Droplet forming device and fine particle manufacturing device

Abstract

Provided is a liquid droplet forming device comprising: a liquid chamber; a discharge hole for discharging a raw material liquid which is in the liquid chamber, in the form of droplets; a sealed space forming means; and at least two flow passages. The sealed space forming means is capable of forming a sealed space which can communicate with the liquid chamber via the discharge hole, on the side of the discharge hole opposite the liquid chamber. The at least two flow passages communicate with one another through the sealed space.

Description

[Technical Field]

[0001] The present invention relates to a droplet forming device and a fine particle manufacturing device. This application claims priority based on Japanese Patent Application No. 2020-183144, filed on October 30, 2020, and Japanese Patent Application No. 2021-083324, filed on May 17, 2021, the contents of which are incorporated herein by reference. [Background technology]

[0002] Fine particles with a narrow particle size distribution are used in a variety of applications, such as toner fine particles for electrophotography and spacer particles for liquid crystal panels. Among these, a known device for producing toner fine particles is a manufacturing device that ejects liquid toner material as droplets and granulates them into fine particles of a desired particle size (see, for example, Patent Document 1). The manufacturing device described in Patent Document 1 ejects a raw material liquid, which is the material for the fine particles, from a nozzle as droplets, and removes the solvent from the droplets to produce fine particles with a desired particle size distribution. Summary of the Invention [Problem to be solved by the invention]

[0003] The fine particles having a narrow particle size distribution as described above are also used as materials for tablets and capsules as carriers for physiologically active substances such as pharmaceutical compounds.

[0004] Microparticles for pharmaceutical use must be manufactured in hygienic facilities that comply with Good Manufacturing Practice (GMP). Therefore, the equipment used to manufacture microparticles must be effectively cleaned and kept clean to prevent contamination of different drugs when switching between different types of drugs and to ensure that microparticles with the designed particle size distribution can be manufactured.

[0005] On the other hand, for industrial production of fine particles, it is desirable to efficiently clean the equipment so as not to excessively reduce production efficiency (production amount per unit time).

[0006] The manufacturing apparatus described in Patent Document 1 includes a configuration for cleaning the nozzles, but there is room for further improvement in order to maintain the apparatus in a state suitable for manufacturing without reducing production efficiency, while also effectively cleaning the apparatus.

[0007] The above-mentioned problem is not limited to pharmaceuticals. The need to prevent contamination by foreign matter and maintain conditions suitable for producing desired particles is common in the technical field of microparticle production.

[0008] The present invention has been made in consideration of the above circumstances, and aims to provide a droplet forming device that can efficiently and effectively clean nozzles, and a particle manufacturing device that is equipped with the droplet forming device and is capable of manufacturing high-quality particles. [Means for solving the problem]

[0009] In order to solve the above problems, one aspect of the present invention provides a droplet forming device comprising a liquid chamber, an ejection hole that ejects raw material liquid in the liquid chamber as droplets, a sealed space forming means, and at least two flow paths, wherein the sealed space forming means is capable of forming a sealed space on the opposite side of the ejection hole from the liquid chamber that is connected to the liquid chamber via the ejection hole, and the at least two flow paths are connected to each other via the sealed space. [Effects of the Invention]

[0010] According to the present invention, it is possible to provide a droplet forming device that can efficiently and effectively clean a nozzle, and also to provide a particle manufacturing device that is equipped with the droplet forming device and is capable of manufacturing high-quality particles. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is an explanatory diagram of a droplet forming device. [Figure 2] FIG. 2 is an explanatory diagram showing an example of the configuration of the switching means 26. As shown in FIG. [Figure 3]FIG. 3 is an explanatory diagram illustrating the operation of the droplet forming device 1. [Figure 4] FIG. 4 is an explanatory diagram illustrating the operation of the droplet forming device 1. [Figure 5] FIG. 5 is an explanatory diagram illustrating the operation of the droplet forming device 1. [Figure 6] FIG. 6 is an explanatory diagram illustrating the operation of the droplet forming device 1. [Figure 7] FIG. 7 is an explanatory diagram illustrating the operation of the droplet forming device 1. [Figure 8] FIG. 8 is an explanatory diagram illustrating the operation of the droplet forming device 1. [Figure 9] FIG. 9 is an explanatory diagram of a droplet forming device and a fine particle manufacturing device according to the second embodiment. [Figure 10] FIG. 10 is an explanatory diagram of a droplet forming device according to the second embodiment. [Figure 11] FIG. 11 is an explanatory diagram of a droplet forming device according to the second embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0012] [First embodiment] The droplet forming device according to the first embodiment will be described below with reference to Figures 1 to 8. In all of the following figures, the dimensions and proportions of the components have been changed as appropriate to make the drawings easier to understand.

[0013] 《Droplet formation device》 The droplet forming device of this embodiment has a discharge unit that discharges droplets of the raw material liquid, and a cleaning unit that cleans the discharge unit.

[0014] The ejection section may employ, for example, any of the following (1) to (3), which are known configurations for devices that eject droplets. (1) A configuration using a "volume changing means" that changes the volume of the liquid storage section using vibration (2) A configuration using a "constriction generating means" that applies vibration to the liquid storage section while discharging the liquid from multiple discharge holes provided in the liquid storage section, causing the liquid to change from a columnar shape to a constricted state and then to droplets. (3) A configuration using a "nozzle vibration means" that vibrates a thin film with an ejection hole (nozzle) formed therein.

[0015] <Volume Changing Means> There are no particular restrictions on the volume-changing 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, piezoelectric elements (sometimes called "piezo elements") that expand and contract when voltage is applied, electrothermal conversion elements such as heating resistors, etc.

[0016] <Means for generating constriction> An example of a constriction generating means is a means using the technology described in JP 2007-199463 A. JP 2007-199463 A devised a configuration in which a liquid storage portion is vibrated by a vibration means using a piezoelectric element in contact with a part of the liquid storage portion while raw material liquid is released from a plurality of nozzles provided in the liquid storage portion, causing the raw material fluid to change from a columnar state to a constricted state and then to become droplets.

[0017] <Nozzle Vibration Means> An example of a nozzle vibration means is a means using the technology described in JP 2008-292976 A. JP 2008-292976 A includes a thin film provided in a liquid storage section and having a plurality of nozzles formed therein, and piezoelectric elements arranged around the thin film within a deformable region thereof to vibrate the thin film, thereby discharging the raw material liquid from the plurality of nozzles and forming droplets.

[0018] As an example, a droplet forming device employing a discharge section having a constriction generating means will be described below with reference to the drawings.

[0019] Fig. 1 is an explanatory diagram of a droplet forming device. As shown in Fig. 1, the droplet forming device 1 of this embodiment includes a discharge unit 10 and a cleaning unit 20. The droplet forming device 1 may also include a control unit 50 that controls the operation of each unit.

[0020] <Discharge part> The ejection unit 10 ejects droplets of a raw material liquid, which will be described later. The ejection unit 10 has a liquid chamber 10A that stores the raw material liquid, and an ejection hole (nozzle) 102x that communicates with the liquid chamber 10A. The raw material liquid stored in the liquid chamber 10A is ejected through the ejection hole 102x and is formed into a spherical shape in the gas phase due to the surface tension of the raw material liquid.

[0021] The ejection unit 10 includes an ejection head 100 having a liquid chamber 10A and an ejection hole 102x, and an ejection unit main body 110 to which the ejection head 100 is connected. The ejection head 100 may be configured to be detachable from the ejection unit main body 110.

[0022] The ejection head 100 is not particularly limited as long as it has the liquid chamber 10A, and the shape, size, etc. can be selected appropriately depending on the purpose.

[0023] The ejection head 100 has a head main body 101 in which a liquid chamber 10A is provided, and a nozzle plate 102 that forms part of the wall surface of the liquid chamber 10A.

[0024] The nozzle plate 102 has a plurality of ejection holes 102x. The cross-sectional shape and size of the ejection holes 102x can be selected appropriately.

[0025] The cross-sectional shape of the discharge hole 102x is not particularly limited and can be appropriately selected depending on the purpose. For example, (1): A tapered shape in which the opening diameter becomes smaller from the inside (liquid chamber side) to the outside (liquid ejection side) (2) A rounded shape with a narrower opening diameter from the inside (liquid chamber side) to the outside (liquid ejection side) (3) A nozzle with a shape in which the opening diameter narrows at a certain nozzle angle from the inside (liquid chamber side) to the outside (liquid ejection side). (4): Combination of the shape of (1) and the shape of (2) Among these, the shape (3) is preferable because it maximizes the pressure applied to the liquid at the discharge holes 102x.

[0026] The nozzle angle in the shape (3) is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 60° or more and 90° or less. If the nozzle angle is 60° or more, pressure is easily applied to the liquid, making it easier to process. If the nozzle angle is 90° or less, pressure is applied to the discharge holes, making it possible to stabilize the discharge of droplets. Therefore, it is preferable to set the maximum nozzle angle to 90°.

[0027] The size of the discharge holes 102x is not particularly limited and can be appropriately selected depending on the purpose. For example, the diameter of the discharge holes 102x is preferably 5 μm or more and 100 μm or less.

[0028] The ejection head 100 is preferably configured to be disassembled into a head main body 101 and a nozzle plate 102. In an ejection head 100 configured in this way, the liquid chamber 10A can be kept clean by disassembling and cleaning as necessary.

[0029] The ejection head 100 has a vibration unit 15 that applies vibrations to the raw material liquid stored in the liquid chamber 10A. A piezoelectric element is generally used as the vibration unit 15. There are no particular limitations on the piezoelectric element, and the shape, size, and material can be selected appropriately. For example, a piezoelectric element used in a conventional inkjet ejection method can be suitably used.

[0030] 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.

[0031] 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.

[0032] The ejection head 100 can turn the raw material liquid into droplets by ejecting the raw material liquid from the liquid chamber 10A through the ejection holes 102x while applying vibrations to the raw material liquid in the liquid chamber 10A using the vibration unit 15.

[0033] Furthermore, the discharge unit 10 has a raw material liquid supply unit 19 that supplies the raw material liquid to the discharge head 100. The raw material liquid supply unit 19 has a raw material liquid tank 191 that stores the raw material liquid. The means for supplying the raw material liquid from the raw material liquid tank 191 to the liquid chamber 10A may be a pump provided in the piping path, or may be a pressure means that increases the internal pressure of the raw material liquid tank 191 in order to pressure-feed the raw material liquid.

[0034] -Raw material liquid- The raw material liquid contains a base material, and further contains a solvent and other components as required.

