A flow cell method drug dissolution closed-loop sampling system and its usage method

Abstract

A closed-loop sampling system for drug dissolution by flow-through cell method and its use method, comprising a constant-temperature water bath system, a flow-through cell system, a lifting mechanism, a circulating heating system, a solvent monitoring system, a solvent circulation system and a sampling system; the constant-temperature water bath system includes a constant-temperature water bath frame, a constant-temperature water bath, a solvent cup holder, a solvent cup and a solvent cup cover; the flow-through cell system is arranged at the top of the constant-temperature water bath system; the lifting mechanism is arranged on one side of the constant-temperature water bath frame; the circulating heating system includes a heating device and a water circulation pump; the circulating inlet end of the solvent monitoring system is communicated with the heating device, and the circulating outlet end of the solvent monitoring system is respectively communicated with the solvent cup and the flow-through cell; the solvent circulation system includes a solvent circulation pump and a pulse valve; the sampling system includes a sampling mechanism, a sampling pipeline, a sampling valve and a sampling pump. The device of the present invention has a compact structure, high heating efficiency of the heating device, uniform water temperature distribution in the water bath, accurate water temperature control, and temperature and pressure monitoring of the solvent.

Description

Technical Field

[0001] The present invention relates to the technical field of medical experimental equipment applications, and particularly to a closed-loop sampling system for drug dissolution by the flow-through cell method and a usage method thereof. Background Art

[0002] With the rapid development of pharmaceutical technology, along with the birth of a large number of new pharmaceutical preparations and the current requirements for in vitro-in vivo correlation (IVIVC) of dissolution determination methods, traditional dissolution determination methods (such as paddle method, basket method, etc.) encounter many new problems when evaluating the quality of preparations, such as the determination of micro-dose pharmaceutical preparations, the formulation of new pharmaceutical preparations such as patches and microspheres, and how to solve the in vitro-in vivo correlation of immediate-release preparations. As a new method for checking dissolution concentration, the flow-through cell method mainly relies on a flowing solvent to continuously wash the preparation, which can well simulate the in vivo circulation of drugs in the human body. By selecting appropriate cell accessories, it is applicable to tablets, capsules, patches, microspheres, suppositories, suspensions, stents, implants, liposomes, etc.

[0003] For drug dissolution tests with relatively low drug dissolution concentration and slow dissolution rate, the drug dissolution amount accumulatively changes with time. It is necessary to use the flow-through cell method for closed-loop dissolution tests. In the existing closed-loop test process, after the drug is dissolved by the flushing of the solvent in the flow-through cell, the solvent circulates and enters the solvent cup. The solvent cup is heated separately in a water bath to keep the solvent at a temperature close to the actual human body temperature, and then the solvent in the solvent cup is sampled regularly, quantitatively, and in batches through a sampling system.

[0004] The existing flow-through cell method drug dissolution sampling system has the following defects:

[0005] 1. When controlling the temperature of the solvent in the solvent cup, a separate heating water tank is used to heat the solvent cup in a water bath. This water bath heating system and the dissolution system of the flow-through cell use two sets of devices. During the experiment, it is necessary to plug and fix the inlet and outlet pipes of the solvent cup to the inlet and outlet of the flow-through cell dissolution system, and at the same time, it is also necessary to plug and fix the inlet and outlet pipes of the heating system circulating water to the circulating water inlet and outlet of the flow-through cell dissolution system. The experimental operation process is very inconvenient; and the overall equipment of this structural form occupies a large area and the structural form is not compact enough.

[0006] 2. When heating the solvent cup in a water bath, a heating wire is directly placed in the heating water tank of the solvent cup to directly and locally heat the water in the tank. The temperature distribution in the tank is uneven, making it difficult to control the heat exchange temperature between the water and the solvent in the solvent cup; and during the circulation of the solvent, multi-point continuous temperature control of the solvent is not carried out to ensure that the solvent and the drug are at the best suitable temperature for the drug dissolution test. Summary of the Invention

[0007] To solve the above existing problems, the present invention discloses a closed-loop sampling system for drug dissolution by the flow-through cell method, and its specific technical solution is as follows: A closed-loop sampling system for drug dissolution by the flow-through cell method includes a constant-temperature water bath system, a flow-through cell system, a lifting mechanism, a circulating heating system, a solvent monitoring system, a solvent circulation system, and a sampling system;

[0008] The constant-temperature water bath system is used to keep the solvent in the solvent cup at a constant temperature; the constant-temperature water bath system includes a constant-temperature water tank frame, a constant-temperature water tank, a solvent cup holder, a solvent cup, and a solvent cup cover. The constant-temperature water tank is placed in the constant-temperature water tank frame; the solvent cup holder is arranged on the top surface of the constant-temperature water tank; the solvent cup is fitted into the solvent cup holder for limit fixation; the solvent cup cover is buckled on the top surface of each solvent cup;

[0009] The flow-through cell system is used for the process of flushing and dissolving the drug with the solvent; the flow-through cell system is arranged at the top of the constant-temperature water bath system. The flow-through cell system includes a flow-through cell frame, a flow-through cell, and a glass tube. The flow-through cell frame is arranged on one side of the top surface of the solvent cup holder. The flow-through cell is fixed on the flow-through cell frame and is arranged in a horizontal array; the glass tube is correspondingly sleeved on the outer wall of each flow-through cell; the solvent cup cover is hoisted with the flow-through cell frame through a clamping structure;

[0010] The lifting mechanism is used for the overall lifting and lowering of the flow-through cell system; the lifting mechanism is arranged on one side of the constant-temperature water tank frame. The bottom end of the lifting mechanism is fixed to the top surface of the constant-temperature water tank frame, and one side of the top end of the lifting mechanism is fixedly arranged with the side wall of the flow-through cell frame;

[0011] The circulating heating system is used for the water circulation heat exchange of the solvent in the solvent cup and the flow-through cell to achieve temperature control; the circulating heating system includes a heating device and a water circulation pump. The heating device is arranged on one side of the top surface of the solvent cup holder and on one side of the flow-through cell frame; the constant-temperature water tank circulates water between the flow-through cell system and the constant-temperature water tank through the water circulation pump via a pipeline;

[0012] The solvent monitoring system is used to monitor the temperature and pressure of the circulating solvent and to control the switching of the solvent circulation; the solvent monitoring system is arranged on the top of the heating device. The circulation inlet end of the solvent monitoring system is communicated with the heating device, and the circulation outlet end of the solvent monitoring system is respectively communicated with the solvent cup and the flow-through cell;

[0013] The solvent circulation system is used to circulate the solvent among the constant temperature water bath system, the flow cell system and the circulation heating system; the solvent circulation system includes a solvent circulation pump and a pulse valve, the output end of the solvent circulation pump is connected to the input end of the pulse valve through a pipeline, and after the output end of the pulse valve is connected to the circulation heating system, the flow cell system and the constant temperature water bath system in sequence through a pipeline, it is connected to the input end of the solvent circulation pump;

[0014] The sampling system is used to perform time-sharing quantitative sampling on the solvent in the solvent cup; the sampling system includes a sampling mechanism, a sampling pipeline, a sampling valve and a sampling pump, the sampling mechanism is connected to the inside of the solvent cup through the sampling pipeline, the sampling valve is arranged on the sampling pipeline, and the sampling pump is connected to the sampling pipeline.

[0015] Further, the constant temperature water tank frame includes a water tank bottom rod, a water tank bottom plate, water tank side plates, water tank frame bottom feet and a water tank back frame; the water tank bottom plate is arranged on the top surface of the water tank bottom rod, and is arranged on both sides, one side of the water tank bottom plate is turned up, and one side of the water tank bottom plate is turned down; the water tank side plates are arranged on both sides of the water tank bottom plate and are fixedly assembled with the water tank bottom plate through fasteners, and the tops of the two water tank side plates are fixedly assembled with the solvent cup holder through fasteners; the water tank frame bottom feet are arranged at the bottom end of the water tank bottom rod; the water tank back frame is arranged on one side of the water tank side plate.

[0016] Further, the constant temperature water tank is placed on the water tank bottom plate, the top side of the constant temperature water tank is assembled with the solvent cup holder through fasteners, and the side wall surface of the constant temperature water tank is limited by the water tank side plate.

[0017] Further, the flow cell frame includes side fixing blocks, a liquid collecting tank, a drain pipe, cushion blocks, a liquid tank top plate, a water area base, a water area upper cover, knobs, support rods, side fixing plates, mask connecting blocks, mask fixing rods, a flow cell mask, and a flow cell back plate; the side fixing blocks are arranged at both ends of the liquid collecting tank, and the side fixing blocks are assembled with the liquid collecting tank through fasteners; the cushion blocks are arranged at the bottom sides of both ends of the liquid collecting tank, and the cushion blocks are assembled with the side fixing blocks through fasteners; the side wall of the liquid collecting tank is provided with side holes of the liquid collecting tank, and the bottom end of the liquid collecting tank is provided with a bottom hole of the liquid collecting tank. One end of the drain pipe is assembled and communicated with the bottom hole of the liquid collecting tank, and the bottom end of the drain pipe penetrates through the solvent cup holder and extends into the constant temperature water tank; the liquid tank top plate is arranged on the top surface of the liquid collecting tank, and the liquid tank top plate is assembled with the liquid collecting tank through fasteners; the water area base is fixed on the top surface of the liquid tank top plate and is arranged in a horizontal array. A solvent inlet is provided at the center of the water area base, and one end of the solvent inlet is connected with a solvent inlet joint. A water area water inlet is provided on one side of the water area base, and the water area water inlet is connected with a water area water inlet joint; the water area upper cover is arranged on the top surface of the water area base. A fixing hole of the upper cover is provided at the center of the water area upper cover, and a water area water outlet is provided on one side of the water area upper cover. The water area water outlet is connected with a water area water outlet joint; knob fixing cylinders are provided on both sides of the top surface of the water area upper cover, and the knobs are inserted and connected with the knob fixing cylinders; the support rods are arranged on both outer sides of the water area base. The bottom end of the support rod is vertically fixed with the liquid tank top plate, and the top end of the support rod is vertically fixed with the bottom surface of the water area upper cover; the side fixing plates are arranged on both sides of the liquid tank top plate and are symmetrically arranged. The bottom end of each side fixing plate is fixed with the liquid tank top plate through fasteners; the mask connecting blocks are arranged on the top sides of each side fixing plate and are assembled with the side fixing plates through fasteners; both ends of the mask fixing rod are rotatably arranged with the mask connecting blocks on both sides through a rotating shaft; the flow cell mask is attached to the side wall of the mask connecting block, and the flow cell mask is assembled with the mask fixing rod through fasteners; the flow cell back plate is arranged on one side of the flow cell, and both sides of the flow cell back plate are assembled with the side fixing plates on both sides through fasteners.

[0018] Further, the length of the cushion block is longer than the width of the liquid collecting tank, and both ends of the cushion block extend out of both sides of the bottom surface of the liquid collecting tank; rubber feet are provided on the bottom surface of each side of the cushion block, and the rubber feet are fixed with both ends of the bottom surface of each cushion block through insertion; the cushion block is attached to the top surface of the solvent cup holder through the rubber feet.

