An automated preparation machine for gas-containing microsphere injection solutions

Abstract

This invention discloses an automated preparation machine for gas-containing microsphere injection solutions. The machine frame includes a main worktable, a clean laminar flow system located above the frame, and an ultrasonic container support positioned in the center of the main worktable. An ultrasonic container is mounted on the support, with a silicone tube connected to its lower end. The lower end of the silicone tube connects to the upper end of a T-junction. One end of the T-junction is connected to an air inlet system via a No. 2 clamp valve, and the other end is connected to a liquid extraction system. An ultrasonic head support is mounted on the main worktable behind the ultrasonic container support, and includes an ultrasonic head and a temperature probe. The outlet of the raw material feeding system is connected to the ultrasonic container. The liquid extraction system is mounted on the main worktable below the raw material feeding system, and the air inlet system is mounted on the side of the frame. This invention significantly reduces manual operation, achieves thorough cleaning, improves preparation efficiency and liquid surface stability during preparation, and avoids problems such as premature emulsification introducing air.

Description

Technical Field

[0001] This invention relates to the field of equipment technology, and more specifically, to an automated preparation machine for gas-containing microsphere injection solutions. Background Technology

[0002] Microspheres are tiny spherical entities formed when drugs are dissolved or dispersed in polymeric materials. They have a diameter of approximately 1–250 μm and belong to matrix-type skeletal microparticles.

[0003] Micron-sized microspheres can be produced by using ultrasound of a certain intensity to treat a solution containing foaming components, while simultaneously introducing an inert gas (see the literature [Cory Berkland, Kyekoon (Kevin) Kim, Daniel W. Pack, J. Control Release. 73 (2001), 59-74)]. This literature discloses an ultrasonic vibration excitation device that uses a frequency generator to vibrate a nozzle at a certain frequency to prepare microspheres. These microspheres can be used as sterile injectable ultrasound contrast agents in vivo, which has important application significance in the field of medical imaging.

[0004] Currently, the applicant's microsphere injection solution is produced under completely sterile conditions. The main production steps are: adding raw materials (human leukoplakia and sodium chloride injection), preheating, introducing inert gas, ultrasonication while introducing inert gas, continuing ultrasonication, and terminating ultrasonication at a certain temperature. Production in the workshop is entirely manual. The laboratory currently has an ultrasonic microsphere preparation device (patent number: CN206262507U), which mainly solves the problems of fixing the ultrasonic container, adding materials, and stabilizing gas flow. However, this device still has certain shortcomings, as detailed below:

[0005] 1. Existing ultrasonic microsphere preparation devices have two liquid inlets at the cross-section of the ultrasonic container expansion body. During repeated preparation and cleaning processes, it is impossible to thoroughly rinse the ultrasonic container, ultrasonic head, and temperature probe. At the same time, the waste liquid is discharged slowly by gravity. When the waste liquid is discharged, the microspheres and other foam floating on the surface of the waste liquid will adhere to the surface of the ultrasonic container, ultrasonic head, and temperature probe as the liquid level drops, resulting in incomplete cleaning.

[0006] 2. The prepared microsphere suspension and waste liquid are discharged through a single pipe. The advantage is that it can achieve better cleaning effect on the ultrasonic container and the interface between the ultrasonic container and the pipe during cleaning. However, the flow direction of the microsphere suspension and waste liquid is selected by manually pulling the tube at the outlet. Improper manual operation can cause the microsphere suspension and waste liquid to be mixed. In the aseptic production process, the biggest source of contamination is "human". The possibility of contamination caused by human operation exceeds 70%, and the risk of aseptic operation by manually pulling the tube is high.

[0007] 3. The ultrasonic container, air intake system, and liquid drainage system are connected by a three-way valve. The connecting pipe between the ultrasonic container and the three-way valve is quite long. The raw material in the ultrasonic container flows through the pipe to the three-way valve. During preparation, the gas forces the liquid in the pipe back into the ultrasonic container. After the air intake stops, the liquid flows back into the pipe, causing the liquid level in the ultrasonic container to change with the air intake. This makes it impossible to guarantee the depth to which the ultrasonic head penetrates the liquid surface, significantly affecting the ultrasonic emulsification effect of the raw material. Furthermore, the raw material flowing into the pipe during the preparation process is not effectively ultrasonically prepared, resulting in the presence of unprepared raw material in the finished microsphere suspension. Additionally, each preparation requires multiple manual interventions to select the opening direction of the three-way valve, posing a high risk to aseptic technique.

[0008] The ultrasonic probe is inserted into and fixed in the ultrasonic container. However, during the preparation process, it is not possible to automatically raise or lower the ultrasonic head according to process requirements to change the depth of the ultrasonic head probing below the liquid surface. When ultrasonication is performed at the depth of ultrasonic ventilation during the preheating process, air on the liquid surface may be introduced into the liquid, prematurely emulsifying some raw materials to form air-encapsulated microspheres, which are not inert gas-containing microspheres, resulting in unqualified products.

