阅读说明：本技术 一种药物体外质量评价可视化装置及方法 (Visualization device and method for evaluating in-vitro quality of medicine ) 是由 邓黎 符垚 杨怡晨 于 2021-10-25 设计创作，主要内容包括：本发明公开一种药物体外质量评价可视化装置,包括恒温组件和至少一个混合液容器,所述恒温组件内部设有溶出组件,所述混合液容器分别通过两条连接管道与溶出组件内部连通,其中一条所述连接管道上设有第一输送泵,另一条所述连接管道上通过测量管道连接有实时测定装置,所述恒温组件上方和侧方均设有影像采集装置,所述恒温组件外侧与溶出组件对应的位置设有至少一个可调节光源。本发明兼具溶出测定和现象记录的功能,可使体外评价发挥最大作用,为药物研发和体内实验提供最大保障。(The invention discloses a visualization device for external quality evaluation of a medicine, which comprises a constant temperature component and at least one mixed liquid container, wherein a dissolving-out component is arranged in the constant temperature component, the mixed liquid container is respectively communicated with the inside of the dissolving-out component through two connecting pipelines, one connecting pipeline is provided with a first delivery pump, the other connecting pipeline is connected with a real-time measuring device through a measuring pipeline, image acquisition devices are arranged above and on the side of the constant temperature component, and at least one adjustable light source is arranged at the position, corresponding to the dissolving-out component, on the outer side of the constant temperature component. The invention has the functions of dissolution measurement and phenomenon recording, can make in vitro evaluation play the greatest role, and provides the greatest guarantee for drug research and development and in vivo experiments.)

1. The utility model provides a visual device of external quality evaluation of medicine, its characterized in that, mixes liquid container (2) including constant temperature subassembly (1) and at least one, the inside subassembly (4) of dissolving out that is equipped with of constant temperature subassembly (1), mix liquid container (2) respectively through two connecting tube (5) and the inside intercommunication of dissolving out subassembly (4), one of them be equipped with first delivery pump (6) on connecting tube (5), another be connected with real-time assay device (8) through measuring pipeline (3) on connecting tube (5), constant temperature subassembly (1) top and side all are equipped with image acquisition device (9), the position that corresponds with dissolving out subassembly (4) in the constant temperature subassembly (1) outside is equipped with at least one adjustable light source (10).

2. The device for visualizing the in vitro quality evaluation of drugs as claimed in claim 1, wherein there is one mixed liquor container (2).

3. The visualization device for in-vitro quality evaluation of drugs according to claim 1, wherein the number of the mixed solution containers (2) is two, one mixed solution container (2) is a medium container (21), and the other mixed solution container (2) is a dissolution solution container (22).

4. The device for visualizing the in vitro quality evaluation of a drug as claimed in claim 3, wherein one of said connecting conduits (5) communicates between the medium container (21) and the dissolution assembly (4), the other connecting conduit (5) communicates between the dissolution liquid container (22) and the dissolution assembly (4), and said first delivery pump (6) is arranged on the connecting conduit (5) communicating between the medium container (21) and the dissolution assembly (4).

5. The device for visualizing the in vitro quality evaluation of a drug as claimed in claim 4, wherein a second delivery pump (7) is arranged on the connecting pipeline (5) communicating the dissolution fluid container (22) and the dissolution assembly (4), and the real-time determination device (8) is communicated with the second delivery pump (7) through the measurement pipeline (3).

6. A visualization device for external quality evaluation of drugs according to claim 2 or 5, characterized in that the connection tube (5) provided with the first delivery pump (6) is in communication with the inner bottom surface of the dissolution module (4).

7. The visualization device for in-vitro quality evaluation of drugs according to claim 6, wherein the dissolution component (4) is a dissolution cup which is a hexahedral quartz cup, and the length, width and height of the quartz cup are all 5-100 mm.

