JP2021109831A - Telangiectasia inhibitor - Google Patents
Telangiectasia inhibitor Download PDFInfo
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- JP2021109831A JP2021109831A JP2020000262A JP2020000262A JP2021109831A JP 2021109831 A JP2021109831 A JP 2021109831A JP 2020000262 A JP2020000262 A JP 2020000262A JP 2020000262 A JP2020000262 A JP 2020000262A JP 2021109831 A JP2021109831 A JP 2021109831A
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- extract
- borage
- endothelin
- receptor
- kudzu
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Images
Abstract
Description
本発明は、ルリジサ又はクズの抽出物を含有することを特徴とするエンドセリンＢ受容体発現抑制剤、毛細血管拡張抑制剤、肌の赤み改善剤に関するものである。 The present invention relates to an endothelin B receptor expression inhibitor, a telangiectasia inhibitor, and a skin redness improving agent, which are characterized by containing an extract of borage or kudzu.
エンドセリンは、内皮細胞由来のペプチドホルモンで、受容体を通して種々の細胞や組織に作用する。例えば、血管平滑筋細胞等において細胞内カルシウム濃度上昇を引き起こし、血管収縮作用を有することが知られている（非特許文献１及び２、特許文献１）。各受容体がもつ生理作用は多彩ではあるが、基本的にエンドセリンＡ受容体は血管収縮作用、強心作用、中枢交感神経活性の亢進、副腎でのアルドステロン・カテコラミン分泌促進を介して血圧上昇と体液貯留を引き起こす。それに対し、エンドセリンＢ受容体は血管平滑筋と副腎皮質細胞を除くほとんどの部位でエンドセリンＡ受容体と拮抗する挙動を示し、全体として血圧低下と利尿促進作用を示す（非特許文献３）。 Endothelin is an endothelial cell-derived peptide hormone that acts on various cells and tissues through its receptors. For example, it is known that it causes an increase in intracellular calcium concentration in vascular smooth muscle cells and has a vasoconstrictive action (Non-Patent Documents 1 and 2 and Patent Document 1). Although the physiological actions of each receptor are diverse, endothelin A receptors basically increase blood pressure and fluid through vasoconstriction, cardiotonic action, enhancement of central sympathetic nerve activity, and promotion of aldosterone / catecholamine secretion in the adrenal gland. Causes retention. On the other hand, the endothelin B receptor behaves to antagonize the endothelin A receptor at most sites except vascular smooth muscle and adrenocortical cells, and exhibits a blood pressure lowering and diuretic promoting effect as a whole (Non-Patent Document 3).
動脈や静脈等の血管は通常、内腔を一層に覆う血管内皮細胞とその周囲を取り巻き血管構造の支持や血管の弛緩収縮等を司る壁細胞（平滑筋細胞及びペリサイト）から構成されている。それに対し、毛細血管は平滑筋細胞をもたず血管内皮細胞で構成されている（非特許文献４）。エンドセリンＢ受容体は平滑筋細胞においてはエンドセリンＡ受容体と同様に血管収縮作用を示すが、血管内皮細胞においては血管拡張作用を示す（非特許文献３及び５）。又、血管内皮細胞にはエンドセリンＡ受容体は存在しないため、エンドセリン／エンドセリン受容体経路を介した血管の収縮弛緩にはエンドセリンＢ受容体のみが関与している（非特許文献３）。そのため、血管内皮細胞しかもたない毛細血管においてはエンドセリン／エンドセリンＢ受容体経路を介して血管拡張が起こる。 Blood vessels such as arteries and veins are usually composed of vascular endothelial cells that further cover the lumen and wall cells (smooth muscle cells and pericite) that surround the lumen and control the support of vascular structures and the relaxation and contraction of blood vessels. .. On the other hand, capillaries do not have smooth muscle cells and are composed of vascular endothelial cells (Non-Patent Document 4). The endothelin B receptor exhibits a vasoconstrictive effect in smooth muscle cells like the endothelin A receptor, but exhibits a vasodilatory effect in vascular endothelial cells (Non-Patent Documents 3 and 5). Moreover, since endothelin A receptor does not exist in vascular endothelial cells, only endothelin B receptor is involved in the contraction and relaxation of blood vessels via the endothelin / endothelin receptor pathway (Non-Patent Document 3). Therefore, in capillaries with only vascular endothelial cells, vasodilation occurs via the endothelin / endothelin B receptor pathway.
色むらはシミやソバカス、ニキビ等に代表され、日本人女性の肌悩みの上位を占め、化粧品や美容医療分野で重要な研究対象となっている。色むらには、シミやソバカスのようにメラニン色素を要因とする色むらと、ニキビの炎症に代表されるヘモグロビンを要因とする色むらが混在している（非特許文献６）。前者は肌のくすみ、後者は肌の赤みとされている。 Color unevenness is represented by spots, freckles, acne, etc., and occupies the top ranks of skin problems of Japanese women, and is an important research target in the fields of cosmetics and aesthetic medicine. The color unevenness includes color unevenness caused by melanin pigment such as spots and freckles, and color unevenness caused by hemoglobin represented by inflammation of acne (Non-Patent Document 6). The former is considered to be dull skin and the latter is considered to be reddish skin.
肌の赤みは、ウイルスやアレルゲンに対するバリア機能が低下することにより、免疫反応が起こりやすく、炎症が引き起こされて皮膚中の毛細血管が拡張することにより生じる。又、敏感肌の肌トラブルとして赤みを挙げた人は血流量が多く、いくつもの細い血管が確認されている。更に、赤ら顔と血管新生因子（ＶＥＧＦＡ）との関連が指摘されている。欧米人に見られる赤ら顔、特に酒さは皮脂分泌過剰による脂漏性皮膚炎、及びそれぞれが引き起こす毛細血管拡張が一因であるといわれている（非特許文献７）。エンドセリンＢ受容体に着目した先行研究として、ヒトケラチノサイトがエンドセリンを産生分泌し、ヒトメラノサイトへの強力な増殖促進効果を、エンドセリンＢ受容体を介して発揮してシミを引き起こすといった知見がある（非特許文献８）。しかし、肌の赤みに対する効果については研究されていない。 Redness of the skin is caused by a decrease in the barrier function against viruses and allergens, which makes it easier for an immune response to occur, causing inflammation and dilating capillaries in the skin. In addition, those who cited redness as a skin problem with sensitive skin have a large amount of blood flow, and several small blood vessels have been confirmed. Furthermore, the relationship between reddish face and angiogenic factor (VEGFA) has been pointed out. It is said that the reddish face seen in Westerners, especially rosacea, is partly due to seborrheic dermatitis due to excessive sebum secretion and telangiectasia caused by each (Non-Patent Document 7). As a previous study focusing on the endothelin B receptor, there is a finding that human keratinocytes produce and secrete endothelin and exert a strong growth-promoting effect on human melanocytes through the endothelin B receptor to cause stains (non-endothelin B receptor). Patent Document 8). However, its effect on skin redness has not been studied.
ルリジサはムラサキ科ボラゴ属の植物でハーブの一種であり、学名：Ｂｏｒａｇｏ ｏｆｆｉｃｉｎａｌｉｓである。原産はヨーロッパ中部の地中海沿岸である。今までに、ルリジサの抽出物を有効成分として含有することを特徴とする美白剤、抗シワ剤、抗老化剤及び皮膚化粧料（特許文献２）、保湿剤及び皮膚化粧料（特許文献３）等が知られている。しかしながら、ルリジサの抽出物を有効成分として含有することを特徴とするエンドセリンＢ受容体発現抑制剤、毛細血管拡張抑制剤、肌の赤み改善剤については知られていない。 Borage is a plant of the genus Borage of the family Borage, a kind of herb, and has a scientific name: Borago officinalis. It is native to the Mediterranean coast of central Europe. So far, whitening agents, anti-wrinkle agents, anti-aging agents and skin cosmetics (Patent Document 2), moisturizers and skin cosmetics (Patent Document 3), which are characterized by containing an extract of Rurijisa as an active ingredient. Etc. are known. However, an endothelin B receptor expression inhibitor, a telangiectasia inhibitor, and a skin redness improving agent, which are characterized by containing an extract of borage as an active ingredient, are not known.
