Horny layer exfoliation improver

Abstract

To provide a technique that improves the skin's function for horny layer exfoliation, thereby enhancing skin texture.SOLUTION: A horny layer exfoliation improver contains carbon dioxide and Melia toosendan Sieb. et Zucc. extract as active ingredients.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for improving stratum corneum desquamation, which normalizes stratum corneum desquamation. [Background technology]

[0002] The skin has the functions of preventing invasion of foreign substances and microorganisms from the outside world and maintaining homeostasis. The stratum corneum, the outermost layer of the epidermis, is mainly composed of intercellular lipids, natural moisturizing factors (NMFs), and proteins.

[0003] The adhesive structure between keratinocytes (corneodesmosomes) is important for the formation of the stratum corneum. Corneodesmosomes are composed of multiple proteins, including desmoglein 1 (DSG1) and desmocollin 1 (DSC1). Corneodesmosomes are cleaved by proteases such as kallikrein 5 (KLK5) (Non-Patent Document 1). In healthy skin, normal stratum corneum peeling occurs when corneodesmosomes are degraded by proteases (Non-Patent Document 2). On the other hand, in dry skin, protease activity is reduced, and it is said that the decomposition of corneodesmosomes is inhibited, resulting in the accumulation of keratinocytes (Non-Patent Document 3). Accumulation of keratinocytes is also observed in senile xerosis. In addition, many skin diseases accompanied by abnormalities in the stratum corneum desquamation function have been reported, such as dandruff, ichthyosis vulgaris, sex-linked ichthyosis, and psoriasis (Non-Patent Documents 4 to 6).

[0004] In dry skin, xerosis, and various skin diseases as mentioned above, abnormalities are observed in the skin surface condition, and the skin texture is impaired. The associated concerns about appearance significantly reduce the emotional quality of life, so technology to improve skin texture is important not only from a cosmetic perspective, but also for people to maintain a healthy lifestyle.

[0005] One such improvement technology that has been reported so far is the use of carbon dioxide as an active ingredient to improve the skin's stratum corneum desquamation function and to quickly improve the skin surface shape, based on the fact that carbon dioxide has the effect of activating stratum corneum desquamating enzymes and promoting the decomposition of corneodesmosomes (Patent Document 1).

[0006] On the other hand, Senrenshi (Chinese elm) is a herbal medicine made by drying the fruit of the Tousensis genus of the Meliaceae family, and is known to have sedative, analgesic, and anthelmintic effects. Extracts of Tousensis have also been reported to have whitening and moisturizing effects (Patent Documents 2 and 3). However, nothing is known about the effect of Tousensis extracts on the skin's stratum corneum desquamation function or the effect of Tousensis extracts on the stratum corneum desquamation-improving effect of carbon dioxide gas. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] JP 2019-214520 A [Patent Document 2] JP 2010-195732 A [Patent Document 3] JP 2011-79754 A [Non-patent literature]

[0008] [Non-Patent Document 1] Borgono CA, et al., A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. J Biol Chem. 282(6): 3640-3652 (2007) [Non-Patent Document 2] Kubo A. et al., Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J Clin Invest. 122(2): 440-447 (2012) [Non-Patent Document 3] Rawlings AV. et al., Skin biology, xerosis, barrier repair and measurement Drug Discovery Today. 5(2): e127-e136 (2008) [Non-Patent Document 4] Singh B. et al., Retention of corneodesmosomes and increased expression of protease inhibitors in dandruff. Br J Dermatol. 171(4): 760-770 (2014) [Non-Patent Document 5] Kitajima Y. et al., Implications of normal and disordered remodeling dynamics of corneodesmosomes in stratum corneum. Dermatologica Sinica. 33(2): 58-63 (2015) [Non-Patent Document 6] Simon M. et al., Alterations in the desquamation-related proteolytic cleavage of corneodesmosin and other corneodesmosomal proteins in psoriatic lesional epidermis. Br J Dermatol. 159(1): 77-85 (2008) Summary of the Invention [Problem to be solved by the invention]

[0009] The present invention relates to providing a technique for improving the stratum corneum peeling function of the skin and improving the texture of the skin. [Means for solving the problem]

[0010] As a result of intensive research in light of the above problems, the inventors have found that although an extract of Tosendan alone does not exhibit the effect of promoting the decomposition of corneodesmosomes, when used in combination with carbon dioxide, it is possible to enhance the effect of carbon dioxide in promoting the decomposition of corneodesmosomes.

[0011] That is, the present invention relates to the following 1) to 5). 1) A stratum corneum peeling improvement agent whose active ingredients are carbon dioxide gas and extract of Tosendan. 2) A stratum corneum intercellular adhesion protein decomposition promoter, whose active ingredients are carbon dioxide gas and an extract of Tosendan. 3) A skin texture improver whose active ingredients are carbon dioxide gas and extract of Tosendan. 4) An enhancer for improving the peeling action of carbon dioxide gas, containing an extract of Tosendan as the active ingredient. 5) An enhancer for promoting the decomposition of intercellular adhesion proteins in the stratum corneum by carbon dioxide, containing an extract of Tosendan as its active ingredient. Effect of the Invention

[0012] According to the present invention, application of carbon dioxide gas and an extract of Tosendan to the skin enhances the effect of carbon dioxide gas in promoting the decomposition of intercellular adhesion proteins in the stratum corneum, effectively normalizing stratum corneum desquamation, promoting healthy stratum corneum formation, and improving skin texture. [Brief description of the drawings]

[0013] [Figure 1] This figure shows the results of histological observation by fluorescent immunostaining on the effects of Tosendan extract, carbon dioxide, or a combination of carbon dioxide and Tosendan extract on DSG1 expression in 3D cultured epidermis (in the figure, the white dashed line indicates the position of the outermost layer of the epidermis, and the white area in the epidermis indicates the area of ​​fluorescent signal for DSG1). [Diagram 2] FIG. 2 shows the results of quantifying the fluorescent signal derived from DSG1 in the epidermis in the histological observation by fluorescent immunostaining in FIG. 1 (relative values ​​assuming the fluorescent signal amount in the control group to be 1). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] All patents, non-patent publications, and other publications cited herein are hereby incorporated by reference in their entirety.

