Preparation method of florfenicol composite medicine

Abstract

The invention discloses a preparation method of a florfenicol composite drug, and belongs to the technical field of pharmaceutical preparations, the preparation method comprises the following steps: adding florfenicol into a chitosan solution, and attaching the florfenicol to chitosan to form a precursor compound; then an arthrospira sulfated polysaccharide extract is added into the precursor compound, due to the binding force between the arthrospira sulfated polysaccharide extract and chitosan, composite particles coated with florfenicol are formed, and the arthrospira sulfated polysaccharide extract is located on the periphery of the composite particles, so that the composite particles are hydrophilic and carry negative charges; the composite particles coated with the florfenicol are the florfenicol composite medicine. According to the scheme, the use variety of drugs is reduced, the compound drug integrates multiple treatment functions into one drug, the variety of drugs needing to be taken by a patient at the same time is reduced, and the treatment scheme is simplified. According to the scheme, the florfenicol hydrogel has the characteristics of biocompatibility and degradability, the water solubility of florfenicol is improved, the reaction process is very simple, and the florfenicol hydrogel is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a method for preparing a florfenicol compound medicine. Background Art

[0002] Florfenicol, also known as fluorosulfamycin, is a 3-fluorine derivative of sulfamycin and belongs to the new amide antibiotics. It has a broad antibacterial spectrum and excellent pharmacological properties, and has broad application prospects in veterinary clinics. Florfenicol mainly exerts its antibacterial effect by inhibiting bacterial protein synthesis. It binds to the 50S subunit of the bacterial 70S ribosome, preventing the activity of peptidyl transferase, thereby inhibiting the extension of the peptide chain and preventing protein synthesis. Florfenicol is active against many Gram-positive and Gram-negative bacteria, including strains resistant to antibiotics. This makes it have broad application prospects in the treatment of animal diseases caused by sensitive bacteria.

[0003] Florfenicol has the following disadvantages: 1. Florfenicol has the limitation of low solubility in pharmacokinetics, which affects its bioavailability. Florfenicol is a time-dependent drug, and its efficacy depends on the time when the blood concentration exceeds the minimum inhibitory concentration rather than the peak concentration. It is classified as a Class II drug in biopharmaceutics, that is, it has low solubility but high permeability. The extremely low solubility in water limits the release and absorption of drugs in the gastrointestinal tract, thereby affecting bioavailability.

[0004] At present, there are two main ways to improve the water solubility of florfenicol: the first is to develop new types such as florfenicol inclusion compounds from the perspective of pharmacy. However, commonly used encapsulation materials such as hydroxypropyl-β-cyclodextrin cannot increase the efficacy and are difficult to be widely used; the second is to modify and transform the structure of florfenicol, such as making prodrugs such as florfenicol phosphate and florfenicol diacid monoester, which can significantly improve its solubility in water. However, the preparation conditions of these prodrugs are usually harsh and require special reaction conditions and equipment, which increases the difficulty and cost of production, and cannot increase the efficacy, and is difficult to produce industrially. At present, the main therapeutic drug is still florfenicol in its original form (i.e. florfenicol that has not been structurally modified or transformed).

[0005] 2. The disease cycle is often accompanied by complex symptoms, immunodeficiency, complications after treatment, and side effects, especially in the case of mixed bacterial and viral infections, where treatment becomes more complicated. The use of a single drug, such as florfenicol, although effective against some bacterial infections, may not fully cover all pathogens, nor relieve symptoms caused by viruses or other factors.

[0006] In this case, compound drugs with antibacterial and antiviral functions show their unique advantages. By combining multiple active ingredients, these drugs can act on both bacteria and viruses at the same time, thereby alleviating symptoms and improving treatment effects. Summary of the invention

[0007] In view of the deficiencies in the prior art, the present invention provides a method for preparing a florfenicol compound drug.

[0008] A method for preparing a florfenicol composite drug comprises the following steps: firstly, adding florfenicol to a chitosan solution, wherein the florfenicol is attached to the chitosan to form a precursor compound; then, adding an Arthrospira sulfated polysaccharide extract to the precursor compound, and forming composite particles coated with florfenicol due to the binding force between the Arthrospira sulfated polysaccharide extract and the chitosan, wherein the Arthrospira sulfated polysaccharide extract is located on the periphery of the composite particles, so that the composite particles are hydrophilic and negatively charged; the composite particles coated with florfenicol are the florfenicol composite drug.

