JP2017128538A - Endo180 production promoter - Google Patents
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Abstract
Description
本発明は、Endo180産生促進剤に関するものである。 The present invention relates to an Endo180 production promoter.
紫外線の長期曝露によって引き起こされる光老化では、真皮コラーゲン線維構造の量的、質的変化が確認され、シワ形成への関与が知られている。コラーゲン線維構造は繰り返し起こるコラーゲン線維の合成と分解の代謝バランスによって恒常性が維持されている。この分解過程には、マトリックスメタロプロテアーゼによるコラーゲンの断片化と、断片化されたコラーゲンの線維芽細胞への取り込み、分解が含まれている。このうちコラーゲン断片の細胞内への取り込みには膜タンパク質であるコラーゲンレセプター「Endo180」の関与が知られている(非特許文献1)。 In photoaging caused by long-term exposure to ultraviolet rays, quantitative and qualitative changes in the dermal collagen fiber structure have been confirmed, and their involvement in wrinkle formation is known. The collagen fiber structure is maintained in homeostasis by the metabolic balance between repetitive collagen fiber synthesis and degradation. This degradation process includes fragmentation of collagen by matrix metalloprotease and incorporation of fragmented collagen into fibroblasts and degradation. Among these, the collagen receptor “Endo180”, which is a membrane protein, is known to be involved in the incorporation of collagen fragments into cells (Non-patent Document 1).
Endo180はマンノース受容体C2(MRC2)、ウロキナーゼプラスミノーゲン活性化因子受容体関連タンパク質(uPARAP)およびCD280としても知られる受容体で、コラーゲンなどの結合したリガンドをエンドソームにおける分解へと誘導する、リサイクルされるエンドサイトーシス受容体である。 Endo180 is a receptor also known as mannose receptor C2 (MRC2), urokinase plasminogen activator receptor associated protein (uPARAP) and CD280, which induces a bound ligand, such as collagen, for degradation in the endosome. Is an endocytic receptor.
Endo180は、マクロファージマンノース受容体ファミリーであるマンノース受容体、ホスホリパーゼA2、およびDEC−205/MR6と相同性を共有する。Endo180は、原形質膜から、後期エンドソーム/リソソーム区画までではなく、リサイクリングエンドソームまでが標的とされるという点で、マンノース受容体のファミリーの中でも特殊であり、細胞遊走、および細胞内分解のためのコラーゲンの取り込みを促進することによって、細胞運動性および細胞外マトリックスの再構築において機能を果たす。 Endo180 shares homology with the mannose receptor, phospholipase A2, and DEC-205 / MR6, a family of macrophage mannose receptors. Endo180 is unique among the family of mannose receptors in that it is targeted to the recycling endosome rather than the plasma membrane to the late endosomal / lysosomal compartment for cell migration and intracellular degradation. It functions in cell motility and extracellular matrix remodeling by promoting the uptake of collagen.
また、uPARAPとして、ウロキナーゼ型プラスミン活性化因子(uPA)およびウロキナーゼ型プラスミン活性化因子受容体(uPAR)と三重複合体を形成し、プラスミノーゲンからのプラスミンの生成に関与する。 In addition, uPARAP forms a ternary complex with urokinase-type plasmin activator (uPA) and urokinase-type plasmin activator receptor (uPAR), and is involved in the production of plasmin from plasminogen.
Endo180は、細胞表面上のクラスリンで覆われたピット、およびエンドソームにおいて局在化する。線維芽細胞、内皮細胞、およびマクロファージにおいて主に発現される。組織としては肺、血管、骨および皮膚において、主に発現される(特許文献1参照)。 Endo180 is localized in clathrin-covered pits and endosomes on the cell surface. It is mainly expressed in fibroblasts, endothelial cells, and macrophages. As a tissue, it is mainly expressed in lung, blood vessel, bone and skin (see Patent Document 1).