[0009] Therefore, it is necessary to improve the current technology and develop an automated preparation machine for gas-containing microsphere injection solutions to solve problems such as excessive manual operation, incomplete cleaning, some raw materials entering the pipeline and not being prepared, as well as unstable liquid levels and the introduction of air during premature emulsification. Summary of the Invention

[0010] The purpose of this invention is to provide an automated preparation machine for gas-containing microsphere injection solutions, so as to overcome the defects of the existing technology.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0012] An automated preparation machine for gas-containing microsphere injection includes a frame, a clean laminar flow system, an ultrasonic container support, a first clamp valve, a second clamp valve, a liftable ultrasonic head support, a raw material feeding system, a liquid extraction system, an air intake system, a control system, a finished product storage tank, a brine storage tank, and a waste liquid storage tank.

[0013] The frame is equipped with a main unit workbench. The clean laminar flow system is located above the frame. The ultrasonic container support is located in the middle of the main unit workbench. An ultrasonic container is mounted on the ultrasonic container support. The lower end of the ultrasonic container is connected to a silicone tube. The lower end of the silicone tube is connected to the upper end of a tee. One end of the tee is connected to the air inlet system via a No. 2 clamp valve, and the other end of the tee is connected to the liquid extraction system. A No. 1 clamp valve is installed on the ultrasonic container support. The No. 1 clamp valve is used to control the connection between the silicone tube and the tee. The No. 2 clamp valve is installed on the right side of the main unit workbench. The ultrasonic head support is mounted on the main machine workbench behind the ultrasonic container support. The ultrasonic head support is equipped with an ultrasonic head and a temperature probe. The raw material feeding system is mounted on the left side of the main machine workbench. The outlet of the raw material feeding system is connected to the ultrasonic container. The liquid extraction system is mounted on the left side of the main machine workbench and located below the raw material feeding system. The air intake system is mounted on the side of the frame. The control system is connected to the raw material feeding system, the liquid extraction system, and the air intake system. The finished product storage tank and the brine storage tank are both located on the main machine workbench. The waste liquid storage tank is located at the lower end of the frame.

[0014] The automatic preparation process is as follows: After the raw material feeding system is completed, the external ultrasonic instrument is started to heat the raw material in the ultrasonic container. When the raw material is heated to the first set temperature, the ultrasonication is stopped. The air intake system introduces inert gas at a set flow rate and maintains it for a first set time. The ultrasonic head support is raised so that the ultrasonic head is inserted below the liquid surface. The ultrasonic instrument is started to conduct ultrasonication. The air intake system continues to introduce inert gas at a set flow rate and maintains it for a second set time. Ultrasonication continues until the second set temperature is reached and then the ultrasonication is terminated. The liquid extraction system extracts the prepared microsphere injection solution to the finished product storage tank.

[0015] The automatic cleaning process is as follows: the raw material feeding system starts high-speed brine injection to spray the ultrasonic container, ultrasonic head, and temperature probe. At the same time, the liquid extraction system extracts the spray waste liquid and maintains it for a third set time. After the spraying is completed, the ultrasonic container is filled with brine and the ultrasonic process is started and maintained for a fourth set time. The liquid extraction system extracts the ultrasonic cleaning waste liquid and sprays it for cleaning again. Finally, the residual water in the ultrasonic container and pipeline is emptied to complete the cleaning.

[0016] Furthermore, the ultrasonic container support includes a fixing plate, an ultrasonic container support plate, and a silicone belt. The fixing plate is disposed on the ultrasonic container support plate, and the fixing plate is provided with two silicone belt hanging ears. The ultrasonic container is hung on the silicone belt hanging ears via the silicone belt. The lower end of the ultrasonic container is connected to a silicone tube for liquid outlet and inert gas inlet. The first clamp valve is installed on the ultrasonic container support plate and is used to clamp the silicone tube for liquid outlet and inert gas inlet of the ultrasonic container.

[0017] Furthermore, the first clamp valve includes a first clamp valve cover, a first clamp valve body, a first clamp valve core, and a first clamp valve cylinder. The silicone tube for the ultrasonic container's liquid outlet and inert gas inlet passes through the middle of the first clamp valve cover and the first clamp valve body. The first clamp valve core is laterally movable within the first clamp valve body and connected to the first clamp valve cylinder. The movement of the first clamp valve cylinder is used to flatten the silicone tube for the ultrasonic container's liquid outlet and inert gas inlet, blocking the connection between the ultrasonic container and the bottom tee.

[0018] Furthermore, the second clamp valve includes a second clamp valve cover, a second clamp valve body, a second clamp valve core, a second clamp valve cylinder, and an inert gas silicone tube. The inert gas silicone tube passes between the second clamp valve cover and the second clamp valve body. The second clamp valve core is disposed within the second clamp valve body and is perpendicular to the inert gas silicone tube. The second clamp valve cylinder is connected to the other end of the second clamp valve core. The movement of the second clamp valve cylinder is used to flatten the inert gas silicone tube and block the connection between the inert gas inlet and the bottom tee of the ultrasonic container.