[0035] --Base material-- The substrate is a material that serves as the base for constituting the particles. Therefore, it is preferably solid at room temperature. The substrate is not particularly limited as long as it is not a substance that adversely affects the physiologically active substance contained therein, and may be a low-molecular-weight substance or a high-molecular-weight substance. However, since the particles of the present invention are preferably particles that are applied to living organisms, the substrate is preferably a substance that is not toxic to living organisms. The low-molecular-weight substance is preferably a compound with a weight-average molecular weight of less than 15,000. The high-molecular-weight substance is preferably a compound with a weight-average molecular weight of 15,000 or more. As mentioned above, the substrate may be one type or two or more types, and any of the substrates described below may be used in combination.

[0036] -Low molecular weight substances- The low-molecular-weight substance is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include lipids, sugars, cyclodextrins, amino acids, organic acids, etc. These may be used alone or in combination of two or more.

[0037] --Lipids-- The lipids are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include medium- or long-chain monoglycerides, medium- or long-chain diglycerides, medium- or long-chain triglycerides, phospholipids, vegetable oils (e.g., soybean oil, avocado oil, squalene oil, sesame oil, olive oil, corn oil, rapeseed oil, safflower oil, sunflower oil, etc.), fish oil, seasoning oil, water-insoluble vitamins, fatty acids, mixtures thereof, and derivatives thereof. These lipids may be used alone or in combination of two or more.

[0038] --Sugars-- The sugars are not particularly limited and can be selected appropriately depending on the purpose, and examples thereof include monosaccharides and polysaccharides such as glucose, mannose, idose, galactose, fucose, ribose, xylose, lactose, sucrose, maltose, trehalose, turanose, raffinose, maltotriose, acarbose, cyclodextrins, amylose (starch), and cellulose, as well as sugar alcohols (polyols) such as glycerin, sorbitol, lactitol, maltitol, mannitol, xylitol, and erythritol, and derivatives thereof. These sugars may be used alone or in combination of two or more.

[0039] --Cyclodextrins-- The cyclodextrins are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include hydroxypropyl-β-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, α-cyclodextrin, cyclodextrin derivatives, etc. These cyclodextrins may be used alone or in combination of two or more.

[0040] --Amino acids-- The amino acids are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include valine, lysine, leucine, threonine, isoleucine, asparagine, glutamine, phenylalanine, aspartic acid, serine, glutamic acid, methionine, arginine, glycine, alanine, tyrosine, proline, histidine, cysteine, tryptophan, and derivatives thereof. These amino acids may be used alone or in combination of two or more.

[0041] --Organic acids-- The organic acids are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include adipic acid, ascorbic acid, citric acid, fumaric acid, gallic acid, glutaric acid, lactic acid, malic acid, maleic acid, succinic acid, tartaric acid, and derivatives thereof. These organic acids may be used alone or in combination of two or more.

[0042] -High molecular weight substances- The high-molecular-weight substance is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include water-soluble cellulose, polyalkylene glycol, poly(meth)acrylamide, poly(meth)acrylic acid, poly(meth)acrylic acid ester, polyallylamine, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, biodegradable polyester, polyglycolic acid, polyamino acid, gelatin, proteins such as fibrin, polysaccharides, and derivatives thereof. These high-molecular-weight substances may be used alone or in combination of two or more.

[0043] --Water-soluble cellulose-- The water-soluble cellulose is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include alkyl celluloses such as methyl cellulose and ethyl cellulose; hydroxyalkyl celluloses such as hydroxyethyl cellulose and hydroxypropyl cellulose; and hydroxyalkyl alkyl celluloses such as hydroxyethyl methyl cellulose and hydroxypropyl methyl cellulose. These water-soluble celluloses may be used alone or in combination of two or more. Among these water-soluble celluloses, hydroxypropyl cellulose and hydroxypropyl methyl cellulose are preferred, and hydroxypropyl cellulose is more preferred, because of their high biocompatibility and high solubility in the solvent used to produce the particles.

[0044] ---Hydroxypropyl cellulose--- Hydroxypropyl cellulose is commercially available in a variety of products with different viscosities, all of which can be used in the base material of the present invention. The viscosity of a 2% by mass aqueous solution of hydroxypropyl cellulose (20°C) is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 2.0 mPa·s (centipoise, cps) or more and 4,000 mPa·s (centipoise, cps) or less.

[0045] The viscosity of hydroxypropyl cellulose is considered to depend on the weight-average molecular weight, degree of substitution, and molecular weight of hydroxypropyl cellulose. The weight-average molecular weight of hydroxypropyl cellulose is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 15,000 or more and 400,000 or less. The weight-average molecular weight can be measured, for example, by gel permeation chromatography (GPC).

[0046] Commercially available hydroxypropyl cellulose products are not particularly limited and can be appropriately selected depending on the purpose. Examples include HPC-SSL, which has a molecular weight of 15,000 to 30,000 and a viscosity of 2.0 to 2.9 mPa·s; HPC-SL, which has a molecular weight of 30,000 to 50,000 and a viscosity of 3.0 to 5.9 mPa·s; HPC-L, which has a molecular weight of 55,000 to 70,000 and a viscosity of 6.0 to 10.0 mPa·s; HPC-M, which has a molecular weight of 110,000 to 150,000 and a viscosity of 150 to 400 mPa·s; and HPC-H, which has a molecular weight of 250,000 to 400,000 and a viscosity of 1,000 to 4,000 mPa·s (all manufactured by Nippon Soda Co., Ltd.). These hydroxypropyl celluloses may be used alone or in combination of two or more. Among these hydroxypropyl celluloses, HPC-SSL having a molecular weight of 15,000 to 30,000 and a viscosity of 2.0 to 2.9 mPa·s is preferred. In the above commercially available products, the molecular weight is measured using gel permeation chromatography (GPC), and the viscosity is measured using a 2% by weight aqueous solution (20°C).

[0047] The content of hydroxypropyl cellulose is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 50% by mass or more, more preferably 50% by mass or more and 99% by mass or less, even more preferably 75% by mass or more and 99% by mass or less, and particularly preferably 80% by mass or more and 99% by mass or less, relative to the mass of the base material.

[0048] --Polyalkylene glycol-- The polyalkylene glycol is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include polyethylene glycol (PEG), polypropylene glycol, polybutylene glycol, and copolymers thereof. These polyalkylene glycols may be used alone or in combination of two or more.

[0049] --Poly(meth)acrylamide-- The poly(meth)acrylamide is not particularly limited and can be appropriately selected depending on the purpose. Examples include polymers of monomers such as N-methyl(meth)acrylamide, N-ethyl(meth)acrylamide, N-propyl(meth)acrylamide, N-butyl(meth)acrylamide, N-benzyl(meth)acrylamide, N-hydroxyethyl(meth)acrylamide, N-phenyl(meth)acrylamide, N-tolyl(meth)acrylamide, N-(hydroxyphenyl)(meth)acrylamide, N-(sulfamoylphenyl)(meth)acrylamide, N-(phenylsulfonyl)(meth)acrylamide, N-(tolylsulfonyl)(meth)acrylamide, N,N-dimethyl(meth)acrylamide, N-methyl-N-phenyl(meth)acrylamide, and N-hydroxyethyl-N-methyl(meth)acrylamide. These monomers may be polymerized singly or in combination of two or more. These polymers may be used singly or in combination of two or more.

[0050] --Poly(meth)acrylic acid-- The poly(meth)acrylic acid is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include homopolymers such as polyacrylic acid and polymethacrylic acid, copolymers such as acrylic acid-methacrylic acid copolymer, etc. These poly(meth)acrylic acids may be used alone or in combination of two or more.

[0051] --Poly(meth)acrylic acid ester-- The poly(meth)acrylic acid ester is not particularly limited and can be appropriately selected depending on the purpose. Examples include polymers of monomers such as ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, propylene glycol di(meth)acrylate, glycerol poly(meth)acrylate, polyethylene glycol (meth)acrylate, trimethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, and 1,3-butylene glycol di(meth)acrylate. These monomers may be polymerized alone or in combination of two or more. These polymers may be used alone or in combination of two or more.

[0052] --Polyallylamine-- The polyallylamine is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include diallylamine, triallylamine, etc. These polyallylamines may be used alone or in combination of two or more.

[0053] --Polyvinylpyrrolidone-- As the polyvinylpyrrolidone, commercially available products can be used. There are no particular limitations on the commercially available polyvinylpyrrolidone products, and they can be appropriately selected depending on the purpose. Examples include Plasdone C-15 (manufactured by ISP TECHNOLOGIES), Kollidon VA64, Kollidon K-30, Kollidon CL-M (all manufactured by KAWARLAL), and Kollicoat IR (manufactured by BASF). These polyvinylpyrrolidones may be used alone or in combination of two or more.

[0054] --Polyvinyl alcohol-- The polyvinyl alcohol is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include silanol-modified polyvinyl alcohol, carboxyl-modified polyvinyl alcohol, acetoacetyl-modified polyvinyl alcohol, etc. These polyvinyl alcohols may be used alone or in combination of two or more.

[0055] --Polyvinyl acetate-- The polyvinyl acetate is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include vinyl acetate-crotonic acid copolymer, vinyl acetate-itaconic acid copolymer, etc. These polyvinyl acetates may be used alone or in combination of two or more.

[0056] --Biodegradable polyester-- The biodegradable polyester is not particularly limited and can be appropriately selected depending on the purpose. Examples include polylactic acid; poly-ε-caprolactone; succinate polymers such as polyethylene succinate, polybutylene succinate, and polybutylene succinate adipate; polyhydroxyalkanoates such as polyhydroxypropionate, polyhydroxybutyrate, and polyhydroxyparate; and polyglycolic acid. These biodegradable polyesters may be used alone or in combination of two or more. Among these, polylactic acid is preferred because of its high biocompatibility and the ability to slowly release the physiologically active substances contained therein.

[0057] ---Polylactic acid--- The weight average molecular weight of polylactic acid is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 5,000 to 100,000, more preferably 10,000 to 70,000, even more preferably 10,000 to 50,000, and particularly preferably 10,000 to 30,000.

[0058] The content of polylactic acid is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 50% by mass or more, more preferably 50% by mass or more and 99% by mass or less, even more preferably 75% by mass or more and 99% by mass or less, and particularly preferably 80% by mass or more and 99% by mass or less, relative to the mass of the base material.

[0059] ---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 polyglycolic acids may be used alone or in combination. Among these, lactic acid-glycolic acid copolymer is preferred because of its high biocompatibility, ability to release physiologically active substances in a sustained release manner, and ability to preserve the physiologically active substances contained therein for a long period of time.

