JP2013144651A - Keratin production promoter, food, skin external preparation, and hair restorer - Google Patents
Keratin production promoter, food, skin external preparation, and hair restorer Download PDFInfo
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- Coloring Foods And Improving Nutritive Qualities (AREA)
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Abstract
Description
本発明は皮膚角層ケラチンタンパク質(以下ケラチン)の産生を促進するケラチン産生促進剤、ケラチン減少による皮膚、爪、毛髪の劣化や老化等の現象の防止・緩和に有用な食品、皮膚外用剤及び育毛剤に関する。 The present invention relates to a keratin production promoter that promotes the production of skin horny layer keratin protein (hereinafter referred to as keratin), a food useful for preventing or alleviating phenomena such as skin, nails, hair deterioration and aging caused by keratin reduction, a skin external preparation, and It relates to hair restorer.
ケラチンは、皮膚の表層の組織である角質や爪、毛髪を構成する主要タンパク質であり、これらの組織が常に新生され成長(新陳代謝)するために非常に重要な役割を果たす。 Keratin is a major protein that constitutes the skin's surface layer, the stratum corneum, nails, and hair, and plays a very important role in the continuous generation and growth (metabolism) of these tissues.
ケラチンはストレスやホルモンバランスの異常、加齢による新陳代謝の衰え等により、産生量が減少する。このことによりケラチン成分の不十分な角質や爪、毛髪が作られ、強度の不足した肌や、脆い爪、コシのなく細い毛髪といった表皮組織の弱体化を招く。特に肌の強度不足は紫外線などの外的刺激、感染症等に対する防御力の低下や老化現象を引き起こすことになる。脆い爪や細い毛髪は、特にマニキュアや染毛を行う時に問題となる。 The production of keratin decreases due to stress, abnormal hormone balance, deterioration of metabolism due to aging, and the like. This produces keratin, nails, and hair with insufficient keratin components, leading to weakening of the skin tissue such as skin with insufficient strength, brittle nails, and firm, thin hair. In particular, insufficient skin strength causes external stimulation such as ultraviolet rays, a decrease in defense against infectious diseases, and an aging phenomenon. Brittle nails and fine hair are particularly problematic when performing manicure and hair coloring.
高分子であるケラチンは消化管や皮膚から吸収されにくいので、ケラチン自体を摂食したり皮膚に塗布しても、表皮組織内のケラチン量の増進につながりにくいと言われている。従って、表皮組織に本来備わっている自然のケラチン産生能を活性化し、ケラチンの産生を促進することにより、ケラチン不足による表皮組織の弱体化を防止し、炎症、感染症、老化等の問題を予防するようなケラチン産生促進剤、食品、皮膚外用剤等が求められている。 Since keratin, which is a polymer, is difficult to be absorbed from the digestive tract and the skin, it is said that even if keratin itself is eaten or applied to the skin, it is difficult to increase the amount of keratin in the epidermis tissue. Therefore, by activating the natural keratin production ability inherent in the epidermal tissue and promoting keratin production, it prevents the weakening of the epidermal tissue due to keratin deficiency and prevents problems such as inflammation, infection, and aging Such keratin production promoters, foods, skin external preparations and the like are demanded.
特開平11−158053号公報は、ウコギ科植物の抽出物等を配合した化粧料が、皮膚の保湿、血行促進、皮膚疾患の改善作用をもつことを開示している。また特開2001−181147号公報は、エゾウコギ抽出物等を配合した毛髪用化粧料が、紫外線吸収作用により毛髪の損傷を防止し、毛髪の亀裂や毛羽立ちを防ぐことを開示している。 Japanese Patent Application Laid-Open No. 11-158053 discloses that cosmetics formulated with an extract of Argiaceae plants have effects of moisturizing the skin, promoting blood circulation, and improving skin diseases. Japanese Patent Laid-Open No. 2001-181147 discloses that a hair cosmetic blended with an extract of Ezokogi prevents hair damage and prevents cracking and fluffing by ultraviolet absorption.
