JP2009227612A - Tyrosinase activity inhibitor and bleaching cosmetic containing the same - Google Patents

Tyrosinase activity inhibitor and bleaching cosmetic containing the same Download PDF

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JP2009227612A
JP2009227612A JP2008075603A JP2008075603A JP2009227612A JP 2009227612 A JP2009227612 A JP 2009227612A JP 2008075603 A JP2008075603 A JP 2008075603A JP 2008075603 A JP2008075603 A JP 2008075603A JP 2009227612 A JP2009227612 A JP 2009227612A
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plant
tyrosinase activity
activity inhibitor
inhibitor according
tyrosinase
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JP5472563B2 (en
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Tetsuya Toyokawa
哲也 豊川
Masaaki Teruya
正映 照屋
Toshio Ichiba
俊雄 市場
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Okinawa Prefectural Government
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Abstract

<P>PROBLEM TO BE SOLVED: To develop a new tyrosinase activity inhibitor having high safety while having excellent activity. <P>SOLUTION: The tyrosinase activity inhibitor contains a plant extract of a plant selected from the group consisting of plants of Sapotaceae, Myrtaceae, Rubiaceae, Plumbaginaceae, Rhizophoraceae, Ebenaceae, Moraceae, Primulaceae, Combretaceae, Zingiberaceae, Balanophoraceae, Camelliaceae, Euphorbiaceae, Sonneratiaceae, Amaryllidaceae, Sapindaceae, Casuarinaceae and Liliaceae as an active ingredient. The external preparation for the skin and the cosmetic contain the inhibitor as an active ingredient. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

本発明は、チロシナーゼ活性阻害剤に関し、更に詳細には、メラニン生成に関係するチロシナーゼを効果的に阻害するチロシナーゼ活性阻害剤およびこれを利用する美白化粧料に関する。   The present invention relates to a tyrosinase activity inhibitor, and more particularly to a tyrosinase activity inhibitor that effectively inhibits tyrosinase related to melanin production and a whitening cosmetic using the same.

現在、皮膚の日焼けや、シミ、そばかす等を防ぐ目的で、数多くの美白化粧料が市販されている。これらの美白化粧料には、色素物質であるメラニンの生成を防ぐ成分が含まれているが、その多くは、メラニン生成の律速酵素であるチロシナーゼを阻害するチロシナーゼ活性阻害物質である。   Currently, many whitening cosmetics are on the market for the purpose of preventing sunburn, spots, freckles and the like on the skin. These whitening cosmetics contain components that prevent the production of melanin, which is a pigment substance, and many of them are tyrosinase activity inhibitors that inhibit tyrosinase, which is the rate-limiting enzyme for melanin production.

このチロシナーゼ活性阻害物質の代表的なものとしては、コウジ酸やアルブチン等が知られている。このうちコウジ酸は、コウジカビの培養発酵物中に生産されるものであり、そのチロシナーゼ阻害活性は高いが、経口摂取による発癌性の報告や、白血球減少作用等の副作用の報告もあり、安全性が十分に確保されているとは言い難い。また、アルブチンは、ウワウルシやコケモモの抽出物中から得ることができる化合物で、安全性はほぼ確認されているものであるが、そのチロシナーゼ阻害活性は、コウジ酸に比べ弱いという問題があった。   As typical tyrosinase activity inhibitors, kojic acid, arbutin and the like are known. Of these, kojic acid is produced in the fermentation product of Aspergillus oryzae, and its tyrosinase inhibitory activity is high, but there are reports of carcinogenicity by oral ingestion and side effects such as leukocyte reduction, etc. It is hard to say that is sufficiently secured. Arbutin is a compound that can be obtained from an extract of walnut and bilberry, and its safety has been almost confirmed. However, there is a problem that its tyrosinase inhibitory activity is weaker than that of kojic acid.

更に、上記以外の植物から得たチロシナーゼ活性阻害成分を得た報告もなされているが(特許文献1〜6等)、より優れた、新たなチロシナーゼ活性阻害成分の提供に関する要望は依然として強いものがあった。
特開平5−294819号 特開平6−305978号 特開平10−114670号 特開2003−55189 特開2006−176420 特開2006−69954
Furthermore, although reports on obtaining tyrosinase activity-inhibiting components obtained from plants other than the above have been made (Patent Documents 1 to 6 and the like), there is still a strong demand for providing new tyrosinase activity-inhibiting components. there were.
JP-A-5-294819 JP-A-6-305978 JP 10-114670 A JP 2003-55189 A JP 2006-176420 A JP 2006-69954 A

本発明は、優れた活性を有しながら安全性の高い、新しいチロシナーゼ活性阻害剤を提供することを、その課題とするものである。   An object of the present invention is to provide a novel tyrosinase activity inhibitor having excellent activity and high safety.

本発明者らは、沖縄県の植物資源に着目し、チロシナーゼ阻害活性を有するものについて鋭意検索を行ったところ、いくつかの植物は優れたチロシナーゼ阻害活性を有することを見出し、本発明を完成した。   The inventors of the present invention focused on the plant resources of Okinawa Prefecture and conducted an extensive search for those having tyrosinase inhibitory activity. As a result, they found that some plants have excellent tyrosinase inhibitory activity and completed the present invention. .