[0060] 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, even more preferably 3,000 to 50,000, and particularly preferably 5,000 to 10,000.

[0061] 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.

[0062] The content of the lactic acid / glycolic acid copolymer is not particularly limited and can be selected appropriately depending on the purpose, but is preferably 50% by mass or more, more preferably 50% by mass to 99% by mass, even more preferably 75% by mass to 99% by mass, and particularly preferably 80% by mass to 99% by mass, based on the mass of the base material.

[0063] --Polyamino acids-- The polyamino acid is not particularly limited and can be appropriately selected depending on the purpose. The polyamino acid may be a polymer obtained by polymerizing any combination of the amino acids exemplified in the above amino acid section, but is preferably a polymer obtained by polymerizing a single amino acid. Preferred polyamino acids include, for example, amino acid homopolymers such as poly-α-glutamic acid, poly-γ-glutamic acid, polyaspartic acid, polylysine, polyarginine, polyornithine, and polyserine, or copolymers thereof. These polyamino acids may be used alone or in combination of two or more.

[0064] --gelatin-- The gelatin is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include lime-processed gelatin, acid-processed gelatin, gelatin hydrolysate, gelatin enzyme dispersion, and derivatives thereof. These gelatins may be used alone or in combination of two or more.

[0065] The natural dispersant polymer used in the gelatin derivative is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include proteins, polysaccharides, nucleic acids, etc. These also include copolymers of natural dispersant polymers or synthetic dispersant polymers. These natural dispersant polymers may be used alone or in combination of two or more.

[0066] Gelatin derivatives refer to gelatin that has been derivatized by covalently bonding a hydrophobic group to the gelatin molecule. The hydrophobic group is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include polyesters such as polylactic acid, polyglycolic acid, and poly-ε-caprolactone; lipids such as cholesterol and phosphatidylethanolamine; alkyl groups, aromatic groups containing a benzene ring; heteroaromatic groups, and mixtures thereof.

[0067] The protein is not particularly limited as long as it does not adversely affect the physiological activity of the physiologically active substance, and can be appropriately selected depending on the purpose, and examples thereof include collagen, fibrin, albumin, etc. These may be used alone or in combination of two or more.

[0068] The polysaccharide is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include chitin, chitosan, hyaluronic acid, alginic acid, starch, pectin, etc. These polysaccharides may be used alone or in combination of two or more.

[0069] The substrate is preferably a substance that allows particles containing the substrate to be contained in pharmaceutical preparations, functional foods, functional cosmetics, etc., and therefore, among the above materials, it is preferable that the substrate be a substance that is not biotoxic, particularly a biodegradable substance such as a biodegradable polymer.

[0070] --solvent-- The solvent is not particularly limited and can be appropriately selected depending on the purpose, but a solvent capable of dissolving or dispersing a poorly water-soluble compound or a pharmaceutically acceptable salt thereof is preferred.

[0071] Examples of solvents include aliphatic halogenated hydrocarbons (e.g., dichloromethane, dichloroethane, chloroform, etc.), alcohols (e.g., methanol, ethanol, propanol, 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, etc.), and amides (e.g., dimethylformamide, dimethylacetamide, etc.). These may be used alone or in combination of two or more. Among these, aliphatic halogenated hydrocarbons, alcohols, ketones, or mixed solvents thereof are preferred from the viewpoint of solubility, and dichloromethane, 1,4-dioxane, methanol, ethanol, acetone, or mixed solvents thereof are more preferred.

[0072] 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 total amount of the raw material solution. A solvent content of 70% by mass or more and 99.5% by mass or less is advantageous in terms of production stability in terms of the solubility of the material and the solution viscosity.

[0073] --Other ingredients-- The other components are not particularly limited and can be selected appropriately depending on the purpose. Examples of other ingredients include water, excipients, flavoring agents, disintegrants, fluidizing agents, adsorbents, lubricants, odorants, surfactants, flavorings, colorants, antioxidants, masking agents, antistatic agents, wetting agents, etc. These ingredients may be used alone or in combination of two or more.

[0074] The excipient is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include lactose, sucrose, mannitol, glucose, fructose, maltose, erythritol, maltitol, xylitol, palatinose, trehalose, sorbitol, crystalline cellulose, talc, anhydrous silicic acid, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, etc. These excipients may be used alone or in combination of two or more.

[0075] The flavoring agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include L-menthol, sucrose, D-sorbitol, xylitol, citric acid, ascorbic acid, tartaric acid, malic acid, aspartame, acesulfame potassium, thaumatin, sodium saccharin, dipotassium glycyrrhizinate, sodium glutamate, 5'-sodium inosinate, 5'-sodium guanylate, etc. These flavoring agents may be used alone or in combination of two or more.

[0076] The disintegrant is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include low-substituted hydroxypropyl cellulose, carmellose, carmellose calcium, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, hydroxypropyl starch, corn starch, etc. These disintegrants may be used alone or in combination of two or more.

[0077] The fluidizing agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include light anhydrous silicic acid, hydrous silicon dioxide, talc, etc. These fluidizing agents may be used alone or in combination of two or more.

[0078] As the light anhydrous silicic acid, commercially available products can be used. There are no particular limitations on the commercially available light anhydrous silicic acid, and it can be appropriately selected depending on the purpose, and examples thereof include Adsolider 101 (manufactured by Freund Corporation: average pore diameter: 21 nm).

[0079] Commercially available products can be used as the adsorbent. There are no particular limitations on the commercially available adsorbent, and it can be appropriately selected depending on the purpose. Examples include trade name: Carplex (component name: synthetic silica, registered trademark of DSL. Japan Co., Ltd.), trade name: Aerosil (registered trademark of Nippon Aerosil Co., Ltd.) 200 (component name: hydrophilic fumed silica), trade name: Sylysia (component name: amorphous silicon dioxide, registered trademark of Fuji Silysia Chemical Co., Ltd.), and trade name: Alkamac (component name: synthetic hydrotalcite, registered trademark of Kyowa Chemical Co., Ltd.). These adsorbents may be used alone or in combination of two or more.

[0080] The lubricant is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include magnesium stearate, calcium stearate, sucrose fatty acid ester, sodium stearyl fumarate, stearic acid, polyethylene glycol, talc, etc. These lubricants may be used alone or in combination of two or more.

[0081] The flavoring agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include trehalose, malic acid, maltose, potassium gluconate, anise essential oil, vanilla essential oil, cardamom essential oil, etc. These flavoring agents may be used alone or in combination of two or more.

[0082] The surfactant is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include polysorbates such as polysorbate 80, polyoxyethylene-polyoxypropylene copolymers, sodium lauryl sulfate, etc. These surfactants may be used alone or in combination of two or more.

[0083] The fragrance is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include lemon oil, orange oil, peppermint oil, etc. These fragrances may be used alone or in combination of two or more.

[0084] The coloring agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include titanium oxide, Food Yellow No. 5, Food Blue No. 2, red ferric oxide, yellow ferric oxide, etc. These coloring agents may be used alone or in combination of two or more.

[0085] The antioxidant is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include sodium ascorbate, L-cysteine, sodium sulfite, and vitamin E. These antioxidants may be used alone or in combination of two or more.

[0086] The masking agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include titanium oxide, etc. These masking agents may be used alone or in combination of two or more.

[0087] The antistatic agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include talc, titanium oxide, etc. These antistatic agents may be used alone or in combination of two or more.

[0088] The wetting agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include polysorbate 80, sodium lauryl sulfate, sucrose fatty acid ester, macrogol, hydroxypropyl cellulose (HPC), etc. These wetting agents may be used alone or in combination of two or more.

[0089] The raw material liquid may be a solution in which a physiologically active substance is dissolved in a solvent or a dispersion in which a physiologically active substance is dispersed in a dispersion medium. The raw material liquid may not contain a solvent as long as it is liquid under the conditions for ejection, or may be a liquid in which the solid content contained in the raw material liquid is in a molten state.

[0090] <Cleaning section> The cleaning section 20 has a sealed space forming means 21 and a flow section 22 .

[0091] The sealed space forming means 21 is capable of liquid-tightly forming a sealed space 21A outside the ejection part 10, which communicates with the liquid chamber 10A via the ejection holes 102x. More specifically, the sealed space forming means 21 has a recess 21x on the side facing the ejection head 100, and an upper end 21a of the side wall surrounding the recess 21x is in liquid-tight contact with the lower surface 100a of the ejection head 100. The space surrounded by the recess 21x and the lower surface 100a is the sealed space 21A. The term "sealed" in "sealed" refers to the liquid-tight contact between the upper end 21a and the lower surface 100a, which prevents liquid leakage from the contact area.

[0092] The sealed space forming means 21 may have an O-ring or packing (not shown) at the upper end portion 21a.

[0093] The sealed space forming means 21 is configured to be detachable from the lower surface 100a.

[0094] The flow portion 22 causes the cleaning liquid to flow through the liquid chamber 10A and the sealed space 21A, cleaning the outer wall and the inner wall of the liquid chamber 10A.

[0095] As the cleaning liquid, a polar organic solvent can be used, and alcohols such as methanol and ethanol, and ketones such as acetone and methyl ethyl ketone can be preferably used. As the cleaning liquid, the same types of liquids as the solvents that can be contained in the raw material liquid can be used.

[0096] The flow section 22 has a cleaning liquid supply section 23, a waste liquid discharge section 24, a first flow path 251, a second flow path 252, a third flow path 253, a fourth flow path 254, and a switching means 26. Two flow paths formed by combining one of the first flow path 251 and the second flow path 252 with one of the third flow path 253 and the fourth flow path 254, or two flow paths formed by the third flow path 253 and the fourth flow path 254, correspond to the "at least two flow paths" in the present invention. The first flow path 251, the second flow path 252, the third flow path 253, and the fourth flow path 254 are formed by through holes formed in the discharge head 100 and pipes connected to the discharge head 100.

[0097] The cleaning liquid supply unit 23 supplies cleaning liquid to the liquid chamber 10A and the sealed space 21A. The cleaning liquid supply unit 23 has a cleaning liquid tank 231 that stores cleaning liquid. The means for supplying cleaning liquid from the cleaning liquid tank 231 to the liquid chamber 10A and the sealed space 21A may be a pump provided in the piping path, or may be a pressure applying means for increasing the internal pressure of the cleaning liquid tank 231 in order to pressure-feed the cleaning liquid.