本発明においては、ケラチン産生を促進し、ケラチン減少にともなう強度の不足した肌や、脆い爪、コシのなく細い毛髪といった表皮組織の弱体化を予防・改善しうる新規のケラチン産生促進剤と、それを配合した新規の食品、皮膚外用剤、育毛剤を提供することを目的とする。更に表皮細胞の分化に著しい影響を与えず、従って幹細胞の分化能を維持しつつケラチン産生能のみを増大させるケラチン産生促進剤を提供することも目的とする。 In the present invention, a novel keratin production promoter that promotes keratin production and can prevent and improve skin weakness due to keratin reduction and weakening of epidermal tissues such as brittle nails and firm, thin hair, An object is to provide a novel food, an external preparation for skin, and a hair restorer containing the same. It is another object of the present invention to provide a keratin production promoter that does not significantly affect the differentiation of epidermal cells and therefore increases only the keratin production ability while maintaining the differentiation ability of stem cells.
前記目的を達成するために、本発明者らは、安全性に優れた物質の中から、ケラチン産生促進効果を発現させる物質を得るべく鋭意研究を重ねた結果、従来は強壮作用や抗ストレス作用を有する物質として知られていたエゾウコギ抽出物が顕著なケラチンの産生促進効果を有することを見出し、本発明を完成するに至った。 In order to achieve the above-mentioned object, the present inventors have conducted intensive research to obtain a substance that exhibits a keratin production promoting effect from among substances having excellent safety. It has been found that an extract of Ekogigi, which has been known as a substance having the above, has a remarkable keratin production promoting effect, and has completed the present invention.
エゾウコギ(Siberian ginseng、学名Acanthopanex Senticosusu Harms)はウコギ科の落葉低木であり、滋養・強壮作用や抗ストレス作用のある薬用植物として知られている。本発明に用いられるエゾウコギ抽出物は、エゾウコギの茎、根及び葉などから水又は有機溶媒で抽出する。抽出に用いる有機溶媒は極性溶媒であっても非極性溶媒であってもよく、抽出方法にも特に制限はない。 Siberian ginseng (scientific name Acanthopanex Senticosusu Harms) is a deciduous shrub of the family Araceae and is known as a medicinal plant with nourishing, tonic and anti-stress effects. The sorghum extract used in the present invention is extracted from stalks, roots, leaves and the like of sorghum with water or an organic solvent. The organic solvent used for extraction may be a polar solvent or a nonpolar solvent, and the extraction method is not particularly limited.
本発明のケラチン産生促進剤におけるエゾウコギ抽出物の配合量は剤型や用途に応じて調整することができるが、安定性、安全性などの点から希釈して用いることが好ましい。発明者の実験によれば、エゾウコギ抽出物を単独で用いても、表皮細胞のケラチン産生機能を高め、良好なケラチン産生促進作用を発揮する。比較的低濃度のエゾウコギ抽出物でも効果があるため、これを食品、皮膚外用剤、育毛剤等に安全に配合することができる。 The blending amount of the sorghum extract in the keratin production promoter of the present invention can be adjusted according to the dosage form and application, but it is preferably diluted from the viewpoint of stability and safety. According to the inventor's experiment, even when the sorghum extract is used alone, it enhances the keratin production function of epidermal cells and exhibits a good keratin production promoting effect. Even a relatively low concentration of Ezocogi extract is effective, so it can be safely blended into foods, external preparations for skin, hair restorers and the like.
本発明のケラチン産生促進剤を配合する食品には、必須成分であるエゾウコギ抽出物に加えて、必要に応じ、本発明の効果を損なわない範囲内で甘味料、防腐剤、酸化防止剤、香料、生薬や栄養補助剤等を配合できる。また、本発明のケラチン産生促進剤を配合する食品の形態は、粉末、散剤、顆粒剤、錠剤、カプセル剤等、経口摂取可能な様々な形態をとりうるほか、他の飲食品に添加することもできる。 The food containing the keratin production promoter of the present invention contains, in addition to the essential component Ezoukogi extract, if necessary, a sweetener, an antiseptic, an antioxidant, and a fragrance within a range that does not impair the effects of the present invention. Herbal medicines and nutritional supplements can be added. In addition, the form of food containing the keratin production promoter of the present invention can take various forms that can be taken orally, such as powders, powders, granules, tablets, capsules, etc. You can also.
