Patent Application
20250091060
The present disclosure relates to a disperser capable of producing nanoparticles by low-power dispersing. Specifically, the present disclosure relates to a high-performance disperser capable of nano-level dissolution and macromolecular dissolution as well as nanoparticle production, which can also be used for crystallization and emulsion polymerization, and a method for using the same.
In the pharmaceutical and chemical industries, nanoparticles have entered the stage of practical use. For example, vaccines against novel coronavirus infection (COVID-19) are known worldwide. RNA vaccines are the first COVID-19 vaccines to be authorized in the United States and the European Union. The RNA vaccine contains ribonucleic acid (RNA), and when introduced into human tissue, messenger RNA (mRNA) induces cells to produce foreign proteins and stimulates an adaptive immune response, teaching the body how to identify and destroy the corresponding pathogen. Although not always the case, RNA vaccines often use nucleotide-modified mRNA. The delivery of mRNA is achieved by a co-formulation of the molecule into lipid nanoparticles, which protect the RNA strands and help their absorption into the cells. The particle size is said to be 100 nm. In addition, other types of vaccines such as virus-like particle vaccines and DNA plasmid vaccines are in clinical trials, and many nanospheres, liposomes, nanoemulsions, and the like are being developed. Therefore, there is a need for a disperser that produces ultrafine particles with controlled shear force, especially one that can produce fine particles for injection.
Patent Document 1 discloses a high-performance stirring disperser. In the disperser, blades rotate at high speed in a tank, and a screen with slits rotates at high speed in the opposite direction to the blades, creating a jet stream that provides a shear force to atomize a fluid into fine particles. The problem with the disperser is that it requires a lot of power.
Patent Document 2 discloses a manufacturing method for producing lipid emulsions and liposomes in a short time and with low power. In this manufacturing method, a phospholipid-containing material to be treated is pressurized and subjected to high-speed rotation to atomize it into fine particles. At this time, air spaces are eliminated because if they are present in the dispersion tank, many small air bubbles are mixed into the material to be treated, creating a pseudo-compressible fluid and making it difficult to properly apply a shear force. The manufacturing method also requires a considerable amount of power.
Patent Document 3 discloses a flow reactor (continuous reactor) that has a high heat exchange rate and can be disassembled. Although excellent as a flow reactor, it has too little shear force to be used as a disperser, and it is difficult for the reactor to produce nanoparticles for the above-mentioned vaccines or the like.
Patent Document 4 discloses a gap shear disperser that includes a conical rotor and a conical vessel with a sloped inner wall that concentrically houses the rotor. The shear disperser is designed for uniform atomization of viscous materials such as pastes. Considering the structure and the center runout caused by the rotation of the rotor, it is difficult to make the gap between the rotor and the vessel in microns. Even if the gap between the rotor and the vessel is made in microns, due to the hollowing phenomenon that occurs in the gap when a viscous fluid is treated, it is difficult to apply a shear force to the material being treated.
In view of the foregoing, it is an object of the present disclosure to provide a disperser capable of producing fine particles, especially nanoparticles, by efficiently applying a shear force to a material to be treated with low power, and a method for using the same.
To achieve the object mentioned above, according to the first aspect of the invention, a disperser includes: a cylindrical outer member extending in a predetermined direction and having a tapered inner circumferential surface as a part of the inner circumferential surface thereof; an inner member located radially inside the outer member and having a tapered outer circumferential surface as a part of the outer circumferential surface thereof, the tapered outer circumferential surface facing the tapered inner circumferential surface of the outer member; and a clearance adjustment part that allows a distance clearance between the tapered inner circumferential surface and the tapered outer circumferential surface to be adjusted by moving the outer member and the inner member relative to each other in the predetermined direction. A flow path is formed between the inner circumferential surface of the outer member and the outer circumferential surface of the inner member, through which fluid flows from one side to the other side in the predetermined direction. The flow path includes a dispersion region defined by the tapered inner circumferential surface and the tapered outer circumferential surface. The tapered inner circumferential surface and the tapered outer circumferential surface are formed such that the angle of one with respect to the other (the angle therebetween) in a cross section in the predetermined direction changes in the middle of the dispersion region.
According to the second aspect of the invention, in the disperser of the first aspect, the dispersion region of the flow path includes: a reduction region where the clearance distance decreases from the one side to the other side, and a constant region extending continuously from the reduction region to the other side, where the clearance distance is constant.
According to the third aspect of the invention, in the disperser of the first or second aspect, the clearance adjustment part includes: a fixing member that supports the inner member to be slidable in the predetermined direction and is fixed to the outer member, and a differential screw configured to slide the inner member in the predetermined direction with respect to the fixing member.
According to the fourth aspect of the invention, in the disperser of the first or second aspect, the clearance adjustment part can be used to selectively place the disperser in any one of the following states without disassembling the outer member and the inner member: a contact state in which the tapered inner circumferential surface and the tapered outer circumferential surface are in contact with each other, a use state in which the disperser is used and the clearance distance is small, and a separate state in which the clearance distance is larger than in the use state.
According to the fifth aspect of the invention, in the disperser of the second aspect, the constant region of the dispersion region of the flow path has a length of 1 mm or more from the one side to the other side along the flow path direction in the cross section in the predetermined direction.
According to the sixth aspect of the invention, in the disperser of the second aspect, in the constant region of the dispersion region of the flow path, the clearance distance is 0.1 μm or more and 2 mm or less.
According to the seventh aspect of the invention, in the disperser of the second aspect, regions of the tapered inner circumferential surface and the tapered outer circumferential surface that define the constant region of the dispersion region of the flow path are made of ceramic.
According to the eighth aspect of the invention, in the disperser of the first or second aspect, the inner circumferential surface of the outer member and the outer circumferential surface of the inner member that define the flow path have no horizontal portion where the fluid flowing through the flow path may accumulate.
