CN113559799B - High-efficiency injection method and device for medical degradable high polymer material microspheres - Google Patents
High-efficiency injection method and device for medical degradable high polymer material microspheres Download PDFInfo
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- CN113559799B CN113559799B CN202110877942.8A CN202110877942A CN113559799B CN 113559799 B CN113559799 B CN 113559799B CN 202110877942 A CN202110877942 A CN 202110877942A CN 113559799 B CN113559799 B CN 113559799B
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- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/04—Making microcapsules or microballoons by physical processes, e.g. drying, spraying
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- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
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Abstract
A high-efficiency spraying method and a device for medical degradable high polymer material microspheres comprise an array type multi-nozzle, wherein an annular electrode is arranged below the array type multi-nozzle, and a collector is arranged below the annular electrode; the array type multi-nozzle, the annular electrode and the collector are connected with the high-voltage electrostatic generator; a flat nozzle spray head is arranged at an outlet below the collector, a stainless steel filter mesh belt is attached to the lower part of the flat nozzle spray head, a collected liquid recovery hopper is arranged below the filter mesh belt, an outlet of the collected liquid recovery hopper is connected with an inlet of a gravity settling tank, an outlet of the gravity settling tank is connected with a flushing nozzle through a reflux pump, and the flushing nozzle is arranged at the edge of the collector; the stainless steel filter mesh belt penetrates through the heating cavity, the powder scraping roller is matched with the stainless steel filter mesh belt, the powder scraping roller is tightly attached to an inlet of the collecting guide pipe, an outlet of the collecting guide pipe is connected with an inlet of the cyclone separator, a smoke outlet of the cyclone separator is connected with a draught fan, and a discharge port of the cyclone separator is connected with the powder collecting tank; the invention realizes the high-efficiency preparation, separation, drying and collection of the medical degradable high polymer material microspheres.
Description
Technical Field
The invention relates to the technical field of biological manufacturing and electrostatic spraying, in particular to a method and a device for efficiently spraying medical degradable high polymer material microspheres.
Background
The degradable high molecular material microspheres are spheres made of biodegradable or resorbable high molecular polymers, and the diameters of the spheres are usually in the micrometer or nanometer range. The degradable high molecular material microspheres can coat micromolecular drugs, bioactive macromolecules (such as protein, enzyme and DNA) and even living cells and the like, and have wide application value in the fields of drug delivery, genetic engineering, tissue engineering and the like.
The current preparation methods of the degradable high polymer material microspheres include an emulsification method, a spray drying method, a microfluidic method, a heating dispersion method and an electrostatic spraying method; among them, the electrostatic spraying method has the advantages of simple process, good material universality, high purity of the prepared microspheres and the like, and is widely used for manufacturing pure powder microspheres and core-shell structure microspheres. However, the yield of the microspheres prepared by the existing single-nozzle electrostatic spraying in the market is low, and the requirement of large-scale application is difficult to meet.
The prior electrostatic spraying system based on multiple spray heads has the following defects:
the problem that the arrangement density of the spray heads is maximized is not systematically researched in the conventional multi-spray-head arrangement scheme, and the limitation of low space utilization rate exists;
the existing multi-nozzle arrangement scheme adopts modes such as linear arrangement, rectangular array, hexagonal array and the like, the electric field intensity of a central nozzle is low, the electric field intensity of peripheral nozzles is high, and the problem that the injection states of the inner nozzle and the outer nozzle are different due to large difference of the electric field intensities of the inner nozzle and the outer nozzle, so that the shape and size deviation of microspheres is large is caused;
the existing multi-nozzle electrostatic spraying mostly adopts an injection pump and a multi-branch flow channel to supply liquid, and the manufacturing and assembling errors easily cause uneven flow velocity among all nozzles, so that the prepared microspheres have large shape and size differences;
at present, an automatic separation and collection device aiming at electrostatic spraying microspheres is lacked in the market, and the risk of introducing impurities and pollution is increased by manual collection.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide a method and a device for efficiently spraying medical degradable high polymer material microspheres, which solve the problems of large electric field intensity difference of needle points in different areas when an array needle is subjected to high pressure application and large spraying liquid drop range and difficulty in collection, can realize efficient preparation of the medical degradable high polymer material microspheres, can also realize automatic separation, drying and collection of the microspheres, and greatly expand the application capability of the technology.
