CN113559799B - A kind of high-efficiency spraying method and device of medical degradable polymer material microspheres - Google Patents

Abstract

A high-efficiency spraying method and device for medical degradable polymer material microspheres, comprising an array type multi-nozzle, 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 , The collector is connected to the high-voltage electrostatic generator; the outlet below the collector is equipped with a flat nozzle nozzle, the bottom of the flat nozzle nozzle is close to the stainless steel filter mesh belt, and there is a collection liquid recovery bucket under the filter mesh belt, the outlet of the collection liquid recovery bucket and the inlet of the gravity sedimentation tank The outlet of the gravity sedimentation tank is connected to the scouring nozzle through the return pump, and the scouring nozzle is arranged on the edge of the collector; the stainless steel filter mesh belt passes through the heating chamber, and the powder whisk roller cooperates with the stainless steel filter mesh belt. The outlet of the duct is connected with the inlet of the cyclone separator, the smoke outlet of the cyclone separator is connected with the induced draft fan, and the outlet of the cyclone separator is connected with the powder collecting tank; the invention realizes the efficient preparation, separation and drying of the medical degradable polymer material microspheres with collection.

Description

A kind of high-efficiency spraying method and device of medical degradable polymer material microspheres

technical field

The invention relates to the technical field of biological manufacturing and electrostatic spraying, in particular to a high-efficiency spraying method and device of medical degradable polymer material microspheres.

Background technique

Degradable macromolecular material microspheres are spheres made of biodegradable or resorbable macromolecular polymers, the diameter of which is usually in the range of micrometers or nanometers. Degradable polymer microspheres can coat small molecule drugs, biologically active macromolecules (such as proteins, enzymes, DNA) and even living cells, and have a wide range of application values in the fields of drug delivery, genetic engineering and tissue engineering.

The current preparation methods of degradable polymer material microspheres include emulsification method, spray drying method, microfluidic method, heating dispersion method and electrostatic spraying method. It is widely used in the manufacture of pure powder microspheres and core-shell microspheres because of its high purity. However, the yield of microspheres prepared by electrostatic spraying with a single nozzle on the market is low, and it is difficult to meet the requirements of large-scale applications.

At present, the electrostatic spraying system based on multiple nozzles has the following disadvantages:

The existing multi-nozzle arrangement scheme does not systematically study the problem of maximizing the arrangement density of the nozzles, and has the limitation of low space utilization;

The existing multi-nozzle arrangement schemes mostly use linear arrangement, rectangular array, hexagonal array, etc. The electric field strength of the central nozzle is low, and the electric field strength of the peripheral nozzle is high. There is a large difference in the electric field strength of the inner and outer nozzles, which leads to different spraying states of the inner and outer nozzles. This leads to the problem of large deviations in the morphology and size of the microspheres;

The existing multi-nozzle electrostatic spray mostly uses a syringe pump and multi-branch flow channels for liquid supply, and manufacturing and assembly errors easily lead to uneven flow rates among the nozzles, resulting in large differences in the morphology and size of the prepared microspheres;

At present, there is no automatic separation and collection device for electrostatically sprayed microspheres on the market, and manual collection will increase the risk of introducing impurities and contamination.

SUMMARY OF THE INVENTION

In order to overcome the above-mentioned shortcomings of the prior art, the purpose of the present invention is to provide a high-efficiency injection method and device for medical degradable polymer material microspheres, which solves the problem that the electric field strength of the needle tip in different regions of the array needle varies greatly when the voltage is applied. , and the problem of the large range of sprayed droplets that are difficult to collect, not only can realize the efficient preparation of medical degradable polymer microspheres, but also realize the automatic separation, drying and collection of microspheres, which greatly expands the application capability of this technology.

To achieve the above object, the technical scheme adopted in the present invention is:

