JP6902329B2 - Inhibitor of sebaceous gland cell activation - Google Patents
Inhibitor of sebaceous gland cell activation Download PDFInfo
- Publication number
- JP6902329B2 JP6902329B2 JP2016075502A JP2016075502A JP6902329B2 JP 6902329 B2 JP6902329 B2 JP 6902329B2 JP 2016075502 A JP2016075502 A JP 2016075502A JP 2016075502 A JP2016075502 A JP 2016075502A JP 6902329 B2 JP6902329 B2 JP 6902329B2
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- JP
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- Prior art keywords
- burdock
- acne
- sebaceous gland
- sebaceous
- present
- Prior art date
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Description
本発明は、皮脂腺細胞の活性化の抑制剤、皮脂腺細胞の活性化を抑制するための組成物および皮脂腺細胞の活性化を抑制するための食品組成物に関する。 The present invention relates to an agent for suppressing the activation of sebaceous gland cells, a composition for suppressing the activation of sebaceous gland cells, and a food composition for suppressing the activation of sebaceous gland cells.
皮脂腺（脂腺）は、皮膚の内部に存在し、皮脂を分泌する外分泌腺である。皮脂腺は、皮脂を産生する皮脂腺細胞（脂腺細胞）を有する。皮脂腺細胞は、細胞内に脂肪滴（本明細書において「脂質滴」または「油滴」ともいう。）を形成する。脂肪滴を形成しつつある皮脂腺細胞や脂肪滴が充満した細胞は分化細胞とよばれ、分化細胞が崩壊することにより皮脂が分泌される。 Sebaceous glands (sebaceous glands) are exocrine glands that exist inside the skin and secrete sebum. Sebaceous glands have sebaceous gland cells (sebaceous gland cells) that produce sebum. Sebaceous gland cells form intracellular lipid droplets (also referred to herein as "lipid droplets" or "oil droplets"). Sebaceous gland cells forming lipid droplets and cells filled with lipid droplets are called differentiated cells, and sebum is secreted when the differentiated cells collapse.
皮脂は、脂肪腺から分泌される脂肪などを含む液体である。皮脂は、皮脂腺細胞が脂肪滴を蓄積した後崩壊することによって皮脂腺内腔に放出され、その後皮膚表面に分泌される。ヒトの皮脂の主要成分は、ワックスエステル、トリグリセリドおよびスクアレンであり、これらは、純粋に皮脂腺細胞から産生される。一方、分泌される皮脂にはコレステロールエステルやコレステロールが含まれるが、これらは皮脂腺細胞膜の崩壊産物や表皮に由来する。また、分泌される皮脂には遊離脂肪酸も含まれるが、これは分泌後にトリグリセリドが加水分解して生じるといわれている。 Sebum is a liquid containing fat and the like secreted from the fat glands. Sebum is released into the sebaceous gland lumen by the sebaceous gland cells accumulating lipid droplets and then collapsing, and then secreted to the skin surface. The main components of human sebum are wax esters, triglycerides and squalene, which are produced purely from sebaceous gland cells. On the other hand, the secreted sebum contains cholesterol ester and cholesterol, which are derived from the disrupted products of the sebaceous gland cell membrane and the epidermis. The secreted sebum also contains free fatty acids, which are said to be produced by the hydrolysis of triglycerides after secretion.
皮脂腺には、ホルモン、レチノイド、遊離脂肪酸および外来性物質などの多数の因子が影響を及ぼしている。皮脂腺に影響を及ぼすホルモンには、アンドロゲン、エストロゲン、プロゲステロン、糖質コルチコイド、下垂体ホルモン、甲状腺ホルモンおよびインスリンなどが挙げられる。アンドロゲンは特に重要であり、皮脂腺を発達させ、多くの皮脂を合成および分泌させることが報告されている。一方、エストロゲンは、皮脂腺の活動を抑制することが知られている。このように、皮脂腺に影響を及ぼす因子には、皮脂腺の活動を活発化させるものと抑制させるものがある。 The sebaceous glands are affected by a number of factors, including hormones, retinoids, free fatty acids and foreign substances. Hormones that affect the sebaceous glands include androgens, estrogens, progesterone, glucocorticoids, pituitary hormones, thyroid hormones and insulin. Androgens are of particular importance and have been reported to develop sebaceous glands and synthesize and secrete a large amount of sebum. On the other hand, estrogen is known to suppress the activity of sebaceous glands. Thus, factors that affect the sebaceous glands include those that activate and those that suppress the activity of the sebaceous glands.
また、皮脂腺は、加齢に伴って体積が変化する。皮脂腺は、新生児では大きく、乳児において萎縮するが、思春期にアンドロゲンの影響を受けて増大する。脂腺細胞の体積変化は、性別によっても異なっている。 In addition, the volume of sebaceous glands changes with aging. Sebaceous glands are large in newborns and atrophied in infants, but grow under the influence of androgens during puberty. The volume change of fat gland cells also differs depending on the sex.
皮膚上に分泌された皮脂は、表皮の保湿や、病原菌の侵入からの保護のために働くと言われているが、その機能ははっきりとは分かっていない。皮脂腺は、いくつかの疾患に関与することが報告されている（非特許文献1）。皮脂腺は、たとえばざ瘡、ざ瘡様発疹症、酒さ、劇症酒さ、口囲皮膚炎、酒さ様皮膚炎、顔面播種状粟粒性狼瘡、脂漏、脂漏性皮膚炎、マラセチア毛包炎、皮脂欠乏症、面皰母斑、脂腺母斑、脂腺増殖症、多発性脂腺嚢腫、脂腺腺腫および脂腺癌などに関与することが報告されている。ざ瘡には、尋常性ざ瘡（いわゆるにきび）などが含まれる。 Sebum secreted on the skin is said to work to moisturize the epidermis and protect it from the invasion of pathogens, but its function is not clearly understood. Sebaceous glands have been reported to be involved in several diseases (Non-Patent Document 1). Sebaceous glands include, for example, rosacea, rosacea-like rash, rosacea, fulminant rosacea, mouth circumference dermatitis, rosacea-like dermatitis, facial disseminated rosacea, seborrheic dermatitis, seborrheic dermatitis, and maracetian hair. It has been reported to be involved in seborrheic dermatitis, rosacea deficiency, rosacea, sebaceous gland plaque, sebaceous proliferative disorder, multiple sebaceous cysts, sebaceous adenoma and sebaceous cancer. Acne includes acne vulgaris (so-called acne) and the like.
皮脂腺細胞が関与する様々な疾患に対する新たな治療方法の開発が望まれている。そこで、本発明は、皮脂腺細胞の活性化を抑制することができる新規の抑制剤および組成物を提供することを目的とする。 The development of new therapeutic methods for various diseases involving sebaceous gland cells is desired. Therefore, an object of the present invention is to provide a novel inhibitor and composition capable of suppressing the activation of sebaceous gland cells.
本発明者らは、上記課題を解決するために鋭意検討を行った結果、皮脂腺細胞をアルクチゲニンで処理したときに、皮脂腺細胞における脂質合成量を有意に減少させ、脂肪滴の大きさを有意に減少させることを見出した。これらの結果から、本発明者らは、アルクチゲニンに皮脂腺細胞の活性化を抑制する作用があることを見出し、本発明を完成させた。 As a result of diligent studies to solve the above problems, the present inventors significantly reduced the amount of lipid synthesis in sebaceous gland cells and significantly increased the size of lipid droplets when the sebaceous gland cells were treated with arctigenin. Found to reduce. From these results, the present inventors have found that arctigenin has an action of suppressing the activation of sebaceous gland cells, and completed the present invention.
本発明は、アルクチゲニンおよび／またはアルクチインを有効成分として含有する、皮脂腺細胞の活性化の抑制剤を提供する。 The present invention provides an inhibitor of sebaceous gland cell activation containing arctigenin and / or arctiin as an active ingredient.
