JP2006265120A - Collagen synthesis accelerator - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a collagen synthesis accelerator having sufficient collagen synthesis accelerating action and high skin balancing effect. <P>SOLUTION: The invention provides a collagen synthesis accelerator containing the extract of Terminalia chebula fruit as an active component and a collagen synthesis accelerator containing one or more components selected from chebulagic acid, chebulinic acid, gallic acid and corilagin as active components. The collagen synthesis accelerator is suitable as an external medicine for skin and a skin balance improving agent to impart the skin with moistness and springiness, improve the skin texture and keep the moisture-retention of the skin. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a collagen synthesis promoter, and more particularly, to a collagen synthesis promoter intended to promote collagen synthesis of fibroblasts, to give freshness and firmness to the skin, and to retain the water retaining ability of the epidermis.

  Collagen is a major protein that constitutes the connective tissue of animals, and collagen occupies nearly 30% of the total protein of the human body. In the skin, collagen has a function of imparting freshness and firmness of 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 of the skin, the moisturizing power, etc. decline, leading to aging phenomena such as wrinkles and sagging.

  These include skin relaxation and elasticity due to a decrease in the number of cells producing extracellular matrix of the dermis, a decrease in cell function such as a decrease in cell division rate, a decrease and degeneration of collagen fibers, a decrease in subcutaneous adipose tissue, etc. Occurs due to the loss of power.

  Collagen in particular is known to play an important role in the suppression and recovery of skin aging, and for the purpose of improving skin aging, a composition containing collagen or a substance that promotes the synthesis of collagen is used. The method of apply | coating the containing composition to skin is performed.

  As substances that promote collagen synthesis, ascorbic acid phosphate, retinoic acid and the like are known. Ascorbic acid phosphate is a kind of ascorbic acid derivative and is converted into vitamin C by being absorbed through the skin. Vitamin C not only activates collagen synthesis, but also matures an intercellular substance (extracellular matrix) having a collagen skeleton, and is one of the cell growth factors that induce cell tissue formation. 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, and is the main body of physiological activity of vitamin A in the body itself. In the US, it is approved by the FDA (Food and Drug Administration) as a therapeutic drug for wrinkles and acne.

Furthermore, Non-Patent Document 2 reports that the alcohol extract of leaves of milobaran (Terminalia chebula) has an effect on wound healing, and epithelialization is significant in in vivo tests using rats. And a significant increase in protein, DNA and collagen components in the granulation tissue was observed. In addition, it has been reported that keblagic acid, kebric acid, corilagin, and gallic acid have been isolated from the leaves of myrobalan (see Non-Patent Document 3).
Eur. J. Biochem, 174, p231 (1988) Phytother.Res, 16, p227 (2002) Bull.Central Leather Res.Inst., 8, p230 (1961)

  The method of applying collagen to the skin surface in order to supply collagen to the skin did not essentially improve the skin function because collagen has a polymer structure and is not absorbed by the barrier function of the epidermis. Further, collagen synthesis promoting substances such as retinoic acid are not sufficiently satisfactory in terms of effects, and further improvement is desired.

  Accordingly, an object of the present invention is to provide a collagen synthesis accelerator having a sufficient collagen synthesis promoting action and a high skin conditioning effect.

  As a result of diligent studies to solve the above-mentioned problems, the present inventor found that the fruit (coconut) of Myrobalan (Terminalia chebula) contains a component having a high collagen promoting action, and completed the present invention. It came. That is, the collagen synthesis promoter of the present invention is characterized by comprising an active ingredient of a fruit extract of milobaran (hereinafter also referred to as “mylobaran fruit extract”). As described above, it is known that the alcohol extract of milobaran leaves has a wound healing effect and significantly increases the collagen component in the granulation tissue. It was not known to have a better effect. In addition, regarding the degree of the collagen synthesis promoting action of myrobalan leaves, details are unknown and it is difficult to obtain. Furthermore, it was not known as to which substances among the substances contained in the extract of the leaves of Milobaran contributed more to collagen synthesis.

