Closed-loop sampling device for medicine dissolution by flow cell method

Abstract

The utility model relates to a closed-loop sampling device for medicine dissolution by a flow cell method. The closed-loop sampling device for medicine dissolution by the flow cell method comprises a metering solvent bottle used for preparing and containing a solvent to be detected and monitoring the volume of the solvent; the flow cell system is connected with the metering solvent bottle through a system conduit and comprises a flow cell and a sampler; the liquid supplementing assembly is connected with the metering solvent bottle through a liquid supplementing guide pipe and is used for timely and quantitatively supplementing the solvent; the solvent bottle comprises a solvent bottle body and a solvent bottle cap, the solvent bottle cap is in sealed connection with the solvent bottle body, and the solvent bottle cap comprises a system through hole and a liquid supplementing through hole; and a jacket is arranged outside the solvent bottle body and comprises a jacket inlet and a jacket outlet. According to the application, accurate and stable sampling can be realized, the accuracy of the drug detection concentration and the detection method can be improved, the volume of a solvent is dynamically monitored so as to timely supplement liquid and ensure that the volume of the solvent is not changed, and the temperature of the solvent is controlled through a jacket layer heat source so as to ensure that the solvent and a drug are subjected to a dissolution test at the optimal suitable temperature.

Description

Technical Field

[0001] The present application relates to the technical field of drug testing devices, and in particular to a closed-loop sampling device for drug dissolution using a circulation cell method. Background Art

[0002] In the process of drug development and formulation testing, drug dissolution testing is a crucial step. This test often uses the flow cell method, which simulates the in vivo circulation of the drug formulation in the human body by continuously flushing the drug formulation. The sampling methods in the flow cell method are divided into two types: open-loop sampling system and closed-loop sampling system. For drugs such as ocular implants, due to their low drug loading and long release cycle, more accurate dissolution testing is required, and a closed-loop sampling system is generally used for dissolution testing.

[0003] The characteristic of the closed-loop sampling system is that the same batch of solvent is used in a continuous cycle, which can ensure the continuity and stability of the experiment. However, in the existing technology, the closed-loop sampling system in the circulation cell method cannot be replenished, and long-term and multiple sampling will lead to insufficient solvent, which brings challenges to the dissolution test of ocular implants. Excessive increase in the volume of solvent will reduce the concentration of the drug in the solvent, making the test more difficult. Utility Model Content

[0004] Based on this, it is necessary to provide a closed-loop sampling device for drug dissolution using a circulation pool method to address the problem that fluid replacement cannot be performed and long-term and multiple sampling will lead to insufficient solvent.

[0005] A closed-loop sampling device for drug dissolution by a circulation cell method. The closed-loop sampling device for drug dissolution by a circulation cell method comprises:

[0006] Measuring solvent bottle, used to prepare and hold the solvent to be tested, and monitor the volume of the solvent;

[0007] A circulation cell system, connected to the metering solvent bottle through a system conduit, used for circulating the solvent to be tested in the metering solvent bottle during the circulation cell dissolution test and sampling during the circulation cell test, including a circulation cell and a sampler;

[0008] A fluid replenishment component, connected to the metering solvent bottle via a fluid replenishment conduit, and used for timely and quantitatively replenishing the solvent in the metering solvent bottle;

[0009] The metering solvent bottle comprises a solvent bottle body and a solvent bottle cap, wherein the solvent bottle cap is sealed and connected to the solvent bottle body, and the solvent bottle cap comprises a system through hole and a fluid infusion through hole; the system through hole is used to accommodate a system conduit connected to the circulation pool system; the fluid infusion through hole is used to accommodate a fluid infusion conduit connected to the fluid infusion assembly;

[0010] A jacket is arranged outside the solvent bottle body, and the jacket is used to pass a heat source and utilize the heat source to perform timed heating and temperature control on the solvent.

