JP6022333B2 - Ceramide production promoter - Google Patents
Ceramide production promoter Download PDFInfo
- Publication number
- JP6022333B2 JP6022333B2 JP2012270388A JP2012270388A JP6022333B2 JP 6022333 B2 JP6022333 B2 JP 6022333B2 JP 2012270388 A JP2012270388 A JP 2012270388A JP 2012270388 A JP2012270388 A JP 2012270388A JP 6022333 B2 JP6022333 B2 JP 6022333B2
- Authority
- JP
- Japan
- Prior art keywords
- extract
- prevention
- skin
- ceramide
- agent
- 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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Landscapes
- Cosmetics (AREA)
- Medicines Containing Plant Substances (AREA)
Description
本発明は、セラミド産生促進剤及び保湿剤に関する。 The present invention relates to a ceramide production promoter and a humectant.
スフィンゴ脂質の一つであるセラミドは、生体全体の中では微量であるが、皮膚の最も外側の層である角層中では、脂質成分の半分以上を占め、皮膚の保湿機構、バリア機構に重要な役割を果たしている。セラミドは、表皮細胞中において産生・分泌された後に角層中の細胞間においてラメラ構造を構築する。乾燥肌、荒れ肌、アトピー性皮膚炎、老人性乾皮症、乾癬等の皮膚疾患においては、セラミドの健全な代謝が妨げられ、角層中のセラミド量が減少し、皮膚の保湿能やバリア能の低下等を引き起こしていることが数多く報告されている。
表皮細胞におけるセラミド産生を亢進し、角層中のセラミド量を増加させることができれば、皮膚の保湿能やバリア能を高めることができ、角層中のセラミド量低下に伴う皮膚疾患、例えば、乾燥肌、荒れ肌、アトピー性皮膚炎、老人性乾皮症、乾癬等、の予防・改善等に有用であると考えられる。例えば、ユーカリ抽出物は、表皮細胞のセラミド産生を亢進し、角層中のセラミド量を増加させることで、皮膚の保湿能・バリア能を高めることが知られている（非特許文献１）。これまでに、減少したセラミドを外部から補給することもが試みられているが、現在のところ必ずしもその効果は十分なものではない。
Ceramide, one of the sphingolipids, is a trace amount in the whole organism, but in the stratum corneum, the outermost layer of the skin, occupies more than half of the lipid component and is important for the skin moisturizing and barrier mechanisms Plays an important role. Ceramide builds a lamellar structure between cells in the stratum corneum after being produced and secreted in epidermal cells. In skin diseases such as dry skin, rough skin, atopic dermatitis, senile psoriasis and psoriasis, the healthy metabolism of ceramide is impeded, and the amount of ceramide in the stratum corneum is reduced, so that the skin's moisturizing ability and barrier ability It has been reported a lot that causes the decrease of
If ceramide production in epidermal cells is enhanced and the amount of ceramide in the stratum corneum can be increased, the skin's moisturizing ability and barrier ability can be increased, and skin diseases associated with decreased ceramide amount in the stratum corneum, such as It is considered useful for the prevention and improvement of skin, rough skin, atopic dermatitis, senile psoriasis, psoriasis and the like. For example, eucalyptus extract is known to enhance skin moisturizing ability and barrier ability by increasing ceramide production in epidermal cells and increasing the amount of ceramide in the stratum corneum (Non-patent Document 1). Up to now, attempts have been made to replenish the reduced ceramide from the outside, but the effect is not necessarily sufficient at present.
本発明は、高いセラミド産生促進効果を有するセラミド産生促進剤を提供することを課題とする。また、本発明は、セラミド産生を促進する作用に優れた保湿剤を提供することを課題とする。 An object of the present invention is to provide a ceramide production promoter having a high ceramide production promotion effect. Moreover, this invention makes it a subject to provide the moisturizer excellent in the effect | action which accelerates | stimulates ceramide production.
本発明者等は上記課題に鑑み、鋭意検討を行った。その結果、シベリアトウヒ（Picea obovata）の植物抽出物が高いセラミド産生促進作用を有することを見出し、これらが新規の保湿成分として有用であるとの知見を得た。本発明はこの知見に基づき完成されたものである。 In view of the above problems, the present inventors have conducted intensive studies. As a result, the plant extract of Siberian spruce ( Picea obovata ) was found to have a high ceramide production promoting action, and it was found that these were useful as novel moisturizing ingredients. The present invention has been completed based on this finding.
すなわち、本発明は、シベリアトウヒ（Picea obovata）の抽出物を有効成分として含有するセラミド産生促進剤に関する。
また、本発明は、シベリアトウヒ（Picea obovata）の抽出物を有効成分として含有する保湿剤に関する。
That is, this invention relates to the ceramide production promoter which contains the extract of Siberian spruce ( Picea obovata ) as an active ingredient.
The present invention also relates to a humectant containing an extract of Picea obovata as an active ingredient.
本発明によれば、高いセラミド産生促進効果を有するセラミド産生促進剤を提供することができる。また、本発明によれば、セラミド産生促進作用に優れた保湿剤を提供することができる。 ADVANTAGE OF THE INVENTION According to this invention, the ceramide production promoter which has a high ceramide production promotion effect can be provided. Moreover, according to this invention, the moisturizing agent excellent in the ceramide production promotion effect can be provided.
本発明のセラミド産生促進剤及び保湿剤は、シベリアトウヒ（Picea obovata）の抽出物を含有する。後述の実施例で実証するように、この植物抽出物は高いセラミド産生促進効果を奏する。
シベリアトウヒ（Picea obovata）は、マツ科（Pinaceae）のトウヒ属（Picea）に属する植物で、一般的な建築用木材や製紙用材として、また、葉はスプルースビールの製造に使われている。
The ceramide production promoter and humectant of the present invention contain an extract of Siberian spruce ( Picea obovata ). As will be demonstrated in the examples described later, this plant extract exhibits a high ceramide production promoting effect.
Siberian spruce ( Picea obovata ) is a plant belonging to the genus Picea of the Pinaceae family, and is used for general construction wood and papermaking, and leaves are used for the production of spruce beer.
本発明で用いる抽出物は、シベリアトウヒの全木、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）を用いて抽出することができる。また、各部位を複数組み合わせて用いてもよい。なかでも、葉を用いて抽出された葉抽出物を用いることが好ましい。
上記の植物は生のままで抽出に用いてもよく、抽出効率を高めるために、乾燥、細断、粉砕等の処理を施したものを用いることも好ましい。
The extract used in the present invention is a whole tree of Siberian spruce, or any part (root, rhizome, trunk, branch, stem, leaf, bark, sap, resin, flower, fruit, seed, peel, bud, bud, spike , Heartwood, etc.). Moreover, you may use combining each site | part in multiple numbers. Especially, it is preferable to use the leaf extract extracted using the leaf.
The above plants may be used as they are in the raw state, and it is also preferable to use those subjected to treatments such as drying, shredding, and pulverization in order to increase extraction efficiency.
