Compound ear drops for treating otitis media

Abstract

The invention relates to a compound ear drop for treating otitis media, which comprises chloramphenicol, dexamethasone sodium phosphate, a stabilizer, a preservative, a pH regulator, a chelating agent and a solvent, and the weight ratio of chloramphenicol to dexamethasone sodium phosphate is (1-4): 1. The stabilizer is selected from one or more of sodium hyaluronate, polyethylene glycol, povidone, polyvinylpyrrolidone and poloxamer. The ear drops take effect quickly when being used for treating ear diseases, symptoms can be relieved basically after the ear drops are generally used for 3-4 days, after the symptoms are relieved, the ear drops can be re-diagnosed or reduced to be used for one week, and due to the fact that the effect taking time and the treatment course are short, adverse side effects hardly occur.

Description

Technical Field

[0001] The invention relates to the field of medicines, and in particular to a compound ear drop for treating otitis media. Background Art

[0002] Otitis media is an inflammatory disease that affects the middle ear (including the Eustachian tube, tympanic cavity, tympanic sinus and some structures of the mastoid air cells). It is common in children and is a difficult disease to cure. Otitis media can be divided into two categories: non-suppurative and suppurative. Non-suppurative ones include secretory otitis media and barotraumatic otitis media, while suppurative ones can be acute or chronic.

[0003] Chronic otitis media is a common disease in otolaryngology. The most common type is chronic suppurative otitis media, which is often caused by delayed treatment of acute otitis media. Patients experience hearing loss, tympanic membrane perforation, middle ear bone damage, and repeated pus discharge from the ear. If chronic otitis media is not treated correctly, it will further cause internal and external complications of the brain, affecting the patient's quality of life, and in severe cases even threatening life safety.

[0004] Ear drops refer to external liquid preparations that are dripped into the ear canal and have the effects of disinfection, antipruritic, astringent and anti-inflammatory. The dispersion medium of ear drops mainly includes water, ethanol, glycerol, propylene glycol and polyethylene glycol. The commonly used ear drops for treating otitis media are levofloxacin ear drops, which use alcohol as solvent and have the problems of strong local irritation, thereby reducing the patient's compliance.

[0005] Chloramphenicol is a broad-spectrum antibiotic that mainly acts on the 50S subunit of the 70S ribosome of bacteria, preventing the amino acid terminus of aminoacyl tRNA from binding to the receptor on the ribosome to inhibit bacterial protein synthesis, thereby inhibiting bacterial growth. Chloramphenicol has a stronger effect on Gram-negative bacteria than Gram-positive bacteria, and has a stronger effect on Salmonella typhi, Salmonella influenzae and Bordetella pertussis than other antibiotics. It has a good effect on Rickettsial infections (such as typhus) and trachoma virus, and also has a strong antibacterial effect on Brucella, Escherichia coli, Clostridium perfringens, Klebsiella pneumoniae, Shigella dysenteriae, Vibrio cholerae, Neisseria meningitidis, Neisseria gonorrhoeae, etc. Chloramphenicol is mainly used for typhoid, paratyphoid and other Salmonella infections, and is still the first choice for the treatment of these diseases.

[0006] Dexamethasone sodium phosphate mainly has the effect of glucocorticoids and strong anti-inflammatory effect. Its anti-inflammatory mechanism is mainly to reduce and prevent the inflammatory response of tissues, inhibit the accumulation of inflammatory cells, including macrophages and leukocytes at the site of inflammation, and inhibit phagocytosis, the release of lysosomal enzymes, and the synthesis and release of inflammatory mediators. Dexamethasone sodium phosphate is mainly used for the treatment of allergic and autoimmune inflammatory diseases. It is mostly used for the treatment of connective tissue diseases, active rheumatism, rheumatoid arthritis, lupus erythematosus, severe bronchial asthma, severe dermatitis, ulcerative colitis, acute leukemia, etc. It is also used for the comprehensive treatment of certain severe infections and poisonings, and malignant lymphomas.

[0007] So far, there are no reports on the combined use of chloramphenicol and dexamethasone sodium phosphate to treat otitis media with ear drops having good formulation stability. Summary of the invention

[0008] To solve the above technical problems, the present invention includes the following aspects:

[0009] A first aspect of the present invention provides a compound ear drop for treating otitis media, the ear drop comprising chloramphenicol, dexamethasone sodium phosphate, a stabilizer, a preservative, a pH adjuster, a chelating agent and a solvent, the weight ratio of the chloramphenicol to the dexamethasone sodium phosphate being (1-4):1, and the stabilizer being selected from one or more of sodium hyaluronate, polyethylene glycol, povidone, polyvinyl pyrrolidone and poloxamer.