[0011] In one embodiment, the system through hole includes an inlet through hole, an outlet through hole and a sampling through hole, and the system conduit includes an inlet conduit, an outlet conduit and a sampling conduit;

[0012] One end of the inlet conduit is connected to the flow outlet of the circulation pool, and the other end of the inlet conduit passes through the inlet through-hole. One end of the outlet conduit is connected to the flow inlet of the circulation pool, and the other end of the outlet conduit passes through the outlet through-hole. One end of the sampling conduit is connected to the sampler, and the other end of the sampling conduit passes through the sampling through-hole.

[0013] In one embodiment, the portion of the outlet conduit located inside the measuring solvent bottle and the portion of the sampling conduit located inside the measuring solvent bottle are both long conduits, and the tube mouths of the long conduits are close to the inner bottom of the measuring solvent bottle, and the portion of the inlet conduit located inside the measuring solvent bottle and the portion of the infusion conduit located inside the measuring solvent bottle are both short conduits, and the tube mouths of the short conduits are located below the liquid level of the solvent in the measuring solvent bottle and close to the liquid surface.

[0014] In one embodiment, the outlet conduit and the inlet conduit are symmetrically arranged about the center of the solvent bottle cap, the infusion conduit and the sampling conduit are symmetrically arranged about the center of the solvent bottle cap, and the long conduit and the short conduit are equidistantly arranged.

[0015] In one embodiment, the solvent bottle cap further includes an exhaust hole, and the exhaust hole is used to balance the internal pressure and external pressure of the metering solvent bottle.

[0016] In one of the embodiments, the exhaust through hole is covered with an exhaust baffle, and the exhaust baffle is provided with a plurality of evenly distributed small holes, and the exhaust baffle is used to reduce the dust from entering the metering solvent bottle during long-term testing.

[0017] In one embodiment, the fluid infusion assembly includes a fluid infusion cup, the fluid infusion cup is connected to the fluid infusion catheter, and the fluid infusion catheter is provided with a fluid infusion pump.

[0018] In one embodiment, the fluid infusion component further includes a precision liquid level sensor, which is disposed at the fluid infusion catheter port located inside the metering solvent bottle, and a fluid infusion controller is connected between the precision liquid level sensor and the fluid infusion pump.

[0019] In one embodiment, the metering solvent bottle further includes a stirring device, and the stirring device is used to apply stirring force to the solvent in the metering solvent bottle and maintain uniform distribution of the drug in the solvent.

[0020] In one embodiment, the outer wall of the solvent bottle of the measuring solvent bottle is marked with scales indicating the corresponding solvent volume.

[0021] The above-mentioned closed-loop sampling device for drug dissolution by the circulation cell method connects the metering solvent bottle to the closed-loop sampling system and the rehydration component through the system catheter respectively. After starting the dissolution experiment, the solvent to be detected in the metering solvent bottle is driven to circulate between the circulation cell and the metering solvent bottle through the circulation cell. During the flow process, the solvent to be detected is contacted with the experimental sample, and the solvent after contacting the experimental sample is stirred in the metering solvent bottle. Then, quantitative sampling is taken from the metering solvent bottle according to the sampling parameters pre-set in the experiment. The concentration change of the drug in the dissolution medium in the metering solvent bottle can be detected in real time, and the sample can be accurately collected to ensure the stability of sampling, improve the drug detection concentration, and ensure the accuracy of the detection method. At the same time, the solvent capacity in the metering solvent bottle is monitored in real time, and the rehydration component is started to replenish the solvent in the metering solvent bottle to the initial capacity after the solvent capacity is lower than a certain capacity. Dynamic monitoring of the solvent volume can be realized, and timely dynamic rehydration can be achieved to ensure that the solvent volume remains unchanged, thereby improving the accuracy of the detection method. In addition, a jacket layer is provided outside the solvent bottle, and a heat source of suitable temperature is introduced into the jacket to control the temperature of the solvent, thereby ensuring that the solvent and the drug are at the optimal temperature for drug dissolution testing. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG1 is a system block diagram of a closed-loop sampling device for drug dissolution using a circulation cell method provided in one embodiment.

