Droplet forming apparatus and microparticle manufacturing apparatus

Abstract

A droplet forming apparatus is provided, comprising: a liquid chamber; a discharge orifice for discharging a raw material liquid from the liquid chamber in the form of droplets; a sealing space forming device; and at least two flow paths. The sealing space forming device is capable of forming a sealing space on the side opposite to the liquid chamber of the discharge orifice, communicating with the liquid chamber through the discharge orifice. The at least two flow paths are interconnected through the sealing space.

Description

Technical Field

[0001] This invention relates to droplet forming apparatus and microparticle manufacturing apparatus.

[0002] Priority is claimed to 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

[0003] Microparticles with narrow particle size distributions are used in various applications, such as toner microparticles for electrophotography and isolation particles for liquid crystal panels. Among these, a manufacturing apparatus is known as a device for manufacturing toner microparticles, which discharges liquid toner material in the form of droplets and granulates microparticles with a desired particle size (e.g., Patent Document 1). In the manufacturing apparatus described in Patent Document 1, microparticles with a desired particle size distribution are manufactured by discharging a raw material liquid as microparticle material from a nozzle in the form of droplets and removing the solvent from the droplets. Summary of the Invention

[0004] Technical issues

[0005] As mentioned above, microparticles with a narrow particle size distribution are also used as materials for tablets and capsules, and as carriers for physiologically active substances such as pharmaceutical compounds.

[0006] Pharmaceutical microparticles need to be manufactured in sanitary facilities that comply with Good Manufacturing Practices (GMP). Therefore, it is necessary to effectively clean and maintain the equipment used in manufacturing microparticles to prevent contamination from different chemicals when changing product types and to manufacture microparticles with the designed particle size distribution.

[0007] At the same time, in order to manufacture microparticles industrially, it is desirable to clean the equipment effectively so as not to excessively reduce production efficiency (production per unit time).

[0008] The manufacturing apparatus described in Patent Document 1 describes a structure for cleaning nozzles, but there is room for further improvement in order to keep the apparatus in a suitable state for manufacturing and to effectively clean the apparatus without reducing production efficiency.

[0009] It is important to note that the aforementioned issues are not limited to pharmaceuticals. In the field of microparticle manufacturing, it is typically necessary to suppress contamination from foreign substances and maintain a state suitable for manufacturing the desired microparticles.

[0010] The present invention was made in view of this situation, and its object is to provide a droplet forming apparatus capable of efficiently and effectively cleaning a nozzle, and a microparticle manufacturing apparatus including the droplet forming apparatus and capable of manufacturing high-quality microparticles.

[0011] Solution to the problem

[0012] To address the aforementioned problems, according to one aspect of the present invention, a droplet forming apparatus is provided, comprising: a liquid chamber; a discharge orifice configured to discharge a raw material liquid from the liquid chamber in the form of droplets; a means for forming a sealed space; and at least two flow paths, wherein the means for forming a sealed space on a side opposite to the liquid chamber of the discharge orifice, communicating with the liquid chamber through the discharge orifice, and the at least two flow paths communicating with each other through the sealed space.

[0013] Beneficial effects of the invention

[0014] According to the present invention, a droplet forming apparatus capable of efficiently and effectively cleaning nozzles can be provided. Furthermore, a microparticle manufacturing apparatus including a droplet forming apparatus and capable of producing high-quality microparticles can be provided. Attached Figure Description

[0015] Figure 1 This is an explanatory diagram of a droplet forming device.

[0016] Figure 2 This is an explanatory diagram showing an example of the construction of the switching device 26.

[0017] Figure 3 This is an explanatory diagram depicting the operation of the droplet forming apparatus 1.

[0018] Figure 4 This is an explanatory diagram depicting the operation of the droplet forming apparatus 1.

[0019] Figure 5 This is an explanatory diagram depicting the operation of the droplet forming apparatus 1.

[0020] Figure 6 This is an explanatory diagram depicting the operation of the droplet forming apparatus 1.

[0021] Figure 7 This is an explanatory diagram depicting the operation of the droplet forming apparatus 1.

[0022] Figure 8 This is an explanatory diagram depicting the operation of the droplet forming apparatus 1.

[0023] Figure 9 This is an explanatory diagram of the droplet forming apparatus and the microparticle manufacturing apparatus according to the second embodiment.

[0024] Figure 10This is an explanatory diagram of the droplet forming apparatus according to the second embodiment.

[0025] Figure 11 This is an explanatory diagram of the droplet forming apparatus according to the second embodiment. Detailed Implementation

[0026] [First Embodiment]

[0027] The following will refer to Figures 1 to 8 A droplet forming apparatus according to a first embodiment is described. Furthermore, in all the following figures, the dimensions and proportions of the components have been appropriately altered to make the figures easier to see.

[0028] <<Droplet Formation Device>>

[0029] The droplet forming apparatus of this embodiment includes a droplet discharge unit for discharging raw material liquid and a cleaning unit for cleaning the discharge unit.

[0030] For example, any of the following (1) to (3) as well-known constructions for discharging droplets can be used in the discharging unit.

[0031] (1) Using the construction of a "volume changing device" that uses vibration to change the volume of the liquid containing unit.

[0032] (2) Using a “contraction generating device” structure, the contraction generating device releases liquid from multiple discharge holes provided in the liquid containing unit while applying vibration to the liquid containing unit, and transforms the liquid from a columnar shape into droplets through a contraction state.

[0033] (3) Using a "nozzle vibrating device" structure, the nozzle vibrating device vibrates the thin film in which the discharge hole (nozzle) is formed.

[0034] <Volume Changing Device>

[0035] There are no particular limitations on volume-changing devices, as long as they can change the volume of the liquid-containing unit and can be appropriately selected according to the purpose. Piezoelectric elements (sometimes called "piezoelectric elements") that expand and contract when a voltage is applied, and electrothermal switching elements such as heating resistors are exemplary examples.

[0036] <Contraction Generating Device>

[0037] As a contraction generating device, for example, there are devices that use the technology described in Japanese Unexamined Patent Application No. 2007-199463. In Japanese Unexamined Patent Application No. 2007-199463, a configuration is considered in which, when a vibration device is applied to the liquid containing unit by using a piezoelectric element in contact with a portion of the liquid containing unit, the raw material liquid is released from a plurality of nozzles provided in the liquid containing unit, and the raw material liquid changes from a columnar shape to droplets through a contraction state.

[0038] <Nozzle Vibration Device>

[0039] As a nozzle vibration device, for example, there are devices that use the technology described in Japanese Unexamined Patent Application No. 2008-292976. In Japanese Unexamined Patent Application No. 2008-292976, a configuration is considered in which a thin film having multiple nozzles is formed in a liquid containing unit, and piezoelectric elements for vibrating the thin film are arranged around a deformable region of the thin film. It discharges the feed liquid from the multiple nozzles and turns the feed liquid into droplets.

[0040] As an example, a droplet forming apparatus employing a discharge unit with a shrinkage generating device will be described below with reference to the accompanying drawings.

[0041] Figure 1 This is an explanatory diagram of a droplet forming apparatus. (For example...) Figure 1 As shown, the droplet forming apparatus 1 of this embodiment includes a discharge unit 10 and a cleaning unit 20. Furthermore, the droplet forming apparatus 1 may have a control unit 50 for controlling the operation of each unit.

[0042] <Discharge Unit>

[0043] The discharge unit 10 discharges droplets of the raw material liquid, which will be described later. The discharge unit 10 has a liquid chamber 10A for storing the raw material liquid and a discharge orifice (nozzle) 102x communicating with the liquid chamber 10A. The raw material liquid stored in the liquid chamber 10A is discharged through the discharge orifice 102x and forms spherical shapes in the gas phase due to the surface tension of the raw material liquid.

[0044] The discharge unit 10 has a discharge head 100 and a discharge unit body 110. The discharge head 100 has a liquid chamber 10A and a discharge port 102x. The discharge head 100 is connected to the discharge unit body 110. The discharge head 100 may be configured to be attachable to and detachable from the discharge unit body 110.

[0045] The discharge head 100 is not particularly restricted, as long as a liquid chamber 10A is provided, and its shape, size, etc. can be appropriately selected according to the purpose.

[0046] The discharge head 100 has a head body 101 with a liquid chamber 10A and a nozzle plate 102 forming part of the wall surface of the liquid chamber 10A.

[0047] The nozzle plate 102 has multiple discharge holes 102x. The cross-sectional shape and size of the discharge holes 102x can be appropriately selected.

[0048] There are no particular restrictions on the cross-sectional shape of the discharge port 102x, and it can be appropriately selected according to the purpose.

[0049] (1): A conical shape in which the opening diameter decreases from the inside (liquid chamber side) to the outside (liquid discharge side).

[0050] (2): The opening diameter narrows from the inner side (liquid chamber side) to the outer side (liquid discharge side) and has a circular shape.

[0051] (3): A shape in which the opening diameter narrows from the inside (liquid chamber side) to the outside (liquid discharge side) while maintaining a constant nozzle angle.

[0052] (4): Combination of shape (1) and shape (2)

[0053] This is a typical example. Among them, shape (3) is preferred because the pressure of the liquid applied to the discharge hole 102x is the greatest.

[0054] The nozzle angle in shape (3) is not particularly limited and can be appropriately selected according to the purpose, but is preferably 60° or greater and 90° or less. When the nozzle angle is 60° or greater, it is easy to apply pressure to the liquid and easy to process. When the nozzle angle is 90° or less, pressure is applied to the discharge orifice, so the discharge of droplets can be stable. Therefore, it is preferred that the maximum nozzle angle is 90°.

[0055] There are no particular limitations on the size of the discharge port 102x, and it can be appropriately selected according to the purpose. For example, the diameter of the discharge port 102x is preferably 5 micrometers or larger and 100 micrometers or smaller.

[0056] The discharge head 100 is preferably configured to be detachable into a head body 101 and a nozzle plate 102. In the discharge head 100 with this configuration, the liquid chamber 10A can be kept clean by washing after disassembly if necessary.

[0057] The discharge head 100 has a vibration unit 15 that applies vibration to the raw material liquid stored in the liquid chamber 10A. A piezoelectric element is typically used as the vibration unit 15. There are no particular limitations on the piezoelectric element, and its shape, size, and material can be appropriately selected. For example, piezoelectric elements used in conventional inkjet discharge systems can be appropriately used.

[0058] There are no particular restrictions on the shape and size of piezoelectric elements, and they can be appropriately selected according to the shape of the discharge port, etc.

[0059] There are no particular restrictions on the materials used in piezoelectric elements; appropriate materials can be selected depending on the purpose. Examples of exemplary materials include piezoelectric ceramics such as lead zirconate titanate (PZT), piezoelectric polymers such as polyvinylidene fluoride (PVDF), crystals, and single crystals such as LiNbO3, LiTaO3, and KNbO3.

[0060] The discharge head 100 can discharge the raw material liquid from the liquid chamber 10A through the discharge hole 102x, while the vibration unit 15 applies vibration to the raw material liquid in the liquid chamber 10A to turn the raw material liquid into droplets.

[0061] Furthermore, the discharge unit 10 has a raw material supply unit 19 for supplying raw material liquid to the discharge head 100. The raw material supply unit 19 has a raw material tank 191 for storing raw material liquid. The device for supplying raw material liquid from the raw material tank 191 to the liquid chamber 10A can be a pump installed in the pipeline route, or a pressurizing device for increasing the internal pressure of the raw material tank 191 in order to pump the raw material liquid.

