JP2011241188A - Epidermal keratinization-normalizing agent, external preparation for skin containing the epidermal keratinization-normalizing agent, external preparation for normalizing epidermis, cosmetic, cosmetic for normalizing epidermis, unregulated drug and unregulated drug for normalizing epidermis - Google Patents
Epidermal keratinization-normalizing agent, external preparation for skin containing the epidermal keratinization-normalizing agent, external preparation for normalizing epidermis, cosmetic, cosmetic for normalizing epidermis, unregulated drug and unregulated drug for normalizing epidermis Download PDFInfo
- Publication number
- JP2011241188A JP2011241188A JP2010115637A JP2010115637A JP2011241188A JP 2011241188 A JP2011241188 A JP 2011241188A JP 2010115637 A JP2010115637 A JP 2010115637A JP 2010115637 A JP2010115637 A JP 2010115637A JP 2011241188 A JP2011241188 A JP 2011241188A
- Authority
- JP
- Japan
- Prior art keywords
- normalizing
- keratinization
- epidermis
- skin
- polyglutamic acid
- 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.)
- Pending
Links
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 87
- 210000003491 skin Anatomy 0.000 title claims abstract description 68
- 210000002615 epidermis Anatomy 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 239000002537 cosmetic Substances 0.000 title claims description 32
- 239000003814 drug Substances 0.000 title claims description 17
- 229940079593 drug Drugs 0.000 title claims description 16
- 230000003780 keratinization Effects 0.000 claims abstract description 101
- 229920002643 polyglutamic acid Polymers 0.000 claims abstract description 89
- 108010020346 Polyglutamic Acid Proteins 0.000 claims abstract description 87
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- 230000007062 hydrolysis Effects 0.000 claims abstract description 8
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 15
- 244000005700 microbiome Species 0.000 claims description 14
- 244000063299 Bacillus subtilis Species 0.000 claims description 11
- 235000014469 Bacillus subtilis Nutrition 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 8
- 108010083364 chungkookjang Proteins 0.000 claims description 6
- 230000003301 hydrolyzing effect Effects 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 6
- 238000010606 normalization Methods 0.000 claims description 5
- 238000011156 evaluation Methods 0.000 description 33
- 108090000623 proteins and genes Proteins 0.000 description 22
- 238000000034 method Methods 0.000 description 21
- 101710088660 Filaggrin Proteins 0.000 description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
- 230000003796 beauty Effects 0.000 description 18
- 239000000686 essence Substances 0.000 description 18
- 239000000839 emulsion Substances 0.000 description 17
- 239000006210 lotion Substances 0.000 description 17
- 210000000434 stratum corneum Anatomy 0.000 description 17
- 102100028314 Filaggrin Human genes 0.000 description 16
- 108010033564 involucrin Proteins 0.000 description 16
- 239000007921 spray Substances 0.000 description 16
- 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 16
- 206010013786 Dry skin Diseases 0.000 description 15
- 230000037336 dry skin Effects 0.000 description 15
- 102000007236 involucrin Human genes 0.000 description 15
- 239000011148 porous material Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 102100031784 Loricrin Human genes 0.000 description 13
- -1 jojoba oil Substances 0.000 description 13
- 108010079309 loricrin Proteins 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 108010058734 transglutaminase 1 Proteins 0.000 description 13
- 229920001661 Chitosan Polymers 0.000 description 12
- 206010012438 Dermatitis atopic Diseases 0.000 description 12
- 102100030944 Protein-glutamine gamma-glutamyltransferase K Human genes 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 201000008937 atopic dermatitis Diseases 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 210000002510 keratinocyte Anatomy 0.000 description 10
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 235000011187 glycerol Nutrition 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 230000001737 promoting effect Effects 0.000 description 9
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 8
- 229960002989 glutamic acid Drugs 0.000 description 8
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 8
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- 229950011392 sorbitan stearate Drugs 0.000 description 8
- 229940032094 squalane Drugs 0.000 description 8
- 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 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 7
- 235000013922 glutamic acid Nutrition 0.000 description 7
- 239000004220 glutamic acid Substances 0.000 description 7
- 229920002674 hyaluronan Polymers 0.000 description 7
- 229960003160 hyaluronic acid Drugs 0.000 description 7
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 238000012258 culturing Methods 0.000 description 6
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 6
- 238000005227 gel permeation chromatography Methods 0.000 description 6
- 230000001603 reducing effect Effects 0.000 description 6
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 5
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000007872 degassing Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 229940057995 liquid paraffin Drugs 0.000 description 4
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 4
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 4
- 229960002216 methylparaben Drugs 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 239000012695 Ce precursor Substances 0.000 description 3
- 229920002101 Chitin Polymers 0.000 description 3
- 108010076876 Keratins Proteins 0.000 description 3
- 102000011782 Keratins Human genes 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 3
- 229960000541 cetyl alcohol Drugs 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 229960000735 docosanol Drugs 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000003020 moisturizing effect Effects 0.000 description 3
- 239000010802 sludge Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- CWSZBVAUYPTXTG-UHFFFAOYSA-N 5-[6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxy-5-[4-hydroxy-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OCCO)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 CWSZBVAUYPTXTG-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 101150116870 LORICRIN gene Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- MIUIRGGKIICMBP-NFOZDHADSA-N [27-oxo-27-[[(2s,3s,4r)-1,3,4-trihydroxyoctadecan-2-yl]amino]heptacosyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)[C@H](O)CCCCCCCCCCCCCC MIUIRGGKIICMBP-NFOZDHADSA-N 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229940048864 ceramide 1 Drugs 0.000 description 2
- 230000007073 chemical hydrolysis Effects 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 239000008406 cosmetic ingredient Substances 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 239000002781 deodorant agent Substances 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 210000000245 forearm Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000006456 gs medium Substances 0.000 description 2
- 239000003676 hair preparation Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 230000037394 skin elasticity Effects 0.000 description 2
- 230000037393 skin firmness Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 229920003169 water-soluble polymer Polymers 0.000 description 2
- 239000010497 wheat germ oil Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BJDAUCLANVMIOB-UHFFFAOYSA-N (3-decanoyloxy-2,2-dimethylpropyl) decanoate Chemical compound CCCCCCCCCC(=O)OCC(C)(C)COC(=O)CCCCCCCCC BJDAUCLANVMIOB-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- WAYINTBTZWQNSN-UHFFFAOYSA-N 11-methyldodecyl 3,5,5-trimethylhexanoate Chemical compound CC(C)CCCCCCCCCCOC(=O)CC(C)CC(C)(C)C WAYINTBTZWQNSN-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- VRBHTEGUHVNKEA-UHFFFAOYSA-N 16-methylheptadecyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC(C)C VRBHTEGUHVNKEA-UHFFFAOYSA-N 0.000 description 1
- FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 description 1
- NCLNAHJFXIKYBY-UHFFFAOYSA-N 2-hexyldecyl 16-methylheptadecanoate Chemical compound CCCCCCCCC(CCCCCC)COC(=O)CCCCCCCCCCCCCCC(C)C NCLNAHJFXIKYBY-UHFFFAOYSA-N 0.000 description 1
- JEMDXOYRWHZUCG-UHFFFAOYSA-N 2-octadecanoyloxypropyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCCCCCCCCCCC JEMDXOYRWHZUCG-UHFFFAOYSA-N 0.000 description 1
- UIVPNOBLHXUKDX-UHFFFAOYSA-N 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate Chemical compound CC(C)(C)CC(C)CCOC(=O)CC(C)CC(C)(C)C UIVPNOBLHXUKDX-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-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
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- 102100026112 60S acidic ribosomal protein P2 Human genes 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002567 Chondroitin Polymers 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 235000017788 Cydonia oblonga Nutrition 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108700041153 Filaggrin Proteins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000691878 Homo sapiens 60S acidic ribosomal protein P2 Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- GWFGDXZQZYMSMJ-UHFFFAOYSA-N Octadecansaeure-heptadecylester Natural products CCCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCCCC GWFGDXZQZYMSMJ-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000005775 Parakeratosis Diseases 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 235000019774 Rice Bran oil Nutrition 0.000 description 1
- 238000010818 SYBR green PCR Master Mix Methods 0.000 description 1
- 239000004902 Softening Agent Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 206010048218 Xeroderma Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- GORMSINSWZJIKL-UHFFFAOYSA-N [3-(2-ethylhexanoyloxy)-2,2-dimethylpropyl] 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OCC(C)(C)COC(=O)C(CC)CCCC GORMSINSWZJIKL-UHFFFAOYSA-N 0.000 description 1
- CMPDPBDUZTUXAD-UHFFFAOYSA-N [3-hydroxy-2-(16-methylheptadecanoyloxy)propyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCC(C)C CMPDPBDUZTUXAD-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 229940069521 aloe extract Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000003212 astringent agent Substances 0.000 description 1
- 201000002463 atopic dermatitis 2 Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229920003064 carboxyethyl cellulose Polymers 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 229940074979 cetyl palmitate Drugs 0.000 description 1
- 239000010628 chamomile oil Substances 0.000 description 1
- 235000019480 chamomile oil Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- XAKXZZPEUKNHMA-UHFFFAOYSA-N decyl decanoate Chemical compound CCCCCCCCCCOC(=O)CCCCCCCCC XAKXZZPEUKNHMA-UHFFFAOYSA-N 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 235000008524 evening primrose extract Nutrition 0.000 description 1
- 239000010475 evening primrose oil Substances 0.000 description 1
- 229940089020 evening primrose oil Drugs 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000010643 fennel seed oil Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008169 grapeseed oil Substances 0.000 description 1
- PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 1
- XJNUECKWDBNFJV-UHFFFAOYSA-N hexadecyl 2-ethylhexanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)C(CC)CCCC XJNUECKWDBNFJV-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 206010021198 ichthyosis Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229940100554 isononyl isononanoate Drugs 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- 108010075526 keratohyalin Proteins 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- NKBWPOSQERPBFI-UHFFFAOYSA-N octadecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCCCC NKBWPOSQERPBFI-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- 239000010702 perfluoropolyether Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 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
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- BALXUFOVQVENIU-KXNXZCPBSA-N pseudoephedrine hydrochloride Chemical compound [H+].[Cl-].CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-KXNXZCPBSA-N 0.000 description 1
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 1
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 1
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 1
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 1
- DQAKJEWZWDQURW-UHFFFAOYSA-N pyrrolidonecarboxylic acid Chemical class OC(=O)N1CCCC1=O DQAKJEWZWDQURW-UHFFFAOYSA-N 0.000 description 1
- 229940079889 pyrrolidonecarboxylic acid Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 229940108325 retinyl palmitate Drugs 0.000 description 1
- 235000019172 retinyl palmitate Nutrition 0.000 description 1
- 239000011769 retinyl palmitate Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000008165 rice bran oil Substances 0.000 description 1
- 239000010668 rosemary oil Substances 0.000 description 1
- 229940058206 rosemary oil Drugs 0.000 description 1
- 101150038541 rplP2 gene Proteins 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 150000003377 silicon compounds Chemical class 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000005808 skin problem Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- QPQANCNBWQXGTQ-UHFFFAOYSA-N trihydroxy(trimethylsilylperoxy)silane Chemical compound C[Si](C)(C)OO[Si](O)(O)O QPQANCNBWQXGTQ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
Landscapes
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
本発明は、表皮角化正常化剤及び該表皮角化正常化剤を含む皮膚外用剤、表皮正常化用外用剤、化粧料、表皮正常化用化粧料、医薬部外品、又は表皮正常化用医薬部外品に関する。具体的には、例えば、皮膚における表皮の角化を正常化することにより、乾燥肌、毛穴の目立ち、肌荒れ又はアトピー性皮膚炎等を軽減し得る表皮角化正常化剤、及び、該表皮角化正常化剤を含む皮膚外用剤、表皮正常化用外用剤、化粧料、表皮正常化用化粧料、医薬部外品、又は表皮正常化用医薬部外品に関する。 The present invention relates to an epidermal keratinization normalizing agent and a skin external preparation containing the epidermal keratinization normalizing agent, an external preparation for normalizing the epidermis, a cosmetic, a cosmetic for normalizing the epidermis, a quasi drug, or a normalization of the epidermis. Quasi-drugs. Specifically, for example, by normalizing the keratinization of the epidermis in the skin, dry skin, conspicuous pores, rough skin or atopic dermatitis and the like normalizing agent for keratinization of the epidermis, and the epidermal horn The present invention relates to an external preparation for skin, an external preparation for normalizing epidermis, a cosmetic, a cosmetic for normalizing epidermis, a quasi drug, or a quasi drug for normalizing epidermis.
