JP2019048786A - Novel collagen reuse promoting effect agent - Google Patents
Novel collagen reuse promoting effect agent Download PDFInfo
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- JP2019048786A JP2019048786A JP2017174324A JP2017174324A JP2019048786A JP 2019048786 A JP2019048786 A JP 2019048786A JP 2017174324 A JP2017174324 A JP 2017174324A JP 2017174324 A JP2017174324 A JP 2017174324A JP 2019048786 A JP2019048786 A JP 2019048786A
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- arthritis
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Abstract
Description
本発明は、断片化コラーゲン代謝促進剤に関するものであり、特にＥｎｄｏ１８０活性化成分を有効成分とする断片化コラーゲン代謝促進剤に関するものである。さらに本発明は、断片化コラーゲン代謝促進剤を含有するシワ改善用組成物および関節炎予防・改善用組成物にも関する。 The present invention relates to a fragmented collagen metabolism promoter, and more particularly to a fragmented collagen metabolism promoter comprising an Endo 180 activating component as an active ingredient. Furthermore, the present invention also relates to a composition for improving wrinkles and a composition for preventing and improving arthritis, which comprises a fragmented collagen metabolism 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ており、シワの形成に関与していると考えられている。コラーゲン線維構造は、コラーゲン線維の合成および分解の繰り返しによる代謝バランスによって恒常性が維持されている。このうち分解過程においては、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および分解とが起こっており、断片化コラーゲン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 light, quantitative and qualitative changes in dermal collagen fiber structure have been confirmed, and are considered to be involved in the formation of wrinkles. The collagen fiber structure is maintained in homeostasis by metabolic balance due to repeated synthesis and degradation of collagen fibers. Among them, in the degradation process, fragmentation of collagen by matrix metalloproteinase and uptake and degradation of fragmented collagen into fibroblasts occur, and for incorporation of fragmented collagen into cells, a membrane is required. Involvement of the protein collagen receptor "Endo 180" is known (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、再利用されるエンドサイトーシス受容体であり、コラーゲンなどのリガンドと結合してこれを細胞内に取り込み、エンドソームにおける分解へと誘導する。 Endo180, also known as mannose receptor C2 (MRC2), urokinase plasminogen activator receptor related protein (uPARAP) and CD280, is an endocytic receptor that is recycled and binds ligands such as collagen It is then taken up into cells and leads to degradation in endosomes.
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、ＤＥＣ−２０５／ＭＲ６などと相同性を有する。Ｅｎｄｏ１８０は、細胞膜から、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、細胞運動性や細胞外マトリックスの再構築において機能を果たす。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。Ｅｎｄｏ１８０は、細胞表面上のクラスリンで覆われたピットや、エンドソーム等に局在しており、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する。組織としては、肺、血管、骨および皮膚において主に発現している（特許文献１参照）。 Endo 180 has homology to the macrophage mannose receptor family, such as mannose receptor, phospholipase A2, DEC-205 / MR6 and the like. Endo180 is unique among the family of mannose receptors in that it is targeted from the cell membrane to the late endosomal / lysosomal compartments, but not to the recycling endosomes, and collagen for cell migration and intracellular degradation Function in cell motility and extracellular matrix remodeling by promoting the uptake of In addition, uPARAP forms a triple complex with urokinase-type plasmin activating factor (uPA) and urokinase-type plasmin activating factor receptor (uPAR), and is involved in the formation of plasmin from plasminogen. Endo 180 is localized to clathrin-coated pits on the cell surface, endosomes, etc., and is mainly expressed in fibroblasts, endothelial cells, and macrophages. Tissues are mainly expressed in lung, blood vessels, bones 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においてＥｎｄｏ１８０発現が低下し、それに伴い真皮マトリックスにおいて断片化コラーゲンが蓄積され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）。これらのことから、Ｅｎｄｏ１８０は、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（例えば、シワの形成）に関与しているものと考えられている。そのメカニズムとしては、線維芽細胞においてＥｎｄｏ１８０の発現が低下すると、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阻害され、また細胞の周辺に断片化コラーゲンが蓄積することにより線維芽細胞の機能障害を誘導するものと考えられる。 On the other hand, the dermis of the skin is also a tissue rich in collagen, but there are few reports on the involvement of Endo180 in remodeling of collagen fibers in the dermis. Heretofore, it has been known that, in photoaging skin, the expression of Endo180 is decreased in fibroblasts, and along with this, fragmented collagen is accumulated in the dermal matrix (Non-patent Document 2). In addition, 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 reducing Endo180 expression by ultraviolet light (Non-patent Document 4). From these, Endo 180 is believed to be involved in the formation of photoaged skin (eg, the formation of wrinkles) caused by prolonged exposure to ultraviolet light. As the mechanism, when the expression of Endo180 is decreased in fibroblasts, the uptake of fragmented collagen is suppressed, the regeneration of normal collagen fiber structure is inhibited, and the fragmented collagen is accumulated around the cells. It is thought to induce fibroblast dysfunction.
そのため、例えば、線維芽細胞においてＥｎｄｏ１８０発現を促進することができれば、断片化したコラーゲンの代謝による再利用や正常なコラーゲン線維構造の再生を促し、光老化皮膚やこれによるシワ等の形成を抑えることができると考えられる。 Therefore, for example, if Endo180 expression can be promoted in fibroblasts, it promotes the reuse of fragmented collagen by metabolism and the regeneration of normal collagen fiber structure, and suppresses the formation of photoaging skin and wrinkles etc. It is believed that
本発明は、優れた断片化コラーゲン代謝促進作用を有する成分を見出し、それを有効成分とする断片化コラーゲン代謝促進剤、ならびに当該断片化コラーゲン代謝促進剤を含有するシワ改善用組成物および関節炎予防・改善用組成物を提供することを目的とする。 The present invention finds a component having an excellent fragmented collagen metabolism promoting action and uses it as an active ingredient, a fragmented collagen metabolism promoting agent, a composition for improving wrinkles containing the fragmented collagen metabolism promoting agent, and arthritis prevention -It aims at providing the composition for improvement.
上記課題を解決するために、本発明者らは、以下の発明を提供する。
〔１〕Ｅｎｄｏ１８０活性化成分を有効成分とすることを特徴とする断片化コラーゲン代謝促進剤。
〔２〕前記Ｅｎｄｏ１８０活性化成分が植物由来成分であることを特徴とする〔１〕に記載の断片化コラーゲン代謝促進剤。
〔３〕前記植物由来成分が、ステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣからなる群より選ばれる１種または２種以上であることを特徴とする〔１〕〔２〕に記載の断片化コラーゲン代謝促進剤。
〔４〕〔１〕〜〔３〕に記載の断片化コラーゲン代謝促進剤を含有することを特徴とするシワ改善用組成物。
〔５〕コラーゲン産生促進剤、血流促進剤、コラーゲン、タンパク質、ペプチドおよびアミノ酸からなる群より選ばれる１種または２種以上の成分を含有することを特徴とする〔４〕に記載のシワ改善用組成物。
〔６〕〔４〕〔５〕に記載のシワ改善用組成物を含有することを特徴とするシワ改善用飲食品。
〔７〕〔１〕〜〔３〕に記載の断片化コラーゲン代謝促進剤を含有することを特徴とする関節炎予防・改善用組成物。
〔８〕コラーゲン産生促進剤、抗炎症剤、血流促進剤、コラーゲン、タンパク質、ペプチド、アミノ酸、ブラックジンジャー、グルコサミン、Ｎ−アセチルグルコサミン、コンドロイチンから選ばれる１種または２種以上の成分を含有することを特徴とする〔７〕に記載の関節炎予防・改善用組成物。
〔９〕〔７〕〔８〕に記載の関節炎予防・改善用組成物を含有することを特徴とする関節炎予防・改善用飲食品。
In order to solve the above-mentioned subject, the present inventors provide the following inventions.
[1] A fragmented collagen metabolism promoter, which comprises an Endo 180 activating component as an active ingredient.
[2] The fragmented collagen metabolism promoter according to [1], wherein the Endo 180 activating component is a plant-derived component.
[3] The plant-derived component is one or more selected from the group consisting of stevia extract, rubusoside, stevioside, rebaudioside A, and rebaudioside C [1] The fragmented collagen metabolism promoter according to [2].
[4] A composition for improving wrinkles, comprising the fragmented collagen metabolism promoter according to [1] to [3].
[5] The wrinkle improvement as described in [4], comprising one or more components selected from the group consisting of collagen production promoters, blood flow promoters, collagen, proteins, peptides and amino acids Composition.
[6] [4] A food or beverage for improving wrinkles comprising the composition for improving wrinkles according to [5].
[7] A composition for preventing and / or improving arthritis, comprising the fragmented collagen metabolism promoter according to [1] to [3].