一方、皮膚の真皮もコラーゲンに富む組織であるが、真皮中のコラーゲン線維のリモデリングにおけるEndo180の関与に関する報告は少ない。これまでに、光老化皮膚では線維芽細胞のEndo180発現低下と、それに伴う真皮マトリックスへの断片化コラーゲンを蓄積することが知られている(非特許文献2)。また、断片化コラーゲンによって線維芽細胞に酸化ストレスが誘導されることが知られている(非特許文献3)。さらに、紫外線によるEndo180発現低下メカニズムにケラチノサイトが産生するIL−1αが関与していることも知られている(非特許文献4)。このことから紫外線の長期曝露によって引き起こされる光老化皮膚の形成にEndo180の関与が考えられる。そのメカニズムとして線維芽細胞のEndo180発現低下によって断片化コラーゲンの取り込みが抑えられることで、正常なコラーゲン線維構造の再生が障害され、また細胞周囲への断片化コラーゲンの蓄積によって線維芽細胞の機能障害を誘導することが考えられるため、Endo180発現低下はシワの形成に寄与する可能性が考えられる。 On the other hand, although the dermis of the skin is also a tissue rich in collagen, there are few reports regarding the involvement of Endo180 in remodeling of collagen fibers in the dermis. So far, it has been known that, in photoaged skin, the expression of Endo180 in fibroblasts is reduced and fragmented collagen is accumulated in the dermal matrix (Non-Patent Document 2). Further, it is known that oxidative stress is induced in fibroblasts by fragmented collagen (Non-patent Document 3). Furthermore, it is also known that IL-1α produced by keratinocytes is involved in the mechanism of lowering Endo180 expression by ultraviolet light (Non-patent Document 4). This suggests that Endo180 is involved in the formation of photoaged skin caused by long-term exposure to ultraviolet rays. As the mechanism, the reduction of Endo180 expression in fibroblasts suppresses the uptake of fragmented collagen, thereby impairing the regeneration of normal collagen fiber structure, and the impairment of fibroblasts due to the accumulation of fragmented collagen around the cells. Therefore, the decrease in Endo180 expression may contribute to the formation of wrinkles.
従って、皮膚におけるEndo180発現を促進する物質はシワ形成を予防または改善することができると考えられる。 Therefore, it is considered that a substance that promotes Endo180 expression in the skin can prevent or improve wrinkle formation.
そのため、Endo180発現の促進を高めるべく、例えばEndo180発現を促進することにより、光老化皮膚における線維芽細胞のEndo180発現を促進し、正常なコラーゲン線維構造の再生を促し、シワの形成を抑えることが考えられる。Endo180の発現を促進する成分として、カフェイン、トコフェロールや(−)カテキン(特許文献2参照)などが知られている。 Therefore, in order to enhance the promotion of Endo180 expression, for example, by promoting Endo180 expression, it promotes Endo180 expression of fibroblasts in photoaged skin, promotes regeneration of normal collagen fiber structure, and suppresses the formation of wrinkles. Conceivable. As components that promote the expression of Endo180, caffeine, tocopherol, (−) catechin (see Patent Document 2), and the like are known.
本発明は、天然物由来の化合物の中からEndo180産生促進作用を有するものを見出し、それを有効成分とするEndo180産生促進剤を提供することを目的とする。 An object of the present invention is to find an endo180 production promoter from natural products and to provide an endo180 production promoter containing the compound as an active ingredient.
上記課題を解決するために、本発明のEndo180産生促進剤は、ロスマリン酸、カフェ酸及びメリッサ抽出物から選ばれる少なくとも1種以上を配合することを特徴とする。 In order to solve the above problems, the Endo180 production promoter of the present invention is characterized by blending at least one selected from rosmarinic acid, caffeic acid and Melissa extract.
本発明によれば、ロスマリン酸、カフェ酸及びメリッサ抽出物から選ばれる少なくとも1種以上を有効成分として含有させることにより、作用効果に優れたEndo180産生促進剤を提供することができる。 ADVANTAGE OF THE INVENTION According to this invention, the Endo180 production promoter excellent in the effect can be provided by containing as an active ingredient at least 1 or more types chosen from a rosmarinic acid, a caffeic acid, and a Melissa extract.
以下、本発明の実施の形態について説明する。
本実施形態のEndo180産生促進剤は、ロスマリン酸、カフェ酸及びメリッサ抽出物から選ばれる少なくとも1種以上を有効成分として含有するものである。
Embodiments of the present invention will be described below.
The Endo180 production promoter of this embodiment contains at least one selected from rosmarinic acid, caffeic acid and Melissa extract as an active ingredient.