According to the ninth aspect of the invention, in the disperser of the first or second aspect, the inner circumferential surface of the outer member and the outer circumferential surface of the inner member that define the flow path are covered with a coating made of a corrosion-resistant material.
According to the tenth aspect of the invention, in the disperser of the ninth aspect, the coating is a fluoropolymer coating.
According to the eleventh aspect of the invention, in the disperser of the first or second aspect, at least one of the outer member and the inner member has a jacket through which another fluid can flow to adjust the temperature of the fluid flowing through the flow path.
According to the twelfth aspect of the invention, a method for using the disperser of the fourth aspect includes adjusting the clearance distance to place the disperser in the use state. The adjusting includes: bringing the outer member and the inner member into contact with each other by using the clearance adjustment part to bring the disperser into the contact state; and thereafter separating the tapered inner circumferential surface from the tapered outer circumferential surface to bring the disperser into the use state.
According to the thirteenth aspect of the invention, a method for using the disperser of the fourth aspect includes separating the outer member and the inner member from each other by using the clearance adjustment part to bring the disperser into the separate state for cleaning or sterilization of the flow path.
According to the present disclosure, shear force can be efficiently applied to a material to be treated with low power to produce fine particles, especially nanoparticles.
Hereinafter, exemplary embodiments of the present invention will be described with reference to the accompanying drawings. In the drawings, the arrow “UP” indicates upward, and the line “CL” indicates the central axis of an outer member and an inner member. In the following description, the axial direction refers to a direction along the central axis CL of the outer member and the inner member, while the radial direction refers to a direction perpendicular to the central axis CL. In addition, the white arrow in the drawings indicates the direction of the flow of fluid to be treated. In the following description, the axial direction (predetermined direction) corresponds to the vertical direction (up-down direction), and one side in the axial direction is referred to as the lower side, while the other side in the axial direction is referred to as the upper side.
The disperser of this disclosure is a device that can produce nanoparticles from a fluid as a material to be treated (hereinafter referred to as “fluid to be treated” or simply “fluid”) by finely dispersing the fluid. Note that “disperser” is a general term for equipment used to apply a shear force to a fluid to be treated to obtain a treated product. The disperser may be used not only for the production of fine particles such as nanoparticles, but also for the production of emulsions, liposomes, nanospheres, and the like, as well as for polymer dissolution, complete mixing at the molecular level, crystallization, and emulsion polymerization. In addition, the term “fluid” refers not only to gases and liquids, but also to powders, granules, slurries, and other fluid materials.
As illustrated in
The outer member 11 and the inner member 13 are concentrically arranged so that their central axes CL coincide. There is a gap (space) between an inner circumferential surface 15 of the outer member 11 and an outer circumferential surface 16 of the inner member 13, and the gap serves as a flow path 40 through which a fluid to be treated flows. The flow path 40 allows the fluid to be treated to flow from the lower side (one side in the predetermined direction) to the upper side (the other side in the predetermined direction). Unless otherwise specified, the following describes the structure of the disperser 10 in a state where the outer member 11, the fixing member 12, the inner member 13, and the differential screw 14 are assembled and ready for use (hereinafter referred to as “use state”).
The outer member 11 is formed in a cylindrical shape whose central axis CL extends in a predetermined direction (the vertical direction in this embodiment). The outer member 11 has an upper end opening 11a at the upper end, a lower end opening 11b at the lower end, and the inner circumferential surface 15 extending between the upper end opening 11a and the lower end opening 11b. The upper end opening 11a and the lower end opening 11b are arranged to be concentric with the central axis CL. In this embodiment, the upper end opening 11a is formed to have a larger diameter than the lower end opening 11b. The upper end opening 11a of the outer member 11 serves as an insertion port for inserting the inner member 13 into the outer member 11.
The inner circumferential surface 15 of the outer member 11 defines a space (hereinafter referred to as “internal space”) therein. In this embodiment, the inner circumferential surface 15 of the outer member 11 includes four regions, one on top of another, each having a surface with a different function. In other words, the inner circumferential surface 15 of the outer member 11 includes four surfaces with different functions: an inflow inner circumferential surface 15a, a tapered inner circumferential surface 15b, an outflow inner circumferential surface 15c, and a sealing inner circumferential surface 15d, in this order from bottom to top. That is, the outer member 11 has the tapered inner circumferential surface 15b as a part of the inner circumferential surface 15. The inflow inner circumferential surface 15a, the tapered inner circumferential surface 15b, and the outflow inner circumferential surface 15c of the outer member 11 define the radially outer side of the flow path 40.
The inflow inner circumferential surface 15a of the outer member 11 is located below the tapered inner circumferential surface 15b and extends continuously from the lower end opening 11b of the outer member 11 to the lower end of the tapered inner circumferential surface 15b. In this embodiment, the inflow inner circumferential surface 15a is formed in a cylindrical shape. The inflow inner circumferential surface 15a defines the radially outer side of a space (an inflow region 40a, described later) into which the fluid to be treated first flows. The lower end opening 11b of the outer member 11 is connected to a supply source (not illustrated) for pumping the fluid to be treated and allows the fluid to flow into the flow path 40. In this embodiment, the supply source (not illustrated) pumps the fluid to be treated from the lower end opening 11b of the outer member 11 into the flow path 40 at a pressure of 0.5 MPaG.
The tapered inner circumferential surface 15b of the outer member 11 is a tapered (conical) surface and extends upward continuously from the inflow inner circumferential surface 15a. In this embodiment, the tapered inner circumferential surface 15b is tapered from the top to the bottom. The tapered inner circumferential surface 15b defines the radially outer side of a space (a dispersion region 40b, described later) in which the fluid to be treated can be dispersed. The vertex (not illustrated) of the tapered profile of the tapered inner circumferential surface 15b is located on the central axis CL.
