Use of atomizing cups and atomizing inhalation administration

Abstract

The present invention discloses an atomization cup and its use in atomization inhalation administration, particularly in atomization inhalation administration of drugs for preventing and / or treating respiratory diseases (e.g., SARS-CoV-2 vaccines). The atomization cup, when containing an antistatic agent, can effectively maintain the stability of the drug aerosol over a certain period of time, stabilize the particle size, reduce drug residue in the cup, ensure an effective inhalable dose, facilitate simple and convenient administration, significantly improve vaccination efficiency, and be suitable for large-scale vaccination.

Description

[Technical Field]

[0001] The present invention relates to the art of biopharmaceuticals, and more specifically to atomizing cups and their use in atomizing inhalation administration, in particular to their use in atomizing inhalation administration of drugs for the prevention and / or treatment of respiratory diseases (e.g., SARS-CoV-2 vaccine). [Background technology]

[0002] Currently, one treatment method for respiratory diseases is nebulized inhalation, which uses a nebulizer to disperse medication into fine mist droplets that are inhaled by the patient through their nose or mouth. The nebulized drug acts directly on the target organ, increasing the local concentration of the drug and achieving a therapeutic effect. Nebulized inhalation has a very good therapeutic effect on bronchiolitis, asthmatic bronchitis, bronchial asthma, acute and chronic bronchitis, acute laryngitis, and acute pneumonia.

[0003] Atomized inhalation vaccines are vaccines that provide immunity through atomized inhalation. So-called atomized inhalation immunity is a method in which the vaccine is atomized into fine particles by an atomizer and inhaled through breathing. These fine particles enter the airways and lungs, triggering mucosal immunity.

[0004] Equipment and devices that enable atomized inhalation therapy and immunization are crucial for the implementation and quality of treatment and immunization, and are attracting significant attention from researchers and developers. Conventional atomized administration devices primarily administer drugs by inhaling while atomizing, requiring instruction to subjects before administration. Children, and many adults, often have poor control over the frequency of inhalation administration and self-breathing, which greatly affects the inhalation and absorption of drug mist, making it very disadvantageous for immunization. Furthermore, for immunization, to prevent cross-infection, devices used for inhalation by subjects must be disinfected or disposed of after use. Given the need for large-scale vaccination, there is an urgent need to provide atomized administration devices that can prevent cross-infection while keeping costs down and achieving high efficiency in inhalation administration.

[0005] Furthermore, when performing atomized inhalation using an atomizing cup, the atomized chemical mist tends to liquefy at the cup wall due to static electricity, forming droplets that are not properly inhaled into the human body. Therefore, to prevent residual liquefied chemical mist, it is necessary to add an antistatic agent to the atomizing cup to resist static electricity. However, the amount of antistatic agent used also has a significant impact on the chemical mist. If the amount of antistatic agent is low, a large amount of chemical mist accumulates and the residual amount is high, while if the amount of antistatic agent is high, it may negatively affect the molding and feel of the cup itself, as well as the effective amount of chemical mist after atomization. Therefore, it is urgent to find an appropriate antistatic agent and the optimal amount of antistatic agent to ensure the effectiveness of chemical atomization. [Overview of the project] [Problems that the invention aims to solve]

[0006] To overcome the shortcomings of conventional technology, the present invention provides an atomizing cup and its use, which collects and contains drug mist generated by an atomizer and allows a subject to inhale it, thereby producing therapeutic and immune-boosting effects. [Means for solving the problem]

[0007] In a first aspect of the present invention, an atomizing cup is provided, which includes a cup body and a cup lid, wherein an antistatic agent is added to the cup body.

[0008] Specifically, an antistatic agent is also added to the cup lid.

[0009] Specifically, the antistatic agent may be one or more combinations of anionic antistatic agents (e.g., alkyl sulfonates, alkyl phosphates, copolymer salts of maleic anhydride and other monomers, polyacrylates, polystyrene sulfonates), amphoteric antistatic agents (e.g., amphoteric alkylimidazoline salts, alkyl amino acids), nonionic antistatic agents (e.g., fatty acid polyhydric alcohol esters (e.g., glyceryl fatty acid esters, sorbitan fatty acid esters), polyoxyethylene adducts (e.g., polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene alkylamines, etc.), polymeric antistatic agents (e.g., polyoxyethylene fatty acid ethers, polyoxyethylene alkylphenyl ethers, polyethylene glycol fatty acid esters, polyacrylic acid derivatives), and composite antistatic agents, particularly nonionic antistatic agents and / or polymeric antistatic agents.

[0010] Furthermore, the nonionic antistatic agent is preferably one or more combinations of fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, and glycerin monofatty acid ester; the amphoteric antistatic agent is preferably alkyldicarboxymethylammonium ethyl lactone and / or dodecyldimethyl betaine; and the polymeric antistatic agent is preferably one or more combinations of ethylenediamine ethylene oxide dopylene oxide, poly-4-vinylpyridine type polysoap, octylstyrene, and styrene sulfonic acid copolymer type polysoap.

[0011] Cationic quaternary amine salts have high adhesion to polymer materials and excellent antistatic properties, and are commonly used as antistatic agents in plastics. However, they are irritating to the skin and toxic, and therefore fall outside the scope of this invention.

[0012] In some embodiments of the present invention, an antistatic agent is added to the cup body, and the content of the antistatic agent is 0.03% (w / w) or more, particularly 0.05% or more, for example, 0.03% to 10% (for example, 0.05%, 0.1%, 0.2%, 0.25%, 0.5%, 1%, 1.5%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%), particularly 0.05% to 5%.

