Resin particle, and method for producing resin particle

Abstract

To provide resin particles which contain a biodegradable resin, and are excellent in adhesion to skin and soft use feeling on skin for a cosmetic.SOLUTION: Resin particles contain a biodegradable resin, and have a volume average particle diameter of 5 μm or more and 50 μm or less, and Relative Span Factor (R.S.F) of 1.2 or less.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to resin particles and a method for producing resin particles. [Background technology]

[0002] Resin particles, taking advantage of their large specific surface area and particle structure, are used to modify and improve various materials. Major applications include compounding agents for cosmetics such as foundations, antiperspirants, and scrubs; matting agents for paints; rheology modifiers; antiblocking agents; slipping agents; light diffusing agents; and various agents for medical diagnostic testing; as additives for molded articles such as automotive materials and building materials. Examples of resin particles include urethane, acrylic, silicone, and polyethylene.

[0003] Meanwhile, with the recent increase in interest in environmental issues, there is a demand to use non-petroleum-derived materials and biodegradable materials in all fields where resins are used in order to reduce the environmental impact, including in fields where resin particles are used, such as cosmetics and paints.

[0004] Known methods for producing biodegradable resin particles to date include a pulverization method, typified by freeze-pulverization (Patent Document 1), a solvent dissolution precipitation method in which the resin is dissolved in a solvent at high temperature and then cooled to precipitate, or dissolved in a solvent and then precipitated by adding a poor solvent (Patent Documents 2 and 3), and a method in which the resin is emulsified at high temperature using a solvent that does not dissolve the resin and a large amount of emulsifier (Patent Document 4). Summary of the Invention [Problem to be solved by the invention]

[0005] However, when used in external preparations such as cosmetics, the resin particles of Patent Document 1 have issues such as not being spherical and not achieving a fine particle size, and further improvement is required in terms of spreadability on the skin. Furthermore, the resin particles obtained in Patent Documents 2 to 4 are relatively spherical, but are insufficient in terms of adhesion to the skin and soft spreadability on the skin, and further improvement is required. Soft spreadability on the skin refers to the softness on the skin and the spreadability. This soft spreadability on the skin is thought to be related to the softness of the particles, the rolling properties of the particles due to their circularity, and the smooth feel of the powder due to the uniformity of the particle size.

[0006] An object of the present invention is to provide resin particles containing a biodegradable resin, which are suitable for use in cosmetics and have excellent adhesion to the skin and a soft feel on the skin when used. [Means for solving the problem]

[0007] The resin particles of the present invention as a means for solving the problem are resin particles containing a biodegradable resin, and have a volume average particle size of 5 μm or more and 50 μm or less, and a relative span factor (RSF) of 1.2 or less. is. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide resin particles containing a biodegradable resin, which are suitable for use in cosmetics and have excellent adhesion to the skin and a soft feel on the skin when used. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is a diagram showing an example of particle size distribution of particles produced by the method of this embodiment and particles produced by spray drying. [Figure 2] FIG. 2 is a schematic cross-sectional view showing an example of a liquid column resonance droplet ejection means. [Figure 3] FIG. 3 is a schematic diagram showing an example of a resin particle manufacturing apparatus. [Figure 4]FIG. 4 is a schematic cross-sectional view showing an example of a droplet discharge means used in a resin particle manufacturing apparatus. [Figure 5] FIG. 5 is a schematic cross-sectional view showing another example of the droplet discharge means used in the resin particle manufacturing apparatus. [Figure 6] FIG. 6 is a schematic cross-sectional view showing an example of a Rayleigh breakup droplet ejection means. DETAILED DESCRIPTION OF THE INVENTION

[0010] The present inventors have studied resin particles for use in cosmetics and have found the following. In conventional techniques, particle characteristics are determined using indicators such as volume average particle diameter and weight average particle diameter. The present inventors have discovered that, for resin particles containing a biodegradable resin, by controlling the volume average particle diameter to 5 μm or more and 50 μm or less and the relative span factor (RSF) to 1.2 or less, it is possible to provide resin particles for use in cosmetics that have excellent adhesion to the skin and a soft feel on the skin.

[0011] The resin particles of the present invention will be described in more detail below.

[0012] (resin particles) The resin particles of the present invention contain a biodegradable resin as a base material and, if necessary, further contain other components, such as a physiologically active substance and a dispersion stabilizer. The resin particles of the present invention have excellent adhesion to the skin and a soft feel when used on the skin, and therefore can be suitably used as resin particles for cosmetics. For example, a foundation can be prepared by mixing the resin particles of the present invention with a pigment, an oily base, an emulsifier, a preservative, a fragrance, etc.

[0013] <Particle size distribution> The resin particles of the present invention have a relative span factor (RSF) of 1.2 or less.

[0014] In this application, "Relative Span Factor (RSF)" is defined as (D90-D10) / D50, and is an index representing the narrowness of particle size distribution. D90 represents the cumulative 90% by number from the small particle side of the cumulative particle size distribution, D50 represents the cumulative 50% by number from the small particle side of the cumulative particle size distribution, and D10 represents the cumulative 10% by number from the small particle side of the cumulative particle size distribution. The smaller the (RSF) value, the narrower the particle size distribution. Examples of methods for measuring (RSF) include a method using a concentrated system analyzer ("FPAR-1000", manufactured by Otsuka Electronics Co., Ltd.) that uses dynamic light scattering, and a particle size distribution analyzer ("LA-960", manufactured by Horiba, Ltd.) that uses laser diffraction / scattering.

[0015] Other indices of the narrowness of particle size distribution include, for example, the ratio of volume average particle diameter (Dv) to number average particle diameter (Dn). The ratio of volume average particle diameter (Dv) to number average particle diameter (Dn) is the value obtained by dividing the volume average particle diameter (Dv) by the number average particle diameter (Dn), and the smaller the value, the narrower the particle size distribution. The ratio of volume average particle diameter (Dv) to number average particle diameter (Dn) of the resin particles of the present invention is preferably 1.00 or more and 1.50 or less, and more preferably 1.00 or more and 1.20 or less. Examples of methods for measuring the volume average particle diameter (Dv) and number average particle diameter (Dn) include a method using a laser diffraction / scattering particle size distribution analyzer (device name: Microtrac MT3000II, manufactured by Microtrac-Bell Co., Ltd.) or a laser diffraction / scattering particle size distribution analyzer (LA-960, manufactured by Horiba, Ltd.).

[0016] <Volume average particle size> The resin particles of the present invention have a volume average particle size (Dv) of 5 μm or more and 50 μm or less, and more preferably 10 μm or more and 30 μm or less from the viewpoint of the feel and soft spreadability on the skin.

[0017] <Average circularity> The average circularity (E) of the resin particles of the present invention is preferably greater than 0.980, and more preferably 0.985 or greater from the viewpoint of the feel and soft spreadability on the skin. The average circularity can be measured, for example, using a flow particle image analyzer (product name "FPIA (registered trademark)-3000S", manufactured by Sysmex Corporation). Specifically, the measurement method involves adding 0.2 g of the particle group to be measured to 20 ml of a 0.25% aqueous solution of sodium dodecylbenzenesulfonate, and irradiating the particles with ultrasonic waves for 5 minutes using an ultrasonic cleaner "MCD-10" manufactured by AS ONE Corporation as a disperser, thereby dispersing the particle group in the aqueous surfactant solution and preparing a dispersion for measurement. For the measurement, the above-mentioned flow particle image analyzer equipped with a standard objective lens (10x) is used, and the sheath liquid used in the flow particle image analyzer is Particle Sheath (trade name "PSE-900A", manufactured by Sysmex Corporation). The measurement dispersion prepared according to the above procedure is introduced into the flow particle image analyzer, and measurement is performed under the measurement conditions described below. Before starting the measurement, the flow particle image analyzer is automatically focused using a suspension of standard polymer particles (for example, "5200A" manufactured by ThermoFisherScientific (standard polystyrene particles diluted with ion-exchanged water)). The circularity is calculated by dividing the perimeter calculated from the diameter of a perfect circle having the same projected area as the image of the particle by the perimeter of the image of the particle. Measurement mode: HPF mode Particle size measurement range: 0.996 to 200 μm Measurement range of particle circularity: 0.5 to 1.0 Number of particles measured: 1000

[0018] <Biodegradable resin> The biodegradable resin is not particularly limited as long as it is a biodegradable resin, but is preferably at least one resin selected from the group consisting of polyester resins and polyamide resins. Examples of biodegradable polyester resins include polylactic acid; poly-ε-caprolactone; succinate polymers (polylactic acid-glycolic acid copolymers) such as polyethylene succinate, polybutylene succinate, and polybutylene succinate adipate; polybutylene adipate terephthalate; polyhydroxyalkanoates such as polyhydroxypropionate, polyhydroxybutyrate, and polyhydroxyvalerate; and polyglycolic acid. Examples of biodegradable polyamide resins include nylon 4. These resins may be used alone or in combination. The weight average molecular weight of the biodegradable resin is preferably 500,000 or less, and more preferably 50,000 or less.

