WO2006101119A1 - Collagen synthesis promoter - Google Patents

Collagen synthesis promoter Download PDF

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Publication number
WO2006101119A1
WO2006101119A1 PCT/JP2006/305693 JP2006305693W WO2006101119A1 WO 2006101119 A1 WO2006101119 A1 WO 2006101119A1 JP 2006305693 W JP2006305693 W JP 2006305693W WO 2006101119 A1 WO2006101119 A1 WO 2006101119A1
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WIPO (PCT)
Prior art keywords
acid
collagen synthesis
skin
synthesis promoter
extract
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PCT/JP2006/305693
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French (fr)
Japanese (ja)
Inventor
Masami Tachikawa
Fumito Karakida
Zenji Kawakami
Daisuke Matsuura
Hirotoshi Kanatani
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Tsumura & Co.
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Publication of WO2006101119A1 publication Critical patent/WO2006101119A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations

Definitions

  • the present invention relates to a collagen synthesis promoter, and more specifically, a collagen synthesis promoter aimed at promoting collagen synthesis in fibroblasts, imparting freshness and firmness to the skin, and maintaining the water retaining ability of the epidermis. About.
  • Collagen is the main protein that forms the binding thread and weave of animals. Collagen occupies nearly 30% of the total protein of the human body. In the skin, collagen has a function of imparting freshness, thickness and thickness to the skin, retaining the water retaining ability of the epidermis, and retaining the elasticity of the skin. However, due to internal factors such as aging and external factors such as ultraviolet rays and active oxygen, the softness and moisturizing power of the skin decline, leading to aging phenomena such as wrinkles and sagging.
  • collagen is known to play an important role in the suppression and recovery of skin aging phenomenon.
  • a composition containing collagen or the synthesis of collagen is known.
  • a method of applying a composition containing a substance that promotes skin to the skin has been performed.
  • Ascorbic acid phosphate, retinoic acid, and the like are known as substances that promote collagen synthesis.
  • Ascorbic acid phosphate is a type of ascorbic acid derivative that is converted to vitamin C by transdermal absorption.
  • Vitamin C is one of the cell growth factors that induces the formation of cells by maturing the intercellular substances (extracellular matrix) with a collagen skeleton that only activates collagen synthesis. It has been clarified by an experiment of cell culture using ascorbic acid-2-phosphate Mg salt (APM) (see Non-Patent Document 1).
  • Retinoic acid is a derivative of vitamin A, and its physiological activity is about 300 times that of vitamin A. It is the body of biological activity of vitamin A in the body itself. In the United States, it has been approved by the FDA (Food and Drug Administration) as a therapeutic drug for skin and acne.
  • Non-Patent Document 2 reports that an alcohol extract of leaves of milobaran (Terminalia chebula) has an effect on wound healing. In an in vivo test using rats, It significantly promoted epithelialization, and a significant increase in protein, DNA and collagen components in the granulation and weaving was observed. It has been reported that the leaf power of milobaran has been isolated from keblagic acid, kebric acid, corilagin, and gallic acid (see Non-Patent Document 3).
  • Non-patent literature l Eur. J. Biochem, 174, p231 (1988)
  • Non-Patent Document 2 Phytother.Res, 16, p227 (2002)
  • Non-Patent Document 3 Bull.Central Leather Res.Inst., 8, p230 (1961)
  • the method of applying collagen to the skin surface to supply collagen to the skin does not essentially improve skin function because collagen has a high molecular structure and is not absorbed by the barrier function of the epidermis. I helped. Further, collagen synthesis promoting substances such as retinoic acid are desired to be further improved rather than being sufficiently satisfactory in terms of effects.
  • an object of the present invention is to provide a collagen synthesis promoter having a sufficient collagen synthesis promoting action and a high skin conditioning effect.
  • the collagen synthesis promoter of the present invention is characterized by comprising an active ingredient of an extract of fruit of milobaran (hereinafter also referred to as “mylobaran fruit extract”).
  • mylobaran fruit extract an extract of fruit of milobaran
  • the alcoholic extract of milobaran leaves has a wound healing effect and significantly increases the amount of collagen in the granulation tissue.
  • the extract of milobaran fruit is effective in promoting collagen.
  • the degree of the collagen synthesis promoting action of myrobalan leaf the details are unknown and it is difficult to obtain.
  • Milova None of the substances contained in the orchid leaf extract was known as to which substances contribute more to collagen synthesis.
  • the other collagen synthesis promoter of the present invention is one or more selected from the group consisting of chebulagic acid, chebulinic acid, gallic acid and corilagin. It is characterized by containing two or more active ingredients.
  • the collagen synthesis promoter of the present invention can be suitably used as an external preparation for skin, and can be suitably used as a skin quality improving agent for use.
  • the collagen synthesis promoter of the present invention can effectively promote the synthesis of collagen.
  • the collagen synthesis promoter of the present invention is used as an external preparation for skin, it is possible to give the skin freshness, texture, texture, and to maintain the water retaining ability of the epidermis.
  • FIG. 1 (a) A micrograph of the skin when a topical skin preparation containing milobalan fruit cocoon kiss is used, and (b) is a micrograph of the skin when only the base is applied.
  • the collagen synthesis promoter of the present invention contains a milobaran fruit extract as an active ingredient, but a milobaran fruit extract can be obtained by a conventional method.
  • the milobaran fruit is soaked or heated under reflux with an extraction solvent. Then, it is filtered, and the resulting extract can be obtained as it is or by concentrating it.
  • the concentrated or dried extract can be dissolved in a solvent and used again.
  • the extraction solvent any solvent that is usually used for extraction can be used, and examples thereof include water and organic solvents such as ethanol, 1,3-butylene glycol, propylene glycol, acetone, methanol, and ethyl acetate.
  • the other collagen synthesis promoter of the present invention comprises one or more active ingredients selected from the group consisting of keblagic acid, kebric acid, gallic acid and corilagin, which are components contained in the milobaran fruit extract.
  • keblagic acid and kevulinic acid that exhibit a high collagen synthesis promoting action and have a high content are used.
  • Each component can be obtained by extracting and isolating plant power or synthesizing by a known method.
  • the fruit strength of milobaran can be suitably obtained by extracting the milobaran fruit extract and then isolating it by the above method.
  • the isolation method is not particularly limited, but it can be suitably isolated by techniques such as liquid-liquid distribution, various chromatographies, and recrystallization.
  • Each of the components contained in the thus-obtained milobaran fruit extract and milobaran fruit extract has an excellent collagen synthesis promoting action.
  • the collagen synthesis promoter of the present invention can be used in various fields such as pharmaceuticals, quasi drugs, foods and cosmetics.
  • the collagen synthesis promoter of the present invention is used as a skin external preparation
  • the compounding amount of milobalan fruit extract and the components of kerobic acid, kebric acid, gallic acid and corilagin, which are the components of myrobalan fruit extract is usually preferably 0.0001 to 5% as a dry weight and more preferably 0.001 to 0.1% as a total weight in the total amount of the external preparation. Below this range, the effect of promoting collagen synthesis is hard to be fully exerted.If the content exceeds this range, the effect cannot be expected to increase, and it is not economical. This is preferable because of problems such as dyeing with crude drugs!
  • the skin external preparation of the present invention includes, in addition to the above-mentioned myrobalan fruit extract, other components that are usually used in skin external preparations such as cosmetics and pharmaceuticals within the range not impairing the effects of the present invention, for example, Moisturizer, oil component, surfactant, vitamins, proteolytic enzyme, thickener, preservative, powder, antioxidant, ultraviolet absorber, emulsifier, alcohol, color material, aqueous component, water, various A skin nutrient or the like can be appropriately blended as necessary.
  • other components that are usually used in skin external preparations such as cosmetics and pharmaceuticals within the range not impairing the effects of the present invention, for example, Moisturizer, oil component, surfactant, vitamins, proteolytic enzyme, thickener, preservative, powder, antioxidant, ultraviolet absorber, emulsifier, alcohol, color material, aqueous component, water, various A skin nutrient or the like can be appropriately blended as necessary.
  • humectant examples include polyhydric alcohols such as glycerin, propylene glycol, polyethylene glycol and 1,3 butylene glycol, sugar alcohols such as sorbit and mannitol, hyaluronate, chondroitin sulfate, chitosan and the like.
  • oils component examples include natural fats and oils such as soybean oil, nuka oil, apogado oil, almond oil, olive oil, cacao butter, sesame oil, persic oil, castor oil, coconut oil, mink oil, beef tallow, and lard. Hardened oils obtained by hydrogenation of these natural fats and oils, synthetic glycerides such as myristic acid glyceride, 2-ethylhexanoic acid glyceride, fats and oils such as diglyceride, jojoba oil, carnauba wax, whale wax, beeswax, lanolin, etc.
  • natural fats and oils such as soybean oil, nuka oil, apogado oil, almond oil, olive oil, cacao butter, sesame oil, persic oil, castor oil, coconut oil, mink oil, beef tallow, and lard.