[0009] A method for preparing a florfenicol compound medicine comprises the following steps: Step S1, preparing Arthrospira sulfated polysaccharide extract solution: At room temperature, dissolve the Arthrospira sulfated polysaccharide extract in deionized water at a concentration of 0.8-1.2 mg / mL, stir evenly, and prepare the Arthrospira sulfated polysaccharide extract solution for later use; Step S2, preparing chitosan solution: At room temperature, chitosan was dissolved in 1 wt% acetic acid with a concentration of 8-12 mg / mL, and then the high-concentration chitosan solution was diluted to a target concentration of 1 mg / mL using phosphate buffered saline, and the pH value was maintained at 5.5-6.5, and the mixture was stirred evenly to obtain a chitosan solution for later use; Step S3, preparing a first solution: Add florfenicol to the chitosan solution and stir evenly to make the weight concentration ratio of chitosan to florfenicol be 1:1, to prepare a first solution for standby use; In the first solution, florfenicol and chitosan are both weakly hydrophobic, and the two combine first to form a precursor complex; Step S4, preparing a second solution: The solution of the sulfated polysaccharide extract of Arthrospira was continuously stirred, and at the same time, the first solution was slowly dripped into the solution of the sulfated polysaccharide extract of Arthrospira, at which time, the concentration of florfenicol was 500 ppm; then, the mixture was mixed evenly to obtain a second solution for standby use; At this time, the weight concentration ratio of chitosan to the sulfated polysaccharide extract of Arthrospira is less than 1.5:1; In the second solution, the chitosan and the sulfated polysaccharide extract of Arthrospira in the precursor complex self-assemble into nanoparticles and load florfenicol to form composite particles.

[0010] A method for preparing a florfenicol compound drug further comprises the following steps: Step S5, centrifuging the second solution: For the second solution, a first precipitate was obtained after centrifugation.

[0011] Step S6, the precipitate is re-added into deionized water to disperse into a suspension, and the suspension is allowed to stand for 1 hour, the supernatant is taken, and the second precipitate is obtained after centrifugation. The second precipitate at this time contains florfenicol composite particles, that is, florfenicol composite drug.

[0012] In step S4, the weight concentration ratio of chitosan, florfenicol and Arthrospira sulfate polysaccharide extracted is 0.75:0.75:1.

[0013] The sulfated polysaccharide extract of Arthrospira has negatively charged sulfate and carboxylic acid groups and a weight average molecular weight of about 272 kDa; chitosan has positively charged amine groups and a number average molecular weight of 1.4×10 5 Da; The weight concentration ratio of chitosan to the sulfated polysaccharide extract of Arthrospira is 0.5~1.5:1. The present invention provides a method for preparing a florfenicol compound drug, which has the following effects: 1. Reduce the types of drugs used: Compound drugs integrate multiple therapeutic functions into one drug, reducing the types of drugs that patients need to take at the same time and simplifying the treatment plan.

[0014] 2. Reduce the risk of drug overdose: When using a single drug, in order to achieve the therapeutic effect, it may be necessary to increase the dosage, which increases the risk of drug overdose. However, compound drugs can reduce the risk of drug overdose while ensuring the efficacy by rationally matching various ingredients.

[0015] 3. Avoid drug conflicts: Different drugs may interact with each other, resulting in weakened or enhanced efficacy, or even adverse reactions. These factors have been taken into account during the development of compound drugs, so conflicts between drugs can be avoided or reduced.

[0016] 4. Ensure the compatibility and stability between various ingredients, BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 Schematic diagram of the structural changes of composite particles at different pH; Figure 2 is the TEM image of the composite particles; Figure 3It is a trend chart of cell survival rate of different concentrations of florfenicol compound drugs. DETAILED DESCRIPTION

[0018] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0019] The sulfated polysaccharide extract of Arthrospira is a highly pure bio-derived polymer with a wide molecular weight distribution and a variable monosaccharide arrangement; the molecular weight distribution is confirmed by high performance size exclusion chromatography with refractive index detection (HPSEC-RI): it is a unimodal distribution with a weight average molecular weight of about 272 kDa, indicating a high degree of homogeneity of the polysaccharide. The sulfated polysaccharide extract of Arthrospira used in this application is a purified sulfated polysaccharide (polysaccharide content of about 99%, weight average molecular weight Mw=272 kDa) extracted from Arthrospira gigantea by pressurized hot water extraction, and is provided by Far East Biotech Co., Ltd. of Taiwan.