[0098] The waste liquid discharge unit 24 discharges waste liquid generated by cleaning the liquid chamber 10A and the sealed space 21A. The waste liquid discharge unit 24 has a waste liquid tank 241 that stores waste liquid. The means for discharging the waste liquid from the liquid chamber 10A and the sealed space 21A to the waste liquid tank 241 may be a pump provided in the piping path, or may also be a pressurizing means provided in the cleaning liquid supply unit 23.

[0099] The first flow path 251 and the second flow path 252 are connected to the liquid chamber 10A. The first flow path 251 and the second flow path 252 are connected to the cleaning liquid supply unit 23 and the waste liquid discharge unit 24 via the switching means 26, respectively.

[0100] The third flow path 253 and the fourth flow path 254 are provided at positions that allow them to be connected to the sealed space 21A when the sealed space 21A is formed by the sealed space forming means 21. The third flow path 253 and the fourth flow path 254 are connected to the cleaning liquid supply part 23 and the waste liquid discharge part 24 via the switching means 26, respectively.

[0101] The switching means 26 is connected to the raw material liquid supply unit 19, the cleaning liquid supply unit 23, and the waste liquid discharge unit 24, and switches the flow directions of the raw material liquid, the cleaning liquid, and the waste liquid.

[0102] Fig. 2 is an explanatory diagram showing an example of the configuration of the switching means 26. As shown in Fig. 2, the switching means 26 has switching valves SV1-SV10. For each switching valve, the ON control path is indicated by a dashed line, and the OFF control path is indicated by a solid line.

[0103] In addition, in the switching valves SV1, SV4, SV6, and SV8, the piping is closed when the valves are turned off. As a result, by turning off each switching valve, the first flow path 251, the second flow path 252, the third flow path 253, and the fourth flow path 254 can be closed, respectively.

[0104] 2 denote pressurizing means for causing pressurized gas to flow in the tank and piping, respectively. The pressurizing means applies pressure to the first flow path 251, the second flow path 252, the third flow path 253, the fourth flow path 254, and the discharge hole. The pressure applied to each flow path and discharge hole can be measured by a pressure measuring device 259 installed in the first flow path 251. It is preferable to install the pressure measuring device 259 in the first flow path as close to the discharge hole as possible. Furthermore, a pressure measuring device 260 may be installed in the third flow path 253 to measure the pressure in the sealed space 21A.

[0105] In the switching means 26 shown in FIG. 2, for example, when raw material liquid L1 is supplied from the raw material liquid tank 191 to the first flow path 251 and droplets are ejected from the ejection hole, it is understood that the switching valves SV1, SV2, and SV3 are controlled to be ON and the remaining switching valves are all controlled to be OFF, and the raw material liquid tank 191 is pressurized from the pressurizing means P1.

[0106] In addition, by appropriately switching the switching valves, the flow paths through which the raw material liquid L1, the cleaning liquid L2, and the waste liquid L3 flow can be appropriately switched.

[0107] A cleaning liquid tank 231 storing the cleaning liquid L2 and a raw material liquid tank 191 storing the raw material liquid L1 are switchably connected to the first flow path 251. This reduces the number of pipes and simplifies the device configuration.

[0108] <Control Unit> 1 controls the operation of each component of the discharge unit 10 and the cleaning unit 20. The control unit 50 may be a dedicated terminal provided in the droplet forming device 1, or may be a general-purpose external PC.

[0109] 3 to 8 are explanatory diagrams illustrating the operation of the droplet forming device 1. The droplet forming device 1 can form droplets by ejecting the raw material liquid, and can also easily clean the ejection part 10 from dirt caused by the raw material liquid without decomposing it.

[0110] In the following description of the operation, the flow of liquid will be explained while appropriately showing the control state of the switching valve included in the switching means 26 shown in Figure 2. The operation of each part described below is based on a control signal supplied from the control unit 50.

[0111] 3, in the droplet forming device 1, the switching valve SV4 is controlled to OFF to close the second flow path 252, and the switching valves SV1, SV2, and SV3 are controlled to ON, and the raw material liquid L1 is supplied from the raw material liquid supply unit 19 to the first flow path 251. As a result, the raw material liquid L1 is supplied to the liquid chamber 10A of the ejection head 100 and ejected from the ejection holes 102x.

[0112] At this time, the raw material liquid L1 is supplied while vibration is being generated in the vibration unit 15, so that the raw material liquid L1 is discharged as droplets D from the discharge holes 102x.

[0113] When the droplets D are repeatedly ejected as described above, some of the solid content contained in the raw material liquid L1 may precipitate on the outer wall of the liquid chamber 10A (the outer surface 102a of the nozzle plate 102) and the inner wall of the liquid chamber 10A (the inner surface 102b of the nozzle plate 102), causing stains W1 and W2 to adhere.

[0114] The contaminants W1 and W2 may be mixed into particles produced using the droplet forming device 1, degrading the quality. Furthermore, if the contaminants W1 and W2 clog the discharge holes 102x, the particle diameter of the formed droplets D may not be the set size. Furthermore, if the contaminants W1 and W2 clog the discharge holes 102x, the discharge amount of the droplets D may decrease, resulting in a decrease in productivity.

[0115] In the droplet forming device 1, the cleaning unit 20 can be used to easily clean the discharge unit 10 from such stains.

[0116] (First cleaning (discharge hole cleaning)) 4, the sealed space forming means 21 is brought into contact with the lower surface 100a of the ejection head 100 to form the sealed space 21A. Next, the switching valves SV4 and SV6 are controlled to be OFF, and the second flow path 252 and the third flow path 253 are closed.

[0117] In this state, the other switching valves are controlled to supply the cleaning liquid L2 from the cleaning liquid supply unit 23 to the first flow path 251. The cleaning liquid L2 is supplied from the first flow path 251 to the liquid chamber 10A, and further supplied to the sealed space 21A via the discharge hole 102x.

[0118] The waste liquid L3 discharged from the sealed space 21A is discharged to the waste liquid tank 241 via the fourth flow path 254.

[0119] This allows the cleaning liquid to flow from inside the liquid chamber 10A to outside the liquid chamber 10A, cleaning the liquid chamber 10A and the sealed space 21A. The flow of the cleaning liquid L2 described above causes the dirt W1 that is mainly attached to the outer surface 102a to float up or peel off from the outer surface 102a.

[0120] (Second cleaning (external surface cleaning)) 5, the switching valve SV4 is controlled to be OFF to close the second flow path 252. In this state, the other switching valves are controlled to supply the cleaning liquid L2 from the cleaning liquid supply unit 23 to the first flow path 251 and the third flow path 253. As a result, the cleaning liquid L2 is supplied from the first flow path 251 to the liquid chamber 10A, and further supplied from the third flow path 253 to the sealed space 21A.

[0121] Furthermore, the waste liquid L3 discharged from the sealed space 21A is discharged to the waste liquid tank 241 via the fourth flow path 254. This makes it possible to wash away the dirt W1 that is mainly attached to the outer surface 102a.

[0122] The cleaning liquid supply unit 23 may have a first supply unit that supplies the cleaning liquid L2 and a second supply unit that supplies the cleaning liquid L2 at a higher pressure than the first supply unit, and may be configured so that the cleaning liquid L2 can be supplied independently from the first supply unit and the second supply unit. Using a cleaning liquid supply unit configured in this way, the cleaning liquid L2 may be supplied from the second supply unit to the first flow path 251, and the cleaning liquid L2 may be supplied from the first supply unit to the third flow path 253.

[0123] The relatively high-pressure cleaning liquid L2 flows from the first flow path 251 through the liquid chamber 10A and the discharge hole 102x into the sealed space 21A. This prevents the cleaning liquid L2 in the sealed space 21A from flowing into the liquid chamber 10A, and prevents the dirt W1 on the outer surface 102a from flowing into the liquid chamber 10A.

[0124] In the second cleaning, the cleaning liquid L2 may be supplied only to the third flow path 253 without being supplied to the first flow path 251, and may flow only inside the sealed space 21A. This allows cleaning of the outer surface 102a.

[0125] (Third cleaning (discharge hole back cleaning)) Next, as shown in FIG. 6, the switching valves SV1 and SV8 are controlled to be OFF, and the first flow path 251 and the fourth flow path 254 are closed.

[0126] In this state, the other switching valves are controlled to supply the cleaning liquid L2 from the cleaning liquid supply unit 23 to the third flow path 253. The cleaning liquid L2 is supplied from the third flow path 253 to the sealed space 21A, and further supplied to the liquid chamber 10A via the discharge hole 102x.

[0127] The waste liquid L3 discharged from the liquid chamber 10A is discharged to the waste liquid tank 241 via the second flow path 252.

[0128] This allows the cleaning liquid L2 to flow from the outside of the liquid chamber 10A toward the inside of the liquid chamber 10A, cleaning the liquid chamber 10A and the sealed space 21 A. The flow of the cleaning liquid L2 causes dirt W2 adhering mainly to the inner surface 102b and the inside of the discharge holes 102x to float up or peel off.

[0129] (4th cleaning (circulation cleaning)) 7, the switching valve SV8 is controlled to be OFF to close the fourth flow path 254. In this state, the other switching valves are controlled to supply the cleaning liquid L2 from the cleaning liquid supply unit 23 to the first flow path 251 and the third flow path 253. As a result, the cleaning liquid L2 is supplied from the first flow path 251 to the liquid chamber 10A, and further supplied from the third flow path 253 to the sealed space 21A.

[0130] Furthermore, the waste liquid L3 discharged from the liquid chamber 10A is discharged to the waste liquid tank 241 via the second flow path 252. This allows the dirt W2 adhering mainly to the inner surface 102b and the inside of the ejection holes 102x to be washed away.

[0131] In addition, a cleaning liquid supply unit having the above-mentioned first supply unit and second supply unit may be used as the cleaning liquid supply unit 23, and the cleaning liquid L2 may be supplied from the first supply unit to the first flow path 251, and the cleaning liquid L2 may be supplied from the second supply unit to the third flow path 253.

[0132] The relatively high-pressure cleaning liquid L2 flows from the third flow path 253 through the sealed space 21A and the discharge hole 102x into the liquid chamber 10A. This prevents the cleaning liquid L2 in the liquid chamber 10A from flowing into the sealed space 21A, and prevents the dirt W2 on the inner surface 102b from flowing into the sealed space 21A.

[0133] In the fourth cleaning, the cleaning liquid L2 may be supplied only to the first flow path 251 without being supplied to the third flow path 253, and may flow only inside the liquid chamber 10A. This allows cleaning of the inner surface 102b.

