JP2022022526A - External preparation and internal preparation for skin - Google Patents
External preparation and internal preparation for skin Download PDFInfo
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- JP2022022526A JP2022022526A JP2020109853A JP2020109853A JP2022022526A JP 2022022526 A JP2022022526 A JP 2022022526A JP 2020109853 A JP2020109853 A JP 2020109853A JP 2020109853 A JP2020109853 A JP 2020109853A JP 2022022526 A JP2022022526 A JP 2022022526A
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Abstract
Description
本発明は、ＭＭＰ阻害剤、コラ－ゲン産生促進剤、シワ改善剤、ヒアルロン酸産生促進剤、抗酸化剤、美白剤、医薬品及び食品組成物に関する。 The present invention relates to MMP inhibitors, collagen production promoters, wrinkle improvers, hyaluronic acid production promoters, antioxidants, whitening agents, pharmaceuticals and food compositions.
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シワがある。シワには、表皮性のシワと、真皮性のシワの二種類が存在することが知られている。表皮性のシワは小ジワと呼ばれ、皮膚の乾燥により、表皮角質中の水分量が低下することによって一時的に生じるシワである。一方、真皮性のシワは、太陽光線に含まれる紫外線や加齢によって形成されるシワである。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コラ－ゲンの合成能の低下や、マトリックスプロテア－ゼ（ＭＭＰ）の増加によるコラ－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, functional deterioration of the skin 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 epidermal keratin due to dry skin. On the other hand, dermal wrinkles are wrinkles formed by ultraviolet rays contained in the sun's rays and aging. The formation mechanism includes a decrease in collagen synthesis ability in dermal fibroblasts due to ultraviolet rays and aging, and an increase in matrix protease (MMP) to promote collagen degradation.
乾燥に起因する表皮性のシワと真皮性のシワでは、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シワは、保湿効果を有する化粧品の使用によって改善することは困難である。 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 are improved by using cosmetics having a moisturizing effect. That is difficult.
これまでに、紫外線によって生じる真皮性のシワを改善することを目的として、加水分解ア－モンドを有効成分とする皮膚のシワ形成防止・改善剤（特許文献１）、ジョチョウケイ、テンキシ及びキセンソウの抽出物を有効成分とする紫外線照射に起因するシワの改善剤（特許文献２）が報告されている。 So far, for the purpose of improving the dermal wrinkles caused by ultraviolet rays, a skin wrinkle formation preventing / improving agent containing hydrolyzed almond as an active ingredient (Patent Document 1), Jochokei, Tenki and Kisensou An agent for improving wrinkles caused by irradiation with ultraviolet rays containing an extract as an active ingredient (Patent Document 2) has been reported.
また、真皮には線維芽細胞やコラ－ゲンが存在し、Ｉ型コラ－ゲンが全体の８０％を占める。Ｉ型コラ－ゲンの他には、ＩＩＩ、Ｖ、ＸＩＩ及びＸＩＶ型コラ－ゲンの存在が知られている。シワやたるみの原因の一つとして、Ｉ型コラ－ゲンの減少が挙げられる。従って、Ｉ型コラ－ゲンの産生を促進させることがシワ・たるみの予防・改善に有効であると考えられる。また、Ｉ型コラ－ゲンの産生促進は皮膚の創傷治癒の改善にも有効である。 In addition, fibroblasts and collagen are present in the dermis, and type I collagen accounts for 80% of the total. In addition to type I collagen, the presence of type III, V, XII and XIV collagen is known. One of the causes of wrinkles and sagging is a decrease in type I collagen. Therefore, it is considered that promoting the production of type I collagen is effective in preventing and improving wrinkles and sagging. In addition, promotion of type I collagen production is also effective in improving skin wound healing.
また、コラ－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、及び皮膚等の、多くのマトリックス組織の必須な成分である。ＭＭＰに属するコラゲナ－ゼ（ＭＭＰ－１）により一箇所を切断されると、通常の組織内では安定なコラ－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－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 also a major structural protein that occupies about one-third of mammalian tissues and is an essential component of many matrix tissues such as cartilage, bone, tendons, and skin. When one site is cleaved by collagenase (MMP-1) belonging to MMP, stable collagen molecules 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－ゼ（ＭＭＰ－２）は、線維芽細胞や内皮細胞、癌細胞等が産生する酵素であり、コラ－ゲン、ゼラチン、エラスチン（動脈、健、皮膚等の弾性組織の特殊成分をなす構造タンパク質）等の基質を分解する。従って、ゼラチナ－ゼに対して阻害活性を有する物質は、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の阻害はガン疾患のみならず、潰瘍形成、慢性関節リウマチ、骨粗鬆症、歯周炎症、ＭＭＰの亢進が原因で起こる各種疾患の予防、治療及び改善に有用である。 Zeratinase (MMP-2), which belongs to MMP, is an enzyme produced by fibroblasts, endothelial cells, cancer cells, etc., and is a special component of collagen, gelatin, elastin (arteries, health, skin, and other elastic tissues). Degrades substrates such as structural proteins). Therefore, a substance having an inhibitory activity against zeratinase is expected to have an effect of suppressing angiogenesis and cancer metastasis in cancer tissues, and is considered to be useful for prevention and treatment of cancer diseases. Furthermore, inhibition of MMP is useful not only for cancer diseases but also for prevention, treatment and improvement of various diseases caused by ulcer formation, rheumatoid arthritis, osteoporosis, periodontal inflammation and increased MMP.
コラゲナ－ゼの阻害活性を有する素材として、例えば、カカオ豆皮であるカカオハスク抽出物（特許文献３）、バラ科オニイチゴ抽出物（特許文献４）、ラクトフェリン（特許文献５）等が提案されている。皮膚老化や口腔衛生にますます関心が高まっている状況下で、副作用がなく、安全性が高い、コラゲナ－ゼ活性阻害作用の優れた素材を見出すことが求められている。 As a material having an inhibitory activity on collagenase, for example, a cacao husk extract (Patent Document 3), a Rosaceae onistrawberry extract (Patent Document 4), and lactoferrin (Patent Document 5), which are cacao bean peels, have been proposed. .. Under the increasing interest in skin aging and oral hygiene, it is required to find a material having no side effects, high safety, and excellent topoisomerase activity inhibitory action.
また、線維芽細胞はコラ－ゲン等のタンパク質及びヒアルロン酸等のグリコサミノグリカンを産生して真皮結合組織を形成し、皮膚のハリを保っている。この結合組織が収縮力を失い、さらに弾力性を失う結果として皮膚のシワやたるみが発生すると考えられている。 In addition, fibroblasts produce proteins such as collagen and glycosaminoglycans such as hyaluronic acid to form dermal connective tissue and maintain the firmness of the skin. It is believed that this connective tissue loses contractile force and further loses elasticity, resulting in wrinkles and sagging of the skin.