[0019] Furthermore, the raw material feeding system includes a spray module, an injection pump, and a feeding peristaltic pump. The injection pump is equipped with a medical syringe for injecting human serum albumin injection solution. The feeding peristaltic pump is used for injecting sodium chloride injection solution. The spray module is mounted on the ultrasonic head support. The spray module includes a spray module body. The upper end of the spray module body is provided with a first liquid inlet and a second liquid inlet. The lower end of the spray module body is provided with two Z-shaped liquid outlet pipes. The lower ends of the Z-shaped liquid outlet pipes are located in the ultrasonic container. The first liquid inlet is connected to the injection pump, and the second liquid inlet is connected to the feeding peristaltic pump.

[0020] Furthermore, the lower end of the Z-shaped liquid outlet pipe is provided with multiple liquid spraying openings evenly distributed in a 360° pattern.

[0021] Furthermore, the ultrasonic head support includes an ultrasonic head support plate, a support rod, a flange linear bearing, and a lifting mechanism. The front end of the ultrasonic head support plate is provided with an open ring with a step, and the ultrasonic head is locked on the step of the open ring. Temperature probe mounting ports and spray module mounting ports are respectively provided on both sides of the open ring. The ultrasonic head support plate is mounted on the support rod, and the support rod passes through the main unit's worktable surface through the flange linear bearing and is connected to the lifting mechanism at the lower end of the main unit's worktable surface.

[0022] Furthermore, the lifting mechanism includes an upper fixed block, a slider, a lower fixed block, a photoelectric sensor, a fixed sliding rod, and a through-type lead screw stepper motor. The upper fixed block is fixedly connected to the lower end of the main machine's worktable. The lower fixed block is connected to the lower end of the upper fixed block via the fixed sliding rod. The slider is mounted on the fixed sliding rod. The through-type lead screw stepper motor is installed below the lower fixed block. The upper part of the slider is movably connected to a support rod passing through the upper fixed block. The lower end of the support rod is connected to the through-type lead screw stepper motor. The photoelectric sensor is mounted on the upper fixed block.

[0023] Furthermore, the liquid extraction system includes an extraction peristaltic pump, a medical three-way valve, and a medical three-way valve switching actuator. The medical three-way valve is connected to a silicone tube for inlet of the finished microsphere suspension and waste liquid, a silicone tube for outlet of waste liquid, and a silicone tube for outlet of the finished microsphere suspension. The silicone tube for inlet of the finished microsphere suspension and waste liquid is connected to the other end of the three-way valve through the extraction peristaltic pump. The medical three-way valve is connected to the medical three-way valve switching actuator.

[0024] Furthermore, the medical three-way valve switching actuator includes a valve cover, a three-way valve body fixing block, a three-way valve handle rotating block, a photoelectric sensor, and a stepper motor. The front end of the three-way valve handle rotating block has a groove that matches the handle of the medical three-way valve. The end of the three-way valve handle rotating block has a circular piece at the connection with the stepper motor and an opening for fixing the photoelectric sensor. The back of the three-way valve body fixing block has a circular recess that matches the three-way valve handle rotating block. The front of the three-way valve body fixing block has a T-shaped groove, the middle part of which is connected to the circular recess on the back. The medical three-way valve is locked in the T-shaped groove on the front of the three-way valve body fixing block. The valve cover is used to cover the medical three-way valve. The starting rotation of the stepper motor realizes the opening and closing of the medical three-way valve.

[0025] Compared with the prior art, the advantages of the present invention are as follows: The automatic preparation machine for gas-containing microsphere injection provided by the present invention greatly reduces manual operation, achieves thorough cleaning, improves the preparation effect and the stability of the liquid surface during preparation, and avoids problems such as premature emulsification introducing air. Attached Figure Description

[0026] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0027] Figure 1 This is a front view of the automatic preparation machine for gas-containing microsphere injection solution of the present invention.

[0028] Figure 2 This is a rear view of the automatic preparation machine for gas-containing microsphere injection solution of the present invention.

[0029] Figure 3 This is a structural diagram of the ultrasonic container support in this invention.

[0030] Figure 4 This is a three-dimensional view of the ultrasonic head support in this invention.

[0031] Figure 5 This is a front view of the ultrasonic head support in this invention.

[0032] Figure 6 This is a structural diagram of the No. 2 pinch valve in this invention.

[0033] Figure 7 This is a structural diagram of the spray module in this invention.

[0034] Figure 8 This is a structural diagram of the three-way valve switching actuator for traditional Chinese medicine in this invention.

[0035] In the diagram: 10 Main unit workbench, 11 Clean laminar flow system, 20 Finished product storage tank, 21 Brine storage tank, 22 Waste liquid storage tank, 30 Ultrasonic container support, 31 No. 1 clamp valve, 32 No. 2 clamp valve, 33 Ultrasonic container, 40 Ultrasonic head support, 45 Ultrasonic head, 50 Spray module, 51 Injection pump, 52 Feed peristaltic pump, 60 Extraction peristaltic pump, 61 Medical three-way valve switch actuator, 70 Temperature probe, 72 Temperature controller, 301 Fixing plate, 302 Silicone belt hook, 303 Ultrasonic container support plate, 304 Silicone belt, 311 No. 1 clamp valve cover, 312 No. 1 clamp valve body, 313 No. 1 clamp valve core, 314 No. 1 clamp valve cylinder, 331 Silicone tubing for ultrasonic container liquid outlet and inert gas inlet, 321 No. 2 clamp valve cover, 321 No. 2 clamp valve valve... Body 322, No. 2 clamp valve core 323, No. 2 clamp valve cylinder 324, inert gas silicone tube 325, ultrasonic head support plate 401, upper fixing block 402, slider 403, lower fixing block 404, photoelectric sensor 405, fixed slide rod 406, through-type lead screw stepper motor 407, support rod 408, flange linear bearing 409, first liquid inlet 501, second liquid inlet 502, spray module body 503, Z-shaped liquid outlet pipe 504, spray opening 505, valve cover 611, finished microsphere suspension and waste liquid inlet silicone tube 612, waste liquid outlet silicone tube 613, finished microsphere suspension outlet silicone tube 614, medical three-way valve 615, three-way valve body fixing block 616, three-way valve handle rotating block 617, photoelectric sensor 618, stepper motor 619. Detailed Implementation

[0036] The preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings, so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby providing a clearer and more explicit definition of the scope of protection of the present invention.

[0037] See Figure 1 and Figure 2 As shown, this embodiment discloses an automatic preparation machine for gas-containing microsphere injection liquid, including a frame, a clean laminar flow system 11, an ultrasonic container support 30, a first clamp valve 31, a second clamp valve 32, a liftable ultrasonic head support 40, a raw material feeding system, a liquid extraction system, an air intake system, a control system, a finished product storage tank 20, a brine storage tank 21, and a waste liquid storage tank 22.

[0038] The frame is equipped with a main unit workbench 10, and a clean environment monitoring probe is located below the frame. A clean laminar flow system 11 is located above the frame. An ultrasonic container support 30 is located in the middle of the main unit workbench 10. An ultrasonic container 33 is mounted on the ultrasonic container support 30. The lower end of the ultrasonic container 33 is connected to a silicone tube 331, and the lower end of the silicone tube 331 is connected to the upper end of a tee. One end of the tee is connected to the air intake system through a second clamp valve 32, and the other end of the tee is connected to the liquid extraction system. A first clamp valve 31 is installed on the ultrasonic container support 30 to control the connection between the silicone tube 331 and the tee. A second clamp valve 32 is installed on the main unit workbench 10. On the right side of the worktable 10, the ultrasonic head bracket 40 is installed on the main worktable 10 behind the ultrasonic container bracket 30. The ultrasonic head bracket 40 is equipped with an ultrasonic head 45 and a temperature probe 70. The raw material feeding system is installed on the left side of the main worktable 10. The outlet of the raw material feeding system is connected to the ultrasonic container 33. The liquid extraction system is installed on the left side of the main worktable 10 and located below the raw material feeding system. The air intake system is installed on the side of the frame. The control system is connected to the raw material feeding system, the liquid extraction system and the air intake system. The finished product storage tank 20 and the brine storage tank 21 are both located on the main worktable 10. The waste liquid storage tank 22 is located at the lower end of the frame.

[0039] The control system includes a PLC and a human-machine interface. After the control system is triggered and started by the interface, it can realize automatic preparation and automatic cleaning, and can also realize circulation. In this embodiment, the temperature is controlled by a temperature controller 72.

[0040] The automatic preparation process of this invention is as follows: After the raw material feeding system finishes feeding, the external ultrasonic instrument is started to heat the raw material in the ultrasonic container 33. When the raw material reaches the first set temperature, the ultrasonication is stopped. The air intake system introduces inert gas at a set flow rate and maintains it for a first set time. The ultrasonic head support 40 is raised so that the ultrasonic head 45 is inserted 1-3 cm below the liquid surface. The ultrasonic instrument is started to conduct ultrasonication. The air intake system continues to introduce inert gas at a set flow rate and maintains it for a second set time. Ultrasonication continues until the second set temperature is reached and then terminated. The liquid extraction system extracts the prepared microsphere injection liquid to the finished product storage tank 20. During the preparation process, if the raw material is insufficient, the inert gas pressure is too high or too low, or the temperature setting is unreasonable, the PLC will start a buzzer alarm and display text on the human-machine interface.

[0041] The automatic cleaning process of the present invention is as follows: the raw material feeding system starts high-speed brine injection to spray the ultrasonic container 33, ultrasonic head 45, and temperature probe 70. At the same time, the liquid extraction system extracts the spray waste liquid and maintains it for a third set time. After the spraying is completed, the ultrasonic container 33 is filled with brine and the ultrasonic is started and maintained for a fourth set time. The liquid extraction system extracts the ultrasonic cleaning waste liquid. The same spraying method is used to spray and clean once more. The residual water in the ultrasonic container 33 and the pipeline is then evacuated to complete the cleaning.

[0042] This invention avoids the need for a three-way valve by using a three-way valve. In addition, it adds a first clamp valve 31 and a second clamp valve 32 to cooperate with the liquid extraction system, which effectively prevents the raw materials in the ultrasonic container 33 from flowing to the three-way valve through the pipeline during ultrasonic preparation, ensuring the stability of the liquid level and allowing the raw materials to be fully ultrasonically prepared. Moreover, the entire process does not require manual intervention to open or close the valves, effectively reducing the risk of aseptic problems caused by personnel.

[0043] See Figure 3 As shown, the ultrasonic container support 30 includes a fixing plate 301, an ultrasonic container support plate 303, and a silicone belt 304. The fixing plate 301 is disposed on the ultrasonic container support plate 303. The fixing plate 301 is provided with two silicone belt hanging ears 302. The ultrasonic container 33 is hung on the silicone belt hanging ears 302 through the silicone belt 304. The lower end of the ultrasonic container 33 is connected to a silicone tube 33 for liquid outlet and inert gas inlet of the ultrasonic container. A first clamp valve 31 is installed on the ultrasonic container support plate 303 and is used to clamp the silicone tube 331 for liquid outlet and inert gas inlet of the ultrasonic container.

[0044] The first clamp valve 31 includes a first clamp valve cover 311, a first clamp valve body 312, a first clamp valve core 313, and a first clamp valve cylinder 314. The silicone tube 331 for the ultrasonic container to discharge liquid and inert gas to enter passes through the middle of the first clamp valve cover 311 and the first clamp valve body 312. There is a conical recess at the upper end of the silicone tube 331 for the ultrasonic container to discharge liquid and inert gas to enter to support the ultrasonic container 33. The first clamp valve core 313 is laterally movable inside the first clamp valve body 312 and is connected to the first clamp valve cylinder 314. The movement of the first clamp valve cylinder 314 is used to flatten the silicone tube 331 for the ultrasonic container to discharge liquid and inert gas to enter to enter to block the connection between the ultrasonic container 33 and the bottom tee.

[0045] See Figure 6 As shown, the second clamp valve 32 includes a second clamp valve cover 321, a second clamp valve body 322, a second clamp valve core 323, a second clamp valve cylinder 324, and an inert gas silicone tube 325. The inert gas silicone tube 325 passes between the second clamp valve cover 321 and the second clamp valve body 322. The second clamp valve core 323 is disposed inside the second clamp valve body 322 and is perpendicular to the inert gas silicone tube 325. The second clamp valve cylinder 324 is connected to the other end of the second clamp valve core 323. The movement of the second clamp valve cylinder 324 is used to flatten the inert gas silicone tube 325 and block the connection between the inert gas inlet and the bottom tee of the ultrasonic container 33.

[0046] See also Figure 7 As shown, the raw material feeding system includes a spray module 50, an injection pump 51, and a feeding peristaltic pump 52. The injection pump 51 is equipped with a medical syringe for injecting human serum albumin injection solution, and the feeding peristaltic pump 52 is used for injecting sodium chloride injection solution. The spray module 50 is made of 316 stainless steel and is mounted on the ultrasonic head support 40. The spray module 50 includes a spray module body 503. The upper end of the spray module body 503 is provided with a first liquid inlet 501 and a second liquid inlet 502. The lower end of the spray module body 503 is provided with two Z-shaped liquid outlet pipes 504. The lower ends of the Z-shaped liquid outlet pipes 504 are located in the ultrasonic container 33 and distributed on both sides of the ultrasonic head. The first liquid inlet 501 is connected to the injection pump 51, and the second liquid inlet 502 is connected to the feeding peristaltic pump 52.

[0047] Preferably, the Z-shaped outlet pipe 504 has a diameter of 2mm and is closed at the top. Three spray openings, each 0.2mm wide and 1.3mm deep, are located on the top side. These three openings are evenly distributed at 360 degrees, with a vertical spacing of 2mm. The two inlets and two outlet pipes of the spray module 50 are fully connected within the main body. During preparation, the spray module 50 acts as a feeding head. The injection pump is first started to inject human serum albumin into the spray module 50. Then, the feed peristaltic pump 52 starts at low speed to introduce saline solution, carrying the human serum albumin into the ultrasonic container 33. During cleaning, the spray module 50 acts as a spray head. The feed peristaltic pump 52 starts at high speed to introduce saline solution, which is sprayed out from the three openings in a fan shape, achieving 360-degree spray cleaning.

[0048] See Figure 4 and Figure 5 As shown, the ultrasonic head support 40 includes an ultrasonic head support plate 401, a support rod 408, a flange linear bearing 409, and a lifting mechanism. The front end of the ultrasonic head support plate 401 is provided with an open ring with a step. The ultrasonic head 45 is stuck on the step of the open ring. Temperature probe mounting port and spray module mounting port are respectively provided on both sides of the open ring, which are fixed by handle screws. The rear end of the ultrasonic head support plate 401 is provided with a bushing and a fixing nut, which can be connected to the support rod 408 so that the ultrasonic head, temperature probe, and spray module can all be inserted into the ultrasonic container. The ultrasonic head support plate 401 is set on the support rod 408. The support rod 408 passes through the main machine worktable 10 through the flange linear bearing 409 and is connected to the lifting mechanism at the lower end of the main machine worktable 10.

[0049] In this embodiment, the added lifting mechanism allows for controllable height and position. During ultrasonic heating, lowering the ultrasonic head by 45° effectively prevents air from being introduced into the liquid, avoiding the formation of air microspheres. Simultaneously, the deeper the ultrasonic head penetrates the liquid surface, the faster the liquid heats up, effectively reducing heating time and improving production efficiency. During ultrasonic emulsification into spheres, the ultrasonic head can be raised to a specified height according to process requirements. This height can be set via the human-machine interface, eliminating the need for manual adjustment of mechanical components and effectively reducing the risk of aseptic damage from personnel.

[0050] Specifically, the lifting mechanism includes an upper fixed block 402, a slider 403, a lower fixed block 404, a photoelectric sensor 405, a fixed sliding rod 406, and a through-type lead screw stepper motor 407. The upper fixed block 402 is fixedly connected to the lower end of the main machine worktable 10. The lower fixed block 404 is connected to the lower end of the upper fixed block 402 through the fixed sliding rod 406. The slider 403 is located on the fixed sliding rod 406. The through-type lead screw stepper motor 407 is installed below the lower fixed block 404. The upper part of the slider 403 is movably connected to a support rod 408 that passes through the upper fixed block 402. The lower end of the support rod 408 is connected to the through-type lead screw stepper motor 407. The through-type lead screw stepper motor 407 performs work to make the support rod 408 move up and down to achieve the purpose of lifting the ultrasonic head. The photoelectric sensor 405 is located on the upper fixed block 402 and achieves the purpose of lifting and positioning.

[0051] See Figure 8 As shown, the liquid extraction system includes an extraction peristaltic pump 60, a medical three-way valve 615, and a medical three-way valve switching actuator 61. The medical three-way valve 615 is connected to a finished microsphere suspension and waste liquid inlet silicone tube 612, a waste liquid outlet silicone tube 613, and a finished microsphere suspension outlet silicone tube 614. The finished microsphere suspension and waste liquid inlet silicone tube 612 is connected to the other end of the three-way valve through the extraction peristaltic pump 60. The medical three-way valve 615 is connected to the medical three-way valve switching actuator 61.

[0052] This invention replaces gravity outflow with a peristaltic pump 60, which can promptly extract spray waste liquid, ensuring cleaning effect and accelerating extraction speed to improve work efficiency. It replaces the existing method of manually selecting the flow direction of the finished microsphere suspension and waste liquid by using a medical three-way valve 615, with the medical three-way valve switch actuator 61 enabling automatic direction selection. This avoids confusion between the microsphere suspension and waste liquid caused by improper operation and effectively reduces the aseptic risk associated with manual operation.

[0053] Specifically, the medical three-way valve switching actuator 61 includes a valve cover 611, a three-way valve body fixing block 616, a three-way valve handle rotating block 617, a photoelectric sensor 618, and a stepper motor 619. The front end of the three-way valve handle rotating block 617 has a groove that matches the handle of the medical three-way valve 615. The end of the three-way valve handle rotating block 617, at the connection point with the stepper motor 619, has a circular piece (1mm thick and 60mm in diameter) and a notch (2mm wide) for fixing the photoelectric sensor 618. The notch can cooperate with the photoelectric sensor to achieve rotational positioning. The three-way valve body... The back of the fixing block 616 is provided with a circular recess that cooperates with the rotating block 617 of the three-way valve handle. The front of the fixing block 616 of the three-way valve body is provided with a T-shaped groove. The middle part of the T-shaped groove is connected to the circular recess on the back. The medical three-way valve 615 is stuck in the T-shaped groove on the front of the fixing block 616 of the three-way valve body. The valve cover 611 is used to cover the medical three-way valve 615. The starting rotation of the stepper motor 619 realizes the opening and closing of the medical three-way valve 615. The medical three-way valve switching actuator 61 is suitable for the direction selection of the medical three-way valve, selectively diverting the finished microsphere suspension and waste liquid to the corresponding storage tank.