すなわち本発明は、アカテツ科植物、フトモモ科植物、アカネ科植物、イソマツ科植物、ヒルギ科植物、カキノキ科植物、クワ科植物、サクラソウ科植物、シクンシ科植物、ショウガ科植物、ツチトリモチ科植物、ツバキ科植物、トウダイグサ科植物、ハマザクロ科植物、ヒガンバナ科植物、ムクロジ科植物、モクマオウ科植物およびユり科植物よりなる群より選ばれた植物の抽出物を有効成分とするチロシナーゼ活性阻害剤である。   In other words, the present invention relates to acetaceae plant, myrtaceae plant, rhododendron plant, isopaceae plant, hirugaceae plant, oyster plant plant, mulberry plant, primrose plant, succulent plant plant, ginger plant, camellia plant, camellia plant It is a tyrosinase activity inhibitor comprising as an active ingredient an extract of a plant selected from the group consisting of genus plants, Euphorbiaceae plants, Hamasaeaceae plants, Amaryllidaceae plants, Mucrodiaceae plants, euphorbiaceae plants, and Lilium plants.

また本発明は、上記チロシナーゼチロシナーゼ活性阻害剤を含有する皮膚外用剤および美白化粧料である。   Moreover, this invention is the skin external preparation and whitening cosmetics containing the said tyrosinase tyrosinase activity inhibitor.

本発明のチロシナーゼ活性阻害剤の有効成分である沖縄県に生育する植物の抽出物は、優れたチロシナーゼ阻害活性を有し、しかも安全性が高いものである。   An extract of a plant growing in Okinawa which is an active ingredient of the tyrosinase activity inhibitor of the present invention has excellent tyrosinase inhibitory activity and high safety.

従って、本発明のチロシナーゼ活性阻害剤は、美白成分として、皮膚外用剤、美白化粧料などに利用することができるものである。   Therefore, the tyrosinase activity inhibitor of the present invention can be used as a whitening component in a skin external preparation, a whitening cosmetic, or the like.

本発明のチロシナーゼ活性阻害剤の有効成分は、アカテツ科植物、フトモモ科植物、アカネ科植物、イソマツ科植物、ヒルギ科植物、カキノキ科植物、クワ科植物、サクラソウ科植物、シクンシ科植物、ショウガ科植物、ツチトリモチ科植物、ツバキ科植物、トウダイグサ科植物、ハマザクロ科植物、ヒガンバナ科植物、ムクロジ科植物、モクマオウ科植物またはユり科植物(以下、「被抽出植物」という)を抽出処理に付すことにより得られる抽出物である。   The active ingredient of the tyrosinase activity inhibitor of the present invention includes: Acateaceae plant, Myrtaceae plant, Rubiaceae plant, Rubiaceae plant, Hygienidae plant, Oysteraceae plant, Mulberry plant, Primrose plant, Cyclicaceae plant, Ginger family Subjecting an extraction process to a plant, an aceae plant, an camellia plant, an euphorbiaceae plant, an azalea family plant, an amaryllidaceae plant, a mud crab family plant, an oleander plant or a lily family plant (hereinafter referred to as “extracted plant”) Is an extract obtained by

この被抽出植物のうち、アカテツ科植物としては、カニステル(Lucuma nervosa A.DC.)、サポジラ(Manilkara zapota(L.)P.van Royen)等を挙げることができ、カニステルの場合はその葉を、サポジラの場合はその実を利用することが好ましい。   Among the plants to be extracted, examples of the Acetaceae plant include canister (Lucuma nervosa A.DC.), sapodilla (Manilkara zapota (L.) P.van Royen), etc. In the case of a sapodilla, it is preferable to use the fruit.

フトモモ科植物としては、オオフトモモ(Syzygium samarangense Merr.&Perry.)、レモンユーカリ(Eucalyptus citriodora Hook)、アデク(Syzygium buxifolium)等を挙げることができ、何れもその葉を利用することが好ましい。   Examples of the myrtaceae plant include Syzygium samarangense Merr. & Perry. Lemon Eucalyptus (Eucalyptus citriodora Hook), Adek (Syzygium buxifolium) and the like.

アカネ科植物としては、ボチョウジ(Psychotria rubra)、ベニデマリ(Ixora coccinea L.)等を挙げることができ、このうち、ホチョウジはその葉を、ベニデマリは、葉や花を利用することが好ましい。   Examples of the Rubiaceae plant include Bosoji (Psychotria rubra), Benidemari (Ixora coccinea L.), etc. Among them, it is preferable to use the leaves of the red clover, and the leaves and flowers of Benidomari.

イソマツ科植物としては、ウスジロイソマツ(Limonium wrightii(Hance)O.Kuntze f.albo-lutescens Hatsusima)、ウコンイソマツ(Limonium wrightii(Hance)O.Kuntze f.wrightii)等を挙げることができ、このうちウスジロイソマツとしては、その地上部を、ウコンイソマツとしては、その根茎を利用することが好ましい。   Examples of the Iroaceae plant include the Japanese white pine (Limonium wrightii (Hance) O. Kuntze f. Albo-lutescens Hatsusima) and the turmeric islet (Limonium wrightii (Hance) O. Kuntze f. Wrightii). It is preferable to use the above-ground part as a white pine pine and the rhizome as a turmeric pine.

