JP4944372B2 - Acrolein adduct formation inhibitor, and skin external preparation and health supplement containing the same - Google Patents
Acrolein adduct formation inhibitor, and skin external preparation and health supplement containing the same Download PDFInfo
- Publication number
- JP4944372B2 JP4944372B2 JP2004351375A JP2004351375A JP4944372B2 JP 4944372 B2 JP4944372 B2 JP 4944372B2 JP 2004351375 A JP2004351375 A JP 2004351375A JP 2004351375 A JP2004351375 A JP 2004351375A JP 4944372 B2 JP4944372 B2 JP 4944372B2
- Authority
- JP
- Japan
- Prior art keywords
- acrolein
- leaves
- labiatae
- rosaceae
- leaf
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 title claims description 77
- 230000015572 biosynthetic process Effects 0.000 title claims description 17
- 239000003112 inhibitor Substances 0.000 title claims description 12
- 238000002360 preparation method Methods 0.000 title description 15
- 235000015872 dietary supplement Nutrition 0.000 title description 8
- 235000004789 Rosa xanthina Nutrition 0.000 claims description 32
- 241000207923 Lamiaceae Species 0.000 claims description 29
- 241000220222 Rosaceae Species 0.000 claims description 29
- 244000124853 Perilla frutescens Species 0.000 claims description 19
- 244000269722 Thea sinensis Species 0.000 claims description 18
- 239000000284 extract Substances 0.000 claims description 16
- 235000004347 Perilla Nutrition 0.000 claims description 12
- 241000220317 Rosa Species 0.000 claims description 12
- 235000006468 Thea sinensis Nutrition 0.000 claims description 12
- 230000003712 anti-aging effect Effects 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 241000219071 Malvaceae Species 0.000 claims description 11
- 244000062730 Melissa officinalis Species 0.000 claims description 11
- 241000196324 Embryophyta Species 0.000 claims description 10
- VEYYWZRYIYDQJM-ZETCQYMHSA-N N(2)-acetyl-L-lysine Chemical compound CC(=O)N[C@H](C([O-])=O)CCCC[NH3+] VEYYWZRYIYDQJM-ZETCQYMHSA-N 0.000 claims description 10
- 240000002657 Thymus vulgaris Species 0.000 claims description 7
- 235000007303 Thymus vulgaris Nutrition 0.000 claims description 7
- 244000144730 Amygdalus persica Species 0.000 claims description 6
- 235000003261 Artemisia vulgaris Nutrition 0.000 claims description 6
- 240000006891 Artemisia vulgaris Species 0.000 claims description 6
- 241000208838 Asteraceae Species 0.000 claims description 6
- 241000208150 Geraniaceae Species 0.000 claims description 6
- 241000218377 Magnoliaceae Species 0.000 claims description 6
- 235000010654 Melissa officinalis Nutrition 0.000 claims description 6
- 235000006040 Prunus persica var persica Nutrition 0.000 claims description 6
- 241001122767 Theaceae Species 0.000 claims description 6
- 235000009569 green tea Nutrition 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 235000020333 oolong tea Nutrition 0.000 claims description 6
- 235000013616 tea Nutrition 0.000 claims description 6
- 235000020334 white tea Nutrition 0.000 claims description 6
- 235000003840 Amygdalus nana Nutrition 0.000 claims description 5
- 241000208152 Geranium Species 0.000 claims description 5
- 241000220299 Prunus Species 0.000 claims description 5
- 235000011432 Prunus Nutrition 0.000 claims description 5
- 240000007591 Tilia tomentosa Species 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 5
- 235000014774 prunus Nutrition 0.000 claims description 5
- 235000021018 plums Nutrition 0.000 claims description 4
- 238000012360 testing method Methods 0.000 claims description 4
- 235000011446 Amygdalus persica Nutrition 0.000 claims description 3
- 241000546188 Hypericum Species 0.000 claims description 3
- 235000017309 Hypericum perforatum Nutrition 0.000 claims description 3
- 235000009508 confectionery Nutrition 0.000 claims description 3
- 239000008363 phosphate buffer Substances 0.000 claims description 3
- 241000209035 Ilex Species 0.000 claims description 2
- 235000003325 Ilex Nutrition 0.000 claims description 2
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 claims description 2
- 235000021016 apples Nutrition 0.000 claims description 2
- 235000014486 Hydrangea macrophylla Nutrition 0.000 claims 1
- 241001091442 Hydrangeaceae Species 0.000 claims 1
- 244000141359 Malus pumila Species 0.000 claims 1
- 201000005702 Pertussis Diseases 0.000 claims 1
- 238000012216 screening Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 241000218378 Magnolia Species 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 235000005206 Hibiscus Nutrition 0.000 description 9
- 235000007185 Hibiscus lunariifolius Nutrition 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 241000220225 Malus Species 0.000 description 8
- 241000218033 Hibiscus Species 0.000 description 7
- 235000004348 Perilla frutescens Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 235000011430 Malus pumila Nutrition 0.000 description 6
- 235000015103 Malus silvestris Nutrition 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 230000032683 aging Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 241000209034 Aquifoliaceae Species 0.000 description 5
- 244000052585 Rosa centifolia Species 0.000 description 5
- 235000016588 Rosa centifolia Nutrition 0.000 description 5
- 244000154511 Rosa hybrid cultivar Species 0.000 description 5
- 235000002315 Rosa hybrid cultivar Nutrition 0.000 description 5
- 239000003963 antioxidant agent Substances 0.000 description 5
- 230000003078 antioxidant effect Effects 0.000 description 5
- 235000006708 antioxidants Nutrition 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000000469 ethanolic extract Substances 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 230000002335 preservative effect Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 241000546193 Clusiaceae Species 0.000 description 4
- 241000782597 Hypericum erectum Species 0.000 description 4
- 244000188472 Ilex paraguariensis Species 0.000 description 4
- 235000003368 Ilex paraguariensis Nutrition 0.000 description 4
- 235000011158 Prunus mume Nutrition 0.000 description 4
- 244000018795 Prunus mume Species 0.000 description 4
- 235000002168 Tilia europaea Nutrition 0.000 description 4
- 240000006909 Tilia x europaea Species 0.000 description 4
- -1 acrolein amino acid Chemical class 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
- 239000002304 perfume Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 244000275701 Geranium nepalense Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102100037209 Peroxisomal N(1)-acetyl-spermine/spermidine oxidase Human genes 0.000 description 3
- 240000005809 Prunus persica Species 0.000 description 3
- 241000109329 Rosa xanthina Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 229920000768 polyamine Polymers 0.000 description 3
- 108010089000 polyamine oxidase Proteins 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 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
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000002322 Egg Proteins Human genes 0.000 description 2
- 108010000912 Egg Proteins Proteins 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 244000284380 Hibiscus rosa sinensis Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241001183967 Isodon Species 0.000 description 2
- 241001365031 Isodon japonicus Species 0.000 description 2
- 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 2
- 244000070406 Malus silvestris Species 0.000 description 2
- 206010051246 Photodermatosis Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 210000003278 egg shell Anatomy 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000003859 lipid peroxidation Effects 0.000 description 2
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000008845 photoaging Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229940032094 squalane Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 229940099259 vaseline Drugs 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- RZOVDOYFYGXAEU-NRFANRHFSA-N (2s)-6-amino-2-(hexadecylamino)hexanoic acid Chemical compound CCCCCCCCCCCCCCCCN[C@H](C(O)=O)CCCCN RZOVDOYFYGXAEU-NRFANRHFSA-N 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 1
- KNUPSOXBESCJLY-UHFFFAOYSA-N 2-methoxy-1-phenylhexan-1-one Chemical compound CCCCC(OC)C(=O)C1=CC=CC=C1 KNUPSOXBESCJLY-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- DTERQYGMUDWYAZ-ZETCQYMHSA-N N(6)-acetyl-L-lysine Chemical compound CC(=O)NCCCC[C@H]([NH3+])C([O-])=O DTERQYGMUDWYAZ-ZETCQYMHSA-N 0.000 description 1
- 241000745988 Phyllostachys Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 238000000944 Soxhlet extraction Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 241000907897 Tilia Species 0.000 description 1
- 240000007313 Tilia cordata Species 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000003323 beak Anatomy 0.000 description 1
- 230000008049 biological aging Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000008278 cosmetic cream Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 238000002481 ethanol extraction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- CMFNMSMUKZHDEY-UHFFFAOYSA-N peroxynitrous acid Chemical compound OON=O CMFNMSMUKZHDEY-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000001585 thymus vulgaris Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
Images
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Cosmetics (AREA)
Description
本発明は、アクロレインのアミノ酸やタンパク質との付加体形成阻害剤であり、その付加体形成阻害剤を含有する皮膚抗老化外用剤や抗老化健康補助食品に関する。 The present invention relates to an acrolein amino acid or protein adduct formation inhibitor, and relates to a skin anti-aging external preparation or anti-aging health supplement containing the adduct formation inhibitor.