[0062] -raw material solution-

[0063] The feed solution contains a base material and, if necessary, solvents and other components.

[0064] --Substrate--

[0065] The substrate is the material used as the basis for the particles. Therefore, it is preferred that the substrate is solid at room temperature. There are no particular limitations on the substrate, as long as it does not adversely affect the physiologically active substances contained therein, and it can be a low molecular weight substance or a high molecular weight substance. However, since the particles of the present invention are preferably particles applicable to living organisms, the substrate is preferably a substance that is non-toxic to living organisms. Preferably, the low molecular weight substance is a compound with a weight average molecular weight of less than 15,000. Preferably, the high molecular weight substance is a compound with a weight average molecular weight of 15,000 or higher. As mentioned above, the number of substrates can be one or more, and any substrates described later can be used in combination.

[0066] -Low molecular weight substances-

[0067] There are no particular restrictions on low molecular weight substances; they can be selected appropriately according to the purpose. Lipids, sugars, cyclodextrins, amino acids, organic acids, etc., are exemplary examples. One of these can be used alone, or two or more of them can be used together.

[0068] --Lipids--

[0069] There are no particular restrictions on lipids; they can be selected appropriately depending on the purpose. Examples include medium-chain or long-chain monoglycerides, medium-chain or long-chain diglycerides, medium-chain 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, and sunflower oil), fish oil, flavoring oils, water-insoluble vitamins, fatty acids, mixtures thereof, and derivatives thereof. One of these lipids may be used alone, or two or more may be used together.

[0070] --sugar--

[0071] There are no particular restrictions on the sugars used; appropriate selection can be made according to the purpose. In addition to monosaccharides and polysaccharides, such as glucose, mannose, idole, galactose, fucose, ribose, xylose, lactose, sucrose, maltose, trehalose, turaose, raffinose, maltotriose, acarbose, cyclodextrin, amylose (starch), and cellulose; sugar alcohols (polyols), such as glycerol, sorbitol, lactitol, maltitol, mannitol, xylitol, and erythritol; and their derivatives are exemplary examples. One of these sugars can be used alone, or two or more can be used together.

[0072] --Cyclodextrin--

[0073] There are no particular limitations on cyclodextrins; they can be selected appropriately depending on the purpose. Hydroxypropyl-β-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, α-cyclodextrin, cyclodextrin derivatives, etc., are exemplary examples. One of these cyclodextrins can be used alone, or two or more of them can be used together.

[0074] --amino acids--

[0075] There are no particular restrictions on the amino acids used; they can be selected appropriately according to the purpose. Valine, lysine, leucine, threonine, isoleucine, asparagine, glutamine, phenylalanine, aspartic acid, serine, glutamic acid, methionine, arginine, glycine, alanine, tyrosine, proline, histidine, cysteine, tryptophan, and their derivatives are exemplary examples. One of these amino acids can be used alone, or two or more can be used together.

[0076] --Organic acids--

[0077] There are no particular restrictions on organic acids; they can be selected appropriately according to the purpose. Adipic acid, ascorbic acid, citric acid, fumaric acid, gallic acid, glutaric acid, lactic acid, malic acid, maleic acid, succinic acid, tartaric acid, and their derivatives are exemplary examples. One of these organic acids can be used alone, or two or more of them can be used together.

[0078] -High molecular weight substances-

[0079] There are no particular restrictions on high molecular weight substances; they can be selected appropriately according to the purpose. Examples of exemplary substances include proteins such as water-soluble cellulose, polyalkylene glycols, poly(meth)acrylamide, poly(meth)acrylic acid, poly(meth)acrylate, polyallylamine, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, biodegradable polyesters, polyglycolic acid, polyamino acids, gelatin and fibroin, polysaccharides, and their derivatives. One of these high molecular weight substances can be used alone, or two or more can be used together.

[0080] --Water-soluble cellulose--

[0081] There are no particular limitations on the water-soluble cellulose; it can be appropriately selected according to the purpose. Alkyl cellulose, such as methylcellulose and ethylcellulose; hydroxyalkyl cellulose, such as hydroxyethylcellulose and hydroxypropylcellulose; hydroxyalkylalkyl cellulose, such as hydroxyethylmethylcellulose and hydroxypropylmethylcellulose, etc., are exemplary examples. One of these water-soluble celluloses can be used alone, or two or more of them can be used together. Among these water-soluble celluloses, hydroxypropylcellulose and hydroxypropylmethylcellulose are preferred from the viewpoint of high biocompatibility and high solubility in solvents used to manufacture particles, with hydroxypropylcellulose being more preferred.

[0082] ---Hydroxypropyl cellulose---

[0083] Various hydroxypropyl cellulose products with different viscosities are available from various companies, and any of them can be used as the substrate 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 appropriately selected according to the purpose, but a viscosity of 2.0 mPa·s (centipoise, cps) or higher and 4000 mPa·s (centipoise, cps) or lower is preferred.

[0084] Furthermore, the viscosity of hydroxypropyl cellulose is considered to depend on its weight-average molecular weight, degree of substitution, and molecular weight. There are no particular limitations on the weight-average molecular weight of hydroxypropyl cellulose, which can be appropriately selected according to the purpose, but a weight-average molecular weight of 15,000 to 400,000 is preferred. Moreover, the weight-average molecular weight can be measured using, for example, gel permeation chromatography (GPC).

[0085] There are no particular restrictions on commercially available hydroxypropyl cellulose products; you can choose the appropriate one depending on your purpose. HPC-SSL has a molecular weight of 15,000 or more and 30,000 or less, and a viscosity of 2.0 mPa·s or more and 2.9 mPa·s or less; HPC-SL has a molecular weight of 30,000 or more and 50,000 or less, and a viscosity of 3.0 mPa·s or more and 5.9 mPa·s or less; HPC-L has a molecular weight of 55,000 or more and 70,000 or less, and a viscosity of 6.0 mPa·s or more and 10.0 mPa·s or less; HPC-M has a molecular weight of 110,000 or more and 150,000 or less, and a viscosity of 150 mPa·s or more and 400 mPa·s or less; HPC-M has a molecular weight of 250,000 or more and 400,000 or less, and a viscosity of 1,000 mPa·s or more and 4,000 mPa·s or less, etc. (Nippon Soda Co., Ltd.) (Manufactured by Co., Ltd.) is an exemplary example. One of these hydroxypropyl celluloses can be used alone, or two or more can be used together. Among these hydroxypropyl celluloses, HPC-SSL with a molecular weight of 15,000 or more and 30,000 or less, and a viscosity of 2.0 mPa·s or more and 2.9 mPa·s or less, is preferred. Furthermore, in the above-mentioned commercially available products, the molecular weight was measured using gel permeation chromatography (GPC), and the viscosity was measured using a 2% by mass aqueous solution (20°C).

[0086] There is no particular limitation on the content of hydroxypropyl cellulose, which can be selected appropriately according to the purpose. Regarding the quality of the base material, a content of 50% by mass or more is preferred, a content of 50% by mass or more but less than 99% by mass is more preferred, a content of 75% by mass or more but less than 99% by mass is more preferred, and a content of 80% by mass or more but less than 99% by mass is particularly preferred.

[0087] --Polyalkylene glycol--

[0088] There are no particular limitations on polyalkylene glycols; they can be selected appropriately depending on the purpose. Polyethylene glycol (PEG), polypropylene glycol, polybutanediol, and copolymers thereof are exemplary examples. One of these polyalkylene glycols can be used alone, or two or more of them can be used together.

[0089] --Poly(meth)acrylamide--

[0090] Poly(meth)acrylamide is not particularly limited and can be appropriately selected according to the purpose. 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-(aminosulfonylphenyl)(meth)acrylamide, N-(benzenesulfonyl)(meth)acrylamide, N-(toluenesulfonyl)(meth)acrylamide, N,N-dimethyl(meth)acrylamide, N-methyl-N-phenyl(meth)acrylamide, and N-hydroxyethyl-N-methyl(meth)acrylamide are exemplary examples. One of these monomers can be polymerized alone, or two or more of them can be polymerized together. Furthermore, one of these polymers can be used alone, or two or more of them can be used together.

[0091] --Poly(meth)acrylic acid--

[0092] There are no particular limitations on poly(meth)acrylic acid; it can be selected appropriately depending on the purpose. Homopolymers such as polyacrylic acid and polymethacrylic acid, and copolymers such as acrylic acid-methacrylic acid copolymers are exemplary examples. One of these poly(meth)acrylic acids can be used alone, or two or more of them can be used together.

[0093] --Poly(meth)acrylate--

[0094] Poly(meth)acrylates are not particularly limited and can be appropriately selected according to the purpose. 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-butanediol di(meth)acrylate are exemplary examples. One of these monomers can be polymerized alone, or two or more of them can be polymerized together. Furthermore, one of these polymers can be used alone, or two or more of them can be used together.

[0095] --Polyallylamine--

[0096] There are no particular limitations on polyallylamines; they can be selected appropriately depending on the purpose. Diallylamine and triallylamine are exemplary examples. One of these polyallylamines can be used alone, or two or more of them can be used together.

[0097] --Polyvinylpyrrolidone--

[0098] Commercially available products can be used as polyvinylpyrrolidone. There are no particular restrictions on commercially available polyvinylpyrrolidone products; appropriate selection can be made depending on the purpose. Plasdone C-15 (manufactured by ISP TECHNOLOGIES); Kollidon VA64, Kollidon K-30, and Kollidon CL-M (manufactured by KAWARLAL); Kollicoat IR (manufactured by BASF) are exemplary examples. One of these polyvinylpyrrolidones can be used alone, or two or more can be used together.

[0099] --Polyvinyl alcohol--

[0100] There are no particular limitations on polyvinyl alcohol (PVA), and it can be selected appropriately depending on the purpose. Silane-modified PVA, carboxyl-modified PVA, acetyl-modified PVA, etc., are exemplary examples. One of these PVAs can be used alone, or two or more of them can be used together.

[0101] --Polyvinyl acetate--

[0102] There are no particular limitations on polyvinyl acetate; it can be selected appropriately depending on the purpose. Vinyl acetate-crotonic acid copolymers, vinyl acetate-itaconic acid copolymers, etc., are exemplary examples. One of these polyvinyl acetates can be used alone, or two or more of them can be used together.

[0103] --Biodegradable polyester--

[0104] There are no particular limitations on biodegradable polyesters; they can be appropriately selected depending on the purpose. Exemplary examples include polylactic acid (PLA); poly(ε-caprolactone); succinate polymers such as polyethylene succinate, polybutylene succinate, and polybutylene adipate; polyhydroxyalkanoates such as polyhydroxypropionate, polyhydroxybutyrate, and polyhydroxypalmitate; and polyglycolic acid. One of these biodegradable polyesters can be used alone, or two or more can be used together. PLA is preferred from the perspective of high biocompatibility and the ability to elute physiologically active substances in a controlled release manner.

