WO2025047639A1 - Composition - Google Patents

Abstract

Provided is a composition or the like in which the dispersibility of bakuchiol in a water-soluble solvent is improved.　A composition according to the present disclosure contains: bakuchiol; a dissolving agent; and a nonionic surfactant and/or an anionic surfactant.

Description

Composition

This disclosure relates to a composition.

Bakuchiol is a natural ingredient contained in Psoralea corylifolia , and it has been reported that the bakuchiol has a retinol-like effect. For this reason, various studies have been conducted on the addition of the bakuchiol to cosmetics and the like.

The first object of the present disclosure is, for example, to provide a composition in which the dispersibility of bactiol in a water-soluble solvent is improved.

A second object of the present disclosure is to provide a composition in which the thermal stability of carotenoids, particularly retinoids, is improved.

The third object of the present disclosure is, for example, to provide a composition that improves the permeability of bactiol through the stratum corneum.

The fourth object of the present disclosure is, for example, to provide a composition containing bactiol that is easy to handle.

In order to achieve the first objective, the composition of the present disclosure (hereinafter also referred to as the "first composition") contains bactiol, a solvent, and a nonionic surfactant and/or anionic surfactant.

In order to achieve the second object, the composition of the present disclosure (hereinafter also referred to as the "second composition") contains bactiol and a carotenoid,
The mass ratio (B:C) of the bactiol (B) to the carotenoid (C) is 1:10 to 2:1.

In order to achieve the third object, the composition of the present disclosure (hereinafter also referred to as the "third composition") contains liposomes,
The liposomes contain bactiol, complex lipids, and sterols.

In order to achieve the fourth object, the composition of the present disclosure (hereinafter also referred to as the "fourth composition") comprises bactiol and silica,
The bactiol is supported on the silica.

The first composition of the present disclosure can provide, for example, a composition in which the dispersibility of bactiol in a water-soluble solvent is improved.

The second composition of the present disclosure can provide, for example, a composition in which the thermal stability of carotenoids, particularly retinoids, is improved.

The third composition of the present disclosure can provide, for example, a composition that improves the permeability of bactiol through the stratum corneum.

The fourth composition of the present disclosure can provide, for example, a composition containing bactiol that is easy to handle.

FIG. 1 is a photograph showing the dispersibility in a solvent of the first composition of the present disclosure in Example 1. FIG. 2 is a graph showing the distribution of average particle sizes of oil droplets contained in the first composition of the present disclosure in Example 1. FIG. 3 is a photograph showing the stratum corneum permeability of the third composition of the present disclosure in Example 3.

The present disclosure will be explained in detail below with examples. Unless otherwise specified, each disclosure may refer to the explanations of other disclosures.

<Definition>
In this specification, "bakuchiol" means a compound represented by 4-[(1E,3S)-3-ethenyl-3,7-dimethylocta-1,6-dienyl]phenol. It is known that the bakuchiol is extracted from the seeds of Psoralea corylifolia , an annual plant of the legume family. The bakuchiol can be a compound represented by the following chemical formula (1). The bakuchiol may be, for example, a phenoxide ion. The bakuchiol may be, for example, esterified.

In this specification, "surfactant" refers to a compound having a hydrophilic group and a hydrophobic group (lipophilic group). Examples of the surfactant include anionic (negative ionic) surfactants, cationic (positive ionic) surfactants, zwitterionic surfactants, and nonionic (nonionic) surfactants. The anionic surfactant refers to a surfactant that dissociates into anions in an aqueous solution. The cationic surfactant refers to a surfactant that dissociates into cations in an aqueous solution. The zwitterionic surfactant refers to a surfactant that dissociates into cations or anions in an aqueous solution depending on the pH of the aqueous solution. The nonionic surfactant refers to a surfactant that does not dissociate into ions in an aqueous solution.

In this specification, "carotenoid" refers to a naturally occurring pigment component and a compound that has antioxidant properties.

In this specification, "sterols" refers to compounds that contain a cyclopentanophenanthrene carbon skeleton.

In this specification, "oil gel" refers to a gel-like oil agent (oily component) thickened with a lipophilic gelling agent. The oil gel can be prepared, for example, by adding an oily gelling agent to an oil agent.

In this specification, "oil gel particle" refers to one or more particles that are composed of oil gel and have a desired component dissolved or dispersed in the oil of the oil gel.

As used herein, "liposome" refers to a vesicle having a lipid bilayer membrane dispersed in an aqueous solvent.

<First composition>
In one aspect, the present disclosure provides a composition (hereinafter also referred to as "first composition") in which the dispersibility of bactiol in a water-soluble solvent is improved. As described above, the first composition of the present disclosure is characterized by including bactiol, a solvent, and a nonionic surfactant and/or anionic surfactant, and other configurations and conditions are not particularly limited.

It is known that bactiol is lipophilic (hydrophobic) and therefore difficult to disperse in an aqueous solvent. As a result of intensive research, the present inventors have discovered that bactiol can be dispersed in an aqueous solvent by combining bactiol with a solvent and a nonionic surfactant and/or anionic surfactant, and more specifically, that bactiol can be dispersed by forming a complex such as a micelle with a nonionic surfactant and/or anionic surfactant, and have established the present disclosure. Therefore, according to the present disclosure, a composition can be provided in which the dispersibility of bactiol in an aqueous solvent is improved.

The bactiol may be an isolated or purified compound, or a composition containing bactiol. Examples of the composition containing bactiol include an extract containing bactiol; a crude product of the extract, a dried product of the extract, a freeze-dried product of the extract, a spray-dried product, or other processed product of the extract. The bactiol may be prepared in-house, or may be a commercially available product. When a commercially available product is used, an example is bactiol manufactured by BIB Corporation.

The extract containing bactiol can be produced, for example, by carrying out a solvent extraction on a plant containing bactiol. Examples of the plant containing bactiol include Psoralea corylifolia and Otholobium pubescens . One or more types of the plant may be used. The plant material to be subjected to the extraction may be an individual plant or a part of the plant. Examples of the part of the plant include roots, rhizomes, leaves, stems, whole flowers, or a mixture thereof. The material may be the plant itself as it is collected, or may be a processed product obtained by drying and/or crushing.

The solvent used for extracting bactiol may be, for example, an aqueous solvent such as water or a buffer solution; a lower alcohol or a water-containing lower alcohol such as methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, or isobutanol; propylene glycol, butylene glycol (e.g., 1,3-butylene glycol, 1,2-butylene glycol, 1,4-butylene glycol, etc., hereinafter the same), 1,5-pentanediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,3,5-pentanetriol, Examples of the solvent include polyhydric alcohols or hydrous polyhydric alcohols such as glycerin (e.g., concentrated glycerin) and polyethylene glycol (e.g., molecular weight 100 to 100,000); organic solvents such as acetone, ethyl acetate, diethyl ether, dimethyl ether, ethyl methyl ether, dioxane, hexane, acetonitrile, xylene, benzene, chloroform, carbon tetrachloride, phenol, and toluene; acids (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, etc.) or alkalis (sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia, etc.) whose normality has been appropriately adjusted; and the like. The solvents may be used alone or in combination.

The treatment of the treated material may be, for example, decomposition by adding acid (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, organic acid, etc.) or alkali (sodium hydroxide, calcium hydroxide, ammonia, etc.); fermentation or metabolic conversion by microorganisms; component adsorption by ion exchange resins, activated carbon, diatomaceous earth, etc.; fractionation using chromatography with various separation modes (ion exchange, hydrophilic adsorption, hydrophobic adsorption, size exclusion, ligand exchange, affinity, etc.); filtration using filter paper, membrane filters, ultrafiltration membranes, etc.; pressurization or decompression; heating or cooling; drying or freeze-drying; pH adjustment; deodorization; decolorization; long-term static storage; etc. One type of the treatment may be performed alone, or multiple types may be performed.

The content of the bactiol is, for example, preferably 0.001 to 5% by mass, more preferably 0.01 to 3% by mass, and even more preferably 0.1 to 2% by mass (e.g., 0.2% by mass, 1% by mass) based on the total mass of the first composition of the present disclosure.

The solvent (solubilizer) may be, for example, a liquid oil, polyhydric alcohol, etc. The oil may be, for example, an ester oil, a hydrocarbon oil, an ether oil, etc.

The ester oil may be, for example, glycerin fatty acid ester. Examples of the glycerin fatty acid ester include triester oils such as triethylhexanoin, glyceryl tri-2-ethylhexanoate, glyceryl tri(caprylic acid/capric acid), olive oil, jojoba oil, macadamia nut oil, medfoam oil, castor oil, safflower oil, sunflower oil, avocado oil, canola oil, apricot kernel oil, rice germ oil, and rice bran oil; and glycerin fatty acid triesters such as dipentaerythrityl tetraisostearate. The ester oil is preferably glyceryl tri(caprylic acid/capric acid), because it is highly safe for use in human cosmetics and topical agents, has excellent versatility in formulation design, and is highly available worldwide.

The polyhydric alcohol may be, for example, a monohydric alcohol such as ethyl alcohol (ethanol), normal propyl alcohol, or isopropyl alcohol; or a dihydric alcohol such as butylene glycol (for example, 1,3-butylene glycol), dipropylene glycol, or propylene glycol. The polyhydric alcohol is preferably butylene glycol, since it can improve the dispersibility of the oil droplets described below.

The content of the solvent is, for example, from more than 0% by mass to 90% by mass based on the total mass of the first composition of the present disclosure, and is preferably from more than 0% by mass to 5% by mass, 10 to 75% by mass, or 25 to 50% by mass, since this can improve the dispersibility of the bactiol. The solvent is of one or more types. In the latter case, the content of the solvent may be the content of one type of solvent or the total content of multiple types of solvents, but is preferably the total content of multiple types of solvents.

When there are multiple types of solvents, the combination of the solvents is preferably, for example, a combination of ester oil and polyhydric alcohol, since this can improve the dispersibility of the bactiol, and more preferably a combination of caprylic/capric triglyceride and butylene glycol.

Examples of the nonionic surfactant include ethylene oxide condensation type nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene steryl ethers, polyoxyethylene polyoxypropylene alkyl ethers, polyoxyethylene fatty acid esters, polyoxyethylene polyhydric alcohol fatty acid esters, polyoxyethylene hydrogenated castor oils, and polyoxyethylene sorbitan fatty acid esters; polyhydric alcohol ester type nonionic surfactants such as glycol fatty acid esters, glycerin fatty acid esters, sorbitan fatty acid esters, sucrose fatty acid esters, and polyglycerin fatty acid esters; polyhydric alcohol condensation type nonionic surfactants such as fatty acid alkanolamides and alkyl glycosides; and the like. Ethylene oxide condensation type nonionic surfactants are preferred, and polyoxyethylene polyoxypropylene alkyl ethers are even more preferred due to their excellent dispersibility. Examples of the polyoxyethylene polyoxypropylene alkyl ethers include polyoxyethylene polyoxypropylene decyl tetradecyl ether (e.g., PPG-6 decyl tetradeceth-20, PPG-6 decyl tetradeceth-30), polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene monobutyl ether, polyoxyethylene polyoxypropylene, hydrogenated lanolin, polyoxyethylene polyoxypropylene glycerin ether, and the like.

The anionic surfactant may be, for example, a carboxylate-based anionic surfactant such as a carboxylate or an alkyl ether carboxylate; a higher alcohol-based anionic surfactant such as an alkyl sulfate or an alkyl ether sulfate; a sulfonic acid-based anionic surfactant such as an acyl isethionate or an alkyl sulfonate; a peptide-based anionic surfactant such as an acyl peptide salt; an olefin-based anionic surfactant such as an α-olefin sulfonate; an amino acid-based anionic surfactant such as an acyl sarcosine salt, an acyl methyl alanine salt, an acyl glutamate salt, an acyl aspartate salt, or an acyl glycine salt; a taurine-based anionic surfactant such as an acyl methyl taurine salt; a lactic acid-based anionic surfactant such as an acyl lactate; and the like.

