CN211373993U - Test equipment for improving in-vivo and in-vitro correlation of inhalation preparation - Google Patents
Test equipment for improving in-vivo and in-vitro correlation of inhalation preparation Download PDFInfo
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- CN211373993U CN211373993U CN201921552135.3U CN201921552135U CN211373993U CN 211373993 U CN211373993 U CN 211373993U CN 201921552135 U CN201921552135 U CN 201921552135U CN 211373993 U CN211373993 U CN 211373993U
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Abstract
In order to solve a plurality of defects of the aerodynamic characteristic determination of the micro-particles of the preparation by adopting a cascade impactor, the test device for improving the in-vivo and in-vitro correlation of the inhaled preparation is provided, and comprises: device (1), human respiratory tract model (2) and breathing analog machine (3) of dosing, human respiratory tract model (2) include: the breathing simulator comprises an adapter (21), a real human body respiratory tract 3D solid model (22), a breathing simulator (3) and a breathing data acquisition device (34), wherein the breathing simulator (3) comprises a connection control assembly (31), a piston type locomotory apparatus (32), a control system (33) and a breathing data acquisition device (34), a plurality of first quick connection interfaces (221) are arranged on the real human body respiratory tract 3D solid model (22), the plurality of first quick connection interfaces (221) are finally converged into a total air path through a plurality of air paths and then connected to an inlet end of the connection control assembly (31), and an outlet end of the connection control assembly (32) is connected to the piston type locomotory apparatus (32); the connection control assembly (31) comprises a first electromagnetic valve (311), a second electromagnetic valve (312), a third electromagnetic valve (313), an electronic flow meter (315) and a main body air passage.
Description
Technical Field
The utility model belongs to the technical field of medical instrument, it is comparatively specific, the utility model relates to an improve the internal external correlation equipment of inhalation preparation, this equipment is arranged in the deposit evaluation of inhalation preparation in external human respiratory track and can improves the correlation of external test result and internal test result, improves the accuracy of the external evaluation of inhalation preparation, reduces inhalation preparation development time and internal test cost.
Background
The respiratory system is an important component of the human body, is an important way for the human body to exchange substances with the outside, and is certainly a way for external particles to enter the respiratory tract. Diseases due to the respiratory process are numerous, for example: asthma, Chronic Obstructive Pulmonary Disease (COPD), lung cancer, and the like. According to literature reports, Chronic Obstructive Pulmonary Disease (COPD) ranks the third position of global fatal diseases, and nearly 9990 thousands of chronic obstructive pulmonary disease patients exist in China at present.
Inhalation formulations have become an important research focus and drug development focus as an effective means of targeted and systemic administration to the lungs, especially with natural advantages in the treatment of respiratory diseases. Inhalation formulations include aerosol inhalants, powder inhalants, liquid formulations for nebulizers and formulations convertible to vapor. Currently available inhalation formulations on the market are classified according to function and include various treatments for asthma, insulin, antibiotics, etc.
Clinical trials of inhaled formulations are an indispensable in vivo test method as the most important link in drug validation and approval. However, due to the high cost of clinical trials, it is generally necessary to perform in vitro tests prior to evaluation in the testing process of new drug development or the evaluation of the pharmaceutical-mimetic consistency. Current in vitro testing methods generally use an ideal airway model for the testing of agent deposition, which results in a large gap between in vitro test results and true clinical test results. Aiming at the problem of relevance of in-vitro test of the inhalation preparation, the invention is innovatively designed from two aspects of a test method and equipment so as to improve the relevance of the inhalation preparation in-vivo and in-vitro test and expect that the in-vitro test method and the in-vitro test equipment can partially replace animal experiments or human clinical experiments.
At present, the in-vitro test of the inhaled preparation is specified according to Chinese pharmacopoeia 0951, and the determination of the aerodynamic characteristics of the fine particles of the preparation is the most important except the inhalation consistency test. The method mainly comprises the following three steps: device 1-two stage impactor; device 2-multistage impinger; plant 3-cascade impactor (NGI);
the current application range is widest, the most used is the device 3-cascade impactor, which consists of 7 stages and 1 micropore collector (MOC) cascade impactor, the whole cascade impactor is connected to a vacuum pump for providing constant suction flow, and suction agents enter the cascade impactor through an inlet and are deposited in an L-shaped connecting pipe, a pre-separator and 8 detachable collecting cups of the cascade impactor. Then, according to the instructions of the cascade impactor, the L-shaped connecting pipe, the pre-separator and the 8 collecting cups of the cascade impactor are cleaned by using a specified solution and are quantitatively diluted, then the dosage of the solution in the L-shaped connecting pipe, the pre-separator and the 8 collecting cups is measured by a specified analysis method, and then the cumulative fine particle dosage of a specified level can be obtained by aerodynamic calculation.
