CN112113800A

CN112113800A - Closed-loop sampling system for drug dissolution by flow cell method and use method

Info

Publication number: CN112113800A
Application number: CN202010907775.2A
Authority: CN
Inventors: 李定中; 雷浩; 宋水军
Original assignee: Lugen Shanghai International Trade Co ltd
Current assignee: Lugen Shanghai International Trade Co ltd
Priority date: 2020-09-02
Filing date: 2020-09-02
Publication date: 2020-12-22

Abstract

A flow cell method drug dissolution closed loop sampling system and a use method thereof comprise a flow constant temperature water area system, a flow cell system, a lifting mechanism, a circulation heating system, a solvent monitoring system, a solvent circulation system and a sampling system; the constant-temperature water area system comprises a constant-temperature water tank frame, a constant-temperature water tank, a solvent cup holder, a solvent cup and a solvent cup cover; the flow-through pond system is arranged at the top end of the constant-temperature water area system; the lifting mechanism is arranged on one side of the constant-temperature water tank frame; the circulating heating system comprises a heating device and a water circulating 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 cell; the solvent circulating system comprises a solvent circulating pump and a pulse valve; the sampling system comprises a sampling mechanism, a sampling pipeline, a sampling valve and a sampling pump. The device has the advantages of compact structure, high heating efficiency of the heating device, uniform temperature distribution of the water area, accurate temperature control of the water temperature and monitoring of the temperature and the pressure of the solvent.

Description

Closed-loop sampling system for drug dissolution by flow cell method and use method

Technical Field

The invention relates to the technical field of medical experimental equipment application, in particular to a closed-loop sampling system for drug dissolution by a flow cell method and a use method thereof.

Background

With the rapid development of pharmaceutical technology and the emergence of a large number of novel medicaments and the current requirement on the In Vivo and In Vitro Correlation (IVIVC) of a dissolution rate measurement method, the traditional dissolution rate measurement method (paddle method, basket method and the like) has new problems in the aspect of measurement of preparation quality, such as the measurement of trace amount of medicinal preparations, the formulation of novel medicaments such as patches, microspheres and the like, and how to solve the in vivo and in vitro correlation of quick-release preparations. As a novel dissolution concentration checking method, the flow cell method mainly depends on flowing solvent to continuously flush the preparation, can well simulate the in vivo circulation of the medicine in a human body, and selects proper cell body accessories to be suitable for tablets, capsules, patches, microspheres, suppositories, suspensions, stents, implants, liposomes and the like.

In a drug dissolution test in which the drug dissolution concentration is low and the dissolution rate is slow, the drug dissolution amount is cumulatively changed with time, and a closed-loop dissolution test using a flow cell method is required. In the existing closed loop test process, after the medicine is dissolved out by flushing solvent in a flow cell, the solvent circulates into a solvent cup, the solvent cup is heated in a separate water area to keep the solvent close to the actual temperature of a human body, and then the solvent in the solvent cup is sampled by a sampling system in a timed, quantitative and fractional manner.

The prior flow cell method drug dissolution sampling system has the following defects:

1. when the temperature of the solvent in the solvent cup is controlled, an independent heating water tank is adopted to heat the water area of the solvent cup, the water area heating system and the dissolution system of the flow cell adopt two sets of devices, in the process of testing the system, an inlet and outlet pipeline of the solvent cup and an inlet and outlet of the dissolution system of the flow cell need to be spliced and fixed, and meanwhile, an inlet and outlet pipeline of circulating water of the heating system and a circulating water inlet and outlet pipeline of the dissolution system of the flow cell need to be spliced and fixed, so the test operation process is very inconvenient; and the whole equipment with the structure form occupies a large area, and the structure form is not compact enough.

2. When the water area of the solvent cup is heated, the heating wire is directly placed in the heating water tank of the solvent cup to directly and locally heat the water area in the water tank, so that the temperature distribution in the water tank is uneven, and the heat exchange temperature of the solvent in the water area and the solvent cup is difficult to control; and in the process of circulating the solvent, the solvent cannot be subjected to multipoint continuous temperature control, so that the solvent and the medicament are ensured to be at the optimal proper temperature for carrying out a medicament dissolution test.

Disclosure of Invention

In order to solve the existing problems, the invention discloses a closed-loop sampling system for drug dissolution by a flow cell method, which has the following specific technical scheme: a closed-loop sampling system for drug dissolution by a flow cell method comprises a flow constant-temperature water area system, a flow cell system, a lifting mechanism, a circulation heating system, a solvent monitoring system, a solvent circulation system and a sampling system;

the constant-temperature water area system is used for preserving the heat of the solvent in the solvent cup; the constant-temperature water area system comprises a constant-temperature water tank rack, a constant-temperature water tank, a solvent cup holder, a solvent cup and a solvent cup cover, wherein the constant-temperature water tank is placed in the constant-temperature water tank rack; the solvent cup holder is arranged on the top surface of the constant-temperature water tank; the solvent cup is embedded in the solvent cup holder to realize limiting and fixing; the solvent cup covers are buckled on the top surface of each solvent cup;

the flow cell system is used for the solvent to carry out the scouring and dissolving process on the medicine; the circulating pool system is arranged at the top end of the constant-temperature water area system and comprises a circulating pool rack, a circulating pool and a glass tube, wherein the circulating pool rack is arranged on one side of the top surface of the solvent cup holder, and the circulating pool is fixed on the circulating pool rack and arranged in a transverse array; the glass tubes are correspondingly sleeved on the outer wall of each flow cell; the solvent cup cover is hoisted with the flow cell frame through a clamping structure;

the lifting mechanism is used for carrying out integral lifting setting on the flow 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 with 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 cell frame;

the circulation heating system is used for carrying out water circulation heat exchange on the solvent in the solvent cup and the flow cell to realize temperature control; the circulation heating system comprises a heating device and a water circulation pump, wherein the heating device is arranged on one side of the top surface of the solvent cup holder and is arranged on one side of the circulating pool rack; the constant-temperature water tank circulates water between the circulating pool system and the constant-temperature water tank through a water circulating pump and a pipeline;

the solvent monitoring system is used for monitoring the temperature and the pressure of the circulating solvent and switching and controlling the circulation of the solvent; the solvent monitoring system is arranged at the top end of the heating device, 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 cell;

the solvent circulating system is used for circulating the solvent among the constant-temperature water area system, the circulating pool system and the circulating heating system; the solvent circulating system comprises a solvent circulating pump and a pulse valve, the output end of the solvent circulating pump is connected with the input end of the pulse valve through a pipeline, and the output end of the pulse valve is communicated through a pipeline and is sequentially connected to the circulating heating system, the circulating pool system and the constant-temperature water area system and then connected to the input end of the solvent circulating pump;

the sampling system is used for sampling the menstruum in the menstruum cup in a time-sharing and quantitative manner; the sampling system comprises a sampling mechanism, a sampling pipeline, a sampling valve and a sampling pump, wherein the sampling mechanism is connected into the solvent cup through the sampling pipeline, the sampling valve is arranged on the sampling pipeline, and the sampling pump is communicated with the sampling pipeline.

Further, the constant-temperature water tank rack comprises a water tank bottom rod, a water tank bottom plate, a water tank side plate, a water tank rack bottom foot 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 two sides, one side of the water tank bottom plate is in an upward folding shape, and the other side of the water tank bottom plate is in a downward folding shape; the water tank side plates are arranged on two sides of the water tank bottom plate and fixedly assembled with the water tank bottom plate through fasteners, and the top ends of the water tank side plates on the two sides are fixedly assembled with the solvent cup holder through fasteners; the bottom of the water tank frame is 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.

Furthermore, the constant temperature water tank is placed on the water tank bottom plate, the side edge of the top surface of the constant temperature water tank is assembled with the solvent cup holder through a fastener, and the side wall surface of the constant temperature water tank is limited through a water tank side plate.

Further, the flow cell frame comprises a side fixing block, a liquid collecting tank, a liquid discharge pipe, a cushion block, a liquid tank top plate, a water area base, a water area upper cover, a knob, a supporting rod, a side fixing plate, a cover connecting block, a cover fixing rod, a flow cell cover and a flow cell back plate; the side fixing blocks are arranged at two ends of the liquid collecting tank and are assembled with the liquid collecting tank through fasteners; the cushion blocks are arranged at the bottom sides of the two ends of the liquid collecting tank and are assembled with the side fixing blocks through fasteners; a liquid collecting groove side hole is formed in the side wall of the liquid collecting groove, a liquid collecting groove bottom hole is formed in the bottom end of the liquid collecting groove, one end of the liquid discharge pipe is communicated with the liquid collecting groove bottom hole in an assembling mode, and the bottom end of the liquid discharge 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 is assembled with the liquid collecting tank through a fastener; the water area base is fixed on the top surface of the liquid tank top plate and arranged in a transverse array, a solvent inlet is formed in the center of the water area base, one end of the solvent inlet is connected with a solvent inlet connector, a water area water inlet is formed in one side of the water area base, and the water area water inlet is connected with a water area water inlet connector; the water area upper cover is arranged on the top surface of the water area base, an upper cover fixing hole is formed in the center of the water area upper cover, a water area water outlet is formed in one side of the water area upper cover, and the water area water outlet is connected with a water area water outlet connector; knob fixing cylinders are arranged on two sides of the top surface of the water area upper cover, and the knobs are connected with the knob fixing cylinders in an inserting mode; the supporting rods are arranged on two sides of the outer wall of the water area base, the bottom ends of the supporting rods are vertically fixed with the liquid tank top plate, and the top ends of the supporting rods are vertically fixed with the bottom surface of the water area upper cover; the side fixing plates are arranged on two sides of the liquid tank top plate and are symmetrically arranged, and the bottom end of each side fixing plate is fixed with the liquid tank top plate through a fastening piece; the shade connecting block is arranged on the top side of the side fixing plate on each side and is assembled with the side fixing plate through a fastener; the two ends of the shade fixing rod are rotatably arranged with the shade connecting blocks on the two sides through a rotating shaft; the flow cell shade is attached to the side wall of the shade connecting block, and the flow cell shade is assembled with the shade fixing rod through a fastener; the flow cell back plate is arranged on one side of the flow cell, and the two sides of the flow cell back plate are assembled with the side fixing plates through fasteners.