The content of the nonionic surfactant and/or anionic surfactant is preferably, for example, 2 to 20 mass % based on the total mass of the first composition. The surfactant may be one type or multiple types. In the latter case, the content of the surfactant may be the content of one type of surfactant or the total content of multiple types of surfactants, but is preferably the total content of multiple types of surfactants.

The first composition of the present disclosure may further include a block copolymer. The first composition of the present disclosure can promote emulsification (emulsion formation) of bactiol by including the block copolymer, and therefore the dispersibility of the first composition of the present disclosure can be improved. The block copolymer is preferably a self-organizing block copolymer (self-organizing block copolymer) since it can further promote emulsification of bactiol. Examples of the block copolymer include polyamino acid-polyethylene glycol copolymers such as oligopeptide-56 amide PEG-75 methyl ether; polylactic acid-polyethylene glycol block copolymers; polylactic acid-polyglycolic acid block copolymers; polysarcosine-polyethylene glycol block copolymers; polyoxazoline-polysiloxane block copolymers; and the like. The block copolymer is preferably a polyamino acid-polyethylene glycol copolymer, and more preferably oligopeptide-56 amide PEG-75 methyl ether, since it can impart emulsion stability.

When the first composition of the present disclosure contains the block copolymer, the content of the block copolymer is, for example, 0.02 to 2 mass% based on the total mass of the first composition, and more preferably 0.05 to 1.5 mass%, or 0.1 to 1 mass%, since this can improve the dispersibility of the bactiol. The block copolymer is of one type or multiple types. In the latter case, the content of the block copolymer may be the content of one type of block copolymer or the total content of multiple types of block copolymers, but is preferably the total content of multiple types of block copolymers.

The first composition of the present disclosure may further include a dispersion medium. For example, when the dispersoid is dissolved in the dispersion medium, the dispersion medium may also be called a solvent or a solvent (hereinafter the same). For example, the dispersion medium may be an aqueous solvent. For example, the aqueous solvent may be purified water, distilled water, ion-exchanged water, pure water, ultrapure water, etc.

When the first composition of the present disclosure contains the dispersion medium, the amount of the dispersion medium is not particularly limited and can be the remainder of the other components of the first composition. The amount of the dispersion medium is, for example, preferably from more than 0% to 90% by mass, more preferably from more than 0% to 10% by mass, and even more preferably from more than 0% to 5% by mass, based on the total mass of the first composition of the present disclosure.

The first composition of the present disclosure is preferably an oil-in-water (o/w) emulsion. The oil-in-water emulsion is composed of an aqueous dispersible continuous phase and an oily dispersed discontinuous phase, and refers to a state in which oil droplets are dispersed in the aqueous phase. The oil-in-water emulsion contains an aqueous phase as an outer phase, and when applied to the skin, it gives a lighter feeling of compatibility with the skin than a water-in-oil emulsion, and is therefore suitable for lotions and the like. The emulsion is preferably a nanoemulsion and/or a microemulsion. This allows the first composition of the present disclosure to maintain a transparent or translucent appearance. In the present disclosure, the "nanoemulsion" refers to, for example, an emulsion characterized by a dispersion system of micro-sized micelles. In the present disclosure, the "microemulsion" refers to, for example, an emulsion having a fine particle size (for example, several to 100 nm).

The oil droplets may contain bactiol, a solvent, a nonionic surfactant, and/or an anionic surfactant. The average particle size of the oil droplets is, for example, 100 nm or less, and is preferably 10 to 75 nm, and more preferably 20 to 60 nm, since this can improve dispersibility and stability over time. The average particle size of the oil droplets can be measured by dynamic light scattering. Specifically, the average particle size can be determined, for example, by using a Zetasizer Nano from Malvern Panalytical Co., Ltd., by placing a 100-fold diluted target composition in a sample cell in the device and measuring the average particle size distribution of the oil droplets. Note that the measurement is calibrated using standard particles.

The transmittance (the ratio of the intensity of outgoing light to the intensity of incoming light) of the first composition of the present disclosure is not particularly limited, but is preferably 50% or more, more preferably 60% or more, and even more preferably 70% or more, because this improves stability over time and aesthetics. The transmittance is measured with a spectrophotometer (cell optical path length: 10 mm, light wavelength: 600 nm). The spectrophotometer may be, for example, an ultraviolet-visible-near infrared spectrophotometer V-770 (JASCO Corporation).

The transparency of the first composition of the present disclosure can be evaluated, for example, by its transparency. The transparency can be measured, for example, using a turbidity meter. The lower limit of the turbidity is 0 NTU, more than 0 NTU, and preferably 10 NTU or more. The upper limit of the turbidity is, for example, less than 200 NTU, and is preferably less than 150 NTU, since this improves stability over time and aesthetics.

The first composition of the present disclosure may contain any other ingredient typically used in cosmetics, such as a moisturizer, a sequestering agent, a neutralizing agent, a pH adjuster, an antioxidant, a preservative, etc.

The first composition of the present disclosure has improved dispersibility in the solvent. The dispersibility can be evaluated, for example, using the degree of precipitation (solubility) of the target composition as an evaluation. Specifically, when the degree of precipitation is used as an evaluation, the target composition can be stored for one month and then visually evaluated after storage. In the evaluation, if no precipitation is confirmed in the target composition, the target composition can be evaluated as having excellent dispersibility in the solvent, i.e., having improved dispersibility.

The method for producing the first composition of the present disclosure can be, for example, by mixing bactiol, the solvent, and the nonionic surfactant and/or the anionic surfactant. The mixing is preferably carried out in the presence of the aqueous solvent. When carried out in the presence of the aqueous solvent, the method for producing the first composition can be, for example, by adding the bactiol, the solvent, the nonionic surfactant, and/or the anionic surfactant to the aqueous solvent, and then mixing to the extent that the bactiol is dispersed in the resulting liquid.

The first composition may be prepared so that the bactiol forms micelles. In this case, the method for preparing the first composition may refer to, for example, the method described in Example 1. As an example, the method for preparing the first composition includes preparing an oil-in-water emulsion containing bactiol, a solvent, and the nonionic surfactant and/or the anionic surfactant in the presence of a dispersion medium such as the aqueous solvent.

The oil-in-water emulsion can be produced by a known method for dispersing oil in the aqueous solvent. The oil-in-water emulsion can be prepared, for example, by mixing bactiol, a solvent, and the nonionic surfactant and/or the anionic surfactant, and homogenizing or dispersing in the dispersion medium. The mixing can be performed, for example, by manual shaking, stirring with a stirrer or a stirring blade, or using an ultrasonic vibrator. The mixing temperature is not particularly limited, for example, as long as the mixture can be dispersed at the temperature, and is preferably 55 to 80°C, and more preferably 70 to 80°C. The mixing time is not particularly limited, for example, as long as the bactiol or the like can be dispersed, and is preferably 0.25 to 2 hours, and more preferably 0.5 to 1 hour.

In the mixing, the optional other components may be added. When the optional other component is a preservative, the preservative may be, for example, phenoxyethanol.

The dispersion medium preferably contains, for example, a block copolymer. When the dispersion medium contains the block copolymer, the method for producing the first composition preferably includes, for example, mixing the dispersion medium and the block copolymer before, during, or after the formation of the oil-in-water emulsion, and homogenizing or dispersing the block copolymer in the dispersion medium. The mixing temperature is not particularly limited, for example, as long as it is a temperature at which the block copolymer can be dispersed in the dispersion medium, and is preferably, for example, 60 to 85°C. The mixing time is not particularly limited, for example, as long as it is a time at which the block copolymer can be dispersed in the dispersion medium, and is preferably, for example, 0.5 to 3 hours.

After the oil-in-water emulsion is formed, the method for producing the first composition preferably includes, for example, a micronization treatment of the oil droplets of the oil-in-water emulsion. By including the micronization treatment in the method for producing the first composition, for example, the dispersibility and temporal stability of bactiol in the obtained composition can be further improved. The micronization treatment can be, for example, a nanoparticle treatment for micronizing the oil droplets to nano size. The micronization treatment can be performed, for example, using a known method. The micronization treatment can be performed, for example, by ultrasonic emulsification using an ultrasonic processing device, a high-pressure emulsifier, or the like. When the micronization treatment is performed using a high-pressure emulsifier, the pressure of the micronization treatment is, for example, 20 to 200 MPa, preferably 50 MPa. The number of pressure passes of the nanoparticle treatment is, for example, 1 to 10 passes, preferably 1 to 3 passes. By increasing the pressure and number of passes in the micronization treatment, the average particle size of the oil droplets in the oil-in-water emulsion can be relatively small after the micronization treatment. As a result, the method for producing the first composition can further improve, for example, dispersibility, stability over time, transparency (transmittance), etc., and can further suppress turbidity.

The average particle size of the oil droplets can be adjusted, for example, by adjusting the content of bactiol, solvent, nonionic surfactant, and/or anionic surfactant, etc. relative to the total amount of the first composition of the present disclosure.

<Second Composition>
In another aspect, the present disclosure provides a composition (hereinafter also referred to as "second composition") in which the thermal stability of carotenoid is improved. As described above, the second composition of the present disclosure contains bactiol and a carotenoid, and the mass ratio (B:C) of the bactiol (B) to the carotenoid (C) is 1:10 to 2:1. The second composition of the present disclosure contains bactiol and a carotenoid, and the mass ratio (B:C) of the bactiol (B) to the carotenoid (C) is 1:10 to 2:1, and other configurations and conditions are not particularly limited. According to the second composition of the present disclosure, for example, the thermal stability of carotenoid can be improved. The description of the first composition of the present disclosure can be applied to the second composition of the present disclosure.

Retinol is known to be unstable and easily decomposed when exposed to heat, etc. As a result of intensive research, the inventors have constructed a composition combining bactiol and carotenoid in a specified ratio, and have found that the carotenoid, particularly the retinoid, contained in said composition has higher thermal stability than retinoid alone, leading to the establishment of the present disclosure. Therefore, according to the present disclosure, it is possible to provide a composition in which the thermal stability of carotenoid, particularly the retinoid, is improved.

The carotenoids include carotenes such as β-carotene, α-carotene, and lycopene; xanthophylls such as lutein, canthaxanthin, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, violaxanthin, lycopene, crocin, and capsanthin; and apocarotenoids such as retinol, bixin, norbixin, and crocetin. The α-carotene, β-carotene, and β-cryptoxanthin are vitamin A precursor (provitamin A) carotenoids, and can be converted to retinol (vitamin A) in the body. The vitamin A precursor carotenoid and the retinol can also be called retinoids. The carotenoids include carotenoid decomposition products. The retinoids can also be called carotenoid decomposition products, for example, since they are generated by the decomposition of the carotenoids in the body.

Examples of the retinoid include retinol (vitamin A), retinal (vitamin A aldehyde), retinoic acid (vitamin A acid), retinol propionate, retinol acetate, retinol linoleate, and retinol palmitate.

The second composition of the present disclosure preferably contains the bactiol (B) and the carotenoid (C) in a mass ratio (B:C) of 1:10 to 2:1. It is even more preferable that the mass ratio (B:C) is 1:4 to 1:2, or 1:2 to 2:1, since this further improves thermal stability.

The content of the bactiol is, for example, preferably 0.001 to 5 mass%, 0.01 to 2.5 mass%, or 0.1 to 1 mass% based on the total mass of the second composition.

The content of the carotenoid is preferably, for example, 0.001 to 5 mass%, 0.01 to 2.5 mass%, or 0.1 to 1 mass% based on the total mass of the second composition.

The second composition of the present disclosure may further contain an oil. Examples of the oil include liquid oils and fats, ester oils, silicone oils, hydrocarbon oils, higher alcohols, fatty acids, etc., used in external compositions such as cosmetics. The oil is preferably silicone oil, since it can impart a moist and smooth feel as well as good skin compatibility when made into an oil gel composition as described below. The oil is preferably hydrocarbon oil, since it can impart a moist feel as well as good skin compatibility when made into an oil gel composition as described below.

