JP2022074789A - Droplet forming apparatus and fine particle manufacturing apparatus - Google Patents

Abstract

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

Description

The present invention relates to a droplet forming apparatus and a fine particle producing apparatus.

The fine particles having a narrow particle size distribution are used for various purposes such as toner fine particles for electrophotographic, spacer particles for liquid crystal panels, carriers of physiologically active substances such as pharmaceutical compounds, and the like. Among these, as an apparatus for producing toner fine particles, a manufacturing apparatus for ejecting a liquid toner material as droplets and granulating the particles as fine particles having a desired particle size is known (see, for example, Patent Document 1). In the manufacturing apparatus described in Patent Document 1, a raw material liquid containing a material for fine particles is discharged as droplets from a nozzle, and a solvent is removed from the droplets to produce fine particles having a desired particle size distribution.

In the above-mentioned Patent Document 1, a configuration example in which a plurality of nozzles are arranged in a vertical direction (gravity direction) and a material is discharged is shown. Arranging a plurality of nozzles in this way is expected to improve productivity.

On the other hand, it is known that when the raw material liquid is discharged from the nozzle, dirt derived from the fine particle material adheres to the periphery of the nozzle. Since such dirt affects the size of the droplets ejected from the nozzle and the production efficiency, countermeasures are required.

The present invention has been made in view of such circumstances, and an object of the present invention is to provide a droplet forming apparatus which is not easily affected by dirt adhering to the periphery of a nozzle. Another object of the present invention is to provide a fine particle manufacturing apparatus provided with the above-mentioned droplet forming apparatus and capable of stable production of high-quality fine particles.

The inventors think that when the raw material liquid is discharged from the nozzle, if the raw material liquid adheres to the periphery of the nozzle and causes stains, the influence of the stains can be suppressed by providing the nozzle at a position where the stains are unlikely to occur. , The present invention has been completed.

That is, in order to solve the above-mentioned problems, one aspect of the present invention has a discharge head for discharging droplets of a raw material liquid, the discharge head has a plurality of discharge holes, and the plurality of discharge holes have a plurality of discharge holes. A droplet forming apparatus is formed on the side surface of the discharge head, and each of the plurality of discharge holes is provided at a position on the side surface that does not overlap with a virtual range where the raw material liquid is assumed to drip from the discharge holes. offer.

According to the present invention, it is possible to provide a droplet forming apparatus that is not easily affected by dirt adhering to the periphery of the nozzle. It is possible to provide a fine particle manufacturing apparatus provided with the above-mentioned droplet forming apparatus and capable of stable production of high-quality fine particles.

FIG. 1 is a schematic view showing a fine particle manufacturing apparatus 500. FIG. 2 is a partially enlarged view of the discharge portion. FIG. 3 is an enlarged view illustrating the arrangement of the discharge holes 102x. FIG. 4 is a schematic view showing a state around the discharge hole 102x on the side surface 100a.

Hereinafter, the droplet forming apparatus and the fine particle producing apparatus according to the present embodiment will be described with reference to FIGS. 1 to 4. In all the drawings below, the dimensions and ratios of the components are appropriately different in order to make the drawings easier to see.

In the following description, the xyz orthogonal coordinate system is set, and the positional relationship of each member will be described with reference to this xyz orthogonal coordinate system. Here, a predetermined direction in the horizontal plane is the x-axis direction, a direction orthogonal to the x-axis direction in the horizontal plane is the y-axis direction, and a direction orthogonal to each of the x-axis direction and the y-axis direction (that is, the vertical direction) is the z-axis direction. And.

In the following description, the + z direction may be referred to as "up" and "upward", and the -z direction may be referred to as "down" and "downward". "Upper" is the + z side of the structure, "upper" is the + z side of the structure, "lower" is the -z side of the structure, and "lower" is the -z side of the structure. Means.

FIG. 1 is a schematic view showing a fine particle manufacturing apparatus 500. The fine particle manufacturing apparatus 500 includes a droplet forming apparatus 1, a chamber 510, a collecting unit 520, a storage unit 530, and a control unit 550. In the fine particle manufacturing apparatus 500, fine particles are obtained by solidifying the droplet D discharged from the droplet forming apparatus 1.

The means for solidifying the droplet D in the fine particle manufacturing apparatus 500 is not particularly limited as long as the droplet D can be solidified (solid state), and a known configuration can be appropriately selected. For example, when the droplet D contains a solid raw material and a volatile solvent, the droplet D can be solidified by volatilizing the solvent from the droplet D.

The fine particles produced are not particularly limited, but preferably contain at least one kind of base material and a physiologically active substance having physiological activity, and if necessary, include other materials. The bioactive substance may be any bioactive substance as long as it has some bioactivity, but in a preferred embodiment, a chemical or physical stimulus such as heating, cooling, shaking, stirring, or pH change is used. It has the property of changing its physiological activity.

The droplet forming device 1 is provided on the upper part of the cylindrical chamber 510 having an internal space, and ejects the droplet D into the internal space of the chamber 510. The configuration of the droplet forming apparatus 1 will be described later.