[0105] ---Polylactic acid---

[0106] There are no particular limitations on the weight-average molecular weight of polylactic acid (PLA), and it can be selected appropriately according to the purpose. A weight-average molecular weight of 5,000 or more and 100,000 or less is preferred, a weight-average molecular weight of 10,000 or more and 70,000 or less is more preferred, a weight-average molecular weight of 10,000 or more and 50,000 or less is still more preferred, and a weight-average molecular weight of 10,000 or more and 30,000 or less is particularly preferred.

[0107] There is no particular limitation on the content of polylactic acid (PLA), and it can be selected appropriately according to the purpose. Regarding the quality of the substrate, a content of 50% by mass or more is preferred, a content of 50% by mass or more but less than 99% by mass is more preferred, a content of 75% by mass or more but less than 99% by mass is still more preferred, and a content of 80% by mass or more but less than 99% by mass is particularly preferred.

[0108] ---Polyglycolic Acid---

[0109] Polyglycolic acid is not particularly limited and can be appropriately selected according to the purpose. Examples include lactic acid / glycolic acid copolymers, which are copolymers having structural units derived from lactic acid and structural units derived from glycolic acid; glycolic acid / caprolactone copolymers, which are copolymers having structural units derived from glycolic acid and structural units derived from caprolactone; and glycolic acid / trimethylene carbonate copolymers, which are copolymers having structural units derived from glycolic acid and structural units derived from trimethylene carbonate. One of these polyglycolic acids can be used alone, or two or more can be used together. Lactic acid / glycolic acid copolymers are preferred from the perspectives of high biocompatibility, the ability to elute physiologically active substances in a controlled release manner, and the long-term preservation of the physiologically active substances contained therein.

[0110] There are no particular limitations on the weight-average molecular weight of the lactic acid / glycolic acid copolymer, and it can be appropriately selected according to the purpose. A weight-average molecular weight of 2,000 to 250,000 is preferred, 2,000 to 100,000 is more preferred, 3,000 to 50,000 is still more preferred, and 5,000 to 10,000 is particularly preferred.

[0111] In lactic acid / glycolic acid copolymers, the molar ratio (L:G) between lactic acid-derived structural units (L) and glycolic acid-derived structural units (G) is not particularly limited and can be appropriately selected according to the purpose. A molar ratio of 1:99 to 99:1 is preferred, a molar ratio of 25:75 to 99:1 is more preferred, a molar ratio of 30:70 to 90:10 is more preferred, and a molar ratio of 50:50 to 85:15 is particularly preferred.

[0112] There are no particular limitations on the content of the lactic acid / glycolic acid copolymer, which can be appropriately selected according to the purpose. Regarding the quality of the substrate, a content of 50% by mass or more is preferred, a content of 50% by mass or more but less than 99% by mass is more preferred, a content of 75% by mass or more but less than 99% by mass is still more preferred, and a content of 80% by mass or more but less than 99% by mass is particularly preferred.

[0113] --Polyamino acids--

[0114] There are no particular limitations on the polyamino acids used; they can be appropriately selected depending on the purpose. Polyamino acids can be polymers obtained by combining the amino acids listed in the amino acid section above in any way, but are preferably polymers 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, copolymers thereof, etc., which are exemplary examples. One of these polyamino acids can be used alone, or two or more of them can be used together.

[0115] --gelatin--

[0116] There are no particular limitations on gelatin; it can be selected appropriately depending on the purpose. Lime-treated gelatin, acid-treated gelatin, gelatin hydrolysates, gelatin enzyme dispersions, and their derivatives are exemplary examples. One of these gelatins can be used alone, or two or more can be used together.

[0117] There are no particular limitations on the natural dispersant polymers used in gelatin derivatives; they can be appropriately selected depending on the purpose. Proteins, polysaccharides, nucleic acids, etc., are exemplary examples. These include natural dispersant polymers or copolymers composed of synthetic dispersant polymers. One of these natural dispersant polymers can be used alone, or two or more can be used together.

[0118] Gelatin derivatives refer to gelatin derived by covalently attaching hydrophobic groups to gelatin molecules. There are no particular limitations on the hydrophobic groups; they can be appropriately selected depending on the purpose. Exemplary examples include polyesters, such as polylactic acid, polyglycolic acid, and poly(ε-caprolactone); lipids, such as cholesterol and phosphatidylethanolamine; aromatic groups containing alkyl groups and benzene rings; heteroaromatic groups, mixtures thereof, etc.

[0119] There are no particular restrictions on proteins, provided they do not adversely affect the physiological activity of the physiologically active substances, and appropriate proteins can be selected according to the purpose. Collagen, fibrin, albumin, etc., are exemplary examples. One of these can be used alone, or two or more of them can be used together.

[0120] There are no particular restrictions on polysaccharides; they can be selected appropriately depending on the purpose. Chitin, deacetylated chitosan, hyaluronic acid, alginate, starch, pectin, etc., are exemplary examples. One of these polysaccharides can be used alone, or two or more of them can be used together.

[0121] The substrate is preferably a substance that allows the particles containing the substrate to be included in pharmaceutical preparations, functional foods, functional cosmetics, etc. Among these materials, non-biotoxic substances, especially biodegradable substances such as biodegradable polymers, are preferred.

[0122] --Solvent--

[0123] There are no particular restrictions on the solvent, and it can be selected appropriately according to the purpose, but solvents that can dissolve or disperse poorly water-soluble compounds or their pharmaceutically acceptable salts are preferred.

[0124] Examples of solvents include aliphatic halogenated hydrocarbons (e.g., dichloromethane, dichloroethane, and chloroform), alcohols (e.g., methanol, ethanol, and propanol), ketones (e.g., acetone and methyl ethyl ketone), ethers (e.g., diethyl ether, dibutyl ether, and 1,4-diane), aliphatic hydrocarbons (e.g., n-hexane, cyclohexane, and n-heptane), aromatic hydrocarbons (e.g., benzene, toluene, and xylene), organic acids (e.g., acetic acid and propionic acid), esters (e.g., ethyl acetate), and amides (e.g., dimethylformamide and dimethylacetamide). One of these can be used alone, or two or more can be used together. From a solubility perspective, aliphatic halogenated hydrocarbons, alcohols, ketones, or mixtures thereof are preferred solvents, with dichloromethane, 1,4-dioxane, methanol, ethanol, acetone, or mixtures thereof being more preferred.

[0125] The solvent content, relative to the total amount of the raw material liquid, 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. From the perspective of material solubility and solution viscosity, a solvent content of 70% by mass or more and 99.5% by mass or less is advantageous in terms of production stability.

[0126] --Other Ingredients--

[0127] There are no special restrictions on other ingredients; they can be selected appropriately according to the purpose.

[0128] Other ingredients include water, excipients, flavoring agents, disintegrants, fluidizing agents, adsorbents, lubricants, flavoring agents, surfactants, fragrances, coloring agents, antioxidants, masking agents, antistatic agents, and humectants, among others. One of these ingredients may be used alone, or two or more may be used together.

[0129] There are no particular restrictions on excipients; they can be selected appropriately depending on the purpose. Examples include lactose, sucrose, mannitol, glucose, fructose, maltose, erythritol, maltitol, xylitol, palaginose, trehalose, sorbitol, crystalline cellulose, talc, anhydrous silicate, anhydrous calcium phosphate, precipitated calcium carbonate, and calcium silicate. One of these excipients can be used alone, or two or more can be used together.

[0130] There are no particular restrictions on flavoring agents; appropriate selection can be made according to the purpose. Examples include L-menthol, sucrose, D-sorbitol, xylitol, citric acid, ascorbic acid, tartaric acid, malic acid, aspartame, acesulfame potassium, sematinine, sodium saccharin, dipotassium glycyrrhizate, monosodium glutamate, sodium 5'-inosinate, and sodium 5'-guanylate. One of these flavoring agents can be used alone, or two or more can be used together.

[0131] There are no particular limitations on the disintegrant; it can be selected appropriately depending on the purpose. Low-substituted hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl starch, croscarmellose sodium, croscarmellose, hydroxypropyl starch, corn starch, etc., are exemplary examples. One of these disintegrants can be used alone, or two or more can be used together.

[0132] There are no particular limitations on the fluidizing agent; it can be selected appropriately depending on the purpose. Light anhydrous silica, hydrated silica, talc, etc., are exemplary examples. One of these fluidizing agents can be used alone, or two or more of them can be used together.

[0133] Commercially available products can be used as light anhydrous silica. There are no particular restrictions on commercially available light anhydrous silica; appropriate products can be selected depending on the purpose. Adsolider 101 (manufactured by Freund Corporation: average pore size: 21 nm) is an exemplary example.

[0134] Commercially available products can be used as adsorbents. There are no particular limitations on commercially available adsorbents; appropriate selection can be made depending on the purpose. Examples of such products include: Carplex (composition: synthetic silica, a registered trademark of DSL Japan Ltd.), Aerosil (a registered trademark of Aerosil Japan Ltd.) 200 (composition: hydrophilic fumed silica), Silysia (composition: amorphous silica, a registered trademark of Fuji Silysia Chemical Co., Ltd.), Alkamac (composition: synthetic hydrotalcite, a registered trademark of Kyowa Kagaku Kogyo Ltd.), and so on. One of these adsorbents can be used alone, or two or more can be used together.

[0135] There are no particular limitations on lubricants; appropriate selection can be made depending on the purpose. Magnesium stearate, calcium stearate, sucrose fatty acid esters, sodium stearoyl fumarate, stearic acid, polyethylene glycol, talc, etc., are exemplary examples. One of these lubricants can be used alone, or two or more of them can be used together.

[0136] There are no particular restrictions on flavorings; they can be selected appropriately depending on the purpose. Trehalose, malic acid, maltose, potassium gluconate, anise essential oil, vanilla essential oil, cardamom essential oil, etc., are exemplary examples. One of these flavorings can be used alone, or two or more of them can be used together.

[0137] There are no particular limitations on surfactants; they can be selected appropriately depending on the purpose. Polysorbates, such as polysorbate 80; polyoxyethylene / polyoxypropylene copolymers; sodium lauryl sulfate, etc., are exemplary examples. One of these surfactants can be used alone, or two or more of them can be used together.

[0138] There are no particular restrictions on spices; they can be selected appropriately depending on the purpose. Lemon oil, orange oil, peppermint oil, etc., are exemplary examples. One of these spices can be used alone, or two or more can be used together.

[0139] There are no particular restrictions on colorants; they can be selected appropriately depending on the purpose. Titanium oxide, Food Yellow No. 5, Food Blue No. 2, iron oxide, yellow iron oxide, etc., are exemplary examples. One of these colorants can be used alone, or two or more of them can be used together.

[0140] There are no particular limitations on antioxidants; they can be selected appropriately depending on the purpose. Sodium ascorbate, L-cysteine, sodium sulfite, and vitamin E are exemplary examples. One of these antioxidants can be used alone, or two or more can be used together.

[0141] There are no particular limitations on the masking agent; it can be selected appropriately depending on the purpose. Titanium oxide and the like are exemplary examples. One of these masking agents can be used alone, or two or more of them can be used together.

[0142] There are no particular limitations on antistatic agents; they can be selected appropriately depending on the purpose. Talc, titanium dioxide, etc., are exemplary examples. One of these antistatic agents can be used alone, or two or more of them can be used together.

[0143] There are no particular limitations on wetting agents; they can be selected appropriately depending on the purpose. Polysorbate 80, sodium lauryl sulfate, sucrose fatty acid esters, polyethylene glycol, hydroxypropyl cellulose (HPC), etc., are exemplary examples. One of these wetting agents can be used alone, or two or more can be used together.

