CN108608600B - Particle forming device and particle forming method thereof - Google Patents

Particle forming device and particle forming method thereof Download PDF

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Publication number
CN108608600B
CN108608600B CN201611125131.8A CN201611125131A CN108608600B CN 108608600 B CN108608600 B CN 108608600B CN 201611125131 A CN201611125131 A CN 201611125131A CN 108608600 B CN108608600 B CN 108608600B
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Prior art keywords
fluid
particle
spray head
layer
sleeve
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CN201611125131.8A
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CN108608600A (en
Inventor
洪正翰
刘宗鑫
林英杰
蔡銘芳
邹海清
林秋丰
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Metal Industries Research and Development Centre
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Metal Industries Research and Development Centre
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B9/00—Making granules
    • B29B9/10—Making granules by moulding the material, i.e. treating it in the molten state
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
    • B01J2/06—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a liquid medium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B9/00—Making granules
    • B29B9/12—Making granules characterised by structure or composition
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29B—PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
    • B29B9/00—Making granules
    • B29B9/12—Making granules characterised by structure or composition
    • B29B2009/125—Micropellets, microgranules, microparticles

Abstract

A particle spray head, a particle forming device and a particle forming method thereof are used for mass production of particles used as micro carriers, and the problem that the mass production of particles is not easy in the prior art is solved, the particle spray head comprises: the spray head comprises a spray head body, a first flow channel is arranged in the spray head body, one end of the first flow channel is connected with a plurality of extension pipes, the extension pipes are arranged at intervals, and one end of each extension pipe, which is far away from the first flow channel, forms an outflow port; the cover body is provided with a second flow passage, one end of the second flow passage is connected with a plurality of sleeves, and one end of each sleeve, which is far away from the second flow passage, forms an opening; the plurality of extension pipes respectively extend into the sleeves, and the outflow port of each extension pipe is positioned between the second flow passage and the opening of each sleeve.

Description

Particle forming device and particle forming method thereof
Technical Field
The present invention relates to a particle spray head, a particle forming apparatus and a particle forming method thereof, and more particularly, to a particle forming apparatus and a particle forming method thereof for mass-producing double-layered particles as microcarriers.
Background
Microparticles (microspheres), also known as microspheres (microspheres), generally refer to small spherical particles with a particle size of 1-1000 μm, are often used as microcarriers for drug release, and become one of the emerging drug delivery technologies due to their targeting, controlled release, stability, and surface modifiability.
How to form microparticles with uniform particle size, which is the primary goal of forming microparticles, is to have consistent drug release effect per microparticle due to the smaller particle size of the microparticles; for example, by forming fine particles by using the conventional micro flow channel structure 9 shown in FIG. 1, fine particles having a uniform particle size can be formed.
Referring to fig. 1, the conventional micro flow channel structure 9 includes a Y-branch flow channel 91, a curing agent injection hole 92, a material solution injection hole 93 and a cross-shaped micro flow channel 94, the Y-branch flow channel 91 is connected to the cross-shaped micro flow channel 94, wherein a branch flow channel of the Y-branch flow channel 91 is communicated with the curing agent injection hole 92, the curing agent injection hole 92 can be used for injecting a curing agent, another branch flow channel of the Y-branch flow channel 91 is communicated with the material solution injection hole 93 for injecting a material solution, the curing agent and the material solution form a pre-cured mixed solution at a third end, and the third end is communicated with the cross-shaped micro flow channel 94; in addition, an aqueous solution is injected from two ends of the cross-shaped microchannel 94, and the shear stress of the aqueous solution injected into the cross-shaped microchannel 94 causes the pre-solidified mixed solution flowing into the cross-shaped microchannel 94 to form separate latex spheres, which are finally formed into a particle.
Although the above-mentioned conventional micro flow channel structure 9 can form fine particles having a uniform particle diameter, the conventional micro flow channel structure 9 has a disadvantage that mass production is not easy, and thus there is a need for improvement.
Disclosure of Invention
In order to solve the above problems, the present invention provides a fine particle spray head, a fine particle forming apparatus and a fine particle forming method thereof, which are used for mass production of double-layer fine particles with uniform particle size.
A particle spray head of the present invention comprises: the spray head comprises a spray head body, a first flow channel is arranged in the spray head body, one end of the first flow channel is connected with a plurality of extension pipes, the extension pipes are arranged at intervals, and one end of each extension pipe, which is far away from the first flow channel, forms an outflow port; the cover body is provided with a second flow passage, one end of the second flow passage is connected with a plurality of sleeves, and one end of each sleeve, which is far away from the second flow passage, forms an opening; the plurality of extension pipes respectively extend into the sleeves, and the outflow port of each extension pipe is positioned between the second flow passage and the opening of each sleeve.
