Veterinary anti-bronchial blockage sustained-release medicine and preparation method thereof

Abstract

The invention belongs to the technical field of veterinary drug preparation, and particularly relates to an anti-bronchial blockage sustained-release drug for veterinary use and a preparation method thereof, and the anti-bronchial blockage sustained-release drug comprises the following components in parts by mass: 30-34 parts of cysteine-ciprofloxacin hydrochloride emulsion gel, 3-6 parts of roxithromycin loaded modified silicon dioxide, 10-12 parts of sodium sulfate and 20-25 parts of sodium chloride. The prepared sustained-release medicine can reduce the administration frequency, is durable in disease resistance, can resist gastric acid decomposition of livestock, and improves the absorption efficiency of intestinal tracts to the medicine.

Description

Technical Field

[0001] The present invention belongs to the technical field of veterinary drug preparation, and particularly relates to a slow-release veterinary drug for treating bronchial obstruction and a preparation method thereof. Technical Background

[0002] With the development of China's animal husbandry, sudden diseases among poultry are becoming more and more frequent. Some minor diseases can recover on their own without medication, but some diseases can endanger the lives of poultry. Among them, bronchial obstruction is a common respiratory disease in animals, especially prevalent in poultry farming. This disease can cause dyspnea and slow growth in poultry such as chickens, and can even lead to a large number of deaths in severe cases, causing significant economic losses to the breeding industry. This disease is usually caused by various factors, including environmental factors and pathogen infections. Bronchial obstruction is a serious respiratory disease that mainly affects poultry, especially broiler chickens and laying hens. The common symptoms of bronchial obstruction are open-mouth breathing and wheezing, with a relatively high mortality rate and great difficulty in treatment. At present, there are many types of drugs for treating bronchial obstruction on the market, but most drugs can only relieve symptoms, and the effects are often not lasting. Therefore, researching and developing new drugs for treating bronchial obstruction is of great significance for improving the treatment effect and ensuring the healthy development of the breeding industry.

[0003] For example, CN106177283A discloses a "yao medicine composition for treating chronic bronchitis and bronchial asthma", which is prepared from the main traditional Chinese medicine components of gourd drill, kudzu root, eucommia leaves, gnetum montanum, schizandra sphenanthera, polygonum cuspidatum, patrinia scabiosaefolia, eucalyptus leaves, speranskia tuberculata, paederia scandens and salvia miltiorrhiza, and has a good therapeutic effect on bronchitis and bronchial asthma. Another example is that CN106729619A discloses a "compound preparation for treating chicken bronchial obstruction and its preparation method", which is prepared from components such as cortex mori, anemarrhena asphodeloides, peucedanum praeruptorum, honeysuckle, forsythia, scutellaria baicalensis, coptis chinensis, portulaca oleracea, liquorice, shikimic acid, antibacterial peptide, vitamin C and allicin, and has a good therapeutic effect on chicken bronchial obstruction. Still another example is that CN106668177A discloses a "traditional Chinese medicine combination for chicken infectious bronchitis and its preparation method", which is prepared from the main components of honeysuckle, scutellaria baicalensis and forsythia, and has a good therapeutic effect on chicken infectious bronchitis and respiratory diseases caused by exogenous wind-heat.

