JP2010024211A - Cell proliferation promoting agent - Google Patents
Cell proliferation promoting agent Download PDFInfo
- Publication number
- JP2010024211A JP2010024211A JP2008190516A JP2008190516A JP2010024211A JP 2010024211 A JP2010024211 A JP 2010024211A JP 2008190516 A JP2008190516 A JP 2008190516A JP 2008190516 A JP2008190516 A JP 2008190516A JP 2010024211 A JP2010024211 A JP 2010024211A
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- extract
- skin
- cell growth
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- added
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Landscapes
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Abstract
Description
本発明は細胞増殖促進剤に関し、さらに詳しくは、極めて高い細胞増殖を促進させる作用を有する細胞増殖促進剤に関する。 The present invention relates to a cell growth promoter, and more particularly to a cell growth promoter having an action of promoting extremely high cell growth.
皮膚の表皮及び真皮は、表皮細胞、線維芽細胞及びこれらの細胞の外にあって皮膚構造を支持するコラーゲンなどの細胞外マトリックスにより構成されている。中でも、年齢の若い皮膚においては、線維芽細胞の増殖が活発で、これら皮膚組織の相互作用が恒常性を保つことにより水分保持、柔軟性、弾力性等が確保され、肌は外見的にも張りや艶があってみずみずしい状態に維持される。 The epidermis and dermis of the skin are composed of epidermal cells, fibroblasts and an extracellular matrix such as collagen that is outside these cells and supports the skin structure. Above all, in younger skin, fibroblasts are actively proliferating, and these skin tissue interactions maintain homeostasis, ensuring moisture retention, flexibility, elasticity, etc. It is kept fresh with tension and gloss.
ところが、紫外線の照射、空気の著しい乾燥、過度の皮膚洗浄等、ある種の外的因子の影響があったり、加齢が進んだりすると、肌に老徴が表れ、線維芽細胞の増殖能も低下する。その結果、皮膚の保湿機能や弾力性が低下し、角質は異常剥離を始め、肌は張りや艶を失い、荒れ、シワ等の老化症状を呈するようになってしまうという問題がある。 However, when there is an influence of certain external factors such as ultraviolet irradiation, drastic air drying, excessive skin washing, etc., or when aging progresses, senile appears on the skin and fibroblast proliferation ability also increases. descend. As a result, there is a problem that the skin moisturizing function and elasticity are lowered, the exfoliation of the keratin begins to be abnormally peeled, the skin loses its tension and gloss, and exhibits aging symptoms such as roughness and wrinkles.
このように、皮膚の老化に伴う変化、即ち、シワ、くすみ、きめの消失、弾力性の低下などには、線維芽細胞の増殖能低下が深く関与していることが知られている。
このため、線維芽細胞の増殖を促進し、皮膚の老化防止や皮膚の老化改善作用を有し、安全性の高い天然物系の細胞増殖促進剤について種々の提案がなされている。例えば、五斂子(Averrhoa carambola L.)の葉部からの抽出物(例えば、特許文献1参照)、ハス胚芽の抽出物(例えば、特許文献2参照)、有色素米又は有色素米の糠の抽出物(例えば、特許文献3参照)、カエデ属イロハモミジの抽出物(例えば、特許文献4参照)、アロエベラ、アーモンド、エノキタケ等の抽出物(例えば、特許文献5参照)、キヨウニン、パッションフラワー、甘草、メリロート、エキナセア等の植物の抽出物(例えば、特許文献6参照)などが提案されている。
また細胞の増殖促進能を有することは、関節炎の予防治療や熱傷の初期治療等にも有用であり、抗老化を目的とした皮膚外用剤への適用以外にも種々の用途が可能である。
Thus, it is known that a decrease in the proliferative ability of fibroblasts is deeply involved in changes accompanying skin aging, that is, wrinkles, dullness, disappearance of texture, and decrease in elasticity.
For this reason, various proposals have been made on natural cell growth promoters that promote the proliferation of fibroblasts, have the effect of preventing skin aging and improving skin aging, and are highly safe. For example, an extract from a leaf portion of Averhoa carambola L. (for example, see Patent Document 1), an extract of lotus germ (for example, see Patent Document 2), pigmented rice, or rice with pigmented rice Extracts (for example, see Patent Document 3), extracts of maple genus maple (for example, see Patent Document 4), extracts such as aloe vera, almond, enokitake (for example, see Patent Document 5), kiyonin, passion flower, Extracts of plants such as licorice, merirot and echinacea (for example, see Patent Document 6) have been proposed.
In addition, the ability to promote cell growth is useful for arthritis prevention treatment, initial treatment for burns, and the like, and can be used for various purposes other than application to an external skin preparation for anti-aging purposes.
しかしながら、前記抽出物において線維芽細胞の増殖を促進する具体的な化合物は未だ特定されておらず、更なる高い線維芽細胞の増殖促進効果を有する天然系の線維芽細胞増殖促進剤の提供が強く望まれているのが現状である。 However, a specific compound that promotes fibroblast proliferation in the extract has not yet been specified, and there is a need to provide a natural fibroblast proliferation promoter having a higher fibroblast proliferation promoting effect. The current situation is strongly desired.
本発明は以上述べたような従来の事情に対処してなされたもので、高い細胞増殖促進作用を有する細胞増殖促進剤を提供することを目的とする。 The present invention has been made in response to the conventional circumstances as described above, and an object thereof is to provide a cell growth promoting agent having a high cell growth promoting action.
本発明は、マメ科シカクマメ(Psophocarpus)属に属する植物の中から選ばれる1種または2種以上の植物の抽出物よりなることを特徴とする細胞増殖促進剤である。
また本発明によれば、マメ科シカクマメ(Psophocarpus)属に属する植物の中から選ばれる1種または2種以上の植物の抽出物よりなることを特徴とするTGF−β産生促進剤、コラーゲンゲル収縮促進剤およびインテグリン産生促進剤が提供される。
The present invention is a cell growth promoter comprising an extract of one or more plants selected from plants belonging to the genus Psophocarpus.
Further, according to the present invention, a TGF-β production promoter, collagen gel contraction, comprising an extract of one or more plants selected from plants belonging to the genus Psophocarpus. Accelerators and integrin production promoters are provided.
ここで、TGF−βとは、細胞増殖・分化を制御し、生体の恒常性を維持するサイトカイン(細胞の働きを調節する分泌性タンパク)の一種で、生体のほぼあらゆる臓器や組織で発現しているものである。
すなわちTGF−βは、細胞の分化・遊走・接着に密接に関与し、個体発生や組織再構築、創傷治癒、炎症・免疫、癌の浸潤・転移などの幅広い領域で重要な役割を果たしている。大腸や膵臓、胃等の消化器癌や白血病等の癌において、TGF−β、TGF−βの受容体、TGF−βのシグナル伝達分子(Smad)の遺伝子変異による機能異常が報告されている。TGF−βによる細胞の増殖制御(抑制)が、ヒトの細胞では重要な生理的ブレーキになっているが、そのブレーキの故障が、異常な細胞増殖反応、すなわち癌化につながると考えられている。
またTGF−βがアトピー性皮膚炎や喘息などの乳幼児のアレルギー性疾患や感染症の発症を抑制する可能性が指摘されている(Kalliomaki M et al. : J Allergy Clin Immunol 104(6):1251-7, 1999, Oddy WH et al. : J Allergy Clin Immunol 112(4):723-8, 2003.)。
さらに経口的なTGF−βの投与によってアレルギー反応が選択的に抑制できることも知られている(特願2005−252912号、Okamoto A et al. : Int Immunol. 17(6):705-12, 2005)。
Here, TGF-β is a type of cytokine (a secreted protein that regulates cell functions) that controls cell proliferation and differentiation and maintains homeostasis, and is expressed in almost all organs and tissues of the living body. It is what.
