Aqueous composition and method for producing the same

Abstract

To provide means that enables the stable incorporation of cholesterol into an aqueous medium.SOLUTION: One aspect of the present invention is a method for producing an aqueous composition containing cholesterol, comprising the steps: (I) preparing a solution containing (a) cholesterol, (b) a surfactant with a sterol skeleton, (c1) water, and (d) a polyol; and (II) subjecting the solution to high-pressure emulsification, to produce a concentrate with cholesterol dispersed therein. The mass ratio of (b) the surfactant with a sterol skeleton to (a) cholesterol, [(b) / (a)], is 3 or more. The polyol (d) comprises: (d1) a first polyol which is a diol with 5 to 10 carbon atoms; and (d2) a second polyol, which is at least one selected from diols with 4 or fewer carbon atoms and glycerol. The mass ratio of (d1) the first polyol to (a) cholesterol, [(d1) / (a)], is 3-10, and the mass ratio of (d2) the second polyol to (a) cholesterol, [(d2) / (a)], is 3-10.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an aqueous composition containing cholesterol and a method for producing the same. [Background technology]

[0002] Cholesterol is one of the components that form the lamellar structure in the stratum corneum of the epidermis, and plays an important role in maintaining the barrier function. It is believed that if the ability to synthesize cholesterol in the epidermis decreases, the barrier function decreases and the skin's ability to recover from rough skin decreases. For this reason, cholesterol is commonly used in cosmetics, quasi-drugs, pharmaceuticals, etc., in the hope of maintaining the barrier function and improving rough skin. However, cholesterol is an oil-soluble substance that is solid at room temperature and has low solubility in cosmetic base materials (especially aqueous cosmetic base materials), so there was a problem that only small amounts could be blended.

[0003] Solubilization is known as a method for stably dispersing oily components in aqueous media. Solubilization refers to the incorporation of poorly soluble or insoluble substances in water, such as oily components, into an aqueous solvent using a solubilizer such as a surfactant to make the substance thermodynamically stable and transparent or translucent. Various attempts have been made to solubilize oily materials, but it is generally difficult to solubilize oily materials with high crystallinity, such as cholesterol, and various investigations have been made into the blending of alcohols, fatty acid esters, and the like. For example, Patent Document 1 discloses a solubilized composition characterized by blending a nonionic surfactant with an HLB of 11 to 16, diglyceryl monoisostearate and / or diglyceryl monooleate, an anionic surfactant, cholesterol and / or phytosterol, and ethanol. Another method for stably dispersing oily components in an aqueous medium is the emulsification method, but emulsion compositions containing cholesterol are usually cloudy, and it is difficult to make them transparent, and there is also a problem with the feel when used. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent Publication No. 2013-227293 Summary of the Invention [Problem to be solved by the invention]

[0005] To provide a means for stably incorporating cholesterol into an aqueous medium. [Means for solving the problem]

[0006] The present invention includes the following embodiments. [1] A method for producing an aqueous composition containing cholesterol, comprising the steps of: A step (I) of preparing a solution containing (a) cholesterol, (b) a surfactant having a sterol skeleton, (c1) water, and (d) a polyol; A step (II) of subjecting the solution to a high-pressure emulsification treatment to obtain a concentrated solution in which cholesterol is dispersed; Including, the mass ratio of the (b) surfactant having a sterol skeleton to the (a) cholesterol [(b) / (a)] is 3 or more; The (d) polyol includes (d1) a first polyol which is a diol having 5 to 10 carbon atoms, and (d2) a second polyol which is at least one of a diol having 4 or less carbon atoms and glycerol, a mass ratio of the (d1) first polyol to the (a) cholesterol [(d1) / (a)] is 3 to 10; The method, wherein the mass ratio of the (d2) second polyol to the (a) cholesterol [(d2) / (a)] is 3 to 10. [2] The method according to [1], wherein the mass ratio of the (c1) water to the (a) cholesterol [(c1) / (a)] is 2 to 11. [3] The method according to [1] or [2], wherein the treatment pressure in the high-pressure emulsification treatment is 100 to 200 MPa. [4] The method according to any one of [1] to [3], wherein in the step (II), a high-pressure emulsifier selected from a Microfluidizer, a Nanomizer, and a Starburst is used for the high-pressure emulsification treatment. [5] In the step (II), a microfluidizer is used for the high-pressure emulsification treatment; the mass ratio of the (c1) water to the (a) cholesterol [(c1) / (a)] is 3 to 11; or In the step (II), a Nanomizer is used for the high-pressure emulsification treatment, The method according to [4], wherein a mass ratio of the (c1) water to the (a) cholesterol [(c1) / (a)] is 5 to 11. [6] The method according to any one of [1] to [5], further comprising a step (III) of mixing the concentrate obtained in the step (II) with (c2) water to obtain a diluted solution. [7] (b) The method according to any one of [1] to [6], wherein the surfactant having a sterol skeleton includes at least one of polyoxyethylene cholesteryl ether and polyoxyethylene phytosteryl ether. [8] The method according to any one of [1] to [7], wherein the (d) polyol comprises a first polyol which is pentanediol and a second polyol selected from butylene glycol and propanediol. [9] An aqueous composition containing cholesterol, comprising: (a) cholesterol, (b) a surfactant having a sterol skeleton, (c) water, and (d) a polyol; the mass ratio of the (b) surfactant having a sterol skeleton to the (a) cholesterol [(b) / (a)] is 3 or more; The (d) polyol includes (d1) a first polyol which is a diol having 5 or more carbon atoms, and (d2) a second polyol which is at least one of a diol having 4 or less carbon atoms and glycerol, a mass ratio of the (d1) first polyol to the (a) cholesterol [(d1) / (a)] is 3 to 10; A composition, wherein the mass ratio of the (d2) second polyol to the (a) cholesterol [(d2) / (a)] is 3 to 10.

[10] The composition is in the form of an O / W emulsion, The composition according to [9], wherein the median diameter of the oil phase is 50 to 210 nm.

[11] The composition described in [9] or

[10] , having a light transmittance of 80% or more at a wavelength of 700 nm.

[12] The composition according to any one of [9] to

[11] , wherein the content of the (a) cholesterol is 0.1 to 3 mass% based on the total amount of the composition.

[13] The composition according to any one of [9] to

[12] , which is a cosmetic or a topical skin preparation.

[14] The composition described in any of [9] to

[13] , wherein the dosage form is a mist, spray or lotion. Effect of the Invention

[0007] The present invention has one or more of the following advantages. (1) According to the present invention, there is provided an aqueous composition (concentrate and diluent) containing cholesterol stably and a method for producing the same. The aqueous composition can be suitably used as a cosmetic, quasi-drug, pharmaceutical, etc. (e.g., a cosmetic or topical skin preparation). (2) In some embodiments, the aqueous composition has at least one of high transparency and excellent stability (preferably high transparency and excellent stability). In particular, the aqueous composition can stably incorporate cholesterol with a small amount of surfactant. In a preferred embodiment, the aqueous composition can suppress or reduce cholesterol precipitation, and can be suitably used in the form of a mist, spray, lotion, or the like. (3) In some embodiments, the aqueous composition is excellent in long-term stability, suppressing cholesterol precipitation over time. In a preferred embodiment, a concentrated solution is obtained in which precipitation of cholesterol is suppressed even 28 days after preparation. In a preferred embodiment, a diluted solution is obtained in which precipitation of cholesterol is suppressed even 6 months after preparation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Hereinafter, the embodiments of the present invention will be described in detail. Note that the present invention is not limited to the following embodiments, and can be modified and carried out as desired without departing from the gist of the present invention. The upper and lower limit values ​​of the numerical ranges described in this specification can be arbitrarily combined. For example, when "X to Y" and "Z to W" are described, the ranges of "X to W" and "Z to Y" are also included in the scope of the present invention as numerical ranges. In addition, the numerical range "lower limit value to upper limit value" described in this specification means not less than the lower limit value and not more than the upper limit value, unless otherwise specified.