[0134] 8, the switching valves SV1 and SV4 are controlled to be OFF to close the first flow path 251 and the second flow path 252. In this state, pressurized air is caused to flow from the third flow path 253 toward the fourth flow path 254, thereby discharging the cleaning liquid L2 stored in the third flow path 253, the sealed space 21A, and the fourth flow path 254. The discharged cleaning liquid L2 is discharged, for example, as waste liquid to a waste liquid tank.

[0135] Furthermore, the cleaning liquid L2 inside the liquid chamber 10A is replaced with the raw material liquid L1. The discharged cleaning liquid L2 is discharged, for example, as waste liquid into a waste liquid tank. By this operation, the cleaning of the discharge part 10 is completed.

[0136] According to the droplet forming device 1 configured as above, it is possible to provide a droplet forming device that can clean the nozzles efficiently and effectively.

[0137] In the droplet forming device 1, when the type of raw material liquid to be discharged is changed or when a more advanced cleaning state is required after a long period of operation, the discharge head 100 may be disassembled and cleaned.

[0138] Furthermore, in the droplet forming device 1, four cleaning steps from the first cleaning to the fourth cleaning are performed in stages when cleaning the discharge head 100, but this is not limiting. In the droplet forming device 1, at least one of the four cleaning steps from the first cleaning to the fourth cleaning may be performed independently, and may be combined with another cleaning method such as disassembly cleaning.

[0139] For example, in the droplet forming device 1, the outer surface 102a of the nozzle plate 102 may be cleaned separately, and then the third and fourth cleanings described above may be performed in this order to clean the inside of the liquid chamber 10A.

[0140] Furthermore, in the droplet forming device 1, the above-mentioned first cleaning and second cleaning may be performed in order to clean the outer surface 102a of the nozzle plate 102, and then the inside of the liquid chamber 10A may be cleaned, for example, by disassembling and cleaning the droplet forming device 1.

[0141] Furthermore, in this embodiment, when cleaning the ejection head 100, for example, in the first cleaning, the cleaning liquid L2 is supplied from the first flow path 251 to the liquid chamber 10A, but the cleaning liquid L2 may be supplied to the liquid chamber 10A from the second flow path 252. The supply direction of the cleaning liquid L2 can be appropriately controlled by operating the switching means 26.

[0142] That is, the first flow path 251 and the second flow path 252 can be interchanged for use. At this time, the third flow path 253 and the fourth flow path 254 can also be interchanged for use. Specifically, when the cleaning liquid L2 is supplied from the second flow path 252 to the liquid chamber 10A in the first cleaning, the third flow path 253 and the fourth flow path 254 can be interchanged, and the cleaning liquid L2 supplied to the sealed space 21A via the discharge hole 102x can be discharged from the third flow path 253.

[0143] Similarly, in the second, third, and fourth cleanings, the first flow path 251 and the second flow path 252 can be interchanged, and the third flow path 253 and the fourth flow path 254 can also be interchanged.

[0144] [Second embodiment] 9 to 11 are explanatory diagrams of a droplet forming device and a fine particle manufacturing device according to the second embodiment. In this embodiment, components common to those in the first embodiment are given the same reference numerals, and detailed description thereof will be omitted.

[0145] 《Fine particle manufacturing equipment》 9 is a schematic diagram showing a particle production apparatus 500. The particle production apparatus 500 has a droplet formation device 2, a chamber 510, a collection unit 520, a storage unit 530, and a control unit 550. In the particle production apparatus 500, droplets D discharged from the droplet formation device 2 are solidified to obtain particles.

[0146] The means for solidifying the droplets D in the microparticle production apparatus 500 is not particularly limited as long as it can solidify (solidify) the droplets D, and any known configuration can be appropriately selected. For example, when the droplets D contain a solid raw material and a volatile solvent, the droplets D can be solidified by volatilizing the solvent from the droplets D.

[0147] The microparticles to be produced are not particularly limited, but preferably contain at least one base material and a physiologically active substance having physiological activity, and may contain other materials as necessary. The physiologically active substance may be any substance that has some physiological activity in vivo, but in a preferred embodiment, the physiological activity of the substance changes in response to chemical or physical stimuli such as heating, cooling, shaking, stirring, or pH change.

[0148] The droplet forming device 2 is provided at the top of a cylindrical chamber 510 having an internal space, and discharges droplets D into the internal space of the chamber 510. The configuration of the droplet forming device 2 will be described later.

[0149] The chamber 510 is, for example, a cylindrical member that is open at the top and bottom. The droplet forming device 2 is inserted into the opening at the top of the chamber 510. The diameter of the bottom of the chamber 510 gradually decreases downward. The opening at the bottom of the chamber 510 converges near the central axis.

[0150] The pressure and temperature of the internal space of the chamber 510 are controlled, and the droplets D discharged from the droplet formation device 2 are solidified. In the chamber 510, a downward air current (carrying air current) is formed from above. The droplets D discharged from the droplet formation device 2 are carried downward by gravity and the carrying air current. The angle formed between the flow direction of the carrying air current and the direction in which the droplets D are discharged from the droplet formation device 2 is preferably in the range of 0 to 90 degrees. Here, the "angle formed" is defined as the angle formed by the vectors of the "flow direction of the carrying air current" and the "direction in which the droplets D are discharged from the droplet formation device 2."

[0151] For example, the solvent is removed from the droplets D while they are being transported by the transport airflow, and the droplets D solidify.

[0152] The removal of the solvent can be appropriately controlled by adjusting the temperature of the internal space of the chamber 510, the pressure of the internal space, the temperature of the carrier airflow, the type of gas in the carrier airflow, and the type (vapor pressure) of the solvent.

[0153] The droplets D solidify and produce fine particles, which reach the bottom of the chamber 510 and are then discharged from an opening at the bottom of the chamber 510 .

[0154] The collector 520 collects the fine particles discharged from the lower part of the chamber 510. The collector 520 may have a known configuration such as a cyclone collector or a back filter.

[0155] The storage section 530 stores the particles collected by the collection section 520 .

[0156] The control unit 550 controls the operation of each component of the particle production device 500. The control unit 550 may also function as a control unit for the droplet formation device 2.

[0157] It should be noted that removal of the solvent from the droplets D does not necessarily have to be completed before the droplets D reach the bottom of the chamber 510, as long as coalescence of the droplets D can be suppressed. A configuration may be provided for additionally drying the fine particles collected in the collecting unit 520, which will be described later.

[0158] 《Droplet formation device》 10 and 11 are explanatory diagrams of the droplet forming device 2. Fig. 10 is an overall view, and Fig. 11 is an enlarged view of the vicinity of the ejection head.

[0159] As shown in FIG. 10, the droplet forming device 2 has a discharge unit 60 and a cleaning unit .

[0160] <Discharge part> The ejection unit 60 ejects droplets of the raw material liquid described above. The ejection unit 60 has a liquid chamber 60A that stores the raw material liquid and an ejection hole 602x that communicates with the liquid chamber 60A. The raw material liquid stored in the liquid chamber 60A is ejected through the ejection hole 602x and is formed into a spherical shape in the gas phase due to the surface tension of the raw material liquid.

[0161] The ejection unit 60 has an ejection head 600 having a liquid chamber 60A and an ejection hole 602x, and an ejection unit main body 610 to which the ejection head 600 is connected. The ejection unit 60 has a cylindrical shape, and the ejection head 600 is provided at the bottom end of the cylinder.

[0162] 11, the ejection head 600 has a head main body 601, a nozzle plate 602, and a cover 603. The ejection head 600 can be disassembled into the head main body 601, the nozzle plate 602, and the cover 603. Therefore, when changing the type of raw material liquid to be ejected or when a more advanced cleaning state is required, such as after a long period of operation, the ejection head 600 can be disassembled and cleaned.

[0163] The head main body 601 has a recess 60x that corresponds to the liquid chamber 60A. The recess 60x is formed to extend in the circumferential direction of the head main body 601.

[0164] The nozzle plate 602 has a plurality of ejection holes 602x. The nozzle plate 602 is a curved plate extending in the circumferential direction of the head main body 601, and forms part of the wall surface of the liquid chamber 60A by overlapping with the recess 601x and closing the recess 601x. The plurality of ejection holes 602x are arranged in an array in the extension direction of the nozzle plate 602.

[0165] In the discharge head 600, a plurality of discharge holes 602x are formed and arranged in the circumferential direction along the side surface of the discharge head 600 (discharge section 60).

[0166] The cover 603 presses the nozzle plate 602 against the head body 601, and keeps the contact surfaces between the head body 601 and the nozzle plate 602 liquid-tight.

[0167] The ejection body 610 has a connection part 611 that connects to the ejection head 600 and a cylindrical part 612 that is continuous with the connection part 611 .

[0168] At the connection part 611, the ejection head 600 and the ejection part main body 610 are configured to be detachable at a position 600A. The upper end of the ejection head 600 (the upper end of the head main body 601) has a connection part 601a that connects to the ejection part main body 610.

[0169] The connecting part 601a is formed in a coaxial cylindrical (convex) shape with a diameter smaller than that of the head main body 601, for example. On the other hand, the connecting part 611 of the discharge part main body 610 has a recess at the bottom end that accommodates the connecting part 601a. ​​The connecting part 601a and the connecting part 611 are connected using, for example, a bayonet lock system, making them easily detachable.

[0170] The cylindrical portion 612 has a vibration unit 15 inside that vibrates the raw material liquid stored in the liquid chamber 60A. The vibration unit 15 has an oscillator 151 that generates vibrations and an amplifier 152 that is connected to the oscillator and amplifies the vibrations. The vibration unit 15 is connected to the connection portion 611 at the amplifier 152.

[0171] By providing the vibration unit 15 on the discharge unit main body 610 side, there is no need to detach the wiring connected to the vibration unit 15 when removing the discharge head 600 from the discharge unit main body 610, making the operation of the discharge unit 60 easier. Similarly, there is no need to check the electrical continuity of the wiring connected to the vibration unit 15 when attaching the discharge head 600 to the discharge unit main body 610, making the operation easier.

[0172] Furthermore, since the vibration unit 15 is provided on the discharge unit main body 610 side, the discharge unit 60 does not require a configuration such as a connection terminal for disconnecting and reconnecting the wiring connected to the vibration unit 15. Therefore, problems that can arise from employing such a configuration, such as poor contact caused by the connection terminal becoming dirty and causing the vibration unit 15 to not work, do not occur.

