Skin cell activator, desmoglein reducer for skin, nerve growth factor production inhibitor, skin irritation reliever, skin barrier function improver, and topical skin composition

Abstract

To provide a formulation capable of exhibiting at least one of skin cell activation action, cutaneous desmoglein reduction action, cutaneous nerve growth factor production inhibition action, skin irritation alleviation action, and skin barrier function improvement action, and to provide a skin external composition comprising the formulation.SOLUTION: Provided are skin external compositions and so on comprising a β-chitin fiber as an active ingredient and preferably further comprising a polyhydric alcohol.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to, for example, a skin cell activator, a skin desmoglein reducing agent, a nerve growth factor production inhibitor, a skin irritation reliever, a skin barrier function improver, and a topical skin composition, which are used by being applied to the skin.

Background Art

[0002] Conventionally, polysaccharides such as cellulose contained in plant cell walls or chitin contained in the shells of crustaceans have been known. As chitin, in addition to α-chitin contained in the shells of crustaceans as described above, β-chitin contained in squid pen etc. is known.

[0003] Since the above-mentioned cellulose and α-chitin have high crystallinity, they do not dissolve in water and have low dispersibility in water. α-chitin is known to have physiological activity functions such as an immunostimulating action and a wound healing action on skin cells. However, since α-chitin has high crystallinity, it is difficult to stably disperse it in topical skin compositions such as skin care cosmetics such as gels, lotions, and emulsifying creams. On the other hand, β-chitin has lower crystallinity than α-chitin because it has fewer hydrogen bonds in the molecule and can swell in water. Therefore, β-chitin has higher degradability by enzymes and biocompatibility than α-chitin (Non-Patent Document 1).

[0004] Regarding these polysaccharides, in recent years, polysaccharide fibers that have been fibrillated to a nano-order thickness to improve dispersibility have been known. The diameter of such polysaccharide fibers is, for example, 1 to 100 nm, and the length thereof is, for example, 100 times or more the diameter. Examples of the fibrillated polysaccharide fibers as described above include cellulose fibers derived from plants (Non-Patent Document 2), α-chitin fibers derived from crustaceans, etc. (Patent Document 1). Although cellulose fibers and α-chitin fibers have improved dispersibility in water compared to before fibrillation, they still do not have good dispersibility due to their high crystallinity. For example, in order for α-chitin to fully exhibit the above-described immunostimulatory effect and wound healing effect, it is considered necessary to disperse α-chitin more stably.

[0005] By the way, in recent years, research on skin functions has been actively conducted. For example, an active ingredient that activates skin cells to enhance the proliferation ability of epidermal cells, an active ingredient that reduces desmoglein that can inhibit the normal turnover function of the stratum corneum, an active ingredient that suppresses the production of nerve growth factor in the skin, an active ingredient that suppresses the production of nerve growth factor that promotes the elongation of sensory nerve fibers that can cause itching, etc. to the epidermis, an active ingredient that relieves skin irritation such as itching caused by surfactants, etc., or an active ingredient that improves the skin barrier function, etc. have been studied.

[0006] However, such active ingredients have not yet been fully studied. Therefore, there is a demand for an active ingredient that can exert the above-described effects on skin functions.

[0007] In view of the above viewpoints and the like, the present invention aims to provide a preparation containing an active ingredient capable of at least one of activation of skin cells, reduction of skin desmoglein, suppression of nerve growth factor production, alleviation of skin irritation, or improvement of skin barrier function, and a topical skin composition containing such an active ingredient.

Prior Art Documents

Patent Documents

[0008]

Patent Document 1

Non-Patent Documents

[0009]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0010] In view of the above problems and the like, the present invention aims to provide a preparation capable of exhibiting at least one of a skin cell activation effect, a skin desmoglein reduction effect, a skin nerve growth factor production inhibitory effect, a skin irritation alleviation effect, and a skin barrier function improvement effect, and a topical skin composition containing the preparation.

Means for Solving the Problems

[0011] The skin cell activator, skin desmoglein reducer, skin nerve growth factor production inhibitor, skin irritation reliever, and skin barrier function improver according to the present invention are each characterized by containing β-chitin fiber as an active ingredient.

[0012] The topical skin composition according to the present invention is characterized by containing β-chitin fiber and a polyhydric alcohol. The topical skin composition according to the present invention preferably further contains at least one of water and a polar liquid oil. The topical skin composition according to the present invention preferably further contains at least one of cellulose fiber and an amphiphilic chitosan derivative. In the topical skin composition according to the present invention, the amphiphilic chitosan derivative is preferably partially myristoylated carboxymethyl chitosan or partially myristoylated chitosan salt.

[0013] The topical skin composition according to the present invention is preferably for improving epidermal keratinization, preventing and improving rough skin or preventing and improving acne, or for application to dry skin with redness or itching.

Effects of the Invention

[0014] According to each of the above-mentioned preparations of the present invention and the topical skin composition, at least one of a skin cell activation effect, a skin desmoglein reduction effect, a skin nerve growth factor production inhibitory effect, a skin irritation alleviation effect, and a skin barrier function improvement effect can be exhibited.

Mode for Carrying Out the Invention

[0015] An embodiment of the preparation according to the present invention and a topical skin composition containing these preparations will be described. The preparation of this embodiment is a skin cell activator, a skin desmoglein reducing agent, a skin nerve growth factor production inhibitor, a skin irritation alleviating agent, or a skin barrier function improving agent. Hereinafter, each of the preparations and the topical skin composition may be simply referred to as a composition.