That is, TGF-β is closely involved in cell differentiation / migration / adhesion, and plays an important role in a wide range of areas such as ontogeny, tissue reconstruction, wound healing, inflammation / immunity, cancer invasion / metastasis. In cancers of digestive organs such as the large intestine, pancreas, and stomach, and cancers such as leukemia, functional abnormalities have been reported due to gene mutations in TGF-β, TGF-β receptors, and TGF-β signaling molecules (Smad). Cell growth control (suppression) by TGF-β is an important physiological brake in human cells, but failure of the brake is thought to lead to an abnormal cell growth reaction, that is, canceration. .
It has also been pointed out that TGF-β may suppress the onset of allergic diseases and infections in infants such as atopic dermatitis and asthma (Kalliomaki M et al.: J Allergy Clin Immunol 104 (6): 1251). -7, 1999, Oddy WH et al .: J Allergy Clin Immunol 112 (4): 723-8, 2003.).
Furthermore, it is known that allergic reaction can be selectively suppressed by oral administration of TGF-β (Japanese Patent Application No. 2005-252912, Okamoto A et al .: Int Immunol. 17 (6): 705-12, 2005. ).
コラーゲンゲル収縮については、創傷治癒のモデル系とされており、コラーゲンゲル収縮の程度は、細胞の運動活性を反映し、様々な細胞増殖因子やサイトカイン類等により促進される 。したがってコラーゲンゲル収縮促進剤は、創傷治癒、皮膚潰瘍、ケロイドといった難治性皮膚疾患の治療、あるいは皮膚移植の際に、移植片の定着を促すための薬剤として利用可能である。 Collagen gel contraction is considered to be a model system for wound healing, and the degree of collagen gel contraction reflects the motor activity of cells and is promoted by various cell growth factors and cytokines. Therefore, the collagen gel contraction promoter can be used as a drug for promoting the fixation of a graft in the treatment of intractable skin diseases such as wound healing, skin ulcer and keloid, or in skin transplantation.
インテグリンは、細胞表面タンパク質のひとつで、主に細胞外マトリックスへの細胞接着、細胞外マトリックスからの情報伝達に関与する細胞接着分子である。α鎖とβ鎖の2つのサブユニットからなるヘテロダイマーである。
インテグリンは細胞外マトリックス成分であるフィブロネクチンやラミニンのリガンドと結合し、細胞の接着、遊走に関与している。したがってインテグリンの産生を高めることは組織構造の安定化剤や創傷治癒促進剤として働くことが期待される。また細胞内領域で様々なシグナル伝達因子やアクチン結合蛋白質と直接あるいは間接的に結合し、細胞外マトリックスに書き込まれた情報を細胞内に伝達する役割を果たしている。
さらに血管傷害時に血小板凝集作用により正常化させる際や、白血球が血管外の組織に遊走して浸潤し、損傷した組織を破壊したり、異物を貪食したりする場合にもインテグリンファミリーが関与している。
Integrin is one of cell surface proteins and is a cell adhesion molecule mainly involved in cell adhesion to the extracellular matrix and signal transmission from the extracellular matrix. It is a heterodimer composed of two subunits, α chain and β chain.
Integrins bind to ligands of fibronectin and laminin, which are extracellular matrix components, and are involved in cell adhesion and migration. Therefore, increasing integrin production is expected to work as a tissue structure stabilizer and wound healing promoter. It also binds directly or indirectly to various signal transduction factors and actin-binding proteins in the intracellular region, and plays a role in transmitting information written in the extracellular matrix into the cell.
The integrin family is also involved when normalizing by platelet aggregation during vascular injury, or when leukocytes migrate to and invade extravascular tissues, destroying damaged tissues or phagocytosing foreign bodies. Yes.
本発明の細胞増殖促進剤は、細胞増殖促進作用に優れたものである。また、本発明の細胞増殖促進剤は、例えば基礎化粧料、薬用化粧料、医薬品製剤などに適用することができ、細胞増殖促進効果が著しく改良された安全性の高いものである。
本発明のTGF−β産生促進剤は、TGF−βの産生を促進させることにより、細胞増殖・分化を制御し、生体の恒常性を維持することができる。
本発明のコラーゲンゲル収縮促進剤は、コラーゲンゲルの収縮を促進させることにより、創傷治癒、皮膚潰瘍、ケロイドといった難治性皮膚疾患の治療、あるいは皮膚移植の際に、移植片の定着を促すことができる。
本発明のインテグリン産生促進剤は、インテグリンの産生を促進させることにより、組織構造の安定化させ、創傷治癒を促進させることができる。
The cell growth promoting agent of the present invention is excellent in cell growth promoting action. In addition, the cell growth promoter of the present invention can be applied to, for example, basic cosmetics, medicinal cosmetics, pharmaceutical preparations, and the like, and is highly safe with significantly improved cell growth promoting effects.
The TGF-β production promoter of the present invention can maintain cell homeostasis by controlling cell proliferation / differentiation by promoting TGF-β production.
The collagen gel contraction-promoting agent of the present invention promotes the contraction of the collagen gel, thereby promoting the fixation of the graft in the treatment of intractable skin diseases such as wound healing, skin ulcer and keloid, or skin transplantation. it can.
The integrin production promoter of the present invention can stabilize tissue structure and promote wound healing by promoting integrin production.
以下、本発明について詳述する。
本発明で用いるシカクマメ(Psophocarpus)属に属する植物は、マメ科の熱帯産つる性の草本である。本発明ではシカクマメ属に属する植物であれば特に限定されるものではなく、任意に用いることができる。本発明では中でも、シカクマメ(学名:Psophocarpus tetragonolobus)が好ましく用いられる。シカクマメは、翼マメ(ウイングドビーン)とも称されている。改良品種として「ウリズン」等が知られる。市販品としては、サカタのタネなどで購入できる。
シカクマメ抽出物は、従来より美白作用や保湿作用、ラミニン5産生促進作用を有する成分としては知られているが(特開2002−265343号公報、特開2002−265324号公報、特開2003−313135号公報参照)、細胞増殖促進作用を有することは知られておらず、本発明者が初めて見出したものである。
Hereinafter, the present invention will be described in detail.
The plant belonging to the genus Psophocarpus used in the present invention is a tropical vine of the leguminous family. In this invention, if it is a plant which belongs to the winged genus, it will not specifically limit, It can use arbitrarily. In the present invention, winged bean (scientific name: Psophocarpus tetragonolobus) is preferably used. The winged bean is also called a winged bean. “Urisun” is known as an improved variety. Commercially available products can be purchased from Sakata Seeds.
The winged bean extract is conventionally known as a component having a whitening action, a moisturizing action, and a laminin 5 production promoting action (JP 2002-265343 A, JP 2002-265324 A, JP 2003-313135 A). It is not known to have a cell growth promoting action, and was first discovered by the present inventor.
本発明に用いられるシカクマメ(Psophocarpus)属植物の抽出物は、シカクマメ(Psophocarpus)属植物の葉、茎、枝、花、樹皮、種子、果実、根茎または植物全草等を抽出溶媒と共に浸漬または加熱還流した後、濾過し濃縮して得られる。使用部位としては、植物体の任意の部位を用いることができるが、種子を用いるのが特に好ましい。 The extract of the plant belonging to the genus Psophocarpus used in the present invention is obtained by immersing or heating leaves, stems, branches, flowers, bark, seeds, fruits, rhizomes or whole plants of plants of the genus Psophocarpus with an extraction solvent. After refluxing, it is obtained by filtration and concentration. Although any part of the plant can be used as the part to be used, it is particularly preferable to use seeds.