[0023] FIG2 is a schematic diagram of the structure of a closed-loop sampling device for drug dissolution using a circulation cell method provided in one embodiment.

[0024] FIG. 3 is a schematic structural diagram of a solvent bottle cap provided in one embodiment.

[0025] Description of reference numerals:

[0026] 10-metering solvent bottle, 20-circulation pool system, 30-liquid replenishment component;

[0027] 110 - solvent bottle body, 120 - solvent bottle cover, 130 - jacket, 140 - liquid replenishing through hole, 150 - exhaust through hole, 160 - inlet through hole, 170 - outlet through hole, 180 - sampling through hole;

[0028] 131-jacket inlet, 132-jacket outlet;

[0029] 210 - system conduit, 220 - circulation cell, 230 - sampler;

[0030] 211 - inlet conduit, 212 - outlet conduit, 213 - sampling conduit;

[0031] 310- fluid infusion catheter, 320- fluid infusion cup, 330- fluid infusion pump, 340- precision liquid level sensor, 350- fluid infusion controller. DETAILED DESCRIPTION

[0032] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are described in detail below in conjunction with the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present application, so the present application is not limited by the specific embodiments disclosed below.

[0033] In the description of the present application, it should be understood that if the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc. appear, the orientation or position relationship indicated by these terms is based on the orientation or position relationship shown in the accompanying drawings, which is only for the convenience of describing the present application and simplifying the description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present application.

[0034] In addition, if the terms "first" or "second" appear, these terms are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of this application, if the term "plurality" appears, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0035] In this application, unless otherwise clearly specified and limited, if the terms "installed", "connected", "connected", "fixed" and the like appear, these terms should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integrated connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to the specific circumstances.

[0036] In the present application, unless otherwise clearly specified and limited, if there is a description that a first feature is "above" or "below" a second feature, etc., or similar descriptions appear, it may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature being "above", "above" and "above" the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. The first feature being "below", "below" and "below" the second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.

[0037] It should be noted that if an element is referred to as being "fixed to" or "disposed on" another element, it may be directly on the other element or there may be a central element. If an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. If any, the terms "vertical", "horizontal", "upper", "lower", "left", "right" and similar expressions used in this application are for illustrative purposes only and do not represent the only implementation method.

[0038] Referring to FIG. 1 , FIG. 1 shows a system block diagram of a closed-loop sampling device for drug dissolution by a circulation cell method in an embodiment of the present application. The closed-loop sampling device for drug dissolution by a circulation cell method provided in an embodiment of the present application comprises a metering solvent bottle 10, a circulation cell system 20 and a fluid replenishment component 30. The circulation cell system 20 is connected to the metering solvent bottle 10 via a system conduit 210, and the fluid replenishment component 30 is connected to the metering solvent bottle 10 via a fluid replenishment conduit 310. The circulation cell system 20 comprises a circulation cell 220 and a sampler 230.

[0039] Among them, the working principle of the circulation cell system 20 is:

[0040] The experimental sample is placed in the circulation pool 220, and the dissolution medium (usually a simulated physiological fluid, referred to as the solvent in this application) contacts the sample through the circulation pool 220, and the sample gradually dissolves into the medium; then the sampler 230 automatically samples from the dissolution medium containing the sample at a predetermined time point.

[0041] The metering solvent bottle 10 of the circulation cell method drug dissolution closed-loop sampling device includes a solvent bottle body 110 and a solvent bottle cap 120. The solvent bottle cap 120 is arranged at the bottle mouth of the solvent bottle body 110 and is sealed and connected to the solvent bottle body 110 to ensure that the solvent does not leak. The solvent bottle cap 120 includes a system through hole (not shown in the figure) and a fluid infusion through hole 140. The system conduit 210 connected to the circulation cell system 20 passes through the system through hole of the solvent bottle cap 120 to enter the inside of the metering solvent bottle 10, and the fluid infusion conduit 310 connected to the fluid infusion assembly 30 passes through the fluid infusion through hole 140 of the solvent bottle cap 120 to enter the inside of the metering solvent bottle 10. The system conduit 210 is sealed and fitted with the system through hole, and the fluid infusion conduit 310 is sealed and fitted with the fluid infusion through hole 140.