[0016] The composition of this embodiment contains at least β-chitin fibers.

[0017] The β-chitin fibers contained in the composition of this embodiment include fibrous substances formed of β-chitin. Since such fibrous substances are usually water-insoluble, they can be dispersed in a solvent containing water. The β-chitin fibers are formed of a plurality of fibrous substances, and in each fibrous substance, a plurality of sugar chains bundled together extend in the fiber length direction of the fibrous substance. The thickness of each fibrous substance is usually 1 nm or more and 100 nm or less. The aspect ratio of each fibrous substance may be, for example, 50 or more and 10,000 or less.

[0018] The β-chitin fibers are formed of a plurality of fibrous substances, and in each fibrous substance, a plurality of sugar chains of poly-β-1,4-N-acetyl-D-glucosamine extend in the fiber length direction of the fibrous substance while being adjacent to each other in the fiber diameter direction. In the fibrous substance of the β-chitin fiber, the orientations of the β-1,4 bonds of the adjacent sugar chains are the same as each other in the sugar chain length direction. On the other hand, in the fibrous substance of the α-chitin fiber mentioned for reference, the orientations of the β-1,4 bonds of the sugar chains of adjacent poly-β-1,4-N-acetyl-D-glucosamine are opposite to each other in the sugar chain length direction.

[0019] By containing the above-mentioned β-chitin fibers, the composition of the present embodiment can exhibit at least one of the following effects: skin cell activation effect, skin desmoglein reduction effect, skin nerve growth factor production inhibition effect, skin irritation alleviation effect, or skin barrier function improvement effect, as is clear from the experimental results shown in detail later.

[0020] (Skin cell activation effect) When the proliferation ability of epidermal cells decreases with aging or due to ultraviolet rays or the like, the stratum corneum turnover function also decreases. As a result, skin dryness and roughness may occur, and epidermal wrinkles and rough skin may develop. On the other hand, epidermal growth factor (hereinafter also referred to as EGF) in the skin can improve the decrease in the proliferation function of epidermal cells, but it is known to decrease with aging (A Tanaka et al, J Vet. Sci. 67, 9, p909-913

[2005] ). The skin cell activator of the present embodiment can exhibit a skin cell activation effect and promote the proliferation of epidermal cells in the same manner as EGF.

[0021] (Skin desmoglein reduction effect) Desmoglein is a cell adhesion molecule protein that plays an important role in cell adhesion of stratum corneum cells and epidermal keratinocytes. When a large amount of desmoglein remains in the stratum corneum epidermis, the normal turnover of the aging stratum corneum, which is sequentially peeled off, is inhibited, and stratification of stratum corneum cells may be caused. On the other hand, a desmoglein reducing agent that reduces desmoglein is known (Japanese Patent Laid-Open No. 2016-37501). By this preparation, desmoglein in stratum corneum cells can be reduced, the disturbance of turnover can be suppressed, and skin dullness can be improved. The skin desmoglein reducing agent of the present embodiment can similarly exhibit a desmoglein reduction effect in stratum corneum cells.

[0022] (Skin nerve growth factor production inhibition effect) Nerve growth factor (NGF) in the skin is released from epidermal cells due to dryness, external stimuli, etc. The released NGF promotes the extension of sensory nerve fibers into the epidermis. The sensory nerve fibers that have extended into the epidermis can cause itching and the like. Therefore, NGF is considered to be one of the causes of symptoms of itching due to dryness, skin diseases accompanied by itching (such as atopic dermatitis), etc. (Kenji Takamori, Journal of the Japan Society for Cosmetic Sciences, VOL29, No.2, p130-133

[2005] ). As an active ingredient that suppresses the production of this NGF, an extract derived from oyster leaf is known (Japanese Patent Laid-Open No. 2014-159383). Similarly, the skin nerve growth factor production inhibitor of this embodiment can suppress the production of NGF.

[0023] (Skin irritation-relieving effect) Rough skin and sensitive skin often develop dryness, erythema, itching, or flushing due to skin irritation caused by surfactants and the like. Therefore, in order to prevent these conditions, there is a demand for a preparation that relieves skin irritation caused by irritating components such as surfactants. The skin irritation-relieving agent of this embodiment can exhibit an effect of relieving skin irritation.

[0024] (Skin barrier function-improving effect) In rough skin and sensitive skin, the skin barrier function often deteriorates due to surfactants, alcohol, etc., worsening symptoms such as dryness, erythema, and itching. Therefore, in order to prevent these conditions, there is a demand for a preparation that improves the skin barrier function caused by surfactants, alcohol, etc. The skin barrier function-improving agent of this embodiment can improve the deteriorated skin barrier function.

[0025] Since the skin external composition of this embodiment containing β-chitin fiber has each of the above-described effects, it can improve epidermal keratinization. Thereby, epidermal skin troubles such as skin dryness, erythema, itching, acne, loss of firmness and softness, scales, wrinkles, and dark circles can be prevented or improved.

[0026] The above-mentioned β-chitin fiber can be obtained, for example, from the cartilage of squid. The β-chitin fiber can be obtained, for example, by subjecting β-chitin obtained from the cartilage of squid to fibrillation treatment (wet fibrillation treatment) in water. As the fibrillation treatment method, a high-pressure homogenizer method, a microfluidizer method, a ball mill pulverization method, etc. are adopted.