  The other collagen synthesis promoter of the present invention comprises one or more selected from the group consisting of chebulagic acid, chebulinic acid, gallic acid and corilagin. It is an active ingredient.

  Furthermore, the collagen synthesis promoter of the present invention can be suitably used as a skin external preparation, and can be suitably used as a skin quality improving agent for use.

  Collagen synthesis can be effectively promoted by the collagen synthesis promoter of the present invention. In addition, when the collagen synthesis promoter of the present invention is used as an external preparation for skin, it is possible to impart freshness and firmness to the skin, to adjust the texture, and to maintain the water retaining ability of the epidermis.

  Hereinafter, a preferred embodiment of the present invention will be specifically described. The collagen synthesis accelerator according to the present invention is obtained by using a milobaran fruit extract as an active ingredient, but the milobaran fruit extract can be obtained by a conventional method, for example, after immersing or heating and refluxing a milobaran fruit with an extraction solvent, The extract obtained by filtration 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 selected from them, or two or more types arbitrarily combined can be used. Extraction conditions are not particularly limited. For example, with respect to 1 part by weight of milobaran fruit, 2 to 100 parts by weight of solvent, and the temperature and time at the time of extraction are 0 to 100 ° C. for 10 minutes to 1 week. It can be.

  In addition, another 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 the components of myrobalan fruit extract. However, keblagic acid and kebric acid that exhibit a high collagen synthesis promoting action and have a high content are preferable. Each component can be obtained by extraction and isolation from a plant, or synthesis by a known method. By extracting the milobaran fruit extract from the milobaran fruit by the above method and then isolating it, each can be suitably obtained. 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.

  When the collagen synthesis promoter of the present invention is used as an external preparation for skin, the compounding amount of milobalan fruit extract and the components of keblagic acid, kebric acid, gallic acid and corilagin, which are the components of myrobalan fruit extract, is the kind of active ingredient, agent Usually, the total amount is preferably 0.0001 to 5%, more preferably 0.001 to 0.1% as a dry weight in the total amount of the external preparation, although it varies depending on the type. Below this range, the effect of promoting collagen synthesis is hard to be fully exerted, and if it exceeds this range, the effect cannot be expected to increase, and it is not economical, and also has stickiness, a unique smell of herbal medicine, reduced feeling of use, herbal medicine This is not preferable because of problems such as dyeing.

  In addition to the above-mentioned myrobalan fruit extract, the external preparation for skin of the present invention, within the range not impairing the effects of the present invention, other components usually used for external skin preparations such as cosmetics and pharmaceuticals, for example, humectants, Oily ingredients, surfactants, vitamins, proteolytic enzymes, thickeners, preservatives, powders, antioxidants, UV absorbers, emulsifiers, alcohols, colorants, aqueous ingredients, water, various skin nutrients, etc. Can be appropriately blended as necessary.

  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, hyaluronic acid salts, chondroitin sulfate, chitosan, and the like. Molecule, urea, sodium lactate, pyrrolidone carboxylate and the like.

  Examples of oil components include soybean oil, nutka oil, avocado oil, almond oil, olive oil, cacao butter, sesame oil, persic oil, castor oil, coconut oil, mink oil, beef tallow, pork fat, and other natural fats and oils. Hardened oil obtained by hydrogenation of fats and oils, synthetic glycerides such as myristic acid glyceride and 2-ethylhexanoic acid glyceride, fats and oils such as diglyceride, jojoba oil, carnauba wax, whale wax, beeswax, lanolin wax, liquid paraffin , Hydrocarbons such as petrolatum, paraffin, microcrystalline wax, ceresin, squalane, pristane, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, lanolinic acid, isostearic acid, etc. Higher fatty acids, lauryl alcohol, cetyl al , Stearyl alcohol, oleyl alcohol, cholesterol, 2-hexyldecanol, jojoba alcohol and other higher alcohols, cetyl octoate, myristyl lactate, cetyl lactate, myristyl myristate, octyldodecyl myristate, isopropyl myristate, isopropyl palmitate, Examples include esters such as isopropyl adipate, butyl stearate, decyl oleate, cholesterol isostearate, essential oils, and silicone oils.