A high-efficiency spraying device for medical degradable polymer material microspheres, comprising a working platform 1, a pair of dust-proof motors 4 are arranged in the working platform 1, and an array type multi-spray head 2 is installed on a sliding table 3 of the dust-proof motor 4; A ring-shaped electrode 6 is arranged directly below the multi-nozzle 2, and the ring-shaped electrode 6 is fixed on the working platform 1 through the ring-shaped electrode support 5 and the ring-shaped electrode lifting guide 29; a collector 9 is arranged directly below the ring-shaped electrode 6; Type multi-spray head 2, annular electrode 6, collector 9 are respectively connected with channel 1, channel 2 and grounding end of high-voltage electrostatic generator 26; electromagnetic straight-through valve 10 and flat nozzle nozzle 11 are installed at the outlet below collector 9, flat nozzle The bottom of the nozzle 11 is close to the stainless steel filter mesh belt 12, and the stainless steel filter mesh belt 12 is driven by a stepper motor 17; the stainless steel filter mesh belt 12 is provided with a collection liquid recovery bucket 14, the outlet of the collection liquid recovery bucket 14 and the gravity sedimentation tank 13 The entrance Connected, the outlet of the gravity sedimentation tank 13 is connected with the inlet of the return pump 16, the outlet of the return pump 16 is connected to the flushing nozzle 7, and the flushing nozzle 7 is arranged on the edge of the collector 9;

A heating chamber 15 is installed on one side of the flat nozzle nozzle 11, the stainless steel filter mesh belt 12 passes through the heating chamber 15, and one end of the heating chamber 15 is close to the powder brushing roller 20. The roller 20 is close to the inlet of the collection duct 21, the outlet of the collection duct 21 is connected with the inlet of the cyclone separator 25, the cyclone separator 25 is fixed in the working platform 1 through the separator bracket 23, and the smoke outlet of the cyclone separator 25 is connected with the induced draft fan , the discharge port of the cyclone separator 25 is connected with the powder collecting tank 22, and the powder collecting tank 22 is placed in the working platform 1; the powder whisking roller 20 is connected with the driving motor 18;

The FFU fan filter unit 30 and the air outlet high-efficiency filter 24 are installed on the shell of the working platform 1, the FFU fan filter unit 30, the dust-proof motor 4, the high-voltage electrostatic generator 26, the air pressure controller 27, the stepper motor 17, and the return pump 16. All are connected to the industrial computer.

The array type multi-nozzle 2 includes a needle cylinder 201, the needle cylinder 201 is installed on the needle cylinder holder 202, and the lower sides of the needle cylinder holder 202 are fixed on the working platform 1 through the multi-nozzle bracket 203; the lower part of the needle cylinder 201 Connected to the needle cylinder bracket 204 that can adjust the height difference of the needle cylinder between layers, the needle cylinder bracket 204 and the needle cylinder holder 202 are connected by a load-bearing bolt 206, and the outer side of the load-bearing bolt 206 is covered with a limiting sleeve 207; the needle cylinder 201 A stainless steel nozzle 205 is connected to the bottom.

The stainless steel nozzles 205 are arranged in a concentric circular array level, and are symmetrical along the line connecting the central stainless steel nozzle 205 to any stainless steel nozzle 205; according to the principle of maximizing the density of the stainless steel nozzles 205, the number of stainless steel nozzles 205 arranged in each layer is obtained.

The syringe bracket 204 that can adjust the height difference of the syringes between layers includes a multi-layer syringe support plate, and an adjustment bolt for adjusting the height difference between the adjacent layers of syringe support plates; The distance between the needle tip of the stainless steel nozzle 205 and the receiver is adjusted to 10-50cm, and the adjustment bolts of each layer are adjusted so that the electric field strength at the needle tip of the stainless steel nozzle 205 at each level is consistent under the same high pressure, so as to achieve the coordinated and stable spraying of the stainless steel nozzle 205 at each level. effect.

The adjustable range of the annular electrode 6 relative to the collector 9 is 0-50 cm, and any one or several materials of copper electrodes, aluminum electrodes, steel electrodes, and composite conductive materials are selected. The size of the outermost layer changes, and the voltage connected to it varies with the ejection voltage of the array-type multi-jet head 2 to constrain the dispersion range of the microspheres ejected by the array-type multi-jet head 2 .

Use a precision injection pump, a back-suction electric screw device, a barrel containing a precision extrusion device, or a pneumatic liquid supply device using an air pump-air pressure controller-air separation and discharge-barrel to feed the array type multi-nozzle 2.

The overall shape of the collector 9 is in the shape of a funnel, and the collector 9 is filled with a collection liquid for buffering the microspheres flying down at a high speed. With a standard pipe thread interface, the collected liquid can be wrapped around the microspheres and automatically flow out from the lower end opening when the electromagnetic straight-through valve 10 is opened.

The heating chamber 15 is made of aluminum alloy, and the temperature of the heating chamber 15 is controlled by a temperature-controlled heater to keep constant, and the temperature adjustment range is 25-210 degrees Celsius.

