A veterinary composition for the treatment of respiratory diseases and a method for its preparation

Abstract

The present application relates to the field of veterinary medicine, in particular to a kind of veterinary composition for treating respiratory diseases and preparation method thereof, wherein the veterinary composition for treating respiratory diseases, by weight parts, includes the following raw materials, modified doxycycline hydrochloride 8-10 parts, chlorpheniramine maleate 7-10 parts, nutritional fortifier 17-18 parts, ammonium chloride 60-66 parts, sodium chloride 5-6 parts.The veterinary composition for treating respiratory diseases prepared by the present application has the advantages of good therapeutic effect and small side effect.

Description

Technical Field

[0001] This invention relates to the field of veterinary drugs, and more specifically to a veterinary drug composition for treating respiratory diseases and its preparation method. Background Technology

[0002] With the arrival of winter, respiratory diseases become prevalent in poultry, especially broilers, which are highly susceptible. Sudden climate changes, overcrowding, and stress factors such as vaccination can all trigger the disease. The main symptoms begin with runny nose and sneezing, gradually progressing to coughing and difficulty breathing. Later stages show eyelid swelling, tearing, and the tears changing from clear to thick, even caseous exudate. The eyes bulge out like tumors, eventually leading to blindness. The disease can last for more than a month, with mortality rates exceeding 30% in chicks aged 4-8 weeks. The large-scale deaths of poultry cause significant economic losses for farmers, making medications for treating poultry respiratory diseases a focus of attention in the livestock industry.

[0003] Treatment of respiratory infections in chickens often requires the use of antibiotics, such as amoxicillin, florfenicol, ampicillin, and oxytetracycline. However, antibiotics may leave residues in poultry, disrupt the stability of their gut microbiota, and weaken their immunity. Therefore, developing a veterinary drug that can effectively treat respiratory diseases and is less likely to cause side effects is crucial.

[0004] Patent CN102846652A discloses a veterinary drug for treating viral respiratory diseases in poultry. The veterinary drug, which is formulated by mixing ribavirin, ciprofloxacin lactate, aminophylline, and glucose, has the advantages of significant efficacy and convenient use. However, the high proportion of ribavirin in its formula can easily reduce the egg production of poultry and decrease the fertilization rate of hatching eggs. In addition, ribavirin is explicitly listed as a prohibited drug for food animals.

[0005] Patent CN102846636A discloses a veterinary drug for treating respiratory diseases in poultry. Its ingredients include enrofloxacin hydrochloride, moroxydine hydrochloride, aspirin, vitamin A, vitamin E, vitamin C, and glucose, which can effectively treat respiratory diseases in poultry. However, long-term use of enrofloxacin hydrochloride can irritate the gastrointestinal tract of poultry, and high doses can cause liver damage; long-term use of moroxydine hydrochloride can cause internal bleeding and decreased egg production in poultry; aspirin is highly acidic and easily irritates the gastrointestinal tract, and high doses can induce ulcers and kidney damage.

[0006] Therefore, there is an urgent need in the market for a veterinary drug composition that has good therapeutic effects and few side effects for treating respiratory diseases. Summary of the Invention

[0007] In view of the problems existing in the prior art, the purpose of this invention is to obtain a veterinary drug composition for treating respiratory diseases with good therapeutic effect and few side effects.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] The present invention provides a veterinary drug composition for treating respiratory diseases, comprising, by weight, the following raw materials: 8-10 parts of modified doxycycline hydrochloride, 7-10 parts of chlorpheniramine maleate, 17-18 parts of nutritional fortifier, 60-66 parts of ammonium chloride, and 5-6 parts of sodium chloride.

[0010] This application uses doxycycline hydrochloride and chlorpheniramine maleate, antibiotics that are effective in treating respiratory diseases, as well as nutritional fortifiers, ammonium chloride with expectorant effects, and sodium chloride with bactericidal, anti-inflammatory, and electrolyte-replenishing effects as additives, so that the prepared veterinary drug composition has good therapeutic effects and few side effects.

