Droplet forming device and fine particle manufacturing device

Abstract

To provide: a droplet forming apparatus less susceptible to influence due to dirt attached to surroundings of a nozzle; and a fine particle manufacturing apparatus which includes the droplet forming apparatus and makes it possible to stably manufacture high-quality fine particles.SOLUTION: A droplet forming apparatus includes a discharge head to discharge droplets of a raw material liquid. The discharge head includes a plurality of ejection pores. These ejection pores are formed on a lateral surface of the discharge head. These ejection pores are individually disposed at positions not overlapped with an imaginary range where the raw material liquid seems to drip and spread from the ejection pores in the lateral surface.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] The present invention relates to a droplet forming device and a fine particle manufacturing device. [Background technology]

[0002] Fine particles with a narrow particle size distribution are used for various purposes, such as toner fine particles for electrophotography, spacer particles for liquid crystal panels, and carriers for biologically active substances such as pharmaceutical compounds. Among these, a manufacturing device that ejects liquid toner material as droplets and granulates them into fine particles of a desired particle size is known as a device for manufacturing toner fine particles (see, for example, Patent Document 1). In the manufacturing device described in Patent Document 1, a raw material liquid containing fine particle material is ejected as droplets from a nozzle, and the solvent is removed from the droplets to manufacture fine particles having a desired particle size distribution. Summary of the Invention [Problem to be solved by the invention]

[0003] The above-mentioned Patent Document 1 shows an example of a configuration in which multiple nozzles are arranged vertically (in the direction of gravity) to eject material. By arranging multiple nozzles in this way, it is expected that productivity will improve.

[0004] On the other hand, it is known that when the raw material liquid is discharged from the nozzle, dirt caused by fine particles of the material adheres to the area around the nozzle. Since such dirt affects the size of the droplets discharged from the nozzle and production efficiency, measures to prevent this are required.

[0005] The present invention has been made in view of the above circumstances, and has an object to provide a droplet forming device that is not easily affected by dirt adhering to the periphery of the nozzle. Another object of the present invention is to provide a particle manufacturing device that includes the droplet forming device and enables stable production of high-quality particles. [Means for solving the problem]

[0006] The inventors thought that if, when the raw material liquid is ejected from the nozzle, the raw material liquid adheres to the area around the nozzle and causes dirt, the effects of dirt can be suppressed by placing the nozzle in a position where dirt is less likely to occur, and completed the present invention.

[0007] That is, in order to solve the above-mentioned problems, one aspect of the present invention provides a droplet forming device having an ejection head that ejects droplets of a raw material liquid, the ejection head having a plurality of ejection holes, the plurality of ejection holes being formed on a side surface of the ejection head, and each of the plurality of ejection holes being provided at a position on the side surface that does not overlap with a virtual range in which the raw material liquid is assumed to drip and spread from the ejection holes. Effect of the Invention

[0008] According to the present invention, it is possible to provide a droplet forming device that is not easily affected by dirt adhering to the periphery of the nozzle. It is also possible to provide a microparticle manufacturing device that includes the droplet forming device and enables stable production of high-quality microparticles. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a schematic diagram showing a fine particle production apparatus 500. As shown in FIG. [Diagram 2] FIG. 2 is a partial enlarged view of the discharge section. [Diagram 3] FIG. 3 is an enlarged view illustrating the arrangement of the discharge holes 102x. [Figure 4] FIG. 4 is a schematic diagram showing the state of the periphery of the discharge hole 102x on the side surface 100a. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Hereinafter, a droplet forming device and a microparticle manufacturing device according to the present embodiment will be described with reference to Figures 1 to 4. In addition, in all the following figures, the dimensions and ratios of each component are appropriately changed in order to make the drawings easier to see.

[0011] In the following description, an xyz Cartesian coordinate system is set, and the positional relationship of each member is described with reference to this xyz Cartesian coordinate system. Here, a specific direction in a horizontal plane is defined as the x-axis direction, a direction perpendicular to the x-axis direction in the horizontal plane is defined as the y-axis direction, and a direction perpendicular to both the x-axis direction and the y-axis direction (i.e., the vertical direction) is defined as the z-axis direction.

