JP2024075143A - Stratum corneum peeling improver - Google Patents
Stratum corneum peeling improver Download PDFInfo
- Publication number
- JP2024075143A JP2024075143A JP2022186358A JP2022186358A JP2024075143A JP 2024075143 A JP2024075143 A JP 2024075143A JP 2022186358 A JP2022186358 A JP 2022186358A JP 2022186358 A JP2022186358 A JP 2022186358A JP 2024075143 A JP2024075143 A JP 2024075143A
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- JP
- Japan
- Prior art keywords
- carbon dioxide
- extract
- stratum corneum
- dioxide gas
- tosendan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
【課題】皮膚の角層剥離機能を改善させ、肌の質感を改善する技術の提供。【解決手段】炭酸ガス及びトウセンダン(Melia toosendan Sieb. et Zucc.)の抽出物を有効成分とする、角層剥離改善剤。【選択図】なし[Problem] To provide a technology for improving the skin's stratum corneum peeling function and improving the texture of the skin. [Solution] A stratum corneum peeling improving agent containing carbon dioxide gas and an extract of Melia toosendan Sieb. et Zucc. as active ingredients. [Selected Figures] None
Description
本発明は、角層剥離を正常化する、角層剥離改善剤に関する。 The present invention relates to a stratum corneum peeling improving agent that normalizes stratum corneum peeling.
皮膚は、外界からの異物や微生物の侵入を防ぐとともに、恒常性を維持する機能を有する。表皮の最外層である角層は主に細胞間脂質、天然保湿因子(NMF)、及びタンパク質等から構成される。 The skin functions to prevent the invasion of foreign substances and microorganisms from the outside world and to maintain homeostasis. The stratum corneum, the outermost layer of the epidermis, is mainly composed of intercellular lipids, natural moisturizing factors (NMFs), proteins, etc.
角層の形成には、角層細胞同士の接着構造(コルネオデスモソーム)が重要である。コルネオデスモソームはデスモグレイン1(desmoglein1:DSG1)、デスモコリン1(desmocollin1:DSC1)をはじめ複数のタンパク質から構成される。コルネオデスモソームはプロテアーゼであるカリクレイン5(kallikrein5:KLK5)等により切断される(非特許文献1)。健常な皮膚では、コルネオデスモソームがプロテアーゼによって分解されることで、正常な角層剥離がおこる(非特許文献2)。一方、乾燥肌では、プロテアーゼの活性が低下しており、コルネオデスモソームの分解が抑制されることで角層細胞が堆積するといわれている(非特許文献3)。また、老人性乾皮症においても、角層細胞の堆積が認められる。この他、角層剥離機能の異常をともなう皮膚疾患は多数報告されており、例えばフケ症、尋常性魚鱗癬、伴性遺伝性魚鱗癬、乾癬等が挙げられる(非特許文献4~6)。 The adhesive structure between keratinocytes (corneodesmosomes) is important for the formation of the stratum corneum. Corneodesmosomes are composed of multiple proteins, including desmoglein 1 (DSG1) and desmocollin 1 (DSC1). Corneodesmosomes are cleaved by proteases such as kallikrein 5 (KLK5) (Non-Patent Document 1). In healthy skin, normal stratum corneum peeling occurs when corneodesmosomes are degraded by proteases (Non-Patent Document 2). On the other hand, in dry skin, protease activity is reduced, and it is said that the degradation of corneodesmosomes is inhibited, resulting in the accumulation of keratinocytes (Non-Patent Document 3). Accumulation of keratinocytes is also observed in senile xerosis. In addition, many skin diseases accompanied by abnormalities in the stratum corneum desquamation function have been reported, such as dandruff, ichthyosis vulgaris, X-linked ichthyosis, and psoriasis (Non-Patent Documents 4-6).
上記のような乾燥肌や乾皮症、種々の皮膚疾患では、皮膚表面状態に異常が認められ、肌の質感が損なわれる。これらにともなう外見上の悩みは、感情面のQOLを著しく低下させることから、肌の質感を改善する技術は、美容的な側面のみでなく、人々が健康な生活を保つ上で重要である。 In dry skin, xerosis, and various skin diseases such as those mentioned above, abnormalities are observed in the skin surface condition, and the skin's texture is impaired. The associated concerns about appearance significantly reduce the emotional quality of life, so technology to improve skin texture is important not only from a cosmetic perspective, but also for people to maintain a healthy lifestyle.
これまでに、斯かる改善技術として、炭酸ガスが角層剥離酵素を活性化し、コルネオデスモソームの分解を促進する作用を有することに基づき、炭酸ガスを皮膚の角層剥離機能の改善や皮膚表面形状の早期改善の有効成分として用いることが報告されている(特許文献1)。 As one such improvement technique, carbon dioxide gas has been reported to be used as an active ingredient for improving the skin's stratum corneum exfoliation function and for early improvement of the skin surface shape, based on the fact that carbon dioxide gas has the effect of activating stratum corneum exfoliating enzymes and promoting the decomposition of corneodesmosomes (Patent Document 1).
一方、センレンシ(川楝子)は、センダン科センダン属のトウセンダンの果実を乾燥した生薬であり、薬効として鎮静作用、鎮痛作用、駆虫作用が知られている。また、トウセンダンの抽出物は、美白作用、保湿作用を有することが報告されている(特許文献2及び3)。しかしながら、トウセンダンの抽出物の皮膚の角層剥離機能に対する作用やトウセンダンの抽出物が炭酸ガスの角層剥離改善作用に及ぼす影響については全く知られていない。 On the other hand, Senrenshi (river elm) is a herbal medicine made from the dried fruit of the Tousen tree, which belongs to the Meliaceae family and is known to have sedative, analgesic and anthelmintic effects. Extracts of Tousen tree have also been reported to have whitening and moisturizing effects (Patent Documents 2 and 3). However, nothing is known about the effect of Tousen tree extracts on the skin's exfoliation function or the effect of Tousen tree extracts on the effect of carbon dioxide gas in improving exfoliation of the stratum corneum.
本発明は、皮膚の角層剥離機能を改善させ、肌の質感を改善する技術を提供することに関する。 The present invention relates to providing a technology that improves the skin's stratum corneum desquamation function and improves skin texture.
本発明者らは、上記課題に鑑み鋭意検討した結果、トウセンダンの抽出物が、単独ではコルネオデスモソームの分解を促進する作用を示さないものの、炭酸ガスと併用することで、炭酸ガスのコルネオデスモソームの分解を促進する作用を増強できることを見出した。 As a result of intensive research conducted in light of the above problems, the present inventors have found that although an extract of Tosendan alone does not exhibit the effect of promoting the decomposition of corneodesmosomes, when used in combination with carbon dioxide, the effect of carbon dioxide in promoting the decomposition of corneodesmosomes can be enhanced.
すなわち、本発明は、以下の1)~5)に係るものである。
1)炭酸ガス及びトウセンダンの抽出物を有効成分とする、角層剥離改善剤。
2)炭酸ガス及びトウセンダンの抽出物を有効成分とする、角層細胞間接着タンパク質分解促進剤。
3)炭酸ガス及びトウセンダンの抽出物を有効成分とする、肌の質感改善剤。
4)トウセンダンの抽出物を有効成分とする、炭酸ガスの角層剥離改善作用の増強剤。
5)トウセンダンの抽出物を有効成分とする、炭酸ガスの角層細胞間接着タンパク質分解促進作用の増強剤。
That is, the present invention relates to the following 1) to 5).
1) A stratum corneum peeling improving agent containing carbon dioxide gas and an extract of Tosendan (Citrus officinalis) as active ingredients.
2) A stratum corneum intercellular adhesion protein decomposition promoter, the active ingredients of which are carbon dioxide gas and an extract of Tosendan.
3) A skin texture improving agent containing carbon dioxide gas and extract of Tosendan as active ingredients.
4) An enhancer for improving the peeling action of carbon dioxide gas, containing an extract of Tosendan as the active ingredient.
5) An enhancer for promoting the decomposition of intercellular adhesion proteins in the stratum corneum by carbon dioxide, the active ingredient being an extract of Tosendan.
本発明によれば、炭酸ガス及びトウセンダンの抽出物の皮膚への適用により、炭酸ガスの角層細胞間接着タンパク質分解促進作用を増強し、角層剥離を効果的に正常化することができ、健全な角層形成を促し、肌の質感を改善することが可能となる。 According to the present invention, the application of carbon dioxide gas and an extract of Tosendan to the skin enhances the effect of carbon dioxide gas in promoting the decomposition of intercellular adhesion proteins in the stratum corneum, effectively normalizing stratum corneum desquamation, promoting healthy stratum corneum formation, and improving skin texture.
本明細書中で引用された全ての特許文献、非特許文献、及びその他の刊行物は、その全体が本明細書中において参考として援用される。 All patents, non-patent literature, and other publications cited herein are hereby incorporated by reference in their entirety.
後記実施例に示すとおり、炭酸ガスとトウセンダンの抽出物をヒト3次元培養表皮に適用した場合、それぞれ単独での適用の場合と比べて、角層中のデスモグレイン1(DSG1)の分解亢進が認められる。炭酸ガスが角層中のDSG1の分解促進作用を有することが知られている(前記特許文献1)一方、トウセンダンの抽出物単独ではDSG1分解促進作用が認められないことから、斯かる効果は、トウセンダンの抽出物が炭酸ガスのDSG1分解促進作用を増強することにより得られるものであることが明らかである。また、炭酸ガスとトウセンダンの抽出物を含有する組成物をヒトの肌に適用した場合、肌のなめらかさ、しっとり感、柔らかさに代表される肌の質感の改善が認められる。
前述したとおり、健常な皮膚では、角層細胞同士の接着構造(コルネオデスモソーム)を構成するDSG1等の角層細胞間接着タンパク質が角層剥離酵素により切断され分解されることにより、正常な角層剥離が起こると考えられている(非特許文献2)。
これらのことから、炭酸ガスとトウセンダンの抽出物の組み合わせは、角層細胞間接着タンパク質分解促進作用、角層剥離改善作用、肌の質感改善作用を有する。また、トウセンダンの抽出物は、炭酸ガスの角層細胞間接着タンパク質分解促進作用の増強作用、角層剥離改善作用の増強作用を有する。
As shown in the examples below, when carbon dioxide gas and an extract of Tosendan are applied to human three-dimensional cultured epidermis, decomposition of desmoglein 1 (DSG1) in the stratum corneum is enhanced compared to the case of application of each alone. Carbon dioxide gas is known to have an action of promoting decomposition of DSG1 in the stratum corneum (Patent Document 1), while an extract of Tosendan alone does not have an action of promoting DSG1 decomposition, so it is clear that such an effect is obtained by the extract of Tosendan enhancing the action of carbon dioxide gas to promote DSG1 decomposition. In addition, when a composition containing carbon dioxide gas and an extract of Tosendan is applied to human skin, improvement in the texture of the skin, represented by skin smoothness, moist feeling, and softness, is observed.
As mentioned above, in healthy skin, it is believed that normal stratum corneum desquamation occurs when intercellular adhesion proteins such as DSG1, which constitute the adhesion structures (corneodesmosomes) between stratum corneum cells, are cleaved and degraded by stratum corneum desquamating enzymes (Non-Patent Document 2).
From these findings, the combination of carbon dioxide gas and extract of Tosendan has the effect of promoting the decomposition of stratum corneum intercellular adhesion proteins, improving stratum corneum desquamation, and improving skin texture. In addition, extract of Tosendan has the effect of enhancing the effect of carbon dioxide gas in promoting the decomposition of stratum corneum intercellular adhesion proteins and enhancing the effect of improving stratum corneum desquamation.