本発明のケラチン産生促進剤を配合する皮膚外用剤には、必須成分であるエゾウコギ抽出物に加えて、必要に応じ、本発明の効果を損なわない範囲内で化粧料、医薬部外品、医薬品等に一般に用いられる各種成分、水性成分、保湿剤、増粘剤、紫外線吸収剤、紫外線散乱剤、防腐剤、酸化防止剤、香料、色剤、薬剤、生薬等を配合できる。また、本発明のケラチン産生促進剤を配合する皮膚外用剤の剤型は任意であり、例えば化粧水等の可溶化系、乳液、クリーム等の乳化系、あるいは軟膏、粉末分散系、水−油二層系、水−油−粉三層系等のような剤型でもかまわない。 The external preparation for skin containing the keratin production promoter of the present invention includes cosmetics, quasi-drugs and pharmaceuticals as long as they do not impair the effects of the present invention, if necessary, in addition to the essential component sorghum extract For example, various components generally used in the field, aqueous components, humectants, thickeners, ultraviolet absorbers, ultraviolet scattering agents, preservatives, antioxidants, fragrances, colorants, drugs, crude drugs and the like can be blended. The dosage form of the external preparation for skin containing the keratin production promoter of the present invention is arbitrary, for example, a solubilizing system such as lotion, an emulsifying system such as an emulsion or cream, an ointment, a powder dispersion system, or a water-oil. A dosage form such as a two-layer system or a water-oil-powder three-layer system may be used.
本発明のケラチン産生促進剤は、毛髪・爪の主成分であるケラチンを増やすから、育毛剤及び染毛用・マニキュア用薬剤に配合することにより、毛髪・爪等の劣化を効果的に防止することができる。これらの薬剤には、本発明の効果を損なわない範囲で、製剤の機能に必要な他の成分を配合することができる。 Since the keratin production promoter of the present invention increases keratin, which is the main component of hair and nails, it is effectively prevented from deteriorating hair, nails and the like by blending with hair restorers and hair coloring and nail polish agents. be able to. These agents can be blended with other components necessary for the function of the preparation within a range not impairing the effects of the present invention.
以下、本発明を試験的な実施例により詳細に説明する。この説明は本発明の実施方法を明らかにするためのものであり、例示した手法、数値等は発明を限定するものではない。 Hereinafter, the present invention will be described in detail with reference to experimental examples. This description is intended to clarify the method of carrying out the present invention, and the illustrated methods, numerical values, and the like do not limit the invention.
エゾウコギ抽出物のサイトケラチン1産生誘導能の検定試験
<試料>
試料は日本粉末株式会社製のエゾウコギ抽出物(原生薬換算比約20:1)を用いた。
<試験方法>
(試験対象)
ヒト表皮由来細胞株HaCaT細胞をサイトケラチン1産生能の細胞評価系として用いた。HaCaT細胞はヒト表皮での基底層の細胞に相当し、培養条件を変えることにより細胞増殖が停止し、有棘層以降の細胞に分化する形質を現す性質がある。サイトケラチン1は表皮の角質を形成する主成分であり、基底層ではほとんど産生されておらず、有棘層以降から産生が見られるケラチンである。したがって一般的には基底層の細胞が分化した指標(分化マーカー)として扱われている。
Test of cytokeratin 1 production-inducing ability of Ezoukogi extract <Sample>
As a sample, Ezokogi extract (ratio of crude drug equivalent of about 20: 1) manufactured by Nippon Powder Co., Ltd. was used.
<Test method>
(Examination subject)
Human epidermis-derived cell line HaCaT cells were used as a cell evaluation system for cytokeratin 1 production ability. HaCaT cells correspond to cells in the basal layer in the human epidermis, and have the property of exhibiting a trait that causes cell growth to stop and differentiate into spinal and subsequent cells by changing the culture conditions. Cytokeratin 1 is a main component that forms the horny layer of the epidermis, is hardly produced in the basal layer, and is produced from the spinous layer onward. Therefore, it is generally treated as an index (differentiation marker) in which cells in the basal layer are differentiated.
