CN111284917A - Actuator for aerosol administration and aerosol administration system containing the same - Google Patents

Abstract

The invention discloses a driver for aerosol administration and an aerosol administration system containing the same. The driver includes two or more vertically arranged drug delivery tubes, each of which is enclosed to form a drug delivery channel; the driver also includes a confluence portion and a vertically arranged drug mixing tube, and the drug mixing tubes are enclosed to form a drug delivery channel. The drug mixing channel; the confluence part and each drug delivery pipe are located on the same side of the entrance of the drug mixing channel; each platform part is communicated with the confluence part; the confluence part is communicated with the drug mixing channel; the side wall of the drug mixing channel is also provided with There are spray holes, the diameter of the spray hole is 0.25-0.6 mm, and the depth of the spray hole is 0.4-1.0 mm; the distance between the center of the spray hole and the top of the medicine mixing tube is 3.0-7.0 mm. The driver and the aerosol drug delivery system can realize the delivery of more than two kinds of drugs, and can make the drugs achieve an ideal dispersion effect.

Description

Actuator for aerosol administration and aerosol administration system containing the same

technical field

The present invention relates to a driver for aerosol administration and an aerosol administration system containing the same.

Background technique

Aerosol means that the medicine, emulsion or suspension is encapsulated in a pressure-resistant container with a special valve system together with a suitable propellant. Preparations that are inhaled in the lungs or sprayed directly to the mucous membranes, skin and spaces of the cavity for disinfection. Aerosol cans, valves and valve stems together constitute an aerosol delivery system. The general application of metered dose inhalation aerosol is to fill an aerosol can in a drive, and then realize the delivery process of the drug by pressing.

However, aerosols containing more than two APIs are often used. One method is to prepare compound aerosols, that is, to put more than two APIs into a tank for administration. This method is very useful for drugs. There are certain requirements for research and stability; an alternative is to administer two or more aerosols containing a single API at the same time.

At present, there is only a driver suitable for one aerosol can in the prior art, and no driver suitable for two or more aerosol cans, so that the simultaneous administration of multiple products cannot be realized.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a new type of aerosol due to the lack of a driver suitable for two or more aerosol cans in the prior art, and thus the simultaneous administration of multiple products cannot be realized. Actuator for aerosol drug delivery and aerosol drug delivery system containing the same. The driver for aerosol administration can insert two or more aerosol delivery systems into it, thereby realizing the delivery of two or more drugs, and can make the drugs achieve an ideal dispersion effect. The aerosol drug delivery system can realize the delivery of two or more drugs, and can make the drugs achieve an ideal dispersion effect.

The present invention solves the above-mentioned technical problems through the following technical solutions:

The present invention provides a driver for aerosol administration, the driver comprises two or more vertically arranged drug delivery tubes, each of the drug delivery tubes is enclosed to form a drug delivery channel, and each of the drug delivery tubes The inside of the delivery channel is divided into an interface part and a platform part in turn along the drug delivery direction, each of the interface parts is used to cooperate with the valve stem of the corresponding aerosol delivery system, and each of the platform parts is used to When the valve stem of the aerosol delivery system is pressed, the valve stem of the aerosol delivery system ejects the drug along the drug delivery direction and restricts the movement of the valve stem of the aerosol delivery system along the drug delivery direction; so The driver also includes a confluence part and a vertically arranged medicine mixing pipe, the medicine mixing pipe is enclosed to form a medicine mixing channel; the converging part and each of the medicine delivery pipes are located at the entrance of the medicine mixing passage Each of the platform parts is communicated with the confluence part; the confluence part is communicated with the drug mixing channel; the side wall of the drug mixing channel is also provided with a spray hole, and the spray hole is used for For spraying the medicine, the diameter of the spray hole is 0.25-0.6 mm, the depth of the spray hole is 0.4-1.0 mm; the distance between the center of the spray hole and the top of the medicine mixing pipe is 3.0-7.0 mm mm.

In the above driver, preferably, the number of the drug delivery tubes is two.

In the above-mentioned driver, preferably, each of the drug delivery tubes is arranged in the same manner, and each of the platform portions is located at the same height in the drug delivery tube.

In the above driver, preferably, the interface portion is a vertical cylindrical channel. More preferably, the distance between the axes of two adjacent interface parts is 18-22 mm, and further preferably, the distance between the axes of two adjacent interface parts is 18-20 mm.

