Skin cell activator

Abstract

To provide a cell activator that exhibits excellent cell-activating effects even when exposed to dry conditions.SOLUTION: Japanese white birch sap fermentation products are useful as an active ingredient for cell activation, since they exhibit excellent cell-activating effects even when exposed to dry conditions. A cell activator containing not only (A) Japanese white birch sap fermentation products but also (B) Japanese white birch sap demonstrates further enhanced cell-activating effects.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a skin cell activating agent. [Background technology]

[0002] Activation of epidermal cells is an important function in normalizing the metabolism of the epidermis and thus maintaining skin homeostasis. For this reason, active ingredients as skin cell activators are being searched for. As such activators, extracts of sesame, dill, red pepper, angelica, dokudami, chinese ginger (Patent Document 1), almond, dandelion, elderberry, cnidium, swertia japonica, sohakuhi, peach kernel, carrot, hop, rose of Sharon, coix seed (Patent Document 2), ginger family, curcuma genus (Patent Document 3), and oleander family, oleander genus (Patent Document 4) are known. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 10-45615 [Patent Document 2] Japanese Patent Application Publication No. 10-36279 [Patent Document 3] JP 2004-75632 A [Patent Document 4] JP 2005-89375 A Summary of the Invention [Problem to be solved by the invention]

[0004] Conventional cell activating agents do not have sufficient effects, and excellent effects cannot be expected even when exposed to dry conditions, for example.

[0005] Therefore, an object of the present invention is to provide a cell activating agent that has an excellent skin cell activating effect even when exposed to dry conditions. [Means for solving the problem]

[0006] The present inventors have found that the fermented birch sap product has an excellent effect of activating skin cells, and that by combining the fermented birch sap product with birch sap, the effect of activating skin cells is enhanced compared to when the fermented birch sap product is used alone. The present invention was completed based on this finding and through further investigation. That is, the present invention provides the following aspects of the invention.

[0007] Item 1. (A) A skin cell activator containing fermented birch sap. Item 2. The skin cell activating agent according to Item 1, further comprising (B) birch sap. Item 3. The skin cell activating agent according to Item 2, wherein the total amount of glucose contained in the component (A) and the component (B) is 0.001 to 0.1% by weight. Item 4. The skin cell activating agent according to Item 2 or 3, comprising 0.1 to 20 parts by dry weight of the component (B) per 1 part by dry weight of the component (A). Item 5. The skin cell activating agent according to any one of Items 1 to 4, wherein the content of the component (A) is 0.005 to 1 wt % on a dry basis. Item 6. The cell activating agent according to any one of Items 1 to 5, which is used on skin exposed to an environment that dries the skin. Effect of the Invention

[0008] According to the present invention, there is provided a cell activating agent that has an excellent skin cell activating effect even when exposed to dry conditions. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] The skin cell activator of the present invention (hereinafter also simply referred to as the "cell activator") is characterized by containing (A) a fermented birch sap product (hereinafter also referred to as the "component (A)"). In a preferred embodiment of the present invention, the cell activator can further contain (B) birch sap (hereinafter also referred to as the "component (B)"). The cell activator of the present invention will be described in detail below.

[0010] (A) Fermented birch sap In the present invention, the fermented birch sap used as component (A) refers to a yeast fermentation product of birch sap.

[0011] Examples of birch, the source of birch sap, include broadly defined birch (Betula platyphylla (Betula pendula var. platyphylla)), American birch (Betula papyrifera), European birch (Betula pendula (weeping birch)), European birch (Betula pubescens (European birch)), and white birch (Betula szechuanica (Betula pendula var. szechuanica)). Specific examples of the broad-sense Japanese white birch include Betula platyphylla var. platyphylla, Betula platyphylla var. japonica, Betula platyphylla var. japonica f. laciniata, Betula platyphylla var. kamtschatica, and Betula platyphylla var. mandshurica. In addition, the classification of Japanese white birch, which is the source of Japanese white birch sap, by place of origin includes the Japanese white birch native to Hokkaido.

[0012] In the present invention, the sap of the white birch used as the raw material of component (A) may be collected from one of the above white birches, or may be collected from a combination of two or more of the above white birches. In the present invention, among the above white birches, the white birch native to Hokkaido is preferably used.