[0009] In this specification, "transparent" means that the transmittance of light at a wavelength of 700 nm is 40% or more (more preferably 60% or more, even more preferably 80% or more, and particularly preferably 90% or more). In this specification, the transmittance of light at a wavelength of 700 nm can be measured by an ultraviolet-visible spectrophotometer. "Transparent" compositions include not only completely transparent compositions, but also "semi-transparent" compositions whose transmittance is within the above range. As used herein, an "aqueous" composition refers to one in which the external phase of the composition is an aqueous component. As used herein, "stability" refers to the reduction of cholesterol precipitation or cloudiness. In some embodiments, "stability" refers to the absence of visible cholesterol precipitation after standing at room temperature (e.g., 20 to 30°C, particularly 25°C). As used herein, "long-term stability" refers to no visible precipitation of cholesterol over time after storage at room temperature (e.g., 20 to 30°C, particularly 25°C) for a certain period of time (e.g., 7 days, 14 days, 21 days, 28 days, 30 days, 60 days, or 90 days). In this specification, the term "oil-based component" refers to a component that is generally used as an oil-based component in the field of cosmetics. For example, it refers to a component that has a solubility in water of less than 0.1% by mass (less than 1 g / L) at 25°C. Note that the oil-based component does not include surfactants.

[0010] (aqueous composition) One embodiment of the present invention relates to an aqueous composition containing cholesterol (hereinafter, also simply referred to as "aqueous composition"). The aqueous composition of this embodiment includes (a) cholesterol, (b) a surfactant having a sterol skeleton, (c) water, and (d) a polyol, in which the mass ratio [(b) / (a)] of the surfactant having the sterol skeleton (b) to the cholesterol (a) is 3 or more, and the polyol (d) includes (d1) a first polyol which is a diol having 5 or more carbon atoms, and (d2) a second polyol which is at least one of a diol having 4 or less carbon atoms or glycerol, in which the mass ratio [(d1) / (a)] of the first polyol (d1) to the cholesterol (a) is 3 to 10, and the mass ratio [(d2) / (a)] of the second polyol (d2) to the cholesterol (a) is 3 to 10. By blending (a) cholesterol with (b) a surfactant having a sterol skeleton, (d1) a first polyol, and (d2) a second polyol in a specific ratio (the (b) / (a) ratio, the (d1) / (a) ratio, or the (d2) / (a) ratio), it is possible to stably disperse cholesterol in an aqueous medium containing water, and to obtain an aqueous composition with excellent transparency. Each of the components in the aqueous composition of the present invention will be described below.

[0011] (Components) (a) Cholesterol Cholesterol is an active ingredient of the aqueous composition, and may have skin care effects such as enhancing the barrier function of the skin, suppressing water evaporation from the inside of the skin, and enhancing moisturizing power.

[0012] The content of cholesterol in the aqueous composition is not limited as long as cholesterol can be stably dispersed in the aqueous phase, and is appropriately set depending on the application and dosage form.

[0013] In some embodiments, the cholesterol content of the aqueous composition is 0.1 to 3% by mass based on the total amount (total mass) of the aqueous composition. If the cholesterol content is 0.1 to 3% by mass of the aqueous composition, it can have skin care effects such as enhancing the barrier function of the skin, suppressing water evaporation from the inside of the skin, and enhancing moisturizing power, and can be suitably used, for example, as a cosmetic or skin external preparation. In general, cholesterol precipitation and clouding tend to occur more easily with an increase in cholesterol concentration. From the viewpoint of transparency and stability (reduction and suppression of cholesterol precipitation and clouding), it is more preferably 0.1 to 2% by mass, even more preferably 0.1 to 1.5% by mass, and particularly preferably 0.1 to 1.0% by mass. In some embodiments, the cholesterol content is 1 to 3 mass % (preferably 1 to 2 mass %, and more preferably 1 to 1.5 mass %) relative to the total amount (total mass) of the composition. An aqueous composition of such a concentration can be produced by diluting an aqueous cholesterol concentrate in the production method described below, and therefore is sometimes referred to as a "diluted solution" in this specification.

[0014] In some embodiments, the aqueous composition may contain 3% by mass or more of cholesterol. Such a high-concentration cholesterol-containing composition can also be used to prepare the above-mentioned diluted solution by dilution. From this perspective, in this specification, an aqueous composition containing high-concentration cholesterol (e.g., 3% by mass or more) is sometimes referred to as a "concentrate". The cholesterol content in the concentrate is, for example, 3 to 10% by mass (more preferably 3 to 7% by mass, and even more preferably 3 to 5% by mass) based on the total amount (total mass) of the concentrate.

[0015] (b) Surfactants with a sterol skeleton The aqueous composition contains a surfactant having a sterol skeleton. By containing a surfactant having a sterol skeleton together with cholesterol, cholesterol can be stably dispersed in water, and thus a composition having excellent transparency and in which precipitation or clouding of cholesterol is reduced or inhibited can be obtained.

[0016] The surfactant having a sterol skeleton in the present invention is a surfactant having a sterol skeleton in a lipophilic group (hydrophobic part). The sterol skeleton is an alcohol having a hydroxyl group bonded to the 3-position of a cyclopentanohydrophenanthrene ring shown in the following formula, and the surfactant having a sterol skeleton is a compound having a hydrophilic group bonded to this sterol skeleton. In addition, the symbols A to D in the following formula represent each ring constituting the cyclopentanohydrophenanthrene ring, and the numbers represent the position numbers of the carbons constituting the cyclopentanohydrophenanthrene ring. The sterol skeleton of the lipophilic group may have a double bond in the cyclopentanohydrophenanthrene ring.

[0017] [ka]

[0018] Among them, sterols having a double bond in the B ring or stanols composed of a saturated ring are preferred.Specific examples include phytosterols such as β-sitosterol, campesterol, stigmasterol, brassicasterol, and the like, or stanols thereof, cholesterol, cholestanol, lanosterol, ergosterol, and the like, and are preferably phytosterols, phytostanols, cholesterol, or cholestanol, and more preferably phytosterol or cholesterol.

[0019] The hydrophilic group is not particularly limited, and examples thereof include nonionic hydrophilic groups such as polyoxyalkylene chains (e.g., polyoxyethylene (POE) chains, polyoxypropylene (POP) chains, etc.), polyglycerin, polyglucosides, sorbitan, and sucrose; anionic hydrophilic groups such as carboxylates, sulfonates, sulfates, and phosphates; and cationic hydrophilic groups such as aliphatic amine salts and quaternary ammonium salts. The alkylene in the polyoxyalkylene chain preferably has 1 to 4 carbon atoms, more preferably has 1 or 2 carbon atoms, and particularly preferably is ethylene. Among these, the hydrophilic group is preferably a nonionic hydrophilic group, more preferably a polyoxyalkylene chain, and even more preferably a polyoxyethylene (POE) chain. The number of moles of polyoxyalkylene chains (preferably polyoxyethylene (POE) chains) added is not particularly limited, but is preferably 12 or more, more preferably 15 or more, and even more preferably 18 or more. The number of moles of polyoxyalkylene chains (preferably polyoxyethylene (POE) chains) added is preferably 25 or less, more preferably 24 or less, and even more preferably 22 or less. In some embodiments, the number of moles of polyoxyalkylene chains (preferably polyoxyethylene (POE)) added is preferably 12 to 25, more preferably 15 to 24, and even more preferably 18 to 22.