皮膚の外方側にある表皮は、生体を防御したり、水分の過剰な蒸発を防いだりするバリア機能を有しており、最も内方側にある基底層と、該基底層から外方側へ向かって順に配置されている有棘層と顆粒層と角質層との４層で構成されている。また、表皮を構成する各層の細胞の大半は、基底層で生じた角化細胞に由来するものであり、該角化細胞は、基底層から外方側へ角化過程を経ながら押し出され、最外層の角質層を形成する角質細胞になる。
角質細胞は、ケラチン繊維とケラチン繊維の周囲にあるコーニファイドエンベロープ（以下、ＣＥともいう）などとによって形成されている。そして、ＣＥは、角化細胞の角化に伴い産生される、フィラグリン、インボルクリン、ロリクリン等の複数のＣＥ前駆体蛋白質が、トランスグルタミナーゼ−１などの酵素により架橋され不溶化することにより形成される。
また、角質細胞は、最終的には角質層から剥がれ落ちるが、一方で、表皮におけるバリア機能を維持するため、角化細胞が基底層で生じ角質層に至って角質細胞になって剥がれ落ちるという代謝のサイクルが、１サイクル約４週間をかけて繰り返されている。
The epidermis on the outer side of the skin has a barrier function of protecting the living body and preventing excessive evaporation of water, and is the innermost basal layer and the outer side from the basal layer. It is composed of four layers, the spinous layer, the granular layer, and the stratum corneum, which are sequentially arranged toward each other. Further, most of the cells of each layer constituting the epidermis are derived from keratinocytes generated in the basal layer, and the keratinocytes are extruded from the basal layer to the outside while undergoing a keratinization process, It becomes keratinocytes forming the outermost horny layer.
Keratinocytes are formed by keratin fibers and a cornified envelope (hereinafter also referred to as CE) around the keratin fibers. Then, CE is formed by insolubilizing a plurality of CE precursor proteins such as filaggrin, involucrin, and loricrin produced by keratinocyte keratinization by cross-linking with an enzyme such as transglutaminase-1.
In addition, keratinocytes eventually peel off from the stratum corneum, but on the other hand, in order to maintain the barrier function in the epidermis, keratinocytes occur in the basal layer and reach the stratum corneum to become stratum corneum cells and then peel off. The cycle is repeated for about 4 weeks per cycle.
しかしながら、加齢、不規則な生活、又はストレスなどにより斯かる代謝のサイクルが正常に繰り返されなくなると、角化亢進や不全角化が起こり、乾燥肌、毛穴の目立ち、又は肌荒れなどの皮膚トラブルが発生し得る。 However, when such metabolic cycles are not normally repeated due to aging, irregular life, stress, etc., hyperkeratosis and parakeratosis occur, resulting in skin problems such as dry skin, conspicuous pores, or rough skin. Can occur.
従来、このような皮膚トラブルに対して、代謝のサイクルを整え表皮の角化を正常化し得る表皮角化正常化剤としては、様々なものが知られており、例えば、角化過程に関与している上記のごときＣＥ前駆体蛋白質の産生を促進するものが知られている。 Conventionally, with respect to such skin troubles, various agents are known as epidermal keratinization normalizing agents capable of normalizing the keratinization of the epidermis by adjusting the metabolic cycle and, for example, are involved in the keratinization process. Those which promote the production of CE precursor protein as described above are known.
この種の表皮角化正常化剤としては、具体的には、例えば、セイロンテツボクの種子抽出物を含み、インボルクリンの産生を促進することにより正常な角化を促し代謝のサイクルを整え得るものが提案されている（特許文献１）。 Specific examples of the epidermal keratinization normalizing agent of this type include, for example, Ceylon tetsuboku seed extract, which can promote normal keratinization by promoting the production of involucrin and regulate the metabolic cycle. Has been proposed (Patent Document 1).
しかしながら、斯かる表皮角化正常化剤は、インボルクリンの産生促進能が必ずしも十分なものではない。また、トランスグルタミナーゼ−１などの酵素蛋白質、フィラグリンやロリクリン等のＣＥ前駆体蛋白質の産生能に優れるものでもない。従って、斯かる表皮角化正常化剤は、角化に関わる蛋白質の産生能に必ずしも優れるものではなく、表皮の角化を正常化する性能が十分なものではないという問題がある。 However, such an epidermal keratinization normalizing agent does not always have a sufficient ability to promote involucrin production. Nor is it excellent in the ability to produce enzyme proteins such as transglutaminase-1 and CE precursor proteins such as filaggrin and loricrin. Therefore, such an epidermal keratinization normalizing agent is not necessarily excellent in the ability to produce a protein involved in keratinization, and there is a problem that the ability to normalize keratinization of the epidermis is not sufficient.
本発明は、上記の問題点等に鑑み、表皮の角化を正常化し得る表皮角化正常化剤を提供することを課題とする。また、該表皮角化正常化剤を含む皮膚外用剤、表皮正常化用外用剤、化粧料、表皮正常化用化粧料、医薬部外品、又は表皮正常化用医薬部外品を提供することを課題とする。 In view of the above problems and the like, an object of the present invention is to provide an epidermal keratinization normalizing agent that can normalize epidermal keratinization. Also, to provide an external preparation for skin, an external preparation for normalizing epidermis, a cosmetic, a cosmetic for normalizing epidermis, a quasi drug, or a quasi drug for normalizing epidermis, which contains the normalizing agent for epidermal keratinization. Is an issue.
本発明に係る表皮角化正常化剤は、ポリグルタミン酸を加水分解処理することにより生じた加水分解ポリグルタミン酸又はその塩を有効成分として含有することを特徴としている。
本発明に係る表皮角化正常化剤は、ポリグルタミン酸を加水分解処理することにより生じた加水分解ポリグルタミン酸又はその塩を有効成分として含有することにより、表皮におけるフィラグリン、インボルクリン、ロリクリン、又はトランスグルタミナーゼ−１をコードする遺伝子の発現を促進し得る。従って、これら蛋白質の産生を促進し、皮膚における表皮の角化を正常化させ得る。
The epidermal keratinization normalizing agent according to the present invention is characterized by containing hydrolyzed polyglutamic acid or a salt thereof produced by hydrolyzing polyglutamic acid as an active ingredient.
The epidermal keratinization normalizing agent according to the present invention contains hydrolyzed polyglutamic acid or a salt thereof produced as a result of hydrolyzing polyglutamic acid as an active ingredient, and thus filaggrin, involucrin, loricrin, or transglutaminase in the epidermis. It can promote the expression of the gene encoding -1. Therefore, it can promote the production of these proteins and normalize the keratinization of the epidermis in the skin.
また、本発明に係る表皮角化正常化剤は、前記ポリグルタミン酸の酸沈殿物を加水分解処理することにより生じた加水分解ポリグルタミン酸又はその塩を有効成分として含有することが好ましい。 The epidermal keratinization normalizing agent according to the present invention preferably contains, as an active ingredient, hydrolyzed polyglutamic acid or a salt thereof produced by subjecting the acid precipitate of polyglutamic acid to hydrolysis treatment.
また、本発明に係る表皮角化正常化剤は、Ｂａｃｉｌｌｕｓ属の微生物が生成する粗ポリグルタミン酸を加水分解処理することにより生じた加水分解ポリグルタミン酸又はその塩を有効成分として含有することが好ましい。
また、前記Ｂａｃｉｌｌｕｓ属の微生物がＢａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ ｖａｒ ｃｈｕｎｇｋｏｏｋｊａｎｇ，ＫＣＴＣ ０６９７ＢＰであることが好ましい。
また、前記加水分解ポリグルタミン酸の平均分子量が４００〜１０万であることが好ましい。
これらの好ましい構成により、表皮の角化がより確実に正常化され得るという利点がある。
Further, the epidermal keratinization normalizing agent according to the present invention preferably contains, as an active ingredient, hydrolyzed polyglutamic acid or a salt thereof produced by hydrolyzing a crude polyglutamic acid produced by a Bacillus genus microorganism.
Moreover, it is preferable that the microorganism of the genus Bacillus is Bacillus subtilis var chungkookjang, KCTC 0697BP.
The average molecular weight of the hydrolyzed polyglutamic acid is preferably 400 to 100,000.
These preferred configurations have the advantage that epidermal keratinization can be more reliably normalized.
本発明に係る皮膚外用剤、表皮正常化用外用剤、化粧料、表皮正常化用化粧料、医薬部外品、又は表皮正常化用医薬部外品は、前記表皮角化正常化剤を含むことを特徴とする。 The external preparation for skin according to the present invention, external preparation for normalizing epidermis, cosmetic, cosmetic for normalizing epidermis, quasi drug, or quasi drug for normalizing epidermis contains the normalizing agent for keratinization of epidermis. It is characterized by
本発明の表皮角化正常化剤は、表皮の角化を正常化し得るという効果を奏する。 The epidermal keratinization normalizing agent of the present invention has the effect of normalizing keratinization of the epidermis.
以下に、本発明の表皮角化正常化剤の実施形態について説明する。
本実施形態の表皮角化正常化剤は、ポリグルタミン酸を加水分解処理することにより生じた加水分解ポリグルタミン酸又はその塩を有効成分として含有するものである。また、本実施形態の表皮角化正常化剤は、前記加水分解ポリグルタミン酸又はその塩以外の成分が含まれ得るものである。
前記ポリグルタミン酸は、通常、グルタミン酸がγ−グルタミル結合で連結してなるγ−ポリグルタミン酸である。また、通常、水溶性であり、分子量が数１０万〜数１００万である。
また、前記ポリグルタミン酸としては、化学合成されたポリグルタミン酸、又は、Ｂａｃｉｌｌｕｓ属などの微生物が生成した粗ポリグルタミン酸等が挙げられ、表皮角化正常化剤が表皮の角化を正常化し得る性能により優れるという点で、Ｂａｃｉｌｌｕｓ属の微生物が生成した粗ポリグルタミン酸が好ましい。また、Ｂａｃｉｌｌｕｓ属の微生物が生成した粗ポリグルタミン酸としては、表皮角化正常化剤が表皮の角化を正常化し得る性能により優れるという点で、Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ ｖａｒ ｃｈｕｎｇｋｏｏｋｊａｎｇが生成した粗ポリグルタミン酸が好ましい。
Hereinafter, an embodiment of the epidermal keratinization normalizing agent of the present invention will be described.
The epidermal keratinization normalizing agent of the present embodiment contains, as an active ingredient, hydrolyzed polyglutamic acid or a salt thereof produced by hydrolyzing polyglutamic acid. In addition, the epidermal keratinization normalizing agent of the present embodiment may contain a component other than the hydrolyzed polyglutamic acid or the salt thereof.
The polyglutamic acid is usually γ-polyglutamic acid in which glutamic acid is linked by γ-glutamyl bond. Further, it is usually water-soluble and has a molecular weight of several hundred thousand to several million.
Examples of the polyglutamic acid include chemically synthesized polyglutamic acid, or crude polyglutamic acid produced by microorganisms such as the genus Bacillus, and the like, and the epidermal keratinization normalizing agent is capable of normalizing keratinization of the epidermis. Crude polyglutamic acid produced by a Bacillus microorganism is preferable because it is excellent. The crude polyglutamic acid produced by a Bacillus genus microorganism is preferably a crude polyglutamic acid produced by Bacillus subtilis var chungkookjang, in that the epidermal keratinization normalizing agent is superior in its ability to normalize epidermal keratinization.
前記Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ ｖａｒ ｃｈｕｎｇｋｏｏｋｊａｎｇは、詳しくは、枯草菌（Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ）の１種であるＢａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ ｖａｒ ｃｈｕｎｇｋｏｏｋｊａｎｇ（バチルス サブティリス チョングッチャン），ＫＣＴＣ ０６９７ＢＰ菌株である。なお、この菌株は、生命工学研究所遺伝子銀行（ＫＣＴＣ，大韓民国大田広域市儒域区魚隠洞５２所在）に寄託されたものである。 More specifically, the Bacillus subtilis var chungkookjang is Bacillus subtilis var chungkookjang (bacillus subtilis jungbukchan 6), which is one of Bacillus subtilis 6. KCTCP. The strain was deposited at the Institute of Biotechnology, Gene Bank (KCTC, 52, Uogakudo Cave, Yusang-gu, Daejeon, South Korea).