  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 sorbitol, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether , Polyoxyethylene alkylphenyl ether, polyoxyethylene fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene castor oil, polyglycerin fatty acid ester, fatty acid monoglyceride, sucrose fatty acid ester, higher fatty acid alkanolamide and other nonionic surfactants , Sodium α-olefin sulfonate, sodium lauryl sulfate, sodium cetyl sulfate, polyoxye Sodium lauryl sulfate, disodium lauryl sulfosuccinate, linear alkylbenzene sulfonate, branched alkylbenzene sulfonate, alkyl sulfate, alkenyl sulfate, alkyl ether carboxylate or alkenyl ether added with ethylene oxide and / or propylene oxide Anionic surfactants such as carboxylate, α-sulfo fatty acid ester, amino acid type surfactant, phosphate ester type surfactant, taurine type surfactant, amide ether sulfate type surfactant, carboxybetaine type, Examples include amphoteric surfactants such as aminocarboxylic acid and sulfobetaine type and cationic surfactants such as quaternary ammonium salts. Nonionic surfactants are particularly preferred from the viewpoint of safety.

  Examples of vitamins include vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin F, vitamin K, vitamin P, vitamin U, carnitine, ferulic acid, γ-oryzanol, lipoic acid, orotic acid and the like Derivatives and the like. Examples of the proteolytic enzyme include pepsin, trypsin, chymotrypsin, cathepsin, papain, bromelain, ficin, bacteria, yeast, and mold-derived protease.

  Examples of the thickener include water-soluble polymer compounds such as carboxyvinyl polymer, carboxymethyl cellulose, polyvinyl alcohol, carrageenan, gelatin, xanthan gum and polyacrylate, and inorganic salts such as sodium chloride and potassium chloride. Examples of the preservative include phenoxyethanol, methyl paraben, ethyl paraben, butyl paraben, sodium benzoate and the like. Examples of the powder include talc, sericite, mica, kaolin, silica, bentonite, vermiculite, zinc white, mica, mica titanium, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, bengara, iron oxide, ultramarine and the like. It is done. Examples of other components include fragrances, pigments, and bactericides.

  Moreover, the dosage form of the external preparation for skin of this invention is arbitrary, For example, it can be set as a lotion, an emulsion, a cream, an ointment, a dispersion liquid, a gel form, an aerosol, a pack, a bath agent etc.

Hereinafter, the present invention will be described in detail according to examples.
Experimental example 1
Preparation Example of Myrobalan Fruit Extract 20 ml of 30% ethanol was added to 20 g of fruit (dried product) of Myrobalan and 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, insoluble substances were filtered off from 50.28 g of myrobalan fruit extract obtained by room temperature extraction with 60% acetone, then Sephadex LH-20 (Pharmacia), MCI gel CHP20P (Mitsubishi Chemical Co., Ltd.) As a result of separation and purification by subjecting to various column chromatography using cellulose, cellulose, and ODS gel, kerabic acid, gallic acid, kebulic acid, chebulanin and corilagin were obtained in the yields shown in Table 1 below.