Wherein, these extension pipes and these sleeve pipes parallel arrangement. Therefore, each extension pipe can be aligned with each sleeve pipe respectively, so that each extension pipe can extend into each sleeve pipe respectively.
The second flow passage is formed between the cover body and the spray head body, and the plurality of extension pipes of the spray head body penetrate through the second flow passage, so that the plurality of extension pipes can respectively extend into the sleeves of the cover body.
Wherein each sleeve forms a forming space between the opening and the outflow opening of each extension pipe. Therefore, the forming space can ensure that the second fluid completely covers the first fluid flowing out from the outflow port at the opening.
Wherein, one end of each sleeve pipe with the opening is provided with a layer of hydrophobic material. Therefore, the fluid can contact the hydrophobic material layer when flowing out through the openings, so that the fluid is not easy to adhere to the sleeves, the fluid is prevented from accumulating at the outflow openings, and the influence of the surface tension on the particle size of a formed finished product is reduced.
The particle forming apparatus of the present invention is provided with the particle spray head as described above, and further includes: the extension pipe of the spray head body extends into the containing groove; the fluid cut-off device is arranged on the containing groove and can drive the fluid loaded in the containing groove to generate disturbance; and the accommodating groove is arranged in the temperature control system.
The container is used for loading a third fluid, the liquid level of the third fluid is a liquid level height, the opening of each sleeve is positioned below the liquid level height, and the outflow port of each extension pipe is positioned below the liquid level height, so that the opening of each sleeve is positioned in the third fluid.
Wherein, still be equipped with a collecting vat, and should hold the groove and be equipped with an inlet tube and an outlet pipe, this inlet tube and this outlet pipe run through this appearance groove outer wall, and this collecting vat intercommunication should hold the outlet pipe of groove. Therefore, the third fluid in the containing groove and the particle semi-finished product flow to the collecting groove through the outlet pipe, so that a worker can collect the particle semi-finished product by using the collecting groove; and the inflow port can be used for injecting the third fluid so as to keep the third fluid in the containing groove to have the liquid level height, thereby ensuring that the opening of each sleeve is positioned in the third fluid.
Wherein, the fluid cut-off device comprises a stirring device arranged in the containing groove. Therefore, the stirring device can drive the third fluid to flow so as to cut the double-layer continuous fluid flowing out of each opening of the cover body by utilizing the shearing force when the third fluid flows.
Wherein, the fluid cut-off device comprises an ultrasonic generator combined with the outer wall of the containing groove. Therefore, the ultrasonic generator can make the third fluid generate vibration to break the double-layer continuous fluid flowing out from each opening of the cover body.
A particle forming method of the present invention, which can be performed using the particle forming apparatus as described above, includes: loading a third fluid into the vessel such that the openings of the sleeves are located in the third fluid; introducing a first fluid into a first flow channel of the spray head body, enabling the first fluid to flow through the extension pipe at a first flow rate, introducing a second fluid into the sleeve of the cover body, enabling the second fluid to flow through the sleeve at a second flow rate, wherein the second flow rate is greater than the first flow rate, and enabling the second fluid to coat the first fluid flowing out from the outflow port of the extension pipe so as to form a double-layer continuous fluid flowing out through the openings of the sleeves; driving the fluid cut-off device to generate disturbance on the third fluid, including driving the stirring device to rotate to drive the third fluid to flow, and/or starting the ultrasonic generator to vibrate the third fluid, so that the double-layer continuous fluid forms a semi-finished product of particles in the containing groove; collecting the particulate intermediates, the particulate intermediates including an inner layer formed by the first fluid, an intermediate layer formed by the second fluid, and an outer layer formed by the third fluid; and removing the outer layer of the particle semi-finished product.
The second fluid heats the biodegradable high molecular material to the glass transition temperature, so that the second fluid can be introduced into the first flow channel of the nozzle body.
Wherein the temperature control system is activated to maintain the third fluid at a predetermined temperature that is equal to or less than the glass transition temperature of the second fluid prior to passing the second fluid into the second flow channel. Therefore, when the first fluid and the second fluid form double-layer micro-droplets, the temperature of the third fluid can assist the double-layer micro-droplets in solidification and shaping.
The second fluid is prepared by adding biodegradable high polymer material into organic solvent, so that the second fluid can be introduced into the first flow channel of the nozzle body.
Wherein the first fluid is a liquid having a pharmaceutical composition. Therefore, when the double-layer particle product formed by the first fluid and the second fluid is administered to an organism, the effect of slowly releasing the medicinal components can be achieved through the coating of the second fluid.