Examples of the liquid oils and fats include liquid oils and fats derived from animals and plants, such as linseed oil, camellia oil, macadamia nut oil, corn oil, olive oil, avocado oil, camellia oil, castor oil, safflower oil, apricot kernel oil, cinnamon oil, jojoba oil, grape oil, sunflower oil, almond oil, rapeseed oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, cottonseed oil, soybean oil, peanut oil, tea seed oil, evening primrose oil, egg yolk oil, and liver oil. The liquid oils and fats to be used may be synthetic products or commercially available products. When using commercially available products, examples include DHA-55 (manufactured by Maruha Nichiro Co., Ltd.), safflower oil (manufactured by Nisshin Oillio Co., Ltd.), Oryza salad oil (manufactured by Oryza Oil Chemical Co., Ltd.), edible olive oil (manufactured by J-Oil Mills Co., Ltd.), linseed oil S (manufactured by Nippon Flour Mills Co., Ltd.), and Coconard ML (manufactured by Kao Corporation).

Examples of the ester oils include isononanoic acid esters such as isononyl isononanoate; octanoic acid esters such as cetyl octanoate; isooctanoic acid esters such as glycerin tri-2-ethylhexanoate and pentaerythritol tetra-2-ethylhexanoate; lauric acid esters such as hexyl laurate; myristate acid esters such as isopropyl myristate and octyldodecyl myristate; palmitic acid esters such as octyl palmitate; stearic acid esters such as isocetyl stearate; isostearic acid esters such as isopropyl isostearate; isopalmitic acid esters such as octyl isopalmitate; oleic acid esters such as isodecyl oleate; adipic acid diesters such as diisopropyl adipate; sebacate diesters such as diethyl sebacate; diisostearyl malate; and the like. The ester oil is preferably isononyl isononanoate, for example, because when made into an oil gel composition as described below, it has softness when crushed on the skin and can impart a transparent appearance and a moist feel to the oil gel composition.

Examples of the silicone oil include linear silicones such as dimethylpolysiloxane, methylphenylpolysiloxane, and methylhydrogenpolysiloxane, cyclic silicones such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexasiloxane, amino-modified silicone oil, polyether-modified silicone oil, carboxy-modified silicone oil, alkyl-modified silicone oil, ammonium salt-modified silicone oil, and fluorine-modified silicone oil.

Examples of the hydrocarbon oil include liquid paraffin, squalane, squalene, pristane, isoparaffin, α-olefin oligomer, and petrolatum.

Examples of the higher alcohol include behenyl alcohol, cetyl alcohol, stearyl alcohol, myristyl alcohol, cetostearyl alcohol, isostearyl alcohol, monostearyl glycerin ether (batyl alcohol), lauryl alcohol, hexadecyl alcohol, octyldodecanol, oleyl alcohol, 2-decyltetradecynol, lanolin alcohol, etc. Octyldodecanol is preferred as the higher alcohol, because when made into an oil gel composition as described below, it has a softness when pressed against the skin and can impart a transparent appearance and a moist feel to the oil gel composition.

Examples of the fatty acids include oleic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, linoleic acid, arachidonic acid, lauric acid, myristic acid, palmitic acid, and stearic acid.

The oil agent may be, for example, a solid or liquid at room temperature. One type of oil agent or a combination of multiple types of oil agents may be used.

When the second composition is an oil gel composition as described below, the oil is preferably a composition containing a high proportion of liquid oil, for example, from the viewpoint of imparting softness to the oil gel, from the viewpoint of external transparency, and from the viewpoint of adjusting the IOB value, and one type or a combination of multiple types can be contained in the oil gel depending on the specific purpose.

When preparing the transparent oil gel composition, it is preferable to use an oil agent that has a refractive index close to the refractive index of water, 1.333, and has a predetermined balance between organicity and inorganicity. In the physicochemical properties of the oil agent, the properties of the oil agent that are mainly due to the van der Waals forces are called "organic". In addition, the properties of the oil agent that are mainly due to the electrical affinity of the oil agent are called "inorganic". Therefore, the properties of the oil agent can be evaluated by evaluating the compound in terms of the combination of "organic" and "inorganic". Specifically, regarding the "organic" and "inorganic" properties of the oil agent, unique characteristic values called organic value (Organic Value = OV) and inorganic value (Inorganic Value = IV) are assigned to each compound of the oil agent, and the organic value and inorganic value of each compound are compared and adjusted to select an oil agent suitable for a transparent oil gel composition.

The upper limit of the IOB value of the oil is preferably 0.85 or less, more preferably 0.84 or less, and even more preferably 0.83. The IOB value represents the ratio of inorganic value and organic value (Inorganic Organic Balance) calculated based on the organic conceptual diagram (Fujita Atsushi, Prediction of Organic Compounds and Organic Conceptual Diagram, Chemistry Area Vol. 11, No. 10 (1957), pages 719-725), and is the value obtained by dividing the inorganic value by the organic value. When multiple types of oils are included, the IOB value of the oil after mixing can be calculated as a weighted average of the IOB values of each oil. If the IOB value of the oil after mixing is 0.85 or less, the second composition can obtain a moist feeling characteristic of an oil gel. The IOB value may be 0, for example, as in squalane, which is a hydrocarbon oil, but is more preferably greater than 0, more preferably 0.01 or more, and even more preferably 0.015 or more.

The oil agent may further contain oil-soluble dyes (Red 225, etc.), organic pigments (Orange No. 204, Red No. 202, etc.), colorants (Orange No. 205, Yellow No. 4, Blue No. 1, etc.) lakes (lakes with zirconium, barium, aluminum, etc.), natural pigments (chlorophyll, β-carotene, etc.), inorganic pigment powders such as yellow iron oxide, red iron oxide, black iron oxide, titanium oxide, zinc oxide, etc. (hydrophobized products are preferred), pearl pigments such as titanium mica, glitter agents made of colored plate-like resins, etc.

When the second composition of the present disclosure contains the oil, the content of the oil is, for example, 50 mass% or more, preferably 55 mass% or more, and more preferably 60 mass% or more, based on the total mass of the second composition. The content of the oil is, for example, 99 mass% or less, preferably 98.5 mass% or less, and more preferably 98.1 mass% or less, based on the total mass of the second composition. When the second composition is an oil gel composition described below, the standard for the content of the oil is the total mass of the oil gel composition.

The second composition of the present disclosure may further contain a gelling agent. The gelling agent is, for example, an ingredient that has the effect of gelling an oil in a transparent to translucent state, imparting viscosity over a wide range, and improving stability over time and the feel when applied to the skin. Examples of the gelling agent include dextrin fatty acid esters, inulin fatty acid esters, and amino acid-based oil gelling agents.

The dextrin fatty acid ester is, for example, an ester of dextrin with a fatty acid or a fatty acid derivative, preferably an ester of a higher fatty acid having 8 to 22 carbon atoms. The average degree of glycopolymerization of the dextrin is preferably 3 to 150, and the degree of fatty acid substitution per glucose unit of the dextrin is preferably 1.5 to 1.7. Examples of the dextrin fatty acid ester include dextrin octanoate, dextrin laurate, dextrin palmitate, dextrin myristate, dextrin stearate, dextrin behenate, coconut oil fatty acid dextrin, and dextrin (palmitate/octanoate). The dextrin fatty acid ester may be a synthetic product or a commercially available product. Commercially available products of the dextrin fatty acid ester include, for example, "Leopearl KL2," "Leopearl MKL2," "Leopearl TT2," and "Leopearl TL2" (manufactured by Chiba Flour Mills Co., Ltd.).

The inulin fatty acid ester is, for example, an ester of inulin and a fatty acid or a fatty acid derivative, and is preferably an ester of inulin and a linear or branched, saturated or unsaturated fatty acid having 8 to 32 carbon atoms, and the average molecular weight of the inulin is preferably 300 to 10,000. The inulin fatty acid ester may be a synthetic product or a commercially available product. Specifically, examples of the inulin fatty acid ester include those described in JP-A-3-197409 and JP-A-2002-193732, and examples of commercially available products include "Leopearl ISK2" (manufactured by Chiba Flour Mills Co., Ltd.).

Examples of the amino acid oil gelling agent include dibutyl lauroyl glutamide, dibutyl ethylhexanoyl glutamide, etc. The amino acid oil gelling agent may be a synthetic product or a commercially available product. Examples of commercially available amino acid oil gelling agents include "Amino Acid Oil Gelling Agent GP-1" and "Amino Acid Oil Gelling Agent EB-21" (manufactured by Ajinomoto Co., Inc.).

The gelling agent may be used, for example, alone or in combination with multiple types.

When the second composition of the present disclosure contains the gelling agent, the content of the gelling agent is, for example, 0.5% by mass or more, preferably 1% by mass or more, and more preferably 1.5% by mass or more, based on the total mass of the second composition. In addition, the content of the gelling agent is, for example, 50% by mass or less, preferably 45% by mass or less, and more preferably 40% by mass or less, in order to prevent the second composition from becoming too hard.

The second composition of the present disclosure may further contain a surfactant. The same explanation as for the first composition of the present disclosure may be used for the surfactant. When the second composition is an oil gel composition as described below, the surfactant can improve the feel of the second composition when applied and the solubility of the added components when, for example, oil gel particles as described below are blended into a water-based cosmetic product.

When the second composition of the present disclosure contains the surfactant, the content of the surfactant is, for example, 0.01% by mass or more, preferably 0.1% by mass or more, and more preferably 1% by mass or more, based on the total mass of the second composition of the present disclosure. Also, the content of the surfactant is 5% by mass or less, preferably 4% by mass or less, preferably 3% by mass or less, and more preferably 2% by mass or less.

When the second composition of the present disclosure contains the surfactant, the combined HLB value of the oil and the surfactant is preferably 8.5 or less. The HLB value is a value that indicates the degree of hydrophilicity or lipophilicity (hydrophobicity) of the surfactant, and means the HLB value at 25°C as defined by Griffin. The HLB value according to Griffin is defined in J. Soc. Cosm. Chem., 1954, 5:249-256. In addition, the concepts of organic value and inorganic value of oil in the organic conceptual diagram are highly correlated with the concepts of hydrophilicity and lipophilicity in the HLB method, and when the value calculated from the ratio of organic value to inorganic value: IV/OV = IOB (Inorganic Organic Balance) is compared with the HLB value, it is approximately determined that the HLB value = IOB value x 10.

In the present disclosure, the "mixed HLB value" refers to the HLB value of a mixture of one or more types of oils and one or more types of surfactants when the oils and surfactants are used. The mixed HLB value is a weighted average of the HLB values of each oil and each surfactant based on their mass ratio, and is calculated by the following formula (1).

Mixed HLB value = Σ (10 × IOBx × Wx) / Σ Wx (HLBy × Wy) / Σ Wy ... (1)
IOBx: IOB value of oil X Wx: mass of oil X (g)
HLBy: HLB value of surfactant Y Wy: mass (g) of surfactant Y

The mixed HLB value may be, for example, 0, but from the viewpoint of making the oil gel particles described below more compatible with water when used in aqueous cosmetic formulations, it is preferable that the mixed HLB value is greater than 0, more preferably 0.1 or more, and even more preferably 0.15 or more. In addition, since the second composition of the present disclosure can form particles without emulsification, the mixed HLB value is preferably 8.5 or less, more preferably 8.4 or less, and even more preferably 8.3 or less.

The second composition of the present disclosure may further include a dispersion medium. The dispersion medium may be, for example, an aqueous solvent. The aqueous solvent may be, for example, purified water, distilled water, ion-exchanged water, pure water, ultrapure water, etc.

When the second composition of the present disclosure contains the dispersion medium, the amount of the dispersion medium is not particularly limited and can be the remainder of the other components of the second composition. The amount of the dispersion medium is preferably, for example, 50 to 80% by mass based on the total mass of the second composition of the present disclosure.

