Method for producing azelaic acid particles, and external preparation for skin

Abstract

Provided is a method for producing azelaic acid particles, the method being characterized by comprising: a solution preparation step for preparing an azelaic acid solution in which azelaic acid is dissolved in a good solvent; a crystallization step for mixing the azelaic acid solution prepared in the solution preparation step with purified water serving as a poor solvent to precipitate crystals; and a drying step for drying the product obtained in the crystallization step in a stand-still state.

Description

Method for producing azelaic acid particles and topical skin preparation

[0001] The present invention relates to a method for producing azelaic acid particles and an external skin preparation. More specifically, the present invention relates to a method for producing azelaic acid particles having a specific shape and an external skin preparation containing the azelaic acid particles.

[0002] Azelaic acid is a saturated dicarboxylic acid and a white, finely powdered substance. Azelaic acid has the effects of suppressing excessive sebum secretion and anti-inflammatory effects, and is known to function as an active ingredient in the treatment of acne. In addition, azelaic acid is known to inhibit melanocyte activity, activate skin metabolism, and have antioxidant properties, making it an active ingredient in the treatment of skin pigmentation.

[0003] Therefore, compositions containing azelaic acid are used as external preparations (external skin preparations) to be applied to the skin.For example, Patent Document 1 discloses an acne treatment agent containing azelaic acid in a pharmaceutically acceptable carrier, the carrier being selected from cream, ointment, and lotion forms.In addition, Patent Document 2 discloses an external skin preparation containing azelaic acid, a liquid oil having a polar group in the molecule, water, and an emulsion-stabilizing component, emulsified by dispersing at least the liquid oil in water.

[0004] Japanese Patent Publication No. 57-134416 Japanese Patent Publication No. 2015-078167

[0005] As shown in Patent Documents 1 and 2, when a composition containing azelaic acid is prepared and used in various products, azelaic acid is commonly dispersed in various bases containing oil and / or water. Furthermore, azelaic acid is known to have efficacy for making skin look beautiful (e.g., whitening effect) in addition to treating affected skin areas, and is also highly useful as a cosmetic ingredient.

[0006] The various efficacy effects of azelaic acid are believed to be exerted through contact with or penetration into the skin. Furthermore, azelaic acid is known to be a substance with high safety to the human body, and formulations of compositions containing azelaic acid as an active ingredient require the incorporation of azelaic acid at a relatively high proportion (approximately 5 to 20% by mass). However, azelaic acid is known to have low solubility in water, and incorporating a high amount of azelaic acid into topical skin preparations raises concerns about negative effects on the finish upon application to the skin and handling during product manufacture and use. Specifically, this can result in a whitish, washed-out finish that disrupts the uniformity of skin tone, or a powdery finish with noticeable powder, resulting in an overall unnatural finish. Furthermore, there are concerns about a decrease in the slipperiness of azelaic acid or a decrease in adhesion of azelaic acid to the skin upon application to the skin surface. Furthermore, when azelaic acid is dispersed in a liquid, aggregation is likely to occur, resulting in low uniform dispersibility, and azelaic acid particles tend to aggregate and adhere to wall surfaces, which makes it difficult to smoothly transport the powder raw material when blended into a topical skin preparation, resulting in problems such as poor handleability during product manufacturing. Therefore, the azelaic acid to be blended into a topical skin preparation is required to not only improve contact efficiency with the skin during use, but also to exhibit positive performance in terms of finish and handling during product manufacturing and / or use.

[0007] Therefore, the object of the present invention is to provide a method for producing azelaic acid particles having a form suitable for application to the skin, and to provide an external skin preparation that uses these azelaic acid particles and can fully exert the various efficacy effects of azelaic acid without compromising the finish or ease of handling during product manufacture and / or use.

[0008] The present inventors have conducted extensive research into the above-mentioned problems and have found that azelaic acid particles having a shape suitable for application to the skin can be obtained by using azelaic acid (azelaic acid solution) as a raw material and carrying out crystallization and drying under specific conditions, and that the above-mentioned problems can be solved by incorporating shape-controlled azelaic acid particles into a topical skin preparation, thereby completing the present invention. That is, the present invention encompasses the subject matter of the method for producing azelaic acid particles and the topical skin preparation described in the following sections.

[0009] Item 1. A method for producing azelaic acid particles, comprising: a solution preparation step of preparing an azelaic acid solution in which azelaic acid is dissolved in a good solvent; a crystallization step of mixing the azelaic acid solution prepared in the solution preparation step with purified water as a poor solvent to precipitate crystals; and a drying step of drying the product obtained in the crystallization step in a stationary state.

[0010] Item 2. The method for producing azelaic acid particles according to Item 1, wherein the temperature of the poor solvent is 0° C. or higher and 25° C. or lower.

[0011] Item 3. The method for producing azelaic acid particles according to Item 1 or 2, wherein the crystallization step includes a step of mixing the azelaic acid solution and the poor solvent and then allowing the mixture to stand for 6 hours or more.

[0012] Item 4. A skin topical preparation containing azelaic acid particles, wherein the azelaic acid particles are prepared by the method for producing azelaic acid particles according to Item 1 or 2.

[0013] Item 5. The method according to Item 4, wherein the dosage form of the topical skin preparation is such that the azelaic acid particles are insoluble in water. Item 6. A topical skin preparation containing azelaic acid particles having a plate-like structure and a median diameter of 10 μm or more as measured using a particle size distribution measuring device based on a laser diffraction scattering method.

[0014] According to the present invention, in addition to providing a method for producing azelaic acid particles having a form suitable for application to the skin, it is also possible to provide an external skin preparation that uses these azelaic acid particles and can fully exert the various efficacy effects of azelaic acid without compromising the finish or ease of handling during product manufacture and / or use.

[0015] 1 shows SEM images of commercially available azelaic acid. A. Observation magnification: 500x, B. Observation magnification: 1000x. This is a flow diagram of the method for producing azelaic acid particles of the present invention. These are SEM images (observation magnification: low magnification) of azelaic acid particles prepared by the method for producing azelaic acid particles of the present invention. A. Example 1, observation magnification: 25x, B. Example 2, observation magnification: 25x, C. Example 3, observation magnification: 25x, D. Example 4, observation magnification: 50x, E. Example 5, observation magnification: 25x, F. Comparative Example 1, observation magnification: 50x. These are SEM images (observation magnification: high magnification) of azelaic acid particles prepared by the method for producing azelaic acid particles of the present invention. A. Example 1, observation magnification: 200x, B. Example 2, observation magnification: 200x, C. Example 3, observation magnification: 250x, D. Example 4, observation magnification: 250x, E. Example 5, observation magnification: 250x. F. Comparative Example 1, observation magnification 300x. Images showing the results regarding the dispersibility of each azelaic acid particle in water. A. Azelaic acid particles prepared by the method for producing azelaic acid particles of the present invention (Example 4), B. Comparative azelaic acid (Comparative Example 2). Images showing the results regarding the finish after application of mixtures containing each azelaic acid particle. Left: A mixture of azelaic acid particles prepared by the method for producing azelaic acid particles of the present invention (Example 4) and petrolatum, Right: A mixture of azelaic acid (Comparative Example 2) and petrolatum as a comparative example.

