A water-soluble florfenicol powder and a method for preparing the same

Abstract

The application belongs to the technical field of veterinary drug preparation, and particularly relates to a water-soluble florfenicol powder and a preparation method thereof. The water-soluble florfenicol powder is prepared from the following components by weight: florfenicol 20-25 parts, folium isatidis flavones 3-8 parts, a composite dispersion carrier 30-35 parts, hydroxypropyl-beta-cyclodextrin 10-15 parts, a surfactant 6-8 parts, and lactitol 3-5 parts. The water-soluble florfenicol powder prepared by adopting florfenicol and folium isatidis flavones as the effective components and cooperating with specific excipients has high in-vitro dissolution rate, can effectively improve the bioavailability and treatment effect, and has excellent storage stability, and can maintain the drug efficacy and chemical integrity even under long-time storage or specific conditions, and is not prone to degradation or deterioration.

Description

Technical Field

[0001] This invention belongs to the field of veterinary drug preparation technology, specifically relating to a water-soluble florfenicol powder and its preparation method. Background Technology

[0002] Florfenicol (FF), also known as florfenicol, is a broad-spectrum antibacterial drug specifically designed for animals, belonging to the amyl alcohol class of antibiotics. Florfenicol exerts its antibacterial effect by inhibiting bacterial protein synthesis. Specifically, it binds to the 50S subunit of the bacterial 70S ribosome, preventing the activity of peptidyl transferase, thereby inhibiting peptide chain elongation and preventing protein synthesis. This mode of action makes it active against many Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains. Florfenicol is mainly used to treat animal diseases caused by susceptible bacteria, especially in veterinary clinics for the following conditions: Respiratory infections: such as pneumonia and bronchitis in cattle and pigs; Intestinal infections: including yellow and white diarrhea in piglets, E. coli infection and Salmonella infection in chickens; Urogenital infections: such as urinary tract infections and mastitis; Skin and soft tissue infections: such as wound infections and cellulitis; Septicemia and other systemic infections.

[0003] Florfenicol has a broad antibacterial spectrum, wide distribution in the body, good absorption, and no potential aplastic anemia effect. It also has virtually no teratogenic, carcinogenic, or mutagenic properties. Since its introduction in the early 1990s, it has rapidly occupied an important position in the global livestock and poultry farming industry, especially in broiler farming, where its usage rate is as high as 78%.

[0004] Florfenicol is a time-dependent drug, meaning its efficacy depends on the time it takes for blood concentrations to exceed the minimum inhibitory concentration (MIC) rather than the peak concentration. However, it is classified as a Class II drug in biopharmaceutics, meaning it has low solubility but high permeability. This implies that although it is rapidly absorbed after oral or intramuscular injection, its extremely low solubility in water (only about 1.05–1.35 mg / mL) limits drug release and absorption in the gastrointestinal tract, thus affecting bioavailability.

[0005] Therefore, it is necessary to provide a florfenicol drug formulation with high dissolution and bioavailability. Summary of the Invention

[0006] To address the problems existing in the prior art, the present invention aims to provide a water-soluble florfenicol powder and its preparation method. The water-soluble florfenicol powder provided by the present invention uses florfenicol and Isatis indigotica flavonoids as the active pharmaceutical ingredients, which synergistically enhance the overall antibacterial effect. Furthermore, it incorporates excipients such as a composite dispersion carrier composed of DMPC-PLA composite material and methyl methacrylate, hydroxypropyl-β-cyclodextrin, surfactants, and lactitol, which collectively improve drug stability, increase in vitro dissolution and bioavailability, reduce drug waste, and effectively enhance therapeutic efficacy.

[0007] The technical solution of this invention is:

[0008] A water-soluble florfenicol powder is made from the following components in parts by weight:

[0009] Florfenicol 20-25 parts, Isatis indigotica flavonoids 3-8 parts, composite dispersion carrier 30-35 parts, hydroxypropyl-β-cyclodextrin 10-15 parts, surfactant 6-8 parts, lactitol 3-5 parts.

[0010] Furthermore, the flavonoids from Isatis indigotica can be prepared by conventional ethanol extraction. The flavonoids from Isatis indigotica in this invention were purchased from Shaanxi Sinote Biotechnology Co., Ltd.

