JP6997890B2 - External composition for skin - Google Patents

Description

The present invention relates to an external composition for skin containing a poorly water-soluble component.

External skin medicines and skin cosmetics contain various physiologically active ingredients and cosmetic ingredients that act on the skin.
As one of the means for applying various physiologically active ingredients and cosmetic ingredients that act on the skin, a technique for supporting a drug or an oily ingredient on nanofibers and applying it to the skin has been reported. For example, Patent Document 1 discloses a method in which an oily component is supported on a hollow portion of nanofibers and applied to the skin. Further, Patent Document 2 discloses a technique for dispersing a drug in nanofibers.

Japanese Unexamined Patent Publication No. 2012-12714 Japanese Unexamined Patent Publication No. 2014-55119

The methods described in Patent Documents 1 and 2 merely support a drug or the like in nanofibers, and do not improve the applicability of the poorly water-soluble component to the skin.
Therefore, the present invention relates to a composition for external use on the skin, which immobilizes a poorly water-soluble component in a fine particle diameter and in an amorphous state and has excellent applicability to the skin.

The present invention relates to a fiber aggregate containing a component (a) a polymer soluble in water and an alcohol or a ketone, and a component (b) a poorly water-soluble component.
The fiber aggregate preferably contains the component (a) in an amount of 50% by mass or more and 98% by mass or less with respect to the entire fiber aggregate.
The fiber aggregate preferably contains the component (b) in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
The fiber aggregate is preferably a fiber aggregate for producing a liquid skin external composition.

The present invention also relates to a kit comprising a fiber aggregate and an aqueous medium.
The present invention also relates to a method for applying a liquid composition to the skin, which comprises a step of dissolving the fiber aggregate in an aqueous medium to obtain a liquid composition.
The present invention also relates to the use of fiber aggregates for the production of liquid skin external compositions.
The present invention also relates to a method for producing a liquid skin external composition, which comprises a step of dissolving a fiber aggregate in an aqueous medium to obtain a liquid composition.
In addition, the present invention is a liquid skin containing a fiber aggregate formed of a polymer (A) soluble in water and an alcohol or a ketone, a component (B) a poorly water-soluble component, and a component (C) an aqueous medium . Regarding external compositions.
The component (C) preferably contains 60% by mass or more of water.
It is preferable that the droplets containing the component (B) are dispersed in the liquid containing the component (C) as the main component.
The liquid skin external composition is preferably a liquid-liquid dispersion liquid skin external composition.

INDUSTRIAL APPLICABILITY The present invention can provide a composition for external use on the skin, which has excellent applicability to the skin by immobilizing a poorly water-soluble component in a fine particle size and an amorphous state.

It is an optical microscope image which shows that the composition for external use of the present invention is in the form of a liquid-liquid dispersion liquid (Test Example 3). It is an optical microscope image which shows that the composition for external use of the present invention is in the form of a liquid-liquid dispersion liquid (Test Example 5). It is an optical microscope image of Test Example 1. It is an optical microscope image of Test Example 2.

The present inventor has made various studies to allow a poorly water-soluble component to be stably present in a composition in a state of a small particle size without using a surfactant, and to apply it directly to the skin in a liquid state. When a fiber aggregate such as a nanofiber deposit or a crushed product thereof was prepared by electrospinning using a polymer and a poorly water-soluble component soluble in water and alcohol or a ketone, it was difficult to obtain a fiber aggregate in the obtained fiber aggregate. It was found that the water-soluble component was immobilized in an amorphous state. Next, when the fiber aggregate and the aqueous medium were mixed, a liquid-liquid dispersed liquid skin external composition in which droplets containing a poorly water-soluble component were dispersed in a liquid containing the aqueous medium as a main component was obtained. I found that.

In the present invention, since the poorly water-soluble component can be fixed in the fiber structure in an amorphous state, it is in an amorphous state for a long time as compared with the case where the amorphous state is contained in the liquid. Can be maintained. In addition, the fiber aggregate form is excellent in portability and the amount used is easy to understand.
Since the poorly water-soluble component in the fiber structure is in an amorphous state, the solubility when mixed with an aqueous medium can be improved, and a supersaturated state can be easily obtained. That is, it is possible to increase the dissolution concentration of the poorly water-soluble component dissolved in the aqueous medium. The liquid-liquid dispersion liquid external skin composition obtained here is efficient by allowing the poorly water-soluble component to come into direct contact with the skin, that is, the agent having a low water solubility is applied to the skin at a higher concentration. Can be made to.

The fiber aggregate of the present invention specifically means "nanofiber deposit or crushed product thereof".
The fiber aggregate of the present invention contains a component (a) a polymer soluble in water and an alcohol or a ketone, and a component (b) a poorly water-soluble component.
"Water and alcohol or ketone" means "water and alcohol" or "water and ketone".
The nanofiber deposits or crushed deposits thereof include not only the deposits themselves including non-woven fabrics formed of nanofibers, but also compressed or beaten deposits, cut deposits, or crushed deposits. Includes processed products such as non-woven fabric.

The fiber aggregate of the present invention, for example, a nanofiber deposit, can be produced by electrospinning a solution of a component (a) and a component (b) in a solvent containing an alcohol or a ketone. Further, the crushed nanofiber deposit can be produced by crushing the obtained nanofiber deposit.

The component (a) is a polymer that is soluble in water and soluble in alcohol or ketone, and among these, a polymer having a fiber-forming ability is preferable.
The water-soluble polymer is 0. of the polymer soaked in 10 g of deionized water after weighing 1 g of the polymer in an environment of 1 atm and 23 ° C. A polymer having the property of dissolving 5 g or more in water. The alcohol-soluble polymer is 0. of the polymer soaked in 10 g of ethanol after weighing 1 g of the polymer in an environment of 1 atm and 23 ° C. and after 24 hours have passed. A substance having the property of dissolving 5 g or more in ethanol. The polymer soluble in ketone is 0. of the polymer soaked in 10 g of acetone after weighing 1 g of the polymer in an environment of 1 atm and 23 ° C. and after 24 hours have passed. A polymer having a property of dissolving 5 g or more in acetone. Here, "dissolving" means that when a polymer is mixed with water, alcohol or a ketone, the polymer is dispersed in water, alcohol or ketone at 20 ° C., and the dispersed state is visually uniform. It preferably means that it is in a transparent or translucent state visually.

Examples of the component (a) include pullulan, hyaluronic acid, chondroitin sulfate, poly-γ-glutamic acid, modified corn starch, β-glucan, glucooligosaccharide, heparin, mucopolysaccharide such as keratosulfate, cellulose, pectin, xylan, and lignin. Natural highs such as glucomannan, galacturonic acid, psyllium seed gum, tamarind seed gum, arabic gum, tragant gum, soybean water-soluble polysaccharide, alginic acid, carrageenan, laminalan, agarose, fucoidan, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, etc. Molecules: Partially saponified polyvinyl alcohol (when not used in combination with a cross-linking agent), low saponified polyvinyl alcohol, polyvinylpyrrolidone, methacrylic acid copolymer, polyethylene oxide, synthetic polymers such as sodium polyacrylate and the like. These water- and alcohol-soluble polymers can be used alone or in combination of two or more. Among these polymers, one or more synthetic polymers selected from partially saponified polyvinyl alcohol, low saponified polyvinyl alcohol, polyvinylpyrrolidone, and methacrylic acid copolymer from the viewpoint of easy production of nanofiber deposits. It is preferable to use one or more selected from polyvinylpyrrolidone and methacrylic acid copolymers.

The content of the component (a) in the fiber aggregate (specifically, the nanofiber deposit or its crushed product (sometimes simply referred to as “nanofiber”)) is the formability of the nanofiber deposit by electrospinning. From the viewpoint of forming the poorly water-soluble component in the fiber aggregate as an amorphous body of fine particles, and from the viewpoint of dispersing the poorly water-soluble component in the form of droplets in the dispersion medium when mixed with the fiber aggregate. , 50% by mass or more and 98% by mass or less is preferable.
The content of the component (a) in the fiber aggregate is preferably 55% by mass or more from the viewpoint of the formability of nanofiber deposits by electrospinning and the formability of fine particle amorphous body of the poorly water-soluble component. 60% by mass or more is more preferable, and 65% by mass or more is further preferable.
Further, the content of the component (a) in the fiber aggregate is preferably 96% by mass or less, more preferably 90% by mass or less, from the viewpoint of forming a fine particle amorphous body of the poorly water-soluble component.