The adjustable voltage amplitude of the high-voltage electrostatic generator 26 is 0-50KV.

Utilize a kind of high-efficiency spraying method and device of medical degradable polymer material microspheres, comprising the following steps:

1) Configure the degradable polymer solution for electrostatic spraying;

2) Distributing the degradable polymer solution into each syringe 201 of the array type multi-spray head 2;

3) Run the FFU fan filter unit 30, run the dust-proof stepper motor 4, adjust the height of the array type multi-spray head 2 from the collector 9, adjust the height of the ring electrode 6 from the collector 9, and adjust the height of the array type multi-spray head according to the needs. The voltage on 2, the voltage applied on the ring electrode 6, realizes the coordinated stable spraying of the stainless steel nozzle 205 and the controllable deposition of the microspheres;

4) Run the control program, control the electromagnetic two-way valve 10 to send the degradable polymer microspheres in the collector 9 to the stainless steel filter screen 12 below through the flat nozzle nozzle 11, and the collected liquid flows through the collection liquid recovery hopper after being filtered. 14 enters the gravity sedimentation tank 13 to realize the automatic separation of the degradable polymer microspheres and the collection liquid; control the return pump 16 to make the collection liquid pressurized and transported to the flushing nozzle 7 by the reflux pump 16 to flush the bottom of the collector 9 to prevent The degradable polymer microspheres are adhered to each other; the stepper motor 17 is controlled to make the stainless steel filter screen 12 drive the degradable polymer microspheres to pass through the heating chamber 15 at a uniform speed, and the residual collection liquid on the surface of the degradable polymer microspheres is evaporated to realize degradable polymerization. The degradable polymer microspheres are automatically dried by controlling the powder brushing roller 20 to brush the completely dried degradable polymer microspheres on the stainless steel filter screen 12, and the degradable polymer microspheres are collected by the cyclone separator 25 into the powder collecting tank 22 to realize Automated collection of degradable polymer microspheres.

The degradable polymer solution is a hydraulic precursor solution, or a polyester polymer is dissolved in an organic solvent that is easy to evaporate and has no residue, and the solution concentration range is adjustable between 0.5-20w/v%; water Condensed precursors are polyvinyl alcohol copolymer, collagen, gelatin, sodium alginate or light-cured hydrogel; polyester polymers are polycaprolactone, polylactic acid, polypropylene or polylactic acid-glycolic acid copolymer, The organic solvent is acetic acid, dichloromethane or hexafluoroisopropanol.

According to the properties of the degradable polymer material, the curing method of the degradable polymer microspheres is determined; when the degradable polymer solution is a hydraulic precursor solution, according to the different cross-linking methods, by controlling the temperature of the working space or at the Add ions that initiate crosslinking to the collection solution or solidify the hydrogel precursor solution by adding a photoinitiator-installing a light curing module to obtain hydrogel precursor microspheres; when the degradable polymer solution is polyester When the polymer-like solution is prepared, the evaporation of the solvent is accelerated by blowing in fresh air or applying negative pressure or increasing the temperature to obtain solid polyester-like polymer microspheres.

When the degradable polymer microspheres are hydrogel precursor microspheres, run the control program to control the 10-degree opening of the electromagnetic two-way valve or periodically turn on and off, and use gravity, vibration, pumping or scouring, and collection liquid transportation. , the collection liquid and the hydrogel precursor microspheres in the collector 9 are directly transported to the gravity sedimentation tank 13 to realize the automatic collection of the hydrogel precursor microspheres.

When the degradable polymer microspheres are polyester polymer microspheres, run the control program to control the 10-degree opening of the electromagnetic two-way valve or periodically turn on and off, and use gravity, vibration, pumping or scouring, and collecting liquid to carry. The collected liquid and polyester polymer microspheres in the collector 9 are sent to the stainless steel filter screen 12 below, and the collected liquid enters the gravity settling tank 13 after being filtered, and the polyester polymer microspheres are retained on the stainless steel filter screen. On 12, the automatic separation of polyester polymer microspheres and the collection liquid is realized; the return pump 16 is controlled to work periodically, the collection liquid is transported back to the collector 9 by the return pump 16 under pressure, and the collection liquid flushes the bottom of the collector 9 , to prevent the polyester polymer microspheres from adhering to each other; control the stepper motor 17 to drive the stainless steel filter screen 12 to rotate at a constant speed, and drive the polyester polymer microspheres to pass through the heating chamber 15 at a constant speed, and collect the residual surface of the polyester polymer microspheres. The liquid is completely removed, and the automatic drying of degradable polymer microspheres is realized; the driving motor 18 of the powder dusting roller is controlled to rotate at a constant speed, and the completely dried polyester polymer microspheres on the stainless steel filter screen 12 are brushed down, and the cyclone separator 25 The degradable polymer microspheres are collected into the powder collecting tank 22 to realize the automatic collection of the polyester polymer microspheres.