したがって、炭酸ガスとトウセンダンの抽出物の組み合わせは、角層細胞間接着タンパク質分解促進剤、角層剥離改善剤、肌の質感改善剤(以下、「角層剥離改善剤等」とも称する)となり得、またこれらを製造するために使用することができる。炭酸ガスとトウセンダンの抽出物の組み合わせをヒトの皮膚に供給することにより、角層細胞間接着タンパク質の分解を促進し、角層剥離を改善し、また肌の質感を改善することができる。炭酸ガスとトウセンダンの抽出物の組み合わせは、角層細胞間接着タンパク質分解促進のため、角層剥離改善のため、肌の質感改善のために使用することができる。
また、トウセンダンの抽出物は、炭酸ガスの角層細胞間接着タンパク質分解促進作用の増強剤、炭酸ガスの角層剥離改善作用の増強剤(以下、「炭酸ガスの角層剥離改善作用の増強剤等」とも称する)となり得、またこれらを製造するために使用することができる。トウセンダンの抽出物をヒトの皮膚に供給することにより、炭酸ガスの角層細胞間接着タンパク質の分解促進作用を増強し、炭酸ガスの角層剥離改善作用を増強することができる。トウセンダンの抽出物は、炭酸ガスの角層細胞間接着タンパク質分解促進作用の増強のため、炭酸ガスの角層剥離改善作用の増強のために使用することができる。
Therefore, the combination of carbon dioxide gas and the extract of Tosendan can be an agent for promoting the decomposition of stratum corneum intercellular adhesion proteins, an agent for improving stratum corneum delamination, and an agent for improving skin texture (hereinafter also referred to as "agent for improving stratum corneum delamination, etc."), and can be used to produce these. By supplying the combination of carbon dioxide gas and the extract of Tosendan to human skin, it is possible to promote the decomposition of stratum corneum intercellular adhesion proteins, improve stratum corneum delamination, and improve skin texture. The combination of carbon dioxide gas and the extract of Tosendan can be used to promote the decomposition of stratum corneum intercellular adhesion proteins, improve stratum corneum delamination, and improve skin texture.
In addition, the extract of Tosendan can be an enhancer of the action of carbon dioxide gas promoting the decomposition of intercellular adhesion proteins in stratum corneum, and an enhancer of the action of carbon dioxide gas improving stratum corneum delamination (hereinafter also referred to as "enhancer of the action of carbon dioxide gas improving stratum corneum delamination, etc."), and can be used to produce these. By supplying the extract of Tosendan to human skin, the action of carbon dioxide gas promoting the decomposition of intercellular adhesion proteins in stratum corneum can be enhanced, and the action of carbon dioxide gas improving stratum corneum delamination can be enhanced. The extract of Tosendan can be used to enhance the action of carbon dioxide gas promoting the decomposition of intercellular adhesion proteins in stratum corneum, and to enhance the action of carbon dioxide gas improving stratum corneum delamination.
ここで、炭酸ガスとトウセンダンの抽出物の組み合わせ又はトウセンダンの抽出物のヒトへの使用は、治療的使用であってもよいが、非治療的使用であってもよい。「非治療的」とは、医療行為を含まない、すなわち人間を手術、治療又は診断する方法を含まない、より具体的には医師、又は医療従事者もしくは医師の指示を受けた者が人間に対して手術、治療又は診断を実施する方法を含まない概念である。本発明において、非治療的使用としては、美容的又は審美的な目的での角層剥離改善のための炭酸ガスとトウセンダンの抽出物の組み合わせ又はトウセンダンの抽出物の使用、例えばエステティシャン、美容師、理容師、トリマー等による使用等が挙げられる。 Here, the combination of carbon dioxide gas and an extract of Tosendan or the use of the extract of Tosendan on humans may be therapeutic use, but may also be non-therapeutic use. "Non-therapeutic" is a concept that does not include medical procedures, i.e., does not include methods of surgery, treatment, or diagnosis on humans, and more specifically does not include methods of surgery, treatment, or diagnosis on humans by doctors, medical professionals, or persons under the instructions of doctors. In the present invention, non-therapeutic use includes the combination of carbon dioxide gas and an extract of Tosendan or the use of an extract of Tosendan for improving stratum corneum peeling for cosmetic or aesthetic purposes, for example, use by estheticians, hairdressers, barbers, trimmers, etc.
本発明において、「角層細胞間接着タンパク質」とは、角層細胞同士の接着構造(コルネオデスモソーム)を構成するタンパク質を意味し、例えばデスモグレイン1(DSG1)、デスモコリン1(DSC1)、コルネオデスモシン(CDSN)等が挙げられ、好ましくはDSG1である。
本発明において、「角層剥離」とは、角層細胞間の接着機構が弱まって、古い角層細胞が皮膚表面からはがれ落ちることを意味し、その改善とは角層剥離の遅延を抑制し、又は角層剥離を促進し、正常化することを指す。
本発明において、「肌の質感の改善」とは、触知により評価される肌の状態の悪化の抑制又は向上を指し、具体的には角層剥離の改善による健全な角層形成を介した肌の質感の改善である。肌の質感としては、なめらかさ、しっとり感、柔らかさ等が挙げられ、好ましくはなめらかさである。ここで、肌のなめらかさとは肌表面を指で触った際の滑る感触、つるつるする感触のことをいい、しっとり感とは適度な水分を含み肌が潤っていることをいい、柔らかさとは肌が柔軟であることをいう。肌の質感は、官能評価、例えば専門判定員が各種評価基準によりスコア化することにより評価することができる。または機器測定において、例えば、なめらかさであれば皮膚表面における摩擦係数、しっとり感であれば角層水分量、柔らかさであれば皮膚の硬度や弾性係数などを指標として評価することも可能である。皮膚の質感の改善は、スコアの大小、機器測定における各種指標の測定値の大小に基づいて判定することができる。または肌の質感の改善度合いについての定性的な評価、例えばホームユーステストにおけるアンケート結果を集計することによって判定することも可能である。
In the present invention, the term "intercellular adhesion protein" refers to a protein that constitutes the adhesive structure (corneodesmosome) between stratum corneum cells, and examples thereof include desmoglein 1 (DSG1), desmocollin 1 (DSC1), corneodesmosin (CDSN), etc., with DSG1 being preferred.
In the present invention, "stratum corneum desquamation" means that the adhesive mechanism between stratum corneum cells weakens, causing old stratum corneum cells to peel off from the skin surface, and improvement therein means suppressing the delay in stratum corneum desquamation or promoting or normalizing stratum corneum desquamation.
In the present invention, "improvement of skin texture" refers to suppression or improvement of deterioration of skin condition evaluated by touch, specifically, improvement of skin texture through healthy stratum corneum formation by improvement of stratum corneum peeling. Examples of skin texture include smoothness, moistness, softness, etc., and preferably smoothness. Here, smoothness of skin refers to a slippery feeling or a smooth feeling when touching the skin surface with a finger, moistness refers to skin that contains moderate moisture and is moisturized, and softness refers to skin that is soft. Skin texture can be evaluated by sensory evaluation, for example, by a professional judge scoring according to various evaluation criteria. Alternatively, in instrumental measurement, for example, smoothness can be evaluated using the coefficient of friction on the skin surface, moistness can be evaluated using the moisture content of the stratum corneum, and softness can be evaluated using the hardness or elasticity coefficient of the skin as an index. Improvement of skin texture can be judged based on the magnitude of the score and the magnitude of the measured values of various indexes in instrumental measurement. Alternatively, the degree of improvement in skin texture can be qualitatively evaluated, for example, by compiling the results of a questionnaire in a home use test.
本発明において、トウセンダンとは、センダン科センダン属のトウセンダン(Melia toosendan Sieb. et Zucc.)を指す。トウセンダンの果実を乾燥したものは、川楝子(センレンシ)と呼ばれる生薬として知られている。 In the present invention, tousendan refers to tousendan (Melia toosendan Sieb. et Zucc.) of the Meliaceae family, Meliaceae genus. Dried fruits of tousendan are known as a herbal medicine called Senrenshi.
本発明において用いるトウセンダンは、全ての任意の部分が使用可能である。例えば、全木又は任意の部位(根、根茎、幹、枝、茎、葉、樹皮、樹液、樹脂、花、果実、種子、果皮、莢、芽、花穂、心材等)、及びそれらの組み合わせのいずれか1つ又は複数を用いることができる。このうち、果実を用いるのが好ましい。また、トウセンダンの果実を用いる場合、生薬のセンレンシを用いてもよい。 Any part of the Tosendan plant can be used in the present invention. For example, the whole tree or any part (roots, rhizomes, trunks, branches, stems, leaves, bark, sap, resin, flowers, fruits, seeds, pericarp, pods, buds, inflorescences, heartwood, etc.), or any combination thereof, can be used. Of these, it is preferable to use the fruits. When using the fruits of Tosendan, the herbal medicine Senrenshi can also be used.
トウセンダンの抽出物の製造方法については特に限定はなく、トウセンダンを通常の方法で抽出することにより抽出物を得ることができる。具体的には、トウセンダンを乾燥させた乾燥物、その粉砕物等を圧搾抽出することにより得られる搾汁、水蒸気蒸留物、各種抽出溶剤による粗抽出物、粗抽出物を分配又はカラムクロマトなどの各種クロマトグラフィーなどで精製して得られた抽出物画分などを本発明におけるトウセンダンの抽出物として用いることができる。
トウセンダンは生のままで抽出に供することも可能であるが、より抽出効率を高めるために、乾燥、細断、粉砕などの工程を加えることも好ましい。また、本発明においては、上記の抽出物、水蒸気蒸留物、圧搾物等を、いずれかを単独で、又は2種以上を組み合わせて使用してもよい。なかでも、本発明のトウセンダンの抽出物としては、トウセンダンを乾燥させた乾燥物又はその粉砕物から、抽出溶剤を用いて得られた抽出物を用いることがより好ましく、センレンシから抽出溶剤を用いて得られた抽出物を用いることがさらに好ましい。
There is no particular limitation on the method for producing the extract of Tosendan, and the extract can be obtained by extracting Tosendan by a normal method. Specifically, the extract of Tosendan in the present invention can be obtained from a dried product of Tosendan, a squeezed juice obtained by squeezing and extracting a pulverized product thereof, a steam distillate, a crude extract obtained by various extraction solvents, or an extract fraction obtained by purifying a crude extract by partitioning or various chromatographies such as column chromatography.
Although it is possible to subject the tosendan to extraction in its raw form, it is also preferable to add a step such as drying, shredding, or crushing in order to improve the extraction efficiency. In addition, in the present invention, the above-mentioned extract, steam distillate, squeezed product, etc. may be used alone or in combination of two or more. Among them, as the tosendan extract of the present invention, it is more preferable to use an extract obtained from a dried product obtained by drying the tosendan or its crushed product using an extraction solvent, and it is even more preferable to use an extract obtained from Senrenshi using an extraction solvent.