従来より、老化を抑制する抗老化剤としては、種々のものが開発されている。このよう
な生体の老化は、２つの生物学的要因により起こることが知られている
Conventionally, various anti-aging agents that suppress aging have been developed. It is known that such biological aging is caused by two biological factors.
１つは生理的老化で、他の１つは紫外線等の暴露部に生じる光老化皮膚と呼ばれるもの
である。生理的老化は、生体内で生成した活性酸素が影響し、血管や皮膚の主な構成因子であるコラーゲン線維の変性や生理機能に係わりの深い酵素の変質による活性の低下などに関わる。光老化に感しては、紫外線の暴露が原因であるため皮膚に限られる。
One is physiological aging and the other is called photo-aging skin that occurs in exposed areas such as ultraviolet rays. Physiological aging is influenced by active oxygen generated in the living body, and is related to degeneration of collagen fibers, which are the main components of blood vessels and skin, and a decrease in activity due to alteration of enzymes deeply related to physiological functions. Sensation of photoaging is limited to the skin because it is caused by UV exposure.
生理的老化において、活性酸素種を除去することが主に検討され、スーパーオキサイドアニオン、ヒドロキシラジカル、一重項酸素、パーオキシナイトライト等に対する除去剤が提示されている。近年、活性酸素以外の老化因子としてアクロレインの関与が注目されている。 In physiological aging, removal of reactive oxygen species has been mainly studied, and removal agents for superoxide anion, hydroxy radical, singlet oxygen, peroxynitrite and the like have been proposed. In recent years, the involvement of acrolein as an aging factor other than active oxygen has attracted attention.
アクロレインはα,β-不飽和アルデヒドで反応性が高く、タンパク質（酵素やコラーゲン）の変性や細胞毒性に関わり、その細胞毒性は類縁のアルデヒドであるアセトアルデヒド、ホルムアルデヒド、アクロレインを比較するとアクロレインが最も強く、ホルムアルデヒドそしてアセトアルデヒドである。アクロレインの細胞毒性は、活性酸素の要因となりうる過酸化水素に比べても強いことが報告されている（Kenneth Ramos、etal、Toxicology and Applied Pharmacology、Vol.95、61-71 (1988)）。 Acrolein is an α, β-unsaturated aldehyde that is highly reactive and is involved in the denaturation and cytotoxicity of proteins (enzymes and collagen). Formaldehyde and acetaldehyde. It has been reported that the cytotoxicity of acrolein is stronger than hydrogen peroxide, which can be a cause of active oxygen (Kenneth Ramos, etal, Toxicology and Applied Pharmacology, Vol. 95, 61-71 (1988)).
アクロレインは、生体内ではポリアミンから生成したり（Gunnar Houen、etal、Acta Chemia Scandinavica、Vol.48、52-60 (1994)）、脂質の過酸化反応の過程で生成する（内田浩二、日本油化学会誌、Vol.47、No.11、29-37（1998））ことがわかっている。また、アクロレインはプラスティックの燃焼、たばこ煙、排気ガスや油脂の加熱によって生成される環境汚染物質の一つである。このように、アクロレインの発生過程は、活性酸素の発生過程とよくオーバーラップしており、今まで老化の原因が活性酸素というのが一般的となっているが、実はアクロレインが関与しているのではないのかとも考えられる。 Acrolein can be produced in vivo from polyamines (Gunnar Houen, etal, Acta Chemia Scandinavica, Vol. 48, 52-60 (1994)) or in the process of lipid peroxidation (Koji Uchida, Nippon Oil Chemicals). (Journal, Vol. 47, No. 11, 29-37 (1998)). Acrolein is one of the environmental pollutants generated by burning plastic, cigarette smoke, exhaust gas and oil. In this way, the generation process of acrolein overlaps well with the process of generation of active oxygen, and until now the cause of aging has generally been active oxygen, but actually acrolein is involved. It may be possible.
また、アクロレインから生体を守る検討では、ポリアミンにポリアミンオキシダーゼが作用しアクロレインを生成することから、ポリアミンオキシダーゼを阻害する特許(特開２００２−２８１９９９)とリポキシゲナーゼによる酸化過程でアクロレインが生成することからリポキシゲナーゼを阻害する特許(特開２００２-１３８０１３)が提示されている。
本発明の課題は、上記の如くアクロレインの生成を完全に抑えることが極めて困難な為、生成したアクロレインを直接補足する作用を持つ成分を提供し、それを含有する皮膚抗老化外用剤や抗老化健康補助食品を提供することである。 The object of the present invention is to provide a component having an action of directly supplementing the generated acrolein because it is extremely difficult to completely suppress the generation of acrolein as described above, and to provide a skin anti-aging external preparation or anti-aging containing the same. It is to provide health supplements.