[0042] Refer to FIG. 2 , which shows a schematic diagram of the structure of a closed-loop sampling device for drug dissolution by a circulation cell method in an embodiment of the present application, wherein a jacket 130 is provided on the outside of the solvent bottle 110. The jacket 130 includes a jacket inlet 131 and a jacket outlet 132. When the solvent needs to be heated, a heat source flows in from the jacket inlet 131, flows through the inside of the jacket 130 and flows out from the jacket outlet 132, forming a heat preservation system, controlling the temperature of the solvent, and ensuring that the solvent and the drug are at the optimal temperature for drug dissolution testing.

[0043] After starting the dissolution experiment, the solvent in the metering solvent bottle 10 is discharged into the circulation pool 220 to make the solvent contact with the experimental sample (i.e., the drug). The experimental sample is dissolved into the solvent to obtain the sample solvent (or the solvent to be tested). Then, the sample solvent (i.e., the solvent containing the drug) in the circulation pool 220 is introduced into the metering solvent bottle 10, and this process is repeated continuously to make the solvent in the metering solvent bottle 10 in a flowing state.

[0044] During the process of starting the dissolution experiment, the sample solvent to be tested is extracted from the metering solvent bottle 10 at a set time point, and then the drug concentration test is performed on the extracted sample solvent to be tested. At the same time, during the dissolution experiment, it is necessary to monitor the capacity of the solvent in the metering solvent bottle 10 in real time. Once it is monitored that the capacity of the solvent in the metering solvent bottle 10 is lower than the set value, it is necessary to replenish the solvent to the metering solvent bottle 10 regularly and quantitatively through the rehydration component 30. The frequency and amount of rehydration can be set according to the experimental needs and the solvent consumption.

[0045] In this embodiment, after the metering solvent bottle 10 is connected to the circulation pool system 20 and the fluid replenishment component 30 through the system catheter 210, after the dissolution experiment is started, the solvent to be detected in the metering solvent bottle 10 is driven to circulate between the circulation pool 220 and the metering solvent bottle 10 through the circulation pool 220. During the flow process, the solvent to be detected is contacted with the experimental sample, and the solvent after contacting the experimental sample is stirred in the metering solvent bottle 10. Then, samples are taken from the metering solvent bottle 10 according to the sampling parameters pre-set in the experiment. The concentration change of the drug in the dissolution medium in the metering solvent bottle 10 can be detected in real time, and the sample can be accurately collected to ensure the stability of sampling, improve the drug detection concentration, and ensure the accuracy of the detection method. At the same time, the solvent capacity in the metering solvent bottle 10 is monitored in real time, and the fluid replenishment component 30 is started after the solvent capacity is lower than a certain capacity to replenish the solvent in the metering solvent bottle 10 to the initial capacity. The dynamic monitoring of the solvent volume can be realized, and timely dynamic fluid replenishment can be achieved to ensure that the solvent volume remains unchanged, thereby improving the accuracy of the detection method.

[0046] In an exemplary embodiment, the system through hole includes an inlet through hole 160, an outlet through hole 170 and a sampling through hole 180. The system conduit 210 includes an inlet conduit 211, an outlet conduit 212 and a sampling conduit 213, the inlet conduit 211 and the outlet conduit 212 are both connected to the circulation pool 220, and the sampling conduit 213 is connected to the sampler 230.

