Nadifloxacin Cream and Its Preparation Method and Application

Abstract

The present invention provides a nadifloxacin cream, its preparation method and application. The active ingredients include the following raw materials in parts by weight: 40 - 60 parts of nadifloxacin raw material medicine, 25 - 43 parts of oily matrix, 15 - 35 parts of emulsifier, 5 - 10 parts of compound penetration enhancer, 5 - 12 parts of humectant, 3 - 6 parts of preservative, and 12 - 25 parts of purified water. The compound penetration enhancer is composed of baicalein, turmeric, enzyme inhibitor peptide, and withaferin A in a specific ratio. During the preparation process, a cream base is formed through steps such as heating, mixing, and emulsifying, then the active ingredients and preservatives are added, and high-voltage pulsed electric field and ozone intermittent treatment are used to improve the penetration performance of the cream. The cream can be used to treat skin infection diseases caused by various bacteria. The present invention provides a new strategy for the development of highly efficient and safe skin medications, is expected to improve the therapeutic effect of nadifloxacin cream, and provides strong support for the clinical treatment of skin infection diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and particularly relates to a nadifloxacin cream, a preparation method thereof and an application thereof. Background Art

[0002] Since the skin covers the surface of the body, it is very easy to come into contact with various pathogens such as dermatophytes and candida on the skin and cause the risk of infection. Moreover, the skin and hair of animals often suffer from skin diseases due to the parasitism of various bacteria, fungi and molds. Skin infection is one of the common clinical diseases, and the infections caused by microorganisms such as Propionibacterium acnes, Staphylococcus epidermidis, Gram-positive bacteria, Gram-negative bacteria and anaerobic bacteria are particularly common. These pathogens multiply on the skin surface or in deep tissues, leading to a series of skin inflammations and injuries, bringing discomfort and pain to patients.

[0003] Fluorquinolone Cream is a kind of topical cream preparation containing fluoroquinolone antibacterial drugs. Fluoroquinolones are synthetic antibacterial drugs that play a broad-spectrum antibacterial role by inhibiting bacterial DNA replication and cell division, and occupy a place in the treatment of skin infections with their broad-spectrum antibacterial activity. However, the existing nadifloxacin cream has some limitations in practical applications. In particular, the transdermal penetration rate of the emulsion is too slow, which limits the rapid arrival of drug components at the infection site and affects the treatment effect. Transdermal absorption is a key step for topical drugs. If the penetration rate is insufficient, the drug may not reach the local concentration required for treatment within the effective time, thereby reducing the efficacy of the drug, prolonging the treatment cycle, increasing the economic burden of patients and the discomfort caused by the disease. In addition, the physical stability of the emulsion is also an important factor affecting the transdermal absorption of drugs. The stability of the emulsion is directly related to the drug release behavior and transdermal absorption efficiency. The creams in the prior art may have problems of insufficient stability, resulting in phenomena such as delamination and precipitation during storage and use, further affecting the uniformity of the drug and the treatment effect. Summary of the Invention

[0004] In view of this, the present invention provides a nadifloxacin cream, a preparation method thereof and an application thereof to solve the above problems.

[0005] The technical solution of the present invention is realized as follows: A nadifloxacin cream: The active ingredients include the following raw materials in parts by weight: 40-60 parts of nadifloxacin raw material medicine, 25-43 parts of oily matrix, 15-35 parts of emulsifier, 5-10 parts of compound penetration enhancer, 5-12 parts of moisturizer, 3-6 parts of preservative, and 12-25 parts of purified water. The compound penetration enhancer is baicalein, turmeric, enzyme inhibitor peptide, and withanolide in a mass ratio of (1.5-3.9):(2.2-5.2):(8.1-10.6):(0.2-0.8).

[0006] Further, the active ingredients include the following raw materials in parts by weight: 50 parts of nadifloxacin raw material medicine, 35 parts of oily matrix, 25 parts of emulsifier, 8 parts of compound penetration enhancer, 9 parts of moisturizer, 5 parts of preservative, and 18 parts of purified water.

