An in-vitro dynamic simulation device and an in-vitro dynamic simulation test method

Abstract

The present application relates to a kind of in-vitro dynamic simulation device and in-vitro dynamic simulation test method, in-vitro dynamic simulation device includes working liquid storage device, liquid delivery system, spraying device, silica gel pipe and stress device;Liquid delivery system is used to deliver working liquid in working liquid storage device to spraying device;Spraying device is located above silica gel pipe, for working liquid is sprayed into silica gel pipe;Silica gel pipe is used to simulate ureter, silica gel pipe is placed vertically;Stress device includes cylindrical shell, motor, elastic convex strip, control panel;In-vitro dynamic simulation test method is that the in-vitro dynamic simulation device described above is used to evaluate the anti-calcification performance of ureteral stent in-vitro dynamic simulation test method and the in-vitro dynamic simulation test method for evaluating the anti-bacterial adhesion performance of ureteral stent.The device of the present application is simple in structure, method is easy to operate, so that in-vitro simulation test result is closer to clinical result, and product development direction is optimized.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology and relates to an in vitro dynamic simulation device and an in vitro dynamic simulation testing method. Background Technology

[0002] A ureteral stent is a minimally invasive surgical device used to relieve obstruction, support the wall of a narrowed ureteral segment, and drain urine from the kidney to the bladder. It is commonly used after urological procedures and conditions such as ureteroscopy, extracorporeal shock wave lithotripsy, ureteronephroureteral junction obstruction, and malignant ureteral obstruction to maintain and promote urine flow from the kidney to the bladder, help heal ureterostomies, and eliminate hydronephrosis and urinary leakage.

[0003] Ureteral stents can be used clinically for short periods, such as a few days, or for months or even years, depending on the cause and treatment process. As the stent remains in the body for an extended period, calcification occurs on its surface, eventually leading to stone coverage, infection, and re-obstruction of the ureter. Consequently, it fails to achieve its intended drainage and support effects, requiring removal and replacement, which significantly increases the burden on patients.

[0004] Literature review has confirmed that calcification deposition is related to factors such as the local flow field within the stent. By modifying the ureteral material, structural design, and coating, the adverse effects of calcification can be mitigated to some extent, thus enabling the development of ideal anti-calcification stents. Validating the effectiveness of the stent's anti-calcification design requires in vitro drainage testing, calcification simulation testing, animal experiments, and clinical trials. Among these, in vitro drainage testing and calcification simulation testing provide timely feedback on the design's effectiveness and are crucial for determining subsequent research directions and costs.

[0005] When patients undergo interventional treatment in clinical practice, ureteral stents not only come into contact with and react to human tissues and fluids, but are also subjected to mechanical forces such as ureteral compression and peristalsis. However, in vitro calcification simulations in laboratory testing and enterprise R&D verification are mostly conducted in a constant temperature static environment, which cannot realistically simulate the in vivo usage environment in multiple dimensions. The test results also differ greatly from the actual clinical situation. Therefore, it is necessary to design a more realistic in vitro dynamic calcification simulation tester to advance the research and development of ureteral stents.

[0006] The paper "Ureteral double-stents performances towards corrosion after long-term dwelling in a dynamic invitro model" discloses an in vitro dynamic simulation test instrument for anti-calcification. It conducted a simulation experiment on ureteral stents of different material structures for up to 6 months to evaluate the anti-calcification performance of the stents. The instrument uses three silicone tubes to form three parallel sub-channels to simulate the ureter, but it can only test three stents at a time and is only suitable for laboratory testing.

[0007] Patent CN203929745U discloses a dynamic simulation degradation device for evaluating biodegradable ureteral stents, which is used to test the degradation performance of biodegradable ureteral stents. It can simultaneously test multiple samples and collect degradation products for subsequent analysis. However, the instrument lacks a flow rate adjustment and micro-flow monitoring system, making it difficult to control experimental variables.

[0008] The paper "A new hydrophilic biodegradable ureteral stent resistance encrustation both in vitro and in vivo" discloses an in vitro simulated anti-calcification testing device, consisting of a glass reservoir, a miniature peristaltic pump, and transparent silicone tubing for connecting the entire system. The artificial urine flow rate is maintained at 10 ml / min. However, this device lacks a flow rate regulation system, making it difficult to control experimental variables.

[0009] Patent CN114452033A discloses a method for testing the performance of ureteral stents by simulating human body conditions. However, this instrument changes the flow rate by driving the clamp to change the cross-sectional area of ​​the silicone tube, making it difficult to intuitively quantify the flow rate adjustment.