The second composition of the present disclosure includes, for example, particles, and the particles preferably include the bactiol and the carotenoid. The shape of the particles is preferably, for example, spherical. The spherical shape may be a perfect sphere or a sphere with an elliptical cross section, with a perfect sphere being preferred. When the second composition of the present disclosure includes a gelling agent and forms particles, the particles can also be called oil gel particles. By forming the second composition of the present disclosure as the oil gel particles, the second composition can be applied as a skin agent without waste to areas where skin problems such as rough skin, dullness, and blemishes are observed.

The lower limit of the average particle size of the particles is preferably 100 μm or more, more preferably 125 μm or more, even more preferably 150 μm or more, and even more preferably 175 μm or more. The upper limit of the average particle size of the particles is, for example, 2000 μm or less, preferably 1500 μm or less, and more preferably 1000 μm or less. The average particle size of the particles can be measured, for example, by a sieve method. For example, the sieve method can be performed by using sieves with various mesh sizes to wet classify 100 g of the particles in water, remove excess water with filter paper, measure the mass, and measure the weight average particle size as the average particle size.

The compressive breaking strength of the particles is preferably, for example, 50 kPa or less from the viewpoint of improving the feel during use. The compressive breaking strength of the particles is preferably 0.15 kPa or more, more preferably 0.20 kPa or more, and even more preferably 0.25 kPa or more. In addition, from the viewpoint of good spreadability and compatibility on the skin when applied to the skin and enabling the particles to disintegrate smoothly, the compressive breaking strength of the particles is more preferably 40 kPa or less, and even more preferably 30 kPa or less. The compressive breaking strength means the maximum stress at which the gel sample breaks when a compressive load is applied to the gel sample. The compressive breaking strength can be expressed as the value (kPa (N/m ² )) obtained by dividing the compressive force when a uniaxial load is applied to a spherical gel sample by the cross-sectional area perpendicular to the axis. The compressive breaking strength is also called the compressive breaking stress, and can be measured by a known method using a known measuring device. The compressive breaking strength measuring device may be, for example, a compression tester (Rheo Meter: CR-3000EX) manufactured by Sun Scientific Co., Ltd.

The thermal stability of the carotenoid can be evaluated, for example, by using the presence rate (recovery rate) of the carotenoid in the target composition before and after heat treatment as an evaluation index. Specifically, the second composition of the present disclosure is heat-treated at 110°C for 30 minutes, and the carotenoid contained in the second composition of the present disclosure after the heat treatment is quantified. As a control group, a composition prepared in the same manner as the second composition of the present disclosure except that bactiol is not added is heat-treated at 110°C for 30 minutes, and the composition of the control group after the heat treatment is quantified. After the quantification, it can be evaluated based on whether the presence rate (recovery rate) of the carotenoid in the target composition has increased compared to the control group. In the evaluation, the presence rate (recovery rate) of the carotenoid in the second composition of the present disclosure after the heat treatment is 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more based on the presence rate (recovery rate) in the second composition of the present disclosure when bactiol is not contained in the second composition of the present disclosure. When the presence rate (recovery rate) of the carotenoid in the second composition of the present disclosure after the heat treatment is 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more, the thermal stability of the carotenoid in the target composition can be evaluated as being improved. The quantification of the carotenoid can be performed, for example, by absorbance measurement. The absorbance measurement can be performed, for example, by the method described in Japanese Patent No. 6575987. The quantification of the carotenoid may be performed immediately after the heat treatment, or may be performed 10 days after the heat treatment. When the carotenoid is a retinoid, the thermal stability of the retinoid can be evaluated, for example, by quantifying vitamin A, specifically, using Vitamin A Quantitation Method 1-1, etc.

The second composition of the present disclosure can also be referred to as, for example, an oil gel composition or an oily solid composition.

The second composition of the present disclosure can be produced, for example, by mixing the bactiol and the carotenoid. The bactiol is usually in a liquid state. Therefore, the second composition can be produced, for example, by adding the carotenoid to the bactiol and then mixing. The mixture is preferably prepared, for example, by mixing the bactiol and the carotenoid and homogenizing or dispersing them in the dispersion medium. The mixing can be performed, for example, by manual shaking, stirring using a stirrer or a stirring blade, or using an ultrasonic vibrator. The mixing temperature is not particularly limited as long as it is a temperature at which the mixture of the bactiol and the carotenoid can be mixed, preferably a temperature at which they can be mixed uniformly, and is preferably 20 to 30°C, and more preferably 23 to 25°C, for example. The mixing time is not particularly limited as long as it is a time at which the mixture can be mixed uniformly, and is preferably 5 minutes to 1 hour, for example.

When the second composition is an oil gel composition, the method for producing the second composition can refer to, for example, the method described in Example 2. When the second composition is an oil gel composition, the mixture may contain, for example, an oil agent and/or a gelling agent. When the mixture contains the oil agent and/or gelling agent, the oil agent and/or gelling agent may be prepared by mixing the oil agent and the gelling agent, or the oil agent alone or the gelling agent alone may be added. When the mixture contains the oil agent and/or gelling agent, the oil agent and/or gelling agent may be included during the preparation of the mixture, or may be included before or after the preparation of the mixture.

When the second composition is an oil gel composition, the method for producing the second composition preferably includes, for example, subjecting the mixture to a heat treatment (heating treatment) after the mixing. This allows the bactiol and the carotenoid to be uniformly dispersed in the oil gel composition in the method for producing the second composition. The heating temperature is, for example, 80 to 130°C, and preferably about 110°C. The heating time is, for example, 10 minutes to 2 hours, and preferably about 30 minutes. The method for producing the second composition may include, for example, cooling the heat-treated mixture after the heat treatment. The cooling is, for example, preferably performed by cooling the mixture to a temperature of 20 to 30°C, and more preferably to 23 to 25°C.

The method for producing the second composition may, for example, add the heat-treated mixture to a dispersion medium such as the water-soluble solvent as a dispersion liquid after the heat treatment. In this way, the method for producing the second composition may, for example, cause the oil gel composition to form particles, and produce the oil gel particles. The addition is preferably performed under stirring. The temperature during the stirring is not particularly limited, for example, as long as the mixture can form particles in the dispersion medium, and is preferably 10 to 60°C, for example. The time during the stirring is not particularly limited, for example, as long as the mixture can form particles in the dispersion medium, and is preferably 1 to 15 minutes, and more preferably 3 to 5 minutes, for example.

The dispersion medium may contain other components, such as a surfactant, a dispersant such as concentrated glycerin, etc. When the dispersion medium contains the other components, the method for producing the second composition includes, for example, mixing the dispersion medium with the surfactant and/or the dispersant before, during, or after the addition of the mixture, and homogenizing or dispersing in the dispersion medium. The temperature during the mixing is not particularly limited as long as the surfactant and/or the dispersant can be dispersed in the dispersion medium, and as an example, 20 to 30°C is preferable. The time during the mixing is not particularly limited as long as the surfactant and/or the dispersant can be dispersed in the dispersion medium, and as an example, 10 minutes to 2 hours is preferable.

After forming particles from the mixture, the method for producing the second composition may, for example, include sieving. This allows the method for producing the second composition to adjust the particle size of the oil gel particles and improve the feel during use. The sieving can be performed, for example, using a sieve.

After the sieving, the method for producing the second composition may, for example, wash the oil gel particles. The washing can be carried out, for example, by a known method, specifically, washing with an aqueous solvent. Examples of the aqueous solvent include purified water, distilled water, ion-exchanged water, pure water, and ultrapure water.

After the washing, the method for producing the second composition may, for example, dry the oil gel particles. The drying may be carried out by a known method, for example, by drying at room temperature by leaving the particles to stand, freeze drying, spray drying, etc.

<Third Composition>
In another aspect, the present disclosure provides a composition (hereinafter also referred to as "third composition") with improved permeability of bactiol through the stratum corneum. As described above, the third composition of the present disclosure includes liposomes, and the liposomes include bactiol, complex lipids, and sterols. The third composition of the present disclosure includes liposomes, and the liposomes include bactiol, complex lipids, and sterols, and other configurations and conditions are not particularly limited. According to the third composition of the present disclosure, for example, a composition with improved permeability of bactiol through the stratum corneum can be provided. The third composition of the present disclosure can be described by using the explanation of the first composition of the present disclosure and the second composition of the present disclosure.

As a result of extensive research, the inventors have discovered that by forming liposomes with bactiol, complex lipids and sterols, the permeability through the stratum corneum is higher than that of bactiol alone, and have established the present disclosure. It is presumed that the improvement in the permeability through the stratum corneum is due to the improved dispersibility of the bactiol within the stratum corneum as a result of the formation of the liposome. However, this presumption does not limit the present disclosure in any way. Therefore, according to the present disclosure, it is possible to provide a composition in which the permeability through the stratum corneum of bactiol is improved.

The content of the bactiol is preferably, for example, greater than 0% by mass to 40% by mass, 2 to 40% by mass, 4 to 40% by mass, 4 to 25% by mass, 5 to 40% by mass, 5 to 25% by mass, or 5 to 10% by mass, based on the total mass of the liposome.

The complex lipid is a lipid containing phosphoric acid, sugar, sulfur, or a nitrogen-containing base in the molecule. The complex lipid is not particularly limited, and examples thereof include phospholipids, glycolipids, lipoproteins, and sulfolipids, and is preferably a phospholipid. The phospholipid is not particularly limited as long as it is a lipid having a phosphate ester moiety in the molecular structure and is capable of forming a bilayer membrane. Examples of the phospholipid include phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, and phosphatidic acid, and is preferably phosphatidylcholine.

The content of the complex lipid is preferably, for example, 25 to 75 mass%, 30 to 60 mass%, or 40 to 45 mass% based on the total mass of the liposome.

The sterols include, for example, plant sterols (phytosterols) and animal sterols (zoosterols). The animal sterols include, for example, cholesterol; cholesterol derivatives such as dihydrocholesterol, dehydrocholesterol, cholesteryl oleate, cholesteryl isostearate, cholesteryl hydroxystearate, and polyoxyethylene cholesteryl ether; and the like; preferably, cholesterol.

The content of the sterols is preferably, for example, 2 to 20% by mass, 5 to 15% by mass, or 8 to 10% by mass based on the total mass of the liposome.

The liposome may further contain, for example, an anionic substance. The anionic substance refers to a substance that is negatively charged when dissolved in water. Examples of the anionic substance include diacylglycerol hemisuccinate, diacylglycerol hemimalonate, diacylglycerol hemiglutarate, diacylglycerol hemiadipate, diacylglycerol hemicyclohexane-1,4-dicarboxylic acid, and fatty acids. Examples of the fatty acids include oleic acid, myristic acid, palmitic acid, stearic acid, nervonic acid, and behenic acid. The anionic substance is preferably, for example, a saturated fatty acid that is solid at room temperature (10°C to 30°C), and is preferably palmitic acid, stearic acid, or the like.

When the third composition of the present disclosure contains the anionic substance, the content of the anionic substance is, for example, preferably from more than 0% to 20% by mass, 1 to 18% by mass, or 2 to 16% by mass, and more preferably 2.5 to 15% by mass, based on the total mass of the liposomes. By setting the content of the anionic substance to 20% by mass or less, the third composition of the present disclosure can favorably maintain the emulsified state of the liposomes in the aqueous solvent and can suppress the occurrence of turbidity, aggregation, or precipitation.

The liposome may further contain, for example, a zwitterionic surfactant. Examples of the zwitterionic surfactant include N-alkyl-N,N-dimethylamino acid betaines including lauryl dimethylamino acetate betaine (lauryl betaine); fatty acid amidoalkyl-N,N-dimethylamino acid betaines including cocamidopropyl betaine and lauramidopropyl betaine; imidazoline-type betaines including sodium cocoamphoacetate and sodium lauroamphoacetate; alkyl sulfobetaines including alkyl dimethyl taurine; sulfate-type betaines including alkyl dimethyl amino ethanol sulfate; and phosphate-type betaines including alkyl dimethyl amino ethanol phosphate.