[0013] In some embodiments of the present invention, an antistatic agent is added to the cup lid, and the content of the antistatic agent is 0.03% (w / w) or more, particularly 0.05% or more, for example, 0.03% to 10% (for example, 0.05%, 0.1%, 0.2%, 0.25%, 0.5%, 1%, 1.5%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%), particularly 0.05% to 5%.

[0014] In some embodiments of the present invention, an antistatic agent is added to both the cup body and the cup lid.

[0015] Specifically, the addition of the antistatic agent to the cup body and / or the cup lid may be performed by adding the raw material components of the antistatic agent to the manufacturing raw materials or adding an antistatic masterbatch to the manufacturing raw materials, particularly by adding an antistatic masterbatch to the manufacturing raw materials. The antistatic agent and the antistatic masterbatch may use appropriate commercially available products according to the plastic materials of the cup body and / or the cup lid.

[0016] Furthermore, a mist inlet and a suction nozzle are opened in the cup lid.

[0017] Specifically, the mist inlet may be opened at any appropriate position of the cup lid, such as the edge, the center, particularly the edge of the cup lid. A sealing member may be provided at the mist inlet to seal the mist inlet until the atomizing cup is used.

[0018] Specifically, the suction nozzle is provided protruding from the cup lid and communicating with the space inside the cup body, and may be of any shape suitable for the subject to inhale the mist, such as tubular or conical. The inlet end of the suction nozzle may be of any shape suitable for the subject to inhale, such as circular or elliptical. A sealing member may be further provided at the inlet of the suction nozzle to seal the suction nozzle before the atomizing cup is used.

[0019] Specifically, the cup lid should be made of plastic, particularly medical-grade plastic, such as polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), polycarbonate (PC), or polylactic acid (PLA), and may be made of PP or PLA in particular. Specifically, the cup lid should be transparent.

[0020] Specifically, the material of the cup body is plastic, especially medical-grade plastic, such as polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), polycarbonate (PC), and polylactic acid (PLA), and may be PP or PLA in particular. Specifically, the cup body is transparent.

[0021] Specifically, the cup body and the cup lid may be integrally molded, or they may be detachably attached, and may be connected, for example, by screws or clips.

[0022] Specifically, the shape of the cup body may be any appropriate shape, such as a cylindrical shape or an inverted frustoconical shape that tapers from top to bottom.

[0023] Specifically, the side wall of the cup body may be further provided with a handle to make it easier to grip the atomizing cup.

[0024] Specifically, the volume of the atomizing cup may be 300 to 800 ml (for example, 300, 350, 400, 450, 500, 550, 600, 700, 800 ml), and may be particularly 500 ml.

[0025] A second aspect of the present invention provides a method for manufacturing an atomizing cup according to the first aspect, which includes the step of adding an antistatic agent component or an antistatic masterbatch to the raw material for manufacturing the cup body.

[0026] In some embodiments of the present invention, the method further includes the step of adding an antistatic agent component or an antistatic masterbatch to the raw materials for manufacturing cup lids.

[0027] Specifically, the method may further include a molding step, for example, molding by methods such as extrusion, injection molding, pressure molding, or blow molding.

[0028] A third aspect of the present invention provides the use of the atomizing cup described in the first aspect in the manufacture of an atomizing inhalation administration device.

[0029] Specifically, the use is the use of the atomizing cup in the manufacture of a device for atomizing and / or treating a drug for preventing and / or treating respiratory diseases.

[0030] Specifically, the apparatus includes an atomizing cup and an atomizer as described in the first aspect of the present invention, and more specifically, the atomizer may be a suitable atomizer such as an ultrasonic atomizer, a compression atomizer, or a vibrating screen atomizer, in particular a vibrating screen atomizer.

[0031] Specifically, these drugs include vaccines such as pneumococcal vaccines, influenza vaccines, coronavirus vaccines, varicella vaccines, Newcastle disease virus vaccines, measles vaccines, tuberculosis vaccines, and house dust mite allergy vaccines.

[0032] In some embodiments of the present invention, the coronavirus vaccine is a SARS-CoV-2 vaccine.

[0033] Specifically, the SARS-CoV-2 vaccine may be a recombinant adenovirus vector vaccine into which the S protein gene of SARS-CoV-2 is inserted. More specifically, the recombinant adenovirus may contain genes (full-length or partial sequences) of other structural proteins of SARS-CoV-2 (such as M protein, E protein, N protein).

[0034] Specifically, the adenovirus may be a human adenovirus (such as AdHu2 type, AdHu5 type, etc.), an animal adenovirus vector such as a chimpanzee adenovirus vector (such as AdC6 type, AdC7 type, AdC36 type, AdC68 type, etc.). In some embodiments of the present invention, the adenovirus is AdHu5.

[0035] Specifically, the content of the recombinant adenovirus in the recombinant adenovirus vector vaccine is 1×10 10 ~5×10 11 VP / ml (specifically, 2×10 9 、4×10 9 、6×10 9 、8×10 9 、1×10 10 、2×10 10 、4×10 10 、6×10 10 、8×10 10 、1×10 11 、2×10 11 、3×10 11 、4×10 11 、5×10 11 VP / ml).

[0036] Specifically, the unit dosage of the drug is 0.05~0.5 ml (such as 0.05, 0.1, 0.2, 0.3, 0.4, 0.5 ml), particularly 0.05~0.2 ml, 0.1 ml.

[0037] In the fourth aspect of the present invention, there is provided a nebulized inhalation administration device including the nebulizing cup described in the first aspect of the present invention and a nebulizer.