In order to achieve the purpose, the invention adopts the technical scheme that:
a medical degradable high polymer material microsphere high-efficiency injection device comprises a working platform 1, wherein a pair of dustproof motors 4 are arranged in the working platform 1, and an array type multi-nozzle 2 is arranged on a sliding table 3 of each dustproof motor 4; an annular electrode 6 is arranged under the array type multi-nozzle 2, and the annular electrode 6 is fixed on the working platform 1 through an annular electrode bracket 5 and an annular electrode lifting guide rail 29; a collector 9 is arranged right below the annular electrode 6; the array type multi-nozzle 2, the annular electrode 6 and the collector 9 are respectively connected with a first channel, a second channel and a grounding end of the high-voltage electrostatic generator 26; an electromagnetic straight-through valve 10 and a flat nozzle spray head 11 are arranged at an outlet below the collector 9, a stainless steel filter mesh belt 12 is attached below the flat nozzle spray head 11, and the stainless steel filter mesh belt 12 is driven by a stepping motor 17; a collected liquid recovery hopper 14 is arranged below the stainless steel filter mesh belt 12, the outlet of the collected liquid recovery hopper 14 is connected with the inlet of the gravity settling tank 13, the outlet of the gravity settling tank 13 is connected with the inlet of a reflux pump 16, the outlet of the reflux pump 16 is connected with a scouring spray head 7, and the scouring spray head 7 is arranged at the edge of the collector 9;
a heating cavity 15 is arranged on one side of a flat nozzle spray head 11, a stainless steel filter mesh belt 12 penetrates through the heating cavity 15, one end of the heating cavity 15 is tightly attached to a powder scraping roller 20, the powder scraping roller 20 is matched with the stainless steel filter mesh belt 12, the powder scraping roller 20 is tightly attached to an inlet of a collecting guide pipe 21, an outlet of the collecting guide pipe 21 is connected with an inlet of a cyclone separator 25, the cyclone separator 25 is fixed in a working platform 1 through a separator bracket 23, a smoke exhaust port of the cyclone separator 25 is connected with a draught fan, a discharge port of the cyclone separator 25 is connected with a powder collecting tank 22, and the powder collecting tank 22 is placed in the working platform 1; the powder brushing roller 20 is connected with the driving motor 18;
an FFU fan filter unit 30 and an air outlet efficient filter 24 are installed on a shell of the working platform 1, and the FFU fan filter unit 30, the dustproof motor 4, the high-voltage electrostatic generator 26, the air pressure controller 27, the stepping motor 17 and the reflux pump 16 are all connected with an industrial personal computer.
The array type multi-nozzle 2 comprises a needle cylinder 201, the needle cylinder 201 is arranged on a needle cylinder retainer 202, and two sides below the needle cylinder retainer 202 are fixed on the working platform 1 through a multi-nozzle bracket 203; the lower part of the syringe 201 is connected with a syringe bracket 204 capable of adjusting the height difference of the syringes among layers, the syringe bracket 204 is connected with the syringe retainer 202 through a bearing bolt 206, and a limit sleeve 207 is sleeved outside the bearing bolt 206; the bottom of the syringe 201 is connected with a stainless steel nozzle 205.
The stainless steel nozzles 205 are arranged in a concentric circumferential array layer-by-layer manner and are symmetrical along the connecting line from the central stainless steel nozzle 205 to any stainless steel nozzle 205; the arrangement number of the stainless steel nozzles 205 in each layer is obtained according to the principle of maximizing the density of the stainless steel nozzles 205.
The syringe bracket 204 capable of adjusting the height difference of the syringes between the layers comprises a plurality of layers of syringe supporting plates and adjusting bolts for adjusting the height difference between the syringe supporting plates of the adjacent layers; the distance between the needle point of the stainless steel spray nozzle 205 in the array type multi-spray nozzle 2 and the receiver is adjusted to 10-50cm, and the adjusting bolts of all layers are adjusted to keep the electric field intensity at the needle point of the stainless steel spray nozzle 205 of each layer under the same high pressure so as to achieve the effect of the stainless steel spray nozzles 205 of all layers in a coordinated and stable spraying manner.
The adjustable range of the annular electrode 6 relative to the collector 9 is 0-50cm, any one or more materials of a copper electrode, an aluminum electrode, a steel electrode and a composite conductive material are selected, the inner diameter range of the annular electrode changes along with the size of the outermost layer of the array type multi-nozzle 2, and the upper connection voltage changes along with the spraying voltage of the array type multi-nozzle 2 so as to restrict the spreading range of microspheres sprayed by the array type multi-nozzle 2.
The array type multi-nozzle 2 is supplied by a precise injection pump, a resorption type electric screw device, a charging barrel containing a precise extrusion device or an air pressure liquid supply device adopting an air pump-air pressure controller-air distribution and discharge-charging barrel.
