JP6646528B2 - Keratin plug decomposition accelerator - Google Patents

Description

  TECHNICAL FIELD The present invention relates to a keratotic plug degradation accelerator characterized by containing a yugao extract.

  The keratin plug is considered to be sebum secreted from the surrounding keratin and sebaceous glands coagulated and developed in the pores, and is considered to be one of the causes of conspicuous pores. For this reason, treatments such as physically removing the horn plug have been proposed, such as a method of removing the horn plug by washing the face (Patent Literature 1), a method of attaching the lip plug to an adhesive sheet or the like (Patent Document 2), A removal instrument (Patent Document 3) and the like have been devised. Further, as an alternative method, a method and a preparation (Patent Document 4) for suppressing corneal plug regeneration in which a surfactant is added to a high-concentration organic acid have been proposed.

  Yugao is used for food as a camphor but also as a raw material for cosmetics. Its main patent documents are cosmetics having an antioxidant effect (Patent Document 5) and cosmetics having a whitening effect (Patent Documents). 6, 7), cosmetics having a collagen production promoting action (Patent Document 8), hair restorer (Patent Document 9), and cosmetics having an effect of improving dry skin and giving the skin a glossiness (Patent Document 10). Can be

  Pomegranate contains antioxidant components such as ellagic acid and can be expected to have an anti-aging effect.In addition, since it contains a female hormone-like component and can be expected to have an effect on beauty and health, its flowers, fruits, seeds, etc. It is used as a raw material for health foods and cosmetics. In addition, it was reported that lactic acid fermentation liquid of pomegranate showed the action of suppressing the formation of inner root sheath and the activation of androgen involved in the formation of keratotic plugs, and the effect of preventing the prominence of keratotic plugs and pores. (Patent Document 11).

JP 2007-119394 A JP 2007-55933 JP 2009-82376A JP 2013-49667 JP-A-2002-138028 JP 2014-55121A JP 2014-224081A JP 2005-255527 JP-A-6-247832 JP-A-2001-226249 JP-A-2015-168628

  In the method of removing keratotic plugs using a pressure-sensitive adhesive sheet or device developed so far, the keratin of the epidermis is also lost, and there is a concern that the skin may become rough. In addition, the method of suppressing the regeneration of keratotic plugs by adding a surfactant to a high concentration of organic acid is also based on the chemical dissolution of keratotic plugs. Absent. This is due to the fact that the details of the mechanism involved in the formation and degradation of keratotic plugs are unknown, and there are few studies on keratotic plug components. Recently, it has been revealed that about 70% of keratotic plugs are composed of proteins (Mizukoshi Koji et al., J. Soc. Cosmet. Chem. Jpn. 41, 262-268 (2007)), and that keratin plugs are formed. Was considered an important factor. Furthermore, protein analysis of keratin plugs reported that keratin 17 was present in keratin plugs (Hiroko Yamazaki et al., The 73rd SCCJ Meeting, Abstracts, p14-15, Held November 29, 2013) Not all of the proteins that make up the horn plug have been elucidated, and there are still many unclear points about the horn plug formation mechanism, the horn plug degradation mechanism, and the constituent proteins. In view of the above background, in order to remove keratotic plugs without causing rough skin, it has been desired to develop a new keratotic plug degradation promoter based on constituent proteins in the keratotic plugs.

  In view of such a situation, an object of the present invention is to provide a cathepsin V activity promoting agent containing a crude drug component based on a keratotic decomposition mechanism.

  The present inventors have revealed from protein analysis of hair follicles that cathepsin V, which is a proteolytic enzyme, is localized inside the keratin plug. Cathepsin V enzyme activity in the horn plug was higher for the smaller horn plug. Furthermore, the amount of corneodesmosin, which is a cell adhesion factor in the keratin plug, and the amount of cathepsin V are in an inverse relationship, and the amount of corneodesmosin is large while the amount of cathepsin V is small, but the amount of cathepsin V is small, but the pores and corn plug are conspicuous. If not, the relationship was reversed. Under these circumstances, cathepsin V is a keratolytic enzyme, and as a result of intensive studies that cathepsin V activity could be a means of promoting keratotic degradation, as a result of the research, it was found that catharsin extract showed cathepsin V activity. It has been found that it has a promoting action and an action of promoting the decomposition of keratotic plugs. Furthermore, they have found that the combined use of the yugao extract and the pomegranate extract exerts a synergistic effect on the improvement of conspicuous pores, and completed the present invention.