[0010] Patent CN203929745U discloses a dynamic simulation degradation device for evaluating biodegradable ureteral stents. Although it takes into account the design of a tube peristalsis device to simulate the peristalsis of the ureter in the body and to effectively squeeze the ureteral stent to simulate the normal urination process of the human body, it does not consider the problem of silicone tube displacement caused by friction when designing the size parameters of the squeezing device and the silicone tube stent. This will cause other mechanical effects on the tested stent in addition to the squeezing force, which greatly weakens the simulation and thus affects the simulation results. Summary of the Invention

[0011] To address the problems existing in the prior art, this invention provides an in vitro dynamic simulation device and an in vitro dynamic simulation testing method. Specifically, it provides two in vitro dynamic simulation devices (device A and device B): device A is used for evaluating the anti-calcification performance of ureteral stents, device A is used for evaluating the antibacterial adhesion performance of ureteral stents, and device B is used for evaluating the drainage effect of ureteral stents. The in vitro dynamic simulation device provided by this invention can realistically simulate the in vivo environment, making the evaluation results accurate and reliable, and closer to the clinical application effect; the in vitro dynamic simulation testing method provided by this invention provides a more accurate and timely verification platform for stent improvement development, thereby shortening the development cycle and saving costs.

[0012] To achieve the above objectives, the present invention adopts the following solution:

[0013] An in vitro dynamic simulation device (i.e., device A) includes a working fluid storage device, a fluid delivery system, a spray device, a silicone tube, and a stress device;

[0014] The working fluid storage device is used to simulate the renal pelvis;

[0015] The liquid delivery system is used to deliver the working liquid from the working liquid storage device to the spraying device;

[0016] The spray device is located above the silicone tube and is used to spray the working liquid evenly into the silicone tube so that the working liquid flow rate and flow rate are the same for the test sample at any position.

[0017] Silicone tubing is used to simulate the ureter. The silicone tubing is placed vertically and is fixed by a groove, making it easy to replace. The silicone tubing is made of modified silicone with good hydrophilicity to ensure that its anti-calcification performance can support calcification simulation experiments for more than 12 months.

[0018] The stress device is used to simulate the unique cyclical contraction and relaxation of the ureter during human urination. Its overall outer diameter D1 is 15-25cm. It includes a cylindrical shell, a motor, elastic ribs, and a control panel. The cylindrical shell is placed vertically. The motor drives the cylindrical shell to rotate counterclockwise or clockwise around its central axis. There is one elastic rib, which is spirally wound around the central axis of the cylindrical shell and fixed to it. The control panel controls the speed and direction of the cylindrical shell's rotation via the motor.

[0019] The silicone tube is fixed to the outside of the cylindrical shell and is squeezed by elastic protrusions. The radial compression length D2 of the silicone tube is 0.12-0.3cm, and the distance H2 between adjacent compression points on each silicone tube is 2-5cm. Driven by the motor, the silicone tube is squeezed by the elastic protrusions to form rhythmic peristalsis. The peristalsis is transmitted from the renal pelvis to the bladder along the muscle wall at intervals of 10-60 seconds. The speed of peristalsis is determined by physiological mechanisms and is usually 20-30mm / s. The stress device parameters are set in accordance with the above physiological performance, thereby effectively simulating the normal urination process of the human body.

[0020] One of the technical problems this invention aims to solve is that existing technologies, when designing the dimensions of the extrusion device and the silicone tube support, fail to consider the displacement of the silicone tube caused by friction. This results in mechanical forces on the tested support other than the extrusion force, significantly weakening the simulation and affecting the simulation results. The stress device of this invention uses a control panel to change the operating frequency and direction of the motor, causing the elastic protrusion attached to the outside of the cylindrical motor to rotate. The elastic protrusion directly presses against the silicone tube. When set to forward operation, the elastic protrusion rhythmically presses down on the silicone tube and also generates friction with it. As the friction increases, when it reaches a certain value, the silicone tube may shift with the device's operating direction, thus displacing. When set to reverse operation, the elastic protrusion presses upward on the silicone tube, applying a force within a suitable range to the displaced tube, causing it to shift in the opposite direction and return to its original position, thereby solving the problem of silicone tube displacement caused by friction. Furthermore, this invention only uses reverse operation to adjust the position of the silicone tube when it slightly deviates from the track.