Chamber 510 is, for example, a cylindrical member with an open top and bottom. The droplet forming device 1 is inserted into the opening at the upper part of the chamber 510. The diameter of the lower part of the chamber 510 gradually decreases toward the lower side. The lower opening of chamber 510 converges near the central axis.

In the chamber 510, the pressure and temperature of the internal space are controlled, and the droplet D discharged from the droplet forming device 1 is solidified. In the chamber 510, a downdraft (conveyed airflow) is formed from above. The droplet D ejected from the droplet forming device 1 is conveyed downward by gravity and a transport air flow. The flow direction of the conveyed airflow is preferably a direction substantially perpendicular to the direction in which the droplet D is discharged from the droplet forming device 1.

For example, the solvent is removed from the droplet D while being transported by the transport airflow, and the droplet D is solidified.

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

The fine particles formed by solidifying the droplet D reach the lower part of the chamber 510 and then are discharged from the opening at the lower part of the chamber 510.

The collecting unit 520 collects the fine particles discharged from the lower part of the chamber 510. The collection unit 520 can adopt a known configuration such as a cyclone collection and a back filter.

The storage unit 530 stores the fine particles collected by the collection unit 520.

The control unit 550 controls the operation of each configuration of the fine particle manufacturing apparatus 500. The control unit 550 may also serve as the control unit of the droplet forming device 1.

It should be noted that the removal of the solvent from the droplet D does not necessarily have to be completed by the time it reaches the lower part of the chamber 510 as long as the coalescence of the droplets D can be suppressed. A configuration may be provided in which the fine particles collected by the collection unit 520, which will be described later, are additionally dried.

<< Droplet forming device >>
The droplet forming device 1 includes a discharge unit 10 and a raw material liquid supply unit 19.

<Discharge section>
As the ejection unit, for example, any one of the following (1) to (3), which is a known configuration as a device for ejecting droplets, can be adopted.
(1) Configuration using "volume changing means" in which the volume of the liquid storage unit is changed by using vibration (2) Liquid is discharged from a plurality of discharge holes provided in the liquid storage unit while applying vibration to the liquid storage unit. Configuration using a "constriction generating means" in which a liquid is atomized from a columnar state into droplets (3) A configuration using a "nozzle vibrating means" that vibrates a thin film in which a nozzle is formed.

<Volume change means>
The volume changing means is not particularly limited as long as the volume of the liquid accommodating portion can be changed, and can be appropriately selected according to the purpose. For example, a piezoelectric element (referred to as a "piezo element") that expands and contracts when a voltage is applied. (May be), an electric heat conversion element such as a heat generation resistor, and the like.

<Means for generating constriction>
As the constriction generating means, for example, there is one using the technique described in Japanese Patent Application Laid-Open No. 2007-199463. In Japanese Patent Application Laid-Open No. 2007-199463, the raw material liquid is discharged from a plurality of nozzle holes provided in the liquid storage unit while vibrating the liquid storage unit by a vibrating means using a piezoelectric element in contact with a part of the liquid storage unit. It is conceivable that the raw material fluid is released and atomized from a columnar state through a constricted state.

<Nozzle vibration means>
As the nozzle vibration means, for example, there is a method using the technique described in Japanese Patent Application Laid-Open No. 2008-292976. In Japanese Patent Application Laid-Open No. 2008-29297, a plurality of thin films having a plurality of nozzles provided in a liquid storage portion, and a plurality of piezoelectric elements arranged around the deformable region of the thin film to vibrate the thin film are used. It is conceivable that the raw material liquid is discharged from the nozzle hole to form droplets.

Hereinafter, as an example, a droplet forming apparatus using a discharge unit having a constriction generating means will be described with reference to FIGS. 1 and 2. FIG. 2 is a partially enlarged view of the discharge portion.

The discharge unit 10 discharges droplets of the raw material liquid described later. The discharge unit 10 has a liquid chamber 10A for storing the raw material liquid and a discharge hole 102x communicating with the liquid chamber 10A. The raw material liquid stored in the liquid chamber 10A is discharged through the discharge hole 102x, and is formed into a spherical shape in the gas phase due to the surface tension of the raw material liquid.

The discharge unit 10 has a discharge head 100 having a liquid chamber 10A and a discharge hole 102x, and a discharge unit main body 110 to which the discharge head 100 is connected. The discharge head 100 may be configured to be detachable from the discharge unit main body 110.

The discharge head 100 is not particularly limited as long as it has the liquid chamber 10A, and the shape, size, and the like can be appropriately selected according to the purpose. The discharge head 100 shown in FIGS. 1 and 2 is provided at the lower end of the discharge portion 10 having a cylindrical shape. The side surface 100a of the discharge head 100 is a cylindrical surface and is curved.

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

The discharge head 100 presses the head body provided with the liquid chamber 10A, the nozzle plate 102 forming a part of the wall surface of the liquid chamber 10A, and the nozzle plate 102 against the head body, and makes contact between the head body and the nozzle plate 102. It has a cover 103 that holds the surface liquidtightly.

The nozzle plate 102 has a plurality of discharge holes 102x. The cross-sectional shape and size of the discharge hole 102x can be appropriately selected.

