JPH0369322B2 - - Google Patents
Info
- Publication number
- JPH0369322B2 JPH0369322B2 JP18366084A JP18366084A JPH0369322B2 JP H0369322 B2 JPH0369322 B2 JP H0369322B2 JP 18366084 A JP18366084 A JP 18366084A JP 18366084 A JP18366084 A JP 18366084A JP H0369322 B2 JPH0369322 B2 JP H0369322B2
- Authority
- JP
- Japan
- Prior art keywords
- sezamol
- acid
- tyrosinase activity
- added
- ether
- 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
Links
- 230000000694 effects Effects 0.000 claims description 28
- 102000003425 Tyrosinase Human genes 0.000 claims description 25
- 108060008724 Tyrosinase Proteins 0.000 claims description 25
- 239000003112 inhibitor Substances 0.000 claims description 16
- -1 cis-3-hexenyl Chemical group 0.000 claims description 15
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Chemical group OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- ZAKOWWREFLAJOT-ADUHFSDSSA-N [2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] acetate Chemical group CC(=O)OC1=C(C)C(C)=C2OC(CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-ADUHFSDSSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([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 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000001444 retinoyl group Chemical group O=C([*])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C1=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C1(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000946 retinyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C([H])=C(C([H])([H])[H])/C([H])=C([H])/C1=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C1(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 16
- 239000000203 mixture Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000005755 formation reaction Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 8
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 8
- 206010015150 Erythema Diseases 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 231100000321 erythema Toxicity 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 230000002087 whitening effect Effects 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- 239000002537 cosmetic Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- UATRONWBYDQKSQ-UHFFFAOYSA-N 3-methyl-1-(3-methylbut-2-enoxy)but-2-ene Chemical compound CC(C)=CCOCC=C(C)C UATRONWBYDQKSQ-UHFFFAOYSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 229940081310 piperonal Drugs 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 206010014970 Ephelides Diseases 0.000 description 3
- 208000003351 Melanosis Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 206010042496 Sunburn Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229960004441 tyrosine Drugs 0.000 description 3
- JKXQKGNGJVZKFA-UHFFFAOYSA-N 1-chloro-3-methylbut-2-ene Chemical compound CC(C)=CCCl JKXQKGNGJVZKFA-UHFFFAOYSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 241000252229 Carassius auratus Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 208000012641 Pigmentation disease Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 235000013824 polyphenols Nutrition 0.000 description 2
- 239000011607 retinol Substances 0.000 description 2
- 229960003471 retinol Drugs 0.000 description 2
- 235000020944 retinol Nutrition 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000000475 sunscreen effect Effects 0.000 description 2
- 239000000516 sunscreening agent Substances 0.000 description 2
- 235000007586 terpenes Nutrition 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- PEYUIKBAABKQKQ-AFHBHXEDSA-N (+)-sesamin Chemical compound C1=C2OCOC2=CC([C@H]2OC[C@H]3[C@@H]2CO[C@@H]3C2=CC=C3OCOC3=C2)=C1 PEYUIKBAABKQKQ-AFHBHXEDSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- JHEPBQHNVNUAFL-AATRIKPKSA-N (e)-hex-1-en-1-ol Chemical compound CCCC\C=C\O JHEPBQHNVNUAFL-AATRIKPKSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
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- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- JTAXUBKTCAOMTN-UHFFFAOYSA-N Abietinol Natural products CC(C)C1=CC2C=CC3C(C)(CO)CCCC3(C)C2CC1 JTAXUBKTCAOMTN-UHFFFAOYSA-N 0.000 description 1
- AFHJQYHRLPMKHU-XXWVOBANSA-N Aloin Natural products O=C1c2c(O)cc(CO)cc2[C@H]([C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O2)c2c1c(O)ccc2 AFHJQYHRLPMKHU-XXWVOBANSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
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- 208000001382 Experimental Melanoma Diseases 0.000 description 1
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- 108010024636 Glutathione Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
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- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- DJWYOLJPSHDSAL-UHFFFAOYSA-N Pantethine Natural products OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)C(O)C(C)(C)CO DJWYOLJPSHDSAL-UHFFFAOYSA-N 0.000 description 1
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- YTGJWQPHMWSCST-UHFFFAOYSA-N Tiopronin Chemical compound CC(S)C(=O)NCC(O)=O YTGJWQPHMWSCST-UHFFFAOYSA-N 0.000 description 1
- 108010058907 Tiopronin Proteins 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