[0004] However, the above patents mainly focus on traditional Chinese medicine, and it is well-known that traditional Chinese medicine takes a relatively long time to take effect and cannot effectively and promptly cure some acute diseases. Therefore, some researchers have developed drugs mainly based on Western medicine. For example, CN110960550A discloses "a composition for preventing and treating poultry bronchial obstruction and its preparation method", including ammonium chloride, alum, taurine, citric acid, and doxycycline hydrochloride, which has obvious effects of relieving asthma, rescuing the lungs, and strong drug potency. Another example is that CN106619686A discloses "a Western medicine for treating bronchiectasis", which is made mainly of β,β-dimethylacryloylshikonin, ethoxychelerythrine, eupatorium lactone A, emetine hydrochloride, raddeanin A, raddeanin A, dalbergin, 7,8-dihydroxy-4-phenylcoumarin, and sinpeimine-3β-D-glucoside, and has the characteristics of fast onset, stable effect, convenient carrying and taking, and no toxic side effects after long-term use. Another example is that CN106511363A discloses "a Western medicine combination for treating bronchitis and its preparation method", which is prepared mainly from excipients, amino acids, total flavonoids, mannitol, chlorpheniramine, metronidazole, aminophylline, anthocyanins, morroniside, chlorpheniramine maleate, oryzanol, budesonide, amino acids, and ethanol solution, and can cure chronic bronchitis fundamentally, with a treatment effect far better than existing products and no toxic side effects.

[0005] However, long-term administration of Western medicine to livestock will have a certain impact on the liver and kidneys, and the above-mentioned disclosed patents do not mention and solve this problem.

[0006] Therefore, it is urgent to develop a sustained-release drug that can reduce the dosing frequency and has a long-lasting disease resistance. Summary of the Invention

[0007] In view of the problems existing in the prior art, the present invention provides a veterinary anti-bronchial obstruction sustained-release drug and its preparation method. The sustained-release drug can reduce the dosing frequency and has a long-lasting disease resistance, and at the same time can resist the decomposition of livestock gastric acid and improve the intestinal absorption efficiency of the drug.

[0008] In order to achieve the above object, the technical solutions adopted by the present invention are as follows:

[0009] On the one hand, the present invention provides a veterinary anti-bronchial obstruction sustained-release drug, which includes the following components in parts by mass: 30-34 parts of cysteine-ciprofloxacin hydrochloride emulsion gel, 3-6 parts of roxithromycin-loaded modified silica, 10-12 parts of sodium sulfate, and 20-25 parts of sodium chloride.

[0010] The sustained-release drug of the present application can reduce the dosing frequency and has a long-lasting disease resistance, and at the same time can resist the decomposition of livestock gastric acid and improve the intestinal absorption efficiency of the drug.

[0011] In some embodiments, the sustained-release drug further includes 60-70 parts of glucose.

[0012] By adding glucose, this application can mask the taste of the drug, making it easier to administer to livestock, preventing the phenomenon of unpalatability and thus reducing the waste of drug efficacy.

[0013] In some embodiments, the preparation method of the cysteine-ciprofloxacin hydrochloride emulsion gel comprises the following steps:

[0014] A1. Dissolve alginic acid in a 1-2 wt% acetic acid solution to prepare a 3-4 wt% alginic acid solution;

[0015] A2. Mix acetylcysteine, ciprofloxacin hydrochloride, and ZnCl2 with water to prepare a mixed aqueous solution;

[0016] A3. Add the mixed aqueous solution in step A2 to the alginic acid solution in step A1, and finally add glycyrrhizic acid and stir evenly to obtain an emulsion gel.

[0017] In the past, when taking Western medicine directly, it would be directly absorbed by the intestine and needed to be administered frequently in a short period to effectively treat the disease, which greatly increased the drug toxicity and the duration of drug efficacy was short. In this application, by making acetylcysteine and ciprofloxacin hydrochloride into an emulsion gel, the two effective drugs can have a sustained-release ability, improve the duration of drug efficacy, reduce the administration frequency and reduce the drug toxicity.

[0018] In some embodiments, in the mixed aqueous solution, the mass ratio of acetylcysteine, ciprofloxacin hydrochloride, ZnCl2 and water is 1:(0.9-1.1):(4-6):(50-60).

[0019] Preferably, in the mixed aqueous solution, the mass ratio of acetylcysteine, ciprofloxacin hydrochloride, ZnCl2 and water is 1:1:5:55.

