JP6251471B2 - Whitening agent - Google Patents
Whitening agent Download PDFInfo
- Publication number
- JP6251471B2 JP6251471B2 JP2012124684A JP2012124684A JP6251471B2 JP 6251471 B2 JP6251471 B2 JP 6251471B2 JP 2012124684 A JP2012124684 A JP 2012124684A JP 2012124684 A JP2012124684 A JP 2012124684A JP 6251471 B2 JP6251471 B2 JP 6251471B2
- Authority
- JP
- Japan
- Prior art keywords
- present
- whitening agent
- acidic mucopolysaccharide
- whitening
- active ingredient
- 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.)
- Active
Links
- 230000002087 whitening effect Effects 0.000 title claims description 45
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 52
- 230000002378 acidificating effect Effects 0.000 claims description 47
- 239000003795 chemical substances by application Substances 0.000 claims description 26
- 239000004480 active ingredient Substances 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 11
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- 230000008099 melanin synthesis Effects 0.000 claims description 6
- 150000003214 pyranose derivatives Chemical class 0.000 claims description 6
- 235000013922 glutamic acid Nutrition 0.000 claims description 5
- 239000004220 glutamic acid Substances 0.000 claims description 5
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims description 4
- 230000003796 beauty Effects 0.000 claims description 4
- 235000013305 food Nutrition 0.000 claims description 4
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 4
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical group OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 claims 1
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 23
- 239000002609 medium Substances 0.000 description 22
- 239000000203 mixture Substances 0.000 description 21
- 229920001282 polysaccharide Polymers 0.000 description 21
- 239000005017 polysaccharide Substances 0.000 description 21
- 150000004804 polysaccharides Chemical class 0.000 description 21
- 244000005700 microbiome Species 0.000 description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 229920001817 Agar Polymers 0.000 description 8
- 239000008272 agar Substances 0.000 description 8
- 238000012258 culturing Methods 0.000 description 8
- 239000006071 cream Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 description 6
- 238000005374 membrane filtration Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 239000001888 Peptone Substances 0.000 description 5
- 108010080698 Peptones Proteins 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 229940041514 candida albicans extract Drugs 0.000 description 5
- 239000002537 cosmetic Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 229960002989 glutamic acid Drugs 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- 230000003020 moisturizing effect Effects 0.000 description 5
- 235000019319 peptone Nutrition 0.000 description 5
- 239000013535 sea water Substances 0.000 description 5
- 239000000344 soap Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 239000012138 yeast extract Substances 0.000 description 5
- 241001184650 Cobetia Species 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 229920002301 cellulose acetate Polymers 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 238000005342 ion exchange Methods 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 3
- 208000001382 Experimental Melanoma Diseases 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 229920001284 acidic polysaccharide Polymers 0.000 description 3
- 150000004805 acidic polysaccharides Chemical class 0.000 description 3
- 229960000271 arbutin Drugs 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 235000013373 food additive Nutrition 0.000 description 3
- 239000002778 food additive Substances 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 239000012510 hollow fiber Substances 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 235000014214 soft drink Nutrition 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229920001218 Pullulan Polymers 0.000 description 2
- 239000004373 Pullulan Substances 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000006096 absorbing agent Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical group O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 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
- 238000003556 assay Methods 0.000 description 2
- 239000003788 bath preparation Substances 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000000687 hydroquinonyl group Chemical class C1(O)=C(C=C(O)C=C1)* 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 2
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 2
- 229960004705 kojic acid Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 235000013379 molasses Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 235000019423 pullulan Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- AFSDNFLWKVMVRB-UHFFFAOYSA-N Ellagic acid Chemical compound OC1=C(O)C(OC2=O)=C3C4=C2C=C(O)C(O)=C4OC(=O)C3=C1 AFSDNFLWKVMVRB-UHFFFAOYSA-N 0.000 description 1
- ATJXMQHAMYVHRX-CPCISQLKSA-N Ellagic acid Natural products OC1=C(O)[C@H]2OC(=O)c3cc(O)c(O)c4OC(=O)C(=C1)[C@H]2c34 ATJXMQHAMYVHRX-CPCISQLKSA-N 0.000 description 1
- 229920002079 Ellagic acid Polymers 0.000 description 1
- 206010014970 Ephelides Diseases 0.000 description 1
- 240000008620 Fagopyrum esculentum Species 0.000 description 1
- 235000009419 Fagopyrum esculentum Nutrition 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 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
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 229940127408 Melanin Synthesis Inhibitors Drugs 0.000 description 1
- 208000003351 Melanosis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010040829 Skin discolouration Diseases 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000013040 bath agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 239000007854 depigmenting agent Substances 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000909 electrodialysis Methods 0.000 description 1
- 229960002852 ellagic acid Drugs 0.000 description 1
- 235000004132 ellagic acid Nutrition 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- -1 etc.) Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 238000001459 lithography Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000003061 melanogenesis Effects 0.000 description 1
- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229910052697 platinum 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
- 239000002244 precipitate Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241000556533 uncultured marine bacterium Species 0.000 description 1
Images
Landscapes
- Cosmetics (AREA)
Description
本発明は、海洋細菌の産生する酸性ムコ多糖類を有効成分として配合した美白剤に関するものである。 The present invention relates to a whitening agent containing an acidic mucopolysaccharide produced by marine bacteria as an active ingredient.
さらに詳しくは、本発明は海洋細菌の産生する酸性ムコ多糖類またはその生理学的に許容される塩もしくは誘導体を有効成分として含有する美白剤に関するものであり、特にシミ、ソバカス等の予防または治療に有効であって、優れた美白効果を示すと共に保湿性に富み、安定性および皮膚に対する高い安全性を併せ持つ美白剤に関するものである。 More specifically, the present invention relates to a whitening agent containing an acidic mucopolysaccharide produced by marine bacteria or a physiologically acceptable salt or derivative thereof as an active ingredient, and particularly for the prevention or treatment of stains, buckwheat and the like. The present invention relates to a whitening agent that is effective and exhibits an excellent whitening effect, is rich in moisture retention, has both stability and high safety against the skin.
皮膚の着色の原因となるメラニン色素は、日焼け等により組織中にメラニンが産生することに起因していることが知られている。皮膚が日光に起因する紫外線の照射を受けると、皮膚内に存在しているチロシンが酵素チロシナーゼの作用により酵素的に酸化された後、数段階の反応を経て黒色のメラニンへ変化する過程がメラニン色素の生成過程である。 It is known that melanin pigments that cause skin coloring are caused by the production of melanin in tissues by sunburn or the like. When the skin is irradiated with ultraviolet rays caused by sunlight, tyrosine present in the skin is enzymatically oxidized by the action of the enzyme tyrosinase, and then changes to black melanin through several steps of reaction. This is the process of pigment production.
そして従来から、上記メラニンの生成を抑制し、皮膚の美白状態を維持せしめる美白用皮膚外用剤の組成物として、アルブチンなどのハイドロキノン誘導体、エラグ酸、アスコルビン酸およびその配糖体、コウジ酸およびその誘導体等が知られている。 Conventionally, as a composition for a skin whitening external preparation that suppresses the production of melanin and maintains the skin whitening state, hydroquinone derivatives such as arbutin, ellagic acid, ascorbic acid and its glycosides, kojic acid and its Derivatives and the like are known.
