Skin barrier function enhancer

Abstract

This invention provides a skin barrier function enhancer that is excellent at improving skin condition, and in particular contributes to improving skin barrier function. [Solution] The skin barrier function enhancer to which the present invention is applied has the following composition. Note that the amount of each component is the weight ratio based on the total amount in the skin barrier function enhancer. Water-soluble Lithospermum erythrorhizon extract: 0.005% Oil-soluble Lithospermum erythrorhizon extract: 0.005% Vitamin B6 (Pyridoxine dicaprylate): 0.0001% Vitamin B7 (Biotin): 0.0001% Vitamin B12 (cyanocobalamin): 0.0001% Furthermore, water-soluble Lithospermum extract is a characteristic component that promotes the expression of genes involved in the biosynthesis of involucrin, filaggrin, and ceramide.

Description

Technical Field

[0001] The present invention relates to a skin barrier function promoter. Specifically, it relates to a skin barrier function promoter that has an excellent effect of improving the skin condition and particularly contributes to the improvement of the skin barrier function.

Background Art

[0002] The skin is exposed to various factors that lead to morphological changes. For example, rough skin occurs due to external factors such as dryness and irritating substances like ultraviolet rays, or internal factors such as hormonal imbalance.

[0003] In addition, rough skin is accompanied by phenomena such as a decrease in the skin barrier function, a decrease in the amount of moisture in the stratum corneum, an acceleration of epidermal turnover, and coarsening of the cutin. <s

[0004] Moreover, the stratum corneum, which is the outermost layer of the outermost epidermis that constitutes the skin, plays a role in protecting the body from external stimuli and dryness and retaining the moisture of the skin.

[0005] This stratum corneum is formed from keratinocytes formed by the terminal differentiation of epidermal keratinocytes and intercellular lipids that fill the spaces between cells. In addition, intercellular lipids mainly composed of ceramides form a lamellar structure and play a skin barrier function.

[0006] In addition, multiple proteins (enzymes) are involved in the skin barrier function of the stratum corneum. For example, involucrin, filaggrin, and the above-mentioned ceramides are present.

[0007] Here, involucrin is a precursor protein synthesized in the spinous layer of the epidermis and is a component of the "cornified envelope (CE)", which is important in the construction of the skin barrier, and forms a firm structure of the cornified envelope.

[0008] The cornified envelope, by covering the outermost layer of stratum corneum cells, plays a barrier function that prevents the invasion of external stimuli, allergens, and microorganisms, and suppresses water evaporation.

[0009] Furthermore, filaggrin is a protein cleaved from its precursor (profilaggrin) present in keratohyalin granules, and it plays a role in aggregating keratin filaments between stratum corneum cells during the keratinization process.

[0010] This filaggrin ensures the structural stability of the stratum corneum by aggregating keratin fibers, and furthermore, the degradation products of filaggrin (amino acids, pyrrolidone carboxylic acid, etc.) contribute to the skin's moisture retention as natural moisturizing factors (NMF).

[0011] Furthermore, as mentioned above, ceramides are a major component of intercellular lipids and are essential for the skin barrier's functions of moisture retention and protection against external stimuli.

[0012] In this context, a technology has been proposed that attempts to improve skin barrier function by promoting the production of proteins related to skin barrier function (see, for example, Patent Document 1).

[0013] In the involucrin production promoter described in Patent Document 1, one or more of glycine, alanine, and serine, or more specifically, arginine and one or more of glycine, alanine, and serine, are combined as active ingredients to promote involucrin production. [Prior art documents] [Patent Documents]

[0014] [Patent Document 1] Japanese Patent Publication No. 2014-185141 [Overview of the Initiative] [Problems that the invention aims to solve]

[0015] However, the involucrin production promoter disclosed in Patent Document 1 is a technology that focuses only on involucrin among several proteins involved in skin barrier function. Therefore, there was room for improvement in terms of further enhancing skin barrier function by promoting the production of other proteins involved in skin barrier function.

[0016] This invention was conceived in view of the above points, and aims to provide a skin barrier function enhancer that has excellent effects in improving skin condition, and in particular contributes to improving skin barrier function. [Means for solving the problem]

[0017] The inventors have been diligently investigating the use of Shikon extract, an active ingredient extracted from the root of the medicinal plant Lithospermum erythrorhizon Siebold et Zuccarini (Boraginaceae), and have discovered a technology that utilizes this Shikon extract to contribute to improving the skin barrier function.

