JP2009256269A - Profilaggrin and/or filaggrin production accelerator - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a profilaggrin and/or filaggrin production accelerator which exhibits sufficient profilaggrin and/or filaggrin production acceleration and has a high skin preparation effect. <P>SOLUTION: The profilaggrin and/or filaggrin production accelerator has an extract of Terminalia chebula fruit as an active ingredient. The profilaggrin and/or filaggrin production accelerator has a chebulanin (at least one kind selected from the group consisting of chebulagic acid, chebulinic acid, and chebulanin) or its salt as an active ingredient. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a profilagrin and / or a filaggrin production promoter, and in particular, promotes the production of filaggrin, which is a base of a natural moisturizing factor that is largely involved in skin moisturizing, and retains sufficient natural moisturizing factor in the skin. The present invention relates to a profilagrin and / or filaggrin production promoter for preventing rough skin and dry skin.

  The skin consists of the epidermis and dermis, and the epidermis present on the surface prevents the evaporation of moisture and the invasion of foreign matter. However, internal factors such as aging, and external factors such as extreme low humidity environments such as wintertime, etc., caused the skin to dry, which caused rough skin and wrinkles.

  There are various causes for the dryness of the skin, one of which is a decrease in natural moisturizing factor (hereinafter also referred to as “NMF”) present in the epidermis. NMF includes amino acids, pyrrolidone carboxylic acid (and its salt), urea, mineral salts and organic acid (and its salt), etc. (Non-patent Document 1), and the decrease in these cannot maintain moisture in the skin. , The skin is dry.

  Therefore, as a conventional technique for preventing drying due to a decrease in NMF, it is known to apply a free amino acid, an amino acid metabolite, or an oil agent constituting NMF.

  In recent years, profilagrin and filaggrin have attracted attention as a factor of dry skin. Profilagrin is a huge phosphorylated protein that contains multiple filaggrin sequences, is synthesized in granule cells and accumulates in keratohyalin granules, but dephosphorylates and proteolyses when it changes into keratinocytes. It is a precursor of filaggrin biosynthesis that changes into filaggrin molecules upon receipt (Non-patent Document 2). On the other hand, filaggrin is a kind of basic protein produced in epidermal granule cells, has a molecular weight of about 40 kDa (Non-patent Document 1), functions to aggregate keratin fibers, forms compact keratinocytes, Furthermore, the upper layer of the stratum corneum is decomposed to become amino acids and derivatives thereof, and also functions as NMF. In addition, in ichthyosis vulgaris, a hereditary keratosis disorder, the expression of filaggrin is markedly reduced, resulting in a decrease in keratohyaline granules, a decrease in amino acids in the stratum corneum, a decrease in stratum corneum water content, It is known to show abnormalities such as scaling (Non-Patent Document 2).

  Furthermore, Non-Patent Document 3 reports that the alcohol extract of leaves of milobaran (Terminalia chebula) has an effect on wound healing, and epithelialization is significant in an in vivo test using rats. It was shown that significant increases in protein, DNA and collagen components in the granulation tissue were observed. In addition, it has been reported that keblagic acid, kevulinic acid, corilagin, and gallic acid were isolated from the leaves of myrobalan (see Non-patent Document 4).

Furthermore, Patent Document 1 discloses that an alcoholic extract of myrobalan fruit has an effect of promoting collagen synthesis.
JP 2006-265120 A Cosmetic Dictionary, p614, 716 (2003) Dermatology, p34 (2006) Phytother.Res, 16, p227 (2002) Bull.CentralLeather Res.Inst., 8, p230 (1961)

  The method of applying free amino acids, amino acid metabolites, or oils can prevent evaporation of moisture in the stratum corneum by covering the surface of the skin, but the effect cannot be expected to be sustained.

  In addition, if the production of profilagrin and / or filaggrin can be promoted, the decrease in NMF component can be eliminated permanently and the skin can be prevented from drying, but it still has a sufficient profilaggrin and / or filaggrin production promoting effect. Is not obtained.

  Furthermore, although it is known that the alcoholic extract of myrobalan fruit has a collagen synthesis promoting effect, there is no known profilaggrin and / or filaggrin production promoting effect with different actions and functions. Was unknown.

  Then, the objective of this invention is providing the profilaggrin and / or a filaggrin production promoter which exhibits sufficient profilaggrin and / or filaggrin production promotion effect, and has a high skin conditioning effect.