  That is, the present invention is as follows.

  A cathepsin V activity promoter comprising a yugao extract.

  A keratotic plug degradation accelerator comprising a yugao extract.

  An agent for improving the conspicuousness of pores, comprising a yugao extract.

  An agent for improving the conspicuousness of pores, comprising a yugao extract and a pomegranate extract.

  The yugao extract of the present invention is a natural and highly safe material, and since an excellent cathepsin V activity promoting effect was recognized, an effect of improving the conspicuousness of pores by decomposing proteins in the corneal plug can be expected, It can be applied to pharmaceuticals, quasi-drugs, cosmetics, foods, etc. The yugao extract of the present invention has a keratotic plug degradation promoting action and can be used in the fields of pharmaceuticals, quasi-drugs, cosmetics, and foods.

  Hereinafter, the present invention will be described in more detail.

  The yugao extract used in the present invention is an extract of yugao fruit. Yugao is a family of Cucurbitaceae, the genus Hypogalus, and Yugao, whose scientific name is Lagenaria sicaria (L. siceria var. Hispida, L. genus var. Var. A. The fruit may include flesh, pericarp, seeds, and may include marc. In the extract of the fruit of Gypsophila which can be used in the present invention, the solvent to be extracted includes, for example, water, alcohols and acetone. It may be extracted using one or more of these water-soluble solvents. Further, it may be one extracted by heating or one extracted at normal temperature.

  The yugao extract may be used as it is, or may be used as a cosmetic raw material after being subjected to extraction, concentration, dilution, filtration and the like, and decolorization and deodorization treatment with activated carbon or the like, if necessary.

  The pomegranate extract used in the present invention is an extract, fruit juice, or fermentation of extract or juice from a part or whole plant of a plant such as a flower, fruit, seed, stem, leaf, root, etc. of pomegranate (Punica granatum) Liquid. The extraction method is not particularly limited, and may be, for example, the one extracted by heating or the one extracted at room temperature. It is preferably a fruit juice, which may include pulp, pericarp, seeds and may include marc. The fruit juice may be used as it is, unadjusted or concentrated juice, or may be used after dilution. The pH may be adjusted to 3 to 8 with an alkali such as sodium hydroxide. More preferably, organic substances such as yeast extract and soybean peptide, and minerals such as magnesium sulfate may be added for the purpose of promoting the growth of lactobacilli. The juice of the present invention also includes a pomegranate solvent extract extracted with a solvent such as water or ethanol.

  In the fermentation liquid, for example, lactic acid bacteria can be used, and the lactic acid bacteria to be used belong to the genus Lactobacillus, Lactococcus, Lactococcus, Leuconostoc, or Pediococcus. Lactic acid bacteria. Particularly preferred is a lactic acid bacterium belonging to Lactobacillus plantarum from the viewpoint of improving the effectiveness by fermentation, and particularly a strain isolated from a plant or pickled food that is a fermented food thereof, even if it is a strain preservation institution. May be registered. Further, it is particularly preferable that the pomegranate juice can be efficiently fermented in the pH range of 3 to 5. Culture conditions can be set as appropriate, and it is desirable to carry out at 25 to 40 ° C. as a guide.

  The application of the present invention to an external preparation or an internal preparation may be carried out by using the above extract as it is, or used in cosmetics, quasi-drugs, medicines, foods, etc. as long as the effect of the extract is not impaired. Ingredients fats and oils, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, ultraviolet absorbers, thickeners Ingredients such as agents, pigments, antioxidants, whitening agents, chelating agents, excipients, film agents, sweeteners, and sour agents can also be appropriately contained.

