Keratin 79 expression promoter and acne treatment agent

Abstract

This invention provides a novel keratin 79 expression promoter that is naturally derived and capable of promoting the expression of keratin 79 in the skin. [Solution] A keratin 79 expression promoter containing an extract of Swertia japonica as an active ingredient, preferably containing water and / or ethanol, and preferably adjusted so that the concentration of the extract is 0.1 to 5% by mass.

Description

Technical Field

[0001] The present invention relates to a keratin 79 expression promoter that promotes keratin 79 expression in the skin and an acne-improving agent.

Background Art

[0002] Acne (acne vulgaris) is an inflammatory skin disease that develops when sebum accumulates in hair follicles (pores) and causes inflammation. Rashes are observed corresponding to the pores mainly on the face, chest, back, etc. Acne is caused mainly by Cutibacterium acnes. Since Cutibacterium acnes is an anaerobic bacterium, it lives deep in the pores and grows using sebum accumulated in the pores as a nutrient source. Pores clogged with sebum like this are called comedones.

[0003] As compositions for treating acne, compositions containing adapalene or benzoyl peroxide have been proposed (see Non-Patent Documents 1 and 2). However, when using adapalene or benzoyl peroxide, there is a possibility of causing side reactions such as a feeling of irritation, erythema, and dryness on the skin. In order to avoid these side reactions, it is desirable to use natural-derived products.

[0004] Normally, in skin not suffering from acne, keratin 79 is expressed from the junction of the hair follicle (pore) and the sebaceous gland to the infundibulum of the pore. However, it has been reported that abnormal differentiation of sebaceous gland cells occurs in the pores of the skin of patients suffering from acne (see Non-Patent Document 3), and it has also been reported that the expression level of keratin 79 is decreased (see Non-Patent Document 4). Therefore, if the expression level of keratin 79 can be increased, in patients suffering from acne, the already developed acne can be reduced (treated), and in those not suffering from acne, the occurrence of acne can be suppressed (prevented). However, no studies have been made on natural-derived products that can increase the expression level of keratin 79.

[0005] On the other hand, Swertia japonica extract (extract from Swertia japonica) is taken orally as a bitter stomachic and intestinal regulator, while also being incorporated into topical skin preparations as a blood circulation promoting ingredient (see Patent Document 1). Thus, Patent Document 1 uses Swertia japonica extract to promote blood circulation, and does not show any relationship between acne and Swertia japonica extract. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] Japanese Patent Publication No. 2014-84304 [Non-patent literature]

[0007] [Non-Patent Document 1] Adapalene® Gel and Differin® Gel 0.1% (Medical Drug Interview Form, Revised January 2023, 14th Edition) [Non-Patent Document 2] Acne vulgaris treatment agent: Benzoyl peroxide preparations: BEPIO® Gel 2.5%, BEPIO® Lotion 2.5%. Pharmaceutical Interview Form, revised July 2024 (13th edition). [Non-Patent Document 3] Jean-Hilaire Saurat, “Strategic Targets in Acne:The Comedone Switch in Question”, Dermatology, Karger AG, 2015;231:105-111 [Non-Patent Document 4] Natalia A. Veniaminova et al, “Keratin 79 identifies a novel population of migratory epithelial cells that initiates hair canal morphogenesis and regeneration”, Development, The Company of Biologists Ltd, (2013) 140, P. 4870-4880 [Overview of the Initiative] [Problems that the invention aims to solve]

[0008] In view of the above circumstances, the present invention aims to provide a novel keratin 79 expression promoter that is naturally derived and capable of promoting the expression of keratin 79 in the skin, and a novel acne treatment agent that is naturally derived and capable of improving acne by promoting the expression of keratin 79 in the skin. [Means for solving the problem]

[0009] The characteristic configuration of the keratin 79 expression promoter according to the present invention, which solves the above problems, is as follows: The key feature is that it contains an extract of Swertia japonica as an active ingredient.

[0010] This keratin 79 expression promoter contains a naturally derived extract of Swertia japonica as an active ingredient, thereby promoting the expression of keratin 79. When this keratin 79 expression promoter is applied to the skin, the amount of keratin 79 expressed in the stratum corneum of the skin increases, which can reduce the size of comedones, thus treating acne. Furthermore, it can suppress the formation of comedones, thus preventing acne.

[0011] In the keratin 79 expression promoter according to the present invention, It is preferable that the product contains water and / or ethanol.

[0012] According to the keratin 79 expression promoter of this configuration, by containing water and / or ethanol, it is possible to suppress skin damage caused by the solvent and to form a dosage form such as an extract that is easy to handle.