しかしこれら美白用皮膚外用剤には、種々の問題点が残されており、実用性の面で問題があった。例えば、美白成分としてのコウジ酸は発ガンの恐れがあること、アルブチンなどのハイドロキノン誘導体は発疹、かぶれなど安全性に問題があった。また、動植物抽出物配合も知られてはいるが、その効果は満足出来るものではなかった。 However, these skin external preparations for whitening still have various problems and have problems in practical use. For example, kojic acid as a whitening component may cause carcinogenesis, and hydroquinone derivatives such as arbutin have safety problems such as rash and rash. Moreover, although the composition of animal and plant extracts is known, the effect is not satisfactory.
そのため、優れた美白効果を示すと共に、安定性および皮膚に対する高い安全性を併せ持つ成分が求められていた。 Therefore, there has been a demand for a component that exhibits an excellent whitening effect and has both stability and high safety against the skin.
一方、乳酸菌が産生するリン酸化多糖類や海洋細菌の作る多糖類に美白作用を持ち、美白剤としての有用性が開示されている(特許文献1〜4)。また、種々の海洋細菌が多糖類を産生することが知られている(特許文献5〜7、非特許文献1〜2)。 On the other hand, phosphorylated polysaccharides produced by lactic acid bacteria and polysaccharides produced by marine bacteria have a whitening effect, and their usefulness as whitening agents are disclosed (Patent Documents 1 to 4). Various marine bacteria are known to produce polysaccharides (Patent Documents 5 to 7, Non-Patent Documents 1 and 2).
本発明は、上記の事情に鑑みなされたもので、優れた美白効果を有し、安定性および皮膚に対して安全性の高い新規な成分を有効成分とする美白剤を提供することを課題とする。 The present invention has been made in view of the above circumstances, and has an object to provide a whitening agent that has an excellent whitening effect and has a novel component that is highly stable and safe for the skin as an active ingredient. To do.
本発明者らは、ヒト皮膚美白剤として使用が可能な物質を求めて、鋭意研究を進めていたところ、抗ウイルス作用を有する物質として知られている海洋細菌が産生する酸性ムコ多糖類にメラノーマ細胞のメラニンの生成を抑制する効果があることを見出し、本発明を完成するに至った。 The present inventors have been eagerly researching for a substance that can be used as a human skin lightening agent, and have found that melanoma is an acidic mucopolysaccharide produced by marine bacteria known as an antiviral substance. It has been found that there is an effect of suppressing the production of melanin in cells, and has completed the present invention.
即ち、本発明は(1)海洋細菌の産生する酸性ムコ多糖類またはその生理学的に許容される塩もしくは誘導体を有効成分として含有することを特徴とする美白剤に関する。
尚、本酸性ムコ多糖類としては、コベチア(Cobetia)属に属し寄託番号がFERM P-21297として寄託されている菌株またはその変異株の培養物より分離精製された酸性ムコ多糖類を用いることが好ましい。これら酸性ムコ多糖類は、本明細書において単に「本酸性ムコ多糖類」と表記する。
本発明の美白剤の有効成分として用いられる海洋細菌が産生する本酸性ムコ多糖類は、次の構造式で示される化合物である。
That is, the present invention relates to (1) a whitening agent characterized by containing an acidic mucopolysaccharide produced by marine bacteria or a physiologically acceptable salt or derivative thereof as an active ingredient.
As the acidic mucopolysaccharide, an acidic mucopolysaccharide separated and purified from the culture of the strain belonging to the genus Cobetia and deposited with the deposit number of FERM P-21297 or its mutant strain is used. preferable. These acidic mucopolysaccharides are simply referred to as “present acidic mucopolysaccharides” in the present specification.
The acidic mucopolysaccharide produced by marine bacteria used as an active ingredient of the whitening agent of the present invention is a compound represented by the following structural formula.
海洋細菌が産生する本酸性多糖類を有効成分とする美白剤は、B-16メラノーマ細胞に対して、細胞毒性を示すことなくメラニン産生を抑制する。 A whitening agent containing the present acidic polysaccharide produced by marine bacteria as an active ingredient suppresses melanin production without showing cytotoxicity against B-16 melanoma cells.
本発明の有効成分である酸性ムコ多糖類は、B-16メラノーマ細胞に対して、細胞毒性を示すことなくメラニン生成を抑制し,皮膚に美白作用をなすので、美白剤として安全で非常に有用である。しかも本酸性ムコ多糖類にはグルタミン酸という天然保湿因子が結合し、皮膚外用剤としての価値ある用件を備えている点でこれまでの多糖類にない有利な材料である。
本発明の有効成分である酸性ムコ多糖類はまた、美容食品などの経口用途にも用いることができる。
The acidic mucopolysaccharide, which is an active ingredient of the present invention, is safe and very useful as a whitening agent because it suppresses melanin production without causing cytotoxicity against B-16 melanoma cells and has a whitening effect on the skin. It is. In addition, natural moisturizing factor called glutamic acid is bound to the acidic mucopolysaccharide, which is an advantageous material not found in conventional polysaccharides in that it has a valuable requirement as an external preparation for skin.
The acidic mucopolysaccharide which is an active ingredient of the present invention can also be used for oral use such as beauty food.
本発明は、上記知見に基づいて完成されたものであり、本酸性ムコ多糖類を有効成分として含有する美白用組成物に関するものである。 This invention is completed based on the said knowledge, and relates to the composition for whitening which contains this acidic mucopolysaccharide as an active ingredient.
本酸性ムコ多糖類については、従来、その誘導体に抗ウイルス作用を有することが知られているが、これを美白剤として使用したという報告はないことからすると上記知見はまさに驚くべきものであった。 As for the present acidic mucopolysaccharide, it has been known that its derivatives have antiviral activity, but the above findings were just amazing because there was no report that it was used as a whitening agent. .
本発明において、美白剤とは、シミ、ソバカス等の予防または治療に有効な皮膚外用剤組成物または経口用組成物であって、化粧品や医薬部外品としてのローション、乳液、クリーム、パック剤、石鹸等の薬用化粧品、および医薬品としてのローション、乳液、クリーム、軟膏等の皮膚外用剤、ならびに美容食品や機能性食品などの経口剤を含むものである。 In the present invention, the whitening agent is an external skin composition or oral composition effective for the prevention or treatment of spots, freckles, etc., and is a lotion, emulsion, cream or pack as a cosmetic or quasi-drug. , Cosmetics such as soap, and skin external preparations such as lotions, emulsions, creams and ointments as pharmaceuticals, and oral preparations such as beauty foods and functional foods.