  Examples of the dosage form of the present invention include lotions, creams, massage creams, emulsions, gels, aerosols, packs, detergents, baths, foundations, powders, lipsticks, ointments, cataplasms, pastes, and plasters , Essences, powders, pills, tablets, injections, suppositories, emulsions, capsules, granules, liquids (including tinctures, fluid extracts, alcoholic beverages, suspensions, limonades, etc.), tablets, Drinks and the like are included.

  The content of the citrus extract used in the present invention when used in the form of a solution is not particularly limited, but is preferably 0.00001% by weight or more, preferably 0.001 to 5.0% by weight in terms of solids. . If the amount is less than 0.00001% by weight, the effects of the present invention may not be sufficiently exhibited. The method of addition may be added in advance or may be added during the production, and may be appropriately selected in consideration of workability.

  The content of the pomegranate extract used in the present invention in the form of a solution is not particularly limited, but is preferably 0.001% by weight or more, preferably 0.001 to 5.0% by weight in terms of solids. . If the amount is less than 0.001% by weight, the effects of the present invention may not be sufficiently exhibited. The method of addition may be added in advance or may be added during the production, and may be appropriately selected in consideration of workability.

  Cathepsin V in the present invention is a proteolytic enzyme belonging to cysteine protease, and is sometimes referred to as cathepsin L2 as another name. It is expressed in skin epidermal cells, the inner root sheath in hair follicles, etc., and has been identified as an enzyme involved in keratin desquamation. D. Bernard, et al. J. Invest. Dermatol. 120, 592-600 (2003) and Patrick LJM Zeewen, et al. J. Invest. Dermatol. 127, 592-600 (2007)). . It has also been shown to be localized in lysosomes in cells and involved in proteolysis (Y. Miwa, et al. FEBS Lett. 586, 3601-3607 (2012)). It has been pointed out that there is a relationship between skin color and cathepsin V, and application to whitening cosmetics and the like is expected (N. Chen, et al. J. Invest. Dermatol. 126, 2345-2347 (2006)). ). Furthermore, cathepsin V is expressed in cancer cells (I. Santamaria, et al. Cancer Res. 58, 1624-1630 (1998)) and is considered to be involved in the progression of cancer such as metastasis of cancer. Therefore, application to medical treatment such as cancer diagnosis and treatment is expected.

Next, in order to explain the present invention in detail, Production Examples, Formulation Examples and Experimental Examples of Yugao extract used in the present invention will be given as Examples, but the present invention is not limited thereto. The contents in the examples are all by weight.
Hereinafter, production examples of the yugao extract and the pomegranate extract will be described.

Production Example 1
500 g of the fruit of Yugao was shredded, heat-extracted twice with 500 ml of water for 2 hours each, and concentrated by vacuum freeze-drying to obtain 1 g of the extract (containing 99% or more solids).

Production Example 2
After 100 g of camphor (commercially available) was sufficiently washed with water, it was heated and extracted twice with 1000 ml of water for 2 hours each. After filtering the residue, the filtrate was concentrated under reduced pressure, and further freeze-dried in vacuo to obtain 6 g of an extract (containing 99% or more solids).

Production Example 3
60 g of dried yugao fruit was ground, extracted with 600 ml of a water-ethanol mixture (1: 1) under heating for 5 hours, and further concentrated to obtain 2 g of the extract (containing 50% solids).

Production Example 4
60 g of dried yugao fruit was pulverized, 300 ml of ethanol was added, and the mixture was allowed to stand at room temperature for one month. By further concentrating, 1 g (including 99% or more solids) was obtained.

Production Example 5
60 g of dried yugao fruit was pulverized, extracted twice with 600 ml of propanol at room temperature twice for 2 hours, and further concentrated to obtain 1 g of the extract (containing 70% solids).

Production Example 6 Pomegranate Juice A commercially available concentrated pomegranate juice (Brix65) prepared by a squeezing method was used.