In the above driver, preferably, the inner diameter of the interface portion is equal to the outer diameter of the valve stem of the aerosol delivery system, and generally there is a machining tolerance of 1%-5%.

In the above driver, preferably, the platform portion is a vertical cylindrical channel.

In the above driver, preferably, the inner diameter of the platform portion is ±0.6 mm of the inner diameter of the valve stem of the aerosol delivery system.

In the above driver, preferably, the platform portion and the confluence portion are communicated with each other through a transition portion, and the transition portion is a circular arc pipe section that enables a smooth transition between the platform portion and the confluence portion. More preferably, the inner diameter of the transition portion is equal to the inner diameter of the interface portion.

In the above driver, preferably, the inner diameter of the medicine mixing tube is 2.5-3.3 mm, more preferably 2.8-3.2 mm.

In the above driver, preferably, the outer diameter of the medicine mixing tube is 3.5 mm.

In the above driver, preferably, the medicine mixing channel is a vertical cylindrical channel.

In the above driver, the depth of the spray hole refers to the depth of the spray hole in the direction perpendicular to the medicine mixing tube. The diameter of the spray holes is preferably 0.25-0.55 mm. The depth of the spray holes is preferably 0.45-1.0 mm. The distance between the center of the spray hole and the top of the medicine mixing tube is preferably 3.5-6.0 mm.

The number of the spray holes is preferably one.

In the above driver, preferably, the material of the driver is plastic, more preferably PET material, PBT material, PE material or PP material. For example, the actuator can be produced by one-time molding through mold processing.

In the above driver, the height of the driver is preferably 40-80 mm.

In the above driver, the driver further has a casing, which can fix the drug delivery tube without affecting the spray hole to spray the drug.

The present invention also provides an aerosol drug delivery system, the aerosol drug delivery system comprising the aforementioned driver for aerosol drug delivery and two or more aerosol drug delivery systems, each of the aerosol drug delivery systems The valve stem of the delivery system is matched with one of the interface parts; the inner diameter of the valve stem of the aerosol delivery system is 2.5-3.3 mm.

In the above-mentioned aerosol delivery system, the aerosol delivery system generally includes a valve stem, a valve and a tank containing an aerosol; the valve of the aerosol delivery system and the tank of the aerosol delivery system After filling the medicine, the body is sealed by the sealing device, and the sealing is realized by the rubber gasket.

In the above aerosol delivery system, preferably, the inner diameter of the valve stem of the aerosol delivery system is 2.8-3.2 mm, for example, 3.16 mm.

In the above aerosol delivery system, preferably, the outer diameter of the valve stem of the aerosol delivery system is 3.5 mm.

In the above aerosol delivery system, preferably, the distance between the axes of the valve stems of two adjacent aerosol delivery systems is 18-22 mm.

In the above-mentioned aerosol delivery system, preferably, the outer diameter of the valve of the aerosol delivery system is 14-16 mm.

In the above-mentioned aerosol delivery system, preferably, the valve of the aerosol delivery system contains a spring component, and the spring component is used to restore the tank body of the aerosol delivery system to the In the equilibrium position, the expansion and contraction amount of the spring assembly is 0.6-1.2 mm.

In the above-mentioned aerosol delivery system, preferably, the outer diameter of the tank of the aerosol delivery system is 14-16 mm.

In the above-mentioned aerosol delivery system, preferably, the bottoms of the tanks of each of the aerosol delivery systems are at the same height.

In the above-mentioned aerosol drug delivery system, preferably, the aerosol drug delivery system is further provided with a cap, and the cap is provided with a recess that matches with the bottom of the tank of the aerosol delivery system. The cap can simultaneously move the canister of the aerosol delivery system downward in a vertical direction. In the above technical solution, the design of the groove can fix the can body, and during the pressing process, it can be ensured that the two can bodies are pressed simultaneously.

In the above-mentioned aerosol delivery system, preferably, the aerosols in at least one tank of the aerosol delivery system are beta agonists and at least one tank of the aerosol delivery system. The aerosol is an inhaled glucocorticoid, or, the aerosol in at least one of the canisters of the aerosol delivery system is a beta agonist and the aerosol in at least one canister of the aerosol delivery system. The aerosol is an anticholinergic inhibitor; more preferably, the aerosol in at least one canister of the aerosol delivery system is a beta agonist, and the canister of at least one of the aerosol delivery systems The aerosol in the body is an inhaled glucocorticoid and the aerosol in the canister of at least one of the aerosol delivery systems is an anticholinergic inhibitor.