[0020] The surfactant having a sterol skeleton is, for example, a surfactant in which a polyoxyalkylene is ether-bonded to the sterol skeleton. More specifically, the surfactant may be, but is not limited to, polyoxyalkylene cholesteryl ether (e.g., POE cholesteryl ether, POP cholesteryl ether), polyoxyalkylene phytosteryl ether (e.g., POE phytosteryl ether, POP phytosteryl ether), polyoxyalkylene cholestanol (e.g., POE cholestanol, POP cholestanol), polyoxyalkylene phytostanol (e.g., POE phytostanol, POP phytostanol), etc. Among them, the surfactant having a sterol skeleton is preferably at least one of polyoxyethylene cholesteryl ether and polyoxyethylene phytosteryl ether in terms of transparency and stability. Furthermore, POE (12-25, more preferably 15-24, even more preferably 18-22) cholesterol and POE (12-25, more preferably 15-24, even more preferably 18-22) phytosteryl ether are preferred.

[0021] The HLB (Hydrophilic-Lipophilic Balance) of the surfactant having a sterol skeleton is not particularly limited, but is preferably 11 or more, more preferably 12 or more, from the viewpoint of improving transparency. The HLB of the surfactant having a sterol skeleton is not particularly limited, but is preferably 16 or less, more preferably 15 or less. The HLB of the surfactant having a sterol skeleton is preferably in the range of 11 to 16, more preferably 12 to 15. In this specification, unless otherwise specified, the HLB value is experimentally determined by comparing the emulsifying power with that of a standard sample.

[0022] The surfactant having a sterol skeleton may be any surfactant having the above-mentioned characteristics, and may be a commercially available product. Examples of commercially available products include, but are not limited to, EMALEX CS series (EMALEX CS-15, EMALEX CS-20, EMALEX CS-24, etc.) manufactured by Nippon Emulsion Co., Ltd. and NIKKOL BPS series (NIKKOL BPS-20, etc.) manufactured by Nikko Chemicals Co., Ltd.

[0023] These surfactants having a sterol skeleton can be used alone or in combination of two or more.

[0024] The content of the (b) surfactant having a sterol skeleton in the aqueous composition is not particularly limited. In some embodiments, when the aqueous composition is a diluted solution, the content of the (b) surfactant having a sterol skeleton in the aqueous composition is preferably 0.5 to 10 mass % based on the total amount of the composition in terms of the feel when used. In some embodiments, when the aqueous composition is a concentrated liquid, the content of the (b) surfactant having a sterol skeleton in the aqueous composition is preferably 9 to 20 mass % based on the total amount of the composition.

[0025] (c) water The water is not particularly limited as long as it is generally used in cosmetics. For example, tap water, ion-exchanged water, distilled water, purified water, etc. can be used.

[0026] The water content is not particularly limited. In some embodiments, the main component of the aqueous composition is water. In some embodiments, when the aqueous composition is a dilution, the content of (c) water is preferably 60% by mass or more, more preferably 70% by mass or more, and even more preferably 80% by mass or more, based on the total amount of the composition, from the viewpoint of transparency. The upper limit is not particularly limited, and is, for example, 99.5% by mass or less, or 97% by mass or less, or 95% by mass or less. In some embodiments, the content of water in the aqueous composition is preferably 60 to 99.5% by mass, more preferably 70 to 97% by mass, and even more preferably 75 to 95% by mass, based on the total amount of the composition.

[0027] In some embodiments, when the aqueous composition is a concentrate, the content of (c1) water is preferably 12% by mass or more, more preferably 15% by mass or more, and even more preferably 20% by mass or more, based on the total amount of the composition, from the viewpoint of stability. The upper limit is not particularly limited, and is, for example, 80% by mass or less, or 70% by mass or less, or 60% by mass or less. In some embodiments, the content of water in the aqueous composition is preferably 12 to 80% by mass or more, more preferably 15 to 70% by mass, and even more preferably 20 to 60% by mass, based on the total amount of the composition.

[0028] (d) Polyol Polyols are amphiphilic, and by incorporating polyols, the dispersibility of cholesterol in water can be improved, which can improve the transparency of the aqueous composition.

[0029] The aqueous composition contains, as the polyol (d), (d1) a first polyol which is a diol having 5 to 10 carbon atoms, and (d2) a second polyol which is at least one of a diol having 4 or less carbon atoms or glycerol. By blending the first polyol and the second polyol together with cholesterol, cholesterol precipitation and cloudiness are suppressed, and an aqueous composition (concentrate / dilute solution) with excellent transparency is obtained. The first polyol and the second polyol within this carbon number range are usually aqueous components, and are components which form an aqueous phase. As used herein, "diol" refers to an aliphatic or alicyclic compound in which two hydroxyl groups are bonded to two different carbons. In addition to compounds having two hydroxyl groups in an aliphatic or alicyclic hydrocarbon chain, "diol" also includes compounds having two hydroxyl groups in a molecular structure in which the aliphatic and / or alicyclic hydrocarbon chains are bonded by an ether bond (-O-).

[0030] (d1) The first polyol, which is a diol having 5 to 10 carbon atoms, is not particularly limited, and examples thereof include pentanediols such as 1,5-pentanediol, 1,4-pentanediol, 1,3-pentanediol, 1,2-pentanediol (pentylene glycol), 2,4-pentanediol, 2,3-pentanediol, and isopentyldiol; 1,2-hexanediol, caprylyl glycol, and dipropylene glycol. Among these, from the viewpoint of safety, diols having 5 to 8 carbon atoms are preferred, diols having 5 to 6 carbon atoms are more preferred, pentanediol and hexanediol are even more preferred, and 1,2-pentanediol is particularly preferred. The first polyol may be used alone or in combination of two or more kinds.

[0031] (d2) The second polyol may be at least one of a diol having 4 or less carbon atoms (for example, propylene glycol, 1,3-propanediol, 1,3-butylene glycol, etc.) and glycerol. Among these, 1,3-propanediol and glycerol are preferred. The second polyol may be used alone or in combination of two or more kinds.

[0032] In some embodiments, the first polyol is pentanediol and the second polyol is selected from butylene glycol and propanediol. In one embodiment, the first polyol is pentanediol (more preferably 1,2-pentanediol) and the second polyol is butylene glycol. In one embodiment, the first polyol is pentanediol (more preferably 1,2-pentanediol) and the second polyol is propanediol.

[0033] The contents of the first polyol (d1) and the second polyol (d2) are not particularly limited, and may be adjusted according to the amount of cholesterol to be blended so as to satisfy the (d1) / (a) ratio and the (d2) / (a) ratio.

[0034] In some embodiments, when the aqueous composition is a diluted solution, from the viewpoints of stability and safety, the content of the first polyol (d1) is preferably 3 to 10 mass %, more preferably 4 to 8 mass %, and even more preferably 4 to 6 mass %, based on the total amount of the composition. In some embodiments, when the aqueous composition is a concentrated liquid, from the viewpoint of stability, the content of the first polyol (d1) is preferably 9 to 30 mass %, more preferably 10 to 25 mass %, and even more preferably 12 to 24 mass %, based on the total amount of the composition.