シベリアトウヒの抽出物を得る方法については特に限定はなく、上記植物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、上記植物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抽出物として用いることができる。また、これらの抽出物、水蒸気蒸留物、圧搾物等を、単独或いは２種以上組み合わせたものを抽出物として用いてもよい。 The method for obtaining the extract of Siberian spruce is not particularly limited, and the extract can be obtained by extracting the above-mentioned plant by a usual method. Specifically, dried products obtained by drying the above plants, squeezed juice obtained by squeezing and extracting the pulverized products, steam distillates, crude extracts using various extraction solvents, distribution of crude extracts, column chromatography, etc. Extract fractions obtained by purification by various chromatographic methods can be used as the extract in the present invention. Moreover, you may use what combined these extract, steam distillate, pressing material, etc. individually or in combination of 2 or more types as an extract.
本発明においては、シベリアトウヒ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い。
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。抽出溶剤の例としては、水；アルコール（例えば、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、エチレングリコール、プロピレングリコール、ブチレングリコール等の多価アルコール）；アセトン、メチルエチルケトン等のケトン；酢酸メチル、酢酸エチル等のエステル；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；ポリエチレングリコール等のポリエーテル；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；ヘキサン、シクロヘキサン、石油エーテル等の炭化水素；ベンゼン、トルエン等の芳香族炭化水素；ピリジン；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。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もできる。なかでも、水、アルコール、及び当該アルコールの水溶液から選ばれる少なくとも１種を用いることが好ましく、水、エタノール水溶液、プロピレングリコール、及びブチレングリコールから選ばれる少なくとも１種を用いることがより好ましく、水、又はエタノール水溶液を用いることがさらに好ましく、エタノール水溶液を用いることがよりさらに好ましい。
In the present invention, it is more preferable to use an extract obtained by using an extraction solvent from a dried product obtained by drying Siberian spruce or a pulverized product thereof.
As the extraction solvent, either a polar solvent or a nonpolar solvent can be used, and these can also be mixed and used. Examples of the extraction solvent include water; alcohol (for example, monohydric alcohols such as methanol, ethanol, propanol, and butanol, polyhydric alcohols such as ethylene glycol, propylene glycol, and butylene glycol); ketones such as acetone and methyl ethyl ketone; methyl acetate Esters such as ethyl acetate; Chain 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; pyridine; supercritical carbon dioxide; fats and oils, waxes, and other oils. A mixture in which two or more of the above solvents are combined can also be used as the extraction solvent. Among them, it is preferable to use at least one selected from water, an alcohol, and an aqueous solution of the alcohol, more preferably at least one selected from water, an aqueous ethanol solution, propylene glycol, and butylene glycol. Or it is more preferable to use ethanol aqueous solution, and it is still more preferable to use ethanol aqueous solution.
抽出溶剤として用いるアルコール水溶液の濃度は、５容量％以上が好ましく、３０容量％以上がより好ましく、４０容量％以上がさらに好ましい。濃度の上限については特に制限はないが、９９容量％以下が実際的である。アルコール水溶液の濃度は、５容量％以上９９容量％以下が好ましく、３０容量％以上９９容量％以下がより好ましく、４０容量％以上９９容量％以下がさらに好ましい。
特に、抽出溶剤として用いるエタノール水溶液の濃度は、３０容量％以上が好ましく、４０容量％以上であることがより好ましく、５０容量％以上がさらに好ましい。また、濃度の上限については特に制限はないが、９９容量％以下が好ましく、９５容量％以下がより好ましい。アルコール水溶液の濃度は、３０容量％以上９９容量％以下が好ましく、４０容量％以上９９容量％以下がより好ましく、４０容量％以上９５容量％以下がさらに好ましく、５０容量％以上９５容量％以下がよりさらに好ましい。
The concentration of the aqueous alcohol solution used as the extraction solvent is preferably 5% by volume or more, more preferably 30% by volume or more, and still more preferably 40% by volume or more. The upper limit of the concentration is not particularly limited, but 99% by volume or less is practical. The concentration of the alcohol aqueous solution is preferably 5% by volume to 99% by volume, more preferably 30% by volume to 99% by volume, and still more preferably 40% by volume to 99% by volume.
In particular, the concentration of the aqueous ethanol solution used as the extraction solvent is preferably 30% by volume or more, more preferably 40% by volume or more, and even more preferably 50% by volume or more. The upper limit of the concentration is not particularly limited, but is preferably 99% by volume or less, and more preferably 95% by volume or less. The concentration of the aqueous alcohol solution is preferably 30% to 99% by volume, more preferably 40% to 99% by volume, more preferably 40% to 95% by volume, and more preferably 50% to 95% by volume. Even more preferred.
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、アルコール類又はアルコール水溶液を用いて抽出する場合、下記条件で、浸漬又は加熱還流するのが好ましい。溶剤は、植物１質量部に対して１質量部以上用いることが好ましく、５０質量部以下用いることが好ましい。抽出温度は、３℃以上が好ましく、２０℃以上がより好ましく、１００℃以下が好ましく、８０℃以下がより好ましい。抽出時間は、１時間以上が好ましく、１日以上がより好ましく、数週間以下が好ましく、３０日間以下がより好ましい。また、抽出効率を上げる為、併せて攪拌を行ったり、溶剤中でホモジナイズ処理を行ってもよい。 The extraction conditions vary depending on the solvent used and are not particularly limited. For example, when extraction is performed using water, alcohols or an aqueous alcohol solution, it is preferably immersed or heated to reflux under the following conditions. The solvent is preferably used in an amount of 1 part by mass or more, preferably 50 parts by mass or less, based on 1 part by mass of the plant. The extraction temperature is preferably 3 ° C. or higher, more preferably 20 ° C. or higher, preferably 100 ° C. or lower, and more preferably 80 ° C. or lower. The extraction time is preferably 1 hour or longer, more preferably 1 day or longer, several weeks or shorter, more preferably 30 days or shorter. Moreover, in order to raise extraction efficiency, you may stir together or you may perform a homogenization process in a solvent.
上記溶媒で抽出して得られた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。本発明で用いるシベリアトウヒ抽出物は、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 obtained by extraction with the above solvent may be used as it is, but it is also possible to fractionate and use a fraction having high activity by an appropriate separation means such as gel filtration, chromatography, precision distillation, etc. it can. The Siberian spruce extract used in the present invention includes the various extracts thus obtained, a diluted solution thereof, a concentrated solution thereof, a purified product thereof or a dry powder thereof.
後述の実施例に示すように、シベリアトウヒの抽出物は優れたセラミド産生促進作用を有する。前述のように、セラミドは皮膚の保湿機構やバリア機構において重要な役割を担っており、セラミド産生の促進は、生体の有するセラミド産生機構を健常化し、減少した角層中のセラミドを増加させ、高いバリア機能及び保湿機能を有する皮膚を取り戻すことにつながる。すなわち、シベリアトウヒの抽出物は、セラミド産生を促進させるため、ひいては皮膚の保湿機能やバリア機能を維持、改善、健常化するために使用することができる。
上記使用は、治療的使用（即ち医療行為）であっても非治療的使用（非医療的な行為）であってもよい。また、上記使用の対象は、ヒト、非ヒト動物、又はそれらに由来する検体であり得る。なお、前記「非治療的」とは、医療行為、すなわち治療による人体への処理行為を含まない概念である。
As shown in Examples described later, the extract of Siberian spruce has an excellent ceramide production promoting action. As described above, ceramide plays an important role in the skin moisturizing mechanism and barrier mechanism, and promotion of ceramide production normalizes the ceramide production mechanism of the living body, increases ceramide in the reduced stratum corneum, It leads to regaining skin having high barrier function and moisturizing function. That is, the extract of Siberian spruce can be used to promote ceramide production, and thus maintain, improve, and normalize the skin moisturizing function and barrier function.