Wherein, the beta receptor agonist may be a long-acting beta receptor agonist or a short-acting beta receptor agonist, and the long-acting beta receptor agonist refers to a beta receptor whose action duration is 11-12 hours Agonist, the short-acting β-receptor agonist refers to a β-receptor agonist whose action duration is 4-6 hours, preferably salmeterol aerosol, formoterol aerosol, vilan Terrol Aerosol Aerosol, Salbutamol Aerosol or Levosalbutamol Aerosol, more preferably short-acting salbutamol sulfate aerosol or long-acting salmeterol aerosol.

Wherein, the inhaled glucocorticoid is preferably fluticasone aerosol or budesonide aerosol, more preferably fluticasone propionate aerosol.

Wherein, the anticholinergic inhibitor is preferably ipratropium bromide aerosol, tiotropium bromide aerosol or glycopyrronium bromide aerosol.

In a preferred embodiment of the above-mentioned aerosol drug delivery system, the combination of the beta receptor agonist and the inhaled glucocorticoid is as follows: a combination of a long-acting salmeterol aerosol and a fluticasone aerosol , or a combination of a long-acting formoterol aerosol and a budesonide aerosol, or a combination of a long-acting vilanterol aerosol and a fluticasone aerosol.

In a preferred embodiment of the above aerosol delivery system, the combination of the beta receptor agonist and the inhaled glucocorticoid is as follows: a combination of a short-acting salbutamol sulfate aerosol and a budesonide aerosol Combination, alternatively, a combination of long-acting salmeterol aerosol and fluticasone propionate aerosol.

In a preferred embodiment of the above aerosol delivery system, the combination of the beta receptor agonist and the anticholinergic inhibitor is as follows: short-acting albuterol aerosol and ipratropium bromide aerosol Combination of aerosols, or, a combination of a short-acting levalbuterol aerosol and a tiotropium bromide aerosol, or a combination of a long-acting formoterol aerosol and a glycopyrrolate aerosol, or, a long-acting aerosol Combination of vilanterol aerosol and umeclidinium bromide aerosol.

In a preferred embodiment of the above aerosol delivery system, the combination of the beta receptor agonist, the inhaled glucocorticoid and the anticholinergic inhibitor is as follows: long-acting vilanterol Combination of aerosol, umeclidinium aerosol, and budesonide aerosol.

In the above preferred embodiment, the definitions of the long-acting salmeterol aerosol, the long-acting formoterol aerosol and the long-acting vilanterol aerosol are the same as those of the long-acting beta Definitions of receptor agonists; the short-acting salbutamol aerosol, the short-acting levalbuterol aerosol, and the short-acting salbutamol sulfate aerosol have the same definitions as the short-acting beta agonists.

The positive improvement effect of the present invention is that: the driver for aerosol administration can insert two or more aerosol delivery systems into it, thereby realizing the delivery of two or more drugs, and enabling the drugs to achieve ideal dispersion Effect. The aerosol drug delivery system can realize the delivery of two or more drugs, and can make the drugs achieve an ideal dispersion effect.

Description of drawings

1 is a cross-sectional view of the vertical plane where the axis of the drug delivery channel and the axis of the drug mixing channel of the driver according to Embodiments 1-5 of the present invention are located;

2 is a cross-sectional view of the vertical plane where the axis of the spray hole of the driver according to Embodiment 1-5 of the present invention is located;

3 is a cross-sectional view of the drug delivery system according to Embodiments 1-5 of the present invention along a vertical plane where the axis of the drug delivery channel of the driver and the axis of the drug mixing channel are located.

Description of reference numbers:

drug delivery tube 10

Interface 11

Platform Department 12

Transition 20

Medication Mixing Tube 30

Drug Mixing Channel 31

spray hole 32

spray hole depth h

Aerosol Delivery Systems 40

Confluence 50

Detailed ways

The present invention is further described below by way of examples, but the present invention is not limited to the scope of the described examples. The experimental methods that do not specify specific conditions in the following examples are selected according to conventional methods and conditions, or according to the product description.

In the following examples, salbutamol sulfate aerosols (200 per bottle, each containing 100 micrograms of salbutamol sulfate) and budesonide aerosols (100 per bottle, each containing budesonide 200 micrograms) are Shanghai Shanghai Pharmaceuticals. The commercially available products of Xinyi Pharmaceutical Co., Ltd., and the aerosols of fluticasone propionate and salmeterol are commercially available products of GlaxoSmithKline Pharmaceuticals Co., Ltd.

