JPH04235110A - Tyrosinase-inhibitor - Google Patents
Tyrosinase-inhibitorInfo
- Publication number
- JPH04235110A JPH04235110A JP3002021A JP202191A JPH04235110A JP H04235110 A JPH04235110 A JP H04235110A JP 3002021 A JP3002021 A JP 3002021A JP 202191 A JP202191 A JP 202191A JP H04235110 A JPH04235110 A JP H04235110A
- Authority
- JP
- Japan
- Prior art keywords
- tyrosinase
- compound
- agent
- inhibitor
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 101710147108 Tyrosinase inhibitor Proteins 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 102000003425 Tyrosinase Human genes 0.000 abstract description 15
- 108060008724 Tyrosinase Proteins 0.000 abstract description 15
- 239000003795 chemical substances by application Substances 0.000 abstract description 12
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 abstract description 10
- 239000002537 cosmetic Substances 0.000 abstract description 9
- 230000002401 inhibitory effect Effects 0.000 abstract description 9
- 239000000243 solution Substances 0.000 abstract description 9
- 235000013305 food Nutrition 0.000 abstract description 7
- 229960000271 arbutin Drugs 0.000 abstract description 5
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 abstract description 5
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 abstract description 4
- 229960004705 kojic acid Drugs 0.000 abstract description 4
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 abstract description 4
- 229920002138 Eckol Polymers 0.000 abstract description 3
- ARZMNZGBFNSOIR-UHFFFAOYSA-N Eckol Natural products OC1=CC(O)=C2OC3=CC(C)=CC(O)=C3OC2=C1OC1=CC(O)=CC(O)=C1 ARZMNZGBFNSOIR-UHFFFAOYSA-N 0.000 abstract description 3
- 239000007864 aqueous solution Substances 0.000 abstract description 3
- PCZZRBGISTUIOA-UHFFFAOYSA-N eckol Chemical compound OC1=CC(O)=CC(OC=2C=3OC4=C(O)C=C(O)C=C4OC=3C(O)=CC=2O)=C1 PCZZRBGISTUIOA-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 235000019126 equol Nutrition 0.000 description 9
- ADFCQWZHKCXPAJ-UHFFFAOYSA-N indofine Natural products C1=CC(O)=CC=C1C1CC2=CC=C(O)C=C2OC1 ADFCQWZHKCXPAJ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- ADFCQWZHKCXPAJ-GFCCVEGCSA-N equol Chemical compound C1=CC(O)=CC=C1[C@@H]1CC2=CC=C(O)C=C2OC1 ADFCQWZHKCXPAJ-GFCCVEGCSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 230000002087 whitening effect Effects 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 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 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000003205 fragrance Substances 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000006071 cream Substances 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 235000014102 seafood Nutrition 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 235000012055 fruits and vegetables Nutrition 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- -1 polyoxyethylene Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 241000220225 Malus Species 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 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 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 206010014970 Ephelides Diseases 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 208000003351 Melanosis Diseases 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229920001131 Pulp (paper) Polymers 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000007854 depigmenting agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- CAYPFLMKYYVWAT-UHFFFAOYSA-N dodecanoic acid;ethanol Chemical compound CCO.CCCCCCCCCCCC(O)=O CAYPFLMKYYVWAT-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000008099 melanin synthesis Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 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
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 239000013535 sea water Substances 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Storage Of Fruits Or Vegetables (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】0001
【発明の分野】本発明は、皮膚美白剤、食品等の黒変・
褐変防止剤等として使用可能なチロシナーゼ阻害剤に関
する。[Field of the Invention] The present invention relates to skin whitening agents, blackening agents, etc.
The present invention relates to a tyrosinase inhibitor that can be used as an anti-browning agent, etc.
