JP2019031482A - Pigment cell activator, scf production promoter, and vegf production promoter - Google Patents
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Abstract
Description
本発明は、色素細胞を活性化する色素細胞活性化剤、より詳細には、色素細胞増殖促進剤、メラニン産生促進剤、ＭＩＴＦ産生促進剤、メラニン合成酵素産生促進剤、メラニン輸送促進剤、及びＳＣＦ（幹細胞因子、Stem cell factor、KITL、KIT ligand、Steel factor、Mast cell growth factor）産生促進剤、ＶＥＧＦ（血管内皮細胞増殖因子、Vascular endothelial growth factor）産生促進剤に関する。 The present invention relates to a pigment cell activator that activates pigment cells, more specifically, a pigment cell growth promoter, a melanin production promoter, a MITF production promoter, a melanin synthase production promoter, a melanin transport promoter, and The present invention relates to SCF (Stem cell factor, KITL, KIT ligand, Steel factor, Mast cell growth factor) production promoter and VEGF (Vascular endothelial growth factor) production promoter.
ヒトを含む動物において、皮膚や毛髪の色調は、皮膚及び毛髪に存在する色素であるメラニンの量によって決定されている。メラニンは、表皮基底層や毛包に存在する色素細胞が持つメラニン合成酵素群によって生合成される。現在知られている酵素群は、チロシナーゼ（ＴＹＲ）、チロシナーゼ関連タンパク質１（ＴＹＲＰ１、ＤＨＩＣＡ oxidase）、及びドーパクロムトートメラーゼ（ＤＣＴ、ＴＹＲＰ２）である。さらに、これらの酵素群は、転写因子である小眼球症関連転写因子（ＭＩＴＦ）により遺伝子発現が亢進することが知られている。（非特許文献１、非特許文献２、非特許文献３）。 In animals including humans, the color of skin and hair is determined by the amount of melanin, which is a pigment present in the skin and hair. Melanin is biosynthesized by a group of melanin synthases possessed by pigment cells present in the epidermal basal layer and hair follicles. Currently known enzyme groups are tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1, DHICA oxidase), and dopachrome tomerase (DCT, TYRP2). Furthermore, it is known that gene expression of these enzyme groups is enhanced by a microphthalmia-related transcription factor (MITF) which is a transcription factor. (Non-patent document 1, Non-patent document 2, Non-patent document 3).
色素細胞内で生合成されたメラニンは、細胞内に存在する低分子量Ｇタンパク質ＲＡＢ２７Ａを含む複合体により、輸送される事が知られており（非特許文献３）、このようなメラニン輸送機構により、色素細胞から上皮系細胞内に転送されることで、皮膚や毛髪は着色する。 Melanin biosynthesized in pigment cells is known to be transported by a complex containing a low molecular weight G protein RAB27A present in the cells (Non-patent Document 3). By being transferred from pigment cells into epithelial cells, skin and hair are colored.
ヒトは、美しく白い肌を望む一方、近年の若年層においては、褐色の肌を望む場合も多く、皮膚の褐色化には日光浴を行ったり、屋内で紫外線照射を受けたりすることが行われてきた。しかし、過度の紫外線はＤＮＡ損傷を引き起こし、その結果、皮膚癌等が発症することが知られている。また、ジヒドロキシアセトンなどを主成分とするセルフタンニング剤も知られているが、色合いのコントロールの難しさや紫外線防御能低下の可能性がある。そのため、ＤＮＡ損傷を介さず色素細胞にメラニンを作らせることが求められている。また、メラニンは紫外線照射から皮膚を守る役割を担っており、メラニン産生により皮膚のダメージを予防することができる。 While humans want beautiful white skin, young people in recent years often want brown skin, and the skin browning has been done by sunbathing or indoor UV irradiation. It was. However, it is known that excessive ultraviolet rays cause DNA damage, resulting in skin cancer and the like. In addition, self-tanning agents containing dihydroxyacetone as a main component are also known, but there is a possibility of difficulty in controlling the hue and a decrease in UV protection ability. Therefore, there is a demand for pigment cells to make melanin without DNA damage. Melanin plays a role of protecting the skin from ultraviolet irradiation, and skin damage can be prevented by melanin production.
さらに、色素細胞が消失するか、あるいはその機能が低下してメラニン産生が減少する皮膚疾患（白斑）がある。白斑は先天的な場合もあるが後天的に発症することもあり、治療法としては、日光照射、紫外線照射等の光線療法、ステロイドホルモンの内服、外用等が挙げられるが有効なものがなく、安全性についても問題があるのが現状である。
また、加齢に伴う白髪は、毛包に存在する色素細胞の変化によってメラニンが減少する生理的老化現象の一つであるが、その発生機序の多くは未だ解明されておらず、染毛剤による染毛が中心となっているのが現状である。しかし、これらの白髪染めは、発生した白髪を事後的に黒色に染める対処療法的なものであって、白髪の発生を根本的に解決するものではない。
In addition, there are skin diseases (white spots) in which pigment cells disappear or their function decreases and melanin production decreases. Vitiligo may be congenital but may also be acquired, and treatment methods include phototherapy such as sunlight irradiation, ultraviolet irradiation, internal use of steroid hormones, external use, etc., but there are no effective ones, There is also a problem with safety.
In addition, aging-induced gray hair is one of the physiological aging phenomena in which melanin decreases due to changes in pigment cells present in hair follicles, but many of the mechanisms of its development have not yet been elucidated. The current situation is mainly for hair dyeing with agents. However, these white hair dyes are coping therapy that later dyes the generated white hair black, and do not fundamentally solve the occurrence of white hair.
従って、色素細胞に直接作用して色素細胞を活性化させ、細胞自体の増殖を高めたり、メラニン量を増加させる成分を見出したりすることができれば、本来メラニンが持つ生体防御能を促進させて皮膚のダメージを予防すると共に、肌の褐色化や白斑の予防又は治療、白髪の防止又は改善が実現できると考えられる。 Therefore, if it can act directly on the pigment cells to activate the pigment cells, increase the proliferation of the cells themselves, or find a component that increases the amount of melanin, it promotes the biological defense ability inherent to melanin and promotes skin It is considered that the prevention or treatment of skin browning or vitiligo and the prevention or improvement of gray hair can be realized.
また、ＳＣＦは造血細胞、肥満細胞、色素細胞等、種々の細胞の増殖や分化を促す因子として知られており、造血、精子形成及びメラニン形成において重要な役割を果たしている。皮膚においては角化細胞や線維芽細胞が産生し、色素細胞の増殖やメラニン産生を促すことで、健康的な皮膚色の維持・改善に寄与する。また毛包においては、毛包上皮系細胞やその幹細胞、毛乳頭細胞が産生し、色素細胞やその幹細胞の増殖及び生存能力を向上することで、頭髪や睫毛、その他の体毛色を維持・改善し、白髪を予防、改善することが期待される。 SCF is known as a factor that promotes the proliferation and differentiation of various cells such as hematopoietic cells, mast cells, and pigment cells, and plays an important role in hematopoiesis, spermatogenesis and melanogenesis. In the skin, keratinocytes and fibroblasts are produced, which contributes to the maintenance and improvement of healthy skin color by promoting the proliferation of pigment cells and melanin production. In hair follicles, hair follicle epithelial cells, their stem cells, and dermal papilla cells produce and improve the growth and viability of pigment cells and their stem cells to maintain and improve hair color, eyelashes, and other body color. It is expected to prevent and improve gray hair.