[0015] As shown in the Examples below, when carbon dioxide gas and an extract of Tosendan are applied to human 3D cultured epidermis, enhanced decomposition of desmoglein 1 (DSG1) in the stratum corneum is observed compared to when either is applied alone. Carbon dioxide gas is known to have an effect of promoting the decomposition of DSG1 in the stratum corneum (Patent Document 1). However, since the extract of Tosendan alone does not have an effect of promoting DSG1 decomposition, it is clear that such an effect is obtained by the extract of Tosendan enhancing the effect of carbon dioxide gas in promoting DSG1 decomposition. In addition, when a composition containing carbon dioxide gas and an extract of Tosendan is applied to human skin, improvement in the texture of the skin, represented by skin smoothness, moistness, and softness, is observed. As mentioned above, in healthy skin, it is believed that normal stratum corneum desquamation occurs when intercellular adhesion proteins such as DSG1, which constitute the adhesion structures (corneodesmosomes) between stratum corneum cells, are cleaved and degraded by stratum corneum desquamating enzymes (Non-Patent Document 2). From these findings, the combination of carbon dioxide gas and extract of Tosendan has the effect of promoting the decomposition of stratum corneum intercellular adhesion proteins, improving stratum corneum desquamation, and improving skin texture. In addition, extract of Tosendan has the effect of enhancing the effect of carbon dioxide gas in promoting the decomposition of stratum corneum intercellular adhesion proteins and enhancing the effect of improving stratum corneum desquamation.

[0016] Therefore, the combination of carbon dioxide gas and Tosendan extract can be an agent for promoting the decomposition of stratum corneum intercellular adhesion proteins, an agent for improving stratum corneum delamination, and an agent for improving skin texture (hereinafter also referred to as "stratum corneum delamination improving agent, etc."), and can be used to produce these. By supplying the combination of carbon dioxide gas and Tosendan extract to human skin, it is possible to promote the decomposition of stratum corneum intercellular adhesion proteins, improve stratum corneum delamination, and improve skin texture. The combination of carbon dioxide gas and Tosendan extract can be used to promote the decomposition of stratum corneum intercellular adhesion proteins, improve stratum corneum delamination, and improve skin texture. Furthermore, the extract of Tosendan can be an enhancer of the action of carbon dioxide gas promoting the decomposition of intercellular adhesion proteins in stratum corneum, and an enhancer of the action of carbon dioxide gas improving stratum corneum desquamation (hereinafter also referred to as "enhancer of the action of carbon dioxide gas improving stratum corneum desquamation, etc."), and can be used to produce these. By supplying the extract of Tosendan to human skin, the action of carbon dioxide gas promoting the decomposition of intercellular adhesion proteins in stratum corneum can be enhanced, and the action of carbon dioxide gas improving stratum corneum desquamation can be enhanced. The extract of Tosendan can be used to enhance the action of carbon dioxide gas promoting the decomposition of intercellular adhesion proteins in stratum corneum, and to enhance the action of carbon dioxide gas improving stratum corneum desquamation.

[0017] Here, the combination of carbon dioxide gas and an extract of Tosendan serrata or the use of the extract of Tosendan serrata on humans may be therapeutic use, but may also be non-therapeutic use. "Non-therapeutic" is a concept that does not include medical procedures, i.e., does not include methods of surgery, treatment, or diagnosis on humans, more specifically, does not include methods of surgery, treatment, or diagnosis on humans by doctors, medical professionals, or those under the instructions of doctors. In the present invention, non-therapeutic use includes the combination of carbon dioxide gas and an extract of Tosendan serrata or the use of the extract of Tosendan serrata for cosmetic or aesthetic purposes to improve stratum corneum peeling, for example, use by estheticians, hairdressers, barbers, trimmers, etc.

[0018] In the present invention, "intercellular adhesion protein" means a protein that constitutes the adhesive structure (corneodesmosome) between corneoblasts, and examples thereof include desmoglein 1 (DSG1), desmocollin 1 (DSC1), corneodesmosin (CDSN), etc., preferably DSG1. In the present invention, "stratum corneum desquamation" means that the adhesive mechanism between stratum corneum cells weakens, causing old stratum corneum cells to peel off from the skin surface, and improvement therein means suppressing the delay in stratum corneum desquamation or promoting or normalizing stratum corneum desquamation. In the present invention, "improvement of skin texture" refers to suppression or improvement of deterioration of skin condition evaluated by touch, specifically, improvement of skin texture through healthy stratum corneum formation by improvement of stratum corneum peeling. Examples of skin texture include smoothness, moistness, softness, etc., and preferably smoothness. Here, smoothness of skin refers to a slippery feeling or a smooth feeling when touching the skin surface with a finger, moistness refers to skin that contains moderate moisture and is moisturized, and softness refers to skin that is soft. Skin texture can be evaluated by sensory evaluation, for example, by a professional judge scoring according to various evaluation criteria. Alternatively, in instrumental measurement, for example, smoothness can be evaluated using the coefficient of friction on the skin surface, moistness can be evaluated using the moisture content of the stratum corneum, and softness can be evaluated using the hardness or elasticity coefficient of the skin as an index. Improvement of skin texture can be judged based on the magnitude of the score and the magnitude of the measured values ​​of various indexes in instrumental measurement. Alternatively, the degree of improvement in skin texture can be qualitatively evaluated, for example, by compiling the results of a questionnaire in a home use test.

[0019] In the present invention, the term "tooshen" refers to Melia toosendan Sieb. et Zucc., which belongs to the Meliaceae family and the Melia genus. Dried fruits of the tooshen are known as a herbal medicine called Senrenshi.

[0020] Any part of the Tosendan used in the present invention can be used. For example, the whole tree or any part (root, rhizome, trunk, branch, stem, leaf, bark, sap, resin, flower, fruit, seed, pericarp, pod, bud, spike, heartwood, etc.), or any combination thereof can be used. Among these, it is preferable to use the fruit. When using the fruit of Tosendan, the herbal medicine Senrenshi can also be used.

