Rhinitis spray for treating rhinitis and preparation method thereof

Abstract

The invention provides a rhinitis spray for treating rhinitis and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines. Folium artemisiae argyi, ginseng leaves, dandelion, herba schizonepetae, radix saposhnikoviae, radix scutellariae, flos magnoliae, menthol and borneol are used as traditional Chinese medicine raw materials, sulfobutyl-beta-cyclodextrin sodium and polysorbate-80 are added to prepare the spray, and the oil yield of the medicine, the utilization rate of the medicinal materials and the sterilization and bacteriostasis effects of the medicine are remarkably improved. The spray can be directly sprayed into the nose by means of a manual pump or gas pressure, can also be used for atomization treatment, does not need high-temperature extraction of medicine components, can be used for low-temperature atomization such as ultrasonic atomization or compression atomization, and reduces the pain of high-temperature fumigation; and the quality of the spray is stable and controllable.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a nasal spray for treating rhinitis and its preparation method. Background Technology

[0002] Rhinitis is an acute or chronic inflammation of the nasal mucosa or submucosal tissue caused by viral infection, bacterial infection, or irritant stimulation, leading to damage to the nasal mucosa or submucosal tissue. Rhinitis causes excessive mucus production, typically resulting in symptoms such as runny nose and nasal congestion. Traditional Chinese medicine prescriptions administered via nebulized inhalation have shown good efficacy in treating various types of rhinitis.

[0003] Existing technologies utilize steam generated by a nebulizer to extract volatile components from medicinal herbs. Patients inhale the steam, and the active ingredients are absorbed through the nasal mucosa, relieving nasal congestion and runny nose. This method is effective for treating various types of rhinitis. However, it has the following drawbacks in practical use: 1. High-temperature steam is required to extract the medicinal components, which can severely irritate the patient's eyes and skin, causing discomfort and prolonged treatment. 2. The steam generated is not concentrated enough and is easily affected by airflow, leading to diffusion and loss of medicinal components, thus affecting the treatment effect. 3. Residual liquid from the medicinal herbs can contaminate the nebulizer equipment, making it difficult to clean and shortening its lifespan over time. 4. Steam distillation cannot fully extract the effective components, resulting in resource waste. 5. Due to the use of traditional Chinese medicine in prescriptions, variations in herb ratios, herb quality, and equipment efficiency can lead to significant differences in the quality of the medication actually used by patients, making quality control difficult and affecting efficacy.

[0004] Therefore, adjusting the composition of traditional Chinese medicine and the method of drug extraction to improve the therapeutic effect of traditional Chinese medicine on rhinitis in nebulization therapy is a technical problem that needs to be solved. Summary of the Invention

[0005] In view of this, the present invention provides a nasal spray for treating rhinitis, comprising the following parts by weight of traditional Chinese medicine raw materials:

[0006] Artemisia argyi 50-60 parts, ginseng leaves 90-100 parts, dandelion 90-100 parts, schizonepeta tenuifolia 90-100 parts, saposhnikovia divaricata 50-60 parts, scutellaria baicalensis 50-60 parts, magnolia biondii 80-100 parts, menthol 3.5-4 parts, borneol 1.5-2 parts.

[0007] Preferably, the nasal spray for treating rhinitis also contains 10-30 parts of sodium sulfobutyl-β-cyclodextrin and 20-60 parts of polysorbate-80.

[0008] This invention also provides a method for preparing a nasal spray for treating rhinitis, comprising the following steps:

[0009] (1) Take Artemisia argyi leaves, ginseng leaves, dandelion, Schizonepeta tenuifolia, Saposhnikovia divaricata, Scutellaria baicalensis, and Magnolia biondii, and sift them to make coarse powder of medicinal materials;

[0010] (2) Water is added to the crude powder of the medicinal material for extraction, and the volatile oil layer and the aqueous layer are collected separately and mixed to obtain an oil-water mixture;

[0011] (3) Add sodium sulfobutyl-β-cyclodextrin and polysorbate-80 to the oil-water mixture, shake well until the solution is clear, and obtain the herbal extract;

[0012] (4) Take menthol and borneol, dissolve them in ethanol, mix them with the herbal extract, dilute with water to obtain the nasal spray.

[0013] Preferably, the sieve opening in step (1) is 20-25 mesh.

[0014] Preferably, the mass ratio of the crude medicinal powder and water in step (2) is 1:5 to 10.

[0015] Preferably, the extraction temperature in step (2) is 90-100℃.

[0016] Preferably, the volume ratio of the volatile oil layer to the water layer in the oil-water mixture in step (2) is 1-10:90-99.

[0017] Preferably, the oil-water mixture in step (2) is collected at a rate of 100-110 mL per 550-600 g of crude medicinal powder.

[0018] Preferably, in step (4), the ethanol is added at a mass-volume ratio of menthol to ethanol of 3.5-4.0 g: 5 ml.

[0019] Preferably, in step (4), the water dilution is carried out by diluting 100 mL of oil-water mixture to 1000-1100 mL of water.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] (1) The present invention has a high oil yield, while improving the utilization rate of medicinal materials and enhancing the bactericidal and bacteriostatic effects;

[0022] (2) The spray of the present invention can be used directly for nebulization therapy without the need for high-temperature extraction of drug components. It can be used for low-temperature nebulization such as ultrasonic nebulization or compression nebulization, reducing the pain of high-temperature fumigation.

