JP4239126B2 - Tyrosinase activity inhibitor - Google Patents
Tyrosinase activity inhibitor Download PDFInfo
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- JP4239126B2 JP4239126B2 JP34722599A JP34722599A JP4239126B2 JP 4239126 B2 JP4239126 B2 JP 4239126B2 JP 34722599 A JP34722599 A JP 34722599A JP 34722599 A JP34722599 A JP 34722599A JP 4239126 B2 JP4239126 B2 JP 4239126B2
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- Prior art keywords
- tyrosinase activity
- activity inhibitor
- tyrosinase
- skin
- inhibitor
- 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
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- Coloring Foods And Improving Nutritive Qualities (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【0001】
【発明の属する技術分野】
本発明は、チロシナーゼ活性阻害剤およびそのチロシナーゼ活性阻害剤を含有する皮膚外用剤と食品褐変防止剤に関するものである。
【0002】
【従来の技術】
チロシナーゼは、種々のカテコール誘導体を基質とする酸化酵素である。そのほとんどがモノフェノールモノオキシゲナーゼ活性を有し、モノフェノールを基質として、オルト−ジフェノールを生じ、さらにオルト−キノン類に酸化する。この酸化酵素は広く自然界に分布し、キノコやジャガイモ、リンゴなどの植物、動物の色素細胞に存在する。動物中の酸化酵素は、特にチロシン、ドーパに対して高い活性を示し、メラニンの生合成に深く関与する。メラニンは、チロシン→L−ドーパ→ドーパキノン→ドーパクロム→5,6ジヒドロキシインドール→インドール−5,6−キノン→メラニンの過程を経て生成され、チロシナーゼは、チロシン→L−ドーパ→ドーパキノンの酸化過程に関与している。メラニンは毛髪や肌の色を決定している色素である。この色素は、皮膚では表皮基底層に存在するメラノサイトにおいて、光や紫外線に反応して生成される。皮膚におけるメラニン生成は、紫外線等による悪影響から人間を防御する役目を担っている。しかしながら、大量に光や紫外線を浴びるなどの刺激があると、メラニン生成機能が局部的に持続し、その部分の皮膚が黒化してしまう。その結果、色素が沈着するなど、しみ・そばかすを形成して、やがては皮膚の老化を促進してしまう。また、リンゴやヤマイモ、レタスなどの野菜・果物を切断すると、切断面が褐色変化する現象もメラニン色素が関与している。切断面が褐変した青果物は、商品価値が低下して長期間保存することは困難である。美白を促進したり、食品の褐変化を防止する目的で、従来、チロシナーゼの活性阻害剤が使用されてきている。チロシナーゼの活性阻害剤としては、例えば、ビタミンC(特開平2−45408号公報等)、アルブチン、植物などから抽出されたエキス(特開平6−40896号公報等)、および亜硫酸塩類などが知られている。しかしながら、ビタミンCは自身の還元作用から酸化されやすく不安定で、保存上の問題がある。また、アルブチンは、耐熱安定性などに問題があり、これも取扱い上の問題がある。植物抽出物は、化学組成の同定が難しく、ロット間での品質のばらつきが懸念されている。亜硫酸塩類は、人体への皮膚刺激性が認められ、安全上の問題がある。一方、食品香料として用いられている芳香族アルデヒド類に、チロシナーゼ阻害活性を持つものが知られているが(油化学、43(7)、574〜578、1994年等)、それ自体のもつ色調によって食品等を着色してしまうなどの問題がある。
【0003】
【発明が解決しようとする課題】
本発明の目的は、人体への安全性が高く、耐熱性などの安定性に優れ、着色などの問題がない、純度の高いチロシナーゼ活性阻害剤を提供することにある。本発明者らは上記課題を解決するために鋭意検討を行なった結果、4−メトキシフェネチルメチルエーテルおよびフェニルアセトアルデヒドに高いチロシナーゼ活性阻害効果を持つことを見い出し本発明に至った。
【0004】
【課題を解決するための手段】
本発明のチロシナーゼ活性阻害剤は、4−メトキシフェネチルメチルエーテルおよびフェニルアセトアルデヒドの少なくとも一つを有効成分として含有するチロシナーゼ活性阻害剤である。
【0005】
