A florfenicol and metronidazole ear drop and its preparation method

Abstract

The present application relates to the field of veterinary drug technology, in particular, to a kind of florfenicol metronidazole ear drops and preparation method thereof.Wherein, the florfenicol metronidazole ear drops, in parts by weight, include components: 50 150 parts of florfenicol, 10 50 parts of metronidazole, 5 20 parts of component A, wherein the component A includes benzoyl peroxide. Using the above technical solution, by adding component A containing specific ingredients to the florfenicol metronidazole ear drops, the therapeutic effect of otitis externa or otitis media with a long onset time can be improved, and efficient treatment of otitis externa or otitis media is achieved, with good application prospects.

Description

Technical Field

[0001] The present application relates to the technical field of veterinary drugs, and in particular to a florfenicol metronidazole ear drop solution and a preparation method thereof. Background Art

[0002] Household pets such as dogs and cats have a high incidence of otitis externa and otitis media, ranging from 5-20%. Otitis externa is an acute or chronic inflammation of the epithelium lining the external auditory canal, sometimes accompanied by auricular disease or precipitating otitis media. The main symptoms of otitis externa are itching, erythema of the auricle and ear canal, and excessive ear discharge with an odor. In severe cases, suppuration with a foul odor may occur, and even proliferation may obstruct the ear canal.

[0003] In the prior art, ear drops containing florfenicol and metronidazole are commonly used to treat the aforementioned otitis externa or otitis media. Florfenicol, also known as florfenicol, is a new-generation chloramphenicol-based broad-spectrum antibiotic specifically designed for animals. It boasts a broad antimicrobial spectrum, strong antimicrobial activity, good absorption, and widespread distribution in the body. It has no potential for aplastic anemia and is not teratogenic, carcinogenic, or mutagenic. Metronidazole is an antibiotic and antiprotozoal agent used to treat or prevent systemic or localized infections caused by anaerobic bacteria.

[0004] However, existing ear drops have the problem of slow onset, especially for otitis externa or otitis media with a long onset time.

[0005] Therefore, there is an urgent need in the art for a florfenicol metronidazole ear drop solution and a preparation method thereof, and thus the present application is filed. Summary of the Invention

[0006] The purpose of the present application is to provide a florfenicol metronidazole ear drops and a preparation method thereof to solve at least one technical problem described in the background technology.

[0007] Specifically, the first aspect of the present application provides a florfenicol metronidazole ear drop solution, which comprises the following components in parts by weight:

[0008] Florfenicol 50-150 parts,

[0009] 10-50 parts of metronidazole,

[0010] Component A 5-20 parts,

[0011] Wherein, the component A comprises benzoyl peroxide.

[0012] By adopting the above technical solution, by adding component A containing specific ingredients to the florfenicol metronidazole ear drops, the therapeutic effect of otitis externa or otitis media with a long onset time can be improved, and efficient treatment of otitis externa or otitis media can be achieved, which has good application prospects.

[0013] Preferably, the florfenicol metronidazole ear drops comprise the following components in parts by weight:

[0014] 80-120 parts of Florfenicol,

[0015] 20-40 parts of metronidazole,

[0016] Component A 10-18 parts.

[0017] Preferably, the florfenicol metronidazole ear drops comprise the following components in parts by weight:

[0018] 100 parts of Florfenicol,

[0019] 30 parts of metronidazole,

[0020] Component A 15 parts.

[0021] Preferably, the solvent of the florfenicol metronidazole ear drops is one or a combination of propylene glycol, glycerol, and ethanol.

[0022] Preferably, the florfenicol metronidazole ear drops include 8000-12000 parts of solvent.

[0023] Preferably, the component A further comprises polyethylene glycol, and the polyethylene glycol is preferably polyethylene glycol 4000.

[0024] Preferably, the component A further comprises vitamin E.

[0025] Preferably, the component A comprises 3-15 parts of benzoyl peroxide, 1-6 parts of polyethylene glycol, 1-2 parts of vitamin E, and the rest is solvent ethanol.

[0026] Preferably, in the component A, the weight ratio of benzoyl peroxide to polyethylene glycol is 2:1-3:1.

[0027] By adopting the above technical solution, by adding polyethylene glycol, vitamin E and other components to component A, the onset time of the product can be increased and the treatment efficiency of otitis externa or otitis media can be improved.