The disadvantages of the cascade impactors currently available are:
first, the existing cascade impactor only adopts an L-shaped connecting pipe with one size to replace the human body croup structure in an idealized mode, the difference between the human body croup structure and the actual human body croup structure is obvious, and the difference between the respiratory tract structures of different ages, sexes, race, medical history and the like is large, so that the existing cascade impactor cannot represent different groups of people.
Second, the existing cascade impactor directly adopts an L-shaped connecting pipe to replace the human body croup structure in an idealized manner, and does not consider the change of the respiratory tract structure under different respiratory states. The human body is in different respiratory states, and oral cavity volume, tongue position, glottis size etc. all are different, so current L type connecting pipe can not cover all different respiratory states.
Thirdly, the existing cascade impactor adopts a vacuum pump as a device for providing negative pressure, and can only test the deposition condition of preparation particles under constant flow, but the real situation is that the respiratory flow difference of a human body is huge when the human body uses a drug delivery device to inhale the preparation, and the deposition of the preparation in a respiratory tract is closely related to the respiratory flow, so that the existing cascade impactor can not simulate the result of the real respiratory flow change of the human body.
Fourth, the use of a vacuum pump as a means of providing negative pressure only tests for formulation deposition in the inspiratory state and not for the effect of the expiratory state on deposition.
Fifthly, the result of the aerodynamic characteristic determination of the fine particles of the preparation by adopting the cascade impactor is the specified fine particle accumulated mass of the preparation in the cascade impactor, meanwhile, the deposition amount with the aerodynamic diameter smaller than 5um is used as an important index for evaluating the inhaled preparation by the technology, and the particles with the aerodynamic diameter smaller than 5um can enter the deep lung and be absorbed by a human body; however, the fact that particles with an aerodynamic diameter greater than 5um may enter the deep lung and be absorbed by the human body, and particles with an aerodynamic diameter less than 5um may only be deposited in the croup region but not enter the deep lung, makes the determination of the aerodynamic properties of the fine particles of the formulation using a cascade impactor not perfectly compatible with in vivo tests.
Sixth, inhalation formulations for the treatment of various diseases require deposition of drug particles at various locations in the respiratory tract, such as the upper respiratory tract, bronchi, etc., and the aerodynamic characterization of fine particles of the formulations using cascade impactors does not allow for the testing of the deposition of the formulations at various locations in the respiratory tract.
SUMMERY OF THE UTILITY MODEL
In view of the above, in order to solve the above drawbacks of the aerodynamic property measurement of the fine particles of the formulation by using the cascade impactor, the present invention provides a testing method and apparatus for improving the in vivo and in vitro correlation of the inhaled formulation, which has the following advantages: the method has the advantages that the real respiratory tract model of the human body is adopted, the groups of the human body are carried out according to different ages, sexes, race and medical history, and the inhalation preparation deposition evaluation can be carried out on different groups of people. The method has the advantages that the key parts and characteristic factors of the respiratory tract structures of different populations and different respiratory tract states are classified, and inhalation preparation deposition evaluation can be performed on different respiratory tract structures. The invention adopts the piston type device as the breathing gas source, can carry out different breathing modes of single time and multiple cycles, including expiration, inspiration and breathing gas, and can realize the breathing state simulation of constant flow and real breathing curve. The invention can realize real-time measurement of the breathing curve and convert the breathing curve into piston motion to reduce the breathing process in real time. The novel quick-connection type croup model has the advantages that the novel quick-connection type croup model is adopted, not only can a large number of different fine parts of different respiratory tracts be accurately measured, but also a part of an integral part of the assembled respiratory tract can be quickly measured, meanwhile, the accuracy of the different fine parts and the quick measurement of the integral part are taken into consideration, and the novel quick-connection type croup model is suitable for different test scenes and requirements.