  • Hardened oils obtained by hydrogenation of these natural fats and oils synthetic glycerides such as myristic acid glyceride, 2-
  • Waxes liquid paraffin, petrolatum, paraffin, microcrystalline wax, hydrocarbons such as ceresin, squalane, pristane, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid Higher fatty acids such as lanolinic acid and isostearic acid, lauryl alcohol monole, Higher alcohols such as cetinoleanoreconole, stearinoreanoreconole, oleinoleanoreconole, cholesterol, 2-hexyldecanol, jojoba alcohol, cetyl octanoate, myristyl lactate, cetyl lactate, myristic acid Examples include myristyl, octyldodecyl myristate, isopropyl myristate, isopropyl palmitate, isopropyl adipate, buty
  • surfactant examples include glycerin fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, tetraoleic acid polyoxyethylene sorbite, polyoxyethylene alkyl ether, Polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene castor oil, polyglycerin fatty acid ester, fatty acid monodalide, sucrose fatty acid ester, higher fatty acid al
  • Nonionic surfactants such as strength olamide, sodium a-olefin sulfonate, sodium lauryl sulfate, sodium cetyl sulfate, poly Sodium xylethylene lauryl sulfate, sulfosuccinic acid Sodium lauryl sulfonate, linear
  • Vitamins include, for example, vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin F, vitamin, vitamin P, vitamin U, carcin, ferulic acid, ⁇ -oryzanol, lipo
  • examples include acids, orotic acid and derivatives thereof.
  • the proteolytic enzyme include pepsin, trypsin, chymotrypsin, cathebcin, papain, bromelain, ficin, and bacteria, yeast, and mold-derived proteases.
  • Examples of the thickener include water-soluble polymer compounds such as carboxybule polymer, carboxymethylcellulose, polybulal alcohol, carrageenan, gelatin, xanthan gum, polyacrylate, and sodium chloride and potassium salt.
  • An inorganic salt is mentioned.
  • Examples of the preservative include phenoxyethanol, methyl paraben, ethyl paraben, butyparaben, sodium benzoate and the like.
  • powders include talc, sericite, my strength, kaolin, silica, bentonite, vermiculite, zinc white, mica, mica titanium, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, bengara, iron oxide, Examples include ultramarine blue.
  • Other ingredients include fragrances, pigments, fungicides and the like.
  • the dosage form of the external preparation for skin of the present invention is arbitrary.
  • it can be made into a lotion, a milk, a cream, an ointment, a dispersion, a gel, an aerosol, a nose, a bath, and the like. it can.
  • Human fibroblasts (Detroit551) were cultured in MEM medium containing 10% FBS, 1% NEAA, lmmol / L sodium pyruvate under conditions of 37 ° C, 5% CO-95% air.
  • the cells were cultured for 3 days under 2 ir conditions.
  • the samples are, as examples, myrobalan fruit extract (Example 1), keblagic acid (Example 2), gallic acid (Example 3), and kerblic acid (Example 3), which are the main components of myrobalan fruit extract. 4) and corilagin (Example 5), as a comparative example, quebrin, as a reference example, L-ascorbic acid 2-phosphate ester Mg salt (APM), retinoic acid, which is known to have a conventional ability to promote collagen synthesis, Each sample was adjusted to a concentration of 25, 50, lOOppm and used.
  • APM L-ascorbic acid 2-phosphate ester Mg salt
  • Kebric acid 1 160.7 ⁇ 55.0 "521.7 ⁇ 35.8” 495.0 ⁇ 32.0 "4
  • Kebranin 1 1 1.9 ⁇ 9.1 58.1 ⁇ 28.2 140.6 ⁇ 18.4 1
  • a cream formulation containing 0.5% milobaran fruit extract (hereinafter referred to as “Milobalan formulation”). A cream ", u) was prepared.
  • a powder bath containing milobaran fruit extract was prepared by uniformly mixing all raw materials.
  • the alcohol phase is added to the aqueous phase to prepare a stock solution, the stock solution is put into a can, and filled with a gas such as LPG or butane. Aerosol product) was prepared.
  • the oil phase and the aqueous phase were each heated to 70 ° C for complete dissolution.
  • the oil phase was added to the aqueous phase to emulsify, and after cooling, the added phase was added to prepare a body cream containing a myloparan fruit extract with pH 6.1.
  • Tri cabril 'cabric acid
  • the oil phase and the aqueous phase were each heated to 70 ° C to be completely dissolved.
  • An oil phase was added to the aqueous phase to emulsify, and after cooling, a finely pulverized powder phase and an additional phase were added to prepare a sunscreen tarm containing SPF20 milobaran fruit extract.
  • Titanium oxide ⁇ Keyed anhydride composite 2.0
  • the skin gloss, firmness, softness, crispness, dullness, texture and wrinkle before and after application for 1 month were evaluated according to the following evaluation criteria.
  • Fig. 1 shows the results of micrographs after application for 1 month.
  • A shows the case where a topical skin preparation containing milobalan fruit juice is applied
  • (b) shows the case where only the base is applied. From the photograph, it can be seen that the texture is better when using a topical skin preparation containing a milobaran fruit extract compared to the base alone. In addition, moisturizing power and elasticity improved, and dullness disappeared.

Abstract

A collagen synthesis promoter capable of exhibiting a satisfactory collagen synthesis promoting activity and a high skin conditioning potency. There is provided a collagen synthesis promoter comprising as an active ingredient an extract from the fruit of myrobalan, and provided a collagen synthesis promoter comprising as an active ingredient one or two or more members selected from the group consisting of chebulagic acid, chebulinic acid, gallic acid and corilagin. The provided collagen synthesis promoter is suitable for use as a skin external preparation or skin quality improver; and can impart moistness and suppleness to the skin, can effect texture conditioning and can sustain the water retaining power of superficial skin.

Description

明 細 書  Specification
コラーゲン合成促進剤  Collagen synthesis promoter
技術分野  Technical field
[0001] 本発明はコラーゲン合成促進剤に関し、詳しくは、繊維芽細胞のコラーゲン合成を 促進させ、肌にみずみずしさ、ハリを与え、表皮の保水力を保持することを目的とした コラーゲン合成促進剤に関する。  TECHNICAL FIELD [0001] The present invention relates to a collagen synthesis promoter, and more specifically, a collagen synthesis promoter aimed at promoting collagen synthesis in fibroblasts, imparting freshness and firmness to the skin, and maintaining the water retaining ability of the epidermis. About.
背景技術  Background art
[0002] コラーゲンは、動物の結合糸且織を構成する主要蛋白質であり、特にヒトの体の総蛋 白質の 30%近くをコラーゲンが占める。皮膚においてコラーゲンは肌のみずみずし さ、ノ、リを与え、表皮の保水力を保持し、肌の弾力を保持する機能を有している。しか し、加齢等の内的因子および紫外線、活性酸素等の外的因子により、皮膚の柔軟性 、保湿力等は衰え、シヮ、たるみ等の老化現象につながる。  [0002] Collagen is the main protein that forms the binding thread and weave of animals. Collagen occupies nearly 30% of the total protein of the human body. In the skin, collagen has a function of imparting freshness, thickness and thickness to the skin, retaining the water retaining ability of the epidermis, and retaining the elasticity of the skin. However, due to internal factors such as aging and external factors such as ultraviolet rays and active oxygen, the softness and moisturizing power of the skin decline, leading to aging phenomena such as wrinkles and sagging.
[0003] これらは、真皮の細胞外マトリックスを産生する細胞数の減少、細胞分裂速度の衰 え等の細胞機能の低下や、コラーゲン線維の減少および変性、皮下脂肪組織の減 少等により、皮膚の弛緩及び弾力性の損失が起こることが原因となって発生する。  [0003] These are caused by a decrease in the number of cells that produce the extracellular matrix of the dermis, a decrease in cell functions such as a decrease in the cell division rate, a decrease and degeneration of collagen fibers, a decrease in subcutaneous adipose tissue, and the like. Occurs due to relaxation and loss of elasticity.
[0004] 特にコラーゲンは皮膚の老化現象の抑制および回復に重要な役割を持つことが知 られており、皮膚の老化現象の改善を目的として、コラーゲンを含有する組成物、ま たはコラーゲンの合成を促進する物質を含有する組成物を皮膚に塗布する方法が 行われている。  [0004] In particular, collagen is known to play an important role in the suppression and recovery of skin aging phenomenon. For the purpose of improving skin aging phenomenon, a composition containing collagen or the synthesis of collagen is known. A method of applying a composition containing a substance that promotes skin to the skin has been performed.
[0005] コラーゲン合成を促進する物質として、ァスコルビン酸リン酸、レチノイン酸等が知ら れている。ァスコルビン酸リン酸はァスコルビン酸誘導体の一種であり、経皮吸収され ることによりビタミン Cに変換される。ビタミン Cはコラーゲン合成を活性ィ匕するだけで なぐコラーゲンを骨格とする細胞間物質 (細胞外マトリックス)を成熟させ、細胞の組 織形成を誘導する細胞増殖因子の一つでもあることが、 Lーァスコルビン酸ー2—リ ン酸エステル Mg塩 (APM)を使った細胞培養の実験により明らかにされている(非 特許文献 1参照)。  [0005] Ascorbic acid phosphate, retinoic acid, and the like are known as substances that promote collagen synthesis. Ascorbic acid phosphate is a type of ascorbic acid derivative that is converted to vitamin C by transdermal absorption. Vitamin C is one of the cell growth factors that induces the formation of cells by maturing the intercellular substances (extracellular matrix) with a collagen skeleton that only activates collagen synthesis. It has been clarified by an experiment of cell culture using ascorbic acid-2-phosphate Mg salt (APM) (see Non-Patent Document 1).
[0006] また、レチノイン酸はビタミン Aの誘導体で、生理活性はビタミン Aの約 300倍であり 、ビタミン A類の体内での生理活性の本体そのものである。米国ではシヮ、二キビの治 療医薬品として、 FDA (米食品医薬局)に認可されている。 [0006] Retinoic acid is a derivative of vitamin A, and its physiological activity is about 300 times that of vitamin A. It is the body of biological activity of vitamin A in the body itself. In the United States, it has been approved by the FDA (Food and Drug Administration) as a therapeutic drug for skin and acne.