[0011] Furthermore, the water-soluble florfenicol powder is made from the following components in parts by weight:

[0012] Florfenicol 23 parts, Isatis indigotica flavonoids 6 parts, composite dispersion carrier 33 parts, hydroxypropyl-β-cyclodextrin 12 parts, surfactant 7 parts, lactitol 4 parts.

[0013] Furthermore, the composite dispersion carrier is a composition of DMPC-PLA composite material and methyl methacrylate, wherein the CAS number of methyl methacrylate is 80-62-6.

[0014] Furthermore, the composite dispersion carrier is composed of DMPC-PLA composite material and methyl methacrylate in a weight ratio of 8-10:3-5, preferably 9:4.

[0015] Furthermore, the preparation method of the DMPC-PLA composite material includes the following preparation steps:

[0016] S1. Under nitrogen protection, dissolve polylactic acid (PLA) in dichloromethane, heat to 40-50°C, stir with a magnetic stirrer until completely dissolved, and then store at 4-8°C to obtain a polylactic acid solution for later use.

[0017] S2. Under nitrogen protection, dissolve DMPC in dichloromethane and stir at room temperature until completely dissolved to obtain a DMPC solution for later use.

[0018] S3. Slowly add the dimyristic phosphatidylcholine solution obtained in step S2 to the polylactic acid solution obtained in step S1, stir until fully mixed, and then perform ultrasonic treatment to obtain a mixed solution.

[0019] S4. Transfer the mixed solution obtained in step S3 to a rotary evaporator for rotary evaporation. When a uniform thin film is formed, place it in a vacuum drying oven and dry it at 40-50°C for 16-24 hours. Then grind it into powder to obtain the final product.

[0020] Furthermore, in step S2, the amount of dimyristoylphosphatidylcholine added is 8-15% of the weight of polylactic acid in step S1.

[0021] Furthermore, the polylactic acid has CAS number 26100-51-6 and a molecular weight of 60,000; the dimyristoylphosphatidylcholine has CAS number 18194-24-6.

[0022] Furthermore, in step S1, the ratio of polylactic acid to dichloromethane is 1g:8-10mL.

[0023] Furthermore, in step S2, the ratio of dimyristoylphosphatidylcholine to dichloromethane is 1g:5-10mL.

[0024] Furthermore, the stirring speed in step S3 is 80-150 rpm; the ultrasonic power in step S3 is 30-50 W; and the ultrasonic treatment time is 10-15 min.

[0025] Furthermore, in step S4, the rotation speed of the rotary evaporator is 30-40 rpm, and the temperature is 30-35°C.

[0026] Furthermore, the surfactant is a combination of two of polyethylene glycol and Tween castor oil polyoxyethylene ether.

[0027] Furthermore, the polyethylene glycol is polyethylene glycol 400; the Tween is Tween 80; and the castor oil polyoxyethylene ether is castor oil polyoxyethylene ether EL-40, with CAS number 61791-12-6.

[0028] Furthermore, the surfactant is composed of polyethylene glycol 400 and castor oil polyoxyethylene ether EL-40 in a weight ratio of 1:2 to 3.

[0029] The present invention also provides a method for preparing the water-soluble florfenicol powder, comprising the following preparation steps:

[0030] (1) Add florfenicol and isatis leaf flavonoids to 150-200 parts of mixed solvent, stir well to obtain solution I.

[0031] (2) Take the composite dispersion carrier, hydroxypropyl-β-cyclodextrin, surfactant and lactitol and add them to 300-400 parts of deionized water, mix them evenly at a stirring speed of 300-800 rpm to obtain solution II;

[0032] (3) While stirring, slowly add the solution 1 obtained in step S1 to the solution II obtained in step (2), then homogenize and then spray dry to obtain the solution.

[0033] Further, the mixed solvent in step (1) is a combination of ethanol and ethyl acetate, and the volume ratio of ethanol to ethyl acetate is 1:2; the homogenization pressure in the homogenization process in step (3) is 60-90 MPa, and the homogenization time is 5-10 min.

[0034] Furthermore, in step (3), the particle size of the water-soluble florfenicol powder after spray drying is controlled to be 200-300 μm.