[0013] Birch sap is usually an exudation obtained by drilling a hole in the trunk of a birch tree. The composition of the birch sap, when the exudation is neither concentrated nor diluted, is about 99% by weight water, and the remaining 1% by weight organic and inorganic matter. The organic matter includes monosaccharides or disaccharides such as glucose, fructose, galactose, sucrose, etc.; polysaccharides; organic acids such as malic acid and succinic acid; amino acids such as citrulline, glutamine, glutamic acid, aspartic acid, valine, isoleucine, methionine, leucine, lysine, phenylalanine, glycine, alanine, threonine, arginine, cystine, cysteine, proline, serine, tyrosine, histidine, etc.; proteins, etc. Inorganic substances may include minerals such as calcium, potassium, sodium, magnesium, manganese, iron, zinc, phosphorus, barium, silicon, boron, lanthanum, strontium, thorium, aluminum, and chromium.

[0014] In the present invention, the birch sap used as the raw material for component (A) preferably has a glucose content of, for example, 0.05 to 2% by weight, preferably 0.06 to 1% by weight, more preferably 0.07 to 0.5% by weight, even more preferably 0.08 to 0.3% by weight, even more preferably 0.09 to 0.2% by weight, and even more preferably 0.1 to 0.15% by weight. The glucose contained in the birch sap is used as a carbon source in the preparation (fermentation) of component (A).

[0015] The birch sap used as the raw material for component (A) may be the above-mentioned exudate that has been appropriately pretreated by heat sterilization and / or filtration.

[0016] The yeast used in the production of component (A) is not particularly limited, and examples thereof include the genera Candida, Galactomyces, Saccharomycopsis, Saccharomyces, and Pichia. Specific examples of Galactomyces yeast include Galactomyces reessii, Galactomyces geotrichum, Galactomyces candidus, and Galactomyces pseudocandidus. Specific examples of yeasts belonging to the genus Saccharomycopsis include Saccharomycopsis capsularis, Saccharomycopsis crataegensis, Saccharomycopsis malanga, etc. Specific examples of yeasts belonging to the genus Saccharomyces include Saccharomyces cerevisiae, Saccharomyces bacillaris, Saccharomyces pastorianus, Saccharomyces bayanus, etc.

[0017] In the present invention, the yeast used in the production of component (A) may be one of the above yeasts alone or a combination of two or more of them. Among the above yeasts, the genus Galactomyces is preferred in the present invention, and Galactomyces raceii, Galactomyces geotrichum, Galactomyces candidus, and Galactomyces pseudocandidus are more preferred, and Galactomyces raceii is even more preferred.

[0018] Component (A) is produced by subjecting a mixed medium containing the birch sap and the yeast to conditions for yeast fermentation (alcohol fermentation) to obtain a culture of the mixed medium (yeast fermentation liquid of birch sap). The content of the birch sap in the mixed medium is, for example, 90 to 99% by weight, preferably 93 to 97% by weight.

[0019] The mixed medium may contain only the birch sap and the yeast, or may further contain a normal yeast medium in addition to these. The normal yeast medium is not particularly limited as long as it contains components necessary for yeast culture (carbon source, nitrogen source, and / or minerals, etc.). Examples of nitrogen sources include yeast extract, peptone, casein, soybean hydrolysate, malt extract, amino acids, etc., examples of carbon sources include glucose, etc., and examples of minerals include sodium, potassium, calcium, magnesium, etc. A preferred mixed medium in the present invention may not contain the carbon source and / or mineral components used in a normal yeast medium among the above components, and preferably may not contain the carbon source and mineral components used in a normal yeast medium. A particularly preferred mixed medium in the present invention contains the birch sap, the yeast, yeast extract, and peptone. The glucose content in the mixed medium is, for example, 0.04 to 2 wt%, preferably 0.05 to 1 wt%, more preferably 0.06 to 0.5 wt%, even more preferably 0.07 to 0.3 wt%, even more preferably 0.08 to 0.2 wt%, and even more preferably 0.09 to 0.14 wt%.