The whole appearance of collector 9 be hopper-shaped, contain the collecting fluid and be used for buffering the microballon that high-speed flies to penetrate and down, the opening diameter of collector 9 upper end changes along with microballon dispersion scope, the opening of collector 9 lower extreme is the pipe screw interface of standard, the collecting fluid can wrap up in when electromagnetism straight-through valve 10 opens and hold the microballon and flow out from the lower extreme opening automatically.
The heating cavity 15 is made of aluminum alloy, the temperature of the heating cavity 15 is controlled by a temperature control heater to be kept constant, and the temperature adjusting range is 25-210 ℃.
The high-voltage electrostatic generator 26 can adjust the voltage amplitude to be 0-50 KV.
The method for utilizing the medical degradable high polymer material microsphere high-efficiency spraying method and the device comprises the following steps:
1) a degradable polymer solution configured for electrostatic spraying;
2) the degradable polymer solution is subpackaged into each needle cylinder 201 of the array type multi-nozzle 2;
3) the FFU fan filter unit 30 is operated, the dustproof stepping motor 4 is operated, the height between the array type multi-nozzle 2 and the collector 9 is adjusted, the height between the annular electrode 6 and the collector 9 is adjusted, the voltage applied to the array type multi-nozzle 2 and the voltage applied to the annular electrode 6 are adjusted according to requirements, and the coordinated stable spraying of the stainless steel nozzle 205 and the controllable deposition of microspheres are realized;
4) running a control program, controlling the electromagnetic two-way valve 10 to send the degradable polymer microspheres in the collector 9 to a stainless steel filter screen 12 below through a flat nozzle spray head 11, filtering the collected liquid, flowing through a collected liquid recovery hopper 14, and entering a gravity settling tank 13 to realize automatic separation of the degradable polymer microspheres and the collected liquid; controlling the reflux pump 16 to pressurize and convey the collection liquid to the position of the scouring spray head 7 by the reflux pump 16 to scour the bottom of the collector 9 so as to prevent the degradable polymer microspheres from being adhered to each other; controlling a stepping motor 17 to enable a stainless steel filter screen 12 to drive the degradable polymer microspheres to pass through a heating cavity 15 at a constant speed, evaporating residual collecting liquid on the surfaces of the degradable polymer microspheres, and realizing automatic drying of the degradable polymer microspheres; the powder brushing roller 20 is controlled to brush down the completely dried degradable polymer microspheres on the stainless steel filter screen 12, and the degradable polymer microspheres are collected into the powder collecting tank 22 through the cyclone separator 25, so that the automatic collection of the degradable polymer microspheres is realized.
The degradable polymer solution is a hydrogel precursor solution, or the polyester polymer is dissolved in an organic solvent which is easy to evaporate and has no residue, and the concentration range of the solution is adjustable between 0.5 and 20w/v percent; the hydraulic precursor is polyvinyl alcohol copolymer, collagen, gelatin, sodium alginate or photocuring hydrogel; the polyester polymer is polycaprolactone, polylactic acid, polypropylene or polylactic acid-glycolic acid copolymer, and the organic solvent is acetic acid, dichloromethane or hexafluoroisopropanol.
Determining a curing mode of the degradable polymer microspheres according to the properties of the degradable polymer material; when the degradable polymer solution is a hydrogel precursor solution, according to different crosslinking methods, curing the hydrogel precursor solution by controlling the temperature of a working space or adding ions for initiating crosslinking into a collection liquid or by adding a photoinitiator and installing a photocuring module to obtain hydrogel precursor microspheres; when the degradable polymer solution is polyester polymer solution, the evaporation of the solvent is accelerated by blowing fresh air or applying negative pressure or raising the temperature, and the solid polyester polymer microspheres are obtained.
When the degradable polymer microspheres are hydrogel precursor microspheres, a control program is operated to control the opening or the periodic on-off of the electromagnetic two-way valve 10, and the collected liquid and the hydrogel precursor microspheres in the collector 9 are directly conveyed into the gravity settling tank 13 by utilizing the actions of gravity, vibration, pumping or flushing and the collected liquid conveying to realize the automatic collection of the hydrogel precursor microspheres.