[0054] In this embodiment, the control system uses a Mitsubishi FX5U-64MT PLC and a Mitsubishi GS2110 human-machine interface to control the equipment, realize automatic feeding, preparation, finished product extraction, cleaning and other processes, and realize cyclic operation without human intervention. The PLC has 5 axes of motion, which respectively control the rotation of an injection pump 51, two peristaltic pumps (feeding peristaltic pump 52 and extraction peristaltic pump 60), a medical three-way valve 615, and the lifting and lowering of an ultrasonic head support 40.

[0055] This embodiment features 485 communication functionality, used to read the temperature measured by the temperature controller 72 (Omron E5CC temperature controller) during the preparation process, enabling temperature-based control of the preparation process. This embodiment also includes analog output functionality, allowing control of the ultrasonic instrument's output power during preparation via analog signals.

[0056] Although embodiments of the present invention have been described in conjunction with the accompanying drawings, the patent owner may make various modifications or alterations within the scope of the appended claims, as long as they do not exceed the protection scope described in the claims of the present invention, they shall be within the protection scope of the present invention.

Claims

1. An automated preparation machine for gas-containing microsphere injection solutions, characterized in that, It includes a frame, a clean laminar flow system, an ultrasonic container support, a No. 1 clamp valve, a No. 2 clamp valve, a liftable ultrasonic head support, a raw material feeding system, a liquid extraction system, an air intake system, a control system, a finished product storage tank, a brine storage tank, and a waste liquid storage tank. The frame is equipped with a main unit workbench. The clean laminar flow system is located above the frame. The ultrasonic container support is located in the middle of the main unit workbench. An ultrasonic container is mounted on the ultrasonic container support. The lower end of the ultrasonic container is connected to a silicone tube. The lower end of the silicone tube is connected to the upper end of a tee. One end of the tee is connected to the air inlet system via a No. 2 clamp valve, and the other end of the tee is connected to the liquid extraction system. A No. 1 clamp valve is installed on the ultrasonic container support. The No. 1 clamp valve is used to control the connection between the silicone tube and the tee. The No. 2 clamp valve is installed on the right side of the main unit workbench. The ultrasonic head support is mounted on the main machine workbench behind the ultrasonic container support. The ultrasonic head support is equipped with an ultrasonic head and a temperature probe. The raw material feeding system is mounted on the left side of the main machine workbench. The outlet of the raw material feeding system is connected to the ultrasonic container. The liquid extraction system is mounted on the left side of the main machine workbench and located below the raw material feeding system. The air intake system is mounted on the side of the frame. The control system is connected to the raw material feeding system, the liquid extraction system, and the air intake system. The finished product storage tank and the brine storage tank are both located on the main machine workbench. The waste liquid storage tank is located at the lower end of the frame. The automatic preparation process is as follows: After the raw material feeding system is completed, the external ultrasonic instrument is started to heat the raw material in the ultrasonic container. When the raw material is heated to the first set temperature, the ultrasonication is stopped. The air intake system introduces inert gas at a set flow rate and maintains it for a first set time. The ultrasonic head support is raised so that the ultrasonic head is inserted below the liquid surface. The ultrasonic instrument is started to conduct ultrasonication. The air intake system continues to introduce inert gas at a set flow rate and maintains it for a second set time. Ultrasonication continues until the second set temperature is reached and then the ultrasonication is terminated. The liquid extraction system extracts the prepared microsphere injection solution to the finished product storage tank. The automatic cleaning process is as follows: the raw material feeding system starts high-speed brine injection to spray the ultrasonic container, ultrasonic head, and temperature probe. At the same time, the liquid extraction system extracts the spray waste liquid and maintains it for a third set time. After the spraying is completed, the ultrasonic container is filled with brine and the ultrasonic process is started and maintained for a fourth set time. The liquid extraction system extracts the ultrasonic cleaning waste liquid and sprays it for cleaning again. Finally, the residual water in the ultrasonic container and pipeline is emptied to complete the cleaning.

2. The automated preparation machine for gas-containing microsphere injection solution according to claim 1, characterized in that, The ultrasonic container support includes a fixing plate, an ultrasonic container support plate, and a silicone belt. The fixing plate is disposed on the ultrasonic container support plate, and the fixing plate is provided with two silicone belt hanging ears. The ultrasonic container is hung on the silicone belt hanging ears via the silicone belt. The lower end of the ultrasonic container is connected to a silicone tube for liquid outlet and inert gas inlet. The first clamp valve is installed on the ultrasonic container support plate and is used to clamp the silicone tube for liquid outlet and inert gas inlet of the ultrasonic container.

