WO2021163988A1

WO2021163988A1 - Dissolution testing auxiliary apparatus

Info

Publication number: WO2021163988A1
Application number: PCT/CN2020/076129
Authority: WO
Inventors: 王立坤; 顾国祥; 张凤娥
Original assignee: 南京海维医药科技有限公司
Priority date: 2020-02-21
Filing date: 2020-02-21
Publication date: 2021-08-26
Also published as: CN111356919A

Abstract

A dissolution testing auxiliary apparatus. The apparatus comprises an absorption part (110) and an adjustment part (120), the absorption part (110) comprises an absorption unit (111-1), and the adjustment part (120) comprises an adjustment unit (125); the absorption part (110) is in communication with a dissolution vessel (130) by means of a first pipeline (112); the adjustment part (120) is in communication with the dissolution vessel (130) by means of a second pipeline (121) and a third pipeline (122); a first liquid inlet pump (113), a second liquid inlet pump (123), and a first liquid outlet pump (124) are respectively arranged on the first pipeline (112), the second pipeline (121), and the third pipeline (122); the first liquid inlet pump (113) guides a dissolution liquid to the absorption part (110) by means of the first pipeline (112), the guided dissolution liquid flows into the absorption unit (111-1), the second liquid inlet pump (123) guides the dissolution liquid into the adjustment part (120) by means of the second pipeline (121), the adjustment unit (125) adjusts the pH and/or the volume of the guided dissolution liquid, and the first liquid outlet pump (124) guides the adjusted dissolution liquid back to the dissolution vessel (130). Utilizing a means such as filtering or liquid-liquid extraction in combination with in vivo pH change conditions emulates a specific process of absorption of a drug within a body, increasing the accuracy of measurement results by the dissolution apparatus.

Description

Auxiliary device for dissolution test

Technical field

This application relates to the field of drug testing equipment, in particular, to a dissolution test auxiliary device that simulates drug absorption.

Background technique

Dissolution rate refers to the rate and extent of the dissolution of active pharmaceutical ingredients from tablets, capsules or granules under prescribed conditions. Dissolution devices, such as dissolution apparatus, are used to check the rate and extent of dissolution of pharmaceutical tablets or capsules in prescribed solvents. The amount of solvent used in the current dissolution device is quite different from the actual gastric juice or intestinal juice in the human body, and the existing dissolution device cannot reflect the actual amount of gastric juice and intestinal juice in the human body. In addition, the dissolution device generally dissolves the drug by adding a surfactant to the solvent. In the process of dissolving the drug, it is often assumed that the drug has been absorbed, but the human body is a process of dissolving and absorbing the drug, and dissolving and absorbing The time is related to the characteristics of the drug and the internal environment of the human body. In addition, the solubility of drugs, especially weakly basic drugs, will vary under different conditions during the specific administration process. Different pH conditions result in different solubility of the drug, and drug precipitation may occur. Therefore, there is a need for a device that can further simulate the dissolution and absorption of simulated drugs in the human body in order to accurately evaluate the laws of drug dissolution and absorption.

Summary of the invention

An aspect of the present application provides an auxiliary device for dissolution testing. The device includes an absorption part and an adjustment part, wherein the absorption part includes an absorption unit, the adjustment part includes an adjustment unit, and the absorption part passes through a first The pipe is in communication with the dissolution cup of the drug dissolution device; the adjustment part is in communication with the dissolution cup through the second pipe and the third pipe; the first pipe, the second pipe and the third pipe are respectively provided with a first liquid inlet A pump, a second liquid inlet pump, and a first liquid outlet pump; wherein the first liquid inlet pump is configured to introduce the eluent in the dissolution cup into the absorption part through the first pipe, and the The dissolution liquid flows into the absorption unit; the second liquid inlet pump is configured to introduce the dissolution liquid in the dissolution cup into the regulating part through the second pipe, and the regulating unit is configured to regulate the introduced For the pH and/or volume of the dissolution liquid, the first liquid pump is configured to lead the adjusted dissolution liquid back to the dissolution cup.

In some embodiments, the absorption unit includes a liquid trap, and the liquid trap is capable of collecting the eluent flowing in from the first pipe.

In some embodiments, the liquid trap is connected to an analysis device that can analyze the eluate collected by the liquid trap.

In some embodiments, the device further includes a fourth pipe that communicates with the absorption unit and the dissolution cup. After at least part of the dissolution liquid flowing into the absorption unit flows out, it passes through the fourth pipe. Flow back into the dissolution cup.

In some embodiments, the absorption unit includes a membrane filter configured to collect the dissolved medicine and/or part of the dissolving liquid in the dissolving liquid flowing in from the first pipe.

In some embodiments, the absorption unit includes a liquid-liquid extractor configured to collect the medicine dissolved in the dissolving liquid flowing in from the first pipe; the fourth pipe is provided with a A second liquid outlet pump, the second liquid outlet pump is configured to lead the dissolution liquid from which the medicine has been extracted back to the dissolution cup through the fourth pipe.

In some embodiments, the adjusting unit includes at least one pH adjusting substance storage bin, which is communicated with the inside of the adjusting part through an adjusting pipe, and is used for adding adjusting substances to the dissolving liquid flowing through the adjusting part to adjust the dissolving liquid.的pH.

In some embodiments, different pH adjusting substance storage bins contain different adjusting substances for adding different adjusting substances to the eluent flowing through the adjusting part in different time periods.

In some embodiments, the adjusting substance includes at least one of the following: carbon dioxide gas, argon gas, nitrogen gas, helium gas, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer Solution, tris buffer, barbiturate buffer, phthalate buffer, ammonia-ammonium vaporized buffer, and boric acid buffer.

In some embodiments, a flow pump is provided on the regulating pipe, which is configured to limit the amount and/or flow rate of the regulating substance added.

In some embodiments, the adjustment part further includes a dissolution medium supplement unit, which communicates with the inside of the adjustment part through a supplementary pipe, and is used to add a liquid The dissolution medium that dissolves the drug.

In some embodiments, a flow pump is provided on the supplementary pipeline, and is configured to limit the amount and/or flow rate of the dissolution medium added for control.

In some embodiments, the device further includes at least one pH detection unit, which is disposed inside the adjusting part and/or inside the dissolution cup or on the third pipe, and is configured to detect the pH value of the dissolution liquid.

In some embodiments, the device further includes a control device that communicates with a pump in the device through an electrical connection and/or a wireless connection, and is configured to control the pump to adjust the amount and/or flow rate of the solution passing through the pump.

In some embodiments, the device further includes a constant temperature unit for preheating and/or maintaining the absorption part and/or the adjustment part.

Another aspect of the present application provides an auxiliary device for dissolution testing. The device includes an absorption part and an adjustment part, wherein the absorption part includes a shunt valve and an absorption unit, and the adjustment part includes an adjustment unit; The first pipe communicates with the dissolution cup of the drug dissolution device, and the second pipe communicates with the adjusting portion; the adjusting portion communicates with the dissolution cup through a third pipe; the first pipe and the third pipe The pipeline is provided with an inlet pump and an outlet pump respectively; wherein, the diverting valve is placed on the first pipeline to divide the dissolution liquid from the dissolution cup through the inlet pump, and a part of the dissolution liquid flows into In the absorption unit, another part of the eluate flows into the adjustment part; the adjustment unit of the adjustment part is configured to adjust the pH of the eluate flowing into the adjustment part, and the discharge pump is configured to adjust the pH of the The dissolution liquid is led back to the dissolution cup.

In some embodiments, the absorption unit includes a liquid trap, and the liquid trap is capable of collecting a portion of the eluate that is diverted from the diverting pump.

In some embodiments, the adjustment unit includes at least one pH adjustment substance storage bin, which is communicated with the inside of the adjustment part through an adjustment pipe, and is used to add adjustment substances to the eluent flowing through the adjustment part to adjust the The pH of the dissolution liquid.