As illustrated in
The outflow inner circumferential surface 15c of the outer member 11 extends upward continuously from the upper end of the tapered inner circumferential surface 15b. In this embodiment, the outflow inner circumferential surface 15c is formed in a cylindrical shape. The outflow inner circumferential surface 15c is provided with an outlet 19 to allow the fluid to flow out of the flow path 40. The outflow inner circumferential surface 15c defines the radially outer side of a space (an outflow region 40c, described later) in which the fluid is present before flowing out of the flow path 40.
The sealing inner circumferential surface 15d of the outer member 11 is located above the flow path 40 and extends upward from the upper end of the outflow inner circumferential surface 15c. In this embodiment, the sealing inner circumferential surface 15d is formed in a cylindrical shape extending continuously from the outflow inner circumferential surface 15c. The sealing inner circumferential surface 15d of the embodiment is in close proximity to or in contact with an outer circumferential surface 26a of an insertion portion 26 (described later) of the fixing member 12 and does not define the flow path 40. The fixing member 12 is provided with a sealing member 20 (e.g., an O-ring) (described later) which comes into contact with the sealing inner circumferential surface 15d. Thereby, the sealing inner circumferential surface 15d restricts the flow of the fluid upward from the flow path 40. In this embodiment, the fixing member 12 is provided with the sealing member 20; however, the embodiment is not so limited, and the sealing inner circumferential surface 15d of the outer member 11 may be provided with the sealing member 20.
As indicated by the dash-dot-dot line in
The fixing member 12 is fixed (e.g., fastened and secured) to the outer member 11. The fixing member 12 includes a lid portion 25 that closes the upper end opening 11a of the outer member 11 and the cylindrical insertion portion 26 that is inserted into the upper end opening 11a of the outer member 11 from above.
The lid portion 25 of the fixing member 12 is formed to have a larger diameter than the upper end opening 11a of the outer member 11. The lid portion 25 has a through hole that passes therethrough in the vertical (axial) direction at a predetermined position radially inside the cylindrical insertion portion 26 (in this embodiment, the center of the lid portion 25 centered on the central axis CL). The through hole is provided with a female threaded portion 27 formed in its inner circumferential surface. The lid portion 25 also has a rotation preventing pin 28 that extends along the axial direction and is fixed at a different position than the female threaded portion 27 radially inside the cylindrical insertion portion 26. The pin 28 is removably attached to the lid portion 25 and, when fixed to the lid portion 25, extends downward along the axial direction from the lower surface of the lid portion 25.
The cylindrical insertion portion 26 of the fixing member 12 has the outer circumferential surface 26a that is in close proximity to or in contact with the sealing inner circumferential surface 15d of the outer member 11 and faces the same, an inner circumferential surface 26b that slidably supports the inner member 13, and a lower surface 26c that defines the upper part of the flow path 40. The outer circumferential surface 26a of the insertion portion 26 is formed to have a circular cross section with a slightly smaller diameter than the sealing inner circumferential surface 15d of the outer member 11, and it faces the sealing inner circumferential surface 15d. The outer circumferential surface 26a of the insertion portion 26 is provided with the sealing member 20 (e.g., an O-ring). While in contact with the sealing inner circumferential surface 15d of the outer member 11 over the entire circumference, the sealing member 20 seals between the outer circumferential surface 26a of the insertion portion 26 and the sealing inner circumferential surface 15d and restricts the flow of the fluid upward from the flow path 40. The inner circumferential surface 26b of the insertion portion 26 is formed to have a circular cross section and is provided with a sealing member 29 (e.g., an O-ring). While in contact with the outer circumferential surface 16 of the inner member 13 over the entire circumference, the sealing member 29 seals between the inner circumferential surface 26b of the insertion portion 26 and the outer circumferential surface 16 and restricts the flow of the fluid upward from the flow path 40. In this embodiment, the fixing member 12 is provided with the sealing members 20 and 29; however, the embodiment is not so limited. The inner circumferential surface 15 of the outer member 11 may be provided with the sealing member 20, and the outer circumferential surface 16 of the inner member 13 may be provided with the sealing member 29.
The inner member 13 is located radially inside the outer member 11 (the internal space of the outer member 11) and is slidably supported by the fixing member 12. In other words, the inner member 13 is movable in the axial direction with respect to the outer member 11 through the fixing member 12. In this embodiment, the inner member 13 is inserted into the internal space of the outer member 11 from the upper end opening 11a of the outer member 11 while being supported by the fixing member 12. The inner member 13 has the outer circumferential surface 16 that defines the flow path 40 between it and the inner circumferential surface 15 of the outer member 11.
The inner member 13 of the embodiment is formed in a bottomed cylindrical shape with an opening at the top. The inner member 13 is provided with a supported portion 30 which is supported by the differential screw 14 in its internal space.
The supported portion 30 of the inner member 13 has a through hole that is coaxial with the female threaded portion 27 of the fixing member 12. The through hole is provided with a female threaded portion 31 formed in its inner circumferential surface. In this embodiment, the female threaded portion 31 of the through hole has a diameter smaller than that of the female threaded portion 27 of the fixing member 12. The female threaded portion 31 of the supported portion 30 has threads formed at a shorter pitch than the threads of the female threaded portion 27 of the fixing member 12. For example, the threads of the female threaded portion 31 of the supported portion 30 are formed at a pitch of 1.8 mm, while the threads of the female threaded portion 27 of the fixing member 12 are formed at a pitch of 2.0 mm. The supported portion 30 also has a pin insertion hole 32 through which the pin 28 of the fixing member 12 is inserted. The pin 28 passing through the pin insertion hole 32 allows the inner member 13 to move in the axial direction with respect to the fixing member 12 and restricts the rotation of the inner member 13 relative to the fixing member 12. Incidentally, the internal space of the inner member 13 may serve as a jacket through which the other fluids mentioned above can flow to adjust the temperature of the fluid to be treated (fluid) in the flow path 40. The fluid flowing through the jacket (internal space) of the inner member 13 may be the same fluid as that flowing through the jacket 21 of the outer member 11, or it may be a different fluid.