特にヒアルロン酸は結合組織に広く分布する高分子多糖体として知られており、真皮中でゲル状の形態を呈し、肌の弾力を維持している。従って、ヒアルロン酸の変質や減少が皮膚老化において重要であると考えられている。また、ヒアルロン酸は高分子であるため、それを含有した化粧料を皮膚に直接塗布しても吸収されにくいという問題があった。そこで、これまで、線維芽細胞を活性化することで、細胞自らのコラ－ゲンやヒアルロン酸の産生を促進させることができる皮膚外用剤が模索されてきた（特許文献６）。また、ヒアルロン酸は、関節にも存在しており、関節の荷重の衝撃を和らげたり、関節の動きを滑らかにしたりする機能を果たしていることが知られている。変形性関節炎、慢性関節リウマチ、化膿性関節炎、痛風性関節炎、外傷性関節炎及び骨関節炎等の関節疾患の場合は、関節液中のヒアルロン酸量が低下したり、加齢によって低下したりすることが知られている。このような関節疾患において、潤滑機能の改善、関節軟骨の被覆や保護、痛みの抑制及び病的関節液の改善もしくは正常化のために、関節液中のヒアルロン酸量を増加させることが有効であると考えられる。例えば、慢性関節リウマチ、外傷性関節炎、骨関節炎及び変形性関節炎の患者にヒアルロン酸ナトリウムの関節注入法を行うと上記症状の改善が認められることが知られている。しかし、これらの治療は長期にわたる。従って、日常生活の中で手軽に予防や治療などができるように、ヒアルロン酸産生促進剤を含有させた食品や医薬品が望まれている。 In particular, hyaluronic acid is known as a high molecular weight polysaccharide widely distributed in connective tissue, exhibits a gel-like morphology in the dermis, and maintains the elasticity of the skin. Therefore, alteration or reduction of hyaluronic acid is considered to be important in skin aging. Further, since hyaluronic acid is a polymer, there is a problem that it is difficult to be absorbed even if a cosmetic containing it is directly applied to the skin. Therefore, so far, a skin external preparation capable of promoting the production of collagen and hyaluronic acid of the cells themselves by activating fibroblasts has been sought (Patent Document 6). Hyaluronic acid is also present in joints, and is known to play a function of cushioning the impact of joint loads and smoothing joint movements. In the case of joint diseases such as osteoarthritis, rheumatoid arthritis, purulent arthritis, gouty arthritis, traumatic arthritis and osteoarthritis, the amount of hyaluronic acid in the joint fluid decreases or decreases with age. It has been known. In such joint diseases, it is effective to increase the amount of hyaluronic acid in the synovial fluid for the purpose of improving the lubrication function, covering and protecting the articular cartilage, suppressing pain, and improving or normalizing the pathological synovial fluid. It is believed that there is. For example, it is known that joint injection of sodium hyaluronate is performed in patients with rheumatoid arthritis, traumatic arthritis, osteoarthritis and osteoarthritis to improve the above symptoms. However, these treatments are long-term. Therefore, foods and pharmaceuticals containing a hyaluronic acid production promoter are desired so that they can be easily prevented or treated in daily life.
飛蚊症とは、視界内に糸くずや蚊のように見える薄い影が現れる症状で、目の内部を満たす硝子体内の混濁が網膜上に影を落とすことで発生する。飛蚊症は大きく２種類に分けることができ、加齢や紫外線、活性酸素等の影響で発症する生理的飛蚊症と網膜剥離、網膜裂孔、硝子体出血、ぶどう膜炎等の疾患の一症状として現れる病的飛蚊症がある。生理的飛蚊症は、硝子体の主要成分であるヒアルロン酸の減少による液状化と、それに伴うコラ－ゲン線維の崩壊で硝子体内が混濁することで生じる。治療法として、硝子体切除手術やレ－ザ－治療があるが、これらの施術は安全性の観点から日本ではあまり行われていないという実情があり、外国で治療を行うには多額の費用が必要となる。そのため、生理的飛蚊症を予防改善するためには日常的に利用可能なヒアルロン酸産生促進剤を含有させた食品や医薬品が望まれている。 Floater is a condition in which a thin shadow that looks like lint or a mosquito appears in the field of vision, and is caused by the opacity in the vitreous that fills the inside of the eye and casts a shadow on the retina. Floater can be broadly divided into two types: physiological floater that develops due to the effects of aging, ultraviolet rays, active oxygen, etc., and one of the diseases such as retinal detachment, retinal detachment, vitreous hemorrhage, and uveitis. There is pathological floater that appears as a symptom. Physiological floater is caused by liquefaction due to a decrease in hyaluronic acid, which is a major component of the vitreous body, and concomitant disruption of collagen fibers, which causes the vitreous body to become opaque. There are vitrectomy surgery and laser treatment as treatment methods, but there is a fact that these treatments are not often performed in Japan from the viewpoint of safety, and it costs a lot of money to perform treatment in a foreign country. You will need it. Therefore, in order to prevent and improve physiological floater, foods and pharmaceuticals containing a hyaluronic acid production promoter that can be used on a daily basis are desired.
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ニン色素生成細胞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、内用や外用等において、アスコルビン酸（ビタミンＣ）等が用いられてきた（特許文献７）。 In general, skin pigmentation seen in age spots, freckles, sunburns, etc. is caused by melanin pigmentation cells existing in the skin excessively producing melanin pigment due to hormonal abnormalities or UV stimulation, which are deposited in the skin. Is believed to be the cause. 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 (Patent Document 7).
また、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共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が進行すると考えられる。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、ガンや心筋梗塞等様々な生活習慣病が発症したりすると考えられる。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－ゼ等の活性酸素消去酵素、ＳＯＤ様活性物質等の活性酸素消去剤や抗酸化剤を含有した食品、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８、９）。 In addition, the skin is located in the outermost layer of the living body, and is an organ in which active oxygen is easily generated 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 enzymes in skin cells decreases with aging, and when the damage caused by active oxygen exceeds the protective reaction, the skin is oxidized and the cell function deteriorates and aging. Is expected to progress. 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 have been studied. Foods, cosmetics, non-pharmaceutical products, pharmaceuticals and the like containing the above have been developed (Patent Documents 8 and 9).
バラ目バラ科ナナカマド属のセイヨウナナカマド（学名 Ｓｏｒｂｕｓ ａｕｃｕｐａｒｉａ）は、その植物油や果実の発酵液が毛髪やネイルのコンディショニング剤に適用されること（特許文献１０、１１）が知られている。しかしながら、セイヨウナナカマドの果実が、ＭＭＰ阻害作用、コラ－ゲン産生促進作用、ヒアルロン酸産生促進作用、抗酸化作用及びメラニン生成抑制作用を有することは知られていなかった。 It is known that the rowan rowan genus Rowan (scientific name: Sorbus aucuparia) is applied to a conditioning agent for hair and nails by applying a fermented liquid of vegetable oil or fruit (Patent Documents 10 and 11). However, it has not been known that the fruit of rowan has an MMP inhibitory effect, a collagen production promoting effect, a hyaluronic acid production promoting effect, an antioxidant effect, and a melanin production inhibitory effect.
安全で安定性に優れ、ＭＭＰ阻害作用、コラ－ゲン産生促進作用、ヒアルロン酸産生促進作用、抗酸化作用及びメラニン生成抑制作用に優れた素材が望まれているが、未だ十分満足し得るものが提供されていないのが現状である。 Materials that are safe, have excellent stability, and have excellent MMP inhibitory action, collagen production promoting action, hyaluronic acid production promoting action, antioxidant action, and melanin production inhibitory action are desired, but those that are still sufficiently satisfactory are desired. Currently, it is not provided.