ロスマリン酸は、下記構造式(1)で表わされる化学構造を有し、ロスマリン酸を含有する植物抽出物から単離・精製することにより製造することができる。このようなロスマリン酸を含有する植物抽出物は、植物の抽出に一般に用いられている方法によって得ることができる。ロスマリン酸を含有する植物としては、例えば、メリッサ(Melissa officinalis L.)等が挙げられる。 Rosmarinic acid has a chemical structure represented by the following structural formula (1), and can be produced by isolation and purification from a plant extract containing rosmarinic acid. Such a plant extract containing rosmarinic acid can be obtained by a method generally used for plant extraction. Examples of plants containing rosmarinic acid include Melissa (Melissa officinalis L.).
カフェ酸は、下記構造式(2)で表わされる化学構造を有し、カフェ酸を含有する植物抽出物から単離・精製することにより製造することができる。このようなカフェ酸を含有する植物抽出物は、植物の抽出に一般に用いられている方法によって得ることができる。カフェ酸を含有する植物としては、例えば、メリッサ(Melissa officinalis L.)等が挙げられる。 Caffeic acid has a chemical structure represented by the following structural formula (2), and can be produced by isolation and purification from a plant extract containing caffeic acid. Such a plant extract containing caffeic acid can be obtained by a method generally used for plant extraction. Examples of plants containing caffeic acid include Melissa officinalis L. and the like.
メリッサ(Melissa officinalis L.)は、ヨーロッパ全土、中央アジア、北アメリカ等に分布するシソ科の多年生草本であり、これらの地域から容易に入手することができる。抽出原料として使用し得るメリッサの構成部位としては、例えば、葉部、茎部、花部等の地上部、根部又はこれらの部位の混合物等が挙げられるが、好ましくは葉部及び/又は茎部である。 Melissa (Melissa officinalis L.) is a perennial herb that is distributed throughout Europe, Central Asia, North America, etc., and can be easily obtained from these regions. Examples of the constituent parts of Melissa that can be used as an extraction raw material include above-ground parts such as leaves, stems, and flower parts, root parts, or a mixture of these parts, but preferably leaves and / or stems. It is.
前記、抽出物は、植物の抽出に一般に用いられている方法により容易に得ることができる。なお、前記ロスマリン酸およびカフェ酸もしくはメリッサからの抽出物には、ロスマリン酸およびカフェ酸もしくはメリッサからの抽出物、該抽出液の希釈液を乾燥して得られる乾燥物、又はこれらの粗精製物もしくは精製物のいずれもが含まれる。 The extract can be easily obtained by a method generally used for plant extraction. In addition, the extract from rosmarinic acid and caffeic acid or melissa includes an extract from rosmarinic acid and caffeic acid or melissa, a dried product obtained by drying a diluted solution of the extract, or a roughly purified product thereof. Alternatively, any purified product is included.
前記抽出原料であるメリッサの葉部及び/又は茎部は、乾燥した後、そのまま又は粗砕機を用い粉砕して溶媒抽出に供することにより得ることができる。乾燥は天日で行ってもよいし、通常使用されている乾燥機を用いて行ってもよい。前記メリッサは、ヘキサン、ベンゼン等の非極性溶媒によって脱脂等の前処理を施してから抽出原料として使用してもよい。なお、脱脂等の前処理を行うことにより、メリッサの極性溶媒による抽出処理を効率よく行うことができる。 The leaf part and / or stem part of Melissa, which is the raw material for extraction, can be obtained by drying or pulverizing it as it is or using a crusher and subjecting it to solvent extraction. Drying may be performed in the sun or using a commonly used dryer. The melissa may be used as an extraction raw material after pretreatment such as degreasing with a nonpolar solvent such as hexane or benzene. In addition, by performing pretreatments such as degreasing, extraction with Melissa's polar solvent can be performed efficiently.
前記抽出に用いる溶媒としては、水、親水性有機溶媒、又はこれらの混合溶媒を室温乃至溶媒の沸点以下の温度で用いることが好ましい。 As the solvent used for the extraction, it is preferable to use water, a hydrophilic organic solvent, or a mixed solvent thereof at a temperature from room temperature to the boiling point of the solvent.
前記抽出溶媒として使用し得る水としては、例えば、純水、水道水、井戸水、鉱泉水、鉱水、温泉水、湧水、淡水等の他、これらに各種処理を施したものが含まれる。水に施す処理としては、例えば、精製、加熱、殺菌、濾過、イオン交換、浸透圧の調整、緩衝化等が含まれる。なお、前記抽出溶媒として使用し得る水には、精製水、熱水、イオン交換水、生理食塩水、リン酸緩衝液、リン酸緩衝生理食塩水等も含まれる。 Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as water that has been subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. The water that can be used as the extraction solvent includes purified water, hot water, ion exchange water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.