[0020] The degree of yeast fermentation of component (A) is not particularly limited, but is preferably such that the amount of glucose contained in the birch sap used as the raw material is consumed to 1 / 60 weight or less, preferably 1 / 80 weight or less, more preferably 1 / 100 weight or less, even more preferably 1 / 1000 weight or less, and particularly preferably such that the glucose is completely consumed. Alternatively, the degree of yeast fermentation of component (A) may be such that the amount of glucose in the mixed medium is consumed to 0.002 weight % or less, preferably 0.001 weight % or less, more preferably 0.0001 weight % or less, and even more preferably such that the glucose is completely consumed.

[0021] The component (A) is preferably a yeast fermentation liquid obtained by yeast fermentation, which is further treated under high temperature conditions. This allows useful components in the yeast cells to be extracted into the yeast fermentation liquid. The high temperature treatment conditions include, for example, 110 to 130°C, preferably 115 to 125°C, and 20 to 40 minutes.

[0022] The amount of glucose in component (A) may vary depending on the degree of yeast fermentation, but it is preferable that component (A) is substantially not contained in the composition in a liquid state that has not been concentrated or diluted after yeast fermentation (specifically, 0.04% by weight or less, preferably 0.02% by weight or less, and more preferably 0.01% by weight or less), and it is even more preferable that component (A) does not contain any glucose at all.

[0023] The component (A) may be used in a state in which the yeast fermentation liquid is neither diluted nor concentrated. However, if necessary, the yeast fermentation liquid may be used as a concentrate or dried product obtained by subjecting the yeast fermentation liquid to treatment such as concentration and drying, or as a diluted product obtained by subjecting the yeast fermentation liquid to a dilution treatment with a base such as water.

[0024] The content (in terms of dry weight) of the (A) component in the cell activating agent of the present invention is not particularly limited, and may be, for example, 0.005 to 1% by weight. From the viewpoint of further enhancing the cell activation effect, the content (in terms of dry weight) of the (A) component is preferably 0.01 to 1% by weight or 0.02 to 1% by weight, more preferably 0.025 to 1% by weight, 0.03 to 1% by weight, 0.035 to 1% by weight, 0.04 to 1% by weight, 0.045 to 1% by weight, 0.05 to 1% by weight, or 0.055 to 1% by weight. In addition, since the cell activating agent of the present invention has an excellent cell activation effect, even a relatively small amount of the (A) component can effectively exert the cell activation effect. Furthermore, when the cell activating agent of the present invention further contains the (B) component, the cell activation effect is further enhanced, and therefore even a small amount of the (A) component can effectively exert the cell activation effect. From these viewpoints, suitable examples of the content (converted into dry weight) of component (A) in the cell activating agent of the present invention include 0.005 to 0.5 wt %, 0.005 to 0.1 wt %, 0.005 to 0.07 wt %, 0.005 to 0.06 wt %, 0.005 to 0.05 wt %, 0.005 to 0.04 wt %, or 0.005 to 0.035 wt %.

[0025] (B) Birch sap In the present invention, the birch sap used as component (B) is the same as the birch sap used as the material for component (A) above. Therefore, the details of the birch from which component (B) is derived, the composition of component (B), and the pretreatments acceptable for component (B) are the same as those described for the material for component (A) above.

[0026] The blending ratio of the (B) component to the (A) component may be appropriately set depending on the desired degree of cell activation improving effect, and may be, for example, 0.1 to 20 parts by weight, 1 to 10 parts by weight, or 1.5 to 7 parts by weight in terms of dry weight of the (B) component per 1 part by weight of the dry weight of (A). From the viewpoint of further enhancing the cell activation effect, the blending ratio is preferably 1.8 to 5.3 parts by weight, or 2 to 4.5 parts by weight, more preferably 2.1 to 3.9 parts by weight, or 2.2 to 3.5 parts by weight, and even more preferably 2.3 to 3.2 parts by weight, 2.4 to 3 parts by weight, or 2.5 to 2.8 parts by weight.

[0027] The specific content (converted into dry weight) of component (B) in the cell activating agent of the present invention is determined depending on the blending amount of component (A) and the above-mentioned blending ratio, and may be, for example, 0.005 to 0.5 wt %, preferably 0.007 to 0.3 wt %, or 0.009 to 0.2 wt %, preferably 0.01 to 0.15 wt %, or 0.02 to 0.1 wt %, more preferably 0.03 to 0.095 wt %, or 0.05 to 0.09 wt %, and even more preferably 0.065 to 0.085 wt %.