また本発明は、アルクチゲニンおよび／またはアルクチインを有効成分として含有する、皮脂腺細胞の活性化を抑制するための組成物を提供する。 The present invention also provides a composition containing arctigenin and / or arctiin as an active ingredient for suppressing the activation of sebaceous gland cells.
また本発明は、アルクチゲニンおよび／またはアルクチインを、ゴボウ、ゴボウシ、ゴボウスプラウトもしくはレンギョウまたはこれらから抽出したエキスとして含有する、上記組成物を提供する。 The present invention also provides the above composition containing arktigenin and / or alktiin as burdock, burdock, burdock sprout or forsythia or an extract extracted from these.
また本発明は、上記組成物を含有する医薬品を提供する。 The present invention also provides a pharmaceutical product containing the above composition.
また本発明は、上記組成物を含有する化粧品を提供する。 The present invention also provides a cosmetic product containing the above composition.
また本発明は、アルクチゲニンおよび／またはアルクチインを有効成分として含有する、皮脂腺細胞の活性化を抑制するための食品組成物を提供する。 The present invention also provides a food composition containing arctigenin and / or arctiin as an active ingredient for suppressing the activation of sebaceous gland cells.
また本発明は、アルクチゲニンおよび／またはアルクチインを、ゴボウ、ゴボウシ、ゴボウスプラウトもしくはレンギョウまたはこれらから抽出したエキスとして含有する、上記食品組成物を提供する。 The present invention also provides the above-mentioned food composition containing arktigenin and / or alktiin as burdock, burdock, burdock sprout or forsythia or an extract extracted from these.
本発明の抑制剤および組成物は、皮脂腺細胞における脂質の合成および蓄積を抑制することができる。したがって、本発明によれば、皮脂腺細胞における脂質の蓄積や、皮脂の分泌の亢進または過剰により生じる様々な疾患や症状を治療、改善および予防するための新たな治療方法を確立することができる。 The inhibitors and compositions of the present invention can suppress the synthesis and accumulation of lipids in sebaceous gland cells. Therefore, according to the present invention, it is possible to establish a new therapeutic method for treating, ameliorating and preventing various diseases and symptoms caused by the accumulation of lipids in sebaceous gland cells and the increased or excessive secretion of sebum.
本発明は、皮脂腺細胞の活性化を抑制するための抑制剤を提供する。 The present invention provides an inhibitor for suppressing the activation of sebaceous gland cells.
本明細書において「皮脂腺細胞」は、皮脂腺に含まれ、皮脂を産生する細胞（脂腺細胞）をいう。また、本明細書において「皮脂腺細胞の活性化」とは、皮脂腺細胞が脂質を合成または蓄積すること、あるいは皮脂腺細胞が細胞内に脂肪滴を形成することをいう。本明細書において「皮脂腺細胞の活性化を抑制する」とは、皮脂腺細胞における脂質の合成または蓄積を抑制すること、皮脂腺細胞内の脂質の合成量または蓄積量を減少させること、あるいは皮脂腺細胞における脂肪滴形成を抑制することを意味する。皮脂腺細胞において合成または蓄積される脂質には、たとえばグリセリン脂肪酸エステル、トリグリセリド、ワックスエステルおよびスクアレンなどが含まれる。 In the present specification, "sebaceous gland cell" refers to a cell (sebaceous gland cell) contained in the sebaceous gland and producing sebum. Further, in the present specification, "activation of sebaceous gland cells" means that sebaceous gland cells synthesize or accumulate lipids, or that sebaceous gland cells form lipid droplets in the cells. As used herein, "suppressing the activation of sebaceous gland cells" means suppressing the synthesis or accumulation of lipids in sebaceous gland cells, reducing the amount of lipid synthesis or accumulation in sebaceous gland cells, or in sebaceous gland cells. It means suppressing the formation of lipid droplets. Lipids synthesized or accumulated in sebaceous gland cells include, for example, glycerin fatty acid esters, triglycerides, wax esters and squalene.
本発明の抑制剤は、アルクチゲニンおよび／またはアルクチインを有効成分として含有する。アルクチゲニンおよびアルクチインは、ゴボウ等の植物に含まれるジフェニルプロパノイド（リグナン類）の1つである。アルクチインは、アルクチゲニンの前駆体であり、生体内で代謝されてアルクチゲニンになることが知られている。アルクチゲニンおよび／またはアルクチインとして、化学的に合成したアルクチゲニンおよび／またはアルクチインを用いてもよいし、植物から単離したアルクチゲニンおよび／またはアルクチインを用いてもよい。また、アルクチゲニンおよび／またはアルクチインとして、アルクチゲニンおよび／またはアルクチインを含む植物そのものまたは植物から抽出したエキスを用いてもよい。アルクチゲニンおよび／またはアルクチインを含む植物には、たとえばゴボウ（スプラウト・葉・根茎・ゴボウシ）、アイノコレンギョウ（花・葉・果実・根茎）、チョウセンレンギョウ（花・葉・果実・根茎）、レンギョウ（花・葉・果実・根茎）、シナレンギョウ（花・葉・果実・根茎）、ベニバナ、ヤグルマギク、アメリカオニアザミ、サントリソウ（ギバナアザミ）、カルドン、ゴロツキアザミ、アニウロコアザミ、ゴマ、モミジヒルガオ、シンチクヒメハギ、チョウセンテイカカズラ、テイカカズラ、ムニンテイカカズラ、ヒメテイカカズラ、トウキョウチクトウ、ケテイカカズラ、リョウカオウ、オオケタデ、ヤマザクラ、シロイヌナズナ、アマランス、クルミ、エンバク、スペルタコムギ、軟質コムギ、メキシコイトスギおよびカヤが含まれる。なかでも、ゴボウ（特にゴボウシおよびゴボウスプラウト）およびレンギョウ（特に葉）は、アルクチゲニンおよび／またはアルクチインの含有量が高いため好ましい。 The inhibitor of the present invention contains arctigenin and / or arctiin as an active ingredient. Arctigenin and arctiin are one of the diphenylpropanoids (lignans) contained in plants such as burdock. Arctiin is a precursor of arctigenin and is known to be metabolized in vivo to become arctigenin. As the arctigenin and / or arctiin, chemically synthesized arctigenin and / or arctiin may be used, or plant-isolated arctigenin and / or arctiin may be used. Further, as alktigenin and / or alktiin, the plant itself containing alktigenin and / or arktiin or an extract extracted from the plant may be used. Plants containing Asiatic jasmine and / or Asiatic jasmine include, for example, forsythia (sprouts, leaves, rhizomes, forsythia), forsythia jasmine (flowers, leaves, fruits, rhizomes), forsythia forsythia (flowers, leaves, fruits, rhizomes), forsythia (flowers).・ Leaves / Fruits / Rhizome), Forsythia (Flowers / Leaves / Fruits / Rhizome), Benibana, Yagurumagiku, Americatic jasmine, Santorisou (Gibana thistle), Cardon, Gorotsuki thistle, Aniuro koazami, Sesame, Momiji hirugao, Shinchikuhimehagi, Asiatic jasmine, Asiatic jasmine, Asiatic jasmine, Asiatic jasmine, Asiatic jasmine, Asiatic jasmine, Forsythia, Forsythia, Asiatic jasmine, Yamazakura, Forsythia, Amaranth, walnut, Enbaku, Spell tacomi, soft wheat, Mexican sardine. Of these, burdock (particularly burdock and burdock sprout) and forsythia (particularly leaves) are preferred because of their high content of alktigenin and / or alktiin.
アルクチゲニンおよび／またはアルクチインとして植物から抽出したエキスを用いる場合、エキスは、たとえば以下の方法によって植物から調製してもよい。本発明において使用されるエキスは、たとえばアルクチゲニンおよび／またはアルクチインを含む植物から、酵素変換工程および有機溶媒による抽出工程の2段階により抽出してもよい。 When using an extract extracted from a plant as arctigenin and / or arctiin, the extract may be prepared from the plant by, for example, the following method. The extract used in the present invention may be extracted from a plant containing, for example, arctigenin and / or arctiin by two steps, an enzyme conversion step and an extraction step with an organic solvent.