In some embodiments, the adjusting substance includes at least one of the following: carbon dioxide gas, argon gas, nitrogen gas, helium gas, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer , Tris buffer, barbital buffer, phthalate buffer, ammonia-ammonium vaporized buffer, and boric acid buffer.

In some embodiments, the device further includes at least one pH detection unit, which is disposed inside the adjustment part and/or inside the dissolution cup, and is configured to detect the pH value of the dissolution liquid.

In some embodiments, the device further includes a constant temperature unit for preheating and/or maintaining the absorption part and/or the adjustment part. It is used to preheat and/or keep the absorption chamber, the adjustment part and/or the dissolution cup.

Description of the drawings

This application will be further described in the form of exemplary embodiments, and these exemplary embodiments will be described in detail with the accompanying drawings. These embodiments are not restrictive. In these embodiments, the same number represents the same structure, in which:

Figure 1 is a schematic structural diagram of a dissolution test auxiliary device according to some embodiments of the present application;

2 is a schematic structural diagram of a dissolution test auxiliary device that uses membrane filtration to simulate absorption according to some embodiments of the present application;

FIG. 3 is a schematic structural diagram of a dissolution test auxiliary device that uses an extraction method to simulate absorption according to some embodiments of the present application;

Fig. 4 is another structural schematic diagram of the dissolution test auxiliary device according to some embodiments of the present application.

Detailed ways

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following will briefly introduce the drawings that need to be used in the description of the embodiments. Obviously, the drawings in the following description are only some examples or embodiments of the application. For those of ordinary skill in the art, without creative work, the application can be applied to the application according to these drawings. Other similar scenarios. Unless it is obvious from the language environment or otherwise stated, the same reference numerals in the figures represent the same structure or operation.

As shown in the present application and claims, unless the context clearly suggests exceptional circumstances, the words "a", "an", "an" and/or "the" do not specifically refer to the singular, but may also include the plural. Generally speaking, the terms "include" and "include" only suggest that the clearly identified steps and elements are included, and these steps and elements do not constitute an exclusive list, and the method or device may also include other steps or elements.

This application describes various embodiments of the dissolution test auxiliary device. It should be understood that the present invention is not limited to the specific embodiments described herein, and may be adjusted, modified, and/or changed. The solution described in conjunction with a specific embodiment is not necessarily limited to this embodiment and can be implemented in any other solution. For example, although the various embodiments are described in conjunction with the dissolution apparatus, it should be understood that the present invention can also be implemented in other test equipment, such as any other test equipment and/or device that can achieve the purpose of dissolution detection. It should also be understood that the terminology used herein is only for the purpose of describing specific embodiments and is not intended to be limiting, as the scope of the present invention will be defined by the appended claims together with equivalents giving the full scope of these claims. In addition, various embodiments are described with reference to the drawings. It should be noted that the drawings are not drawn on a scale, and are only intended to facilitate the description of specific implementations. The drawings are not intended to be an exhaustive description or to limit the scope of the invention.

In order to facilitate the description of the relative position, direction or spatial relationship in conjunction with the accompanying drawings, this text may use terms such as "upper", "above", "above", "above", "above", "below", "below", Various relative terms such as "bottom", "higher", "lower" or similar terms. For ease of describing some embodiments, the term "level" or "upper or lower level" may be used. The use of relative terms should not be construed as implying the orientation, orientation, or structure or part of it necessary for manufacture or use, and should not It is construed to limit the scope of the present invention. As used in the specification and appended claims, unless the context clearly indicates otherwise, the singular forms "a", "an" and "said" may include multiple referents. For example, the reference to "direction" may include the opposite direction of the direction and multiple directions parallel to the direction.

Fig. 1 is a schematic structural diagram of a dissolution test auxiliary device according to some embodiments of the present application. As shown in FIG. 1, the dissolution test auxiliary device may include an absorption part 110 and an adjustment part 120. Wherein, the absorption part 110 may refer to a component used to simulate the digestive tract (for example, stomach, intestine) of the body to absorb and collect drugs, and reflect the absorption of the drug by simulating the absorption process of the digestive tract of the body. The absorption situation may include the amount or concentration value of the substance that absorbs the drug at different time points or/and different pH environments. For example, a drug is placed in the dissolution solution of the dissolution cup 130 for dissolution, 30 minutes after the start of dissolution, the absorption process of the small intestine is simulated by the absorption part 110, and the amount or amount of the drug in the dissolution solution of the absorption part 110 is measured at this time. The drug concentration can reflect the absorption of the drug. The absorption part 110 may include an absorption unit 111-1, and the absorption unit 111-1 refers to a component used to simulate the digestive tract (for example, stomach, intestine) of the body to absorb medicine.

The adjusting part 120 may be a component for simulating the environment corresponding to the medicine in different parts of the body. The corresponding environment in different parts of the body may include the pH of the body fluid, the amount of the body fluid, or the components in the body fluid, or any combination thereof. As an example, for example, under normal circumstances, the pH value of gastric juice in the human stomach generally ranges from 1.3 to 1.8. After a meal, the pH value of the gastric juice can rise to 3.5 when the gastric juice is diluted, and the pH of the small intestine juice in the human small intestine is about 8-9. In this embodiment, the pH value of various parts of the body can be simulated by changing the pH value of the eluate in the adjusting part 120. In some embodiments, the adjusting part 120 may include an adjusting unit 125, and the adjusting unit 125 may be used to adjust the pH and/or volume of the eluent introduced into the adjusting part 120. The adjusting part 120 can be a cuboid, cylindrical, cone-shaped or irregular container. The material of the adjusting part 120 can be selected from amorphous inorganic non-metallic materials (glass), polyethylene (PE), polypropylene (PP), poly Styrene (PS), polyvinyl chloride (PVC), acrylonitrile-butadiene-styrene copolymer (ABS), polyethylene terephthalate (PET) or polybutylene terephthalate (PBT) ).

The absorption part 110 is in communication with the dissolution cup 130 of the drug dissolution device through the first pipe 112. A first liquid inlet pump 113 is provided on the first pipe 112, and the first liquid inlet pump 113 is configured to dissolve the dissolution liquid The absorption part 110 is introduced through the first pipe 112, and the introduced eluate flows into the absorption unit 111-1. In some embodiments, the first pipe 112 may be a soft pipe or a hard pipe, and the first pipe 112 may be selected from metal pipes (such as steel pipes, stainless steel pipes, etc.), plastic-clad metal pipes (such as aluminum-plastic composite pipes), and plastic pipes. Pipes (such as PVC pipes, UPVC pipes, PE pipes, etc.). In some embodiments, the first feed pump 113 may include at least any one of a peristaltic pump, a centrifugal pump, a circulating pump, and a jet pump.

In some embodiments, the connection between the first pipe 112 and the dissolution cup 130 and the absorption part 110 is not limited to the two ends of the first pipe 112 shown in FIG. 1 directly extending into the dissolution cup 130 and the absorption part 110. Way. In some embodiments, the top of the dissolution cup 130 and the top of the absorption part 110 may be provided with a corresponding top plate (not shown in the figure). The top plate is provided with an orifice for the first pipe 112 to extend into. A corresponding fixing member may be provided to fix the first pipe 112. In some embodiments, the fixing member can be a bolt with a through hole. The end of the first pipe 112 can pass through the through hole of the bolt and extend into the dissolution cup 130 or the absorption part 110. The first pipe can be adjusted by twisting the bolt. The height of the end of the pipe 112. In some embodiments, the fixing member can also be a rubber plug with a through hole, and the height of the end of the first pipe 112 can be adjusted by external force acting on it. In some embodiments, the fixing member may also be a clamping piece (such as a clamp), which is fixed on the top plate, and the height of the end of the first pipe 112 can be adjusted by controlling the tightness of the clamping piece.

