JP2005029556A - Skin aging-preventing agent - Google Patents
Skin aging-preventing agent Download PDFInfo
- Publication number
- JP2005029556A JP2005029556A JP2003371317A JP2003371317A JP2005029556A JP 2005029556 A JP2005029556 A JP 2005029556A JP 2003371317 A JP2003371317 A JP 2003371317A JP 2003371317 A JP2003371317 A JP 2003371317A JP 2005029556 A JP2005029556 A JP 2005029556A
- Authority
- JP
- Japan
- Prior art keywords
- hyaluronidase
- skin
- elastase
- extract
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 claims abstract description 53
- 108010003272 Hyaluronate lyase Proteins 0.000 claims abstract description 31
- 102000001974 Hyaluronidases Human genes 0.000 claims abstract description 31
- 229960002773 hyaluronidase Drugs 0.000 claims abstract description 29
- 239000002537 cosmetic Substances 0.000 claims abstract description 28
- 235000013305 food Nutrition 0.000 claims abstract description 28
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 27
- 244000295519 Chimaphila umbellata Species 0.000 claims abstract description 19
- 235000019120 Chimaphila umbellata Nutrition 0.000 claims abstract description 18
- 239000003602 elastase inhibitor Substances 0.000 claims abstract description 17
- 229940122393 Hyaluronidase inhibitor Drugs 0.000 claims abstract description 16
- 229940122858 Elastase inhibitor Drugs 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims description 31
- 239000004480 active ingredient Substances 0.000 claims description 27
- 230000009759 skin aging Effects 0.000 claims description 16
- 241000196324 Embryophyta Species 0.000 claims description 15
- 230000002849 elastaseinhibitory effect Effects 0.000 claims description 13
- 241000332701 Chimaphila Species 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 230000000694 effects Effects 0.000 abstract description 30
- 102000016387 Pancreatic elastase Human genes 0.000 abstract description 12
- 108010067372 Pancreatic elastase Proteins 0.000 abstract description 12
- 239000003795 chemical substances by application Substances 0.000 abstract description 12
- 230000003266 anti-allergic effect Effects 0.000 abstract description 4
- 238000002156 mixing Methods 0.000 abstract description 4
- 235000019135 Chimaphila maculata Nutrition 0.000 abstract description 2
- 235000001620 Chimaphila umbellata subsp acuta Nutrition 0.000 abstract description 2
- 235000001608 Chimaphila umbellata subsp occidentalis Nutrition 0.000 abstract description 2
- 235000001403 Chimaphila umbellata subsp. cisatlantica Nutrition 0.000 abstract description 2
- 239000000284 extract Substances 0.000 description 50
- 210000003491 skin Anatomy 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 11
- 241000195620 Euglena Species 0.000 description 10
- -1 and the like Substances 0.000 description 10
- 239000006210 lotion Substances 0.000 description 10
- 241000221079 Euphorbia <genus> Species 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 230000037303 wrinkles Effects 0.000 description 8
- 230000032683 aging Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 102000016942 Elastin Human genes 0.000 description 6
- 108010014258 Elastin Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 230000003712 anti-aging effect Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 235000009508 confectionery Nutrition 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 229920002549 elastin Polymers 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229920002674 hyaluronan Polymers 0.000 description 6
- 229960003160 hyaluronic acid Drugs 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000037394 skin elasticity Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 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 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 244000025254 Cannabis sativa Species 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 230000001877 deodorizing effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000007654 immersion Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 206010013786 Dry skin Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 240000008620 Fagopyrum esculentum Species 0.000 description 3
- 235000009419 Fagopyrum esculentum Nutrition 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 201000005702 Pertussis Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000008351 acetate buffer Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000013065 commercial product Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000037336 dry skin Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000003779 hair growth Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 235000021056 liquid food Nutrition 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000000419 plant extract Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 210000004761 scalp Anatomy 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 241000254032 Acrididae Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 244000061508 Eriobotrya japonica Species 0.000 description 2
- 235000009008 Eriobotrya japonica Nutrition 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 241000208690 Hamamelis Species 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000123826 Lutjanus campechanus Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010068319 Oropharyngeal pain Diseases 0.000 description 2
- 235000006484 Paeonia officinalis Nutrition 0.000 description 2
- 201000007100 Pharyngitis Diseases 0.000 description 2
- 241000218657 Picea Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000011481 absorbance measurement Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000000118 hair dye Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- 239000008257 shaving cream Substances 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- GVUGADOWXGKRAE-SRVKXCTJSA-N 4-[[(2s)-1-[[(2s)-1-[[(2s)-1-(4-nitroanilino)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 GVUGADOWXGKRAE-SRVKXCTJSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 244000144927 Aloe barbadensis Species 0.000 description 1
- 235000002961 Aloe barbadensis Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241001237961 Amanita rubescens Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 235000006693 Cassia laevigata Nutrition 0.000 description 1
- 244000025596 Cassia laevigata Species 0.000 description 1
- 240000006808 Chimaphila maculata Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 240000009088 Fragaria x ananassa Species 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
- 241000287828 Gallus gallus Species 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
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000736199 Paeonia Species 0.000 description 1
- 244000170916 Paeonia officinalis Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 244000134552 Plantago ovata Species 0.000 description 1
- 235000003421 Plantago ovata Nutrition 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 239000009223 Psyllium Substances 0.000 description 1
- 241001486547 Pyrola japonica Species 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- BQSOOLYKWGLVHV-UHFFFAOYSA-N acetic acid 4-(dimethylamino)benzaldehyde Chemical compound C(C)(=O)O.CN(C1=CC=C(C=O)C=C1)C BQSOOLYKWGLVHV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000003788 bath preparation Substances 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 235000013527 bean curd Nutrition 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax 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
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 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
- 230000020411 cell activation Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 229920002055 compound 48/80 Polymers 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008406 cosmetic ingredient Substances 0.000 description 1
- 235000021438 curry Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000000551 dentifrice Substances 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 235000011850 desserts Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003248 enzyme activator Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 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
- 235000009569 green tea Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000015092 herbal tea Nutrition 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229940014041 hyaluronate Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000005722 itchiness Effects 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 235000021110 pickles Nutrition 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000013324 preserved food Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940070687 psyllium Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 229940124513 senna glycoside Drugs 0.000 description 1
- 230000037393 skin firmness Effects 0.000 description 1
- 230000005808 skin problem Effects 0.000 description 1
- 239000004320 sodium erythorbate Substances 0.000 description 1
- 235000010352 sodium erythorbate Nutrition 0.000 description 1
- RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical compound [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
- 235000021055 solid food Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 235000021012 strawberries Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 235000013618 yogurt Nutrition 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
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Cosmetics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
本発明は、イチヤクソウ科ウメガサソウ属(Chimaphila Pursh)に属する植物であるオオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)を有効成分とする食品組成物、化粧料組成物、医薬組成物などを含む組成物であって、皮膚老化防止剤に関する。
また、本発明は、イチヤクソウ科ウメガサソウ属(Chimaphila Pursh)に属する植物であるオオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)を有効成分とするエラスターゼ阻害剤、ヒアルロニダーゼ阻害剤に関する。また、該阻害剤を含有する食品組成物、化粧料組成物、医薬組成物などを含む組成物であって、皮膚老化防止剤に関し、オオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)の阻害効果を活用した組成物およびその利用分野への使用方法に関する。
さらに、オオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)を有効成分とするエラスターゼ阻害剤、ヒアルロニダーゼ阻害剤の製造方法に関する。
The present invention is a composition comprising a food composition, a cosmetic composition, a pharmaceutical composition, and the like containing, as an active ingredient, Chimophila umbellata (L.) WPCBarton, which is a plant belonging to the genus Chimaphila Pursh. And relates to a skin anti-aging agent.