[0019] Furthermore, the clamping structure includes a hoisting plate, a hoisting rod and a clamping ring. The hoisting plate is arranged on both sides of the liquid collecting tank. On each side, the hoisting plate is attached to the top surface of the cushion block and the side wall of the liquid collecting tank. The two ends of the hoisting plate are fixed to the cushion block through fasteners; the hoisting rod is arranged at the top end of the solvent cup rod, and the hoisting rod is vertically fixed to the solvent cup cover through threads. The top end of the hoisting rod is circumferentially grooved to form a hoisting rod top groove. The hoisting rod penetrates through the hoisting plate, and the clamping ring is embedded in the hoisting rod top groove to realize the hoisting setting of the solvent cup cover and the hoisting plate.

[0020] Furthermore, the number of liquid collecting tank bottom holes provided in the liquid collecting tank is two, and each drain pipe is arranged in alignment with each liquid collecting tank bottom hole; the end of the drain pipe is in a flange shape. One end of the drain pipe extends into the liquid collecting tank bottom hole, and the flange of the drain pipe is attached to the inner bottom surface of the liquid collecting tank. The drain pipe is vertically communicated with the liquid collecting tank through fasteners in cooperation with the liquid collecting tank.

[0021] Furthermore, the top surface of the water area base is in a stepped structure, forming a base step. A base sealing ring is circumferentially embedded on the side wall of the base step. The bottom end of the glass tube is sleeved on the outer wall of the base step to realize plug-in fixation. The glass tube and the water area base are sealed through the base sealing ring; the water area water inlet penetrates through the top surface of the base step.

[0022] Furthermore, the solvent inlet joint is arranged at the center of the top surface of the water area base, and the solvent inlet joint is vertically arranged with the water area base.

[0023] Furthermore, the water area upper cover is in a square structure; the center of the bottom surface of the water area upper cover is in a stepped structure, forming an upper cover step. An upper cover sealing ring is circumferentially embedded on the side wall of the upper cover step. The top end of the glass tube is sleeved on the outer wall of the upper cover step to realize plug-in fixation. The glass tube and the water area upper cover are sealed through the upper cover sealing ring; the water area water outlet penetrates through the bottom surface of the upper cover step.

[0024] Furthermore, the solvent inlet joint, the water area water inlet joint and the water area water outlet joint all adopt Luer connectors.

[0025] Furthermore, the bottom end of the knob extends into the corresponding knob fixing cylinder, and the knob is threadedly fixed to the knob fixing cylinder; a knob fixing piece is arranged on the side wall of each knob, and the knob fixing piece is vertically arranged with the knob.

[0026] Further, the circulating heating system further includes a water tank outlet pipe, a main water circulation pipe, a shunt tee, shunt pipes, return branch pipes, a make-up water tee, a make-up water pipe, a make-up water stop valve, a side branch tee, and a bypass pipe; one end of the water tank outlet pipe communicates with the bottom end of the constant temperature water tank, and one end of the water tank outlet pipe communicates with the suction end of the water circulation pump; one end of the main water circulation pipe communicates with the output end of the water circulation pump, and one end of the main water circulation pipe communicates with the shunt tee; one end of each shunt pipe communicates with one end of the shunt tee, and the shunt pipe is inserted into each water area inlet joint through a manifold; both ends of each return branch pipe are connected to a side hole of a liquid collecting tank and a water area outlet joint; the make-up water tee is arranged on the water tank outlet pipe, the make-up water pipe is connected to one end of the make-up water tee, and the make-up water stop valve is arranged on the make-up water pipe; the side branch tee is arranged on the main water circulation pipe, one end of the bypass pipe communicates with the side branch tee, and one end of the bypass pipe communicates with one side of the constant temperature water tank.

[0027] Further, the heating device includes a heating fixing plate, heating wires, connecting heads, straight connectors, connecting wires, a solvent inlet pipe, a solvent outlet pipe, and a heating shield; the heating fixing plate is embedded in the top surface of the solvent cup holder; the heating wires are arranged in the constant temperature water tank, and one end of each heating wire penetrates through the heating fixing plate and is fixedly inserted with the connecting head; the connecting wires are arranged on the top surface of the heating fixing plate, and both ends of the connecting wires are fixedly inserted with the connecting head; the plug connectors of the connecting wires and the plug connectors of the heating wires are respectively thread-fixed to both ends of the straight connector to connect the connecting wires and the heating wires; the solvent inlet pipe is arranged in the heating water tank, and one end of each solvent inlet pipe penetrates through the heating fixing plate and is fixedly inserted with the connecting head; the solvent outlet pipe is arranged in the heating water tank, and one end of each solvent outlet pipe penetrates through the heating fixing plate and is fixedly inserted with the connecting head, and the bottom end of the solvent inlet pipe is communicated with the bottom end of the solvent outlet pipe; the heating shield is buckled on the top surface of the heating fixing plate, and one end of the heating shield is rotatably connected to the constant temperature water tank frame through a movable hinge.

[0028] Further, the heating wires are arranged in two rows, each row of heating wires is arranged in two layers, and each layer of heating wires has a circular coiled pipe structure; the adjacent two heating wires connected by a single connecting wire are arranged obliquely in the upper and lower layers.

[0029] Further, the connecting wire has an inverted "U" shaped structure.

[0030] Further, the solvent inlet pipe is arranged at the center of the top surface of the heating fixing plate and between the heating wires; the solvent outlet pipe is arranged on one side of the top surface of the heating fixing plate.

[0031] Furthermore, the solvent monitoring system includes a detection frame, a three-way valve island, a pipe flushing valve island, a pressure valve, an optoelectronic switch, a diversion pipe, and a temperature sensor; the detection frame is arranged on the top surface of the heating mask, and the detection frame is fixedly arranged with the heating mask; the three-way valve island is arranged at one end inside the detection frame, and the three-way valve island is supported and fixed by a first bracket; the pipe flushing valve island is arranged at one end inside the detection frame, and the pipe flushing valve island is supported and fixed by a second bracket; the pressure valve is arranged in the middle inside the detection frame and on one side of the three-way valve island, a pressure valve fixing block is arranged outside the pressure valve, the pressure valve is embedded in the pressure valve fixing block, and the pressure valve fixing block is fixedly supported by a third bracket; the optoelectronic switch is arranged at one end inside the detection frame and on one side of the pressure valve, and the optoelectronic switch is fixed in the detection frame by a pipe clamp; the diversion pipe is arranged at the top end inside the detection frame and on one side of the pipe flushing valve island, and the diversion pipe is fixedly supported by a fourth bracket; the temperature sensor is vertically fixed at the bottom end of the diversion pipe, and the end of the temperature sensor extends into the inside of the diversion pipe; the solvent outlet pipe extends into the detection frame through a pipe and is communicated with the inlet end of the corresponding three-way valve island; the side-end outlet of the three-way valve island is communicated with one end of the corresponding pressure valve through a pipe; the other end of the pressure valve is communicated with a pipe, and the pipe is embedded in the pipe clamp; the top-end outlet of the three-way valve island is communicated with the bottom end of the corresponding pipe flushing valve island through a pipe; one end outlet of the pipe flushing valve island is communicated with the input port of the solvent cup cover through a pipe; one end outlet of the pipe flushing valve island is communicated with the corresponding diversion pipe through a pipe.

[0032] Furthermore, the detection frame includes a frame bottom plate, frame side plates, a frame back plate, a frame cover plate, and a frame handle; the frame side plates are symmetrically arranged on both sides, the top edge and the bottom edge of each frame side plate are bent, the bottom sides of the two frame side plates are fixed to the top surface of the heating mask, the frame bottom plate is arranged between the bottom sides of the two frame side plates and is fixed to the two frame side plates, and a frame bottom plate through hole is arranged on one side of the surface of the frame bottom plate; the cross section of the frame back plate is in a "C" shape structure, the frame back plate is arranged at one end of the two frame side plates, and the frame back plate is fixed to the two frame side plates; the frame cover plate is buckled on the top side of the frame side plates, and both sides of the frame cover plate are fixed to the top sides of the two frame side plates; the frame handle is arranged on one side of one frame side plate and is vertically fixed to the frame side plate.

[0033] Furthermore, the three-way valve island is arranged at the top end of the through hole of the rack bottom plate; the first bracket is arranged on one side of the three-way valve island, the cross-section of the first bracket is an "L"-shaped structure, the bottom surface of the first bracket is fixed to the rack bottom plate, and the top side surface of the second bracket is fixed to the side surface of the three-way valve island.

[0034] Furthermore, the lubricating valve island is arranged at the top of the three-way valve island; the second bracket is arranged at both ends of the lubricating valve island, the cross-section of the second bracket at each end is an "L"-shaped structure, the bottom surface of the second bracket at each end is fixed to the bottom plate of the rack, and the top side surface of the second bracket at each end is fixed to the end surface of the lubricating valve island, and the lubricating valve island and the three-way valve island are arranged in the same direction.

[0035] Furthermore, the pressure valves are arranged in a horizontal array, and each of the pressure valves is arranged in opposition to the outlet of the three-way valve island; the third bracket is arranged on the bottom side of the pressure valve, and the third bracket has a "Z"-shaped structure, the bottom surface of the third bracket is fixed to the bottom plate of the frame, and the top surface of the third bracket is fixed to the pressure valve fixing block.

[0036] Furthermore, the transverse array of the pipe clamps is arranged on the top surface of the frame bottom plate, the top surface of each pipe clamp is groove-shaped, forming a pipe clamp slot, and each pipe clamp slot is arranged in alignment with the pressure valve; the photoelectric switch is arranged on the top surface of the pipe clamp and spans the top surface of the pipe clamp slot.

[0037] Furthermore, the guide pipes are arranged in a horizontal array, the guide pipes and the lubrication valve island are arranged at the same height, and each of the guide pipes is arranged in alignment with the outlet of the lubrication valve island; the fourth bracket is arranged between the third bracket and the pipe clamp, the cross-section of the fourth bracket is a "匚"-shaped structure, the bottom surface of the fourth bracket is fixed to the frame bottom plate, and the guide pipe is arranged on the top surface of the fourth bracket.

[0038] Furthermore, the solvent circulation system also includes a first solvent tube, a second solvent tube, a third solvent tube, a fourth solvent tube and a fifth solvent tube; one end of the first solvent tube is connected to the top of the circulation pool, and one end of the first solvent tube is connected to the input port of the solvent cup cover; one end of the second solvent tube is connected to the output port of the solvent cup cover, and one end of the second solvent tube is connected to the suction end of the solvent circulation pump; one end of the third solvent tube is connected to the output end of the solvent circulation pump, and one end of the third solvent tube is connected to the input end of the pulse valve; one end of the fourth solvent tube is connected to the output end of the pulse valve, and one end of the fourth solvent tube is connected to the solvent inlet pipe; one end of the fifth solvent tube is connected to one end of the guide tube, and one end of the fifth solvent tube is connected to the solvent inlet of the circulation pool.