In some embodiments, the connection between the first pipe 112 and the dissolution cup 130 and the absorption part 110 is not limited to the vertical insertion shown in FIG. 1 from top to bottom. One end of the first pipe 112 may be The side walls of the dissolution cup 120 or the absorption part 110 are connected to achieve communication, and the other end can be inserted into the dissolution cup 120 or the absorption part 110 from top to bottom in the vertical direction, or the two ends of the first pipe 112 are connected to the dissolution cup respectively. The cup 120 and the side walls of the absorbing part 110 are connected to achieve communication. The end of the first pipe 112 located in the dissolution cup 120 is below the liquid surface, and the end of the first pipe 112 located in the absorption part 110 may be above the liquid surface or below the liquid surface.

The adjusting part 120 communicates with the dissolution cup 130 through the second pipe 121 and the third pipe 122. Among them, the second pipe 121 and the third pipe 122 are two independent pipes. The two ends of the second pipe 121 are respectively located in the regulating part 120 and the dissolution cup 130, and the two ends of the third pipe 122 are respectively located in the regulating part. 120 and the dissolution cup 130. Further, the second pipe 121 is provided with a second liquid inlet pump 123, and the third pipe 122 is provided with a first liquid outlet pump 124. Wherein, the second liquid inlet pump 123 is configured to introduce the eluate in the dissolution cup 130 into the adjusting part 120 through the second pipe 121, and the adjusting unit 125 is configured to adjust the pH and/or volume of the introduced eluate. A liquid pump 124 is configured to guide the adjusted dissolution liquid back to the dissolution cup 130. It should be noted here that the type of the second pipe 121 and the third pipe 122 can refer to the first pipe 112, the connection mode between the second pipe 121 and the adjusting part 120 and the dissolution cup 130, and the third pipe 122 and the adjusting part. 120 and the dissolution cup 130 can refer to the connection between the first pipe 112 and the dissolution cup 130 and the absorption part 110, and the type of the second inlet pump 123 and the first outlet pump 124 can refer to the first inlet The liquid pump 113 will not be described in detail here. In addition, the end of the second pipe 121 located at the dissolution cup 130 is below the liquid level in the dissolution cup 130, and the end of the second pipe 121 located at the regulating part 120 may be above the liquid level in the regulating part 120, It may also be below the liquid level in the adjustment part 120. The third pipe 122 located at the end of the dissolution cup 130 can be above the liquid level in the dissolution cup 130 or below the liquid level in the dissolution cup 130. The third pipe 122 is located at the end of the regulating part 120 at the regulating part. Below the liquid level in 120.

In some embodiments, the first pipe 112 and the first liquid inlet pump 113 may be included in the absorption unit 111-1. The absorption unit 111-1 refers to a component used to simulate the digestive tract (such as stomach and intestine) of the body to absorb drugs. In this embodiment, the first pipe 112 and the first liquid inlet pump 113 remove the dissolution cup 130. The eluate containing the medicine is introduced into the absorption part and flows into the absorption unit. In this process, the first pipe 112 and the first liquid inlet pump 113 play a role in simulating the collective digestive tract to absorb the medicine.

In some embodiments, the first pipe 112 may also be provided with a filter part, and the filter part may include at least one filter head or a filter screen. The filter head or the filter screen may be installed at the end of the first pipe 112 in the dissolution cup 130, and the filter screen may be installed in the pipe of the first pipe 112. In some embodiments, the specifications of the filter head or/and the filter screen (such as mesh number, wire diameter, pore size) can be selected according to the molecular weight of the drug and experimental requirements. The filter head or/and the filter screen of the filter screen can be selected from stainless steel, nickel, copper, polypropylene, acrylonitrile-butadiene-styrene copolymer, polytetrafluoroethylene, polyethersulfone, mixed cellulose ester, nylon, poly It is made of vinylidene fluoride and other materials. In addition, those skilled in the art know that the filter screen can be selected according to the pH value of the eluent. For example, when the eluent is acidic or alkaline, a filter with higher corrosion resistance should be selected. In some embodiments, the filtering part may further include a Caco-2 monolayer cell membrane or animal (for example, rat) isolated intestinal tube. The filtering part can prevent the undissolved medicine in the dissolution cup 130 from entering the absorption part 110 and improve the accuracy of the detection result.

In some embodiments, the second pipe 121 and the third pipe 122 may also be provided with filtering parts. The filter head or the filter screen can be installed in the end of the second pipe 121 located in the dissolution cup 130 and the end of the third pipe 122 located in the regulating part 120, and the filter screen can be installed in the pipes of the second pipe 121 and the third pipe 122 . For the specific description of the filtering part in this paragraph, please refer to the filtering part in the above-mentioned first pipe 112, which will not be detailed here.

In some embodiments, the absorption unit 111-1 includes a liquid trap that can collect the eluent flowing in from the first pipe 112. The liquid trap may refer to a container used to collect the dissolution liquid. The liquid trap may include one or more containers (not shown in Figure 1). For example, the number of containers may be one, two, three, or four. or more. When the liquid trap contains multiple containers, the eluate can be collected separately at different time points. In some embodiments, multiple containers may be placed in a single row, multiple rows, or irregularly. Single-row placement means that multiple containers are placed one after the other in a horizontal or vertical row. Multi-row placement means that multiple containers are divided into multiple rows (for example, two rows, three rows, etc.). When the containers are placed in multiple rows, the number of containers between the rows may be the same or different. Irregular placement means that the containers are not arranged in vertical or horizontal rows, but arranged in a circumferential direction or irregular shapes. In some embodiments, the number of the first pipe 112 may be one or more. When the number of the first pipe 112 is one and the container in the liquid collector is one, the first liquid inlet pump 113 can introduce the dissolution liquid in the dissolution cup 130 into a specific container. When the number of the first pipe 112 is one and there are multiple containers in the liquid collector, the position of the container can be adjusted manually or mechanically so that the end of the first pipe 112 is directly above the corresponding container. When the number of the first pipes 112 is multiple, the multiple first pipes 112 may be located just above the multiple containers, so as to collect multiple sample solutions at the same time.

In some embodiments, the liquid trap is connected to an analysis device, and the analysis device can analyze the eluate collected by the liquid trap. Analysis equipment can include balance, acidity meter, conductivity meter, automatic positioning titrator, permanent stop titrator, Karl Fischer moisture analyzer, high performance liquid chromatograph, visible spectrophotometer, ultraviolet-visible spectrophotometer, atomic absorption Any one or more of spectrophotometer, colorimeter, gas chromatograph, polarimeter, sugar meter. The liquid trap and analysis equipment can be connected through corresponding pipelines. For example, the liquid trap and the high performance liquid chromatograph can be connected through the pipeline. The acidity meter, conductivity meter, sugar meter, etc. can be directly placed in the liquid trap, and the balance can be directly connected. Place it under the liquid trap.

In some embodiments, the adjusting unit 125 may include at least one pH adjusting substance storage bin, which is communicated with the inside of the adjusting part 120 through the adjusting pipe 125-1, and is used to add adjusting substances to the dissolution liquid flowing through the adjusting part 120 to adjust the dissolution. The pH of the liquid. The pH adjusting substance storage bin refers to a container for holding the adjusting substance. The pH adjusting substance storage bin may include one or more, and different pH adjusting substance storage bins may contain the same or different adjusting substances. The adjusting substance may be used to adjust the pH value of the dissolving liquid in the adjusting part 120, and the adjusting substance may include any one of gas, liquid, or solid. The pH adjusting substance storage bin is not limited to being located outside the adjusting part 120 as shown in FIG. 1, and it may also be located inside the adjusting part 120. As an example, the adjusting part 120 is a closed structure or a top plate is provided on the top of the adjusting part 120, the pH adjusting substance storage bin may be fixed on the top of the adjusting part 120, and the fixing method may include any one of welding, riveting, and bonding. kind.