ＶＥＧＦは血管内皮細胞の増殖や生存能力を向上させることで、血管新生・形成に関与する因子として知られる。主に血管内皮細胞表面にある血管内皮細胞増殖因子受容体に結合し、細胞分裂や遊走、分化を刺激したり、微小血管の血管透過性を亢進させたりする働きをもつが、その他単球・マクロファージの活性化にも関与する。皮膚においては角化細胞や線維芽細胞が分泌し、皮膚の血行を促進することによってクスミや透明感の改善等、皮膚色の改善に寄与する。また毛包においては、外毛根鞘細胞等の毛包上皮系細胞や毛乳頭細胞が産生し、毛包周囲の血管網を発達させたり、直接的に種々の細胞増殖を促進することにより、健全な毛髪成長に寄与する。 VEGF is known as a factor involved in angiogenesis and formation by improving the proliferation and viability of vascular endothelial cells. Mainly binds to vascular endothelial growth factor receptor on the surface of vascular endothelial cells, stimulates cell division, migration and differentiation, and enhances vascular permeability of microvessels. Also involved in macrophage activation. In the skin, keratinocytes and fibroblasts are secreted, and contribute to the improvement of skin color, such as the improvement of darkness and transparency by promoting the blood circulation of the skin. In hair follicles, hair follicle epithelial cells such as outer root sheath cells and dermal papilla cells produce and develop a vascular network around the hair follicle or directly promote various cell growth, Contributes to healthy hair growth.
従って、これら因子の産生を促進することで、様々な症状の治療、改善につなげることが可能であると考えられる。これまでに様々な色素細胞活性化剤、ＳＣＦ産生促進剤、及びＶＥＧＦ産生促進剤が見出されている。従来、色素細胞を活性化する成分としては、例えば、チロシナーゼ産生促進剤としてスカシユリ等（特許文献１）、ＭＩＴＦ産生促進剤としてフォルスコリン等（特許文献２）が報告されており、ＳＣＦの発現を促進する成分としては、例えば、ステュライラ、コビダラ、サルマリ等が報告されており（特許文献３）、ＶＥＧＦの発現を促進する成分としては、ゲンコウ、ウンシュウミカン等が知られている（特許文献４）。 Therefore, by promoting the production of these factors, it is considered possible to treat and improve various symptoms. Various pigment cell activators, SCF production promoters, and VEGF production promoters have been found so far. Conventionally, as a component that activates pigment cells, for example, scouring lily (Patent Document 1) as a tyrosinase production promoter, and forskolin (Patent Document 2) as a MITF production promoter have been reported. For example, Stellara, Kovidara, Salmari and the like have been reported as the promoting component (Patent Document 3), and Genko, Satsuma mandarin, etc. are known as the components that promote the expression of VEGF (Patent Document 4). .
一方、オウバクは、ムクロジ目ミカン科キハダ属キハダ又はその他同属植物の周皮を除いた樹皮に由来する生薬であり、消炎、健胃、清熱、解毒などの効能があり、下痢、腹痛、黄疸、湿疹、腫れ物などに用いられており、ヒバマタは、ヒバマタ目ヒバマタ科ヒバマタ属に属する褐藻であり、ターンオーバー促進、免疫力向上、健胃等の作用があることは知られている。また、オウバク、ヒバマタには、ｂＦＧＦ（塩基性繊維芽細胞増殖因子）や白髪に関する作用が報告されている（特許文献５、特許文献６）が、色素細胞活性化、ＳＣＦ産生、ＶＥＧＦ産生に関する作用は報告されていない。 On the other hand, Aubaku is a herbal medicine derived from the bark excluding the pericarp of the staghorn mandarinaceae Acer genus or other related plants, and has effects such as anti-inflammatory, healthy stomach, fever, detoxification, diarrhea, abdominal pain, jaundice, It is used for eczema, swellings, etc. Hibamata is a brown algae belonging to the genus Hibamata, and is known to have effects such as turnover promotion, immunity improvement, and healthy stomach. In addition, the action related to bFGF (basic fibroblast growth factor) and gray hair has been reported to Awaku and Hibamata (Patent Documents 5 and 6), but the actions related to pigment cell activation, SCF production, and VEGF production. Has not been reported.
本発明の目的は、色素細胞活性化剤を提供すること、及びＳＣＦ産生剤又はＶＥＧＦ産生剤を提供することである。本発明のさらなる目的は、色素細胞増殖やメラニン輸送を促す素材、あるいはメラニン、ＭＩＴＦやチロシナーゼ（以下、「ＴＹＲ」ともいう）、チロシナーゼ関連タンパク質１（以下「ＴＹＲＰ１」ともいう）、ドーパクロームトートメラーゼ（以下「ＤＣＴ」ともいう）等のメラニン合成酵素、ＲＡＢ２７Ａ、ＳＣＦ及びＶＥＧＦの産生を促す素材を提供することである。 An object of the present invention is to provide a pigment cell activator and to provide an SCF producing agent or a VEGF producing agent. Further objects of the present invention are materials that promote pigment cell proliferation and melanin transport, or melanin, MITF, tyrosinase (hereinafter also referred to as “TYR”), tyrosinase-related protein 1 (hereinafter also referred to as “TYRP1”), dopachrome tomatomerase. It is to provide a material that promotes the production of melanin synthase, RAB27A, SCF and VEGF such as (hereinafter also referred to as “DCT”).
発明者らは鋭意検討した結果、オウバク又はそのエキスが、優れた色素細胞活性化作用、すなわち、色素細胞増殖促進作用、メラニン産生促進作用、ＭＩＴＦ産生促進作用やチロシナーゼ、チロシナーゼ関連タンパク質１、ドーパクロームトートメラーゼ等のメラニン合成酵素産生促進作用、ＲＡＢ２７Ａ産生促進作用等のメラニン輸送促進作用を有することを見出した。また、オウバク又はそのエキスが、毛乳頭細胞におけるＳＣＦ産生促進作用、ＶＥＧＦ産生促進作用を有することを見出し、さらには、オウバク又はそのエキスのＳＣＦ及びＶＥＧＦの産生促進作用は、ヒバマタと組み合わせると顕著に増強されることも見出し、本発明を完成するに至った。 As a result of intensive studies, the present inventors have found that a buckwheat or its extract has an excellent pigment cell activation effect, that is, pigment cell proliferation promoting effect, melanin production promoting effect, MITF production promoting effect, tyrosinase, tyrosinase-related protein 1, dopachrome It has been found that it has a melanin transport promoting action such as a melanin synthase production promoting action such as totomerase and a RAB27A production promoting action. In addition, it has been found that buckwheat or its extract has an SCF production promoting action and a VEGF production promoting action in hair papilla cells. Furthermore, the SCF and VEGF production promoting action of buckwheat or its extract is notable when combined with hibamata. The inventors have also found that it is enhanced, and have completed the present invention.