The outer circumferential surface 16 of the inner member 13 defines the radially inner side of the flow path 40 and includes three regions, one on top of another, each having a surface with a different function. In other words, the outer circumferential surface 16 of the inner member 13 includes three surfaces with different functions: a tapered outer circumferential surface 16a, an outflow outer circumferential surface 16b, and a sealing outer circumferential surface 16c, in this order from bottom to top. That is, the inner member 13 has the tapered outer circumferential surface 16a as a part of the outer circumferential surface 16.
The tapered outer circumferential surface 16a of the inner member 13 is a tapered (conical) surface and faces the tapered inner circumferential surface 15b of the outer member 11 in a state of being spaced radially inward from the tapered inner circumferential surface 15b. In this embodiment, the tapered outer circumferential surface 16a extends continuously from the vertex of the lower end of the inner member 13 such that its diameter increases upward. In other words, the tapered outer circumferential surface 16a of the embodiment is tapered from the top to the bottom. Thus, the dispersion region 40b (described later) of the flow path 40 is defined between the tapered outer circumferential surface 16a and the tapered inner circumferential surface 15b. In this embodiment, the inner member 13 is formed such that the vertex of the tapered profile of the tapered outer circumferential surface 16a corresponds to the lower end of the inner member 13. The vertex of the tapered profile of the tapered outer circumferential surface 16a is located on the central axis CL.
As illustrated in
The outflow outer circumferential surface 16b of the inner member 13 extends upward from the upper end of the tapered outer circumferential surface 16a. In this embodiment, the outflow outer circumferential surface 16b is formed in a cylindrical shape. The outflow outer circumferential surface 16b is located at a position spaced radially inward from the outflow inner circumferential surface 15c of the outer member 11 and defines a space (the outflow region 40c, described later) between it and the outflow inner circumferential surface 15c. The separation distance between the outflow outer circumferential surface 16b of the inner member 13 and the outflow inner circumferential surface 15c of the outer member 11 is set larger than the separation distance (clearance distance L1, described later) between the tapered outer circumferential surface 16a and the upper region 18 of the tapered inner circumferential surface 15b.
The sealing outer circumferential surface 16c of the inner member 13 is located above the flow path 40 and extends upward from the outflow outer circumferential surface 16b. In this embodiment, the sealing outer circumferential surface 16c is formed in a cylindrical shape extending continuously from the outflow outer circumferential surface 16b. The sealing outer circumferential surface 16c is formed to have a slightly smaller diameter than the inner circumferential surface 26b of the insertion portion 26 of the fixing member 12, and it faces the inner circumferential surface 26b. The sealing outer circumferential surface 16c is in close proximity to or in contact with the inner circumferential surface 26b of the insertion portion 26 of the fixing member 12 and does not define the flow path 40. The sealing member 29 on the inner circumferential surface 26b of the insertion portion 26 of the fixing member 12 comes into contact with the sealing outer circumferential surface 16c. While in contact with the sealing outer circumferential surface 16c of the inner member 13 over the entire circumference, the sealing member 29 restricts the flow of the fluid upward from the flow path 40.
The differential screw 14 is a member that allows the separation distance (hereinafter referred to as “clearance distance”) between the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a to be adjusted by moving the inner member 13 with respect to the outer member 11. The differential screw 14 integrally includes a shaft 14a and a handle 14b.
The shaft 14a of the differential screw 14 extends linearly in the axial direction and is inserted through the through hole of the fixing member 12 having the female threaded portion 27 formed therein and the through hole of the inner member 13 having the female threaded portion 31 formed therein. The upper end of the shaft 14a protrudes upward from the lid portion 25 of the fixing member 12. The shaft 14a has a first male threaded portion 33 that is threaded into the female threaded portion 27 of the fixing member 12 and a second male threaded portion 34 that is threaded into the female threaded portion 31 of the inner member 13. In this embodiment, the first male threaded portion 33 is formed to have a larger diameter than the second male threaded portion 34. The pitch of the threads of the first male threaded portion 33 is set longer than the pitch of the threads of the second male threaded portion 34. For example, the threads of the first male threaded portion 33 are formed at a pitch of 2.0 mm, while the threads of the second male threaded portion 34 are formed at a pitch of 1.8 mm. Thus, when the differential screw 14 is turned once, the inner member 13 slides 0.2 mm in the axial direction with respect to the outer member 11. In this embodiment, the supported portion 30 of the inner member 13 is provided with the female threaded portion 31, and the differential screw 14 is provided with the second male threaded portion 34; however, the embodiment is not so limited. For example, the supported portion 30 of the inner member 13 may be provided with a male threaded portion in place of the female threaded portion 31, while the differential screw 14 may be provided with a female threaded portion that is threaded with the male threaded portion in place of the second male threaded portion 34.
The handle 14b of the differential screw 14 includes an arm 35 extending radially outward from the upper end of the shaft 14a and an operating portion 36 extending upward in the axial direction from the distal end of the arm 35. The user can slide the inner member 13 in the axial direction with respect to the outer member 11 by, for example, gripping the operating portion 36 and rotating the handle 14b to rotate the shaft 14a.