When the degradable polymer microspheres are polyester polymer microspheres, a control program is operated to control the opening or the periodic on-off of the electromagnetic two-way valve 10, the collected liquid and the polyester polymer microspheres in the collector 9 are conveyed to a stainless steel filter screen 12 below by utilizing the actions of gravity, vibration, pumping or flushing and the collected liquid conveying, the collected liquid enters a gravity settling tank 13 after being filtered, and the polyester polymer microspheres are retained on the stainless steel filter screen 12 to realize the automatic separation of the polyester polymer microspheres and the collected liquid; controlling the reflux pump 16 to work periodically, pressurizing and conveying the collected liquid by the reflux pump 16 to reflux into the collector 9, and flushing the bottom of the collector 9 by the collected liquid to prevent the polyester polymer microspheres from being adhered to each other; controlling a stepping motor 17 to drive a stainless steel filter screen 12 to rotate at a constant speed, driving polyester polymer microspheres to pass through a heating cavity 15 at a constant speed, and thoroughly removing residual collecting liquid on the surfaces of the polyester polymer microspheres to realize automatic drying of the degradable polymer microspheres; the driving motor 18 of the powder brushing roller is controlled to rotate at a constant speed, polyester polymer microspheres which are completely dried on the stainless steel filter screen 12 are brushed down, and the degradable polymer microspheres are collected into the powder collecting tank 22 through the cyclone separator 25, so that the automatic collection of the polyester polymer microspheres is realized.
Compared with the prior art, the invention has the beneficial effects that:
1) the device maximizes the density of the stainless steel spray heads 205, and maximizes the arrangement efficiency of multiple spray heads.
2) The device array type multi-nozzle adopts the needle cylinder bracket 204 capable of adjusting the height difference of the needle cylinders among the layers to replace the traditional multi-nozzle arrangement with single height, and the electric field intensity at the needle points of the plurality of stainless steel nozzles 205 is basically consistent under the same voltage.
3) The invention adopts air pressure liquid supply to replace the traditional injection pump liquid supply, effectively controls the flow rate of each stainless steel spray nozzle 205 to be basically consistent, and realizes the simultaneous synergic stable spraying of a plurality of stainless steel spray nozzles 205.
4) The device realizes the automatic separation, drying and collection of the degradable polymer microspheres, and simultaneously ensures that the whole process of preparation, separation, drying and collection of the medical degradable polymer microspheres is in a clean environment; has very important significance for large-scale application of medical degradable polymer microspheres in the fields of biological manufacture and biological medical treatment.
Drawings
FIG. 1 is a schematic view of the structure of the apparatus of the present invention.
FIG. 2 is a bottom view of an array type multiple nozzles according to an embodiment of the present invention.
Fig. 3 is a front view of an array type multi-nozzle of an embodiment of the present invention.
FIG. 4 is a schematic view of an array type syringe carrier according to an embodiment of the present invention.
FIG. 5 is a comparison of the electric field strength finite element analysis results of the arrayed multi-nozzle of the embodiment of the present invention and the conventional arrayed multi-nozzle.
FIG. 6 shows the finite element analysis result of the electric field binding of the degradable polymer microspheres by using the annular electrode in the embodiment of the invention.
FIG. 7 is a microscopic image of degradable polymeric microspheres prepared by an example of the present invention.
Detailed Description
The following detailed description of the present invention, taken in conjunction with the examples and the accompanying drawings, is intended to illustrate and provide further explanation of the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise. The features of the present embodiment and embodiments may be combined with each other without conflict.
As shown in fig. 1, a medical degradable high polymer material microsphere high-efficiency injection device comprises a working platform 1, wherein a pair of dustproof motors 4 are arranged in the working platform 1, an array type multi-nozzle 2 is arranged on a sliding table 3 of the dustproof motors 4, and the array type multi-nozzle 2 can move up and down by depending on the dustproof motors 4; the array type multi-nozzle 2 is sequentially connected with the gas distribution row 28 and the air pressure controller 27 through gas pipes, and the gas distribution row 28 and the air pressure controller 27 are fixed on the working platform 1; an annular electrode 6 is arranged under the array type multi-nozzle 2, the annular electrode 6 is arranged on an annular electrode lifting guide rail 29 through an annular electrode bracket 5, the annular electrode lifting guide rail 29 is fixed on the working platform 1, and the height of the annular electrode 6 can be adjusted up and down; a collector 9 is arranged right below the annular electrode 6, and the collector 9 is fixed in the working platform 1; the array type multi-nozzle 2, the annular electrode 6 and the collector 9 are respectively connected with a first channel, a second channel and a grounding end of the high-voltage electrostatic generator 26; an electromagnetic straight-through valve 10 and a flat nozzle spray head 11 are arranged at an outlet below the collector 9, a stainless steel filter mesh belt 12 is attached below the flat nozzle spray head 11, the stainless steel filter mesh belt 12 synchronously moves along with a synchronous belt on a belt pulley, and the belt pulley is connected with a stepping motor 17; a collected liquid recovery hopper 14 is arranged below the stainless steel filter mesh belt 12, the outlet of the collected liquid recovery hopper 14 is connected with the inlet of the gravity settling tank 13, the outlet of the gravity settling tank 13 is connected with the inlet of a reflux pump 16, the outlet of the reflux pump 16 is connected with a scouring spray head 7, and the scouring spray head 7 is arranged at the edge of the collector 9;
a heating cavity 15 is arranged on the left side of a flat nozzle spray head 11, a stainless steel filter mesh belt 12 penetrates through the heating cavity 15, the left end of the heating cavity 15 is tightly attached to a powder wiping roller 20, the powder wiping roller 20 is fixed on a working platform 1 through a filter screen mounting plate 19, the powder wiping roller 20 is matched with the stainless steel filter mesh belt 12, the left side of the powder wiping roller 20 is tightly attached to an inlet of a collecting guide pipe 21, an outlet of the collecting guide pipe 21 is connected with an inlet of a cyclone separator 25, the cyclone separator 25 is fixed in the working platform 1 through a separator bracket 23, a smoke outlet of the cyclone separator 25 is connected with a draught fan, a discharge port of the cyclone separator 25 is connected with a powder collecting tank 22, and the powder collecting tank 22 is placed in the working platform 1; the powder brushing roller 20 is connected with the driving motor 18;
an FFU fan filter unit 30 and an air outlet efficient filter 24 are installed on a shell of the working platform 1, and the FFU fan filter unit 30, the dustproof motor 4, the high-voltage electrostatic generator 26, the air pressure controller 27, the stepping motor 17 and the reflux pump 16 are all connected with an industrial personal computer.
Referring to fig. 2 and 3, the array type multi-nozzle 2 comprises a needle cylinder 201, the needle cylinder 201 is mounted on a needle cylinder holder 202, and two sides below the needle cylinder holder 202 are fixed on a working platform 1 through an insulating gasket 208 and a multi-nozzle bracket 203; the lower part of the syringe 201 is connected with a syringe bracket 204 capable of adjusting the height difference of the syringes among layers, the syringe bracket 204 is connected with the syringe retainer 202 through a bearing bolt 206, and a limit sleeve 207 is sleeved outside the bearing bolt 206; the bottom of the needle cylinder 201 is connected with a stainless steel spray head 205;
the stainless steel nozzles 205 are arranged in a concentric circumferential array hierarchy, and are symmetrical along the connecting line from the central stainless steel nozzle 205 to any stainless steel nozzle 205; in this embodiment, the size of the stainless steel showerhead 205 is 32mm, and the minimum distance L between any stainless steel showerhead 205 and the adjacent stainless steel showerhead 205 is greater than 32mm, i.e. min { L1, L2, L3} is greater than or equal to 32, the arrangement number of the stainless steel showerheads 205 in each layer is 1-6-12-12-24 (taking five layers as an example) according to the maximization principle of the density of the stainless steel showerhead 205 (the number of the stainless steel showerheads 205 in a unit area: number/mm 2), and the distribution diameter of the outermost circle of the stainless steel showerhead 205 is 245 mm.
Referring to fig. 4, the syringe bracket 204 (five layers as an example) capable of adjusting the inter-layer syringe height difference includes a first-layer syringe support plate 204-1, a second-layer syringe support plate 204-2, a third-layer syringe support plate 204-3, a fourth-layer syringe support plate 204-4, and a fifth-layer syringe support plate 204-5, and a first adjusting bolt 204-6 for adjusting the height difference between the four-layer syringe supporting plate 204-4 and the five-layer syringe supporting plate 204-5, a second adjusting bolt 204-7 for adjusting the height difference between the three-layer syringe supporting plate 204-3 and the four-layer syringe supporting plate 204-4, a third adjusting bolt 204-8 for adjusting the height difference between the two-layer syringe supporting plate 204-2 and the three-layer syringe supporting plate 204-3, a fourth adjusting bolt 204-9 for adjusting the height difference between the first-layer syringe supporting plate 204-1 and the second-layer syringe supporting plate 204-2; the distance between the needle point of the lowest stainless steel nozzle 205 in the array type multi-nozzle 2 and the receiver is adjusted to 20cm, and the adjusting bolts of each layer are adjusted to keep the electric field intensity at the needle point of each layer of stainless steel nozzle 205 under the same high pressure basically consistent (as shown in fig. 5), so that the effect of the coordinated and stable spraying of each layer of stainless steel nozzle 205 is achieved, and the traditional nozzle arrangement mode with the same height shows the problem that the peripheral electric field intensity is obviously larger than the inner layer electric field intensity.