[0013] In the keratin 79 expression promoter according to the present invention, It is preferable that the concentration of the extract is adjusted to be 0.1 to 5% by mass.

[0014] According to the keratin 79 expression promoter of this configuration, by adjusting the concentration (content) of the extract to be within the above appropriate range and directly contacting the skin cells, it is possible to suppress damage such as cytotoxicity and further promote the expression of keratin 79.

[0015] In the keratin 79 expression promoter according to the present invention, It is preferably for improving acne.

[0016] According to the keratin 79 expression promoter of this configuration, by using it for improving acne, the functions of the keratin 79 expression promoter can be more effectively exerted.

[0017] Another characteristic configuration of the acne improving agent according to the present invention for solving the above problems is containing an extract of assembly as an active ingredient.

[0018] According to the acne improving agent of this configuration, as described above, by containing an extract of assembly, which is naturally derived, as an active ingredient, it is possible to promote the expression of keratin 79. By applying such an acne improving agent to the skin, the expression level of keratin 79 in the stratum corneum of the skin increases, so that the generated comedones can be reduced. As a result, acne can be treated, and the occurrence of comedones can be suppressed. As a result, acne can be prevented.

Brief Description of the Drawings

[0019] [Figure 1]Figure 1 is a photograph of the left and right cheeks of a subject who confirmed the expression level of keratin 79 in the skin. [Figure 2] Figure 2 is a diagram showing the confirmation results of the expression level of keratin 79 in the skin. [Figure 3] Figure 3 is a graph showing the confirmation results of the expression level of keratin 79 in the skin. [Figure 4] Figure 4 is a graph showing a partial extract of the results of a screening experiment of plant extracts that can promote the expression of keratin 79 in the skin.

Mode for Carrying Out the Invention

[0020] The inventors of this invention have conducted diligent research and have found the following: As mentioned above, acne occurs when sebum clogs pores and comesdones (blackheads / whiteheads) are formed. When observing the skin of patients prone to acne, even when it appears normal at first glance, the frequency of comedones and even smaller microcomedones (small blackheads) is high, which is thought to be the cause of recurring acne. Therefore, in order to prevent recurring acne, it is important to suppress the formation of comedones. The formation of comedones is thought to be caused by cells that normally differentiate into sebaceous cells differentiating into epithelial cells, which clogs pores. Therefore, it is thought that whether epidermal cells differentiate into epithelial cells or sebaceous cells is the branching point for comedone formation. Considering this finding together with the fact that, as described in Non-Patent Documents 3 and 4 above, the expression level of keratin 79, a type of protein, is reduced in the pores of acne-prone patients due to abnormal differentiation of sebaceous gland cells, it is thought that keratin 79 may be involved in comedone formation. Specifically, it is believed that skin prone to acne has a low expression level of keratin 79 in the stratum corneum, while skin less prone to acne has a high expression level of keratin 79. To find an active ingredient that can increase the expression level of keratin 79 from naturally derived products with low skin irritation, we screened extracts from 165 different plants. As a result, we found that Swertia japonica extract can significantly promote the expression of keratin 79, thereby preventing or treating acne, and thus completed the present invention.

[0021] The keratin 79 expression promoter and acne treatment agent of the present invention will be described below. However, the present invention is not intended to be limited to the configurations described in the embodiments below. In this specification, when a numerical range is indicated by "~", it means that the numerical values ​​enclosing "~" are included as the upper and lower limits, and the numerical range may be formed by appropriately combining the upper and lower limits. In this specification, "acne treatment" means treating acne and / or preventing acne.

[0022] [Keratin 79 expression promoter] The keratin 79 expression promoter contains Swertia japonica extract as an active ingredient. The keratin 79 expression promoter can promote the expression of keratin 79 in human skin. The keratin 79 expression promoter is preferably a liquid extract, but may contain only Swertia japonica extract.

[0023] <Keratin 79> Keratin 79 is a protein that is normally expressed in the junction of the hair follicle (pore) and sebaceous gland, extending from the infundibulum of the pore, in skin that is not affected by acne. In the pores of patients with acne, abnormalities occur in the differentiation of sebaceous gland cells, and the expression level of keratin 79 is reduced. However, by increasing the expression level of keratin 79, it is possible to reduce (treat) existing acne in patients with acne, and to suppress (prevent) the development of acne in people who are not affected by acne.

[0024] <Swertia japonica extract> Swertia japonica (Schult.) Makino is a biennial plant belonging to the genus Swertia in the Gentianaceae family, distributed from China and the Korean Peninsula to Japan, and is used as a medicinal herb. Any part of the plant, such as the flowers, leaves, stems, or roots, can be used for extraction, but it is preferable to use the whole plant (including the flowers, leaves, stems, and roots). Swertia extract can be obtained by coarsely grinding the parts to be used by finely chopping or pulverizing them, and then extracting them with an extraction solvent such as water, ethanol (including anhydrous ethanol), or a mixture thereof.