本発明の美白用皮膚外用剤組成物は、有効成分である本酸性ムコ多糖類と、皮膚外用剤に一般に用いられている各種成分、例えば、油分、界面活性剤、紫外線吸収剤、アルコール、保湿剤、防腐剤、殺菌剤、色剤、粉末、香料、増粘剤、緩衝剤などとを、その剤形にあわせ、本発明の効果を損なわない範囲で適宜配合することにより調製される。
本発明の美白用経口用組成物は、有効成分である本酸性ムコ多糖類と、経口用組成物に一般的に用いられている各種成分、例えば、賦形剤、防腐剤、色剤、香料などとを、その剤形にあわせ、本発明の効果を損なわない範囲で適宜配合することにより調製される。
The skin whitening composition for skin whitening of the present invention comprises the present acidic mucopolysaccharide as an active ingredient, and various components generally used in skin external preparations, such as oils, surfactants, UV absorbers, alcohol, moisturizing agents. It is prepared by appropriately blending agents, preservatives, bactericides, colorants, powders, fragrances, thickeners, buffering agents and the like in accordance with the dosage form so long as the effects of the present invention are not impaired.
The oral whitening composition of the present invention comprises the present active mucopolysaccharide as an active ingredient and various components generally used in oral compositions such as excipients, preservatives, colorants, and fragrances. And the like according to the dosage form, and the like, as long as the effects of the present invention are not impaired.
本発明の美白用組成物に、本酸性ムコ多糖類を配合するに当たっては、これら化合物の美白作用ならびに皮膚の角質透過性等を考慮することが好ましく、一般にはこれら化合物を有効成分として少なくとも0.001重量%以上、好ましくは0.01〜20.0重量%程度添加すればよい。必ずしも有効成分を単離して使用する必要はなく、必要に応じて本発明の効果を損なわない範囲で、本発明の化合物を含む粗精製物を使用することができる。 In blending the acidic mucopolysaccharide with the whitening composition of the present invention, it is preferable to consider the whitening action of these compounds and the skin keratin permeability. 001% by weight or more, preferably about 0.01 to 20.0% by weight may be added. It is not always necessary to isolate and use the active ingredient, and a crude product containing the compound of the present invention can be used as long as the effects of the present invention are not impaired.
本発明の美白用皮膚外用剤の剤型は任意であり、例えば化粧水等の可溶化系、乳液またはクリーム等の乳化系、あるいは軟膏または分散液などの剤型をとることができる。
本発明の美白用経口剤の剤型は任意であり、例えば錠剤、カプセル剤、液剤、シロップ剤などの剤型をとることができる。
こうして所望の美白効果、例えば顔などのシミの発生を防ぐことができ、また既に生成しているシミの脱色に使用できる美白剤が提供される。
The dosage form of the skin external preparation for whitening of the present invention is arbitrary, and for example, a solubilizing system such as lotion, an emulsifying system such as emulsion or cream, or an ointment or dispersion can be used.
The dosage form of the whitening oral preparation of the present invention is arbitrary, and can be in the form of tablets, capsules, liquids, syrups and the like.
In this way, a desired whitening effect, for example, generation of a stain on the face or the like, can be prevented, and a whitening agent that can be used for decolorization of an already produced stain is provided.
(有効成分)
本発明で使用される本酸性ムコ多糖類は、医薬として使用できる程度に精製されたものであれば、種々の方法で調製されたものを用いることができる。本ムコ多糖類の調製方法としては、各種の方法が知られている。例えば、海洋微生物を炭素源として蔗糖、窒素源としてペプトン、酵母エキスを含有する海水を寒天で固めた培地で培養して産生する多糖類を採取、精製して得ることができる。
(Active ingredient)
As the acidic mucopolysaccharide used in the present invention, those prepared by various methods can be used as long as they are purified to such an extent that they can be used as pharmaceuticals. Various methods are known as methods for preparing the present mucopolysaccharide. For example, it can be obtained by collecting and purifying polysaccharides produced by culturing marine microorganisms as sucrose as a carbon source, peptone as a nitrogen source, and seawater containing yeast extract in a medium solidified with agar.
より具体的には、例えば寒天平板培養では、炭素源として蔗糖、窒素源としてペプトン、酵母エキスを含有する多糖類生産用海水培地を寒天で固めた培地においてコベチア(Cobetia)属に属し寄託番号がFERM P-21297として寄託されている菌株またはその変異株を培養し、寒天平板上に生じた粘質物中の本酸性ムコ多糖類を分離、精製して得ることができる。 More specifically, for example, in agar plate culture, sucrose as a carbon source, peptone as a nitrogen source, and a polysaccharide production seawater medium containing yeast extract are agar-solidified in agar and belong to the genus Cobetia. It can be obtained by culturing a strain deposited as FERM P-21297 or a mutant thereof, and isolating and purifying the acidic mucopolysaccharide in the mucilage produced on the agar plate.
本酸性ムコ多糖類を産生する微生物を培養する基本培地としては、多糖類を産生しうる微生物が生育できるものであって、少なくとも炭素源と、窒素源と、各種無機塩と、および微量元素とを適量含有するものが用いられる。さらに好ましくは、前記基本培地として、コベチア(Cobetia)属に属する微生物が生育できるものが用いられる。炭素源としては、グルコース、フラクトース、ガラクトース、シュクロース等の糖、あるいは糖蜜や廃糖蜜が挙げられる。炭素源として1種または2種以上を単独でまたは組み合わせて用いることができる。窒素源としては、硝酸塩、アンモニウム塩等の化合物やペプトン、酵母エキス、アミノ酸などの天然物が挙げられる。窒素源として1種または2種以上を単独でまたは組み合わせて用いることができる。無機塩としては、例えば、リン酸塩、マグネシウム塩、カリウム塩等が挙げられる。無機塩として1種または2種以上を単独でまたは組み合わせて用いることができる。固体培地の場合は寒天を用いる。 As a basic medium for culturing microorganisms that produce this acidic mucopolysaccharide, microorganisms that can produce polysaccharides can grow, and at least a carbon source, a nitrogen source, various inorganic salts, and trace elements Those containing an appropriate amount of are used. More preferably, as the basic medium, one capable of growing microorganisms belonging to the genus Cobetia is used. Examples of the carbon source include sugars such as glucose, fructose, galactose, and sucrose, and molasses and molasses. One or two or more carbon sources can be used alone or in combination. Nitrogen sources include compounds such as nitrates and ammonium salts, and natural products such as peptone, yeast extract and amino acids. One or two or more nitrogen sources can be used alone or in combination. Examples of the inorganic salt include phosphate, magnesium salt, potassium salt and the like. One or two or more inorganic salts can be used alone or in combination. In the case of a solid medium, agar is used.
使用する培地、培地のpH、培地への添加物、培養温度などは通常微生物の培養の際に用いられている条件をそのまま用いることができる。 The conditions usually used for culturing microorganisms can be used as they are for the medium to be used, the pH of the medium, the additives to the medium, the culture temperature and the like.