The use may be a therapeutic use (ie medical practice) or a non-therapeutic use (non-medical practice). Moreover, the subject of the use can be a human, a non-human animal, or a specimen derived therefrom. The “non-therapeutic” is a concept that does not include a medical action, that is, a treatment action on the human body by treatment.
シベリアトウヒの抽出物を有効成分として含有するセラミド産生促進剤又は保湿剤は、上記使用の具体的態様の１つであり、治療的用途（医療用途）、非治療用途（非医療用途）のいずれにも適用することができる。その使用形態も、人や動物の皮膚、爪、粘膜、毛髪等に適用されうるすべての形態が含まれる。
具体的には、医薬品、医薬部外品、化粧料等としての使用が挙げられ、化粧料や医薬部外品、医薬品の場合は皮膚外用剤の形態で、医薬品の場合は投与形態で、使用することができる。また、これらの剤は、各種の飲食品やペットフード等に有効成分として配合することもできる。
A ceramide production promoter or moisturizer containing an extract of Siberian spruce as an active ingredient is one of the specific embodiments of the above-mentioned use. It can also be applied to. The usage forms include all forms that can be applied to human, animal skin, nails, mucous membranes, hair and the like.
Specific examples include use as pharmaceuticals, quasi-drugs, cosmetics, etc., in the case of cosmetics, quasi-drugs, and pharmaceuticals, in the form of external skin preparations, and in the case of pharmaceuticals, in the dosage form can do. Moreover, these agents can also be mix | blended as an active ingredient in various food-drinks, pet food, etc.
本発明のセラミド産生促進剤又は保湿剤は、有効成分であるシベリアトウヒの抽出物のみを含有するものであってもよいし、効果に影響を与えない範囲で他の成分を含有するものであってもよい。
有効成分以外の他の成分は、剤の形態や用途等に応じて適宜選択できる。例えば、剤として成形しやすいよう、酸化チタン、炭酸カルシウム、蒸留水、乳糖、デンプン等の適当な液体または固体の賦形剤または増量剤を加えてもよい。また、他の薬効成分（その他の美白剤、保湿剤など）、酸化防止剤、紫外線吸収剤、界面活性剤、増粘剤、色材種等を加えてもよい。
他の薬効成分としては、例えば、既知のセラミド産生促進剤、擬似セラミド、天然セラミド、糖セラミド等の保湿剤が挙げられる。また、保湿剤以外の薬効成分として、皮膚老化防止剤、美白剤等が挙げられる。
既知のセラミド産生促進剤としては、例えば、アセチルヒドロキシプロリン、グリチルリチン酸カリウム、Ｌ-カルニチン、アスコルビン酸、アスコルビルグルコシド、アスコルビルリン酸マグネシウム、dl-α-トコフェリル-dl-アスコルビルリン酸、dl-α-トコフェリルリン酸、ニコチン酸アミド、ニコチン酸トコフェロール、L-乳酸、ビタミンＣ、アスパラガス抽出物、ブッチャーブルーム、ゲンクワニン、ローズマリー、ラベンダー、セージ、ナツメ、黒（赤）霊芝、トウキ、クジン、ヨクイニン、ベニセアンヌ抽出物、ライスパワーエキスなどが挙げられる。
擬似セラミドとしては、例えば、市販のセラミドＲ（ユニリーバ製）、セラミドＰＣ-１０４（太平洋化学製）、セラミドＨＯ３（sederma製）、エルデュウＰＳ-２０３（味の素製）などが挙げられる。
糖セラミドとしては、例えば、グルコシルセラミド、ガラクトシルセラミド等が挙げられ、市販のものとしては、ニップンセラミド（日本製粉製）、オリザセラミド（オリザ油化製）、ニッサンセラミド、ネオリキッドセラミドN（日本油脂製）、セラミド（ユニチカ製）等が挙げられる。
The ceramide production promoter or moisturizer of the present invention may contain only an extract of Siberian spruce, which is an active ingredient, or it may contain other ingredients within a range that does not affect the effect. May be.
Components other than the active ingredient can be appropriately selected according to the form and use of the agent. For example, an appropriate liquid or solid excipient or extender such as titanium oxide, calcium carbonate, distilled water, lactose, starch or the like may be added so as to facilitate forming as an agent. In addition, other medicinal components (other whitening agents, moisturizers, etc.), antioxidants, ultraviolet absorbers, surfactants, thickeners, colorant types, and the like may be added.
Examples of other medicinal ingredients include humectants such as known ceramide production promoters, pseudoceramides, natural ceramides, and sugar ceramides. Examples of medicinal ingredients other than the humectant include skin aging inhibitors and whitening agents.
Known ceramide production promoters include, for example, acetylhydroxyproline, potassium glycyrrhizinate, L-carnitine, ascorbic acid, ascorbyl glucoside, magnesium ascorbyl phosphate, dl-α-tocopheryl-dl-ascorbyl phosphate, dl-α- Tocopheryl phosphate, nicotinamide, tocopherol nicotinate, L-lactic acid, vitamin C, asparagus extract, butcher bloom, genquanine, rosemary, lavender, sage, jujube, black (red) ganoderma, toki, kujin, Yokuinin, Beniceanne extract, rice power extract and the like.
Examples of the pseudo ceramide include commercially available ceramide R (manufactured by Unilever), ceramide PC-104 (manufactured by Taiheiyo Kagaku), ceramide HO3 (manufactured by sederma), and Erdew PS-203 (manufactured by Ajinomoto).
Examples of sugar ceramides include glucosyl ceramide, galactosyl ceramide, etc., and commercially available products include nippon ceramide (manufactured by Nippon Flour), oryzah ceramide (manufactured by Oriza Yoka), Nissan ceramide, neo-liquid ceramide N (Japanese fat and oil). Manufactured), ceramide (manufactured by Unitika) and the like.
剤に他の成分を配合する場合、有効成分であるシベリアトウヒ抽出物の含有量は特に制限されないが、上記抽出物が剤中に固形分濃度（固形分換算）で、０．００００１質量％以上含まれることが好ましく、０．０００１質量％以上含まれることがより好ましい。また、上記抽出物が剤中に固形分濃度で、２０質量％以下含まれることが好ましく、１０質量％以下含まれることがより好ましい。さらに、上記抽出物が剤中に固形分濃度で、０．００００１質量％以上２０質量％以下含まれることが好ましく、０．０００１質量％以上１０質量％以下含まれることがより好ましい。 When other ingredients are added to the agent, the content of the active Siberian spruce extract is not particularly limited, but the extract is 0.00001% by mass or more in terms of solid concentration (in terms of solid content) in the agent. It is preferably contained, and more preferably 0.0001% by mass or more. Moreover, it is preferable that 20 mass% or less of the said extract is contained by solid content concentration in an agent, and it is more preferable that 10 mass% or less is contained. Furthermore, it is preferable that the said extract is 0.00001 mass% or more and 20 mass% or less by solid content concentration in an agent, and it is more preferable that 0.0001 mass% or more and 10 mass% or less are contained.