[0020] The sulfated polysaccharide extract of Arthrospira has negatively charged sulfate groups and carboxylic acid groups and is a hydrophilic and negatively charged material. This study did not study other types of sulfated polysaccharide extracts, such as the sulfated polysaccharide extract of Spirulina. Since the structural determination of polysaccharides is quite complicated, it is not possible to simply determine that other types of sulfated polysaccharide extracts have the same physicochemical properties as the sulfated polysaccharide extract of Arthrospira. Each sulfated polysaccharide extract may have its own unique biological activity, physical properties and chemical stability, which need to be specifically determined and verified through experiments.

[0021] Arthrospira and Spirulina are two different genera in biological classification. Arthrospira has multicellular filaments that are loosely and regularly curled, usually with a relatively large diameter and large spirals; its typical feature is that its filaments are regularly spiral or wavy. Spirulina has a single filament, often with many filaments gathered to form a thin sheet, which is curved and most of them rotate regularly in a spiral.

[0022] Chitosan is a product of the natural polysaccharide chitin with some acetyl groups removed. It is insoluble in water by itself and must be modified or combined with other materials to improve its hydrophilicity in order to overcome the limitation of its insolubility in water. The chitosan used in this scheme has a number average molecular weight of Mn = 1.4×10 5 Da, purchased from Polymer International Co., Ltd.

[0023] In this scheme, florfenicol is first added to the chitosan solution, and florfenicol is attached to the chitosan to form a precursor complex. Then, the sulfated polysaccharide extract of Arthrospira is added to the precursor complex, and due to the binding force between the sulfated polysaccharide extract of Arthrospira and chitosan, composite particles coated with florfenicol are formed, and the sulfated polysaccharide extract of Arthrospira is located on the periphery of the composite particles, making the composite particles hydrophilic and negatively charged.

[0024] A method for preparing a florfenicol compound drug comprises the following steps: Step S1, preparing Arthrospira sulfated polysaccharide extract solution: At room temperature, dissolve the Arthrospira sulfated polysaccharide extract in deionized water at a concentration of 0.8-1.2 mg / mL, stir evenly, and prepare the Arthrospira sulfated polysaccharide extract solution for later use; Step S2, preparing chitosan solution: At room temperature, chitosan was dissolved in 1wt% acetic acid with a concentration of 8-12 mg / mL, and then the high-concentration chitosan solution was diluted to a target concentration of 1 mg / mL using phosphate buffered saline, and the pH value was maintained at 5.5-6.5 (preferably 6.0), and the mixture was stirred evenly to obtain a chitosan solution for later use; Step S3, preparing a first solution: Add florfenicol to the chitosan solution and stir evenly to make the weight concentration ratio of chitosan to florfenicol be 1:1, to prepare the first solution for later use.

[0025] In the first solution, florfenicol and chitosan are both weakly hydrophobic, and the two are combined first to form a precursor complex.

[0026] Step S4, preparing a second solution: The solution of the sulfated polysaccharide extract of Arthrospira was continuously stirred, and at the same time, the first solution was slowly dripped into the solution of the sulfated polysaccharide extract of Arthrospira, at which time, the concentration of florfenicol was 400-600 ppm (optimally 500 ppm); then, the mixture was mixed at a speed of 800 rpm to obtain a second solution for standby use; At this time, the weight concentration ratio of chitosan to the sulfated polysaccharide extract of Arthrospira is less than 1.5:1; preferably, the weight concentration ratio of chitosan, florfenicol and sulfated polysaccharide extract of Arthrospira is 0.75:0.75:1.

[0027] In the second solution, the chitosan and the sulfated polysaccharide extract of Arthrospira in the precursor complex self-assemble into nanoparticles and load florfenicol to form composite particles.

[0028] Step S5, centrifuging the second solution: The second solution was centrifuged at 2500 rpm for 15 minutes to obtain a first precipitate.

[0029] Step S6, the precipitate is re-added into deionized water to disperse to form a suspension, and the suspension is allowed to stand for 1 hour, the supernatant is taken, and centrifuged at 2500 rpm for 15 minutes to obtain a second precipitate, wherein the precipitate at this time contains florfenicol composite particles, i.e., florfenicol composite drug.