[0038] Specifically, the atomizer may be an appropriate atomizer such as an ultrasonic atomizer, a compression atomizer, or a vibrating screen atomizer, and in particular, a vibrating screen atomizer.

[0039] A fifth aspect of the present invention provides the use of the atomizing cup described in the first aspect in atomizing inhalation administration.

[0040] Specifically, the use is the use of the atomizing cup in the atomizing inhalation administration of drugs for the prevention and / or treatment of respiratory diseases.

[0041] Specifically, in this use, the drug has the corresponding definition described in the third aspect of the present invention.

[0042] A sixth aspect of the present invention provides a method for administering a drug by atomization inhalation to a subject using the atomizing cup described in the first aspect.

[0043] Specifically, the method is an atomized inhalation immunization method, where the drug is a vaccine, such as a streptococcal pneumonia vaccine, influenza vaccine, coronavirus vaccine, varicella vaccine, Newcastle disease virus vaccine, measles vaccine, tuberculosis vaccine, or house dust mite allergy vaccine, and in some embodiments of the present invention, the vaccine is a coronavirus vaccine, particularly a SARS-CoV-2 vaccine.

[0044] Specifically, the SARS-CoV-2 vaccine is a recombinant adenovirus vector vaccine in which the SARS-CoV-2 S protein gene is inserted, and more specifically, the recombinant adenovirus may further contain other structural protein genes (e.g., M protein, E protein, N protein) of SARS-CoV-2 (full length or partial sequence).

[0045] Specifically, the adenovirus may be a human adenovirus (e.g., AdHu2, AdHu5, etc.), an animal adenovirus vector such as a chimpanzee adenovirus vector (e.g., AdC6, AdC7, AdC36, AdC68, etc.), and in some embodiments of the present invention, the adenovirus is AdHu5.

[0046] Specifically, the recombinant adenovirus content in the above recombinant adenovirus vector vaccine is 1 × 10⁻⁶ 9 ~5×10 11 VP / ml (specifically, 2 × 10⁻⁶) 9 , 4×10 9 , 6×10 9 , 8×10 9 , 1 x 10 10 , 2×10 10 , 4×10 10 , 6×10 10 , 8×10 10 , 1 x 10 11 , 2×10 11 , 3 x 10 11 , 4×10 11 , 5×10 11 It is VP / ml.

[0047] Specifically, the unit dose of the above vaccine is 0.05 to 0.5 ml (for example, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5 ml), especially 0.05 to 0.2 ml and 0.1 ml.

[0048] Specifically, the method is: Step (1) atomizing the drug using an atomizer, Step (2) involves collecting the drug mist generated in step (1) using the atomizing cup, The procedure includes (3) the subject inhaling a drug mist through the suction nozzle of the atomizing cup.

[0049] Specifically, step (3) should be performed within 30 seconds (s) after mist collection (for example, 20s, 15s, 10s, 5s), and especially within 10 seconds after mist collection is complete.

[0050] Specifically, the atomizer in step (1) may be an appropriate atomizer such as an ultrasonic atomizer, a compression atomizer, or a vibrating screen atomizer, in particular a vibrating screen atomizer.

[0051] As shown in Figures 1-6, the atomizing cup includes a cup body 1 and a cup lid 2. The cup lid includes an atomizing port 21, a reversal stopper 22, a connection part 23 between the reversal stopper and the cup lid, a suction nozzle 24, a stopper 25, a positioning thread 26, and a pull tab 27. When the pull tab 27 is held by hand and the reversal stopper 22 is opened, the atomizer is connected to the cup via the atomizing port 21, and the mist generated when atomizing the drug solution enters the cup through the atomizing port 21. The subject can receive the inoculation by inhaling the mist through the suction nozzle 24. After the inoculation is complete, the stopper 2-5 is held by hand and the positioning thread 26 is pulled to break it, and then the stopper 25 is placed over the suction nozzle 24 to seal the suction nozzle 24. The reversal stopper 22 is also pushed down to make it flush with the surface of the cup lid and seal the atomizing port 21. Sealing the suction nozzle 24 and atomizing port 21 prevents residual mist in the cup from overflowing into the air, thus protecting the environment from contamination by biological products.

[0052] Furthermore, a suction nozzle 24 is provided on the top of the cup lid 2, near the edge, and the suction nozzle 24 protrudes from the surface of the cup lid 2.

[0053] Furthermore, the cup lid 2 further includes a stopper 25, and an insertion portion 251 is provided at the lower end of the stopper 25, and the outer edge contour of the insertion portion 251 may be the same as the inner wall contour of the suction nozzle 24 so that the stopper 25 can be inserted into the suction nozzle 24 and the suction nozzle 24 can be sealed.

[0054] Furthermore, the plug 25 extends outward such that the positioning portion 252 is perpendicular to the insertion portion 251, and the size of the contour of the positioning portion 252 is larger than the size of the contour of the insertion portion 251.

[0055] Furthermore, the stopper 25 is provided with a handle portion 253 at its upper end, perpendicular to the positioning portion, allowing the stopper 25 to be attached and detached manually.

[0056] Furthermore, the stopper 25 is located on the edge of the cup lid 2 and is fixed to the cup lid 2 by two positioning threads 26.

[0057] Furthermore, on the side of the reversal stopper 22, there is a rectangular pull tab 27 perpendicular to the reversal stopper 22, located near the edge.

[0058] Furthermore, the atomizing port 21 and suction nozzle 24 provided on the top of the cup lid 2 are all located near the edge and on both sides of the central axis, and the suction nozzle 24 on the top of the cup lid 2 is elliptical in shape.