シカクマメ(Psophocarpus)属植物の抽出物は、常法により得ることができ、例えばシカクマメ(Psophocarpus)属植物を抽出溶媒とともに浸漬または加熱還流した後、濾過し、濃縮して得ることができる。抽出溶媒としては、通常抽出に用いられる溶媒であれば任意に用いることができ、例えば、水、メタノール、エタノール、プロピレングリコール、1,3−ブチレングリコール、グリセリン等のアルコール類、含水アルコール類、クロロホルム、ジクロルエタン、四塩化炭素、アセトン、酢酸エチル、ヘキサン等の有機溶媒等を、それぞれ単独あるいは組み合わせて用いることができる。上記溶媒で抽出した得た抽出液をそのまま、あるいは濃縮したエキスを吸着法、例えばイオン交換樹脂を用いて不純物を除去したものや、ポーラスポリマー(例えばアンバーライトXAD−2)のカラムにて吸着させた後、メタノールまたはエタノールで溶出し、濃縮したものも使用することができる。また分配法、例えば水/酢酸エチルで抽出した抽出物等も用いられる。 An extract of a genus Psophocarpus can be obtained by a conventional method. For example, a genus Psophocarpus can be obtained by dipping or heating under reflux with an extraction solvent, followed by filtration and concentration. As the extraction solvent, any solvent that is usually used for extraction can be used. For example, water, methanol, ethanol, propylene glycol, 1,3-butylene glycol, glycerin and other alcohols, hydrous alcohols, chloroform , Organic solvents such as dichloroethane, carbon tetrachloride, acetone, ethyl acetate, hexane and the like can be used alone or in combination. The extract obtained by extraction with the above solvent is adsorbed as it is, or the concentrated extract is adsorbed by an adsorption method, for example, by removing impurities using an ion exchange resin, or by a column of a porous polymer (eg Amberlite XAD-2). Thereafter, a product eluted with methanol or ethanol and concentrated can also be used. Further, a partitioning method, for example, an extract extracted with water / ethyl acetate can be used.
こうして得られる抽出液は、そのまま、あるいはエタノール等でさらに希釈し、または固化後、乾燥物をそのまま、もしくは乾燥物を例えばエタノールに再溶解して、本発明で用いる調製物とすることができる。 The extract thus obtained can be used as it is, or further diluted with ethanol or the like, or solidified, and then the dried product can be used as it is, or the dried product can be redissolved in, for example, ethanol to obtain the preparation used in the present invention.
このようにして得たシカクマメ(Psophocarpus)属植物の抽出物は、優れた細胞増殖促進作用を有する。このようなシカクマメ(Psophocarpus)属植物の抽出物よりなる細胞増殖促進剤は、好ましくは外用剤や食品に配合して用いられる。 The extract of the genus Psophocarpus thus obtained has an excellent cell growth promoting action. Such a cell growth promoter composed of an extract of the plant of the genus Psophocarpus is preferably used in a preparation for external use or food.
また本発明の細胞増殖促進剤は、優れた細胞増殖促進能および細胞接着促進能を有することから、皮膚外用剤や食品以外に、例えば、培地添加剤としての利用が可能である。従来、培地添加剤としては、牛脳下垂体エキスや牛胎児血清などの動物由来原料を使用してきたが、シカクマメエキスを用いることで、非動物原料としての使用が可能となる。また、本発明の細胞増殖促進剤は、再生医療での利用も可能であり、人工皮膚、自家培養皮膚作製にも利用可能で、非動物原料のため、安全性面からも価値が高いものである。また、関節炎の予防治療や熱傷の初期治療等としての適用も可能である。 Moreover, since the cell growth promoting agent of the present invention has excellent cell growth promoting ability and cell adhesion promoting ability, it can be used as, for example, a medium additive in addition to a skin external preparation or food. Conventionally, as a culture medium additive, animal-derived materials such as bovine pituitary extract and fetal bovine serum have been used, but use of winged bean extract makes it possible to use it as a non-animal material. The cell growth promoter of the present invention can also be used in regenerative medicine, can be used for artificial skin and self-cultured skin preparation, and is a non-animal raw material, so it is highly valuable in terms of safety. is there. It can also be applied as an arthritis prevention treatment or an initial treatment for burns.
ここで細胞とは、特に限定されないが、哺乳動物細胞を挙げることができる。哺乳動物細胞とは、ヒト、サル、ウシ、ラットやマウス等の哺乳動物の組織・臓器細胞またはこれら由来の細胞であって、個体の細胞、個体から取り出した初代細胞、または培養細胞、遺伝子を導入した細胞のいずれでもよい。また細胞の種類も、特に限定されず、外胚葉由来(皮膚表皮、神経など)、内胚葉由来(消化管、臓器組織など)、中胚葉由来(皮膚の真皮、結合組織、心臓・血管、筋肉など)、神経冠由来(末梢神経など)のいずれでもよい。 Here, the cell is not particularly limited, and examples thereof include mammalian cells. Mammalian cells are tissue, organ cells or cells derived from mammals such as humans, monkeys, cows, rats, mice, etc., which are cells of individuals, primary cells removed from individuals, cultured cells, and genes. Any of the introduced cells may be used. The cell type is not particularly limited, and is derived from ectoderm (skin epidermis, nerve, etc.), endoderm (digestive tract, organ tissue, etc.), mesoderm (skin dermis, connective tissue, heart / blood vessel, muscle) Etc.) and neural crest-derived (peripheral nerve etc.).
投与方法としては、in vitro法またはex vivo法であれば、細胞を培養している培養液中に添加、あるいは細胞に直接添加すればよい。添加量は、細胞の種類、細胞数等により適宜調整することができるが、細胞毒性が認められず細胞増殖促進活性が認められればよい。 As an administration method, in the case of an in vitro method or an ex vivo method, it may be added to a culture medium in which cells are cultured or added directly to cells. The amount added can be appropriately adjusted depending on the type of cells, the number of cells, etc., but it is sufficient that no cell toxicity is observed and cell growth promoting activity is recognized.
本発明の細胞増殖促進剤類を皮膚外用剤に配合して用いる場合、皮膚外用剤全量中に乾燥重量として0.0001〜10質量%配合するのが好ましく、より好ましくは0.001〜1質量%である。0.0001質量%未満では本発明の細胞増殖促進作用が十分に発揮され難く、一方、10質量%超では製剤化が難しいので好ましくない。また、1質量%を超えて配合してもさほど大きな効果の向上は認められない。 When the cell growth promoter of the present invention is used by blending with a skin external preparation, it is preferably blended in a dry skin weight of 0.0001 to 10 mass%, more preferably 0.001 to 1 mass in the total amount of the skin external preparation. %. If it is less than 0.0001% by mass, the cell growth promoting action of the present invention is not sufficiently exerted. On the other hand, if it exceeds 10% by mass, it is difficult to make a preparation. Moreover, even if it exceeds 1 mass%, the improvement of the big effect is not recognized.
本発明の細胞増殖促進剤を皮膚外用剤に用いる場合、上記成分に加えて、さらに必要により、本発明の効果を損なわない範囲内で、通常化粧品や医薬品等の皮膚外用剤に用いられる成分、例えば保湿剤、酸化防止剤、油分、紫外線防御剤、界面活性剤、増粘剤、アルコール類、粉末成分、色材、水性成分、水、各種皮膚栄養剤等を必要に応じて適宜配合することができる。 When the cell growth promoter of the present invention is used for an external preparation for skin, in addition to the above components, components that are usually used for external preparations for skin such as cosmetics and pharmaceuticals, as long as they do not impair the effects of the present invention, For example, moisturizers, antioxidants, oils, UV protection agents, surfactants, thickeners, alcohols, powder components, color materials, aqueous components, water, various skin nutrients, etc., should be added as necessary. Can do.