[0030] Steps S5 and S6 are steps for purifying the florfenicol compound drug. In step S5, most of the florfenicol compound drug is centrifuged and precipitated in the form of a first precipitate. In step S6, most of the florfenicol compound drug is suspended in the supernatant and is water-soluble. The supernatant is centrifuged to precipitate the drug, thereby filtering out most of the unreacted raw materials.

[0031] like Figure 1 As shown in the figure, the release behavior of different drugs in different pH media of the composite particles was studied, and the pH-sensitive release characteristics of the composite particles were evaluated. The compound drug showed the best release efficiency under acidic conditions. The sulfated polysaccharide extract of Arthrospira showed stronger negative charge under acidic conditions, which led to the displacement of the site where it binds to the drug, thereby accelerating the release rate of florfenicol. In addition, the conformational change of chitosan made the composite particles sufficiently responsive, because the loosely structured composite particles would accelerate the release of florfenicol due to the swelling effect of chitosan in an acidic environment. The lower release rate in a neutral environment may be attributed to the high stability of the composite, which makes it difficult for structural changes to occur, thereby hindering the release of florfenicol. In addition, under alkaline conditions, the hydrophobic florfenicol and chitosan precursor complex in the composite particles will shrink due to a repulsive reaction with the surrounding alkaline aqueous solution environment. At the same time, the physical properties of the Arthrospira sulfated polysaccharide extract make it more inclined to be close to the environment, which reduces the chance of competing with chitosan binding sites for florfenicol and is therefore not conducive to the diffusion of the drug.

[0032] like Figure 2 As shown, Figure 2 In the figure, Figure A is the TEM image of the composite particles on the 0th day; Figure B is the TEM image of the composite particles immersed in an environment of pH = 4 for 7 days; Figure C is the TEM image of the composite particles immersed in an environment of pH = 7 for 7 days; Figure D is the TEM image of the composite particles immersed in an environment of pH = 10 for 7 days.

[0033] The antiviral evaluation method of florfenicol compound drugs is mainly based on neutralization tests to measure the material's ability to inhibit the pathological effects induced by herpes simplex virus-2 (HSV-2) on Vero cells.

[0034] Experimental purpose: To evaluate the antiviral effect: Through neutralization test, measure the inhibitory ability of continuous concentrations of Spirulina sulfate polysaccharide extract solution, chitosan, and florfenicol compound drug on the HSV-2 virus-induced Vero cell pathological effect.

[0035] The experimental materials are as follows: Cells: Vero cells, each well contains 1×10 4 cells. Virus: HSV-2 virus, plaque forming unit 0.15. Culture medium: Use glucose Dulbecco's modified Eagle's medium supplemented with 2 wt% fetal bovine serum.

[0036] Experimental steps: The density is 1×10 4 Vero cells in 96-well plates were infected with HSV-2 virus and treated with continuous concentrations of Spirulina sulfate polysaccharide extract solution, chitosan, and florfenicol compound drugs.

[0037] The cells were incubated at 37°C for 96 hours.

[0038] Fix the plate by adding 0.5 wt% formaldehyde and incubate at room temperature for 4 h.

[0039] Remove the formaldehyde-fixed plate and stain the wells in the 96-well plate with 0.1 wt % crystal violet for 10 min.

[0040] Wash and air dry the 96-well plate.

[0041] Measure the cell density of each well using a microplate spectrophotometer at 570 nm.

[0042] Data Analysis: Calculate the concentration of Spirulina sulfate polysaccharide extract solution, chitosan, and florfenicol compound required to reduce the virus-induced cytopathic effect by 50%, expressed as EC 50 .

[0043] This program, EC 50 =6.596μg / mL, which is at a relatively low concentration and has good antiviral properties, showing that the composite drug effectively inhibits viruses while protecting cell viability.

[0044] Figure 3 This is a trend chart of cell survival rate of florfenicol compound drugs at different pH concentrations. Figure 3As shown, PBST (PBS buffer containing 5% polysorbate-20) was used at 37°C, and the pH values ​​were set to 4.0, 7.4, and 10.0, respectively. Florfenicol compound drug was added to 75 mL of PBST. The absorbance measured by the microplate spectrophotometer and the weight of florfenicol released into the environmental solution was determined at the predetermined time point using the same calculation method. Figure 3 The release curves under three different pH conditions showed similar trends in the first 12 hours. At pH 7.4, the drug release rate was the fastest in the next 24 hours. However, after 48 hours, the release efficiency in the acidic environment exceeded its release efficiency in the neutral environment. After 168 hours, the release efficiency in the acidic environment reached 27%, which was 5% higher than that in the neutral environment and 10% higher than that in the alkaline environment.