前記親水性有機溶媒としては、例えば、メタノール、エタノール、プロピルアルコール、イソプロピルアルコール等の炭素数1〜5の低級アルコール;アセトン、メチルエチルケトン等の低級脂肪族ケトン;1,3−ブチレングリコール、プロピレングリコール、グリセリン等の炭素数2〜5の多価アルコールなどが挙げられ、これら親水性有機溶媒と水との混合溶媒などを用いることができる。
なお、前記水と親水性有機溶媒との混合溶媒を使用する場合には、低級アルコールの場合は水10質量部に対して1質量部〜90質量部、低級脂肪族ケトンの場合は水10質量部に対して1質量部〜40質量部添加することが好ましい。多価アルコールの場合は水10質量部に対して1質量部〜90質量部添加することが好ましい。
Examples of the hydrophilic organic solvent include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene glycol, propylene glycol, Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycerin, and a mixed solvent of these hydrophilic organic solvents and water can be used.
In addition, when using the mixed solvent of the said water and a hydrophilic organic solvent, in the case of a lower alcohol, 1 mass part-90 mass parts with respect to 10 mass parts of water, in the case of a lower aliphatic ketone, 10 masses of water. It is preferable to add 1 to 40 parts by mass with respect to parts. In the case of polyhydric alcohol, it is preferable to add 1 part by mass to 90 parts by mass with respect to 10 parts by mass of water.
本発明において、抽出原料であるメリッサから、Endo180産生促進剤を有する物質を抽出するにあたって特殊な抽出方法を採用する必要はなく、室温又は還流加熱下で、任意の抽出装置を用いて抽出することができる。 In the present invention, it is not necessary to adopt a special extraction method for extracting a substance having an Endo180 production promoter from Melissa, which is an extraction raw material, and extraction is performed using an arbitrary extraction device at room temperature or under reflux heating. Can do.
具体的には、抽出溶媒を満たした処理槽内に、抽出原料としてのメリッサの地上部を投入し、更に必要に応じて時々攪拌しながら、30分間〜2時間静置して可溶性成分を溶出した後、濾過して固形物を除去し、得られた抽出液から抽出溶媒を留去し、乾燥することにより抽出物が得られる。抽出溶媒量は通常、抽出原料の5〜15倍量(質量比)である。抽出条件は、抽出溶媒として水を用いた場合には、通常50℃〜95℃にて1〜4時間程度である。また、抽出溶媒として水とエタノールとの混合溶媒を用いた場合には、通常40℃〜80℃にて30分間〜4時間程度である。なお、溶媒で抽出することにより得られる抽出液は、抽出溶媒が安全性の高いものであれば、そのまま本発明のEndo180産生促進剤として用いることができる。 Specifically, the above-ground part of Melissa as an extraction raw material is put into a processing tank filled with the extraction solvent, and further, if necessary, it is allowed to stand for 30 minutes to 2 hours to elute soluble components. Then, the solid is removed by filtration, the extraction solvent is distilled off from the obtained extract, and the extract is obtained by drying. The amount of the extraction solvent is usually 5 to 15 times (mass ratio) of the extraction raw material. The extraction conditions are usually about 1 to 4 hours at 50 to 95 ° C. when water is used as the extraction solvent. Moreover, when the mixed solvent of water and ethanol is used as an extraction solvent, it is normally 30 minutes-about 4 hours at 40 to 80 degreeC. In addition, the extraction liquid obtained by extracting with a solvent can be used as it is as an Endo180 production promoter of the present invention as long as the extraction solvent is highly safe.
得られるメリッサの抽出液は、該抽出液の希釈液若しくは濃縮液、該抽出液の乾燥物、又はこれらの粗精製物若しくは精製物を得るため、常法に従って希釈、濃縮、乾燥、精製等の処理を施してもよい。 The resulting Melissa extract is diluted, concentrated, dried, purified, etc. according to conventional methods to obtain a diluted or concentrated solution of the extract, a dried product of the extract, or a crudely purified product or purified product thereof. Processing may be performed.