Production Example 7 Fermented Liquid of Pomegranate Juice A commercially available concentrated pomegranate juice (Brix65) was diluted with water to adjust the concentration to Brix15, and adjusted to pH5 using an aqueous sodium hydroxide solution. To 500 g of the prepared solution, a seed strain of lactic acid bacteria (derived from pickles) belonging to Lactobacillus plantarum was added. The mixture was fermented at 30 ° C. for 2 days and filtered to obtain 450 g of fermented pomegranate juice.

Production Example 8 Fermented Liquid of Pomegranate Juice A commercially available concentrated pomegranate juice (Bix65) was diluted with water to adjust the concentration to Brix11, and the pH was adjusted to 4.5 using an aqueous sodium hydroxide solution. To 500 g of the prepared solution, a seed strain of lactic acid bacteria (derived from pickles) belonging to Lactobacillus plantarum was added. The mixture was fermented at 30 ° C. for 2 days and filtered to obtain 450 g of fermented pomegranate juice.

Production Example 9 Fermented Liquid of Pomegranate Juice A commercially available concentrated pomegranate juice (Brix65) was diluted with water to adjust the concentration to Brix8, and the pH was adjusted to 4.5 using an aqueous sodium hydroxide solution. To 500 g of the prepared solution, a seed strain of lactic acid bacteria (derived from pickles) belonging to Lactobacillus plantarum was added. The mixture was fermented at 30 ° C. for 2 days and filtered to obtain 450 g of fermented pomegranate juice.

Production Example 10 Fermented Liquid of Pomegranate Juice A commercially available concentrated pomegranate juice (Bix65) was diluted with water to adjust the concentration to Brix5, and the pH was adjusted to 4.5 using an aqueous sodium hydroxide solution. To 500 g of the prepared solution, a seed strain of lactic acid bacteria (derived from pickles) belonging to Lactobacillus plantarum was added. The mixture was fermented at 30 ° C. for 2 days and filtered to obtain 450 g of fermented pomegranate juice.

Production Example 11 Fermented Liquid of Pomegranate Juice To 210 g of the fermented product of pomegranate juice of Example 8, 90 g of 1,3-butylene glycol was added and filtered to obtain 280 g of a fermented product of pomegranate juice.

  In the following, examples of prescription using the yugao extract and the pomegranate extract are shown.

Formulation Example 1 Lotion (ingredient) (% by weight)
1. Yugao extract (Production Example 2) 0.5
2.1,3-butylene glycol 8.0
3. Glycerin 2.0
4. Xanthan gum 0.02
5. Citric acid 0.01
6. Sodium citrate 0.1
7. Ethanol 5.0
8. Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40EO) 0.1
10. Perfume appropriate amount 11. [Production method] Components 1 to 6 and 11 and components 7 to 10 each having a total amount of 100 with purified water are uniformly dissolved, and both are mixed and filtered to obtain a product.

Comparative Example 1 Conventional lotion A conventional lotion was prepared by replacing the yugao extract (Preparation Example 2) in Formulation Example 1 with purified water.

Formulation Example 2 Emulsion A
(Ingredient) (% by weight)
1. Yugao extract (Production Example 4) 0.5
2. Squalane 5.0
3. Olive oil 5.0
4. Jojoba oil 5.0
5. Cetanol 1.5
6. Glycerin monostearate 2.0
7. Polyoxyethylene cetyl ether (20EO) 3.0
8. Polyoxyethylene sorbitan monooleate (20EO) 2.0
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12. Methyl paraoxybenzoate 0.2
13. [Production method] Components 2 to 8 are heated and dissolved in purified water to make the total amount 100, and the mixture is mixed and kept at 70 ° C to obtain an oil phase. The components 1 and 10 to 13 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The oil phase is added to the water phase, emulsified, cooled while stirring, and the component 9 is added at 45 ° C, and further cooled to 30 ° C to obtain a product.

Comparative Example 2 Conventional Emulsion A conventional emulsion was prepared by replacing Yugao extract (Preparation Example 4) with purified water in Formulation Example 2.