[0035] In some embodiments, when the aqueous composition is a diluted solution, from the viewpoint of stability, the content of the second polyol (d2) is preferably 3 to 10 mass %, more preferably 4 to 8 mass %, and even more preferably 4 to 6 mass %, based on the total amount of the composition.

[0036] In some embodiments, when the aqueous composition is a concentrated liquid, the content of the second polyol (d2) is preferably 9 to 30 mass %, more preferably 10 to 30 mass %, and even more preferably 12 to 28 mass %, based on the total amount of the composition.

[0037] In some embodiments, when the aqueous composition is a diluted solution, from the viewpoint of stability, the total content of the first polyol (d1) and the second polyol (d2) is preferably 6 to 15 mass%, more preferably 6 to 10 mass%, and even more preferably 6 to 8 mass%, based on the total amount of the composition.

[0038] In some embodiments, when the aqueous composition is a concentrated liquid, from the viewpoint of stability, the total content of the first polyol (d1) and the second polyol (d2) is preferably 28 to 40 mass%, more preferably 30 to 38 mass%, and even more preferably 32 to 36 mass%, based on the total amount of the composition.

[0039] The aqueous composition may contain (d1) another polyol other than the first polyol and the second polyol. Other polyols include, for example, diglycerin, polyglycerin, polyethylene glycol, and polyoxyethylene methyl glucoside. If the amount of other polyol is large, it may have a negative effect on transparency, stability, etc. Therefore, the amount of other polyol is preferably 5% by mass or less of the total mass, more preferably 3% by mass or less, even more preferably 1% by mass or less, and particularly preferably 0.5% by mass or less. In some embodiments, the aqueous composition is substantially free of other polyol. In some embodiments, the aqueous composition is free of other polyol. By using a small amount or no other polyol, transparency and stability can be improved.

[0040] (e) Other ingredients In addition to the above components (a) to (c), the aqueous composition may contain (e1) an oil component other than cholesterol, (e2) other surfactants, and (e3) other aqueous components.

[0041] (e1) Oily components other than cholesterol The aqueous composition may contain an oily component other than cholesterol. If the amount of oily components other than cholesterol is large, it may have a negative effect on transparency, stability, etc. Therefore, cholesterol is preferably 95% by mass or more of the total mass of the oily components, more preferably 98% by mass or more, and even more preferably substantially 100% by mass. In some embodiments, the aqueous composition is substantially free of oily components other than cholesterol (such as non-water-soluble solvents). In some embodiments, the aqueous composition is free of oily components other than cholesterol. By configuring the composition to contain a small amount or no oily components other than cholesterol, transparency and stability can be improved.

[0042] The oily component other than cholesterol is not particularly limited, but examples thereof include higher monoalcohols, hydrocarbons, ester oils, fats and oils, fatty acids, waxes, silicone oils, etc. These may be used alone or in combination of two or more.

[0043] The higher monoalcohol is not particularly limited, but is preferably a straight-chained one, more preferably a straight-chained higher monoalcohol having 12 to 22 carbon atoms (more preferably 14 to 22 carbon atoms, and even more preferably 16 to 22 carbon atoms). Specific examples include cetyl alcohol, stearyl alcohol, cetostearyl alcohol, behenyl alcohol, and the like. The hydrocarbon is not particularly limited, and examples thereof include liquid paraffin, squalane, α-olefin oligomer, petrolatum, and microcrystalline wax. The ester oil is not particularly limited, and examples thereof include cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, 2-hexyldecyl 2-ethylhexanoate, 2-octyldodecyl myristate, 2-hexyldecyl myristate, isononyl isononanoate, 2-ethylhexyl isononanoate, isodecyl pivalate, isostearyl pivalate, 2-hexyldecyl stearate, isostearyl isostearate, isopropyl isostearate, pentaerythritol tetraisostearate, glyceryl tri-2-ethylhexanoate, caprylic / capric triglyceride, myristyl myristate, and cetyl palmitate. The oils and fats are not particularly limited, and examples thereof include olive oil, shea butter, grape seed oil, and the like. The wax is not particularly limited, and examples thereof include jojoba oil, beeswax, candelilla wax, and the like. The fatty acid is not particularly limited, and examples thereof include myristic acid, palmitic acid, and stearic acid.

[0044] In some embodiments, the aqueous composition is free of higher monoalcohols. In some embodiments, the aqueous composition is free of hydrocarbons. In some embodiments, the aqueous composition is free of ester oils. In some embodiments, the aqueous composition is free of fats and oils. In some embodiments, the aqueous composition is free of fatty acids. In some embodiments, the aqueous composition is free of waxes. In some embodiments, the aqueous composition is free of silicone oils.

[0045] (e2) Other surfactants The aqueous composition may contain (b) a surfactant other than the surfactant having a sterol skeleton (another surfactant) as necessary. Other surfactants are not particularly limited, but may be, for example, alkyl ether surfactants such as polyoxyethylene alkyl ether and polyoxyethylene polyoxypropylene alkyl ether; polyoxyethylene fatty acid ester; sorbitan fatty acid esters such as polyoxyethylene sorbitan fatty acid ester and monopalmitic acid sorbitan; polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil isostearate, polyoxyethylene sorbitol tetra fatty acid ester, polyoxyethylene phytosterol, glycerin fatty acid esters such as lipophilic monostearate glyceryl and monostearate tetraglyceryl, glycerin fatty acid esters such as polyglycerin fatty acid ester, sucrose fatty acid ester, polyethylene glycol distearate, etc., may be used alone or in combination of two or more. Among these, it is preferable to use at least one of monopalmitic acid sorbitan, lipophilic monostearate glyceryl, and monostearate tetraglyceryl.

[0046] The content of the other surfactant is not particularly limited, but from the viewpoints of transparency and stability, it is preferably 0 to 3 mass %, more preferably 0 to 1 mass %, based on the total amount of the composition. In one embodiment, the aqueous composition does not contain any other surfactant.

[0047] (e3) Aqueous components other than water The aqueous composition may contain aqueous components other than (c) water and (d) polyol. The aqueous components form the external phase of the composition.

[0048] Examples of the aqueous components that can be used include wetting agents, natural polymers, synthetic polymers, preservatives, lower monoalcohols, etc. These may be used alone or in combination of two or more. The aqueous component does not include surfactants (the above (b) surfactants having a sterol skeleton and (e2) other surfactants).

[0049] The humectant is not particularly limited, but examples thereof include sugars such as sorbitol, mannitol, glucose, xylitol, maltitol, and trehalose; amino acids such as arginine, proline, serine, lysine HCl, threonine, valine, leucine, histidine, alanine, glycine, and carnosine; sodium pyrrolidone carboxylate, betaine, urea, sodium lactate, plant extracts, and seaweed extracts.

[0050] Other aqueous components that may be used include, but are not limited to, natural polymers such as guar gum, carrageenan, xanthan gum, sodium hyaluronate, pullulan, agar, and alginates; synthetic polymers such as hydroxyethyl cellulose, hydroxymethyl cellulose, carboxyvinyl polymer, polyacrylates, polyvinyl alcohol, and acrylic acid / alkyl methacrylate copolymers; and preservatives.