- GQRUHVMVWNKUFW-LWYYNNOASA-N abieta-7,13-dien-18-ol Chemical compound OC[C@]1(C)CCC[C@]2(C)[C@@H](CCC(C(C)C)=C3)C3=CC[C@H]21 GQRUHVMVWNKUFW-LWYYNNOASA-N 0.000 description 1
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- OTIKYRVPXSEIPV-UHFFFAOYSA-N acetic acid;phenylhydrazine Chemical compound CC(O)=O.NNC1=CC=CC=C1 OTIKYRVPXSEIPV-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- CPUHNROBVJNNPW-UHFFFAOYSA-N aloin A Natural products OC1C(O)C(O)C(CO)OC1OC1C2=CC(CO)=CC(O)=C2C(=O)C2=C(O)C=CC=C21 CPUHNROBVJNNPW-UHFFFAOYSA-N 0.000 description 1
- AFHJQYHRLPMKHU-WEZNYRQKSA-N aloin B Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1[C@H]1C2=CC(CO)=CC(O)=C2C(=O)C2=C(O)C=CC=C21 AFHJQYHRLPMKHU-WEZNYRQKSA-N 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 229940067596 butylparaben Drugs 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000003764 chromatophore Anatomy 0.000 description 1
- 150000004777 chromones Chemical class 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005562 fading Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 235000011957 flavonols Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
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- 229960003180 glutathione Drugs 0.000 description 1
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 208000000069 hyperpigmentation Diseases 0.000 description 1
- 230000003810 hyperpigmentation Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- AFHJQYHRLPMKHU-UHFFFAOYSA-N isobarbaloin Natural products OC1C(O)C(O)C(CO)OC1C1C2=CC(CO)=CC(O)=C2C(=O)C2=C(O)C=CC=C21 AFHJQYHRLPMKHU-UHFFFAOYSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical class OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical class OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000036564 melanin content Effects 0.000 description 1
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- 238000002844 melting Methods 0.000 description 1
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- 230000006371 metabolic abnormality Effects 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
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- QFOHBWFCKVYLES-UHFFFAOYSA-N n-butyl para-hydroxybenzoate Natural products CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 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
- 235000014593 oils and fats Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- ZNXZGRMVNNHPCA-VIFPVBQESA-N pantetheine Chemical class OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS ZNXZGRMVNNHPCA-VIFPVBQESA-N 0.000 description 1
- DJWYOLJPSHDSAL-ROUUACIJSA-N pantethine Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)CO DJWYOLJPSHDSAL-ROUUACIJSA-N 0.000 description 1
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- 239000011581 pantethine Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
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- ASUAYTHWZCLXAN-UHFFFAOYSA-N prenol Chemical compound CC(C)=CCO ASUAYTHWZCLXAN-UHFFFAOYSA-N 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
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- 229930002330 retinoic acid Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
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- 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
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Cosmetics (AREA)
Description
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INDUSTRIAL APPLICATION FIELD The present invention relates to cosmetics for the purpose of, for example, controlling stains and freckles, preventing sunburn, and treating pigmentation disorders, etc.
This invention relates to tyrosinase activity inhibitors used in pharmaceuticals, etc. BACKGROUND ART Melanin is a black to brown ecological pigment that is said to be produced by oxidative polymerization of tyrosine, and its formation is promoted by the enzyme tyrosinase. The formation of melanin itself is part of the body's defense mechanism, and the well-controlled and uniform formation of melanin is
It is preferable both for maintaining the normal functions of living organisms and from the viewpoint of cosmetics. However, local excessive melanin formation caused by external stimulation such as ultraviolet rays or metabolic abnormalities causes cosmetically unfavorable phenomena such as age spots, freckles, and hyperpigmentation. Although the true cause of such local hypermelaninosis is unknown, the phenomenon is attributed to hyperactivity of the enzyme tyrosinase involved in melanin formation. By inhibiting tyrosinase activity, tyrosinase activity inhibitors suppress such excessive melanin formation and promote whitening of the skin. Utilizing this skin whitening effect, tyrosinase activity inhibitors are used in cosmetics, pharmaceuticals, etc. for the purpose of controlling age spots and freckles, preventing sunburn, and treating hyperpigmentation disorders. Conventionally, crude drug extracts (Japanese Patent Application Laid-Open No. 79033/1983) have been used as tyrosinase activity inhibitors for the purpose of whitening effects.