ヒルギ科植物としては、アカバナヒルギ(オヒルギ;Bruguiera gymnorrhiza)、メヒルギ(Kandelia candel(L.)Druce)等が挙げられ、アカバナヒルギとしては、その花や実を、メヒルギとしては、その葉を利用することが好ましい。   Examples of the family Hygiaceae include red guinea pig (Bruguiera gymnorrhiza), Japanese leeches (Kandelia candel (L.) Druce), etc. It is preferable.

カキノキ科植物としては、リュウキュウコクタン(Diospyros ferra var.buxifolia Bakh)等が、クワ科植物としては、パラミツ(Artocarpus heterophyllus Lam.)等がそれぞれ挙げられ、いずれもその葉を利用することが好ましい。   Examples of cynoaceae plants include Ryukyu Kokutan (Diospyros ferra var. Buxifolia Bakh), and examples of mulberry family plants include jackfruit (Artocarpus heterophyllus Lam.). It is preferable to use the leaves of each.

サクラソウ科植物としては、ハマボッス(Lysimachia mauritiana Lam.)等が挙げられ、その全草を利用することが好ましく、シクンシ科植物としては、ヒルギモドキ(Lumnitzera racemosa Willd.)等が挙げられ、その葉を利用することが好ましい。   Examples of primroses include hamabos (Lysimachia mauritiana Lam.), Preferably using the whole plant. Examples of ciraceae (Lumnitzera racemosa Willd.) Include leaves. It is preferable to do.

ショウガ科植物としては、ゲットウ(Alpinia speciosa(Wendl.)K.Schum)等が挙げられ、その花を利用することが好ましく、ツチトリモチ科植物としては、リュウキュウツチトリモチ(Balanophora kuroiwai Makino)等が挙げられ、その葉を利用することが好ましい。   Ginger (Alpinia speciosa (Wendl.) K. Schum) etc. are mentioned as a ginger family plant, It is preferable to utilize the flower, and Ryukyu Uchitorimochi (Balanophora kuroiwai Makino) etc. are mentioned as a plant family It is preferable to use the leaves.

ツバキ科植物としては、リュウキュウナガエヒサカキ(Adinandra ryukyuensis)等が挙げられ、その葉を利用することが好ましく、トウダイグサ科植物としては、アカギ(Bischofia javanica Bl.)等が挙げられ、その実を利用することが好ましい。   Examples of camellia plants include Adinandra ryukyuensis and the like, and it is preferable to use the leaves thereof, and examples of Euphorbiaceae plants include red chrysanthemum (Bischofia javanica Bl.) And the like are used. It is preferable.

ハマザクロ科植物としては、マヤプシキ(Sonneratia alba)等が、ヒガンバナ科植物としては、ハマユウ(Crinum asiaticum L. var japonicum aker)等が挙げられ、共にその葉を利用することが好ましい。   An example of the genus Acanthaceae is Mayopushiki (Sonneratia alba) and the like, and an example of the Amaryllidaceae plant is Craneum (Crinum asiaticum L. var japonicum aker), both of which preferably use the leaves.

ムクロジ科植物としては、タイワンモクゲンジ(Koelreuteria elegance A.C.Sm. Var.formosana F.G.Meyer)等が、モクマオウ科植物としては、モクマオウ(Casuarina equisetifolia J.R.et .G.Forst)等が挙げられ、共にそれらの葉を利用することが好ましい。   For example, for example, Koelreuteria elegance ACSm. Var.formosana FGMeyer, etc., for example, and for example, for example, for example, for example, Okuma (Casuarina equisetifolia JRet.G.Forst). It is preferable to use it.

ユリ科植物としては、ハマサルトリイバラ(Smilax sebeana Miq.)等が挙げられ、その地上部を利用することが好ましい。   Examples of the liliaceae plant include the smeltax rose (Smilax sebeana Miq.) And the like, and it is preferable to use the above-ground part.

上記被抽出植物に対する抽出溶媒としては、水やエタノール等の低級アルコールが挙げられるが、水−低級アルコールの混液、特に水とエタノールの混液が好ましい。   Examples of the extraction solvent for the plant to be extracted include lower alcohols such as water and ethanol, and a mixed solution of water and lower alcohol, particularly a mixture of water and ethanol is preferable.

上記被抽出植物の抽出処理は、例えば、当該植物の葉、花、根茎、地上部あるいは全草を乾燥させた後、これを切断ないし粉砕し、これにその5ないし20重量倍の抽出溶媒を加え、室温ないし100℃、好ましくは30ないし50℃で、12ないし150時間、好ましくは、24ないし48時間浸漬することにより行われる。この抽出に当たっては、振蕩撹拌ないしは機械撹拌することが好ましい。   The extraction process of the plant to be extracted includes, for example, drying leaves, flowers, rhizomes, aerial parts or whole plants of the plant, then cutting or crushing them, and adding 5 to 20 times by weight of an extraction solvent thereto. In addition, it is carried out by dipping at room temperature to 100 ° C., preferably 30 to 50 ° C., for 12 to 150 hours, preferably 24 to 48 hours. In this extraction, it is preferable to shake or mechanically stir.

次いで、この抽出物を、産業用ろ紙、ケイ藻土、遠心分離、メンブレインフィルターなどを用いる固液分離手段で清澄化することにより、本発明で用いる植物抽出物を得ることができる。   Subsequently, this extract is clarified by solid-liquid separation means using industrial filter paper, diatomaceous earth, centrifugal separation, membrane filter or the like, whereby the plant extract used in the present invention can be obtained.