Experimental example 2
Collagen synthesis promotion action confirmation test Human fibroblasts (Detroit551) in a MEM medium containing 10% FBS, 1% NEAA, 1 mmol / L sodium pyruvate under conditions of 37 ° C. and 5% CO ₂ -95% air. ) Was cultured. Next, cells were collected by trypsin treatment, adjusted to 2 × 10 ⁵ cells / mL, and seeded at 100 μL each in a 96-well microplate. 37 ° C., after overnight incubation under conditions of 5% CO ₂ -95% air, and replaced with 0.5% FBS MEM medium containing the sample (150μL), 37 ℃, of 5% CO ₂ -95% air Cultivation was performed under conditions for 3 days. In addition, as for the sample, the sample contains milobaran fruit extract (Example 1), keblagic acid (Example 2), gallic acid (Example 3), and kevulinic acid (Example 4), which are the main components of the milobaran fruit extract. And corilagin (Example 5), quebrin as a comparative example, L-ascorbic acid-2-phosphate Mg salt (APM), which is conventionally known to have a collagen synthesis promoting action as a reference example, retinoic acid, Each sample was adjusted to a concentration of 25, 50 and 100 ppm and used.

After culture, 90 μL of the culture supernatant was transferred to an ELISA plate, and the amount of collagen synthesis was measured by an ELISA method using an anti-human collagen type 1 antibody. For the quantification, a calibration curve using human collagen type 1 as a standard was used. 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.

  From Table 2 above, collagen synthesis was significantly promoted in all of the examples, and the extract of fruit of milobaran (Example 1), keblagic acid (Example 2), gallic acid (Example 3) and kevulinic acid (implemented) It can be seen that Example 4) has a higher collagen synthesis promoting action than the Reference Example.

Experimental example 3
Preparation example of external preparation for skin (cream preparation) Using the milobaran fruit obtained in Experimental Example 1, in accordance with the prescription (weight%) of Table 3 below, based on the following production example, containing 0.5% of milobaran fruit extract A cream formulation (hereinafter referred to as “mylobalan-containing cream”) was prepared.

  First, liquid paraffin, isopropyl palmitate, stearic acid, cetanol, glyceryl monostearate, dimethylpolysiloxane, and some paraoxybenzoates were mixed and heated. Next, the remaining paraoxybenzoic acid ester, 1,3-butyl glycol, 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.

Experimental Example 4
Preparation example of bathing agent According to the formulation (% by weight) shown in Table 4 below, a powder bathing agent containing milobaran fruit extract was prepared by uniformly mixing all raw materials.

  In accordance with the formulation (% by weight) shown in Table 5 below, the A and B phases were heated to 70 ° C. to completely dissolve them, and after adding the A phase to the B phase, cooling to 30 ° C. Prepared.

Experimental Example 5
Preparation example of skin lotion According to the formulation (% by weight) shown in Table 6 below, the alcoholic phase is added to the aqueous phase to prepare a stock solution, the stock solution is placed in a can, and filled with a gas such as LPG or butane to extract a milobaran fruit extract. A formulated lotion (aerosol product) was prepared.

  According to the formulation (% by weight) shown in Table 7 below, an alcohol phase was added to the aqueous phase and solubilized to prepare a weakly acidic lotion (transparent type) containing a myobalan fruit extract having a pH of 5.5.

  According to the formulation (% by weight) shown in Table 8 below, an alcohol phase was added to the aqueous phase and emulsified to prepare a myobalan fruit extract-containing lotion (white turbid type) having a pH of 7.5.

  In accordance with the formulation (% by weight) shown in Table 9 below, the aqueous phase was solubilized by adding the alcohol phase, and then the powder phase was added to the skin lotion containing the three-layered milobalan fruit extract pH 6.2. Mold type) was prepared.

Experimental Example 6
Preparation Example of Cream According to the formulation (% by weight) shown in Table 10 below, the oil phase and the aqueous phase were each heated to 70 ° C. and completely dissolved. After 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 myobalan fruit extract with pH 6.1.

  According to the formulation (% by weight) shown in Table 11 below, the oil phase and the aqueous phase were each heated to 70 ° C. and completely dissolved. An oil phase was added to the aqueous phase to emulsify, and after cooling, an additional phase was added to prepare a face cream blended with a milobaran fruit extract having a pH of 7.5.