[0045] Florfenicol release rate = (W a / W0)×100%; Among them, W a represents the mass of florfenicol released from the composite particles into the ambient solution at a predetermined time point, and W0 represents the total mass of the florfenicol composite drug.

[0046] This solution has the following features: 1. In this scheme, the sulfated polysaccharide extract of Arthrospira has negatively charged sulfate groups and carboxylic acid groups, while chitosan has positively charged amine groups. Therefore, the binding force of the composite particles formed by the self-assembly of the sulfated polysaccharide extract of Arthrospira and chitosan comes from electrostatic force rather than chemical bonds, and does not change the chemical materials of florfenicol, so the original properties of florfenicol can be retained.

[0047] 2. This application found that the ratio of Arthrospira sulfate polysaccharide extract to chitosan would affect the stability of the composite drug, and conducted an in-depth exploration of the ratio. During the self-assembly process, the hydrophilic and negatively charged Arthrospira sulfate polysaccharide extract encapsulated most of the relatively hydrophobic chitosan to form nanoscale composite particles. However, when chitosan is added in excess, it will lead to an excess of hydrophobic chitosan, thereby destroying the structural stability of the nanoparticles.

[0048] The present application found that when the weight concentration ratio of chitosan to the sulfated polysaccharide extract of Arthrospira reaches 1.5:1, a significant precipitation phenomenon will occur. This phenomenon is attributed to the hydrophobic properties of chitosan; when the chitosan concentration exceeds a certain threshold, even in the presence of hydrophilic sulfated polysaccharide extract of Arthrospira, the suspension stability of the composite particles will be weakened. In addition, as the proportion of chitosan increases, the size of the composite nanoparticles gradually increases, and when the size reaches the micron level, it will trigger the aggregation and precipitation of the composite particles.

[0049] 3. In this application, the size change characteristics of the composite particles under different pH conditions were studied. In particular, in a physiologically neutral environment (pH = 7.4), the morphology and size of the composite particles remained highly stable over an observation period of up to seven days. This finding is in sharp contrast to previous studies, which have shown that composite nanoparticles composed of sulfated polysaccharides (such as heparin) and chitosan often have difficulty maintaining a stable structure when the pH value exceeds 6.5, and are prone to decomposition and collapse. Previous literature pointed out that chitosan will undergo deprotonation in an environment with a pH value greater than 6.5, causing the ionized amino groups on it to gradually lose their positive charge. This reduction in the number of positive charges weakens the ability of chitosan to bind to other materials through electrostatic interactions. However, the composite particles in this scheme showed excellent size and morphological stability when the pH value was higher than 6.5, which is likely due to the unique preparation method of this scheme and the special properties of the selected materials.

[0050] During the preparation process, chitosan is first fully ionized in an environment of about pH 6.0, and then tightly combined with the ionized sulfated polysaccharide extract of Arthrospira under suitable conditions. This preparation strategy forms a stable electrostatic interaction between the sulfated polysaccharide extract of Arthrospira and chitosan, thereby effectively stabilizing the structure of the composite particles. Only under extremely alkaline conditions can the deprotonation of chitosan lead to changes in structural exfoliation.

[0051] In addition, the sulfated polysaccharide extract of Arthrospira itself also has certain swelling properties. Although chitosan may be deprotonated above pH 6.5, the structure of the composite nanoparticles is supported by two polymers, so it can maintain stable size in a neutral environment. In an acidic environment, the main size change of the composite particles can be attributed to the swelling behavior of chitosan under acidic conditions. On the contrary, in an alkaline environment, the size change may be due to the further aggregation caused by the disintegration of the chitosan structure after deprotonation.

[0052] 4. The florfenicol compound drug prepared in this scheme has antiviral effect on the basis of its original antibacterial effect.

[0053] Chitosan itself does not have an effective antiviral effect. Arthrospira sulfate polysaccharide extract exhibits significant antiviral properties due to its rich negative charges, especially the negative charges from the sulfate groups. Arthrospira sulfate polysaccharide extract can interact with virus particles, inhibit their adsorption process, hinder the binding of viruses to cell receptors, prevent viruses from invading host cells, and thus interfere with the life cycle of the virus.