本発明者らは、この課題を解決すべく、鋭意検討した結果、セイヨウナナカマドの果実抽出物が優れたＭＭＰ阻害作用、コラ－ゲン産生促進作用、ヒアルロン酸産生促進作用、抗酸化作用及びメラニン生成抑制作用を持ち、安定性においても優れていることを見出した。さらに、その抽出物を含有する外用剤又は内用剤が、安全で安定であり、ＭＭＰ阻害作用、コラ－ゲン産生促進作用、ヒアルロン酸産生促進作用、抗酸化作用及びメラニン生成抑制作用に優れており、多機能性美容・健康用素材・医薬品と成り得ることを見出し、本発明を完成するに至った。 As a result of diligent studies to solve this problem, the present inventors have found that rowan rowan fruit extract has excellent MMP inhibitory action, collagen production promoting action, hyaluronic acid production promoting action, antioxidant action and melanin production. It was found that it has an inhibitory effect and is also excellent in stability. Furthermore, the external or internal preparation containing the extract is safe and stable, and is excellent in MMP inhibitory action, collagen production promoting action, hyaluronic acid production promoting action, antioxidant action and melanin production suppressing action. We have found that it can be a multifunctional beauty / health material / pharmaceutical product, and have completed the present invention.
すなわち、本発明は、以下の（１）～（８）からなる。 That is, the present invention comprises the following (1) to (8).
（１）セイヨウナナカマドの果実の抽出物を含有することを特徴とするＭＭＰ阻害剤。
（２）セイヨウナナカマドの果実の抽出物を含有することを特徴とするコラ－ゲン産生促進剤。
（３）セイヨウナナカマドの果実の抽出物を含有することを特徴とするシワ改善剤。
（４）セイヨウナナカマドの果実の抽出物を含有することを特徴とするヒアルロン酸産生促進剤。
（５）セイヨウナナカマドの果実の抽出物を含有することを特徴とする抗酸化剤。
（６）セイヨウナナカマドの果実の抽出物を含有することを特徴とする美白剤。
（７）セイヨウナナカマドの果実の抽出物を含有することを特徴とする医薬品。
（８）セイヨウナナカマドの果実の抽出物を含有することを特徴とするＭＭＰの亢進が原因で起こる各種疾患、関節疾患及び生理的飛蚊症の予防改善用食品組成物。
(1) An MMP inhibitor characterized by containing an extract of rowan fruit.
(2) A collagen production promoter characterized by containing an extract of rowan fruit.
(3) A wrinkle improving agent containing an extract of rowan fruit.
(4) A hyaluronic acid production promoter containing an extract of rowan fruit.
(5) An antioxidant characterized by containing an extract of rowan fruit.
(6) A whitening agent containing an extract of rowan fruit.
(7) A pharmaceutical product containing an extract of rowan fruit.
(8) A food composition for preventing and improving various diseases, joint diseases and physiological floater caused by an increase in MMP, which comprises an extract of rowan fruit.
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.
本発明に用いるセイヨウナナカマド（学名 Ｓｏｒｂｕｓ ａｕｃｕｐａｒｉａ）は、バラ目バラ科ナナカマド属に属するヨ－ロッパ原産の落葉樹であり、８～１０メ－トル程度の中低木である。果実はナシ状果で、夏季になるにつれて成熟すると緑色から鮮やかな赤色となり、主に食用として用いられている。 Rowan (scientific name: Rowan aucuparia) used in the present invention is a deciduous tree native to Europe belonging to the genus Rowan of the Rosales family, and is a medium-sized shrub of about 8 to 10 meters. The fruits are pome-like fruits, which change from green to bright red as they mature in the summer, and are mainly used for food.
本発明に用いるセイヨウナナカマドの果実は、生育地域から入手することもできるし、市販品を購入することもできる。また、抽出には果実本体をそのまま抽出してもよく、乾燥、粉砕、細切等の処理を行ってもよい。 The fruit of rowan used in the present invention can be obtained from the growing area or can be purchased as a commercial product. Further, the fruit itself may be extracted as it is, or may be dried, crushed, shredded or the like.
抽出溶媒としては、例えば、水、低級アルコ－ル類（メタノ－ル、エタノ－ル、１－プロパノ－ル、２－プロパノ－ル、１－ブタノ－ル、２－ブタノ－ル等）、液状多価アルコ－ル類（１，３－ブチレングリコ－ル、プロピレングリコ－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－テル類（エチルエ－テル、テトラヒドロフラン、プロピルエ－テル等）が挙げられる。好ましくは、水、低級アルコ－ル及び液状多価アルコ－ル等の極性溶媒が良く、特に好ましくは、水、エタノ－ル、１，３－ブチレングリコ－ル及びプロピレングリコ－ルがよい。これらの溶媒は一種でも二種以上を混合して用いてもよい。特に好ましい抽出溶媒としては、水、エタノ－ル、１，３－ブチレングリコ－ル、水－エタノ－ル系の混合極性溶媒、または水－１，３－ブチレングリコ－ル系の混合極性溶媒が挙げられる。溶媒の使用量については、特に限定はなく、例えばセイヨウナナカマドの果実（乾燥重量）に対し、１０倍以上、好ましくは２０倍以上であればよいが、抽出後に濃縮を行ったり、単離したりする場合の操作の便宜上１００倍以下であることが好ましい。また、抽出温度や時間は、用いる溶媒の種類や抽出時の圧力等によって適宜選択できる。 Examples of the extraction solvent include water, lower alcohols (methanol, ester, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), and liquid. Polyvalent 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 alcohol and liquid polyvalent alcohol are preferred, and water, ethanol, 1,3-butylene glycol and propylene glycol are particularly preferred. These solvents may be used alone or in admixture of two or more. Particularly preferred extraction solvents include water, ethanol, 1,3-butylene glycol, a water-ethanol mixed polar solvent, or a water-1,3-butylene glycol mixed polar solvent. Can be mentioned. The amount of the solvent used is not particularly limited, and may be, for example, 10 times or more, preferably 20 times or more the amount of the fruit (dry weight) of rowan, but may be concentrated or isolated after extraction. It is preferably 100 times or less for convenience of operation in the case. The extraction temperature and time can be appropriately selected depending on the type of solvent used, the pressure at the time of extraction, and the like.
その抽出方法は特に限定されず、加熱抽出、常温抽出、低温抽出、攪拌抽出またはカラム抽出する方法等により行うことができる。また、その抽出物と果実を併用することもできる。 The extraction method is not particularly limited, and can be performed by a method such as heat extraction, room temperature extraction, low temperature extraction, stirring extraction, or column extraction. Moreover, the extract and the fruit can also be used together.