[0012] In the following explanation, the +z direction may be referred to as "upper" or "upper side", and the -z direction may be referred to as "lower" or "lower side". "Upper side" refers to the +z side of a structure, "upper part" refers to the +z side part of a structure, "lower side" refers to the -z side of a structure, and "lower part" refers to the -z side part of a structure.

[0013] 1 is a schematic diagram showing a microparticle production apparatus 500. The microparticle production apparatus 500 includes a droplet forming device 1, a chamber 510, a collector 520, a reservoir 530, and a controller 550. In the microparticle production apparatus 500, droplets D discharged from the droplet forming device 1 are solidified to obtain microparticles.

[0014] 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 a 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.

[0015] The microparticles to be produced are not particularly limited, but preferably contain at least one kind of substrate 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 the living body, 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.

[0016] The droplet forming device 1 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 1 will be described later.

[0017] The chamber 510 is, for example, a cylindrical member with an opening at the top and bottom. The droplet forming device 1 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.

[0018] The pressure and temperature of the internal space of the chamber 510 are controlled, and the droplets D discharged from the droplet forming device 1 are solidified. In the chamber 510, a downward air current (carrying air current) is formed from above. The droplets D discharged from the droplet forming device 1 are carried downward by gravity and the carrying air current. It is preferable that the flow direction of the carrying air current is approximately perpendicular to the direction in which the droplets D are discharged from the droplet forming device 1.

[0019] For example, the solvent is removed from the droplets D while they are being transported by the transport air current, and the droplets D solidify.

[0020] 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.

[0021] The fine particles generated by solidifying the droplets D reach the bottom of the chamber 510 and are then discharged from an opening at the bottom of the chamber 510 .

[0022] The collector 520 collects the fine particles discharged from the lower part of the chamber 510. The collector 520 may have a known structure such as a cyclone collector or a back filter.

[0023] The storage section 530 stores the particles collected by the collection section 520 .

[0024] The control unit 550 controls the operation of each component of the fine particle production apparatus 500. The control unit 550 may also function as the control unit of the droplet formation device 1.

[0025] In addition, the removal of the solvent from the droplets D does not necessarily have to be completed before the droplets D reach the lower part of the chamber 510, so long as the droplets D can be prevented from coalescing with each other. A configuration for additionally drying the fine particles collected by the collecting unit 520 described later may be provided.

[0026] 《Droplet formation device》 The droplet forming device 1 includes a discharge unit 10 and a raw material liquid supply unit 19 .

[0027] <Discharge part> 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 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 in which a nozzle is formed.

[0028] <Volume Changing Means> There are no particular limitations on the volume change means as long as it can change the volume of the liquid storage section, and it can be selected appropriately depending on the purpose. Examples include a piezoelectric element (sometimes called a "piezo element") that expands and contracts when voltage is applied, and an electro-thermal conversion element such as a heating resistor.

[0029] <Means for generating constriction> One example of a constriction generating means is the technology described in JP 2007-199463 A. In the above-mentioned JP 2007-199463 A, a vibration means using a piezoelectric element in contact with a part of a liquid storage portion is used to apply vibration to the liquid storage portion while releasing raw material liquid from a plurality of nozzle holes provided in the liquid storage portion, causing the raw material fluid to go from a columnar shape to a constricted state and then to become droplets.

[0030] <Nozzle Vibration Means> An example of a nozzle vibration means is a method using the technology described in JP 2008-292976 A. The method described in JP 2008-292976 A includes a thin film having a plurality of nozzles formed therein and disposed in a liquid storage section, and piezoelectric elements disposed around the periphery of a deformable region of the thin film to vibrate the thin film, thereby discharging the raw material liquid from the plurality of nozzle holes and forming droplets.

[0031] As an example, a droplet forming device employing a discharge section having a constriction generating means will be described below with reference to Figures 1 and 2. Figure 2 is a partially enlarged view of the discharge section.

[0032] 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 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.

[0033] The ejection section 10 includes an ejection head 100 having a liquid chamber 10A and an ejection hole 102x, and an ejection section main body 110 to which the ejection head 100 is connected. The ejection head 100 may be configured to be detachable from the ejection section main body 110.