[0021] There is no particular limitation on the method for producing the extract of Tosendan, and the extract can be obtained by extracting Tosendan by a normal method. Specifically, the extract of Tosendan in the present invention can be a dried product of Tosendan, a squeezed juice obtained by squeezing and extracting a pulverized product thereof, a steam distillate, a crude extract using various extraction solvents, or an extract fraction obtained by purifying a crude extract by partitioning or various chromatographies such as column chromatography. Although it is possible to subject the tosendan to extraction in its raw form, it is also preferable to add a step such as drying, shredding, or crushing in order to improve the extraction efficiency. In addition, in the present invention, the above-mentioned extract, steam distillate, squeezed product, etc. may be used alone or in combination of two or more. Among them, as the tosendan extract of the present invention, it is more preferable to use an extract obtained from a dried product obtained by drying the tosendan or its crushed product using an extraction solvent, and it is even more preferable to use an extract obtained from Senrenshi using an extraction solvent.

[0022] As the extraction solvent, either polar or non-polar solvents can be used, and these can also be used in combination. For example, water; monohydric alcohols such as methanol, ethanol, propanol, and butanol; polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and polyethylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate; linear and cyclic ethers such as tetrahydrofuran and diethyl ether; polyethers such as polyethylene glycol; halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; hydrocarbons such as hexane, cyclohexane, and petroleum ether; aromatic hydrocarbons such as benzene and toluene; pyridines; supercritical carbon dioxide; oils and fats, waxes, and other oils. Alternatively, a mixture of two or more of the above solvents can be used as the extraction solvent. Among these, it is preferable to use water, monohydric or polyhydric alcohols, or a water-monohydric or polyhydric alcohol mixture, it is more preferable to use monohydric or polyhydric alcohols, or a water-monohydric or polyhydric alcohol mixture, and it is even more preferable to use monohydric or polyhydric alcohols. Here, as the monohydric or polyhydric alcohols, it is preferable to use ethanol, propylene glycol, or 1,3-butylene glycol, it is more preferable to use ethanol or 1,3-butylene glycol, and it is even more preferable to use ethanol.

[0023] The extraction conditions for obtaining the extract of Tosendan used in the present invention vary depending on the solvent used and are not particularly limited, but for example, when extracting with water, monohydric or polyhydric alcohols, or a water-monohydric or polyhydric alcohol mixture, it is preferable to use 1 to 50 parts by volume of the solvent per 1 part by mass of Tosendan, and to immerse or heat reflux at a temperature of preferably 3 to 100° C., more preferably 20 to 80° C., preferably for 1 hour to several weeks, more preferably for 1 day to 30 days. In addition, in order to increase the extraction efficiency, stirring or homogenization treatment in the solvent may be performed.

[0024] The extract of Tosendan obtained by extraction with the above-mentioned solvent may be used as it is, but it can also be used after fractionating a highly active fraction by a suitable separation means, such as gel filtration, chromatography, precision distillation, etc. In the present invention, the extract of Tosendan includes various extracts thus obtained, their dilutions, their concentrates, their purified products, or their dried powders.

[0025] The means for the stratum corneum peeling improving agent of the present invention is not particularly limited as long as it can supply carbon dioxide gas and an extract of Tosendan to the stratum corneum. Either the carbon dioxide gas or the extract of Tosendan may be administered first, or they may be administered simultaneously. When they are not administered simultaneously, the administration interval between the two may be appropriately selected as long as the effect of enhancing the stratum corneum peeling improving action of carbon dioxide gas is exhibited. The agent comprising a combination of carbon dioxide gas and an extract of Tosendan may be a formulation in which carbon dioxide gas and an extract of Tosendan are combined into a single dosage form, or may be a kit in which the two are individually formulated and used simultaneously or separately at intervals. A single dosage form formulation containing both carbon dioxide gas and an extract of Tosendan may be used.

[0026] The stratum corneum peeling improving agent of the present invention is preferably an aerosol cosmetic preparation containing carbon dioxide gas as a propellant (JP 2014-129306 A, JP 2017-125003 A, etc.), a foaming cosmetic preparation containing a carbon dioxide gas generator that reacts with water to generate carbon dioxide gas, a nonwoven sheet (JP 2015-105451 A), a bath additive (JP 9-2942 A, JP 2000-191429 A, etc.), a pad (JP 2006-249025 A, etc.), etc., which is capable of supplying carbon dioxide gas to the stratum corneum of the skin and further contains an extract of Tosendan. Among them, an aerosol preparation such as an aerosol cosmetic preparation containing an extract of Tosendan and containing carbon dioxide gas as a propellant in an external preparation for skin (undiluted solution) is more preferable.

[0027] When carbon dioxide gas is encapsulated in an external skin preparation as a propellant, from the viewpoint of obtaining the stratum corneum peeling improving effect of the present invention on the skin, it is preferable that the propellant contains 90% by mass or more of carbon dioxide gas, more preferably 95% by mass or more, even more preferably 98% by mass or more, and even more preferably 100% by mass.

[0028] When preparing an aerosol preparation containing carbon dioxide gas as a propellant, the mass ratio of the skin topical preparation (undiluted solution) to the propellant containing carbon dioxide gas is preferably 94:6 to 99.5:0.5, more preferably 95:5 to 99:1, and even more preferably 96.5:3.5 to 98.5:1.5. The form of spray of the aerosol preparation is preferably a foam type in which the skin topical preparation is discharged in the form of foam, from the viewpoint of allowing the carbon dioxide gas blended as a propellant to remain continuously on the skin.

[0029] The content of the extract of Tosendan in the skin external preparation used as the stock solution is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.001% by mass or more, preferably 20% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, even more preferably 0.1% by mass or less, even more preferably 0.01% by mass or less. The content of the extract of Tosendan in the stock solution is preferably 0.00001 to 20% by mass, more preferably 0.0001 to 10% by mass, even more preferably 0.001 to 5% by mass, even more preferably 0.001 to 1% by mass, even more preferably 0.001 to 0.1% by mass, even more preferably 0.001 to 0.01% by mass. In this specification, the content of the extract of Tosendan is meant the content of the extract of Tosendan in terms of dry solid content.