As shown in fig. 6, the annular electrode 6 is located right below the array type multi-nozzle 2, the height of the annular electrode relative to the collector 9 is adjusted to 20cm, the inner diameter of the annular electrode 6 is 30cm, and any one or more materials of a copper electrode, an aluminum electrode, a steel electrode and a composite conductive material are selected; the upper voltage was applied with a multi-nozzle spray jet of 27kv and the presence of the ring electrode 6 spreads the powder from 1.07E 5mm compared to no ring electrode 62Significantly reduced to 8.5E4 mm2So as to restrict the spreading range of the microspheres ejected by the array type multi-nozzle 2 and reduce the waste of raw materials.
The array type multi-nozzle 2 is supplied by a precise injection pump, a resorption type electric screw device and a material cylinder containing a precise extrusion device or an air pressure liquid supply device of an air pump-air pressure controller-air distribution and discharge-material cylinder, and the air pressure liquid supply device is preferably selected to avoid the difficult problem of uneven liquid distribution of the injection pump, so that the uniform liquid injection amount is realized.
The collector 9 is positioned right below the array type multi-nozzle 2 and the annular electrode 6, the whole appearance is funnel-shaped, a certain amount of collecting liquid is filled in the collector to buffer microspheres flying at a high speed, the diameter of an opening at the upper end of the collector 9 changes along with the spreading range of the microspheres, the opening at the lower end of the collector 9 is a standard 1/2-inch threaded pipe connector, the inner diameter of a pipe opening is 18mm, the taper of the collector 9 is 10:1, and the collecting liquid can wrap the microspheres when the electromagnetic straight-through valve 10 is opened and automatically flows out from the opening at the lower end.
The high-voltage electrostatic generator 26 can adjust the voltage amplitude to be 0-50 KV.
The method for utilizing the medical degradable high polymer material microsphere high-efficiency injection device comprises the following steps of forming Taylor cone injection at an array type multi-nozzle by using a degradable polymer solution driven by high-voltage static, and crushing charged liquid drops obtained by injection into smaller charged micro-droplets by using the electrostatic repulsion force greater than the surface tension, wherein the charged micro-droplets comprise the following components in parts by weight:
1) preparing a degradable polymer solution, wherein the degradable polymer solution is a degradable polycaprolactone solution with the concentration of 8 w/v%, and a solvent is dichloromethane;
2) the degradable polymer solution is subpackaged into each needle cylinder 201 of the array type multi-nozzle 2;
3) the FFU fan filter unit 30 is operated, the dustproof stepping motor 4 is operated, the height between the array type multi-nozzle 2 and the collector 9 is adjusted to be 20cm, the height between the annular electrode 6 and the collector 9 is adjusted to be 20cm, the voltage applied to the array type multi-nozzle 2 is adjusted to be 40KV according to requirements, the voltage applied to the annular electrode 6 is adjusted to be 28KV, and the purposes of realizing the cooperative stable injection of 55 stainless steel nozzles 205 and the controllable deposition of degradable polymer microspheres are achieved;
4) running a control program, controlling the electromagnetic two-way valve 10 to be opened every 15 seconds for 15 seconds, conveying the degradable polymer microspheres in the collector 9 to a stainless steel filter screen 12 below through a flat nozzle spray head 11 by utilizing the gravity and the carrying effect of the collected liquid, filtering the collected liquid, and then flowing through a collected liquid recovery hopper 14 to enter a gravity settling tank 13, so as to realize the automatic separation of the degradable polymer microspheres and the collected liquid; controlling the reflux pump 16 to work for 5 seconds every 25 seconds, pressurizing and conveying the collected liquid to the position of the flushing nozzle 7 by the reflux pump 16, flushing the bottom of the collector 9 by the high-pressure collected liquid, and preventing the degradable polymer microspheres from being adhered to each other; controlling a stepping motor 17 of a driving belt pulley to rotate at a constant speed of 10r/min, synchronously moving a stainless steel filter screen 12 along with a stepping belt to drive the degradable polymer microspheres to pass through a heating cavity 15 at a constant speed, controlling the temperature of the heating cavity 15 to be constant at 50 ℃, evaporating residual collecting liquid on the surfaces of the degradable polymer microspheres, and realizing automatic drying of the degradable polymer microspheres; the driving motor 18 of the powder brushing roller 20 is controlled to rotate at a constant speed of 120r/min, the degradable polymer microspheres completely dried on the stainless steel filter screen 12 are brushed down, the degradable polymer microspheres are collected into the powder collection tank 22 through the cyclone separator 25, automatic collection of the degradable polymer microspheres is achieved, and the degradable polymer microspheres refer to fig. 7.
Claims (9)
1. The utility model provides a high-efficient injection apparatus of medical degradable macromolecular material microballon, includes work platform (1), its characterized in that: a pair of dustproof motors (4) is arranged in the working platform (1), and the array type multiple spray heads (2) are arranged on the sliding table (3) of the dustproof motors (4); an annular electrode (6) is arranged under the array type multi-nozzle (2), and the annular electrode (6) is fixed on the working platform (1) through an annular electrode bracket (5) and an annular electrode lifting guide rail (29); a collector (9) is arranged right below the annular electrode (6); the array type multi-nozzle (2), the annular electrode (6) and the collector (9) are respectively connected with a channel I, a channel II and a grounding end of the high-voltage electrostatic generator (26); an electromagnetic straight-through valve (10) and a flat nozzle spray head (11) are installed at an outlet below the collector (9), a stainless steel filter mesh belt (12) is attached to the lower part of the flat nozzle spray head (11), and the stainless steel filter mesh belt (12) is driven by a stepping motor (17); a collected liquid recovery hopper (14) is arranged below the stainless steel filter mesh belt (12), an outlet of the collected liquid recovery hopper (14) is connected with an inlet of the gravity settling tank (13), an outlet of the gravity settling tank (13) is connected with an inlet of a reflux pump (16), an outlet of the reflux pump (16) is connected with a flushing nozzle (7), and the flushing nozzle (7) is arranged at the edge of the collector (9);
a heating cavity (15) is arranged on one side of a flat nozzle spray head (11), a stainless steel filter mesh belt (12) penetrates through the heating cavity (15), one end of the heating cavity (15) is tightly attached to a powder scraping roller (20), the powder scraping roller (20) is matched with the stainless steel filter mesh belt (12), the powder scraping roller (20) is tightly attached to an inlet of a collecting guide pipe (21), an outlet of the collecting guide pipe (21) is connected with an inlet of a cyclone separator (25), the cyclone separator (25) is fixed in a working platform (1) through a separator bracket (23), a smoke outlet of the cyclone separator (25) is connected with a draught fan, a discharge outlet of the cyclone separator (25) is connected with a powder collecting tank (22), and the powder collecting tank (22) is placed in the working platform (1); the powder brushing roller (20) is connected with a driving motor (18);
an FFU fan filter unit (30) and an air outlet efficient filter (24) are mounted on a shell of the working platform (1), and the FFU fan filter unit (30), the dustproof motor (4), the high-voltage electrostatic generator (26), the stepping motor (17) and the reflux pump (16) are connected with an industrial personal computer;
the array type multi-nozzle (2) comprises a needle cylinder (201), the needle cylinder (201) is arranged on a needle cylinder holder (202), and two sides below the needle cylinder holder (202) are fixed on the working platform (1) through a multi-nozzle support (203); the lower part of the needle cylinder (201) is connected with a needle cylinder bracket (204) capable of adjusting the height difference of the needle cylinders among layers, the needle cylinder bracket (204) is connected with a needle cylinder retainer (202) through a bearing bolt (206), and the outer side of the bearing bolt (206) is sleeved with a limit sleeve (207); the bottom of the needle cylinder (201) is connected with a stainless steel spray head (205).
2. The high-efficiency medical injection device of degradable polymer microspheres of claim 1, wherein: the stainless steel spray heads (205) are arranged in a concentric circumferential array layer-by-layer mode and are symmetrical along the connecting line from the central stainless steel spray head (205) to any stainless steel spray head (205); and obtaining the arrangement number of the stainless steel spray heads (205) in each layer according to the density maximization principle of the stainless steel spray heads (205).
3. The high-efficiency medical injection device of degradable polymer microspheres of claim 1, wherein: the syringe bracket (204) capable of adjusting the height difference of the syringes among the layers comprises a plurality of layers of syringe supporting plates and adjusting bolts for adjusting the height difference between the syringe supporting plates of the adjacent layers; the distance between the needle point of the stainless steel spray head (205) in the array type multi-spray head (2) and the receiver is adjusted to 10-50cm, and the adjusting bolts of all layers are adjusted to keep the electric field intensity at the needle point of the stainless steel spray head (205) of each layer under the same high pressure so as to achieve the effect of the synergistic and stable spraying of the stainless steel spray heads (205) of each layer.
4. The high-efficiency medical injection device of degradable polymer microspheres of claim 1, wherein: the adjustable height range of the annular electrode (6) relative to the collector (9) is 0-50cm, any one or more materials of a copper electrode, an aluminum electrode, a steel electrode and a composite conductive material are selected, the inner diameter range of the annular electrode changes along with the size of the outermost layer of the array type multi-nozzle (2), and the upper connection voltage changes along with the spraying voltage of the array type multi-nozzle (2) so as to restrict the spreading range of the degradable polymer microspheres sprayed by the array type multi-nozzle (2).