[0027] The above-mentioned β-chitin fiber may be in the state of a solid (for example, powder) before being blended into the composition, or may be in a state of being dispersed in water (a state contained in an aqueous dispersion). The β-chitin fiber may be blended into the composition, for example, in a state contained in an aqueous dispersion. As the aqueous dispersion containing the above-mentioned β-chitin fiber, for example, a product named "β-chitin nanofiber dispersion" (manufactured by Yaegaki Fermentation Technology Research Co., Ltd.) can be used.

[0028] In order to more effectively exert the physiological activity function of the β-chitin fiber, each of the above-mentioned preparations in this embodiment preferably contains 0.001% by mass or more and 5.000% by mass or less (in terms of solid content) of the β-chitin fiber. Further, the skin external composition in this embodiment preferably contains 0.001% by mass or more (more preferably 0.010% by mass or more) and 1.000% by mass or less (in terms of solid content) of the β-chitin fiber. By having the above-mentioned content, there is an advantage that various actions described above can be more effectively exerted.

[0029] The composition of this embodiment (particularly the skin external composition) preferably contains a polyhydric alcohol in addition to the above-mentioned β-chitin fiber. When the skin external composition contains a polyhydric alcohol, aggregation of the β-chitin fiber over time can be suppressed. The β-chitin fiber has dispersibility in water and also has good degradability by biological enzymes such as lysozyme in a living body, but it may aggregate over time in a solvent containing water (for example, in the composition of this embodiment). On the other hand, when the composition contains a polyhydric alcohol, aggregation of the β-chitin fiber over time can be suppressed. In addition, when a skin external composition containing β-chitin fibers is applied to the skin, the β-chitin fibers may aggregate on the skin. If such aggregation occurs, the compatibility with the skin after application is not necessarily good. On the other hand, when the composition contains a polyhydric alcohol, the β-chitin fibers can be stably formulated in the composition, resulting in a skin external composition that is good in terms of skin compatibility and permeability.

[0030] A polyhydric alcohol is a compound having a plurality of hydroxy groups (hydroxyl groups) in the molecule. Examples of polyhydric alcohols include dihydric alcohols having two hydroxy groups in the molecule, trihydric alcohols having three hydroxy groups in the molecule, and tetrahydric alcohols having four hydroxy groups in the molecule.

[0031] Examples of dihydric alcohols include ethylene glycol, propylene glycol, 1,3-propanediol (trimethylene glycol), butylene glycol (1,2-butylene glycol, 1,3-butylene glycol, 2,3-butylene glycol), 1,4-butanediol (tetramethylene glycol), 3-methyl-1,3-butanediol, 2-butene-1,4-diol, 1,5-pentanediol (pentamethylene glycol), 1,2-pentanediol (pentylene glycol), isoprene glycol (isopentyl diol), hexylene glycol, diethylene glycol, triethylene glycol, hexaethylene glycol, dodecaethylene glycol, dipropylene glycol, glycerin mono 2-ethylhexyl ether, polyethylene glycol (polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 20000, polyethylene glycol 35000, etc.), polypropylene glycol (polypropylene glycol 700, polypropylene glycol 1000, polypropylene glycol 2000, etc.). Examples of the trivalent alcohol include glycerin and trimethylolpropane. Examples of the tetravalent alcohol include diglycerin. In addition, polyglycerin, sorbitol, etc. may be mentioned.

[0032] The skin-external composition of this embodiment preferably contains a divalent polyhydric alcohol such as dipropylene glycol or 1,3-butylene glycol, or a trivalent polyhydric alcohol such as glycerin. Thereby, the aggregation of β-chitin fibers over time can be more suppressed.

[0033] In the skin-external composition of this embodiment, the concentration of the polyhydric alcohol is preferably 0.1% by mass or more and 50.0% by mass or less, and more preferably 1.0% by mass or more and 20.0% by mass or less. By having the above content, the aggregation of β-chitin fibers over time can be more suppressed.

[0034] The skin-external composition of this embodiment preferably further contains at least one of water and polar liquid oil. When the skin-external composition contains a polar liquid oil, the aggregation of β-chitin fibers over time can be suppressed, and the permeability and affinity of the β-chitin fibers to the skin can be further enhanced. Therefore, there is an advantage that the stratum corneum turnover function can be further improved.

[0035] The above-mentioned polar liquid oil is an oil having an ester bond in the molecule and having fluidity at 25°C.

[0036] The polar liquid oil is not particularly limited as long as it is generally blended in cosmetics and the like. Examples of the polar liquid oil include liquid monoester oil, liquid diester oil, liquid triester oil (including liquid triglyceride oil), liquid tetraester oil, etc.

[0037] Examples of the liquid monoester oils include isopropyl myristate, cetyl octanoate (cetyl 2-ethylhexanoate), octyldodecyl myristate, isopropyl palmitate, 2-ethylhexyl paramethoxycinnamate, isononyl isononanoate, isotridecyl isononanoate, 2-hexyldecyl isostearate, isostearyl myristate, and the like. Examples of the liquid diester oils include neopentyl glycol di(2-ethylhexanoate), neopentyl glycol dicaprylate, distearyl malate, cetyl 2-ethylhexanoate, neopentyl glycol di(2-ethylhexanoate), glyceryl distearate, and the like. Examples of the liquid triester oils include natural oils and fats and synthetic oils and fats. Examples of the natural oils and fats include avocado oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, jojoba oil, and the like. Examples of the synthetic oils and fats include glyceryl tri(2-ethylhexanoate), trimethylolpropane triisostearate, glyceryl tri(caprylic / capric acid), and the like. Examples of the liquid tetraester oils include pentaerythrityl tetra(2-ethylhexanoate), and the like.