[0054] In addition, due to the complexation of chitosan and Arthrospira sulfated polysaccharide extract, the sulfate groups of Arthrospira sulfated polysaccharide extract will be occupied, indirectly affecting the virus inhibition effect of the composite drug. Despite this, the composite drug still has antiviral properties, which may be related to the core-shell structure: since the Arthrospira sulfated polysaccharide extract is located in the outer shell of the composite particles, and the zeta potential of the composite particles is negative, this means that some of the negatively charged groups of the Arthrospira sulfated polysaccharide extract are not neutralized and are exposed, making it easier to bind to the virus.

[0055] 5. It has biocompatibility and degradability. This solution improves the water solubility of florfenicol, and the reaction process is very simple, which is suitable for industrial production.

[0056] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A method for preparing a florfenicol composite drug, characterized in that: First, florfenicol is added to a chitosan solution, and the florfenicol is attached to the chitosan to form a precursor complex; then, the extract of polysaccharide sulfated from Arthrospira is added to the precursor complex, and due to the binding force between the extract of polysaccharide sulfated from Arthrospira and chitosan, composite particles coated with florfenicol are formed, and the extract of polysaccharide sulfated from Arthrospira is located on the periphery of the composite particles, so that the composite particles are hydrophilic and have a negative charge; the composite particles coated with florfenicol are the florfenicol composite drug.

2. The method for preparing a florfenicol composite drug according to claim 1, wherein: The following steps are involved: Step S1, preparing Arthrospira sulfated polysaccharide extract solution: At room temperature, dissolve the Arthrospira sulfated polysaccharide extract in deionized water at a concentration of 0.8-1.2 mg / mL, stir evenly, and prepare the Arthrospira sulfated polysaccharide extract solution for later use; Step S2, preparing chitosan solution: At room temperature, chitosan was dissolved in 1 wt% acetic acid with a concentration of 8-12 mg / mL, and then the high-concentration chitosan solution was diluted to a target concentration of 1 mg / mL using phosphate buffered saline, and the pH value was maintained at 5.5-6.5, and the mixture was stirred evenly to obtain a chitosan solution for later use; Step S3, preparing a first solution: Add florfenicol to the chitosan solution and stir evenly to make the weight concentration ratio of chitosan to florfenicol be 1:1, to prepare a first solution for standby use; In the first solution, florfenicol and chitosan are both weakly hydrophobic, and the two combine first to form a precursor complex; Step S4, preparing a second solution: The solution of the sulfated polysaccharide extract of Arthrospira was continuously stirred, and at the same time, the first solution was slowly dripped into the solution of the sulfated polysaccharide extract of Arthrospira, at which time, the concentration of florfenicol was 500 ppm; then, the mixture was mixed evenly to obtain a second solution for standby use; At this time, the weight concentration ratio of chitosan to the sulfated polysaccharide extract of Arthrospira is less than 1.5:1; In the second solution, the chitosan and the sulfated polysaccharide extract of Arthrospira in the precursor complex self-assemble into nanoparticles and load florfenicol to form composite particles.

3. The method for preparing a florfenicol composite drug according to claim 2, wherein: The following steps are also included: Step S5, centrifuging the second solution: For the second solution, a first precipitate is obtained after centrifugation; Step S6, the precipitate is re-added into deionized water to disperse into a suspension, and the suspension is allowed to stand for 1 hour, the supernatant is taken, and the second precipitate is obtained after centrifugation. The second precipitate at this time contains florfenicol composite particles, that is, florfenicol composite drug.

4. The method for preparing a florfenicol composite drug according to claim 3, wherein: In step S4, the weight concentration ratio of chitosan, florfenicol and Arthrospira sulfate polysaccharide extracted is 0.75:0.75:

1.

5. The method for preparing a florfenicol composite drug according to claim 3, characterized in that: The sulfated polysaccharide extract of Arthrospira has negatively charged sulfate and carboxylic acid groups and a weight average molecular weight of about 272 kDa; chitosan has positively charged amine groups and a number average molecular weight of 1.4×10 5 Da; The weight concentration ratio of chitosan to the sulfated polysaccharide extract of Arthrospira is 0.5~1.5:1.

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