なお、前記Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ ｖａｒ ｃｈｕｎｇｋｏｏｋｊａｎｇは、チョングッチャン（清麹醤）から分離されたものに由来する。また、該菌株は、耐塩性を有し、胞子を形成しにくく、通常、菌株自体がプラスミドを含有していない。 In addition, the said Bacillus subtilis var chungkookjang originates from what was isolate|separated from Chunggukchan (Kyo-Koji soy). Further, the strain is salt-tolerant, hardly forms spores, and usually the strain itself does not contain a plasmid.
前記ポリグルタミン酸は、Ｄ体又はＬ体のグルタミン酸で構成されているものである。
前記ポリグルタミン酸としては、例えば、Ｌ体グルタミン酸及びＤ体グルタミン酸の両方で構成された混合型ポリグルタミン酸、Ｌ体のグルタミン酸のみで構成されたＬ体ポリグルタミン酸、Ｄ体のグルタミン酸のみで構成されたＤ体ポリグルタミン酸等が挙げられる。なかでも、表皮の角化の正常化性能がより優れたものになり得るというという点で、混合型ポリグルタミン酸が好ましい。なお、前記ポリグルタミン酸は、ラセミ体のものであってもよい。
The polyglutamic acid is composed of D-form or L-form glutamic acid.
Examples of the polyglutamic acid include mixed polyglutamic acid composed of both L-form glutamic acid and D-form glutamic acid, L-form polyglutamic acid composed only of L-form glutamic acid, and D composed of only D-form glutamic acid. Examples include body polyglutamic acid and the like. Among them, mixed polyglutamic acid is preferable in that the normalization performance of keratinization of the epidermis can be more excellent. The polyglutamic acid may be racemic.
Ｂａｃｉｌｌｕｓ属の微生物が生成した粗ポリグルタミン酸は、通常、混合型ポリグルタミン酸である。即ち、Ｂａｃｉｌｌｕｓ属の微生物が生成した粗ポリグルタミン酸は、Ｄ体及びＬ体の両方で構成され得るものであり、Ｂａｃｉｌｌｕｓ属の微生物の種類によってその構成比率及び配列パターンは異なる。また、Ｂａｃｉｌｌｕｓ属の枯草菌（Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ）によって生成される粗ポリグルタミン酸は、菌種によってその構成比率及び配列パターンは異なり得る。 The crude polyglutamic acid produced by a Bacillus microorganism is usually a mixed polyglutamic acid. That is, the crude polyglutamic acid produced by the Bacillus genus microorganism can be composed of both D- and L-forms, and the composition ratio and the sequence pattern differ depending on the type of the Bacillus genus microorganism. Further, the crude polyglutamic acid produced by Bacillus subtilis of the genus Bacillus may have different composition ratios and sequence patterns depending on the bacterial species.
前記粗ポリグルタミン酸は、例えば、Ｂａｃｉｌｌｕｓ属の微生物を培養することにより得ることができる。Ｂａｃｉｌｌｕｓ属の微生物の培養方法としては、ポリグルタミン酸が生成されるものであれば特に限定されるものではなく、具体的には、例えば、グルタミン酸の存在下でＧＳ培地等において、３０〜５５℃で、適宜適当な時間培養する方法が挙げられる。なお、培地は、寒天などの固体状であっても、液体状であってもよい。 The crude polyglutamic acid can be obtained, for example, by culturing a microorganism of the genus Bacillus. The method for culturing a microorganism of the genus Bacillus is not particularly limited as long as polyglutamic acid is produced, and specifically, for example, in the presence of glutamic acid in a GS medium or the like, at 30 to 55° C. And a method of culturing for an appropriate time. The medium may be solid such as agar or liquid.
前記加水分解処理は、前記粗ポリグルタミン酸などのポリグルタミン酸をより低分子のものにするために行うものである。前記加水分解処理の方法としては、塩酸などの無機酸若しくは有機酸等の存在下で行う化学的な加水分解処理方法、又は、γ−ポリグルタミン酸分解酵素による酵素的な加水分解処理方法などが挙げられる。なかでも、比較的簡便に行えるという点で、無機酸の存在下で行う化学的な加水分解処理方法が好ましい。 The hydrolysis treatment is performed in order to make the polyglutamic acid such as the crude polyglutamic acid have a lower molecular weight. Examples of the hydrolysis treatment method include a chemical hydrolysis treatment method performed in the presence of an inorganic acid such as hydrochloric acid or an organic acid, or an enzymatic hydrolysis treatment method with γ-polyglutamic acid degrading enzyme. Be done. Among them, a chemical hydrolysis treatment method performed in the presence of an inorganic acid is preferable because it can be performed relatively easily.
前記加水分解ポリグルタミン酸は、塩の状態であってもよく、斯かる塩としては、例えば、カリウム、ナトリウム、カルシウム、マグネシウム、アルミニウム、亜鉛等の無機金属塩、又はアンモニウム塩などが挙げられる。 The hydrolyzed polyglutamic acid may be in the form of a salt, and examples of such a salt include inorganic metal salts such as potassium, sodium, calcium, magnesium, aluminum and zinc, and ammonium salts.
前記加水分解ポリグルタミン酸又はその塩としては、表皮の角化の正常化性能がより優れたものになり得るというという点で、Ｂａｃｉｌｌｕｓ属の微生物によって生成された粗ポリグルタミン酸を加水分解処理することにより生じたものが好ましい。 As the hydrolyzed polyglutamic acid or a salt thereof, by hydrolyzing the crude polyglutamic acid produced by a Bacillus microorganism in that the normalization performance of keratinization of the epidermis can be more excellent. What has occurred is preferred.
前記加水分解ポリグルタミン酸は、分子量が特に限定されるものではないが、表皮の角化の正常化性能がより優れたものになり得るという点で、平均分子量が４００〜１０万であることが好ましく、８００〜１００００であることがより好ましく、１０００〜２０００であることがさらに好ましい。
前記平均分子量は、ゲル浸透クロマトグラフィー（ＧＰＣ）によって求めたものであり、詳しくは、後述する実施例に記載された方法によって測定されたものである。
The hydrolyzed polyglutamic acid is not particularly limited in molecular weight, but the average molecular weight is preferably 400 to 100,000 in that the normalization performance of keratinization of the epidermis can be more excellent. , 800 to 10,000, more preferably 1,000 to 2,000.
The average molecular weight is determined by gel permeation chromatography (GPC), and more specifically, it is measured by the method described in Examples below.
前記加水分解ポリグルタミン酸又はその塩は、前記表皮角化正常化剤における含有率が、特に限定されるものではない。加水分解ポリグルタミン酸が溶媒に溶解することにより表皮角化正常化剤が溶液状になっている場合などにおいては、凍結乾燥法などにより溶媒を除去したあとの固形物量を測定することにより、表皮角化正常化剤における加水分解ポリグルタミン酸又はその塩の含有率が求められる。なお、表皮角化正常化剤が溶液状であっても、加水分解ポリグルタミン酸又はその塩のみからなる固形状であっても、該溶液状のもの又は固形状のものを表皮角化正常化剤として用いることができる。 The content of the hydrolyzed polyglutamic acid or its salt in the skin keratinization normalizing agent is not particularly limited. When the hydrolyzed polyglutamic acid is dissolved in a solvent and the epidermal keratinization normalizing agent is in the form of a solution, by measuring the solid content after removing the solvent by a freeze-drying method, the epidermal horn The content of hydrolyzed polyglutamic acid or a salt thereof in the normalizing agent is determined. In addition, even if the epidermal keratinization normalizing agent is in a solution form, even if it is in a solid form consisting only of hydrolyzed polyglutamic acid or a salt thereof, the solution form or the solid form is a skin keratinization normalizing agent. Can be used as
前記表皮角化正常化剤は、前記加水分解ポリグルタミン酸又はその塩を含むことから、フィラグリン、インボルクリン、ロリクリン、又は酵素としてのトランスグルタミナーゼ−１といった角化に関わる各蛋白質をコードするｍＲＮＡの発現を促進し得る。そして、これら各蛋白質をコードするｍＲＮＡの発現が促進されることにより、フィラグリン、インボルクリン、ロリクリン、又はトランスグルタミナーゼ−１の産生が促進され得る。その結果、皮膚における表皮の角化が正常化され得る。 The epidermal keratinization normalizing agent, since it contains the hydrolyzed polyglutamic acid or a salt thereof, expression of mRNA encoding each protein involved in keratinization such as filaggrin, involucrin, loricrin, or transglutaminase-1 as an enzyme. Can be promoted. Then, by promoting the expression of mRNA encoding each of these proteins, the production of filaggrin, involucrin, loricrin, or transglutaminase-1 can be promoted. As a result, keratinization of the epidermis in the skin can be normalized.
例えば、前記フィラグリンは、角質層の内方側にある顆粒層に存在するケラトヒアリン顆粒に含まれるタンパク質であり、プロフィラグリンから合成される。合成されたフィラグリンは、角化細胞の角化に伴い、角質層下層ではケラチン繊維同士をつなぎとめる役割を担い、角質層上層ではアミノ酸等へと加水分解されるものであることが知られている。即ち、フィラグリンは、角質層下層では表皮の皮膚粘弾性を保ち、表皮のハリや弾力を維持し、角質層上層では表皮の保湿の役割を担うアミノ酸を供給するものであることが知られている。 For example, the filaggrin is a protein contained in keratohyalin granules present in the granule layer on the inner side of the stratum corneum, and is synthesized from profilaggrin. It is known that the synthesized filaggrin plays a role of holding the keratin fibers together in the lower layer of the stratum corneum and is hydrolyzed into amino acids and the like in the upper layer of the stratum corneum along with keratinization of keratinocytes. That is, filaggrin is known to maintain the skin viscoelasticity of the epidermis in the lower layer of the stratum corneum, maintain firmness and elasticity of the epidermis, and supply the amino acid that plays a role of moisturizing the epidermis in the upper layer of the stratum corneum. ..
また、インボルクリン、ロリクリン、又は酵素としてのトランスグルタミナーゼ−１も、角化細胞が角質細胞になる角化過程の各段階の反応を促す蛋白質であることが知られている。 Involucrin, loricrin, or transglutaminase-1 as an enzyme is also known to be a protein that promotes reactions at each stage of the keratinization process in which keratinocytes become keratinocytes.
これらのことから、表皮におけるフィラグリン、インボルクリン、ロリクリン、トランスグルタミナーゼ−１の産生量が減少すると、角質層の正常な形成が妨げられ、皮膚のバリア機能、保湿機能、又は粘弾性機能が低下し得る。そして、肌荒れ、乾燥肌等の皮膚症状を呈したり、アトピー性皮膚炎、乾癬、乾皮症、座瘡等の皮膚疾患を発症したりするようになり得る。また、毛穴が目立つ、又はハリや弾力が低下するといった美容上の問題が発生し得る。
これに対して、表皮における角化過程の各段階に関与するフィラグリン、インボルクリン、トランスグルタミナーゼ−１、ロリクリンといった蛋白質の産生を促進することにより、角質層の正常な形成を促すことができる。そして、角質層の正常な形成を促し、表皮の角化を正常化することにより、毛穴の目立ち、乾燥肌、肌のハリの低下、肌荒れ、アトピー性皮膚炎等が軽減され得る。
From these, when the production amount of filaggrin, involucrin, loricrin, transglutaminase-1 in the epidermis is decreased, normal formation of the stratum corneum is prevented, and the skin barrier function, moisturizing function, or viscoelastic function may be reduced. .. Then, skin symptoms such as rough skin and dry skin may be exhibited, and skin diseases such as atopic dermatitis, psoriasis, xeroderma and acne may develop. In addition, cosmetic problems such as conspicuous pores or reduced elasticity and elasticity may occur.
On the other hand, by promoting production of proteins such as filaggrin, involucrin, transglutaminase-1, and loricrin, which are involved in each stage of the keratinization process in the epidermis, normal formation of the stratum corneum can be promoted. Then, by promoting the normal formation of the stratum corneum and normalizing the keratinization of the epidermis, conspicuous pores, dry skin, reduced skin firmness, rough skin, atopic dermatitis, etc. can be reduced.