The component (b) may be a component that is sparingly soluble in water and acts on the skin or humans, and its function is not limited in any way.
The poorly water-soluble means that 1 g of the compound is weighed in an environment of 1 atm and 23 ° C, then immersed in 10 g of deionized water, and after 24 hours, the dissolved amount of the immersed compound is 0.5 g or less. It means having a certain property.
From the viewpoint of improving the effect of stably dispersing the poorly water-soluble component in an aqueous medium such as water, the above-mentioned dissolution amount is preferably 0.0001 g or more, and more preferably 0.001 g or more.
Further, the component (b) is preferably a component having a melting point of 20 ° C. or higher, preferably having a melting point of 20 ° C. or higher, from the viewpoint of the effect of dispersing the component which is sparingly soluble in water and which is normally difficult to precipitate and disperse in an aqueous medium . A component having a temperature of 40 ° C. or higher can be more preferably used.

The analysis of the component (a) and the component (b) contained in the fiber aggregate is performed as follows.
First, the fiber aggregate is dissolved in water. Then, the components that are poorly water-soluble in water are separated by filtration. By drying the filtered liquid component, a component that is a polymer soluble in water is extracted.
Each component obtained above is subjected to various analyzes such as NMR (nuclear magnetic resonance) analysis and IR (infrared spectroscopy) analysis, and the molecular skeleton is based on the position of each signal and spectrum obtained by these analyzes. The structure and the functional group structure at the end of the molecular structure are identified. This identifies the type of component contained.
When multiple compounds are contained in each component, after identifying the structure of the molecular skeleton and the functional group structure at the end of the molecular structure based on the position of each signal and spectrum obtained by the above analysis, the types of components contained are determined. At the same time as identifying, the amount of each component contained can be calculated from the intensity of the measured value indicating the molecular structure corresponding to each component.
The poorly water-soluble compound obtained above can be subjected to DSC analysis, and its melting point can be measured from the melting peak temperature obtained by this analysis.

Such components (b) include polyphenol compounds, amphoteric lipids such as ceramides, fat-soluble vitamins, phytosterols, hexylresolsinol, glycyrrhetinic acid or its derivatives, salicylic acid or its derivatives, steroids or its derivatives, monoterpenes or their derivatives. Examples thereof include derivatives, ubiquinone or derivatives thereof, and among these, polyphenol compounds, ceramides, fat-soluble vitamins, phytosterols, glycyrrhetinic acid or derivatives thereof, steroids or derivatives thereof, monoterpenes or derivatives thereof improve the effects of the present invention. It is preferable from. The function of the component (b) is not limited, but for example, an antibacterial component, a bactericidal component, a beauty component such as an antioxidant component, a whitening component, and an anti-wrinkle component, a hair growth component, a pest and moth repellent component, a fragrance, an essential oil, and a parent medium. Examples include sex lipids, odor control components, skin cooling components and the like.

Examples of the polyphenol as the component (b) include flavonoid compounds as the polyphenol compound, and examples of the flavonoid compound include flavones, isoflavones, coumarins, chromones, dicarbols, chromanones, chromanols, and isomers thereof (for example, cis). / Trans isomers), derivatives, elagic acids, and one or more (mixtures) selected from these. Suitable flavones and isoflavones include unsubstituted flavones, unsubstituted isoflavones, dizeins (7,4'-dihydroxyisoflavones), genistein (5,7,4'-trihydroxyisoflavones), equol (7,4'-isoflavone diols). ), Apigenin (4', 5,7-trihydroxyflavone), quercetin (2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-4H-chromen-4-one), 5,7 -Dihydroxy-4'-methoxyisoflavone, 7,2'-dihydroxyflavone, 3', 4'-dihydroxynaphthoflavone, 7,8-benzoflavone, 4'-hydroxyflavone, 5,6-benzoflavone, soy isoflavone ( For example, isoflavones extracted from soybeans), and such mixtures of other plant, fungal, or bacterial sources (eg, purple foxtail), and mixtures thereof.

Other suitable flavonoids include hesperidin, hesperidin and mixtures thereof. Other polyphenol compounds include tetrahydrocurcuminoids. Tetrahydrocurcuminoids include tetrahydrocurcumin (INCI name tetrahydrodiferloylmethane), tetrahydrodemethoxycurcumin (INCI name tetrahydrodemethoxydiferloylmethane), and tetrahydrobismethoxycurcumin (INCI name tetrahydrobisdemethoxydiferloylmethane). Can be mentioned.
Chromone and chromone derivatives have a linear or branched alkyl group having 1 to 15 carbon atoms at the 2-position of chromone, that is, 4H-1-benzopyran-4-one, and a hydrogen atom and a hydroxy group at the 7-position. Alternatively, a compound having an alkoxy group is preferable.
Examples of such chromone derivatives include 2-butylchromone, 2-pentylchromone, 2-heptylchromone, 2-nonylchromone, 2-hexadecylchromone, 2- (1-ethylpentyl) chromone, 2-butyl-7. -Methoxychromone, 2-pentyl-7-methoxychromone, 2-heptyl-7-methoxychromone, 2-nonyl-7-methoxychromone, 2-pentadecyl-7-methoxychromone, 2- (1-ethylpentyl) -7 -Methoxychromone, 7-hydroxy-2-methylchromone, 7-hydroxy-2-butylchromone, 7-hydroxy-2-pentylchromone, 7-hydroxy-2-heptylchromone, 7-hydroxy-2-nonylchromone, 7- Examples thereof include hydroxy-2-pentadesilcromon, 7-hydroxy-2- (1-ethylpentyl) chromone and the like.

Examples of the amphoteric lipid as the component (b) include higher fatty acids such as myristic acid and stearic acid; higher alcohols such as cetanol, stearyl alcohol and behenyl alcohol; sphingosine such as sphingosine; and ceramides. Examples of ceramides include Robson K. ceramides. J. et al. , J. Lipid Res. , 35, 2060 (1994) and Wertz P. et al. W. et al. , J. Lipid Res. , 24,759 (1983) and the like, ceramides having various structures referred to as type 1 to type 6, and ceramide-like compounds described in JP-A-62-228048 (eg, N- (2-hydroxy-3). -Hexadecyloxypropyl) -N-2-hydroxyethylhexadecanamid) and the like are included. Ceramides have either sphingosine or phytosphingosine as a skeleton, and fatty acids, α-hydroxy acids or ω-hydroxy acids are bound by amide bonds. It includes several compounds with different fatty acids carbon number and degree of unsaturation. Both have high crystallinity, a high melting point, and are solid at room temperature (20 ° C.). Of these, (2S, 3R) -2-octadecanoylaminooctadecane-1,3-diol (hereinafter referred to as ceramide 2) and N-2-hydroxystearoyl are preferable because of their availability in the market. Phytosphingosine (hereinafter referred to as ceramide 6). These are obtained by extraction or synthesis from animals and plants, but are not limited to these. Specifically, N-stearoyl phytosphingosine (manufactured by Nikko Chemicals Co., Ltd.), ceramide HO3 (manufactured by Croder Japan), ceramide III, ceramide IIIB, ceramide IIIA, ceramide IV, phytoceramide I (above, Degusa), ceramide. II (Cederma Co., Ltd.), Ceramide TIC-001 (manufactured by Takasago International Corporation), and the like can be mentioned. Since ceramide is a constituent of stratum corneum intercellular lipids, it is known to be effective from the viewpoint of skin moisturizing property and barrier function.

Examples of the fat-soluble vitamin as the component (b) include vitamin A such as retinol, α-carotene, β-carotene, γ-carotene and cryptoxanthin, various vitamin Ds, tocopherols and derivatives thereof. Examples of tocopherol and its derivatives include tocopherol succinate, nicotinic acids; α-tocopherol, dl-α-tocopherol acetate, tocopherol nicotinate, vitamin Es such as natural vitamin E, and the like.

The phytosterol as the component (b) may be synthetic or naturally derived and can be used as a pure compound or a mixture of compounds (eg, an extract from a natural resource). Phytosterols are commonly found in the unsaponified fractions of vegetable oils and fats and are available as free sterols, acetylated derivatives, sterol esters, ethoxylated or glycoside derivatives. Typical phytosterols include β-sitosterol, campesterol, brassicasterol, δ-5-ave na sterol, rupenol, α-spinasterol and stigmasterol.