[0020] By regulating the mass ratio of acetylcysteine, ciprofloxacin hydrochloride, ZnCl2 and water in this application, acetylcysteine and ciprofloxacin hydrochloride can be linked together with alginic acid through chelating zinc ions, preventing the reduction of the ZnCl2 mass concentration from causing part of acetylcysteine and ciprofloxacin hydrochloride to be unable to connect with alginic acid and thus reducing the drug content.

[0021] In some embodiments, the mass ratio of the alginic acid in step A1 to the acetylcysteine in step A2 is (3-4):1.

[0022] Preferably, the mass ratio of the alginic acid in step A1 to the acetylcysteine in step A2 is 3.5:1.

[0023] In some embodiments, in step A3, the mass ratio of glycyrrhizic acid to alginic acid is 1:(1-1.2).

[0024] Preferably, in step A3, the mass ratio of glycyrrhizic acid to alginic acid is 1:1.1.

[0025] In the present application, alginic acid can form a gel network. By compounding glycyrrhizic acid with alginic acid, the two are cross-linked by hydrogen bonds to further strengthen the emulsion gel network structure. By regulating the mass ratio of the two, it is possible to prevent the network from being too dense, resulting in a slow release rate and an unclear initial drug effect, thus aggravating the condition.

[0026] In some embodiments, the preparation method of the roxithromycin-loaded modified silica includes the following steps:

[0027] S1. Mix silica and roxithromycin in ethanol, and concentrate and dry under reduced pressure to obtain a roxithromycin-loaded silica precursor;

[0028] S2. Mix the roxithromycin-loaded silica precursor in step S1 with a saturated aqueous solution of β-cyclodextrin and stir, then filter and dry to obtain roxithromycin-loaded modified silica.

[0029] Roxithromycin is an antibacterial and anti-inflammatory drug that can effectively inhibit bronchial obstruction. However, roxithromycin will degrade in gastric acid, which is not conducive to the intestinal absorption of roxithromycin. In the present application, roxithromycin is first loaded onto silica, and then β-cyclodextrin is used as a pore-blocking agent to be mixed with the roxithromycin-loaded silica precursor to block the pores of silica. When the roxithromycin-loaded modified silica enters the stomach, due to the pore-blocking effect of β-cyclodextrin, gastric acid cannot enter the pores of silica, and the roxithromycin therein is retained. The self-made modified silica-loaded roxithromycin can avoid the decomposition of roxithromycin by gastric acid and reach the intestine smoothly to slowly release roxithromycin for intestinal absorption.

[0030] In some embodiments, the mass ratio of silica to roxithromycin is (1-3):1.

[0031] Preferably, the mass ratio of silica to roxithromycin is 2:1.

[0032] In some embodiments, in step S2, the mass ratio of the roxithromycin-loaded silica precursor to β-cyclodextrin is 1:(0.1-0.3).

[0033] In the present application, by regulating the mass ratio of the roxithromycin-loaded silica precursor to β-cyclodextrin, it is possible to prevent the slow release effect from deteriorating due to excessive β-cyclodextrin in the pores of the roxithromycin-loaded silica precursor, resulting in an unclear initial drug effect and thus aggravating the condition.

[0034] On the other hand, the present invention provides a preparation method of a veterinary anti-bronchial obstruction sustained-release drug, which comprises the following steps: mixing cysteine-ciprofloxacin hydrochloride emulsion gel, roxithromycin-loaded silica, sodium sulfate, sodium chloride and glucose evenly, drying and then sealing and bagging to obtain the veterinary anti-bronchial obstruction sustained-release drug.

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

[0036] (1) The present invention uses cysteine-ciprofloxacin hydrochloride emulsion gel, roxithromycin-loaded modified silica, sodium sulfate, glucose and sodium chloride as main raw materials to prepare a veterinary anti-bronchial obstruction sustained-release drug. This drug can reduce the dosing frequency and has a long-lasting disease resistance. At the same time, it can resist the decomposition of livestock gastric acid and improve the intestinal absorption efficiency of the drug.

