CN114236030A - Sample testing method and device for delivery rate and total delivery amount of inhalation preparation - Google Patents

Abstract

The application relates to a sample testing method and a testing device for the delivery rate and the total delivery amount of an inhalation preparation, wherein the method comprises the steps of arranging a filter membrane at a testing port of a breathing simulator; connecting the breathing simulator and the atomizer; taking a quantitative sample of the inhalation preparation, and putting the sample into a container communicated with an atomizer; starting the breathing simulator and the atomizer for setting time to ensure that the sample is atomized firstly and then passes through the filter membrane; taking down the filter membrane, taking the cleaning solvent, and carrying out quantitative leaching on the filter membrane to obtain leacheate; centrifuging the filter membrane to obtain a centrifugate; taking the centrifugal liquid, and mixing the centrifugal liquid with the obtained leacheate to obtain a mixed liquid; diluting the mixed solution to a constant volume to obtain a test solution; measuring measurement data corresponding to the amount of the inhaled formulation sample in the test solution; the rate of delivery and the total amount delivered of the sample are calculated from the measurement data obtained. The method and the device have the advantages of improving the delivery rate and the test efficiency of the total delivery amount test and improving the measurement precision.

Description

Sample testing method and device for delivery rate and total delivery amount of inhalation preparation

Technical Field

The application relates to the field of inhalation preparation sampling analysis, in particular to a sample testing method and a sample testing device for the delivery rate and the total delivery amount of an inhalation preparation.

Background

At present, an inhalation preparation refers to a liquid preparation for an atomizer and also refers to a special dosage form for pulmonary administration, and the medicine can rapidly and directly enter the lung to play the drug effect by a local administration mode, so that the administration dosage is reduced, and the curative effect of the medicine is improved. Inhalation formulations can be classified into Dry Powder Inhalers (DPI), aerosols (MDI), nebulized inhalation solutions (NEB), and sprays according to their device differences.

According to the current pharmacopoeia of China, the determination of the delivery rate and the total delivery amount of the inhaled liquid preparation is required, wherein the treatment mode of the inhaled liquid preparation collected for testing in the process of simulating the delivery process is included, and the detection result of the delivery rate and the total delivery amount can be directly influenced. At present, a common practice in a laboratory is to generate negative pressure through a vacuum pump to absorb an inhaled preparation sample subjected to atomization treatment, wherein aerosol of the inhaled preparation sample passes through a filter membrane and remains on the filter membrane, the filter membrane is rinsed with a solvent and then is manually squeezed and eluted for multiple times, and the content of the inhaled preparation sample is measured after eluent is collected.

Aiming at the related technologies, the inventor thinks that the manual extrusion of the elution filter membrane is repeated, the time and the labor are wasted, the individual difference is large, and the measurement error is large.

Disclosure of Invention

In a first aspect, the present application provides a sample testing method for inhalation formulation delivery rate and total delivery amount in order to improve testing efficiency and measurement accuracy of the delivery rate and total delivery amount test.

The application provides a sample test method for delivery rate and total delivery amount of an inhalation preparation, which adopts the following technical scheme:

a sample testing method for inhalation formulation delivery rate and total delivered amount comprising:

arranging a filter membrane at a test port of the breathing simulator;

connecting the breathing simulator and the atomizer;

taking a quantitative sample of the inhalation preparation, and putting the sample into a container communicated with an atomizer;

starting the breathing simulator and the atomizer for setting time to ensure that the sample is atomized firstly and then passes through the filter membrane;

taking down the filter membrane, taking the cleaning solvent, and carrying out quantitative leaching on the filter membrane to obtain leacheate;

centrifuging the filter membrane to obtain a centrifugate;

taking the centrifugal liquid, and mixing the centrifugal liquid with the obtained leacheate to obtain a mixed liquid;

diluting the mixed solution to a constant volume to obtain a test solution;

measuring measurement data corresponding to the amount of the inhaled formulation sample in the test solution;

the rate of delivery and the total amount delivered of the sample are calculated from the measurement data obtained.