A test device for improving in vivo and in vitro correlation of an inhaled formulation comprising: the respiratory simulator comprises a drug administration device 1, a human respiratory tract model 2 and a respiratory simulator 3, wherein the human respiratory tract model 2 comprises an adapter 21, a real human respiratory tract 3D solid model 22 (also called as a "real human respiratory tract model" or an "artificial lung"), and the respiratory simulator 3 comprises a connection control component 31, a piston type movement device 32, a control system 33 and a respiratory data acquisition device 34, and is characterized in that: one end of the adapter 21 is connected with the drug delivery device 1, and the other end is connected with the real human respiratory tract 3D solid model 22, and the connection part can be ensured to be tightly attached; the real human body respiratory tract 3D solid model 22 is provided with a plurality of first quick-connection interfaces 221, the plurality of first quick-connection interfaces 221 are finally converged into a total gas path through a plurality of gas paths and then are connected to the inlet end of the connection control assembly 31, and the outlet end of the connection control assembly 32 is connected to the piston type locomotor 32; the connection control component 31 comprises a first electromagnetic valve 311, a second electromagnetic valve 312, a third electromagnetic valve 313, an electronic flowmeter 315 and a main body gas path, wherein the first electromagnetic valve 311 is arranged at the inlet end of the main body gas path of the connection control component 31, the electronic flowmeter 315 is positioned on the main body gas path and is positioned between the first electromagnetic valve 311 and the third electromagnetic valve 313, and the outlet end of the main body gas path is connected to the piston type movement device 32; a branch is arranged on the main body gas path between the third electromagnetic valve 313 and the piston type movement device 32, a second electromagnetic valve 312 is arranged on the branch, and the tail end of the branch is communicated with the atmosphere; the piston type movement device 32, the first electromagnetic valve 311, the second electromagnetic valve 312, the third electromagnetic valve 313 and the electronic flow meter 315 are electrically connected with the control system 33 through data communication lines; the control system 33 and the respiratory data acquisition device 34 are electrically connected through a data communication line.
Further, the main body air passage is connected to the inlet of the piston type mover 32 through the second quick-connect interface 321.
Further, the connection control module 31 further includes an electronic pressure gauge 314, which can be used to determine the sealing performance of the test device for improving the correlation between the inhaled formulation in vivo and in vitro, the better the sealing performance is, the more accurate the data of the test device for improving the correlation between the inhaled formulation in vivo and in vitro is, the higher the correlation is.
Further, the electronic pressure gauge 314 is electrically connected to the control system 33 via a data communication line.
Further, the real human respiratory tract 3D solid model 22 includes a nasal cavity and mouth-throat model 222, an epiglottis model 223, a main bronchus model 224, a terminal bronchus model 225 and an alveolus model 226, the real human respiratory tract 3D solid model 22 may adopt the existing real human respiratory tract 3D solid model on the market, the better the sealing performance of the real human respiratory tract 3D solid model is, the more accurate the data of the test equipment for improving the in-vitro correlation of the inhaled preparation is, the higher the correlation is.
Further, the first quick connect interface 221 is connected to the main bronchus model 224, the terminal bronchus model 225, and the alveolar model 226.
Further, the test equipment for improving the in vivo and in vitro correlation of the inhalation preparation is judged to have good sealing performance by the following indexes: the second electromagnetic valve 312 is closed, the third electromagnetic valve 313 is opened, the piston of the piston type mover 32 moves rightwards for a certain distance, negative pressure of-10 kpa is formed in the pipeline and then keeps static, and the pressure change in 10s is less than or equal to 0.5kpa, so that the sealing performance is judged to be good.
Further, the piston type mover 32 includes a servo motor, a servo controller, a power supply, a motion control board card and software therein, when the power supply supplies power to the servo motor and the servo controller, the control system 33 sends a signal to the software in the piston type mover 32, then drives the motion control board card through the software, then drives the servo controller through the software control board card, and finally drives the servo motor to move through the servo controller, thereby driving the piston to move back and forth left and right.
Further, the flow rate of the exhalation or inhalation of the breathing simulator 3 can be controlled by controlling the speed of the piston moving back and forth left and right, and normally, the flow rate of the exhalation or inhalation is controlled to be 0-120L/min, and the simulated flow rate of the exhalation or inhalation basically covers the flow rate of the exhalation or inhalation of a normal human under different physiological conditions.
Furthermore, the breathing simulator can simulate the single expiration state, the single inspiration state and the breathing state of the human body.