[0018] To achieve the above objective, the skin barrier function enhancer of the present invention is configured to contain water-soluble Lithospermum erythrorhizon extract.

[0019] Here, by including water-soluble Lithospermum extract, it is possible to promote the expression of genes involved in the biosynthesis of involucrin, filaggrin, and ceramide. The water-soluble shikon extract referred to here is the extract obtained from the shikon extract, which is derived from the root of the shikon plant (Lithospermum erythrorhizon), specifically the water-soluble components.

[0020] Furthermore, when the water-soluble Lithospermum extract content is within the range of 0.005% to 0.5% of the total amount of skin barrier function enhancers, it can further promote the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide.

[0021] In addition, when containing oil-soluble shikon extract, vitamin B6, vitamin B7, and vitamin B12, it is possible to further promote the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide. The oil-soluble shikon extract referred to here is an extract extracted as an oil-soluble component from the shikon extract extracted from shikon, which is the root of purple gromwell.

[0022] In addition, when the content of water-soluble shikon extract and oil-soluble shikon extract is 0.005% based on the total amount of the skin barrier function promoter, and the contents of vitamin B6, vitamin B7, and vitamin B12 are within the range of 0.000001% - 0.001% based on the total amount of the skin barrier function promoter, it is possible to more sufficiently promote the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide.

[0023] In addition, when the contents of vitamin B6, vitamin B7, and vitamin B12 are within the range of 0.00001% - 0.0001% based on the total amount of the skin barrier function promoter, it is possible to more sufficiently promote the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide while setting the contents of vitamin B6, vitamin B7, and vitamin B12 at relatively low blending amounts.

[0024] In addition, when improving the production ability of involucrin, filaggrin, and ceramide, it is possible to sufficiently improve the skin barrier function by enhancing the production ability of a plurality of major proteins among the proteins involved in the skin barrier function of the stratum corneum.

Effects of the Invention

[0025] The skin barrier function promoter according to the present invention is excellent in the effect of improving the skin condition, and particularly contributes to the improvement of the skin barrier function.

Brief Description of the Drawings

[0026]

Figure 1

Figure 2

Figure 3

[0027] The following describes the composition of a skin barrier function enhancer, which is an example of a skin barrier function enhancer to which the present invention is applied.

[0028] (Embodiments of the present invention) The skin barrier function enhancer described herein has the following composition. The amounts of each component are weight ratios based on the total amount of the skin barrier function enhancer. Water-soluble Lithospermum erythrorhizon extract: 0.005% Oil-soluble Lithospermum erythrorhizon extract: 0.005% Vitamin B6 (Pyridoxine dicaprylate): 0.0001% Vitamin B7 (Biotin): 0.0001% Vitamin B12 (cyanocobalamin): 0.0001%

[0029] Furthermore, this skin barrier function enhancer can be prepared by mixing water-soluble lithospermum extract and oil-soluble lithospermum extract with various raw materials in the above-mentioned proportions to form a composition. That is, in the present invention, the water-soluble lithospermum extract and oil-soluble lithospermum extract are each formulated to make up 0.005% of the total amount in the skin barrier function enhancer.

[0030] Water-soluble Lithospermum extract is a characteristic component that promotes the expression of genes involved in the biosynthesis of involucrin, filaggrin, and ceramide.

[0031] Furthermore, water-soluble lithospermum extract is a water-soluble component extracted from lithospermum, the root of the Lithospermum plant, using ethanol and 1,3-butylene glycol (1,3-BG).

[0032] Here, the amount of water-soluble Lithospermum extract included in the skin barrier function enhancer is not necessarily limited to 0.005% of the total amount. However, in order to effectively promote the expression of genes involved in the biosynthesis of involucrin, filaggrin, and ceramide, it is preferable that it be included in the total amount of the skin barrier function enhancer within the range of 0.005% to 0.5%, and more preferably at 0.005%.

[0033] Furthermore, oil-soluble Lithospermum extract is a characteristic component that promotes the expression of genes involved in the biosynthesis of involucrin, filaggrin, and ceramide.