[0039] Further, the solvent circulation pump is a piston injection pump; the number of the solvent circulation pumps is two. One end of the second solvent pipe is respectively connected to the suction end of each solvent circulation pump through a manifold, and one end of the third solvent pipe is respectively connected to the output end of each solvent circulation pump through a manifold.

[0040] Further, the heating wire, the water circulation pump, the solvent circulation pump, the pulse valve, the sampling valve, the sampling pump, the three-way valve island, the pipe flushing valve island, the photoelectric switch, and the temperature sensor are electrically connected to an external controller through wires; the controller controls the set temperature value of the heating wire, and the controller controls the opening and closing of the water circulation pump, the solvent circulation pump, the pulse valve, the sampling valve, the sampling pump, the three-way valve island, and the pipe flushing valve island. The photoelectric switch uploads a signal to the controller, and the temperature sensor uploads temperature information to the controller.

[0041] A method for using a closed-loop sampling system for drug dissolution by the flow cell method is as follows:

[0042] 1. Support and fix the drug support structure in the flow cell, insert the flow cell into the fixing hole of the upper cover, plug and fix the bottom end of the flow cell to the solvent inlet joint, and then rotate the knob so that the knob fixing piece buckles on the end of the flow cell; connect one end of the flow cell to one end of the first solvent pipe to connect the flow cell to the solvent circulation system.

[0043] 2. Start the adjustment and lifting mechanism, lower the lifting mechanism to the lowest point, the lifting mechanism drives the flow cell system to the lowest position, and the solvent cup cover is pressed down to fit at the solvent cup hole.

[0044] 3. Start the heating operation of the heating wire, and the heating wire heats the water in the constant temperature water tank.

[0045] 4. Start the water circulation pump. The water in the constant temperature water tank is sucked into the suction end of the water circulation pump through the water tank outlet pipe. Through the pumping action of the water circulation pump, the water flows into the shunt pipe through the shunt three-way, and then through the manifold is respectively input into the glass tube through the water area inlet. After the glass tube is filled, it is injected into the liquid collection tank through the return branch pipe. The water in the liquid collection tank is re-injected into the constant temperature water tank through the drain pipe.

[0046] 5. Directly connect one outlet end of the pipe flushing valve island to the input port of the solvent cup cover through a conduit; start the solvent circulation pump. The solvent in the solvent cup is sucked into the suction end of the solvent circulation pump through the second solvent pipe. Through the pumping action of the solvent circulation pump, the solvent is sent to the pulse valve through the third solvent pipe. The pulse valve pulsates the solvent to simulate human blood circulation. The solvent enters the constant temperature water tank through the fourth solvent pipe for heat exchange. The solvent flows through the heating device and the solvent monitoring system and directly returns to the solvent cup; meanwhile, the solvent fills the diversion pipe to monitor the temperature of the solvent.

[0047] 6. When the temperature sensor monitors that the temperature of the solvent reaches 37°C, the output end of the diversion tube is communicated with the solvent inlet of the flow cell through the fifth solvent tube; the solvent flowing into the solvent monitoring system flows through the purge valve island and into the bottom end of the flow cell through the fifth solvent tube. After the solvent flushes with the drug, it is re-injected into the solvent cup through the first solvent tube.

[0048] 7. Start the sampling pump and open the sampling valve. The solvent in the solvent cup is sucked into the suction end of the sampling pump through the sampling pipeline and sent to the sampling mechanism through the pumping action of the sampling pump. The sampling mechanism performs time-sharing quantitative sampling.

[0049] The beneficial effects of the present invention are as follows:

[0050] 1. The present invention designs a closed-loop flow cell method drug dissolution sampling system for drug dissolution. The invention sets the flow cell system above the constant temperature water area system, and realizes the longitudinal lift between the flow cell system and the constant temperature water area system through the lifting mechanism. The two systems are integrally designed. One device can realize the drug dissolution of the flow cell and the function of circulating heat preservation of the water area. The system functions are integrally integrated. On the premise of ensuring the functionality of the device, the structure of the device is compact, the overall volume of the device is reduced, and it is convenient for the placement and transportation of the device.

[0051] 2. A circulating heating system is integrally arranged on one side of the constant temperature water tank system of the present device. In the circulating heating system, the water area of the constant temperature water tank is heated. The heating device fixes the heating wire in the form of a heating fixing plate. The heating wires are arranged in an array in the constant temperature water tank, and multiple groups of heating wires are inserted into the constant temperature water tank. The heating wires are well fixed. When the water circulates in the constant temperature water tank, there is no deviation of the heating wires, ensuring a good heating effect. At the same time, the present invention designs the heating wire as a coiled tube structure, which is arranged in a staggered manner up and down, greatly compressing the structural size of the heating wire and increasing the heat exchange area between the heating wire and the water area. By connecting the adjacent two heating wire structures with connecting wires, the heating wires are modularly arranged, further improving the heating effect of the heating wire. The heating wire cooperates with the water flow in the constant temperature water tank, and the temperature distribution in the water area is uniform, and the water area in the solvent cup can be accurately controlled at 37°C.

[0052] 3. The present invention is provided with a solvent monitoring system at the heating device, which controls the heating of the solvent and circulates the solvent between the heating device and the solvent cup for heating before the temperature reaches 37°C. When the solvent reaches 37°C, the solvent flows through the flow cell for drug dissolution circulation. By using the flow control valve island to switch the flow direction of the solvent, precise temperature control of the solvent can be achieved, and it is ensured that the solvent always operates at 37°C, realizing the temperature control of the solvent. The solvent monitoring system can also monitor the circulation pressure of the solvent. Through the function of the three-way valve island, it can detect that when the circulation pressure of the solvent is greater than 0.1 MPa, an audible and visual alarm can be given to warn the test personnel and ensure that the circulation pipeline of the solvent maintains a safe pressure circulation, and the safety performance of the device is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 It is a schematic diagram of the overall equipment structure of the present invention.

[0054] Figure 2 It is a schematic diagram of the structure of the constant temperature water bath system of the present invention.

[0055] Figure 3 It is a schematic diagram of the external structure of the flow cell system of the present invention.

[0056] Figure 4 It is a schematic diagram of the structure at the clamping connection of the flow cell system of the present invention.

[0057] Figure 5 It is a schematic diagram of the structure of the solvent cup cover of the present invention.

[0058] Figure 6 It is a schematic diagram of the internal structure of the flow cell system of the present invention.

[0059] Figure 7 It is a front view of the flow cell system of the present invention.

[0060] Figure 8 It is a front sectional view of the flow cell system of the present invention.

[0061] Figure 9 It is a sectional view schematic diagram of the flow cell of the present invention.

[0062] Figure 10 It is a front view of the heating device and the solvent monitoring system of the present invention.

[0063] Figure 11 It is a partial structure schematic diagram of the heating device and the detection rack of the present invention.

[0064] Figure 12 It is a schematic diagram of the structure of the heating device of the present invention.

[0065] Figure 13 It is a schematic diagram of the structure of the sampling system of the present invention.

[0066] Figure 14 It is a schematic flow diagram of the water circulation heating system of the present invention.

[0067] Figure 15 It is a schematic flow diagram of the solvent circulation system of the present invention.

[0068] Figure 16 It is a schematic flow diagram of the sampling system of the present invention.

[0069] List of reference numerals:

[0070] Constant temperature water area system 1;

[0071] Constant temperature water tank frame 1-1, water tank bottom rod 1-1-1, water tank bottom plate 1-1-2, water tank side plate 1-1-3, water tank frame foot 1-1-4, water tank back frame 1-1-5, constant temperature water tank 1-2, solvent cup holder 1-3, solvent cup 1-4, solvent cup cover 1-5;

[0072] Flow cell system 2;

[0073] Flow cell frame 2-1, side fixing block 2-1-1, liquid collecting tank 2-1-2, side hole of liquid collecting tank 2-1-2-1, bottom hole of liquid collecting tank 2-1-2-2, drain pipe 2-1-3, cushion block 2-1-4, rubber foot 2-1-4-1, liquid tank top plate 2-1-5, water area base 2-1-6, solvent inlet 2-1-6-1, solvent inlet joint 2-1-6-2, water area water inlet 2-1-6-3, water area water inlet joint 2-1-6-4, base layer platform 2-1-6-5, base sealing ring 2-1-6-6, water area upper cover 2-1-7, upper cover fixing hole 2-1-7-1, water area water outlet 2-1-7-2, water area water outlet joint 2-1-7-3, knob fixing cylinder 2-1-7-4, upper cover layer platform 2-1-7-5, upper cover sealing ring 2-1-7-6, knob 2-1-8, knob fixing piece 2-1-8-1, support rod 2-1-9, side fixing plate 2-1-10, mask connecting block 2-1-11, mask fixing rod 2-1-12, flow cell mask 2-1-13, flow cell back plate 2-1-14, flow cell 2-2, glass tube 2-3, clamping structure 2-4, lifting plate 2-4-1, lifting rod 2-4-2, top groove of lifting rod 2-4-2-1, snap ring 2-4-3;

[0074] Lifting mechanism 3;

[0075] Circulation heating system 4;

[0076] Heating device 4-1, heating fixed plate 4-1-1, heating wire 4-1-2, connector 4-1-3, straight connector 4-1-4, connecting wire 4-1-5, solvent inlet pipe 4-1-6, solvent outlet pipe 4-1-7, heating mask 4-1-8, water circulation pump 4-2, water tank outlet pipe 4-3, main water circulation pipe 4-4, shunt tee 4-5, shunt pipe 4-6, return branch pipe 4-7, make-up water tee 4-8, make-up water pipe 4-9, make-up water stop valve 4-10, bypass tee 4-11, bypass pipe 4-12;

[0077] Solvent monitoring system 5;

[0078] Detection rack 5-1, rack bottom plate 5-1-1, rack bottom plate through hole 5-1-1-1, rack side plate 5-1-2, rack back plate 5-1-3, rack cover plate 5-1-4, rack handle 5-1-5, three-way valve island 5-2, pipe priming valve island 5-3, pressure valve 5-4, pressure valve fixing block 5-4-1, photoelectric switch 5-5, diversion pipe 5-6, temperature sensor 5-7, first bracket 5-8, second bracket 5-9, third bracket 5-10, pipe clamp 5-11, pipe clamp slot 5-11-1, fourth bracket 5-12;

[0079] Solvent circulation system 6;

[0080] Solvent circulation pump 6-1, pulse valve 6-2, first solvent pipe 6-3, second solvent pipe 6-4, third solvent pipe 6-5, fourth solvent pipe 6-6, fifth solvent pipe 6-7;

[0081] Sampling system 7;

[0082] Sampling mechanism 7-1, sampling pipeline 7-2, sampling valve 7-3, sampling pump 7-4. Specific implementation mode

[0083] To make the technical solution of the present invention clearer and more definite, the present invention will be further described below with reference to the accompanying drawings. Any solution obtained by equivalent replacement of the technical features of the technical solution of the present invention and conventional reasoning falls within the protection scope of the present invention. The fixed connection, fixed setting, and fixed structure mentioned in this embodiment are all well-known technologies in the art such as gluing, welding, screw connection, bolt-nut connection, and riveting.