Furthermore, the length of the cushion block is longer than the width of the liquid collecting groove, and two ends of the cushion block extend out of two sides of the bottom surface of the liquid collecting groove; rubber feet are arranged on the bottom surface of each cushion block on each side, and the rubber feet are fixed with the two 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 a rubber foot.

Furthermore, the clamping structure comprises hoisting plates, hoisting rods and clamping rings, the hoisting plates are arranged on two sides of the liquid collecting tank, the hoisting plates on each side are attached to the top surfaces of the cushion blocks and the side walls of the liquid collecting tank, and two ends of each hoisting plate are fixed to the cushion blocks through fasteners; the utility model discloses a solvent cup, including the menstruum cup pole, hoisting rod, rand embedding, hoisting rod set up in the top of menstruum cup pole, the hoisting rod with the menstruum bowl cover passes through screw thread vertical fixation, the top circumference of hoisting rod is the recess form, forms the hoisting rod top groove, the hoisting rod runs through the hoisting plate, the rand embedding in the hoisting rod top groove, realize the menstruum cup cover with the hoisting plate is the hoist and mount setting.

Furthermore, the number of the bottom holes of the liquid collecting tank arranged in the liquid collecting tank is two, and each liquid discharge pipe is arranged in an alignment mode with each bottom hole of the liquid collecting tank; the end part of the liquid discharge pipe is in a flange shape, one end of the liquid discharge pipe extends into the bottom hole of the liquid collecting tank, the flange of the liquid discharge pipe is attached to the inner bottom surface of the liquid collecting tank, and the liquid discharge pipe is matched with the liquid collecting tank through a fastener, so that the liquid discharge pipe is vertically communicated with the liquid collecting tank.

Furthermore, the top surface of the water area base is of a layered structure to form a base layered platform, a base sealing ring is embedded in the circumferential direction of the side wall of the base layered platform, the bottom end of the glass tube is sleeved on the outer wall of the base layered platform to realize insertion and fixation, and the glass tube and the water area base are sealed through the base sealing ring; the water inlet of the water area is communicated with the top surface of the base layer platform.

Furthermore, the solvent inlet joint is arranged at the center of the top surface of the water area base, and the solvent inlet joint and the water area base are vertically arranged.

Furthermore, the water area upper cover is of a square structure; the center of the bottom surface of the water area upper cover is of a layered platform-shaped structure to form an upper cover layer platform, an upper cover sealing ring is embedded in the circumferential direction of the side wall of the upper cover layer platform, the top end of the glass tube is sleeved on the outer wall of the upper cover layer platform to realize insertion and fixation, and the glass tube and the water area upper cover are sealed through the upper cover sealing ring; the water area water outlet is communicated with the bottom surface of the upper cover layer platform.

Furthermore, the solvent inlet joint, the water inlet joint and the water outlet joint are luer joints.

Furthermore, the bottom end of the knob extends into the knob fixing cylinder correspondingly, and the knob fixing cylinder are fixed in a threaded manner; each side wall of the knob is provided with a knob fixing sheet, and the knob fixing sheets are perpendicular to the knob.

Furthermore, the circulating heating system also comprises a water tank water outlet pipe, a water circulating main pipe, a flow dividing tee joint, a flow dividing pipe, a backflow branch pipe, a water supplementing tee joint, a water supplementing pipe, a water supplementing stop valve, a side branch tee joint and a bypass pipe; one end of the water tank water outlet pipe is communicated with the bottom end of the constant-temperature water tank, and one end of the water tank water outlet pipe is communicated with the suction end of the water circulating pump; one end of the water circulation main pipe is communicated with the output end of the water circulation pump, and one end of the water circulation main pipe is communicated with the flow dividing tee; one end of each flow dividing pipe is communicated with one end of each flow dividing tee, and each flow dividing pipe is inserted into each water area water inlet joint through a manifold; two ends of each backflow branch pipe are connected to one liquid collecting groove side hole and one water area water outlet connector; the water replenishing tee joint is arranged on the water outlet pipe of the water tank, the water replenishing pipe is connected to one end of the water replenishing tee joint, and the water replenishing stop valve is arranged on the water replenishing pipe; the bypass pipe is arranged on the water circulation main pipe, one end of the bypass pipe is communicated with the bypass pipe, and one end of the bypass pipe is communicated with one side of the constant temperature water tank.

Further, the heating device comprises a heating fixing plate, a heating wire, a connector, a straight connector, a connecting wire, a solvent inlet pipe, a solvent outlet pipe and a heating shade; 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 extends out of the heating fixing plate, and is fixedly inserted into the connector; the connecting wire is arranged on the top surface of the heating fixing plate, and two ends of the connecting wire are fixedly inserted through connectors; the plug-in connector of the connecting wire and the plug-in connector of the heating wire are respectively in threaded fixation with two ends of the straight connector, so that the connecting wire is connected with the heating wire; the solvent inlet pipes are arranged in the heating water tank, and one end of each solvent inlet pipe penetrates through the heating fixing plate and extends out of the heating fixing plate, and is fixedly connected with the connectors in an inserted manner; the solvent outlet pipes are arranged in the heating water tank, one end of each solvent outlet pipe penetrates through the heating fixing plate and extends out of the heating fixing plate, and is fixedly connected with the connectors in an inserting mode, and the bottom ends of the solvent inlet pipes are communicated with the bottom ends of the solvent outlet pipes; the heating shade is buckled on the top surface of the heating fixing plate, and one end of the heating shade is rotated with the constant-temperature water tank rack through a movable hinge.

Further, the heating wires are arranged in two rows, each row of the heating wires is arranged in two layers, and each layer of the heating wires is in a circular coil-shaped structure; two adjacent heating wires connected by the single connecting wire are arranged in an upper-layer and lower-layer inclined mode.

Furthermore, the connecting wire is of an inverted U-shaped structure.

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

Furthermore, the solvent monitoring system comprises a detection frame, a three-way valve island, a tube moistening valve island, a pressure valve, a photoelectric switch, a flow guide tube and a temperature sensor; the detection rack is arranged on the top surface of the heating shade and is fixedly arranged with the heating shade; the three-way valve island is arranged at one end in the detection rack and is supported and fixed through a first support; the tube lubricating valve island is arranged at one end of the interior of the detection rack and is supported and fixed through a second support; the pressure valve is arranged at the middle end in the detection rack and is arranged on one side of the three-way valve island, a pressure valve fixing block is arranged on the outer side of the pressure valve, the pressure valve is embedded into the pressure valve fixing block, and the pressure valve fixing block is fixedly supported through a third support; the photoelectric switch is arranged at one end in the detection rack and is arranged on one side of the pressure valve, and the photoelectric switch is fixed in the detection rack through a pipe clamp; the guide pipe is arranged at the top end inside the detection rack and is arranged on one side of the tube moistening valve island, and the guide pipe is fixedly supported through a fourth support; the temperature sensor is vertically fixed at the bottom end of the flow guide pipe, and the end part of the temperature sensor extends into the flow guide pipe; the solvent outlet pipe extends into the detection rack through a pipeline and is communicated with the inlet end corresponding to the three-way valve island; the side end outlet of the three-way valve island is communicated with one end corresponding to the pressure valve through a pipeline; the other end of the pressure valve is communicated with a pipeline, and the pipeline is embedded into the pipe clamp; the top outlet of the three-way valve island is communicated with the bottom end of the corresponding tube moistening valve island through a pipeline; an outlet at one end of the lubricating tube valve island is communicated with an input port of the solvent cup cover through a pipeline; and an outlet at one end of the tube moistening valve island is communicated with the corresponding flow guide tube through a pipeline.

Furthermore, the detection rack comprises a rack bottom plate, rack side plates, a rack back plate, a rack cover plate and a rack handle, wherein the rack side plates are symmetrically arranged on two sides, the top edge and the bottom edge of each rack side plate are bent, the bottom sides of the rack side plates on the two sides are fixed with the top surface of the heating shade, the rack bottom plate is arranged between the bottom sides of the rack side plates on the two sides and fixed with the rack side plates on the two sides, and a rack bottom plate through hole is formed in one side of the surface of the rack bottom plate; the section of the rack back plate is of a T-shaped structure, the rack back plate is arranged at one end of the rack side plates at two sides, and the rack back plate and the rack side plates at two sides are fixed; the machine frame cover plate is buckled on the top sides of the machine frame side plates, and two sides of the machine frame cover plate are fixed with the top sides of the machine frame side plates on two sides; the rack handle is arranged on one side of the rack side plate and is vertically fixed with the rack side plate.

Furthermore, the three-way valve island is arranged at the top end of the through hole of the bottom plate of the rack in an aligning way; the first support is arranged on one side of the three-way valve island, the cross section of the first support is of an L-shaped structure, the bottom surface of the first support is fixed with the bottom plate of the rack, and the top side surface of the second support is fixed with the side surface of the three-way valve island.

