Microsphere release test system

Abstract

The utility model discloses a microsphere release test system which comprises a microsphere release instrument host, an injection sampling pump, a sample collector and a liquid supplementing storage station, and the microsphere release instrument host comprises a rack shell, a water tank, a sealed sample tube, a stirring driving device, a temperature control device and a water level control device. In the testing process of the testing system, all sealed samples are placed in a temperature-controllable water bath, sampling is automatically carried out according to a set time interval and temperature, a culture agent is automatically replaced after the samples are taken out, automation and standardization are achieved, the requirement for microsphere release rate detection is met, the testing and sampling efficiency is improved, and the testing cost is reduced. And the labor cost is reduced.

Description

Technical Field

[0001] This invention belongs to the field of drug dissolution testing technology, specifically relating to a testing system for microsphere release. Background Technology

[0002] Microspheres are tiny spherical entities formed by dissolving or dispersing drugs in a polymer matrix, such as risperidone microspheres and leuprorelin acetate microspheres. As long-acting sustained-release formulations, microspheres are administered subcutaneously or intramuscularly, allowing the drug to be slowly released over a certain period of time, maintaining an effective blood drug concentration in the body for a long time, avoiding peak and trough phenomena in blood drug concentration, reducing toxic side effects, significantly reducing the frequency of dosing, and improving patient compliance. Therefore, they have gradually become a popular research topic in modern pharmaceutics.

[0003] Microsphere release rate detection is a crucial aspect of the entire drug development process and a key indicator for drug evaluation and quality control. However, the development of in vitro release methods for microspheres is limited due to factors such as the lack of standardized in vitro release rate guidance methods and mature in vivo-in vitro correlation models. Researchers generally employ self-designed methods to simulate in vivo release conditions as closely as possible to predict the release behavior of microspheres in vivo.

[0004] Currently, commonly used methods for measuring the in vitro release rate of microspheres include the flow cell method, dialysis method, and shake flask method.

[0005] The flow-through cell method, included in the USP, EP, and JP pharmacopoeias, is a novel dissolution method specifically designed for poorly soluble and sustained-release drug formulations. However, due to the high cost, low throughput, and relatively cumbersome operation of the instrument, its adoption rate in microsphere quality control is low.

[0006] Dialysis involves placing drug microspheres into a dialysis bag and then testing them in a suitable medium. This method avoids microsphere loss during sampling. However, the dialysis membrane may hinder drug diffusion, limiting drug release. Furthermore, if the released drug cannot immediately pass through the dialysis bag, the free drug within the bag may not meet the leakage conditions, further affecting the microsphere release rate.

[0007] The shake-flask method is a commonly used method for determining the in vitro release rate of microspheres. A certain amount of microspheres is directly placed into a certain volume of medium and shaken at a specific frequency, or allowed to stand (shaking to homogenize the solution before sampling). Samples are taken at regular intervals, with fresh medium added simultaneously. This method has the advantages of high throughput and low cost. However, due to the lack of standardized equipment, the size or shape of the bottles / centrifuge tubes used, the height of the sampling position, etc., can all affect the release results. Furthermore, because the in vitro release time of microspheres is relatively long, manual sampling at regular intervals over extended periods is required, increasing labor costs. Utility Model Content

[0008] To address the aforementioned problems, this invention discloses a microsphere release testing system. Based on existing technologies, this invention designs and manufactures an automated, standardized, and universally applicable device using the shake-flask method. Within a controllable temperature range and at a controllable stirring speed, microsphere products are released and sampled in 24 sealed sample cells, solving the problem that existing testing systems are unsuitable for detecting microsphere release rates.