When the third composition of the present disclosure contains the zwitterionic surfactant, the content of the zwitterionic surfactant is, for example, preferably 0 to 20 mass%, more preferably 5 to 20 mass%, or 7 to 15 mass%, based on the total mass of the liposomes. By setting the content of the zwitterionic surfactant to 20 mass% or less, for example, the third composition of the present disclosure can favorably maintain the emulsified state of the liposomes in the aqueous solvent and can suppress the occurrence of turbidity, aggregation, or precipitation.

The liposome is preferably a pH-responsive liposome. In the present disclosure, the term "pH-responsive" means, for example, that the zeta potential of the liposome changes from positive to negative under any pH condition within a predetermined range. Specifically, when dispersed in an aqueous medium with a pH of 5 or less, the zeta potential of the liposome is positive, when dispersed in an aqueous medium with a pH of 8 or more, the zeta potential of the liposome is negative, and when dispersed in an aqueous medium with a pH of 5 to 8, the zeta potential of the liposome changes from positive to negative with an increase in the pH value. For this reason, it is considered that the liposome contained in the third composition of the present disclosure retains bactiol and exists stably in an aqueous medium with a pH of 5 or less, and becomes unstable under pH conditions in an aqueous medium with a pH of 5 to 8 where the zeta potential becomes zero, causing membrane fusion and releasing bactiol. The zeta potential can be measured by a known method. Specific examples of the method for measuring the zeta potential include electrophoretic light scattering measurement (laser Doppler method) and the like.

The shape of the liposome is not particularly limited, and may be a multilayer liposome or a single-layer liposome.

The average particle size of the liposomes is preferably 50 to 1100 nm, 50 to 200 nm, or 50 to 100 nm. The average particle size of the liposomes can be measured by known methods, such as dynamic light scattering. The average particle size of the liposomes can be adjusted appropriately depending on the application. For example, when the liposomes are intended for administration to the body, the particle size of the liposomes is preferably adjusted to an average particle size of 200 nm or less. The average particle size of the liposomes can be adjusted, for example, by passing the liposomes through a filter with a small pore size using an extruder or the like. When the average particle size of the liposomes is about 100 nm or less and the liposomes are unilamellar liposomes, the liposomes are, for example, uniform in size and thermodynamically stable, and have good skin permeability when used as a cosmetic.

The permeability of the third composition of the present disclosure to the stratum corneum can be evaluated, for example, by the permeability of the third composition of the present disclosure using an artificial synthetic membrane such as a membrane for skin permeability testing. Specifically, see Example 3 described below. When an absorption test is performed using a Franz cell and a Strat-M (trademark) membrane, if the increase in the amount of bactiol absorbed is 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more compared to the case of bactiol-containing water and/or the case of only the membrane agent component, it can be determined that the third composition of the present disclosure has improved permeability to the stratum corneum.

The method for producing the third composition of the present disclosure can be, for example, produced in accordance with the method for producing liposomes, and for example, the method for producing liposomes in International Publication No. 2019/045097 can be referenced. The method for producing the third composition may refer to the method described in Example 3 below. As an example, the method for producing the third composition can be prepared by mixing a dispersion medium (first preparation liquid) such as an aqueous solvent containing bactiol with a dispersion medium (second preparation liquid) containing a component that constitutes the lipid membrane of the liposome.

The first preparation liquid can be prepared, for example, by dispersing the bactiol in a dispersion medium such as the aqueous solvent. The dispersion can be performed by mixing the bactiol with the dispersion medium. The first preparation liquid may further contain, for example, a preservative, a solubilizer, etc. Examples of the preservative include phenoxyethanol, etc. Examples of the solubilizer include nonionic surfactants such as polysorbate 60. The temperature in the dispersion is not particularly limited as long as the bactiol can be dispersed in the dispersion medium, and is preferably, for example, 70 to 90°C, and more preferably, 75°C to 85°C. The time in the dispersion is not particularly limited as long as the bactiol can be dispersed in the dispersion medium, and is preferably 3 minutes to 1 hour, and more preferably, 5 minutes to 30 minutes, and more preferably, 10 minutes.

Next, the second preparation liquid is preferably prepared by mixing the components constituting the lipid membrane of the liposome, such as the complex lipid and the sterols, with a dispersion medium such as an organic solvent, and homogenizing or dispersing the components in the dispersion medium. Examples of the organic solvent include polyhydric alcohols such as butylene glycol, glycerin, and concentrated glycerin. The mixing is preferably performed by stirring without foaming. The mixing temperature is not particularly limited, for example, as long as the components constituting the lipid membrane can be dispersed in the dispersion medium. For example, 70 to 90°C is preferable, and 75 to 85°C is more preferable. The mixing time is not particularly limited, for example, as long as the components constituting the lipid membrane can be dispersed in the dispersion medium. For example, 15 minutes to 1 hour, and 30 minutes is preferable.

The second preparation liquid may further contain, for example, the anionic substance, the zwitterionic surfactant, etc.

After mixing the complex lipids and the sterols, the second preparation liquid may be prepared by adding the mixture of the complex lipids and the sterols to a dispersant (dispersion medium) such as concentrated glycerin, and mixing and homogenizing the mixture. The method for producing the third composition disperses the complex lipids and the sterols in the dispersion medium multiple times, thereby efficiently forming the liposomes when mixed with the first preparation liquid. The dispersant is preferably used at 80 to 85°C.

The method for producing the third composition includes, for example, mixing the first preparation liquid and the second preparation liquid. The mixing temperature is not particularly limited as long as it is a temperature at which the first preparation liquid and the second preparation liquid can be mixed, and as an example, 75 to 90°C is preferable. The mixing time is not particularly limited as long as it is a time at which the first preparation liquid and the second preparation liquid can be mixed, and as an example, 15 minutes to 1 hour, and 30 minutes is preferable.

<Fourth Composition>
In another aspect, the present disclosure provides a powder composition containing bactiol (hereinafter also referred to as "fourth composition"). As described above, the fourth composition of the present disclosure contains bactiol and silica, and the bactiol is supported on the silica. The fourth composition of the present disclosure is characterized in that it contains bactiol and silica, and the bactiol is supported on the silica, and other configurations and conditions are not particularly limited. According to the fourth composition of the present disclosure, for example, bactiol can be provided in powder form. The fourth composition of the present disclosure can be described in the first, second, and third compositions of the present disclosure.

As a result of intensive research, the inventors discovered that silica can support bactiol, and that liquid bactiol can be converted into powder form, leading to the establishment of the present disclosure. Therefore, according to the present disclosure, it is possible to provide a composition containing bactiol that is easy to handle.

The content of the bactiol is preferably, for example, 0.01 to 30 mass%, 0.1 to 20 mass%, or 1 to 10 mass% based on the total mass of the fourth composition of the present disclosure.

The silica is not particularly limited, and can be, for example, silica used in ordinary skin external preparations, cosmetics, etc., specific examples include silicic anhydride, silicon dioxide, etc. The particle shape of the silica is not particularly limited, and can be any shape, but spherical is preferable because it can be used suitably in cosmetics. The silica can be, for example, porous silica, hollow silica, nonporous silica, etc., and porous silica is preferable because it has an excellent capacity to support bactiol. The silica can be used alone or in combination of multiple types. The silica can be a synthetic product or a commercially available product. The silica can be used with the surface untreated, or can be used after various treatments.

The content of the silica is preferably 60 to 95 mass%, 70 to 90 mass%, or 75 to 85 mass% based on the total mass of the fourth composition of the present disclosure, for example, because this provides excellent handling properties.

The average particle size of the fourth composition of the present disclosure is preferably 0.01 to 500 μm, 0.1 to 100 μm, 1 to 10 μm, or 4 to 6 μm, since it can be suitably used in cosmetics, for example. The average particle size can be measured by observing the silica carrying bactiol using a transmission electron microscope (TEM). The average particle size can also be referred to as the average particle size of the silica carrying bactiol.

Examples of the higher alcohol include behenyl alcohol, cetyl alcohol, stearyl alcohol, myristyl alcohol, cetostearyl alcohol, isostearyl alcohol, monostearyl glycerin ether (batyl alcohol), lauryl alcohol, hexadecyl alcohol, octyldodecanol, oleyl alcohol, 2-decyltetradecinol, lanolin alcohol, etc. The higher alcohol is preferably behenyl alcohol, since it can impart a feeling of use such as a smooth feel.

When the fourth composition of the present disclosure contains the higher alcohol, the content of the higher alcohol is preferably, for example, greater than 0% by mass to 30% by mass based on the total mass of the fourth composition of the present disclosure.

The bactiol is, for example, supported on at least one of the surface and the interior of the silica. It is preferable that the bactiol is supported at least inside the porous silica.

The fourth composition of the present disclosure can be produced, for example, by contacting the bactiol with the silica, specifically by mixing the bactiol with the silica. For the production method of the fourth composition, the method described in Example 4 can be referenced.

The mixing can be performed, for example, by manual shaking, stirring with a stirrer or a stirring blade, or by using an ultrasonic vibrator. The mixing temperature is preferably, for example, 40 to 70°C. The mixing time is preferably 0.5 to 1.5 hours.

Prior to the mixing, the bactiol is preferably dispersed in a solvent such as ethanol. In this way, the fourth method for producing the composition can increase the amount of bactiol supported on the silica, for example, by uniformly impregnating the silica with the bactiol during the mixing.

After the mixing, the method for producing the fourth composition preferably includes, for example, mixing the resulting mixture with a higher alcohol. By mixing the higher alcohol, the method for producing the fourth composition can impart a texture such as a smooth feel to the resulting fourth composition. After mixing with the higher alcohol, the method for producing the fourth composition may include, for example, heating and stirring. The temperature during the heating and stirring is preferably, for example, 100 to 110°C, and more preferably 105°C. The time period during the heating and stirring is preferably, for example, 0.5 to 1.5 hours, and more preferably 1 hour.

After the heating and stirring, the fourth composition production method preferably includes, for example, cooling the mixture after the heating and stirring. The cooling is preferably performed, for example, to 40 to 60°C.

After cooling, the fourth composition manufacturing method may include sieving, for example, to remove foreign matter or adjust the particle size of the bactiol-loaded silica. The sieving can be performed, for example, using a sieve.

<Use>
The conditions for use (administration conditions) of the first to fourth compositions of the present disclosure are not particularly limited, and the administration form, administration time, administration amount, etc. can be appropriately set depending on, for example, the type of subject to be administered.

The preferred administration form for the first to fourth compositions of the present disclosure is parenteral administration. Examples of parenteral administration include transdermal administration and application (contact) to the skin. Application to the skin may include application to the oral mucosa, i.e., application to or contact with epithelial cells in the oral cavity. Application to the skin may also include administration or injection into the skin or subcutaneously via the skin surface, in addition to or instead of application to the skin surface. Administration or injection into the skin via the skin surface can be performed, for example, using a microneedle.

When the first to fourth compositions of the present disclosure are used for transdermal administration or application to the skin (hereinafter also referred to as "topical skin preparations"), the form of the topical skin preparation may be, depending on the form of use, an ampoule, capsule, powder, granule, liquid, gel, foam, emulsion, sheet, mist, spray, etc. Examples of the form of use include pharmaceutical product(s); quasi-drug product(s); topical skin preparations for local or whole body use; medicinal and/or cosmetic preparations to be applied to the scalp and hair; bath additives to be added to bath water; other preparations; etc. Examples of the topical or systemic skin preparations include basic cosmetics such as lotions, milky lotions, creams, ointments, lotions, oils and packs; face washes or skin cleansers such as solid soap, liquid soap and hand wash; massage preparations, cleansing preparations, hair removal preparations, depilatories, shaving treatments, aftershave lotions, pre-shave lotions, shaving creams, makeup cosmetics such as foundations, lipsticks, blushers, eye shadows, eyeliners and mascaras; perfumes, nail beautifying preparations, nail beautifying enamel, nail beautifying enamel removers, poultices, plasters, tapes, sheets, patches, aerosols, toothpastes and mouthwashes. Examples of medicinal and/or cosmetic preparations to be applied to the scalp and hair include shampoos, rinses, hair treatments, pre-hair treatments, permanent solutions, hair dyes, hair styling products, hair tonics, hair growth and care products, poultices, plasters, tapes, sheets, aerosols, etc. Examples of other preparations include underarm odor prevention or deodorants, antiperspirants, sanitary products, sanitary cotton, wet tissues, etc.