本酸性ムコ多糖類の産生に用いられる微生物としては、多糖類を産生しうるものであれば特に制限なく使用することができる。好ましくは海洋微生物、さらに好ましくは本酸性ムコ多糖類を産生する能力のある海洋微生物が用いられる。具体的にはコベチア(Cobetia)属細菌が挙げられ、より具体的にはコベチア(Cobetia)属に属し寄託番号がFERM P-21297として寄託されている菌株またはその変異株が挙げられる。本菌株は本発明者らが瀬戸内海において海水より分離した海洋性細菌であり、その分類学的特性は、上記特許文献7に記載されている。 The microorganism used for production of the present acidic mucopolysaccharide can be used without particular limitation as long as it can produce the polysaccharide. Preferably, marine microorganisms, more preferably marine microorganisms capable of producing the present acidic mucopolysaccharide are used. Specific examples include bacteria belonging to the genus Covetia, and more specifically, strains belonging to the genus Cobecia and deposited with a deposit number of FERM P-21297 or mutants thereof. This strain is a marine bacterium isolated from seawater by the present inventors in the Seto Inland Sea, and its taxonomic characteristics are described in Patent Document 7.
本発明における培養条件は、培養時のpHは微生物が生育し、かつ多糖類を産生する範囲であれば制限されないが、通常は6から7.5の範囲のpHが好ましい。培養温度については微生物が生育し、かつ多糖類を産生する範囲であれば制限されないが、25℃から30℃の範囲が多糖類の産生には良好である。培養期間は培養のpHや温度により変化するが、通常2日から5日が適切である。 The culture conditions in the present invention are not limited as long as the pH during culture is a range in which microorganisms can grow and produce polysaccharides, but a pH in the range of 6 to 7.5 is usually preferable. The culture temperature is not limited as long as microorganisms grow and produce polysaccharides, but a range of 25 ° C. to 30 ° C. is good for producing polysaccharides. The culture period varies depending on the culture pH and temperature, but usually 2 to 5 days is appropriate.
前記した培地と微生物を用いて従来法を用いて微生物を培養することにより、本発明の有効成分である本酸性ムコ多糖類が効率的に産生されることとなる。 By culturing microorganisms using the above-mentioned medium and microorganisms using a conventional method, the present acidic mucopolysaccharide, which is an active ingredient of the present invention, is efficiently produced.
本発明に用いられる本酸性ムコ多糖類は、構成糖のモル比がN−アセチル−D−グルコサミン:D−グルクロン酸:L−グルタミン酸が2:1:1(モル濃度比)で、ゲル濾過クロマトグラフィーで測定した平均分子量がプルランを標準として100〜150万であることが好ましい。構成成分の分析には、セルロースアセテート膜電気泳動、または高速液体クロマトグラフィーを用いることができる。この構成成分の分析には、多糖類を2Mのトリフルオロ酢酸(TFA)、または4N-HClで100℃、12時間加水分解し、ロータリーエバポレイターでTFAまたはHClを除いたものを検体とし、中性糖、ウロン酸、有機酸、アミノ酸およびアミノ糖の分析を行う。構成有機酸の分析にはこの他に酵素法を用いることができる。 The acidic mucopolysaccharide used in the present invention has a constituent sugar molar ratio of N-acetyl-D-glucosamine: D-glucuronic acid: L-glutamic acid of 2: 1: 1 (molar concentration ratio) and gel filtration chromatography. It is preferable that the average molecular weight measured by lithography is 100 to 1,500,000 with pullulan as a standard. Cellulose acetate membrane electrophoresis or high performance liquid chromatography can be used for the analysis of the constituent components. For analysis of this component, polysaccharide was hydrolyzed with 2M trifluoroacetic acid (TFA) or 4N-HCl at 100 ° C. for 12 hours, and TFA or HCl was removed with a rotary evaporator as a sample. Analyzes of sexual sugars, uronic acids, organic acids, amino acids and amino sugars. In addition to this, an enzymatic method can be used for analysis of constituent organic acids.
本酸性ムコ多糖類の分子量の測定は、ゲル濾過クロマトグラフィー法を用いることができる。具体的には、Asahipak GFA-7M(昭和電工製)をカラムとする高速液体クロマトグラフィー(島津製)を使用し、0.1M-NaClを移動相とし、分子量既知のプルラン(Shodex STANDARD KIT P-82、昭和電工製)を標準サンプルとして作成した分子量保持時間標準曲線を使用して測定することができる。 The molecular weight of the present acidic mucopolysaccharide can be measured by gel filtration chromatography. Specifically, high-performance liquid chromatography (manufactured by Shimadzu) using Asahipak GFA-7M (manufactured by Showa Denko) as a column, 0.1M-NaCl as the mobile phase, and a pullulan having a known molecular weight (Shodex STANDARD KIT P- 82, manufactured by Showa Denko) as a standard sample, and can be measured using a molecular weight retention time standard curve.
(有効成分の製造方法)
次に、本発明の美白剤の有効成分である本酸性ムコ多糖類の製造方法について、好ましい実施形態を挙げて説明する。尚、本酸性ムコ多糖類の生産方法は以下の製法に限定されない。
好ましい1実施形態としての本酸性ムコ多糖類の製造方法は、(a)前記培地において微生物を培養し多糖類を産生する工程と、(b)産生された本酸性ムコ多糖類を抽出・回収する工程とを有する。
(Method for producing active ingredient)
Next, the production method of the present acidic mucopolysaccharide which is an active ingredient of the whitening agent of the present invention will be described with reference to preferred embodiments. In addition, the production method of this acidic mucopolysaccharide is not limited to the following production method.
The production method of the present acidic mucopolysaccharide as a preferred embodiment includes (a) a step of culturing a microorganism in the medium to produce a polysaccharide, and (b) extracting and recovering the produced acidic mucopolysaccharide. Process.
続いて、前記の実施形態を各工程毎に詳細に説明していく。
前記した本発明の培地を用いることが望ましく、その際に炭素源として蔗糖、窒素源としてペプトン、酵母エキスを用いることがより望ましい。
(a)前記培地において微生物を培養し多糖類を産生する工程
前記のようにして調製した培地を用いて微生物を培養して目的の多糖類を産生させるわけであるが、本酸性ムコ多糖類を得るためには微生物としてコベチア(Cobetia)属の細菌を用いることが好ましい。さらに好ましくはコベチア(Cobetia)属に属し寄託番号がFERM P-21297として寄託されている菌株またはその変異株を用いることが望ましい。微生物として該菌株またはその変異株を用いることで、本酸性ムコ多糖類を効率的に産生することができる。
そして、以下に説明する抽出・回収工程を経ることにより高純度の本酸性ムコ多糖類を高収率で得ることが可能となる。
Subsequently, the embodiment will be described in detail for each step.
It is desirable to use the above-described medium of the present invention, and in this case, it is more desirable to use sucrose as the carbon source, peptone, and yeast extract as the nitrogen source.
(A) Step of culturing microorganisms in the medium to produce polysaccharides The microorganisms are cultured using the medium prepared as described above to produce the target polysaccharide. In order to obtain it, it is preferable to use a bacterium belonging to the genus Cobecia as a microorganism. More preferably, it is desirable to use a strain belonging to the genus Cobetia and deposited with a deposit number of FERM P-21297 or a mutant thereof. The acidic mucopolysaccharide can be efficiently produced by using the strain or a mutant thereof as a microorganism.
And it becomes possible to obtain this acidic mucopolysaccharide of high purity by a high yield by passing through the extraction and collection | recovery process demonstrated below.