[0011] In some embodiments, the preparation method of modified doxycycline hydrochloride includes the following steps:

[0012] A1. Add N,N-dimethyldodecylamine, epichlorohydrin and methanol to a reaction vessel, heat to 40-50℃ and react for 1-3 hours, wash and dry to obtain the compound;

[0013] A2. Add gelatin to deionized water, swell at room temperature for 1-2 hours, then heat to 45-55℃ and stir for 0.5-1.5 hours. Add 5-10 wt% sodium hydroxide aqueous solution to adjust the pH to 9-10, add the compound obtained in step A1, react at 45-55℃ for 4-6 hours, wash and dry to obtain modified gelatin.

[0014] A3. Add the modified gelatin obtained in step A2 to deionized water, let it swell at room temperature for 1-2 hours, then heat it to 45-55℃ and stir for 1-2 hours to obtain the binder;

[0015] A4. Add the binder and doxycycline hydrochloride obtained in step A3 to a fluidized bed for granulation, wherein the inlet air temperature is 30-40℃ and the inlet air volume is 40-60 m³ / h. 3 The peristaltic pump operates at a speed of 20-30 rpm and an atomization pressure of 0.04-0.06 MPa. After drying, modified doxycycline hydrochloride is obtained.

[0016] Doxycycline hydrochloride is effective in treating respiratory infections caused by bacteria and mycoplasma. However, when administered, doxycycline hydrochloride can bind with calcium and magnesium ions in the chicken's digestive tract, forming complexes that reduce intestinal calcium absorption. It can also bind with calcium ions in the blood to form insoluble calcium salts that are excreted, leading to calcium deficiency in chickens and causing symptoms such as paralysis and soft-shelled eggs. Furthermore, the efficacy of doxycycline hydrochloride decreases after binding with calcium ions. To address this issue, this application uses gelatin containing a quaternary ammonium salt structure to encapsulate doxycycline hydrochloride. The quaternary ammonium salt can bind with calcium ions in the chicken's body, reducing the binding of calcium ions by the slowly released doxycycline hydrochloride. Moreover, after the veterinary drug composition has acted upon in the gastrointestinal tract, the gelatin shell can be absorbed by the chicken, providing nutritional supplementation.

[0017] In some embodiments, the mass ratio of gelatin to compound in step A2 is 1:(0.2-0.4).

[0018] By selecting specific ratios of gelatin and compounds, this application can ensure that the gelatin chain segments contain a large number of quaternary ammonium salt structures, while ensuring that the hydrophobic segments on the compounds do not affect the hydrophilicity of the gelatin. This can reduce the side effects of veterinary drug compositions while making the gelatin easier to digest and absorb.

[0019] In some embodiments, the mass ratio of the modified gelatin to deionized water in step A3 is 1:(5-7).

[0020] In some embodiments, the mass ratio of doxycycline hydrochloride to binder in step A4 is 1:(3-5).

[0021] This application achieves good gelatin dissolution and ensures the viscosity of the binder by selecting a specific ratio of gelatin and deionized water. By selecting a specific ratio of doxycycline hydrochloride and the binder, doxycycline hydrochloride can be uniformly coated, giving the veterinary drug composition a better sustained-release effect.

[0022] In some embodiments, the veterinary drug composition for treating respiratory diseases further contains 2-4 parts by weight of vitamin B sustained-release microspheres.

[0023] In some embodiments, the preparation method of the vitamin B sustained-release microspheres includes the following steps:

[0024] B1. Add vitamin B and starch to deionized water and stir at room temperature for 20-30 minutes. Then, granulate the mixture in an extruder-spheronizer and sieve it to obtain the drug-loaded pellet core.

[0025] B2. Add ethyl cellulose, oxalic acid and catalyst to a reaction vessel, heat to 240-260℃ and react for 50-60 min, cool to 25-30℃ and add triethylamine and react for 50-70 min to obtain modified ethyl cellulose. Add the obtained modified ethyl cellulose to ethanol and stir at 50-60℃ for 30-40 min to obtain a coating solution.

[0026] B3. Place the drug-loaded pellet core obtained in step B1 in a fluidized bed, then coat it with the coating solution obtained in step B2, and dry it to obtain vitamin B sustained-release microcapsules.