Hexylresorcinol as a component (b) is known to have properties as a bactericide and an insect repellent, and is also known as a therapeutic agent for skin infections and an antioxidant. Examples of the glycyrrhetinic acid or a derivative thereof as the component (b) include β-glycyrrhetinic acid, glycerin glycyrrhetinate, stearyl glycyrrhetinate and the like. These are known to have effects such as anti-inflammatory agents. Examples of salicylic acid or a derivative thereof as the component (b) include salicylic acid, methyl salicylate, salicylamide and the like. These are known to have anti-inflammatory, antipyretic, and analgesic effects.

The steroid as the component (b) refers to a hormone having a steroid skeleton, and the compounded drug is generally referred to as a steroid preparation. Examples of steroids include estrogen, progesterone, testosterone, dehydroepiandrosterone, prednisolone, prednisone, progesterone, pregnenolone and the like.

Examples of the monoterpene as the component (b) include linalool, menthol, camphor and the like, and examples of the monoterpene derivative include carvacrol, thymol, isopropylmethylphenol and the like. For example, thymol is known to have bactericidal and antibacterial properties, isopropylmethylphenol is known to have bactericidal performance, camphor is known to promote blood circulation and anti-inflammatory analgesia, and menthol is known to have cooling sensation, analgesia, and anti- inflammatory analgesia enhancement. The present invention can be suitably used for thymol, camphor and menthol which are solid at 20 ° C.

Examples of the ubiquinone or a derivative thereof as the component (b) include oxidized ubiquinone, ubiquinol which is a reduced ubiquinone, and examples thereof include coenzyme Q, coenzyme Q10, CoQ10, and ubidecalenone .

Examples of the component (b) used as an antibacterial component or a bactericidal component include a phenolic antibacterial agent. Examples of the phenol-based antibacterial agent include chlorophenol-based antibacterial agents such as triclosan, chlortimol, carbachlor, chlorophen, dichlorophen, hexachlorophene, chloroxylenol and chlorocresol; O-phenylphenol, isopropylmethylphenol, thymol and the like. Can be mentioned. Of these, isopropylmethylphenol and thymol are more preferable.

Examples of the hair-growth component include flavanonol derivatives such as trans-3,4'-dimethyl-3-hydroxyflabanone; nicotinic acids such as benzyl nicotinate, tocopherol nicotinate, β-butoxyethyl nicotinate; α-tocopherol, dl acetate. -Α-Vitamin Es such as tocopherol, tocopherol nicotinate, and natural vitamin E; examples thereof include minoxidil, bimatoprost, tafluprost, nonyl acid vanillylamide, and otogiri grass extract.

The content of the component (b) in the fiber aggregate is determined from the viewpoint of the formability of nanofiber deposits by electrospinning, the viewpoint of the formability of fine particles of poorly water-soluble components in the nanofiber deposits, and the formability of amorphous bodies. When the fiber aggregate is mixed with an aqueous medium, the content is preferably 2% by mass or more and 40% by mass or less from the viewpoint of dispersing the poorly water-soluble component in a liquid state in the aqueous medium.
In addition, the content of the component (b) in the fiber aggregate improves the formability of the amorphous body of the fine particles of the nanofiber deposit by electrospinning, the dispersibility of the poorly water-soluble component, and has a higher concentration. From the viewpoint that the poorly water-soluble component can be applied to the object, 3% by mass or more is preferable, 5% by mass or more is more preferable, and 8% by mass or more is further preferable.
Further, the content of the component (b) in the fiber aggregate is the formability of the amorphous body of the fine particles of the poorly water-soluble component and the amorphous of the poorly water-soluble component even if the fiber aggregate is stored for a long time. From the viewpoint of maintaining the state of 40% by mass or less, 35% by mass or less is more preferable, and 30% by mass or less is further preferable. The content of the component (b) in the fiber aggregate is particularly preferably 20% by mass or less from the viewpoint of stability after mixing with an aqueous medium.

The mass ratio of the component (a) to the component (b) in the fiber aggregate (mass of the component (a) / mass of the component (b)) is amorphous of the fine particles of the poorly water-soluble component in the fiber aggregate. From the viewpoint of body formation, from the viewpoint of dispersing the poorly water-soluble component in a liquid state in the dispersion medium when the fiber aggregate is mixed with an aqueous medium, the amorphous state of the poorly water-soluble component is maintained in the fiber aggregate. From the viewpoint of the above, 2 or more is preferable, and 2 or more and 49 or less are more preferable.
Further, from the viewpoint of facilitating the maintenance of the poorly water-soluble functional component in the fiber aggregate in an amorphous state, 2 or more is preferable, 3 or more is more preferable, and 4 or more is further preferable.
Further, 19 or less is preferable, and 11 or less is more preferable, from the viewpoint that the poorly water-soluble functional component can be applied to the skin at a higher concentration.

The fiber aggregate can be produced by electrospinning a solution in which the component (a) and the component (b) are dissolved. As the solvent of the solution containing the component (a) and the component (b) used for electrospinning, one or more volatile solvents selected from alcohols and ketones are preferable. The solvent may contain water.
In the electrospinning method, the component (a) and the component (b) are sufficiently charged with the solution containing the component (a) and the component (b) placed in the electric field, and then the substrate or the base material is charged from the tip of the nozzle. It is ejected onto human skin. When the solution containing the component (a) and the component (b) evaporates, the charge density of the solution becomes excessive, and the solution containing the component (a) and the component (b) further becomes finer due to Coulomb repulsion. It evaporates and finally forms a dry fiber aggregate.

As the alcohol as the solvent, for example, a monovalent chain aliphatic alcohol, a monovalent ring-type aliphatic alcohol, and a monovalent aromatic alcohol are preferably used. The monovalent chain fatty alcohol is a linear or branched alcohol having 1 to 6 carbon atoms, and the monohydric ring fatty alcohol is a ring fatty alcohol having 4 to 6 carbon atoms, monohydric. Examples of the aromatic alcohol in the above include benzyl alcohol and phenylethyl alcohol. Specific examples thereof include methanol, ethanol, isopropyl alcohol, n-propyl alcohol, n-butyl alcohol, 2-butyl alcohol, isobutyl alcohol, 2-methyl-2-propyl alcohol, n-pentanol, and 2-pentanol. , 3-Pentanol, 2-Methyl-1-butyl alcohol, 2-Methyl-2-butyl alcohol, 3-Methyl-1-butyl alcohol, 3-Methyl-2-butyl alcohol, Neopentyl alcohol, n-Hexanol, 2-hexanol, 3-hexanol, 2-methyl-1-pentanol, 3-methyl-1-pentanol, 4-methyl-1-pentanol, 2-methyl-2-pentanol, 3-methyl-2- Pentanol, 4-methyl-2-pentanol, 2-methyl-3-pentanol, 3-methyl-3-pentanol, 2,2-dimethyl-1-butanol, 2,3-dimethyl-1-butanol, 3,3-dimethyl-1-butanol, 2,3-dimethyl-2-butanol, 3,3-dimethyl-2-butanol, 2-ethyl-1-butanol, cyclobutanol, cyclopentanol, cyclohexanol, benzyl alcohol , Phenylethyl alcohol and the like. These alcohols can be used alone or in combination of two or more selected from them.
Examples of the ketone as a solvent include acetone, diethyl ketone, methyl propyl ketone, methyl amyl ketone, methyl ethyl ketone, methyl isobutyl ketone, methyl-n-hexyl ketone, methyl-n-propyl ketone, diisopropyl ketone, diisobutyl ketone, hexafluoroacetone and the like. , And one or a combination of two or more selected from these can be used.

As the solvent, one or two or more selected from alcohols and ketones are preferable, and one or two selected from aliphatic alcohols having 1 to 6 carbon atoms and aliphatic ketones having 1 to 6 carbon atoms are more preferable. .. It is more preferably one or more selected from ethanol, isopropyl alcohol, n-butyl alcohol and acetone, still more preferably one or more selected from ethanol, isopropyl alcohol and acetone, and even more preferably. Is ethanol.