上記抽出物は、抽出した溶液のまま用いてもよいが、必要に応じて、本発明の効果を奏する範囲で、濃縮（減圧濃縮、膜濃縮等による濃縮）、希釈、濾過、活性炭等による脱色、脱臭、エタノ－ル沈殿等の処理を行ってから用いてもよい。さらには、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よい。 The above extract may be used as it is in the extracted solution, but if necessary, concentration (concentration by vacuum concentration, membrane concentration, etc.), dilution, filtration, decolorization by activated carbon, etc. is performed within the range in which the effect of the present invention is exhibited. , Deodorization, ethanol precipitation, etc. may be performed before use. Further, the extracted solution may be subjected to treatments such as concentrated drying, spray drying, freeze-drying and the like, and used as a dried product.
本発明は、上記抽出物をそのまま使用しても良く、抽出物の効果を損なわない範囲内で、化粧品、医薬部外品、医薬品又は食品等に用いられる成分である油脂類、ロウ類、炭化水素類、脂肪酸類、アルコ－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－ト剤、賦形剤、皮膜剤、甘味料、酸味料等の成分が含有されていてもよい。 In the present invention, the above-mentioned extract may be used as it is, and as long as the effect of the extract is not impaired, fats and oils, waxes and charcoal which are components used in cosmetics, non-pharmaceutical products, pharmaceuticals or foods, etc. Hydrogens, fatty acids, alcohols, esters, surfactants, metal soaps, pH regulators, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments, antioxidants, Ingredients such as whitening agents, killer agents, excipients, film agents, sweeteners and acidulants may be contained.
本発明は、化粧品、医薬部外品、医薬品、食品のいずれにも用いることができ、その剤形としては、例えば、化粧水、クリ－ム、乳液、ゲル剤、エアゾ－ル剤、エッセンス、パック、洗浄剤、浴用剤、ファンデ－ション、打粉、口紅、軟膏、パップ剤、錠菓、カプセル剤、チョコレ－ト、ガム、飴、飲料、散剤、顆粒剤、錠剤、糖衣錠剤、カプセル剤、シロップ剤、丸剤、懸濁剤、液剤、乳剤、坐剤、注射用溶液等が挙げられる。 The present invention can be used in any of cosmetics, non-pharmaceutical products, pharmaceuticals, and foods, and the dosage forms thereof include, for example, cosmetics, creams, emulsions, gels, air pills, essences, and the like. Packs, cleaning agents, bathing agents, foundations, dusting powders, lipsticks, ointments, poultices, tablets, capsules, chocolates, gums, candy, beverages, powders, granules, tablets, sugar-coated tablets, capsules, Examples include syrups, pills, capsules, solutions, emulsions, suppositories, injection solutions and the like.
外用の場合、本発明に用いる上記抽出物の含有量は、固形物に換算して０．０００１重量％以上が好ましく、０．００１～１０重量％がより好ましい。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％を越えると、効果の増強は認められにくく不経済である。 In the case of external use, the content of the extract used in the present invention is preferably 0.0001% by weight or more, more preferably 0.001 to 10% by weight in terms of solid matter. Further, 0.01 to 5% by weight is most preferable. If it is less than 0.0001% by weight, it is difficult to expect a sufficient effect. If it exceeds 10% by weight, the enhancement of the effect is hardly recognized and it is uneconomical.
内用の場合、摂取量は年齢、体重、症状、治療効果、投与方法、処理時間等により異なる。通常、成人１人当たりの１日の摂取量としては、５ｍｇ以上が好ましく、１０ｍｇ～５ｇがより好ましい。さらに、２０ｍｇ～２ｇが最も好ましい。 For internal use, the intake varies depending on age, body weight, symptoms, therapeutic effect, administration method, treatment time, and the like. Usually, the daily intake per adult is preferably 5 mg or more, more preferably 10 mg to 5 g. Further, 20 mg to 2 g is most preferable.
次に本発明を詳細に説明するため、実施例として本発明に用いる抽出物の製造例、実験例及び処方例を挙げるが、本発明はこれに限定されるものではない。製造例に示す％とは重量％を、処方例に示す含有量の部とは重量部を示す。 Next, in order to explain the present invention in detail, production examples, experimental examples, and formulation examples of the extract used in the present invention will be given as examples, but the present invention is not limited thereto. The% shown in the production example means% by weight, and the content part shown in the formulation example means a weight part.
セイヨウナナカマドの果実抽出物の製造例
セイヨウナナカマドの果実抽出物を以下のとおり製造した。製造例１～４において抽出材料にはセイヨウナナカマドの果実を用いた。
Example of Production of Rowan Fruit Extract The fruit extract of rowan was produced as follows. In Production Examples 1 to 4, the fruit of rowan was used as the extraction material.
（製造例１）セイヨウナナカマド果実の熱水抽出物の調製
セイヨウナナカマドの果実の乾燥物１０ｇに２００ｍＬの水を加え、９５～１００℃で２時間抽出した。得られた抽出液を濾過し、その濾液を濃縮し、凍結乾燥してセイヨウナナカマドの果実の熱水抽出物を３．６ｇ得た。
(Production Example 1) Preparation of hot water extract of rowan fruit 200 mL of water was added to 10 g of dried rowan fruit and extracted at 95-100 ° C. for 2 hours. The obtained extract was filtered, the filtrate was concentrated, and freeze-dried to obtain 3.6 g of a hot water extract of rowan fruit.
（製造例２）セイヨウナナカマドの果実の５０％エタノ－ル抽出物の調製
セイヨウナナカマドの果実の乾燥物１０ｇを２００ｍＬの５０％エタノ－ル水溶液に室温で７日間浸漬し抽出を行った。得られた抽出液を濾過した後、エバポレ－タ－で濃縮乾固してセイヨウナナカマドの果実の５０％エタノ－ル抽出物を３．５ｇ得た。
(Production Example 2) Preparation of 50% Ethanol Extract of Rowan Fruit 10 g of dried rowan fruit was immersed in 200 mL of 50% ethanol aqueous solution at room temperature for 7 days for extraction. The obtained extract was filtered and then concentrated to dryness with an evaporator to obtain 3.5 g of 50% rowan extract of rowan fruit.
（製造例３）セイヨウナナカマドの果実のエタノ－ル抽出物の調製
セイヨウナナカマドの果実の乾燥物１０ｇを２００ｍＬのエタノ－ルに室温で７日間浸漬し抽出を行った。得られた抽出液を濾過した後、エバポレ－タ－で濃縮乾固してセイヨウナナカマドの果実のエタノ－ル抽出物を３．３ｇ得た。
(Production Example 3) Preparation of Rowan Fruit Ethanol Extract 10 g of dried rowan fruit was immersed in 200 mL rowan at room temperature for 7 days for extraction. After filtering the obtained extract, it was concentrated to dryness with an evaporator to obtain 3.3 g of an ethanol extract of rowan fruit.
（製造例４）セイヨウナナカマドの果実の１，３－ブチレングリコ－ル抽出物の調製
セイヨウナナカマドの果実の乾燥物１０ｇを２００ｍＬの１，３－ブチレングリコ－ルに低温で７日間浸漬し抽出を行った。得られた抽出液を濾過してセイヨウナナカマドの果実の１，３－ブチレングリコ－ル抽出物を１９２ｇ得た。
(Production Example 4) Preparation of 1,3-butylene glycol extract of rowan fruit Soak 10 g of dried rowan fruit in 200 mL of 1,3-butylene glycol at low temperature for 7 days for extraction. went. The obtained extract was filtered to obtain 192 g of 1,3-butylene glycol extract of rowan fruit.