[0030] In an aerosol preparation (aerosol cosmetic) in which carbon dioxide gas is enclosed as a propellant, the blending ratio of carbon dioxide gas to extract of Tosendan (carbon dioxide gas / extract of Tosendan) is preferably 600,000 to 0.025, more preferably 5,000 to 0.1, even more preferably 3,500 to 0.3, even more preferably 2,000 to 1, and even more preferably 1,000 to 30, in mass ratio.

[0031] The skin topical preparation used as the concentrate may further contain various ingredients that are normally used in skin topical preparations such as cosmetics, quasi-drugs, and pharmaceuticals. Specifically, from the viewpoint of discharging the skin topical preparation in a foam form, improving the spread of the foam on the skin, providing an excellent feeling of use, sustaining the foam, and enhancing the effect of carbon dioxide, it is preferable to contain ingredients such as powder, oil, surfactant, water-soluble thickener, and water. In addition, as ingredients that are normally used in cosmetics, for example, ethanol, blood circulation promoters, cooling agents, antiperspirants, bactericides, whitening agents, anti-inflammatory agents, skin activators, moisturizers, moisturizers, preservatives, antioxidants, chelating agents, thickeners, ultraviolet absorbers, emulsion stabilizers, pH adjusters, colorants, and fragrances may also be added.

[0032] The powder may be one or more powders selected from silicon oxide, titanium oxide, zinc oxide, talc, mica, (meth)acrylic acid or its salt / (meth)acrylic acid alkyl crosspolymer, and silicone elastomer having an average particle size of 0.01 to 30 μm. Among the above powders, silicon oxide is particularly used in the present invention. The silicon oxide used in the present invention has an average particle size of 0.25 to 20 μm, and preferably 0.25 to 10 μm in terms of providing a better feeling of use. This powder is not soluble in water, alcohol, oil, etc. The shape of the powder may be any of spherical, plate-like, etc. There is no limitation on the internal structure of the powder, and any of porous, hollow, non-porous, etc. can be used. From the viewpoint of the feel, the powder is preferably spherical. In the present invention, the average particle size is measured using a laser diffraction scattering type particle size distribution measuring device LA-920 / HORIBA / median size.

[0033] The silicon oxide used in the present invention is not limited as long as it is one that is commonly used in cosmetics, and may be modified powders whose surfaces have been treated with compounds, those that have not been hydrophobized with silicone oil, fatty acid metal salts, or those that have a hydrophilic surface.Specifically, commercially available products include Sunsphere NP-30, NP-100, H-31 (AGC Si-Tech Co., Ltd.), Sylopure 35 (Fuji Silysia Chemical Co., Ltd.), and HCS 160M5 (Ikeda Bussan Co., Ltd.).NP-30 is more preferred in terms of providing a better feeling of use.

[0034] The content of the powder in the concentrate is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, and preferably 2.5% by mass or less, more preferably 2.0% by mass or less, and even more preferably 1.5% by mass or less, from the viewpoint of improving the uniform application of the foam containing carbon dioxide gas to the skin and the permeability of the carbon dioxide gas into the skin. The specific content range is preferably 0.001 to 2.5% by mass, more preferably 0.005 to 2.0% by mass, and even more preferably 0.01 to 1.5% by mass.

[0035] The oil agent is not limited as long as it is one that is commonly used in cosmetics, and examples thereof include hydrocarbon oils, silicone oils, ester oils, ether oils, and fluorine oils. More specifically, examples of liquids at 25°C include silicone oils such as methylpolysiloxane, hydrocarbons such as paraffin, squalane, and squalene; natural animal and vegetable oils mainly composed of triglycerides such as camellia oil, jojoba oil, olive oil, macadamia nut oil, avocado oil, and olive oil; glycerin monostearate, glycerin distearate, glycerin monooleate, isopropyl palmitate, isopropyl stearate, butyl stearate, isopropyl myristate, diethyl phthalate, myristyl lactate, cetyl myristate, cetyl lactate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, 2-octyldodecyl myristate, 2-octyldodecyl oleate, glycerol triisostearate, di-paramethoxycinnamate-mono-2- Examples of such oils include monoester oils such as glyceryl ethylhexanoate, isotridecyl isononanoate, glyceryl monoisostearate and monomyristate, and alkyl benzoate (alkyl groups having 12 to 15 carbon atoms); diester oils such as diisopropyl adipate, diisobutyl adipate, neopentyl glycol dicaprate, glyceryl tri(caprylate-caprate), glycerin tricaprate, neopentyl glycol di-2-ethylhexanoate, di(caprylate / caprate)propanediol, 1-isostearoyl-3-myristoyl glycerol, diisostearyl malate, and di(cholesteryl-octyldodecyl) N-lauroyl-L-glutamate; ether oils such as alkyl-1,3-dimethylbutyl ether, dicaprylyl ether, and dicaprylyl ether; and essential oils such as eucalyptus oil and peppermint oil. Among these, monoester oils and diester oils are preferred, and isotridecyl isononanoate and alkyl benzoate are more preferred, from the viewpoint of increasing the carbon dioxide gas concentration and imparting a smooth feeling of use. In addition, examples of oils other than those that are liquid at 25° C. include waxes, pastes and solid fats that are solid at 25° C., such as higher alcohols having 12 to 24 carbon atoms, higher fatty acids having 12 to 24 carbon atoms, and paraffin wax. From the viewpoint of improving the permeability of carbon dioxide gas into the skin, the viscosity of the oil is 1 mPa·s or more, preferably 2 mPa·s or more, more preferably 3 mPa·s or more, even more preferably 4 mPa·s or more, and 100 mPa·s or less, preferably 50 mPa·s or less, more preferably 30 mPa·s or less, and even more preferably 20 mPa·s or less. The oil has a viscosity of 1 to 100 mPa·s, preferably 2 to 50 mPa·s, more preferably 3 to 30 mPa·s, and even more preferably 4 to 20 mPa·s. Here, the viscosity is measured at 25° C. using a BM viscometer (manufactured by Toki Sangyo Co., Ltd.) (rotor No. 1, 60 rpm, 1 minute).