The first fluid is a gas, so as to form a double-layer particle finished product comprising a gaseous inner layer formed by the first fluid.
The third fluid is a stabilizer which can be a polyvinyl alcohol solution with the concentration of 1-15%, so that the plurality of particle semi-finished products can be processed by a drying method, or the particle semi-finished products are washed by an aqueous solution to remove the outer layer of the particle semi-finished products, and the inner layer and the middle layer of the particle semi-finished products are formed into double-layer particle finished products.
The invention has the beneficial effects that:
by the particle spray head, the particle forming device and the particle forming method, double-layer continuous fluid is generated by the spray head body and the cover body of the particle spray head, and the double-layer continuous fluid is broken by utilizing the shearing force and/or vibration of the third fluid, so that double-layer particles with uniform particle size can be produced in large quantity, the process time for forming the double-layer particles can be shortened, and the effect of improving the particle production efficiency is achieved.
Drawings
The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.
FIG. 1: schematic diagram of the existing micro flow channel structure;
FIG. 2: an exploded perspective view of a particle spray head of one embodiment of the present invention;
FIG. 3: an assembled cross-sectional view of a particle spray head of one embodiment of the present invention;
FIG. 4: an assembled cross-sectional view of a particulate forming apparatus of an embodiment of the present invention;
FIG. 5: an enlarged partial cross-sectional view of a particulate forming apparatus according to an embodiment of the present invention;
FIG. 6: an enlarged partial cross-sectional view of a particle spray head of one embodiment of the present invention;
FIG. 7: a schematic view of a semi-finished product of fine particles obtained by a fine particle forming apparatus according to an embodiment of the present invention;
FIG. 8: a schematic diagram of a double-layer particle product produced by the particle forming apparatus according to an embodiment of the present invention;
FIG. 9: the particulate forming apparatus of one embodiment of the present invention is provided with a combined cross-sectional view of a collecting tank;
FIG. 10: an assembled sectional view of a particulate forming apparatus according to another embodiment of the present invention;
FIG. 11: the particle forming apparatus of one embodiment of the present invention can be used to produce a double-layered particle product with a gaseous inner layer.
Description of the reference numerals
1 particle spray head
11 spray head body 111 first flow channel
112 extended pipe 113 outflow port
12 cover 121 second flow path
122 opening of sleeve 123
124 forming space
2 containing groove
21 liquid level and 22 bottom
23 inlet pipe 24 outlet pipe
3 fluid cut-off device
31 stirring device 32 ultrasonic generator
4 temperature control system
5 collecting tank
F1 first fluid F2 second fluid
F3 third fluid
v1 first flow velocity v2 second flow velocity
Semi-finished product of S particles
Inner layer of S1 intermediate layer of S2
S3 outer layer
M double-layer particle finished product
M1 inner layer M2 outer layer
M' double-layer particle finished product
M1 'inner layer M2' outer layer
[ Prior Art ]
9 existing micro-channel structure
91Y-type branched runner 92 curing agent injection hole
93 material solution is injected into the cross-shaped microchannel 94.
Detailed Description
In order to make the aforementioned and other objects, features and advantages of the present invention comprehensible, preferred embodiments accompanied with figures are described in detail below:
referring to fig. 2 and 3, a particle spray head 1 according to an embodiment of the present invention includes a spray head body 11 and a cover 12, wherein the cover 12 is coupled to the spray head body 11.
The nozzle body 11 has a first flow channel 111 therein, one end of the first flow channel 111 is connected to a plurality of extension pipes 112, the extension pipes 112 are disposed at intervals, and an outlet 113 is formed at an end of each extension pipe 112 far away from the first flow channel 111. The plurality of extension pipes 112 may be arranged in parallel, and the outflow ports 113 of the extension pipes 112 are preferably located on the same plane.
The cover 12 is provided with a second flow passage 121, and in the embodiment, the second flow passage 121 is formed between the cover 12 and the nozzle body 11, but not limited thereto. In detail, the cover 12 has a groove therein, so that when the cover 12 is combined with the nozzle body 11, the groove is formed between the cover 12 and the nozzle body 11 to serve as the second flow path 121. One end of the second flow channel 121 is connected to a plurality of sleeves 122, an opening 123 is formed at one end of each sleeve 122 far away from the second flow channel 121, and the openings 123 of each sleeve 122 are arranged at intervals. The plurality of sleeves 122 may be arranged in parallel, and the openings 123 of each sleeve 122 are preferably located on the same plane.