[0028] Preferably, the florfenicol metronidazole ear drops further comprise 1-10 parts of sodium citrate.

[0029] In a second aspect of the present application, a method for preparing florfenicol metronidazole ear drops is provided, comprising the steps of:

[0030] Prepare a florfenicol-metronidazole solution by heating the first part by weight of the solvent to 35-45° C., adding florfenicol and dissolving it in the solvent, and after it is fully dissolved, adding metronidazole and dissolving it in the solvent;

[0031] Add component A and dissolve component A in the florfenicol metronidazole solution. After it is fully dissolved, adjust the pH to 6.0-7.0 and add a second part by weight of solvent;

[0032] Wherein, the first part by weight is not less than 4 times the second part by weight.

[0033] Preferably, the method for preparing the florfenicol metronidazole ear drops further comprises the following steps after the step of adding component A:

[0034] The solution is filtered, initially filtered using a titanium rod, then finely filtered using a 0.8 μm microporous filter membrane, and then bottled to obtain the finished product.

[0035] Preferably, the method for preparing the florfenicol metronidazole ear drops further comprises the following steps before adding component A:

[0036] Prepare component A, take an appropriate amount of ethanol solvent, add polyethylene glycol and wait for it to fully dissolve, control the temperature to 50-55°C, adjust the pH to 8.0-9.0, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 25-35°C, and add vitamin E.

[0037] In summary, this application has the following beneficial effects:

[0038] 1. The florfenicol metronidazole ear drops provided in this application can improve the therapeutic effect of otitis externa or otitis media with a long onset time by adding component A containing specific ingredients to the florfenicol metronidazole ear drops, achieve efficient treatment of ear diseases, and have good application prospects.

[0039] 2. The florfenicol metronidazole ear drops provided in this application can increase the onset time of the product and improve the treatment efficiency of otitis externa or otitis media by adding polyethylene glycol, vitamin E and other components to component A.

[0040] 3. The preparation method of florfenicol metronidazole ear drops provided in this application can ensure that the product has good stability, thereby ensuring the therapeutic effect over a long period of time and increasing the application range of the product. DETAILED DESCRIPTION

[0041] The exemplary embodiments are described in detail herein. The embodiments described in the following exemplary embodiments are not intended to represent all embodiments consistent with the present application. Instead, they are merely examples of apparatus and methods consistent with certain aspects of the present application as detailed in the appended claims.

[0042] The terms used in this application are for the purpose of describing specific embodiments only and are not intended to limit this application. As used in this application and the appended claims, the singular forms "a," "an," "the," and "the" are intended to include the plural forms, unless the context clearly indicates otherwise. It should also be understood that the term "and / or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.

[0043] The present application will be described in detail below through examples.

[0044] Existing ear drops for treating pet otitis externa or otitis media have the problem of slow onset, especially poor effect on patients with a long onset time. In view of this, the inventive concept of this application is to provide a florfenicol metronidazole ear drop solution and a preparation method thereof that can solve the above-mentioned technical problems, wherein the florfenicol metronidazole ear drop solution comprises the following components, measured by weight: 50-150 parts of florfenicol, 10-50 parts of metronidazole, and 5-20 parts of component A, wherein the component A includes benzoyl peroxide. According to this inventive concept, by adding component A containing specific ingredients to the florfenicol metronidazole ear drop solution, the therapeutic effect of otitis externa or otitis media with a long onset time can be improved, achieving efficient treatment of ear diseases, and having good application prospects.

[0045] In order to better understand the above technical solution, the above technical solution will be described in detail below in conjunction with specific implementation methods. It should be noted that the components not particularly emphasized in this application can all be purchased from commercial channels.

[0046] Experimental Example 1

[0047] Otitis externa is a common disease in pets, but pet owners often do not pay enough attention to the early symptoms of otitis externa, resulting in many pets not starting treatment until a long time after the onset of otitis externa, at which time otitis externa may have induced otitis media.

[0048] During the study, the applicant found that some pets developed obvious symptoms such as pus discharge after a long period of time due to otitis externa. The acidity of the pus would change the environment in which the ear drops were used, especially the pH value of the environment, which would limit the bactericidal effect of the ear drops and affect the treatment of the infected subjects.