(試験方法)
上記HaCaT細胞株を基本培養液(ダルベッコ改変イーグル培地、培養補助因子としてウシ胎児血清を最終濃度10%で添加)を用いて12穴プラスチックプレート中に1穴あたり1.5×104個(培養面積の約10%を占める培養密度)播種し、5%CO2インキュベータ内で37℃で培養した。
(Test method)
Using the above-mentioned HaCaT cell line with a basic culture solution (Dulbecco's modified Eagle's medium, fetal bovine serum added as a culture auxiliary factor at a final concentration of 10%) in a 12-well plastic plate, 1.5 × 10 4 cells per well (of the culture area) Culture density occupying about 10%) was seeded and cultured at 37 ° C. in a 5% CO 2 incubator.
エゾウコギ抽出物(ESE)を基本培養液に1/100容量添加した培養液(以下、ESE培養液と略す)を調製し、播種後1日目にこれらの培養液へ交換後、4日目に1日目と同じESE培養液と基本培養液のみの2系統の培養液に交換して培養を継続し、ESE添加群及びESE除去群の2系統の細胞培養群を構築した。更に3日後に細胞を回収し、細胞内のサイトケラチン1の有無及び産生変化をウエスタン・ブロット法により解析した。対照群としては、30%エタノールを1/100容量(最終濃度0.3%)添加した培養液にて培養を行った細胞を用いた。サイトケラチン1の検出結果を図1及び図2に示す。 A culture solution (hereinafter abbreviated as ESE culture solution) obtained by adding 1/100 volume of Ezocogi extract (ESE) to the basic culture solution is prepared, and after exchange on these culture solutions on the first day after seeding, on the fourth day. The culture was continued by exchanging the two ESE culture solutions and the basic culture solution only for the first day, and two cell culture groups, an ESE addition group and an ESE removal group, were constructed. Further, after 3 days, the cells were collected, and the presence or absence of cytokeratin 1 in the cells and production changes were analyzed by Western blotting. As a control group, cells cultured in a culture medium supplemented with 1/100 volume of 30% ethanol (final concentration 0.3%) were used. The detection results of cytokeratin 1 are shown in FIGS.
(試験結果)
上記試験の結果、ESE添加群において、サイトケラチン1が通常よりもはるかに多く産生されることが判明した。対照群の細胞ではサイトケラチン1はほとんど産生されなかった。また、エゾウコギ処理を中断するとサイトケラチン1の産生量は速やかに対照群と同程度にまで低下した。顕微鏡による観察結果から、細胞形態(細胞分化)は対照群とほぼ同じ未分化状態であった。これらの結果は、サイトケラチン1の産生量の増加が、幹細胞の分化によるものではなく、各表皮細胞でのサイトケラチン1産生能の直接的な増加によるものであることを示す。
(Test results)
As a result of the above test, it was found that cytokeratin 1 was produced much more than usual in the ESE addition group. Cytokeratin 1 was hardly produced in the cells of the control group. In addition, when the Ekougiri treatment was interrupted, the production amount of cytokeratin 1 rapidly decreased to the same level as that of the control group. From the observation result with a microscope, the cell morphology (cell differentiation) was almost the same as the control group. These results indicate that the increase in the production amount of cytokeratin 1 is not due to the differentiation of stem cells, but is due to the direct increase in the ability to produce cytokeratin 1 in each epidermal cell.
上記より、本発明品にはヒト皮膚の表皮細胞の分化に影響を与えることなく、直接的にサイトケラチン1の産生を強力に誘導する作用があることが明らかとなった。 From the above, it has been clarified that the product of the present invention has an effect of directly inducing the production of cytokeratin 1 directly without affecting the differentiation of epidermal cells of human skin.
一方、表皮におけるケラチンの状態や物性は、NMF(Natural Moisturizing Factor:天然保湿因子)などのアミノ酸量の変化によっても影響を受けることが知られており、例えばNMFをアセトン・エーテル/水処理などにより強制的に除去した荒れ肌モデルにおいては、皮膚の柔軟性低下を伴うケラチン凝集が見られる。凝集したケラチンは単純に水を付与するだけでは再分散せず、角質の水分保持能に影響を及ぼす(非特許文献1)。サイトケラチン1は表皮有棘層で発現し、角化やバリア機能の他に肌のキメの細かさに影響を及ぼす。
そこで荒れ肌の被験者に対してエゾウコギ抽出物含有食品及び皮膚外用剤を適用し、そのサイトケラチン1産生促進作用による皮膚角層状態の変化、特に肌の乾燥、ざらつき、ごわつき、キメの状態や肌荒れに対する改善効果の試験を行った。 Therefore, we apply food containing elephant extract and topical skin preparation to subjects with rough skin, and change the skin stratum corneum due to its cytokeratin 1 production promoting action, especially against dryness, roughness, roughness, texture and rough skin. The improvement effect was tested.