[0019] <<Polylactic acid>> The weight average molecular weight Mw of polylactic acid is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 5,000 or more and 100,000 or less, more preferably 10,000 or more and 70,000 or less, even more preferably 10,000 or more and 50,000 or less, and particularly preferably 40,000 or more and 50,000 or less.

[0020] <<Polyglycolic acid>> The polyglycolic acid is not particularly limited and can be appropriately selected depending on the purpose. Examples include lactic acid-glycolic acid copolymer, which is a copolymer having structural units derived from lactic acid and structural units derived from glycolic acid; glycolic acid-caprolactone copolymer, which is a copolymer having structural units derived from glycolic acid and structural units derived from caprolactone; and glycolic acid-trimethylene carbonate copolymer, which is a copolymer having structural units derived from glycolic acid and structural units derived from trimethylene carbonate. These may be used alone or in combination. Among these, lactic acid-glycolic acid copolymer is preferred because of its high biocompatibility, ability to slowly release the physiologically active substance contained therein, and ability to preserve the physiologically active substance contained therein for a long period of time. Examples of lactic acid / glycolic acid copolymers that can be used include PURASORB PDLG5010, PURASORB PDLG7510, PURASORB PDLG7507, PURASORB PDLG5002A, PURASORB PDLG5002, and PURASORB PDLG7502A (manufactured by Corbion), and RG502, RG502H, RG503, RG503H, RG504, and RG504H (manufactured by Sigma-Aldrich). The weight average molecular weight of the lactic acid-glycolic acid copolymer is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 2,000 to 250,000, more preferably 2,000 to 100,000, and particularly preferably 40,000 to 50,000. The molar ratio (L:G) of the structural units (L) derived from lactic acid to the structural units (G) derived from glycolic acid in the lactic acid-glycolic acid copolymer is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 1:99 to 99:1, more preferably 25:75 to 99:1, even more preferably 30:70 to 90:10, and particularly preferably 50:50 to 85:15.

[0021] <<Polyhydroxyalkanoate>> Among polyhydroxyalkanoates, the polyhydroxyalkanoates represented by the general formula (1) [-CH(R)-CH2CO-O-] (wherein R is -C n H 2n+1 and n is an integer of 1 to 15). More specifically, a homopolymer of at least one monomer selected from the group consisting of 3-hydroxypropionate, 3-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxyhexanoate, 3-hydroxyheptanoate, 3-hydroxyoctanoate, 3-hydroxynonanoate, 3-hydroxydecanoate, 3-hydroxytetradecanoate, 3-hydroxyhexadecanoate, and 3-hydroxyoctadecanoate, and a copolymer thereof can be used. Specific examples of the homopolymer or copolymer of 3-hydroxyalkanoate include the above-mentioned 3-hydroxyalkanoate homopolymer, a copolymer of two or more 3-hydroxyalkanoates with different n's, and a mixture of two or more selected from the group consisting of the above-mentioned homopolymers and copolymers. Among these, homopolymers, copolymers and mixtures composed of at least one repeating unit selected from the group consisting of 3-hydroxybutyrate repeating units where n=1, 3-hydroxyvalerate repeating units where n=2, 3-hydroxyhexanoate repeating units where n=3, 3-hydroxyoctanoate repeating units where n=5 and 3-hydroxyoctadecanoate repeating units where n=15 are preferred, and copolymers composed of 3-hydroxybutyrate repeating units and at least one repeating unit selected from the group consisting of 3-hydroxyvalerate repeating units, 3-hydroxyhexanoate repeating units and 3-hydroxyoctanoate repeating units are more preferred. When a copolymer of 3-hydroxybutyrate and 3-hydroxyhexanoate is used, the ratio of 3-hydroxybutyrate to 3-hydroxyhexanoate is not particularly limited and can be selected appropriately depending on the purpose. However, as the ratio of 3-hydroxybutyrate increases, the viscosity of the particle composition liquid increases, making it difficult to eject droplets in the droplet ejection step. Therefore, the ratio of 3-hydroxybutyrate to 3-hydroxyhexanoate is preferably in the range of 94:6 to 80:20, and more preferably in the range of 90:10 to 80:20. The weight-average molecular weight Mw of the polyhydroxyalkanoate is not particularly limited and can be appropriately selected depending on the purpose. However, as the molecular weight increases, the viscosity of the particle composition liquid increases, making it difficult to eject droplets in the droplet ejection step. Therefore, the weight-average molecular weight Mw is preferably 2,000 to 1,000,000, and more preferably 2,000 to 600,000.

[0022] <Other ingredients> The resin particles of the present invention can be used in cosmetics and the like by combining them with other components such as physiologically active substances and dispersion stabilizers, as needed. Furthermore, the resin particles may be made into functional particles depending on various applications. Functional particles are not particularly limited and can be appropriately selected depending on the purpose. Examples of functional particles include immediate-release particles, sustained-release particles, pH-dependent release particles, pH-independent release particles, enteric-coated particles, controlled-release coated particles, and nanocrystal-containing particles.

[0023] <<Physiologically active substances>> The physiologically active substance is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include alcohols, fatty alcohols, and polyols, aldehydes, alkanolamines, alkoxylated alcohols (e.g., polyethylene glycol derivatives of alcohols, fatty alcohols, etc.), alkoxylated amides, alkoxylated amines, alkoxylated carboxylic acids, amides including salts (e.g., ceramides, etc.), amines, amino acids including salts and alkyl-substituted derivatives, esters, alkyl-substituted and acyl derivatives, polyacrylic acids, acrylamide copolymers, adipic acid copolymers, aminosilicones, biological polymers and derivatives thereof, butylene copolymers, carbohydrates (e.g., polysaccharides, chitosan, derivatives thereof, etc.), carboxylic acids, carbomers, esters, ethers, and polymer ethers. Examples of such surfactants include esters (e.g., polyethylene glycol (PEG) derivatives, polypropylene glycol (PPG) derivatives, etc.), glyceryl esters and their derivatives, halogen compounds, heterocyclic compounds containing salts, hydrophilic colloids and derivatives containing salts and rubbers (e.g., cellulose derivatives, gelatin, xanthan gum, natural rubbers, etc.), imidazolines, inorganic substances (clay, TiO, ZnO, etc.), ketones (e.g., camphor, etc.), isethionates, lanolin and its derivatives, organic salts, phenols containing salts (e.g., parabens, etc.), phosphorus compounds (e.g., phosphoric acid derivatives, etc.), polyacrylates and acrylate copolymers, protein and enzyme derivatives (e.g., collagen, etc.), synthetic polymers containing salts, siloxanes and silanes, sorbitan derivatives, sterols, sulfonic acids and their derivatives, and waxes. These may be used alone or in combination of two or more.

[0024] <<Dispersion stabilizer>> The dispersion stabilizer is not particularly limited, but alkaline earth metal salts, such as poorly water-soluble inorganic compounds such as calcium carbonate and calcium phosphate, can be used. Among these, calcium carbonate surface-treated with a silane coupling agent is preferred because it is highly compatible with biodegradable resins and has excellent dispersion stability. The amount of alkaline earth metal component contained in the resin particles is preferably less than 10 ppm relative to the mass of the entire resin particles, from the viewpoint of preventing moisture in the air from being adsorbed onto the dispersion stabilizer and causing aggregation of the resin particles, and is preferably 0.05 ppm or more to obtain the effect of dispersion stabilization.