[0007] Further, the oily matrix is selected from one or more of lard, lanolin, petroleum ether, white petrolatum, beeswax, and liquid paraffin.

[0008] Further, the emulsifier is selected from any one of astragalus gum, gum arabic, span 80, span 85, polysorbate 80, sodium lauryl sulfate, poloxamer, and PEG-7 olive oil ester.

[0009] Further, the moisturizer is glycerol, methyl cellulose, and oat β-glucan in a mass ratio of (8-15):(2-5):(1-3).

[0010] Further, the preservative is selected from any one of phenylmercuric acetate, benzalkonium chloride, benzalkonium bromide, p-hydroxybenzoate, sodium benzoate, sorbic acid, chlorobutanol, methylparaben, and povidone iodine.

[0011] Further, a preparation method of a nadifloxacin cream includes the following steps:

[0012] i), Heat the oily matrix to a molten state at 60-80 °C;

[0013] ii), Add an emulsifier to the oily matrix and mix evenly at a rate of 400-600 rpm to form an oil-water mixture for standby;

[0014] iii) Mix the purified water and the moisturizer evenly to form a mixed solution for standby;

[0015] iv) Gradually add the above oil-water mixture to the mixed solution at a rate of 1-5 mL / min, and stir with a high-speed shear emulsifier at 2000-3000 rpm while adding until a uniform cream base is formed;

[0016] v) During the cooling process, nadifloxacin raw material, a compound penetration enhancer and a preservative are added, and stirred until completely dissolved, and then intermittently treated with high-voltage pulsed electric field for 2-4 times, 1-5 s each time. During the treatment process, ozone is simultaneously introduced to obtain a uniformly dispersed nadifloxacin cream.

[0017] Furthermore, the electric field strength of the high-voltage pulsed electric field is 20-50 kV / cm, the pulse frequency is 300-500 Hz, the pulse width is 3-8 μs, and the ozone introduction flow rate is 2-5 L / min.

[0018] Furthermore, an application of a nadifloxacin cream in the preparation of a drug for treating skin infectious diseases.

[0019] Furthermore, an application of a nadifloxacin cream in the preparation of a drug for treating skin infections caused by Propionibacterium acnes, Staphylococcus epidermidis, Gram-positive bacteria, Gram-negative bacteria and anaerobic bacteria.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] (1) The nadifloxacin cream described in this scheme adopts an optimized formulation design. By carefully selecting raw materials and controlling their proportions, the cream not only maintains good stability and permeability, but also has high antibacterial activity. Especially the selection of nadifloxacin raw material makes it have strong killing and inhibitory effects on various skin infection pathogens such as Propionibacterium acnes, Staphylococcus epidermidis, Gram-positive bacteria, Gram-negative bacteria and anaerobic bacteria, thus effectively treating skin infectious diseases caused by these microorganisms.

[0022] (2) A specific compound penetration enhancer is adopted. This compound penetration enhancer is composed of baicalein, turmeric, enzyme inhibitor peptide and withanolide, and is formulated strictly according to a certain proportion. This compound penetration enhancer can significantly improve the penetration performance of the cream, enabling drug molecules to penetrate deeper into the skin more quickly, thereby improving the treatment effect. At the same time, the components in the compound penetration enhancer also have certain anti-inflammatory and antioxidant effects, which help to reduce skin inflammatory reactions and promote skin repair and regeneration.

[0023] (3) The preparation method described in the scheme adopts the processes of intermittent treatment with high-voltage pulsed electric field and introduction of ozone. These measures can activate drug molecules, change their surface properties, make them easier to penetrate the skin barrier, effectively kill microorganisms in the cream, improve the hygienic quality of the cream, and reduce the risk of infection. At the same time, the high-voltage pulsed electric field treatment and ozone introduction also help to improve the stability and permeability of the cream, enabling the cream to maintain excellent performance during use.