前記表皮角化正常化剤の製造方法としては、例えば、Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ ｖａｒ ｃｈｕｎｇｋｏｏｋｊａｎｇ，ＫＣＴＣ ０６９７ＢＰ菌株などのＢａｃｉｌｌｕｓ属の微生物が産生する粗ポリグルタミン酸を含む培養液を限外ろ過膜にて分子量ごとに分画し、分画したものを酸により沈殿処理し、沈殿処理後の酸沈殿物（スラッジ）を水に懸濁して、さらに懸濁液状態でｐＨ３〜４に調整して加水分解することにより、加水分解ポリグルタミン酸を得る方法を採用することができる。
前記表皮角化正常化剤の製造においては、表皮角化正常化剤が表皮の角化をより正常化し得るという点で、粗ポリグルタミン酸などのポリグルタミン酸を酸により沈殿処理した後の酸沈殿物（スラッジ）を加水分解すること、即ち、粗ポリグルタミン酸などのポリグルタミン酸の酸沈殿物を加水分解処理することが好ましい。
前記加水分解ポリグルタミン酸又はその塩は、そのまま表皮角化正常化剤として用いることもでき、さらに水などの溶媒を加えて、含有率を調整した表皮角化正常化剤として用いることもできる。製造された表皮角化正常化剤は、含まれている加水分解ポリグルタミン酸の平均分子量が実施例に記載されたＧＰＣによる方法で測定される。
As a method for producing the epidermal keratinization normalizing agent, for example, a culture solution containing crude polyglutamic acid produced by a microorganism of the genus Bacillus such as Bacillus subtilis var chungkookang, KCTC 0697BP strain is separated by molecular weight by an ultrafiltration membrane. The fractionated and fractionated product is subjected to a precipitation treatment with an acid, the acid precipitate (sludge) after the precipitation treatment is suspended in water, and further adjusted to pH 3 to 4 in a suspension state and hydrolyzed. A method of obtaining hydrolyzed polyglutamic acid can be adopted.
In the production of the epidermal keratinization normalizing agent, in that the epidermal keratinization normalizing agent can further normalize the keratinization of the epidermis, the acid precipitate after polyglutamic acid such as crude polyglutamic acid is precipitated with an acid. It is preferable to hydrolyze (sludge), that is, to hydrolyze an acid precipitate of polyglutamic acid such as crude polyglutamic acid.
The hydrolyzed polyglutamic acid or a salt thereof can be used as it is as a skin keratinization normalizing agent, or can be used as a skin keratinization normalizing agent having a content adjusted by further adding a solvent such as water. The average molecular weight of the hydrolyzed polyglutamic acid contained in the manufactured epidermal keratinization normalizing agent is measured by the GPC method described in Examples.
なお、前記表皮角化正常化剤は、フィラグリン、インボルクリン、ロリクリン、トランスグルタミナーゼ−１の各蛋白質をコードするｍＲＮＡの発現を促進することから、フィラグリン産生促進剤、インボルクリン産生促進剤、ロリクリン産生促進剤、又はトランスグルタミナーゼ−１産生促進剤として用いることもできる。 In addition, the epidermal keratinization normalizing agent, filaggrin, involucrin, loricrin, since it promotes the expression of mRNA encoding each protein of transglutaminase-1, filaggrin production promoter, involucrin production promoter, loricrin production promoter Alternatively, it can be used as a transglutaminase-1 production promoter.
次に、本発明の皮膚外用剤の実施形態について説明する。本実施形態の皮膚外用剤は、前記表皮角化正常化剤を含むものである。
前記表皮角化正常化剤は、通常、加水分解ポリグルタミン酸又はその塩が０．００１〜２０重量％の含有率になるように、好ましくは、０．０２〜１０重量％、より好ましくは、０．０５〜１．０重量％の含有率になるように前記皮膚外用剤に配合される。なお、該含有率は、表皮角化正常化剤が、加水分解ポリグルタミン酸を含んだ水溶液などである場合は、表皮角化正常化剤に含まれる加水分解ポリグルタミン酸又はその塩の上述した含有率を用いて、固形物換算により求める。固形物換算は、表皮角化正常化剤に含まれる溶媒を凍結乾燥により除去した後、加水分解ポリグルタミン酸又はその塩の固形物の量から算出により行う。
Next, an embodiment of the external preparation for skin of the present invention will be described. The external preparation for skin of the present embodiment contains the normalizing agent for keratinization of epidermis.
The normalizing agent for skin keratinization is usually 0.02 to 10% by weight, more preferably 0, so that the content of hydrolyzed polyglutamic acid or a salt thereof is 0.001 to 20% by weight. The external preparation for skin is blended so as to have a content of 0.05 to 1.0% by weight. Incidentally, the content rate, when the epidermal keratinization normalizing agent is an aqueous solution containing hydrolyzed polyglutamic acid, etc., the above-mentioned content rate of hydrolyzed polyglutamic acid or a salt thereof contained in the epidermal keratinization normalizing agent. Is calculated by converting into solid matter. The solid content is calculated by removing the solvent contained in the epidermal keratinization normalizing agent by freeze-drying and then calculating from the solid content of hydrolyzed polyglutamic acid or a salt thereof.
前記皮膚外用剤は、例えば、表皮正常化用外用剤として用いられ得る。また、表皮正常化用化粧料などの化粧料（化粧品）、表皮正常化用医薬部外品などの医薬部外品、医薬品等の態様で用いられ得る。 The external preparation for skin can be used, for example, as an external preparation for normalizing the epidermis. Further, it may be used in the form of cosmetics (cosmetics) such as cosmetics for normalizing the epidermis, quasi-drugs such as quasi-drugs for normalizing epidermis, and pharmaceuticals.
前記皮膚外用剤の具体的な態様としては、例えば、１）局所又は全身用の皮膚洗浄料又は皮膚塗布用化粧料類、２）頭皮や頭髪に適用する頭皮又は頭髪化粧料類、３）浴湯に投じて使用する浴用化粧料類、４）人体用の消臭防臭用化粧料、５）洗口剤等の口腔用化粧料類、６）皮膚貼付用シート、化粧用コットン、ウエットティッシュなどに担持されてなるシート状化粧料類が挙げられる。また、前記皮膚外用剤は、固形状、溶液状、ゲル状、エマルジョン状などの形態になり得るものであり、また、シート状担体、スプレー、アンプル、カプセル、粉末（パウダー）など利用上適宜適当な剤型に適用されて用いられ得る。 Specific embodiments of the external preparation for skin include, for example, 1) topical or systemic skin cleansers or cosmetics for skin application, 2) scalp or hair cosmetics applied to scalp and hair, and 3) baths. Bath cosmetics used in hot water, 4) Deodorant and deodorant cosmetics for human body, 5) Oral cosmetics such as mouthwash, 6) Skin patch sheet, cosmetic cotton, wet tissue, etc. The sheet-shaped cosmetics supported by the above are listed. Further, the external preparation for skin may be in the form of solid, solution, gel, emulsion or the like, and is suitable for use as a sheet carrier, spray, ampoule, capsule, powder (powder), etc. It can be used by being applied to various dosage forms.
皮膚塗布用化粧料類としては、具体的には、例えば、ローション、乳液、クリーム、スプレー、軟膏、ジェル、美容液、オイル、パック、ミストなどの基礎化粧料、ファンデーション、口紅、アイシャドウ、アイライナー、マスカラなどのメークアップ化粧料などが挙げられる。また、皮膚洗浄料類としては、洗顔料、クレンジングなどが挙げられ、頭髪化粧料類としては、シャンプー、リンス、ヘアートリートメント、ヘアートニック、育毛・養毛料などが挙げられる。 As the cosmetics for skin application, for example, basic cosmetics such as lotions, emulsions, creams, sprays, ointments, gels, beauty essences, oils, packs, mists, foundations, lipsticks, eye shadows, eyes, etc. Examples include makeup cosmetics such as liners and mascaras. Examples of the skin cleansing agents include facial cleansers and cleansing agents, and examples of the hair cosmetics include shampoos, conditioners, hair treatments, hairnics, hair restoration and hair nourishing agents.
前記皮膚外用剤には、一般的な化粧料等に配合されている成分が配合され得る。斯かる成分としては、例えば、ブチレングリコール、ジプロピレングリコール、グリセリン等の多価アルコール類、セタノール、ベヘニルアルコール等の高級アルコール類、流動パラフィン、スクワラン等の非極性油剤類、パルミチン酸イソプロピル、ミリスチン酸イソプロピル等のエステル系油剤類、小麦胚芽油やオリーブ油等の植物油類、トリメチルシロキシケイ酸、メチルフェニルポリシロキサン等のシリコン化合物類、パーフルオロポリエーテル等のフッ素化合物類等の液状油剤が挙げられる。
さらに、前記皮膚外用剤に配合され得る成分としては、例えば、水溶性高分子、保湿柔軟化剤、抗酸化剤、収斂剤、美白剤、抗菌剤、抗炎症剤、紫外線吸収剤類、紫外線散乱剤、水溶性ビタミン類、油溶性ビタミン類、酵素等の医薬部外品原料規格、化粧品種別配合成分規格、化粧品原料基準、日本薬局方、食品添加物公定書規格等の成分等が挙げられる。
The above-mentioned external preparation for skin may be blended with components that are commonly used in cosmetics and the like. Examples of such components include polyhydric alcohols such as butylene glycol, dipropylene glycol and glycerin, higher alcohols such as cetanol and behenyl alcohol, non-polar oils such as liquid paraffin and squalane, isopropyl palmitate and isopropyl myristate. And the like, liquid oils such as vegetable oils such as wheat germ oil and olive oil, silicon compounds such as trimethylsiloxysilicic acid and methylphenylpolysiloxane, and fluorine compounds such as perfluoropolyether.
Furthermore, examples of components that can be mixed in the external preparation for skin include water-soluble polymers, moisturizing/softening agents, antioxidants, astringents, whitening agents, antibacterial agents, anti-inflammatory agents, ultraviolet absorbers, and ultraviolet scattering. Ingredients, water-soluble vitamins, oil-soluble vitamins, enzymes, etc., quasi drug raw material specifications, cosmetic ingredient specifications, cosmetic ingredient specifications, Japanese Pharmacopoeia, food additive official standard, etc.
前記皮膚外用剤にさらに配合され得る水溶性高分子としては、例えば、アラビアゴム、クインシード、寒天、カゼイン、デキストリン、ゼラチン、ペクチン、デンプン、カラギーナン、アルギン酸又はその塩、ヒアルロン酸又はその塩、コンドロイチン硫酸又はその塩、エチルセルロース、メチルセルロース、カルボキシメチルセルロース、カルボキシエチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ニトロセルロース、ポリビニルアルコール、ポリビニルピロリドン、ポリビニルメタアクリレート、ポリアクリル酸塩、カルボキシビニルポリマー、ポリエチレンイミン等が挙げられる。 Examples of the water-soluble polymer that can be further added to the external preparation for skin include gum arabic, quince seed, agar, casein, dextrin, gelatin, pectin, starch, carrageenan, alginic acid or a salt thereof, hyaluronic acid or a salt thereof, chondroitin. Sulfuric acid or a salt thereof, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methacrylate, polyacrylic acid salt, carboxyvinyl polymer, polyethyleneimine and the like. ..
前記皮膚外用剤が乳化により調製された乳化物である場合は、該乳化物は、通常、液状油剤を乳化剤によって乳化して調製されてなる。液状油剤の具体的な例としては、例えば、流動パラフィン、スクワラン、イソノナン酸イソノニル、イソノナン酸イソトリデシル、エチルヘキサン酸セチル、トリ２−エチルヘキサン酸グリセリル、トリ（カプリル・カプリン酸）グリセリン、パルミチン酸セチル、イソステアリン酸−２−ヘキシルデシル、ステアリン酸ステアリル、ミリスチン酸イソステアリル、ジ−２−エチルヘキサン酸ネオペンチルグリコール、ジカプリン酸ネオペンチルグリコール、ジイソステアリン酸グリセリル、ジステアリン酸プロピレングリコール等のエステル系液状油剤やコメ油、コメヌカ油、月見草油、リノール酸、コムギ胚芽油、オリーブ油、ホホバ油、ブドウ種子油、カミツレ油、ローズマリ−油、ウイキョウ油等の植物系液状油、卵黄油などの動物系液状油が挙げられる。 When the external preparation for skin is an emulsion prepared by emulsification, the emulsion is usually prepared by emulsifying a liquid oil agent with an emulsifier. Specific examples of the liquid oil agent include, for example, liquid paraffin, squalane, isononyl isononanoate, isotridecyl isononanoate, cetyl ethylhexanoate, glyceryl tri-2-ethylhexanoate, glyceryl tri(capryl-caprate), cetyl palmitate. , 2-hexyldecyl isostearate, stearyl stearate, isostearyl myristate, neopentyl glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glyceryl diisostearate, propylene glycol distearate, etc. Plant oils such as rice oil, rice bran oil, evening primrose oil, linoleic acid, wheat germ oil, olive oil, jojoba oil, grape seed oil, chamomile oil, rosemary oil, fennel oil, and animal liquid oils such as egg yolk oil Can be mentioned.