【０００２】0002
【発明の解決しようとする問題点】人間の皮膚に発生す
るシミ、ソバカス等は主として日焼け等によって起る組
織中のメラニンの形成に原因を有する。また魚介類、青
果物等の生鮮食料品の黒変もメラニンの形成を原因とす
るものである。Problems to be Solved by the Invention The stains, freckles, etc. that occur on human skin are mainly caused by the formation of melanin in tissues caused by sunburn, etc. The formation of melanin is also responsible for the darkening of fresh foods such as seafood and fruits and vegetables.
【０００３】メラニンは、最初にチロシンがチロシナー
ゼにより酵素的に酸化され、その後数段階の反応を経て
形成されることが知られている。[0003] Melanin is known to be formed by first enzymatically oxidizing tyrosine by tyrosinase, and then through several reaction steps.
【０００４】従って、チロシナーゼの活性を有効に阻害
する物質は、皮膚美白化粧料、食品の黒変防止剤等に使
用するのに極めて有用である。[0004] Therefore, substances that effectively inhibit tyrosinase activity are extremely useful for use in skin whitening cosmetics, anti-blackening agents for foods, and the like.
【０００５】[0005]
【問題を解決するための手段】本発明者等は、上記背景
に鑑み、チロシナーゼ活性阻害物質を探求したところ、
下記一般式Ｉ：[Means for solving the problem] In view of the above background, the present inventors have searched for tyrosinase activity inhibitors and found that
General formula I below:
【０００６】[0006]
【化４】[C4]
【０００７】［式中、Ｒは水素原子またはヒドロキシル
基を表す］を有する化合物が顕著なチロシナーゼ阻害活
性を有することを見出し、本発明を完成するに至った。It was discovered that a compound having the formula [wherein R represents a hydrogen atom or a hydroxyl group] has remarkable tyrosinase inhibitory activity, and the present invention was completed.
【０００８】従って本発明は、下記一般式ＩTherefore, the present invention provides the following general formula I
【０００９
】0009
]
【化５】[C5]
【００１０】［式中、Ｒは水素原子またはヒドロキシル
基を表す］を有する化合物を活性成分とするチロシナー
ゼ阻害剤である。[0010] This is a tyrosinase inhibitor containing a compound having the formula [wherein R represents a hydrogen atom or a hydroxyl group] as an active ingredient.
【００１１】上記一般式を有する化合物は、下記のエク
コール（ｅｃｋｏｌ）及びヒドロキシエクコール（ｈｙ
ｄｒｏｘｙｅｃｋｏｌ）である。Compounds having the above general formula include eckol and hydroxyequol (hy) shown below.
droxyyeckol).
【００１２】0012
【化６】[C6]
【００１３】上記した化合物はいずれも公知の化合物で
あるが、チロシナーゼ阻害活性を有することは知られて
いなかったものである。[0013] All of the above-mentioned compounds are known compounds, but they were not known to have tyrosinase inhibitory activity.
【００１４】[0014]
【実施例】上記一般式Ｉの化合物、即ち、エクコール及
びヒドロキシエクコールを使用して各化合物のチロシナ
ーゼ阻害活性を測定した。エクコールは、Ｙ．Ｆｕｋｕ
ｓｈｉｍａ等，Ｃｈｅｍｉｓｔｒｙ Ｌｅｔｔｅｒｓ，
１９８５， ７３５． に記載の方法により、ヒドロ
キシエクコールは、Ｋ．Ｗ．Ｇｌｏｍｂｉｔｚａ，Ｇ．
Ｇｅｒｓｂｅｒｇｅｒ， Ｐｈｙｔｏｃｈｅｍｉｓｔ
ｒｙ，２４， ５４３ （１９８５）に記載の方法によ
りそれぞれ製造した。EXAMPLE The tyrosinase inhibitory activity of each compound was measured using the compounds of the above general formula I, ie, equol and hydroxyequol. Excor is Y. Fuku
shima et al., Chemistry Letters,
1985, 735. Hydroxyequol can be prepared by the method described in K. W. Glombitza, G.
Gersberger, Phytochemist
ry, 24, 543 (1985).