In the following examples, long-acting beta-receptor agonists refer to beta-receptor agonists whose action duration is 11-12 hours, and short-acting beta-receptor agonists refer to beta-receptor agonists whose action duration is 4-6 hours. body agonist.

Examples 1-5

(1) Actuator for aerosol administration

As shown in FIG. 1 and FIG. 2, the driver for aerosol administration includes two or more vertically arranged drug delivery tubes 10. Each drug delivery tube 10 is enclosed to form a drug delivery channel. The delivery channel is divided into an interface part 11 and a platform part 12 in turn along the drug delivery direction, each interface part 11 is used to cooperate with the valve stem of the corresponding aerosol delivery system, and each platform part 12 is used to When the valve stem of the aerosol delivery system is pressed, the valve stem of the aerosol delivery system ejects the drug along the drug delivery direction and restricts the movement of the valve stem of the aerosol delivery system along the drug delivery direction; the driver further comprises a confluence portion 50 and a vertically arranged medicine mixing pipe 30, the medicine mixing pipe 30 encloses the medicine mixing channel 31; Both are communicated with the confluence part 50; the confluence part 50 is communicated with the medicine mixing channel 31; the side wall of the medicine mixing channel 31 is also provided with a spray hole 32, and the spray hole 32 is used for spraying the medicine.

Among them, the number of drug delivery tubes 10 is two.

Wherein, each drug delivery tube 10 is arranged in the same manner, and each platform portion 12 is located at the same height in the drug delivery tube 10 .

Wherein, the interface portion 11 is a vertical cylindrical channel.

Wherein, the inner diameter of the interface portion 11 is equal to the outer diameter of the valve stem of the aerosol delivery system, and generally there is a machining tolerance of 1%-5%.

The platform portion 12 is a vertical cylindrical channel.

Wherein, the inner diameter of the platform portion 12 is ±0.6 mm of the inner diameter of the valve stem of the aerosol delivery system.

The platform part and the junction part 50 communicate with each other through the transition part. The transition part 20 is a circular arc pipe section that can make the platform part 12 and the junction part 50 smoothly transition; the inner diameter of the transition part 20 is equal to that of the interface part 11 .

The outer diameter of the medicine mixing tube 30 is 3.5 mm.

Wherein, the medicine mixing channel 31 is a vertical cylindrical channel.

The depth h of the spray hole refers to the depth of the spray hole 32 in the direction perpendicular to the medicine mixing tube 30 (as shown in FIG. 2 ); the number of spray holes 32 is one.

Wherein, the material of the driver is plastic, such as PET material, PBT material, PE material or PP material.

Wherein, the driver also has a casing, and the casing can fix the drug delivery tube 10 without affecting the spray hole 32 to spray the drug.

(2) Aerosol drug delivery system

The aerosol drug delivery system shown in FIG. 3, the aerosol drug delivery system includes the driver shown in FIG. 1 and FIG. 2 and two or more aerosol drug delivery systems 40 for the above-mentioned aerosol drug delivery, The valve stem of each aerosol delivery system 40 cooperates with a port 11 .

Wherein, the aerosol delivery system 40 generally includes a valve stem, a valve and a tank containing aerosol; the valve of the aerosol delivery system 40 and the tank of the aerosol delivery system 40 pass through a sealing device after filling the drug Grab seal, sealed with rubber gasket.

The outer diameter of the valve stem of the aerosol delivery system 40 is 3.5 mm.

Wherein, the outer diameter of the valve of the aerosol delivery system 40 is 14-16 mm.

Wherein, the valve of the aerosol delivery system 40 contains a spring assembly, the spring assembly is used to restore the tank body of the aerosol delivery system 40 to the equilibrium position after pressing, and the expansion and contraction amount of the spring assembly is 0.6-1.2 mm.

Wherein, the outer diameter of the tank of the aerosol delivery system 40 is 14-16 mm.

Therein, the bottoms of the tanks of each aerosol delivery system 40 are at the same height.

Wherein, the aerosol drug delivery system is further provided with a cap, and the cap is provided with a groove matched with the bottom of the tank of the aerosol delivery system 40 , and the cap can simultaneously displace the tank of the aerosol delivery system 40 Move vertically downwards. In the above technical solution, the design of the groove can fix the can body, and in the process of pressing, it can ensure that the two can bodies are pressed at the same time.