[0036] One or more oils may be used, and from the viewpoint of improving the permeability of carbon dioxide gas into the skin and the film-like feel on the skin after application, the content is 1% by mass or more in the concentrate, preferably 2% by mass or more, more preferably 4% by mass or more, and 25% by mass or less, preferably 15% by mass or less, and more preferably 12% by mass or less. The content of the oil in the concentrate is 1 to 25% by mass, preferably 2 to 15% by mass, and more preferably 4 to 12% by mass.

[0037] Examples of the surfactant include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants, but nonionic and anionic surfactants are preferably used from the viewpoints of the amount of carbon dioxide dissolved in the original solution, solubility promotion, and foaming during application. The nonionic surfactant used in the present invention is a nonionic surfactant with an HLB of 3 to 20, and the HLB of the nonionic surfactant is preferably 7 or more, more preferably 9 or more, and even more preferably 11 or more from the viewpoints of improving the penetration feeling of the foam into the skin and the storage stability of the composition, and is preferably 18 or less, more preferably 16 or less, and even more preferably 15 or less from the viewpoint of improving the film feeling of the skin after application. In addition, the HLB of the nonionic surfactant is preferably 7 to 18, more preferably 9 to 16, and even more preferably 11 to 15. Here, HLB (Hydrophilic-Lipophilic Balance) indicates the molecular weight of the hydrophilic group in the total molecular weight of the surfactant, and is calculated by Griffin's formula. The HLB of a mixed surfactant consisting of two or more nonionic surfactants is calculated by averaging the HLB values ​​of each nonionic surfactant based on their blending ratio.

[0038] Specific examples of the nonionic surfactant include sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oil, and the like. Polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene hydrogenated castor oil are preferred, sorbitan fatty acid esters and polyoxyethylene hydrogenated castor oil are more preferred, and polyoxyethylene hydrogenated castor oil is even more preferred. From the viewpoint of improving the permeability of carbon dioxide gas into the skin and the stability of foam, the polyoxyethylene hydrogenated castor oil preferably has an average added mole number of ethylene oxide of 20 to 90, more preferably 30 to 80, and even more preferably 50 to 70.

[0039] The nonionic surfactant may be used alone or in combination of two or more, and the content thereof in the concentrate is 0.05% by mass or more, preferably 0.1% by mass or more, more preferably 0.3% by mass or more, and 6% by mass or less, preferably 2% by mass or less, and more preferably 1% by mass or less, from the viewpoint of improving the spread of the foam, the permeability of the carbon dioxide gas into the skin, and the film-like feel on the skin after application. The content of the nonionic surfactant in the concentrate is 0.05 to 6% by mass, preferably 0.1 to 2% by mass, and more preferably 0.3 to 1% by mass.

[0040] The water-soluble thickener may be any one used in ordinary cosmetics, such as carrageenan, dextrin, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, carboxyvinyl polymer, (acrylic acid / alkyl acrylate (C10-30)) copolymer, xanthan gum, carboxymethyl chitin, chitosan, etc. Among these, from the viewpoints of suppressing the volatilization of carbon dioxide gas, the stability of the original solution, and the feeling of use during and after application (non-stickiness, smoothness, and softness), acrylic acid-based polymers are preferred, carboxyvinyl polymers and acrylic acid / alkyl acrylate copolymers are more preferred, and (acrylic acid / alkyl acrylate (C10-30)) copolymers are more preferred. Here, the (acrylic acid / alkyl acrylate (C10-30)) copolymer is a copolymer of C10-30 alkyl acrylic acid and acrylic acid, methacrylic acid or lower alkyl esters thereof, crosslinked with sucrose allyl ether or pentaerythritol allyl ether, and commercially available products such as Pemulen TR-1, Pemulen TR-2, Carbopol ETD2020, Carbopol 1342, and Carbopol 1382 (all from Lubrizol Advanced Materials) can be used. In addition, it is preferable to use an alkali metal hydroxide such as potassium hydroxide or sodium hydroxide as a neutralizing agent for an acid-type water-soluble thickener such as polyacrylic acid, carboxyvinyl polymer, or (acrylic acid / alkyl acrylate (C10-30)) copolymer as a water-soluble or water-dispersible salt.

[0041] The water-soluble thickener may be one or a combination of two or more selected from the above, and the content thereof in the stock solution is 0.05% by mass or more, preferably 0.1% by mass or more, more preferably 0.2% by mass or more, and 1% by mass or less, preferably 0.8% by mass or less, and more preferably 0.7% by mass or less, from the viewpoint of improving non-stickiness during application and stability of the stock solution. The content of the water-soluble thickener in the stock solution is 0.05 to 1% by mass, preferably 0.1 to 0.8% by mass, and more preferably 0.2 to 0.7% by mass.

[0042] Water acts as a solvent, and is preferably 55% by mass or more, more preferably 60% by mass or more, and even more preferably 65% ​​by mass or more in the original solution, and is preferably 95% by mass or less, more preferably 93% by mass or less, and even more preferably 90% by mass or less in the original solution. The content of water in the original solution is preferably 55 to 95% by mass, more preferably 60 to 93% by mass, and even more preferably 65 to 90% by mass.

[0043] From the viewpoint of improving stability, foam ejection, and carbon dioxide gas permeability into the skin, the viscosity of the concentrate at 25°C is preferably 500 mPa·s or more, more preferably 1000 mPa·s or more, even more preferably 1500 mPa·s or more, and preferably 20000 mPa·s or less, more preferably 15000 mPa·s or less, and even more preferably 10000 mPa·s or less. The viscosity of the concentrate at 25°C is preferably 500 to 20000 mPa·s, more preferably 1000 to 15000 mPa·s, and even more preferably 1500 to 10000 mPa·s. Here, the viscosity was measured at 25°C using a BM viscometer (manufactured by Toki Sangyo Co., Ltd.) with rotor No. 3, 12 rpm, and 1 minute. When the viscosity exceeded 10,000 mPa s, the value was measured with rotor No. 3, 6 rpm, and 1 minute.