[0007] 更に、非特許文献 2にはミロバラン(Terminalia chebula)の葉のアルコール抽出物 が創傷治癒に対して、効果があることが報告されており、ラットを用いた in vivoの試 験において、上皮化を有意に促進し、肉芽糸且織中のたんぱく質、 DNA、コラーゲン 成分の有意な増加が観察された。なお、ミロバランの葉力もはケブラグ酸、ケブリン酸 、コリラギン、没食子酸が単離されたとの報告もなされている (非特許文献 3参照)。 非特許文献 l : Eur.J.Biochem,174,p231(1988) [0007] Further, Non-Patent Document 2 reports that an alcohol extract of leaves of milobaran (Terminalia chebula) has an effect on wound healing. In an in vivo test using rats, It significantly promoted epithelialization, and a significant increase in protein, DNA and collagen components in the granulation and weaving was observed. It has been reported that the leaf power of milobaran has been isolated from keblagic acid, kebric acid, corilagin, and gallic acid (see Non-Patent Document 3). Non-patent literature l: Eur. J. Biochem, 174, p231 (1988)
非特許文献 2: Phytother.Res,16,p227(2002)  Non-Patent Document 2: Phytother.Res, 16, p227 (2002)
非特許文献 3 : Bull.Central Leather Res.Inst.,8,p230(1961)  Non-Patent Document 3: Bull.Central Leather Res.Inst., 8, p230 (1961)
発明の開示  Disclosure of the invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0008] コラーゲンを皮膚に供給するためにコラーゲンを皮膚表面に塗布する方法は、コラ 一ゲンが高分子構造を有し表皮のバリアー機能により吸収されないため、本質的に 皮膚機能を改善するものではな力つた。また、レチノイン酸等のコラーゲン合成促進 物質は、効果の面で十分に満足できるものではなぐ更なる向上が望まれる。  [0008] The method of applying collagen to the skin surface to supply collagen to the skin does not essentially improve skin function because collagen has a high molecular structure and is not absorbed by the barrier function of the epidermis. I helped. Further, collagen synthesis promoting substances such as retinoic acid are desired to be further improved rather than being sufficiently satisfactory in terms of effects.
[0009] そこで、本発明の目的は十分なコラーゲン合成促進作用、高い整肌効果を有する コラーゲン合成促進剤を提供することにある。  Accordingly, an object of the present invention is to provide a collagen synthesis promoter having a sufficient collagen synthesis promoting action and a high skin conditioning effect.
課題を解決するための手段  Means for solving the problem
[0010] 本発明者は上記課題を解決するために、鋭意検討した結果、ミロバラン (Terminalia chebula)の果実 (訶子)が高 、コラーゲン促進作用を有する成分を含有して!/、ること 見出し、本発明を完成するに至った。即ち、本発明のコラーゲン合成促進剤はミロバ ランの果実の抽出物(以下、「ミロバラン果実エキス」とも言う)を有効成分することを特 徴とするものである。上述したようにミロバランの葉のアルコール抽出物が創傷治癒 効果を有し、肉芽組織中のコラーゲン成分を有意に増カロさせることは知られているが 、ミロバランの果実の抽出物がコラーゲン促進作用に対し、より優れた効果を有する ことは知られていな力つた。また、ミロバランの葉のコラーゲン合成促進作用の程度に 関し、詳細は不明であり、入手が困難であるという問題点も有している。更に、ミロバ ランの葉の抽出液に含まれる物質のうち、どの物質がコラーゲン合成に、より寄与し て 、るかに関しても知られては 、なかった。 [0010] As a result of intensive studies to solve the above problems, the present inventor has found that the fruit (coconut) of Milobaran (Terminalia chebula) is high and contains a component having a collagen promoting action! /. The present invention has been completed. That is, the collagen synthesis promoter of the present invention is characterized by comprising an active ingredient of an extract of fruit of milobaran (hereinafter also referred to as “mylobaran fruit extract”). As mentioned above, it is known that the alcoholic extract of milobaran leaves has a wound healing effect and significantly increases the amount of collagen in the granulation tissue. However, the extract of milobaran fruit is effective in promoting collagen. On the other hand, it was not known to have a better effect. In addition, regarding the degree of the collagen synthesis promoting action of myrobalan leaf, the details are unknown and it is difficult to obtain. In addition, Milova None of the substances contained in the orchid leaf extract was known as to which substances contribute more to collagen synthesis.
[0011] 本発明の他のコラーゲン合成促進剤は、ケブラグ酸(chebulagic acid)、ケブリン酸( chebulinic acid)、没食子酸(gallic acid)およびコリラギン(corilagin)力 なる群から選 択される 1種または 2種以上を有効成分することを特徴とするものである。 [0011] The other collagen synthesis promoter of the present invention is one or more selected from the group consisting of chebulagic acid, chebulinic acid, gallic acid and corilagin. It is characterized by containing two or more active ingredients.
[0012] 更に、本発明のコラーゲン合成促進剤は皮膚外用剤として好適に使用することが でき、また、用途に関しては、肌質改善剤として好適に使用することができる。 [0012] Furthermore, the collagen synthesis promoter of the present invention can be suitably used as an external preparation for skin, and can be suitably used as a skin quality improving agent for use.
発明の効果  The invention's effect
[0013] 本発明のコラーゲン合成促進剤により、コラーゲンの合成を効果的に促進すること ができる。また、本発明のコラーゲン合成促進剤を皮膚外用剤として用いた場合には 、肌にみずみずしさ、ノ、リを与え、キメを整え、また表皮の保水力を保持することが可 能である。  [0013] The collagen synthesis promoter of the present invention can effectively promote the synthesis of collagen. In addition, when the collagen synthesis promoter of the present invention is used as an external preparation for skin, it is possible to give the skin freshness, texture, texture, and to maintain the water retaining ability of the epidermis.
図面の簡単な説明  Brief Description of Drawings
[0014] [図 1] (a)ミロバラン果実ヱキスを含有する皮膚外用剤を用いた場合の肌、(b)は基剤 のみを塗布した場合の肌の顕微鏡写真である。  [0014] [Fig. 1] (a) A micrograph of the skin when a topical skin preparation containing milobalan fruit cocoon kiss is used, and (b) is a micrograph of the skin when only the base is applied.
発明を実施するための最良の形態  BEST MODE FOR CARRYING OUT THE INVENTION
[0015] 以下、本発明の好適実施形態につき具体的に説明する。本発明のコラーゲン合成 促進剤は、ミロバラン果実エキスを有効成分とするものであるが、ミロバラン果実ェキ スは常法により得ることができ、例えば、ミロバランの果実を抽出溶媒と共に浸漬また は加熱還流した後、濾過し、得られた抽出液をそのまま、またはこれを濃縮して得る ことができる。また、濃縮または乾燥させた抽出物を、再度溶媒に溶解させて用いる こともできる。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、水や、エタノール、 1, 3—ブチレングリコール、プロピレングリコ ール、アセトン、メタノール、酢酸ェチルなどの有機溶媒が挙げられ、それら力 選ば れる何れ力 1種、または任意に組み合わせた 2種以上を使用することができる。抽出 の条件は特に限定されないが、例えば、ミロバランの果実 1重量部に対し、溶媒 2〜1 00重量部、その際の抽出時の温度及び時間は、 0〜: L00°Cの温度で 10分〜 1週間 とすることができる。 [0016] また、本発明の他のコラーゲン合成促進剤は、ミロバラン果実エキスの含有成分で あるケブラグ酸、ケブリン酸、没食子酸およびコリラギンからなる群から選択される 1種 または 2種以上を有効成分とするものである力 好ましくは、高いコラーゲン合成促進 作用を示し、かつ含有量の多いケブラグ酸およびケブリン酸である。それぞれの成分 は植物力 抽出、単離することにより、または既知の方法により合成することにより得 ることができる。上記の方法によりミロバランの果実力もミロバラン果実エキスを抽出し た後、単離することにより、それぞれ好適に得ることができる。単離方法は特に制限さ れるものではないが、液 液分配、各種クロマトグラフィー、再結晶化などの手法によ り好適に単離することができる。このようにして得られたミロバラン果実エキスおよびミ ロバラン果実エキスのそれぞれの含有成分は、優れたコラーゲン合成促進作用を有 する。本発明のコラーゲン合成促進剤は、医薬品、医薬部外品、食品、化粧品等の 各種分野において利用することができる。 Hereinafter, preferred embodiments of the present invention will be specifically described. The collagen synthesis promoter of the present invention contains a milobaran fruit extract as an active ingredient, but a milobaran fruit extract can be obtained by a conventional method. For example, the milobaran fruit is soaked or heated under reflux with an extraction solvent. Then, it is filtered, and the resulting extract can be obtained as it is or by concentrating it. In addition, the concentrated or dried extract can be dissolved in a solvent and used again. As the extraction solvent, any solvent that is usually used for extraction can be used, and examples thereof include water and organic solvents such as ethanol, 1,3-butylene glycol, propylene glycol, acetone, methanol, and ethyl acetate. Any one of these forces can be used, or two or more can be used in any combination. The extraction conditions are not particularly limited. For example, for 1 part by weight of milobaran fruit, 2 to 100 parts by weight of solvent, and the temperature and time during extraction are 0 to 10 minutes at a temperature of L00 ° C. ~ 1 week can be. [0016] In addition, the other collagen synthesis promoter of the present invention comprises one or more active ingredients selected from the group consisting of keblagic acid, kebric acid, gallic acid and corilagin, which are components contained in the milobaran fruit extract. Preferably, keblagic acid and kevulinic acid that exhibit a high collagen synthesis promoting action and have a high content are used. Each component can be obtained by extracting and isolating plant power or synthesizing by a known method. The fruit strength of milobaran can be suitably obtained by extracting the milobaran fruit extract and then isolating it by the above method. The isolation method is not particularly limited, but it can be suitably isolated by techniques such as liquid-liquid distribution, various chromatographies, and recrystallization. Each of the components contained in the thus-obtained milobaran fruit extract and milobaran fruit extract has an excellent collagen synthesis promoting action. The collagen synthesis promoter of the present invention can be used in various fields such as pharmaceuticals, quasi drugs, foods and cosmetics.