Further, the tube moistening valve island is oppositely arranged at the top end of the three-way valve island; the second supports are arranged at two ends of the tube moistening valve island, the section of each second support is of an L-shaped structure, the bottom surface of each second support is fixed with the bottom plate of the frame, the top side surface of each second support is fixed with the end surface of the tube moistening valve island, and the tube moistening valve island and the three-way valve island are arranged in the same direction.

Furthermore, the pressure valves are arranged in a transverse array, and each pressure valve is arranged in a contraposition with the outlet of the three-way valve island; the third support is arranged on the bottom side of the pressure valve and is of a Z-shaped structure, the bottom surface of the third support is fixed with the rack bottom plate, and the top surface of the third support is fixed with the pressure valve fixing block.

Furthermore, the pipe clamps are transversely arranged on the top surface of the bottom plate of the rack in an array mode, the top surface of each pipe clamp is in a groove shape to form a pipe clamp clamping groove, and each pipe clamp clamping groove is arranged in an alignment mode with the pressure valve; the photoelectric switch is arranged on the top surface of the pipe clamp and stretches across the top surface of the clamping groove of the pipe clamp.

Furthermore, the flow guide pipes are arranged in a transverse array, the flow guide pipes and the tube moistening valve island are arranged at the same height, and each flow guide pipe and the outlet of the tube moistening valve island are arranged in an alignment manner; the fourth support set up in between the third support with the pipe clamp, the cross-section of fourth support is "T" type structure, the bottom surface of fourth support with the frame bottom plate is realized fixedly, the honeycomb duct set up in the top surface of fourth support.

Further, the solvent circulating system further comprises 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 pipe is communicated with the top end of the flow cell, and one end of the first solvent pipe is communicated with the input port of the solvent cup cover; one end of the second solvent pipe is communicated with the output port of the solvent cup cover, and one end of the second solvent pipe is communicated with the suction end of the solvent circulating pump; one end of the third solvent pipe is communicated with the output end of the solvent circulating pump, and one end of the third solvent pipe is connected with the input end of the pulse valve; one end of the fourth solvent pipe is communicated with the output end of the pulse valve, and one end of the fourth solvent pipe is connected to the solvent inlet pipe; one end of the fifth solvent pipe is connected to one end of the flow guide pipe, and one end of the fifth solvent pipe is connected to the solvent inlet of the flow cell.

Further, the solvent circulating pump adopts a piston injection pump; the solvent circulating pumps are two in number, one end of the second solvent pipe is connected with the suction end of each solvent circulating pump through a manifold respectively, and one end of the third solvent pipe is connected with the output end of each solvent circulating pump through a manifold respectively.

Furthermore, the heating wire, the water circulating pump, the solvent circulating pump, the pulse valve, the sampling pump, the three-way valve island, the moistening pipe valve island, the photoelectric switch and the temperature sensor are electrically connected with an external controller through wires; the controller controls the set temperature value of the heating wire, the controller controls the opening and closing of the water circulating pump, the solvent circulating pump, the pulse valve, the sampling pump, the three-way valve island and the tube moistening valve island, the photoelectric switch uploads signals to the controller, and the temperature sensor uploads temperature information to the controller.

A use method of a closed-loop sampling system for drug dissolution by a flow cell method comprises the following steps:

1. the drug supporting structure is supported and fixed in the flow cell, the flow cell is inserted in the upper cover fixing hole, the bottom end of the flow cell is fixedly inserted with the solvent inlet connector, and then the knob is rotated to enable the knob fixing piece to be buckled at the end part of the flow cell; one end of the flow cell is communicated with one end of the first solvent pipe to realize that the flow cell is connected into the solvent circulating system;

2. starting the adjusting lifting mechanism, lowering the lifting mechanism to the lowest point, driving the flow cell system to descend to the lowest point position by the lifting mechanism, and pressing and attaching the solvent cup cover to the solvent cup hole;

3. starting heating work of the heating wires, wherein the heating wires heat water in the constant-temperature water tank;

4. starting a water circulating pump, sucking water in the constant-temperature water tank into a suction end of the water circulating pump through a water tank water outlet pipe, enabling the water to flow into a flow dividing pipe through a flow dividing tee under the pumping action of the water circulating pump, respectively inputting the water into a glass pipe through a water inlet of a water area through a manifold, injecting the glass pipe into a liquid collecting tank from a backflow branch pipe after the glass pipe is full, and re-injecting the water in the liquid collecting tank into the constant-temperature water tank through a liquid discharge pipe;

5. directly communicating one outlet end of the tube moistening valve island with an input port of the solvent cup cover through a conduit; the solvent circulating pump is started, the solvent in the solvent cup is sucked into the suction end of the solvent circulating pump through the second solvent pipe, the solvent is conveyed to the pulse valve through the third solvent pipe under the pumping action of the solvent circulating pump, the pulse valve performs pulse conveying action on the solvent to simulate blood circulation of a human body, the solvent enters the constant-temperature water tank through the fourth solvent pipe to exchange heat, the solvent flows through the heating device and the solvent monitoring system, and the solvent directly flows back into the solvent cup; meanwhile, the solvent is filled in the guide pipe, and the temperature of the solvent is monitored;

6. when the temperature sensor monitors that the temperature of the solvent reaches 37 ℃, the output end of the flow guide pipe is communicated with the solvent inlet of the flow cell through a fifth solvent pipe; the solvent flowing into the solvent monitoring system flows into the bottom end of the flow cell through the wetting tube valve island and the fifth solvent tube, and is flushed with the drug and then re-injected into the solvent cup through the first solvent tube;

7. the sampling pump is started and the sampling valve is opened, the solvent in the solvent cup is sucked into the suction end of the sampling pump through the sampling pipeline and is sent to the sampling mechanism through the pumping action of the sampling pump, and the sampling mechanism performs time-sharing quantitative sampling.

The invention has the beneficial effects that:

1. the invention presents a set of closed loop type flow cell method drug dissolution sampling system for drug dissolution design, the invention arranges the flow cell system above the constant temperature water area system, realizes the longitudinal lifting between the flow cell system and the constant temperature water area system through the lifting mechanism, integrates the two systems, realizes the drug dissolution of the flow cell and the circulating heat preservation function of the water area through one device, integrates the system function, ensures the functionality of the device, has compact structure, reduces the integral volume of the device, and is convenient for the device to be placed and transported.

2. The device is characterized in that a circulating heating system is integrally arranged on one side of a constant-temperature water tank system, the constant-temperature water tank is heated in a water area in the circulating heating system, a heating device adopts a heating fixing plate to fix heating wires, the heating wires are arranged in the constant-temperature water tank in an array mode, a plurality of groups of heating wires are inserted into the constant-temperature water tank in a cuttage mode, the heating wires are well fixed, and the heating wires are not deviated when water flows in the constant-temperature water tank in a circulating mode, so that a good heating effect is guaranteed; meanwhile, the heating wires are designed into the coil pipe structure and are arranged in a staggered manner from top to bottom, so that the structural size of the heating wires is greatly reduced, the heat exchange area between the heating wires and a water area is increased, the adjacent two heating wire structures are connected through connecting wires, the heating wires are arranged in a modularized manner, and the heating effect of the heating wires is further improved; the heater strip is matched with the water area in the constant temperature water tank to flow, the temperature in the water area is uniformly distributed, and the temperature of the water area in the solvent cup can be accurately controlled at 37 ℃.

3. The solvent monitoring system is arranged at the heating device, the solvent is heated between the heating device and the solvent cup before being controlled at 37 ℃, when the temperature of the solvent reaches 37 ℃, the solvent flows through the flow cell to perform drug dissolution circulation, and the flow direction of the solvent using the tube-wetting island is switched, so that the accurate temperature control of the solvent can be realized, the solvent is ensured to be always operated at 37 ℃, and the temperature control of the solvent is realized; the menstruum monitoring system can monitor the circulating pressure of the menstruum at the same time, and can carry out acousto-optic alarm after the circulating pressure of the menstruum is greater than 0.1MPa through the action of the three-way valve island, warn testers, ensure that a circulating pipeline of the menstruum keeps safe pressure circulation, and the device has high safety performance.

Drawings

Fig. 1 is a schematic diagram of the overall apparatus structure of the present invention.

Fig. 2 is a schematic structural view of the constant temperature water area system of the present invention.

Fig. 3 is a schematic structural outline of the flow cell system of the present invention.

Fig. 4 is a schematic view of a clamping arrangement of a flow cell system according to the invention.

FIG. 5 is a schematic view of the structure of the cap of the solvent cup of the present invention.

Fig. 6 is a schematic view of the internal structure of the flow cell system of the present invention.

Fig. 7 is a front view of a flow cell system of the present invention.

Fig. 8 is a front cross-sectional view of a flow cell system of the present invention.

Fig. 9 is a schematic cross-sectional view at a flow cell of the present invention.

Fig. 10 is a front view of the heating device and vehicle monitoring system of the present invention.

FIG. 11 is a schematic view of a partial structure of the heating device and the detection frame of the present invention.

Fig. 12 is a schematic view of the structure of the heating apparatus of the present invention.

FIG. 13 is a schematic diagram of the sampling system of the present invention.

Fig. 14 is a schematic flow diagram of the water circulation heating system of the present invention.

FIG. 15 is a schematic flow diagram of a vehicle circulation system of the present invention.

FIG. 16 is a schematic flow diagram of a sampling system of the present invention.