[0021] As a preferred technical solution:

[0022] As described above, the in vitro dynamic simulation device has a working fluid storage device with a capacity of 500mL-3L. It is tightly fitted to the external pipeline to reduce the possibility of contact with the external environment and avoid the introduction of external bacteria. The working fluid storage device has a built-in stirrer and a water bath system. The stirrer can prevent the working fluid from prematurely calcifying and precipitating in the storage device, which would affect the results of the in vitro simulation experiment. The water bath system has a heating function for the working fluid, which can not only achieve a constant temperature of 37°C, keeping the working fluid, including urine from healthy adult volunteers, ordinary artificial urine, calcified urine, bacterial urine, and PBS buffer, at the normal human body temperature, but also can conduct accelerated experiments in the temperature range of 37-65°C.

[0023] As described above, the in vitro dynamic simulation device has a stepless adjustable liquid delivery system. The liquid delivery system uses a micro peristaltic pump to adjust the working liquid flow rate (specifically, the working liquid flow rate is adjusted by changing the frequency of the micro flow pump). At the same time, a micro flow monitoring system (the functional component is a gear flow transmitter) monitors the flow rate in real time to facilitate the control of experimental variables and improve the repeatability of experimental results. The total flow rate adjustment range of the liquid delivery system is 0-240 ml / min.

[0024] The second technical problem that this invention aims to solve is that existing devices lack a flow rate regulation system, making it difficult to intuitively quantify flow rate regulation, and they also lack a flow rate regulation and micro-flow monitoring system, making it difficult to control experimental variables. This invention solves this problem by setting up a micro-peristaltic pump and a micro-flow monitoring system.

[0025] As described above, the in vitro dynamic simulation device has 12-24 spray holes in the spray device; the number of silicone tubes corresponds one-to-one with the number of spray holes in the spray device, and all silicone tubes are distributed around the central axis of the cylindrical shell; during use, the ureteral stent is placed in the silicone tube, which can simultaneously test up to 12-24 ureteral stents of different specifications, reducing the uncertainty caused by multiple tests and making the test results more accurate; the flow rate in a single silicone tube can be adjusted from 0-20 ml / min, thus simulating the average urine flow rate before and after urination of the entire unilateral kidney and during the urination process.

[0026] The third technical problem that this invention aims to solve is that existing technologies can only test three supports at a time, which is only suitable for laboratory testing; this invention solves this problem by adding a silicone tube.

[0027] As described above, in an in vitro dynamic simulation device, a detachable fork device is provided between the spray nozzles of the spray device and the silicone tubes. The fork device is used to adjust the number of open silicone tube channels during the experiment. The fork device is a circular plate or ring-shaped structure, with its central axis coinciding with the central axis of the cylindrical shell. It has 6-12 through holes distributed around the central axis. The fork device controls whether the through holes connect or disconnect the spray nozzles of the spray device and the silicone tubes by adjusting its own rotation angle around the central axis. Since the fork device is detachable, it can be removed when there are many test samples to ensure all channels are unobstructed. The fork device can be made of high-density stainless steel. This invention, by setting the fork device, can meet the needs of testing 6, 12, or 24 support samples in the same batch. When the number of samples is small or drainage tests are performed, the test error can be reduced.

[0028] As described above, in an in vitro dynamic simulation device, the inner diameter of the silicone tube is 3.5-6.5 mm, and the length H1 is 16-25 cm. The inner diameter of the silicone tube is the same at all positions, or the inner diameter of the lower end of the silicone tube is smaller than the inner diameter of other positions. The ureteral stents being tested are of different models and have different diameters. If the diameter is much smaller than the inner diameter of the silicone tube, it will leave the predetermined position and slip into the recovery chamber. Setting the inner diameter of the lower end of the silicone tube to be smaller than the inner diameter of other positions can avoid this situation.

[0029] In the aforementioned in vitro dynamic simulation device, the lower end of the silicone tube is connected to a working fluid storage device.

[0030] The in vitro dynamic simulation device described above also includes a visualization platform for observing the calcification process and the flow of the working fluid; the silicone tube and the stress device are located inside the visualization platform; the visualization platform is made of translucent resin by 3D printing.

