An inhaled ascorbic acid powder mist and a method of making the same

Abstract

The application discloses an inhaled ascorbic acid powder aerosol and a preparation method thereof, and relates to the technical field of inhaled administration, which is composed of ascorbic acid and a diluent, and is in the form of a dry powder, wherein the weight percentage of the ascorbic acid is 10%-100%, and the weight percentage of the diluent is 0-90%; the dry powder aerosol realizes lung target delivery through inhaled administration, has good fluidity and lung deposition effect, and is mainly used for treating acute lung injury, and provides an efficient and safe treatment scheme for lung diseases.

Description

Technical Field

[0001] This invention relates to the field of inhalation drug delivery technology, specifically to an inhaled ascorbic acid powder inhaler and its preparation method. Background Technology

[0002] Acute lung injury (ALI) is a critical clinical disease characterized by diffuse inflammation of the lung parenchyma and refractory hypoxemia [1]. The main clinical manifestations are respiratory distress, pulmonary edema, impaired gas exchange, inflammation, hypoxemia and decreased lung compliance, which can progress to more serious acute respiratory distress syndrome (ARDS). The pathogenic factors of ALI / ARDS are divided into direct factors and indirect factors. Direct factors include pneumonia, gastric acid aspiration, drowning, severe lung infection, trauma, etc., which can directly cause alveolar lesions. Indirect factors include sepsis, shock, septicemia, trauma, acute pancreatitis, fat embolism and drug overdose, which first cause systemic inflammatory response, and then cause vascular endothelial damage, inflammatory cell infiltration and alveolar lesions. ALI / ARDS is more common in middle-aged and elderly people (60-85 years old), with a rapid onset and a mortality rate as high as 30% to 40%, which seriously threatens the life and quality of life of patients. While research on ALI / ARDS has made some progress, due to its complex etiology and pathogenesis, no drug or treatment can fundamentally cure ALI / ARDS. Current clinical treatments for ALI / ARDS include aggressive infection control, mechanical ventilation, oxygen therapy, and the use of glucocorticoid anti-inflammatory drugs such as dexamethasone and prednisolone. However, patients may experience muscle weakness and atrophy, osteoporosis, duodenal ulcers, and gastrointestinal discomfort during hormone therapy. Therefore, in-depth research into the pathogenesis of ALI / ARDS, the discovery of new drug targets, and the development of new, highly effective drugs are essential. Inflammatory and oxidative stress responses play important roles in ALI / ARDS; inhibiting these responses can alleviate the condition.

[0003] Ascorbic acid is a hydrophilic vitamin that must be obtained from the diet because the human body cannot synthesize it. This is due to a mutation in the gene responsible for synthesizing gluconolactone oxidase (the last enzyme in the ascorbic acid biosynthesis pathway). Ascorbic acid participates in various biochemical functions, including collagen synthesis and many other beneficial functions for critical illnesses, such as antioxidation, anti-inflammation, stimulation of norepinephrine secretion, promotion of angiotensin synthesis, anticoagulation, and immune regulation. Studies have shown that ascorbic acid has some therapeutic effect in treating acute lung injury. Research indicates that during periods of high physiological stress, doses of up to 8 g / day of ascorbic acid may be required. In fact, the National Institutes of Health (NIH) expert panel recommends a dose of 1.5 g / kg body weight, which is considered safe and does not produce significant harmful effects. However, oral administration cannot achieve such high plasma concentrations because high doses of oral ascorbic acid would saturate the intestinal absorption mechanism.

[0004] To overcome the limitations of oral administration of ascorbic acid, researchers have explored other routes of administration, among which inhalation is a promising method. Inhalation delivers the drug directly to the lungs through the respiratory tract. The drug is inhaled in the form of an aerosol, nebulizer, or dry powder and absorbed into the bloodstream through the alveolar epithelium. Inhalation offers the following advantages: Improved bioavailability: Inhalation bypasses the first-pass metabolism in the gastrointestinal tract and liver, allowing direct absorption through the lungs, significantly improving drug bioavailability. Rapid onset of action: Inhalation delivers the drug rapidly to the site of action, with a short onset time, suitable for relieving acute symptoms. Local treatment: For lung diseases, inhalation can directly act on the lesion site, increasing local drug concentration while reducing systemic side effects. Reduced dosage: Due to improved bioavailability, the required dosage can be reduced, lowering treatment costs and the risk of side effects. Therefore, preparing ascorbic acid into an inhalable powder form for the treatment of lung diseases such as acute lung injury has significant advantages and application prospects.

[0005] However, achieving inhaled administration of ascorbic acid presents significant formulation challenges. Ascorbic acid is a solid powder, and direct inhalation can cause respiratory irritation or discomfort, and dosage control is difficult. Therefore, it needs to be formulated into a powder inhaler suitable for inhalation, ensuring that the particle size, morphology, flowability, and stability of the powder inhaler meet the requirements for inhalation administration. Typically, the particle size of inhaled powder inhalers needs to be controlled within the range of 1-5 μm to ensure that the drug can deposit in the alveolar region deep within the lungs. Furthermore, the flowability of the powder inhaler is crucial for proper metering and the normal operation of the inhalation device.

[0006] In conclusion, the development of inhaled ascorbic acid powder can not only improve the bioavailability of ascorbic acid and reduce the dosage, but also act directly on the lungs to enhance the therapeutic effect, thus having important clinical application value. Summary of the Invention

[0007] To address the challenges of oral ascorbic acid administration, such as difficulty in targeting the lungs, high required dosage, and poor formulation flowability, this invention provides an inhaled ascorbic acid powder inhaler and its preparation method. This inhaled ascorbic acid powder inhaler, through a specific preparation process, produces ascorbic acid in μm-sized dry powder particles with a particle size D90 of less than 20 μm, preferably less than 10 μm, and more preferably less than 5 μm, suitable for inhalation administration. The preparation method includes steps such as pulverizing the ascorbic acid raw material, mixing with excipients, and spheroidizing to obtain highly spherical particles, improving the powder's flowability and dispersibility. This powder inhaler can be directly absorbed through the lungs, significantly improving the bioavailability of ascorbic acid, reducing the dosage, and targeting the lungs, making it particularly suitable for treating lung diseases. The preparation method of this invention successfully solves the technical challenges of inhaled ascorbic acid administration, providing a new treatment approach for clinical application.

[0008] To solve the above-mentioned technical problems, the present invention provides the following technical solution: an inhaled ascorbic acid powder spray, composed of ascorbic acid and a diluent, in the form of a dry powder, wherein the weight percentage of the ascorbic acid is 10%-100% and the weight percentage of the diluent is 0-90%.

[0009] As a preferred embodiment of the inhaled ascorbic acid powder mist of the present invention, wherein: the weight percentage of ascorbic acid is 40%-80%, and the weight percentage of the diluent is 20%-60%.

[0010] In a preferred embodiment of the inhaled ascorbic acid powder aerosol of the present invention, the ascorbic acid has a particle size of D90 < 20 μm, and the diluent has a particle size of 5 μm. <D90<20μm。

[0011] In a preferred embodiment of the inhaled ascorbic acid powder aerosol of the present invention, the ascorbic acid has a particle size of D90 < 10 μm, and the diluent has a particle size of 5 μm. <D90<10μm。

[0012] In a preferred embodiment of the inhaled ascorbic acid powder aerosol of the present invention, the ascorbic acid has a particle size of D90 < 5 μm, and the diluent has a particle size of 5 μm. <D90<10μm。

[0013] As a preferred embodiment of the inhaled ascorbic acid powder mist of the present invention, wherein the diluent is selected from lactose monohydrate, anhydrous lactose, mannitol, sucrose or trehalose.

[0014] As a preferred embodiment of the inhaled ascorbic acid powder mist of the present invention, wherein the diluent is lactose monohydrate or mannitol.

[0015] A method for preparing an inhaled ascorbic acid powder spray includes the following steps:

[0016] 1. Crush the ascorbic acid and diluent;

[0017] 2. Mix the pulverized ascorbic acid and diluent in a certain proportion to obtain a mixture;

[0018] 3. The mixture obtained in step 2 is sieved to obtain agglomerates;

[0019] 4. The agglomerates obtained in step 3 are spheroidized in a spheroidizing disk to prepare spherical particles;

[0020] 5. The spherical particles prepared in step 4 are quantitatively loaded into the inhaler.

[0021] As a preferred embodiment of the preparation method of the inhaled ascorbic acid powder atomizer of the present invention, wherein: the mesh size of the sieve in step 3 is 200-500μm, the spheroidizing speed in step 4 is 5-50rpm, and the angle between the bottom surface of the spheroidizing disk and the horizontal plane is between 15-45°.

[0022] As a preferred embodiment of the preparation method of the inhaled ascorbic acid powder atomizer of the present invention, wherein: the pulverizing equipment in step 1 is selected from ball mill, disc air jet mill, hammer mill, nail disc mill or fluidized bed air jet mill, and the mixing equipment in step 2 is selected from high shear mixer, planetary mixer, trough mixer, resonant mixer or air jet mixer.

[0023] Compared with existing technologies, the beneficial effects achieved by this invention are as follows: Significantly improved bioavailability: Through inhalation, the ascorbic acid powder aerosol of this invention can be directly absorbed through the lungs, avoiding the first-pass metabolism of the gastrointestinal tract and liver as with oral administration. This invention achieves higher blood drug concentrations with lower doses through efficient pulmonary absorption, thereby significantly improving the bioavailability of ascorbic acid and enhancing therapeutic efficacy. Targeted delivery to the lungs: This invention precisely delivers ascorbic acid to the lungs, allowing the drug to accumulate locally at the site of lung lesions. This targeted delivery method not only increases the local drug concentration in the lungs, enhancing the therapeutic effect on lung diseases, but also reduces the distribution of the drug throughout the body, thereby reducing the risk of systemic side effects. This characteristic is particularly suitable for lung diseases requiring local treatment. Excellent flowability: This invention uses a spheroidization process to prepare ascorbic acid particles, giving them high sphericity, significantly improving flowability compared to untreated ascorbic acid powder. Good flowability makes the particles easier to quantitatively fill and handle, ensuring dosage accuracy and consistency. This not only improves production efficiency but also ensures product quality, facilitating subsequent industrial production. Suitable particle size distribution: Through precise control of the preparation process, this invention ensures that the particle size D90 of ascorbic acid particles is less than 20 μm, preferably less than 10 μm, and more preferably less than 5 μm. This particle size range allows drug particles to effectively deposit in the alveolar region deep within the lungs, achieving optimal absorption and local therapeutic effects. Compared to traditional formulations, the particle size design of this invention significantly improves the accuracy and efficiency of drug delivery. Good dispersibility and stability: This invention incorporates surfactants into the formulation, effectively improving the dispersibility of ascorbic acid powder, preventing particle agglomeration, and ensuring the stability of the formulation. Excellent dispersibility allows the powder atomized uniformly during inhalation, avoiding a decrease in delivery efficiency due to particle aggregation, thereby ensuring effective drug deposition and absorption in the lungs. Reduced side effects: Because inhaled administration can achieve higher local drug concentrations at lower doses, this invention significantly reduces systemic side effects, such as gastrointestinal discomfort, compared to traditional oral administration. This improves patient safety and tolerability, which is especially important for patients on long-term medication. Easy to use and improves compliance: The inhaled ascorbic acid powder inhaler of this invention is in the form of a dry powder inhaler, which patients can administer themselves using a portable inhalation device without the need for assistance from professional medical personnel. Compared to injection or other complex administration methods, this non-invasive procedure is simpler and helps improve patient compliance, thereby improving treatment outcomes.

[0024] In summary, the inhaled ascorbic acid powder aerosol of this invention, through innovative preparation process and inhalation administration route, successfully overcomes the limitations of traditional oral ascorbic acid, such as low bioavailability, poor targeting, and insufficient formulation flowability. This invention achieves efficient delivery, targeted therapy, and improved safety of ascorbic acid, providing a novel solution for the treatment of lung diseases such as acute lung injury, and has significant clinical application value and broad market prospects. Attached Figure Description

[0025] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings:

[0026] Figure 1 This is a flowchart illustrating the preparation process of the inhaled ascorbic acid powder aerosol of the present invention;

[0027] Figure 2 This is a particle distribution diagram of the finished product tested in vitro according to the present invention;

[0028] Figure 3 This is an image of an animal tissue section from Embodiment 3 of the present invention;

[0029] Figure 4 This refers to the HE staining lung injury score of the animal in Example 3 of this invention;

[0030] Figure 5 These are the oxidative stress and lung inflammation indicators of the animals in Example 3 of this invention;

[0031] Figure 6 This is an image of an animal tissue section from Embodiment 4 of the present invention;

[0032] Figure 7 This is the HE staining lung injury score of the animal in Example 4 of this invention;

[0033] Figure 8 This shows the distribution of ascorbic acid in the animal tissue of Example 4 of the present invention. Detailed Implementation

[0034] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] The present invention provides a technical solution: an inhaled ascorbic acid powder aerosol and its preparation method, which is composed of ascorbic acid and a diluent, and the dosage form is a dry powder, wherein the weight percentage of the ascorbic acid is 10%-100% and the weight percentage of the diluent is 0-90%.

[0036] The ascorbic acid has a weight percentage of 40%–80%, and the diluent has a weight percentage of 20%–60%.

[0037] The ascorbic acid has a particle size of D90 < 20 μm, and the diluent has a particle size of 5 μm. <D90<20μm。

[0038] The ascorbic acid has a particle size of D90 < 10 μm, and the diluent has a particle size of 5 μm. <D90<10μm。

[0039] The ascorbic acid has a particle size of D90 < 5 μm, and the diluent has a particle size of 5 μm. <D90<10μm。

[0040] The diluent is selected from lactose monohydrate, anhydrous lactose, mannitol, sucrose, or trehalose.

[0041] The diluent is lactose monohydrate or mannitol.

[0042] like Figures 1-8 As shown, a method for preparing an inhaled ascorbic acid powder spray includes the following steps:

[0043] 1. Crush the ascorbic acid and diluent;

[0044] 2. Mix the pulverized ascorbic acid and diluent in a certain proportion to obtain a mixture;

[0045] 3. The mixture obtained in step 2 is sieved to obtain agglomerates;

[0046] 4. The agglomerates obtained in step 3 are spheroidized in a spheroidizing disk to prepare spherical particles;

[0047] 5. The spherical particles prepared in step 4 are quantitatively loaded into the inhaler.

[0048] In step 3, the mesh size of the sieve is 200-500μm, and in step 4, the spheroidizing speed is 5-50rpm, wherein the angle between the bottom surface of the spheroidizing disk and the horizontal plane is between 15-45°.

[0049] The equipment used for pulverizing in step 1 is selected from ball mill, disc jet mill, hammer mill, nail disc mill or fluidized bed jet mill, and the equipment used for mixing in step 2 is selected from high shear mixer, planetary mixer, trough mixer, resonant mixer or air jet mixer.

[0050] In addition, combined Figure 1 The image shows a flow chart illustrating the preparation process of an inhaled ascorbic acid powder spray. The specific steps are as follows:

[0051] Micronization:

[0052] The ascorbic acid and diluent are micronized separately to reduce the particle size of the raw materials to the target range (e.g., D90 < 20 μm) to meet the requirements for inhalation administration.

[0053] mix:

[0054] The micronized ascorbic acid is mixed with a diluent, and a mixture is obtained by uniform mixing. This step ensures the uniform distribution of each component.

[0055] Spherical polymerization:

[0056] The mixture is fed into a spheroidizing device for spheroidization treatment to form highly spherical particles. This step improves the flowability and dispersibility of the particles.

[0057] Filling:

[0058] The aggregated granules are quantitatively loaded into the inhalation device to ensure the accuracy and consistency of each dose.

[0059] Finished product:

[0060] The final product is an inhaled ascorbic acid powder spray, which can be used to treat lung diseases such as acute lung injury.

[0061] The flowchart clearly illustrates the key steps from raw material processing to finished product preparation, demonstrating the systematic and standardized nature of the formulation process. Example 1

[0062] Take 500g of ascorbic acid and 500g of lactose monohydrate.

[0063] Step 1: Use a disc-type air jet mill to grind ascorbic acid and lactose monohydrate to a particle size D90 of 3μm and 8μm respectively.

[0064] Step 2: Add the pulverized ascorbic acid and lactose monohydrate to a high-shear mixer and mix for 10 minutes to obtain a homogeneous mixture.

[0065] Step 3: Sieve the mixture through a sieve with a pore size of 300 μm to obtain agglomerates.

[0066] Step 4: Place the agglomerates in a spheroidizing dish, rotate at 30 rpm, with the bottom surface at a 30° angle to the horizontal plane, and spheroidize for 20 minutes to prepare spherical particles.

[0067] Step 5: Quantitatively fill the spherical particles into the dry powder inhaler, each dose containing 10mg of ascorbic acid.

[0068] The table below shows the relationship between the bulk density of the material and the angle of repose:

[0069]

[0070] The following table shows the particle distribution data from the in vitro testing of the finished product:

[0071]

[0072] Where: FPF: fine particle fraction (FPF)

[0073] MMAD: Mass Median aerodynamic diameter

[0074] GSD: Geometric standard deviation Example 2

[0075] Take 600g of ascorbic acid and 400g of mannitol.

[0076] Step 1: Use a fluidized bed jet mill to pulverize ascorbic acid and mannitol to a particle size D90 of 4μm and 7μm, respectively.

[0077] Step 2: Add the pulverized ascorbic acid and mannitol to a planetary mixer and mix for 15 minutes to obtain a homogeneous mixture.

[0078] Step 3: Sieve the mixture through a sieve with a pore size of 400 μm to obtain agglomerates.

[0079] Step 4: Place the agglomerates in a spheroidizing dish, rotate at 40 rpm, with the bottom surface at a 25° angle to the horizontal plane, and spheroidize for 15 minutes to prepare spherical particles.

[0080] Step 5: Quantitatively fill the spherical particles into the dry powder inhaler, each dose containing 15mg of ascorbic acid. Example 3

[0081] Eighteen healthy SPF-grade Sprague-Dawley (SD) rats were selected, half male and half female. Males weighed between 235.2 g and 266.1 g, while females weighed between 205.0 g and 231.5 g. Rats were randomly divided into three groups based on sex and weight: Normal group, Model group (LPS 10 mg / kg), and Inhaled Vitamin C intervention groups (VC-1h, VC-3h, VC-6h), with three animals of each sex in each group. All surviving animals were euthanized by intramuscular injection of Servetin 50, and death was ensured by exsanguination via the abdominal aorta / vein. A complete gross anatomical examination was then performed. Example 4

[0082] Twenty-four healthy SPF-grade Sprague-Dawley (SD) rats were selected, half male and half female. Males weighed between 231.4 g and 274.1 g, while females weighed between 212.3 g and 229.1 g. Rats were randomly assigned to four groups based on sex and weight: a normal group, a model group (LPS 15 mg / kg), an inhaled vitamin C intervention group (vitamin C 1 h), and an intravenous vitamin C intervention group (vitamin C iv 1000 mg / kg). Three animals of each sex were assigned to each group. All surviving animals were euthanized by intramuscular injection of salbutamol (Zaryl 50), and death was ensured by exsanguination via the abdominal aorta / vein. A complete gross anatomical examination was performed.

[0083] In summary, this invention significantly improves bioavailability and reduces dosage. The inhaled ascorbic acid powder inhaler bypasses the gastrointestinal tract and liver, directly absorbing into the bloodstream via alveoli. Compared to oral administration, pulmonary absorption significantly enhances the effective utilization of ascorbic acid. Utilizing the large surface area of ​​the lungs, this invention improves absorption efficiency, potentially increasing blood drug concentrations several times over, laying the foundation for low-dose, high-efficiency treatment. This delivery method is particularly suitable for rapidly metabolized drugs, shortening onset time and facilitating the relief of acute pulmonary symptoms. It also achieves targeted delivery to the lungs, resulting in a high local concentration, making it particularly suitable for treating lung diseases such as acute lung injury. Compared to oral administration, targeted delivery reduces systemic drug distribution, lowers side effects such as gastrointestinal discomfort, and improves treatment safety and specificity. Finally, it reduces the required ascorbic acid dosage due to improved bioavailability and targeted delivery, while still achieving or exceeding the therapeutic effect of oral administration. Further benefits: Reduced dosage not only lowers treatment costs but also mitigates the potential toxic side effects of high-dose oral administration, such as the burden on the liver and kidneys, making it particularly suitable for patients undergoing long-term treatment. For example, each dose in the examples contains only 10-15 mg of ascorbic acid, demonstrating high efficacy compared to the commonly used oral doses of several hundred milligrams. Significantly improved flowability: Spherical particles prepared through a spheroidization process exhibit high sphericity and excellent flowability, facilitating quantitative filling and use in inhalation devices. Further benefits: Spherical particles reduce inter-particle friction and agglomeration tendency. Compared to irregular particles, they have a smaller flow angle and shorter flow time, ensuring dosage consistency and production efficiency. This characteristic is particularly crucial in industrial production, reducing equipment clogging, improving filling accuracy, and providing technical support for large-scale production. Optimized particle size distribution: The ascorbic acid particle size D90 is controlled to be less than 20 μm (preferably less than 5 μm), ensuring effective drug deposition in the alveolar region. Further Explanation: A particle size of 1-5 μm is the optimal range for deep lung deposition. This invention precisely controls the particle size distribution through micronization and spheroidization processes, avoiding the deposition of large particles in the upper respiratory tract or the loss of small particles with exhalation. The particle size design of the diluent (5-20 μm) further optimizes the overall performance of the formulation, balancing dispersibility and stability. Enhanced Dispersibility and Stability: The addition of a diluent to the formulation, along with the spheroidization process, improves the dispersibility and stability of the powder, preventing particle agglomeration. Further Explanation: Good dispersibility ensures uniform atomization of the powder inhaler during inhalation, avoiding decreased delivery efficiency due to agglomeration, thereby increasing the lung deposition rate. Improved stability extends the shelf life of the formulation and reduces performance degradation caused by environmental factors (such as humidity), laying the foundation for product commercialization. Improved Patient Compliance: The inhaled administration method is simple to operate, using a portable dry powder inhaler, allowing patients to self-administer the medication. The non-invasive design improves treatment compliance.Further, compared to oral tablets or injections, inhaled medication requires no swallowing or specialized operation, making it particularly suitable for elderly patients with swallowing difficulties or those unwilling to undergo injections. Its portability allows patients to take medication anytime, anywhere, at home or when out and about, enhancing the flexibility and continuity of treatment, which is especially beneficial for the management of chronic lung disease.