[0017] 上記本発明のコラーゲン合成促進剤を皮膚外用剤として使用する場合、ミロバラン 果実エキスならびにミロバラン果実エキスの含有成分であるケブラグ酸、ケブリン酸、 没食子酸およびコリラギンの配合量は、有効成分の種類、剤型等によっても異なるが 、通常、好ましくは総量として外用剤全量中に乾燥重量として 0. 0001〜5%、より好 ましくは 0. 001-0. 1%である。この範囲を下回るとコラーゲン合成促進効果が十分 に発揮され難ぐこの範囲を超えて配合すると効果の上昇が期待できず、経済性に 欠ける他、ベたつき、生薬特有のにおい、使用感の低下、生薬による染着の問題な どが起こるので好ましくな!/、。  [0017] When the collagen synthesis promoter of the present invention is used as a skin external preparation, the compounding amount of milobalan fruit extract and the components of kerobic acid, kebric acid, gallic acid and corilagin, which are the components of myrobalan fruit extract, Although it varies depending on the type, dosage form, etc., it is usually preferably 0.0001 to 5% as a dry weight and more preferably 0.001 to 0.1% as a total weight in the total amount of the external preparation. Below this range, the effect of promoting collagen synthesis is hard to be fully exerted.If the content exceeds this range, the effect cannot be expected to increase, and it is not economical. This is preferable because of problems such as dyeing with crude drugs!
[0018] 本発明の皮膚外用剤には、上記ミロバラン果実エキスに加えて、本発明の効果を 損なわない範囲内で、通常化粧料や医薬品等の皮膚外用剤に用いられる他の成分 、例えば、保湿剤、油性成分、界面活性剤、ビタミン類、蛋白分解酵素、増粘剤、防 腐剤、粉体、酸化防止剤、紫外線吸収剤、乳化剤、アルコール類、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。  [0018] The skin external preparation of the present invention includes, in addition to the above-mentioned myrobalan fruit extract, other components that are usually used in skin external preparations such as cosmetics and pharmaceuticals within the range not impairing the effects of the present invention, for example, Moisturizer, oil component, surfactant, vitamins, proteolytic enzyme, thickener, preservative, powder, antioxidant, ultraviolet absorber, emulsifier, alcohol, color material, aqueous component, water, various A skin nutrient or the like can be appropriately blended as necessary.
[0019] 保湿剤としては、例えば、グリセリン、プロピレングリコール、ポリエチレングリコール 、 1, 3 ブチレングリコール等の多価アルコール、ソルビット、マンニット等の糖アルコ ール、ヒアルロン酸塩、コンドロイチン硫酸塩、キトサン等の水溶性高分子、尿素、乳 酸ナトリウム、ピロリドンカルボン酸塩等が挙げられる。 [0019] Examples of the humectant include polyhydric alcohols such as glycerin, propylene glycol, polyethylene glycol and 1,3 butylene glycol, sugar alcohols such as sorbit and mannitol, hyaluronate, chondroitin sulfate, chitosan and the like. Water-soluble polymer, urea, milk Examples thereof include sodium acid and pyrrolidone carboxylate.
[0020] 油性成分としては、例えば、大豆油、ヌカ油、アポガド油、アーモンド油、ォリーブ油 、カカオ脂、ゴマ油、パーシック油、ヒマシ油、ヤシ油、ミンク油、牛脂、豚脂等の天然 油脂、これらの天然油脂を水素添加して得られる硬化油及びミリスチン酸グリセリド、 2—ェチルへキサン酸グリセリド等の合成グリセリド、ジグリセリド等の油脂類、ホホバ 油、カルナウパロウ、鯨ロウ、ミツロウ、ラノリン等のロウ類、流動パラフィン、ワセリン、 パラフィン、マイクロクリスタリンワックス、セレシン、スクヮラン、プリスタン等の炭化水 素類、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、ベヘン酸、ォレイン酸、リ ノール酸、リノレン酸、ラノリン酸、イソステアリン酸等の高級脂肪酸類、ラウリルアルコ 一ノレ、セチノレアノレコーノレ、ステアリノレアノレコーノレ、ォレイノレアノレコーノレ、コレステロ一 ル、 2—へキシルデカノール、ホホバアルコール等の高級アルコール類、オクタン酸 セチル、乳酸ミリスチル、乳酸セチル、ミリスチン酸ミリスチル、ミリスチン酸オタチルド デシル、ミリスチン酸イソプロピル、パルミチン酸イソプロピル、アジピン酸イソプロピル 、ステアリン酸プチル、ォレイン酸デシル、イソステアリン酸コレステロール等のエステ ル類、精油類およびシリコーン油類が挙げられる。  [0020] Examples of the oil component include natural fats and oils such as soybean oil, nuka oil, apogado oil, almond oil, olive oil, cacao butter, sesame oil, persic oil, castor oil, coconut oil, mink oil, beef tallow, and lard. Hardened oils obtained by hydrogenation of these natural fats and oils, synthetic glycerides such as myristic acid glyceride, 2-ethylhexanoic acid glyceride, fats and oils such as diglyceride, jojoba oil, carnauba wax, whale wax, beeswax, lanolin, etc. Waxes, liquid paraffin, petrolatum, paraffin, microcrystalline wax, hydrocarbons such as ceresin, squalane, pristane, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid Higher fatty acids such as lanolinic acid and isostearic acid, lauryl alcohol monole, Higher alcohols such as cetinoleanoreconole, stearinoreanoreconole, oleinoleanoreconole, cholesterol, 2-hexyldecanol, jojoba alcohol, cetyl octanoate, myristyl lactate, cetyl lactate, myristic acid Examples include myristyl, octyldodecyl myristate, isopropyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, decyl oleate, cholesterol isostearate, essential oils, and silicone oils.
[0021] 界面活性剤としては、例えば、グリセリン脂肪酸エステル、プロピレングリコール脂 肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エス テル、テトラオレイン酸ポリオキシエチレンソルビット、ポリオキシエチレンアルキルェ 一テル、ポリオキシエチレンポリオキシプロピレンアルキルエーテル、ポリオキシェチ レンアルキルフエ-ルエーテル、ポリオキシエチレン脂肪酸エステル、ポリエチレング リコール脂肪酸エステル、ポリオキシエチレンヒマシ油、ポリグリセリン脂肪酸エステル 、脂肪酸モノダリセライド、ショ糖脂肪酸エステル、高級脂肪酸アル力ノールアミド等 の非イオン性界面活性剤、 a—ォレフインスルホン酸ナトリウム、ラウリル硫酸ナトリウ ム、セチル硫酸ナトリウム、ポリオキシエチレンラウリル硫酸ナトリウム、スルホコハク酸 ラウリルニナトリウム、直鎖アルキルベンゼンスルホン酸塩、分岐鎖アルキルベンゼン スルホン酸塩、アルキル硫酸塩、アルケニル硫酸塩、エチレンオキサイド及び Z又は プロピレンオキサイドを付カ卩したアルキルエーテルカルボン酸塩又はアルケ-ルエー テルカルボン酸塩、 a—スルホ脂肪酸エステル、アミノ酸型界面活性剤、リン酸エス テル型界面活性剤、タウリン型界面活性剤、アマイドエーテルサルフェート型界面活 性剤等の陰イオン性界面活性剤、カルボキシベタイン型、アミノカルボン酸、スルホ ベタイン型等の両性界面活性剤および 4級アンモ-ゥム塩等の陽イオン性界面活性 剤が挙げられる力 安全性の面力ゝら非イオン性界面活性剤が特に好まし ヽ。 [0021] Examples of the surfactant include glycerin fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, tetraoleic acid polyoxyethylene sorbite, polyoxyethylene alkyl ether, Polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene castor oil, polyglycerin fatty acid ester, fatty acid monodalide, sucrose fatty acid ester, higher fatty acid al Nonionic surfactants such as strength olamide, sodium a-olefin sulfonate, sodium lauryl sulfate, sodium cetyl sulfate, poly Sodium xylethylene lauryl sulfate, sulfosuccinic acid Sodium lauryl sulfonate, linear alkylbenzene sulfonate, branched alkylbenzene sulfonate, alkyl sulfate, alkenyl sulfate, alkyl ether carboxylic acid with ethylene oxide and Z or propylene oxide Salt or alkenyl tercarboxylate, a —sulfo fatty acid ester, amino acid type surfactant, phosphoric acid ester Anionic surfactants such as tellurium type surfactants, taurine type surfactants, amide ether sulfate type surfactants, amphoteric surfactants such as carboxybetaine type, aminocarboxylic acid, sulfobetaine type and quaternary ammo -The ability to include cationic surfactants such as um salt Nonionic surfactants are particularly preferred in terms of safety.