[0031] This invention also provides an in vitro dynamic simulation test method for evaluating the anti-calcification performance of ureteral stents. The method uses the in vitro dynamic simulation device (i.e., device A) as described above. The specific process is as follows: After the ureteral stent is placed in the silicone tube, artificial urine at a temperature of 37°C is continuously passed through the silicone tube at a flow rate of 4-10 ml / min by a working fluid storage device, a fluid delivery system, and a spray device. At the same time, the silicone tube is continuously squeezed at a speed of 20-30 mm / s by a stress device to simulate the effect of ureteral peristalsis. After a set time is reached, the ureteral stent is removed, and its surface morphology, calcification thickness, and calcification composition are analyzed and characterized.

[0032] Meanwhile, this invention also provides an in vitro dynamic simulation test method for evaluating the antibacterial adhesion performance of ureteral stents. The method uses the in vitro dynamic simulation device (i.e., device A) described above. The specific process is as follows: After the ureteral stent is placed inside a silicone tube, artificial urine containing bacteria at a temperature of 37°C is continuously passed through the silicone tube at a flow rate of 4-10 ml / min, controlled by a working fluid storage device, a fluid delivery system, and a spray device. Simultaneously, a stress device continuously compresses the silicone tube at a speed of 20-30 mm / s to simulate ureteral peristalsis. After a set time, the ureteral stent is removed, and the amount of bacteria adhering to its surface is measured. To ensure the accuracy of the experimental results, the entire device must be sterilized before testing, and the instrument must be placed in a sterile environment.

[0033] In addition, the present invention also provides another in vitro dynamic simulation device (i.e., device B), including a medical injector, a silicone tube, a stress device, a micro-flow rate monitoring system and a working fluid collection device (such as a measuring cylinder, etc.);

[0034] The medical syringe is located above the silicone tubing and is used to inject the working fluid into the silicone tubing.

[0035] The silicone tubing is used to simulate the ureter and is placed vertically.

[0036] The stress device includes a cylindrical shell, a motor, elastic ribs, and a control panel; the cylindrical shell is placed vertically; the motor drives the cylindrical shell to rotate counterclockwise or clockwise around its own central axis; there is one elastic rib, which is spirally wound around the central axis of the cylindrical shell and fixed to it; the control panel is used to control the speed and direction of the rotation of the cylindrical shell through the motor;

[0037] The silicone tube is fixed to the outside of the cylindrical shell and is squeezed by elastic protrusions. The radial compression length D2 of the silicone tube is 0.12-0.3cm, and the distance H2 between adjacent compression points on each silicone tube is 2-5cm.

[0038] The lower end of the silicone tube is connected to a micro-flow rate monitoring system;

[0039] The micro-flow rate monitoring system is connected to the working fluid collection device (such as a measuring cylinder).

[0040] In addition, the present invention also provides an in vitro dynamic simulation test method for evaluating the drainage effect of ureteral stents, using the in vitro dynamic simulation device (i.e., device B) as described above. The specific process is as follows: First, the working fluid is controlled to pass through the silicone tube by a medical injector, and at the same time, the silicone tube is continuously squeezed at a speed of 20-30 mm / s by a stress device to achieve the effect of ureteral peristalsis. The flow rate and velocity of the working fluid are monitored by a micro-flow rate monitor. Then, after the ureteral stent is placed in the silicone tube, the above operation is repeated. The flow rate difference and velocity difference of the working fluid before and after the ureteral stent is placed are calculated.

[0041] Beneficial effects

[0042] (1) An in vitro dynamic simulation device of the present invention can simulate and quantify the drainage effect of a stent under rhythmic compression of the ureter by disassembling part of the system.

[0043] (2) The in vitro dynamic simulation test method of the present invention can be used to test the anti-calcification performance of various materials and structural parameters of ureteral stents, such as polymers, metals, biodegradable materials, and drug-loaded materials.

[0044] (3) An in vitro dynamic simulation device of the present invention can simultaneously test 1-24 ureteral stents, and the urine is changed every 10 hours during the test, which realizes the effective simulation of real metabolic conditions and ensures the accuracy of test results.

[0045] (4) An in vitro dynamic simulation device of the present invention, by designing a stepless adjustable liquid delivery system and a micro flow monitoring system, can effectively control experimental variables, make flow rate adjustment intuitive and quantifiable, thereby improving the repeatability of experimental results;

[0046] (5) An in vitro dynamic simulation device of the present invention can effectively control the experimental cycle by setting a water bath system with heating function, thereby shortening the research and development cycle and saving costs.

[0047] (6) An in vitro dynamic simulation device of the present invention effectively prevents the blockage of degradation products by using modified silicone tubes with good hydrophilicity.