8. The device for visualizing the in vitro quality of a drug according to claim 7, wherein the image acquisition devices (9) disposed above and laterally to the thermostatic element (1) are each at least one and are each disposed at a position corresponding to the dissolution element (4).

9. The device for visualizing in vitro quality assessment of drugs as claimed in claim 8, wherein said image acquisition device (9) comprises at least one of an optical imager, an ultraviolet imager or an infrared imager.

10. A visualization method for in-vitro quality evaluation of a medicament is characterized by comprising the following steps:

step 10, injecting a constant temperature medium into the constant temperature component (1), keeping the constant temperature of the constant temperature medium, and injecting a dissolving medium into the mixed liquid container (2);

step 20, a first delivery pump (6) works to send the dissolution medium in the mixed liquid container (2) into the dissolution assembly (4) through a connecting pipeline (5);

step 30, placing the medicine in the dissolution assembly (4), and adjusting the positions of the image acquisition device (9) and the adjustable light source (10) to enable the image acquisition device (9) and the adjustable light source (10) to align with the medicine;

step 40, gradually disintegrating the medicine under the action of the dissolution medium, and acquiring and storing a disintegration image of the medicine in real time by an image acquisition device (9);

and 50, mixing the disintegrated medicine with a dissolution medium to form a dissolution liquid, enabling the dissolution liquid to enter the mixed liquid container (2) through another connecting pipeline (5), and measuring and recording the dissolution rate of the dissolution liquid in real time by a real-time measuring device (8).

Technical Field

The invention belongs to the field of in-vitro quality evaluation of medicines, and particularly relates to a visualization device and method for in-vitro quality evaluation of medicines.

Background

At present, the evaluation work aiming at the imitation pharmacy consistency of oral solid preparations in China mainly comprises whether the external pharmacy is consistent with the internal medicine effect. The in vitro pharmaceutical consistency is mainly evaluated through an in vitro dissolution test, the in vitro dissolution test data belongs to the common evaluation index of a pharmaceutical preparation, and the in vivo release process of the drug can be reflected to a certain extent, and the pharmacological kinetics and the bioavailability of the drug are reflected, so that the in vivo behavior of the drug can be predicted, a reference is provided for the research and development of the drug, and a basis is provided for the in vivo experiment. The main in vitro dissolution device comprises a basket method, a paddle method, a small cup method, a paddle-dish method, a rotary drum method, a flow cell method, a reciprocating cylinder method and the like, and the dissolution and release conditions of the medicine are observed.

When the existing dissolving device is used for inspecting the dissolution and the release of the medicine, most of the adopted conditions are stirring, the stirring intensity degree cannot accurately simulate the peristalsis of the gastrointestinal tract, the difference between the medicines is easily smoothed in a dissolution test, and the in-vitro evaluation of the medicine is not facilitated. For insoluble drugs, most of the existing dissolution devices add certain surfactants to ensure that the conditions of a leak groove are met, so that more uncontrollable factors such as the dosage of the surfactants and manufacturers are increased, while the flow cell method can better solve the problem, but the domestic application is not wide. Meanwhile, the data acquired by the traditional dissolving device is only the concentration of the drug in the solution, and the phenomenon of the disintegration and dissolution process of the drug is ignored, so that the data of the tablet surface can limit the obtained conclusion and the in vitro evaluation cannot play the maximum role.

Therefore, for the evaluation of the pharmaceutical imitation consistency of the oral solid preparation, a device which can perform dissolution measurement and phenomenon recording at the same time is needed, so that the in vitro evaluation plays the most role, and the maximum guarantee is provided for drug research and development and in vivo experiments.

Disclosure of Invention

The technical problem to be solved by the invention is to provide a visualization device and method for in vitro quality evaluation of a drug, aiming at the defects of the prior art, wherein the visualization device and method have the functions of dissolution measurement and phenomenon recording, can make in vitro evaluation play the greatest role, and provide the greatest guarantee for drug research and development and in vivo experiments.