The extension pipes 112 of the nozzle body 11 can pass through the second flow passage 121, and the inner diameter of the sleeve 122 is larger than the outer diameter of the extension pipe 112, so that the extension pipes 112 can respectively extend into the sleeves 122 of the cover body 12, and a space is formed between the outer wall of each extension pipe 112 and the inner wall of the extended sleeve 122. The outflow port 113 of each extension pipe 112 is located between the second flow passage 121 and the opening 123 of each sleeve 122. The extension tubes 112 and the sleeves 122 may be disposed in parallel, so that each extension tube 112 can be aligned with each sleeve 122, and each extension tube 112 can extend into each sleeve 122.
The first flow channel 111 is used for injecting a first fluid F1, so that the first fluid F1 flows along the first flow channel 111 and flows out of the spray head body 11 through the outflow port 113 of each extension pipe 112. The second flow path 121 provides for the injection of a second fluid F2, which flows F2 along the second flow path 121 and out of the housing 12 through the openings 123 of the cannulae 122.
In this embodiment, the second fluid F2 can be prepared by heating the polymer to a glass transition temperature (hereinafter referred to as Tg point temperature) or by adding a small amount of organic solvent (e.g., ethyl acetate, dichloromethane, etc.). The polymer can be biodegradable high molecular material, including aliphatic polyester, aliphatic-aromatic polyester copolymer, polylactic acid-aliphatic polyester copolymer, polycaprolactone, polyglutamic acid, polyhydroxycarboxylate or polylactic acid. In more detail, the aliphatic polyester may be polyglycolic acid, polybutylene succinate or polyethylene succinate. The aliphatic-aromatic polyester copolymer may be polyethylene terephthalate-polyoxyethylene. The polylactic acid-aliphatic polyester copolymer may be polylactic acid polyglycolic acid. However, the invention is not limited thereto, and other biodegradable high molecular materials that can be used as drug microcarriers can be used as the polymer. In this embodiment, the polymer is preferably polycaprolactone, polylactic acid or polylactic acid polyglycolic acid, for example, wherein polycaprolactone has good biocompatibility and miscibility and exhibits excellent permeability for low molecular weight pharmaceutically active ingredients based on a low Tg point temperature and good molecular fluidity in the organism.
Referring to fig. 4, the particle spray head 1 of the embodiment of the present invention can be applied to a particle forming apparatus in practice, and the particle forming apparatus includes a container 2, a fluid intercepting device 3, and a temperature control system 4. The sleeve 122 of the housing 12 extends into the vessel 2. The fluid cut-off device 3 is disposed on the vessel 2, the fluid cut-off device 3 may include a stirring device 31 or an ultrasonic generator 32, or both the stirring device 31 and the ultrasonic generator 32, in this embodiment, the fluid cut-off device 3 has both the stirring device 31 and the ultrasonic generator 32. The stirring device 31 is disposed inside the vessel 2, the ultrasonic generator 32 can be combined with the outer wall of the vessel 2, and the vessel 2 is disposed in the temperature control system 4.
More specifically, the vessel 2 is adapted to be loaded with a third fluid F3, such that the vessel 2 has a liquid level 21, the liquid level 21 being the position of the liquid level when the vessel 2 is loaded with the third fluid F3. The sleeves 122 of the cover 12 extend into the vessel 2 such that the opening 123 of each sleeve 122 is located between the liquid level 21 and a bottom 22 of the vessel 2; in other words, the opening 123 will be located below the liquid level 21, such that the opening 123 is formed in the third fluid F3. The fluid intercepting means 3 is able to cause turbulence in the third fluid F3 loaded in the vessel 2. The stirring device 31 can be driven by a motor to rotate, so as to drive the third fluid F3 to flow. The ultrasonic generator 32 is capable of generating high frequency vibrations, for example, the ultrasonic generator 32 may be composed of a piezoelectric material capable of converting high frequency electric energy into high frequency vibrations and a power source capable of generating high frequency electric energy, and further transmits the high frequency vibrations to the third fluid F3 through the outer wall of the vessel 2, so as to vibrate the third fluid F3. The temperature control system 4 can temperature control the third fluid F3 to maintain the third fluid F3 at a predetermined temperature.