次に、本発明の効果を詳細に説明するため、実験例を挙げる。 Next, in order to explain the effect of the present invention in detail, an experimental example will be given.
実験例１ Ｉ型コラ－ゲン（ＣＯＬ１Ａ１）、ヒアルロン酸合成酵素２（ＨＡＳ２）、ＭＭＰ－１及びＭＭＰ－２ ｍＲＮＡ発現量の測定
ヒト皮膚線維芽細胞（もしくはケラチノサイト）を６０ｍｍ ｄｉｓｈに１×１０５個播種し、１０％ＦＢＳを含むＤＭＥＭ培養液にて、３７℃、５％ＣＯ２条件下で培養した。コンフルエントな状態になったところで、各試料を最終濃度１、１０もしくは１００μｇ／ｍＬとなるように添加した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ＲＮＡｉｓｏ Ｐｌｕｓ（タカラバイオ）を用いて行い、総ＲＮＡ量は分光光度計（ＮａｎｏＤｒｏｐ）を用いて２６０ｎｍにおける吸光度により求めた。ｍＲＮＡ発現量の測定は、細胞から抽出した総ＲＮＡを基にしてリアルタイムＲＴ－ＰＣＲ法により行った。リアルタイムＲＴ－ＰＣＲ法には、Ｈｉｇｈ Ｃａｐａｃｉｔｙ ＲＮＡ－ｔｏ－ｃＤＮＡ Ｋｉｔ（Ａｐｐｌｉｅｄ Ｂｉｏｓｙｓｔｅｍｓ）及びＳＹＢＲ Ｓｅｌｅｃｔ Ｍａｓｔｅｒ Ｍｉｘ（Ａｐｐｌｉｅｄ Ｂｉｏｓｙｓｔｅｍｓ）を用いた。即ち、５００ｎｇの総ＲＮＡを逆転写反応後、ＰＣＲ反応（９５℃：１５秒間、６０℃：６０秒間、４０ｃｙｃｌｅｓ）を行った。その他の操作は定められた方法に従い、ＣＯＬ１Ａ１、ＨＡＳ２、ＭＭＰ－１及びＭＭＰ－２ ｍＲＮＡの発現量を、内部標準であるＧＡＰＤＨ ｍＲＮＡの発現量に対する割合として求めた。ＣＯＬ１Ａ１発現率は、コントロール（試料未添加）群のＣＯＬ１Ａ１ ｍＲＮＡの発現量に対する試料添加群のＣＯＬ１Ａ１ ｍＲＮＡの発現量の比率として算出した。ＨＡＳ２、ＭＭＰ－１及びＭＭＰ－２発現率についても、同様に算出した。尚、各遺伝子の発現量の測定に使用したプライマーは次の通りである。
Experimental Example 1 Measurement of expression levels of type I collagen (COL1A1), hyaluronan synthase 2 (HAS2), MMP-1 and MMP-2 mRNA expression Human skin fibroblasts (or keratinocytes) 1 × 10 5 in 60 mm dish Individuals were sown and cultured in DMEM culture medium containing 10% FBS under 37 ° C. and 5% CO 2 conditions. When the sample was in a confluent state, each sample was cultured in DMEM (-) culture medium added to a final concentration of 1, 10 or 100 μg / mL for 24 hours, and then total RNA was extracted. Extraction of total RNA from cells was performed using RNAiso Plus (Takara Bio), and the total amount of RNA was determined by absorbance at 260 nm using a spectrophotometer (NanoDrop). The mRNA expression level was measured by the real-time RT-PCR method based on the total RNA extracted from the cells. For the real-time RT-PCR method, High Capacity RNA-to- cDNA Kit (Applied Biosystems) and SYBR Select Master Mix (Applied Biosystems) were used. That is, after a reverse transcription reaction of 500 ng of total RNA, a PCR reaction (95 ° C: 15 seconds, 60 ° C: 60 seconds, 40 cycles) was performed. For other operations, the expression levels of COL1A1, HAS2, MMP-1 and MMP-2 mRNA were determined as a ratio to the expression level of GAPDH mRNA, which is an internal standard, according to a predetermined method. The COL1A1 expression rate was calculated as the ratio of the expression level of COL1A1 mRNA in the sample-added group to the expression level of COL1A1 mRNA in the control (non-sampled) group. The expression rates of HAS2, MMP-1 and MMP-2 were also calculated in the same manner. The primers used to measure the expression level of each gene are as follows.
ＣＯＬ１Ａ１用のプライマ－セット
ＡＧＧＡＣＡＡＧＡＧＧＣＡＴＧＴＣＴＧＧＴＴ（配列番号１）
ＴＴＧＣＡＧＴＧＧＴＡＧＧＴＧＡＴＧＴＴＣＴＧ（配列番号２）
ＨＡＳ２用のプライマ－セット
ＴＧＧＡＴＧＡＣＣＴＡＣＧＡＡＧＣＧＡＴＴＡ（配列番号３）
ＧＣＴＧＧＡＴＴＡＣＴＧＴＧＧＣＡＡＴＧＡＧ（配列番号４）
ＭＭＰ－１用のプライマ－セット
ＧＧＧＡＧＡＴＣＡＴＣＧＧＧＡＣＡＡＣＴＣ（配列番号５）
ＴＧＡＧＣＡＴＣＣＣＣＴＣＣＡＡＴＡＣＣ（配列番号６）
ＭＭＰ－２用のプライマ－セット
ＣＣＧＴＣＧＣＣＣＡＴＣＡＴＣＡＡ（配列番号７）
ＣＴＴＣＴＧＣＡＴＣＴＴＣＴＴＴＡＧＴＧＴＧＴＣＣＴＴ（配列番号８）
ＧＡＰＤＨ用のプライマ－セット
ＣＡＣＴＣＴＴＣＣＡＧＣＣＴＴＣＣＴＴＣＣ（配列番号９）
ＧＴＧＴＴＧＧＣＧＴＡＣＡＧＧＴＣＴＴＴＧ（配列番号１０）
Primer set for COL1A1 AGGACAAGAGGCATGTCGGTT (SEQ ID NO: 1)
TTGCAGTGGTAGGTGATGTTCG (SEQ ID NO: 2)
Primer set for HAS2 TGGATGACCTACGAAGCGATTA (SEQ ID NO: 3)
GCTGGATTACTGTGGCAATGAG (SEQ ID NO: 4)
Primer set for MMP-1 GGGAGATACCATCGGGGACAACTC (SEQ ID NO: 5)
TGAGCATCCCCTCCAATACC (SEQ ID NO: 6)
Primer set for MMP-2 CCGTCGCCCATCATCAA (SEQ ID NO: 7)
CTTTGCATCTTCTTTAGTGTGTCCTT (SEQ ID NO: 8)
Primer set for GAPDH CACTTTCCAGCCTTCCTTCC (SEQ ID NO: 9)
GTGTTGGGCGTACAGGTCTTG (SEQ ID NO: 10)
これらの実験結果を表１～４に示した。その結果、本発明のセイヨウナナカマドの果実抽出物には、優れたＣＯＬ１Ａ１発現促進効果（コラ－ゲン産生促進効果）、ＨＡＳ２発現促進効果（ヒアルロン酸産生促進効果）、ＭＭＰ－１発現抑制効果（ＭＭＰ阻害効果）及びＭＭＰ－２発現抑制効果（ＭＭＰ阻害効果）が認められた。特に、セイヨウナナカマドの果実の熱水抽出物（製造例１）のＣＯＬ１Ａ１発現促進及びＭＭＰ－１発現抑制、５０％エタノ－ル抽出物（製造例２）のＭＭＰ－２発現抑制、エタノ－ル抽出物（製造例３）のＣＯＬ１Ａ１発現促進及びＨＡＳ２発現促進において顕著に効果が高かった。 The results of these experiments are shown in Tables 1 to 4. As a result, the fruit extract of Rowan of the present invention has an excellent COL1A1 expression promoting effect (collagen production promoting effect), HAS2 expression promoting effect (hyaluronic acid production promoting effect), and MMP-1 expression suppressing effect (MMP). Inhibitory effect) and MMP-2 expression inhibitory effect (MMP inhibitory effect) were observed. In particular, promotion of COL1A1 expression and suppression of MMP-1 expression in the hot water extract of rowan fruit (Production Example 1), suppression of MMP-2 expression in 50% ethanol extract (Production Example 2), and ethanol extraction. The effect was remarkably high in the promotion of COL1A1 expression and the promotion of HAS2 expression of the product (Production Example 3).