The technical scheme adopted by the invention is as follows: the utility model provides a visual device of external quality evaluation of medicine, includes constant temperature component and at least one mixed liquid container, the inside subassembly of dissolving out that is equipped with of constant temperature component, mixed liquid container is respectively through two connecting tubes and the inside intercommunication of dissolving out the subassembly, one of them be equipped with first delivery pump on the connecting tube, another be connected with real-time survey device through measuring the pipeline on the connecting tube, constant temperature component top and side all are equipped with image acquisition device, the constant temperature component outside is equipped with at least one adjustable light source with the position that the subassembly corresponds of dissolving out.

In one embodiment, the mixed liquor container is one.

In one embodiment, the number of the mixed liquid containers is two, wherein one mixed liquid container is a medium container, and the other mixed liquid container is a dissolution liquid container.

In one embodiment, one of the connecting pipelines is communicated with the medium container and the digestion assembly, the other connecting pipeline is communicated with the digestion liquid container and the digestion assembly, and the first delivery pump is arranged on the connecting pipeline communicated with the medium container and the digestion assembly.

In one embodiment, a second delivery pump is arranged on a connecting pipeline for communicating the dissolution liquid container and the dissolution assembly, and the real-time determination device is communicated with the second delivery pump through a measurement pipeline.

In one embodiment, the connecting pipe provided with the first conveying pump is communicated with the inner bottom surface of the digestion assembly.

In one embodiment, the dissolution component is a dissolution cup which is a hexahedral quartz cup, and the length, the width and the height of the quartz cup are 5 mm-100 mm.

In one embodiment, the image acquisition devices arranged above and at the side of the constant temperature component are at least one and are arranged at the positions corresponding to the dissolution component.

In one embodiment, the image acquisition device comprises at least one of an optical imager, an ultraviolet imager or an infrared imager.

The invention also discloses a visualization method for evaluating the in vitro quality of the medicine, which comprises the following steps:

step 10, injecting a constant temperature medium into the constant temperature component, keeping the constant temperature medium at a constant temperature, and injecting a dissolving-out medium into the mixed liquid container;

step 20, the first delivery pump works, and the dissolution medium in the mixed liquid container is sent into the dissolution assembly through a connecting pipeline;

step 30, placing the medicine in the dissolution assembly, and adjusting the positions of the image acquisition device and the adjustable light source to enable the image acquisition device and the adjustable light source to align the medicine;

step 40, gradually disintegrating the medicine under the action of the dissolution medium, and collecting and storing a disintegration image of the medicine in real time by an image collecting device;

and 50, mixing the disintegrated medicine with a dissolution medium to form a dissolution liquid, enabling the dissolution liquid to enter a mixed liquid container through another connecting pipeline, and measuring and recording the dissolution rate of the dissolution liquid in real time by a real-time measuring device.

The invention has the beneficial effects that:

1. compared with the traditional dissolving device, the device has no conditions such as violent stirring and the like, and a plurality of uncertain factors are reduced; meanwhile, not only can the concentration data of the medicine be collected, but also the complete disintegration image process of the medicine can be recorded.

2. The device has the advantages that certain differences among the medicines can be reflected in an in-vitro dissolution test, and differences are analyzed visually by combining images; and the difference is reasonable, and more reliable guarantee can be provided for drug research and development and in-vivo drug effect.

Drawings

FIG. 1 is a schematic structural view of example 1 of the present invention;

fig. 2 is a schematic structural diagram of embodiment 2 of the present invention.

In the figure: 1. a constant temperature component; 2. a mixed liquid container; 3. measuring a pipeline; 4. a digestion assembly; 5. connecting a pipeline; 6. a first delivery pump; 7. a second delivery pump; 8. a real-time measuring device; 9. an image acquisition device; 10. an adjustable light source; 21. a media container; 22. a solution container.

Detailed Description

The invention will be described in further detail with reference to the following drawings and specific embodiments.

