Improves skin clarity, dullness, texture, and visible pores

Abstract

To provide compositions for improving skin clarity, dullness, texture, or conspicuous pores.SOLUTION: Kallikrein is one of the serine proteases. KLK5 and KLK7 in the present invention are one of the kallikrein family present in the skin, and are enzymes that have the role of exfoliating the stratum corneum by degrading corneodesmosomes, which are adhesive structures in the stratum corneum. Transglutaminase is an enzyme that forms an isopeptide bond between glutamine and lysine in proteins. Unexpected upregulation of KLK5, KLK7 and TGM1 genes was observed when Hamamelis extract, Paeonia suffruticosa extract and Prunus persica extract were combined. That is, it is an agent for improving skin clarity, dullness, texture, or conspicuous pores, characterized by containing a hamamelis extract, Paeonia suffruticosa extract, and Prunus persica extract.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an agent for improving skin clarity, dullness, texture, or the visibility of pores. [Background technology]

[0002] Aging and external stimuli such as exposure to sunlight can cause symptoms such as loss of transparency, dullness, loss of texture, visible pores, and impaired barrier function. One of the causes is abnormal formation of the epidermis, the outermost layer of the skin. Most of the epidermis is composed of keratinocytes, which divide in the lowest layer of the epidermis, mature through a process called keratinization, and ultimately form the stratum corneum, which becomes dandruff and is then shed (Non-Patent Document 1).

[0003] The stratum corneum is held together by structures called corneodesmosomes, which are degraded during the process of smearing and shedding. The serine proteases kallikrein 5 (KLK5) and KLK7 have been reported to be involved in this degradation (Non-Patent Document 2). A decrease in the production or activity of KLK5 and KLK7 is thought to impede smooth stratum corneum desquamation and lead to thickening of the stratum corneum, resulting in decreased skin clarity, dullness, poor skin texture, and more visible pores.

[0004] Furthermore, a structure in the stratum corneum called the cornified cell envelope is completed by cross-linking involucrin, loricrin, and other proteins with enzymes such as transglutaminase 1 (TGM1) (Non-Patent Document 3). The completed cornified cell envelope functions as a barrier to prevent external invasion and moisture evaporation from the body (Non-Patent Document 2). Therefore, a decrease in the production or activity of TGM1 is thought to cause a decline in the skin's barrier function.

[0005] Incidentally, it has been reported that carbonyl proteins, which are reported to accumulate in aged or sun-exposed skin, reduce the expression level of TGM1 (Patent Document 1). Furthermore, it has been reported that the expression level of KLK5 is reduced in areas with dark spots (Non-Patent Document 4), suggesting the involvement of sun exposure and reduced KLK5 expression. Furthermore, it has been reported that the expression level of KLK7 in skin decreases with aging (Patent Document 2). Therefore, enhancing the production levels of TGM1, KLK5, and KLK7 is considered to be an effective means of addressing the loss of transparency, dullness, loss of texture, reduced barrier function, and more visible pores caused by sun exposure and aging.

[0006] It has been known that thioredoxin, which is highly contained in sake extract, promotes the production of KLK7 in the skin (Patent Document 3), that rosemary extract promotes KLK7 activity and promotes stratum corneum exfoliation (Patent Document 4), and that horse chestnut extract increases KLK5, promotes stratum corneum exfoliation, and leads to clearer skin (Non-Patent Document 4). It is already known that peaches and moutan pisa have the effect of promoting TGM production, and that the combination of peony, peach, and perilla has the effect of promoting KLK7 production (Patent Documents 5 to 7). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Patent Publication No. 2021-038168 [Patent Document 2] Japanese Patent Application Laid-Open No. 2013-174608 [Patent Document 3] Japanese Patent Application Laid-Open No. 2016-3198 [Patent Document 4] Japanese Patent Publication No. 2020-111540 [Patent Document 5] Patent Publication No. 2021-31417 [Patent Document 6] Japanese Patent Application Laid-Open No. 2008-7411 [Patent Document 7] Japanese Patent Application Laid-Open No. 2015-143205 [Non-patent literature]

[0008] [Non-Patent Document 1] Shimizu Hiroshi (2011) New Dermatology, 2nd Edition, Page 3 [Non-patent document 2] Journal of the Japan Cosmetic Science Society, Vol.38, No.1, pp22-27(2014) [Non-patent document 3] Shimizu, Hiroshi (2011) New Dermatology, 2nd Edition, pages 8-9 [Non-patent document 4] Fujifilm Corporation, news release dated November 24, 2020 Summary of the Invention [Problem to be solved by the invention]

[0009] An object of the present invention is to provide an agent for improving skin clarity, dullness, texture, and conspicuous pores. [Means for solving the problem]

[0010] As a result of extensive research, the inventors have found that combining witch hazel extract, moutan pisi extract, and peach extract unexpectedly increases the expression of KLK5, KLK7, and TGM1 genes, and have discovered that combining these extracts can be expected to improve skin clarity, dullness, texture, or the visibility of pores, thereby completing the present invention.