[0010] Preferably, the weight ratio of chloramphenicol to dexamethasone sodium phosphate is (2-3): 1. More preferably, the weight ratio of chloramphenicol to dexamethasone sodium phosphate is (2.2-2.6): 1. Further preferably, the weight ratio of chloramphenicol to dexamethasone sodium phosphate is (2.3-2.5): 1. Most preferably, the weight ratio of chloramphenicol to dexamethasone sodium phosphate is 2.4: 1.

[0011] Preferably, the concentration of chloramphenicol in the ear drops is 0.5-5 mg / mL. More preferably, the concentration of chloramphenicol in the ear drops is 1-3 mg / mL. Further preferably, the concentration of chloramphenicol in the ear drops is 2 mg / mL.

[0012] Preferably, the concentration of dexamethasone sodium phosphate in the ear drops is 0.1-3 mg / mL. More preferably, the concentration of dexamethasone sodium phosphate in the ear drops is 0.5-1 mg / mL. Further preferably, the concentration of dexamethasone sodium phosphate in the ear drops is 0.83 mg / mL.

[0013] Preferably, the stabilizer is selected from one or more of polyethylene glycol and poloxamer. More preferably, the stabilizer is a composition of polyethylene glycol and poloxamer. More preferably, the stabilizer is a composition of polyethylene glycol and poloxamer in a weight ratio of (1:3)-(3:1). Further preferably, the stabilizer is a composition of polyethylene glycol and poloxamer in a weight ratio of (1:2)-(2:1). Further preferably, the stabilizer is a composition of polyethylene glycol and poloxamer in a weight ratio of 1:1. Most preferably, the stabilizer is a composition of polyethylene glycol 400 and poloxamer 188 in a weight ratio of 1:1.

[0014] Preferably, the concentration of the stabilizer in the ear drops is 0.05-0.5 mg / mL. More preferably, the concentration of the stabilizer in the ear drops is 0.05-0.3 mg / mL. Further preferably, the concentration of the stabilizer in the ear drops is 0.1 mg / mL.

[0015] Preferably, the antibacterial agent is selected from one or more of methylparaben, ethylparaben, propylparaben, butylparaben, benzalkonium bromide and benzalkonium chloride. More preferably, the antibacterial agent is benzalkonium bromide.

[0016] Preferably, the concentration of the antibacterial agent in the ear drops is 0.005-0.05 mg / mL. More preferably, the concentration of the antibacterial agent in the ear drops is 0.01-0.03 mg / mL. Further preferably, the concentration of the antibacterial agent in the ear drops is 0.025 mg / mL.

[0017] Preferably, the pH regulator is selected from one or more of hydrochloric acid, boric acid, borax, and citric acid. More preferably, the pH regulator is boric acid.

[0018] Preferably, the concentration of the pH regulator in the ear drops is 0.005-0.05 mg / mL. More preferably, the concentration of the pH regulator in the ear drops is 0.01-0.03 mg / mL. Further preferably, the concentration of the pH regulator in the ear drops is 0.02 mg / mL.

[0019] Preferably, the chelating agent is selected from one or more of disodium edetate, citric acid, metaphosphoric acid, pyrophosphoric acid, and polyphosphoric acid. More preferably, the chelating agent is disodium edetate.

[0020] Preferably, the concentration of the chelating agent in the ear drops is 0.005-0.05 mg / mL. More preferably, the concentration of the chelating agent in the ear drops is 0.01-0.03 mg / mL. Further preferably, the concentration of the chelating agent in the ear drops is 0.02 mg / mL.

[0021] Preferably, the solvent is sterile water.

[0022] Preferably, the contents of the components in the ear drops are as follows: chloramphenicol 0.5-5 mg / mL, dexamethasone sodium phosphate 0.1-3 mg / mL, stabilizer 0.05-0.5 mg / mL, antibacterial agent 0.005-0.05 mg / mL, pH adjuster 0.005-0.05 mg / mL, chelating agent 0.005-0.05 mg / mL, and the balance sterile water.

[0023] Further preferably, the contents of the components in the ear drops are as follows: chloramphenicol 1-3 mg / mL, dexamethasone sodium phosphate 0.5-1 mg / mL, stabilizer 0.02-0.2 mg / mL, antibacterial agent 0.01-0.05 mg / mL, pH adjuster 0.01-0.05 mg / mL, chelating agent 0.01-0.05 mg / mL, and the balance sterile water.