The cross-sectional shape of the discharge hole 102x is not particularly limited and may be appropriately selected depending on the intended purpose. for example,
(1): Tapered shape so that the opening diameter decreases from the inside (liquid chamber side) to the outside (the side where the liquid is discharged) (2): The outside (the liquid is discharged) from the inside (liquid chamber side) Shape that narrows the opening diameter while having a round shape toward the side) (3): Opening diameter with a constant nozzle angle from the inside (liquid chamber side) to the outside (the side where the liquid is discharged) (4): A combination of the shape of (1) and the shape of (2) is mentioned. The nozzle angle and the taper angle may be constant from the inside to the outside, may change continuously, or may change discontinuously (stepwise).

The nozzle angle in the shape of (3) is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 60 ° or more and 90 ° or less. When the nozzle angle is 60 ° or more, pressure is likely to be applied to the liquid, and further processing is easy. When the nozzle angle is 90 ° or less, pressure is applied in the ejection hole, so that the droplet ejection can be stabilized. Therefore, it is preferable that the maximum nozzle angle is 90 °.

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

The discharge head 100 has a vibrating portion that vibrates the raw material liquid stored in the liquid chamber 10A inside. A piezoelectric element is generally used as the vibrating part. The piezoelectric element is not particularly limited, and the shape, size, and material can be appropriately selected. For example, the piezoelectric element used in the conventional inkjet ejection method can be preferably used.

The shape and size of the piezoelectric element are not particularly limited, and can be appropriately selected according to the shape of the discharge hole and the like.

The material of the piezoelectric element is not particularly limited and may be appropriately selected depending on the intended purpose. For example, piezoelectric ceramics such as lead zirconate titanate (PZT), piezoelectric polymers such as polyvinylidene fluoride (PVDF), and crystals. , LiNbO ₃ , LiTaO ₃ , KNbO ₃ , and the like.

The discharge head 100 can make the raw material liquid into droplets by discharging the raw material liquid from the liquid chamber 10A through the discharge hole 102x while applying vibration to the raw material liquid in the liquid chamber 10A by the vibrating portion.

The raw material liquid supply unit 19 includes a raw material liquid tank 191 for storing the raw material liquid, a pipe 192 for connecting the raw material liquid tank 191 and the discharge head 100, and a pump 193 provided in the path of the pipe 192. The raw material liquid supply unit 19 supplies the raw material liquid L1 stored in the raw material liquid tank 191 to the liquid chamber 10A.

The means for supplying the raw material liquid L1 from the raw material liquid tank 191 to the liquid chamber 10A is a pressurizing means for increasing the internal pressure of the raw material liquid tank 191 for pumping the raw material liquid, in addition to the pump 192 provided in the piping path. You may.

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

--Base material--
The base material is a base material that constitutes the particles. Therefore, it is preferable that it is solid at room temperature. The base material is not particularly limited as long as it is not a substance that adversely affects the physiologically active substance contained therein, and may be a substance having a low molecular weight or a substance having a high molecular weight, but the particles of the present invention may be used. Is preferably a particle that is applied to a living body, so that the substrate is preferably a substance that is not toxic to the living body. The low molecular weight substance is preferably a compound having a weight average molecular weight of less than 15,000. The high molecular weight substance is preferably a compound having a weight average molecular weight of 15,000 or more. As described above, the base material may be only one type or two or more types, and any base material described later may be used in combination.

-Low molecular weight substances-
The low molecular weight substance is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include lipids, saccharides, cyclodextrins, amino acids, and organic acids. These may be used alone or in combination of two or more.

－－Lipids －－
The lipids are not particularly limited and may be appropriately selected depending on the intended purpose. For example, medium-chain or long-chain monoglycerides, medium-chain or long-chain diglycerides, medium-chain or long-chain triglycerides, phospholipids, etc. Vegetable oils (eg soybean oil, avocado oil, squalane oil, sesame oil, olive oil, corn oil, rapeseed oil, safflower oil, sunflower oil, etc.), fish oils, seasoning oils, water-insoluble vitamins, fatty acids, mixtures thereof, and their mixtures. Examples include derivatives. These may be used alone or in combination of two or more.

－－Sugars－－
The saccharide is not particularly limited and may be appropriately selected depending on the intended purpose. For example, glucose, mannose, idose, galactose, fucose, ribose, xylose, lactose, sucrose, maltose, trehalose, turanose, raffinose and maltotri. In addition to monosaccharides and polysaccharides such as aus, acarbose, cyclodextrins, amylose (starch) and cellulose, sugar alcohols (polyol) such as glycerin, sorbitol, lactitol, maltose, mannitol, xylitol and erythritol, and derivatives thereof. And so on. These may be used alone or in combination of two or more.

--Cyclodextrins ---
The cyclodextrins are not particularly limited and may be appropriately selected depending on the intended purpose. For example, hydroxypropyl-β-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, α-cyclodextrin, and cyclodextrin. Examples include derivatives. These may be used alone or in combination of two or more.

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

－－Organic acids －－
The organic acids are not particularly limited and may be appropriately selected depending on the intended purpose. For example, adipic acid, ascorbic acid, citric acid, fumaric acid, gallic acid, glutaric acid, lactic acid, malic acid, mylenic acid and succinic acid. Acids, glutaric acid, and derivatives thereof and the like can be mentioned. These may be used alone or in combination of two or more.