クズはマメ科クズ属のつる性の多年草であり、学名：Ｐｕｅｒａｒｉａ ｌｏｂａｔａであるが、今までに、クズの抽出物を有効成分として含有することを特徴とする美白剤、抗酸化剤及び皮膚化粧料（特許文献４）、シワ改善組成物、老化防止組成物及び皮膚外用組成物（特許文献５）等が知られている。しかしながら、クズの抽出物を有効成分として含有することを特徴とするエンドセリンＢ受容体発現抑制剤、毛細血管拡張抑制剤、肌の赤み改善剤については知られていない。 Kudzu is a climbing perennial plant belonging to the genus Kudzu of the family Leguminosae, and has a scientific name: Pueraria montana. Materials (Patent Document 4), wrinkle improving composition, antiaging composition, skin external composition (Patent Document 5) and the like are known. However, an endothelin B receptor expression inhibitor, a telangiectasia inhibitor, and a skin redness improving agent, which are characterized by containing an extract of kudzu as an active ingredient, are not known.
本発明が解決する課題は、エンドセリンＢ受容体発現を抑制する植物由来成分を見出し、これを有効成分とする、作用点が明確であり、且つ優れたエンドセリンＢ受容体発現抑制剤、毛細血管拡張抑制剤、肌の赤み改善剤を提供することである。 The problem to be solved by the present invention is to find a plant-derived component that suppresses endothelin B receptor expression, and to use this as an active ingredient, a clear-point of action and an excellent endothelin B receptor expression inhibitor, telangiectasia. It is to provide an inhibitor and a redness improving agent for the skin.
本発明者らは、上記課題の解決に向け鋭意検討を行った結果、ルリジサ又はクズの抽出物に優れたエンドセリンＢ受容体発現抑制作用を有することを見出した。更に、本発明者らは、ルリジサ又はクズの抽出物を含有する組成物に、優れたエンドセリンＢ受容体発現抑制効果、毛細血管拡張抑制効果、及び肌の赤み改善効果を見出し、本発明を完成するに至った。 As a result of diligent studies aimed at solving the above problems, the present inventors have found that an extract of borage or kudzu has an excellent endothelin B receptor expression inhibitory effect. Furthermore, the present inventors have found an excellent endothelin B receptor expression inhibitory effect, telangiectasia inhibitory effect, and skin redness improving effect in a composition containing an extract of borage or kudzu, and completed the present invention. I came to do it.
即ち、本発明は、ルリジサ又はクズの抽出物を有効成分として含有することを特徴とするエンドセリンＢ受容体発現抑制剤、毛細血管拡張抑制剤、及び肌の赤み改善剤に関する。 That is, the present invention relates to an endothelin B receptor expression inhibitor, a telangiectasia inhibitor, and a skin redness improving agent, which are characterized by containing an extract of borage or kudzu as an active ingredient.
本発明は、以下の発明を包含する。
（１）ルリジサ及び／又はクズの抽出物を含有することを特徴とするエンドセリンＢ受容体発現抑制剤。
（２）血管内皮細胞におけるエンドセリンＢ受容体発現を抑制する請求項１記載のエンドセリンＢ受容体発現抑制剤。
（３）ルリジサ及び／又はクズの抽出物を含有することを特徴とする毛細血管拡張抑制剤。
（４）ルリジサ及び／又はクズの抽出物を含有することを特徴とする肌の赤み改善剤。
The present invention includes the following inventions.
(1) An endothelin B receptor expression inhibitor containing an extract of borage and / or kudzu.
(2) The endothelin B receptor expression inhibitor according to claim 1, which suppresses endothelin B receptor expression in vascular endothelial cells.
(3) A telangiectasia inhibitor containing an extract of borage and / or kudzu.
(4) A skin redness improving agent containing an extract of borage and / or debris.
本発明のルリジサ又はクズの抽出物は、エンドセリンＢ受容体発現抑制効果に優れていた。又、この抽出物を含有することを特徴とするエンドセリンＢ受容体発現抑制剤、毛細血管拡張抑制剤、肌の赤み改善剤は、安全で、毛細血管拡張予防又は肌の赤み改善効果に優れていた。 The extract of borage or kudzu of the present invention was excellent in the effect of suppressing the expression of endothelin B receptor. Further, the endothelin B receptor expression inhibitor, the telangiectasia inhibitor, and the skin redness improving agent, which are characterized by containing this extract, are safe and have an excellent effect of preventing telangiectasia or improving skin redness. rice field.
本発明におけるエンドセリンＢ受容体は、血管拡張因子であるエンドセリンと結合することで、毛細血管の拡張を引き起こす。別名でエンドセリン受容体Ｂ型、エンドセリン受容体Ｂ、ｅｎｄｏｔｈｅｌｉｎ ｒｅｃｅｐｔｏｒ ｔｙｐｅ Ｂ、ｅｎｄｏｔｈｅｌｉｎ Ｂ ｒｅｃｅｐｔｏｒ、ＥＤＮＲＢ、ＥＴＢ、ＥＴ−Ｂ、ＥＴＢ１、ＥＴＢＲ、ＥＴＲＢ、ＨＳＣＲ、ＷＳ４Ａ、ＡＢＣＤＳ、ＥＴ−ＢＲ、ＨＳＣＲ２とも呼ばれる。 The endothelin B receptor in the present invention causes dilation of capillaries by binding to endothelin, which is a vasodilator. Also known as endothelin receptor B type, endothelin receptor B, endothelin receptor type B, endothelin B receptor, EDNRB, ETB, ET-B, ETB1, ETBR, ETRB, HSCR, WS4A, ABCDS, ET-BR, S.
本発明における血管内皮細胞は、血管の内腔を一層に覆う細胞である。 The vascular endothelial cells in the present invention are cells that further cover the lumen of blood vessels.
本発明における肌の赤み改善は、紫外線や酸化ストレス等の敏感肌の肌トラブルにより起こるヘモグロビンを要因とする肌の赤みを改善することを示す。 The improvement of skin redness in the present invention indicates that the skin redness caused by hemoglobin caused by skin troubles of sensitive skin such as ultraviolet rays and oxidative stress is improved.
本発明に用いるルリジサは、植物で、ハーブの一種であり、原産はヨーロッパ中部の地中海沿岸である。高さは３０〜６０センチくらいになり、淡い緑色の葉や茎は白い毛で覆われていて、夏季に青色や白色の星型の花を咲かせる。別名でボリジ・瑠璃苣・ルリヂサ、ボリヂ、ルリジシャ、ルリヂシャ、ボラゴとも呼ばれる。 Borage used in the present invention is a plant, a kind of herb, and is native to the Mediterranean coast of central Europe. The height is about 30 to 60 cm, and the pale green leaves and stems are covered with white hair, and blue and white star-shaped flowers come in summer. Also known as borage, borage, borage, borage, borage, borage, and borage.
本発明におけるルリジサの抽出物には、シソ目ムラサキ科ボラゴ属のルリジサ（学名：Ｂｏｒａｇｏ ｏｆｆｉｃｉｎａｌｉｓ）が用いられ、部位としては、花、実、種子、葉、茎、根等の植物体の一部又は全草から抽出したものである。その抽出方法は特に限定されず、例えば、加熱抽出したものであっても良いし、常温抽出したものであっても良い。又、抽出には、植物体をそのまま使用しても良く、乾燥、粉砕、細切等の処理を行っても良い。 As the extract of borage in the present invention, borage (scientific name: Borago officinalis) of the genus Borage of the family Borages of Lamiales is used, and as a part, a part of a plant such as flowers, fruits, seeds, leaves, stems and roots. Or it is extracted from whole plant. The extraction method is not particularly limited, and for example, it may be heat-extracted or room-temperature extracted. Further, for the extraction, the plant body may be used as it is, or may be subjected to treatments such as drying, crushing, and shredding.