When a single suction state is simulated, the first solenoid valve 311 is open, and when the third solenoid valve 313 is open and the second solenoid valve 312 is closed, the piston moves from left to right in the piston type mover 32, which is a suction state; when the second solenoid valve 312 is open and the third solenoid valve 313 is closed, the flow of air pushed out of the right to left by the breathing simulator is directly vented to the atmosphere through the branch as the piston moves from right to left in the piston-type mover 32.
When the single exhalation state is simulated, the first solenoid valve 311 is open, and when the third solenoid valve 313 is open and the second solenoid valve 312 is closed, the piston moves from right to left in the piston type mover 32, which is the exhalation state; when the second electromagnetic valve 312 is opened and the third electromagnetic valve 313 is closed, and the piston moves from left to right in the piston type mover 32, air is sucked into the piston type mover 32 from the atmosphere through the branch, and the preparation deposition amount in the 3D solid model of the real human respiratory tract is not influenced.
When the breathing gas state is simulated, the first electromagnetic valve 311 is opened, the third electromagnetic valve 313 is opened, the second electromagnetic valve 312 is closed, and when the piston moves from left to right in the piston type movement 32, the breathing gas state is established; when the piston moves from right to left in the piston mover 32, it is in an expiratory state.
Further, the testing of the formulation deposition amounts of the individual components of the 3D physical model of the real human respiratory tract comprises two tests, the first being a separate test for each component and the second being a test for the individual components in assembled form as a unitary component.
Further, the control system 33 includes two control modes, which are: a real-time motion mode and a test mode of storing a breathing curve and running after delay are adopted, and the two modes can be switched at will; in the real-time movement mode, after the control system 33 collects the exhalation and/or inhalation signals generated by the respiration data collection device 34 and processes the signals, it will immediately send control signals to the first solenoid valve 311, the second solenoid valve 312, the third solenoid valve 313 and the piston motor 32, and control the open and close states of the first solenoid valve 311, the second solenoid valve 312 and the third solenoid valve 313, and control the piston of the piston motor 32 to move to the left or to the right, and the speed of the piston movement. In the delayed operation test mode of saving the breathing curve, after the control system 33 acquires that the breathing data acquisition device generates an expiration signal and/or an inspiration signal, the signals are processed and retained, and then a manual input signal is waited to trigger the first solenoid valve 311, the second solenoid valve 312, the third solenoid valve 313 and the piston type motor 32 to execute corresponding actions.
Further, the test device for improving in-vivo and in-vitro correlation of the inhaled preparation further comprises a quantitative test instrument 4, which can be used for calibrating the deposition amount of the preparation at each part of the 3D solid model 22 of the real human respiratory tract.
Further, the quantitative test instrument 4 comprises a high performance liquid chromatograph, a high precision balance, a radioactive element calibration instrument, and the like. When a high performance liquid chromatograph is adopted, the adopted quantitative method is a liquid chromatography, the test is carried out according to a preparation inhalation test method specified by pharmacopoeia, each component of the real human respiratory tract 3D solid model after the operation is cleaned by blank receiving liquid, the volume is quantitatively diluted to a certain volume, and the amount of active substances in each part of solution is respectively measured according to a method specified by the pharmacopoeia, so that the preparation deposition amount of each component of the real human respiratory tract 3D solid model can be obtained. When a high-precision daily time is adopted, the adopted quantitative method is a weighing method, and the deposition amount of each component of the real human respiratory tract 3D solid model can be calculated by subtracting the mass of each component of the real human respiratory tract 3D solid model before spraying from the mass of each component of the real human respiratory tract 3D solid model after spraying the preparation. When a radioactive element calibration instrument is adopted, the adopted quantitative method is a radioactive ray imaging method, radioactive fluorescent substances are added into the inhalation preparation, and after the preparation is sprayed, the radioactive intensity of each component of the real human respiratory tract 3D solid model is shot by using radiation imaging, so that the deposition amount of the preparation is calculated.