さらに、エデト酸二ナトリウム、エデト酸三ナトリウム、クエン酸ナトリウム、ポリリン酸ナトリウム、メタリン酸ナトリウム、グルコン酸等の金属イオン封鎖剤、メチルパラベン、エチルパラベン、ブチルパラベン等の防腐剤、カフェイン、タンニン、ベラパミル、トラネキサム酸およびその誘導体、甘草抽出物、グラブリジン、カリンの果実の熱水抽出物、各種生薬、酢酸トコフェロール、グリチルリチン酸およびその誘導体またはその塩等の薬剤、ビタミンC、アスコルビン酸リン酸マグネシウム、アスコルビン酸グルコシド、アルブチン、コウジ酸等の美白剤、グルコース、フルクトース、マンノース、ショ糖、トレハロース等の糖類、レチノイン酸、レチノール、レチノール酢酸、レチノールパルミチン酸等のビタミンA誘導体類なども適宜配合することができる。 Furthermore, edetate disodium, edetate trisodium, sodium citrate, sodium polyphosphate, sodium metaphosphate, sequestering agents such as gluconic acid, preservatives such as methylparaben, ethylparaben, butylparaben, caffeine, tannin, Verapamil, tranexamic acid and its derivatives, licorice extract, grabrizine, hot water extract of karin fruit, various herbal medicines, tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, Whitening agents such as ascorbic acid glucoside, arbutin, kojic acid, sugars such as glucose, fructose, mannose, sucrose, trehalose, vitamin A derivatives such as retinoic acid, retinol, retinol acetic acid, retinol palmitic acid It may be blended Domo.
また、本発明の細胞増殖促進剤を含む皮膚外用剤は、外皮に適用される化粧料、医薬部外品等、特に好適には化粧料に広く適用することが可能であり、その剤型も、皮膚に適用できるものであればいずれでもよく、溶液系、可溶化系、乳化系、粉末分散系、水−油二層系、水−油−粉末三層系、軟膏、化粧水、ゲル、エアゾール等、任意の剤型が適用される。 Further, the external preparation for skin containing the cell growth promoter of the present invention can be widely applied to cosmetics, quasi-drugs and the like, particularly preferably cosmetics applied to the outer skin, and the dosage form is also Any one can be used as long as it is applicable to the skin, solution system, solubilization system, emulsification system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, ointment, lotion, gel, Any dosage form such as aerosol is applied.
また、本発明の細胞増殖促進剤を含む皮膚外用剤の使用形態も任意であり、例えば化粧水、乳液、クリーム、パック等のフェーシャル化粧料、サンスクリーン、マッサージオイル等のボディ用化粧料やファンデーション、口紅、アイシャドウ等のメーキャップ化粧料、毛髪用化粧料、芳香化粧料、浴用剤等に用いることができる。 The use form of the external preparation for skin containing the cell growth promoter of the present invention is also arbitrary, for example, facial cosmetics such as lotion, milky lotion, cream and pack, cosmetics for body such as sunscreen and massage oil, and foundations. It can be used in makeup cosmetics such as lipsticks and eye shadows, hair cosmetics, aromatic cosmetics, bath preparations and the like.
シカクマメ属植物抽出物を食品や医薬品製剤に配合して用いる場合、上記成分に加えて、さらに必要により、本発明の効果を損なわない範囲内で、例えば、顆粒状、粒状、ペースト状、ゲル状、固形状、または、液体状に任意に成形することができる。これらには、飲食品等に含有することが認められている公知の各種物質、例えば、結合剤、崩壊剤、増粘剤、分散剤、再吸収促進剤、矯味剤、緩衝剤、界面活性剤、溶解補助剤、保存剤、乳化剤、等張化剤、安定化剤やpH調製剤などの賦形剤など適宜配合することができる。
剤型も任意で、例えば錠剤、顆粒剤、散剤、カプセル剤等適宜調整できる。
When the winged genus plant extract is used in a food or pharmaceutical preparation, in addition to the above components, if necessary, within the range not impairing the effects of the present invention, for example, granular, granular, pasty, gel-like It can be arbitrarily molded into a solid or liquid form. These include various known substances that are recognized to be contained in foods and drinks, such as binders, disintegrants, thickeners, dispersants, reabsorption accelerators, flavoring agents, buffers, and surfactants. , Solubilizers, preservatives, emulsifiers, isotonic agents, excipients such as stabilizers and pH adjusters, and the like can be appropriately blended.
The dosage form is also arbitrary and can be appropriately adjusted, for example, tablets, granules, powders, capsules and the like.
なお、上記の剤型および使用形態に本発明の細胞増殖促進剤を含む皮膚外用剤、食品、医薬製剤が採り得る形態が限定されるものではない。 In addition, the form which the skin external preparation containing the cell growth promoter of this invention, a foodstuff, and a pharmaceutical formulation can take in said dosage form and usage form is not limited.
次に、実施例を挙げて本発明をさらに詳細に説明するが、本発明の技術的範囲はこれによってなんら限定されるものでない。 EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, the technical scope of this invention is not limited at all by this.
1.試料(植物抽出物)の調製
シカクマメの種子部分50gを、室温で1週間90%エタノールに浸漬し、抽出液を濃縮し、90%エタノール抽出物(乾燥物)2.9gを得た。得られたシカクマメ抽出物を用いて、以下の実験を行った。
1. Preparation of sample (plant extract) 50 g of winged bean seeds were immersed in 90% ethanol for 1 week at room temperature, and the extract was concentrated to obtain 2.9 g of 90% ethanol extract (dry product). The following experiment was performed using the obtained winged bean extract.
2.線維芽細胞増殖促進作用の測定
96穴プレートに、10%FBSを含むDMEMを用いてヒト皮膚線維芽細胞を5千個播種し、接着後FBSを0.5%含む培地に置換した。翌日DMSOに溶解したシカクマメ抽出物を10-4〜10-2質量%添加した(DMSO終濃度0.5%)。さらに72時間培養後培地を採取した。プレートにヘキスト33342(ヘキスト社製)溶液を入れてDNA染色を行った後、蛍光度を測定し、薬剤無添加(コントロール)群との比から細胞増殖率を求めた。結果を表1に示す。
ただし、本実施例において細胞の種類はいずれのものでも同様の結果が得られた。
2. Measurement of Fibroblast Growth Promoting Activity A 96-well plate was seeded with 5,000 human skin fibroblasts using DMEM containing 10% FBS, and after adhesion, the medium was replaced with a medium containing 0.5% FBS. The next day, winged bean extract dissolved in DMSO was added at 10 −4 to 10 −2 mass% (DMSO final concentration 0.5%). After further cultivation for 72 hours, the medium was collected. A Hoechst 33342 (Hoechst) solution was added to the plate and subjected to DNA staining. Then, the fluorescence was measured, and the cell proliferation rate was determined from the ratio to the drug-free (control) group. The results are shown in Table 1.
However, the same result was obtained for any cell type in this example.
表1よりシカクマメ抽出物は、線維芽細胞に対して優れた増殖促進効果を有することがわかった。 From Table 1, it was found that winged bean extract has an excellent growth promoting effect on fibroblasts.