実験例２ Ｂ１６マウスメラノ－マを用いたメラニン生成抑制試験
Ｂ１６マウスメラノ－マを６０ｍｍ ｄｉｓｈに３×１０４個播種し、各試料を最終濃度１０μｇ／ｍＬ）となるように添加した１０％ＦＢＳを含むＭＥＭ培養液にて、３７℃、５％ＣＯ２条件下にて５日間培養した。培養後、細胞の剥離を行い、遠心分離をして得られたペレットを超音波破砕操作によりＰＢＳ（－）に溶解させた。タンパク質定量は、Ｌｏｗｒｙ法（Ｊ．Ｂｉｏｌ．Ｃｈｅｍ．，１９３，２６５－２７５，１９５１）を用いて行った。また、メラニン量を測定する場合、タンパク質定量用に取った残りの細胞破砕溶液に４Ｎ ＮａＯＨを加え、６０℃にて２時間加温した後、分光光度計（島津製作所）を用いて４７５ｎｍの吸光度を測定し、検量線からメラニン量を求め、１ｍｇタンパク質量あたりのメラニン量を算出した。メラニン生成抑制率は、コントロ－ル（試料未添加）群に対する試料添加群のメラニン量の減少量の割合から算出した。
Experimental Example 2 Test for suppressing melanin production using B16 mouse melanoma 10% FBS in which 3 × 10 4 B16 mouse melanoma were seeded in a 60 mm dish and each sample was added to a final concentration of 10 μg / mL). The cells were cultured in a MEM culture solution containing the above for 5 days under the conditions of 37 ° C. and 5% CO 2 . After culturing, the cells were detached, and the pellet obtained by centrifugation was dissolved in PBS (-) by an ultrasonic crushing operation. Protein quantification was performed using the Lowry method (J. Biol. Chem., 193,265-275,1951). When measuring the amount of melanin, add 4N NaOH to the remaining cell disruption solution taken for protein quantification, heat at 60 ° C for 2 hours, and then use a spectrophotometer (Shimadzu Seisakusho) to absorb 475 nm. Was measured, the amount of melanin was determined from the calibration curve, and the amount of melanin per 1 mg protein amount was calculated. The melanin production inhibition rate was calculated from the ratio of the decrease in the amount of melanin in the sample-added group to the control (sample-free) group.
これらの試験結果を表５に示した。本発明のセイヨウナナカマドの果実の熱水抽出物（製造例１）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。 The results of these tests are shown in Table 5. It was found that the hot water extract of the fruit of rowan of the present invention (Production Example 1) had an excellent melanin production inhibitory effect.
実験例３ 活性酸素消去試験（抗酸化試験）
フリ－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－ラジカルのモデルとしては、安定なフリ－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 3 Active oxygen scavenging test (antioxidant test)
The free radical scavenging and removing action was evaluated. Ascorbic acid was used as a positive control. As a free radical model, α, α-diphenyl-β-picrylhydrazyl (hereinafter referred to as DPPH), which is a stable free radical, is used, and the radical is reduced by reacting with the 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－ラジカル捕捉除去作用の測定方法
各試料を、終濃度１００μｇ／ｍＬ（アスコルビン酸は２０μｇ／ｍＬ）となるように加えた１．０Ｍ酢酸緩衝液（ｐＨ５．５）２ｍＬに無水エタノ－ル２ｍＬ及び０．５ｍＭ ＤＰＰＨ無水エタノ－ル溶液１ｍＬを加えて反応液とした。また、油溶性の試料の場合は無水エタノ－ル２ｍＬに試料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（Ａ）を測定した。また、ブランクとして試料の代わりに精製水を用いて吸光度（Ｂ）を測定した。フリ－ラジカル捕捉除去率は、以下に示す式より算出した。
フリ－ラジカル捕捉除去率（％）＝（１－Ａ／Ｂ）×１００
Measurement method of free radical scavenging and removal action 2 mL of anhydrous etanol was added to 2 mL of 1.0 M acetate buffer (pH 5.5) to which each sample was added so as to have a final concentration of 100 μg / mL (ascorbic acid is 20 μg / mL). And 1 mL of 0.5 mM DPPH anhydrous ethanol solution was added to prepare a reaction solution. In the case of an oil-soluble sample, the sample was added to 2 mL of anhydrous ethanol to prepare a reaction solution. Then, the reaction was carried out at 37 ° C. for 30 minutes, and the absorbance (A) at a wavelength of 517 nm was measured using water as a control. In addition, the absorbance (B) was measured using purified water instead of the sample as a blank. The free radical scavenger removal rate was calculated from the formula shown below.
Free radical scavenger removal rate (%) = (1-A / B) x 100
これらの試験結果を表６に示した。本発明のセイヨウナナカマドの果実の熱水抽出物（製造例１）及び５０％エタノ－ル抽出物（製造例２）は、安定で優れたフリ－ラジカル捕捉除去作用を有していることが認められた。 The results of these tests are shown in Table 6. It was found that the hot water extract (Production Example 1) and the 50% ethanol extract (Production Example 2) of the fruit of rowan of the present invention have a stable and excellent free radical scavenging and removing action. Was done.