[0047] One end of the inlet conduit 211 is connected to the flow outlet (not shown in the figure) of the circulation pool 220, and the other end of the inlet conduit 211 passes through the inlet through hole 160 to enter the interior of the metering solvent bottle 10. One end of the outlet conduit 212 is connected to the flow inlet (not shown in the figure) of the circulation pool 220, and the other end of the outlet conduit 212 passes through the outlet through hole 170 to enter the interior of the metering solvent bottle 10. One end of the sampling conduit 213 is connected to the sampler 230, and the other end of the sampling conduit 213 passes through the sampling through hole 180 to enter the interior of the metering solvent bottle 10.

[0048] The solvent is transferred from the metering solvent bottle 10 to the circulation pool 220 through the outlet conduit 212, and then the solvent contacts the experimental sample in the circulation pool 220 to dissolve the experimental sample, and then the sample solvent is injected into the metering solvent bottle 10 through the inlet conduit 211, and this process is repeated so that the solvent circulates between the circulation pool 220 and the metering solvent bottle 10.

[0049] After the dissolution experiment is carried out for a certain period of time, it is usually necessary to extract a certain amount of sample solvent from the measuring solvent bottle 10 into the sampler 230 through the sampling conduit 213. The sampling conduit 213 is used to extract a certain amount of sample solvent from the measuring solvent bottle 10 at a specific time point or time interval, and transfer it to the sampler 230. After the sampling is completed, the sampling time and sampling amount are recorded in time, and the sample in the sampler 230 is analyzed or stored.

[0050] In an exemplary embodiment, the outlet conduit 212 and the sampling conduit 213 located inside the measuring solvent bottle 10 are both long conduits, and the inlet conduit 211 and the infusion conduit 310 located inside the measuring solvent bottle 10 are both short conduits. The mouth of the long conduit is close to the inner bottom of the measuring solvent bottle 10, and the mouth of the short conduit is close to the bottle mouth of the measuring solvent bottle 10. In one embodiment, the outlet conduit 212 and the sampling conduit 213 are symmetrical about the center of the solvent bottle cap 120, and the inlet conduit 211 and the infusion conduit 310 are symmetrical about the center of the solvent bottle cap 120, and the long conduit and the short conduit are arranged at equal intervals.

[0051] The outlet conduit 212 and the sampling conduit 213 located inside the metering solvent bottle 10 respectively extract the solvent and the sample solvent from the bottom of the metering solvent bottle 10, and the inlet conduit 211 and the rehydration conduit 310 located inside the metering solvent bottle 10 respectively transport the sample solvent and the solvent to the inside of the metering solvent bottle 10 near the bottle mouth.

[0052] In this embodiment, by extending the long conduit to the bottom of the solvent bottle 110 and connecting the short conduit to the inlet of the metering solvent bottle 10, the flow path of the solvent or sample solvent is controlled, which effectively reduces the interference of mutual concentrations during the circulation process and improves the accuracy and reliability of the solubility detection of the sample solvent in the metering solvent bottle 10.

[0053] In an exemplary embodiment, the solvent bottle cap 120 further includes an exhaust hole 150 .

[0054] During the solvent circulation process, it is very important to ensure the balance between the internal pressure and the external pressure of the measuring solvent bottle 10. If the two are inconsistent, it may lead to the inability to circulate the solvent between the measuring solvent bottle 10 and the circulation pool 220, or it may be impossible to accurately extract a certain volume of sample solvent from the measuring solvent bottle 10. Therefore, the exhaust through hole 150 is provided on the solvent bottle cap 120 to balance the internal pressure and the external pressure of the measuring solvent bottle 10.

[0055] In addition, an exhaust baffle may be provided at the exhaust hole 150, and the exhaust baffle may be provided with a number of evenly distributed small holes, which may reduce the dust in the air from entering the metering solvent bottle 10, thereby improving the accuracy of the sample solvent detection concentration, i.e., the dissolution rate.

[0056] In this embodiment, the design of the exhaust hole 150 and the exhaust baffle can ensure the pressure balance inside and outside the metering solvent bottle 10, ensure the smooth circulation of the solvent and the sampling operation, and at the same time maintain the purity of the solvent and the accuracy of the experimental data, thereby improving the stability and reliability of the experiment and providing reliable data support for the evaluation of the dissolution performance of the drug.