抽出溶剤としては、極性溶剤、非極性溶剤のいずれをも使用することができ、これらを混合して用いることもできる。例えば、水;メタノール、エタノール、プロパノール、ブタノール等の1価アルコール類;エチレングリコール、プロピレングリコール、1,3-ブチレングリコール、ポリエチレングリコール等の多価アルコール類;アセトン、メチルエチルケトン等のケトン類;酢酸メチル、酢酸エチル等のエステル類;テトラヒドロフラン、ジエチルエーテル等の鎖状及び環状エーテル類;ポリエチレングリコール等のポリエーテル類;ジクロロメタン、クロロホルム、四塩化炭素等のハロゲン化炭化水素類;ヘキサン、シクロヘキサン、石油エーテル等の炭化水素類;ベンゼン、トルエン等の芳香族炭化水素類;ピリジン類;超臨界二酸化炭素;油脂、ワックス、その他オイル等が挙げられる。あるいは、上記溶剤の2種以上を組み合わせた混合物を、抽出溶剤として用いることができる。このうち、水、1価又は多価アルコール類、水-1価又は多価アルコール混合液を用いるのが好ましく、1価又は多価アルコール類、水-1価又は多価アルコール混合液を用いるのがより好ましく、1価又多価アルコール類を用いるのがさらに好ましい。ここで1価又は多価アルコール類としては、エタノール、プロピレングリコール、1,3-ブチレングリコールを用いるのが好ましく、エタノール、1,3-ブチレングリコールを用いるのがより好ましく、エタノールを用いるのがさらに好ましい。 As the extraction solvent, either polar or non-polar solvents can be used, and these can also be used in combination. For example, water; monohydric alcohols such as methanol, ethanol, propanol, and butanol; polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and polyethylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate; linear and cyclic ethers such as tetrahydrofuran and diethyl ether; polyethers such as polyethylene glycol; halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; hydrocarbons such as hexane, cyclohexane, and petroleum ether; aromatic hydrocarbons such as benzene and toluene; pyridines; supercritical carbon dioxide; oils and fats, waxes, and other oils. Alternatively, a mixture of two or more of the above solvents can be used as the extraction solvent. Of these, it is preferable to use water, monohydric or polyhydric alcohols, and water-monohydric or polyhydric alcohol mixtures, and it is more preferable to use monohydric or polyhydric alcohols and water-monohydric or polyhydric alcohol mixtures, and it is even more preferable to use monohydric or polyhydric alcohols. Here, as the monohydric or polyhydric alcohols, it is preferable to use ethanol, propylene glycol, or 1,3-butylene glycol, more preferably ethanol or 1,3-butylene glycol, and even more preferably ethanol.
本発明で用いられるトウセンダンの抽出物を得るための抽出条件については、使用する溶剤によって異なり特に制限はないが、例えば水、1価又多価アルコール類又は水-1価又多価アルコール混合液により抽出する場合、好ましくはトウセンダン1質量部に対して1~50容量部の溶剤を用い、好ましくは3~100℃、より好ましくは20~80℃の温度で、好ましくは1時間~数週間、より好ましくは1日~30日間浸漬又は加熱還流するのが好ましい。また、抽出効率を上げる為、併せて攪拌を行ったり、溶媒中でホモジナイズ処理を行ったりしてもよい。 The extraction conditions for obtaining the tosendan extract used in the present invention vary depending on the solvent used and are not particularly limited. For example, when extracting with water, monohydric or polyhydric alcohols, or a water-monohydric or polyhydric alcohol mixture, it is preferable to use 1 to 50 parts by volume of solvent per 1 part by mass of tosendan, and to soak or heat under reflux at a temperature of preferably 3 to 100°C, more preferably 20 to 80°C, for preferably 1 hour to several weeks, more preferably 1 day to 30 days. In addition, stirring or homogenization in the solvent may be performed in order to increase the extraction efficiency.
上記溶媒で抽出して得られたトウセンダンの抽出物はそのまま使用してもよいが、さらに適当な分離手段、例えばゲル濾過、クロマトグラフィー、精密蒸留等により活性の高い画分を分画して用いることもできる。本発明において、トウセンダンの抽出物とは、このようにして得られた各種抽出物、その希釈液、その濃縮液、その精製物又はそれらの乾燥末を包含するものである。 The extract of Tosendan obtained by extraction with the above-mentioned solvent may be used as it is, but it can also be fractionated and used by further separating highly active fractions using suitable separation means such as gel filtration, chromatography, precision distillation, etc. In the present invention, the extract of Tosendan includes the various extracts obtained in this way, their dilutions, their concentrates, their purified products, or their dried powders.
本発明の角層剥離改善剤等は、炭酸ガスとトウセンダンの抽出物を皮膚角層に供給できるものであればその手段は特に限定されるものではない。炭酸ガスとトウセンダンの抽出物はどちらを先に投与しても、同時に投与してもよい。両者を同時に投与しない場合、両者の投与間隔は、炭酸ガスの角層剥離改善作用の増強効果を奏するかぎり適宜選択しうる。
炭酸ガスとトウセンダンの抽出物を組み合わせてなる剤は、炭酸ガスとトウセンダンの抽出物を配合剤として一の剤型に製剤化したものでも、また単独に製剤化したものを同時に又は間隔を空けて別々に使用できるようにしたキットであってもよい。好ましくは、炭酸ガスとトウセンダンの抽出物を一緒に含む1剤型形態の製剤である。
The means for the stratum corneum peeling improving agent of the present invention is not particularly limited as long as it can supply carbon dioxide gas and an extract of Tosendan to the stratum corneum. Either the carbon dioxide gas or the extract of Tosendan may be administered first, or they may be administered simultaneously. When they are not administered simultaneously, the administration interval between the two may be appropriately selected as long as the effect of enhancing the stratum corneum peeling improving action of carbon dioxide gas is exhibited.
The agent comprising a combination of carbon dioxide gas and an extract of Tosendan ginseng may be a formulation in which carbon dioxide gas and an extract of Tosendan ginseng are combined into a single dosage form, or may be a kit in which the two are individually formulated and used simultaneously or separately at intervals. A single dosage form formulation containing both carbon dioxide gas and an extract of Tosendan ginseng is preferred.
本発明の角層剥離改善剤等としては、好ましくは、噴射剤として炭酸ガスを封入したエアゾール化粧料のような皮膚外用剤(特開2014-129306号公報、特開2017-125003号公報等)、水分と反応して炭酸ガスを発生する炭酸ガス発生剤を含有する発泡性の皮膚外用剤、不織布シート(特開2015-105451号公報)、入浴剤(特開平9-2942号公報、特開2000-191429号公報等)、パッド(特開2006-249025号公報等)等の炭酸ガスを皮膚角層に供給し得る形態の剤であって、さらにトウセンダンの抽出物が配合された剤が挙げられる。なかでも、皮膚外用剤(原液)にトウセンダンの抽出物を含有し、噴射剤として炭酸ガスを封入したエアゾール化粧料のようなエアゾール製剤がより好ましい。 The stratum corneum peeling improving agent of the present invention is preferably an aerosol cosmetic preparation containing carbon dioxide gas as a propellant (JP Patent Publication No. 2014-129306, JP Patent Publication No. 2017-125003, etc.), a foaming cosmetic preparation containing a carbon dioxide gas generator that reacts with moisture to generate carbon dioxide gas, a nonwoven sheet (JP Patent Publication No. 2015-105451), a bath additive (JP Patent Publication No. 9-2942, JP Patent Publication No. 2000-191429, etc.), a pad (JP Patent Publication No. 2006-249025, etc.), etc., which is capable of supplying carbon dioxide gas to the stratum corneum of the skin and further contains an extract of Tosendan. Among them, an aerosol preparation such as an aerosol cosmetic preparation containing an extract of Tosendan and containing carbon dioxide gas as a propellant in an external preparation for skin (undiluted solution) is more preferable.
炭酸ガスを皮膚外用剤に噴射剤として封入する場合、皮膚上において本発明の角層剥離改善効果を得る観点から、噴射剤の総量を基準として、炭酸ガスを90質量%以上含むことが好ましく、95質量%以上含むことがより好ましく、98質量%以上含むことがさらに好ましく、100質量%であることがさらに好ましい。 When carbon dioxide gas is encapsulated as a propellant in a skin topical preparation, from the viewpoint of obtaining the stratum corneum peeling improving effect of the present invention on the skin, it is preferable that the total amount of the propellant contains 90% or more by mass of carbon dioxide gas, more preferably 95% or more by mass, even more preferably 98% or more by mass, and even more preferably 100% by mass.
炭酸ガスを噴射剤として封入したエアゾール製剤を調製する場合における、皮膚外用剤(原液)と炭酸ガスを含む噴射剤の質量割合は、94:6~99.5:0.5が好ましく、95:5~99:1がより好ましく、96.5:3.5~98.5:1.5がさらに好ましい。エアゾール製剤の噴射の形態としては、噴射剤として配合した炭酸ガスを皮膚上に持続的に滞留させる観点から、皮膚外用剤が泡状に吐出されるフォームタイプとするのが好ましい。 When preparing an aerosol formulation containing carbon dioxide gas as a propellant, the mass ratio of the topical skin preparation (undiluted solution) to the propellant containing carbon dioxide gas is preferably 94:6 to 99.5:0.5, more preferably 95:5 to 99:1, and even more preferably 96.5:3.5 to 98.5:1.5. From the viewpoint of allowing the carbon dioxide gas blended as a propellant to remain continuously on the skin, it is preferable for the form of spray of the aerosol formulation to be a foam type in which the topical skin preparation is ejected in the form of a foam.
原液として用いる皮膚外用剤におけるトウセンダンの抽出物の含有量は、皮膚上において炭酸ガスの角層剥離改善作用を増強する観点から、原液中に0.00001質量%以上が好ましく、0.0001質量%以上がより好ましく、0.001質量%以上がさらに好ましく、20質量%以下が好ましく、10質量%以下がより好ましく、5質量%以下がさらに好ましく、1質量%以下がさらに好ましく、0.1質量%以下がさらに好ましく、0.01質量%以下がさらに好ましい。また、トウセンダンの抽出物の含有量は、原液中に0.00001~20質量%が好ましく、0.0001~10質量%がより好ましく、0.001~5質量%がさらに好ましく、0.001~1質量%がさらに好ましく、0.001~0.1質量%がさらに好ましく、0.001~0.01質量%がさらに好ましい。尚、本明細書においてトウセンダンの抽出物の含有量とは、トウセンダンの抽出物の乾燥固形分換算の含有量を意味する。 From the viewpoint of enhancing the stratum corneum peeling improving effect of carbon dioxide gas on the skin, the content of the extract of Tosendan in the undiluted solution is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.001% by mass or more, preferably 20% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, even more preferably 0.1% by mass or less, and even more preferably 0.01% by mass or less. The content of the extract of Tosendan in the undiluted solution is preferably 0.00001 to 20% by mass, more preferably 0.0001 to 10% by mass, even more preferably 0.001 to 5% by mass, even more preferably 0.001 to 1% by mass, even more preferably 0.001 to 0.1% by mass, and even more preferably 0.001 to 0.01% by mass. In this specification, the content of the extract of Tosendan refers to the content of the extract of Tosendan converted into dry solid content.
炭酸ガスを噴射剤として封入するエアゾール製剤(エアゾール化粧料)における炭酸ガスとトウセンダンの抽出物の配合量比(炭酸ガス/トウセンダンの抽出物)は、質量比で600000~0.025が好ましく、より好ましくは5000~0.1、さらに好ましくは3500~0.3、さらに好ましくは2000~1、さらに好ましくは1000~30である。 In an aerosol preparation (aerosol cosmetic) in which carbon dioxide gas is enclosed as a propellant, the ratio of carbon dioxide gas to extract of Tosendan (carbon dioxide gas/extract of Tosendan) is preferably 600,000 to 0.025 by mass, more preferably 5,000 to 0.1, even more preferably 3,500 to 0.3, even more preferably 2,000 to 1, and even more preferably 1,000 to 30.