すなわち、本発明は、
（１）オウバク又はそのエキスを有効成分とする、色素細胞活性化剤、
（２）オウバク又はそのエキスを有効成分とする、色素細胞増殖促進剤、
（３）オウバク又はそのエキスを有効成分とする、色素細胞におけるメラニン産生促進剤、
（４）オウバク又はそのエキスを有効成分とする、ＭＩＴＦ産生促進剤、
（５）オウバク又はそのエキスを有効成分とする、メラニン合成酵素産生促進剤、
（６）メラニン合成酵素がチロシナーゼ、チロシナーゼ関連タンパク質１、及びドーパクロームトートメラーゼからなる群から選ばれる少なくとも一種である、（５）に記載の産生促進剤
（７）オウバク又はそのエキスを有効成分とする、メラニン輸送促進剤、
（８）オウバク又はそのエキスを有効成分とする、ＲＡＢ２７Ａ産生促進剤、
（９）オウバク又はそのエキスを有効成分とする、ＳＣＦ産生促進剤、
（１０）オウバク又はそのエキスを有効成分とする、ＶＥＧＦ産生促進剤、
（１１）さらにヒバマタ又はそのエキスを含む、請求項９又は１０に記載の産生促進剤、
である。
That is, the present invention
(1) A pigment cell activator comprising a buckwheat or an extract thereof as an active ingredient,
(2) A pigment cell growth promoter comprising a buckwheat or an extract thereof as an active ingredient,
(3) A melanin production promoter in pigment cells, comprising active ingredient of buckwheat or extract thereof,
(4) a MITF production promoter comprising a buckwheat or an extract thereof as an active ingredient,
(5) Melanin synthase production promoter, comprising buckwheat or its extract as an active ingredient,
(6) The production promoter according to (5), wherein the melanin synthase is at least one selected from the group consisting of tyrosinase, tyrosinase-related protein 1, and dopachrome tote merase. Melanin transport promoter,
(8) A RAB27A production promoter comprising a buckwheat or an extract thereof as an active ingredient,
(9) An SCF production promoter comprising a buckwheat or an extract thereof as an active ingredient,
(10) A VEGF production promoter comprising a buckwheat or an extract thereof as an active ingredient,
(11) The production promoter according to claim 9 or 10, further comprising hibermata or an extract thereof,
It is.
本発明の色素細胞活性化剤、ＳＣＦ産生促進剤及びＶＥＧＦ産生促進剤はその優れた作用により色素細胞、ＳＣＦ及びＶＥＧＦに関連した種々の症状や疾患に対する効果が期待できる。また、本発明の色素細胞活性化剤、色素細胞増殖促進剤、メラニン産生促進剤、ＭＩＴＦ産生促進剤、メラニン合成酵素産生促進剤、メラニン輸送促進剤、ＲＡＢ２７Ａ産生促進剤、ＳＣＦ産生促進剤及びＶＥＧＦ産生促進剤は、これらの作用を必要とする化粧品、医薬部外品、医薬品又は飲食品の分野に利用可能である。また、素材スクリーニング等を行なうに際し、陽性対照薬としても用いることが可能である。 The pigment cell activator, SCF production promoter and VEGF production promoter of the present invention can be expected to have an effect on various symptoms and diseases related to pigment cells, SCF and VEGF due to their excellent actions. Further, the pigment cell activator, pigment cell proliferation promoter, melanin production promoter, MITF production promoter, melanin synthase production promoter, melanin transport promoter, RAB27A production promoter, SCF production promoter and VEGF of the present invention Production promoters can be used in the fields of cosmetics, quasi drugs, pharmaceuticals, and foods and drinks that require these actions. In addition, it can be used as a positive control drug when performing material screening or the like.
本発明に用いるオウバクはムクロジ目ミカン科キハダ属キハダ（学名Phellodendron amurense）又はその他同属植物の周皮を除いた樹皮に由来する生薬である。また、本発明に用いるヒバマタ（学名Fucus vesiculosus）は、ヒバマタ目ヒバマタ科ヒバマタ属に属する褐藻である。オウバク及びヒバマタは、生薬末、生薬エキスの形で使用される。本発明に用いる生薬末としては、例えば乾燥刻み加工品を更に細かく粉砕した粉末状の乾燥品としてもよい。 The buckwheat used in the present invention is a herbal medicine derived from the bark excluding the pericarp of the genus Phyrodendron amurense or other related plants. In addition, hibermata (scientific name Fucus vesiculosus) used in the present invention is a brown algae belonging to the genus Hibamata belonging to the order Hibamata. Oubak and hibamata are used in the form of herbal powders and herbal extracts. The herbal powder used in the present invention may be, for example, a powdery dry product obtained by further finely pulverizing a dry cut processed product.
本発明に用いるオウバクエキスは、水、低級脂肪族アルコール（メタノール、エタノール、イソプロピルアルコールなど）、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、ジプロピレングリコール、グリセリンなど）、低級脂肪族ケトン（アセトンなど）などの溶媒や前記溶媒の混液により抽出したものを使用することができるが、このうち多価アルコールと水からなる混液で抽出することが最も好ましい。多価アルコールとしては、好ましくは１，３−ブチレングリコール、又はプロピレングリコールが挙げられるが、１，３−ブチレングリコールが最も好ましい。水と１，３−ブチレングリコールからなる溶媒で抽出する場合、溶媒中における１，３−ブチレングリコールの含有量は、３０〜７０体積％が好ましい。 The buckwheat extract used in the present invention is composed of water, lower aliphatic alcohol (such as methanol, ethanol, isopropyl alcohol), polyhydric alcohol (such as 1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin), lower aliphatic ketone. Although it is possible to use a solvent extracted from a solvent such as acetone (such as acetone) or a mixture of the above solvents, it is most preferable to extract with a mixture of a polyhydric alcohol and water. The polyhydric alcohol is preferably 1,3-butylene glycol or propylene glycol, and most preferably 1,3-butylene glycol. When extracting with the solvent which consists of water and 1, 3- butylene glycol, as for content of 1, 3- butylene glycol in a solvent, 30-70 volume% is preferable.
本発明に用いるヒバマタエキスは、水、低級脂肪族アルコール（メタノール、エタノール、イソプロピルアルコールなど）、多価アルコール（プロピレングリコール、１，３−ブチレングリコール、グリセリン、ジプロピレングリコールなど）、低級脂肪族ケトン（アセトンなど）などの溶媒により抽出したものを使用することができるが、エタノールと水の混液、又は多価アルコールと水の混液で抽出することが好ましく、１，３−ブチレングリコールと水の混液が最も好ましい。水と１，３−ブチレングリコールからなる溶媒で抽出する場合、溶媒中における１，３−ブチレングリコールの含有量は、３０〜７０体積％が好ましい。 Hibamata extract used in the present invention is composed of water, lower aliphatic alcohol (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohol (propylene glycol, 1,3-butylene glycol, glycerin, dipropylene glycol, etc.), lower aliphatic ketone. (Acetone, etc.) can be used, but it is preferably extracted with a mixture of ethanol and water, or a mixture of polyhydric alcohol and water, and a mixture of 1,3-butylene glycol and water. Is most preferred. When extracting with the solvent which consists of water and 1, 3- butylene glycol, as for content of 1, 3- butylene glycol in a solvent, 30-70 volume% is preferable.