Compared with the prior art, the beneficial effects of the present invention are:

1) The density of the stainless steel nozzles 205 of the device of the present invention is maximized, and the efficiency of the arrangement of multiple nozzles is maximized.

2) The array-type multi-nozzle of the device of the present invention adopts the needle cylinder bracket 204 that can adjust the height difference of the needle cylinder between layers, instead of the traditional single-height multi-nozzle arrangement, and realizes the electric field at the needle tips of multiple stainless steel nozzles 205 under the same voltage. The strength is basically the same.

3) The present invention uses air pressure liquid supply instead of traditional syringe pump liquid supply, effectively controls the flow rate of each stainless steel nozzle 205 to be basically the same, and realizes simultaneous coordinated and stable spraying of multiple stainless steel nozzles 205 .

4) The device of the present invention realizes automatic separation, drying and collection of degradable polymer microspheres, and at the same time ensures that the whole process of preparation-separation-drying-collection of medical degradable polymer microspheres is in a clean environment; The large-scale application of spheres in biomanufacturing and biomedical fields is of great significance.

Description of drawings

Figure 1 is a schematic diagram of the structure of the device of the present invention.

Fig. 2 is a bottom view of an array type multi-spray head according to an embodiment of the present invention.

FIG. 3 is a front view of an array type multi-spray head according to an embodiment of the present invention.

FIG. 4 is a schematic structural diagram of an array-type syringe carrier according to an embodiment of the present invention.

FIG. 5 compares the results of finite element analysis of the electric field intensity between the array type multi-nozzle of the embodiment of the present invention and the traditional array type multi-nozzle.

Fig. 6 Finite element analysis results of electric field confinement of degradable polymer microspheres by ring electrodes according to an embodiment of the present invention.

FIG. 7 is a microscope view of the degradable polymer microspheres prepared in the embodiment of the present invention.

Detailed ways

The present invention will be further described in detail below with reference to the embodiments and accompanying drawings. It should be noted that the following detailed descriptions are all exemplary, and are intended to provide further explanation of the present invention. Unless otherwise defined, all technical and scientific terms used have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

It should be noted that the terminology used herein is for describing specific embodiments only, and is not intended to limit the present invention. As used herein, unless the context clearly dictates otherwise, the singular is intended to include the plural as well, furthermore, it is to be understood that when the terms "comprising" and/or "including" are used in this specification, it indicates that There are features, steps, operations, devices, components and/or combinations thereof. The present embodiment and the features in the embodiment may be combined with each other without conflict.

As shown in FIG. 1 , a high-efficiency spraying device for medical degradable polymer material microspheres includes a working platform 1, and a pair of dust-proof motors 4 are arranged in the working platform 1, and an array type is installed on the sliding table 3 of the dust-proof motors 4 Multi-nozzle 2, the array type multi-nozzle 2 can move up and down relying on the dust-proof motor 4; the array-type multi-nozzle 2 is connected to the air distributor 28 and the air pressure controller 27 in turn through the air pipe, and the air distributor 28 and the air pressure controller 27 are fixed in the working position. On the platform 1; an annular electrode 6 is arranged directly under the array type multi-nozzle 2, the annular electrode 6 is installed on the annular electrode lifting guide 29 through the annular electrode bracket 5, and the annular electrode lifting guide 29 is fixed on the working platform 1. , the ring electrode 6 can adjust the height up and down; the collector 9 is arranged directly under the ring electrode 6, and the collector 9 is fixed in the working platform 1; Channel 1, channel 2, and grounding end of the electrostatic generator 26 are connected; an electromagnetic straight-through valve 10 and a flat nozzle nozzle 11 are installed at the outlet below the collector 9, and the bottom of the flat nozzle nozzle 11 is close to the stainless steel filter mesh belt 12, and the stainless steel filter mesh belt 12 follows The synchronous belt on the pulley moves synchronously, and the pulley is connected with the stepper motor 17; the stainless steel filter mesh belt 12 is provided with a collection liquid recovery bucket 14, and the outlet of the collection liquid recovery bucket 14 is connected to the inlet of the gravity settling tank 13. The gravity settling tank 13 The outlet is connected to the inlet of the return pump 16, the outlet of the return pump 16 is connected to the flushing nozzle 7, and the flushing nozzle 7 is arranged on the edge of the collector 9;

