JP2024031635A - Beauty method to enhance physiological effects of flavonoid using visible light - Google Patents
Beauty method to enhance physiological effects of flavonoid using visible light Download PDFInfo
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- JP2024031635A JP2024031635A JP2022135304A JP2022135304A JP2024031635A JP 2024031635 A JP2024031635 A JP 2024031635A JP 2022135304 A JP2022135304 A JP 2022135304A JP 2022135304 A JP2022135304 A JP 2022135304A JP 2024031635 A JP2024031635 A JP 2024031635A
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Images
Landscapes
- Cosmetics (AREA)
Abstract
Description
本発明は、フラボノイドを含む皮膚外用剤を適用し、可視光下におくことを含む、フラボノイドの生理作用を増強するための美容方法、紫外線を可視光へと変換する波長変換物質とフラボノイドとを含む、皮膚外用組成物、並びにケンフェロールを含む皮膚外用剤と、可視光を照射する照射器とを含む、美容キットにも関する。 The present invention relates to a cosmetic method for enhancing the physiological effects of flavonoids, which includes applying a skin external preparation containing flavonoids and exposing the skin to visible light, and a method for enhancing the physiological effects of flavonoids, which includes applying a skin preparation containing flavonoids and exposing the skin to visible light. The present invention also relates to a cosmetic kit comprising an external skin composition containing kaempferol, an external skin preparation containing kaempferol, and an irradiator that irradiates visible light.
自然光は、主に紫外線、可視光、及び赤外線に大別される。紫外線は、皮膚癌、光老化、しみ、しわ、炎症といった悪影響を皮膚に及ぼすことが知られており、健康や美容の観点からも好ましくない。紫外線からから肌を防御するための方策が数多く取られている。例えば、日焼け止め剤の使用や、日光に当たらないような屋内での活動、UVカット加工された帽子や衣類、紫外線カットフィルムの使用などが挙げられる。一方で、可視光には、細胞を活性化する効果を有することが報告されており、特定波長を有する可視光を照射する美容方法や美容機器が開発されている。一例として630nm程度の赤色光は、皮膚深部へと到達し、マクロファージの働きを向上すること、真皮細胞を活性化することなどが報告されている。より短い波長の黄色光や緑色光では、表皮細胞が活性化され、メラニン産生抑制などの作用や、角層ターンオーバーの向上などの効能が期待されている。紫外線を避けつつ、可視光の細胞作用を利用することを目的として、照射された紫外線の波長を吸収し、そしてより長い波長の光を放出する波長変換物質を利用した美容方法や化粧品の開発が進められている。 Natural light is mainly classified into ultraviolet light, visible light, and infrared light. Ultraviolet rays are known to have adverse effects on the skin, such as skin cancer, photoaging, age spots, wrinkles, and inflammation, and are undesirable from the viewpoint of health and beauty. Many measures have been taken to protect the skin from ultraviolet radiation. Examples include using sunscreen, staying indoors to avoid exposure to sunlight, using hats and clothing with UV protection, and using UV protection film. On the other hand, it has been reported that visible light has the effect of activating cells, and beauty methods and beauty devices that irradiate visible light with a specific wavelength have been developed. For example, it has been reported that red light of about 630 nm reaches deep into the skin, improves the function of macrophages, and activates dermal cells. Yellow and green light with shorter wavelengths activate epidermal cells, and are expected to have effects such as suppressing melanin production and improving stratum corneum turnover. With the aim of utilizing the cellular effects of visible light while avoiding ultraviolet rays, the development of beauty methods and cosmetics that utilize wavelength conversion substances that absorb the wavelength of irradiated ultraviolet rays and emit light with longer wavelengths has been developed. It is progressing.
本発明の課題は、可視光により、薬効が増大する成分を取得することに関する。 An object of the present invention is to obtain a component whose medicinal efficacy is increased by visible light.
本発明者らは、薬効を有する成分のうち、可視光によりその薬効が増大する成分を見出だすため、スクリーニングを行ったところ、フラボノイドの一種であるケンフェロールが可視光によりその薬効を増大可能な成分であることが見いだされた。より具体的に、ケンフェロールは、ケラチノサイトにおける酸化ストレス抵抗性の薬効を有していたところ、紫外線照射によりその薬効が相殺又は減弱されてしまうが、さらに可視光の照射により相殺又は減弱された薬効が増大し、顕在化することを見出し、本発明に至った。
そこで本願は、以下の発明を提供する。
[1] フラボノイドを含む皮膚外用剤を適用し、可視光下におくことを含む、フラボノイドの生理作用を増強するための美容方法。
[2] フラボノイドがケンフェロールである、項目1に記載の美容方法。
[3] ブラボノイドの生理作用の増強により、肌荒れ、シワ、又はしみを抑制するか、或いは美白又は抗老化をもたらす、項目1又は2に記載の美容方法。
[4] フラボノイドの生理作用が、抗酸化作用である、項目1~3のいずれか一項に記載の美容方法。
[5] 前記皮膚外用剤が、ケンフェロール含有の植物エキスを含む、項目1~4のいずれか一項に記載の美容方法。
[6] ケンフェロール含有の植物エキスが、緑茶エキス、紅茶エキス、烏龍茶エキス、甜茶エキス、そば粉エキス、ローズアップルリーフエキス、ニームリーフエキス、イチョウ葉エキス、サンナエキス、キャベツエキス、グレープフルーツエキス、ブロッコリーエキスからなる群から選ばれる、項目5に記載の美容方法。
[7] 紫外線を可視光へと変換する波長変換物質と、フラボノイドとを含む、皮膚外用組成物。
[8] フラボノイドがケンフェロールである、項目7に記載の皮膚外用組成物。
[9] 前記波長変換物質が、紫外線から可視光へ波長を変換し、可視光がフラボノイドの生理作用を増強する、項目7又は8に記載の皮膚外用組成物。
[10] 前記波長変換物質が、紫外線を、450~700nm、好ましくは450~600nm、さらに好ましくは500~550nmの波長にピーク波長を有する可視光へと変換する、項目7~9のいずれか一項に記載の皮膚外用組成物。
[11] 前記波長変換物質が、酸化亜鉛蛍光体である、項目7~10のいずれか一項に記載の皮膚外用組成物。
[12] ケンフェロールを含む皮膚外用剤と、450~700nm、好ましくは450~600nm、さらに好ましくは500~550nmの波長で、1000~10000Luxの可視光を照射する美容照射器とを含む、美容キット。
The present inventors conducted a screening to find a component that increases its medicinal efficacy when exposed to visible light, and found that kaempferol, a type of flavonoid, can increase its medicinal efficacy when exposed to visible light. It was found that it is a component. More specifically, kaempferol had a medicinal effect on oxidative stress resistance in keratinocytes, but this medicinal effect was canceled out or attenuated by UV irradiation, but the medicinal effect was further canceled out or attenuated by visible light irradiation. The present invention was based on the discovery that the increase in the number of particles increases and becomes more obvious.
Therefore, the present application provides the following invention.
[1] A cosmetic method for enhancing the physiological effects of flavonoids, which includes applying a skin external preparation containing flavonoids and exposing the skin to visible light.
[2] The beauty method according to
[3] The beauty method according to
[4] The beauty method according to any one of
[5] The cosmetic method according to any one of
[6] Kaempferol-containing plant extracts include green tea extract, black tea extract, oolong tea extract, sweet tea extract, buckwheat extract, rose apple leaf extract, neem leaf extract, ginkgo biloba extract, sanna extract, cabbage extract, grapefruit extract, and broccoli extract. The beauty method according to item 5, selected from the group consisting of.
[7] A skin external composition containing a wavelength converting substance that converts ultraviolet rays into visible light and a flavonoid.
[8] The skin external composition according to item 7, wherein the flavonoid is kaempferol.
[9] The skin external composition according to item 7 or 8, wherein the wavelength converting substance converts the wavelength from ultraviolet rays to visible light, and the visible light enhances the physiological action of the flavonoid.
[10] Any one of items 7 to 9, wherein the wavelength conversion substance converts ultraviolet rays into visible light having a peak wavelength at a wavelength of 450 to 700 nm, preferably 450 to 600 nm, and more preferably 500 to 550 nm. The composition for external use on the skin as described in section.
[11] The skin external composition according to any one of items 7 to 10, wherein the wavelength conversion substance is a zinc oxide phosphor.
[12] A beauty kit comprising a skin external preparation containing kaempferol and a beauty irradiator that irradiates visible light of 1000 to 10,000 Lux at a wavelength of 450 to 700 nm, preferably 450 to 600 nm, more preferably 500 to 550 nm. .
本発明は、フラボノイドを含む皮膚外用剤を皮膚に適用後に、可視光下におくことにより、フラボノイドの生理作用が増強される。 In the present invention, the physiological action of flavonoids is enhanced by applying a skin external preparation containing flavonoids to the skin and then exposing the skin to visible light.
本発明は、フラボノイドを含む皮膚外用剤を適用し、可視光下におくことを含む、フラボノイドの生理作用を増強するための美容方法に関する。 The present invention relates to a cosmetic method for enhancing the physiological effects of flavonoids, which includes applying a skin external preparation containing flavonoids and exposing the skin to visible light.
本発明において、フラボノイドを含む皮膚外用剤が適用された皮膚が、可視光下におかれることで、フラボノイドの生理作用が亢進する。可視光は、照射器を用いて直接照射されてもよいし、波長変換物質を介して放出された光により間接的に照射されてもよい。可視光の照射とともに、紫外線が照射されてもよい。紫外線は、皮膚に対して有害な生理作用を引き起こしうる。一例として、活性酸素種の増大や、マトリクスプロテイナーゼの活性化、DNA損傷の誘導などが挙げられる。また、紫外線は、フラボノイドの生理作用、特に抗酸化酵素の発現量の亢進作用を、減弱又は相殺する。一方、可視光下におかれることで、紫外線により減弱又は相殺されたフラボノイドの生理作用が増強され、フラボノイドの生理作用が顕在化する(図1)。可視光下におかれるとは、日常生活における電灯や太陽光への曝露であってもよいし、照射器を用いた可視光の照射であってもよい。太陽光に暴露される場合、太陽光に含まれる紫外線の影響を和らげるために、波長変換物質及び/又は紫外線吸収物質が併用されることが好ましい。本発明の美容方法は、例えば美容サロンなどで、医師以外の美容施術者により、特定の波長の可視光を照射可能な照射器を用いて行われうる。 In the present invention, the physiological effects of flavonoids are enhanced by exposing the skin to which a skin external preparation containing flavonoids has been applied under visible light. The visible light may be directly irradiated using an irradiator, or may be irradiated indirectly by light emitted through a wavelength converting substance. In addition to visible light irradiation, ultraviolet rays may be irradiated. Ultraviolet radiation can cause harmful physiological effects on the skin. Examples include increasing reactive oxygen species, activating matrix proteinases, and inducing DNA damage. Furthermore, ultraviolet rays attenuate or offset the physiological effects of flavonoids, particularly the effect of increasing the expression level of antioxidant enzymes. On the other hand, by being exposed to visible light, the physiological effects of flavonoids that have been attenuated or offset by ultraviolet light are enhanced, and the physiological effects of flavonoids become apparent (Figure 1). Being exposed to visible light may mean exposure to electric lights or sunlight in daily life, or irradiation with visible light using an irradiator. When exposed to sunlight, it is preferable to use a wavelength converting substance and/or an ultraviolet absorbing substance in order to soften the effects of ultraviolet rays contained in sunlight. The beauty method of the present invention can be performed, for example, in a beauty salon or the like by a beauty practitioner other than a doctor using an irradiator capable of emitting visible light of a specific wavelength.
本発明において照射される可視光は、特にフラボノイドの生理作用を促進する観点から、450nm~700nmにピーク波長を有する可視光が使用され、可視光のピークはさらに450~600nm、特に500~550nmに存在することが好ましい。赤色光を照射する観点では可視光のピーク範囲は600~700nmが好ましく、黄色光を照射する観点では可視光のピーク範囲は550~600nmが好ましく、緑色光を照射する観点では可視光のピーク範囲は500~550nmが好ましい。可視光の強度は、適宜選択することができるが、1000~10000Luxの間で適宜選択することができる。このような可視光の波長及び強度は、本技術分野に周知の照射器を用いることで照射することが可能である。所定のピーク範囲には単一のピークが存在することが好ましいが、2つ又は複数のピークが存在してもよい。ピークが重なることで、ピークの判別が難しくなっていてもよい。単一ピークの可視光を照射する観点から、照射器としてはLEDを用いることが好ましい。また、発光体にたいしフィルムなどを用いてピーク範囲を絞ることもできる。 The visible light irradiated in the present invention is a visible light having a peak wavelength of 450 to 700 nm, particularly from the viewpoint of promoting the physiological action of flavonoids, and the peak of the visible light is further 450 to 600 nm, particularly 500 to 550 nm. Preferably present. From the viewpoint of irradiating red light, the peak range of visible light is preferably 600 to 700 nm, from the viewpoint of irradiating yellow light, the peak range of visible light is preferably 550 to 600 nm, and from the viewpoint of irradiating green light, the peak range of visible light is preferably 600 to 700 nm. is preferably 500 to 550 nm. The intensity of visible light can be selected as appropriate, and can be appropriately selected between 1000 and 10000 Lux. Such visible light wavelengths and intensities can be applied using illuminators well known in the art. Preferably, a single peak is present in a given peak range, but two or more peaks may be present. Overlapping peaks may make it difficult to distinguish between peaks. From the viewpoint of irradiating visible light with a single peak, it is preferable to use an LED as the irradiator. Furthermore, the peak range can be narrowed down by using a film or the like for the light emitter.
本発明の皮膚外用剤は、フラボノイドを含んでいれば任意の皮膚外用剤であってもよく、フラボノイド含有エキスを含む皮膚外用剤であってもよい。皮膚外用剤に含まれるフラボノイドとしては、ケンフェロールが特に好ましい。このような皮膚外用剤は、医薬品、医薬部外品、化粧品等であってもよい。本発明の美容方法において用いる皮膚外用剤の剤型、塗布法、投与回数等は任意に決定できる。例えば、化粧水、スプレー、オイル、クリーム、乳液、ゲル、サンスクリーン剤、サンタン剤、といった形態であってもよい。本発明の美容方法における可視光照射前に、皮膚外用剤を1回又は複数回塗布し、その後すぐに、又は一定期間、例えば10分~数時間あけて、可視光を照射してもよい。可視光の照射に代えて、屋外又は点灯された屋内で活動することで、可視光を照射されてもよい。 The external skin preparation of the present invention may be any external skin preparation as long as it contains a flavonoid, or may be an external skin preparation containing a flavonoid-containing extract. As the flavonoid contained in the external skin preparation, kaempferol is particularly preferred. Such external skin preparations may be pharmaceuticals, quasi-drugs, cosmetics, and the like. The dosage form, application method, number of administrations, etc. of the skin external preparation used in the cosmetic method of the present invention can be arbitrarily determined. For example, it may be in the form of a lotion, spray, oil, cream, emulsion, gel, sunscreen, or suntan agent. Before visible light irradiation in the cosmetic method of the present invention, the skin external preparation may be applied once or multiple times, and then visible light may be irradiated immediately or after a certain period of time, for example, 10 minutes to several hours. Instead of being irradiated with visible light, visible light may be irradiated when the subject is active outdoors or indoors with lights on.
フラボノイドは、クマル酸CoAとマロニルCoAが重合して生成するカルコンから派生する化合物群のことを指す。フラボノイドは、基礎骨格としてフラバン骨格を有し、植物種に応じて様々な化合物を包含する。フラボノイドとしては、一例としてポリフェノールが知られており、その中でも特にアントシアニン、カテキン、フラバノン、フラボン、フラボノール、イソフラボノイド、ケンフェロールなどが挙げられる。フラボノイドは、抗酸化作用を有しており、免疫亢進、抗がん作用、心血管疾患の抑制・予防作用など、様々な生理作用を発揮することが知られている。フラボノイドによる生理作用は、特に抗酸化酵素の発現増強により奏される。抗酸化酵素としては、特にチオレドキシンレダクターゼ1(TXNRD1)が挙げられる。フラボノイドのなかでもケンフェロール(kempferol)は、抗酸化、抗炎症、抗微生物、抗がん、心保護、神経保護、抗糖尿病、抗骨粗鬆症、エストロゲン/抗エストロゲン作用、抗不安、鎮痛、抗アレルギー活性などの生理作用が報告されており、化粧料、食品、及び医薬品の観点で注目されている成分である。ケンフェロールは、茶、ブロッコリー、そば、イチョウ、サンナ、キャベツ、グレープフルーツ、ローズアップル、ニームなどの植物体に含まれることが知られている。 Flavonoids refer to a group of compounds derived from chalcones produced by polymerization of coumaric acid-CoA and malonyl-CoA. Flavonoids have a flavan skeleton as a basic skeleton and include various compounds depending on the plant species. As flavonoids, polyphenols are known as an example, and among them, anthocyanins, catechins, flavanones, flavones, flavonols, isoflavonoids, kaempferol, and the like are particularly mentioned. Flavonoids have antioxidant effects and are known to exert various physiological effects, such as immune enhancement, anticancer effects, and cardiovascular disease suppression and prevention effects. The physiological effects of flavonoids are particularly exerted by enhancing the expression of antioxidant enzymes. Antioxidant enzymes include in particular thioredoxin reductase 1 (TXNRD1). Among the flavonoids, kaempferol has antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, antiosteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic, and antiallergic activities. It has been reported to have physiological effects such as, and is an ingredient that is attracting attention from the viewpoint of cosmetics, foods, and medicines. Kaempferol is known to be contained in plants such as tea, broccoli, buckwheat, ginkgo biloba, sanna, cabbage, grapefruit, rose apple, and neem.
ケンフェロールが、皮膚、特に表皮細胞における生理作用としては、抗酸化作用が挙げられる。理論に限定されることを意図するものではないが、ケンフェロールによりケラチノサイト中の抗酸化酵素の発現が増大しうる。抗酸化酵素としては、チオレドキシンレダクターゼ1(TXNRD1)、スーパーオキシドジスムターゼ(SOD)、カタラーゼ、グルタチオンペルオキシダーゼ等が挙げられる。TXNRD1は、チオレドキシンを還元し、還元型チオレドキシンを生成する反応を担う。還元型チオレドキシンは、活性酸素種(ROS)との反応に関連し、抗酸化効果を発揮する。したがって、TXNRD1の発現亢進は、細胞内における抗酸化作用を亢進することができる。他の抗酸化酵素であるスーパーオキシドジスムターゼ(SOD)、カタラーゼ、及びグルタチオンペルオキシダーゼは、活性酸素種、例えばスーパーオキシドアニオン(・O2 -)、過酸化水素を除去する反応を触媒する。紫外線の照射により、TXNRD1の発現が減少する。ケンフェロールが適用された皮膚では、ケンフェロールの抗酸化酵素発現促進作用が、紫外線照射により低減又は相殺される。ケンフェロールが適用された皮膚が、可視光下に置かれることで、ケンフェロールの生理作用、すなわち抗酸化作用が亢進する(図1)。 Physiological effects of kaempferol on the skin, particularly on epidermal cells, include antioxidant effects. Without intending to be limited by theory, kaempferol may increase the expression of antioxidant enzymes in keratinocytes. Examples of antioxidant enzymes include thioredoxin reductase 1 (TXNRD1), superoxide dismutase (SOD), catalase, and glutathione peroxidase. TXNRD1 is responsible for the reaction of reducing thioredoxin and producing reduced thioredoxin. Reduced thioredoxin is associated with reactions with reactive oxygen species (ROS) and exerts antioxidant effects. Therefore, enhanced expression of TXNRD1 can enhance intracellular antioxidant effects. Other antioxidant enzymes, superoxide dismutase (SOD), catalase, and glutathione peroxidase, catalyze reactions that remove reactive oxygen species, such as superoxide anion (.O 2 − ), hydrogen peroxide. Irradiation with ultraviolet light reduces the expression of TXNRD1. On the skin to which kaempferol has been applied, the antioxidant enzyme expression promoting effect of kaempferol is reduced or offset by ultraviolet irradiation. When the skin to which kaempferol is applied is exposed to visible light, the physiological effects of kaempferol, that is, its antioxidant effects, are enhanced (Figure 1).
フラボノイドにより発揮される生理作用を発揮させるために、フラボノイドに代えて、フラボノイド、特にケンフェロールを含むエキスを含む皮膚外用剤使用してもよい。このようなエキスとしては、フラボノイド、特にケンフェロールを含む植物体から取得されたエキスが使用可能であり、一例として緑茶エキス、紅茶エキス、烏龍茶エキス、甜茶エキス、そば粉エキス、ローズアップルリーフエキス、ニームリーフエキス、イチョウ葉エキス、サンナエキス、キャベツエキス、グレープフルーツエキス、ブロッコリーエキスが使用されうる。 In order to exert the physiological effects exerted by flavonoids, a skin external preparation containing an extract containing flavonoids, particularly kaempferol, may be used instead of flavonoids. As such extracts, extracts obtained from plants containing flavonoids, particularly kaempferol, can be used; examples include green tea extract, black tea extract, oolong tea extract, sweet tea extract, buckwheat extract, rose apple leaf extract, Neem leaf extract, ginkgo biloba extract, sanna extract, cabbage extract, grapefruit extract, broccoli extract can be used.
本明細書に記載されるエキスは常法により得ることができ、例えばその起源となる植物を抽出溶媒とともに常温又は加熱して浸漬または加熱還流した後、濾過し、濃縮して得ることができる。抽出溶媒としては、通常抽出に用いられる溶媒であれば任意に用いることができ、例えば、水性溶媒、例えば水、生理食塩水、リン酸緩衝液、ホウ酸緩衝液、あるいは有機溶媒、例えばエタノール、プロピレングリコール、1,3-ブチレングリコール、グリセリン等のアルコール類、含水アルコール類、クロロホルム、ジクロルエタン、四塩化炭素、アセトン、酢酸エチル、ヘキサン等を、それぞれ単独あるいは組み合わせて用いることができる。好ましくは、溶媒として水とアルコール、例えば1,3-ブチレングリコールの混合溶媒が使用される。上記溶媒で抽出して得られた抽出物をそのまま、あるいは例えば凍結乾燥などにより濃縮したエキスを使用でき、また必要であれば吸着法、例えばイオン交換樹脂を用いて不純物を除去したものや、ポーラスポリマー(例えばアンバーライトXAD-2)のカラムにて吸着させた後、所望の溶媒で溶出し、さらに濃縮したものも使用することができる。 The extract described in this specification can be obtained by a conventional method, for example, by immersing the plant of origin with an extraction solvent at room temperature or heating, or heating and refluxing, filtering, and concentrating. As the extraction solvent, any solvent commonly used for extraction can be used, such as an aqueous solvent such as water, physiological saline, a phosphate buffer, a borate buffer, or an organic solvent such as ethanol, Alcohols such as propylene glycol, 1,3-butylene glycol, and glycerin, hydrous alcohols, chloroform, dichloroethane, carbon tetrachloride, acetone, ethyl acetate, hexane, and the like can be used alone or in combination. Preferably, a mixed solvent of water and alcohol, such as 1,3-butylene glycol, is used as the solvent. The extract obtained by extraction with the above solvent can be used as it is, or an extract concentrated by freeze-drying can be used. If necessary, an extract with impurities removed using an adsorption method, such as an ion exchange resin, or a porous extract can be used. It is also possible to use a product that is adsorbed on a column of polymer (for example, Amberlite XAD-2), eluted with a desired solvent, and further concentrated.
本発明において波長変換物質は、特定の波長の入射光を吸収し、入射光よりも長い波長の出射光を放出する物質をいう。本発明の波長変換物質が吸収する入射光は、紫外線が好ましい。紫外線は、UVA、UVB、UVC等を含んでもよい。ある実施形態では、紫外線は、200nm~400nmにピーク波長を有する光である。また、例えば太陽光といった入射光に紫外線が含まれていてもよい。あるいは、入射光が紫外線であってもよく、人工的に生成された紫外線を用いてもよい。 In the present invention, a wavelength conversion substance refers to a substance that absorbs incident light of a specific wavelength and emits output light of a longer wavelength than the incident light. The incident light absorbed by the wavelength conversion substance of the present invention is preferably ultraviolet light. Ultraviolet light may include UVA, UVB, UVC, and the like. In some embodiments, the ultraviolet light is light with a peak wavelength between 200 nm and 400 nm. Furthermore, incident light such as sunlight may include ultraviolet rays. Alternatively, the incident light may be ultraviolet light, or artificially generated ultraviolet light may be used.
波長変換物質により放出される出射光は、紫外線よりも波長が長く、好ましくは450nm~700nm、例えば500nm~700nm又は450~600nm、さらに好ましくは500~550nmにピーク波長を有する。出射光は、例えば、限定されないものの、450nm、460nm、470nm、480nm、490nm、500nm、510nm、520nm、530nm、540nm、550nm、560nm、570nm、580nm、590nm、600nm、610nm、620nm、630nm、640nm、650nm、660nm、670nm、680nm、690nm、700nm、あるいはこれらの数値の任意の範囲内に1又は複数のピークを有してもよいし、あるいは、赤色光、橙色光、緑色光、青色光等であってもよい。ある実施形態では、波長変換物質は、200nm~400nmの励起光で励起した際に発する光の主波長が450nm~700nm、例えば500nm~700nm又は450~600nm、さらに好ましくは500~550nmを示す。 The output light emitted by the wavelength conversion substance has a longer wavelength than ultraviolet light, preferably having a peak wavelength in the range of 450 nm to 700 nm, such as 500 nm to 700 nm or 450 to 600 nm, more preferably 500 to 550 nm. The emitted light is, for example, but not limited to, 450nm, 460nm, 470nm, 480nm, 490nm, 500nm, 510nm, 520nm, 530nm, 540nm, 550nm, 560nm, 570nm, 580nm, 590nm, 600nm, 610nm, 620nm, 630nm. nm, 640 nm, It may have one or more peaks at 650nm, 660nm, 670nm, 680nm, 690nm, 700nm, or any range of these values, or it may have red light, orange light, green light, blue light, etc. There may be. In one embodiment, the wavelength converting material exhibits a dominant wavelength of light emitted when excited with excitation light of 200 nm to 400 nm, such as 500 nm to 700 nm or 450 to 600 nm, more preferably 500 to 550 nm.
波長変換物質の例として、以下の成分が挙げられる:アロフィコシアニン、C-フィコシアニン、R-フィコシアニン、フィコエリスロシアニン、B-フィコエリスリン、b-フィコエリスリン、C-フィコエリスリン、R-フィコエリスリンなどのフィコビリ蛋白;ビタミンA、βカロテン、ビタミンK、ビタミンB1、ビタミンB2、ビタミンB6、ビタミンB12、葉酸、ナイアシン、リコピン、クチナシ、ベニバナ、ウコン、コチニール、シソ、赤キャベツ、フラボノイド、カロテノイド、キノイド、ポルフィリン類、アントシアニン類、ポリフェノール類などの天然由来又は合成成分;赤色401号、赤色227号、赤色504号、赤色218号、橙色205号P、黄色4号、黄色5号、緑色201号、ピラニンコンク、青色1号、塩酸2、4-ジアミノフェノキシエタノール、アリズリンパープルSS、紫色401号、黒色401号、へリンドンピンク、黄色401号、ベンチジンエローG、青色404号、赤色104号、メタアミノフェノールなどの色素;無機化合物にドープし蛍光を持たせた蛍光体、例えば、特許第6424656号に記載の非晶質シリカ粒子と、セリウムと、リン及び/又はマグネシウムとを含む青色蛍光体および特許第6361416号に記載のアルカリ土類金属硫化物とガリウム化合物との混晶物にユーロピウムを賦活した化合物を含む赤色蛍光体、国際公開第2018/004006号に記載の酸化亜鉛蛍光体、特開2018-131422号に記載の酸化亜鉛蛍光体;特開平5-117127号に記載の無機蛍光体;等が挙げられる。ある実施形態では、無機蛍光体は、ZnO:Zn、Zn1+z、ZnO1-xのように表すことができる酸化亜鉛を国際公開第2018/004006号に記載の、例えば硫化亜鉛、硫酸亜鉛等の硫化塩及び/又は硫酸塩といった硫黄含有化合物でドープした蛍光体、MgTiO3、Mg2TiO4といったチタン酸マグネシウムをマンガンでドープしたチタン酸マグネシウム蛍光体、及びCa(H2PO4)2、CaHPO4、Ca3(PO4)2といったリン酸カルシウムをセリウムでドープしたリン酸カルシウム蛍光体から選択される1種又は複数種の蛍光体である。別の例では、酸化亜鉛蛍光体は、酸化亜鉛を還元焼成することで得られ、酸素欠陥を有しており、平均組成式はZn1+zO又はZnO1-xで表されると考えられているものである。 Examples of wavelength converting substances include the following components: allophycocyanin, C-phycocyanin, R-phycocyanin, phycoerythrocyanin, B-phycoerythrin, b-phycoerythrin, C-phycoerythrin, R-phycocyanin. Phycobiliproteins such as coerythrin; vitamin A, β-carotene, vitamin K, vitamin B1, vitamin B2, vitamin B6, vitamin B12, folic acid, niacin, lycopene, gardenia, safflower, turmeric, cochineal, perilla, red cabbage, flavonoids, carotenoids Naturally derived or synthetic ingredients such as , quinoids, porphyrins, anthocyanins, polyphenols; Red No. 401, Red No. 227, Red No. 504, Red No. 218, Orange No. 205 P, Yellow No. 4, Yellow No. 5, Green 201 No., Pyranine Conch, Blue No. 1, 2,4-diaminophenoxyethanol hydrochloride, Alizurin Purple SS, Purple No. 401, Black No. 401, Herringdon Pink, Yellow No. 401, Benzidine Yellow G, Blue No. 404, Red No. 104, Pigments such as meta-aminophenol; phosphors doped with inorganic compounds to give fluorescence, for example, blue phosphors containing amorphous silica particles, cerium, phosphorus and/or magnesium as described in Patent No. 6424656 and a red phosphor containing a compound in which europium is activated in a mixed crystal of an alkaline earth metal sulfide and a gallium compound described in Patent No. 6361416; a zinc oxide phosphor described in International Publication No. 2018/004006; Examples include the zinc oxide phosphor described in JP-A No. 2018-131422; the inorganic phosphor described in JP-A-5-117127; and the like. In some embodiments, the inorganic phosphor comprises zinc oxide, which can be represented as ZnO:Zn, Zn 1+z , ZnO 1-x, as described in WO 2018/004006, e.g., zinc sulfide, zinc sulfate. phosphors doped with sulfur-containing compounds such as sulfides and/or sulfates, magnesium titanate phosphors doped with manganese, and magnesium titanate phosphors doped with manganese, such as MgTiO 3 , Mg 2 TiO 4 , and Ca(H 2 PO 4 ) 2 , CaHPO 4 , Ca 3 (PO 4 ) 2 , which are calcium phosphate phosphors doped with cerium. In another example, zinc oxide phosphor is obtained by reducing and firing zinc oxide, has oxygen defects, and is thought to have an average compositional formula of Zn 1+z O or ZnO 1-x . This is what is being done.
波長変換物質は、動物、植物、藻類等の天然物から抽出などの方法により得ても、化学的な合成といった人工的な方法により得てもよい。例えば、フィコビリ蛋白は、スピルリナ(Spirulina platensis)などの藍藻類、チノリモ(Porphyridium purpureum)などの紅藻類といった藻類を、例えば特許第4048420号、特許第4677250号、特許第3303942号等に記載の方法で抽出することにより調製してもよい。酸化亜鉛蛍光体は、例えば国際公開第2018/004006号、特開2018-131422号、特開平5-117127号に記載の方法により製造してもよい。チタン酸マグネシウム蛍光体は、特開2017-88719号に記載の方法により製造してもよい。リン酸カルシウム蛍光体は、国際公開第2018/117117号に記載の方法により製造してもよい。なかでも、変換後の波長が500~550nmである観点から、酸化亜鉛蛍光体が好ましい。 The wavelength conversion substance may be obtained by a method such as extraction from natural products such as animals, plants, and algae, or may be obtained by an artificial method such as chemical synthesis. For example, phycobiliproteins can be obtained by using algae such as blue-green algae such as Spirulina platensis and red algae such as Porphyridium purpureum by the method described in Patent No. 4048420, Patent No. 4677250, Patent No. 3303942, etc. It may also be prepared by extraction. The zinc oxide phosphor may be produced, for example, by the method described in International Publication No. 2018/004006, Japanese Patent Application Publication No. 2018-131422, and Japanese Patent Application Publication No. 5-117127. The magnesium titanate phosphor may be manufactured by the method described in JP-A-2017-88719. The calcium phosphate phosphor may be manufactured by the method described in International Publication No. 2018/117117. Among these, zinc oxide phosphors are preferred from the viewpoint that the wavelength after conversion is 500 to 550 nm.
これらの波長変換物質は、本発明の波長変換効果を損なわない限り、上で例示した成分から構成されてもよく、含まれていてもよく、単体で使用しても複数種を混合してもよい。例えば、上記フィコビリ蛋白や無機物蛍光体に他の波長変換物質、例えば、ビタミンB(ビタミンB1、ビタミンB2、ビタミンB6、ビタミンB12等)を混合し相乗的な効果を目指してもよい。しかしながら、これらの成分は例示であり本発明の波長変換効果を奏するいかなる物質も使用可能である。 These wavelength conversion substances may be composed of or contained in the components exemplified above, and may be used alone or in combination of multiple types, as long as the wavelength conversion effect of the present invention is not impaired. good. For example, a synergistic effect may be achieved by mixing other wavelength converting substances such as vitamin B (vitamin B1, vitamin B2, vitamin B6, vitamin B12, etc.) with the above-mentioned phycobiliprotein or inorganic phosphor. However, these components are just examples, and any substance that exhibits the wavelength conversion effect of the present invention can be used.
本発明の別の態様は、紫外線を可視光へと変換する波長変換物質と、フラボノイド、特にケンフェロールとを含む、皮膚外用組成物に関する。かかる皮膚外用組成物には、波長変換物質が、フラボノイドの生理作用増強剤として配合される。これにより、皮膚外用組成物を皮膚に適用し、光照射下におかれた場合に、波長変換物質が、紫外線から可視光へ波長を変換し、可視光がフラボノイドの生理作用を増強することができる。フラボノイドの生理作用を増強することにより、特に抗酸化作用を亢進し、それにより肌荒れ、シワ、シミ、たるみ、皮膚老化(特に光老化)、紅斑、日焼けなどの炎症を抑制する作用を発揮することができる。したがって、本発明の皮膚外用組成物は、抗酸化酵素発現促進剤であってもよいし、肌荒れ、シワ、シミ、たるみ、皮膚老化の抑制剤、紅斑、日焼けなどの炎症抑制剤、或いは美白又は抗老化剤であってもよい。本発明に係る皮膚外用組成物は、定期的又は不定期的に、例えば、朝、昼、夕方など1日1回~数回、外出、野外活動、マリンスポーツ、スキーなど日差しを浴びることが予想される前などにその都度、皮膚に塗布するものであってよい。 Another aspect of the invention relates to a composition for external use on the skin, comprising a wavelength converting substance that converts ultraviolet light into visible light, and a flavonoid, particularly kaempferol. In such external skin compositions, a wavelength converting substance is blended as a physiological action enhancer of flavonoids. As a result, when the skin external composition is applied to the skin and placed under light irradiation, the wavelength converting substance converts the wavelength from ultraviolet rays to visible light, and the visible light enhances the physiological effects of flavonoids. can. By enhancing the physiological effects of flavonoids, it particularly enhances the antioxidant effect, thereby exerting the effect of suppressing inflammation such as rough skin, wrinkles, spots, sagging, skin aging (particularly photoaging), erythema, and sunburn. Can be done. Therefore, the skin external composition of the present invention may be an antioxidant enzyme expression promoter, an agent for suppressing rough skin, wrinkles, spots, sagging, skin aging, an agent for suppressing inflammation such as erythema and sunburn, or an agent for whitening or It may also be an anti-aging agent. The composition for external use on the skin according to the present invention is expected to be exposed to sunlight regularly or irregularly, for example, once to several times a day, such as in the morning, afternoon, and evening, while going out, doing outdoor activities, marine sports, skiing, etc. It may be applied to the skin each time, such as before being treated.
また、本発明の皮膚外用剤又は皮膚外用組成物は、必要に応じて、例えば、賦形剤、保存剤、増粘剤、結合剤、崩壊剤、分散剤、安定化剤、ゲル化剤、酸化防止剤、界面活性剤、保存剤、油分、粉末、水、アルコール類、増粘剤、キレート剤、シリコーン類、酸化防止剤、保湿剤、香料、各種薬効成分、防腐剤、pH調整剤、中和剤等の添加剤を任意に選択し併用することができる。さらに、本発明の効果を高めるために、他の細胞賦活化剤等を併用してもよい。 In addition, the external skin preparation or skin external composition of the present invention may contain, as necessary, excipients, preservatives, thickeners, binders, disintegrants, dispersants, stabilizers, gelling agents, Antioxidants, surfactants, preservatives, oils, powders, water, alcohols, thickeners, chelating agents, silicones, antioxidants, humectants, fragrances, various medicinal ingredients, preservatives, pH adjusters, Additives such as neutralizing agents can be arbitrarily selected and used in combination. Furthermore, in order to enhance the effects of the present invention, other cell activators and the like may be used in combination.
本発明のさらなる態様では、本発明は、フラボノイド、特にケンフェロールを含む皮膚外用剤と、450~700nm、450~600nm、又は500~550nmの波長で、1000~10000Luxの可視光を照射する照射器とを含む、美容キットに関していてもよい。かかる美容キットは、購入者により使用されてもよいし、美容施術者により使用されてもよい。可視光を照射する照射器は、本技術分野に周知の照射器を用いることで照射することが可能である。所定のピーク範囲の可視光を照射する観点から、LEDを用いることが好ましい。 In a further aspect of the present invention, the present invention provides a topical skin preparation comprising a flavonoid, in particular kaempferol, and an irradiator that irradiates visible light of 1000 to 10000 Lux at a wavelength of 450 to 700 nm, 450 to 600 nm, or 500 to 550 nm. It may also relate to a beauty kit, including. Such a beauty kit may be used by a purchaser or a beauty practitioner. The irradiator that irradiates visible light can be irradiated by using an irradiator that is well known in this technical field. From the viewpoint of irradiating visible light in a predetermined peak range, it is preferable to use an LED.
次に実施例によって本発明を更に詳細に説明する。なお、本発明はこれにより限定されるものではない。 Next, the present invention will be explained in more detail with reference to Examples. Note that the present invention is not limited to this.
実験1:細胞培養
1.正常ヒト表皮角化細胞(KK-4109 クラボウ社)をHuMedia-KG2培地(KK-2150S クラボウ)を用いて培養した。
2.細胞がコンフルエントに達した後に1.5mM CaCl2を含むEpiLife培地(MEPICF500 ThermoFisher社)に培地交換し分化誘導した。
3.24時間後にケンフェロール添加群にはケンフェロール(60010 Sigma-Ardrich社)を終濃度10μMになるように添加した。
4.ケンフェロール添加24時間後、光照射に先立ち培地をHanks’Balanced Salt Solution(HBSS)に交換した。
5.紫外線(UVB)照射群には、TL20W/12RSランプ(PHILIPS)とUG11フィルター(SCHOTT社)を用いて10mJ/cm2照射した。
6.紫外線と可視光の両方を照射する群には、紫外線照射後にソーラシミュレータ(91192-1000 Newport社)とKG1およびGG420フィルター(SCHOTT社)を用いて可視光を照射した(波長400nmから800nmの積算照射量は50J/cm2)。対照群では、ケンフェロールを添加せず、また紫外線及び可視光を照射しないことを除き同条件で実験を行った。
7.光照射終了後に培地をHBSSから1.5mM CaCl2を含むEpiLife培地に交換し、さらに24時間培養した。ケンフェロール添加群にはケンフェロールを終濃度10μMになるように添加した。
Experiment 1:
2. After the cells reached confluence, the medium was replaced with EpiLife medium (MEPICF500 ThermoFisher) containing 1.5 mM CaCl 2 to induce differentiation.
3. After 24 hours, kaempferol (60010 Sigma-Ardrich) was added to the kaempferol-added group at a final concentration of 10 μM.
4. 24 hours after addition of kaempferol, the medium was replaced with Hanks' Balanced Salt Solution (HBSS) prior to light irradiation.
5. The ultraviolet (UVB) irradiation group was irradiated with 10 mJ/cm 2 using a TL20W/12RS lamp (PHILIPS) and a UG11 filter (SCHOTT).
6. For the group to be irradiated with both ultraviolet and visible light, after ultraviolet irradiation, visible light was irradiated using a solar simulator (91192-1000 Newport) and KG1 and GG420 filters (SCHOTT) (integrated irradiation from wavelength 400 nm to 800 nm). The amount is 50 J/cm 2 ). In the control group, the experiment was conducted under the same conditions except that kaempferol was not added and no ultraviolet or visible light was irradiated.
7. After completion of light irradiation, the medium was exchanged from HBSS to EpiLife medium containing 1.5mM CaCl2 , and the cells were cultured for an additional 24 hours. Kaempferol was added to the kaempferol addition group to a final concentration of 10 μM.
実験2:RT-PCR
1.実験1終了後直ちに、RNeasy Mini Kit(QIAGEN社)を製品説明書に沿って使用しRNAを抽出した。
2.各検体より抽出したRNAサンプルについて、QuantiTect SYBR Green RT-PCR Kit(204243, QIAGEN)およびライトサイクラー(Roche社)を用いて製品説明書に従ってRT-PCR反応を行ない、チオレドキシンレダクターゼ1(TXNRD1)および内部標準としてグリセルアルデヒド-3-リン酸デヒドロゲナーゼ(GAPDH)のmRNA量を定量した。実験に用いたプライマーの配列を以下に示す。
1. Immediately after the completion of
2. RNA samples extracted from each specimen were subjected to RT-PCR reaction using QuantiTect SYBR Green RT-PCR Kit (204243, QIAGEN) and Light Cycler (Roche) according to the product instructions, and thioredoxin reductase 1 (TXNRD1) and internal As a standard, the amount of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was quantified. The sequences of the primers used in the experiment are shown below.
以上、本発明の実施の形態について説明してきた。しかしながら、本発明はこれらに限定されるものではなく、化粧料、医薬品組成物等、発明の趣旨を逸脱しない範囲で適宜変更可能である。 The embodiments of the present invention have been described above. However, the present invention is not limited to these, and may be modified as appropriate to cosmetics, pharmaceutical compositions, etc. without departing from the spirit of the invention.
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