A nose spray of azelastine hydrochloride and its preparation method and application

Abstract

The application belongs to the technical field of pharmaceutical preparations, and relates to a nose spray of azelastine hydrochloride and a preparation method and application thereof. The nose spray of azelastine hydrochloride is composed of the following raw materials in parts by weight: azelastine hydrochloride 0.10%-0.15%, quercetin 0.005%-0.025%, absorption promoter 0.1%-0.25%, cosolvent 5.0%-6.5%, thickening agent 0.10%-0.5%, osmotic pressure regulator 0.85%-0.90%, pH regulator, preservative 0.10%-0.30%, and purified water added to 100%; and the pH of the phosphate buffer salt regulating system is 6.75-6.90. The application creatively combines azelastine hydrochloride and quercetin, and the two active components produce obvious synergistic pharmacological effects after being combined, can effectively reduce the required dose of azelastine hydrochloride used alone, can significantly reduce the bitter taste, peculiar smell and other uncomfortable reactions caused by azelastine hydrochloride itself, and greatly improves the drug compliance of patients.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, and relates to a zavastin hydrochloride nasal spray, its preparation method, and its application. Background Technology

[0002] Allergic rhinitis is a disease characterized by a specific inflammatory response in the nasal mucosa, closely related to IgE-mediated mediators (mainly histamine) and various immune-active cells and cytokines. Currently, treatment for allergic rhinitis primarily relies on comprehensive drug therapy, including corticosteroids (nasal or oral), nasal decongestants (such as oxymetazoline nasal spray), mast cell membrane stabilizers (such as sodium cromoglycate), and H1 receptor antagonists (such as antihistamines), which can rapidly improve patient symptoms in a short period.

[0003] Azelastine hydrochloride, also known as 4-(4-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azelazone-4-yl)-1-(2H)-phthalazine hydrochloride, is an antihistamine, a long-acting anti-allergic drug with a half-life of 16 hours. It not only antagonizes histamine H1 receptors but also has anti-inflammatory effects; even small oral doses can significantly inhibit and antagonize the production and release of inflammatory mediators such as leukotrienes and histamine. Azelastine hydrochloride tablets were first developed by Asta-Werke AG in Germany and launched in Japan in 1986. Subsequently, it was marketed in more than 10 countries, including Germany and the UK, for the treatment of allergic diseases. Azelastine hydrochloride tablets have a distinctly bitter taste after absorption through the digestive tract, causing significant oral discomfort during use, making it difficult for patients to accept and resulting in low treatment adherence. Due to the problem of poor medication adherence caused by the strong bitter taste of azelastine hydrochloride when taken orally, a nasal spray of azelastine hydrochloride was developed. The nasal spray of azelastine hydrochloride delivers the drug directly to the nasal cavity through local administration, thereby fundamentally avoiding the bitter taste caused by the drug dissolving in the mouth.

[0004] Chinese patent CN201711218505.5 discloses a nasal composition containing azelastine hydrochloride, comprising: azelastine or its pharmaceutical salt, glucocorticoids, and other excipients. 100 ml of this composition contains: 0.05-5 g of azelastine or its pharmaceutical salt and 0.1-2 g of glucocorticoids. This patent primarily addresses the combined anti-allergic effect, rapid onset of action, and reduction of side effects associated with single-hormone therapy.

[0005] Chinese patent CN202510332389.8 discloses an azelastine hydrochloride nasal spray and its preparation method. The azelastine hydrochloride nasal spray, by mass percentage, comprises the following components: 0.1% azelastine hydrochloride, 0.3-0.4% chamomile-houttuynia cordata-peony flower composite water-extracted fermented product, 0.005-0.01% stabilizer, 0.002-0.01% preservative, 0.95-1.05% thickener, 0.7-0.8% pH adjuster, 0.45-0.48% sodium chloride, and the balance being purified water. The prepared azelastine hydrochloride nasal spray effectively reduces eye irritation during use, ensuring safer and more reliable use.

[0006] Azelastine hydrochloride nasal spray, as a long-acting anti-allergy compound, demonstrates unique advantages in treating allergic rhinitis. This medication not only effectively blocks histamine secretion, reducing the occurrence of allergic reactions, but also does not interfere with the body's normal physiological processes. More importantly, azelastine hydrochloride nasal spray can act directly on the lesion site within the nasal cavity, bypassing the systemic circulation and metabolism process, thus achieving a faster and more direct effect. Patients can quickly experience symptom relief after use, thereby improving the immediate effectiveness of treatment, making this medication an ideal choice for treating allergic rhinitis. However, azelastine hydrochloride nasal spray is primarily used to relieve symptoms during allergic rhinitis attacks; long-term use may lead to adverse reactions such as nosebleeds and drowsiness.

[0007] Therefore, developing a new generation of highly effective and low-toxicity azelastine hydrochloride nasal spray, with the aim of improving efficacy while reducing the incidence of adverse reactions, has significant clinical value and translational significance. Summary of the Invention

[0008] Therefore, the purpose of this invention is to provide a azelastine hydrochloride nasal spray and its preparation method. The final azelastine hydrochloride nasal spray, in which azelastine hydrochloride and quercetin are used in combination, exhibits a significant synergistic effect, which can significantly enhance the therapeutic effect on allergic rhinitis. This is of great significance for the development of highly effective and safe drugs for the treatment of allergic rhinitis.

[0009] The object of this invention is achieved in the following manner:

[0010] A azelastine hydrochloride nasal spray, comprising the following raw materials in parts by weight: azelastine hydrochloride 0.10%-0.15%, quercetin 0.005%-0.025%, absorption promoter 0.1%-0.25%, solubilizer 5.0%-6.5%, thickener 0.10%-0.5%, osmotic pressure regulator 0.85%-0.90%, pH adjuster as needed, preservative 0.10%-0.30%, and purified water to 100%; the pH of the system is adjusted to 6.75-6.90 using phosphate buffer.

[0011] Preferably, the absorption enhancer is dodecyl-β-D-maltodextrin.

[0012] Preferably, the cosolvent is 1,2-propanediol.

[0013] Preferably, the thickener is polyvinylpyrrolidone.

[0014] Preferably, the osmotic pressure regulator is sodium chloride.

[0015] Preferably, the pH adjuster is sodium dihydrogen phosphate and disodium hydrogen phosphate.

[0016] Preferably, the preservative is potassium sorbate.

[0017] The preparation method of the azithromycin hydrochloride nasal spray is as follows: Dissolve the pH adjuster in purified water, and add the osmotic pressure adjuster, preservative, solubilizer, and absorption promoter in sequence and mix well; add azithromycin hydrochloride, stir to dissolve, add quercetin, and stir until the solution is clear; add the thickener in portions and stir to swell, then add purified water to a final volume of 100g and adjust the pH; let stand, filter with a filter membrane for sterilization, and aseptically fill and seal to obtain the azithromycin hydrochloride nasal spray.

[0018] Preferably, the preparation method includes the following steps: dissolving sodium dihydrogen phosphate and disodium hydrogen phosphate in purified water, then sequentially adding sodium chloride, potassium sorbate, 1,2-propanediol, and dodecyl-β-D-maltodextrin and mixing well; adding azithromycin hydrochloride, stirring to dissolve, then adding quercetin, and maintaining the temperature at 40-45℃ while stirring until the solution is clear; adding polyvinylpyrrolidone K90 in portions while stirring to swell, then adjusting the volume with purified water to 100g, controlling the pH to 6.75-6.90; allowing to stand, filtering with a 0.22μm filter membrane for sterilization, and aseptically filling and sealing to obtain azithromycin hydrochloride nasal spray.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] This invention provides a nasal spray containing azelastine hydrochloride and quercetin, which has excellent formulation stability, low irritation to the nasal mucosa, and better medication safety.

[0021] This invention creatively combines azelastine hydrochloride with quercetin, and the combination of the two active ingredients produces a significant synergistic pharmacological effect, which can effectively reduce the dosage required for azelastine hydrochloride alone. The reduced dosage can significantly alleviate the adverse reactions such as bitter taste and off-flavor caused by azelastine hydrochloride itself, and greatly improve patient medication compliance.

[0022] The azelastine hydrochloride nasal spray prepared by this invention exhibits significantly superior efficacy compared to commercially available control products in the treatment of allergic rhinitis. When used in combination with other nasal sprays for allergic rhinitis intervention, the overall therapeutic effect is significantly better, and the onset of action is faster. This advantage is achieved through the unique synergistic formulation of this invention, providing clinical patients with a more efficient medication option. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. 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 this application.

[0024] The following description is further illustrated with specific embodiments and comparative examples. Unless otherwise specified, the raw materials involved in the following specific embodiments and comparative examples are all commercially available. Unless otherwise specified, the instruments used are all commercially available. Unless otherwise specified, the processes involved are conventionally selected by those skilled in the art.

[0025] Example 1

[0026] A zavastin hydrochloride nasal spray and its preparation method are as follows:

[0027]

[0028] Sodium dihydrogen phosphate and disodium hydrogen phosphate were dissolved in purified water. Sodium chloride, potassium sorbate, 1,2-propanediol, and dodecyl-β-D-maltodextrin were added sequentially and mixed well. Azafiltrate hydrochloride was added and stirred to dissolve. Quercetin was then added and kept at a constant temperature of 42°C with stirring until the solution became clear. Polyvinylpyrrolidone K90 was added in portions and stirred until swollen. The volume was adjusted to 100g with purified water, and the pH of the system was precisely adjusted to 6.82. The solution was allowed to stand, filtered through a 0.22μm filter membrane for sterilization, and then aseptically filled and sealed to obtain azafiltrate hydrochloride quercetin nasal spray.

[0029] Example 2

[0030] A zavastin hydrochloride nasal spray and its preparation method are as follows:

[0031]

[0032] Sodium dihydrogen phosphate and disodium hydrogen phosphate were dissolved in purified water. Sodium chloride, potassium sorbate, 1,2-propanediol, and dodecyl-β-D-maltodextrin were added sequentially and mixed well. Azafiltrate hydrochloride was added and stirred to dissolve. Quercetin was then added and the mixture was kept warm and stirred at 45°C until the solution became clear. Polyvinylpyrrolidone K90 was added in portions and stirred until swollen. The volume was adjusted to 100g with purified water, and the pH of the system was adjusted to 6.90. The solution was allowed to stand, filtered through a 0.22μm filter membrane for sterilization, and then aseptically filled and sealed to obtain azafiltrate hydrochloride quercetin nasal spray.

[0033] Example 3

[0034] A zavastin hydrochloride nasal spray and its preparation method are as follows:

[0035]

[0036] Sodium dihydrogen phosphate and disodium hydrogen phosphate were dissolved in purified water. Sodium chloride, potassium sorbate, 1,2-propanediol, and dodecyl-β-D-maltodextrin were added sequentially and mixed well. Azafiltrate hydrochloride was added and stirred to dissolve. Quercetin was then added and the mixture was kept warm and stirred at 40°C until the solution became clear. Polyvinylpyrrolidone K90 was added in portions and stirred until swollen. The volume was adjusted to 100g with purified water, and the pH of the system was adjusted to 6.75. The solution was allowed to stand, filtered through a 0.22μm filter membrane for sterilization, and then aseptically filled and sealed to obtain azafiltrate hydrochloride quercetin nasal spray.

[0037] Example 4

[0038] A zavastin hydrochloride nasal spray and its preparation method are as follows:

[0039]

[0040] Sodium dihydrogen phosphate and disodium hydrogen phosphate were dissolved in purified water. Sodium chloride, potassium sorbate, 1,2-propanediol, and dodecyl-β-D-maltodextrin were added sequentially and mixed well. Azafiltrate hydrochloride was added and stirred to dissolve. Quercetin was then added and the mixture was kept warm and stirred at 45°C until the solution became clear. Polyvinylpyrrolidone K90 was added in portions and stirred until swollen. The volume was adjusted to 100g with purified water, and the pH of the system was adjusted to 6.75. The solution was allowed to stand, filtered through a 0.22μm filter membrane for sterilization, and then aseptically filled and sealed to obtain azafiltrate hydrochloride quercetin nasal spray.

[0041] Example 5

[0042] A zavastin hydrochloride nasal spray and its preparation method are as follows:

[0043]

[0044] Sodium dihydrogen phosphate and disodium hydrogen phosphate were dissolved in purified water. Sodium chloride, potassium sorbate, 1,2-propanediol, and dodecyl-β-D-maltodextrin were added sequentially and mixed well. Azafiltrate hydrochloride was added and stirred to dissolve. Quercetin was then added and the mixture was kept warm and stirred at 40°C until the solution became clear. Polyvinylpyrrolidone K90 was added in portions and stirred until swollen. The volume was adjusted to 100g with purified water, and the pH of the system was adjusted to 6.90. The solution was allowed to stand, filtered through a 0.22μm filter membrane for sterilization, and then aseptically filled and sealed to obtain azafiltrate hydrochloride quercetin nasal spray.

[0045] Example 6

[0046] A zavastin hydrochloride nasal spray and its preparation method are as follows:

[0047]

[0048] Sodium dihydrogen phosphate and disodium hydrogen phosphate were dissolved in purified water. Sodium chloride, potassium sorbate, 1,2-propanediol, and dodecyl-β-D-maltodextrin were added sequentially and mixed well. Azafiltrate hydrochloride was added and stirred to dissolve. Quercetin was then added and the mixture was kept warm and stirred at 42°C until the solution became clear. Polyvinylpyrrolidone K90 was added in portions and stirred until swollen. The volume was adjusted to 100g with purified water, and the pH of the system was adjusted to 6.82. The solution was allowed to stand, filtered through a 0.22μm filter membrane for sterilization, and then aseptically filled and sealed to obtain azafiltrate hydrochloride quercetin nasal spray.

[0049] Comparative Example 1

[0050] The difference from Example 1 is that it does not contain quercetin.

[0051]

[0052] Comparative Example 2

[0053] The difference from Example 1 is that it does not contain azithromycin hydrochloride.

[0054]

[0055] Comparative Example 3

[0056] The difference from Example 1 is that the cosolvent 1,2-propanediol is replaced with glycerol.

[0057]

[0058] Comparative Example 4

[0059] The difference from Example 1 is that the thickener polyvinylpyrrolidone K90 is replaced with hydroxypropyl methylcellulose (HPMCK4M).

[0060]

[0061] Comparative Example 5

[0062] The difference from Example 1 is that the absorption enhancer dodecyl-β-D-maltodextrin is replaced with Tween 80.

[0063]

[0064] Comparative Example 6

[0065] The difference from Example 1 is that the amount of quercetin is increased.

[0066]

[0067] Stability test

[0068] Accelerated stability studies were conducted on the nasal sprays prepared in Examples 1-6 of this invention. The sprays were stored at 40℃±2℃ and RH 75%±5% for 6 months, and samples were taken for testing at each 6-month mark. The appearance, clarity, pH, and spray characteristics of the samples were tested. The contents of azelastine hydrochloride and quercetin, as well as related substances, were determined according to pharmacopoeia methods.

[0069] Detection of azithromycin hydrochloride content and related substances

[0070] Mobile phase: acetonitrile-0.1% phosphoric acid aqueous solution (40:60, V / V). Accurately pipette an appropriate amount of the drug solution and dilute it with the mobile phase to prepare the test solution; separately prepare a reference solution of azelastine hydrochloride using the same method, inject the solutions separately, and calculate the percentage content of azelastine hydrochloride using the external standard method.

[0071] Determination of related substances: Take the chromatogram of the test solution after injection, record the total area of ​​all impurity peaks other than the retention time of the main peak, and calculate the total content of related substances and the content of the single largest impurity using the peak area normalization method.

[0072] Detection of quercetin content and related substances

[0073] Mobile phase: methanol-0.2% phosphoric acid aqueous solution (55:45, V / V). Accurately pipette an appropriate amount of the drug solution, dilute with methanol to the mark, sonicate to break the emulsion, centrifuge, and collect the supernatant as the test solution; separately prepare a reference solution using quercetin reference standard, and perform HPLC analysis to detect the quercetin content. Calculate the percentage content of quercetin using the external standard method.

[0074] Determination of related substances: Record the chromatogram, subtract the solvent peak, and calculate the increase of quercetin oxidative degradation impurities and total related substances using the peak area normalization method.

[0075] Table 1. Stability test results

[0076]

[0077] As shown in Table 1 above, the samples of Examples 1-6 of the present invention exhibit excellent performance in all aspects, with Example 1 showing the best overall stability. In contrast, Comparative Examples 1-6, which do not contain core functional components, replace excipients, or increase the amount of quercetin, suffer from problems such as changes in properties, decreased pH stability, significant degradation of active ingredients, and increased levels of related substances, resulting in significantly weaker overall stability compared to the examples of the present invention.

[0078] Stimulation test

[0079] To evaluate the irritation and safety of the nasal spray containing azithromycin hydrochloride of the present invention on the nasal mucosa, a bullfrog mucosal irritation model was used for safety investigation.

[0080] Healthy adult bullfrogs were selected and randomly divided into a blank control group, Example 1-3 groups, and Comparative Examples 1-6 groups, with 6 bullfrogs in each group. Before the experiment, the bullfrogs were kept still for 24 hours to ensure that their condition was stable and their body surface mucous membranes were intact and undamaged.

[0081] The skin and mucous membranes on the backs of bullfrogs in each group were cleaned with water and air-dried naturally. The blank control group received no treatment. The corresponding test preparation was evenly applied to the other groups once a day for 7 consecutive days. Mucosal congestion, edema, erosion, exudation, and pigmentation abnormalities were observed daily. At the end of the experiment, a mucosal irritation intensity scoring system was used for quantitative evaluation. The scoring system is as follows: 0 points (no irritation): The mucosa is intact and smooth, without congestion, edema, erosion, or abnormal secretions; 1 point (very mild irritation): The mucosa is slightly red, without edema or erosion; 2 points (mild irritation): The mucosa is significantly congested and slightly edematous, without erosion; 3 points (moderate irritation): The mucosa is severely congested and edematous, with mild erosion; 4 points (severe irritation): The mucosa is severely eroded, with a large amount of exudation and significant tissue damage.

[0082] After 7 days of continuous administration, individual mucosal irritation scores were performed on 6 bullfrogs in each group. All raw individual data were recorded, and the average scores of each group were calculated. The experimental data are shown in Table 2 below.

[0083] Table 2 Results of the Stimulation Test

[0084]

[0085] The experimental results showed that the average mucosal irritation score of the blank control group and groups 1-3 of the examples was 0.0. All experimental animals had good mucosal condition and no irritation damage, and the safety was excellent. The control groups 1-6 had mucosal irritation problems of varying degrees, with an average irritation score between 0.5 and 1.5. Some animals showed abnormalities such as mucosal dryness, congestion, and edema, and had very mild to mild mucosal irritation. The safety was significantly lower than that of the preparations in the examples of this invention.

[0086] Study on the effect of azelastine hydrochloride nasal spray on allergic rhinitis.

[0087] Eighty SD rats were randomly divided into 10 groups (n=8 per group): normal group, model group, Example 1 group, positive drug group, and comparative examples 1-6.

[0088] Except for the normal group, the remaining 10 groups of rats were used to establish an OVA-induced allergic rhinitis model.

[0089] Systemic sensitization phase: OVA 0.3mg + aluminum hydroxide 30mg, dissolved in 1mL of normal saline, injected intraperitoneally; administered every other day for 7 consecutive days (total 14 days). The normal group received an equal volume of normal saline intraperitoneally.

[0090] Local nasal provocation phase: On day 14 after the last intraperitoneal sensitization, rats were provoked by nasal instillation of 2% OVA saline solution, 50 μL per nostril, once daily for 7 consecutive days; the normal group received an equal volume of saline solution instilled into the nostrils. The appearance of typical allergic symptoms such as frequent sneezing, nose scratching, runny nose, and nasal itching after provocation indicated successful model establishment.

[0091] Administer medication starting the day after nasal stimulation, once daily at the same time, for 28 days.

[0092] Example 1 group: 50 μL of the nasal spray from Example 1 was administered to each nostril;

[0093] Positive drug group: 50 μL of commercially available azelastine hydrochloride nasal spray (Guizhou Yunfeng Pharmaceutical Co., Ltd.) was administered to each nasal cavity;

[0094] Comparative Examples 1-6: Each group was given a corresponding nasal spray, 50 μL per nostril.

[0095] Normal group and model group: Administer equal volume of physiological saline nasal drops, 50 μL per nasal cavity.

[0096] Thirty minutes after the last nasal instillation, the number of sneezes and the number of head scratches of the rats within 15 minutes were observed and recorded. The rats scratched their noses continuously with their hind paws until the paws were lowered to mark the number of times they scratched their noses.

[0097] Experimental results

[0098] The differences between groups were analyzed using the t-test, with p < 0.05 considered statistically significant. The specific results are shown in Table 3.

[0099] Table 3 Effects on allergic rhinitis model rats ( ±s, n=8)

[0100]

[0101] Compared with the normal group, ## p < 0.01; compared with the model group,* p < 0.05 ** p < 0.01.

[0102] Compared with Example 1, & p < 0.05 && p < 0.01.

[0103] Compared with the normal group, the number of sneezes in the model group rats was significantly increased, and the difference was statistically significant. Compared with the model group, the number of sneezes in the Example 1 group and the Comparative Examples 1-6 groups was significantly reduced. Compared with the Comparative Examples 1-6 groups, the number of sneezes in the Example 1 group was significantly reduced.

[0104] Compared with the normal group, the number of times rats in the model group scratched their noses was significantly increased, and the difference was statistically significant. Compared with the model group, the number of times rats in Example 1 and Comparative Examples 1-6 scratched their noses was significantly reduced. Compared with Comparative Examples 1-6, the number of times rats in Example 1 scratched their noses was significantly reduced.

[0105] Compared with the positive drug group, the number of sneezes and nose scratching in rats in Example 1 was significantly reduced, indicating that the azithromycin nasal spray of the present invention is significantly more effective than existing marketed formulations. Quercetin can exert a synergistic anti-allergic rhinitis effect with azithromycin hydrochloride.

[0106] Animal studies have shown that the azelastine hydrochloride nasal spray of this invention can significantly reduce sneezing and nasal scratching allergic behaviors in rats with allergic rhinitis, and effectively relieve typical allergic symptoms such as nasal itching and sneezing; and Example 1 has the best efficacy, significantly better than Comparative Examples 1-6. This demonstrates that the specific compound components and excipient formulation of this invention can improve the stability of the active ingredients and synergistically enhance the anti-allergic rhinitis efficacy of azelastine hydrochloride and quercetin.

[0107] The foregoing has only described certain exemplary embodiments of the present invention by way of illustration. Undoubtedly, those skilled in the art can modify the described embodiments in various ways without departing from the spirit and scope of the present invention. Therefore, the above description is illustrative in nature and should not be construed as limiting the scope of protection of the claims of the present invention.

Claims

1. A zavastin hydrochloride nasal spray, characterized in that, The azithromycin hydrochloride nasal spray is composed of the following raw materials in parts by weight: azithromycin hydrochloride 0.10%-0.15%, quercetin 0.005%-0.025%, absorption enhancer 0.1%-0.25%, solubilizer 5.0%-6.5%, thickener 0.10%-0.5%, osmotic pressure regulator 0.85%-0.90%, pH adjuster, preservative 0.10%-0.30%, and purified water to 100%; the pH of the system is adjusted to 6.75-6.90 using phosphate buffer.

2. The azithromycin hydrochloride nasal spray according to claim 1, characterized in that, The absorption enhancer is dodecyl-β-D-maltodextrin.

3. The azithromycin hydrochloride nasal spray according to claim 1, characterized in that, The cosolvent is 1,2-propanediol.

4. The azithromycin hydrochloride nasal spray according to claim 1, characterized in that, The thickener is polyvinylpyrrolidone.

5. The azithromycin hydrochloride nasal spray according to claim 1, characterized in that, The osmotic pressure regulator is sodium chloride.

6. The azithromycin hydrochloride nasal spray according to claim 1, characterized in that, The pH adjuster is sodium dihydrogen phosphate and disodium hydrogen phosphate.

7. The azithromycin hydrochloride nasal spray according to claim 1, characterized in that, The preservative is potassium sorbate.

8. The azithromycin hydrochloride nasal spray according to claim 1, characterized in that, The preparation method includes the following steps: Dissolve the pH adjuster in purified water, then add the osmotic pressure adjuster, preservative, solubilizer, and absorption promoter in sequence and mix well. Add azithromycin hydrochloride, stir to dissolve, then add quercetin and stir until the solution is clear. Add the thickener in portions and stir to dissolve. Adjust the volume with purified water to 100g and adjust the pH. Let stand, filter to remove bacteria, and aseptically fill and seal to obtain azithromycin hydrochloride nasal spray.

9. The azithromycin hydrochloride nasal spray according to claim 8, characterized in that, The preparation method includes the following steps: Sodium dihydrogen phosphate and disodium hydrogen phosphate are dissolved in purified water, and sodium chloride, potassium sorbate, 1,2-propanediol, and dodecyl-β-D-maltodextrin are added sequentially and mixed well; azirstin hydrochloride is added, stirred and dissolved, and then quercetin is added. The mixture is kept warm at 40-45℃ and stirred until the solution is clear; polyvinylpyrrolidone K90 is added in portions and stirred until swollen; purified water is added to a final volume of 100g, and the pH is controlled at 6.75-6.90; the mixture is allowed to stand, filtered through a 0.22μm filter membrane for sterilization, and then aseptically filled and sealed to obtain azirstin hydrochloride nasal spray.

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