酵素変換工程は、植物に内在する酵素であるβ-グルコシダーゼにより、該植物に含まれているアルクチインをアルクチゲニンに酵素変換する工程である。具体的には、植物を乾燥し切栽したものを適切な温度に保持することにより内在のβ-グルコシダーゼを作用させて、アルクチインからアルクチゲニンへの反応を進行させる。たとえば、切裁した植物に水などの任意の溶液を加えて、30℃付近の温度（20〜50℃）の間にて攪拌することなどにより、植物を任意の温度に保持することができる。 The enzyme conversion step is a step of enzymatically converting arctiin contained in the plant into arctigenin by β-glucosidase, which is an enzyme inherent in the plant. Specifically, by keeping a dried and cut plant at an appropriate temperature, the endogenous β-glucosidase acts to promote the reaction from arctiine to alktigenin. For example, the plant can be kept at an arbitrary temperature by adding an arbitrary solution such as water to the cut plant and stirring the mixture at a temperature of around 30 ° C. (20 to 50 ° C.).
有機溶媒による抽出工程は、任意の適切な有機溶媒を使用して、植物からアルクチゲニンおよびアルクチインを抽出する工程である。すなわち、上記の酵素変換工程によりアルクチゲニンが高含量となった状態で、適切な溶媒を添加して、植物からエキスを抽出する工程である。たとえば、植物に適切な溶媒を添加して、適切な時間加熱攪拌してエキスを抽出する。また、加熱攪拌以外にも、加熱還流、ドリップ式抽出、浸漬式抽出または加圧式抽出法などの当業者に公知の任意の抽出法を使用して、エキスを抽出することができる。 The extraction step with an organic solvent is a step of extracting arctigenin and arctiin from a plant using any suitable organic solvent. That is, it is a step of extracting an extract from a plant by adding an appropriate solvent in a state where the content of arctigenin is high by the above-mentioned enzyme conversion step. For example, the appropriate solvent is added to the plant and the extract is extracted by heating and stirring for an appropriate period of time. In addition to heating and stirring, the extract can be extracted using any extraction method known to those skilled in the art, such as heating reflux, drip extraction, immersion extraction, or pressure extraction.
アルクチゲニンは水難溶性であることから、有機溶媒を添加することにより、アルクチゲニンの収率を向上させることができる。有機溶媒は、任意の有機溶媒を使用することができる。たとえば、メタノール、エタノールおよびプロパノールなどのアルコール、並びにアセトンを使用することができる。安全性の面を考慮すると、本発明の皮脂腺細胞活性化抑制剤に用いるエキスの製造方法では、有機溶媒として30％量のエタノールを使用することが好ましい。エキスから溶媒を留去するとペースト状の濃縮物が得られ、この濃縮物をさらに乾燥すると乾燥物を得ることができる。 Since arctigenin is poorly soluble in water, the yield of arctigenin can be improved by adding an organic solvent. Any organic solvent can be used as the organic solvent. For example, alcohols such as methanol, ethanol and propanol, as well as acetone can be used. In consideration of safety, it is preferable to use 30% ethanol as the organic solvent in the method for producing the extract used for the sebaceous gland cell activation inhibitor of the present invention. Distilling off the solvent from the extract gives a paste-like concentrate, and further drying the concentrate gives a dried product.
本発明の抑制剤は、任意の形態の製剤であることができる。本発明の抑制剤は、経口投与製剤として、たとえば糖衣錠、バッカル錠、コーティング錠およびチュアブル錠等の錠剤；トローチ剤；丸剤；散剤；硬カプセル剤および軟カプセル剤を含むカプセル剤；顆粒剤；ならびに懸濁剤、乳剤、シロップ剤およびエリキシル剤等の液剤などであることができる。 The inhibitor of the present invention can be a formulation of any form. The inhibitor of the present invention can be used as an orally administered preparation, for example, tablets such as sugar-coated tablets, buccal tablets, coated tablets and chewable tablets; troches; pills; powders; capsules containing hard capsules and soft capsules; granules; In addition, it can be a liquid agent such as a suspension agent, an emulsion, a syrup agent and an elixir agent.
また、本発明の抑制剤は、静脈注射、皮下注射、腹腔内注射、筋肉内注射、経皮投与、経鼻投与、経肺投与、経腸投与、口腔内投与および経粘膜投与などの非経口投与製剤であることができる。本発明の抑制剤は、たとえば、注射剤、経皮吸収テープ、エアゾール剤および坐剤などであることができる。 In addition, the inhibitor of the present invention is parenteral such as intravenous injection, subcutaneous injection, intraperitoneal injection, intramuscular injection, transdermal administration, nasal administration, transpulmonary administration, enteral administration, oral administration and transmucosal administration. It can be an administration formulation. The inhibitors of the present invention can be, for example, injections, transdermal tapes, aerosols and suppositories.
また、本発明の抑制剤は、外用剤として提供されることができる。本発明の外用剤は、医薬品、医薬部外品および化粧品などであることができる。本発明の外用剤は、皮膚、頭皮、毛髪、粘膜および爪などに適用するための外用剤であることができる。外用剤には、たとえばクリーム剤、軟膏剤、液剤、ゲル剤、ローション剤、乳液剤、エアゾール剤、スティック剤、シートマスク剤、固形剤、泡沫剤、オイル剤およびチック剤等の塗布剤；パップ剤、プラスター剤、テープ剤およびパッチ剤等の貼付剤；並びにスプレー剤などが含まれる。 In addition, the inhibitor of the present invention can be provided as an external preparation. The external preparation of the present invention can be a pharmaceutical product, a quasi drug, a cosmetic product, or the like. The external preparation of the present invention can be an external preparation for application to skin, scalp, hair, mucous membranes, nails and the like. External preparations include, for example, creams, ointments, liquids, gels, lotions, emulsions, aerosols, sticks, sheet masks, solids, foams, oils and ticks; Patches such as agents, plasters, tapes and patches; and sprays and the like are included.
また、本発明の抑制剤は、食用に適した形態であることができ、たとえば固形状、液状、顆粒状、粒状、粉末状、カプセル状、クリーム状およびペースト状などであってもよい。 In addition, the inhibitor of the present invention can be in an edible form, and may be, for example, solid, liquid, granular, granular, powdery, capsule-like, cream-like, paste-like or the like.
本発明はまた、アルクチゲニンおよび／またはアルクチインを有効成分として含有する、皮脂腺細胞の活性化を抑制するための組成物を提供する。本発明の組成物は、上述した抑制剤と同様に構成されることができる。本発明の組成物は、医薬品、医薬部外品、化粧品および食品などに用いるための組成物であることができる。本発明の組成物は、医薬品、医薬部外品、化粧品および食品に通常用いられる任意の成分をさらに含むことができる。たとえば、本発明の組成物は、薬学的に許容される基剤、担体、賦形剤、結合剤、崩壊剤、滑沢剤および着色剤などをさらに含んでもよい。 The present invention also provides a composition containing arctigenin and / or arctiin as an active ingredient for suppressing the activation of sebaceous gland cells. The composition of the present invention can be constructed in the same manner as the above-mentioned inhibitor. The composition of the present invention can be a composition for use in pharmaceuticals, quasi-drugs, cosmetics, foods and the like. The compositions of the present invention may further comprise any ingredient commonly used in pharmaceuticals, quasi-drugs, cosmetics and foods. For example, the compositions of the present invention may further comprise pharmaceutically acceptable bases, carriers, excipients, binders, disintegrants, lubricants and colorants.
本発明の組成物に使用する担体および賦形剤の例には、乳糖、ブドウ糖、白糖、マンニトール、デキストリン、馬鈴薯デンプン、トウモロコシデンプン、炭酸カルシウム、リン酸カルシウム、硫酸カルシウムおよび結晶セルロースなどを含む。 Examples of carriers and excipients used in the compositions of the present invention include lactose, glucose, sucrose, mannitol, dextrin, potato starch, corn starch, calcium carbonate, calcium phosphate, calcium sulfate and crystalline cellulose.