No. 53-88333, No. 54-2344, No. 57-163307
), mixture of ascorbic acid and crude drug extract (JP-A-52-79032), mixture of ascorbic acid and aloin (JP-A-51-95140), ascorbic acid and 2,4,6-hydroxypropiophenone (Japanese Unexamined Patent Publications No. 51-101138), silk peptide compounds (Unexamined Japanese Patent Application Nos. 57-3827 and 57-40495),
Lipoic acid compounds (JP-A-57-123107), tiopronin-based compounds (JP-A-56-154409), glutathione-based compounds (JP-A-57-134410), pantethine-based compounds (JP-A-56-73012) ), pantetheine compounds (JP-A-57-7405, JP-A No. 59-36606)
No.), trobolone compounds (Japanese Patent Application Laid-open No. 56-26842,
56-147704, 56-147705), chromone compounds (JP-A-55-11410, JP-A-55-143908),
Flavonol compounds (JP-A No. 55-92305, same)
No. 55-111411, No. 55-157580, No. 58-131911
), pyrone compounds (JP-A-53-3538, JP-A No. 57)
-72978, 57-134409), kojic acid compounds (JP-A-53-6432, JP-A-56-7776, JP-A-56-77272)
No. 59-33207), and many others have been disclosed. Problems to be solved by the invention Conventionally known tyrosinase activity inhibitors are:
Some lack efficacy, some seem to have problems with stability and safety, and some are difficult to obtain. There is still no ideal solution that satisfies these requirements. Currently, tyrosinase activity inhibitors, while having excellent efficacy as the first priority, also have stability, safety, and
There is a demand for the emergence of an ideal product that also satisfies economic efficiency. Means for Solving the Problems In order to solve the above problems, the present inventors have extensively searched for substances that inhibit the melanin formation reaction from tyrosine by tyrosinase. , 4-methylenedioxyphenol and its ester derivatives and ether derivatives have been found to be highly effective in inhibiting tyrosinase activity, and have also demonstrated their stability, safety,
After thorough consideration of economic efficiency and the application of its whitening effect to cosmetics, pharmaceuticals, etc., we have confirmed that these compounds can constitute almost ideal tyrosinase activity inhibitors, and have developed the present invention. completed. That is, the present invention is based on the general formula () [In the formula, R is a hydrogen atom, ethyl, n-butyl, n
- from the group consisting of hexyl, cis-3-hexenyl, 2-methoxyethyl, benzyl, phenylethyl, cinnamyl, geranyl, prenyl, retinyl, tocopheryl, rosinyl, acetyl, butyryl, caproyl, oleoyl, benzoyl, cinnamoyl, abiethyl and retinoyl. Indicates at least one selected item. ] A tyrosinase activity inhibitor containing at least one 3,4-methylenedioxyphenol derivative represented by the following as an active ingredient. 3,4-Methylenedioxyphenol (referred to as Cezamol.Hereinafter referred to as Cezamol) has the structural formula of formula () This compound is naturally contained in small amounts in sesame oil along with sezamin, sezamorin, etc., and the purified product is a colorless crystal (melting point: 64°C) with a weak phenolic aroma. Although it is widely known that sezamol has an antioxidant effect, no literature has yet been found that reports that sezamol has an excellent tyrosinase activity inhibitory effect. Sezamol is naturally contained in sesame oil, but since it is in a trace amount, it is not a good idea to separate and purify it, and it is better to obtain sezamol by a synthetic method. Sezamol was synthesized by adding a peracetic acid solution containing a small amount of p-toluenesulfonic acid to piperonal and reacting at room temperature according to the method of Koden et al. [Rec.trav.chim., 55 , 815-20 (1936)]. After cooling, peracetic acid is decomposed with an alkali, unreacted piperonal is removed with a mixture of phenylhydrazine acetic acid, and then solvent extraction is carried out, thereby easily achieving a good yield. A specific example is as follows. Synthesis of Sezamol 420 g of 20% peracetic acid containing a small amount of p-toluenesulfonic acid is slowly added to 150 g of piperonal while stirring while maintaining the internal temperature at 30°C. After the reaction mixture is allowed to stand overnight to complete the reaction, most of the acetic acid is distilled off under reduced pressure. After adding alcoholic potassium hydroxide to decompose peracetic acid, 10 g of phenylhydrazine and 50 g of 4N acetic acid are added to remove unreacted piperonal. After making it acidic by adding dilute sulfuric acid, it is extracted with ether. The ether layer was washed with aqueous sodium bicarbonate and then with water, dried over Glauber's salt, and the ether was distilled off to obtain about 90 g of solid sezamol. This is re-purified from toluene. Sezamol has a phenolic hydroxyl group,