The present invention also relates to an elastase inhibitor and a hyaluronidase inhibitor containing, as an active ingredient, chimaphila umbellata (L.) WPCBarton, which is a plant belonging to the genus Chimaphila Pursh. Further, it is a composition comprising a food composition, a cosmetic composition, a pharmaceutical composition and the like containing the inhibitor, and relates to a skin aging inhibitor, and has an inhibitory effect on giant pea (Chimaphila umbellata (L.) WPCBarton). The present invention relates to a composition used and a method of using the composition in its application field.
Furthermore, the present invention relates to a method for producing an elastase inhibitor and a hyaluronidase inhibitor, which contains chimaphila umbellata (L.) WPCBarton as an active ingredient.
人の皮膚の老化の代表的な変化はシワやタルミであり、高年齢層や女性にとっては肌の大きな悩みの一つになっている。しかしながら、皮膚のシワやタルミに対する効果的な治療法は現在のところほとんど見当たらないのが現状で、高齢化社会を迎え老化に対する様々な研究が行われている。人の皮膚のシワやタルミの形成には皮膚の弾力低下が原因であると考えられ、その要因としては加齢、乾燥、酸化、太陽光(紫外線)による影響などが関連しているが、具体的な組織学的現象としては、真皮中のエラスチン、コラーゲン、グリコサミノグリカンなどの細胞外マトリックス成分の変化、特にエラスチンの変化が起因していることが挙げられる。つまり、シワやタルミの形成過程で起きる皮膚弾性の減少は、真皮繊維芽細胞より産出分泌されるエラスターゼが、エラスチンの傷害による3次元構造の変性に関わることが考えられ、そのエラスターゼの活性を抑制し、皮膚の弾力やハリを維持するエラスチンの変性防止をすることが、シワやタルミの形成を阻止し、すなわち、皮膚の老化を防止する。 Typical changes in human skin aging are wrinkles and tarmi, which is one of the major skin problems for older people and women. However, at present, there are few effective treatments for skin wrinkles and tarmi, and various studies on aging have been conducted in the aging society. The formation of wrinkles and tarmi on human skin is thought to be caused by a decrease in the elasticity of the skin, and factors such as aging, drying, oxidation, and the effects of sunlight (ultraviolet rays) are related. A typical histological phenomenon is caused by changes in extracellular matrix components such as elastin, collagen, and glycosaminoglycan in the dermis, particularly changes in elastin. In other words, the decrease in skin elasticity that occurs during the formation of wrinkles and tarmi is considered to be due to the elastase produced and secreted from dermal fibroblasts being involved in the modification of the three-dimensional structure caused by elastin injury. However, preventing the degeneration of elastin that maintains the elasticity and firmness of the skin prevents the formation of wrinkles and tarmi, that is, prevents the aging of the skin.
また一方で、皮膚の乾燥、肌荒れ、ハリ、弾力性の低下、シミやシワの増加は、ヒアルロン酸の分解に密接に関わっている。ヒアルロン酸は、皮膚・靭帯・関節液・眼の硝子体などの組織に多く存在するムコ多糖の一種であり、例えば皮膚や口腔においては、細胞の保護・栄養の運搬・組織水分の保持・柔軟性の維持などに、また関節液として組織構造・機能の維持および潤滑性の保持などに重要な役割を果たしている。皮膚や口腔、関節における生体ヒアルロン酸量は、老化または病的状態により減少するため、ヒアルロン酸加水分解酵素であるヒアルロニダーゼを阻害することが、ヒアルロン酸の分解を抑制し、生体ヒアルロン酸量の維持に寄与する。 On the other hand, dry skin, rough skin, firmness, decreased elasticity, and increased spots and wrinkles are closely related to the degradation of hyaluronic acid. Hyaluronic acid is a type of mucopolysaccharide that is abundant in tissues such as skin, ligaments, joint fluid, and vitreous body of the eye. For example, in the skin and oral cavity, it protects cells, transports nutrients, retains tissue moisture, and softens. It plays an important role in maintaining sexuality, as well as maintaining tissue structure and function as a joint fluid and maintaining lubricity. Since the amount of living hyaluronic acid in the skin, oral cavity, and joints decreases due to aging or pathological conditions, inhibiting hyaluronidase, a hyaluronic acid hydrolase, suppresses the degradation of hyaluronic acid and maintains the amount of living hyaluronic acid Contribute to.
さらには、ヒアルロニダーゼ阻害剤はヒアルロニダーゼに起因する抗炎症、抗アレルギー剤にも利用できる。これはヒアルロニダーゼが炎症時に活性化され、結合組織のマトリックスを破壊し、炎症系の組織への浸潤、血管の透過性を亢進すること、I型アレルギーにおける肥満細胞からのヒスタミンの遊離過程に介在している可能性が高いことによる。
エラスターゼ活性阻害について、エラスターゼの過度の作用を抑制することができれば皮膚老化の防止が可能となる。しかしながら、従来報告されているエラスターゼ阻害物質は安定性、効果、使用感の点で、必ずしも満足できるものではなかった。ヒアルロニダーゼ活性阻害についても、抗炎症あるいは抗アレルギー活性を有する原料について種々検索されているが、安全かつ有望なものは未だ得られていない。人の肌に対する安全性の面から天然物で、多年、人が食したりして、安全性の面で保証されており、しかもヒアルロニダーゼ阻害作用が強く、さらに皮膚に対する他の効果も合わせもつ物質が望まれている。
Furthermore, hyaluronidase inhibitors can be used as anti-inflammatory and anti-allergic agents caused by hyaluronidase. This is because hyaluronidase is activated during inflammation, destroys the matrix of connective tissue, infiltrates inflammatory tissues, enhances vascular permeability, and mediates the process of histamine release from mast cells in type I allergy. It is highly likely that
Regarding elastase activity inhibition, skin aging can be prevented if excessive action of elastase can be suppressed. However, conventionally reported elastase inhibitors are not always satisfactory in terms of stability, effect, and feeling of use. As for the inhibition of hyaluronidase activity, various searches have been made for raw materials having anti-inflammatory or anti-allergic activity, but safe and promising materials have not yet been obtained. It is a natural product from the aspect of safety to human skin, a substance that has been eaten by humans for many years and has been guaranteed in terms of safety, has a strong hyaluronidase inhibitory action, and also has other effects on the skin. It is desired.
本発明はエラスターゼ、ヒアルロニダーゼの活性を阻害し、皮膚のハリ、弾力を回復・維持することにより皮膚の老化を防止し、さらに抗炎症、抗アレルギー作用を有することのできる皮膚の老化防止剤を提供することを目的とする。 The present invention provides an anti-aging agent for skin that inhibits the activity of elastase and hyaluronidase, prevents skin aging by restoring and maintaining the elasticity and elasticity of the skin, and further has anti-inflammatory and anti-allergic effects. The purpose is to do.
本発明者らは、上記課題を解決すべく鋭意研究を重ねた結果、極めて有効でかつ効果的な皮膚の老化防止方法を提供することが可能となり、イチヤクソウ科ウメガサソウ属(Chimaphila Pursh)に属する植物で、例えばオオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)を使用することにより、安全でかつ効率よくエラスターゼ、ヒアルロニダーゼの阻害方法を含む皮膚老化防止方法を見い出た。化粧品分野、医薬分野、食品分野などに極めて有効な本発明を完成するに至った。 As a result of intensive studies to solve the above problems, the present inventors can provide an extremely effective and effective method for preventing skin aging, and a plant belonging to the genus Chimaphila Pursh. Thus, a method for preventing skin aging including a method for inhibiting elastase and hyaluronidase has been found to be safe and efficient by using, for example, Chimaphila umbellata (L.) WPCBarton. The present invention has been completed which is extremely effective in the cosmetics field, pharmaceutical field, food field and the like.