[0023] (3) The spray of the present invention has stable quality and controllable quality, which makes it easier to establish a more specific quality testing method. Attached Figure Description

[0024] Figure 1 The gas chromatography-mass spectrometry chromatogram of the volatile oil in Experiment 1;

[0025] Figure 2 The chromatogram of borneol reference standard in Experiment 3;

[0026] Figure 3 The chromatogram of the menthol reference standard in Experiment 3 is shown below.

[0027] Figure 4 The chromatogram of the test solution in Experiment 3;

[0028] Figure 5 The inclusion curve of sodium sulfonyl ether-β-cyclodextrin on borneol in Experiment 3;

[0029] Figure 6 The inclusion curve of sodium sulfobutyl ether-β-cyclodextrin to menthol in Experiment 3;

[0030] Figure 7 The results of the sterilization experiment in Experiment 4;

[0031] Figure 8 The results are from the antibacterial experiment in Experiment 4. Detailed Implementation

[0032] The present invention will be further described below with reference to the embodiments.

[0033] Example 1

[0034] A method for preparing a nasal spray for treating rhinitis, comprising the following steps:

[0035] (1) Take 60g of Artemisia argyi, 100g of ginseng leaves, 100g of dandelion, 100g of Schizonepeta tenuifolia, 100g of Magnolia biondii, 60g of Saposhnikovia divaricata, and 60g of Scutellaria baicalensis, and pass them through a No. 2 sieve (24 mesh) to make coarse powder of medicinal materials;

[0036] (2) The crude powder of the medicinal material was placed in a volatile oil extraction device, 4000 mL of water was added to cover the medicinal material, and the extraction was carried out at 100°C. 2.4 mL of volatile oil (yield 0.41%) and 97.6 mL of aqueous liquid were collected respectively and mixed to obtain 100 mL of oil-water mixture.

[0037] (3) Add 15g of sodium sulfobutyl-β-cyclodextrin and 30g of polysorbate-80 to the oil-water mixture, shake well until the solution is clear, and obtain the herbal extract;

[0038] (4) Take 4g of menthol and 2g of borneol, dissolve them in 5ml of ethanol, mix them with the herbal extract, dilute with water to 1000ml, and sonicate for 30min to obtain the nasal spray.

[0039] Experiment 1

[0040] Prepare according to the method of Example 1, then take 0.1 ml of the volatile oil described in step (2) and dilute it with ethyl acetate to 100 ml as the test solution.

[0041] Inject the above-mentioned test solution into a gas chromatograph-mass spectrometer and analyze it under the following conditions.

[0042] Analysis conditions:

[0043] Chromatographic column: Agilent-HP-5 column, with 5% phenyl groups and 95% methyl polysiloxane as the stationary phase (30m×320μm×0.25μm).

[0044] Temperature program: Initial temperature 80℃, increase to 100℃ at a rate of 2℃ / min, hold for 5 min, increase to 150℃ at a rate of 3℃ / min, hold for 10 min, increase to 280℃ at a rate of 5℃ / min, hold for 5 min, solvent delay for 5 min.

[0045] Injector temperature: 230℃; Injection volume: 0.2μL; Carrier gas: nitrogen, flow rate: 6mL / min; Split ratio: 20:1; Detector: single quadrupole mass spectrometer detector; Scan range: 50~550Da.

[0046] GC-MS chromatogram of volatile oils as follows Figure 1 .

[0047] The chemical composition analysis results (based on the Agilent-NIST database and our self-built aromatic essential oil database) are shown in Table 1.

[0048] Table 1

[0049]

[0050] Experiment 2

[0051] Investigation of volatile oil extraction methods:

[0052] Weigh the ingredients according to the following ratio: 30g of Artemisia argyi, 50g of ginseng leaves, 50g of dandelion, 50g of Schizonepeta tenuifolia, 30g of Saposhnikovia divaricata, 30g of Scutellaria baicalensis, and 50g of Magnolia biondii.

[0053] (1) Investigation of drug pulverization particle size

[0054] Three sets of experiments were conducted respectively:

[0055] ① Except for Saposhnikovia divaricata and Scutellaria baicalensis, which were cut into slices, the remaining medicinal materials were chopped (1-2 cm long) and placed in a volatile oil extraction device. 1500 mL of water was added to cover the medicinal materials, and extraction was carried out at 100℃. The volatile oil layer was collected. A total of 0.39 ml of volatile oil was obtained.

[0056] ② Take the above-mentioned medicinal materials, crush them, and pass them through a No. 2 sieve (24 mesh). Place the coarse powder of the medicinal materials in a volatile oil extraction device, add 1500mL of water to cover the medicinal materials, and extract at 100℃. Collect the volatile oil layer. A total of 1.05ml of volatile oil was obtained.

[0057] ③ Take the above-mentioned medicinal materials, crush them, and pass them through a No. 5 sieve (80 mesh). Place the fine powder of the medicinal materials in a volatile oil extraction device, add 1500mL of water to cover the medicinal materials, and extract at 100℃. Collect the volatile oil layer. A total of 0.28ml of volatile oil was obtained.

[0058] In summary, pulverizing the medicinal materials into coarse powder through a No. 2 sieve yields the highest amount of volatile oil.

