ヒアルロン酸が0.05重量%未満の場合(比較例3及び4)では、ヒアルロン酸の溶解性は良好であったものの、ヒアルロン酸オリゴ糖の有無にかかわらず、塗布感及び保湿感が不十分になっていた。更に、ヒアルロン酸0.5重量%以上と共に、低分子化ヒアルロン酸、N−アセチルD−グルコサミン、又はラクトースを含む場合でも、ヒアルロン酸の溶解性が悪く、更に塗布時の伸ばし易さ及びべたつきの点でも改善は認められなかった。 The obtained results are shown in Tables 2 and 3. In the case of containing 0.05% by weight or more of hyaluronic acid alone (Comparative Examples 1 and 2), although good coating feeling and moisturizing feeling were observed, the solubility of hyaluronic acid is poor, and further, it is difficult to stretch at the time of application I felt stickiness and I did not get a sufficient feeling of use. Moreover, when hyaluronic acid was less than 0.05% by weight (Comparative Examples 3 and 4), although the solubility of hyaluronic acid was good, the feeling of application and moisturizing were maintained regardless of the presence or absence of hyaluronic acid oligosaccharides. It was insufficient. Furthermore, even when containing low molecular weight hyaluronic acid, N-acetyl D-glucosamine, or lactose together with 0.5 wt% or more of hyaluronic acid, the solubility of hyaluronic acid is poor, and further, the ease of application and stickiness There was no improvement in point either.
これに対して、ヒアルロン酸0.05重量%以上と共に、ヒアルロン酸オリゴ糖を含む場合(実施例6〜18)では、ヒアルロン酸の溶解性が良好であり、しかも、塗布時の伸ばし易さ、塗布感、べたつき感のなさ、及び保湿感の全ての点で良好であった。特に、ヒアルロン酸オリゴ糖として、不飽和型ヒアルロン酸オリゴ糖を使用した場合(実施例8〜18)には、塗布時の伸ばし易さ及びべたつき感のなさがより一層向上していた。 On the other hand, when hyaluronic acid oligosaccharides are contained together with 0.05% by weight or more of hyaluronic acid (Examples 6 to 18), the solubility of hyaluronic acid is good, and it is easy to extend during application. It was good in all points of the application feeling, the non-stickiness and the moisturizing feeling. In particular, when unsaturated hyaluronic acid oligosaccharide was used as the hyaluronic acid oligosaccharide (Examples 8 to 18), the ease of coating and the absence of stickiness were further improved.
試験例3:ヒアルロン酸を含む化粧水の評価
表4に示す組成の化粧水を調製した。具体的には、先ず、表4の(I)に示す成分を所定量混合し、混合液(I)を調製した。また、表4の(II)に示す成分を所定量混合し、混合液(II)を調製した。次いで、混合液(II)に混合液(I)を加えて撹拌することにより、化粧水(ヒアルロン酸最終濃度0.05重量%)を製造した。
Test Example 3: Evaluation of lotion containing hyaluronic acid A lotion having the composition shown in Table 4 was prepared. Specifically, first, a predetermined amount of the components shown in Table 4 (I) was mixed to prepare a mixed solution (I). A predetermined amount of the components shown in (II) of Table 4 was mixed to prepare a mixed solution (II). Next, the liquid mixture (I) was added to the liquid mixture (II) and stirred to prepare a lotion (hyaluronic acid final concentration 0.05% by weight).
得られた化粧水について、前記試験例1と同様の方法で、塗布時の使用感(伸ばし易さ、塗布感、べたつき感のなさ)及び塗布後の使用感(保湿感)について評価した。 The obtained lotion was evaluated in the same manner as in Test Example 1 with respect to the feeling during use (ease of stretching, feeling of application, no stickiness) and feeling after use (moisturizing feeling).