また、エキスの形態は特に制限されるものではなく、加熱処理、凍結乾燥あるいは減圧乾燥などの処理により、乾燥エキス末、エキス末、軟エキス、流エキスなどにすることができる。オウバクエキスの市販品としては、オウバク抽出液ＢＧ−Ｊ（丸善製薬製）やオウバクリキッドＢ（一丸ファルコス製）、ヒバマタエキスの市販品としては、カイソウ抽出液ＢＧ−Ｊ（丸善製薬製）やファルコレックスヒバマタ（一丸ファルコス製）等が挙げられる。 The form of the extract is not particularly limited, and it can be made into a dry extract powder, an extract powder, a soft extract, a flow extract, etc. by a treatment such as heat treatment, freeze drying or reduced pressure drying. Examples of commercially available products of Aoba extract include Abou extract BG-J (manufactured by Maruzen Pharmaceutical) and Aoba Crid B (manufactured by Ichimaru Falcos). Rex Hibamata (made by Ichimaru Falcos) and the like.
本発明における色素とは、メラニンであり、本発明における色素細胞とは、色素、すなわちメラニンの産生能を有する細胞、例えば、メラノサイトやメラノーマ細胞であり、由来生物種は問わない。また、未熟な色素細胞である色素芽細胞（メラノブラスト）及び色素幹細胞も含む。 The pigment in the present invention is melanin, and the pigment cell in the present invention is a pigment, that is, a cell having the ability to produce melanin, for example, melanocyte or melanoma cell, and the species of origin is not limited. Also included are pigmented cells (melanoblasts) and pigmented stem cells, which are immature pigmented cells.
本発明における色素細胞活性化とは、色素細胞発生及び活性化のマスターレギュレーターとされるＭＩＴＦの産生促進、色素細胞の増殖促進、メラニン産生促進及びそれに関与する酵素であるチロシナーゼ、チロシナーゼ関連タンパク質１、ドーパクロームトートメラーゼの産生促進、並びにメラニン輸送の促進及びそれに関連するタンパクであるＲＡＢ２７Ａの産生促進等の作用を含む包括的な作用である。本発明における色素細胞活性化作用により、色素細胞の不足、色素細胞におけるメラニン産生能の低下、及び、色素細胞におけるメラニン輸送能の低下を予防及び／又は改善することができる。つまり、これらが原因により発生する種々の症状や疾患、例えば、白髪、白斑等を予防及び／又は改善できる。また、色素細胞活性化剤は、健康的な肌色を目的として利用することができる。 In the present invention, the activation of pigment cells refers to the promotion of MITF production, which is a master regulator of pigment cell generation and activation, the promotion of pigment cell proliferation, the promotion of melanin production, and the enzymes involved in tyrosinase, tyrosinase-related protein 1, This is a comprehensive action including actions such as promotion of production of dopachrome tomatomerase, and promotion of melanin transport and production of RAB27A, which is a protein related thereto. The pigment cell activating action in the present invention can prevent and / or improve the shortage of pigment cells, the decrease in melanin production ability in pigment cells, and the decrease in melanin transport ability in pigment cells. That is, it is possible to prevent and / or improve various symptoms and diseases caused by these causes, such as gray hair and vitiligo. The pigment cell activator can be used for the purpose of healthy skin color.
本発明における色素細胞増殖促進剤によると、色素細胞の数を増加させることにより、メラニン産生を促進することができ、また、本発明におけるメラニン産生促進剤は、色素細胞におけるメラニン産生を促進することで、メラニン不足による諸症状や疾患、前記白髪や白斑等の予防及び／又は改善を目的として使用できる。 According to the pigment cell growth promoter in the present invention, melanin production can be promoted by increasing the number of pigment cells, and the melanin production promoter in the present invention promotes melanin production in pigment cells. Thus, it can be used for the purpose of prevention and / or improvement of various symptoms and diseases due to melanin deficiency, the white hair and vitiligo.
本発明におけるＭＩＴＦとは、小眼球症関連転写因子（microphthalmia-associated transcription factor）とも呼ばれ、メラニン合成酵素をコードしているチロシナーゼ遺伝子、チロシナーゼ関連タンパク質１及びドーパクロームトートメラーゼの発現を制御している転写因子であることが報告されており、ＭＩＴＦの産生促進により、メラニン産生が促進することが知られている。 MITF in the present invention is also called microphthalmia-associated transcription factor, and regulates the expression of tyrosinase gene encoding melanin synthase, tyrosinase-related protein 1 and dopachrome tomatolase. It is reported that melanin production is promoted by promoting production of MITF.
本発明におけるメラニン合成酵素には、例えば、チロシナーゼ、チロシナーゼ関連タンパク質１、ドーパクロームトートメラーゼ等が挙げられる。それぞれメラニン合成における特定の反応を触媒するため、メラニン合成酵素の産生促進により、メラニンの産生が促進される。 Examples of the melanin synthase in the present invention include tyrosinase, tyrosinase-related protein 1, dopachrome tomerase and the like. Since each catalyzes a specific reaction in melanin synthesis, production of melanin is promoted by promoting production of melanin synthase.
チロシナーゼは、メラニン合成の律速酵素であり、メラニン合成の出発物質であるチロシンからドーパ、さらにはドーパからドーパキノンへの変換反応を触媒する。また、ドーパクロームトートメラーゼはドーパクロームからＤＨＩＣＡへの変換、チロシナーゼ関連タンパク質１はＤＨＩＣＡからユーメラニン（黒色メラニン）への変換を触媒する酵素である。 Tyrosinase is a rate-limiting enzyme for melanin synthesis and catalyzes a conversion reaction from tyrosine, which is a starting material for melanin synthesis, to dopa and further from dopa to dopaquinone. In addition, dopachrome tomerase is an enzyme that catalyzes the conversion of dopachrome to DHICA, and tyrosinase-related protein 1 is an enzyme that catalyzes the conversion of DHICA to eumelanin (black melanin).
本発明におけるメラニン輸送とは、色素細胞から毛包や皮膚等の上皮系細胞等へのメラニンの受け渡しを意味し、メラニンを受け取った上皮系細胞が増殖・分化することで色のついた毛や皮膚が形成される。このメラニン輸送過程に異常が生じることも白髪や白斑等につながるため、本発明におけるメラニン輸送促進剤により、このような白髪や白斑等の予防や改善が可能である。 The melanin transport in the present invention means the delivery of melanin from pigment cells to epithelial cells such as hair follicles and skin, etc., and the colored hair and Skin is formed. Since abnormalities in the melanin transport process also lead to gray hair, vitiligo and the like, the melanin transport promoter in the present invention can prevent or improve such white hair and vitiligo.
本発明におけるＲＡＢ２７Ａとは、低分子量Ｇタンパクの一種であり、上記のメラニン輸送において重要な役割を担うことが知られている因子である。 RAB27A in the present invention is a kind of low molecular weight G protein, and is a factor known to play an important role in the above melanin transport.