[0034] Furthermore, oil-soluble lithospermum extract is an oil-soluble component extracted from lithospermum, the root of the Lithospermum plant, using squalane.

[0035] Here, the amount of oil-soluble Lithospermum extract is not necessarily limited to 0.005% of the total amount of the skin barrier function enhancer. However, it is preferable that its amount be 0.005% of the total amount of the skin barrier function enhancer, as it effectively promotes the expression of genes involved in the biosynthesis of involucrin, filaggrin, and ceramide.

[0036] Furthermore, vitamin B6 (pyridoxine dicaprylate), when combined with water-soluble lithospermum extract, oil-soluble lithospermum extract, vitamin B7, and vitamin B12, is a characteristic component in skin barrier function enhancers that synergistically promotes the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide.

[0037] Furthermore, pyridoxine dicaprylate is a type of oil-soluble vitamin B6 derivative, which is stabilized by derivatizing water-soluble vitamin B6 and has the effect of enhancing absorption into the skin.

[0038] Here, the amount of vitamin B6 (pyridoxine dicaprylate) is not necessarily limited to 0.0001% of the total amount of the skin barrier function enhancer. However, in order to effectively promote the expression of genes involved in the biosynthesis of involucrin, filaggrin, and ceramide, it is preferable that it be included in the range of 0.000001% to 0.001% of the total amount of the skin barrier function enhancer, and it is even more preferable that it be included in the range of 0.00001% to 0.0001%.

[0039] Furthermore, since vitamin B6 (pyridoxine dicaprylate) is an oil-soluble component and may precipitate when mixed with water-soluble components, it is preferable that its amount in the skin barrier function enhancer be 0.001% or less of the total amount.

[0040] Furthermore, vitamin B7 (biotin), when combined with water-soluble lithospermum extract, oil-soluble lithospermum extract, vitamin B6, and vitamin B12, is a characteristic component in skin barrier function enhancers that synergistically promotes the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide.

[0041] Furthermore, vitamin B7 (biotin) is a type of water-soluble vitamin B that promotes skin cell turnover and contributes to maintaining healthy skin.

[0042] Here, the amount of vitamin B7 (biotin) in the skin barrier function enhancer is not necessarily limited to 0.0001% of the total amount. However, in order to effectively promote the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide, it is preferable that it be included in the total amount of the skin barrier function enhancer within the range of 0.000001% to 0.001%, and even more preferable that it be included in the range of 0.00001% to 0.0001%.

[0043] Furthermore, even if the amount of vitamin B7 (biotin) included in the skin barrier function enhancer exceeds 0.001% based on the total amount, the effect of promoting gene expression involved in the biosynthesis of involucrin and other genes plateaus. Additionally, since skin irritation is ensured and it exhibits high safety even for sensitive skin and infant skin, it is preferable that the amount of vitamin B7 (biotin) included in the skin barrier function enhancer is 0.001% or less based on the total amount.

[0044] Furthermore, vitamin B12 (cyanocobalamin), when combined with water-soluble lithospermum extract, oil-soluble lithospermum extract, vitamin B6, and vitamin B12, is a characteristic component in skin barrier function enhancers that synergistically promotes the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide.

[0045] Furthermore, vitamin B12 (cyanocobalamin) is a type of water-soluble vitamin B that has the effect of alleviating skin inflammation, promoting skin cell turnover, and contributing to the maintenance of healthy skin.

[0046] Here, the amount of vitamin B12 (cyanocobalamin) in the skin barrier function enhancer is not necessarily limited to 0.0001% of the total amount. However, in order to effectively promote the gene expression involved in the biosynthesis of involucrin, filaggrin, and ceramide, it is preferable that it be included in the total amount of the skin barrier function enhancer within the range of 0.000001% to 0.001%, and even more preferable that it be included in the range of 0.00001% to 0.0001%.

[0047] Furthermore, vitamin B12 (cyanocobalamin) is a pigment component that has a dark red or pink color, and when mixing skin barrier function enhancers with cosmetics, it becomes difficult to ensure a transparent or white color in the cosmetics. Therefore, it is preferable that its amount in the total amount of skin barrier function enhancers be 0.001% or less.