なお、得られるメリッサの抽出液は、Endo180産生促進剤として使用することができるが、濃縮液又はその乾燥物としたものの方が利用しやすい。抽出液の乾燥物を得るにあたっては、吸湿性を改善するためにデキストリン、シクロデキストリン等のキャリアーを添加してもよい。また、前記メリッサの抽出物は、特有の匂いを有しているため、その生理活性の低下を招かない範囲で脱色、脱臭等を目的とする精製を行うことも可能であるが、美容用飲食品に添加する場合には大量に使用するものではないから、未精製のままでも実用上支障はない。なお、精製としては、例えば、活性炭処理、吸着樹脂処理、イオン交換樹脂処理等によって行うことができる。 The obtained Melissa extract can be used as an Endo180 production promoter, but a concentrated solution or a dried product thereof is easier to use. In obtaining a dried extract, a carrier such as dextrin or cyclodextrin may be added to improve hygroscopicity. In addition, since the Melissa extract has a unique odor, it can be purified for the purpose of decolorization, deodorization, etc. within a range that does not cause a decrease in its physiological activity. When added to the product, it is not used in large quantities, so there is no practical problem even if it is not purified. The purification can be performed, for example, by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like.
以上のようにして得られた抽出液、当該抽出液の濃縮物又は当該抽出液の乾燥物からロスマリン酸及びカフェ酸を単離・精製する方法は、特に限定されるものではなく、常法により行うことができる。 The method for isolating and purifying rosmarinic acid and caffeic acid from the extract obtained as described above, the concentrate of the extract or the dried product of the extract is not particularly limited, and is a conventional method. It can be carried out.
以上のようにして得られるロスマリン酸、カフェ酸及びメリッサの抽出物は、Endo180産生促進作用を有しており、これらの作用に基づいて、本発明のEndo180産生促進剤として使用することができる。 The extracts of rosmarinic acid, caffeic acid and Melissa obtained as described above have an Endo180 production promoting action, and can be used as the Endo180 production promoting agent of the present invention based on these actions.
なお、本実施形態においては、ロスマリン酸、カフェ酸及びメリッサ抽出物から選ばれる少なくとも1種以上を上記有効成分として用いてもよいし、これらを混合して上記有効成分として用いてもよい。ロスマリン酸、カフェ酸及びメリッサ抽出物から選ばれる少なくとも1種以上を混合して上記有効成分として用いる場合、その配合比は、ロスマリン酸、カフェ酸及びメリッサ抽出物から選ばれる少なくとも1種以上が有するEndo180産生促進作用の程度等により適宜調整すればよい。 In the present embodiment, at least one selected from rosmarinic acid, caffeic acid and Melissa extract may be used as the active ingredient, or these may be mixed and used as the active ingredient. When at least one selected from rosmarinic acid, caffeic acid and Melissa extract is used as the active ingredient, the blending ratio thereof is at least one selected from rosmarinic acid, caffeic acid and Melissa extract. What is necessary is just to adjust suitably according to the grade etc. of Endo180 production promotion effect.
本実施形態のEndo180産生促進作用剤は、ロスマリン酸、カフェ酸、メリッサ抽出物又はこれらの混合物のみからなるものでもよいし、ロスマリン酸、カフェ酸、メリッサ抽出物又はこれらの混合物を製剤化したものでもよい。 The Endo180 production promoting agent of the present embodiment may consist of rosmarinic acid, caffeic acid, Melissa extract or a mixture thereof, or a formulation of rosmarinic acid, caffeic acid, Melissa extract or a mixture thereof. But you can.
本実施形態のEndo180産生促進作用剤は、デキストリン、シクロデキストリン等の薬学的に許容し得るキャリアーその他任意の助剤を用いて、常法に従い、粉末状、顆粒状、錠剤状、液状等の任意の剤形に製剤化することができる。この際、助剤としては、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、安定剤、矯味・矯臭剤等を用いることができる。Endo180産生促進作用剤は、他の組成物(例えば、皮膚外用剤、美容用飲食品等)に配合して使用することができるほか、軟膏剤、外用液剤、貼付剤等として使用することができる。 The Endo180 production promoting agent of the present embodiment is an arbitrary powdery, granular, tablet, liquid, etc., using a pharmaceutically acceptable carrier such as dextrin and cyclodextrin and other optional auxiliaries according to a conventional method. It can be formulated into a dosage form. In this case, as an auxiliary agent, for example, an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring / flavoring agent, and the like can be used. The Endo180 production promoting agent can be used by blending with other compositions (for example, external preparations for skin, cosmetic foods and drinks, etc.), and can also be used as an ointment, a liquid for external use, a patch, and the like. .