List of reference numerals:

a constant temperature water area system 1;

the device comprises a constant-temperature water tank frame 1-1, a water tank bottom rod 1-1-1, a water tank bottom plate 1-1-2, a water tank side plate 1-1-3, a water tank frame bottom foot 1-1-4, a water tank back frame 1-1-5, 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;

a flow-through cell system 2;

2-1 parts of a circulating pool frame, 2-1-1 parts of side fixing blocks, 2-1-2 parts of a liquid collecting tank, 2-1-2-1 parts of side holes of the liquid collecting tank, 2-1-2-2 parts of bottom holes of the liquid collecting tank, 2-1-3 parts of a liquid discharge pipe, 2-1-4 parts of a cushion block, 2-1-4-1 parts of rubber feet, 2-1-5 parts of a top plate of the liquid collecting tank, 2-1-6 parts of a water area base, 2-1-6-1 parts of a solvent inlet, 2-1-6-2 parts of a solvent inlet joint, 2-1-6-3 parts of a water area water inlet joint, 2-1-6-4 parts of a water area water inlet joint, 2-1-6-5 parts of a base layer table, 2-1-7 parts of water area upper cover, 2-1-7-1 parts of upper cover fixing hole, 2-1-7-2 parts of water area water outlet, 2-1-7-3 parts of water area water outlet joint, 2-1-7-4 parts of knob fixing cylinder, 2-1-7-5 parts of upper cover layer table, 2-1-7-6 parts of upper cover sealing ring, 2-1-8 parts of knob, 2-1-8-1 parts of knob fixing piece, 2-1-9 parts of supporting rod, 2-1-10 parts of side fixing plate, 2-1-11 parts of shade connecting block, 2-1-12 parts of shade fixing rod, 2-1-13 parts of flow cell shade, 2-1-14 parts of flow cell back plate, 2-2 parts of flow cell, 2-3 parts of glass tube, 2-3 parts of, The device comprises a clamping structure 2-4, a hoisting plate 2-4-1, a hoisting rod 2-4-2, a hoisting rod top groove 2-4-2-1 and a clamping ring 2-4-3;

a lifting mechanism 3;

a circulation heating system 4;

the device comprises a heating device 4-1, a heating fixing plate 4-1-1, a heating wire 4-1-2, a connector 4-1-3, a straight connector 4-1-4, a connecting wire 4-1-5, a solvent inlet pipe 4-1-6, a solvent outlet pipe 4-1-7, a heating shade 4-1-8, a water circulating pump 4-2, a water tank outlet pipe 4-3, a water circulating main pipe 4-4, a shunt tee 4-5, a shunt pipe 4-6, a reflux branch pipe 4-7, a water supplementing tee 4-8, a water supplementing pipe 4-9, a water supplementing stop valve 4-10, a side branch tee 4-11 and a bypass pipe 4-12;

a solvent monitoring system 5;

the device comprises a detection rack 5-1, a rack bottom plate 5-1-1, a rack bottom plate through hole 5-1-1-1, a rack side plate 5-1-2, a rack back plate 5-1-3, a rack cover plate 5-1-4, a rack handle 5-1-5, a three-way valve island 5-2, a tube-moistening valve island 5-3, a pressure valve 5-4, a pressure valve fixing block 5-4-1, a photoelectric switch 5-5, a flow guide tube 5-6, a temperature sensor 5-7, a first support 5-8, a second support 5-9, a third support 5-10, a tube clamp 5-11, a tube clamp slot 5-11-1 and a fourth support 5-12;

a solvent circulating system 6;

a solvent circulating pump 6-1, a pulse valve 6-2, 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;

a sampling system 7;

a sampling mechanism 7-1, a sampling pipeline 7-2, a sampling valve 7-3 and a sampling pump 7-4.

Detailed Description

In order to make the technical scheme of the invention clearer and clearer, the invention is further described with reference to the accompanying drawings, and any scheme obtained by carrying out equivalent replacement and conventional reasoning on the technical characteristics of the technical scheme of the invention falls into the protection scope of the invention. The fixed connection, the fixed arrangement and the fixed structure mentioned in the embodiment are known technologies known to those skilled in the art, such as gluing, welding, screwing, bolt-nut connection, riveting and the like.

With the attached drawing, the closed-loop sampling system for drug dissolution by the flow cell method comprises a flow constant-temperature water system 1, a flow cell system, a lifting mechanism 3, a circulating heating system 4, a solvent monitoring system 5, a solvent circulating system 6 and a sampling system 7;

the constant temperature water area system 1 is used for preserving the heat of the menstruum in the menstruum cup 1-4; the constant-temperature water area system 1 comprises a constant-temperature water tank rack 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, wherein the constant-temperature water tank 1-2 is placed in the constant-temperature water tank rack 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 embedded in the solvent cup holder 1-3 to realize limiting and fixing; the solvent cup covers 1-5 are buckled on the top surface of each solvent cup 1-4;

the flow cell system 2 is used for the solvent to carry out the scouring and dissolving process on the medicine; the flow cell system 2 is arranged at the top end of the constant-temperature water area system 1, the flow cell system 2 comprises a flow cell rack 2-1, a flow cell 2-2 and a glass tube 2-3, the flow cell rack 2-1 is arranged on one side of the top surface of the solvent cup rack 1-3, and the flow cells 2-2 are fixed on the flow cell rack 2-1 and arranged in a transverse array; the glass tubes 2-3 are 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 carrying out integral lifting arrangement on 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 with 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 fixed with the side wall of the flow cell frame 2-1;

the circulation heating system 4 is used for carrying out water circulation heat exchange on the menstruum in the menstruum cup 1-4 and the menstruum in the flow cell 2-2 to realize temperature control; the circulation heating system 4 comprises a heating device 4-1 and a water circulation pump 4-2, wherein the heating device 4-1 is arranged on one side of the top surface of the solvent cup holder 1-3 and is arranged on one side of the circulation tank rack 2-1; the constant-temperature water tank 1-2 circulates water between the circulating pool system 2 and the constant-temperature water tank 1-2 through a water circulating pump 4-2 through a pipeline;

the solvent monitoring system 5 is used for monitoring the temperature and pressure of the circulating solvent and switching and controlling the circulation of the solvent; the solvent monitoring system 5 is arranged at the top end 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 circulating system 6 is used for circulating the solvent among the constant-temperature water system 1, the flow cell system 2 and the circulating heating system 4; the solvent circulating system 6 comprises a solvent circulating pump 6-1 and a pulse valve 6-2, the output end of the solvent circulating pump 6-1 is connected with the input end of the pulse valve 6-2 through a pipeline, and the output end of the pulse valve 6-2 is communicated through a pipeline and is sequentially connected to the circulating heating system 4, the circulating pool system 2 and the constant temperature water area system 1 and then connected to the input end of the solvent circulating pump 6-1;

the sampling system 7 is used for sampling the menstruum in the menstruum cups 1-4 in a time-sharing and quantitative manner; the sampling system 7 comprises a sampling mechanism 7-1, a sampling pipeline 7-2, a sampling valve 7-3 and a sampling pump 7-4, wherein the sampling mechanism 7-1 is connected into 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 communicated with the sampling pipeline 7-2.

Further, the constant-temperature water tank frame 1-1 comprises a water tank bottom rod 1-1-1, a water tank bottom plate 1-1-2, a water tank side plate 1-1-3, a water tank frame bottom foot 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 two sides, the water tank bottom plate 1-1-2 on one side is in an upward turning shape, and the water tank bottom plate 1-1-2 on one side is in a downward turning shape; the water tank side plates 1-1-3 are arranged on two sides of the water tank bottom plate 1-1-2 and fixedly assembled with the water tank bottom plate 1-1-2 through fasteners, and the top ends of the water tank side plates 1-1-3 on two sides are fixedly assembled with the solvent cup holder 1-3 through fasteners; the bottom foot 1-1-4 of the water tank frame is arranged at the bottom end of the bottom rod 1-1-1 of the water tank; the water tank back frame 1-1-5 is arranged on one side of the water tank side plate 1-1-3.

Further, the constant temperature water tank 1-2 is placed on the water tank bottom plate 1-1-2, the side edge of the top surface of the constant temperature water tank 1-2 is assembled with the solvent cup holder 1-3 through a fastener, and the side wall surface of the constant temperature water tank 1-2 is limited through a water tank side plate 1-1-3.

Further, the flow cell frame 2-1 comprises a side fixing block 2-1-1, a liquid collecting tank 2-1-2, a liquid discharge pipe 2-1-3, a cushion block 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, a side fixing plate 2-1-10, a shade connecting block 2-1-11, a shade fixing rod 2-1-12, a flow cell shade 2-1-13 and a flow cell back plate 2-1-14; the side fixing blocks 2-1-1 are arranged at two 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 the two 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; a liquid collecting groove side hole 2-1-2-1 is formed in the side wall of the liquid collecting groove 2-1-2, a liquid collecting groove bottom hole 2-1-2-2 is formed in the bottom end of the liquid collecting groove 2-1-2, one end of the liquid discharge pipe 2-1-3 is assembled and communicated with the liquid collecting groove bottom hole 2-1-2-2, and the bottom end of the liquid discharge 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 a fastener; 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 transverse array, a solvent inlet 2-1-6-1 is arranged in 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 connector 2-1-6-2, one side of the water area base 2-1-6 is provided with a water area water inlet 2-1-6-3, and the water area water inlet 2-1-6-3 is connected with a water area water inlet connector 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, an upper cover fixing hole 2-1-7-1 is arranged in 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 connector 2-1-7-3; two sides of the top surface of the water area upper cover 2-1-7 are provided with knob fixing cylinders 2-1-7-4, and the knobs 2-1-8 are connected with the knob fixing cylinders 2-1-7-4 in an inserting manner; the supporting rods 2-1-9 are arranged on two sides of the outer wall of the water area base 2-1-6, the bottom ends of the supporting rods 2-1-9 are vertically fixed with the liquid tank top plate 2-1-5, and the top ends of the supporting rods 2-1-9 are 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 two sides of the liquid tank top plate 2-1-5 symmetrically, and the bottom end of each side fixing plate 2-1-10 is fixed with the liquid tank top plate 2-1-5 through a fastener; the shade connecting blocks 2-1-11 are arranged on the top sides of the side fixing plates 2-1-10 on each side, and are assembled with the side fixing plates 2-1-10 through fasteners; two ends of the shade fixing rod 2-1-12 are rotatably arranged with the shade connecting blocks 2-1-11 at two sides through a rotating shaft; 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 a fastener; the flow cell back plate 2-1-14 is arranged on one side of the flow cell 2-2, and two sides of the flow cell back plate 2-1-14 are assembled with the side fixing plates 2-1-10 on two sides through fasteners.