[0051] The aqueous component may contain a lower monoalcohol, for example, a primary alcohol having 1 to 5 carbon atoms, preferably ethanol. The content of the lower monoalcohol as the aqueous component is preferably small from the viewpoint of safety. The content of the lower monoalcohol is preferably 0 to 5% by mass, more preferably 0 to 3% by mass, and further preferably 0 to 1% by mass, based on the total amount of the composition. In one embodiment, the aqueous composition does not contain a lower monoalcohol. In addition, when a lower monoalcohol is contained, the mass ratio of the lower monoalcohol to (c) water (lower monoalcohol / water) is preferably 0.3 or less, more preferably 0.2 or less, and even more preferably 0.1 or less.

[0052] In addition, raw materials may be selected as necessary to prepare the aqueous composition. In addition to the above components, the aqueous composition may contain any components contained in ordinary cosmetics, quasi-drugs, or pharmaceuticals. For example, it may contain moisturizing agents, antioxidants, UV absorbers, thickeners, pH adjusters, powder components, metal sequestering agents, coloring materials, various skin nutrients, drugs, etc., as necessary.

[0053] (composition ratio) In the aqueous composition, the mass ratio [(b) / (a)] of (b) surfactant having a sterol skeleton to (a) cholesterol is 3 or more. If the (b) / (a) ratio is less than 3, cholesterol may precipitate in the aqueous composition (concentrate or dilute solution), resulting in reduced transparency. The upper limit of the (b) / (a) ratio is not particularly limited, but considering the feeling of use, low irritation to the skin, and cost, it is more preferable that it is a certain value or less, for example, 10 or less is preferable, 9 or less is more preferable, 8 or less is even more preferable, 7 or less is even more preferable, and 6 or less is particularly preferable. In some embodiments, the (b) / (a) ratio is preferably 3-10, more preferably 3-9, even more preferably 3-8, even more preferably 3-7, and particularly preferably 3-6.

[0054] In the aqueous composition, the mass ratio of the first polyol (d1) to cholesterol (a) [(d1) / (a)] is 3 or more. If the (d1) / (a) ratio is less than 3, cholesterol may precipitate in the aqueous composition (concentrate or dilute solution), resulting in reduced stability. From the viewpoint of improving transparency and long-term stability, the (d1) / (a) ratio is preferably 4 or more. The upper limit of the (d1) / (a) ratio is not particularly limited, but from the viewpoint of usability, it is preferably 10 or less, more preferably 8 or less, and particularly preferably 6 or less. In some embodiments, the (d1) / (a) ratio is preferably 3-10, more preferably 3-8, further preferably 4-8, and particularly preferably 4-6.

[0055] In the aqueous composition, the mass ratio of the second polyol (d2) to cholesterol (a) [(d2) / (a)] is 3 or more. If the (d2) / (a) ratio is less than 3, cholesterol may precipitate in the aqueous composition (concentrate or dilute solution), resulting in reduced stability. From the viewpoint of improving transparency and long-term stability, the (d2) / (a) ratio is preferably 4 or more. The upper limit of the (d2) / (a) ratio is not particularly limited, but from the viewpoint of usability, it is preferably 10 or less, more preferably 8 or less, and particularly preferably 6 or less. In some embodiments, the (d2) / (a) ratio is preferably 3-10, more preferably 3-8, further preferably 4-8, and particularly preferably 4-6.

[0056] In the aqueous composition, the mass ratio of (c) water to (a) cholesterol in the concentrated solution [(c) / (a)] is preferably 3 to 11. If the (c) / (a) ratio is 3 or more, cholesterol precipitation and cloudiness can be suppressed. The (c) / (a) ratio is more preferably 5 or more, further preferably 8 or more, and particularly preferably 9 or more. There is no particular upper limit to the (c) / (a) ratio, but from the viewpoint of improving production efficiency by reducing the amount of the composition to be subjected to high-pressure emulsification treatment while incorporating a sufficient amount of cholesterol, a ratio of 11 or less is preferred. In the aqueous composition, the (c) / (a) ratio in the diluent is not particularly limited, and may be appropriately adjusted to obtain a desired cholesterol ratio.

[0057] (Method of producing aqueous composition) The aqueous composition can be prepared according to a conventional method. For example, (a) an oily component containing cholesterol and, if necessary, (e1) other oily components, (b) a surfactant having a sterol skeleton and, if necessary, (e2) other surfactants, and (c) an aqueous component containing water, (d) a polyol and, if necessary, (e3) other aqueous components, may be mixed by stirring in an appropriate order, heated as necessary, and homogenized.

[0058] (Production method using high pressure emulsification) Another aspect of the present invention relates to a method for producing an aqueous composition containing cholesterol using a high-pressure emulsification treatment. The production method of this aspect includes the following steps (I) and (II). The production method of this aspect may further include the following step (III). Step (I): A step of preparing a solution containing (a) cholesterol, (b) a surfactant having a sterol skeleton, (c1) water, and (d) a polyol. Step (II): A step of subjecting the solution to a high-pressure emulsification treatment to obtain a concentrated solution in which cholesterol is dispersed within the solution. Step (III): A step of mixing the concentrate obtained in step (II) with (c2) water to obtain a diluted solution.

[0059] In the production method of this embodiment, the mass ratio [(b) / (a)] of the (b) surfactant having a sterol skeleton to the (a) cholesterol is 3 or more, the (d) polyol includes (d1) a first polyol which is a diol having 5 to 10 carbon atoms, and (d2) a second polyol which is at least one of a diol having 4 or less carbon atoms and glycerol, the mass ratio [(d1) / (a)] of the (d1) first polyol to the (a) cholesterol is 3 to 10, and the mass ratio [(d2) / (a)] of the (d2) second polyol to the (a) cholesterol is 3 to 10. By subjecting a solution in which (a) cholesterol is mixed with (b) a surfactant having a sterol skeleton at a specific (b) / (a) ratio to high-pressure emulsification, (a) cholesterol can be stably dispersed in an aqueous medium containing water, and a transparent aqueous composition can be obtained. Although cholesterol is a substance that easily crystallizes, it is presumed that in this method, cholesterol is dispersed at the molecular level by high-pressure emulsification, making it possible to stably dissolve cholesterol in an active agent or polyol, thereby suppressing the crystallization of cholesterol. However, the present invention is not limited to such a mechanism. Each step in the manufacturing method of this embodiment will be described below.

[0060] (1) Step (I): Solution preparation step The production method of this embodiment includes a step (I) of preparing a solution containing (a) cholesterol, (b) a surfactant having a sterol skeleton, (c1) water, and (d) a polyol.

[0061] There are no particular limitations on the method for mixing the components, and the components may be mixed by stirring in an appropriate order, heated as necessary, and homogenized.

[0062] The mixing temperature is preferably 80° C. or higher in order to enhance the solubility of cholesterol. In some embodiments, step (I) includes mixing (a) cholesterol, (b) a surfactant having a sterol skeleton, (c1) water, and (d) a polyol at a temperature of 80 to 90°C. By mixing at a temperature of 80°C or higher, (a) cholesterol can be quickly and stably dispersed in water. The upper limit of the mixing temperature is not particularly limited, but a temperature of 90°C or lower is preferable. The mixing temperature is more preferably 80 to 85°C.

[0063] When (e1) other oil components, (e2) surfactants containing other surfactants, and (e3) other aqueous components are blended, in step (I), these additive components are added to (a) cholesterol, (b) surfactant having a sterol skeleton, (c1) water, and (d) polyol, and mixed, and if necessary, heated and homogenized.

[0064] (2) Step (II): High-pressure emulsification process The manufacturing method of this embodiment includes, after step (I), step (II) of subjecting the solution obtained in step (I) to high-pressure emulsification to obtain a concentrated solution in which cholesterol is dispersed in the solution. The high-pressure emulsification produces an aqueous composition with excellent transparency in which cholesterol-containing oil phase components (oil droplets) are stably dispersed in the aqueous phase components.