[0025] The amount of alkaline earth metal components contained in resin particles can be measured, for example, by the following method: 1.0 g of resin particles to be measured is precisely weighed into a crucible and heated in an electric furnace at 450°C for 3 hours to incinerate the resin particles. The incinerated resin particles are dissolved in 2 ml of concentrated hydrochloric acid, and the resulting solution is adjusted to 50 ml with ultrapure water to prepare a measurement sample. The amount of alkaline earth metal components can be measured using a multi-type ICP optical emission spectrometer (Shimadzu Corporation, "ICPE-9000").

[0026] (Method of producing resin particles) The method for producing resin particles of the present invention includes a droplet ejection step of ejecting a particle composition liquid containing a biodegradable resin and a solvent into a gas as droplets, and a granulation step of removing the solvent from the droplets to granulate particles, and may include other steps as necessary.

[0027] Several dry granulation methods for granulating particles in air have been known. Examples include an air pulverization method in which particulate material is melt-kneaded to uniformly disperse the material, cooled, and then pulverized using a pulverizer to obtain small pulverized particles, and a liquid containing particulate material is freeze-dried and then pulverized using a pulverizer to obtain small pulverized particles. Another example is the spray drying method, in which a liquid containing particulate material is sprayed into the air and dried to obtain small atomized particles. Examples of atomization methods include the pressurized nozzle method, in which the liquid is pressurized and sprayed from a nozzle, and the disk method, in which the liquid is sent to a rapidly rotating disk and scattered by centrifugal force.

[0028] In the air milling method, the equipment used for milling is simple, but it is difficult to produce particles with a narrow particle size distribution.

[0029] While the spray drying method can produce particles with a high proportion of physiologically active substances retained in the particles (bioactive substance retention rate) after the particle production process, it is generally difficult to produce particles with small particle sizes. When the atomization method is a disk type, it may be possible to produce particles with small particle sizes, but large-scale equipment is required.

[0030] The method for producing resin particles of this embodiment described below does not correspond to the above-mentioned air grinding method and spray drying method, and is capable of producing particles with a high proportion of physiologically active substances retained in the particles (physiologically active substance retention rate) after the particle production process, and is also capable of producing particles with a small particle size.

[0031] -Droplet discharge process- The droplet ejection step is a step of ejecting a particle composition liquid containing a biodegradable resin and a solvent into a gas as droplets.

[0032] The method for ejecting droplets is not particularly limited, but examples thereof include the following methods. (i) A method using a discharge means that discharges pressurized liquid as droplets from holes provided on a flat nozzle formation surface such as an inkjet nozzle. (ii) A method using a discharge means that discharges pressurized liquid as droplets from holes in an irregular shape such as an SPG membrane. (iii) A method using a discharge means for discharging the vibrated liquid from a hole as droplets.

[0033] Examples of the vibration-based discharge means (iii) that do not alter the physiological activity of the physiologically active substance due to the vibration include discharge means that are unlikely to apply external stress to the particle composition liquid itself, such as a discharge means that utilizes a membrane vibration method, a discharge means that utilizes a Rayleigh fragmentation method, a discharge means that utilizes a liquid vibration method, and a discharge means that utilizes a liquid column resonance method. These discharge means may further include a means for applying pressure to the liquid to discharge it. Among these means, a discharge means that utilizes a liquid column resonance method and further includes a means for applying pressure to the liquid to discharge it is preferred.

[0034] An example of an ejection means utilizing the liquid column resonance method is an ejection means that uses a method in which a standing wave is formed by liquid column resonance by applying vibration to the liquid contained in a liquid column resonance liquid chamber, and the liquid is ejected from an ejection hole formed in the amplitude direction of the standing wave in the region that becomes the antinode of the standing wave. Note that an example of a discharge means utilizing the membrane vibration method is the discharge means described in Japanese Patent Application Laid-Open No. 2008-292976 (WO2008 / 114655). An example of a discharge means utilizing the Rayleigh fragmentation method is the discharge means described in Japanese Patent Application Laid-Open No. 2008-065009 (US2008 / 0063971). An example of a discharge means using the liquid vibration method is the discharge means described in Japanese Patent Application Laid-Open No. 2010-102195 (US2010 / 0104970).

[0035] As an example of the droplet ejection process, a method of ejecting a particle composition liquid containing a biodegradable resin and a solvent as droplets by vibration will be described again. The method of discharging by vibration is not particularly limited, but examples thereof include the following methods, each of which will be described below. (a) A method using a volume change means that changes the volume of the liquid storage portion by using vibrations (b) A method using a constriction generating means in which the liquid is discharged from a plurality of discharge holes provided in the liquid storage section while applying vibration to the liquid storage section, and the liquid changes from a columnar shape to a constricted state and then to droplets. (c) A method using a nozzle vibration means that vibrates a thin film on which a nozzle is formed.

[0036] There are no particular restrictions on the volume change means as long as it can change the volume of the liquid storage section, and it can be selected appropriately depending on the purpose.For example, a piezoelectric element (sometimes called a "piezo element") that expands and contracts when voltage is applied can be used. An example of a constriction generating means is a means using the technology described in Japanese Patent Application Laid-Open No. 2008-065009 (US2008 / 0063971). Japanese Patent Application Laid-Open No. 2008-065009 (US2008 / 0063971) describes a means for discharging liquid from a plurality of nozzle holes provided in a liquid storage portion while applying vibrations to the liquid storage portion using a vibration means that uses a piezoelectric element in contact with a part of the liquid storage portion, causing the liquid to change from a columnar shape to a constricted state and then to droplets. An example of a nozzle vibration means is a means using the technology described in Japanese Patent Application Laid-Open No. 2008-292976 (WO2008 / 114655). Japanese Patent Application Laid-Open No. 2008-292976 (WO2008 / 114655) describes a means for ejecting liquid from a plurality of nozzle holes and turning it into droplets using a thin film provided in a liquid storage section and having a plurality of nozzles formed therein, and a piezoelectric element disposed around the deformable area of ​​the thin film and vibrating the thin film.

[0037] A piezoelectric element is generally used as a means for generating vibrations. The piezoelectric element is not particularly limited, and the shape, size, and material can be appropriately selected. For example, a piezoelectric element used in a conventional inkjet ejection method can be suitably used. There are no particular limitations on the shape and size of the piezoelectric element, and they can be selected appropriately according to the shape of the discharge hole, etc. The material of the piezoelectric element is not particularly limited and can be selected appropriately depending on the purpose. Examples include piezoelectric ceramics such as lead zirconate titanate (PZT), piezoelectric polymers such as polyvinylidene fluoride (PVDF), and single crystals such as quartz, LiNbO3, LiTaO3, and KNbO3.

[0038] The ejection holes are not particularly limited and can be appropriately selected depending on the purpose. For example, openings provided in a nozzle plate or the like can be mentioned.

[0039] The cross-sectional shape and size of the discharge hole can be selected appropriately. The cross-sectional shape of the discharge hole is not particularly limited and can be selected appropriately depending on the purpose, and examples include: (1) a tapered shape in which the opening diameter decreases from the inside (liquid storage section side) to the outside (side from which the liquid is discharged), (2) a shape in which the opening diameter narrows while maintaining a rounded shape from the inside (liquid storage section side) to the outside (side from which the liquid is discharged), (3) a shape in which the opening diameter narrows at a certain nozzle angle from the inside (liquid storage section side) to the outside (side from which the liquid is discharged), (4) a combination of shapes (1) and (2), etc. Among these, shape (3) is preferred because it maximizes the pressure applied to the liquid at the discharge hole. The nozzle angle in the shape of (3) is not particularly limited and can be appropriately selected depending on the purpose, but is preferably between 60° and 90°. When the nozzle angle is between 60° and 90°, droplet ejection can be stabilized.