結合剤の例には、デンプン、ゼラチン、シロップ、トラガントゴム、ポリビニルアルコール、ポリビニルエーテル、ポリビニルピロリドン、ヒドロキシプロピルセルロース、メチルセルロース、エチルセルロースおよびカルボキシメチルセルロースなどを含む。 Examples of binders include starch, gelatin, syrup, tragant rubber, polyvinyl alcohol, polyvinyl ether, polyvinylpyrrolidone, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose and the like.
崩壊剤の例には、デンプン、寒天、ゼラチン末、結晶セルロース、炭酸カルシウム、炭酸水素ナトリウム、アルギン酸ナトリウム、カルボキシメチルセルロースナトリウムおよびカルボキシメチルセルロースカルシウムなどを含む。 Examples of disintegrants include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, sodium alginate, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose and the like.
滑沢剤の例には、ステアリン酸マグネシウム、水素添加植物油、タルクおよびマクロゴールなどを含む。着色剤は、医薬品、化粧品および食品に添加することが許容されている任意の着色剤を使用することができる。 Examples of lubricants include magnesium stearate, hydrogenated vegetable oils, talc and macrogol. As the colorant, any colorant that is allowed to be added to pharmaceuticals, cosmetics and foods can be used.
また、本発明の組成物は、必要に応じて、白糖、ゼラチン、精製セラック、ゼラチン、グリセリン、ソルビトール、エチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニルピロリドン、フタル酸セルロースアセテート、ヒドロキシプロピルメチルセルロースフタレート、メチルメタクリレートおよびメタアクリル酸重合体などで一層以上の層で被膜してもよい。 In addition, the composition of the present invention contains, if necessary, sucrose, gelatin, purified cellac, gelatin, glycerin, sorbitol, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, cellulose acetate, hydroxypropyl methyl cellulose phthalate, It may be coated with one or more layers such as methyl methacrylate and methacrylic acid polymer.
また、本発明の組成物は、必要に応じて、pH調節剤、緩衝剤、安定化剤、保存剤、防腐剤、希釈剤、コーティング剤、甘味剤、香料および可溶化剤などを添加してもよい。 Further, the composition of the present invention is added with a pH adjuster, a buffer, a stabilizer, a preservative, a preservative, a diluent, a coating agent, a sweetener, a flavoring agent, a solubilizing agent and the like, if necessary. May be good.
本発明はまた、本発明の組成物を含有する医薬品を提供する。本発明の医薬品は、皮脂腺細胞における脂質の蓄積および皮脂の分泌の亢進または過剰などにより生じる様々な疾患および状態を治療、改善および予防するのに有効であり、皮脂腺細胞の活性化を抑制するための医薬品であることができる。本発明の医薬品は、たとえば、尋常性ざ瘡（にきび）等のざ瘡、ざ瘡様発疹症、アトピー性皮膚炎、酒さ、劇症酒さ、口囲皮膚炎、酒さ様皮膚炎、顔面播種状粟粒性狼瘡、脂漏、脂漏性皮膚炎、マラセチア毛包炎、皮脂欠乏症、面皰母斑、脂腺母斑、脂腺増殖症、多発性脂腺嚢腫、脂腺腺腫および脂腺癌などの疾患および状態を治療、改善または予防するための医薬品であることができる。 The present invention also provides a pharmaceutical product containing the composition of the present invention. The pharmaceutical product of the present invention is effective for treating, ameliorating and preventing various diseases and conditions caused by accumulation of lipids in sebaceous gland cells and increased or excessive secretion of sebum, and suppresses activation of sebaceous gland cells. Can be a drug. The medicament of the present invention includes, for example, acne such as acne vulgaris, acne-like rash, atopic dermatitis, liquor, fulminant liquor, mouth circumference dermatitis, liquor-like dermatitis, Facial disseminated acne, sebaceous gland, sebaceous dermatitis, malacetia folliculitis, sebaceous deficiency, acne acne, sebaceous acne, sebaceous proliferative gland, multiple sebaceous cysts, sebaceous adenomas and sebaceous glands It can be a drug for treating, ameliorating or preventing diseases and conditions such as cancer.
本発明はまた、本発明の組成物を含有する化粧品を提供する。本発明の化粧品は、尋常性ざ瘡（にきび）等のざ瘡、ざ瘡様発疹症、酒さ、劇症酒さ、口囲皮膚炎、酒さ様皮膚炎、顔面播種状粟粒性狼瘡、脂漏、脂漏性皮膚炎、マラセチア毛包炎、皮脂欠乏症、面皰母斑、脂腺母斑、脂腺増殖症、多発性脂腺嚢腫、脂腺腺腫および脂腺癌などの疾患および状態を改善または予防するための化粧品であることができる。また、本発明の化粧品は、脂性肌、脂性フケおよび脂漏性脱毛症などを改善または予防するための化粧品であることができる。 The present invention also provides cosmetics containing the compositions of the present invention. The cosmetics of the present invention include acne such as acne vulgaris, acne-like rash, liquor, fulminant liquor, mouth circumference dermatitis, liquor-like dermatitis, facial disseminated seborrheic wolf. Diseases and conditions such as seborrheic dermatitis, seborrheic dermatitis, maracetia folliculitis, sebaceous deficiency, acne acne, sebaceous acne, sebaceous proliferative gland, multiple sebaceous cysts, sebaceous adenomas and sebaceous cancers It can be a cosmetic for improvement or prevention. In addition, the cosmetic product of the present invention can be a cosmetic product for improving or preventing oily skin, oily dandruff, seborrheic alopecia, and the like.
本発明の化粧品は、たとえば皮膚（顔面、手指および全身など）、頭皮、毛髪、粘膜、爪、まつ毛および／または眉毛等に適用されることができる。本発明の化粧品は、たとえば洗顔クリーム、洗顔フォーム、フェイスクレンジング、固形石鹸、ボディソープおよびハンドソープなどの皮膚洗浄用化粧料；化粧水、乳液、クリーム、ゲル、シートマスク、美容オイルおよび美容液等のスキンケア化粧料；ファンデーション、口紅、フェイスカラー、アイライナーおよび下地用化粧料などのメークアップ化粧料；制汗剤；日焼け止め化粧料；並びにシャンプー、リンスおよびコンディショナーなどの毛髪用洗浄剤；ヘアスプレー、ヘアムース、ヘアフォーム、ヘアオイル、ヘアミスト、ヘアウォーター、ヘアローション、ヘアブロー、ヘアミルク、ヘアクリーム、ヘアトリートメント、ヘアマスク、ヘアジェル、ヘアバーム、ヘアトニックおよびヘアリキッドなどの毛髪または頭皮用化粧料などであることができる。 The cosmetics of the present invention can be applied to, for example, skin (face, fingers and whole body, etc.), scalp, hair, mucous membranes, nails, eyelashes and / or eyebrows. The cosmetics of the present invention include skin cleansing cosmetics such as face wash cream, face wash foam, face cleansing, bar soap, body soap and hand soap; lotion, milky lotion, cream, gel, sheet mask, beauty oil and beauty liquid, etc. Skin Care Cosmetics; Makeup Cosmetics such as Foundations, Lipsticks, Face Colors, Eyeliners and Base Cosmetics; Antiperspirants; Sunscreen Cosmetics; And Hair Cleansers such as Shampoo, Rinse and Conditioner; Hairspray , Hair mousse, hair foam, hair oil, hair mist, hair water, hair lotion, hair blow, hair milk, hair cream, hair treatment, hair mask, hair gel, hair balm, hair tonic and hair liquid cosmetics for hair or scalp etc. it can.