本発明のセラミド産生促進剤又は保湿剤を皮膚外用剤の形態で使用する場合、当該「皮膚外用剤」には、皮膚化粧料、外用医薬品、外用医薬部外品等として皮膚に適用されるものが含まれ、その剤型も水溶液系、可溶化系、乳化系、粉末系、ゲル系、軟膏系、クリーム、水−油２層系、水−油−粉末３層系など、幅広い形態をとり得る。より具体的には、洗顔料、化粧水、ローション、乳液、クリーム、ジェル、エッセンス（美容液）、パック、マスク、マッサージ剤、ファンデーション、口紅、入浴剤、シャンプー、ヘアコンディショナー、ヘアトニック、軟膏、ペースト、シート状製品（サニタリー用品等の吸収性物品、おしり拭き、ウェットティッシュ等）等の形態が挙げられる。
また、これらの剤型とするにあたって、各種油剤、界面活性剤、ゲル化剤、防腐剤、酸化防止剤、溶剤、アルコール、水、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、香料等を適宜配合することができる。
When the ceramide production promoter or moisturizer of the present invention is used in the form of a skin external preparation, the “skin external preparation” is applied to the skin as a skin cosmetic, an external medicine, an external quasi-drug, etc. The dosage form can take a wide variety of forms such as aqueous solution, solubilization system, emulsification system, powder system, gel system, ointment system, cream, water-oil two-layer system, water-oil-powder three-layer system. obtain. More specifically, facial cleanser, lotion, lotion, milky lotion, cream, gel, essence (beauty serum), pack, mask, massage agent, foundation, lipstick, bath preparation, shampoo, hair conditioner, hair tonic, ointment, Examples include pastes, sheet-like products (absorbent articles such as sanitary products, wiping wipes, wet tissues, etc.).
In addition, in making these dosage forms, various oil agents, surfactants, gelling agents, preservatives, antioxidants, solvents, alcohol, water, chelating agents, thickeners, ultraviolet absorbers, emulsion stabilizers, pH A regulator, a pigment, a fragrance, and the like can be appropriately blended.
本発明のセラミド産生促進剤又は保湿剤を医薬品としてヒトや動物に投与する形態で使用する場合、例えば、錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤等の経口用固形製剤、内服液剤、シロップ剤等の経口用液体製剤、注射剤、外用剤、坐剤、経皮吸収剤等の非経口用製剤などの形態とすることができる。
これらの製剤を調製するに際しては、賦形剤、結合剤、増量剤、崩壊剤、界面活性剤、滑沢剤、分散剤、緩衝剤、保存剤、嬌味剤、香料、被膜剤、担体、希釈剤等を適宜配合することができる。
When the ceramide production promoter or moisturizer of the present invention is used as a pharmaceutical in the form of administration to humans or animals, for example, oral solid preparations such as tablets, coated tablets, granules, powders, capsules, oral liquids, syrups It can be in the form of oral liquid preparations such as pills, parenteral preparations such as injections, external preparations, suppositories, and transdermal absorption agents.
In preparing these preparations, excipients, binders, extenders, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, Diluents and the like can be appropriately blended.
本発明のセラミド産生促進剤又は保湿剤を飲食品、ペットフード等に有効成分として配合する場合、一般飲食品の他、皮膚の保湿能又はバリア機能の改善・維持効果をコンセプトとし、必要に応じてその旨を表示した健康飲食品、美容飲食品、特定保健用飲食品、病者用飲食品等等の機能性飲食品に添加、配合することができる。
飲食品等の種類に特に制限はなく、例えば、果汁飲料、乳飲料、茶系飲料等の飲料類、キャンディ、ドロップ、ゼリー、クッキー、チョコレート、ケーキ、ヨーグルト、ガム等の菓子類、調味料、調理油、乳製品、パン類、麺類、加工米等が挙げられる。また、錠剤（タブレット）、カプセル、顆粒、シロップ等の美容食品、健康食品等としてもよい。
When formulating the ceramide production promoter or moisturizer of the present invention as an active ingredient in foods and drinks, pet food, etc. It can be added to and blended with functional foods and beverages such as health foods and beverages, beauty foods and beverages, health foods and beverages for specified health use, foods and beverages for the sick, and the like.
There is no particular limitation on the type of food and drink, for example, beverages such as fruit juice beverages, milk beverages, tea-based beverages, confectionery such as candy, drop, jelly, cookies, chocolate, cakes, yogurt, gum, seasonings, Examples include cooking oil, dairy products, breads, noodles, and processed rice. Moreover, it is good also as beauty foods, health foods, etc., such as a tablet (tablet), a capsule, a granule, and syrup.
本発明のセラミド産生促進剤又は保湿剤の成人１人当たりの１日の使用量は、剤中の有効成分の含有量、適用対象者の状態、体重、性別、年齢等の条件により異なるが、通常、シベリアトウヒの抽出物を乾燥固形分換算で、０．００１ｍｇ以上使用することが好ましく、０．０１ｍｇ以上使用することがより好ましい。また、前記植物の抽出物を乾燥固形分換算で、１０００ｍｇ以下使用することが好ましく、１００ｍｇ以下使用することがより好ましい。さらに、前記植物の抽出物を乾燥固形分換算で、０．００１ｍｇ以上１０００ｍｇ以下使用することが好ましく、０．０１ｍｇ以上１００ｍｇ以下使用することがより好ましい。 The daily use amount of the ceramide production promoter or moisturizing agent of the present invention per adult varies depending on the content of the active ingredient in the agent, the condition of the application subject, body weight, sex, age, etc. The extract of Siberian spruce is preferably used in an amount of 0.001 mg or more, more preferably 0.01 mg or more in terms of dry solid content. The plant extract is preferably used in an amount of 1000 mg or less, more preferably 100 mg or less in terms of dry solid content. Further, the plant extract is preferably used in an amount of 0.001 mg to 1000 mg, more preferably 0.01 mg to 100 mg in terms of dry solid content.
本発明のセラミド産生促進剤及び保湿剤は、表皮細胞におけるセラミド産生を亢進し、角層中のセラミド量を増加させることで、皮膚の保湿機能やバリア機能を高めることができる。この作用により、本発明のセラミド産生促進剤及び保湿剤は、角層中のセラミド量低下によって引き起こされる皮膚疾患、例えば、乾燥肌、荒れ肌、アトピー性皮膚炎、老人性乾皮症、乾癬等を予防、緩和、改善することができる。この観点から、本発明のセラミド産生促進剤及び保湿剤は、皮膚のバリア機能向上剤、乾燥肌予防剤又は改善剤、荒れ肌予防剤又は改善剤、アトピー性皮膚炎予防剤又は改善剤、老人性乾皮症予防剤又は改善剤、乾癬予防剤又は改善剤、等として用いることができる。 The ceramide production promoter and moisturizer of the present invention can enhance ceramide production in epidermal cells and increase the amount of ceramide in the stratum corneum, thereby enhancing the skin moisturizing function and barrier function. Due to this action, the ceramide production promoter and moisturizer of the present invention can prevent skin diseases caused by a decrease in the amount of ceramide in the stratum corneum, such as dry skin, rough skin, atopic dermatitis, senile psoriasis and psoriasis. Can prevent, mitigate, improve. From this viewpoint, the ceramide production promoter and moisturizer of the present invention are skin barrier function improver, dry skin preventive agent or improver, rough skin preventive agent or improver, atopic dermatitis preventive agent or improver, senile It can be used as an agent for preventing or improving psoriasis, an agent for preventing or improving psoriasis, and the like.