Referring to fig. 4, 5 and 6, the method for forming particles according to an embodiment of the present invention can be performed by using the particle forming apparatus. The particulate forming method of this embodiment includes loading the third fluid F3 with the vessel 2; the temperature control system 4 is activated to maintain the third fluid F3 at a predetermined temperature that is equal to or below the Tg point temperature of the second fluid F2. In this embodiment, the third fluid F3 may be polyvinyl alcohol (PVA) solution with a concentration of 1-15%, but not limited thereto. Extending the sleeve 122 of the enclosure 12 into the containing groove 2, introducing the first fluid F1 into the first flow channel 111 of the nozzle body 11, so that the first fluid F1 flows out of the nozzle body 11 through the outflow ports 113 of the extension pipes 112, and introducing the second fluid F2 into the second flow channel 121 of the enclosure 12, so that the second fluid F2 flows through the second flow channel 121 and the sleeves 122, and further flows out of the enclosure 12 through the openings 123 of the sleeves 122; respectively controlling the pressure of the first flow channel 111 and the second flow channel 121 to make the first fluid F1 capable of flowing at a first flow velocity v1Flows through the extension pipe 112 and enables the second fluid F2 to flow at a second flow velocity v2Through the sleeve 122. By having the second flow velocity v, since the outflow port 113 of each extension pipe 112 is located between the second flow passage 121 and the opening 123 of each sleeve 1222Greater than the first flow velocity v1The first flow velocity v can be used1And the second flow velocity v2The flow velocity difference between them generates a shearing force so that the second fluid F2 can wrap and shear the first fluid F1 flowing out of the outflow port 113, thereby forming a double layer of continuous fluid at the opening 123. The inner layer of the double layer of continuous fluid is the first fluid F1 and the outer layer is the second fluid F2, and the double layer of continuous fluid exits the housing 12 through the openings 123 of each sleeve 122.
Then, the fluid intercepting means 3 is actuated to disturb the third fluid F3 loaded in the vessel 2 to break the double-layered continuous fluid. More specifically, in the present embodiment, the fluid cut-off device 3 has both the stirring device 31 and the ultrasonic generator 32, so that driving the fluid cut-off device 3 may include driving the stirring device 31 to rotate and/or activating the ultrasonic generator 32. The stirring device 31 can drive the third fluid F3 to flow, so as to cut the double-layer continuous fluid flowing out of the cover body 12 by utilizing the shearing force when the third fluid F3 flows, so that the double-layer continuous fluid forms double-layer micro droplets. Alternatively, the ultrasonic generator 32 can vibrate the third fluid F3 to break up the double-layered continuous fluid flowing out of each opening 123, so that the double-layered continuous fluid forms double-layered micro-droplets. The ultrasonic generator 32 can vibrate the third fluid F3 to control the particle size of the formed double-layer micro droplets. At this time, the third fluid F3 loaded in the vessel 2 can cover the outer layer of the double-layer micro droplets (i.e. the "emulsification phenomenon") to assist the solidification and shape of the double-layer micro droplets, so as to form the semi-finished product S shown in fig. 7 in the vessel 2, wherein the semi-finished product S includes the inner layer S1 formed by the first fluid F1, the intermediate layer S2 formed by the second fluid F2, and the outer layer S3 formed by the third fluid F3.
Finally, the semi-finished product S is collected and the outer layer S3 formed by the third fluid F3 is removed, so that a plurality of double-layer finished products M can be formed, wherein the double-layer finished products M only include the inner layer M1 formed by the first fluid F1 and the outer layer M2 formed by the second fluid F2 (as shown in fig. 8). For example, the semi-finished product S is dried (e.g., hot air dried) to evaporate the outer layer S3; alternatively, the intermediate product S may be washed with an aqueous solution to remove the outer layer S3, thereby forming the double-layered final product M. In detail, the operator can collect the semi-finished product S by using the vessel 2; alternatively, referring to fig. 4 and 9, in the present embodiment, the vessel 2 may be provided with an inlet pipe 23 and an outlet pipe 24, the inlet pipe 23 and the outlet pipe 24 penetrate through the outer wall of the vessel 2, and the outlet pipe 24 is preferably disposed adjacent to the bottom surface 22, and the particle forming apparatus may be further provided with a collecting tank 5, and the collecting tank 5 is communicated with the outlet pipe 24 of the vessel 2. Thereby, the third fluid F3 in the vessel 2 flows with the semi-finished products S through the outlet pipe 24 to the collecting tank 5, so that the personnel can collect the semi-finished products S by using the collecting tank 5. On the other hand, the inlet tube 23 is provided for injecting the third fluid F3 to maintain the liquid level 21 of the third fluid F3 in the vessel 2, thereby ensuring that the openings 123 of the respective cannulae 122 are located in the third fluid F3.
The particle spray head 1, the particle forming apparatus and the particle forming method according to the embodiment of the invention can generate the double-layer continuous fluid through the spray head body 11 and the cover body 12 of the particle spray head 1, and can form a large amount of particle semi-finished products S by breaking the double-layer continuous fluid through the shearing force and the vibration of the third fluid F3, thereby producing the double-layer particle finished products M. Therefore, compared to the conventional micro flow channel structure 9 in which the process of forming the particles is long and only a single particle can be formed at a time, the particle spray head 1, the particle forming apparatus and the particle forming method according to the embodiment of the present invention can mass-produce the double-layer particles with uniform particle size, reduce the process time for forming the double-layer particles, and improve the particle production efficiency.