(b)産生された所定の多糖類を抽出・回収する工程
上記製造方法で得られた培養液から本酸性ムコ多糖類を抽出する方法としては、従来公知の方法を用いることができる。例えば、培養液をそのまま、あるいは高温で殺菌した後で、遠心分離により菌体を除去し、これをそのまま、あるいは濃縮してから、2〜3倍量のエタノール、イソプロパノール、あるいはアセトン等を加え、沈殿を生じさせる。この沈殿物を再度、水あるいは1〜15%塩化ナトリウム溶液に溶解させた後で、アルコール等による沈殿を2〜3回繰り返し、水で透析を行い、噴霧乾燥や凍結乾燥機等を用いて乾燥させることにより、本酸性ムコ多糖類を得る。これ以外にも電気透析法や限外濾過法も利用することができる。さらに精製するためには、イオン交換、ゲル濾過等の各種クロマトグラフィーや第4級アンモニウム塩による沈殿や塩析などを用いることができる。
(B) Step of Extracting / Recovering the Specified Polysaccharide Produced As a method of extracting the acidic mucopolysaccharide from the culture solution obtained by the above production method, a conventionally known method can be used. For example, after sterilizing the culture solution as it is or at a high temperature, the microbial cells are removed by centrifugation, and after adding or concentrating this, add 2-3 times the amount of ethanol, isopropanol, or acetone, This causes precipitation. After this precipitate is dissolved again in water or 1-15% sodium chloride solution, precipitation with alcohol or the like is repeated 2-3 times, dialyzed with water, and dried using a spray dryer or a freeze dryer. This acidic mucopolysaccharide is obtained. In addition, electrodialysis and ultrafiltration can be used. For further purification, various chromatographies such as ion exchange and gel filtration, precipitation or salting out with a quaternary ammonium salt, and the like can be used.
かくして本酸性ムコ多糖類が産生および回収されることになる。本発明により得られる本酸性ムコ多糖類は特に制限なく種々の用途に使用されうるものであるが、好ましくは上述の美白剤として好適に用いられる。 Thus, the acidic mucopolysaccharide will be produced and recovered. The acidic mucopolysaccharide obtained according to the present invention can be used for various applications without any particular limitation, but is preferably used as the above-described whitening agent.
ここで、本酸性ムコ多糖類は下記構造単位を有するものである。 Here, the present acidic mucopolysaccharide has the following structural units.
本発明では、有効成分として少なくとも0.001重量%以上、好ましくは、0.01〜20重量%の本酸性ムコ多糖類を美白剤に配合する。
この本酸性ムコ多糖類を有効成分として含有する外用美白剤は、通常使用されている皮膚外用剤基材を使用することにより、クリーム、乳液、化粧水等の適当な形態とすることができる。さらに、紫外線吸収剤、紫外線散乱剤、アルブチン等のメラニン合成抑制剤、その他の薬効成分、増粘剤、可塑剤、着色料、香料等、任意の添加物をこの美白剤に含有させることができる。なお、本発明の美白剤の有効成分である本酸性ムコ多糖類については、皮膚に対する毒性も刺激も無く、副作用も無い。また一般に多糖類には保湿効果があること、および本酸性ムコ多糖類には天然保湿因子のグルタミン酸が含まれていることからして、本酸性ムコ多糖類またはそれらの生理学的に許容される塩もしくは誘導体を有効成分として含む本発明の美白剤は、美白効果に加えて好ましい保湿効果を有することは当業者であれば容易に推測できるであろう。
この本酸性ムコ多糖類は、上述のように、美容食品や機能性食品などの美白用経口剤に配合することもできる。
In the present invention, at least 0.001% by weight or more, preferably 0.01 to 20% by weight of the acidic mucopolysaccharide is added to the whitening agent as an active ingredient.
The external whitening agent containing this acidic mucopolysaccharide as an active ingredient can be made into a suitable form such as cream, emulsion, lotion, etc. by using a commonly used skin external preparation base. Further, this whitening agent can contain arbitrary additives such as ultraviolet absorbers, ultraviolet scattering agents, melanin synthesis inhibitors such as arbutin, other medicinal ingredients, thickeners, plasticizers, colorants, and fragrances. . The acidic mucopolysaccharide, which is an active ingredient of the whitening agent of the present invention, is neither toxic nor irritating to the skin and has no side effects. In addition, since the polysaccharide generally has a moisturizing effect, and the acidic mucopolysaccharide contains the natural moisturizing factor glutamic acid, the acidic mucopolysaccharide or a physiologically acceptable salt thereof is used. Alternatively, it can be easily estimated by those skilled in the art that the whitening agent of the present invention containing a derivative as an active ingredient has a preferable moisturizing effect in addition to the whitening effect.
This acidic mucopolysaccharide can also be blended in whitening oral preparations such as beauty foods and functional foods as described above.
以上本発明の美白剤について説明してきたが、本発明の美白剤のメラニン抑制効果を利用することにより、エビなどの変色防止剤といった食品添加物としても用いることも可能である。即ち、本発明の別の態様として、本酸性ムコ多糖類またはその生理学的に許容される塩もしくは誘導体を有効成分として含有することを特徴とする食品添加物が提供される。この場合、食品添加物の使用量は当業者の知識に基づき用途に応じて適宜定まるものである。 Although the whitening agent of the present invention has been described above, it can also be used as a food additive such as a discoloration inhibitor such as shrimp by utilizing the melanin suppressing effect of the whitening agent of the present invention. That is, as another aspect of the present invention, there is provided a food additive comprising the acidic mucopolysaccharide or a physiologically acceptable salt or derivative thereof as an active ingredient. In this case, the amount of food additive used is appropriately determined according to the application based on the knowledge of those skilled in the art.
次に実施例を挙げ、本発明をさらに詳しく説明するが、本発明はこれら実施例になんら制約されるものではない。尚、特記しない限り、百分率(%)は重量基準である。 EXAMPLES Next, although an Example is given and this invention is demonstrated in more detail, this invention is not restrict | limited at all to these Examples. Unless otherwise specified, percentages (%) are based on weight.