In a more preferred form, the content of the solvent (preferably alcohol or ketone) in the solution containing the component (a) and the component (b) is 50% by mass or more 94 from the viewpoint of the formability of the target fiber aggregate. It is preferably 50% by mass or less, more preferably 50% by mass or more and 92% by mass or less, and further preferably 50% by mass or more and 90% by mass or less.
The solvent may contain water, and the content of water should be 5% by mass or less in the solvent from the viewpoint of the stability of the poorly water-soluble component in the fiber aggregate or the composition. It is preferably 1% by mass or less, and more preferably 0.1% by mass or more from the viewpoint of electrospinnability.
The content of the component (a) is preferably 5% by mass or more and 40% by mass or less, more preferably 6% by mass or more and 35% by mass or less, and 8% by mass in the solution from the viewpoint of the formability of the target fiber aggregate. % Or more and 30% by mass or less are more preferable.
The content of the component (b) is preferably 0.05% by mass or more and 20% by mass or less, and more preferably 0.5% by mass or more and 15% by mass or less in the solution from the viewpoint of the formability of the target fiber aggregate. It is preferable, 1% by mass or more and 10% by mass or less is more preferable.
Further, the total content of the component (a) and the component (b) in the solution may be 5.05% by mass or more and 50% by mass or less from the viewpoint of efficiently and stably forming the fiber aggregate. It is more preferably 6.05% by mass or more and 45% by mass or less, further preferably 6.05% by mass or more and 40% by mass or less, and further preferably 9% by mass or more and 35% by mass or less. It is preferably 9% by mass or more and 32% by mass or less.

Further, in the solution, a plasticizer, a feel improver, a conductivity control agent, a coloring pigment, an extender pigment, a dye, and a fragrance other than the component (a) and the component (b) are added to the extent that the effect of the present invention is not impaired. , Repellents, Antioxidants, Stabilizers, Preservatives, Additives such as Various Vitamin.
The plasticizer can impart flexibility to the fiber aggregate formed by electrospinning. As such a plasticizer, an oil agent liquid at 20 ° C. is preferable.
In addition, the feel-improving agent, when used in combination with a plasticizer, imparts flexibility to the fiber aggregate formed by electrospinning and improves the feel (smoothness, oiliness, squeaky feeling, stickiness, etc.).
The plasticizer and the feel-improving agent are not particularly limited as long as they can be generally used in the field of cosmetics, and for example, polyols, polyoxyalkylene glycols, polyoxyalkylene alkyl ethers, ester oils, silicone oils, and hydrocarbon oils. , Liquid fats and oils, solid fats and oils, higher alcohols, nonionic surfactants and the like can be used alone or in combination of two or more.
The conductivity control agent is preferably an alkali metal salt or an ammonium salt, more preferably an ionic surfactant, and further preferably a cationic surfactant and an anionic surfactant from the viewpoint of improving conductivity. One or more selected from the agents.
The content of the surfactant in the solution used for electrospinning and the content of the surfactant in the component (a) are poorly water-soluble in the fiber aggregate from the viewpoint of improving the applicability to the skin. It is preferably 0% by mass or more and 50% by mass or less, and more preferably 25% by mass or less with respect to the amount of the component.
These additives and surfactant components in the solution used for electrospinning can be identified by the following means. First, the fiber aggregate to be measured is dissolved in various solvents, and the solution is subjected to pyrolysis gas chromatograph (GC-MS) analysis. The compound is identified from the mass spectrum obtained here, and the content is calculated.

The viscosity range of the solution containing the component (a) and the component (b) for electrospinning is preferably 2 mPa · s or more and 3000 mPa · s or less, and more preferably 5 mPa · s or more and 2000 mPa · s or less. It is more preferably 10 mPa · s or more and 1500 mPa · s or less, further preferably 30 mPa · s or more and 1000 mPa · s or less, further preferably 50 mPa · s or more and 800 mPa · s or less, and 80 mPa · s. It is even more preferable that the content is 500 mPa · s or less.
The viscosity of the solution is measured at 25 ° C. using a B-type viscometer. As the B-type viscometer, a B-type viscometer (TVB-10M) manufactured by Toki Sangyo Co., Ltd. can be used. In that case, the measurement condition is that the measurement temperature is 25 ° C. At this time, the measured temperature is the temperature of the solution. The type of rotor and the number of rotations of the rotor are selected according to the specifications of the measuring equipment to be used according to the viscosity of the solution. When the TVB-10M is used, if the viscosity of the film-forming composition is 2500 mPa · s or more, the viscosity is 6 rpm using an M2 rotor, and if the viscosity is 1000 mPa · s or more and less than 2500 mPa · s, the viscosity is 12 rpm using an M2 rotor, 500 mPa · s. More than 1000 mPa · s can be measured at 30 rpm using an M2 rotor, 100 mPa · s or more and less than 500 mPa · s can be measured at 60 rpm using an M2 rotor, and less than 100 mPa · s can be measured at 60 rpm using an M1 rotor. Further, the specification manual of the TVB-10M also describes measurement conditions other than the above measurement conditions, and the viscosity can be measured under other measurement conditions depending on the viscosity of the solution.

In order to produce nanofiber deposits by electrospinning using the solution, for example, an electrospinning device having the structure shown in FIG. 2 of Patent Document 1 is used to apply the solution on a substrate or human skin. It may be electrospun.
Crushed nanofiber deposits can be obtained by crushing the resulting deposits.

The resulting fiber aggregate contains the component (a) and the component (b) because the solvent evaporates by electrospinning.
In the obtained fiber aggregate, the component (a) is preferably 50% by mass or more and 98% by mass or less with respect to the entire fiber aggregate, and the component (b) is 2% by mass or more with respect to the entire fiber aggregate. Contains 40% by mass or less.

The average fiber diameter of the fiber aggregate increases the strength of the nanofibers and makes it easier to maintain the fiber morphology, so that the poorly water-soluble functional components dispersed in the nanofibers are less likely to be deformed and become amorphous. From the viewpoint of facilitating maintenance and suppressing an increase in particle size due to aggregation, 20 nm or more is preferable, 30 nm or more is more preferable, and 50 nm or more is further preferable.
Further, from the viewpoint that the fiber aggregate is easily dissolved quickly and the poorly water-soluble component is easily dispersed in the dispersion medium in the form of droplets, 5000 nm or less is preferable, 4000 nm or less is more preferable, and 3000 nm or less is further preferable.
The fiber diameter is, in principle, the diameter of the cross section of the fiber. Here, when the cross section of the fiber is a circle, it is the diameter, but when the cross section is an ellipse, it is the major axis. The fiber diameter is arbitrary, for example, a fiber obtained by magnifying the fiber 2000 times or 5000 times by observation with a scanning electron microscope and removing defects (for example, a lump of the fiber, an intersection of the fibers) from the two-dimensional image thereof. It can be measured by selecting 100 fibers, drawing a line orthogonal to the longitudinal direction of the fiber, and directly reading the fiber diameter. For the average fiber diameter, the arithmetic mean of these measured values is obtained, and this is taken as the average fiber diameter.
The CV value of the average fiber diameter of the nanofiber deposit is preferably 10 to 100%, more preferably 12 to 95%, and 15 to 15 to 100% from the viewpoint of forming a network in the deposit. It is more preferably 90%.

Further, the fiber diameter of the crushed product of the nanofiber deposit is the same as that of the fiber aggregate.
The average fiber length of the crushed product is preferably 20 μm or more and 300 μm or less, more preferably 30 μm or more and 250 μm or less, and further preferably 40 μm or more and 200 μm or less. The fiber length is observed at a magnification of 250 to 750 times depending on the length of the fiber, for example, by observation with a scanning electron microscope, and defects (for example, lumps of fibers, intersections of fibers) are observed from the two-dimensional image. It can be measured by arbitrarily selecting 100 fibers excluding the above fiber, drawing a line in the longitudinal direction of the fiber, and directly reading the fiber length. The average fiber length was defined as the average fiber length by calculating the arithmetic mean of these measured values.
Further, the CV value of the average fiber length of the crushed nanofiber deposit is from the viewpoint of forming a network when the crushed nanofiber deposit is applied on the skin, or from the viewpoint of applicability to the skin. Therefore, it is preferably 40 to 100%, more preferably 42 to 95%, and even more preferably 45 to 90%. Whether or not the fibers form a network in the nanofiber deposit can be confirmed by a scanning electron microscope or the like. Further, the network is a state in which the fibers dispersed in the nanofiber deposit have two or more intersections with each other so as to have a gap between the fibers.