[0048] (7) The in vitro dynamic simulation test method of the present invention simulates the process of urine flowing from the kidney to the ureter and then to the bladder, especially the stress change after the implantation of the ureteral stent. At the same time, the temperature control, compression rhythm and urine flow rate of the instrument are closer to the real environment of the human body, making the in vitro simulation test results closer to the clinical results and optimizing the product development direction. Attached Figure Description

[0049] Figure 1 This is a three-dimensional structural diagram of an in vitro dynamic simulation device according to the present invention;

[0050] Figure 2 This is a schematic diagram of the stress device structure in this invention;

[0051] Figure 3 This is a schematic diagram of the axial cross-sectional structure of the stress device in this invention;

[0052] Figure 4 This is a schematic diagram of the variable diameter silicone tube in the embodiment;

[0053] Among them, 1-working liquid storage device, 2-water bath system, 3-liquid delivery system, 4-micro flow monitoring system, 51-silicone tube, 53-shift fork device, 6-stress device, 61-control panel, 62-motor, 63-elastic convex strip, 64-cylindrical shell, 7-visual platform, 8-spraying device. Detailed Implementation

[0054] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0055] Example 1

[0056] An in vitro dynamic simulation device, such as Figures 1-3 As shown, it includes a working fluid storage device 1, a fluid delivery system 3, a spray device 8, a silicone tube 51, a stress device 6, a visualization platform 7, and a shift fork device 53;

[0057] The working fluid storage device 1 has a built-in agitator and water bath system 2;

[0058] The liquid delivery system 3 uses a miniature peristaltic pump (Nanjing Nengbiao Electromechanical Equipment Co., Ltd., 102R / D) to regulate the flow rate of the working liquid, and a micro flow monitoring system 4 (Hefei Kangyi Measurement and Control Technology Co., Ltd., KYLC-A50) to monitor the flow rate in real time; the liquid delivery system 3 is used to deliver the working liquid in the working liquid storage device 1 to the spraying device 8.

[0059] The spray device 8 is located above the silicone tube 51, and has 12-24 spray holes; the spray device 8 is used to spray the working liquid into the silicone tube 51.

[0060] like Figure 2 and Figure 3As shown, the stress device 6 includes a cylindrical housing 64, a motor 62, elastic protrusions 63, and a control panel 61; the cylindrical housing 64 is placed vertically; the motor 62 is used to drive the cylindrical housing 64 to rotate counterclockwise or clockwise around its own central axis; the elastic protrusions 63 are one in number and are spirally wound around the central axis of the cylindrical housing 64 and fixed to the cylindrical housing 64; the control panel 61 is used to control the speed and direction of rotation of the cylindrical housing 64 through the motor 62.

[0061] like Figure 2 As shown, the silicone tubes 51 are vertically fixed to the outside of the cylindrical shell 64 and distributed around the central axis of the cylindrical shell 64; the number of silicone tubes 51 corresponds one-to-one with the number of spray holes in the spray device 8; the inner diameter of the silicone tubes 51 is 3.5-6.5mm, and the length H1 is 16-25cm. The inner diameter of the silicone tubes 51 is the same at all positions, or the inner diameter at the lower end of the silicone tubes 51 is smaller than the inner diameter at other positions (e.g., ...). Figure 4 (as shown);

[0062] like Figure 3 As shown, the silicone tube is squeezed by the elastic protrusion 63, the radial compression length D2 is 0.12-0.3cm, and the distance H2 between adjacent compression points on each silicone tube is 2-5cm; the silicone tube 51 is used to simulate the ureter; the lower end of the silicone tube 51 is connected to the working fluid storage device 1.

[0063] Both the silicone tube 51 and the stress device 6 are located inside the visualization platform 7;

[0064] The shift fork device 53 is a detachable circular plate or ring structure set between the spray hole of the spray device 8 and the silicone tube 51, with its central axis coinciding with the central axis of the cylindrical housing 64. The shift fork device 53 is provided with 6-12 through holes distributed around the central axis. The shift fork device 53 controls whether the through holes are connected to or not connected to the spray hole of the spray device 8 and the silicone tube 51 by adjusting the angle of its own rotation around the central axis.

[0065] Example 2

[0066] An in vitro dynamic simulation device includes a medical syringe, a silicone tube, a stress device, a micro-flow rate monitoring system (Hefei Kangyi Measurement and Control Technology Co., Ltd., KYLC-A50), and a working fluid collection device.