[0035] In addition, the present invention also provides the use of the water-soluble florfenicol powder prepared above in the preparation of veterinary antibacterial drugs.

[0036] Compared with the prior art, the water-soluble florfenicol powder provided by the present invention has the following advantages:

[0037] (1) First, the present invention uses florfenicol and flavonoids from Isatis indigotica as the active ingredients of the drug. The two work synergistically to enhance the overall antibacterial effect and effectively reduce the inflammatory response and oxidative stress caused by infection, which helps to accelerate the recovery process of sick animals and may reduce the side effects during the treatment process.

[0038] (2) In order to better exert the efficacy of florfenicol and flavonoids of Isatis indigotica in this invention and improve their bioavailability, this invention adds excipients such as a composite dispersion carrier composed of DMPC-PLA composite material and methyl methacrylate, hydroxypropyl-β-cyclodextrin, surfactant and lactitol. By highly dispersing the drug in the excipient material, the aggregation state of florfenicol particles is effectively inhibited, and its surface area is greatly increased. When in contact with solvent, the larger the surface area, the faster the dissolution rate. Therefore, the excipients used in this invention can significantly improve the solubility of water-soluble florfenicol powder prepared in this invention in solvent, accelerate the drug dissolution rate, and thus improve its bioavailability and achieve better therapeutic effect.

[0039] (3) Furthermore, the various excipient combinations added in this invention can effectively improve the stability of florfenicol, provide a protective environment for the drug, reduce the contact between the drug and external environmental factors (such as oxygen, light, and humidity), thereby improving the chemical and physical stability of the drug and extending its shelf life.

[0040] (4) Experimental verification shows that the water-soluble florfenicol powder provided by the present invention has a high in vitro dissolution rate, and after accelerated testing, its dissolution rate can still reach more than 94%. Its aqueous solution remains clear, transparent and without precipitation after 24 hours, indicating that the florfenicol powder prepared by the present invention has excellent storage stability. Even under long-term storage or specific conditions, it can still maintain its efficacy and chemical integrity and is not prone to degradation or deterioration. Detailed Implementation

[0041] The present invention will be further described below through specific embodiments, but this is not a limitation of the present invention. Those skilled in the art can make various modifications or improvements based on the basic idea of ​​the present invention, but as long as they do not depart from the basic idea of ​​the present invention, they are all within the protection scope of the present invention.

[0042] Unless otherwise specified, the reagents used in the following examples and comparative examples are conventional reagents, which can be purchased from conventional reagent manufacturers and distributors. Unless otherwise specified, the methods used are existing technologies.

[0043] Example 1

[0044] A water-soluble florfenicol powder is made comprising the following components by weight:

[0045] Florfenicol 20g, Isatis indigotica flavonoids 3g, composite dispersion carrier 30g, hydroxypropyl-β-cyclodextrin 10g, surfactant 6g, lactitol 3g.

[0046] The surfactant is composed of Tween 80 and castor oil polyoxyethylene ether EL-40 in a weight ratio of 1:1.

[0047] The composite dispersion carrier is composed of DMPC-PLA composite material and methyl methacrylate in a weight ratio of 8:5.

[0048] The preparation method of the DMPC-PLA composite material includes the following preparation steps:

[0049] S1. Under nitrogen protection, 100g of polylactic acid (the molecular weight of polylactic acid is 60000) is dissolved in 800mL of dichloromethane, heated to 50°C, and stirred with a magnetic stirrer until completely dissolved. Then, it is refrigerated at 8°C to obtain a polylactic acid solution for later use.

[0050] S2. Under nitrogen protection, dissolve 8g of myristoyl phosphatidylcholine in 40mL of dichloromethane and stir at room temperature until completely dissolved to obtain a myristoyl phosphatidylcholine solution for later use.

[0051] S3. Slowly add the dimyristic phosphatidylcholine solution obtained in step S2 to the polylactic acid solution obtained in step S1, stir at 80 rpm until fully mixed, and then sonicate for 15 min under ultrasonic power of 30 W to obtain a mixed solution.

[0052] S4. Transfer the mixed solution obtained in step S3 to a rotary evaporator and perform rotary evaporation at a speed of 30 rpm and a temperature of 35°C. When a uniform thin film is formed, place it in a vacuum drying oven and dry it at 50°C for 16 hours. Then grind it into powder to obtain the final product.