[0037] (2) The cysteine-ciprofloxacin hydrochloride emulsion gel of the present invention can endow cysteine and ciprofloxacin hydrochloride with sustained-release ability, improve the duration of drug efficacy, reduce the drug toxicity by reducing the dosing frequency.

[0038] (3) The roxithromycin-loaded modified silica of the present invention can avoid the decomposition of roxithromycin by gastric acid, reach the intestine smoothly and release roxithromycin for intestinal absorption. Specific embodiments

[0039] The following will illustrate the present invention in combination with specific implementation schemes. It should be noted that the following examples are examples of the present invention, only for illustrating the present invention, and not for limiting the present invention. Without departing from the main idea or scope of the present invention, other combinations and various improvements within the concept of the present invention can be made.

[0040] In the following preparation examples, alginic acid CAS: 9005-32-7; silica was purchased from Chongqing Tianrun Bioproducts Co., Ltd.

[0041] Preparation Example 1

[0042] The preparation method of cysteine-ciprofloxacin hydrochloride emulsion gel comprises the following steps:

[0043] A1. Dissolve 50 g of alginic acid in a 2 wt% acetic acid solution to prepare a 4 wt% alginic acid solution;

[0044] A2. Mix 14.3 g of acetylcysteine, 14.3 g of ciprofloxacin hydrochloride and 71.5 g of ZnCl2 with 786 mL of water to prepare a mixed aqueous solution;

[0045] A3. Add the mixed aqueous solution in step A2 to the alginic acid solution in step A1, and finally add 45.5 g of glycyrrhizic acid and stir evenly to obtain an emulsion gel.

[0046] Preparation Example 2

[0047] The preparation method of cysteine-ciprofloxacin hydrochloride emulsion gel is the same as that of Preparation Example 1, except that the addition amount of ZnCl2 is 53 g.

[0048] Preparation Example 3

[0049] The preparation method of cysteine-ciprofloxacin hydrochloride emulsion gel is the same as that of Preparation Example 1, except that the addition amount of glycyrrhizic acid is 53 g.

[0050] Preparation Example 4

[0051] The preparation method of roxithromycin-loaded modified silica includes the following steps:

[0052] S1. Mix 20 g of silica and 10 g of roxithromycin in 200 mL of ethanol, and concentrate and dry under reduced pressure to obtain a roxithromycin-loaded silica precursor;

[0053] S2. Mix 30 g of the roxithromycin-loaded silica precursor in step S1 with a saturated aqueous solution containing 6 g of β-cyclodextrin, stir, filter and dry to obtain roxithromycin-loaded modified silica.

[0054] Preparation Example 5

[0055] The preparation method of roxithromycin-loaded modified silica is the same as that of Preparation Example 4, except that the addition amount of β-cyclodextrin is 15 g.

[0056] Preparation Example 6

[0057] The preparation method of roxithromycin-loaded modified silica is the same as that of Preparation Example 4, except that the addition amount of β-cyclodextrin is 1.5 g.

[0058] Example 1

[0059] A veterinary anti-bronchial obstruction sustained-release drug, comprising the following components in parts by mass: 32 parts of cysteine-ciprofloxacin hydrochloride emulsion gel, 5 parts of roxithromycin-loaded modified silica, 11 parts of sodium sulfate and 23 parts of sodium chloride.

[0060] Among them, the cysteine-ciprofloxacin hydrochloride emulsion gel is prepared from Preparation Example 1, and the roxithromycin-loaded modified silica is prepared from Preparation Example 4.

[0061] Preparation method of veterinary anti-bronchial obstruction sustained-release drug, comprising the following steps: mixing cysteine-ciprofloxacin hydrochloride emulsion gel, roxithromycin-loaded silica, sodium sulfate, and sodium chloride evenly by stirring, drying, and then sealing and bagging to obtain the veterinary anti-bronchial obstruction sustained-release drug.