Among them, the relevant structural parameters of the driver for aerosol administration and the aerosol administration system are shown in the following table.

The types and combinations of the aerosols in the aerosol delivery system 40 in Examples 1-5 correspond to the contents of the relevant tables in Examples 1-5 respectively.

Effect Example 1-2 Combination of short-acting salbutamol sulfate aerosol and budesonide aerosol

Among them, salbutamol sulfate aerosol specifications: 100 micrograms/press; budesonide aerosol: 200 micrograms/press, 100 micrograms/press. The HPLC assay results of the drug delivery system containing the aerosol delivery system 40 of the following combinations are as follows:

Effect Example 3-5 Combination of fluticasone propionate aerosol and long-acting salmeterol aerosol

Among them, fluticasone propionate aerosol specifications: 50 micrograms/press, 125 micrograms/press, 250 micrograms/press; salmeterol aerosol: 25 micrograms/press. The HPLC assay results of the drug delivery system containing the aerosol delivery system 40 of the following combinations are as follows:

Although the specific embodiments of the present invention are described above, those skilled in the art should understand that this is only an illustration, and the protection scope of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principle and essence of the present invention, but these changes and modifications all fall within the protection scope of the present invention.

Claims (10)

1. A driver for aerosol administration, characterized in that, the driver comprises two or more vertically arranged drug delivery tubes, each of which is enclosed to form a drug delivery channel, and each The drug delivery channel is divided into an interface part and a platform part in turn along the drug delivery direction, each of the interface parts is used to cooperate with the valve stem of the corresponding aerosol delivery system, and each of the platform parts is for causing the valve stem of the aerosol delivery system to eject the drug in the drug delivery direction and restricting the valve stem of the aerosol delivery system in the drug delivery direction when the valve stem of the aerosol delivery system is pressed The driver also includes a confluence part and a vertically arranged medicine mixing pipe, the medicine mixing pipe is enclosed to form a medicine mixing channel; the converging part and each of the medicine delivery pipes are located in the medicine mixing pipe The same side of the entrance of the channel; each of the platform parts is communicated with the confluence part; the confluence part is communicated with the drug mixing channel; the side wall of the drug mixing channel is also provided with a spray hole, the The spray hole is used to spray the medicine, the diameter of the spray hole is 0.25-0.6 mm, and the depth of the spray hole is 0.4-1.0 mm; the distance between the center of the spray hole and the top of the medicine mixing pipe is 3.0-7.0mm. 2. The driver for aerosol administration according to claim 1, wherein the number of the drug delivery tubes is 2; And/or, each of the drug delivery tubes is arranged in the same manner, and each of the platform portions is located at the same height in the drug delivery tube. 3. The driver for aerosol administration according to claim 1, wherein the interface portion is a vertical cylindrical channel; preferably, between the axes of two adjacent interface portions The distance is 18-22 mm; more preferably, the distance between the axes of two adjacent interface parts is 18-20 mm; and/or, the inner diameter of the interface portion is equal to the outer diameter of the valve stem of the aerosol delivery system; And/or, the platform part is a vertical cylindrical channel; And/or, the inner diameter of the platform portion is ±0.6 mm of the inner diameter of the valve stem of the aerosol delivery system; And/or, the platform portion and the confluence portion are communicated through a transition portion, and the transition portion is a circular arc pipe section that enables a smooth transition between the platform portion and the confluence portion; preferably, the inner diameter of the transition portion is is equal to the inner diameter of the interface portion. 4. The driver for aerosol administration according to claim 1, wherein the inner diameter of the medicine mixing tube is 2.5-3.3 mm, preferably 2.8-3.2 mm; And/or, the outer diameter of the medicine mixing tube is 3.5 mm; And/or, the medicine mixing channel is a vertical cylindrical channel. 