In some embodiments, different pH adjusting substance storage bins may contain different adjusting substances for adding different adjusting substances to the eluent flowing through the adjusting part in different time periods. The adjusting part 120 is used to imitate the pH changes of various parts of the body. The circulation time of the drug in the entire device can be regarded as the action time in the body. As time goes by, the part of the drug in the body will also change. , That is, the environment in which the drug is located has also changed, which can be specifically reflected in the pH value and/or regulating substances in the body fluid. The pH adjustment substance storage bin can be used to adjust the pH value of the dissolution liquid in the adjustment part 120 on the one hand, and on the other hand, it can change the adjustment substance contained in the dissolution liquid in the adjustment part 120 to further improve the simulation degree of the drug being dissolved and absorbed. As an example, the change of the pH value of the drug in the human digestive tract over time is known, and the pH value and the adjusting substance in the adjusting part 120 are adjusted according to the pH change in these known time periods. Regarding the connection between the adjusting pipe 125-1 and the adjusting part 120 and the material of the adjusting pipe 125-1, please refer to the specific description between the first pipe 112 and the dissolution cup 130 or the absorption part 110, which will not be described in detail here.

In some embodiments, the regulating substance includes at least one of the following: carbon dioxide gas, argon gas, nitrogen gas, helium gas, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer, three Hydroxymethylaminomethane buffer, barbital buffer, phthalate buffer, ammonia-vaporized ammonium buffer and boric acid buffer. It should be pointed out that the regulating substances in the specification of this application are not limited to the contents listed above. The function of the regulating substance is to regulate the pH value of the dissolution liquid. Any substance that can achieve this function can be a regulating substance. The selection of the regulating substance It can be determined according to specific experiments, and is not further limited here.

In some embodiments, the regulating pipe 125-1 is provided with a flow pump 125-2 configured to limit the amount and/or flow rate of the regulating substance added. The flow pump 125-2 can set the corresponding flow rate, and the corresponding flow rate can be calculated by the flow rate and the inner diameter of the adjustment pipe 125-1. As an example, the target pH value of the drug at the corresponding time point in the device can be set according to the time and pH change of the drug in the body. The value can be calculated to add the corresponding adjustment substance, and then deliver the corresponding volume or corresponding amount of the adjustment substance. In some embodiments, the flow pump 125-2 may be a gas flow pump or a liquid flow pump. The selection type of the flow pump 125-2 can be selected according to the form of the adjustment substance, for example, the adjustment substance in the pH adjustment substance storage bin. If it is carbon dioxide gas, use a gas flow pump; if the adjustment substance in the pH adjustment substance storage bin is a carbonate solution, use a liquid flow pump. In some embodiments, a pump and a solenoid valve may be provided on the regulating pipe 125-1 to transfer the flow of the regulating fluid. The pump here may include at least any one of a peristaltic pump, a centrifugal pump, a circulating pump, and a jet pump.

In some embodiments, the adjusting part 120 further includes a dissolution medium supplementing unit 126, which communicates with the inside of the adjusting part 120 through a supplementary pipe 126-1, and is used to add the dissolving liquid flowing through the adjusting part 120 to The dissolution medium that dissolves the drug. For the connection mode of the dissolution medium replenishing unit 126 communicating with the inside of the adjusting part 120 through the replenishing pipe 126-1, please refer to the connection mode of the pH adjusting substance storage bin communicating with the inside of the adjusting part 120 through the adjusting pipe 125-1, which is not described in detail here. In some embodiments, the dissolution medium may include, but is not limited to, water, hydrochloric acid solution, acetate buffer or phosphate buffer, or any combination thereof. In some embodiments, the pH value of the dissolution medium can be selected according to the body fluids of different parts of the simulated body. For example, the simulated gastric juice can select a hydrochloric acid solution with a pH of 1.2. For another example, a phosphate buffer with a pH of 6.0 can be selected to simulate intestinal fluid. In some embodiments, the dissolution medium may also include components in human body fluids, for example, any one or more of inorganic salts, enzymes, monosaccharides, amino acids, fatty acids, glycerol, water-soluble vitamins, fat-soluble vitamins, etc. kind.

In some embodiments, a flow pump 126-2 is provided on the supplement pipe 126-1, which is configured to limit the amount and/or flow rate of the dissolution medium added for control. For the flow pump 126-2, please refer to the specific description of the flow pump 125-2, which will not be detailed here.

In some embodiments, the device further includes at least one pH detection unit, which is disposed inside the adjusting part 120 and/or inside the dissolution cup 130, and is configured to detect the pH value of the dissolution liquid. In some embodiments, the pH detection unit 150 may be provided in the adjustment part 120. At this time, the pH detection unit 150 is used to detect and monitor the pH value of the eluate in the adjustment part 120, according to the actual pH value detected and the corresponding time period. The target pH value of the adjustment unit 125 (pH buffer storage bin) is transferred to the adjustment unit 120 through the adjustment pipe 125-1 and the flow pump 125-2 to adjust the pH value of the eluate in the adjustment unit 120 Adjust to the target pH value. In some embodiments, the pH detection unit 140 can be provided in the dissolution cup 130. At this time, the pH detection unit 140 can be used to detect the pH value of the dissolution liquid in the dissolution cup 130, and based on the actual pH value detected and the corresponding time period. The target pH value, the adjustment substance in the adjustment unit 125 (pH buffer storage bin) is delivered to the adjustment part 120 through the adjustment pipe 125-1 and the flow pump 125-2 to adjust the pH value of the eluate in the adjustment part 120 Since the regulating part 120 and the dissolution cup 130 are connected through the second pipe 121 and the third pipe 122, the dissolving liquid in the regulating part 120 and the dissolution cup 130 can form a dynamic circulation system. The pH value of can indirectly adjust the pH value of the dissolution liquid in the dissolution vessel 130. In some embodiments, the adjustment part 120 and the dissolution cup 130 may be provided with corresponding pH detection units respectively, so as to keep the pH value of the dissolution liquid in the adjustment part 120 and the dissolution cup 130 consistent. The specific adjustment process can refer to the pH detection unit Set in the adjustment part 120 or the dissolution cup 130 as described in the description. In some embodiments, the pH detection unit may be provided on the second pipe 121 or/and the third pipe 122. In some embodiments, the pH detection unit may not be provided in the adjustment part 120 or the dissolution cup 130. When the adjustment part 120 or/and the dissolution cup 130 needs to be detected, the pH detection unit is placed in the adjustment part 120. Or/and the dissolution cup 130, the specific adjustment process can refer to the description of the pH detection unit provided in the adjustment part 120 or the dissolution cup 130.

In some embodiments, the device may further include a control device that communicates with a pump in the device through an electrical connection and/or a wireless connection, and is configured to control the pump to adjust the amount and/or flow rate of the solution passing through the pump. In some embodiments, the control device may include a switch controller, a pressure controller, a flow controller, etc., or a combination thereof. In some embodiments, the electrical connection may include electrical direct connection, electrical indirect connection, electrical inductive connection, electrical coupling connection, etc., or any combination thereof. Wireless connections include local area network (LAN), wide area network (WAN), Bluetooth, wireless personal area network, and near field communication (NFC), etc., or any combination thereof.

In some embodiments, the device may further include a constant temperature unit (not shown in FIG. 1) for preheating and/or maintaining the absorption part 110 and/or the adjustment part 120. Since the regulating part 120 and the dissolution cup 130 are connected through the second pipe 121 and the third pipe 122, heating the dissolving liquid at the regulating part 120 is equivalent to heating or keeping the temperature of the dissolving liquid inside the entire device to imitate the body The temperature of the internal digestive juice, for example, 37.5°C. The heating method of the absorbing part 110 and/or the adjusting part 120 by the thermostatic unit may include, but is not limited to, electromagnetic heating, infrared heating, resistance heating, etc., or any combination thereof.