本発明は、イチヤクソウ科ウメガサソウ属(Chimaphila Pursh)に属する植物であり、例えばオオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)の抽出物を有効成分とする食品組成物、化粧料組成物、医薬組成物などを含む組成物を提供する。
また、本発明は、イチヤクソウ科ウメガサソウ属(Chimaphila Pursh)に属する植物であり、例えばオオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)を有効成分とするエラスターゼ阻害剤、ヒアルロニダーゼ阻害剤などを含む皮膚老化防止剤を提供する。また、該阻害剤を含有する食品組成物、化粧料組成物、医薬組成物などを含む組成物に関し、オオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)の該阻害効果を活用した組成物およびその利用分野への使用方法を提供する。例えば、該阻害効果を活用した皮膚の老化防止剤、該皮膚の老化防止剤を含む化粧料組成物を提供し、該皮膚の老化防止効果を利用した老化防止方法も提供する。
The present invention is a plant belonging to the genus Chimaphila Pursh, for example, a food composition, a cosmetic composition, and a pharmaceutical composition containing, as an active ingredient, an extract of Chimaphila umbellata (L.) WPCBarton. And the like.
In addition, the present invention is a plant belonging to the genus Chimaphila Pursh, for example, skin aging prevention containing elastase inhibitor, hyaluronidase inhibitor, etc., which comprises chimophila umbellata (L.) WPCBarton as an active ingredient Provide the agent. The present invention also relates to a composition containing the inhibitor, including a food composition, a cosmetic composition, a pharmaceutical composition, and the like, and a composition utilizing the inhibitory effect of chimaphila umbellata (L.) WPCBarton and use thereof Provide usage in the field. For example, a skin anti-aging agent utilizing the inhibitory effect, a cosmetic composition containing the skin anti-aging agent, and an anti-aging method utilizing the skin anti-aging effect are also provided.
さらに、オオウメガサソウ(Chimaphila umbellata (L.) W.P.C.Barton)を有効成分とするエラスターゼ阻害剤、ヒアルロニダーゼ阻害剤の製造方法を提供する。
本発明の皮膚老化防止とは、老化に伴う象徴的な外観の変化である皮膚のシワ、タルミの形成を阻止し、皮膚にハリやツヤの低下を防止する効果を少なくとも奏することが挙げられる。皮膚老化を防止する方法として、エラスターゼ阻害剤、ヒアルロニダーゼ阻害剤を含み、乾燥から肌を守り、硬くなった角層を柔軟にするための保湿剤、角層重層化を防止する角層重層化防止剤、表皮の機能低下に対して細胞賦活成分とターンオーバーコントロール成分、バリア機能の低下に対してバリア機能回復剤、エラスチンやコラーゲンを生成する線維芽細胞の機能低下を防止する細胞賦活剤、コラーゲンの産出促進を促し、分解酵素コラゲナーゼの活性を抑制するコラーゲン合成促進剤やコラゲナーゼ活性抑制剤、血行を促進する血行促進剤、加齢による真皮乳頭層の平坦化を防止するための基底膜周辺のマトリックス成分の保護剤を用いる方法などがあげられる。
Furthermore, the present invention provides a method for producing an elastase inhibitor and a hyaluronidase inhibitor containing chimaphila umbellata (L.) WPCBarton as an active ingredient.
The prevention of skin aging according to the present invention includes at least the effect of preventing the formation of skin wrinkles and talmi, which are symbolic changes in appearance accompanying aging, and preventing the skin from being reduced in firmness and gloss. As a method to prevent skin aging, it contains an elastase inhibitor and hyaluronidase inhibitor, protects the skin from dryness, moisturizes to soften the hardened stratum corneum, and prevents stratum corneum stratification. Agents, cell activation components and turnover control components for reduced epidermal function, barrier function recovery agents for reduced barrier function, cell activators to prevent elastin and collagen producing fibroblasts, collagen Collagen synthesis promoters and collagenase activity inhibitors that suppress the activity of the degrading enzyme collagenase, blood circulation promoters that promote blood circulation, and around the basement membrane to prevent flattening of the dermal papillary layer due to aging Examples thereof include a method using a protective agent for the matrix component.
本発明のイチヤクソウ科ウメガサソウ属(Chimaphila Pursh)に属する植物としては、オオウメガサソウ、ウメガサソウ等が挙げられる。
本発明のオオウメガサソウは、(PIPSISSEWA) Chimaphila umbellata (L.) W.P.C.Bartonであり、イチヤクソウ科の植物で海岸に近い乾燥した林中に自生する多年生の草本である。北アメリカ、ヨーロッパ、シベリアなどの温帯に産し、日本では茨城県以北に分布している。本発明のオオウメガサソウは、アメリカにおいては古くからハーブティーやキャンディの香料として使用され、ヒトに対して長年使用されていることにより安全性の高い植物である。
本発明のオオウメガサソウは、全草または葉、茎、根、種子などのいずれかを用いることができる。該オオウメガサソウをそのまま用いてもよいし、例えば乾燥した後、粉砕して粉末状にして用いることもできる。
Examples of the plant belonging to the genus Chimaphila Pursh of the present invention include giant scorpion and sage.
The giant crape of the present invention is (PIPSISSEWA) Chimaphila umbellata (L.) WPCBarton, which is a perennial herb that grows naturally in a dry forest near the seashore. It originates in temperate zones such as North America, Europe and Siberia, and is distributed north of Ibaraki Prefecture in Japan. The giant buckwheat of the present invention has long been used as a fragrance for herbal tea and candy in the United States, and is a highly safe plant because it has been used for many years on humans.
Any of the whole grass or leaves, stems, roots, seeds and the like can be used for the giant grasshopper of the present invention. The Euglena can be used as it is, or, for example, after drying, it can be pulverized and used as a powder.