この被抽出植物からの抽出物は、必要により公知の精製手段、例えば、適切な各種カラムクロマトグラフィー、限外濾過等を用いて更に精製し、チロシナーゼ活性阻害剤とすることもできる。また、必要に応じて、公知の乾燥手段、例えばスプレードライ、凍結乾燥、ドラム乾燥等により粉末化したチロシナーゼ活性阻害剤とすることもできる。   The extract from the plant to be extracted can be further purified by using a known purification means, for example, appropriate various column chromatography, ultrafiltration, etc. as necessary to obtain a tyrosinase activity inhibitor. Moreover, it can also be set as the tyrosinase activity inhibitor pulverized by the well-known drying means, for example, spray drying, freeze drying, drum drying etc. as needed.

以上のようにして得られる本発明のチロシナーゼ活性阻害剤は、常法に従い、皮膚外用剤や美白化粧料に配合して使用することができる。   The tyrosinase activity inhibitor of the present invention obtained as described above can be used by blending with a skin external preparation or a whitening cosmetic composition according to a conventional method.

例えば、美白化粧料とする場合は、公知の化粧料基剤に、上記チロシナーゼ活性阻害剤を、例えば、0.001ないし5質量%程度配合し、常法に従って、化粧液、乳液、クリーム、ペーストとすればよい。   For example, in the case of whitening cosmetics, for example, about 0.001 to 5% by mass of the above tyrosinase activity inhibitor is blended with a known cosmetic base, and cosmetics, emulsions, creams, pastes are added according to conventional methods. And it is sufficient.

次に参考例および実施例を挙げ、本発明を更に詳しく説明するが、本発明はこれら実施例等に何ら制約されるものではない。   EXAMPLES Next, although a reference example and an Example are given and this invention is demonstrated in more detail, this invention is not restrict | limited at all by these Examples.

参 考 例 1
被抽出植物からの抽出物の取得:
被抽出植物として、を入手し、それらを下記抽出操作に付し、被抽出植物の抽出物を、植物エキスとして得た。
Reference example 1
Obtaining extracts from extracted plants:
As the plant to be extracted, they were obtained and subjected to the following extraction operation to obtain an extract of the plant to be extracted as a plant extract.

( 抽出操作 )
各被抽出植物を部位別に適当な大きさに裁断した後、それぞれを60℃で12時間乾燥させ、これを遠心粉砕器(MRK−Retschm,ZM−100)を用いて粉砕した。0.5mmのスクリーンを通過したものを集め、これについて、高速溶媒抽出装置(日本ダイオネクス社製、ASE−200)を用いて溶媒抽出を行った。即ち、それぞれ乾燥重量で2gの試料を8gのケイソウ土とともに抽出セルに装填し、50%エタノール溶液をにより、抽出温度80℃、抽出時間10分、圧力1500psi、抽出回数2回で、合計50mlの植物エキスを得た。
(Extraction operation)
Each plant to be extracted was cut into an appropriate size for each part and then dried at 60 ° C. for 12 hours, and pulverized using a centrifugal pulverizer (MRK-Retschm, ZM-100). What passed through a 0.5 mm screen was collected, and this was subjected to solvent extraction using a high-speed solvent extraction device (Nippon Dionex, ASE-200). That is, 2 g of each sample in dry weight was loaded into an extraction cell together with 8 g of diatomaceous earth, and a 50% ethanol solution was used to extract 50 ml in total at an extraction temperature of 80 ° C., an extraction time of 10 minutes, a pressure of 1500 psi, and two extractions. A plant extract was obtained.

実 施 例 1
参考例1で得られた植物エキスを、イオン交換水で10倍希釈し(以下、「試料溶液」という)、チロシナーゼ阻害活性試験に供した。まず、チロシナーゼ(マッシュルーム由来、Sigma社製)を、イオン交換水で40U/mlに調整し、酵素溶液とした。また、3,4−ジヒドロキシ−L−フェニルアラニン(以下、「DOPA」という;Sigma社製)を、イオン交換水で2.5mMに調整し、基質溶液とした。更に、1/15Mリン酸バッファー(pH6.8)を緩衝液として用いた。
Example 1
The plant extract obtained in Reference Example 1 was diluted 10 times with ion-exchanged water (hereinafter referred to as “sample solution”) and subjected to a tyrosinase inhibitory activity test. First, tyrosinase (derived from mushrooms, manufactured by Sigma) was adjusted to 40 U / ml with ion-exchanged water to obtain an enzyme solution. In addition, 3,4-dihydroxy-L-phenylalanine (hereinafter referred to as “DOPA”; manufactured by Sigma) was adjusted to 2.5 mM with ion-exchanged water to obtain a substrate solution. Furthermore, 1 / 15M phosphate buffer (pH 6.8) was used as a buffer solution.