本実施形態のEndo180産生促進作用剤を製剤化した場合、ロスマリン酸、カフェ酸、メリッサ抽出物又はこれらの混合物の含有量は、特に限定されるものではなく、目的に応じて適宜設定することができる。 When the Endo180 production promoting agent of this embodiment is formulated, the content of rosmarinic acid, caffeic acid, Melissa extract or a mixture thereof is not particularly limited, and may be appropriately set according to the purpose. it can.
なお、本実施形態のEndo180産生促進作用剤は、必要に応じて、Endo180産生促進作用を有する他の天然抽出物等を、ロスマリン酸、カフェ酸、メリッサ抽出物又はこれらの混合物とともに配合して有効成分として用いることができる。 In addition, the Endo180 production promoting agent of the present embodiment is effective by blending other natural extracts having an Endo180 production promoting action together with rosmarinic acid, caffeic acid, Melissa extract, or a mixture thereof, if necessary. It can be used as a component.
本実施形態のEndo180産生促進作用剤のヒトに対する投与方法としては、経皮投与、経口投与等が挙げられるが、疾患の種類に応じて、その予防・治療等に好適な方法を適宜選択すればよい。 Examples of the method for administering the Endo180 production-promoting agent of this embodiment to humans include transdermal administration, oral administration, and the like. Depending on the type of disease, a suitable method for its prevention / treatment may be selected as appropriate. Good.
また、本実施形態のEndo180産生促進作用剤の投与量も、疾患の種類、重症度、患者の個人差、投与方法、投与期間等によって適宜増減すればよい。 In addition, the dose of the Endo180 production promoting agent of this embodiment may be appropriately increased or decreased depending on the disease type, severity, individual differences among patients, administration method, administration period, and the like.
また、本実施形態のEndo180産生促進作用剤は、優れたEndo180産生促進作用を有するため、例えば、皮膚外用剤又は飲食品に配合するのに好適である。この場合に、ロスマリン酸、カフェ酸、メリッサ抽出物又はこれらの混合物をそのまま配合してもよいし、ロスマリン酸、カフェ酸、メリッサ抽出物又はこれらの混合物から製剤化したEndo180産生促進作用剤を配合してもよい。 Moreover, since the Endo180 production promotion agent of this embodiment has the outstanding Endo180 production promotion effect | action, it is suitable for mix | blending with a skin external preparation or food-drinks, for example. In this case, rosmarinic acid, caffeic acid, Melissa extract or a mixture thereof may be blended as they are, or an Endo180 production promoting agent formulated from rosmarinic acid, caffeic acid, Melissa extract or a mixture thereof is blended. May be.
ここで、皮膚外用剤としては、その区分に制限はなく、経皮的に使用される皮膚化粧料、医薬部外品、医薬品等を幅広く含むものであり、具体的には、例えば、軟膏、クリーム、乳液、美容液、ローション、パック、ファンデーション、リップクリーム、入浴剤、ヘアートニック、ヘアーローション、石鹸、ボディシャンプー等が挙げられる。 Here, the topical skin preparation is not limited in its category, and includes a wide range of skin cosmetics, quasi-drugs, pharmaceuticals, and the like used transdermally. Creams, milky lotions, beauty essences, lotions, packs, foundations, lip balms, bath salts, hair nicks, hair lotions, soaps, body shampoos and the like.
飲食品としては、その区分に制限はなく、経口的に摂取される一般食品、健康食品、保健機能食品等を幅広く含むものである。 There is no restriction on the category of food and drink, and it includes a wide range of foods such as general foods, health foods, and functional health foods that are taken orally.
なお、本実施形態のEndo180産生促進作用剤は、ヒトに対して好適に適用されるものであるが、それぞれの作用効果が奏される限り、ヒト以外の動物(例えば,マウス,ラット,ハムスター,イヌ,ネコ,ウシ,ブタ,サル等)に対して適用することもできる。 The Endo180 production promoting agent of the present embodiment is suitably applied to humans, but as long as each effect is exhibited, animals other than humans (for example, mice, rats, hamsters, It can also be applied to dogs, cats, cows, pigs, monkeys, etc.).