得られた結果を表4に示す。この結果から、ヒアルロン酸0.05重量%を含み、ヒアルロン酸オリゴ糖を含まない化粧水(比較例10及び11)では、塗布時に伸ばし難く、べたつきも感じられ、使用感が満足できるものではなかった。これに対して、ヒアルロン酸0.05重量%と共に、ヒアルロン酸オリゴ糖を含む化粧水(実施例19及び20)では、塗布時の伸ばし易さ、塗布感、べたつき感のなさ、及び保湿感の全ての点で良好であった。 The obtained results are shown in Table 4. From this result, it is difficult to stretch at the time of application, and the stickiness is felt, and the feeling of use is not satisfactory in the lotion (Comparative Examples 10 and 11) containing 0.05% by weight of hyaluronic acid and containing no hyaluronic acid oligosaccharide It was. On the other hand, in the lotion containing hyaluronic acid 0.05% by weight and hyaluronic acid oligosaccharides (Examples 19 and 20), it is easy to stretch at the time of application, a feeling of application, no stickiness, and a moisturizing feeling. Good in all respects.
処方例1〜20
表5及び表6に示す組成の化粧水を調製した。具体的には、先ず、表5及び6の(A)に示す成分を所定量混合し、混合液(A)を調製した。また、別途、表5及び6の(B)に示す成分を所定量混合し、混合液(B)を調製した。次いで、混合液(B)に混合液(A)を加えて撹拌することにより、化粧水を製造した。得られた化粧水は、いずれも、塗布時の伸ばし易さ、塗布感、べたつき感のなさ、及び保湿感の全ての点で良好であった。
Formulation Examples 1-20
Lotions having the compositions shown in Table 5 and Table 6 were prepared. Specifically, first, a predetermined amount of the components shown in Tables 5 and 6 (A) was mixed to prepare a mixed solution (A). Separately, a predetermined amount of the components shown in Tables 5 and 6 (B) was mixed to prepare a mixed solution (B). Next, the liquid mixture (A) was added to the liquid mixture (B) and stirred to produce a lotion. All the obtained lotions were good in all points of the ease of application at the time of application, a feeling of application, no stickiness, and a feeling of moisture.
なお、これらの処方例において、ヒアルロン酸ナトリウムは、商品名「ヒアルロンサン HA−LQH」(平均分子量120〜220万;キユーピー株式会社)を使用し、低分子ヒアルロン酸は、商品名「ヒアルロン酸FCH−SU」(分子量5〜11万)(キッコーマンバイオケミファ株式会社製)を使用した。また、これらの処方例において、各飽和型のヒアルロン酸オリゴ糖はいずれも市販品を使用した。更に、これらの処方例において、各不飽和型のヒアルロン酸オリゴ糖は、非還元末端に位置するグルクロン酸の4位の炭素原子に結合している水酸基が除去され、4位の炭素原子と5位の炭素原子が二重結合で結合している構造を有しているものであり、いずれも市販品を使用した。 In these formulation examples, sodium hyaluronate uses the trade name "Hyaluronic acid HA-LQH" (average molecular weight 120 to 220,000; Kewpie Corporation), and low molecular weight hyaluronic acid has the trade name "Hyaluronic acid FCH- SU (with a molecular weight of 5 to 110,000) (manufactured by Kikkoman Biochemifa Co., Ltd.) was used. Moreover, in these formulation examples, each saturation type hyaluronic acid oligosaccharide used any commercial item. Furthermore, in these formulation examples, each unsaturated type hyaluronic acid oligosaccharide has a hydroxyl group bonded to the 4-position carbon atom of glucuronic acid located at the non-reducing end removed, and the 4-position carbon atom and 5 The carbon atoms at the positions have a structure in which they are bonded by a double bond, and commercial products were used for all of them.
Claims (5)
(B) Dissolution of hyaluronic acid and / or a salt thereof, characterized in that (A) hyaluronic acid and / or a salt thereof are dissolved in water in the presence of unsaturated hyaluronic acid oligosaccharide and / or a salt thereof How to save time.
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