[0034] The ejection head 100 is not particularly limited as long as it has a liquid chamber 10A, and the shape, size, etc. can be appropriately selected according to the purpose. The ejection head 100 shown in Figures 1 and 2 is provided at the lower end of the ejection part 10, which has a cylindrical shape. The side surface 100a of the ejection head 100 is a cylindrical surface and is curved.

[0035] In this embodiment, the "side surface" is not limited to a surface parallel to the z axis, but also includes a surface inclined with respect to the z axis so as to face the -z direction. For example, the side surface may have an angle with the z axis of 0° or more and 45° or less. The angle between the side surface and the z axis is preferably 0° or more and 30° or less, and more preferably 0° or more and 15° or less. In addition, the side surface may be a curved surface that is convex in the -z direction.

[0036] The ejection head 100 has a head body in which a liquid chamber 10A is provided, a nozzle plate 102 that forms part of the wall surface of the liquid chamber 10A, and a cover 103 that presses the nozzle plate 102 against the head body and keeps the contact surface between the head body and the nozzle plate 102 liquid-tight.

[0037] The nozzle plate 102 has a plurality of ejection holes 102x. The cross-sectional shape and size of the ejection holes 102x can be appropriately selected.

[0038] 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 shape in which the opening diameter narrows while maintaining a round shape 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 (side from which the liquid is ejected) (4): A combination of the shape of (1) and the shape of (2) The nozzle angle or taper angle may be constant from the inside to the outside, may change continuously, or may change discontinuously (in steps).

[0039] The nozzle angle in the shape of (3) is not particularly limited and can be appropriately selected 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, and processing is also easier. If the nozzle angle is 90° or less, pressure is applied at the discharge hole, so droplet discharge can be stabilized. Therefore, it is preferable to set the maximum value of the nozzle angle to 90°.

[0040] The size of the discharge hole 102x is not particularly limited and can be appropriately selected depending on the purpose. For example, the diameter of the discharge hole 102x is preferably 5 μm or more and 100 μm or less.

[0041] The ejection head 100 has a vibration unit that applies vibration to the raw material liquid stored in the liquid chamber 10A inside. A piezoelectric element is generally used as the vibration unit. There is no particular limitation on the piezoelectric element, and the shape, size, and material can be appropriately selected. For example, a piezoelectric element used in a conventional inkjet ejection method can be suitably used.

[0042] There are no particular limitations on the shape and size of the piezoelectric element, and they can be appropriately selected according to the shape of the ejection hole, etc.

[0043] The material of the piezoelectric element is not particularly limited and can be appropriately selected depending on the purpose. Examples of the material 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.

[0044] 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 section.

[0045] The raw material liquid supply unit 19 has a raw material liquid tank 191 that stores the raw material liquid, a pipe 192 that connects the raw material liquid tank 191 and the ejection head 100, and a pump 193 provided in the path of the pipe 192. The raw material liquid supply unit 19 supplies the raw material liquid L1 stored in the raw material liquid tank 191 to the liquid chamber 10A.

[0046] The means for supplying the raw material liquid L1 from the raw material liquid tank 191 to the liquid chamber 10A may be a pump 192 provided in the piping path, or a pressure applying means for increasing the internal pressure of the raw material liquid tank 191 in order to pump the raw material liquid.

[0047] -Raw material liquid- The raw material liquid is not particularly limited as long as it is a liquid that can be dried and solidified, but it preferably contains a base material, and further contains a solvent and other components as necessary.

[0048] --Base material-- The substrate is a material that is the base that constitutes the particles. Therefore, it is preferable that it is 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, but 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 described above, the substrate may be one type or two or more types, and any substrates described below may be used in combination.

[0049] -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 kinds.

[0050] --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 oils, seasoning oils, water-insoluble vitamins, fatty acids, mixtures thereof, and derivatives thereof. These may be used alone or in combination of two or more.

[0051] --Sugars-- The saccharides are not particularly limited and can be appropriately selected 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 may be used alone or in combination of two or more.

[0052] --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, and cyclodextrin derivatives, etc. These may be used alone or in combination of two or more kinds.

[0053] --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 may be used alone or in combination of two or more.