本発明のオオウメガサソウの抽出方法は、上記のオオウメガサソウを、エラスターゼ阻害効果および/またはヒアルロニダーゼ阻害効果を消失しない条件で抽出すればよい。例えば、抽出溶媒としては、水、メチルアルコール、エチルアルコールなどの低級アルコール、或いはプロピレングリコール、1,3-ブチレングリコールなどの多価アルコールなどのアルコール類、アセトンなどのケトン類、ジエチルエーテル、ジオキサン、アセトニトリル、酢酸エチルエステルなどのエステル類、キシレン、ベンゼン、クロロホルムなどが挙げられる。これら溶媒を単独であるいは2種以上の混合溶媒を用いて抽出する。また、抽出残渣から再度抽出する場合には、同一の溶媒に限らず他の溶媒を使用してもよい。本発明のオオウメガサソウと溶剤の比率は、特に限定されるものではないが、オオウメガサソウ全草1重量部に対して溶剤1〜1,000重量部、特に抽出操作、効率の点で5〜100重量部が好ましい。抽出温度は、室温から常圧下での溶剤沸点の範囲が好ましい。抽出操作法としては一般的な方法が採用可能であり、例えば、浸漬法や向流抽出法などでよく、必要に応じて攪拌を併用してもよい。抽出混合物から固形物を分離し抽出液を得ることができる。前記の工程により得た本発明のオオウメガサソウ抽出液である抽出液、その濃縮物を得ることができる。さらに、必要に応じて、分配あるいは各種クロマトグラフィーによる精製や活性炭などによる脱色などの処理を加えてもよい。脱臭操作として、一般的な方法である活性炭による吸着法、水蒸気蒸留法、水溶液の濃縮による脱臭法、二酸化炭素を用いた超臨界流体抽出法、有機溶媒との分配法などが採用できる。また、噴霧乾燥、凍結乾燥などの乾燥工程、常圧、減圧、膜などの濃縮工程、あるいは希釈などを、本発明のオオウメガサソウ抽出液の用途に応じて、任意に必要に応じて調整することができる。 In the method for extracting Euglena serrata according to the present invention, the above-mentioned Euglena can be extracted under conditions that do not lose the elastase inhibitory effect and / or the hyaluronidase inhibitory effect. For example, the extraction solvent includes water, lower alcohols such as methyl alcohol and ethyl alcohol, alcohols such as propylene glycol and polyhydric alcohols such as 1,3-butylene glycol, ketones such as acetone, diethyl ether, dioxane, Examples thereof include esters such as acetonitrile and ethyl acetate, xylene, benzene and chloroform. These solvents are extracted alone or using two or more mixed solvents. Moreover, when extracting again from an extraction residue, you may use not only the same solvent but another solvent. The ratio between the persica and the solvent of the present invention is not particularly limited, but it is 1 to 1,000 parts by weight of the solvent, particularly 5 to 100 in terms of extraction operation and efficiency, with respect to 1 part by weight of the persian grass. Part by weight is preferred. The extraction temperature is preferably in the range of room temperature to the boiling point of the solvent under normal pressure. As the extraction operation method, a general method can be employed. For example, an immersion method or a countercurrent extraction method may be used, and stirring may be used in combination as necessary. A solid can be separated from the extraction mixture to obtain an extract. The extract and the concentrate which are the Euglena extract of the present invention obtained by the above-mentioned process can be obtained. Furthermore, if necessary, a treatment such as partitioning or purification by various chromatography or decolorization with activated carbon may be added. As a deodorizing operation, an adsorption method using activated carbon, a steam distillation method, a deodorizing method by concentrating an aqueous solution, a supercritical fluid extraction method using carbon dioxide, a method of partitioning with an organic solvent, or the like can be employed. In addition, drying processes such as spray drying and freeze-drying, normal pressure, reduced pressure, concentration processes such as membranes, dilution, etc., may be arbitrarily adjusted as necessary according to the use of the extract of the perennial extract. Can do.
本発明のオオウメガサソウ抽出物を有効成分とするエラスターゼ阻害剤は、少なくとも上記のオオウメガサソウ抽出物を含有すればよく、目的とするエラスターゼ阻害効果を有し、エラスターゼ活性によるエラスチンの傷害に起因するシワ、タルミなどの皮膚弾性の減少、皮膚老化などを予防、防止または低下し、例えば化粧料組成物としての商品価値を向上するものである。本発明の該エラスターゼ阻害剤は、該オオウメガサソウ抽出物を溶液または粉末形態として製剤化することができ、あるいは添加対象とする製品の性状や工程などに合せて、顆粒状やペースト状の最も効果が期待できる剤型に加工することができる。また、本発明の該エラスターゼ阻害剤は、前記のオオウメガサソウ抽出物と他の成分との混合形態であってもよい。そのような成分としては、オオウメガサソウ抽出物の効果を損なわないものであって、かつ食品組成物、化粧料組成物、医薬組成物の加工やその機能などに好ましい効果を有するものを使用することができる。さらに、本発明のエラスターゼ阻害剤の有効成分である該オオウメガサソウ抽出物は、目的とする効果、使用方法から添加量、濃度を算出し使用すればよい。 The elastase inhibitor containing the Euglena extract of the present invention as an active ingredient only needs to contain at least the above-mentioned extract of Euphorbia, has the intended elastase inhibitory effect, and is a wrinkle caused by elastin injury due to elastase activity. It prevents, prevents or reduces skin elasticity such as talmi, skin aging, etc., and improves the commercial value of a cosmetic composition, for example. The elastase inhibitor of the present invention can be formulated into a solution or a powder form of the extract of Euphorbia or the most effective in the form of granules or paste according to the properties and processes of the product to be added. Can be processed into a dosage form that can be expected. In addition, the elastase inhibitor of the present invention may be in the form of a mixture of the above-mentioned extract of pertussis and other components. As such a component, one that does not impair the effect of the extract of persica and has a favorable effect on the processing and function of food composition, cosmetic composition, pharmaceutical composition, etc. should be used. Can do. Further, the Euglena spruce extract, which is an active ingredient of the elastase inhibitor of the present invention, may be used by calculating the addition amount and concentration from the intended effect and usage method.
本発明のオオウメガサソウ抽出物を有効成分とするヒアルロニダーゼ阻害剤は、少なくとも上記のオオウメガサソウ抽出物を含有すればよく、目的とするヒアルロニダーゼ阻害効果を有し、ヒアルロニダーゼ活性に起因する皮膚老化、抗炎症などを予防、防止または低下し、例えば化粧料組成物としての商品価値を向上するものである。本発明の該ヒアルロニダーゼ阻害剤は、該オオウメガサソウ抽出物を溶液または粉末形態として製剤化することができ、あるいは添加対象とする製品の性状や工程などに合せて、顆粒状やペースト状の最も効果が期待できる剤型に加工することができる。また、本発明の該ヒアルロニダーゼ阻害剤は、前記のオオウメガサソウ抽出物と他の成分との混合形態であってもよい。そのような成分としては、オオウメガサソウ抽出物の効果を損なわないものであって、かつ食品組成物、化粧料組成物、医薬組成物の加工やその機能などに好ましい効果を有するものを使用することができる。さらに、本発明のヒアルロニダーゼ阻害剤の有効成分である該オオウメガサソウ抽出物は、目的とする効果、使用方法から添加量、濃度を算出し使用すればよい。 The hyaluronidase inhibitor containing the perennial extract of the present invention as an active ingredient only needs to contain at least the above-described extract of pertussis and has the intended hyaluronidase inhibitory effect, and skin aging and anti-inflammation caused by hyaluronidase activity Are prevented, prevented or reduced, and for example, the commercial value as a cosmetic composition is improved. The hyaluronidase inhibitor of the present invention can be formulated as a solution or a powder form of the extract of Psyllium or the most effective in the form of granules or paste according to the properties and processes of the product to be added. Can be processed into a dosage form that can be expected. In addition, the hyaluronidase inhibitor of the present invention may be in the form of a mixture of the above-mentioned extract of pertussis and other components. As such a component, one that does not impair the effect of the extract of persica and has a favorable effect on the processing and function of food composition, cosmetic composition, pharmaceutical composition, etc. should be used. Can do. Furthermore, the extract of Euglena serrata, which is an active ingredient of the hyaluronidase inhibitor of the present invention, may be used by calculating the addition amount and concentration from the intended effect and usage method.