【００１５】得られた各化合物のＮＭＲスペクトルを以
下に示す。但し、ヒドロキシエクコールは、アセチル化
してヘキサアセチルヒドロキシエクコールとして測定し
た。
エクコール
１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６ ） ５．７５ （２
Ｈ，ｔ）， ５．８２（１Ｈ，ｄ）， ５．８３（１Ｈ
，ｔ）， ５．９８（１Ｈ，ｄ），６．１６（１Ｈ，ｓ
）， ９．１７（２Ｈ，ｓ）， ９．１９（１Ｈ，ｓ）
， ９．２０（１Ｈ，ｓ）， ９．４８（１Ｈ，ｓ），
９．５３（１Ｈ，ｓ）， １３Ｃ−ＮＭＲ（ＤＭＳＯ
−ｄ６ ） １６０．４（ｓ）， １５８．７（ｓｘ２
）， １５３．０（ｓ）， １４６．１（ｓ）， １４
５．９（ｓ）， １４２．７（ｓ）， １３７．３（
ｓ）， １２３．５（ｓ）， １２２．６（ｓ）， ９
８．７（ｄ）， ９８．４（ｄ）， ９６．４（ｄ），
９４．０（ｄｘ３） ヘキサアセチルヒドロキシエク
コール
１Ｈ−ＮＭＲ（ＣＤＣｌ３ ） １．７３（３Ｈ，ｓ
）， １．９９（３Ｈ，ｓ）， ２．０９（３Ｈ，ｓ）
， ２．２１（６Ｈ，ｓ）， ２．３１（３Ｈ，ｓ），
６．５３（２Ｈ，ｄ）， ６．６３（１Ｈ，ｓ），
６．６７（１Ｈ，ｔ）， ６．６７（１Ｈ，ｓ）， １
３Ｃ−ＮＭＲ（ＣＤＣｌ３ ） １６８．６（ｓ），
１６８．５５（ｓ）， １６８．２（ｓ）， １６８．
０（ｓ）， １６６．６（ｓ）， １５７．９（ｓ），
１５１．６（ｓ），１４４．３（ｓ）， １４１．３
（ｓ）， １３９．３（ｓ）， １３７．６（ｓ），
１３６．４（ｓ）， １３４．８（ｓ）， １３２．９
（ｓ）， １３１．９（ｓ）， １３１．４（ｓ），
１１４．６（ｓ）， １１２．８（ｄ） １１０．２（
ｄ） １０８．７（ｄ） １０６．４（ｄ）， ２１
．１（ｑ）， ２０．７（ｑ）， ２０．５（ｑ），
２０．４（ｑ）， １９．４（ｑ）チロシナーゼ阻害試
験
各化合物の０．０５％水溶液を試料とし、下記の試験手
順により行った。The NMR spectra of each compound obtained are shown below. However, hydroxyequol was acetylated and measured as hexaacetylhydroxyequol. Excor 1H-NMR (DMSO-d6) 5.75 (2
H, t), 5.82 (1H, d), 5.83 (1H
, t), 5.98 (1H, d), 6.16 (1H, s
), 9.17 (2H, s), 9.19 (1H, s)
, 9.20 (1H, s), 9.48 (1H, s),
9.53 (1H, s), 13C-NMR (DMSO
-d6) 160.4(s), 158.7(sx2
), 153.0(s), 146.1(s), 14
5.9(s), 142.7(s), 137.3(
s), 123.5(s), 122.6(s), 9
8.7(d), 98.4(d), 96.4(d),
94.0 (dx3) Hexaacetylhydroxyequol 1H-NMR (CDCl3) 1.73 (3H, s
), 1.99 (3H, s), 2.09 (3H, s)
, 2.21 (6H, s), 2.31 (3H, s),
6.53 (2H, d), 6.63 (1H, s),
6.67 (1H, t), 6.67 (1H, s), 1
3C-NMR (CDCl3) 168.6 (s),
168.55 (s), 168.2 (s), 168.