[0011] That is, the present invention provides: (1) A skin clarity, dullness, texture, or pore visibility improving agent, characterized by containing witch hazel extract, moutan extract, and peach extract; (2) The improving agent according to claim 1, which promotes stratum corneum peeling. (3) A promoter for KLK5, KLK7 or TGM1 production, characterized by containing witch hazel extract, moutan pisi extract, and peach extract; is. [Effects of the Invention]

[0012] The present invention can provide an agent for improving skin clarity, dullness, texture, or the visibility of pores, as well as an agent for promoting KLK5, KLK7, or TGM1 production. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 1 is a graph showing the effects of witch hazel extract, moutan pisi extract, and peach extract alone, as well as a mixture of these components, on KLK5 gene expression in epidermal keratinocytes in a test example. [Figure 2] FIG. 2 is a graph showing the effects of witch hazel extract, moutan pisi extract, and peach extract alone, as well as a mixture of these components, on KLK7 gene expression in epidermal keratinocytes in a test example. [Figure 3] FIG. 3 is a graph showing the effects of witch hazel extract, moutan pisi extract, and peach extract alone, as well as a mixture of these components, on TGM1 gene expression in epidermal keratinocytes in a test example. DETAILED DESCRIPTION OF THE INVENTION

[0014] The witch hazel extract in the present invention is an extract obtained from the leaves of witch hazel (scientific name: Hamamelis virginiana), the moutan quince extract is an extract obtained from the root bark of moutan quince (scientific name: Paeonia suffruticosa), and the peach extract is an extract obtained from the leaves of peach (scientific name: Prunus persica).

[0015] In the present invention, the term "transparent skin" refers to a state in which the skin color appears beautiful due to the light reflected from the surface of the skin and the light reflected from inside the skin. In the present invention, dull skin refers to a condition that occurs on the entire face, around the eyes, or cheeks, in which the redness of the skin decreases and the yellowness increases, the skin becomes less shiny, and shadows appear due to unevenness on the skin surface, resulting in a decrease in brightness and a dark appearance. The skin texture in the present invention refers to the surface pattern determined by shallow linear grooves that run regularly on the skin surface and polygons (skin areas) defined by these grooves.

[0016] In the present invention, conspicuous skin pores refer to a state in which pores become noticeable due to an increase in the area of ​​pores on the skin surface, an elongated shape of pores, or an accumulation of keratinized matter that causes the pores to turn blackish-brown.

[0017] Improvement in the present invention means making a certain state better or preventing a certain state from becoming worse.

[0018] Kallikrein is a type of serine protease. KLK5 and KLK7 in the present invention are members of the kallikrein family present in skin and are enzymes that decompose the stratum corneum by degrading corneodesmosomes, which are the adhesive structures of the stratum corneum. By promoting the activity of KLK5 and KLK7, which decompose the stratum corneum, skin clarity, dullness, texture, and visible pores can be improved.

[0019] Transglutaminase is an enzyme that forms an isopeptide bond between glutamine and lysine in proteins. TGM1 in the present invention is a member of the transglutaminase family present in skin, and is involved in the formation of the cornified cell endorope structure in the epidermis by cross-linking involucrin, loricrin, etc.

[0020] In the present invention, promotion of KLK5, KLK7 or TGM1 production refers to enhanced expression of KLK5, KLK7 or TGM1 mRNA or protein.

[0021] Commercially available products of the witch hazel extract used in the present invention include witch hazel extract BG-J (manufactured by Maruzen Pharmaceuticals), commercially available products of the moutan quince extract include moutan quince extract BG (manufactured by Maruzen Pharmaceuticals), and commercially available products of the peach extract include Yamanashi peach leaf extract BG30 (manufactured by Maruzen Pharmaceuticals).

[0022] The witch hazel extract, moutan quince extract, and peach extract used in the present invention are extracted with a solvent containing a polyhydric alcohol (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.). In addition to the polyhydric alcohol, water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), lower aliphatic ketones (acetone, etc.), etc. may also be contained. Of these, extraction with a mixture of a polyhydric alcohol and water is most preferred. Preferred examples of the polyhydric alcohol include 1,3-butylene glycol and propylene glycol, with 1,3-butylene glycol being most preferred. When extraction is performed with a solvent consisting of water and 1,3-butylene glycol, the content of 1,3-butylene glycol in the solvent is preferably 30 to 70% by volume.

[0023] The dosage form is not particularly limited, but includes external use and internal use, preferably external use by application to the skin. When the present invention is applied externally, examples of the dosage form include lotions, liquids, creams, ointments, gels, sprays, shampoos, conditioners, soaps, etc. When the present invention is applied internally, examples of the dosage form include tablets, powders, granules, liquids, capsules, dry syrups, jellies, liquid foods, semi-solid foods, solid foods, etc.