[0038] The composition of this embodiment preferably contains 0.01% by mass or more and 50.0% by mass or less of the above polar liquid oil, and more preferably contains 1.0% by mass or more and 20.0% by mass or less. Thereby, the aggregation of β-chitin fibers over time in the composition can be further suppressed.

[0039] As the above polar liquid oil, commercially available products can be used. Note that, as the polar liquid oil, one type may be used alone, or two or more types may be used in combination.

[0040] Note that the composition of this embodiment may contain non-polar liquid oils such as liquid hydrocarbon oils and liquid silicone oils. Examples of the liquid hydrocarbon oil as the nonpolar liquid oil include liquid paraffin, heavy liquid isoparaffin, squalane, squalene, and the like. Examples of the liquid silicone oil as the nonpolar liquid oil include methylpolysiloxane, methylhydrogenpolysiloxane, methylphenylpolysiloxane, polyether-modified organopolysiloxane, fluorine-modified organopolysiloxane, amino-modified organopolysiloxane, and the like.

[0041] The composition of the present embodiment preferably contains the above polar liquid oil and a surfactant. By including a surfactant in the composition, aggregation of β-chitin fibers can be suppressed, and the polar liquid oil can be dispersed well.

[0042] Examples of the above surfactant include nonionic surfactants such as fatty acid monoglyceride, polyoxyethylene fatty acid ester, polyoxyethylene alkyl ether, polyglycerin fatty acid ester; cationic surfactants such as benzalkonium chloride; amphoteric surfactants; anionic surfactants, and the like.

[0043] The skin external composition of the present embodiment preferably further contains at least one of cellulose fiber and an amphiphilic chitosan derivative.

[0044] Cellulose fiber can be obtained, for example, from wood pulp. The cellulose fiber contains a large number of fibrous substances having a thickness of 1 nm or more and 100 nm or less (the aspect ratio is, for example, 50 or more and 10,000 or less). The cellulose fiber can be obtained, for example, by subjecting wood pulp to a defibrillation treatment in water. As the defibrillation treatment method, a high-pressure homogenizer method, a microfluidizer method, a ball mill pulverization method, and the like are adopted.

[0045] By including the above cellulose fibers in the skin external composition of the present embodiment, aggregation of β-chitin fibers can be suppressed. Further, by including the above polar liquid oil and cellulose fibers in the skin external composition, the polar liquid oil can be incorporated into the composition with good dispersibility over time. Even if the skin external composition containing the above polar liquid oil and cellulose fibers does not contain a surfactant, aggregation of β-chitin fibers over time is suppressed by the cellulose fibers, and the dispersibility of the polar liquid oil can be made better. In addition, the compatibility with the skin when the skin external composition is applied to the skin can be made better.

[0046] In the cellulose fibers, a part of the cellulose may be chemically modified. Specifically, it may be hydrophilized at the hydroxyl group portion bonded to the carbon of the glucose unit. More specifically, a part of the above hydroxyl group portion may be carboxymethylated.

[0047] As the cellulose fibers, commercially available products can be adopted. Such products include, for example, the product name "Reocrista C-2SP" (manufactured by Daiichi Kogyo Co., Ltd.), the product name "Serenpia" series (manufactured by Nippon Paper Industries Co., Ltd.), and the like.

[0048] The skin external composition of the present embodiment preferably contains the above cellulose fibers in an amount of 0.001% by mass or more and 1.000% by mass or less, more preferably 0.01% by mass or more and 0.50% by mass or less, in terms of solid content.

[0049] The amphiphilic chitosan derivative that can be incorporated into the skin external composition of the present embodiment is a chitosan derivative (including the salt state) in which at least a part of the amino groups bonded to the carbon at the 2-position in a plurality of D-glucosamine structures constituting chitosan is acylated. Further, in the above amphiphilic chitosan derivative, at least a part of the hydroxyl groups adjacent to the carbon at the 6-position in a plurality of D-glucosamine structures may be hydrophilized. Note that the above amphiphilic chitosan derivative may be in a salt state and can be dissolved in water.

[0050] Examples of the amphiphilic chitosan derivative include, for example, an acylated chitosan derivative in which a monovalent organic acid is amide-bonded to the amino group. In other words, examples of the amphiphilic chitosan derivative include, for example, an acylated chitosan derivative in which one H of the amino group is substituted with an acyl group. As the amphiphilic chitosan derivative, a partially acylated chitosan derivative in which a part of the amino groups are acylated is preferable. In the amphiphilic chitosan derivative, the H of the hydroxy group bonded to the carbon (for example, the carbon at the 3-position) constituting the pyranose ring may be substituted with an acyl group.