[0054] --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 may be used alone or in combination of two or more.

[0055] -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, etc. These may be used alone or in combination of two or more kinds.

[0056] --Water-soluble cellulose-- The water-soluble cellulose is not particularly limited and can be appropriately selected according to 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 may be used alone or in combination of two or more. Among these, hydroxypropyl cellulose and hydroxypropyl methyl cellulose are preferred, and hydroxypropyl cellulose is more preferred, because they have high biocompatibility and high solubility in the solvent used to produce the particles.

[0057] ---Hydroxypropyl cellulose--- Hydroxypropyl cellulose is commercially available in various products with different viscosities from various companies, and any of them can be used in the base material of the present invention. The viscosity of a 2% by mass aqueous solution (20°C) of hydroxypropyl cellulose is not particularly limited and can be appropriately selected depending on the purpose, but is preferably 2.0 mPa·s (centipoise, cps) or more and 4,000 mPa·s (centipoise, cps) or less.

[0058] In addition, 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 according to 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).

[0059] Commercially available hydroxypropyl cellulose products are not particularly limited and can be appropriately selected depending on the purpose. Examples include HPC-SSL having a molecular weight of 15,000 to 30,000 and a viscosity of 2.0 to 2.9 mPa·s, HPC-SL having a molecular weight of 30,000 to 50,000 and a viscosity of 3.0 to 5.9 mPa·s, HPC-L having a molecular weight of 55,000 to 70,000 and a viscosity of 6.0 to 10.0 mPa·s, HPC-M having a molecular weight of 110,000 to 150,000 and a viscosity of 150 to 400 mPa·s, and HPC-H having 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 may be used alone or in combination of two or more. Among these, 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 by gel permeation chromatography (GPC), and the viscosity is measured by using a 2% by weight aqueous solution (20°C).

[0060] The content of hydroxypropyl cellulose is not particularly limited and can be appropriately selected 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.

[0061] --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 may be used alone or in combination of two or more.

[0062] --Poly(meth)acrylamide-- The poly(meth)acrylamide is not particularly limited and can be appropriately selected according to the purpose. For example, 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 can be used alone or in combination of two or more. These polymers can be used alone or in combination of two or more.

[0063] --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 may be used alone or in combination of two or more kinds.

[0064] --Poly(meth)acrylic acid ester-- The poly(meth)acrylic acid ester is not particularly limited and can be appropriately selected according to the purpose. For example, 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 can be mentioned. 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.

[0065] --Polyallylamine-- The polyallylamine is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include diallylamine, triallylamine, etc. These may be used alone or in combination of two or more kinds.

[0066] --Polyvinylpyrrolidone-- As polyvinylpyrrolidone, commercially available products can be used. There is no particular limitation on commercially available polyvinylpyrrolidone products, and they can be appropriately selected according to the purpose, and examples thereof include Plasdon 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 may be used alone or in combination of two or more.

[0067] --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 may be used alone or in combination of two or more kinds.

[0068] --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 may be used alone or in combination of two or more kinds.

[0069] --Biodegradable polyester-- The biodegradable polyester is not particularly limited and can be appropriately selected according to the purpose, and examples thereof include polylactic acid; poly-ε-caprolactone; succinate-based polymers such as polyethylene succinate, polybutylene succinate, and polybutylene succinate adipate; polyhydroxyalkanoates such as polyhydroxypropionate, polyhydroxybutyrate, and polyhydroxyparylates, and polyglycolic acid. These may be used alone or in combination of two or more. Among these, polylactic acid is preferred because it has high biocompatibility and can slowly release the physiologically active substance contained therein.

[0070] ---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 from 5,000 to 100,000, more preferably from 10,000 to 70,000, even more preferably from 10,000 to 50,000, and particularly preferably from 10,000 to 30,000.

[0071] The content of polylactic acid is not particularly limited and can be appropriately selected 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, based on the mass of the base material.