[0173] Furthermore, since the vibration unit 15 is provided on the ejection unit main body 610 side, when disassembling and cleaning the ejection head 600, it is possible to carry out processes that may deteriorate the electrical wiring, such as ultrasonic cleaning while the ejection head 600 is immersed in a cleaning liquid, or sterilization treatment using an autoclave or boiling.

[0174] The vibrator 151 can have the same configuration as the vibrating section used in the first embodiment.

[0175] A known horn-type vibration amplifier can be used as the amplifier means 152. Examples of the horn-type vibration amplifier include a step type, an exponential type, and a conical type.

[0176] <Cleaning section> As shown in FIG. 10, the cleaning unit 70 includes a sealed space forming means 71 and a moving means 75.

[0177] The sealed space forming means 71 is a cylindrical member that covers the side surface of the ejection head 600. The sealed space forming means 71 is capable of forming a liquid-tight sealed space 71A that communicates with the liquid chamber 60A via the ejection holes 602x outside the ejection part 60. Note that in Figure 10, the ejection head 600 and the sealed space forming means 71 are shown separated from each other to make each component easier to see.

[0178] More specifically, the sealed space forming means 71 has a recess 71x facing the discharge head 600, and contacts the discharge head 600 by covering the discharge holes 602x from the side of the discharge head 600. The recess 71x is continuous in the circumferential direction on the inner surface of the sealed space forming means 71. The space surrounded by the recess 71x and the side of the discharge head 600 is the sealed space 71A.

[0179] The sealed space forming means 71 can be moved up and down by a moving means 75 provided on the upper part of the sealed space forming means 71. Fig. 9 shows the sealed space forming means 71 in a retracted state in the upper part, and Fig. 10 shows the sealed space forming means 71 in a state where it has descended and covers the side surface of the discharge head 600 to form a sealed space 71A.

[0180] In this embodiment, the sealed space forming means 71 is moved up and down, but the discharge section 60 may be configured to move up and down, and the relative positions of the discharge section 60 and the sealed space forming means 71 may be changed.

[0181] The cleaning unit 70 also has the flow unit shown in the first embodiment. The flow unit has a cleaning liquid supply unit 23, a waste liquid discharge unit 24, a first flow path 251, a second flow path 252, a third flow path 253, a fourth flow path 254, and a switching means 26.

[0182] The first flow path 251 and the second flow path 252 are connected to the liquid chamber 60A. The first flow path 251 and the second flow path 252 are provided to extend inside the cylindrical portion 612, and are connected to the cleaning liquid supply part 23 and the waste liquid discharge part 24 via the switching means 26, respectively.

[0183] The third flow path 253 and the fourth flow path 254 are connected to the sealed space 71 A. The third flow path 253 and the fourth flow path 254 are provided to extend inside the cylindrical portion 612, and are connected to the cleaning liquid supply part 23 and the waste liquid discharge part 24 via the switching means 26, respectively.

[0184] The first flow path 251, the second flow path 252, the third flow path 253, and the fourth flow path 254 are separated midway along their respective paths when the discharge head 600 is removed from the discharge-part main body 610. Furthermore, by connecting the discharge head 600 to the discharge-part main body 610, the first flow path 251, the second flow path 252, the third flow path 253, and the fourth flow path 254 connect the respective flow paths in the discharge head 600 to the respective flow paths in the discharge-part main body 610.

[0185] Even in a droplet forming device 2 configured in this manner, when the raw material liquid is repeatedly ejected from the ejection hole 602x, some of the solid content contained in the raw material liquid L1 may precipitate on the outer wall of the liquid chamber 60A (the outer surface of the nozzle plate 602) and the inner wall of the liquid chamber 60A (the inner surface of the nozzle plate 102), causing dirt to adhere to them.

[0186] In the droplet forming device 2, the discharge part 60 can be easily cleaned by using the cleaning part 70 to deal with such stains. The method for cleaning the discharge part 60 using the cleaning part 70 is the same as the method for cleaning the discharge part 10 using the cleaning part 20 of the first embodiment.

[0187] According to the droplet forming device 2 configured as above, it is possible to provide a droplet forming device that can clean the nozzles efficiently and effectively.

[0188] Furthermore, the particle production apparatus 500 configured as described above is equipped with the droplet formation device 2 and can produce high-quality particles.

[0189] While the preferred embodiments of the present invention have been described above with reference to the accompanying drawings, the present invention is not limited to these examples. The shapes and combinations of the components shown in the above examples are merely examples, and various modifications can be made based on design requirements, etc., without departing from the spirit of the present invention. [Example]

[0190] The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0191] In each of the examples and comparative examples, the following raw material solutions were used for evaluation.

[0192] Metformin hydrochloride (manufactured by Tokyo Chemical Industry Co., Ltd.) was pulverized in a ball mill until the volume average particle size became 1.5 μm.

[0193] Eight parts by mass of pulverized metformin hydrochloride, 12 parts by mass of lactic acid-glycolic acid copolymer (product name PLGA-7510, manufactured by Wako Pure Chemical Industries, Ltd.), and 80 parts by mass of acetone (manufactured by Wako Pure Chemical Industries, Ltd.) were mixed and stirred at 1000 rpm for 1 hour using a stirring device (device name: Magnetic Stirrer, manufactured by AS ONE Corporation) to prepare a raw material solution.

[0194] Since metformin hydrochloride is insoluble in acetone, the obtained raw material liquid was a dispersion of metformin hydrochloride.

[0195] Example 1 The droplet forming device and the fine particle producing device shown in the second embodiment were prepared. The capacity of the liquid chamber was 150 mm 3 , the capacity of the enclosed space is 1000mm 3 It was.

[0196] The droplet forming device according to Example 1 was evaluated in the following manner.

[0197] ((1) Pre-cleaning discharge) The nozzle plate was fabricated from a nickel plate measuring 42.5 mm in length, 6.8 mm in width, and 20 μm in thickness. Multiple ejection holes with a diameter of 35 μm were formed in the nickel plate by electroforming. The distance between the ejection holes was set to 200 μm.

[0198] The liquid source was poured into the liquid chamber, and while applying a 70 kHz vibration from the vibration unit, a pressure of 0.1 MPa was applied to the liquid source in the liquid chamber through the discharge holes, thereby discharging droplets. The pressure applied to the discharge holes was measured using a pressure measuring device (Keyence Corporation, AP-13S) installed in a position relatively close to the discharge holes in the first flow path. The pressure measuring device was installed as close to the discharge holes as possible in the first flow path.

[0199] The chamber was cylindrical with a diameter of 800 mm and a height of 1540 mm. The droplet generator was inserted into the chamber from the top end, and the discharge head was located 50 to 100 mm below the top end of the chamber. A 1000 m³ flow was used as a transport airflow from the periphery of the droplet generator toward the bottom of the chamber. 3 Room temperature air was flowed at 1 / min.

[0200] The raw material liquid was discharged from the droplet forming device, and the fine particles solidified in the chamber were collected by a cyclone collector installed at the bottom of the chamber, to obtain particles before washing.

[0201] ((2) Cleaning) The ejection head was cleaned once every 20 minutes using the cleaning unit. Cleaning was performed according to the following procedure.

[0202] (Cleaning the ejection head) During cleaning, first, the droplet discharge from the droplet generating device was stopped, and then the side of the discharge head was covered with the sealed space forming means to form a sealed space. Acetone was used as the cleaning liquid.

[0203] First, the cleaning liquid was supplied from the first flow path to the liquid chamber, then flowed from the liquid chamber to the sealed space via the discharge hole, and then discharged from the fourth flow path. The pressure of the cleaning liquid supplied from the first flow path was 0.15 MPa, and the cleaning liquid delivery time was 15 seconds (first cleaning, discharge hole cleaning).

[0204] Next, the cleaning liquid was supplied to the sealed space from the third flow path and discharged from the fourth flow path. The pressure of the cleaning liquid supplied from the third flow path was 0.15 MPa, and the cleaning liquid flow time was 5 seconds (second cleaning: external surface cleaning). Approximately 50 to 100 mL of the cleaning liquid flowed during the liquid flow time.

[0205] Next, the cleaning liquid was supplied from the third flow path to the sealed space, flowed from the sealed space to the liquid chamber through the discharge hole, and discharged from the second flow path. The pressure of the cleaning liquid supplied from the third flow path was 0.15 MPa, and the cleaning liquid delivery time was 15 seconds (third cleaning, discharge hole backwashing).

[0206] Next, the cleaning liquid was supplied to the sealed space from the first flow path and discharged from the second flow path. The pressure of the cleaning liquid supplied from the first flow path was 0.15 MPa, and the cleaning liquid flow time was 15 seconds (fourth cleaning, circulating cleaning). Approximately 50 to 100 mL of the cleaning liquid flowed during the liquid flow time.

[0207] Next, the cleaning liquid in the liquid chamber was replaced with the raw material liquid, and the closed space forming means was retracted to complete the cleaning.

[0208] ((3) Discharge hole condition after cleaning) After cleaning, the state of the ejection holes (nozzles) of the ejection head was evaluated by the method described below.

[0209] ((4) Discharge after cleaning) After washing, the raw material liquid was discharged under the same conditions as in ((1) Discharge before washing) to obtain washed particles of Example 1. In addition, the recovery rate of the discharge holes (recovery rate after discharge) was evaluated by the method described below.

[0210] (Examples 2 to 6, Comparative Example) Examples 2 to 6 and a comparative example were carried out in the same manner as in Example 1, except that the above conditions (cleaning of the ejection head) were changed under the conditions shown in Table 1. In the comparative example, the same equipment as in Examples 1 to 6 was used, but not all cleaning was performed, and therefore the results of the comparative example are thought to be the same as those of a configuration that does not have a cleaning unit.

[0211] (Measurement of average particle size distribution) The average particle size distribution of the particles obtained in Examples 1 to 6 and Comparative Example ((4) Discharge after washing) was measured by the following method.

[0212] -Particle size measurement method- The measurement method using a flow particle image analyzer (FPIA-3000) manufactured by Sysmex Corporation is described below.

[0213] The measurements were carried out according to the following steps (1) to (3). (1) The water used for measurement is passed through a filter to remove fine particles. -3 cm 3 The water obtained contained 20 or fewer particles in the measurement range (circular equivalent diameter: 0.60 μm or more and less than 159.21 μm). (2) Add a few drops of a nonionic surfactant (preferably Contaminon N manufactured by Wako Pure Chemical Industries, Ltd.) to 10 ml of the water, add 5 mg of the measurement sample, and disperse the mixture in an ultrasonic disperser UH-50 manufactured by STM Co., Ltd. at 20 kHz, 50 W / 10 cm. 3 Dispersion treatment was carried out for 1 minute under the conditions. (3) Next, disperse the sample for a total of 5 minutes until the particle concentration of the sample reaches 4,000 to 8,000 particles / 10 -3 cm 3 Using a sample dispersion (targeting particles within the measurement equivalent circle diameter range), the particle size distribution of particles having an equivalent circle diameter of 0.60 μm or more and less than 159.21 μm was measured.

[0214] The sample dispersion was passed through the flow channel (which extended in the direction of flow) of a flat, transparent flow cell (approximately 200 μm thick). To form a light path that crossed the thickness of the flow cell, a strobe and a CCD camera were attached to the flow cell, positioned on opposite sides of each other. While the sample dispersion was flowing, the strobe light was irradiated at 1 / 30 second intervals to obtain images of particles flowing through the flow cell. As a result, each particle was captured as a two-dimensional image with a certain range parallel to the flow cell. From the area of ​​each two-dimensional image of each particle, the diameter of a circle with the same area was calculated as the equivalent circle diameter. In about one minute, the equivalent circular diameters of over 1,200 particles could be measured, and the number based on the equivalent circular diameter distribution and the percentage of particles with a specified equivalent circular diameter (number %) were measured. The results (frequency % and cumulative %) were obtained by dividing the range of 0.06-400 μm into 226 channels (30 channels per octave). In the actual measurements, particles with equivalent circular diameters between 0.60 μm and 159.21 μm were measured.

[0215] The volume average particle size (Dv) and number average particle size (Dn) were determined, and Dv / Dn was calculated as the average particle size distribution.

[0216] The evaluation results are shown in Table 1. Each column in Table 1 lists a four-level evaluation of A, B, C, and D, with A, B, and C being evaluated as good and D being evaluated as poor. The evaluation criteria listed in Table 1 are also shown in Table 2.

[0217] Each evaluation listed in Table 1 was performed by photographing the discharge hole surface with a camera after cleaning under each condition and visually inspecting the image after enlarging it. Specifically, an image of an area of ​​approximately 2 mm x 1.5 mm on the discharge hole surface was photographed, and the photographed image was enlarged to fill the entire screen of a 19-inch display (screen aspect ratio 4:3) for inspection. From the ratio of the diagonal length of the photographed image and the display (2.5 mm:482.6 mm), the magnification was calculated to be 193 times. The definitions of each evaluation are as follows:

[0218] (Discharge hole condition after cleaning) In ((3) Discharge hole condition after cleaning), the number of discharge holes with remaining dirt around them was counted in the captured image. When "dirt" remained, solid matter thought to be metformin hydrochloride was observed to block the nozzle holes or adhere to the nozzle surface. The ratio of the number of discharge holes with remaining dirt (B) to the total number of discharge holes (A) was calculated as a percentage (B / A x 100%).

[0219] (Recovery rate after discharge) In ((4) Discharge after cleaning), the raw material liquid was discharged from the discharge holes after cleaning, and the ratio of the number of discharge holes that discharged normally (C) to the total number of discharge holes (A) was calculated as a percentage (C / A x 100%).

[0220] "Normal ejection" means that, in the operation of ejecting one droplet, the droplet is ejected from the ejection hole in a direction perpendicular to the nozzle plate. Therefore, when attempting to eject a single droplet, if any of the following conditions occur, it is evaluated as "abnormal ejection." (i) No ejection occurs, (ii) The raw material liquid drips from the ejection hole along the surface of the nozzle plate, (iii) The droplet is ejected at a curved angle rather than perpendicular to the nozzle plate, or (iv) Multiple droplets are ejected from the ejection hole.

[0221] (Average particle size distribution) The average particle size distribution of the particles obtained in ((4) Discharge after washing) was measured.

[0222] (Effect after washing) The lowest evaluation result is shown among the three evaluation items: discharge hole condition after cleaning, recovery rate after discharge, and average particle size distribution.

[0223] [Table 1]

[0224] [Table 2]

[0225] In all of Examples 1 to 6, the effect of cleaning the discharge head using the sealed space forming part was confirmed, and the condition of the discharge holes after cleaning was good. In addition, it was found that the particle size distribution of the formed particles was narrow and the variation in particle size was small.

[0226] In contrast, in the comparative example in which cleaning using the sealed space forming part was not performed, a large amount of dirt adhered to the discharge hole and the vicinity of the discharge hole as the device was used. In addition, in the comparative example, the particle size distribution of the particles was also affected by the adhesion of dirt, resulting in a larger variation compared to Examples 1 to 6.

[0227] The above results confirmed that the present invention is useful.

[0228] The present invention includes the following aspects.

[0229] [1] A droplet forming device comprising a liquid chamber, an ejection hole that ejects a raw material liquid in the liquid chamber as droplets, a sealed space forming means, and at least two flow paths, wherein the sealed space forming means is capable of forming a sealed space that communicates with the liquid chamber via the ejection hole on the opposite side of the liquid chamber from the ejection hole, and the at least two flow paths are connected to each other via the sealed space.

[0230] [2] The droplet forming device according to [1], wherein a cleaning liquid is caused to flow through the liquid chamber and the sealed space, thereby cleaning the inside of the liquid chamber, the discharge hole, and the sealed space.

[0231] [3] The droplet forming device described in [2] further comprises a cleaning liquid supply unit that supplies the cleaning liquid, and a waste liquid discharge unit that discharges waste liquid generated by cleaning the liquid chamber, the discharge hole, and the inside of the sealed space, wherein the at least two flow paths include a first flow path and a second flow path that are connected to the liquid chamber and are openable and closable, and a third flow path and a fourth flow path that are openable and closable at positions that can be connected to the sealed space, wherein the first flow path and the second flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit, and the third flow path and the fourth flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit.

[0232] [4] A droplet forming device according to [3], which has a control unit that controls at least the cleaning liquid supply unit and the waste liquid discharge unit, wherein the control unit performs a first cleaning by closing the second flow path and the third flow path, supplying the cleaning liquid from the first flow path through the liquid chamber to the sealed space, and discharging the waste liquid in the sealed space from the fourth flow path.

[0233] [5] A droplet forming device according to [3] or [4], which has a control unit that controls at least the cleaning liquid supply unit and the waste liquid discharge unit, wherein the control unit performs a second cleaning by closing the second flow path, supplying the cleaning liquid to the sealed space from one of the third flow path and the fourth flow path, and discharging the waste liquid in the sealed space from the other of the third flow path and the fourth flow path.

[0234] [6] The droplet forming device described in [5], wherein the cleaning liquid supply unit has a first supply unit that supplies the cleaning liquid and a second supply unit that supplies the cleaning liquid at a higher pressure than the first supply unit, and in the second cleaning, the cleaning liquid is supplied from the second supply unit to the first flow path, and the cleaning liquid is supplied from the first supply unit to one of the third flow path and the fourth flow path.

[0235] [7] A droplet forming device described in any one of [3] to [6], which has a control unit that controls at least the cleaning liquid supply unit and the waste liquid discharge unit, and the control unit performs a third cleaning by closing the first flow path and the fourth flow path, supplying the cleaning liquid from the third flow path to the liquid chamber through the sealed space, and discharging the waste liquid from the liquid chamber through the second flow path.

[0236] [8] A droplet forming device described in any one of [3] to [7], which has a control unit that controls at least the cleaning liquid supply unit and the waste liquid discharge unit, and the control unit performs a fourth cleaning by closing the fourth flow path, supplying the cleaning liquid to the liquid chamber from one of the first flow path and the second flow path, and discharging the waste liquid in the liquid chamber from the other of the first flow path and the second flow path.

[0237] [9] The droplet forming device described in [8], wherein the cleaning liquid supply unit has a first supply unit that supplies the cleaning liquid and a second supply unit that supplies the cleaning liquid at a higher pressure than the first supply unit, and in the fourth cleaning, the cleaning liquid is supplied from the second supply unit to the third flow path, and the cleaning liquid is supplied from the first supply unit to one of the first flow path and the second flow path.

[0238]

[10] A droplet forming device described in any one of [3] to [9], wherein the first flow path is switchably connected to the cleaning liquid supply unit and a raw material liquid supply unit that supplies the raw material liquid.

[0239]

[11] A droplet forming device according to any one of [1] to

[10] , comprising an ejection head having the liquid chamber and the ejection hole, and an ejection unit main body to which the ejection head is connected, wherein the ejection head and the ejection unit main body are configured to be detachable.

[0240]

[12] The droplet forming device described in

[11] , wherein the ejection head has a head body in which the liquid chamber is provided and a nozzle plate that forms part of the wall surface of the liquid chamber and has the ejection holes, and the ejection head can be disassembled into the head body and the nozzle plate.

[0241]

[13] The droplet forming device according to

[11] or

[12] , wherein the ejection unit main body has a vibration unit that applies vibration to the raw material liquid stored in the liquid chamber.

[0242]

[14] The droplet forming device according to

[13] , wherein the vibration unit has a vibrator that generates vibrations and an amplifier that is connected to the vibrator and amplifies the vibrations.

[0243]

[15] A fine particle manufacturing apparatus comprising the droplet forming device according to any one of [1] to

[14] and solidifying means for solidifying droplets discharged from the droplet forming device.

[0244] The present invention also includes the following aspects.

[0245] [1-1] A discharge head having a liquid chamber, a discharge hole that discharges the raw material liquid in the liquid chamber as droplets, and at least two flow paths; A sealed space forming means; a cleaning liquid supply unit that supplies the cleaning liquid; a waste liquid discharge section that discharges waste liquid generated by cleaning the interior of the liquid chamber, the discharge hole, and the sealed space; a control unit that controls at least the cleaning liquid supply unit and the waste liquid discharge unit, the sealed space forming means is capable of forming a sealed space on the opposite side of the ejection hole from the liquid chamber, the sealed space communicating with the liquid chamber via the ejection hole; the at least two flow paths are a first flow path and a second flow path connected to the liquid chamber and provided so as to be openable and closable; a third flow path and a fourth flow path that are openable and closable and are provided at positions that are connectable to the sealed space, the at least two flow paths are in communication with each other via the sealed space, the first flow path and the second flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit, the third flow path and the fourth flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit, a cleaning liquid is caused to flow through the liquid chamber and the sealed space, thereby cleaning the inside of the liquid chamber, the discharge hole, and the sealed space; a first cleaning in which the control unit closes the second flow path and the third flow path, supplies the cleaning liquid from the first flow path through the liquid chamber to the sealed space, and discharges the waste liquid in the sealed space from the fourth flow path; a second cleaning step of closing the second flow path, supplying the cleaning liquid to the sealed space from one of the third flow path and the fourth flow path, and discharging the waste liquid from the sealed space from the other of the third flow path and the fourth flow path.

[0246] [1-2] The cleaning liquid supply unit includes a first supply unit that supplies the cleaning liquid; a second supply unit that supplies the cleaning liquid at a higher pressure than the first supply unit; The droplet forming device described in [1-1], wherein in the second cleaning, the cleaning liquid is supplied from the second supply unit to the first flow path, and the cleaning liquid is supplied from the first supply unit to one of the third flow path and the fourth flow path.

[0247] [1-3] The droplet forming device according to [1-2], wherein the first flow path is switchably connected to the cleaning liquid supply unit and a raw material liquid supply unit that supplies the raw material liquid.

[0248] [2-1] A discharge head having a liquid chamber, a discharge hole for discharging the raw material liquid in the liquid chamber as droplets, and at least two flow paths; A sealed space forming means; a cleaning liquid supply unit that supplies the cleaning liquid; a waste liquid discharge section that discharges waste liquid generated by cleaning the interior of the liquid chamber, the discharge hole, and the sealed space; a control unit that controls at least the cleaning liquid supply unit and the waste liquid discharge unit, the sealed space forming means is capable of forming a sealed space on the opposite side of the ejection hole from the liquid chamber, the sealed space communicating with the liquid chamber via the ejection hole; the at least two flow paths are a first flow path and a second flow path connected to the liquid chamber and provided so as to be openable and closable; a third flow path and a fourth flow path that are openable and closable and are provided at positions that are connectable to the sealed space, the at least two flow paths are in communication with each other via the sealed space, the first flow path and the second flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit, the third flow path and the fourth flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit, a cleaning liquid is caused to flow through the liquid chamber and the sealed space, thereby cleaning the inside of the liquid chamber, the discharge hole, and the sealed space; a third cleaning in which the control unit closes the first flow path and the fourth flow path, supplies the cleaning liquid from the third flow path through the sealed space to the liquid chamber, and discharges the waste liquid from the liquid chamber through the second flow path; a fourth cleaning in which the fourth flow path is closed, the cleaning liquid is supplied to the liquid chamber from one of the first flow path and the second flow path, and the waste liquid in the liquid chamber is discharged from the other of the first flow path and the second flow path.

[0249] [2-2] The cleaning liquid supply unit includes a first supply unit that supplies the cleaning liquid; a second supply unit that supplies the cleaning liquid at a higher pressure than the first supply unit; The droplet forming device described in [2-1], wherein in the fourth cleaning, the cleaning liquid is supplied from the second supply unit to the third flow path, and the cleaning liquid is supplied from the first supply unit to one of the first flow path and the second flow path.

[0250] [2-3] The droplet forming device according to [2-2], wherein the first flow path is switchably connected to the cleaning liquid supply unit and a raw material liquid supply unit that supplies the raw material liquid.

[0251] [3-1] A discharge head having a liquid chamber, a discharge hole for discharging the raw material liquid in the liquid chamber as droplets, and at least two flow paths; A sealed space forming means; a cleaning liquid supply unit that supplies the cleaning liquid; a waste liquid discharge section that discharges waste liquid generated by cleaning the interior of the liquid chamber, the discharge hole, and the sealed space; a control unit that controls at least the cleaning liquid supply unit and the waste liquid discharge unit, the sealed space forming means is capable of forming a sealed space on the opposite side of the ejection hole from the liquid chamber, the sealed space communicating with the liquid chamber via the ejection hole; the at least two flow paths are a first flow path and a second flow path connected to the liquid chamber and provided so as to be openable and closable; a third flow path and a fourth flow path that are openable and closable and are provided at positions that are connectable to the sealed space, the at least two flow paths are in communication with each other via the sealed space, the first flow path and the second flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit, the third flow path and the fourth flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit, a cleaning liquid is caused to flow through the liquid chamber and the sealed space, thereby cleaning the inside of the liquid chamber, the discharge hole, and the sealed space; a first cleaning in which the control unit closes the second flow path and the third flow path, supplies the cleaning liquid from the first flow path through the liquid chamber to the sealed space, and discharges the waste liquid in the sealed space from the fourth flow path; a second cleaning step of closing the second flow path, supplying the cleaning liquid to the sealed space from one of the third flow path and the fourth flow path, and discharging the waste liquid in the sealed space from the other of the third flow path and the fourth flow path; a third cleaning in which the first flow path and the fourth flow path are closed, the cleaning liquid is supplied from the third flow path through the sealed space to the liquid chamber, and the waste liquid in the liquid chamber is discharged from the second flow path; a fourth cleaning in which the fourth flow path is closed, the cleaning liquid is supplied to the liquid chamber from one of the first flow path and the second flow path, and the waste liquid in the liquid chamber is discharged from the other of the first flow path and the second flow path. [Explanation of symbols]

[0252] 1, 2... droplet forming device, 10, 60... discharge section, 10A, 60A... liquid chamber, 15... vibration section, 20, 70... cleaning section, 21, 71... sealed space forming means, 21A, 71A... sealed space, 22... flow section, 23... cleaning liquid supply section, 24... waste liquid discharge section, 50, 550... control section, 100, 600... discharge head, 101, 601... head body, 102, 60 2...Nozzle plate, 102x, 602x...Discharge holes, 110, 610...Discharge unit main body, 151...Vibrator, 152...Amplification means, 191...Material liquid tank, 231...Cleaning liquid tank, 251...First flow path, 252...Second flow path, 253...Third flow path, 254...Fourth flow path, 500...Particle manufacturing device, D...Droplets, L1...Material liquid, L2...Cleaning liquid, L3...Waste liquid [Prior art documents] [Patent documents]

[0253] [Patent Document 1] Japanese Patent Application Laid-Open No. 2015-027657

Claims

1. A liquid chamber; a discharge hole for discharging the raw material liquid in the liquid chamber as droplets; A sealed space forming means; a first flow path, a second flow path, a third flow path, and a fourth flow path; the sealed space forming means is capable of forming a sealed space on the opposite side of the ejection hole from the liquid chamber, the sealed space communicating with the liquid chamber via the ejection hole; the first flow path and the second flow path are connected to the liquid chamber and are openable and closable; the third flow path and the fourth flow path are openably and closably provided at positions connectable to the sealed space on the same side of the ejection hole as the liquid chamber, The droplet forming device, wherein the first flow path and the second flow path are respectively connected to the third flow path and the fourth flow path via the sealed space and the liquid chamber.

2. The droplet forming device according to claim 1, wherein a cleaning liquid is caused to flow through the liquid chamber and the sealed space, thereby cleaning the inside of the liquid chamber, the ejection hole, and the sealed space.

3. a cleaning liquid supply unit that supplies the cleaning liquid; a waste liquid discharge section that discharges waste liquid generated by cleaning the liquid chamber, the discharge hole, and the inside of the sealed space, the first flow path and the second flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit, The droplet forming device according to claim 2 , wherein the third flow path and the fourth flow path are connected to the cleaning liquid supply unit and the waste liquid discharge unit.

4. a control unit for controlling at least the cleaning liquid supply unit and the waste liquid discharge unit; 4. The droplet forming device according to claim 3, wherein the control unit performs a first cleaning in which the second flow path and the third flow path are closed, the cleaning liquid is supplied from the first flow path through the liquid chamber to the sealed space, and the waste liquid in the sealed space is discharged from the fourth flow path.

5. a control unit for controlling at least the cleaning liquid supply unit and the waste liquid discharge unit; The droplet forming device according to claim 3 or 4, wherein the control unit performs a second cleaning by closing the second flow path, supplying the cleaning liquid to the sealed space from one of the third flow path and the fourth flow path, and discharging the waste liquid in the sealed space from the other of the third flow path and the fourth flow path.

6. The cleaning liquid supply unit includes a first supply unit that supplies the cleaning liquid; a second supply unit that supplies the cleaning liquid at a higher pressure than the first supply unit, The droplet forming device according to claim 5 , wherein in the second cleaning, the cleaning liquid is supplied from the second supply unit to the first flow path, and the cleaning liquid is supplied from the first supply unit to one of the third flow path and the fourth flow path.

7. a control unit for controlling at least the cleaning liquid supply unit and the waste liquid discharge unit; The droplet forming device according to any one of claims 3 to 6, wherein the control unit performs a third cleaning by closing the first flow path and the fourth flow path, supplying the cleaning liquid to the liquid chamber from the third flow path through the sealed space, and discharging the waste liquid from the liquid chamber from the second flow path.

8. a control unit for controlling at least the cleaning liquid supply unit and the waste liquid discharge unit; 8. The droplet forming device according to claim 3, wherein the control unit performs a fourth cleaning by closing the fourth flow path, supplying the cleaning liquid to the liquid chamber from one of the first flow path and the second flow path, and discharging the waste liquid from the liquid chamber from the other of the first flow path and the second flow path.

9. The cleaning liquid supply unit includes a first supply unit that supplies the cleaning liquid; a second supply unit that supplies the cleaning liquid at a higher pressure than the first supply unit, The droplet forming device according to claim 8 , wherein in the fourth cleaning, the cleaning liquid is supplied from the second supply unit to the third flow path, and the cleaning liquid is supplied from the first supply unit to one of the first flow path and the second flow path.

10. The droplet forming device according to claim 3 , wherein the first flow path is switchably connected to the cleaning liquid supply unit and a raw material liquid supply unit that supplies the raw material liquid.

11. a discharge head having the liquid chamber and the discharge hole; a discharge unit main body to which the discharge head is connected, The droplet forming device according to claim 1 , wherein the ejection head and the ejection unit main body are configured to be detachable.

12. The ejection head includes a head body provided with the liquid chamber; a nozzle plate that forms a part of the wall surface of the liquid chamber and has the ejection holes; The droplet forming device according to claim 11 , wherein the ejection head is separable into the head body and the nozzle plate.

13. The droplet forming device according to claim 11 or 12, wherein the ejection unit main body has a vibration unit that applies vibration to the raw material liquid stored in the liquid chamber.

14. The vibration unit includes a vibrator that generates vibrations; The droplet forming device according to claim 13, further comprising: an amplifier connected to the vibrator for amplifying the vibration.

15. A droplet forming device according to any one of claims 1 to 14; and solidifying means for solidifying the droplets discharged from the droplet forming device.

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