An ear canal cleansing fluid and a method of making the same

Abstract

The application belongs to the technical field of ear canal cleaning preparations, and discloses an ear canal cleaning liquid and a preparation method thereof.The ear canal cleaning liquid comprises carboxymethyl chitosan, hyaluronic acid, glycerol, nanobody bacteriostatic agent 0.20%-0.80%, N, 2, 3-trimethyl-2-isopropylbutyramide, panthenol, sodium bicarbonate and water.Based on the instant cleaning function, the ear canal cleaning liquid provided by the application utilizes the combined action of carboxymethyl chitosan, hyaluronic acid, glycerol and nanobody bacteriostatic agent, so that after the product is flushed, sucked dry or naturally flows out, a very thin and firm adherent film can still be formed on the surface of the ear canal mucosa.The film not only can physically protect the wound, but also can continuously release effective components, improve the residence time of the effective components and achieve long-acting bacteriostasis.The ear canal cleaning liquid is convenient to use, has excellent cleaning effect, small irritation and high drug comfort.

Description

Technical Field

[0001] This invention belongs to the field of ear canal cleaning preparation technology, specifically relating to an ear canal cleaning solution and its preparation method. Background Technology

[0002] For topical treatment of ear canal diseases, ear drops and cleaning solutions have become the most mainstream and fundamental forms of application in clinical practice due to their unique dosage form characteristics. These liquid preparations, with their excellent fluidity, ensure ease of use and even coverage of the affected area. Compared to semi-solid preparations such as ointments and creams, liquids can easily enter the narrow and winding external auditory canal using droppers or spray devices, allowing the medication to reach deeper areas without complicated operations. This solves the technical problems of uneven application and accumulation at the entrance of traditional ointments. Furthermore, as a flushing medium, cleaning solutions soften, suspend, and remove cerumen impaction, purulent secretions, fungal hyphae, and foreign bodies; as a drug carrier, they can directly deliver antibacterial and anti-inflammatory active ingredients to the surface of the infected lesion, achieving high-concentration local drug delivery. In addition, in professional medical procedures, liquid formulations are easily combined with techniques such as negative pressure suction and otoscopy to achieve thorough flushing and drainage of secretions from the ear canal and tympanic membrane, creating a clean environment for subsequent treatment.

[0003] However, commonly used ear cleaning solutions also have their shortcomings, mainly in the short local retention time of the medication. Because the external auditory canal is not a closed cavity, the instilled medication is easily lost due to changes in body position, head movement, or absorption, making it difficult to maintain an effective concentration at the site of action. Multiple daily administrations are often necessary to maintain efficacy, which places high demands on patient compliance. Furthermore, to solubilize certain hydrophobic drug components (such as plant essential oils and some chemical drugs), excipients such as ethanol and surfactants are sometimes introduced into the formulation, which can increase the risk of mucosal irritation.

[0004] Therefore, the development of ear canal cleaning solutions is of great clinical significance and application value. It is important to further improve the retention time of the active ingredients, reduce irritation, and enhance the comfort of use, while taking into account the advantages of convenient use, good coverage, and the combination of cleaning and drug administration. Summary of the Invention

[0005] This invention aims to solve at least one of the technical problems existing in the prior art. To this end, this invention proposes an ear canal cleaning solution and its preparation method. The ear canal cleaning solution provided by this invention, in addition to its immediate cleaning function, utilizes the combined action of carboxymethyl chitosan, hyaluronic acid, glycerin, and nano-sized antibacterial agents to form an extremely thin and firmly adhering film on the ear canal mucosa surface even after rinsing, drying, or natural drainage. This film not only physically protects the wound but also continuously releases effective ingredients, increasing their retention time and achieving long-lasting antibacterial effects.

[0006] This invention provides an ear canal cleaning solution.

[0007] Specifically, an ear canal cleaning solution comprises, by weight percentage: 0.50%-2.00% carboxymethyl chitosan, 0.10%-0.50% hyaluronic acid, 25.00%-40.00% glycerin, 0.20%-0.80% nano-bacterial agent, 0.01%-0.05% N,2,3-trimethyl-2-isopropylbutyramide, 0.50%-1.50% panthenol, 1.20%-2.20% sodium bicarbonate, and 53.00%-70.00% water.