[0059] Specifically, the atomizing cup will be disposable to avoid cross-infection. [Effects of the Invention]

[0060] The atomizing cup according to the present invention can be used for atomizing and / or inhaling drugs to prevent and / or treat respiratory diseases. Atomization therapy is primarily an aerosol inhalation therapy method. So-called aerosols are fine solid or liquid particles suspended in the air. Therefore, atomizing inhalation therapy involves using an atomizing device to disperse the drug into fine mist droplets or particles, suspending them in the air, and inhaling them into the respiratory system and lungs. When mist particles accumulate, their properties are affected. Physical mechanisms that cause mist particle accumulation include impact deposition, gravity deposition, diffusion deposition, electrostatic adsorption deposition, and barrier deposition. In order to eliminate the effect of deposition caused by electrostatic adsorption on mist particles, previous studies have shown that adding a food-grade antistatic agent, such as an edible vegetable oil raw material, to the drug formulation increases the volume of the atomized particles to more than 20 μm, making delivery impossible. When the atomizing cup was treated with a static electricity removal device (such as an ion bar, ion gun, or ion fan) immediately before use, it had some effect on preventing the accumulation of the formulation's atomized particles, but it was not significant.

[0061] In this invention, by adding an antistatic agent to the material of the atomizing cup, the combination of the transparent plastic material and the antistatic agent allows the water droplets themselves to maintain stability, thereby obtaining a suitable atomizing effect. This is thought to be because the principle of antistatic action is to form a conductive layer on the surface of the material, thereby lowering its surface resistivity and quickly releasing any static charge that has already been generated. Adding an antistatic agent directly to a transparent plastic material not only exhibits an antistatic effect, but also has the potential to improve the smoothness of the surface of the plastic material, reducing the accumulation of particles due to friction between the atomized particles and the surface of the plastic material. Since the addition of an antistatic agent is not merely an antistatic or smoothing effect, this invention investigated the specific amount of antistatic agent to use in the atomizing cup, using the amount of mist, the amount of mist that can be inhaled, the residual rate of the chemical solution, and the aerodynamics of the aerosol after atomization as comprehensive indicators. The results showed that the usage needs can be met if the amount of antistatic agent used is 0.03% to 10% (mass percentage), and the overall indicators are better if the amount of antistatic agent used is 0.05% to 5% (mass percentage). Specifically, without the addition of an antistatic agent, the transparent plastic atomizing cup has poor mist transport ability, resulting in a high rate of drug residue and rendering it almost unusable. At a concentration of 0.03%, both the antistatic effect and overall mist inhalation performance are slightly reduced. However, increasing the concentration to 6% or 10% improves antistatic properties in a dose-effect relationship, but the overall mist inhalation performance decreases. This indicates that adding a specific amount of antistatic agent is effective in maintaining the stability of the drug mist for a certain period (e.g., within 20 seconds). The particle size remains stable, drug residue in the cup is minimal, and effective inhalation volume and accumulation rate can be ensured. The atomizing cup's structural design further enhances inhalation performance, and particularly when applied in the vaccine field, it allows for simple and convenient administration, significantly increasing vaccination efficiency and enabling its use in large-scale vaccinations. [Brief explanation of the drawing]

[0062] [Figure 1] The diagram shows a schematic structure of the atomizing cup of the present invention, consisting of a cup body 1 and a cup lid 2. [Figure 2] The diagram shows a schematic structure of the cup lid of the atomizing cup of the present invention. The left diagram is a top view, and the right diagram is a cross-sectional view. The components are the atomizing port 21, the reversal stopper 22, the connection part 23 between the reversal stopper and the cup lid, the suction nozzle 24, the stopper 25, the positioning thread 26, and the pull tab 27. [Figure 3] Figure 2 shows a schematic front view of the plug, which consists of an insertion part 251, a positioning part 252, and a handle part 253. [Figure 4] Figure 2 shows a schematic cross-sectional view of the plug, with the positioning portion 252 and the handle portion 253. [Figure 5] Figure 2 shows a schematic diagram of the lower surface of the plug, with the insertion portion 251 and the positioning portion 252. [Figure 6] This diagram shows a schematic three-dimensional structure of the cup lid of the atomizing cup of the present invention. [Figure 7] This shows the results of detecting the amount of mist that can be inhaled 20 seconds after the mist was contained in atomizing cups made of different materials that had undergone different treatments. [Modes for carrying out the invention]

[0063] Unless otherwise defined, all scientific and technical terms used in this invention have the same meanings as those generally understood by those skilled in the art.

[0064] In the present invention, "subject" means a human being who receives the aforementioned administration method (particularly the atomized inhalation immunization method) of the present invention.

[0065] The various publications, patents, and disclosures of published patent specifications cited herein are incorporated herein by reference in their entirety.

[0066] The technical aspects of the present invention will be described clearly and completely below with reference to examples of the present invention, but it is clear that the examples described are only a selection of examples of the present invention, not all examples. All other examples obtained by those skilled in the art without requiring any creative effort based on the examples of the present invention fall within the scope of the present invention. Example 1: Effect of antistatic agent on mist containment in atomizing cups

[0067] 1. Experimental objective: We will examine the mist containment effect of atomizing cups to which each antistatic agent has been added.