本発明者らは、このような課題を解決するために鋭意研究を重ねた結果、生体内のポリ
アミンにポリアミンオキシダーゼが作用すること及び生体内の脂質の過酸化反応により生
成するアクロレインを直接補足する作用を持つ成分を提供することにより、アクロレイン
の体内での反応を阻害する方法が極めて有効であることを見出した。即ち、生体内のタン
パク質との付加体形成を阻害する成分を提供するという方法、及びその成分を見出し本発
明を完成するに至った。
As a result of intensive studies to solve such problems, the present inventors directly supplement acrolein produced by the action of polyamine oxidase on polyamines in vivo and lipid peroxidation in vivo. It has been found that a method for inhibiting the reaction of acrolein in the body by providing a component having an action is extremely effective. That is, the present inventors have found a method for providing a component that inhibits adduct formation with a protein in a living body and the component, and completed the present invention.
本発明のアクロレイン付加体形成抑制剤として、西洋バラ（Rosa centifolia Linne(Rosaceae)）花弁、現代バラ（RosaHybrida(Rosaceae)）花弁、ハイビスカス(Hibiscus subdariffa(Malvaceae))花、
モクレン（Magnolia
lililora(Magnoliaceae)）葉、リンゴ（Malus
pumila Mill(Rosaceae)）
葉、モモ（Prunus
persica(Rosaceae)葉、ゲンノショウコ（GeraniumnepalenseSweet(Geraniaceae)）葉、メリッサ（Melissa officinalis（Labiatae））葉、リンデン（Tilia europaea(Tiliaceae)葉、ヨモギ（Artemisia vulgaris L.(Compositae)）葉、ハチク（Phyllostachys nigra Munro(Graminae)）葉、タイム（Thymus vulgaris L.（Labiatae））葉、シソ（Perilla
frutescens Britt.（Labiatae））葉、シソ（Perilla frutescensBritt.（Labiatae））種子、梅（Prunus Mume Sieb.( (Rosaceae))種子、オトギリソウ（Hypericum erectum Thunb.（Guttiferae））全草、ヒキオコシ（Isodon
japonicus Hara（Labiatae））全草、緑茶（Thea sinensis L.(Theaceae)）、ウーロン茶、白茶、マテ（Ilex Paraguariensis(Aquifoliaceae)茶抽出物の1種又は2種以上を含有した皮膚外用剤および健康補助食品は、安全性が高く、広く抗老化用の皮膚外用剤及び健康補助食品として期待できる。具体的には、本発明のアクロレイン付加体形成阻害剤を配合した皮膚外用剤は、シワ・タルミ等の発生を抑制することが期待でき、又、本発明のアクロレイン付加体形成阻害剤を配合した健康補助食品は、生体中の動脈硬化を抑制することが期待できる
。
As an acrolein adduct formation inhibitor of the present invention, Western rose (Rosa centifolia Linne (Rosaceae)) petals, modern rose (RosaHybrida (Rosaceae)) petals, hibiscus (Hibiscus subdariffa (Malvaceae)) flowers,
Magnolia (Magnolia)
lililora (Magnoliaceae)) leaf, apple (Malus)
pumila Mill (Rosaceae))
Leaf, peach (Prunus)
persica (Rosaceae) leaf, GeraniumnepalenseSweet (Geraniaceae) leaf, Melissa (Melissa officinalis (Labiatae) leaf), Linden (Tilia europaea (Tiliaceae) leaf, Artemisia vulgaris L. (Compositae)) leaf, wasch ys (Ph Munro (Graminae) leaves, Thymus vulgaris L. (Labiatae) leaves, Perilla
frutescens Britt. (Labiatae) leaves, perilla (Perilla frutescensBritt. (Labiatae)) seeds, plum (Prunus Mume Sieb. ((Rosaceae)) seeds, hypericum erectum Thunb.
japonicus Hara (Labiatae) whole plant, green tea (Thea sinensis L. (Theaceae)), oolong tea, white tea, mate (Ilex Paraguariensis (Aquifoliaceae) tea extract containing one or more kinds and health aids Foods are highly safe and can be widely expected to be used as anti-aging skin external preparations and health supplements. The health supplement containing the acrolein adduct formation inhibitor of the present invention can be expected to suppress arteriosclerosis in the living body.
本発明におけるアクロレインを直接捕捉する方法は、内田らのアセチルリジンとアクロレインの付加生成物をHPLCで測定する方法（J.Biol.Chem.、Vol.273、No.26、Issue of June26、16058-16066(1998)）を改変して行った。 The method of directly capturing acrolein in the present invention is a method of measuring an addition product of acetyllysine and acrolein by Uchida et al. (J. Biol. Chem., Vol. 273, No. 26, Issue of June 26, 16058- 16066 (1998)).
即ち、0.1Mリン酸緩衝液（pH7.4）に100mMのN-アセチルリジンを溶解し、同様に0.1Mリン酸緩衝液（pH7.4）に10mMのアクロレインを溶解し、それぞれ450μLずつ取り、37℃で24時間反応させる。そこに被検試料を100μL加えて、反応液をHPLCで分析し、アクロレインとN-アセチルリジンの付加生成物を分析し、その生成量から抑制率を算出する。 That is, 100 mM N-acetyllysine was dissolved in 0.1 M phosphate buffer (pH 7.4), 10 mM acrolein was dissolved in 0.1 M phosphate buffer (pH 7.4), and 450 μL each was taken. Incubate at 37 ° C for 24 hours. 100 μL of a test sample is added thereto, the reaction solution is analyzed by HPLC, the addition product of acrolein and N-acetyllysine is analyzed, and the inhibition rate is calculated from the amount of the product.
本発明における被検試料は、アクロレインがタンパク質との付加体を生成する過程を抑制するアクロレイン付加体生成抑制剤であり、西洋バラ（Rosa centifolia Linne(Rosaceae)）花弁、現代バラ（Rosa Hybrida(Rosaceae)）花弁、ハイビスカス(Hibiscus subdariffa(Malvaceae))花、モクレン（Magnolia lililora(Magnoliaceae)）葉、リンゴ（Malus pumila Mill(Rosaceae)）葉、モモ（Prunus persica(Rosaceae)葉、ゲンノショウコ（Geranium nepalense Sweet(Geraniaceae)）葉、メリッサ（Melissa officinalis（Labiatae））葉、リンデン（Tilia europaea(Tiliaceae)葉、ヨモギ（Artemisia vulgaris L.(Compositae)）葉、ハチク（Phyllostachys nigra Munro(Graminae)）葉、タイム（Thymus vulgaris L.（Labiatae））葉、シソ（Perilla frutescens Britt.（Labiatae））葉、シソ（Perilla
frutescens Britt.（Labiatae））種子、梅（Prunus Mume Sieb.( (Rosaceae))種子、オトギリソウ（Hypericum erectum Thunb.（Guttiferae））全草、ヒキオコシ（Isodon japonicus Hara（Labiatae））全草、緑茶（Thea
sinensis L.(Theaceae)）、ウーロン茶、白茶、マテ（Ilex
Paraguariensis(Aquifoliaceae)茶の抽出物の少なくとも一種を含有させたことを特徴とする。
The test sample in the present invention is an acrolein adduct formation inhibitor that suppresses the process of acrolein producing an adduct with a protein, such as a rose (Rosa centifolia Linne (Rosaceae)) petal, a modern rose (Rosa Hybrida (Rosaceae). )) Petals, Hibiscus (Hibiscus subdariffa (Malvaceae)) flowers, magnolia (Magnolia lililora (Magnoliaceae)) leaves, apples (Malus pumila Mill (Rosaceae)) leaves, peaches (Prunus persica (Rosaceae) leaves, Geranium nepalense Sweet ( Geraniaceae) leaves, Melissa (Melissa officinalis (Labiatae)) leaves, Linden (Tilia europaea (Tiliaceae) leaves, Artemisia vulgaris L. (Compositae)) leaves, Japanese beak (Pyllostachys nigra Munro (Graminae)) leaves, Thymus vulgaris L. (Labiatae) leaves, perilla frutescens Britt. (Labiatae) leaves, perilla
frutescens Britt. (Labiatae) seeds, plums (Prunus Mume Sieb. ((Rosaceae)) seeds, hypericum erectum Thunb. (Guttiferae) whole plant, Hikikoshi (Isodon japonicus Hara (Labiatae)) whole plant, green tea (Thea
sinensis L. (Theaceae)), oolong tea, white tea, mate (Ilex
It is characterized by containing at least one kind of Paraguariensis (Aquifoliaceae) tea extract.