5. The high-efficiency medical injection device of degradable polymer microspheres of claim 1, wherein: the array type multi-nozzle (2) is supplied by a precise injection pump, a resorption type electric screw device and a charging barrel containing a precise extrusion device or an air pressure supply device adopting an air pump-air pressure controller-air distribution and discharge-charging barrel.
6. The high-efficiency medical injection device of degradable polymer microspheres of claim 1, wherein: collector (9) whole appearance be hourglass hopper-shaped, contain the collecting fluid and be used for buffering the microballon that high-speed flies to penetrate and down, collector (9) upper end opening diameter changes along with microballon dispersion scope, collector (9) lower extreme opening is the pipe thread interface of standard, the collecting fluid can wrap up and hold the microballon and flow from the lower extreme opening automatically when electromagnetism through valve (10) is opened.
7. The method for utilizing the medical degradable high polymer material microsphere high-efficiency injection device of claim 1 is characterized by comprising the following steps of:
1) a degradable polymer solution configured for electrostatic spraying;
2) the degradable polymer solution is subpackaged into each needle cylinder (201) of the array type multi-nozzle (2);
3) the method comprises the following steps of operating an FFU fan filter unit (30), operating a dustproof motor (4), adjusting the height between an array type multi-nozzle (2) and a collector (9), adjusting the height between an annular electrode (6) and the collector (9), adjusting the voltage applied to the array type multi-nozzle (2) and the voltage applied to the annular electrode (6) according to requirements, and realizing the cooperative stable spraying of a stainless steel nozzle (205) and the controllable deposition of degradable polymer microspheres;
4) running a control program, controlling an electromagnetic straight-through valve (10) to send the degradable polymer microspheres in the collector (9) to a stainless steel filter mesh belt (12) below through a flat nozzle spray head (11), filtering the collected liquid, flowing through a collected liquid recovery hopper (14) and entering a gravity settling tank (13), and realizing the automatic separation of the degradable polymer microspheres and the collected liquid; controlling the reflux pump (16) to pressurize and convey the collection liquid to the position of the scouring spray head (7) by the reflux pump (16) to scour the bottom of the collector (9) so as to prevent the degradable polymer microspheres from being adhered to each other; controlling a stepping motor (17) to enable a stainless steel filter mesh belt (12) to drive the degradable polymer microspheres to pass through a heating cavity (15) at a constant speed, evaporating residual collecting liquid on the surfaces of the degradable polymer microspheres, and realizing automatic drying of the degradable polymer microspheres; the powder brushing roller (20) is controlled to brush down the completely dried degradable polymer microspheres on the stainless steel filter mesh belt (12), and the degradable polymer microspheres are collected into a powder collecting tank (22) by a cyclone separator (25), so that the automatic collection of the degradable polymer microspheres is realized.
8. The method of claim 7, wherein: the degradable polymer solution is a hydrogel precursor solution, or the polyester polymer is dissolved in an organic solvent which is easy to evaporate and has no residue, and the concentration range of the solution is adjustable between 0.5 and 20w/v percent; the hydraulic precursor is polyvinyl alcohol copolymer, collagen, gelatin, sodium alginate or photocuring hydrogel; the polyester polymer is polycaprolactone, polylactic acid, polypropylene or polylactic acid-glycolic acid copolymer, and the organic solvent is acetic acid, dichloromethane or hexafluoroisopropanol.
9. The method of claim 8, wherein: determining a curing mode of the degradable polymer microspheres according to the properties of the degradable polymer material; when the degradable polymer solution is a hydrogel precursor solution, according to different crosslinking methods, curing the hydrogel precursor solution by controlling the temperature of a working space or adding ions for initiating crosslinking into a collection liquid or by adding a photoinitiator and installing a photocuring module to obtain hydrogel precursor microspheres; when the degradable polymer solution is polyester polymer solution, the evaporation of the solvent is accelerated by blowing fresh air or applying negative pressure or raising the temperature, and the solid polyester polymer microspheres are obtained.
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| CN112169697A (en) * | 2020-08-11 | 2021-01-05 | 江苏大学 | Integrated granulating system and method based on electrostatic atomization |
| CN112958305A (en) * | 2021-02-04 | 2021-06-15 | 南京微毫科技有限公司 | Electric field distribution control device, method and equipment for electrostatic spray nozzle array and computer storage medium |
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| CN112169697A (en) * | 2020-08-11 | 2021-01-05 | 江苏大学 | Integrated granulating system and method based on electrostatic atomization |
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