[0144] As the feedstock, a solution in which the physiologically active substance is dissolved in a solvent, or a dispersion in which the physiologically active substance is dispersed in a dispersion medium, can be used. Furthermore, the feedstock may not contain a solvent, provided that it is a liquid under discharge conditions and can be a liquid in which the solid components contained in the feedstock are melted.

[0145] <Cleaning Unit>

[0146] The cleaning unit 20 has a sealed space forming device 21 and a flow unit 22.

[0147] The sealing space forming device 21 can liquid-tightly form a sealing space 21A outside the discharge unit 10. The sealing space 21A communicates with the liquid chamber 10A through the discharge hole 102x. Specifically, the sealing space forming device 21 has a recess 21x on the side facing the discharge head 100, and the upper end 21A of the sidewall surrounding the recess 21x is in liquid-tight contact with the lower surface 100a of the discharge head 100. The space surrounded by the recess 21x and the lower surface 100a is the sealing space 21A. The term "sealed" in sealing space 21A means that the upper end 21A and the lower surface 100a are in liquid-tight contact with each other, so that no liquid leaks from the contact portion.

[0148] The sealing space forming device 21 may have an O-ring or seal (not shown) at the upper end 21a.

[0149] The sealing space forming device 21 is configured to be attachable to and detachable from the lower surface 100a.

[0150] The flow unit 22 allows the cleaning fluid to flow through the liquid chamber 10A and the sealed space 21A, and cleans the outer wall and inner wall of the liquid chamber 10A.

[0151] Polar organic solvents can be used as cleaning solutions, and alcohols such as methanol and ethanol, as well as ketones such as acetone and methyl ethyl ketone, can be suitable. Liquids of the same type as those described above can be used as solvents that can be included in the feed solution as cleaning solutions.

[0152] The flow unit 22 includes a cleaning fluid supply unit 23, a waste liquid injection 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 device 26. Two flow paths are obtained 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 by combining the third flow path 253 and the fourth flow path 254; this corresponds to "at least two flow paths" in this invention. The first flow path 251, the second flow path 252, the third flow path 253, and the fourth flow path 254 consist of through holes formed in the discharge head 100 and pipes connected to the discharge head 100.

[0153] The cleaning fluid supply unit 23 supplies cleaning fluid to the liquid chamber 10A and the sealed space 21A. The cleaning fluid supply unit 23 includes a cleaning fluid tank 231 for storing the cleaning fluid. The device for supplying the cleaning fluid from the cleaning fluid tank 231 to the liquid chamber 10A and the sealed space 21A can be a pump installed in the pipeline, or a pressurizing device for increasing the internal pressure of the cleaning fluid tank 231 to pump the cleaning fluid.

[0154] Waste liquid injection unit 24 injects waste liquid generated by passing through cleaning liquid chamber 10A and sealed space 21A. Waste liquid injection unit 24 includes waste liquid tank 241 for storing waste liquid. The device for injecting waste liquid from liquid chamber 10A and sealed space 21A into waste liquid tank 241 can be a pump installed in the pipeline or a pressurizing device installed in cleaning liquid supply unit 23.

[0155] 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 respectively connected to the cleaning fluid supply unit 23 and the waste liquid injection unit 24 via the switching device 26.

[0156] The third flow path 253 and the fourth flow path 254 are positioned to connect to the sealing space 21A when the sealing space forming device 21 forms the sealing space 21A. The third flow path 253 and the fourth flow path 254 are respectively connected to the cleaning fluid supply unit 23 and the waste liquid injection unit 24 via the switching device 26.

[0157] The switching device 26 is connected to the raw material liquid supply unit 19, the cleaning liquid supply unit 23 and the waste liquid injection unit 24, and switches the flow direction of the raw material liquid, the cleaning liquid and the waste liquid.

[0158] Figure 2 This is an explanatory diagram showing an example of the construction of the switching device 26. (As shown) Figure 2 As shown, the switching device 26 has switching valves SV1 to SV10. In each switching valve, the ON control route is represented by a dashed line, and the OFF control route is represented by a solid line.

[0159] Furthermore, in switching valves SV1, SV4, SV6, and SV8, the pipelines are closed during OFF control. As a result, the first flow path 251, the second flow path 252, the third flow path 253, and the fourth flow path 254 can be closed by closing each switching valve.

[0160] Figure 2Reference numerals P1, P2, and P3 in the accompanying drawings denote pressurizing devices for flowing pressurized gas in tanks and pipes. Pressure is applied through the pressurizing devices to the first flow path 251, the second flow path 252, the third flow path 253, the fourth flow path 254, and the discharge port. The pressure applied to each flow path and the discharge port can be measured by a pressure measuring instrument 259 installed in the first flow path 251. Preferably, the pressure measuring instrument 259 is installed as close as possible to the discharge port in the first flow path. Furthermore, a pressure measuring instrument 260 can be installed in the third flow path 253 to measure the pressure in the sealed space 21A.

[0161] exist Figure 2 In the switching device 26 shown, for example, when the raw material liquid L1 is supplied from the raw material liquid tank 191 to the first flow path 251 and the droplets are discharged from the discharge port, it can be seen that the switching valves SV1, SV2 and SV3 can be opened, all the remaining switching valves can be closed, and the raw material liquid tank 191 can be pressurized from the pressurizing device P1.

[0162] In addition, by appropriately switching the switching valve, the flow paths of the raw material liquid L1, cleaning liquid L2 and waste liquid L3 can be appropriately switched.

[0163] Furthermore, the cleaning fluid tank 231 storing the cleaning fluid L2 and the raw material tank 191 storing the raw material fluid L1 can be switched to the first flow path 251. As a result, the number of pipes can be reduced, and the device structure can be simplified.

[0164] <Control Unit>

[0165] Figure 1 The control unit 50 shown 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 included in the droplet forming device 1, or it may be a general-purpose external PC.

[0166] Figures 3 to 8 This is an explanatory diagram depicting the operation of the droplet forming apparatus 1. In the droplet forming apparatus 1, droplets can be formed by discharging the raw material liquid, and contaminants originating from the raw material liquid on the discharge unit 10 can be easily cleaned without disassembly.

[0167] The following operational description will describe the flow of the liquid, while appropriately illustrating the processes included... Figure 2 The control state of the switching valve in the switching device 26 shown. The operation of each unit described below is based on the control signal provided from the control unit 50.

[0168] like Figure 3As shown, in the droplet forming apparatus 1, with the switching valve SV4 closed to shut off the second flow path 252 and the switching valves SV1, SV2, and SV3 open, the raw material liquid L1 is supplied from the raw material 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 discharge head 100 and discharged from the discharge port 102x.

[0169] At this time, by generating vibration in the vibration unit 15 while supplying raw material liquid L1, the raw material liquid L1 discharged from the discharge hole 102x is discharged in the form of droplets D.

[0170] When the discharge of droplet D is repeated as described above, some of the solid components contained in the raw material liquid L1 may precipitate, and contaminants W1 and W2 may adhere to the outer wall (outer surface 102a of nozzle plate 102) and inner wall (inner surface 102b of nozzle plate 102) of liquid chamber 10A.

[0171] There are concerns that contaminants W1 and W2 will mix with the particles produced using the droplet forming apparatus 1, reducing their mass. Furthermore, there are concerns that when contaminants W1 and W2 clog the discharge orifice 102x, the particle size of the droplets D to be formed will not be as set. Additionally, there are concerns that when contaminants W1 and W2 clog the discharge orifice 102x, the discharge rate of droplets D will deteriorate, leading to a decrease in productivity.

[0172] In the droplet forming device 1, the cleaning unit 20 can be used to easily clean the contaminants from the discharge unit 10.

[0173] (First cleaning (drain hole cleaning))

[0174] First, such as Figure 4 As shown, the sealing space forming device 21 contacts the lower surface 100a of the discharge head 100 to form a sealing space 21A. Next, the second flow path 252 and the third flow path 253 are closed by closing the switching valves SV4 and SV6.

[0175] In this state, another switching valve is controlled to supply cleaning fluid L2 from cleaning fluid supply unit 23 to first flow path 251. Cleaning fluid L2 is supplied from first flow path 251 to liquid chamber 10A and further supplied to sealing space 21A through discharge port 102x.

[0176] In addition, the waste liquid L3 discharged from the sealed space 21A is discharged into the waste liquid tank 241 through the fourth flow path 254.

[0177] As a result, the cleaning fluid can flow from the inside of the liquid chamber 10A to the outside of the liquid chamber 10A to clean the liquid chamber 10A and the sealed space 21A. Due to the flow of the cleaning fluid L2, the contaminants W1 adhering to the outer surface 102a are mainly lifted or peeled off from the outer surface 102a.

[0178] (Second cleaning (external surface cleaning))

[0179] Next, as Figure 5 As shown, the second flow path 252 is closed by closing the switching valve SV4. In this state, another switching valve is controlled to supply cleaning fluid L2 from the cleaning fluid supply unit 23 to the first flow path 251 and the third flow path 253. As a result, cleaning fluid L2 is supplied from the first flow path 251 to the liquid chamber 10A, and further from the third flow path 253 to the sealed space 21A.

[0180] Furthermore, the waste liquid L3 discharged from the sealed space 21A is discharged into the waste liquid tank 241 through the fourth flow path 254. As a result, the contaminant W1 adhering to the outer surface 102a can be mainly washed away.

[0181] Additionally, the cleaning fluid supply unit 23 may have a first supply unit for supplying cleaning fluid L2 and a second supply unit for supplying cleaning fluid L2 at a higher pressure than the first supply unit, and may be able to supply cleaning fluid L2 independently of the first and second supply units. By using a cleaning fluid supply unit with this configuration, cleaning fluid L2 can be supplied from the second supply unit to the first flow path 251, and cleaning fluid L2 can be supplied from the first supply unit to the third flow path 253.

[0182] The relatively high-pressure cleaning fluid L2 flows from the first flow path 251 through the liquid chamber 10A and the discharge port 102x into the sealing space 21A. As a result, the flow of cleaning fluid L2 from the sealing space 21A into the liquid chamber 10A is suppressed, and the problem of contaminants W1 on the outer surface 102a flowing into the liquid chamber 10A is also suppressed.

[0183] Furthermore, in the second cleaning, the cleaning fluid L2 can be supplied only to the third flow path 253 and not to the first flow path 251, and can flow only inside the sealed space 21A. Therefore, the outer surface 102a can be cleaned.

[0184] (Third cleaning (reverse cleaning of the drain hole))

[0185] Next, as Figure 6 As shown, the first flow path 251 and the fourth flow path 254 are closed by closing switching valves SV1 and SV8.

[0186] In this state, another switching valve is controlled to supply cleaning fluid L2 from cleaning fluid supply unit 23 to third flow path 253. Cleaning fluid L2 is supplied from third flow path 253 to sealing space 21A, and further supplied to liquid chamber 10A through discharge port 102x.

[0187] In addition, the waste liquid L3 discharged from the liquid chamber 10A is discharged into the waste liquid tank 241 through the second flow path 252.