[0084] As can be seen from the accompanying drawings, a closed-loop sampling system for drug dissolution by the flow cell method includes a constant temperature water bath system 1, a flow cell system, a lifting mechanism 3, a circulating heating system 4, a solvent monitoring system 5, a solvent circulation system 6, and a sampling system 7;

[0085] The constant temperature water bath system 1 is used to keep the solvent in the solvent cups 1-4 warm; the constant temperature water bath system 1 includes a constant temperature water tank frame 1-1, a constant temperature water tank 1-2, a solvent cup rack 1-3, solvent cups 1-4 and solvent cup lids 1-5. The constant temperature water tank 1-2 is placed in the constant temperature water tank frame 1-1; the solvent cup rack 1-3 is arranged on the top surface of the constant temperature water tank 1-2; the solvent cups 1-4 are fitted into the solvent cup rack 1-3 to achieve limit fixation; the solvent cup lids 1-5 are buckled on the top surface of each solvent cup 1-4.

[0086] The flow cell system 2 is used for the process of the solvent flushing and dissolving the drug; the flow cell system 2 is arranged at the top of the constant temperature water bath system 1. The flow cell system 2 includes a flow cell frame 2-1, a flow cell 2-2 and a glass tube 2-3. The flow cell frame 2-1 is arranged on one side of the top surface of the solvent cup rack 1-3. The flow cell 2-2 is fixed on the flow cell frame 2-1 and is arranged in a horizontal array; the glass tube 2-3 is correspondingly sleeved on the outer wall of each flow cell 2-2; the solvent cup lid 1-5 is hoisted with the flow cell frame 2-1 through a clamping structure 2-4.

[0087] The lifting mechanism 3 is used for the overall lifting and lowering setting of the flow cell system 2; the lifting mechanism 3 is arranged on one side of the constant temperature water tank frame 1-1. The bottom end of the lifting mechanism 3 is fixed to the top surface of the constant temperature water tank frame 1-1, and one side of the top end of the lifting mechanism 3 is fixedly arranged with the side wall of the flow cell frame 2-1.

[0088] The circulating heating system 4 is used for the water circulation heat exchange of the solvent in the solvent cups 1-4 and the flow cell 2-2 to achieve temperature control; the circulating heating system 4 includes a heating device 4-1 and a water circulation pump 4-2. The heating device 4-1 is arranged on one side of the top surface of the solvent cup rack 1-3 and on one side of the flow cell frame 2-1; the constant temperature water tank 1-2 circulates water between the flow cell system 2 and the constant temperature water tank 1-2 through the water circulation pump 4-2 via a pipeline.

[0089] The solvent monitoring system 5 is used to monitor the temperature and pressure of the circulating solvent and to control the switching of the solvent circulation; the solvent monitoring system 5 is arranged on the top of the heating device 4-1. The circulation inlet end of the solvent monitoring system 5 is communicated with the heating device 4-1, and the circulation outlet end of the solvent monitoring system 5 is respectively communicated with the solvent cups 1-4 and the flow cell 2-2.

[0090] The solvent circulation system 6 is used to circulate the solvent among the constant temperature water bath system 1, the flow cell system 2, and the circulation heating system 4; the solvent circulation system 6 includes a solvent circulation pump 6-1 and a pulse valve 6-2. The output end of the solvent circulation pump 6-1 is connected to the input end of the pulse valve 6-2 through a pipeline. After the output end of the pulse valve 6-2 is connected to the circulation heating system 4, the flow cell system 2, and the constant temperature water bath system 1 in sequence through pipelines, it is connected to the input end of the solvent circulation pump 6-1.

[0091] The sampling system 7 is used to quantitatively sample the solvent in the solvent cup 1-4 at different times; the sampling system 7 includes a sampling mechanism 7-1, a sampling pipeline 7-2, a sampling valve 7-3, and a sampling pump 7-4. The sampling mechanism 7-1 is connected to the inside of the solvent cup 1-4 through the sampling pipeline 7-2. The sampling valve 7-3 is arranged on the sampling pipeline 7-2, and the sampling pump 7-4 is connected to the sampling pipeline 7-2.

[0092] Furthermore, the constant temperature water tank frame 1-1 includes a water tank bottom rod 1-1-1, a water tank bottom plate 1-1-2, water tank side plates 1-1-3, water tank frame feet 1-1-4, and a water tank back frame 1-1-5; the water tank bottom plate 1-1-2 is arranged on the top surface of the water tank bottom rod 1-1-1 and is arranged on both sides. One side of the water tank bottom plate 1-1-2 is turned up, and the other side of the water tank bottom plate 1-1-2 is turned down; the water tank side plates 1-1-3 are arranged on both sides of the water tank bottom plate 1-1-2 and are fixedly assembled with the water tank bottom plate 1-1-2 through fasteners. The tops of the water tank side plates 1-1-3 on both sides are fixedly assembled with the solvent cup holder 1-3 through fasteners; the water tank frame feet 1-1-4 are arranged at the bottom end of the water tank bottom rod 1-1-1; the water tank back frame 1-1-5 is arranged on one side of the water tank side plates 1-1-3.

[0093] Furthermore, the constant temperature water tank 1-2 is placed on the water tank bottom plate 1-1-2. The top side of the constant temperature water tank 1-2 is assembled with the solvent cup holder 1-3 through fasteners, and the side wall surface of the constant temperature water tank 1-2 is limited by the water tank side plates 1-1-3.

[0094] Further, the flow cell frame 2-1 includes side fixing blocks 2-1-1, a liquid collection tank 2-1-2, a drain pipe 2-1-3, cushion blocks 2-1-4, a liquid tank top plate 2-1-5, a water area base 2-1-6, a water area upper cover 2-1-7, a knob 2-1-8, support rods 2-1-9, side fixing plates 2-1-10, a mask connecting block 2-1-11, a mask fixing rod 2-1-12, a flow cell mask 2-1-13, and a flow cell back plate 2-1-14; the side fixing blocks 2-1-1 are arranged at both ends of the liquid collection tank 2-1-2, and the side fixing blocks 2-1-1 are assembled with the liquid collection tank 2-1-2 through fasteners; the cushion blocks 2-1-4 are arranged at the bottom sides of both ends of the liquid collection tank 2-1-2, and the cushion blocks 2-1-4 are assembled with the side fixing blocks 2-1-1 through fasteners; the side wall of the liquid collection tank 2-1-2 is provided with a side hole 2-1-2-1 of the liquid collection tank, and the bottom end of the liquid collection tank 2-1-2 is provided with a bottom hole 2-1-2-2 of the liquid collection tank. One end of the drain pipe 2-1-3 is assembled and communicated with the bottom hole 2-1-2-2 of the liquid collection tank. The bottom end of the drain pipe 2-1-3 penetrates through the solvent cup holder 1-3 and extends into the constant temperature water tank 1-2; the liquid tank top plate 2-1-5 is arranged on the top surface of the liquid collection tank 2-1-2, and the liquid tank top plate 2-1-5 is assembled with the liquid collection tank 2-1-2 through fasteners; the water area base 2-1-6 is fixed on the top surface of the liquid tank top plate 2-1-5 and is arranged in a horizontal array. A solvent inlet 2-1-6-1 is provided at the center of the water area base 2-1-6. One end of the solvent inlet 2-1-6-1 is connected with a solvent inlet joint 2-1-6-2. A water area water inlet 2-1-6-3 is provided on one side of the water area base 2-1-6, and the water area water inlet 2-1-6-3 is connected with a water area water inlet joint 2-1-6-4; the water area upper cover 2-1-7 is arranged on the top surface of the water area base 2-1-6. A upper cover fixing hole 2-1-7-1 is provided at the center of the water area upper cover 2-1-7. A water area water outlet 2-1-7-2 is provided on one side of the water area upper cover 2-1-7, and the water area water outlet 2-1-7-2 is connected with a water area water outlet joint 2-1-7-3; knob fixing cylinders 2-1-7-4 are provided on both sides of the top surface of the water area upper cover 2-1-7, and the knob 2-1-8 is inserted and connected with the knob fixing cylinders 2-1-7-4; the support rods 2-1-9 are arranged on both outer sides of the water area base 2-1-6. The bottom end of the support rod 2-1-9 is vertically fixed with the liquid tank top plate 2-1-5, and the top end of the support rod 2-1-9 is vertically fixed with the bottom surface of the water area upper cover 2-1-7; the side fixing plates 2-1-10 are arranged on both sides of the liquid tank top plate 2-1-5 and are symmetrically arranged. The bottom end of each side fixing plate 2-1-10 is fixed with the liquid tank top plate 2-1-5 through fasteners;The mask connection block 2-1-11 is arranged on the top side of each side fixing plate 2-1-10 and is assembled with the side fixing plate 2-1-10 through fasteners; both ends of the mask fixing rod 2-1-12 are rotatably arranged with the two side mask connection blocks 2-1-11 through rotating shafts; the flow cell mask 2-1-13 is attached to the side wall of the mask connection block 2-1-11, and the flow cell mask 2-1-13 is assembled with the mask fixing rod 2-1-12 through fasteners; the flow cell back plate 2-1-14 is arranged on one side of the flow cell 2-2, and both sides of the flow cell back plate 2-1-14 are assembled with the two side fixing plates 2-1-10 through fasteners.;

[0095] Further, the length of the cushion block 2-1-4 is longer than the width of the liquid collecting tank 2-1-2, and both ends of the cushion block 2-1-4 extend out of both sides of the bottom surface of the liquid collecting tank 2-1-2; rubber feet 2-1-4-1 are arranged on the bottom surface of each side of the cushion block 2-1-4, and the rubber feet 2-1-4-1 are fixed to both ends of the bottom surface of each cushion block 2-1-4 through insertion; the cushion block 2-1-4 is attached to the top surface of the solvent cup holder 1-3 through the rubber feet 2-1-4-1.

[0096] Further, the clamping structure 2-4 includes a hoisting plate 2-4-1, a hoisting rod 2-4-2 and a snap ring 2-4-3. The hoisting plate 2-4-1 is arranged on both sides of the liquid collecting tank 2-1-2. Each side of the hoisting plate 2-4-1 is attached to the top surface of the cushion block 2-1-4 and the side wall of the liquid collecting tank 2-1-2, and both ends of the hoisting plate 2-4-1 are fixed to the cushion block 2-1-4 through fasteners; the hoisting rod 2-4-2 is arranged at the top end of the solvent cup 1-4 rod, the hoisting rod 2-4-2 is vertically fixed to the solvent cup cover 1-5 through threads, a groove is formed in the circumferential direction at the top end of the hoisting rod 2-4-2 to form a hoisting rod top groove 2-4-2-1, the hoisting rod 2-4-2 penetrates through the hoisting plate 2-4-1, and the snap ring 2-4-3 is embedded in the hoisting rod top groove 2-4-2-1 to realize the hoisting setting of the solvent cup cover 1-5 and the hoisting plate 2-4-1.