[0068] 2. Experimental Design Atomized drug model: Recombinant COVID-19 vaccine (adenovirus type 5 vector) liquid formulation manufactured by CanSino. Atomization amount: 0.1ml. Antistatic agent A: Fatty acid alcohol polyoxyethylene ester (anionic type antistatic agent) Antistatic agent B: Sodium secondary alkyl sulfonate (anionic type antistatic agent) Antistatic agent C: Polyethylene glycol ester (nonionic antistatic agent) Antistatic agent D: Fatty acid alkanolamide (nonionic antistatic agent) Antistatic agent E: Polyethylene oxide (polymeric antistatic agent) Antistatic agent F: Sodium polystyrene sulfonate (polymeric antistatic agent) Antistatic agent G: Alkyl dicarboxymethylammonium ethyl lactone (amphoteric antistatic agent) Antistatic agent H: Dodecyldimethylbetaine (amphoteric antistatic agent) Atomizing cups processed in various ways: Atomization cup 1: Atomization cup (PP) and cup lid (PP); Atomizing cup 2: Atomizing cup (PP + 0.1% antistatic agent A) and cup lid (PP + 0.1% antistatic agent A); Atomizing cup 3: Atomizing cup (PP + 0.1% antistatic agent B) and cup lid (PP + 0.1% antistatic agent B); Atomizing cup 4: Atomizing cup (PP + 0.1% antistatic agent C) and cup lid (PP + 0.1% antistatic agent C); Atomizing cup 5: Atomizing cup (PP + 0.1% antistatic agent D) and cup lid (PP + 0.1% antistatic agent D) Atomizing cup 6: Atomizing cup (PP + 0.1% antistatic agent E) and cup lid (PP + 0.1% antistatic agent E); Atomizing cup 7: Atomizing cup (PP + 0.1% antistatic agent F) and cup lid (PP + 0.1% antistatic agent F); Atomizing cup 8: Atomizing cup (PP + 0.1% antistatic agent G) and cup lid (PP + 0.1% antistatic agent G); Atomizing cup 9: Atomizing cup (PP + 0.1% antistatic agent H) and cup lid (PP + 0.1% antistatic agent H) Detection / Inhalation Method: Detection occurs 20 seconds after atomization. Number of repetitions per group: 3.

[0069] 3. Detection conditions Detection device: 1 / 10,000 electronic balance;

[0070] 4. Experimental Results and Analysis When 0.1 ml of a recombinant COVID-19 vaccine dilution is atomized using an untreated PP atomizing cup, the mist rapidly condenses on the cup wall, and a very small amount of mist remains in the cup 20 seconds after atomization. Adding 0.1% anionic, nonionic, or polymeric antistatic agent to the atomizing cup improves both the antistatic effect and the amount of mist produced. Amount of residue remaining in the cup body and cup lid after atomization is complete Before the experiment, the weight of the cup body and lid was measured using a 1 / 10,000 electronic balance. After atomization was complete and mist inhalation was finished, the weight was measured again using the 1 / 10,000 electronic balance. Chemical solution residual rate = (weight after atomization - weight before atomization) / weight of atomized chemical solution x 100% The results are shown in the table below.

[0071] TIFF0007843744000001.tif59170

[0072] Results and analysis: When atomization was performed using an atomizing cup that had not undergone any treatment, a large amount of mist remained in the cup. Atomizing cups to which an amphoteric antistatic agent was added showed a clear improvement in mist containment performance, while atomizing cups to which anionic, nonionic, or polymeric antistatic agents were added showed a significant improvement in mist containment performance. Example 2: Effect of different concentrations of antistatic agents on mist retention in the atomizing cup

[0073] 1. Experimental objective: We will examine the effectiveness of mist containment in atomizing cups treated using each method.