[0051] Examples of the organic acid that forms an amide bond as described above include fatty acids having 12 to 22 carbon atoms. Specifically, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, etc. are included. In other words, examples of the acyl group as the substituent as described above include aliphatic acyl groups having 12 to 22 carbon atoms. Specifically, examples of the aliphatic acyl group include lauroyl group, myristoyl group, palmitoyl group, stearoyl group, behenoyl group, etc. In other words, examples of the amphiphilic chitosan derivative include partially aliphatic acylated chitosan derivatives such as partially lauroylated chitosan derivative, partially myristoylated chitosan derivative, partially palmitoylated chitosan derivative, partially stearoylated chitosan derivative, and partially behenoylated chitosan derivative (all including the salt state). Among them, a partially myristoylated chitosan derivative is preferable.

[0052] In the amphiphilic chitosan derivative, examples of the functional group (hydrophilic functional group) bonded to the oxygen atom adjacent to the carbon at the 6-position include carboxymethyl group, hydroxyethyl group, hydroxypropyl group, etc., and a carboxymethyl group is preferable.

[0053] The amphiphilic chitosan derivative (including the salt state) further chemically modified at the oxygen atom portion adjacent to the 6-position carbon as described above is preferably a partially aliphatic acylated carboxymethyl chitosan derivative, more preferably at least one selected from the group consisting of a partially lauroylated carboxymethyl chitosan derivative, a partially myristoylated carboxymethyl chitosan derivative, a partially palmitoylated carboxymethyl chitosan derivative, a partially stearoylated carboxymethyl chitosan derivative, and a partially behenoylated carboxymethyl chitosan derivative, and even more preferably a partially myristoylated carboxymethyl chitosan derivative.

[0054] Examples of the salt state of the above amphiphilic chitosan derivative include organic acid salts such as formate, acetate, butyrate, lactate, citrate, and pyrrolidone carboxylate, or hydrochloride, sulfate, etc. Alternatively, the above amphiphilic chitosan derivative may be in the state of a Na salt or a K salt.

[0055] In the above amphiphilic chitosan derivative, the amino group of chitosan is partially aliphatically acylated, and if necessary, the hydroxyl group portion bonded to the 6-position carbon of chitosan is hydrophilized, so that it has an affinity not only for water but also for oil components, and thus has so-called amphiphilicity. Since the composition of this embodiment contains an amphiphilic chitosan derivative, the aggregation of β-chitin fibers over time can be suppressed, and the formulation stability can be enhanced. Also, the dispersibility in polar liquid oils can be made better. Further, the affinity for the skin when the topical skin composition is applied to the skin can be made better.

[0056] The preferred above amphiphilic chitosan derivative is a partially aliphatic acylated chitosan salt in which a fatty acid group having 8 to 20 carbon atoms is bonded to a part of the amino group bonded to the 2-position carbon or the hydroxyl group bonded to the 3-position carbon in chitosan. The introduction rate of the aliphatic group may be, for example, 0.1% or more and 50.0% or less in terms of molar conversion, or 10.0% or more and 20.0% or less. As such amphiphilic chitosan derivatives, commercially available products can be adopted. Examples of such products include partially myristoylated chitosan pyrrolidone carboxylate (product name: "PM-chitosan", manufactured by Piass Co., Ltd., introduction rate of aliphatic group: 17.0%), partially stearoylated chitosan lactate, partially myristoylated chitosan glycolate, and the like.

[0057] A more preferable amphiphilic chitosan derivative is (partially) aliphatic acylated carboxymethyl chitosan in which a fatty acid group having 8 to 20 carbon atoms is bonded to a part of the amino group bonded to the carbon at the 2-position in carboxymethyl chitosan. The introduction rate of the aliphatic group may be, for example, 0.1% or more and 50.0% or less in terms of molar conversion, or may be 10.0% or more and 20.0% or less. Examples of such aliphatic acylated carboxymethyl chitosan include partially myristoylated carboxymethyl chitosan (product name: "MC-chitosan", manufactured by Piass Co., Ltd., introduction rate of aliphatic group: 12.0%), partially stearoylated carboxymethyl chitosan, and the like.

[0058] The introduction rate (%) of the aliphatic group in the partially aliphatic acylated carboxymethyl chitosan indicates the introduction rate per 100 residues of hexosamine which is a constituent monosaccharide of carboxymethyl chitosan. For example, the partially aliphatic acylated carboxymethyl chitosan having an introduction rate of 10.0% of the aliphatic group means that 10 myristoyl groups are introduced into 100 residues of carboxymethyl glucosamine which is a constituent monosaccharide. As the partially myristoylated carboxymethyl chitosan, those in which the myristoyl group is introduced into carboxymethyl chitosan having an average molecular weight of 500,000 to 1,000,000 at an introduction rate of 0.1% or more and 50.0% or less are preferable, and those introduced at an introduction rate of 10.0% or more and 20.0% or less are more preferable.

[0059] The composition of this embodiment preferably contains 0.001% by mass or more and 0.50% by mass or less (in terms of solid content) of the above amphiphilic chitosan derivative, and more preferably 0.01% by mass or more and 0.1% by mass or less (in terms of solid content). Thereby, the aggregation of β-chitin fibers over time in the composition can be further suppressed, and the formulation stability can be further enhanced. In addition, the affinity and penetration feeling to the skin when the composition is applied to the skin can also be enhanced.