[0084] Clinical Application Prospects: The inhaled ascorbic acid powder aerosol of this invention is not only suitable for acute lung injury, but can also be extended to other lung diseases, such as chronic obstructive pulmonary disease (COPD), and even as adjuvant therapy for early-stage lung cancer. Its anti-inflammatory and antioxidant properties provide possibilities for multi-target therapy. Technological Innovation: The application of the spheroidization process is a major highlight of this invention, not only solving the problem of poor flowability of ascorbic acid powder, but also providing a reference for the development of inhaled formulations of other poorly soluble drugs. Market Potential: With the rising incidence of lung diseases and the increasing demand from patients for highly effective, low-side-effect treatments, this invention has broad market prospects, especially against the backdrop of the widespread use of portable inhalation devices.

[0085] Furthermore, in order to provide a concise description of exemplary embodiments, not all features of actual embodiments (i.e., those features that are not relevant to the best mode of carrying out the invention as currently considered, or those features that are not relevant to implementing the invention) may be omitted.

[0086] It should be understood that numerous specific implementation decisions can be made during the development of any practical implementation, such as in any engineering or design project. Such development efforts may be complex and time-consuming, but for those of ordinary skill in the art who benefit from this disclosure, the development effort will be a routine task in design, manufacturing, and production without requiring extensive experimentation.

[0087] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. An inhaled ascorbic acid powder spray, characterized in that, It is composed of ascorbic acid and a diluent, and is in the form of a dry powder. The weight percentage of the ascorbic acid is 10%-100%, and the weight percentage of the diluent is 0-90%.

2. The inhaled ascorbic acid powder spray according to claim 1, characterized in that: The ascorbic acid has a weight percentage of 40%–80%, and the diluent has a weight percentage of 20%–60%.

3. The inhaled ascorbic acid powder spray according to claim 2, characterized in that: The ascorbic acid has a particle size of D90 < 20 μm, and the diluent has a particle size of 5 μm. <D90<20μm。 4. The inhaled ascorbic acid powder aerosol according to claim 3, characterized in that: The ascorbic acid has a particle size of D90 < 10 μm, and the diluent has a particle size of 5 μm. <D90<10μm。 5. The inhaled ascorbic acid powder aerosol according to claim 4, characterized in that: The ascorbic acid has a particle size of D90 < 5 μm, and the diluent has a particle size of 5 μm. <D90<10μm。 6. The inhaled ascorbic acid powder aerosol according to claim 5, characterized in that: The diluent is selected from lactose monohydrate, anhydrous lactose, mannitol, sucrose, or trehalose.

7. The inhaled ascorbic acid powder aerosol according to claim 6, characterized in that: The diluent is lactose monohydrate or mannitol.

8. The method for preparing the inhaled ascorbic acid powder inhaler according to any one of claims 1-7, characterized in that: Includes the following steps:

1. Crush the ascorbic acid and diluent; 2. Mix the pulverized ascorbic acid and diluent in a certain proportion to obtain a mixture; 3. The mixture obtained in step 2 is sieved to obtain agglomerates; 4. The agglomerates obtained in step 3 are spheroidized in a spheroidizing disk to prepare spherical particles; 5. The spherical particles prepared in step 4 are quantitatively loaded into the inhaler.

9. The method for preparing the inhaled ascorbic acid powder aerosol according to claim 8, characterized in that: In step 3, the mesh size of the sieve is 200-500μm, and in step 4, the spheroidizing speed is 5-50rpm, wherein the angle between the bottom surface of the spheroidizing disk and the horizontal plane is between 15-45°.

10. The method for preparing the inhaled ascorbic acid powder aerosol according to claim 8, characterized in that: The equipment used for pulverizing in step 1 is selected from ball mill, disc jet mill, hammer mill, nail disc mill or fluidized bed jet mill, and the equipment used for mixing in step 2 is selected from high shear mixer, planetary mixer, trough mixer, resonant mixer or air jet mixer.

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