[0024] In summary, by optimizing the components and preparation process of the cream, the present invention aims to improve the transdermal penetration rate of nadifloxacin cream, enhance its physical stability, and ultimately improve the therapeutic effect of the drug. This technical solution significantly improves the transdermal absorption efficiency of nadifloxacin cream, providing a more effective pharmaceutical preparation for the clinical treatment of skin infections. Detailed implementation manners

[0025] To better understand the technical content of the present invention, specific examples are provided below to further illustrate the present invention.

[0026] Unless otherwise specified, the experimental methods used in the examples of the present invention are all conventional methods.

[0027] Unless otherwise specified, the materials, reagents, etc. used in the examples of the present invention can all be obtained from commercial channels.

[0028] Example 1

[0029] A nadifloxacin cream, wherein the active ingredients include the following raw materials in parts by weight: 40 parts of nadifloxacin raw material medicine, 25 parts of oily matrix, 15 parts of emulsifier, 5 parts of compound penetration enhancer, 5 parts of moisturizer, 3 parts of preservative, and 12 parts of purified water;

[0030] The oily matrix is selected from lard;

[0031] The emulsifier is selected from astragalus gum;

[0032] The moisturizer is glycerol, methylcellulose, and oat β-glucan in a mass ratio of 8:2:1;

[0033] The preservative is selected from phenylmercuric acetate;

[0034] The compound penetration enhancer is baicalein, turmeric, enzyme inhibitor peptide, and withanolide in a mass ratio of 1.5:2.2:8.1:0.2.

[0035] Example 2

[0036] A nadifloxacin cream, wherein the active ingredients include the following raw materials in parts by weight: 60 parts of nadifloxacin raw material medicine, 43 parts of oily matrix, 35 parts of emulsifier, 10 parts of compound penetration enhancer, 12 parts of moisturizer, 6 parts of preservative, and 25 parts of purified water;

[0037] The oily matrix is selected from lanolin;

[0038] The emulsifier is selected from acacia gum;

[0039] The moisturizer is glycerol, methylcellulose, and oat β-glucan in a mass ratio of 15:5:3;

[0040] The preservative is selected from benzalkonium chloride;

[0041] The compound penetration enhancer is baicalein, turmeric, enzyme inhibitor peptide, and withaferin A in a mass ratio of 3.9:5.2:10.6:0.8.

[0042] Example 3

[0043] A nadifloxacin cream, wherein the active ingredients include the following raw materials in parts by weight: 50 parts of nadifloxacin raw material, 35 parts of oily matrix, 25 parts of emulsifier, 8 parts of compound penetration enhancer, 9 parts of humectant, 5 parts of preservative, and 18 parts of purified water;

[0044] The oily matrix is selected from beeswax;

[0045] The emulsifier is selected as PEG-7 olive oil ester;

[0046] The humectant is glycerol, methylcellulose, and oat β-glucan in a mass ratio of 12:4:2;

[0047] The preservative is selected from chlorobutanol;

[0048] The compound penetration enhancer is baicalein, turmeric, enzyme inhibitor peptide, and withaferin A in a mass ratio of 2.7:3.5:9.5:0.5;

[0049] The above Examples 1-3 adopt the following preparation method:

[0050] i), Heat the oily matrix to a molten state at 70°C;

[0051] ii), Add the emulsifier to the oily matrix, mix evenly at a rate of 500 rpm to form an oil-water mixture, and set aside;

[0052] iii), Mix the purified water and the humectant evenly to form a mixed solution, and set aside;

[0053] iv), Gradually add the above oil-water mixture to the mixed solution at a rate of 3 mL / min, and stir with a high-speed shear emulsifier at 2500 rpm while adding until a uniform cream base is formed;

[0054] v), Add the nadifloxacin raw material, compound penetration enhancer, and preservative during the cooling process, stir until completely dissolved and treat intermittently with a high-voltage pulsed electric field 3 times, each time for 3 s. During the treatment process, ozone is simultaneously introduced. The electric field strength of the high-voltage pulsed electric field is 40 kV / cm, the pulse frequency is 400 Hz, the pulse width is 5 μs, and the ozone introduction flow rate is 3 L / min to obtain a uniformly dispersed nadifloxacin cream.