[0024] Further preferably, the contents of the components in the ear drops are as follows: chloramphenicol 1-3 mg / mL, dexamethasone sodium phosphate 0.5-1 mg / mL, polyethylene glycol 4000 0.01-0.1 mg / mL, poloxamer 188 0.01-0.1 mg / mL, benzalkonium bromide 0.01-0.05 mg / mL, boric acid 0.01-0.05 mg / mL, edetate disodium 0.01-0.05 mg / mL, and the balance sterile water.

[0025] Most preferably, the contents of the components in the ear drops are as follows: chloramphenicol 2 mg / mL, dexamethasone sodium phosphate 0.83 mg / mL, polyethylene glycol 4000.05 mg / mL, poloxamer 1880.05 mg / mL, benzalkonium bromide 0.025 mg / mL, boric acid 0.02 mg / mL, edetate disodium 0.02 mg / mL, and the balance sterile water.

[0026] The second aspect of the present invention provides a method for preparing the above-mentioned ear drops, the preparation method comprising the following steps:

[0027] (1) Dissolving the prescribed amount of chloramphenicol and dexamethasone sodium phosphate in an appropriate amount of solvent, mixing the two liquid medicines and stirring them evenly;

[0028] (2) Add the prescribed amount of stabilizer, preservative, pH adjuster and chelating agent to the mixed drug solution in sequence, stir evenly, and add the remaining amount of solvent to the prescribed amount to obtain the drug solution.

[0029] The third aspect of the present invention provides the use of the above ear drops in the preparation of a medicament for treating otitis media.

[0030] Preferably, the otitis media is acute otitis media or chronic otitis media.

[0031] The technical effects produced by the present invention are:

[0032] 1. The present invention optimizes the ratio of chloramphenicol and dexamethasone sodium phosphate in the compound preparation to obtain an ear drop with good effect in treating otitis media. The ear drop of the present invention has a fast onset of action in treating ear diseases, and the symptoms can be basically relieved after 3-4 days of use. After the relief, the patient can generally be re-examined or the dosage can be reduced to one week. Due to the short onset time and treatment course, adverse side effects rarely occur.

[0033] 2. The present invention unexpectedly discovered that adding a stabilizer (e.g., a mixture of polyethylene glycol 400 and poloxamer 188) to a chloramphenicol / dexamethasone sodium phosphate compound preparation can effectively inhibit the chemical degradation of chloramphenicol and dexamethasone sodium phosphate at the same time, thereby solving the stability problem of the active ingredients during storage and transportation of the compound preparation and improving the chemical stability of the drug ingredients in the compound preparation.

[0034] 3. The chloramphenicol / dexamethasone sodium phosphate compound preparation of the present invention uses water as a solvent, which solves the problem of strong local irritation and improves patient compliance compared to conventional therapeutic drugs that use alcohol as a substrate. DETAILED DESCRIPTION

[0035] Example 1: Chloramphenicol / dexamethasone sodium phosphate ear drops D1 of the present invention

[0036] 200 mg of chloramphenicol and 83 mg of dexamethasone sodium phosphate were respectively dissolved in an appropriate amount of sterile water, the two liquid medicines were mixed and stirred evenly, and then 5 mg of polyethylene glycol 400, 5 mg of poloxamer 188, 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium were added in sequence, stirred evenly, and the remaining amount of sterile water was added to 100 mL to obtain the compound ear drops D1 of the present invention.

[0037] Example 2: Chloramphenicol / dexamethasone sodium phosphate ear drops D2 of the present invention

[0038] Dissolve 226 mg of chloramphenicol and 57 mg of dexamethasone sodium phosphate in appropriate amount of sterile water respectively, mix the two liquid medicines and stir evenly, then add 5 mg of polyethylene glycol 400, 5 mg of poloxamer 188, 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium in sequence, stir evenly, add the remaining amount of sterile water to 100 mL, and obtain the compound ear drops D2 of the present invention.

[0039] Example 3: Chloramphenicol / dexamethasone sodium phosphate ear drops D3 of the present invention

[0040] Dissolve 141.5 mg of chloramphenicol and 141.5 mg of dexamethasone sodium phosphate in appropriate amount of sterile water respectively, mix the two liquid medicines and stir evenly, then add 5 mg of polyethylene glycol 400, 5 mg of poloxamer 188, 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium in sequence, stir evenly, add the remaining amount of sterile water to 100 mL, and obtain the compound ear drops D3 of the present invention.