[0027] Chlorpheniramine maleate is effective in treating symptoms such as runny nose and sneezing. However, its use may cause symptoms in poultry such as lethargy and thirst, leading to decreased feed intake and weight loss. This application incorporates vitamin B, which has anti-respiratory infection, digestive-promoting, and nervous system-improving effects, into the veterinary drug composition system, which can reduce the side effects of chlorpheniramine maleate in poultry. However, high doses of vitamin B can stimulate gastric acid secretion, causing stomach discomfort in poultry. To address these issues, this application prepares drug-loaded pellets by blending vitamin B with starch and using modified ethyl cellulose as the coating solution to prepare sustained-release vitamin B microspheres. This not only allows for slow release of vitamin B but also timely release to alleviate the side effects of chlorpheniramine maleate. A possible reason is that the modified ethyl cellulose contains a salt formed by the reaction of carboxyl groups and triethylamine, which can cause ruptures and micropores on the surface of the coating in the intestine, increasing the sustained-release rate of vitamin B and allowing it to exert its anti-respiratory infection and nervous system-improving effects promptly.

[0028] In some embodiments, the mass ratio of vitamin B to starch is (2.5-3.5):1.

[0029] In some embodiments, the mass ratio of ethyl cellulose, oxalic acid and triethylamine in step B2 is 1:(0.2-0.3):(0.2-0.3).

[0030] The content of oxalic acid and triethylamine affects the content of carboxyl groups on vitamin B sustained-release microspheres. This application, by limiting the mass ratio of ethyl cellulose and oxalic acid, enables vitamin B sustained-release microspheres to have a better sustained-release effect while releasing vitamin B in a timely manner, which is beneficial to improving the therapeutic effect of veterinary drug compositions and reducing their side effects.

[0031] In some embodiments, the mass ratio of the modified ethyl cellulose to ethanol is (0.17-0.2):1.

[0032] In some embodiments, the mass ratio of the drug-loaded pellet core to the coating solution in step B3 is (0.3-0.4):1.

[0033] Preferably, the fluidized bed has an airflow rate of 20-30 Hz, an airflow temperature of 25-35°C, and an atomization pressure of 0.9-1.1 bar.

[0034] In some embodiments, the nutrient fortifier is a mixture of taurine and citric acid in a mass ratio of (1.1-1.3):1.

[0035] Taurine improves protein utilization; adding taurine to laying hen diets can enhance production performance, regulate lipid metabolism, improve antioxidant status, and improve egg quality. Citric acid can regulate the acid-base balance in poultry and maintain intestinal health. The combined use of these two ingredients can enhance antioxidant effects, activate cells, and improve poultry immunity. Furthermore, citric acid and taurine can act as antioxidants in veterinary drug compositions, reducing oxygen damage to gelatin and extending the shelf life of the veterinary drug composition.

[0036] Another aspect of the present invention provides a method for preparing a veterinary drug composition for treating respiratory diseases, comprising the following steps: mixing modified doxycycline hydrochloride, chlorpheniramine maleate, a nutritional fortifier, ammonium chloride, and sodium chloride at 25-30°C for 30-60 minutes to obtain the composition.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] (1) The present invention uses doxycycline hydrochloride and chlorpheniramine maleate, which are antibiotics that are relatively effective in treating respiratory diseases, as well as nutritional fortifiers, ammonium chloride with expectorant effect and sodium chloride with bactericidal, anti-inflammatory and electrolyte-supplementing effects, as additives to make the prepared veterinary drug composition have good therapeutic effect and few side effects.

[0039] (2) The present invention uses gelatin containing quaternary ammonium salt structure to encapsulate doxycycline hydrochloride. Quaternary ammonium salt can complex calcium ions in chickens, reducing the complexation of calcium ions by the slowly released doxycycline hydrochloride. After the veterinary drug composition takes effect through the gastrointestinal tract, the gelatin shell can be absorbed by the chicken to supplement nutrition.

[0040] (3) In this invention, vitamin B is mixed with starch to prepare drug-loaded pellet cores. Ethyl cellulose containing some carboxylate groups is used as coating liquid to prepare vitamin B sustained-release microspheres, which not only have sustained-release function, but also enable vitamin B to be released in time to alleviate the side effects of chlorpheniramine maleate. Detailed Implementation

[0041] The present invention will be described below with reference to specific embodiments. It should be noted that the following embodiments are examples of the present invention and are used only to illustrate the invention, not to limit it. Other combinations and various modifications within the scope of the present invention can be made without departing from its spirit or scope.

[0042] In the following examples and comparative examples, except for modified doxycycline hydrochloride and modified chlorpheniramine maleate, all other compounds and related reagents used were commercially available. Among them, the gelatin was grade 180 and was purchased from Xi'an Jinxiang Pharmaceutical Excipients Co., Ltd.; the vitamin B was compound vitamin B and was purchased from Shandong Aicai Biotechnology Co., Ltd.; and the ethyl cellulose was pharmaceutical grade N50 and was purchased from Xi'an Jinxiang Pharmaceutical Excipients Co., Ltd.

[0043] Preparation Example 1

[0044] The preparation method of modified doxycycline hydrochloride-1 includes the following steps:

[0045] A1. Add 9g of N,N-dimethyldodecylamine, 5g of epichlorohydrin and 5ml of anhydrous methanol to a reaction vessel, heat to 45℃ and react for 2h, wash and dry to obtain the compound;

[0046] A2. Add 10g of gelatin to 30g of deionized water, let it swell at room temperature for 1.5h, then heat to 50℃ and stir for 1h. Add 7wt% sodium hydroxide aqueous solution to adjust the pH to 10, add 3g of the compound obtained in step A1, react at 50℃ for 5h, wash and dry to obtain modified gelatin.

[0047] A3. Add 10g of modified gelatin obtained in step A2 to 60g of deionized water, let it swell at room temperature for 1.5h, then heat it to 50℃ and stir for 1.5h to obtain the binder;

[0048] A4. Add 40g of binder and 10g of doxycycline hydrochloride obtained in step A3 to a fluidized bed for granulation, wherein the inlet air temperature is 35℃ and the inlet air volume is 50m³ / h. 3 / h, the peristaltic pump speed is 25rpm, the atomization pressure is 0.05MPa, and after drying, modified doxycycline hydrochloride-1 is obtained.

[0049] Preparation Example 2

[0050] The preparation method of modified doxycycline hydrochloride-2 is the same as that in preparation example 1, except that the amount of compound A added in step A2 is 5g.

[0051] Preparation Example 3

[0052] The preparation method of modified doxycycline hydrochloride-3 is the same as that in preparation example 1, except that the amount of deionized water added in step A3 is 80g.

[0053] Preparation Example 4

[0054] The preparation method of modified doxycycline hydrochloride-4 is the same as that in preparation example 1, except that the amount of binder added in step A4 is 20g.

[0055] Preparation Example 5

[0056] The preparation method of vitamin B sustained-release microcapsules-1 includes the following steps:

[0057] B1. Add 30g of vitamin B and 10g of corn starch to 8g of deionized water and stir at room temperature for 25 minutes. Then, granulate the mixture in an extruder-spheronizer and pass it through an 80-mesh sieve to obtain the drug-loaded pellet core.

[0058] B2. Add 10g of ethyl cellulose, 2.5g of oxalic acid and 0.5g of 80wt% sulfuric acid to a reaction vessel, heat to 250℃ and react for 55min, cool to 27℃ and add 2.5g of triethylamine and react for 60min to obtain modified ethyl cellulose. Add 1.85g of the obtained modified ethyl cellulose to 10g of anhydrous ethanol and stir at 55℃ for 35min to obtain a coating solution.

[0059] B3. Place the 3.5g drug-loaded pellet core obtained in step B1 into a fluidized bed with an air inlet flow rate of 25Hz, an air inlet temperature of 30℃, and an atomization pressure of 1bar. Then, coat the pellet with 10g of the coating solution obtained in step B2, spray the solution at a rate of 2g / min, and dry to obtain vitamin B sustained-release microparticles-1.

[0060] Preparation Example 6

[0061] The preparation method of vitamin B sustained-release microcapsules-2 is the same as that in preparation example 5, except that the amount of oxalic acid added in step B2 is 3.5g.

[0062] Preparation Example 7

[0063] The preparation method of vitamin B sustained-release microcapsules-3 is the same as that in preparation example 5, except that the amount of triethylamine added in step B2 is 3.5g.

[0064] Example 1

[0065] A veterinary drug composition for treating respiratory diseases, comprising, by weight, the following raw materials: 9 parts modified doxycycline hydrochloride-1, 8 parts chlorpheniramine maleate, 18 parts nutritional fortifier, 63 parts ammonium chloride, and 6 parts sodium chloride.

[0066] The nutritional fortifier is a mixture of taurine and citric acid in a mass ratio of 1.2:1.

[0067] The preparation method of the veterinary drug composition for treating respiratory diseases in this embodiment includes the following steps: mixing modified doxycycline hydrochloride-1, chlorpheniramine maleate, nutritional fortifier, ammonium chloride, and sodium chloride at 27°C using a mixer for 45 minutes to obtain the final product.

[0068] Example 2

[0069] A veterinary drug composition for treating respiratory diseases, comprising, by weight, the following raw materials: 8 parts modified doxycycline hydrochloride, 7 parts chlorpheniramine maleate, 17 parts nutritional fortifier, 60 parts ammonium chloride, and 5 parts sodium chloride.

[0070] The nutritional fortifier is a mixture of taurine and citric acid in a mass ratio of 1.1:1.

[0071] The preparation method of the veterinary drug composition for treating respiratory diseases in this embodiment includes the following steps: mixing modified doxycycline hydrochloride-1, chlorpheniramine maleate, nutritional fortifier, ammonium chloride, and sodium chloride at 25°C using a stirrer for 60 minutes to obtain the final product.

[0072] Example 3

[0073] A veterinary drug composition for treating respiratory diseases, comprising, by weight, the following raw materials: 10 parts modified doxycycline hydrochloride-1, 10 parts chlorpheniramine maleate, 18 parts nutritional fortifier, 66 parts ammonium chloride, and 6 parts sodium chloride.

[0074] The nutritional fortifier is a mixture of taurine and citric acid in a mass ratio of 1.3:1.

[0075] The preparation method of the veterinary drug composition for treating respiratory diseases in this embodiment includes the following steps: mixing modified doxycycline hydrochloride-1, chlorpheniramine maleate, nutritional fortifier, ammonium chloride, and sodium chloride at 30°C using a stirrer for 30 minutes to obtain the final product.

[0076] Example 4

[0077] A veterinary drug composition for treating respiratory diseases and its preparation method are disclosed. The specific implementation method is the same as that in Example 1, except that modified doxycycline hydrochloride-1 is replaced with modified doxycycline hydrochloride-2 in an equal amount.

[0078] Example 5

[0079] A veterinary drug composition for treating respiratory diseases and its preparation method are disclosed. The specific implementation method is the same as that in Example 1, except that the modified doxycycline hydrochloride-1 is replaced with an equal amount of modified doxycycline hydrochloride-3.

[0080] Example 6

[0081] A veterinary drug composition for treating respiratory diseases and its preparation method are disclosed. The specific implementation method is the same as that in Example 1, except that the modified doxycycline hydrochloride-1 is replaced with an equal amount of modified doxycycline hydrochloride-4.

[0082] Example 7

[0083] A veterinary drug composition for treating respiratory diseases, comprising, by weight, the following raw materials: 9 parts modified doxycycline hydrochloride-1, 8 parts chlorpheniramine maleate, 18 parts nutritional fortifier, 63 parts ammonium chloride, 6 parts sodium chloride, and 3 parts vitamin B sustained-release microcapsules-1.

[0084] The nutritional fortifier is a mixture of taurine and citric acid in a mass ratio of 1.2:1.

[0085] The preparation method of the veterinary drug composition for treating respiratory diseases in this embodiment includes the following steps: mixing modified doxycycline hydrochloride-1, chlorpheniramine maleate, vitamin B sustained-release microcapsules-1, nutritional fortifier, ammonium chloride, and sodium chloride at 27°C for 45 minutes using a mixer to obtain the final product.

[0086] Example 8

[0087] A veterinary drug composition for treating respiratory diseases and its preparation method are described. The specific implementation method is the same as in Example 7, except that vitamin B sustained-release microcapsules-1 are replaced with vitamin B sustained-release microcapsules-2 in equal amounts.

[0088] Example 9

[0089] A veterinary drug composition for treating respiratory diseases and its preparation method are described. The specific implementation method is the same as in Example 7, except that vitamin B sustained-release microcapsules-1 are replaced with vitamin B sustained-release microcapsules-3 in equal amounts.

[0090] Example 10

[0091] A veterinary drug composition for treating respiratory diseases and its preparation method are described. The specific implementation method is the same as in Example 7, except that vitamin B sustained-release microcapsules-1 are replaced with an equal amount of vitamin B.

[0092] Comparative Example 1

[0093] A veterinary drug composition for treating respiratory diseases and its preparation method are disclosed. The specific implementation method is the same as in Example 1, except that the modified doxycycline hydrochloride-1 is replaced with an equal amount of doxycycline hydrochloride.

[0094] Performance testing

[0095] The performance of the veterinary drug compositions for treating respiratory diseases obtained in the above embodiments and comparative examples was tested:

[0096] The experimental feeding area, chicken cages, and feed troughs were thoroughly disinfected. The newly hatched chicks were transferred to the feeding area and raised to 13 days old. Chicks of roughly equal weight were selected and their feces were examined under a microscope. Chicks without fungal diseases were randomly grouped and their pre-experiment weights were recorded.

[0097] This experiment was divided into 12 groups: 11 drug groups and 1 infection control group (infected, no drug administration), with 50 chickens in each group. Chicks were infected with infectious Mycoplasma gallisepticum. After infection, the mental state, feed intake, water intake, and fecal condition of the chicks in each group were observed daily. Starting from the 5th day after infection, except for the infection control group, all other groups were simultaneously administered the drug at a 1:100 mass ratio mixed with their feed, with free access to food. Medication was administered continuously for 4 days. On the last day of treatment, i.e., the 8th day after challenge, the mortality rate, cure rate, and symptomatic rate at the end of the treatment were calculated using the following formula.

[0098] Mortality rate = (Number of dead animals / Number of experimental animals) × 100%;

[0099] Cure rate = (Number of cured animals / Number of experimental animals) × 100%;

[0100] The symptomatic rate at the end of the test = (number of animals with symptoms at the end of the test) / (number of test animals) × 100%.

[0101] The test results are shown in Table 1:

[0102] Table 1

[0103] Example 1 4 88 8 Example 2 4 86 10 Example 3 6 88 6 Example 4 6 84 10 Example 5 8 84 8 Example 6 6 84 10 Example 7 4 90 6 Example 8 4 88 8 Example 9 4 86 10 Example 10 6 88 6 Comparative Example 1 10 78 12 Infection control 16 62 24

[0104] As shown in Table 1, the veterinary drug compositions for treating respiratory diseases in Examples 1-3 of this invention have good therapeutic effects. A comparison between Example 4 and Example 1 shows that changing the ratio of gelatin to compound A makes the gelatin less easily digested and absorbed, leading to a decrease in the therapeutic effect of the veterinary drug composition. A comparison between Examples 5 and 6 and Example 1 shows that changing the ratio of gelatin to deionized water or the ratio of doxycycline hydrochloride to the binder prevents the doxycycline hydrochloride from being uniformly coated, resulting in a decrease in the therapeutic effect of the veterinary drug composition. A comparison between Example 7 and Example 1 shows that… The therapeutic effect of the veterinary drug composition was further improved after the addition of vitamin B sustained-release microcapsules. The comparison between Examples 8, 9 and Example 7 shows that changing the ratio of oxalic acid or triethylamine and ethyl cellulose will result in a higher content of carboxyl groups on the vitamin B sustained-release microcapsules, which will reduce the coating rate of the drug-loaded core and thus reduce the therapeutic effect of the veterinary drug composition. The comparison between Example 10 and Example 7 shows that the direct addition of vitamin B will reduce the therapeutic effect of the veterinary drug composition. The comparison between Comparative Example 1 and Example 1 shows that the therapeutic effect of the veterinary drug composition is poor when only doxycycline hydrochloride is added.

[0105] The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it. They should not be used to limit the scope of protection of the present invention. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A veterinary drug composition for treating respiratory diseases, characterized in that, By weight, it includes the following raw materials: 8-10 parts modified doxycycline hydrochloride, 7-10 parts chlorpheniramine maleate, 17-19 parts nutrient fortifier, 60-66 parts ammonium chloride, and 5-7 parts sodium chloride.

2. The veterinary drug composition for treating respiratory diseases according to claim 1, characterized in that, The method for preparing the modified doxycycline hydrochloride includes the following steps: A1. Add N,N-dimethyldodecylamine, epichlorohydrin and methanol to a reaction vessel, heat to 40-50℃ and react for 1-3 hours, wash and dry to obtain the compound; A2. Add gelatin to deionized water, swell at room temperature for 1-2 hours, then heat to 45-55℃ and stir for 0.5-1.5 hours. Add 5-10 wt% sodium hydroxide aqueous solution to adjust the pH to 9-10, add the compound obtained in step A1, react at 45-55℃ for 4-6 hours, wash and dry to obtain modified gelatin. A3. Add the modified gelatin obtained in step A2 to deionized water, let it swell at room temperature for 1-2 hours, then heat it to 45-55℃ and stir for 1-2 hours to obtain the binder; A4. Add the binder obtained in step A3 and the modified doxycycline hydrochloride obtained in step A2 to a fluidized bed for granulation, wherein the inlet air temperature is 30-40℃ and the inlet air volume is 40-60 m³ / h. 3 The peristaltic pump operates at a speed of 20-30 rpm and an atomization pressure of 0.04-0.06 MPa. After drying, modified doxycycline hydrochloride is obtained.

3. The veterinary drug composition for treating respiratory diseases according to claim 2, characterized in that, The mass ratio of gelatin to compound in step A2 is 1:(0.2-0.4).

4. The veterinary drug composition for treating respiratory diseases according to claim 2, characterized in that, The mass ratio of modified gelatin to deionized water in step A3 is 1:(5-7).

5. The veterinary drug composition for treating respiratory diseases according to claim 2, characterized in that, The mass ratio of modified doxycycline hydrochloride to binder in step A4 is 1:(3-5).

6. The veterinary drug composition for treating respiratory diseases according to claim 1, characterized in that, The veterinary drug composition for treating respiratory diseases also contains 2-4 parts by weight of vitamin B sustained-release microcapsules.

7. The veterinary drug composition for treating respiratory diseases according to claim 6, characterized in that, The preparation method of the vitamin B sustained-release microcapsules includes the following steps: B1. Add vitamin B and starch to deionized water and stir at room temperature for 20-30 minutes. Then, granulate the mixture in an extruder-spheronizer and sieve it to obtain the drug-loaded pellet core. B2. Add ethyl cellulose, oxalic acid and catalyst to a reaction vessel, heat to 240-260℃ and react for 50-60 min, cool to 25-30℃ and add triethylamine and react for 50-70 min to obtain modified ethyl cellulose. Add the obtained modified ethyl cellulose to ethanol and stir at 50-60℃ for 30-40 min to obtain a coating solution. B3. Place the drug-loaded pellet core obtained in step B1 in a fluidized bed, then coat it with the coating solution obtained in step B2, and dry it to obtain vitamin B sustained-release microcapsules.

8. The veterinary drug composition for treating respiratory diseases according to claim 7, characterized in that, The mass ratio of ethyl cellulose to oxalic acid in step B2 is 1:(0.2-0.3):(0.2-0.3).

9. The veterinary drug composition for treating respiratory diseases according to claim 1, characterized in that, The nutrient fortifier is a mixture of taurine and citric acid in a mass ratio of (1.1-1.3):

1.

10. A method for preparing a veterinary drug composition for treating respiratory diseases according to any one of claims 1-5, characterized in that, The process includes the following steps: mixing modified doxycycline hydrochloride, chlorpheniramine maleate, nutrient fortifier, ammonium chloride, and sodium chloride at 25-30℃ for 30-60 minutes to obtain the final product.