[0009] The specific technical solution is as follows:

[0010] A microsphere release testing system includes a microsphere release instrument main unit, an injection sampling pump, a sample collector, and a replenishment and storage station. The microsphere release instrument main unit includes a frame housing, a water tank, sealed sample tubes, a stirring drive device, a temperature control device, and a water level control device. The water tank is located in the middle of the frame housing. The temperature control device is used to heat the water in the water tank. The water level control device is used to replenish the water in the water tank. A removable and replaceable tube sheet is horizontally installed at the upper end of the frame housing. The tube sheet has several holes for installing sealed sample tubes. An anti-floating device is installed at the bottom of the tube sheet at each hole to prevent the sealed sample tubes from floating in the water tank. The lower end of the sealed sample tube is embedded into the hole and enters the water tank. The sealed sample tube is fully enclosed. Each sealed sample tube contains a stir bar, which is driven to rotate by a stirring drive device located at the lower end of the frame housing. The upper end of each sealed sample tube is equipped with a removable sealing cap, which includes an injection port, a sampling port, an air inlet, a liquid replenishment port, and a temperature probe insertion port. The sampling port and liquid replenishment port are used to embed a sampling needle and a liquid replenishment needle, respectively. One end of each needle is connected to an injection sampling pump via tubing. The injection sampling pump is connected to a sample collector and a liquid replenishment storage station via tubing. The injection sampling pump extracts a sample from the sealed sample tube using the sampling needle and delivers the sample to the sample collector, thus achieving sampling. A movable injection sampling pump draws liquid from the liquid replenishment storage station and injects it into the sample collector via the liquid replenishment needle, thus achieving liquid replenishment.

[0011] Furthermore, the temperature control device includes an outer casing, a circulating pump, a heating element, a temperature measuring probe, an inlet pipe, and an outlet pipe. The outer casing is located at the rear end of the frame housing. The circulating pump and the heating element are housed within the casing. The inlet end of the circulating pump is connected to the bottom of the water tank via the inlet pipe, and the outlet end of the circulating pump is connected to the heating element via a pipe. One end of the heating element is connected to the side wall of the water tank via the outlet pipe. A temperature measuring probe is installed in the heating element to monitor and control the water temperature entering the water bath.

[0012] Furthermore, the water level control device includes a mounting frame, a replenishment tank, a replenishment pipe, and a liquid level sensor. The replenishment tank is mounted on the upper rear end of the frame housing via the mounting frame. The bottom port of the replenishment tank is connected to one end of the replenishment pipe via a switch valve. The other end of the replenishment pipe passes downward through the tube sheet and enters the water tank. A liquid level sensor is installed on the inner wall of the water tank to detect the water level.

[0013] Furthermore, an insulation cover is hinged to the upper end of the frame housing, and the insulation cover is placed on the tube sheet, so that a closed heat chamber is formed between the inner side of the insulation cover and the upper end of the tube sheet.

[0014] Furthermore, each of the anti-floating devices includes fasteners and O-rings. The number of fasteners is several and they are evenly distributed on the outside of the tube hole. The O-rings are fitted on the outside of the fasteners, making the O-rings polygonal in shape. The sides of the O-rings extend to the bottom of the tube hole and fit the O-rings against the outer wall of the sealed sample tube to achieve positioning.

[0015] Furthermore, the tube sheet is placed on the upper end of the frame housing, and handles are provided on both sides of the upper end of the tube sheet. Several positioning grooves are opened at one end of the tube sheet. The positioning grooves cooperate with the positioning posts set at one end of the top of the frame housing to achieve horizontal positioning of the tube sheet.

[0016] Furthermore, there are several stirring drive devices, each mounted on a mounting plate at the bottom of the frame housing. Each stirring drive device corresponds to the position of a sealed sample tube. The stirring drive device includes a stirring motor, a connecting seat on the output end of the stirring motor, and magnets on both sides of the upper end of the connecting seat. The magnets are close to the bottom of the water tank, and the stirring motor drives the two magnets to rotate, thereby driving the stir bar in the sealed sample tube to rotate.

[0017] Furthermore, the bottom of the sealing cap is provided with a sealing part for embedding into the upper opening of the sealing sample tube, and a sealing ring is sleeved on the outside of the sealing part, so that the sealing part achieves sealing by pressing against the inner wall of the sealing sample tube through the sealing ring.

[0018] Furthermore, the injection sampling pump integrates a control system, which includes a PLC controller and a touch screen. The PLC controller is electrically connected to the touch screen, the stirring drive device, the temperature control device, the water level control device, the injection sampling pump, and the temperature probe socket.