本発明のＳＣＦ産生促進剤によると、優れたＳＣＦ産生促進作用を通じて、例えば、色素細胞の増殖活性化に基づくメラニン生成作用により、白髪や白斑の予防及び／又は改善、あるいは皮膚においては健康的な肌色を目的として利用することができる。また、ＳＣＦは造血の中心をなすサイトカインであり、多能性造血幹細胞、巨核球系前駆細胞、肥満細胞、赤芽球系前駆細胞、顆粒球・マクロファージ系前駆細胞などに作用し、その増殖や分化を促進するため、これら造血に関連する症状や疾患、例えば、好中球減少症、無顆粒球症の予防及び／又は治療に利用可能である。また、これらの用途以外にもＳＣＦ産生促進作用を発揮することに意義のある全ての用途に用いることができる。 According to the SCF production promoter of the present invention, it is possible to prevent and / or improve gray hair and vitiligo, or to promote healthy skin by virtue of an excellent SCF production promoting action, for example, a melanin producing action based on the proliferation activation of pigment cells. It can be used for the purpose of skin color. SCF is a cytokine that plays a central role in hematopoiesis and acts on pluripotent hematopoietic stem cells, megakaryocyte progenitor cells, mast cells, erythroid progenitor cells, granulocyte / macrophage progenitor cells, In order to promote differentiation, it can be used for the prevention and / or treatment of these hematopoietic-related symptoms and diseases such as neutropenia and agranulocytosis. In addition to these uses, it can be used for all purposes that are meaningful for exerting the SCF production promoting action.
本発明のＶＥＧＦ産生促進剤によると、優れたＶＥＧＦ産生作用を通じて、例えば、毛包周辺の血管新生作用により育毛・養毛・発毛剤として利用できる。また、ＶＥＧＦの強力な血管新生作用により、冠動脈疾患・閉塞性末梢動脈硬化症の治療や、血管形成不全、軟骨損傷、創傷等の改善にも用いることができる。また、これらの用途以外にもＶＥＧＦ産生促進作用を発揮することに意義のある全ての用途に用いることができる。 According to the VEGF production promoter of the present invention, it can be used as a hair growth / hair growth / hair growth agent through an excellent VEGF production action, for example, by an angiogenesis action around the hair follicle. In addition, due to the strong angiogenic action of VEGF, it can be used for treatment of coronary artery disease / occlusive peripheral arteriosclerosis, and for improvement of angiogenesis failure, cartilage damage, wound, and the like. In addition to these uses, it can be used for all purposes that are meaningful for exerting a VEGF production promoting action.
本発明の色素細胞活性化剤、色素細胞増殖促進剤、メラニン産生促進剤、ＭＩＴＦ産生促進剤、メラニン合成酵素産生促進剤、チロシナーゼ産生促進剤、チロシナーゼ関連タンパク質１産生促進剤、ドーパクロームトートメラーゼ産生促進剤、メラニン輸送促進剤、ＲＡＢ２７Ａ産生促進剤、ＳＣＦ産生促進剤又はＶＥＧＦ産生促進剤は、化粧品、医薬部外品、医薬品又は飲食品等として提供することができる。なお、好ましくはヒトに対して適用されるものであるが、作用効果が奏される限りヒト以外の動物に対して適用することもできる。 Pigment cell activator, pigment cell proliferation promoter, melanin production promoter, MITF production promoter, melanin synthase production promoter, tyrosinase production promoter, tyrosinase-related protein 1 production promoter, dopachrome tomatomerase production of the present invention The promoter, melanin transport promoter, RAB27A production promoter, SCF production promoter, or VEGF production promoter can be provided as cosmetics, quasi drugs, pharmaceuticals, foods and drinks, and the like. In addition, although preferably applied to humans, it can also be applied to animals other than humans as long as the effects are exhibited.
投与形態としては、特に限定されるものではないが、外用や内服が挙げられ、好ましくは頭皮を含む皮膚に適用する外用である。本発明を外用で適用する場合の剤形としては、例えば、ローション剤、液剤、クリーム剤、軟膏剤、ゲル剤、スプレー剤、シャンプー、コンディショナー、石鹸等が挙げられ、内服で適用する場合の剤形としては、錠剤、粉末剤、散剤、顆粒剤、液剤、カプセル剤、ドライシロップ剤、ゼリー剤、液状食品、半固形食品、固形食品等が挙げられる。 Although it does not specifically limit as a dosage form, External application and internal use are mentioned, Preferably it is the external application applied to the skin containing a scalp. Examples of the dosage form when the present invention is applied externally include, for example, lotions, liquids, creams, ointments, gels, sprays, shampoos, conditioners, soaps, and the like. Examples of the form include tablets, powders, powders, granules, liquids, capsules, dry syrups, jellies, liquid foods, semi-solid foods, solid foods and the like.
これらは、公知の方法で製造することができる。製造に際しては、本発明の効果を損なわない範囲で、化粧品、医薬部外品、医薬品、飲食品又は試薬に含有可能な種々の添加物を配合することができる。 These can be produced by known methods. In the production, various additives that can be contained in cosmetics, quasi-drugs, pharmaceuticals, foods and drinks, or reagents can be blended within a range that does not impair the effects of the present invention.
本発明の色素細胞活性化剤、色素細胞増殖促進剤、メラニン産生促進剤、ＭＩＴＦ産生促進剤、メラニン合成酵素産生促進剤、チロシナーゼ産生促進剤、チロシナーゼ関連タンパク質１産生促進剤、ドーパクロームトートメラーゼ産生促進剤、メラニン輸送促進剤、ＲＡＢ２７Ａ産生促進剤、ＳＣＦ産生促進剤又はＶＥＧＦ産生促進剤は、例えば、関連する症状や疾患の研究のため、あるいは、色素細胞を活性化するための、又はＳＣＦ産生若しくはＶＥＧＦ産生を促進するための試薬として用いることも可能であり、好適には素材スクリーニング等を行なうに際し陽性対照薬として利用可能である。また、本発明は色素細胞を活性化する方法、すなわち、色素細胞増殖、メラニン産生、ＭＩＴＦ産生、メラニン合成酵素産生、チロシナーゼ産生、チロシナーゼ関連タンパク質１産生、ドーパクロームトートメラーゼ産生、メラニン輸送又はＲＡＢ２７Ａ産生を促進する方法、さらにはＳＣＦ産生又はＶＥＧＦ産生を促進する方法を提供する。色素細胞又はＳＣＦ産生若しくはＶＥＧＦ産生を促進させたい細胞にオウバク若しくはそのエキス、又はオウバク若しくはそのエキス及びヒバマタ若しくはそのエキスを添加する工程を含むことを特徴とする。 Pigment cell activator, pigment cell proliferation promoter, melanin production promoter, MITF production promoter, melanin synthase production promoter, tyrosinase production promoter, tyrosinase-related protein 1 production promoter, dopachrome tomatomerase production of the present invention Accelerators, melanin transport promoters, RAB27A production promoters, SCF production promoters or VEGF production promoters are used, for example, for the study of related symptoms or diseases, or for activating pigment cells or SCF production Alternatively, it can be used as a reagent for promoting VEGF production, and can be preferably used as a positive control agent when performing material screening or the like. The present invention also relates to a method for activating pigment cells, ie, pigment cell proliferation, melanin production, MITF production, melanin synthase production, tyrosinase production, tyrosinase-related protein 1 production, dopachrome tomatomerase production, melanin transport or RAB27A production. And a method for promoting SCF production or VEGF production. It includes a step of adding Aoba or its extract, or Aoba or its extract and Hibamata or its extract to pigment cells or cells to promote SCF production or VEGF production.