[0040] The size of the ejection hole is not particularly limited and can be appropriately selected depending on the purpose, for example, the diameter is preferably less than 1,000 μm, more preferably 1.0 μm or more and less than 1,000 μm, even more preferably 1.0 μm or more and 500 μm or less, and particularly preferably 1.0 μm or more and 50 μm or less. If the shape of the ejection hole is not a perfect circle, the diameter of a perfect circle having the same area as the area of ​​the ejection hole is used.

[0041] <Particle composition liquid> The liquid (particle composition liquid) ejected in the droplet ejection process contains a biodegradable resin and a solvent, but since the biodegradable resin contained in the particle composition liquid can be made from various materials similar to the biodegradable resin contained in the resin particles of the present invention, we will omit the explanation and only explain the solvent. The content of the biodegradable resin in the particle composition liquid is not particularly limited and can be appropriately selected depending on the purpose.

[0042] It is preferable that the particle composition liquid and the solvent are substantially free of surfactants. By being substantially free of surfactants, safety can be improved when the produced particles are contained in pharmaceutical compositions, functional foods, functional cosmetics, etc. Here, "substantially free of surfactants" refers to, for example, when the content of surfactants in the particle composition liquid and the solvent is below the detection limit that cannot be detected by liquid chromatography, when no surfactant is contained in the particle composition liquid and the solvent, etc.

[0043] <<Solvent>> Examples of solvents include water, aliphatic halogenated hydrocarbons (e.g., dichloromethane, dichloroethane, chloroform, etc.), alcohols (e.g., methanol, ethanol, propanol, 3-methoxy-3-methyl-1-butanol, 2,2,2-trifluoroethanol, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), ethers (e.g., diethyl ether, dibutyl ether, 1,4-dioxane, etc.), aliphatic hydrocarbons (e.g., n-hexane, cyclohexane, n-heptane, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, etc.), organic acids (e.g., acetic acid, propionic acid, etc.), esters (e.g., ethyl acetate, 3-methoxy-3-methyl-1-butyl acetate, etc.), amides (e.g., dimethylformamide, dimethylacetamide, etc.), and mixed solvents thereof. These may be used alone or in combination of two or more. Among these, aliphatic halogenated hydrocarbons, alcohols, or mixed solvents thereof are preferred in terms of solubility, and dichloromethane, 1,4-dioxane, dimethylformamide, acetonitrile, or mixed solvents thereof are more preferred.

[0044] The content of the solvent is preferably 70% by mass or more and 99.5% by mass or less, and more preferably 90% by mass or more and 99% by mass or less, based on the mass of the particle composition liquid. When the content is 70% by mass or more and 99.5% by mass or less, production stability is improved in terms of the solubility of the particle material and the liquid viscosity.

[0045] The viscosity of the particle composition liquid is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 0.5 mPa·s or more and 15.0 mPa·s or less, and more preferably 0.5 mPa·s or more and 10.0 mPa·s or less. The viscosity is measured, for example, using a viscoelasticity measuring device (device name: MCR rheometer, manufactured by Anton Paar) at 25°C and a shear rate of 10 s -1 It is preferable that the viscosity of the liquid is 0.5 mPa·s or more and 15.0 mPa·s or less, because this allows suitable ejection in the above-mentioned means for ejecting droplets.

[0046] The surface tension of the particle composition liquid is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 10 mN / m to 60 mN / m, and more preferably 20 mN / m to 50 mN / m. The surface tension can be measured, for example, using a handheld surface tensiometer (PocketDyne, manufactured by KRUSS) by the maximum bubble pressure method at 25°C with a lifetime of 1,000 ms. A surface tension of 0.5 mPa·s to 15.0 mPa·s is preferred because it allows for suitable ejection in the droplet ejection means.

[0047] -Granulation process- The granulation step is a step in which the solvent contained in the droplets is evaporated to remove the solvent from the droplets, thereby granulating particles. The granulation step is preferably carried out in a gas, specifically while the droplets discharged into the gas in the droplet discharge step are flying in the gas.

[0048] Unlike conventional spray drying methods, the particles produced by this method are produced by ejecting droplets of approximately uniform size while controlling the droplets so that they do not coalesce, and then granulating the droplets by evaporating the solvent.This makes it possible to produce large quantities of particles of uniform size, and therefore to narrow the particle size distribution. Fig. 1 is a diagram showing an example of particle size distribution of particles produced by the method of this embodiment and particles produced by spray drying. As shown in Fig. 1, unlike particles produced by spray drying, the particles produced by the method of this embodiment show only one narrow peak in the particle size distribution, and no peak indicating coarse particles appears. Furthermore, the particle size can be adjusted by appropriately adjusting the size of the ejection holes of the ejection means that forms the droplets.

[0049] In the granulation step, droplets may be ejected into a transport airflow to vaporize the solvent from the droplets, thereby forming particles. The method for vaporizing the solvent from the droplets using a transport airflow is not particularly limited and can be appropriately selected depending on the purpose. For example, a method in which the transport direction of the transport airflow is approximately perpendicular to the ejection direction of the droplets is preferred. It is also preferable to appropriately adjust the temperature, vapor pressure, type of gas, etc. of the transport airflow. A heating means may be provided to adjust the temperature of the transport airflow. However, as described above, in the granulation process, ejection is performed while suppressing coalescence of droplets. Therefore, the degree of heating by the heating means can be suppressed, specifically, heating can be performed to an extent that does not change the physiological activity of the physiologically active substance.

[0050] Furthermore, as long as the collected particles remain in a solid state, the solvent does not need to be completely vaporized, and a drying process may be added as a separate process after collection. The spray liquid may be heated to a temperature above the melting point of the biodegradable resin, and after spraying, the biodegradable resin in the droplets may be solidified by the cooling effect of the solvent vaporization, thereby forming particles. Alternatively, a method of vaporizing the solvent from the droplets by applying a temperature change or a chemical change may be used.

[0051] -Other processes- The other steps are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include a particle collection step. The particle collection step is a step of collecting the produced particles, and can be suitably carried out by a particle collection means. The particle collection means is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include cyclone collection and a back filter.

[0052] When producing particles containing at least two types of base materials, one of which is concentrated on the surface side, particles of this type can be formed in the granulation process by appropriately selecting the type of base material contained in the particle composition liquid. In the granulation step, to form particles in which one of the at least two types of substrates is concentrated on the surface side, the contact angles of the at least two types of substrates are made different from each other, which increases the interaction between the substrates when the solvent is evaporated from the droplets in the granulation step. At this time, since the contact angles of the at least two types of substrates are different from each other, the substrates are likely to undergo phase separation. As a result, one of the at least two types of substrates is biased toward the surface side, and then, as the solvent evaporates, solidified particles are formed in that state. This method makes it possible to form particles in which one of the at least two types of substrates is biased toward the surface side in just one step.

[0053] Other steps besides those mentioned above include, for example, a step of filtering or sieving the particles after granulation to obtain particles of uniform size, and an additional drying step to remove the solvent in the particles.

[0054] The amount of solvent contained in the particles is preferably less than 1% as measured by gas chromatography. If it is 1% or more, the particles tend to stick together, causing aggregation, which worsens the particle size distribution and increases the span factor. Furthermore, the amount of residual solvent is preferably 1 ppm or more. If it is less than 1 ppm, there is insufficient solvent in the spray liquid, and the viscosity of the spray liquid is high, making it difficult to form particles.

[0055] The amount of residual solvent in particles is measured by adding 2 parts by weight of 2-propanol to 1 part by weight of particles to be measured, dispersing the particles ultrasonically for 30 minutes, storing the particles in a refrigerator (5°C) for at least one day to extract the solvent in the particles, and analyzing the supernatant by gas chromatography (GC-14A, SHIMADZU) to quantify the amount of solvent in the particles.

[0056] <Resin particle manufacturing equipment> The resin particle manufacturing apparatus includes a droplet ejection means for ejecting a particle composition liquid containing a biodegradable resin and a solvent into a gas as droplets, and a granulation means for removing the solvent from the droplets to form particles, and may also include other means as necessary.