[0065] The high-pressure emulsification treatment can be carried out, for example, using a high-pressure emulsifier. Examples of such machines include chamber-type high-pressure homogenizers such as Microfluidizer, Nanomizer, and Starburst; homogenous valve-type high-pressure homogenizers such as Gaulin-type homogenizer, Lanier-type homogenizer, high-pressure homogenizer, homogenizer, high-pressure homogenizer, and ultra-high-pressure homogenizer. Among these, chamber-type high-pressure homogenizers such as Microfluidizer, Nanomizer, and Starburst are preferred, and Microfluidizer and Nanomizer are more preferred, in that they suppress the generation of bubbles and facilitate stirring.

[0066] The high-pressure emulsification treatment is preferably carried out at a pressure of 100 to 200 MPa, and is typically carried out by passing the liquid through the mixture 1 to 3 times at a pressure of 100 to 200 MPa. In some embodiments, a microfluidizer is used for the high-pressure emulsification treatment, and liquid is passed through the microfluidizer 1 to 3 times at a pressure of 100 to 180 MPa. In some embodiments, a Nanomizer is used for the high pressure emulsification treatment, and the liquid is passed through the Nanomizer 1 to 3 times at a pressure of 120 to 200 MPa.

[0067] The high-pressure emulsification treatment is preferably carried out under a temperature condition of 50 to 90° C. (more preferably 80 to 85° C.) By setting the temperature within this range, a concentrate with excellent stability in which cholesterol precipitation and cloudiness are suppressed can be obtained.

[0068] (3) Step (III): Dilution step The production method of this embodiment may further include, after step (II), a step (III) of mixing the concentrate obtained in step (II) with (c2) water to obtain a diluted solution. (c2) The amount of water to be added may be adjusted so as to obtain a desired cholesterol concentration. The mixing temperature is not particularly limited, and mixing is typically carried out at a temperature of 10 to 40° C. (more preferably 15 to 35° C., and even more preferably 20 to 30° C., for example, room temperature). The mixing means is not particularly limited.

[0069] (composition ratio) The mass ratio of (c1) water to (a) cholesterol [(c1) / (a)] is not particularly limited as long as cholesterol can be stably dispersed in water. The (c1) / (a) ratio varies depending on the high-pressure emulsification apparatus and processing conditions used in step (II), but is preferably in the range of 2 to 11. If the (c1) / (a) ratio is 2 or more, precipitation of cholesterol and cloudiness in the concentrated liquid can be suppressed. The (c1) / (a) ratio is more preferably 3 or more, even more preferably 5 or more, even more preferably 8 or more, and particularly preferably 9 or more. The upper limit of the (c1) / (a) ratio is not particularly limited, but it is preferably 11 or less. In some embodiments, the (c1) / (a) ratio is from 2 to 11, or from 3 to 11, or from 5 to 11, or from 8 to 11. In some embodiments, the (c1) / (a) ratio is from 2 to 8, or from 3 to 8, or from 5 to 8.

[0070] In some embodiments, a microfluidizer is used for the high-pressure emulsification treatment, and the mass ratio of the (c1) water to the (a) cholesterol [(c1) / (a)] is 3 to 11. In this embodiment, the (c1) / (a) ratio is preferably 3 to 8, and more preferably 5 to 8.

[0071] In some embodiments, a Nanomizer is used for the high-pressure emulsification treatment, and the mass ratio of (c1) water to (a) cholesterol [(c1) / (a)] is 3 to 11. In this embodiment, the (c1) / (a) ratio is preferably 5 to 11, and more preferably 8 to 11.

[0072] Other preferred aspects of each of the constituent components and the ratio (mass ratio) of each component are as explained above in the section "Aqueous composition."

[0073] The above-mentioned production method provides an aqueous composition in which (a) cholesterol is stably dispersed in an aqueous medium containing water by blending a small amount of (b) a surfactant.

[0074] (O / W type microemulsion) In some embodiments, the aqueous composition is in the form of an O / W type microemulsion. The aqueous composition in such a form can be produced, for example, by the production method through the high-pressure emulsification process as described above.

[0075] In this specification, the term "O / W type emulsion" refers to a state in which finely dispersed droplets of an oil phase (oil droplets) are surrounded by a surfactant, and the outer phase is a continuous aqueous phase, in which the aqueous component and the oil component are stably mixed by the action of the surfactant. More specifically, the aqueous composition is in a form in which an oil phase (dispersed phase, oil droplets) containing (a) cholesterol is dispersed in an aqueous phase (continuous phase) containing (c) water.

[0076] In some embodiments, the oil phase comprises (a) cholesterol, and the aqueous phase (continuous phase) comprises (c) water, (d1) a first polyol, and (d2) a second polyol, with a surfactant present at the interface between the oil phase and the aqueous phase to form a stable emulsion.

[0077] In some embodiments, the median diameter of the oil phase (oil droplets) in the aqueous composition is 50 to 210 nm, preferably 50 to 180 nm. By making the oil phase (oil droplets) have such a nanoscale size, the transparency and stability of the aqueous composition are improved. The median diameter of the oil phase (oil droplets) is more preferably 50 to 150 nm, even more preferably 50 to 100 nm, and particularly preferably 50 to 80 nm. In the present invention, the median diameter of the oil phase (oil droplets, emulsion) means the median diameter of the scattering intensity distribution obtained by dynamic light scattering (DLS) (particle diameter at 50% cumulative in the particle distribution based on the scattered light intensity; D50). The median diameter can be measured by the method described in the examples below.

[0078] In general, the median diameter of the oil phase (oil droplets) in an aqueous composition increases over time. In some embodiments, it is preferable to carry out the high-pressure emulsification process (step (II)) and the dilution process (step (III)) under conditions in which the median diameter of the oil phase (oil droplets) after the dilution process (step (III)) is preferably 100 nm or less, more preferably 75 nm or less, and even more preferably 70 nm or less. The lower limit of the median diameter of the oil phase (oil droplets) is not particularly limited, but is preferably, for example, 50 nm or more. The median diameter of the oil phase (oil droplets) may vary depending on the conditions and composition of the high-pressure emulsification process (e.g., the type and content of surfactants and polyols), the storage environment, etc. In some embodiments, it is preferable that the median diameter of the oil phase (oil droplets) in the aqueous composition is within the above range one day after the dilution step (step (III)).

[0079] In some embodiments, the aqueous composition has long-term (e.g., 6 months) stability. In some embodiments, the median diameter of the oil phase (oil droplets) in the aqueous composition is 50 to 210 nm (preferably 50 to 180 nm, more preferably 50 to 150 nm) 6 months after the high-pressure emulsification treatment.

[0080] (Dosage form / use) The aqueous composition of the present invention can be formulated into various dosage forms, including, but not limited to, mists, sprays, lotions, and the like.

[0081] The aqueous composition can be used as a cosmetic. Examples of the aqueous composition include skin care cosmetics such as lotion, milky lotion, cream, beauty essence, massage agent, pack agent, hand cream, body lotion, body cream, and sunscreen, finishing cosmetics such as foundation, eye shadow, eye liner, mascara, eyebrow, concealer, lipstick, and lip balm, and hair cosmetics such as hair mist, treatment, hair cream, hair shampoo, and hair rinse. Methods of use include using the composition on hands, fingers, or cotton, and impregnating nonwoven fabrics and the like.