By adopting the technical scheme, the breathing simulator can simulate the breathing rhythm of a human body, so that the real effect of the inhalation preparation in actual use aiming at the human body can be verified, and the data has stronger referential property; the atomizer atomizes a drug sample of an inhalation preparation to form aerosol particles, and then the aerosol particles pass through a filter membrane under the negative pressure action of a breathing simulator, so that the components of the drug sample can be retained on the filter membrane, the filter membrane is rinsed firstly, part of the drug components are transferred into a rinsing solution, the filter membrane is subjected to centrifugal treatment, the rest of the drug components are transferred into a centrifugate through centrifugal motion, and finally the mixture is mixed to obtain a mixed solution, and the content of the drug sample in the mixed solution is measured through a liquid chromatograph, so that the data such as the delivery rate and the total delivery amount of the inhalation preparation can be obtained, and the measurement precision is improved.

Preferably, after the step of taking the cleaning solvent and quantitatively rinsing the filter membrane, the method further comprises the following steps:

soaking the filter membrane in a soaking solvent to obtain a soaking solution;

extruding the filter membrane to obtain an extrusion liquid;

mixing the obtained soaking solution and the obtained extrusion solution into the mixed solution;

diluting the mixed solution to a constant volume to obtain the test solution.

By adopting the technical scheme, part of the medicine components possibly permeate into the filter membrane and are firmly adhered, so that the filter membrane is soaked by the soaking solvent, the part of the medicine components are separated, and the measurement accuracy of data such as the delivery rate and the total delivery amount of the inhalation preparation is improved.

Preferably, the centrifugation treatment comprises:

putting the filter membrane into a centrifuge tube, putting the centrifuge tube into a centrifuge, and setting the centrifugation rate and time parameters;

and taking the liquid in the centrifugal tube, and mixing the liquid with the obtained leacheate to obtain a mixed solution.

By adopting the technical scheme, residual water and drug components in the filter membrane are stripped out through the centrifugal motion of the centrifugal machine, so that the measurement accuracy of data such as the delivery rate and the total delivery amount of the inhalation preparation is improved.

Preferably, the centrifuging tube includes the collecting pipe and is used for placing the chimney filter of filter membrane, the collecting pipe cup joints outside the chimney filter, it has the filtration pore to distribute on the chimney filter, the degree of depth of collecting pipe is greater than the chimney filter.

Through adopting above-mentioned technical scheme, in the centrifugal motion in-process, the drug composition that throws away on chimney filter separation filter membrane and the filter membrane to modes such as this traditional extrusion wringing relatively can reduce the deformation of filter membrane, and convenient used repeatedly promotes separation efficiency simultaneously.

In order to improve the testing efficiency and the measuring accuracy of the delivery rate and the total delivery amount test, the application provides a testing device for implementing the sample testing method of the delivery rate and the total delivery amount of the inhalation preparation, and the following technical scheme is adopted:

the utility model provides a testing arrangement, includes atomizer, breathing simulator, first atomizing pipe and second atomizing pipe, atomizer, first atomizing pipe, second atomizing pipe and breathing simulator communicate in proper order, the filter membrane is placed between first atomizing pipe and second atomizing pipe, first atomizing pipe can dismantle with the second atomizing pipe and be connected.

Through adopting above-mentioned technical scheme, it is fixed to the filter membrane centre gripping through first atomizing pipe and second atomizing pipe, and first atomizing pipe can dismantle with the second atomizing pipe and be connected to this conveniently takes out the filter membrane and carries out treatments such as drip washing, centrifugation.

Preferably, be connected with first stationary blade on the first atomizing pipe, be connected with the second stationary blade on the second atomizing pipe, the slot has been seted up on the second atomizing pipe, first atomizing pipe and slot grafting cooperation, first stationary blade passes through the screw with the second stationary blade and fixes when both fix first atomizing pipe and second atomizing pipe are fixed.

Through adopting above-mentioned technical scheme, the side direction skew of inserting of slot and first atomizing pipe is joined in marriage and reducible first atomizing pipe, and first stationary blade and second stationary blade then can restrict the axial skew of first atomizing pipe and second atomizing pipe.

Preferably, a film outlet is formed in the side wall of the second atomizing pipe, a sliding channel communicated with the film outlet is formed in the second atomizing pipe, a support is arranged in the sliding channel in a sliding manner along the radial direction of the second atomizing pipe, and the support is used for placing a filter membrane;

the sliding channel is communicated with the slot, the first atomizing pipe is abutted to the support when inserted into the slot, and the filter membrane covers the opening of the first atomizing pipe.