(実施例1)
ペプトン0.5%、酵母エキス0.1%、蔗糖3%の組成を有し海水で調製した培地を、温度121℃としたオートクレーブ中で15分間滅菌し、本菌株(FERM P-21297)の斜面培養から、1白金耳を試験管中の上記滅菌培地(10ml)に接種し、25℃の温度で24時間静置培養を行い、次いでこの前培養液を500ml容の三角フラスコ中に上記組成の培地100ml(121℃、15分間滅菌)に接種し、25℃の温度で3日間の静置培養を行った。培養後培養液を遠心分離した後濾過助剤(ラヂオライト#500)を用いてGF-75濾紙(Advantec)で濾過し、菌体を除いた培養濾過液から分子量5万カットの中空糸UF膜モジュール(Spectrum社製)を備えた膜濾過装置により得られる高分子画分を短時間のうちに濃縮、脱塩回収し、活性炭処理し、凍結乾燥により粉末化した。膜濾過装置は東洋紡エンジニアリング社製SYLS-SB04型を用いた。
このようにして得られた多糖画分については、セルロースアセテート膜電気泳動を用いて均一性を確認すると共に、DEAE-セルロースイオン交換カラムクロマト分析、化学分析、核磁気共鳴分析により、公知の本酸性ムコ多糖類であることを確認した。
Example 1
A medium prepared with seawater having a composition of 0.5% peptone, 0.1% yeast extract and 3% sucrose was sterilized in an autoclave at a temperature of 121 ° C. for 15 minutes, and the strain (FERM P-21297) From the slant culture, one platinum loop is inoculated into the above-mentioned sterilized medium (10 ml) in a test tube, and statically cultured at a temperature of 25 ° C. for 24 hours, and then this preculture solution is placed in a 500 ml Erlenmeyer flask. The medium was inoculated into 100 ml (121 ° C., sterilized for 15 minutes) and subjected to stationary culture at 25 ° C. for 3 days. After culturing, the culture broth is centrifuged, filtered through GF-75 filter paper (Advantec) using a filter aid (Radiolite # 500), and a hollow fiber UF membrane having a molecular weight of 50,000 cut from the culture filtrate from which the cells are removed. The polymer fraction obtained by a membrane filtration apparatus equipped with a module (manufactured by Spectrum) was concentrated, desalted and recovered in a short time, treated with activated carbon, and powdered by freeze drying. The membrane filtration apparatus used was SYLS-SB04 manufactured by Toyobo Engineering.
The polysaccharide fraction obtained in this manner was confirmed by homogeneity using cellulose acetate membrane electrophoresis, and by using DEAE-cellulose ion exchange column chromatographic analysis, chemical analysis, and nuclear magnetic resonance analysis, The mucopolysaccharide was confirmed.
(実施例2)
前培養までは実施例1と同様に処理し、次いでこの前培養液を500ml容の三角フラスコ中に上記組成を有する海水から調製した滅菌培地100ml(121℃、15分間)に接種し、25℃の温度で3日間振とう培養を行った。次いで培養液を遠心分離した後濾過助剤(ラヂオライト#500)を用いてGF−75濾紙(Advantec)で濾過し、菌体を除いた培養濾液から分子量5万カットの中空糸UF膜モジュール(Spectrum社製)を備えた膜濾過装置により得られる高分子画分を短時間のうちに濃縮、脱塩回収し、活性炭処理し、凍結乾燥により粉末化した。膜濾過装置は東洋紡エンジニアリング社製SYLS-SB04型を用いた。このようにして得られた多糖画分については、セルロースアセテート膜電気泳動を用いて均一性を確認すると共に、DEAE-セルロースイオン交換カラムクロマト分析、化学分析、核磁気共鳴分析により、公知の本酸性ムコ多糖類であることを確認した。
(Example 2)
Until the preculture, the same treatment as in Example 1 was performed, and then this preculture was inoculated into a 500 ml Erlenmeyer flask to 100 ml of sterilized medium (121 ° C, 15 minutes) prepared from seawater having the above composition, and 25 ° C. The shaking culture was performed at the temperature of 3 days. Next, after centrifuging the culture solution, it was filtered with GF-75 filter paper (Advantec) using a filter aid (Radiolite # 500), and a hollow fiber UF membrane module having a molecular weight of 50,000 cut from the culture filtrate from which the bacterial cells were removed ( The polymer fraction obtained by a membrane filtration apparatus equipped with Spectrum (trade name) was concentrated, desalted and recovered in a short time, treated with activated carbon, and pulverized by freeze-drying. The membrane filtration apparatus used was SYLS-SB04 manufactured by Toyobo Engineering. The polysaccharide fraction obtained in this manner was confirmed by homogeneity using cellulose acetate membrane electrophoresis, and by using DEAE-cellulose ion exchange column chromatographic analysis, chemical analysis, and nuclear magnetic resonance analysis, The mucopolysaccharide was confirmed.
(実施例3)
前培養までは実施例1と同様に処理し、上記実施例2で述べた培地に寒天を1.5%添加した寒天平板培地250mlを平板(18×26cm)に広げて前培養液を塗沫し、25℃の温度で4日間培養を行った。寒天平板の表面に生じた粘質物をかきとり、1%フェノール液に懸濁させ、遠心分離した後濾過助剤(ラヂオライト#500)を用いてGF-75濾紙で濾過し、菌体を除いた上澄液にエタノールを加えて沈殿する画分を集め、水に溶解後再度エタノールを加えて沈殿する画分を集め、水に溶解後透析した。次いで活性炭処理し、凍結乾燥により多糖画分を得た。尚、実用的な精製レベルとしては、培養濾過液から分子量5万カットの中空糸UF膜モジュール(Spectrum社製)を備えた膜濾過装置により得られる高分子画分を短時間のうちに濃縮、脱塩回収し、活性炭処理し、凍結乾燥により粉末化した。膜濾過装置は東洋紡エンジニアリング社製SYLS-SB04型を用いた。このようにして得られた多糖画分については、セルロースアセテート膜電気泳動を用いて均一性を確認すると共に、DEAE-セルロースイオン交換カラムクロマト分析、化学分析、核磁気共鳴分析により、公知の本酸性ムコ多糖類であることを確認した。
(Example 3)
Until the pre-culture, the same treatment as in Example 1 was performed, and 250 ml of agar plate medium obtained by adding 1.5% of agar to the medium described in Example 2 was spread on a flat plate (18 × 26 cm) and smeared with the pre-culture solution. The culture was performed at a temperature of 25 ° C. for 4 days. The sticky matter generated on the surface of the agar plate is scraped off, suspended in 1% phenol solution, centrifuged, and filtered through GF-75 filter paper using a filter aid (Radiolite # 500) to remove the cells. Fraction precipitated by adding ethanol to the supernatant was collected, dissolved in water, ethanol added again to collect the precipitated fraction, dissolved in water, and dialyzed. Subsequently, it was treated with activated carbon, and a polysaccharide fraction was obtained by freeze-drying. In addition, as a practical purification level, the polymer fraction obtained by a membrane filtration apparatus equipped with a hollow fiber UF membrane module (Spectrum) having a molecular weight of 50,000 cut from the culture filtrate is concentrated in a short time. Desalted and recovered, treated with activated carbon, and powdered by freeze-drying. The membrane filtration apparatus used was SYLS-SB04 manufactured by Toyobo Engineering. The polysaccharide fraction obtained in this manner was confirmed by homogeneity using cellulose acetate membrane electrophoresis, and by using DEAE-cellulose ion exchange column chromatographic analysis, chemical analysis, and nuclear magnetic resonance analysis, The mucopolysaccharide was confirmed.
(実施例4)
(マウス培養細胞株によるメラニン生成抑制試験)
実施例1で得られた本酸性ムコ多糖類を使用して,メラノーマ細胞に対する細胞増殖と美白効果を調べ試料無添加の場合と比較して試料添加系での細胞増殖率,メラニン生成量を求めた。
Example 4
(Inhibition test of melanin production using mouse cell lines)
Using the acidic mucopolysaccharide obtained in Example 1, cell proliferation and whitening effects on melanoma cells were examined, and the cell growth rate and melanin production amount in the sample addition system were determined as compared with the case of no sample addition. It was.