（処方例１） 化粧水
処方 含有量（％）
１．セイヨウナナカマドの果実の熱水抽出物（製造例１） ２．０
２．１，３－ブチレングリコ－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－ル ５．０
８．パラオキシ安息香酸メチル ０．１
９．ポリオキシエチレン硬化ヒマシ油（４０Ｅ．Ｏ．） ０．１
１０．香料 適量
１１．精製水にて全量を１００とする
［製造方法］成分１～６及び１１と、成分７～１０をそれぞれ均一に溶解し、両者を混合し濾過して製品とする。
(Prescription example 1) Toner prescription content (%)
1. 1. Hot water extract of rowan fruit (Production Example 1) 2.0
2.1,3-butylene glycol 8.0
3. 3. Glycerin 2.0
4. Xanthan gum 0.02
5. Citric acid 0.01
6. Sodium citrate 0.1
7. Ethanol 5.0
8. Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40EO) 0.1
10. Appropriate amount of fragrance 11. [Manufacturing method] Ingredients 1 to 6 and 11 and components 7 to 10 are uniformly dissolved in purified water to make the total amount 100, and both are mixed and filtered to obtain a product.
（比較処方例１） 従来の化粧水
処方例１において、セイヨウナナカマドの果実の熱水抽出物を精製水に置き換えたものを、従来の化粧水とした。
(Comparative Prescription Example 1) Conventional Toner In Formulation Example 1, the hot water extract of rowan fruit was replaced with purified water, and the conventional lotion was used.
（処方例２） クリ－ム
処方 含有量（％）
１．セイヨウナナカマドの果実の５０％エタノ－ル抽出物（製造例２）１．０
２．スクワラン ５．５
３．オリ－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－テル（２０Ｅ．Ｏ．） ３．０
８．ベヘニルアルコ－ル １．５
９．モノステアリン酸グリセリン ２．５
１０．香料 ０．１
１１．パラオキシ安息香酸メチル ０．２
１２．１，３－ブチレングリコ－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、さらに３０℃まで冷却して製品とする。
(Prescription example 2) Cream prescription content (%)
1. 1. 50% rowan extract of rowan fruit (Production Example 2) 1.0
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. Behenil alcohol 1.5
9. Glycerin monostearate 2.5
10. Fragrance 0.1
11. Methyl paraoxybenzoate 0.2
12.1,3-butylene glycol 8.5
13. [Manufacturing method] Ingredients 2 to 9 having a total amount of 100 in purified water are heated and dissolved and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1 and 11 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, the component 10 is added at 45 ° C, and the product is further cooled to 30 ° C to obtain a product.
（比較処方例２） 従来のクリ－ム
処方例２において、セイヨウナナカマドの果実の５０％エタノ－ル抽出物を精製水に置き換えたものを、従来のクリ－ムとした。
(Comparative Prescription Example 2) Conventional Cream In Prescription Example 2, 50% ethanol extract of rowan fruit was replaced with purified water, and the conventional cream was used.
（処方例３） 乳液
処方 含有量（％）
１．セイヨウナナカマドの果実のエタノ－ル抽出物（製造例３） ０．０１
２．スクワラン ５．０
３．オリ－ブ油 ５．０
４．ホホバ油 ５．０
５．セタノ－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－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－ト（２０Ｅ．Ｏ．） ２．０
９．香料 ０．１
１０．プロピレングリコ－ル １．０
１１．グリセリン ２．０
１２．パラオキシ安息香酸メチル ０．２
１３．精製水にて全量を１００とする
［製造方法］成分１～８を加熱溶解して混合し、７０℃に保ち油相とする。成分１０～１３を加熱溶解して混合し、７５℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら冷却し、４５℃で成分９を加え、さらに３０℃まで冷却して製品とする。
(Prescription example 3) Emulsion prescription content (%)
1. 1. Ethanol extract of rowan fruit (Production Example 3) 0.01
2. 2. Squalene 5.0
3. 3. Olive oil 5.0
4. Jojoba oil 5.0
5. Setanol 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 Glico 1.0
11. Glycerin 2.0
12. Methyl paraoxybenzoate 0.2
13. [Manufacturing method] Ingredients 1 to 8 having a total amount of 100 in purified water are heated and dissolved and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 10 to 13 are heated and dissolved, mixed, and kept at 75 ° C. to prepare an aqueous phase. An aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring, component 9 is added at 45 ° C, and the product is further cooled to 30 ° C to obtain a product.
（処方例４） ゲル剤
処方 含有量（％）
１．セイヨウナナカマドの果実の
１，３－ブチレングリコ－ル抽出物（製造例４） １．０
２．エタノ－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－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－ ０．２
１０．水酸化カリウム ０．２
１１．精製水にて全量を１００とする
［製造方法］成分２～５と、成分１及び６～１１をそれぞれ均一に溶解し、両者を混合して製品とする。
(Prescription example 4) Gel preparation Prescription content (%)
1. 1. Rowan rowan fruit 1,3-butylene glycol extract (Production Example 4) 1.0
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５） パック
処方 含有量（％）
１．セイヨウナナカマドの果実の熱水抽出物（製造例１） １．０
２．セイヨウナナカマドの果実の
１，３－ブチレングリコ－ル抽出物（製造例４） ５．０
３．ポリビニルアルコ－ル １２．０
４．エタノ－ル ５．０
５．１，３－ブチレングリコ－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 5) Pack prescription content (%)
1. 1. Hot water extract of rowan fruit (Production Example 1) 1.0
2. 2. Rowan rowan fruit 1,3-butylene glycol extract (Production Example 4) 5.0
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 in purified water are uniformly dissolved to prepare a product.
（処方例６） ファンデ－ション
処方 含有量（％）
１．セイヨウナナカマドの果実の５０％エタノ－ル抽出物（製造例２）１．０
２．ステアリン酸 ２．４
３．ポリオキシエチレンソルビタンモノステアレ－ト（２０Ｅ．Ｏ．）１．０
４．ポリオキシエチレンセチルエ－テル（２０Ｅ．Ｏ．） ２．０
５．セタノ－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－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－ル ４．０
１２．トリエタノ－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－で撹拌し７５℃に保ち水相とする。油相に水相をかき混ぜながら加え、乳化する。その後、冷却し、４５℃で成分１８を加え、かき混ぜながら３０℃まで冷却して製品とする。
(Prescription example 6) Foundation prescription content (%)
1. 1. 50% rowan extract of rowan fruit (Production Example 2) 1.0
2. 2. Stearic acid 2.4
3. 3. Polyoxyethylene sorbitan monostelate (20EO) 1.0
4. Polyoxyethylene cetyl ether (20EO) 2.0
5. Setanol 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. Propene Glico 4.0
12. Trietanolamine 1.1
13. Methyl paraoxybenzoate 0.2
14. Titanium dioxide 8.0
15. Talc 4.0
16. Bengala 1.0
17. Yellow iron oxide 2.0
18. Appropriate amount of fragrance 19. [Manufacturing method] Ingredients 2 to 8 having a total amount of 100 in purified water are dissolved by heating and kept at 80 ° C. to prepare an oil phase. Ingredient 9 is well swollen with ingredient 19, then ingredients 1 and 10-13 are added and mixed uniformly. Ingredients 14 to 17 pulverized and mixed by a pulverizer are added thereto, and the mixture is stirred with a homomixer and kept at 75 ° C. to prepare an aqueous phase. Add the aqueous phase to the oil phase while stirring to emulsify. Then, it is cooled, the component 18 is added at 45 ° C., and the product is cooled to 30 ° C. while stirring.