[0188] As a result, the cleaning fluid L2 can flow from the outside of the liquid chamber 10A to the inside of the liquid chamber 10A to clean the liquid chamber 10A and the sealed space 21A. Due to the flow of the cleaning fluid L2, the contaminants W2 adhering to the inner surface 102b and the inside of the discharge hole 102x are lifted or stripped off.

[0189] (Fourth cleaning (circulating cleaning))

[0190] Next, as Figure 7 As shown, the fourth flow path 254 is closed by closing the switching valve SV8. In this state, another switching valve is controlled to supply cleaning fluid L2 from the cleaning fluid supply unit 23 to the first flow path 251 and the third flow path 253. As a result, cleaning fluid L2 is supplied from the first flow path 251 to the liquid chamber 10A, and further from the third flow path 253 to the sealed space 21A.

[0191] Furthermore, the waste liquid L3 ejected from the liquid chamber 10A is sprayed into the waste liquid tank 241 through the second flow path 252. As a result, contaminants W2 adhering to the inner surface 102b and inside the discharge port 102x can be primarily washed away.

[0192] In addition, by using a cleaning fluid supply unit having the first supply unit and the second supply unit described above as the cleaning fluid supply unit 23, the cleaning fluid L2 can be supplied from the first supply unit to the first flow path 251, and the cleaning fluid L2 can be supplied from the second supply unit to the third flow path 253.

[0193] The relatively high-pressure cleaning fluid L2 flows into the liquid chamber 10A from the third flow path 253 via the sealing space 21A and the discharge port 102x. As a result, the flow of cleaning fluid L2 from the liquid chamber 10A into the sealing space 21A is suppressed, and the problem of contaminants W2 on the inner surface 102b flowing into the sealing space 21A is also suppressed.

[0194] Furthermore, in the fourth cleaning, the cleaning fluid L2 can be supplied only to the first flow path 251 and not to the third flow path 253, and can flow only inside the liquid chamber 10A. Therefore, the inner surface 102b can be cleaned.

[0195] Next, as Figure 8 As shown, the first flow path 251 and the second flow path 252 are closed by respectively closing switching valves SV1 and SV4. In this state, by causing pressurized air to flow from the third flow path 253 to the fourth flow path 254, the cleaning fluid L2 stored in the third flow path 253, the sealed space 21A, and the fourth flow path 254 is discharged. The sprayed cleaning fluid L2 is sprayed into a waste liquid tank, for example, as waste liquid.

[0196] Furthermore, the cleaning fluid L2 in the liquid chamber 10A is replaced by the raw material fluid L1. The sprayed cleaning fluid L2 is sprayed into the waste fluid tank, for example, as waste fluid.

[0197] Through this operation, the cleaning of the discharge unit 10 is completed.

[0198] According to the droplet forming apparatus 1 constructed as described above, a droplet forming apparatus capable of efficiently and effectively cleaning nozzles can be provided.

[0199] In addition, in the droplet forming apparatus 1, when the type of raw material liquid to be discharged changes, or when a higher level of cleaning is required, such as after long-term operation, the discharge head 100 can be disassembled and cleaned.

[0200] Furthermore, in the droplet forming apparatus 1, when cleaning the discharge head 100, four cleaning processes from the first cleaning to the fourth cleaning are performed step by step, but the present invention is not limited thereto. In the droplet forming apparatus 1, at least one of the four cleaning processes from the first cleaning to the fourth cleaning can be performed independently, and the cleaning can be combined with another cleaning method, such as cleaning after disassembly.

[0201] For example, in the droplet forming apparatus 1, the outer surface 102a of the nozzle plate 102 can be cleaned separately, and then the interior of the liquid chamber 10A can be cleaned by sequentially performing the third and fourth cleanings described above.

[0202] Furthermore, in the droplet forming apparatus 1, the first cleaning and the second cleaning described above can be performed sequentially to clean the outer surface 102a of the nozzle plate 102. Then, for example, the interior of the liquid chamber 10A can be cleaned by disassembling and cleaning the droplet forming apparatus 1.

[0203] In this embodiment, when cleaning the discharge head 100, for example, during the first cleaning, the cleaning fluid L2 is supplied to the liquid chamber 10A from the first flow path 251, but the cleaning fluid L2 can also be supplied to the liquid chamber 10A from the second flow path 252. The supply direction of the cleaning fluid L2 can be appropriately controlled by operating the switching device 26.

[0204] In other words, the first flow path 251 and the second flow path 252 can be used interchangeably. Similarly, the third flow path 253 and the fourth flow path 254 can be used interchangeably. Specifically, when cleaning fluid L2 is supplied from the second flow path 252 to the liquid chamber 10A during the first cleaning, the third flow path 253 and the fourth flow path 254 can be interchanged, and the cleaning fluid L2 supplied to the sealed space 21A through the discharge port 102x can be ejected from the third flow path 253.

[0205] Similarly, in the second, third, and fourth cleaning processes, 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.

[0206] [Second Embodiment]

[0207] Figures 9 to 11 This is an explanatory diagram of the droplet forming apparatus and the microparticle manufacturing apparatus according to the second embodiment. In this embodiment, the same reference numerals will be used for the same components as in the first embodiment, and their detailed descriptions will be omitted.

[0208] <<Microparticle Manufacturing Device>>

[0209] Figure 9 This is a schematic diagram showing a microparticle manufacturing apparatus 500. The microparticle manufacturing apparatus 500 includes a droplet forming device 2, a chamber 510, a collection unit 520, a storage unit 530, and a control unit 550. In the microparticle manufacturing apparatus 500, microparticles are obtained by solidifying droplets D discharged from the droplet forming device 2.

[0210] The device used to solidify droplet D in the microparticle manufacturing apparatus 500 is not particularly limited, as long as droplet D can be solidified (become solid), and a known structure can be appropriately selected. For example, when droplet D contains a solid raw material and a volatile solvent, droplet D can be solidified by evaporating the solvent from droplet D.

[0211] There are no particular restrictions on the microparticles to be manufactured, but it is preferred that they comprise at least one substrate and a physiologically active substance, as well as other materials if necessary. The physiologically active substance can be any substance as long as it has some physiological activity in vivo, but in a preferred aspect, the physiologically active substance has the property of altering its physiological activity due to chemical or physical stimuli such as heating, cooling, shaking, stirring, and pH changes.

[0212] The droplet forming apparatus 2 is positioned above a cylindrical chamber 510 having an internal space, and discharges droplets D into the internal space of the chamber 510. The construction of the droplet forming apparatus 2 will be described later.

[0213] Chamber 510 is, for example, a cylindrical component with openings at the top and bottom. The droplet forming device 2 is inserted into the upper opening of chamber 510. The diameter of the lower part of chamber 510 gradually decreases downwards. The lower opening of chamber 510 converges near the central axis.

[0214] The pressure and temperature inside chamber 510 are managed, and the droplets D discharged from droplet forming device 2 are solidified. A descending airflow (conveyor airflow) is formed from above within chamber 510. The droplets D discharged from droplet forming device 2 are conveyed downwards by gravity and the conveyor airflow. The angle between the flow direction of the conveyor airflow and the direction in which droplets D are discharged from droplet forming device 2 is preferably within the range of 0 to 90 degrees. Here, "angle" is defined as the angle formed by the vectors of the "flow direction of the conveyor airflow" and the "direction in which droplets D are discharged from droplet forming device 2".

[0215] For example, when droplet D is conveyed by a transport gas stream, the solvent is removed from droplet D, and droplet D is solidified.

[0216] Solvent removal can be appropriately controlled by adjusting the temperature of the internal space of chamber 510, the pressure of the internal space, the temperature of the conveying gas flow, the type of gas in the conveying gas flow, and the type of solvent (vapor pressure).

[0217] After reaching the lower part of chamber 510, microparticles generated by the solidified droplets D are ejected from the lower opening of chamber 510.

[0218] Collection unit 520 collects the microparticles discharged from the lower part of chamber 510. Collection unit 520 can employ known constructions, such as a cyclone collector or a post-filter.

[0219] Storage unit 530 stores microparticles collected by collection unit 520.

[0220] The control unit 550 controls the operation of each component of the microparticle manufacturing apparatus 500. The control unit 550 can also be used as the control unit of the droplet forming apparatus 2.

[0221] It should be noted that solvent removal from droplet D does not necessarily have to be completed before it reaches the lower part of chamber 510, as long as the coalescence of droplet D can be suppressed. A configuration for additional drying of the microparticles collected by collection unit 520 can be provided, which will be described later.

[0222] <<Droplet Formation Device>>

[0223] Figure 10 and 11 This is an explanatory diagram of the droplet forming device 2. Figure 10 This is an overall view. Figure 11 This is a magnified view of the area near the discharge head.

[0224] like Figure 10 As shown, the droplet forming device 2 has a discharge unit 60 and a cleaning unit 70.

[0225] <Discharge Unit>

[0226] The discharge unit 60 discharges droplets of the aforementioned raw material liquid. The discharge unit 60 has a liquid chamber 60A for storing the raw material liquid and a discharge port 602x communicating with the liquid chamber 60A. The raw material liquid stored in the liquid chamber 60A is discharged through the discharge port 602x and forms spherical shapes in the gas phase due to the surface tension of the raw material liquid.

[0227] The discharge unit 60 has a discharge head 600 and a discharge unit body 610. The discharge head 600 has a liquid chamber 60A and a discharge hole 602x. The discharge head 600 is connected to the discharge unit body 610. The discharge unit 60 has a cylindrical shape, and the discharge head 600 is disposed at the lower end of the cylindrical body.

[0228] like Figure 11 As shown, the discharge head 600 has a head body 601, a nozzle plate 602, and a cover 603. The discharge head 600 can be disassembled into the head body 601, nozzle plate 602, and cover 603. Therefore, when the type of feed liquid to be discharged changes, or when a more advanced cleaning state is required, such as after long-term operation, the discharge head 600 can be disassembled and cleaned.

[0229] The head body 601 has a recess 60x corresponding to the liquid chamber 60A. The recess 60x is formed to extend in the circumferential direction of the head body 601.

[0230] The nozzle plate 602 has a plurality of discharge holes 602x. The nozzle plate 602 is a curved plate extending in the circumferential direction of the head body 601 and overlaps with the recess 601x to close the recess 601x, thereby forming part of the wall surface of the liquid chamber 60A. The plurality of discharge holes 602x are arranged along the extending direction of the nozzle plate 602.

[0231] In the discharge head 600, a plurality of discharge holes 602x are formed to be arranged in a circumferential direction along the side surface of the discharge head 600 (discharge unit 60).

[0232] The cover 603 presses the nozzle plate 602 against the head body 601 and keeps the contact surface between the head body 601 and the nozzle plate 602 impermeable to liquid.

[0233] The discharge unit body 610 has a connecting unit 611 connected to the discharge head 600 and a cylindrical unit 612 continuous with the connecting unit 611.

[0234] In the connecting unit 611, the discharge head 600 and the discharge unit body 610 are configured to be attached and detached at position 600A. The upper end of the discharge head 600 (the upper end of the head body 601) has a connecting unit 601a that connects to the discharge unit body 610.

[0235] For example, the connecting unit 601a has a diameter smaller than that of the head body 601 and is formed as a coaxial column (protruding shape). On the other hand, the connecting unit 611 of the discharge unit body 610 has a recess at its lower end for receiving the connecting unit 601a. ​​The connecting unit 601a and the connecting unit 611 employ, for example, a bayonet locking system and are easily attached and detached.