3.TGF−β1産生促進作用の測定
10cmシャーレにHaCaT細胞を播種し、KGM培地(クラボウ製)でシャーレ全体の7割程度に増えるまで培養した。0.1%BSA含有KBM培地に置換し同時にDMSOに溶解したシカクマメ抽出物を0.0002質量%,0.001質量%,及び0.005質量%添加(DMSO終濃度0.5%)してさらに48時間培養を行った。
培養後、培地を採取し、TGF−β1測定キット(r&d systems社製)を用いてTGF−β1量を測定した。またシャーレ中のDNA量を測定し、細胞数の指標とした。DNA量の測定はヘキスト33258(ヘキスト社製)を用いた蛍光測定法で行った。なお、上記実験濃度では細胞毒性は認められなかった。抽出物無添加群(コントロール)のDNAあたりのTGF−β1量を100とした時の、シカクマメ抽出物添加群の値をTGF−β1産生促進率(%)とした。結果を表2に示す。
3. Measurement of TGF-β1 production promoting action HaCaT cells were seeded in a 10 cm petri dish and cultured in a KGM medium (manufactured by Kurabo Industries Inc.) until it increased to about 70% of the whole petri dish. Add 0.0002 wt%, 0.001 wt%, and 0.005 wt% winged bean extract that was replaced with 0.1% BSA-containing KBM medium and simultaneously dissolved in DMSO (DMSO final concentration 0.5%) The culture was further performed for 48 hours.
After the culture, the medium was collected, and the amount of TGF-β1 was measured using a TGF-β1 measurement kit (manufactured by r & d systems). Further, the amount of DNA in the petri dish was measured and used as an index of the number of cells. The amount of DNA was measured by a fluorescence measurement method using Hoechst 33258 (manufactured by Hoechst). Note that no cytotoxicity was observed at the above experimental concentrations. When the amount of TGF-β1 per DNA in the extract-free group (control) was taken as 100, the value of the winged bean extract-added group was defined as the TGF-β1 production promotion rate (%). The results are shown in Table 2.
表2から明らかなように、シカクマメ抽出液は、優れたTGF−β1産生促進効果を有することがわかった。 As apparent from Table 2, the winged bean extract was found to have an excellent TGF-β1 production promoting effect.
4.コラーゲンゲル収縮能評価試験(ヒト皮膚線維芽細胞によるI型コラーゲンゲル収縮能に対する作用の評価)
線維芽細胞(5x104 cell/ml)懸濁コラーゲン溶液(高研株式会社製 I型コラーゲンを使用)を氷上にて調製後、37℃でコラーゲンをゲル化した。その後、被験物質(コントロールとしてDMSO、または精製水)及び0.25%FBS含有DMEM培地を添加し、シャーレ壁面からゲルを剥離し、コラーゲン収縮を行った。1,2,3,6日後、コラーゲンゲルの直径を三方向から測定し平均値を求めた。収縮前の直径を収縮率0%とし、被験物質添加後の収縮率を求めた(各群n=3)。結果を表3に示す。
4). Collagen gel contractility evaluation test (Evaluation of the effect of human skin fibroblasts on type I collagen gel contractility)
After a fibroblast (5 × 10 4 cell / ml) suspension collagen solution (type I collagen manufactured by Koken Co., Ltd.) was prepared on ice, the collagen was gelled at 37 ° C. Thereafter, a test substance (DMSO or purified water as a control) and 0.25% FBS-containing DMEM medium were added, the gel was peeled from the petri dish wall surface, and collagen contraction was performed. After 1, 2, 3 and 6 days, the diameter of the collagen gel was measured from three directions and the average value was determined. The diameter before shrinkage was taken as 0% shrinkage, and the shrinkage after adding the test substance was determined (each group n = 3). The results are shown in Table 3.
表3から明らかなように、シカクマメエキスは、優れたコラーゲンゲル収縮促進効果を有することがわかった。 As is apparent from Table 3, the winged bean extract was found to have an excellent collagen gel contraction promoting effect.
5.真皮線維芽細胞におけるインテグリン産生促進能評価試験
ヒト皮膚線維芽細胞にシカクマメエキスを作用させ、24時間後にトリプシン/EDTAにより細胞を剥離し、血清(FBS)含有培地で中和後、細胞を0.01%FCS、0.02%NaN3含有PBSにて洗浄し細胞を回収した。一次抗体として抗ヒトインテグリンα2、α2β1、β1をそれぞれ100倍希釈で、二次抗体としてFITCラベル抗マウスIgG1を100倍希釈で用いた。ブランクは一次抗体にマウスIgG1を用いた。細胞表面のインテグリン量を、フローサイトメーターを用いて測定した。結果を表4に示す。
5). Evaluation test of integrin production promoting ability in dermis fibroblasts A winged bean extract was allowed to act on human dermal fibroblasts, 24 hours later, the cells were detached with trypsin / EDTA, neutralized with a serum (FBS) -containing medium, The cells were recovered by washing with PBS containing 01% FCS and 0.02% NaN 3 . Anti-human integrin α2 as the primary antibody, [alpha] 2 [beta] 1, .beta.1 at 100-fold dilution, respectively, using a FITC-labeled anti-mouse IgG 1 in 100 dilution as a secondary antibody. The blank used mouse IgG1 as the primary antibody. The amount of integrin on the cell surface was measured using a flow cytometer. The results are shown in Table 4.
6.表皮細胞におけるインテグリン産生促進能評価試験
HaCaT細胞にシカクマメエキスを作用させ、24時間後にトリプシン/EDTAにより細胞を剥離し、FCSで中和後、細胞を0.01%FCS、0.02%NaN3含有PBSにて洗浄し細胞を回収した。一次抗体として抗ヒトインテグリンα2、α3、α2β1、β1をそれぞれ100倍希釈で、二次抗体としてFITCラベル抗マウスIgG1を100倍希釈で用いた。ブランクは一次抗体にマウスIgG1を用いた。細胞表面のインテグリン量を、フローサイトメーターを用いて測定した。結果を表5に示す。
6). Evaluation test of integrin production promoting ability in epidermal cells After the action of winged bean extract on HaCaT cells, the cells were detached with trypsin / EDTA 24 hours later, neutralized with FCS, and then the cells were 0.01% FCS, 0.02% NaN 3. The cells were collected by washing with PBS containing. Anti-human integrin α2 as the primary antibody, .alpha.3, [alpha] 2 [beta] 1, .beta.1 at 100-fold dilution, respectively, using a FITC-labeled anti-mouse IgG 1 in 100 dilution as a secondary antibody. The blank used mouse IgG1 as the primary antibody. The amount of integrin on the cell surface was measured using a flow cytometer. The results are shown in Table 5.
以上のように、シカクマメエキスは、線維芽細胞および表皮細胞両方のインテグリン産生を高めることが明らかとなった。 As described above, it was revealed that winged bean extract enhances integrin production in both fibroblasts and epidermal cells.
次に、本発明の細胞増殖促進剤類を含む皮膚外用剤の処方例を示す。 Next, the formulation example of the skin external preparation containing the cell growth promoter of this invention is shown.