Example 1:

as shown in fig. 1, a visual device for evaluating external quality of a medicine comprises a constant temperature component 1 and at least one mixed liquid container 2, wherein a dissolution component 4 is arranged inside the constant temperature component 1, the mixed liquid container 2 is communicated with the inside of the dissolution component 4 through two connecting pipelines 5, one of the connecting pipelines 5 is provided with a first delivery pump 6, the other connecting pipeline 5 is connected with a real-time measuring device 8 through a measuring pipeline 3, image acquisition devices 9 are arranged above and on the side of the constant temperature component 1, and at least one adjustable light source 10 is arranged at the position, corresponding to the dissolution component 4, outside the constant temperature component 1. The mixed liquid container 2 is one.

In this embodiment, the liquid (dissolution medium, dissolution liquid, etc.) is circulated in a closed loop, i.e., the dissolution medium and the dissolution liquid are mixed to form a mixed liquid, and the mixed liquid is circulated between the mixed liquid vessel 2 and the dissolution module 4 by the first transfer pump 6. Therefore, in the present embodiment, the mixed liquid container 2 has both the collecting and storing functions.

Example 2:

as shown in fig. 2, a visual device for evaluating external quality of a medicine comprises a constant temperature component 1 and at least one mixed liquid container 2, wherein a dissolution component 4 is arranged inside the constant temperature component 1, the mixed liquid container 2 is communicated with the inside of the dissolution component 4 through two connecting pipelines 5, one of the connecting pipelines 5 is provided with a first delivery pump 6, the other connecting pipeline 5 is connected with a real-time measuring device 8 through a measuring pipeline 3, image collecting devices 9 are arranged above and on the side of the constant temperature component 1, and at least one adjustable light source 10 is arranged at the position, corresponding to the dissolution component 4, outside the constant temperature component 1. The number of the mixed liquid containers 2 is two, wherein one mixed liquid container 2 is a medium container 21, and the other mixed liquid container 2 is a dissolution liquid container 22. One of the connecting pipelines 5 is communicated with the medium container 21 and the digestion assembly 4, the other connecting pipeline 5 is communicated with the digestion liquid container 22 and the digestion assembly 4, and the first delivery pump 6 is arranged on the connecting pipeline 5 communicated with the medium container 21 and the digestion assembly 4. A second delivery pump 7 is arranged on the connecting pipeline 5 for communicating the dissolution liquid container 22 with the dissolution component 4, and the real-time determination device 8 is communicated with the second delivery pump 7 through the measurement pipeline 3.

In this embodiment, the liquid (dissolution medium, dissolution liquid, etc.) is circulated in an open loop manner, that is, the dissolution medium and the dissolution liquid are stored separately and are not mixed. The media vessel 21 is used to store dissolution media. The dissolution liquid container 22 is used for storing dissolution liquid. The first transfer pump 6 and the second transfer pump 7 are used for feeding the dissolution medium in the medium vessel 21 into the dissolution module 4 and for feeding the dissolution liquid in the dissolution module 4 out of the dissolution module 4 and into the dissolution liquid vessel 22, respectively.

In the present apparatus, the dissolution liquid of the dissolution liquid container 22 can be collected by an automatic collection device and a manual collection device. Both devices are classified according to the stability of the test compound. Wherein:

an automatic collecting device: a compound suitable for stabilization in a prescribed medium within an image acquisition time range; compounds that did not require immediate pretreatment for analysis after collection.

Manual collection device: compounds suitable for being unstable in a prescribed medium within an image acquisition time range; compounds that require immediate pretreatment for analysis after collection.

In both embodiments, the connecting pipe 5 provided with the first transfer pump 6 is communicated with the inner bottom surface of the dissolution module 4.

The dissolution medium or the mixed solution is injected into the dissolution component 4 from the bottom, so that the inside of the dissolution component 4 can achieve a better laminar flow condition, and no turbulent flow is generated, thereby ensuring the dissolution effect. Therefore, the connection pipe 5 provided with the first transfer pump 6 is preferably in communication with the inner bottom surface of the digestion unit 4.