食品製造例1(1)ドリンクの製造:エゾウコギ抽出物を0.1%配合した試験品を表1の通り調製し、1ヶ月間の実使用試験を行った。エゾウコギ抽出物は、エゾウコギの根を30%エタノール水溶液で抽出し原生薬換算値14:1(固形分約35%)で、試験品1本10mL当り原生薬換算50mgを含有する。
パネラーとしては皮膚の乾燥、ざらつき、ごわつき、肌荒れ等の症状を顕著に呈する20代後半〜50代の女性14名にて行った。これらの組成物は1日1回1本10mL、2週間〜1ヶ月使用してもらい、使用性試験前および使用試験終了後に皮膚の状況について「改善した」、「やや改善した」、「変化なし」の3段階にて評価した。試験の結果は各評価を得たパネラー数にて表2に示した。 The panelists were 14 females in their late 20s to 50s who had marked symptoms such as dry skin, roughness, roughness, and rough skin. These compositions are used once a day at 10 mL for 2 weeks to 1 month, and the skin condition was “improved”, “slightly improved”, “no change” before and after the use test. ”Was evaluated in three stages. The test results are shown in Table 2 in terms of the number of panelists that obtained each evaluation.
表2に示されるように、試験品は皮膚のざらつきやごわつきに対しては連用2週間目から改善効果を有し、乾燥や肌荒れに対しても連用するに従い効果が高まることが認められた。また、アレルギー反応や好転反応を示したパネラーはいなかった。 As shown in Table 2, it was confirmed that the test product had an improvement effect from the 2nd week of continuous use on the roughness and roughness of the skin, and that the effect increased as it was used continuously for dryness and rough skin. None of the panelists showed any allergic reaction or improvement.
皮膚外用剤製造例(1)美容液の製造:常法により抽出したエゾウコギ抽出物を用いて、表3記載の組成を有する美容液を製造した。
エゾウコギ抽出物の作製方法は、エゾウコギの根茎の細切り1kgに30v/v%エタノール約5Lを加え、ゆるやかに加熱抽出した後、ろ過した。残渣は30v/v%エタノール約5Lで2回ずつ同様に抽出を行い、全抽出液を合わせて50℃で減圧濃縮を行い、濃縮液約500mLを得た。この液に無水エタノールを適量加えエタノール濃度を30v/v%に調製した。これを7〜10日間冷所に放置して熟成させ、この工程で生じるオリや沈殿をろ過して除去すると同時に30v/v%エタノールを追加して製品500mL を得た。 The method for producing the Ezoukogi extract was to add about 5 L of 30 v / v% ethanol to 1 kg of shredded Rhizome rhizome, gently heat extract and then filter. The residue was extracted twice with about 5 L of 30 v / v% ethanol in the same manner, and all the extracts were combined and concentrated under reduced pressure at 50 ° C. to obtain about 500 mL of the concentrated solution. An appropriate amount of absolute ethanol was added to this solution to adjust the ethanol concentration to 30 v / v%. This was left to stand for 7 to 10 days in a cool place and ripened, and the sediment and precipitate produced in this step were removed by filtration, and at the same time, 30 v / v% ethanol was added to obtain 500 mL of product.