  As a result of intensive studies to solve the above-mentioned problems, the present inventor has produced profilagrin and / or filaggrin, in which an extract of fruit (coconut) of milobaran (Terminalia chebula) is present in the epidermis and forms the basis of NMF. Direct activation of functional cells enhances the original function of the skin, and profilagrin and / or filaggrin production promoting action is recognized in the components that are abundantly contained in the extract of fruit (coconut) of milobaran (Terminaliachebula) And found that their active ingredients have a common structure. That is, by increasing the amount of profilagrin and / or filaggrin, NMF can be increased, sufficient NMF can be secured in the stratum corneum, dry skin can be solved from the inside, and moisturized skin can be maintained. The inventors have found a material that can be obtained and have completed the present invention.

  The profilagrin and / or filaggrin production promoter of the present invention is characterized by containing an extract of a fruit of milobalan (hereinafter referred to as “mylobalan fruit extract”) as an active ingredient.

（式中、Ｒ^１及びＲ^２は、各々独立して、水素原子又は置換基を有してもよく分岐を有していてもよい炭素原子数３〜２０のアシル基を表し、Ｒ^１とＲ^２が連結して環状基を形成してもよい）で表される骨格を有するケブラニン類またはその塩を有効成分とすることを特徴とするものである。 In addition, the profilagrin and / or filaggrin production promoter of the present invention has the following general formula (1),

(Wherein R ¹ and R ² each independently represent a hydrogen atom, an acyl group having 3 to 20 carbon atoms which may have a substituent or may have a branch, and R ¹ and it is characterized in that the Keburanin acids or a salt thereof as an active ingredient having a skeleton R ² is represented by and may form a cyclic group) linking.

  Furthermore, it is preferable that the quebrains are one or more selected from the group consisting of quebragic acid, ketulinic acid and quebrinine.

  Furthermore, the profilagrin and / or filaggrin production promoter of the present invention can be suitably used as a skin external preparation.

  Production of profilagrin and / or filaggrin can be effectively promoted by the profilagrin and / or filaggrin production promoter of the present invention. In addition, profilagrin and / or filaggrin production promoter having a high skin conditioning effect could be provided. Further, the profilagrin and / or filaggrin production promoter of the present invention can improve symptoms associated with ichthyosis vulgaris such as reduction of keratohyaline granules, reduction of amino acids in the stratum corneum and scaling.

Hereinafter, a preferred embodiment of the present invention will be specifically described.
The profilagrin and / or filaggrin production promoter of the present invention contains a milobalan fruit extract as an active ingredient, but the milobalan fruit extract can be obtained by a conventional method, for example, the fruit of milobalan together with an extraction solvent. After soaking or heating under reflux, the mixture 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 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.

（式中、Ｒ^１及びＲ^２は、各々独立して、水素原子又は置換基を有してもよく分岐を有していてもよい炭素原子数３〜２０、好ましくは７〜１５のアシル基を表し、Ｒ^１とＲ^２が連結して環状基を形成してもよい）で表される骨格を有するケブラニン類またはその塩を有効成分とするものである。ケブラニン類またはその塩としては、上記一般式（１）の骨格を有するものであれば、特に限定されないが、Ｒ^１及びＲ^２は、好ましくは、水素原子、３つの水酸基を有するベンゾイル基、または３つの水酸基を有するベンゾイル基同士が結合して、環状基を形成しているもの等を挙げることができる。 Another profilagrin and / or filaggrin production promoter of the present invention is represented by the following general formula (1),

(In the formula, R ¹ and R ² are each independently an acyl group having 3 to 20 carbon atoms, preferably 7 to 15 carbon atoms which may have a hydrogen atom or a substituent and may have a branch. And R ¹ and R ² may be linked to form a cyclic group), and a kebranine having a skeleton represented by the following formula or a salt thereof is used as an active ingredient. Kebulin or a salt thereof is not particularly limited as long as it has a skeleton of the above general formula (1), but R ¹ and R ² are preferably a hydrogen atom, a benzoyl group having three hydroxyl groups, or A benzoyl group having three hydroxyl groups may be bonded to form a cyclic group.