[8] The composition contains one or more components selected from collagen production promoters, anti-inflammatory agents, blood flow promoters, collagen, proteins, peptides, amino acids, black ginger, glucosamine, N-acetylglucosamine, chondroitin The composition for preventing and improving arthritis according to [7], which is characterized in that
[9] [7] [8] A food or beverage for the prevention and improvement of arthritis, which comprises the composition for the prevention and improvement of arthritis.
本発明によれば、作用効果に優れた断片化コラーゲン代謝促進剤を提供することができる。さらに、当該断片化コラーゲン代謝促進剤を含有させることにより、断片化コラーゲン代謝促進作用に優れたシワ改善用組成物および関節炎予防・改善用組成物を提供することができる。 ADVANTAGE OF THE INVENTION According to this invention, the fragmentation collagen metabolism promoter excellent in the effect can be provided. Furthermore, by including the fragmented collagen metabolism promoter, it is possible to provide a composition for improving wrinkles and a composition for preventing / improving arthritis, which are excellent in fragmented collagen metabolism promoting action.
以下、本発明の実施の形態について説明する。
本実施形態の断片化コラーゲン代謝促進剤は、Ｅｎｄｏ１８０活性化成分を有効成分とするものである。また、本実施形態のシワ改善用組成物および関節炎予防・改善用組成物は、上記断片化コラーゲン代謝促進剤を含有するものである。
Hereinafter, embodiments of the present invention will be described.
The fragmented collagen metabolism promoter of the present embodiment contains the Endo 180 activating component as an active ingredient. The composition for improving wrinkles and the composition for preventing and improving arthritis of the present embodiment contain the above-mentioned fragmented collagen metabolism promoter.
本実施形態において、Ｅｎｄｏ１８０活性化成分は植物由来成分であることが好ましい。かかる植物由来成分としては、Ｅｎｄｏ１８０活性化作用を有するものであれば特に制限されないが、ステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣからなる群より選ばれる１種または２種以上であることが好ましい。 In the present embodiment, the Endo 180 activating component is preferably a plant-derived component. Such plant-derived components are not particularly limited as long as they have Endo 180 activation activity, and one or more selected from the group consisting of stevia extract, rubusoside, stevioside, rebaudioside A and rebaudioside C It is preferable that it is 2 or more types.
〔ステビア抽出物〕
本実施形態において、「ステビア抽出物」には、ステビアを抽出原料として得られる抽出液、当該抽出液の希釈液若しくは濃縮液、当該抽出液を乾燥して得られる乾燥物、又はこれらの粗精製物若しくは精製物のいずれもが含まれる。
[Stevia extract]
In the present embodiment, “the stevia extract” includes an extract obtained by using stevia as an extraction raw material, a diluted solution or concentrate of the extract, a dried product obtained by drying the extract, or crude purification of these The substance or the purified product is included.
ステビア（学名：Stevia rebaudiana）は、アメリカ大陸の熱帯から温帯地方に分布しているキク科ステビア属に属する多年生草本であり、これらの地域から容易に入手することができる。従来、ステビア抽出物は、甘味料等として用いられている。抽出原料として使用し得るステビアの構成部位としては、例えば、葉部、枝部、茎部、花部、蕾部、種子部、地上部、全草、又はこれらの混合物等が挙げられるが、好ましくは葉部である。 Stevia (scientific name: Stevia rebaudiana) is a perennial herb belonging to the genus Stevia, which is distributed in the tropical to temperate regions of the American continent, and can be easily obtained from these regions. Conventionally, stevia extract is used as a sweetener and the like. Examples of the component of stevia that can be used as an extraction raw material include, for example, leaves, branches, stems, flowers, hips, seeds, above-ground parts, whole grass, or a mixture thereof, etc. Is a leaf.
上記植物からの抽出物は、抽出原料を乾燥した後、そのまま又は粗砕機を用いて粉砕し、抽出溶媒による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、通常使用される乾燥機を用いて行ってもよい。また、ヘキサ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。脱脂等の前処理を行うことにより、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 extract from the plant can be obtained by drying the extraction raw material and then grinding it as it is or using a granulator and subjecting it to extraction with an extraction solvent. Drying may be performed in the sun or may be performed using a commonly used dryer. In addition, it may be used as an extraction raw material after being subjected to pretreatment such as degreasing with a nonpolar solvent such as hexane. By performing pretreatment such as degreasing, extraction treatment with a polar solvent can be efficiently performed.
抽出溶媒としては、極性溶媒を使用することが好ましく、例えば、水、親水性有機溶媒等が挙げられ、これらを単独で又は２種以上を組み合わせて、室温又は溶媒の沸点以下の温度で使用することが好ましい。 As an extraction solvent, it is preferable to use a polar solvent, for example, water, a hydrophilic organic solvent, etc., and these are used alone or in combination of two or more thereof at room temperature or at a temperature below the boiling point of the solvent. Is preferred.
抽出溶媒として使用し得る水としては、純水、水道水、井戸水、鉱泉水、鉱水、温泉水、湧水、淡水等のほか、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、浸透圧調整、緩衝化等が含まれる。したがって、本実施形態において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 an extraction solvent include pure water, tap water, well water, spring water, mineral water, hot spring water, spring water, fresh water and the like, as well as those subjected to various treatments. Examples of treatments applied to water include purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering and the like. Therefore, water that can be used as an extraction solvent in the present embodiment also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline and the like.
抽出溶媒として使用し得る親水性有機溶媒としては、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の低級脂肪族アルコール；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の多価アルコール等が挙げられる。 Examples of hydrophilic organic solvents that can be used as extraction solvents include lower aliphatic 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 Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycol, propylene glycol and glycerin.
２種以上の極性溶媒の混合液を抽出溶媒として使用する場合、その混合比は適宜調整することができる。例えば、水と低級脂肪族アルコールとの混合液を抽出溶媒として使用する場合には、水と低級脂肪族アルコールとの混合比が９：１〜１：９（容量比）であることが好ましく、７：３〜２：８（容量比）であることがさらに好ましい。また、水と低級脂肪族ケトンとの混合液を使用する場合には、水と低級脂肪族ケトンとの混合比が９：１〜２：８（容量比）であることが好ましく、水と多価アルコールとの混合液を使用する場合には、水と多価アルコールとの混合比が５：５〜１：９（容量比）であることが好ましい。 When a mixture of two or more polar solvents is used as the extraction solvent, the mixing ratio can be appropriately adjusted. For example, when a mixture of water and a lower aliphatic alcohol is used as the extraction solvent, the mixing ratio of water to the lower aliphatic alcohol is preferably 9: 1 to 1: 9 (volume ratio), More preferably, it is 7: 3 to 2: 8 (volume ratio). When a mixture of water and lower aliphatic ketone is used, the mixing ratio of water to lower aliphatic ketone is preferably 9: 1 to 2: 8 (volume ratio), and more When using a liquid mixture with a polyhydric alcohol, the mixing ratio of water to polyhydric alcohol is preferably 5: 5 to 1: 9 (volume ratio).
抽出処理は、抽出原料に含まれる可溶性成分を抽出溶媒に溶出させ得る限り特に限定はされず、常法に従って行うことができる。例えば、抽出原料の５〜１５倍量（質量比）の抽出溶媒に、抽出原料を浸漬し、常温又は還流加熱下で可溶性成分を抽出させた後、濾過して抽出残渣を除去することにより抽出液を得ることができる。得られた抽出液から溶媒を留去するとペースト状の濃縮物が得られ、この濃縮物をさらに乾燥すると乾燥物が得られる。 The extraction process is not particularly limited as long as soluble components contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent of 5 to 15 times the amount (mass ratio) of the extraction raw material, and after extracting soluble components under normal temperature or reflux heating, filtration is performed to remove the extraction residue A liquid can be obtained. The solvent is distilled off from the obtained extract to obtain a paste-like concentrate, and the concentrate is further dried to obtain a dried product.
なお、上述のようにして得られたステビア抽出液は、そのままでもＥｎｄｏ１８０活性化成分として使用することができるが、濃縮液又は乾燥物としたものの方が使用しやすい。 In addition, although the Stevia extract obtained as mentioned above can be used as an Endo 180 activation component even as it is, a concentrate or a dried product is easier to use.