Through adopting above-mentioned technical scheme, can realize the business turn over of support in the second atomizing pipe through sliding channel, when the second atomizing pipe was put into to the support, first atomizing pipe insert in the slot and with the support butt, the filter membrane covers the opening of first atomizing pipe to this makes the atomizing medicine sample accessible filter membrane collect, and slidable support takes out the filter membrane after the experiment, thereby conveniently carries out operations such as drip washing.

Preferably, an elastic part is arranged on the second atomizing pipe, one end of the elastic part is connected with the second atomizing pipe, and the other end of the elastic part is connected with the bracket;

the screw is including wearing to locate the double-screw bolt on the first stationary blade, the axial of double-screw bolt with the direction of first atomizing pipe insertion slot is unanimous, double-screw bolt and second stationary blade threaded connection.

Through adopting above-mentioned technical scheme, but make the support auto-eject go out the membrane mouth through elastic component, and the double-screw bolt can make the tight support of first atomizing pipe pressure, avoids support auto-eject among the test process, plays the locking action.

Preferably, the holder comprises a fixing ring and a support ring, the fixing ring being parallel to the radial section of the second nebulization tube;

be connected with elastic connecting portion between solid fixed ring and the support ring, elastic connecting portion are used for the solid fixed contained angle of ring and support ring of increase, just the filter membrane is placed on solid fixed ring, works as the support ring rotates and is close to the edge that solid fixed ring pressed from both sides tight filter membrane when solid fixed ring.

By adopting the technical scheme, when the support is automatically popped out of the membrane outlet, the support ring moves under the elastic action of the elastic connecting part to increase the included angle between the support ring and the fixing ring, so that the filter membrane is obliquely placed, the filter membrane is prevented from falling off, and meanwhile, the support is convenient for workers to clamp; when the support is plugged into the sliding channel, the support ring is close to the fixing ring under the pushing action of the edge of the film outlet, then the edge of the filter membrane is clamped by matching with the fixing ring, and the support ring is pressed tightly when the first atomizing pipe is plugged, so that the sealing performance is improved.

Preferably, a temperature sensing element for detecting the temperature in the first atomization tube is arranged in the first atomization tube, the temperature sensing element is connected with a controller, and a temperature control element is arranged outside the first atomization tube and/or the second atomization tube;

the controller is used for acquiring the air temperature in the pipe and controlling the temperature control piece to operate according to the air temperature in the pipe so as to enable the air temperature in the pipe to be always lower than or equal to the air temperature outside the pipe.

By adopting the technical scheme, the temperature inside and outside the first atomization pipe and the second atomization pipe is adjusted through the temperature control part, so that the phenomenon that atomized medicine components are condensed on the pipe wall due to external cold and internal heat is avoided, and the accuracy of measuring the delivery efficiency is reduced.

In summary, the present application includes at least one of the following beneficial technical effects:

1. aerosol particles pass through a filter membrane under the negative pressure action of a breathing simulator, so that components of a medicine sample can be reserved on the filter membrane, the filter membrane is rinsed, part of medicine components are transferred into a rinsing liquid, the filter membrane is centrifuged, the rest of the medicine components are transferred into a centrifugate through centrifugal motion, finally a mixed solution is obtained through mixing, the content of the medicine sample in the mixed solution is measured through a liquid chromatograph, and then data such as delivery rate, total delivery amount and the like of an inhalation preparation can be obtained, so that the measurement precision is improved;

2. the residual moisture and the drug components in the filter membrane are stripped out through the centrifugal motion of the centrifugal machine, so that the measurement precision of data such as the delivery rate and the total delivery amount of the inhalation preparation is improved;

3. in the centrifugal motion process, the drug composition that throws away on filter membrane and the filter membrane is separated to the chimney filter to this mode such as traditional extrusion is wrung out relatively can reduce the deformation of filter membrane, makes things convenient for used repeatedly, promotes separation efficiency simultaneously.

Drawings

Figure 1 is a method flow chart of a sample testing method for inhalation formulation delivery rate and total delivered amount of example 1 of the present application.