[0236] On the inner side of the cylindrical unit 612, a vibration unit 15 is provided to apply vibration to the raw material liquid stored in the liquid chamber 60A. The vibration unit 15 includes a vibrator 151 that generates vibration and an amplifying device 152 connected to the vibrator and amplifying the vibration. The vibration unit 15 is connected to the connecting unit 611 at the amplifying device 152.

[0237] Since the vibration unit 15 is located on the discharge unit body 610 side, when the discharge head 600 is removed from the discharge unit body 610, the discharge unit 60 does not need to disconnect the wiring connected to the vibration unit 15, making operation easy. Similarly, when the discharge head 600 is attached to the discharge unit body 610, the discharge unit 60 does not need to verify the electrical continuity of the wiring connected to the vibration unit 15, which is beneficial for operation.

[0238] Furthermore, since the vibration unit 15 is located on the discharge unit body 610 side, the discharge unit 60 does not require a structure such as connection terminals for removing and reconnecting the wiring connected to the vibration unit 15. Therefore, problems that would arise from such a structure, such as the vibration unit 15 malfunctioning due to poor contact caused by contaminants on the connection terminals, do not occur.

[0239] Furthermore, since the vibration unit 15 is located on the side of the discharge unit body 610, when the discharge head 600 is disassembled and cleaned, it is also possible to perform treatments that degrade the electrical wiring, such as ultrasonic cleaning when the discharge head 600 is immersed in cleaning solution, or sterilization treatment (e.g., autoclaving or boiling).

[0240] The vibrator 151 may adopt the same construction as the vibration unit used in the first embodiment.

[0241] Known horn-type resonant amplifiers can be used as amplifying devices 152. Examples of horn-type resonant amplifiers include each type of construction, such as stepped, exponential, and conical.

[0242] <Cleaning Unit>

[0243] like Figure 10 As shown, the cleaning unit 70 has a sealed space forming device 71 and a moving device 75.

[0244] The sealing space forming device 71 is a cylindrical member covering the side surface of the discharge head 600. The sealing space forming device 71 can liquid-tightly form a sealing space 71A communicating with the liquid chamber 60A through the discharge hole 602x outside the discharge unit 60. Furthermore, in Figure 10 In the diagram, the discharge head 600 and the sealing space forming device 71 are shown separately to make each component easier to see.

[0245] Specifically, the sealing space forming device 71 has a recess 71x facing the discharge head 600 and contacts the discharge head 600 from its side surface, while covering the discharge hole 602x. The recess 71x is continuous in the circumferential direction on the inner surface of the sealing space forming device 71. The space surrounded by the recess 71x and the side surface of the discharge head 600 is the sealing space 71A.

[0246] The sealing space forming device 71 can be moved in the vertical direction by a movable device 75 disposed above the sealing space forming device 71. Figure 9 The sealed space forming device 71 is shown in the retracted position. Figure 10 The state shown is such that the sealing space forming device 71 is lowered to cover the side surface of the discharge head 600 to form a sealing space 71A.

[0247] In this embodiment, the sealing space forming device 71 moves up and down, but the discharge unit 60 can be configured to move up and down, and the relative position between the discharge unit 60 and the sealing space forming device 71 can be changed.

[0248] Additionally, the cleaning unit 70 has the flow unit shown in the first embodiment. The flow unit includes a cleaning fluid supply unit 23, a waste liquid injection 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 device 26.

[0249] 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 configured to extend inside the cylindrical unit 612 and are respectively connected to the cleaning fluid supply unit 23 and the waste liquid injection unit 24 via the switching device 26.

[0250] The third flow path 253 and the fourth flow path 254 are connected to the sealed space 71A. The third flow path 253 and the fourth flow path 254 are configured to extend inside the cylindrical unit 612 and are connected to the cleaning fluid supply unit 23 and the waste liquid injection unit 24 via the switching device 26, respectively.

[0251] When the discharge head 600 is removed from the discharge unit body 610, the first flow path 251, the second flow path 252, the third flow path 253, and the fourth flow path 254 separate in the middle of each path. Furthermore, the first flow path 251, the second flow path 252, the third flow path 253, and the fourth flow path 254 connect the discharge head 600 to the discharge unit body 610; therefore, each flow path in the discharge head 600 and each flow path in the discharge unit body 610 are connected to each other.

[0252] Even in the droplet forming apparatus 2 with this configuration, when the raw material liquid is repeatedly discharged from the discharge port 602x, the solid components contained in the raw material liquid L1 may partially precipitate on the outer wall of the liquid chamber 60A (outer surface of the nozzle plate 602) and the inner wall of the liquid chamber 60A (inner surface of the nozzle plate 102), and contaminants may adhere.

[0253] In the droplet forming apparatus 2, the cleaning unit 70 can be used to easily clean the contaminants from the discharge unit 60. The method of cleaning the discharge unit 60 using the cleaning unit 70 is the same as the method of cleaning the discharge unit 10 using the cleaning unit 20 of the first embodiment.

[0254] According to the droplet forming apparatus 2 constructed as described above, a droplet forming apparatus capable of efficiently and effectively cleaning nozzles can be provided.

[0255] Furthermore, according to the microparticle manufacturing apparatus 500 constructed as described above, a droplet forming apparatus 2 is provided, and high-quality microparticles can be manufactured.

[0256] Although suitable embodiments of the invention have been described above with reference to the accompanying drawings, the invention is not limited to these examples. The various shapes or combinations of 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 invention.

[0257] [Example]

[0258] The invention will be described below based on examples, but the invention is not limited to the following examples.

[0259] In each example and comparative example, the following raw material solutions were used for evaluation.

[0260] Metformin hydrochloride (manufactured by Tokyo Chemical Industry Co., Ltd.) was pulverized using a ball mill to a volume average particle size of 1.5 μm.

[0261] Eight parts by weight of pulverized metformin hydrochloride, 12 parts by weight of lactic acid / glycolic acid copolymer (product name: PLGA-7510, manufactured by Wako Pure Chemical Industries, Ltd.), and 80 parts by weight 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 the raw material solution.

[0262] Because metformin hydrochloride is insoluble in acetone, the obtained raw material solution is a dispersion of metformin hydrochloride.

[0263] <Example 1>

[0264] The droplet forming apparatus and microparticle manufacturing apparatus described in the second embodiment were prepared. The volume of the liquid chamber is 150 mm³. 3 The volume of the sealed space is 1000 mm. 3 .

[0265] The droplet forming apparatus according to Example 1 is evaluated through the following procedure.

[0266] ((1) Drain before cleaning)

[0267] The nozzle plate was fabricated using a nickel plate with a length of 42.5 mm, a width of 6.8 mm, and a thickness of 20 μm. Multiple discharge holes with a diameter of 35 μm were formed in the nickel plate by electroforming. The distance between the discharge holes was set to 200 μm.

[0268] The feed liquid is injected into the liquid chamber, and droplets are discharged by applying a pressure of 0.1 MPa to the discharge port of the feed liquid in the liquid chamber while simultaneously applying vibration at 70 kHz from the vibration unit. The pressure applied to the discharge port is measured by a pressure measuring instrument (AP-13S, manufactured by Keyence Corporation) installed in the first flow path relatively close to the discharge port. The pressure measuring instrument is installed as close as possible to the discharge port in the first flow path.

[0269] The chamber is cylindrical, with a diameter of 800 mm and a height of 1540 mm. The droplet forming device is inserted into the chamber from the top, and the discharge head is located 50 to 100 mm below the top of the chamber. Room temperature air is used as the conveying airflow at a speed of 1000 m... 3 The droplets flow from the periphery of the droplet forming device to the lower part of the chamber at a rate of / min.

[0270] The raw material liquid is discharged from the droplet forming device, and the microparticles solidified in the chamber are collected by a cyclone collector installed at the bottom of the chamber to obtain particles before washing.

[0271] (2) Cleaning)

[0272] The cleaning unit is used to clean the discharge head every 20 minutes. Clean according to the following procedure.

[0273] (Clean the drain head)

[0274] During cleaning, firstly, after stopping the discharge of droplets from the droplet forming device, the side surface of the discharge head is covered by a sealing space forming device to form a sealed space. Acetone is used as the cleaning fluid.

[0275] First, cleaning fluid is supplied to the liquid chamber through the first flow path, and the cleaning fluid flows from the liquid chamber to the sealed space through the discharge hole, and is ejected from the fourth flow path. The pressure of the cleaning fluid supplied from the first flow path is set to 0.15 MPa, and the liquid supply time of the cleaning fluid is set to 15 seconds (first cleaning, discharge hole cleaning).

[0276] Next, the cleaning fluid is supplied to the sealed space through the third flow path and ejected through the fourth flow path. The pressure of the cleaning fluid supplied through the third flow path is set to 0.15 MPa, and the liquid supply time is set to 5 seconds (second cleaning, outer surface cleaning). During the liquid supply, approximately 50 to 100 ml of cleaning fluid flows.

[0277] Next, the cleaning fluid is supplied to the sealed space through the third flow path, and flows from the sealed space to the liquid chamber through the discharge port, and is ejected from the second flow path. The pressure of the cleaning fluid supplied from the third flow path is set to 0.15 MPa, and the liquid supply time of the cleaning fluid is set to 15 seconds (third cleaning, reverse cleaning through the discharge port).

[0278] Next, the cleaning fluid is supplied to the sealed space from the first flow path and ejected from the second flow path. The pressure of the cleaning fluid supplied from the first flow path is set to 0.15 MPa, and the liquid supply time is set to 15 seconds (fourth cleaning, circulating cleaning). During the liquid supply, approximately 50 to 100 ml of cleaning fluid flows.

[0279] Next, the cleaning fluid in the liquid chamber is replaced with the raw material solution, and the sealed space is retracted to form the device to complete the cleaning.

[0280] (3) The state of the drain hole after cleaning)

[0281] After cleaning, assess the condition of the discharge orifice (nozzle) using the following method.

[0282] (4) Drain after cleaning)

[0283] After cleaning, the raw material liquid was discharged under the same conditions as before cleaning ((1)) to obtain the cleaned particles of Example 1. Furthermore, the recovery rate of the discharge pores (recovery rate after discharge) was evaluated using the following method.

[0284] (Examples 2 to 6, comparative examples)

[0285] Examples 2 through 6 and the comparative examples were performed in the same manner as Example 1, except that the conditions (cleaning of the discharge head) were changed to those shown in Table 1.

[0286] Furthermore, in the comparative example, the same devices as in Examples 1 to 6 were used, but not all cleaning was performed. Therefore, the results of the comparative example are considered to be the same as those of the construction without the cleaning unit.

[0287] (Measurement of average particle size distribution)

[0288] The average particle size distribution of the particles obtained in Examples 1 to 6 and Comparative Example ((4) after washing and discharge) was measured by the following method.

[0289] -Particle Diameter Measurement Methods-

[0290] The measurement method using a flow particle image analyzer will be described below. The measurement device used is the Sysmex FPIA-3000 flow particle image analyzer.

[0291] The measurements are performed according to the following procedures (1) to (3).

[0292] (1) The water used for measurement is passed through a filter to remove fine dust, and 10 -3 cm 3 Water with 20 or fewer particles within the measurement range (equivalent circle diameter of 0.60 micrometers or more and less than 159.21 micrometers).