[0022] ビタミン類としては、例えば、ビタミン A、ビタミン B、ビタミン C、ビタミン D、ビタミン E 、ビタミン F、ビタミン 、ビタミン P、ビタミン U、カル-チン、フェルラ酸、 γ—オリザノ ール、リポ酸、ォロット酸及びその誘導体等が挙げられる。蛋白分解酵素としては、例 えば、ペプシン、トリプシン、キモトリブシン、カテブシン、パパイン、ブロメライン、フィ シン及び細菌、酵母、カビ由来のプロテアーゼ等が挙げられる。  [0022] Vitamins include, for example, vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin F, vitamin, vitamin P, vitamin U, carcin, ferulic acid, γ-oryzanol, lipo Examples include acids, orotic acid and derivatives thereof. Examples of the proteolytic enzyme include pepsin, trypsin, chymotrypsin, cathebcin, papain, bromelain, ficin, and bacteria, yeast, and mold-derived proteases.
[0023] 増粘剤としては、例えばカルボキシビュルポリマー、カルボキシメチルセルロース、 ポリビュルアルコール、カラギーナン、ゼラチン、キサンタンガム、ポリアクリル酸塩等 の水溶性高分子化合物、塩ィ匕ナトリウム、塩ィ匕カリウム等の無機塩が挙げられる。防 腐剤としては、例えばフエノキシエタノール、メチルパラベン、ェチルパラベン、ブチ ルパラベン、安息香酸ナトリウム等が挙げられる。粉体としては、例えばタルク、セリサ イト、マイ力、カオリン、シリカ、ベントナイト、バーミキユライト、亜鉛華、雲母、雲母チタ ン、酸化チタン、酸化マグネシウム、酸化ジルコニウム、硫酸バリウム、ベンガラ、酸化 鉄、群青等が挙げられる。その他の成分としては、香料、色素、殺菌剤等を挙げるこ とがでさる。  [0023] Examples of the thickener include water-soluble polymer compounds such as carboxybule polymer, carboxymethylcellulose, polybulal alcohol, carrageenan, gelatin, xanthan gum, polyacrylate, and sodium chloride and potassium salt. An inorganic salt is mentioned. Examples of the preservative include phenoxyethanol, methyl paraben, ethyl paraben, butyparaben, sodium benzoate and the like. Examples of powders include talc, sericite, my strength, kaolin, silica, bentonite, vermiculite, zinc white, mica, mica titanium, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, bengara, iron oxide, Examples include ultramarine blue. Other ingredients include fragrances, pigments, fungicides and the like.
[0024] また、本発明の皮膚外用剤の剤型は任意であり、例えばィ匕粧水、乳液、クリーム、 軟膏、分散液、ゲル状、エアゾール、ノ^ク、入浴剤などにすることができる。  [0024] In addition, the dosage form of the external preparation for skin of the present invention is arbitrary. For example, it can be made into a lotion, a milk, a cream, an ointment, a dispersion, a gel, an aerosol, a nose, a bath, and the like. it can.
実施例  Example
[0025] 以下、本発明を実施例に従い、詳細に説明する。  Hereinafter, the present invention will be described in detail according to examples.
麵列 1  Row 1
ミロバラン ヱキスの調製例  Preparation example of mirobalan ラ ン kiss
ミロバランの果実(乾燥品) 20gに 30%エタノール 20mLを加えて 2時間加熱し、放 冷した。放冷後、濾過を行い、濾液を減圧乾固した。その結果、 7. 61gのミロバラン 果実エキスを得ることができた。また、別に、 60%アセトンにて室温抽出して得たミロ バラン果実エキス 50. 28gから不溶物を濾去した後、 Sephadex LH- 20 (フアルマシア 製)、 MCI gel CHP20P (三菱ィ匕学 (株)製)やセルロース、 ODSゲルを用いた各種カラ ムクロマトグラフィーに付すことにより分離精製した結果、下記の表 1に示す収量にて ケブラグ酸、没食子酸、ケブリン酸、ケブラニン (chebulanin)およびコリラギンが得られ た。 To 20 g of myrobalan fruit (dried product), 20 mL of 30% ethanol was added, heated for 2 hours, and allowed to cool. After allowing to cool, filtration was performed, and the filtrate was dried under reduced pressure. As a result, 7.61 g of milobaran fruit extract could be obtained. Separately, the insoluble matter was filtered off from 50.28 g of Myrobalan fruit extract obtained by room temperature extraction with 60% acetone, and then Sephadex LH-20 (Farmasia) was removed. ), MCI gel CHP20P (Mitsubishi Chemical Co., Ltd.), cellulose, and various column chromatography using ODS gel. Gallic acid, kebulinic acid, chebulanin and corilagin were obtained.
[0026] [表 1]  [0026] [Table 1]
Figure imgf000008_0001
Figure imgf000008_0001
[0027] 実験例 2 [0027] Experimental Example 2
コラーゲン合成 谁作用 認試,験  Collagen synthesis
10%FBS、 1%NEAA、 lmmol/Lピルビン酸ナトリウムを含む MEM培地により 、 37°C、 5%CO—95%airの条件下にて、ヒトの繊維芽細胞(Detroit551)を培養し  Human fibroblasts (Detroit551) were cultured in MEM medium containing 10% FBS, 1% NEAA, lmmol / L sodium pyruvate under conditions of 37 ° C, 5% CO-95% air.
2  2
た。次に、トリプシン処理により細胞を集め 2 X 105個 ZmLに調整し、 96穴マイクロプ レートに 100 /z Lずつ播種した。 37°C、 5%CO— 95%airの条件下にてー晚培養後 It was. Next, cells were collected by trypsin treatment, adjusted to 2 × 10 5 ZmL, and seeded at 100 / zL each in a 96-well microplate. Under conditions of 37 ° C, 5% CO—95% air after sputum culture
2  2
、試料を含む 0· 5%FBS MEM培地(150 L)に交換し、 37。C、 5%CO— 95%a  Replace the sample with 0.5% FBS MEM medium (150 L) containing 37. C, 5% CO—95% a
2 irの条件下にて 3日間培養した。なお、試料は、実施例としてミロバラン果実エキス( 実施例 1)、ミロバラン果実エキスの主要な含有物質であるケブラグ酸 (実施例 2)、没 食子酸 (実施例 3)、ケブリン酸 (実施例 4)およびコリラギン (実施例 5)、比較例として ケブラニン、参考例として従来力 コラーゲン合成促進作用を有すると知られている L ーァスコルビン酸 2—リン酸エステル Mg塩 (APM)、レチノイン酸を用い、各試料 を 25、 50、 lOOppmの濃度に調整し、使用した。  The cells were cultured for 3 days under 2 ir conditions. In addition, the samples are, as examples, myrobalan fruit extract (Example 1), keblagic acid (Example 2), gallic acid (Example 3), and kerblic acid (Example 3), which are the main components of myrobalan fruit extract. 4) and corilagin (Example 5), as a comparative example, quebrin, as a reference example, L-ascorbic acid 2-phosphate ester Mg salt (APM), retinoic acid, which is known to have a conventional ability to promote collagen synthesis, Each sample was adjusted to a concentration of 25, 50, lOOppm and used.
[0028] 培養後の培養上清 90 μ Lを ELISAプレートに移し、抗ヒトコラーゲンタイプ 1抗体 を用いた ELISA法により、コラーゲン合成量を測定した。定量はヒトコラーゲンタイプ 1を標準品とする検量線を用いた。コラーゲン産生促進率は、試料無添加時の値を 1 00%として算出し、その結果を下記の表 2に示す。  [0028] 90 μL of the culture supernatant after the culture was transferred to an ELISA plate, and the amount of collagen synthesis was measured by ELISA using an anti-human collagen type 1 antibody. A calibration curve using human collagen type 1 as a standard was used for quantification. The collagen production promotion rate was calculated with the value when no sample was added as 100%, and the results are shown in Table 2 below.
[0029] [表 2] コント口一ルに対する合成量の割合(%) [0029] [Table 2] Ratio of composition amount to control mouth (%)
試料  Sample
試料濃度(lOOppm) 試料濃度(50ppm) έ式料濃度(25ppm) 実施例  Sample concentration (lOOppm) Sample concentration (50ppm) 料 Type material concentration (25ppm)
ミロバラン果実エキス 657.4 ±77.3·* 353.5± 106.1* 262.4±8.2" Myrobalan fruit extract 657.4 ± 77.3 * 353.5 ± 106.1 * 262.4 ± 8.2 "
1 1
実施例  Example
ケブラグ酸 755.6±73.9" 517.8 ±53.8" 263.7 ±19.9"* Keblagic acid 755.6 ± 73.9 "517.8 ± 53.8" 263.7 ± 19.9 "*
2 2
実施例  Example
没食子酸 864.6 ±54.2" 460.0 ±27.8" 336.6 ± 12.8** 3  Gallic acid 864.6 ± 54.2 "460.0 ± 27.8" 336.6 ± 12.8 ** 3
実施例  Example
ケブリン酸 1 160.7 ±55.0" 521.7±35.8" 495.0±32.0" 4  Kebric acid 1 160.7 ± 55.0 "521.7 ± 35.8" 495.0 ± 32.0 "4
実施例  Example
コリラギン 236.8±31.5' 253.1 ±75.6' 173.1 ± 10.7* 5  Collagen 236.8 ± 31.5 '253.1 ± 75.6' 173.1 ± 10.7 * 5
比較例  Comparative example
ケブラニン 1 1 1.9±9.1 58.1 ±28.2 140.6 ± 18.4 1  Kebranin 1 1 1.9 ± 9.1 58.1 ± 28.2 140.6 ± 18.4 1
参考例  Reference example
AP 307.7 ±27.7" 436.6±58.4** 307.0±24.1" 1  AP 307.7 ± 27.7 "436.6 ± 58.4 ** 307.0 ± 24.1" 1
参考例  Reference example
レチノイン酸 292.8 ±22.2" 123.8±36.6 234.1 ± 14.5" Retinoic acid 292.8 ± 22.2 "123.8 ± 36.6 234.1 ± 14.5"
2 2
π=5 ** pぐ 0.005 * pく 0.05  π = 5 ** p 0.005 * p 0.05
[0030] 上記表 2より、実施例すべてにおいて有意にコラーゲン合成促進作用を示し、ミロ パランの果実の抽出物(実施例 1)、ケブラグ酸 (実施例 2)、没食子酸 (実施例 3)およ びケブリン酸 (実施例 4)は、参考例と比較してもより高いコラーゲン合成促進作用を 有することが分かる。 [0030] From Table 2 above, collagen synthesis was significantly promoted in all of the examples, and the extract of fruit of miloparan (Example 1), keblagic acid (Example 2), gallic acid (Example 3) In addition, it can be seen that kebulinic acid (Example 4) has a higher collagen synthesis promoting effect than the reference example.
[0031] 実験例 3  [0031] Experimental Example 3
膚外用剤 (クリーム製剤)の調製例  Preparation example of external preparation for skin (cream preparation)
実験例 1で得られたミロバラン果実を使用し、下記表 3の処方(重量%)に従い、下 記の製造例に準拠し、ミロバラン果実エキス 0. 5%配合クリーム製剤(以下、「ミロバラ ン配合クリーム」 、う)を調製した。  Using the milobaran fruit obtained in Experimental Example 1 and following the formulation (% by weight) shown in Table 3 below, in accordance with the production example below, a cream formulation containing 0.5% milobaran fruit extract (hereinafter referred to as “Milobalan formulation”). A cream ", u) was prepared.
[0032] まず、流動パラフィン、パルミチン酸イソプロピル、ステアリン酸、セタノール、モノス テアリン酸グリセリン、ジメチルポリシロキサン、および一部のパラォキシ安息香酸エス テルを混合し、加熱した。次に、残りのパラォキシ安息香酸エステル、 1,3—ブチルダ リコール、ェデト酸ニナトリウム、トリエタノールァミン、精製水を混合し加熱し、先の混 合物に加え乳化させた。冷却後、フエノキシエタノール、ミロバラン果実エキスを添カロ することによりクリームを調製した。  [0032] First, liquid paraffin, isopropyl palmitate, stearic acid, cetanol, glyceryl monostearate, dimethylpolysiloxane, and some esters of paraoxybenzoate were mixed and heated. Next, the remaining paraoxybenzoic acid ester, 1,3-butyldaryl, disodium edetate, triethanolamine, and purified water were mixed and heated, and added to the previous mixture to emulsify. After cooling, a cream was prepared by adding phenoxyethanol and myrobalan fruit extract.
[0033] [表 3] 原料名 ミロバラン配合クリーム 基剤のみ [0033] [Table 3] Ingredient name Myrobalan cream combination Base only
流動パラフィン 10.0 10.0  Liquid paraffin 10.0 10.0
パルミチン酸イソプロピル 3.0 3.0  Isopropyl palmitate 3.0 3.0
ステアリン酸 4.5 4.5  Stearic acid 4.5 4.5
セタノール 3.0 3.0  Cetanol 3.0 3.0
モノステアリン酸グリセリン 3.5 3.5  Glycerol monostearate 3.5 3.5
ジメチルポリシロキサン 1.0 1.0  Dimethylpolysiloxane 1.0 1.0
/ ラオキシ安息香酸エステル 0.3 0.3  / Laoxybenzoic acid ester 0.3 0.3
1 ,3-ブチルグリコール 5.0 5.0  1,3-butyl glycol 5.0 5.0
ェデト酸ニナ卜リウム 0.05 0.05  Nedarium edetate 0.05 0.05
トリエタノールァミン 0.8 0.8  Triethanolamine 0.8 0.8
フエノキシエタノール 0.2 0.2  Phenoxyethanol 0.2 0.2
精製水 68.15 68.65  Purified water 68.15 68.65
ミロバラン果実エキス 0.5 - Myrobalan fruit extract 0.5-
100.0 100.0 100.0 100.0
[0034] 実験例 4 [0034] Experimental Example 4
人浴剤の調製例  Preparation example of human bath
下記表 4の処方(重量%)に従い、すべての原料を均一に混合することによりミロバ ラン果実エキス配合粉体入浴剤を調製した。  In accordance with the formulation (% by weight) shown in Table 4 below, a powder bath containing milobaran fruit extract was prepared by uniformly mixing all raw materials.
[0035] [表 4]  [0035] [Table 4]
Figure imgf000010_0001
Figure imgf000010_0001
[0036] 下記表 5の処方 (重量%)に従 1 ヽ、 A相および B相を 70°Cに加熱し完全溶解させ、 A相を B相に添加後、 30°Cまで冷却することによりミロバラン果実エキス配合液状入 浴剤を調製した。 [0036] According to the formulation (% by weight) shown in Table 5 below: 1 に よ り, Phase A and Phase B were heated to 70 ° C to completely dissolve, and after Phase A was added to Phase B, cooled to 30 ° C A liquid bath containing a myobalan fruit extract was prepared.
[0037] [表 5] 原料名 配合量 (重量 ) [0037] [Table 5] Raw material name Compounding amount (weight)
(A相)  (Phase A)
流動パラフィン 30.0  Liquid paraffin 30.0
コメヌ力油 10.0  Comenu oil 10.0
POEセチルェ一テル 2.5  POE Setilje 2.5
モノ/《ルミチン酸ソルビタン 2.5  Mono / << Sorbitan Luminate 2.5
フエノキシエタノール 0.3  Phenoxyethanol 0.3
香料 0.5  Fragrance 0.5
(B相)  (Phase B)
精製水 53.7  Purified water 53.7
ミロパラン果実エキス 0.3  Myloparan fruit extract 0.3
パラォキシ安息香酸メチル 0.2  Methyl paraoxybenzoate 0.2
100.0  100.0
[0038] 実験例 5 [0038] Experimental Example 5
化耕水の調製例  Preparation example of fossil water
下記表 6の処方(重量%)に従い、水相にアルコール相を添加し原液を調整し、そ の原液を缶に入れ、 LPG、ブタン等のガスを充填することによりミロパラン果実エキス 配合化粧水 (エアゾール製品)を調製した。  In accordance with the formulation (% by weight) shown in Table 6 below, the alcohol phase is added to the aqueous phase to prepare a stock solution, the stock solution is put into a can, and filled with a gas such as LPG or butane. Aerosol product) was prepared.
[0039] [表 6] [0039] [Table 6]
Figure imgf000011_0001
Figure imgf000011_0001
[0040] 下記表 7の処方(重量0 /0)に従い、水相にアルコール相を添カ卩し、可溶化させること により pH5. 5のミロバラン果実エキス配合弱酸性ィ匕粧水 (透明タイプ)を調製した。 [0040] Formulation of Table 7 in accordance with (wt 0/0), the alcohol phase was添Ka卩the aqueous phase, pH 5 by solubilizing. 5 Mirobaran fruit extract combination weakly acidic I匕粧water (transparent type) Was prepared.
[0041] [表 7] 原料名 配合置(重量%) [0041] [Table 7] Raw material name Compounding (wt%)
(水相)  (Water phase)
1 . 3—ブチレングリコール 5.0  1.3-Butylene glycol 5.0
グリセリン 5.0  Glycerin 5.0
ピロリドンカルボン酸ナトリウム 0.5  Sodium pyrrolidonecarboxylate 0.5
ヒアルロン酸ナトリウム 0.001  Sodium hyaluronate 0.001
ポリビニルピロリドン 0.1  Polyvinylpyrrolidone 0.1
クェン酸 微量  Quenic acid
精製水 残量  Purified water remaining
(アルコール相)  (Alcohol phase)
エタノール 10.0  Ethanol 10.0
POEォレイルエーテル 1.0  POE oleyl ether 1.0
ォレイルアルコール 0.1  Oleil alcohol 0.1
鲊酸トコフ: I:ロール 0.01  Tokovic oxalate: I: Roll 0.01
防腐剤 0.1  Preservative 0.1
香料 微量  Perfume
ミロバラン果実エキス 5.0  Myrobalan fruit extract 5.0
100.0  100.0
[0042] 下記表 8の処方(重量0 /0)に従い、水相にアルコール相を添カ卩し、乳化させることに より pH7. 5のミロバラン果実エキス配合化粧水(白濁タイプ)を調製した。 According [0042] Formulation of Table 8 (wt 0/0), the alcohol phase was添Ka卩the aqueous phase was prepared more pH 7. 5 Mirobaran fruit extract formulation lotion of (cloudy type) to be emulsified.
[0043] [表 8] [0043] [Table 8]
Figure imgf000012_0001
下記表 9の処方(重量0 /0)に従い、水相にアルコール相を添加して可溶ィ匕させた後 、粉体相を添加することにより PH6. 2の 3層型のミロバラン果実エキス配合化粧水( 分離型タイプ)を調製した。
Figure imgf000012_0001
According to the formulation shown in Table 9 (weight 0/0), After Ka溶I匕by adding alcohol phase in an aqueous phase, by adding a powder phase PH6. Mirobaran fruit extract combination of 3-layer type 2 A lotion (separate type) was prepared.