[0074] 2. Experimental Design Atomized drug model: Recombinant COVID-19 vaccine (adenovirus type 5 vector) liquid formulation manufactured by CanSino. Atomization amount: 0.1ml. Antistatic agent A: High molecular weight type, polyethylene glycol fatty acid ester Antistatic agent B: Nonionic type, polyoxyethylene sorbitan fatty acid ester Antistatic agent C: Anionic type, cetyl potassium phosphate Antistatic agent D: Amphoteric type, dodecyldimethylbetaine Atomization cups processed by each method: Atomization cup 1: Atomization cup (PP) and cup lid (PP); Atomizing cup 2: Atomizing cup (PLA) and cup lid (PLA); Atomizing cup 3: Atomizing cup (PP) and cup lid (PP), static electricity removal using an ion gun; Atomizing cup 4: Atomizing cup (PLA) and cup lid (PLA), static electricity removal by ion gun; Atomizing cup 5-1: Atomizing cup (PP + 0.03% antistatic agent A) and cup lid (PP + 0.03% antistatic agent A); Atomizing cup 5-2: Atomizing cup (PLA + 0.03% antistatic agent A) and cup lid (PLA + 0.03% antistatic agent A); Atomizing cup 5-3: Atomizing cup (PP + 0.03% antistatic agent B) and cup lid (PP + 0.03% antistatic agent B); Atomizing cup 5-4: Atomizing cup (PLA + 0.03% antistatic agent B) and cup lid (PLA + 0.03% antistatic agent B); Atomizing cup 5-5: Atomizing cup (PP + 0.03% antistatic agent C) and cup lid (PP + 0.03% antistatic agent C); Atomizing cups 5-6: Atomizing cup (PLA + 0.03% antistatic agent C) and cup lid (PLA + 0.03% antistatic agent C); Atomizing cups 5-7: Atomizing cup (PP + 0.03% antistatic agent D) and cup lid (PP + 0.03% antistatic agent D); Atomizing cups 5-8: Atomizing cup (PLA + 0.03% antistatic agent D) and cup lid (PLA + 0.03% antistatic agent D); Atomizing cup 6-1: Atomizing cup (PP + 0.05% antistatic agent A) and cup lid (PP + 0.05% antistatic agent A); Atomizing cup 6-2: Atomizing cup (PLA + 0.05% antistatic agent A) and cup lid (PLA + 0.05% antistatic agent A); Atomizing cup 6-3: Atomizing cup (PP + 0.05% antistatic agent B) and cup lid (PP + 0.05% antistatic agent B); Atomizing cup 6-4: Atomizing cup (PLA + 0.05% antistatic agent B) and cup lid (PLA + 0.05% antistatic agent B); Atomizing cup 6-5: Atomizing cup (PP + 0.05% antistatic agent C) and cup lid (PP + 0.05% antistatic agent C); Atomizing cup 6-6: Atomizing cup (PLA + 0.05% antistatic agent C) and cup lid (PLA + 0.05% antistatic agent C); Atomizing cups 6-7: Atomizing cup (PP + 0.05% antistatic agent D) and cup lid (PP + 0.05% antistatic agent D); Atomizing cups 6-8: Atomizing cup (PLA + 0.05% antistatic agent D) and cup lid (PLA + 0.05% antistatic agent D); Atomizing cup 7-1: Atomizing cup (PP + 0.5% antistatic agent A) and cup lid (PP + 0.5% antistatic agent A); Atomizing cup 7-2: Atomizing cup (PLA + 0.5% antistatic agent A) and cup lid (PLA + 0.5% antistatic agent A); Atomizing cup 7-3: Atomizing cup (PP + 0.5% antistatic agent B) and cup lid (PP + 0.5% antistatic agent B); Atomizing cup 7-4: Atomizing cup (PLA + 0.5% antistatic agent B) and cup lid (PLA + 0.5% antistatic agent B); Atomizing cup 7-5: Atomizing cup (PP + 0.5% antistatic agent C) and cup lid (PP + 0.5% antistatic agent C); Atomizing cup 7-6: Atomizing cup (PLA + 0.5% antistatic agent C) and cup lid (PLA + 0.5% antistatic agent A); Atomizing cup 7-7: Atomizing cup (PP + 0.5% antistatic agent D) and cup lid (PP + 0.5% antistatic agent D); Atomizing cups 7-8: Atomizing cup (PLA + 0.5% antistatic agent D) and cup lid (PLA + 0.5% antistatic agent D); Atomizing cup 8-1: Atomizing cup (PP + 5% antistatic agent A) and cup lid (PP + 5% antistatic agent A); Atomizing cup 8-2: Atomizing cup (PLA + 5% antistatic agent A) and cup lid (PLA + 5% antistatic agent A); Atomizing cup 8-3: Atomizing cup (PP + 5% antistatic agent B) and cup lid (PP + 5% antistatic agent B); Atomizing cup 8-4: Atomizing cup (PLA + 5% antistatic agent B) and cup lid (PLA + 5% antistatic agent B); Atomizing cup 8-5: Atomizing cup (PP + 5% antistatic agent C) and cup lid (PP + 5% antistatic agent C); Atomizing cup 8-6: Atomizing cup (PLA + 5% antistatic agent C) and cup lid (PLA + 5% antistatic agent C); Atomizing cup 8-7: Atomizing cup (PP + 5% antistatic agent D) and cup lid (PP + 5% antistatic agent D); Atomizing cup 8-8: Atomizing cup (PLA + 5% antistatic agent D) and cup lid (PLA + 5% antistatic agent D); Atomizing cup 9-1: Atomizing cup (PP + 6% antistatic agent A) and cup lid (PP + 6% antistatic agent A); Atomizing cup 9-2: Atomizing cup (PLA + 6% antistatic agent A) and cup lid (PLA + 6% antistatic agent A); Atomizing cup 9-3: Atomizing cup (PP + 6% antistatic agent B) and cup lid (PP + 6% antistatic agent B); Atomizing cup 9-4: Atomizing cup (PLA + 6% antistatic agent B) and cup lid (PLA + 6% antistatic agent B); Atomizing cup 9-5: Atomizing cup (PP + 6% antistatic agent C) and cup lid (PP + 6% antistatic agent C); Atomizing cup 9-6: Atomizing cup (PLA + 6% antistatic agent C) and cup lid (PLA + 6% antistatic agent C); Atomizing cup 9-7: Atomizing cup (PP + 6% antistatic agent D) and cup lid (PP + 6% antistatic agent D); Atomizing cup 9-8: Atomizing cup (PLA + 6% antistatic agent D) and cup lid (PLA + 6% antistatic agent D); Atomizing cup 10-1: Atomizing cup (PP + 10% antistatic agent A) and cup lid (PP + 10% antistatic agent A); Atomizing cup 10-2: Atomizing cup (PLA + 10% antistatic agent A) and cup lid (PLA + 10% antistatic agent A); Atomizing cup 10-3: Atomizing cup (PP + 10% antistatic agent B) and cup lid (PP + 10% antistatic agent B); Atomizing cup 10-4: Atomizing cup (PLA + 10% antistatic agent B) and cup lid (PLA + 10% antistatic agent B); Atomizing cup 10-5: Atomizing cup (PP + 10% antistatic agent C) and cup lid (PP + 10% antistatic agent C); Atomizing cup 10-6: Atomizing cup (PLA + 10% antistatic agent C) and cup lid (PLA + 10% antistatic agent C); Atomizing cup 10-7: Atomizing cup (PP + 10% antistatic agent D) and cup lid (PP + 10% antistatic agent D); Atomizing cup 10-8: Atomizing cup (PLA + 10% antistatic agent D) and cup lid (PLA + 10% antistatic agent D); Atomizing cup 11-1: Atomizing cup (PP + 0.1% antistatic agent A) and cup lid (PP + 0.1% antistatic agent A); Atomizing cup 11-2: Atomizing cup (PLA + 0.1% antistatic agent A) and cup lid (PLA + 0.1% antistatic agent A); Atomizing cup 11-3: Atomizing cup (PP + 0.1% antistatic agent B) and cup lid (PP + 0.1% antistatic agent B); Atomizing cup 11-4: Atomizing cup (PLA + 0.1% antistatic agent B) and cup lid (PLA + 0.1% antistatic agent B); Atomizing cup 11-5: Atomizing cup (PP + 0.1% antistatic agent C) and cup lid (PP + 0.1% antistatic agent C); Atomizing cup 11-6: Atomizing cup (PLA + 0.1% antistatic agent C) and cup lid (PLA + 0.1% antistatic agent C); Atomizing cup 11-7: Atomizing cup (PP + 0.1% antistatic agent D) and cup lid (PP + 0.1% antistatic agent D); Atomizing cup 11-8: Atomizing cup (PLA + 0.1% antistatic agent D) and cup lid (PLA + 0.1% antistatic agent D); Atomizing cup 12-1: Atomizing cup (PP + 12% antistatic agent A) and cup lid (PP + 12% antistatic agent A); Atomizing cup 12-2: Atomizing cup (PLA + 12% antistatic agent A) and cup lid (PLA + 12% antistatic agent A); Atomizing cup 12-3: Atomizing cup (PP + 12% antistatic agent B) and cup lid (PP + 12% antistatic agent B); Atomizing cup 12-4: Atomizing cup (PLA + 12% antistatic agent B) and cup lid (PLA + 12% antistatic agent B); Atomizing cup 12-5: Atomizing cup (PP + 12% antistatic agent C) and cup lid (PP + 12% antistatic agent C); Atomizing cup 12-6: Atomizing cup (PLA + 12% antistatic agent C) and cup lid (PLA + 12% antistatic agent C); Atomizing cup 12-7: Atomizing cup (PP + 12% antistatic agent D) and cup lid (PP + 12% antistatic agent D); Atomizing cup 12-8: Atomizing cup (PLA + 12% antistatic agent D) and cup lid (PLA + 12% antistatic agent D);