[0025] The keratin 79 expression promoter may contain, in addition to the active ingredient, Swertia japonica extract, water or an organic solvent such as ethanol as described above for dissolving or diluting it. In other words, the keratin 79 expression promoter may contain water and / or ethanol in addition to the Swertia japonica extract. The extraction solvent described above may be used as is as the solvent to be included in the keratin 79 expression promoter.

[0026] <Concentration (content) of Swertia japonica extract> When the keratin 79 expression promoter is an extract, the concentration of Swertia japonica extract in the keratin 79 expression promoter can be appropriately set to a concentration that can promote keratin 79 expression in the skin. For example, it is preferable that the concentration of Swertia japonica extract in the keratin 79 expression promoter be adjusted to 0.1 to 5% by mass. Furthermore, by adjusting the concentration (content) of Swertia japonica extract in the keratin 79 expression promoter to be within the above appropriate range, it is possible to further promote keratin 79 expression while suppressing cytotoxicity by directly contacting skin cells. For example, the keratin 79 expression promoter can be a mixture of 1.3% by mass of Swertia japonica extract, 69.09% by mass of ethanol, and 29.61% by mass of water.

[0027] The keratin 79 expression promoter contains a naturally derived extract of Swertia japonica as an active ingredient, thereby promoting the expression of keratin 79. By applying this keratin 79 expression promoter to the skin, the amount of keratin 79 expressed in the stratum corneum of the skin increases, which can reduce the size of comedones, thus treating acne. Furthermore, it can suppress the formation of comedones, thus preventing acne.

[0028] Keratin 79 expression promoters are preferably used for acne treatment. By using keratin 79 expression promoters for acne treatment, the functions of the keratin 79 expression promoters can be exhibited more effectively.

[0029] Furthermore, the keratin 79 expression promoter can also be used in a method to promote keratin 79 expression by contacting it with skin cells in vitro (expression promotion method), thereby enabling its use in basic research on skin cells.

[0030] [Acne treatment] The acne treatment contains Swertia japonica extract as an active ingredient. The acne treatment can promote the expression of keratin 79, which is found in the stratum corneum of human skin. The acne treatment is preferably in liquid extract form, but may also contain only Swertia japonica extract.

[0031] Acne treatment agents promote the expression of keratin 79 in human skin cells and increase its expression level. This increases the amount of keratin 79 expressed in the stratum corneum of the skin, which can reduce the size of comedones that have formed, thus treating acne. Furthermore, they can suppress the formation of comedones, thus preventing acne. In this respect, acne treatment agents can be said to be the same as the keratin 79 expression promoters described above, applied to acne treatment agents. The composition of acne treatment agents is the same as that of the keratin 79 expression promoters described above, so a detailed explanation will be omitted.

[0032] As mentioned above, acne treatment agents can promote the expression of keratin 79 by containing a naturally derived extract of Swertia japonica as an active ingredient. By applying such acne treatment agents to the skin, the amount of keratin 79 expressed in the stratum corneum of the skin increases, which can reduce the size of comedones that have formed, thereby treating acne. Furthermore, it can suppress the formation of comedones, and as a result, prevent acne.

[0033] Furthermore, acne-improving agents can also be used in in vitro methods to improve acne by contacting skin cells (production promotion methods), thereby allowing them to be used in basic experiments on skin cells.

[0034] [Application form] The keratin 79 expression promoter and acne treatment agent described above can be in the form of cosmetics, pharmaceuticals, quasi-drugs, experimental reagents, etc., containing them as active ingredients.

[0035] When formulated as cosmetics, quasi-drugs, pharmaceuticals, etc., Swertia japonica extract can be incorporated into the above-mentioned forms by, for example, incorporating the keratin 79 expression promoter or the acne-improving agent described above. In addition, when formulated as cosmetics, quasi-drugs, pharmaceuticals, etc., the above-mentioned keratin 79 expression promoter and acne-improving agent, as extracts, can be appropriately combined with conventionally known ingredients used in cosmetics, quasi-drugs, and pharmaceuticals (moisturizers, solubilizers, emulsifiers, oils, drugs, thickeners, stabilizers, preservatives, etc.) to the extent that the effects of containing Swertia japonica extract are not hindered.