[0053] The method for preparing the water-soluble florfenicol powder includes the following preparation steps:

[0054] (1) Add florfenicol and flavonoids from Isatis indigotica leaves to 150 mL of mixed solvent and stir until homogeneous to obtain solution I;

[0055] The mixed solvent is composed of ethanol and ethyl acetate in a volume ratio of 1:2;

[0056] (2) Take the composite dispersion carrier, hydroxypropyl-β-cyclodextrin, surfactant and lactitol and add them to 300 mL of deionized water. Mix them evenly at a stirring speed of 300 rpm to obtain solution II.

[0057] (3) While stirring, slowly add the solution 1 obtained in step S1 to the solution II obtained in step (2), homogenize for 10 min under a homogenization pressure of 60 MPa, and then spray dry. After spray drying, control the particle size of the obtained water-soluble florfenicol powder to be 200-300 μm.

[0058] Example 2

[0059] A water-soluble florfenicol powder is made comprising the following components by weight:

[0060] Florfenicol 23g, Isatis indigotica flavonoids 6g, composite dispersion carrier 33g, hydroxypropyl-β-cyclodextrin 12g, surfactant 7g, lactitol 4g.

[0061] The surfactant is composed of polyethylene glycol 400 and castor oil polyoxyethylene ether EL-40 in a weight ratio of 1:2.

[0062] The composite dispersion carrier is composed of DMPC-PLA composite material and methyl methacrylate in a weight ratio of 9:4.

[0063] The preparation method of the DMPC-PLA composite material includes the following preparation steps:

[0064] S1. Under nitrogen protection, 100g of polylactic acid (the molecular weight of polylactic acid is 60000) is dissolved in 900mL of dichloromethane, heated to 45°C, and stirred with a magnetic stirrer until completely dissolved. Then, it is refrigerated at 6°C to obtain a polylactic acid solution for later use.

[0065] S2. Under nitrogen protection, dissolve 10g of myristoyl phosphatidylcholine in 80mL of dichloromethane and stir at room temperature until completely dissolved to obtain a myristoyl phosphatidylcholine solution for later use.

[0066] S3. Slowly add the myristoyl phosphatidylcholine solution obtained in step S2 to the polylactic acid solution obtained in step S1, stir at 120 rpm until fully mixed, and then sonicate for 12 min under ultrasonic power of 40 W to obtain a mixed solution.

[0067] S4. Transfer the mixed solution obtained in step S3 to a rotary evaporator and perform rotary evaporation at a speed of 35 rpm and a temperature of 32°C. When a uniform thin film is formed, place it in a vacuum drying oven and dry it at 45°C for 20 hours. Then grind it into powder to obtain the final product.

[0068] The method for preparing the water-soluble florfenicol powder includes the following preparation steps:

[0069] (1) Add florfenicol and flavonoids from Isatis indigotica leaves to 180 mL of mixed solvent and stir until homogeneous to obtain solution I;

[0070] The mixed solvent is composed of ethanol and ethyl acetate in a volume ratio of 1:2;

[0071] (2) Take the composite dispersion carrier, hydroxypropyl-β-cyclodextrin, surfactant and lactitol and add them to 350 mL of deionized water. Mix them evenly at a stirring speed of 500 rpm to obtain solution II.

[0072] (3) The solution 1 obtained in step S1 is slowly added to the solution II obtained in step (2) while stirring. The solution is homogenized for 8 minutes under a homogenization pressure of 80 MPa, and then spray-dried. After spray drying, the particle size of the water-soluble florfenicol powder is controlled to be between 200 and 300 μm.

[0073] Example 3

[0074] A water-soluble florfenicol powder is made comprising the following components by weight:

[0075] Florfenicol 25g, Isatis indigotica flavonoids 8g, composite dispersion carrier 35g, hydroxypropyl-β-cyclodextrin 15g, surfactant 8g, lactitol 5g.

[0076] The surfactant is composed of polyethylene glycol 400 and castor oil polyoxyethylene ether EL-40 in a weight ratio of 1:3.

[0077] The composite dispersion carrier is composed of DMPC-PLA composite material and methyl methacrylate in a weight ratio of 10:3.