-High molecular weight substance-
The high molecular weight substance is not particularly limited and may be appropriately selected depending on the intended purpose. For example, water-soluble cellulose, polyalkylene glycol, poly (meth) acrylamide, poly (meth) acrylic acid, poly (meth). Examples thereof include proteins such as acrylic acid esters, polyallylamines, polyvinylpyrrolidones, polyvinyl alcohols, polyvinylacetates, biodegradable polyesters, polyglycolic acids, polyamino acids, gelatins and fibrins, polysaccharides and derivatives thereof. These may be used alone or in combination of two or more.

－－Water-soluble cellulose －－
The water-soluble cellulose is not particularly limited and may be appropriately selected depending on the intended purpose. For example, alkyl cellulose such as methyl cellulose and ethyl cellulose; hydroxyalkyl cellulose such as hydroxyethyl cellulose and hydroxypropyl cellulose; and hydroxyethyl methyl cellulose and hydroxy. Examples thereof include hydroxyalkylalkyl cellulose such as propylmethyl cellulose. These may be used alone or in combination of two or more. Among these, hydroxypropyl cellulose and hydroxypropyl methyl cellulose are preferable, and hydroxypropyl cellulose is more preferable, because they have high biocompatibility and high solubility in a solvent used for producing particles.

--- Hydroxypropyl Cellulose ---
Various products having different viscosities of hydroxypropyl cellulose are commercially available from various companies, and all of them can be used as the base material of the present invention. The viscosity of the 2% by mass aqueous solution (20 ° C.) of hydroxypropyl cellulose is not particularly limited and may be appropriately selected depending on the intended purpose, but is 2.0 mPa · s (centipoise, cps) or more and 4,000 mPa · s ( Centipoise, cps) or less is preferable.

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

The commercially available hydroxypropyl cellulose is not particularly limited and may be appropriately selected depending on the intended purpose. For example, the molecular weight is 15,000 or more and 30,000 or less, and the viscosity is 2.0 mPa · s or more and 2.9 mPa · s. HPC-SL, etc. with 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, such as HPC-SL, a molecular weight of 55,000 or more and 70,000 or less, and a viscosity of 6 HPC-L, etc. with a molecular weight of 1.0 mPa · s or more and 10.0 mPa · s or less, HPC-M, etc. with 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, and a molecular weight of 250,000 or more and 400 Examples thereof include HPC-H and the like (all manufactured by Nippon Soda Co., Ltd.) having a viscosity of 1,000 mPa · s or more and 4,000 mPa · s or less. These may be used alone or in combination of two or more. Among these, HPC-SSL having 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 preferable. In the above-mentioned commercial product, the molecular weight is measured by gel permeation chromatography (GPC), and the viscosity is measured by using a 2% by mass aqueous solution (20 ° C.).

The content of hydroxypropyl cellulose is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 50% by mass or more, more preferably 50% by mass or more and 99% by mass or less, based on the mass of the base material. It is more preferably 75% by mass or more and 99% by mass or less, and particularly preferably 80% by mass or more and 99% by mass or less.

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

－－Poly (meth) acrylamide －－
The poly (meth) acrylamide is not particularly limited and may be appropriately selected depending on the intended purpose. For example, N-methyl (meth) acrylamide, N-ethyl (meth) acrylamide, N-propyl (meth) acrylamide, etc. N-butyl (meth) acrylamide, N-benzyl (meth) acrylamide, N-hydroxyethyl (meth) acrylamide, N-phenyl (meth) acrylamide, N-trill (meth) acrylamide, N- (hydroxyphenyl) (meth) Acrylamide, N- (sulfamoylphenyl) (meth) acrylamide, N- (phenylsulfonyl) (meth) acrylamide, N- (trillsulfonyl) (meth) acrylamide, N, N-dimethyl (meth) acrylamide, N-methyl Examples thereof include polymers of monomers such as -N-phenyl (meth) acrylamide and N-hydroxyethyl-N-methyl (meth) acrylamide. These monomers may be polymerized individually by 1 type, or may be polymerized in combination of 2 or more types. Further, these polymers may be used alone or in combination of two or more.

－－Poly (meth) acrylic acid －－
The poly (meth) acrylic acid is not particularly limited and may be appropriately selected depending on the intended purpose. For example, homopolymers such as polyacrylic acid and polymethacrylic acid, and copolymers of acrylic acid-methacrylic acid copolymer and the like. And so on. These may be used alone or in combination of two or more.

－－Poly (meth) acrylic acid ester －－
The poly (meth) acrylic acid ester is not particularly limited and may be appropriately selected depending on the intended purpose. For example, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, propylene glycol di (meth) acrylate. , Polymers of monomers such as glycerol poly (meth) acrylate, polyethylene glycol (meth) acrylate, trimethylolpropane tri (meth) acrylate, pentaerythritol tetra (meth) acrylate, 1,3-butylene glycol di (meth) acrylate Can be mentioned. These monomers may be polymerized individually by 1 type, or may be polymerized in combination of 2 or more types. Further, these polymers may be used alone or in combination of two or more.