Next, the assembly of the disperser 10 will be described. To assemble the disperser 10, first, the differential screw 14 and the inner member 13 are assembled to the fixing member 12. Next, the inner member 13 assembled to the fixing member 12 is inserted into the upper end opening 11a of the outer member 11 from the tapered outer circumferential surface 16a side. The insertion portion 26 of the fixing member 12 is then inserted into the upper end opening 11a of the outer member 11, and the lid portion 25 of the fixing member 12 is fixed to the outer member 11. In this manner, the outer member 11, the fixing member 12, the inner member 13, and the differential screw 14 can be assembled into the disperser 10. In the process of assembling the disperser 10, the clearance between the tapered outer circumferential surface 16a and the tapered inner circumferential surface 15b can be adjusted. The adjustment of the clearance distance will be described later.
A description will then be given of the flow path 40 defined between the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13.
When the disperser 10 is assembled, the flow path 40 is defined between the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13, through which the fluid to be treated flows from the lower side to the upper side. The flow path 40 of the embodiment includes three regions having different shapes and functions. Specifically, the flow path 40 includes three regions: the inflow region 40a, the dispersion region 40b, and the outflow region 40c, in this order from bottom to top.
The inflow region 40a of the flow path 40 is a space through which the fluid to be treated flowing into the flow path 40 first passes, and it is defined by the inflow inner circumferential surface 15a of the outer member 11. The lower end opening 11b of the outer member 11 communicates with the inflow region 40a of the flow path 40.
The dispersion region 40b of the flow path 40 is a region where the fluid to be treated can be dispersed. The dispersion region 40b is defined between the tapered outer circumferential surface 16a of the inner member 13 and the tapered inner circumferential surface 15b of the outer member 11. The dispersion region 40b extends upward continuously from the inflow region 40a. In this embodiment, the dispersion region 40b increases in diameter from the lower side to the upper side.
The dispersion region 40b of the flow path 40 includes: a reduction region 40ba defined between the lower region 17 of the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a; and a constant region 40bb defined between the upper region 18 of the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a (see
In the constant region 40bb of the dispersion region 40b, the clearance distance L1 is preferably 0.1 μm or more and 2 mm or less. When the clearance distance L1 is set within the above range, a large shear force can be efficiently applied to the fluid to be treated to disperse it. In addition, the length L2 (see
The outflow region 40c of the flow path 40 is a space where the fluid to be treated that has passed through the dispersion region 40b flows in, and it is defined between the outflow inner circumferential surface 15c of the outer member 11 and the outflow outer circumferential surface 16b of the inner member 13. The outflow region 40c is located above the dispersion region 40b and communicates with the dispersion region 40b. The upper part of the outflow region 40c is defined by the lower surface 26c of the insertion portion 26 of the fixing member 12. The separation distance between the outflow inner circumferential surface 15c and the outflow outer circumferential surface 16b in the outflow region 40c is set larger than the clearance distance L1 in the constant region 40bb of the dispersion region 40b.
In this embodiment, when the axial direction corresponds to the vertical direction, the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13 have no horizontal portion where fluid flowing through the flow path 40 may accumulate. Specifically, the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13 do not have a horizontal upper surface when the axial direction corresponds to the vertical direction.
The material for the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13 may be selected from metal or the like as appropriate, depending on the type of fluid to be treated. For example, the material may be SUS316L that has been buffed and then electrolytically polished. Although it is preferred that the regions of the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13 that define the constant region 40bb of the dispersion region 40b of the flow path 40 be made of ceramic such as silicon carbide, tungsten carbide, or alumina to prevent seizure, diamond-like carbon or the like may be used instead. In addition, it is preferred that the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13, which define the flow path 40, be coated with a corrosion-resistant material. Examples of coatings made of corrosion-resistant materials include glass-lined coatings, fluoropolymer coatings, and ceramic coatings; fluoropolymer coatings are preferred.
Next, a description will be given of the flow of the fluid to be treated when the disperser 10 performs a dispersion process or the like.
As indicated by the white arrow in
Having flowed into the dispersion region 40b, the fluid first flows through the reduction region 40ba of the dispersion region 40b. In the reduction region 40ba, the fluid moves upward along the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a. In the reduction region 40ba, the clearance distance gradually decreases toward the upper side, and the fluid gradually changes its flow direction from the axial direction to the circumferential direction while maintaining the pressure and flows into the constant region 40bb located above. After flowing into the constant region 40bb, the fluid is subjected to a shear force due to the clearance distance L1 set appropriately and is thereby dispersed. The fluid, which has maintained the pressure in the dispersion region 40b, flows into the outflow region 40c located above.
After flowing into the outflow region 40c, the fluid is released under low pressure in the outflow region 40c. As a result, a portion of the fluid evaporates to cause flash steam, and cavitation also occurs. The flash steam and cavitation apply a shear force to the fluid to disperse it. In other words, the fluid, which has maintained the pressure in the dispersion region 40b, is further dispersed as it is released under low pressure in the outflow region 40c. The dispersed material flows out of the disperser 10 from the outlet 19 of the outflow region 40c.
Next, a method of using the disperser 10 will be described.
First, it will be described how to adjust the clearance distance L1 in the constant region 40bb of the flow path 40 to place the disperser 10 in the use state, and then how to clean or sterilize the disperser 10.
To adjust the clearance distance L1 in the constant region 40bb of the flow path 40, first, the differential screw 14 is rotated to slide the inner member 13 downward along the axial direction with respect to the outer member 11 so that the disperser 10 is brought into the contact state where the tapered outer circumferential surface 16a of the inner member 13 and the upper region 18 of the tapered inner circumferential surface 15b of the outer member 11 are in contact with each other (clearance distance L1=0) (see
To clean or sterilize the disperser 10, the differential screw 14 is further rotated to bring the disperser 10 from the use state into the separate state where the clearance distance is further apart than in the used state (see
As described above, the disperser 10 can be brought into the contact state where the tapered outer circumferential surface 16a and the tapered inner circumferential surface 15b are in contact with each other (see
In the disperser 10 configured as described above, the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a are formed such that the angle of one with respect to the other in the axial cross section changes in the middle of the dispersion region 40b. As a result, the dispersion region 40b of the flow path 40 has portions where the clearance distance between the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a varies in different manners (in this embodiment, the reduction region 40ba and the constant region 40bb). For example, by virtue of the reduction region 40ba provided in the dispersion region 40b, the flow direction of the fluid to be treated can be gradually changed from the axial direction to the circumferential direction. Additionally, by virtue of the constant region 40bb provided in the dispersion region 40b, when the clearance distance L1 is set appropriately, a large shear force can be efficiently applied to the fluid to be treated to disperse it, and a finely dispersed material (e.g., nanoparticles) can be obtained.