[0078] The preparation method of the DMPC-PLA composite material includes the following preparation steps:

[0079] S1. Under nitrogen protection, 100g of polylactic acid (the molecular weight of polylactic acid is 60000) is dissolved in 1000mL of dichloromethane, heated to 40°C, and stirred with a magnetic stirrer until completely dissolved. Then, it is refrigerated at 4°C to obtain a polylactic acid solution for later use.

[0080] S2. Under nitrogen protection, dissolve 15g of myristoyl phosphatidylcholine in 150mL of dichloromethane and stir at room temperature until completely dissolved to obtain a myristoyl phosphatidylcholine solution for later use.

[0081] S3. Slowly add the myristoyl phosphatidylcholine solution obtained in step S2 to the polylactic acid solution obtained in step S1, stir at 150 rpm until fully mixed, and then sonicate for 10 min under ultrasonic power of 50 W to obtain a mixed solution.

[0082] S4. Transfer the mixed solution obtained in step S3 to a rotary evaporator and perform rotary evaporation at a speed of 40 rpm and a temperature of 30°C. When a uniform thin film is formed, place it in a vacuum drying oven and dry it at 40°C for 24 hours. Then grind it into powder to obtain the final product.

[0083] The method for preparing the water-soluble florfenicol powder includes the following preparation steps:

[0084] (2) Add florfenicol and flavonoids from Isatis indigotica leaves to 200 mL of mixed solvent and stir until homogeneous to obtain solution I;

[0085] The mixed solvent is composed of ethanol and ethyl acetate in a volume ratio of 1:2;

[0086] (2) Take the composite dispersion carrier, hydroxypropyl-β-cyclodextrin, surfactant and lactitol and add them to 400 mL of deionized water. Mix them evenly at a stirring speed of 800 rpm to obtain solution II.

[0087] (3) While stirring, slowly add the solution 1 obtained in step S1 to the solution II obtained in step (2), homogenize for 5 minutes under a homogenization pressure of 90 MPa, and then spray dry. After spray drying, control the particle size of the obtained water-soluble florfenicol powder to be between 200 and 300 μm.

[0088] Comparative Example 1

[0089] The difference from Example 2 is that the DMPC-PLA composite material in the composite dispersion carrier is replaced with polylactic acid (molecular weight 60,000), meaning the composite dispersion carrier is composed of polylactic acid and methyl methacrylate in a weight ratio of 9:4. Other components and preparation methods are the same as in Example 2.

[0090] Comparative Example 2

[0091] The difference from Example 2 is that, in the preparation method of the DMPC-PLA composite material in the composite dispersion carrier, the weight of dimyristoyl phosphatidylcholine in step S2 is increased to 20g, that is, the amount of dimyristoyl phosphatidylcholine added in step S2 is 20% of the weight of polylactic acid in step S1. Other components and preparation methods are the same as in Example 2.

[0092] Comparative Example 3

[0093] The difference from Example 2 is that the castor oil polyoxyethylene ether EL-40 in the surfactant is replaced with fatty alcohol polyoxyethylene ether AEO9 (CAS No.: 68213-23-0), that is, the surfactant is composed of polyethylene glycol 400 and fatty alcohol polyoxyethylene ether AEO9 in a weight ratio of 1:2. Other components and preparation methods are the same as in Example 2.

[0094] Comparative Example 4

[0095] The difference from Example 2 is that the surface activity is only polyethylene glycol 400, that is, the amount of polyethylene glycol 400 used is 5g, and the other components and preparation methods are the same as in Example 2.

[0096] Test Example 1: In Vitro Dissolution Test

[0097] 1. Experimental materials: Water-soluble florfenicol powder prepared in Examples 1-3 and Comparative Examples 1-4 of this invention.

[0098] 2. Experimental methods: The in vitro dissolution rate of a drug is one of the key indicators for evaluating the quality of a drug formulation, and it has a direct impact on the bioavailability and therapeutic effect of the drug.

[0099] In this invention, the dissolution rate (%) of water-soluble florfenicol powder prepared in Examples 1-3 and Comparative Examples 1-4 of this invention was tested for 30 min according to the dissolution test method in Appendix I of the Chinese Veterinary Pharmacopoeia (2020 edition), and the solution state and the solution state after standing for 24 h were recorded. The test results are shown in Table 1.