Next, examples of the present invention will be described. However, the present invention is not limited to the following examples. Commercially available reagents were used according to their protocols unless otherwise specified.

[Example 1]
A first composition of the present disclosure was prepared, and its dispersibility in a solvent was confirmed.

[Example 1A]
The first composition was prepared by combining various components shown in Table 1 below and by the following method. 0.02 parts (parts by mass, hereinafter the same) of bactiol (manufactured by Ichimaru Pharcos Co., Ltd.) and 0.98 parts of tri(caprylic acid/capric acid)glyceryl (solvent, manufactured by Kokyu Alcohol Kogyo Co., Ltd. or Nisshin Oillio Group Co., Ltd.) were mixed. After the mixing, 0.4 parts of phenoxyethanol (preservative, manufactured by Yokkaichi Synthetic Co., Ltd. or Toho Chemical Industry Co., Ltd.) and 2.0 parts of PPG-6 decyltetradeceth-30 (nonionic surfactant, manufactured by Nippon Chemicals Sales Co., Ltd.) were added to the resulting mixture, and homogenization was performed under conditions of 60 to 70°C to obtain mixture I. Next, 0.1 parts of oligopeptide-56 amide PEG-75 methyl ether (block copolymer, manufactured by Ichimaru Pharcos Co., Ltd.) and 48.25 parts of purified water were mixed. After the mixing, nanoparticle processing (50 MPa, 1 pass) was performed to obtain mixture II. Thereafter, mixture II heated to 60-70°C was added to 48.25 parts of purified water heated to 60-70°C, and homogenization was performed to obtain mixture III. Mixture I was added to mixture III, and stirring was performed. After stirring, the mixture was cooled. After cooling, purified water was added so that the total amount became 100 parts, and homogenization was performed to obtain the composition of Example 1A.

[Example 1B]
The composition of Example 1B was obtained in the same manner as in Example 1A, except that 0.08 parts of bactiol and 0.92 parts of caprylic/capric triglyceride were used.

[Example 1C]
The composition of Example 1C was obtained in the same manner as in Example 1A, except that 0.16 parts of bactiol and 0.84 parts of caprylic/capric triglyceride were used.

[Example 1D]
The composition of Example 1D was obtained in the same manner as in Example 1A, except that 0.2 parts of bactiol and 0.8 parts of caprylic/capric triglyceride were used.

[Example 1E]
The various components shown in Table 2 below were combined to prepare the first composition of the present disclosure by the following method. 0.3 parts of bactiol (manufactured by Ichimaru Pharcos Co., Ltd.) and 1.0 parts of tri(caprylic acid/capric acid)glyceryl (solvent, manufactured by Kokyu Alcohol Kogyo Co., Ltd. or Nisshin Oillio Group Co., Ltd.) were mixed. After the mixing, 0.4 parts of phenoxyethanol (preservative, manufactured by Yokkaichi Synthetic Co., Ltd. or Toho Chemical Industry Co., Ltd.), 2.0 parts of PPG-6 decyltetradeceth-30 (nonionic surfactant, manufactured by Nippon Chemicals Co., Ltd.), 2.0 parts of BG (solvent, butylene glycol, manufactured by Daicel Corporation, Nippon Refine Co., Ltd., or Kokyu Alcohol Kogyo Co., Ltd.), and 0.1 parts of oligopeptide-56 amide PEG-75 methyl ether (block copolymer, manufactured by Ichimaru Pharcos Co., Ltd.) were added, and the mixture was homogenized under conditions of 60 to 70°C to obtain mixture I. Thereafter, mixture I heated to 60 to 70°C was added to 94.2 parts of purified water heated to 60 to 70°C, and homogenized to obtain mixture II. Mixture II was subjected to nanoparticle formation treatment (50 MPa, 1 pass), and purified water was added to make the total amount 100 parts, and homogenized to obtain the composition of Example 1E.

[Example 1F]
The composition of Example 1F was obtained in the same manner as in Example 1E, except that 0.5 parts of bactiol and 94.0 parts of purified water were used.

[Example 1G]
The composition of Example 1G was obtained in the same manner as in Example 1E, except that 0.5 parts of bactiol, 3 parts of BG, and 93.0 parts of purified water were used.

[Example 1H]
The composition of Example 1H was obtained in the same manner as in Example 1E, except that 0.5 parts of bactiol, 3 parts of BG, and 2.5 parts of PPG-6 decyltetradeceth-30 were used, and the nanoparticle formation treatment was performed in 3 passes.

The compositions of Examples 1A to 1H are shown in Table 3 below.

[Test Example 1] Dispersibility The dispersibility of each of the compositions of Examples 1A to 1H in a solvent was examined. Specifically, the compositions of Examples 1A to 1H were left to stand under the conditions of 25°C for one month in the dark. The results are shown in FIG.

Figure 1 is a photograph showing the dispersibility of each of the first compositions of the present disclosure in a solvent. As shown in Figure 1, no precipitation was observed in the compositions of Examples 1A to 1H. These results show that the particles of the first composition of the present disclosure are uniformly distributed in the solvent without agglomeration, i.e., the composition has dispersibility in the solvent.

[Test Example 2] Average particle size Next, the average particle size of the oil droplets formed in the first composition of the present disclosure was measured for the first composition of the present disclosure. Specifically, the composition of Example 1B, 1E, or 1H was left standing under the condition of 25°C for one month under the condition of being shielded from light. After the standing, it was diluted 100 times with ultrapure water. After the dilution, the average particle size distribution was measured using a Zetasizer Nano (manufactured by Malvern Panalytical). In addition, in the measurement, calibration was performed using standard particles. In addition, the measurement is a measurement based on the measurement principle of dynamic light scattering. These results are shown in FIG. 2.

Figure 2 is a graph showing the distribution of the average particle size of the oil droplets contained in each of the first compositions of the present disclosure. In Figure 2, the vertical axis shows scattering intensity (%) and the horizontal axis shows average particle size (nm). As shown in Figure 2, at a bactiol concentration of 0.08% (composition of Example 1B), the average particle size was 26.8 nm. At a bactiol concentration of 0.3% (composition of Example 1E), the average particle size was 25.9 nm. At a bactiol concentration of 0.5% (composition of Example 1H), the average particle size was 49.5 nm.

[Example 2]

The thermal stability of the carotenoid in the second composition of the present disclosure was confirmed.

(1) Preparation of the second composition The second composition of the present disclosure was prepared by combining the various components listed in Table 4 below, by the following method. 49.32 g of NIKKOL sugar squalane (oil agent, manufactured by Nikko Chemicals Co., Ltd.), 21.6 g of palmitic acid dextrin (gelling agent, Leopard KL2, manufactured by Chiba Flour Milling Co., Ltd.), 0.72 g of vitamin A palmitate (carotenoid derivative, unstable, manufactured by BASF Japan Co., Ltd.), and 0.36 g of bactiol (manufactured by Ichimaru Pharcos Co., Ltd.) were stirred under room temperature (about 24°C. The same applies below). After the stirring, it was confirmed that each component was uniformly dispersed in the oil agent. After the confirmation, the mixture was heated to 110°C and held for 30 minutes for heat treatment, thereby obtaining a mixture I. Next, 200 g of concentrated glycerin for cosmetics (dispersant, manufactured by Iwaki Co., Ltd.), 120 g of purified water (dispersion medium), and 10.24 g of EMALEX ET-8020 (surfactant, manufactured by Nippon Emulsion Co., Ltd.) were stirred to obtain a mixture II. Then, while stirring the mixture II, the mixture I was added and stirred for 4 minutes. After the stirring, the formation of particles was confirmed. After the confirmation, sieving was performed using a sieve with an opening size of 1.5 mm. After the sieving, the sieve was washed with water and dried for 2 days. After the drying, the composition of Example 2 was obtained. A part of the composition of Example 2 was further stored under a condition of 25°C for about 10 days under a light-shielded condition.

The component contents and composition of the composition of Example 2 are shown in Table 5 below.

(2) Evaluation of Thermal Stability of Retinol Palmitate Next, the thermal stability of vitamin A palmitate contained in the composition of Example 2 was examined. Specifically, the thermal stability was evaluated based on Vitamin A Quantitative Method 1-1 described in Quasi-Drug Raw Materials Standard 2021 (Pharmaceutical and Food Safety Bureau, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labor and Welfare). First, 2-propanol was added to the second composition of the present disclosure and stirred. After the stirring, ultrasonic disruption was performed and centrifugation was performed. After the centrifugation, the supernatant was separated. After the separation, 2-propanol was added to the obtained supernatant, and the above-mentioned operation was repeated twice. After the final separation of the supernatant, 2-propanol was added to the obtained supernatant to prepare an appropriate concentration, and the mixture was subjected to Vitamin A Quantitative Method 1-1. The appropriate concentration was adjusted so that the absorbance at the measurement wavelength was between 0.1 and 1. The absorption spectrum of the sample after the concentration adjustment was measured in the wavelength range of 220 to 400 nm, and the wavelength of the absorption maximum was determined. Next, the absorbance of the sample was measured at wavelengths of 300 nm, 310 nm, 320 nm, 330 nm, 340 nm, and 350 nm. When the ratio (Aλ _i /A ₃₂₆ ) of the absorbance at each wavelength (Aλ _i ) to the absorbance at a wavelength of 326 nm (A ₃₂₆ ) was within the range of ±0.030 of the values shown in Table 6 below, the vitamin A concentration in the sample was calculated using the following formula (2). Note that when the absorption maximum wavelength is outside the range of 325 to 328 nm, or when the absorbance ratio (Aλ _i /A ₃₂₆ ) is outside the range of ±0.030 of the values shown in Table 6 below, the vitamin A quantitative method 1-1 described in the Quasi-drug Raw Material Standards is not suitable. The absorbance ratio (Aλ _i /A ₃₂₆ ) of the second composition of the present disclosure was outside the range of ±0.030 of the values shown in Table 6 below. However, since the bactiol contained in the second composition of the present disclosure has an absorbance of almost zero at a wavelength of 326 nm, it was determined that the bactiol does not affect the calculated value of the following formula (2), and the second composition of the present disclosure was analyzed using Vitamin A Quantitative Method 1-1 described in the Quasi-Drug Raw Material Standards. As a blank, a composition prepared in the same manner as in Example 2 (1) was used, except that it did not contain vitamin A palmitate (retinol palmitate). Since the blank composition has an absorbance at a wavelength of 326 nm, it was used as a blank at a wavelength of 326 nm. As a comparative example, a composition prepared in the same manner as the composition of Example 2, except that bactiol was not added, was used. The content of vitamin A obtained relative to the amount of vitamin A used during production was calculated as the recovery rate. In addition, in calculating the recovery rate, the actual concentration immediately after dissolving vitamin A palmitate in 2-propanol was used as the standard. These results are shown in Table 7 below.