本発明の化粧料組成物は、本発明のオオウメガサソウを有効成分とする化粧料組成物(医薬部外品を含む)である。さらには、オオウメガサソウを有効成分とし、エラスターゼ阻害効果および/またはヒアルロニダーゼ阻害効果を奏する化粧料組成物である。本発明の化粧料組成物の剤型は任意であり、カプセル状、顆粒状、粉末状、固形状、液状、ゲル状、気泡状、乳液状、クリーム状、軟膏状、シート状などの化粧品類、医薬部外品類、皮膚・頭髪用化粧品類に配合して用いることができる。具体的には、例えば、外用薬用製剤、化粧水、クリーム、軟膏、乳液、ローション、オイル、パックなどの基礎化粧料、洗顔料や皮膚洗浄料、マッサージ用剤、クレンジング用剤、アフターシェーブローション、プレショーブローション、シェービングクリーム、シャンプー、リンス、ヘヤートリートメント、整髪料、パーマ剤、ヘアートニック、染毛料、育毛・養毛料などの頭髪/頭皮化粧料、ファンデーション、口紅、頬紅、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、香水類、浴用剤、その他歯磨類、口中清涼剤、消臭・防腐剤、衛生綿類、ウエットティッシュなど様々な製品に応用できる。 The cosmetic composition of the present invention is a cosmetic composition (including quasi-drugs) containing the giant megakosa of the present invention as an active ingredient. Furthermore, it is a cosmetic composition that has Euphorbia as an active ingredient and exhibits an elastase inhibitory effect and / or a hyaluronidase inhibitory effect. The dosage form of the cosmetic composition of the present invention is arbitrary, and cosmetics such as capsules, granules, powders, solids, liquids, gels, bubbles, emulsions, creams, ointments, sheets, etc. It can be used in combination with quasi drugs and cosmetics for skin and hair. Specifically, for example, external pharmaceutical preparations, lotions, creams, ointments, emulsions, lotions, oils, packs, and other basic cosmetics, facial cleansers and skin cleansing agents, massage agents, cleansing agents, aftershave lotions, pre-shows Hair lotion, shaving cream, shampoo, rinse, hair treatment, hair conditioner, perm, hair nick, hair dye, hair growth / hair restoration, etc., foundation, lipstick, blusher, eye shadow, eyeliner, mascara It can be applied to various products such as make-up cosmetics, perfumes, bath preparations, other dentifrices, mouth fresheners, deodorants / preservatives, sanitary cotton, and wet tissues.
本発明の化粧料組成物の製造方法は、植物油などの油脂類、ラノリンやミツロウなどのロウ類、ボタンピ、キダチアロエ、センナなどの植物抽出物、炭化水素類、脂肪酸、高級アルコール類、エステル類、種々の界面活性剤、色素、香料、ビタミン類、動物抽出物、紫外線吸収剤、抗酸化剤、防腐・殺菌剤など、通常の化粧料原料として使用されているものを適宜配合して製造することができるし、さらに一般にエラスターゼ阻害剤および/またはヒアルロニダーゼ阻害剤として既知である他の植物抽出物などを併用することで、効果を高めることもできる。本発明のオオウメガサソウの配合量は、その剤型などを考慮して定めることが好ましいが、一般的には全量に対して0.001〜50重量%、好ましくは、0.01〜20重量%程度とすればよい。 The method for producing the cosmetic composition of the present invention includes oils and fats such as vegetable oils, waxes such as lanolin and beeswax, plant extracts such as button pi, yellow aloe vera and senna, hydrocarbons, fatty acids, higher alcohols, esters, Various surfactants, pigments, fragrances, vitamins, animal extracts, UV absorbers, antioxidants, antiseptics, bactericides, and other ingredients that are used as normal cosmetic ingredients are appropriately blended and manufactured. The effect can also be enhanced by using in combination with other plant extracts generally known as elastase inhibitors and / or hyaluronidase inhibitors. It is preferable to determine the blending amount of the giant buckwheat of the present invention in consideration of its dosage form, etc., but generally 0.001 to 50% by weight, preferably 0.01 to 20% by weight based on the total amount It should be about.
本発明の食品組成物は、本発明のオオウメガサソウを有効成分とする食品組成物である。さらには、オオウメガサソウを有効成分とし、エラスターゼ阻害効果および/またはヒアルロニダーゼ阻害効果を奏する食品組成物である。各種の加工食品が挙げられ、そのままの形態でも喫食が可能である食品が好ましい。例えば、液状食品、固形食品、粉末、抽出エキス、ペースト、乾燥食品などの各種飲食物が挙げられる。その代表例としては、各種飲料類として、野菜飲料、果実飲料、乳飲料、酒類などが、各種菓子類として、クッキー、ビスケット、チョコレート、飴、チューインガム、キャンデー、ゼリーなどが、各種乳製品として、ヨーグルト、チーズなどが、各種冷菓として、アイスクリームなどが、各種畜肉製品として、ハム、ソーセージなどが例示できる。さらに、各種の調味料、スープ、カレー、めん類、パン類、漬物類、シリアル、豆腐類、ふりかけ類、ドリンク類などを例示できる。しかし、前記例示により本発明のエラスターゼ阻害効果および/またはヒアルロニダーゼ阻害剤の取り得る形態が限定されるものではない。 The food composition of the present invention is a food composition containing the giant megakosa of the present invention as an active ingredient. Further, the present invention provides a food composition that has Euphorbia as an active ingredient and exhibits an elastase inhibitory effect and / or a hyaluronidase inhibitory effect. Various kinds of processed foods can be mentioned, and foods that can be eaten as they are are preferred. For example, various foods and drinks such as liquid food, solid food, powder, extract extract, paste, and dried food are included. As typical examples, as various beverages, vegetable beverages, fruit beverages, milk beverages, alcoholic beverages, etc., as various confectionery items, cookies, biscuits, chocolate, strawberries, chewing gum, candy, jelly, etc., as various dairy products, Yogurt, cheese and the like can be exemplified as various frozen desserts, ice cream and the like, and various livestock products can be exemplified by ham and sausage. Furthermore, various seasonings, soup, curry, noodles, breads, pickles, cereals, tofu, sprinkles, drinks and the like can be exemplified. However, the above examples are not intended to limit the elastase inhibitory effect and / or the form of the hyaluronidase inhibitor of the present invention.
本発明の食品組成物の製造方法は、既知の方法のいずれかによって行うことができる。本発明のオオウメガサソウを有効成分とする食品の形態としては、通常の食品形態の他、カプセルなどの錠剤食、濃厚流動食、自然流動食、半消化体栄養食、成分栄養食、ドリンク栄養食などの経口経腸栄養食品、機能性食品などがあげられる。本発明の食品組成物には、さらにブドウ糖、果糖、ショ糖、マルトース、ソルビトール、ステビア抽出物、甘草抽出物、コーンシロップ、乳糖、クエン酸、酒石酸、リンゴ酸、コハク酸、乳酸、L-アスコルビン酸、dl-α-トコフェノール、エリソルビン酸ナトリウム、グリセリン、プロピレングリコール、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ショ糖脂肪酸エステル、ソルビタン脂肪酸エステル、プロピレングリコール脂肪酸エステル、アラビアガム、カラギーナン、カゼイン、ゼラチン、ペクチン、寒天、ビタミンB類、パントテン酸カルシウム、アミノ酸類、カルシウム塩類、色素、香料、保存剤など、通常の食品原料として使用されているものを適宜配合して製造することができるし、さらに一般にエラスターゼ阻害効果および/またはヒアルロニダーゼ阻害効果が既知である他の植物抽出物などを併用することで、効果を高めることもできる。本発明のオオウメガサソウの配合量は、その剤型などを考慮して定めることが好ましいが、一般的には全量に対して0.001〜50重量%、好ましくは、0.01〜20重量%程度とすればよい。 The method for producing a food composition of the present invention can be performed by any known method. As the form of the food containing the persica as the active ingredient of the present invention, in addition to the normal food form, tablet food such as capsules, concentrated liquid food, natural liquid food, semi-digested nutrition food, ingredient nutrition food, drink nutrition food Oral enteral nutritional foods, functional foods and the like. The food composition of the present invention further includes glucose, fructose, sucrose, maltose, sorbitol, stevia extract, licorice extract, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbine Acid, dl-α-tocophenol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan, casein, gelatin, Pectin, agar, vitamin Bs, calcium pantothenate, amino acids, calcium salts, pigments, fragrances, preservatives, etc. can be prepared by appropriately blending those used as usual food ingredients, and more generally Elasta By peptidase inhibitory effect and / or hyaluronidase inhibitory effect in combination such as other plant extracts known, it is also possible to enhance the effect. It is preferable to determine the blending amount of the giant buckwheat of the present invention in consideration of its dosage form, etc., but generally 0.001 to 50% by weight, preferably 0.01 to 20% by weight based on the total amount It should be about.