[0057] -Droplet discharge means- The droplet ejection means is a means for ejecting a particle composition liquid containing a biodegradable resin and a solvent into a gas to form droplets. In a preferred embodiment, the droplet ejection means ejects the particle composition liquid by vibration to form droplets. The droplet ejection means is connected to a liquid storage container, which will be described later. There are no particular limitations on the means for connecting the droplet ejection means to the liquid storage container, and the means can be appropriately selected depending on the purpose, as long as it can supply liquid from the liquid storage container to the droplet ejection means. For example, a pipe (a tube, etc.) can be used. The droplet ejection means preferably has a vibration-imparting member that imparts vibration to the liquid to eject droplets. The vibration is not particularly limited and can be selected appropriately depending on the purpose. For example, the frequency is preferably 1 kHz or higher, more preferably 150 kHz or higher, and even more preferably 300 kHz to 500 kHz. Vibration of 1 kHz or higher can reproducibly convert the liquid column sprayed from the ejection hole into droplets, while vibration of 150 kHz or higher can improve production efficiency. An example of a droplet ejection means having a vibration-applying member is an inkjet nozzle, etc. The ejection mechanism of the inkjet nozzle may be, for example, a liquid column resonance method, a membrane vibration method, a liquid vibration method, a Rayleigh fragmentation method, etc.

[0058] Next, a liquid column resonance droplet ejection means will be specifically described as an example of the droplet ejection means. It should be understood by those skilled in the art that the droplet ejection means is not limited to the liquid column resonance droplet ejection means, but other droplet ejection means (for example, an ejection means using a membrane vibration method, an ejection means using a Rayleigh breakup method, an ejection means using a liquid vibration method, etc.) may also be used.

[0059] 2 is a schematic cross-sectional view showing an example of a liquid column resonance droplet ejection means. The liquid column resonance droplet ejection means 11 has a common liquid supply channel 17 and a liquid column resonance liquid chamber 18. The liquid column resonance liquid chamber 18 is connected to the common liquid supply channel 17, which is provided on one of the wall surfaces at both ends in the longitudinal direction. The liquid column resonance liquid chamber 18 also has an ejection hole 19, which ejects droplets 21, on one of the wall surfaces connecting to the end wall surfaces, and a vibration generating means 20, which is provided on the wall surface facing the ejection hole 19 and generates high-frequency vibrations to form liquid column resonance standing waves. A high-frequency power source is connected to the vibration generating means 20. An airflow passage may also be provided to supply an airflow that transports the droplets 21 ejected from the liquid column resonance droplet ejection means 11.

[0060] A particle composition liquid 14 containing a biodegradable resin and a solvent is passed through a liquid supply pipe by a liquid circulation pump, flows into a common liquid supply channel 17 of the liquid column resonance droplet ejection means 11, and is supplied to a liquid column resonance liquid chamber 18.

[0061] Then, in the liquid column resonance liquid chamber 18 filled with the particle composition liquid 14, a pressure distribution is formed by the liquid column resonance standing wave generated by the vibration generating means 20. Then, droplets 21 are ejected from ejection holes 19 located in the antinode region of the standing wave, where the amplitude of the liquid column resonance standing wave is large and the pressure fluctuation is large. The region that becomes the antinode of the standing wave due to this liquid column resonance is a region other than the node of the standing wave, and is preferably a region where the pressure fluctuation of the standing wave has an amplitude large enough to eject liquid, and more preferably a region of ±1 / 4 wavelength from the position where the amplitude of the pressure standing wave is maximum (antinode as a velocity standing wave) to the position where it is minimum. In the region where the antinode of the standing wave is formed, even if multiple discharge holes are opened, substantially uniform droplets can be formed from each of them. Furthermore, droplets can be discharged efficiently and the discharge holes are less likely to become clogged. The particle composition liquid 14 that has passed through the common liquid supply channel 17 is circulated by a liquid return pipe. When the amount of particle composition liquid 14 in the liquid column resonance liquid chamber 18 decreases due to the discharge of droplets 21, a suction force is generated by the action of the liquid column resonance standing wave in the liquid column resonance liquid chamber 18, and the flow rate of the particle composition liquid 14 supplied from the common liquid supply channel 17 increases. Then, the particle composition liquid 14 is replenished in the liquid column resonance liquid chamber 18. When the particle composition liquid 14 is replenished in the liquid column resonance liquid chamber 18, the flow rate of the particle composition liquid 14 passing through the common liquid supply channel 17 returns to normal.

[0062] The liquid column resonance liquid chamber 18 in the liquid column resonance droplet ejection means 11 is formed by joining together frames made of materials such as metal, ceramics, and silicone that have high rigidity so as not to affect the resonant frequency of the liquid at the driving frequency. As shown in FIG. 2, the length L between the wall surfaces at both ends of the liquid column resonance liquid chamber 18 in the longitudinal direction is determined based on the liquid column resonance principle. Furthermore, it is preferable to arrange a plurality of liquid column resonance liquid chambers 18 for one droplet formation unit in order to dramatically improve productivity. The number of liquid column resonance liquid chambers 18 is not particularly limited, but is preferably 1 to 2,000. Furthermore, a flow path for supplying liquid is connected to each liquid column resonance liquid chamber from a common liquid supply channel 17, and the common liquid supply channel 17 is connected to a plurality of liquid column resonance liquid chambers . Furthermore, there are no particular limitations on the vibration generating means 20 in the liquid column resonance droplet ejection means 11 as long as it can be driven at a predetermined frequency, but a configuration in which a piezoelectric body is bonded to an elastic plate 9 is preferred. From the viewpoint of productivity, the frequency is more preferably 150 kHz or more, and even more preferably 300 kHz or more and 500 kHz or less. The elastic plate constitutes a part of the wall of the liquid column resonance liquid chamber so that the piezoelectric body does not come into contact with the liquid. Examples of piezoelectric materials include piezoelectric ceramics such as lead zirconate titanate (PZT), which are often used in layers due to their generally small displacement. Other examples include piezoelectric polymers such as polyvinylidene fluoride (PVDF), and single crystals such as quartz, LiNbO3, LiTaO3, and KNbO3. Furthermore, it is preferable that the vibration generating means 20 is arranged so that it can be controlled individually for each liquid column resonance liquid chamber. Furthermore, it is preferable to configure the block-shaped vibration member made of one of the above materials so that it is partially cut to fit the arrangement of the liquid column resonance liquid chambers, and each liquid column resonance liquid chamber can be individually controlled via an elastic plate. Furthermore, it is preferable to adopt a configuration in which the discharge holes 19 are provided in the width direction within the liquid column resonance liquid chamber 18, since this allows for the provision of a large number of openings for the discharge holes 19 and increases production efficiency. Furthermore, since the liquid column resonance frequency varies depending on the opening arrangement of the ejection holes 19, it is desirable to determine the liquid column resonance frequency appropriately by checking the ejection of droplets.

[0063] <<Particle composition liquid container>> The particle composition liquid container is a container that contains a particle composition liquid containing a biodegradable resin and a solvent. The particle composition liquid storage container may be flexible or inflexible. The material of the particle composition liquid storage container is not particularly limited and can be appropriately selected depending on the purpose, and may be made of, for example, resin or metal. The structure of the particle composition liquid storage container is not particularly limited and can be appropriately selected depending on the purpose, and may be, for example, a sealed structure or a non-sealed structure.

[0064] -Granulation means- The granulation means is a means for granulating particles by vaporizing the solvent from the droplets and removing the solvent contained in the droplets. The granulation means may be, for example, a member that forms a space for evaporating the solvent from the droplets. The granulating means preferably has a conveying airflow forming means for forming a conveying airflow.