[0049] Based on this, the applicant tested the antibacterial activity of ear drops with different components using the following experimental method in this experimental example:

[0050] The test bacteria were Staphylococcus aureus (No.: ATCC43300) and Pseudomonas aeruginosa (No.: ATCC15442), the main pathogens of otitis externa.

[0051] Taking Staphylococcus aureus as an example, the test strain was inoculated into nutrient broth culture medium and the strain concentration was adjusted to 1×106-1×107 cfu / ml.

[0052] Under sterile conditions, 0.1 ml of the bacterial suspension was added to 20 ml of beef extract peptone medium cooled to 40°C. After mixing evenly, the mixture was added to a sterilized culture dish and allowed to stand until solidified.

[0053] Take a 6 mm diameter filter paper, add ear drops after sterilization, adjust the pH and soak it for 1 hour (the pH of different groups was adjusted to 2, 4, and 6 respectively), stick 3 pieces of the filter paper in each bacterial culture dish, culture at a constant temperature of 37 ° C for 24 hours, and then measure the diameter (mm) of the inhibition zone of each treatment.

[0054] A similar experimental method was used for Pseudomonas aeruginosa, which will not be described here.

[0055] Recipe 1

[0056] Take 100 parts of florfenicol and 30 parts of metronidazole;

[0057] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0058] Recipe 2

[0059] Take 100 parts of florfenicol, 30 parts of metronidazole, and 10 parts of amoxicillin;

[0060] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0061] Dissolve amoxicillin in the florfenicol-metronidazole solution and adjust the pH to 7.0 after it is fully dissolved.

[0062] Recipe 3

[0063] Take 100 parts of florfenicol, 30 parts of metronidazole, and 10 parts of ofloxacin;

[0064] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0065] Dissolve ofloxacin in the florfenicol-metronidazole solution and adjust the pH to 7.0 after it is fully dissolved.

[0066] Recipe 4

[0067] Take 100 parts of florfenicol, 30 parts of metronidazole, and 10 parts of vitamin E;

[0068] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0069] Dissolve vitamin E in the florfenicol-metronidazole solution, and after it is fully dissolved, adjust the pH value to 7.0.

[0070] Recipe 5

[0071] Take 100 parts of florfenicol, 30 parts of metronidazole, and 10 parts of polyethylene glycol 4000;

[0072] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0073] Dissolve polyethylene glycol 4000 in the florfenicol-metronidazole solution, and after it is fully dissolved, adjust the pH value to 7.0.

[0074] Recipe 6

[0075] Take 100 parts of florfenicol, 30 parts of metronidazole, and 10 parts of benzoyl peroxide;

[0076] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0077] Dissolve benzoyl peroxide in the florfenicol-metronidazole solution and adjust the pH to 7.0 after it is fully dissolved.

[0078] The components of formulas 1-6 were all from the same batch. The ear drops prepared according to formulas 1-6 were tested for the diameter of the inhibition zone against Staphylococcus aureus and Pseudomonas aeruginosa according to the method in this experimental example.

[0079] Table 1 Inhibition zone diameter (mm) of formula 1-6

[0080]

[0081] According to the results in Table 1, there is no significant difference in the diameter of the inhibition zone of Formulations 1 to 6 at a pH of 6, indicating that the above formulations have good antibacterial ability in a neutral environment.

[0082] When the acidity of the environment increases, at a pH of 2 or 4, the diameters of the inhibition zones of Formulas 1-5 and 6 differ significantly. It is clear that Formula 6 has better antibacterial activity in an acidic environment and is more suitable for subjects with a longer duration of otitis externa.

[0083] Experimental Example 2

[0084] The applicant found in the study that the existing formula takes effect slowly in an acidic environment.

[0085] Based on this, the applicant tested the antibacterial activity of ear drops with different components using the following experimental method in this experimental example:

[0086] The test bacteria were Staphylococcus aureus (No.: ATCC43300) and Pseudomonas aeruginosa (No.: ATCC15442), the main pathogens of otitis externa.

[0087] Taking Staphylococcus aureus as an example, the test strain was inoculated into nutrient broth culture medium and the strain concentration was adjusted to 1×106-1×107 cfu / ml.

[0088] Under sterile conditions, 0.1 ml of the bacterial suspension was added to 20 ml of beef extract peptone medium cooled to 40°C. After mixing evenly, the mixture was added to a sterilized culture dish and allowed to stand until solidified.