Further, the working process of the test device for improving the in vivo and in vitro correlation of the inhaled preparation is as follows: firstly, the respiratory data acquisition device 34 acquires the expiratory and/or inspiratory flow rate data of the human body, and then the flow rate data is transmitted to the control system, the control system gives out a control signal after analysis, and controls the opening and closing of the first electromagnetic valve 311, the second electromagnetic valve 312, the third electromagnetic valve 313, and the movement direction and speed of the piston type locomotor 32, so as to simulate the expiratory and/or inspiratory condition of the lung of the human body, at this time, the electronic pressure gauge 314 transmits the detected pressure data to the control system 33 in real time, the electronic flow meter 315 transmits the detected gas flow data to the control system 33 in real time, the control system 33 continuously traces a real-time respiratory curve, and continuously compares with the respiratory curve transmitted by the respiratory data acquisition device 34, continuously adjusts and approaches in real time, and simulates the most real respiratory state, meanwhile, the preparation in the drug delivery device 1 enters the real human respiratory tract 3D solid model 22 and is deposited at different positions; after the simulated respiratory state is finished, the preparation deposition amount in each component of the 3D solid model 22 of the real human respiratory tract is measured by the quantitative testing instrument 4.
Drawings
FIG. 1 is a schematic diagram of the structure of the test device for improving in-vivo and in-vitro correlation of an inhaled preparation according to the invention.
Fig. 2 is a schematic structural diagram of a real human respiratory tract 3D solid model.
FIG. 3 is an enlarged schematic view of the main bronchus model, the terminal bronchus model, and the alveolar model of the 3D physical model of the real human respiratory tract.
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| Human |
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21 |
| Real human respiratory tract 3D |
22 |
| First quick- |
221 |
| Nasal cavity and oral cavity model | 222 |
| Epiglottis model | 223 |
| Main bronchus model | 224 |
| End bronchus model | 225 |
| Alveolar model | 226 |
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3 |
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31 |
| First |
311 |
| Second |
312 |
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313 |
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314 |
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315 |
| Piston type |
32 |
| Second quick- |
321 |
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33 |
| Respiratory |
34 |
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4 |
The drawings are described in detail below with reference to specific embodiments.
Detailed Description
Specific embodiment example 1:
FIG. 1 is a schematic diagram of the test device for improving in vivo and in vitro correlation of inhaled preparations according to the present invention; fig. 2 is a schematic structural diagram of a 3D physical model of a real human respiratory tract. A test device for improving in vivo and in vitro correlation of an inhaled formulation comprising: dosing unit 1, human respiratory tract model 2 and breathing analog machine 3, wherein human respiratory tract model 2 includes adapter 21, real human respiratory tract 3D solid model 22, and breathing analog machine 3 includes connection control subassembly 31, piston locomotory apparatus 32, control system 33 and breathing data acquisition device 34, its characterized in that: one end of the adapter 21 is connected with the drug delivery device 1, and the other end is connected with the real human respiratory tract 3D solid model 22, and the connection part can be ensured to be tightly attached; the real human body respiratory tract 3D solid model 22 is provided with a plurality of first quick-connection interfaces 221, the plurality of first quick-connection interfaces 221 are finally converged into a total gas path through a plurality of gas paths and then are connected to the inlet end of the connection control assembly 31, and the outlet end of the connection control assembly 32 is connected to the piston type locomotor 32; the connection control component 31 comprises a first electromagnetic valve 311, a second electromagnetic valve 312, a third electromagnetic valve 313, an electronic flowmeter 315 and a main body gas path, wherein the first electromagnetic valve 311 is arranged at the inlet end of the main body gas path of the connection control component 31, the electronic flowmeter 315 is positioned on the main body gas path and is positioned between the first electromagnetic valve 311 and the third electromagnetic valve 313, and the outlet end of the main body gas path is connected to the piston type movement device 32; a branch is arranged on the main body gas path between the third electromagnetic valve 313 and the piston type movement device 32, a second electromagnetic valve 312 is arranged on the branch, and the tail end of the branch is communicated with the atmosphere; the piston type movement device 32, the first electromagnetic valve 311, the second electromagnetic valve 312, the third electromagnetic valve 313 and the electronic flow meter 315 are electrically connected with the control system 33 through data communication lines; the control system 33 and the respiratory data acquisition device 34 are electrically connected through a data communication line.
The body gas line is connected to the inlet of the piston mover 32 through a second quick connect interface 321.
The connection control module 31 further includes an electronic pressure gauge 314, which can be used to determine the sealing performance of the test device for improving the correlation between the inhaled formulation in vivo and in vitro, the better the sealing performance is, and the more accurate the data of the test device for improving the correlation between the inhaled formulation in vivo and in vitro is, the higher the correlation is.
The electronic pressure gauge 314 is electrically connected to the control system 33 via a data communication line.