[0067] The medical syringe is located above the silicone tubing and is used to inject the working fluid into the silicone tubing.

[0068] The stress device includes a cylindrical shell, a motor, elastic ribs, and a control panel; the cylindrical shell is placed vertically; the motor drives the cylindrical shell to rotate counterclockwise or clockwise around its own central axis; there is one elastic rib, which is spirally wound around the central axis of the cylindrical shell and fixed to it; the control panel is used to control the speed and direction of the rotation of the cylindrical shell through the motor;

[0069] The silicone tube is vertically fixed to the outside of the cylindrical shell and is compressed by elastic protrusions. The radial compression length D2 of the silicone tube is 0.12-0.3cm, and the distance H2 between adjacent compression points on each silicone tube is 2-5cm. The silicone tube is used to simulate the ureter.

[0070] The lower end of the silicone tube is connected to a micro-flow rate monitoring system;

[0071] The micro-flow rate monitoring system is connected to the working fluid collection device (such as a measuring cylinder).

[0072] Example 3

[0073] An in vitro dynamic simulation test method for evaluating the anti-calcification performance of ureteral stents, using the in vitro dynamic simulation device of Example 1, the specific process is as follows:

[0074] (1) Prepare 8 ureteral stents with anti-calcification surface treatment, 8 ureteral stents without anti-calcification surface treatment, and 8 commercial ureteral stents, each with a tube length of 18cm; take 1 stent of each of the 3 different types and place them into the same silicone tube.

[0075] (2) Place the entire device in a sterile, closed space with controllable CO2 concentration; after ensuring that the liquid circuit system of the entire device is interconnected, inject 600ml of artificial urine into the working liquid storage device, set the temperature of the water bath system to 37℃, and turn on the stirrer; control the artificial urine to flow continuously through the silicone tube at a flow rate of 10ml / min through the liquid delivery system, and control the silicone tube to continuously peristalse at a speed of 20mm / s through the stress device;

[0076] (3) Start the in vitro dynamic calcification simulation, record the start time, urine flow rate, urine pH in the first 10 hours (once per hour in the first 10 hours) and the 24th hour (starting from the first time of changing artificial urine each week as hour 0); replace 200ml of fresh artificial urine every 10 hours; take weeks as time nodes, and place a set of ureteral stent samples into the silicone tube one week, two weeks, three weeks, four weeks, five weeks, six weeks and seven weeks after the start of the experiment. Each set of ureteral stents placed consists of one ureteral stent with anti-calcification surface treatment, one ureteral stent without anti-calcification surface treatment and one commercial ureteral stent;

[0077] (4) After the eighth week of the experiment, the experiment was stopped, all ureteral stents were removed from the in vitro dynamic simulation device and dried in a vacuum oven at 37°C for 48 hours; the morphology, calcification thickness and calcification composition of the sample surface were analyzed and characterized.

[0078] Example 4

[0079] An in vitro dynamic simulation test method for evaluating the antibacterial adhesion performance of ureteral stents, using the in vitro dynamic simulation device of Example 1, the specific process is as follows:

[0080] (1) Prepare four ureteral stents each with an anti-calcification surface treatment, a non-anti-calcification surface treatment, and a commercially available ureteral stent, all with a tube length of 18cm; take one stent of each of the three different types and place them into the same silicone tube; prepare a solution with an approximate concentration of 1×10⁻⁶. 9 A 10 mL solution of Proteus mirabilis (ATCC29906) at cfu / mL was inoculated into artificial urine to obtain a total volume of 400 mL of artificial urine containing bacteria. The artificial urine containing bacteria was then incubated in a 37°C electric thermostatic shaker incubator for 16 h.

[0081] (2) Place the entire device in a sterile, closed space with controllable CO2 concentration; after ensuring that the liquid circuit system of the entire device is interconnected, inject all the sterile artificial urine into the working liquid storage device, set the temperature of the water bath system to 37°C, and turn on the stirrer; control the sterile artificial urine to flow continuously through the silicone tube at a flow rate of 6 ml / min through the liquid delivery system, and control the silicone tube to continuously peristalse at a speed of 20 mm / s through the stress device;

[0082] (3) Start the in vitro dynamic simulation of the antibacterial adhesion performance of ureteral stents and record the start time (antibacterial adhesion mainly focuses on the amount of bacterial adhesion after the ureteral stent simulation experiment). With 4h as the time node, a set of ureteral stent samples were placed into the silicone tube again 4h and 8h after the start of the experiment. Each set of ureteral stents included one ureteral stent with anti-calcification surface treatment, one ureteral stent without anti-calcification surface treatment, and one commercial ureteral stent.