[0055] Example 4

[0056] A nadifloxacin cream, wherein the active ingredients comprise the following raw materials in parts by weight: 50 parts of nadifloxacin raw material medicine, 35 parts of oily matrix, 25 parts of emulsifier, 8 parts of compound penetration enhancer, 9 parts of humectant, 5 parts of preservative, and 18 parts of purified water;

[0057] The oily matrix is selected from beeswax;

[0058] The emulsifier is selected as PEG-7 olive oil ester;

[0059] The humectant is glycerol, methylcellulose, and oat β-glucan with a mass ratio of 12:4:2;

[0060] The preservative is selected from chlorobutanol;

[0061] The compound penetration enhancer is baicalein, turmeric, enzyme inhibitor peptide, and withaferin A with a mass ratio of 2.7:3.5:9.5:0.5;

[0062] The above Example 4 adopts the following preparation method:

[0063] i), Heat the oily matrix to a molten state at 60 °C;

[0064] ii), Add the emulsifier to the oily matrix, and mix evenly at a rate of 400 rpm to form an oil-water mixture for standby;

[0065] iii) Mix the purified water and the humectant evenly to form a mixed solution for standby;

[0066] iv) Gradually add the above oil-water mixture to the mixed solution at a rate of 1 mL / min, and stir with a high-speed shear emulsifier at 2000 rpm while adding, until a uniform cream base is formed;

[0067] v) Add the nadifloxacin raw material, the compound penetration enhancer, and the preservative during the cooling process, stir until completely dissolved, and perform intermittent treatment with high-voltage pulsed electric field 2 times, 1 s each time. During the treatment process, ozone is simultaneously filled. The electric field strength of the high-voltage pulsed electric field is 20 kV / cm, the pulse frequency is 300 Hz, the pulse width is 3 μs, and the ozone filling flow rate is 2 L / min to obtain a uniformly dispersed nadifloxacin cream.

[0068] Example 5

[0069] A nadifloxacin cream, wherein the active ingredients comprise the following raw materials in parts by weight: 50 parts of nadifloxacin raw material medicine, 35 parts of oily matrix, 25 parts of emulsifier, 8 parts of compound penetration enhancer, 9 parts of humectant, 5 parts of preservative, and 18 parts of purified water;

[0070] The oily matrix is selected from beeswax;

[0071] The emulsifier selected is PEG-7 olive oil ester;

[0072] The moisturizer is glycerol, methylcellulose, and oat β-glucan with a mass ratio of 12:4:2;

[0073] The preservative is selected from chlorobutanol;

[0074] The composite penetration enhancer is baicalein, turmeric, enzyme inhibitor peptide, and withaferin A with a mass ratio of 2.7:3.5:9.5:0.5;

[0075] The above Example 5 adopts the following preparation method:

[0076] i), Heat the oily matrix to a molten state at 80 °C;

[0077] ii), Add the emulsifier to the oily matrix and mix evenly at a rate of 600 rpm to form an oil-water mixture for standby;

[0078] iii) Mix purified water and the moisturizer evenly to form a mixed solution for standby;

[0079] iv) Gradually add the above oil-water mixture to the mixed solution at a rate of 5 mL / min, and stir with a high-speed shear emulsifier at 3000 rpm while adding until a uniform cream base is formed;

[0080] v) Add the nadifloxacin raw material, the composite penetration enhancer, and the preservative during the cooling process, stir until completely dissolved and treat with high-voltage pulsed electric field intermittently for 4 times, 5 s each time. During the treatment process, ozone is simultaneously introduced. The electric field strength of the high-voltage pulsed electric field is 50 kV / cm, the pulse frequency is 500 Hz, the pulse width is 8 μs, and the ozone introduction flow rate is 5 L / min to obtain a uniformly dispersed nadifloxacin cream.