[0062] Example 2

[0063] A veterinary anti-bronchial obstruction sustained-release drug, comprising the following components in parts by mass: 30 parts of cysteine-ciprofloxacin hydrochloride emulsion gel, 3 parts of roxithromycin-loaded modified silica, 10 parts of sodium sulfate, and 20 parts of sodium chloride.

[0064] Among them, the cysteine-ciprofloxacin hydrochloride emulsion gel is prepared from Preparation Example 1, and the roxithromycin-loaded modified silica is prepared from Preparation Example 4.

[0065] Preparation method of veterinary anti-bronchial obstruction sustained-release drug, comprising the following steps: mixing cysteine-ciprofloxacin hydrochloride emulsion gel, roxithromycin-loaded silica, sodium sulfate, and sodium chloride evenly by stirring, drying, and then sealing and bagging to obtain the veterinary anti-bronchial obstruction sustained-release drug.

[0066] Example 3

[0067] A veterinary anti-bronchial obstruction sustained-release drug, comprising the following components in parts by mass: 34 parts of cysteine-ciprofloxacin hydrochloride emulsion gel, 6 parts of roxithromycin-loaded modified silica, 12 parts of sodium sulfate, and 25 parts of sodium chloride.

[0068] Among them, the cysteine-ciprofloxacin hydrochloride emulsion gel is prepared from Preparation Example 1, and the roxithromycin-loaded modified silica is prepared from Preparation Example 4.

[0069] Preparation method of veterinary anti-bronchial obstruction sustained-release drug, comprising the following steps: mixing cysteine-ciprofloxacin hydrochloride emulsion gel, roxithromycin-loaded silica, sodium sulfate, and sodium chloride evenly by stirring, drying, and then sealing and bagging to obtain the veterinary anti-bronchial obstruction sustained-release drug.

[0070] Example 4

[0071] A veterinary anti-bronchial obstruction sustained-release drug, comprising the following components in parts by mass: 32 parts of cysteine-ciprofloxacin hydrochloride emulsion gel, 5 parts of roxithromycin-loaded modified silica, 11 parts of sodium sulfate, 23 parts of sodium chloride, and 65 parts of glucose.

[0072] Among them, the cysteine-ciprofloxacin hydrochloride emulsion gel is prepared from Preparation Example 1, and the roxithromycin-loaded modified silica is prepared from Preparation Example 4.

[0073] Preparation method of veterinary anti-bronchial obstruction sustained-release drug, comprising the following steps: mixing cysteine-ciprofloxacin hydrochloride emulsion gel, roxithromycin-loaded silica, sodium sulfate, sodium chloride and glucose evenly, drying and then sealing and bagging to obtain the veterinary anti-bronchial obstruction sustained-release drug.

[0074] Example 5

[0075] A veterinary anti-bronchial obstruction sustained-release drug and its preparation method, the specific implementation manner is the same as that of Example 1, the difference is that the cysteine-ciprofloxacin hydrochloride emulsion gel is prepared by Preparation Example 2.

[0076] Example 6

[0077] A veterinary anti-bronchial obstruction sustained-release drug and its preparation method, the specific implementation manner is the same as that of Example 1, the difference is that the cysteine-ciprofloxacin hydrochloride emulsion gel is prepared by Preparation Example 3.

[0078] Example 7

[0079] A veterinary anti-bronchial obstruction sustained-release drug and its preparation method, the specific implementation manner is the same as that of Example 1, the difference is that the roxithromycin-loaded modified silica is prepared by Preparation Example 5.

[0080] Example 8

[0081] A veterinary anti-bronchial obstruction sustained-release drug and its preparation method, the specific implementation manner is the same as that of Example 1, the difference is that the roxithromycin-loaded modified silica is prepared by Preparation Example 6.

[0082] Comparative Example 1

[0083] A veterinary anti-bronchial obstruction sustained-release drug and its preparation method, the specific implementation manner is the same as that of Example 1, the difference is that a mixture of 16 parts of cysteine and 16 parts of ciprofloxacin hydrochloride is used to replace 32 parts of cysteine-ciprofloxacin hydrochloride emulsion gel.

[0084] Comparative Example 2

[0085] A veterinary anti-bronchial obstruction sustained-release drug and its preparation method, the specific implementation manner is the same as that of Example 1, the difference is that an equal mass of roxithromycin is used to replace the roxithromycin-loaded modified silica.

[0086] Performance test:

[0087] (1) Acid-resistant sustained-release property: Using an ultraviolet spectrophotometer to track the release patterns of ciprofloxacin hydrochloride and roxithromycin in the sustained-release drug. Place 10 g of the sustained-release drug in 1000 mL of sodium dihydrogen phosphate buffer solution with pH = 2.5, shake it in a shaker at 40 °C at a rate of 100 rpm / min, and take samples at 5 h, 24 h, and 36 h respectively. Use an ultraviolet spectrophotometer to measure the absorbance of ciprofloxacin hydrochloride and roxithromycin, and calculate the release amount of ciprofloxacin hydrochloride according to the following formula:

[0088] Release amount of ciprofloxacin hydrochloride (%) = (W t / W0) × 100%;

[0089] where, W t is the drug content of ciprofloxacin hydrochloride in the buffer solution at t hours; W0 is the drug content of ciprofloxacin hydrochloride in the initial sample;

[0090] Since roxithromycin is unstable under acidic conditions, the release amount of roxithromycin is obtained by back-calculation:

[0091] Release amount of roxithromycin (%) = (M t -M0) / M0 × 100%;

[0092] where, M t is the content of roxithromycin in the remaining sample at t hours; M0 is the content of roxithromycin in the initial sample;

[0093] (2) Intestinal sustained-release property: The same test method as (1), the difference is that the pH of the sodium dihydrogen phosphate buffer solution is 6.5. According to the release amount calculation formula of ciprofloxacin hydrochloride, measure and calculate the release amount of ciprofloxacin hydrochloride, and calculate the release amount of roxithromycin with reference to the formula.

[0094] Test the sustained-release drugs of each example and comparative example according to the above test method, and the results are shown in Table 1:

[0095] Table 1

[0096]

[0097] Analysis of the experimental data in Table 1 shows that the sustained-release drugs prepared in Examples 1 to 4 have a low release rate in the simulated gastric acid buffer solution, can effectively resist gastric acid decomposition, and improve the drug absorption efficiency. In addition, the sustained-release effect is good at the simulated intestine and the duration is long. In Example 5, due to the change in the mass ratio of acetylcysteine, ciprofloxacin hydrochloride, ZnCl2 and water, acetylcysteine and ciprofloxacin hydrochloride cannot be effectively linked to alginic acid, resulting in a decrease in the gel coating efficiency, so that the sustained-release drug is released faster in the simulated gastric acid buffer solution and the simulated intestinal buffer solution. In Example 6, due to the change in the mass ratio of glycyrrhizic acid to alginic acid, the network structure is too dense, resulting in a decrease in the sustained-release performance of ciprofloxacin hydrochloride and a poor initial treatment effect. In Example 7, due to the change in the mass ratio of the mass of roxithromycin-loaded silica precursor to the mass of β-cyclodextrin, the initial sustained-release effect of roxithromycin becomes poor due to the increase in β-cyclodextrin, and the initial treatment effect becomes poor. In Example 8, due to the change in the mass ratio of the mass of roxithromycin-loaded silica precursor to the mass of β-cyclodextrin, the release amount of roxithromycin in the simulated gastric acid buffer solution increases due to the decrease in the content of β-cyclodextrin, which is not conducive to intestinal absorption. In Comparative Example 1, since a mixture of 16 parts of cysteine and 16 parts of ciprofloxacin hydrochloride is used to replace the cysteine-ciprofloxacin hydrochloride emulsion gel, it cannot play the role of sustained-release drug, and continuous administration is required in a short period, increasing the drug toxicity. In Comparative Example 1, since an equal mass of roxithromycin is used to replace roxithromycin-loaded modified silica, roxithromycin decomposes in gastric acid and cannot be effectively absorbed by the intestine, and a large amount of drug administration is still required to supplement the content of the drug absorbed by the intestine, increasing the drug toxicity.

[0098] The above examples are only used to illustrate the technical solutions of the present invention and are not intended to limit them; although the present invention has been described in detail with reference to the foregoing examples, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing examples, or perform equivalent replacements on some of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the various examples of the present invention.

Claims

1. A sustained-release veterinary drug for anti-bronchial obstruction, characterized in that, It comprises the following components in parts by mass: 30 - 34 parts of cysteine-ciprofloxacin hydrochloride emulsion gel, 3 - 6 parts of roxithromycin-loaded modified silica, 10 - 12 parts of sodium sulfate, and 20 - 25 parts of sodium chloride.

2. The veterinary anti-bronchial obstruction sustained-release drug according to claim 1, characterized in that, The sustained-release drug further comprises 60 - 70 parts of glucose.

3. The sustained-release veterinary drug for anti-bronchial obstruction according to claim 2, characterized in that, The preparation method of the cysteine-ciprofloxacin hydrochloride emulsion gel comprises the following steps: A1. Dissolve alginic acid in a 1 - 2 wt% acetic acid solution to prepare a 3 - 4 wt% alginic acid solution; A2. Mix acetylcysteine, ciprofloxacin hydrochloride, and ZnCl₂ with water to prepare a mixed aqueous solution; A3. Add the mixed aqueous solution in step A2 to the alginic acid solution in step A1, and finally add glycyrrhizic acid and stir evenly to obtain an emulsion gel.

4. The veterinary anti-bronchial obstruction sustained-release drug according to claim 3, characterized in that, In the mixed aqueous solution, the mass ratio of acetylcysteine, ciprofloxacin hydrochloride, ZnCl₂, and water is 1:(0.9 - 1.1):(4 - 6):(50 - 60).

5. The veterinary anti-bronchial obstruction sustained-release drug according to claim 3, characterized in that, The mass ratio of the alginic acid in step A1 to the acetylcysteine in step A2 is (3 - 4):

1.

6. The sustained-release veterinary drug for anti-bronchial obstruction according to claim 3, characterized in that, In step A3, the mass ratio of the glycyrrhizic acid to the alginic acid is 1:(1 - 1.2).

7. The veterinary anti-bronchial obstruction sustained-release drug according to claim 2, characterized in that, The preparation method of the roxithromycin-loaded modified silica comprises the following steps: S1. Mix silica and roxithromycin in ethanol, and concentrate and dry under reduced pressure to obtain a roxithromycin-loaded silica precursor; S2. Mix the roxithromycin-loaded silica precursor in step S1 with a saturated aqueous solution of β-cyclodextrin, stir, filter, and dry to obtain roxithromycin-loaded modified silica.

8. The veterinary anti-bronchial obstruction sustained-release drug according to claim 7, wherein The mass ratio of the silica to the roxithromycin is (1 - 3):

1.

9. The veterinary anti-bronchial obstruction sustained-release drug according to claim 7, characterized in that, In step S2, the mass ratio of the roxithromycin-loaded silica precursor to the mass of β-cyclodextrin is 1:(0.1 - 0.3).

10. A method for preparing the veterinary anti-bronchial obstruction sustained-release drug according to any one of claims 2 to 9, characterized in that, It comprises the following steps: Mix the cysteine-ciprofloxacin hydrochloride emulsion gel, roxithromycin-loaded silica, sodium sulfate, sodium chloride, and glucose evenly, dry, and seal and bag to obtain a veterinary anti-bronchial obstruction sustained-release drug.

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