5. The driver for aerosol administration according to claim 1, wherein the diameter of the spray hole is 0.25-0.55 mm; And/or, the depth of the spray hole is 0.45-1.0 mm; And/or, the distance between the center of the spray hole and the top of the drug mixing tube is 3.5-6.0 mm; And/or, the number of the spray holes is one. 6. The driver for aerosol administration according to claim 1, wherein the material of the driver is plastic, preferably PET material, PBT material, PE material or PP material; and/or, the height of the driver is 40-80 mm; And/or, the driver further has a housing, which can fix the drug delivery tube without affecting the spray hole to spray the drug. 7. An aerosol drug delivery system, characterized in that the aerosol drug delivery system comprises a driver for aerosol drug delivery as claimed in any one of claims 1-6 and two or more aerosols In the aerosol delivery system, the valve stem of each aerosol delivery system is matched with one of the interface parts; the inner diameter of the valve stem of the aerosol delivery system is 2.5-3.3 mm. 8. The aerosol drug delivery system according to claim 7, wherein the inner diameter of the valve stem of the aerosol drug delivery system is 2.8-3.2 mm; And/or, the outer diameter of the valve stem of the aerosol delivery system is 3.5 mm; And/or, the distance between the axes of the valve stems of two adjacent aerosol delivery systems is 18-22 mm; And/or, the outer diameter of the valve of the aerosol delivery system is 14-16 mm; And/or, the valve of the aerosol delivery system contains a spring assembly, the spring assembly is used to restore the tank body of the aerosol delivery system to the equilibrium position after pressing, and the expansion and contraction of the spring assembly The amount is 0.6-1.2 mm; And/or, the outer diameter of the tank of the aerosol delivery system is 14-16 mm; and/or, the bottoms of the tanks of each of the aerosol delivery systems are at the same height; And/or, the aerosol delivery system is further provided with a cap, the cap is provided with a groove matched with the bottom of the tank of the aerosol delivery system, and the cap can simultaneously The canister of the aerosol delivery system moves downwards in a vertical direction. 9. The aerosol drug delivery system according to claim 7 or 8, wherein, in the aerosol drug delivery system, the aerosol in the tank of at least one of the aerosol drug delivery systems is The beta agonist and the aerosol in the canister of at least one of the aerosol delivery systems are inhaled glucocorticoids, or the aerosol in the canister of at least one of the aerosol delivery systems is beta The receptor agonist and at least one aerosol in the tank of the aerosol delivery system are anticholinergic inhibitors; preferably, in the aerosol delivery system, at least one of the aerosols The aerosol in the canister of the drug delivery system is a beta agonist, the aerosol in the canister of at least one of the aerosol delivery systems is an inhaled glucocorticoid and at least one of the aerosol delivery systems The aerosol in the tank is an anticholinergic inhibitor; Wherein, the beta receptor agonist is preferably a long-acting beta receptor agonist or a short-acting beta receptor agonist, and the long-acting beta receptor agonist refers to a beta receptor whose action duration is 11-12 hours. Receptor agonists, the short-acting beta receptor agonists refer to beta receptor agonists whose action duration is 4-6 hours, more preferably salmeterol aerosol, formoterol aerosol, vilanterol aerosol, albuterol aerosol or levsalbutamol aerosol, further more preferably a short-acting salbutamol sulfate aerosol or a long-acting salmeterol aerosol; the inhaled glucocorticoid Preferably fluticasone aerosol or budesonide aerosol, more preferably fluticasone propionate aerosol; the anticholinergic inhibitor is preferably ipratropium bromide aerosol, tiotropium ammonium bromide aerosol or glycopyrronium bromide aerosol. 10. The aerosol drug delivery system according to claim 9, wherein the combination of the beta receptor agonist and the inhaled glucocorticoid is as follows: long-acting salmeterol aerosol and fluticasone A combination of aerosols, or a combination of a long-acting formoterol aerosol and a budesonide aerosol, or a combination of a long-acting vilanterol aerosol and a fluticasone aerosol; or, the beta The combination of the receptor agonist and the inhaled glucocorticoid is as follows: a combination of a short-acting salbutamol sulfate aerosol and a budesonide aerosol, or a long-acting salmeterol aerosol and a fluticasone propionate aerosol The combination; Alternatively, the combination of the beta agonist and the anticholinergic inhibitor is as follows: a combination of a short-acting salbutamol aerosol and an ipratropium bromide aerosol, or a short-acting levalbuterol aerosol Combination with tiotropium bromide aerosol, or, a combination of long-acting formoterol aerosol and glycopyrronium bromide aerosol, or, a combination of long-acting vilanterol aerosol and umeclidinium bromide aerosol a combination of aerosols; Alternatively, the combination of the beta agonist, the inhaled glucocorticoid and the anticholinergic inhibitor is as follows: long-acting vilanterol aerosol, umeclidinide aerosol and budesonide Combination of aerosols.

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