[0082] The aqueous composition of the present invention is also suitable for use in quasi-drugs, pharmaceuticals, and the like. For example, the aqueous composition can be used as a skin external preparation. Examples of the aqueous composition include external liquid preparations, external gel preparations, cream preparations, ointments, liniments, lotions, poultices, plasters, sprays, aerosols, etc. The method of use can be the same as that of the above-mentioned cosmetics.

[0083] (characteristic) The aqueous composition of the present invention has excellent transparency. The aqueous composition has a light transmittance of preferably 40% or more at a wavelength of 700 nm, more preferably 60% or more, even more preferably 80% or more, and particularly preferably 90% or more. In some embodiments, the aqueous composition is free of cloudiness and sediment.

[0084] The aqueous composition of the present invention has excellent stability. The aqueous composition of the present invention has excellent long-term stability. In one embodiment, no cholesterol precipitate is observed in the aqueous composition after it is left to stand for one month at room temperature (e.g., 20 to 30° C., particularly 25° C.) after preparation.

[0085] In some embodiments, the aqueous composition (e.g., the diluted solution obtained in step (III)) has excellent stability. In one embodiment, no cholesterol precipitate is observed in the diluted solution immediately after preparation at room temperature (e.g., 20 to 30°C, particularly 25°C).

[0086] In some embodiments, the aqueous composition (e.g., the diluted solution obtained in step (III)) has excellent long-term stability. In one embodiment, no cholesterol precipitate is observed in the diluted solution after it is left at room temperature (e.g., 20 to 30° C., particularly 25° C.) for 30 days (preferably 60 days, more preferably 90 days) after preparation.

[0087] In some embodiments, the aqueous composition (e.g., the concentrate obtained in step (II)) has excellent stability. The stability of the concentrate also correlates with the stability of the aqueous composition (diluted solution) obtained after dilution in step (III). The concentrated solution having excellent stability is diluted to give a diluted solution having excellent stability. In one embodiment, no cholesterol precipitate is observed in the concentrate after it is allowed to stand at room temperature (eg, 20 to 30° C., particularly 25° C.) for one day after preparation.

[0088] In some embodiments, the concentrate obtained in step (II) has excellent long-term stability. In one embodiment, no cholesterol precipitate is observed in the concentrate after it is left to stand at room temperature (e.g., 20 to 30° C., particularly 25° C.) for 7 days (more preferably 14 days, even more preferably 21 days, particularly preferably 28 days) after preparation. EXAMPLES

[0089] The present invention will be described in more detail below with reference to examples. Not limited to this. The blending amount and content of each component in the table are converted to the pure amount, and are expressed as "mass %" unless otherwise specified.

[0090] <Preparation of Cosmetic Composition> Concentrates and dilutions (compositions obtained by diluting the concentrates) having the compositions shown in Tables 1 to 4 were prepared by the following procedure.

[0091] 1. Step (I): Solution preparation step First, the components other than purified water ((a) cholesterol, (b) surfactant, (d1) first polyol, (d2) second polyol) were mixed and heated to 85°C to dissolve cholesterol in the solution. (c1) purified water heated to 85°C was added to this and stirred with a stirrer to obtain a cholesterol solution.

[0092] 2. Step (II): High-pressure emulsification process Next, the cholesterol solution was subjected to high-pressure emulsification using a high-pressure emulsification machine, and then cooled to 35° C. to obtain a concentrated liquid (concentrate) in which cholesterol was dispersed in the solution. Regarding the "High-pressure emulsification type" item in Tables 1 to 4, "NM" indicates that high-pressure emulsification was performed using a Nanomizer as the high-pressure emulsification device, "MD" indicates that high-pressure emulsification was performed using a Microfluidizer as the high-pressure emulsification device, and "none" indicates that the high-pressure emulsification in step (II) was not performed. The high pressure emulsification treatment conditions are as follows.

[0093] (High pressure emulsification using Nanomizer: NM) Pressure: 150MPa Fluid passage: 1 time Processing temperature (solution temperature): 80℃

[0094] (High pressure emulsification using a microfluidizer: MD) Pressure: 100MPa Fluid passage: 1 time Processing temperature (solution temperature): 80℃

[0095] 3. Step (III): Dilution Step At a temperature of 25°C, (c2) purified water, (e2) preservative and pH additive were added to the concentrated liquid (conc), and the mixture was stirred to obtain a diluted liquid. In addition, for the evaluation of the <stability of the diluted solution> described below, a diluted solution was used which was prepared by carrying out the dilution step of step (III) above using the concentrate (0d concentrate) obtained immediately after step (II). In addition, for the evaluation of <Transparency of the diluted solution> and <Median diameter of the oil phase in the diluted solution>, a diluted solution prepared by carrying out the dilution step in step (III) above one day after obtaining the concentrate in step (II) (1d concentrate) was used.

[0096] <Composition ingredients> The components used in the preparation are as follows: In the following, POE represents a polyoxyethylene chain, and the number in parentheses following it represents the number of moles added.

[0097] (b) Surfactants with a sterol skeleton EMALEX CS-20 (Nihon Emulsion Co., Ltd.): Polyoxyethylene (POE20) cholesteryl ether (HLB: 12)

[0098] (d) Polyol (d1) First polyol PD: 1,2-pentanediol (d2) Second polyol BG: 1,3-butylene glycol ·PDO: 1,3-propanediol

[0099] The concentrates (concentrates obtained in step (II)) and diluted solutions (diluted compositions obtained in step (III)) of the Examples and Comparative Examples prepared above were evaluated for the stability of the concentrates, the stability of the diluted solutions, the transparency (transmittance) of the diluted solutions, and the median diameter of the oil phase of the diluted solutions, as described below. The results are shown in the table below.

[0100] <Concrete stability> The concentrate was allowed to stand for 28 days at 25° C. Immediately after preparation (0 d), 1 day later (1 d), 7 days later (7 d), 14 days later (14 d), 21 days later (21 d), and 28 days later (28 d), the concentrate was visually inspected for the presence or absence of sedimentation and cloudiness, and evaluated according to the following criteria. (Judgment criteria) 〇: No cloudiness or sediment △: Slight cloudiness or sediment ×: Cloudy or sediment present

[0101] <Stability of dilution solution> The diluted solution (diluted solution of 0d concentrate) was allowed to stand for 28 days at 25° C. The presence or absence of sediment was visually confirmed for the composition immediately after dilution (0d), after 30 days (30d), after 60 days (60d), and after 90 days (90d), and evaluated according to the following criteria. (Judgment criteria) ○: No sediment ×: Sediment present

[0102] <Transparency of diluted solution: Transmittance at a wavelength of 700 nm> The transmittance of the diluted solution (diluted solution of 1d concentrate) at a wavelength of 700 nm was measured at 25°C using an ultraviolet-visible spectrophotometer (UV-2700 (light source wavelength 700 nm)). The measurement was performed three times and the average value was calculated (n=3). Note that, when sedimentation was confirmed in the composition, the composition was stirred immediately before the transmittance measurement. Note that the transmittance is a relative value (%) calculated by setting the transmittance of purified water as a control at 100%.

[0103] <Median diameter of oil phase in diluent> The particle diameter (median diameter (D50)) of the oil phase (oil droplets) in the diluted solution (diluted solution of 1d concentration) was measured at 25°C using a particle analyzer Litesizer500 (manufactured by Anton Paar) based on the cumulative 50% particle distribution of the scattered light intensity standard by dynamic light scattering (DLS). The measurement was performed three times and the average value was calculated.