Number of vitamin A units in 1g = A ₃₂₆ x V x 1900 / (W x 100) ... (2)
A ₃₂₆ : Absorbance at a wavelength of 326 nm V: Volume (ml) of the prepared sample solution
W: Amount of sample (g) in V ml of sample solution
1900: Conversion factor of specific absorbance of esterified retinol into international units (units/g)

Table 7 shows the recovery rate of vitamin A based on the vitamin A concentration calculated using Vitamin A Quantitative Method 1-1 described in the Quasi-Drug Raw Materials Standards. As shown in Table 7, the recovery rate of retinol palmitate in the comparative example (-bakuchiol) was 2.8% immediately after production and 3.4% about 10 days after production. On the other hand, the recovery rate of retinol palmitate in the composition of Example 2 (+bakuchiol) was 57.6% immediately after production and 52.4% about 10 days after production. These results show that the thermal stability of retinol palmitate in the second composition of the present disclosure is improved.

[Example 3]
A third composition of the present disclosure was prepared, and its permeability to the stratum corneum was confirmed.

(1) Preparation of the third composition The third composition of the present disclosure was prepared by combining the various components and compositions shown in Table 8 below by the following method. 96.8 g of purified water (dispersion medium), 2 g of phenoxyethanol (preservative, HYSOLV EPH, manufactured by Toho Chemical Industry Co., Ltd.), 1 g of polysorbate 60 (solubilizer, EMALEX TS-10V, manufactured by Nippon Emulsion Co., Ltd.), and 0.19 g of bactiol (manufactured by Ichimaru Pharcos Co., Ltd.) were mixed and heated to 75 to 85°C to obtain solution I. Next, 2.05 g of hydrogenated phosphatidylcholine (complex lipid, Phospholipon 90H, H-Holstein Co., Ltd.), 0.45 g of cholesterol (sterol, Kairei Marine Cholesterol, Nippon Suisan Co., Ltd.), 0.25 g of palmitic acid (anionic substance, NAA-160, NOF Corporation), and 0.5 g of lauryl betaine (zwitterionic surfactant, NIKKOL AM-301, Nikko Chemicals Co., Ltd.) were added in this order to 48.375 g of 1,3-butylene glycol (solvent, butylene glycol, manufactured by Daicel Corporation, Nippon Refine Co., Ltd., or Kokyu Alcohol Kogyo Co., Ltd.) that had been heated to 75 to 85°C, and the mixture was stirred and dissolved without foaming, to obtain solution II. Then, the solution II was added to 48.375 g of concentrated glycerin (dispersant, concentrated glycerin for cosmetics, manufactured by Iwaki Co., Ltd.) that was being heated to 80 to 85°C and stirred, and homogenized to obtain solution III. After the homogenization, the solution I and the solution III were mixed under heating and allowed to cool, thereby obtaining the composition of Example 3.

(2) Evaluation of stratum corneum permeability Next, the stratum corneum permeability of the composition of Example 3 was examined. Specifically, a Strat-M (trademark) membrane was attached to a static diffusion cell (Franz cell). The Strat-M (trademark) has a structure similar to that of human skin, and is therefore generally used to evaluate the permeability to the stratum corneum. Physiological saline (0.9% sodium chloride water) was used as the receptor liquid on the reservoir side. In addition, 1.0 ml of the third composition of the present disclosure was used on the donor side. The entire Franz cell was kept at 32°C, and the membrane was collected after 3 hours or 24 hours. After the collection, the membrane was washed with purified water and dried. After the drying, the membrane was exposed to UV 254 nm and fluorescence observation was performed. In addition, after the drying, 20 ml of ethanol was added to each membrane. After the addition, the ethanol was collected, and the components were extracted from the filter again with 20 ml of ethanol, and the ethanol was collected. Then, ethanol was distilled off from the total 40 ml of ethanol collected, and bactiol was quantified. The quantification was carried out by HPLC analysis under the following measurement conditions. From the obtained quantification value, the recovery rate of bactiol was calculated based on the bactiol introduced into the static diffusion cell. Note that, as control 1, the same method was used except that 0.1% bactiol-containing water was used instead of the third composition of the present disclosure. Also, as control 2 (only membrane agent component), the same method was used except that the bactiol-free composition prepared by the method of Example 3 (1) using water instead of bactiol was used instead of the third composition of the present disclosure. These results are shown in Figure 3.

(HPLC measurement conditions)
HPLC system: SHIMADZU LC-20ADxr (manufactured by Shimadzu Corporation)
Column: Mightysil RP-18GP 250 x 4.6 mm (particle size 5 μm) (Kanto Chemical Co., Ltd.)
Flow rate: 1.0mL/min
Detector wavelength: 260 nm
Gradient program: _CH3CN :0.1% _H3PO4 = _80:20

Figure 3 is a photograph showing the stratum corneum permeability of the third composition of the present disclosure. Figure 3 (A) shows the results after 3 hours, and Figure 3 (B) shows the results after 24 hours. In Figure 3, the top row is a photograph of the front side of the Franz cell, and the bottom row is a photograph of the back side of the Franz cell. From the left, Figure 3 shows the results of the third composition of the present disclosure, Control 1, and Control 2 (film-forming component only). As shown in Figure 3, it was found that the third composition of the present disclosure had penetrated to the back side of Strat-M (trademark) after 24 hours, compared to Control 1 and Control 2.

Furthermore, the recovery rate of bactiol after 3 hours was 2.3% for the third composition of the present disclosure, 0.5% for control 1, and 0% for control 2. The recovery rate of bactiol after 24 hours was 8.9% for the third composition of the present disclosure, 2.4% for control 1, and 0% for control 2. These results demonstrate that the third composition of the present disclosure has high stratum corneum permeability.

[Example 4]
A fourth composition of the present disclosure was prepared and confirmed to have excellent handling properties.

The various components and compositions shown in Table 9 below were combined to prepare the fourth composition of the present disclosure by the following method. Specifically, 2.0 g of bactiol (manufactured by Ichimaru Pharcos Co., Ltd.) and 18 g of ethanol (solvent) were mixed. After the mixing, 16.0 g of silica (carrier, Sunsphere H-53, manufactured by AGC Si-Tech Co., Ltd.) was added and stirred and mixed. After the mixing, 2.0 g of behenyl alcohol (higher alcohol, Kalcol 220-80, manufactured by Kao Corporation) was added and mixed. After the mixing, the mixture was heated and stirred at 105°C for 1 hour. Then, the mixture was cooled to 40 to 60°C. After the cooling, foreign matter was removed using a 100-mesh sieve to obtain the composition of Example 4. The obtained composition of Example 4 was in a porous state and was a smooth powder.

The present disclosure has been described above with reference to embodiments and examples, but the present disclosure is not limited to the above embodiments and examples. Various modifications that can be understood by a person skilled in the art can be made to the configuration and details of the present disclosure within the scope of the present disclosure.

This application claims priority based on Japanese Patent Application No. 2023-138085, filed on August 28, 2023, the disclosure of which is incorporated herein in its entirety.

<Additional Notes>
Some or all of the above-described embodiments and examples may be described as follows, but are not limited to the following supplementary notes.
<Water-soluble bactiol>
(Appendix 1)
A composition comprising bactiol, a solvent, and a nonionic surfactant and/or anionic surfactant.
(Appendix 2)
2. The composition of claim 1, wherein the solvent is an ester oil, a hydrocarbon oil, and/or an ether oil.
(Appendix 3)
3. The composition of claim 1 or 2, wherein the solvent is an ester oil.
(Appendix 4)
4. The composition of any one of claims 1 to 3, wherein the solvent is caprylic/capric triglyceride.
(Appendix 5)
The composition according to any one of claims 1 to 4, wherein the nonionic surfactant is an ethylene oxide condensation type, a polyhydric alcohol ester type, and/or a polyhydric alcohol condensation type.
(Appendix 6)
6. The composition according to any one of claims 1 to 5, wherein the nonionic surfactant is an ethylene oxide condensation type.
(Appendix 7)
The composition according to any one of claims 1 to 6, wherein the nonionic surfactant is a polyoxyethylene polyoxypropylene alkyl ether.
(Appendix 8)
The composition of claim 7, wherein the polyoxyethylene polyoxypropylene alkyl ethers are polyoxyethylene polyoxypropylene decyl tetradecyl ether, polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene monobutyl ether, polyoxyethylene polyoxypropylene, hydrogenated lanolin, and/or polyoxyethylene polyoxypropylene glycerin ether.
(Appendix 9)
The composition according to any one of claims 1 to 8, wherein the anionic surfactant is a carboxylic acid-based, higher alcohol-based, sulfonic acid-based, peptide-based, olefin-based, amino acid-based, taurine-based, and/or lactic acid-based surfactant.
(Appendix 10)
The composition according to any one of claims 1 to 9, wherein the content of the bactiol is 0.001 to 5% by weight, based on the total weight of the composition.
(Appendix 11)
11. The composition according to any one of claims 1 to 10, wherein the content of the solvent is greater than 0% by mass to 5% by mass, based on the total mass of the composition.
(Appendix 12)
12. The composition according to any one of claims 1 to 11, wherein the content of the anionic surfactant and/or the nonionic surfactant is 2 to 20% by mass, based on the total mass of the composition.
(Appendix 13)
13. The composition of any one of claims 1 to 12, further comprising a block copolymer.
(Appendix 14)
The composition of any one of claims 1 to 13, wherein the block copolymer is a polyamino acid-polyethylene glycol block copolymer, a polylactic acid-polyethylene glycol block copolymer, a polylactic acid-polyglycolic acid block copolymer, a polysarcosine-polyethylene glycol block copolymer, and/or a polyoxazoline-polysiloxane block copolymer.
(Appendix 15)
15. The composition of any one of claims 1 to 14, wherein the block copolymer is oligopeptide-56 amide PEG-75 methyl ether.
(Appendix 16)
16. The composition according to any one of claims 13 to 15, wherein the content of the block copolymer is 0.02 to 2% by mass, based on the total mass of the composition.
(Appendix 17)
17. The composition of any one of claims 1 to 16, further comprising a dispersion medium.
(Appendix 18)
18. The composition according to claim 17, wherein the content of the dispersion medium is greater than 0% by mass to 5% by mass, based on the total mass of the composition.
(Appendix 19)
19. The composition of any one of claims 1 to 18, having a transmittance at 600 nm of 50% or more.
(Appendix 20)
20. The composition of any one of claims 1 to 19, which is an oil-in-water emulsion composition.
(Appendix 21)
21. The composition of claim 20, wherein the emulsion is a nanoemulsion and/or a microemulsion.
(Appendix 22)
22. The composition of claim 20 or 21, wherein the oil droplets in the composition have an average particle size of 100 nm or less.
(Appendix 23)
23. A composition for application to the skin comprising a composition according to any one of claims 1 to 22.
<Stable bactiol>
(Appendix 24)
Contains bactiol and carotenoids
A composition, wherein the mass ratio (B:C) of the bactiol (B) to the carotenoid (C) is 1:10 to 2:1.
(Appendix 25)
25. The composition of claim 24, wherein the carotenoid is a retinoid.
(Appendix 26)
26. The composition of claim 25, wherein the retinoid is retinol palmitate.
(Appendix 27)
Contains particles,
27. The composition of any one of claims 24 to 26, wherein the particles comprise the bactiol and the carotenoid.
(Appendix 28)
28. The composition according to any one of claims 24 to 27, further comprising an oil.
(Appendix 29)
29. The composition of claim 28, wherein the oil is a liquid oil, an ester oil, a silicone oil, a hydrocarbon oil, a higher alcohol, and/or a fatty acid.
(Appendix 30)
30. The composition of claim 29, wherein the oil is squalane.
(Appendix 31)
31. The composition according to claim 30, wherein the content of the oil is 55 to 99 mass% based on the total mass of the composition.
(Appendix 32)
32. The composition of any one of claims 24 to 31, further comprising a gelling agent.
(Appendix 33)
33. The composition according to claim 32, wherein the content of the gelling agent is 0.5 to 50% by mass, based on the total mass of the composition.
(Appendix 34)
35. The composition of any one of claims 24 to 34, which is an oil gel composition.
(Appendix 35)
35. A composition for application to the skin comprising the composition of any of claims 24 to 34.
<Permeating bactiol>
(Appendix 36)
Contains liposomes,
The liposome comprises bactiol, complex lipids, and sterols.
(Appendix 37)
37. The composition of claim 36, wherein the complex lipid is a phospholipid, a glycolipid, a lipoprotein, and/or a sulfolipid.
(Appendix 38)
38. The composition of claim 36 or 37, wherein the complex lipid is a phospholipid.
(Appendix 39)
39. The composition of any one of claims 36 to 38, wherein the complex lipid is phosphatidylcholine.
(Appendix 40)
40. The composition of any one of claims 36 to 39, wherein the sterol is cholesterol.
(Appendix 41)
41. The composition of any one of claims 36 to 40, wherein the bactiol content is greater than 0% by weight to 40% by weight, based on the total weight of the liposome.
(Appendix 42)
42. The composition according to any one of claims 36 to 41, wherein the content of the complex lipid is 25 to 75% by mass based on the total mass of the liposome.
(Appendix 43)
43. The composition according to any one of claims 36 to 42, wherein the content of the sterols is 2 to 20% by mass, based on the total mass of the liposome.
(Appendix 44)
44. The composition of any one of claims 36 to 43, wherein the liposome is a pH-responsive liposome.
(Appendix 45)
45. The composition of any one of claims 36 to 44, wherein the liposomes have an average particle size of 50 to 1100 nm.
(Appendix 46)
46. The composition of any one of claims 36 to 45, wherein the liposome further comprises an anionic substance.
(Appendix 47)
47. The composition of claim 46, wherein the anionic material is a fatty acid.
(Appendix 48)
48. The composition of claim 46 or 47, wherein the anionic substance is palmitic acid and/or stearic acid.
(Appendix 49)
49. The composition according to any one of claims 46 to 48, wherein the content of the anionic substance is 2.5 to 15% by mass, based on the total mass of the liposome.
(Appendix 50)
50. The composition of any one of claims 36 to 49, wherein the liposome further comprises a zwitterionic surfactant.
(Appendix 51)
The composition of claim 50, wherein the zwitterionic surfactant is at least one selected from the group consisting of N-alkyl-N,N-dimethylamino acid betaines including lauryl dimethylaminoacetate betaine (lauryl betaine); fatty acid amidoalkyl-N,N-dimethylamino acid betaines including cocamidopropyl betaine and lauramidopropyl betaine; imidazoline-type betaines including sodium cocoamphoacetate and sodium lauroamphoacetate; alkyl sulfobetaines including alkyl dimethyl taurine; sulfate-type betaines including alkyl dimethyl aminoethanol sulfate; and phosphate-type betaines including alkyl dimethyl aminoethanol phosphate.
(Appendix 52)
52. The composition according to claim 50 or 51, wherein the content of the zwitterionic surfactant is 5 to 20% by mass, based on the total mass of the liposome.
(Appendix 53)
53. A composition for application to the skin comprising a composition according to any one of claims 36 to 52.
<Microcapsule-type bactiol>
(Appendix 54)
Contains bactiol and silica
A composition, wherein the bactiol is supported on the silica.
(Appendix 55)
55. The composition of claim 54, wherein the bactiol content is 0.01 to 30% by weight, based on the total weight of the composition.
(Appendix 56)
56. The composition according to claim 54 or 55, wherein the content of the silica is 60 to 95% by mass, based on the total mass of the composition.
(Appendix 57)
57. The composition of any one of claims 54 to 56, wherein the silica comprises porous silica.
(Appendix 58)
58. The composition of any one of claims 54 to 57, wherein the bactiol is supported at least inside the porous silica.
(Appendix 59)
59. The composition of any of claims 54 to 58, having an average particle size of 0.01 to 500 μm.
(Appendix 60)
60. The composition of any one of claims 54 to 59, further comprising a higher alcohol.
(Appendix 61)
61. The composition of claim 60, wherein the higher alcohol is behenyl alcohol.
(Appendix 62)
62. The composition according to claim 60 or 61, wherein the content of the higher alcohol is greater than 0% by mass to 30% by mass, based on the total mass of the composition.
(Appendix 63)
63. A composition for application to the skin comprising the composition of any of claims 54 to 62.