The real human respiratory tract 3D solid model 22 comprises a nasal cavity and oral larynx model 222, an epiglottis model 223, a main bronchus model 224, a terminal bronchus model 225 and an alveolus model 226, the real human respiratory tract 3D solid model 22 can adopt the existing real human respiratory tract 3D solid model on the market, the better the sealing performance of the real human respiratory tract 3D solid model is, the more accurate the data of the test equipment for improving the in-vitro correlation of the inhaled preparation in vivo is, and the higher the correlation is.
The first quick connect interface 221 is connected to the main bronchus model 224, the terminal bronchus model 225, and the alveolar model 226.
The test equipment for improving the in-vivo and in-vitro correlation of the inhalation preparation is judged to have good sealing performance by the following indexes: the second electromagnetic valve 312 is closed, the third electromagnetic valve 313 is opened, the piston of the piston type mover 32 moves rightwards for a certain distance, negative pressure of-10 kpa is formed in the pipeline and then keeps static, and the pressure change in 10s is less than or equal to 0.5kpa, so that the sealing performance is judged to be good.
The piston type mover 32 comprises a servo motor, a servo controller, a power supply, a motion control board card and software, when the power supply supplies power to the servo motor and the servo controller, the control system 33 sends a signal to the software in the piston type mover 32, then the motion control board card is driven by the software, then the servo controller is driven by the software control board card, and finally the servo motor is driven by the servo controller to move, so that the piston is driven to move left and right.
The flow rate of the exhalation or the inhalation of the breathing simulator 3 can be controlled by controlling the speed of the piston moving back and forth left and right, usually, the flow rate of the exhalation or the inhalation is controlled to be 0-120L/min, and the simulated flow rate of the exhalation or the inhalation basically covers the flow rate of the exhalation or the inhalation of a normal human under different physiological states.
The breathing simulator can simulate the independent expiration state, the independent inspiration state and the breathing gas state of a human body.
When a single suction state is simulated, the first solenoid valve 311 is open, and when the third solenoid valve 313 is open and the second solenoid valve 312 is closed, the piston moves from left to right in the piston type mover 32, which is a suction state; when the second solenoid valve 312 is open and the third solenoid valve 313 is closed, the flow of air pushed out of the right to left by the breathing simulator is directly vented to the atmosphere through the branch as the piston moves from right to left in the piston-type mover 32.
When the single exhalation state is simulated, the first solenoid valve 311 is open, and when the third solenoid valve 313 is open and the second solenoid valve 312 is closed, the piston moves from right to left in the piston type mover 32, which is the exhalation state; when the second electromagnetic valve 312 is opened and the third electromagnetic valve 313 is closed, and the piston moves from left to right in the piston type mover 32, air is sucked into the piston type mover 32 from the atmosphere through the branch, and the preparation deposition amount in the 3D solid model of the real human respiratory tract is not influenced.
When the breathing gas state is simulated, the first electromagnetic valve 311 is opened, the third electromagnetic valve 313 is opened, the second electromagnetic valve 312 is closed, and when the piston moves from left to right in the piston type movement 32, the breathing gas state is established; when the piston moves from right to left in the piston mover 32, it is in an expiratory state.
The testing of the amount of formulation deposited for each component of a 3D physical model of a real human respiratory tract comprises two tests, the first being a separate test for each component and the second being a test for each component in assembled form as a unitary component.
The control system 33 includes two control modes, which are: a real-time motion mode and a test mode of storing a breathing curve and running after delay are adopted, and the two modes can be switched at will; in the real-time movement mode, after the control system 33 collects the exhalation and/or inhalation signals generated by the respiration data collection device 34 and processes the signals, it will immediately send control signals to the first solenoid valve 311, the second solenoid valve 312, the third solenoid valve 313 and the piston motor 32, and control the open and close states of the first solenoid valve 311, the second solenoid valve 312 and the third solenoid valve 313, and control the piston of the piston motor 32 to move to the left or to the right, and the speed of the piston movement. In the delayed operation test mode of saving the breathing curve, after the control system 33 acquires that the breathing data acquisition device generates an expiration signal and/or an inspiration signal, the signals are processed and retained, and then a manual input signal is waited to trigger the first solenoid valve 311, the second solenoid valve 312, the third solenoid valve 313 and the piston type motor 32 to execute corresponding actions.
The test device for improving the in-vivo and in-vitro correlation of the inhaled preparation further comprises a quantitative test instrument 4 which can be used for calibrating the deposition amount of the preparation at each part of the 3D solid model 22 of the real human respiratory tract.