[0008] In some embodiments of the present invention, the ear canal cleaning solution comprises, by weight percentage: 1.00%-1.50% carboxymethyl chitosan, 0.20%-0.50% hyaluronic acid, 28.00%-35.00% glycerin, 0.50%-0.80% nano-bacterial agent, 0.01%-0.03% N,2,3-trimethyl-2-isopropylbutyramide, 0.80%-1.20% panthenol, 1.50%-2.00% sodium bicarbonate, and 60.00%-67.00% water.

[0009] In some embodiments of the present invention, the nanobody antibacterial agent is prepared by cross-linking chitosan, an antibacterial agent, and a cross-linking agent; the antibacterial agent includes drugs that inhibit fungi and / or bacteria.

[0010] In some embodiments of the present invention, the mass ratio of the antibacterial agent to the chitosan is 1:(1-5); preferably, the mass ratio of the antibacterial agent to the chitosan is 1:(2-4).

[0011] In some embodiments of the present invention, the antifungal drugs include triazole antifungal drugs, such as fluconazole; the antibacterial drugs include guanidines and their salt derivatives, such as polyhexamethylene biguanide hydrochloride.

[0012] In some embodiments of the present invention, the preparation method of the nanobody antibacterial agent is as follows: the antibacterial agent is added to the chitosan solution to form a uniform drug-containing dispersion system; a crosslinking agent solution is added dropwise to the drug-containing dispersion system to carry out a crosslinking reaction; after the reaction is completed, the supernatant is removed by centrifugation to obtain a precipitate, which is the nanobody antibacterial agent.

[0013] In some embodiments of the present invention, the mass concentration of the chitosan solution is 0.5-3.0 mg / mL; the mass concentration of the crosslinking agent solution is 1.0-10.0 mg / mL; and the volume ratio of the chitosan solution to the crosslinking agent solution is (3-6):1.

[0014] In some embodiments of the present invention, the crosslinking agent contained in the crosslinking agent solution is sodium tripolyphosphate. The chitosan contained in the chitosan solution has a molecular weight of 50-120 kDa and a degree of deacetylation of 70%-90%, which can balance the particle size and ensure granulation.

[0015] In some embodiments of the present invention, the temperature of the crosslinking reaction is 20-40°C, and the time of the crosslinking reaction is 20-60 min.

[0016] In some embodiments of the present invention, the centrifugation process is to centrifuge at 8000-15000 rpm for 10-30 minutes.

[0017] In some embodiments of the present invention, the ear canal cleaning solution further includes, by weight percentage, 0.10%-0.30% surfactant and / or 0.05%-0.20% preservative. The surfactant may be a nonionic surfactant such as Tween-80 or poloxamer 188, which can reduce the surface tension of the ear canal cleaning solution, enhance its wetting and penetration ability within the ear canal, and make the cleaning solution more easily contact with dirt, cerumen, and other substances in the ear canal to exert its cleaning effect. The preservative may be phenoxyethanol, which can effectively inhibit the growth and reproduction of microorganisms in the ear canal cleaning solution, extend the product's shelf life, and ensure safety during use.

[0018] In some embodiments of the present invention, the ear canal cleaning solution further includes 0.10%-0.40% peppermint flavoring by weight percentage.

[0019] The present invention also provides a method for preparing the above-mentioned ear canal cleaning solution.

[0020] Specifically, the preparation method of the above-mentioned ear canal cleaning solution includes the following steps: Prepare a nanoparticle antibacterial agent; add carboxymethyl chitosan and hyaluronic acid sequentially to a portion of water to obtain a first solution; mix glycerol with the remaining water and add sodium bicarbonate to obtain a second solution; mix the first solution and the second solution, add panthenol, the nanoparticle antibacterial agent and the remaining components, adjust the pH, filter to obtain a filtrate, and prepare an ear canal cleaning solution.

[0021] In some embodiments of the present invention, the portion of water accounts for 60%-80% of the total water consumption.

[0022] In some embodiments of the present invention, the process of preparing the first solution is to heat 60%-80% of water to 65-80°C, slowly add carboxymethyl chitosan while stirring, stir until completely dissolved or uniformly dispersed, cool down to 40-50°C, add hyaluronic acid, and stir until dissolved to obtain the first solution.

[0023] In some embodiments of the present invention, the process of adjusting the pH is to adjust the pH value of the system to 5.5-6.5 using a pH adjuster; the pH adjuster includes, but is not limited to, one or more of citric acid, sodium citrate, hydrochloric acid or sodium hydroxide.

[0024] In some embodiments of the present invention, the filtration process is performed using a microporous membrane with a diameter of 0.22-0.45 μm.

[0025] Compared with the prior art, the beneficial effects of the present invention are as follows: The ear canal cleaning solution provided by this invention comprises sodium bicarbonate, glycerin, carboxymethyl chitosan, 0.10%-0.50% hyaluronic acid, nanoparticle antibacterial agent, N,2,3-trimethyl-2-isopropylbutyramide, and panthenol as its main components. Sodium bicarbonate provides a weakly alkaline environment, softening and expanding earwax within the ear canal, thus altering its physical structure. Glycerin, as a highly moisturizing solvent, promotes hydration, assists in softening earwax, and forms a film-forming system with carboxymethyl chitosan, hyaluronic acid, and the nanoparticle antibacterial agent. This ensures suitable fluidity while improving film-forming properties and drug retention. Carboxymethyl chitosan, as a cationic polymer, combined with hyaluronic acid, the nanoparticle antibacterial agent, and other substances, forms a stable hydrophilic biofilm on the negatively charged ear canal mucosa surface after cleaning through electrostatic interactions. This film anchors other active ingredients to the site of action, significantly prolonging residence time and providing physical isolation from external stimuli. The nanoparticle antibacterial agent utilizes an iontophoresis method, cross-linking chitosan with sodium tripolyphosphate to encapsulate antibacterial drugs such as fluconazole or polyhexamethylene biguanide hydrochloride, forming drug-loaded particles with a nanoscale size. This achieves slow and sustained drug release, overcoming the shortcomings of traditional ear drops, such as short drug residence time and the need for frequent administration. It provides antibacterial protection for several hours or even longer after a single wash. An appropriate amount of N,2,3-trimethyl-2-isopropylbutyramide provides a long-lasting and gentle cooling sensation. When used in combination with panthenol, it not only relieves itching and discomfort, but the addition of panthenol allows it to penetrate the mucous membrane, promoting epithelial cell repair, accelerating the healing of inflammatory wounds, and neutralizing any potential minor irritation. Detailed Implementation

[0026] To enable those skilled in the art to more clearly understand the technical solutions described in this invention, the following embodiments are provided for illustration. It should be noted that the following embodiments do not constitute a limitation on the scope of protection claimed by this invention.

[0027] Unless otherwise specified, the raw materials, reagents or apparatus used in the following examples and comparative examples are available from conventional commercial sources or can be obtained by existing known methods.

[0028] Example 1 An ear canal cleaning solution comprising the following components: Carboxymethyl chitosan 1.20%, hyaluronic acid 0.30%, glycerin 30.00%, nano-bacterial agent 0.60%, N,2,3-trimethyl-2-isopropylbutyramide 0.02%, panthenol 1.00%, sodium bicarbonate 1.80%, surfactant (Tween-80) 0.20%, preservative (phenoxyethanol) 0.10%, peppermint flavor 0.20%, water as balance.

[0029] The method for preparing ear canal cleaning solution is as follows: (1) Chitosan (molecular weight 90 kDa, degree of deacetylation 75%) was dissolved in a 0.5% (v / v) aqueous acetic acid solution and magnetically stirred until completely dissolved. The pH was adjusted to 4.7 to prepare a 1.5 mg / mL chitosan solution. A 0.5% (w / v) TPP aqueous solution was prepared. Fluconazole powder was added to the chitosan solution (the mass ratio of chitosan to fluconazole was 2:1), and Tween 80 (0.025%) was added to assist dispersion to form a uniform drug-containing dispersion system. Under magnetic stirring (150 rpm), the TPP solution was slowly and uniformly added to the above drug-containing dispersion system at a rate of 30 drops / min, with a volume ratio of chitosan solution to the crosslinking agent solution of 5:1. After the addition was complete, the reaction was continued at 35°C for 40 minutes. The reaction suspension was centrifuged at high speed (8000 rpm, 20 minutes), the supernatant was discarded, the precipitate was resuspended with purified water and washed by centrifugation 1-2 times to obtain the nanobody antibacterial agent.

[0030] (2) Heat 70% of the amount of purified water to 70°C, slowly add carboxymethyl chitosan while stirring, stir until evenly dispersed, then cool down to 45°C, add hyaluronic acid, stir until dissolved, and obtain the first solution.

[0031] (3) Mix glycerol with the remaining purified water, add sodium bicarbonate, and stir until completely dissolved to obtain a second solution. Add the second solution to the first solution and stir evenly; then add panthenol and surfactant in sequence, and stir evenly to obtain a mixture. Homogenize the mixture at 3000 rpm for 5 min; then, under stirring conditions, add nano-bacterial agent and N,2,3-trimethyl-2-isopropylbutyramide to the homogenized mixture and stir evenly.

[0032] (4) After adjusting the pH of the system to 6.1, add purified water to the total volume and stir well. Finally, filter and fill the solution to obtain the ear canal cleaning solution.

[0033] Example 2 An ear canal cleaning solution comprising the following components: Carboxymethyl chitosan 1.00%, hyaluronic acid 0.50%, glycerin 32.00%, nano-bacterial agent 0.80%, N,2,3-trimethyl-2-isopropylbutyramide 0.03%, panthenol 1.00%, sodium bicarbonate 1.60%, surfactant (Tween-80) 0.20%, preservative (phenoxyethanol) 0.10%, peppermint flavor 0.20%, water as balance.

[0034] The method for preparing ear canal cleaning solution is as follows: (1) Chitosan (molecular weight 90 kDa, degree of deacetylation 75%) was dissolved in a 0.5% (v / v) aqueous acetic acid solution and magnetically stirred until completely dissolved. The pH was adjusted to 4.7 to prepare a 1.5 mg / mL chitosan solution. A 0.5% (w / v) TPP aqueous solution was prepared. Fluconazole powder was added to the chitosan solution (the mass ratio of chitosan to fluconazole was 2:1), and Tween 80 (0.025%) was added to assist dispersion to form a uniform drug-containing dispersion system. Under magnetic stirring (150 rpm), the TPP solution was slowly and uniformly added to the above drug-containing dispersion system at a rate of 30 drops / min, with a volume ratio of chitosan solution to the crosslinking agent solution of 5:1. After the addition was complete, the reaction was continued at 35°C for 40 minutes. The reaction suspension was centrifuged at high speed (8000 rpm, 20 minutes), the supernatant was discarded, the precipitate was resuspended with purified water and washed by centrifugation 1-2 times to obtain the nanobody antibacterial agent.

[0035] (2) Heat 70% of the amount of purified water to 70°C, slowly add carboxymethyl chitosan while stirring, stir until evenly dispersed, then cool down to 45°C, add hyaluronic acid, stir until dissolved, and obtain the first solution.

[0036] (3) Mix glycerol with the remaining purified water, add sodium bicarbonate, and stir until completely dissolved to obtain a second solution. Add the second solution to the first solution and stir evenly; then add panthenol and surfactant in sequence, and stir evenly to obtain a mixture. Homogenize the mixture at 3000 rpm for 5 min; then, under stirring conditions, add nano-bacterial agent and N,2,3-trimethyl-2-isopropylbutyramide to the homogenized mixture and stir evenly.

[0037] (4) After adjusting the pH of the system to 6.0, add purified water to the total volume and stir well. Finally, filter and fill the solution to obtain the ear canal cleaning solution.

[0038] Example 3 An ear canal cleaning solution comprising the following components: Carboxymethyl chitosan 0.50%, hyaluronic acid 0.30%, glycerin 25.00%, nano-bacterial agent 0.60%, N,2,3-trimethyl-2-isopropylbutyramide 0.05%, panthenol 0.50%, sodium bicarbonate 1.80%, surfactant (Tween-80) 0.20%, preservative (phenoxyethanol) 0.10%, peppermint flavor 0.20%, water as balance.

[0039] The method for preparing ear canal cleaning solution is as follows: (1) Chitosan (molecular weight 90 kDa, degree of deacetylation 75%) was dissolved in a 0.5% (v / v) aqueous acetic acid solution and magnetically stirred until completely dissolved. The pH was adjusted to 4.7 to prepare a 1.5 mg / mL chitosan solution. A 0.5% (w / v) TPP aqueous solution was prepared. Fluconazole powder was added to the chitosan solution (the mass ratio of chitosan to fluconazole was 2:1), and Tween 80 (0.025%) was added to assist dispersion to form a uniform drug-containing dispersion system. Under magnetic stirring (150 rpm), the TPP solution was slowly and uniformly added to the above drug-containing dispersion system at a rate of 30 drops / min, with a volume ratio of chitosan solution to the crosslinking agent solution of 5:1. After the addition was complete, the reaction was continued at 35°C for 40 minutes. The reaction suspension was centrifuged at high speed (8000 rpm, 20 minutes), the supernatant was discarded, the precipitate was resuspended with purified water and washed by centrifugation 1-2 times to obtain the nanobody antibacterial agent.

[0040] (2) Heat 70% of the amount of purified water to 70°C, slowly add carboxymethyl chitosan while stirring, stir until evenly dispersed, then cool down to 45°C, add hyaluronic acid, stir until dissolved, and obtain the first solution.

[0041] (3) Mix glycerol with the remaining purified water, add sodium bicarbonate, and stir until completely dissolved to obtain a second solution. Add the second solution to the first solution and stir evenly; then add panthenol and surfactant in sequence, and stir evenly to obtain a mixture. Homogenize the mixture at 3000 rpm for 5 min; then, under stirring conditions, add nano-bacterial agent and N,2,3-trimethyl-2-isopropylbutyramide to the homogenized mixture and stir evenly.

[0042] (4) After adjusting the pH of the system to 6.1, add purified water to the total volume and stir well. Finally, filter and fill the solution to obtain the ear canal cleaning solution.

[0043] Comparative Example 1 The difference between this comparative example and Example 1 is that carboxymethyl chitosan is not added, hyaluronic acid 0.50%, glycerol 31.00%, and the remaining components and preparation methods are the same as in Example 1.

[0044] Comparative Example 2 The difference between this comparative example and Example 1 is that 0.60% of the nanoparticle antibacterial agent was replaced with 0.40% of chitosan oligosaccharide (molecular weight 90kDa, degree of deacetylation 75%) and 0.20% of fluconazole. The remaining components and preparation methods are the same as in Example 1.

[0045] Comparative Example 3 The difference between this comparative example and Example 1 is that N,2,3-trimethyl-2-isopropylbutyramide is not added, and panthenol is replaced with an equal amount of ethanol. The remaining components and preparation methods are the same as in Example 1.

[0046] Product effectiveness test The ear canal cleaning solutions provided in the embodiments and comparative examples of this invention were tested for effectiveness. The tests included: immediate cleaning effect test, bioadhesive film formation and retention ability test, long-lasting antibacterial effect "after cleaning" test, and skin mildness evaluation. The specific methods are as follows: (1) Instant cleaning effect test Artificial earwax was prepared by mixing beeswax, lanolin, and keratinocyte powder in a mass ratio of 3:1:1 and melted at 50°C. 20 mg of the mixture was evenly applied to the center of the bottom of a 24-well plate, forming a circular spot approximately 5 mm in diameter, and allowed to cool and solidify. 200 μL of the test sample (ear canal cleaning solution provided in the examples and comparative examples) or physiological saline (negative control) was quantitatively added to the earwax spot, and the plate was treated at 37°C for 3 minutes. After treatment, the liquid was immediately and carefully aspirated, and the plate was gently rinsed twice with deionized water. Microscopic observation was used to determine the cleanliness level based on morphological changes (intact / softened edges / partial disintegration / complete disintegration), and the reduction rate of the earwax spot area was calculated using image analysis software. The test results are shown in Table 1.

[0047] Table 1

[0048] Compared to physiological saline, the ear canal cleaning solutions provided in the embodiments and comparative examples of this invention have a stronger ability to dissolve and remove artificial earwax. The cleaning effects of Examples 1 and 2 are superior to Example 3, possibly related to the content of carboxymethyl chitosan and hyaluronic acid. A higher concentration of carboxymethyl chitosan enhances the adhesion and permeability of the solution, more effectively disrupting the earwax structure. Comparative Example 1 achieved complete disintegration even without the addition of carboxymethyl chitosan, suggesting that the synergistic effect of glycerol and sodium bicarbonate may promote its disintegration by altering the physical properties of the earwax.

[0049] (2) Test of biofilm formation and retention capacity An isolated pig ear mucosa (approximately 1 mm thick) was fixed on an inclined plate at a 30° angle to the horizontal. A quantitative drop of 50 μL of the test sample was added to the upper end of the mucosa, allowing it to flow down naturally and cover approximately 1 cm. 2The area was left to stand at room temperature for 2 minutes. Using a microinfusion pump, preheated physiological saline (37°C) and the ear canal cleaning solutions provided in the examples and comparative examples were continuously added from the upper end of the mucosa at a flow rate of 0.5 mL / min for 10 minutes, and all eluent was collected from the lower end. The concentration of fluconazole in the eluent was determined. The drug concentration in the eluent of different treatment groups was compared, and the drug retention rate of different treatment groups was calculated to indirectly evaluate their film-forming and adhesion abilities. The test results are shown in Table 2.

[0050] (3) Test on long-lasting antibacterial effect after cleaning Prepare SDB agar plates. Spread a 0.5% McFarland turbidity standard bacterial suspension (Candida albicans ATCC 10231). Place a sterile Oxford cup (approximately 6 mm in inner diameter) in the center of the plate. Add 100 μL of the test sample (ear canal cleaning solution provided in the examples and comparative examples) to the cup and let it stand at room temperature for 10 minutes to simulate film formation in the ear canal. Carefully aspirate all the liquid from the cup with a pipette and blot dry with sterile filter paper. Pour sterilized and cooled agar to approximately 50°C into the empty Oxford cup until full. Place the plate in a 37°C incubator. Measure and record the diameter of the inhibition zone (including the outer diameter of the Oxford cup) at 24 and 48 hours. The test results are shown in Table 2.

[0051] Table 2

[0052] As shown in Table 2, the ear canal cleaning solution provided in the embodiments of the present invention exhibits good film-forming effect and adhesion ability, retaining more drug and achieving a more lasting antibacterial effect. In Examples 1 and 2, the diameters of the inhibition zones at 24 and 48 hours are larger than those in Example 3, indicating that the content and ratio of carboxymethyl chitosan, hyaluronic acid, and glycerin have a significant impact on the long-lasting antibacterial effect. The preferred formulation content of the present invention further enhances the stability of the bioadhesive film, thereby prolonging the release time of the antibacterial agent. In Comparative Example 1, due to the absence of carboxymethyl chitosan, the drug retention rate was only 18%, and the diameters of the inhibition zones at 24 and 48 hours were 9 mm and 7 mm, respectively, far smaller than those in the Example group, indicating that carboxymethyl chitosan, hyaluronic acid, and glycerin play a crucial role in maintaining the formation and retention of the bioadhesive film in this system. In Comparative Example 2, replacing the nanoparticle antibacterial agent with chitosan oligosaccharide and fluconazole significantly reduced the drug retention rate, failing to achieve a lasting antibacterial effect. Comparative Example 3 shows that N,2,3-trimethyl-2-isopropylbutyramide and panthenol have virtually no effect on the long-lasting antibacterial effect.

[0053] (4) Evaluation of skin mildness Subjects: 48 healthy volunteers (8 in each group).

[0054] Experimental group: ear canal cleaning solution provided in the examples and comparative examples; negative control: 0.9% physiological saline.

[0055] A closed patch test was conducted. 0.1 mL of the experimental group test sample and 0.1 mL of 0.9% saline were respectively placed on filter paper with a diameter of 2.5 cm and applied to the flexor surface of the left and right forearms of the volunteers (integrity skin approximately 5 cm above the crease), and secured with hypoallergenic adhesive tape. The patch was removed after 30 minutes of closed contact. After removal, the test subject rated the comfort level at the application site, recording their sensations during application and whether they experienced burning, stinging, itching, or other symptoms afterward. The test results are shown in Table 3.

[0056] Table 3

[0057] As shown in Table 2, the ear canal cleaning solutions provided in Examples 1-3 and Comparative Examples 1-2 of the present invention have a cooling sensation and high comfort when used; Comparative Example 3 has no cooling sensation because it does not contain N,2,3-trimethyl-2-isopropylbutyramide, and its irritation increases because panthenol is replaced with ethanol.

[0058] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. An ear canal cleaning solution, characterized in that, By weight percentage, it comprises the following components: carboxymethyl chitosan 0.50%-2.00%, hyaluronic acid 0.10%-0.50%, glycerin 25.00%-40.00%, nano-bacterial agent 0.20%-0.80%, N,2,3-trimethyl-2-isopropylbutyramide 0.01%-0.05%, panthenol 0.50%-1.50%, sodium bicarbonate 1.20%-2.20%, and water 53.00%-70.00%.

2. The ear canal cleaning solution according to claim 1, characterized in that, The ear canal cleaning solution comprises, by weight percentage: 1.00%-1.50% carboxymethyl chitosan, 0.20%-0.50% hyaluronic acid, 28.00%-35.00% glycerin, 0.50%-0.80% nano-bacterial agent, 0.01%-0.03% N,2,3-trimethyl-2-isopropylbutyramide, 0.80%-1.20% panthenol, 1.50%-2.00% sodium bicarbonate, and 60.00%-67.00% water.

3. The ear canal cleaning solution according to claim 1 or 2, characterized in that, The nanobody antibacterial agent is prepared by cross-linking chitosan, an antibacterial agent, and a cross-linking agent; the antibacterial agent includes drugs that inhibit fungi and / or bacteria.

4. The ear canal cleaning solution according to claim 3, characterized in that, The preparation method of the nanobody antibacterial agent is as follows: the antibacterial agent is added to the chitosan solution to form a uniform drug-containing dispersion system; the cross-linking agent solution is added dropwise to the drug-containing dispersion system to carry out the cross-linking reaction; after the reaction is completed, the supernatant is removed by centrifugation to obtain the precipitate, which is the nanobody antibacterial agent.

5. The ear canal cleaning solution according to claim 4, characterized in that, The chitosan solution has a mass concentration of 0.5-3.0 mg / mL; the crosslinking agent solution has a mass concentration of 1.0-10.0 mg / mL; and the volume ratio of the chitosan solution to the crosslinking agent solution is (3-6):

1.

6. The ear canal cleaning solution according to claim 5, characterized in that, The cross-linking agent in the cross-linking agent solution is sodium tripolyphosphate; the chitosan in the chitosan solution has a molecular weight of 50-120 kDa and a degree of deacetylation of 70%-90%.

7. The ear canal cleaning solution according to claim 4, characterized in that, The crosslinking reaction is carried out at a temperature of 20-40℃ for 20-60 minutes.

8. The ear canal cleaning solution according to claim 1 or 2, characterized in that, The ear canal cleaning solution also includes 0.10%-0.30% surfactant and / or 0.05%-0.20% preservative.

9. The method for preparing the ear canal cleaning solution according to any one of claims 1-8, characterized in that, Includes the following steps: Prepare a nano-sized antibacterial agent; add carboxymethyl chitosan and hyaluronic acid sequentially to a portion of water to obtain the first solution; Glycerin is mixed with the remaining water, and sodium bicarbonate is added to obtain a second solution. The first and second solutions are then mixed, and panthenol, the nanobody antibacterial agent, and the remaining components are added. The pH is adjusted, and the solution is filtered to obtain a filtrate, thus preparing an ear canal cleaning solution.

10. The preparation method according to claim 9, characterized in that, The process of preparing the first solution is as follows: heating 60%-80% of the formula amount of water to 65-80℃, slowly adding carboxymethyl chitosan while stirring, stirring until completely dissolved or uniformly dispersed, cooling to 40-50℃, adding hyaluronic acid, and stirring until dissolved to obtain the first solution.

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