[0089] Take a 6mm diameter filter paper, add ear drops after sterilization, adjust the pH to 4 and soak it for 1 hour. Stick 3 pieces of the filter paper in each bacterial culture dish, culture at 37℃ for 24 hours, and measure the diameter (mm) of the inhibition zone at 6 hours, 12 hours, and 24 hours respectively.

[0090] A similar experimental method was used for Pseudomonas aeruginosa, which will not be described here.

[0091] Recipe 7

[0092] Take 100 parts of florfenicol, 30 parts of metronidazole, 10 parts of benzoyl peroxide, and 3 parts of polyethylene glycol 4000;

[0093] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0094] Dissolve benzoyl peroxide and polyethylene glycol 4000 in the florfenicol-metronidazole solution. After they are fully dissolved, adjust the pH to 7.0.

[0095] Recipe 8

[0096] Take 100 parts of florfenicol, 30 parts of metronidazole, 10 parts of benzoyl peroxide, and 2 parts of vitamin E;

[0097] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0098] Dissolve benzoyl peroxide and vitamin E in the florfenicol-metronidazole solution, and after they are fully dissolved, adjust the pH to 7.0.

[0099] Recipe 9

[0100] Take 100 parts of florfenicol, 30 parts of metronidazole, 10 parts of benzoyl peroxide, 3 parts of polyethylene glycol 4000, and 2 parts of vitamin E;

[0101] Take an appropriate amount of propylene glycol solvent and heat it to 40°C, dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole to fully dissolve it.

[0102] Dissolve benzoyl peroxide, polyethylene glycol 4000, and vitamin E in the florfenicol-metronidazole solution. After they are fully dissolved, adjust the pH to 7.0.

[0103] Recipe 10

[0104] Take 100 parts of florfenicol, 30 parts of metronidazole, 10 parts of benzoyl peroxide, 3 parts of polyethylene glycol 4000, and 2 parts of vitamin E;

[0105] Take an appropriate amount of ethanol solvent, add polyethylene glycol 4000 and wait for it to be fully dissolved, control the temperature to 50°C, adjust the pH to 8.0, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 30°C, and add vitamin E to obtain component A.

[0106] Take an appropriate amount of propylene glycol solvent and heat it to 40° C., dissolve florfenicol in the solvent, and after it is fully dissolved, add metronidazole and dissolve it fully to obtain a florfenicol-metronidazole solution.

[0107] Dissolve component A in the florfenicol-metronidazole solution, and after it is fully dissolved, adjust the pH value to 7.0.

[0108] The components of formulas 1-10 were all from the same batch. The ear drops prepared according to formulas 1-10 were tested for the diameter of the inhibition zone against Staphylococcus aureus and Pseudomonas aeruginosa according to the method in this experimental example.

[0109] Table 2 Inhibition zone diameter (mm) of formulations 1-10

[0110]

[0111]

[0112] According to the results in Table 2, comparing Formula 6 to Formula 10, although the difference in the inhibition zone of the above formulas was not obvious after 24 hours of treatment, Formula 6 to Formula 9 were significantly slower than Formula 10 in terms of onset of effect, as reflected in the fact that the diameter of the inhibition zone at 6 hours was significantly smaller than that of Formula 10. This indicates that Formula 10 has a faster onset of effect in an acidic environment (pH = 4) and also has good application prospects.

[0113] The main difference between Formula 9 and Formula 10 lies in the preparation method of the components. Therefore, the preparation method of the ear drops proposed in this application can achieve the technical effect of increasing the speed of the product taking effect in an acidic environment.

[0114] Example 1

[0115] Take 50 parts of florfenicol, 10 parts of metronidazole, and 5 parts of benzoyl peroxide;

[0116] 7000 parts of propylene glycol solvent was heated to 35° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0117] Dissolve benzoyl peroxide in the florfenicol metronidazole solution. After it is fully dissolved, adjust the pH to 6.0 and add 1000 parts of solvent propylene glycol.

[0118] Example 2

[0119] Take 100 parts of florfenicol, 30 parts of metronidazole, and 10 parts of benzoyl peroxide;

[0120] 8000 parts of propylene glycol solvent was heated to 40° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0121] Dissolve benzoyl peroxide in the florfenicol metronidazole solution. After it is fully dissolved, adjust the pH to 6.5 and add 2000 parts of solvent propylene glycol.