0(s), 166.6(s), 157.9(s),
151.6 (s), 144.3 (s), 141.3
(s), 139.3(s), 137.6(s),
136.4 (s), 134.8 (s), 132.9
(s), 131.9(s), 131.4(s),
114.6(s), 112.8(d) 110.2(
d) 108.7(d) 106.4(d), 21
．． 1(q), 20.7(q), 20.5(q),
20.4(q), 19.4(q) Tyrosinase inhibition test A 0.05% aqueous solution of each compound was used as a sample, and the following test procedure was conducted.
【００１６】チロシン（０．３ｍｇ／ｍｌ）を２０ｍｇ
、マッキルベイン緩衝液（ｐＨ６．８）を２０ｍｌ、寒
天を０．６ｇ三角フラスコに入れ、撹拌後、加熱沸騰さ
せてから冷却して４５℃になったとき、チロシナーゼ溶
液（１ｍｇ／ｍｌ）を０．２ｍｌ加え、撹拌後シャーレ
に移して寒天平板をつくり、試料を含浸させた直径１０
ｍｍのペーパーディスクを置いて、それを中心とした阻
止円径の大小を測定し、チロシナーゼ阻害効果を判定し
た。同時に、チロシナーゼ阻害効果の大きいことが知ら
れているコウジ酸、アルブチンについても対照として測
定した。結果を次の表１に示す。20mg of tyrosine (0.3mg/ml)
, 20 ml of McIlvaine buffer (pH 6.8) and 0.6 g of agar were placed in an Erlenmeyer flask, stirred, heated to boiling, and then cooled to 45°C. When the temperature reached 45°C, tyrosinase solution (1 mg/ml) was added to Add 2 ml, stir, and transfer to a Petri dish to make an agar plate.
A paper disk (mm) was placed, and the diameter of the inhibition circle centered on the disk was measured to determine the tyrosinase inhibitory effect. At the same time, kojic acid and arbutin, which are known to have a large tyrosinase inhibitory effect, were also measured as controls. The results are shown in Table 1 below.
【００１７】[0017]
【表１】[Table 1]
【００１８】＊２４時間経過後、水、アルブチン、コウ
ジ酸のペーパーディスクは黒褐色に変色していたが、エ
クコール及びヒドロキシエクコールのペーバーディスク
は白色のままであった。*After 24 hours, the water, arbutin, and kojic acid paper discs had turned blackish brown, but the equol and hydroxyequol paper discs remained white.
【００１９】また上記と同じ試料を使用し、チロシン溶
液（３０ｍｇ／２００ｍｌ）１０ｍｌ、マッキルベイン
緩衝液（ｐＨ６．８）１０ｍｌ、蒸留水２０ｍｌに、試
料を１ｍｌ加え、３７℃で１０分間インキュベートした
後、チロシナーゼ溶液（１５ｍｇ／１５ｍｌ、シグマ社
）を０．１ｍｌ投入し、スターラで撹拌しながら、６５
０ｎｍで３０分毎に吸光度を測定し、メラニンの生成を
測定した。アスコルビン酸とアルブチンを対照とした。
結果を下記表２に示す。Using the same sample as above, 1 ml of the sample was added to 10 ml of tyrosine solution (30 mg/200 ml), 10 ml of McIlvaine buffer (pH 6.8), and 20 ml of distilled water, and after incubation at 37° C. for 10 minutes, Add 0.1 ml of tyrosinase solution (15 mg/15 ml, Sigma), stir with a stirrer,
Absorbance was measured every 30 minutes at 0 nm to measure melanin production. Ascorbic acid and arbutin were used as controls. The results are shown in Table 2 below.
【００２０】[0020]
【表２】[Table 2]
【００２１】各試料について得られた吸光度を時間に対
してプロットしたグラフを第１図に示す。A graph in which the absorbance obtained for each sample is plotted against time is shown in FIG.