[0019] The test method for the microsphere release test system specifically includes the following steps:

[0020] S1. Preparation: First, heat the water in the tank to a constant temperature using a temperature control device. Then, insert the sealed sample tubes one by one into the tube holes of the tube sheet. Add solvent and stir bar to each sealed sample tube. Weigh a quantitative amount of microspheres and inject them into the sealed sample tubes. Then, cover the sealed cap and place the sampling needle and replenishment needle into the sampling hole and replenishment hole, respectively. Finally, close the heat preservation cap.

[0021] S2. Stirring: The test system is controlled via a touch screen. The stirring drive device drives the stir bar in each sealed sample tube to rotate and stir.

[0022] S3. Sampling: When the sampling time point is reached, sampling begins after the stir bar has stopped stirring for a period of time. The injection sampling pump extracts the mixed solution in the sealed sample tube through the sampling needle and delivers it to the sample collector to complete the sampling.

[0023] S4. After replenishment and sampling are completed, the injection sampling pump extracts the solvent from the replenishment storage station through the pipeline and delivers it to the sealed sample tube to complete the replenishment. Then, steps S3 and S4 are repeated.

[0024] S5. Cleaning and Testing: After the test is completed, clean the sealed sample tube, sealing cap, and injection sampling pump tubing.

[0025] The beneficial effects of this invention are reflected in:

[0026] During the testing process of the testing system of this invention, all sealed samples are placed in a water bath with a controllable temperature. Sampling is automatically performed at set time intervals and temperatures. After the samples are taken out, the culture medium is automatically replaced, realizing automation and standardization, meeting the requirements of microsphere release detection, improving testing and sampling efficiency, and reducing labor costs.

[0027] The microsphere release apparatus of this invention meets the testing needs of different types of microsphere products. It adopts online water circulation heating to accurately control the water temperature and is equipped with an automatic water replenishment device to prevent the liquid level in the water tank from dropping due to evaporation, thus ensuring the quality of the test. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the structure of the present invention.

[0029] Figure 2 This is a perspective view of the microsphere release device main unit after the insulation cover has been removed.

[0030] Figure 3 This is a top view of the microsphere release device main unit after the insulation cover has been removed.

[0031] Figure 4 This is a schematic diagram of the tube sheet structure in this invention.

[0032] Figure 5 This is a schematic diagram of the anti-floating device in this invention.

[0033] Figure 6 This is a cross-sectional view of the sealed sample tube and the stirring drive device in this invention.

[0034] Figure 7 This is a schematic diagram of the sealing cap structure in this invention.

[0035] Figure 8 This is a schematic diagram of the temperature control device in this invention.

[0036] Figure 9 This is a schematic diagram of the water level control device in this invention.

[0037] Explanation of reference numerals in the attached figures: 1. Microsphere release device main unit; 2. Injection sampling pump; 21. Touch screen display; 3. Sample collector; 4. Frame housing; 41. Insulation cover;

[0038] 5. Water tank; 51. Tube plate; 52. Pipe hole; 53. Fastener; 54. O-ring; 55. Handle; 56. Positioning groove;

[0039] 6. Sealed sample tube, 61. Sealing cap, 62. Sealing part, 63. Sealing ring, 64. Injection hole, 65. Sampling hole, 66. Air inlet, 67. Liquid replenishment hole, 68. Temperature probe insertion hole;

[0040] 7. Stirring drive device; 71. Mounting plate; 72. Stirring motor; 73. Connecting seat; 74. Magnet; 75. Stirring element;

[0041] Temperature control device 8, outer casing 81, circulating pump 82, heating element 83, temperature measuring probe 84, water inlet pipe 85, water outlet pipe 86;

[0042] Water level control device 9, mounting bracket 91, replenishment tank 92, switch valve 93, replenishment pipe 94. Detailed Implementation

[0043] To make the technical solution of this invention clearer and more explicit, the invention will be further described below with reference to the accompanying drawings. Any solution derived by equivalent substitution and conventional reasoning of the technical features of this invention falls within the protection scope of this invention. The fixed connections and fixed installations mentioned in this invention are all common connection methods in the mechanical field, including welding, bolt and nut connections, and screw connections.