[0016] As used herein, the singular forms include both the singular and the plural, unless otherwise specified herein or clearly contradictory in context. As used herein, the terms "comprise" and "include" are concepts that encompass "consist essentially of" and "consist only of." Hereinafter, embodiments of the method for producing azelaic acid particles and the topical skin preparation according to the present invention will be described, including the best mode.

[0017] [Production of Azelaic Acid Particles] The azelaic acid particles in the present invention refer to a substance obtained by granulating or granulating azelaic acid.

[0018] <Azelaic Acid> First, azelaic acid will be described. Azelaic acid (chemical formula C ９ H １６ O ４ ) is a saturated dicarboxylic acid and is a substance consisting of a white fine powder. Furthermore, the main industrial method for producing azelaic acid is known to be the ozonolysis of oleic acid. Here, as the raw material for the azelaic acid particles of the present invention, an azelaic acid solution in which azelaic acid is dissolved in a good solvent is used. However, the method for obtaining the azelaic acid itself is not particularly limited. A commercially available product may be used, or azelaic acid obtained by conventional synthesis may be used. Furthermore, a solution in which azelaic acid is dissolved obtained by conventional synthesis may be used as is as the raw material for the azelaic acid particles of the present invention.

[0019] FIG. 1 shows a scanning electron microscope (SEM) image of commercially available azelaic acid obtained by conventional methods. Note that FIG. 1A shows an observation magnification of 500x, and FIG. 1B shows an observation magnification of 1000x. The SEM image in FIG. 1 was obtained by using "Azelaic Acid" manufactured by CORUM Corporation as azelaic acid and a "TM4000Plus" scanning electron microscope manufactured by Hitachi High-Technologies Corporation at an accelerating voltage of 15 kV. From FIG. 1, it can be seen that commercially available azelaic acid contains needle-shaped, rod-shaped, spindle-shaped, and amorphous crystal structures, and is primarily composed of a fine powder of crystals having a needle-shaped structure with a length of approximately 1 to 30 μm and a width of 10 μm or less. Hereinafter, the needle-shaped, rod-shaped, spindle-shaped, and amorphous crystal structures of azelaic acid are collectively referred to as "structures such as needle-shaped structures." The particle size distribution of the azelaic acid crystals at this time was measured in a dry state using a particle size distribution measuring device ("PSA1190" manufactured by Anton Paar) based on a laser diffraction scattering method, and the median diameter (D50) was found to be approximately 5.4 μm.

[0020] The present inventors have found that azelaic acid obtained by conventional methods is a fine crystalline powder having a structure such as a needle-like structure, as shown in Figure 1, and have therefore discovered that when azelaic acid is used as an active ingredient in a topical skin preparation, the negative effects on the finish when applied to the skin and on handling during product manufacture and use are related to the azelaic acid being a fine powder and having a structure such as a needle-like structure.The present inventors have also found that by using azelaic acid (azelaic acid solution) as a raw material and producing azelaic acid particles under specific conditions, it is possible to control the shape of the azelaic acid particles and obtain azelaic acid particles suitable for application to the skin, and have arrived at the configuration of the present invention.

[0021] <Method for Preparing Azelaic Acid Particles> The method for producing azelaic acid particles according to the present invention uses an azelaic acid solution as a starting material and granulates azelaic acid under specific conditions and steps. Figure 2 is a flow chart showing the steps involved in the method for producing azelaic acid particles according to the present invention. As shown in Figure 2, the method for producing azelaic acid particles according to the present invention includes a solution preparation step 10 for preparing an azelaic acid solution, a crystallization step 20 for precipitating crystals from the azelaic acid solution prepared in the solution preparation step, and a drying step 30 for drying the product that has undergone the crystallization step. Each step will be described below.

[0022] The solution preparation step 10 is for obtaining an azelaic acid solution as a raw material, and more specifically, for preparing an azelaic acid solution in which azelaic acid 14 is dissolved in a good solvent 12. Here, the good solvent 12 may be any solvent that can dissolve a predetermined amount of azelaic acid 14 to prepare an azelaic acid solution, and specific examples of the good solvent include polar organic solvents such as alcohols such as ethanol and methanol, glycols such as propylene glycol and butylene glycol, and acetone.

[0023] As an example of the solution preparation step, as shown in Figure 2, azelaic acid 14, which is a fine powder and has a needle-like structure, is added to a container containing a good solvent 12 at room temperature or heated, and then the mixture is heated and stirred to form a solution (reference numeral 16), thereby preparing an azelaic acid solution 18. Hereinafter, "azelaic acid, which is a fine powder and has a needle-like structure," such as the commercially available azelaic acid shown in Figure 1, will also be referred to as "azelaic acid before dissolution" or "azelaic acid (powder)." Furthermore, the solution preparation step 10 is not limited to that shown in Figure 2. Another example of the solution preparation step 10 is to use an azelaic acid-containing solution produced in the process of synthesizing azelaic acid as is as the azelaic acid solution.

[0024] In the crystallization step 20, the azelaic acid solution 18 prepared in the solution preparation step 10 is mixed with purified water 22 as a poor solvent to precipitate crystals. The purified water used as the poor solvent 22 may be any water with a reduced impurity content, such as ultrapure water or pure water. From the viewpoint of production costs, preferred examples of purified water include ion-exchanged water, RO water, and distilled water.

[0025] One example of the crystallization step 20 is to add a poor solvent, i.e., purified water 22, to a container containing an azelaic acid solution at a predetermined amount and a predetermined rate, and then stir or allow to stand for a predetermined period of time to precipitate crystals (reference numeral 24). Another example of the crystallization step 20 is to add a poor solvent, i.e., purified water 22, to a container containing the poor solvent, i.e., purified water 22, at a predetermined amount and a predetermined rate, and then stir or allow to stand for a predetermined period of time to precipitate crystals (reference numeral 24). As a result, the azelaic acid solution becomes a slurry containing azelaic acid crystals.