配合処方例1 クリーム
(配合成分) (質量%)
(1)ステアリン酸 2.0
(2)ステアリルアルコール 7.0
(3)水添ラノリン 2.0
(4)スクワラン 5.0
(5)2−オクチルドデシルアルコール 6.0
(6)ポリオキシエチレン(25モル)
セチルアルコールエーテル 3.0
(7)グリセリンモノステアリン酸エステル 2.0
(8)プロピレングリコール 5.0
(9)細胞増殖促進剤(シカクマメ50%エタノール抽出物)(乾燥換算)
0.05
(10)亜硫酸水素ナトリウム 0.03
(11)エチルパラベン 0.3
(12)香料 適量
(13)精製水 残余
(製法)
(13)に(8)を加え溶解し、加熱して70℃に保った(水相)。一方、(1)〜(7)、(9)〜(12)を混合して加熱溶融し、70℃に保った(油相)。次いで、水相に油相を加え予備乳化を行い、ホモミキサーで均一に乳化した後、よく攪拌しながら30℃まで冷却した。
Formulation Example 1 Cream (Compounding ingredients) (mass%)
(1) Stearic acid 2.0
(2) Stearyl alcohol 7.0
(3) Hydrogenated lanolin 2.0
(4) Squalane 5.0
(5) 2-Octyldodecyl alcohol 6.0
(6) Polyoxyethylene (25 mol)
Cetyl alcohol ether 3.0
(7) Glycerin monostearate ester 2.0
(8) Propylene glycol 5.0
(9) Cell growth promoter (winged bean 50% ethanol extract) (dry conversion)
0.05
(10) Sodium bisulfite 0.03
(11) Ethylparaben 0.3
(12) Perfume appropriate amount (13) Purified water Residue (Production method)
(8) was added to (13) and dissolved, and heated to 70 ° C. (water phase). On the other hand, (1) to (7) and (9) to (12) were mixed, heated and melted, and kept at 70 ° C. (oil phase). Subsequently, the oil phase was added to the aqueous phase, preliminarily emulsified, and uniformly emulsified with a homomixer, and then cooled to 30 ° C. with good stirring.
配合処方例2 クリーム
(配合成分) (質量%)
(1)固形パラフィン 5.0
(2)ミツロウ 10.0
(3)ワセリン 15.0
(4)グリセリンモノステアリン酸エステル 2.0
(5)ポリオキシエチレン(20モル)
ソルビタンモノラウリン酸エステル 3.0
(6)石けん粉末 0.1
(7)硼砂 0.2
(8)TGF−β産生促進剤(シカクマメ70%1,3−ブチレングリコール抽出物)(乾燥換算) 0.05
(9)亜硫酸水素ナトリウム 0.03
(10)エチルパラベン 0.3
(11)香料 適量
(12)精製水 残余
(製法)
(12)に(6)〜(7)を加え、加熱溶解して70℃に保った(水相)。一方、(1)〜(5)、(8)〜(11)を混合し加熱溶融し、70℃に保った(油相)。次いで、水相に油相を攪拌しながら徐々に加え反応を行った。反応終了後、ホモミキサーで均一に乳化した後、よく攪拌しながら30℃まで冷却した。
Formulation Example 2 Cream (Compounding ingredients) (mass%)
(1) Solid paraffin 5.0
(2) Beeswax 10.0
(3) Vaseline 15.0
(4) Glycerin monostearate ester 2.0
(5) Polyoxyethylene (20 mol)
Sorbitan monolaurate 3.0
(6) Soap powder 0.1
(7) Borax 0.2
(8) TGF-β production promoter (winged bean 70% 1,3-butylene glycol extract) (dry conversion) 0.05
(9) Sodium bisulfite 0.03
(10) Ethylparaben 0.3
(11) Perfume appropriate amount (12) Purified water Residue (Production method)
(6) to (7) were added to (12), dissolved by heating and kept at 70 ° C. (aqueous phase). On the other hand, (1) to (5) and (8) to (11) were mixed, heated and melted, and kept at 70 ° C. (oil phase). Next, the oil phase was gradually added to the aqueous phase while stirring to carry out the reaction. After completion of the reaction, the mixture was uniformly emulsified with a homomixer and then cooled to 30 ° C. with good stirring.
配合処方例3 乳液
(配合成分) (質量%)
(1)ステアリン酸 2.5
(2)セチルアルコール 1.5
(3)ワセリン 5.0
(4)流動パラフィン 10.0
(5)ポリオキシエチレン(10モル)
モノオレイン酸エステル 3.0
(6)ポリエチレングリコール1500 3.0
(7)トリエタノールアミン 1.0
(8)カルボキシビニルポリマー 0.05
(「カーボポール941」;B.F.Goodrich Chemical Company)
(9)コラーゲンゲル収縮促進剤(シカクマメ水抽出物)(乾燥換算)
0.0001
(10)亜硫酸水素ナトリウム 0.01
(11)エチルパラベン 0.01
(12)香料 適量
(13)精製水 残余
(製法)
少量の(13)に(8)を溶解した(A相)。残りの(13)に(6)〜(7)を加え、加熱溶解して70℃に保った(水相)。一方、(1)〜(5)、(9)〜(12)を混合し加熱溶融して70℃に保った(油相)。水相に油相を加え予備乳化を行い、さらにA相を加えホモミキサーで均一に乳化し、乳化後よく攪拌しながら30℃まで冷却した。
Formulation Example 3 Emulsion (Compounding ingredients) (mass%)
(1) Stearic acid 2.5
(2) Cetyl alcohol 1.5
(3) Vaseline 5.0
(4) Liquid paraffin 10.0
(5) Polyoxyethylene (10 mol)
Monooleate 3.0
(6) Polyethylene glycol 1500 3.0
(7) Triethanolamine 1.0
(8) Carboxyvinyl polymer 0.05
(“Carbopol 941”; BFGoodrich Chemical Company)
(9) Collagen gel shrinkage promoter (winged bean water extract) (dry conversion)
0.0001
(10) Sodium bisulfite 0.01
(11) Ethylparaben 0.01
(12) Perfume appropriate amount (13) Purified water Residue (Production method)
(8) was dissolved in a small amount of (13) (A phase). (6) to (7) were added to the remaining (13), dissolved by heating and kept at 70 ° C. (aqueous phase). On the other hand, (1) to (5) and (9) to (12) were mixed, heated and melted, and kept at 70 ° C. (oil phase). The oil phase was added to the aqueous phase for preliminary emulsification, and the A phase was further added and uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. with good stirring.
配合処方例4 乳液
(配合成分) (質量%)
(1)マイクロクリスタリンワックス 1.0
(2)ミツロウ 2.0
(3)ラノリン 20.0
(4)流動パラフィン 10.0
(5)スクワラン 5.0
(6)ソルビタンセスキオレイン酸エステル 4.0
(7)ポリオキシエチレン(20モル)
ソルビタンモノオレイン酸エステル 1.0
(8)プロピレングリコール 7.0
(9)インテグリン産生促進剤(シカクマメ50%1,3−ブチレングリコール抽出物)(乾燥換算) 10.0
(10)亜硫酸水素ナトリウム 0.01
(11)エチルパラベン 0.3
(12)香料 適量
(13)精製水 残余
(製法)
(13)に(8)を加え、加熱して70℃に保った(水相)。一方、(1)〜(7)、(9)〜(12)を混合し、加熱溶融して70℃に保った(油相)。油相を攪拌しながら水相を徐々に加え、ホモミキサーで均一に乳化し、乳化後よく攪拌しながら30℃まで冷却した。
Formulation Example 4 Emulsion (Compounding ingredient) (mass%)
(1) Microcrystalline wax 1.0
(2) Beeswax 2.0
(3) Lanolin 20.0
(4) Liquid paraffin 10.0
(5) Squalane 5.0
(6) Sorbitan sesquioleate ester 4.0
(7) Polyoxyethylene (20 mol)
Sorbitan monooleate 1.0
(8) Propylene glycol 7.0
(9) Integrin production promoter (winged bean 50% 1,3-butylene glycol extract) (dry conversion) 10.0
(10) Sodium bisulfite 0.01
(11) Ethylparaben 0.3
(12) Perfume appropriate amount (13) Purified water Residue (Production method)
(8) was added to (13) and heated to 70 ° C. (aqueous phase). On the other hand, (1) to (7) and (9) to (12) were mixed, melted by heating and kept at 70 ° C. (oil phase). The aqueous phase was gradually added while stirring the oil phase, and the mixture was uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. with good stirring.