本発明はまた、アルクチゲニンおよび／またはアルクチインを有効成分として含有する皮脂腺細胞の活性化を抑制するための食品組成物を提供する。本発明の食品組成物は、上述した抑制剤および組成物と同様に構成されることができる。本発明の食品組成物は、尋常性ざ瘡（にきび）等のざ瘡、ざ瘡様発疹症、酒さ、劇症酒さ、口囲皮膚炎、酒さ様皮膚炎、顔面播種状粟粒性狼瘡、脂漏、脂漏性皮膚炎、マラセチア毛包炎、皮脂欠乏症、面皰母斑、脂腺母斑、脂腺増殖症、多発性脂腺嚢腫、脂腺腺腫および脂腺癌などの疾患および状態を改善または予防するための食品組成物であることができる。 The present invention also provides a food composition for suppressing the activation of sebaceous gland cells containing arctigenin and / or arctiin as an active ingredient. The food composition of the present invention can be constructed in the same manner as the inhibitor and composition described above. The food composition of the present invention includes acne such as acne vulgaris, acne-like rash, liquor, fulminant liquor, peri-mouth dermatitis, liquor-like dermatitis, and facial disseminated graininess. Diseases such as acne, seborrheic dermatitis, seborrheic dermatitis, maracetia folliculitis, sebaceous deficiency, acne acne, sebaceous gland pimples, sebaceous proliferative disorders, multiple sebaceous cysts, sebaceous adenomas and sebaceous cancers It can be a food composition for improving or preventing the condition.
本明細書において「食品組成物」には、一般的な飲食品だけでなく、病者用食品、健康食品、機能性食品、特定保健用食品、栄養補助食品およびサプリメントなどが含まれる。一般的な飲食品には、たとえば各種飲料、各種食品、加工食品、液状食品（スープ等）、調味料、栄養ドリンクおよび菓子類などが含まれる。本明細書において「加工食品」とは、天然の食材（動物および植物など）に対し加工および／または調理を施したものをいい、たとえば肉加工品、野菜加工品、果実加工品、冷凍食品、レトルト食品、缶詰食品、瓶詰食品およびインスタント食品などが含まれる。本発明の食品組成物は、皮脂腺細胞の活性化を抑制する旨の表示を付した食品であってもよい。また、本発明の食品組成物は、袋および容器等に封入された形態で提供されてもよい。本発明において使用する袋および容器は、食品に通常使用される任意の袋および容器であることができる。 In the present specification, the "food composition" includes not only general foods and drinks but also foods for the sick, health foods, functional foods, foods for specified health uses, dietary supplements and supplements. Common foods and drinks include, for example, various beverages, various foods, processed foods, liquid foods (soups and the like), seasonings, energy drinks and confectionery. As used herein, the term "processed food" refers to natural foodstuffs (animals, plants, etc.) that have been processed and / or cooked, such as processed meat products, processed vegetable products, processed fruit products, and frozen foods. Includes retort foods, canned foods, bottled foods and instant foods. The food composition of the present invention may be a food labeled to suppress the activation of sebaceous gland cells. Further, the food composition of the present invention may be provided in a form enclosed in a bag, a container or the like. The bag and container used in the present invention can be any bag and container normally used for food.
本発明の抑制剤、組成物、医薬品、化粧品および食品組成物におけるアルクチゲニンおよび／またはアルクチインの含有量は、皮脂腺細胞の活性化を抑制する効果を発揮できる量であればよく、適用する対象、目的および投与方法（摂取方法）に応じて適宜設定することができる。たとえばヒトに経口摂取させる場合、好ましくはアルクチゲニンおよび／またはアルクチインを1日あたりの摂取量が10〜2000mgとなるように含むことができる。 The content of arctigenin and / or arctiin in the inhibitor, composition, pharmaceutical product, cosmetics and food composition of the present invention may be an amount capable of exerting an effect of suppressing the activation of sebaceous gland cells, and the object and purpose of application thereof. And it can be appropriately set according to the administration method (intake method). For example, when given orally to humans, it can preferably contain arctigenin and / or arctiin such that the daily intake is 10-2000 mg.
以下に実施例を示し、本発明の実施の形態についてさらに詳しく説明するが、本発明は以下の実施例に限定されるものではない。 Examples are shown below, and embodiments of the present invention will be described in more detail, but the present invention is not limited to the following examples.
（酵素活性の測定）
ゴボウシ中のβ−グルコシダーゼ活性は、以下の方法で測定した。産地やロットが異なるゴボウシをウイレー氏粉砕機により粉砕し、このゴボウシ粉砕品0.1gを10mLの水で希釈し、試料溶液とした。
(Measurement of enzyme activity)
The β-glucosidase activity in burdock was measured by the following method. Burdock from different origins and lots was crushed with a Willey crusher, and 0.1 g of this burdock crushed product was diluted with 10 mL of water to prepare a sample solution.
基質溶液として、p-ニトロフェニル-β-D-グルコピラノシド0.15gに水を加えて25mLに定容し、20mmol/L p-ニトロフェニル-β-D-グルコピラノシド水溶液を調製した。0.1mol/L酢酸緩衝液1mLに20mmol/L p-ニトロフェニル-β-D-グルコピラノシド水溶液0.5mLを加えて、反応混液を調製し、37℃で約5分予備加熱を行った。 As a substrate solution, water was added to 0.15 g of p-nitrophenyl-β-D-glucopyranoside and the volume was adjusted to 25 mL to prepare a 20 mmol / L p-nitrophenyl-β-D-glucopyranoside aqueous solution. A reaction mixture was prepared by adding 0.5 mL of a 20 mmol / L p-nitrophenyl-β-D-glucopyranoside aqueous solution to 1 mL of 0.1 mol / L acetate buffer, and preheating was performed at 37 ° C. for about 5 minutes.
反応混液に試料溶液0.5mL加えて37℃で15分反応させた後、反応停止液である0.2mol/L炭酸ナトリウム水溶液を2mL加えて反応を停止させた。この液の400nmにおける吸光度を測定し、酵素反応を行わないブランク溶液からの変化量から下式により酵素活性を求めた。
酵素活性（U/g）＝（試料溶液の吸光度-ブランク溶液の吸光度）×4mL×1／18.1（p-ニトロフェノールの上記測定条件下でのミリモル分子吸光係数：cm2／μmol)×1／光路長(cm)×1／反応時間（分）×1／0.5mL×1／試料溶液濃度（g／mL）
After adding 0.5 mL of the sample solution to the reaction mixture and reacting at 37 ° C. for 15 minutes, 2 mL of a 0.2 mol / L sodium carbonate aqueous solution as a reaction terminator was added to terminate the reaction. The absorbance of this solution at 400 nm was measured, and the enzymatic activity was determined by the following formula from the amount of change from the blank solution in which the enzymatic reaction was not performed.
Enzyme activity (U / g) = (absorbance of sample solution-absorbance of blank solution) x 4 mL x 1 / 18.1 (mmol molecule extinction coefficient of p-nitrophenol under the above measurement conditions: cm 2 / μmol) x 1 / Optical path length (cm) x 1 / Reaction time (minutes) x 1 / 0.5 mL x 1 / Sample solution concentration (g / mL)
（実施例1 ゴボウシ抽出物の製造1）
本発明の組成物の一実施例として、ゴボウシからエキス（抽出物）を抽出した。ゴボウシ（酵素活性8.23U/g）を切裁し、9.5mmの篩を全通するものをさらに0.85mmの篩に通し、75％が残ることを確認した。このゴボウシ細切80kgを29〜33℃に保温した水560Lに加えて30分間攪拌した。次いで、エタノール265Lを加えて85℃に昇温し、さらに60分間加熱還流した。この溶液を遠心分離し、ゴボウシ抽出液を得た。この操作を2回繰り返して得られた抽出液を合わせて、減圧濃縮し、抽出物固形分に対してデキストリン20％を加えて、噴霧乾燥した。アルクチゲニンおよびアルクチイン含量は、それぞれ6.2％および7.1％であり、アルクチゲニン／アルクチイン（重量比）＝0.89のゴボウシ抽出物粉末（デキストリン20％含有）が得られた。
(Example 1 Production of burdock extract 1)
As an example of the composition of the present invention, an extract (extract) was extracted from burdock. Burdock (enzyme activity 8.23 U / g) was cut and passed through a 9.5 mm sieve and further passed through a 0.85 mm sieve, and it was confirmed that 75% remained. 80 kg of this burdock shred was added to 560 L of water kept at 29 to 33 ° C, and the mixture was stirred for 30 minutes. Then, 265 L of ethanol was added to raise the temperature to 85 ° C., and the mixture was heated under reflux for another 60 minutes. This solution was centrifuged to obtain a burdock extract. The extracts obtained by repeating this operation twice were combined, concentrated under reduced pressure, 20% of dextrin was added to the solid content of the extract, and the mixture was spray-dried. The contents of arctigenin and arctiin were 6.2% and 7.1%, respectively, and burdock extract powder (containing 20% dextrin) having arctigenin / arctiin (weight ratio) = 0.89 was obtained.