Formulation Example 3 Cream (ingredient) (% by weight)
1. Yugao extract (Production Example 1) 0.5
2. Squalane 5.5
3. Olive oil 3.0
4. Stearic acid 2.0
5. Beeswax 2.0
6. Octyldodecyl myristate 3.5
7. Polyoxyethylene cetyl ether (20EO) 3.0
8. Behenyl alcohol 1.5
9. Glycerin monostearate 2.5
10. Fragrance 0.1
11. Methyl paraoxybenzoate 0.2
12. Ethyl paraoxybenzoate 0.05
13.1,3-butylene glycol 8.5
14． [Production method] Components 2 to 9 are heated and dissolved in purified water to make the total amount 100, and the mixture is kept at 70 ° C to obtain an oil phase. The components 1 and 11 to 14 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase, emulsified, cooled while stirring, and the component 10 is added at 45 ° C, and further cooled to 30 ° C to obtain a product.

Comparative Example 3 Conventional Cream A conventional cream was prepared by substituting the watermelon extract (Preparation Example 1) in Formulation Example 3 with purified water.

Formulation Example 4 Gel (component) (% by weight)
1. Yugao extract (Production Example 5) 0.5
2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4. Polyoxyethylene hydrogenated castor oil (60EO) 0.1
5. Fragrance appropriate amount 6.1,3-butylene glycol 5.0
7. Glycerin 5.0
8. Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. [Production method] Components 2 to 5 and components 1 and 6 to 11 each having a total amount of 100 in purified water are uniformly dissolved, and both are mixed to obtain a product.

Formulation Example 5 Bath agent (component) (% by weight)
1. Yugao extract (Production Example 2) 1.0
2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Suitable amount 4. Appropriate amount of fragrance 5. [Production method] Components 1 to 5 are adjusted to a total amount of 100 with sodium sulfate to obtain a product.

Formulation Example 6 Tablet (ingredient) (% by weight)
1. Yugao extract (Production Example 1) 5.0
2. Dried corn starch 25.0
3. Carboxymethylcellulose calcium 20.0
4. Microcrystalline cellulose 40.0
5. Polyvinylpyrrolidone 7.0
6. Talc 3.0
[Production method] Components 1 to 4 are mixed, and then an aqueous solution of component 5 is added as a binder and granulated. Ingredient 6 is added to the formed granules and tableted. One tablet is 0.52 g.

Formulation Example 7 Tablets (Ingredients) (% by weight)
1. Yugao extract (Production Example 2) 2.0
2. Dried corn starch 49.8
3. Erythritol 40.0
4. Citric acid 5.0
5. Sucrose fatty acid ester 3.0
6. Fragrance 0.1
7. Purified water 0.1
[Production method] Components 1 to 4 and 7 are mixed and granulated. Ingredients 5 and 6 are added to the molded granules and tableted. One grain is 1.0 g.

Formulation Example 8 Emulsion B
(Ingredient) (% by weight)
1. Yugao extract (Production Example 4) 0.5
2. Pomegranate fermented liquid (Production Example 11) 0.5
3. Squalane 5.0
4. Olive oil 5.0
5. Jojoba oil 5.0
6. Cetanol 1.5
7. Glycerin monostearate 2.0
8. Polyoxyethylene cetyl ether (20EO) 3.0
9. Polyoxyethylene sorbitan monooleate (20EO) 2.0
10. Fragrance 0.1
11. Propylene glycol 1.0
12. Glycerin 2.0
13. Methyl paraoxybenzoate 0.2
14． [Production method] Components 3 to 9 are heated and dissolved in purified water to make the total amount 100, and the mixture is mixed and kept at 70 ° C to obtain an oil phase. Components 1-2 and 11-14 are dissolved by heating and mixed, and the mixture is kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase, emulsified, cooled while stirring, and the component 10 is added at 45 ° C, and further cooled to 30 ° C to obtain a product.