－－Polyallylamine －－
The polyallylamine is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include diallylamine and triallylamine. These may be used alone or in combination of two or more.

－－Polyvinylpyrrolidone －－
As the polyvinylpyrrolidone, a commercially available product can be used. The commercially available polyvinylpyrrolidone is not particularly limited and may be appropriately selected depending on the intended purpose. For example, Plasdon C-15 (manufactured by ISP TECHNOLOGIES), Corridon VA64, Corridon K-30, Corridon CL-M ( As mentioned above, KAWARLAL), Coricort IR (BASF) and the like can be mentioned. These may be used alone or in combination of two or more.

－－Polyvinyl alcohol －－
The polyvinyl alcohol is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include silanol-modified polyvinyl alcohol, carboxyl-modified polyvinyl alcohol, and acetoacetyl-modified polyvinyl alcohol. These may be used alone or in combination of two or more.

--Polyvinyl acetate ---
The polyvinyl acetate is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include vinyl acetate-crotonic acid copolymer and vinyl acetate-itaconic acid copolymer. These may be used alone or in combination of two or more.

--Biodegradable polyester ---
The biodegradable polyester is not particularly limited and may be appropriately selected depending on the intended purpose. For example, polylactic acid; poly-ε-caprolactone; polyethylene succinate, polybutylene succinate, polybutylene succinate adipate and the like can be selected. Succinate-based polymers; examples thereof include polyhydroxypropionate, polyhydroxybutyrate, polyhydroxyalkanoate such as polyhydroxyparilate, and polyglycolic acid. These may be used alone or in combination of two or more. Among these, polylactic acid is preferable because it has high biocompatibility and can elute the contained physiologically active substance in a sustained-release manner.

－－－ Polylactic acid －－－
The weight average molecular weight of polylactic acid is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 5,000 or more and 100,000 or less, more preferably 10,000 or more and 70,000 or less. It is more preferably 000 or more and 50,000 or less, and particularly preferably 10,000 or more and 30,000 or less.

The content of polylactic acid is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 50% by mass or more, more preferably 50% by mass or more and 99% by mass or less, and 75 by mass with respect to the mass of the base material. It is more preferably mass% or more and 99% by mass or less, and particularly preferably 80% by mass or more and 99% by mass or less.

--- Polyglycolic acid ---
The polyglycolic acid is not particularly limited and may be appropriately selected depending on the intended purpose. For example, lactic acid / glycolic acid, which is a copolymer having a structural unit derived from lactic acid and a structural unit derived from glycolic acid. Glycolic acid-caprolactone copolymer, which is a copolymer having a copolymer, a constituent unit derived from glycolic acid and a constituent unit derived from caprolactone, a constituent unit derived from glycolic acid and a constituent unit derived from trimethylene carbonate. Glycolic acid / trimethylene carbonate copolymer, which is a copolymer having the above, and the like can be mentioned. These may be used alone or in combination of two or more. Among these, a lactic acid / glycolic acid copolymer has high biocompatibility, can elute the contained bioactive substance in a sustained-release manner, and can store the contained physiologically active substance for a long period of time. Is preferable.

The weight average molecular weight of the lactic acid / glycolic acid copolymer is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 2,000 to 250,000, more preferably 2,000 to 100,000. It is preferable, 3,000 to 50,000 is more preferable, and 5,000 to 10,000 is particularly preferable.

The molar ratio (L: G) of the lactic acid-derived structural unit (L) and the glycolic acid-derived structural unit (G) in the lactic acid / glycolic acid copolymer is not particularly limited and may vary depending on the intended purpose. Although it can be appropriately selected, it is preferably 1:99 to 99: 1, more preferably 25:75 to 99: 1, still more preferably 30:70 to 90:10, and particularly preferably 50:50 to 85:15. ..

The content of the lactic acid / glycolic acid copolymer is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 50% by mass or more and 99% by mass or less with respect to the mass of the base material. Is more preferable, 75% by mass or more and 99% by mass or less is further preferable, and 80% by mass or more and 99% by mass or less is particularly preferable.

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

--gelatin--
The gelatin is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include lime-treated gelatin, acid-treated gelatin, gelatin hydrolysate, gelatin enzyme dispersion, and derivatives thereof. These may be used alone or in combination of two or more.

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

The gelatin derivative means gelatin derivatized by covalently bonding a hydrophobic group to a gelatin molecule. The hydrophobic group is not particularly limited and may be appropriately selected depending on the intended purpose. For example, polyesters such as polylactic acid, polyglycolic acid and poly-ε-caprolactone; lipids such as cholesterol and phosphatidylethanolamine; Examples include an alkyl group, an aromatic group containing a benzene ring; a heteroaromatic group, or a mixture thereof.

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

The polysaccharide is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include chitin, chitosan, hyaluronic acid, alginic acid, starch and pectin. These may be used alone or in combination of two or more.

Since the base material is preferably a substance that can contain particles containing the base material in pharmaceutical preparations, functional foods, functional cosmetics, etc., among the above materials, substances having no biotoxicity, particularly It is preferably a biodegradable substance such as a biodegradable polymer.