[0081] Comparative Example 1

[0082] The difference between this comparative example and Example 3 is that the active ingredients of the nadifloxacin cream include the following raw materials in parts by weight: 30 parts of nadifloxacin raw drug, 13 parts of oily matrix, 40 parts of emulsifier, 3 parts of composite penetration enhancer, 1 part of moisturizer, 8 parts of preservative, and 10 parts of purified water.

[0083] Comparative Example 2

[0084] The difference between this comparative example and Example 3 is that the active ingredients of the nadifloxacin cream do not contain the composite penetration enhancer.

[0085] Comparative Example 3

[0086] The difference between this comparative example and Example 3 is that the composite penetration enhancer of the nadifloxacin cream is menthol and urea with a mass ratio of 1:2.

[0087] Comparative Example 4

[0088] The difference between this comparative example and Example 3 lies in that in the preparation method of the nadifloxacin cream, high-voltage pulsed electric field intermittent treatment is not used in step v); specifically:

[0089] i), Heat the oily matrix to a molten state at 70 °C;

[0090] ii), Add an emulsifier to the oily matrix and mix evenly at a rate of 400 - 600 rpm to form an oil-water mixture for standby;

[0091] iii) Mix purified water and a humectant evenly to form a mixed solution for standby;

[0092] iv) Gradually add the above oil-water mixture to the mixed solution at a rate of 1 - 5 mL / min, and stir with a high-speed shear emulsifier while adding until a uniform cream base is formed;

[0093] v) Add the nadifloxacin raw material, compound penetration enhancer and preservative during the cooling process, stir until completely dissolved, and ultrasonically disperse for 10 min at a temperature of 50 °C and a power of 250 W to obtain a uniformly dispersed nadifloxacin cream.

[0094] I. Transdermal test

[0095] 1. Test purpose: To compare the effects of different cream matrices of the above Examples 1 - 5, Comparative Examples 1 - 4 and commercially available nadifloxacin cream on the transdermal performance of the drug, and to evaluate the in vitro transdermal absorption effect of the drug.

[0096] 2. Test design: The Franz diffusion cell method is adopted, and pig skin is used as a membrane to replace the artificial membrane to simulate the penetration of the drug in the skin;

[0097] 3. Test conditions:

[0098] Number of tests: Each cream preparation is tested at least 6 times;

[0099] Test time: Determined according to the penetration rate of the drug, not exceeding 24 hours at most;

[0100] Test environment: Control the temperature at 32 ± 1 °C and the relative humidity at 60 ± 5% to simulate the actual use conditions.

[0101] 4. Instrument and equipment: Analytical instruments such as a high performance liquid chromatograph (HPLC), as well as a Franz diffusion cell and a constant temperature water bath device.

[0102] 5. Sample preparation: Uniformly coat the above cream on the pig skin test area (3 * 2 cm of the Franz diffusion cell2 ) At a dosage of 100 mg / cm 2 , the receiving solution was taken as the sample solution at 8 h, 12 h, and 24 h respectively, and the cumulative permeation amount of the drug was evaluated by measuring the drug concentration in the receiving solution.

[0103] Cumulative permeation amount calculation formula:

[0104] In the formula: Q n is the cumulative permeation amount (mg / cm 2 ) at the nth sampling, V is the total volume of the receiving solution, V i is the volume (2 mL) of the ith sampling, C i is the drug concentration in the receiving solution measured at the ith sampling, C n is the concentration at the nth sampling point; A is the diffusion and permeation area (cm 2 );

[0105] 6. The test results are as follows:

[0106]

[0107] Result analysis:

[0108] The cumulative permeation amounts of Examples 1 to 5 showed similar trends at the time points of 8 h, 12 h, and 24 h. At 8 h, the cumulative permeation amount ranged from 62.1 - 65.9 mg / cm 2 . By 12 h, the cumulative permeation amount increased to 97.5 - 100.0 mg / cm 2 , showing a relatively high permeation rate, and in Example 3, it had reached 100 mg / cm 2 at 12 h. By 24 h, the cumulative permeation amounts of all examples had reached 100 mg / cm 2 , indicating that the drug in the cream of the example group of the present invention had almost completely permeated through the skin within 24 h.