Fig. 2 is a schematic view of the overall structure of the test apparatus according to embodiment 1 of the present application.

Fig. 3 is a partial structural schematic view of the testing device in embodiment 2 of the present application, mainly showing a filling tube.

Fig. 4 is a partial structural schematic diagram of the testing device of embodiment 3 of the present application, mainly showing through holes.

Fig. 5 is a schematic view of the overall structure of the test apparatus according to embodiment 4 of the present application.

Fig. 6 is a partial structural schematic view of the testing device of embodiment 4 of the present application, mainly showing a bracket.

Description of reference numerals: 1. a breathing simulator; 11. filtering the membrane; 12. an atomizer; 13. an atomizing cup; 2. a first atomization tube; 21. a temperature sensing element; 22. a first fixing sheet; 23. a stud; 3. a second atomization tube; 31. a slot; 32. a slide channel; 33. a second fixing sheet; 4. a support; 41. a fixing ring; 411. an annular groove; 42. a support ring; 43. an elastic connection portion; 5. a fill tube; 51. a through hole; 6. a guide post; 61. a slider; 62. an elastic member; 63. and a nut.

Detailed Description

The present application is described in further detail below with reference to the accompanying drawings.

Example 1:

referring to fig. 1, 2, a sample test method for inhalation formulation delivery rate and total amount delivered includes the steps of:

firstly, preparing a breathing simulator 1, a filter membrane 11, an atomizer 12, an atomizing cup 13, a volumetric flask, a soaking cup, a centrifuge tube, a centrifuge and a plurality of beakers;

s1, arranging a filter membrane 11 at the test port of the breathing simulator 1, connecting the breathing simulator 1 and the atomizer 12, and communicating the liquid inlet of the atomizer 12 with the atomizing cup 13.

Specifically, both sides of the filter membrane 11 are respectively in sealed communication with the test port of the breathing simulator 1 and the outlet of the atomizer 12, and the filter membrane 11 may be a gas-permeable filter membrane 11 capable of filtering aerosol, such as an ultrafiltration membrane.

S2, placing a certain amount of the sample of the inhalation preparation into the atomizing cup 13, then setting parameters such as the breathing frequency and the operation time of the breathing simulator 1, and setting the operation time of the atomizer 12, wherein the operation time of the breathing simulator 1 is consistent with the operation time of the atomizer 12.

And S3, starting the breathing simulator 1 and the atomizer 12 simultaneously, so that the sample is atomized firstly and then passes through the filter membrane 11.

And S4, after the breathing simulator 1 and the atomizer 12 stop, taking down the filter membrane 11, taking the cleaning solvent, and carrying out quantitative leaching on the filter membrane 11 to obtain the leacheate.

Specifically, the cleaning solvent can be a solvent which has high solubility relative to the inhalation preparation and does not react with the inhalation preparation, and specifically needs to be adjusted according to different inhalation preparations, the leaching amount can be 10-25ml, and the leaching solution obtained after leaching is stored in a beaker.

S5, taking the soaking solvent, soaking the filter membrane 11 to obtain a soaking solution, extruding the filter membrane 11 to obtain an extruding solution, and putting the soaking solution and the extruding solution into a beaker.

Specifically, the soaking solvent can be the same as the cleaning solvent, the filter membrane 11 can be fully soaked by a glass rod during soaking, the soaking time can be 2-10min, so that the filter membrane 11 is fully wetted, and the firmly adhered medicinal components can permeate out.

S6, placing the filter membrane 11 into an inner layer filter tube of a centrifuge tube, placing the centrifuge tube into a centrifuge, setting the centrifugation speed and time parameters, carrying out centrifugation treatment to obtain a centrifugate, and placing the centrifugate into a beaker.

The centrifugal tube used in the step S6 is divided into two layers, and comprises a collecting tube and a filter tube for placing the filter membrane 11, wherein the collecting tube is sleeved outside the filter tube, and the depth of the collecting tube is larger than that of the filter tube. The last distribution of chimney filter has the filtration pore, and the filtration pore is used for getting into the collection intraductal collection with the sample that filter membrane 11 went up the centrifugation and throws away, and mode such as traditional extrusion wringing can reduce filter membrane 11's deformation, makes things convenient for used repeatedly, promotes separation efficiency simultaneously.