また、本発明の皮膚外用剤は、前記のチロシナーゼ活性阻害剤を含有する皮膚外用剤である。
【0006】
また、本発明の食品褐変防止剤は、前記のチロシナーゼ活性阻害剤を含有する食品褐変防止剤である。
【0007】
【発明の実施の形態】
本発明で用いられるチロシナーゼ活性阻害効果を持つ上記の化合物は、チロシナーゼ活性阻害作用を持つことから、メラニン生成抑制を作用機序とする化粧品、医薬品、医薬部外品、外用薬、食品、食品添加物および飼料等に、従来のチロシナーゼ活性阻害剤と同様に利用可能であり、特に皮膚外用剤および食品褐変防止剤に好適に用いられる。また、本発明のチロシナーゼ活性阻害剤は、従来のチロシナーゼ活性阻害剤と併用することが可能である。
【0008】
本発明のチロシナーゼ活性阻害剤の適用量は、目的や用途等によるが、通常0.001〜10重量%であり、好ましくは0.01〜1重量%程度である。
【0009】
本発明のチロシナーゼ活性阻害剤は、皮膚外用剤に好適である。本発明のチロシナーゼ活性阻害剤を皮膚外用剤として利用する場合の剤型としては、クリーム、乳液、ファウンデーション、パック、ローション、ゲル状、溶液状およびスティック状等がある。
【0010】
また、これらには適宜の成分、例えば、油剤、保湿剤、増粘剤、防腐剤、乳化剤、顔料、pH調製剤、他の薬効成分、紫外線吸収剤および香料等など一般に用いられる各種成分を配合することもできる。
【0011】
また、本発明のチロシナーゼ活性阻害剤は、食品等に好適である。本発明のチロシナーゼ活性阻害剤を食品等に適用する場合は、野菜や果物等の青果物の切断面に適当量を噴霧、塗布あるいは浸漬すればよい。
【0012】
【実施例】
以下、試験例および実施例によって本発明によるチロシナーゼ活性阻害効果を明らかにするが、本発明はこれらに限定されるものではない。
【0013】
【実施例1】
(試験例1、2、比較例1、2)
チロシナーゼ活性阻害試験測定原理は、L−ドーパにチロシナーゼを作用させて生成するドーパクロムを測定するものである。1%Tween80を含む10mMリン酸緩衝液(pH6.8)2.7mlに1200ユニット/mlのチロシナーゼ(SIGMA社製)溶液0.1mlとジメチルスルフォキシド(以下DMSO)に適宜希釈した表1の各香料化合物0.2mlをそれぞれ混合して、30℃で10分間インキュベートした。次いで、10mML−ドーパ溶液1mlを加えて30℃で10分間インキュベートした後、アジ化ナトリウムを加えて酵素反応を停止し、475nmにおける吸光度を測定した。チロシナーゼ活性阻害の効果は、以下の式により算出し、表1に示した。
{[(B−Bc)−(S−Sc)]/(B−Bc)}×100(%)
S:サンプル添加時の吸光度Sc:サンプル添加時の比較対照として、酵素溶液の代わりにリン酸緩衝液を加えて同様の操作をしたときの吸光度。
B:サンプルの代わりにDMSOを加えて同様に操作した時の吸光度。
Bc:サンプルの代わりにDMSOを、酵素の代わりにリン酸緩衝液を加えて同様に操作した時の吸光度。
【0014】
この結果、表1に示すように4−メトキシフェネチルメチルエーテルおよびフェニルアセトアルデヒドは、既知のチロシナーゼ活性阻害剤であるオイゲノールやコウジ酸に比べてチロシナーゼ活性阻害効果が高いことが示された。
【0015】
【表1】
【0016】
【実施例2】
下記表2の組成の乳液は、常法に従い、下表の(1)と(2)をそれぞれ80℃に加熱溶解し、撹拌しながら(2)を(1)に徐々に加えて乳化して調製した。
【0017】
【表2】
【0018】
得られた乳液は、美白作用に優れ、しっとりした使用感のものであった。また、保存安定性にも優れていた。
【0019】
【実施例3】
下記表3の組成のクリームは、常法に従い、下表の(1)と(2)をそれぞれ80℃に加熱溶解し、撹拌しながら(2)を(1)に徐々に加えて乳化し、35℃まで冷却して調製した。
【0020】
【表3】
【0021】
得られたクリームは美白作用に優れ、しっとりした使用感のものであった。また、耐熱性もあり保存安定性にも優れていた。
【0022】
【発明の効果】
以上記載のごとく、本発明のチロシナーゼ活性阻害剤は、その構成成分が既に香料として一般的に使用されていて安全性も高いことから、皮膚外用剤や食品・食品添加物として用いても人体に対する副作用の心配がない。しかも、本発明で用いられる化合物は、低濃度で高いチロシナーゼ活性阻害効果を有するが、これらを、紫外線などによるメラニンの過剰生成の結果形成されるシミ・ソバカスや色素沈着を予防する化粧品等皮膚外用剤への配合や、食品の褐色変化の防止への利用が可能なチロシナーゼ活性阻害剤として提供することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a tyrosinase activity inhibitor, a skin external preparation containing the tyrosinase activity inhibitor and a food browning inhibitor.