[0044] The carbon dioxide gas generating agent used in the foaming skin preparation for external use is usually a preparation which comprises a carbon dioxide gas generating substance and an acidic substance, and which reacts with water to generate carbon dioxide gas. Here, the acidic substance may be either an inorganic acid or an organic acid, and one or more of these may be used. Examples of the organic acid include one or more selected from succinic acid, fumaric acid, malic acid, adipic acid, tartaric acid, benzoic acid, citric acid, pyrrolidone carboxylic acid, and salicylic acid. Examples of the inorganic acid include one or more selected from phosphoric acid, boric acid, metasilicic acid, and silicic anhydride. Among them, from the viewpoint of ensuring the amount of carbon dioxide gas generated, organic acids are preferred, and one or more selected from citric acid, malic acid, fumaric acid, succinic acid, and tartaric acid are more preferred, and one or two selected from citric acid, malic acid, and fumaric acid are even more preferred.

[0045] The carbon dioxide gas generating substance may be a carbonate, specifically, for example, one or more selected from sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, calcium carbonate, magnesium carbonate, and sodium sesquicarbonate. Among them, the carbonate is preferably one or more selected from sodium carbonate and sodium hydrogen carbonate from the viewpoint of ensuring the amount of carbon dioxide gas generated.

[0046] Such a carbon dioxide gas generating agent may contain the acidic substance and the carbon dioxide gas generating substance in the same agent, or may contain them separately in a plurality of agents.

[0047] The content of the extract of Tosendan in the foaming skin topical preparation is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.001% by mass or more, preferably 20% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, even more preferably 0.1% by mass or less, even more preferably 0.01% by mass or less. The content of the extract of Tosendan is preferably 0.00001-20% by mass, more preferably 0.0001-10% by mass, more preferably 0.001-5% by mass, even more preferably 0.001-1% by mass, even more preferably 0.001-0.1% by mass, even more preferably 0.001-0.01% by mass.

[0048] The foaming skin topical preparation may be in any form, such as solid, liquid, or gel. In the case of a solid form, it may be in the form of granules, fine particles, or powder. The skin topical preparation may be in any form, such as a cosmetic, quasi-drug, or pharmaceutical, but is preferably used as a cosmetic or quasi-drug. Specifically, it may be in various forms, such as a lotion, milky lotion, beauty gel, pack, hair growth agent, face wash, cleansing agent, shampoo, and conditioner, and is preferably used by mixing with a water-containing substance on the palm or in a container and foaming it.

[0049] An example of a nonwoven fabric sheet is a sheet that carries a powdered carbon dioxide gas generating agent (an acidic substance and a carbon dioxide gas generating substance) and an extract of Tosendan, and that can generate a sufficient amount of carbon dioxide gas on the skin where the sheet is attached and supply a sufficient amount of Tosendan extract by simply pouring water or hot water onto the nonwoven fabric sheet attached to the skin. Specific examples of the present invention include (A) powders selected from organic acids and inorganic acids, (B) powders which are carbonates, (C) substances having a melting point of 50°C or higher and 110°C or lower and which are solid at 25°C (for example, polymeric compounds such as polyethers such as polyethylene glycol and cellulose derivatives such as hydroxyethyl cellulose; higher fatty acids such as myristic acid and palmitic acid; higher alcohols such as cetyl alcohol, hexadecyl alcohol, cetearyl alcohol, and stearyl alcohol; and sugars such as glucose and maltose), and (D) nonwoven fabric sheets containing fibers (JP Patent Publication No. 2015-105451 A) further containing an extract of Tosendan.

[0050] The amount of extract of Tosendan was determined based on the amount of carbon dioxide gas per 1 m of the nonwoven fabric sheet, in order to enhance the effect of carbon dioxide gas on the skin in improving the peeling of the stratum corneum. 2 The content of the extract of Tosendan is preferably 0.000005g or more, more preferably 0.00005g or more, even more preferably 0.0005g or more, and is preferably 200g or less, more preferably 100g or less, even more preferably 50g or less, even more preferably 10g or less, even more preferably 1g or less, and even more preferably 0.1g or less per 1m of the nonwoven fabric sheet. 2 The amount is preferably 0.000005 to 200 g, more preferably 0.00005 to 100 g, even more preferably 0.0005 to 50 g, still more preferably 0.00005 to 10 g, even more preferably 0.00005 to 1 g, and still more preferably 0.00005 to 0.1 g.

[0051] Examples of bath additives include effervescent tablet-type bath additives (JP Patent Publication No. 9-2942 A) which contain (a) a solid excipient containing 10% by weight or more of a surfactant and at least twice the weight of the surfactant in a carbonate salt, (b) a carbonate or bicarbonate salt, and (c) an organic acid, and in which the content of component (a) in the bath additive is 3 to 20% by weight (A) (Japanese Patent Publication No. 2000-191429 A), and which further contain an extract of Tosendan.

[0052] From the viewpoint of enhancing the stratum corneum peeling improving action of carbon dioxide gas on the skin, the content of the extract of Tosendan is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, even more preferably 0.001% by weight or more, preferably 20% by weight or less, more preferably 10% by weight or less, even more preferably 5% by weight or less, even more preferably 1% by weight or less, even more preferably 0.1% by weight or less, even more preferably 0.01% by weight or less. The content of the extract of Tosendan is preferably 0.00001-20% by weight, more preferably 0.0001-10% by weight, even more preferably 0.001-5% by weight, even more preferably 0.001-1% by weight, even more preferably 0.001-0.1% by weight, even more preferably 0.001-0.01% by weight.

[0053] Examples of pads include a pad that comprises a water-absorbent base layer, a protective layer with gas barrier properties that is arranged to cover the base layer, and a carbon dioxide gas generating agent enclosed between the protective layer and the base layer, and that can be attached to the skin at the peripheral portion of the protective layer (JP Patent Publication No. 2006-249025), in which the carbon dioxide gas generating agent is further blended with an extract of Tosendan.

[0054] The means for enhancing the stratum corneum delamination-improving effect of carbon dioxide gas of the present invention is not particularly limited as long as it can supply the extract of Tosendan to the stratum corneum of the skin. The enhancer for improving stratum corneum delamination of carbon dioxide gas of the present invention may be administered prior to, simultaneously with, or after administration of carbon dioxide gas. When the enhancer for improving stratum corneum delamination of carbon dioxide gas of the present invention and carbon dioxide gas are not administered simultaneously, the administration interval between the two may be appropriately selected as long as the effect of the enhancer for improving stratum corneum delamination of carbon dioxide gas of the present invention is exhibited.