The method of drug dissolution can include rotating basket method, paddle method, small cup method, flow cell method, reciprocating cylinder method, cylinder method, paddle dish method, reciprocating rack method, etc. Different measurement methods can be selected according to the type of preparation , And different measuring methods correspond to different measuring equipment. In the embodiment provided in the present application, the drug can be dissolved in the dissolution cup 130, and this process is used to simulate the process of dissolving the drug in the body. The specific dissolution method can be determined according to the specific measurement equipment. For example, when the basket method is adopted, the drug is placed in the basket, and the basket is rotated in the dissolution cup containing the dissolution liquid to realize the dissolution of the drug. For another example, when the paddle method is used, the drug is placed at the bottom of the dissolution cup containing the dissolution liquid, and the drug is dissolved through the stirring of the paddle. When the drug is dissolved, the dissolution liquid containing the drug in the dissolution cup 130 is transported to the regulating part 120 through the second pipe 121 and the second liquid inlet pump 123. The dissolution medium in the regulating part 120 is used to imitate the environment of different parts of the body ( For example, pH). This process is used to simulate the environment of the drug at different parts of the body. The environment of different parts of the body is different, and the solubility of the drug will also change. In this process, the pH adjusting substance storage bin is used to adjust the adjustment part. 120 locations. After the drug-containing dissolving liquid is processed in the regulating part 120, it is transported into the dissolution cup 130 through the third pipe 122 and the first liquid pump 124, and the drug-containing dissolving liquid passes through the first pipe 112 and the first liquid inlet at the same time. The pump 113 is transported to the absorption part 110. The eluent containing the drug delivered to the absorption part 110 represents the part absorbed by the body. During this process, the amount of body fluid inside the body is dynamically balanced, so The dissolution liquid transported to the absorption part 110 needs to be supplemented by the dissolution medium replenishing unit 126 or the adjustment unit 125, so that the dissolution liquid of the entire device is kept within a certain range. In some embodiments, the volume of the dissolution liquid in the dissolution cup 130 can be controlled, specifically by adjusting the flow rates of the second liquid inlet pump 123 and the first liquid outlet pump 124. For example, when the flow rates of the second liquid inlet pump 123 and the first liquid outlet pump 124 are the same, the amount of dissolution liquid in the dissolution cup will be kept within a certain range. For another example, in order to reduce the amount of the dissolution liquid in the dissolution cup 130, while keeping the flow rate of the second liquid inlet pump 123 unchanged, this can be achieved by reducing the flow rate of the first liquid outlet pump 124. For another example, in order to increase the amount of dissolution liquid in the dissolution cup 130, while keeping the flow rate of the second liquid inlet pump 123 constant, this can be achieved by increasing the flow rate of the first liquid outlet pump 124.

It should be noted that the above description is only for convenience of description, and is not used to limit the application. It can be understood that for those skilled in the art, after understanding the principle of the present application, various modifications and changes in form and detail can be made to the above-mentioned auxiliary device without violating this principle. For example, in some embodiments, the pH adjusting substance storage bin may be disposed above the adjusting part 120 or inside the adjusting part 120. In some embodiments, the adjustment unit 125 may also be provided with more storage bins for pH adjustment substances, and the adjustment substances in the storage bins for the pH adjustment substances may be the same or different.

Fig. 2 is a schematic structural diagram of a dissolution test auxiliary device that uses membrane filtration to simulate absorption according to some embodiments of the present application. As shown in Figure 2, the device further includes a fourth pipe 114, which communicates with the absorption unit 111-2 and the dissolution cup 130. After at least part of the eluent flowing into the absorption unit 111-2 flows out, it passes through the fourth pipe 114. Into the dissolution cup 130. In this embodiment, the structure of the absorption unit 111-2 is different from that of the absorption unit 111-1 in the embodiment corresponding to FIG. 1.

In some embodiments, the absorption unit 111-2 includes a membrane filter configured to collect the dissolved medicine and/or part of the dissolving liquid in the dissolving liquid flowing in from the first pipe 112. In some embodiments, the membrane filter may include an ultrafiltration device. In the ultrafiltration process, the drug-containing dissolution liquid flows through the ultrafiltration membrane surface of the membrane filter under pressure, and the solvent (water) and small molecular solutes in the dissolution liquid that are smaller than the membrane pores permeate the ultrafiltration membrane and become the filtrate. , The filtrate flows into the collector 216 through the pipe 214. The undissolved particles larger than the membrane pores in the dissolution liquid are retained, and flow back into the dissolution cup through the fourth pipe 114.

In some embodiments, the membrane material of the membrane filter may include, but is not limited to, cellulose and its derivatives, polycarbonate, polyvinyl chloride, polyvinylidene fluoride, polysulfone, polyacrylonitrile, polyamide, polysulfone amide , Sulfonated polysulfone, cross-linked polyvinyl alcohol, modified acrylic polymer. The membrane material and pore size of the filter membrane can be selected according to the type of drug and the molecular weight of the drug.

In some embodiments, the membrane filter communicates with the eluent supply tank 215 through the eluent inlet pipe 213. The eluent inlet pipe 213 is provided with an eluent inlet pump 211, and the eluent inlet pump 211 is used to transport the eluent in the eluent supply bin 215 to the membrane filter. The inlet speed of the pump 211 and the outlet speed of the outlet pump 212 can adjust the efficiency of ultrafiltration.

In some embodiments, the membrane filter communicates with the eluent recovery bin 216 through the eluent outlet pipe 214. The eluent inlet pipe 214 is provided with an eluent outlet pump 212, and the eluent outlet pump 212 is used to transport the eluent containing the drug to the eluent recovery bin 216 and enter the eluent recovery bin The drugs in 216 simulate the drugs absorbed by the human body.

For the fourth pipe 114, the eluent inlet pipe 213, and the eluent outlet pipe 214, please refer to the specific description of the first pipe 112. For the eluent inlet pump 211 and the eluent outlet pump 212, please refer to the specific description of the first inlet pump 113.

It should be noted that the above description is only for convenience of description, and is not used to limit the application. It can be understood that for those skilled in the art, after understanding the principle of the present application, various modifications and changes in form and detail can be made to the above-mentioned auxiliary device without violating this principle. For example, in some embodiments, the specific number of the eluent supply bin 215 and the eluent recovery bin 216 is not limited to the one shown in FIG. 2, and a plurality of eluent supply bins 215 and Eluent recovery bin 216. In some embodiments, the multiple eluent supply bins 215 may respectively contain different eluents.

Fig. 3 is a schematic structural diagram of a dissolution test auxiliary device that uses an extraction method to simulate absorption according to some embodiments of the present application. The auxiliary device provided in this embodiment of the application has substantially the same structure as the auxiliary device provided in the embodiment shown in FIG. 2, and the biggest difference lies in the different absorption methods. As shown in FIG. 3, the absorption unit 111-3 includes a liquid-liquid extractor, which is configured to collect the medicine dissolved in the dissolution liquid flowing in from the first pipe 112, and the dissolution cup 130 passes through the first pipe 112 and the liquid-liquid extractor. The inside of the extractor is connected. The liquid-liquid extractor is in communication with the dissolution cup 130 through a fourth pipe 114. A second liquid-out pump 115 is provided on the fourth pipe 114. The second liquid-liquid pump 115 is configured to pass the drug-extracted liquid through the fourth pipe 114. Lead back to the dissolution cup 130. The liquid-liquid extractor is a container used to hold the organic solvent. The material of the liquid-liquid extractor can include, but is not limited to, amorphous inorganic non-metallic materials (glass), polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), acrylonitrile- Butadiene-styrene copolymer (ABS), polyethylene terephthalate (PET) or polybutylene terephthalate (PBT). The organic solvent in the liquid-liquid extractor may include, but is not limited to, benzene, toluene, chloroform, carbon tetrachloride, hexane, cyclohexane, ether, ketone, ester, sulfide, sulfoxide, crown ether.

In some embodiments, a stirring device may also be provided in the liquid-liquid extractor. The stirring device may include an anchor stirrer, a paddle stirrer, a propeller stirrer, a turbine stirrer, a ribbon stirrer, etc. or any combination thereof. The drug-containing dissolving liquid in the dissolution cup 130 flows into the liquid-liquid extractor through the first pipe 112, and the stirring device stirs the organic phase solvent and the drug-containing dissolving liquid in the liquid-liquid extractor to realize the drug molecules and the organic phase solvent. Mix well to improve extraction efficiency. . In some embodiments, the organic phase solvent may be located in the upper layer or the lower layer. For example, when dichloromethane, chloroform, carbon tetrachloride, or dichloroethane are used as the organic phase solvent, the organic phase solvent is located in the lower layer.