[0044] In the description of this invention, it should be understood that the terms "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0045] Please see Figure 1-9 This embodiment provides a microsphere release testing system that enables the testing of microsphere release under specified conditions. Microsphere products are released and sampled in 24 sealed sample tubes 6 within a controlled temperature range and at a controlled stirring speed. During the test, all sealed samples are placed in a water bath at a controlled temperature, and sampling is performed at set time intervals and temperatures. The culture medium is replaced after each sample is removed, and the system is equipped with an automatic water replenishment device to prevent the liquid level in the water tank 5 from dropping due to evaporation.

[0046] The testing system includes a microsphere release device 1, an injection sampling pump 2, a sample collector 3, and a replenishment storage station. The microsphere release device 1 includes a frame housing 4, a water tank 5, sealed sample tubes 6, a stirring drive device 7, a temperature control device 8, and a water level control device 9. The water tank 5 is located in the middle of the frame housing 4. The temperature control device 8 is used to heat the water in the water tank. The water level control device 9 is used to replenish the water in the water tank. A tube plate 51 is horizontally provided at the upper end of the frame housing 4. In this embodiment, the tube plate has 24 tube holes 52 for installing sealed sample tubes 6, so that the tube plate 51 can accommodate up to 24 sealed sample tubes 6. An anti-floating device is provided at the bottom of the tube plate at each tube hole 52 to prevent the sealed sample tubes 6 from floating in the water tank and to play a positioning role.

[0047] The lower end of the sealed sample tube 6 is embedded into the tube hole 52 and enters the water tank 5. The bottom end of the sealed sample tube 6 is supported at the bottom end of the water tank 5. Before loading the microsphere sample, a stir bar 75 is installed in each sealed sample tube 6. The stir bar 75 in each sealed sample tube 6 is driven to rotate by a stirring drive device 7 located at the lower end of the frame housing 4. The upper end of the sealed sample tube 6 is provided with a removable sealing cap 61. The bottom of the sealing cap 61 is provided with a sealing part 62 for embedding into the upper opening of the sealed sample tube 6. A sealing ring 63 is sleeved on the outside of the sealing part, so that the sealing part is sealed by the sealing ring 63 pressing against the inner wall of the sealed sample tube 6 to prevent evaporation. The sealing cap 61 is provided with an injection hole 64, a sampling hole 65, an air inlet 66 with a one-way valve, a liquid replenishment hole 67, and an insertion hole 68 for installing a temperature probe. The sampling hole 65 and the liquid replenishment hole 67 are respectively used to embed a sampling needle and a liquid replenishment needle. One end of each needle is connected to an injection sampling pump 2 via tubing. The injection sampling pump 2 is connected to a sample collector 3 and a liquid replenishment storage station via tubing. The injection sampling pump 2 extracts a sample from the sealed sample tube 6 through the sampling needle and delivers the sample to the sample collector 3, thus achieving sampling. The sample collector 3 collects samples at each sampling time. The sample delivery head moves the needle to the rinsing position to clean the needle, and then moves it to the collection position. The sampling pump delivers the sample into the sample vial. The movable injection sampling pump 2 draws liquid from the liquid replenishment storage station and injects it into the sample collector 3 through the liquid replenishment needle, thus achieving liquid replenishment.

[0048] In this embodiment, the temperature control device 8 includes a housing 81, a circulating pump 82, a heating element 83, a temperature measuring probe 84, a water inlet pipe 85, and a water outlet pipe 86. The housing 81 is located at the rear end of the frame housing 4. The circulating pump 82 and the heating element 83 are installed in the housing. The water inlet of the circulating pump 82 is connected to the bottom of the water tank 5 through the water inlet pipe 85, and the water outlet of the circulating pump 82 is connected to the heating element 83 through a pipe. One end of the heating element 83 is connected to the side wall of the water tank 5 through the water outlet pipe 86. The temperature measuring probe 84 is installed in the heating element 83. The temperature measuring probe 84 is used to monitor and control the water temperature entering the water bath. This heating system is an online water circulation heating system. The temperature measuring probe 84 is installed in the heating element 83 to control the water temperature entering the water bath. This design is different from other designs that directly install heaters in the water bath.