上述した実施形態に関し、本発明はさらに以下の剤、方法、用途及び抽出物を開示する。
＜１＞ シベリアトウヒ（Picea obovata）の抽出物を有効成分として含有する、セラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
＜２＞ 前記抽出物が、シベリアトウヒ（Picea obovata）の葉抽出物である、＜１＞項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
＜３＞ 前記抽出物の含有量が固形分換算で０．００００１質量％以上（好ましくは０．０００１質量％以上）２０質量％以下（好ましくは１０質量％以下）である、＜１＞又は＜２＞項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
The present invention further discloses the following agents, methods, uses and extracts with respect to the above-described embodiments.
<1> Ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic skin, containing an extract of Picea obovata as an active ingredient A preventive / ameliorating agent for inflammation, a preventive / ameliorating agent for senile xerosis, or a prophylactic / ameliorating agent for psoriasis
<2> The ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent according to <1>, wherein the extract is a leaf extract of Picea obovata Rough skin prevention / amelioration agent, atopic dermatitis prevention / amelioration agent, senile xeroderma prevention / amelioration agent, or psoriasis prevention / amelioration agent.
<3> The content of the extract is 0.00001% by mass or more (preferably 0.0001% by mass or more) 20% by mass or less (preferably 10% by mass or less) in terms of solid content, or <1> or <2> ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent, senile xerosis prevention / An improving agent, or a psoriasis preventing / ameliorating agent.
＜４＞ 前記抽出物が、シベリアトウヒ（Picea obovata）を水、アルコール、及び当該アルコールの水溶液から選択される少なくとも１種の溶剤で抽出して得られる抽出物である、＜１＞〜＜３＞のいずれか１項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
＜５＞ 前記溶剤が、水、エタノール水溶液、プロピレングリコール、及びブチレングリコールから選ばれる少なくとも１種である、＜４＞項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
＜６＞ 前記溶剤がエタノール水溶液である、＜４＞又は＜５＞項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
＜７＞ 前記アルコール水溶液の濃度が、５容量％以上（好ましくは３０容量％以上、より好ましくは４０容量％以上）９９容量％以下である、＜４＞〜＜６＞のいずれか１項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
＜８＞ 前記エタノール水溶液の濃度が３０容量％以上であって、４０容量％以上が好ましく、５０容量％以上がさらに好ましく、９９容量％以下であって、９５容量％以下が好ましい、＜６＞項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
＜９＞ 前記抽出物が、前記溶剤をシベリアトウヒ（Picea obovata）１質量部に対して１質量部以上、５０質量部以下用い、３℃以上（好ましくは２０℃以上）、１００℃以下（好ましくは８０℃以下）で、１時間以上（好ましくは１日以上）、数週間以下（好ましくは３０日以下）浸漬又は加熱還流して抽出して得られる抽出物である、＜４＞〜＜８＞のいずれか１項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
＜１０＞ 皮膚外用に供される、＜１＞〜＜９＞のいずれか１項に記載のセラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤。
<4> The extract is an extract obtained by extracting Siberian spruce ( Picea obovata ) with at least one solvent selected from water, alcohol, and an aqueous solution of the alcohol, <1> to <3 > The ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent, senile dry skin Disease prevention / amelioration agent or psoriasis prevention / amelioration agent.
<5> The ceramide production promoter, humectant, skin barrier ability improver, and drying according to <4>, wherein the solvent is at least one selected from water, an aqueous ethanol solution, propylene glycol, and butylene glycol. Skin prevention / amelioration agent, rough skin prevention / improvement agent, atopic dermatitis prevention / amelioration agent, senile xerosis prevention / amelioration agent, or psoriasis prevention / amelioration agent.
<6> The ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent according to <4> or <5>, wherein the solvent is an aqueous ethanol solution. Atopic dermatitis prevention / amelioration agent, senile xerosis prevention / amelioration agent, or psoriasis prevention / amelioration agent.
<7> The concentration of the aqueous alcohol solution is 5% by volume or more (preferably 30% by volume or more, more preferably 40% by volume or more) and 99% by volume or less, according to any one of <4> to <6> The described ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent, senile xerosis prevention / improving agent, or Psoriasis preventive / ameliorating agent.
<8> The concentration of the aqueous ethanol solution is 30% by volume or more, preferably 40% by volume or more, more preferably 50% by volume or more, 99% by volume or less, and preferably 95% by volume or less. <6> Ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent, senile xeroderma prevention / improving agent Or a psoriasis preventive / ameliorating agent.
<9> wherein the extract, the solvent Siberian spruce (Picea obovata) 1 part by mass or more with respect to 1 part by mass, using 50 parts by mass or less, 3 ° C. or higher (more preferably 20 ° C.), 100 ° C. or less (preferably Is an extract obtained by immersing or heating under reflux for 1 hour or more (preferably 1 day or more) and several weeks or less (preferably 30 days or less), <4> to <8 > The ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent, senile dry skin Disease prevention / amelioration agent or psoriasis prevention / amelioration agent.
<10> The ceramide production promoter according to any one of <1> to <9>, provided for external use on the skin, a moisturizer, a skin barrier ability improver, a dry skin prevention / improving agent, a rough skin prevention / An improving agent, an atopic dermatitis preventing / ameliorating agent, a senile xerosis prevention / ameliorating agent, or a psoriasis preventing / ameliorating agent.
＜１１＞ シベリアトウヒ（Picea obovata）の抽出物を含む化粧料を皮膚に適用する、セラミド産生促進方法、保湿方法、皮膚のバリア能向上方法、乾燥肌の予防・改善方法、荒れ肌の予防・改善方法、アトピー性皮膚炎の予防・改善方法、老人性乾皮症の予防・改善方法、又は乾癬の予防・改善方法。（医療行為を除く）。
＜１２＞ シベリアトウヒ（Picea obovata）の抽出物を含む飲食物を経口的に摂取させる、セラミド産生促進方法、保湿方法、皮膚のバリア能向上方法、乾燥肌の予防・改善方法、荒れ肌の予防・改善方法、アトピー性皮膚炎の予防・改善方法、老人性乾皮症の予防・改善方法、又は乾癬の予防・改善方法。（医療行為を除く）。
<11> Applying cosmetics containing an extract of Picea obovata to the skin, ceramide production promotion method, moisturizing method, skin barrier ability improving method, dry skin prevention / improvement method, rough skin prevention / improvement Method, method for preventing / ameliorating atopic dermatitis, method for preventing / ameliorating senile xeroderma, or method for preventing / ameliorating psoriasis. (Excluding medical practice).
<12> Oral intake of food and drink containing an extract of Siberian spruce ( Picea obovata ), ceramide production promotion method, moisturizing method, skin barrier ability improving method, dry skin prevention / improvement method, rough skin prevention / Improvement method, prevention / improvement method of atopic dermatitis, prevention / improvement method of senile xeroderma, or prevention / improvement method of psoriasis. (Excluding medical practice).