本発明のオオウメガサソウを有効成分とするエラスターゼ阻害効果および/またはヒアルロニダーゼ阻害効果を奏する酵素阻害効果を用いた方法は、オオウメガサソウを含む組成物および方法であり、例えば、蛋白質や細胞を含む組成物、食品組成物、化粧料組成物、医薬組成物が挙げられ、該酵素阻害効果を奏する方法であれば、これらに限定されない。本発明の有効成分である上記オオウメガサソウが、ヒアルロニダーゼ、エラスターゼ阻害活性を有することにより、皮膚のハリや弾力を保持する効果に優れている。また、優れたヒアルロニダーゼ阻害作用により、ヒアルロニダーゼに起因する炎症やアレルギーの予防・治療に有効である。該利用分野は、例えば、動物用製剤も含む各種の外用製剤類全般において利用でき、具体的には、アンプル状、カプセル状、丸剤状、錠剤状、粉末状、顆粒状、固形状、液状、ゲル状または気泡状の1)医薬品類、2)医薬部外品類、3)局所用または全身用の皮膚用化粧品類(例えば、化粧水、乳液、クリーム、軟膏、ローション、オイル、パックなどの基礎化粧料、洗顔料や皮膚洗浄料、マッサージ用剤、クレンジング用剤、除毛剤、脱毛剤、髭剃り処理料、アフターシェーブローション、プレショーブローション、シェービングクリームなど)、4)頭皮・頭髪に適用する薬用または/および化粧用の製剤類(例えば、シャンプー剤、リンス剤、トリートメント剤、パーマネント剤、染毛料、整髪料、ヘアートニック剤、育毛・養毛料など)、5)浴湯に投じて使用する浴用剤、6)その他、消臭・防臭剤や衛生用品、衛生綿類、ウエットテッシュなどが挙げられる。また、一般食品組成物への利用も可能である。 The method using the enzyme inhibitory effect having the elastase inhibitory effect and / or the hyaluronidase inhibitory effect comprising the giant red snapper as an active ingredient is a composition and method containing the giant red snapper, for example, a composition containing a protein or a cell. , Food compositions, cosmetic compositions, and pharmaceutical compositions, and any method that exhibits the enzyme inhibitory effect is not limited thereto. The above-mentioned giant megasas which is an active ingredient of the present invention has hyaluronidase and elastase inhibitory activity, and thus is excellent in the effect of retaining skin elasticity and elasticity. In addition, the superior hyaluronidase inhibitory action is effective in preventing and treating inflammation and allergies caused by hyaluronidase. The field of application can be used in various external preparations including animal preparations, and specifically, ampoules, capsules, pills, tablets, powders, granules, solids, liquids Gels or foams 1) Pharmaceuticals, 2) Quasi-drugs, 3) Topical or systemic skin cosmetics (eg lotions, emulsions, creams, ointments, lotions, oils, packs, etc.) Basic cosmetics, facial cleansers and skin cleansers, massage agents, cleansing agents, depilators, depilators, shaving treatments, after shave lotion, pre-show broth, shaving cream, etc.) 4) Applicable to scalp and hair Medicinal or / and cosmetic preparations (for example, shampoos, rinses, treatments, permanents, hair dyes, hair styling, hair stylings, hair growth / hair growth 5) Bathing agents used in bath water, 6) In addition, deodorizing / deodorizing agents, sanitary products, sanitary cotton, wet tissue, and the like. Moreover, the utilization to a general food composition is also possible.
本発明の有効成分である上記オオウメガサソウが、ヒアルロニダーゼ、エラスターゼ阻害活性を有することにより、皮膚のハリや弾力を保持する効果に優れ、かつ植物由来で安全である。また、優れたヒアルロニダーゼ阻害作用により、ヒアルロニダーゼに起因する炎症やアレルギーの予防・治療に有効であり、食品組成物、医薬組成物並びに化粧品分野の各種の化粧料組成物への応用も可能である。
また、本発明のオオウメガサソウが属するイチヤクソウ科ウメガサソウ属の植物は、イチヤクソウが属するイチヤクソウ科イチヤクソウ属の植物と比較して、エラスターゼ阻害作用等が優れており、より高い皮膚老化防止効果を奏する。
以下、実施例によって本発明を具体的に説明するが、本発明は、以下の実施例によって限定されるものではない。
The above-mentioned Euglena as an active ingredient of the present invention has hyaluronidase and elastase inhibitory activity, so that it is excellent in the effect of retaining skin elasticity and elasticity, and is safe from plants. In addition, it has an excellent inhibitory action on hyaluronidase, and is effective in preventing and treating inflammation and allergies caused by hyaluronidase, and can be applied to food compositions, pharmaceutical compositions, and various cosmetic compositions in the cosmetic field.
In addition, the plant belonging to the genus Umegasausaceae to which the Euphorbia genus of the present invention belongs has superior elastase inhibitory action and the like, and has a higher skin aging prevention effect than the plants of the genus Ichyakusaceae to which Ichiakuso belongs.
EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention is not limited by a following example.
オオウメガサソウ全草100gに、精製水1,000mlを加え、室温で30分間浸漬抽出した後、吸引濾過し、オオウメガサソウの抽出液を得た。これを減圧濃縮乾固し、60℃で12時間以上加熱乾燥することにより、11.5gのオオウメガサソウ抽出物の粉末を得た。 Purified water (1,000 ml) was added to 100 g of persian grass and extracted by immersion for 30 minutes at room temperature, followed by suction filtration to obtain an extract of Scotsweed. This was concentrated to dryness under reduced pressure, and heated and dried at 60 ° C. for 12 hours or longer to obtain 11.5 g of a powder of the extract of persica.
オオウメガサソウ全草100gに、50%エチルアルコール1,000mlを加え、室温で1時間浸漬抽出した後、吸引濾過し、オオウメガサソウの抽出液を得た。これを減圧濃縮乾固して、60℃で12時間以上加熱乾燥することにより、12.1gのオオウメガサソウ抽出物の粉末を得た。 After adding 1,000 ml of 50% ethyl alcohol to 100 g of the whole grass, it was subjected to immersion extraction at room temperature for 1 hour, followed by suction filtration to obtain an extract of Euphorbia. This was concentrated to dryness under reduced pressure, and heated and dried at 60 ° C. for 12 hours or longer to obtain 12.1 g of Cyprus extract.
オオウメガサソウ葉100gに、50%エチルアルコール1,000mlを加え、室温で4時間浸漬抽出した後、吸引濾過し、オオウメガサソウの抽出液を得た。これを減圧濃縮乾固して、60℃で12時間以上加熱乾燥することにより、13.4gのオオウメガサソウ抽出物の粉末を得た。 After adding 1,000 ml of 50% ethyl alcohol to 100 g of persian leaves, it was subjected to immersion extraction at room temperature for 4 hours, followed by suction filtration to obtain an extract of persica. This was concentrated to dryness under reduced pressure, and heated and dried at 60 ° C. for 12 hours or longer to obtain 13.4 g of a powder of the extract of Cyprus persica.