[0122] Example 3

[0123] Take 150 parts of florfenicol, 50 parts of metronidazole, and 15 parts of benzoyl peroxide;

[0124] 10,000 parts of propylene glycol solvent was heated to 45° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0125] Dissolve benzoyl peroxide in the florfenicol metronidazole solution. After it is fully dissolved, adjust the pH to 7.0 and add 2000 parts of solvent propylene glycol.

[0126] Example 4

[0127] Take 50 parts of florfenicol, 10 parts of metronidazole, 3 parts of benzoyl peroxide, 1 part of polyethylene glycol 4000, and 1 part of vitamin E;

[0128] 7000 parts of propylene glycol solvent was heated to 35° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0129] Dissolve benzoyl peroxide, polyethylene glycol 4000, and vitamin E in the florfenicol-metronidazole solution. After they are fully dissolved, adjust the pH to 6.0 and add 1000 parts of solvent propylene glycol.

[0130] Example 5

[0131] Take 100 parts of florfenicol, 30 parts of metronidazole, 10 parts of benzoyl peroxide, 6 parts of polyethylene glycol 4000, and 2 parts of vitamin E;

[0132] 8000 parts of propylene glycol solvent was heated to 40° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0133] Dissolve benzoyl peroxide, polyethylene glycol 4000, and vitamin E in the florfenicol metronidazole solution. After they are fully dissolved, adjust the pH to 6.5 and add 2000 parts of solvent propylene glycol.

[0134] Example 6

[0135] Take 150 parts of florfenicol, 50 parts of metronidazole, 15 parts of benzoyl peroxide, 3 parts of polyethylene glycol 4000, and 2 parts of vitamin E;

[0136] 10,000 parts of propylene glycol solvent was heated to 45° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0137] Dissolve benzoyl peroxide, polyethylene glycol 4000, and vitamin E in the florfenicol metronidazole solution. After they are fully dissolved, adjust the pH to 7.0 and add 2000 parts of solvent propylene glycol.

[0138] Example 7

[0139] The scheme of Example 7 is basically the same as that of Example 5, except that the amount of benzoyl peroxide is 6 parts and the amount of polyethylene glycol 4000 is 3 parts.

[0140] Example 8

[0141] The scheme of Example 8 is basically the same as that of Example 5, except that the amount of benzoyl peroxide is 9 parts and the amount of polyethylene glycol 4000 is 3 parts.

[0142] Example 9

[0143] The scheme of Example 9 is basically the same as that of Example 5, except that the amount of benzoyl peroxide is 6 parts and the amount of polyethylene glycol 4000 is 2 parts.

[0144] Example 10

[0145] The scheme of Example 10 is basically the same as that of Example 5, except that the amount of benzoyl peroxide is 3 parts and the amount of polyethylene glycol 4000 is 3 parts.

[0146] Example 11

[0147] The scheme of Example 11 is basically the same as that of Example 5, except that the amount of benzoyl peroxide is 12 parts and the amount of polyethylene glycol 4000 is 3 parts.

[0148] Example 12

[0149] Take 50 parts of florfenicol, 10 parts of metronidazole, 3 parts of benzoyl peroxide, 1 part of polyethylene glycol 4000, and 1 part of vitamin E;

[0150] Take 5 parts of ethanol solvent, add polyethylene glycol 4000 and wait for it to be fully dissolved, control the temperature to 50°C, adjust the pH to 8.0, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 25°C, and add vitamin E to obtain component A.

[0151] 7000 parts of propylene glycol solvent was heated to 35° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0152] Component A was dissolved in the florfenicol metronidazole solution. After it was fully dissolved, the pH value was adjusted to 6.0 and 1000 parts of solvent propylene glycol was added.

[0153] Example 13

[0154] Take 100 parts of florfenicol, 30 parts of metronidazole, 8 parts of benzoyl peroxide, 6 parts of polyethylene glycol 4000, and 2 parts of vitamin E;

[0155] Take 2 parts of ethanol solvent, add polyethylene glycol 4000 and wait for it to be fully dissolved, control the temperature to 52°C, adjust the pH to 8.5, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 30°C, and add vitamin E to obtain component A.