[0083] (4) After the experiment was completed in 12 hours, the experiment was stopped, all ureteral stents were removed from the in vitro dynamic simulation device, and the amount of bacteria adhering to the stent surface was determined by the inverted plate coating method.

[0084] Example 5

[0085] An in vitro dynamic simulation test method for evaluating the drainage effect of a ureteral stent, using the in vitro dynamic simulation device of Example 2, the specific process is as follows:

[0086] (1) Fix the medical syringe to the upper end of the silicone tube and connect it to the silicone tube. Disconnect the two-way tube between the lower end of the silicone tube and the working liquid storage device 1. Connect a micro flow rate monitor and a separately placed 250ml graduated cylinder. Place the entire device in a sterile, closed space with controllable CO2 concentration.

[0087] (2) Control the silicone tube to continuously peristalse at a speed of 20 mm / s through the stress device; set the injection rate and liquid volume of the medical injector; after the instrument is running stably, start recording the injection time and the flow rate and flow rate displayed by the micro-flow rate monitor.

[0088] (3) Place a ureteral stent with a tube length of 18cm and an outer diameter of 1.6mm into the silicone tube of the extracorporeal dynamic simulation device; repeat step (2);

[0089] (4) Statistical analysis of the flow velocity and flow rate difference before and after the ureteral stent is inserted into the silicone tube; by using different ureteral stents, the drainage effect of ureteral stents with different parameters is compared.

Claims

1. An in-vitro dynamic simulation device, characterized in that, The device comprises a working liquid storage device (1), a liquid delivery system (3), a spraying device (8), a silica gel tube (51) and a stress device (6); The liquid delivery system (3) is used for delivering the working liquid in the working liquid storage device (1) to the spraying device (8); The liquid delivery system (3) is adjusted by a micro peristaltic pump to regulate the flow rate of the working liquid, and the flow rate is monitored in real time by a micro flow monitoring system (4); The spraying device (8) is located above the silica gel tube (51) and is used for spraying the working liquid into the silica gel tube (51); The silica gel tube (51) is used for simulating a ureter, and the silica gel tube (51) is vertically placed; The stress device (6) comprises a cylindrical shell (64), a motor (62), an elastic protrusion (63) and a control panel (61); the cylindrical shell (64) is vertically placed; the motor (62) is used for driving the cylindrical shell (64) to rotate counterclockwise or clockwise around the central axis thereof; the number of the elastic protrusions (63) is one, and each elastic protrusion (63) is spirally wound around the central axis of the cylindrical shell (64) and fixed on the cylindrical shell (64); the control panel (61) is used for controlling the speed and direction of the rotation of the cylindrical shell (64) by the motor (62); when the motor (62) operates in the forward direction, the elastic protrusion (63) rubs against the silica gel tube (51), and as the friction force increases, when the friction force reaches a certain value, the silica gel tube (51) deviates from the operating direction of the stress device (6) and is displaced; when the motor (62) operates in the reverse direction, the elastic protrusion (63) presses the silica gel tube (51) upward, and an opposite and appropriate force is applied to the displaced silica gel tube (51) to make the silica gel tube (51) deviate in the reverse direction and return to the original position, thereby solving the displacement problem of the silica gel tube (51) caused by friction; The silica gel tube (51) is fixed outside the cylindrical shell (64) and is pressed by the elastic protrusion (63), and the radial pressing length D2 of the silica gel tube is 0.12-0.3 cm, and the distance H2 between adjacent pressing points on each silica gel tube is 2-5 cm.

2. An in-vitro dynamic simulation apparatus according to claim 1, wherein, The number of the spraying holes of the spraying device (8) is 12-24; the number of the silica gel tubes (51) is the same as that of the spraying holes of the spraying device (8), and the silica gel tubes (51) and the spraying holes of the spraying device (8) are one-to-one corresponding, and all the silica gel tubes (51) are distributed around the central axis of the cylindrical shell (64).

3. An in-vitro dynamic simulation apparatus according to claim 2, wherein, A detachable yoke device is arranged between the spraying holes of the spraying device (8) and the silica gel tubes (51); the yoke device is in the form of a circular plate or a circular ring, the central axis thereof coincides with the central axis of the cylindrical shell (64), and 6-12 through holes are arranged around the central axis of the yoke device; the yoke device controls the communication or non-communication between the through holes and the spraying holes of the spraying device (8) and the silica gel tubes (51) by adjusting the rotation angle of the yoke device around the central axis.