In addition, after flowing into the outflow region 40c from the dispersion region 40b, the fluid to be treated is released under low pressure, which causes flash steam and cavitation. The flash steam and cavitation apply a shear force to the fluid to disperse it, and the fluid can be further dispersed.
Moreover, the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a define the flow path 40. Therefore, in contrast to the case where one of them is a non-tapered surface (e.g., a cylindrical surface extending along the axial direction), the clearance distance can be adjusted by moving the outer member 11 and the inner member 13 in the axial direction relative to each other.
Further, the clearance distance can be finely adjusted as it is adjusted by using the differential screw 14. Thus, the clearance distance can be set appropriately to efficiently apply a large shear force to the fluid to be treated to disperse it, and a finely dispersed material (e.g., nanoparticles) can be obtained.
Furthermore, when the axial direction (predetermined direction) corresponds to the vertical direction, the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13 have no horizontal portion where fluid flowing through the flow path 40 may accumulate. This prevents any cleaning agent (condensed water of pure steam, etc.) from remaining in the flow path 40 at the time of cleaning, for example, the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13.
While the fluid to be treated is being dispersed, the outer member 11 and the inner member 13 are not moved relative to each other. Therefore, in contrast to the case where the outer member and the inner member are rotated relative to each other during the dispersion process, a finely dispersed material can be obtained from the fluid with low power.
As described above, while the fluid to be treated is being dispersed, the outer member 11 and the inner member 13 are not moved relative to each other. That is, the outer member 11 and the inner member 13 have no sliding parts that slide against each other during use. Therefore, it is possible to simplify the structure and suppress the generation of foreign substances. Since the disperser 10 can suppress the generation of foreign substances and can be cleaned and sterilized in place as described above, it can be used for pharmaceutical manufacturing equipment (in particular, injection manufacturing equipment).
Specifically, the processes of producing pharmaceuticals, cosmetics, food, chemical products, electronic components, and the like often include a dispersion process that produces fine particles such as nanocrystals, nanoemulsions, liposomes, and nanospheres. There are various requirements for a disperser that enables the production of such fine particles, especially nanoparticles. For example, a disperser used to produce vaccines such as new coronavirus vaccines must be cleaned and sterilized in place without disassembling its parts to eliminate human error, because the vaccines are injections. In addition, since pure steam or the like flows through the flow path 40 during sterilization, thermal countermeasures are required for the inner circumferential surface 15 of the outer member 11 and the outer circumferential surface 16 of the inner member 13 that define the flow path 40. There is also a need to drain condensed water of pure steam without leaving residue. As described above, the disperser 10 of the present disclosure can satisfy these requirements.
It is also required to reliably prevent foreign substances (e.g., foreign substances generated from sliding parts, etc.) from mixing with the finely dispersed material. For this reason, it is difficult to use a dispersing device such as a bead mill or an ultrasonic oscillator. In a bead mill, foreign substances such as bead fragments and wear debris may be generated and mixed into the material being treated. In an ultrasonic disperser, erosion occurs due to cavitation, resulting in the generation of foreign substances, which may be mixed into the material being treated. As described above, the disperser 10 of the present disclosure can satisfy these requirements.
Incidentally, manufacturers of pharmaceuticals and similar products are required to perform validation to verify that their pharmaceuticals and medical devices are manufactured using the correct processes and methods. As described above, the disperser 10 of the present disclosure can satisfy various requirements for a disperser used in the production of pharmaceutical products or the like, and therefore it can also satisfy requirements for validation.
In addition, the sealing member 29 seals between the sealing outer circumferential surface 16c of the inner member 13 and the inner circumferential surface 26b of the insertion portion 26 of the fixing member 12. Thus, dust and the like can be prevented from entering the fluid to be treated in the flow path 40 from the internal space of the inner member 13 in which the differential screw 14 and the like are located.
As described above, according to the embodiment, shear force can be efficiently applied to a material to be treated with low power to produce fine particles, particularly nanoparticles.
According to the embodiment, the tapered inner circumferential surface 15b of the outer member 11 has two regions (the lower region 17 and the upper region 18) with different taper angles, while the tapered outer circumferential surface 16a of the inner member 13 has a constant taper angle from the upper end to the lower end, thereby providing the dispersion region 40b of the flow path 40 with the reduction region 40ba and the constant region 40bb; however, the embodiment is not so limited. For example, as illustrated in
According to the embodiment, the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a are formed such that the angle of one with respect to the other in the axial cross section changes in the middle of the dispersion region 40b, and they form two different angles; however, the embodiment is not so limited. The tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a only need to form at least two different angles in the axial cross section, and they may form three or more different angles.
According to the embodiment, the dispersion region 40b of the flow path 40 is provided with the constant region 40bb where the clearance distance is constant; however, the embodiment is not so limited. The tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a only need to be formed such that the angle of one with respect to the other changes to a different angle in the middle of the dispersion region 40b.