The skin irritation was low, and even when a 12.5% acetone solution of sezamol was applied to shaved guinea pigs, no erythema or redness was observed, and no sensitization was observed. The carboxylic acids that participate in the formation of the ester derivatives of sezamol used as active ingredients in the present invention include aliphatic saturated and unsaturated carboxylic acids such as acetic acid, butyric acid, caproic acid, oleic acid, etc., aromatic carboxylic acids such as benzoic acid, etc. , cinnamic acid, linear and cyclic terpene carboxylic acids, such as rosin acid,
Retinoic acid, etc. Also, the alcohols that participate in the formation of ether derivatives of sezamol include aliphatic saturated and unsaturated alcohols, such as ethanol, butanol, methyl cellosolve, hexenol, prenyl alcohol, aromatic alcohols, such as benzyl alcohol, phenethyl alcohol. etc., linear and cyclic terpene alcohols such as geraniol, retinol, modinol, abietinol, etc. Ester and ether derivatives of sezamol are:
It can be synthesized by conventional methods from sezamol and carboxylic acids or alcohols. For example, sezamol acetate is produced by adding acetic anhydride containing a small amount of phosphoric acid to sezamol, reacting at room temperature, adding water to separate the organic layer, and separating the organic layer.
Obtained by distillation. Sezamol prenyl ether can also be produced by adding prenyl chloride and a small amount of benzyltriethylammonium chloride to sezamol soda salt and stirring and refluxing the mixture for several hours.
It is obtained by separating the organic layer and distilling it.
Specific examples are as follows. Synthesis of sezamol acetate 30 g of acetic anhydride and 0.2 g of phosphoric acid were added to 20 g of sezamol, stirred at room temperature for 7 hours, and then left overnight.
Add 100ml of water, stir for 2 hours, take the separated organic layer, wash thoroughly with water, distill the organic layer, collect a fraction of Bb83°~84°/0.2mmHg,
g of sezamol acetate is obtained. Synthesis of Cezamol Prenyl Ether 126 g of 5% caustic soda solution was added to 21 g of Cezamol to make soda salt, and prenyl chloride 33
g and 5 g of benzyltriethylammonium chloride were added, and the mixture was stirred and refluxed at 70 to 75°C for 7 hours. After standing overnight, the separated organic layer was taken, washed with dilute hydrochloric acid and then water, and then distilled to Bb97° ~
Collect the 100°/0.3 mmHg fraction to obtain about 18 g of sezamol prenyl ether. When sezamol contains impurities, it may darken over time, but its ester and ether derivatives show almost no deterioration over time. Furthermore, when comparing the tyrosinase activity inhibitory effects of sezamol and its ester and ether derivatives, the derivatives tend to be slightly lower; however, when using them, it is important to consider not only the inhibitory effect but also the stability and safety of the substance. It is desirable to use the material by taking into consideration its properties, mixability with the base material, absorption into the skin, etc. Cezamol and its derivatives as tyrosinase activity inhibitors can be used in cosmetics and pharmaceuticals at an addition amount of 0.01 to 5% by weight to the base material, but in most cases, an addition amount of 0.01 to 0.2% by weight is used. A sufficient effect can be obtained. The addition method is by dissolving it in a hydrophilic solvent such as ethanol, glycerin, propylene glycol, or a lipophilic solvent such as triethyl citrate, benzyl benzoate, dioctyl phthalate, etc.
When the base material already contains the above-mentioned solvents, oils and fats, surfactants, and other components that easily dissolve sezamol and its derivatives, they can be added directly. EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited to these Examples. Example 1 Tyrosinase activity inhibition effect of sezamol and its derivatives Take 2.0 ml of 0.1N phosphate buffer (PH7.0) containing 0.1% L-tyrosine and 0.002% copper sulfate, and add sezamol or its derivatives to this. each
Add 0.05 ml of ethanol solution containing 0.2%.