[0293] (2) Add a few drops of nonionic surfactant (preferably Contaminon N manufactured by Wako Pure Chemical Industries, Ltd.) to 10 ml of water, then add 5 mg of the measurement sample, and use an ultrasonic disperser UH-50 manufactured by STM at 20 kHz and 50 W / 10 cm⁻¹. 3 Dispersion processing was carried out for 1 minute under the specified conditions.

[0294] (3) Then, a total of 5 minutes of dispersion treatment was performed, and the particle concentration of the sample was measured to be 4000 to 8000 particles / 10. -3 cm3 For a sample dispersion (for particles within the range of equivalent circular diameters used for measurement), the particle size distribution of particles with an equivalent circular diameter of 0.60 μm or greater and less than 159.21 μm is measured.

[0295] The sample dispersion flows through a flat, uniform, and transparent flow cell (approximately 200 micrometers thick) along the flow direction. A flash lamp and a CCD camera are mounted on the flow cell, positioned opposite each other to form an optical path through the thickness of the flow cell. As the sample dispersion flows, the flash lamp is shone at 1 / 30-second intervals to obtain images of the particles flowing through the flow cell. As a result, each particle is captured as a two-dimensional image with a constant area parallel to the flow cell. Based on the area of ​​the two-dimensional image of each particle, the diameter of a circle with the same area is calculated as the equivalent circle diameter.

[0296] The equivalent circular diameter of 1200 or more particles can be measured in approximately one minute, and the number of particles with a specific equivalent circular diameter and the percentage (number %) are measured based on the distribution of equivalent circular diameters. Results are obtained (calculated as frequency % and cumulative %) by dividing the range from 0.06 to 400 micrometers into 226 channels (30 channels per octave). In practical measurements, particles are measured within the range of equivalent circular diameters of 0.60 micrometers or larger and less than 159.21 micrometers.

[0297] Obtain the volume average particle size (Dv) and number average particle size (Dn), and calculate Dv / Dn as the average particle size distribution.

[0298] Table 1 shows the evaluation results.

[0299] Each column in Table 1 describes a four-level assessment of A, B, C, and D, with A, B, and C rated as good and D rated as poor. Furthermore, Table 2 shows the assessment criteria described in Table 1.

[0300] Each evaluation described in Table 1 was performed by photographing the surface of the drain hole after cleaning under each condition, and by magnifying and visually verifying the obtained images. Specifically, an image of an area of ​​approximately 2mm × 1.5mm on the surface of the drain hole was photographed, and the photographed image was magnified and displayed on the entire screen of a 19-inch monitor (screen aspect ratio 4:3) for verification. Based on the ratio of the captured image to the diagonal length of the monitor (2.5mm:482.6mm), the magnification can be calculated as 193x. The definitions for each evaluation are as follows.

[0301] (State of the drain hole after cleaning)

[0302] In ((3) the state of the drain holes after cleaning), the number of drain holes with residual contaminants was counted in the captured images. When "contaminants" remained, solid material presumably metformin hydrochloride was observed clogging the nozzle holes or adhering to the nozzle surface. The ratio of the number of drain holes with residual contaminants (B) to the total number of drain holes (A) was obtained as a percentage (B / A×100%).

[0303] (Recovery rate after excretion)

[0304] In ((4) Discharge after cleaning), the raw material liquid is discharged from the discharge hole after cleaning, and the ratio of the number of discharge holes (C) that are normally discharged to the total number of discharge holes (A) is obtained as a percentage (C / A×100%).

[0305] "Normal discharge" refers to the operation of discharging a droplet in which the droplet is discharged from the discharge hole in a direction perpendicular to the nozzle plate.

[0306] Therefore, when (i) no discharge is performed, (ii) the raw material liquid drips from the discharge hole along the surface of the nozzle plate, (iii) the droplet is discharged in a curve rather than perpendicular to the nozzle plate, and (iv) multiple droplets are discharged from the discharge hole, the operation of discharging a single droplet is evaluated as "abnormal discharge".

[0307] (Average particle size distribution)

[0308] The average particle size distribution of the particles obtained after ((4) washing and discharge) was measured.

[0309] (Results after cleaning)

[0310] The lowest evaluation results are shown for the three evaluation items: the state of the discharge pore after cleaning, the recovery rate after discharge, and the average particle size distribution.

[0311] [Table 1]

[0312]

[0313] [Table 2]

[0314]

[0315] In any of Examples 1 to 6, the effect of using the sealed space forming unit to clean the discharge head was observed, and the condition of the discharge orifice was good after cleaning. Furthermore, it was found that the formed particles had a small particle size distribution and minimal particle size variation.

[0316] On the other hand, in the comparative example where cleaning was not performed using the sealed space forming unit, a large amount of contaminants adhered to the discharge port and its vicinity when the device was used. Furthermore, in the comparative example, the particle size distribution was affected by contaminant adhesion, and the variation was greater than in Examples 1 to 6.

[0317] The above results confirm that the present invention is useful.

[0318] The present invention includes the following aspects.

[0319] [1] A droplet forming apparatus includes: a liquid chamber; a discharge orifice configured to discharge a raw material liquid in the liquid chamber in the form of a droplet; a sealing space forming device; and at least two flow paths, wherein the sealing space forming device is capable of forming a sealing space on the side opposite to the liquid chamber of the discharge orifice, communicating with the liquid chamber through the discharge orifice, and the at least two flow paths are communicating with each other through the sealing space.

[0320] [2] According to the droplet forming apparatus of [1], the interior of the liquid chamber, the discharge port and the sealed space are washable by allowing the cleaning fluid to flow into the liquid chamber and the sealed space.

[0321] [3] The droplet forming apparatus according to [2] further includes: a cleaning fluid supply unit configured to supply cleaning fluid; and a waste liquid injection unit configured to inject waste liquid generated through the interior of the cleaning fluid chamber, the discharge port and the sealed space, wherein the at least two flow paths include a first flow path and a second flow path connected to the fluid chamber and configured to be openable and closable, and a third flow path and a fourth flow path configured to be openable and closable at a location accessible to the sealed space, the first flow path and the second flow path being connected to the cleaning fluid supply unit and the waste liquid injection unit, and the third flow path and the fourth flow path being connected to the cleaning fluid supply unit and the waste liquid injection unit.

[0322] [4] The droplet forming apparatus according to [3] further includes: a control unit configured to control at least the cleaning fluid supply unit and the waste liquid injection unit, wherein the control unit performs a first cleaning in which the second flow path and the third flow path are closed, the cleaning fluid is supplied to the sealed space from the first flow path through the liquid chamber, and the waste liquid is injected into the sealed space from the fourth flow path.

[0323] [5] The droplet forming apparatus according to [3] or [4] further includes: a control unit configured to control at least the cleaning fluid supply unit and the waste liquid spraying unit, wherein the control unit performs a second cleaning in which a second flow path is closed, the cleaning fluid is supplied to the sealed space from one of the third flow path and the fourth flow path, and the waste liquid in the sealed space is sprayed from the other of the third flow path and the fourth flow path.

[0324] [6] According to the droplet forming apparatus of [5], the cleaning fluid supply unit includes a first supply unit for supplying cleaning fluid and a second supply unit for supplying cleaning fluid at a higher pressure than the first supply unit, and in the second cleaning, the cleaning fluid is supplied from the second supply unit to a first flow path, and the cleaning fluid is supplied from the first supply unit to one of a third flow path and a fourth flow path.

[0325] [7] The droplet forming apparatus according to any one of [3] to [6] further includes: a control unit configured to control at least the cleaning fluid supply unit and the waste liquid injection unit, wherein the control unit performs a third cleaning, in which the first flow path and the fourth flow path are closed, the cleaning fluid is supplied from the third flow path to the liquid chamber through the sealed space, and the waste liquid in the liquid chamber is injected from the second flow path.

[0326] [8] The droplet forming apparatus according to any one of [3] to [7] further includes: a control unit configured to control at least the cleaning fluid supply unit and the waste liquid spraying unit, wherein the control unit performs a fourth cleaning, in which a fourth flow path is closed, the cleaning fluid 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 sprayed from the other of the first flow path and the second flow path.

[0327] [9] According to the droplet forming apparatus of [8], wherein the cleaning fluid supply unit includes a first supply unit for supplying cleaning fluid and a second supply unit for supplying cleaning fluid at a higher pressure than the first supply unit, and in the fourth cleaning, the cleaning fluid is supplied from the second supply unit to the third flow path, and the cleaning fluid is supplied from the first supply unit to one of the first flow path and the second flow path.

[0328]

[10] The droplet forming apparatus according to any one of [3] to [9], wherein the cleaning fluid supply unit and the raw material supply unit for supplying raw material liquid are switchably connected to the first flow path.

[0329]

[11] The droplet forming apparatus according to any one of [1] to

[10] further includes: a discharge head having a liquid chamber and a discharge orifice; and a discharge unit body to which the discharge head is connected, wherein the discharge head and the discharge unit body are configured to be attachable and detachable.

[0330]

[12] According to the droplet forming apparatus of

[11] , the discharge head includes a head body having the liquid chamber and a nozzle plate forming a portion of the wall surface of the liquid chamber and having a discharge hole, and the discharge head is detachable from the head body and the nozzle plate.

[0331]

[13] According to the droplet forming apparatus of

[11] or

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

[0332]

[14] According to the droplet forming apparatus of

[13] , the vibration unit includes a vibrator that generates vibration and an amplifying device connected to the vibrator and amplifying the vibration.

[0333]

[15] A microparticle manufacturing apparatus includes: a droplet forming apparatus according to any one of [1] to

[14] ; and a curing device configured to cure droplets discharged from the droplet forming apparatus.

[0334] In addition, the present invention also includes the following aspects.

[0335] [1-1] A droplet forming apparatus, comprising:

[0336] The discharge head has a liquid chamber, a discharge orifice for discharging the raw material liquid in the liquid chamber in the form of droplets, and at least two flow paths;

[0337] The sealed space forms the device;

[0338] A cleaning fluid supply unit, configured to supply cleaning fluid;

[0339] A waste liquid injection unit is configured to inject waste liquid generated through a cleaning liquid chamber, a discharge port, and a sealed space; and

[0340] The control unit is configured to control at least the cleaning fluid supply unit and the waste fluid injection unit, wherein

[0341] The sealing space forming device can form a sealing space on the side opposite to the liquid chamber of the discharge port, which communicates with the liquid chamber through the discharge port.

[0342] At least two flow paths include

[0343] A first flow path and a second flow path, which are connected to the liquid chamber and configured to be openable and closable, and

[0344] The third and fourth flow paths are configured to be openable and closable at locations accessible to a sealed space.

[0345] At least two flow paths are connected to each other through a sealed space.

[0346] The first flow path and the second flow path are connected to the cleaning fluid supply unit and the waste liquid injection unit.

[0347] The third and fourth flow paths connect to the cleaning fluid supply unit and the waste liquid injection unit.

[0348] The cleaning fluid flows through the liquid chamber and the sealed space, thereby cleaning the interior of the liquid chamber, the drain hole, and the sealed space.

[0349] Control unit performs

[0350] In the first cleaning, the second and third flow paths are closed. Cleaning fluid is supplied from the first flow path through the liquid chamber to the sealed space, and waste fluid in the sealed space is ejected from the fourth flow path.