以下、試験例を示し、本発明を具体的に説明するが、本発明は下記の各例に何ら制限されるものではない。なお、下記試験例においては、被験試料として、表1に示す製品(試料No.1〜3)を使用した。 Hereinafter, although a test example is shown and this invention is demonstrated concretely, this invention is not restrict | limited to each following example at all. In the following test examples, products (sample Nos. 1 to 3) shown in Table 1 were used as test samples.
〔表1〕
試料No. 製品名 製造者名/販売者名
1 ロスマリン酸 和光純薬工業株式会社
2 カフェ酸 和光純薬工業株式会社
3 メリッサ抽出液BG−J凍結乾燥品 丸善製薬株式会社
[Table 1]
Sample No. Product name Manufacturer name / Seller name
1 Rosmarinic Acid Wako Pure Chemical Industries, Ltd. 2 Caffeic Acid Wako Pure Chemical Industries, Ltd. 3 Melissa Extract BG-J Lyophilized Product Maruzen Pharmaceutical Co., Ltd.
〔試験例1〕
−皮膚線維芽細胞におけるEndo180産生促進作用試験−
ヒト正常皮膚線維芽細胞 (NB1RGB)を10% FBS含有ダルベッコMEMを用いて培養した後、トリプシン処理により細胞を回収した。回収した細胞を1.0×105 cells/mLの濃度に0.25% FBS含有ダルベッコMEMで希釈した後、6wellマイクロプレートに1well当たり2mLずつ播種し、一晩培養した。培養終了後、培地を抜き、0.25% FBS含有ダルベッコMEMに溶解した被験試料を各wellに2mL添加し、24時間培養した。培養終了後、常法により総タンパクの調製を行った。
[Test Example 1]
-Endo180 production promoting action test in skin fibroblasts-
Human normal skin fibroblasts (NB1RGB) were cultured using Dulbecco MEM containing 10% FBS, and then cells were collected by trypsin treatment. The collected cells were diluted with Dulbecco MEM containing 0.25% FBS to a concentration of 1.0 × 10 5 cells / mL, then seeded at 2 mL per well on a 6-well microplate, and cultured overnight. After completion of the culture, the medium was removed, and 2 mL of a test sample dissolved in Dulbecco's MEM containing 0.25% FBS was added to each well and cultured for 24 hours. After completion of the culture, total protein was prepared by a conventional method.
調製した試料についてSDS−PAGEを行った後、抗Endo180抗体および抗GAPDH抗体を用いてウエスタンブロッティングを行った。Endo180のタンパク質産生量は、被験試料添加および無添加で培養した細胞のそれぞれから調製したタンパク中のEndo180由来のバンドのNet intensity(バンド強度)を、GAPDH由来のバンドのNet intensityで割ることで、細胞あたりの補正値を算出した。Endo180産生促進率の計算方法は以下のとおりである。 SDS-PAGE was performed on the prepared sample, and then Western blotting was performed using an anti-Endo180 antibody and an anti-GAPDH antibody. The protein production amount of Endo180 is obtained by dividing the net intensity (band intensity) of the band derived from Endo180 in the protein prepared from each of the cells cultured with and without the addition of the test sample by the net intensity of the band derived from GAPDH, A correction value per cell was calculated. The calculation method of Endo180 production promotion rate is as follows.
Endo180産生促進率(%)= A/B×100
A :被験試料添加時の細胞あたりのEndo180産生量
B :被験試料無添加時の細胞あたりのEndo180産生量
Endo180 production promotion rate (%) = A / B × 100
A: Endo180 production amount per cell at the time of test sample addition
B: Endo180 production amount per cell when no test sample is added
〔表2〕ENDO180産生促進率(%)
試料濃度(μg/mL)
1 10
試料No.1 119.4% 114.3%
試料No.2 129.9% 174.6%
試料濃度(μg/mL)
5 50
試料No.3 105.4% 127.0%
[Table 2] Endo180 production promotion rate (%)
Sample concentration (μg / mL)
1 10
Sample No. 1 119.4% 114.3%
Sample No. 2 129.9% 174.6%
Sample concentration (μg / mL)
5 50
Sample No. 3 105.4% 127.0%
本発明のロスマリン酸、カフェ酸及びメリッサ抽出物から選ばれる少なくとも1種以上を有効成分として含有するEndo180産生促進剤は、シワ形成の予防または改善に大きく貢献できる。 The Endo180 production promoter containing at least one selected from rosmarinic acid, caffeic acid and Melissa extract of the present invention as an active ingredient can greatly contribute to the prevention or improvement of wrinkle formation.
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