[0045] [表 9] 原料名 配合量 (重置%) [0045] [Table 9] Raw material name Compounding amount
(水相)  (Water phase)
1 . 2—へキサンジオール 3.0  1.2-Hexanediol 3.0
1 . 3—ブチレングリコール 5.0  1.3-Butylene glycol 5.0
マルチ! ^一ル 0.1  Multi! ^ One 0.1
ヒアルロン酸ナトリウム 0.05  Sodium hyaluronate 0.05
キサンタンガム 0.01  Xanthan gum 0.01
リンゴ酸 微量  Malic acid
精製水 残 5  Purified water remaining 5
(アルコール相)  (Alcohol phase)
エタノール 20.0  Ethanol 20.0
POEソルビタンモノラウリン酸エステル 0.1  POE sorbitan monolaurate 0.1
スクヮラン 3.0  Skullan 3.0
ホホノく油 0.5  Hohono oil 0.5
メントール 0.02  Menthol 0.02
カンファー 0.005  Camphor 0.005
防腐剤 0.1  Preservative 0.1
香料 微曼  Fragrance
ミロバラン果実エキス 1.0  Myrobalan fruit extract 1.0
(粉体相)  (Powder phase)
酸化鉄 (ベンガラ) 0.02  Iron oxide (Bengara) 0.02
酸化亜鉛 0.2  Zinc oxide 0.2
カオリン 1.0  Kaolin 1.0
タルク 2.0  Talc 2.0
100.0  100.0
[0046] 験例 6 [0046] Experiment 6
クリームの調製例  Example of cream preparation
下記表 10の処方 (重量%)に従い、油相と水相をそれぞれ 70°Cに加熱し、完全溶 解させた。水相に油相を添加して乳化させた後、冷却後、添加相を添加することによ り pH6. 1のミロパラン果実エキス配合ボディクリームを調製した。  According to the formulation (% by weight) shown in Table 10 below, the oil phase and the aqueous phase were each heated to 70 ° C for complete dissolution. The oil phase was added to the aqueous phase to emulsify, and after cooling, the added phase was added to prepare a body cream containing a myloparan fruit extract with pH 6.1.
[0047] [表 10] [0047] [Table 10]
原料名 配合量 (重量お) Raw material name Compounding amount (weight)
(油相)  (Oil phase)
セタノール 0.5  Cetanol 0.5
ワセリン 2.0  Vaseline 2.0
スクヮラン 10.0  Skulun 10.0
自己乳化型モノステアリン酸グリセリン 2.5  Self-emulsifying glyceryl monostearate 2.5
POEソルビタンモノステアリン酸エステル 1.5  POE sorbitan monostearate 1.5
ホホバ油 1.0  Jojoba oil 1.0
パント亍ニルェチルエーテル 0.05  Pantoyl ether ether 0.05
防腐剤 0.1  Preservative 0.1
(水相)  (Water phase)
プロピレングリコール 1.0  Propylene glycol 1.0
1 , 2—へキサンジオール 1.0  1,2-Hexanediol 1.0
グリセリン 0.5  Glycerin 0.5
モンモリロナイト 2.0  Montmorillonite 2.0
ベントナイト 0.5  Bentonite 0.5
カルボキシメチルセル口一ス 0.1  Carboxymethyl cell mouthpiece 0.1
防腐剤 0.2  Preservative 0.2
精製水 残量  Purified water remaining
(添加相)  (Additional phase)
香料 微量  Perfume
酒石酸 0.1  Tartaric acid 0.1
ミロパラン果実エキス 0.0001  Myloparan fruit extract 0.0001
100.0  100.0
[0048] 下記表 11の処方 (重量%)に従い、油相と水相をそれぞれ 70°Cに加熱し、完全溶 解させた。水相に油相を添加して乳化させた後、冷却後、添加相を添加することによ り pH7. 5のミロバラン果実エキス配合フェイスクリームを調製した。 [0048] According to the formulation (% by weight) shown in Table 11 below, the oil phase and the aqueous phase were each heated to 70 ° C for complete dissolution. An oil phase was added to the aqueous phase to emulsify, and after cooling, an additional phase was added to prepare a face cream with a myobalan fruit extract having a pH of 7.5.
[0049] [表 11] [0049] [Table 11]
原料名 配合置 (重量%) Raw material name Compounding (weight%)
(油相)  (Oil phase)
ステアリン酸 2.0  Stearic acid 2.0
ステアリルアルコール 3.0  Stearyl alcohol 3.0
脱臭ラノリン 2.0  Deodorized Lanolin 2.0
オリ一ブ油 15.0  Olive oil 15.0
モノステアリン酸グリセリン 2.0  Glycerol monostearate2.0
POEォレイルエーテル 2.0  POE oleyl ether 2.0
トリ(カブリル'カブリン酸)グリセリン 5.0  Tri (cabril 'cabric acid) glycerin 5.0
酢酸トコフ: cロール 0.05  Tokov acetate: c-roll 0.05
パルミチン酸レチノール 0.05  Retinol palmitate 0.05
防腐剤 0.1  Preservative 0.1
卜コフェローレ 0.05  卜 Coferre 0.05
(水相)  (Water phase)
1 , 3—ブチレングリコール 3.0  1,3-Butylene glycol 3.0
ソルビ! ル 1.0  Sorbi! Le 1.0
ジグリセリン 1.0  Diglycerin 1.0
キサンタンガム 0.25  Xanthan gum 0.25
カルボキシビ二ルポリマー 0.1  Carboxyvinyl polymer 0.1
水酸化カリウム 0.1  Potassium hydroxide 0.1
防腐剤 0.2  Preservative 0.2
精製水 残量  Purified water remaining
(添加相)  (Additional phase)
香料 微量  Perfume
ミロパラン果実エキス 0.001  Myloparan fruit extract 0.001
100.0  100.0
[0050] 下記表 12の処方 (重量%)に従い、油相と水相をそれぞれ 70°Cに加熱し、完全溶 解させた。水相に油相を添加して乳化させた後、冷却後、微細に粉砕した粉体相お よび添加相を添加することにより SPF20のミロバラン果実エキス配合日焼け止めタリ ームを調製した。 [0050] According to the formulation (% by weight) shown in Table 12 below, the oil phase and the aqueous phase were each heated to 70 ° C to be completely dissolved. An oil phase was added to the aqueous phase to emulsify, and after cooling, a finely pulverized powder phase and an additional phase were added to prepare a sunscreen tarm containing SPF20 milobaran fruit extract.
[0051] [表 12] [0051] [Table 12]
原料名 配合量 (重 Raw material name Compounding amount (heavy
(油相)  (Oil phase)
ステアリン酸 1.0  Stearic acid 1.0
セタノ一ル 3.0  Setanoir 3.0
シァ脂 4.0  Shea fat 4.0
ォリーブ油 10.0  Olive oil 10.0
モノステアリン酸 POEグリセリン 2.0  Monostearic acid POE glycerin 2.0
POEォレイルエーテル 1.0  POE oleyl ether 1.0
2—ェチルへキサン酸セチル 5.0  2-Ethylhexanoic acid cetyl 5.0
酢酸トコフエロール 0.05  Tocopherol acetate 0.05
パルミチン酸レチノール 0.05  Retinol palmitate 0.05
防腐剤 0.1  Preservative 0.1
天然ビタミン E 0.05  Natural vitamin E 0.05
パラメトキシケィ皮酸 2—ェチルへキシル 1.0  2-Methoxyhexyl p-methoxycinnamate 1.0
ォキシベンゾン 0.5  Oxybenzone 0.5
(水相)  (Water phase)
1 , 2—ペンタンジオール 3.0  1,2-pentanediol 3.0
ソルビ! ^一ル 2.0  Sorbi! ^ One 2.0
グリセリン 0.5  Glycerin 0.5
キサンタンガム 0.8  Xanthan gum 0.8
防腐剤 0.2  Preservative 0.2
精製水 残量  Purified water remaining
(粉体相)  (Powder phase)
酸化チタン 12.0  Titanium oxide 12.0
酸化亜鉛 0.5  Zinc oxide 0.5
ベンガラ 0.001  Bengala 0.001
酸化チタン ·無水ケィ酸複合物 2.0  Titanium oxide · Keyed anhydride composite 2.0
(添加相)  (Additional phase)
香料 微量  Perfume
ミロバラン果実エキス 0.01  Myrobalan fruit extract 0.01
100.0 実験例 7  100.0 Experimental Example 7
トニックの讕製例 Example of smoked tonic
下記表 13の処方(重量0ん)に従い、まず、酢酸 dl— a トコフエロール、イソプロピ ルメチルフエノール、パントテュルアルコール、グリチルレチン酸、エタノール(99. 5 %)、ミリスチン酸オタチルドデシル、 2—ェチルヘンサン酸ォクチル、香料、メントー ルを均一に混合した。次に、センプリエキス (抽出液)、ニンジンエキス (抽出液)、 1, 3—ブチレングリコール、ジプロピレングリコール、ァスコルビン酸リン酸エステルナトリ ゥム、ェデト酸 4ナトリウム、ポリオキシエチレン硬化ヒマシ油(50E.O)、ポリオキシェ チレン硬化ヒマシ油(20E.O)、ミロバラン果実エキス、精製水を均一に混合した。最 後に両者を混合し、濾過して充填することによりミロバラン果実エキス配合液状型トニ ックを調製した。 [0053] [表 13] In accordance with the formulation shown in Table 13 below ( zero weight), first, dl-a tocopherol acetate, isopropylmethylphenol, pantothel alcohol, glycyrrhetinic acid, ethanol (99.5%), octyldodecyl myristate, 2-ethylhensanic acid Octyl, fragrance, and menthol were mixed uniformly. Next, sempri extract (extract), carrot extract (extract), 1,3-butylene glycol, dipropylene glycol, sodium ascorbate phosphate, sodium edetate, polyoxyethylene hydrogenated castor oil ( 50E.O), polyoxyethylene hydrogenated castor oil (20E.O), myrobalan fruit extract, and purified water were mixed uniformly. Finally, both were mixed, filtered and filled to prepare a liquid type tonic containing milobaran fruit extract. [0053] [Table 13]
Figure imgf000017_0001
Figure imgf000017_0001
[0054] 下記表 14の処方(重量%)に従 、、まず、酢酸 dl— a トコフ ロール、イソプロピ ルメチルフエノール、パントテュルアルコール、エタノール(99. 5%)、香料、メントー ルを均一に混合した。次に、センプリエキス (抽出液)、ニンジンエキス (抽出液)、ジ プロピレングリコール、 3—メチルー 1, 3 ブタンジオール、ァスコノレビン酸リン酸エス テルナトリウム、ェデト酸 4ナトリウム、ポリオキシエチレンポリオキシプロピレングリコー ル、モノラウリン酸デカグリセリル、ミロバラン果実エキス、精製水を均一に混合した。 次に両者を混合し、濾過して原液とし、最後に、原液と噴射剤を充填処方に合わせ て、缶に充填することによりミロバラン果実エキス配合エアゾール型トニックを調製し た。  [0054] According to the formulation (% by weight) shown in Table 14 below, first, dl-a tocolol acetate, isopropylmethylphenol, pantol alcohol, ethanol (99.5%), flavor, and menthol were mixed uniformly. did. Next, sempri extract (extract), carrot extract (extract), dipropylene glycol, 3-methyl-1,3-butanediol, asconolevic acid ester sodium phosphate, edetate tetrasodium, polyoxyethylene polyoxypropylene Glycol, decaglyceryl monolaurate, myrobalan fruit extract, and purified water were mixed uniformly. Next, both were mixed and filtered to obtain a stock solution. Finally, the stock solution and propellant were matched to the filling formulation and filled into cans to prepare an aerosol-type tonic containing milobaran fruit extract.