Formulation Example 9 Emulsion C
(Ingredient) (% by weight)
1. Fermented liquid of pomegranate juice (Production Example 11) 0.5
2. Squalane 5.0
3. Olive oil 5.0
4. Jojoba oil 5.0
5. Cetanol 1.5
6. Glycerin monostearate 2.0
7. Polyoxyethylene cetyl ether (20EO) 3.0
8. Polyoxyethylene sorbitan monooleate (20EO) 2.0
9. Fragrance 0.1
10. Propylene glycol 1.0
11. Glycerin 2.0
12. Methyl paraoxybenzoate 0.2
13. [Production method] Components 2 to 8 are heated and dissolved in purified water to make the total amount 100, and the mixture is mixed and kept at 70 ° C to obtain an oil phase. The components 1 and 10 to 13 are dissolved by heating and mixed, and kept at 75 ° C. to obtain an aqueous phase. The oil phase is added to the water phase, emulsified, cooled while stirring, and the component 9 is added at 45 ° C, and further cooled to 30 ° C to obtain a product.

  Hereinafter, experimental examples will be described to effectively explain the present invention. Note that the present invention is not limited to this.

Experimental Example 1 Cathepsin V activity measurement 1
The enzymatic activity promoting effect of cathepsin V was measured under the following conditions.

  The enzymatic reaction of cathepsin V was performed using 50 ng human recombinant cathepsin V protein (R & D), 9 μM (final concentration) as a substrate, Z-Leu-Arg-7-Amino, 4-Methyl Coumarin (R & D), and 10 μg / ml (final). (Concentration) in a reaction buffer solution (25 mM Sodium Acetate, 0.1 M NaCl, 5 mM dithiothreitol, pH 5.5) containing a sample of the extract of Yugao extract at 37 ° C. The amount of the reaction product (7-Amino, 4-Methyl Coumarin) during the enzymatic reaction was measured by a fluorescent plate reader SpectraMax Gemini EM (Molecular Device).

  The test results are shown in Table 1. The cathepsin V enzyme activity under the non-addition condition was 57.6 pmol / min · μg enzyme. On the other hand, the cathepsin V enzyme activity under the conditions where the yugao extract was added was 80.6 pmol / min · μg enzyme, which was 140% as compared with the condition where no yugao extract was added, indicating that the yugao extract has an effect of promoting the enzyme activity of the cathepsin V. Was.

Catharsin V activity promoting effect of yugao extract

Experimental Example 2 Cathepsin V activity measurement 2
The enzymatic activity promoting effect of cathepsin V was measured under the following conditions.

  The enzymatic reaction of cathepsin V was performed using an ultrasonically crushed horn plug collected from a cheek of a subject with a pore removing sheet as an enzyme source. 110 μl of a reaction buffer solution containing 140 μg of a crushed sonicated plug, 9 μM (final concentration) Z-Leu-Arg-7-Amino, 4-Methyl Coumarin (R & D) as a substrate, and yugao extract or cucumber extract ( In 25 mM Sodium Acetate, 0.1 M NaCl, 5 mM dithiothreitol, pH 5.5) at 37 ° C. The amount of the reaction product (7-Amino, 4-Methyl Coumarin) during the enzymatic reaction was measured by a fluorescent plate reader SpectraMax Gemini EM (Molecular Device). As the cucumber extract, Cucumber Organic manufactured by Ichimaru Falcos and containing 0.2% of the cucumber extract was diluted to a desired concentration.

  The test results are shown in Table 2. Cathepsin V enzyme activity under no addition conditions was 0.105 pmol / min · μg protein. On the other hand, the cathepsin V enzyme activity under the conditions of addition of yugao extract was 0.117 pmol / min · μg protein when adding 1.0 μg / ml of yugao extract, 0.138 pmol / min · μg protein when adding 10.0 μg / ml, 100 When 0.1 μg / ml was added, the protein was 0.142 pmol / min · μg protein, which was 112%, 132%, and 135%, respectively, compared to the condition where no protein was added. Yugao extract promoted the enzymatic activity of cathepsin V contained in the horn plug. Has the effect of causing The cathepsin V enzyme activity under the cucumber extract addition condition was 0.096 pmol / min · μg protein, which was 91% as compared with the non-added condition, and 68% as compared with the same concentration as the addition of yugao extract. The specificity of the activity promoting action was confirmed.