本発明に用いるクズには、マメ科クズ属のつる性の多年草のうち、例えばクズ（Ｐｕｅｒａｒｉａ ｌｏｂａｔａ、Ｐ．ｍｏｎｔａｎａ、Ｐ．ｔｈｕｎｂｅｒｇｉａｎａ）、タイワンクズ（Ｐ．ｏｍｅｉｅｎｓｉｓ、Ｐ．ｔｏｎｋｉｎｅｎｓｉｓ）、シナノクズ（Ｐ．ｔｈｏｍｓｏｎｉｉ、Ｐ．ｃｈｉｎｅｎｓｉｓ）を用いることができる。本発明に用いるクズの抽出物とは、クズの花、実、種子、葉、茎、根等の植物体の一部又は全草が用いられ、好ましくはクズの根茎の抽出物をいう。抽出には、これらの植物体をそのまま使用しても良く、乾燥、粉砕、細切等の処理を行っても良い。別名でウマノボタモチ・久須・葛根・くずね・カッコンとも呼ばれる。 Among the vine perennials of the genus Kudzu of the leguminous family, the kudzu used in the present invention includes, for example, kudzu (Pueraria lobata, P. montana, P. tunbergiana), Thai one kudzu (P. omeiensis, P. tonkinensis), and Shinano kudzu (P. tonkinensis). Somesonii, P. chinensis) can be used. The kudzu extract used in the present invention is a part or whole plant of a plant such as a kudzu flower, fruit, seed, leaf, stem, root, etc., and preferably an extract of a kudzu rhizome. For the extraction, these plants may be used as they are, or may be subjected to treatments such as drying, crushing, and shredding. Also known as Umanobotamoch, Kusu, Kakkonto, Kuzune, and Kakkon.
抽出方法は、特に限定されないが、水もしくは熱水、又は水と有機溶媒の混合溶媒を用い、撹拌又はカラム抽出する方法等により行うことができる。抽出溶媒としては、例えば、水、低級アルコール類（メタノール、エタノール、１−プロパノール、２−プロパノール、１−ブタノール、２−ブタノール等）、液状多価アルコール類（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）、ケトン類（アセトン、メチルエチルケトン等）、アセトニトリル、エステル類（酢酸エチル、酢酸ブチル等）、炭化水素類（ヘキサン、ヘプタン、流動パラフィン等）、エーテル類（エチルエーテル、テトラヒドロフラン、プロピルエーテル等）が挙げられる。好ましくは、水、低級アルコール及び液状多価アルコール等の極性溶媒が良く、特に好ましくは、水、エタノール、１，３−ブチレングリコール及びプロピレングリコールが良い。これらの溶媒は一種でも二種以上を混合して用いても良い。特に好ましい抽出溶媒としては、水、又は水−エタノール系の混合極性溶媒が挙げられる。溶媒の使用量については、特に限定はなく、例えばルリジサの全草又はクズの根茎（乾燥重量）に対し、１０倍以上、好ましくは２０倍以上であれば良いが、抽出後に濃縮を行ったり、単離したりする場合の操作の便宜上１００倍以下であることが好ましい。又、抽出温度や時間は、用いる溶媒の種類や抽出時の圧力等によって適宜選択できる。 The extraction method is not particularly limited, but can be carried out by a method of stirring or column extraction using water or hot water, or a mixed solvent of water and an organic solvent. Examples of the extraction solvent include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.) and liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol, etc.). , Glycerin, etc.), Ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether, etc.) Etc.). Polar solvents such as water, lower alcohols and liquid polyhydric alcohols are preferred, and water, ethanol, 1,3-butylene glycol and propylene glycol are particularly preferred. These solvents may be used alone or in admixture of two or more. Particularly preferable extraction solvents include water and water-ethanol mixed polar solvents. The amount of the solvent used is not particularly limited, and may be, for example, 10 times or more, preferably 20 times or more, based on the whole plant of borage or the rhizome (dry weight) of kudzu, but may be concentrated after extraction. It is preferably 100 times or less for convenience of operation in the case of isolation. The extraction temperature and time can be appropriately selected depending on the type of solvent used, the pressure at the time of extraction, and the like.
上記抽出物は、抽出した溶液のまま用いても良いが、必要に応じて、本発明の効果を奏する範囲で、濃縮（減圧濃縮、膜濃縮等による濃縮）、希釈、濾過、活性炭等による脱色、脱臭、エタノール沈殿等の処理を行ってから用いても良い。更には、抽出した溶液を濃縮乾固、噴霧乾燥、凍結乾燥等の処理を行い、乾燥物として用いても良い。 The above extract may be used as it is in the extracted solution, but if necessary, concentration (concentration by vacuum concentration, membrane concentration, etc.), dilution, filtration, decolorization with activated carbon, etc. is performed within the range in which the effect of the present invention is exhibited. , Deodorization, ethanol precipitation, etc. may be performed before use. Further, the extracted solution may be subjected to treatments such as concentrated drying, spray drying, freeze drying and the like, and used as a dried product.
本発明は、上記抽出物をそのまま使用しても良く、抽出物の効果を損なわない範囲内で、化粧品、医薬部外品、医薬品又は食品等に用いられる成分である油脂類、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、金属石鹸、ｐＨ調整剤、防腐剤、香料、保湿剤、粉体、紫外線吸収剤、増粘剤、色素、酸化防止剤、美白剤、キレート剤、賦形剤、皮膜剤、甘味料、酸味料等の成分が含有されていても良い。 In the present invention, the above-mentioned extract may be used as it is, and fats and oils, waxes, and carbonized components used in cosmetics, non-pharmaceutical products, pharmaceuticals, foods, etc., as long as the effects of the extracts are not impaired. Hydrogens, fatty acids, alcohols, esters, surfactants, metal soaps, pH regulators, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments, antioxidants, whitening agents , Chelating agents, excipients, film agents, sweeteners, acidity agents and the like may be contained.
本発明は、化粧品、医薬部外品、医薬品、食品のいずれにも用いることができ、その剤形としては、例えば、化粧水、クリーム、乳液、ゲル剤、エアゾール剤、エッセンス、パック、洗浄剤、浴用剤、ファンデーション、打粉、口紅、軟膏、パップ剤、錠菓、カプセル剤、チョコレート、ガム、飴、飲料、散剤、顆粒剤、錠剤、糖衣錠剤、シロップ剤、丸剤、懸濁剤、液剤、乳剤、坐剤、注射用溶液等が挙げられる。 The present invention can be used for any of cosmetics, non-pharmaceutical products, pharmaceuticals, and foods, and the dosage forms thereof include, for example, cosmetics, creams, emulsions, gels, aerosols, essences, packs, and cleaning agents. , Baths, foundations, dusting, lipsticks, ointments, poultices, tablets, capsules, chocolates, gums, candy, beverages, powders, granules, tablets, sugar-coated tablets, syrups, pills, suspensions, liquids , Emulsion, suppository, solution for injection and the like.
外用の場合、本発明に用いる上記抽出物の含有量は、固形物に換算して０．０００１重量％以上が好ましく、０．００１〜１０重量％がより好ましい。更に、０．０１〜５重量％が最も好ましい。０．０００１重量％未満では十分な効果は望みにくい。１０重量％を越えると、効果の増強は認められにくく不経済である。 In the case of external use, the content of the extract used in the present invention is preferably 0.0001% by weight or more, more preferably 0.001 to 10% by weight in terms of solid matter. Further, 0.01 to 5% by weight is most preferable. If it is less than 0.0001% by weight, it is difficult to expect a sufficient effect. If it exceeds 10% by weight, the enhancement of the effect is hardly recognized and it is uneconomical.
内用の場合、摂取量は年齢、体重、症状、治療効果、投与方法、処理時間等により異なる。通常、成人１人当たりの１日の摂取量としては、５ｍｇ以上が好ましく、１０ｍｇ〜５ｇがより好ましい。更に、２０ｍｇ〜２ｇが最も好ましい。 For internal use, the intake varies depending on age, body weight, symptoms, therapeutic effect, administration method, treatment time, and the like. Usually, the daily intake per adult is preferably 5 mg or more, and more preferably 10 mg to 5 g. Further, 20 mg to 2 g is most preferable.