  According to the formulation (% by weight) shown in Table 12 below, the oil phase and the aqueous phase were each heated to 70 ° C. and 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 cream containing SPF20 milobaran fruit extract.

Experimental Example 7
Preparation example of tonic According to the formulation (% by weight) shown in Table 13 below, first, dl-α-tocopherol acetate, isopropylmethylphenol, pantothenyl alcohol, glycyrrhetinic acid, ethanol (99.5%), octyl myristate Dodecyl, octyl 2-ethylhensanate, flavor, and menthol were mixed uniformly. Next, assembly extract (extract), carrot extract (extract), 1,3-butylene glycol, dipropylene glycol, sodium ascorbate phosphate, sodium edetate, polyoxyethylene hydrogenated castor oil (50 EO ), 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.

  In accordance with the formulation (% by weight) shown in Table 14 below, first, dl-α-tocopherol acetate, isopropylmethylphenol, pantothenyl alcohol, ethanol (99.5%), flavor, and menthol were uniformly mixed. Next, assembly extract (extract), carrot extract (extract), dipropylene glycol, 3-methyl-1,3-butanediol, sodium ascorbate phosphate, tetrasodium edetate, polyoxyethylene polyoxypropylene Glycol, decaglyceryl monolaurate, myrobalan fruit extract, and purified water were mixed uniformly. Next, both were mixed, filtered to obtain a stock solution, and finally, the stock solution and propellant were matched to the filling formulation and filled into cans to prepare an aerosol tonic containing milobaran fruit extract.

Experimental Example 8
Example of application as a skin external preparation Three times a day for the cream preparation containing 0.5% of milobaran fruit extract obtained in Experimental Example 3 and the base as a comparative example, respectively, on the left and right hand back (back of hand) of 30-year-old woman A large amount of soybean was applied, and the gloss, firmness, softness, rustiness, dullness, texture and wrinkle of the skin before and after one month were evaluated according to the following evaluation criteria.

(Evaluation criteria)
Gloss, elasticity, flexibility: “No (1), not much (2), neither can be said (3), some (4), some (5)”
A feeling of rustling: “Crusting (1), Slightly rustling (2), Neither (3), Slightly moist (4), Moist (5)”
Dullness: “Yes (1), Somewhat (2), Neither (3), Not much (4), No (5)”
Kime: “Arai (1), A little Arrai (2), Neither (3), A little fine (4), A little (5)”
Wrinkle: “Conspicuous (1), Slightly conspicuous (2), Neither (3), Not conspicuous (4), Inconspicuous (5)”
The evaluation results are shown in Table 15 below.

  From Table 15 above, as is clear before application and compared with the application of the base alone, the extract of milobaran fruit is in any of the items of gloss, firmness, flexibility, crispness, dullness, texture and wrinkles. It was found to show a good effect.

  Moreover, the result by the micrograph after 1-month application | coating is shown in FIG. (A) is a case where the skin external preparation containing a milobaran fruit extract is applied, (b) is a case where only the base is applied. From the photograph, it can be seen that the texture is finely prepared when the skin external preparation containing the milobaran fruit extract is used as compared with the base alone. In addition, moisturizing power and elasticity improved, and dullness disappeared.

(A) The skin at the time of using the skin external preparation containing a milobaran fruit extract, (b) is the microscope picture of the skin at the time of apply | coating only a base.

Claims (4)

  A collagen synthesis promoter characterized by comprising an extract of a fruit of Myrobalan as an active ingredient.   A collagen synthesis promoter characterized by comprising one or more selected from the group consisting of keblagic acid, kebric acid, gallic acid and corilagin as active ingredients.   The collagen synthesis promoter according to claim 1 or 2, which is an external preparation for skin. It is a skin quality improving agent, The collagen synthesis promoter as described in any one of Claims 1-3.

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