As described above, the present disclosure can provide a composition in which the dispersibility of bactiol in water-soluble solvents is improved, a composition in which the thermal stability of carotenoids is improved, a composition in which the permeability of bactiol through the stratum corneum is improved, and/or a powder containing bactiol. For this reason, the present invention can be said to be extremely useful, for example, in the fields of cosmetics, topical skin preparations, etc.

Claims (63)

A composition comprising bactiol, a solvent, and a nonionic surfactant and/or anionic surfactant. The composition of claim 1, wherein the solvent is an ester oil, a hydrocarbon oil, and/or an ether oil. The composition according to claim 1 or 2, wherein the solvent is an ester oil. The composition of any one of claims 1 to 3, wherein the solvent is caprylic/capric triglyceride. The composition according to any one of claims 1 to 4, wherein the nonionic surfactant is an ethylene oxide condensation type, a polyhydric alcohol ester type, and/or a polyhydric alcohol condensation type. The composition according to any one of claims 1 to 5, wherein the nonionic surfactant is an ethylene oxide condensation type. The composition according to any one of claims 1 to 6, wherein the nonionic surfactant is a polyoxyethylene polyoxypropylene alkyl ether. The composition of claim 7, wherein the polyoxyethylene polyoxypropylene alkyl ethers are polyoxyethylene polyoxypropylene decyl tetradecyl ether, polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene monobutyl ether, polyoxyethylene polyoxypropylene, hydrogenated lanolin, and/or polyoxyethylene polyoxypropylene glycerin ether. The composition according to any one of claims 1 to 8, wherein the anionic surfactant is a carboxylic acid-based, higher alcohol-based, sulfonic acid-based, peptide-based, olefin-based, amino acid-based, taurine-based, and/or lactic acid-based surfactant. The composition according to any one of claims 1 to 9, wherein the content of the bactiol is 0.001 to 5% by mass, based on the total mass of the composition. The composition according to any one of claims 1 to 10, wherein the content of the solvent is greater than 0% by mass and greater than 5% by mass, based on the total mass of the composition. The composition according to any one of claims 1 to 11, wherein the content of the anionic surfactant and/or the nonionic surfactant is 2 to 20 mass % based on the total mass of the composition. The composition according to any one of claims 1 to 12, further comprising a block copolymer. The composition according to any one of claims 1 to 13, wherein the block copolymer is a polyamino acid-polyethylene glycol block copolymer, a polylactic acid-polyethylene glycol block copolymer, a polylactic acid-polyglycolic acid block copolymer, a polysarcosine-polyethylene glycol block copolymer, and/or a polyoxazoline-polysiloxane block copolymer. The composition according to any one of claims 1 to 14, wherein the block copolymer is oligopeptide-56 amide PEG-75 methyl ether. The composition according to any one of claims 13 to 15, wherein the content of the block copolymer is 0.02 to 2 mass% based on the total mass of the composition. The composition according to any one of claims 1 to 16, further comprising a dispersion medium. The composition according to claim 17, wherein the content of the dispersion medium is greater than 0% by mass and greater than 5% by mass, based on the total mass of the composition. A composition according to any one of claims 1 to 18, having a transmittance of 50% or more at 600 nm. The composition according to any one of claims 1 to 19, which is an oil-in-water emulsion composition. The composition of claim 20, wherein the emulsion is a nanoemulsion and/or a microemulsion. The composition according to claim 20 or 21, wherein the oil droplets in the composition have an average particle size of 100 nm or less. A composition for application to the skin comprising a composition according to any one of claims 1 to 22. Contains bactiol and carotenoids
A composition, wherein the mass ratio (B:C) of the bactiol (B) to the carotenoid (C) is 1:10 to 2:1. The composition of claim 24, wherein the carotenoid is a retinoid. The composition of claim 25, wherein the retinoid is retinol palmitate. Contains particles,
27. The composition of any one of claims 24 to 26, wherein the particles comprise the bactiol and the carotenoid. The composition according to any one of claims 24 to 27, further comprising an oil. The composition according to claim 28, wherein the oil is a liquid oil, an ester oil, a silicone oil, a hydrocarbon oil, a higher alcohol, and/or a fatty acid. The composition according to claim 29, wherein the oil is squalane. The composition according to claim 30, wherein the content of the oil is 55 to 99 mass % based on the total mass of the composition. The composition according to any one of claims 24 to 31, further comprising a gelling agent. The composition according to claim 32, wherein the content of the gelling agent is 0.5 to 50% by mass, based on the total mass of the composition. The composition according to any one of claims 24 to 34, which is an oil gel composition. A composition for application to the skin comprising a composition according to any one of claims 24 to 34. Contains liposomes,
The liposome comprises bactiol, complex lipids, and sterols. The composition of claim 36, wherein the complex lipid is a phospholipid, a glycolipid, a lipoprotein, and/or a sulfolipid. The composition according to claim 36 or 37, wherein the complex lipid is a phospholipid. The composition according to any one of claims 36 to 38, wherein the complex lipid is a phosphatidylcholine. The composition according to any one of claims 36 to 39, wherein the sterol is cholesterol. The composition according to any one of claims 36 to 40, wherein the content of the bactiol is greater than 0% by mass to 40% by mass, based on the total mass of the liposome. The composition according to any one of claims 36 to 41, wherein the content of the complex lipid is 25 to 75 mass% based on the total mass of the liposome. The composition according to any one of claims 36 to 42, wherein the content of the sterols is 2 to 20% by mass based on the total mass of the liposome. The composition of any one of claims 36 to 43, wherein the liposome is a pH-responsive liposome. The composition according to any one of claims 36 to 44, wherein the liposomes have an average particle size of 50 to 1100 nm. The composition according to any one of claims 36 to 45, wherein the liposome further comprises an anionic substance. The composition of claim 46, wherein the anionic substance is a fatty acid. The composition of claim 46 or 47, wherein the anionic substance is palmitic acid and/or stearic acid. The composition according to any one of claims 46 to 48, wherein the content of the anionic substance is 2.5 to 15% by mass based on the total mass of the liposome. The composition of any one of claims 36 to 49, wherein the liposome further comprises a zwitterionic surfactant. The composition according to claim 50, wherein the zwitterionic surfactant is at least one selected from the group consisting of N-alkyl-N,N-dimethylamino acid betaines including lauryl dimethylaminoacetate betaine (lauryl betaine); fatty acid amidoalkyl-N,N-dimethylamino acid betaines including cocamidopropyl betaine and lauramidopropyl betaine; imidazoline-type betaines including sodium cocoamphoacetate and sodium lauroamphoacetate; alkyl sulfobetaines including alkyl dimethyl taurine; sulfate-type betaines including alkyl dimethyl aminoethanol sulfate; and phosphate-type betaines including alkyl dimethyl aminoethanol phosphate. The composition according to claim 50 or 51, wherein the content of the zwitterionic surfactant is 5 to 20% by mass based on the total mass of the liposome. A composition for application to the skin comprising a composition according to any one of claims 36 to 52. Contains bactiol and silica
A composition, wherein the bactiol is supported on the silica. The composition according to claim 54, wherein the content of the bactiol is 0.01 to 30% by mass, based on the total mass of the composition. The composition according to claim 54 or 55, wherein the content of the silica is 60 to 95 mass % based on the total mass of the composition. The composition of any one of claims 54 to 56, wherein the silica comprises porous silica. The composition according to any one of claims 54 to 57, wherein the bactiol is supported at least inside the porous silica. The composition according to any one of claims 54 to 58, having an average particle size of 0.01 to 500 μm. The composition according to any one of claims 54 to 59, further comprising a higher alcohol. The composition of claim 60, wherein the higher alcohol is behenyl alcohol. The composition according to claim 60 or 61, wherein the content of the higher alcohol is greater than 0% by mass to 30% by mass, based on the total mass of the composition. 63. A composition for application to the skin comprising a composition according to any one of claims 54 to 62.