JP5294530B2 - β-endorphin production promoter - Google Patents
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- JP5294530B2 JP5294530B2 JP2004018627A JP2004018627A JP5294530B2 JP 5294530 B2 JP5294530 B2 JP 5294530B2 JP 2004018627 A JP2004018627 A JP 2004018627A JP 2004018627 A JP2004018627 A JP 2004018627A JP 5294530 B2 JP5294530 B2 JP 5294530B2
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Abstract
Description
本発明は、β−エンドルフィンの産生を促進するβ−エンドルフィン産生促進剤に関する。さらに詳しくは、ローズウォーターを含有するβ−エンドルフィン産生促進剤に関する。 The present invention relates to a β-endorphin production promoter that promotes the production of β-endorphin. More specifically, the present invention relates to a β-endorphin production promoter containing rose water.
β−エンドルフィンは、脳下垂体の副腎皮質刺激ホルモン（ＡＣＴＨ）及びメラニン細胞刺激ホルモン（ＭＳＨ）と共通の前駆体タンパク質であるプレプロオピオメラノコルチン（ＰＯＭＣ）から生合成される内因性モルヒネ様ペプチド（オピオタイドペプチド）の一種であり、鎮痛作用や抗ストレス作用を有することから脳内快楽物質として知られている。β−エンドルフィンは、脳下垂体中葉・後葉に多く含まれ、ストレスなどの侵害要因によって血中にも分泌されることが知られているが、近年の研究によって、皮膚においてもＰＯＭＣが合成され、表皮ケラチノサイトよりβ−エンドルフィンが遊離することが明らかとされている（非特許文献１，２参照）。 β-endorphin is an endogenous morphine-like peptide (opio) that is biosynthesized from preproopiomelanocortin (POMC), a precursor protein in common with pituitary adrenocorticotropic hormone (ACTH) and melanocyte stimulating hormone (MSH). It is a kind of tide peptide) and is known as a pleasure substance in the brain because it has analgesic action and anti-stress action. β-endorphin is abundantly contained in the pituitary midlobe and posterior lobe, and is known to be secreted into the blood by noxious factors such as stress, but recent research has synthesized POMC in the skin, It has been clarified that β-endorphin is released from epidermal keratinocytes (see Non-Patent Documents 1 and 2).
しかし、β−エンドルフィンの皮膚における生理的作用については、未だ不明な点も多く、詳細な検討はなされていない現状であった。そこで、本発明者らは、ストレスによって分泌されるβ−エンドルフィンが皮膚に対して何らかの有利な作用を発揮しているのではないかとの仮説のもとに種々の検討を行った。 However, the physiological action of β-endorphin on the skin is still unclear and has not been studied in detail. Therefore, the present inventors have made various studies under the hypothesis that β-endorphin secreted by stress may exert some advantageous action on the skin.
これらの検討の結果、本発明者らは、β−エンドルフィンが皮膚において細胞賦活作用と美白作用を発揮することを見出した。 As a result of these studies, the present inventors have found that β-endorphin exhibits cell activation and whitening effects in the skin.
β−エンドルフィンが皮膚において細胞賦活作用と美白作用を発揮することが明らかとなったことから、β−エンドルフィンの産生を促進することにより、細胞賦活作用や美白作用による皮膚症状の予防や改善が可能であることが示された。このため、本発明者らはβ−エンドルフィンの産生を促進する成分を見出し、種々の皮膚症状に応用することが可能なβ−エンドルフィン産生促進剤を提供することを目的に種々の検討を行った。 Since β-endorphin has been shown to exert cell activation and whitening effects in the skin, it is possible to prevent and improve skin symptoms due to cell activation and whitening by promoting the production of β-endorphin. It was shown that. For this reason, the present inventors have found a component that promotes the production of β-endorphin, and have made various studies for the purpose of providing a β-endorphin production promoter that can be applied to various skin conditions. .
したがって、本発明の目的は、β−エンドルフィンの産生を促進する成分を見出し、種々の皮膚症状に応用することが可能なβ−エンドルフィン産生促進剤を提供することにある。 Accordingly, an object of the present invention is to provide a β-endorphin production promoter capable of finding a component that promotes the production of β-endorphin and applying it to various skin conditions.
優れた効果を発揮するβ−エンドルフィン産生促進剤を見出すために、本発明者らは、天然由来の種々の成分に関して、β−エンドルフィンの産生促進作用についての検討を行った。その結果、ローズウォーターに優れたβ−エンドルフィン産生促進作用を見出し、さらに種々の検討を行い、本発明を完成するに至った。 In order to find a β-endorphin production promoter exhibiting an excellent effect, the present inventors examined the production promotion action of β-endorphin with respect to various naturally derived components. As a result, they found a β-endorphin production promoting action excellent in rose water, and further various studies were made to complete the present invention.
すなわち、本発明は、ローズウォーターを含有するβ−エンドルフィン産生促進剤に関する。 That is, the present invention relates to a β-endorphin production promoter containing rose water.
本発明によれば、優れた効果を発揮するβ−エンドルフィン産生促進剤を得ることができる。得られたβ−エンドルフィン産生促進剤は、皮膚におけるβ−エンドルフィンの産生を促進することにより、皮膚にリラックス効果を与えるとともに、ストレスに起因する種々の皮膚症状を予防あるいは改善することが可能である。特に、細胞賦活作用や美白作用に基づく皮膚症状の予防や改善を図ることができる。本発明により予防や改善が図られる皮膚症状の例としては、しわ，たるみ，しみ，くすみ，乾燥，肌荒れなどを挙げることができる。 According to the present invention, a β-endorphin production promoter that exhibits excellent effects can be obtained. The obtained β-endorphin production promoter promotes the production of β-endorphin in the skin, thereby giving a relaxing effect to the skin and preventing or improving various skin symptoms caused by stress. . In particular, it is possible to prevent or improve skin symptoms based on cell activation and whitening. Examples of skin symptoms that can be prevented or ameliorated by the present invention include wrinkles, sagging, spots, dullness, dryness, and rough skin.
本発明の原料として用いられるローズウォーターは、ローザダマセナ（Ｒｏｓａ ｄａｍａｓｃｅｎａ Ｍｉｌｌ．）又は、ローザセンティフォリア（Ｒｏｓａ Ｃｅｎｔｉｆｏｌｉａ Ｌ．）の花を蒸留して得られる芳香成分を含む水である。 Rose water used as a raw material of the present invention is water containing an aromatic component obtained by distilling Rosa damascena ( Rosa damascena Mill.) Or Rosa Centifolia ( Rosa Centifolia L.) flowers.
ローズウォーターは、優れたβ−エンドルフィン産生促進作用を有し、β−エンドルフィン産生促進剤として利用することができる。 Rose water has an excellent β-endorphin production promoting action and can be used as a β-endorphin production promoter.
ローズウォーターを有効成分とするβ−エンドルフィン産生促進剤は、単独でも使用することが出来るが、β−エンドルフィン産生促進剤として医薬品，医薬部外品，飲食品，化粧品などの種々の組成物に配合することにより、β−エンドルフィン産生促進作用を有する組成物を得ることが出来る。 Β-Endorphin production promoter containing rosewater as an active ingredient can be used alone, but it is incorporated into various compositions such as pharmaceuticals, quasi-drugs, foods and drinks, and cosmetics as β-endorphin production promoters. By doing this, a composition having a β-endorphin production promoting action can be obtained.
ローズウォーターを有効成分とするβ−エンドルフィン産生促進剤を配合する組成物の剤型は任意であるが、組成物が皮膚外用剤，洗浄剤，浴用剤などの場合には、ローションなどの可溶化系，乳液などの乳化系，カラミンローションなどの分散系，噴射剤と共に充填したエアゾール，軟膏剤，粉末，顆粒などの種々の剤型として提供することができる。また、組成物が経口用医薬品や飲食品の場合には、ドリンク剤・点滴剤などの液剤，ガム・飴のような固形剤，カプセル，粉末，顆粒，錠剤などの一般的な剤型とすることができる。 The dosage form of the composition containing β-endorphin production promoter containing rose water as an active ingredient is arbitrary, but if the composition is a skin external preparation, a cleaning agent, a bath preparation, etc., solubilization such as lotion System, emulsified system such as emulsion, dispersion system such as calamine lotion, aerosol, ointment, powder, granule filled together with propellant. In addition, when the composition is an oral drug or food and drink, it should be a general dosage form such as liquid preparations such as drinks and drops, solid preparations such as gums and candy, capsules, powders, granules and tablets. be able to.
ローズウォーターを有効成分とするβ−エンドルフィン産生促進剤を配合する組成物には、これらの他に、必要に応じて、通常医薬品，医薬部外品，皮膚化粧料，浴用剤，洗浄剤，食品などに配合される油性成分，保湿剤，粉体，色素，乳化剤，可溶化剤，洗浄剤，紫外線吸収剤，増粘剤，薬剤，香料，樹脂，アルコール類，栄養強化物質，調味料などを適宜配合することができ、さらに他のβ−エンドルフィン産生促進剤との併用も可能である。 In addition to these, a composition containing a β-endorphin production promoter containing rose water as an active ingredient is usually a pharmaceutical, a quasi-drug, a skin cosmetic, a bath preparation, a cleaning agent, a food. Oil ingredients, moisturizers, powders, pigments, emulsifiers, solubilizers, cleaning agents, UV absorbers, thickeners, drugs, fragrances, resins, alcohols, nutrient enhancement substances, seasonings, etc. It can mix | blend suitably and can also use together with another (beta) -endorphin production promoter.
ローズウォーターを有効成分とするβ−エンドルフィン産生促進剤の種々の組成物への配合量は、組成物の種類や目的等によって調整することができるが、有効性や使用性などの点から、組成物の全量に対して０．０００１〜７５重量％が好ましく、より好ましくは０．００１〜５０重量％であり、最も好ましくは０．０１〜２５重量である。 The amount of β-endorphin production promoter containing rose water as an active ingredient can be adjusted according to the type and purpose of the composition, but from the viewpoint of effectiveness and usability, the composition 0.0001-75 weight% is preferable with respect to the whole quantity of a thing, More preferably, it is 0.001-50 weight%, Most preferably, it is 0.01-25 weight%.
ローズウォーターを有効成分とするβ−エンドルフィン産生促進剤、あるいは該β−エンドルフィン産生促進剤を配合したβ−エンドルフィン産生促進用組成物は、ストレスに起因する種々の皮膚症状を予防あるいは改善することが可能である。特に、細胞賦活作用や美白作用に基づく皮膚症状の予防や改善を図ることができ、その例としては、しわ，たるみ，しみ，くすみ，乾燥，肌荒れなどの皮膚症状を挙げることができる。 A β-endorphin production promoter containing rosewater as an active ingredient, or a β-endorphin production promoter composition containing the β-endorphin production promoter, can prevent or improve various skin symptoms caused by stress. Is possible. In particular, it is possible to prevent or improve skin symptoms based on cell activation and whitening effects, and examples include skin symptoms such as wrinkles, sagging, spots, dullness, dryness, and rough skin.
以下に、抽出物の製造例、作用を評価するための試験について詳細に説明するが、本発明の技術的範囲はこれによってなんら限定されるものではない。 Hereinafter, the production example of the extract and the test for evaluating the action will be described in detail, but the technical scope of the present invention is not limited thereto.
［製造例１］ ローズウォーターの調製
早朝の開花直前のローザセンティフォリア（Ｒｏｓａ Ｃｅｎｔｉｆｏｌｉａ Ｌ．）の花１ｋｇを水蒸気蒸留法により香料成分と水溶性成分に分離し、このうちの水溶性成分を分取後、濾過を行い、ローズウォーターを得た。
[Production Example 1] Preparation of Rose Water 1 kg of Rosacentifolia ( Rosa Centifolia L.) flowers just before flowering in the early morning are separated into a fragrance component and a water-soluble component by a steam distillation method, and the water-soluble component is fractionated. Thereafter, filtration was performed to obtain rose water.
［β−エンドルフィン産生促進作用の評価］
試料には、製造例１にて調製したローズウォーターを用いた。評価は、以下の手順で行った。ヒト表皮細胞を１ウェル当たり２．０×１０４個となるように９６穴マイクロプレートに播種した。播種培地には、市販のダルベッコ改変イーグル培地（ＤＭＥＭ）に５％のウシ胎児血清を添加したものを用いた。２４時間培養後、任意の濃度の試料を添加した試験培地に交換し、さらに４８時間培養した。培養後に培養上清中に分泌されたβ−エンドルフィン産生量をＥＬＩＳＡ法により定量した。また、同時に細胞数を計測し、細胞当たりのβ−エンドルフィン産生量を算出した。各試料の評価結果を、ブランクの細胞当りのβ−エンドルフィン産生量を１００とした場合の相対値にて表１に示す。なお、表中の**は、ｔ検定における有意確率Ｐ値に対し、有意確率１％未満の危険率（Ｐ＜０．０１）で有意差が認められたものを表したものである。
[Evaluation of β-endorphin production promoting effect]
As the sample, the rose water prepared in Production Example 1 was used. The evaluation was performed according to the following procedure. Human epidermal cells were seeded in a 96-well microplate so as to be 2.0 × 10 4 cells per well. As the seeding medium, a commercially available Dulbecco's modified Eagle medium (DMEM) with 5% fetal bovine serum added was used. After culturing for 24 hours, the culture medium was replaced with a test medium to which a sample having an arbitrary concentration was added, and further cultured for 48 hours. The amount of β-endorphin produced secreted into the culture supernatant after culturing was quantified by ELISA. At the same time, the number of cells was counted, and the amount of β-endorphin produced per cell was calculated. The evaluation results of each sample are shown in Table 1 as relative values when the amount of β-endorphin production per blank cell is 100. In addition, ** in the table indicates that a significant difference was recognized with a risk rate (P <0.01) having a significance probability of less than 1% with respect to the significance probability P value in the t-test.
表１より、試料を添加した培地において、有意なβ−エンドルフィン産生促進作用が認められた。特に、試料を１．２５〜２．５％培地に添加した場合には、ブランクと比較して、危険率５％未満で、また試料を５．０％培地に添加した場合には、危険率１％未満で有意なβ−エンドルフィン産生促進作用が認められた。このことから、ローズウォーターは、優れたβ−エンドルフィン産生促進作用を有することが明らかとなった。 From Table 1, a significant β-endorphin production promoting action was observed in the medium to which the sample was added. In particular, when the sample is added to the 1.25-2.5% medium, the risk is less than 5% compared to the blank, and when the sample is added to the 5.0% medium, the risk is A significant β-endorphin production promoting effect was observed at less than 1%. From this, it became clear that rose water has an excellent β-endorphin production promoting action.
上記の検討により、ローズウォーターは、β−エンドルフィン産生促進剤として優れていることが明らかとなり、このβ−エンドルフィン産生促進作用により、β−エンドルフィンの有する細胞賦活作用や美白作用を増強し、しわ，たるみ，しみ，くすみ，乾燥，肌荒れなど皮膚症状の予防や改善が可能であることが明らかとなった。 From the above examination, it became clear that rose water is excellent as a β-endorphin production promoter, and this β-endorphin production promotion action enhances the cell activation action and whitening action of β-endorphin, wrinkles, It was revealed that skin symptoms such as sagging, spots, dullness, dryness, and rough skin can be prevented or improved.
最後に、ローズウォーターを有効成分とするβ−エンドルフィン産生促進剤を含有する組成物の処方例として、皮膚外用剤及び食品の処方例を示すが、本発明のβ−エンドルフィン産生促進剤を配合する組成物は、これらに限定されるものではない。なお、各処方例に配合したβ−エンドルフィン産生促進剤には、製造例１にて製造したローズウォーターを用いた。 Finally, as a formulation example of a composition containing a β-endorphin production promoter containing rosewater as an active ingredient, a skin external preparation and a food formulation example will be shown, but the β-endorphin production promoter of the present invention is blended. The composition is not limited to these. In addition, the rose water manufactured by manufacture example 1 was used for the beta-endorphin production promoter mix | blended with each prescription example.
［処方例１］ローション
（１）エタノール ５．０（重量％）
（２）パラオキシ安息香酸メチル ０．１
（３）フェノキシエタノール ０．０５
（４）ポリオキシエチレン（４０Ｅ．Ｏ．）硬化ヒマシ油 ０．３
（５）香料 ０．１
（６）β−エンドルフィン産生促進剤 ５．０
（７）精製水 １００とする残余
（８）クエン酸 ０．０２
（９）クエン酸ナトリウム ０．１
（10）ヒドロキシエチルセルロース ０．１５
製法：（１）に（２）〜（５）を溶解する。溶解後、（６）〜（９）を順次添加した後、十分に攪拌し、（10）を加え、均一に混合し、ローションを得た。
[Prescription Example 1] Lotion (1) Ethanol 5.0 (% by weight)
(2) Methyl paraoxybenzoate 0.1
(3) Phenoxyethanol 0.05
(4) Polyoxyethylene (40E.O.) hydrogenated castor oil 0.3
(5) Fragrance 0.1
(6) β-endorphin production promoter 5.0
(7) Residue as 100 (8) Citric acid 0.02
(9) Sodium citrate 0.1
(10) Hydroxyethyl cellulose 0.15
Production method: (2) to (5) are dissolved in (1). After dissolution, (6) to (9) were sequentially added, and then sufficiently stirred, (10) was added and mixed uniformly to obtain a lotion.
［処方例２］水性ジェル
（１）カルボキシビニルポリマー（１重量％水溶液） １７．５(重量％)
（２）アルギン酸ナトリウム(１重量％水溶液) １５．０
（３）β−エンドルフィン産生促進剤 １５．０
（４）ショ糖脂肪酸エステル １．３
（５）エタノール １０．０
（６）モノラウリン酸ポリグリセリル １．０
（７）精製水 １００とする残余
（８）スクワラン ２．０
（９）ベヘニルアルコール ０．７５
（10）ホホバ油 １．０
（11）Ｌ−アルギニン（１０重量％水溶液） ２．０
（12）香料 ０．１
製法：（１）〜（７）の水相成分を混合し、７５℃にて加熱溶解する。一方、（８）〜（10）の油相成分を混合し、７５℃にて加熱溶解する。次いで、上記水相成分に油相成分を添加して予備乳化を行った後、ホモミキサーにて均一に乳化する。乳化終了後に冷却を開始し、５０℃にて（11）を加える。さらに４０℃まで冷却し、（12）を加え、均一に混合し、水性ジェルを得た。
[Formulation Example 2] Aqueous gel (1) Carboxyvinyl polymer (1 wt% aqueous solution) 17.5 (wt%)
(2) Sodium alginate (1 wt% aqueous solution) 15.0
(3) β-endorphin production promoter 15.0
(4) Sucrose fatty acid ester 1.3
(5) Ethanol 10.0
(6) Polyglyceryl monolaurate 1.0
(7) Residual remaining 100 (8) Squalane 2.0
(9) Behenyl alcohol 0.75
(10) Jojoba oil 1.0
(11) L-arginine (10% by weight aqueous solution) 2.0
(12) Fragrance 0.1
Production method: The aqueous phase components (1) to (7) are mixed and dissolved by heating at 75 ° C. On the other hand, the oil phase components (8) to (10) are mixed and dissolved by heating at 75 ° C. Next, the oil phase component is added to the aqueous phase component and preliminary emulsification is performed, followed by uniform emulsification with a homomixer. Cooling is started after completion of emulsification, and (11) is added at 50 ° C. Furthermore, it cooled to 40 degreeC, (12) was added, and it mixed uniformly, and obtained the aqueous gel.
［処方例３］クリーム
（１）スクワラン １０．０（重量％）
（２）ステアリン酸 ２．０
（３）水素添加パーム核油 ０．５
（４）水素添加大豆リン脂質 ０．１
（５）セタノール ３．６
（６）親油型モノステアリン酸グリセリン ２．０
（７）グリセリン １０．０
（８）パラオキシ安息香酸メチル ０．１
（９）アルギニン（２０重量％水溶液） １５．０
（10）精製水 １００とする残余
（11）カルボキシビニルポリマー（１重量％水溶液） １５．０
（12）β−エンドルフィン産生促進剤 １．０
製法：（１）〜（６）の油相成分を８０℃にて加熱溶解する。一方（７）〜（10）の水相成分を８０℃にて加熱溶解する。これに前記油相成分を攪拌しながら加え、ホモジナイザーにより均一に乳化する。乳化終了後、（11）を加え、冷却を開始し、４０℃にて（12）を加え、均一に混合する。
[Prescription Example 3] Cream (1) Squalane 10.0 (% by weight)
(2) Stearic acid 2.0
(3) Hydrogenated palm kernel oil 0.5
(4) Hydrogenated soybean phospholipid 0.1
(5) Cetanol 3.6
(6) Lipophilic glyceryl monostearate 2.0
(7) Glycerin 10.0
(8) Methyl paraoxybenzoate 0.1
(9) Arginine (20% by weight aqueous solution) 15.0
(10) Purified water 100 (11) Carboxyvinyl polymer (1 wt% aqueous solution) 15.0
(12) β-endorphin production promoter 1.0
Production method: The oil phase components (1) to (6) are heated and dissolved at 80 ° C. On the other hand, the aqueous phase components (7) to (10) are dissolved by heating at 80 ° C. The oil phase component is added to this while stirring and uniformly emulsified with a homogenizer. After the emulsification is completed, add (11), start cooling, add (12) at 40 ° C., and mix uniformly.
［処方例４］内服液
（１）β−エンドルフィン産生促進剤 ３．０(重量％)
（２）クエン酸 ０．１
（３）ステビア ０．０１
（４）精製水 ９３．８９
（５）エリスリトール ３．０
製法：（１）〜（５）を均一に混合する。
[Prescription Example 4] Internal liquid (1) β-endorphin production promoter 3.0 (% by weight)
(2) Citric acid 0.1
(3) Stevia 0.01
(4) Purified water 93.89
(5) Erythritol 3.0
Production method: (1) to (5) are mixed uniformly.
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