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

Examples of the solvent include aliphatic halogenated hydrocarbons (eg, dichloromethane, dichloroethane, chloroform, etc.), alcohols (eg, methanol, ethanol, propanol, etc.), ketones (eg, acetone, methyl ethyl ketone, etc.), ethers, etc. (Eg, diethyl ether, dibutyl ether, 1,4-dioxane, etc.), aliphatic hydrocarbons (eg, n-hexane, cyclohexane, n-heptane, etc.), aromatic hydrocarbons (eg, benzene, toluene, xylene, etc.) Etc.), organic acids (eg, acetic acid, propionic acid, etc.), esters (eg, ethyl acetate, etc.), amides (eg, dimethylformamide, dimethylacetamide, etc.) and the like. These may be used alone or in combination of two or more. Among these, aliphatic halogenated hydrocarbons, alcohols, ketones or a mixed solvent thereof is preferable from the viewpoint of solubility, and dichloromethane, 1,4-dioxane, methanol, ethanol, acetone, or a mixed solvent thereof is preferable. More preferred.

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

－－Other ingredients －－
The other components are not particularly limited and may be appropriately selected depending on the intended purpose.
Other ingredients include, for example, water, excipients, flavoring agents, disintegrants, fluidizers, adsorbents, lubricants, deodorants, surfactants, fragrances, colorants, antioxidants, concealing agents, etc. Examples include antistatic agents and wetting agents. These may be used alone or in combination of two or more.

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

The flavoring agent is not particularly limited and may be appropriately selected depending on the intended purpose. For example, L-menthol, sucrose, D-sorbitol, xylitol, citric acid, ascorbic acid, tartaric acid, malic acid, aspartame, and acesulfame potassium. , Somatin, sodium saccharin, dipotassium glycyrrhizinate, sodium glutamate, 5'-sodium inosinate, 5'-sodium guanylate and the like. These may be used alone or in combination of two or more.

The disintegrant is not particularly limited and may be appropriately selected depending on the intended purpose. For example, low-substituted hydroxypropyl cellulose, carmellose, carmellose calcium, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, hydroxy. Examples include propyl starch and corn starch. These may be used alone or in combination of two or more.

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

As the light anhydrous silicic acid, a commercially available product can be used. The commercially available product of light anhydrous silicic acid is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include Addolider 101 (manufactured by Freund Sangyo Co., Ltd .: average pore diameter: 21 nm).

As the adsorbent, a commercially available product can be used. The commercially available adsorbent is not particularly limited and may be appropriately selected depending on the purpose. For example, product name: Carplex (component name: synthetic silica, registered trademark of DSL. Japan Co., Ltd.), product name. : Aerosil (registered trademark of Nippon Aerosil Co., Ltd.) 200 (ingredient name: hydrophilic fumed silica), trade name: Cyricia (ingredient name: amorphous silicon dioxide, registered trademark of Fuji Silicia Chemical Co., Ltd.), trade name: Alcamac (ingredient name: synthetic hydrotalcite, registered trademark of Kyowa Kagaku Co., Ltd.) and the like can be mentioned. These may be used alone or in combination of two or more.

The lubricant is not particularly limited and may be appropriately selected depending on the intended purpose. For example, magnesium stearate, calcium stearate, sucrose fatty acid ester, sodium stearyl fumarate, stearic acid, polyethylene glycol, talc and the like can be used. Can be mentioned. These may be used alone or in combination of two or more.

The odorant is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include trehalose, maltose, maltose, potassium gluconate, anise essential oil, vanilla essential oil and cardamom essential oil. These may be used alone or in combination of two or more.

The surfactant is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include polysorbate such as polysorbate 80; polyoxyethylene / polyoxypropylene copolymer; and sodium lauryl sulfate. These may be used alone or in combination of two or more.

The fragrance is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include lemon oil, orange oil and peppermint oil. These may be used alone or in combination of two or more.

The colorant is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include titanium oxide, edible yellow No. 5, edible blue No. 2, iron sesquioxide, and yellow sesquioxide. These may be used alone or in combination of two or more.

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

The concealing agent is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include titanium oxide. These may be used alone or in combination of two or more.

The antistatic agent is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include talc and titanium oxide. These may be used alone or in combination of two or more.

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

As the raw material liquid, a solution in which a physiologically active substance is dissolved in a solvent and a dispersion liquid in which the physiologically active substance is dispersed in a dispersion medium can be used. Further, the raw material liquid may not contain a solvent as long as it is liquid under the conditions of discharge, and may be in a state where the solid content contained in the raw material liquid is melted.

As shown in FIG. 2, the plurality of discharge holes 102x are arranged horizontally on the side surface 100a of the discharge portion 10 (discharge head 100) to form a nozzle row C. The wording horizontal direction refers to a direction parallel to the xy plane in the xyz Cartesian coordinate system, but the arrangement direction of the discharge holes 102x does not have to be strictly parallel to the xy plane in the configuration of the discharge unit 10. For example, it may be inclined by about ± 10 ° with respect to the xy plane.