本発明のオウバク若しくはそのエキス、又はヒバマタ若しくはそのエキスの配合量は、化粧品、医薬部外品、医薬品、飲食品又は試薬で提供する場合、それぞれ組成物全体に対して０．０００００１〜１０質量％、好ましくは０．０００１〜５質量％、より好ましくは０．００１〜１質量％である。 The amount of the present buckwheat or extract thereof, or hibamata or extract thereof is 0.000001 to 10% by mass with respect to the total composition when provided as a cosmetic, quasi-drug, pharmaceutical, food or drink, or reagent. , Preferably it is 0.0001-5 mass%, More preferably, it is 0.001-1 mass%.
本発明の活性化剤又は促進剤（医薬品、医薬部外品、化粧品、飲食品、試薬等）やその説明書は、色素細胞活性化のために用いられる旨の表示、色素細胞増殖促進のために用いられる旨の表示、色素細胞におけるメラニン産生促進のために用いられる旨の表示、ＭＩＴＦ産生促進のために用いられる旨の表示、メラニン合成酵素産生促進のために用いられる旨の表示、メラニン輸送促進のために用いられる旨の表示、ＲＡＢ２７Ａ産生促進のために用いられる旨の表示、ＳＣＦ産生促進のために用いられる旨の表示、又はＶＥＧＦ産生促進のために用いられる旨の表示を付したものであり得る。ここで、「表示を付した」とは、活性化剤又は促進剤を含む製品の本体、容器、包装などに記載すること、あるいは製品情報を開示する説明書、添付文書、パンフレット、その他の印刷物などの書類に記載すること、及び各種チラシ、インターネットを含む宣伝のために用いられる広告に記載することを含む。 The activator or promoter of the present invention (pharmaceuticals, quasi-drugs, cosmetics, foods and drinks, reagents, etc.) and instructions thereof are used for activating pigment cells, for promoting pigment cell proliferation. Used to promote melanin production in pigment cells, used to promote MITF production, used to promote production of melanin, used to promote melanin synthase production, melanin transport An indication that it is used for promotion, an indication that it is used for promoting RAB27A production, an indication that it is used for promoting SCF production, or an indication that it is used for promoting VEGF production It can be. Here, “labeled” means to be described in the main body, container, packaging, etc. of the product containing the activator or accelerator, or instructions, package inserts, pamphlets, and other printed materials that disclose product information To be described in documents such as, and to be described in advertisements used for advertising including various flyers and the Internet.
以下に実施例および試験例を挙げ、本発明をさらに具体的に説明するが、本発明は実施例に限定されない。 EXAMPLES The present invention will be described more specifically with reference to examples and test examples. However, the present invention is not limited to the examples.
（試験例１）ヒト色素細胞に対する細胞増殖促進作用の評価
＜試験方法＞
ヒト色素細胞（倉敷紡績）を96穴プレートに1.5×104 cells/ウェルの密度で播種し、37℃、CO2 5%にセットしたインキュベーター内で培養した。培地には、DermaLife M Comp kit（倉敷紡績）を用いた。播種翌日に、サプリメントStiMel 8 Life Factor を除いた同培地に交換し、被験物質を添加して、CO2 インキュベーターで3 日間培養した。その後 Cell Counting Kit-8 （同仁化学研究所）を添加し、2 時間培養した後、450 nm における吸光度を測定した。被験物質は、１，３−ブチレングリコール50体積％と水50体積％の混液により抽出したオウバクエキスを図１に記載の終濃度で用いた。コントロールは、オウバク添加群からオウバクエキスを除いたもの（溶媒等の他の条件は全てオウバク添加群と同一）とした。
(Test Example 1) Evaluation of cell growth promoting action on human pigment cells <Test method>
Human pigment cells (Kurashikibo) were seeded in a 96-well plate at a density of 1.5 × 10 4 cells / well and cultured in an incubator set at 37 ° C. and 5% CO 2 . As the medium, DermaLife M Comp kit (Kurashikibo) was used. The day after sowing, the medium was replaced with the same medium excluding the supplement StiMel 8 Life Factor, the test substance was added, and the cells were cultured in a CO 2 incubator for 3 days. Then, Cell Counting Kit-8 (Dojindo Laboratories) was added and incubated for 2 hours, and the absorbance at 450 nm was measured. As the test substance, a buckwheat extract extracted with a mixture of 50% by volume of 1,3-butylene glycol and 50% by volume of water was used at the final concentration shown in FIG. The control was obtained by removing the buckwheat extract from the buckwheat addition group (all other conditions such as the solvent were the same as those of the buckwheat addition group).
＜試験結果＞
細胞増殖促進作用の評価結果を図１に示す。各穴において吸光度からブランク穴（培地及びCell Counting Kit-8 のみ）の吸光度を引いた値を求め、さらにオウバクを添加していないコントロール群の値を100としたときの相対値を算出し評価に用いた。コントロール群と比較してオウバク添加群が有意に高い値を示し、オウバクが色素細胞の増殖促進作用を示すことが確認できた。
<Test results>
The evaluation results of the cell growth promoting action are shown in FIG. For each hole, calculate the value obtained by subtracting the absorbance of the blank hole (medium and Cell Counting Kit-8 only) from the absorbance, and calculate the relative value when the value of the control group without added buckwheat is 100. Using. Compared with the control group, the group added with a buckwheat showed a significantly higher value, and it was confirmed that the buckwheat exhibited a pigment cell growth promoting effect.