And S7, mixing the obtained leacheate, the soak solution, the squeezing solution and the centrifugate, putting the mixture into a volumetric flask to obtain a mixed solution, and diluting the mixed solution to a constant volume to obtain the test solution.

Specifically, the test solution contains the medicinal components separated after the filter membrane 11 is rinsed, soaked, extruded and centrifugally dried, and contains all aerosols of the sample obtained by filtering with the filter membrane 11 during the operation of the breathing simulator 1.

S8, measuring data corresponding to the content of the inhalation preparation sample in the test solution by a liquid chromatograph.

And S9, calculating the delivery rate and the total delivery amount of the sample according to the obtained measurement data.

Specifically, the worker can obtain the total delivery amount of the corresponding inhalation preparation according to the content of the sample separated from the filter membrane 11, and then the delivery efficiency of the corresponding inhalation preparation can be obtained by combining the running time and other parameters of the atomizer 12 and the breathing simulator 1.

For easy to assemble filter membrane 11, embodiment 1 still discloses a testing arrangement, and it includes atomizer 12, breathing simulator 1, first atomizing pipe 2 and second atomizing pipe 3, and atomizer 12, first atomizing pipe 2, second atomizing pipe 3 and breathing simulator 1 communicate in proper order, and the one end of second atomizing pipe 3 and the test mouth intercommunication of breathing simulator 1, slot 31 has been seted up to the other end of second atomizing pipe 3. First atomizing pipe 2 one end and the export intercommunication of atomizer 12, its other end and slot 31 grafting cooperation, and first atomizing pipe 2 passes through the bolt fastening with second atomizing pipe 3 to realize dismantling between first atomizing pipe 2 and the second atomizing pipe 3 and be connected. And the filter membrane 11 is placed between the first atomization tube 2 and the second atomization tube 3, namely, the filter membrane is positioned in the slot 31, and the second atomization tube 3 can be made of transparent materials, so that a worker can conveniently observe whether the filter membrane 11 reaches the bottom of the slot 31, and the filter membrane 11 is convenient to install.

The implementation principle of the embodiment 1 is as follows: the breathing simulator 1 simulates the breathing state of a human body, and the atomizer 12 realizes atomization of inhalation preparation samples to generate aerosol so as to simulate the actual scene of the inhalation preparation taken by the human body, and the filter membrane 11 is used for simulating the lung of the human body and filtering the inhalation preparation. The inhalation formulation in the filter membrane 11 is extracted through the subsequent processes of rinsing, soaking, squeezing, spin-drying, etc., so that the total delivery amount and the delivery rate of the inhalation formulation can be accurately tested.

Example 2:

referring to fig. 3, it is different from embodiment 1 in that: in order to reduce the condensation phenomenon of the atomized sample in the first atomization tube 2 and the second atomization tube 3, a temperature sensing element 21 for detecting the temperature in the tube is arranged in the first atomization tube 2, the temperature sensing element 21 can adopt DS18B20, the temperature sensing element 21 is connected with a controller, the controller can adopt a single chip microcomputer, and temperature control elements are arranged outside the first atomization tube 2 and the second atomization tube 3. The controller is used for acquiring the temperature in the pipe through the temperature sensing element 21 and operating according to the temperature control and control element of the temperature in the pipe so as to enable the temperature in the pipe to be lower than the temperature outside the pipe. In other embodiments, the temperature sensing element 21 may be disposed within the atomizing cup 13.

The 3 overcoat of second atomizing pipe is equipped with filling tube 5, and when first atomizing pipe 2 inserted in slot 31, filling tube 5 cup jointed on first atomizing pipe 2, and the both ends opening of filling tube 5 is equipped with the sealing washer, and filling tube 5 passes through sealing washer and first atomizing pipe 2, 3 sealing connection of second atomizing pipe. The temperature control component can adopt a water bath tank with adjustable temperature, for example, a high-low temperature circulating water tank of HWY-10 type, which is communicated with the interlayer space between the filling pipe 5 and the first atomizing pipe 2 and the second atomizing pipe 3.