In some embodiments, the liquid-liquid extractor is in communication with the extraction liquid supply tank 315 through the extraction liquid inlet pipe 313, and an extraction liquid inlet pump 311 is provided on the extraction liquid inlet pipe 313. The extraction liquid inlet pump 311 can be used for The organic phase solvent is supplied to the liquid-liquid extractor. The liquid-liquid extractor is in communication with the extraction liquid receiving chamber 316 through the extraction liquid outlet pipe 314, and the extraction liquid outlet pipe 314 is provided with an extraction liquid outlet pump 312. The extraction liquid outlet pump 312 can be used to remove the organic phase containing the drug It is transported to the extraction liquid recovery bin 316 for collection.

In some embodiments, the extraction liquid inlet pump 311 and/or the extraction liquid outlet pump 312 can move up and down relative to the liquid-liquid extractor through a lifting device. In some embodiments, the lifting device may include, but is not limited to, a lifting rod, a lifting column, and a lifting platform. The lifting device can be realized by means of air cylinders, hydraulic cylinders, gears, transmission chains, conveyor belts, screw rods, etc. For example, by fixing the extraction liquid inlet pump 311 and/or the extraction liquid outlet pump 312 by the air cylinder or hydraulic cylinder, and adjust the extraction liquid inlet pump 311 and/or the extraction liquid by adjusting the movement stroke of the piston rod of the air cylinder or hydraulic cylinder The height of the outlet pump 312. For another example, the screw rod is fixed to the extraction liquid inlet pump 311 and/or the extraction liquid outlet pump 312, and the height of the extraction liquid inlet pump 311 and/or the extraction liquid outlet pump 312 is adjusted by rotating the screw nut. For another example, the height of the extraction liquid inlet pump 311 and/or the extraction liquid outlet pump 312 can be adjusted by the cooperation between the transmission chain or the conveyor belt and the pulley, and by changing the length of the transmission chain or the conveyor belt.

In some embodiments, when the density of the organic phase solvent is lower than that of water (for example, ethyl acetate), the organic phase solvent is located in the upper layer and the aqueous phase solvent is located in the lower layer. For example, the dissolution liquid containing the drug in the dissolution cup 130 enters the liquid-liquid extractor. Due to the gradual addition of the dissolution liquid, the boundary line between the organic phase and the water phase will move up. At this time, the extraction liquid pump 312 can be adjusted. Height so that the extraction liquid inlet pipeline 313 and/or the extraction liquid outlet pipeline 314 are located above the boundary between the organic phase solvent and the aqueous phase, and the extraction liquid outlet pump 312 and the extraction liquid outlet pipeline 314 will be located in the upper layer and contain the drug The organic phase is transported to the extraction liquid recovery bin 316 for collection. In some embodiments, when the density of the organic phase solvent is greater than that of water (for example, carbon tetrachloride), the organic phase solvent is located in the lower layer and the aqueous phase solvent is located in the upper layer. For example, if the drug-containing liquid in the dissolution cup 130 enters the liquid-liquid extractor, the height of the port of the extraction liquid pump 312 can be adjusted so that the port of the extraction liquid pipe 314 is located at the bottom of the liquid-liquid extractor, and the extraction The liquid outlet pump 312 and the extraction liquid outlet pipe 314 transport the organic phase in the lower layer and containing the medicine to the extraction liquid recovery bin 316 for collection. The amount of organic solvent added in the liquid-liquid extractor will affect the efficiency of drug extraction. For example, when the amount of the organic solvent added is larger, the extraction efficiency of the drug is correspondingly higher. For another example, when the amount of the organic solvent added is small, the extraction efficiency of the drug is relatively low. The amount of organic phase added in the liquid-liquid extractor will affect the two-phase boundary line of the organic phase solvent and the aqueous phase solvent. For example, when the density of the organic phase solvent is less than water, the smaller the volume of the dissolved liquid flowing into the liquid-liquid extractor, the lower the two-phase boundary line between the organic phase and the aqueous phase. When the organic phase containing the drug needs to be collected It is possible to adjust the height of the extraction liquid discharge pump 312 so that the extraction liquid discharge pump 312 is located above the two-phase boundary line. For another example, when the density of the organic phase solvent is greater than that of water, the height of the extraction liquid discharge pump 312 can be adjusted so that the extraction liquid discharge pump 312 is located at the bottom of the liquid-liquid extractor.

Please refer to the specific description of the first pipe 112 for the above-mentioned extraction liquid inlet pipe 313 and the extraction liquid outlet pipe 314. For the extraction liquid inlet pump 311 and the extraction liquid outlet pump 312, please refer to the specific description of the first liquid inlet pump 113.

It should be noted that the above description is only for convenience of description, and is not used to limit the application. It can be understood that for those skilled in the art, after understanding the principle of the present application, various modifications and changes in form and detail can be made to the above-mentioned auxiliary device without violating this principle. For example, in some embodiments, the specific number of the extraction liquid supply bin 315 and the extraction liquid recovery bin 316 is not limited to the one shown in FIG. Warehouse 316. In some embodiments, the multiple extraction liquid supply bins 315 may be respectively filled with different organic solvents.

Fig. 4 is another structural schematic diagram of the dissolution test auxiliary device according to some embodiments of the present application. As shown in FIG. 4, the dissolution test auxiliary device may include an absorption part 410 and an adjustment part 420. In some embodiments, the absorbing part 410 and the regulating part 420 are in one container, and a partition is provided inside the container to separate the absorbing part 410 and the regulating part 420. In some embodiments, the absorption part 410 and the adjustment part 420 may be two independent parts. Wherein, the absorption part 410 includes a diverter valve 414 and an absorption unit 413, and the adjustment part 420 includes an adjustment unit 422, which is configured to adjust the pH of the eluent flowing into the adjustment part. The absorption part 410 communicates with the dissolution cup 430 of the drug dissolution device through the first pipe 411, and the absorption part 410 communicates with the adjustment part 420 through the second pipe 421. The first pipe 411 is provided with a liquid inlet pump 412, and the liquid inlet pump 412 is used to transport the dissolved liquid in the dissolution cup 430 through the first pipe 411. The shunt valve 414 is placed on the first pipe 411. The first shunt pipe 415 and the second pipe 421 are respectively connected to the shunt valve 414. The shunt valve 414 shunts the eluent from the dissolution cup 430 through the inlet pump 412. The dissolved liquid flows into the absorption unit 413 through the first branch pipe 415, and another part of the dissolved liquid flows into the regulating part 420 through the second pipe 421.

In some embodiments, the absorption unit 413 includes a liquid collector that communicates with the first pipe 411 through the first branch pipe 415, and the liquid collector can collect a part of the eluate that is branched from the branch valve 414. The liquid trap is connected to the analysis device, and the analysis device can analyze the eluate collected by the liquid trap.

In some embodiments, the adjusting unit 422 includes at least one pH adjusting substance storage bin, which communicates with the inside of the adjusting part 420 through an adjusting pipe 422-1, and is used to add adjusting substances to the eluent flowing through the adjusting part 420 to adjust the eluent.的pH. In some embodiments, different pH adjusting substance storage bins contain different adjusting substances for adding different adjusting substances to the eluent flowing through the adjusting part in different time periods. In some embodiments, the regulating substance includes at least one of the following: carbon dioxide gas, argon gas, nitrogen gas, helium gas, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer, Tris buffer, barbital buffer, phthalate buffer, ammonia-vaporized ammonium buffer, and boric acid buffer.