[0156] 8000 parts of propylene glycol solvent was heated to 40° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0157] Component A was dissolved in the florfenicol metronidazole solution. After it was fully dissolved, the pH value was adjusted to 6.5 and 2000 parts of solvent propylene glycol was added.

[0158] Example 14

[0159] Take 150 parts of florfenicol, 50 parts of metronidazole, 15 parts of benzoyl peroxide, 1 part of polyethylene glycol 4000, and 1 part of vitamin E;

[0160] Take 3 parts of ethanol solvent, add polyethylene glycol 4000 and wait for it to be fully dissolved, control the temperature to 55°C, adjust the pH to 9.0, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 35°C, and add vitamin E to obtain component A.

[0161] 10,000 parts of propylene glycol solvent was heated to 45° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0162] Component A was dissolved in the florfenicol metronidazole solution. After it was fully dissolved, the pH value was adjusted to 7.0 and 2000 parts of solvent propylene glycol was added.

[0163] Example 15

[0164] Take 50 parts of florfenicol, 10 parts of metronidazole, 3 parts of benzoyl peroxide, 1 part of polyethylene glycol 4000, 1 part of vitamin E, and 1 part of sodium citrate;

[0165] Take an appropriate amount of ethanol solvent, add polyethylene glycol 4000 and wait for it to be fully dissolved, control the temperature to 50°C, adjust the pH to 8.0, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 25°C, and add vitamin E to obtain component A.

[0166] 7000 parts of propylene glycol solvent was heated to 35° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0167] Component A and sodium citrate were dissolved in the florfenicol-metronidazole solution. After they were fully dissolved, the pH value was adjusted to 6.0, and 1000 parts of solvent propylene glycol was added.

[0168] Example 16

[0169] Take 100 parts of florfenicol, 30 parts of metronidazole, 10 parts of benzoyl peroxide, 6 parts of polyethylene glycol 4000, 2 parts of vitamin E, and 8 parts of sodium citrate;

[0170] Take an appropriate amount of ethanol solvent, add polyethylene glycol 4000 and wait for it to be fully dissolved, control the temperature to 52°C, adjust the pH to 8.5, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 30°C, and add vitamin E to obtain component A.

[0171] 8000 parts of propylene glycol solvent was heated to 40° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0172] Dissolve component A and sodium citrate in the florfenicol-metronidazole solution. After they are fully dissolved, adjust the pH to 6.5 and add 2000 parts of solvent propylene glycol.

[0173] Example 17

[0174] Take 150 parts of florfenicol, 50 parts of metronidazole, 15 parts of benzoyl peroxide, 3 parts of polyethylene glycol 4000, 2 parts of vitamin E, and 10 parts of sodium citrate;

[0175] Take an appropriate amount of ethanol solvent, add polyethylene glycol 4000 and wait for it to be fully dissolved, control the temperature to 55°C, adjust the pH to 9.0, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 35°C, and add vitamin E to obtain component A.

[0176] 10,000 parts of propylene glycol solvent was heated to 45° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0177] Dissolve component A and sodium citrate in the florfenicol-metronidazole solution. After they are fully dissolved, adjust the pH to 7.0 and add 2000 parts of solvent propylene glycol.

[0178] Comparative Example 1

[0179] Take 100 parts of florfenicol and 30 parts of metronidazole;

[0180] 8000 parts of propylene glycol solvent was heated to 40° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole was added and fully dissolved to obtain a florfenicol-metronidazole solution.

[0181] Comparative Example 2

[0182] Take 100 parts of florfenicol, 30 parts of metronidazole, and 8 parts of sodium citrate;

[0183] 8000 parts of propylene glycol solvent was heated to 40° C., and florfenicol was dissolved in the solvent. After the florfenicol was fully dissolved, metronidazole and sodium citrate were added and dissolved fully to obtain a florfenicol-metronidazole solution.

[0184] Test Example 1

[0185] The ear drops prepared according to the methods of Examples 1-17 and Comparative Examples 1-2 were tested for their antibacterial efficacy at pH 4 after 24 hours of treatment according to the method in Experimental Example 2. At the same time, each set of ear drops was applied to pet wounds using conventional methods to observe irritation to the subjects. It is understood that the same batch of products was used for the same set of experiments.

[0186] The experimental results are shown in Table 3.