〔ルブソサイド，ステビオサイド，レバウディオサイドＡ，レバウディオサイドＣ〕
ルブソサイド（１３β−（β−Ｄ−グルコピラノシルオキシ）カウラ−１６−エン−１８−酸β−Ｄ−グルコピラノシル）、ステビオサイド（１３−［（２−Ｏ−β−Ｄ−グルコピラノシル−β−Ｄ−グルコピラノシル）オキシ］カウラ−１６−エン−１８−酸β−Ｄ−グルコピラノシル）、レバウディオサイドＡ（１３−［（２−Ｏ−β−Ｄ−グルコピラノシル−３−Ｏ−β−Ｄ−グルコピラノシル−β−Ｄ−グルコピラノシル）オキシ］カウラ−１６−エン−１８−酸β−Ｄ−グルコピラノシル）、およびレバウディオサイドＣ（１３−［［２−Ｏ−（６−デオキシ−α−Ｌ−マンノピラノシル）−３−Ｏ−（β−Ｄ−グルコピラノシル）−β−Ｄ−グルコピラノシル］オキシ］カウラ−１６−エン−１８−酸β−Ｄ−グルコピラノシル）は、いずれも植物抽出物から得ることのできるステビオール配糖体である。
[Rubusoside, stevioside, rebaudioside A, rebaudioside C]
Rubusoside (13β- (β-D-glucopyranosyloxy) cowla-16-ene-18-acid β-D-glucopyranosyl), stevioside (13-[(2-O-β-D-glucopyranosyl-β-D) -Glucopyranosyl) oxy] cowla-16-ene-18-acid β-D-glucopyranosyl), rebaudioside A (13-[(2-O-β-D-glucopyranosyl-3-O-β-D-glucopyranosyl) -Β-D-glucopyranosyl) oxy] kaura-16-ene-18-acid β-D-glucopyranosyl), and rebaudioside C (13-[[2-O- (6-deoxy-α-L-mannopyranosyl) ) 3-O- (β-D-glucopyranosyl) -β-D-glucopyranosyl] oxy] cowla-16-en-18-acid β-D-glucopyranosyl) is It is a steviol glycoside that can also be obtained from plant extracts.
ルブソサイドを含有する植物抽出物、ならびにステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣのうちの少なくとも１種を含有する植物抽出物は、植物の抽出に一般に用いられる方法によって得ることができる。ルブソサイドを含有する植物としては、甜茶（学名：Rubus suavissimus）が挙げられ、ステビオサイド、レバウディオサイドＡまたはレバウディオサイドＣを含有する植物としては、前述したステビア（学名：Stevia rebaudiana）が挙げられるが、これらに限定されるものではない。 A plant extract containing rubusoside, and a plant extract containing at least one of stevioside, rebaudioside A and rebaudioside C can be obtained by methods generally used for plant extraction. Plants containing rubusoside include green tea (scientific name: Rubus suavissimus), and plants containing stevioside, rebaudioside A or rebaudioside C include the aforementioned Stevia (scientific name: Stevia rebaudiana) Although it is not limited to these.
甜茶（Rubus suavissimus）は、バラ科キイチゴ属に属する植物であって、中国南部で自生しており、これらの地域から容易に入手することができる。従来、甜茶抽出物は、抗アレルギー剤等として用いられている。抽出原料として使用し得る部位としては、特に限定されないが、葉部が好適である。 Rubus suavissimus is a plant belonging to the Rosaceae family, which is native to southern China and can be easily obtained from these areas. Conventionally, a persimmon tea extract is used as an antiallergic agent etc. Although it does not specifically limit as a site | part which can be used as an extraction raw material, A leaf part is suitable.
ルブソサイドを得ることのできる甜茶抽出物は、甜茶を抽出原料とし、前述したステビア抽出物と同様に抽出することで得ることができる。また、ステビオサイド、レバウディオサイドＡまたはレバウディオサイドＣを得ることのできるステビア抽出物としては、前述したステビア抽出物を好適に用いることができる。 The persimmon tea extract from which rubusoside can be obtained can be obtained by using persimmon tea as an extraction raw material and extracting it similarly to the above-mentioned stevia extract. Further, as the stevia extract from which stevioside, rebaudioside A or rebaudioside C can be obtained, the above-mentioned stevia extract can be suitably used.
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ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣ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。例えば、抽出物を展開溶媒に溶解し、シリカゲルやアルミナ等の多孔質物質、スチレン−ジビニルベンゼン共重合体やポリメタクリレート等の多孔性樹脂等を用いたカラムクロマトグラフィーに付して、ルブソサイド、ステビオサイド、レバウディオサイドＡまたはレバウディオサイドＣを含む画分を回収する方法等が挙げられる。この場合、展開溶媒は使用する固定相に応じて適宜選択すればよいが、例えば固定相としてシリカゲルを用いた順相クロマトグラフィーにより抽出物を分離する場合、展開溶媒としてはクロロホルム：メタノール＝９５：５等が挙げられる。さらに、カラムクロマトグラフィーにより得られた、ルブソサイド、ステビオサイド、レバウディオサイドＡまたはレバウディオサイドＣを含む画分を、ＯＤＳを用いた逆相シリカゲルクロマトグラフィー、再結晶、液−液向流抽出、イオン交換樹脂を用いたカラムクロマトグラフィー等の任意の有機化合物精製手段を用いて精製してもよい。 The method for isolating and purifying rubusoside, stevioside, rebaudioside A and rebaudioside C from the extract obtained as described above, the concentrate of the extract or the dried product of the extract is particularly preferred. It is not limited and can be carried out by a conventional method. For example, the extract is dissolved in a developing solvent and subjected to column chromatography using a porous substance such as silica gel or alumina, a porous resin such as styrene-divinylbenzene copolymer or polymethacrylate, etc. , Rebaudioside A or rebaudioside C, and the like. In this case, the developing solvent may be appropriately selected according to the stationary phase to be used, but when, for example, the extract is separated by normal phase chromatography using silica gel as the stationary phase, chloroform: methanol = 95: 5 mag is listed. Furthermore, reverse phase silica gel chromatography using ODS, recrystallization, liquid-liquid countercurrent extraction, and the fractions containing rubusoside, stevioside, rebaudioside A or rebaudioside C obtained by column chromatography You may refine | purify using arbitrary organic compound refinement | purification means, such as column chromatography using ion exchange resin.
なお、本実施形態にて用いるルブソサイド、ステビオサイド、レバウディオサイドＡまたはレバウディオサイドＣは、市販品を用いてもよい。 For rubusoside, stevioside, rebaudioside A or rebaudioside C used in the present embodiment, commercially available products may be used.
〔断片化コラーゲン代謝促進剤〕
以上のようにして得られるステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣは、優れたＥｎｄｏ１８０活性化作用を有しているため、断片化コラーゲン代謝促進剤の有効成分として好適である。本実施形態の断片化コラーゲン代謝促進剤は、医薬品、医薬部外品、化粧品、飲食品等の幅広い用途に使用することができる。
[Fragmented collagen metabolism promoter]
The stevia extract obtained as described above, rubusoside, stevioside, rebaudioside A and rebaudioside C have excellent Endo 180 activation activity, and thus the active ingredient of the fragmented collagen metabolism promoter Is preferred. The fragmented collagen metabolism promoter of the present embodiment can be used in a wide range of uses such as medicines, quasi-drugs, cosmetics, food and drink.
ここで、ステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣが有するＥｎｄｏ１８０活性化作用は、Ｅｎｄｏ１８０ ｍＲＮＡ発現促進作用および／またはＥｎｄｏ１８０産生促進作用に基づいて発揮される。ただし、ステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣが有するＥｎｄｏ１８０活性化作用は、上記作用に基づいて発揮されるＥｎｄｏ１８０活性化作用に限定されるものではない。 Here, Endo180 activation activity possessed by the stevia extract, rubusoside, stevioside, rebaudioside A and rebaudioside C is exerted based on Endo180 mRNA expression promoting action and / or Endo180 production promoting action. However, the Endo180 activating action possessed by the stevia extract, rubusoside, stevioside, rebaudioside A and rebaudioside C is not limited to the Endo180 activating action exerted based on the above action.
また、ステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣは、そのＥｎｄｏ１８０活性化作用、Ｅｎｄｏ１８０ ｍＲＮＡ発現促進作用またはＥｎｄｏ１８０産生促進作用を利用して、それぞれＥｎｄｏ１８０活性化剤、Ｅｎｄｏ１８０ ｍＲＮＡ発現促進剤またはＥｎｄｏ１８０産生促進剤の有効成分として使用してもよい。 In addition, Stevia extract, rubusoside, stevioside, rebaudioside A and rebaudioside C are each an Endo 180 activator, utilizing its Endo 180 activation action, Endo 180 mRNA expression promoting action or Endo 180 production promoting action, You may use as an active ingredient of Endo180 mRNA expression promoter or Endo180 production promoter.
本実施形態の断片化コラーゲン代謝促進剤は、上記Ｅｎｄｏ１８０活性化成分のみからなるものでもよいし、上記Ｅｎｄｏ１８０活性化成分を製剤化したものでもよい。 The fragmented collagen metabolism promoting agent of the present embodiment may be composed only of the above-mentioned Endo 180 activating component, or may be one in which the above Endo 180 activating component is formulated.