[0049] Because the microsphere release cycle is relatively long, the reaction rate can be increased by raising the temperature during the experiment. Therefore, the system can operate from room temperature to 70 degrees Celsius. However, high temperatures can cause water evaporation, and once the water level in tank 5 drops, it becomes difficult to maintain the medium in the sealed sample tube 6 at the set temperature. To address this issue, a water level control device 9 for tank 5 was designed: an additional replenishment tank 92 is installed above tank 5. When the liquid level in tank 5 drops, water is automatically injected into tank 5. The water level control device 9 specifically includes a mounting bracket 91, a replenishment tank 92, a replenishment pipe 94, and a liquid level sensor (not shown in the figure). The replenishment tank 92 is mounted on the outer shell 81 at the rear end of the frame housing 4 via the mounting bracket 91. The bottom port of the replenishment tank 92 is connected to one end of the replenishment pipe 94 via a switch valve 93. The other end of the replenishment pipe 94 passes downward through the tube sheet 51 and enters the water tank. A liquid level sensor is installed on the inner wall of the water tank to detect the water level. When the water level is lower than the set value, the control system controls the switch valve 93 to open and inject water into tank 5.

[0050] The upper end of the frame housing 4 is hinged with an insulation cover 41, which covers the tube sheet 51 and forms a closed heat chamber between the inner side of the insulation cover 41 and the upper end of the tube sheet 51. In order to maintain a stable water temperature, the heat chamber on the water tank 5 separates the hot water tank 5 from the air and reduces water evaporation.

[0051] In this embodiment, the anti-floating device includes fasteners 53 and O-rings 54. There are three fasteners 53, which are evenly distributed around the outer periphery of the tube hole 52. The O-rings 54 are sleeved on the outside of the three fasteners 53. The O-rings 54 are elastic and are equilateral triangular in shape. The side of the O-rings 54 extends to the bottom of the tube hole 52 and fits against the outer wall of the sealed sample tube 6. The tension of the O-rings 54 is used to achieve positioning to prevent the sealed sample tube 6 from floating in the water tank 5 under the buoyancy of the water.

[0052] Since different types of microsphere products need to be tested in glass tubes of different capacities, the tube sheet 51 is detachable and replaceable. The tube holes 52 on different tube sheets 51 are of different sizes to accommodate sealed sample tubes 6 of different capacities. The tube sheet 51 is placed on the upper end of the frame housing 4, or it can be fixed to the frame housing 4 by fasteners 53. Handles 55 are provided on both sides of the upper end of the tube sheet 51, and several positioning grooves 56 are opened at one end of the tube sheet 51. The positioning grooves 56 cooperate with the positioning posts set at one end of the top of the frame housing 4 to achieve horizontal positioning of the tube sheet 51. During operation, the tube sheet 51 located on the water tank 5 can be easily replaced by simply lifting the two handles 55.

[0053] There are 24 stirring drive devices 7, which are respectively set on the mounting plate 71 at the bottom of the frame housing 4. Each stirring drive device 7 corresponds to the position of a sealed sample tube 6. The stirring drive device 7 includes a stirring motor 72, a connecting seat 73 set on the output end of the stirring motor 72, and magnets 74 set on both sides of the upper end of the connecting seat 73. In this embodiment, the stirring motor 72 is a speed-controlled motor, which can control the stirring speed from 0 to 1000 revolutions per minute. The magnets 74 are set close to the bottom of the water tank 5, and the stirring motor 72 drives the two magnets 74 to rotate, thereby driving the stir bar 75 in the sealed sample tube 6 to rotate for stirring.

[0054] In this embodiment, the injection sampling pump 2 includes four injection pumps, each with a drive motor, and each motor drives six syringes. The system has four injection pumps, which can drive 24 syringes to inject samples and replenishment fluid into 24 glass tubes. Each syringe has a four-way valve, one of which is connected to the syringe, and the other three are used for pulling in samples, delivering samples to the collector, and replacing replenishment fluid, respectively. Depending on different needs, one to four injection pumps can be installed. The specific structure and usage of the injection sampling pump 2 and sample collector 3 used in this invention have been disclosed in patent number: CN202010907775.2, and are prior art, so they will not be described in detail here.