[0100] Table 1

[0101]

[0102]

[0103] As shown in Table 1, the water-soluble florfenicol powder prepared in Examples 1-3 has a dissolution rate of over 96% within 30 minutes. The dissolved solution is clear and transparent, and no precipitation occurs even after standing at room temperature for 24 hours. This indicates that the water-soluble florfenicol powder prepared in this invention has high dissolution rate and stability in water. Its aqueous solution does not precipitate after standing overnight, which is beneficial for improving the bioavailability of the drug, reducing drug waste, and effectively enhancing the therapeutic effect.

[0104] The dissolution rate of the water-soluble florfenicol powder prepared in Comparative Examples 1 to 4 decreased to varying degrees compared with the data of Examples 1 to 3. Furthermore, after standing for 24 hours, the aqueous solutions of the water-soluble florfenicol powder prepared in Comparative Examples 1 to 4 all showed turbidity and precipitation.

[0105] Test Example 2: Stability Test

[0106] 1. Experimental materials: Water-soluble florfenicol powder prepared in Examples 1-3 and Comparative Examples 1-4 of this invention.

[0107] 2. Test method: The water-soluble florfenicol powder prepared in Examples 1 to 3 and Comparative Examples 1 to 4 of the present invention was placed at a temperature of 40℃±2℃ and a relative humidity of 60%±5% for 3 months. The dissolution rate (%) after 30 minutes was tested and the dissolution state was recorded. The test method was the same as that in Test Example 1.

[0108] Table 2

[0109]

[0110] As shown in Table 2, the water-soluble florfenicol powder prepared in Examples 1-3 of this invention still achieved a dissolution rate of over 94% after three months of accelerated testing. This indicates that the water-soluble florfenicol powder prepared in this invention has excellent stability and can maintain its efficacy and chemical integrity even under long-term storage or specific conditions, and is not prone to degradation or deterioration.

[0111] Trial Example 3: Treatment Efficacy Trial

[0112] 1. Experimental materials: Water-soluble florfenicol powder prepared in Examples 1-3 and Comparative Examples 1-4 of this invention.

[0113] 2. Test methods:

[0114] Two hundred and forty 20-day-old broiler chickens diagnosed with pullorum disease were randomly divided into eight groups: Examples 1-3, Comparative Examples 1-4, and a blank control group, with 30 chickens in each group. Examples 1-3 and Comparative Examples 1-4 were administered the water-soluble florfenicol powder prepared according to Examples 1-3 and Comparative Examples 1-4 of this invention, respectively. The blank control group received no administration. Administration was via drinking water mixing, with 0.8g of the water-soluble florfenicol powder prepared according to Examples 1-3 and Comparative Examples 1-4 dissolved in each liter of water for seven consecutive days. All chickens in each group had the same growing environment and feed.

[0115] The evaluation of therapeutic efficacy is mainly divided into clinical symptoms and prevention and treatment effects. The comprehensive evaluation is categorized as markedly effective, effective, or ineffective. Specifically:

[0116] Effectiveness: At the end of the experiment, the experimental chickens returned to normal mental state and appetite, and there was no diarrhea.

[0117] Effective: At the end of the experiment, the mental state, appetite and diarrhea of ​​the experimental chickens recovered to some extent after treatment.

[0118] Ineffective: After medication, the mental state, appetite, and diarrhea of ​​the experimental chickens were not improved or were lower than those of the blank control group.

[0119] Overall effective rate = (Number of cases with significant effect + Number of cases with effective results) / Number of cases × 100%

[0120] The experimental results are shown in Table 3.

[0121] Table 3

[0122] Group Total number of experiments (units) Effective (only) Valid (only) Invalid (only) Overall effectiveness (%) Blank control group 30 0 0 30 0.0％ Example 1 Group 30 28 1 1 96.7％ Example 2 group 30 28 2 0 100.0％ Example 3 Group 30 29 1 0 100.0％ Comparative Example 1 30 9 13 8 73.3％ Comparative Example 2 30 11 15 4 86.7％ Comparative Example 3 Groups 30 13 12 5 83.3％ Comparative Example 4 Groups 30 14 9 7 76.7％

[0123] As shown in Table 3, the water-soluble florfenicol powder prepared according to this invention has a significant therapeutic effect on pullorum disease in chickens. The total effective rate of groups 1-3 in Examples 1-3 is above 96%, which is significantly higher than that of groups 1-4 in Comparative Examples 1-4. This indicates that the water-soluble florfenicol powder prepared according to this invention effectively improves its bioavailability, thereby improving the therapeutic effect.

[0124] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A water-soluble florfenicol powder, characterized in that, It is made from the following components in parts by weight: Florfenicol 20-25 parts, Isatis indigotica flavonoids 3-8 parts, composite dispersion carrier 30-35 parts, hydroxypropyl-β-cyclodextrin 10-15 parts, surfactant 6-8 parts, lactitol 3-5 parts; The composite dispersion carrier is composed of DMPC-PLA composite material and methyl methacrylate in a weight ratio of 8~10:3~5; The preparation method of the DMPC-PLA composite material includes the following preparation steps: S1. Under nitrogen protection, dissolve polylactic acid (PLA) in dichloromethane, heat to 40~50℃, stir with a magnetic stirrer until completely dissolved, and then store at 4~8℃ to obtain a polylactic acid solution for later use. S2. Under nitrogen protection, dissolve DMPC in dichloromethane and stir at room temperature until completely dissolved to obtain a DMPC solution for later use. S3. Slowly add the dimyristic phosphatidylcholine solution obtained in step S2 to the polylactic acid solution obtained in step S1, stir until fully mixed, and then perform ultrasonic treatment to obtain a mixed solution. S4. Transfer the mixed solution obtained in step S3 to a rotary evaporator for rotary evaporation. When a uniform thin film is formed, place it in a vacuum drying oven and dry it at 40~50℃ for 16~24 h. Then grind it into powder to obtain the final product. In step S2, the amount of myristoyl phosphatidylcholine added is 8-15% of the weight of polylactic acid in step S1. The surfactant is a combination of two of the following: polyethylene glycol, Tween, and castor oil polyoxyethylene ether.

2. The water-soluble florfenicol powder according to claim 1, characterized in that, The water-soluble florfenicol powder is made from the following components in parts by weight: Florfenicol 23 parts, Isatis indigotica flavonoids 6 parts, composite dispersion carrier 33 parts, hydroxypropyl-β-cyclodextrin 12 parts, surfactant 7 parts, lactitol 4 parts.

3. The water-soluble florfenicol powder according to claim 1, characterized in that, In step S1, the ratio of polylactic acid to dichloromethane is 1g:8~10ml; in step S2, the ratio of dimyristoyl phosphatidylcholine to dichloromethane is 1g:5~10mL.

4. The water-soluble florfenicol powder according to claim 1, characterized in that, The stirring speed in step S3 is 80~150 rpm; the ultrasonic power in step S3 is 30~50 W; the ultrasonic treatment time is 10~15 min; the rotation speed of the rotary evaporator in step S4 is 30~40 rpm; and the temperature is 30~35°C.

5. A method for preparing water-soluble florfenicol powder according to any one of claims 1 to 4, characterized in that, The preparation steps include the following: (1) Add florfenicol and flavonoids from Isatis indigotica leaves to 150-200 parts of mixed solvent, stir evenly to obtain solution I; (2) Take the composite dispersion carrier, hydroxypropyl-β-cyclodextrin, surfactant and lactitol and add them to 300-400 parts of deionized water, mix them evenly at a stirring speed of 300-800 rpm to obtain solution II; (3) Add the solution 1 obtained in step S1 slowly to the solution II obtained in step (2) while stirring, then homogenize and then spray dry to obtain the solution.

6. The method for preparing water-soluble florfenicol powder according to claim 5, characterized in that, The mixed solvent in step (1) is a combination of ethanol and ethyl acetate, and the volume ratio of ethanol to ethyl acetate is 1:2; the homogenization pressure in the homogenization process in step (3) is 60~90 MPa, and the homogenization time is 5~10 min.

7. The use of the water-soluble florfenicol powder as described in any one of claims 1 to 4 in the preparation of veterinary antibacterial drugs.

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