Meanwhile, the particle forming apparatus and the particle forming method according to the embodiments of the present invention can break the double-layer continuous fluid by using the shearing force and/or vibration of the third fluid F3, so that the shearing force of the third fluid F3 is controlled by adjusting the rotation speed of the stirring device 31; and/or by adjusting the frequency and amplitude of the ultrasonic generator 32 to control the vibration of the third fluid F3, the particle size of the formed double-layer particle product M can be precisely controlled. For example, if the viscosity of the first fluid F1 introduced into the first flow channel 111 or the second fluid F2 introduced into the second flow channel 121 is high, the rotation speed of the stirring device 31 or the amplitude of the ultrasonic generator 32 can be increased to ensure that the third fluid F3 can effectively break the double-layer continuous fluid, so as to avoid the influence of the viscosity of the first fluid F1 or the second fluid F2 on the particle size of the formed double-layer particle finished product M, thereby precisely controlling the particle size of the formed double-layer particle finished product M. Therefore, the particle forming device and the particle forming method provided by the embodiment of the invention have the effect of improving the control accuracy of the particle size of the particles.
In addition, as mentioned above, the third fluid F3 may be a stabilizer (such as the aforementioned polyvinyl alcohol (PVA) solution), so that when the double-layer continuous fluid is broken into double-layer micro-droplets, the third fluid F3 can provide a separation effect, thereby preventing the double-layer micro-droplets formed by the first fluid F1 and the second fluid F2 from agglomerating in the third fluid F3. On the other hand, the third fluid F3 is driven to flow by the stirring device 31 and/or the third fluid F3 is driven to vibrate by the ultrasonic generator 32, so that the double-layer micro droplets can be prevented from agglomerating in the third fluid F3. Therefore, the particle forming device and the particle forming method provided by the embodiment of the invention can ensure that the double-layer micro droplets are coated and shaped by the third fluid F3, and have the effect of improving the production yield of particles.
Based on the above technical concept, the characteristics of the particle spray head 1, the particle forming apparatus and the particle forming method according to the embodiment of the present invention are described below in detail:
referring to fig. 6, it should be noted that, in order to make the second fluid F2 completely cover the first fluid F1 flowing out from the outflow port 113 at the opening 123, a space is preferably kept between the opening 123 of each sleeve 122 and the outflow port 113 of each extension pipe 112, so that each sleeve 122 can form a forming space 124 between the opening 123 and the outflow port 113. The size of the forming space 124 can be adjusted according to the difference between the surface tensions of the first fluid F1 and the second fluid F2, so as to ensure that the second fluid F2 completely covers the first fluid F1 flowing out from the outflow port 113 at the opening 123.
As described above, the particle forming method of the embodiment of the invention can control the pressures of the first fluid F1 and the second fluid F2 respectively, so that the first fluid F1 and the second fluid F2 respectively have the first flow velocity v1And the second flow velocity v2Through the extension tube 112 and the sleeve 122, a double layer of continuous fluid is formed and driven into the third fluid F3 through the openings 123 of the housing 12. Therefore, please refer to FIG. 4In the embodiment shown, the cover 12 extends into the vessel 2 of the particle forming apparatus from a horizontally upper position of the vessel 2; alternatively, referring to fig. 10, in some embodiments of the present invention, the cover 12 also extends into the vessel 2 from a horizontal lower position of the vessel 2; the same process is carried out; in other embodiments of the present invention, the cover 12 may also extend into the vessel 2 from a position horizontal to the vessel 2. In other words, the present invention does not limit the relative position between the cover 12 and the vessel 2, and the double-layer continuous fluid can be driven into the third fluid F3 by only extending the sleeves 122 of the cover 12 into the vessel 2 and positioning the openings 123 of the sleeves 122 below the liquid level 21.
Meanwhile, referring to fig. 4, in the present embodiment, the temperature control system 4 may be a heating coil, and the temperature control system 4 is combined with the outer wall of the vessel 2. Thereby, the temperature control system 4 can heat the third fluid F3 through the outer wall of the vessel 2 to maintain the third fluid F3 at the predetermined temperature. Alternatively, as shown in FIG. 10, in some embodiments of the present invention, the temperature control system 4 may be an oven, and the vessel 2 may be disposed inside the temperature control system 4. Thereby, the temperature control system 4 is also able to maintain the third fluid F3 at the predetermined temperature.