Next, 0.05 ml of an enzyme solution prepared by dissolving 10 mg of commercially available tyrosinase (manufactured by Sigma Chemical Co., 500 units per mg) in 10 ml of 0.1N phosphate buffer (PH.0) is added. The mixture was shaken at 37°C for 60 minutes, then held at 85°C for 5 minutes to stop the reaction, 2 ml of 0.1N phosphate buffer (PH7.0) was added, and the absorbance (OD) at a wavelength of 580 nm was measured. When the inhibition rate of the tyrosinase reaction was determined using the following formula, the results shown in Table 1 were obtained. Inhibition rate = (1 - OD when active inhibitor is added - blank OD / OD when active inhibitor is not added - blank OD) x 100
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ãã®çµæã第ïŒè¡šã«ç€ºãã[Table] Example 2 Effect of inhibiting tyrosinase activity in melanoma cells B-16 melanoma cells, which are melanin-producing tumor cells, were inoculated into Eagle MEM medium (manufactured by Nippon Suisan) containing 20% fetal bovine serum, and then cezamol, A 0.5% dimethyl sulfoxide solution containing 0.2% each of sezamol retinoate and sezamol retinol ether was added, and 1/2 of the culture medium was refreshed every 2 days at 37°C and a carbon dioxide concentration of 5%. After 6 days of culture, cells were separated. Melanin content was determined by Uitztaker's method [Dev.
Biol., 8 , 99-127 (1963)], wavelength 400 nm.
It was expressed as the optical density (OD) per 10 6 cells. Tyrosinase activity was determined by suspending the separated cells in a 0.001N caustic soda solution containing 0.5% sodium cholate and homogenizing the cells according to the method of Iwata et al. [Proc. Japan Acad., 56 , 562-567 (1980)]. After disrupting the cells, ultra-high-speed centrifugation (30,000 rpm, 20 minutes) was performed, and the resulting supernatant was ÎE/min per 106 cells at a wavelength of 475 nm.
It was expressed as The results are shown in Table 2.
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It is known that it is absorbed into cells and acts effectively as a tyrosinase activity inhibitor within the cells. Example 3 Fading experiment on black goldfish Water was placed in tanks A, B, C, and D with a diameter of 30 cm and a depth of 20 cm.
10, and add 0.5% each of cezamol, cezamol acetate, and cezamol prenyl ether.
10 ml of ethanol solution was added, D was used as a control (no additives), and 3 black-eyed gilders were placed in each tank and reared. The water in the aquarium was refreshed every 3 days. All the goldfish in the aquariums to which the inhibitor had been added began to discolor from around the third week. Table 3 shows the degree of discoloration after 6 weeks and the number of chromatophores in the scales as determined by microscopic observation.
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ãã[Table] The results shown in Table 3 were sufficient to infer the skin whitening effect of sezamol and its derivatives. Example 4 cream agent (weight %) Monoglyceride 3.5 stearic acid 4.7 cethyl alcoholic 1.7 light flow flowing paraphrodes 14.0 isopropyl mirifin 3.0 stear lil alcohol 3.0 stearlil alcohol 3.2 butyl paraben 0.05 methyl paraben 0.05 triet Noamin 05 Trietnol Amin 0. 1 Pure Water 60.4 50 % Cesemall ethanol solution 1.0 Fragrance 0.3 100.0 First, mix the above formulation excluding glycerin, water, and fragrance, heat to about 70°C, stir thoroughly, keep at that temperature, add glycerin and water, and stir and mix further. do. Thereafter, the mixture was cooled with gentle stirring, and when the temperature dropped to about 50°C, a fragrance was added, and the mixture was further cooled to room temperature while stirring to obtain a cream. A cream sample prepared in the same manner as above was used as a blank, except that pure water was used instead of the 50% sezamol ethanol solution in the above formulation. In addition, from the above formulation, excluding the 50% Cezamol ethanol solution, 5% of Filtrasol-A (manufactured by Norda, USA), a commercially available sunscreen, was added instead, and 60.4% of pure water was added. A cream prototyped in the same manner as above was used as a positive control, except that the amount was set to 56.4% (hereinafter referred to as the control product). A sunburn test was conducted using these and a cream containing sezamol with the above formulation. Five Hartley guinea pigs weighing 350 to 400 g were used, and their shoulder blades were shaved and shaved. Divide the 3cm x 3cm hair removal area into 4 parts, and place 1
4 cm x 1 cm square test plots were prepared, two of which were filled with blanks, the remaining one was filled with cream containing sezamol (hereinafter referred to as the test product), and the remaining one was filled with a control product. It was applied at a concentration of 0.02 mg/cm 2 . The unapplied area of the material was shielded from light. And with 5 lamps of National FL20SE, 10cm
The beam was irradiated for 10 minutes at a distance of 10 minutes (total energy amount was 1.8 Joules). As a criterion for evaluation, the following scores were given for erythema that appeared on the skin 24 hours and 48 hours after irradiation. Note that no evaluation was made regarding edema because only a few edema appeared overall. Rating: No erythema at all 0 Slight erythema 1 Obvious erythema 2 Moderate erythema 3 The results of the test based on this evaluation are shown in Table 4.