[0187] Table 3: Efficacy and irritation experiments of Examples 1-17 and Comparative Examples 1-2

[0188]

[0189]

[0190] According to the results in Table 3, we can see that:

[0191] First, the examples provided in this application are safe and have minimal irritation to the subjects;

[0192] Second, compared to existing florfenicol metronidazole ear drops, it has significantly better antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa in acidic environments, making it more suitable for pets or animals with prolonged illness, and has good application prospects.

[0193] Third, comparing Examples 7-9 with Examples 10-11, the difference is that the weight ratio of benzoyl peroxide to polyethylene glycol in Examples 7-9 is within the range of 2:1-3:1, while the weight ratio of benzoyl peroxide to polyethylene glycol in Examples 10-11 is not within the range of 2:1-3:1; and according to the results of Table 3, the antibacterial effect of Example 7-9 is better than that of Example 10-11, which shows that controlling the weight ratio of benzoyl peroxide to polyethylene glycol components has a certain effect on obtaining better drug efficacy;

[0194] Fourth, comparing Examples 15-17 with Examples 12-14, the difference is that a sodium citrate component is added to Examples 15-17; and according to the results in Table 3, Examples 15-17 have better antibacterial effects on Staphylococcus aureus than Examples 12-14, which indicates that the addition of the sodium citrate component has a certain effect on achieving better drug efficacy;

[0195] Fifth, comparing Examples 15-17 with Comparative Example 2, the difference is that Component A is missing in Comparative Example 2. According to the results in Table 3, Comparative Example 2 lacking Component A not only has a worse efficacy than Examples 15-17, but also no longer has a superior antibacterial effect against Staphylococcus aureus. This indicates that the antibacterial effect of sodium citrate against Staphylococcus aureus can only be manifested in combination with other components of the present application.

[0196] For ordinary technicians in this field, the technical features in the above embodiments can be freely combined, and the formed technical solutions also belong to the embodiments disclosed in this application.

[0197] Furthermore, without departing from the principles of the present application, several improvements and modifications may be made to the present application, and these improvements and modifications also fall within the scope of protection of the claims of the present application.

Claims

1. A florfenicol metronidazole ear drop solution, characterized in that: In parts by weight, it includes the following components: Florfenicol 50-150 parts, 10-50 parts of metronidazole, Component A 5-20 parts, Wherein, the component A comprises 3-15 parts of benzoyl peroxide, 1-6 parts of polyethylene glycol, and 1-2 parts of vitamin E.

2. Florfenicol metronidazole ear drops according to claim 1, characterized in that: The florfenicol metronidazole ear drops, in parts by weight, comprise the following components: 80-120 parts of Florfenicol, 20-40 parts of metronidazole, Component A 10-18 parts.

3. Florfenicol metronidazole ear drops according to claim 1 or 2, characterized in that: The solvent of the florfenicol metronidazole ear drops is one or a combination of propylene glycol, glycerol and ethanol.

4. Florfenicol metronidazole ear drops according to claim 1, characterized in that: In the component A, the weight ratio of benzoyl peroxide to polyethylene glycol is 2:1-3:

1.

5. Florfenicol metronidazole ear drops according to claim 4, characterized in that: The florfenicol metronidazole ear drops further comprise 1-10 parts of sodium citrate.

6. A method for preparing the florfenicol metronidazole ear drops according to any one of claims 1 to 5, characterized in that: Including steps: Prepare a florfenicol-metronidazole solution by heating the first part by weight of the solvent to 35-45° C., adding florfenicol and dissolving it in the solvent, and after it is fully dissolved, adding metronidazole and dissolving it in the solvent; Add component A and dissolve component A in the florfenicol metronidazole solution. After it is fully dissolved, adjust the pH to 6.0-7.0 and add a second part by weight of solvent; Wherein, the first part by weight is not less than 4 times the second part by weight.

7. The method for preparing florfenicol metronidazole ear drops according to claim 6, wherein: The preparation method of the florfenicol metronidazole ear drops further comprises the following steps before adding component A: Prepare component A, take an appropriate amount of ethanol solvent, add polyethylene glycol and wait for it to fully dissolve, control the temperature to 50-55°C, adjust the pH to 8.0-9.0, add benzoyl peroxide, stir to fully dissolve it, adjust the temperature to 25-35°C, and add vitamin E.

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