In some embodiments, the regulating pipe 422-1 is provided with a flow pump 422-2 configured to limit the amount and/or flow rate of the regulating substance added. In some embodiments, the adjusting part 420 further includes a dissolution medium replenishing unit 423, and the dissolution medium replenishing unit 423 is in communication with the inside of the adjusting part 420 through the replenishing pipe 423-1, and is used to add the dissolving liquid flowing through the adjusting part 420 for The dissolution medium that dissolves the drug. In some embodiments, the supplementary pipeline 423-1 is provided with a flow pump 423-2, which is configured to limit the amount and/or flow rate of the added dissolution medium for control.

In some embodiments, the device further includes at least one pH detection unit disposed inside the adjustment part 420 and/or inside the dissolution cup 430, for example, the pH detection unit 450 disposed at the adjustment part 420 is disposed in the dissolution cup 430 The pH detection unit 440, the pH detection unit is configured to detect the pH value of the dissolution liquid.

In some embodiments, the device further includes a constant temperature unit for preheating and/or keeping the absorbing part 410 and/or the adjusting part 420 warm. The constant temperature unit is used to preheat and/or keep the absorption part 410, the adjustment part 420 and/or the dissolution cup 430 warm. Regarding the absorption part 410, the adjustment part 420, the units in each component, the material of the pump, the pipe, the connection method between each pipe and the component, etc. in this embodiment, you can refer to the embodiment shown in FIG. 1, here Do not elaborate.

In the embodiment provided in this application, the medicine can be dissolved in the dissolution cup 430, and this process is used to simulate the process of dissolving the medicine inside the body. After the drug is dissolved, the dissolution liquid containing the drug in the dissolution cup 430 is transported to the absorption part 410 and the adjustment part 420 through the first pipe 411, the inlet pump 412 and the shunt valve 414, respectively. The dissolution medium in the adjustment part 420 is used to simulate The environment of different parts of the body (such as pH). This process is used to simulate the environment of the drug at different parts of the body. The environment of different parts of the body is different, and the solubility of the drug will also change. In this process, the pH adjusting substance is stored The bin is used to adjust the environment at the adjusting part 420. After the drug-containing eluate is processed in the regulating part 420, it is transported into the dissolution cup 430 through the third pipe 431 and the liquid pump 424. At this time, the drug-containing eluate is transported to the absorption part through the first branch pipe 415. In 410, the drug-containing eluate that is delivered to the absorption part 410 represents the part absorbed by the body. During this process, the amount of body fluid inside the body is dynamically balanced, so it is delivered to the absorption part 410. The dissolution liquid needs to be supplemented by the dissolution medium replenishment unit 423 or the adjustment unit 422, so that the dissolution liquid of the entire device is kept within a certain range. In some embodiments, the volume of the dissolution liquid in the dissolution cup 430 can be controlled, specifically by adjusting the flow rates of the liquid inlet pump 412 and the liquid outlet pump 424. For example, when the flow rates of the inlet pump 412 and the outlet pump 424 are the same, the amount of dissolution liquid in the dissolution cup 430 will be kept within a certain range. For another example, in order to reduce the amount of the dissolution liquid in the dissolution cup 430, while keeping the flow rate of the liquid inlet pump 412 constant, this can be achieved by reducing the flow rate of the liquid outlet pump 424. For another example, in order to increase the amount of dissolution liquid in the dissolution cup 430, while keeping the flow rate of the liquid inlet pump 412 constant, this can be achieved by increasing the flow rate of the liquid outlet pump 424.

It should be noted that the above description is only for convenience of description, and is not used to limit the application. It can be understood that for those skilled in the art, after understanding the principle of the present application, various modifications and changes in form and detail can be made to the above-mentioned auxiliary device without violating this principle. For example, in some embodiments, the absorbing part 410 and the adjusting part 420 may be two independent parts. For another example, the pH adjusting substance storage bin may be provided outside the adjusting part 420. For another example, in some embodiments, the adjustment unit 422 may also be provided with more storage bins for pH adjustment substances, and the adjustment substances in the storage bins for the pH adjustment substances may be the same or different.

Based on the embodiment shown in FIG. 4, another embodiment provided by the present application is substantially the same. The biggest difference lies in the difference in the absorption unit. In this embodiment, the device further includes a fourth pipe. The absorption unit and the dissolution cup are connected, and after at least part of the dissolution liquid flowing into the absorption unit flows out, it flows back into the dissolution cup 430 through the fourth pipe. In this embodiment, the absorption unit includes a membrane filter configured to collect the dissolved medicine and/or part of the dissolving liquid flowing into the dissolving liquid from the first shunt pipe 415. The membrane filter is in communication with the eluent supply bin through the eluent inlet pipe. The eluent inlet pipe is equipped with an eluent inlet pump. The eluent inlet pump is used to transport the eluent in the eluent supply bin to the membrane filter. The eluent can be used for the membrane filter. The eluted drug is eluted. The membrane filter is connected with the eluent recovery bin through the eluent outlet pipe. The eluent inlet pipe is equipped with an eluent outlet pump. The eluent outlet pump is used to transport the eluent containing the drug to the eluent recovery bin, and the drug that enters the eluent recovery bin is that Simulates medicines absorbed by the human body. For the specific content in this embodiment, refer to the description in FIG. 2 and the corresponding embodiment.

Based on the above-mentioned embodiment, another embodiment provided by the present application is substantially the same, and the biggest difference lies in the difference in absorption mode. In this embodiment, the absorption unit includes a liquid-liquid extractor, which is configured to collect the drug dissolved in the dissolving liquid flowing in from the first pipe, and the dissolution cup passes through the first pipe, the shunt valve, and the first shunt pipe. The liquid-liquid extractor is connected internally. The liquid-liquid extractor is in communication with the dissolution cup through a fourth pipe, and a second liquid-out pump is arranged on the fourth pipe, and the second liquid-out pump is configured to lead the dissolution liquid after the drug extraction is completed back to the dissolution cup through the fourth pipe. In some embodiments, the liquid-liquid extractor is in communication with the extraction liquid supply tank through an extraction liquid inlet pipe, and an extraction liquid inlet pump is provided on the extraction liquid inlet pipe. The extraction liquid inlet pump can be used to feed the liquid-liquid extractor. Provides organic solvents. The liquid-liquid extractor is connected to the extraction liquid supply tank through the extraction liquid outlet pipe, and the extraction liquid outlet pipe is provided with an extraction liquid outlet pump, which can be used to transport the organic phase containing the drug to the extraction liquid recovery Collect in the warehouse. For the specific content in this embodiment, refer to the description in FIG. 3 and the corresponding embodiment.

The basic concepts have been described above. Obviously, for those skilled in the art, the above detailed disclosure is only an example, and does not constitute a limitation to the application. Although it is not explicitly stated here, those skilled in the art may make various modifications, improvements and amendments to this application. Such modifications, improvements, and corrections are suggested in this application, so such modifications, improvements, and corrections still belong to the spirit and scope of the exemplary embodiments of this application.

At the same time, this application uses specific words to describe the embodiments of the application. For example, "one embodiment", "an embodiment", and/or "some embodiments" mean a certain feature, structure, or characteristic related to at least one embodiment of the present application. Therefore, it should be emphasized and noted that “one embodiment” or “one embodiment” or “an alternative embodiment” mentioned twice or more in different positions in this specification does not necessarily refer to the same embodiment. . In addition, some features, structures, or characteristics in one or more embodiments of the present application can be appropriately combined.

For the same reason, it should be noted that, in order to simplify the expressions disclosed in this application and help the understanding of one or more embodiments of the invention, in the foregoing description of the embodiments of this application, multiple features are sometimes combined into one embodiment. In the drawings or its description. However, this method of disclosure does not mean that the subject of the application requires more features than those mentioned in the claims. In fact, the features of the embodiment are less than all the features of the single embodiment disclosed above.