According to the embodiment, one of the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a has a taper angle which changes at a predetermined height position in the axial cross section, and the other has a taper angle which is constant from the upper end to the lower end; however, the embodiment is not so limited. For example, the taper angles of both the tapered inner circumferential surface 15b and the tapered outer circumferential surface 16a may be changed at a predetermined height position so that the dispersion region 40b of the flow path 40 is provided with portions where the clearance distance varies in different manners.
According to the embodiment, the disperser 10 includes the fixing member 12 that is fixed to the outer member 11 and slidably supports the inner member 13 and the differential screw 14 that slides the inner member 13 with respect to the fixing member 12, and the fixing member 12 and the differential screw 14 are designed to function as clearance adjustment parts; however, the clearance adjustment parts are not limited to them. For example, as illustrated in
Additionally, as illustrated in
A second embodiment of the present invention will be described below with reference to the accompanying drawings. A disperser 70 of this embodiment differs from that of the first embodiment in that its tapered inner circumferential surface 75c and tapered outer circumferential surface 76c are tapered from the bottom to the top. Like parts or elements as those in the first embodiment will be designated by like reference numerals, and the description thereof will be omitted.
As illustrated in
The outer member 71 and the inner member 73 are concentrically arranged so that their central axes CL coincide. There is a gap (space) between an inner circumferential surface 75 of the outer member 71 and an outer circumferential surface 76 of the inner member 73, and the gap serves as the flow path 40 through which a fluid to be treated flows. The flow path 40 allows the fluid to be treated to flow from the lower side (one side in the predetermined direction) to the upper side (the other side in the predetermined direction). Unless otherwise specified, the following describes the structure of the disperser 70 in the use state.
The outer member 71 is formed in a cylindrical shape whose central axis CL extends in a predetermined direction (the vertical direction in this embodiment). The outer member 71 has an upper end opening 71a at the upper end, a lower end opening 71b at the lower end, and the inner circumferential surface 75 extending between the upper end opening 71a and the lower end opening 71b. The upper end opening 71a and the lower end opening 71b are arranged to be concentric with the central axis CL. In this embodiment, the upper end opening 71a is formed to have a smaller diameter than the lower end opening 71b. The lower end opening 71b of the outer member 71 serves as an insertion port for inserting the inner member 73 into the outer member 71.
The inner circumferential surface 75 of the outer member 71 includes four regions, one on top of another, each having a surface with a different function. In other words, the inner circumferential surface 75 of the outer member 71 includes four surfaces with different functions: a sealing inner circumferential surface 75a, an inflow inner circumferential surface 75b, the tapered inner circumferential surface 75c, and an outflow inner circumferential surface 75d, in this order from bottom to top. That is, the outer member 71 has the tapered inner circumferential surface 75c as a part of the inner circumferential surface 75. The inflow inner circumferential surface 75b, the tapered inner circumferential surface 75c, and the outflow inner circumferential surface 75d of the outer member 71 define the radially outer side of the flow path 40.
The sealing inner circumferential surface 75a of the outer member 71 is located below the flow path 40 and extends upward from the lower end opening 71b of the outer member 71. In this embodiment, the sealing inner circumferential surface 75a is formed in a cylindrical shape extending continuously from the lower end opening 71b of the outer member 71. The sealing inner circumferential surface 75a of the embodiment is in close proximity to or in contact with the outer circumferential surface 26a of the insertion portion 26 of the fixing member 72 (described later) and does not define the flow path 40. The fixing member 72 is provided with the sealing member 20 (e.g., an O-ring) which comes into contact with the sealing inner circumferential surface 75a. Thereby, the sealing inner circumferential surface 75a restricts the flow of the fluid downward from the flow path 40. In this embodiment, the fixing member 72 is provided with the sealing member 20; however, the embodiment is not so limited, and the sealing inner circumferential surface 75a of the outer member 71 may be provided with the sealing member 20.
The inflow inner circumferential surface 75b of the outer member 71 is located below the tapered inner circumferential surface 75c and extends continuously from the upper end of the sealing inner circumferential surface 75a to the lower end of the tapered inner circumferential surface 75c. In this embodiment, the inflow inner circumferential surface 75b is formed in a cylindrical shape. The inflow inner circumferential surface 75b defines the radially outer side of the inflow region 40a into which the fluid to be treated first flows. The inflow inner circumferential surface 75b is provided with an inlet 77 for the fluid to be treated. The inlet 77 is connected to a supply source (not illustrated) for pumping the fluid to be treated and allows the fluid to flow into the flow path 40. In this embodiment, the supply source (not illustrated) pumps the fluid to be treated from the inlet 77 into the flow path 40 at a pressure of 0.5 MPaG.
The tapered inner circumferential surface 75c of the outer member 71 is a tapered (conical) surface and extends upward continuously from the inflow inner circumferential surface 75b. In this embodiment, the tapered inner circumferential surface 75c is tapered from the bottom to the top. The tapered inner circumferential surface 75c defines the radially outer side of a space (the dispersion region 40b) in which the fluid to be treated can be dispersed. The vertex (not illustrated) of the tapered profile of the tapered inner circumferential surface 75c is located on the central axis CL.
In this embodiment, the tapered inner circumferential surface 75c has two regions with different taper angles: an upper region and a lower region. Specifically, the tapered inner circumferential surface 75c has a lower region 78 with a larger taper angle and an upper region 79 with a taper angle smaller than that of the lower region 78. The upper region 79 extends upward from the upper end of the lower region 78 (the lower end of the upper region 79). In other words, the taper angle of the tapered inner circumferential surface 75c changes at a predetermined height position in the middle of the tapered inner circumferential surface 75c.