[0024] These can be produced by known methods. During production, various additives that can be contained in cosmetics, quasi-drugs, pharmaceuticals, foods and beverages, or reagents can be blended within a range that does not impair the effects of the present invention.

[0025] The present invention significantly promotes the expression of KLK5, KLK7, or TGM1 in the epidermis by combining a witch hazel extract, a moutan extract, and a peach extract. Therefore, the combination of a witch hazel extract, a moutan extract, and a peach extract of the present invention significantly promotes the expression of the stratum corneum exfoliating enzyme KLK5 or KLK7, effectively contributing to the improvement of skin clarity, dullness, texture, or the visibility of pores through stratum corneum exfoliation. Alternatively, the combination can be used as a reagent for promoting the production of KLK5, KLK7, or TGM1, and is preferably utilized as a positive control agent when conducting material screening, etc.

[0026] The fact that the present invention is for improving skin clarity, dullness, texture, or the visibility of pores, and that it is a production promoter of KLK5, KLK7, or TGM1, can be determined by the product name, the labeling on the product itself, container, or packaging, or by explanations given on product posters, television commercials, in-store POPs, information sessions, etc.

[0027] When provided as cosmetics, quasi-drugs, pharmaceuticals, food and beverages, or reagents, the contents of the witch hazel extract, moutan quince extract, and peach extract of the present invention are each in a blending ratio of 0.000001 to 10% by mass, preferably 0.0001 to 5% by mass, and more preferably 0.001 to 1% by mass, relative to the total composition. [Example]

[0028] (Test Example 1) Evaluation of changes in KLK5, KLK7, and TGM1 gene expression in epidermal keratinocytes Epidermal keratinocytes (Kurashiki Boseki) were cultured in Humedia-KG2 medium (Kurashiki Boseki, supplemented with the attached supplements) at 2500 cells / cm 2The cells were seeded into 12-well plates at a concentration of 0.33 v / v% and cultured in an incubator set at 37°C and 5% CO2. The following day, the medium was aspirated and the cells were cultured for an additional two days. On the third day after seeding, the medium was replaced with one containing the test substance and cultured for an additional day. For the extract-only group, the test substance was dissolved in the medium at a concentration of 0.33 v / v%. For the mixture group, the extracts were mixed at a weight ratio of 1:1:1 and dissolved in the medium at a concentration of 1.0 v / v%. After culture, the medium was removed, and the cells were lysed by adding lysate buffer, and the cell lysate was collected. RNA was extracted from the cell lysate using the RNeasy Mini Kit (Qiagen) according to the attached protocol. cDNA was synthesized using this as a template by reverse transcription using Prime Script RT Master mix (Takara Bio). The mRNA expression levels of RPLP0, KLK5, KLK7, and TGM1 were measured (SYBR Green method) using the synthesized cDNA with a real-time PCR system (Step One Plus, Thermo Fisher Scientific). The expression levels of KLK5, KLK7, and TGM1 were normalized by the expression level of RPLP0. The following primers were used: RPLP0: HA234224, KLK5: HA102824, KLK7: HA198521, and TGM1: HA171645 (all Takara Bio). The measured mRNA expression levels were compared with those of a control group (medium not containing the test substance) to evaluate the effects of the test substance on KLK5, KLK7, and TGM1 gene expression.

[0029] <Test Results> The results are shown in Figures 1 to 3. In the extract-only group, no changes in gene expression were observed compared to the control group. On the other hand, in the mixture group, a significant increase in the expression level of each gene was observed, even though the concentration of each extract was the same as in the extract-only group (0.33 v / v%). It is believed that mixing the extracts produced an unexpected effect of increasing gene expression. Therefore, the mixture of witch hazel extract, moutan pisi extract, and peach extract is useful as an agent for improving skin clarity, dullness, texture, or the appearance of pores, or as a positive control agent when screening for ingredients that promote KLK5, KLK7, or TGM1 expression. <Formulation example: Lotion> JPEG0007782167000001.jpg7378 [Industrial Applicability]

[0030] The KLK5, KLK7 or TGM1 production promoter of the present invention, which is characterized by containing witch hazel extract, moutan quince extract and peach extract, can be used, for example, as a reagent for improving skin symptoms such as transparency, dullness, texture or visible pores, or for promoting KLK5, KLK7 or TGM1 expression, and can preferably be used as a positive control drug when performing material screening, etc.

Claims

1. The agent for improving skin clarity, dullness, texture, or conspicuous pores is characterized by containing a witch hazel extract, a moutan extract, and a peach extract.

2. A stratum corneum peeling promoter characterized by containing witch hazel extract, moutan quince extract, and peach extract.

3. A KLK5, KLK7 or TGM1 production promoter, characterized by containing witch hazel extract, moutan pi extract, and peach extract.

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