The implementation principle of the embodiment 2 is as follows: the controller obtains the interior temperature of pipe of first atomizing pipe 2, if the intraductal temperature is higher than the outside of tubes temperature, then start temperature control spare, control temperature control spare to fill into the filling pipe 5 temperature and the intraductal temperature unanimous, or be higher than the liquid or the gas of intraductal temperature, thereby avoid the interior heat of external cooling to make the condensation of atomizing medicine composition on the inside pipe wall, thereby avoid delivering the total volume and appearing reducing, and then reduce the precision influence to delivering efficiency measurement, can reduce the pollution of first atomizing pipe 2 and 3 inside pipe walls of second atomizing pipe simultaneously, reduce the frequency of clearance maintenance, conveniently carry out the repetition test.

Example 3:

referring to fig. 4, it is different from embodiment 2 in that: a plurality of through-holes 51, a plurality of through-holes 51 evenly distributed have all been seted up on first atomizing pipe 2 and the second atomizing pipe 3. And a nitrogen generator is connected to the filling pipe 5, the nitrogen generator replaces a temperature control member, which can generate pure nitrogen, and in other embodiments, the nitrogen generator can be replaced with an air filter to absorb external air and generate pure dust-free air. And the inside and outside of the first atomization tube 2 are all provided with air pressure sensors, the air pressure sensors are connected with a processor, the air pressure sensors are used for detecting the air pressure inside and outside the first atomization tube 2, when the air pressure inside the first atomization tube 2 is higher than the air pressure outside the first atomization tube, the nitrogen output of the nitrogen generator is promoted, or the opening degree of a preset electromagnetic valve between the nitrogen generator and the filling tube 5 is adjusted, so that the air pressure outside the first atomization tube 2 is consistent with the air pressure inside the first atomization tube 2, and the aerosol of the sample is prevented from leaking.

The implementation principle of the embodiment 3 is as follows: when the breathing simulator 1 simulates an inspiration state, negative pressure is generated in the first atomizing pipe 2 and the second atomizing pipe 3, on one hand, aerosol generated by an atomized sample is extracted to enable the aerosol to penetrate through the filter membrane 11, on the other hand, nitrogen in the filling pipe 5 enters the first atomizing pipe 2 and the second atomizing pipe 3 through the through hole 51, and the flux of the nitrogen is lower than that of the atomized sample. The entered nitrogen forms a nitrogen layer on the inner walls of the tubes of the first atomization tube 2 and the second atomization tube 3, and the aerosol of the sample is difficult to contact with the inner walls of the tubes due to the existence of the nitrogen layer when passing through the first atomization tube 2 and the second atomization tube 3, so that the loss of the aerosol adhered on the inner walls of the tubes is reduced, on one hand, the measurement error caused by the adhesion of the aerosol can be reduced, and the measurement accuracy of the total delivery amount and the delivery rate is improved; on the other hand, the pollution to the inner walls of the first atomizing pipe 2 and the second atomizing pipe 3 can be reduced, the frequency of cleaning and maintenance is reduced, and repeated tests are convenient to perform.

Example 4:

referring to fig. 5 and 6, the difference from embodiment 1 is that: the integrative first stationary blade 22 that is provided with on the first atomizing pipe 2, first stationary blade 22 is the ring form and with first atomizing pipe 2 coaxial distribution, an organic whole is provided with second stationary blade 33 on the second atomizing pipe 3, second stationary blade 33 is the ring form and with second atomizing pipe 3 coaxial distribution, wear to be equipped with double-screw bolt 23 on the first stationary blade 22, the screw has been seted up on the second stationary blade 33, double-screw bolt 23 and screw threaded connection, and the axial of double-screw bolt 23 is unanimous with the direction that first atomizing pipe 2 inserted slot 31.

The film outlet has been seted up to the lateral wall of second atomizing pipe 3, set up the sliding channel 32 with the film outlet intercommunication in the second atomizing pipe 3, sliding channel 32 radially distributes along second atomizing pipe 3, it is provided with support 4 to slide along the radial of second atomizing pipe 3 in the sliding channel 32, support 4 includes solid fixed ring 41 and support ring 42, wherein solid fixed ring 41 is on a parallel with the radial cross-section of second atomizing pipe 3, elastic connection portion 43 is connected to the bottom of solid fixed ring 41, elastic connection portion 43 is connected with support ring 42, elastic connection portion 43 is used for increasing the contained angle of solid fixed ring 41 and support ring 42.