As described above, the side surface 100a of the discharge head 100 is a cylindrical surface, and the plurality of discharge holes 102x are arranged in the circumferential direction of the cylindrical surface. Since the droplet D is ejected from the ejection hole 102x in the radial direction of the ejection head 100, it can be said that the side surface 100a is convex in the ejection direction of the droplet D.

In the discharge head 100 having such a configuration, the droplets D (droplets D1 and D2) discharged from the adjacent discharge holes 102x are separated from each other as the distance from the discharge head 100 increases. Therefore, it is preferable that the droplet D ejected from the ejection head 100 has a problem that the particle size is changed due to coalescence in the air, and the particle size of the droplet D can be easily maintained as set.

FIG. 3 is an enlarged view illustrating the arrangement of the discharge holes 102x. FIG. 3 shows a state in which the curved nozzle plate 102 is stretched.

As shown in FIG. 3, the nozzle plate 102 has a plurality of (two in the figure) first nozzle row C1 and a second nozzle row C2. Hereinafter, the first nozzle row C1 is abbreviated as "nozzle row C1", and the second nozzle row C2 is abbreviated as "nozzle row C2".

The nozzle row C1 and the nozzle row C2 are arranged in a direction α that intersects the extending direction (horizontal direction) of each nozzle row.

Further, in the nozzle plate 102, the plurality of discharge holes 102x included in the nozzle row C1 and the plurality of discharge holes 102x included in the nozzle row C2 are spaced apart at equal intervals. The intervals between the plurality of discharge holes 102x do not have to be equal.

Further, the plurality of discharge holes 102x included in the nozzle row C1 and the plurality of discharge holes 102x included in the nozzle row C2 are arranged in a staggered manner. In FIG. 3, in the staggered arrangement, the discharge holes 102x of the nozzle row C1 and the discharge holes 102x of the nozzle row C2 are alternately provided from one end side to the other end side in the extending direction of the nozzle rows C1 and C2. Refers to placement. Therefore, the discharge holes A of the nozzle row C1 and the discharge holes X1 and X2 of the nozzle row C2 do not overlap in the z-axis direction.

The arrangement of the discharge holes 102x as described above is designed based on the following ideas.

First, when the raw material liquid is discharged from the discharge hole 102x to form droplets, the raw material liquid adheres to the side surface 100a around the discharge hole 102x, and a part of the solid content contained in the raw material liquid L1 is deposited, so that the raw material liquid is almost formed. Dirt inevitably adheres. When such dirt accumulates, it becomes impossible to discharge from the discharge hole 102x as set, and various discharge defects occur.

Examples of the assumed ejection failure include the following states (1) to (4).
(1) The discharge hole 102x is completely closed and the droplet cannot be discharged.
(2) A part of the discharge hole 102x is closed and the particle size of the droplet becomes smaller than the setting.
(3) Although droplets cannot be discharged from the discharge hole 102x, the raw material liquid is discharged and spreads around the discharge hole 102x.
(4) Dirt is accumulated on a part of the edge of the discharge hole 102x, so that the dirt is tilted with respect to the central axis of the discharge hole 102x.

Further, when the dirt is accumulated, it is expected that the dirt discharge hole 102x and the adjacent discharge hole 102x are also affected. The dirt on the discharge hole 102x can be removed by, for example, disassembling and cleaning the discharge head 100, but it is necessary to stop the production for cleaning, which leads to a decrease in productivity.

The inventors considered that the deterioration of productivity could be suppressed from the design of the discharge head 100 against the dirt around the discharge hole 102x generated as described above, and as a result of various studies, the present invention was completed.

First, in the droplet forming apparatus 1 of the present embodiment, the ejection holes 102x are provided on the side surface of the ejection head 100. In the present art, there is also a conventional technique in which a discharge hole is provided on the lower surface of a discharge head. However, in such a configuration, when the droplet is ejected, the raw material liquid is isotropically adhered around the ejection hole 102x around the ejection hole, and as a result, the dirt generated in the ejection hole is centered on the ejection hole and the like. It is thought that it spreads anisotropically to the surroundings. Therefore, dirt generated in the discharge holes may affect a plurality of surrounding discharge holes.

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

Next, the behavior of the raw material liquid dripping from the discharge hole 102x will be considered. FIG. 4 is a schematic view showing a state around the discharge hole 102x on the side surface 100a.

The raw material liquid that hangs down from the discharge hole 102x in the −z direction gradually volatilizes the solvent while spreading in the horizontal direction, solidifies and stops. FIG. 4 schematically shows the spread of such a raw material liquid. It can be assumed that the raw material liquid dripping from the discharge hole 102x spreads over a range AR of a distance L from the center of the discharge hole 102x and a width W at the lower end.

If the adjacent discharge hole 102x (indicated by reference numeral Y1) exists in the dripping range AR thus assumed, the discharge hole Y1 is expected to be affected by the dripping and cause a discharge failure.

On the other hand, even if the position is the same as the discharge hole Y1, the discharge hole 102x (indicated by the reference numeral Y2) existing outside the range AR is not expected to be affected by the dripping.

In the ejection head 100 included in the droplet forming apparatus 1, the positions of a plurality of ejection holes 102x are set based on the above idea.