原液として用いる皮膚外用剤には、さらに化粧料、医薬部外品、医薬品等の皮膚外用剤に通常使用される各種の成分を配合することができる。具体的には、皮膚外用剤を泡状に吐出させ、皮膚における泡ののびを良好とし、使用感に優れ、泡を持続させ炭酸ガスの効果を高める観点から、粉体、油剤、界面活性剤、水溶性増粘剤、水等の成分を含有させることが好ましい。また、通常の化粧料に用いられる成分として、例えば、エタノール、血行促進剤、冷感剤、制汗剤、殺菌剤、美白剤、抗炎症剤、皮膚賦活剤、湿潤剤、保湿剤、防腐剤、酸化防止剤、キレート剤、増粘剤、紫外線吸収剤、乳化安定剤、pH調整剤、色素、香料等も配合することができる。 The skin topical preparation used as the concentrate may further contain various ingredients that are normally used in skin topical preparations such as cosmetics, quasi-drugs, and pharmaceuticals. Specifically, from the viewpoint of discharging the skin topical preparation in a foam form, improving the spread of the foam on the skin, providing an excellent feeling of use, sustaining the foam, and enhancing the effect of carbon dioxide, it is preferable to contain ingredients such as powders, oils, surfactants, water-soluble thickeners, and water. In addition, ingredients that are normally used in cosmetics may also be added, such as ethanol, blood circulation promoters, cooling agents, antiperspirants, disinfectants, whitening agents, anti-inflammatory agents, skin activators, humectants, moisturizers, preservatives, antioxidants, chelating agents, thickeners, UV absorbers, emulsion stabilizers, pH adjusters, colorants, and fragrances.
粉体としては、平均粒子径0.01~30μmを有する酸化ケイ素、酸化チタン、酸化亜鉛、タルク、マイカ、(メタ)アクリル酸又はその塩/(メタ)アクリル酸アルキルクロスポリマー及びシリコーンラストマーから選ばれる1種以上の粉体が挙げられる。上記粉体の中で、本発明においては、特に酸化ケイ素を用いる。本発明で用いる酸化ケイ素は、平均粒径0.25~20μmであり、より良い使用感を与える点から0.25~10μmのものが好ましい。この粉体は、水、アルコール、油剤等には、溶解しないものである。その形状は、球状、板状等いずれでも良い。粉体の内部構造にも制限はなく、多孔質、中空、無孔質等いずれのものも使用することができる。感触の点からは、球状であることが好ましい。なお、本発明において、平均粒径の測定は、レーザー回折散乱式粒子径分布測定装置LA-920/HORIBA/メジアン径で、測定される。 The powder may be one or more powders selected from silicon oxide, titanium oxide, zinc oxide, talc, mica, (meth)acrylic acid or its salt/(meth)acrylic acid alkyl crosspolymer, and silicone lastomer, each having an average particle size of 0.01 to 30 μm. Among the above powders, silicon oxide is particularly used in the present invention. The silicon oxide used in the present invention has an average particle size of 0.25 to 20 μm, and preferably 0.25 to 10 μm in terms of providing a better feeling of use. This powder does not dissolve in water, alcohol, oils, etc. Its shape may be spherical, plate-like, or the like. There is no restriction on the internal structure of the powder, and any of porous, hollow, non-porous, etc. may be used. From the viewpoint of feel, a spherical shape is preferable. In the present invention, the average particle size is measured using a laser diffraction scattering type particle size distribution measuring device LA-920/HORIBA/median size.
本発明で用いる酸化ケイ素は、化粧料に通常用いられるものであれば制限されず、表面を化合物等で処理した改質粉体、シリコーン油、脂肪酸金属塩等を用いた疎水化処理をしていないもの、親水的な表面を有するものを用いて良い。具体的には、市販品としては、サンスフェアNP-30、NP-100、H-31(AGCエスアイテック社 )、サイロピュア35(富士シリシア化学社)、HCS 160M5(池田物産社)等が挙げられる。より良い使用感を与える点から、NP-30がより好ましい。 The silicon oxide used in the present invention is not limited as long as it is one that is commonly used in cosmetics, and may be modified powders whose surfaces have been treated with compounds, those that have not been hydrophobized with silicone oils, fatty acid metal salts, etc., or those with a hydrophilic surface. Specific examples of commercially available products include Sunsphere NP-30, NP-100, and H-31 (AGC Si-Tech Co., Ltd.), Sylopure 35 (Fuji Silysia Chemical Co., Ltd.), and HCS 160M5 (Ikeda Bussan Co., Ltd.). NP-30 is more preferred in terms of providing a better feel when used.
原液における上記粉体の含有量は、炭酸ガスを含有する泡の皮膚への均一な塗布性及び炭酸ガスの皮膚への浸透性を向上させる観点から、原液中に0.001質量%以上が好ましく、0.005質量%以上がより好ましく、0.01質量%以上がさらに好ましく、また2.5質量%以下が好ましく、2.0質量%以下がより好ましく、1.5質量%以下がさらに好ましい。具体的な含有量の範囲は、0.001~2.5質量%が好ましく、0.005~2.0質量%がより好ましく、0.01~1.5質量%がさらに好ましい。 From the viewpoint of improving the uniform application of the foam containing carbon dioxide gas to the skin and the penetration of carbon dioxide gas into the skin, the content of the above powder in the concentrate is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, and preferably 2.5% by mass or less, more preferably 2.0% by mass or less, and even more preferably 1.5% by mass or less. The specific content range is preferably 0.001 to 2.5% by mass, more preferably 0.005 to 2.0% by mass, and even more preferably 0.01 to 1.5% by mass.
油剤としては、通常の化粧料に用いられるものであれば制限されず、例えば、炭化水素油、シリコーン油、エステル油、エーテル油、フッ素油等が挙げられる。より具体的には、例えば、25℃で液状のものとして、メチルポリシロキサン等のシリコーン油類、パラフィン、スクワラン、スクワレン等の炭化水素類;ツバキ油、ホホバ油、オリーブ油、マカデミアナッツ油、アボガド油、オリーブ油等のトリグリセリドを主体とする天然動植物油;グリセリンモノステアリン酸エステル、グリセリンジステアリン酸エステル、グリセリンモノオレイン酸エステル、パルミチン酸イソプロピル、ステアリン酸イソプロピル、ステアリン酸ブチル、ミリスチン酸イソプロピル、フタル酸ジエチル、乳酸ミリスチル、ミリスチン酸セチル、乳酸セチル、2-エチルヘキサン酸セチル、パルミチン酸-2-エチルヘキシル、ミリスチン酸-2-オクチルドデシル、オレイン酸-2-オクチルドデシル、トリイソステアリン酸グリセロール、ジ-パラメトキシケイヒ酸-モノ-2-エチルヘキサン酸グリセリル、イソノナン酸イソトリデシル、モノイソステアリン酸モノミリスチン酸グリセリル、安息香酸アルキル(炭素数12~15のアルキル基)等のモノエステル油;アジピン酸ジイソプロピル、アジピン酸ジイソブチル、ジカプリン酸ネオペンチルグリコール、トリ(カプリル・カプリン酸)グリセリル、トリカプリン酸グリセリン、ジ-2-エチルヘキサン酸ネオペンチルグリコール、ジ(カプリル酸/カプリン酸)プロパンジオール、1-イソステアロイル-3-ミリストイルグリセロール、リンゴ酸ジイソステアリル、N-ラウロイル-L-グルタミン酸ジ(コレステリル・オクチルドデシル)等のジエステル油;アルキル-1,3-ジメチルブチルエーテル、ジカプリリルエーテル、ジカプリリルエーテル等のエーテル油;ユーカリ油、ハッカ油等の精油などが挙げられる。これらのうち、炭酸ガス濃度を高め、なめらかな使用感を付与する点から、モノエステル油、ジエステル油が好ましく、イソノナン酸イソトリデシル、安息香酸アルキルがより好ましい。また、25℃で液状以外の油剤としては、25℃で固体状のワックス、ペーストや固体脂が挙げられ、炭素数12~24の高級アルコール、炭素数12~24の高級脂肪酸、パラフィンワックス等が挙げられる。
油剤の粘度としては、炭酸ガスの皮膚への浸透性を向上させる観点から、1mPa・s以上であり、2mPa・s以上が好ましく、3mPa・s以上がより好ましく、4mPa・s以上がさらに好ましく、100mPa・s以下であり、50mPa・s以下が好ましく、30mPa・s以下がより好ましく、20mPa・s以下がさらに好ましい。また、油剤は、1~100mPa・sのものであり、2~50mPa・sのものが好ましく、3~30mPa・sのものがより好ましく、4~20mPa・sのものがさらに好ましい。
ここで、粘度は、25℃で、BM粘度計(東機産業社製)(ローターNo.1、60rpm、1分)により測定される。
The oil agent is not limited as long as it is one that is commonly used in cosmetics, and examples thereof include hydrocarbon oils, silicone oils, ester oils, ether oils, and fluorine oils. More specifically, examples of liquids at 25° C. include silicone oils such as methylpolysiloxane, hydrocarbons such as paraffin, squalane, and squalene; natural animal and vegetable oils mainly composed of triglycerides such as camellia oil, jojoba oil, olive oil, macadamia nut oil, avocado oil, and olive oil; glycerin monostearate, glycerin distearate, glycerin monooleate, isopropyl palmitate, isopropyl stearate, butyl stearate, isopropyl myristate, diethyl phthalate, myristyl lactate, cetyl myristate, cetyl lactate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, 2-octyldodecyl myristate, 2-octyldodecyl oleate, glycerol triisostearate, di-paramethoxycinnamate-mono-2- Monoester oils such as glyceryl ethylhexanoate, isotridecyl isononanoate, glyceryl monoisostearate monomyristate, and alkyl benzoate (alkyl group having 12 to 15 carbon atoms); diester oils such as diisopropyl adipate, diisobutyl adipate, neopentyl glycol dicaprate, glyceryl tri(capryl-caprate), glycerin tricaprate, neopentyl glycol di-2-ethylhexanoate, di(caprylic acid/capric acid)propanediol, 1-isostearoyl-3-myristoyl glycerol, diisostearyl malate, and di(cholesteryl-octyldodecyl) N-lauroyl-L-glutamate; ether oils such as alkyl-1,3-dimethylbutyl ether, dicaprylyl ether, and dicaprylyl ether; and essential oils such as eucalyptus oil and peppermint oil. Among these, from the viewpoint of increasing the carbon dioxide gas concentration and imparting a smooth feeling of use, monoester oils and diester oils are preferred, and isotridecyl isononanoate and alkyl benzoates are more preferred. Furthermore, examples of oils other than those that are liquid at 25° C. include waxes, pastes and solid fats that are solid at 25° C., such as higher alcohols having 12 to 24 carbon atoms, higher fatty acids having 12 to 24 carbon atoms, and paraffin wax.
From the viewpoint of improving the permeability of carbon dioxide gas into the skin, the viscosity of the oil is 1 mPa·s or more, preferably 2 mPa·s or more, more preferably 3 mPa·s or more, even more preferably 4 mPa·s or more, and 100 mPa·s or less, preferably 50 mPa·s or less, more preferably 30 mPa·s or less, and even more preferably 20 mPa·s or less. The oil has a viscosity of 1 to 100 mPa·s, preferably 2 to 50 mPa·s, more preferably 3 to 30 mPa·s, and even more preferably 4 to 20 mPa·s.
Here, the viscosity is measured at 25° C. using a BM viscometer (manufactured by Toki Sangyo Co., Ltd.) (rotor No. 1, 60 rpm, 1 minute).
油剤は、1種又は2種以上を用いることができ、炭酸ガスの皮膚への浸透性、塗布後の皮膚の皮膜感を向上させる観点から、その含有量は、原液中に1質量%以上であり、2質量%以上が好ましく、4質量%以上がより好ましく、25質量%以下であり、15質量%以下が好ましく、12質量%以下がより好ましい。また、油剤の含有量は、原液中に1~25質量%であり、2~15質量%が好ましく、4~12質量%がさらに好ましい。 One or more types of oils may be used, and from the viewpoint of improving the permeability of carbon dioxide gas into the skin and the film-like feel on the skin after application, the content is 1% by mass or more in the original solution, preferably 2% by mass or more, more preferably 4% by mass or more, 25% by mass or less, preferably 15% by mass or less, and more preferably 12% by mass or less. The content of the oil in the original solution is 1 to 25% by mass, preferably 2 to 15% by mass, and more preferably 4 to 12% by mass.