＜１３＞ シベリアトウヒ（Picea obovata）の抽出物を、セラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤として使用する方法。
＜１４＞ セラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤としての、シベリアトウヒ（Picea obovata）の抽出物の使用。
＜１５＞ セラミド産生促進、保湿、皮膚のバリア能向上、乾燥肌の予防・改善、荒れ肌の予防・改善、アトピー性皮膚炎の予防・改善、老人性乾皮症の予防・改善、又は乾癬の予防・改善のための、シベリアトウヒ（Picea obovata）の抽出物の非医薬的（非治療的）な使用。
＜１６＞ セラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤の製造のための、シベリアトウヒ（Picea obovata）の抽出物の使用。
＜１７＞ セラミド産生促進、保湿、皮膚のバリア能向上、乾燥肌の予防・改善、荒れ肌の予防・改善、アトピー性皮膚炎の予防・改善、老人性乾皮症の予防・改善、又は乾癬の予防・改善のために用いる、シベリアトウヒ（Picea obovata）の抽出物。
＜１８＞ シベリアトウヒ（Picea obovata）の抽出物を、投与又は皮膚に適用することを含む、セラミド産生促進方法、保湿方法、皮膚のバリア能向上方法、乾燥肌の予防・改善方法、荒れ肌の予防・改善方法、アトピー性皮膚炎の予防・改善方法、老人性乾皮症の予防・改善方法、又は乾癬の予防・改善方法。
<13> An extract of Siberian spruce ( Picea obovata ), ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent , A method of using as a preventive / ameliorating agent for senile xerosis, or a preventive / ameliorating agent for psoriasis.
<14> Ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent, senile xeroderma prevention / improving agent, Alternatively, use of an extract of Siberian spruce ( Picea obovata ) as an agent for preventing / ameliorating psoriasis.
<15> Promotion of ceramide production, moisturization, improvement of skin barrier ability, prevention and improvement of dry skin, prevention and improvement of rough skin, prevention and improvement of atopic dermatitis, prevention and improvement of senile xerosis, or psoriasis Non-medical (non-therapeutic) use of an extract of Siberian spruce ( Picea obovata ) for prevention and improvement.
<16> Ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent, senile xerosis prevention / improving agent, Or use of the extract of Siberian spruce ( Picea obovata ) for the manufacture of an agent for preventing / ameliorating psoriasis.
<17> Promotion of ceramide production, moisturization, improvement of skin barrier ability, prevention / improvement of dry skin, prevention / improvement of rough skin, prevention / improvement of atopic dermatitis, prevention / improvement of senile xerosis, or psoriasis An extract of Picea obovata used for prevention and improvement.
<18> Ceramide production promotion method, moisturizing method, skin barrier ability improving method, dry skin prevention / improvement method, rough skin prevention, including administration or application to the skin of an extract of Picea obovata -Improvement method, prevention / improvement method of atopic dermatitis, prevention / improvement method of senile xeroderma, or prevention / improvement method of psoriasis.
＜１９＞ 前記抽出物が、シベリアトウヒ（Picea obovata）の葉抽出物である、＜１１＞〜＜１８＞のいずれか１項に記載の抽出物、方法又は使用。
＜２０＞ 前記セラミド産生促進剤、保湿剤、皮膚のバリア能向上剤、乾燥肌予防・改善剤、荒れ肌予防・改善剤、アトピー性皮膚炎予防・改善剤、老人性乾皮症予防・改善剤、又は乾癬予防・改善剤中の、シベリアトウヒ（Picea obovata）抽出物の含有量が固形分換算で０．００００１質量％以上（好ましくは０．０００１質量％以上）２０質量％以下（好ましくは１０質量％以下）である、前記＜１３＞、＜１４＞及び＜１６＞のいずれか１項記載の方法又は使用。
＜２１＞ 前記抽出物が、前記植物を水、アルコール、及び当該アルコールの水溶液から選択される少なくとも１種の溶剤で抽出して得られる抽出物である、＜１１＞〜＜２０＞のいずれか１項に記載の抽出物、方法又は使用。
＜２２＞ 前記溶剤が、水、エタノール水溶液、プロピレングリコール、及びブチレングリコールから選ばれる少なくとも１種である、＜２１＞項に記載の抽出物、方法又は使用。
＜２３＞ 前記溶剤がエタノール水溶液である、＜２１＞又は＜２２＞項に記載の抽出物、方法又は使用。
＜２４＞ 前記アルコール水溶液の濃度が、５容量％以上（好ましくは３０容量％以上、より好ましくは４０容量％以上）９９容量％以下である、＜２１＞〜＜２３＞のいずれか１項に記載の抽出物、方法又は使用。
＜２５＞ 前記エタノール水溶液の濃度が３０容量％以上であって、４０容量％以上が好ましく、５０容量％以上がさらに好ましく、９９容量％以下であって、９５容量％以下が好ましい、＜２３＞項に記載の抽出物、方法又は使用。
＜２６＞ 前記抽出物が、前記溶剤を植物１質量部に対して１質量部以上、５０質量部以下用い、３℃以上（好ましくは２０℃以上）、１００℃以下（好ましくは８０℃以下）で、１時間以上（好ましくは１日以上）、数週間以下（好ましくは３０日以下）浸漬又は加熱還流して抽出して得られる抽出物である、＜２１＞〜＜２５＞のいずれか１項に記載の抽出物、方法又は使用。
＜２７＞ 皮膚外用に供される、＜１１＞〜＜２６＞のいずれか１項に記載の抽出物、方法又は使用。
<19> The extract, method or use according to any one of <11> to <18>, wherein the extract is a leaf extract of Picea obovata .
<20> Ceramide production promoter, moisturizer, skin barrier ability improver, dry skin prevention / improving agent, rough skin prevention / improving agent, atopic dermatitis prevention / improving agent, senile xerosis prevention / improving agent The content of the extract of Picea obovata in the agent for preventing / ameliorating psoriasis is 0.00001% by mass or more (preferably 0.0001% by mass or more) in terms of solid content and 20% by mass or less (preferably 10 The method or use according to any one of the above <13>, <14>, and <16>, which is not more than mass%.
<21> The extract according to any one of <11> to <20>, wherein the extract is an extract obtained by extracting the plant with at least one solvent selected from water, alcohol, and an aqueous solution of the alcohol. 2. Extract, method or use according to 1.
<22> The extract, method or use according to <21>, wherein the solvent is at least one selected from water, an aqueous ethanol solution, propylene glycol, and butylene glycol.
<23> The extract, method or use according to <21> or <22>, wherein the solvent is an aqueous ethanol solution.
<24> The concentration of the aqueous alcohol solution is 5% by volume or more (preferably 30% by volume or more, more preferably 40% by volume or more) and 99% by volume or less, according to any one of <21> to <23> The described extract, method or use.
<25> The concentration of the aqueous ethanol solution is 30% by volume or more, preferably 40% by volume or more, more preferably 50% by volume or more, 99% by volume or less, and preferably 95% by volume or less, <23> The extract, method or use according to paragraph.
<26> The extract uses the solvent in an amount of 1 part by mass or more and 50 parts by mass or less based on 1 part by mass of the plant. Any one of <21> to <25>, which is an extract obtained by immersion or heating under reflux for 1 hour or more (preferably 1 day or more) and several weeks or less (preferably 30 days or less). The extract, method or use according to paragraph.
<27> The extract, method or use according to any one of <11> to <26>, which is provided for external use on the skin.
以下、本発明を実施例に基づきさらに詳細に説明するが、本発明はこれに限定されるものではない。 EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to this.