[0104] [Table 1] [Table 2] [Table 3] [Table 4]

[0105] <Result> As shown in Tables 1 to 4, it has been confirmed that by blending (a) cholesterol with (b) a surfactant having a sterol skeleton, (d1) a first polyol, and (d2) a second polyol in specific ratios (the (b) / (a) ratio, the (d1) / (a) ratio, and the (d2) / (a) ratio), cholesterol can be stably dispersed in an aqueous medium containing water, and an aqueous composition (concentrate and dilution) with excellent transparency can be obtained.

[0106] As shown in Table 4, when high-pressure emulsification was performed with the same composition (No. 4-1, 4-3), the median diameter of the oil phase was smaller one day after preparation (1d) compared to when high-pressure emulsification was not performed (No. 4-2, 4-4), and it was confirmed that the concentrate and dilution solution had excellent long-term stability. It was shown that high-pressure emulsification can form a stable emulsion with a small oil phase median diameter, improving the long-term stability of the concentrate and dilution solution.

[0107] As shown in Table 1, when the (d1) / (a) ratio is 4 or more, a concentrate with excellent stability is obtained in which turbidity and cholesterol sedimentation are suppressed for a long period of time, and it was confirmed that the long-term stability of the concentrate is improved. Furthermore, the diluted solution also had excellent transparency, and even as of June, the median diameter of the oil phase was 180 nm or less, indicating excellent long-term stability.

[0108] As shown in Table 2, in the high-pressure emulsification process using the Nanomizer, No. 2-7 to 2-9, which have a (c1) / (a) ratio of 5, No. 2-4 to 2-6, which have a (c1) / (a) ratio of 8, and No. 2-1 to 2-3, which have a (c1) / (a) ratio of 11, have improved long-term stability of the concentrate compared to No. 2-10 to 2-12, which have a (c1) / (a) ratio of 2.

[0109] As shown in Table 3, in the high-pressure emulsification treatment using a microfluidizer, it was confirmed that Nos. 3-3, 3-8, and 3-9, which have a (c1) / (a) ratio of 5, and Nos. 3-2, 3-6, and 3-7, which have a (c1) / (a) ratio of 8, have improved long-term stability of the concentrate compared to Nos. 3-1, 3-4, and 3-5, which have a (c1) / (a) ratio of 11.

[0110] On the other hand, as shown in Table 1, in the cases where (d2) the second polyol was not included (No. 1-1), (d1) the first polyol was not included (No. 1-10), (d1) the amount of the first polyol was small (Nos. 1-2, 1-3, 1-6, 1-7, 1-11, 1-12, 1-15, 1-16), and (d2) the amount of the second polyol was small (Nos. 1-15 to 1-17), turbidity and cholesterol precipitates were observed one day after the formation of the concentrate, and the transparency of the diluted solution was also poor.

[0111] As shown in Table 4, (c1) when high-pressure emulsification was performed without adding water (Nos. 4-5 and 4-6), a stable concentrate was not obtained.

[0112] The above results show that by mixing cholesterol with a specific surfactant and polyol in a specific ratio, an aqueous composition (concentrate / dilution) with excellent stability and transparency can be obtained. In particular, by performing high-pressure emulsification, an aqueous composition (concentrate / dilution) with even greater stability and transparency can be obtained. Although the structure of the agent does not change due to high-pressure emulsification, it is believed that the cholesterol crystals contained in the agent are dispersed at the molecular level. In addition, cholesterol is a substance that easily crystallizes, but by dispersing it at the molecular level through high-pressure treatment, it can be stably dissolved in the surfactant and polyol, and it is believed that the crystallization of cholesterol is prevented.

[0113] Although the preferred embodiments and examples of the present invention have been described above, the present invention is not limited to these. Addition, omission, substitution, and other modifications of the configuration are possible without departing from the spirit of the present invention. [Industrial Applicability]

[0114] The composition of the present invention inhibits cholesterol precipitation and enables cholesterol to be stably incorporated into an aqueous component, and can be suitably used as cosmetics, quasi-drugs, pharmaceuticals, and the like (e.g., cosmetics and topical skin preparations).

Claims

1. 1. A method for producing an aqueous composition containing cholesterol, comprising the steps of: A step (I) of preparing a solution containing (a) cholesterol, (b) a surfactant having a sterol skeleton, (c1) water, and (d) a polyol; A step (II) of subjecting the solution to a high-pressure emulsification treatment to obtain a concentrated solution in which cholesterol is dispersed; Including, the mass ratio of the (b) surfactant having a sterol skeleton to the (a) cholesterol [(b) / (a)] is 3 or more; The (d) polyol includes (d1) a first polyol which is a diol having 5 to 10 carbon atoms, and (d2) a second polyol which is at least one of a diol having 4 or less carbon atoms and glycerol, a mass ratio of the (d1) first polyol to the (a) cholesterol [(d1) / (a)] is 3 to 10; The method, wherein the mass ratio [(d2) / (a)] of the second polyol (d2) to the cholesterol (a) is 3 to 10.

2. 2. The method according to claim 1, wherein the mass ratio of (c1) water to (a) cholesterol [(c1) / (a)] is 2 to 11.

3. The method according to claim 1, wherein the processing pressure in the high-pressure emulsification treatment is 100 to 200 MPa.

4. The method according to claim 1, wherein in the step (II), a high-pressure emulsifier selected from a Microfluidizer, a Nanomizer, and a Starburst is used for the high-pressure emulsification treatment.

5. In the step (II), a microfluidizer is used for the high-pressure emulsification treatment, The mass ratio of (c1) water to (a) cholesterol [(c) / (a)] is 3 to 11; or In the step (II), a Nanomizer is used for the high-pressure emulsification treatment, The method according to claim 4, wherein the mass ratio of (c1) water to (a) cholesterol [(c) / (a)] is 5 to 11.

6. The method according to claim 1, further comprising a step (III) of mixing the concentrated solution obtained in the step (II) with (c2) water to obtain a diluted solution.

7. The method according to claim 1, wherein (b) the surfactant having a sterol skeleton comprises at least one of polyoxyethylene cholesteryl ether and polyoxyethylene phytosteryl ether.

8. 2. The method of claim 1, wherein the (d) polyol comprises a first polyol that is a pentanediol and a second polyol selected from butylene glycol and propanediol.

9. 1. An aqueous composition containing cholesterol, comprising: (a) cholesterol, (b) a surfactant having a sterol skeleton, (c) water, and (d) a polyol; the mass ratio of the (b) surfactant having a sterol skeleton to the (a) cholesterol [(b) / (a)] is 3 or more; The (d) polyol includes (d1) a first polyol which is a diol having 5 or more carbon atoms, and (d2) a second polyol which is at least one of a diol having 4 or less carbon atoms and glycerol, a mass ratio of the (d1) first polyol to the (a) cholesterol [(d1) / (a)] is 3 to 10; A composition, wherein the mass ratio [(d2) / (a)] of the second polyol (d2) to the cholesterol (a) is 3 to 10.

10. The composition is in the form of an O / W emulsion, The composition according to claim 9, wherein the median diameter of the oil phase is 50 to 210 nm.

11. The composition according to claim 9, which has a light transmittance of 80% or more at a wavelength of 700 nm.

12. The composition according to claim 9, wherein the content of the (a) cholesterol is 0.1 to 3% by mass based on the total amount of the composition.

13. The composition according to claim 9, which is a cosmetic or an external skin preparation.

14. The composition of claim 9 , wherein the dosage form is a mist, spray or lotion.

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