[0057] Continuing to refer to FIG. 2 , in some embodiments, the rehydration assembly 30 of the closed-loop sampling device for drug dissolution by the circulation cell method includes a rehydration cup 320 , which is connected to a rehydration catheter 310 and is connected to a metering solvent bottle 10 through the rehydration catheter 310 , and a rehydration pump 330 is also provided on the rehydration catheter 310 .

[0058] One end of the infusion conduit 310 extends to the inside of the infusion cup 320 , and the other end of the infusion conduit 310 passes through the infusion through hole 140 of the solvent bottle cover 120 and extends to the inside of the metering solvent bottle 10 .

[0059] In addition, the rehydration component 30 further includes a precision liquid level sensor 340 , which is disposed at the end of the rehydration conduit 310 located inside the metering solvent bottle 10 , and a rehydration controller 350 is connected between the precision liquid level sensor 340 and the rehydration pump 330 .

[0060] During the dissolution experiment, the sampler 230 extracts the sample solvent to be tested from the metering solvent bottle 10 at a set time point. After a certain number of sample extractions, the volume of the liquid (i.e., the sample solvent) in the metering solvent bottle 10 decreases. When the liquid level in the metering solvent bottle 10 is lower than the set value of the precision liquid level sensor, the precision liquid level sensor transmits a signal to the liquid replenishment controller 350, and the liquid replenishment controller 350 controls the liquid replenishment pump 330 to start. After the liquid replenishment pump 330 is started, the solvent in the liquid replenishment cup 320 is transported to the metering solvent bottle 10 through the liquid replenishment conduit 310 until the liquid level of the liquid in the metering solvent bottle 10 reaches the set value of the precision liquid level sensor.

[0061] In an exemplary embodiment, the measuring solvent bottle 10 further includes a stirring device (not shown in the figure). The stirring device can evenly stir the liquid in the measuring solvent bottle 10 to ensure that the medicine in the solvent containing the medicine is fully dissolved and evenly distributed in the measuring solvent bottle 10. The stirring device can be a magnetic stirring bar or a mechanical stirring device, and the magnetic stirring bar is the preferred stirring device.

[0062] In an exemplary embodiment, the scale representing the corresponding solvent volume is marked on the outer wall of the solvent bottle 110 of the measuring solvent bottle 10. In one embodiment, the maximum scale of the measuring solvent bottle 10 is set to 50 milliliters. Reducing the solvent volume can increase the concentration of medicine in the sample, thereby improving the sensitivity and accuracy of detection. Meanwhile, reducing the solvent volume can reduce the influence of background interfering substances, making the test result clearer and more reliable. In addition, reducing the solvent volume also helps to save costs and improve detection efficiency, because less solvent means less waste liquid treatment and shorter analysis time.

[0063] In an exemplary embodiment, a closed-loop sampling device for drug dissolution by a circulation cell method is provided. The closed-loop sampling device for drug dissolution by a circulation cell method comprises a metering solvent bottle 10, a circulation cell system 20 and a fluid infusion component 30, wherein the metering solvent bottle 10 is connected to the circulation cell system 20 via a system conduit 210, and the metering solvent bottle 10 is also connected to the fluid infusion component 30 via a fluid infusion conduit 310. The metering solvent bottle 10 adopts a bottle with a maximum volume of 50 ml.

[0064] The measuring solvent bottle 10 comprises a solvent bottle body 110, a solvent bottle cap 120 and a stirring device, wherein the solvent bottle cap 120 is arranged at the bottle mouth of the solvent bottle body 110, and the solvent bottle cap 120 is sealed and connected with the solvent bottle body 110. The solvent bottle cap 120 comprises an inlet through hole 160, an outlet through hole 170, a sampling through hole 180, a liquid infusion through hole 140 and an exhaust through hole 150, and the exhaust through hole 150 is covered with an exhaust baffle, and the exhaust baffle is provided with a plurality of evenly distributed pores. The stirring device can adopt a magnetic stirring bar or a mechanical stirring device, and the magnetic stirring bar is a preferred stirring device.