In the present invention, whether or not the poorly water-soluble component in the fiber aggregate exists in an amorphous state can be confirmed by the presence or absence of a detection peak obtained by X-ray diffraction (XRD) analysis. Specifically, when the poorly water-soluble component exists as a crystal, X-ray diffraction analysis confirms a detection peak derived from the crystal structure of the poorly water-soluble component. On the other hand, when the poorly water-soluble component exists in an amorphous state, no peak derived from the crystal structure is confirmed. Further, it can be confirmed by measuring the relaxation time by solid-state NMR that the poorly water-soluble component exists in the form of fine particles.
Specifically, in the solid-state NMR measurement, the longitudinal relaxation (spin-lattice relaxation) time T1 and the longitudinal relaxation time T1ρ in the rotation system are measured, and these relaxation times (T1, T1ρ) and the spin diffusion coefficient D of the organic solid are calculated. The effective spin diffusion distance L is obtained from the following equation, and the spin effective diffusion distance L obtained from this is regarded as the distance information between organic substances, that is, the particle size.
L = (6 × D × t) ^ (1/2)
As a measurement condition of solid-state NMR, the fiber aggregate is cut to about 5 mm and filled in a φ7 mm sample tube. Then, the Bruker DSX300WB, 7 mm MAS probe is used to measure the ¹³ C-CPMAS spectrum. ¹³ The signal positions of the polymer forming the fiber and the poorly water-soluble functional component are identified from the C-CPMAS spectrum, and the relaxation times T1 and T1ρ are measured at these signal positions. At this time, when the polymer and the poorly water-soluble functional component T1 or T1ρ are almost the same, it is assumed that the relaxation time of the polymer and the poorly water-soluble functional component are the same by spin diffusion, and the calculation is made from the above formula. It is considered that the particle size is smaller than the L value to be obtained, and if the polymer and T1 or T1ρ of the poorly water-soluble functional component do not match, it is considered that the particle size is larger than the L value calculated from the above formula. The particle size is identified from these calculation results.
In the present invention, it is considered that the poorly water-soluble component is dispersed as fine particles in the fiber aggregate, so that it can be stored for a long time in an amorphous state.
The smaller the particle size of the poorly water-soluble component in the amorphous state, the more difficult it is to crystallize with time. Therefore, the particle size of the component (b) contained in the fiber is preferably small. Specifically, it is preferably 10 nm or less, more preferably 5 nm or less, and even more preferably 3 nm or less.
Moreover, it is realistic that it is 0.1 nm or more.

In the present invention, by mixing the fiber aggregate containing the component (a) and the component (b) with an aqueous medium, the component (A) is formed of a polymer soluble in water and an alcohol or a ketone. A liquid skin external composition containing a fiber aggregate, a component (B) a poorly water-soluble component, and (C) an aqueous medium can be obtained.
In the composition, the droplets containing the component (B) are dispersed in a liquid containing the component (C) as a main component in an amorphous state, and the component (A) is dissolved in the component (C). , A liquid-liquid dispersion liquid skin external composition in which the component (B) is dissolved in a supersaturated state can be obtained. In particular, the supersaturated state in the best state can be obtained immediately after the fiber aggregate is mixed with the aqueous medium.
Here, the supersaturated state is a case where the component (B) is dissolved in the component (C) in an environment of 20 ° C. and 50% RH , and the concentration of the component (B) after a sufficient time has passed is defined as the solubility. In addition, it means that the component (B) is dissolved in the component (C) more than the solubility.
To confirm that the component (B) is in a supersaturated state, first, in an environment of 20 ° C. and 50% RH , the fiber aggregate containing the above-mentioned component (a) and the component (b) and an aqueous medium are mixed. After mixing, a filtrate is obtained by filtering using a membrane filter having an opening of 0.2 μm. After that, the obtained filtrate is allowed to stand in the same environment for 24 hours or more. When a precipitate of the component (B) is generated in the filtrate that has been allowed to stand for 24 hours, it can be confirmed that the component (B) is dissolved in the component (C) in a supersaturated state.

Amorphous droplets containing the component (B) are dispersed in a liquid containing the component (C) as a main component, the component (A) is dissolved in the component (C), and the component (B) is formed. In order to obtain a liquid-liquid dispersion liquid skin external composition dissolved in a hypersaturated state, an aqueous solution containing 60% by mass or more of water containing the fiber aggregate containing the above-mentioned components (a) and (b). It is preferable to mix with the medium.
Here, examples of the fiber aggregate containing the component (a) and the component (b) include the above-mentioned fiber aggregate, and the preferable contents of the component (a) and the component (b) are also as described above. be.
The fact that the liquid-skin external composition obtained by the present invention forms the above-mentioned liquid-liquid dispersion liquid means that a fiber aggregate is placed on a slide glass, a cover glass is placed on the slide glass, and the slide glass is formed. It can be confirmed by applying an aqueous medium containing 60% by mass or more of water through the gap of the cover glass and observing the liquid in which the fiber aggregate is dissolved with an optical microscope.
The liquid-liquid dispersion liquid-forming liquid droplet component can be subjected to micro-FT-IR analysis to determine the molecular structure from the IR spectrum obtained from the droplet surface and identify the composition contained therein. can.
To check whether the droplets of the component (B) in the liquid skin external composition obtained by the present invention are in an amorphous state, place a fiber aggregate on a slide glass, place a cover glass on the slide glass, and slide. Apply an aqueous medium containing 60% by mass or more of water through the gap between the glass and the cover glass, observe the liquid in which the fiber aggregates are dissolved with a polarizing microscope, and confirm the change in color and brightness due to the crystal structure. It can be confirmed by.
Further, in the liquid skin external composition of the present invention, the liquid means that it is liquid at 20 ° C.

Therefore, the present invention provides a liquid skin external composition manufacturing kit comprising a fiber aggregate containing the component (a) and the component (b) and an aqueous medium as the component (C).

The content of water in the component (C) is preferably 60% by mass or more and 100% by mass or less, and 70% by mass or more and 100% by mass or less, from the viewpoint of forming the liquid-liquid dispersion liquid skin external composition. It is more preferably 80% by mass or more and 100% by mass or less.
The content of water in the component (C) can be measured by using the Karl Fischer method (JIS K 0068).

Further, the component (C) may contain an alcohol having 3 or more carbon atoms, which is liquid at 20 ° C. when mixed with water at the above ratio. As such an alcohol, an aliphatic alcohol having 3 to 6 carbon atoms and a polyhydric alcohol are preferable. More preferably, isopropyl alcohol and alkylene glycols such as n-butyl alcohol, ethylene glycol, propylene glycol (PG), 1,3-propanediol, 1,3-butanediol; diethylene glycol, dipropylene glycol (DPG), weight. Polyalkylene glycols such as polyethylene glycol and polypropylene glycol having an average molecular weight of 2000 or less; one or more selected from glycerins such as glycerin, diglycerin and triglycerin, and more preferably isopropyl alcohol and dipropylene. One or more selected from glycol (DPG), propylene glycol (PG) and glycerin, and more preferably dipropylene glycol (DPG).
The total content of alcohols and ketones having 2 or less carbon atoms in the component (C) is the stability of the poorly water-soluble component during or after the formation of the liquid skin external composition after the application of the component (C), and the skin. From the viewpoint of applicability to, 40% by mass or less is preferable, 30% by mass or less is more preferable, and 20% by mass or less is further preferable.
From the same viewpoint, the content of the alcohol or ketone used in the electrospinning solution forming the fiber aggregate is preferably 30% by mass or less, and more preferably 20% by mass or less. It is more preferably 10% by mass or less.
The content of the surfactant in the component (C) is preferably 0% by mass or more and 5% by mass or less from the viewpoint of applicability of the poorly water-soluble component after formation of the liquid skin external composition to the skin. , 0% by mass or more and 3% by mass or less is more preferable, and 0% by mass or more and 1% by mass or less is further preferable, and it may be substantially not contained. It is preferable not to contain a surfactant from the viewpoint that an amorphous state and fine droplet-like poorly water-soluble components can be applied to the skin without impairing the barrier function of the skin.
The content of the surfactant in the formed liquid skin external composition is preferably 0% by mass or more and 3% by mass or less, preferably 0% by mass or more 1 from the viewpoint of applicability of the poorly water-soluble component to the skin. It is more preferably 0% by mass or less, and further preferably 0% by mass or more and 0.5% by mass or less.
For the analysis of the component in the component (C), a pyrolysis gas chromatograph (GC-MS) analysis is performed, the compound is identified from the mass spectrum obtained here, and the content is calculated from the detection intensity of the mass spectrum. You can also do it.