In the particle forming method according to the embodiment of the invention, the temperature control system 4 is activated to maintain the third fluid F3 at the predetermined temperature, so that when the second fluid F2 forms micro droplets, the temperature of the third fluid F3 can assist the micro droplets to solidify and shape. However, as mentioned above, the second fluid F2 can be made by adding a small amount of organic solvent to the polymer, so that in some cases, the solidification and setting of the microdroplets formed by the second fluid F2 is not clearly related to the temperature of the third fluid F3, and therefore, in the method for forming microparticles according to some embodiments of the present invention, the temperature control system 4 may not be activated.
In addition, the first fluid F1 may be a liquid with a medicinal composition, such as: nitrosourea mustard (1,3-bis (2-chloroethyl) -1-nitrourea, BCNU), Doxorubicin (Doxorubicin, DOX). Therefore, when the double-layer particle product M composed of the first fluid F1 and the second fluid F2 is administered to a living body, the second fluid F2 can coat the double-layer particle product M to realize the effect of slowly releasing the medicinal component. On the other hand, in some embodiments of the present invention, a gas may be used as the first fluid F1 to form a double-layered particle product M 'as shown in fig. 11, which will include the gaseous inner layer M1' formed by the first fluid F1.
In some embodiments, the end of each sleeve 122 having the opening 123 may be provided with a layer of hydrophobic material. The hydrophobic material may be SiO2Or TiO2However, the present invention is not limited thereto. The layer of hydrophobic material can be formed at the end of each sleeve 122 having the opening 123 by (but not limited to) plating, and by disposing the layer of hydrophobic material at the opening 123 of each sleeve 122, the double-layer continuous fluid can contact the layer of hydrophobic material when flowing out through each opening 123, so that the double-layer continuous fluid is not easily attached to each sleeve 122, thereby preventing the double-layer continuous fluid from accumulating at each opening 123 to reduce the influence of surface tension on the particle size of the formed double-layer particle finished product M.
In summary, the particle spray head 1, the particle forming apparatus and the particle forming method according to the embodiments of the invention generate the double-layer continuous fluid through the spray head body 11 and the cover body 12 of the particle spray head 1, and break the double-layer continuous fluid by using the shearing force and/or the vibration of the third fluid F3, so as to form a large amount of the particle semi-finished product S, thereby mass-producing the double-layer particles with uniform particle size, reducing the process time for forming the double-layer particles, and improving the particle production efficiency.
Meanwhile, the particle forming apparatus and the particle forming method according to the embodiments of the present invention can break the double-layer continuous fluid by using the shearing force and/or vibration of the third fluid F3, so that the shearing force of the third fluid F3 is controlled by adjusting the rotation speed of the stirring device 31; or the frequency and amplitude of the ultrasonic generator 32 are adjusted to control the vibration of the third fluid F3, so as to precisely control the particle size of the formed double-layer particle product M, and the method is suitable for the case that the viscosity of the second fluid F2 is high, and has the effect of improving the control precision of the particle size.
In addition, the second fluid F2 can provide an isolation effect to prevent the double-layer micro droplets formed by the first fluid F1 and the second fluid F2 from agglomerating in the third fluid F3, and the particle forming apparatus and the particle forming method can drive the third fluid F3 to flow through the stirring device 31 and/or drive the third fluid F3 to vibrate through the ultrasonic generator 32, and can also prevent the double-layer micro droplets from agglomerating in the third fluid F3, thereby ensuring that the double-layer micro droplets are all coated and shaped by the third fluid F3, and improving the yield of the particles.
Although the present invention has been disclosed with reference to the above preferred embodiments, it should be understood that the present invention is not limited thereto, and those skilled in the art can make various changes and modifications to the above embodiments without departing from the technical spirit and scope of the present invention.

Claims (17)

1. A particle forming apparatus for mass-producing double-layered particles, the particle forming apparatus being provided with a particle spray head comprising:
the spray head comprises a spray head body, a first flow channel is arranged in the spray head body, one end of the first flow channel is connected with a plurality of extension pipes, the extension pipes are arranged at intervals, and one end of each extension pipe, which is far away from the first flow channel, forms an outflow port; and
the cover body is provided with a second flow passage, one end of the second flow passage is connected with a plurality of sleeves, one end of each sleeve, which is far away from the second flow passage, forms an opening, and one end of each sleeve, which is provided with the opening, is provided with a layer of hydrophobic material;
wherein the plurality of extension pipes respectively extend into the sleeves, a space is arranged between the outer wall of each extension pipe and the inner wall of the extended sleeve, the outflow port of each extension pipe is positioned between the second flow passage and the opening of each sleeve,
the particle forming apparatus, and further comprising: the extension pipe of the spray head body extends into the containing groove;
the fluid cut-off device is arranged on the containing groove and can drive the fluid loaded in the containing groove to generate disturbance; and
and the accommodating groove is arranged in the temperature control system.