The fixing ring 41 and the support ring 42 are both annular, an annular groove 411 is coaxially formed in the fixing ring 41, the annular groove 411 is used for placing the filter membrane 11, and when the support ring 42 rotates to be close to the fixing ring 41, the edge of the filter membrane 11 is clamped by the fixing ring 41. The sliding channel 32 is communicated with the slot 31, the support ring 42 faces the slot 31 when the bracket 4 is inserted into the sliding channel 32, and the first nebulizing tube 2 abuts against the support ring 42 when inserted into the slot 31, at this time, the filter membrane 11 covers the opening of the first nebulizing tube 2, and the aerosol of the sample passes through the support ring 42 and the filter membrane 11.

The outer wall of the second atomization tube 3 is integrally provided with a guide post 6, the peripheral wall of the fixing ring 41 is provided with a slide block 61, and the slide block 61 is slidably sleeved on the guide post 6. The guide post 6 is sleeved with an elastic member 62, the elastic member 62 is a spring, one end of the elastic member 62 is fixedly bonded with the bottom of the guide post 6, and the top of the elastic member 62 is used for contacting with the sliding block 61. Two groups of sliding blocks 61, elastic pieces 62 and guide columns 6 are arranged and symmetrically distributed along the central axis of the second atomizing pipe 3. In order to prevent the slider 61 from coming off the guide post 6, a nut 63 is screwed to the tip of the guide post 6, and the stroke of the slider 61 is limited by the nut 63.

The implementation principle of the embodiment 4 is as follows: before the experiment, the filter membrane 11 is placed in the annular groove 411 of the fixing ring 41, then the fixing ring 41 is pushed into the sliding channel 32, the edge of the membrane outlet extrudes the support ring 42, and the support ring 42 is matched with the fixing ring 41 to press the edge of the filter membrane 11. When the bracket 4 completely enters the sliding channel 32, the first atomizing pipe 2 is pushed to tightly abut against the supporting ring 42 and the stud 23 is locked, so that the bracket 4 is prevented from being ejected, and the installation of the filter membrane 11 is completed.

After the experiment, loosen double-screw bolt 23, first atomizing pipe 2 is not hard up this moment, and support 4 pops out under the effect of elastic component 62, and support ring 42 rotates under the effect of elastic connecting portion 43 simultaneously and exposes filter membrane 11, and the staff can take out filter membrane 11 at this moment and carry out the follow-up processes of extracting the sample such as drip washing, also can directly drip washing together with support 4 simultaneously, avoids sample composition on the filter membrane 11 to adhere on slot 31 inner wall and be difficult to extract to this further reduces measuring error, promotes measurement accuracy. And because first atomizing pipe 2 need not to separate with second atomizing pipe 3 to this work load that reduces loading and unloading improves experimental efficiency.

The above embodiments are preferred embodiments of the present application, and the protection scope of the present application is not limited by the above embodiments, so: all equivalent changes made according to the structure, shape and principle of the present application shall be covered by the protection scope of the present application.

Claims (10)

1. A sample testing method for inhalation formulation delivery rate and total delivered amount characterized by: the method comprises the following steps:

arranging a filter membrane (11) at a test port of the breathing simulator (1);

connecting the breathing simulator (1) and the atomizer (12);

taking a quantitative sample of the inhaled formulation and placing it in a container communicating with an atomizer (12);

starting the breathing simulator (1) and the atomizer (12) for setting time to ensure that the sample is atomized first and then passes through the filter membrane (11);

taking down the filter membrane (11), taking the cleaning solvent, and carrying out quantitative leaching on the filter membrane (11) to obtain leacheate;

centrifuging the filter membrane (11) to obtain a centrifugate;

taking the centrifugal liquid, and mixing the centrifugal liquid with the obtained leacheate to obtain a mixed liquid;

diluting the mixed solution to a constant volume to obtain a test solution;

measuring measurement data corresponding to the amount of the inhaled formulation sample in the test solution;

the rate of delivery and the total amount delivered of the sample are calculated from the measurement data obtained.