[0060] In the composition of this embodiment, the mass ratio (A / B) of the above β-chitin fiber (A) to the above polyhydric alcohol (B) is preferably 0.001 or more and 0.500 or less, more preferably 0.010 or more and 0.100 or less, and even more preferably 0.005 or more and 0.050 or less in terms of solid content of the β-chitin fiber. Thereby, the aggregation of β-chitin fibers over time can be further suppressed.

[0061] In the composition of this embodiment, the mass ratio (A / C) of the above β-chitin fiber (A) to the above polar liquid oil (C) is preferably 0.001 or more and 0.500 or less, more preferably 0.005 or more and 0.200 or less, and even more preferably 0.010 or more and 0.100 or less in terms of solid content of the β-chitin fiber. Thereby, the aggregation of β-chitin fibers over time can be further suppressed, and the affinity and penetration feeling to the skin can be further enhanced.

[0062] In the composition of this embodiment, the mass ratio (A / D) of the above β-chitin fiber (A) to the above amphiphilic chitosan derivative (D) is preferably 1 or more and 20 or less, and more preferably 2 or more and 15 or less in terms of solid content of the β-chitin fiber. Thereby, the aggregation of β-chitin fibers over time can be further suppressed, and the formulation stability can be further enhanced.

[0063] The above composition may further contain a thickener, a preservative, etc. in addition to the above components. Examples of the thickener (water-soluble polymer) include quince seed, casein, dextrin, gelatin, pectin, starch, carrageenan, alginic acid or its salts, hyaluronic acid or its salts, chondroitin sulfate or its salts, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate salts, carboxyvinyl polymer, or polyethyleneimine, etc.

[0064] The properties and appearance of the composition of the present embodiment are not particularly limited. The composition of the present embodiment may be, for example, liquid, semi-solid (gel-like, cream-like, etc.), or solid (powder-like, tablet, or sheet-like, etc.). The composition of the present embodiment may be included in the content of an aerosol product.

[0065] The composition (topical composition for skin) of the present embodiment can be produced by mixing and stirring each component to be blended. As the apparatus for stirring, general ones can be used. If necessary, it may be stirred while heating.

[0066] The composition (topical composition for skin) of the present embodiment may be used for the purpose of improving epidermal keratinization, may be used for the purpose of preventing and improving rough skin or preventing and improving acne, or may be used for the purpose of applying to dry skin with redness or itching.

[0067] The composition (topical composition for skin) of the present embodiment is usually applied to the skin for use. The above composition is applied and used, for example, to the skin of the face, neck, limbs, scalp, hair, and also to the mucous membranes in the nostrils, lips, ears, genitals, anus, etc. Further, it may be blended in a bath agent for use or may be blended in a skin patch for use. The above composition is not particularly restricted by the classifications such as cosmetics, quasi-drugs, pharmaceuticals, etc. under the Pharmaceutical Affairs Law and is applicable to several fields.

[0068] Each preparation and topical skin composition of the present invention is as exemplified above, but the present invention is not limited to the exemplified embodiments. Further, in the present invention, various forms employed in general cosmetics, topical skin preparations, etc. can be employed as long as the effects of the present invention are not impaired.

Examples

[0069] Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

[0070] The performance evaluation of each preparation (composition) was carried out as follows.

[0071] [Experiment 1] (Evaluation related to epidermal cell activation (promotion of epidermal cell proliferation)) The epidermal cell proliferation effect of β-chitin fibers was evaluated using epidermal keratinocytes (NHEK). A 1.60% by mass β-chitin fiber aqueous dispersion was used. NHEK was seeded in a 24-well plate at a density of 1×10 4 cells / well. After 24 hours, β-chitin fibers were mixed and a medium from which human EGF (hEGF) had been removed was added. hEGF was selected as the cell growth factor for the positive control. After culturing for 48 hours, the cell viability was measured using a cell counting kit-8 (manufactured by Dojindo Laboratories). As a result (see Table 1), when the 1.6% by mass β-chitin fiber solution was adjusted to 0.1% by mass and 1.0% by mass, the NHEK cell viability increased, and a skin cell proliferation effect equal to or higher than that of the positive control was confirmed.

[0072]

Table 1

[0073] [Experiment 2] (Evaluation related to suppression of nerve growth factor (NGF) production) The NGF production inhibitory effect of β-chitin fibers was evaluated using epidermal keratinocytes (NHEK). 1. A 1.60 mass% β-chitin fiber aqueous dispersion was used. NHEK was seeded in a 6-well plate at 20×10 4 cells / well and cultured for 48 hours. After 24 hours of culture, 100 nM of substance P (SP), a neuropeptide that enhances NGF production, was added. Then, a medium containing β-chitin fibers was added and cultured for 24 hours. The amount of NGF produced was determined from the collected medium using an ELISA kit (NGF ELISA Kit, manufactured by Funakoshi). As can be seen from Table 2, NGF production was observed by adding SP (SP treatment). On the other hand, NGF production could be suppressed by adding β-chitin fibers.