前記乳化物の調製に用いられる乳化剤としては、例えば、脂肪酸モノグリセリド、ポリオキシエチレン脂肪酸エステル、ポリオキシエチレンアルキルエーテル、ポリグリセリン脂肪酸エステル等の非イオン系界面活性剤、塩化ベンザルコニウム等のカチオン系界面活性剤、両性界面活性剤、アニオン界面活性剤等が挙げられる。 Examples of the emulsifier used in the preparation of the emulsion include nonionic surfactants such as fatty acid monoglyceride, polyoxyethylene fatty acid ester, polyoxyethylene alkyl ether, and polyglycerin fatty acid ester, and cationic agents such as benzalkonium chloride. Surfactants, amphoteric surfactants, anionic surfactants and the like can be mentioned.
前記皮膚外用剤は、さらにキチン、キトサン又はそれらの誘導体を含み得る。キチン、キトサン又はそれらの誘導体としては、特に限定されるものではなく、例えば、カルボキシメチルキチン、カルボキシメチルキトサン、キトサンのグリコール酸塩、ピロリドンカルボン酸塩、乳酸塩、アスコルビン酸塩等の塩類、部分ミリストイル化キトサンピロリドンカルボン酸（例えば、商品名「ＰＭ−キトサン」ピアス株式会社製）等の部分アシル化キトサン塩、部分ミリストイル化カルボキシメチルキトサン（例えば、商品名「ＭＣ−キトサン」ピアス株式会社製））等の部分アシル化カルボキシメチルキトサン等が挙げられる。 The external preparation for skin may further contain chitin, chitosan or a derivative thereof. Chitin, chitosan or derivatives thereof are not particularly limited, and examples thereof include carboxymethyl chitin, carboxymethyl chitosan, glycolates of chitosan, pyrrolidone carboxylates, lactates, salts such as ascorbates, and partial moieties. Partially acylated chitosan salts such as myristoylated chitosan pyrrolidonecarboxylic acid (for example, trade name "PM-chitosan" Pierce Co., Ltd.), partially myristoylated carboxymethyl chitosan (for example, trade name "MC-chitosan" Pierce Co., Ltd.) ) Etc. partially acylated carboxymethyl chitosan and the like.
なお、上記例示した化粧料などの前記皮膚外用剤は、従来公知の一般的な方法によって製造できる。また、前記表皮角化正常化剤は、該表皮角化正常化剤を含む皮膚外用剤を皮膚に塗布するなどして皮膚と接するように用いる化粧方法により使用することができる。 The external preparation for skin such as the cosmetics exemplified above can be produced by a conventionally known general method. Further, the above-mentioned epidermal keratinization normalizing agent can be used by a cosmetic method in which it is used so as to come into contact with the skin by applying an external skin preparation containing the epidermal keratinization normalizing agent to the skin.
本実施形態の表皮角化正常化剤及び皮膚外用剤は、上記例示の通りであるが、本発明は、上記例示の表皮角化正常化剤及び皮膚外用剤に限定されるものではない。また、本発明では、一般の表皮角化正常化剤及び皮膚外用剤において採用される種々の形態を、本発明の効果を損ねない範囲で採用することができる。 The epidermal keratinization normalizing agent and the skin external preparation of the present embodiment are as described above, but the present invention is not limited to the epidermal keratinization normalizing agent and the skin external preparation. Further, in the present invention, various forms employed in a general epidermal keratinization normalizing agent and a skin external preparation can be adopted within a range not impairing the effects of the present invention.
次に、実施例を挙げて本発明をさらに詳しく説明するが、本発明はこれらに限定されるものではない。 Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
まず、以下に示すようにして、表皮角化正常化剤を製造した。その詳細について、説明する。 First, an epidermal keratinization normalizing agent was produced as described below. The details will be described.
（実施例１）
Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ ｖａｒ ｃｈｕｎｇｋｏｏｋｊａｎｇ，ＫＣＴＣ ０６９７ＢＰ菌株を下記の培養条件で培養した。
培地：（Ｌ−グルタミン酸 ４％、グルコース ３％、（ＮＨ4）2ＳＯ4 １％、
Ｎａ−ｃｉｔｒａｔｅ １％、ＫＨ2ＰＯ4 ０.２７％、
Ｎａ2ＨＰＯ4 ０.４２％、ＮａＣｌ ０.０５％、ＭｇＳＯ4 ０.３％、
ビタミン溶液１ｍｌ／Ｌが添加されたＧＳ培地、ｐＨ７．０）
培養：３７℃で５日間
さらに、培養後の粗ポリグルタミン酸含有培養液を限外ろ過膜にて分画した。分画したものに対して塩酸を用いた酸沈殿処理を行い、その後、酸沈殿物（スラッジ）を水に懸濁し、塩酸水溶液によってｐＨ３．５に調整し、懸濁液状態で加水分解処理を行った。
そして、加水分解処理により生じた加水分解ポリグルタミン酸を含む懸濁液を得て、該懸濁液に１重量％水酸化カリウム水溶液を加えて水溶液にし、ＧＰＣ（ゲル浸透クロマトグラフィー）によって、ポリグルタミン酸の平均分子量別に分画して、加水分解ポリグルタミン酸の平均分子量が４００を示す水溶液（加水分解ポリグルタミン酸のカリウム塩を含む）を調製した。該水溶液に対して凍結乾燥を行って水などの溶媒を取り除き、固形物を得て、該固形物をそのまま表皮角化正常化剤とすることで表皮角化正常化剤を製造した。製造した表皮角化正常化剤は、後述する各種の評価に用いた。
(Example 1)
The Bacillus subtilis var chungkookang, KCTC 0697BP strain was cultured under the following culture conditions.
Medium: (L-glutamic acid 4%, glucose 3%, (NH 4) 2 SO 4 1%,
Na-citrate 1%, KH 2 PO 4 0.27%,
Na 2 HPO 4 0.42%, NaCl 0.05%, MgSO 4 0.3%,
(GS medium supplemented with 1 ml/L of vitamin solution, pH 7.0)
Culturing: 5 days at 37° C. Further, the crude polyglutamic acid-containing culture solution after culturing was fractionated by an ultrafiltration membrane. The fractionated product is subjected to acid precipitation treatment using hydrochloric acid, and then the acid precipitate (sludge) is suspended in water, adjusted to pH 3.5 with a hydrochloric acid aqueous solution, and hydrolyzed in suspension. went.
Then, a suspension containing hydrolyzed polyglutamic acid generated by the hydrolysis treatment is obtained, and a 1 wt% potassium hydroxide aqueous solution is added to the suspension to form an aqueous solution, and the polyglutamic acid is obtained by GPC (gel permeation chromatography). Was fractionated according to the average molecular weight of (1) to prepare an aqueous solution (containing a potassium salt of hydrolyzed polyglutamic acid) in which the average molecular weight of hydrolyzed polyglutamic acid was 400. Lyophilization was performed on the aqueous solution to remove a solvent such as water to obtain a solid matter, and the solid matter was directly used as a skin keratinization normalizing agent to produce a skin keratinization normalizing agent. The manufactured epidermal keratinization normalizing agent was used for various evaluations described later.
加水分解ポリグルタミン酸（ＰＧＡ）の平均分子量は、以下のようにして求めた。即ち、カラムとしては、Ｖｉｓｃｏｔｅｋ社製「ＧＭＰＷＸＬ」（２本連結）を用い、溶離液としては、０．１Ｍ硝酸ナトリウムを用い、検出器としては、Ｖｉｓｃｏｔｅｋ社製「ＬＲ１２５ Ｌａｓｅｒ Ｒｅｆｒａｃｔｏｍｅｔｅｒ」を用い、４０℃で示差屈折率により検出を行った。また、標準分子量物質としてポリエチレングリコール（Ａｍｅｒｉｃａｎ Ｐｏｌｙｍｅｒ Ｓｔａｎｄａｒｄｓ社製）の分子量が３５０，７００，１５００，２５００，５２５０，１０２２５，１４５００の標準サンプルを用い、測定した結果に基づき検量線を作成し、この検量線から求めた値をポリエチレングリコール換算の平均分子量として求めた。
なお、平均分子量は、重量平均分子量（Ｍｗ）の値である。また、ＧＰＣチャートにおいて、ベースラインにより分割される複数のピークがあるときは、各ピークそれぞれについて平均分子量を求めたものを平均分子量の値として採用する。
The average molecular weight of hydrolyzed polyglutamic acid (PGA) was determined as follows. That is, as a column, "GMPWXL" manufactured by Viscotek (two linked) was used, as an eluent, 0.1 M sodium nitrate was used, and as a detector, "LR125 Laser Refractometer" manufactured by Viscotek was used, and 40 Detection was performed by differential refractive index at °C. In addition, polyethylene glycol (manufactured by American Polymer Standards) having a molecular weight of 350,700,1500,2500,5250,10225,14500 as a standard molecular weight substance was used as a standard sample, and a calibration curve was prepared based on the measurement results. The value obtained from the line was obtained as the average molecular weight in terms of polyethylene glycol.
The average molecular weight is the value of the weight average molecular weight (Mw). Further, in the GPC chart, when there are a plurality of peaks divided by the baseline, the average molecular weight obtained for each peak is adopted as the value of the average molecular weight.
（実施例２〜４）
実施例１と同様な操作により、加水分解ポリグルタミン酸（ＰＧＡ）の平均分子量が、それぞれ１０００、２０００、１００００を示す加水分解水溶液から調製した固形状の表皮角化正常化剤を各実施例でそれぞれ製造した。
(Examples 2 to 4)
By the same procedure as in Example 1, solid epidermal keratinization normalizing agents prepared from hydrolyzed aqueous solutions each showing an average molecular weight of hydrolyzed polyglutamic acid (PGA) of 1,000, 2000, and 10,000 are respectively used in Examples. Manufactured.
（実施例５〜８）
実施例１と同様な操作により、加水分解ポリグルタミン酸（ＰＧＡ）の平均分子量が、それぞれ８００、９００、１２００、１５００を示す加水分解水溶液から調製した固形状の表皮角化正常化剤を各実施例でそれぞれ製造した。
(Examples 5 to 8)
By the same operation as in Example 1, solid epidermal keratinization normalizing agents prepared from hydrolyzed aqueous solutions showing average molecular weights of hydrolyzed polyglutamic acid (PGA) of 800, 900, 1200 and 1500, respectively, were used. Manufactured respectively.
（実施例９）
実施例１と同様な操作により、加水分解ポリグルタミン酸（ＰＧＡ）の平均分子量が１０万を示す加水分解水溶液から調製した固形状の表皮角化正常化剤を製造した。
(Example 9)
By the same operation as in Example 1, a solid epidermal keratinization normalizing agent prepared from a hydrolyzed aqueous solution showing an average molecular weight of hydrolyzed polyglutamic acid (PGA) of 100,000 was produced.
（比較例１）
実施例１で行った加水分解処理を行わず平均分子量が１００万を示す水溶液を調製し、実施例１と同様な操作により該水溶液から調製したポリグルタミン酸（固形状）を製造した。
(Comparative Example 1)
An aqueous solution having an average molecular weight of 1,000,000 was prepared without carrying out the hydrolysis treatment carried out in Example 1, and polyglutamic acid (solid form) prepared from the aqueous solution was produced by the same operation as in Example 1.
次に、製造した表皮角化正常化剤等について、各種の評価を行った。その詳細を以下に説明する。 Next, various evaluations were performed on the manufactured epidermal keratinization normalizing agent and the like. The details will be described below.