2. Sample test method of inhalation formulation delivery rate and total delivered amount according to claim 1 characterized by: after the step of taking the cleaning solvent and carrying out quantitative leaching on the filter membrane (11), the method also comprises the following steps:

soaking the filter membrane (11) by using a soaking solvent to obtain a soaking solution;

extruding the filter membrane (11) to obtain an extrusion liquid;

mixing the obtained soaking solution and the obtained extrusion solution into the mixed solution;

diluting the mixed solution to a constant volume to obtain the test solution.

3. Sample test method of inhalation formulation delivery rate and total delivered amount according to claim 1 characterized by: the centrifugation treatment comprises:

putting the filter membrane (11) into a centrifuge tube, putting the centrifuge tube into a centrifuge, and setting the centrifugation rate and time parameters;

and taking the liquid in the centrifugal tube, and mixing the liquid with the obtained leacheate to obtain a mixed solution.

4. A sample test method of inhalation formulation delivery rate and total delivered amount according to claim 3, characterized in that: the centrifuging tube includes the collecting tube and is used for placing the chimney filter of filter membrane (11), the collecting tube cup joints outside the chimney filter, it has the filtration pore to distribute on the chimney filter, the degree of depth of collecting tube is greater than the chimney filter.

5. A test device for implementing the sample test method for inhalation formulation delivery rate and total delivered amount of claim 1, characterized by: including atomizer (12), breathing simulator (1), first atomizing pipe (2) and second atomizing pipe (3), atomizer (12), first atomizing pipe (2), second atomizing pipe (3) and breathing simulator (1) communicate in proper order, place in between first atomizing pipe (2) and second atomizing pipe (3) filter membrane (11), first atomizing pipe (2) can be dismantled with second atomizing pipe (3) and be connected.

6. The test device of claim 5, wherein: be connected with first stationary blade (22) on first atomizing pipe (2), be connected with second stationary blade (33) on second atomizing pipe (3), slot (31) have been seted up on second atomizing pipe (3), first atomizing pipe (2) is pegged graft with slot (31) and is cooperated, first stationary blade (22) is fixed and first atomizing pipe (2) is fixed with second atomizing pipe (3) when both are fixed through the screw with second stationary blade (33).

7. The test device of claim 6, wherein: a film outlet is formed in the side wall of the second atomizing pipe (3), a sliding channel (32) communicated with the film outlet is formed in the second atomizing pipe (3), a support (4) is arranged in the sliding channel (32) in a sliding mode along the radial direction of the second atomizing pipe (3), and the support (4) is used for placing a filter membrane (11);

the sliding channel (32) is communicated with the slot (31), the first atomizing pipe (2) abuts against the support (4) when being inserted into the slot (31), and the filter membrane (11) covers the opening of the first atomizing pipe (2).

8. The test device of claim 7, wherein: an elastic part (62) is arranged on the second atomizing pipe (3), one end of the elastic part (62) is connected with the second atomizing pipe (3), and the other end of the elastic part is connected with the support (4);

the screw is including wearing to locate double-screw bolt (23) on first stationary blade (22), the axial of double-screw bolt (23) with the direction that first atomizing pipe (2) inserted slot (31) is unanimous, double-screw bolt (23) and second stationary blade (33) threaded connection.

9. The test device of claim 8, wherein: the holder (4) comprises a fixing ring (41) and a support ring (42), the fixing ring (41) being parallel to the radial section of the second nebulization tube (3);

be connected with elasticity connecting portion (43) between solid fixed ring (41) and support ring (42), elasticity connecting portion (43) are used for the contained angle of solid fixed ring (41) of increase and support ring (42), just place on solid fixed ring (41) filter membrane (11), work as support ring (42) rotate and are close to the edge that solid fixed ring (41) pressed from both sides tight filter membrane (11) when solid fixed ring (41).

10. The test device of claim 5, wherein: a temperature sensing element (21) for detecting the air temperature in the pipe is arranged in the first atomizing pipe (2), the temperature sensing element (21) is connected with a controller, and a temperature control part is arranged outside the first atomizing pipe (2) and/or the second atomizing pipe (3);

the controller is used for acquiring the air temperature in the pipe and controlling the temperature control piece to operate according to the air temperature in the pipe so as to enable the air temperature in the pipe to be always lower than or equal to the air temperature outside the pipe.

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