[0109] The cumulative permeation amounts of Comparative Examples 1 to 4 were significantly lower than those of the examples. At 8 h, the cumulative permeation amount of the comparative examples was 32.6 - 50.3 mg / cm 2 , much lower than 62.1 - 65.9 mg / cm 2 of the examples. By 12 h, the cumulative permeation amount of the comparative examples was 50.9 - 82.1 mg / cm 2 , but still lower than that of the examples. By 24 h, the highest cumulative permeation amount of the comparative examples was 95.4 mg / cm 2 (Comparative Example 1), lower than 100 mg / cm 2 of the examples.

[0110] The cumulative permeation amount of the commercially available cream at 8 hours was 21.9 mg / cm 2 , which was much lower than that of all the examples and most of the comparative examples. By 12 hours, the cumulative permeation amount of the commercially available cream increased to 46.9 mg / cm 2 , but it was still lower than that of the examples and comparative examples. After 24 hours, the cumulative permeation amount of the commercially available cream was 52.8 mg / cm 2 , which was the lowest among all the data, indicating the lowest transdermal absorption efficiency.

[0111] From the above analysis, it can be seen that the cumulative permeation amounts of the examples were significantly higher than those of the comparative examples and the commercially available cream at the time points of 8 hours, 12 hours, and 24 hours. This indicates that the creams in the examples have better transdermal properties, and the drugs can penetrate the skin more effectively. Although the comparative examples also showed certain transdermal effects, they were significantly inferior to the examples. The commercially available cream had the worst transdermal effect, with both the rate and total amount of drug penetration through the skin being low.

[0112] By comparing Example 3 with Comparative Example 1, it can be shown that each component in the cream can affect the viscosity, dispersibility, and stability of the cream through interaction with nadifloxacin, thereby affecting the release and penetration of the drug. Optimizing the ratio of these auxiliary components can improve the permeation performance and stability of the cream;

[0113] By comparing Example 3 with Comparative Examples 2 and 3, at a specific mass ratio, the composite penetration enhancer of the present invention can act synergistically to jointly improve the permeation performance of the cream. Baicalein and curcumin both have good transdermal promoting effects and can increase the skin permeability to the drug; the enzyme inhibitor peptide can inhibit the activity of certain enzymes in the skin and reduce the metabolic degradation of the drug in the skin, thereby improving the transdermal efficiency of the drug; withaferin A has the effect of promoting drug absorption and transdermal penetration. When the four are combined in a certain ratio, they can give full play to their respective advantages and achieve a better transdermal effect;

[0114] By comparing Example 3 with Comparative Example 4, the combined treatment of high-voltage pulsed electric field and ozone can activate the drug molecules, change their surface properties, and make them more easily penetrate the skin barrier. This treatment method can increase the permeability of nadifloxacin molecules, thereby improving the penetration rate of the cream; through the treatment of high-voltage pulsed electric field and ozone, the texture and stability of the cream may be improved, making it easier to apply and absorb. Optimizing the physical properties of the cream can further increase the contact area between the drug and the skin, thereby improving the penetration rate.

[0115] II. Application Test

[0116] The cream obtained in Examples 1-3 was applied to 150 patients with skin infections caused by Propionibacterium acnes, Staphylococcus epidermidis, Gram-positive bacteria, Gram-negative bacteria and anaerobic bacteria, with a male-to-female ratio of 5:3 and an age range of 18-35 years old. The cream was applied every morning and evening for one week.

[0117] Evaluation criteria:

[0118] Significant effect: Symptoms such as skin redness, swelling, pain, and itching are alleviated or disappear, the number of skin lesions such as acne, herpes, and pustules is significantly reduced, and the healing speed is accelerated.

[0119] Effective: Reduces symptoms such as skin redness, swelling, pain, and itching, reduces the number of skin lesions such as acne, herpes, and pustules, and accelerates healing;

[0120] Ineffective: Symptoms such as skin redness, swelling, pain, and itching did not disappear, and skin lesions such as acne, herpes, and pustules did not decrease.

[0121] Evaluation results:

[0122] Number of cases Marked effect Effective Ineffective Total effective rate % Example 1 50 47 2 1 98.0 Example 2 50 42 5 3 94.0 Example 3 50 48 2 0 100.0

[0123] The three embodiments of the present invention all showed good therapeutic effects, especially embodiment 3, which achieved a total effective rate of 100%, indicating that the treatment scheme achieved significant therapeutic effects in most patients.

[0124] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A nadifloxacin cream, characterized in that: The active ingredients include the following raw materials in parts by weight: 40-60 parts of nadifloxacin API, 25-43 parts of oily matrix, 15-35 parts of emulsifier, 5-10 parts of composite penetration enhancer, 5-12 parts of moisturizer, 3-6 parts of preservative, and 12-25 parts of purified water. The composite penetration enhancer is baicalein, turmeric, enzyme inhibitor peptide, and withanolide in a mass ratio of (1.5-3.9):(2.2-5.2):(8.1-10.6):(0.2-0.8); the moisturizer is glycerol, methylcellulose, and oat β-glucan in a mass ratio of (8-15):(2-5):(1-3); The preparation method of the nadifloxacin cream comprises the following steps: i) Heat the oily matrix to a melting state of 60-80°C; ii), adding an emulsifier to the oily base, mixing at a rate of 400-600 rpm to form an oil-water mixture for standby use; iii) mixing the purified water and the moisturizer evenly to form a mixed solution for later use; iv) gradually adding the oil-water mixture into the mixed solution at a rate of 1-5 mL / min, stirring at 2000-3000 rpm using a high-speed shear emulsifier until a uniform cream base is formed; v) adding nafloxacin raw material, composite penetration enhancer and preservative during the cooling process, stirring until completely dissolved and intermittently treating with high-voltage pulse electric field for 2-4 times, each time for 1-5 s, with the electric field strength of the high-voltage pulse electric field being 20-50 kV / cm, the pulse frequency being 300-500 Hz, and the pulse width being 3-8 us, and simultaneously charging ozone during the treatment process at a charging flow rate of 2-5 L / min to obtain a uniformly dispersed nafloxacin cream.

2. A nadifloxacin cream as claimed in claim 1, characterized in that: The active ingredients include the following raw materials in parts by weight: 50 parts of nadifloxacin raw material, 35 parts of oily base, 25 parts of emulsifier, 8 parts of composite penetration enhancer, 9 parts of moisturizer, 5 parts of preservative and 18 parts of purified water.

3. A nadifloxacin cream as claimed in claim 1, characterized in that: The oily matrix is ​​selected from one or more of lard, lanolin, petroleum ether, white vaseline, beeswax, and liquid paraffin.

4. A nadifloxacin cream as claimed in claim 1, characterized in that: The emulsifier is selected from any one of tragacanth gum, gum arabic, Span 80, Span 85, polysorbate 80, sodium lauryl sulfate, poloxamer, and PEG-7 olive oil ester.

5. A nadifloxacin cream as claimed in claim 1, characterized in that: The preservative is selected from any one of phenylmercuric acetate, benzalkonium chloride, benzalkonium bromide, p-hydroxybenzoic acid esters, sodium benzoate, sorbic acid, chlorobutanol, methylparaben, and povidone-iodine.

6. Use of the nadifloxacin cream according to claims 1-5 in the preparation of a medicament for treating skin infection diseases.

7. Use of the nadifloxacin cream as claimed in claim 6 in the preparation of a drug for treating skin infections caused by Propionibacterium acnes, Staphylococcus epidermidis, Gram-positive bacteria, Gram-negative bacteria and anaerobic bacteria.

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