  Such ketranins or salts thereof can be obtained by extraction from plants, isolation, or synthesis by known methods. In particular, it can be suitably obtained by obtaining a milobaran fruit extract from the milobaran fruit by the above method and then isolating it. The isolation method is not particularly limited, but it can be suitably isolated by techniques such as liquid-liquid distribution, various chromatographies, and recrystallization. The melovaran fruit extract thus obtained and the quebranins having a skeleton of the above general formula (1) or a salt thereof in the myrobalan fruit extract have an excellent profilaggrin and / or filaggrin production promoting action. The profilagrin and / or filaggrin production promoter of the present invention can be used in various fields such as pharmaceuticals, quasi drugs, foods and cosmetics.

  In addition, the profilagrin and / or filaggrin production promoter of the present invention is preferably one type in which the ketranins are selected from the group consisting of chebulagic acid, chebulinic acid and chebulanin. Or they are 2 or more types, More preferably, they are the high profilagrin and / or a filaggrin production promotion effect | action, and are the kebulinic acid and kebulin with much content. Each component can be obtained by the above method. Each of the components contained in the thus-obtained milobaran fruit extract and milobaran fruit extract has an excellent profilagrin and / or filaggrin production promoting action.

  When the profilagrin and / or filaggrin production promoter of the present invention is used as an external preparation for skin, the extract of milobaran fruit, the kebranin having a skeleton represented by the above general formula (1) or a salt thereof, and the extract of milobaran fruit The amount of kebrugic acid, kebulinic acid and kebulin (hereinafter referred to as “mylobalan fruit extract etc.”), which is a component of the product, varies depending on the type of active ingredient, dosage form, etc. In the total amount of the external preparation, the dry weight is 0.0001 to 5%, more preferably 0.001 to 0.1%. Below this range, profilaggrin and / or filaggrin production-promoting effect is difficult to be exerted sufficiently, and if it exceeds this range, the increase in effect cannot be expected, and it is not economical, stickiness, smell unique to crude drugs, use This is not preferable because the feeling of sensation and the problem of dyeing with crude drugs occur.

  In the present invention, in addition to the above-mentioned myrobalan fruit extract and the like, in addition to the above-mentioned myrobalan fruit extract, within the range that does not impair the effects of the present invention, other components usually used in skin external preparations such as cosmetics and pharmaceuticals, Moisturizer, oil component, surfactant, vitamins, proteolytic enzyme, thickener, preservative, powder, antioxidant, UV absorber, emulsifier, alcohol, color material, aqueous component, water, various skin A nutrient etc. can be suitably mix | blended as needed.

  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 and other waxes, 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 alkyl phenyl 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, carboxymethylcellulose, 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, etc. Can be mentioned. Examples of other components include fragrances, pigments, and bactericides.

  Further, the external preparation for skin of the present invention can be used in cosmetics, bathing agents, cleaning agents, facial cleansers, etc., and the dosage form is arbitrary, for example, lotion, emulsion, cream, ointment, dispersion, gel Shapes, powders, aerosols, packs and the like.

  Moreover, it is preferable to use the profilagrin and / or filaggrin production promoter of the present invention as an agent for improving ichthyosis vulgaris. In this case, the decrease in keratohyalin granules, the decrease in amino acids in the stratum corneum, and scaling can be suppressed, and the ichthyosis vulgaris, which is an inherited abnormal keratosis disease, can be improved.

Hereinafter, the present invention will be described in detail according to examples.
Experimental example 1
Example of preparation of myrobalan fruit extract To 20 g of myrobalan fruit (dried product), 200 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 powder could be obtained. Separately, after insoluble matter was filtered out from 50.28 g of myrobalan fruit extract obtained by room temperature extraction with 60% acetone, Sephadex LH-20 (Pharmacia), MCI gelCHP20P (Mitsubishi Chemical Co., Ltd.) As a result of separation and purification by subjecting to various column chromatography using cellulose and ODS gel, the yields shown in Table 1 below were obtained as shown in Table 1. (Corilagin) was obtained.

Experimental example 2
Profilaggrin / filaggrin production promoting action confirmation test Normal human newborn skin epidermal keratinocytes (NHEK) were cultured in a normal human epidermal keratinocyte medium (KGM) at 37 ° C. under 5% CO ₂ in an 80 cm ² flask. Cells were collected by conventional methods. The obtained cells were adjusted to 1.5 × 10 ⁵ cells / mL in the same medium, seeded on a 6-well collagen-coated plate by 2 mL and cultured at 37 ° C. for 4 days under 5% CO ₂ . After culturing, the sample was replaced with ₂ mL of KGM containing or not containing the test sample dissolved in 0.25% DMSO (control) and cultured at 37 ° C. under 5% CO ₂ for 5 days. After completion of the culture, total protein was prepared by a conventional method.