（試験例２）マウスメラノーマ細胞に対するメラニン産生促進作用の評価
＜試験方法＞
マウスメラノーマ細胞（B16F1 細胞、DSファーマバイオメディカル）を6穴プレートに1×105 cellsウェルの密度で播種し、37℃、CO2 5%にセットしたインキュベーター内で培養した。翌日に、被験物質を添加し、さらに5日間培養した後、細胞を剥離し回収した。細胞ペレットに１mLのPBSを加えて懸濁し、そのうち0.8mLに1 mol/L 水酸化ナトリウム水溶液を加えて，100℃で加熱することにより溶解した。溶解液の405 nm の吸光度を測定し、化学合成メラニン（シグマアルドリッチ）を用いて作成した検量線に当てはめることでメラニン濃度を算出した。残り0.2mLの細胞懸濁液に1％Triton X-100 溶液を添加して溶解し、溶解液のタンパク質濃度をPierce BCA Protein Assay Kit （サーモフィッシャーサイエンティフィック）のプロトコールに従い測定した。細胞各穴のメラニン量とタンパク量から、各穴のタンパク質量あたりのメラニン量（μg melanin /μg protein）を求めた。被験物質は、１，３−ブチレングリコール50体積％と水50体積％の混液により抽出したオウバクエキスを図２に記載の終濃度で用いた。コントロールは、オウバク添加群からオウバクエキスを除いたもの（溶媒等の他の条件は全てオウバク添加群と同一）とした。
(Test Example 2) Evaluation of melanin production promoting action on mouse melanoma cells <Test method>
Mouse melanoma cells (B16F1 cells, DS Pharma Biomedical) were seeded in 6-well plates at a density of 1 × 10 5 cells well and cultured in an incubator set at 37 ° C. and 5% CO 2 . On the next day, the test substance was added, and after further culturing for 5 days, the cells were detached and collected. 1 mL of PBS was suspended in the cell pellet, and 1 mol / L sodium hydroxide aqueous solution was added to 0.8 mL of the cell pellet, followed by heating at 100 ° C. to dissolve. The absorbance at 405 nm of the lysate was measured, and the concentration of melanin was calculated by applying it to a calibration curve prepared using chemically synthesized melanin (Sigma Aldrich). The remaining 0.2 mL of the cell suspension was dissolved by adding 1% Triton X-100 solution, and the protein concentration of the lysate was measured according to the protocol of Pierce BCA Protein Assay Kit (Thermo Fisher Scientific). From the amount of melanin and the amount of protein in each cell hole, the amount of melanin (μg melanin / μg protein) per amount of protein in each hole was determined. As the test substance, a buckwheat extract extracted with a mixture of 50% by volume of 1,3-butylene glycol and 50% by volume of water was used at the final concentration shown in FIG. The control was obtained by removing the buckwheat extract from the buckwheat addition group (all other conditions such as the solvent were the same as those of the buckwheat addition group).
＜試験結果＞
メラニン産生促進作用の評価結果を図２に示す。オウバクを添加していないコントロール群の値を1 としたときの相対値を算出し、評価に用いた。コントロール群と比較してオウバク添加群が有意に高い値を示した。
<Test results>
The evaluation result of the melanin production promoting action is shown in FIG. A relative value was calculated when the value of the control group to which no buckwheat was added was 1, and used for evaluation. Compared with the control group, the Awaku addition group showed a significantly higher value.
（試験例３）ヒト色素細胞に対する遺伝子発現促進作用の評価
＜試験方法＞
ヒト色素細胞（倉敷紡績）を培養プレートに播種し、サブコンフルエントになるまで、37℃、CO2 5%にセットしたインキュベーター内で培養した。培地には、DermaLife M Comp kit（倉敷紡績）を用いた。培養後、StiMel 8 Life Factor を除く同培地に交換し、被験物質を添加して48時間培養した。その後、ライセートバッファーを添加して細胞を溶解し、細胞溶解液を回収した。細胞溶解液より、RNeasy Mini Kit（キアゲン）を用いて添付のプロトコールに従いRNAを回収し、これを鋳型として、Prime Script RT Master mix（タカラバイオ）を用いた逆転写反応によりcDNAを合成した。合成したcDNAから、リアルタイムPCRシステム（Step One Plus、サーモフィッシャーサイエンティフィック）により、GAPDH、MITF、TYR、TYRP1、DCT及びRAB27AのmRNAの発現量をSYBR Green法により測定し、MITF、TYR、TYRP1、DCT及びRAB27Aの発現量をGAPDH発現量により補正した。プライマーは、次の型番のものを用いた。GAPDH：HA067812、MITF：HA153228、TYR：HA286635、TYRP1：HA255361、DCT：HA169364、RAB27A：HA182623（いずれもタカラバイオ）。被験物質は、１，３−ブチレングリコール50体積％と水50体積％の混液により抽出したオウバクエキスを図３〜７に記載の終濃度で用いた。コントロールは、オウバク添加群からオウバクエキスを除いたもの（溶媒等の他の条件は全てオウバク添加群と同一）とした。
(Test Example 3) Evaluation of gene expression promoting action on human pigment cells <Test method>
Human pigment cells (Kurashikibo) were seeded on a culture plate and cultured in an incubator set at 37 ° C. and 5% CO 2 until they became subconfluent. As the medium, DermaLife M Comp kit (Kurashikibo) was used. After culturing, the medium was replaced with the same medium except for StiMel 8 Life Factor, and the test substance was added and cultured for 48 hours. Thereafter, lysate buffer was added to lyse the cells, and the cell lysate was collected. RNA was collected from the cell lysate using RNeasy Mini Kit (Qiagen) according to the attached protocol, and cDNA was synthesized by reverse transcription using Prime Script RT Master mix (Takara Bio) using this as a template. From the synthesized cDNA, the expression level of GAPDH, MITF, TYR, TYRP1, DCT and RAB27A mRNA was measured by the SYBR Green method using a real-time PCR system (Step One Plus, Thermo Fisher Scientific), and MITF, TYR, TYRP1 The expression levels of DCT and RAB27A were corrected by the GAPDH expression level. Primers with the following model numbers were used. GAPDH: HA067812, MITF: HA153228, TYR: HA286635, TYRP1: HA255361, DCT: HA169364, RAB27A: HA182623 (all Takara Bio). As the test substance, an extract of buckwheat extracted with a mixed solution of 50% by volume of 1,3-butylene glycol and 50% by volume of water was used at the final concentration shown in FIGS. The control was obtained by removing the buckwheat extract from the buckwheat addition group (all other conditions such as the solvent were the same as those of the buckwheat addition group).
＜試験結果＞
遺伝子発現促進作用の評価結果を図３〜７に示す。オウバクを添加していないコントロール群の値を1 としたときの相対値を算出し、評価に用いた。オウバク添加群で、MITF、TYR、TYRP1、DCT及びRAB27A 発現量の有意な上昇が確認された。
<Test results>
The evaluation results of the gene expression promoting action are shown in FIGS. A relative value was calculated when the value of the control group to which no buckwheat was added was 1, and used for evaluation. Significant increases in the expression levels of MITF, TYR, TYRP1, DCT, and RAB27A were confirmed in the added group.