界面活性剤としては、非イオン界面活性剤、アニオン界面活性剤、カチオン界面活性剤、両性界面活性剤などが挙げられるが、炭酸ガスの原液への溶解量、溶解性促進と塗布時の泡立ち性の観点から、非イオン、アニオン界面活性剤が好ましく用いられる。本発明で使用される非イオン界面活性剤は、HLB3~20の非イオン界面活性剤であり、非イオン界面活性剤のHLBは、泡の皮膚への浸透感、組成物の保存安定性を向上させる観点から、7以上が好ましく、9以上がより好ましく、11以上がさらに好ましく、塗布後の皮膚の皮膜感を向上させる観点から、18以下が好ましく、16以下がより好ましく、15以下がさらに好ましい。また、非イオン界面活性剤のHLBは、7~18が好ましく、9~16がより好ましく、11~15がさらに好ましい。
ここで、HLB(親水性-親油性のバランス〈Hydrophilic-Lypophilic Balance〉)とは、界面活性剤の全分子量に占める親水基部分の分子量を示すものであり、グリフィン(Griffin)の式により求められるものである。2種以上の非イオン界面活性剤から構成される混合界面活性剤のHLBは、各非イオン界面活性剤のHLB値をその配合比率に基づいて相加算平均することにより求められる。
Examples of the surfactant include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants, but nonionic and anionic surfactants are preferably used from the viewpoints of the amount of carbon dioxide gas dissolved in the original solution, promotion of solubility, and foaming property during application. The nonionic surfactant used in the present invention is a nonionic surfactant with an HLB of 3 to 20. The HLB of the nonionic surfactant is preferably 7 or more, more preferably 9 or more, and even more preferably 11 or more from the viewpoints of improving the penetration feeling of the foam into the skin and the storage stability of the composition, and is preferably 18 or less, more preferably 16 or less, and even more preferably 15 or less from the viewpoint of improving the film feeling on the skin after application. The HLB of the nonionic surfactant is preferably 7 to 18, more preferably 9 to 16, and even more preferably 11 to 15.
Here, HLB (hydrophilic-lipophilic balance) indicates the molecular weight of the hydrophilic group portion in the total molecular weight of the surfactant, and is calculated by Griffin's formula. The HLB of a mixed surfactant composed of two or more nonionic surfactants is calculated by averaging the HLB values of each nonionic surfactant based on their blending ratio.
具体的な非イオン界面活性剤としては、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ポリオキシエチレン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレンアルキルエーテル、ポリオキシエチレン硬化ヒマシ油等が挙げられ、ポリグリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油が好ましく、ソルビタン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油がより好ましく、ポリオキシエチレン硬化ヒマシ油がさらに好ましい。
ポリオキシエチレン硬化ヒマシ油は、炭酸ガスの皮膚への浸透性、泡の安定性を向上させる観点から、エチレンオキサイドの平均付加モル数が、20~90であるのが好ましく、30~80がより好ましく、50~70がさらに好ましい。
Specific examples of the nonionic surfactant include sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oil, and the like. Polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene hydrogenated castor oil are preferred, sorbitan fatty acid esters and polyoxyethylene hydrogenated castor oil are more preferred, and polyoxyethylene hydrogenated castor oil is even more preferred.
From the viewpoint of improving the permeability of carbon dioxide gas into the skin and the foam stability, the polyoxyethylene hydrogenated castor oil preferably has an average added mole number of ethylene oxide of 20 to 90, more preferably 30 to 80, and even more preferably 50 to 70.
非イオン界面活性剤は、1種又は2種以上を組み合わせて用いることができ、その含有量は、泡ののび、炭酸ガスの皮膚への浸透性、塗布後の皮膚の皮膜感を向上させる観点から、原液中に0.05質量%以上であり、0.1質量%以上が好ましく、0.3質量%以上がより好ましく、6質量%以下であり、2質量%以下が好ましく、1質量%以下がより好ましい。また、非イオン界面活性剤の含有量は、原液中に0.05~6質量%であり、0.1~2質量%が好ましく、0.3~1質量%がより好ましい。 The nonionic surfactant may be used alone or in combination of two or more kinds, and the content thereof in the concentrate is 0.05% by mass or more, preferably 0.1% by mass or more, more preferably 0.3% by mass or more, 6% by mass or less, preferably 2% by mass or less, and more preferably 1% by mass or less, from the viewpoint of improving the spread of the foam, the permeability of the carbon dioxide gas into the skin, and the film-like feel on the skin after application. The content of the nonionic surfactant in the concentrate is 0.05 to 6% by mass, preferably 0.1 to 2% by mass, and more preferably 0.3 to 1% by mass.
水溶性増粘剤としては、通常の化粧料に用いられるものであれば良く、例えば、カラギーナン、デキストリン、メチルセルロース、エチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ポリビニルアルコール、ポリアクリル酸、ポリメタクリル酸、カルボキシビニルポリマー、(アクリル酸/アクリル酸アルキル(C10-30))コポリマー、キサンタンガム、カルボキシメチルキチン、キトサン等が挙げられる。これらのうち、炭酸ガスの揮散抑制、原液の安定性、塗布時及び塗布後の使用感(べたつきのなさ、なめらかさ及びやわらかさ付与)の点から、アクリル酸系ポリマーが好ましく、カルボキシビニルポリマー、アクリル酸/アクリル酸アルキルコポリマーがより好ましく、(アクリル酸/アクリル酸アルキル(C10-30))コポリマーがより好ましい。ここで、(アクリル酸/アクリル酸アルキル(C10-30))コポリマーとは、C10-30アルキルアクリル酸とアクリル酸、メタクリル酸又はこれらの低級アルキルエステルとの共重合体であって、ショ糖のアリルエーテル又はペンタエリスリトールのアリルエーテルで架橋したものであり、ペムレンTR-1、ペムレンTR-2、カーボポールETD2020、カーボポール1342、カーボポール1382(以上、Lubrizol AdvancedMaterials 社)等の市販品を用いることができる。また、ポリアクリル酸、カルボキシビニルポリマー、(アクリル酸/アクリル酸アルキル(C10-30))コポリマーなどの酸型の水溶性増粘剤は、水酸化カリウム、水酸化ナトリウム等のアルカリ金属水酸化物を中和剤として用い、水溶性ないし水分散性の塩として用いるのが好ましい。 The water-soluble thickener may be any one that is commonly used in cosmetics, such as carrageenan, dextrin, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, carboxyvinyl polymer, (acrylic acid/alkyl acrylate (C10-30)) copolymer, xanthan gum, carboxymethyl chitin, chitosan, etc. Of these, from the standpoints of suppressing the evaporation of carbon dioxide gas, the stability of the original solution, and the feel during and after application (non-stickiness, smoothness, and softness), acrylic acid-based polymers are preferred, with carboxyvinyl polymers and acrylic acid/alkyl acrylate copolymers being more preferred, and (acrylic acid/alkyl acrylate (C10-30)) copolymers being more preferred. Here, the (acrylic acid/alkyl acrylate (C10-30)) copolymer is a copolymer of C10-30 alkyl acrylic acid and acrylic acid, methacrylic acid or lower alkyl esters thereof, crosslinked with an allyl ether of sucrose or an allyl ether of pentaerythritol, and commercially available products such as Pemulen TR-1, Pemulen TR-2, Carbopol ETD2020, Carbopol 1342, and Carbopol 1382 (all from Lubrizol Advanced Materials) can be used. In addition, it is preferable to use an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide as a neutralizing agent for an acid-type water-soluble thickener such as polyacrylic acid, carboxyvinyl polymer, or (acrylic acid/alkyl acrylate (C10-30)) copolymer, as a water-soluble or water-dispersible salt.
水溶性増粘剤は、上記から選ばれる1種又は2種以上を組み合わせて用いることができ、その含有量は、塗布時のべたつきのなさ、原液の安定性を向上させる点から、原液中に0.05質量%以上であり、0.1質量%以上が好ましく、0.2質量%以上がより好ましく、1質量%以下であり、0.8質量%以下が好ましく、0.7質量%以下がより好ましい。また、水溶性増粘剤の含有量は、原液中に0.05~1質量%であり、0.1~0.8質量%が好ましく、0.2~0.7質量%がより好ましい。 The water-soluble thickener may be used alone or in combination of two or more selected from the above, and the content thereof in the stock solution is 0.05% by mass or more, preferably 0.1% by mass or more, more preferably 0.2% by mass or more, and 1% by mass or less, preferably 0.8% by mass or less, and more preferably 0.7% by mass or less, from the viewpoint of improving the non-stickiness during application and the stability of the stock solution. The content of the water-soluble thickener in the stock solution is 0.05 to 1% by mass, preferably 0.1 to 0.8% by mass, and more preferably 0.2 to 0.7% by mass.
水は、溶媒として働き、原液中に、55質量%以上が好ましく、60質量%以上がより好ましく、65質量%以上がさらに好ましく、95質量%以下が好ましく、93質量%以下がより好ましく、90質量%以下がさらに好ましい。また、水の含有量は、原液中に、55~95質量%が好ましく、60~93質量%がより好ましく、65~90質量%がさらに好ましい。 Water acts as a solvent, and is present in the stock solution at a content of preferably 55% by mass or more, more preferably 60% by mass or more, even more preferably 65% by mass or more, preferably 95% by mass or less, more preferably 93% by mass or less, and even more preferably 90% by mass or less. The water content in the stock solution is preferably 55 to 95% by mass, more preferably 60 to 93% by mass, and even more preferably 65 to 90% by mass.
原液は、安定性、泡の吐出性、炭酸ガスの皮膚への浸透性を向上させる観点から、25℃における粘度が、500mPa・s以上であるのが好ましく、1000mPa・s以上がより好ましく、1500mPa・s以上がさらに好ましく、20000mPa・s以下が好ましく、15000mPa・s以下がより好ましく、10000mPa・s以下がさらに好ましい。原液は、25℃における粘度が、500~20000mPa・sであるのが好ましく、1000~15000mPa・sがより好ましく、1500~10000mPa・sがさらに好ましい。
ここで、粘度は、25℃で、BM粘度計(東機産業社製)を用いて、ローターNo.3、12rpm、1分で測定し、粘度が10000mPa・sを超えた場合は、ローターNo.3、6rpm、1分で測定した値である。
From the viewpoint of improving stability, foam ejection, and carbon dioxide gas permeability into the skin, the viscosity of the concentrate at 25° C. is preferably 500 mPa·s or more, more preferably 1000 mPa·s or more, and even more preferably 1500 mPa·s or more, and is preferably 20000 mPa·s or less, more preferably 15000 mPa·s or less, and even more preferably 10000 mPa·s or less. The viscosity of the concentrate at 25° C. is preferably 500 to 20000 mPa·s, more preferably 1000 to 15000 mPa·s, and even more preferably 1500 to 10000 mPa·s.
Here, the viscosity is measured at 25° C. using a BM viscometer (manufactured by Toki Sangyo Co., Ltd.) with rotor No. 3 at 12 rpm for 1 minute, and when the viscosity exceeds 10,000 mPa·s, the value is measured with rotor No. 3 at 6 rpm for 1 minute.