[0065] The circulation cell system 20 includes a circulation cell 220 and a sampler 230. The system conduit 210 includes an inlet conduit 211, an outlet conduit 212 and a sampling conduit 213. One end of the inlet conduit 211 and one end of the outlet conduit 212 are respectively connected to the circulation outlet and the circulation inlet of the circulation cell 220, and the other end of the inlet conduit 211 and the other end of the outlet conduit 212 pass through the inlet through hole 160 and the outlet through hole 170 of the solvent bottle cap 120, respectively, and the other end of the inlet conduit 211 and the other end of the outlet conduit 212 both extend to the inside of the metering solvent bottle 10. One end of the sampling conduit 213 is connected to the sampler 230, and the other end of the sampling conduit 213 passes through the sampling through hole 180 of the solvent bottle cap 120, and the other end of the sampling conduit 213 extends to the inside of the metering solvent bottle 10. Among them, the parts of the outlet conduit 212 and the sampling conduit 213 extending into the interior of the measuring solvent bottle 10 are both long conduits, and the tube mouths of the long conduits are close to the inner bottom of the measuring solvent bottle 10; the part of the inlet conduit 211 extending into the interior of the measuring solvent bottle 10 is a short conduit, and the tube mouth of the short conduit is located below the solvent liquid level in the measuring solvent bottle 10 and close to the liquid surface.

[0066] The rehydration assembly 30 includes a rehydration cup 320, a rehydration pump 330, a liquid level sensor and a rehydration controller. The rehydration cup 320 is connected to the metering solvent bottle 10 through a rehydration conduit 310, and the rehydration pump 330 is arranged on the rehydration conduit 310. One end of the rehydration conduit 310 extends to the inside of the rehydration cup 320, and the other end of the rehydration conduit 310 extends to the inside of the solvent bottle 10 through the rehydration through hole 140 of the solvent bottle cover 120. The liquid level sensor is arranged at the port of the rehydration conduit 310 located inside the solvent bottle 10, and a rehydration controller is connected between the liquid level sensor and the rehydration pump 330. Among them, the part of the rehydration conduit 310 extending to the inside of the solvent bottle 10 is a short conduit, and the pipe mouth of the short conduit is located below the liquid level of the solvent in the metering solvent bottle 10 and close to the liquid level.

[0067] Refer to Figure 3, which shows a schematic diagram of the structure of the solvent bottle cap 120 in an embodiment of the present application. The exhaust through hole 150 is located at the center of the solvent bottle cap 120, and the long conduit and the short conduit are respectively located on the diagonal line, that is, a long conduit and a short conduit are symmetrically arranged about the exhaust through hole 150. In one embodiment, as shown in Figure 3, the sampling through hole 180 and the fluid infusion through hole 140 are symmetrically arranged about the exhaust through hole 150, and the inlet through hole 160 and the outlet through hole 170 are symmetrically arranged about the exhaust through hole 150. Correspondingly, the sampling conduit 213 passing through the sampling through hole 180 and the fluid infusion conduit 310 passing through the fluid infusion through hole 140 are symmetrically arranged about the exhaust through hole 150, and the inlet conduit 211 passing through the inlet through hole 160 and the outlet conduit 212 passing through the outlet through hole 170 are symmetrically arranged about the exhaust through hole 150.

[0068] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0069] The above-described embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be construed as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent application shall be subject to the attached claims.