（処方例７） 浴用剤
処方 含有量（％）
１．セイヨウナナカマドの果実のエタノ－ル抽出物（製造例３） １．０
２．炭酸水素ナトリウム ５０．０
３．黄色２０２号（１） 適量
４．香料 適量
５．硫酸ナトリウムにて全量を１００とする
［製造方法］成分１～５を均一に混合し製品とする。
(Prescription example 7) Prescription content for bath (%)
1. 1. Ethanol extract of rowan fruit (Production Example 3) 1.0
2. 2. Sodium bicarbonate 50.0
3. 3. Yellow No. 202 (1) Appropriate amount 4. Appropriate amount of fragrance 5. [Manufacturing method] Ingredients 1 to 5 having a total amount of 100 with sodium sulfate are uniformly mixed to prepare a product.
（処方例８） 軟膏
処方 含有量（％）
１．セイヨウナナカマドの果実の熱水抽出物（製造例１） ５．０
２．セイヨウナナカマドの果実の
１，３－ブチレングリコ－ル抽出物（製造例４） １．０
３．ポリオキシエチレンセチルエ－テル（３０Ｅ．Ｏ．） ２．０
４．モノステアリン酸グリセリン １０．０
５．流動パラフィン ５．０
６．セタノ－ル ６．０
７．パラオキシ安息香酸メチル ０．１
８．プロピレングリコ－ル １０．０
９．精製水にて全量を１００とする
［製造方法］成分３～６を加熱溶解して混合し、７０℃に保ち油相とする。成分１、２及び７～９を加熱溶解して混合し、７５℃に保ち水相とする。油相に水相を加えて乳化して、かき混ぜながら３０℃まで冷却して製品とする。
(Prescription example 8) Ointment prescription content (%)
1. 1. Hot water extract of rowan fruit (Production Example 1) 5.0
2. 2. Rowan rowan fruit 1,3-butylene glycol extract (Production Example 4) 1.0
3. 3. Polyoxyethylene cetyl ether (30EO) 2.0
4. Glycerin monostearate 10.0
5. Liquid paraffin 5.0
6. Setanol 6.0
7. Methyl paraoxybenzoate 0.1
8. Propylene Glico 10.0
9. [Manufacturing method] Ingredients 3 to 6 having a total amount of 100 in purified water are melted by heating and mixed, and kept at 70 ° C. to prepare an oil phase. Ingredients 1, 2 and 7 to 9 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 to obtain a product.
（処方例９） 散剤
処方 含有量（％）
１．セイヨウナナカマドの果実の熱水抽出物（製造例１） １．０
２．乾燥コ－ンスタ－チ ３９．０
３．微結晶セルロ－ス ６０．０
［製造方法］成分１～３を混合し、散剤とする。
(Prescription example 9) Powder prescription content (%)
1. 1. Hot water extract of rowan fruit (Production Example 1) 1.0
2. 2. Dry cone structure 39.0
3. 3. Microcrystal Cellulose 60.0
[Manufacturing method] Ingredients 1 to 3 are mixed to prepare a powder.
（処方例１０） 錠剤
処方 含有量（％）
１．セイヨウナナカマドの果実のエタノ－ル抽出物（製造例３） ５．０
２．乾燥コ－ンスタ－チ ２５．０
３．カルボキシメチルセルロ－スカルシウム ２０．０
４．微結晶セルロ－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型する。成型した顆粒に成分６を加えて打錠する。１錠０．５２ｇとする。
(Prescription example 10) Tablet prescription content (%)
1. 1. Ethanol extract of rowan fruit (Production Example 3) 5.0
2. 2. Dry cone start 25.0
3. 3. Carboxymethyl Cellulose Calcium 20.0
4. Microcrystal 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１１） 錠菓
処方 含有量（％）
１．セイヨウナナカマドの果実のエタノ－ル抽出物（製造例３） ２．０
２．乾燥コ－ンスタ－チ ４９．８
３．エリスリト－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 ０．１
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、顆粒成型する。成型した顆粒に成分５及び６を加えて打錠する。１粒１．０ｇとする。
(Prescription example 11) Tablet confectionery prescription content (%)
1. 1. Ethanol extract of rowan fruit (Production Example 3) 2.0
2. 2. Dry cone structure 49.8
3. 3. Ellis Ritol 40.0
4. Citric acid 5.0
5. Sucrose fatty acid ester 3.0
6. Fragrance 0.1
7. Make the total amount 100 with purified water
[Manufacturing method] Ingredients 1 to 4 and 7 are mixed and granulated. Ingredients 5 and 6 are added to the molded granules and the mixture is locked. One grain is 1.0 g.
（処方例１２） 飲料
処方 含有量（％）
１．セイヨウナナカマドの果実の熱水抽出物（製造例１） ０．０５
２．ステビア ０．０５
３．リンゴ酸 ５．０
４．香料 ０．１
５．精製水にて全量を１００とする
［製造方法］成分２及び３を少量の水に溶解する。次いで、成分１、４及び５を加えて混合する。
(Prescription example 12) Beverage prescription content (%)
1. 1. Hot water extract of rowan fruit (Production Example 1) 0.05
2. 2. Stevia 0.05
3. 3. Malic acid 5.0
4. Fragrance 0.1
5. [Manufacturing method] Ingredients 2 and 3 having a total amount of 100 in purified water are dissolved in a small amount of water. Then, the components 1, 4 and 5 are added and mixed.
以上のことから、本発明のセイヨウナナカマドの果実の抽出物は、優れたコラ－ゲン産生促進作用、ヒアルロン酸産生促進作用、ＭＭＰ阻害作用、メラニン生成抑制作用及び抗酸化作用を有し、安定性にも優れていた。よって、本発明のセイヨウナナカマドの果実の抽出物は、皮膚の老化といった美容分野だけでなく、老化による機能低下の抑制、ガンの予防、治療等といった医療分野にも利用でき、食品、化粧品、医薬部外品及び医薬品等への応用が期待される。 From the above, the fruit extract of rowan of the present invention has excellent collagen production promoting action, hyaluronic acid production promoting action, MMP inhibitory action, melanin production inhibitory action and antioxidant action, and is stable. Was also excellent. Therefore, the extract of the fruit of Rowan of the present invention can be used not only in the beauty field such as skin aging but also in the medical field such as suppression of functional deterioration due to aging, prevention and treatment of cancer, and foods, cosmetics and quasi-drugs. It is expected to be applied to external products and pharmaceuticals.
Claims (8)
A food composition for preventing and improving various diseases, joint diseases and physiological floater caused by an increase in MMP, which comprises an extract of rowan fruit.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2020109853A JP2022022526A (en) | 2020-06-25 | 2020-06-25 | External preparation and internal preparation for skin |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2020109853A JP2022022526A (en) | 2020-06-25 | 2020-06-25 | External preparation and internal preparation for skin |
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| Publication Number | Publication Date |
|---|---|
| JP2022022526A true JP2022022526A (en) | 2022-02-07 |
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|---|---|---|---|
| JP2020109853A Pending JP2022022526A (en) | 2020-06-25 | 2020-06-25 | External preparation and internal preparation for skin |
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| Country | Link |
|---|---|
| JP (1) | JP2022022526A (en) |
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2020
- 2020-06-25 JP JP2020109853A patent/JP2022022526A/en active Pending
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