[0026] Here, the shape of the obtained azelaic acid particles can be controlled by selecting various conditions (including operation details) related to the crystallization step 20. Hereinafter, conditions related to the shape control of the azelaic acid particles in the crystallization step 20 of the present invention will be described with examples.

[0027] The temperature in the crystallization step 20 of the present invention is not particularly limited. However, as shown in the examples below, by setting the poor solvent within a specific temperature range, the shape of the azelaic acid particles can be controlled, thereby obtaining azelaic acid particles with a morphology more suitable for application to the skin. Specifically, by setting the temperature range of the poor solvent used in the crystallization step 20 to 0°C or higher and 25°C or lower, the ratio of the long side to the short side of the plate-like structure (hereinafter referred to as the "aspect ratio") becomes small. In particular, by setting the temperature range of the poor solvent 22 used in the crystallization step 20 to 10°C or higher and 20°C or lower, the content of azelaic acid particles with a needle-like structure or azelaic acid particles with a large aspect ratio in the obtained azelaic acid particles is drastically reduced, making it possible to obtain azelaic acid particles with a morphology more suitable for application to the skin, more specifically, azelaic acid particles with a plate-like structure and a small aspect ratio, in high yield. The temperature of the poor solvent 22 may be selected so that the aspect ratio of the resulting azelaic acid particles is 10 or less, more preferably 5 or less. The aspect ratio preferably refers to the average aspect ratio. The average aspect ratio can be determined by measuring the long and short sides of each of a plurality of azelaic acid particles (preferably 20 or more, more preferably 50 or more) randomly selected under a microscope, calculating the aspect ratio of each azelaic acid particle, and averaging the measured values. This makes it possible to obtain azelaic acid particles that not only further improve the slipperiness when applied to the skin, but also further improve adhesion to the skin and reduce the appearance of a white cast.

[0028] Furthermore, the crystallization step 20 of the present invention involves mixing the azelaic acid solution 18 with purified water and then stirring or allowing the mixture to settle to precipitate crystals (reference numeral 24). The procedure and time for crystallization are not particularly limited, but as shown in the examples below, specific procedures and times can control the shape of the azelaic acid particles, resulting in azelaic acid particles with a form more suitable for application to the skin. Specifically, the crystallization step 20 includes allowing the mixture to settle for 6 hours or more, more preferably 12 hours or more, after mixing the azelaic acid solution 18 with purified water, thereby flattening the surface of the plate-like structure. This allows for further improved slipperiness when applied to the skin and also produces azelaic acid particles that can produce a glossy finish.

[0029] In the crystallization step 20, the amount of poor solvent 22 added relative to the azelaic acid solution 18 (addition ratio) is not particularly limited, but for example, the poor solvent 22 may be added in an amount at least two times, more preferably at least three times, the amount of poor solvent 22 added relative to the amount of azelaic acid solution 18. The mixing speed (time required for mixing) of the azelaic acid solution 18 and the poor solvent 22 is also not particularly limited, but may be set to 60 minutes or less, more preferably 30 minutes or less. This enables production with a high yield and stable quality.

[0030] The drying step 30 involves drying the product obtained in the crystallization step 20 in a static state (reference numeral 36), which causes aggregation and granulation of the azelaic acid, thereby obtaining azelaic acid particles 38. The drying of the product obtained in the crystallization step 20 may involve either directly drying the product or subjecting the product to further processing before drying.

[0031] In the drying step 30 of the present invention, it is sufficient that the material to be dried is in a stationary state during drying. The slurry 26 obtained in the crystallization step 20 may be directly used as the material to be dried. However, from the viewpoint of drying efficiency, it is preferable to use the solid content (reference numeral 34) obtained by solid-liquid separation (reference numeral 32) of the slurry 20 as the material to be dried, as also shown in FIG. 2 .

[0032] In the drying step 30 of the present invention, the means for drying in a stationary state is not particularly limited, but for example, the material to be dried (slurry or solid content) stored in a pallet may be dried using a known drying device. Examples of known drying devices include a cold air dryer, a hot air dryer, and a vacuum dryer. From the viewpoints of drying efficiency and suppressing denaturation of azelaic acid, it is preferable to use a vacuum dryer. More specifically, it is preferable to use a vacuum tray dryer.

[0033] In the drying step 30 of the present invention, the drying conditions such as the drying temperature and drying time are not particularly limited, but for example, when a vacuum dryer is used, drying can be carried out at 100°C or less for 36 hours or less. Furthermore, in the drying step of the present invention, the particle size obtained can be controlled by selecting and adjusting the drying conditions such as the drying temperature and drying time and the azelaic acid content in the material to be dried.

[0034] The amount of azelaic acid in the azelaic acid particles obtained by the method for producing azelaic acid particles according to the present invention is not particularly limited, but is preferably 90% by mass or more, more preferably 95% by mass or more, even more preferably 98% by mass or more, particularly preferably 99% by mass or more, for example, about 100% by mass.The azelaic acid particles obtained by the method for producing azelaic acid particles according to the present invention mainly have a plate-like structure.In the present invention, particles having a "plate-like structure" may be thin and flat, for example, particles having a plate-like or scale-like shape.The proportion of the number of azelaic acid particles having a plate-like structure to the total number of azelaic acid particles is, for example, 30% or more, 50% or more, 80% or more, or 90% or more.

[0035] The present inventors have found that azelaic acid particles have a specific shape, mainly a plate-like structure, and thus can be expected to have the function of improving the slipperiness on the skin surface compared to azelaic acid having a fine powder and a needle-like structure, and furthermore, can improve the adhesion of azelaic acid particles to the skin by approaching the skin ridges and reduce the feeling of white cast.In other words, the method for producing azelaic acid particles of the present invention makes it possible to obtain azelaic acid particles having a shape suitable for application to the skin.In addition, the azelaic acid particles obtained by the method for producing azelaic acid particles of the present invention have been used to evaluate the finish when applied to the skin and the handling properties during product production and / or use, and the results will be described below in the Examples.