（実施例2 ゴボウシ抽出物の製造2）
本発明の組成物の一実施例として、ゴボウシからエキス（抽出物）を抽出した。ゴボウシ（酵素活性8.23U/g）を切裁し、9.5mmの篩を全通するものをさらに0.85mmの篩に通し、75％が残ることを確認した。このゴボウシ細切80kgを30〜33℃に保温した水560Lに加えて30分間攪拌した後、エタノール265Lを加えて85℃に昇温し、さらに30分間加熱還流した。この溶液を遠心分離し、ゴボウシ抽出液を得た。この操作を2回繰り返して得られた抽出液を合わせて、減圧濃縮し、抽出物固形分に対してデキストリン20％を加えて、噴霧乾燥した。アルクチゲニンおよびアルクチイン含量は、それぞれ6.0％および6.8％であり、アルクチゲニン／アルクチイン（重量比）＝0.87のゴボウシ抽出物粉末（デキストリン20％含有）が得られた。
(Example 2 Production of burdock extract 2)
As an example of the composition of the present invention, an extract (extract) was extracted from burdock. Burdock (enzyme activity 8.23 U / g) was cut and passed through a 9.5 mm sieve and further passed through a 0.85 mm sieve, and it was confirmed that 75% remained. 80 kg of this burdock shred was added to 560 L of water kept at 30 to 33 ° C. and stirred for 30 minutes, then 265 L of ethanol was added to raise the temperature to 85 ° C., and the mixture was heated under reflux for another 30 minutes. This solution was centrifuged to obtain a burdock extract. The extracts obtained by repeating this operation twice were combined, concentrated under reduced pressure, 20% of dextrin was added to the solid content of the extract, and the mixture was spray-dried. The contents of arktigenin and alktiine were 6.0% and 6.8%, respectively, and burdock extract powder (containing 20% dextrin) having arktigenin / alktiin (weight ratio) = 0.87 was obtained.
（実施例3 ゴボウシ抽出物の製造3）
本発明の組成物の一実施例として、ゴボウシからエキス（抽出物）を抽出した。ゴボウシ（酵素活性7.82U/g）を切裁し、9.5mmの篩を全通するものをさらに0.85mmの篩に通し、75％が残ることを確認した。このゴボウシ細切80kgを30〜32℃に保温した水560Lに加えて40分間攪拌した後、60分後にエタノール258Lを加えて85℃に昇温し、さらに30分間加熱還流した。この液を遠心分離し、ゴボウシ抽出液を得た。この操作を2回繰り返して得られた抽出液を合わせて、減圧濃縮し、抽出物固形分に対してデキストリン20％を加えて、噴霧乾燥した。アルクチゲニンおよびアルクチイン含量は、それぞれ6.2％および6.7％であり、アルクチゲニン／アルクチイン（重量比）＝0.93のゴボウシ抽出物粉末（デキストリン20％含有）が得られた。
(Example 3 Production of burdock extract 3)
As an example of the composition of the present invention, an extract (extract) was extracted from burdock. Burdock (enzyme activity 7.82 U / g) was cut and passed through a 9.5 mm sieve and further passed through a 0.85 mm sieve, and it was confirmed that 75% remained. 80 kg of this burdock shred was added to 560 L of water kept at 30 to 32 ° C. and stirred for 40 minutes. After 60 minutes, 258 L of ethanol was added to raise the temperature to 85 ° C., and the mixture was heated under reflux for another 30 minutes. This solution was centrifuged to obtain a burdock extract. The extracts obtained by repeating this operation twice were combined, concentrated under reduced pressure, 20% of dextrin was added to the solid content of the extract, and the mixture was spray-dried. The contents of arktigenin and alktiine were 6.2% and 6.7%, respectively, and burdock extract powder (containing 20% dextrin) with arktigenin / alktiin (weight ratio) = 0.93 was obtained.
（実施例4 ゴボウシ抽出物の製造4）
本発明の組成物の一実施例として、ゴボウシからエキス（抽出物）を抽出した。ゴボウシ（酵素活性7.82U/g）を切裁し、9.5mmの篩を全通するものをさらに0.85mmの篩に通し、75％が残ることを確認した。このゴボウシ細切80kgを30〜32℃に保温した水560Lに加えて30分間攪拌した後、エタノール253Lを加えて85℃に昇温し、さらに40分間加熱還流した。この液を遠心分離し、得られた抽出液を得た。この操作を2回繰り返して得られた抽出液を合わせて、減圧濃縮し、抽出物固形分に対してデキストリン25％を加えて、噴霧乾燥した。アルクチゲニンおよびアルクチイン含量は、それぞれ6.4％および7.2％であり、アルクチゲニン／アルクチイン（重量比）＝0.89のゴボウシ抽出物粉末（デキストリン25％含有）が得られた。
(Example 4 Production of burdock extract 4)
As an example of the composition of the present invention, an extract (extract) was extracted from burdock. Burdock (enzyme activity 7.82 U / g) was cut and passed through a 9.5 mm sieve and further passed through a 0.85 mm sieve, and it was confirmed that 75% remained. 80 kg of this burdock shred was added to 560 L of water kept at 30 to 32 ° C. and stirred for 30 minutes, then 253 L of ethanol was added to raise the temperature to 85 ° C., and the mixture was heated under reflux for another 40 minutes. This liquid was centrifuged to obtain the obtained extract. The extracts obtained by repeating this operation twice were combined, concentrated under reduced pressure, 25% of dextrin was added to the solid content of the extract, and the mixture was spray-dried. The contents of arktigenin and alktiine were 6.4% and 7.2%, respectively, and burdock extract powder (containing 25% dextrin) with arktigenin / alktiin (weight ratio) = 0.89 was obtained.
（実施例5 シナレンギョウ葉抽出物の製造1）
本発明の組成物の一実施例として、シナレンギョウ葉からエキス（抽出物）を抽出した。アルクチイン2.53％およびアルクチゲニン0.76％を含有するレンギョウ葉小刻み50gに水350mLを加えて37℃で30分間保温後、エタノール150mLを添加し30分間加熱抽出した。この溶液を、100メッシュ篩を用いて固液分離し、凍結乾燥を行うことにより、アルクチゲニン含量が5.62％のシナレンギョウ葉抽出物18.62gを得た。
(Example 5 Production of Forsythia viridis leaf extract 1)
As an example of the composition of the present invention, an extract (extract) was extracted from the leaves of Forsythia viridis. 350 mL of water was added to 50 g of forsythia leaf chopped containing 2.53% of arctiin and 0.76% of arctigenin, and the mixture was kept warm at 37 ° C. for 30 minutes, and then 150 mL of ethanol was added and heat-extracted for 30 minutes. This solution was solid-liquid separated using a 100-mesh sieve and freeze-dried to obtain 18.62 g of Forsythia viridis leaf extract having an arctigenin content of 5.62%.