Influence of yugao extract and cucumber extract on cathepsin V activity in keratin plugs

Experimental example 3 Continuous use test 1
Using Formulation Example 2 and Comparative Example 2 of Emulsion A containing Yugao extract, a one-month continuous test was performed on eight male and female subjects in their 20s to 50s. A blind test in which the test subject is not notified of the presence or absence of the active ingredient, and a half-side test in which the prescription example 2 containing the active ingredient on one cheek of the subject and the comparative example 2 are continuously used on the other cheek They were used twice a day in the morning and evening for one month. Porphyrin fluorescence, which is an indicator of keratosis formation, was measured on the cheeks before and after one month of continuous application. At the same time, a replica of the cheek was collected with a replica agent SILFLO (FLEXICO), and the pore area ratio was calculated using the replica.

  The amount of porphyrin, which is an index of a keratotic plug, is obtained by obtaining an ultraviolet image of the cheek using a keratoscope scope, “Charm View” (Moritex Corporation), smoothing the image with a Gaussian filter, binarizing the image, and obtaining a white pixel. It was obtained by quantifying the number of pixels of the detected fluorescent site. The porphyrin fluorescence (number of pixels) was decreased on the side where formulation example 2 containing the active ingredient yugao extract was continuously used than on the side where comparison example 2 was continuously used, and a difference between groups was observed (p < 0.05), the action of decomposing the keratotic plug by the yugao extract was shown (Table 3).

Change in porphyrin fluorescence on the cheek (pixels)

  The replica taken from the cheek was photographed under a stereoscopic microscope with the light source incident angle set to 30 degrees. The obtained image was subjected to a process of reducing noise due to bubbles or the like, and the area ratio of the pores obtained by binarization was measured, and the amount of change from before use was calculated. As a result, on the side where Formulation Example 2 containing the active ingredient yugao extract was continuously used, the pore area ratio was smaller than that on the side where Comparative Example 2 was continuously used, and a difference between groups was observed (p < 0.05), the effect of improving the conspicuousness of pores by the extract of Yugao was shown (Table 4).

Change in pore area ratio of cheek

Experimental example 4 Continuous use test 2
Formulation Example 2 (Emulsion A) containing Yugao extract, Formulation Example 8 (Emulsion B) in which a fermented solution of 0.5% pomegranate juice was added to Formulation Example 2, and Formulation Example 9 containing a fermented solution of pomegranate juice Using (Emulsion C), a one-month continuous test was performed on 18 female subjects in their 20s to 40s. A blind test was conducted in which the test subject was not informed of the presence or absence of the active ingredient. Any prescription was continuously applied to all faces of the test subject, and the test was performed twice a day, in the morning and evening, for one month. Before and after one month of continuous use, evaluation was performed using a pore score indicating the prominence of pores in the cheeks, which was taken and measured using a full-face diagnostic imaging apparatus VISIA (Canfield Scientific).

  The pore score calculated by VISIA, when the formulation example 8 containing both the fermented juice of the yugao extract and the pomegranate juice was used continuously, contained the fermented solution of the formulation example 2 containing the yugao extract and the pomegranate juice. Since the pore score was remarkably decreased as compared with the case where Formulation Example 9 was continuously used (p <0.05), the Yugao extract and the pomegranate fermented liquid were used more than the Yugao extract alone or the fermented liquid of the pomegranate juice alone. The use showed an effect of remarkably improving the conspicuousness of pores (Table 5).

Changes in cheek pore score

  The present invention provides a cathepsin V promoter, which is capable of promoting the decomposition of keratin plugs by promoting the activity of cathepsin V localized inside corn plugs, which has been clarified based on the localization of keratin plug constituent proteins. An activity promoter and an agent for improving the visibility of pores can be provided.

Claims (2)

A cathepsin V activity enhancer containing an extract of water of a gourd fruit with water and / or alcohol (however, a gouga does not contain a gangan, and uses are excluding whitening). A keratotic plug reducing agent characterized by containing a water extract of yugao fruit (however, yugao does not contain gangan, and uses other than whitening).