Further, the fiber aggregate can be produced on a base material and kept in a sheet-like form. The base material is preferably water-insoluble. In the present invention, the term "water insoluble" in a substrate means that 1 g of the substrate is weighed in an environment of 1 atm and 23 ° C, then immersed in 10 g of deionized water, and after 24 hours, the immersed substrate is 0. A substance having a property of not dissolving more than .5 g, preferably a substance having a property of not dissolving more than 0.8 g. In other words, water insoluble means that 1 g of the substrate is weighed in an environment of 1 atm and 23 ° C, then immersed in 10 g of deionized water, and after 24 hours, less than 0.5 g of the immersed substrate. Has the property of dissolving, preferably less than 0.2 g has the property of dissolving. From this viewpoint, it is preferable that the base material is composed of a water-insoluble polymer compound. The form of the base material is preferably various non-woven fabrics, meshes, and films.
The thickness of the base material is preferably 3 μm or more, more preferably 5 μm or more, and even more preferably 10 μm or more. The thickness of the base material is preferably 1000 μm or less, more preferably 500 μm or less, and even more preferably 450 μm or less. Specifically, the thickness of the base material is preferably 3 μm or more and 1000 μm or less, more preferably 5 μm or more and 500 μm or less, and further preferably 10 μm or more and 450 μm or less. In this case, the kit comprises a sheet-like composition composed of the fiber aggregate and the aqueous medium.
A kit having such a sheet-like composition and the aqueous medium is excellent in portability, the amount used is easy to understand, and the stability of the poorly water-soluble component can be ensured.

The fiber aggregate can be added to the aqueous medium to obtain a liquid composition, and the liquid composition can be applied to the skin. Specifically, 0 minutes or more and 180 minutes or less, preferably 0 minutes or more and 30 minutes or less, more preferably 0 minutes or more and 10 minutes or less, still more preferably 0 minutes or more after the fiber aggregate is added to the aqueous medium. The liquid composition can also be applied to the skin within 5 minutes. More specifically, the mixing of the fiber aggregate and the aqueous medium may be performed in a container immediately before application to the skin, or may be performed on the skin to be applied.
By applying the liquid composition to the skin within this time range, the droplets containing the poorly water-soluble component do not extremely aggregate, and the poorly water-soluble component remains in an amorphous state. Can be applied to the skin.
Further, by applying the aqueous medium to the surface of the skin and applying the fiber aggregate on the surface of the skin, the fiber aggregate may be dissolved in the aqueous medium to form a liquid composition on the skin. Specifically, the fiber aggregate is placed in a sheet-like form and mixed with an aqueous medium is performed on the skin to which the aqueous medium is applied, from the viewpoint of directly applying the droplet containing the poorly water-soluble component to the skin. It is preferable from.

In the liquid composition, the combined ratio of the fiber aggregate to the aqueous medium is the mass (mg) of the fiber aggregate from the viewpoint that the poorly water-soluble component can be easily dissolved in the aqueous medium in a hypersaturated state. ) And the mass (mg) of the aqueous medium (mass of fiber aggregate (mg) / mass of aqueous medium (mg)) is preferably 0.0001 mg / mg or more, more preferably 0.001 mg / mg or more. More preferably, 0.005 mg / mg or more.
From the same viewpoint, the liquid composition contains water in an amount of preferably 6% by mass or more, more preferably 8% by mass or more, still more preferably 10% by mass or more, based on the whole composition.
The liquid composition has a mass (mg) of the fiber aggregate / a mass of the aqueous medium (mg) from the viewpoint that the fiber aggregate can be reliably dissolved in the aqueous medium and droplets of the poorly water-soluble component can be dispersed. ) Is preferably 10 mg / mg or less, more preferably 9 mg / mg or less, still more preferably 8 mg / mg or less.
From the same viewpoint, the liquid composition preferably contains water in an amount of 99.9% by mass or less, more preferably 99% by mass or less, still more preferably 98% by mass or less, based on the whole composition.

When the fiber aggregate and the aqueous medium are mixed in a container, both may be added to the container and then the container may be shaken by hand. When mixing on the skin, both may be placed on the skin and then immediately mixed by fingers.

By the above operation, it is possible to easily form a liquid-liquid dispersion liquid skin external composition in which droplets containing the component (B) are dispersed in a liquid containing the component (C) as a main component. Here, the average particle size of the droplet containing the component (B) is preferably 100 μm or less, more preferably 80 μm or less, still more preferably 50 μm or less, from the viewpoint of ensuring the skin applicability of the component (B).
The average particle size of the droplets in the present invention is preferably the average particle size within 30 seconds after the formation of the liquid skin external composition (after application of the aqueous medium), and is preferably 0.001 μm or more. For the average particle size of the droplets, a fiber aggregate is placed on a slide glass, a cover glass is placed on the slide glass, and an aqueous medium containing 60% by mass or more of water is applied from the gap between the slide glass and the cover glass. Within 30 seconds after application of the aqueous medium, an image is taken by observing with an optical microscope at a magnification of 50 to 1000 times depending on the size of the droplet, and arbitrarily 50 droplets are taken from the two-dimensional image. It can be measured by selecting and drawing a line in the longitudinal direction of the droplet and reading the particle length directly. The average particle length can be calculated as the average particle diameter by obtaining the arithmetic mean of these measured values.

The combination of the component (B) and the component (C) that enables the formation of droplets of the component (B) is the logarithm of the water dissolution concentration S estimated using the commercially available Hansen solubility parameter estimation software HSPiP, log S. It can be judged from. When the solubility of the component (B) in water is log S> -5, it can be confirmed from the observation with an optical microscope that droplets containing the component (B) can be formed even if the component (C) is only water. On the other hand, when the solubility of the component (B) in water is log S ≦ −5, the component (B) is contained by adding a solvent having an affinity for the component (B) to the component (C). It has been confirmed by observation with an optical microscope that droplets can be formed.

When the liquid external composition for skin of the present invention is applied to the skin, the poorly water-soluble component can be applied to the skin in a liquid form, so that the poorly water-soluble component can be brought into direct contact with the skin, which is effective for the skin. A poorly water-soluble component can be applied. It is considered that by directly contacting the poorly water-soluble component with the skin, for example, the permeability to the skin can be improved or the skin can be brought into contact with the skin at a high concentration. Further, in the present invention, direct contact means that a poorly water-soluble component such as emulsified particles does not exist in the micelle or is not encapsulated, and preferably an oil-based component or an oil-based component is preferably placed between the emulsion and the aqueous medium. It is considered that there is almost no surfactant. Further, by using the kit of the present invention, it is excellent in portability, the amount used is easy to understand, and the stability of the poorly water-soluble component can be guaranteed.

With respect to the embodiments described above, the present invention further discloses the following compositions and methods.

<1> A fiber aggregate
Ingredient (a) contains a polymer soluble in water and alcohol or ketone, and ingredient (b) contains a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
A fiber aggregate for producing a liquid skin external composition, which contains the component (b) in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
<2> A fiber aggregate
Ingredient (a) contains a polymer soluble in water and alcohol or ketone, and ingredient (b) contains a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
The component (b) is contained in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
A fiber aggregate having a particle size of the component (b) contained in the fiber of 0.1 nm or more and 10 nm or less.
<3> The fiber aggregate according to <1> or <2>, wherein the component (b) is contained in the fiber in an amorphous state.
<4> A fiber aggregate
Ingredient (a) contains a polymer soluble in water and alcohol or ketone, and ingredient (b) contains a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
The component (b) is contained in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
A fiber aggregate in which the component (b) is contained in the fiber in an amorphous state.
<5> The description according to any one of <2> to <4>, wherein the particle size of the component (b) contained in the fiber is 0.1 nm or more and 5 nm or less, preferably 0.1 nm or more and 3 nm or less. Fiber aggregate.