3. The automated preparation machine for gas-containing microsphere injection solution according to claim 2, characterized in that, The first clamp valve includes a first clamp valve cover, a first clamp valve body, a first clamp valve core, and a first clamp valve cylinder. The silicone tube for the ultrasonic container's liquid outlet and inert gas inlet passes through the middle of the first clamp valve cover and the first clamp valve body. The first clamp valve core is laterally movable within the first clamp valve body and connected to the first clamp valve cylinder. The movement of the first clamp valve cylinder is used to flatten the silicone tube for the ultrasonic container's liquid outlet and inert gas inlet, blocking the connection between the ultrasonic container and the bottom tee.

4. The automated preparation machine for gas-containing microsphere injection solution according to claim 1, characterized in that, The second clamp valve includes a second clamp valve cover, a second clamp valve body, a second clamp valve core, a second clamp valve cylinder, and an inert gas silicone tube. The inert gas silicone tube passes between the second clamp valve cover and the second clamp valve body. The second clamp valve core is located inside the second clamp valve body and is perpendicular to the inert gas silicone tube. The second clamp valve cylinder is connected to the other end of the second clamp valve core. The movement of the second clamp valve cylinder is used to flatten the inert gas silicone tube and block the connection between the inert gas inlet and the T-junction at the bottom of the ultrasonic container.

5. The automated preparation machine for gas-containing microsphere injection solution according to claim 1, characterized in that, The raw material feeding system includes a spray module, an injection pump, and a feeding peristaltic pump. The injection pump is equipped with a medical syringe for injecting human serum albumin injection solution. The feeding peristaltic pump is used for injecting sodium chloride injection solution. The spray module is mounted on the ultrasonic head support and includes a spray module body. The upper end of the spray module body is provided with a first liquid inlet and a second liquid inlet. The lower end of the spray module body is provided with two Z-shaped liquid outlet tubes. The lower ends of the Z-shaped liquid outlet tubes are located in the ultrasonic container. The first liquid inlet is connected to the injection pump, and the second liquid inlet is connected to the feeding peristaltic pump.

6. The automated preparation machine for gas-containing microsphere injection solution according to claim 5, characterized in that, The lower end of the Z-shaped liquid outlet pipe is provided with multiple liquid spray openings evenly distributed in a 360° pattern.

7. The automated preparation machine for gas-containing microsphere injection solution according to claim 1, characterized in that, The ultrasonic head support includes an ultrasonic head support plate, a support rod, a flange linear bearing, and a lifting mechanism. The front end of the ultrasonic head support plate is provided with an open ring with a step. The ultrasonic head is locked on the step of the open ring. Temperature probe mounting ports and spray module mounting ports are respectively provided on both sides of the open ring. The ultrasonic head support plate is mounted on the support rod. The support rod passes through the main unit's worktable through the flange linear bearing and is connected to the lifting mechanism at the lower end of the main unit's worktable.

8. The automated preparation machine for gas-containing microsphere injection solution according to claim 7, characterized in that, The lifting mechanism includes an upper fixed block, a slider, a lower fixed block, a photoelectric sensor, a fixed sliding rod, and a through-type lead screw stepper motor. The upper fixed block is fixedly connected to the lower end of the main machine's worktable. The lower fixed block is connected to the lower end of the upper fixed block via the fixed sliding rod. The slider is mounted on the fixed sliding rod. The through-type lead screw stepper motor is installed below the lower fixed block. The upper part of the slider is movably connected to a support rod passing through the upper fixed block. The lower end of the support rod is connected to the through-type lead screw stepper motor. The photoelectric sensor is mounted on the upper fixed block.

9. The automated preparation machine for gas-containing microsphere injection solution according to claim 1, characterized in that, The liquid extraction system includes an extraction peristaltic pump, a medical three-way valve, and a medical three-way valve switching actuator. The medical three-way valve is connected to a silicone tube for inlet of finished microsphere suspension and waste liquid, a silicone tube for outlet of waste liquid, and a silicone tube for outlet of finished microsphere suspension. The silicone tube for inlet of finished microsphere suspension and waste liquid is connected to the other end of the three-way valve through the extraction peristaltic pump. The medical three-way valve is connected to the medical three-way valve switching actuator.

10. The automated preparation machine for gas-containing microsphere injection solution according to claim 9, characterized in that, The medical three-way valve switching mechanism includes a valve cover, a three-way valve body fixing block, a three-way valve handle rotating block, a photoelectric sensor, and a stepper motor. The front end of the three-way valve handle rotating block has a groove that matches the handle of the medical three-way valve. The end of the three-way valve handle rotating block has a circular piece at the connection with the stepper motor and an opening for fixing the photoelectric sensor. The back of the three-way valve body fixing block has a circular recess that matches the three-way valve handle rotating block. The front of the three-way valve body fixing block has a T-shaped groove, the middle part of which is connected to the circular recess on the back. The medical three-way valve is locked in the T-shaped groove on the front of the three-way valve body fixing block. The valve cover is used to cover the medical three-way valve. The starting rotation of the stepper motor realizes the opening and closing of the medical three-way valve.

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