また、本発明は、このような西洋バラ（Rosa centifolia Linne(Rosaceae)）花弁、現代バラ（Rosa Hybrida(Rosaceae)）花弁、ハイビスカス(Hibiscus subdariffa(Malvaceae))花、モクレン（Magnolia lililora(Magnoliaceae)）葉、リンゴ（Malus pumila Mill(Rosaceae)）葉、モモ（Prunus persica(Rosaceae)葉、ゲンノショウコ（Geranium nepalense Sweet(Geraniaceae)）葉、メリッサ（Melissa officinalis（Labiatae））葉、リンデン（Tilia
europaea(Tiliaceae)葉、ヨモギ（Artemisia
vulgaris L.(Compositae)）葉、ハチク（Phyllostachys
nigra Munro(Graminae)）葉、タイム（Thymus
vulgaris L.（Labiatae））葉、シソ（Perilla frutescens Britt.（Labiatae））葉、シソ（Perilla frutescens Britt.（Labiatae））種子、梅（Prunus
Mume Sieb.( (Rosaceae))種子、オトギリソウ（Hypericum
erectum Thunb.（Guttiferae））全草、ヒキオコシ（Isodon japonicus Hara（Labiatae））全草、緑茶（Thea sinensis L.(Theaceae)）、ウーロン茶、白茶、マテ（Ilex Paraguariensis(Aquifoliaceae)茶の抽出物の少なくとも一種または二種以上を含有させた皮膚抗老化外用剤および抗老化健康補助食品である。
In addition, the present invention also provides such Western rose (Rosa centifolia Linne (Rosaceae) petals, modern rose (Rosa Hybrida (Rosaceae)) petals, hibiscus (Hibiscus subdariffa (Malvaceae)) flowers, magnolia (Magnolia lila (Magnoliaceae)). Leaves, apple (Malus pumila Mill (Rosaceae)) leaves, peach (Prunus persica (Rosaceae) leaves, geranium nepalense sweet (Geraniaceae)) leaves, Melissa (Melissa officinalis (Labiatae)) leaves, linden (Tilia)
europaea (Tiliaceae) leaves, Artemisia
vulgaris L. (Compositae)) leaf, bee (Phyllostachys)
nigra Munro (Graminae)) leaves, thyme (Thymus
vulgaris L. (Labiatae) leaves, perilla (Perilla frutescens Britt. (Labiatae)) leaves, perilla (Perilla frutescens Britt. (Labiatae)) seeds, plum (Prunus)
Mume Sieb. ((Rosaceae)) Seeds, Hypericum (Hypericum)
erectum Thunb. (Guttiferae) whole plant, Hikikoshi (Isodon japonicus Hara (Labiatae) whole plant, green tea (Thea sinensis L. (Theaceae)), oolong tea, white tea, mate (Ilex Paraguariensis (Aquifoliaceae) tea extract) A skin anti-aging topical preparation and an anti-aging health supplement containing one or more kinds.
即ち、本発明に係る抽出物は、抽出溶媒としては、各種極性有機溶媒及びそれらの混液を用いることができる。抽出物の生成は、様々な方法が用いられるが、活性炭、スチレン−ジビニルベンゼン系合成吸着剤（ＨＰ−２０：三菱化成社製）やオクタデシルシラン処理シリカ（Ｃｈｒｏｍａｔｏｒｅｘ ＯＤＳ：富士シリシア化学製）により吸着させ、適当な溶媒で溶出する方法が簡便でかつ実用的である。 That is, the extract according to the present invention can use various polar organic solvents and a mixture thereof as the extraction solvent. Various methods can be used to produce the extract, but it is adsorbed by activated carbon, styrene-divinylbenzene synthetic adsorbent (HP-20: manufactured by Mitsubishi Kasei) or octadecylsilane-treated silica (Chromatorex ODS: manufactured by Fuji Silysia Chemical). The method of eluting with an appropriate solvent is simple and practical.
また、本発明に係る抽出物の各種皮膚外用剤に対する配合量は、皮膚外用剤の実施態様、皮膚外用剤の使用形態等に応じて変動させることができるので特に限定されない。原則的には、有効量存在すれば良いことになるが、一般的には組成物中、乾燥重量に換算して０．０００１〜１００質量％が利用でき、好ましくは０．０１〜１０質量％、更に好ましくは０．５〜５．０質量％である。特に、用時調製のパウダー状の製剤等は、この本願発明に係る抽出物が１００質量％を含めた高配合率で利用されることが想定できる。 Moreover, since the compounding quantity with respect to the various skin external preparation of the extract which concerns on this invention can be fluctuate | varied according to the embodiment of a skin external preparation, the usage form of a skin external preparation, etc., it is not specifically limited. In principle, an effective amount may be present, but generally 0.0001 to 100% by mass in terms of dry weight can be used in the composition, preferably 0.01 to 10% by mass. More preferably, it is 0.5 to 5.0% by mass. In particular, it can be assumed that the powdery preparation prepared at the time of use is used at a high blending rate including 100% by mass of the extract according to the present invention.
本発明に係る皮膚外用剤の適用範囲は、特に限定されない。つまり、この発明の有効成分が有する作用効果に応じて各作用効果を利用できる全ての皮膚外用剤に適用できる。 The application range of the external preparation for skin according to the present invention is not particularly limited. That is, the present invention can be applied to all external preparations for skin that can use each function and effect according to the function and effect of the active ingredient of the present invention.