<6> A kit containing the fiber aggregate according to any one of <1> to <5> and an aqueous medium, preferably the aqueous medium contains 60% by mass or more and 100% by mass or less of water, more preferably. A liquid skin external composition manufacturing kit containing 70% by mass or more and 100% by mass or less.
<7> The kit according to <6>, wherein the average fiber diameter of the fibers in the fiber aggregate is 20 nm or more and 5000 nm or less.
<8> The kit according to <6>, wherein the average fiber diameter of the fibers in the fiber aggregate is 30 nm or more and 4000 nm or less, preferably 50 nm or more and 3000 nm or less.
<9> The component (a) is one or more selected from pullulan, partially saponified polyvinyl alcohol, low saponified polyvinyl alcohol, polyvinylpyrrolidone, and a methacrylic acid copolymer, according to any one of <6> to <8>. The kit described.
<10> The ratio of the fiber aggregate to the aqueous medium (mass of the fiber aggregate (mg) / mass of the aqueous medium (mg)) is 0.0001 mg / mg or more and 10 mg / mg or less <6. The kit described in any of> to <9>.
<11> The ratio of the fiber aggregate to the aqueous medium (mass of the fiber aggregate (mg) / mass of the aqueous medium (mg)) is 0.001 mg / mg or more and 9 mg / mg or less <6. The kit described in any of> to <9>.
<12> The mass ratio of the component (a) to the component (b) in the aggregate (mass of the component (a) / mass of the component (b)) is 2 or more and 49 or less <6>. The kit according to any one of ~ <11>.
<13> The mass ratio of the component (a) to the component (b) in the aggregate (mass of the component (a) / mass of the component (b)) is 3 or more and 19 or less <6>. The kit according to any one of ~ <11>.
<14> The kit according to any one of <6> to <13>, wherein the melting point of the component (b) is 20 ° C. or higher, preferably 40 ° C. or higher.
<15> The component (b) is one or more selected from polyphenol compounds, ceramides, fat-soluble vitamins, phytosterols, glycyrrhetinic acid or its derivatives, steroids or its derivatives, and monoterpenes or their derivatives. The kit according to any one of <6> to <14>.
<16> The content of the surfactant in the fiber aggregate is 0% by mass or more and 50% by mass or less, preferably 0% by mass or more and 25% by mass or less with respect to the component (b) <6. The kit according to any one of> to <15>.
<17> The total content of alcohol and ketone having 2 or less carbon atoms in the aqueous medium is 0% by mass or more and 40% by mass or less, preferably 0% by mass or more and 30% by mass or less, based on the aqueous medium. The kit according to any one of <6> to <16>, which is more preferably 0% by mass or more and 20% by mass or less.
<18> The content of the surfactant in the aqueous medium is 0% by mass or more and 5% by mass or less, preferably 0% by mass or more and 3% by mass or less, more preferably 0 with respect to the aqueous medium. The kit according to any one of <6> to <17>, which is 1% by mass or more and 1% by mass or less.

<19> A fiber aggregate containing a component (a) a polymer soluble in water and an alcohol or a ketone, and a component (b) a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
A fiber aggregate containing the component (b) in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
A method for applying the liquid composition to the skin, which comprises a step of dissolving the liquid composition in an aqueous medium to obtain a liquid composition.
<20> Application of the liquid composition according to <19> to the skin, wherein the aqueous medium is applied to the surface of the skin and the fiber aggregate is applied on the surface of the skin to dissolve the fiber aggregate in the aqueous medium. Method.
<21> The method for applying the liquid composition to the skin according to <19>, wherein the fiber aggregate is added to the aqueous medium to obtain a liquid composition, and the liquid composition is applied to the skin.
<22> 0 minutes or more and 180 minutes or less, preferably 0 minutes or more and 30 minutes or less, more preferably 0 minutes or more and 10 minutes or less, still more preferably 0 minutes or more and 5 minutes or less after the fiber aggregate is added to the aqueous medium. The method for applying the liquid composition to the skin according to <21>, wherein the liquid composition is applied to the skin within.

<23> A fiber aggregate containing a component (a) a polymer soluble in water and an alcohol or a ketone, and a component (b) a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
Of a fiber aggregate containing the component (b) in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
Use for the production of liquid skin external compositions.

<24> A fiber aggregate containing a component (a) a polymer soluble in water and an alcohol or a ketone, and a component (b) a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
A fiber aggregate containing the component (b) in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
A method for producing a liquid skin external composition, which comprises a step of dissolving in an aqueous medium to obtain a liquid composition.

<25> A liquid skin external composition containing a fiber aggregate formed of a polymer (A) soluble in water and an alcohol or a ketone, a component (B) a poorly water-soluble component, and a component (C) an aqueous medium. And,
The component (C) contains 60% by mass or more of water and contains 60% by mass or more.
A liquid-liquid dispersion liquid skin external composition in which droplets containing the component (B) are dispersed in a liquid containing the component (C) as a main component.
<26> The liquid-liquid dispersion liquid skin external composition according to <25>, wherein the water content is 6% by mass or more and 99.9% by mass or less with respect to the entire composition.
<27> The liquid-liquid dispersion liquid skin external composition according to <25>, wherein the water content is 8% by mass or more and 99% by mass or less, preferably 10% by mass or more and 98% by mass or less with respect to the entire composition. ..
<28> The component (A) is one or more polymers selected from purulan, partially saponified polyvinyl alcohol, low sausible polyvinyl alcohol, polyvinylpyrrolidone, and a methacrylic acid copolymer, preferably polyvinylpyrrolidone and methacryl. The liquid-liquid dispersion liquid skin external composition according to any one of <25> to <27>, which is one or more macromolecules selected from acid copolymers.
<29> The liquid-liquid dispersion liquid according to any one of <25> to <28>, wherein the component (B) contained in the liquid-liquid dispersion liquid skin external composition is contained in an amorphous state. External composition for skin.
<30> The average particle size of the droplet containing the component (B) is 0.001 μm or more and 100 μm or less, preferably 0.001 μm or more and 80 μm or less, and more preferably 0.001 μm or more and 50 μm or less <25>. The liquid-liquid dispersion liquid skin external composition according to any one of <29>.
<31> The liquid-liquid dispersion liquid skin external composition according to any one of <25> to <30>, wherein the component (B) has a melting point of 20 ° C. or higher, preferably 40 ° C. or higher.
<32> The component (B) is one or more selected from polyphenol compounds, ceramides, fat-soluble vitamins, phytosterols, glycyrrhetinic acid or derivatives thereof, steroids or derivatives thereof, and monoterpenes or derivatives thereof. The liquid-liquid dispersion liquid skin external composition according to any one of <25> to <31>.
<33> The total content of alcohol and ketone having 2 or less carbon atoms in the component (C) is 0% by mass or more and 40% by mass or less, preferably 0% by mass or more and 30% by mass or less, more preferably. The liquid-liquid dispersion liquid skin external composition according to any one of <25> to <32>, wherein is 0% by mass or more and 20% by mass or less.
<34> The content of the surfactant in the component (C) is 0% by mass or more and 5% by mass or less, preferably 0% by mass or more and 3% by mass or less, and more preferably 0% by mass or more and 1 The liquid-liquid dispersion liquid skin external composition according to any one of <25> to <33> having a mass% or less.
<35> The content of the surfactant in the composition is 0% by mass or more and 3% by mass or less, preferably 0% by mass or more and 1% by mass or less, more preferably 0 with respect to the entire composition. The liquid-liquid dispersion liquid skin external composition according to any one of <25> to <34>, which is by mass or more and 0.5% by mass or less.

Hereinafter, the present invention will be described in more detail by way of examples. However, the scope of the invention is not limited to such examples. Unless otherwise specified, "%" means "mass%".

[Examples 1 to 4]
(Manufacturing of nanofiber deposits or crushed products thereof)
The components (a) and (b) in the amounts shown in Table 1 were dissolved in ethanol to obtain a solution having a mass% shown in Table 1. No surfactant was used in either case. Using this solution, nanofiber deposits were formed on the surface of the substrate by the electrospinning apparatus described in FIG. 2 of Patent Document 1. The conditions for producing nanofiber deposits were as follows.
In addition, in order to instantly dry and immobilize the homogeneous solution by electrospinning, the solid content ratio (mass%) of the components (a) and the components (b) of the liquid composition shown in Table 1 is the obtained fiber aggregate. It can be equated with the content (mass%) of each component of.
-Applied voltage: 32 kV
・ Distance between capillary and collector: 160 mm
・ Aqueous solution discharge rate: 1 mL / h
・ Environment: 25 ℃, 30% RH
As the non-woven fabric used as the base material, "Benlyse (registered trademark) SE103", which is a non-woven fabric manufactured by Asahi Kasei Corporation, was used.
As the crushed product, the nanofiber deposit was crushed for 5 minutes using a commercially available cutter mill to obtain a crushed product.