〈エラスターゼ阻害活性の測定〉
エラスターゼ阻害作用は、ブタ膵臓由来エラスターゼ(和光純薬社製)および合成基質スクシニル-L-アラニル-L-アラニル-L-アラニン-p-ニトロアニリド)(ナカライテスク社製)を用いて評価した。基質をジメチルスルホキシドで0.1Mに調整し、使用時に、0.2M Tris-HCl緩衝液(pH8.8)で100倍希釈した1mM溶液を使用した。酵素は0.2M Tris-HCl緩衝液(pH8.8)で0.05unit/mlに調製した。基質100μlを酵素50μlおよび試料50μlとともに37℃で30分間反応させ、その後、吸光度405nmで測定した。試料は実施例2及び3で得られたものを0.2M Tris-HCl緩衝液(pH8.8)で0.1%濃度に調製し使用した。上記と同様の酵素反応と吸光度測定を、試料溶液の代わりに緩衝液を添加して行った。さらにそれぞれの場合について酵素を添加せずに緩衝液を加えて同様の操作と測定を行った。以下の数1により阻害率を算出し、上述の測定結果を表1に示した。対照として、エラスターゼに対する阻害活性を持つ事が知られているイチヤクソウ抽出物(以下の作成方法により製造)、ビワ葉抽出物(市販品)、ハマメリス抽出物(市販品) 、シャクヤク抽出物(市販品)を試験に用いた。
なお、イチヤクソウ科イチヤクソウ属イチヤクソウ(Pyrola japonica klenze ex Alef)に関し、全草100gに、50%エタノール1,000mlを加え、室温で1時間浸漬抽出した後、吸引濾過し、該イチヤクソウの抽出液を得た。これを減圧濃縮乾固して、60℃で12時間以上加熱乾燥することによりイチヤクソウ抽出物の粉末を得た。
<Measurement of elastase inhibitory activity>
The elastase inhibitory action was evaluated using porcine pancreatic elastase (manufactured by Wako Pure Chemical Industries) and the synthetic substrate succinyl-L-alanyl-L-alanyl-L-alanine-p-nitroanilide (manufactured by Nacalai Tesque). The substrate was adjusted to 0.1 M with dimethyl sulfoxide, and a 1 mM solution diluted 100-fold with 0.2 M Tris-HCl buffer (pH 8.8) was used at the time of use. The enzyme was adjusted to 0.05 unit / ml with 0.2 M Tris-HCl buffer (pH 8.8). 100 μl of substrate was reacted with 50 μl of enzyme and 50 μl of sample at 37 ° C. for 30 minutes, and then the absorbance was measured at 405 nm. Samples obtained in Examples 2 and 3 were prepared with a 0.2M Tris-HCl buffer (pH 8.8) to a concentration of 0.1% and used. The same enzyme reaction and absorbance measurement as described above were performed by adding a buffer solution instead of the sample solution. Further, in each case, the same operation and measurement were performed by adding a buffer solution without adding an enzyme. The inhibition rate was calculated by the following formula 1, and the above measurement results are shown in Table 1. As controls, yew extract, which is known to have inhibitory activity against elastase (produced by the following preparation method), loquat leaf extract (commercial product), hamamelis extract (commercial product), peonies extract (commercial product) ) Was used in the test.
For Pyrola japonica klenze ex Alef, add 1,000 ml of 50% ethanol to 100 g of whole plant, soak and extract at room temperature for 1 hour, and then suction filter to obtain the extract of Ichyakus It was. This was concentrated to dryness under reduced pressure, and dried by heating at 60 ° C. for 12 hours or more to obtain a powder of Ichiyaku extract.
〈ヒアルロニダーゼ阻害活性の測定〉
ヒアルロニダーゼ阻害作用に関する評価は、以下の方法で行った。
ヒアルロニダーゼ(type IV-S from Bovine testis、Sigma社製)溶液の100μl(4,500unit/ml;0.1M酢酸緩衝液(pH4.0)に溶解)に試料200μlを加えて、37℃20分間放置した。次に酵素活性化剤(Compound 48/80、Sigma社製)溶液(0.5mg/ml;0.1M酢酸緩衝液(pH4.0)に溶解)200μlを加え、37℃で20分間放置した後、基質であるヒアルロン酸カリウム(from rooster comb、和光純薬社製)溶液(0.8mg/ml;0.1M酢酸緩衝液(pH4.0)に溶解)500μlを入れ、37℃で40分間放置した。次いで0.4N 水酸化ナトリウム溶液200μlを加えて反応を停止させた後、0.8Mホウ酸溶液0.2mlを加え、沸水中で3分間加熱した。室温まで冷却後、1%p-ジメチルアミノベンズアルデヒド酢酸溶液6mlを加え、37℃で20分間放置した後、585nmにおける吸光度を測定した。試料は実施例2で得られたものを0.1M酢酸緩衝液(pH4.0)で0.2%濃度に調製した。上記と同様の酵素反応と吸光度測定を、試料溶液の代わりに緩衝液を添加して行った。さらにそれぞれの場合について酵素を添加せずに緩衝液を加えて同様の操作と測定を行った。以下の数2により阻害率を算出し、上述の測定結果を表2に示した。
<Measurement of hyaluronidase inhibitory activity>
Evaluation of the hyaluronidase inhibitory action was performed by the following method.
Add 200 μl of sample to 100 μl of hyaluronidase (type IV-S from Bovine testis, manufactured by Sigma) solution (4,500 units / ml; dissolved in 0.1 M acetate buffer (pH 4.0)) and leave at 37 ° C. for 20 minutes. did. Next, 200 μl of enzyme activator (Compound 48/80, Sigma) solution (0.5 mg / ml; dissolved in 0.1 M acetate buffer (pH 4.0)) was added, and the mixture was allowed to stand at 37 ° C. for 20 minutes. 500 μl of a substrate potassium hyaluronate (from rooster comb, manufactured by Wako Pure Chemical Industries, Ltd.) solution (0.8 mg / ml; dissolved in 0.1 M acetic acid buffer (pH 4.0)) was added and left at 37 ° C. for 40 minutes. did. Next, 200 μl of 0.4N sodium hydroxide solution was added to stop the reaction, 0.2 ml of 0.8M boric acid solution was added, and the mixture was heated in boiling water for 3 minutes. After cooling to room temperature, 6 ml of 1% p-dimethylaminobenzaldehyde acetic acid solution was added, and the mixture was allowed to stand at 37 ° C. for 20 minutes, and then the absorbance at 585 nm was measured. The sample obtained in Example 2 was adjusted to a concentration of 0.2% with 0.1 M acetate buffer (pH 4.0). The same enzyme reaction and absorbance measurement as described above were performed by adding a buffer solution instead of the sample solution. Further, in each case, the same operation and measurement were performed by adding a buffer solution without adding an enzyme. The inhibition rate was calculated by the following formula 2, and the above measurement results are shown in Table 2.
(化粧水)
10名のパネルを対象に、上記化粧水を1回/日、2ヶ月間使用したところ、内7名が乾燥肌、肌荒れが改善され、皮膚のハリや弾力を回復した。
また、本実施例のオオウメガサソウ抽出物(実施例2)の代わりに、実施例1又は実施例3のオオウメガサソウ抽出物を使用した以外は同一の方法で製造した各化粧水について、本実施例とはパネル対象者を変更し、本実施例と同一方法でパネル試験を行った結果、本実施例のパネル試験結果と同様に乾燥肌、肌荒れが改善され、皮膚のハリや弾力回復の効果を奏した。
(Lotion)
When the above lotion was used once a day for 2 months for 10 panelists, 7 of them improved dry skin and rough skin and recovered skin firmness and elasticity.
In addition, each lotion produced in the same manner as in Example 1 or Example 3 except that the perennial extract of Example 1 or Example 3 was used in place of the extract of Example 2 (Example 2). As a result of changing the panel subject and performing the panel test in the same manner as in this example, dry skin and rough skin were improved as in the panel test result of this example, and the effect of restoring skin elasticity and elasticity was improved. I played.