（実施例6 シナレンギョウ葉抽出物の製造2）
本発明の組成物の一実施例として、シナレンギョウ葉からエキス（抽出物）を抽出した。アルクチイン7.38％およびアルクチゲニン0.78％を含有するレンギョウ葉小刻み720gに水5Lを加えて37°Cで30分間保温後、エタノール2.16Lを添加し30分間加熱抽出した。この溶液を、100メッシュ篩を用いて固液分離し、凍結乾燥を行うことにより、アルクチゲニン含量が9.55％のシナレンギョウ葉抽出物343.07gを得た。
(Example 6 Production of Forsythia viridis leaf extract 2)
As an example of the composition of the present invention, an extract (extract) was extracted from the leaves of Forsythia viridis. Forsythia leaf chopped 720 g containing 7.38% arctiine and 0.78% arctigenin was added with 5 L of water and kept warm at 37 ° C for 30 minutes, then 2.16 L of ethanol was added and heat-extracted for 30 minutes. This solution was solid-liquid separated using a 100-mesh sieve and freeze-dried to obtain 343.07 g of Forsythia viridis leaf extract having an arctigenin content of 9.55%.
（実施例7 ゴボウシ抽出物粉末配合顆粒剤）
本発明の組成物の一実施例として、ゴボウシ抽出物を用いて顆粒剤を製造した。「日局」製剤総則、顆粒剤の項に準じて顆粒剤を製造した。すなわち、下記（1）〜（3）の成分をとり、顆粒状に製した。これを1.5ｇずつアルミラミネートフィルムに充填し、1包あたりゴボウシ抽出物粉末を0.5ｇ含有する顆粒剤を得た。
（1）実施例2のゴボウシ抽出物粉末 33.3％
（2）乳糖 65.2％
（3）ヒドロキシプロピルセルロース 1.5％
合計 100％
(Example 7 Burdock extract powder-blended granules)
As an example of the composition of the present invention, granules were produced using burdock extract. Granules were manufactured according to the "Japan Bureau" general rules for formulations and the section on granules. That is, the following components (1) to (3) were taken and made into granules. Each 1.5 g of this was filled in an aluminum laminate film to obtain a granule containing 0.5 g of burdock extract powder per packet.
(1) Burdock extract powder of Example 2 33.3%
(2) Lactose 65.2%
(3) Hydroxypropyl cellulose 1.5%
100% in total
（実施例8 ゴボウシ抽出物粉末配合顆粒剤）
本発明の組成物の一実施例として、ゴボウシ抽出物を用いて顆粒剤を製造した。「日局」製剤総則、顆粒剤の項に準じて顆粒剤を製造した。すなわち、下記（1）〜（3）の成分をとり、顆粒状に製した。これを3.0ｇずつアルミラミネートフィルムに充填し、1包あたりゴボウシ抽出物粉末を2ｇ含有する顆粒剤を得た。
（1）実施例2のゴボウシ抽出物粉末 66.7％
（2）乳糖 30.3％
（3）ヒドロキシプロピルセルロース 3.0％
合計 100％
(Example 8 burdock extract powder-blended granules)
As an example of the composition of the present invention, granules were produced using burdock extract. Granules were manufactured according to the "Japan Bureau" general rules for formulations and the section on granules. That is, the following components (1) to (3) were taken and made into granules. 3.0 g of this was filled in an aluminum laminate film to obtain granules containing 2 g of burdock extract powder per packet.
(1) Burdock extract powder of Example 2 66.7%
(2) Lactose 30.3%
(3) Hydroxypropyl cellulose 3.0%
100% in total
（実施例9 ゴボウシ抽出物粉末配合錠剤）
本発明の組成物の一実施例として、ゴボウシ抽出物を用いて錠剤を製造した。「日局」製剤総則、錠剤の項に準じて錠剤を製した。すなわち、下記（1）〜（6）の成分をとり、錠剤を得た。
（1）実施例2のゴボウシ抽出物粉末 37.0％
（2）結晶セルロース 45.1％
（3）カルメロースカルシウム 10.0％
（4）クロスポピドン 3.5％
（5）含水二酸化ケイ素 3.4％
（6）ステアリン酸マグネシウム 1.0％
合計 100％
(Example 9 Burdock extract powder-blended tablet)
As an example of the composition of the present invention, tablets were produced using burdock extract. Tablets were prepared according to the "Japan Bureau" general rules for formulations and the section on tablets. That is, the following components (1) to (6) were taken to obtain tablets.
(1) Burdock extract powder of Example 2 37.0%
(2) Crystalline cellulose 45.1%
(3) Carmellose calcium 10.0%
(4) Cross popidone 3.5%
(5) Hydrous silicon dioxide 3.4%
(6) Magnesium stearate 1.0%
100% in total
〔アルクチゲニンの皮脂腺細胞の活性化抑制作用〕
（ハムスター皮脂線細胞の培養）
細胞は、ハムスター皮脂腺細胞（クラボウ、KB-4009）を用いた。無菌下（クリーンベンチ内）で、1×104cells/cm2（生細胞数）の密度で細胞をHuMedia-BG培地（クラボウ社、KB-2150）に接種し、37℃で24時間培養した。24時間後、培地を交換した。70〜80%コンフルエントで継代培養を行った。細胞が十分に増えたところで、2.5×104cells/cm2の密度で、24ウェルプレートに500μLずつ、細胞懸濁液を接種した。プレートを37℃のインキュベーターに入れ、24時間培養した。細胞が十分にコンフルエントになったら、さらに2〜3日培養の上、HuMedia-BG（クラボウ、KB-2150）をHuMedia-BD（クラボウ、KB-2250）（以後、これら培地を「アッセイ培地」と呼ぶ。）に交換し、分化誘導を開始した。分化誘導開始と同時に、アルクチゲニン（ゴボウシから精製）を各濃度（0.1、10、25、50μＭ）に調整し処理した。アルクチゲニンは、それぞれジメチルスルホキシドに溶解し、全てのサンプルにおいてジメチルスルホキシド濃度0.1％になるように処理した。対照サンプルとして、溶媒のみを処理したものを用いた。処理培地は、1日おきに交換し、13〜14日間培養を続けた。
[Arctigenin's inhibitory effect on sebaceous gland cell activation]
(Culture of hamster sebum line cells)
As cells, hamster sebaceous gland cells (Kurabo Industries, KB-4009) were used. Under aseptic conditions (in a clean bench), cells were inoculated into HuMedia-BG medium (Krabou, KB-2150) at a density of 1 × 10 4 cells / cm 2 (number of viable cells) and cultured at 37 ° C. for 24 hours. .. After 24 hours, the medium was changed. Subculture was performed at 70-80% confluent. When the cells were sufficiently grown, a 24-well plate was inoculated with 500 μL of cell suspension at a density of 2.5 × 10 4 cells / cm 2. The plate was placed in an incubator at 37 ° C. and cultured for 24 hours. When the cells are sufficiently confluent, culture for another 2-3 days and then HuMedia-BG (Kurabo, KB-2150) to HuMedia-BD (Kurabo, KB-2250) (hereinafter, these media are referred to as "assay medium". It was exchanged for (call) and induction of differentiation was started. At the same time as the initiation of differentiation induction, arctigenin (purified from burdock) was adjusted to each concentration (0.1, 10, 25, 50 μM) and treated. Arctigenin was each dissolved in dimethyl sulfoxide and treated to a dimethyl sulfoxide concentration of 0.1% in all samples. As a control sample, a sample treated with only a solvent was used. The treatment medium was changed every other day and the culture was continued for 13-14 days.
（細胞数の測定）
細胞数の測定は、脂質合成測定キット（クラボウ、SE-3001）を用いて行った。細胞数測定溶液WST-8は、WST-8、1-メトキシ-5-メチルフェナジニウムメチル硫酸塩および塩化ナトリウムの成分からなる。WST-8は新規テトラゾリウム塩で、細胞内脱水素酵素により還元され、水溶性のホルマザンを生成する。このホルマザンを450nmの吸光度で直接測定することにより、容易に生細胞数を計測することができる。0.6mlの細胞数測定溶液WST-8を培地にて25倍希釈した。24ウェルプレートの各ウェルの培地を除去し、希釈した細胞数測定溶液を0.5mlずつ各ウェルに添加し、30分間37℃でインキュベートした。0.2ml／ウェルの上清を96ウェルプレートに移し、450nmの波長で吸光度を測定した。
(Measurement of cell number)
The cell number was measured using a lipid synthesis measurement kit (Kurabo Industries, SE-3001). Cell numbering solution WST-8 consists of WST-8, 1-methoxy-5-methylphenazineium methylsulfate and sodium chloride. WST-8 is a novel tetrazolium salt that is reduced by intracellular dehydrogenase to produce water-soluble formazan. By directly measuring this formazan with an absorbance of 450 nm, the number of living cells can be easily measured. 0.6 ml of cell number measurement solution WST-8 was diluted 25-fold with medium. The medium in each well of the 24-well plate was removed, 0.5 ml of the diluted cell number measurement solution was added to each well, and the mixture was incubated at 37 ° C. for 30 minutes. The 0.2 ml / well supernatant was transferred to a 96-well plate and the absorbance was measured at a wavelength of 450 nm.