本実施形態の断片化コラーゲン代謝促進剤は、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。断片化コラーゲン代謝促進剤は、他の組成物（例えば、後述するシワ改善用飲食品、関節炎予防・改善用飲食品等）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 fragmented collagen metabolism promoter of the present embodiment may be a powder, granule, tablet, liquid or the like according to a conventional method using a pharmaceutically acceptable carrier such as dextrin or cyclodextrin or any other auxiliary agent. It can be formulated into any dosage form. Under the present circumstances, as an adjuvant, an excipient | filler, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring agent, etc. can be used, for example. The fragmented collagen metabolism promoter can be used by being blended with other compositions (for example, food and drink for improving wrinkles, food and drink for preventing and improving arthritis, etc. described later), ointment, external solution, patch It can be used as an agent etc.
本実施形態の断片化コラーゲン代謝促進剤を製剤化した場合、上記Ｅｎｄｏ１８０活性化成分の含有量は、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 fragmented collagen metabolism promoter of this embodiment is formulated, the content of the above-mentioned Endo 180 activating component is not particularly limited, and can be appropriately set according to the purpose.
なお、本実施形態の断片化コラーゲン代謝促進剤は、必要に応じて、断片化コラーゲン代謝促進作用を有する他の天然物由来成分等を、上記Ｅｎｄｏ１８０活性化成分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 fragmented collagen metabolism promoter of this embodiment may be used as an active ingredient by blending other natural product-derived components having fragmented collagen metabolism promoting activity, etc. together with the above-mentioned Endo 180 activating component, as necessary. Can.
本実施形態の断片化コラーゲン代謝促進剤の患者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。また、本実施形態の断片化コラーゲン代謝促進剤の投与量も、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。 As a method of administering the fragmented collagen metabolism promoting agent of the present embodiment to a patient, transdermal administration, oral administration and the like can be mentioned, but according to the type of disease, a method suitable for the prevention / treatment etc. is appropriately selected. Just do it. Further, the dose of the fragmented collagen metabolism promoter of the present embodiment may be appropriately increased or decreased depending on the type of disease, severity, individual differences of patients, administration method, administration period and the like.
本実施形態の断片化コラーゲン代謝促進剤は、有効成分である上記Ｅｎｄｏ１８０活性化成分、特にステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣが有するＥｎｄｏ１８０活性化作用、Ｅｎｄｏ１８０ ｍＲＮＡ発現促進作用またはＥｎｄｏ１８０産生促進作用を通じて、線維芽細胞においてＥｎｄｏ１８０を活性化し、これにより、エンドサイトーシスによる断片化コラーゲンの取り込みを促進して正常なコラーゲン線維構造の再生を促し、シワの形成等といった皮膚の光老化症状を予防、治療または改善することができる。また、本実施形態の断片化コラーゲン代謝促進剤は、正常なコラーゲン線維構造の再生を促すことにより、慢性関節リウマチ、変形性関節炎、化膿性関節炎、痛風性関節炎、外傷性関節炎、骨関節炎等の関節炎の予防、治療または改善などの用途に用いることができる。 The fragmented collagen metabolism promoting agent of the present embodiment is an active ingredient of the above-mentioned Endo 180 activating component, in particular Stevia extract, rubusoside, stevioside, rebaudioside A and Rebaudioside C, having an Endo 180 activating action, Endo 180 Endo180 is activated in fibroblasts through mRNA expression promoting action or Endo180 production promoting action, thereby promoting the uptake of fragmented collagen by endocytosis and promoting the regeneration of normal collagen fiber structure, formation of wrinkles, etc. It is possible to prevent, treat or ameliorate skin photoaging symptoms such as In addition, the fragmented collagen metabolism promoter of the present embodiment promotes regeneration of normal collagen fiber structure, thereby promoting rheumatoid arthritis, osteoarthritis, suppurative arthritis, gouty arthritis, traumatic arthritis, osteoarthritis, etc. It can be used for applications such as prevention, treatment or amelioration of arthritis.
なお、本実施形態の断片化コラーゲン代謝促進剤は、上述した用途以外にも、Ｅｎｄｏ１８０活性化作用、Ｅｎｄｏ１８０ ｍＲＮＡ発現促進作用またはＥｎｄｏ１８０産生促進作用を発揮することに意義のあるすべての用途に用いることができる。例えば、本実施形態の断片化コラーゲン代謝促進剤、または前述したＥｎｄｏ１８０活性化剤、Ｅｎｄｏ１８０ ｍＲＮＡ発現促進剤もしくはＥｎｄｏ１８０産生促進剤は、そのＥｎｄｏ１８０／ｕＰＡＲＡＰの活性化作用、Ｅｎｄｏ１８０ ｍＲＮＡ発現促進作用またはＥｎｄｏ１８０産生促進作用を通じて、プラスミノーゲンからのプラスミンの生成を促進することができる。 In addition, the fragmented collagen metabolism promoter of this embodiment is used for all uses that are significant in exerting the Endo180 activating action, the Endo180 mRNA expression promoting action or the Endo180 production promoting action other than the use described above. Can. For example, the fragmented collagen metabolism promoting agent of the present embodiment, or the above-mentioned Endo 180 activator, Endo 180 mRNA expression promoting agent or Endo 180 production promoting agent, has an activation effect of Endo 180 / uPARAP, an Endo 180 mRNA expression promoting effect or Endo 180 production. Through the promoting action, the production of plasmin from plasminogen can be promoted.
本実施形態の断片化コラーゲン代謝促進剤は、優れた断片化コラーゲン代謝促進作用を有するため、皮膚外用剤などの他の組成物（例えば、後述するシワ改善用組成物、シワ改善用飲食品、関節炎予防・改善用組成物、関節炎予防・改善用飲食品）に配合するのに好適である。この場合に、上記Ｅｎｄｏ１８０活性化成分、特にステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡまたはレバウディオサイドＣは、そのまま配合してもよいし、上記Ｅｎｄｏ１８０活性化成分から製剤化した断片化コラーゲン代謝促進剤を配合してもよい。 The fragmented collagen metabolism promoting agent of the present embodiment has an excellent fragmented collagen metabolism promoting action, and therefore, other compositions such as a skin external preparation (for example, a composition for improving wrinkles, food and drink for improving wrinkles described later, It is suitable for blending in a composition for preventing and improving arthritis and a food and drink for preventing and improving arthritis. In this case, the above-mentioned Endo 180 activating component, in particular Stevia extract, rubusoside, stevioside, rebaudioside A or rebaudioside C may be formulated as it is, or fragmented from the above Endo 180 activating component A collagen metabolism promoter may be blended.
また、本実施形態の断片化コラーゲン代謝促進剤は、優れた断片化コラーゲン代謝促進作用を有するので、これらの作用機構に関する研究のための試薬としても好適に利用することができる。 In addition, since the fragmented collagen metabolism promoter of the present embodiment has an excellent fragmented collagen metabolism promoting action, it can also be suitably used as a reagent for research on the mechanism of these actions.
なお、本実施形態の断片化コラーゲン代謝促進剤は、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。 Although the fragmented collagen metabolism promoter of the present embodiment is suitably applied to humans, animals other than humans (eg, mice, rats, hamsters, etc.) as long as the respective effects are exhibited. , Dogs, cats, cattle, pigs, monkeys, etc.).
〔シワ改善用組成物，関節炎予防・改善用組成物〕
上記Ｅｎｄｏ１８０活性化成分は、優れた断片化コラーゲン代謝促進作用を有しているため、シワ改善用組成物または関節炎予防・改善用組成物に配合するのに好適である。この場合、上記Ｅｎｄｏ１８０活性化成分、特にステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡまたはレバウディオサイドＣは、そのまま配合してもよいし、上記Ｅｎｄｏ１８０活性化成分から製剤化した断片化コラーゲン代謝促進剤を配合してもよい。
[Composition for improving wrinkles, composition for preventing and improving arthritis]
The above-mentioned Endo 180 activating component has an excellent fragmented collagen metabolism promoting action, and thus is suitable for being blended in a composition for improving wrinkles or a composition for preventing or improving arthritis. In this case, the above-mentioned Endo 180 activating component, in particular Stevia extract, rubusoside, stevioside, rebaudioside A or rebaudioside C may be formulated as it is, or fragmented collagen formulated from the above Endo 180 activating component A metabolism promoter may be blended.
上記Ｅｎｄｏ１８０活性化成分または断片化コラーゲン代謝促進剤を配合することにより、当該組成物にＥｎｄｏ１８０活性化作用、Ｅｎｄｏ１８０ ｍＲＮＡ発現促進作用またはＥｎｄｏ１８０産生促進作用を付与することができ、シワ改善用途、関節炎予防・改善用途に特に好適なものとすることができる。 By blending the above-mentioned Endo 180 activating component or fragmented collagen metabolism promoting agent, the composition can be imparted with Endo 180 activating action, Endo 180 mRNA expression promoting action or Endo 180 production promoting action, and use for improving wrinkles, prevention of arthritis It can be particularly suitable for improvement applications.