（製造例１）シベリアトウヒ５０％エタノール抽出物の調製
モンゴル産のシベリアトウヒの葉１４ｇを細切し、５０％エタノール１４０ｍＬを加え、室温で１７日間抽出を行った。その後、濾過して、シベリアトウヒ５０％エタノール抽出物１１０ｍＬを得た。得られた抽出物について、下記の方法で蒸発残分を算出したところ、蒸発残分は１．３９％（ｗ／ｖ）であった。これを５０％エタノール水溶液で希釈して、１．０％（ｗ／ｖ）（エキス固形分）抽出物を調製した。
(Production Example 1) Preparation of Siberian Spruce 50% Ethanol Extract 14 g of Siberian Spruce leaves from Mongolia were chopped, 140 mL of 50% ethanol was added, and extraction was performed at room temperature for 17 days. Then, it filtered and 110 mL of Siberian spruce 50% ethanol extract was obtained. About the obtained extract, when the evaporation residue was computed with the following method, the evaporation residue was 1.39% (w / v). This was diluted with 50% aqueous ethanol solution to prepare 1.0% (w / v) (extract solid content) extract.
＜蒸発残分の算出＞
シベリアトウヒ抽出物１ｍｌを１０５℃で６時間乾燥させたところ（乾燥機：ＤＲＹ Ｔｈｅｒｍｏ Ｕｎｉｔ ＤＴＵ−１Ｃ（ＴＡＩＴＥＣ ＣＯＲＰＯＲＡＴＩＯＮ社製）使用）、乾燥物１３．９ｍｇが得られた。この抽出物の蒸発残分を、１３．９÷１０００×１００＝１．３９％（ｗ／ｖ）と算出した。なお、下記においても、植物抽出物の蒸発残分は同様にして算出されたものである。
<Calculation of evaporation residue>
When 1 ml of the Siberian spruce extract was dried at 105 ° C. for 6 hours (using a dryer: DRY Thermo Unit DTU-1C (manufactured by TAITEC CORPORATION)), 13.9 mg of a dried product was obtained. The evaporation residue of this extract was calculated as 13.9 ÷ 1000 × 100 = 1.39% (w / v). In the following, the evaporation residue of the plant extract is calculated in the same manner.
（試験例）セラミド産生促進効果の検証
培養プレートを用い、培養液（商品名：EpiLife-KG2、KURABO社製）中にて、正常ヒト表皮角化細胞（商品名：NHEK(F)、KURABO社製）を３７℃、５％ＣＯ2で培養した。
その後、培養液を上皮成長因子などの増殖因子を除いたEpiLife-KG2に換え、上記製造例で調製した濃度１．０ｗ／ｖ％（固形分換算）の抽出物、又はコントロール溶液として５０％エタノールを、０．１％量添加した（抽出物の終濃度：０．００１（ｗ／ｖ）％）。
３日間培養した後、各々の細胞を１ｗｅｌｌごと回収した。
(Test example) Verification of ceramide production promoting effect Normal human epidermal keratinocytes (trade name: NHEK (F), KURABO) in culture solution (trade name: EpiLife-KG2, manufactured by KURABO) using a culture plate Manufactured at 37 ° C. and 5% CO 2 .
Thereafter, the culture solution was replaced with EpiLife-KG2 from which growth factors such as epidermal growth factor were removed, and an extract with a concentration of 1.0 w / v% (in terms of solid content) prepared in the above production example, or 50% ethanol as a control solution. Was added in an amount of 0.1% (final concentration of the extract: 0.001 (w / v)%).
After culturing for 3 days, each cell was collected together with 1 well.
回収した細胞からBligh and Dyer法により脂質を抽出した有機相をガラス管に移し、窒素乾固した後、クロロホルム、メタノールで再溶解し、脂質サンプルとした。
また、脂質を抽出した後の細胞に０．１Ｎ ＮａＯＨ、１％ＳＤＳ水溶液を加え、６０℃で２時間加熱することにより、タンパク質を可溶化し、室温まで冷却した後２Ｎ ＨＣｌを加えて中和し、タンパク量をＢＣＡ法により定量した。
The organic phase from which the lipid was extracted from the collected cells by the Bligh and Dyer method was transferred to a glass tube, solidified with nitrogen, and then redissolved with chloroform and methanol to obtain a lipid sample.
In addition, 0.1N NaOH, 1% SDS aqueous solution is added to the cells after lipid extraction, and the protein is solubilized by heating at 60 ° C. for 2 hours, cooled to room temperature, and then neutralized by adding 2N HCl. The amount of protein was quantified by the BCA method.
調製した脂質サンプルを薄膜クロマトグラフィー（ＴＬＣ）でクロロホルム：メタノール：酢酸＝１９０：９：１で２回水平展開した。硫酸銅液をスプレーで噴霧し、ホットプレートで焼き付けセラミドを検出し、セラミド量とした。
結果を表１に示す。なお、表１のセラミド量は、コントロール溶液を添加した系のセラミド量を１とした場合の相対値（ｎ＝３の平均値）を示している。
The prepared lipid sample was horizontally developed by thin film chromatography (TLC) twice with chloroform: methanol: acetic acid = 190: 9: 1. The copper sulfate solution was sprayed and sprayed with a hot plate to detect ceramide, and the amount was determined.
The results are shown in Table 1. In addition, the amount of ceramide in Table 1 shows a relative value (average value of n = 3) when the amount of ceramide in the system to which the control solution is added is 1.
（参考例）
１．ユーカリ抽出物の調製
ユーカリノキ（Eucalyptus globulus Labillardiere：新和物産株式会社より購入）の葉４０ｇを細切し、５０％エタノール４００ｍＬを加え、室温・静置条件下で７日間抽出を行った。その後、濾過して、ユーカリ抽出物２９１ｍＬを得た。得られた抽出物について、上記の方法で蒸発残分を算出したところ、蒸発残分は３．１６％（ｗ／ｖ）であった。
(Reference example)
1. Preparation of Eucalyptus Extract 40 g of Eucalyptus globulus Labillardiere (purchased from Shinwa Bussan Co., Ltd.) was cut into small pieces, added with 400 mL of 50% ethanol, and extracted for 7 days at room temperature and standing conditions. Then, it filtered and 291 mL of eucalyptus extracts were obtained. When the evaporation residue was calculated by the above method for the obtained extract, the evaporation residue was 3.16% (w / v).
２．セラミド産生促進効果の検証
得られたユーカリ抽出物を用いて、上記試験例と同様の手法によってセラミド産生促進効果を検証した。なお、細胞への添加は、濃度が固形分換算で１％（ｗ／ｖ）となるように調整した抽出物を、０．００１％添加した。
結果を表１に示す。なお、ユーカリ抽出物は前記のとおり、セラミド産生促進作用を有する保湿成分として公知のものである。
2. Verification of ceramide production promoting effect Using the obtained eucalyptus extract, the ceramide production promoting effect was verified by the same method as in the above test example. In addition, 0.001% of the extract adjusted so that a density | concentration might be 1% (w / v) in conversion of solid content added to the cell.
The results are shown in Table 1. The eucalyptus extract is known as a moisturizing component having a ceramide production promoting action as described above.