A heating chamber 15 is installed on the left side of the flat nozzle nozzle 11 , the stainless steel filter mesh belt 12 passes through the heating chamber 15 , the left end of the heating chamber 15 is close to the powder whisking roller 20 , and the powder whisking roller 20 is fixed on the working platform through the filter screen mounting plate 19 1, the powder whisking roller 20 is matched with the stainless steel filter mesh belt 12, the left side of the powder whisking roller 20 is close to the inlet of the collecting duct 21, the outlet of the collecting duct 21 is connected with the inlet of the cyclone separator 25, and the cyclone separator 25 passes through the separator bracket 23. The upper part is fixed in the working platform 1, the exhaust port of the cyclone separator 25 is connected with the induced draft fan, the discharge port of the cyclone separator 25 is connected with the powder collecting tank 22, and the powder collecting tank 22 is placed in the working platform 1; connected with the drive motor 18;

The FFU fan filter unit 30 and the air outlet high-efficiency filter 24 are installed on the shell of the working platform 1, the FFU fan filter unit 30, the dust-proof motor 4, the high-voltage electrostatic generator 26, the air pressure controller 27, the stepper motor 17, and the return pump 16. All are connected to the industrial computer.

2 and 3, the array type multi-spray head 2 includes a syringe 201, the syringe 201 is mounted on the syringe holder 202, and the two sides of the lower side of the syringe holder 202 pass through insulating gaskets 208 and multi-nozzle brackets 203 It is fixed on the working platform 1; the lower part of the needle cylinder 201 is connected to the needle cylinder bracket 204 which can adjust the height difference of the needle cylinder between layers. The outer side of the bolt 206 is covered with a limit sleeve 207; the bottom of the needle cylinder 201 is connected with a stainless steel nozzle 205;

The stainless steel nozzles 205 are arranged in a concentric circular array, and are symmetrical along the line connecting the central stainless steel nozzle 205 to any stainless steel nozzle 205; The minimum spacing L should be greater than 32mm, that is, when min{L1, L2, L3} ≥ 32, according to the principle of maximizing the density of stainless steel nozzles 205 (the number of stainless steel nozzles 205 per unit area: pcs/mm2), 205 rows of stainless steel nozzles per layer are obtained. The number of cloths is 1-6-12-12-24 (take five layers as an example), at this time, the distribution diameter of the outermost stainless steel nozzle 205 is rounded to 245mm.

Referring to FIG. 4 , the syringe bracket 204 (taking five layers as an example) that can adjust the height difference of the syringes between layers includes a first-layer needle-cylinder support plate 204-1, a second-layer needle-cylinder support plate 204-2, and a third-layer needle-cylinder support plate 204-2. 204-3, 204-4, 204-4, 204-5, 204-5, 204-5, 204-4, 204-4, 204, 204 The first adjusting bolt 204-6 for the height difference between -5, the second adjusting bolt 204-7 for adjusting the height difference between the three-layer needle cylinder support plate 204-3 and the four-layer needle cylinder support plate 204-4, A third adjusting bolt 204-8 for adjusting the height difference between the second-layer needle cylinder support plate 204-2 and the third-layer needle cylinder support plate 204-3, for adjusting the first-layer needle cylinder support plate 204-1 and the second-layer needle cylinder support plate 204-1 The fourth adjusting bolt 204-9 for the height difference between the needle cylinder support plates 204-2; the distance between the needle tip 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 make the application Under the same high pressure, the electric field strength at the needle tip of each level of stainless steel nozzles 205 remains basically the same (as shown in Figure 5), so as to achieve the effect of coordinated and stable injection of stainless steel nozzles 205 at all levels, while the traditional nozzle arrangement of equal height shows obvious The problem that the electric field strength of the outer layer is greater than that of the inner layer.