発泡性皮膚外用剤において用いられる炭酸ガス発生剤としては、通常、炭酸ガス発生物質と酸性物質からなり、水と接触することにより両者が反応し、炭酸ガスを発生する製剤が挙げられる。
ここで、酸性物質としては、無機酸、有機酸のいずれでもよく、これらの1種又は2種以上が用いられる。有機酸としては、例えば、コハク酸、フマル酸、リンゴ酸、アジピン酸、酒石酸、安息香酸、クエン酸、ピロリドンカルボン酸、サリチル酸から選ばれる1種又は2種以上が挙げられる。また、無機酸としては、具体的には、例えば、リン酸、ホウ酸、メタケイ酸及び無水ケイ酸から選ばれる1種又は2種以上が挙げられる。なかでも、炭酸ガス発生量を確保する観点から、有機酸が好ましく、クエン酸、リンゴ酸、フマル酸、コハク酸、及び酒石酸から選ばれる1種又は2種以上であることがより好ましく、クエン酸、リンゴ酸及びフマル酸から選ばれる1種又は2種であることがさらに好ましい。
The carbon dioxide gas generating agent used in the foaming skin preparation for external use is usually a preparation which comprises a carbon dioxide gas generating substance and an acidic substance, and which reacts with water to generate carbon dioxide gas.
Here, the acidic substance may be either an inorganic acid or an organic acid, and one or more of these may be used. The organic acid may be, for example, one or more selected from succinic acid, fumaric acid, malic acid, adipic acid, tartaric acid, benzoic acid, citric acid, pyrrolidone carboxylic acid, and salicylic acid. In addition, the inorganic acid may be, for example, one or more selected from phosphoric acid, boric acid, metasilicic acid, and silicic anhydride. Among them, from the viewpoint of ensuring the amount of carbon dioxide gas generated, organic acids are preferred, and one or more selected from citric acid, malic acid, fumaric acid, succinic acid, and tartaric acid are more preferred, and one or two selected from citric acid, malic acid, and fumaric acid are even more preferred.
炭酸ガス発生物質としては、炭酸塩が挙げられ、具体的には、例えば、炭酸ナトリウム、炭酸水素ナトリウム、炭酸カリウム、炭酸水素カリウム、炭酸カルシウム、炭酸マグネシウム、及びセスキ炭酸ナトリウムから選ばれる1種又は2種以上が挙げられる。なかでも、炭酸塩としては、炭酸ガス発生量を確保する観点から、炭酸ナトリウム及び炭酸水素ナトリウムから選ばれる1種又は2種以上であることが好ましい。 Carbon dioxide gas generating substances include carbonates, and specifically include, for example, one or more selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate, magnesium carbonate, and sodium sesquicarbonate. Among them, from the viewpoint of ensuring the amount of carbon dioxide gas generated, it is preferable that the carbonate is one or more selected from sodium carbonate and sodium bicarbonate.
斯かる炭酸ガス発生剤は、酸性物質、炭酸ガス発生物質を同一剤に含んでいてもよく、また複数の剤に分けて含有していてもよい。 Such carbon dioxide gas generating agents may contain the acidic substance and the carbon dioxide gas generating substance in the same agent, or may contain them separately in multiple agents.
発泡性皮膚外用剤におけるトウセンダンの抽出物の含有量は、皮膚上において炭酸ガスの角層剥離改善作用を増強する観点から、組成物全量中に0.00001質量%以上が好ましく、0.0001質量%以上がより好ましく、0.001質量%以上がさらに好ましく、20質量%以下が好ましく、10質量%以下がより好ましく、5質量%以下がさらに好ましく、1質量%以下がさらに好ましく、0.1質量%以下がさらに好ましく、0.01質量%以下がさらに好ましい。また、トウセンダンの抽出物の含有量は、組成物全量中に0.00001~20質量%が好ましく、0.0001~10質量%がより好ましく、0.001~5質量%がさらに好ましく、0.001~1質量%がさらに好ましく、0.001~0.1質量%がさらに好ましく、0.001~0.01質量%がさらに好ましい。 The content of the extract of Tosendan in the foaming skin topical preparation is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.001% by mass or more, preferably 20% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, even more preferably 0.1% by mass or less, and even more preferably 0.01% by mass or less. The content of the extract of Tosendan is preferably 0.00001 to 20% by mass, more preferably 0.0001 to 10% by mass, even more preferably 0.001 to 5% by mass, even more preferably 0.001 to 1% by mass, even more preferably 0.001 to 0.1% by mass, and even more preferably 0.001 to 0.01% by mass.
発泡性皮膚外用剤の剤形は、固形状、液体状、ジェル状等いずれでもよい。固形状の場合、顆粒状、細粒状、粉末状であり得る。当該皮膚外用剤は、化粧料、医薬部外品、医薬品のいずれの形態でもよいが、化粧品又は医薬部外品として用いることが好ましい。具体的には、化粧水、乳液、美容ジェル、パック料、育毛料、洗顔料、クレンジング料、シャンプー、コンディショナー等、様々な形態を挙げることができ、使用に際し、手のひらの上あるいは容器内で含水物質と混合し、発泡させて使用する態様が好ましい。 The foaming topical skin preparation may be in any form, such as a solid, liquid, or gel. If it is solid, it may be in the form of granules, fine particles, or powder. The topical skin preparation may be in the form of a cosmetic, quasi-drug, or pharmaceutical, but is preferably used as a cosmetic or quasi-drug. Specifically, it may be in various forms, such as a lotion, milky lotion, beauty gel, pack, hair growth product, facial cleanser, cleansing product, shampoo, and conditioner. When used, it is preferable to mix it with a water-containing substance on the palm of the hand or in a container and foam it.
不織布シートとしては、粉体である炭酸ガス発生剤(酸性物質及び炭酸ガス発生物質)及びトウセンダンの抽出物を担持し、皮膚に貼付した不織布シートに水や湯をかけるのみで、シートを貼付した皮膚上において十分な量の炭酸ガスを発生させ、十分な量のトウセンダンの抽出物を供給することができるシートが挙げられる。
具体的には、(A)有機酸及び無機酸から選ばれる粉体、(B)炭酸塩である粉体、(C)融点が50℃以上110℃以下であり、かつ25℃で固体である物質(例えば、ポリエチレングリコール等のポリエーテルやヒドロキシエチルセルロース等のセルロース誘導体のような高分子化合物;ミリスチン酸、パルミチン酸等の高級脂肪酸;セチルアルコール、ヘキサデシルアルコール、セテアリルアルコール、ステアリルアルコール等の高級アルコール;グルコース、マルトース等の糖類)、及び(D)繊維を含有する不織布シート(特開2015-105451号公報)にトウセンダンの抽出物がさらに配合された不織布シートが挙げられる。
An example of a nonwoven fabric sheet is a sheet that carries a powdered carbon dioxide gas generating agent (an acidic substance and a carbon dioxide gas generating substance) and an extract of Tosendan, and that can generate a sufficient amount of carbon dioxide gas on the skin where the sheet is attached and supply a sufficient amount of Tosendan extract by simply pouring water or hot water onto the nonwoven fabric sheet attached to the skin.
Specific examples of the present invention include (A) a powder selected from organic acids and inorganic acids, (B) a powder which is a carbonate, (C) a substance having a melting point of 50° C. or more and 110° C. or less and which is solid at 25° C. (for example, polymeric compounds such as polyethers such as polyethylene glycol and cellulose derivatives such as hydroxyethyl cellulose; higher fatty acids such as myristic acid and palmitic acid; higher alcohols such as cetyl alcohol, hexadecyl alcohol, cetearyl alcohol, and stearyl alcohol; and sugars such as glucose and maltose), and (D) a nonwoven fabric sheet containing fibers (JP Patent Publication No. 2015-105451 A) further containing an extract of Tosendan.
トウセンダンの抽出物の含有量は、皮膚上において炭酸ガスの角層剥離改善作用を増強する観点から、不織布シート1m2あたり、0.000005g以上が好ましく、0.00005g以上がより好ましく、0.0005g以上がさらに好ましく、200g以下が好ましく、100g以下がより好ましく、50g以下がさらに好ましく、10g以下がさらに好ましく、1g以下がさらに好ましく、0.1g以下がさらに好ましい。また、トウセンダンの抽出物の含有量は、不織布シート1m2あたり、0.000005~200gが好ましく、0.00005~100gがより好ましく、0.0005~50gがさらに好ましく、0.00005~10gさらに好ましく、0.00005~1gがさらに好ましく、0.00005~0.1gがさらに好ましい。 From the viewpoint of enhancing the stratum corneum peeling improving effect of carbon dioxide gas on the skin, the content of the extract of Tosendan is preferably 0.000005g or more, more preferably 0.00005g or more, even more preferably 0.0005g or more, and preferably 200g or less, more preferably 100g or less, even more preferably 50g or less, even more preferably 10g or less, even more preferably 1g or less, and even more preferably 0.1g or less per 1m2 of nonwoven fabric sheet. Also, the content of the extract of Tosendan is preferably 0.000005 to 200g, more preferably 0.00005 to 100g, even more preferably 0.0005 to 50g, even more preferably 0.00005 to 10g, even more preferably 0.00005 to 1g, and even more preferably 0.00005 to 0.1g per 1m2 of nonwoven fabric sheet.
入浴剤としては、(a)界面活性剤を10重量%以上及び炭酸塩を該界面活性剤の2重量倍以上含む固体状賦形物、(b)炭酸塩又は炭酸水素塩、(c)有機酸を含有し、成分(a)の含有量が入浴剤中3~20重量%である発泡性錠剤型入浴剤(特開平9-2942号公報)にトウセンダンの抽出物がさらに配合された発泡性錠剤型入浴剤や、(A)常温で固体の酸又は水に溶解したときに酸性を示す無機物、(B)炭酸塩、(C)冷感剤又は温感剤を含有する発泡性化粧料(特開2000-191429号公報)にトウセンダンの抽出物がさらに配合された発泡性化粧料が挙げられる。 Examples of bath additives include effervescent tablet-type bath additives (JP Patent Publication No. 9-2942) that contain (a) a solid excipient containing 10% by weight or more of a surfactant and at least twice the weight of the surfactant in carbonate, (b) a carbonate or bicarbonate, and (c) an organic acid, and in which the content of component (a) in the bath additive is 3 to 20% by weight (A), and further contain an extract of Tosendan, and effervescent cosmetic products (JP Patent Publication No. 2000-191429) that contain (A) an inorganic substance that is acidic when dissolved in a solid acid or water at room temperature, (B) a carbonate, and (C) a cooling or warming agent, and further contain an extract of Tosendan.
トウセンダンの抽出物の含有量は、皮膚上において炭酸ガスの角層剥離改善作用を増強する観点から、組成物全量中に0.00001重量%以上が好ましく、0.0001重量%以上がより好ましく、0.001重量%以上がさらに好ましく、20重量%以下が好ましく、10重量%以下がより好ましく、5重量%以下がさらに好ましく、1質量%以下がさらに好ましく、0.1質量%以下がさらに好ましく、0.01質量%以下がさらに好ましい。また、トウセンダンの抽出物の含有量は、組成物全量中に0.00001~20重量%が好ましく、0.0001~10重量%がより好ましく、0.001~5重量%がさらに好ましく、0.001~1質量%がさらに好ましく、0.001~0.1質量%がさらに好ましく、0.001~0.01質量%がさらに好ましい。 From the viewpoint of enhancing the stratum corneum peeling improving effect of carbon dioxide gas on the skin, the content of the extract of Tosendan is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, even more preferably 0.001% by weight or more, preferably 20% by weight or less, more preferably 10% by weight or less, even more preferably 5% by weight or less, even more preferably 1% by weight or less, even more preferably 0.1% by weight or less, and even more preferably 0.01% by weight or less. The content of the extract of Tosendan is preferably 0.00001 to 20% by weight, more preferably 0.0001 to 10% by weight, even more preferably 0.001 to 5% by weight, even more preferably 0.001 to 1% by weight, even more preferably 0.001 to 0.1% by weight, and even more preferably 0.001 to 0.01% by weight.