[0002]
[Prior art]
Tyrosinase is an oxidase that uses various catechol derivatives as substrates. Most of them have monophenol monooxygenase activity, and mono-phenol is used as a substrate to produce ortho-diphenol, which is further oxidized to ortho-quinones. This oxidase is widely distributed in nature, and is present in pigment cells of plants and animals such as mushrooms, potatoes and apples. Oxidases in animals exhibit high activity especially against tyrosine and dopa, and are deeply involved in melanin biosynthesis. Melanin is produced through the process of tyrosine->L-dopa->dopaquinone->dopachrome-> 5,6 dihydroxyindole->indole-5,6-quinone-> melanin, and tyrosinase is involved in the oxidation process of tyrosine->L-dopa-> dopaquinone is doing. Melanin is a pigment that determines the color of hair and skin. In the skin, this pigment is produced in response to light and ultraviolet rays in melanocytes existing in the basal layer of the epidermis. Melanin production in the skin plays a role in protecting humans from the adverse effects of ultraviolet rays and the like. However, when there is a stimulus such as exposure to a large amount of light or ultraviolet rays, the melanin generating function is locally maintained, and the skin of that part is darkened. As a result, pigmentation will form spots and freckles, which eventually promote skin aging. Melanin pigment is also involved in the phenomenon that the cut surface changes brown when vegetables and fruits such as apples, yams, and lettuce are cut. Fruits and vegetables whose cut surfaces are browned are difficult to store for a long period of time due to their reduced commercial value. Conventionally, tyrosinase activity inhibitors have been used for the purpose of promoting whitening and preventing browning of food. Examples of tyrosinase activity inhibitors include vitamin C (JP-A-2-45408, etc.), arbutin, extracts extracted from plants (JP-A-6-40896, etc.), and sulfites. ing. However, vitamin C is easily oxidized due to its own reducing action and is unstable, and has a storage problem. Arbutin also has a problem in heat resistance stability, which also has a problem in handling. Plant extracts are difficult to identify in chemical composition, and there is a concern about quality variations among lots. Sulfites are recognized as a skin irritation to the human body and have safety problems. On the other hand, aromatic aldehydes used as food fragrances are known to have tyrosinase inhibitory activity (Oil Chemistry, 43 (7), 574-578, 1994, etc.). There are problems such as coloring foods and the like.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a highly pure tyrosinase activity inhibitor having high safety to the human body, excellent stability such as heat resistance, and no problems such as coloring. The present inventors have reached the finding present invention to have an extensive study to perform a result, 4-methoxy-phenethyl methyl ether and phenyl acetaldehyde high tyrosinase activity inhibition effect in order to solve the above problems.
[0004]
[Means for Solving the Problems]
Tyrosinase activity inhibitor of the present invention is a tyrosinase activity inhibitor comprising as an 4-methoxy phenethyl methyl ether and at least one active ingredient of phenylacetaldehyde.
[0005]
Moreover, the skin external preparation of this invention is a skin external preparation containing the said tyrosinase activity inhibitor .
[0006]
Moreover, the food browning prevention agent of this invention is a food browning prevention agent containing the said tyrosinase activity inhibitor .
[0007]
DETAILED DESCRIPTION OF THE INVENTION
Since the above-mentioned compound having an inhibitory effect on tyrosinase activity used in the present invention has an inhibitory action on tyrosinase activity, cosmetics, pharmaceuticals, quasi-drugs, topical drugs, foods, foods with melanin production suppression mechanism the additive and fodder, etc., are available as in the conventional tyrosinase activity inhibitor, it is suitably used particularly skin external agent and food browning inhibitor. Moreover, the tyrosinase activity inhibitor of this invention can be used together with the conventional tyrosinase activity inhibitor.
[0008]
Dosage of tyrosinase activity inhibitor of the present invention, depending on the purpose, application, and the like, is usually 0.001 to 10% by weight, preferably about 0.01 to 1% by weight.
[0009]
The tyrosinase activity inhibitor of the present invention is suitable for an external preparation for skin. Examples of dosage forms when the tyrosinase activity inhibitor of the present invention is used as an external preparation for skin include creams, emulsions, foundations, packs, lotions, gels, solutions, and sticks.
[0010]
The compounding these include appropriate components, for example, oils, humectants, thickeners, preservatives, emulsifiers, pigments, pH adjusting agent, other medicinal ingredients, various components commonly used such as UV absorbers and perfumes You can also
[0011]
Moreover, the tyrosinase activity inhibitor of this invention is suitable for foodstuffs etc. When the tyrosinase activity inhibitor of the present invention is applied to foods or the like, an appropriate amount may be sprayed, applied or immersed on the cut surface of fruits and vegetables such as vegetables and fruits.
[0012]
【Example】
Hereinafter, although the tyrosinase activity inhibitory effect by this invention is clarified by a test example and an Example, this invention is not limited to these.
[0013]
[Example 1]
(Test Examples 1 and 2 and Comparative Examples 1 and 2)
The tyrosinase activity inhibition test measurement principle is to measure dopachrome produced by the action of tyrosinase on L-dopa. Table 1 was appropriately diluted in 2.7 ml of 10 mM phosphate buffer (pH 6.8) containing 1% Tween 80 in 0.1 ml of 1200 unit / ml tyrosinase (manufactured by SIGMA) and dimethyl sulfoxide (hereinafter DMSO). Each fragrance compound (0.2 ml) was mixed and incubated at 30 ° C. for 10 minutes. Subsequently, 1 ml of 10 mM L-dopa solution was added and incubated at 30 ° C. for 10 minutes, and then the enzyme reaction was stopped by adding sodium azide, and the absorbance at 475 nm was measured. The effect of inhibiting tyrosinase activity was calculated by the following formula and shown in Table 1.
{[(B-Bc)-(S-Sc)] / (B-Bc)} × 100 (%)
S: Absorbance at the time of sample addition Sc: Absorbance when the same operation was performed by adding a phosphate buffer instead of the enzyme solution as a comparative control at the time of sample addition.
B: Absorbance when DMSO was added instead of the sample and the same operation was performed.
Bc: Absorbance when the same operation was performed by adding DMSO instead of the sample and phosphate buffer instead of the enzyme.
[0014]
As a result, Table 1 as shown in 4 - methoxyphenethyl methyl ether Contact and phenyl acetaldehyde arsenide de, it showed high tyrosinase activity inhibition effect compared to eugenol and kojic acid is known tyrosinase activity inhibitor .
[0015]
[Table 1]
[0016]
[Example 2 ]
The emulsions having the composition shown in Table 2 below are prepared by dissolving (1) and (2) in the following table at 80 ° C., respectively, and gradually adding (2) to (1) while stirring to emulsify. Prepared.
[0017]
[Table 2 ]
[0018]
The obtained emulsion was excellent in whitening action and had a moist feeling of use. In addition, the storage stability was excellent.
[0019]
[Example 3 ]
The creams having the composition shown in Table 3 are emulsified by dissolving (1) and (2) in the following table by heating to 80 ° C., respectively, and gradually adding (2) to (1) while stirring according to a conventional method. Prepared by cooling to 35 ° C.
[0020]
[Table 3 ]
[0021]
The obtained cream was excellent in whitening action and had a moist use feeling. It also had heat resistance and excellent storage stability .
[0022]
【The invention's effect】
As described above, the tyrosinase activity inhibitor of the present invention has high safety because its constituents are already commonly used as fragrances, so even if used as a skin external preparation or food / food additive, There is no worry about side effects. In addition, the compounds used in the present invention have a high tyrosinase activity inhibitory effect at a low concentration. However, these are applied to the skin or the like for preventing skin spots, freckles and pigmentation formed as a result of excessive production of melanin by ultraviolet rays or the like. It can be provided as a tyrosinase activity inhibitor that can be incorporated into an agent or used to prevent browning of food.
Claims (2)
Priority Applications (1)
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JP34722599A JP4239126B2 (en) | 1999-12-07 | 1999-12-07 | Tyrosinase activity inhibitor |
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JP34722599A JP4239126B2 (en) | 1999-12-07 | 1999-12-07 | Tyrosinase activity inhibitor |
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JP2001163719A JP2001163719A (en) | 2001-06-19 |
JP4239126B2 true JP4239126B2 (en) | 2009-03-18 |
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JP34722599A Expired - Lifetime JP4239126B2 (en) | 1999-12-07 | 1999-12-07 | Tyrosinase activity inhibitor |
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Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
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JP4657778B2 (en) * | 2004-03-30 | 2011-03-23 | 曽田香料株式会社 | Arachidonic acid metabolism inhibitor |
JP4657653B2 (en) * | 2004-08-24 | 2011-03-23 | 曽田香料株式会社 | Body temperature raising agent |
JP5783612B2 (en) * | 2010-02-24 | 2015-09-24 | 国立大学法人北海道大学 | Maillard reaction inhibitor, α-dicarbonyl compound decomposing agent, and Maillard reaction suppression method |
JP6285352B2 (en) * | 2012-03-26 | 2018-02-28 | 飯沼 宗和 | 3-Decenoic acid derivatives and uses thereof |
WO2014077334A1 (en) | 2012-11-15 | 2014-05-22 | 株式会社資生堂 | Melanin production inhibitor |
JP5536913B2 (en) * | 2013-01-10 | 2014-07-02 | 曽田香料株式会社 | Platelet aggregation inhibitor |
JP7390844B2 (en) * | 2019-10-07 | 2023-12-04 | 花王株式会社 | Anti-browning agent for leafy vegetables |
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1999
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