[0041] Example 4: Chloramphenicol / dexamethasone sodium phosphate ear drops D4 of the present invention

[0042] Dissolve 200 mg of chloramphenicol and 83 mg of dexamethasone sodium phosphate in appropriate amount of sterile water respectively, mix the two liquid medicines and stir evenly, then add 10 mg of polyethylene glycol 400, 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium in sequence, stir evenly, add the remaining amount of sterile water to 100 mL, and obtain the compound ear drops D4 of the present invention.

[0043] Example 5: Chloramphenicol / dexamethasone sodium phosphate ear drops D5 of the present invention

[0044] Dissolve 200 mg of chloramphenicol and 83 mg of dexamethasone sodium phosphate in appropriate amount of sterile water respectively, mix the two liquid medicines and stir evenly, then add 10 mg of poloxamer 188, 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium in sequence, stir evenly, add the remaining amount of sterile water to 100 mL, and obtain the compound ear drops D5 of the present invention.

[0045] Example 6: Chloramphenicol / dexamethasone sodium phosphate ear drops D6 of the present invention

[0046] Dissolve 200 mg of chloramphenicol and 83 mg of dexamethasone sodium phosphate in appropriate amount of sterile water respectively, mix the two liquid medicines and stir evenly, then add 10 mg of sodium hyaluronate, 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium in sequence, stir evenly, add the remaining amount of sterile water to 100 mL, and obtain the compound ear drops D6 of the present invention.

[0047] Comparative Example 1, Chloramphenicol / Dexamethasone Sodium Phosphate Ear Drops C1 (compound drug weight ratio is 5:1)

[0048] Dissolve 236 mg of chloramphenicol and 47 mg of dexamethasone sodium phosphate in appropriate amount of sterile water respectively, mix the two liquids and stir evenly, then add 5 mg of polyethylene glycol 400, 5 mg of poloxamer 188, 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium in sequence, stir evenly, add the remaining amount of sterile water to 100 mL, and obtain the compound ear drop comparative example C1.

[0049] Comparative Example 2, Chloramphenicol / Dexamethasone Sodium Phosphate Ear Drops C2 (compound drug weight ratio is 1:2)

[0050] Dissolve 94 mg of chloramphenicol and 189 mg of dexamethasone sodium phosphate in appropriate amount of sterile water respectively, mix the two liquids and stir evenly, then add 5 mg of polyethylene glycol 400, 5 mg of poloxamer 188, 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium in sequence, stir evenly, add the remaining amount of sterile water to 100 mL, and obtain the compound ear drop comparative example C2.

[0051] Comparative Example 3: Chloramphenicol / dexamethasone sodium phosphate ear drops C3 without stabilizer

[0052] Dissolve 200 mg of chloramphenicol and 83 mg of dexamethasone sodium phosphate in appropriate amounts of sterile water, mix the two liquids and stir evenly, then add 2.5 mg of benzalkonium bromide, 2 mg of boric acid and 2 mg of edetate disodium in sequence, stir evenly, add the remaining amount of sterile water to 100 mL, and obtain the compound ear drop comparative example C3.

[0053] Experimental Example 1: Treatment of otitis media model mice with the compound ear drops of the present invention

[0054] 1. Test methods

[0055] 70 Kunming mice were randomly divided into 7 groups, namely, a control group, a model group, an embodiment of the present invention 1-3 group and a comparative example 1-2 group, 10 in each group. Each experimental group of mice was examined by otoscope before modeling to ensure that the tympanic membrane was intact and there was no middle ear effusion. Except for the control group, the external auditory canal of the remaining experimental group mice was disinfected, and 200 μg / mL LPS was slowly injected into the middle ear cavity of one side of the modeling mouse through the front and lower part of the tympanic membrane using a microsyringe, and the control group mice were injected with an equal amount of 0.9% sodium chloride solution in the ipsilateral position. After the modeling was completed, the compound ear drops prepared by the embodiments of the present invention 1-3 and the comparative example 1-2 groups of mice were dripped into the compound ear drops prepared by the embodiments of the present invention 1-3 and the comparative example 1-2 at a dose of 5 mg / kg body weight, and the control group and the model group were dripped into an equal amount of 0.9% sodium chloride solution, twice a day, for 21 consecutive days, and the middle ear lavage fluid was collected 24 hours after the last administration, and the inflammatory factors TNF-α and IL-6 levels in the middle ear lavage fluid of each experimental group of mice were determined according to the ELISA kit instruction manual method.

[0056] 2. Test results

[0057] The effects of the compound ear drops of the present invention on the levels of inflammatory factors in the middle ear lavage fluid of mice with otitis media model are shown in Table 1.

[0058] Table 1 Effect of the compound ear drops of the present invention on the levels of TNF-α and IL-6 in the middle ear lavage fluid of mice

[0059] Experimental Group TNF-α(pg / mL) IL-6 (pg / mL) Control group 12.37±3.65 35.91±4.27 Model Group 84.51±5.14 238.54±29.31 Example 1 Group 32.53±3.89 85.47±6.92 Example 2 Group 53.81±4.06 103.51±7.83 Example 3 Group 57.35±4.73 108.53±7.42 Comparative Example 1 62.93±5.02 147.29±8.05 Comparative Example 2 64.32±4.98 157.34±7.94

[0060] As can be seen from Table 1 above, compared with the control group, the levels of TNF-α and IL-6 in the middle ear lavage fluid of the mice in the model group were significantly increased. Compared with the model group and the comparative example 1-2 group, the levels of TNF-α and IL-6 in the middle ear lavage fluid of the test mice of the ear drops of the embodiment of the present invention 1-3 groups were significantly reduced (with statistical differences), confirming that the compound ear drops of the present invention have produced excellent therapeutic effects on otitis media. Surprisingly, when the total weight of the two active ingredients is the same, compared with other embodiments and comparative examples, the ear drops of the embodiment of the present invention 1 reduce the levels of TNF-α and IL-6 in the middle ear lavage fluid most significantly, confirming that the different ratios of chloramphenicol and dexamethasone sodium phosphate can significantly affect the efficacy of the compound ear drops, and chloramphenicol and dexamethasone sodium phosphate produce a synergistic effect under specific ratios.

[0061] Test Example 2: Study on the chemical stability of the compound ear drops of the present invention

[0062] 1. Test methods

[0063] The chloramphenicol / dexamethasone sodium phosphate ear drops D1, D4-D6 prepared in Examples 1 and 4-6 and the chloramphenicol / dexamethasone sodium phosphate ear drops C3 prepared in Comparative Example 3 were selected, and 5 samples were repeated for each test group. The samples of the above 5 test groups were placed in sealed vials and stored at 60° C. and 75% RH for 10 days. After being taken out, the contents of chloramphenicol and dexamethasone sodium phosphate in each sample were determined, the average values ​​of chloramphenicol and dexamethasone sodium phosphate in each test group were calculated, and the chemical stability of the samples in each test group was evaluated.

[0064] 2. Test results

[0065] Table 2 shows the effects of different types of stabilizers on the chemical stability of the active ingredients chloramphenicol and dexamethasone sodium phosphate in the compound ear drops of the present invention.

[0066] Table 2 Effects of different stabilizers on the chemical stability of active ingredients in compound ear drops

[0067] Experimental Group Chloramphenicol(%) Dexamethasone sodium phosphate (%) Example 1 92.4％ 94.5％ Example 4 85.2％ 87.9％ Example 5 83.8％ 86.3％ Example 6 80.5％ 83.7％ Comparative Example 3 74.5％ 80.2％

[0068] As shown in Table 2 above, compared with Comparative Example 3, the compound ear drops of Examples 1 and 4-6 of the present invention have higher contents of chloramphenicol and dexamethasone sodium phosphate after storage under high temperature and high humidity, indicating that the stabilizer selected in Examples 1 and 4-6 can significantly improve the chemical stability of the two active ingredients in the compound ear drops, effectively inhibit the formation of chloramphenicol and dexamethasone sodium phosphate impurities, and solve the stability problem of the active ingredients during storage and transportation of the compound preparation.

[0069] Test Example 3: Clinical treatment cases of the compound ear drops of the present invention

[0070] Patient 1: Left ear discomfort recurred, and more wet purulent secretions were seen in the left ear canal. The ear canal on the side of the ear was rough. The compound ear drops of Example 1 of the present invention were administered, 3 to 4 drops each time, and the affected ear was kept facing upward for 15 minutes, twice a day. After 3 days, the above symptoms disappeared, the ear was restored to health, and no recurrence has been found in the follow-up so far.