パッドとしては、吸水性を有する基底層と、該基底層を被覆するように設けられたガスバリア性を有する保護層と、該保護層と前記基底層の間に封入された、炭酸ガス発生剤を含んでなり、保護層の周縁部分で皮膚に貼着できるようにされたパッド(特開2006-249025号公報)の炭酸ガス発生剤にトウセンダンの抽出物がさらに配合されたパッドが挙げられる。 The pad is made of a water-absorbent base layer, a protective layer with gas barrier properties that is provided to cover the base layer, and a carbon dioxide gas generating agent enclosed between the protective layer and the base layer, and is designed to be attached to the skin at the periphery of the protective layer (JP Patent Publication No. 2006-249025), and an extract of Tosendan is further blended into the carbon dioxide gas generating agent.
本発明の炭酸ガスの角層剥離改善作用の増強剤等は、トウセンダンの抽出物を皮膚角層に供給できるものであればその手段は特に限定されるものではない。本発明の炭酸ガスの角層剥離改善作用の増強剤等は、炭酸ガスの投与に先立って投与しても、炭酸ガスと同時に投与しても、炭酸ガスの投与後に投与してもよい。本発明の炭酸ガスの角層剥離改善作用の増強剤等と炭酸ガスを同時に投与しない場合、両者の投与間隔は、本発明の炭酸ガスの角層剥離改善作用の増強剤等の効果を奏するかぎり適宜選択しうる。 The means for the enhancer of the stratum corneum delamination-improving effect of carbon dioxide gas of the present invention is not particularly limited as long as it can supply the extract of Tosendan to the stratum corneum of the skin. The enhancer of the stratum corneum delamination-improving effect of carbon dioxide gas of the present invention may be administered prior to, simultaneously with, or after the administration of carbon dioxide gas. When the enhancer of the stratum corneum delamination-improving effect of carbon dioxide gas of the present invention and carbon dioxide gas are not administered simultaneously, the administration interval between the two may be appropriately selected as long as the effect of the enhancer of the stratum corneum delamination-improving effect of carbon dioxide gas of the present invention is exhibited.
本発明の炭酸ガスの角層剥離改善作用の増強剤等の投与形態としては、固形、半固形又は液状であり得、好ましくは皮膚外用剤、貼付剤等による非経口投与形態である。より好ましくは皮膚外用剤である。剤形としては、軟膏剤、クリーム剤、ゲル剤、貼付剤、チック剤、リニメント剤、ローション剤、スプレー剤等が挙げられる。
このような種々の剤形の製剤は、有効成分であるトウセンダンの抽出物を、必要に応じて、薬学的に又は化粧料に許容される担体、その他の薬効成分又は化粧成分と適宜組み合わせて、それぞれ一般的な製造方法により調製することができる。当該薬学的に又は化粧料に許容される担体としては、例えば、水、油剤、界面活性剤、溶剤、増粘剤、ゲル化剤、アルコール、キレート剤、乳化安定剤、pH調節剤、塩類、防腐剤、酸化防止剤、紫外線吸収剤、色素、香料等が挙げられる。また、その他の薬効成分又は化粧成分としては、例えば、植物抽出物、保湿剤、抗菌剤、抗炎症剤、清涼剤、メークアップ成分等が挙げられる。
The administration form of the enhancer of the stratum corneum peeling improving effect of carbon dioxide gas of the present invention may be solid, semi-solid or liquid, and is preferably a parenteral administration form such as a skin topical preparation or patch. More preferably, it is a skin topical preparation. Dosage forms include ointments, creams, gels, patches, ticks, liniments, lotions, sprays, etc.
Such preparations in various dosage forms can be prepared by appropriately combining the active ingredient, an extract of Tosendan, with a pharmaceutical or cosmetically acceptable carrier, or other medicinal or cosmetic ingredients, as necessary, by a general manufacturing method. Examples of the pharmaceutical or cosmetically acceptable carrier include water, oils, surfactants, solvents, thickeners, gelling agents, alcohols, chelating agents, emulsion stabilizers, pH regulators, salts, preservatives, antioxidants, ultraviolet absorbers, pigments, fragrances, etc. Examples of other medicinal or cosmetic ingredients include plant extracts, moisturizers, antibacterial agents, anti-inflammatory agents, cooling agents, makeup ingredients, etc.
上記製剤中のトウセンダンの抽出物の含有量は、その使用形態により異なるが、皮膚上において炭酸ガスの角層剥離改善作用を増強する観点から、0.00001質量%以上が好ましく、0.0001質量%以上がより好ましく、0.001質量%以上がさらに好ましく、20質量%以下が好ましく、10質量%以下がより好ましく、5質量%以下がさらに好ましく、1質量%以下がさらに好ましく、0.1質量%以下がさらに好ましく、0.01質量%以下がさらに好ましい。また、トウセンダンの抽出物の含有量は、上記製剤中に0.00001~20質量%が好ましく、0.0001~10質量%がより好ましく、0.001~5質量%がさらに好ましく、0.001~1質量%がさらに好ましく、0.001~0.1質量%がさらに好ましく、0.001~0.01質量%がさらに好ましい。 The content of the extract of Tosendan in the above preparation varies depending on the form of use, but from the viewpoint of enhancing the stratum corneum peeling improving effect of carbon dioxide gas on the skin, it is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.001% by mass or more, preferably 20% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, even more preferably 0.1% by mass or less, and even more preferably 0.01% by mass or less. The content of the extract of Tosendan in the above preparation is preferably 0.00001 to 20% by mass, more preferably 0.0001 to 10% by mass, even more preferably 0.001 to 5% by mass, even more preferably 0.001 to 1% by mass, even more preferably 0.001 to 0.1% by mass, and even more preferably 0.001 to 0.01% by mass.
本発明の角層剥離改善剤等又は炭酸ガスの角層剥離改善作用の増強剤等は、任意の適用計画に従って、皮膚に噴霧、塗布等の方法で適用され得るが、1日1回~数回に分け、適用され得る。適用期間は適宜決定することができ、例えば、1日以上が好ましく、7日以上がより好ましく、14日以上がさらに好ましい。 The stratum corneum peeling improving agent, etc., or the agent for enhancing the stratum corneum peeling improving effect of carbon dioxide gas, etc., of the present invention can be applied to the skin by spraying, painting, etc., according to any application plan, and can be applied once to several times a day. The application period can be appropriately determined, and is, for example, preferably one day or more, more preferably seven days or more, and even more preferably 14 days or more.
本発明の角層剥離改善剤等の適用対象としては、それを必要としていれば特に限定されないが、角層剥離の正常化を目的とするヒト、肌の質感の改善を必要とするヒト、肌の質感の改善を希望するヒト等が挙げられる。 The subjects for which the stratum corneum peeling improving agent of the present invention can be used are not particularly limited as long as they are in need of it, and examples of such subjects include people who aim to normalize stratum corneum peeling, people who need to improve their skin texture, and people who wish to improve their skin texture.
実施例1 コルネオデスモソーム分解亢進作用
(1)表皮モデルの調製
トウセンダン抽出物、炭酸ガス、及びこれらの併用が皮膚の角層剥離機能に与える効果を、ヒト正常表皮細胞を重層培養したヒト3次元培養表皮モデルであるLabCyte EPI-MODEL12 6D(J-TEC)を用いて検証した。LabCyte EPI-MODEL12 6Dに付属の培地1.0mLを培養カップの外側に添加し、37℃、5%CO2インキュベータ内にて24時間、静置培養した。
Example 1 Corneodesmosome Degradation Enhancement Effect (1) Preparation of Epidermal Model The effects of the extract of Tosendan, carbon dioxide, and their combined use on the stratum corneum delaminating function of the skin were examined using LabCyte EPI-MODEL12 6D (J-TEC), a human 3-dimensional cultured epidermal model in which normal human epidermal cells were cultured in a layered manner. 1.0 mL of the medium provided with LabCyte EPI-MODEL12 6D was added to the outside of the culture cup, and the cells were statically cultured for 24 hours in a 37°C, 5% CO2 incubator.
(2)トウセンダン抽出物の添加、炭酸ガス製剤の塗布
トウセンダン抽出物として、トウセンダンの乾燥果実(川楝子)のエタノール抽出物(乾燥固形分)を0.5質量%、1,3-ブチレングリコールを79.75質量%、精製水を19.75質量%含有するトウセンダン抽出液を使用した。トウセンダン抽出物の対照として、1,3-ブチレングリコール79.75質量%、精製水20.25質量%を含有する溶媒(以下、対照溶媒)を調製した。
(2) Addition of the extract of Tosendan and application of the carbon dioxide gas preparation As the extract of Tosendan, an extract of Tosendan containing 0.5% by mass of ethanol extract (dry solid content) of the dried fruit of Tosendan (Kawasaki), 79.75% by mass of 1,3-butylene glycol, and 19.75% by mass of purified water was used. As a control for the Tosendan extract, a solvent containing 79.75% by mass of 1,3-butylene glycol and 20.25% by mass of purified water (hereinafter referred to as the control solvent) was prepared.
炭酸ガス製剤とその対照(炭酸ガス非含有製剤)の組成を下記表1に示す。全ての原料は、60℃の温度下で原料を攪拌させながら混合した。まず、メッキンス-Mとリン酸2水素カリウム、適量の精製水を混合し、攪拌した。次に、PEMULEN TR-1を混合し、攪拌した。これに、液体苛性カリ(48%)と精製水を適宜混合し、攪拌した。さらに、エマノーンCH60(K)と精製水の残りを全て混合し、攪拌した。これを下記表1中に示す原液とした。これに、炭酸ガスを封入したものを炭酸ガス製剤とし(原液と炭酸ガスの比は、97.8:2.2)、炭酸ガスを封入しなかったものを炭酸ガス非含有製剤とした(原液のみ)。 The compositions of the carbon dioxide gas preparation and its control (formulation not containing carbon dioxide gas) are shown in Table 1 below. All raw materials were mixed at a temperature of 60°C while stirring the raw materials. First, Mekxun-M, potassium dihydrogen phosphate, and an appropriate amount of purified water were mixed and stirred. Next, PEMULEN TR-1 was mixed and stirred. To this, liquid caustic potash (48%) and purified water were appropriately mixed and stirred. Furthermore, all of the remaining Emmanon CH60 (K) and purified water were mixed and stirred. This was the stock solution shown in Table 1 below. Carbon dioxide gas was enclosed in this to make the carbon dioxide gas preparation (the ratio of stock solution to carbon dioxide gas was 97.8:2.2), and to the one without carbon dioxide gas enclosed was the non-carbon dioxide gas-containing preparation (stock solution only).