[0097] Further, the number of liquid collecting tank bottom holes 2-1-2-2 provided in the liquid collecting tank 2-1-2 is two, and each drain pipe 2-1-3 is arranged in alignment with each liquid collecting tank bottom hole 2-1-2-2; the end of the drain pipe 2-1-3 is in a flange shape, one end of the drain pipe 2-1-3 extends into the liquid collecting tank bottom hole 2-1-2-2, the flange of the drain pipe 2-1-3 fits against the inner bottom surface of the liquid collecting tank 2-1-2, and the drain pipe 2-1-3 is vertically connected to the liquid collecting tank 2-1-2 through fasteners in cooperation with the liquid collecting tank 2-1-2.

[0098] Further, the top surface of the water area base 2-1-6 is in a stepped structure, forming a base step 2-1-6-5. A base sealing ring 2-1-6-6 is circumferentially fitted on the side wall of the base step 2-1-6-5. The bottom end of the glass tube 2-3 is sleeved on the outer wall of the base step 2-1-6-5 for plug-in fixation, and the glass tube 2-3 and the water area base 2-1-6 are sealed through the base sealing ring 2-1-6-6; the water area water inlet 2-1-6-3 penetrates through the top surface of the base step 2-1-6-5.

[0099] Further, the solvent inlet joint 2-1-6-2 is arranged at the center of the top surface of the water area base 2-1-6, and the solvent inlet joint 2-1-6-2 is vertically arranged with the water area base 2-1-6.

[0100] Further, the water area upper cover 2-1-7 is in a square structure; the center of the bottom surface of the water area upper cover 2-1-7 is in a stepped structure, forming an upper cover step 2-1-7-5. An upper cover sealing ring 2-1-7-6 is circumferentially fitted on the side wall of the upper cover step 2-1-7-5. The top end of the glass tube 2-3 is sleeved on the outer wall of the upper cover step 2-1-7-5 for plug-in fixation, and the glass tube 2-3 and the water area upper cover 2-1-7 are sealed through the upper cover sealing ring 2-1-7-6; the water area water outlet 2-1-7-2 penetrates through the bottom surface of the upper cover step 2-1-7-5.

[0101] Further, the solvent inlet joint 2-1-6-2, the water area water inlet joint 2-1-6-4, and the water area water outlet joint 2-1-7-3 all adopt Luer connectors.

[0102] Further, the bottom end of the knob 2-1-8 extends into the corresponding knob fixing cylinder 2-1-7-4, and the knob 2-1-8 is threadedly fixed to the knob fixing cylinder 2-1-7-4; a knob fixing piece 2-1-8-1 is provided on the side wall of each knob 2-1-8, and the knob fixing piece 2-1-8-1 is vertically arranged with the knob 2-1-8.

[0103] Further, the circulating heating system 4 further includes a water tank outlet pipe 4-3, a main water circulation pipe 4-4, a shunt tee 4-5, a shunt pipe 4-6, a return branch pipe 4-7, a make-up water tee 4-8, a make-up water pipe 4-9, a make-up water stop valve 4-10, a bypass tee 4-11 and a bypass pipe 4-12; one end of the water tank outlet pipe 4-3 communicates with the bottom end of the constant temperature water tank 1-2, and one end of the water tank outlet pipe 4-3 communicates with the suction end of the water circulation pump 4-2; one end of the main water circulation pipe 4-4 communicates with the output end of the water circulation pump 4-2, and one end of the main water circulation pipe 4-4 communicates with the shunt tee 4-5; one end of each shunt pipe 4-6 communicates with one end of the shunt tee 4-5, and the shunt pipe 4-6 is inserted into each water area inlet joint 2-1-6-4 through a manifold; both ends of each return branch pipe 4-7 are connected to a liquid collection tank side hole 2-1-2-1 and a water area outlet joint 2-1-7-3; the make-up water tee 4-8 is arranged on the water tank outlet pipe 4-3, the make-up water pipe 4-9 is connected to one end of the make-up water tee 4-8, and the make-up water stop valve 4-10 is arranged on the make-up water pipe 4-9; the bypass tee 4-11 is arranged on the main water circulation pipe 4-4, one end of the bypass pipe 4-12 communicates with the bypass tee 4-11, and one end of the bypass pipe 4-12 communicates with one side of the constant temperature water tank 1-2.

[0104] Further, the heating device 4-1 includes a heating fixing plate 4-1-1, heating wires 4-1-2, connecting heads 4-1-3, straight heads 4-1-4, connecting wires 4-1-5, a solvent inlet pipe 4-1-6, a solvent outlet pipe 4-1-7, and a heating shield 4-1-8; the heating fixing plate 4-1-1 is embedded in the top surface of the solvent cup holder 1-3; the heating wires 4-1-2 are arranged in the constant temperature water tank 1-2, and one end of each heating wire 4-1-2 penetrates through and extends out of the heating fixing plate 4-1-1 and is fixedly plugged with the connecting head 4-1-3; the connecting wires 4-1-5 are arranged on the top surface of the heating fixing plate 4-1-1, and both ends of the connecting wire 4-1-5 are fixedly plugged with the connecting head 4-1-3; the plug joints of the connecting wire 4-1-5 and the plug joints of the heating wires 4-1-2 are respectively threadedly fixed to both ends of the straight head 4-1-4 to connect the connecting wire 4-1-5 and the heating wires 4-1-2; the solvent inlet pipe 4-1-6 is arranged in the heating water tank, and one end of each solvent inlet pipe 4-1-6 penetrates through and extends out of the heating fixing plate 4-1-1 and is fixedly plugged with the connecting head 4-1-3; the solvent outlet pipe 4-1-7 is arranged in the heating water tank, and one end of each solvent outlet pipe 4-1-7 penetrates through and extends out of the heating fixing plate 4-1-1 and is fixedly plugged with the connecting head 4-1-3, and the bottom end of the solvent inlet pipe 4-1-6 is communicated with the bottom end of the solvent outlet pipe 4-1-7; the heating shield 4-1-8 is buckled on the top surface of the heating fixing plate 4-1-1, and one end of the heating shield 4-1-8 is rotatably connected to the constant temperature water tank frame 1-1 through a movable hinge.

[0105] Further, the heating wires 4-1-2 are arranged in two rows, each row of heating wires 4-1-2 is arranged in two layers, and each layer of heating wires 4-1-2 has a circular coiled pipe structure; two adjacent heating wires 4-1-2 connected by a single connecting wire 4-1-5 are arranged obliquely in the upper and lower layers.

[0106] Further, the connecting wire 4-1-5 has an inverted "U" shaped structure.

[0107] Further, the solvent inlet pipe 4-1-6 is arranged at the center of the top surface of the heating fixing plate 4-1-1 and between the heating wires 4-1-2; the solvent outlet pipe 4-1-7 is arranged on one side of the top surface of the heating fixing plate 4-1-1.

[0108] Further, the solvent monitoring system 5 includes a detection frame 5-1, a three-way valve island 5-2, a pipe flushing valve island 5-3, a pressure valve 5-4, a photoelectric switch 5-5, a diversion pipe 5-6, and a temperature sensor 5-7. The detection frame 5-1 is arranged on the top surface of the heating mask 4-1-8, and the detection frame 5-1 is fixedly arranged with the heating mask 4-1-8. The three-way valve island 5-2 is arranged at one end inside the detection frame 5-1, and the three-way valve island 5-2 is supported and fixed by a first bracket 5-8. The pipe flushing valve island 5-3 is arranged at one end inside the detection frame 5-1, and the pipe flushing valve island 5-3 is supported and fixed by a second bracket 5-9. The pressure valve 5-4 is arranged in the middle inside the detection frame 5-1 and on one side of the three-way valve island 5-2. A pressure valve fixing block 5-4-1 is arranged outside the pressure valve 5-4, and the pressure valve 5-4 is embedded in the pressure valve fixing block 5-4-1. The pressure valve fixing block 5-4-1 is fixedly supported by a third bracket 5-10. The photoelectric switch 5-5 is arranged at one end inside the detection frame 5-1 and on one side of the pressure valve 5-4. The photoelectric switch 5-5 is fixed in the detection frame 5-1 by a pipe clamp 5-11. The diversion pipe 5-6 is arranged at the top end inside the detection frame 5-1 and on one side of the pipe flushing valve island 5-3. The diversion pipe 5-6 is fixedly supported by a fourth bracket 5-12. The temperature sensor 5-7 is vertically fixed at the bottom end of the diversion pipe 5-6, and the end of the temperature sensor 5-7 extends into the inside of the diversion pipe 5-6. The solvent outlet pipe 4-1-7 extends into the detection frame 5-1 through a pipeline and is communicated with the inlet end of the corresponding three-way valve island 5-2. The side-end outlet of the three-way valve island 5-2 is communicated with one end of the corresponding pressure valve 5-4 through a pipeline. The other end of the pressure valve 5-4 is communicated with a pipeline, and the pipeline is embedded in the pipe clamp 5-11. The top-end outlet of the three-way valve island 5-2 is communicated with the bottom end of the corresponding pipe flushing valve island 5-3 through a pipeline. One end outlet of the pipe flushing valve island 5-3 is communicated with the input port of the solvent cup cover 1-5 through a pipeline. One end outlet of the pipe flushing valve island 5-3 is communicated with the corresponding diversion pipe 5-6 through a pipeline.

[0109] Further, the detection rack 5-1 includes a rack bottom plate 5-1-1, a rack side plate 5-1-2, a rack back plate 5-1-3, a rack cover plate 5-1-4 and a rack handle 5-1-5, the rack side plates 5-1-2 are symmetrically arranged on both sides, the top and bottom edges of the rack side plates 5-1-2 on each side are bent, the bottom sides of the rack side plates 5-1-2 on both sides are fixed to the top surface of the heating shield 4-1-8, the rack bottom plate 5-1-1 is arranged between the bottom sides of the rack side plates 5-1-2 on both sides, and is fixed to the rack side plates 5-1-2 on both sides, and the rack bottom plate 5-1-1 A rack bottom plate through hole 5-1-1-1 is provided on one side of the surface; the cross-section of the rack back panel 5-1-3 is a "匚"-shaped structure, and the rack back panel 5-1-3 is arranged at one end of the machine side panels on both sides, and the rack back panel 5-1-3 is fixed to the rack side panels 5-1-2 on both sides; the rack cover panel 5-1-4 is buckled on the top side of the rack side panels 5-1-2, and the two sides of the rack cover panel 5-1-4 are fixed to the top sides of the rack side panels 5-1-2 on both sides; the rack handle 5-1-5 is arranged on one side of the rack side panel 5-1-2 on one side, and is vertically fixed to the rack side panel 5-1-2.