Further, the length of the cushion block 2-1-4 is longer than the width of the liquid collecting groove 2-1-2, and two ends of the cushion block 2-1-4 extend out of two sides of the bottom surface of the liquid collecting groove 2-1-2; rubber feet 2-1-4-1 are arranged on the bottom surface of each cushion block 2-1-4 on each side, and the rubber feet 2-1-4-1 are fixed with the two 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 a rubber foot 2-1-4-1.

Furthermore, the clamping structure 2-4 comprises 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 two sides of the liquid collecting tank 2-1-2, the hoisting plate 2-4-1 on each side 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 two ends of the hoisting plate 2-4-1 are fixed with the cushion block 2-1-4 through fasteners; the lifting rod 2-4-2 is arranged at the top end of the solvent cup 1-4 rod, the lifting rod 2-4-2 and the solvent cup cover 1-5 are vertically fixed through threads, the circumferential direction of the top end of the lifting rod 2-4-2 is groove-shaped to form a lifting rod top groove 2-4-2-1, the lifting rod 2-4-2 penetrates through the lifting plate 2-4-1, and the clamping ring 2-4-3 is embedded into the lifting rod top groove 2-4-2-1, so that the solvent cup cover 1-5 and the lifting plate 2-4-1 are in lifting arrangement.

Furthermore, the number of the bottom holes 2-1-2-2 of the liquid collecting tank 2-1-2 is two, and each liquid discharge pipe 2-1-3 and each bottom hole 2-1-2-2 of the liquid collecting tank are arranged in a contraposition mode; the end part of the liquid discharge pipe 2-1-3 is in a flange shape, one end of the liquid discharge pipe 2-1-3 extends into the bottom hole 2-1-2-2 of the liquid collecting tank, the flange of the liquid discharge pipe 2-1-3 is attached to the inner bottom surface of the liquid collecting tank 2-1-2, and the liquid discharge pipe 2-1-3 is matched with the liquid collecting tank 2-1-2 through a fastening piece, so that the liquid discharge pipe 2-1-3 is vertically communicated with the liquid collecting tank 2-1-2.

Further, the top surface of the water area base 2-1-6 is of a layered structure to form a base layered platform 2-1-6-5, a base sealing ring 2-1-6-6 is embedded in the circumferential direction of the side wall of the base layered platform 2-1-6-5, the bottom end of the glass tube 2-3 is sleeved on the outer wall of the base layered platform 2-1-6-5 to realize insertion and 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 inlet 2-1-6-3 of the water area is communicated with the top surface of the base layer 2-1-6-5.

Furthermore, the solvent inlet connector 2-1-6-2 is arranged in the center of the top surface of the water area base 2-1-6, and the solvent inlet connector 2-1-6-2 is perpendicular to the water area base 2-1-6.

Further, the water area upper cover 2-1-7 is of a square structure; the center of the bottom surface of the water area upper cover 2-1-7 is of a layered platform-shaped structure to form an upper cover layer 2-1-7-5, an upper cover sealing ring 2-1-7-6 is embedded in the circumferential direction of the side wall of the upper cover layer 2-1-7-5, the top end of the glass tube 2-3 is sleeved on the outer wall of the upper cover layer 2-1-7-5 to realize insertion and 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 outlet 2-1-7-2 of the water area is communicated with the bottom surface of the upper cover layer 2-1-7-5.

Furthermore, the solvent inlet connector 2-1-6-2, the water inlet connector 2-1-6-4 and the water outlet connector 2-1-7-3 are luer connectors.

Further, the bottom end of the knob 2-1-8 extends into the knob fixing cylinder 2-1-7-4 correspondingly, and the knob 2-1-8 and the knob fixing cylinder 2-1-7-4 are fixed in a threaded manner; the side wall of each knob 2-1-8 is provided with a knob fixing piece 2-1-8-1, and the knob fixing pieces 2-1-8-1 are perpendicular to the knobs 2-1-8.

Furthermore, the circulating heating system 4 also comprises a water tank water outlet pipe 4-3, a water circulating main pipe 4-4, a shunt tee 4-5, a shunt pipe 4-6, a backflow branch pipe 4-7, a water supplementing tee 4-8, a water supplementing pipe 4-9, a water supplementing stop valve 4-10, a bypass tee 4-11 and a bypass pipe 4-12; one end of the water tank water outlet pipe 4-3 is communicated with the bottom end of the constant temperature water tank 1-2, and one end of the water tank water outlet pipe 4-3 is communicated with the suction end of the water circulating pump 4-2; one end of the water circulation main pipe 4-4 is communicated with the output end of the water circulation pump 4-2, and one end of the water circulation main pipe 4-4 is communicated with the shunt tee 4-5; one end of each shunt tube 4-6 is communicated with one end of each shunt tee 4-5, and each shunt tube 4-6 is inserted into each water area water inlet joint 2-1-6-4 through a manifold; two ends of each backflow branch pipe 4-7 are connected with one collecting tank side hole 2-1-2-1 and one water area water outlet connector 2-1-7-3; the water replenishing tee joint 4-8 is arranged on the water outlet pipe 4-3 of the water tank, the water replenishing pipe 4-9 is connected to one end of the water replenishing tee joint 4-8, and the water replenishing stop valve 4-10 is arranged on the water replenishing pipe 4-9; the bypass tee joint 4-11 is arranged on the water circulation main pipe 4-4, one end of the bypass pipe 4-12 is communicated with the bypass tee joint 4-11, and one end of the bypass pipe 4-12 is communicated with one side of the constant temperature water tank 1-2.

Further, the heating device 4-1 comprises a heating fixing plate 4-1-1, a heating wire 4-1-2, a connector 4-1-3, a straight connector 4-1-4, a connecting wire 4-1-5, a solvent inlet pipe 4-1-6, a solvent outlet pipe 4-1-7 and a heating shade 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 the heating fixing plate 4-1-1 and is fixedly connected with the connector 4-1-3 in an inserting manner; the connecting wire 4-1-5 is arranged on the top surface of the heating fixing plate 4-1-1, and two ends of the connecting wire 4-1-5 are fixedly inserted through the connectors 4-1-3; the plug-in connector of the connecting wire 4-1-5 and the plug-in connector of the heating wire 4-1-2 are respectively fixed with the two ends of the straight connector 4-1-4 by screw threads, so that the connecting wire 4-1-5 is connected with the heating wire 4-1-2; the solvent inlet pipes 4-1-6 are arranged in the heating water tank, and one end of each solvent inlet pipe 4-1-6 penetrates through the heating fixing plate 4-1-1 and is fixedly connected with the connectors 4-1-3 in an inserted manner; the solvent outlet pipes 4-1-7 are arranged in the heating water tank, one end of each solvent outlet pipe 4-1-7 penetrates through the heating fixing plate 4-1-1 and is fixedly connected with the connectors 4-1-3 in an inserting manner, and the bottom ends of the solvent inlet pipes 4-1-6 are communicated with the bottom ends of the solvent outlet pipes 4-1-7; the heating shade 4-1-8 is buckled on the top surface of the heating fixing plate 4-1-1, and one end of the heating shade 4-1-8 is rotated with the constant-temperature water tank rack 1-1 through a movable hinge.

Further, the heating wires 4-1-2 are arranged in two rows, each row of the heating wires 4-1-2 is arranged in two layers, and each layer of the heating wires 4-1-2 is in a circular coil-shaped structure; two adjacent heating wires 4-1-2 connected with the single connecting wire 4-1-5 are arranged in an upper-lower layer oblique mode.

Furthermore, the connecting wires 4-1-5 are in an inverted U-shaped structure.

Further, the solvent inlet pipe 4-1-6 is arranged in 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.