The quantitative test instrument 4 comprises a high performance liquid chromatograph, a high precision balance, a radioactive element calibration instrument and the like. When a high performance liquid chromatograph is adopted, the adopted quantitative method is a liquid chromatography, the test is carried out according to a preparation inhalation test method specified by pharmacopoeia, each component of the real human respiratory tract 3D solid model after the operation is cleaned by blank receiving liquid, the volume is quantitatively diluted to a certain volume, and the amount of active substances in each part of solution is respectively measured according to a method specified by the pharmacopoeia, so that the preparation deposition amount of each component of the real human respiratory tract 3D solid model can be obtained. When a high-precision daily time is adopted, the adopted quantitative method is a weighing method, and the deposition amount of each component of the real human respiratory tract 3D solid model can be calculated by subtracting the mass of each component of the real human respiratory tract 3D solid model before spraying from the mass of each component of the real human respiratory tract 3D solid model after spraying the preparation. When a radioactive element calibration instrument is adopted, the adopted quantitative method is a radioactive ray imaging method, radioactive fluorescent substances are added into the inhalation preparation, and after the preparation is sprayed, the radioactive intensity of each component of the real human respiratory tract 3D solid model is shot by using radiation imaging, so that the deposition amount of the preparation is calculated.
The working process of the test device for improving the correlation between the inhaled preparation in vivo and in vitro is as follows: firstly, the respiratory data acquisition device 34 acquires the expiratory and/or inspiratory flow rate data of the human body, and then the flow rate data is transmitted to the control system, the control system gives out a control signal after analysis, and controls the opening and closing of the first electromagnetic valve 311, the second electromagnetic valve 312, the third electromagnetic valve 313, and the movement direction and speed of the piston type locomotor 32, so as to simulate the expiratory and/or inspiratory condition of the lung of the human body, at this time, the electronic pressure gauge 314 transmits the detected pressure data to the control system 33 in real time, the electronic flow meter 315 transmits the detected gas flow data to the control system 33 in real time, the control system 33 continuously traces a real-time respiratory curve, and continuously compares with the respiratory curve transmitted by the respiratory data acquisition device 34, continuously adjusts and approaches in real time, and simulates the most real respiratory state, meanwhile, the powdery preparation in the drug delivery device 1 enters the real human respiratory tract 3D solid model 22 and deposits are generated at different positions; after the simulated respiratory state is finished, the preparation deposition amount in each component of the 3D solid model 22 of the real human respiratory tract is measured by the quantitative testing instrument 4.
The above-mentioned embodiments only express several 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. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. A test device for improving in vivo and in vitro correlation of an inhaled formulation comprising: dosing unit (1), human respiratory tract model (2) and breathing analog machine (3), wherein human respiratory tract model (2) include adapter (21), real human respiratory tract 3D solid model (22), and breathing analog machine (3) are including connection control subassembly (31), piston locomotory apparatus (32), control system (33) and breathing data acquisition device (34), its characterized in that: one end of the adapter (21) is connected with the drug delivery device (1), and the other end of the adapter is connected with the real human respiratory tract 3D solid model (22), and the connection part can be ensured to be tightly attached; a plurality of first quick-connection interfaces (221) are arranged on the real human body respiratory tract 3D solid model (22), the plurality of first quick-connection interfaces (221) are finally converged into a total air path through a plurality of air paths and then are connected to the inlet end of the connection control assembly (31), and the outlet end of the connection control assembly (31) is connected to the piston type locomotor (32); the connection control assembly (31) comprises a first electromagnetic valve (311), a second electromagnetic valve (312), a third electromagnetic valve (313), an electronic flow meter (315) and a main body gas circuit, wherein the first electromagnetic valve (311) is arranged at the inlet end of the main body gas circuit of the connection control assembly (31), the electronic flow meter (315) is positioned on the main body gas circuit and is positioned between the first electromagnetic valve (311) and the third electromagnetic valve (313), and the outlet end of the main body gas circuit is connected to the piston type movement device (32); a branch is arranged on the main body gas path between the third electromagnetic valve (313) and the piston type locomotory apparatus (32), a second electromagnetic valve (312) is arranged on the branch, and the tail end of the branch is communicated with the atmosphere; the piston type movement device (32), the first electromagnetic valve (311), the second electromagnetic valve (312), the third electromagnetic valve (313) and the electronic flowmeter (315) are electrically connected with the control system (33) through data communication lines; the control system (33) is electrically connected with the respiration data acquisition device (34) through a data communication line.