(Western blotting)
The sample adjusted to 10 μg / lane was developed by SDS-PAGE and transferred to a PVDF membrane. After blocking with PBS (-) containing 5% skim milk, anti-human filaggrin monoclonal antibody (manufactured by Harbor BioProducts), biotin-labeled anti-mouse Ig (Whole Ab) (manufactured by Amersham Biosciences), streptavidin-peroxidase complex (CALBIOCHEM Made by PBS (-) containing 0.1% Tween20 and 0.3% skim milk, and then sequentially reacted, and profilagline was obtained by luminescence of ECL Westernblotting detection reagents and analysis system (Amersham Biosciences). And filaggrin was detected. The detected band was quantitatively measured with KODAK 1D Image Analysis Software EDAS290 Version3.5.

Examples 1-3 and Comparative Examples 1-3
As test samples, as examples, myrobalan fruit extract powder (Example 1), keblagic acid (Example 2) and kebranin (Example 3), which are the main components of myrobalan fruit extract, and punicalagin as a comparative example. (Comparative Example 1), gallic acid (Comparative Example 2) and corilagin (Comparative Example 3) were used to adjust each sample to a concentration of 25 μg / mL.

Examples 4 and 5 and Comparative Examples 4 to 6
As test samples, as examples, myrobalan fruit extract powder (Example 4) and kevulinic acid (Example 5), as comparative examples, punicalagin (Comparative Example 4), gallic acid (Comparative Example 5) and corilagin (Comparative Example) Each sample was adjusted to a concentration of 6.25 μg / mL and used.

  As a result, the profilaggrin / filaggrin production promoting action of the test sample was evaluated using the profilagrin and filaggrin band strength (Netintensity) in 10 μg of the protein prepared from each of the cells cultured with and without the test sample added.

The calculation method of the profilaggrin / filaggrin production promoting action is shown in Table 2, and the results at a concentration of 25 μg / mL are shown in Table 2, and the results at a concentration of 6.25 μg / mL are shown in Table 3.
Calculation formula Profilagrin / Filagulin production promotion rate (%) = A / B × 100
(In the formula, A is the band intensity when the test sample is added, and B is the band intensity when the test sample is not added (control)).

  From Table 2 and Table 3 above, all of the examples showed significantly profilaggrin / filaggrin production promoting action, in particular, the extract of fruit extract of milobalan (Examples 1 and 4), kebulin (Example 3) and kebulinic acid (implemented) In Example 5), the effect was remarkable.

Experimental example 3
Preparation Example of External Preparation for Skin (Cream Formulation) The milobaran fruit extract powder obtained in Experimental Example 1 was dissolved in a 50% butanol aqueous solution to obtain a 2% milobaran extract. Using this, according to the prescription (% by weight) shown in Table 4 below, a hand cream preparation containing 0.5% mylobaran fruit extract (hereinafter referred to as “mylobalan-containing cream”) was prepared according to the following production example.

  First, liquid paraffin, isopropyl palmitate, stearic acid, cetanol, glyceryl monostearate, dimethylpolysiloxane, decamethyltetrasiloxane, butylparaben, decaglyceryl monostearate, and tocopherol acetate were mixed and heated. Next, methyl paraben, 1,3-butylene glycol, 1,2-pentanediol, concentrated glycerin, disodium edetate, triethanolamine, and purified water were mixed and heated, and added to the previous mixture for emulsification. After cooling, a hand cream was prepared by adding phenoxyethanol, dipotassium glycyrrhizinate, flavor, and 2% myrobalan fruit extract.

  According to the formulation (% by weight) shown in Table 5 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 (1) containing a milobaran fruit extract having a pH of 6.1.

  According to the formulation (% by weight) shown in Table 6 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 (2) containing a myobalan fruit extract having a pH of 7.5.

  According to the formulation (% by weight) shown in Table 7 below, the oil phase and the aqueous phase were each heated to 70 ° C. and completely dissolved. An oil phase was added to the water 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 4
Example of preparation of bathing agent According to the formulation (% by weight) shown in Table 8 below, a powder bathing agent containing a milobaran fruit extract was prepared by uniformly mixing all raw materials.