Further, the solvent monitoring system 5 comprises a detection rack 5-1, a three-way valve island 5-2, a tube wetting valve island 5-3, a pressure valve 5-4, a photoelectric switch 5-5, a flow guide tube 5-6 and a temperature sensor 5-7; the detection rack 5-1 is arranged on the top surface of the heating shade 4-1-8, and the detection rack 5-1 and the heating shade 4-1-8 are fixedly arranged; 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 through a first support 5-8; the tube moistening valve island 5-3 is arranged at one end inside the detection rack 5-1, and the tube moistening valve island 5-3 is supported and fixed through a second support 5-9; the pressure valve 5-4 is arranged at the middle end in the detection rack 5-1 and is arranged on one side of the three-way valve island 5-2, a pressure valve fixing block 5-4-1 is arranged on the outer side of the pressure valve 5-4, the pressure valve 5-4 is embedded into the pressure valve fixing block 5-4-1, and the pressure valve fixing block 5-4-1 is fixedly supported through a third support 5-10; the photoelectric switch 5-5 is arranged at one end of the interior of the detection rack 5-1 and is arranged at one side of the pressure valve 5-4, and the photoelectric switch 5-5 is fixed in the detection rack 5-1 through a pipe clamp 5-11; the draft tube 5-6 is arranged at the top end of the interior of the detection rack 5-1 and is arranged on one side of the tube moistening valve island 5-3, and the draft tube 5-6 is fixedly supported by a fourth support 5-12; the temperature sensor 5-7 is vertically fixed at the bottom end of the draft tube 5-6, and the end part of the temperature sensor 5-7 extends into the draft tube 5-6; the solvent outlet pipe 4-1-7 extends into the detection rack 5-1 through a pipeline and is communicated with the inlet end corresponding to the three-way valve island 5-2; the outlet at the side end of the three-way valve island 5-2 is communicated with one end corresponding to the 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 into the pipe clamp 5-11; the top outlet of the three-way valve island 5-2 is communicated with the bottom end of the corresponding moistening pipe valve island 5-3 through a pipeline; an outlet at one end of the wetting tube valve island 5-3 is communicated with an input port of the solvent cup cover 1-5 through a pipeline; an outlet at one end of the tube moistening valve island 5-3 is communicated with the corresponding flow guide tube 5-6 through a pipeline.

Further, the detection rack 5-1 comprises 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 rack handles 5-1-5, the rack side plates 5-1-2 are symmetrically arranged on two sides, the top edge and the bottom edge of each rack side plate 5-1-2 are bent, the bottom sides of the rack side plates 5-1-2 on the two sides are fixed with the top surface of the heating shade 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 the two sides and fixed with the rack side plates 5-1-2 on the two sides, and one side of the surface of the rack bottom plate 5-1-1 is provided with a rack bottom plate through hole 5-1-1; the section of the rack back plate 5-1-3 is of a T-shaped structure, the rack back plate 5-1-3 is arranged at one end of the rack side plates at two sides, and the rack back plate 5-1-3 is fixed with the rack side plates 5-1-2 at two sides; the rack cover plate 5-1-4 is buckled on the top side of the rack side plate 5-1-2, and two sides of the rack cover plate 5-1-4 are fixed with the top sides of the rack side plates 5-1-2 at two sides; the rack handle 5-1-5 is arranged on one side of the rack side plate 5-1-2 on one side and is vertically fixed with the rack side plate 5-1-2.

Furthermore, the three-way valve island 5-2 is arranged at the top end of the through hole 5-1-1-1 of the bottom plate of the rack in an aligned mode; the first support 5-8 is arranged on one side of the three-way valve island 5-2, the section of the first support 5-8 is of an L-shaped structure, the bottom surface of the first support 5-8 is fixed with the rack bottom plate 5-1-1, and the top side surface of the second support 5-9 is fixed with the side surface of the three-way valve island 5-2.

Further, the tube moistening valve island 5-3 is arranged at the top end of the three-way valve island 5-2 in an aligned mode; the second supports 5-9 are arranged at two ends of the tube moistening valve island 5-3, the section of each second support 5-9 is of an L-shaped structure, the bottom surface of each second support 5-9 is fixed with the rack bottom plate 5-1-1, the top side surface of each second support 5-9 is fixed with the end surface of the tube moistening valve island 5-3, and the tube moistening valve island 5-3 and the three-way valve island 5-2 are arranged in the same direction.

Further, the pressure valves 5-4 are arranged in a transverse array, and each pressure valve 5-4 is arranged in a contraposition with the outlet of the three-way valve island 5-2; the third support 5-10 is arranged on the bottom side of the pressure valve 5-4, the third support 5-10 is of a Z-shaped structure, the bottom surface of the third support 5-10 is fixed with the rack bottom plate 5-1-1, and the top surface of the third support 5-10 is fixed with the pressure valve fixing block 5-4-1.

Further, the pipe clamps 5-11 are transversely arranged on the top surface of the rack bottom plate 5-1-1 in an array mode, the top surface of each pipe clamp 5-11 is in a groove shape to form a pipe clamp clamping groove 5-11-1, and each pipe clamp clamping groove 5-11-1 is arranged in an alignment mode with the pressure valve 5-4; the photoelectric switch 5-5 is arranged on the top surface of the pipe clamp 5-11 and spans the top surface of the pipe clamp clamping groove 5-11-1.

Furthermore, the flow guide pipes 5-6 are arranged in a transverse array, the flow guide pipes 5-6 and the tube moistening valve island 5-3 are arranged at the same height, and each flow guide pipe 5-6 and the outlet of the tube moistening valve island 5-3 are arranged in an alignment manner; the fourth support 5-12 is arranged between the third support 5-10 and the pipe clamp 5-11, the section of the fourth support 5-12 is of a T-shaped structure, the bottom surface of the fourth support 5-12 is fixed with the rack bottom plate 5-1-1, and the flow guide pipe 5-6 is arranged on the top surface of the fourth support 5-12.

Further, the solvent circulating system 6 further comprises a first solvent tube 6-3, a second solvent tube 6-4, a third solvent tube 6-5, a fourth solvent tube 6-6 and a fifth solvent tube 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 circulating pump 6-1; one end of the third solvent pipe 6-5 is communicated with the output end of the solvent circulating pump 6-1, and one end of the third solvent pipe 6-5 is connected with 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 with the solvent inlet pipe 4-1-6; one end of the fifth solvent pipe 6-7 is connected with one end of the draft tube 5-6, and one end of the fifth solvent pipe 6-7 is connected with the solvent inlet 2-1-6-1 of the flow cell 2-2.

Further, the solvent circulating pump 6-1 adopts a piston injection pump; the number of the solvent circulating pumps 6-1 is two, one end of the second solvent pipe 6-4 is connected with the suction end of each solvent circulating pump 6-1 through a manifold, and one end of the third solvent pipe 6-5 is connected with the output end of each solvent circulating pump 6-1 through a manifold.

Furthermore, the heating wire 4-1-2, the water circulating pump 4-2, the solvent circulating 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 tube moistening valve island 5-3, the photoelectric switch 5-5 and the temperature sensor 5-7 are electrically connected with an external controller through leads; the controller controls the set temperature value of the heating wire 4-1-2, the controller controls the opening and closing of the water circulating pump 4-2, the solvent circulating 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 tube moistening valve island 5-3, the photoelectric switch 5-5 uploads a signal to the controller, and the temperature sensor 5-7 uploads temperature information to the controller.

1. supporting and fixing the medicine supporting structure in the flow cell 2-2, inserting the flow cell 2-2 into the upper cover fixing hole 2-1-7-1, inserting and fixing the bottom end of the flow cell 2-2 and the solvent inlet joint 2-1-6-2, and rotating the knob 2-1-8 to enable the knob fixing piece 2-1-8-1 to be buckled at the end part of the flow cell 2-2; one end of the flow cell 2-2 is communicated with one end of a first solvent pipe 6-3, so that the flow cell 2-2 is connected into a solvent circulating system 6;

2. starting the adjusting lifting mechanism 3, lowering the lifting mechanism 3 to the lowest point, driving the flow cell system 2 to descend to the lowest point position by the lifting mechanism 3, and pressing and attaching the solvent cup covers 1-5 to the solvent cup holes 1-4;

3. starting heating work of the heating wire 4-1-2, and heating water in the constant-temperature water tank 1-2 by the heating wire 4-1-2;

4. starting a water circulating pump 4-2, sucking water in a constant-temperature water tank 1-2 into a suction end of a water circulating pump 4-2 through a water tank water outlet pipe 4-3, enabling the water to flow into a shunt pipe 4-6 through a shunt tee 4-5 under the pumping action of the water circulating pump 4-2, inputting the water into a glass pipe 2-3 through a manifold through a water inlet 2-1-6-3 of a water area respectively, injecting the water into a liquid collecting tank 2-1-2 from a backflow branch pipe 4-7 after the glass pipe 2-3 is filled, and re-injecting the water in the liquid collecting tank 2-1-2 into the constant-temperature water tank 1-2 through a liquid discharge pipe 2-1-3;

5. an outlet end of the wetting tube valve island 5-3 is directly communicated with an input port of the solvent cup cover 1-5 through a conduit; starting a solvent circulating pump 6-1, sucking a solvent in a solvent cup 1-4 into the suction end of the solvent circulating pump 6-1 through a second solvent pipe 6-4, conveying the solvent to a pulse valve 6-2 through a third solvent pipe 6-5 under the pumping action of the solvent circulating pump 6-1, carrying out pulse conveying action on the solvent by the pulse valve 6-2 to simulate the blood circulation of a human body, allowing the solvent to enter a constant-temperature water tank 1-2 through a fourth solvent pipe 6-6 for heat exchange, allowing the solvent to flow through a heating device 4-1 and a solvent monitoring system 5, and directly refluxing the solvent to the solvent cup 1-4; meanwhile, the solvent is filled in the flow guide pipe 5-6, and the temperature of the solvent is monitored;

6. when the temperature sensor 5-7 monitors that the temperature of the solvent reaches 37 ℃, the output end of the draft tube 5-6 is communicated with the solvent inlet 2-1-6-1 of the flow cell 2-2 through a fifth solvent tube 6-7; the solvent flowing into the solvent monitoring system 5 flows into the bottom end of the flow cell 2-2 through the wetting tube valve island 5-3 and the fifth solvent tube 6-7, and is flushed with the drug and then re-injected into the solvent cup 1-4 through the first solvent tube 6-3;

7. starting the sampling pump 7-4 and opening the sampling valve 7-3, sucking the solvent in the solvent cup 1-4 into the suction end of the sampling pump 7-4 through the sampling pipeline 7-2, and sending the solvent into the sampling mechanism 7-1 through the pumping action of the sampling pump 7-4, and carrying out time-sharing quantitative sampling by the sampling mechanism 7-1.