As shown in FIG. 6 , the annular electrode 6 is located directly below the array type multi-spray head 2, and the height relative to the collector 9 is adjusted to 20 cm. The inner diameter of the annular electrode 6 is 30 cm. Copper electrodes, aluminum electrodes, steel electrodes, Any one or several materials of the composite conductive material; the upper voltage is 27kv with the multi-nozzle spray, and the existence of the ring electrode 6 significantly reduces the powder dispersion range from 1.07E5 mm ² to 8.5E4 mm compared with no ring electrode 6 ² , to constrain the dispersion range of the microspheres ejected by the array type multi-nozzle 2 to reduce the waste of raw materials.

Use a precision injection pump, a back-suction electric screw device, a barrel containing a precision extrusion device, or a pneumatic liquid supply device using an air pump-air pressure controller-air separation and discharge-barrel to feed the array type multi-nozzle 2, it is preferred to use The air pressure liquid supply device avoids the unavoidable uneven problem of the liquid dispensing type of the syringe pump, and realizes the uniform injection volume.

The collector 9 is located directly below the array type multi-nozzle 2 and the ring electrode 6, and the overall shape is funnel-shaped, and a certain amount of collecting liquid is filled in it for buffering the microspheres flying down at high speed, collecting The opening diameter of the upper end of the collector 9 varies with the dispersion range of the microspheres. The opening of the lower end of the collector 9 is a standard pipe thread interface of 1/2 inch inch thread, the inner diameter of the nozzle is 18mm, and the taper of the collector 9 is 10:1. When the valve 10 is opened, the microspheres can be wrapped around and automatically flow out from the opening at the lower end.

The heating cavity 15 is made of aluminum alloy with good thermal conductivity, and the temperature of the heating cavity 15 is controlled by a temperature control heater to keep constant. In this embodiment, polycaprolactone microspheres (melting point 60 degrees Celsius) are prepared, so the temperature is adjusted To 40 degrees Celsius, to prevent the microspheres from melting or deforming, the stainless steel filter screen 12 passes through the heating chamber 15, and the residual collected liquid in the microspheres evaporates to obtain dry microspheres.

The adjustable voltage amplitude of the high-voltage electrostatic generator 26 is 0-50KV.

Using a method of a high-efficiency spray device for medical degradable polymer material microspheres, the degradable polymer solution driven by high-voltage static electricity forms a Taylor cone spray at the array multi-nozzle head, and the discharged charged droplets are subjected to electrostatic repulsion greater than Surface tension, which in turn breaks into smaller charged droplets, involves the following steps:

1) Configure a degradable polymer solution, the degradable polymer solution is a degradable polycaprolactone solution with a concentration of 8w/v%, and the solvent is dichloromethane;

2) Distributing the degradable polymer solution into each syringe 201 of the array type multi-spray head 2;

3) Run the FFU fan filter unit 30, run the dust-proof stepper motor 4, adjust the height of the array type multi-nozzle 2 from the collector 9 to 20cm, adjust the height of the ring electrode 6 from the collector 9 to 20cm, and adjust the height according to the needs. The voltage on the array type multi-nozzle 2 is 40KV, and the voltage applied on the ring electrode 6 is 28KV, realizing the coordinated stable spraying of 55 stainless steel nozzles 205 and the controllable deposition of degradable polymer microspheres;

4) Run the control program, control the electromagnetic two-way valve 10 to open for 15 seconds every 15 seconds, and use gravity and the conveying action of the collecting liquid to send the degradable polymer microspheres in the collector 9 to the bottom through the flat nozzle nozzle 11. On the stainless steel filter screen 12, the collected liquid flows through the collection liquid recovery bucket 14 into the gravity settling tank 13 after being filtered, and realizes the automatic separation of the degradable polymer microspheres and the collected liquid; control the return pump 16 to work every 25 seconds For 5 seconds, the collected liquid is pressurized and transported to the flushing nozzle 7 by the return pump 16, and the high-pressure collected liquid flushes the bottom of the collector 9 to prevent the degradable polymer microspheres from adhering to each other; the stepping motor 17 that controls the driving pulley to 10r The stainless steel filter screen 12 moves synchronously with the synchronous belt, and drives the degradable polymer microspheres to pass through the heating chamber 15 at a constant speed. Evaporate to realize automatic drying of the degradable polymer microspheres; control the driving motor 18 of the powder whisking roller 20 to rotate at a constant speed of 120 r/min, and brush the completely dried degradable polymer microspheres on the stainless steel filter screen 12. The separator 25 collects the degradable polymer microspheres into the powder collecting tank 22 to realize the automatic collection of the degradable polymer microspheres. Refer to FIG. 7 for the degradable polymer microspheres.