[0036] [Topical Skin Preparation] The topical skin preparation of the present invention is a topical skin preparation containing azelaic acid particles, which are formulated with azelaic acid particles obtained by the above-described method for producing azelaic acid particles. This provides a topical skin preparation that is expected to provide improved slipperiness on the skin surface compared to preparations containing azelaic acid having a fine powder and a needle-like structure, etc., and that can improve adhesion to the skin by approaching the skin ridges and reduce the appearance of a white cast. This topical skin preparation can exhibit one or more of the efficacies of azelaic acid, including sebum suppression, anti-inflammatory effect, whitening effect, acne improvement, melanocyte activity inhibition, skin metabolism activation, antioxidant effect, and skin pigmentation inhibition, without compromising the finish or ease of use of the topical skin preparation. Furthermore, azelaic acid particles with excellent dispersibility in water (i.e., low coagulation tendency) can be used as a powder raw material, resulting in a topical skin preparation that is easy to handle during product manufacturing.

[0037] The azelaic acid particles incorporated into the topical skin preparation of the present invention may be azelaic acid particles having a specific shape, specifically, a plate-like structure, and the particle size is not particularly limited. For example, they may be a raw material size commonly used in powder cosmetics (median diameter D50 of approximately 5 μm to 20 μm), or may be larger than the fine powder of azelaic acid shown in FIG. 1 . The particle size of the azelaic acid particles in the present invention is preferably 10 μm or more, more preferably 25 μm or more, as determined, for example, by a median diameter (D50) measurement using a particle size distribution analyzer based on laser diffraction scattering. While there is no particular upper limit to the particle size of the azelaic acid particles, the median diameter (D50) is preferably 300 μm or less, more preferably 150 μm or less. By ensuring that the median diameter of the azelaic acid particles falls within the above range, the azelaic acid particles can be trapped in the skin grooves and remain there when applied to the skin, thereby achieving the effect of easily maintaining a state of adhesion without peeling off from the skin surface. This makes it possible to fully exert the various efficacy effects of azelaic acid while providing an excellent finish when applied to the skin.

[0038] In addition, the means for adjusting the particle size of the azelaic acid particles in the present invention is not particularly limited.For example, it can be selected the preparation conditions (solvent, processing time, processing temperature, etc.) when preparing azelaic acid particles from the azelaic acid solution as raw material, or can be subjected to crushing treatment and classification treatment such as sieving treatment for the prepared azelaic acid particles.Therefore, those skilled in the art can obtain azelaic acid particles that meet the desired size with ordinary skills.

[0039] In addition, the means for confirming (measuring) the particle size of the azelaic acid particles in the present invention is not particularly limited, and known measuring devices and measuring means can be used.For example, measurements using a particle size distribution measuring device or measurements using analysis (calculation) results based on image data can be mentioned.More specifically, in addition to the median diameter obtained using a particle size distribution measuring device based on laser diffraction scattering, the particle size of the azelaic acid particles in the present invention can also be the average value of the particle sizes (diameters, or a combination of the longest diameter and the shortest diameter) of multiple particles (for example, 20 particles) randomly selected from an SEM image of the azelaic acid particles.

[0040] In the topical skin preparation of the present invention, the amount of azelaic acid particles is not particularly limited, but is preferably 0.001 to 100.0% by mass. The lower limit is more preferably 0.1% by mass or more, even more preferably 1.0% by mass or more, and particularly preferably 5.0% by mass or more. The upper limit is more preferably 50.0% by mass or less, even more preferably 30% by mass or less, and particularly preferably 20.0% by mass or less. By being within the above range, the various efficacy effects of azelaic acid, such as sebum suppression effect, anti-inflammatory effect, and whitening effect, can be fully exhibited. Furthermore, from the viewpoint of fully exhibiting the various efficacy effects of azelaic acid when incorporated into a topical skin preparation and simultaneously achieving an excellent finish upon application to the skin, it is particularly preferable that the amount of azelaic acid particles be 5.0% by mass or more.

[0041] <Other Components> Depending on the intended use, the topical skin preparation of the present invention may contain one or more other components commonly used in general topical skin preparations, including cosmetics and therapeutic agents. Examples include inorganic pigments, polymer powders, oily raw materials, surfactants, moisturizers, thickeners, polymers, UV protection agents, antioxidants, antioxidant aids, sequestering agents, metallic soaps such as magnesium stearate, whitening agents, anti-wrinkle agents, agents for improving rough skin, anti-acne agents, deodorizing agents, refreshing agents, astringents, antibacterial agents, preservatives, pH adjusters, organic pigments, natural colorants, fragrances, vitamins, and emollients.

[0042] Examples of inorganic pigments include extender pigments, coloring pigments, and white pigments. Extender pigments are used to maintain the product's formulation, thereby adjusting the product's usability (spreadability, adhesion), gloss, etc. Specific examples include mica, sericite, talc, kaolin, synthetic phlogopite, calcium carbonate, magnesium carbonate, silicic anhydride, aluminum oxide, and barium sulfate. Coloring pigments adjust the color tone of the product, and specific examples include red iron oxide, yellow iron oxide, black iron oxide, chromium oxide, ultramarine, Prussian blue, and carbon black. White pigments not only adjust the color tone of the product, but also adjust the hiding power, and specific examples include titanium dioxide and zinc oxide.

[0043] Specific examples of polymer powders include polyethylene powder, polymethyl methacrylate powder, polyethylene terephthalate-polymethyl methacrylate laminate powder, nylon powder, polyurethane powder, and silicone powder.

[0044] Examples of oily raw materials include fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, and silicone oils. More specifically, examples of fats and oils include olive oil, camellia oil, macadamia nut oil, and castor oil; examples of waxes include carnauba wax, candelilla wax, jojoba oil, beeswax, and lanolin; examples of hydrocarbons include liquid paraffin, paraffin, petrolatum, ceresin, microcrystalline wax, and squalane; examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, and isostearic acid; examples of higher alcohols include cetyl alcohol, stearyl alcohol, isostearyl alcohol, and 2-octyldodecanol; examples of esters include isopropyl myristate, 2-octyldodecyl myristate, cetyl 2-ethylhexanoate, and diisostearyl malate; and examples of silicone oils include methylpolysiloxane, methylphenylpolysiloxane, decamethylcyclopentasiloxane, and highly polymerized methylpolysiloxane.

[0045] Examples of surfactants include anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants. More specifically, examples of anionic surfactants include higher fatty acid soaps, alkyl sulfate ester salts, polyoxyalkyl ether sulfate salts, acyl N-methyl taurine salts, alkyl ether phosphate ester salts, and N-acyl amino acid salts. Examples of cationic surfactants include alkyl trimethyl ammonium chloride, dialkyl dimethyl ammonium chloride, and benzalkonium chloride. Examples of amphoteric surfactants include alkyl dimethyl amino acetate betaine, alkyl amidopropyl dimethyl amino acetate betaine, and 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine. Examples of nonionic surfactants include polyoxyethylene surfactants, polyhydric alcohol esters, and ethylene oxide-propylene oxide block copolymers.