[0074] [Table 2]

[0075] [Experiment 3] (Evaluation related to reduction of desmoglein in the skin) Using epidermal keratinocytes (NHEK), the effect of β-chitin fibers on reducing desmoglein was verified. In addition, it was verified by microarray analysis that comprehensively evaluates each gene expression. NHEK was seeded in a 6-well plate at 15×10 4 cells / well and cultured for 48 hours. The medium was replaced with a medium containing β-chitin fibers and cultured for 24 hours. After culture, RNA was extracted and purified using a PureLink RNA mini kit (Thermo Fisher) and stored at -80°C. After thawing, the RNA concentration was measured and confirmed. Then, samples were collected and microarray analysis (array type: Human Gene2.O ST Array) by Agilent Technologies was performed. Referring to the analysis results, genes with sufficient expression signal intensity (5 or more) and an expression ratio to the control of 1.5 times or more or 0.66 times or less were determined to have fluctuating expression. As a result (see Table 3), it was found that the addition of β-chitin fibers particularly reduced the gene expression of desmoglein 1 (DSG1) by nearly half among many gene species.

[0076] [Table 3]

[0077] [Experiment 4] (Evaluation related to skin irritation relief) An evaluation test of the skin irritation inhibitory effect of β-chitin fiber was carried out using a human skin model (TESTSKIN LSE-high, manufactured by Toyobo Co., Ltd.). An aqueous solution of 0.5% by mass sodium dodecyl sulfate (SDS), which is a stimulant component, was added to the surface of the human skin model, and the cell viability was measured using a cell counting kit-8 (manufactured by Dojindo Laboratories) after 48 hours of culture. As shown in Table 4, by pretreating with a solution containing 5.0% by mass of 1.6% by mass β-chitin fiber solution, the cytotoxicity caused by 0.5% by mass SDS, which is a stimulant component, was significantly suppressed, and it was confirmed that it has an excellent skin irritation relief effect. When observing the tissue section image of SDS-treated skin, tissue damage to the epidermal basement membrane due to SDS stimulation was confirmed, but no tissue damage due to SDS stimulation was observed with the addition of β-chitin fiber.

[0078] [Table 4]

[0079] Next, the preparations of the following Example Formulations 1 and 2 and Comparative Formulation were prepared, [Experiment 5] (Improvement effect on skin barrier function and skin erythema) [Experiment 6] (Evaluation of human usefulness for rough skin, dry itching, and acne redness) were each carried out for the evaluation test.

[0080] [Example Formulation 1] β-Chitin Fiber-containing Lotion [% by mass] (1) Pentaerythrityl tetraethylhexanoate 3.0 (2) Isopropyl myristate 1.0 (3) Glycerin 8.0 (4) Butylene glycol 2.0 (5) Cellulose fiber dispersion 3.0 (Manufactured by Daiichi Sankyo Co., Ltd., product name: Reocrista 2SP) (6) Purified water Remaining amount (7) 1.6 mass% β-chitin fiber dispersion 5.0

[0081] [Example of Practical Prescription 2] β-chitin fiber-containing lotion The formulation composition is the same as that of Prescription Example 1, except that 1.0 mass% of the 1.6 mass% β-chitin fiber dispersion of (7) is blended.

[0082] [Comparative Prescription Example] Placebo lotion As a control preparation for comparison, a comparative prescription example without the β-chitin fiber of (7) was prepared.

[0083] [Method for Preparing the Formulations of the Above Prescription Examples] The oil phases of (1) to (2) heated to 60°C were added to the heated aqueous phases of (3) to (6), and stirred with a homomixer. Finally, a 1.6 mass% dispersion of β-chitin fiber as the active ingredient (blended with 5.0 mass% or 1.0 mass% respectively) was added. Stirring was continued to prepare a cloudy lotion. The formulations of Prescription Examples 1 and 2 had good familiarity and penetration feeling after being applied to the skin, and no aggregation on the skin was observed when applied to the skin. In the stability test, no separation or precipitation of β-chitin fiber was observed after standing at room temperature for 1 month, 45°C for 1 month, and 50°C for 1 month, so it was confirmed that the formulation stability was high.

[0084] [Experiment 5] [Improving Action on Skin Barrier Function and Skin Erythema] The outer side of the forearm of 5 healthy men and women was used as the observation site. Cumulative treatment with a 10 mass% sodium dodecyl sulfate (SDS) solution was performed on the skin to destroy the skin barrier function by SDS stimulation. As a result, a rough skin symptom with erythema having inflammation was artificially induced. After causing rough skin symptoms, the β-chitin fiber-containing lotions of Formulation Examples 1 and 2 and the placebo lotion of the Comparative Formulation Example as a comparative control were continuously applied for 2 weeks. Then, at the first and second weeks, the TEWL and erythema level were measured respectively. The trans-epidermal water loss (TEWL), which is an index of the skin barrier function, was measured using a Tewameter TM (manufactured by Integra). The higher the skin barrier function, the lower the TEWL. Also, the erythema level of the skin was measured using a Mexameter MX18 (manufactured by Integra). After washing the measurement site with hot water, the subject was kept at rest for 30 minutes at a room temperature of 25°C and a humidity of 50%, and then the measurement was carried out. Regarding the improvement effect of the skin barrier function and the erythema level of the skin, the change rate (%) of the measured value after the application compared to before the application was adopted as an index.

[0085] The results of Experimental Example 5 are shown in Table 5. By the cumulative treatment with a 10% by mass sodium dodecyl sulfate (SDS) solution three times, the trans-epidermal water loss (TEWL) increased and the skin barrier function decreased. Also, the skin became red and the erythema level increased. The β-chitin fiber-containing lotions of Formulation Examples 1 and 2 had a greater reduction rate in the trans-epidermal water loss (TEWL) and the erythema level of the skin after the application compared to the placebo lotion of the Comparative Formulation Example. From this, it can be said that the β-chitin fiber-containing lotions of Formulation Examples 1 and 2 are superior to the placebo lotion of the Comparative Formulation Example in terms of the improvement effect of the skin barrier function and the improvement effect of the skin erythema.