表１から明らかなように、シベリアトウヒの抽出物を添加した系では、コントロールの系に比べてセラミド量が増加した。すなわち、シベリアトウヒ抽出物は優れたセラミド産生促進作用を有し、セラミド産生促進剤として有用であることがわかった。さらに、シベリアトウヒ抽出物は、公知の保湿成分であるユーカリ抽出物と同等のセラミド産生作用を有することから、保湿剤として有用であることがわかった。 As is clear from Table 1, the amount of ceramide increased in the system to which the extract of Siberian spruce was added as compared with the control system. That is, it was found that the Siberian spruce extract has an excellent ceramide production promoting action and is useful as a ceramide production promoter. Further, the Siberian spruce extract has a ceramide producing action equivalent to that of the eucalyptus extract, which is a known moisturizing component, and thus was found to be useful as a moisturizing agent.
（処方例）
前記製造例で得られた抽出物を有効成分として、下記に示す組成の化粧水、0/W（オイルインウォーター）型乳液、W/O（ウォーターインオイル）型クリーム、ジェル状化粧料、液体入浴剤を常法により各々製造できる。
(Prescription example)
Using the extract obtained in the above production example as an active ingredient, lotion having the following composition, 0 / W (oil-in-water) type emulsion, W / O (water-in-oil) type cream, gel cosmetic, liquid Bathing agents can be produced by conventional methods.
化粧水の調製
（組成） （配合：質量％）
シベリアトウヒ抽出物 ３．００
ポリエチレングリコール（商品名：ＰＥＧ−１５４０、三洋化成社製） １．００
ポリオキシエチレン（２０）ソルビタンモノラウリン酸エステル １．５０
グリセリン ２．００
パラべン ０．１０
精製水 残余
Preparation of lotion (composition) (formulation: mass%)
Siberian spruce extract 3.00
Polyethylene glycol (trade name: PEG-1540, manufactured by Sanyo Chemical Industries) 1.00
Polyoxyethylene (20) sorbitan monolaurate 1.50
Glycerin 2.00
Paraben 0.10
Purified water residue
０／Ｗ型乳液の調製
（組成） （配合：質量％）
シベリアトウヒ抽出物 ３．００
ポリエチレングリコール（商品名：ＰＥＧ−２０００、三洋化成社製） １．００
プルラン（商品名：プルランＰＴ−２０、林原社製） ０．４０
セチルアルコール １．００
ワセリン ２．００
スクワラン ６．００
ジメチルポリシロキサン ２．００
グリセリン ２．００
擬似セラミド（Ｎ−（３−ヘキサデシロキシ−２−ヒドロキシプロピル）−Ｎ−２−ヒドロキシエチルヘキサデカミナド） １．００
ポリオキシエチレン（１０）モノオレイン酸エステル １．００
グリセロールモノステアリン酸エステル １．００
植物のカルス由来の酸性へテロ多糖類（チュベロース多糖１重量％水溶液）２．００
パラべン ０．２０
精製水 残余
Preparation (composition) of 0 / W type emulsion (formulation: mass%)
Siberian spruce extract 3.00
Polyethylene glycol (trade name: PEG-2000, manufactured by Sanyo Chemical Co., Ltd.) 1.00
Pullulan (trade name: Pullulan PT-20, manufactured by Hayashibara) 0.40
Cetyl alcohol 1.00
Vaseline 2.00
Squalane 6.00
Dimethylpolysiloxane 2.00
Glycerin 2.00
Pseudoceramide (N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethylhexadecaminad) 1.00
Polyoxyethylene (10) monooleate 1.00
Glycerol monostearate 1.00
Acid heteropolysaccharide derived from plant callus (1% by weight aqueous solution of tuberose polysaccharide) 2.00
Paraben 0.20
Purified water residue
Ｗ／Ｏ型クリームの調製
（組成） （配合：質量％）
シベリアトウヒ抽出物 ３．００
アクリル酸アルキル共重合体（商品名：ヨドゾールＧＨ８１０、カネボウＮＳＣ社製）
１．３０
ポリビニルピロリドン（商品名：ルビスコールＫ−９０、ＢＡＳＥジャパン社製）
０．７０
ジメチルポリシロキサン １０．００
メチルフェニルポリシロキサン ３．００
オクタメチルシクロテトラシロキサン １２．００
ポリオキシアルキレン変性シリコーン ５．００
１，３−ブチレングリコール ６．００
擬似セラミド（Ｎ−（３−ヘキサデシロキシ−２−ヒドロキシプロピル）−Ｎ−２−ヒドロキシエチルヘキサデカミナド） １．２０
パラべン ０．２０
香料 微量
精製水 残余
Preparation (composition) of W / O type cream (formulation: mass%)
Siberian spruce extract 3.00
Alkyl acrylate copolymer (trade name: Yodosol GH810, manufactured by Kanebo NSC)
1.30
Polyvinylpyrrolidone (Brand name: Rubiscol K-90, manufactured by BASE Japan)
0.70
Dimethylpolysiloxane 10.00
Methylphenylpolysiloxane 3.00
Octamethylcyclotetrasiloxane 12.00
Polyoxyalkylene-modified silicone 5.00
1,3-butylene glycol 6.00
Pseudoceramide (N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethylhexadecaminad) 1.20
Paraben 0.20
Perfume Trace amount purified water Residual
ジェル状化粧料の調製
（組成） （配合：質量％）
シベリアトウヒ抽出物 １．００
ポリエチレングリコール（商品名：ＰＥＧ−２０００、三洋化成社製） ０．５０
キサンタンガム（商品名：ネオソフトＸＫＫ、興人社製） ０．２０
グリセリン ３．００
エタノール ３．００
カルボキシビニルポリマー ０．５０
水酸化カリウム ０．１５
ポリオキシエチレン硬化ヒマシ油 １．００
クエン酸 ０．８０
クエン酸三ナトリウム ０．８０
ナイロンパウダー １．００
パラべン ０．１０
香料 微量
精製水 残余
Preparation (composition) of gel cosmetic (formulation: mass%)
Siberian spruce extract 1.00
Polyethylene glycol (trade name: PEG-2000, manufactured by Sanyo Chemical Co., Ltd.) 0.50
Xanthan gum (trade name: Neosoft XKK, manufactured by Kojinsha) 0.20
Glycerin 3.00
Ethanol 3.00
Carboxyvinyl polymer 0.50
Potassium hydroxide 0.15
Polyoxyethylene hydrogenated castor oil 1.00
Citric acid 0.80
Trisodium citrate 0.80
Nylon powder 1.00
Paraben 0.10
Perfume Trace amount purified water Residual
液体入浴剤の調製
（組成） （配合：質量％）
シベリアトウヒ抽出物 ３．００
擬似セラミド（Ｎ−（３−ヘキサデシロキシ−２−ヒドロキシプロピル）−Ｎ−２−ヒドロキシエチルヘキサデカミナド） ０．１０
ミリスチン酸イソプロピル １５．００
ポリオキシエチレン（１２）オレイルエーテル １０．００
ポリオキシエチレン（６）オレイルエーテル ６．００
植物のカルス由来の酸性へテロ多糖類（チュベロース多糖１重量％水溶液）２．００
パラべン ０．３０
香料 微量
流動パラフィン 残余
Preparation of liquid bathing agent (composition) (formulation: mass%)
Siberian spruce extract 3.00
Pseudoceramide (N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethylhexadecaminad) 0.10
Isopropyl myristate 15.00
Polyoxyethylene (12) oleyl ether 10.00
Polyoxyethylene (6) oleyl ether 6.00
Acid heteropolysaccharide derived from plant callus (1% by weight aqueous solution of tuberose polysaccharide) 2.00
Paraben 0.30
Perfume Micro liquid paraffin Residue
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