[0072] ---Polyglycolic acid--- The polyglycolic acid is not particularly limited and can be appropriately selected depending on the purpose. For example, lactic acid-glycolic acid copolymer, which is a copolymer having a structural unit derived from lactic acid and a structural unit derived from glycolic acid, glycolic acid-caprolactone copolymer, which is a copolymer having a structural unit derived from glycolic acid and a structural unit derived from caprolactone, glycolic acid-trimethylene carbonate copolymer, which is a copolymer having a structural unit derived from glycolic acid and a structural unit derived from trimethylene carbonate, etc. can be used alone or in combination of two or more kinds. Among these, lactic acid-glycolic acid copolymer is preferred because it is highly biocompatible, can slowly release the physiologically active substance contained therein, and can store the physiologically active substance contained therein for a long period of time.

[0073] 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, further preferably 3,000 to 50,000, and particularly preferably 5,000 to 10,000.

[0074] 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 appropriately selected 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.

[0075] The content of the lactic acid / glycolic acid copolymer is not particularly limited and can be appropriately selected 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, based on the mass of the base material.

[0076] --Polyamino acids-- The polyamino acid is not particularly limited and can be appropriately selected according to the purpose. The polyamino acid may be a polymer of any combination of the amino acids exemplified in the above amino acid section, but is preferably a polymer of 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, polyserine, and copolymers thereof. These may be used alone or in combination of two or more.

[0077] --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, etc. These may be used alone or in combination of two or more kinds.

[0078] The natural dispersant polymer used in the gelatin derivative is not particularly limited and can be appropriately selected according to the purpose, and examples thereof include proteins, polysaccharides, and nucleic acids. Among these, copolymers made of natural dispersant polymers or synthetic dispersant polymers are also included. These may be used alone or in combination of two or more.

[0079] The gelatin derivative means 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.

[0080] 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 kinds.

[0081] 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 may be used alone or in combination of two or more kinds.

[0082] 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-mentioned materials, it is preferable that the substrate is a substance that is not biotoxic, and in particular a biodegradable substance such as a biodegradable polymer.

[0083] --solvent-- The solvent is not particularly limited and can be appropriately selected depending on the purpose, but it is preferable to use a solvent that can dissolve or disperse a poorly water-soluble compound or a medicamentically acceptable salt thereof.

[0084] Examples of the solvent 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.), amides (e.g., dimethylformamide, dimethylacetamide, etc.). These may be used alone or in combination of two or more. Among these, from the viewpoint of solubility, aliphatic halogenated hydrocarbons, alcohols, ketones, or mixed solvents thereof are preferred, and dichloromethane, 1,4-dioxane, methanol, ethanol, acetone, or mixed solvents thereof are more preferred.

[0085] The content of the solvent is preferably 70% by mass or more and 99.5% by mass or less, more preferably 90% by mass or more and 99% by mass or less, based on the total amount of the raw material liquid. When the content of the solvent is 70% by mass or more and 99.5% by mass or less, it is advantageous in terms of production stability in terms of the solubility of the material and the solution viscosity.

[0086] --Other ingredients-- The other components are not particularly limited and can be appropriately selected 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 may be used alone or in combination of two or more.

[0087] 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 may be used alone or in combination of two or more.

[0088] 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 may be used alone or in combination of two or more.

[0089] 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, sodium carboxymethyl starch, croscarmellose sodium, crospovidone, hydroxypropyl starch, corn starch, etc. These may be used alone or in combination of two or more.

[0090] 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 may be used alone or in combination of two or more kinds.

[0091] As the light anhydrous silicic acid, a commercially available product can be used. The commercially available light anhydrous silicic acid is not particularly limited and can be appropriately selected according to the purpose, and examples thereof include Adsolider 101 (manufactured by Freund Corporation: average pore size: 21 nm).

[0092] Commercially available products can be used as the adsorbent. There is no particular restriction on the commercially available adsorbent, and it can be appropriately selected according to the purpose. For example, the product name: Carplex (component name: synthetic silica, registered trademark of DSL. Japan Co., Ltd.), the product name: Aerosil (registered trademark of Nippon Aerosil Co., Ltd.) 200 (component name: hydrophilic fumed silica), the product name: Sylysia (component name: amorphous silicon dioxide, registered trademark of Fuji Silysia Chemical Co., Ltd.), the product name: Alkamac (component name: synthetic hydrotalcite, registered trademark of Kyowa Chemical Co., Ltd.), etc. can be mentioned. These may be used alone or in combination of two or more kinds.