[0110] Furthermore, the three-way valve island 5-2 is arranged at the top of the through hole 5-1-1-1 of the rack bottom plate; the first bracket 5-8 is arranged on one side of the three-way valve island 5-2, and the cross-section of the first bracket 5-8 is an "L"-shaped structure. The bottom surface of the first bracket 5-8 is fixed to the rack bottom plate 5-1-1, and the top side surface of the second bracket 5-9 is fixed to the side surface of the three-way valve island 5-2.

[0111] Furthermore, the lubricating valve island 5-3 is arranged at the top end of the three-way valve island 5-2; the second bracket 5-9 is arranged at both ends of the lubricating valve island 5-3, and the cross-section of the second bracket 5-9 at each end is an "L"-shaped structure, the bottom surface of the second bracket 5-9 at each end is fixed to the rack bottom plate 5-1-1, and the top side surface of the second bracket 5-9 at each end is fixed to the end surface of the lubricating valve island 5-3, and the lubricating valve island 5-3 and the three-way valve island 5-2 are arranged in the same direction.

[0112] Furthermore, the pressure valves 5-4 are arranged in a horizontal array, and each of the pressure valves 5-4 is arranged in opposition to the outlet of the three-way valve island 5-2; the third bracket 5-10 is arranged on the bottom side of the pressure valve 5-4, and the third bracket 5-10 is a "Z"-shaped structure. The bottom surface of the third bracket 5-10 is fixed to the frame bottom plate 5-1-1, and the top surface of the third bracket 5-10 is fixed to the pressure valve fixing block 5-4-1.

[0113] Further, the pipe clamps 5-11 are arranged in a horizontal array on the top surface of the frame bottom plate 5-1-1. The top surface of each pipe clamp 5-11 is in a groove shape, forming a pipe clamp card slot 5-11-1. Each pipe clamp card slot 5-11-1 is arranged in alignment with the pressure valve 5-4; the photoelectric switch 5-5 is arranged on the top surface of the pipe clamp 5-11 and straddles the top surface of the pipe clamp card slot 5-11-1.

[0114] Further, the diversion pipes 5-6 are arranged in a horizontal array. The diversion pipes 5-6 are arranged at the same height as the pipe wetting valve island 5-3. Each diversion pipe 5-6 is arranged in alignment with the outlet of the pipe wetting valve island 5-3; the fourth bracket 5-12 is arranged between the third bracket 5-10 and the pipe clamp 5-11. The cross section of the fourth bracket 5-12 is in a "C" shape. The bottom surface of the fourth bracket 5-12 is fixed to the frame bottom plate 5-1-1, and the diversion pipe 5-6 is arranged on the top surface of the fourth bracket 5-12.

[0115] Further, the solvent circulation system 6 further includes a first solvent pipe 6-3, a second solvent pipe 6-4, a third solvent pipe 6-5, a fourth solvent pipe 6-6, and a fifth solvent pipe 6-7; one end of the first solvent pipe 6-3 is communicated with the top end of the flow cell 2-2, and one end of the first solvent pipe 6-3 is communicated with the input port of the solvent cup cover 1-5; one end of the second solvent pipe 6-4 is communicated with the output port of the solvent cup cover 1-5, and one end of the second solvent pipe 6-4 is communicated with the suction end of the solvent circulation pump 6-1; one end of the third solvent pipe 6-5 is communicated with the output end of the solvent circulation pump 6-1, and one end of the third solvent pipe 6-5 is connected to the input end of the pulse valve 6-2; one end of the fourth solvent pipe 6-6 is communicated with the output end of the pulse valve 6-2, and one end of the fourth solvent pipe 6-6 is connected to the solvent inlet pipe 4-1-6; one end of the fifth solvent pipe 6-7 is connected to one end of the diversion pipe 5-6, and one end of the fifth solvent pipe 6-7 is connected to the solvent inlet 2-1-6-1 of the flow cell 2-2.

[0116] Further, the solvent circulation pump 6-1 adopts a piston injection pump; the number of the solvent circulation pumps 6-1 is two. One end of the second solvent pipe 6-4 is respectively connected to the suction ends of each solvent circulation pump 6-1 through a manifold, and one end of the third solvent pipe 6-5 is respectively connected to the output ends of each solvent circulation pump 6-1 through a manifold.

[0117] Further, the heating wire 4-1-2, the water circulation pump 4-2, the solvent circulation pump 6-1, the pulse valve 6-2, the sampling valve 7-3, the sampling pump 7-4, the three-way valve island 5-2, the pipe flushing valve island 5-3, the photoelectric switch 5-5, and the temperature sensor 5-7 are electrically connected to an external controller through wires; the controller controls the set temperature value of the heating wire 4-1-2, and the controller controls the opening and closing of the water circulation pump 4-2, the solvent circulation pump 6-1, the pulse valve 6-2, the sampling valve 7-3, the sampling pump 7-4, the three-way valve island 5-2, and the pipe flushing valve island 5-3. The photoelectric switch 5-5 uploads signals to the controller, and the temperature sensor 5-7 uploads temperature information to the controller.

[0118] A method for using a closed-loop sampling system for drug dissolution by the flow cell method is as follows:

[0119] 1. Support and fix the drug support structure in the flow cell 2-2, insert the flow cell 2-2 into the upper cover fixing hole 2-1-7-1, fix the bottom end of the flow cell 2-2 to the solvent inlet joint 2-1-6-2 by plugging, and then rotate the knob 2-1-8 so that the knob fixing piece 2-1-8-1 latches onto the end of the flow cell 2-2; connect one end of the flow cell 2-2 to one end of the first solvent pipe 6-3 to connect the flow cell 2-2 to the solvent circulation system 6.

[0120] 2. Start the adjustment and lifting mechanism 3, lower the lifting mechanism 3 to the lowest point, drive the flow cell system 2 to the lowest position by the lifting mechanism 3, and press the solvent cup cover 1-5 against the hole of the solvent cup 1-4.

[0121] 3. Start the heating operation of the heating wire 4-1-2, and the heating wire 4-1-2 heats the water in the constant temperature water tank 1-2.

[0122] 4. Start the water circulation pump 4-2. The water in the constant temperature water tank 1-2 is sucked into the suction end of the water circulation pump 4-2 through the water tank outlet pipe 4-3. Through the pumping action of the water circulation pump 4-2, the water flows into the shunt pipe 4-6 through the shunt three-way 4-5, and then through the manifold, it is input into the glass tube 2-3 through the water area inlet 2-1-6-3. After the glass tube 2-3 is filled, it is injected into the liquid collection tank 2-1-2 through the return branch pipe 4-7. The water in the liquid collection tank 2-1-2 is re-injected into the constant temperature water tank 1-2 through the drain pipe 2-1-3.

[0123] 5. Connect one outlet end of the priming valve island 5-3 to the input port of the solvent cup lid 1-5 directly through a conduit; start the solvent circulation pump 6-1. The solvent in the solvent cup 1-4 is sucked into the suction end of the solvent circulation pump 6-1 through the second solvent pipe 6-4. Through the pumping action of the solvent circulation pump 6-1, the solvent is sent to the pulse valve 6-2 through the third solvent pipe 6-5. The pulse valve 6-2 conducts pulse delivery of the solvent to simulate human blood circulation. The solvent enters the constant temperature water tank 1-2 through the fourth solvent pipe 6-6 for heat exchange. The solvent flows through the heating device 4-1 and the solvent monitoring system 5 and directly returns to the solvent cup 1-4; meanwhile, the solvent fills the diversion pipe 5-6 to monitor the temperature of the solvent.

[0124] 6. When the temperature sensor 5-7 monitors that the solvent temperature reaches 37°C, the output end of the diversion pipe 5-6 is connected to the solvent inlet 2-1-6-1 of the flow cell 2-2 through the fifth solvent pipe 6-7; the solvent flowing into the solvent monitoring system 5 passes through the priming valve island 5-3 and flows into the bottom of the flow cell 2-2 through the fifth solvent pipe 6-7. After the solvent flushes the drug, it is re-injected into the solvent cup 1-4 through the first solvent pipe 6-3.

[0125] 7. Start the sampling pump 7-4 and open the sampling valve 7-3. The solvent in the solvent cup 1-4 is sucked into the suction end of the sampling pump 7-4 through the sampling pipeline 7-2 and is sent to the sampling mechanism 7-1 through the pumping action of the sampling pump 7-4. The sampling mechanism 7-1 conducts time-sharing quantitative sampling.

[0126] The beneficial effects of the present invention are:

[0127] 1. The present invention designs a closed-loop flow cell method drug dissolution sampling system for drug dissolution. The invention sets the flow cell system above the constant temperature water area system and realizes the longitudinal lift between the flow cell system and the constant temperature water area system through a lifting mechanism. The two systems are integrally designed. One device can realize the drug dissolution of the flow cell and the function of circulating heat preservation of the water area, and integrally processes the system functions. On the premise of ensuring the functionality of the device, the structure of the device is compact, the overall volume of the device is reduced, and it is convenient for the placement and transportation of the device.

[0128] 2. On one side of the constant temperature water tank system of this device, a circulating heating system is integrally arranged. In the circulating heating system, the water area of the constant temperature water tank is heated. The heating device fixes the heating wire in the form of a heating fixing plate. The heating wires are arranged in an array in the constant temperature water tank, and multiple groups of heating wires are inserted into the constant temperature water tank to ensure good fixation of the heating wires. When the water circulates in the constant temperature water tank, there is no deviation of the heating wires, ensuring a good heating effect. At the same time, in this invention, the heating wires are designed as coil structures and are arranged in a staggered manner in the upper and lower layers, greatly reducing the structural size of the heating wires and increasing the heat exchange area between the heating wires and the water area. By connecting adjacent two heating wire structures with connecting wires, the heating wires are modularly arranged, further improving the heating effect of the heating wires. The heating wires cooperate with the water flow in the constant temperature water tank, and the temperature distribution in the water area is uniform, enabling precise temperature control of the water in the solvent cup at 37°C.

[0129] 3. In this invention, a solvent monitoring system is arranged at the heating device. Before heating and controlling the solvent to 37°C, the solvent is circulated and heated between the heating device and the solvent cup. When the solvent reaches 37°C, the solvent flows through the flow cell for drug dissolution circulation. By using a lubricating pipe valve island to switch the flow direction of the solvent, precise temperature control of the solvent can be achieved, and it is ensured that the solvent always operates at 37°C, realizing temperature control of the solvent. The solvent monitoring system can also monitor the circulating pressure of the solvent. Through the function of the three-way valve island, it can be detected that when the circulating pressure of the solvent is greater than 0.1 MPa, audible and visual alarms can be given to warn the experimental personnel, ensuring that the circulating pipeline of the solvent maintains a safe pressure circulation, and the safety performance of the device is high.