4. An in-vitro dynamic simulation apparatus according to claim 1, wherein, The inner diameter of the silica gel tube (51) is 3.5-6.5 mm, and the length H1 is 16-25 cm; the inner diameters of the silica gel tube (51) at different positions are the same, or the inner diameter of the lower end of the silica gel tube (51) is smaller than that of other positions.

5. An in-vitro dynamic simulation apparatus according to claim 1, wherein, The in-vitro dynamic simulation device further comprises a visualization platform (7); the silica gel tube (51) and the stress device (6) are located inside the visualization platform (7).

6. An in vitro dynamic simulation test method for evaluating the anti- calcification performance of a ureteral stent, characterized in that, The specific process is that after the ureteral stent is placed in the silica gel pipe (51), the artificial urine with a temperature of 37 DEG C is continuously passed through the silica gel pipe (51) at a flow rate of 4-10 ml / min by the working liquid storage device (1), the liquid delivery system (3) and the spraying device (8), and the silica gel pipe (51) is continuously extruded at a speed of 20-30 mm / s by the stress device (6) to simulate ureter peristalsis, and after a set time, the ureteral stent is taken out, and the morphology, calcification thickness and calcification composition of the surface of the ureteral stent are analyzed and characterized.

7. An in vitro dynamic simulation test method for evaluating the antibacterial adhesion property of a ureteral stent, characterized by, The specific process is that after the ureteral stent is placed in the silica gel pipe (51), the artificial urine with a temperature of 37 DEG C is continuously passed through the silica gel pipe (51) at a flow rate of 4-10 ml / min by the working liquid storage device (1), the liquid delivery system (3) and the spraying device (8), and the silica gel pipe (51) is continuously extruded at a speed of 20-30 mm / s by the stress device (6) to simulate ureter peristalsis, and after a set time, the ureteral stent is taken out, and the morphology, calcification thickness and calcification composition of the surface of the ureteral stent are analyzed and characterized.

8. An in-vitro dynamic simulation apparatus, characterized by, It comprises a medical injector, a silica gel pipe, a stress device, a micro-flow rate monitoring system and a working liquid collection device; The medical injector is located above the silica gel pipe and is used for injecting the working liquid into the silica gel pipe; The silica gel pipe is used for simulating the ureter, and the silica gel pipe is vertically placed; The stress device comprises a cylindrical shell, a motor, an elastic convex strip and a control panel; the cylindrical shell is vertically placed; the motor is used for driving the cylindrical shell to rotate counterclockwise or clockwise around the central axis thereof; the number of the elastic convex strip is one, and the elastic convex strip is spirally wound around the central axis of the cylindrical shell and fixed on the cylindrical shell; the control panel is used for controlling the speed and direction of the rotation of the cylindrical shell by the motor; when the motor operates in the forward direction, the elastic convex strip generates friction with the silica gel pipe, and as the friction force increases, when the friction force reaches a certain value, the silica gel pipe deviates from the operating direction of the stress device and is displaced; when the motor operates in the reverse direction, the elastic convex strip extrudes the silica gel pipe upwards, and gives the displaced silica gel pipe an opposite and appropriate force, so that the silica gel pipe deviates in the reverse direction and returns to the original position, thereby solving the problem of displacement of the silica gel pipe caused by friction; The silica gel pipe is fixed outside the cylindrical shell and is extruded by the elastic convex strip, the extruded length D2 of the silica gel pipe in the radial direction is 0.12-0.3 cm, and the spacing H2 between adjacent extruded points on each silica gel pipe is 2-5 cm; The lower end of the silica gel pipe is connected with the micro-flow rate monitoring system; The micro-flow rate monitoring system is connected with the working liquid collection device.

9. An in-vitro dynamic simulation test method for evaluating the drainage effect of a ureteral stent, characterized in that, The specific process is as follows: firstly, the working liquid is controlled to pass through the silicone tube by a medical injection device, and the silicone tube is continuously extruded at a speed of 20-30 mm / s by a stress device to simulate ureter peristalsis, and the flow and flow rate of the working liquid are monitored by a micro-flow rate monitor; secondly, after the ureter stent is placed in the silicone tube, the above operation is repeated; and finally, the flow and flow rate differences of the working liquid before and after the ureter stent is placed are calculated.

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