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ããã®ã§ããã[Table] From the results in Table 4, it can be seen that Sezamol has a much superior effect (same effect with about 1/10th the amount) compared to commercially available sunscreens. Example 5 Ointment (wt%) Carite butter 40.0 Olive oil 20.0 Beeswax 20.0 Paraffin 19.9 Sezamol n-butyl ether 0.1 100.0 Each component was mixed according to the above recipe, heated to about 70°C and stirred well to make it sufficiently uniform. I poured it into a container and left it to cool to make an ointment. Example 6 Lotion (wt%) Ethanol 20.0 Propylene glycol 5.0 Glycerin 4.5 Methylparaben 0.1 Pure water 70.0 Sezamol acetate 0.1 Fragrance 0.3 100.0 A lotion was prepared by mixing each component according to the above recipe. Effects of the Invention The tyrosinase activity inhibitor of the present invention, which contains sezamol or its ester derivative or ether derivative as an active ingredient, substantially satisfies all of the requirements such as excellent efficacy, stability, safety, and economical efficiency, and has sufficient whitening effect. It has a sun protection effect and a pigmentation treatment effect.
Claims (1)
âããã·ã«ãã·ã¹âïŒâããã»ãã«ãïŒâã¡ãã
ã·ãšãã«ããã³ãžã«ãããšãã«ãšãã«ãã·ã³ãã
ã«ãã²ã©ãã«ããã¬ãã«ãã¬ããã«ããã³ããšãª
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ã«ããã³ãŸã€ã«ãã·ã³ãã¢ã€ã«ãåã³ã¬ããã€ã«
ããæã矀ããéžã°ãããã®å°ãªããšãïŒçš®ã瀺
ããã ã§è¡šããããïŒïŒïŒâã¡ãã¬ã³ãžãªãã·ããšããŒ
ã«èªå°äœã®å°ãªããšãïŒçš®ãæå¹æåãšããŠå«æ
ããããã·ããŒãŒæŽ»æ§é»å®³å€ã ïŒ ïŒïŒïŒâã¡ãã¬ã³ãžãªãã·ããšããŒã«èªå°äœ
ã®å«æéã0.01ãïŒééïŒ ã§ããç¹èš±è«æ±ã®ç¯å²
第ïŒé ã«èšèŒã®ããã·ããŒãŒæŽ»æ§é»å®³å€ã[Claims] 1 General formula () [In the formula, R is a hydrogen atom, ethyl, n-butyl, n
- selected from the group consisting of hexyl, cis-3-hexenyl, 2-methoxyethyl, benzyl, phenylethyl, cinnamyl, geranyl, prenyl, retinyl, tocopheryl, acetyl, butyryl, caproyl, oleoyl, benzoyl, cinnamoyl, and retinoyl. Indicates at least one type of thing. ] A tyrosinase activity inhibitor containing at least one 3,4-methylenedioxyphenol derivative represented by the following as an active ingredient. 2. The tyrosinase activity inhibitor according to claim 1, wherein the content of the 3,4-methylenedioxyphenol derivative is 0.01 to 5% by weight.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP18366084A JPS6163609A (en) | 1984-09-04 | 1984-09-04 | Inhibitor of tyrosinase activity |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP18366084A JPS6163609A (en) | 1984-09-04 | 1984-09-04 | Inhibitor of tyrosinase activity |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6163609A JPS6163609A (en) | 1986-04-01 |
JPH0369322B2 true JPH0369322B2 (en) | 1991-10-31 |
Family
ID=16139694
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP18366084A Granted JPS6163609A (en) | 1984-09-04 | 1984-09-04 | Inhibitor of tyrosinase activity |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6163609A (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04500824A (en) * | 1989-07-25 | 1992-02-13 | ã€ãŒã¹ããã³ ã³ãã㯠ã«ã³ãã㌠| Skin treatment methods to reverse the effects of photoaging |
GR1000937B (en) * | 1990-08-24 | 1993-03-16 | Eastman Kodak Co | Skin treatment and method for the restoration of the skin against sun effects |
-
1984
- 1984-09-04 JP JP18366084A patent/JPS6163609A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS6163609A (en) | 1986-04-01 |
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