Claims

1. A closed-loop sampling system for drug dissolution by flow cell method, characterized in that, it includes a constant temperature water bath system (1), a flow cell system (2), a lifting mechanism (3), a circulating heating system (4), a solvent monitoring system (5), a solvent circulation system (6) and a sampling system (7); The constant temperature water bath system (1) is used for keeping the solvent in the solvent cup (1-4) warm; the constant temperature water bath system (1) includes a constant temperature water tank frame (1-1), a constant temperature water tank (1-2), a solvent cup holder (1-3), a solvent cup (1-4) and a solvent cup cover (1-5), the constant temperature water tank (1-2) is placed in the constant temperature water tank frame (1-1); the solvent cup holder (1-3) is arranged on the top surface of the constant temperature water tank (1-2); the solvent cup (1-4) is fitted into the solvent cup holder (1-3) to achieve limit fixation; the solvent cup cover (1-5) is buckled on the top surface of each solvent cup (1-4); The flow cell system (2) is used for the process of flushing and dissolving the drug with the solvent; the flow cell system (2) is arranged at the top of the constant temperature water bath system (1), the flow cell system (2) includes a flow cell frame (2-1), a flow cell (2-2) and a glass tube (2-3), the flow cell frame (2-1) is arranged on one side of the top surface of the solvent cup holder (1-3), the flow cell (2-2) is fixed on the flow cell frame (2-1) and is arranged in a horizontal array; the glass tube (2-3) is correspondingly sleeved on the outer wall of each flow cell (2-2); the solvent cup cover (1-5) is hoisted with the flow cell frame (2-1) through a clamping structure (2-4); The lifting mechanism (3) is used for the overall lifting and lowering setting of the flow cell system (2); the lifting mechanism (3) is arranged on one side of the constant temperature water tank frame (1-1), the bottom end of the lifting mechanism (3) is fixed to the top surface of the constant temperature water tank frame (1-1), and one side of the top end of the lifting mechanism (3) is fixedly arranged with the side wall of the flow cell frame (2-1); The circulating heating system (4) is used for the water circulation heat exchange of the solvent in the solvent cup (1-4) and the flow cell (2-2) to achieve temperature control; the circulating heating system (4) includes a heating device (4-1) and a water circulation pump (4-2), the heating device (4-1) is arranged on one side of the top surface of the solvent cup holder (1-3) and on one side of the flow cell frame (2-1); the constant temperature water tank (1-2) circulates water between the flow cell system (2) and the constant temperature water tank (1-2) through the water circulation pump (4-2) via a pipeline; The solvent monitoring system (5) is used for monitoring the temperature and pressure of the circulating solvent and for switching control of the solvent circulation; the solvent monitoring system (5) is arranged on the top of the heating device (4-1), the circulating inlet end of the solvent monitoring system (5) is communicated with the heating device (4-1), and the circulating outlet end of the solvent monitoring system (5) is respectively communicated with the solvent cup (1-4) and the flow cell (2-2); The solvent circulation system (6) is used to circulate the solvent among the constant temperature water bath system (1), the flow cell system (2), and the circulation heating system (4); the solvent circulation system (6) includes a solvent circulation pump (6-1) and a pulse valve (6-2), the output end of the solvent circulation pump (6-1) is connected to the input end of the pulse valve (6-2) through a pipeline, and the output end of the pulse valve (6-2) is connected to the input end of the solvent circulation pump (6-1) after being connected to the circulation heating system (4), the flow cell system (2), and the constant temperature water bath system (1) in sequence through pipelines. The sampling system (7) is used to perform time-sharing quantitative sampling on the solvent in the solvent cup (1-4); the sampling system (7) includes a sampling mechanism (7-1), a sampling pipeline (7-2), a sampling valve (7-3), and a sampling pump (7-4), the sampling mechanism (7-1) is connected to the inside of the solvent cup (1-4) through the sampling pipeline (7-2), the sampling valve (7-3) is arranged on the sampling pipeline (7-2), and the sampling pump (7-4) is connected to the sampling pipeline (7-2).

2. A flow cell method drug dissolution closed-loop sampling system according to claim 1, characterized in that the constant temperature water tank frame (1-1) includes a water tank bottom rod (1-1-1), a water tank bottom plate (1-1-2), water tank side plates (1-1-3), water tank frame feet (1-1-4), and a water tank back frame (1-1-5); the water tank bottom plate (1-1-2) is arranged on the top surface of the water tank bottom rod (1-1-1), and is arranged on both sides, one side of the water tank bottom plate (1-1-2) is turned up, and one side of the water tank bottom plate (1-1-2) is turned down; the water tank side plates (1-1-3) are arranged on both sides of the water tank bottom plate (1-1-2) and are fixedly assembled with the water tank bottom plate (1-1-2) through fasteners, and the tops of the water tank side plates (1-1-3) on both sides are fixedly assembled with the solvent cup holder (1-3) through fasteners; the water tank frame feet (1-1-4) are arranged at the bottom end of the water tank bottom rod (1-1-1); the water tank back frame (1-1-5) is arranged on one side of the water tank side plates (1-1-3).

3. A flow cell method drug dissolution closed-loop sampling system according to claim 1, characterized in that The flow cell frame (2-1) includes side fixing blocks (2-1-1), a liquid collecting tank (2-1-2), a drain pipe (2-1-3), cushion blocks (2-1-4), a liquid tank top plate (2-1-5), a water area base (2-1-6), a water area upper cover (2-1-7), a knob (2-1-8), a support rod (2-1-9), side fixing plates (2-1-10), a mask connecting block (2-1-11), a mask fixing rod (2-1-12), a flow cell mask (2-1-13) and a flow cell back plate (2-1-14); the side fixing blocks (2-1-1) are arranged at both ends of the liquid collecting tank (2-1-2), and the side fixing blocks (2-1-1) are assembled with the liquid collecting tank (2-1-2) through fasteners; the cushion blocks (2-1-4) are arranged at the bottom sides of both ends of the liquid collecting tank (2-1-2), and the cushion blocks (2-1-4) are assembled with the side fixing blocks (2-1-1) through fasteners; the side wall of the liquid collecting tank (2-1-2) is provided with a side hole (2-1-2-1) of the liquid collecting tank, the bottom end of the liquid collecting tank (2-1-2) is provided with a bottom hole (2-1-2-2) of the liquid collecting tank, one end of the drain pipe (2-1-3) is assembled and communicated with the bottom hole (2-1-2-2) of the liquid collecting tank, and the bottom end of the drain pipe (2-1-3) penetrates through the solvent cup holder (1-3) and extends into the constant temperature water tank (1-2); the liquid tank top plate (2-1-5) is arranged on the top surface of the liquid collecting tank (2-1-2), and the liquid tank top plate (2-1-5) is assembled with the liquid collecting tank (2-1-2) through fasteners; the water area base (2-1-6) is fixed on the top surface of the liquid tank top plate (2-1-5) and is arranged in a horizontal array, a solvent inlet (2-1-6-1) is arranged at the center of the water area base (2-1-6), one end of the solvent inlet (2-1-6-1) is connected with a solvent inlet joint (2-1-6-2), a water area water inlet (2-1-6-3) is arranged on one side of the water area base (2-1-6), and the water area water inlet (2-1-6-3) is connected with a water area water inlet joint (2-1-6-4); the water area upper cover (2-1-7) is arranged on the top surface of the water area base (2-1-6), a fixing hole (2-1-7-1) of the upper cover is arranged at the center of the water area upper cover (2-1-7), a water area water outlet (2-1-7-2) is arranged on one side of the water area upper cover (2-1-7), and the water area water outlet (2-1-7-2) is connected with a water area water outlet joint (2-1-7-3); fixing cylinders (2-1-7-4) of the knob are arranged on both sides of the top surface of the water area upper cover (2-1-7), and the knob (2-1-8) is inserted and connected with the fixing cylinders (2-1-7-4) of the knob;The support rods (2-1-9) are arranged on both outer sides of the water area base (2-1-6). The bottom ends of the support rods (2-1-9) are perpendicularly fixed to the liquid tank top plate (2-1-5), and the top ends of the support rods (2-1-9) are perpendicularly fixed to the bottom surface of the water area upper cover (2-1-7). The side fixing plates (2-1-10) are arranged on both sides of the liquid tank top plate (2-1-5) symmetrically. The bottom end of each side fixing plate (2-1-10) is fixed to the liquid tank top plate (2-1-5) through fasteners. The mask connecting blocks (2-1-11) are arranged on the top sides of each side fixing plate (2-1-10) and are assembled with the side fixing plates (2-1-10) through fasteners. Both ends of the mask fixing rod (2-1-12) are rotatably arranged with the mask connecting blocks (2-1-11) on both sides through rotating shafts. The flow cell mask (2-1-13) is attached to the side wall of the mask connecting block (2-1-11), and the flow cell mask (2-1-13) is assembled with the mask fixing rod (2-1-12) through fasteners. The flow cell back plate (2-1-14) is arranged on one side of the flow cell (2-2), and both sides of the flow cell back plate (2-1-14) are assembled with the side fixing plates (2-1-10) on both sides through fasteners. ; 4. A flow cell method drug dissolution closed-loop sampling system according to claim 3, characterized in that The clamping structure (2-4) includes a hoisting plate (2-4-1), a hoisting rod (2-4-2) and a clamping ring (2-4-3). The hoisting plate (2-4-1) is arranged on both sides of the liquid collecting tank (2-1-2). On each side, the hoisting plate (2-4-1) is arranged in contact with the top surface of the cushion block (2-1-4) and the side wall of the liquid collecting tank (2-1-2). Both ends of the hoisting plate (2-4-1) are fixed to the cushion block (2-1-4) through fasteners; the hoisting rod (2-4-2) is arranged at the top end of the rod of the solvent cup (1-4). The hoisting rod (2-4-2) is vertically fixed to the solvent cup cover (1-5) through threads. The top end of the hoisting rod (2-4-2) is circumferentially grooved to form a hoisting rod top groove (2-4-2-1). The hoisting rod (2-4-2) penetrates through the hoisting plate (2-4-1), and the clamping ring (2-4-3) is embedded in the hoisting rod top groove (2-4-2-1) to realize the hoisting arrangement of the solvent cup cover (1-5) and the hoisting plate (2-4-1).

5. A closed-loop sampling system for drug dissolution by flow cell method according to claim 3, characterized in that, The circulating heating system (4) further includes a water tank outlet pipe (4-3), a water circulation main pipe (4-4), a shunt tee (4-5), a shunt pipe (4-6), a return branch pipe (4-7), a water replenishing tee (4-8), a water replenishing pipe (4-9), a water replenishing stop valve (4-10), a branch tee (4-11) and a bypass pipe (4-12); one end of the water tank outlet pipe (4-3) is connected to the bottom end of the constant temperature water tank (1-2), and one end of the water tank outlet pipe (4-3) is connected to the suction end of the water circulation pump (4-2); one end of the water circulation main pipe (4-4) is connected to the output end of the water circulation pump (4-2), and one end of the water circulation main pipe (4-4) is connected to the shunt tee (4-5); one end of each shunt pipe (4-6) is connected to one end of the shunt tee (4-5), and the shunt pipe (4-6) is inserted into each water area inlet joint (2-1-6-4) through a manifold; both ends of each return branch pipe (4-7) are connected to a liquid collecting tank side hole (2-1-2-1) and a water area outlet joint (2-1-7-3); the water replenishing tee (4-8) is arranged on the water tank outlet pipe (4-3), the water replenishing pipe (4-9) is connected to one end of the water replenishing tee (4-8), and the water replenishing stop valve (4-10) is arranged on the water replenishing pipe (4-9); the branch tee (4-11) is arranged on the water circulation main pipe (4-4), one end of the bypass pipe (4-12) is communicated with the branch tee (4-11), and one end of the bypass pipe (4-12) is communicated with one side of the constant temperature water tank (1-2).