本試験では、以下に示す4群で試験を実施した。
コントロール群:トウセンダン抽出物非適用(対照溶媒適用)且つ炭酸ガス非適用(炭酸ガス非含有製剤適用)
トウセンダン抽出物群:トウセンダン抽出物適用且つ炭酸ガス非適用(炭酸ガス非含有製剤適用)
炭酸ガス群:トウセンダン抽出物非適用(対照溶媒適用)且つ炭酸ガス適用(炭酸ガス含有製剤適用)
併用群:トウセンダン抽出物適用且つ炭酸ガス適用(炭酸ガス含有製剤適用)
まず、付属の培地に前記のトウセンダン抽出液を終濃度が0.3%となるように添加してトウセンダン抽出物含有培地を調製した(トウセンダン抽出物の終濃度0.0015%、乾燥固形分換算)。トウセンダン抽出物非適用については、付属の培地に対照溶媒を終濃度が0.3%となるように添加して対照溶媒含有培地を調製した。次に、LabCyte EPI-MODEL12 6Dの培養カップの外側の培地を除去し、調製したトウセンダン抽出物含有培地もしくは対照溶媒含有培地1.0mLを添加した。これを37℃、5%CO2インキュベータ内に戻し、48時間静置培養した。培養後、培養カップ内側の表皮モデル表面に炭酸ガス含有製剤もしくは炭酸ガス非含有製剤0.5gを塗布した。その後、これを37℃、5%CO2インキュベータ内で、2時間静置培養した。
This study was conducted in the following four groups.
Control group: No application of Tosendan extract (control solvent application) and no application of carbon dioxide (non-carbon dioxide-containing formulation application)
Tosendan extract group: Tosendan extract and no carbon dioxide gas (non-carbon dioxide gas-containing formulation)
Carbon dioxide group: No use of Tosendan extract (control solvent) and use of carbon dioxide (use of carbon dioxide-containing preparation)
Combination group: Use of Tosendan extract and carbon dioxide gas (use of carbon dioxide gas-containing preparation)
First, the extract of Tosendan was added to the attached medium so that the final concentration was 0.3% to prepare a medium containing Tosendan extract (final concentration of Tosendan extract: 0.0015%, calculated as dry solids). For non-application of Tosendan extract, a control solvent was added to the attached medium so that the final concentration was 0.3% to prepare a control solvent-containing medium. Next, the medium on the outside of the culture cup of LabCyte EPI-MODEL12 6D was removed, and 1.0 mL of the prepared Tosendan extract-containing medium or control solvent-containing medium was added. This was returned to a 37°C, 5% CO2 incubator and cultured stationary for 48 hours. After culture, 0.5 g of a carbon dioxide-containing formulation or a carbon dioxide-free formulation was applied to the surface of the epidermis model inside the culture cup. Then, this was cultured stationary for 2 hours in a 37°C, 5% CO2 incubator.
(3)切片の作製
炭酸ガス含有製剤もしくは炭酸ガス非含有製剤を塗布して2時間静置培養した後、表皮モデルを回収し、O.C.T.コンパウンド(サクラファインテックジャパン製)に包埋して凍結ブロックを作製した。凍結ブロックは5μm厚に薄切し、スライドグラスに貼付した。
(3) Preparation of slices After applying the carbon dioxide-containing or non-carbon dioxide-containing formulation and statically culturing for 2 hours, the epidermis model was collected and embedded in O.C.T. compound (Sakura Finetech Japan) to prepare a frozen block. The frozen block was sliced to a thickness of 5 μm and attached to a slide glass.
(4)抗DSG1抗体を用いた免疫染色
スライドグラスを4%パラホルムアルデヒド・りん酸緩衝液(富士フイルム和光純薬製)100mLに10分間浸漬して組織を固定した。続いて、0.05% Tween(登録商標)-20/PBS(PBS-T)溶液100mL中にスライドグラスを5分間浸漬し、これを3回繰り返して洗浄した。
切片のブロッキング処理を行うために、スライドグラスを湿潤箱(モイストチャンバー、アズワン製)に並べて、ブロッキング液(1%ウシ血清アルブミン/PBS-T溶液)100μLを切片に滴下し、30分間静置した。30分後、ブロッキング液を除去し、ブロッキング液で10倍希釈した抗Desmoglein1抗体(Progen Biotechnik.製,#651110)50μLを切片に滴下して、4℃で一晩反応させた(1次抗体反応)。翌日、PBS-T溶液100mL中にスライドグラスを5分間浸漬し、これを3回繰り返して洗浄した。洗浄後、スライドグラスを湿潤箱に並べて、ブロッキング液で100倍希釈した蛍光標識した抗マウス抗体(Jackson製,#715-095-151)50μLを切片に滴下し、37℃で30分間反応させた(2次抗体反応)。その後、PBS-T溶液100mL中にスライドグラスを5分間浸漬し、これを3回繰り返して洗浄し、カバーガラスを被せて封入した。切片の観察は、共焦点レーザー顕微鏡(LSM710,カールツァイス製)を用いて画像を撮影した。
(4) Immunostaining using anti-DSG1 antibody The slide glass was immersed in 100 mL of 4% paraformaldehyde phosphate buffer (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) for 10 minutes to fix the tissue. The slide glass was then immersed in 100 mL of 0.05% Tween (registered trademark)-20/PBS (PBS-T) solution for 5 minutes, and washed three times.
To perform blocking treatment of the sections, the slide glass was arranged in a moist chamber (moist chamber, manufactured by AS ONE), 100 μL of blocking solution (1% bovine serum albumin/PBS-T solution) was dropped onto the sections, and the sections were left to stand for 30 minutes. After 30 minutes, the blocking solution was removed, and 50 μL of anti-Desmoglein 1 antibody (manufactured by Progen Biotechnik., #651110) diluted 10-fold with the blocking solution was dropped onto the sections, and reacted overnight at 4° C. (primary antibody reaction). The next day, the slide glass was immersed in 100 mL of PBS-T solution for 5 minutes, and this was repeated three times for washing. After washing, the slides were arranged in a wet box, and 50 μL of fluorescently labeled anti-mouse antibody (Jackson, #715-095-151) diluted 100-fold with blocking solution was dropped onto the sections, and reacted at 37° C. for 30 minutes (secondary antibody reaction). The slides were then immersed in 100 mL of PBS-T solution for 5 minutes, washed three times, and covered with a cover glass for sealing. Images of the sections were taken using a confocal laser microscope (LSM710, Carl Zeiss).
(5)DSG1シグナルの計測
ImageJ(ver.1.53C)を用いて、以下の方法によりDSG1シグナルを算出した。まず、取得した画像中の薄切組織底面の長さを計測した。次に、表皮モデル全体の総輝度を算出した。表皮モデル全体の総輝度を薄切組織底面の長さで除した値(総輝度(-)/薄切組織底面の長さ(μm))をDSG1シグナルとした。コントロール群のDSG1シグナルを1としたとき、各群のDSG1シグナルの相対値を算出し、トウセンダン抽出物、炭酸ガス含有組成物、及びこれらの併用が表皮モデル中のDSG1発現に与える効果を検証した。
(5) Measurement of DSG1 signal Using ImageJ (ver.1.53C), the DSG1 signal was calculated by the following method. First, the length of the bottom surface of the thin-sectioned tissue in the acquired image was measured. Next, the total brightness of the entire epidermal model was calculated. The total brightness of the entire epidermal model divided by the length of the bottom surface of the thin-sectioned tissue (total brightness (-)/length of the bottom surface of the thin-sectioned tissue (μm)) was used as the DSG1 signal. When the DSG1 signal of the control group was set to 1, the relative value of the DSG1 signal of each group was calculated, and the effect of the Tosendan extract, the carbon dioxide-containing composition, and their combined use on DSG1 expression in the epidermal model was examined.
(6)結果
図1に各群の抗DSG1抗体を用いた免疫染色画像を、図2に各群のDSG1シグナル強度を、コントロール群を1とする相対値で示す。図1に示すように、コントロール群において観察されたDSG1の蛍光発色部分(表皮中の白色部分)は、トウセンダン抽出物群ではほとんど変化は見られなかったが、炭酸ガス群では白色部分の減少が観察され、炭酸ガスとトウセンダン抽出物の併用群ではその減少はさらに顕著であった。この結果はDSG1の蛍光発色を計測した結果にも反映されており、図2に示すように炭酸ガスとトウセンダン抽出物の併用により、有意にDSG1シグナルが減衰した。本結果から、トウセンダン抽出物は、単独ではDSG1分解促進作用を示さないものの、炭酸ガスと併用することで炭酸ガスのDSG1分解促進作用を亢進したと考えられる。
(6) Results Figure 1 shows the immunostaining images using anti-DSG1 antibodies for each group, and Figure 2 shows the DSG1 signal intensity for each group, relative to the control group being 1. As shown in Figure 1, the fluorescent coloring portion of DSG1 observed in the control group (white portion in the epidermis) was almost unchanged in the Tosendan extract group, but a decrease in the white portion was observed in the carbon dioxide group, and the decrease was even more significant in the group in which carbon dioxide and Tosendan extract were used in combination. This result is also reflected in the results of measuring the fluorescent coloring of DSG1, and as shown in Figure 2, the DSG1 signal was significantly attenuated by the combined use of carbon dioxide and Tosendan extract. From this result, it is considered that Tosendan extract alone does not exhibit DSG1 decomposition promoting action, but when used in combination with carbon dioxide, it enhances the DSG1 decomposition promoting action of carbon dioxide.
実施例2 肌の質感改善効果(ヒト試験)
(1)評価方法
20~59歳の健常女性18名を試験参加者とし、2週間、毎日朝夜の2回、化粧水の塗布前に、トウセンダン抽出物として実施例1のトウセンダン抽出液を1%含有する原液(トウセンダン抽出物の終濃度0.005%、乾燥固形分換算)に炭酸ガスを封入した炭酸製剤(原液と炭酸ガスの比は、97.8:2.2)約1g(吐出時直径3cm)を顔全体に塗布させた。その後の肌ケアは普段通りとした。
Example 2: Effect of improving skin texture (human test)
(1) Evaluation method Eighteen healthy women aged 20 to 59 years were selected as test participants, and for two weeks, twice a day, morning and night, before applying lotion, about 1 g (3 cm in diameter when discharged) of a carbonic acid preparation (ratio of original solution to carbon dioxide gas: 97.8:2.2) containing 1% of the Tosendan extract of Example 1 as Tosendan extract (final concentration of Tosendan extract: 0.005%, calculated as dry solid content) was applied to the entire face. Thereafter, skin care was carried out as usual.
試験期間終了後、試験期間開始前と比べた肌の質感の改善度についてのアンケートをとり、なめらかさ、しっとり感、柔らかさを評価項目として、「肌がなめらかになった」、「肌がしっとりした」、「肌が柔らかくなった」という点について、どのように感じたかを以下の5つからいずれかを選択してもらい、全試験参加者のアンケート結果を集計して肌の質感の改善度を評価した。 After the trial period ended, participants were asked to complete a questionnaire regarding the degree of improvement in skin texture compared to before the trial began. The evaluation items were smoothness, moistness, and softness, and participants were asked to select one of the following five options regarding how they felt about "skin has become smoother," "skin has become moist," or "skin has become softer." The survey results of all trial participants were compiled to evaluate the degree of improvement in skin texture.
1:そう思う(改善した)
2:ややそう思う(少し改善した)
3:どちらともいえない
4:あまりそう思わない(少し悪化した)
5:そう思わない(悪化した)
1: I think so (improved)
2: I think so (somewhat improved)
3: I can't say either way 4: I don't really think so (it's gotten a little worse)
5: I don't think so (it's gotten worse)
結果を表2に示す。炭酸ガスとトウセンダン抽出物の適用により、9割以上の試験者がいずれの評価項目においても肌の質感の改善効果を実感しており(1又は2を選択)、特に肌のなめらかさの改善に優れていた。本結果から、炭酸ガスとトウセンダン抽出物の併用により角層剥離が改善され、肌の質感が改善したものと考えられる。 The results are shown in Table 2. By applying carbon dioxide gas and Tosendan extract, over 90% of the test subjects felt that the application had an improved effect on skin texture in all evaluation items (selecting 1 or 2), with particularly excellent improvement in skin smoothness. From these results, it is believed that the combined use of carbon dioxide gas and Tosendan extract improved stratum corneum peeling, improving skin texture.
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