[0046] Examples of moisturizing agents include glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, sodium lactate, sodium 2-pyrrolidone-5-carboxylate, sodium hyaluronate, hydrolyzed hyaluronic acid, hydroxypropyltrimonium hyaluronate, sodium carboxymethyl hyaluronate, and ceramides (pseudoceramides, human ceramides, natural human ceramides).

[0047] Examples of thickeners include quince seed gum, xanthan gum, sodium carboxymethylcellulose, and carboxyvinyl polymer.

[0048] Examples of the polymer include polyvinyl alcohol, polyvinylpyrrolidone, nitrocellulose, and polymeric silicone.

[0049] Examples of ultraviolet protection agents include ultraviolet absorbers such as benzophenone derivatives, para-aminobenzoic acid derivatives, methoxycinnamic acid derivatives, and salicylic acid derivatives, and ultraviolet scattering agents such as fine particle titanium oxide, fine particle zinc oxide, and fine particle iron oxide.

[0050] Examples of antioxidants include tocopherol, BHT, gallic acid esters, etc. Examples of antioxidant aids include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, cephalin, hexametaphosphate, phytic acid, ethylenediaminetetraacetic acid (EDTA), etc.

[0051] Examples of sequestering agents include sodium ethylenediaminetetraacetate, phosphoric acid, citric acid, ascorbic acid, succinic acid, gluconic acid, sodium polyphosphate, and sodium metaphosphate.

[0052] Examples of whitening agents include vitamin C, arbutin, kojic acid, ellagic acid, and rucinol.

[0053] Examples of anti-wrinkle agents include retinoids (vitamin A), α-hydroxy acids, various peptides, amino acids, and the like.

[0054] Examples of the skin roughness improving agent include anti-inflammatory agents such as β-glycyrrhetinic acid, glycyrrhizinic acid derivatives, allantoin, azulene, and hydrocortisone, and protease inhibitors.

[0055] Examples of anti-acne medications include sebum-suppressing ingredients such as estradiol, estrone, ethinylestradiol, and vitamin B6; keratin-exfoliating and / or dissolving ingredients such as sulfur, salicylic acid, and resorcinol; bactericidal ingredients such as benzalkonium chloride, benzethonium chloride, halocarban, and 2,4,4-trichloro-2-hydroxyphenol; and anti-inflammatory ingredients such as glycyrrhizic acid and glycyrrhetinic acid.

[0056] Examples of deodorant agents include antiperspirant ingredients such as chlorohydroxyaluminum, aluminum chloride, allantoin chlorohydroxyaluminum, zinc oxide, zinc paraphenolsulfonate, and silver-containing zeolite; bactericidal ingredients such as benzalkonium chloride, isopropylmethylphenol, benzethonium chloride, halocarban, and chlorhexidine hydrochloride; deodorizing ingredients such as polyphenol-based persimmon tannin and tea catechin; and antioxidant ingredients such as thiotaurine, hypotaurine, and tocopherol.

[0057] Examples of the cooling agent include menthol and camphor.

[0058] Examples of astringents include zinc oxide, zinc sulfate, allantoin hydroxyaluminum, aluminum chloride, zinc sulfocarbonate, tannic acid, citric acid, and lactic acid.

[0059] Examples of antibacterial agents include benzoic acid and its salts, salicylic acid and its salts, phenol, sorbic acid and its salts, dehydroacetic acid and its salts, paraben, chlorcresol, hexachlorophene, resorcinol, isopropylmethylphenol, orthophenylphenol, benzalkonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, alkylisoquinolinium bromide, trichlorocarbanilide, halocarban, photosensitizer No. 201, phenoxyethanol, triclosan, methylchloroisothiazolinone-methylisothiazolinone solution, bisabolol, alkyldiaminoethylglycine hydrochloride, trichloro-salicylanilide, tribromo-salicylanilide, mercury-based compounds, formalin, white lime, bithionol, boric acid-borax, dichlorophen, hexachlorophene, and halogenated salicylanilide.

[0060] Examples of preservatives include methylparaben, ethylparaben, butylparaben, and phenoxyethanol.

[0061] Examples of pH adjusters include acids such as citric acid and tartaric acid, alkalis such as sodium hydroxide and potassium hydroxide, and buffers such as lactic acid-sodium lactate, citric acid-sodium citrate, and succinic acid-sodium succinate.

[0062] Other ingredients that can impart particularly beneficial functions to topical skin preparations may also be included, such as ingredients containing growth factors and / or cytokines that inhibit skin aging and damage and activate the production of skin tissue (e.g., human stem cell culture medium (supernatant)), and ingredients that promote collagen production (e.g., exosomes, hydroxyapatite).

[0063] Furthermore, other ingredients may be added depending on the formulation and product form of the topical skin preparation, which will be described later. For example, if the topical skin preparation is a product with a cleansing function, ingredients known as cleansing agents may be used, as well as scrubbing agents, water-soluble polymers, chelating agents, etc. Furthermore, if the topical skin preparation is a product that forms an emulsion, ingredients known as emulsifiers may be used.

[0064] <Dosage Form and Form of Topical Skin Preparation> The dosage form of the topical skin preparation of the present invention is not particularly limited, but is preferably one in which the azelaic acid particles described in this embodiment are incorporated while maintaining their shape. In other words, the dosage form of the topical skin preparation of the present invention is preferably one in which the azelaic acid particles are insoluble in water. One example of the dosage form of the topical skin preparation of the present invention is one in which the entire composition constituting the topical skin preparation is composed of solid components. More specifically, this includes a solid form in which the entire composition is compressed (e.g., pressed powder) or a powder form in which the composition is used in powder form (e.g., loose powder). Another example is one in which the composition constituting the topical skin preparation is in a state in which the azelaic acid particles are dispersed in various dispersion media without dissolving. More specifically, this includes a gas-solid type (e.g., aerosols composed of a propellant gas and powder), a liquid-solid type (e.g., a liquid layer and a powder layer), a water-in-oil (W / O) type, an oil-in-water (O / W) type, and a multi-layer type (W / O / W, O / W / O) type. In addition, from the viewpoint of maintaining the shape of azelaic acid particles, the dosage form of the external preparation for skin of the present invention is particularly preferably solid or powder.Here, when the dosage form of the external preparation for skin of the present invention is an emulsion such as water-in-oil (W / O) type, oil-in-water (O / W) type, or multi-layer (W / O / W, O / W / O) type, the emulsification method for producing the emulsion is not particularly limited.Examples of the emulsification method include, for example, surface chemical method using emulsifier (surfactant) or mechanical method by stirring, as well as phase inversion emulsification, liquid crystal emulsification, amino acid gel emulsification, D-phase emulsification, three-phase emulsification, etc.