酵素反応は、96穴マイクロプレートにて行った。マイクロプレートの各ウェルに緩衝液100μl、酵素溶液40μlおよび試料溶液20μlを加え、充分混合撹拌し、23℃で3分間プレインキュベートした。プレインキュベート後に基質溶液50μlを添加し、直ちに490nmにおける吸光度(As0)を測定した。23℃で10分間酵素反応を行い、反応10分後の吸光度(As10)を測定した。さらに、試料溶液20μlの代わりに5%エタノール溶液20μlを加えた系および酵素溶液40μlの代わりに緩衝液40μlを加えた系において同様に反応させ、それぞれの場合における反応開始直後および10分後の吸光度(Ac0、Ac10及びAb0、Ab10)を測定した。チロシナーゼ阻害活性は以下の式により算出した。   The enzyme reaction was performed in a 96-well microplate. To each well of the microplate, 100 μl of buffer solution, 40 μl of enzyme solution and 20 μl of sample solution were added, mixed well, and pre-incubated at 23 ° C. for 3 minutes. After pre-incubation, 50 μl of the substrate solution was added, and the absorbance at 490 nm (As0) was immediately measured. The enzyme reaction was performed at 23 ° C. for 10 minutes, and the absorbance (As10) after 10 minutes of the reaction was measured. Furthermore, the reaction was carried out in the same manner in a system in which 20 μl of a 5% ethanol solution was added instead of 20 μl of the sample solution and a system in which 40 μl of a buffer solution was added instead of 40 μl of the enzyme solution, and the absorbance immediately after the start of the reaction and after 10 minutes in each case. (Ac0, Ac10 and Ab0, Ab10) were measured. Tyrosinase inhibitory activity was calculated by the following formula.

チロシナーゼ阻害率(%)=100−[[(As10−Ab10)―
(As0−Ab0)]/(Ac10−Ac0)×100]
Tyrosinase inhibition rate (%) = 100 − [[(As10−Ab10) −
(As0−Ab0)] / (Ac10−Ac0) × 100]

各試料溶液におけるチロシナーゼ阻害活性を表1に示す。また、試料溶液を減圧乾固し、5%エタノール溶液に所定濃度で再溶解したものを使用し、その濃度を段階的に減少させて上記チロシナーゼ阻害活性試験を行い、チロシナーゼ阻害活性が50%になる濃度、すなわち試料溶液におけるチロシナーゼの50%阻害濃度(IC50,mg/ml)を内挿法により求めた。その結果を表2に示す。 Table 1 shows the tyrosinase inhibitory activity in each sample solution. In addition, the sample solution was dried under reduced pressure and redissolved in a 5% ethanol solution at a predetermined concentration. The concentration was decreased stepwise, and the tyrosinase inhibitory activity test was conducted. The tyrosinase inhibitory activity was reduced to 50%. The concentration of tyrosinase in the sample solution (IC 50 , mg / ml) was determined by interpolation. The results are shown in Table 2.

Figure 2009227612
Figure 2009227612

Figure 2009227612
Figure 2009227612

表1および表2から明らかなように、本発明の植物抽出物は、優れたチロシナーゼ阻害活性を有していた。   As is clear from Tables 1 and 2, the plant extract of the present invention had excellent tyrosinase inhibitory activity.

実 施 例 2
美 白 化 粧 水(1) :
下記組成、製法により美白化粧水を調製した。このものは優れた美白作用を有していた。
( 組 成 ) (質量%)
(1)グリセリン 5
(2)1,3−ブチレングリコール 5
(3)POE(20)ソルビタンモノラウリン酸エステル 1
(4)エタノール 8
(5)ウスジロイソマツ抽出物*
(6)防腐剤 適 量
(7)香料 適 量
(8)精製水 残 量
*参考例1で得たもの
Example 2
Whitening skin lotion (1):
A whitening lotion was prepared by the following composition and production method. This product had an excellent whitening effect.
(Composition) (mass%)
(1) Glycerin 5
(2) 1,3-butylene glycol 5
(3) POE (20) sorbitan monolaurate 1
(4) Ethanol 8
(5) Usujiro pine extract * 2
(6) Preservative appropriate amount (7) Perfume appropriate amount (8) Remaining amount of purified water
* Obtained in Reference Example 1

( 製 法 )
(イ)(8)に(1)、(2)をこの順に逐次溶解させる
(ロ)(4)に(3)、(5)、(6)、(7)、(9)をこの順に逐次溶解させる
(ハ)(イ)で得た水溶液と、(ロ)で得たエタノール水溶液を真空乳化器を用いて
混合した後、容器に充填して半透明な美白化粧水を得た。
(Production method)
(B) (1) and (2) are sequentially dissolved in this order in (8) (b) (3), (5), (6), (7), and (9) are sequentially added in this order in (4) Dissolve (c) The aqueous solution obtained in (a) and the aqueous ethanol solution obtained in (b) using a vacuum emulsifier.
After mixing, the container was filled to obtain a translucent whitening lotion.

実 施 例 3
美 白 化 粧 水(2):
下記組成、製法により美白化粧水を調製した。このものは優れた美白作用を有していた。
( 組 成 ) (質量%)
(1)1,3−ブチレングリコール 5
(2)PEG1500 8
(3)ソルビトール 7
(4)ヒアルロン酸 0.2
(5)エタノール 7
(6)POE(5)オレイルアルコールエーテル 6
(7)アカギ抽出物**
(8)オリーブオイル 0.2
(9)精製水 残 量
**参考例1で得たもの
Example 3
Whitening skin lotion (2):
A whitening lotion was prepared by the following composition and production method. This product had an excellent whitening effect.
(Composition) (mass%)
(1) 1,3-butylene glycol 5
(2) PEG 1500 8
(3) Sorbitol 7
(4) Hyaluronic acid 0.2
(5) Ethanol 7
(6) POE (5) oleyl alcohol ether 6
(7) Akagi extract ** 1
(8) Olive oil 0.2
(9) Residual amount of purified water
** Obtained in Reference Example 1