The invention has the beneficial effects that:

Claims

1. A closed-loop sampling system for drug dissolution by a flow cell method is characterized by comprising a flow constant-temperature water area system (1), a flow cell system (2), a lifting mechanism (3), a circulating heating system (4), a solvent monitoring system (5), a solvent circulating system (6) and a sampling system (7);

the constant temperature water area system (1) is used for preserving the heat of the menstruum in the menstruum cup (1-4); the constant-temperature water area system (1) comprises a constant-temperature water tank rack (1-1), a constant-temperature water tank (1-2), a solvent cup rack (1-3), a solvent cup (1-4) and a solvent cup cover (1-5), wherein the constant-temperature water tank (1-2) is placed in the constant-temperature water tank rack (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 embedded in the solvent cup holder (1-3) to realize limiting and fixing; the solvent cup covers (1-5) are buckled on the top surfaces of the solvent cups (1-4);

the flow cell system (2) is used for the solvent to carry out the scouring and dissolving process on the medicine; the circulating pond system (2) is arranged at the top end of the constant-temperature water area system (1), the circulating pond system (2) comprises a circulating pond rack (2-1), a circulating pond (2-2) and a glass tube (2-3), the circulating pond rack (2-1) is arranged on one side of the top surface of the solvent cup rack (1-3), and the circulating pond (2-2) is fixed on the circulating pond rack (2-1) and arranged in a transverse array; the glass tubes (2-3) are correspondingly sleeved on the outer wall of each flow cell (2-2); the solvent cup cover (1-5) is hoisted with the circulating pool rack (2-1) through a clamping structure (2-4);

the lifting mechanism (3) is used for carrying out integral lifting arrangement on the flow cell system (2); the lifting mechanism (3) is arranged on one side of the constant-temperature water tank rack (1-1), the bottom end of the lifting mechanism (3) is fixed with the top surface of the constant-temperature water tank rack (1-1), and one side of the top end of the lifting mechanism (3) is fixed with the side wall of the circulating pool rack (2-1);

the circulation heating system (4) is used for carrying out water circulation heat exchange on the menstruum in the menstruum cup (1-4) and the menstruum in the flow cell (2-2) to realize temperature control; the circulation heating system (4) comprises a heating device (4-1) and a water circulation pump (4-2), wherein the heating device (4-1) is arranged on one side of the top surface of the solvent cup holder (1-3) and is arranged on one side of the circulating pool rack (2-1); the constant-temperature water tank (1-2) circulates water between the circulating pool system (2) and the constant-temperature water tank (1-2) through a water circulating pump (4-2) through a pipeline;

the menstruum monitoring system (5) is used for monitoring the temperature and the pressure of the circulating menstruum and switching and controlling the circulation of the menstruum; the solvent monitoring system (5) is arranged at the top end 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 circulating system (6) is used for circulating the solvent among the constant-temperature water area system (1), the circulating pool system (2) and the circulating heating system (4); the solvent circulating system (6) comprises a solvent circulating pump (6-1) and a pulse valve (6-2), the output end of the solvent circulating pump (6-1) is connected with the input end of the pulse valve (6-2) through a pipeline, and the output end of the pulse valve (6-2) is connected with the circulating heating system (4), the circulating pool system (2) and the constant-temperature water area system (1) in sequence through pipeline communication and then connected with the input end of the solvent circulating pump (6-1);

the sampling system (7) is used for sampling the menstruum in the menstruum cup (1-4) in a time-sharing and quantitative way; the sampling system (7) comprises a sampling mechanism (7-1), a sampling pipeline (7-2), a sampling valve (7-3) and a sampling pump (7-4), wherein the sampling mechanism (7-1) is connected into 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 communicated with the sampling pipeline (7-2).

2. The flow cell method drug dissolution closed loop sampling system according to claim 1, wherein the thermostatic water tank frame (1-1) comprises a water tank bottom rod (1-1-1), a water tank bottom plate (1-1-2), a water tank side plate (1-1-3), a water tank frame foot (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 two sides, the water tank bottom plate (1-1-2) on one side is in an upward folded shape, and the water tank bottom plate (1-1-2) on one side is in a downward folded shape; the water tank side plates (1-1-3) are arranged on two sides of the water tank bottom plate (1-1-2) and fixedly assembled with the water tank bottom plate (1-1-2) through fasteners, and the top ends of the water tank side plates (1-1-3) on two sides are fixedly assembled with the solvent cup holder (1-3) through fasteners; the bottom foot (1-1-4) of the water tank frame is 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 plate (1-1-3).

3. The flow cell process drug dissolution closed loop sampling system of claim 1, the circulating pool frame (2-1) comprises side fixing blocks (2-1-1), a liquid collecting tank (2-1-2), a liquid discharge 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 supporting rod (2-1-9), side fixing plates (2-1-10), a cover connecting block (2-1-11), a cover fixing rod (2-1-12), a circulating pool cover (2-1-13) and a circulating pool back plate (2-1-14); the side fixing blocks (2-1-1) are arranged at two 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 the two 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; a liquid collecting groove side hole (2-1-2-1) is formed in the side wall of the liquid collecting groove (2-1-2), a liquid collecting groove bottom hole (2-1-2-2) is formed in the bottom end of the liquid collecting groove (2-1-2), one end of the liquid discharge pipe (2-1-3) is assembled and communicated with the liquid collecting groove bottom hole (2-1-2-2), and the bottom end of the liquid discharge 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 a fastener; 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 transverse array, a solvent inlet (2-1-6-1) is formed in 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 connector (2-1-6-2), one side of the water area base (2-1-6) is provided with a water area water inlet (2-1-6-3), and the water area water inlet (2-1-6-3) is connected with a water area water inlet connector (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), an upper cover fixing hole (2-1-7-1) is formed in the center of the water area upper cover (2-1-7), a water area water outlet (2-1-7-2) is formed in 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 connector (2-1-7-3); knob fixing cylinders (2-1-7-4) are arranged on two sides of the top surface of the water area upper cover (2-1-7), and the knobs (2-1-8) are connected with the knob fixing cylinders (2-1-7-4) in an inserting mode; the supporting rods (2-1-9) are arranged on two sides of the outer wall of the water area base (2-1-6), the bottom ends of the supporting rods (2-1-9) are vertically fixed with the liquid tank top plate (2-1-5), and the top ends of the supporting rods (2-1-9) are 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 two sides of the liquid tank top plate (2-1-5) symmetrically, and the bottom end of each side fixing plate (2-1-10) is fixed with the liquid tank top plate (2-1-5) through a fastening piece; the shade connecting block (2-1-11) is arranged at the top side of the side fixing plate (2-1-10) at each side, and is assembled with the side fixing plate (2-1-10) through a fastener; two ends of the shade fixing rod (2-1-12) are rotatably arranged with the shade connecting blocks (2-1-11) at two sides through a rotating shaft; the flow cell shade (2-1-13) is attached to the side wall of the shade connecting block (2-1-11), and the flow cell shade (2-1-13) is assembled with the shade fixing rod (2-1-12) through a fastener; the flow cell back plate (2-1-14) is arranged on one side of the flow cell (2-2), and two sides of the flow cell back plate (2-1-14) are assembled with the side fixing plates (2-1-10) on two sides through fasteners.

4. The closed-loop drug dissolution sampling system adopting the flow cell method as claimed in claim 1, wherein the clamping structure (2-4) comprises a hanging plate (2-4-1), a hanging rod (2-4-2) and a collar (2-4-3), the hanging plate (2-4-1) is arranged at two sides of the liquid collecting tank (2-1-2), the hanging plate (2-4-1) at each side 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 two ends of the hanging plate (2-4-1) are fixed with the cushion block (2-1-4) through fasteners; the device comprises a solvent cup (1-4) and a hoisting rod (2-4-2), wherein 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) and the solvent cup cover (1-5) are vertically fixed 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 a clamping ring (2-4-3) is embedded into the hoisting rod top groove (2-4-2-1) to realize that the solvent cup cover (1-5) and the hoisting plate (2-4-1) are in hoisting setting.