[0028] Another specific content of component (B) in the cell activator of the present invention is, for example, 1 to 30% by weight, preferably 4 to 16% by weight, more preferably 8 to 12% by weight, and even more preferably 9 to 11% by weight, which is equivalent to the content of birch sap in a form in which birch exudate is neither concentrated nor diluted.

[0029] The total amount of glucose contained in component (A) and component (B) in the cell activating agent of the present invention is, for example, 0.001 to 0.1 wt %, or 0.002 to 0.05 wt %, preferably 0.003 to 0.02 wt %, or 0.004 to 0.015 wt %, more preferably 0.007 to 0.012 wt %, and even more preferably 0.008 to 0.011 wt %.

[0030] Other Ingredients In addition to the above-mentioned components, the cell activating agent of the present invention may contain, if necessary, other active ingredients other than the components (A) and (B) Such other active ingredients include melanin production inhibitors, anti-inflammatory agents, disinfectants, skin protective agents, blood circulation promoters, cooling agents, vitamins, mucopolysaccharides, antihistamines, local anesthetics, etc.

[0031] Furthermore, the cell activator of the present invention may contain a base and / or additives as necessary to obtain a desired formulation. Such bases and additives are not particularly limited as long as they are pharma- ceutically acceptable, and examples of such bases and additives include water; aqueous bases such as monohydric lower alcohols (having 1 to 5 carbon atoms) and polyhydric alcohols; oils (medium-chain fatty acid triglycerides, vegetable oils, animal oils, etc.), mineral oils, waxes or waxes, ester oils, fatty acid alkyl esters, higher (having 8 to 22 carbon atoms) fatty acids, higher (having 8 to 22 carbon atoms) fatty acid esters, higher (having 8 to 22 carbon atoms) alcohols, cholesterol, silicone oils, and other oil-based bases; nonionic surfactants (polyoxyethylene hydrogenated castor oil; sorbitan fatty acid esters; glycerin fatty acid esters; propylene glycol fatty acid esters; glycerin alkyl ethers; polyoxyethylene sorbitan fatty acid esters; polyoxyethylene sorbitan fatty acid esters; polyoxyethylene sorbitan fatty acid esters; polyoxyethylene glycerin fatty acid esters; polyoxyethylene ... oxyethylene alkyl or aralkyl ethers and their phosphoric acid or phosphate salts; surfactants such as Pluronic (registered trademark) types (e.g., Pluronic (registered trademark), polyoxyethylene-polyoxypropylene alkyl ether, etc.), anionic surfactants (alkyl sulfate ester salts, alkyl ether sulfate ester salts, N-acylsarcosinic acid, fatty acid amide sulfonate salts, sulfosuccinate salts, alkylbenzene sulfonate salts, fatty acid ester sulfate ester salts, N-acyl glutamate salts, polyoxyethylene alkyl ether carboxylic acid salts, polyoxyethylene alkyl aryl ether carboxylate salts, α-olefin sulfonate salts, etc.); aqueous thickeners; porous powders; and additives such as cooling agents, preservatives, fragrances, colorants, pH adjusters, wetting agents, stabilizers, antioxidants, ultraviolet absorbers, chelating agents, adhesives, buffers, solubilizers, solubilizers, and preservatives.

[0032] Formulation and product classification The cell activating agent of the present invention is typically a composition for external use, and in this case, the formulation is not particularly limited as long as it is a formulation that can be applied transdermally, and may be any of liquid, solid, semi-solid (cream, gel, ointment, paste), etc. In addition, the cell activating agent of the present invention may be a non-emulsified formulation such as an aqueous formulation or an oil-based formulation, or may be an emulsion formulation such as an oil-in-water emulsion formulation or a water-in-oil emulsion formulation.

[0033] Furthermore, product categories for the cell activating agent of the present invention include skin external medicines, cosmetics, skin cleansing agents, etc., and preferably skin external medicines and cosmetics.

[0034] More specific examples of the cell activating agent include liquids (including lotions, sprays, aerosols, emulsions, and oils), water-soluble ointments, oily ointments, creams, foams, gels, patches, and other external pharmaceuticals for skin; cosmetics such as ointments, creams, emulsions, skin lotions, cosmetic oils, packs, gels, and other cosmetics; skin cleansers such as body shampoos, hair shampoos, rinses, and other skin cleansers. Cell activating agents in these forms can be prepared by formulating the agent using additives appropriate for the formulation form according to known methods described in the General Provisions for Preparations of the Japanese Pharmacopoeia, 16th Edition, and the like.