In the two embodiments, the digestion assembly 4 is a digestion cup which is a hexahedral quartz cup, and the length, width and height of the quartz cup are 5 mm-100 mm.

Conventional drug dissolution is typically achieved through a dissolution cup or flow cell. The dissolution cup is generally a 1000ml cup-shaped vessel made of hard glass or other inert materials with a hemispherical bottom; the flow cell is a container with an upper half cylinder and a lower half cone made of transparent inert materials. Neither the dissolution cup nor the flow cell can meet the requirement of accurate image acquisition, and the gastrointestinal condition can not be accurately simulated. In this apparatus, the dissolution module 4 is provided as a quartz cup having a rectangular parallelepiped or square shape and a conical or flat bottom.

When the quartz cup is adopted as the dissolution component 4, the liquid amount can be maintained at about 5 ml-250 ml in the process of liquid circulation, the liquid amount can be controlled to be close to the normal basic stomach liquid amount by 10 ml-100 ml, and the leakage groove conditions of different medicines can be met by adjusting the flow rate; meanwhile, the hexahedral quartz cup, particularly the cuboid or square quartz cup, has good light transmittance and pure picture, and can meet the requirement of accurate image acquisition.

In the above two embodiments, the image capturing devices 9 provided above and at the side of the thermostatic element 1 are both at least one and are both provided at positions corresponding to the elution element 4.

Image acquisition device 9 sets up in constant temperature component 1 top and side and be at least one, can adjust according to actual conditions to guarantee to have good image acquisition angle.

In the above two embodiments, the image capturing device 9 includes at least one of an optical imager, an ultraviolet imager, or an infrared imager.

The image acquisition device 9 in the present device includes, but is not limited to, an optical imager, an ultraviolet imager, or an infrared imager. The optical imager is used for imaging in a visible light range; the image of the ultraviolet imager can directly reflect the distribution of the space electric field; the infrared imager may reflect the distribution of the temperature field. Different image capturing devices 9 can meet different purposes, and therefore the image capturing devices 9 can be replaced or combined according to purposes.

The image capturing device 9 disposed at the side needs to complete image data capturing at least two angles. For drugs with regular morphology, the visual observation can be satisfied by acquiring image data at two angles such as circle and square, so that two image acquisition devices 9 are adopted. At this time, the angle of the image capturing device 9 is adjusted to 90 °. For drugs with irregular shapes, more than two angles of image acquisition are needed, and the number and angles of the image acquisition devices 9 are determined according to the actual shape of the tablet.

The thermostatic assembly 1 of the present apparatus is used for keeping the dissolution medium entering the thermostatic assembly 1 warm, and includes, but is not limited to, a water bath apparatus, an air bath apparatus. Before the thermostatic component 1 is used, a thermostatic medium needs to be injected into the thermostatic component 1, and the thermostatic medium is determined according to the type of the thermostatic component 1 used specifically. The dissolution component 4 is used for placing medicines and providing a place for dissolution of the medicines, and is matched with a bracket to be arranged in the constant temperature component 1 when in use. The connecting pipe 5 is used to connect the mixed liquid container 2 and the dissolution module 4, and if there are two mixed liquid containers 2, the medium container 21 and the dissolution module 4 are connected, and the dissolution liquid container 22 and the dissolution module 4 are connected, respectively. The real-time measuring device 8 is used for measuring and recording the dissolved amount of the drug in real time, and includes but is not limited to a fiber optic real-time drug dissolution tester. The image acquisition device 9 is used for capturing and recording the disintegration phenomenon of the medicine in the medium at multiple angles. The adjustable light source 10 is used to provide a stable light source for image acquisition during dissolution.