[0351] In the second cleaning, the second flow path is closed, cleaning fluid is supplied to the sealed space from one of the third and fourth flow paths, and waste fluid in the sealed space is ejected from the other of the third and fourth flow paths.

[0352] [1-2] According to the droplet forming apparatus of [1-1], the cleaning fluid supply unit includes a first supply unit for supplying cleaning fluid and a second supply unit for supplying cleaning fluid at a higher pressure than the first supply unit, and in the second cleaning, the cleaning fluid is supplied from the second supply unit to a first flow path, and the cleaning fluid is supplied from the first supply unit to one of a third flow path and a fourth flow path.

[0353] [1-3] According to the droplet forming apparatus of [1-2], the cleaning fluid supply unit and the raw material supply unit for supplying raw material liquid are switchably connected to the first flow path.

[0354] [2-1] A droplet forming apparatus, comprising:

[0355] The discharge head has a liquid chamber, a discharge orifice for discharging the raw material liquid in the liquid chamber in the form of droplets, and at least two flow paths;

[0356] The sealed space forms the device;

[0357] A cleaning fluid supply unit, configured to supply cleaning fluid;

[0358] A waste liquid injection unit is configured to inject waste liquid generated through a cleaning liquid chamber, a discharge port, and a sealed space; and

[0359] The control unit is configured to control at least the cleaning fluid supply unit and the waste fluid injection unit, wherein

[0360] The sealing space forming device can form a sealing space on the side opposite to the liquid chamber of the discharge port, which communicates with the liquid chamber through the discharge port.

[0361] At least two flow paths include

[0362] A first flow path and a second flow path, which are connected to the liquid chamber and configured to be openable and closable, and

[0363] The third and fourth flow paths are configured to be openable and closable at locations accessible to a sealed space.

[0364] At least two flow paths are connected to each other through a sealed space.

[0365] The first flow path and the second flow path are connected to the cleaning fluid supply unit and the waste liquid injection unit.

[0366] The third and fourth flow paths connect to the cleaning fluid supply unit and the waste liquid injection unit.

[0367] The cleaning fluid is allowed to flow through the liquid chamber and the sealed space to clean the interior of the liquid chamber, the drain port, and the sealed space.

[0368] This control is performed.

[0369] In the third cleaning, the first and fourth flow paths are closed. Cleaning fluid is supplied from the third flow path through the liquid chamber to the sealed space, and waste fluid in the sealed space is ejected from the second flow path.

[0370] In the fourth cleaning, the fourth flow path is closed, cleaning fluid is supplied to the liquid chamber from one of the first and second flow paths, and waste liquid in the liquid chamber is ejected from the other of the first and second flow paths.

[0371] [2-2] According to the droplet forming apparatus of [2-1], the cleaning fluid supply unit includes a first supply unit for supplying cleaning fluid and a second supply unit for supplying cleaning fluid at a higher pressure than the first supply unit, and in the fourth cleaning, the cleaning fluid is supplied from the second supply unit to a third flow path, and the cleaning fluid is supplied from the first supply unit to one of the first flow path and the second flow path.

[0372] [2-3] According to the droplet forming apparatus of [2-2], the cleaning fluid supply unit and the raw material supply unit for supplying raw material liquid are switchably connected to the first flow path.

[0373] [3-1] A droplet forming apparatus, comprising:

[0374] The discharge head has a liquid chamber, a discharge orifice for discharging the raw material liquid in the liquid chamber in the form of droplets, and at least two flow paths;

[0375] The sealed space forms the device;

[0376] A cleaning fluid supply unit, configured to supply cleaning fluid;

[0377] A waste liquid injection unit is configured to inject waste liquid generated through a cleaning liquid chamber, a discharge port, and a sealed space; and

[0378] The control unit is configured to control at least the cleaning fluid supply unit and the waste fluid injection unit, wherein

[0379] The sealing space forming device can form a sealing space on the side opposite to the liquid chamber of the discharge port, which communicates with the liquid chamber through the discharge port.

[0380] At least two flow paths include

[0381] A first flow path and a second flow path, which are connected to the liquid chamber and configured to be openable and closable, and

[0382] The third and fourth flow paths are configured to be openable and closable at locations accessible to a sealed space.

[0383] At least two flow paths are connected to each other through a sealed space.

[0384] The first flow path and the second flow path are connected to the cleaning fluid supply unit and the waste liquid injection unit.

[0385] The third and fourth flow paths connect to the cleaning fluid supply unit and the waste liquid injection unit.

[0386] The cleaning fluid is allowed to flow through the liquid chamber and the sealed space to clean the interior of the liquid chamber, the drain port, and the sealed space.

[0387] Control unit performs

[0388] In the first cleaning, the second and third flow paths are closed. Cleaning fluid is supplied from the first flow path through the liquid chamber to the sealed space, and waste fluid in the sealed space is ejected from the fourth flow path.

[0389] In the second cleaning, the second flow path is closed, cleaning fluid is supplied to the sealed space from one of the third and fourth flow paths, and waste fluid in the sealed space is ejected from the other of the third and fourth flow paths.

[0390] In the third cleaning, the first and fourth flow paths are closed. Cleaning fluid is supplied from the third flow path through a sealed space to the liquid chamber, and waste liquid in the liquid chamber is ejected from the second flow path.

[0391] In the fourth cleaning, the fourth flow path is closed, cleaning fluid is supplied to the liquid chamber from one of the first and second flow paths, and waste liquid in the liquid chamber is ejected from the other of the first and second flow paths.

[0392] [List of reference numerals]

[0393] 1, 2: Droplet forming apparatus

[0394] 10, 60: Discharge unit

[0395] 10A, 60A: liquid chamber

[0396] 15: Vibration Unit

[0397] 20, 70: Cleaning Unit

[0398] 21, 71: Sealed space forming device

[0399] 21A, 71A: Sealed space

[0400] 22: Flow unit

[0401] 23: Cleaning fluid supply unit

[0402] 24: Waste liquid injection unit

[0403] 50, 550: Control Unit

[0404] 100, 600: Discharge head

[0405] 101, 601: Head Body

[0406] 102, 602: Nozzle plate

[0407] 102x, 602x: Discharge port

[0408] 110, 610: Discharge unit main body

[0409] 151: Vibrator

[0410] 152: Amplifying devices

[0411] 191: Raw material liquid tank

[0412] 231: Cleaning fluid tank

[0413] 251: First flow path

[0414] 252: Second flow path

[0415] 253: Third Flow Path

[0416] 254: Fourth Flow Path

[0417] 500: Microparticle Manufacturing Device

[0418] D: Droplet

[0419] L1: Raw material liquid

[0420] L2: Cleaning fluid

[0421] L3: Waste liquid

[0422] [List of Citations]

[0423] [Patent Documents]

[0424] [Patent Document 1]

[0425] Japanese unexamined patent application, first publication number 2015-027657.

Claims

1. A droplet formation device comprising: a liquid chamber; a nozzle plate including a discharge hole configured to discharge a raw liquid in the liquid chamber in the form of a droplet, the liquid chamber extending in a direction parallel to a surface of the nozzle plate; a seal space forming means; and at least two flow paths, wherein the seal space forming means is capable of forming a seal space in communication with the liquid chamber through the discharge hole on a side opposite to the liquid chamber with respect to the nozzle plate, and the at least two flow paths include a through hole formed on the same side as the liquid chamber with respect to the nozzle plate and a pipe connected to the liquid chamber, and are in communication with each other through the seal space, the at least two flow paths include: a first flow path and a second flow path connected to the liquid chamber from both ends thereof in a direction perpendicular to the surface of the nozzle plate, respectively, and a third flow path and a fourth flow path provided to the seal space from both ends thereof in a direction perpendicular to the surface of the nozzle plate, respectively.

2. The droplet formation device according to claim 1, wherein an inside of the liquid chamber, the discharge hole, and the seal space is capable of being washed by causing a washing liquid to flow to the liquid chamber and the seal space.

3. The droplet formation device according to claim 2, further comprising: a washing liquid supply unit configured to supply a washing liquid; and a waste liquid injection unit configured to inject a waste liquid generated by washing the inside of the liquid chamber, the discharge hole, and the seal space, wherein the first flow path and the second flow path are connected to the washing liquid supply unit and the waste liquid injection unit, and the third flow path and the fourth flow path are connected to the washing liquid supply unit and the waste liquid injection unit.

4. The droplet formation device according to claim 3, further comprising: a control unit configured to control at least the washing liquid supply unit and the waste liquid injection unit, wherein the control unit performs a first washing in which the second flow path and the third flow path are closed, the washing liquid is supplied from the first flow path to the seal space through the liquid chamber, and the waste liquid is injected from the fourth flow path to the seal space.

5. The droplet formation device according to claim 3 or 4, further comprising: a control unit configured to control at least the washing liquid supply unit and the waste liquid injection unit, wherein the control unit performs a second washing in which the second flow path is closed, the washing liquid is supplied from one of the third flow path and the fourth flow path to the seal space, and the waste liquid in the seal space is injected from the other of the third flow path and the fourth flow path.

6. The droplet formation device according to claim 5, wherein the washing liquid supply unit includes a first supply unit that supplies a washing liquid, and a second supply unit that supplies a washing liquid at a higher pressure than the first supply unit, and the control unit is configured to control the first supply unit and the second supply unit. 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. The droplet formation apparatus according to any one of claims 3 to 6, further comprising: a control unit configured to control at least the cleaning liquid supply unit and the waste liquid ejection unit, wherein the control unit performs 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 to the liquid chamber through the sealed space, and the waste liquid in the liquid chamber is ejected from the second flow path.

8. The droplet formation apparatus according to any one of claims 3 to 7, further comprising: a control unit configured to control at least the cleaning liquid supply unit and the waste liquid ejection unit, wherein the control unit performs a fourth cleaning in which the fourth flow path is closed, the cleaning liquid is supplied from one of the first flow path and the second flow path to the liquid chamber, and the waste liquid in the liquid chamber is ejected from the other of the first flow path and the second flow path.

9. The droplet formation apparatus according to claim 8, wherein the cleaning liquid supply unit includes 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.

10. The droplet formation apparatus according to any one of claims 3 to 9, wherein the cleaning liquid supply unit and a raw material liquid supply unit that supplies a raw material liquid are switchably connected to the first flow path.

11. The droplet formation apparatus according to any one of claims 1 to 10, further comprising: a discharge head having a liquid chamber and a discharge hole; and a discharge unit body to which the discharge head is connected, wherein the discharge head and the discharge unit body are configured to be attachable and detachable.

12. The droplet formation apparatus according to claim 11, wherein the discharge head includes a head body provided with the liquid chamber, the nozzle plate forms a part of a wall surface of the liquid chamber, and the discharge head is detachable into the head body and the nozzle plate.

13. The droplet formation apparatus according to claim 11 or 12, wherein the discharge unit body has a vibration unit that applies vibration to a raw material liquid stored in the liquid chamber.

14. The droplet formation apparatus according to claim 13, wherein the vibration unit includes a vibrator that generates vibration, and an amplification device connected to the vibrator and amplifying the vibration.

15. A fine particle production apparatus comprising: the droplet formation apparatus according to any one of claims 1 to 14; and a solidification device configured to solidify a droplet discharged from the droplet formation apparatus.

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