(ヘアリキッド)
10名のパネルを対象に、上記ヘアリキッドを1回/日、3ヶ月間使用したところ、内6名の頭皮のかゆみが改善された。
また、本実施例のオオウメガサソウ抽出物(実施例1)の代わりに、実施例2又は実施例3のオオウメガサソウ抽出物を使用した以外は同一の方法で製造した各ヘアリキッドについて、本実施例とはパネル対象者を変更し、本実施例と同一方法でパネル試験を行った結果、本実施例のパネル試験結果と同様に頭皮のかゆみ改善効果を奏した。
(Hair liquid)
When the above-mentioned hair liquid was used once per day for 3 months for 10 panels, itching of the scalp of 6 persons improved.
Moreover, about each hair liquid manufactured by the same method except using the perennial extract of Example 2 or Example 3 instead of the perennial extract of Example (Example 1), this Example As a result of changing the panel subject and performing the panel test in the same manner as in this example, the effect of improving scalp itchiness was obtained in the same manner as the panel test result in this example.
(キャンデー)
風邪をひいて喉の痛みを生じている4名のパネルを対象に、上記キャンディを飲食したとこを、内3名が喉の痛みが無くなるか、軽減された。
また、本実施例のオオウメガサソウ抽出物(実施例1)の代わりに、実施例2又は実施例3のオオウメガサソウ抽出物を使用した以外は同一の方法で製造した各キャンディーについて、本実施例とはパネル対象者を変更し、本実施例と同一方法でパネル試験を行った結果、本実施例のパネル試験結果と同様に喉の痛みが無くなるか、軽減する効果を奏した。
(candy)
Of the four panelists who suffered from a cold and caused sore throat, eating and drinking the above candy, three of them disappeared or were alleviated.
In addition, each candy produced by the same method as in Example 2 or 3 except that it was used in place of the perennial extract of Example (Example 1). Changed the panel subject, and as a result of performing the panel test by the same method as the present example, as in the panel test result of the present example, there was an effect of eliminating or reducing the sore throat.
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003371317A JP4247091B2 (en) | 2002-10-31 | 2003-10-30 | Skin anti-aging agent |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002319121 | 2002-10-31 | ||
JP2003172694 | 2003-06-17 | ||
JP2003371317A JP4247091B2 (en) | 2002-10-31 | 2003-10-30 | Skin anti-aging agent |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2005029556A true JP2005029556A (en) | 2005-02-03 |
JP4247091B2 JP4247091B2 (en) | 2009-04-02 |
Family
ID=34222097
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003371317A Expired - Lifetime JP4247091B2 (en) | 2002-10-31 | 2003-10-30 | Skin anti-aging agent |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP4247091B2 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1689099A1 (en) | 2005-02-04 | 2006-08-09 | Fujitsu Limited | Radio frequency repeater |
JP2007254345A (en) * | 2006-03-23 | 2007-10-04 | Naris Cosmetics Co Ltd | Maillard reaction inhibitor, skin care preparation containing the same and food and beverage |
JP2007261996A (en) * | 2006-03-28 | 2007-10-11 | Naris Cosmetics Co Ltd | Acrolein adduct-forming inhibitor, and skin external preparation and food and drink containing the same |
JP2008222633A (en) * | 2007-03-13 | 2008-09-25 | Ikeda Shokken Kk | Ultraviolet light-protecting agent |
WO2009007412A3 (en) * | 2007-07-09 | 2009-04-02 | Basf Beauty Care Solutions F | Age deglycation |
JP2010155820A (en) * | 2008-10-10 | 2010-07-15 | Hayashikane Sangyo Kk | Skin ameliorating agent, and vascular ameliorating agent, and pharmaceutical composition, food, feed and cosmetic comprising the same |
CN106074301A (en) * | 2016-07-31 | 2016-11-09 | 刘德金 | A kind of freckle-removing mask solution and preparation method thereof |
-
2003
- 2003-10-30 JP JP2003371317A patent/JP4247091B2/en not_active Expired - Lifetime
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1689099A1 (en) | 2005-02-04 | 2006-08-09 | Fujitsu Limited | Radio frequency repeater |
JP2007254345A (en) * | 2006-03-23 | 2007-10-04 | Naris Cosmetics Co Ltd | Maillard reaction inhibitor, skin care preparation containing the same and food and beverage |
JP2007261996A (en) * | 2006-03-28 | 2007-10-11 | Naris Cosmetics Co Ltd | Acrolein adduct-forming inhibitor, and skin external preparation and food and drink containing the same |
JP2008222633A (en) * | 2007-03-13 | 2008-09-25 | Ikeda Shokken Kk | Ultraviolet light-protecting agent |
WO2009007412A3 (en) * | 2007-07-09 | 2009-04-02 | Basf Beauty Care Solutions F | Age deglycation |
JP2010155820A (en) * | 2008-10-10 | 2010-07-15 | Hayashikane Sangyo Kk | Skin ameliorating agent, and vascular ameliorating agent, and pharmaceutical composition, food, feed and cosmetic comprising the same |
CN106074301A (en) * | 2016-07-31 | 2016-11-09 | 刘德金 | A kind of freckle-removing mask solution and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
JP4247091B2 (en) | 2009-04-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4205188B2 (en) | Maillard reaction inhibitor | |
JP3966924B2 (en) | Fibroblast growth promoter containing plant extract | |
CN111053716B (en) | Application of Fuzhuan tea extract in preparation of skin conditioning product | |
KR102113193B1 (en) | Composition for improving skin conditions comprising artemisiae annuae herba, centella asiatica and green tea extract or fraction thereof and method for improving skin conditions using the same | |
JP4388289B2 (en) | Skin aging prevention / improving agent and / or rough skin prevention / improving agent kit | |
JP2002241293A (en) | Maillard reaction inhibitor | |
JP2004346045A (en) | Cosmetic additive, bathing agent and health food containing sake lees extract obtained in brewing of sake using deep seawater | |
JP2020502172A (en) | Cosmetic composition containing Chinese herbal extract as active ingredient | |
JP4247091B2 (en) | Skin anti-aging agent | |
JP4425163B2 (en) | Anti-aging cosmetics | |
JP6055667B2 (en) | Collagen production promoter | |
KR101820531B1 (en) | Composition for preventing hair loss or promoting hair growth with Nipa fruticans wurmb | |
TW202102239A (en) | Antiaging agent, antioxidant, antiinflammatory agent and whitening agent, and cosmetic | |
JP2001316275A (en) | Collagen production promoter, estrogen-like agent, collagenase inhibitor, skin cosmetic, food and drink | |
KR100564107B1 (en) | Cosmetic composition comprising plant extract having anti-aging effect | |
KR101762314B1 (en) | Cosmetic composition containing plant extract for improving skin condition | |
JPH06329545A (en) | Hyaluronidase inhibitor containing galenical extract as active ingredient | |
KR102290291B1 (en) | Composition for improving moisturizing skin containing fermented blueberry and black rice extracts | |
JP2003342179A (en) | Agent for aging prevention | |
JP4169814B2 (en) | A topical skin preparation containing agave or sisal extract | |
KR20180082058A (en) | A cosmetic composition for skin desquamation comprising natural complex extract | |
KR20170137559A (en) | Composition for improving skin condition comprising herb extracts mixture | |
JP2003212748A (en) | Collagen production promoter, skin cosmetic and beauty food and drink | |
TWI857919B (en) | Anti-inflammatory agents and cosmetics | |
JP6022333B2 (en) | Ceramide production promoter |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20061011 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061017 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20061012 |
|
RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7421 Effective date: 20070411 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070621 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20080624 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080708 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080901 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20080930 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081125 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20081205 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090106 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090109 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4247091 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120116 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150116 Year of fee payment: 6 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |