Atomizing cup and use of the same in atomization inhalation administration

Abstract

To provide an atomizing cup for atomization inhalation administration of medicine (for example, SARS-CoV-2 vaccine) preventing and / or treating respiratory diseases, and a method for using the same.SOLUTION: An atomizing cup can effectively maintain stability of medicine aerosol within a fixed time when an anti-static agent is added, can stabilize the state of particle diameter, have fewer medicine residue in the cup, secure an effective inhalable quantity, easily and simply be administered, clearly improve vaccination efficiency, and can be applied to a large-scale vaccination.SELECTED DRAWING: Figure 7

Description

Technical Field

[0001] The present invention relates to the technical field of biopharmaceuticals, and specifically to a nebulizing cup and its use in nebulized inhalation administration, particularly its use in nebulized inhalation administration of drugs for preventing and / or treating respiratory diseases (such as SARS-CoV-2 vaccines).

Background Art

[0002] Currently, one treatment method for respiratory diseases is nebulized inhalation administration, which uses a nebulizer to disperse a drug solution into fine droplets and inhales them through the patient's 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, acute pneumonia, etc.

[0003] A nebulized inhalation vaccine is a vaccine that immunizes by nebulized inhalation. So-called nebulized inhalation immunization is a method in which a vaccine is nebulized into fine particles by a nebulizer and inhaled by breathing, and these fine particles enter the airway and lungs to elicit mucosal immunity.

[0004] The equipment and devices for realizing this nebulized inhalation treatment and immunization are very important for the implementation and quality of treatment and immunization, and have attracted great attention from researchers. Existing nebulized administration devices in the prior art mainly administer drugs in a way of inhaling while nebulizing, and it is necessary to guide the subject before administration. Since many children and even adults often have inappropriate control of the frequency of inhalation administration and self-breathing, it greatly affects the inhalation and absorption of drug mists, which is very disadvantageous for immunization. Also, for immunization, in order to prevent cross-infection, the device for the subject to inhale is required to be disinfected and discarded after use. In view of the need for large-scale vaccination, it is an urgent task to provide a nebulized administration device that can prevent cross-infection while reducing costs and has high inhalation vaccination efficiency.

[0005] Also, when performing nebulized inhalation using a nebulizer cup, the nebulized medicine mist is likely to liquefy on the cup wall due to the action of static electricity and become droplets, and it cannot be normally inhaled by the human body. Therefore, in order to prevent the liquefied residue of the medicine mist, it is necessary to add an antistatic agent to the nebulizer cup to resist static electricity. However, the amount of the antistatic agent used also has a great impact on the medicine mist. When the content of the antistatic agent is low, there is a lot of deposition of the medicine mist and the residual amount is large. When the content of the antistatic agent is high, it may have an adverse effect on the molding of the cup body, the touch feeling, and the effective amount of the medicine mist after nebulization. Therefore, it is urgent to find an appropriate antistatic agent, the optimal antistatic agent and its content in order to ensure the effectiveness of the medicine nebulization.

Summary of the Invention

Problems to be Solved by the Invention

[0006] In order to overcome the drawbacks of the prior art, the present invention provides a nebulizer cup that collects and accommodates the medicine mist generated by a nebulizer and allows a subject to inhale it, which has effects such as treatment and immunity, and its use.

Means for Solving the Problems

[0007] In a first aspect of the present invention, there is provided a nebulizer cup including a cup body and a cup lid, and 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 is an anionic antistatic agent (e.g., alkyl sulfonates, alkyl phosphates, copolymer salts of maleic anhydride and other monomers, polyacrylates, polystyrene sulfonates), an amphoteric ion antistatic agent (e.g., amphoteric alkyl imidazoline salts, alkyl amino acids), a nonionic antistatic agent (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 ethers, polyoxyethylene alkyl phenyl ethers, polyoxyethylene alkyl amines, etc.), a polymeric antistatic agent (e.g., polyoxyethylene fatty ethers, polyoxyethylene alkyl phenyl ethers, polyethylene glycol fatty acid esters, polyacrylic acid derivatives) and a combination of one or more of these, and particularly may be a nonionic antistatic agent and / or a polymeric antistatic agent.

[0010] Furthermore, the nonionic antistatic agent is preferably a combination of one or more of fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, and glycerin monofatty acid ester, the amphoteric ion antistatic agent is preferably alkyldicarboxymethylammonium ethyl lactone and / or dodecyldimethylbetaine, and the polymeric antistatic agent is preferably a combination of one or more of an ethylene oxide-propylene oxide adduct of ethylenediamine, a poly(4-vinylpyridine) type polysulfonate, octylstyrene, and a styrene sulfonic acid copolymer type polysulfonate.

[0011] Cationic quaternary amine salts have high adhesion to polymer materials, are excellent in antistatic properties, and are antistatic agents commonly used in plastics. However, they are irritating to the skin and toxic, so they are not within the scope of the present 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 by adding an antistatic masterbatch to the manufacturing raw materials, particularly by adding an antistatic masterbatch to the manufacturing raw materials. Appropriate commercially available products may be used for the antistatic agent and the antistatic masterbatch according to the plastic material 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 protrudes from the cup lid and communicates with the space inside the cup body. It may have any shape suitable for the subject to inhale the mist, such as tubular or conical. The suction inlet end of the suction nozzle may have any shape suitable for the subject to inhale, such as circular or elliptical. To seal the suction nozzle until the atomizing cup is used, a sealing member may be further provided at the suction inlet of the suction nozzle.

[0019] Specifically, the material of the cup lid is plastic, especially medical-grade plastic, such as polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), polycarbonate (PC), polylactic acid (PLA), etc., and especially PP or PLA may be used. Specifically, the cup lid is 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), polylactic acid (PLA), etc., and especially PP or PLA may be used. Specifically, the cup body is transparent.

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

[0022] Specifically, the shape of the cup body may be any appropriate shape, such as cylindrical or an inverted frustum of a cone with a reduced diameter from top to bottom.

[0023] Specifically, a handle may be further provided on the side wall of the cup body to facilitate gripping the atomizing cup.

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

[0025] In a second aspect of the present invention, there is provided a method for manufacturing an atomizing cup according to the first aspect, including 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 material for manufacturing the cup lid.

[0027] Specifically, the method may further include a molding step, and is molded by methods such as extrusion, injection molding, compression molding, blow molding, etc.

[0028] In a third aspect of the present invention, there is provided the use of the atomizing cup according to the first aspect in the manufacture of an atomizing inhalation administration device.

[0029] Specifically, the use is the use of the above atomizing cup in the manufacture of an atomizing inhalation administration device for drugs for preventing and / or treating respiratory diseases.

[0030] Specifically, the device includes the atomizing cup according to the first aspect of the present invention and an atomizer. More specifically, the atomizer may be a suitable atomizer such as an ultrasonic atomizer, a compression atomizer, a vibrating sieve atomizer, etc., particularly a vibrating sieve atomizer.

[0031] Specifically, the drug is a vaccine, such as a pneumococcal vaccine, an influenza vaccine, a coronavirus vaccine, a varicella vaccine, a Newcastle disease virus vaccine, a measles vaccine, a tuberculosis vaccine, a mite allergy vaccine, etc.

[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 also contain genes (full length or partial sequences) of other structural proteins of SARS-CoV-2 (e.g., M protein, E protein, N protein).

[0034] Specifically, the adenovirus may be a human adenovirus (e.g., AdHu2 type, AdHu5 type, etc.) or an animal adenovirus vector such as a chimpanzee adenovirus vector (e.g., 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 9 ~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 (e.g., 0.05, 0.1, 0.2, 0.3, 0.4, 0.5 ml), particularly 0.05~0.2 ml, and 0.1 ml.

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

[0038] Specifically, the nebulizer may be a suitable nebulizer such as an ultrasonic nebulizer, a compression nebulizer, a vibrating sieve nebulizer, etc., particularly a vibrating sieve nebulizer.

[0039] In a fifth aspect of the present invention, there is provided the use of the nebulizing cup described in the first aspect in nebulized inhalation administration.

[0040] Specifically, the use is the use of the above nebulizing cup in the nebulized inhalation administration of a drug for preventing and / or treating a respiratory disease.

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

[0042] In a sixth aspect of the present invention, there is provided a nebulized inhalation administration method including the step of administering a drug to a subject with the nebulizing cup described in the first aspect.

[0043] Specifically, the method is a nebulized inhalation immunization method, where the drug is a vaccine, such as a pneumococcal vaccine, an influenza vaccine, a coronavirus vaccine, a varicella vaccine, a Newcastle disease virus vaccine, a measles vaccine, a tuberculosis vaccine, a mite allergy vaccine, etc. 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 into which the S protein gene of SARS-CoV-2 is inserted. More specifically, the above recombinant adenovirus may further contain genes (full-length or partial sequences) of other structural proteins of SARS-CoV-2 (such as M protein, E protein, N protein).

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

[0046] Specifically, the content of the recombinant adenovirus in the recombinant adenovirus vector vaccine is 1×10 9 ~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).

[0047] Specifically, the unit dose of the vaccine 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.

[0048] Specifically, the method includes step (1) of atomizing the drug by an atomizer, step (2) of collecting the drug mist generated in step (1) by the atomizing cup, and step (3) in which the subject inhales the drug mist through the suction nozzle of the atomizing cup.

[0049] Specifically, step (3) is performed within 30 seconds (s) after mist collection (such as 20 s, 15 s, 10 s, 5 s), particularly within 10 s after completion of mist collection.

[0050] Specifically, the atomizer in step (1) may be a suitable atomizer such as an ultrasonic atomizer, a compression atomizer, a vibrating sieve atomizer, particularly a vibrating sieve atomizer.

[0051] As shown in FIGS. 1 to 6, the atomizing cup includes a cup body 1 and a cup lid 2. The cup lid includes an atomizing port 21, a reverse stopper 22, a connection portion 23 between the reverse stopper and the cup lid, a suction nozzle 24, a plug 25, a positioning thread 26, and a pull tab 27. When the pull tab 27 is held by hand to open the reverse stopper 22, the atomizer is connected to the cup through the atomizing port 21, and the mist generated when atomizing the chemical solution enters the cup through the atomizing port 21. The subject can receive inoculation by inhaling the mist through the suction nozzle 24. After the inoculation is completed, hold the plug 2-5 by hand and pull the positioning thread 26 to break it, and then place the plug 25 over the suction nozzle 24 to seal the suction nozzle 24. Also, press the reverse stopper 22 downward to flush with the surface of the cup lid to seal the atomizing port 21. Sealing the suction nozzle 24 and the atomizing port 21 can prevent the mist remaining in the cup from overflowing into the air and protect the environment from contamination by biological products.

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

[0053] Furthermore, the cup lid 2 further includes a plug 25. An insertion portion 251 is provided at the lower end of the plug 25. The plug 25 is inserted into the suction nozzle 24. 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 suction nozzle 24 can be sealed.

[0054] Furthermore, the plug 25 has a positioning portion 252 extending outwardly around the circumference so as to be perpendicular to the insertion portion 251, and the contour size of the positioning portion 252 is larger than the contour size of the insertion portion 251.

[0055] Furthermore, in the plug 25, a hand-held portion 253 is provided at the upper end perpendicular to the positioning portion, and the attachment and detachment of the plug 25 can be manually performed.

[0056] Furthermore, the plug 25 is located at 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 inversion stopper 22, there is a rectangular pull tab 27 perpendicular to the inversion stopper 22 at a location near the edge.

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

[0059] Specifically, the atomizing cup is of a disposable type in order to avoid cross-infection.

Advantages of the Invention

[0060] The atomizing cup according to the present invention can be used for the atomizing inhalation administration of drugs for preventing and / or treating respiratory system diseases. Atomizing treatment is mainly aerosol inhalation therapy. So-called aerosol is fine solid or liquid particles floating in the air. Therefore, aerosol inhalation therapy is to disperse a drug into fine droplets or particles using an atomizing device, suspend them in a gas, and inhale them into the respiratory tract or lungs. When the fog-like particles deposit, the properties of the fog-like particles are affected. The physical mechanisms causing the deposition of fog-like particles include impaction deposition, gravitational deposition, diffusion deposition, electrostatic adsorption deposition, and interception deposition. In order to eliminate the influence on fog-like particles caused by the deposition action caused by electrostatic adsorption, in previous studies, when a food-grade antistatic agent such as a raw material of edible vegetable oil was added to a drug preparation, the volume of the atomized particles became larger than 20 μm, and delivery became impossible. When treated with an electrostatic elimination device (such as an ion bar, ion gun, ion fan, etc.) that has a reliable electrostatic elimination effect immediately before using the atomizing cup, it has a certain effect on the deposition of the formulation fog-like particles, but it is not significant.

[0061] In the present invention, by adding an antistatic agent to the material of the atomization cup, the combination of the transparent plastic material and the antistatic agent enables the water droplets to maintain stability by themselves, thereby obtaining a suitable atomization effect. The reason is that the principle of antistatic is considered to be to form a conductive layer on the surface of the material to lower its surface resistivity and quickly leak the electrostatic charges that have already occurred. When an antistatic agent is directly added to a transparent plastic material, in addition to exerting an antistatic effect, adding the antistatic agent may improve the smoothness of the surface of the plastic material and reduce the blocking deposition due to the friction between the mist particles and the surface of the plastic material. Since the addition of the antistatic agent is not just an antistatic effect or a smoothing effect, the present invention takes the total amount of mist, the inhalable amount of mist, the chemical liquid residue rate, and the aerodynamics of the aerosol after atomization as comprehensive indicators, and examines the specific usage amount of the antistatic agent in the atomization cup. It is found that when the usage amount of the antistatic agent is 0.03% - 10% (mass percentage), the usage needs can be met, and when the usage amount of the antistatic agent is 0.05 - 5% (mass percentage), the comprehensive indicators are more excellent. Specifically, without adding an antistatic agent, the atomization cup made of transparent plastic has poor ability to carry mist, a high chemical liquid residue rate, and is almost in an unusable state. When the usage amount is 0.03%, the antistatic effect and the comprehensive performance of mist inhalation will decrease to some extent. On the other hand, when the addition amount increases to 6% or 10%, the antistatic property improves in terms of the dose-effect relationship, but the comprehensive performance of mist inhalation decreases. From this, it can be seen that adding a specific amount of the antistatic agent is effective in maintaining the stability of the drug mist for a certain period of time (for example, within 20 seconds). Its particle size state is stable, the drug residue in the cup is small, and an effective inhalation amount and deposition rate can be ensured. The structural design of the atomization cup further enhances the inhalation performance. Especially when applied in the vaccine field, the administration operation is simple and convenient, the inoculation efficiency can be significantly improved, and it can be used for large-scale inoculation.

Brief Description of the Drawings

[0062]

Figure 1

Figure 2

Figure 3

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Figure 6

Figure 7

Modes for Carrying Out the Invention

[0063] Unless otherwise defined, all scientific and technical terms used in the present invention have the same meaning as commonly understood by those skilled in the art of the present invention.

[0064] In the present invention, "subject" means a human who receives the administration method (especially the atomizing inhalation immunization method) of the present invention.

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

[0066] Hereinafter, with reference to the embodiments of the present invention, the technical aspects of the present invention will be clearly and completely described. However, it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative efforts belong to the patent scope of the present invention. Example 1: Influence of Antistatic Agents on Mist Containment in the Atomizing Cup

[0067] 1. Experimental Purpose: Examine the mist containment effect of the atomizing cup added with each antistatic agent.

[0068] 2. Experimental Design Atomizing model drug: Recombinant novel coronavirus vaccine (type 5 adenovirus vector) liquid preparation manufactured by CanSino Atomizing amount: 0.1 ml. Antistatic agent A: Fatty acid alcohol polyoxyethylene ester (anionic antistatic agent) Antistatic agent B: Sodium secondary alkyl sulfonate (anionic 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 dicarboxymethyl ammonium ethyl lactone (zwitterionic antistatic agent) Antistatic agent H: Dodecyl dimethyl betaine (zwitterionic antistatic agent) Atomizing cups treated in various ways: Atomizing cup 1: Atomizing 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: Detect after atomizing for 20 s. Number of repetitions per group: 3 times.

[0069] 3. Detection Conditions Detection Device: One - ten - thousandth electronic balance;

[0070] 4. Experimental Results and Analysis When 0.1 ml of the recombinant novel coronavirus vaccine diluent is atomized and a PP - material atomizing cup without any treatment is used, the mist rapidly condenses on the cup wall, and there is a very small amount of mist in the cup 20 seconds after atomization. When 0.1% of anionic, non - ionic or polymer - type antistatic agent is added to the atomizing cup, both the antistatic effect and the amount of mist are improved. Residual amount in the cup body + cup lid after atomization Before the experiment, the weight of the cup body + cup lid was weighed using a one - ten - thousandth electronic balance. After atomization and completion of mist inhalation, the weight was weighed again using a one - ten - thousandth electronic balance. Drug solution residue rate = (weight after atomization - weight before atomization) / weight of atomized drug solution × 100% The results are shown in the following table.

[0071] Table 1 Influence of antistatic agent on the residual amount of contained mist

Table 1

[0072] Results and Analysis: When atomization was carried out using an atomization cup without any treatment, a large amount of mist remained in the cup. The atomization cup with an amphoteric ion type antistatic agent had significantly improved mist containment performance. On the other hand, the atomization cups with anionic, nonionic, or polymer type antistatic agents had significantly improved mist containment performance. Example 2 Influence of antistatic agents with different contents on mist containment of atomization cups

[0073] 1. Experimental purpose: To examine the effect of mist containment of atomization cups treated by each method.

[0074] 2. Experimental design Atomization model drug: Recombinant novel coronavirus vaccine (adenovirus vector type 5) liquid preparation manufactured by CanSino Atomization amount: 0.1 ml. Antistatic agent A: Polymer 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 ion type, dodecyldimethylbetaine Atomization cups treated by each method: Atomization cup 1: Atomization cup (PP) and cup lid (PP); Atomization cup 2: Atomization cup (PLA) and cup lid (PLA); Atomization cup 3: Atomization cup (PP) and cup lid (PP), electrostatic removal by ion gun; Atomization cup 4: Atomization cup (PLA) and cup lid (PLA), electrostatic removal by ion gun; Atomization cup 5-1: Atomization cup (PP + 0.03% antistatic agent A) and cup lid (PP + 0.03% antistatic agent A); Atomization cup 5-2: Atomization cup (PLA + 0.03% antistatic agent A) and cup lid (PLA + 0.03% antistatic agent A); Atomization cup 5-3: Atomization 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 cup 5-6: Atomizing cup (PLA + 0.03% antistatic agent C) and cup lid (PLA + 0.03% antistatic agent C); Atomizing cup 5-7: Atomizing cup (PP + 0.03% antistatic agent D) and cup lid (PP + 0.03% antistatic agent D); Atomizing cup 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 cup 6-7: Atomizing cup (PP + 0.05% antistatic agent D) and cup lid (PP + 0.05% antistatic agent D); Atomizing cup 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 cup 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); Atomization Cup 11-3: Atomization cup (PP + 0.1% Antistatic Agent B) and cup lid (PP + 0.1% Antistatic Agent B); Atomization Cup 11-4: Atomization cup (PLA + 0.1% Antistatic Agent B) and cup lid (PLA + 0.1% Antistatic Agent B); Atomization Cup 11-5: Atomization cup (PP + 0.1% Antistatic Agent C) and cup lid (PP + 0.1% Antistatic Agent C); Atomization Cup 11-6: Atomization cup (PLA + 0.1% Antistatic Agent C) and cup lid (PLA + 0.1% Antistatic Agent C); Atomization Cup 11-7: Atomization cup (PP + 0.1% Antistatic Agent D) and cup lid (PP + 0.1% Antistatic Agent D); Atomization Cup 11-8: Atomization cup (PLA + 0.1% Antistatic Agent D) and cup lid (PLA + 0.1% Antistatic Agent D); Atomization Cup 12-1: Atomization cup (PP + 12% Antistatic Agent A) and cup lid (PP + 12% Antistatic Agent A); Atomization Cup 12-2: Atomization cup (PLA + 12% Antistatic Agent A) and cup lid (PLA + 12% Antistatic Agent A); Atomization Cup 12-3: Atomization cup (PP + 12% Antistatic Agent B) and cup lid (PP + 12% Antistatic Agent B); Atomization Cup 12-4: Atomization cup (PLA + 12% Antistatic Agent B) and cup lid (PLA + 12% Antistatic Agent B); Atomization Cup 12-5: Atomization cup (PP + 12% Antistatic Agent C) and cup lid (PP + 12% Antistatic Agent C); Atomization Cup 12-6: Atomization cup (PLA + 12% Antistatic Agent C) and cup lid (PLA + 12% Antistatic Agent C); Atomization Cup 12-7: Atomization cup (PP + 12% Antistatic Agent D) and cup lid (PP + 12% Antistatic Agent D); Atomization Cup 12-8: Atomization cup (PLA + 12% Antistatic Agent D) and cup lid (PLA + 12% Antistatic Agent D);

[0075] 3. Detection Conditions Detection Device: HELOS&INHALER laser particle size analyzer manufactured by SYMPATEC for measuring inhaled aerosols and powder inhalants. Detection / Inhalation Method: Detect after atomization for 20 s. Number of repetitions per set: 3 times. Detection Index: Duration in the range where the optical density Copt (Optical Concentration / %) ≥ 20% and the optical density 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 denoted as "AUC" (%*S), which represents the amount of mist. The material of the atomization cup was examined using the mist amount as an index. The results are shown in Fig. 7.

[0077] Results and Analysis: When 0.1 ml of the recombinant novel coronavirus vaccine diluent was atomized and an atomization cup without any treatment was used, the mist rapidly condensed on the cup wall, and there was a very small amount of mist in the cup after 20 s of atomization. After the atomization cup was purged with an ion gun to remove static electricity and then used to contain the mist, the inhalable amount was improved after 20 s of atomization, but the effect was still insufficient. When 0.03% of an antistatic agent was added to the atomization cup, both the antistatic effect and the mist amount were improved. When 0.05% or 0.5% of the antistatic agent was added to the atomization cup, the mist containment performance of the cup was further improved, and the effect was significantly higher than that when static electricity was removed with an ion gun. When the addition amounts were 6% and 10%, according to the dose-effect relationship, the antistatic property was improved, but the mist amount decreased. Residual amount in the cup body + cup lid after atomization Before the experiment, the weight of the cup body + cup lid was weighed using a 1 / 10000 electronic balance. After atomization and completion of mist inhalation, the weight was weighed again using a 1 / 10000 electronic balance. Drug solution residue rate = (weight after atomization - weight before atomization) / weight of atomized drug solution × 100% The results are shown in the following table.

[0078] Table 2 AUC amount of drug solution for each atomization cup

Table 2

[0079] Table 3 Average residual rate of the chemical solution in each atomizing cup

Table 3

[0080] Results and analysis: When the content of the antistatic agent changed, the residual amount of the chemical solution mist in the atomizing cup also changed continuously. When the content of the antistatic agent was 0.03% - 10%, the residual amount of the chemical solution mist in the atomizing cup was small, and the result was better than or almost the same as that of the atomizing cup treated with electrostatic removal by an ion gun. When the content of the antistatic agent was 0.05% - 5%, the effect of preventing the residual of the chemical solution mist in each atomizing cup was optimal. Example 3 Influence on the particle size of vaccine particles by inhalation using an atomizing cup

[0081] 1. Experimental purpose Examine the mist containment effect of the antistatic atomizing cup.

[0082] 2. Experimental design Model atomizing drug: Recombinant novel coronavirus vaccine (type 5 adenovirus vector, liquid preparation) manufactured by CanSino Atomizing amount: 0.1 ml. Atomizing cup: The atomizing cups 6-1, 6-3, 7-1, 7-3, 8-1, and 8-3 of Example 2 were used for the examination.

[0083] 3. Detection conditions Detection device: Particle size measuring instrument for inhalation preparations. Detection condition: Detect 10 s after atomization. Detection item: Particle size (X 10.3 、X 50.3 、X 90.3 ), proportion of particles with a particle size less than 5.25 μm.

[0084] 4. Experimental results and analysis Using an inhalation preparation particle size analyzer, the aerodynamic distribution of the aerosol atomized using an atomization cup was detected, and the results of three parallel detections are shown in the following table.

[0085] Table 4 Aerodynamic distribution results of the aerosol after atomization

Table 4

[0086] Results and analysis: When using a PP material atomization cup and setting the content of the antistatic agent to 0.05% - 5%, the detected aerodynamic particle size of the mist and the proportion of particle sizes less than 5.25 μm were close, with no significant difference, meeting the requirements of aerosol inhalation administration. Example 4 Comparison of inhalable amounts when using the antistatic atomization cup inhalation method and a commercially available oral inhalation method

[0087] 1. Experimental purpose Conventional aerosol inhalation administration (i.e., oral inhalation) is to breathe while atomizing and deliver the drug to the lungs through breathing. In the atomization cup inhalation, after collecting the mist in the atomization cup, it is inhaled in one go. In this example, after accommodating the mist in the antistatic atomization cup, the amount of drug in the method of inhaling in one go was examined and compared with the inhalation method using a suction nozzle.

[0088] 2. Experimental design Model atomized drug: Recombinant novel coronavirus vaccine (adenovirus vector type 5) liquid preparation manufactured by CanSino Atomization amount: 0.1 ml. Atomization cup: The atomization cup 6 - 1 of Example 2 was used for the examination.

[0089] 3. Detection conditions Oral inhalation method: In the adult breathing mode of the breathing simulator, the inhalable drug is collected on the filter membrane. Atomization cup inhalation method: Adjust the pressure - feeding inhalation speed to 15 L / min, and connect the filter membrane fixing device to the pump. After atomizing for 10 s, connect the opening of the cup and the connection port of the filter membrane, and collect the mist on the filter membrane.

[0090] 4. Experimental Results and Analysis In each method, it was repeated 6 times. After completion, the vaccine on the filter membrane was eluted, and the virus particles were quantified by the ELISA method. The results are shown in the following table.

[0091] Table 5 Detection Results of Inhalable Dose

Table 5

[0092] Results and Analysis: As a result, in the method using the atomization cup, the inhalable dose at the time of administration was 48.3%, and no significant difference was observed compared with the method using oral inhalation. As a result, it was shown that the atomization cup can function as a substitute for the mouth.

[0093] The above are only 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 in the patent scope of the present invention.

[0094] The foregoing embodiments and methods described in the present invention may vary depending on the ability, experience, and preference of those skilled in the art.

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

Claims

1. An atomizing cup comprising:

1. An atomizing cup comprising a cup body and a cup cover, the cup body being made of a plastic material, and an antistatic agent being added to the cup body.

2. 2. The atomizing cup according to claim 1, wherein the content of the antistatic agent added to the cup body is 0.03% by mass to 10% by mass, preferably 0.05% by mass to 5% by mass.

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

4. 2. The atomizing cup according to claim 1, wherein the material of the cup lid is a plastic selected from the group consisting of polypropylene (PP), polylactic acid (PLA), polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), and polycarbonate (PC).

5. The atomizing cup according to claim 1, characterized in that an antistatic agent is added to the cup lid, and the content of the antistatic agent added to the cup lid is 0.03% by mass to 10% by mass, preferably 0.05% by mass to 5% by mass.

6. 2. The atomizing cup according to claim 1, wherein the cup cover is provided with a mist inlet and a suction nozzle.

7. The atomizing cup according to any one of claims 1 to 6, characterized in that the antistatic agent is one or a combination of two or more selected from the group consisting of anionic antistatic agents, amphoteric ionic antistatic agents, nonionic antistatic agents, and polymeric antistatic agents.

8. The atomizing cup according to claim 7, wherein the anionic antistatic agent is one or a combination of two or more selected from alkyl sulfonates, alkyl phosphates, copolymer salts of maleic anhydride and other monomers, polyacrylates, and polystyrene sulfonates, the amphoteric ionic antistatic agent is an amphoteric alkyl imidazoline salt and / or an alkyl amino acid, the nonionic antistatic agent is a fatty acid polyhydric alcohol ester and / or a polyoxyethylene adduct, and the polymeric antistatic agent is one or a combination of two or more selected from polyoxyethylene fatty ethers, polyoxyethylene alkyl phenyl ethers, polyethylene glycol fatty acid esters, and polyacrylic acid derivatives.

9. The atomizing cup according to claim 8, wherein the nonionic antistatic agent is one or a combination of two or more selected from fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, and glycerin mono fatty acid ester, the amphoteric ionic antistatic agent is alkyldicarboxymethylammonium ethyl lactone and / or dodecyldimethylbetaine, and the polymeric antistatic agent is one or a combination of two or more selected from ethylenediamine ethylene oxide propylene oxide adduct, poly4-vinylpyridine type polysoap, octylstyrene, and styrenesulfonic acid copolymer type polysoap.

10. The atomizing cup according to claim 1, characterized in that the volume of said atomizing cup is 300-800 ml, preferably 500 ml.

11. A method for manufacturing the atomizing cup according to any one of claims 1 to 10, A manufacturing method comprising the step of adding an antistatic agent component or an antistatic masterbatch to a manufacturing raw material of a cup body.

12. Use of the atomizing cup according to any one of claims 1 to 10 in the manufacture of an atomizing inhalation administration device.

13. The use according to claim 12, characterized in that the use is a use of the atomizing cup in the manufacture of a device for administering a drug by inhalation through atomization for preventing and / or treating a respiratory disease.

14. The use according to claim 13, characterized in that the drug is a vaccine.

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