[0065] Furthermore, the form of the product related to the topical skin preparation of the present invention is not particularly limited, and examples thereof include foundations (powder type, liquid type, cream type, cushion type), control colors (powder type, liquid type, cream type), base powders, finishing powders (face powders), carmine lotion, BB cream, CC cream, emulsions (emollient lotions, massage lotions, etc.), emollient creams, massage creams, mist lotions, sunscreens, antiperspirants (roll-on type, stick type, aerosol type), facial cleansers, body soaps, hand soaps, solid soaps, shampoos (including dry shampoos), rinses, conditioners, hair packs, and scalp cosmetics (liquid type, cream type, aerosol type).

[0066] Furthermore, the topical skin preparation of the present invention is preferably in a dosage form and product form suitable for direct application to the skin.In other words, the topical skin preparation of the present invention is preferably in a dosage form and product form suitable for application to the skin before using other topical skin preparations (e.g., other cosmetics) or after washing or face washing.This makes it possible to more effectively demonstrate the beneficial effects of azelaic acid contained in the topical skin preparation of the present invention.In particular, by using azelaic acid in topical skin preparations (powder cosmetics, etc.) whose main constituent is powder, the contact efficiency of azelaic acid with the skin is improved, and it is expected that the beneficial effects of azelaic acid as a cosmetic ingredient can be more effectively demonstrated.

[0067] [Method for producing topical skin preparation] The topical skin preparation of the present invention can be produced by mixing azelaic acid particles and other ingredients by a conventional method (cosmetic composition) and filling the mixture into a container or molding it.

[0068] For example, when the topical skin preparation is a solid or powder cosmetic (powder cosmetic), a mixture (cosmetic composition) of azelaic acid particles and other ingredients mixed by a conventional method can be filled directly into a container and provided as a loose powder. Another example is to fill the cosmetic composition into a container and then provide it as a pressed powder using equipment commonly used in the production of topical skin preparations, such as a press or dryer.

[0069] Furthermore, when the topical skin preparation is a gas-solid or liquid-solid cosmetic, for example, a mixture (cosmetic composition) consisting of azelaic acid particles and other ingredients can be mixed with each dispersion medium (propellant gas or poor solvent as a liquid layer) by a conventional method and filled into a container to provide an aerosol cosmetic or a two-layer (liquid layer and powder layer) cosmetic. Furthermore, when the topical skin preparation is a water-in-oil (W / O) type, oil-in-water (O / W) type, or multi-layer (W / O / W, O / W / O) type cosmetic, for example, azelaic acid particles can be dispersed in an aqueous phase or an oil phase, mixed or emulsified with other ingredients by a conventional method, and filled into a container to provide a finished product. More specifically, for example, a stabilizer and an oil phase component can be added to the aqueous phase component in which the azelaic acid particles are dispersed, emulsified via a homomixer treatment, and filled into a container to provide a water-in-oil (W / O) cosmetic (such as a cream-type foundation or emulsion). The topical skin preparation of the present invention can be used in various cosmetics, quasi-drugs, and pharmaceuticals.

[0070] The present invention will be specifically described below with reference to examples, but the technical scope of the present invention is not limited to these examples.

[0071] [Preparation of Azelaic Acid Particles] First, the preparation of azelaic acid particles in this example will be described. In the solution preparation step, azelaic acid having a fine powder and a needle-like structure ("Azelaic Acid" manufactured by CORUM; azelaic acid in FIG. 1) was dissolved in 99% ethanol to prepare an azelaic acid solution. The amount of good solvent (ethanol) for azelaic acid was three or eight times that of azelaic acid. Next, in the crystallization step, purified water (ion-exchanged water) was added as a poor solvent to the azelaic acid solution to precipitate crystals, thereby obtaining an azelaic acid-containing slurry. The crystal precipitation procedure involved stirring for one hour, followed by leaving the mixture to stand for 12 hours or more, or continuously stirring for 12 hours or more. The amount of poor solvent added to the azelaic acid solution was three or four times that of the good solvent, and the rate of addition of the poor solvent to the azelaic acid solution (time required for mixing) was one minute or less. Then, in the drying step, the slurry was subjected to solid-liquid separation, and the obtained solid was placed on a stainless steel pallet and dried for 6 hours in a vacuum dryer to obtain azelaic acid particles.

[0072] The procedures and conditions for preparing azelaic acid particles in this example are shown in Table 1. Comparative Example 1 (in which tap water was used as the poor solvent) is also shown in Table 1. The particle size distribution of the azelaic acid particles obtained in each example and comparative example was measured in a dry state using a particle size distribution measuring device ("PSA1190" manufactured by Anton Paar) based on a laser diffraction scattering method, and is shown in Table 1 as the median diameter (D50).

[0073]

[0074] Figures 3 and 4 show SEM images of the azelaic acid particles obtained in Examples 1 to 5 and Comparative Example 1, taken under the same observation conditions as in Figure 1. Note that Figure 3 was taken at a low magnification (25x or 50x), while Figure 4 was taken at a high magnification (200x to 300x). Figures 3 and 4 show that in Examples 1 to 5 and Comparative Example 1, aggregation or granulation of the azelaic acid occurred, compared to the azelaic acid before dissolution (see Figure 1), and azelaic acid particles mainly having a plate-like structure were obtained.

[0075] Comparing Examples 1 to 5 with Comparative Example 1, it can be seen that the shape and size of the azelaic acid particles in Comparative Example 1 (F in Figure 3) vary considerably, whereas the shape and size of the azelaic acid particles in Examples 1 to 5 are relatively uniform (exist within a certain range) (A-E in Figure 3).

[0076] In particular, comparing Example 1 (FIG. 4A) with Example 2 (FIG. 4B) based on FIG. 4, it can be seen that the crystallization step involving standing during crystallization (Example 1) had a flatter surface in the plate-like structure than the crystallization step involving continuous stirring without standing during crystallization (Example 2). Furthermore, comparing Examples 3 to 5 (FIG. 4C to FIG. 4E) based on Table 1 and FIG. 4, it can be seen that as the temperature of the poor solvent decreases below 25°C, the aspect ratio of the plate-like structure decreases and the yield improves. Furthermore, as shown in Examples 4 and 5 (FIG. 4D and FIG. 4E), when the temperature of the poor solvent is 20°C or lower, the content of azelaic acid particles having a needle-like structure or azelaic acid particles with a large aspect ratio is drastically reduced, and only azelaic acid particles having a morphology more suitable for application to the skin (azelaic acid particles with a plate-like structure and a small aspect ratio) can be obtained in high yield.

[0077] In addition, it was found that in Examples 4 and 5, light reflection occurs on the particle surface due to the characteristics of the plate-like structure of the azelaic acid particles (small aspect ratio and flat surface).

[0078] [Evaluation of Azelaic Acid Particles] First, the obtained azelaic acid particles were evaluated for finish when applied to the skin. The example used for the evaluation was the azelaic acid particles of Example 4. In addition, in the evaluation, azelaic acid before being granulated (azelaic acid before being dissolved; see Figure 1) was used as a comparative example (Comparative Example 2).

[0079] The evaluation method will be described below. Ten panelists were asked to apply the azelaic acid particles of the Example (Example 4) and the azelaic acid of the Comparative Example (Comparative Example 2) to a part of the skin (inside the forearm), and a visual evaluation test was conducted from the viewpoints of "high adhesion to the skin," "powderyness of the finished product," "white cast feeling upon application," and "transparency of the finished product." The evaluation test was conducted by performing a relative evaluation of the Examples, with the Comparative Example being set as "0 (standard)." The evaluation criteria and evaluation results for each viewpoint are as follows:

[0080] (High Adhesion to Skin) The high adhesion to skin when the Examples were applied was visually evaluated relative to the Comparative Example. The evaluation criteria are as follows: 2: Very high (adhesion to skin compared to the Comparative Example) 1: High 0: Neither high nor low (same as the Comparative Example) -1: Low -2: Very low

[0081] Based on the above evaluation criteria, an evaluation test was conducted for each panelist, and the average of the obtained evaluation results was 2.00. In other words, it was found that the Example (azelaic acid particles having a specific shape) exhibited higher adhesion to the skin than the Comparative Example.

[0082] (Powderiness of finish) The powderiness of the finish when the Examples were applied was visually evaluated relative to that of the Comparative Example. The evaluation criteria are as follows: 2: Not powdery at all (compared to the Comparative Example) 1: Not powdery 0: Neither (same as the Comparative Example) -1: Powdery -2: Very powdery

[0083] Based on the above evaluation criteria, an evaluation test was conducted for each panelist, and the average of the obtained evaluation results was 2.00. In other words, it was found that the Examples did not exhibit a powdery finish compared to the Comparative Examples, and an excellent finish feeling was obtained.

[0084] (Feeling of white cast upon application) When the Examples were applied, the feeling of white cast against the skin color was visually evaluated relative to the feeling of white cast of the Comparative Example. The evaluation criteria were as follows: 2: No white cast at all (compared to the Comparative Example) 1: No white cast 0: Neither (same as the Comparative Example) -1: White cast -2: Very white cast

[0085] Based on the above evaluation criteria, an evaluation test was conducted for each panelist, and the average of the obtained evaluation results was 2.00. In other words, it was found that the Examples did not give off any white cast feeling when applied to the skin, as compared with the Comparative Examples, and an excellent finish feeling was obtained.

[0086] (Transparency of Finish) The transparency of the finish after application of the Examples was visually evaluated relative to the Comparative Example. The evaluation criteria are as follows: 2: Very transparent (compared to the Comparative Example) 1: Transparent 0: Neither transparent nor transparent (similar to the Comparative Example) -1: Not transparent -2: Not transparent at all Based on the above evaluation criteria, an evaluation test was conducted for each panelist, and the obtained evaluation results were averaged to obtain a score of 2.00. In other words, it was found that the Examples showed higher transparency in the finish after application to the skin than the Comparative Example, and an excellent finish feeling was obtained.

[0087] From the above evaluation results, the azelaic acid particles of the specific shape of the embodiment can improve adhesion when applied to the skin and reduce the feeling of white cast, compared with the azelaic acid of the comparative example having a needle-like structure, etc., and even when used in a high formulation amount (usage amount) as an active ingredient in a skin external preparation, it does not impair the finish when used.Furthermore, the azelaic acid particles of the embodiment maintain the properties of azelaic acid, so can fully exert the efficacy and effect that azelaic acid has.

[0088] Next, the resulting azelaic acid particles were evaluated for dispersibility (aggregation) in water. The example used for the evaluation was the azelaic acid particles of Example 4. The comparative example used for the evaluation was Comparative Example 2 (azelaic acid before dissolution; see FIG. 1 ).

[0089] The evaluation method is as follows: 9 g of purified water is placed in a 100 mL beaker, and 1 g of the azelaic acid particles of the Example or the azelaic acid of the Comparative Example is added thereto, followed by stirring for 120 seconds. Thereafter, the dispersion state of the azelaic acid particles of the Example and the azelaic acid of the Comparative Example in water is visually confirmed.

[0090] 5 is an image showing the results of evaluation of the dispersibility in water of the azelaic acid particles of Example (Example 4) and the azelaic acid of Comparative Example (Comparative Example 2). As shown in A of Fig. 5, it can be seen that the azelaic acid particles of Example (Example 4) are dispersed substantially uniformly in water. On the other hand, as shown in B of Fig. 5, it can be seen that the azelaic acid of Comparative Example (Comparative Example 2) aggregates in water, resulting in a decrease in dispersibility.

[0091] From the above evaluation results, it is found that the azelaic acid particles of the examples having a specific shape have better dispersibility in water, in other words, lower agglomeration tendency, compared with the azelaic acid particles of the comparative examples having a needle-like structure, etc. Furthermore, it is shown that by using the azelaic acid particles of the examples as a powder raw material for a skin external preparation, it is possible to provide a skin external preparation that is easy to handle during product manufacturing, even when used in a high amount (usage amount) as an active ingredient in the skin external preparation.

[0092] Next, the obtained azelaic acid particles were mixed with a versatile petrolatum as a base, and the mixture was evaluated for finish after application (particularly the degree of white cast). The example used for the evaluation was the azelaic acid particles of Example 4. The comparative example used for the evaluation was Comparative Example 2 (azelaic acid before dissolution; see Figure 1).

[0093] The evaluation method will be described below. 0.4 g of the azelaic acid particles of the example or the azelaic acid of the comparative example was kneaded into 1.6 g of white petrolatum (Y-445 manufactured by Nikko Rica Corporation), and 0.4 g of this mixture was applied to a sample having a predetermined area (5 × 2.7 cm ２The mixture after application is visually inspected to check the finish (white cast) of the azelaic acid particles of the example or the azelaic acid particles of the comparative example after application.

[0094] Fig. 6 is an image showing the results of evaluation of the finish after application of the mixture of azelaic acid particles and petrolatum of Example (Example 4) and the mixture of azelaic acid and petrolatum of Comparative Example (Comparative Example 2).As shown on the right side of Fig. 6, for the mixture of azelaic acid particles and petrolatum of Example (Example 4), the background color (black) is transmitted through the mixture after application, which shows that whitish appearance is suppressed and transparency is high.On the other hand, as shown on the left side of Fig. 6, for the mixture of azelaic acid and petrolatum of Comparative Example (Comparative Example 2), the background color (black) is hardly transmitted through the mixture after application, which shows that whitish appearance occurs.

[0095] From the above evaluation results, the azelaic acid particles of specific shape in Example can reduce the feeling of white cast when applied to skin, even when mixed with petrolatum, compared with the azelaic acid of comparative example having needle-like structure, and when the azelaic acid particles of Example are used as an active ingredient in a high amount (usage amount) of external skin preparation, they do not impair the finish when used.Furthermore, the azelaic acid particles of Example maintain the properties of azelaic acid, so they can fully exert the efficacy and effect that azelaic acid has.

[0096] [Formulation Examples] Examples of formulations for the external skin preparation of the present invention are shown below, however, the technical scope of the present invention is not limited to these formulation examples.

[0097] Formulation Example 1 A face powder (loose powder) was prepared according to the following formulation: Component name Amount (mass %) Azelaic acid particles 10.00 Talc 60.00 Sericite 20.00 Silica 5.00 Zinc myristate 5.00

[0098] (Formulation Example 2) A baby powder was prepared according to the following formulation: Component name Amount (mass %) Azelaic acid particles 20.00 Talc 73.00 Zinc oxide 3.00 Magnesium stearate 4.00 Fragrance appropriate amount

[0099] Formulation Example 3 A carmine lotion was prepared according to the following formulation: Component name Amount (mass %) Azelaic acid particles 3.00 Iron oxide 0.15 Zinc oxide 0.50 Kaolin 2.00 Ethanol 15.00 Glycerin 2.00 1,3-butylene glycol 0.15 Camphor 0.20 Phenol 0.02 Purified water 76.98

[0100] Formulation Example 4 A water-in-oil emulsion foundation (cream type) was prepared according to the following formulation: Component Amount (mass %) Azelaic acid particles 5.00 Sericite 3.36 Kaolin 3.00 Titanium dioxide 7.32 Red iron oxide 0.36 Yellow iron oxide 0.80 Black iron oxide 0.16 Liquid paraffin 5.00 Decamethylcyclopentanesiloxane 12.00 Polyoxyethylene-modified dimethylpolysiloxane 4.00 Purified water 51.90 1,3-butylene glycol 5.00 Dispersant 0.10 Stabilizer 2.00

[0101] Formulation Example 5 A solid powder foundation (cake-type foundation) was prepared according to the following formulation. Component Amount (mass %) Azelaic acid particles 10.00 Talc 33.10 Kaolin 15.00 Sericite 10.00 Zinc oxide 7.00 Titanium dioxide 3.80 Red iron oxide 1.00 Yellow iron oxide 2.90 Black iron oxide 0.20 Squalane 8.00 POE sorbitan monooleate 3.00 Isocetyl octanoate 2.00 Isostearic acid 4.00 Preservative / antioxidant Appropriate amount Fragrance Appropriate amount

[0102] Formulation Example 6 An emulsion (emollient lotion, water-in-oil type) was prepared according to the following formulation: Component Amount (mass %) Azelaic acid particles 5.00 Microcrystalline wax 1.00 Beeswax 2.00 Lanolin 2.00 Liquid paraffin 19.00 Squalane 9.00 Propylene glycol 7.00 Sorbitan sesquioleate 4.00 POE (20) sorbitan monooleate 1.00 Purified water 50.00 Preservative Appropriate amount Fragrance Appropriate amount

[0103] Formulation Example 7 An emollient cream (oil-in-water type) was prepared according to the following formulation: Component Amount (mass %) Azelaic acid particles 15.00 Stearyl alcohol 5.50 Stearic acid 1.00 Squalane 2.00 Octyldodecanol 8.50 1,3-butylene glycol 1.00 PEG 1500 4.00 POE (25) cetyl alcohol ether 3.00 Glycerin monostearate 2.00 Purified water 45.00 Preservative / antioxidant appropriate amount Fragrance appropriate amount

[0104] The method for producing azelaic acid particles of the present invention is used to provide azelaic acid particles that can utilize the various efficacy effects of azelaic acid without impairing the finish when applied to the skin or the handleability during product production and / or use. Furthermore, topical skin preparations containing azelaic acid particles produced by the method for producing azelaic acid particles of the present invention can be used in various cosmetics, quasi-drugs, and pharmaceuticals.

Claims

1. A method for producing azelaic acid particles, comprising: a solution preparation step of preparing an azelaic acid solution in which azelaic acid is dissolved in a good solvent; a crystallization step of mixing the azelaic acid solution prepared in the solution preparation step with purified water as a poor solvent to precipitate crystals; and a drying step of drying the product obtained in the crystallization step in a stationary state.

2. The method for producing azelaic acid particles according to claim 1, wherein the temperature of the poor solvent is from 0 to 25 degrees.

3. The method for producing azelaic acid particles according to claim 1 or 2, characterized in that the crystallization step includes a process of mixing the azelaic acid solution with the poor solvent and then leaving the mixture to stand for 6 hours or more.

4. A method for producing an external preparation for skin containing azelaic acid particles, comprising: preparing azelaic acid particles by the method for producing azelaic acid particles described in claim 1 or 2; and adding the azelaic acid particles as an ingredient of the external preparation for skin.

5. The method according to claim 4, wherein the formulation of the topical skin preparation is characterized in that the azelaic acid particles are in a water-insoluble state.

6. A skin preparation containing azelaic acid particles having a plate-like structure and a median diameter of 10 μm or more as measured using a particle size distribution measuring device based on a laser diffraction scattering method.

Images