Use of recombinant mytilus edulis mucin in the preparation of a nasal physical barrier formulation

Abstract

This invention relates to the fields of preventive medicine and biomedicine, and provides the application of recombinant mussel adhesive protein in the preparation of nasal physical barrier formulations. Utilizing the biological properties of recombinant mussel adhesive protein, a physical barrier is constructed on the nasal mucosa surface. The nasal physical barrier formulation is used to prevent seasonal allergic rhinitis. It is administered intranasally 1-3 times daily, at least 7 days before the start of the allergen exposure season. By pre-constructing a bioadhesive physical barrier on the nasal mucosa surface using recombinant mussel adhesive protein, direct contact between allergens and the nasal mucosa is blocked. This invention achieves a fundamental shift in intervention strategies; overcomes the core technical deficiencies of existing physical barriers; constructs a dual prevention mechanism combining physical and biological methods; and possesses excellent clinical applicability and industrialization value.

Description

Technical Field

[0001] This invention belongs to the fields of preventive medicine and biomedicine, and particularly relates to the application of recombinant mussel adhesive protein in the preparation of nasal physical barrier formulations. Background Technology

[0002] Seasonal allergic rhinitis (SAR), commonly known as hay fever, is a type I hypersensitivity disease triggered by seasonal airborne allergens (mainly pollen, but also including mold spores, dust mites, etc.). It affects approximately 10% to 30% of the global population, and its incidence is increasing annually with air pollution and climate change, making it a significant public health issue. Its core pathological mechanism involves allergens penetrating the nasal mucosal barrier and cross-linking with specific IgE antibodies on the surface of mast cells. This leads to mast cell degranulation and the release of inflammatory mediators such as histamine and leukotrienes, triggering typical symptoms such as paroxysmal sneezing, copious watery nasal discharge, nasal congestion, and nasal itching.

[0003] Current routine management strategies for seasonal allergic rhinitis in clinical practice have many shortcomings, specifically in four aspects:

[0004] Environmental control is not practical: This method requires patients to reduce outdoor activities during peak pollen season, which is difficult to implement effectively due to limitations in work, life and other practical scenarios, and cannot fundamentally avoid contact with allergens;

[0005] Drug treatment is a passive intervention: mainly oral or nasal second-generation antihistamines, nasal corticosteroids, etc., which can only relieve symptoms after they appear. It is a passive treatment, and long-term use is prone to adverse reactions such as drowsiness, nasal dryness, nosebleeds, and even drug dependence.

[0006] Specific immunotherapy has low adoption rate: Although it can fundamentally change the body's immune response, the treatment cycle is as long as 3-5 years, the onset of action is slow, the cost is high, and there is also a potential risk of systemic allergic reactions, which limits its clinical application.

[0007] Existing physical barrier formulations have technical bottlenecks: nasal physical barrier products prepared based on micronized cellulose, bentonite, natural oils, etc., all have insufficient adhesion, weak binding force with the nasal mucosa, and are difficult to resist the continuous action of the nasal mucosa cilia clearance system. The effective residence time of the barrier is only tens of minutes to several hours, requiring frequent re-spraying, and the durability and stability of the preventive effect are extremely poor.

[0008] Mussel adhesive protein (MAP) is a natural biomolecule secreted by the byssal glands of marine mussels. Its molecular structure is rich in 3,4-dihydroxyphenylalanine (DOPA) residues formed through post-translational modification. These residues can form residue pairs with basic amino acid residues, achieving super-strong wet adhesion in aqueous environments through various intermolecular forces. It also possesses excellent biocompatibility, low immunogenicity, and anti-inflammatory, antioxidant, and tissue-repair-promoting biological activities, showing great potential for application in the biomedical field. However, current applications of mussel adhesive protein are all aimed at treating existing pathological conditions; there is no public disclosure regarding its physical adhesion properties for disease prevention, especially for pre-constructing physical barriers to prevent seasonal allergic rhinitis.

[0009] Therefore, the application of recombinant mussel adhesive protein in the preparation of nasal physical barrier formulations is needed to solve the above problems. Summary of the Invention

[0010] The purpose of this invention is to provide the application of recombinant mussel adhesive protein in the preparation of nasal physical barrier formulations to solve the problems mentioned in the background art.

[0011] To achieve the above objectives, the present invention provides the following technical solution:

[0012] The application of recombinant mussel adhesive protein in the preparation of nasal physical barrier formulations utilizes the biological properties of recombinant mussel adhesive protein to construct a physical barrier on the surface of the nasal mucosa. The nasal physical barrier formulation is characterized by being used to prevent seasonal allergic rhinitis. It is administered intranasally 1-3 times daily for at least 7 days before the start of the allergen exposure season. The recombinant mussel adhesive protein pre-constructs a bioadhesive physical barrier on the surface of the nasal mucosa, blocking direct contact between allergens and the nasal mucosa.

[0013] In a further technical solution, the dosage form of the nasal physical barrier preparation is a nasal spray, gel, or nasal drop.

[0014] In a further technical solution, the concentration of recombinant mussel adhesive protein in the nasal cavity physical barrier preparation is 0.05% to 0.5% (weight / volume ratio).

[0015] In a further technical solution, the concentration of recombinant mussel adhesive protein in the nasal cavity physical barrier preparation is 0.1% to 0.3% (weight / volume ratio).

[0016] In a further technical solution, the nasal physical barrier formulation further includes 0.1% to 0.5% (by weight / volume) of a pharmaceutically acceptable moisturizer.

[0017] In a further technical solution, the moisturizer is sodium hyaluronate or trehalose.

[0018] In a further technical solution, the pH value of the nasal physical barrier preparation is 5.5 to 7.0.

[0019] In a further technical solution, the allergen includes one or more of pollen, dust mites, or mold spores.

[0020] A further technical solution is that the recombinant mussel adhesive protein has the biological characteristics of being rich in 3,4-dihydroxyphenylalanine (DOPA) residues, which endow it with super-strong wet adhesion properties, and also has anti-inflammatory and nasal mucosal repair-promoting biological activities.

[0021] A further technical solution is that the nasal physical barrier preparation can resist the action of the nasal mucosal ciliary clearance system and form a strong, stable and long-lasting biophysical barrier on the surface of the nasal mucosa.

[0022] Compared with the prior art, the beneficial effects of the present invention are:

[0023] This invention achieves a fundamental shift in intervention strategies: it reveals for the first time the novel application value of mussel adhesive protein in the prevention of allergic diseases, opens up new indications, and transforms the intervention of seasonal allergic rhinitis from the existing "passive treatment after symptoms appear" to "active prevention before allergen exposure," blocking allergic reactions from the source of the disease, with a preventive effect far superior to existing symptomatic treatment methods.

[0024] This invention addresses the core technical deficiencies of existing physical barriers: by utilizing the natural super-strong wet adhesion properties of recombinant mussel adhesive protein derived from the DOPA structure, the constructed biophysical barrier can form a strong molecular-level bond with the nasal mucosa, effectively resisting the action of the nasal ciliary clearance system, significantly prolonging the effective protection time of the barrier, and completely solving the technical bottlenecks of insufficient adhesion and short protection time of existing physical barrier formulations.

[0025] This invention constructs a dual prevention mechanism combining physical and biological methods: it not only directly blocks allergens through physical barriers, but also utilizes the inherent anti-inflammatory and mucosal repair-promoting biological activities of recombinant mussel adhesive protein to alleviate basic inflammation of the nasal mucosa, repair micro-damage to the mucosa, and enhance the nasal mucosa's own defense capabilities. The synergistic effect of physical and biological protection further enhances the preventive effect.

[0026] This invention possesses excellent clinical applicability and industrialization value: it can be prepared into various dosage forms such as sprays, gels, and nasal drops, suitable for people with different allergy risk levels and different operational abilities (such as children, the elderly, and people with sensitive mucous membranes), and the formulation is mild with a pH value that matches the physiological environment of the nasal mucosa, is non-irritating, and has high safety; at the same time, it establishes a specific time window and dosing regimen of "preventive administration at least 7 days before the allergy season", which is simple to operate and easily accepted by patients.

[0027] To more clearly illustrate the structural features and effects of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the mechanism of action of preventive physical barriers. In the diagram, A represents the model group without barrier protection, where allergens can directly contact the nasal mucosa and trigger allergic reactions; B represents the prevention group with rMAP barrier protection, where recombinant mussel adhesive protein forms a dense biophysical barrier on the surface of the nasal mucosa, effectively blocking direct contact between allergens and the nasal mucosa.

[0029] Figure 2 The bar chart showing the symptom scores of the animal experiment groups in Example 9 visually displays the differences in symptom scores among the blank control group, model group, each preventive dose group, and treatment control group. The scores of each preventive administration group were significantly lower than those of the model group and treatment control group, with the preventive medium dose group having the lowest score.

[0030] Figure 3 The bar chart comparing serum total IgE levels in each group of the animal experiments in Example 9 clearly shows the differences in serum total IgE content among the groups of mice. The serum total IgE level in the prophylactic administration group was much lower than that in the model group and the treatment control group, and the inhibitory effect of the medium-dose prophylactic administration group was the most significant.

[0031] Figure 4 These are representative HE-stained images of the nasal mucosa from each group in the animal experiments of Example 10. A is the blank control group (normal nasal mucosa, no inflammatory infiltration), B is the model group (severe inflammation, with a large number of eosinophils), D is the prevention medium-dose group (mild inflammation, with a small number of inflammatory cells), and F is the treatment control group (moderate inflammation, with a moderate amount of inflammatory cells). It can be visually shown that the degree of nasal mucosal inflammation in the prevention medium-dose group is significantly less than that in the model group and the treatment control group. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0033] The specific implementation of the present invention will be described in detail below with reference to specific embodiments.

[0034] Example 1

[0035] like Figure 1 , Figure 2 and Figure 3As shown, this embodiment of the invention provides a method for preparing a preventive nasal spray, including the formulation of different concentrations and standardized preparation steps. The preparation steps are as follows: recombinant mussel adhesive protein is dissolved in phosphate-buffered saline, sodium hyaluronate is added as a humectant and thickener after complete dissolution and stirred evenly, the pH is adjusted to 6.5 with phosphate buffer, and after filtration through a 0.22 μm filter membrane for sterilization, it is dispensed into nasal spray bottles equipped with metering pumps.

[0036] In this embodiment, each of the low, medium, and high concentration nasal sprays dispenses approximately 100 μL of liquid per puff. All sprays must be stored in a sealed container at 2-8°C. Sodium chloride is added to the formulation to maintain isotonicity, and sodium hyaluronate enhances the moisturizing and adhesive properties. The pH value of 6.5 matches the physiological environment of the nasal mucosa, making it suitable for preventative use by individuals with different allergy risks. The specific components and dosages of each formulation are as follows:

[0037] Table 1 Composition of each formula

[0038] Components Formula I (low concentration) Formula II (Medium Concentration) Formula III (High Concentration) Recombinant mussel adhesive protein 0.05g 0.20g 0.50g Sodium hyaluronate 0.20g 0.20g 0.20g Sodium chloride 0.90g 0.90g 0.90g Phosphate buffer (pH 6.5) Appropriate amount Appropriate amount Appropriate amount Water for Injection Add to 100mL Add to 100mL Add to 100mL

[0039] Example 2

[0040] The difference between this embodiment and Example 1 is that only Formula I from Example 1 is used for the preparation of a low-concentration preventive nasal spray, while the remaining preparation steps, sterilization methods, packaging methods, and storage conditions are the same as in Example 1.

[0041] In this embodiment, the low-concentration formulation contains 0.05% (weight / volume ratio) of recombinant mussel adhesive protein. The formulation is mild and has moderate bioadhesion, making it suitable for people with mild seasonal allergic rhinitis at low allergen exposure levels. It can be administered as a basic preventative treatment before allergy season.

[0042] Example 3

[0043] The difference between this embodiment and Example 2 is that the preparation formula is replaced with Formula II in Example 1 to prepare a medium-concentration preventive nasal spray. The remaining preparation steps, sterilization methods, packaging forms and storage conditions are the same as in Example 2.

[0044] In this embodiment, the recombinant mussel adhesive protein concentration in the prepared medium-concentration formulation is 0.20% (weight / volume ratio), which is within the preferred concentration range of 0.1%-0.3%. Its wet adhesion properties, barrier stability and formulation mildness achieve the optimal balance, making it the core formulation for subsequent animal experiments. It is suitable for people at moderate risk of seasonal allergic rhinitis and is the clinically preferred prophylactic dosage concentration.

[0045] Example 4

[0046] The difference between this embodiment and Example 3 is that the preparation formula is replaced with Formula III in Example 1 to prepare a high-concentration preventive nasal spray. The remaining preparation steps, sterilization methods, packaging forms and storage conditions are the same as in Example 3.

[0047] In this embodiment, the high-concentration formulation contains 0.50% (weight / volume ratio) of recombinant mussel adhesive protein, which is the highest value within the protected concentration range of the invention. It exhibits the strongest bioadhesion, and the constructed physical barrier can more effectively resist the action of the nasal ciliary clearance system, making it suitable for people at high risk of severe seasonal allergic rhinitis due to high exposure to allergens.

[0048] Example 5

[0049] The difference between this embodiment and Example 3 is that the dosage form is changed from nasal spray to nasal gel, and 0.5% carbomer is added as a gel matrix. The remaining formulation, pH adjustment and sterilization steps are the same as in Example 3. After preparation, it is dispensed into nasal gel injectors.

[0050] In this embodiment, the prepared medium-concentration nasal gel has a larger contact area with the nasal mucosa and a longer residence time due to the thickening effect of the gel matrix, which significantly improves the long-lasting protective effect of the physical barrier. Moreover, it is not easily lost after administration, making it suitable for single-dose administration at night to achieve a protective effect on the nasal cavity throughout the night.

[0051] Example 6

[0052] The difference between this embodiment and Example 3 is that the dosage form is changed from nasal spray to nasal drops, the metering pump is removed and replaced with a dropper bottle (approximately 50 μL per drop), while the rest of the formulation, preparation steps and storage conditions are the same as in Example 3.

[0053] In this embodiment, the prepared medium-concentration nasal drops are administered more precisely, allowing direct application to the deep nasal mucosa. The operation is simple, requiring no pressing of the spray bottle, making it suitable for preventative administration to children, the elderly, and other individuals at risk of seasonal allergic rhinitis who have difficulty operating the spray bottle.

[0054] Example 7

[0055] The difference between this embodiment and Example 3 is that the moisturizer is replaced by an equal weight of trehalose instead of sodium hyaluronate. The rest of the formulation, preparation steps and storage conditions are the same as in Example 3.

[0056] In this embodiment, the prepared medium-concentration nasal spray uses trehalose as a natural moisturizer, which has good compatibility with recombinant mussel adhesive protein. It can effectively maintain the moisture of the nasal mucosa and reduce discomfort such as nasal dryness. It is suitable for people at risk of seasonal allergic rhinitis whose nasal mucosa is sensitive and prone to dryness.

[0057] Example 8

[0058] The difference between this embodiment and Example 3 is that the pH value of the preparation is adjusted from 6.5 to 5.5, while the rest of the formulation composition, preparation steps and storage conditions are the same as in Example 3.

[0059] In this embodiment, the prepared medium-concentration nasal spray has a pH value of 5.5, which is within the protective range of 5.5-7.0. The slightly acidic formulation is more compatible with the physiological microenvironment of the nasal mucosa and can minimize the irritation of the formulation to the mucosa. It is suitable for people at risk of seasonal allergic rhinitis with low mucosal tolerance.

[0060] Example 9

[0061] like Figure 1 , Figure 2 and Figure 3 As shown, this invention provides an animal experimental verification method for the prevention of seasonal allergic rhinitis using a recombinant mussel adhesive protein nasal physical barrier preparation. The method includes animal grouping, modeling, drug administration, and setting of detection indicators. The experimental steps are as follows: 60 SPF-grade BALB / c mice are randomly divided into 6 groups (n=10). The BF group is used to establish an allergic rhinitis model induced by ovalbumin (OVA). Each prevention group is given prophylactic drugs according to the predetermined plan, and the treatment control group is given drugs during the stimulation period. After the last stimulation, the relevant indicators are detected.

[0062] In this embodiment, the model was established using the classic method of "intraperitoneal sensitization + nasal provocation". Each prevention group was given low, medium and high concentrations of the spray prepared in Examples 2, 3 and 4, respectively. Through a multi-group control design, the efficacy of prophylactic administration of the recombinant mussel adhesive protein preparation and the differences in the effects of different concentrations and administration frequencies were accurately verified. The specific animal grouping and administration regimen are shown in Table 2 below:

[0063] Table 2 Animal grouping and administration regimen

[0064] Group Dosage time Dosage frequency Dosage concentration Dosage instructions Group A (blank control group) - - - No action taken Group B (Model Group) - - - Sensitization + challenge, PBS administered intranasally Group C (low-dose prevention group) Starting 7 days before sensitization Once a day 0.05% Formula I spray Group D (Prevention Medium-Dose Group) Starting 7 days before sensitization Twice a day 0.20% Formula II spray Group E (High-dose prevention group) Starting 7 days before sensitization 3 times a day 0.50% Formula III spray Group F (treatment control group) Start of the stimulation period Twice a day 0.20% Formula II spray

[0065] Example 10

[0066] The difference between this embodiment and embodiment 9 is that after the experimental index detection is completed, the data is statistically analyzed and the results of the main indexes are sorted out. The remaining experimental grouping, modeling methods, drug administration regimens and detection steps are the same as those in embodiment 9.

[0067] In this embodiment, the detection indicators included symptom scores, serum total IgE levels, and eosinophil counts in the nasal mucosa. Statistical analysis confirmed that the medium-dose group had the best preventive effect, and all indicators showed significant differences compared with the model group and the treatment control group. This fully demonstrates the superiority of the prophylactic administration strategy of recombinant mussel adhesive protein nasal physical barrier preparation, and the 0.20% concentration, twice-daily administration regimen is the optimal preventive regimen. The main experimental results are shown in Table 3 below:

[0068] Table 3. Experimental Results of Main Indicators

[0069] Evaluation indicators Model group (B) Treatment control group (F) Prevention of medium-dose group (D) Statistical significance Symptom score 8.5±1.2 5.2±0.8 2.1±0.5 DvsB,P<0.01;DvsF,P<0.05 Serum total IgE (ng / mL) 450±55 280±40 120±25 DvsB,P<0.01;DvsF,P<0.05 Eosinophil count ( / HPF) 85±11 52±9 18±4 DvsB,P<0.01;DvsF,P<0.05

[0070] Working principle and usage process of this invention:

[0071] Based on the natural molecular structure and biological characteristics of recombinant mussel adhesive protein, and combined with the pathogenesis of seasonal allergic rhinitis, a dual prevention system is constructed with physical barrier as the core and biological assistance as a supplement. This system blocks the occurrence of allergic reactions at the source and addresses the technical shortcomings of existing physical barrier agents. Specifically, this is achieved in detail at three levels:

[0072] I. Precise Construction of Physical Barriers Based on Super-Strong Wet Adhesion of DOPA Residues

[0073] The 3,4-dihydroxyphenylalanine (DOPA) residues abundant in recombinant mussel adhesive protein molecules are the core structural basis for achieving super-strong wet adhesion. DOPA residues can form specific residue pairs with positively charged basic amino acid residues such as lysine. These residue pairs can synergistically displace the hydration layer of the nasal mucosa surface and the protein molecule itself through electrostatic interactions, allowing the recombinant mussel adhesive protein molecules to fully contact the active groups on the surface of nasal mucosal epithelial cells. Subsequently, through various intermolecular forces such as hydrogen bonds, coordination bonds, hydrophobic interactions, and electrostatic interactions, a firm binding to the nasal mucosa is achieved in the aqueous nasal microenvironment. When administered regularly into the nasal cavity for at least 7 days before the start of the allergy season, recombinant mussel adhesive protein can be gradually deposited and formed on the surface of the nasal mucosa, eventually forming a continuous, dense, and crack-free biophysical barrier that completely covers the susceptible areas of the nasal mucosa. This achieves physical blocking of allergens such as pollen, dust mites, and mold spores, preventing direct contact between allergens and nasal mucosal epithelial cells, and completely blocking the progression of the disease from the initiation stage of the allergic reaction.

[0074] II. Strong binding force resists cilia clearance, achieving long-term stability of the physical barrier.

[0075] The nasal mucosal ciliary clearance system is the nasal cavity's natural defense mechanism, continuously clearing foreign objects and substances from the nasal cavity through the regular beating of cilia. This is the core reason why existing physical barrier agents have a short protection time. In this invention, the binding force between recombinant mussel adhesive protein and the nasal mucosa, formed by various intermolecular forces, is far greater than the clearance force of the nasal mucosal cilia. The biophysical barrier it constructs is not a simple surface coating, but rather forms a strong "molecular-level" bond with the mucosal surface, effectively resisting the continuous action of the ciliary clearance system and significantly prolonging the effective residence time of the barrier in the nasal cavity. This solves the technical bottleneck of insufficient adhesion and the need for frequent re-spraying of existing physical barrier agents, achieving long-term protection of the nasal mucosa.

[0076] III. Synergistic effect of inherent biological activity to achieve protection and repair of nasal mucosa.

[0077] In addition to its strong wet adhesion properties, recombinant mussel adhesive protein also possesses inherent and excellent biological activities that can synergistically preventive effects with physical barriers: First, it has anti-inflammatory activity, inhibiting the release of inflammatory factors in the nasal mucosa, alleviating the basic inflammatory state of the mucosa, and reducing the mucosa's sensitivity to allergens; second, it has mucosal repair activity, promoting the proliferation and migration of nasal mucosal epithelial cells, repairing micro-damage to the mucosal surface caused by dryness, friction, etc., improving the nasal mucosa's natural defense barrier, and enhancing the mucosa's own anti-allergic ability; third, it has low immunogenicity and biocompatibility, with excellent compatibility with human tissues, not triggering an immune rejection reaction in the nasal mucosa, and being non-irritating. Long-term use will not damage the nasal mucosa, ensuring the safety of prophylactic administration.

[0078] In summary, this invention achieves proactive, long-lasting, and safe prevention of seasonal allergic rhinitis through a triple action of physical barrier construction, resistance to ciliary clearance, and bioactive assistance, overcoming the technical limitations of existing intervention methods.

[0079] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Application of recombinant mussel adhesive protein in the preparation of nasal cavity physical barrier formulations, characterized by: utilizing the biological properties of recombinant mussel adhesive protein to construct a physical barrier on the surface of the nasal mucosa. Nasal physical barrier preparations are used to prevent seasonal allergic rhinitis. They are administered intranasally 1-3 times daily for at least 7 days before the start of the allergen exposure season. The preparations utilize recombinant mussel adhesive protein to pre-construct a bioadhesive physical barrier on the nasal mucosa surface, blocking direct contact between allergens and the nasal mucosa.

2. The application of the recombinant mussel adhesive protein according to claim 1 in the preparation of nasal physical barrier formulations, characterized in that: The dosage form of the nasal physical barrier preparation is a nasal spray, gel, or nasal drop.

3. The application of the recombinant mussel adhesive protein according to claim 1 in the preparation of nasal physical barrier formulations, characterized in that: In the nasal cavity physical barrier preparation, the concentration of recombinant mussel adhesive protein is 0.05% to 0.5% (weight / volume ratio).

4. The application of the recombinant mussel adhesive protein according to claim 3 in the preparation of nasal physical barrier formulations, characterized in that: In the nasal cavity physical barrier preparation, the concentration of recombinant mussel adhesive protein is 0.1% to 0.3% (weight / volume ratio).

5. The application of the recombinant mussel adhesive protein according to claim 1 in the preparation of nasal physical barrier formulations, characterized in that: The nasal physical barrier formulation further comprises 0.1% to 0.5% (by weight / volume) of a pharmaceutically acceptable moisturizer.

6. The application of the recombinant mussel adhesive protein according to claim 5 in the preparation of nasal physical barrier formulations, characterized in that: The moisturizer is sodium hyaluronate or trehalose.

7. The application of the recombinant mussel adhesive protein according to claim 1 in the preparation of nasal physical barrier formulations, characterized in that: The pH value of the nasal physical barrier preparation is 5.5 to 7.

0.

8. The application of the recombinant mussel adhesive protein according to claim 1 in the preparation of nasal physical barrier formulations, characterized in that: The allergens include one or more of pollen, dust mites, or mold spores.

9. The application of the recombinant mussel adhesive protein according to claim 1 in the preparation of nasal physical barrier formulations, characterized in that: The recombinant mussel adhesive protein is characterized by its super-strong wet adhesion properties due to its rich content of 3,4-dihydroxyphenylalanine (DOPA) residues, and also possesses anti-inflammatory and nasal mucosal repair-promoting biological activities.

10. The application of the recombinant mussel adhesive protein according to claim 1 in the preparation of nasal physical barrier formulations, characterized in that: The nasal physical barrier formulation can resist the action of the nasal mucociliary clearance system and form a strong, stable and long-lasting biophysical barrier on the surface of the nasal mucosa.

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