(X-ray diffraction evaluation of fiber aggregate)
Table 1 shows the results of X-ray diffraction evaluation. This evaluation was measured under the following conditions using a powder X-ray diffractometer (MiniFlex 600, manufactured by Rigaku Co., Ltd.).
Preparation of measurement sample: A crushed nanofiber deposit was filled in a measurement cell and pressure was applied to prepare a smooth pellet having an area of 320 mm2 and a thickness of 1 mm.
X-ray diffraction analysis conditions: Step angle 0.01 °, scan speed 10 ° / min, measurement range: diffraction angle 2θ = 5-40 ° X-ray source: Cu / Kα-radiation, tube voltage: 15 kv, tube current: 30 mA
The above evaluation was also carried out on the poorly water-soluble component contained in the nanofiber, and the diffraction angle at which the crystal peak derived from the crystal of the poorly water-soluble component appears was grasped.
Then, in the evaluation of the nanofiber deposit, when the measurement peak derived from the crystal of the poorly water-soluble component contained did not appear, it was determined that the poorly water-soluble component was contained in an amorphous state.

(Solid-state NMR evaluation of fiber aggregates)
The solid-state NMR evaluation described above was performed on the nanofiber deposits of Example 2.
Here, the diffusion coefficient D of the spin diffusion of the organic solid was set to 10 ^ (-12) cm ² / s.
As a result, the relaxation times T1ρ obtained from the polymer forming the fiber and the poorly water-soluble functional component were calculated to be 9.3 ms and 10.1 ms, respectively, and the particle size of the poorly water-soluble functional component was 3 nm. It was estimated as follows.

[Test Examples 1 to 13]
The nanofiber deposits of Examples 1 to 4 were placed on the slide glass, the cover glass was placed on the slide glass, and the aqueous medium of Table 2 (c) was applied through the gap between the slide glass and the cover glass. Within 30 seconds after application of the aqueous medium, an image is taken with an optical microscope, and if there are droplets, they are magnified 50 to 1000 times depending on the size of the droplets and observed, and an image is taken to take an average particle. The diameter was calculated.
Further, (b) the poorly water-soluble component and (c) the Hansen solubility of the aqueous medium were estimated using the commercially available Hansen solubility parameter estimation software HSPiP.
The fiber thickness of the nanofibers in the nanofiber deposits was determined by scanning electron microscope (SEM) observation.

(Microscopic observation)
FIGS. 1 and 2 show the optical microscopes of Test Examples 3 and 5, and FIGS. 3 and 4 show the optical microscopes of Test Examples 1 and 2. 1 and 2 show that the droplet containing the component (B) is a liquid-liquid dispersed liquid skin external composition dispersed in a liquid containing the component (C) as a main component. 3 and 4 show that the component (B) is completely dissolved in the liquid containing the component (C) as the main component, and there are no droplets containing the component (B). No droplets or precipitates were observed even after 30 seconds had passed.

(Observation with a polarizing microscope)
The nanofiber deposit was placed on the slide glass, the cover glass was placed on the slide glass, and the component (C) in Table 2 was applied from the gap between the slide glass and the cover glass. Within 30 seconds after application of the aqueous medium, observe with a polarizing microscope, evaluate the polarization characteristics and birefringence characteristics if there are droplets, and if there is no color change or light and shade, the droplets are amorphous. It was judged to be in a state.

(Observation of changes in droplet state over time)
The nanofiber deposit of Example 2 was placed on the slide glass, the cover glass was placed on the slide glass, and the component (C) in Table 2 was applied from the gap between the slide glass and the cover glass. Then, the droplet was magnified 50 to 1000 times according to the size of the droplet and observed with a polarizing microscope, and the change from the amorphous state to the crystalline state of the droplet with time was observed.
The results are shown in Table 3.

In Test Example 13, the value indicated by the mass (mg) of the fiber aggregate / the mass (mg) of the aqueous medium was small, that is, the content ratio of the poorly water-soluble component was small, so that the droplet could not be formed. Conceivable.

From the above results, the fiber aggregate obtained in the examples was obtained by immobilizing a poorly water-soluble component in a fine particle size and an amorphous state. Further, the liquid skin external composition obtained by using these is excellent in applicability to the skin because the poorly water-soluble component is dissolved in the aqueous component at a high concentration (supersaturation).

Claims (13)

It is a fiber aggregate
Containing component (a) polyvinylpyrrolidone and component (b) sparingly water-soluble component,
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
The component (b) is contained in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
A fiber in which the particle size of the component (b) contained in the fiber is 0.1 nm or more and 10 nm or less, and the component (b) is contained in the fiber in an amorphous form. Aggregation. The fiber aggregate according to claim 1, which is used for producing a composition for external use on liquid skin. A liquid skin external composition manufacturing kit comprising the fiber aggregate according to claim 1 or 2 and an aqueous medium. The kit according to claim 3 , wherein the average fiber diameter of the fibers in the fiber aggregate is 20 nm or more and 5000 nm or less. Claims 3 to 4 in which the ratio of the fiber aggregate to the aqueous medium (mass of the fiber aggregate (mg) / mass of the aqueous medium (mg)) is 0.0001 mg / mg or more and 10 mg / mg or less. The kit according to any one of the above. Claims 3 to 5 in which the mass ratio of the component (a) to the component (b) in the aggregate (mass of the component (a) / mass of the component (b)) is 2 or more and 49 or less. The kit described in any one of the items. The kit according to any one of claims 3 to 6 , wherein the content of the surfactant in the fiber aggregate is 0% by mass or more and 50% by mass or less with respect to the component (b). It is a fiber aggregate and contains a component (a) a polymer soluble in polyvinylpyrrolidone and a component (b) a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
The component (b) is contained in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
A fiber assembly in which the particle size of the component (b) contained in the fiber is 0.1 nm or more and 10 nm or less, and the component (b) is contained in the fiber in an amorphous form. Body,
A method for applying the liquid composition to the skin, which comprises a step of dissolving the liquid composition in an aqueous medium to obtain a liquid composition. The method for applying the liquid composition to the skin according to claim 8 , wherein the aqueous medium is applied to the surface of the skin, and the fiber aggregate is applied on the surface of the skin to dissolve the fiber aggregate in the aqueous medium. The method for applying the liquid composition to the skin according to claim 9 , wherein the fiber aggregate is added to the aqueous medium to obtain a liquid composition, and the liquid composition is applied to the skin. It is a fiber aggregate and contains a component (a) polyvinylpyrrolidone and a component (b) a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
The component (b) is contained in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
A fiber assembly in which the particle size of the component (b) contained in the fiber is 0.1 nm or more and 10 nm or less, and the component (b) is contained in the fiber in an amorphous form. of a body,
Use for the production of liquid skin external compositions. It is a fiber aggregate and contains a component (a) polyvinylpyrrolidone and a component (b) a poorly water-soluble component.
50% by mass or more and 98% by mass or less of the component (a) with respect to the entire fiber aggregate,
The component (b) is contained in an amount of 2% by mass or more and 40% by mass or less with respect to the entire fiber aggregate.
A fiber assembly in which the particle size of the component (b) contained in the fiber is 0.1 nm or more and 10 nm or less, and the component (b) is contained in the fiber in an amorphous form. Body,
A method for producing a liquid skin external composition, which comprises a step of dissolving in an aqueous medium to obtain a liquid composition. A liquid skin external composition containing a fiber aggregate formed of the component (A) polyvinylpyrrolidone , the component (B) a poorly water-soluble component, and the component (C) an aqueous medium.
The component (C) contains 60% by mass or more of water and contains 60% by mass or more.
Liquid-liquid dispersion liquid in which the droplets containing the component (B) are amorphous and dispersed in a liquid containing the component (C) as a main component in a state where the average particle size is 0.001 μm or more and 100 μm or less. External composition for skin.

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