After the dissolution component 4 produces the dissolution liquid, if the drug has good stability in a specified medium and has the characteristics of ultraviolet absorption and no interference of other components, the real-time measurement can be performed by the real-time measurement device 8 without further processing. Meanwhile, if the aim is to measure the dissolution content of the medicine, the dissolution liquid is not collected independently. The purpose is to measure the content of the drug and measure and identify other compounds, and the eluate needs to be collected for further analysis, such as spectrum and chromatographic analysis, and different detectors are used for meeting the measurement requirement. If the drug is not stable well in a specified medium and does not have ultraviolet absorption, pretreatment is required before measurement; or the elution solution has ultraviolet absorption but other components are seriously interfered, the elution solution needs to be collected, a proper chromatographic instrument is selected according to the property of the compound to be detected to be matched with a detector for measurement, and the collected elution solution needs to be pretreated and then is measured.

The first conveying pump 6 and the second conveying pump 7 of the device are both peristaltic pumps. The peristaltic pump can provide medium flow power and control the flow rate of the medium, and can better control the dissolution process.

The angle of the adjustable light source 10 of the device is required to satisfy the requirements of illuminating the image acquisition picture range and not causing interference to image acquisition. Thus, the adjustable light source 10 has the feature of being nearly 360 adjustable. Aiming at collecting medicines at two angles, only one adjustable light source 10 is needed, and different light supplement small parts are needed to be matched around the dissolution component 4. For drugs collected at more than two angles, the number of adjustable light sources 10 is increased to meet the requirement of image collection. However, the light source used must be stable, adjustable in brightness and adjustable in angle 360 °.

The invention also discloses a visualization method for evaluating the in vitro quality of the medicine, which comprises the following steps:

step 10, injecting a constant temperature medium into the constant temperature component 1, keeping the constant temperature medium at a constant temperature, and injecting a dissolving medium into the mixed liquid container 2;

step 20, the first delivery pump 6 works to deliver the dissolution medium in the mixed liquid container 2 to the dissolution component 4 through the connecting pipeline 5;

step 30, placing the medicine in the dissolution component 4, and adjusting the positions of the image acquisition device 9 and the adjustable light source 10 to enable the image acquisition device 9 and the adjustable light source 10 to be aligned with the medicine;

step 40, gradually disintegrating the medicine under the action of the dissolution medium, and acquiring and storing a disintegration image of the medicine in real time by the image acquisition device 9;

and 50, mixing the disintegrated medicine with a dissolution medium to form a dissolution liquid, enabling the dissolution liquid to enter the mixed liquid container 2 through the other connecting pipeline 5, and measuring and recording the dissolution rate of the dissolution liquid in real time by the real-time measuring device 8.

In the above method, the image acquired by the image acquisition device 9 may be subjected to image AI identification processing, for example:

the diffusion track and speed of the drug particles are tracked to combine with different analysis results. Is suitable for the medicine with quick disintegration and common disintegration medicine release mechanism.

Secondly, morphological information is collected from morphology according to the medicine regular medicine release characteristics and converted into a mathematical model, the model is suitable for skeleton type medicine release and osmotic pump type medicine release mechanisms, and the morphological change of the medicine is closely related to the release of the medicine.

And thirdly, converting certain color in the collected image into a digital form by using color modes such as an RGB mode, a CMYK mode, an HSB mode, a Lab color mode, a bitmap mode, a gray scale mode, an index color mode, a two-tone mode, a multi-channel mode and the like, and extracting information for further analysis. The method is suitable for medicines with color change and transparency change, and can obtain relevant information of certain changes of the medicines and combine the information with other analysis results.

The dissolution rate measured by the real-time measuring device 8 can obtain the change relation of the drug concentration with time, and meanwhile, the accumulated dissolution rate can be obtained according to the specific flow rate. The result can be compared with the traditional dissolution result and combined with the image result to draw conclusions from more angles, thereby providing guarantee for prescription screening and process development.

The above-mentioned embodiments only express the specific embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention.