Medicament for preventing and treating chicken mycoplasma synoviae and preparation method thereof

Abstract

The invention relates to the technical field of veterinary drugs, and provides a medicament for preventing and treating chicken mycoplasma synoviae and a preparation method thereof.The medicament is prepared from, by weight, 40-50 parts of nanometer material modified doxycycline, 30-40 parts of glucose, 2-3 parts of sodium chloride, 1.5-2.5 parts of sodium dihydrogen phosphate, 5-8 parts of antioxidant, 1-2 parts of preservative and 0.5-1.5 parts of silicon dioxide. The medicament product disclosed by the invention is stable in quality, various indexes are not influenced, the doxycycline is modified so that the medicament product has a slow release effect, the bitter taste of the doxycycline is reduced, the compliance of chickens is improved, the stress reaction of the chickens is reduced, the bioavailability is high, the treatment effect on the mycoplasma synoviae of the chickens is good, and the medicament product has a better market value.

Description

Technical Field

[0001] The invention belongs to the technical field of veterinary drugs, and particularly relates to a medicament for preventing and treating chicken synoviae mycoplasma disease and a preparation method thereof. Background Art

[0002] As the poultry industry develops towards scale, chickens are often kept in a relatively dense space. If there are omissions in feeding management, poor environmental conditions, or the breeder chickens are not effectively purified of pathogens, the flocks are easily infected with synoviae, a disease that has posed a serious threat to the health of the flocks in recent years. Synoviae can cause poultry to be listless, feathers to lose their luster, joints to become inflamed and swollen, and accompanied by a large amount of fluid accumulation, making it difficult to walk and stand unsteadily, affecting their normal eating and drinking, and then causing them to become emaciated due to long-term malnutrition, growth and development to be hindered, production performance to be reduced, and they may eventually die of exhaustion. This disease has caused serious economic losses to the poultry farming industry. Therefore, the prevention and treatment of synoviae cannot be ignored.

[0003] In actual production and breeding, if chickens are infected with mycoplasma diseases, they are often treated with antibiotics such as aminoglycosides, tetracyclines, macrolides and amides. Among them, one of the preferred antibiotics is doxycycline. However, doxycycline tastes bitter and has a strong irritating effect on the upper digestive tract, which greatly limits the compliance of livestock and poultry in taking medicine. At the same time, in order to improve compliance, many manufacturers have made antibiotics into injections, but when chickens are infected, injecting drugs greatly increases labor costs.

[0004] Chinese patent CN 111789883 B discloses a new type of sustained-release injection of traditional Chinese medicine, a preparation method and its application in treating poultry synovial mycoplasma disease. The weight composition of each 100g of the injection is: 0.01-2g of dentamisol, 0.01-5g of forsythia phenol, 10-40g of Tween 80, and 407-15g of poloxamer. 0.5-10g, behenic acid glyceryl 0.1-8g, ethyl oleate 1-16g, 1,2-propylene glycol 5-10g, and the balance is deionized water. The sustained-release injection of this invention is a double continuous phase emulsion, the main component of which is a Chinese medicine extract. It will not cause food safety problems due to drug residues. After injection, it can slowly release the drug locally in the tissue to play a long-lasting effect. As an injectable drug, it avoids the problem of poor compliance caused by the bitter taste while ensuring the efficacy. However, for large-scale farms, if they want to use this drug, the labor cost will be greatly increased. Catching chickens and injecting them are not only time-consuming and labor-intensive, but may also cause stress reactions in chickens.

[0005] Therefore, there is an urgent need to develop a drug for preventing and treating chicken synoviae mycoplasma disease, which not only has stable product quality but also can improve compliance, avoid stress response, and achieve good therapeutic effects. Summary of the invention

[0006] In view of the existing technical problems, the purpose of the present invention is to provide a medicament for preventing and treating chicken synoviae mycoplasma disease and a preparation method thereof. The medicament product of the present invention has stable quality, and various indicators are not affected. The doxycycline is modified to have a sustained release effect, and its bitterness is reduced, the compliance of chickens is improved, the stress response of chickens is reduced, the bioavailability is high, the therapeutic effect on chicken synoviae mycoplasma disease is good, and it has a good market value.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] On one hand, the present invention provides a medicament for preventing and treating chicken synoviae mycoplasma disease, which comprises the following raw materials by weight: 40-50 parts of nanomaterial-modified doxycycline, 30-40 parts of glucose, 2-3 parts of sodium chloride, 1.5-2.5 parts of sodium dihydrogen phosphate, 5-8 parts of antioxidant, 1-2 parts of preservative and 0.5-1.5 parts of silicon dioxide.

[0009] The reaction mechanism and effects of the present invention are as follows:

[0010] 1. Doxycycline is a broad-spectrum antibiotic belonging to the tetracycline class. It has a strong antibacterial effect and can effectively fight against a variety of bacteria. In the prevention and treatment of chicken synovia mycoplasma disease, doxycycline can be used as a highly effective antibiotic. The present invention utilizes the condensation of proanthocyanidin B2-3"-O-gallate, 3,4-dihydroxybenzaldehyde, formaldehyde and 1,2,3-triaminoguanidine. At the same time, the intermolecular hydrogen bonds and π-π stacking forces increase the entanglement and interaction between oligomer molecules, causing the oligomers to self-assemble into nanomaterials with antioxidant and therapeutic effects. The applicant mixes the nanomaterial with doxycycline by controlling a specific ratio to form nanomaterial-modified doxycycline.

[0011] On the one hand, the introduction of nanomaterials can increase the dispersibility of doxycycline, facilitate the absorption and distribution of the drug in the body, and improve its bioavailability; at the same time, nanomaterials can control the release rate of the drug, achieve a sustained-release effect, prolong the duration of drug action, and reduce the frequency of administration.

[0012] On the other hand, the three-dimensional structure of the biofilm increases the resistance of bacteria to traditional antibiotic treatment and host immune response, leading to enhanced bacterial resistance. The positively charged guanidine functional groups of the present invention are densely distributed on the surface of the nanoparticles to improve the binding ability of the nanoparticles with the bacterial cell membrane and the penetration ability to the biofilm, which can effectively kill the bacteria wrapped in the biofilm, and cooperate with doxycycline to remove the mycoplasma and bacteria that cause the chicken synovial bursa, thereby improving the cure rate.

[0013] In addition, the introduction of nanomaterials can avoid the bitter taste of doxycycline and improve the compliance of chickens.

[0014] 2. During storage, transportation and use, doxycycline may produce isomers under the action of light. This phenomenon will make the drug properties of doxycycline unstable, and antioxidants need to be added to maintain the stability of the drug.

[0015] Flavonoids (5,7-dihydroxyflavone) are natural compounds with a wide range of pharmacological effects, but due to the poor water solubility and fat solubility of 5,7-dihydroxyflavone, its intestinal absorption is very low, limiting its application. Therefore, the present application modifies the structure of 5,7-dihydroxyflavone for the purpose of improving anti-oxidation and anti-inflammatory properties. The present invention uses 5,7-dihydroxyflavone and 1,2-dibromoethylbenzene to form an intermediate product, which is then mixed with methyl gallate to form an antioxidant to improve its compatibility, which not only helps to inhibit the growth of bacteria, but also effectively improves the antioxidant properties of the agent, and protects doxycycline from oxidation by capturing free radicals and inhibiting oxidation reactions, thereby maintaining the chemical stability and biological activity of the agent.

[0016] In some embodiments, the method for preparing the nanomaterial-modified doxycycline comprises the following steps:

[0017] S1. Mix 1,2,3-triaminoguanidine and sodium hydroxide aqueous solution to obtain solution 1 for later use; dissolve proanthocyanidin B2-3"-O-gallate, 3,4-dihydroxybenzaldehyde and formaldehyde aqueous solution in deionized water and stir to obtain solution 2 for later use;

[0018] S2. adding the solution 1 obtained in step S1 to the solution 2, reacting for 1-2 hours, collecting the nanoparticles by centrifugation, purifying, resuspending in deionized water, and storing at 2-8° C. to obtain a nanomaterial;

[0019] S3. Disperse the nanomaterial and doxycycline obtained in step S2 in deionized water, perform ultrasonic stirring, and dry to obtain nanomaterial-modified doxycycline.

[0020] In some embodiments, the mass ratio of proanthocyanidin B2-3″-O-gallate and 1,2,3-triaminoguanidine in step S1 is (2-3):1.

[0021] In some embodiments, the mass ratio of the nanomaterial to doxycycline in step S3 is (1.5-3.5):1.

[0022] Preferably, the mass ratio of proanthocyanidin B2-3″-O-gallate to 3,4-dihydroxybenzaldehyde in step S1 is (4.5-6):1.

[0023] In some embodiments, the method for preparing the antioxidant comprises the following steps:

[0024] (1) Add 5,7-dihydroxyflavone, potassium carbonate and acetone to a reaction kettle, heat and stir under reflux until the solution becomes clear, add a mixed solution of 1,2-dibromoethylbenzene and acetone dropwise, heat and condense under reflux, react for 2-4 hours, filter, add water to the filtrate to precipitate solids, filter, wash, and vacuum dry to obtain an intermediate product;

[0025] (2) dissolving gallic acid in methanol, adding thionyl chloride dropwise in an ice bath, heating in an oil bath to condense and reflux for 4-6 hours after the addition is complete, and distilling under reduced pressure to obtain methyl gallate;

[0026] (3) dissolving the methyl gallate obtained in step (2) in N,N-dimethylformamide, adding potassium carbonate, stirring for 5-15 minutes, adding the intermediate product obtained in step (1) and tetrabutylammonium bromide, heating and stirring to react for 4-6 hours, extracting with ethyl acetate, washing the obtained organic layer with saturated sodium chloride, then drying with anhydrous sodium sulfate, and separating by silica gel column chromatography to obtain an antioxidant.

[0027] In some embodiments, the molar ratio of 5,7-dihydroxyflavone to 1,2-dibromoethylbenzene in step (1) is 1:(3-5).

[0028] In some embodiments, the molar ratio of methyl gallate to the intermediate product in step (3) is (4-5):1.

[0029] Preferably, the eluent for silica gel column chromatography separation is ethyl acetate and petroleum ether in a volume ratio of 1:3.

[0030] In some embodiments, the preservative is phenoxyethanol and / or parabens.

[0031] In some embodiments, the silica has a particle size of 800-1200 mesh.

[0032] Preferably, the particle size of the silicon dioxide is 1000-1200 mesh.

[0033] Another aspect of the present invention provides a method for preparing a medicament for preventing and treating chicken synoviae mycoplasma disease, comprising the following steps:

[0034] The nanomaterial-modified doxycycline, glucose, sodium chloride, sodium dihydrogen phosphate, antioxidant, preservative and silicon dioxide are mixed and stirred for 1-2 hours, and dried to obtain a medicine.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] 1. The pharmaceutical product of the present invention has stable quality, and various indicators are not affected. The doxycycline is modified to have a sustained-release effect, while reducing its bitterness, improving the compliance of chickens, reducing the stress response of chickens, having high bioavailability, and having a good therapeutic effect on chicken synoviae mycoplasma disease, and having a better market value.

[0037] 2. The nanomaterial-modified doxycycline of the present invention has good efficacy. On the one hand, it can increase the dispersibility of doxycycline and improve bioavailability; at the same time, the nanomaterial can achieve a sustained release effect, prolong the drug's action time, and reduce the frequency of administration. On the other hand, the positively charged guanidine functional groups of the present invention are densely distributed on the surface of the nanoparticles, which can effectively kill bacteria wrapped in biofilms, and cooperate with doxycycline to remove mycoplasmas and bacteria that cause chicken synovial bursae, thereby improving the cure rate. In addition, the introduction of nanomaterials can avoid the bitter taste of doxycycline and improve the compliance of chickens.

[0038] 3. The antioxidant of the present invention has good compatibility and is conducive to intestinal absorption. It not only helps to inhibit the growth of bacteria, but also effectively improves the antioxidant properties of the agent. DETAILED DESCRIPTION

[0039] The present invention will be described below in conjunction with specific embodiments. It should be noted that the following embodiments are examples of the present invention and are only used to illustrate the present invention, rather than to limit the present invention. Other combinations and various modifications within the concept of the present invention may be performed without departing from the spirit or scope of the present invention.

[0040] Each medicine was prepared according to the ratio of each raw material and the preparation method specified in the following examples and comparative examples.

[0041] In order to facilitate those skilled in the art to implement the present invention, some raw material manufacturers of the embodiments and comparative examples are described as follows:

[0042] Silicon dioxide: particle size is 1000 mesh;

[0043] Other raw materials are not specially specified and can be purchased from the market.

[0044] Preparation Example 1

[0045] The preparation method of nanomaterial-modified doxycycline A comprises the following steps:

[0046] S1. 16 mg 1,2,3-triaminoguanidine and 150 μL 0.25 mol / L sodium hydroxide aqueous solution were mixed to obtain solution 1 for standby use; 40 mg proanthocyanidin B2-3"-O-gallate, 8 mg 3,4-dihydroxybenzaldehyde, and 16 ml 37 wt% formaldehyde aqueous solution were dissolved in 10 ml deionized water and stirred for 1.5 h to obtain solution 2 for standby use;

[0047] S2. Add solution 1 obtained in step S1 to solution 2, react for 2 h, centrifuge at 14000 r / min for 3 min, collect nanoparticles, purify with secondary water five times, resuspend in 2 ml of deionized water, and store at 5° C. for later use to obtain nanomaterials;

[0048] S3. Disperse 25 mg of the nanomaterial obtained in step S2 and 10 mg of doxycycline in 40 ml of deionized water, stir ultrasonically for 45 min, and dry at 60° C. for 4 h to obtain nanomaterial-modified doxycycline A.

[0049] Preparation Example 2

[0050] The preparation method of nanomaterial-modified doxycycline B is the same as that of Preparation Example 1, except that the mass of added proanthocyanidin B2-3″-O-gallate is 28.8 mg.

[0051] Preparation Example 3

[0052] The preparation method of nanomaterial-modified doxycycline C comprises the following steps:

[0053] The preparation method of nanomaterial-modified doxycycline C is the same as that in Preparation Example 1, except that the mass of the added nanomaterial is 13 mg.

[0054] Preparation Example 4

[0055] The preparation method of antioxidant A comprises the following steps:

[0056] (1) 10 mmol 5,7-dihydroxyflavone, 5 mmol potassium carbonate, and 150 ml acetone were added to a reaction kettle, heated to 35°C, stirred and refluxed until the solution became clear, and a mixed solution of 40 mmol 1,2-dibromoethylbenzene and 10 ml acetone was added dropwise, heated to 45°C, condensed and refluxed, reacted for 3 h, filtered, 0°C ice water was added to the filtrate to precipitate solids, filtered to obtain solids, washed with ethanol three times, and vacuum dried at 50°C for 2 h to obtain an intermediate product;

[0057] (2) Dissolve 10 mmol of gallic acid in 30 ml of methanol, add 1 ml of thionyl chloride dropwise in an ice bath at 0°C, heat in an oil bath and reflux for 5 h, and remove the solvent by distillation under reduced pressure to obtain methyl gallate;

[0058] (3) Dissolve 5 mmol of methyl gallate obtained in step (2) in 10 ml of N,N-dimethylformamide, add 2 mmol of potassium carbonate, stir for 10 min, add 1 mmol of the intermediate product obtained in step (1) and 0.1 mmol of tetrabutylammonium bromide, heat to 60° C., stir for 5 h, extract with ethyl acetate, wash the obtained organic layer with saturated sodium chloride three times, then dry with anhydrous sodium sulfate for 4 h, separate by silica gel column chromatography, and use ethyl acetate and petroleum ether in a volume ratio of 1:3 as the eluent to obtain antioxidant A.

[0059] Preparation Example 5

[0060] The preparation method of antioxidant B is the same as that of Preparation Example 4, except that the amount of 1,2-dibromoethylbenzene added is 28 mmol.

[0061] Preparation Example 6

[0062] The preparation method of antioxidant C is the same as that of Preparation Example 4, except that the amount of methyl gallate added is 3.8 mmol.

[0063] Example 1

[0064] A medicament for preventing and treating chicken synoviae mycoplasma disease comprises the following raw materials by weight: 45 parts of nanomaterial-modified doxycycline A, 35 parts of glucose, 2.5 parts of sodium chloride, 2 parts of sodium dihydrogen phosphate, 6.5 parts of antioxidant A, 1.5 parts of phenoxyethanol and 1 part of silicon dioxide.

[0065] The preparation method of the medicine of this embodiment comprises the following steps:

[0066] The nanomaterial-modified doxycycline A, glucose, sodium chloride, sodium dihydrogen phosphate, antioxidant A, phenoxyethanol, and silicon dioxide were mixed and stirred for 1.5 hours, and dried at 50° C. for 2 hours to obtain a drug.

[0067] Example 2

[0068] A medicament for preventing and treating chicken synoviae mycoplasma disease comprises the following raw materials by weight: 40 parts of nanomaterial-modified doxycycline A, 30 parts of glucose, 2 parts of sodium chloride, 1.5 parts of sodium dihydrogen phosphate, 5 parts of antioxidant A, 1 part of phenoxyethanol, and 0.5 parts of silicon dioxide.

[0069] The preparation method of the medicament of this embodiment comprises the following steps:

[0070] The nanomaterial-modified doxycycline A, glucose, sodium chloride, sodium dihydrogen phosphate, antioxidant A, phenoxyethanol and silicon dioxide were mixed and stirred for 1 hour, and dried at 50° C. for 2 hours to obtain a medicine.

[0071] Example 3

[0072] A medicament for preventing and treating chicken synoviae mycoplasma disease comprises the following raw materials in parts by weight: 50 parts of nanomaterial-modified doxycycline A, 40 parts of glucose, 3 parts of sodium chloride, 2.5 parts of sodium dihydrogen phosphate, 8 parts of antioxidant A, 2 parts of phenoxyethanol, and 1.5 parts of silicon dioxide.

[0073] The preparation method of the medicament of this embodiment comprises the following steps:

[0074] The nanomaterial-modified doxycycline A, glucose, sodium chloride, sodium dihydrogen phosphate, antioxidant A, phenoxyethanol and silicon dioxide were mixed and stirred for 2 hours, and dried at 50° C. for 2 hours to obtain a medicine.

[0075] Example 4

[0076] A medicament for preventing and treating chicken synoviae mycoplasma disease and a preparation method thereof. The specific implementation manner is the same as that of Example 1, except that an equal amount of nanomaterial-modified doxycycline B is used to replace nanomaterial-modified doxycycline A.

[0077] Example 5

[0078] A medicament for preventing and treating chicken synoviae mycoplasma disease and a preparation method thereof. The specific implementation manner is the same as that of Example 1, except that an equal amount of nanomaterial-modified doxycycline C is used to replace nanomaterial-modified doxycycline A.

[0079] Example 6

[0080] A medicament for preventing and treating chicken synoviae mycoplasma disease and a preparation method thereof. The specific implementation manner is the same as that of Example 1, except that an equal amount of antioxidant B is used to replace antioxidant A.

[0081] Example 7

[0082] A medicament for preventing and treating chicken synoviae mycoplasma disease and a preparation method thereof. The specific implementation manner is the same as that of Example 1, except that an equal amount of antioxidant C is used to replace antioxidant A.

[0083] Example 8

[0084] A medicament for preventing and treating chicken synoviae mycoplasma disease and a preparation method thereof. The specific implementation manner is the same as that of Example 1, except that an equal amount of methyl gallate is used to replace antioxidant A.

[0085] Comparative Example 1

[0086] A medicament for preventing and treating chicken synoviae mycoplasma disease and a preparation method thereof, wherein the specific implementation manner is the same as that of Example 1, except that an equal amount of doxycycline is used to replace the nanomaterial-modified doxycycline A.

[0087] Effect evaluation:

[0088] The pharmaceutical preparations prepared in the above Examples 1-8 and Comparative Example 1 were tested and analyzed, and the specific results are shown in Table 1.

[0089] Performance Test:

[0090] (1) Toxicity test:

[0091] ①Acute toxicity test:

[0092] The prepared drug was fed to mice (9 groups in total, 3 mice in each group), with the maximum dosage of 4 g / kg each time, three times a day, and a total dosage of 6 g / kg. No adverse reactions were found in the mice.

[0093] ② Subacute toxicity test: 90 rats weighing 50-70g were selected and randomly divided into 9 groups, with 20 rats in each group (half male and half female). Each rat was fed with the drug at 0.6g / day, twice a day. After 90 days of administration, all test indicators were normal, and pathological examination of the animal organs and tissues showed no pathological changes caused by the drug.

[0094] As can be seen from the above, both the acute toxicity test and the subacute toxicity test can illustrate that the medicament of the present invention has no toxic side effects.

[0095] (2) 180 sick chickens weighing about 2±0.5kg, with clinical symptoms of joint swelling, difficulty walking, decreased food intake, and similar overall disease severity were randomly selected from a chicken farm with synoviae infection. These chickens were randomly divided into 9 groups, with 20 chickens in each group. The medicaments prepared in the embodiments and comparative examples were stored at 35°C for 1 month and then diluted with water for continuous feeding for 7 days, with 100mg of medicament diluted with 100kg of water. During the test, the behavior, feeding recovery and mortality of the chickens in each group were observed every day. The results are shown in Table 1.

[0096] Criteria for judging efficacy results:

[0097] ① Cured: After taking the medicine, lameness, lying down, swollen joints, etc. are significantly improved, and the chickens can walk normally. The symptom improvement rate is more than 80%. The chickens' ruffled feathers, white crowns, and emaciation symptoms basically disappear, and the recurrence rate is <20% 21 days after taking the medicine.

[0098] ② Significant effect: After taking the medicine, lameness, lying down, swollen joints, etc. are significantly improved, and the chickens can walk normally. The symptom improvement rate is between 30-80%. The chickens' ruffled feathers, white crowns, and emaciation symptoms basically disappear, and the recurrence rate is between 20-60% 21 days after taking the medicine.

[0099] ③ Ineffective: After taking the medicine, lameness, lying down, swollen joints, etc. are significantly improved, and the chickens can walk normally. The symptom improvement rate is less than 30%. The chickens' ruffled feathers, white crowns, and emaciation symptoms basically disappear. The recurrence rate is >60% 21 days after taking the medicine. Chickens that died during the medication process are considered ineffective.

[0100] Test results:

[0101] Cure rate (%) = number of cured chickens / number of chickens in each group * 100%;

[0102] Effective rate (%) = number of effective chickens / number of chickens in each group*100%;

[0103] Inefficiency (%) = number of ineffective chickens / number of chickens in each group*100%;

[0104] Total effective rate (%) = cure rate + effective rate.

[0105] Table 1

[0106] Serial number Cure rate / % Effectiveness / % Inefficiency / % Total effective rate / % Example 1 75 20 5 95 Example 2 70 20 10 90 Example 3 70 25 5 95 Example 4 65 20 15 85 Example 5 60 15 25 75 Example 6 65 20 15 85 Example 7 65 15 20 80 Example 8 60 20 20 80 Comparative Example 1 55 15 30 70

[0107] It can be seen from the results in Table 1 that the medicaments prepared in Examples 1-3 have a higher cure rate.

[0108] Compared with Example 1, when preparing nanomaterial-modified doxycycline, Example 4-5 changes the mass ratio of proanthocyanidin B2-3"-O-gallate and 1,2,3-triaminoguanidine, and the antioxidant activity of the nanomaterial is weakened. Example 5 changes the mass ratio of the nanomaterial and doxycycline, and the sustained-release effect is weakened. Comparative Example 1 uses an equal amount of doxycycline to replace the nanomaterial-modified doxycycline A, and the dispersibility of doxycycline is poor, thereby reducing the bioavailability of doxycycline and affecting the therapeutic effect.

[0109] Compared with Example 1, when preparing the antioxidant, Example 6-7 changes the molar ratio of 5,7-dihydroxyflavone and 1,2-dibromoethylbenzene, and Example 7 changes the molar ratio of methyl gallate and the intermediate product, both of which make the compatibility of the antioxidant worse. Example 8 replaces antioxidant A with an equal amount of methyl gallate, which makes the antioxidant property of the agent poor, thereby causing the chemical stability and biological activity of the agent to decrease, further affecting the therapeutic effect.