2. The particulate forming apparatus according to claim 1, wherein: the plurality of extension pipes are arranged in parallel with the plurality of sleeves.
3. The particulate forming apparatus according to claim 1, wherein: the second flow passage is formed between the cover body and the spray head body, and a plurality of extension pipes of the spray head body penetrate through the second flow passage.
4. The particulate forming apparatus according to claim 1, wherein: each sleeve forms a forming space between the opening and the outflow opening of each extension pipe.
5. The particulate forming apparatus according to claim 1, wherein: the containing groove is used for containing a third fluid, the liquid level of the third fluid is a liquid level height, and the opening of each sleeve is positioned below the liquid level height.
6. The particulate forming apparatus according to claim 1, wherein: the collecting tank is also arranged, the containing tank is provided with an inlet pipe and an outlet pipe, the inlet pipe and the outlet pipe penetrate through the outer wall of the containing tank, and the collecting tank is communicated with the outlet pipe of the containing tank.
7. The particulate forming apparatus according to claim 1, wherein: the fluid cut-off device comprises a stirring device arranged in the containing groove.
8. The particulate forming apparatus according to claim 1, wherein: the fluid cut-off device comprises an ultrasonic generator combined with the outer wall of the containing groove.
9. A method of forming fine particles, comprising: performed with the particle molding apparatus as claimed in claim 1, the particle molding method comprising:
loading a third fluid into the vessel such that the openings of the sleeves are located in the third fluid;
introducing a first fluid into a first flow channel of the spray head body, enabling the first fluid to flow through the extension pipe at a first flow rate, introducing a second fluid into the sleeve of the cover body, enabling the second fluid to flow through the sleeve at a second flow rate, wherein the second flow rate is greater than the first flow rate, and enabling the second fluid to coat and shear the first fluid flowing out of the outflow port of the extension pipe so as to form a double-layer continuous fluid flowing out through the openings of the sleeves;
driving the fluid cut-off device to make the third fluid generate disturbance, so that the double-layer continuous fluid forms a particle semi-finished product in the vessel;
collecting the particulate intermediates, the particulate intermediates including an inner layer formed by the first fluid, an intermediate layer formed by the second fluid, and an outer layer formed by the third fluid; and
removing the outer layer of the semi-finished product of the particles and forming a double-layer particle finished product.
10. The method of forming fine particles according to claim 9, wherein: the second fluid is prepared by heating the biodegradable polymer material to a glass transition temperature.
11. The method of forming fine particles according to claim 10, wherein: before passing the second fluid into the second channel, the temperature control system is activated to maintain the third fluid at a predetermined temperature that is equal to or lower than the glass transition temperature of the second fluid.
12. The method of forming fine particles according to claim 9, wherein: the second fluid is prepared by adding biodegradable high molecular materials into an organic solvent.
13. The method of forming fine particles according to claim 9, wherein: the first fluid is a liquid having a pharmaceutical composition.
14. The method of forming fine particles according to claim 9, wherein: the first fluid is a gas.
15. The method of forming fine particles according to claim 9, wherein: the third fluid is a stabilizer.
16. The method of forming fine particles according to claim 15, wherein: the stabilizer is polyvinyl alcohol solution with concentration of 1-15%.
17. The method of forming fine particles according to claim 9, wherein: and (3) treating the plurality of particle semi-finished products by a drying method, or washing the particle semi-finished products by using an aqueous solution to remove the outer layer.
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Publication number Priority date Publication date Assignee Title
CN1314146A (en) * 2001-02-12 2001-09-26 孙传经 Supercritical CO2 solvent-resistant device for producing nanometer material
CN1395987A (en) * 2001-07-13 2003-02-12 中国科学院大连化学物理研究所 System for preparing gel beads
CN101693177A (en) * 2009-10-19 2010-04-14 上海现代药物制剂工程研究中心有限公司 Ultrasonic technology-based method for preparing microsphere and device thereof
CN105754116A (en) * 2016-05-11 2016-07-13 中国工程物理研究院激光聚变研究中心 Detachable no-adhesive type emulsion granule generator

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1314146A (en) * 2001-02-12 2001-09-26 孙传经 Supercritical CO2 solvent-resistant device for producing nanometer material
CN1395987A (en) * 2001-07-13 2003-02-12 中国科学院大连化学物理研究所 System for preparing gel beads
CN101693177A (en) * 2009-10-19 2010-04-14 上海现代药物制剂工程研究中心有限公司 Ultrasonic technology-based method for preparing microsphere and device thereof
CN105754116A (en) * 2016-05-11 2016-07-13 中国工程物理研究院激光聚变研究中心 Detachable no-adhesive type emulsion granule generator

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