[0075] 3. Detection conditions Detection device: Laser particle size analyzer manufactured by SYMPATEC for measuring HELOS&INHALER inhalation aerosols and powdered inhalants. Detection / Inhalation Method: Detection occurs 20 seconds after atomization. Number of repetitions per set: 3. Detection criteria: Duration of optical concentration Copt (Optical Concentration / %) ≥ 20% and the optical concentration at the corresponding time point.

[0076] 4. Experimental Results and Analysis The area under the optical density-time curve of the mist was calculated and recorded as "AUC" (%*S), representing the amount of mist. The material of the atomizing cup was then examined using the amount of mist as an indicator. The results are shown in Figure 7.

[0077] Results and analysis: When 0.1 ml of recombinant COVID-19 vaccine dilution was atomized using an untreated atomizing cup, the mist rapidly condensed on the cup wall, and a very small amount of mist remained in the cup 20 seconds after atomization. When the atomizing cup was purged with an ion gun to remove static electricity before being used to contain the mist, the inhalable volume improved after 20 seconds, but the effect was still insufficient. Adding 0.03% antistatic agent to the atomizing cup improved both the antistatic effect and the amount of mist. Adding 0.05% or 0.5% antistatic agent further improved the cup's mist containment performance, and this effect was clearly higher than that achieved by removing static electricity with an ion gun. At 6% and 10% additive levels, the dose-effect relationship showed improved antistatic properties, but decreased mist volume. Amount of residue remaining in the cup body and cup lid after atomization is complete Before the experiment, the weight of the cup body and lid was measured using a 1 / 10,000 electronic balance. After atomization was complete and mist inhalation was finished, the weight was measured again using the 1 / 10,000 electronic balance. Chemical solution residual rate = (weight after atomization - weight before atomization) / weight of atomized chemical solution x 100% The results are shown in the table below.

[0078] TIFF0007843744000002.tif245170TIFF0007843744000003.tif164170

[0079] TIFF0007843744000004.tif231170

[0080] Results and analysis: The amount of residual chemical mist in the atomizing cups constantly changed as the antistatic agent content varied. When the antistatic agent content was between 0.03% and 10%, the amount of residual chemical mist in the atomizing cups was low, resulting in performance superior to or nearly identical to atomizing cups treated with an ion gun for static electricity removal. When the antistatic agent content was between 0.05% and 5%, the effect of preventing residual chemical mist in each atomizing cup was optimized. Example 3: Effect of inhalation using an atomizing cup on the particle size of vaccine particles

[0081] 1. Experimental Objectives We will examine the mist containment effect of the antistatic atomizing cup.

[0082] 2. Experimental Design Model atomized drug: Recombinant COVID-19 vaccine manufactured by CanSino (adenovirus type 5 vector, liquid formulation). Atomization amount: 0.1ml. Atomization cups: The 6-1, 6-3, 7-1, 7-3, 8-1, and 8-3 atomization cups from Example 2 were used for the study.

[0083] 3. Detection conditions Detection device: Particle size analyzer for inhaled formulations. Detection conditions: Detection is performed 10 seconds after atomization. Detection item: Particle size (X 10.3 , X 50.3 , X 90.3 ), the percentage of particles with a particle size of less than 5.25 μm.

[0084] 4. Experimental Results and Analysis The aerodynamic distribution of aerosol atomized using an atomizing cup was detected using an inhalation formulation particle size analyzer, and the results of three parallel detections are shown in the table below.