【００２２】上記結果から判るように、本発明の式Ｉの
化合物は、これまでチロシナーゼ阻害活性を有すること
が知られているコウジ酸、アルブチン等と比較して同等
以上のチロシナーゼ阻害活性を有するものであり、美白
化粧料、食品の黒変防止剤等に使用するのに極めて有用
である。As can be seen from the above results, the compound of formula I of the present invention has a tyrosinase inhibitory activity equivalent to or higher than that of kojic acid, arbutin, etc., which have been known to have tyrosinase inhibitory activity. Therefore, it is extremely useful for use in whitening cosmetics, anti-blackening agents for foods, etc.
【００２３】本発明のチロシナーゼ阻害剤を含む美白化
粧料は、従来使用されている化粧料基材を用いて常法に
より、クリーム、乳液、化粧水等の適当な形態で製造す
ることができる。また、該美白化粧料は、紫外線吸収剤
、紫外線散乱剤、その他の薬効成分、増粘剤、可塑剤、
着色料、香料等の任意の公知の添加物を含有することが
できる。The whitening cosmetic containing the tyrosinase inhibitor of the present invention can be produced in an appropriate form such as a cream, milky lotion, lotion, etc. by a conventional method using conventionally used cosmetic base materials. In addition, the whitening cosmetics include ultraviolet absorbers, ultraviolet scattering agents, other medicinal ingredients, thickeners, plasticizers,
Any known additives such as colorants and fragrances can be contained.
【００２４】本発明のチロシナーゼ阻害剤を美白化粧料
に使用する場合、化粧料１００ｇ当り上記一般式Ｉの化
合物を０．５〜１ｇ程度含むような量で使用するのが好
ましい。When the tyrosinase inhibitor of the present invention is used in whitening cosmetics, it is preferably used in an amount such that about 0.5 to 1 g of the compound of general formula I is contained per 100 g of the cosmetic.
【００２５】また、本発明のチロシナーゼ阻害剤を食品
の黒変防止剤に使用する場合には、上記一般式Ｉの化合
物の水溶液または適当な有機溶媒中の溶液として使用す
るのが好ましく、さらに任意の添加剤を含んでいてもよ
い。食品の黒変防止剤に使用する場合には、溶液１００
ｌ 当り上記一般式一の化合物を１〜２ｇ含むような量
で使用することが好ましい。When the tyrosinase inhibitor of the present invention is used as a blackening inhibitor for foods, it is preferably used as an aqueous solution of the compound of the above general formula I or as a solution in a suitable organic solvent. It may contain additives. When used as an anti-blackening agent for foods, solution 100
It is preferable to use an amount such that 1 to 2 g of the compound of the above general formula 1 is contained per 1 liter of the compound.
【００２６】[0026]
【実施例】実施例１
化粧水（油性）
ソルビトール（７０％）
３．０ｇグリセリン
５．０ｇエクコ
ール又はヒドロキシエクコール ０．２ｇ水
７０．０ｇこれらの成分を混合溶
解する。これに、アラントイン
０．１ｇポリオキシ
エチレン硬化ヒマシ油誘導体 ０．５ｇエタノール
２０．０ｇ香 料
適 量の混
合溶液を撹拌しながら加えて均一な溶液とし、皮膚美白
効果を有する化粧水を得る。[Example] Example 1 Lotion (oil-based) Sorbitol (70%)
3.0g glycerin
5.0g equol or hydroxyequol 0.2g water
Mix and dissolve 70.0g of these ingredients. In this, allantoin
0.1g polyoxyethylene hydrogenated castor oil derivative 0.5g ethanol
20.0g fragrance
Add an appropriate amount of the mixed solution while stirring to obtain a homogeneous solution to obtain a lotion having a skin whitening effect.
【００２７】実施例２
化粧水（乾性）
エチレングリコール
２．５ｇプロピレングリコール
５．０ｇシリコーン
０．
０００１ｇエクコール又はヒドロキシエクコール
０．１ｇ水
７０．０ｇこれ
らの成分を混合溶解する。これに、尿 素
１．０ｇポリオキシエチレンソルビタン
１．２ｇモノラウレート
エタノール
２０ｇε−アミノカプロン酸
０．１ｇ香 料
適 量実施例３
洗顔クリーム
グリセリン
２．０ｇステアリン酸
２０．０ｇ
ミリスチン酸
１０．０ｇラウリン酸
５．０ｇ
ポリオキシエチレンラウリルエーテル １．０
ｇエクコール又はヒドロキシエクコール ０．
５ｇ香料および防腐剤
適 量これらの成分を混合し、約７５
℃で加熱溶解し、これに、約７５℃に加熱した、
水酸化カリウム
５．５ｇ水
５６
．０ｇの溶液を撹拌しながら加えた後、冷却して皮膚美
白効果を有する洗顔クリームを得る。Example 2 Lotion (drying) Ethylene glycol
2.5g propylene glycol
5.0g silicone
0.
0001g Equol or Hydroxy Equol
0.1g water
Mix and dissolve 70.0g of these ingredients. In addition, urea
1.0g polyoxyethylene sorbitan
1.2g monolaurate ethanol
20gε-aminocaproic acid
0.1g fragrance
Appropriate amount Example 3 Facial cleansing cream glycerin
2.0g stearic acid
20.0g
myristic acid
10.0g lauric acid
5.0g
Polyoxyethylene lauryl ether 1.0
gequol or hydroxyequol 0.
5g fragrance and preservatives
Mix appropriate amounts of these ingredients and make approximately 75
Potassium hydroxide heated to about 75°C
5.5g water
56
．． After adding 0 g of the solution with stirring, it is cooled to obtain a facial cleansing cream with skin whitening effect.
【００２８】実施例４
パック
ポリビニルアルコール
１５．０ｇ防 腐 剤
０．１ｇ水
７５．０ｇエクコール又はヒドロ
キシエクコール ０．３ｇこれらの成分を混合
し、約８０℃で加熱溶解後、室温まで冷却し、
グリセリン
４．０ｇエタノール
５．０
ｇ香 料
適 量を混合して均一に溶
解し、パックを得る。Example 4 Packed polyvinyl alcohol
15.0g preservative
0.1g water
75.0g Equol or Hydroxyequol 0.3g Mix these ingredients, heat and dissolve at about 80°C, cool to room temperature, and prepare glycerin.
4.0g ethanol
5.0
g fragrance
Mix appropriate amounts and dissolve uniformly to obtain a pack.
【００２９】実施例５
油性クリーム
ミツロウ
１０．０ｇパラフィンワックス
６．０ｇラノ
リン
３．０ｇイソプロピルミリステート
６．０ｇスクワラン
８．０ｇ流動パラフィン
２５．０ｇエクコール又はヒ
ドロキシエクコール ０．５ｇポリオキシエチ
レンソルビタン １．８ｇモノス
テアレート
ソルビタンモノステアレート
４．２ｇ防 腐 剤
適 量これらの成分
を混合し、約７５℃で加熱溶解し、これに約７５℃に加
熱した、
プロピレングリコール
２．０ｇホ ウ 砂
０．７ｇ尿
素
５．０ｇ水
２８．０ｇの混合物を攪拌しながら加え、冷却した後
、５５℃で香料を適量加え、攪拌しながら４５℃まで冷
却し、放置して油性クリームを得る。Example 5 Oil-based cream beeswax
10.0g paraffin wax
6.0g lanolin
3.0g isopropyl myristate
6.0g squalane
8.0g liquid paraffin
25.0g equol or hydroxyequol 0.5g polyoxyethylene sorbitan 1.8g monostearate sorbitan monostearate
4.2g preservative
Mix appropriate amounts of these ingredients, heat and melt at about 75°C, and add propylene glycol heated to about 75°C.