本実施形態に係るシワ改善用組成物および関節炎予防・改善用組成物の投与形態としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、経口、非経口、外用などが挙げられる。
また、本実施形態に係るシワ改善用組成物および関節炎予防・改善用組成物の剤型としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、錠剤、粉剤、カプセル剤、顆粒剤、エキス剤、シロップ剤等の経口投与剤；注射剤、点滴剤、坐剤等の非経口投与剤；軟膏等の外用剤などが挙げられる。
The administration form of the composition for improving wrinkles and the composition for preventing and improving arthritis according to the present embodiment is not particularly limited and can be appropriately selected according to the purpose. For example, oral, parenteral, external use, etc. It can be mentioned.
Moreover, there is no restriction | limiting in particular as a dosage form of the composition for improving wrinkles and the composition for preventing and improving arthritis according to the present embodiment, and can be appropriately selected according to the purpose. For example, tablets, powders, capsules And orally administered agents such as granules, extracts and syrups; parenterally administered agents such as injections, drips and suppositories; external agents such as ointments and the like.
本実施形態に係るシワ改善用組成物は、特に皮膚外用剤に好適に使用することができる。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る。 The composition for improving wrinkles according to this embodiment can be suitably used particularly for a skin external preparation. The external preparation for skin is not limited in its category, and widely includes skin cosmetics, quasi-drugs, medicines and the like used percutaneously.
本実施形態のシワ改善用組成物および関節炎予防・改善用組成物の剤型を経口投与剤、非経口投与剤、外用剤などとする場合は、上記Ｅｎｄｏ１８０活性化成分、特にステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣが有する断片化コラーゲン代謝促進作用を妨げない限り、通常の経口投与剤、非経口投与剤、外用剤等の製造に用いられる主剤、助剤又はその他の成分、例えば、収斂剤、殺菌・抗菌剤、美白剤、紫外線吸収剤、保湿剤、細胞賦活剤、抗炎症剤、抗酸化・活性酸素除去剤、油脂類、ロウ類、炭化水素類、脂肪酸類、アルコール類、エステル類、界面活性剤、香料等を併用してもよい。このように併用することで、より一般性のある製品となり、また、併用された他の有効成分との間の相乗作用が通常期待される以上の優れた効果をもたらすことがある。 When the dosage form of the composition for improving wrinkles and for preventing or improving arthritis of the present embodiment is an orally administered agent, a parenterally administered agent, an external preparation, etc., the above-mentioned Endo 180 activating component, particularly stevia extract, rubusoside The main agent / auxiliary agent used in the preparation of usual oral agents, parenteral agents, external preparations, etc. as long as it does not interfere with the fragmented collagen metabolism promoting effect possessed by stevioside, rebaudioside A and rebaudioside C Or other components such as astringents, bactericidal and antifungal agents, whitening agents, ultraviolet light absorbers, moisturizers, cell activators, anti-inflammatory agents, antioxidants / active oxygen scavengers, oils and fats, waxes, hydrocarbons Fatty acids, alcohols, esters, surfactants, perfumes and the like may be used in combination. Such combined use leads to a more general product, and synergy between other combined active ingredients may result in superior effects than normally expected.
また、本実施形態に係るシワ改善用組成物は、上記断片化コラーゲン代謝促進剤とともに、コラーゲン産生促進剤、血流促進剤、コラーゲン、タンパク質、ペプチドおよびアミノ酸からなる群より選ばれる１種または２種以上の成分を含有することが好ましい。これらの成分は、断片化コラーゲン代謝促進作用とは異なる観点からシワ改善効果をもたらすことができる。例えば、コラーゲン産生促進剤は、新たなコラーゲンの産生を促進することにより、上記断片化コラーゲン代謝促進剤による断片化コラーゲンの代謝促進作用と協調して、正常なコラーゲン線維構造の再生を促し、シワの形成等といった皮膚の光老化症状をより効果的に予防、治療または改善することができる。 Further, the composition for improving wrinkles according to the present embodiment is one or two selected from the group consisting of a collagen production promoter, a blood flow promoter, collagen, a protein, a peptide and an amino acid together with the fragmented collagen metabolism promoter It is preferable to contain species or more components. These components can provide a wrinkle improving effect from the viewpoint different from the fragmented collagen metabolism promoting effect. For example, by promoting the production of new collagen, the collagen production promoter promotes the regeneration of normal collagen fiber structure in coordination with the metabolism promoting action of the fragmented collagen by the above-mentioned fragmented collagen metabolism promoter, thereby promoting wrinkle formation. Can be more effectively prevented, treated or ameliorated, such as skin photoaging symptoms such as the formation of
また、本実施形態に係る関節炎予防・改善用組成物は、上記断片化コラーゲン代謝促進剤とともに、コラーゲン産生促進剤、抗炎症剤、血流促進剤、コラーゲン、タンパク質、ペプチド、アミノ酸、ブラックジンジャー、グルコサミン、Ｎ−アセチルグルコサミン、コンドロイチンから選ばれる１種または２種以上の成分を含有することが好ましい。これらの成分は、断片化コラーゲン代謝促進作用とは異なる観点から関節炎予防・改善効果をもたらすことができる。 In addition, the composition for preventing and improving arthritis according to the present embodiment includes, in addition to the fragmented collagen metabolism promoter, a collagen production promoter, an anti-inflammatory agent, a blood flow promoter, collagen, a protein, a peptide, an amino acid, black ginger, It is preferable to contain one or more components selected from glucosamine, N-acetylglucosamine, and chondroitin. These components can provide an arthritis preventing and improving effect from the viewpoint different from the fragmented collagen metabolism promoting action.
〔シワ改善用飲食品，関節炎予防・改善用飲食品〕
上記シワ改善用組成物は、上記Ｅｎｄｏ１８０活性化成分、特にステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣが有する優れた断片化コラーゲン代謝促進作用を付与すべく、シワ改善用飲食品に配合するのに好適である。同様に、上記関節炎予防・改善用組成物は、関節炎予防・改善用飲食品に配合するのに好適である。この場合、上記Ｅｎｄｏ１８０活性化成分、特にステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡまたはレバウディオサイドＣをそのまま配合してもよいし、これらの成分を製剤化した断片化コラーゲン代謝促進剤を配合してもよい。
[Food and drink for improving wrinkles, food and drink for preventing and improving arthritis]
The above-mentioned composition for improving wrinkles has wrinkles so as to impart the excellent fragmented collagen metabolism promoting action possessed by the above-mentioned Endo 180 activating component, particularly Stevia extract, rubusoside, stevioside, rebaudioside A and rebaudioside C. It is suitable for blending in food and drink for improvement. Similarly, the above-mentioned composition for preventing and / or improving arthritis is suitable for being blended in food and drink for preventing and / or improving arthritis. In this case, the above-mentioned Endo 180 activating component, in particular Stevia extract, rubusoside, stevioside, rebaudioside A or rebaudioside C may be blended as it is, or fragmented collagen metabolism promotion prepared by formulating these components An agent may be blended.
ここで、飲食品とは、人の健康に危害を加えるおそれが少なく、通常の社会生活において、経口又は消化管投与により摂取されるものをいい、行政区分上の食品、医薬品、医薬部外品等の区分に制限されるものではない。したがって、本実施形態における「シワ改善用飲食品」および「関節炎予防・改善用飲食品」は、経口的に摂取される一般食品、健康食品（機能性飲食品）、保健機能食品（特定保健用食品，栄養機能食品）、医薬部外品、医薬品等を幅広く含むものである。本実施形態に係るシワ改善用飲食品または関節炎予防・改善用飲食品は、当該飲食品またはその包装に、上記Ｅｎｄｏ１８０活性化成分、特にステビア抽出物、ルブソサイド、ステビオサイド、レバウディオサイドＡおよびレバウディオサイドＣが有する好ましい作用を表示することのできる飲食品であることが好ましく、保健機能食品（特定保健用食品，機能性表示食品，栄養機能食品）、医薬部外品および医薬品であることが特に好ましい。 Here, food and drink are items that are less likely to harm human health and are taken by oral or digestive tract administration in normal social life, and food, medicine, quasi-drugs in administrative divisions It is not limited to the classification of etc. Therefore, the “food and drink for improving wrinkles” and the “food and drink for preventing and improving arthritis” in the present embodiment are general food, health food (functional food and drink), health functional food (for specified health use) taken orally Food, nutrition functional food), quasi-drugs, medicines etc. are widely included. The food and drink for improving wrinkles or the food for preventing and ameliorating arthritis according to the present embodiment comprises the above-mentioned Endo 180 activating component, in particular Stevia extract, rubusoside, stevioside, rebaudioside A and rebaudioside A, in the food or drink or the package thereof. Foods and beverages that can display the preferable action of baudioside C are preferable, and health functional food (food for specified health, functional indication food, nutritional function food), quasi-drug and medicine Is particularly preferred.