[0048] Furthermore, this skin barrier function enhancer can be used as an ingredient in cosmetics. It can be mixed with various raw materials to construct cosmetics.

[0049] Here, the various raw materials used in cosmetics include, for example, bases such as purified water, humectants (including oils), softeners, surfactants, pH adjusters, thickeners, neutralizing agents, plant extracts and additives, preservatives, and characteristic ingredients.

[0050] Furthermore, the various ingredients listed here are merely examples, and other components and different proportions can be appropriately set. For example, in addition to the above, depending on the type and use of the formulation, chelating agents (metal ion sequestering agents), astringents, disinfectants, skin activators (vitamins, amino acids and amino acid derivatives), anti-inflammatory agents, and whitening agents (arbutin, tranexamic acid, vitamin C derivatives, etc.) can be included. Fragrances and colorants can also be added as needed.

[0051] Furthermore, examples of cosmetic products include lotions, emulsions, facial cleansers, makeup removers, serums, gels, and creams.

[0052] Furthermore, the skin barrier function enhancer to which the present invention is applied can be used, for example, as a cosmetic ingredient in the form of a mixture with various raw materials, or as a cosmetic ingredient encapsulated in liposomes having an encapsulated structure.

[0053] As described above, the skin barrier function enhancer to which the present invention is applied exhibits excellent effects in improving skin condition, and in particular, contributes to improving skin barrier function. [Examples]

[0054] The following describes embodiments of the present invention.

[0055] Examples of skin barrier function enhancers to which the present invention is applied were prepared and evaluated as follows. (1) Evaluation of cell gene expression NHEK (normal human epidermal keratinocytes) were harvested from the culture flask. The cells were counted and each well of a 6-well plate was 3 × 10⁶ cells. 5 Cells were seeded to form cells. They were cultured overnight in an incubator at 37°C. The following day, the culture medium was collected, and a skin barrier function enhancer was added to the culture medium at the concentration (%) shown in Table 1 below. Comparative Example 1 in Table 1 corresponds to the control (CTR) described later.

[0056] [Table 1]

[0057] The culture medium after addition was added to each well of a 6-well plate at a rate of 2 mL, and incubated overnight at 37°C in an incubator. The following day, RNA was recovered using an RNA culture HC kit (Kurabo Industries Ltd.: RC-S2) and Quick Gene (Fujifilm Wako Pure Chemical Industries, Ltd.). cDNA was synthesized from the recovered RNA using a High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific: product number 4368814) and a thermal cycler (Astec Corporation: Astec GeneAtlas). The synthesized cDNA was mixed with the prepared primers for evaluation, and the expression levels of the genes involved in the biosynthesis of proteins (enzymes) involved in skin barrier function, as described below, were analyzed using a real-time thermal cycler.

[0058] The details of each gene whose gene expression level was evaluated are as follows:

[0059] IVL Involucrin gene: Involucrin is cross-linked by transglutaminase, forming a robust cornified envelope (CE) structure. This CE covers the outermost layer of stratum corneum cells, preventing the invasion of external stimuli, allergens, and microorganisms, and playing a barrier role in suppressing water evaporation. Promoting IVL expression directly leads to strengthening of the stratum corneum and contributes to the recovery and promotion of skin barrier function.

[0060] FLG: Filaggrin gene. Filaggrin ensures the structural stability of the stratum corneum by aggregating keratin fibers, and its degradation products (amino acids, pyrrolidone carboxylic acid, etc.) contribute to moisture retention as natural moisturizing factors (NMF). A decrease in filaggrin is associated with atopic dermatitis and dry skin, and promoting FLG expression leads to strengthening the structure of the stratum corneum, which is responsible for the skin barrier function.

[0061] SPTLC3: The SPTLC3 gene. SPTLC3 is one of the constituent subunits of the serine palmitoyltransferase (SPT) complex and is an enzyme involved in the biosynthesis of sphingolipids, particularly ceramide. SPTLC3 controls the synthesis of sphingoid bases, which are precursors to ceramide. Increased expression of SPTLC3 leads to an increase in ceramide levels, which in turn contributes to improved barrier function.