[0086]

Table 5

[0087] [Experiment 6] (Human utility evaluation for skin dryness, skin roughness, skin firmness, acne redness, dry itching) Twelve women aged 30 to 59 years, who were concerned about skin roughness symptoms such as dryness and coarseness of the skin, acne redness, and dry itching, and who could not feel the effect with conventional skin care, and in whom lamellar separation, an indicator of parakeratosis, was observed from stratum corneum observation, were recruited as subjects. The preparation used for the evaluation was the lotion of Formulation Example 1. The subjects were asked to apply the lotion of Formulation Example 1 to their faces (mainly cheeks) twice a day, morning and evening, for 4 weeks, and evaluations by questionnaire were conducted at the 2nd and 4th weeks. As evaluation items by questionnaire, dryness of the skin, coarseness of the skin, firmness of the skin, acne redness, and dry itching were set, and the improvement effect for each evaluation item was evaluated by the VAS method. As a result, from the VAS evaluations after 2 weeks and 4 weeks, the symptoms decreased over time in all items of skin dryness, coarseness, firmness, acne redness, and dry itching. Therefore, excellent improvement effects were confirmed for each symptom.

[0088]

Table 6

[0089] [Experiment 7] (Evaluation of Human Efficacy against Epidermal Parakeratosis) Instead of the lotion of Formulation Example 1, the lotion of Formulation Example 2 was used in the same way, and the stratum corneum evaluation on the forearm was further performed by the same subjects as in [Experiment 6]. Specifically, the stratum corneum before and after use was collected by tape stripping, and a stratum corneum specimen was obtained by BG staining. The stratum corneum specimen was analyzed by corneosimetry to determine the degree of lamellar separation, which is an indicator of epidermal parakeratosis. The degree of lamellar separation before use was 22.9%, but after 2 weeks and 4 weeks, the degrees of lamellar separation were 11.7% and 12.0% respectively, and the improvement was also remarkable in the visual observation of the magnified image of the stratum corneum specimen. These improvement effects were not observed on the forearm as a comparative control without using the lotion of Formulation Example 2.

[0090] Furthermore, for the compositions of each example and each reference example prepared as follows, the skin affinity after application, the aggregability of β-chitin fibers, and the formulation stability were evaluated.

[0091]

Table 7

[0092] <Evaluation of skin affinity> 0.5 g of the formulation was placed on the back of the hand and evaluated from the state where it was made to fit with the finger. ◎: Immediately adheres to the skin, 〇: Takes time to adhere, ×: Aggregates appear and it is difficult to adhere. <Aggregation of β-chitin fibers> Each formulation was sampled on a slide glass, and the presence or absence of aggregability was observed from the microscopic image. ◎: No aggregation is seen, 〇: Slight aggregation is seen, ×: Aggregation is seen. <Stability> A 50 g transparent sample tube was filled with 40 g of the formulation, and the stability after 1 month at 25 °C and 1 month at 45 °C was evaluated. ◎: No separation or precipitation is seen, 〇: Slight separation or precipitation is seen, ×: Separation or precipitation is seen.

[0093] The results of each evaluation are shown in Table 1. In Reference Examples 1 to 6, there were problems in usability (such as skin affinity), and aggregation of β-chitin fibers was sometimes seen, and they were not good in terms of formulation stability. On the other hand, Examples 1 to 5 were excellent in usability (skin affinity). Also, aggregation of β-chitin fibers did not occur, and it was confirmed that, for example, the formulation stability was high as a cosmetic formulation.

[0094] As described above, the preparation and the topical skin composition of the present embodiment can exhibit at least one of the effects of activating skin cells, reducing skin desmoglein, suppressing the production of skin nerve growth factor, alleviating skin irritation, and improving skin barrier function. Thereby, epidermal keratinization can be improved, and epidermal skin troubles such as skin dryness, erythema, itching, acne, reduced firmness and flexibility, scales, wrinkles, and dark circles can be prevented or improved.

Industrial Applicability

[0095] The preparation and the topical skin composition of the present invention are applied to the skin and used, for example, to improve epidermal keratinization to be closer to normal, to prevent or improve rough skin, to prevent or improve acne, and to prevent and reduce dry skin. The preparation and the topical skin composition of the present invention are preferably used, for example, by being directly applied to the stratum corneum. Specifically, it may be used by being applied to dry skin that has developed redness or itching.

Claims

1. A topical composition for skin, comprising β-chitin fibers, a polyhydric alcohol, and at least one of cellulose fibers and an amphiphilic chitosan derivative.

2. The topical composition for skin according to claim 1, further comprising at least one of water and a polar liquid oil.

3. The topical composition for skin according to claim 1 or 2, wherein the amphiphilic chitosan derivative is partially myristoylated carboxymethyl chitosan or partially myristoylated chitosan.

4. The topical composition for skin according to any one of claims 1 to 3, which is for improving epidermal keratinization.

5. The topical composition for skin according to any one of claims 1 to 3, which is for preventing and improving rough skin or preventing and improving acne.

6. The topical composition for skin according to any one of claims 1 to 3, which is for application to dry skin with redness or itching.

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