(細胞培養)
(1)前培養したB16F10細胞を12穴マルチウェルプレートの各ウェルに1.0x104細胞/ウェルの細胞数に播種した。播種48時間後、所定濃度の被験物質を含む0.5mMテオフィリン含有DMEM+10%FBS培地に交換した。被験物質の濃度は、25μg/ml、50μg/ml、100μg/mlに設定した。各試料濃度毎に3ウェルを割り当てアッセイに供した(N=3)。細胞増殖計数用のプレートとメラニン定量用のプレート2枚を1組として各試料のアッセイに使用した。培地交換後、72時間培養を続けた。
(2)細胞増殖計数用プレートを用いて各ウェル内の細胞数(相対値)をWST-1法を用い450nmの吸光度を測定することにより、細胞の生育度を測定した。
(Cell culture)
(1) Pre-cultured B16F10 cells were seeded in each well of a 12-well multiwell plate at a cell number of 1.0 × 10 4 cells / well. 48 hours after seeding, the medium was replaced with a DMEM + 10% FBS medium containing 0.5 mM theophylline containing a predetermined concentration of the test substance. The concentration of the test substance was set to 25 μg / ml, 50 μg / ml, and 100 μg / ml. Three wells were assigned for each sample concentration and subjected to the assay (N = 3). A plate for counting cell proliferation and two plates for quantifying melanin were used as a set for assay of each sample. After the medium change, the culture was continued for 72 hours.
(2) The degree of cell growth was measured by measuring the number of cells in each well (relative value) using a cell proliferation counting plate and measuring the absorbance at 450 nm using the WST-1 method.
(細胞中のメラニン量の測定方法)
B-16メラノーマ細胞を培養し、細胞中に産生したメラニンをアルカリで溶解し、吸光度を測定することによりメラニン生成量を求めた。72時間培養後のメラニン定量用のプレートを用いて各ウェル内の細胞を10%トリクロロ酢酸溶液で処理した後にエタノール/エーテル(1:1(V/V))で処理した。
これに1N-NaOH/10%DMSO溶液を加え、メラニンを可溶化した後吸光度475nmを測定した。合成メラニン(Sigma)を1N-NaOH/10%DMSO溶液に溶解した溶液を所定の濃度に希釈し標準液として使用し、本標準液と測定溶液の吸光度を比較することにより測定溶液中のメラニン含有量を算出した。(2)で求めたウェル内細胞数(相対値)と本ウェル内メラニン量から細胞内メラニン量(相対値)を計算した。これらの結果を図1に示す。
(Method for measuring the amount of melanin in cells)
B-16 melanoma cells were cultured, melanin produced in the cells was dissolved in alkali, and the amount of melanin produced was determined by measuring the absorbance. Cells in each well were treated with a 10% trichloroacetic acid solution using a plate for melanin quantification after 72 hours of culture, and then treated with ethanol / ether (1: 1 (V / V)).
1N-NaOH / 10% DMSO solution was added to this to solubilize melanin, and then the absorbance was measured at 475 nm. A solution prepared by dissolving synthetic melanin (Sigma) in 1N-NaOH / 10% DMSO solution is diluted to a predetermined concentration and used as a standard solution. By comparing the absorbance of this standard solution and the measurement solution, the content of melanin in the measurement solution is contained. The amount was calculated. The intracellular melanin amount (relative value) was calculated from the number of cells in the well (relative value) obtained in (2) and the amount of melanin in this well. These results are shown in FIG.
図1から明らかなように,本酸性多糖類の添加によりメラニン生成の抑制が認められた。また本酸性ムコ多糖類は,メラノーマ細胞の増殖抑制効果、すなわち細胞毒性は認められなかった。各濃度の本酸性多糖類の添加で細胞毒性に伴う細胞の形態の変化も見られなかった。即ち、本酸性ムコ多糖類は、細胞の生育に影響を与えない濃度範囲で美白作用を示すことが認められた。 As can be seen from FIG. 1, suppression of melanin production was observed by the addition of the present acidic polysaccharide. In addition, the acidic mucopolysaccharide was not observed to inhibit the proliferation of melanoma cells, ie, cytotoxicity. The addition of the acidic polysaccharide at each concentration did not change the cell morphology associated with cytotoxicity. That is, it was confirmed that the acidic mucopolysaccharide exhibits a whitening action in a concentration range that does not affect cell growth.
本発明に係る美白剤は種々の剤型で使用されるが例示として溶液(例えば、美容液、化粧水など)、クリーム、乳液、石けん、乳化型ファンデーション、浴用剤、錠剤および清涼飲料の処方例を処方例1〜8として説明する。 The whitening agent according to the present invention is used in various dosage forms, but examples include solutions (for example, cosmetic liquids, lotions, etc.), creams, emulsions, soaps, emulsified foundations , bath preparations , tablets, and soft drinks . Will be described as Formulation Examples 1-8 .
(処方例1)
処方例1(美容液)
下記成分により常法でもって美容液を調製した。
Formulation Example 1 (Cosmetic liquid)
A cosmetic solution was prepared by the following method using the following ingredients.
(処方例2)
処方例2(クリーム)
下記成分A、別に成分Bを加温溶解させてそれぞれA液およびB液とし、A液にB液を加えて乳化し、撹拌しながら冷却し、クリームを調製した。
Formulation Example 2 (Cream)
The following component A and component B were heated and dissolved to prepare A solution and B solution, respectively. The B solution was added to the A solution to emulsify, and cooled with stirring to prepare a cream.
(処方例3)
処方例3(乳液)
下記成分A、別に成分Bを加温溶解させてそれぞれA液およびB液とし、A液にB液を加えて乳化し、撹拌しながら冷却し、乳液を調製した。
Formulation Example 3 (Emulsion)
The following component A and component B were heated and dissolved to prepare A solution and B solution, respectively. The B solution was added to the A solution to emulsify, and cooled with stirring to prepare an emulsion.
(処方例4)
処方例4(石けん)
石けん製造の常法により下記成分を混合して石けんを製造した。
Formulation example 4 (soap)
The soap was manufactured by mixing the following components according to a conventional method for manufacturing soap.
(処方例5)
処方例5(乳化型ファンデーション)
下記成分Aを充分に混合粉砕した粉末部Aとし、成分BをB液、成分CをC液とする。C液を加温攪拌後、Aを添加しホモミキサー処理し、さらに加温混合したB液を加えてホモミキサー処理する。攪拌しながら室温まで冷却して乳化型ファンデーションを調製した。
Formulation Example 5 (Emulsification Foundation)
The following component A is sufficiently mixed and pulverized into powder part A, component B is liquid B, and component C is liquid C. After the liquid C is heated and stirred, A is added and homomixed, and the liquid B which has been heated and mixed is added and homomixed. While stirring, the mixture was cooled to room temperature to prepare an emulsified foundation.
(処方例6)
処方例6(浴用剤)
下記成分により常法でもって浴用剤を調製した。
Formulation Example 6 (Bath Agent)
A bath preparation was prepared by the following method using the following components.