[0071] Patient 2: left ear discomfort recurred, occasional earache; bilateral external auditory canals were unobstructed, rough and congested, with a small amount of cerumen, and the tympanic membrane was intact. The compound ear drops of Example 1 of the present invention were administered, 3 to 4 drops each time, and the affected ear was kept facing upward for 15 minutes, twice a day. After only 2 days, the above symptoms disappeared, the ear was healed, and no recurrence has been observed since follow-up.

[0072] Patient 3: Right earache for 1 day, hearing loss. A large amount of crusts can be seen in both ear canals, and a large amount of fungi grow on the surface. The compound ear drops of Example 1 of the present invention were given, 3 to 4 drops each time, and the affected ear was kept facing upward for 15 minutes, twice a day. After 5 days, the above symptoms disappeared, the ear returned to a healthy state, and no recurrence has been found in the follow-up so far.

[0073] Patient 4: ear discomfort, discharge; right ear canal congestion, more wet secretions can be seen in the deep part of the ear canal. The compound ear drops of Example 1 of the present invention were administered, 3 to 4 drops each time, and the affected ear was kept facing upward for 15 minutes, twice a day. After 3 days, the above symptoms disappeared without recurrence.

[0074] Patient 5: pain in front of right ear for several days, severe when opening mouth and chewing; right ear canal is rough, with a small amount of cerumen. The compound ear drops of Example 1 of the present invention were administered, 3-4 drops each time, and the affected ear was kept facing upward for 15 minutes, twice a day. After 4 days, the above symptoms disappeared, the ear returned to a healthy state, and no recurrence has been found in follow-up so far.

[0075] Patient 6: Ear discomfort, took bath water, bilateral external auditory canals were unobstructed, rough and congested, crusts were visible, a small amount of cerumen, and the tympanic membrane was intact. The compound ear drops of Example 1 of the present invention were administered, 3 to 4 drops each time, and the affected ear was kept facing upward for 15 minutes, twice a day. After 3 days, the above symptoms disappeared, the ear returned to a healthy state, and no recurrence has been observed since follow-up.

[0076] Although specific embodiments of the present invention have been described, it will be appreciated by those skilled in the art that various changes and modifications may be made to the present invention without departing from the scope or spirit of the present invention. Therefore, the present invention is intended to cover all such changes and modifications that fall within the scope of the appended claims and their equivalents.

Claims

1. A compound ear drop for treating otitis media, characterized in that: The ear drops contain chloramphenicol, dexamethasone sodium phosphate, a stabilizer, a preservative, a pH regulator, a chelating agent and a solvent, wherein the weight ratio of the chloramphenicol to the dexamethasone sodium phosphate is (1-4):1, and the stabilizer is selected from one or more of sodium hyaluronate, polyethylene glycol, povidone, polyvinyl pyrrolidone and poloxamer.

2. The compound ear drops according to claim 1, characterized in that The weight ratio of chloramphenicol to dexamethasone sodium phosphate is (2-3):

1.

3. The compound ear drops according to claim 1, characterized in that The stabilizer is a combination of polyethylene glycol and poloxamer.

4. The compound ear drops according to claim 3, characterized in that The stabilizer is a composition of polyethylene glycol and poloxamer in a weight ratio of (1:3)-(3:1).

5. The compound ear drops according to claim 1, characterized in that The antibacterial agent is selected from one or more of methylparaben, ethylparaben, propylparaben, butylparaben, benzalkonium bromide and benzalkonium chloride.

6. The compound ear drops according to claim 1, characterized in that The pH regulator is selected from one or more of hydrochloric acid, boric acid, borax and citric acid.

7. The compound ear drops according to claim 1, characterized in that The chelating agent is selected from one or more of disodium edetate, citric acid, metaphosphoric acid, pyrophosphoric acid and polyphosphoric acid.

8. The compound ear drops according to claim 1, characterized in that The solvent is sterile water.

9. The method for preparing the compound ear drops according to any one of claims 1 to 8, characterized in that: The preparation method comprises the following steps: (1) Dissolving the prescribed amount of chloramphenicol and dexamethasone sodium phosphate in an appropriate amount of solvent, mixing the two liquid medicines and stirring them evenly; (2) Add the prescribed amount of stabilizer, preservative, pH adjuster and chelating agent to the mixed drug solution in sequence, stir evenly, and add the remaining amount of solvent to the prescribed amount to obtain the drug solution.

10. Use of the compound ear drops according to any one of claims 1 to 8 in the preparation of a medicament for treating otitis media.