Claims (9)

1. A high-efficiency injection device for medical degradable polymer material microspheres, comprising a working platform (1), characterized in that: a pair of dust-proof motors (4) are provided in the working platform (1), and a pair of dust-proof motors (4) are provided in the working platform (1). An array-type multi-nozzle (2) is installed on the sliding table (3) of the device; an annular electrode (6) is arranged directly under the array-type multi-nozzle (2), and the annular electrode (6) passes through the annular electrode bracket (5), the annular electrode The electrode lifting guide rail (29) is fixed on the working platform (1); a collector (9) is arranged directly below the annular electrode (6); the array type multi-nozzle (2), the annular electrode (6), the collector (9) are respectively connected with channel 1, channel 2 and grounding end of the high-voltage electrostatic generator (26); an electromagnetic straight-through valve (10) and a flat nozzle nozzle (11) are installed at the outlet below the collector (9), and the flat nozzle nozzle ( 11) The bottom is close to the stainless steel filter mesh belt (12), and the stainless steel filter mesh belt (12) is driven by the stepping motor (17); the stainless steel filter mesh belt (12) is provided with a collection liquid recovery bucket (14) below the collection liquid recovery bucket The outlet of (14) is connected to the inlet of the gravity sedimentation tank (13), the outlet of the gravity sedimentation tank (13) is connected to the inlet of the return pump (16), and the outlet of the return pump (16) is connected to the flushing nozzle (7), which is connected to the flushing nozzle (7). ) is arranged on the edge of the collector (9); A heating chamber (15) is installed on one side of the flat nozzle nozzle (11), the stainless steel filter mesh belt (12) passes through the heating chamber (15), and one end of the heating chamber (15) is close to the powder whisk roller (20), The roller (20) cooperates with the stainless steel filter mesh belt (12), the powder whisking roller (20) is closely attached to the inlet of the collecting duct (21), and the outlet of the collecting duct (21) is connected with the inlet of the cyclone separator (25), and the cyclone separator ( 25) It is fixed in the working platform (1) through the separator bracket (23), the exhaust port of the cyclone separator (25) is connected with the induced draft fan, and the discharge port of the cyclone separator (25) is connected with the powder collecting tank (22). , the powder collecting tank (22) is placed in the working platform (1); the powder whisking roller (20) is connected with the driving motor (18); The FFU fan filter unit (30) and the air outlet high-efficiency filter (24), the FFU fan filter unit (30), the dust-proof motor (4), the high-voltage electrostatic generator (26), the step The inlet motor (17) and the return pump (16) are all connected with the industrial computer; The array type multi-nozzle (2) comprises a needle cylinder (201), the needle cylinder (201) is mounted on the needle-cylinder holder (202), and the lower two sides of the needle-cylinder holder (202) pass through the multi-nozzle bracket (203) It is fixed on the working platform (1); the lower part of the needle cylinder (201) is connected to the needle cylinder bracket (204) which can adjust the height difference of the needle cylinder between layers, the needle cylinder bracket (204) and the needle cylinder holder (202) ) are connected by load-bearing bolts (206), and the outer side of the load-bearing bolts (206) is covered with a limiting sleeve (207); the bottom of the needle cylinder (201) is connected with a stainless steel nozzle (205). 2. The high-efficiency spray device for medical degradable polymer material microspheres according to claim 1, characterized in that: the stainless steel spray heads (205) are arranged in a concentric circle array level, and along the center stainless steel spray head (205) The connection line to any stainless steel nozzle (205) is symmetrical; according to the principle of maximizing the density of the stainless steel nozzle (205), the number of stainless steel nozzles (205) arranged in each layer is obtained. 3. The high-efficiency injection device for medical degradable polymer material microspheres according to claim 1, characterized in that: the syringe bracket (204) that can adjust the height difference of the syringes between layers comprises a multi-layer needle Cylinder support plate, and adjustment bolts for adjusting the height difference between adjacent layers of needle cylinder support plates; in the array type multi-spray head (2), the distance between the needle tip of the stainless steel spray head (205) and the receiver is adjusted to 10-50cm. Adjusting the bolts at each layer keeps the electric field strengths at the needle tips of the stainless steel nozzles (205) at all levels consistent under the same high pressure, so as to achieve the coordinated and stable spraying effect of the stainless steel nozzles (205) at all levels. 