[0062] CERS3: The CERS3 gene. CERS3 is an enzyme that synthesizes ceramides containing very long-chain fatty acids (especially C24-C36), and its expression specifically increases with epidermal differentiation. The very long-chain ceramides produced by CERS3 are essential for the formation of the stratum corneum lipid lamellar structure. This lamellar structure is the core of the skin barrier, responsible for moisture retention and blocking external invading factors, and improved CERS3 activity promotes the maturation of the skin barrier structure. Furthermore, significant skin dryness and barrier dysfunction have been reported in CERS3-deficient mice, suggesting the importance of this enzyme in skin barrier function.

[0063] The results are shown in Figure 1. The vertical axis (relative value) in Figure 1 represents each of the four genes mentioned above. IVL For FLG, SPTLC3, and CERS3, the gene expression levels are shown as the ratio of the signal value to the expression level of the control (CTR: sample without water-soluble Lithospermum extract), with the control being set to 1. The results are shown for each gene in the samples to which Examples 1-4 were added. Furthermore, in Figure 1, and in Figures 2 and 3 described later, the four graphs corresponding to each sample are shown from left to right. IVLThis shows the gene expression levels of FLG, SPTLC, and CERS3.

[0064] As shown in Figure 1, in all of Examples 1 to 4, each of the four genes ( IVL Increased gene expression levels were observed for FLG, SPTLC3, and CERS3 compared to the control (CTR). In particular, significant increases in gene expression levels were observed in Examples 2 and 3.

[0065] Next, using the same method as described above for evaluating cell gene expression, the skin barrier function enhancer was adjusted to the concentrations (%) shown in Tables 2 to 4 below, added to the culture medium, and evaluated. Note that Comparative Example 1 in Table 2 corresponds to the control group (CTR) described above.

[0066] [Table 2]

[0067] [Table 3]

[0068] [Table 4]

[0069] The results are shown in Figure 2. The vertical axis (relative value) in Figure 2 is the same as in Figure 1, for each of the four genes mentioned above. IVL For FLG, SPTLC3, and CERS3, the gene expression levels are shown as a ratio of the signal value to the expression level of the control (CTR: sample without water-soluble Lithospermum extract), with the ratio set to 1, for each gene in the samples to which Examples 1-4 were added.

[0070] As shown in Figure 2, in all of Examples 5 to 23, each of the four genes ( IVL Increased gene expression levels were observed for FLG, SPTLC3, and CERS3 compared to the control group (CTR).

[0071] Furthermore, as shown in Figures 2 and 3, a significant increase in gene expression was observed in each of the following: Example 8, Example 21, and Example 22, all of which had the amounts of vitamin B6, vitamin B7, and vitamin B12 equalized at 0.0001%. These examples were compared to Example 23, which did not contain vitamin B6, vitamin B7, and vitamin B12. Figure 3 is a graph showing a portion of the results from Figure 2.

[0072] Furthermore, when the expression level of the control (CTR) is set to 1, the four genes in Examples 8, 21, 22, and 23 ( IVL Table 5 shows the gene expression levels for FLG, SPTLC3, and CERS3. The values ​​in Table 5 represent the results shown in Figures 2 and 3.

[0073] [Table 5]

Claims

1. It contains water-soluble Lithospermum extract and oil-soluble Lithospermum extract, Promotes gene expression of IVL, FLG, SPTLC3, and CERS3 genes. A skin barrier function enhancer.

2. The water-soluble lithospermum extract and the oil-soluble lithospermum extract are contained in an amount of 0.005% of the total amount of the skin barrier function enhancer. A skin barrier function enhancer according to claim 1.

3. Contains vitamin B6, vitamin B7, and vitamin B12 A skin barrier function enhancer according to claim 1 or claim 2.

4. The content of vitamin B6, vitamin B7, and vitamin B12 is within the range of 0.000001% to 0.001% based on the total amount of the skin barrier function enhancer. The skin barrier function enhancer according to claim 2.

5. The content of the aforementioned vitamin B6, vitamin B7, and vitamin B12 is within the range of 0.00001% to 0.0001% based on the total amount of the skin barrier function enhancer. The skin barrier function enhancer according to claim 4.

6. To improve the production capacity of involucrin, filaggrin, and ceramide. A skin barrier function enhancer according to claim 1 or 2.

Images