5. The closed-loop sampling system for drug dissolution by the flow cell method according to claim 1, wherein the circulation heating system (4) further comprises 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 supplement tee (4-8), a water supplement pipe (4-9), a water supplement stop valve (4-10), a bypass tee (4-11) and a bypass pipe (4-12); one end of the water tank water outlet pipe (4-3) is communicated with the bottom end of the constant temperature water tank (1-2), and one end of the water tank water outlet pipe (4-3) is communicated with the suction end of the water circulating pump (4-2); one end of the water circulation main pipe (4-4) is communicated with the output end of the water circulation pump (4-2), and one end of the water circulation main pipe (4-4) is communicated with the flow dividing tee joint (4-5); one end of each shunt tube (4-6) is communicated with one end of each shunt tee (4-5), and each shunt tube (4-6) is inserted into each water area water inlet joint (2-1-6-4) through a manifold; both ends of each return branch pipe (4-7) are connected with one collecting tank side hole (2-1-2-1) and one water area water outlet joint (2-1-7-3); the water replenishing tee joint (4-8) is arranged on the water outlet pipe (4-3) of the water tank, the water replenishing pipe (4-9) is connected to one end of the water replenishing tee joint (4-8), and the water replenishing stop valve (4-10) is arranged on the water replenishing pipe (4-9); the bypass tee joint (4-11) is arranged on the water circulation main pipe (4-4), one end of the bypass pipe (4-12) is communicated with the bypass tee joint (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. The closed loop sampling system for drug dissolution by the flow cell method according to claim 1, wherein the heating device (4-1) comprises a heating fixing plate (4-1-1), a heating wire (4-1-2), a connecting head (4-1-3), a straight head (4-1-4), a connecting wire (4-1-5), a solvent inlet pipe (4-1-6), a solvent outlet pipe (4-1-7) and a heating shade (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 the heating fixing plate (4-1-1) and is fixedly inserted into the connector (4-1-3); the connecting wire (4-1-5) is arranged on the top surface of the heating fixing plate (4-1-1), and two ends of the connecting wire (4-1-5) are fixedly inserted through the connectors (4-1-3); the plug-in connector of the connecting wire (4-1-5) and the plug-in connector of the heating wire (4-1-2) are respectively in threaded fixation with two ends of the straight connector (4-1-4), so that the connecting wire (4-1-5) is connected with the heating wire (4-1-2); the solvent inlet pipes (4-1-6) are arranged in the heating water tank, and one end of each solvent inlet pipe (4-1-6) penetrates through the heating fixing plate (4-1-1) and extends out of the heating fixing plate, and is fixedly connected with the connectors (4-1-3) in an inserted manner; the solvent outlet pipes (4-1-7) are arranged in the heating water tank, one end of each solvent outlet pipe (4-1-7) penetrates through the heating fixing plate (4-1-1) and extends out of the heating fixing plate, and is fixedly connected with the connectors (4-1-3) in an inserting mode, and the bottom ends of the solvent inlet pipes (4-1-6) are communicated with the bottom ends of the solvent outlet pipes (4-1-7); the heating shade (4-1-8) is buckled on the top surface of the heating fixing plate (4-1-1), and one end of the heating shade (4-1-8) is rotated with the constant-temperature water tank rack (1-1) through a movable hinge.

7. The closed-loop sampling system for drug dissolution by flow cell method according to claim 1, wherein the solvent monitoring system (5) comprises a detection frame (5-1), a three-way valve island (5-2), a tube-wetting valve island (5-3), a pressure valve (5-4), a photoelectric switch (5-5), a flow guide tube (5-6) and a temperature sensor (5-7); the detection rack (5-1) is arranged on the top surface of the heating shade (4-1-8), and the detection rack (5-1) and the heating shade (4-1-8) are fixedly arranged; the three-way valve island (5-2) is arranged at one end of the interior of the detection rack (5-1), and the three-way valve island (5-2) is supported and fixed through a first support (5-8); the tube moistening valve island (5-3) is arranged at one end of the interior of the detection rack (5-1), and the tube moistening valve island (5-3) is supported and fixed through a second support (5-9); the pressure valve (5-4) is arranged at the middle end in the detection rack (5-1) and is arranged on one side of the three-way valve island (5-2), a pressure valve fixing block (5-4-1) is arranged on the outer side of the pressure valve (5-4), the pressure valve (5-4) is embedded into the pressure valve fixing block (5-4-1), and the pressure valve fixing block (5-4-1) is fixedly supported through a third support (5-10); the photoelectric switch (5-5) is arranged at one end of the interior of the detection rack (5-1) and is arranged at one side of the pressure valve (5-4), and the photoelectric switch (5-5) is fixed in the detection rack (5-1) through a pipe clamp (5-11); the draft tube (5-6) is arranged at the top end of the interior of the detection rack (5-1) and is arranged on one side of the tube moistening valve island (5-3), and the draft tube (5-6) is fixedly supported through a fourth support (5-12); the temperature sensor (5-7) is vertically fixed at the bottom end of the draft tube (5-6), and the end part of the temperature sensor (5-7) extends into the draft tube (5-6); the solvent outlet pipe (4-1-7) extends into the detection rack (5-1) through a pipeline and is communicated with the inlet end corresponding to the three-way valve island (5-2); the side end outlet of the three-way valve island (5-2) is communicated with one end corresponding to the 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 into the pipe clamp (5-11); the top outlet of the three-way valve island (5-2) is communicated with the bottom end of the corresponding moistening pipe valve island (5-3) through a pipeline; an outlet at one end of the wetting tube valve island (5-3) is communicated with an input port of the solvent cup cover (1-5) through a pipeline; an outlet at one end of the tube moistening valve island (5-3) is communicated with the corresponding flow guide tube (5-6) through a pipeline.

8. The closed-loop sampling system for drug dissolution by the flow cell method according to claim 6, wherein the detection rack (5-1) comprises 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 two sides, the top edge and the bottom edge of each rack side plate (5-1-2) are bent, the bottom sides of the rack side plates (5-1-2) on two sides are fixed with the top surface of the heating shade (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 two sides, the side plates are fixed with the side plates (5-1-2) of the machine frame at two sides, and a through hole (5-1-1-1) of the bottom plate of the machine frame is arranged at one side of the surface of the bottom plate (5-1-1) of the machine frame; the section of the rack back plate (5-1-3) is of a T-shaped structure, the rack back plate (5-1-3) is arranged at one end of the rack side plates at two sides, and the rack back plate (5-1-3) is fixed with the rack side plates (5-1-2) at two sides; the rack cover plate (5-1-4) is buckled on the top side of the rack side plate (5-1-2), and two sides of the rack cover plate (5-1-4) are fixed with the top sides of the rack side plates (5-1-2) on two sides; the rack handle (5-1-5) is arranged on one side of the rack side plate (5-1-2) and is vertically fixed with the rack side plate (5-1-2).

9. The flow cell method drug-eluting closed-loop sampling system according to claim 1, wherein the solvent circulation system (6) further comprises a first solvent tube (6-3), a second solvent tube (6-4), a third solvent tube (6-5), a fourth solvent tube (6-6) and a fifth solvent tube (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 circulating pump (6-1); one end of the third solvent pipe (6-5) is communicated with the output end of the solvent circulating pump (6-1), and one end of the third solvent pipe (6-5) is connected with 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 draft tube (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).

10. The flow cell drug-eluting closed-loop sampling system according to any one of claims 1-9, wherein a method of using the flow cell drug-eluting closed-loop sampling system is provided, comprising the steps of:

(1) supporting and fixing the medicine supporting structure in the flow cell (2-2), inserting the flow cell (2-2) into the upper cover fixing hole (2-1-7-1), inserting and fixing the bottom end of the flow cell (2-2) and the solvent inlet joint (2-1-6-2), and rotating the knob (2-1-8) to enable the knob fixing piece (2-1-8-1) to be buckled at the end part of the flow cell (2-2); one end of the flow cell (2-2) is communicated with one end of the first solvent pipe (6-3) to realize that the flow cell (2-2) is connected into the solvent circulating system (6);

(2) starting the adjusting lifting mechanism (3), lowering the lifting mechanism (3) to the lowest point, driving the circulating pool system (2) to descend to the lowest point position by the lifting mechanism (3), and pressing and attaching the solvent cup cover (1-5) to the position of the solvent cup (1-4) hole;

(3) starting the heating operation of the heating wire (4-1-2), and heating the water in the constant-temperature water tank (1-2) by the heating wire (4-1-2);

(4) starting a water circulating pump (4-2), sucking water in a constant-temperature water tank (1-2) into a suction end of the water circulating pump (4-2) through a water tank water outlet pipe (4-3), enabling the water to flow into a shunt pipe (4-6) through a shunt tee (4-5) under the pumping action of the water circulating pump (4-2), inputting the water into a glass pipe (2-3) through a manifold through a water inlet (2-1-6-3), injecting the glass pipe (2-3) into a liquid collecting tank (2-1-2) from a backflow branch pipe (4-7) after the glass pipe (2-3) is filled, and re-injecting the water in the liquid collecting tank (2-1-2) into the constant-temperature water tank (1-2) through a liquid discharge pipe (2-1-3);

(5) directly communicating an outlet end of the wetting tube valve island (5-3) with an input port of the solvent cup cover (1-5) through a conduit; the solvent circulating pump (6-1) is started, the solvent in the solvent cup (1-4) is sucked into the suction end of the solvent circulating pump (6-1) through the second solvent pipe (6-4), the solvent is conveyed to the pulse valve (6-2) through the third solvent pipe (6-5) under the pumping action of the solvent circulating pump (6-1), the pulse valve (6-2) performs pulse conveying action on the solvent to simulate human blood circulation, the solvent enters the constant-temperature water tank (1-2) through the fourth solvent pipe (6-6) to perform heat exchange, the solvent flows through the heating device (4-1) and the solvent monitoring system (5), and the solvent directly flows back into the solvent cup (1-4); meanwhile, the solvent is filled in the flow guide pipe (5-6) to monitor the temperature of the solvent;

(6) when the temperature sensor (5-7) monitors that the temperature of the solvent reaches 37 ℃, the output end of the draft tube (5-6) is communicated with the solvent inlet (2-1-6-1) of the flow cell (2-2) through a fifth solvent tube (6-7); the menstruum flowing into the menstruum monitoring system (5) flows into the bottom end of the flow cell (2-2) through a fifth menstruum tube (6-7) through a tube wetting valve island (5-3), and is flushed with the medicament and then re-injected into the menstruum cup (1-4) through the first menstruum tube (6-3);

(7) starting the sampling pump (7-4) and opening the sampling valve (7-3), sucking the solvent in the solvent cup (1-4) into the suction end of the sampling pump (7-4) through the sampling pipeline (7-2), and sending the solvent into the sampling mechanism (7-1) through the pumping action of the sampling pump (7-4), wherein the sampling mechanism (7-1) performs time-sharing quantitative sampling.