4. The high-efficiency injection device for medical degradable polymer material microspheres according to claim 1, characterized in that: the adjustable height range of the annular electrode (6) relative to the collector (9) is 0 -50cm, choose any one or several materials of copper electrode, aluminum electrode, steel electrode, composite conductive material, the inner diameter range varies with the outermost layer size of the array type multi-spray head (2), and the upper voltage varies with the array type multi-spray head (2). 2) The spray voltage is changed to constrain the dispersion range of the degradable polymer microspheres sprayed by the array type multi-spray head (2). 5. A kind of high-efficiency injection device for medical degradable macromolecular material microspheres according to claim 1, it is characterized in that: adopt precision syringe pump, back-suction electric screw device, barrel containing precision extrusion device or adopt air pump - Air pressure controller - Air distribution and discharge - The air pressure liquid supply device of the barrel supplies material for the array type multi-nozzle (2). 6. A kind of high-efficiency injection device for medical degradable polymer material microspheres according to claim 1, characterized in that: the overall shape of the collector (9) is funnel-shaped, and a collection liquid is filled in it for high-speed The microspheres flying down are buffered, the diameter of the upper end opening of the collector (9) varies with the dispersion range of the microspheres, the lower end opening of the collector (9) is a standard pipe thread interface, and the collected liquid is opened when the electromagnetic straight-through valve (10) is opened It can automatically flow out from the lower end opening with the microspheres encased in it. 7. the method that utilizes a kind of medical degradable macromolecular material microsphere high-efficiency injection device according to claim 1, is characterized in that, comprises the following steps: 1) Configure the degradable polymer solution for electrostatic spraying; 2) Distributing the degradable polymer solution into each syringe (201) of the array type multi-spray head (2); 3) Run the FFU fan filter unit (30), run the dust-proof motor (4), adjust the height of the array type multi-nozzle (2) from the collector (9), and adjust the distance between the ring electrode (6) and the collector (9). Height, adjust the voltage applied to the array type multi-jet head (2) and the voltage applied to the ring electrode (6) according to the requirements, so as to realize the coordinated and stable jetting of the stainless steel jet head (205) and the controllable control of the degradable polymer microspheres deposition; 4) Run the control program, and control the electromagnetic straight-through valve (10) to send the degradable polymer microspheres in the collector (9) to the stainless steel filter mesh belt (12) below through the flat nozzle nozzle (11), and the collected liquid is passed through. After filtering, it flows through the collection liquid recovery hopper (14) and enters the gravity settling tank (13) to realize the automatic separation of the degradable polymer microspheres and the collection liquid; the reflux pump (16) is controlled so that the collection liquid is added by the reflux pump (16). The pressure is conveyed to the flushing nozzle (7), and the bottom of the collector (9) is flushed to prevent the degradable polymer microspheres from adhering to each other; the stepper motor (17) is controlled to make the stainless steel filter mesh belt (12) drive the degradable polymer microspheres. The balls pass through the heating chamber (15) at a uniform speed to evaporate the residual collection liquid on the surface of the degradable polymer microspheres, so as to realize automatic drying of the degradable polymer microspheres; control the powder whisking roller (20) to completely cover the stainless steel filter mesh belt (12). Under the brush of the dried degradable polymer microspheres, the degradable polymer microspheres are collected by the cyclone (25) into the powder collecting tank (22), so as to realize the automatic collection of the degradable polymer microspheres. 8. The method according to claim 7, wherein the degradable polymer solution is a hydrogel precursor solution, or a polyester polymer is dissolved in an organic solvent that is easy to evaporate and has no residue, and the solution The concentration range is adjustable between 0.5-20w/v%; the hydraulic precursor is polyvinyl alcohol copolymer, collagen, gelatin, sodium alginate or light-cured 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 according to claim 8, characterized in that: according to the properties of the degradable polymer material, the solidification mode of the degradable polymer microspheres is determined; when the degradable polymer solution is a hydrogel precursor solution , depending on the cross-linking method, by controlling the temperature of the working space or adding ions that initiate cross-linking in the collection solution, or by adding a photoinitiator-installing a photocuring module, the hydrogel precursor solution is cured to obtain a hydrogel. Glue-based precursor microspheres; when the degradable polymer solution is a polyester-based polymer solution, the evaporation of the solvent is accelerated by blowing fresh air or applying negative pressure or increasing the temperature to obtain solid polyester-based polymer microspheres. ball.

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