2. The test device for enhancing the in vivo and in vitro correlation of an inhaled formulation according to claim 1, wherein: the main body air passage is connected with the inlet of the piston type movement device (32) through a second quick connection interface (321).
3. The test device for enhancing the in vivo and in vitro correlation of an inhaled formulation according to claim 1, wherein: the connection control component (31) also comprises an electronic pressure gauge (314).
4. A test device for enhancing the in vivo and in vitro correlation of an inhaled formulation according to claim 3, wherein: the electronic pressure gauge (314) is electrically connected with the control system (33) through a data communication line.
5. The test device for enhancing the in vivo and in vitro correlation of an inhaled formulation according to claim 1, wherein: the real human respiratory tract 3D solid model (22) comprises a nasal cavity and oral larynx model (222), an epiglottis model (223), a main bronchus model (224), a terminal bronchus model (225) and an alveolus model (226).
6. The test device for enhancing in vivo and in vitro correlation of an inhaled formulation according to claim 5, wherein: the first quick-connection interface (221) is connected to the main bronchus model (224), the tail-end bronchus model (225) and the alveolus model (226).
7. The test device for enhancing the in vivo and in vitro correlation of an inhaled formulation according to claim 1, wherein: the second electromagnetic valve (312) is closed, the third electromagnetic valve (313) is opened, a piston of the piston type mover (32) moves rightwards for a certain distance, negative pressure of-10 kpa is formed in the pipeline and then the pipeline is kept static, and when the pressure change in 10s is less than or equal to 0.5kpa, the sealing performance of the equipment is good.
8. The test device for enhancing the in vivo and in vitro correlation of an inhaled formulation according to claim 1, wherein: the piston type mover (32) includes inside: the power supply supplies power to the servo motor and the servo controller, the control system (33) sends a signal to software inside the piston type mover (32), then the software drives the motion control board, the servo controller is driven by the software control board, and the servo controller drives the servo motor to move to drive the piston to move left and right back and forth.
9. The test device for enhancing the in vivo and in vitro correlation of an inhaled formulation according to claim 1, wherein: the flow rate of expiration or inspiration of the breathing simulator (3) can be controlled by controlling the speed of the piston moving back and forth left and right, and the flow rate of expiration or inspiration is controlled to be 0-120L/min.
10. The test device for enhancing the in vivo and in vitro correlation of an inhaled formulation according to claim 1, wherein: the breathing simulator (3) can simulate the independent expiration state, the independent inspiration state and the breathing gas state of a human body.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110514384A (en) * | 2019-09-18 | 2019-11-29 | 苏州新劢德医药工程仿真技术有限公司 | A kind of test method and equipment improving in vitro correlation in sucking preparation body |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110514384A (en) * | 2019-09-18 | 2019-11-29 | 苏州新劢德医药工程仿真技术有限公司 | A kind of test method and equipment improving in vitro correlation in sucking preparation body |
| CN110514384B (en) * | 2019-09-18 | 2023-11-24 | 苏州新劢德医疗器械科技有限公司 | Test method and equipment for improving in-vivo and in-vitro correlation of inhalation preparation |
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Address after: Room 1901, Building B, No. 388 Ruoshui Road, Suzhou Industrial Park, Jiangsu Province, 215000 Patentee after: Suzhou Xinpu First Pharmaceutical Technology Co.,Ltd. Address before: Room 1901, Building B, No. 388 Ruoshui Road, Suzhou Industrial Park, Jiangsu Province, 215000 Patentee before: Suzhou Xinmai de Pharmaceutical Engineering Simulation Technology Co.,Ltd. |
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Effective date of registration: 20230105 Address after: Room E406-17, No. 388 Ruoshui Road, Suzhou Industrial Park, Suzhou Area, China (Jiangsu) Pilot Free Trade Zone, Suzhou City, Jiangsu Province, 215123 Patentee after: SUZHOU SINGMED MEDICAL DEVICE SCIENCE AND TECHNOLOGY Ltd. Address before: Room 1901, Building B, No. 388 Ruoshui Road, Suzhou Industrial Park, Jiangsu Province, 215000 Patentee before: Suzhou Xinpu First Pharmaceutical Technology Co.,Ltd. |