[0065] Next, an example of an embodiment will be described with reference to FIGS. Fig. 3 is a schematic diagram showing an example of a resin particle manufacturing apparatus, Fig. 4 is a schematic cross-sectional view showing an example of a droplet discharge means used in the resin particle manufacturing apparatus, and Fig. 5 is a schematic cross-sectional view showing another example of a droplet discharge means used in the resin particle manufacturing apparatus. 3 includes a droplet discharge means 302, a drying and collecting unit 360, a conveying airflow outlet 365, and a particle reservoir 363. The droplet discharge means 302 is connected to a particle composition liquid storage container 313 that stores a particle composition liquid 314, and a liquid circulation pump 315 that supplies the particle composition liquid 314 stored in the particle composition liquid storage container 313 to the droplet discharge means 302 through a liquid supply pipe 316 and further to return the particle composition liquid 314 to the particle composition liquid storage container 313 through a liquid return pipe 322. This allows the particle composition liquid 314 to be supplied to the droplet discharge means 302 at any time. A pressure gauge P1 is provided on the liquid supply pipe 316, and a pressure gauge P2 is provided on the drying and collecting unit. The liquid supply pressure to the droplet discharge means 302 and the pressure within the drying and collecting unit are controlled by the pressure gauges P1 and P2. At this time, if the pressure measurement value of P1 is greater than the pressure measurement value of P2, there is a risk that the particle composition liquid 314 will seep out from the discharge hole, and if the pressure measurement value of P1 is smaller than the pressure measurement value of P2, there is a risk that gas will enter the droplet discharge means 302 and discharge will stop, so it is preferable that the pressure measurement values ​​of P1 and P2 are approximately the same. In the chamber 361, a downward air current (carrying air current) 301 is formed from the carrying air current inlet 364. The droplets 321 discharged from the droplet discharge means 302 are carried downward not only by gravity but also by the carrying air current 301, pass through the carrying air current outlet 365, are collected by the particle collecting means 362, and are stored in the particle storage section 363. In the droplet discharge process, if discharged droplets come into contact with each other before drying, they may coalesce. To obtain particles with a narrow particle size distribution, it is preferable to maintain a distance between the discharged droplets. However, although discharged droplets have a certain initial velocity, they eventually lose speed due to air resistance. If subsequently discharged droplets catch up with the stalled droplets and the droplets are not sufficiently dried, the droplets may coalesce. To prevent coalescence, it is preferable to suppress the decrease in droplet speed and transport the droplets while drying them using the transport airflow 301 to prevent droplets from coming into contact with each other. Therefore, it is preferable to arrange the transport airflow 301 in the same direction as the droplet discharge direction near the droplet discharge means 302. Even if droplets come into contact with each other, they will not coalesce if they are sufficiently dry by the time of contact. In such cases, the transport airflow 301 may not be used.

[0066] Fig. 4 is an enlarged view of the droplet discharge means of the resin particle manufacturing apparatus in Fig. 3. As shown in Fig. 4, droplet discharge means 302 has volume change means 320, elastic plate 309, and particle composition liquid storage section 319. When a voltage is applied to volume change means 320, droplet discharge means 302 deforms to reduce the volume of particle composition liquid storage section 319, and discharges the particle composition liquid stored in particle composition liquid storage section 319 from the discharge hole as droplets 321.

[0067] FIG. 5 is a diagram showing another embodiment of the droplet discharge means of the resin particle manufacturing apparatus. As shown in FIG. 5, in the airflow passage 312, the transport airflow 301 may be substantially perpendicular to the discharge direction. The transport airflow 301 may be angled, preferably at an angle that causes the droplets to move away from the droplet discharge means 302. As shown in FIG. 5, when droplets 321 are discharged by changing the volume of the particle composition liquid storage section 319 via the elastic plate 309 using the volume change means 320 and a coalescence prevention transport airflow 301 is applied substantially perpendicular to the discharged droplets 321, it is preferable to position the discharge holes so that the trajectories of the droplets do not overlap when they are transported from the discharge holes by the coalescence prevention transport airflow 301. After preventing coalescence by the transport airflow 301, the particles may be transported to the particle collecting means by another airflow. The speed of the transport air current is preferably equal to or greater than the droplet ejection speed. If the speed of the transport air current is greater than the droplet ejection speed, the adhesion of droplets to each other can be suppressed. Furthermore, a chemical substance that promotes drying of the droplets may be mixed into the transport airflow. The state of the transport airflow is not limited, and may be a laminar flow, a swirling flow, or a turbulent flow. The type of gas that constitutes the transport airflow is not particularly limited, and may be appropriately selected depending on the purpose. Air or a non-flammable gas such as nitrogen may be used. The temperature of the transport airflow can be adjusted as appropriate, but should be such that the physiological activity of the physiologically active substance contained in the droplets does not change depending on the temperature of the airflow.

[0068] If the amount of residual solvent contained in the particles obtained by the particle collecting means 362 shown in Fig. 3 is large, it is preferable to perform secondary drying as necessary to reduce the amount of residual solvent. As the secondary drying, a commonly known drying means such as fluidized bed drying or vacuum drying can be used.

[0069] As an example of droplet ejection means, an ejection means using the Rayleigh breakup method will be described with reference to FIG. Fig. 6 is a schematic cross-sectional view showing an example of a Rayleigh breakup droplet ejection means. A preferable droplet ejection means has at least a reservoir 401 for storing a particle composition liquid, a vibration means 402, and a plurality of through-holes 403, as shown in Fig. 6.

[0070] Since the reservoir 401 must at least hold the particle composition liquid under pressure, it is preferably made of a metal such as SUS or aluminum and has a pressure resistance of approximately 10 MPa, but is not limited thereto. Furthermore, as shown in FIG. 6 , a desirable structure includes a through-hole holding mechanism 405 connected to the reservoir 401 by a supply pipe 404 that supplies the liquid to the reservoir 401 and that holds a plate having a through-hole 403 for ejecting droplets 409. A vibration means 402 that vibrates the entire reservoir 401 is in contact with the reservoir 401. The vibration means 402 is preferably connected to a vibration generator 406 by a conductive wire 407 and is preferably controlled. Adjusting the pressure within the reservoir 401 and providing an open valve 408 for removing internal bubbles are desirable for stable formation of a liquid column.

[0071] It is preferable that one vibration means 402 is used to vibrate the entire storage section 401. There are no particular limitations on the vibration means 402 that applies vibration to storage section 401 as long as it can reliably apply vibration at a constant frequency, and any suitable means can be selected and used, but from the above-mentioned viewpoint, it is preferable that, for example, through-hole 403 is vibrated at a constant frequency by expansion and contraction of a piezoelectric body.

[0072] The piezoelectric body has a function of converting electrical energy into mechanical energy. Specifically, when a voltage is applied, the piezoelectric body expands and contracts, and this expansion and contraction causes the through-hole 403 to vibrate. Examples of the piezoelectric material include piezoelectric ceramics such as lead zirconate titanate (PZT), which are often used in layers due to their generally small displacement. Other examples include piezoelectric polymers such as polyvinylidene fluoride (PVDF), and single crystals such as quartz, LiNbO3, LiTaO3, and KNbO3. The constant frequency is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 10 kHz to 10 MHz, and more preferably 50 kHz to 2 MHz from the viewpoint of generating minute droplets with an extremely uniform particle size. [Example]

[0073] Examples of the present invention will be described below, but the present invention is not limited to these examples in any way.

[0074] Example 1 -Preparation of prescription solution A- Formulation solution A was prepared by dissolving polylactic acid (PLA-R-001F-SOR, manufactured by Nagase & Co., Ltd.) in dichloromethane as a solvent.

[0075] - Granulation of particle 1 (Rayleigh fission) - The obtained formulation A was ejected from an ejection hole to form droplets using the Rayleigh breakup droplet ejection means shown in Fig. 6, and the solvent was removed from the droplets using the particle manufacturing apparatus shown in Fig. 3 to form particles 1. After granulation, the particles were vacuum dried. The volume average particle size (Dv) of the obtained particles 1 was 16.2 μm and the RSF was 0.72. These were measured using a laser diffraction / scattering particle size distribution analyzer (device name: LA-960, manufactured by Horiba, Ltd.). The average circularity was 0.966, which was measured using a flow particle image analyzer (product name "FPIA (registered trademark)-3000S", manufactured by Sysmex Corporation). The amount of alkaline earth metal was 0.1 ppm, which was measured using a multi-type ICP emission spectrometer (Shimadzu Corporation, "ICPE-9000"). The solvent content of the particles was 0.9%, which was measured using a gas chromatograph (GC-14A, SHIMADZU). The production conditions for the particles are as follows. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 10μm Extrusion pressure of prescription liquid: 0.4MPa ·Excitation frequency: 150kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 40℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0076] Example 2 -Preparation of prescription solution B- Formulation solution B was prepared by dissolving polylactic-co-glycolic acid (PDLG5004, manufactured by Corbion Japan Co., Ltd.) in a mixed solvent of acetonitrile and water in a mass ratio of 9:1.

[0077] - Granulation of particle 2 (Rayleigh fission) - Using the obtained formulation B, particles 2 were granulated in the same manner as in Example 1, except that the particle production conditions were changed as follows. The obtained particles 2 had a volume average particle size (Dv) of 26.9 μm and an RSF of 0.52. The average circularity was 0.981. The amount of alkaline earth metal was 0.1 ppm. The solvent content of the particles was 0.5%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 30μm Extrusion pressure of prescription liquid: 0.18MPa Excitation frequency: 80kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 50℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0078] Example 3 -Preparation of prescription solution C- Formulation C was prepared by dissolving polyhydroxyalkanoate (BP350-15, 3-hydroxybutyrate:3-hydroxyhexanoate ratio=90:10, BLUPHA Co., Ltd.) in a mixed solvent of dichloromethane and ethanol in a mass ratio of 6:4.

[0079] - Granulation of particle 3 (Rayleigh fission) - Using the obtained formulation C, particles 3 were granulated in the same manner as in Example 1, except that the particle production conditions were changed as follows. The obtained particles 3 had a volume average particle size (Dv) of 22.8 μm and an RSF of 0.98. The average circularity was 0.925. The amount of alkaline earth metal was 0.3 ppm. The solvent content of the particles was 0.4%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 10μm Extrusion pressure of prescription liquid: 0.4MPa ·Excitation frequency: 150kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 25℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0080] Example 4 -Preparation of prescription solution D- Formulation D was prepared by dissolving polyhydroxyalkanoate (BP350-15, BLUPHA Co., Ltd.) in a mixed solvent of dimethylformamide and acetone in a mass ratio of 5:5.

[0081] - Granulation of particle 4 (Rayleigh fission) - Using the obtained formulation D, particles 4 were granulated in the same manner as in Example 1, except that the particle production conditions were changed as follows. The obtained particles 4 had a volume average particle size (Dv) of 18.9 μm and an RSF of 0.75. The average circularity was 0.985. The amount of alkaline earth metal was 0.3 ppm. The solvent content of the particles was 0.4%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 15μm Extrusion pressure of prescription liquid: 0.15MPa ·Excitation frequency: 130kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 50℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0082] Example 5 -Preparation of prescription solution E- Formulation E was prepared by dissolving polyhydroxyalkanoate (PHBV, Sigmaaidrich) in dimethylformamide as a solvent.

[0083] - Granulation of particle 5 (Rayleigh fission) - Using the obtained formulation E, particles 5 were granulated in the same manner as in Example 1, except that the particle production conditions were changed as follows. The obtained particles 5 had a volume average particle size (Dv) of 20.9 μm and an RSF of 1.12. The average circularity was 0.982. The amount of alkaline earth metal was 0.2 ppm. The solvent content of the particles was 0.8%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 15μm Extrusion pressure of prescription liquid: 0.15MPa ·Excitation frequency: 130kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 120℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0084] Example 6 -Preparation of prescription solution F- Formulation solution F was prepared by dissolving polyhydroxyalkanoate (BP350-05, BLUPHA Co., Ltd.) in a mixed solvent of dimethylformamide and acetone in a mass ratio of 5:5.

[0085] - Granulation of particle 6 (Rayleigh fission) - Using the obtained formulation F, particles 6 were granulated in the same manner as in Example 1, except that the particle production conditions were changed as follows. The obtained particles 6 had a volume average particle size (Dv) of 21.9 μm and an RSF of 0.91. The average circularity was 0.985. The amount of alkaline earth metal was 0.1 ppm. The solvent content of the particles was 0.8%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 15μm Extrusion pressure of prescription liquid: 0.15MPa ·Excitation frequency: 130kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 50℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0086] (Comparative Example 1) -Granulation of particle 7 (spray drying)- Using formulation D prepared in Example 4, particles 7 were granulated by a spray drying means (rotary disk atomizer, manufactured by Okawara Chemical Engineering Co., Ltd.) under the following particle production conditions. The volume average particle size (Dv) of the obtained particles 7 was 20.9 μm, and the RSF was 1.54. The average circularity was 0.981. The amount of alkaline earth metal was 0.2 ppm. The solvent content of the particles was 0.8%. [Particle manufacturing conditions] ·Spray dryer model: L-8 Rotary disc atomizer speed: 10,000 rpm Prescription liquid feed rate: 2 kg / hour Air flow rate: 50m 3 / h Dry air temperature: 50℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0087] (Comparative Example 2) -Granulation of particle 8 (spray drying)- Using the formulation C prepared in Example 3, particles 8 were granulated by a spray drying means (rotary disk atomizer, manufactured by Okawara Chemical Engineering Co., Ltd.) under the following particle production conditions. The volume average particle size (Dv) of the obtained particles 8 was 19.8 μm, and the RSF was 1.51. The average circularity was 0.932. The amount of alkaline earth metal was 0.2 ppm. The solvent content of the particles was 0.3%. [Particle manufacturing conditions] ·Spray dryer model: L-8 Rotary disc atomizer speed: 10,000 rpm Prescription liquid feed rate: 2 kg / hour Air flow rate: 50m 3 / h Dry air temperature: 50℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0088] (Comparative Example 3) -Preparation of prescription solution G- Polyhydroxyalkanoate (BP350-15, BLUPHA Co., Ltd.) was dissolved in a 5:5 mass ratio mixed solvent of dimethylformamide and acetone in a quartz glass pot mill, and then a dispersion stabilizer (Shiraishi Calcium Co., Ltd., ACTIFORT700, in an amount to give 20 ppm relative to the resin) and 5 mm zirconia beads were added. The mixture was treated on a ball mill rotating stand at a peripheral speed of 100 rpm for 24 hours to prepare formulation solution G.

[0089] - Granulation of particle 9 (Rayleigh fission) - Using the obtained formulation G, particles 9 were granulated in the same manner as in Example 1, except that the particle production conditions were changed as follows. The obtained particles 9 had a volume average particle size (Dv) of 19.2 μm and an RSF of 1.31. The average circularity was 0.985. The amount of alkaline earth metal was 20 ppm. The solvent content of the particles was 0.3%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 15μm Extrusion pressure of prescription liquid: 0.15MPa ·Excitation frequency: 130kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 50℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0090] Comparative Example 4 - Granulation of particle 10 (Rayleigh fission) - Particles 10 were granulated in the same manner as in Example 1 using formulation D prepared in Example 4, except that the particle production conditions were changed as follows. The volume average particle size (Dv) of the obtained particles 10 was 18.1 μm, and the RSF was 1.62. The average circularity was 0.924. The amount of alkaline earth metal was 0.3 ppm. The solvent content of the particles was 2.3%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 15μm Extrusion pressure of prescription liquid: 0.15MPa ·Excitation frequency: 130kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 50℃ Vacuum drying after granulation: Not performed

[0091] Example 7 -Preparation of prescription solution H- Formulation solution H was prepared by dissolving polybutylene adipate terephthalate (TH801T, Chori Co., Ltd.) in dichloromethane as a solvent.

[0092] - Granulation of particle 11 (Rayleigh fission) - Using the obtained formulation H, particles 11 were granulated in the same manner as in Example 1, except that the particle production conditions were changed as follows. The obtained particles 11 had a volume average particle size (Dv) of 19.9 μm and a RSF of 0.89. The average circularity was 0.991. The amount of alkaline earth metal was 0.1 ppm. The solvent content of the particles was 0.7%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 15μm Extrusion pressure of prescription liquid: 0.15MPa ·Excitation frequency: 130kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 50℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0093] Example 8 -Preparation of prescription solution I- Polyhydroxyalkanoate (BP350-15, BLUPHA Co., Ltd.) was mixed with dimethylformamide as a solvent. To adjust the molecular weight of the polyhydroxyalkanoate by thermal decomposition, the mixture was heated to 150°C, stirred for 15 minutes, and then cooled to room temperature. Acetone was added to this solution to prepare Formulation I, which had a dimethylformamide to acetone mass ratio of 5:5.

[0094] - Granulation of particle 12 (Rayleigh fission) - Using the obtained formulation I, particles 12 were granulated in the same manner as in Example 1, except that the particle production conditions were changed as follows. The obtained particles 12 had a volume average particle size (Dv) of 24.4 μm and an RSF of 0.89. The average circularity was 0.922. The amount of alkaline earth metal was 0.2 ppm. The solvent content of the particles was 0.5%. [Particle manufacturing conditions] Discharge hole shape: perfect circle Discharge hole diameter: 15μm Extrusion pressure of prescription liquid: 0.15MPa ·Excitation frequency: 130kHz Excitation voltage: 5V Air flow rate: 50m 3 / h Dry air temperature: 50℃ · Vacuum drying after granulation: Pressure 500 Pa, temperature 30°C, drying time 24 hours

[0095] Table 1 shows the production conditions for particles 1 to 12. In Table 1, "PLA" stands for "polylactic acid." "PLGA" stands for "polylactic-co-glycolic acid." "PHBH" stands for "poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)." "PHBV" stands for "poly(3-hydroxybutyrate-co-3-hydroxyvalerate)." "PBAT" stands for "polybutylene adipate terephthalate."

[0096] [Table 1]

[0097] (Making powder foundation) A mixture was prepared by mixing 10 parts by weight of the resin particle group of Examples 1 to 8 and Comparative Examples 1 to 4 with 21 parts by weight of sericite, 56 parts by weight of muscovite, 0.6 parts by weight of red iron oxide, 1 part by weight of yellow iron oxide, and 0.1 part by weight of black iron oxide as pigments using a Henschel mixer. Separately, a solution was prepared by mixing and dissolving 10 parts by weight of 2-ethylhexanoate as an oily base, 1 part by weight of sorbitan sesquioleate as an emulsifier, and 0.2 parts by weight of a preservative. The mixture and the solution were uniformly mixed, and then 0.1 parts by weight of fragrance was added. The mixture was then uniformly mixed, pulverized, and sieved to prepare a foundation material. This foundation material was compression-molded into a metal dish to produce a powder foundation. Ten panelists spread the resulting powder foundation on their wrists and evaluated its adhesion to the skin and smoothness of spread on the skin according to the following criteria. The results are shown in Table 2. The evaluation results in the table are the average values ​​of the test results of 10 people, and a score of 4.0 or higher was considered a pass. [Evaluation criteria] 5: Very good 4: Good 3: Fairly good 2: Not very good 1: Not good

[0098] [Table 2]

[0099] The results of Examples 1 to 8 show that by using resin particles having a volume average particle size of 5 μm or more and 50 μm or less and a relative span factor (RSF) of 1.2 or less, the cosmetic product has excellent adhesion to the skin and a soft feel on the skin. On the other hand, the results of Comparative Examples 1 to 4 show that when (RSF) exceeds 1.2, at least one of adhesion to the skin and soft feel on the skin is not excellent, making it unsuitable for use in cosmetics.

[0100] The embodiments of the present invention are as follows, for example. <1> Resin particles containing a biodegradable resin, The volume average particle size is 5 μm or more and 50 μm or less, The resin particles are characterized by a relative span factor (RSF) of 1.2 or less. <2> Characterized by an average circularity of greater than 0.980 <1> The resin particles are as described in <3> The biodegradable resin contains at least one of polylactic acid and polylactic-co-glycolic acid copolymer. <1> from <2> The resin particles according to any one of the above items. <4> The biodegradable resin contains polyhydroxyalkanoate. <1> from <3> The resin particles according to any one of the above items. <5> The polyhydroxyalkanoate is characterized in that it is poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). <4> The resin particles are as described in <6> The biodegradable resin contains polybutylene adipate terephthalate. <1> from <5> The resin particles according to any one of the above items. <7> The biodegradable resin is characterized in that its weight average molecular weight is 500,000 or less. <1> from <6> The resin particles according to any one of the above items. <8> The biodegradable resin is characterized in that its weight average molecular weight is 50,000 or less. <1> from <7> The resin particles according to any one of the above items. <9> The amount of alkaline earth metal components contained in the resin particles is 0.05 ppm or more and less than 10 ppm relative to the total mass of the resin particles. <1> from <8> The resin particles according to any one of the above items. <10> The amount of organic solvent contained in the resin particles is 1 ppm or more and less than 1% of the total mass of the resin particles. <1> from <9> The resin particles according to any one of the above items. <11> <1> from <10> The method for producing resin particles according to any one of the above items, a droplet ejection step of ejecting droplets of a particle composition liquid containing the biodegradable resin and a solvent into a gas; and a granulation step of removing the solvent from the droplets to form particles. <12> In the droplet ejection step, vibration is applied to the particle composition liquid, and the particle composition liquid is ejected from an ejection hole. <11> 2. A method for producing resin particles according to claim 1.

[0101] The aforementioned <1> from <10> The resin particles according to any one of the preceding claims, and <11> from <12> The method for producing resin particles according to any one of the above items can solve the above-mentioned problems in the prior art and achieve the object of the present invention. [Explanation of symbols]

[0102] 9, 309 Elastic plate 11 Liquid column resonance droplet ejection means 14, 314 Particle composition liquid 17 Liquid common supply path 18 Liquid column resonance liquid chamber 19 Discharge hole 20 Vibration generating means 21, 321 droplet 300 Resin particle manufacturing equipment 301 Downdraft (Carrying Air Current) 302 Droplet discharge means 312 Air flow passage 313 Particle composition liquid container 315 Liquid Circulation Pump 316 Liquid supply pipe 319 Particle composition liquid storage section 320 Volume change means 322 Liquid return pipe 360 Dry Collection Unit 361 Chamber 362 Particle collection means 363 Particle Reservoir 364 Conveying airflow inlet 365 Conveying airflow outlet 401 Storage section 402 Vibration means 403 Through hole 404 Supply piping 405 Penetration retention mechanism 406 Vibration Generator 407 Conductive Wire 408 Release valve 409 Droplet [Prior art documents] [Patent documents]

[0103] [Patent Document 1] International Publication No. 2008 / 047863 [Patent Document 2] Japanese Patent Publication No. 2021-147330 [Patent Document 3] Japanese Patent Application Laid-Open No. 2005-2302 [Patent Document 4] International Publication No. 2017 / 195642

Claims

1. Resin particles containing a biodegradable resin, The volume average particle size is 5 μm or more and 50 μm or less, Resin particles having a relative span factor (R.S.F.) of 1.2 or less.

2. 2. The resin particles according to claim 1, wherein the average circularity is greater than 0.

980.

3. 2. The resin particles according to claim 1, wherein the biodegradable resin contains at least one of polylactic acid and polylactic-co-glycolic acid copolymer.

4. 2. The resin particles according to claim 1, wherein the biodegradable resin contains polyhydroxyalkanoate.

5. 5. The resin particles according to claim 4, wherein the polyhydroxyalkanoate is poly(3-hydroxybutyrate-co-3-hydroxyhexanoate).

6. 2. The resin particles according to claim 1, wherein the biodegradable resin contains polybutylene adipate terephthalate.

7. 2. The resin particles according to claim 1, wherein the weight average molecular weight of the biodegradable resin is 500,000 or less.

8. 2. The resin particles according to claim 1, wherein the weight average molecular weight of the biodegradable resin is 50,000 or less.

9. 2. The resin particles according to claim 1, wherein the amount of alkaline earth metal components contained in the resin particles is 0.05 ppm or more and less than 10 ppm with respect to the total mass of the resin particles.

10. 2. The resin particles according to claim 1, wherein the amount of the organic solvent contained in the resin particles is 1 ppm or more and less than 1% of the total mass of the resin particles.

11. A method for producing resin particles according to any one of claims 1 to 10, comprising: a droplet ejection step of ejecting droplets of a particle composition liquid containing the biodegradable resin and a solvent into a gas; and a granulation step of removing the solvent from the droplets to form particles.

12. 12. The method for producing resin particles according to claim 11, wherein, in the droplet ejection step, vibrations are applied to the particle composition liquid and the particle composition liquid is ejected from the ejection holes.

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