[0055] The administration form of the enhancer of the stratum corneum peeling improving effect of carbon dioxide gas of the present invention may be solid, semi-solid or liquid, and is preferably a parenteral administration form such as a skin topical preparation or patch. More preferably, it is a skin topical preparation. Dosage forms include ointments, creams, gels, patches, ticks, liniments, lotions, sprays, etc. Such preparations in various dosage forms can be prepared by appropriately combining the active ingredient, an extract of Tosendan, with a pharmaceutical or cosmetically acceptable carrier, other medicinal or cosmetic ingredients, as necessary, by a general manufacturing method. Examples of the pharmaceutical or cosmetically acceptable carrier include water, oils, surfactants, solvents, thickeners, gelling agents, alcohols, chelating agents, emulsion stabilizers, pH regulators, salts, preservatives, antioxidants, ultraviolet absorbers, pigments, fragrances, etc. Examples of other medicinal or cosmetic ingredients include plant extracts, moisturizers, antibacterial agents, anti-inflammatory agents, cooling agents, makeup ingredients, etc.

[0056] The content of the extract of Tosendan in the above preparation varies depending on the form of use, but from the viewpoint of enhancing the stratum corneum peeling improving effect of carbon dioxide gas on the skin, it is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.001% by mass or more, preferably 20% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, even more preferably 1% by mass or less, even more preferably 0.1% by mass or less, even more preferably 0.01% by mass or less. The content of the extract of Tosendan in the above preparation is preferably 0.00001 to 20% by mass, more preferably 0.0001 to 10% by mass, even more preferably 0.001 to 5% by mass, even more preferably 0.001 to 1% by mass, even more preferably 0.001 to 0.1% by mass, even more preferably 0.001 to 0.01% by mass.

[0057] The stratum corneum peeling improving agent or the enhancer of the stratum corneum peeling improving effect of carbon dioxide gas of the present invention can be applied to the skin by spraying, painting, or the like according to any application schedule, and can be applied once to several times a day. The application period can be appropriately determined, and is, for example, preferably 1 day or more, more preferably 7 days or more, and even more preferably 14 days or more.

[0058] The subjects to which the stratum corneum desquamation improving agent of the present invention can be applied are not particularly limited as long as they are in need thereof, and examples thereof include people who aim to normalize stratum corneum desquamation, people who need to improve their skin texture, and people who wish to improve their skin texture. EXAMPLES

[0059] Example 1 Corneodesmosome degradation enhancement effect (1) Preparation of epidermis model The effects of Tosendan extract, carbon dioxide, and their combination on the skin's stratum corneum desquamation function were examined using LabCyte EPI-MODEL12 6D (J-TEC), a human 3D cultured epidermis model in which normal human epidermal cells are cultured in a layered manner. 1.0 mL of the medium provided with LabCyte EPI-MODEL12 6D was added to the outside of the culture cup, and the cells were cultured statically at 37°C in a 5% CO2 incubator for 24 hours.

[0060] (2) Addition of tosendan extract and application of carbon dioxide gas preparation As the extract of Tosendan, an extract of Tosendan containing 0.5% by mass of ethanol extract (dry solid content) of dried fruit of Tosendan (Kawa-enji), 79.75% by mass of 1,3-butylene glycol, and 19.75% by mass of purified water was used. As a control for the Tosendan extract, a solvent containing 79.75% by mass of 1,3-butylene glycol and 20.25% by mass of purified water (hereinafter referred to as the control solvent) was prepared.

[0061] The compositions of the carbon dioxide gas formulation and its control (formulation not containing carbon dioxide gas) are shown in Table 1 below. All raw materials were mixed at a temperature of 60°C while stirring the raw materials. First, Mekxance-M, potassium dihydrogen phosphate, and an appropriate amount of purified water were mixed and stirred. Next, PEMULEN TR-1 was mixed and stirred. To this, liquid caustic potash (48%) and purified water were appropriately mixed and stirred. Furthermore, all the remaining Emmanon CH60(K) and purified water were mixed and stirred. This was used as the stock solution shown in Table 1 below. Carbon dioxide gas was enclosed in this to make the carbon dioxide gas formulation (the ratio of stock solution to carbon dioxide gas was 97.8:2.2), and to the one without carbon dioxide gas enclosed was used as the non-carbon dioxide gas-containing formulation (stock solution only).

[0062] [Table 1]

[0063] This study was conducted in the following four groups. Control group: No application of Tosendan extract (control solvent application) and no application of carbon dioxide (non-carbon dioxide-containing formulation application) Tosendan extract group: Tosendan extract and no carbon dioxide gas (non-carbon dioxide gas-containing formulation) Carbon dioxide group: No use of Tosendan extract (control solvent) and use of carbon dioxide (use of carbon dioxide-containing preparation) Combination group: Use of tosendan extract and carbon dioxide gas (use of carbon dioxide gas-containing preparation) First, the above-mentioned extract of Tosendan was added to the attached medium to a final concentration of 0.3% to prepare a medium containing Tosendan extract (final concentration of Tosendan extract: 0.0015%, calculated as dry solids). For the non-application of Tosendan extract, a control solvent was added to the attached medium to a final concentration of 0.3% to prepare a medium containing a control solvent. Next, the medium on the outside of the culture cup of LabCyte EPI-MODEL12 6D was removed, and 1.0 mL of the prepared Tosendan extract-containing medium or control solvent-containing medium was added. This was returned to a 37°C, 5% CO2 incubator and cultured statically for 48 hours. After culture, 0.5 g of a carbon dioxide-containing formulation or a carbon dioxide-free formulation was applied to the surface of the epidermis model inside the culture cup. This was then cultured statically for 2 hours in a 37°C, 5% CO2 incubator.

[0064] (3) Preparation of sections After applying the carbon dioxide-containing or non-carbon dioxide-containing formulation and allowing to stand for 2 hours, the epidermis model was collected and embedded in OCT compound (Sakura Finetech Japan) to prepare a frozen block. The frozen block was sliced ​​to a thickness of 5 μm and attached to a slide glass.