  In accordance with the formulation (% by weight) shown in Table 9 below, the A phase and the B phase are heated to 70 ° C. to completely dissolve them, and after adding the A phase to the B phase, the mixture is cooled to 30 ° C. Was prepared.

Experimental Example 5
Example of preparation of skin lotion According to the formulation (% by weight) shown in Table 10 below, an alcoholic phase is added to the aqueous phase to prepare a stock solution, and the stock solution is placed in a can and filled with a gas such as LPG or butane to extract a milobaran fruit. A product-containing lotion (aerosol product) was prepared.

  In accordance with the formulation (% by weight) shown in Table 11 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 at pH 5.5.

  According to the formulation (% by weight) shown in Table 12 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 13 below, the aqueous phase was solubilized by adding an alcohol phase, and then the powder phase was added to make a three-layered type milobaran fruit extract-containing lotion ( Separate type) was prepared.

Experimental Example 6
Preparation example of tonic According to the formulation (% by weight) shown in Table 14 below, first, dl-α-tocopherol acetate, isopropylmethylphenol, pantothenyl alcohol, glycyrrhetinic acid, ethanol (99.5%), octyldodecyl myristate, 2- Octyl ethyl henxanthate, flavor, and menthol were mixed uniformly. Next, assembly extract, carrot extract, 1,3-butylene glycol, dipropylene glycol, sodium ascorbate phosphate, tetrasodium edetate, polyoxyethylene hydrogenated castor oil (50E.O), polyoxyethylene hardened Castor oil (20E.O), 2% myrobalan fruit extract, and purified water were mixed uniformly. Finally, both were mixed, filtered and filled to prepare a liquid type tonic containing a milobaran fruit extract.

  According to the formulation (% by weight) shown in Table 15 below, first, dl-α-tocopherol acetate, isopropylmethylphenol, pantothenyl alcohol, ethanol (99.5%), flavor, and menthol were uniformly mixed. Next, assembly extract, carrot extract, dipropylene glycol, 3-methyl-1,3-butanediol, sodium ascorbate phosphate, tetrasodium edetate, polyoxyethylene polyoxypropylene glycol, decaglyceryl monolaurate 2% 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-type tonic containing milobaran fruit extract.

Experimental Example 7
Example of application as an external skin preparation A cream formulation containing 0.5% of milobaran fruit extract obtained in Experimental Example 3 and only a base as a comparative example were applied to the left and right dorsum (back of hand) of a 30-year-old woman 3 times a day. A large amount of soybean was applied, and the skin gloss, firmness, softness, rustle, dullness, texture and wrinkle before and after application for 1 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), somewhat arrogant (2), neither can be said (3), slightly fine (4), fine (5)”
Wrinkle: “I stand out (1), I stand out slightly (2), I can't say either (3), I don't stand out very much (4), I don't stand out (5)”

  From the evaluation results, it is clear that the Milobaran fruit extract is effective in any of the items of gloss, firmness, softness, crispness, dullness, texture and wrinkle before application and in comparison with the base alone Compared with the base alone, when the external preparation for skin containing the milobaran fruit extract was used, it had a skin conditioning effect that finely adjusted the texture. In addition, moisturizing power and elasticity improved, and dullness disappeared. Furthermore, it showed the possibility of improvement of symptoms associated with ichthyosis vulgaris such as reduction of keratohyalin granules, reduction of amino acids in the stratum corneum and scaling.

Claims (4)

  A profilagrin and / or a filaggrin production promoter characterized by comprising an extract of myrobalan fruit as an active ingredient. The following general formula (1),

(Wherein R ¹ and R ² each independently represent a hydrogen atom, an acyl group having 3 to 20 carbon atoms which may have a substituent or may have a branch, and R ¹ and A profilagrin and / or filaggrin production promoter characterized by containing as an active ingredient a kebranin having a skeleton represented by the following formula: R ² may be linked to form a cyclic group.   The profilaggrin and / or filaggrin production promoter according to claim 2, wherein the quebranins are one or more selected from the group consisting of quebragic acid, ketulinic acid and quebrinine.   It is a skin external preparation, The profilagrin and / or a filaggrin production promoter as described in any one of Claims 1-3.