(処方例7)
処方例7(錠剤)
下記成分Aをそれぞれ篩過して混合し、次に成分Bを添加して混合した。その後、常法により打錠して、全量が600mgの錠剤を得た。
Formulation Example 7 (tablet)
The following component A was sifted and mixed, and then component B was added and mixed. Thereafter, tableting was performed by a conventional method to obtain a tablet having a total amount of 600 mg.
(処方例8)
処方例8(清涼飲料)
下記成分により常法でもって清涼飲料を調製した。
Formulation example 8 (soft drink)
A soft drink was prepared by the following method using the following components.
なお、本実施例1〜3において用いられた上記のFERM P-21297菌株は、日本国独立行政法人産業技術総合研究所 特許生物寄託センター 〒305−8566 日本国茨城県つくば市東1丁目1番地1中央第6 に寄託し、平成19年5月16日 受託番号FERM P-21297として受託されたものである。 In addition, the above-mentioned FERM P-21297 strain used in Examples 1 to 3 is 1-1-1 Higashi, Tsukuba City, Ibaraki Prefecture, Japan The deposit was made in the center No. 6 and was deposited under the accession number FERM P-21297 on May 16, 2007.
Claims (3)
(上記の構造式において、GlcNAcpはピラノース型N-アセチルグルコサミン残基を、GlcUApはピラノース型グルクロン酸残基を、Gluはグルタミン酸を、DはD型を、LはL型を、nは分子量が5万より大きいことを示す繰り返しの数をそれぞれ表す。) A whitening agent comprising an acidic mucopolysaccharide having a structure represented by the following formula (1) or a physiologically acceptable salt thereof as an active ingredient for suppressing melanin production .
(In the above structural formula, GlcNAcp is a pyranose type N-acetylglucosamine residue, GlcUAp is a pyranose type glucuronic acid residue, Glu is glutamic acid, D is D type, L is L type, and n is molecular weight. Each represents the number of repetitions indicating greater than 50,000.)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012124684A JP6251471B2 (en) | 2012-05-31 | 2012-05-31 | Whitening agent |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012124684A JP6251471B2 (en) | 2012-05-31 | 2012-05-31 | Whitening agent |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013249275A JP2013249275A (en) | 2013-12-12 |
JP6251471B2 true JP6251471B2 (en) | 2017-12-20 |
Family
ID=49848322
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012124684A Active JP6251471B2 (en) | 2012-05-31 | 2012-05-31 | Whitening agent |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6251471B2 (en) |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6279790A (en) * | 1985-09-30 | 1987-04-13 | Toyo Jozo Co Ltd | Production of modified hyaluronic acid |
JPH01272511A (en) * | 1988-04-21 | 1989-10-31 | Tokyo Sankei Kagaku:Kk | Additive for cosmetic |
JPH08301904A (en) * | 1995-05-01 | 1996-11-19 | Teika Corp | Humectant comprising polysaccharide as effective component and cosmetic preparation containing the same |
JP3803260B2 (en) * | 2001-03-23 | 2006-08-02 | 伯東株式会社 | Skin external preparation for whitening |
JP4390259B2 (en) * | 2001-09-06 | 2009-12-24 | 有限会社 シーバイオン | Sulfuric acid polysaccharide, method for producing the same, and substance containing the same as an active ingredient |
JP4431766B2 (en) * | 2002-01-15 | 2010-03-17 | 有限会社 シーバイオン | Production method of polysaccharides |
JP3802011B2 (en) * | 2003-06-16 | 2006-07-26 | 有限会社 シーバイオン | Whitening agent |
JP4889206B2 (en) * | 2004-07-01 | 2012-03-07 | 有限会社 シーバイオン | Macrophage activator having IL-12 production inducing activity |
JP4944412B2 (en) * | 2005-09-09 | 2012-05-30 | 有限会社 シーバイオン | Preadipocyte differentiation inhibitor and method for producing the same |
JP2007089541A (en) * | 2005-09-30 | 2007-04-12 | Ehime Prefecture | Method for regulating enzymatic reaction and device of regulation |
JP5270122B2 (en) * | 2007-01-16 | 2013-08-21 | 株式会社ピカソ美化学研究所 | Acidic mucopolysaccharide-producing microorganism, method for producing acidic mucopolysaccharide, and whitening agent containing acidic mucopolysaccharide as an active ingredient |
JP5303186B2 (en) * | 2007-07-09 | 2013-10-02 | 有限会社 シーバイオン | NOVEL MICROORGANISM AND ITS VARIANTS AND METHOD FOR PRODUCING POLYsaccharideS |
JP2012031089A (en) * | 2010-07-30 | 2012-02-16 | Shiibaion:Kk | Immunostimulator |
JP5953078B2 (en) * | 2012-03-14 | 2016-07-13 | 株式会社ピカソ美化学研究所 | NOVEL MICROORGANISM AND ITS VARIANTS AND METHOD FOR PRODUCING POLYsaccharideS |
-
2012
- 2012-05-31 JP JP2012124684A patent/JP6251471B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP2013249275A (en) | 2013-12-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5270122B2 (en) | Acidic mucopolysaccharide-producing microorganism, method for producing acidic mucopolysaccharide, and whitening agent containing acidic mucopolysaccharide as an active ingredient | |
Anand et al. | Bioactive potential and composition analysis of sulfated polysaccharide from Acanthophora spicifera (Vahl) Borgeson | |
US20080226740A1 (en) | Marine algal extracts comprising marine algal polysaccharides of low degree polymerizaton, and the preparation processes and uses thereof | |
JP5303186B2 (en) | NOVEL MICROORGANISM AND ITS VARIANTS AND METHOD FOR PRODUCING POLYsaccharideS | |
JP6174219B2 (en) | New polysaccharide | |
KR102029078B1 (en) | Novel oligosaccharide compounds and the cosmetic use thereof | |
JP3802011B2 (en) | Whitening agent | |
JP6729913B2 (en) | Anti-inflammatory agent | |
JP2009298738A (en) | External preparation for skin | |
JP6251471B2 (en) | Whitening agent | |
JP6625311B2 (en) | Cosmetics | |
JP2012031089A (en) | Immunostimulator | |
JP4944412B2 (en) | Preadipocyte differentiation inhibitor and method for producing the same | |
JP3806419B2 (en) | Cosmetics | |
JP2003221307A (en) | Agent for inhibiting formation of melanin | |
JP6118519B2 (en) | New polysaccharide | |
JP4390259B2 (en) | Sulfuric acid polysaccharide, method for producing the same, and substance containing the same as an active ingredient | |
JP2009024075A (en) | Polysaccharide, method for producing the same and use of the same | |
JP4889206B2 (en) | Macrophage activator having IL-12 production inducing activity | |
JP2024500509A (en) | Novel Saccharomyces cerevisiae strains and their uses | |
JP6018817B2 (en) | Fat accumulation inhibitor | |
JP2002037742A (en) | Skin care preparation | |
JP2003274928A (en) | Culture medium for producing polysaccharides and method for producing the polysaccharides | |
JP2008120725A (en) | External preparation for skin | |
WO2006090939A1 (en) | Cosmetic composition comprising beta-fructosyl-l-ascorbic acid for skin whitening |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150313 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20151203 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160105 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160129 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20160531 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160722 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160818 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20161028 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20171127 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6251471 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |