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JP6803110B2 - External and internal skin preparations containing an extract of nasturtium cultivated by irradiating light with a specific wavelength range - Google Patents

External and internal skin preparations containing an extract of nasturtium cultivated by irradiating light with a specific wavelength range Download PDF

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JP6803110B2
JP6803110B2 JP2015066328A JP2015066328A JP6803110B2 JP 6803110 B2 JP6803110 B2 JP 6803110B2 JP 2015066328 A JP2015066328 A JP 2015066328A JP 2015066328 A JP2015066328 A JP 2015066328A JP 6803110 B2 JP6803110 B2 JP 6803110B2
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恭子 出口
恭子 出口
大隅 和寿
和寿 大隅
曜 田中
曜 田中
坂井田 勉
勉 坂井田
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Nippon Menard Cosmetic Co Ltd
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本発明は、抗酸化効果、マトリックスメタロプロテアーゼ(MMP)阻害効果、美白効果などに優れた新規な皮膚外用剤又は内用剤に関する。 The present invention relates to a novel external or internal skin preparation having excellent antioxidant effect, matrix metalloproteinase (MMP) inhibitory effect, whitening effect and the like.

皮膚は生体の最外層に位置し、紫外線等の影響により活性酸素が発生しやすい臓器であり、絶えずその酸素ストレスに曝されている。一方、皮膚細胞内には活性酸素消去酵素が存在しており、その能力を超える活性酸素が発生しないかぎり活性酸素の傷害から皮膚細胞を防衛している。ところが、皮膚細胞内の活性酸素消去酵素の活性は加齢とともに低下することが知られており、活性酸素による傷害がその防御反応を凌駕したとき、皮膚は酸化され、細胞機能が劣化して老化してゆくと考えられる。また、皮膚以外の臓器においても、その活性酸素消去能を越える活性酸素に曝されたとき、機能低下が起こり老化したり、ガンや心筋梗塞など様々な生活習慣病が発症すると考えられる。そこで、活性酸素による傷害からの防御を目的として活性酸素消去剤や抗酸化剤が検討され、SODやカタラーゼ等の活性酸素消去酵素、SOD様活性物質などの活性酸素消去剤や抗酸化剤を配合した食品、化粧品、医薬部外品及び医薬品等が開発されている(特許文献1,2参照)。 The skin is located in the outermost layer of the living body, and is an organ that easily generates active oxygen due to the influence of ultraviolet rays and the like, and is constantly exposed to the oxygen stress. On the other hand, active oxygen scavenging enzyme exists in the skin cell and protects the skin cell from the damage of the active oxygen unless the active oxygen exceeding its capacity is generated. However, it is known that the activity of active oxygen scavenging enzyme in skin cells decreases with aging, and when the damage caused by active oxygen exceeds the defense reaction, the skin is oxidized, the cell function deteriorates and aging. It is thought that it will continue. In addition, it is considered that when an organ other than the skin is exposed to active oxygen exceeding its active oxygen scavenging ability, functional deterioration occurs and aging occurs, and various lifestyle-related diseases such as cancer and myocardial infarction develop. Therefore, active oxygen scavengers and antioxidants have been studied for the purpose of protection from damage caused by active oxygen, and active oxygen scavengers such as SOD and catalase, and active oxygen scavengers and antioxidants such as SOD-like active substances are blended. Foods, cosmetics, non-pharmaceutical products, pharmaceuticals, etc. have been developed (see Patent Documents 1 and 2).

皮膚は、紫外線、乾燥、寒冷、熱、薬物等の様々な物理的及び化学的ストレスに日々曝されている。その結果、皮膚の機能低下が引き起こされ、様々な皮膚の老化現象が顕在化する。皮膚の老化現象の一つに、しわがある。しわには、表皮性のしわと、真皮性のしわの二種類が存在することが知られている。表皮性のしわは小じわと呼ばれ、皮膚の乾燥により、表皮角質層中の水分量が低下することによって一時的に生じるしわである。小じわの改善方法としては、保湿効果を有する化粧品の使用が一般的である。一方、真皮性のしわは、太陽光線に含まれる紫外線や加齢によって形成されるしわである。その形成メカニズムとしては、紫外線や加齢による真皮線維芽細胞におけるマトリックスメタロプロテアーゼ(MMP)の増加によるコラーゲンの分解促進が挙げられる。 The skin is exposed daily to various physical and chemical stresses such as UV, dry, cold, heat and drugs. As a result, skin dysfunction is caused, and various skin aging phenomena become apparent. Wrinkles are one of the skin aging phenomena. It is known that there are two types of wrinkles: epidermal wrinkles and dermal wrinkles. Epidermal wrinkles are called fine wrinkles, which are temporary wrinkles caused by a decrease in the amount of water in the stratum corneum of the epidermis due to dry skin. As a method for improving fine wrinkles, it is common to use cosmetics having a moisturizing effect. On the other hand, dermal wrinkles are wrinkles formed by ultraviolet rays contained in sunlight and aging. The formation mechanism includes promotion of collagen degradation by an increase in matrix metalloproteinase (MMP) in dermal fibroblasts due to ultraviolet rays and aging.

乾燥に起因する表皮性のしわと真皮性のしわでは、組織学的形態、発症メカニズム、治療方法が異なり、紫外線や加齢により生じる真皮性のしわは、保湿効果を有する化粧品の使用によっては改善できない。 Epidermal wrinkles caused by dryness and dermal wrinkles have different histological morphology, onset mechanism, and treatment method, and dermal wrinkles caused by ultraviolet rays and aging can be improved by using cosmetics having a moisturizing effect. Can not.

これまでに、紫外線によって生じる真皮性のしわを改善することを目的として、加水分解アーモンドを有効成分とする皮膚のしわ形成防止・改善剤(特許文献3)、ジョチョウケイ、テンキシ及びキセンウの抽出物を有効成分とする紫外線照射に起因するしわの改善剤(特許文献4)が報告されている。 So far, for the purpose of improving dermal wrinkles caused by ultraviolet rays, an agent for preventing / improving skin wrinkles containing hydrolyzed almond as an active ingredient (Patent Document 3), extracts of Jochokei, Tenxi and Kisenu An agent for improving wrinkles caused by irradiation with ultraviolet rays containing the active ingredient (Patent Document 4) has been reported.

コラーゲンは、哺乳動物組織の約1/3を占める主要な構造タンパク質であり、軟骨、骨、腱、及び皮膚を含む多くのマトリックス組織の必須な成分である。マトリックスメタロプロテアーゼ(MMP)に属するコラゲナーゼ(MMP−1)により1箇所を切断されると、通常の組織内では安定なコラーゲン分子は、変性して一本鎖のゼラチンとなり、他の様々なプロテアーゼにより分解されるようになる。その結果、マトリックス組織の構造の完全性が失われてしまう。 Collagen is a major structural protein that makes up about one-third of mammalian tissue and is an essential component of many matrix tissues, including cartilage, bone, tendons, and skin. When one site is cleaved by collagenase (MMP-1), which belongs to matrix metalloproteinase (MMP), collagen molecules that are stable in normal tissues are denatured into single-stranded gelatin by various other proteases. It will be disassembled. As a result, the structural integrity of the matrix structure is lost.

MMPに属するゼラチナーゼ(MMP−2など)は、線維芽細胞や内皮細胞、ガン細胞等が産生する酵素であり、コラーゲン、ゼラチン、エラスチン(動脈、腱、皮膚など弾性組織の特殊成分をなす構造タンパク質)等の基質や基底膜の主要構成成分であるラミニン5などを分解する。その発現及び活性は、紫外線の照射により大きく増加し、紫外線による基底膜成分の減少、基底膜の構造変化の原因となり、皮膚におけるシワやたるみの形成等の大きな要因となることが明らかとなっている(非特許文献1参照)。従って、ゼラチナーゼに対して阻害活性を有する物質は、皮膚におけるシワやたるみの予防だけでなく、ガン組織における血管新生やガンの転移を抑制する効果が期待され、ガン疾患の予防、治療に有用であると考えられる。さらに、MMPは、潰瘍形成、慢性関節リュウマチ、骨粗鬆症、歯周炎等の種々の病態での細胞外基質の分解に関与していることが報告されている。よって、MMPの阻害活性を有すれば、ガンの転移、潰瘍形成、慢性関節リュウマチ、骨粗鬆症、歯周炎等、MMPの亢進が原因で起こる各種疾患の治療及び改善に有用である。 Gelatinase (MMP-2, etc.) belonging to MMP is an enzyme produced by fibroblasts, endothelial cells, cancer cells, etc., and is a structural protein that forms a special component of elastic tissues such as collagen, gelatin, and elastin (arteries, tendons, skin, etc.). ) Etc. and laminin 5 which is a main constituent of the basement membrane are decomposed. It has been clarified that its expression and activity are greatly increased by irradiation with ultraviolet rays, cause a decrease in basement membrane components due to ultraviolet rays, cause structural changes in the basement membrane, and become a major factor such as formation of wrinkles and sagging in the skin. (See Non-Patent Document 1). Therefore, a substance having an inhibitory activity against zelatinase is expected to have an effect of suppressing angiogenesis and cancer metastasis in cancer tissues as well as preventing wrinkles and sagging in the skin, and is useful for prevention and treatment of cancer diseases. It is believed that there is. Furthermore, MMP has been reported to be involved in the degradation of extracellular matrix in various pathological conditions such as ulceration, rheumatoid arthritis, osteoporosis, and periodontitis. Therefore, if it has an inhibitory activity on MMP, it is useful for treating and ameliorating various diseases caused by an increase in MMP, such as cancer metastasis, ulceration, rheumatoid arthritis, osteoporosis, and periodontitis.

一般に、シミ、ソバカス、日焼け等に見られる皮膚の色素沈着は、ホルモンの異常や紫外線の刺激により、皮膚内に存在するメラノサイトがメラニン色素を過剰に生成し、これが皮膚内に沈着することが原因と考えられている。このような色素沈着を防ぐ方法の一つに、メラニンの過剰な生成を抑制する方法が知られている。従来、色素沈着の治療には、内用や外用などにおいて、アスコルビン酸(ビタミンC)等が用いられてきた。 In general, skin pigmentation seen in age spots, freckles, sunburn, etc. is caused by excessive production of melanin pigment by melanocytes existing in the skin due to abnormal hormones or stimulation of ultraviolet rays, which is deposited in the skin. It is believed that. As one of the methods for preventing such pigmentation, a method for suppressing excessive production of melanin is known. Conventionally, ascorbic acid (vitamin C) and the like have been used for the treatment of pigmentation for internal and external use.

ナスタチウムの公知文献としては、活性酸素消去、ヒアルロン酸合成促進・分解抑制やアクアポリン合成促進効果(特許文献5)などが知られていた。 Known documents for nasturtium include scavenging active oxygen, promoting / decomposing hyaluronic acid synthesis, and promoting aquaporin synthesis (Patent Document 5).

一方で、植物の栽培方法によって植物の薬効を高める方法として、植物体内のビタミンやポリフェノール、ルチンなどの機能性物質を特徴的に増加させる方法は、すでに特許文献で報告されている。特許文献6には、大豆もやしに近紫外〜青色領域波長の光を照射することにより、含有ビタミンA、ビタミンEを増量させる方法が開示されており、特許文献7には、小松菜に対して、人工紫外線照射を1日5分間行うことで、機能性物質であるα−トコフェロールやビタミンCを増加させる栽培方法が開示され、特許文献8には、人工光源の青色光、赤色光及び遠赤色光の強度を調整することにより、小松菜、レタスのビタミンCやビタミンAを増加させる方法が開示されている。 On the other hand, as a method for enhancing the medicinal effect of a plant by a plant cultivation method, a method for characteristically increasing functional substances such as vitamins, polyphenols and rutin in the plant has already been reported in patent documents. Patent Document 6 discloses a method for increasing the amount of vitamin A and vitamin E contained in soybean sprouts by irradiating the soybean sprouts with light having a wavelength in the near-ultraviolet to blue region. A cultivation method for increasing α-tocopherol and vitamin C, which are functional substances, by performing artificial ultraviolet irradiation for 5 minutes a day is disclosed, and Patent Document 8 discloses blue light, red light, and far-red light of artificial light sources. A method of increasing vitamin C and vitamin A of Japanese mustard spinach and lettuce by adjusting the intensity of the Japanese mustard spinach is disclosed.

特開平9−118630号公報Japanese Unexamined Patent Publication No. 9-118630 特開平9−208484号公報Japanese Unexamined Patent Publication No. 9-208484 特開2000−119125号公報Japanese Unexamined Patent Publication No. 2000-119125 特開2006−199611号公報Japanese Unexamined Patent Publication No. 2006-199611 特開2004−168732号公報Japanese Unexamined Patent Publication No. 2004-168732 特開平11−103680号公報Japanese Unexamined Patent Publication No. 11-103680 特開2004−305040号公報Japanese Unexamined Patent Publication No. 2004-305040 特開平8−205677号公報Japanese Unexamined Patent Publication No. 8-205677

Gary J.Fisher et al., Nature, Vol.379, No.25, pp335, 1996Gary J. Fisher et al. , Nature, Vol. 379, No. 25, pp335, 1996

本発明は、抗酸化効果、マトリックスメタロプロテアーゼ(MMP)阻害効果、美白効果などに優れた新規な皮膚外用剤又は内用剤を提供することを課題とする。 An object of the present invention is to provide a novel external or internal skin preparation having excellent antioxidant effect, matrix metalloproteinase (MMP) inhibitory effect, whitening effect and the like.

本発明者らは、この問題点を解決すべく、鋭意研究を重ねた結果、特定の波長域を有する2種の光を同時に照射して栽培したナスタチウムの抽出物に、抗酸化効果、マトリックスメタロプロテアーゼ(MMP)阻害効果及び美白効果が優れていることを発見し、本発明を完成するに至った。 As a result of intensive research to solve this problem, the present inventors have applied an antioxidant effect and matrix metalloproteinase to an extract of nastatium cultivated by simultaneously irradiating two kinds of light having a specific wavelength range. We have discovered that the protease (MMP) inhibitory effect and the whitening effect are excellent, and have completed the present invention.

すなわち、本発明は、以下の(1)〜(7)からなる。 That is, the present invention comprises the following (1) to (7).

(1)波長域570〜730nmと400〜515nmとの光合成光量子束密度(PPFD)比が8:1〜1:1の光を照射して栽培したナスタチウムの、水、低級アルコール及び液状多価アルコールから選ばれる一種又は二種以上の溶媒による抽出物を含有することを特徴とする皮膚外用剤。
(2)波長域570〜730nmと400〜515nmとの光合成光量子束密度(PPFD)比が、4:1〜2:1であることを特徴とする請求項1記載の皮膚外用剤。
(3)波長域570〜730nmと400〜515nmとの光合成光量子束密度(PPFD)比が8:1〜1:1の光を照射して栽培することによって、蛍光灯又は太陽光で栽培したナスタチウムと比較して、抗酸化効果、マトリックスメタロプロテアーゼ(MMP)阻害効果及び美白効果から選ばれる一種又は二種以上の効果を高めることを特徴とするナスタチウム。
(4)波長域570〜730nmと400〜515nmとの光合成光量子束密度(PPFD)比が8:1〜1:1の光を照射して栽培することによって、蛍光灯又は太陽光で栽培したナスタチウムと比較して、抗酸化効果、マトリックスメタロプロテアーゼ(MMP)阻害効果及び美白効果から選ばれる一種又は二種以上の効果を高めたナスタチウム又は、水、低級アルコール及び液状多価アルコールから選ばれる一種又は二種以上の溶媒によって抽出される抽出物を含有することを特徴とする医薬品。
(5)波長域570〜730nmと400〜515nmとの光合成光量子束密度(PPFD)比が8:1〜1:1の光を照射して栽培することによって、蛍光灯又は太陽光で栽培したナスタチウムと比較して、抗酸化効果、マトリックスメタロプロテアーゼ(MMP)阻害効果及び美白効果から選ばれる一種又は二種以上の効果を高めたナスタチウム又は、水、低級アルコール及び液状多価アルコールから選ばれる一種又は二種以上の溶媒によって抽出される抽出物を含有することを特徴とする食品。
(6)波長域570〜730nm及び/又は400〜515nmの光を照射して栽培したナスタチウムの、水、低級アルコール及び液状多価アルコールから選ばれる一種又は二種以上の溶媒によって抽出される抽出物を含有することを特徴とする皮膚外用剤。
(7)波長域570〜730nm及び/又は400〜515nmの光を照射して栽培したナスタチウム、又は、そのナスタチウムの水、低級アルコール及び液状多価アルコールから選ばれる一種又は二種以上の溶媒によって抽出される抽出物。
(1) Water, lower alcohols and liquid polyhydric alcohols of nastathium cultivated by irradiating light having a photosynthetic photon flux density (PPFD) ratio of 8: 1 to 1: 1 in the wavelength range of 570 to 730 nm and 400 to 515 nm. An external preparation for skin, which comprises an extract from one or more solvents selected from the above.
(2) The external preparation for skin according to claim 1, wherein the photosynthetic photon flux density (PPFD) ratio between the wavelength range of 570 to 730 nm and 400 to 515 nm is 4: 1 to 2: 1.
(3) Nastatium cultivated with a fluorescent lamp or sunlight by cultivating it by irradiating it with light having a photosynthetic photon flux density (PPFD) ratio of 8: 1 to 1: 1 in the wavelength range of 570 to 730 nm and 400 to 515 nm. Nastatium, which is characterized by enhancing one or more effects selected from an antioxidant effect, a matrix metalloproteinase (MMP) inhibitory effect, and a whitening effect.
(4) Nastatium cultivated with a fluorescent lamp or sunlight by cultivating it by irradiating it with light having a photosynthetic photon flux density (PPFD) ratio of 8: 1 to 1: 1 in the wavelength range of 570 to 730 nm and 400 to 515 nm. One or two or more enhanced effects selected from antioxidative effect, matrix metalloproteinase (MMP) inhibitory effect and whitening effect, or one selected from water, lower alcohol and liquid polyhydric alcohol. A drug characterized by containing an extract extracted by two or more kinds of solvents.
(5) Nastatium cultivated with a fluorescent lamp or sunlight by cultivating it by irradiating it with light having a photosynthetic photon flux density (PPFD) ratio of 8: 1 to 1: 1 in the wavelength range of 570 to 730 nm and 400 to 515 nm. One or two or more enhanced effects selected from antioxidative effect, matrix metalloproteinase (MMP) inhibitory effect and whitening effect, or one selected from water, lower alcohol and liquid polyhydric alcohol. A food characterized by containing an extract extracted by two or more kinds of solvents.
(6) An extract of nastathium cultivated by irradiating light in the wavelength range of 570 to 730 nm and / or 400 to 515 nm, which is extracted by one or more solvents selected from water, lower alcohols and liquid polyhydric alcohols. A skin external preparation characterized by containing.
(7) Extracted with one or more solvents selected from nastatium cultivated by irradiating light in the wavelength range of 570 to 730 nm and / or 400 to 515 nm, or water, lower alcohol and liquid polyhydric alcohol of the nastatium. Extract to be.

本発明のナスタチウム又はその抽出物は、優れた抗酸化効果、マトリックスメタロプロテアーゼ(MMP)阻害効果及び美白効果を有しており、医薬品、医薬部外品、化粧品、食品の分野において貢献できるものである。 The nastatium or its extract of the present invention has an excellent antioxidant effect, a matrix metalloproteinase (MMP) inhibitory effect and a whitening effect, and can contribute to the fields of pharmaceuticals, quasi-drugs, cosmetics and foods. is there.

以下に、本発明について詳細に述べる。 The present invention will be described in detail below.

本発明に用いるナスタチウムの抽出物とは、ノウゼンハレン科トロパエオルム属のノウゼンハレン、別名キンレンカ(学名:Tropaeolum majus)の花、実、種子、茎、葉、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。また、本発明においては、抽出物の代わりに、植物体のまま使用することもでき、生のままでも、乾燥して用いることもでき、目的によって使い分けることができる。さらには、抽出物と植物体を併用することもできる。 The extract of Nasturtium used in the present invention is extracted from a part or whole plant such as flowers, fruits, seeds, stems, leaves, roots, etc. It was done. The extraction method is not particularly limited, and for example, it may be extracted by heating or may be extracted at room temperature. Further, in the present invention, instead of the extract, the plant body can be used as it is, or it can be used raw or dried, and can be used properly depending on the purpose. Furthermore, the extract and the plant can be used in combination.

栽培方法としては、土を用いた栽培や水耕栽培で行うことができる。水耕栽培で行う場合には、種子を播種後、出根した状態で、水耕栽培に供することができる。栽培は、温度、光、二酸化炭素濃度が制御された施設で栽培することが好ましい。栽培温度は、15〜30℃、好ましくは20〜25℃である。栽培期間は、照射する条件によって異なるが、概ね10〜30日で収穫できる。これ以上栽培することも可能である。 As a cultivation method, it can be cultivated using soil or hydroponics. In the case of hydroponics, the seeds can be sown and then used for hydroponics in a rooted state. Cultivation is preferably carried out in a facility where the temperature, light and carbon dioxide concentration are controlled. The cultivation temperature is 15 to 30 ° C, preferably 20 to 25 ° C. The cultivation period varies depending on the irradiation conditions, but it can be harvested in about 10 to 30 days. It is also possible to grow more.

光源は、植物の栽培施設で用いる光源などを使用することができ、発光ダイオード(LED)、レーザーダイオードなどの光半導体素子があげられるが、特定の範囲の波長域が選択的に照射できる光源であればLEDに限らない。 As the light source, a light source used in a plant cultivation facility or the like can be used, and an optical semiconductor element such as a light emitting diode (LED) or a laser diode can be used, but a light source capable of selectively irradiating a specific wavelength range. If there is, it is not limited to LED.

ナスタチウムの栽培において、照射する波長としては、波長域400〜515nmの青色光、570〜730nmの赤色光であることが好ましく、波長域430〜460nm、630〜680nmの光がさらに好ましい。これらの光は、同時に照射することが最も好ましい。このときの波長は、照射スペクトルの極大波長(ピーク波長)のことをいう。このような波長のピークを有する光源であれば、独自に作成したものや市販のものを使用することもできる。また、上記波長を選択的に照射できるように、光学フィルタを用いても良い。上記の2種の範囲の光に加え、太陽光や蛍光灯などの光源を使用することもできる。 In the cultivation of nasturtium, the wavelength to be irradiated is preferably blue light having a wavelength range of 400 to 515 nm and red light having a wavelength range of 570 to 730 nm, and more preferably light having a wavelength range of 430 to 460 nm and 630 to 680 nm. It is most preferable to irradiate these lights at the same time. The wavelength at this time refers to the maximum wavelength (peak wavelength) of the irradiation spectrum. As long as it is a light source having a peak of such a wavelength, an original one or a commercially available one can be used. Further, an optical filter may be used so that the above wavelength can be selectively irradiated. In addition to the above two types of light, a light source such as sunlight or a fluorescent lamp can also be used.

照射する光量としては、光合成有効光量子束密度(PPFD)として表される。発光体を2種組み合わせて照射する場合には、その合計の光量を意味する。その光量は、発芽後は10〜300μmol・m−2−1が好ましく、50〜200μmol・m−2−1がさらに好ましい。この範囲外の光強度の場合は、生育障害、生育不良になる場合がある。照射は、ナスタチウムの上部10〜50cmの位置から照射することが好ましい。照射時間は、植物の特性や目的に応じて適宜変更できるが、6時間以上が好ましく、12〜24時間がより好ましい。 The amount of light to be irradiated is expressed as photosynthetic effective photon flux density (PPFD). When irradiating two types of illuminants in combination, it means the total amount of light. The amount of light is preferably 10 to 300 μmol · m -2 s -1 after germination, and more preferably 50 to 200 μmol · m -2 s -1 . If the light intensity is outside this range, growth may be impaired or poor growth may occur. Irradiation is preferably performed from a position 10 to 50 cm above the nasturtium. The irradiation time can be appropriately changed according to the characteristics and purpose of the plant, but is preferably 6 hours or more, and more preferably 12 to 24 hours.

赤色と青色の光量比においては、それぞれのPPFDの比を意味しており、収量や有効性など目的に応じて選択が可能である。 The red and blue light intensity ratio means the ratio of each PPFD, and can be selected according to the purpose such as yield and effectiveness.

中でも、植物体の収量を高めるには、赤色と青色の光量比が1:0〜2:1が好ましく、その中でも特に、赤色と青色の光量比が4:1〜2:1に高い収量が得られた。 Among them, in order to increase the yield of plants, the light intensity ratio of red and blue is preferably 1: 0 to 2: 1, and among them, the light intensity ratio of red and blue is particularly high at 4: 1 to 2: 1. Obtained.

活性酸素消去作用(フリーラジカル捕捉除去作用)においては、赤色と青色の光量比が1:0〜0:1が効果の面で好ましく、4:1〜0:1がより好ましい。その中でも特に、赤色と青色の光量比が2:1〜0:1が最も好ましい。 In the active oxygen scavenging action (free radical capture / removal action), the light intensity ratio of red and blue is preferably 1: 0 to 0: 1 in terms of effect, and more preferably 4: 1 to 0: 1. Among them, the ratio of red to blue light is most preferably 2: 1 to 0: 1.

MMP−1 mRNA発現抑制作用においては、赤色と青色の光量比が1:0〜2:1が効果の面で好ましい。その中でも特に、赤色と青色の光量比が8:1〜3:1が最も好ましい。 In the MMP-1 mRNA expression inhibitory action, the light intensity ratio of red and blue is preferably 1: 0 to 2: 1 in terms of effect. Among them, the ratio of red to blue light is most preferably 8: 1-3: 1.

MMP−2 mRNA発現抑制作用においては、赤色と青色の光量比が3:1が効果の面で好ましい。 In the MMP-2 mRNA expression inhibitory action, a light intensity ratio of red to blue of 3: 1 is preferable in terms of effect.

メラニン生成抑制作用においては、赤色と青色の光量比が8:1〜1:1が効果の面で好ましい。その中でも特に、赤色と青色の光量比が4:1〜2:1が最も好ましい。 In the melanin production inhibitory action, a red to blue light intensity ratio of 8: 1 to 1: 1 is preferable in terms of effect. Among them, the ratio of red to blue light is most preferably 4: 1 to 2: 1.

以上のことを総じていえば、赤色と青色の光量比が8:1〜1:1が好ましく、4:1〜2:1が最も好ましい。 Overall, the ratio of red to blue light is preferably 8: 1 to 1: 1 and most preferably 4: 1 to 2: 1.

抽出溶媒としては、例えば、水、低級アルコール(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)、液状多価アルコール(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。 Examples of the extraction solvent include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol, 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.) Can be mentioned. 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.

上記抽出物は、抽出した溶液のまま用いても良く、必要に応じて、濃縮、希釈及び濾過処理、活性炭等による脱色、脱臭処理等をして用いても良い。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。また、サラダなど、生で食することもできる。 The above-mentioned extract may be used as it is in the extracted solution, or may be used after concentration, dilution and filtration treatment, decolorization with activated carbon or the like, deodorization treatment and the like, if necessary. 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. You can also eat it raw, such as salad.

本発明の外用剤又は内用剤には、食品も含むものとし、これには、上記植物体及び/又は抽出物をそのまま使用しても良く、これら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、酸味料等の成分を配合することもできる。 The external preparation or internal preparation of the present invention shall also include foods, and the above-mentioned plants and / or extracts may be used as they are, and cosmetics and pharmaceuticals may be used as long as these effects are not impaired. Oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, which are ingredients used in external products, pharmaceuticals, foods, etc. Ingredients such as agents, powders, ultraviolet absorbers, thickeners, pigments, antioxidants, whitening agents, chelating agents, excipients, film agents, sweeteners and acidulants can also be blended.

本発明は、医薬品、医薬部外品、化粧品、食品に用いることができ、その剤型としては、例えば、化粧水、クリーム、マッサージクリーム、乳液、ゲル剤、エアゾール剤、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、ペースト剤、プラスター剤、エッセンス、散剤、丸剤、錠剤、注射剤、坐剤、乳剤、カプセル剤、顆粒剤、液剤(チンキ剤、流エキス剤、酒精剤、懸濁剤、リモナーデ剤等を含む)、錠菓、飲料、ティーバッグ、スパイス等が挙げられる。 The present invention can be used in pharmaceuticals, non-pharmaceutical products, cosmetics, and foods, and its dosage forms include, for example, lotions, creams, massage creams, emulsions, gels, aerosols, packs, cleaning agents, and baths. Agents, foundations, dusting, lipsticks, ointments, poultices, pastes, plasters, essences, powders, pills, tablets, injections, suppositories, emulsions, capsules, granules, liquids (tinki agents, flow extracts) , Suppositories, suspending agents, limonade agents, etc.), tablets, beverages, tea bags, spices, etc.

本発明に用いる上記抽出物の配合量は、外用の場合、全量に対し、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。さらに、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%を越えて配合した場合、効果の増強は認められにくく不経済である。一方、内用の場合、投与量は年齢、体重、症状、治療効果、投与方法、処理時間等により異なるが、通常、成人1人当たりの1日の量としては、5mg以上が好ましく、10mg〜5gがより好ましい。さらに、100mg〜1gが最も好ましい。 In the case of external use, the blending amount 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, based on the total amount. 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. When it is blended in excess of 10% by weight, it is difficult to recognize the enhancement of the effect and it is uneconomical. On the other hand, in the case of internal use, the dose varies depending on age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., but usually, the daily dose per adult is preferably 5 mg or more, preferably 10 mg to 5 g. Is more preferable. Further, 100 mg to 1 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ナスタチウムの抽出物の製造例、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、実施例に示す配合量の部とは重量部を示す。 Next, in order to explain the present invention in detail, examples of production, experimental examples, and formulation examples of the extract of nastathium used in the present invention will be given, but the present invention is not limited thereto. The% shown in the production example indicates a weight%, and the compounding amount portion shown in the example indicates a weight portion.

(1)実験材料および生育条件
水分を含んだメッシュにナスタチウムの種子を播種し、温度22〜24℃・暗所で発芽させ、これをスポンジに包み、22〜24℃で24時間白色蛍光灯下で栽培し、育苗した。その後、水耕栽培装置を用いて、室温21〜23℃で24時間、植物の真上30cmの位置から、青色LED(ピーク波長450nm)及び赤色LED(ピーク波長660nm)を同時に照射し、赤色と青色LEDの合計光合成有効光量子束密度100μmol・m−2−1となるように、赤色と青色の光量比を1:0〜0:1にして、栽培を行った。また、比較例1として光合成有効光量子束密度100μmol・m−2−1となるように白色蛍光灯下で栽培を行い、比較例2として太陽光下で栽培を行った。なお、栽培中は光量比を変えなかった。4週間栽培した後、収穫し、生ナスタチウムを得た。これを約60℃で温風乾燥させることで、ナスタチウムの乾燥物を得た(表1)。
(1) Experimental materials and growth conditions Nastatium seeds are sown on a mesh containing water, germinated in a dark place at a temperature of 22 to 24 ° C, wrapped in a sponge, and placed under a white fluorescent lamp at 22 to 24 ° C for 24 hours. Cultivated and raised seedlings. Then, using a hydroponic cultivation device, the blue LED (peak wavelength 450 nm) and the red LED (peak wavelength 660 nm) are simultaneously irradiated from a position 30 cm above the plant for 24 hours at room temperature 21 to 23 ° C. Cultivation was carried out with the light intensity ratio of red and blue set to 1: 0 to 0: 1 so that the total photosynthetic effective photon flux density of the blue LED was 100 μmol · m -2 s -1 . Further, as Comparative Example 1, cultivation was carried out under a white fluorescent lamp so that the photosynthetic effective photon bundle density was 100 μmol · m- 2 s- 1, and as Comparative Example 2, cultivation was carried out under sunlight. The light intensity ratio was not changed during cultivation. After cultivating for 4 weeks, it was harvested to obtain raw nasturtium. This was dried with warm air at about 60 ° C. to obtain a dried product of nasturtium (Table 1).

(2)抽出
製造例1A 熱水抽出物
乾燥物10gに精製水200mLを加え、95〜100℃で2時間抽出した後、濾過し、その濾液を濃縮し、凍結乾燥して熱水抽出物を得た(表2)。
(2) Extraction
Production Example 1A Hot water extract 200 mL of purified water is added to 10 g of the dried product, extracted at 95 to 100 ° C. for 2 hours, filtered, the filtrate is concentrated, and freeze-dried to obtain the hot water extract. Obtained (Table 2).

製造例1B 50%エタノール抽出物
乾燥物10gに50%エタノール200mLを加え、常温で7日間抽出した後、濾過し、その濾液を濃縮乾固して、50%エタノール抽出物を得た(表2)。
Production Example 1B 50% ethanol extract 200 mL of 50% ethanol was added to 10 g of the dried product, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness to obtain a 50% ethanol extract. (Table 2).

製造例1C エタノール抽出物
乾燥物10gにエタノール200mLを加え、常温で7日間抽出した後、濾過し、その濾液を濃縮乾固して、エタノール抽出物を得た(表2)。
Production Example 1C Ethanol extract 200 mL of ethanol was added to 10 g of the dried product, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness to obtain an ethanol extract (Table 2).

上記と同様に、赤色と青色LEDの合計光合成有効光量子束密度100μmol・m−2−1となるように、赤色と青色の光量比を変化させて栽培したナスタチウムまたは比較例1として光合成有効光量子束密度100μmol・m−2−1となるように白色蛍光灯下で上記の生育条件と同様に栽培したナスタチウム、比較例2として太陽光で栽培したナスタチウムを用い、上記の製造例1A〜1Cと同様に抽出し、製造例2A〜7C、比較製造例1A〜1C、比較製造例2A〜2Cとした(表2)。 Similar to the above, Nastatium cultivated by changing the light intensity ratio of red and blue so that the total photosynthetic effective photon bundle density of red and blue LEDs is 100 μmol · m -2 s -1 , or photosynthetic effective photon as Comparative Example 1. Nastatium cultivated under white fluorescent lamps under the same growth conditions as above so that the bundle density is 100 μmol · m -2 s -1, and Nastatium cultivated in sunlight as Comparative Example 2 were used, and Production Examples 1A to 1C described above were used. The same extraction was performed as in Production Examples 2A to 7C, Comparative Production Examples 1A to 1C, and Comparative Production Examples 2A to 2C (Table 2).

実験例1 活性酸素消去作用
フリーラジカル捕捉除去作用の評価を行った。陽性対照としてはアスコルビン酸を用いた。フリーラジカルのモデルとしては、安定なフリーラジカルであるα,α−ジフェニル−β−ピクリルヒドラジル(以下DPPHとする)を用い、試料と一定の割合で一定時間反応させ、減少するラジカルの量を波長517nmの吸光度の減少量から測定した。
Experimental Example 1 Active oxygen scavenging action Free radical capture and removal action was evaluated. Ascorbic acid was used as a positive control. As a model of free radicals, stable free radicals α, α-diphenyl-β-picrylhydrazil (hereinafter referred to as DPPH) are used, and the amount of radicals decreases after reacting with a sample at a constant ratio for a certain period of time. Was measured from the amount of decrease in absorbance at a wavelength of 517 nm.

フリーラジカル捕捉除去作用の測定方法
各試料を、熱水抽出物と50%EtOH抽出物では最終濃度0.1〜1.0mg/mL、100%EtOH抽出物では最終濃度0.03〜0.05mg/mL(アスコルビン酸は0.01mg/mL)となるように加えた0.1M酢酸緩衝液(pH5.5)2mLに無水エタノール2mL及び0.5mM DPPH無水エタノール溶液1mLを加えて反応液とした。その後、37℃で30分間反応させ、水を対照として波長517nmの吸光度を測定した。(なお、100%EtОH抽出物に関しては、70分間反応させた。)また、ブランクとして試料の代わりに精製水を加えた反応液を用いて吸光度を測定した。ブランクと比較して、吸光度が50%減少したときの試料の濃度(IC50)を算出した。
Method for measuring free radical capture and removal effect Each sample has a final concentration of 0.1 to 1.0 mg / mL for hot water extract and 50% EtOH extract, and a final concentration of 0.03 to 0.05 mg for 100% EtOH extract. 2 mL of absolute ethanol and 1 mL of 0.5 mM DPPH absolute ethanol solution were added to 2 mL of 0.1 M acetate buffer (pH 5.5) added so as to be / mL (0.01 mg / mL for ascorbic acid) to prepare a reaction solution. .. Then, the reaction was carried out at 37 ° C. for 30 minutes, and the absorbance at a wavelength of 517 nm was measured using water as a control. (The 100% EtOH extract was reacted for 70 minutes.) In addition, the absorbance was measured using a reaction solution containing purified water instead of the sample as a blank. The concentration of the sample (IC 50 ) when the absorbance was reduced by 50% as compared to the blank was calculated.

これらの試験結果を表3に示した。本発明の抽出物は、安定で優れたフリーラジカル捕捉除去作用を有していることが認められた。特に、赤色と青色の光量比が1:0〜0:1が好ましく、4:1〜0:1がより好ましく、2:1〜0:1が最も好ましい。これらのとき、従来技術である太陽光による栽培品と比較して顕著に高い効果が認められた。なお、アスコルビン酸は、100℃、1時間の熱処理で失活するが、本発明の抽出物は、活性に変化はなかった。 The results of these tests are shown in Table 3. It was found that the extract of the present invention has a stable and excellent free radical trapping and removing action. In particular, the light intensity ratio of red and blue is preferably 1: 0 to 0: 1, more preferably 4: 1 to 0: 1, and most preferably 2: 1 to 0: 1. At these times, a significantly higher effect was observed as compared with the conventional cultivated product using sunlight. Ascorbic acid was inactivated by heat treatment at 100 ° C. for 1 hour, but the activity of the extract of the present invention did not change.

実験例2 マトリックスメタロプロテアーゼ(MMP)阻害効果
MMP−1及びMMP−2 mRNA発現量の測定を行った。ヒト皮膚線維芽細胞(NB1RGB)を60mm dishに1×10個播種し、10%FBSを含むDMEM培養液にて、37℃、5%CO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、MMP−1 mRNA発現量測定では各試料を最終濃度1μg/mLを添加しMMP−2 mRNA発現量測定では各試料を最終濃度10μg/mLを添加したDMEM培養液にて、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TRIZOL Reagent(Invitrogen)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、SuperScriptIII Platinum Two−Step qRT−PCR Kit with SYBR Green(Invitrogen)を用いた。すなわち、500ngの総RNAを逆転写反応後、PCR反応(95℃:15秒間、60℃:30秒間、40cycles)を行った。その他の操作は定められた方法に従い、MMP−1及びMMP−2 mRNAの発現量を、内部標準であるβ―actin mRNAの発現量に対する割合として求めた。MMP発現量は、コントロールのMMP mRNAの発現量に対する試料添加群のMMP 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 2 Matrix metalloproteinase (MMP) inhibitory effect The expression levels of MMP-1 and MMP-2 mRNA were measured. Human skin fibroblasts (NB1RGB) were seeded in 1 × 10 5 pieces on a 60 mm dish and cultured in DMEM culture medium containing 10% FBS under 37 ° C. and 5% CO 2 conditions. When the condition became confluent, each sample was added with a final concentration of 1 μg / mL for MMP-1 mRNA expression measurement, and each sample was added to a DMEM culture solution with a final concentration of 10 μg / mL for MMP-2 mRNA expression measurement. After culturing for 24 hours, total RNA was extracted. Extraction of total RNA from cells was performed using a TRIZOL Reagent (Invitrogen), 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. As the real-time RT-PCR method, SuperScriptIII Platinum Two-Step qRT-PCR Kit with SYBR Green (Invitrogen) was used. That is, after a reverse transcription reaction of 500 ng of total RNA, a PCR reaction (95 ° C: 15 seconds, 60 ° C: 30 seconds, 40 cycles) was performed. For other operations, the expression levels of MMP-1 and MMP-2 mRNA were determined as a ratio to the expression level of β-actin mRNA, which is an internal standard, according to a predetermined method. The MMP expression level was calculated as the ratio of the expression level of MMP mRNA in the sample-added group to the expression level of control MMP mRNA. The primers used to measure the expression level of each gene are as follows.

MMP−1用のプライマーセット
GGGAGATCATCGGGACAACTC(配列番号1)
TGAGCATCCCCTCCAATACC(配列番号2)
MMP−2用のプライマーセット
CCGTCGCCCATCATCAA(配列番号3)
CTTCTGCATCTTCTTTAGTGTGTCCTT(配列番号4)
β―Actin用のプライマーセット
CACTCTTCCAGCCTTCCTTCC(配列番号5)
GTGTTGGCGTACAGGTCTTTG(配列番号6)
Primer set for MMP-1 GGGAGATCATCGGGACAACTC (SEQ ID NO: 1)
TGAGCATCCCCCTCCAAATACC (SEQ ID NO: 2)
Primer set for MMP-2 CCGTCGCCCATCATCAA (SEQ ID NO: 3)
CTTTGCATCTTCTTTAGTGTGTCCTT (SEQ ID NO: 4)
Primer set for β-Actin CACTCTTCCAGCCTTCCTCC (SEQ ID NO: 5)
GTGTTGGGCGTACAGGTCTTG (SEQ ID NO: 6)

これらの実験結果を表4、表5に示した。その結果、本発明の抽出物は、優れたMMP発現抑制効果(MMP阻害効果)が認められた。MMP−1発現抑制効果では、特に、赤色と青色の光量比が1:0〜2:1に高い効果が認められた。その中でも特に、赤色と青色の光量比が8:1〜3:1に高い効果が認められた。また、MMP−2では、赤色と青色の光量比が3:1に高い効果が認められた。 The results of these experiments are shown in Tables 4 and 5. As a result, the extract of the present invention was found to have an excellent MMP expression inhibitory effect (MMP inhibitory effect). As for the MMP-1 expression suppressing effect, a particularly high effect was observed in which the light intensity ratio of red and blue was 1: 0 to 2: 1. Among them, a particularly high effect was observed in which the light intensity ratio of red and blue was 8: 1-3: 1. Further, in MMP-2, a high effect was observed in which the light intensity ratio of red and blue was 3: 1.

実験例3 メラニン生成抑制試験
対数増殖期にあるB16マウスメラノーマ細胞を60mm dishに3×10個播種し、各試料(最終濃度100μg/mL)を含むEagles’MEM(10%牛胎児血清含有)培地にて、37℃、5%CO条件下で5日間培養した。次に、細胞をdishから剥離し、超音波破砕した後、4N NaOHを加え60℃で2時間の処理を行い、分光光度計でO.D.475nmを測定した。尚、超音波処理後の細胞破砕液についてLowryの方法(J.Biol.Chem.,193,265−275,1951)にてタンパク定量し、タンパク量当りのメラニン量を算出、試料未添加のメラニン生成量をコントロールとし、コントロールに対する試料添加時のメラニン生成量の値からメラニン生成抑制率を算出した。
Experimental Example 3 Melanin production suppression test Eagles'MEM (containing 10% fetal bovine serum) containing 3 × 10 4 B16 mouse melanoma cells in the logarithmic growth phase on a 60 mm dish and containing each sample (final concentration 100 μg / mL). The cells were cultured in medium at 37 ° C. under 5% CO 2 conditions for 5 days. Next, the cells were exfoliated from the dish, ultrasonically crushed, 4N NaOH was added, and the cells were treated at 60 ° C. for 2 hours. D. 475 nm was measured. The cell crushed solution after the ultrasonic treatment was quantified by the Lowry method (J. Biol. Chem., 193,265-275,1951), the amount of melanin per protein amount was calculated, and the amount of melanin without sample was added. Using the amount of production as a control, the melanin production suppression rate was calculated from the value of the amount of melanin produced when the sample was added to the control.

これらの試験結果を表6に示した。本発明の抽出物は、優れたメラニン生成抑制作用を有していることが認められた。特に、赤色と青色の光量比が8:1〜1:1に高い効果が認められた。その中でも特に、赤色と青色の光量比が4:1〜2:1に高い効果が認められた。 The results of these tests are shown in Table 6. It was found that the extract of the present invention has an excellent melanin production inhibitory effect. In particular, a high effect was observed with a light intensity ratio of red and blue of 8: 1 to 1: 1. Among them, a particularly high effect was observed in which the light intensity ratio of red and blue was 4: 1 to 2: 1.

処方例1 化粧水
処方 配合量(部)
1.製造例3Aの抽出物 1.0
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 compounding amount (part)
1. 1. Extract of Production Example 3A 1.0
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] Components 1 to 6 and 11 having a total amount of 100 in purified water and components 7 to 10 are uniformly dissolved, and both are mixed and filtered to obtain a product.

処方例2 クリーム
処方 配合量(部)
1.製造例4Aの抽出物 0.5
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 0.25
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 compounding amount (part)
1. 1. Extract of Production Example 4A 0.5
2. 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 0.25
12.1,3-butylene glycol 8.5
13. [Manufacturing method] Ingredients 2 to 9 having a total amount of 100 in purified water are dissolved 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 to prepare an aqueous phase at 75 ° C. 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.

処方例2において、製造例4Aの抽出物を製造例1Aの抽出物、製造例7Aの抽出物及び製造例4Bの抽出物に置き換えたものを処方例3、4及び5とした。 In Formulation Example 2, the extracts of Production Example 4A were replaced with the extracts of Production Example 1A, the extracts of Production Example 7A, and the extracts of Production Example 4B, which were designated as Formulation Examples 3, 4 and 5.

処方例6 乳液
処方 配合量(部)
1.製造例2Aの抽出物 1.0
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2〜8を加熱溶解して混合し、70℃に保ち油相とする。成分1及び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 6 Emulsion prescription compounding amount (part)
1. 1. Extract of Production Example 2A 1.0
2. 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 2 to 8 having a total amount of 100 in purified water are dissolved by heating and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 and 10 to 13 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 mixture is cooled while stirring, component 9 is added at 45 ° C, and the product is further cooled to 30 ° C to obtain a product.

処方例7 ゲル剤
処方 配合量(部)
1.製造例4Cの抽出物 0.001
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 7 Gel agent Prescription compounding amount (part)
1. 1. Extract of Production Example 4C 0.001
2. 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8 パック
処方 配合量(部)
1.製造例5Aの抽出物 0.1
2.製造例5Bの抽出物 0.1
3.ポリビニルアルコール 12.0
4.エタノール 5.0
5.1,3‐ブチレングリコール 8.0
6.パラオキシ安息香酸メチル 0.2
7.ポリオキシエチレン硬化ヒマシ油(20E.O.) 0.5
8.クエン酸 0.1
9.クエン酸ナトリウム 0.3
10.香料 適量
11.精製水にて全量を100とする
[製造方法]成分1〜11を均一に溶解し製品とする。
Prescription example 8 pack prescription compounding amount (part)
1. 1. Extract of Production Example 5A 0.1
2. 2. Extract of Production Example 5B 0.1
3. 3. Polyvinyl alcohol 12.0
4. Ethanol 5.0
5.1,3-butylene glycol 8.0
6. Methyl paraoxybenzoate 0.2
7. Polyoxyethylene hydrogenated castor oil (20EO) 0.5
8. Citric acid 0.1
9. Sodium citrate 0.3
10. Appropriate amount of fragrance 11. [Manufacturing method] Ingredients 1 to 11 having a total amount of 100 are uniformly dissolved in purified water to prepare a product.

処方例9 ファンデーション
処方 配合量(部)
1.製造例3Aの抽出物 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をよく膨潤させ、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 9 Foundation prescription compounding amount (part)
1. 1. Extract of Production Example 3A 1.0
2. 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 19 is well swollen with Ingredient 9, followed by Additions 1 and 10-13 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. After that, it is cooled, component 18 is added at 45 ° C., and the product is cooled to 30 ° C. with stirring.

処方例10 浴用剤
処方 配合量(部)
1.製造例6Aの抽出物 5.0
2.製造例6Bの抽出物 1.0
3.炭酸水素ナトリウム 50.0
4.黄色202号(1) 適量
5.香料 適量
6.硫酸ナトリウムにて全量を100とする
[製造方法]成分1〜6を均一に混合し製品とする。
Prescription example 10 Bath agent Prescription compounding amount (part)
1. 1. Extract of Production Example 6A 5.0
2. 2. Extract of Production Example 6B 1.0
3. 3. Sodium bicarbonate 50.0
4. Yellow No. 202 (1) Appropriate amount 5. Appropriate amount of fragrance 6. [Manufacturing method] Ingredients 1 to 6 with sodium sulfate to make the total amount 100 are uniformly mixed to prepare a product.

処方例11 軟膏
処方 配合量(部)
1.製造例4Bの抽出物 0.5
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 11 Ointment prescription compounding amount (part)
1. 1. Extract of Production Example 4B 0.5
2. 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 dissolved 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12 散剤
処方 配合量(部)
1.製造例4Aの抽出物 20.0
2.乾燥コーンスターチ 30.0
3.微結晶セルロース 50.0
[製造方法]成分1〜3を混合し、散剤とする。
Prescription example 12 Powder prescription compounding amount (part)
1. 1. Extract of Production Example 4A 20.0
2. 2. Dried cornstarch 30.0
3. 3. Microcrystalline Cellulose 50.0
[Manufacturing method] Ingredients 1 to 3 are mixed to prepare a powder.