[0065] (4) Immunostaining with anti-DSG1 antibody The slide glass was immersed in 100 mL of 4% paraformaldehyde-phosphate buffer (Fujifilm Wako Pure Chemical Industries, Ltd.) for 10 minutes to fix the tissue, and then immersed in 100 mL of 0.05% Tween (registered trademark)-20 / PBS (PBS-T) solution for 5 minutes and washed three times. To perform blocking treatment of the sections, the slides were arranged in a moist chamber (moist chamber, AS ONE), 100 μL of blocking solution (1% bovine serum albumin / PBS-T solution) was dropped onto the sections, and the sections were left to stand for 30 minutes. After 30 minutes, the blocking solution was removed, and 50 μL of anti-Desmoglein1 antibody (Progen Biotechnik., #651110) diluted 10-fold with the blocking solution was dropped onto the sections, and the sections were reacted at 4°C overnight (primary antibody reaction). The next day, the slides were immersed in 100 mL of PBS-T solution for 5 minutes, and washed three times. After washing, the slides were arranged in a moist chamber, and 50 μL of fluorescently labeled anti-mouse antibody (Jackson, #715-095-151) diluted 100-fold with the blocking solution was dropped onto the sections, and the sections were reacted at 37°C for 30 minutes (secondary antibody reaction). The slide glass was then immersed in 100 mL of PBS-T solution for 5 minutes, washed three times, and covered with a cover glass to seal it in. The sections were observed by taking images using a confocal laser microscope (LSM710, Carl Zeiss).

[0066] (5) Measurement of DSG1 signal The DSG1 signal was calculated using ImageJ (ver.1.53C) by the following method. First, the length of the bottom surface of the thin-sectioned tissue in the acquired image was measured. Next, the total brightness of the entire epidermal model was calculated. The total brightness of the entire epidermal model divided by the length of the bottom surface of the thin-sectioned tissue (total brightness (-) / length of the bottom surface of the thin-sectioned tissue (μm)) was used as the DSG1 signal. The DSG1 signal of the control group was set to 1, and the relative value of the DSG1 signal of each group was calculated to verify the effect of the Tosendan extract, the carbon dioxide-containing composition, and their combined use on DSG1 expression in the epidermal model.

[0067] (6) Results Figure 1 shows the immunostained images using anti-DSG1 antibodies for each group, and Figure 2 shows the DSG1 signal intensity for each group, expressed as a relative value with the control group set at 1. As shown in Figure 1, the fluorescent colored area of ​​DSG1 (white area in the epidermis) observed in the control group showed almost no change in the Tosendan extract group, but a decrease in the white area was observed in the carbon dioxide group, and the decrease was even more remarkable in the group treated with both carbon dioxide and Tosendan extract. This result was also reflected in the results of measuring the fluorescent color of DSG1, and as shown in Figure 2, the DSG1 signal was significantly attenuated by the combined use of carbon dioxide and Tosendan extract. From this result, it is considered that Tosendan extract alone does not show any DSG1 decomposition promoting effect, but when used in combination with carbon dioxide, it enhances the DSG1 decomposition promoting effect of carbon dioxide.

[0068] Example 2: Effect of improving skin texture (human test) (1) Evaluation method Eighteen healthy women aged 20 to 59 years were selected as the test participants, and for two weeks, twice a day, morning and night, before applying lotion, about 1 g (3 cm diameter when discharged) of a carbonic acid preparation (ratio of original solution to carbon dioxide gas: 97.8:2.2) containing 1% of the Tosendan extract of Example 1 as Tosendan extract (final concentration of Tosendan extract: 0.005%, calculated as dry solids) was applied to the entire face. After that, skin care was carried out as usual.

[0069] After the trial period ended, participants were asked to complete a questionnaire regarding the degree of improvement in skin texture compared to before the trial period began. The evaluation items were smoothness, moistness, and softness, and participants were asked to choose one of the following five options to indicate how they felt about "skin has become smoother," "skin has become moist," or "skin has become softer." The survey results of all trial participants were compiled to evaluate the degree of improvement in skin texture.

[0070] 1: I think so (improved) 2: I somewhat agree (somewhat improved) 3: Neither 4: Not really (it's gotten a little worse) 5: I don't think so (it's gotten worse)

[0071] The results are shown in Table 2. By applying carbon dioxide gas and Tosendan extract, more than 90% of the test subjects felt that the skin texture had improved in all evaluation items (selecting 1 or 2), with the improvement in skin smoothness being particularly excellent. From these results, it is believed that the combined use of carbon dioxide gas and Tosendan extract improved stratum corneum peeling, improving skin texture.

[0072] [Table 2]

Claims

1. A stratum corneum peeling improving agent containing carbon dioxide gas and an extract of Melia toosendan Sieb. et Zucc. as active ingredients.

2. A stratum corneum intercellular adhesion protein degradation promoter containing carbon dioxide and an extract of Tosendan as active ingredients.

3. A skin texture improver whose active ingredients are carbon dioxide gas and extract of Tosendan.

4. An enhancer of the stratum corneum peeling-improving effect of carbon dioxide gas, with an extract of Tosendan as the active ingredient.

5. An enhancer of carbon dioxide's effect of promoting the degradation of intercellular adhesion proteins in the stratum corneum, with an extract of the Japanese laurel tree as the active ingredient.

6. The agent for promoting the degradation of stratum corneum intercellular adhesion proteins according to claim 2 or the agent for enhancing the effect of carbon dioxide gas in promoting the degradation of stratum corneum intercellular adhesion proteins according to claim 5, wherein the stratum corneum intercellular adhesion protein is desmoglein 1.

7. The agent for improving stratum corneum peeling, the agent for promoting degradation of stratum corneum intercellular adhesion proteins, or the agent for improving skin texture according to any one of claims 1 to 3, which is an aerosol formulation.

8. The stratum corneum peeling improving agent, stratum corneum intercellular adhesion protein degradation promoter or skin texture improving agent according to claim 7, wherein the blending ratio of carbon dioxide gas to tosendan extract (carbon dioxide gas / tosendan extract) in the aerosol formulation is 600,000 to 0.025 in mass ratio.

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