上記シワ改善用組成物または関節炎予防・改善用組成物を飲食品に配合する場合、それらにおける有効成分の配合量は、使用目的、症状、性別等を考慮して適宜変更することができるが、添加対象となる飲食品の一般的な摂取量を考慮して、成人１日あたりの抽出物摂取量が約１〜１０００ｍｇになるようにするのが好ましい。なお、添加対象飲食品が顆粒状、錠剤状又はカプセル状の飲食品の場合、シワ改善用組成物または関節炎予防・改善用組成物の添加量は、添加対象飲食品に対して通常０．１〜１００質量％であり、好ましくは５〜１００質量％である。 When the composition for improving wrinkles or the composition for preventing or improving arthritis is blended in a food or drink, the blending amount of the active ingredient in them can be appropriately changed in consideration of the purpose of use, symptoms, sex, etc. In consideration of the general intake of the food and drink to be added, it is preferable that the extract intake per adult be about 1 to 1000 mg. When the food or drink to be added is in the form of granules, tablets or capsules, the amount of the composition for improving wrinkles or the composition for preventing or ameliorating arthritis is usually 0.1 for the food or drink to be added. And 100% by mass, preferably 5 to 100% by mass.
本実施形態のシワ改善用飲食品または関節炎予防・改善用飲食品は、上記Ｅｎｄｏ１８０活性化成分の活性を妨げないような任意の飲食品に配合したものであってもよいし、上記Ｅｎｄｏ１８０活性化成分を主成分とする栄養補助食品であってもよい。 The food and drink for improving wrinkles or the food for preventing and ameliorating arthritis of the present embodiment may be blended with any food and drink that does not interfere with the activity of the above-mentioned Endo 180 activating component, or the above Endo 180 activation It may be a dietary supplement containing an ingredient as its main component.
本実施形態のシワ改善用飲食品または関節炎予防・改善用飲食品を製造する際には、例えば、デキストリン、デンプン等の糖類；ゼラチン、大豆タンパク、トウモロコシタンパク等のタンパク質；アラニン、グルタミン、イソロイシン等のアミノ酸類；セルロース、アラビアゴム等の多糖類；大豆油、中鎖脂肪酸トリグリセリド等の油脂類などの任意の助剤を添加して任意の形状の飲食品にすることができる。 In the case of producing the food and drink for improving wrinkles or the food for preventing and improving arthritis of the present embodiment, for example, saccharides such as dextrin and starch; proteins such as gelatin, soybean protein and corn protein; alanine, glutamine, isoleucine and the like Amino acids; polysaccharides such as cellulose and gum arabic; oils and fats such as soybean oil and medium-chain fatty acid triglyceride and the like;
上記シワ改善用組成物または関節炎予防・改善用組成物を配合し得る飲食品は特に限定されないが、その具体例としては、清涼飲料、炭酸飲料、栄養飲料、果実飲料、乳酸飲料等の飲料（これらの飲料の濃縮原液及び調整用粉末を含む）；アイスクリーム、アイスシャーベット、かき氷等の冷菓；そば、うどん、はるさめ、ぎょうざの皮、しゅうまいの皮、中華麺、即席麺等の麺類；飴、チューインガム、キャンディー、ガム、チョコレート、錠菓、スナック菓子、ビスケット、ゼリー、ジャム、クリーム、焼き菓子等の菓子類；かまぼこ、ハム、ソーセージ等の水産・畜産加工食品；加工乳、発酵乳等の乳製品；サラダ油、てんぷら油、マーガリン、マヨネーズ、ショートニング、ホイップクリーム、ドレッシング等の油脂及び油脂加工食品；ソース、たれ等の調味料；スープ、シチュー、サラダ、惣菜、漬物；その他種々の形態の健康・栄養補助食品；錠剤、カプセル剤、ドリンク剤などが挙げられる。これらの飲食品に上記シワ改善用組成物または関節炎予防・改善用組成物を配合するときには、通常用いられる補助的な原料や添加物を併用することができる。 Although the food and drink that can be blended with the composition for improving wrinkles or the composition for preventing and improving arthritis are not particularly limited, specific examples thereof include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks and the like Ice cream, ice sorbet, frozen ice such as shaved ice; buckwheat noodles, udon, radish, grated skin, shumai skin, Chinese noodles, instant noodles, etc .; Sweets such as chewing gum, candies, gums, chocolate, confections, snacks, biscuits, jellies, jams, creams and baked confections; Fisheries / livestock processed foods such as kamabo, ham and sausages; dairy products such as processed milk and fermented milk Oils, fats and oils processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing ; Source, condiments such as sauce; soups, stews, salads, prepared foods, pickles; Other health and dietary supplements in various forms; tablets, capsules, and the like drinks. When blending the composition for improving wrinkles or the composition for preventing or improving arthritis with these food and drink, auxiliary raw materials and additives which are usually used can be used in combination.
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、ステビア抽出物（製品名「純マルミロン」，丸善製薬社製，試料１）、ルブソサイド（丸善製薬社製，試料２）、ステビオサイド（丸善製薬社製，試料３）、レバウディオサイドＣ（丸善製薬社製，試料４）、およびレバウディオサイドＡ（丸善製薬社製，試料５）を使用した。 Hereinafter, the present invention will be specifically described by showing test examples, but the present invention is not limited to the following examples. In the following test examples, Stevia extract (product name "pure marmilon", manufactured by Maruzen Pharmaceutical, sample 1), rubusoside (manufactured by Maruzen Pharmaceutical, sample 2), stevioside (manufactured by Maruzen Pharmaceutical), as test samples. Sample 3), rebaudioside C (manufactured by Maruzen Pharmaceutical, sample 4), and rebaudioside A (manufactured by Maruzen Pharmaceutical, sample 5) were used.
〔試験例１〕Ｅｎｄｏ１８０ ｍＲＮＡ発現促進作用試験
上記天然物由来成分（試料１〜５）について、以下のようにしてＥｎｄｏ１８０ ｍＲＮＡ発現促進作用を試験した。
Test Example 1 Endo180 mRNA Expression Promoting Action Test The above natural product-derived components (samples 1 to 5) were tested for Endo180 mRNA expression promoting action as follows.
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の細胞密度になるようにＦＢＳ不含有ダルベッコＭＥＭで希釈した後、６ウェルマイクロプレートに１ウェル当たり２ｍＬずつ播種し、一晩培養した。 Human normal skin fibroblasts (NB1 RGB) were cultured using Dulbecco's MEM containing 10% FBS, and then cells were harvested by trypsinization. The collected cells were diluted with FBS-free Dulbecco's MEM to a cell density of 1.0 × 10 5 cells / mL, and then 2 mL per well were seeded in a 6-well microplate and cultured overnight.
培養終了後、培地を除去し、ＦＢＳ不含有ダルベッコＭＥＭに溶解した被験試料（試料１〜５，試料濃度は下記表１を参照）を各ウェルに２ｍＬ添加し、２４時間培養した。なお、コントロールとして、試料無添加のＦＢＳ不含有ダルベッコＭＥＭを用いて同様に培養した。培養後、培地を除去し、ＩＳＯＧＥＮ II（ニッポンジーン社製，Cat. No. 311-07361）にて総ＲＮＡを抽出し、それぞれのＲＮＡ量を分光光度計にて測定し、１００ng/μLになるように総ＲＮＡを調製した。 After completion of the culture, the medium was removed, and 2 mL of a test sample (samples 1 to 5, sample concentration see Table 1 below) dissolved in Dulbecco's MEM without FBS was added to each well and cultured for 24 hours. In addition, it culture | cultivated similarly using FBS non-containing Dulbecco MEM which does not have a sample addition as a control. After culture, the medium is removed, total RNA is extracted with ISOGEN II (Nippon Gene, Cat. No. 311-07361), and the amount of each RNA is measured with a spectrophotometer so as to be 100 ng / μL. Total RNA was prepared.
この総ＲＮＡを鋳型とし、Ｅｎｄｏ１８０および内部標準であるＧＡＰＤＨについて、ｍＲＮＡの発現量を測定した。検出はリアルタイムＰＣＲ装置Smart Cycler（Cepheid社製）を用いて、TaKaRa SYBR PrimeScriptTM RT-PCR Kit（Perfect Real Time）（code No. RR063A）によるリアルタイム2 Step ＲＴ−ＰＣＲ反応により行った。Ｅｎｄｏ１８０ ｍＲＮＡの発現量は、「被験試料添加」および「被験試料無添加」にてそれぞれ培養した細胞から調製した総ＲＮＡ標品を基にして、ＧＡＰＤＨの値で補正値を求めた。得られた値から、下記式によりＥｎｄｏ１８０ ｍＲＮＡ発現促進率（％）を算出した。 Using this total RNA as a template, the expression level of mRNA was measured for Endo 180 and GAPDH as an internal standard. Detection using real-time PCR device Smart Cycler (Cepheid, Inc.), was performed by real-time 2 Step RT-PCR reaction with TaKaRa SYBR PrimeScript TM RT-PCR Kit (Perfect Real Time) (code No. RR063A). The expression level of Endo180 mRNA was determined based on the total RNA preparation prepared from the cells cultured respectively with “test sample addition” and “no test sample addition”, and the correction value was determined using the GAPDH value. From the obtained values, the Endo 180 mRNA expression promotion rate (%) was calculated by the following formula.