処方例13 錠剤
処方 配合量(部)
1.製造例4Aの抽出物 3.0
2.乾燥コーンスターチ 27.0
3.カルボキシメチルセルロースカルシウム 20.0
4.微結晶セルロース 40.0
5.ポリビニルピロリドン 7.0
6.タルク 3.0
[製造方法]成分1〜4を混合し、次いで成分5の水溶液を結合剤として加えて顆粒成形する。成形した顆粒に成分6を加えて打錠する。1錠0.52gとする。
Prescription example 13 Tablets Prescription compounding amount (part)
1. 1. Extract of Production Example 4A 3.0
2. 2. Dried cornstarch 27.0
3. 3. Carboxymethyl cellulose calcium 20.0
4. Microcrystalline Cellulose 40.0
5. Polyvinylpyrrolidone 7.0
6. Talc 3.0
[Manufacturing method] Ingredients 1 to 4 are mixed, and then an aqueous solution of ingredient 5 is added as a binder to form granules. Ingredient 6 is added to the molded granules and the mixture is locked. One tablet weighs 0.52 g.

処方例14 錠菓
処方 配合量(部)
1.製造例5Aの抽出物 0.5
2.乾燥コーンスターチ 50.0
3.エリスリトール 40.0
4.クエン酸 5.0
5.ショ糖脂肪酸エステル 3.0
6.香料 適量
7.精製水にて全量を100とする
[製造方法]成分1〜4及び7を混合し、顆粒成形する。成形した顆粒に成分5及び6を加えて打錠する。1粒1.0gとする。
Prescription example 14 Tablet confectionery prescription compounding amount (part)
1. 1. Extract of Production Example 5A 0.5
2. 2. Dried cornstarch 50.0
3. 3. Erythritol 40.0
4. Citric acid 5.0
5. Sucrose fatty acid ester 3.0
6. Appropriate amount of fragrance 7. [Manufacturing method] Ingredients 1 to 4 and 7 having a total amount of 100 are mixed with purified water to form granules. Ingredients 5 and 6 are added to the molded granules and the mixture is locked. One grain is 1.0 g.

処方例15 飲料
処方 配合量(部)
1.製造例5Aの抽出物 2.0
2.果糖ブドウ糖液糖 12.5
3.クエン酸 0.1
4.香料 0.05
5.精製水にて全量を100とする
[製造方法]成分1〜5を混合し、飲料とする。
Prescription example 15 Beverage prescription compounding amount (part)
1. 1. Extract of Production Example 5A 2.0
2. 2. Fructose-glucose liquid sugar 12.5
3. 3. Citric acid 0.1
4. Fragrance 0.05
5. [Manufacturing method] Ingredients 1 to 5 having a total amount of 100 are mixed with purified water to prepare a beverage.

処方例16 粉末飲料
処方 配合量(部)
1.製造例7Aの抽出物 10.0
2.粉糖 65.0
3.粉末ピーチ果汁 15.0
4.L−アスコルビン酸 8.0
5.結晶クエン酸 1.2
6.クエン酸ナトリウム 0.75
7.アスパルテーム 0.02
8.粉末ピーチ香料 0.03
[製造方法]成分1〜8を混合し、粉末飲料とする。
Prescription example 16 Powdered beverage Prescription compounding amount (part)
1. 1. Extract of Production Example 7A 10.0
2. 2. Powdered sugar 65.0
3. 3. Powdered peach juice 15.0
4. L-ascorbic acid 8.0
5. Crystalline citric acid 1.2
6. Sodium citrate 0.75
7. Aspartame 0.02
8. Powdered peach flavor 0.03
[Manufacturing method] Ingredients 1 to 8 are mixed to prepare a powdered beverage.

処方例17 ハーブティ
処方 配合量(部)
1.ナスタチウム乾燥物(比較例を除く実施例1の表1) 1.0
2.ペパーミント 0.5
3.ローズヒップ 0.5
[製造方法]成分1〜3を混合し、ティーバッグに2gを封入してハーブティーとする。
Prescription example 17 Herbal tea prescription compounding amount (part)
1. 1. Nasturtium dried product (Table 1 of Example 1 excluding comparative examples) 1.0
2. 2. Peppermint 0.5
3. 3. Rosehip 0.5
[Manufacturing method] Ingredients 1 to 3 are mixed, and 2 g is sealed in a tea bag to make herbal tea.

以上のことから、特定の波長域を有する光を照射して栽培したナスタチウムやその抽出物は、優れた抗酸化効果、マトリックスメタロプロテアーゼ(MMP)阻害効果及び美白効果を示し、これらを含有する皮膚外用剤又は内用剤は特に有効である。 From the above, nastatium and its extract cultivated by irradiating light having a specific wavelength range show excellent antioxidant effect, matrix metalloproteinase (MMP) inhibitory effect and whitening effect, and the skin containing these. External or internal preparations are particularly effective.

Claims (3)

波長域570〜730nmの赤色光と400〜515nmの青色光とを、光合成光量子束密度(PPFD)が合計で50〜200μmol・m −2 −1 、赤色光と青色光の比が2:1〜1:1となるように照射し、栽培温度20〜25℃で10〜30日間の栽培条件で栽培する、ナスタチウムの栽培方法であって、同じ光合成光量子束密度の蛍光灯光又は太陽光を照射し、同じ栽培条件で栽培したナスタチウムと比較して、抗酸化効果が高いことを特徴とするナスタチウムの栽培方法The total photosynthetic photon flux density (PPFD) of red light in the wavelength range of 570 to 730 nm and blue light of 400 to 515 nm is 50 to 200 μmol · m- 2 s -1 , and the ratio of red light to blue light is 2: 1. It is a cultivation method of nastathium in which irradiation is performed at a ratio of ~ 1: 1 and cultivation is performed at a cultivation temperature of 20 to 25 ° C. under cultivation conditions for 10 to 30 days, and irradiation is performed with fluorescent light or sunlight having the same photosynthetic photon bundle density. However, a method for cultivating nastathium , which is characterized by having a higher antioxidant effect than nastatium cultivated under the same cultivation conditions . 請求項1に記載された栽培方法で栽培されたナスタチウムを、水、低級アルコール及び液状多価アルコールから選ばれる一種又は二種以上の溶媒によって抽出した抽出物を0.001〜10重量%含有することを特徴とするしわ形成抑制剤。 The Nasturtium grown in the described cultivation method in claim 1, water, the extract extracted by one or two or more solvents selected from lower alcohols and liquid polyhydric alcohols containing from 0.001 to 10 wt% A wrinkle formation inhibitor characterized by this. 請求項1に記載された栽培方法で栽培されたナスタチウムを、水、低級アルコール及び液状多価アルコールから選ばれる一種又は二種以上の溶媒によって抽出した抽出物を0.001〜10重量%含有することを特徴とする抗酸化剤。
The Nasturtium grown in the described cultivation method in claim 1, water, the extract extracted by one or two or more solvents selected from lower alcohols and liquid polyhydric alcohols containing from 0.001 to 10 wt% An antioxidant characterized by that.
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