[0035] Purpose The cell activating agent of the present invention is used for activating skin cells.

[0036] In particular, the cell activator of the present invention has an excellent activation effect against dryness damage, particularly in cells exposed to dryness. For this reason, the cell activator of the present invention is preferably used for cell activation of skin exposed to an environment that dries the skin (e.g., a dry air environment due to the use of air conditioning or heating, an ultraviolet environment, etc.). Skin in such a state has a significant problem in suppressing or improving the decline in skin function against dryness damage, and the effect of suppressing or improving the decline in skin function is insufficient when only an external preparation having a simple moisturizing effect is applied. However, the cell activator of the present invention exerts an excellent cell activation effect on skin in such a state, and an excellent effect of suppressing or improving the decline is obtained. EXAMPLES

[0037] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these.

[0038] A cell activating agent (liquid, non-emulsion type) was prepared with the composition shown in Table 1, and its cell activating effect was tested. Details of each component are as follows. (A) Fermented birch sap: A liquid obtained by yeast fermentation of sap (undiluted, unconcentrated) from Hokkaido-grown birch using Galactomyces raceii, cultured in a medium containing both yeast extract and peptone. The dry weight of 100 g of the liquid was 0.3 g. The liquid was substantially free of glucose (specifically, the glucose content in the liquid was measured and found to be 0.0% by weight). (B) Betula platyphylla sap: sap (non-diluted, non-concentrated) from Betula platyphylla grown in Hokkaido. The dry weight of 100 g of the sap was 0.8 g. The glucose content of the sap was 0.10% by weight. ·D-PBS: Phosphate buffered saline

[0039] Human dermal fibroblasts (NB1RGB) were seeded on a 24-well plate and cultured until confluent. After washing with D-PBS, 1 ml / well of the cell activator shown in Table 1 was added and the plate was left to stand in a CO2 incubator for 10 minutes. The cell activator was then removed and the plate was dried in a CO2 incubator for 45 minutes. The cell viability was then measured by MTT assay. The cell viability was calculated as a relative value with the cell viability in Comparative Example 1 (control) taken as 100.

[0040] The "cell activation score (actual measurement value)" was calculated from the cell viability based on the following formula. It can be evaluated that the higher the cell activation score (actual measurement value), the higher the cell activation effect.

number

[0041] Furthermore, for Examples 2 to 4, which include a combination of component (A) and component (B), a "cell activation score (predicted value)" was calculated by taking a weighted average of the cell activation scores (actual values) for Example 1, which includes component (A) alone, and Comparative Example 2, which includes component (B) alone. Furthermore, a "cell activation enhancement index" was derived by dividing the cell activation score (actual value) by the cell activation score (predicted value). A cell activation enhancement index of more than 1 can be evaluated as having a synergistic effect, and a larger cell activation enhancement index can be evaluated as a higher level of synergistic effect. The results are shown in Table 1.

[0042] [Table 1]

[0043] As shown in Table 1, the fermented birch sap product was found to have an excellent cell activation effect even against extreme dry damage (Example 1). Furthermore, by combining the fermented birch sap product with birch sap, an even more excellent cell activation effect against the dry damage was found (Examples 2 to 4). In particular, when these components were combined at a specific blend ratio, a significantly more remarkable cell activation effect against the dry damage was found (Example 3).

Claims

1. (A) A skin cell activator containing fermented birch sap.

2. The skin cell activating agent according to claim 1 , further comprising (B) birch sap.

3. 3. The skin cell activating agent according to claim 2, wherein the total amount of glucose contained in the components (A) and (B) is 0.001 to 0.1% by weight.

4. 3. The skin cell activating agent according to claim 2, comprising 0.1 to 20 parts by dry weight of said component (B) per 1 part by dry weight of said component (A).

5. 2. The skin cell activating agent according to claim 1, wherein the content of the component (A) is 0.005 to 1% by weight on a dry basis.

6. The cell activating agent according to claim 1 , which is used on skin exposed to an environment that dries out the skin.

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