For each patent, patent application, patent application publication and other materials cited in this application, such as articles, books, specifications, publications, documents, etc., the entire contents of which are hereby incorporated into this application by reference. The application history documents that are inconsistent or conflicting with the content of this application are excluded, and documents that restrict the broadest scope of the claims of this application (currently or later attached to this application) are also excluded. It should be noted that if there is any inconsistency or conflict between the description, definition, and/or term usage in the attached materials of this application and the content described in this application, the description, definition and/or term usage of this application shall prevail .

Finally, it should be understood that the embodiments described in this application are only used to illustrate the principles of the embodiments of this application. Other variations may also fall within the scope of this application. Therefore, as an example and not a limitation, the alternative configuration of the embodiment of the present application can be regarded as consistent with the teaching of the present application. Correspondingly, the embodiments of the present application are not limited to the embodiments explicitly introduced and described in the present application.

Claims

A dissolution test auxiliary device, characterized in that the device comprises: an absorption part and an adjustment part, wherein the absorption part includes an absorption unit, and the adjustment part includes an adjustment unit;

The absorbing part communicates with the dissolution cup of the drug dissolution device through the first pipe;

The adjustment part is in communication with the dissolution cup through a second pipe and a third pipe;

The first pipeline, the second pipeline and the third pipeline are respectively provided with a first inlet pump, a second inlet pump and a first outlet pump;

Wherein, the first liquid inlet pump is configured to introduce the eluate in the dissolution cup into the absorption part through the first pipe, and the introduced eluate flows into the absorption unit;

The second feed pump is configured to introduce the eluate in the dissolution cup into the adjusting part through the second pipe, and the adjusting unit is configured to adjust the pH and/or volume of the introduced eluate , The first liquid discharge pump is configured to lead the adjusted dissolution liquid back to the dissolution cup.
The device according to claim 1, wherein the absorption unit comprises a liquid trap, and the liquid trap is capable of collecting the eluent flowing in from the first pipe.
The apparatus according to claim 2, wherein the liquid trap is connected to an analysis device, and the analysis device is capable of analyzing the eluate collected by the liquid trap.
The device according to claim 1, wherein the device further comprises a fourth pipe, the fourth pipe is connected to the absorption unit and the dissolution cup, after at least part of the dissolution liquid flowing into the absorption unit flows out , Flowing back into the dissolution cup through the fourth pipe.
The device according to claim 4, wherein the absorption unit comprises a membrane filter configured to collect the dissolved medicine and/or part of the dissolving liquid in the dissolving liquid flowing in from the first pipe.
The device according to claim 4, wherein the absorption unit comprises a liquid-liquid extractor configured to collect the medicine dissolved in the eluent flowing in from the first pipe;

The fourth pipeline is provided with a second liquid outlet pump, and the second liquid outlet pump is configured to guide the eluent from which the medicine has been extracted back to the dissolution cup through the fourth pipeline.
The device according to any one of claims 1-6, wherein the adjusting unit comprises at least one pH adjusting substance storage bin, which is communicated with the inside of the adjusting part through an adjusting pipe for flowing through the An adjustment substance is added to the eluate of the adjusting part to adjust the pH of the eluate.
The device according to any one of claims 1-7, wherein different pH adjusting substance storage bins contain different adjusting substances, which are used to transfer the eluent flowing through the adjusting part in different time periods. Add different regulating substances.
The device according to any one of claims 7 or 8, characterized in that the adjusting substance includes at least one of the following: carbon dioxide gas, argon gas, nitrogen gas, helium gas, water, carbonate buffer, phosphate buffer Solution, Citrate Buffer, Acetate Buffer, Tris buffer, Barbiturate Buffer, Phthalate Buffer, Ammonia-Ammonia Buffer, and Boric Acid Buffer .
The device according to any one of claims 7-9, wherein a flow pump is provided on the regulating pipe, which is configured to limit the amount and/or flow rate of the added regulating substance.
The device according to any one of claims 1-10, wherein the adjustment part further comprises a dissolution medium replenishment unit, and the dissolution medium replenishment unit communicates with the inside of the adjustment part through a replenishment pipe for A dissolution medium for dissolving the drug is added to the dissolution liquid flowing through the regulating part.
The device according to claim 11, characterized in that a flow pump is provided on the supplementary pipe, which is configured to limit the amount and/or flow rate of the added dissolution medium for control.
The device according to any one of claims 1-12, wherein the device further comprises at least one pH detection unit, which is arranged inside the adjusting part and/or inside the dissolution cup or on the third pipe , Is configured to detect the pH value of the dissolution liquid.
The device according to any one of claims 1-13, wherein the device further comprises a control device, which communicates with the pump in the device through an electrical connection and/or a wireless connection, and is configured to control the pump to Adjust the amount and/or flow rate of the solution passing through the pump.
The device according to any one of claims 1-14, wherein the device further comprises a constant temperature unit for preheating and/or keeping the temperature of the absorption part and/or the adjustment part.
A dissolution test auxiliary device, characterized in that the device comprises: an absorption part and an adjustment part, wherein the absorption part includes a shunt valve and an absorption unit, and the adjustment part includes an adjustment unit;

The absorbing part communicates with the dissolution cup of the drug dissolution device through a first pipe, and communicates with the adjusting part through a second pipe;

The adjusting part is in communication with the dissolution cup through a third pipe;

The first pipe and the third pipe are respectively provided with an inlet pump and an outlet pump;

Wherein, the diverter valve is placed on the first pipe to diverge the eluent from the dissolution cup through the inlet pump, a part of the eluent flows into the absorption unit, and the other part of the eluent flows into the regulating part;

The adjusting unit of the adjusting part is configured to adjust the pH of the eluent flowing into the adjusting part, and the eluent pump is configured to return the pH-adjusted eluent to the dissolution cup.
The device according to claim 16, wherein the absorption unit comprises a liquid trap, and the liquid trap is capable of collecting a part of the eluate that is diverted from the diverter valve.
The apparatus according to claim 17, wherein the liquid trap is connected to an analysis device, and the analysis device is capable of analyzing the eluate collected by the liquid trap.
The device according to any one of claims 16-18, wherein the adjusting unit comprises at least one pH adjusting substance storage bin, which is communicated with the inside of the adjusting part through an adjusting pipe for flowing through the An adjustment substance is added to the eluate of the adjusting part to adjust the pH of the eluate.
The device according to any one of claims 16-19, wherein the different pH adjusting substance storage bins contain different adjusting substances, which are used to dissolve the eluent flowing through the adjusting part in different time periods. Add different regulating substances
The device according to any one of claims 19 or 20, wherein the adjusting substance comprises at least one of the following: carbon dioxide gas, argon gas, nitrogen gas, helium gas, water, carbonate buffer, phosphate buffer Solution, Citrate Buffer, Acetate Buffer, Tris buffer, Barbiturate Buffer, Phthalate Buffer, Ammonia-Ammonia Buffer, and Boric Acid Buffer .
The device according to any one of claims 19-21, wherein a flow pump is provided on the regulating pipe, which is configured to limit the amount and/or flow rate of the regulating substance added.
The device according to any one of claims 16-22, wherein the adjustment part further comprises a dissolution medium replenishment unit, the dissolution medium replenishment unit communicates with the interior of the adjustment part through a replenishment pipe for A dissolution medium is added to the dissolution liquid flowing through the regulating part.
The device according to claim 23, characterized in that a flow pump is provided on the supplementary pipe, which is configured to limit the amount and/or flow rate of the added dissolution medium for control.
The device according to any one of claims 16-24, wherein the device further comprises at least one pH detection unit, which is arranged inside the adjusting part and/or inside the dissolution cup, and is configured to detect The pH value of the dissolution liquid.
The device according to any one of claims 16-25, wherein the device further comprises a control device, which communicates with the pump in the device through an electrical connection and/or a wireless connection, and is configured to control the pump to Adjust the amount and/or flow rate of the solution passing through the pump.
The device according to any one of claims 16-26, wherein the device further comprises a constant temperature unit for preheating and/or keeping the temperature of the absorption part and/or the adjustment part;

It is used to preheat and/or keep the absorption chamber, the adjustment part and/or the dissolution cup.