Claims

1. A closed-loop sampling device for drug dissolution by a circulation cell method, characterized in that: The closed-loop sampling device for drug dissolution by the circulation cell method comprises: Measuring solvent bottle, used to prepare and hold the solvent to be tested, and monitor the volume of the solvent; A circulation cell system, connected to the metering solvent bottle through a system conduit, used for circulating the solvent to be tested in the metering solvent bottle during the circulation cell dissolution test and sampling during the circulation cell test, including a circulation cell and a sampler; A fluid replenishment component, connected to the metering solvent bottle via a fluid replenishment conduit, and used for timely and quantitatively replenishing the solvent in the metering solvent bottle; The metering solvent bottle comprises a solvent bottle body and a solvent bottle cap, wherein the solvent bottle cap is sealed and connected to the solvent bottle body, and the solvent bottle cap comprises a system through hole and a fluid infusion through hole; the system through hole is used to accommodate a system conduit connected to the circulation pool system; the fluid infusion through hole is used to accommodate a fluid infusion conduit connected to the fluid infusion assembly; A jacket is arranged outside the solvent bottle body, and the jacket is used to pass a heat source and utilize the heat source to perform timed heating and temperature control on the solvent.

2. The closed-loop sampling device for drug dissolution by a circulation cell method according to claim 1, characterized in that: The system through hole comprises an inlet through hole, an outlet through hole and a sampling through hole, and the system conduit comprises an inlet conduit, an outlet conduit and a sampling conduit; One end of the inlet conduit is connected to the flow outlet of the circulation pool, and the other end of the inlet conduit passes through the inlet through-hole. One end of the outlet conduit is connected to the flow inlet of the circulation pool, and the other end of the outlet conduit passes through the outlet through-hole. One end of the sampling conduit is connected to the sampler, and the other end of the sampling conduit passes through the sampling through-hole.

3. The closed-loop sampling device for drug dissolution by a circulation cell method according to claim 2, characterized in that: The portion of the outlet conduit located inside the measuring solvent bottle and the portion of the sampling conduit located inside the measuring solvent bottle are both long conduits, and the tube mouths of the long conduits are close to the inner bottom of the measuring solvent bottle. The portion of the inlet conduit located inside the measuring solvent bottle and the portion of the rehydration conduit located inside the measuring solvent bottle are both short conduits, and the tube mouths of the short conduits are located below the liquid level of the solvent in the measuring solvent bottle and close to the liquid surface.

4. The closed-loop sampling device for drug dissolution by a flow cell method according to claim 3, characterized in that: The outlet conduit and the inlet conduit are symmetrically arranged about the center of the solvent bottle cap, the infusion conduit and the sampling conduit are symmetrically arranged about the center of the solvent bottle cap, and the long conduit and the short conduit are equidistantly arranged.

5. The closed-loop sampling device for drug dissolution by a circulation cell method according to claim 1, characterized in that: The solvent bottle cap also includes an exhaust through hole, and the exhaust through hole is used to balance the internal pressure and external pressure of the measuring solvent bottle.

6. The closed-loop sampling device for drug dissolution by the circulation cell method according to claim 5, characterized in that: The exhaust through hole is covered with an exhaust baffle, and a plurality of evenly distributed small holes are arranged on the exhaust baffle. The exhaust baffle is used to reduce the dust from entering the solvent bottle during long-term testing.

7. The closed-loop sampling device for drug dissolution by a flow cell method according to claim 1, characterized in that: The fluid infusion component includes a fluid infusion cup, which is connected to the fluid infusion catheter, and a fluid infusion pump is arranged on the fluid infusion catheter.

8. The closed-loop sampling device for drug dissolution by a flow cell method according to claim 7, characterized in that: The fluid infusion component also includes a precision liquid level sensor, which is arranged at the fluid infusion catheter port located inside the solvent bottle, and a fluid infusion controller is connected between the precision liquid level sensor and the fluid infusion pump.

9. The closed-loop sampling device for drug dissolution by a flow cell method according to claim 1, characterized in that: The solvent bottle also includes a stirring device, which is used to apply stirring force to the solvent in the solvent bottle and maintain uniform distribution of the medicine in the solvent.

10. The closed-loop sampling device for drug dissolution by a circulation cell method according to claim 1, characterized in that: The outer wall of the solvent bottle of the measuring solvent bottle is marked with scales indicating the corresponding solvent volume.

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