[0036] The amounts of the keratin 79 expression promoter and acne-improving agent in these forms can be appropriately set so that the concentration of the Swertia japonica extract in the above forms is at a level that can promote the expression of keratin 79 in the skin and prevent or suppress acne. In this case, the concentration of the Swertia japonica extract may be appropriately adjusted by appropriately removing the solvent contained in the above-mentioned keratin 79 expression promoter and acne-improving agent as extracts by reducing pressure, drying, etc. Furthermore, the amount used (applied amount) in a single application to the skin in the above forms can be appropriately adjusted so that it is an amount that can prevent or suppress acne. Therefore, the concentration of the Swertia japonica extract in the above forms can be appropriately adjusted according to the amount used in a single application. Furthermore, when used in the form of experimental reagents, the amount of the keratin 79 expression promoter and acne-improving agent in the above forms can be appropriately adjusted so that, for example, the concentration of the Swertia japonica extract after addition to cells is 0.1 to 1 mg / mL.

[0037] The above-mentioned forms can be obtained by stirring and mixing a keratin 79 expression promoter or acne treatment agent containing Swertia japonica extract with other additives as needed, using conventionally known methods. [Examples]

[0038] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0039] [Confirmation of keratin 79 expression levels in the skin] This study investigated the relationship between keratin 79 expression levels in the facial skin of human subjects and the occurrence of acne. As shown in Figure 1, the subjects were two individuals (Subject A and Subject B) who had many acne lesions on their right cheek and few on their left cheek. To minimize the influence of individual differences, comedones were collected from the right and left cheeks of the same subject using cyanoacrylate biopsy, shredded into small pieces, and then subjected to extraction buffer and protein extraction using a handheld homogenizer. After protein extraction, Western blotting was performed. The expression level of keratin 79 was evaluated by correcting for keratin 79 expression intensity and total protein amount measured by CBB (Coomasie Brilliant Blue) staining. The results are shown in Figures 2 and 3. As a result, in both Subject A and Subject B, the expression level of keratin 79 was lower on the right cheek, which had more acne lesions, than on the left cheek, which had fewer lesions.

[0040] [Screening experiment] <Evaluation of the controls> It is believed that keratin 79 expression is reduced in the hair follicles of patients with acne due to decreased TGFβ signaling. Therefore, a screening experiment was conducted to determine whether keratin 79 expression was restored after initially reducing it. Specifically, immortalized keratinocytes (PSVK1) were seeded in 12-well plates, and after 3 days of culture, CaCl2 was added to promote keratinocyte differentiation, and RepSox, a TGFβ inhibitor, was added to promote the reduction of keratin 79 expression. After a further 7 days of culture, keratinocyte RNA was extracted, and the ratio of keratin 79 (K79) to GAPDH (K79 / GAPDH) was measured by RT-qPCR. PSVK1 was used as a substitute cell for sebaceous gland cells. It was also confirmed that keratin 79 is expressed in PSVK1.

[0041] <Evaluation of extracts from various plants> Immortalized keratinocytes (PSVK1) were seeded in 12-well plates, and the ratio of keratin 79 (K79) to GAPDH (K79 / GAPDH) in each plant extract was measured in the same manner as in "Evaluation of Controls" above, except that each extract containing extracts from 165 different plants, including Swertia japonica, was added to the total contents of each well at concentrations of 0.2% by mass and 0.4% by mass, respectively. In the case of Swertia japonica extract, the concentration of Swertia japonica extract in the extract added at a concentration of 0.2% by mass was 0.026 mg / mL, and the concentration of Swertia japonica extract in the extract added at a concentration of 0.4% by mass was 0.052 mg / mL. Figure 4 shows excerpts of the results for some of the plant extracts, including Swertia japonica, out of the 165 plant extracts. Figure 4 shows the results of two repeated tests (n=2) for the concentration of each plant extract. As shown in Figure 4, Swertia japonica extract was shown to promote keratin 79 expression compared to extracts from other plants. Although not shown in the figure, Swertia japonica extract also showed a significantly increased expression of keratin 79 compared to the remaining extracts from the 165 plants mentioned above. [Industrial applicability]

[0042] The keratin 79 expression promoter and acne treatment agent of the present invention can be suitably used in cosmetics, quasi-drugs, pharmaceuticals, research and development, manufacturing, sales, and experimental reagents related thereto.

Claims

1. A keratin 79 expression promoter containing Swertia japonica extract as an active ingredient.

2. The keratin 79 expression promoter according to claim 1, which contains water and / or ethanol.

3. The keratin 79 expression promoter according to claim 1 or 2, wherein the concentration of the extract is adjusted to 0.1 to 5% by mass.

4. A keratin 79 expression promoter according to claim 1, for the purpose of improving acne.

5. An acne treatment containing Swertia japonica extract as an active ingredient.

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