配合処方例5 ゼリー
(配合成分) (質量%)
(1)95%エチルアルコール 10.0
(2)ジプロピレリングリコール 15.0
(3)ポリオキシエチレン(50モル)
オレイルアルコールエーテル 2.0
(4)カルボキシビニルポリマー 1.0
(「カーボポール941」;B.F.Goodrich Chemical Company)
(5)苛性ソーダ 0.15
(6)L−アルギニン 0.1
(7)細胞増殖促進剤(シカクマメ90%1,3−ブチレングリコール抽出物)(乾燥換算) 7.0
(8)2−ヒドロキシ−4−メトキシ
ベンゾフェノンスルホン酸ナトリウム 0.05
(9)エチレンジアミンテトラアセテート・
3ナトリウム・2水和物 0.05
(10)メチルパラベン 0.2
(11)香料 適量
(12)精製水 残余
(製法)
(12)に(4)を均一に溶解した(水相)。一方、(1)に(7)と(3)を溶解し、これを水相に添加した。次いでここに、(2)、(8)〜(11)を加えた後、(5)、(6)で中和させ増粘した。
Formulation Example 5 Jelly (Compounding ingredients) (mass%)
(1) 95% ethyl alcohol 10.0
(2) Dipropylene glycol 15.0
(3) Polyoxyethylene (50 mol)
Oleyl alcohol ether 2.0
(4) Carboxyvinyl polymer 1.0
(“Carbopol 941”; BFGoodrich Chemical Company)
(5) Caustic soda 0.15
(6) L-arginine 0.1
(7) Cell growth promoter (winged bean 90% 1,3-butylene glycol extract) (dry conversion) 7.0
(8) 2-hydroxy-4-methoxy
Sodium benzophenone sulfonate 0.05
(9) Ethylenediaminetetraacetate
Trisodium dihydrate 0.05
(10) Methylparaben 0.2
(11) Perfume appropriate amount (12) Purified water Residue (Production method)
(4) was uniformly dissolved in (12) (aqueous phase). On the other hand, (7) and (3) were dissolved in (1) and added to the aqueous phase. Next, (2) and (8) to (11) were added thereto, and then neutralized and thickened with (5) and (6).
配合処方例6 美容液
(配合成分) (質量%)
(A相)
(1)95%エチルアルコール 10.0
(2)ポリオキシエチレン(20モル)オクチルドデカノール 1.0
(3)パントテニルエチルエーテル 0.1
(4)TGF−β産生促進剤(シカクマメ90%エタノール抽出物)(乾燥換算)
1.5
(5)メチルパラベン 0.15
(B相)
(6)水酸化カリウム 0.1
(C相)
(7)グリセリン 5.0
(8)ジプロピレリングリコール 10.0
(9)亜硫酸水素ナトリウム 0.03
(10)カルボキシビニルポリマー 0.2
(「カーボポール941」;B.F.Goodrich Chemical Company)
(11)精製水 残余
(製法)
A相、C相をそれぞれ均一に溶解し、C相にA相を加えて可溶化した。次いでB相を加え充填を行った。
Formulation Example 6 Beauty Liquid (Compounding ingredients) (mass%)
(Phase A)
(1) 95% ethyl alcohol 10.0
(2) Polyoxyethylene (20 mol) octyldodecanol 1.0
(3) Pantothenyl ethyl ether 0.1
(4) TGF-β production promoter (winged bean 90% ethanol extract) (dry conversion)
1.5
(5) Methylparaben 0.15
(Phase B)
(6) Potassium hydroxide 0.1
(Phase C)
(7) Glycerin 5.0
(8) Dipropylene glycol 10.0
(9) Sodium bisulfite 0.03
(10) Carboxyvinyl polymer 0.2
(“Carbopol 941”; BFGoodrich Chemical Company)
(11) Purified water residue (production method)
The A phase and the C phase were uniformly dissolved, and the A phase was added to the C phase and solubilized. Then phase B was added and filled.
配合処方例7 パック
(配合成分) (質量%)
(A相)
(1)ジプロピレングリコール 5.0
(2)ポリオキシエチレン(60モル)硬化ヒマシ油 5.0
(B相)
(3)コラーゲンゲル収縮促進剤(シカクマメ90%エタノール抽出物)(乾燥換算)
0.01
(4)オリーブ油 5.0
(5)酢酸トコフェロール 0.2
(6)エチルパラベン 0.2
(7)香料 0.2
(C相)
(8)亜硫酸水素ナトリウム 0.03
(9)ポリビニルアルコール(ケン化度90、重合度2000) 13.0
(10)エタノール 7.0
(11)精製水 残余
(製法)
A相、B相、C相をそれぞれ均一に溶解し、A相にB相を加えて可溶化した。次いでC相を加え充填を行った。
Formulation Example 7 Pack (mixing component) (mass%)
(Phase A)
(1) Dipropylene glycol 5.0
(2) Polyoxyethylene (60 mol) hydrogenated castor oil 5.0
(Phase B)
(3) Collagen gel contraction promoter (winged bean 90% ethanol extract) (dry conversion)
0.01
(4) Olive oil 5.0
(5) Tocopherol acetate 0.2
(6) Ethylparaben 0.2
(7) Fragrance 0.2
(Phase C)
(8) Sodium bisulfite 0.03
(9) Polyvinyl alcohol (degree of saponification 90, degree of polymerization 2000) 13.0
(10) Ethanol 7.0
(11) Purified water residue (production method)
A phase, B phase, and C phase were uniformly dissolved, and B phase was added to A phase to solubilize. C phase was then added and filled.
配合処方例8 固形ファンデーション
(配合成分) (質量%)
(1)タルク 43.1
(2)カオリン 15.0
(3)セリサイト 10.0
(4)亜鉛華 7.0
(5)二酸化チタン 3.8
(6)黄色酸化鉄 2.9
(7)黒色酸化鉄 0.2
(8)スクワラン 8.0
(9)イソステアリン酸 4.0
(10)モノオレイン酸POEソルビタン 3.0
(11)オクタン酸イソセチル 2.0
(12)インテグリン産生促進剤(シカクマメ50%エタノール抽出物)(乾燥換算)
1.0
(13)防腐剤 適量
(14)香料 適量
(製法)
(1)〜(7)の粉末成分をブレンダーで十分混合し、これに(8)〜(11)の油性成分、(12)、(13)、(14)を加え、よく混練した後、容器に充填、成型した。
Formulation Example 8 Solid Foundation (Composition Component) (mass%)
(1) Talc 43.1
(2) Kaolin 15.0
(3) Sericite 10.0
(4) Zinc flower 7.0
(5) Titanium dioxide 3.8
(6) Yellow iron oxide 2.9
(7) Black iron oxide 0.2
(8) Squalane 8.0
(9) Isostearic acid 4.0
(10) POE sorbitan monooleate 3.0
(11) Isocetyl octanoate 2.0
(12) Integrin production promoter (winged bean 50% ethanol extract) (dry conversion)
1.0
(13) Preservative appropriate amount (14) Fragrance appropriate amount (production method)
(1)-(7) powder components are sufficiently mixed with a blender, (8)-(11) oily components, (12), (13), (14) are added to this and kneaded well. Filled and molded.