6. A closed-loop sampling system for drug dissolution by flow cell method according to claim 1, characterized in that, The heating device (4-1) includes a heating fixed plate (4-1-1), a heating wire (4-1-2), a connection head (4-1-3), a direct head (4-1-4), a connection wire (4-1-5), a solvent inlet pipe (4-1-6), a solvent outlet pipe (4-1-7), and a heating shield (4-1-8); the heating fixed plate (4-1-1) is embedded in the top surface of the solvent cup holder (1-3); the heating wire (4-1-2) is arranged in the constant temperature water tank (1-2), and one end of each heating wire (4-1-2) penetrates out of the heating fixed plate (4-1-1) and is fixedly inserted into the connection head (4-1-3); the connection wire (4-1-5) is arranged on the top surface of the heating fixed plate (4-1-1), and both ends of the connection wire (4-1-5) are fixedly inserted into the connection head (4-1-3); the insertion joints of the connection wire (4-1-5) and the insertion joints of the heating wire (4-1-2) are respectively thread-fixed to both ends of the direct head (4-1-4) to connect the connection wire (4-1-5) and the heating wire (4-1-2); the solvent inlet pipe (4-1-6) is arranged in the constant temperature water tank (1-2), and one end of each solvent inlet pipe (4-1-6) penetrates out of the heating fixed plate (4-1-1) and is fixedly inserted into the connection head (4-1-3); the solvent outlet pipe (4-1-7) is arranged in the constant temperature water tank, and one end of each solvent outlet pipe (4-1-7) penetrates out of the heating fixed plate (4-1-1) and is fixedly inserted into the connection head (4-1-3), and the bottom end of the solvent inlet pipe (4-1-6) is communicated with the bottom end of the solvent outlet pipe (4-1-7); the heating shield (4-1-8) is buckled on the top surface of the heating fixed plate (4-1-1), and one end of the heating shield (4-1-8) is rotatably connected to the constant temperature water tank frame (1-1) through a movable hinge.

7. A closed-loop sampling system for drug dissolution by flow cell method according to claim 6, characterized in that The solvent monitoring system (5) includes a detection rack (5-1), a three-way valve island (5-2), a pipe flushing valve island (5-3), a pressure valve (5-4), a photoelectric switch (5-5), a diversion pipe (5-6), and a temperature sensor (5-7); the detection rack (5-1) is arranged on the top surface of the heating shield (4-1-8), and the detection rack (5-1) is fixedly arranged with the heating shield (4-1-8); the three-way valve island (5-2) is arranged at one end inside the detection rack (5-1), and the three-way valve island (5-2) is supported and fixed by a first bracket (5-8); the pipe flushing valve island (5-3) is arranged at one end inside the detection rack (5-1), and the pipe flushing valve island (5-3) is supported and fixed by a second bracket (5-9); the pressure valve (5-4) is arranged in the middle inside the detection rack (5-1) and on one side of the three-way valve island (5-2), a pressure valve fixing block (5-4-1) is arranged outside the pressure valve (5-4), the pressure valve (5-4) is embedded in the pressure valve fixing block (5-4-1), and the pressure valve fixing block (5-4-1) is fixedly supported by a third bracket (5-10); the photoelectric switch (5-5) is arranged at one end inside the detection rack (5-1) and on one side of the pressure valve (5-4), and the photoelectric switch (5-5) is fixed in the detection rack (5-1) by a pipe clamp (5-11); the diversion pipe (5-6) is arranged at the top end inside the detection rack (5-1) and on one side of the pipe flushing valve island (5-3), and the diversion pipe (5-6) is fixedly supported by a fourth bracket (5-12); the temperature sensor (5-7) is vertically fixed at the bottom end of the diversion pipe (5-6), and the end of the temperature sensor (5-7) extends into the inside of the diversion pipe (5-6); the solvent outlet pipe (4-1-7) extends into the detection rack (5-1) through a pipe and is communicated with the inlet end of the corresponding three-way valve island (5-2); the side-end outlet of the three-way valve island (5-2) is communicated with one end of the corresponding pressure valve (5-4) through a pipe; the other end of the pressure valve (5-4) is communicated with a pipe, and the pipe is embedded in the pipe clamp (5-11); the top-end outlet of the three-way valve island (5-2) is communicated with the bottom end of the corresponding pipe flushing valve island (5-3) through a pipe; one end outlet of the pipe flushing valve island (5-3) is communicated with the input port of the solvent cup cover (1-5) through a pipe; one end outlet of the pipe flushing valve island (5-3) is communicated with the corresponding diversion pipe (5-6) through a pipe.

8. According to a closed-loop sampling system for drug dissolution by flow cell method as claimed in claim 7, characterized in that The detection rack (5-1) includes a rack bottom plate (5-1-1), rack side plates (5-1-2), a rack back plate (5-1-3), a rack cover plate (5-1-4) and a rack handle (5-1-5). The rack side plates (5-1-2) are symmetrically arranged on both sides. The top and bottom edges of each rack side plate (5-1-2) are bent. The bottom sides of the two rack side plates (5-1-2) are fixed to the top surface of the heating mask (4-1-8). The rack bottom plate (5-1-1) is arranged between the bottom sides of the two rack side plates (5-1-2) and is fixed to the two rack side plates (5-1-2). A rack bottom plate through hole (5-1-1-1) is provided on one side of the surface of the rack bottom plate (5-1-1). The cross section of the rack back plate (5-1-3) is in a "C" shape. The rack back plate (5-1-3) is arranged at one end of the two rack side plates. The rack back plate (5-1-3) is fixed to the two rack side plates (5-1-2). The rack cover plate (5-1-4) is buckled on the top side of the rack side plates (5-1-2). The two sides of the rack cover plate (5-1-4) are fixed to the top sides of the two rack side plates (5-1-2). The rack handle (5-1-5) is arranged on one side of one rack side plate (5-1-2) and is vertically fixed to the rack side plate (5-1-2).

9. A closed-loop sampling system for drug dissolution by flow-through cell method according to claim 7, characterized in that, the solvent circulation system (6) further includes a first solvent pipe (6-3), a second solvent pipe (6-4), a third solvent pipe (6-5), a fourth solvent pipe (6-6) and a fifth solvent pipe (6-7); one end of the first solvent pipe (6-3) is communicated with the top end of the flow-through cell (2-2), and one end of the first solvent pipe (6-3) is communicated with the input port of the solvent cup cover (1-5); one end of the second solvent pipe (6-4) is communicated with the output port of the solvent cup cover (1-5), and one end of the second solvent pipe (6-4) is communicated with the suction end of the solvent circulation pump (6-1); one end of the third solvent pipe (6-5) is communicated with the output end of the solvent circulation pump (6-1), and one end of the third solvent pipe (6-5) is connected to the input end of the pulse valve (6-2); one end of the fourth solvent pipe (6-6) is communicated with the output end of the pulse valve (6-2), and one end of the fourth solvent pipe (6-6) is connected to the solvent inlet pipe (4-1-6); one end of the fifth solvent pipe (6-7) is connected to one end of the diversion pipe (5-6), and one end of the fifth solvent pipe (6-7) is connected to the solvent inlet (2-1-6-1) of the flow-through cell (2-2).

10. A method for using a closed-loop sampling system for drug dissolution by flow-through cell method according to any one of claims 1-9, characterized in that, the steps are as follows: (1). Support and fix the drug support structure inside the flow cell (2-2), insert the flow cell (2-2) into the upper cover fixing hole (2-1-7-1), fix the bottom end of the flow cell (2-2) by plugging it into the solvent inlet joint (2-1-6-2), and then rotate the knob (2-1-8) so that the knob fixing piece (2-1-8-1) latches onto the end of the flow cell (2-2); Connect one end of the flow cell (2-2) to one end of the first solvent tube (6-3) to connect the flow cell (2-2) to the solvent circulation system (6); (2). Start the adjustment and lifting mechanism (3), lower the lifting mechanism (3) to the lowest point, the lifting mechanism (3) drives the flow cell system (2) to the lowest position, and the solvent cup cover (1-5) presses down and fits at the hole of the solvent cup (1-4); (3). Start heating the heating wire (4-1-2), and the heating wire (4-1-2) heats the water in the constant temperature water tank (1-2); (4). Start the water circulation pump (4-2), the water in the constant temperature water tank (1-2) is sucked into the suction end of the water circulation pump (4-2) through the water tank outlet pipe (4-3), through the pumping action of the water circulation pump (4-2), the water flows into the shunt pipe (4-6) through the shunt tee (4-5), and then through the manifold is input into the glass tube (2-3) through the water area inlet (2-1-6-3). After the glass tube (2-3) is filled, it is injected into the liquid collection tank (2-1-2) from the return branch pipe (4-7), and the water in the liquid collection tank (2-1-2) is re-injected into the constant temperature water tank (1-2) through the drain pipe (2-1-3); (5). Connect one outlet end of the priming valve island (5-3) directly to the input port of the solvent cup cover (1-5) through a conduit; Start the solvent circulation pump (6-1), the solvent in the solvent cup (1-4) is sucked into the suction end of the solvent circulation pump (6-1) through the second solvent tube (6-4), through the pumping action of the solvent circulation pump (6-1), the solvent is sent to the pulse valve (6-2) through the third solvent tube (6-5), the pulse valve (6-2) performs a pulsed delivery action on the solvent to simulate human blood circulation, the solvent enters the constant temperature water tank (1-2) through the fourth solvent tube (6-6) for heat exchange, the solvent flows through the heating device (4-1) and the solvent monitoring system (5), and the solvent directly returns to the solvent cup (1-4); At the same time, the solvent fills the diversion tube (5-6) to monitor the temperature of the solvent; (6). When the temperature sensor (5-7) monitors that the solvent temperature reaches 37 °C, the output end of the diversion tube (5-6) is connected to the solvent inlet (2-1-6-1) of the flow cell (2-2) through the fifth solvent tube (6-7); The solvent flowing into the solvent monitoring system (5) passes through the priming valve island (5-3), flows into the bottom end of the flow cell (2-2) through the fifth solvent tube (6-7), after the solvent flushes the drug, it is re-injected into the solvent cup (1-4) through the first solvent tube (6-3); (7). Start the sampling pump (7-4) and open the sampling valve (7-3). The solvent in the solvent cup (1-4) is inhaled into the suction end of the sampling pump (7-4) through the sampling pipeline (7-2), and is sent into the sampling mechanism (7-1) through the pumping action of the sampling pump (7-4). The sampling mechanism (7-1) performs time-sharing quantitative sampling.

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