パネラーとして20代以上の女性42名にエゾウコギ配合美容液を1日1〜2回適量を3ヶ月間首に塗布してもらい、皮膚の乾燥、キメ、肌荒れに対する改善効果を評価した(実際の試験は塗布無との比較)。各評価を得たパネラー数は図3〜5及び表4に示す通りであった。
次にパネラーとして27歳女性の首片側に長期連用し、定期的に形態観察を行い、図6、図7の結果を得た。キメ指数は肌の外観のキメの均一性を数値化したもので、均一の場合(最大値)を1とし、乱れるほど数値は低下する。キメ変化率は、首で[左+1.3、右-0.23(18ヶ月)]、デコルテは[左+0.93、右-0.36(14ヶ月)]であり、連用特異的にキメの乱れが改善した。 Next, as a panelist, long-term continuous use on the side of the neck of a 27-year-old woman, the form was regularly observed, and the results shown in FIGS. 6 and 7 were obtained. The texture index is a numerical value of the uniformity of the texture of the skin appearance. The uniform value (maximum value) is 1, and the value decreases as it is disturbed. The rate of change in texture was [left +1.3, right -0.23 (18 months)] in the neck, and [cold] was [left +0.93, right -0.36 (14 months)].
また、パネラーとして6名の首角質の水分量を測定し、エゾウコギ抽出物配合美容液の連用者と非連用者、あるいは連用部位と非連用部位とで比較し、表5、6、及び図8、9の結果を得た。
首片側のみ連用した被験者3名(KT、TS、H)全員で、連用部位特異的に角質水分量が有意に上昇した。(表5及び図8)。製剤を使用しなかった被験者(K)の首は、左右どちらも同等の角質水分量であり、有意差は見られなかった(表6及び図9)。 In all three subjects (KT, TS, H) who continued to use only one side of the neck, the stratum corneum water content increased significantly in a continuous site-specific manner. (Table 5 and FIG. 8). The neck of the subject (K) who did not use the preparation had the same amount of keratinous water on both the left and right sides, and no significant difference was observed (Table 6 and FIG. 9).
首全面に連用した被験者では、4名中2名(TH、MY)で経年的に有意な増大が見られた。有意差が見られた2名の連用期間は5〜10ヶ月であった。冬期の間に連用すれば1.4〜1.8倍、更に長期間連用することで1.2〜2.7倍の角質水分量増大が示された(首での連用)。つまり、連用によって肌の水分保持能が高まることで乾燥を予防し、乾燥による肌荒れやキメの乱れを改善する効果を示すと考える。 Among the subjects who used the entire neck, 2 out of 4 subjects (TH, MY) showed a significant increase over time. The period of continuous use for the two patients who showed a significant difference was 5 to 10 months. When used continuously during the winter, the keratin moisture content increased by 1.4 to 1.8 times, and after prolonged use by 1.2 to 2.7 times (continuous use in the neck). That is, it is considered that the continuous water use increases the moisture retention ability of the skin, thereby preventing dryness and improving the rough skin and the texture disorder caused by the dryness.
皮膚外用剤製造例(2)パック剤の製造:表7Aの成分を加熱溶解し、これに加熱、混合したBの成分を撹拌しながら加え、冷却した後香料を適量加え放置して、表7記載の組成を有するパック剤を製造した。
皮膚外用剤製造例(3)クリームの製造:常法により抽出したエゾウコギ抽出物を用いて、表8記載の組成を有するクリームを製造した。
育毛剤の製造:常法により抽出したエゾウコギ抽出物を用いて、表9及び表10記載の組成を有する育毛剤を製造した。
本発明のケラチン産生促進剤は、ヒト表皮細胞におけるケラチン産生能を飛躍的に増加させる効果があり、またエゾウコギ抽出物は食品、皮膚外用剤などとして投与しうることが知られているから、ケラチン減少にともなう強度の欠けた肌や、脆い爪、コシのなく細い毛髪といった表皮組織の弱体化による紫外線などの外的刺激に対する防御力の低下や肌の老化を予防・改善する効果が期待できる。従って、食品・化粧品・毛髪用化粧品等の製造上有用である。 The keratin production promoter of the present invention has the effect of dramatically increasing the keratin production ability in human epidermal cells, and it is known that the sorghum extract can be administered as a food, a skin external preparation, etc. It can be expected to have an effect of preventing or improving the deterioration of the protective ability against external stimuli such as ultraviolet rays due to weakening of the epidermis tissue such as skin lacking strength due to the decrease, brittle nails, firm and thin hair, and skin aging. Therefore, it is useful in the production of foods, cosmetics, hair cosmetics and the like.
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