2.0g Borax Sand
0.7g urine
Basic
5.0g water
Add 28.0 g of the mixture with stirring, and after cooling, add an appropriate amount of fragrance at 55°C, cool to 45°C while stirring, and leave to obtain an oily cream.
【００３０】実施例６
青果物褐黒変防止剤
水 ５００ｍｌにエクコール又はヒドロキシエクコール
０．５ｇを溶解し、これに皮をむいたリンゴを２分間
接触させた。対照区（接触させないもの）は５分後には
変色したが本発明のチロシナーゼ阻害剤からなる青果物
の褐黒変防止剤に接触させたリンゴは１５分後も変色は
認められなかった。Example 6 Fruit and vegetable browning prevention agent 0.5 g of equol or hydroxyequol was dissolved in 500 ml of water, and a peeled apple was brought into contact with the solution for 2 minutes. The control group (no contact) changed color after 5 minutes, but the apples that were brought into contact with the agent for preventing browning of fruits and vegetables consisting of the tyrosinase inhibitor of the present invention did not change color even after 15 minutes.
【００３１】実施例７
魚介類黒褐変防止剤
Ｌ−アスコルビン酸
３．０ｇ乳 糖
６５．０ｇ
エクコール又はヒドロキシエクコール ０．５
ｇソルビトール
６．０ｇＬ−アスコルビン酸ナトリ
ウム ２０．０ｇミョウバン
５．５ｇの混合物を ５００〜１０００ｍｌの水また
は海水に溶かし、魚介類を５〜１０分間浸漬させること
により魚介類の黒褐変を抑制させる。Example 7 Seafood browning inhibitor L-ascorbic acid
3.0g lactose
65.0g
Equol or Hydroxyequol 0.5
g-Sorbitol
6.0gL-sodium ascorbate 20.0g alum
Dissolve 5.5 g of the mixture in 500-1000 ml of water or seawater and soak the seafood for 5-10 minutes to suppress browning of the seafood.
【図１】 第１図は、本発明のチロシナーゼ阻害剤の
チロシナーゼ阻害効果を表すグラフである。FIG. 1 is a graph showing the tyrosinase inhibitory effect of the tyrosinase inhibitor of the present invention.
Claims (3)
有する化合物を活性成分とするチロシナーゼ阻害剤。1. A tyrosinase inhibitor comprising, as an active ingredient, a compound having the following general formula I: wherein R represents a hydrogen atom or a hydroxyl group.
阻害剤。2. The tyrosinase inhibitor according to claim 1, which contains a compound of formula 2 as an active ingredient.
阻害剤。3. The tyrosinase inhibitor according to claim 1, which comprises a compound of the formula: [Image Omitted] as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3002021A JPH04235110A (en) | 1991-01-11 | 1991-01-11 | Tyrosinase-inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3002021A JPH04235110A (en) | 1991-01-11 | 1991-01-11 | Tyrosinase-inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04235110A true JPH04235110A (en) | 1992-08-24 |
Family
ID=11517680
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3002021A Pending JPH04235110A (en) | 1991-01-11 | 1991-01-11 | Tyrosinase-inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04235110A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010098533A3 (en) * | 2009-02-26 | 2010-10-21 | 부경대학교 산학협력단 | Ecklonia cava extract with skin whitening activity |
| JP2013133314A (en) * | 2011-12-27 | 2013-07-08 | Tropical Plant Resources Institute Inc | Tyrosinase activity inhibitor, bleaching cosmetic, external preparation for skin and browning inhibitor for food |
-
1991
- 1991-01-11 JP JP3002021A patent/JPH04235110A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010098533A3 (en) * | 2009-02-26 | 2010-10-21 | 부경대학교 산학협력단 | Ecklonia cava extract with skin whitening activity |
| JP2013133314A (en) * | 2011-12-27 | 2013-07-08 | Tropical Plant Resources Institute Inc | Tyrosinase activity inhibitor, bleaching cosmetic, external preparation for skin and browning inhibitor for food |
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