[0059] (2) Investigation of the amount of water added

[0060] Four groups of experiments were conducted respectively:

[0061] ① Take the above-mentioned medicinal materials, crush them, and pass them through a No. 2 sieve (24 mesh). Place the coarse powder of the medicinal materials in a volatile oil extraction device, add 800 mL of water to cover the medicinal materials, and extract at 100℃. Collect the volatile oil layer. A total of 0.75 ml of volatile oil was obtained.

[0062] ② Take the above-mentioned medicinal materials, crush them, and pass them through a No. 2 sieve (24 mesh). Place the coarse powder of the medicinal materials in a volatile oil extraction device, add 1500mL of water to cover the medicinal materials, and extract at 100℃. Collect the volatile oil layer. A total of 1.05ml of volatile oil was obtained.

[0063] ③ Take the above-mentioned medicinal materials, crush them, and pass them through a No. 2 sieve (24 mesh). Place the coarse powder of the medicinal materials in a volatile oil extraction device, add 2900mL of water to cover the medicinal materials, and extract at 100℃. Collect the volatile oil layer. A total of 1.10ml of volatile oil was obtained.

[0064] ④ Take the above-mentioned medicinal materials, crush them, and pass them through a No. 2 sieve (24 mesh). Place the coarse powder of the medicinal materials in a volatile oil extraction device, add 4500mL of water to cover the medicinal materials, and extract at 100℃. Collect the volatile oil layer. A total of 1.07ml of volatile oil was obtained.

[0065] In summary, the extraction efficiency of volatile oils tends to stabilize when the ratio of medicinal material quality to water exceeds 1:5.

[0066] (3) Investigation of extraction temperature

[0067] Three sets of experiments were conducted respectively:

[0068] ① Take the above-mentioned medicinal materials, crush them, and pass them through a No. 2 sieve (24 mesh). Place the coarse powder of the medicinal materials in a volatile oil extraction device, add 1500mL of water to cover the medicinal materials, and extract at 80℃. Collect the volatile oil layer. A total of 0.53ml of volatile oil was obtained.

[0069] ② Take the above-mentioned medicinal materials, crush them, and pass them through a No. 2 sieve (24 mesh). Place the coarse powder of the medicinal materials in a volatile oil extraction device, add 1500mL of water to cover the medicinal materials, and extract at 90℃. Collect the volatile oil layer. A total of 0.98ml of volatile oil was obtained.

[0070] ③ Take the above-mentioned medicinal materials, crush them, and pass them through a No. 2 sieve (24 mesh). Place the coarse powder of the medicinal materials in a volatile oil extraction device, add 1500mL of water to cover the medicinal materials, and extract at 100℃. Collect the volatile oil layer. A total of 1.05ml of volatile oil was obtained.

[0071] In summary, the extraction efficiency of volatile oils tends to stabilize after the extraction temperature reaches 90℃.

[0072] Comparative Example 1

[0073] Weigh the raw materials according to the following ratio: 30g of Artemisia argyi, 50g of ginseng leaves, 50g of dandelion, 50g of Schizonepeta tenuifolia, 30g of Saposhnikovia divaricata, 30g of Scutellaria baicalensis, 50g of Magnolia biondii, 4g of menthol, and 2g of borneol. Take the remaining medicinal materials except for menthol and borneol, pulverize them, and pass them through a No. 5 sieve (80 mesh). Place the fine powder of medicinal materials, menthol, and borneol together in a volatile oil extraction device, add 2000mL of water to cover the medicinal materials, and extract at 100℃. Collect a total of 100ml of volatile oil layer and aqueous layer. A total of 5.8ml of volatile oil and 94.2ml of aqueous solution were obtained, which were diluted with water to 1000ml and used as a control solution for later use.

[0074] Experiment 3

[0075] Explanation of the amount of excipients added:

[0076] Experimental Principle: Inclusion therapy involves the formation of a stable complex by intercalating the drug with the cavity structure of the main molecule, sulfobutyl ether-β-cyclodextrin, thereby improving drug stability, solubility, regulating release rate, and constructing a targeted delivery system. Excess borneol and menthol are added to a certain amount of aqueous solution of sulfobutyl ether-β-cyclodextrin sodium. The content of borneol and menthol dissolved in the aqueous solution is extracted and measured, which represents the inclusion amount of borneol and menthol by sulfobutyl ether-β-cyclodextrin sodium at that mass. A curve is plotted with the mass of sulfobutyl ether-β-cyclodextrin sodium as the x-axis and the inclusion mass of borneol and menthol as the y-axis to analyze the optimal inclusion ratio of borneol and menthol by sulfobutyl ether-β-cyclodextrin sodium.

[0077] Test method:

[0078] Preparation of the test solution: Take 8 test tubes, numbered 1 to 8. Add 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, and 100 mg of sodium sulfobutyl ether-β-cyclodextrin to test tubes 1 to 7 respectively, and dissolve in 10 ml of water. Do not add sodium sulfobutyl ether-β-cyclodextrin to test tube 8, but add 10 ml of water. Then add 0.1 g each of menthol and borneol to each test tube, seal, and sonicate at 60°C for 1 hour. Remove, let stand for 3 hours, accurately pipette 5 ml of the lower layer solution, and extract with 5 ml of ethyl acetate. Use the ethyl acetate solution as the test solution. Separately, take 3 ml of the lower layer solution for sensory testing.

[0079] Preparation of reference solutions: Accurately weigh 25.98 mg of menthol and dissolve it in 25 ml of ethyl acetate to prepare menthol reference solution; accurately weigh 15.20 mg of natural borneol and dissolve it in 10 ml of ethyl acetate to prepare borneol reference solution.

[0080] Instrumentation and Methods:

[0081] Chromatographic column: Agilent-19091N-213 column, polyethylene glycol as stationary phase (30m×320μm×0.25μm).

[0082] Temperature program: Initial temperature 80℃, hold for 3 min, increase to 120℃ at a rate of 10℃ / min, hold for 3 min, increase to 14℃ at a rate of 5℃ / min, hold for 10 min; Injector temperature: 180℃; Injection volume: 1 μL; Carrier gas: Nitrogen, flow rate 6 mL / min; Split ratio 20:1; Detector: Flame ionization detector.

[0083] Results: The chromatogram of borneol reference standard is shown in [the figure]. Figure 2 The chromatogram of menthol reference standard is shown below. Figure 3 The chromatogram of the test solution is shown in [reference needed]. Figure 4 The inclusion complexation curve of sodium sulfonyl ether-β-cyclodextrin for borneol is shown in the figure. Figure 5 The inclusion curve of sodium sulfobutyl ether-β-cyclodextrin for menthol is shown in the figure. Figure 6 .

[0084] The results of the encapsulation experiment of sodium sulfobutyl ether-β-cyclodextrin with borneol and menthol, as well as the drug irritation, are shown in Table 2.

[0085] Table 2

[0086]

[0087] Depend on Figure 6The inclusion effect curves show that the aqueous solution of sodium sulfobutyl ether-β-cyclodextrin has a positive correlation with the inclusion effect of borneol and also with the inclusion effect of menthol, but the optimal ratio is 30:9.26. Therefore, the recommended addition amount of sodium sulfobutyl ether-β-cyclodextrin is 10-15g when the menthol sample amount is 4g.

[0088] Based on patient usage habits and treatment effects, the optimal dosage per person per dose is 10ml. The main components of the prescription are volatile oils, almost insoluble in water; therefore, solubilizers and stabilizers need to be added to prepare an aqueous solution. After screening, sodium sulfonyl ether-β-cyclodextrin and polysorbate-80 were selected as excipients. Both excipients are listed in the pharmacopoeia and are non-toxic and have no side effects. Sodium sulfonyl ether-β-cyclodextrin is a white powder, a sulfonic acid derivative of anionic, highly water-soluble cyclodextrin. It effectively encapsulates lipid-soluble drug molecules to form non-covalent complexes, improving drug stability and water solubility. It is inherently safe, has a wetting effect on the nasal mucosa, and can mitigate drug hemolysis, increasing the adhesion of the formulation to the nasal mucosa and facilitating sustained drug release. Polysorbate-80 is a yellow viscous liquid, a polyol-type nonionic surfactant, and a commonly used excipient in liquid medications, possessing solubilizing, wetting, and stabilizing properties. Experiments have shown that when the polysorbate-80 content is 3%, the volatile oil in the formulation can be completely dissolved, and the solution becomes clear.

[0089] Experiment 4

[0090] Antibacterial and bacteriostatic experiments of the formulation

[0091] The spray prepared in this invention possesses natural antibacterial properties. To verify its antibacterial effect, in vitro antibacterial activity studies were recently conducted. Three bacteria were selected: Gram-negative Escherichia coli (EC), Pseudomonas aeruginosa (PA), and Gram-positive Staphylococcus aureus (SA). All three are pathogenic bacteria that are easily encountered in human activities. In addition to gastrointestinal infections, EC can cause urinary tract infections, arthritis, meningitis, and septicemia. PA can cause skin and subcutaneous tissue infections, otitis media, meningitis, respiratory infections, urinary tract infections, and septicemia. SA is prone to causing purulent infections, such as folliculitis and wound suppuration.

[0092] The antibacterial effect of the nebulized formulation was studied by measuring the minimum sterilization concentration (MIB) and minimum inhibitory concentration (MIC) against three bacteria.

[0093] Materials: Spray prepared according to the method of Example 1 (sample); spray prepared according to the method of Comparative Example 1 (control); Escherichia coli (CMCC(B)44102), Pseudomonas aeruginosa (CMCC(B)10104), and Staphylococcus aureus (CMCC(B)26003) were all purchased from Shanghai Baolu Biotechnology Co., Ltd.; Tryptic soy agar (TSA) and tryptic soy liquid agar (TSB) were both purchased from Beijing Luqiao Technology Co., Ltd.

[0094] Bacterial culture medium

[0095] Tryptic soybean agar solid medium (TSA): Weigh 40g TSA into a reagent bottle, add 1000ml water, mix well, sterilize in a vertical steam oven, and cool for later use.

[0096] Tryptic Soybean Liquid Culture Medium (TSB): Weigh 40g TSB into a reagent bottle, add 1000ml water, mix well, sterilize in a vertical steam oven, and cool for later use.

[0097] Bacterial activation:

[0098] Three types of bacteria were taken from cryopreservation and inoculated onto tryptic soy agar solid medium using the streak plate method. The culture was kept at 37°C until a single colony appeared. Then the culture was transferred to tryptic soy liquid medium and kept at 37°C.

[0099] Drug bacterial contamination assessment:

[0100] Since the main components of the experimental preparation are volatile substances, they cannot be sterilized at high temperatures. The drug solution was inoculated onto TSA medium using an inoculation loop and incubated at 37°C for 18 hours. The results showed no bacterial plaques, proving that the drug solution was sterile.

[0101] Sterilization experiment:

[0102] Take 5 ml, 2.5 ml, and 1.25 ml of the spray and place them in 15 ml test tubes respectively. Dilute with sterilized TSB medium to 10 ml. Use a pipette to add 10 μl each of EC, PA, and SA bacterial suspensions to the test tubes, mix well, and incubate at 37°C for 24 h. Afterward, remove the mixture and observe whether turbidity appears. Take an appropriate amount of the solution from the turbid solution and streak it onto TSA medium. Incubate at 37°C for 24 h and observe whether plaques form on the TSA medium. The lowest concentration of the solution without plaques is the minimum bactericidal concentration (MBC).

[0103] Antibacterial test:

[0104] Take 100ml, 50ml, 25ml, 12.5ml, and 6.25ml of the spray, and mix them with sterilized TSA medium cooled to below 50℃ to a final volume of 200ml, preparing mixed culture media solutions with drug concentrations of 50%, 25%, 12.5%, 6.25%, and 3.125%, respectively. Pour these solutions into bacterial culture dishes and allow them to solidify, serving as the sample group. Using the same method, prepare the control group culture media using the control drug solution from the comparative example. Streak EC, PA, and SA bacterial suspensions into the sample and control group culture media, and incubate at 37℃ for 24 hours. Observe whether plaques appear after incubation. The lowest drug concentration without plaques is the minimum bactericidal concentration (MIC).

[0105] result:

[0106] The MBC and MIC values ​​of the spray against the three bacteria are shown in Table 3. The bactericidal test results are shown in... Figure 7 The results of the antibacterial experiment are shown in [the table]. Figure 8 .

[0107] Figure 7 From left to right, the concentrations of the drug solutions are 50%, 25%, and 12.5%, respectively. Figure 7 In the diagram, A represents Escherichia coli, B represents Staphylococcus aureus, and C represents Pseudomonas aeruginosa. It is evident that a drug concentration exceeding 25% is effective against Escherichia coli, exceeding 50% is effective against Staphylococcus aureus, but has no effect against Pseudomonas aeruginosa.

[0108] Figure 8 The concentrations of the drug solutions from left to right are 50%, 25%, 12.5%, 6.25%, and 3.125%, respectively. Figure 8 In the diagram, A represents Escherichia coli, B represents Staphylococcus aureus, and C represents Pseudomonas aeruginosa. It is evident that drug concentrations exceeding 12.5% ​​inhibit Escherichia coli, exceeding 6.25% inhibit Staphylococcus aureus, and exceeding 50% inhibit Pseudomonas aeruginosa.

[0109] Table 3

[0110]

[0111] Experiment 5

[0112] In vitro anti-inflammatory experiments of the formulation

[0113] The spray prepared in this invention has anti-inflammatory effects. To verify its anti-inflammatory effect, the mouse ear swelling test was used to examine the anti-inflammatory effect of the preparation on acute inflammation, and the cotton ball granulation test was used to examine the anti-inflammatory effect of the preparation on chronic inflammation.

[0114] Materials: The spray prepared according to the method of Example 1 was used as the high-concentration liquid medicine; 100 ml of the high-concentration liquid medicine was diluted with water to 200 ml to obtain the medium-concentration liquid medicine; 50 ml of the high-concentration liquid medicine was diluted with water to 200 ml to obtain the low-concentration liquid medicine; 100 SPF male mice were purchased from Changsha Tianqin Biotechnology Co., Ltd., with the use license number: SYXK Gui 2022-0001; the water was distilled water, and other reagents were all of analytical grade.

[0115] 1. Mouse auricle swelling experiment

[0116] Method: Fifty mice weighing 18 - 22 g were selected and randomly divided into 5 groups, namely the model group, the control group, the high (200%), medium (100%), and low (50%) dose groups of the spray, with 10 mice in each group. A mixed inflammatory agent (volume ratio: 2% croton oil + 20% absolute ethanol +  5% distilled water + 73% ether) was applied to both sides of the right auricle of the mice at a dose of 0.05 ml per mouse. The left ear was used as the model. After 1 hour of inflammation induction, 0.1 ml of the liquid medicine was applied to the inflamed area of the right ear of the mice in the spray group, and an equal amount of the comparative liquid medicine in the comparative example was applied to the control group. After 4 hours, the mice were sacrificed, and both ear shells were cut off. The two ears were overlapped, and ear pieces were punched out with a punch with a diameter of 8 mm and weighed. The swelling degree of each group was calculated as the weight of the right ear piece minus the weight of the left ear piece, and the swelling inhibition rate was calculated according to formula (1):

[0117] (1)

[0118] The results of the mouse auricle swelling model test are shown in Table 4. Compared with the control group in Table 4,

[0119] Table 4

[0120]

[0121] Table 4 shows that the nasal spray has a significant therapeutic effect on the mouse auricle swelling inflammation model. The high-dose group and the medium-dose group have obvious effects (the significance P value is less than 0.05), indicating that the preparation has a therapeutic effect on acute inflammation.

[0122] 2. Mouse cotton ball granulation experiment

[0123] Fifty mice weighing 18–22 g were randomly divided into five groups: a model group, a control group, and high (200%), medium (100%), and low (50%) dose spray groups, with ten mice in each group. An 8% sodium sulfide solution was applied to the mouse abdomen with a cotton ball, and the hair was wiped off with a damp cotton ball after 2 minutes. Twenty-four hours later, the mice were anesthetized with 3% chloral hydrate, and their abdomens were disinfected with povidone-iodine. A small incision was then made, and a sterilized cotton ball (10 ± 0.5 mg) pre-soaked and dried with gentamicin was inserted subcutaneously into the groin area on both sides of the mouse. The wound was then sutured and disinfected again. The high, medium, and low dose spray groups were treated with 0.2 ml of the solution per mouse, applied evenly to the hairless area of ​​the mouse abdomen. The control group received the same volume of the control solution as the control group. After treatment, the hairless area of ​​the mouse abdomen was fixed with gauze. After 4 hours, the drug was removed and the drug was used continuously for 7 days (once a day). 24 hours after the last administration, the mouse was euthanized by cervical dislocation. The cotton balls that had been implanted in the groins of the mouse were removed, and the surrounding connective tissue was also removed. The fat was removed and the mouse was dried in a 60°C oven for 4 hours and weighed. The weight of the granuloma was then calculated using formula (2).

[0124] Granuloma weight = measured weight - original cotton ball weight (2)

[0125] The results of the mouse cotton ball granulation model experiment are shown in Table 5. Table 5 compares the results with the control group. .

[0126] Table 5

[0127]

[0128] Table 5 shows that this nasal spray has a significant therapeutic effect on a mouse model of granulation tissue swelling and inflammation. The high-dose and medium-dose groups showed more significant effects, indicating that this preparation has a therapeutic effect on chronic inflammation.

[0129] Experiment 6 Clinical Trial

[0130] To further illustrate the therapeutic effect of the nasal spray of Embodiment 1 of the present invention, the following experiments are provided for explanation and illustration.

[0131] Experimental Example 1

[0132] One hundred patients with allergic rhinitis, aged 18-60 years (mean 32.1 years) and with a disease duration of 3 months-3 years (mean 14 months), were selected from June 2024 to June 2025. There were no significant differences among patients in terms of age, disease duration, and severity (P>0.05).

[0133] The experimental group used the nasal spray prepared in Example 1, administered once daily for 15 minutes each time, for 7 and 14 consecutive days. Clinical symptoms were observed and recorded in each group. Table 6 shows the comparison of improvement in clinical symptoms and signs after 7 and 14 days of treatment for allergic rhinitis.

[0134] Clinical symptom improvement criteria:

[0135] sneeze

[0136] 1.++++: No attacks observed daily.

[0137] 2. +++: Occasionally occurs every day, sometimes in the morning or at night, or after exposure to allergens.

[0138] 3++: 2 to 3 attacks per day, occurring in the morning or at night or after exposure to allergens.

[0139] 4.+: There are still several paroxysmal attacks every day, more than 3 each time, which occur in the morning or at night or immediately after exposure to allergens.

[0140] 5. -: Sneezing symptoms are the same as before.

[0141] Clear tears

[0142] 1.++++: No clear, watery nasal discharge was observed from the nasal cavity each day.

[0143] 2.++++: Occasionally, clear, watery nasal discharge flows from the nasal cavity every day.

[0144] 3.++: Clear, watery nasal discharge flows from the nasal cavity intermittently every day.

[0145] 4.+: Copious amounts of clear, watery nasal discharge, sometimes dripping involuntarily from the nostrils.

[0146] 5. -: Symptoms of runny nose are the same as before.

[0147] Nasal congestion

[0148] 1.++++: No nasal congestion symptoms were observed daily.

[0149] 2.+++: Occasionally experience nasal congestion every day, on one or both sides, with varying degrees of severity.

[0150] 3.++: Intermittent nasal congestion symptoms every day, on one or both sides, with varying degrees of severity.

[0151] 4.+: Intermittent or persistent nasal congestion, unilateral or bilateral, varying in severity.

[0152] 5. -: Nasal congestion symptoms are the same as before.

[0153] Itchy nose

[0154] 1.++++: No nasal itching symptoms were observed daily.

[0155] 2.+++: Occasionally experience nasal itching every day, on one or both sides, with varying degrees of severity.

[0156] 3.++: Intermittent nasal itching symptoms every day, on one or both sides, with varying degrees of severity.

[0157] 4.+: Intermittent or persistent nasal itching, unilateral or bilateral, varying in severity.

[0158] 5. -: Symptoms of nasal itching are the same as before.

[0159] Standards for improvement of nasal-related signs:

[0160] Inferior turbinate swelling:

[0161] 1.++++: No obvious swelling of the inferior turbinates on both sides.

[0162] 2.+++: Mild swelling of the inferior turbinate on one or both sides (the nasal septum and middle turbinate are still visible).

[0163] 3.++: Moderate swelling of the inferior turbinate on one or both sides (the inferior turbinate is close to the nasal floor and nasal septum, but there is still a small gap).

[0164] 4.+: Severe swelling of the inferior turbinate on one or both sides (the inferior turbinate is close to the nasal floor and nasal septum, and the middle turbinate is not visible), or there are mucosal polypoid changes or polyps.

[0165] 5. -: Inferior turbinate swelling as before.

[0166] Nasal secretions:

[0167] 1.++++: No abnormal secretions were observed in either nasal cavity.

[0168] 2.+++: A small amount of clear / white discharge may be seen in one or both nasal cavities.

[0169] 3++: Moderate amounts of clear / white discharge are visible in one or both nasal cavities.

[0170] 4.+: Excessive clear / white discharge is visible in both or one nasal cavity.

[0171] 5. -: Inferior turbinate swelling as before.

[0172] Table 6

[0173]

[0174] As shown in Table 6, the traditional Chinese medicine formula of the present invention has a significant effect on relieving and improving the symptoms of allergic rhinitis such as sneezing, runny nose, nasal congestion, and nasal itching, and its clinical signs also show significant changes. After treatment, the above-mentioned traditional Chinese medicine nebulization can greatly reduce the clinical symptoms of allergic rhinitis patients.

[0175] Experimental Example 2

[0176] Two hundred patients with allergic rhinitis, aged 18-65 years (mean 35.6 years) and with a disease duration of 6 months-5 years (mean 34 months), were selected from June 2023 to June 2025. The patients were randomly divided into two groups: a treatment group and a control group, with 100 patients in each group. There were no significant differences between the two groups in terms of age, disease duration, and severity (P>0.05).

[0177] The treatment group used the nasal spray prepared in Example 1, administered once daily for 15 minutes each time. The control group used azelastine hydrochloride nasal spray, administered twice daily, with two sprays applied to each nostril. After 14 days of continuous treatment, the clinical symptoms of both groups were observed and statistically analyzed. The comparison of clinical improvement between the treatment and control groups after 14 days of treatment for allergic rhinitis is shown in Table 7.

[0178] Criteria for curing allergic rhinitis:

[0179] Cure: Clinically, there are no symptoms such as nasal itching, nasal congestion, clear nasal discharge, or sneezing, thus achieving clinical cure.

[0180] Improvement: Occasionally, symptoms such as nasal itching, nasal congestion, clear nasal discharge, and sneezing may occur in clinical practice, or the above symptoms may significantly improve.

[0181] Ineffective: Symptoms such as nasal itching, nasal congestion, clear nasal discharge, and sneezing still exist in clinical practice, or the above symptoms do not improve significantly.

[0182] Table 7

[0183]

[0184] Table 7 shows that the total effective rate of the herbal nasal spray of this invention in treating allergic rhinitis patients reached 98%, and the cure rate reached 21%; the total effective rate of azelastine hydrochloride nasal spray was 96%, and the cure rate was 12%. The therapeutic effect of the herbal nasal spray of this invention is significantly better than that of azelastine hydrochloride nasal spray. The herbal nasal spray of this invention is a pure traditional Chinese medicine formula, has no toxic side effects on the human body, is suitable for various patients with allergic rhinitis, has high safety, and excellent therapeutic effect.

[0185] Typical case: (14 days of treatment)

[0186] 1) Lung and Spleen Qi Deficiency Syndrome: Ms. Zhuo, 45 years old. She had experienced recurrent nasal congestion, nasal itching, sneezing, and clear nasal discharge for over two years, accompanied by postnasal drip, fatigue, heaviness in the body, and weakness in the limbs. Her tongue was pale and swollen with teeth marks on the edges, and the coating was thin and white. Her pulse was deep and thready. Nasal endoscopy revealed pale nasal mucosa bilaterally, moderate edema of the inferior turbinates bilaterally, and abundant clear secretions in the inferior nasal meatuses bilaterally. She was prescribed a specially formulated Chinese herbal nasal nebulizer, administered once daily for 15 minutes each time. After 14 days of continuous use, she experienced no further symptoms such as nasal itching, nasal congestion, clear nasal discharge, or sneezing, achieving clinical cure.

[0187] 2) Lung Qi Deficiency and Cold Syndrome: Mr. Wu, male, 18 years old. He had a 3-year history of recurrent nasal congestion, sneezing, and clear nasal discharge, which was most pronounced upon waking and during sleep. He sneezed 5-10 times consecutively upon smelling irritating odors or experiencing temperature changes, followed by a clear nasal discharge. His tongue was pale with a thin white coating, and his pulse was wiry, thready, and slightly deep. Nasal endoscopy revealed mild edema of the inferior turbinates bilaterally, pale nasal mucosa bilaterally, and a moderate amount of clear secretions in both inferior nasal meatuses. He was prescribed a specially formulated Chinese herbal nasal nebulizer, once daily for 15 minutes each time. After 14 days of continuous use, he experienced no further symptoms such as nasal itching, congestion, clear nasal discharge, or sneezing, achieving clinical cure.

[0188] 3) Lung Meridian Latent Heat Syndrome: Ms. Li, 32 years old. She had experienced recurrent nasal congestion and runny nose for over 3 years, with occasional sneezing, coughing, itchy throat, and dry mouth. Her tongue was pale red with a thin, slightly yellow coating, and the tip was slightly red. Her pulse was thready and slightly rapid. Nasal endoscopy revealed pale red nasal mucosa, mild swelling of the bilateral inferior turbinates, and a small amount of whitish secretions in the bilateral inferior nasal meatuses. She was prescribed a specially formulated Chinese herbal nasal nebulizer, administered once daily for 15 minutes each time. After 14 days of continuous use, she experienced no further symptoms such as nasal congestion, runny nose, or sneezing, achieving clinical cure.