配合処方例9 乳化ファンデーション(クリームタイプ)
(配合成分) (質量%)
(粉体部)
(1)二酸化チタン 10.3
(2)セリタイト 5.4
(3)カオリン 3.0
(4)黄色酸化鉄 0.8
(5)ベンガラ 0.3
(6)黒色酸化鉄 0.2
(油相)
(7)デカメチルシクロペンタシロキサン 11.5
(8)流動パラフィン 4.5
(9)ポリオキシエチレン変性ジメチルポリシロキサン 4.0
(水相)
(10)精製水 50.0
(11)1,3−ブチレングリコール 4.5
(12)細胞増殖促進剤(シカクマメ30%1,3−ブチレングリコール抽出物)(乾燥換算) 0.001
(13)防腐剤 適量
(14)香料 適量
(製法)
水相を加熱攪拌後、十分に混合粉砕した粉体部を添加してホモミキサー処理した。さらに加熱混合した油相を加えてホモミキサー処理した後、攪拌しながら香料を添加して室温まで冷却した。
Formulation Example 9 Emulsification Foundation (Cream Type)
(Compounding ingredients) (mass%)
(Powder part)
(1) Titanium dioxide 10.3
(2) Celiteite 5.4
(3) Kaolin 3.0
(4) Yellow iron oxide 0.8
(5) Bengala 0.3
(6) Black iron oxide 0.2
(Oil phase)
(7) Decamethylcyclopentasiloxane 11.5
(8) Liquid paraffin 4.5
(9) Polyoxyethylene-modified dimethylpolysiloxane 4.0
(Water phase)
(10) Purified water 50.0
(11) 1,3-butylene glycol 4.5
(12) Cell growth promoter (winged bean 30% 1,3-butylene glycol extract) (dry conversion) 0.001
(13) Preservative appropriate amount (14) Fragrance appropriate amount (production method)
After the aqueous phase was heated and stirred, the powder part sufficiently mixed and ground was added and homomixed. Furthermore, after adding the heat-mixed oil phase and carrying out a homomixer process, the fragrance | flavor was added while stirring and it cooled to room temperature.
配合処方例10 クッキー
(配合成分) (質量%)
薄力粉 45.0
バター 17.5
グラニュー糖 20.0
TGF−β産生促進剤(シカクマメ抽出物)(乾燥物) 4.0
ニンジンエキス 適量
卵 12.5
レモンフレーバー 1.0
(製法)
バターを撹拌しながら、グラニュー糖を徐々に添加した後、卵、シカクマメエキス、ニンジンエキスおよび香料を添加し、さらに撹拌した。十分に撹拌した後、均一に振るった薄力粉を加え、低速にて撹拌し、塊状で冷蔵庫にて寝かせた。その後、成型し、170℃、15分間焼成しクッキーとした。
Formulation Example 10 Cookie (Compounding ingredients) (mass%)
Soft flour 45.0
Butter 17.5
Granulated sugar 20.0
TGF-β production promoter (winged bean extract) (dried product) 4.0
Carrot extract appropriate amount Egg 12.5
Lemon flavor 1.0
(Manufacturing method)
While stirring butter, granulated sugar was gradually added, and then egg, winged bean extract, carrot extract and flavor were added and further stirred. After sufficiently stirring, a weakly shaken flour was added, stirred at low speed, and agglomerated and laid in a refrigerator. Then, it shape | molded and baked at 170 degreeC for 15 minutes, and was set as the cookie.
配合処方例11 軟膏
(配合成分) (質量%)
コラーゲンゲル収縮促進剤(シカクマメ抽出物) 2.0
ヨモギエキス 1.0
ステアリルアルコール 18.0
モクロウ 20.0
ポリオキシエチレン(20)モノオレイン酸エステル 0.25
グリセリンモノステアリン酸エステル 0.3
ワセリン 40.0
精製水 残余
(製法)
精製水にシカクマメエキスを加えて溶解し、70℃に保つ(水相)。残りの成分を70℃にて混合溶解する(油相)。水相に油相を加え、ホモミキサーで均一に乳化後、冷却して軟膏を得た。
Formulation Example 11 Ointment (Compounding ingredients) (mass%)
Collagen gel contraction promoter (winged bean extract) 2.0
Artemisia extract 1.0
Stearyl alcohol 18.0
Owl 20.0
Polyoxyethylene (20) monooleate 0.25
Glycerin monostearate 0.3
Vaseline 40.0
Purified water residue (production method)
The winged bean extract is added to purified water and dissolved, and kept at 70 ° C. (aqueous phase). The remaining components are mixed and dissolved at 70 ° C. (oil phase). An oil phase was added to the aqueous phase, and the mixture was uniformly emulsified with a homomixer and then cooled to obtain an ointment.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008190516A JP2010024211A (en) | 2008-07-24 | 2008-07-24 | Cell proliferation promoting agent |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008190516A JP2010024211A (en) | 2008-07-24 | 2008-07-24 | Cell proliferation promoting agent |
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| JP2010024211A true JP2010024211A (en) | 2010-02-04 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4764518B1 (en) * | 2010-07-28 | 2011-09-07 | 株式会社 資生堂 | Oral pore improver |
| JP4787908B1 (en) * | 2010-07-28 | 2011-10-05 | 株式会社 資生堂 | Oral menopausal symptoms |
| WO2012133223A1 (en) * | 2011-03-30 | 2012-10-04 | 株式会社資生堂 | Matrix metalloprotease (mmp) production inhibitor for oral use |
| JP2012206996A (en) * | 2011-03-30 | 2012-10-25 | Shiseido Co Ltd | Translocator protein (tspo) gene expression inhibitor for oral use |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003313135A (en) * | 2001-08-21 | 2003-11-06 | Shiseido Co Ltd | Skin care preparation |
| WO2005011717A1 (en) * | 2003-07-03 | 2005-02-10 | Greenpharma S.A. | Use of betulinic acid or an assayed plant extract in betulinic acid individually or associated for cosmetic, neutraceutical, veterinary and pharmaceutical use |
| KR20050111667A (en) * | 2004-05-21 | 2005-11-28 | 주식회사 엠디바이오알파 | Soybean extract of enhancing biosynthesis of hyaluronic acid and glycosaminoglycan |
-
2008
- 2008-07-24 JP JP2008190516A patent/JP2010024211A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003313135A (en) * | 2001-08-21 | 2003-11-06 | Shiseido Co Ltd | Skin care preparation |
| WO2005011717A1 (en) * | 2003-07-03 | 2005-02-10 | Greenpharma S.A. | Use of betulinic acid or an assayed plant extract in betulinic acid individually or associated for cosmetic, neutraceutical, veterinary and pharmaceutical use |
| KR20050111667A (en) * | 2004-05-21 | 2005-11-28 | 주식회사 엠디바이오알파 | Soybean extract of enhancing biosynthesis of hyaluronic acid and glycosaminoglycan |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4764518B1 (en) * | 2010-07-28 | 2011-09-07 | 株式会社 資生堂 | Oral pore improver |
| JP4787908B1 (en) * | 2010-07-28 | 2011-10-05 | 株式会社 資生堂 | Oral menopausal symptoms |
| WO2012014417A1 (en) * | 2010-07-28 | 2012-02-02 | 株式会社 資生堂 | Use of plant or like for improving pores, method for improving pores and oral preparation for improving pores |
| WO2012133223A1 (en) * | 2011-03-30 | 2012-10-04 | 株式会社資生堂 | Matrix metalloprotease (mmp) production inhibitor for oral use |
| JP2012206996A (en) * | 2011-03-30 | 2012-10-25 | Shiseido Co Ltd | Translocator protein (tspo) gene expression inhibitor for oral use |
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