( 製 法 )
(イ)(9)に(1)、(2)、(3)、(4)をこの順に逐次溶解させる
(ロ)(5)に(6)、(7)、(8)をこの順に逐次溶解させる
(ハ)(イ)で得た水溶液と、(ロ)で得たエタノール溶液を真空乳化器を用いて
混合した後、容器に充填して半透明な美白化粧水(エッセンス)を得た。
(Production method)
(A) (1), (2), (3), (4) are sequentially dissolved in this order in (9). (B) (6), (7), (8) are sequentially dissolved in this order in (5). Dissolve (c) The aqueous solution obtained in (a) and the ethanol solution obtained in (b) using a vacuum emulsifier.
After mixing, the container was filled to obtain a translucent whitening lotion (essence).

実 施 例 4
美 白 化 粧 水(3):
下記組成、製法により美白化粧水を調製した。このものは優れた美白作用を有していた。
( 組 成 ) (質量%)
(1)ジプロピレングリコール 5
(2)PEG400 5
(3)エタノール 7
(4)リュウキュウツチトリモチ抽出物+
(5)キサンタンガム 0.2
(6)POE(6−20)ソルビタンモノステアリン酸
エステル 1
(7)オレイルアルコール 0.5
(8)アスコルビン酸 2
(9)ビタミンEアセテート 0.2
(10)精製水 残 量
+リュウキュウツチトリモチ地上部の50%エタノール抽出液
Example 4
Whitening skin lotion (3):
A whitening lotion was prepared by the following composition and production method. This product had an excellent whitening effect.
(Composition) (mass%)
(1) Dipropylene glycol 5
(2) PEG400 5
(3) Ethanol 7
(4) Ryukyu Tsuritori extract + 6
(5) Xanthan gum 0.2
(6) POE (6-20) sorbitan monostearic acid
Ester 1
(7) Oleyl alcohol 0.5
(8) Ascorbic acid 2
(9) Vitamin E acetate 0.2
(10) Residual amount of purified water
+ 50% ethanol extract from above ground

( 製 法 )
(イ)(10)に(5)、(1)、(2)、(8)をこの順に逐次溶解させる
(ロ)(3)に(7)、(6)、(4)、(9)をこの順に逐次溶解させる
(ハ)(イ)で得た水溶液と、(ロ)で得たエタノール溶液を真空乳化器を用いて
混合した後、容器に充填して乳白色な美白化粧水(エッセンス)を得た。
(Production method)
(B) (5), (1), (2), (8) are sequentially dissolved in this order in (10) (b) (7), (6), (4), (9) in (3) (C) The aqueous solution obtained in (a) and the ethanol solution obtained in (b) are dissolved using a vacuum emulsifier.
After mixing, the container was filled to obtain a milky whitening lotion (essence).

実 施 例 5
化 粧 用 油 剤:
下記組成、製法により化粧用油剤を調製した。このものは優れた美白作用を有していた。
( 組 成 ) (質量%)
(1)オリーブオイル 49
(2)流動パラフィン 30
(3)スクワラン 20
(4)アカバナヒルギ抽出物++ 0.9
(5)ビタミンEアセテート 0.1
++参考例1のアカバナヒルギの実の抽出物
Example 5
Cosmetic oil:
A cosmetic oil was prepared by the following composition and production method. This product had an excellent whitening effect.
(Composition) (mass%)
(1) Olive oil 49
(2) Liquid paraffin 30
(3) Squalane 20
(4) Akabana hirugi extract ++ 0.9
(5) Vitamin E acetate 0.1
++ Extract of red berries of Reference Example 1

( 製 法 )
(イ)(1)を基剤とし、これに(2)、(3)、(4)、(5)を添加し、撹拌す る
(ロ)(イ)をろ過した後、容器に充填して化粧用油剤とした。
(Production method)
(B) Add (2), (3), (4), (5) to this as a base and stir. (B) Filter (b) and fill into a container. And used as a cosmetic oil.

実 施 例 6
美白クリーム:
下記組成、製法により美白クリームを調製した。このものは優れた美白作用を有していた。
( 組 成 ) (質量%)
(1)グリセリン 15
(2)1,3ブチレングリコール 4
(3)水酸化カリウム 0.2
(4)ステアリン酸 3
(5)流動パラフィン 3
(6)ワセリン 7
(7)ステアリン酸モノグリセリド 3
(8)レモンユーカリ抽出物# 0.5
(9)精製水 残 量
#参考例1のもの
Example 6
Whitening cream:
A whitening cream was prepared by the following composition and production method. This product had an excellent whitening effect.
(Composition) (mass%)
(1) Glycerin 15
(2) 1,3 butylene glycol 4
(3) Potassium hydroxide 0.2
(4) Stearic acid 3
(5) Liquid paraffin 3
(6) Vaseline 7
(7) Stearic acid monoglyceride 3
(8) Lemon Eucalyptus Extract # 0.5
(9) Residual amount of purified water
#Things from Reference Example 1

( 製 法 )
(イ)(9)に(1)、(2)、(3)、(8)をこの順に逐次溶解させる
(ロ)(イ)に(4)、(5)、(6)、(7)を加熱融解後、真空乳化器を用いて
混合し、
更に容器に充填して美白クリームを得た。
(Production method)
(A) (1), (2), (3), (8) are sequentially dissolved in this order in (9) (B) (4), (5), (6), (7) in (A) After heating and melting, mix using a vacuum emulsifier,
Further, the container was filled into a whitening cream.