次に本発明を詳細に説明するため、実施例として本発明に用いる抽出物の製造例、実験例及び処方例を挙げるが、本発明はこれに限定されるものではない。製造例に示す％とは重量％を、処方例に示す含有量の部とは重量部を示す。 Next, in order to explain the present invention in detail, examples of production, experiment, and formulation of the extract used in the present invention will be given as examples, but the present invention is not limited thereto. The% shown in the production example means% by weight, and the content part shown in the formulation example means a weight part.
ルリジサ又はクズの抽出物を以下のとおり製造した。製造例１〜４において抽出材料にはルリジサの全草を用い、製造例５〜８において抽出材料にはクズの根茎を用いた。 An extract of borage or kudzu was produced as follows. In Production Examples 1 to 4, borage whole plant was used as the extraction material, and in Production Examples 5 to 8, the rhizome of waste was used as the extraction material.
（製造例１）ルリジサの熱水抽出物の調製
ルリジサの乾燥物１０ｇに２００ｍＬの水を加え、９５〜１００℃で２時間抽出した。得られた抽出液を濾過し、その濾液を濃縮し、凍結乾燥してルリジサの熱水抽出物を１．４ｇ得た。
(Production Example 1) Preparation of hot water extract of borage 200 mL of water was added to 10 g of a dried borage, and the mixture was extracted at 95 to 100 ° C. for 2 hours. The obtained extract was filtered, the filtrate was concentrated, and lyophilized to obtain 1.4 g of a hot water extract of borage.
（製造例２）ルリジサの５０％エタノール抽出物の調製
ルリジサの乾燥物１０ｇを２００ｍＬの５０％エタノール水溶液に室温で７日間浸漬し抽出を行った。得られた抽出液を濾過した後、エバポレーターで濃縮乾固してルリジサの５０％エタノール抽出物を１．１ｇ得た。
(Production Example 2) Preparation of 50% Ethanol Extract of Borage 10 g of a dried borage was immersed in 200 mL of a 50% ethanol aqueous solution at room temperature for 7 days for extraction. The obtained extract was filtered and then concentrated to dryness with an evaporator to obtain 1.1 g of a 50% ethanol extract of borage.
（製造例３）ルリジサのエタノール抽出物の調製
ルリジサの乾燥物１０ｇを２００ｍＬのエタノールに室温で７日間浸漬し抽出を行った。得られた抽出液を濾過した後、エバポレーターで濃縮乾固してルリジサのエタノール抽出物を０．４ｇ得た。
(Production Example 3) Preparation of Ethanol Extract of Borage 10 g of a dried borage was immersed in 200 mL of ethanol at room temperature for 7 days for extraction. The obtained extract was filtered and then concentrated to dryness with an evaporator to obtain 0.4 g of an ethanol extract of borage.
（製造例４）ルリジサの１，３−ブチレングリコール抽出物の調製
ルリジサの乾燥物１０ｇを２００ｍＬの１，３−ブチレングリコールに室温で７日間浸漬し抽出を行った。得られた抽出液を濾過してルリジサの１，３−ブチレングリコール抽出物を１９２ｇ得た。
(Production Example 4) Preparation of 1,3-butylene glycol extract of borage 10 g of a dried product of borage was immersed in 200 mL of 1,3-butylene glycol at room temperature for 7 days for extraction. The obtained extract was filtered to obtain 192 g of borage 1,3-butylene glycol extract.
（製造例５）クズの根茎の熱水抽出物の調製
根皮を取り除いたクズの根茎の乾燥物１０ｇに１５０ｍＬの水を加え、９５〜１００℃で２時間抽出した。得られた抽出液を濾過し、その濾液を濃縮し、凍結乾燥してクズの根茎の熱水抽出物を１．２ｇ得た。
(Production Example 5) Preparation of hot water extract of kudzu rhizome 150 mL of water was added to 10 g of dried kudzu rhizome from which the root bark had been removed, and the mixture was extracted at 95 to 100 ° C. for 2 hours. The obtained extract was filtered, the filtrate was concentrated, and freeze-dried to obtain 1.2 g of a hot water extract of rhizome of waste.
（製造例６）クズの根茎の５０％エタノール抽出物の調製
根皮を取り除いたクズの根茎の乾燥物１０ｇを１５０ｍＬの５０％エタノール水溶液に室温で７日間浸漬し、１８０ｒｐｍの速度で振盪抽出を行った。得られた抽出液を濾過した後、エバポレーターで濃縮乾固してクズの根茎の５０％エタノール抽出物を２．０ｇ得た。
(Production Example 6) Preparation of 50% ethanol extract of kudzu rhizome 10 g of dried kudzu rhizome from which the root bark has been removed is immersed in 150 mL of a 50% ethanol aqueous solution for 7 days at room temperature, and shake-extracted at a rate of 180 rpm. went. The obtained extract was filtered and then concentrated to dryness with an evaporator to obtain 2.0 g of a 50% ethanol extract of the rhizome of waste.
（製造例７）クズの根茎のエタノール抽出物の調製
根皮を取り除いたクズの根茎の乾燥物１０ｇを１００ｍＬのエタノールに室温で７日間浸漬し、１８０ｒｐｍの速度で振盪抽出を行った。得られた抽出液を濾過した後、エバポレーターで濃縮乾固してクズの根茎のエタノール抽出物を０．４ｇ得た。
(Production Example 7) Preparation of ethanol extract of kudzu rhizome 10 g of dried kudzu rhizome from which the root bark was removed was immersed in 100 mL of ethanol for 7 days at room temperature, and shake-extracted at a rate of 180 rpm. The obtained extract was filtered and then concentrated to dryness with an evaporator to obtain 0.4 g of an ethanol extract of the rhizome of waste.
（製造例８）クズの根茎の１，３−ブチレングリコール抽出物の調製
根皮を取り除いたクズの根茎の乾燥物１０ｇを２００ｍＬの１，３−ブチレングリコールに室温で７日間浸漬し、１８０ｒｐｍの速度で振盪抽出を行った。得られた抽出液を濾過してクズの根茎の１，３−ブチレングリコール抽出物を１９０ｇ得た。
(Production Example 8) Preparation of 1,3-butylene glycol extract of kudzu rhizome 10 g of dried kudzu rhizome from which the root bark was removed was immersed in 200 mL of 1,3-butylene glycol at room temperature for 7 days at 180 rpm. Shaking extraction was performed at a rate. The obtained extract was filtered to obtain 190 g of 1,3-butylene glycol extract of the rhizome of waste.
（処方例１） 化粧水
処方 含有量（部）
１．ルリジサの熱水抽出物（製造例１） ２．０
２．１，３−ブチレングリコール ８．０
３．グリセリン ２．０
４．キサンタンガム ０．０２
５．クエン酸 ０．０１
６．クエン酸ナトリウム ０．１
７．エタノール ５．０
８．パラオキシ安息香酸メチル ０．１
９．ポリオキシエチレン硬化ヒマシ油（４０Ｅ．Ｏ．） ０．１
１０．香料 適量
１１．精製水にて全量を１００とする
［製造方法］成分１〜６及び１１と、成分７〜１０をそれぞれ均一に溶解し、両者を混合し濾過して製品とする。
(Prescription example 1) Toner prescription content (part)
1. 1. Borage hot water extract (Production Example 1) 2.0
2.1,3-butylene glycol 8.0
3. 3. Glycerin 2.0
4. Xanthan gum 0.02
5. Citric acid 0.01
6. Sodium citrate 0.1
7. Ethanol 5.0
8. Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40EO) 0.1
10. Appropriate amount of fragrance 11. [Manufacturing method] Ingredients 1 to 6 and 11 and components 7 to 10 are uniformly dissolved in purified water to make the total amount 100, and both are mixed and filtered to obtain a product.
（比較処方例１） 従来の化粧水
処方例１において、ルリジサの熱水抽出物を精製水に置き換えたものを、従来の化粧水とした。
(Comparative Formulation Example 1) Conventional Toner In Formulation Example 1, the hot water extract of borage was replaced with purified water, and the conventional lotion was used.
（処方例２） クリーム
処方 含有量（部）
１．クズの根茎の５０％エタノール抽出物（製造例６） １．０
２．スクワラン ５．５
３．オリーブ油 ３．０
４．ステアリン酸 ２．０
５．ミツロウ ２．０
６．ミリスチン酸オクチルドデシル ３．５
７．ポリオキシエチレンセチルエーテル（２０Ｅ．Ｏ．） ３．０
８．ベヘニルアルコール １．５
９．モノステアリン酸グリセリン ２．５
１０．香料 ０．１
１１．パラオキシ安息香酸メチル ０．２
１２．１，３−ブチレングリコール ８．５
１３．精製水にて全量を１００とする
［製造方法］成分２〜９を加熱溶解して混合し、７０℃に保ち油相とする。成分１及び１１〜１３を加熱溶解して混合し、７５℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら冷却し、４５℃で成分１０を加え、更に３０℃まで冷却して製品とする。
(Prescription example 2) Cream prescription content (part)
1. 1. 50% ethanol extract of kudzu rhizome (Production Example 6) 1.0
2. Squalene 5.5
3. 3. Olive oil 3.0
4. Stearic acid 2.0
5. Beeswax 2.0
6. Octyldodecyl myristate 3.5
7. Polyoxyethylene cetyl ether (20EO) 3.0
8. Behenyl alcohol 1.5
9. Glycerin monostearate 2.5
10. Fragrance 0.1
11. Methyl paraoxybenzoate 0.2
12.1,3-butylene glycol 8.5
13. [Manufacturing method] Ingredients 2 to 9 having a total amount of 100 in purified water are melted by heating and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 and 11 to 13 are heated and dissolved and mixed, and kept at 75 ° C. to prepare an aqueous phase. An aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring, component 10 is added at 45 ° C., and the mixture is further cooled to 30 ° C. to obtain a product.
（比較処方例２） 従来のクリーム
処方例２において、クズの根茎の５０％エタノール抽出物を精製水に置き換えたものを、従来のクリームとした。
(Comparative Formulation Example 2) Conventional Cream In Formulation Example 2, a cream obtained by replacing the 50% ethanol extract of the rhizome of kudzu with purified water was used as a conventional cream.
（処方例３） 乳液
処方 含有量（部）
１．ルリジサのエタノール抽出物（製造例３） ０．０１
２．スクワラン ５．０
３．オリーブ油 ５．０
４．ホホバ油 ５．０
５．セタノール １．５
６．モノステアリン酸グリセリン ２．０
７．ポリオキシエチレンセチルエーテル（２０Ｅ．Ｏ．） ３．０
８．ポリオキシエチレンソルビタンモノオレエート（２０Ｅ．Ｏ．） ２．０
９．香料 ０．１
１０．プロピレングリコール １．０
１１．グリセリン ２．０
１２．パラオキシ安息香酸メチル ０．２
１３．精製水にて全量を１００とする
［製造方法］成分１〜８を加熱溶解して混合し、７０℃に保ち油相とする。成分１０〜１３を加熱溶解して混合し、７５℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら冷却し、４５℃で成分９を加え、更に３０℃まで冷却して製品とする。
(Prescription example 3) Emulsion prescription content (part)
1. 1. Borage ethanol extract (Production Example 3) 0.01
2. Squalene 5.0
3. 3. Olive oil 5.0
4. Jojoba oil 5.0
5. Cetanol 1.5
6. Glycerin monostearate 2.0
7. Polyoxyethylene cetyl ether (20EO) 3.0
8. Polyoxyethylene sorbitan monooleate (20EO) 2.0
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12. Methyl paraoxybenzoate 0.2
13. [Manufacturing method] Ingredients 1 to 8 having a total amount of 100 in purified water are melted by heating and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 10 to 13 are heated and dissolved, mixed, and kept at 75 ° C. to prepare an aqueous phase. An aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring, component 9 is added at 45 ° C., and the mixture is further cooled to 30 ° C. to obtain a product.
（処方例４） ゲル剤
処方 含有量（部）
１．ルリジサの１，３−ブチレングリコール抽出物（製造例４） １．０
２．エタノール ５．０
３．パラオキシ安息香酸メチル ０．１
４．ポリオキシエチレン硬化ヒマシ油（６０Ｅ．Ｏ．） ０．１
５．香料 適量
６．１，３−ブチレングリコール ５．０
７．グリセリン ５．０
８．キサンタンガム ０．１
９．カルボキシビニルポリマー ０．２
１０．水酸化カリウム ０．２
１１．精製水にて全量を１００とする
［製造方法］成分２〜５と、成分１及び６〜１１をそれぞれ均一に溶解し、両者を混合して製品とする。
(Prescription example 4) Gel preparation Prescription content (part)
1. 1. Borage 1,3-butylene glycol extract (Production Example 4) 1.0
2. Ethanol 5.0
3. 3. Methyl paraoxybenzoate 0.1
4. Polyoxyethylene hydrogenated castor oil (60EO) 0.1
5. Appropriate amount of fragrance 6.1,3-butylene glycol 5.0
7. Glycerin 5.0
8. Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. [Manufacturing method] Ingredients 2 to 5 and components 1 and 6 to 11 having a total amount of 100 in purified water are uniformly dissolved, and the two are mixed to obtain a product.
（処方例５） パック
処方 含有量（部）
１．クズの根茎の熱水抽出物（製造例５） ５．０
２．ポリビニルアルコール １２．０
３．エタノール ５．０
４．１，３−ブチレングリコール ８．０
５．パラオキシ安息香酸メチル ０．２
６．ポリオキシエチレン硬化ヒマシ油（２０Ｅ．Ｏ．） ０．５
７．クエン酸 ０．１
８．クエン酸ナトリウム ０．３
９．香料 適量
１０．精製水にて全量を１００とする
［製造方法］成分１〜１０を均一に溶解し製品とする。
(Prescription example 5) Pack prescription content (part)
1. 1. Hot water extract of kudzu rhizome (Production Example 5) 5.0
2. Polyvinyl alcohol 12.0
3. 3. Ethanol 5.0
4.1,3-butylene glycol 8.0
5. Methyl paraoxybenzoate 0.2
6. Polyoxyethylene hydrogenated castor oil (20EO) 0.5
7. Citric acid 0.1
8. Sodium citrate 0.3
9. Appropriate amount of fragrance 10. [Manufacturing method] Ingredients 1 to 10 having a total amount of 100 are uniformly dissolved in purified water to prepare a product.
（処方例６） ファンデーション
処方 含有量（部）
１．ルリジサの５０％エタノール抽出物（製造例２） １．０
２．ステアリン酸 ２．４
３．ポリオキシエチレンソルビタンモノステアレート（２０Ｅ．Ｏ．） １．０
４．ポリオキシエチレンセチルエーテル（２０Ｅ．Ｏ．） ２．０
５．セタノール １．０
６．液状ラノリン ２．０
７．流動パラフィン ３．０
８．ミリスチン酸イソプロピル ６．５
９．カルボキシメチルセルロースナトリウム ０．１
１０．ベントナイト ０．５
１１．プロピレングリコール ４．０
１２．トリエタノールアミン １．１
１３．パラオキシ安息香酸メチル ０．２
１４．二酸化チタン ８．０
１５．タルク ４．０
１６．ベンガラ １．０
１７．黄酸化鉄 ２．０
１８．香料 適量
１９．精製水にて全量を１００とする
［製造方法］成分２〜８を加熱溶解し、８０℃に保ち油相とする。成分１９に成分９を良く膨潤させ、続いて、成分１及び１０〜１３を加えて均一に混合する。これに粉砕機で粉砕混合した成分１４〜１７を加え、ホモミキサーで撹拌し７５℃に保ち水相とする。この油相に水相をかき混ぜながら加え、乳化する。その後、冷却し、４５℃で成分１８を加え、かき混ぜながら３０℃まで冷却して製品とする。
(Prescription example 6) Foundation prescription content (part)
1. 1. 50% ethanol extract of borage (Production Example 2) 1.0
2. Stearic acid 2.4
3. 3. Polyoxyethylene sorbitan monostearate (20EO) 1.0
4. Polyoxyethylene cetyl ether (20EO) 2.0
5. Cetanol 1.0
6. Liquid lanolin 2.0
7. Liquid paraffin 3.0
8. Isopropyl myristate 6.5
9. Sodium Carboxymethyl Cellulose 0.1
10. Bentonite 0.5
11. Propylene glycol 4.0
12. Triethanolamine 1.1
13. Methyl paraoxybenzoate 0.2
14. Titanium dioxide 8.0
15. Talc 4.0
16. Bengala 1.0
17. Yellow iron oxide 2.0
18. Appropriate amount of fragrance 19. [Manufacturing method] Ingredients 2 to 8 having a total amount of 100 in purified water are dissolved by heating and kept at 80 ° C. to prepare an oil phase. Ingredient 9 is well swollen with ingredient 19, then ingredients 1 and 10-13 are added and mixed uniformly. Ingredients 14 to 17 pulverized and mixed by a pulverizer are added thereto, and the mixture is stirred with a homomixer and kept at 75 ° C. to prepare an aqueous phase. The aqueous phase is added to this oil phase while stirring to emulsify. Then, the mixture is cooled, component 18 is added at 45 ° C., and the product is cooled to 30 ° C. with stirring to obtain a product.
（処方例７） 浴用剤
処方 含有量（部）
１．クズの根茎のエタノール抽出物（製造例７） １．０
２．炭酸水素ナトリウム ５０．０
３．黄色２０２号（１） 適量
４．香料 適量
５．硫酸ナトリウムにて全量を１００とする
［製造方法］成分１〜５を均一に混合し製品とする。
(Prescription example 7) Prescription content for bath (part)
1. 1. Ethanol extract of kudzu rhizome (Production Example 7) 1.0
2. Sodium bicarbonate 50.0
3. 3. Yellow No. 202 (1) Appropriate amount 4. Appropriate amount of fragrance 5. [Manufacturing method] Ingredients 1 to 5 having a total amount of 100 with sodium sulfate are uniformly mixed to prepare a product.
（処方例８） 軟膏
処方 含有量（部）
１．クズの根茎の１，３−ブチレングリコール抽出物（製造例８） ５．０
２．ポリオキシエチレンセチルエーテル（３０Ｅ．Ｏ．） ２．０
３．モノステアリン酸グリセリン １０．０
４．流動パラフィン ５．０
５．セタノール ６．０
６．パラオキシ安息香酸メチル ０．１
７．プロピレングリコール １０．０
８．精製水にて全量を１００とする
［製造方法］成分２〜５を加熱溶解して混合し、７０℃に保ち油相とする。成分１及び６〜８を加熱溶解して混合し、７５℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら３０℃まで冷却して製品とする。
(Prescription example 8) Ointment prescription content (part)
1. 1. 1,3-butylene glycol extract of kudzu rhizome (Production Example 8) 5.0
2. Polyoxyethylene cetyl ether (30EO) 2.0
3. 3. Glycerin monostearate 10.0
4. Liquid paraffin 5.0
5. Cetanol 6.0
6. Methyl paraoxybenzoate 0.1
7. Propylene glycol 10.0
8. [Manufacturing method] Ingredients 2 to 5 having a total amount of 100 in purified water are melted by heating and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 and 6 to 8 are heated, dissolved and mixed, and kept at 75 ° C. to prepare an aqueous phase. An aqueous phase is added to the oil phase to emulsify, and the product is cooled to 30 ° C. with stirring.
（処方例９） 散剤
処方 含有量（部）
１．ルリジサの熱水抽出物（製造例１） ０．５
２．クズの根茎の熱水抽出物（製造例５） ０．５
３．乾燥コーンスターチ ３９．０
４．微結晶セルロース ６０．０
［製造方法］成分１〜４を混合し、散剤とする。
(Prescription example 9) Powder prescription content (part)
1. 1. Borage hot water extract (Production Example 1) 0.5
2. Hot water extract of kudzu rhizome (Production Example 5) 0.5
3. 3. Dried cornstarch 39.0
4. Microcrystalline Cellulose 60.0
[Manufacturing method] Ingredients 1 to 4 are mixed to prepare a powder.
（処方例１０） 錠剤
処方 含有量（部）
１．ルリジサのエタノール抽出物（製造例３） ２．５
２．クズの根茎のエタノール抽出物（製造例７） ２．５
３．乾燥コーンスターチ ２５．０
４．カルボキシメチルセルロースカルシウム ２０．０
５．微結晶セルロース ４０．０
６．ポリビニルピロリドン ７．０
７．タルク ３．０
［製造方法］成分１〜５を混合し、次いで成分６の水溶液を結合剤として加えて顆粒成型する。成型した顆粒に成分７を加えて打錠する。１錠０．５２ｇとする。
(Prescription example 10) Tablet prescription content (part)
1. 1. Borage ethanol extract (Production Example 3) 2.5
2. Ethanol extract of kudzu rhizome (Production Example 7) 2.5
3. 3. Dried cornstarch 25.0
4. Carboxymethyl Cellulose Calcium 20.0
5. Microcrystalline Cellulose 40.0
6. Polyvinylpyrrolidone 7.0
7. Talc 3.0
[Manufacturing method] Ingredients 1 to 5 are mixed, and then an aqueous solution of ingredient 6 is added as a binder to form granules. Ingredient 7 is added to the molded granules and the mixture is locked. One tablet weighs 0.52 g.
（処方例１１） 錠菓
処方 含有量（部）
１．ルリジサのエタノール抽出物（製造例３） １．０
２．クズの根茎のエタノール抽出物（製造例７） １．０
３．乾燥コーンスターチ ４９．８
４．エリスリトール ４０．０
５．クエン酸 ５．０
６．ショ糖脂肪酸エステル ３．０
７．香料 ０．１
８．精製水 ０．１
［製造方法］成分１〜５及び８を混合し、顆粒成型する。成型した顆粒に成分６及び７を加えて打錠する。１粒１．０ｇとする。
(Prescription example 11) Tablet confectionery prescription content (part)
1. 1. Borage ethanol extract (Production Example 3) 1.0
2. Ethanol extract of kudzu rhizome (Production Example 7) 1.0
3. 3. Dried cornstarch 49.8
4. Erythritol 40.0
5. Citric acid 5.0
6. Sucrose fatty acid ester 3.0
7. Fragrance 0.1
8. Purified water 0.1
[Manufacturing method] Ingredients 1 to 5 and 8 are mixed and granulated. Ingredients 6 and 7 are added to the molded granules and the mixture is locked. One grain is 1.0 g.
（処方例１２） 飲料
処方 含有量（部）
１．ルリジサの熱水抽出物（製造例１） ０．０２５
２．クズの根茎の熱水抽出物（製造例５） ０．０２５
３．ステビア ０．０５
４．リンゴ酸 ５．０
５．香料 ０．１
６．精製水 ９４．８
［製造方法］成分３及び４を少量の水に溶解する。次いで、成分１、２、５及び６を加えて混合する。
(Prescription example 12) Beverage prescription content (part)
1. 1. Borage hot water extract (Production Example 1) 0.025
2. Hot water extract of kudzu rhizome (Production Example 5) 0.025
3. 3. Stevia 0.05
4. Malic acid 5.0
5. Fragrance 0.1
6. Purified water 94.8
[Manufacturing method] Ingredients 3 and 4 are dissolved in a small amount of water. Then, ingredients 1, 2, 5 and 6 are added and mixed.
次に、本発明の効果を詳細に説明するため、実験例を挙げる。 Next, in order to explain the effect of the present invention in detail, an experimental example will be given.
実験例１ ヒト血管内皮細胞におけるエンドセリンＢ受容体タンパク質をコードする遺伝子発現に及ぼすルリジサ及びクズの抽出物の影響
エンドセリンＢ受容体ｍＲＮＡ発現量の測定を行った。ヒト血管内皮細胞（ＨＵＶＥＣ）を６ｗｅｌｌ ｐｌａｔｅに播種し、ＨｕＭｅｄｉａ−ＥＧ２（クラボウ）の培地にて、３７℃、５％ＣＯ２条件下で培養した。コンフルエントな状態になったところで、最終濃度１０μｇ／ｍＬになるようにルリジサ抽出物（製造例１）又はクズ抽出物（製造例５）を溶解させたＨｕＭｅｄｉａ−ＥＧ２に置き換えた。添加から２４時間後に総ＲＮＡの抽出を行った。細胞からの総ＲＮＡの抽出はＲＮＡｉｓｏ Ｐｌｕｓ（タカラバイオ）を用いて行い、総ＲＮＡ量は分光光度計（ＮａｎｏＤｒｏｐ）を用いて２６０ｎｍにおける吸光度により求めた。ｍＲＮＡ発現量の測定は、細胞から抽出した総ＲＮＡを基にしてリアルタイムＲＴ−ＰＣＲ法により行った。リアルタイムＲＴ−ＰＣＲ法には、Ｈｉｇｈ Ｃａｐａｃｉｔｙ ＲＮＡ−ｔｏ−ｃＤＮＡ Ｋｉｔ（Ａｐｐｌｉｅｄ Ｂｉｏｓｙｓｔｅｍｓ）及びＳＹＢＲ Ｓｅｌｅｃｔ Ｍａｓｔｅｒ Ｍｉｘ（Ａｐｐｌｉｅｄ Ｂｉｏｓｙｓｔｅｍｓ）を用いた。即ち、５００ｎｇの総ＲＮＡを逆転写反応後、ＰＣＲ反応（９５℃：１５秒間、６０℃：６０秒間、４０ｃｙｃｌｅｓ）を行った。その他の操作は定められた方法に従い、エンドセリンＢ受容体ｍＲＮＡの発現量を、内部標準であるβ―アクチンｍＲＮＡの発現量に対する割合として求めた。エンドセリンＢ受容体発現抑制率は、コントロール（試料未添加）群のエンドセリンＢ受容体ｍＲＮＡの発現量に対する試料添加群のエンドセリンＢ受容体ｍＲＮＡの発現量の比率として算出した。尚、各遺伝子の発現量の測定に使用したプライマーは次の通りである。
Experimental Example 1 Effect of extracts of rurigisa and debris on the expression of genes encoding endothelin B receptor protein in human vascular endothelial cells The expression level of endothelin B receptor mRNA was measured. Human vascular endothelial cells (HUVEC) were seeded on a 6-well plate and cultured in HuMedia-EG2 (Kurabo) medium at 37 ° C. and 5% CO 2 conditions. When it became confluent, it was replaced with HuMedia-EG2 in which the borage extract (Production Example 1) or the waste extract (Production Example 5) was dissolved so as to have a final concentration of 10 μg / mL. Total RNA was extracted 24 hours after the addition. Extraction of total RNA from cells was performed using RNAiso Plus (Takarabio), and the total amount of RNA was determined by absorbance at 260 nm using a spectrophotometer (NanoDrop). The mRNA expression level was measured by the real-time RT-PCR method based on the total RNA extracted from the cells. For the real-time RT-PCR method, High Capacity RNA-to- cDNA Kit (Applied Biosystems) and SYBR Select Master Mix (Applied Biosystems) were used. That is, after a reverse transcription reaction of 500 ng of total RNA, a PCR reaction (95 ° C: 15 seconds, 60 ° C: 60 seconds, 40 cycles) was performed. For other operations, the expression level of endothelin B receptor mRNA was determined as a ratio to the expression level of β-actin mRNA, which is an internal standard, according to a predetermined method. The endothelin B receptor expression suppression rate was calculated as the ratio of the expression level of endothelin B receptor mRNA in the sample-added group to the expression level of endothelin B receptor mRNA in the control (non-sampled) group. The primers used to measure the expression level of each gene are as follows.
エンドセリンＢ受容体用のプライマーセット
ＣＡＡＧＧＡＣＣＣＡＴＣＧＡＧＡＴＣＡＡＧ（配列番号１）
ＣＧＡＡＣＡＣＡＡＧＧＣＡＧＧＡＣＡＣＡ（配列番号２）
β−アクチン用のプライマーセット
ＣＡＣＴＣＴＴＣＣＡＧＣＣＴＴＣＣＴＴＣＣ（配列番号３）
ＧＴＧＴＴＧＧＣＧＴＡＣＡＧＧＴＣＴＴＴＧ（配列番号４）
Primer set for endothelin B receptor CAAGGACCCATCGAGATACAG (SEQ ID NO: 1)
CGAACACAAGGCAGGACACA (SEQ ID NO: 2)
Primer set for β-actin CACTTTCCAGCCTTCCTTCC (SEQ ID NO: 3)
GTGTTGGGCGTACAGGTCTTG (SEQ ID NO: 4)
その結果を表１に示す。ヒト血管内皮細胞におけるエンドセリンＢ受容体ｍＲＮＡ発現量は、ルリジサ及びクズ抽出物により減少した。尚、ルリジサの抽出物（製造例２、３及び４）、クズの抽出物（製造例６、７及び８）にも同等の効果が認められた。 The results are shown in Table 1. The expression level of endothelin B receptor mRNA in human vascular endothelial cells was decreased by borage and kudzu extract. The same effect was observed in the borage extract (Production Examples 2, 3 and 4) and the kudzu extract (Production Examples 6, 7 and 8).
実験例２ ヒト血管内皮細胞におけるＵＶＡ照射によるエンドセリンＢ受容体発現変化に及ぼすルリジサ及びクズの抽出物の影響
ヒト血管内皮細胞（ＨＵＶＥＣ）を６ｗｅｌｌ ｐｌａｔｅに播種し、ＨｕＭｅｄｉａ−ＥＧ２（クラボウ）の培地にて、３７℃、５％ＣＯ２条件下で培養した。コンフルエントな状態になったところで、ＨＵＶＥＣをＰＢＳ（−）にて洗浄した後、ＰＢＳ（−）存在下、ＵＶＡ １０Ｊ／ｃｍ２を照射した。照射後は、最終濃度１０μｇ／ｍＬになるようにルリジサ抽出物（製造例１）又はクズ抽出物（製造例５）を溶解させたＨｕＭｅｄｉａ−ＥＧ２に置き換えた。この操作を３日間繰り返し、最終照射から２４時間培養した後、総ＲＮＡの抽出を行った。細胞からの総ＲＮＡの抽出はＲＮＡｉｓｏ Ｐｌｕｓ（タカラバイオ）を用いて行い、総ＲＮＡ量は分光光度計（ＮａｎｏＤｒｏｐ）を用いて２６０ｎｍにおける吸光度により求めた。ｍＲＮＡ発現量の測定は、細胞から抽出した総ＲＮＡを基にしてリアルタイムＲＴ−ＰＣＲ法により行った。リアルタイムＲＴ−ＰＣＲ法には、Ｈｉｇｈ Ｃａｐａｃｉｔｙ ＲＮＡ−ｔｏ−ｃＤＮＡ Ｋｉｔ（Ａｐｐｌｉｅｄ Ｂｉｏｓｙｓｔｅｍｓ）及びＳＹＢＲ Ｓｅｌｅｃｔ Ｍａｓｔｅｒ Ｍｉｘ（Ａｐｐｌｉｅｄ Ｂｉｏｓｙｓｔｅｍｓ）を用いた。即ち、５００ｎｇの総ＲＮＡを逆転写反応後、ＰＣＲ反応（９５℃：１５秒間、６０℃：６０秒間、４０ｃｙｃｌｅｓ）を行った。その他の操作は定められた方法に従い、エンドセリンＢ受容体ｍＲＮＡの発現量を、内部標準であるβ―アクチンｍＲＮＡの発現量に対する割合として求めた。エンドセリンＢ受容体発現抑制率は、コントロール（試料未添加）群のエンドセリンＢ受容体ｍＲＮＡの発現量に対する試料添加群のエンドセリンＢ受容体ｍＲＮＡの発現量の比率として算出した。
Experimental Example 2 Effect of extracts of ruridisa and debris on changes in endothelin B receptor expression by UVA irradiation in human vascular endothelial cells Human vascular endothelial cells (HUVEC) were seeded on a 6-well plate and used as a medium for HuMedia-EG2 (Kurabou). The cells were cultured at 37 ° C. under 5% CO 2 conditions. When the confluent state was reached, HUVEC was washed with PBS (−) and then irradiated with UVA 10 J / cm 2 in the presence of PBS (−). After the irradiation, the borage extract (Production Example 1) or the waste extract (Production Example 5) was replaced with HuMedia-EG2 dissolved so as to have a final concentration of 10 μg / mL. This operation was repeated for 3 days, and after culturing for 24 hours after the final irradiation, total RNA was extracted. Extraction of total RNA from cells was performed using RNAiso Plus (Takarabio), and the total amount of RNA was determined by absorbance at 260 nm using a spectrophotometer (NanoDrop). The mRNA expression level was measured by the real-time RT-PCR method based on the total RNA extracted from the cells. For the real-time RT-PCR method, High Capacity RNA-to- cDNA Kit (Applied Biosystems) and SYBR Select Master Mix (Applied Biosystems) were used. That is, after a reverse transcription reaction of 500 ng of total RNA, a PCR reaction (95 ° C: 15 seconds, 60 ° C: 60 seconds, 40 cycles) was performed. For other operations, the expression level of endothelin B receptor mRNA was determined as a ratio to the expression level of β-actin mRNA, which is an internal standard, according to a predetermined method. The endothelin B receptor expression suppression rate was calculated as the ratio of the expression level of endothelin B receptor mRNA in the sample-added group to the expression level of endothelin B receptor mRNA in the control (non-sampled) group.
その結果を表２に示す。ルリジサ及びクズ抽出物にＵＶＡ照射により上昇したエンドセリンＢ受容体ｍＲＮＡ発現量を減少させる効果が認められた。尚、ルリジサの抽出物（製造例２、３及び４）、クズの抽出物（製造例６、７及び８）にも同等の効果が認められた。 The results are shown in Table 2. The borage and kudzu extracts were found to have the effect of reducing the endothelin B receptor mRNA expression level increased by UVA irradiation. The same effect was observed in the borage extract (Production Examples 2, 3 and 4) and the kudzu extract (Production Examples 6, 7 and 8).
実験例３ ヒト血管内皮細胞におけるＵＶＡ照射による血管拡張とルリジサ及びクズの抽出物の影響
ヒト血管内皮細胞（ＨＵＶＥＣ）を６０ｍｍ ｄｉｓｈに播種し、ＨｕＭｅｄｉａ−ＥＧ２（クラボウ）の培地にて、３７℃、５％ＣＯ２条件下で培養した。コンフルエントな状態になったところで、ＨＵＶＥＣをＰＢＳ（−）にて洗浄した後、ＰＢＳ（−）存在下、ＵＶＡ １０Ｊ／ｃｍ２を照射した。照射から２４時間培養した後、ＣｅｌｌＴｒａｃｋｅｒＴＭ Ｏｒａｎｇｅ ＣＭＲＡ Ｄｙｅ（Ｉｎｖｉｔｒｏｇｅｎ）を希釈したＨｕＭｅｄｉａ−ＥＧ２に置き換えた。３０分後にＰＢＳ（−）にて洗浄した後、トリプシン−ＥＤＴＡを用いて細胞を剥離し、ＴｈｉｎＣｅｒｔ ＣＥＬＬ ＣＵＬＴＵＲＥ ＩＮＳＥＲＴ ＦＯＲ ６ ＷＥＬＬ ＰＬＡＴＥＳ（Ｇｒｅｉｎｅｒ）のインサート内に、あらかじめＣｅｌｌｍａｔｒｉｘ Ｔｙｐｅ １−Ａ（新田ゼラチン）を５００ｍＬ加えコラーゲンゲルを固形化させたものの上に、１×１０５個播種した。細胞が接着した後、その上からＣｅｌｌｍａｔｒｉｘ Ｔｙｐｅ １−Ａを５００ｍＬ加えコラーゲンゲルを固形化させ、インサート内外を最終濃度１０μｇ／ｍＬになるようにルリジサ抽出物（製造例１）又はクズ抽出物（製造例５）を溶解させたＨｕＭｅｄｉａ−ＥＧ２で満たした。添加から２４時間後に、蛍光顕微鏡（キーエンス）にて観察した。
Experimental Example 3 Vasodilation of human vascular endothelial cells by UVA irradiation and effects of borage and debris extracts Human vascular endothelial cells (HUVEC) were seeded on a 60 mm dish and placed in a medium of HuMedia-EG2 (Kurabo) at 37 ° C. Cultured under 5% CO 2 conditions. When the confluent state was reached, HUVEC was washed with PBS (−) and then irradiated with UVA 10 J / cm 2 in the presence of PBS (−). After culturing for 24 hours after irradiation, CellTracker TM Orange CMRA Dye (Invitrogen) was replaced with diluted HuMedia-EG2. After washing with PBS (-) after 30 minutes, the cells were detached using trypsin-EDTA, and Cellmatlix Type 1-A (Nitta Gelatin) was previously placed in the insert of ThinCert CELL CULTURE ENCERT FOR 6 WELL PLATES (Greener). ) Was added in an amount of 500 mL, and 1 × 10 5 cells were seeded on the solidified collagen gel. After the cells adhere, 500 mL of Cellmatlix Type 1-A is added from above to solidify the collagen gel, and the borage extract (Production Example 1) or waste extract (Production Example 1) or waste extract (manufacturing example 1) or waste extract is added so that the final concentration inside and outside the insert is 10 μg / mL. Example 5) was filled with dissolved HuMedia-EG2. Twenty-four hours after the addition, the observation was carried out with a fluorescence microscope (Keyence).
ＨＵＶＥＣによる血管形成の結果を図１、外径の計測結果を表３に示す。ＵＶＡ照射により拡張するＨＵＶＥＣが形成する血管の外径が、ルリジサ及びクズ抽出物により減少したため、ルリジサ及びクズ抽出物に毛細血管拡張抑制効果が認められた。尚、ルリジサ抽出物（製造例２、３及び４）、クズ抽出物（製造例６、７及び８）にも同等の効果が認められた。 The results of angiogenesis by HUVEC are shown in FIG. 1, and the measurement results of the outer diameter are shown in Table 3. Since the outer diameter of the blood vessels formed by HUVEC dilated by UVA irradiation was reduced by the borage and debris extracts, the effect of suppressing telangiectasia was observed in the borage and debris extracts. The same effect was observed in the borage extract (Production Examples 2, 3 and 4) and the waste extract (Production Examples 6, 7 and 8).
本発明に関わる、ルリジサ又はクズの抽出物を有効成分として含有することを特徴とするエンドセリンＢ受容体発現抑制剤、毛細血管拡張抑制剤、肌の赤み改善剤は、各剤の目的に対して優れた改善効果を発揮する。従って、肌の赤みの改善を目的とする化粧品、医薬品、医薬部外品及び食品を提供することができる。 The endothelin B receptor expression inhibitor, telangiectasia inhibitor, and skin redness improving agent, which are related to the present invention and are characterized by containing an extract of borage or waste as an active ingredient, are used for the purposes of each agent. Demonstrates an excellent improvement effect. Therefore, it is possible to provide cosmetics, pharmaceuticals, quasi-drugs and foods for the purpose of improving redness of the skin.
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