[0189] 4) Lung and Kidney Yang Deficiency Syndrome: Mr. Liang, male, 57 years old. For the past 3 years, he had experienced paroxysmal nasal itching, continuous sneezing (more than 3 times each time), clear nasal discharge, and nasal congestion, which was more pronounced in the morning and severe at night. Postnasal drip irritated the pharynx, causing frequent coughing and throat clearing. His tongue was pale with a white, slippery coating, and his pulse was deep, thready, and weak. Nasal endoscopy revealed pale and edematous nasal mucosa bilaterally, with significant swelling of the inferior turbinates bilaterally, and a large amount of clear secretions on the surface. Mild pharyngeal congestion was observed, and both tonsils were grade I enlarged. He was given a specially prepared herbal nasal nebulizer once daily for 15 minutes each time. After 14 days of continuous use, he clinically recovered from nasal congestion, clear nasal discharge, sneezing, and coughing, achieving clinical cure.

[0190] 5) Lung and Spleen Qi Deficiency Syndrome: Mr. Li, male, 34 years old. He had experienced recurrent nasal congestion and clear runny nose for over 7 years, especially at night. He experienced alternating nasal congestion while lying on his side at night, occasionally waking up gasping for air. He felt dizzy upon waking, was generally sensitive to cold, sweated easily, felt fatigued, had a fair appetite, poor sleep, normal urination, and loose stools. His tongue was pale with a thin white coating, and his pulse was thready and weak. Nasal endoscopy revealed pale and edematous nasal mucosa bilaterally, severe swelling of the middle and inferior turbinates bilaterally, and abundant clear secretions in the inferior nasal meatuses bilaterally. He was prescribed a specially formulated Chinese herbal nasal nebulizer, once daily for 15 minutes each time. After 14 days of continuous use, he experienced no further symptoms such as nasal congestion, clear runny nose, or nighttime awakenings, achieving clinical cure.

[0191] 6) Lung and Kidney Yang Deficiency Syndrome: Ms. Qin, 24 years old. She had experienced recurrent nasal congestion for over a year, primarily in the morning and at night. In severe cases, she would breathe through her mouth at night, and wind significantly increased nasal congestion. She also experienced slight runny nose, fatigue, and a history of cold limbs and susceptibility to colds. Her tongue was pale with a thin white coating, and her pulse was deep and thready. Nasal endoscopy revealed pale nasal mucosa bilaterally, severe edema of the inferior turbinates bilaterally, and abundant clear secretions on the surface. She was prescribed a specially formulated Chinese herbal nasal nebulizer, administered once daily for 15 minutes each time. After 14 days of continuous use, she experienced no further symptoms such as nasal congestion, clear runny nose, or mouth breathing at night, achieving clinical cure.

[0192] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A rhinitis spray for treating rhinitis, characterized by, The traditional Chinese medicine raw materials include the following weight parts: Artemisia argyi 50-60 parts, ginseng leaf 90-100 parts, dandelion 90-100 parts, schizonepeta 90-100 parts, siler 50-60 parts, scutellaria 50-60 parts, lily 80-100 parts, menthol 3.5-4 parts, borneol 1.5-2 parts.

2. The nasal spray for treating rhinitis according to claim 1, wherein The rhinitis spray for treating rhinitis further adds sulfobutyl-beta-cyclodextrin sodium 10-30 parts and polysorbate-80 20-60 parts.

3. The method of preparing a nasal spray for rhinitis for treating rhinitis according to claim 1, wherein, The method includes the following steps: (1) Artemisia argyi, ginseng leaf, dandelion, schizonepeta, siler, scutellaria, and lily are sieved to form crude medicinal powder; (2) Water is added to the crude medicinal powder for extraction, and the volatile oil layer and the water layer liquid are collected and mixed to obtain an oil-water mixture; (3) Sulfobutyl-beta-cyclodextrin sodium and polysorbate-80 are added to the oil-water mixture, and the solution is shaken until it is clear to obtain a medicinal extraction liquid; (4) Menthol and borneol are dissolved in ethanol, mixed with the medicinal extraction liquid, and diluted with water to obtain the rhinitis spray for treating rhinitis.

4. The preparation method of the rhinitis spray for treating rhinitis according to claim 3, wherein the sieve mesh of the sieving in step (1) is 20-25 mesh.

5. The preparation method of the rhinitis spray for treating rhinitis according to claim 3, wherein the mass ratio of the crude medicinal powder to water in step (2) is 1:5-10.

6. The preparation method of the rhinitis spray for treating rhinitis according to claim 3, wherein the extraction temperature in step (2) is 90-100°C.

7. The preparation method of the rhinitis spray for treating rhinitis according to claim 3, wherein the volume ratio of the volatile oil layer to the water layer liquid in the oil-water mixture in step (2) is 1-10:90-99.

8. The preparation method of the rhinitis spray for treating rhinitis according to claim 3, wherein the oil-water mixture is collected at 100-110 mL per 550-600 g of crude medicinal powder in step (2).

9. The preparation method of the rhinitis spray for treating rhinitis according to claim 3, wherein the ethanol is added at a mass-volume ratio of 3.5-4 g of menthol to 5 mL of ethanol in step (4).

10. The preparation method of the rhinitis spray for treating rhinitis according to claim 3, wherein the water is added to dilute the oil-water mixture to 1000-1100 mL per 100 mL of oil-water mixture in step (4).

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