例えば、本発明に係る有効成分を各種皮膚外用剤基剤等に配合して、クリーム、乳液、化粧水、パック剤、洗顔料等に対して適用できる。また、前記各種皮膚外用剤の実施態様は、ローション、エマルジョン、軟膏、ゾル、ゲル、パウダー、スプレー、固形等の各種態様で適用できる。 For example, the active ingredient according to the present invention can be blended in various skin external preparation bases and applied to creams, emulsions, lotions, packs, face wash, and the like. Moreover, the various skin external preparations can be applied in various forms such as lotion, emulsion, ointment, sol, gel, powder, spray, and solid.
また、本発明に係る抗老化健康補助食品は、ドリンク剤、ジェル状、粉末製剤、錠剤等の剤型にすることが可能である。 Moreover, the anti-aging health supplement according to the present invention can be made into dosage forms such as drinks, gels, powder formulations, tablets and the like.
以下、実施例により本発明を詳細に説明するが、本発明はこれらに限定されるものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to these.
本実施例は、本発明のアクロレインのタンパク質との付加体形成阻害剤について、具体的な抽出例を示したものである。 This example shows a specific extraction example of the adduct formation inhibitor with the acrolein protein of the present invention.
被検体としては、西洋バラ（Rosa
centifolia Linne (Rosaceae)）花弁、現代バラ（Rosa
Hybrida(Rosaceae)）花弁、ハイビスカス(Hibiscus
subdariffa(Malvaceae))花、モクレン（Magnolia
lililora(Magnoliaceae)）葉、リンゴ（Malus
pumila Mill(Rosaceae)）葉、モモ（Prunus
persica(Rosaceae)葉、ゲンノショウコ（Geranium
nepalense Sweet(Geraniaceae)）葉、メリッサ（Melissa officinalis（Labiatae））葉、リンデン（Tilia europaea(Tiliaceae)葉、ヨモギ（Artemisia vulgaris L.(Compositae)）葉、ハチク（Phyllostachys nigra Munro(Graminae)）葉、タイム（Thymus vulgaris L.（Labiatae））葉、シソ（Perilla
frutescens Britt.（Labiatae））葉、シソ（Perilla frutescens Britt.（Labiatae））種子、梅（Prunus Mume Sieb.( (Rosaceae))種子、オトギリソウ（Hypericum erectum Thunb.（Guttiferae））全草、ヒキオコシ（Isodon
japonicus Hara（Labiatae））全草、緑茶（Thea sinensis L.(Theaceae)）、ウーロン茶、白茶、マテ（Ilex Paraguariensis(Aquifoliaceae)茶を用いた。
The subject was a Western rose (Rosa
centifolia Linne (Rosaceae) petals, modern roses (Rosa
Hybrida (Rosaceae) petals, Hibiscus
subdariffa (Malvaceae)) flower, magnolia (Magnolia)
lililora (Magnoliaceae)) leaf, apple (Malus)
pumila Mill (Rosaceae)) leaf, peach (Prunus)
persica (Rosaceae) leaves, Geranium (Geranium)
nepalense Sweet (Geraniaceae) leaf, Melissa (Melissa officinalis (Labiatae)) leaf, Linden (Tilia europaea (Tiliaceae) leaf, Artemisia vulgaris L. (Compositae)) leaf, Bee (Pyllostachys nigra Munro (Graminae)) leaf, Thymus (Thymus vulgaris L. (Labiatae)) leaf, perilla (Perilla)
frutescens Britt. (Labiatae) leaves, perilla (Perilla frutescens Britt. (Labiatae)) seeds, plums (Prunus Mume Sieb. ((Rosaceae)) seeds, hypericum erectum Thunb. (Guttiferae) whole plants, Hikokoshi (Isodon)
japonicus Hara (Labiatae) whole plant, green tea (Thea sinensis L. (Theaceae)), oolong tea, white tea, mate (Ilex Paraguariensis (Aquifoliaceae) tea) were used.
上記、抽出物の抽出法は、水であれば、60℃で数時間抽出し得ることができる。エタノール抽出であれば、ソックスレー抽出を行うことによって得ることができる。 The extraction method for the extract can be extracted at 60 ° C. for several hours if it is water. If it is ethanol extraction, it can be obtained by performing Soxhlet extraction.
以下、抽出に関して具体例を示す。
〔実験例１〕現代バラ花水抽出物の作成
原材料として、現代バラ花部の乾燥物を１００ｇ使用した。前記原材料１００ｇに精製水１５００ｍLを加え、60℃で3時間抽出した後、Ｎｏ．１３１濾紙にて濾過し、ろ液を１１００ｍL得た。
Hereinafter, a specific example is shown regarding extraction.
[Experimental Example 1] 100 g of a dried product of a modern rose flower part was used as a raw material for producing a modern rose flower water extract. After adding 1500 mL of purified water to 100 g of the raw material and extracting at 60 ° C. for 3 hours, It filtered with 131 filter paper, and 1100 mL of filtrate was obtained.
〔実験例２〕モクレン葉エタノール抽出物の作成
原材料として、モクレン葉の乾燥物を１００ｇ使用した。前記原材料１００ｇに９９．５％エタノール１０００ｍＬを加え、室温で3日間抽出した後Ｎｏ．１３１濾紙にて濾過し、ろ液を８５０ｍL得た。
[Experimental Example 2] 100 g of dried magnolia leaf was used as a raw material for preparing magnolia leaf ethanol extract. To 100 g of the raw material, 1000 mL of 99.5% ethanol was added and extracted at room temperature for 3 days. It filtered with 131 filter paper and obtained 850 mL of filtrate.
本実施例は、本発明のアクロレインのタンパク質との付加体形成阻害剤について、抑制
率を試験したものである。
〔実験例３〕アクロレインとN-アセチルリジンの付加体形成阻害率の測定
（１）実験方法
50mM N-アセチルリジン450μL(50mMPBS(pH7.4))、10mMアクロレイン450μL(50mMPBS(pH7.4))、試料100μLを混合し、37℃で24時間放置後、HPLCで分析を行った。陽性対照として、類似の反応と思われる糖とアミノ酸やタンパク質と起こるメイラード反応の阻害剤としてとして知られるアミノグアニジンを用いて比較を行った。試料濃度は1％の溶液を用いて行った。
In this example, the inhibition rate of the acrolein protein adduct formation inhibitor of the present invention was tested.
[Experimental Example 3] Measurement of adduct formation inhibition rate of acrolein and N-acetyllysine (1) Experimental method
450 μL of 50 mM N-acetyllysine (50 mM PBS (pH 7.4)), 450 μL of 10 mM acrolein (50 mM PBS (pH 7.4)), and 100 μL of the sample were mixed, left at 37 ° C. for 24 hours, and then analyzed by HPLC. As a positive control, a comparison was made using aminoguanidine, which is known as an inhibitor of the Maillard reaction that occurs with sugars and amino acids and proteins that appear to be similar reactions. The sample concentration was 1%.
（２）HPLC条件
カラム：DAISOPAK-SP120
ODS-BP(150mm×6mm)
温度：室温
移動相：5%MeOH in 0.1%TFA
検出：UV227nm
注入量：5μL
流量：1.5mL/min
(2) HPLC condition column: DAISOPAK-SP120
ODS-BP (150mm × 6mm)
Temperature: Room temperature Mobile phase: 5% MeOH in 0.1% TFA
Detection: UV227nm
Injection volume: 5μL
Flow rate: 1.5mL / min
水抽出物のアクロレイン付加体形成阻害作用を表1に示す。（濃度１％，＊印は０．１％） Table 1 shows the acrolein adduct formation inhibitory action of the water extract. (Concentration 1%, * mark 0.1%)
エタノール抽出物のアクロレイン付加体形成阻害作用を表2に示す。（濃度１％，＊印は０．１％） Table 2 shows the acrolein adduct formation inhibitory action of the ethanol extract. (Concentration 1%, * mark 0.1%)
表１、２の結果より、西洋バラ（Rosa
centifolia Linne(Rosaceae)）花弁、現代バラ（Rosa
Hybrida(Rosaceae)）花弁、ハイビスカス(Hibiscus
subdariffa(Malvaceae))花、モクレン（Magnolia
lililora(Magnoliaceae)）葉、リンゴ（Malus
pumila Mill(Rosaceae)）葉、モモ（Prunus
persica(Rosaceae)葉、ゲンノショウコ（Geranium
nepalense Sweet(Geraniaceae)）葉、メリッサ（Melissa officinalis（Labiatae））葉、リンデン（Tilia europaea(Tiliaceae)葉、ヨモギ（Artemisia vulgaris L.(Compositae)）葉、ハチク（Phyllostachys nigra Munro(Graminae)）葉、タイム（Thymus vulgaris L.（Labiatae））葉、シソ（Perilla
frutescens Britt.（Labiatae））葉、シソ（Perilla frutescens Britt.（Labiatae））種子、梅（Prunus Mume Sieb.( (Rosaceae))種子、オトギリソウ（Hypericum erectum Thunb.（Guttiferae））全草、ヒキオコシ（Isodon
japonicus Hara（Labiatae））全草、緑茶（Thea sinensis L.(Theaceae)）、ウーロン茶、白茶、マテ（Ilex Paraguariensis(Aquifoliaceae)茶にアクロレインとN-アセチルリジンとの付加体の形成を阻害する作用が強いことを確認した。
From the results shown in Tables 1 and 2, Western roses (Rosa
centifolia Linne (Rosaceae) petals, modern roses (Rosa
Hybrida (Rosaceae) petals, Hibiscus
subdariffa (Malvaceae)) flower, magnolia (Magnolia)
lililora (Magnoliaceae)) leaf, apple (Malus)
pumila Mill (Rosaceae)) leaf, peach (Prunus)
persica (Rosaceae) leaves, Geranium (Geranium)
nepalense Sweet (Geraniaceae) leaf, Melissa (Melissa officinalis (Labiatae)) leaf, Linden (Tilia europaea (Tiliaceae) leaf, Artemisia vulgaris L. (Compositae)) leaf, Bee (Pyllostachys nigra Munro (Graminae)) leaf, Thymus (Thymus vulgaris L. (Labiatae)) leaf, perilla (Perilla)
frutescens Britt. (Labiatae) leaves, perilla (Perilla frutescens Britt. (Labiatae)) seeds, plums (Prunus Mume Sieb. ((Rosaceae)) seeds, hypericum erectum Thunb. (Guttiferae) whole plants, Hikokoshi (Isodon)
japonicus Hara (Labiatae) whole plant, green tea (Thea sinensis L. (Theaceae)), oolong tea, white tea, mate (Ilex Paraguariensis (Aquifoliaceae) tea) has the effect of inhibiting the formation of adducts of acrolein and N-acetyllysine Confirmed strong.
＜処方例１＞化粧水
（成分名） （質量％）
現代バラ花水抽出物 １０．０
グリセリン ５．０
ポリオキシエチレンソルビタンモノラウレート（２０Ｅ．０） １．５
エタノール ８．０
クエン酸トリエチル ２．０
防腐剤・酸化防止剤 適量
精製水 残部
<Formulation example 1> lotion (component name) (mass%)
Modern rose flower water extract 10.0
Glycerin 5.0
Polyoxyethylene sorbitan monolaurate (20E.0) 1.5
Ethanol 8.0
Triethyl citrate 2.0
Preservative / Antioxidant
Purified water balance
＜処方例２＞化粧用クリーム
（成分名） （質量％）
梅種子エタノール抽出物 ５．０
ミツロウ ２．０
ステアリルアルコール ５．０
ステアリン酸 ８．０
スクワラン １０．０
自己乳化型グリセリルモノステアレート ３．０
ポリオキシエチレンセチルエーテル（２０Ｅ．０） １．０
グリセリン ５．０
水酸化カリウム ０．３
香料 適量
防腐剤・酸化防止剤 適量
精製水 残部
<Formulation example 2> Cosmetic cream (component name) (mass%)
Plum seed ethanol extract 5.0
Beeswax 2.0
Stearyl alcohol 5.0
Stearic acid 8.0
Squalane 10.0
Self-emulsifying glyceryl monostearate 3.0
Polyoxyethylene cetyl ether (20E.0) 1.0
Glycerin 5.0
Potassium hydroxide 0.3
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of purified water
＜処方例３＞乳液
（成分名） （質量％）
モクレン葉水抽出物 ０．０１
スクワラン ８．００
ワセリン ２．００
ミツロウ ０．５０
ソルビタンセスキオレエート ０．８０
ポリオキシエチレンオレイルエーテル（２０Ｅ．０） １．２０
カルボキシビニルポリマー ０．２０
グリセリン １．５０
水酸化カリウム ０．１０
エタノール ７．００
香料 適量
防腐剤・酸化防止剤 適量
精製水 残部
<Prescription Example 3> Emulsion (component name) (mass%)
Magnolia leaf water extract 0.01
Squalane 8.00
Vaseline 2.00
Beeswax 0.50
Sorbitan sesquioleate 0.80
Polyoxyethylene oleyl ether (20E.0) 1.20
Carboxyvinyl polymer 0.20
Glycerin 1.50
Potassium hydroxide 0.10
Ethanol 7.00
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of purified water
＜処方例４＞パック剤
（成分名） （質量％）
西洋バラ花水抽出物 ０．５
酢酸ビニル樹脂エマルジョン １５．０
ポリビニルアルコール １０．０
ホホバ油 ３．０
グリセリン ５．０
酸化チタン ８．０
カオリン ７．０
エタノール ５．０
香料 適量
防腐剤・酸化防止剤 適量
精製水 残部
<Prescription Example 4> Packing agent (component name) (mass%)
Western rose flower water extract 0.5
Vinyl acetate resin emulsion 15.0
Polyvinyl alcohol 10.0
Jojoba oil 3.0
Glycerin 5.0
Titanium oxide 8.0
Kaolin 7.0
Ethanol 5.0
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of purified water
＜処方例５＞軟膏
（成分名） （質量％）
ハイビスカス花エタノール抽出物 ０．００１
酢酸トコフェロール ０．５００
パラジメチルアミノ安息香酸オクチル ４．０００
ブチルメトキシベンゾイルメタン ４．０００
ステアリルアルコール １８．０００
モクロウ ２０．０００
グリセリンモノステアリン酸エステル ０．３００
ワセリン ３３．０００
香料 適量
防腐剤・酸化防止剤 適量
精製水 残部
<Prescription Example 5> Ointment (component name) (mass%)
Hibiscus flower ethanol extract 0.001
Tocopherol acetate 0.500
Octyl paradimethylaminobenzoate 4.00
Butylmethoxybenzoylmethane 4.00
Stearyl alcohol 18.000
Owl 20.000
Glycerin monostearate 0.300
Vaseline 33.000
Perfume Appropriate amount of preservative / antioxidant Appropriate amount of purified water
＜処方例６＞ドリンク剤
ヒキオコシ水抽出物 ２．０
クエン酸 ０．１
ビタミンC 適量
精製水 残部
<Prescription Example 6> Drink agent toad water extract 2.0
Citric acid 0.1
Vitamin C appropriate amount purified water balance
＜処方例７＞粉末製剤
ハチク葉水抽出物 ３０．０
卵殻カルシウム １０．０
乳糖 １５．０
セルロース
残部
<Prescription Example 7> Powder preparation Hachiku leaf water extract 30.0
Eggshell calcium 10.0
Lactose 15.0
cellulose
The rest
＜処方例８＞錠剤
ブドウ葉エタノール抽出物 １０．０
卵殻カルシウム １０．０
乳糖 ２０．０
澱粉 ７．０
デキストリン ８．０
硬化油 ５．０
セルロース
残部
<Prescription Example 8> Tablet Grape Leaf Ethanol Extract 10.0
Eggshell calcium 10.0
Lactose 20.0
Starch 7.0
Dextrin 8.0
Hardened oil 5.0
cellulose
The rest
本発明は、植物抽出物を含有した安全性の高いアクロレイン付加体形成抑制剤であり、皮
膚抗老化外用剤および抗老化健康補助食品等広く応用が期待できる
。
The present invention is a highly safe acrolein adduct formation inhibitor containing a plant extract, and can be widely applied to skin anti-aging external preparations and anti-aging health supplements.
Claims (1)
２）次に反応液を高速液体クロマトグラフィーで分析し、アクロレインとN−アセチルリジンの付加生成物を分析するステップ。
３）２）で得られたアクロレインとN−アセチルリジンの付加生成物の生成量から抑制率を算出するステップ。
１）〜３）で得られた被検試料の抑制率を陽性対象物としてアミノグアニジンを用いた結果と比較し、アクロレインとＮ−アセチルリジンとの付加体の生成の阻害を評価することからなる抗老化製品に使用し得るアクロレイン付加体形成阻害剤の選別方法により選別したバラ科植物の西洋バラ（Ｒｏｓａ ｃｅｎｔｉｆｏｌｉａ Ｌｉｎｎｅ(Ｒｏｓａｃｅａｅ)）花弁、現代バラ（Ｒｏｓａ Ｈｙｂｒｉｄａ (Ｒｏｓａｃｅａｅ)）花弁、梅（Ｐｒｕｎｕｓ ＭｕｍｅＳｉｅｂ(Ｒｏｓａｃｅａｅ)種子、リンゴ（Ｍａｌｕｓｐｕｍｉｌａ Ｍｉｌｌ(Ｒｏｓａｃｅａｅ)）葉、モモ（Ｐｒｕｎｕｓ ｐｅｒｓｉｃａ(Ｒｏｓａｃｅａｅ)葉、シソ科植物のメリッサ（Ｍｅｌｉｓｓａ ｏｆｆｉｃｉｎａｌｉｓ（Ｌａｂｉａｔａｅ））葉、ヒキオコシ（Ｉｓｏｄｏｎ ｊａｐｏｎｉｃｕｓ Ｈａｒａ（Ｌａｂｉａｔａｅ））全草、シソ（Ｐｅｒｉｌｌａ ｆｒｕｔｅｓｃｅｎｓ Ｂｒｉｔｔ （Ｌａｂｉａｔａｅ））葉、シソ（Ｐｅｒｉｌｌａ ｆｒｕｔｅｓｃｅｎｓ Ｂｒｉｔｔ（Ｌａｂｉａｔａｅ））種子、タイム（Ｔｈｙｍｕｓ ｖｕｌｇａｒｉｓＬ.（Ｌａｂｉａｔａｅ））葉、ツバキ科ツバキ属のチャノキを使用する緑茶（Ｔｈｅａｓｉｎｅｎｓｉｓ L.(Ｔｈｅａｃｅａｅ)）、ウーロン茶、白茶、オトギリソウ科のオトギリソウ（Ｈｙｐｅｒｉｃｕｍｅｒｅｃｔｕｍ Tｈｕｎｂ.（Ｇｕｔｔｉｆｅｒａｅ））全草、アオイ科のハイビスカス(Ｈｉｂｉｓｃｕｓ ｓｕｂｄａｒｉｆｆａ(Ｍａｌｖａｃｅａｅ))花、モクレン科のモクレン（Ｍａｇｎｏｌｉａ ｌｉｌｉｌｏｒａ(Ｍａｇｎｏｌｉａｃｅａｅ)）葉、フウロソウ科のゲンノショウコ（Ｇｅｒａｎｉｕｍｎｅｐａｌｅｎｓｅ Ｓｗｅｅｔ(Ｇｅｒａｎｉａｃｅａｅ)）葉、シナノキ科のリンデン（Ｔｉｌｉａ ｅｕｒｏｐａｅａ(Ｔｉｌｉａｃｅａｅ)葉、キク科のヨモギ（Ａｒｔｅｍｉｓｉａ ｖｕｌｇａｒｉｓ Ｌ.(Ｃｏｍｐｏｓｉｔａｅ)）葉、イネ科のハチク（Ｐｈｙｌｌｏｓｔａｃｈｙｓ ｎｉｇｒａ Ｍｕｎｒｏ(Ｇｒａｍｉｎａｅ)）葉、モチノキ科のマテ（Ｉｌｅｘ Ｐａｒａｇｕａｒｉｅｎｓｉｓ (Ａｑｕｉｆｏｌｉａｃｅａｅ)茶の抽出物の少なくとも一種を含有することを特徴とするアクロレイン付加体形成阻害剤。
1) A step of dissolving N-acetyllysine, acrolein and a test sample in a phosphate buffer and reacting them at 37 ° C. for 24 hours.
2) Next, the reaction solution is analyzed by high performance liquid chromatography, and the addition product of acrolein and N-acetyllysine is analyzed.