[0110] The above is only a preferred embodiment of the present invention and does not constitute any form of limitation to the present application. Although the present application is disclosed as above in the preferred embodiment, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution.

Claims

1. A medicament for preventing and treating chicken synoviae mycoplasma disease, characterized in that: The invention comprises the following raw materials by weight: 40-50 parts of nano-material modified doxycycline, 30-40 parts of glucose, 2-3 parts of sodium chloride, 1.5-2.5 parts of sodium dihydrogen phosphate, 5-8 parts of antioxidant, 1-2 parts of preservative and 0.5-1.5 parts of silicon dioxide.

2. The agent for preventing and treating chicken synoviae mycoplasma disease according to claim 1, characterized in that: The preparation method of the nanomaterial-modified doxycycline comprises the following steps: S1. Mix 1,2,3-triaminoguanidine and sodium hydroxide aqueous solution to obtain solution 1 for later use; dissolve proanthocyanidin B2-3"-O-gallate, 3,4-dihydroxybenzaldehyde and formaldehyde aqueous solution in deionized water and stir to obtain solution 2 for later use; S2. adding the solution 1 obtained in step S1 to the solution 2, reacting for 1-2 hours, collecting the nanoparticles by centrifugation, purifying, resuspending in deionized water, and storing at 2-8° C. to obtain a nanomaterial; S3. Disperse the nanomaterial and doxycycline obtained in step S2 in deionized water, perform ultrasonic stirring, and dry to obtain nanomaterial-modified doxycycline.

3. The agent for preventing and treating chicken synoviae mycoplasma disease according to claim 2, characterized in that: The mass ratio of proanthocyanidin B2-3″-O-gallate and 1,2,3-triaminoguanidine in step S1 is (2-3):

1.

4. The agent for preventing and treating chicken synoviae mycoplasma disease according to claim 2, characterized in that: The mass ratio of the nanomaterial to doxycycline in step S3 is (1.5-3.5):

1.

5. The agent for preventing and treating chicken synoviae mycoplasma disease according to claim 1, characterized in that: The preparation method of the antioxidant comprises the following steps: (1) Add 5,7-dihydroxyflavone, potassium carbonate and acetone to a reaction kettle, heat and stir under reflux until the solution becomes clear, add a mixed solution of 1,2-dibromoethylbenzene and acetone dropwise, heat and condense under reflux, react for 2-4 hours, filter, add water to the filtrate to precipitate solids, filter, wash, and vacuum dry to obtain an intermediate product; (2) dissolving gallic acid in methanol, adding thionyl chloride dropwise in an ice bath, heating in an oil bath to condense and reflux for 4-6 hours after the addition is complete, and distilling under reduced pressure to obtain methyl gallate; (3) dissolving the methyl gallate obtained in step (2) in N,N-dimethylformamide, adding potassium carbonate, stirring for 5-15 minutes, adding the intermediate product obtained in step (1) and tetrabutylammonium bromide, heating and stirring to react for 4-6 hours, extracting with ethyl acetate, washing the obtained organic layer with saturated sodium chloride, then drying with anhydrous sodium sulfate, and separating by silica gel column chromatography to obtain an antioxidant.

6. The agent for preventing and treating chicken synoviae mycoplasma disease according to claim 5, characterized in that: The molar ratio of 5,7-dihydroxyflavone to 1,2-dibromoethylbenzene in step (1) is 1:(3-5).

7. The agent for preventing and treating chicken synoviae mycoplasma disease according to claim 5, characterized in that: The molar ratio of methyl gallate to the intermediate product in step (3) is (4-5):

1.

8. The agent for preventing and treating chicken synoviae mycoplasma disease according to claim 1, characterized in that: The preservatives are phenoxyethanol and / or parabens.

9. The agent for preventing and treating chicken synoviae mycoplasma disease according to claim 1, characterized in that: The particle size of the silicon dioxide is 800-1200 meshes.

10. A method for preparing the agent for preventing and treating chicken synoviae mycoplasma disease according to any one of claims 1 to 9, characterized in that: The following steps are included: The nanomaterial-modified doxycycline, glucose, sodium chloride, sodium dihydrogen phosphate, antioxidant, preservative and silicon dioxide are mixed and stirred for 1-2 hours, and dried to obtain a medicine.