本発明の被抽出植物からの抽出物は優れたチロシナーゼ阻害活性を有するものであった。   The extract from the plant to be extracted of the present invention has excellent tyrosinase inhibitory activity.

従って、この抽出物を有効成分とするチロシナーゼ活性阻害剤は、皮膚外用剤や美白化粧料の有効成分として有利に使用することができるものである。   Therefore, the tyrosinase activity inhibitor containing this extract as an active ingredient can be advantageously used as an active ingredient of a skin external preparation or a whitening cosmetic.

Claims (22)

アカテツ科植物、フトモモ科植物、アカネ科植物、イソマツ科植物、ヒルギ科植物、カキノキ科植物、クワ科植物、サクラソウ科植物、シクンシ科植物、ショウガ科植物、ツチトリモチ科植物、ツバキ科植物、トウダイグサ科植物、ハマザクロ科植物、ヒガンバナ科植物、ムクロジ科植物、モクマオウ科植物およびユり科植物よりなる群より選ばれた植物の抽出物を有効成分とするチロシナーゼ活性阻害剤。   Acanthaceae plant, Myrtaceae plant, Rubiaceae plant, Rubiaceae plant, Hygienaceae plant, Oysteraceae plant, Mulberry plant, Primrose plant, Cyclicaceae plant, Ginger plant plant, Camellia plant, Camellia plant, Euphorbiaceae An inhibitor of tyrosinase activity comprising, as an active ingredient, an extract of a plant selected from the group consisting of a plant, an asteraceae plant, an Amaryllidaceae plant, a Mucrodiaceae plant, a humiliaceae plant, and a lily family plant. 植物の抽出物が、水と低級アルコールの混液による抽出物である請求項1記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1, wherein the plant extract is an extract of a mixture of water and a lower alcohol. アカテツ科植物が、カニステルまたはサポジラである請求項1または2記載のチロシナーゼ活性阻害剤。   3. The tyrosinase activity inhibitor according to claim 1 or 2, wherein the Acanthaceae plant is canister or sapodilla. フトモモ科植物が、オオフトモモ、レモンユーカリまたはアデクである請求項1または2記載のチロシナーゼ活性阻害剤。   3. The tyrosinase activity inhibitor according to claim 1 or 2, wherein the myrtaceae plant is a white peach, lemon eucalyptus, or adek. アカネ科植物が、ボチョウジまたはベニデマリである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the Rubiaceae plant is Boscoji or Benidemari. イソマツ科植物が、ウスジロイソマツまたはウコンイソマツである請求項1または2記載のチロシナーゼ活性阻害剤。 The tyrosinase activity inhibitor according to claim 1 or 2, wherein the Pinus firaceae plant is Usujiro pine or Turmeric pine. ヒルギ科植物が、アカバナヒルギまたはメヒルギである請求項1または2記載のチロシナーゼ活性阻害剤。 3. The tyrosinase activity inhibitor according to claim 1 or 2, wherein the plant of the family Hygiaceae is red burdock or leeches. カキノキ科植物が、リュウキュウコクタンである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the oyster family is Ryukyu Kokutan. クワ科植物が、パラミツである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the mulberry plant is jackfruit. サクラソウ科植物がハマボッスである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the primaceae plant is a sea cucumber. シクンシ科植物が、ヒルギモドキである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the succulent family plant is a nymph. ショウガ科植物が、ゲットウである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the ginger family plant is ghetto. ツチトリモチ科植物が、リュウキュウツチトリモチである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the plant is a Ryukyu-Tuchimochi. ツバキ科植物が、リュウキュウナガエヒサカキである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the camellia plant is Ryukyu Nagaehisakaki. トウダイグサ科植物が、アカギである請求項1または2記載のチロシナーゼ活性阻害剤。   3. The tyrosinase activity inhibitor according to claim 1 or 2, wherein the Euphorbiaceae plant is redwood. ハマザクロ科植物が、マヤプシキである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the genus Pleurotus is Mayopushiki. ヒガンバナ科植物が、ハマユウである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the Amaryllidaceae plant is Hamayu. ムクロジ科植物が、タイワンモクゲンジである請求項1または2記載のチロシナーゼ活性阻害剤。   3. The tyrosinase activity inhibitor according to claim 1 or 2, wherein the musculodaceae plant is Taiwan mokugenji. モクマオウ科植物が、モクマオウである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the asteraceae plant is a humus. ユリ科植物が、ハマサルトリイバラである請求項1または2記載のチロシナーゼ活性阻害剤。   The tyrosinase activity inhibitor according to claim 1 or 2, wherein the lily family plant is a kingfisher rose. 請求項第1項ないし第20項の何れかの項記載のチロシナーゼ活性阻害剤を含有する皮膚外用剤。   A skin external preparation containing the tyrosinase activity inhibitor according to any one of claims 1 to 20. 請求項第1項ないし第20項の何れかの項記載のチロシナーゼ活性阻害剤を含有する美白化粧料。   A whitening cosmetic comprising the tyrosinase activity inhibitor according to any one of claims 1 to 20.
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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010215566A (en) * 2009-03-17 2010-09-30 Noevir Co Ltd Humectant, anti-aging agent, neutral fat accumulation inhibitor, bleaching agent, anti-inflammatory agent, skin agent for external use and oral agent
JP2011184354A (en) * 2010-03-08 2011-09-22 National Institute Of Advanced Industrial Science & Technology Bleaching agent inhibiting melanin uptake into keratinocyte
CN102764320A (en) * 2012-06-26 2012-11-07 广州中医药大学 Psychotria sp. extract, and preparation method and antineoplastic application thereof
JP2013530224A (en) * 2010-06-30 2013-07-25 エイボン プロダクツ インコーポレーテッド Composition and method for improving the appearance of the skin by stimulating MAGP-1
CN103571680A (en) * 2012-07-24 2014-02-12 黑龙江省轻工科学研究院 Preparation method for lucuma-nervosa fruit wine
CN104382801A (en) * 2014-12-04 2015-03-04 浙江树人大学 Kandelia candel leaf total flavonoid nano-emulsion for whitening skin and removing freckles and gel thereof
JP2017218382A (en) * 2016-06-02 2017-12-14 国立大学法人 琉球大学 Parp inhibitor containing syzygium samarangense extract
JP2018062481A (en) * 2016-10-12 2018-04-19 株式会社バスクリン Arbutin-containing composition, and method for inhibiting the degradation of arbutin
JP2019516777A (en) * 2016-02-24 2019-06-20 花王株式会社 Whitening agent
WO2022136067A1 (en) * 2020-12-23 2022-06-30 Workforce Biologics Ltd Formulation comprising p-menthane-3,8-diol