[0093] 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 may be used alone or in combination of two or more.

[0094] 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 may be used alone or in combination of two or more kinds.

[0095] 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 may be used alone or in combination of two or more kinds.

[0096] 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 may be used alone or in combination of two or more kinds.

[0097] The colorant 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 may be used alone or in combination of two or more kinds.

[0098] 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 may be used alone or in combination of two or more.

[0099] The masking agent is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include titanium oxide, etc. These may be used alone or in combination of two or more kinds.

[0100] 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 may be used alone or in combination of two or more kinds.

[0101] 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 may be used alone or in combination of two or more.

[0102] 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, and may be in a state in which the solid content contained in the raw material liquid is molten.

[0103] 2, the multiple ejection holes 102x are arranged in a horizontal direction on the side surface 100a of the ejection section 10 (ejection head 100) to form a nozzle row C. Note that the term "horizontal direction" literally refers to a direction parallel to the xy plane in an xyz Cartesian coordinate system, but the arrangement direction of the ejection holes 102x does not have to be strictly parallel to the xy plane in the configuration of the ejection section 10. For example, it may be inclined by about ±10° with respect to the xy plane.

[0104] As described above, the side surface 100a of the discharge head 100 is a cylindrical surface, and the multiple discharge holes 102x are arranged in the circumferential direction of the cylindrical surface. Since the droplets D are discharged from the discharge holes 102x in the radial direction of the discharge head 100, it can be said that the side surface 100a is convex in the discharge direction of the droplets D.

[0105] In the discharge head 100 configured in this way, the droplets D (droplets D1, D2) discharged from adjacent discharge holes 102x move away from each other as they move away from the discharge head 100. Therefore, the droplets D discharged from such a discharge head 100 are prevented from coalescing in the air, which causes a change in particle size, and this is preferable because it makes it easier to maintain the particle size of the droplets D as set.

[0106] 3 is an enlarged view for explaining the arrangement of the ejection holes 102x, in which the curved nozzle plate 102 is stretched out.

[0107] 3, the nozzle plate 102 has a plurality of (two in the figure) first nozzle rows C1 and second nozzle rows C2. Hereinafter, the first nozzle row C1 will be abbreviated as "nozzle row C1" and the second nozzle row C2 will be abbreviated as "nozzle row C2."

[0108] The nozzle rows C1 and C2 are arranged in a direction α that intersects with the extension direction (horizontal direction) of each nozzle row.

[0109] Furthermore, in the nozzle plate 102, the multiple ejection holes 102x included in the nozzle row C1 and the multiple ejection holes 102x included in the nozzle row C2 are spaced apart at equal intervals. Note that the intervals between the multiple ejection holes 102x do not have to be equal.

[0110] Furthermore, the multiple ejection holes 102x included in the nozzle array C1 and the multiple ejection holes 102x included in the nozzle array C2 are arranged in a staggered manner. In Fig. 3, the staggered arrangement refers to an arrangement in which the ejection holes 102x of the nozzle array C1 and the ejection holes 102x of the nozzle array C2 are alternately arranged from one end side to the other end side in the extension direction of the nozzle arrays C1 and C2. Therefore, the ejection hole A of the nozzle array C1 and the ejection holes X1 and X2 of the nozzle array C2 do not overlap in the z-axis direction.

[0111] The arrangement of the discharge holes 102x as described above is designed based on the following concept.

[0112] First, when the raw material liquid is discharged from the discharge hole 102x to form droplets, the raw material liquid adheres to the side surface 100a around the discharge hole 102x, and some of the solid content contained in the raw material liquid L1 precipitates, so that dirt almost inevitably adheres to the side surface 100a. If such dirt accumulates, the discharge hole 102x will not be able to discharge as set, and various discharge defects will occur.

[0113] Possible discharge defects include, for example, the following states (1) to (4). (1) The ejection hole 102x is completely blocked, making it impossible to eject droplets. (2) A part of the discharge hole 102x becomes clogged, and the particle size of the droplets becomes smaller than the set size. (3) Although droplets cannot be discharged from the discharge hole 102x, the raw material liquid is discharged and spreads around the discharge hole 102x. (4) Dirt accumulates on a portion of the edge of the discharge hole 102x, causing the discharge hole 102x to tilt with respect to the central axis.