＜ｍＲＮＡの発現促進作用の評価＞
表皮角化正常化剤による、フィラグリン、インボルクリン、トランスグルタミナーゼ−１、及びロリクリンをコードするｍＲＮＡの発現促進作用について、以下の方法によって評価した。
即ち、三次元ヒト皮膚モデル（東洋紡社製、「ＴＥＳＴＳＫＩＮ−ｈｉｇｈ」）の表面に、実施例１〜４，９の表皮角化正常化剤（０．０５重量％、０．１重量％、又は１．０重量％濃度）の水溶液を５０μｌ垂らし、３７℃、５容量％ＣＯ2存在下で２４時間培養した。
培養後、皮膚モデル表面を生理食塩水で１０回洗浄し、ＲＮＡ抽出試薬であるＲＮＡｉｓｏ Ｐｌｕｓ（ＴＡＫＡＲＡ社製）を用いて、バイオプシンによって採取された皮膚組織から総ＲＮＡを抽出し評価用サンプルとした。
また、表皮角化正常化剤を配合していない精製水を垂らして培養した皮膚モデルから同様にＲＮＡを抽出し、対照サンプルとした。さらに、比較例１のポリグルタミン酸を用いて同様に調製したサンプルも準備した。各サンプルにつき２．５μｇのＲＮＡからｃＤＮＡを定法に従い合成した。
<Evaluation of mRNA expression promoting action>
The expression promoting action of mRNAs encoding filaggrin, involucrin, transglutaminase-1, and loricrin by the epidermal keratinization normalizing agent was evaluated by the following method.
That is, on the surface of a three-dimensional human skin model (manufactured by Toyobo Co., Ltd., "TESTSKIN-high"), the skin keratinization normalizing agent of Examples 1 to 4 and 9 (0.05% by weight, 0.1% by weight, or 50 μl of an aqueous solution (concentration of 1.0% by weight) was dropped and cultured at 37° C. in the presence of 5% by volume of CO 2 for 24 hours.
After culturing, the surface of the skin model was washed 10 times with physiological saline, and total RNA was extracted from the skin tissue collected by biopsin using RNAiso Plus (manufactured by TAKARA), which is an RNA extraction reagent, to obtain a sample for evaluation. .
Further, RNA was similarly extracted from a skin model in which purified water containing no normalizing agent for epidermal keratinization was dripped and used as a control sample. Further, a sample prepared in the same manner using the polyglutamic acid of Comparative Example 1 was also prepared. CDNA was synthesized from 2.5 μg of RNA for each sample according to a standard method.
合成したｃＤＮＡをリアルタイムＰＣＲ装置「Ｒｅａｌ Ｔｉｍｅ ＰＣＲ Ｓｙｓｔｅｍ」又は「Ｐｏｗｅｒ ＳＹＢＲ Ｇｒｅｅｎ ＰＣＲ Ｍａｓｔｅｒ Ｍｉｘ」（いずれもＡｐｐｌｉｅｄ Ｂｉｏｓｙｓｔｅｍｓ社製）を用いて、フィラグリン遺伝子、インボルクリン遺伝子、トランスグルタミナーゼ−１遺伝子、ロリクリン遺伝子、及び内部標準遺伝子としてのＲＰＬＰ２遺伝子に対して、それぞれの遺伝子に特異的なプライマーを用いてＰＣＲ反応で増幅を行い、遺伝子発現量を測定した。なお、ＰＣＲ反応温度条件は、酵素活性化及び初期変性として、５０℃２分、９５℃１０分間の反応を行った後、９５℃１５秒のＤＮＡ変性反応と６０℃１分間のアニーリング／伸長反応とを所定回数のサイクルで行った。用いた各プライマーの塩基配列を下記に示す。 The synthesized cDNA was analyzed using a real-time PCR device "Real Time PCR System" or "Power SYBR Green PCR Master Mix" (all are manufactured by Applied Biosystems), and the filaggrin gene, the involucrin gene, the transglutaminase-1 gene, the loricrin gene, and the loricrin gene, The RPLP2 gene as an internal standard gene was amplified by PCR using primers specific to each gene, and the gene expression level was measured. The PCR reaction temperature conditions are as follows: enzyme activation and initial denaturation: 50° C. for 2 minutes and 95° C. for 10 minutes, followed by DNA denaturation reaction at 95° C. for 15 seconds and annealing/extension reaction at 60° C. for 1 minute. And was performed in a predetermined number of cycles. The base sequence of each primer used is shown below.
＜プライマー（フィラグリン）＞
Forward : 5’-atgagcaggcacgagacaa- 3’ （primer1）配列番号１
Reverse : 5’-tgtccacgaatggtgtcct- 3’ （primer2）配列番号２
<Primer (Filaggrin)>
Forward :5'-atgagcaggcacgagacaa- 3'(primer1) SEQ ID NO: 1
Reverse :5'-tgtccacgaatggtgtcct-3' (primer2) SEQ ID NO: 2
＜プライマー（インボルクリン）＞
Forward : 5’- tgcctcagccttactgtgagt- 3’ （primer3）配列番号３
Reverse : 5’- tcatttgctcctgatgggta- 3’ （primer4）配列番号４
<Primer (Involucrin)>
Forward: 5'- tgcctcagccttactgtgagt- 3'(primer3) SEQ ID NO: 3
Reverse :5'- tcatttgctcctgatgggta- 3'(primer4) SEQ ID NO: 4
＜プライマー（トランスグルタミナーゼ−１）＞
Forward : 5’- ccccaagagactagcagtgg- 3’ （primer5）配列番号５
Reverse : 5’- aaggcgtgtcgtacttcatgt- 3’ （primer6）配列番号６
<Primer (transglutaminase-1)>
Forward: 5'- ccccaagagactagcagtgg- 3'(primer5) SEQ ID NO: 5
Reverse :5'- aaggcgtgtcgtacttcatgt- 3'(primer6) SEQ ID NO: 6
＜プライマー（ロリクリン）＞
Forward : 5’- actcacccttcctggtgct- 3’ （primer7）配列番号７
Reverse : 5’- gggtgggctgctttttct- 3’ （primer8）配列番号８
<Primer (Loliclin)>
Forward: 5'- actcacccttcctggtgct- 3'(primer7) SEQ ID NO: 7
Reverse :5'- gggtgggctgctttttct- 3'(primer8) SEQ ID NO: 8
＜プライマー（ＲＰＬＰ２）＞
Forward : 5’- gacgaccggctcaacaag- 3’ （primer9）配列番号９
Reverse : 5’- ccccaccagcaggtacac- 3’ （primer10）配列番号１０
<Primer (RPLP2)>
Forward: 5'- gacgaccggctcaacaag-3' (primer9) SEQ ID NO: 9
Reverse :5'- ccccaccagcaggtacac-3' (primer10) SEQ ID NO: 10
各蛋白質をコードする遺伝子の発現促進率は、表皮角化正常化剤を配合していない精製水を用いた対照サンプルにおける値を１００％とする相対値で示した。即ち、例えば、発現促進率が１５０％を示した場合、遺伝子発現性が１．５倍に上昇していることを表す。なお、発現促進率は、２回又は３回の測定における平均値である。
それぞれの結果を表１〜表４に示す。なお、各表における濃度は、各皮膚外用剤におけるポリグルタミン酸（固形物）の濃度を表している。
The expression promotion rate of the gene encoding each protein was shown as a relative value with the value in the control sample using purified water not containing the epidermal keratinization normalizing agent as 100%. That is, for example, when the expression promoting rate is 150%, it means that the gene expression is increased by 1.5 times. The expression promotion rate is an average value in two or three measurements.
The respective results are shown in Tables 1 to 4. The concentration in each table represents the concentration of polyglutamic acid (solid matter) in each external preparation for skin.
表１〜表４から明らかなように、加水分解ポリグルタミン酸（ＰＧＡ）を含む表皮角化正常化剤は、精製水と比較して、フィラグリンをコードする遺伝子、インボルクリンをコードする遺伝子、トランスグルタミナーゼ−１をコードする遺伝子、ロリクリンをコードする遺伝子の発現促進作用に優れていることが認識される。特に、分子量が４００、８００、１０００、２０００を示す表皮角化正常化剤は、１．０％濃度において、精製水を用いた場合に対して数倍の発現促進作用を示し、フィラグリン遺伝子の発現促進作用が非常に優れている。
従って、実施例の表皮角化正常化剤は、皮膚に適用することにより、フィラグリン、インボルクリン、トランスグルタミナーゼ−１、及びロリクリンといった蛋白等の産生を促進し、正常な表皮形成、具体的には例えば正常な角質層形成を促すことが期待できる。
As is clear from Tables 1 to 4, the epidermal keratinization normalizing agent containing hydrolyzed polyglutamic acid (PGA) was compared to purified water in the gene encoding filaggrin, the gene encoding involucrin, transglutaminase- It is recognized that the gene encoding 1 and the gene encoding loricrin are excellent in promoting expression. In particular, the epidermal keratinization normalizing agent showing a molecular weight of 400, 800, 1000, 2000 shows an expression promoting action several times higher than that in the case of using purified water at the concentration of 1.0%, and the expression of the filaggrin gene. Very good accelerating effect.
Therefore, the epidermal keratinization normalizing agent of the example, by applying to the skin, promote the production of filaggrin, involucrin, transglutaminase-1, and proteins such as loricrin, normal epidermal formation, specifically, for example, It can be expected to promote normal stratum corneum formation.
続いて、毛穴目立ちの軽減作用、アトピー性皮膚炎の軽減作用、乾燥肌の軽減作用、肌のハリ・弾力の改善作用を評価すべく、皮膚外用剤としての美容液、スプレー型ローション、乳液、美容液をそれぞれ調製し、ヒトによる実用評価を行った。その詳細について以下に説明する。 Next, in order to evaluate the effect of reducing the appearance of pores, the effect of reducing atopic dermatitis, the effect of reducing dry skin, and the effect of improving the firmness and elasticity of the skin, a beauty essence as a skin external preparation, a spray lotion, an emulsion, Each of the beauty essences was prepared and practically evaluated by humans. The details will be described below.
［毛穴目立ちの軽減作用の評価］
以下に示す処方及び以下に示す方法により、評価用美容液及び比較対照用美容液を調製した。
[Evaluation of the effect of reducing pore conspicuousness]
A cosmetic liquid for evaluation and a cosmetic liquid for comparison and control were prepared by the following formulation and the method described below.
「評価用美容液の処方」
配合比（重量％）
スクワラン ０．５
ポリオキシエチレン（２０Ｅ．Ｏ）ステアリン酸ソルビタン ０．２
ヒドロキシエチルセルロース ０．２
ヒアルロン酸 ０．１
グリセリン ５．０
アロエエキス ０．５
メチルパラベン ０．１
実施例５の表皮角化正常化剤（ＰＧＡ平均分子量：８００） ０．３
精製水 残量（合計：１００にする）
"Prescription of beauty essence for evaluation"
Mixing ratio (wt%)
Squalane 0.5
Polyoxyethylene (20EO) sorbitan stearate 0.2
Hydroxyethyl cellulose 0.2
Hyaluronic acid 0.1
Glycerin 5.0
Aloe extract 0.5
Methylparaben 0.1
Epidermal keratinization normalizing agent of Example 5 (PGA average molecular weight: 800) 0.3
Purified water Remaining amount (total: 100)
美容液は、次のようにして調製した。即ち、油相成分であるスクワランと、界面活性剤としてのポリオキシエチレン（２０Ｅ．Ｏ）ステアリン酸ソルビタンとを７０℃で加熱しながら溶解させて混合した後、この混合物をヒドロキシエチルセルロース、ヒアルロン酸、及びグリセリン等を含む水相に徐々に添加し、ホモミキサー（５０００ｒｐｍ、２分処理）で均一に分散させた。次に、減圧下で３０℃まで冷却し、ホモミキサー（３０００ｒｐｍ、２分処理）で均一に分散させた。そして、脱気、濾過することにより、白濁した美容液を得た。
また、実施例５の表皮角化正常化剤を配合しなかった点以外は同様にして比較対照用美容液を調製した。
The beauty essence was prepared as follows. That is, squalane, which is an oil phase component, and polyoxyethylene (20EO) sorbitan stearate as a surfactant are dissolved by heating at 70° C. and mixed, and then the mixture is mixed with hydroxyethyl cellulose, hyaluronic acid, And gradually added to an aqueous phase containing glycerin and the like, and uniformly dispersed by a homomixer (5000 rpm, 2 minutes treatment). Next, it was cooled to 30° C. under reduced pressure and uniformly dispersed with a homomixer (3000 rpm, 2 minutes treatment). Then, by degassing and filtering, a cloudy beauty essence was obtained.