[0055] The injection sampling pump 2 integrates a control system to control the operation of all equipment. The control system includes a PLC controller and a touch screen 21. The touch screen 21 is located at the front end of the injection sampling pump 2 and is used to display the control program and user interface. The PLC controller is electrically connected to the touch screen 21, the stirring drive device 7, the temperature control device 8, the water level control device 9, the injection sampling pump 2, and the temperature probe socket 68.

[0056] This embodiment also discloses a testing method for a microsphere release testing system, which specifically includes the following steps:

[0057] First, the water in the water tank 5 is heated to a constant temperature range of room temperature to 70°C using the temperature control device 8. Then, the sealed sample tubes 6 are inserted one by one into the tube holes 52 of the tube sheet 51. A solvent and a stir bar 75 are added to each sealed sample tube 6. A quantitative amount of microspheres is weighed and injected into the sealed sample tube 6. Then, the sealing cap 61 is closed and the sampling needle and the replenishment needle are placed into the sampling hole 65 and the replenishment hole 67. Finally, the heat preservation cap 41 is closed.

[0058] The stirring and testing system is controlled via the touch screen 21. The stirring drive 7 drives the stir bar 75 in each sealed sample tube 6 to rotate and stir.

[0059] Sampling: Due to the extremely small size of the microspheres, once the drug is released from them, it cannot be observed with the naked eye. In most cases, the drug sample and microspheres are mixed in a solution. In order to sample from such a mixed solution, the procedure must stop stirring for a period of time before sampling. When the sampling time point is reached, sampling begins after the stir bar 75 has stopped stirring for a period of time. The injection sampling pump 2 draws the mixed solution from the sealed sample tube 6 through the sampling needle and delivers it to the sample collector 3, thus completing the sampling.

[0060] After replenishment and sampling are completed, the injection sampling pump 2 extracts the solvent from the replenishment storage station through the pipeline and delivers it to the sealed sample tube 6 to complete the replenishment. The stirring and sampling steps are repeated according to the set time interval and temperature.

[0061] After cleaning and testing, clean the sealed sample tube 6, the sealed cap 61, and the tubing of the injection sampling pump 2.

[0062] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A microsphere release testing system, characterized in that, The device includes a microsphere release instrument main unit (1), an injection sampling pump (2), a sample collector (3), and a replenishment storage station. The microsphere release instrument main unit (1) includes a frame housing (4), a water tank (5), a sealed sample tube (6), a stirring drive device (7), a temperature control device (8), and a water level control device (9). The water tank (5) is located in the middle of the frame housing. The temperature control device (8) is used to heat the water in the water tank. The water level control device (9) is used to replenish the water in the water tank. The upper end of the frame housing (4) is horizontally provided with a removable and replaceable tube plate (51). The tube plate (51) has several tube holes (52) for installing the sealed sample tube. The bottom of the tube plate is provided with an anti-floating device at each tube hole (52) to prevent the sealed sample tube (6) from floating in the water tank. The lower end of the sealed sample tube (6) is embedded into the tube hole (52) and enters the water tank. A stir bar (75) is placed inside the sealed sample tube (6). Each sealed sample tube (6) has a stir bar (75) driven to rotate by a stirring drive device (7) located at the lower end of the frame housing (4). The upper end of the sealed sample tube (6) is provided with a removable sealing cap (61). The sealing cap (61) is provided with an injection hole (64), a sampling hole (65), an air inlet (66), a liquid replenishment hole (67), and a temperature probe insertion hole (68). The sampling hole (65) and the liquid replenishment hole (67) are respectively used for embedding The sampling needle and the replenishment needle are connected at one end to the injection sampling pump (2) through a pipeline. The injection sampling pump (2) is connected to the sample collector (3) and the replenishment storage station through a pipeline. The injection sampling pump (2) takes a sample from the sealed sample tube (6) through the sampling needle and delivers the sample to the sample collector (3) to realize sampling. The movable injection sampling pump (2) draws replenishment through the replenishment storage station and injects it into the sample collector (3) through the replenishment needle to realize replenishment.