[0114] Furthermore, if the dirt accumulates, it is expected that the dirt will also affect the discharge holes 102x adjacent to the dirty discharge hole 102x. The dirt on the discharge holes 102x can be removed, for example, by disassembling and cleaning the discharge head 100, but cleaning requires stopping production, which leads to a decrease in productivity.

[0115] The inventors believed that the decrease in productivity due to the stains around the ejection holes 102x generated as described above could be suppressed by changing the design of the ejection head 100, and after various investigations, they completed the present invention.

[0116] First, in the droplet forming device 1 of this embodiment, the discharge hole 102x is provided on the side of the discharge head 100. In the present technical field, there is also a conventional technique in which the discharge hole is provided on the underside of the discharge head. However, in such a configuration, when the droplet is discharged, the raw material liquid adheres isotropically around the discharge hole 102x, and as a result, it is considered that the dirt generated at the discharge hole spreads around the discharge hole isotropically. Therefore, there is a risk that the dirt generated at the discharge hole may affect multiple surrounding discharge holes.

[0117] On the other hand, when the ejection holes 102x are provided on the side surface of the ejection head 100 as in the droplet forming device 1 of this embodiment, the raw material liquid adhering to the periphery of the ejection hole 102x hangs down in the direction of gravity (-z direction). Therefore, even if the raw material liquid spreads to the side surface around a certain ejection hole 102x, it is unlikely to affect the ejection holes 102x included in the same nozzle row C.

[0118] Next, the behavior of the raw material liquid dripping down from the discharge hole 102x will be considered. Fig. 4 is a schematic diagram showing the state around the discharge hole 102x on the side surface 100a.

[0119] The raw material liquid dripping from the discharge hole 102x in the -z direction spreads horizontally as the solvent gradually evaporates, solidifying, and stopping. Figure 4 shows a schematic of such spreading of the raw material liquid. It can be assumed that the raw material liquid dripping from the discharge hole 102x spreads over a range AR of a distance L from the center of the discharge hole 102x and a width W at the bottom end.

[0120] If an adjacent ejection hole 102x (denoted by reference symbol Y1) exists in the range AR of the thus assumed liquid dripping, the ejection hole Y1 is expected to be affected by the liquid dripping and cause ejection defects.

[0121] On the other hand, the discharge hole 102x (denoted by the symbol Y2) that is located outside the range AR even though it is at the same height position as the discharge hole Y1 is expected not to be affected by dripping.

[0122] In the ejection head 100 of the droplet forming device 1, the positions of the multiple ejection holes 102x are set based on the above concept.

[0123] The range AR is considered to be affected by various conditions such as the volatility (vapor pressure) of the solvent contained in the raw material liquid, the concentration of the raw material liquid, the contact angle between the nozzle plate 102 and the raw material liquid, the temperature inside the chamber of the microparticle manufacturing device, and the partial pressure of the solvent inside the chamber. Among these, the temperature and partial pressure inside the chamber, which are operating conditions, are controllable. Therefore, when ejecting the raw material liquid using a specific nozzle plate 102, it is advisable to prepare the raw material liquid through a preliminary experiment and set a recipe for the raw material liquid such that the adjacent ejection holes 102x are not included within the range AR with respect to the arrangement of the ejection holes 102x of the nozzle plate 102.

[0124] The nozzle plate 102 may be designed so that, for a given ejection hole 102x, no adjacent ejection hole 102x is provided within the trajectory of the ejection hole 102x when the ejection hole 102x is translated in the -z direction.

[0125] Further, the nozzle plate 102 shown in the drawing has two nozzle rows C, but this is not limiting, and three or more nozzle rows may be arranged.

[0126] Conversely, the nozzle plate 102 may have only one nozzle row C. In this case, there is a theoretical upper limit to the distance between horizontally adjacent ejection holes 102x, due to the influence of processing accuracy and material strength of the nozzle plate, and from the viewpoint of preventing the formed droplets from coalescing. Therefore, in order to increase the amount of droplets ejected from the ejection head 100, it is better to have multiple nozzle rows C.

[0127] According to the droplet forming device 1 configured as above, it is possible to provide a droplet forming device that is less susceptible to the effects of dirt adhering to the periphery of the nozzle.

[0128] Furthermore, the microparticle production apparatus 500 having the above-mentioned configuration is provided with the droplet forming device, and enables stable production of high-quality microparticles.

[0129] Although the preferred embodiment of the present invention has been described above with reference to the accompanying drawings, the present invention is not limited to the above embodiment. The shapes and combinations of the components shown in the above embodiment are merely examples, and various modifications can be made based on design requirements, etc., without departing from the spirit of the present invention.

[0130] The present invention includes the following aspects.

[0131] [1] A droplet forming device having a discharge head that discharges droplets of a raw material liquid, the discharge head having a plurality of discharge holes, the plurality of discharge holes being formed on a side surface of the discharge head, and each of the plurality of discharge holes being provided at a position on the side surface so as not to overlap with a virtual area within which the raw material liquid is assumed to drip and spread from the discharge holes.

[0132] [2] The droplet forming device according to [1], wherein the plurality of ejection holes form a nozzle row arranged in a horizontal direction.

[0133] [3] The droplet forming device according to [2], further comprising a plurality of the nozzle rows, the plurality of nozzle rows being arranged on the side surface in a direction intersecting with the extension direction of the nozzle rows.

[0134] [4] The droplet forming device according to [3], wherein the plurality of ejection holes included in the first nozzle row and the plurality of ejection holes included in the second nozzle row adjacent to the first nozzle row are arranged in a staggered manner.

[0135] [5] The droplet forming device according to [3] or [4], wherein the plurality of ejection holes included in the nozzle row are spaced apart at equal intervals from one another.

[0136] [6] The droplet forming device according to any one of [1] to [5], wherein the side surface is convex in a direction in which the droplet is ejected.

[0137] [7] The droplet forming device according to [6], wherein the side surface is a cylindrical surface.

[0138] [8] A fine particle manufacturing apparatus comprising: the droplet forming apparatus according to any one of [1] to [7]; and solidification means for solidifying droplets discharged from the droplet forming apparatus. [Explanation of symbols]

[0139] 1...droplet forming device, 100...ejection head, 100a...side surface, 102x, A, X1, X2, Y1, Y2...ejection holes, 500...fine particle manufacturing device, AR...range, C...nozzle row, C1...first nozzle row, C2...second nozzle row, D, D1, D2...droplets, L1...raw material liquid [Prior art documents] [Patent documents]

[0140] [Patent Document 1] JP 2019-177371 A

Claims

1. A nozzle having a nozzle head for ejecting droplets of a raw material liquid for forming fine particles, The ejection head has a plurality of ejection holes, The plurality of ejection holes are formed on a side surface of the ejection head, the plurality of discharge holes are provided at positions on the side surface so as not to overlap with a virtual area in which the raw material liquid is assumed to drip and spread from the discharge holes, The plurality of ejection holes form a nozzle row arranged in a horizontal direction, There are a plurality of the nozzle rows, the nozzle rows are arranged on the side surface in a direction intersecting a direction in which the nozzle rows extend, A droplet forming device, wherein a plurality of ejection holes included in a first nozzle row and a plurality of ejection holes included in a second nozzle row adjacent to the first nozzle row are arranged in a staggered manner.

2. The droplet forming device according to claim 1 , wherein the plurality of ejection holes included in the nozzle row are spaced apart at equal intervals from one another.

3. The droplet forming device according to claim 1 or 2, wherein the side surface is convex in a direction in which the droplets are discharged.

4. The droplet forming device according to claim 3 , wherein the side surface is a cylindrical surface.

5. A droplet forming device; and a solidification means for solidifying the droplets discharged from the droplet forming device, the droplet forming device has a discharge head that discharges droplets of a raw material liquid for fine particles; The ejection head has a plurality of ejection holes, The plurality of ejection holes are formed on a side surface of the ejection head, The plurality of discharge holes are each provided at a position on the side surface that does not overlap with a virtual range in which the raw material liquid is assumed to drip and spread from the discharge hole.

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