Ｅｎｄｏ１８０ ｍＲＮＡ発現促進率（％）＝Ａ／Ｂ×１００
式中の各項はそれぞれ以下を表す。
Ａ：被験試料添加での補正値
Ｂ：被験試料無添加での補正値
結果を表１に示す。
Endo 180 mRNA expression promotion rate (%) = A / B × 100
Each term in the formula represents the following.
A: Correction value for test sample addition B: Correction value for no test sample addition The results are shown in Table 1.
表１に示すように、ステビア抽出物（試料１）、ルブソサイド（試料２）、ステビオサイド（試料３）、レバウディオサイドＣ（試料４）、およびレバウディオサイドＡ（試料５）は、いずれも優れたＥｎｄｏ１８０ ｍＲＮＡ発現促進作用を有することが確認された。 As shown in Table 1, Stevia extract (sample 1), rubusoside (sample 2), stevioside (sample 3), rebaudioside C (sample 4), and rebaudioside A (sample 5) It was also confirmed that it has an excellent Endo180 mRNA expression promoting action.
〔試験例２〕Ｅｎｄｏ１８０産生促進作用試験
上記天然物由来成分（試料１〜５）について、以下のようにしてＥｎｄｏ１８０産生促進作用を試験した。
Test Example 2 Endo180 Production Promoting Action Test The above-described natural product-derived components (samples 1 to 5) were tested for Endo 180 production promoting action as follows.
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の細胞密度になるようＦＢＳ不含有ダルベッコＭＥＭで希釈した後、９６ウェルマイクロプレートに１ウェル当たり１００μＬずつ播種し、一晩培養した。 Human normal skin fibroblasts (NB1 RGB) were cultured using Dulbecco's MEM containing 10% FBS, and then cells were harvested by trypsinization. The collected cells were diluted with Dulbecco's MEM without FBS to a cell density of 1.0 × 10 5 cells / mL, and then 100 μL per well was seeded in a 96-well microplate and cultured overnight.
培養終了後、培地を除去し、ＦＢＳ不含有ダルベッコＭＥＭに溶解した被験試料（試料１〜５，試料濃度は下記表２を参照）を各ウェルに１００μＬずつ添加し、２４時間培養した。なお、コントロールとして、試料無添加のＦＢＳ不含有ダルベッコＭＥＭを用いて同様に培養した。培養終了後、各ウェルの細胞表面に存在するＥｎｄｏ１８０量をＥＬＩＳＡ法により測定した。また、Ｅｎｄｏ１８０リコンビナントタンパクを用いて検量線を作成し、Ｅｎｄｏ１８０産生量を計算した。測定結果から、下記式によりＥｎｄｏ１８０産生促進率（％）を算出した。 After completion of the culture, the medium was removed, and 100 μL each of a test sample (samples 1 to 5, sample concentration see Table 2 below) dissolved in Dulbecco's MEM without FBS was added to each well and cultured for 24 hours. In addition, it culture | cultivated similarly using FBS non-containing Dulbecco MEM which does not have a sample addition as a control. After completion of the culture, the amount of Endo 180 present on the cell surface of each well was measured by ELISA. In addition, a standard curve was prepared using Endo180 recombinant protein, and the amount of production of Endo180 was calculated. From the measurement results, Endo 180 production promotion rate (%) was calculated by the following equation.
Ｅｎｄｏ１８０産生促進率（％）＝Ａ／Ｂ×１００
式中の各項はそれぞれ以下を表す。
Ａ：被験試料添加でのＥｎｄｏ１８０産生量
Ｂ：試料無添加でのＥｎｄｏ１８０産生量
Endo 180 production promotion rate (%) = A / B x 100
Each term in the formula represents the following.
A: Endo 180 production amount with addition of test sample B: Endo 180 production amount without addition of sample
さらに、Ｈｏｅｃｈｓｔ ３３３４２を用いて核染色を行い、細胞数測定のため蛍光量を測定した。細胞あたりのＥｎｄｏ１８０産生量は、検量線を用いて計算したＥｎｄｏ１８０産生量を、Ｈｏｅｃｈｓｔ ３３３４２の蛍光波長（Ｅｘ：３５０ｎｍ／Ｅｍ：４６０ｎｍ）値で割ることで補正値を算出した。得られた補正値に基づき、下記式により、細胞あたりのＥｎｄｏ１８０産生促進率（％）を算出した。 Furthermore, nuclear staining was performed using Hoechst 33342, and the amount of fluorescence was measured for cell number measurement. The correction value was calculated by dividing the amount of Endo180 production calculated using the calibration curve by the fluorescence wavelength (Ex: 350 nm / Em: 460 nm) value of Hoechst 33342 for the amount of Endo 180 production per cell. Based on the obtained correction value, the Endo 180 production promotion rate (%) per cell was calculated by the following formula.
細胞あたりのＥｎｄｏ１８０産生促進率（％）＝Ｃ／Ｄ×１００
式中の各項はそれぞれ以下を表す。
Ｃ ：被験試料添加における細胞あたりのＥｎｄｏ１８０産生量
Ｄ ：被験試料無添加における細胞あたりのＥｎｄｏ１８０産生量
結果を表２および表３に示す。
Endo 180 production promotion rate per cell (%) = C / D × 100
Each term in the formula represents the following.
C: Endo180 production per cell in the test sample addition D: Endo180 production per cell in the absence of the test sample The results are shown in Table 2 and Table 3.
表２および表３に示すように、ステビア抽出物（試料１）、ルブソサイド（試料２）、ステビオサイド（試料３）、レバウディオサイドＣ（試料４）、およびレバウディオサイドＡ（試料５）は、いずれも優れたＥｎｄｏ１８０産生促進作用を有することが確認された。 As shown in Tables 2 and 3, Stevia extract (sample 1), rubusoside (sample 2), stevioside (sample 3), rebaudioside C (sample 4), and rebaudioside A (sample 5) All were confirmed to have excellent Endo 180 production promoting activity.
〔配合例１〕
下記組成に従い、乳液を常法により製造した。
ステビア抽出物 ０．０１ｇ
ホホバオイル ４．００ｇ
１，３−ブチレングリコール ３．００ｇ
アルブチン ３．００ｇ
ポリオキシエチレンセチルエーテル（20E.O.） ２．５０ｇ
オリーブオイル ２．００ｇ
スクワラン ２．００ｇ
セタノール ２．００ｇ
モノステアリン酸グリセリル ２．００ｇ
オレイン酸ポリオキシエチレンソルビタン（20E.O.） ２．００ｇ
パラオキシ安息香酸メチル ０．１５ｇ
グリチルリチン酸ステアリル ０．１０ｇ
黄杞エキス ０．１０ｇ
グリチルリチン酸ジカリウム ０．１０ｇ
イチョウ葉エキス ０．１０ｇ
コンキオリン ０．１０ｇ
オウバクエキス ０．１０ｇ
カミツレエキス ０．１０ｇ
香料 ０．０５ｇ
精製水 残部（全量を１００ｇとする）
[Composition example 1]
An emulsion was prepared by a conventional method according to the following composition.
Stevia extract 0.01 g
Jojoba oil 4.00 g
1,3-butylene glycol 3.00 g
Arbutin 3.00 g
Polyoxyethylene cetyl ether (20E.O.) 2.50 g
Olive oil 2.00 g
Squalane 2.00 g
Settle 2.00 g
Glyceryl monostearate 2.00 g
2.00 g of polyoxyethylene sorbitan oleate (20E.O.)
Methyl parahydroxybenzoate 0.15 g
Stearyl glycyrrhizinate 0.10 g
Jaundice extract 0.10 g
0.10 g of dipotassium glycyrrhizinate
Ginkgo biloba extract 0.10 g
Conchiolin 0.10 g
Oobaku extract 0.10 g
Chamomile extract 0.10 g
0.05 g of perfume
The remainder of the purified water (total amount is 100 g)
〔配合例２〕
下記組成のクリームを常法により製造した。
ルブソサイド ０．０５ｇ
クジンエキス ０．１ｇ
オウゴンエキス ０．１ｇ
流動パラフィン ５．０ｇ
サラシミツロウ ４．０ｇ
スクワラン １０．０ｇ
セタノール ３．０ｇ
ラノリン ２．０ｇ
ステアリン酸 １．０ｇ
オレイン酸ポリオキシエチレンソルビタン（20E.O.） １．５ｇ
モノステアリン酸グリセリル ３．０ｇ
油溶性甘草エキス ０．１ｇ
１，３−ブチレングリコール ６．０ｇ
パラオキシ安息香酸メチル １．５ｇ
香料 ０．１ｇ
精製水 残部（全量を１００ｇとする）
[Composition example 2]
The cream of the following composition was manufactured by a conventional method.