2. The microsphere release testing system as described in claim 1, characterized in that, The temperature control device (8) includes an outer shell (81), a circulating pump (82), a heating tube (83), a temperature measuring probe (84), a water inlet pipe (85), and a water outlet pipe (86). The outer shell (81) is located at the rear end of the frame housing (4). The circulating pump (82) and the heating tube (83) are installed in the outer shell. The water inlet end of the circulating pump (82) is connected to the bottom of the water tank through the water inlet pipe. The water outlet end of the circulating pump (82) is connected to the heating tube (83) through a pipeline. One end of the heating tube (83) is connected to the side wall of the water tank (5) through the water outlet pipe (86). The temperature measuring probe (84) is installed in the heating tube (83). The temperature measuring probe (84) is used to monitor and control the water temperature entering the water bath.

3. The microsphere release testing system as described in claim 1, characterized in that, The water level control device (9) includes a mounting frame (91), a replenishment tank (92), a replenishment pipe (94), and a liquid level sensor. The replenishment tank (92) is mounted on the upper rear end of the frame housing (4) via the mounting frame (91). The bottom port of the replenishment tank (92) is connected to one end of the replenishment pipe (94) via a switch valve (93). The other end of the replenishment pipe (94) passes through the tube sheet (51) and enters the water tank (5). A liquid level sensor is installed on the water tank (5) to detect the water level of the water tank (5).

4. The microsphere release testing system as described in claim 1, characterized in that, Each of the anti-floating devices includes fasteners (53) and O-rings (54). There are several fasteners (53) and they are evenly distributed on the outside of the tube hole (52). The O-rings (54) are fitted on the outside of the fasteners (53) and the O-rings (54) are polygonal in shape. The side of the O-rings (54) extends to the bottom of the tube hole (52) and the O-rings (54) fits against the outer wall of the sealed sample tube (6) to achieve positioning.

5. The microsphere release testing system as described in claim 1, characterized in that, The tube sheet (51) is placed on the upper end of the frame housing (4). Handles (55) are provided on both sides of the upper end of the tube sheet (51). Several positioning grooves (56) are opened at one end of the tube sheet (51). The positioning grooves (56) cooperate with the positioning post set at one end of the top of the frame housing (4) to realize the horizontal positioning of the tube sheet (51).

6. The microsphere release testing system as described in claim 5, characterized in that, The upper end of the frame housing (4) is hinged with a heat insulation cover (41), which covers the tube sheet (51) and forms a closed heat chamber between the inner side of the heat insulation cover (41) and the upper end of the tube sheet (51).

7. The microsphere release testing system as described in claim 1, characterized in that, The number of stirring drive devices (7) is several and they are respectively set on the mounting plate (71) at the bottom of the frame housing (4). Each stirring drive device (7) corresponds to the position of a sealed sample tube (6). The stirring drive device (7) includes a stirring motor (72), a connecting seat (73) set on the output end of the stirring motor (72), and magnets (74) set on both sides of the upper end of the connecting seat (73). The magnets (74) are set close to the bottom of the water tank (5), and the stirring motor (72) drives the two magnets (74) to rotate, thereby driving the stir bar (75) in the sealed sample tube to rotate.

8. The microsphere release testing system as described in claim 1, characterized in that, The bottom of the sealing cap (61) is provided with a sealing part (62) for embedding into the upper opening of the sealing sample tube (6). A sealing ring (63) is sleeved on the outside of the sealing part (62), so that the sealing part (62) can be sealed by the sealing ring (63) pressing against the inner wall of the sealing sample tube (6).

9. The microsphere release testing system as described in claim 1, characterized in that, The injection sampling pump (2) integrates a control system, which includes a PLC controller and a touch screen (21). The PLC controller is electrically connected to the touch screen (21), the stirring drive device (7), the temperature control device (8), the water level control device (9), the injection sampling pump (2), and the temperature probe socket (68).

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