The range AR is the volatility (vapor pressure) of the solvent contained in the raw material liquid, the concentration of the raw material liquid, the contact angle between the nozzle plate 102 and the raw material liquid, the temperature in the chamber of the fine particle manufacturing apparatus, and the partial pressure of the solvent in the chamber. It is considered to be affected by various conditions such as. Of these, the temperature and partial pressure in the chamber, which are the operating conditions, can be controlled. Therefore, when the raw material liquid is discharged using a specific nozzle plate 102, the raw material liquid is prepared by a preliminary experiment, and the adjacent discharge hole 102x is located in the range AR with respect to the arrangement of the discharge holes 102x of the nozzle plate 102. It is advisable to set the prescription of the raw material liquid that is not included.

The nozzle plate 102 may be designed so that the adjacent discharge hole 102x is not provided in the locus when the discharge hole 102x is translated in the −z direction with respect to the discharge hole 102x.

Further, in the nozzle plate 102 shown in the figure, two rows of nozzle rows C are set, but the present invention is not limited to this, and three or more rows of nozzle rows may be arranged.

On the contrary, in the nozzle plate 102, the nozzle row C may be only one row. In this case, from the viewpoint of the influence of the processing accuracy and the material strength of the nozzle plate and the prevention of coalescence of formed droplets, there is a theoretical upper limit to the distance between the discharge holes 102x adjacent to each other in the horizontal direction. Therefore, for the purpose of increasing the amount of droplets ejected from the ejection head 100, it is better to have a plurality of nozzle rows C.

According to the droplet forming apparatus 1 having the above configuration, the droplet forming apparatus can be made less susceptible to the influence of dirt adhering to the periphery of the nozzle.

Further, according to the fine particle manufacturing apparatus 500 having the above configuration, the droplet forming apparatus is provided, and stable production of high quality fine particles is possible.

Although the preferred embodiments of the present invention have been described above with reference to the accompanying drawings, the present invention is not limited to these examples. The various shapes and combinations of the constituent members shown in the above-mentioned example are examples, and can be variously changed based on design requirements and the like within a range not deviating from the gist of the present invention.

The present invention includes the following aspects.

[1] The discharge head has a discharge head for discharging droplets of a raw material liquid, the discharge head has a plurality of discharge holes, the plurality of discharge holes are formed on the side surface of the discharge head, and the plurality of discharge holes are formed. Is a droplet forming device provided at a position on the side surface thereof that does not overlap with a virtual range where the raw material liquid is assumed to dripping from the discharge hole.

[2] The droplet forming apparatus according to [1], wherein the plurality of ejection holes form a horizontally arranged nozzle array.

[3] The droplet forming apparatus according to [2], which has a plurality of the nozzle rows, and the plurality of nozzle rows are arranged in a direction intersecting the extending direction of the nozzle rows on the side surface.

[4] The plurality of discharge holes included in the first nozzle row and the plurality of discharge holes included in the second nozzle row adjacent to the first nozzle row are arranged in a staggered manner [3]. Droplet forming device.

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

[6] The droplet forming apparatus according to any one of [1] to [5], wherein the side surface is convex in the ejection direction of the droplet.

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

[8] A fine particle manufacturing apparatus comprising the droplet forming apparatus according to any one of [1] to [7] and a solidifying means for solidifying the droplets ejected from the droplet forming apparatus.

1 ... Droplet forming device, 100 ... Discharge head, 100a ... Side surface, 102x, A, X1, X2, Y1, Y2 ... Discharge hole, 500 ... Fine particle production device, AR ... Range, C ... Nozzle row, C1 ... 1st Nozzle row, C2 ... Second nozzle row, D, D1, D2 ... Droplets, L1 ... Raw material liquid

Japanese Unexamined Patent Publication No. 2019-177371

Claims (8)

It has a discharge head that discharges droplets of raw material liquid, and has a discharge head.
The discharge head has a plurality of discharge holes and has a plurality of discharge holes.
The plurality of discharge holes are formed on the side surface of the discharge head.
Each of the plurality of discharge holes is provided at a position on the side surface thereof so as not to overlap with a virtual range where the raw material liquid is assumed to drip from the discharge holes. The droplet forming apparatus according to claim 1, wherein the plurality of ejection holes form a horizontally arranged nozzle array. Having a plurality of the nozzle rows,
The droplet forming apparatus according to claim 2, wherein the plurality of nozzle rows are arranged in a direction intersecting the extending direction of the nozzle rows on the side surface. The droplet formation according to claim 3, wherein the plurality of ejection holes included in the first nozzle array and the plurality of ejection holes included in the second nozzle array adjacent to the first nozzle array are staggered. Device. The droplet forming apparatus according to claim 3 or 4, wherein the plurality of ejection holes included in the nozzle row are spaced apart from each other at equal intervals. The droplet forming apparatus according to any one of claims 1 to 5, wherein the side surface is convex in the ejection direction of the droplet. The droplet forming apparatus according to claim 6, wherein the side surface is a cylindrical surface. The droplet forming apparatus according to any one of claims 1 to 7.
A fine particle manufacturing apparatus comprising a solidifying means for solidifying droplets ejected from the droplet forming apparatus.

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