Rubusoside 0.05 g
Kujin Extract 0.1g
Ougon extract 0.1 g
Liquid paraffin 5.0g
Sarashi bee wax 4.0g
Squaran 10.0g
Settanol 3.0g
Lanolin 2.0g
Stearic acid 1.0 g
Polyoxyethylene sorbitan oleate (20E.O.) 1.5 g
Glyceryl monostearate 3.0 g
Oil-soluble licorice extract 0.1 g
1,3-butylene glycol 6.0 g
Methyl parahydroxybenzoate 1.5 g
Flavoring 0.1g
The remainder of the purified water (total amount is 100 g)
〔配合例３〕
下記組成の美容液を常法により製造した。
ステビオサイド ０．０１ｇ
カミツレエキス ０．１ｇ
ニンジンエキス ０．１ｇ
キサンタンガム ０．３ｇ
ヒドロキシエチルセルロース ０．１ｇ
カルボキシビニルポリマー ０．１ｇ
１，３−ブチレングリコール ４．０ｇ
グリチルリチン酸ジカリウム ０．１ｇ
グリセリン ２．０ｇ
水酸化カリウム ０．２５ｇ
香料 ０．０１ｇ
防腐剤（パラオキシ安息香酸メチル） ０．１５ｇ
エタノール ２．０ｇ
精製水 残部（全量を１００ｇとする）
[Composition example 3]
A cosmetic solution of the following composition was produced by a conventional method.
Stevioside 0.01 g
Chamomile extract 0.1 g
Carrot extract 0.1g
0.3 g of xanthan gum
Hydroxyethyl cellulose 0.1 g
Carboxy vinyl polymer 0.1 g
1,3-butylene glycol 4.0 g
0.1 g of dipotassium glycyrrhizinate
Glycerin 2.0 g
Potassium hydroxide 0.25 g
0.01 g of perfume
Preservative (methyl parahydroxybenzoate) 0.15 g
Ethanol 2.0 g
The remainder of the purified water (total amount is 100 g)
〔配合例４〕
下記組成のヘアトニックを常法により製造した。
レバウディオサイドＡ ０．４ｇ
酢酸トコフェロール 適量
セファラチン ０．００２ｇ
イソプロピルメチルフェノール ０．１ｇ
ヒアルロン酸ナトリウム ０．１５ｇ
グリセリン １５．０ｇ
エタノール １５．０ｇ
香料 適量
キレート剤（エデト酸ナトリウム） 適量
防腐剤（ヒノキチオール） 適量
可溶化剤（ポリオキシエチレンセチルエーテル） 適量
精製水 残部（全量を１００ｇとする）
[Composition Example 4]
The hair tonic of the following composition was manufactured by a conventional method.
Rebaudioside A 0.4g
Tocopheryl acetate appropriate amount Cephalatin 0.002 g
Isopropyl methyl phenol 0.1 g
Sodium hyaluronate 0.15 g
15.0 g of glycerin
15.0 g of ethanol
Fragrance Appropriate amount Chelating agent (sodium edetate) Appropriate amount Preservative (Hinokitiol) Appropriate amount Solubilizing agent (polyoxyethylene cetyl ether) Appropriate amount Purified water Remainder (total amount is 100 g)
〔配合例５〕
下記組成のシャンプーを常法により製造した。
レバウディオサイドＣ ０．５ｇ
マジョラム抽出物 １．０ｇ
ウメ果実部抽出物 ０．２ｇ
ヤシ油脂肪酸メチルタウリンナトリウム １０．０ｇ
ヤシ油脂肪酸アミドプロピルベタイン １０．０ｇ
ポリオキシエチレンアルキルエーテル硫酸ナトリウム ２０．０ｇ
ヤシ油脂肪酸ジエタノールアミド ４．０ｇ
プロピレングリコール ２．０ｇ
香料 適量
精製水 残部（全量を１００ｇとする）
[Composition Example 5]
The shampoo of the following composition was manufactured by a conventional method.
Rebaudioside C 0.5 g
Marjoram extract 1.0 g
Japanese plum extract extract 0.2g
Coconut oil fatty acid methyl taurine sodium 10.0 g
Coconut oil fatty acid amidopropyl betaine 10.0 g
Polyoxyethylene alkyl ether sodium sulfate 20.0 g
Coconut oil fatty acid diethanolamide 4.0g
Propylene glycol 2.0 g
Fragrances Appropriate amount Refined water remainder (total amount is 100 g)
〔配合例６〕
常法により、以下の組成を有する錠剤を製造した。
ステビア抽出物 ５．０ｍｇ
ドロマイト（カルシウム20％、マグネシウム10％含有） ８３．４ｍｇ
カゼインホスホペプチド １６．７ｍｇ
ビタミンＣ ３３．４ｍｇ
マルチトール １３６．８ｍｇ
コラーゲン １２．７ｍｇ
ショ糖脂肪酸エステル １２．０ｍｇ
[Composition Example 6]
In a conventional manner, tablets having the following composition were produced.
Stevia extract 5.0 mg
Dolomite (containing 20% calcium and 10% magnesium) 83.4 mg
Casein phosphopeptide 16.7 mg
Vitamin C 33.4 mg
Maltitol 136.8 mg
12.7 mg of collagen
Sucrose fatty acid ester 12.0 mg
〔配合例７〕
常法により、以下の組成を有する経口液状製剤を製造した。
＜１アンプル（１本１００ｍＬ）中の組成＞
レバウディオサイドＡ ０．３質量％
ヒハツエキス ０．１５質量％
ソルビット １２．０質量％
安息香酸ナトリウム ０．１質量％
香料 １．０質量％
硫酸カルシウム ０．５質量％
精製水 残部（１００質量％）
[Composition Example 7]
An oral liquid preparation having the following composition was produced by a conventional method.
<Composition in 1 ampoule (100 mL per bottle)>
Rebaudioside A 0.3% by mass
Hihatsu extract 0.15 mass%
Solbit 12.0 mass%
Sodium benzoate 0.1% by mass
Fragrance 1.0% by mass
Calcium sulfate 0.5 mass%
The remainder of purified water (100% by mass)
本発明の断片化コラーゲン代謝促進剤は、シワの形成等といった皮膚の光老化症状の予防、治療または改善；各種関節炎の予防、治療または改善；などに大きく貢献できる。 The fragmented collagen metabolism promoter of the present invention can greatly contribute to the prevention, treatment or amelioration of photoaging conditions of the skin such as formation of wrinkles; prevention, treatment or amelioration of various types of arthritis, and the like.
Claims (9)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPH06192114A (en) * | 1991-01-25 | 1994-07-12 | Suntory Ltd | Medicine comprising extract of hydrangeae dulcis folium as active ingredient and food and cosmetic containing the same blended therein |
| JP2004175734A (en) * | 2002-11-28 | 2004-06-24 | Kose Corp | Dermopathy inhibitor, dermopathy-improving agent, and skin care preparation for external use containing them |
| JP2011126795A (en) * | 2009-12-16 | 2011-06-30 | Maruzen Pharmaceut Co Ltd | Type i collagen production promoter |
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| JP6192114B2 (en) | 2014-06-26 | 2017-09-06 | 東芝三菱電機産業システム株式会社 | Test method and apparatus for transducer |
| JP7489079B2 (en) * | 2017-09-11 | 2024-05-23 | 丸善製薬株式会社 | A new collagen recycling promoter |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06192114A (en) * | 1991-01-25 | 1994-07-12 | Suntory Ltd | Medicine comprising extract of hydrangeae dulcis folium as active ingredient and food and cosmetic containing the same blended therein |
| JP2004175734A (en) * | 2002-11-28 | 2004-06-24 | Kose Corp | Dermopathy inhibitor, dermopathy-improving agent, and skin care preparation for external use containing them |
| JP2011126795A (en) * | 2009-12-16 | 2011-06-30 | Maruzen Pharmaceut Co Ltd | Type i collagen production promoter |
Non-Patent Citations (1)
| Title |
|---|
| STEFANIE TANG ET AL.: "UV-mediated downregulation of the endocytic collagen receptor, Endo180, contributes to accumulation", JOURNAL OF DERMATOLOGICAL SCIENCE, vol. 70, JPN6018023100, 2013, pages 42 - 48, ISSN: 0004576939 * |
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| JP2022111283A (en) * | 2017-09-11 | 2022-07-29 | 丸善製薬株式会社 | Novel collagen reuse promoting effect agent |
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