In addition, a beauty essence for comparison and control was prepared in the same manner except that the skin keratinization normalizing agent of Example 5 was not added.
＜調製した美容液のヒトによる実用評価（毛穴の目立ち）＞
毛穴の目立ちを気にしている女性ボランティア９名が、左右頬部の一方に評価用美容液を、他方に比較対照用美容液を、１日に２回、６週間塗布した。そして、左右頬部の拡大接写写真像から、毛穴目立ちの程度を下記の通り５段階に分類し、その数値の平均値を求めた。
<Practical evaluation by human of the prepared beauty essence (conspicuous pores)>
Nine female volunteers who were concerned about the conspicuous pores applied the evaluation serum to one of the left and right cheeks and the comparison serum to the other cheek twice a day for 6 weeks. Then, from the magnified close-up photograph images of the left and right cheeks, the degree of pore conspicuity was classified into the following 5 levels, and the average value of the numerical values was obtained.
１：毛穴が目立たない
２：毛穴がほとんど目立たない
３：毛穴がやや目立つ
４：毛穴が明らかに目立つ
５：毛穴が目立ち、開きや赤みも観察される
1: Pore is not noticeable 2: Pore is hardly noticeable 3: Pore is slightly noticeable 4: Pore is clearly noticeable 5: Pore is noticeable, and openness and redness are also observed
評価用美容液においては、平均値が使用前は３．９５点であり、使用後は２．１５点であった。一方、比較対照用美容液においては、平均値が使用前は３．８６点であり、使用後は３．４３点であった。評価用美容液は、正常な角質層の形成に寄与し、毛穴目立ちを軽減するものであることが分かった。 In the beauty essence for evaluation, the average value was 3.95 points before use and 2.15 points after use. On the other hand, in the comparative beauty essence, the average value was 3.86 points before use and 3.43 points after use. It was found that the serum for evaluation contributes to the normal formation of the stratum corneum and reduces the conspicuous pores.
［アトピー性皮膚炎の軽減作用の評価］
以下に示す処方及び以下に示す方法により、評価用スプレー型ローション及び比較対照用スプレー型ローションを調製した。
[Evaluation of atopic dermatitis reducing effect]
A spray type lotion for evaluation and a spray type lotion for comparison and control were prepared by the following formulation and method described below.
「評価用スプレー型ローションの処方」
配合比（重量％）
スクワラン ０．０２
セラミド ０．０１
ポリオキシエチレン（２０Ｅ．Ｏ）ステアリン酸ソルビタン ０．０７
グリセリン ３．０
シトルリン ０．１
メチルパラベン ０．１
実施例７の表皮角化正常化剤（ＰＧＡ平均分子量：１２００） ０．５
精製水 残量（合計：１００にする）
"Prescription of evaluation type spray lotion"
Mixing ratio (wt%)
Squalane 0.02
Ceramide 0.01
Polyoxyethylene (20EO) sorbitan stearate 0.07
Glycerin 3.0
Citrulline 0.1
Methylparaben 0.1
Epidermal keratinization normalizing agent of Example 7 (PGA average molecular weight: 1200) 0.5
Purified water Remaining amount (total: 100)
スプレー型ローションは、次のようにして調製した。即ち、油相成分であるスクワランと、界面活性剤としてのポリオキシエチレン（２０Ｅ．Ｏ）ステアリン酸ソルビタンを７０℃で加熱しながら溶解させて混合した後、この混合物をグリセリン等を含む水相に徐々に添加し、ホモミキサー（５０００ｒｐｍ、２分処理）で均一に分散させた。次に、減圧下で３０℃まで冷却し、ホモミキサー（３０００ｒｐｍ、２分処理）で均一に分散させた。そして、脱気、濾過することにより、半透明のローションを得た。斯かるローションをスプレー容器に充填することにより、スプレー型ローションを調製した。
また、実施例７の表皮角化正常化剤を配合しなかった点以外は同様にして比較対照用スプレー型ローションを調製した。
The spray lotion was prepared as follows. That is, squalane, which is an oil phase component, and polyoxyethylene (20EO) sorbitan stearate as a surfactant are dissolved by heating at 70° C. and mixed, and then the mixture is added to an aqueous phase containing glycerin and the like. The mixture was gradually added and uniformly dispersed with a homomixer (5000 rpm, 2 minutes treatment). Next, it was cooled to 30° C. under reduced pressure and uniformly dispersed with a homomixer (3000 rpm, 2 minutes treatment). Then, by degassing and filtering, a semitransparent lotion was obtained. A spray type lotion was prepared by filling such a lotion in a spray container.
A spray lotion for comparison and control was prepared in the same manner except that the skin keratinization normalizing agent of Example 7 was not added.
＜調製したスプレー型ローションのヒトによる実用評価（アトピー性皮膚炎）＞
ステロイド剤等の外用薬を使用していないが、アトピー性皮膚炎の乾燥や赤みを気にしているボランティア１２名が、左右頬部又は左右前腕部の一方に評価用スプレー型ローションを、他方に比較対照用スプレー型ローションを、１日に２回、４週間使用した。そして、左右頬部や左右前腕部の拡大接写写真像から、アトピー性皮膚炎の症状の程度を４段階に分類し、その数値の平均値を求めた。
<Practical evaluation by human of the prepared spray lotion (atopic dermatitis)>
Twelve volunteers who did not use topical drugs such as steroids, but were concerned about dryness and redness of atopic dermatitis, applied an evaluation spray lotion to one of the left and right cheeks or left and right forearms, and the other to the other. The comparative spray lotion was used twice a day for 4 weeks. Then, from the enlarged close-up photograph images of the left and right cheeks and the left and right forearms, the degree of symptoms of atopic dermatitis was classified into four levels, and the average value of the numerical values was obtained.
１：アトピー性皮膚炎の症状は見られない
２：アトピー性皮膚炎の症状がやや見られる
３：アトピー性皮膚炎の症状が見られる
４：アトピー性皮膚炎の症状がかなり見られる
1: No symptoms of atopic dermatitis 2: Some symptoms of atopic dermatitis are seen 3: Some symptoms of atopic dermatitis are seen 4: Some symptoms of atopic dermatitis are seen
評価用スプレー型ローションにおいては、平均値が使用前は３．１２点であり、使用後は２．０２点であった。一方、比較対照用スプレー型ローションにおいては、平均値が使用前は３．１５点であり、使用後は２．９３点であった。評価用スプレー型ローションは、正常な角質層の形成に寄与し、アトピー性皮膚炎の症状を軽減するものであることが分かった。 In the evaluation spray type lotion, the average value was 3.12 points before use and 2.02 points after use. On the other hand, in the spray lotion for comparison and control, the average value was 3.15 points before use and 2.93 points after use. It was found that the evaluation spray type lotion contributes to the formation of a normal stratum corneum and reduces the symptoms of atopic dermatitis.
［乾燥肌の軽減作用の評価］
以下に示す処方及び以下に示す方法により、評価用乳液及び比較対照用乳液を調製した。
[Evaluation of dry skin reducing effect]
An emulsion for evaluation and an emulsion for comparison and control were prepared according to the formulation shown below and the method shown below.
「評価用乳液の処方」
配合比（重量％）
流動パラフィン ０．８
セラミド１ ０．２
ポリオキシエチレン（２０Ｅ．Ｏ）ステアリン酸ソルビタン ０．９
レチノール ０．０２
ビタミンＡ油 ０．０２
セタノール ０．７
ベヘニルアルコール ０．２
ヒドロキシエチルセルロース ０．２
部分ミリストイル化カルボキシメチルキトサン ０．２
ヒアルロン酸 ０．１
グリセリン ８．０
ブチレングリコール ３．０
塩酸ピリドキシン ０．２
ポリグルタミン酸（平均分子量：４０万） ０．２
メチルパラベン ０．１
実施例６の表皮角化正常化剤（ＰＧＡ平均分子量：９００） １．０
精製水 残量（合計：１００にする）
"Emulsion prescription for evaluation"
Mixing ratio (wt%)
Liquid paraffin 0.8
Ceramide 1 0.2
Polyoxyethylene (20EO) sorbitan stearate 0.9
Retinol 0.02
Vitamin A oil 0.02
Cetanol 0.7
Behenyl alcohol 0.2
Hydroxyethyl cellulose 0.2
Partially myristoylated carboxymethyl chitosan 0.2
Hyaluronic acid 0.1
Glycerin 8.0
Butylene glycol 3.0
Pyridoxine hydrochloride 0.2
Polyglutamic acid (average molecular weight: 400,000) 0.2
Methylparaben 0.1
Epidermal keratinization normalizing agent of Example 6 (PGA average molecular weight: 900) 1.0
Purified water Remaining amount (total: 100)
乳液は、次のようにして調製した。即ち、油相成分である流動パラフィン、セタノール、セラミド１、ベヘニルアルコール等と、界面活性剤としてのポリオキシエチレン（２０Ｅ．Ｏ）ステアリン酸ソルビタンとを７０℃で加熱しながら溶解させて混合した後、この混合物をヒドロキシエチルセルロース、ヒアルロン酸、グリセリン等を含む水相に徐々に添加し、ホモミキサー（５０００ｒｐｍ、２分処理）で均一に分散させた。次に、減圧下で３０℃まで冷却し、ホモミキサー（３０００ｒｐｍ、２分処理）で均一に分散させた。そして、脱気、濾過することにより、白濁した乳液を得た。
また、実施例６の表皮角化正常化剤を配合しなかった点以外は同様にして比較対照用乳液を調製した。
The emulsion was prepared as follows. That is, liquid paraffin, cetanol, ceramide 1, behenyl alcohol, etc., which are oil phase components, and polyoxyethylene (20EO) sorbitan stearate as a surfactant are dissolved and mixed while heating at 70° C. This mixture was gradually added to an aqueous phase containing hydroxyethyl cellulose, hyaluronic acid, glycerin, etc., and uniformly dispersed with a homomixer (5000 rpm, 2 minutes treatment). Next, it was cooled to 30° C. under reduced pressure and uniformly dispersed with a homomixer (3000 rpm, 2 minutes treatment). Then, by degassing and filtering, a cloudy milky lotion was obtained.
A comparative emulsion was prepared in the same manner except that the skin keratinization normalizing agent of Example 6 was not added.
＜調製した乳液のヒトによる実用評価（乾燥肌）＞
乾燥肌を気にしているボランティア１３名が、左右頬部の一方に評価用乳液を、他方に比較対照用乳液を、１日に２回、４週間塗布した。そして、左右頬部の拡大接写写真像から、乾燥肌の程度を５段階に分類し、その数値の平均値を求めた。
<Practical evaluation by human of prepared emulsion (dry skin)>
Thirteen volunteers who were concerned about dry skin applied the evaluation emulsion to one of the left and right cheeks and the comparison emulsion to the other cheek twice a day for 4 weeks. Then, the degree of dry skin was classified into 5 levels from the enlarged close-up photograph images of the left and right cheeks, and the average value of the numerical values was obtained.
１：乾燥肌の症状がない
２：乾燥肌の症状がほとんど認められない
３：乾燥肌の症状がやや認められる
４：乾燥肌の症状が認められる
５：乾燥肌の症状がかなり認められる
1: No dry skin symptom 2: Almost no dry skin symptom 3: Some dry skin symptom 4: Some dry skin symptom 5: Significant dry skin symptom
評価用乳液においては、平均値が使用前は４．２３点であり、使用後は２．３３点であった。一方、比較対照用乳液においては、平均値が使用前は４．２１点であり、使用後は３．１６点であった。評価用乳液は、正常な角質層の形成に寄与し、乾燥肌の症状を軽減するものであることが分かった。 In the emulsion for evaluation, the average value was 4.23 points before use and 2.33 points after use. On the other hand, in the comparative emulsion, the average value was 4.21 points before use and 3.16 points after use. It was found that the evaluation emulsion contributes to the normal formation of the stratum corneum and reduces the symptoms of dry skin.