（試験例４）ヒト毛乳頭細胞に対するSCF及びVEGF産生促進作用の評価
＜試験方法＞
ヒト毛乳頭細胞（東洋紡）を培養プレートに播種し、サブコンフルエントになるまで、37℃、CO2 5%にセットしたインキュベーター内で培養した。培地には、12%FBS及び規定量のペニシリン・ストレプトマイシンを含むEarle’s MEM（いずれもサーモフィッシャーサイエンティフィック）を用いた。培養後、FBS非含有Earle’s MEMに交換し、被験物質を添加して24時間培養した。その後、ライセートバッファーを添加して細胞を溶解し、細胞溶解液を回収した。細胞溶解液より、RNeasy Mini Kit（キアゲン）を用いて添付のプロトコールに従いRNAを回収し、これを鋳型として、Prime Script RT Master mix（タカラバイオ）を用いた逆転写反応によりcDNAを合成した。合成したcDNAから、リアルタイムPCRシステム（Step One Plus、サーモフィッシャーサイエンティフィック）により、GAPDH、SCF及びVEGFそれぞれのmRNAの発現量を測定し（GAPDH及びSCFはSYBR Green法，VEGFはTaqmanプローブ法）、SCF及びVEGFの発現量をGAPDH発現量により補正した。プライマーは、次の型番のものを用いた。GAPDH：HA067812（タカラバイオ）、SCF：HA122146（タカラバイオ）、VEGF（VEGFA）：Hs00900055_m1（サーモフィッシャーサイエンティフィック）。被験物質は、１，３−ブチレングリコール50体積％と水50体積％の混液により抽出したオウバクエキス及びヒバマタエキスを図８〜１１に記載の終濃度で用いた。コントロールは、オウバク又はヒバマタ添加群から当該エキスを除いたもの（溶媒等の他の条件は全てオウバク又はヒバマタ添加群と同一）とした。
(Test Example 4) Evaluation of SCF and VEGF production promoting action on human hair papilla cells <Test method>
Human hair papilla cells (Toyobo) were seeded on a culture plate and cultured in an incubator set at 37 ° C. and 5% CO 2 until they became subconfluent. As a medium, Earle's MEM (both Thermo Fisher Scientific) containing 12% FBS and a prescribed amount of penicillin / streptomycin was used. After culturing, the culture medium was replaced with FBS-free Earle's MEM, added with a test substance, and cultured for 24 hours. Thereafter, lysate buffer was added to lyse the cells, and the cell lysate was collected. RNA was collected from the cell lysate using RNeasy Mini Kit (Qiagen) according to the attached protocol, and cDNA was synthesized by reverse transcription using Prime Script RT Master mix (Takara Bio) using this as a template. From the synthesized cDNA, mRNA expression levels of GAPDH, SCF and VEGF are measured by real-time PCR system (Step One Plus, Thermo Fisher Scientific) (GAPDH and SCF are SYBR Green method, VEGF is Taqman probe method) , SCF and VEGF expression levels were corrected by GAPDH expression levels. Primers with the following model numbers were used. GAPDH: HA067812 (Takara Bio), SCF: HA122146 (Takara Bio), VEGF (VEGFA): Hs00900055_m1 (Thermo Fisher Scientific). The test substance used was a buckwheat extract and a hibermata extract extracted with a mixed solution of 50% by volume of 1,3-butylene glycol and 50% by volume of water at final concentrations shown in FIGS. The control was a group obtained by removing the extract from the group added with Awaku or Hibamata (all other conditions such as the solvent were the same as those added with Awaku or Hibamata).
＜試験結果＞
図８は、オウバク及びヒバマタのSCF産生促進作用を評価した結果である。被験物質を添加していないコントロール群の発現量を１としたときの各群のSCF相対発現量を示す。オウバクは、SCF発現量を有意に増加させた。一方で、ヒバマタは全く作用を示さず、高濃度においてはむしろSCF発現量を低下させた。図９は、オウバク及びヒバマタを混合添加した際のSCF産生促進作用を評価した結果である。オウバク単独添加群と比較して、オウバク及びヒバマタ混合添加群のSCF発現量は有意に高く、驚くべきことにオウバクのSCF産生促進作用はSCF産生抑制作用を示すヒバマタの同時添加により著しく促進されることが判明した。
<Test results>
FIG. 8 shows the results of evaluating the SCF production promoting action of Aoba and Hibamata. The SCF relative expression level of each group when the expression level of the control group to which no test substance is added is taken as 1 is shown. Awaku significantly increased SCF expression. On the other hand, Hibamata had no effect and decreased the expression level of SCF at higher concentrations. FIG. 9 shows the results of evaluating the SCF production promoting effect when mixed and added with buckwheat and hibermata. The SCF expression level of the group added with Awaku and Hibamata was significantly higher than that of the group added with Awaku alone. It has been found.
図１０は、オウバク及びヒバマタのVEGF産生促進作用を評価した結果である。被験物質を添加していないコントロール群の発現量を１としたときの各群のVEGF相対発現量を示す。オウバクはVEGF発現量を有意に増加させた。またヒバマタはごく微弱なVEGF産生促進作用を示した。図１１は、オウバク及びヒバマタを混合添加した際のVEGF産生促進作用を評価した結果である。オウバク及びヒバマタのVEGF産生促進作用は、これらの混合添加により相乗的に促進されることが判明した。 FIG. 10 shows the results of evaluating the VEGF production promoting effect of Aoba and Hibamata. The VEGF relative expression level of each group when the expression level of the control group to which the test substance is not added is 1 is shown. Awaku significantly increased VEGF expression. Hibamata showed very weak VEGF production promoting effect. FIG. 11 shows the results of evaluating the VEGF production promoting effect when mixed and added with Aoba and Hibamata. It was found that the action of promoting the production of VEGF by Aoba and Hibamata is synergistically promoted by the addition of these.
本発明の色素細胞活性化剤は、色素細胞に対し増殖促進作用、メラニン産生促進作用、ＭＩＴＦ、チロシナーゼ、チロシナーゼ関連タンパク質１、ドーパクロームトートメラーゼ及びＲＡＢ２７Ａ産生促進作用を有するため、これらの作用を必要とする化粧品、医薬部外品、医薬品又は飲食品の分野に利用可能である。また、本発明のＳＣＦ及びＶＥＧＦ産生促進剤もこれらの作用を必要とする化粧品、医薬部外品、医薬品又は飲食品の分野に利用可能である。さらに、本発明の色素細胞活性化剤、ＳＣＦ及びＶＥＧＦ産生促進剤は、素材スクリーニング等を行なうに際し、陽性対照薬として用いることができる。 Since the pigment cell activator of the present invention has a growth promoting action, a melanin production promoting action, MITF, tyrosinase, tyrosinase-related protein 1, dopachrome totemerase and RAB27A production promoting action on pigment cells, these actions are necessary. And can be used in the fields of cosmetics, quasi drugs, pharmaceuticals, and foods and drinks. The SCF and VEGF production promoters of the present invention can also be used in the fields of cosmetics, quasi drugs, pharmaceuticals, and foods and drinks that require these actions. Furthermore, the pigment cell activator, SCF, and VEGF production promoter of the present invention can be used as a positive control agent in conducting material screening and the like.
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| KR20210017558A (en) * | 2019-08-08 | 2021-02-17 | 연세대학교 산학협력단 | Rab27b gene expression inhibitor and Composition for preventing hair loss or promoting hair growth comprising the same |
| JP7473331B2 (en) | 2019-07-10 | 2024-04-23 | 株式会社ミルボン | Evaluation method and manufacturing method |
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| JP2016121134A (en) * | 2014-12-25 | 2016-07-07 | 大正製薬株式会社 | Hair improving agent |
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| JP2016121134A (en) * | 2014-12-25 | 2016-07-07 | 大正製薬株式会社 | Hair improving agent |
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| JP7473331B2 (en) | 2019-07-10 | 2024-04-23 | 株式会社ミルボン | Evaluation method and manufacturing method |
| KR20210017558A (en) * | 2019-08-08 | 2021-02-17 | 연세대학교 산학협력단 | Rab27b gene expression inhibitor and Composition for preventing hair loss or promoting hair growth comprising the same |
| KR102488325B1 (en) | 2019-08-08 | 2023-01-12 | 연세대학교 산학협력단 | Rab27b gene expression inhibitor and Composition for preventing hair loss or promoting hair growth comprising the same |
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