（脂肪滴の染色）
脂肪滴の染色は、脂質合成測定キット（クラボウ、SE-3001）を用いて行った。オイルレッドO原液9mlとオイルレッドO希釈液6mlを混合し、ろ過用フィルター「ニューステラディスク」（0.45μm）を用いてろ過した。細胞数を測定した各ウェルの細胞数測定溶液を除去し、PBS(-)緩衝液を0.5ml添加した。上清を除去し、PBS(-)緩衝液0.5mlを添加し、細胞を2回洗浄した。上清を除去し、10%ホルマリン溶液を0.5ml添加し、10分間室温で静置し、細胞を固定した。上清を除去し、PBS(-)緩衝液を0.5ml添加した（細胞を2回洗浄した）。上清を除去し、60％イソプロパノールを0.5ml添加し、1分間室温で静置した。上清を除去し、調製したオイルレッドO溶液を0.3ml添加し、30分間室温で静置した。上清を除去し、60％イソプロパノールを0.5ml添加した（細胞を2回洗浄した）。上清を除去し、PBS(-)緩衝液を0.5ml添加し、染色された脂質の顕微鏡画像を撮影した。
(Staining of fat droplets)
Lipid droplets were stained using a lipid synthesis measurement kit (Kurabo Industries, SE-3001). 9 ml of Oil Red O stock solution and 6 ml of Oil Red O diluted solution were mixed and filtered using a filtration filter "New Stella Disc" (0.45 μm). The cell numbering solution of each well for which the cell number was measured was removed, and 0.5 ml of PBS (-) buffer was added. The supernatant was removed, 0.5 ml of PBS (-) buffer was added, and the cells were washed twice. The supernatant was removed, 0.5 ml of 10% formalin solution was added, and the cells were allowed to stand at room temperature for 10 minutes to fix the cells. The supernatant was removed and 0.5 ml of PBS (-) buffer was added (cells were washed twice). The supernatant was removed, 0.5 ml of 60% isopropanol was added, and the mixture was allowed to stand at room temperature for 1 minute. The supernatant was removed, 0.3 ml of the prepared Oil Red O solution was added, and the mixture was allowed to stand at room temperature for 30 minutes. The supernatant was removed and 0.5 ml of 60% isopropanol was added (cells were washed twice). The supernatant was removed, 0.5 ml of PBS (-) buffer was added, and microscopic images of the stained lipids were taken.
（脂肪滴の直径を測定する方法）
染色された脂質の顕微鏡画像を用いて、脂肪滴の直径を測定した。脂肪滴の直径の測定方法について、図1を用いて説明する。1つの処理は、3つのウェルにて行った。1つのウェルにつき、脂肪滴形成が顕著に見られる2つの区画を選択して200倍にて撮影した。撮影した画像中の脂肪滴の大きいものから10個選択し、それぞれの脂肪滴の大きさを測定した。すなわち、1つの処理につき、脂肪滴60個の直径を測定し、その平均値を脂肪滴の大きさとした。
(Method of measuring the diameter of fat droplets)
The diameter of the lipid droplet was measured using a microscopic image of the stained lipid. A method for measuring the diameter of a lipid droplet will be described with reference to FIG. One treatment was performed in 3 wells. For each well, two compartments with marked lipid droplet formation were selected and photographed at 200x magnification. Ten of the large fat droplets in the captured image were selected, and the size of each fat droplet was measured. That is, the diameter of 60 lipid droplets was measured for one treatment, and the average value was taken as the size of the lipid droplets.
（試験1：アルクチゲニンの皮脂腺細胞に対する細胞毒性）
上述した方法を用いて、皮脂腺細胞を各種の濃度のアルクチゲニンで処理し、細胞毒性を評価した。アルクチゲニンで処理した場合に、皮脂腺細胞の生細胞数の減少は見られなかった（図示せず）。したがって、アルクチゲニンは、皮脂腺細胞に対する細胞毒性を有しないことが示された。この結果から、以下の試験において示される脂質合成の抑制は、アルクチゲニン処理による皮脂腺細胞数の減少によるものではないことが確認できた。
(Test 1: Cytotoxicity of arctigenin to sebaceous gland cells)
Sebaceous gland cells were treated with various concentrations of arctigenin using the method described above to evaluate cytotoxicity. No reduction in the viable number of sebaceous gland cells was observed when treated with arctigenin (not shown). Therefore, it was shown that arctigenin has no cytotoxicity to sebaceous gland cells. From this result, it was confirmed that the suppression of lipid synthesis shown in the following tests was not due to the decrease in the number of sebaceous gland cells due to the treatment with arctigenin.
（試験2：脂肪滴形成に対する抑制効果）
上述した方法により皮脂腺細胞を各種の濃度のアルクチゲニン（ゴボウシより精製）で処理し、皮脂腺細胞内で形成された脂肪滴の直径を測定した。図2は、皮脂腺細胞をアルクチゲニンで処理したときの脂肪滴の直径（長さ）を示すグラフである。また、図3は、皮脂腺細胞における染色された脂質の顕微鏡画像を表す図である。
(Test 2: Inhibitory effect on lipid droplet formation)
Sebaceous gland cells were treated with various concentrations of arctigenin (purified from burdock) by the method described above, and the diameter of lipid droplets formed in the sebaceous gland cells was measured. FIG. 2 is a graph showing the diameter (length) of lipid droplets when sebaceous gland cells are treated with arctigenin. In addition, FIG. 3 is a diagram showing a microscopic image of stained lipids in sebaceous gland cells.
図2および図3に示すように、アルクチゲニンで処理することにより、皮脂腺細胞内で形成された脂肪滴の大きさが有意に減少した。また、図2および図3より、アルクチゲニンが濃度依存的に脂質合成を抑制することが示された。したがって、アルクチゲニンは、皮脂腺細胞内で形成される脂肪滴の大きさを減少させる作用を有することが示された。 As shown in FIGS. 2 and 3, treatment with arctigenin significantly reduced the size of the lipid droplets formed in the sebaceous gland cells. In addition, FIGS. 2 and 3 show that arctigenin suppresses lipid synthesis in a concentration-dependent manner. Therefore, arctigenin has been shown to have the effect of reducing the size of lipid droplets formed within the sebaceous gland cells.
以上の結果から、アルクチゲニンが皮脂腺細胞の活性化を抑制する作用を有することが示された。 From the above results, it was shown that arctigenin has an action of suppressing the activation of sebaceous gland cells.
本発明の皮脂腺細胞の活性化の抑制剤、皮脂腺細胞の活性化を抑制するための組成物および皮脂腺細胞の活性化を抑制するための食品組成物は、皮脂腺細胞の活性化により生じる様々な疾患や症状を治療、改善および予防するための医薬品、化粧品および食品に好適に利用することができる。 The agent for suppressing the activation of sebaceous gland cells, the composition for suppressing the activation of sebaceous gland cells, and the food composition for suppressing the activation of sebaceous gland cells of the present invention are various diseases caused by the activation of sebaceous gland cells. It can be suitably used for pharmaceuticals, cosmetics and foods for treating, ameliorating and preventing symptoms and symptoms.
Claims (6)
The food composition according to claim 5, wherein the arktigenin and / or alktiin is contained as burdock, burdock, burdock sprout or forsythia or an extract extracted from these.
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