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105062133B (en) * 2015-09-10 2017-03-01 福建省农业科学院果树研究所 The extracting method of anthocyanidin in a kind of Eugenia javanica Lam peel

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05124952A (en) * 1991-11-05 1993-05-21 Tsuneo Nanba Cosmetic
JPH0616530A (en) * 1992-07-03 1994-01-25 Mikimoto Pharmaceut Co Ltd Cosmetic
JPH06305978A (en) * 1993-04-21 1994-11-01 Maruzen Pharmaceut Co Ltd Tyrosinase inhibitor, beautifying cosmetic and color change preventing agent
JPH0912441A (en) * 1995-06-27 1997-01-14 Mikimoto Pharmaceut Co Ltd Cosmetic
JPH0930947A (en) * 1995-07-21 1997-02-04 Shiseido Co Ltd Beautifying and whitening dermal preparation for external use
JPH0995436A (en) * 1995-07-21 1997-04-08 Shiseido Co Ltd Preparation for external use for skin
JP2003055189A (en) * 2001-08-07 2003-02-26 Koei Kogyo Kk Skin care preparation

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05124952A (en) * 1991-11-05 1993-05-21 Tsuneo Nanba Cosmetic
JPH0616530A (en) * 1992-07-03 1994-01-25 Mikimoto Pharmaceut Co Ltd Cosmetic
JPH06305978A (en) * 1993-04-21 1994-11-01 Maruzen Pharmaceut Co Ltd Tyrosinase inhibitor, beautifying cosmetic and color change preventing agent
JPH0912441A (en) * 1995-06-27 1997-01-14 Mikimoto Pharmaceut Co Ltd Cosmetic
JPH0930947A (en) * 1995-07-21 1997-02-04 Shiseido Co Ltd Beautifying and whitening dermal preparation for external use
JPH0995436A (en) * 1995-07-21 1997-04-08 Shiseido Co Ltd Preparation for external use for skin
JP2003055189A (en) * 2001-08-07 2003-02-26 Koei Kogyo Kk Skin care preparation

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010215566A (en) * 2009-03-17 2010-09-30 Noevir Co Ltd Humectant, anti-aging agent, neutral fat accumulation inhibitor, bleaching agent, anti-inflammatory agent, skin agent for external use and oral agent
JP2011184354A (en) * 2010-03-08 2011-09-22 National Institute Of Advanced Industrial Science & Technology Bleaching agent inhibiting melanin uptake into keratinocyte
JP2013530224A (en) * 2010-06-30 2013-07-25 エイボン プロダクツ インコーポレーテッド Composition and method for improving the appearance of the skin by stimulating MAGP-1
CN102764320A (en) * 2012-06-26 2012-11-07 广州中医药大学 Psychotria sp. extract, and preparation method and antineoplastic application thereof
CN102764320B (en) * 2012-06-26 2014-03-05 广州中医药大学 Psychotria sp. extract, and preparation method and antineoplastic application thereof
CN103571680A (en) * 2012-07-24 2014-02-12 黑龙江省轻工科学研究院 Preparation method for lucuma-nervosa fruit wine
CN104382801A (en) * 2014-12-04 2015-03-04 浙江树人大学 Kandelia candel leaf total flavonoid nano-emulsion for whitening skin and removing freckles and gel thereof
JP2019516777A (en) * 2016-02-24 2019-06-20 花王株式会社 Whitening agent
US11090351B2 (en) 2016-02-24 2021-08-17 Kao Corporation Whitening agent
JP7028803B2 (en) 2016-02-24 2022-03-02 花王株式会社 Whitening agent
JP2017218382A (en) * 2016-06-02 2017-12-14 国立大学法人 琉球大学 Parp inhibitor containing syzygium samarangense extract
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