3) A step of calculating the inhibition rate from the amount of addition product of acrolein and N-acetyllysine obtained in 2).
Comparing the inhibition rate of the test samples obtained in 1) to 3) with the results using aminoguanidine as a positive target, and evaluating the inhibition of the formation of adducts of acrolein and N-acetyllysine Rosacetifolia Linne (Rosaceae) petals, Rose (Hybrida (Rosaaceae)) petals, plums (Prunus MumeSieb) selected by a screening method for acrolein adduct formation inhibitors that can be used in anti-aging products (Rosaceae) seeds, apples (Maluspumilla Mill (Rosaceae)) leaves, peaches (Prunus persica (Rosaceae) leaves, Melissa officinalis (Labiatae)) leaves, hydrangeas (Isosokosi) japonicus Hara (Labiatae)) whole plant, Perilla frescens Britt (Labiatae) leaves, Perilla frescens Britt (Labiatae) seeds, Thymus vulgaris L. Green tea (Theasinensis L. (Theaceae)), oolong tea, white tea, Hypericum pertussis (Hypericerectum Thunb. (Gutiferaae)) (Magnoliaceae)) Leaf, Fuuro Geranium leaf (Geriumnepalense Sweet (Geraniaceae)), Linden (Tiliaauropaea (Tiliaceae)), Artemisia vulgaris L. (Compositae) )) Leaves, acrolein adduct formation inhibitor characterized by containing at least one extract of Ilex Paraguariansis (Aquifoliaacea) tea.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004351375A JP4944372B2 (en) | 2004-12-03 | 2004-12-03 | Acrolein adduct formation inhibitor, and skin external preparation and health supplement containing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004351375A JP4944372B2 (en) | 2004-12-03 | 2004-12-03 | Acrolein adduct formation inhibitor, and skin external preparation and health supplement containing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006160630A JP2006160630A (en) | 2006-06-22 |
| JP4944372B2 true JP4944372B2 (en) | 2012-05-30 |
Family
ID=36663052
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004351375A Expired - Lifetime JP4944372B2 (en) | 2004-12-03 | 2004-12-03 | Acrolein adduct formation inhibitor, and skin external preparation and health supplement containing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4944372B2 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5039314B2 (en) * | 2006-03-28 | 2012-10-03 | 株式会社ナリス化粧品 | Acrolein adduct formation inhibitor, and external preparation for skin and food and drink containing the same |
| JP5063947B2 (en) * | 2006-07-18 | 2012-10-31 | 株式会社ナリス化粧品 | Acrolein adduct formation inhibitor, and skin anti-aging external preparation and anti-aging food and drink containing the same |
| EP2455134B1 (en) | 2007-04-19 | 2016-05-11 | Mary Kay, Inc. | Magnolia extract containing compositions |
| JP5159241B2 (en) * | 2007-10-18 | 2013-03-06 | 株式会社 資生堂 | Ligament cell activator |
| JP5164681B2 (en) * | 2008-06-12 | 2013-03-21 | 株式会社ナリス化粧品 | Lip cosmetics and candy and chewing gum |
| JP2011195524A (en) * | 2010-03-23 | 2011-10-06 | Kose Corp | Elastase activity inhibitor |
| KR101474998B1 (en) * | 2012-11-28 | 2014-12-19 | 롯데푸드 주식회사 | Composition comprising extracts of white tea for the care of skin wrinkle |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07324025A (en) * | 1994-05-31 | 1995-12-12 | Sankoudou:Kk | External agent for suppressing maillard reaction |
| JP2002138013A (en) * | 2000-10-27 | 2002-05-14 | Pias Arise Kk | Hne-and-acrolein formation inhibiting and hne-and- acrolein decomposition promoting agent, and skin aging care preparation for external use |
| JP2002281999A (en) * | 2001-03-29 | 2002-10-02 | Kazue Igarashi | Compound for therapy of uremia, method for selecting the same and therapeutic agent of uremia containing the compound |
-
2004
- 2004-12-03 JP JP2004351375A patent/JP4944372B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP2006160630A (en) | 2006-06-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5441232B2 (en) | Maillard reaction inhibitor | |
| CN102665709A (en) | Skin clarifying complex, use of said complex, cosmestic or pharmaceutical composition comprising said complex and method for application thereof | |
| JP3502415B2 (en) | Maillard reaction inhibitor | |
| WO2021175450A1 (en) | COMPOSITION OR OAT EXTRACT COMPRISING AVENANTHRAMIDE AND ß-GLUCAN | |
| JP4195840B2 (en) | Maillard reaction inhibitor | |
| US20100240603A1 (en) | Expression inhibitor of nuclear transcription factor ap-1 and pharmaceuticals and products using the same | |
| JP4944372B2 (en) | Acrolein adduct formation inhibitor, and skin external preparation and health supplement containing the same | |
| JP5634844B2 (en) | Bitter taste inhibitor | |
| JP5063947B2 (en) | Acrolein adduct formation inhibitor, and skin anti-aging external preparation and anti-aging food and drink containing the same | |
| JPH08259431A (en) | Maillard reaction inhibitor and external preparation for skin containing the same | |
| JP2006273811A (en) | Maillard reaction inhibitor | |
| JP5717317B2 (en) | Pharmaceutical use of compounds | |
| JP2002179592A (en) | Composition for removing abnormal proteins | |
| KR101512064B1 (en) | Method for manufacturing functional cosmetic composite using no allergic bee venom | |
| KR101904501B1 (en) | Cosmetic compositions for improving skin wrinkles or skin elasticity comprising fucosterol | |
| KR101797526B1 (en) | Hair cosmetic composition containing an extract of Dendropanax morbifera ferment | |
| JP4866012B2 (en) | Acrolein adduct formation inhibitor, skin external preparation and health supplement containing the same | |
| JP5039314B2 (en) | Acrolein adduct formation inhibitor, and external preparation for skin and food and drink containing the same | |
| KR102557210B1 (en) | Composition for Anti-glycation Property Comprising Decurcinol as Active Ingredient | |
| JP2008024601A (en) | Inhibitor for acrolein adduct formation, skin anti-aging external preparation and anti-aging food and beverage containing the same | |
| JP6047793B2 (en) | Enzyme activity inhibitor | |
| JP6985130B2 (en) | Composition for Inhibiting Phosphodiesterase | |
| JP2017141204A (en) | GRANDIFLORIC ACID DERIVATIVE EXHIBITING NF-κB INHIBITORY EFFECT AND MANUFACTURING METHOD THEREFOR | |
| KR101989067B1 (en) | Composition Containing Coumestrin | |
| KR20140140338A (en) | Acai berry extracts for improving blood circulation and Hypertension and process for preparation thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20071130 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20100402 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20101012 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101213 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111101 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111228 |
|
| 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: 20120207 |
|
| 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: 20120302 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4944372 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: 20150309 Year of fee payment: 3 |
|
| 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 |
|
| 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 |
|
| 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 |