［肌のハリ・弾力の改善作用の評価］
以下に示す処方及び以下に示す方法により、評価用美容液及び比較対照用美容液を調製した。
[Evaluation of skin firmness and elasticity improvement effect]
A cosmetic liquid for evaluation and a cosmetic liquid for comparison and control were prepared by the following formulation and the method described below.
「評価用美容液の処方」
配合比（重量％）
スクワラン ０．８
ポリオキシエチレン（２０Ｅ．Ｏ）ステアリン酸ソルビタン ０．４
酢酸トコフェロール ０．１
パルミチン酸レチノール ０．０２
ヒドロキシエチルセルロース ０．２
カルボキシメチルキトサン ０．２
キサンタンガム ０．１
ヒアルロン酸 ０．１
グリセリン ５．０
メチルパラベン ０．１
実施例８の表皮角化正常化剤（ＰＧＡ平均分子量：１５００） ０．４
精製水 残量（合計：１００にする）
"Prescription of beauty essence for evaluation"
Mixing ratio (wt%)
Squalane 0.8
Polyoxyethylene (20EO) sorbitan stearate 0.4
Tocopherol acetate 0.1
Retinol palmitate 0.02
Hydroxyethyl cellulose 0.2
Carboxymethyl chitosan 0.2
Xanthan gum 0.1
Hyaluronic acid 0.1
Glycerin 5.0
Methylparaben 0.1
Epidermal keratinization normalizing agent of Example 8 (PGA average molecular weight: 1500) 0.4
Purified water Remaining amount (total: 100)
美容液は、次のようにして調製した。即ち、油相成分であるスクワランと、界面活性剤としてのポリオキシエチレン（２０Ｅ．Ｏ）ステアリン酸ソルビタンとを７０℃で加熱しながら溶解させて混合した後、この混合物をヒドロキシエチルセルロース、ヒアルロン酸、及びグリセリン等を含む水相に徐々に添加し、ホモミキサー（５０００ｒｐｍ、２分処理）で均一に分散させた。次に、減圧下で３０℃まで冷却し、ホモミキサー（３０００ｒｐｍ、２分処理）で均一に分散させた。そして、脱気、濾過することにより、白濁した美容液を得た。
また、実施例８の表皮角化正常化剤を配合しなかった点以外は同様にして比較対照用美容液を調製した。
The beauty essence was prepared as follows. That is, squalane, which is an oil phase component, and polyoxyethylene (20EO) sorbitan stearate as a surfactant are dissolved by heating at 70° C. and mixed, and then the mixture is mixed with hydroxyethyl cellulose, hyaluronic acid, And gradually added to an aqueous phase containing glycerin and the like, and uniformly dispersed by a homomixer (5000 rpm, 2 minutes treatment). Next, it was cooled to 30° C. under reduced pressure and uniformly dispersed with a homomixer (3000 rpm, 2 minutes treatment). Then, by degassing and filtering, a cloudy beauty essence was obtained.
A beauty essence for comparison and control was prepared in the same manner except that the skin keratinization normalizing agent of Example 8 was not added.
＜調製した美容液のヒトによる実用評価（肌のハリ、弾力）＞
肌の弾力やハリの低下を気にしている女性ボランティア１１名が、左右頬部の一方に評価用美容液を、他方に比較対照用美容液を、１日に２回、４週間塗布した。そして、終了後、本人評価により、肌の弾力やハリに対する効果について、４段階に分類し、その数値の平均値を求めた。
<Practical evaluation of prepared beauty essence by human (skin elasticity, elasticity)>
Eleven female volunteers who were concerned about the decrease in elasticity and firmness of the skin applied the evaluation serum on one of the left and right cheeks and the comparison serum on the other cheek twice a day for 4 weeks. Then, after the end, the effect on the elasticity and firmness of the skin was classified into four levels by the evaluation of the person, and the average value of the numerical values was obtained.
１：肌の弾力やハリが明らかに改善した
２：肌の弾力やハリが改善した
３：肌の弾力やハリがやや改善した
４：変化は見られない
1: Remarkably improved elasticity and firmness of skin 2: Improved elasticity and firmness of skin 3: Slightly improved elasticity and firmness of skin 4: No change
評価用美容液においては、使用後の平均値は２．２１点であった。一方、比較対照用美容液においては、使用後の平均値は３．７３点であった。評価用美容液は、正常な角質層や表皮形成に付与し、肌の弾力やハリの低下を改善するものであることが分かった。 In the beauty essence for evaluation, the average value after use was 2.21 points. On the other hand, in the beauty essence for comparison and control, the average value after use was 3.73 points. It was found that the evaluation beauty essence is applied to the formation of the normal stratum corneum and the epidermis, and improves the elasticity and firmness of the skin.
Claims (11)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010115637A JP2011241188A (en) | 2010-05-19 | 2010-05-19 | Epidermal keratinization-normalizing agent, external preparation for skin containing the epidermal keratinization-normalizing agent, external preparation for normalizing epidermis, cosmetic, cosmetic for normalizing epidermis, unregulated drug and unregulated drug for normalizing epidermis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010115637A JP2011241188A (en) | 2010-05-19 | 2010-05-19 | Epidermal keratinization-normalizing agent, external preparation for skin containing the epidermal keratinization-normalizing agent, external preparation for normalizing epidermis, cosmetic, cosmetic for normalizing epidermis, unregulated drug and unregulated drug for normalizing epidermis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2011241188A true JP2011241188A (en) | 2011-12-01 |
Family
ID=45408214
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010115637A Pending JP2011241188A (en) | 2010-05-19 | 2010-05-19 | Epidermal keratinization-normalizing agent, external preparation for skin containing the epidermal keratinization-normalizing agent, external preparation for normalizing epidermis, cosmetic, cosmetic for normalizing epidermis, unregulated drug and unregulated drug for normalizing epidermis |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2011241188A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014040398A (en) * | 2012-08-23 | 2014-03-06 | Mikimoto Pharmaceut Co Ltd | Filaggrin production accelerator, involucrin production accelerator, loricrin production accelerator, corneo-desmosin production accelerator, and others |
| WO2017069128A1 (en) * | 2015-10-19 | 2017-04-27 | 味の素株式会社 | Moisturizer and cosmetic containing same |
| US20210275431A1 (en) * | 2018-06-20 | 2021-09-09 | Swiss Skin Power Ag | Skin formulation |
| WO2022202239A1 (en) * | 2021-03-25 | 2022-09-29 | 東洋紡株式会社 | Expression enhancer of moisturizing factor or barrier function factor of epidermis |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01165357A (en) * | 1987-12-18 | 1989-06-29 | Takeda Chem Ind Ltd | Drink containing polyphenols, quality improvement and quality improver thereof |
| JPH07316286A (en) * | 1994-05-26 | 1995-12-05 | Meiji Seika Kaisha Ltd | Production of low-molecular gamma-poly(glutamic acid) |
| JPH08112084A (en) * | 1994-08-24 | 1996-05-07 | Ajinomoto Co Inc | Frozen foods and their production |
| JP2002233391A (en) * | 2001-01-11 | 2002-08-20 | Bioleaders Corp | Salt-tolerant Bacillus subtilis chungutchan strain producing high molecular weight poly-γ-glutamic acid |
| JP2005015347A (en) * | 2003-06-23 | 2005-01-20 | Ichimaru Pharcos Co Ltd | Filaggrin synthesis promoter |
| JP2005532462A (en) * | 2002-07-10 | 2005-10-27 | バイオリーダーズ コーポレイション | Ultra-high molecular weight poly-gamma-glutamic acid and method of using the same |
-
2010
- 2010-05-19 JP JP2010115637A patent/JP2011241188A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01165357A (en) * | 1987-12-18 | 1989-06-29 | Takeda Chem Ind Ltd | Drink containing polyphenols, quality improvement and quality improver thereof |
| JPH07316286A (en) * | 1994-05-26 | 1995-12-05 | Meiji Seika Kaisha Ltd | Production of low-molecular gamma-poly(glutamic acid) |
| JPH08112084A (en) * | 1994-08-24 | 1996-05-07 | Ajinomoto Co Inc | Frozen foods and their production |
| JP2002233391A (en) * | 2001-01-11 | 2002-08-20 | Bioleaders Corp | Salt-tolerant Bacillus subtilis chungutchan strain producing high molecular weight poly-γ-glutamic acid |
| JP2005532462A (en) * | 2002-07-10 | 2005-10-27 | バイオリーダーズ コーポレイション | Ultra-high molecular weight poly-gamma-glutamic acid and method of using the same |
| JP2005015347A (en) * | 2003-06-23 | 2005-01-20 | Ichimaru Pharcos Co Ltd | Filaggrin synthesis promoter |
Non-Patent Citations (1)
| Title |
|---|
| JPN6014015417; 日本香料品学会誌 ３３巻３号, 2009, ｐ．２２５-２２６ * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014040398A (en) * | 2012-08-23 | 2014-03-06 | Mikimoto Pharmaceut Co Ltd | Filaggrin production accelerator, involucrin production accelerator, loricrin production accelerator, corneo-desmosin production accelerator, and others |
| WO2017069128A1 (en) * | 2015-10-19 | 2017-04-27 | 味の素株式会社 | Moisturizer and cosmetic containing same |
| US10406086B2 (en) | 2015-10-19 | 2019-09-10 | Ajinomoto Co., Inc. | Moisturizer and cosmetic including the same |
| US20210275431A1 (en) * | 2018-06-20 | 2021-09-09 | Swiss Skin Power Ag | Skin formulation |
| WO2022202239A1 (en) * | 2021-03-25 | 2022-09-29 | 東洋紡株式会社 | Expression enhancer of moisturizing factor or barrier function factor of epidermis |
| JP2022149766A (en) * | 2021-03-25 | 2022-10-07 | 東洋紡株式会社 | Enhancer for expression of epidermal moisturizing factor or barrier function factor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5289936B2 (en) | Novel low molecular weight hyaluronic acid and / or salt thereof, and cosmetics, pharmaceutical compositions and food compositions using the same | |
| CN103619415B (en) | Exocellular polysaccharide for treatment and/or the nursing of skin, mucous membrane, hair and/or nail | |
| EP2559708B1 (en) | Process for producing zinc hyaluronate, process for producing cosmetic containing zinc hyaluronate, zinc hyaluronate and process for producing the same | |
| JP5530657B2 (en) | Hyaluronic acid enhancer in skin, and topical skin preparation and cosmetic containing the hyaluronic acid enhancer in skin | |
| JP2004203811A (en) | Cosmetics | |
| JP2001514205A (en) | Skin composition | |
| JP2007112785A (en) | Hyaluronidase inhibitor containing poly-gamma-glutamic acid as effective component | |
| JP2011241188A (en) | Epidermal keratinization-normalizing agent, external preparation for skin containing the epidermal keratinization-normalizing agent, external preparation for normalizing epidermis, cosmetic, cosmetic for normalizing epidermis, unregulated drug and unregulated drug for normalizing epidermis | |
| CN1738631A (en) | Topical composition and methods for treatment of aged or environmentally damaged skin | |
| JP2014231487A (en) | Sirtuin gene activator containing shell membrane component and composition using thereof | |
| Baptista et al. | Bacterial polysaccharides: cosmetic applications | |
| JP6234465B2 (en) | Collagen fiber bundling ability enhancer | |
| JPH05301812A (en) | Skin external preparation | |
| JP5024924B2 (en) | Skin barrier function improver | |
| JP5527917B2 (en) | Arginase activity promoter and skin external preparation containing the same | |
| JP2006290873A (en) | Aquaporin expression promoter | |
| JP6089163B1 (en) | Beauty composition | |
| JP2019019104A (en) | Ceramide synthesis promoter and skin external preparation | |
| JP2003113097A (en) | External preparation including aureobasidium culture solution | |
| US10406086B2 (en) | Moisturizer and cosmetic including the same | |
| JP5312733B2 (en) | Moisturizer, cell activator, antioxidant, protease activity promoter, anti-aging agent, whitening agent, anti-inflammatory agent, neutral fat accumulation inhibitor | |
| JP2002265326A (en) | Skin care preparation | |
| JP6589244B2 (en) | Skin preparation | |
| JP2015063510A (en) | Moisturizing gene expression promoter for improving skin moisturizing function | |
| JP7787552B2 (en) | Collagen production promoter, cell proliferation promoter and wrinkle improvement agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130306 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20130801 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140411 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140709 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150306 |