[0055] [表 14] 原料名 配合量(重置%) [0055] [Table 14] Raw material name Compounding amount
(原液)  (Undiluted solution)
醉酸 d卜 a -卜コフェロー ^ (レ 0.1  Succinic acid d 卜 a-卜 Cofero ^ (Le 0.1
センブリエキス (抽出液) 1.0  Assembly extract (extract) 1.0
イソプロピルメチルフエノール 0.1  Isopropylmethylphenol 0.1
パントテニルアルコール 0.5  Pantothenyl alcohol 0.5
ニンジンエキス (抽出液) 1.0  Carrot extract (extract) 1.0
エタノール(99.5%) 10.0  Ethanol (99.5%) 10.0
ジプロピレングリコール 3.0  Dipropylene glycol 3.0
3-メチル -1. 3-ブタンジオール 5.0  3-methyl-1.3-butanediol 5.0
ァスコルビン酸リン酸エステルナトリウム 0.1  Ascorbic acid sodium phosphate 0.1
ェデト酸 4ナトリウム 0.1  Edetic acid 4sodium 0.1
ポリオキシエチレンポリオキシプロピレングリコール 3.0  Polyoxyethylene polyoxypropylene glycol 3.0
モノラウリン酸デカグリセリル 0.5  Decaglyceryl monolaurate 0.5
香料 0.3  Fragrance 0.3
メントール 0.3  Menthol 0.3
ミロバラン果実エキス 0.5  Myrobalan fruit extract 0.5
精製水 残量  Purified water remaining
100.0  100.0
(噴射剤)  (Propellant)
DME 70.0  DME 70.0
し PG 30.0  PG 30.0
100.0  100.0
(充填処方)  (Filling prescription)
原液 80.0  Stock solution 80.0
噴射剤 20.0  Propellant 20.0
100.0  100.0
[0056] 実験例 8 [0056] Experimental Example 8
皮膚外用剤 しての;商用例  As a topical skin preparation; commercial example
実験例 3にて得られたミロバラン果実エキス 0. 5%配合クリーム製剤および比較例 として基剤のみをそれぞれ、 30歳女性の左右の手背(手の甲)に 1日 3回、大豆大程 度を塗布し、塗布前と 1ヶ月間後の肌のツヤ、ハリ、柔軟性、カサカサ感、くすみ感、 キメおよびシヮを下記の評価基準に従い評価した。  Milobaran fruit extract obtained in Experimental Example 3 0.5% cream formulation and as a comparative example, only the base was applied to the left and right hand (back of hand) of a 30-year-old woman three times a day, about 30% In addition, the skin gloss, firmness, softness, crispness, dullness, texture and wrinkle before and after application for 1 month were evaluated according to the following evaluation criteria.
[0057] (評価基準) [0057] (Evaluation criteria)
ツヤ、ハリ、柔軟性:「ない(1)、あまりない(2)、どちらともいえない(3)、ややある(4) Shiny, firm, flexible: “No (1), not very much (2), neither can be said (3), some (4)
、ある(5)」 There is (5) "
カサカサ感:「カサカサする(1)、ややカサカサする(2)、どちらとも 、えな 、(3)、や やしつとりする(4)、しっとりする(5)」  A feeling of rustling: “Crispy (1), Slightly rustling (2), Both, Ena (3), Slightly moist (4), Moist (5)”
くすみ感:「ある(1)、ややある (2)、どちらとも!ヽえな 、 (3)、あまりな!/、 (4)、 ¾ ヽ (5) J キメ:「あら ヽ(1)、ややあら 、 (2)、どちらともレ、えな 、 (3)、やや細か!/、 (4)、細か!/、 ( 5)」 Dullness: “There is (1), some (2), both! Fearless, (3), Much! /, (4), ¾ ヽ (5) J Kime: “Ah ヽ (1), Ah, Ah, (2), both of them, Ena, (3), Slightly fine!
シヮ:「目立つ(1)、やや目立つ(2)、どちらとも 、えな ヽ(3)、あまり目立たな ヽ (4)、 目立たない(5)」  Shio: “Essential (1), Slightly outstanding (2), both are Ena (3), Less prominent (4), Inconspicuous (5)”
評価結果を下記表 15に示す。  The evaluation results are shown in Table 15 below.
[表 15]  [Table 15]
Figure imgf000019_0001
Figure imgf000019_0001
[0059] 上記表 15より、塗布前および基剤のみの塗布と比較して明らかなように、ミロバラン 果実の抽出物は、ツヤ、ハリ、柔軟性、カサカサ感、くすみ感、キメおよびシヮのいず れの項目において良好な効果を示すことがわ力つた。  [0059] From Table 15 above, it is clear that the extract of milobaran fruit is glossy, firm, soft, crisp, dull, textured, and wrinkled It was very effective to show good effects in all items.
[0060] また、 1ヶ月塗布後の顕微鏡写真による結果を図 1に示す。(a)はミロバラン果実ェ キスを含有する皮膚外用剤を塗布した場合、 (b)は基剤のみを塗布した場合である。 写真からも、基剤のみと比較して、ミロバラン果実エキスを含有する皮膚外用剤を使 用した場合には、キメが細力べ整っていることが分かる。また、保湿力およびハリが向 上し、くすみがなくなった。  [0060] Fig. 1 shows the results of micrographs after application for 1 month. (A) shows the case where a topical skin preparation containing milobalan fruit juice is applied, and (b) shows the case where only the base is applied. From the photograph, it can be seen that the texture is better when using a topical skin preparation containing a milobaran fruit extract compared to the base alone. In addition, moisturizing power and elasticity improved, and dullness disappeared.

Claims

請求の範囲 The scope of the claims
[1] ミロバランの果実の抽出物を有効成分とすることを特徴とするコラーゲン合成促進 剤。  [1] A collagen synthesis promoter characterized by comprising an extract of myrobalan fruit as an active ingredient.
[2] 皮膚外用剤である請求項 1記載のコラーゲン合成促進剤。  [2] The collagen synthesis promoter according to claim 1, which is an external preparation for skin.
[3] 肌質改善剤である請求項 1記載のコラーゲン合成促進剤。 [3] The collagen synthesis promoter according to claim 1, which is a skin quality improving agent.
[4] ケブラグ酸、ケブリン酸、没食子酸およびコリラギン力 なる群力 選択される 1種ま たは 2種以上を有効成分とすることを特徴とするコラーゲン合成促進剤。  [4] A collagen synthesis promoter characterized by comprising one or more selected active ingredients as keblagic acid, kebric acid, gallic acid, and collilaginity.
[5] 皮膚外用剤である請求項 4記載のコラーゲン合成促進剤。 [5] The collagen synthesis promoter according to claim 4, which is an external preparation for skin.
[6] 肌質改善剤である請求項 4記載のコラーゲン合成促進剤。 [6] The collagen synthesis promoter according to claim 4, which is a skin quality improving agent.
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JP2008143784A (en) * 2006-12-06 2008-06-26 B & C Laboratories Inc Cell growth promoter
JP2009256269A (en) * 2008-04-18 2009-11-05 Tsumura Lifescience Co Ltd Profilaggrin and/or filaggrin production accelerator
KR101483440B1 (en) * 2008-05-02 2015-01-19 (주)아모레퍼시픽 Medicinal plants extract using processing of herbal medicine and composition of skin external application comprising the same
JPWO2011061932A1 (en) 2009-11-18 2013-04-04 株式会社ロッテ Ceramide and collagen synthesis promoter and collagen saccharification inhibitor
JP7075298B2 (en) * 2018-07-05 2022-05-25 株式会社ノエビア External skin preparation

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