[0085] TIFF0007843744000005.tif54170

[0086] Results and analysis: When using a PP atomizing cup and adjusting the antistatic agent content to 0.05% to 5%, the proportion of aerodynamically sized mist particles and particles smaller than 5.25 μm were similar, with no significant difference, thus meeting the requirements for atomized inhalation administration. Example 4: Comparison of inhalable volume using an antistatic atomizing cup inhalation method and a commercially available mouth inhalation method.

[0087] 1. Experimental Objectives Conventional nebulization inhalation (i.e., oral inhalation) involves breathing while atomizing the drug, delivering it to the lungs through respiration. In nebulization cup inhalation, the mist is collected in a nebulization cup and then inhaled in one mouth. In this example, we investigate the amount of drug administered by a method in which mist is collected in an antistatic nebulization cup and then inhaled in one mouth, and compare it with the inhalation method using a suction nozzle.

[0088] 2. Experimental Design Model atomizing agent: Recombinant COVID-19 vaccine (adenovirus type 5 vector) liquid formulation manufactured by CanSino. Atomization amount: 0.1ml. Atomization cup: The atomization cup 6-1 from Example 2 will be used for the investigation.

[0089] 3. Detection conditions Oral inhalation method: In the adult breathing mode of the breathing simulator, inhalable drugs are collected in a filtration membrane. Atomization cup suction method: The pumping suction speed was adjusted to 15 L / min, and the filter membrane fixing device was connected to the pump. After 10 seconds of atomization, the opening of the cup was connected to the connection port of the filter membrane, and the mist was collected in the filter membrane.

[0090] 4. Experimental Results and Analysis Each method was repeated six times. After completion, the vaccine was eluted from the filtration membrane, and the virus particles were quantified using the ELISA method. The results are shown in the table below.

[0091] TIFF0007843744000006.tif83170

[0092] Results and analysis: The results showed that the amount of medication that could be inhaled during administration using the atomizing cup was 48.3%, and there was no significant difference compared to the method using oral inhalation. This suggests that the atomizing cup can function as a substitute for oral inhalation.

[0093] The above are merely preferred embodiments of the present invention and do not limit the present invention. Any modifications, equivalent substitutions, etc., made without departing from the spirit and principles of the present invention are all included within the scope of the patent of the present invention.

[0094] The embodiments and methods described in this invention may vary depending on the skill, experience, and preferences of those skilled in the art.

[0095] In this invention, the steps of the method are presented in a predetermined order, but these do not limit the order of the steps of the method in any way.

Claims

1. A atomizing cup, The cup body and cup lid are included, the cup body being made of plastic, the cup body having an antistatic agent added, the antistatic agent content of the cup body being 0.05% to 0.5% by mass, the cup lid having an antistatic agent added, the antistatic agent content of the cup lid being 0.05% to 0.5% by mass, The aforementioned atomizing cup is used for the atomized inhalation administration of vaccines. The atomizing cup is characterized in that a mist intake port and a suction nozzle are opened in the cup lid.

2. The atomizing cup according to claim 1, characterized in that the material of the cup body is a transparent plastic selected from polypropylene (PP), polylactic acid (PLA), polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), and polycarbonate (PC).

3. The atomizing cup according to claim 1, characterized in that the material of the cup lid is a plastic selected from polypropylene (PP), polylactic acid (PLA), polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), and polycarbonate (PC).

4. The atomizing cup according to any one of claims 1 to 3, characterized in that the antistatic agent is one or more selected from anionic antistatic agents, amphoteric antistatic agents, nonionic antistatic agents, and polymeric antistatic agents.

5. The atomizing cup according to claim 4, characterized in that the anionic antistatic agent is one or more selected from alkyl sulfonates, alkyl phosphates, copolymer salts of maleic anhydride and other monomers, polyacrylates and polystyrene sulfonates, the amphoteric antistatic agent is an amphoteric alkylimidazoline salt and / or alkyl amino acid, the nonionic antistatic agent is a fatty acid polyhydric alcohol ester and / or polyoxyethylene adduct, and the polymeric antistatic agent is one or more selected from polyoxyethylene fatty acid ethers, polyoxyethylene alkylphenyl ethers, polyethylene glycol fatty acid esters and polyacrylic acid derivatives.

6. The atomizing cup according to claim 5, characterized in that the nonionic antistatic agent is one or more selected from fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, and glycerin monofatty acid ester; the amphoteric antistatic agent is alkyldicarboxymethylammonium ethyl lactone and / or dodecyldimethyl betaine; and the polymeric antistatic agent is one or more selected from ethylenediamine ethylene oxide dopylene oxide, poly-4-vinylpyridine type polysoap, octylstyrene, and styrene sulfonic acid copolymer type polysoap.

7. The atomizing cup according to claim 1, characterized in that the volume of the atomizing cup is 300 to 800 ml.

8. The atomizing cup according to claim 1, characterized in that the atomizing cup is a disposable type atomizing cup.

9. A method for manufacturing an atomizing cup according to any one of claims 1 to 3, A manufacturing method characterized by comprising the step of adding an antistatic agent component or an antistatic masterbatch to the raw materials for manufacturing the cup body and the cup lid.

10. A atomizing inhalation administration device characterized by having an atomizing cup according to any one of claims 1 to 3.

11. The atomizing inhalation administration device according to claim 10, further characterized by having an atomizer.

12. The atomizing inhalation administration device according to claim 11, characterized in that the atomizer is an ultrasonic atomizer, a compression atomizer, or a vibrating screen atomizer.

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