The outflow inner circumferential surface 75d of the outer member 71 extends continuously from the upper end of the tapered inner circumferential surface 75c to the upper end opening 71a of the outer member 71 located above. In this embodiment, the outflow inner circumferential surface 75d is formed in a cylindrical shape. The outflow inner circumferential surface 75d defines the radially outer side of a space (the outflow region 40c) in which the fluid is present before flowing out of the flow path 40. The diameter of the outflow region 40c is set larger than the separation distance (clearance distance L1) between the upper region 79 of the tapered inner circumferential surface 75c and the tapered outer circumferential surface 76c (described later) of the inner member 73. The upper end opening 71a of the outer member 71 serves as an outlet through which the fluid flows out of the flow path 40.
The fixing member 72 is fixed (e.g., fastened and secured) to the outer member 71. The fixing member 72 includes a lid portion 80 that closes the lower end opening 71b of the outer member 71 and a cylindrical insertion portion 81 that is inserted into the lower end opening 71b of the outer member 71 from below. Note that the lid portion 80 and the insertion portion 81 of the fixing member 72 have substantially the same configuration as the lid portion 25 and the insertion portion 26 of the fixing member 12 of the first embodiment, and therefore the description thereof will not be repeated.
The inner member 73 is located radially inside the outer member 71 (the internal space of the outer member 71) and is slidably supported by the fixing member 72. In other words, the inner member 73 is movable in the axial direction with respect to the outer member 71 through the fixing member 72. In this embodiment, the inner member 73 is inserted into the internal space of the outer member 71 from the lower end opening 71b of the outer member 71 while being supported by the fixing member 72. The inner member 73 has the outer circumferential surface 76 that defines the flow path 40 between it and the inner circumferential surface 75 of the outer member 71.
The inner member 73 of the embodiment is formed in a bottomed cylindrical shape with an opening at the bottom. The inner member 73 is provided with the supported portion 30 which is supported by the differential screw 74 in its internal space.
The outer circumferential surface 76 of the inner member 73 defines the radially inner side of the flow path 40 and includes three regions, one on top of another, each having a surface with a different function. In other words, the outer circumferential surface 76 of the inner member 73 includes three surfaces with different functions: a sealing outer circumferential surface 76a, an inflow outer circumferential surface 76b, and the tapered outer circumferential surface 76c, in this order from bottom to top. That is, the inner member 73 has the tapered outer circumferential surface 76c as a part of the outer circumferential surface 76.
The sealing outer circumferential surface 76a of the inner member 73 is located below the flow path 40 and extends upward from the lower end of the inner member 73. In this embodiment, the sealing outer circumferential surface 76a is formed in a cylindrical shape. The sealing outer circumferential surface 76a is formed to have a slightly smaller diameter than the inner circumferential surface of the insertion portion 81 of the fixing member 72, and it faces the inner circumferential surface of the insertion portion 81. The sealing outer circumferential surface 76a is in close proximity to or in contact with the inner circumferential surface of the insertion portion 81 of the fixing member 72 and does not define the flow path 40. The sealing member 29 on the inner circumferential surface of the insertion portion 81 of the fixing member 72 comes into contact with the sealing outer circumferential surface 76a. While in contact with the sealing outer circumferential surface 76a of the inner member 73 over the entire circumference, the sealing member 29 restricts the flow of the fluid downward from the flow path 40.
The inflow outer circumferential surface 76b of the inner member 73 extends upward from the upper end of the sealing outer circumferential surface 76a. In this embodiment, the inflow outer circumferential surface 76b is formed in a cylindrical shape. The inflow outer circumferential surface 76b is located at a position spaced radially inward from the inflow inner circumferential surface 75b of the outer member 71 and defines a space (the inflow region 40a) between it and the inflow inner circumferential surface 75b.
The tapered outer circumferential surface 76c of the inner member 73 is a tapered (conical) surface and faces the tapered inner circumferential surface 75c of the outer member 71 in a state of being spaced radially inward from the tapered inner circumferential surface 75c. In this embodiment, the tapered outer circumferential surface 76c extends continuously from the vertex of the upper end of the inner member 73 such that its diameter increases downward. In other words, the tapered outer circumferential surface 76c of the embodiment is tapered from the bottom to the top. Thus, the dispersion region 40b of the flow path 40 is defined between the tapered outer circumferential surface 76c and the tapered inner circumferential surface 75c. In this embodiment, the inner member 73 is formed such that the vertex of the tapered profile of the tapered outer circumferential surface 76c corresponds to the upper end of the inner member 73. The vertex of the tapered profile of the tapered outer circumferential surface 76c is located on the central axis CL.
In this embodiment, the taper angle of the tapered outer circumferential surface 76c is set to be constant from the upper end to the lower end, differently from the tapered inner circumferential surface 75c. The taper angle of the tapered outer circumferential surface 76c is set to be the same as the taper angle of the upper region 79 of the tapered inner circumferential surface 75c.
The differential screw 74 is a member that allows the clearance distance between the tapered inner circumferential surface 75c and the tapered outer circumferential surface 76c to be adjusted by moving the inner member 73 with respect to the outer member 71. The differential screw 74 integrally includes a shaft 74a and a handle 74b. Note that the shaft 74a and the handle 74b have substantially the same configuration as the shaft 14a and the handle 14b of the differential screw 14 of the first embodiment, and therefore the description thereof will not be repeated.
In this embodiment, the dispersion region 40b of the flow path 40 decreases in diameter from the bottom to the top.
The disperser 70 configured as described above achieves the same effects as the disperser 10 of the first embodiment. That is, according to the embodiment, shear force can be efficiently applied to a material to be treated with low power to produce fine particles, particularly nanoparticles.
While preferred embodiments of the invention have been described and illustrated, the invention is not limited to the embodiments disclosed herein. Various changes, modifications, and alterations may be made within the scope of the invention as defined in the appended claims. That is, many variations and modifications thereof may be made by those skilled in the art without departing from the spirit and scope of the invention. All such variations and modifications are intended to be included within the scope of the invention as defined in the appended claims.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2022/030382 | 8/9/2022 | WO |
