Amoxicillin soluble powder for improving chicken survival rate and preparation method thereof

Abstract

The present invention belongs to the field of animal medicine technology, and specifically relates to an amoxicillin soluble powder for improving the survival rate of chickens and a preparation method thereof. The compound amoxicillin soluble powder prepared by the technical scheme of the present invention contains amoxicillin, potassium clavulanate, verbascoside, a stabilizer, a promoter and a lactose component. Animal experiments have shown that the curative effect of the amoxicillin soluble powder with verbascoside added is higher than that of the commercially available amoxicillin soluble powder; by screening the stabilizer and the promoter, the solubility and related substances of the product are better than the requirements of the current Chinese veterinary pharmacopoeia, and the product of the present invention is suitable for further expanded production.

Description

Technical Field

[0001] The invention belongs to the technical field of animal medicine, and particularly relates to an amoxicillin soluble powder for improving the survival rate of chickens and a preparation method thereof. Background Art

[0002] Amoxicillin is a broad-spectrum antibiotic widely used in veterinary medicine. It belongs to the β-lactam antibiotic class and has the ability to kill both Gram-negative and Gram-positive bacteria. Amoxicillin is an organic compound with the chemical formula C 16 H 19 N3O5S is an antibiotic drug, also known as amoxicillin, belonging to the aminopenicillin class of the penicillin family. It is a white or off-white crystalline powder with a slightly specific odor and bitter taste. It is the main variety of the second-generation penicillin. It is a broad-spectrum semi-synthetic antibiotic that can inhibit the synthesis of bacterial cell walls. It has a highly effective broad-spectrum antibacterial effect and very little toxic side effects. It is often used to treat bacterial infections such as middle ear infections, streptococcal pharyngitis, pneumonia, skin infections and urinary tract infections. The World Health Organization recommends this product as the preferred β-lactam oral antibiotic, and it occupies an important position in oral antibiotics.

[0003] Amoxicillin is mainly prepared as soluble powder in veterinary medicine, which is convenient for transportation and liquid preparation. The prior art of amoxicillin soluble powder discloses the following technical solutions: Chinese patent CN 107308116 A discloses a veterinary amoxicillin soluble powder, which contains: 50-70 parts of amoxicillin, 15-25 parts of cosolvent, 3-5 parts of β-cyclodextrin, 6-10 parts of microcrystalline cellulose, 2-3 parts of sodium tripolyphosphate, 1-3 parts of disodium ethylenediaminetetraacetate, 1-2 parts of sodium saccharin, and 2-4 parts of sucrose. The product has excellent properties of good stability, good water solubility, and high dissolution rate.

[0004] Chinese patent CN 107157936 A discloses an amoxicillin soluble powder and a preparation method thereof. The method uses amoxicillin as the main raw material, adds polyethylene glycol 6000 and β-cyclodextrin pretreated by heating dissolution and spray drying, and then mixes by equal amount incremental dilution method to obtain amoxicillin soluble powder with neutral and water-soluble properties that meets the requirements. The product was subjected to long-term sample retention inspection for 36 months under 25°C and relative humidity of 60%±10%, and there was no significant change in various inspection indicators. The auxiliary materials used in the present invention are simple and easy to obtain, the preparation method is simple, the product is soluble and stable, and it is suitable for industrial production.

[0005] Chinese patent CN 110522730 A provides an amoxicillin soluble powder, which contains: 30-65wt% amoxicillin trihydrate, 5-45wt% buffer, 5-45wt% water softener, 1-55wt% lactose, and 0.1-10wt% flavoring agent; the buffer can stabilize the pH of the solution after the amoxicillin soluble powder is dissolved between 6.5 and 8.0. The product has the advantages of good water solubility, good stability in water and gastric acid, and good palatability. Summary of the invention

[0006] The invention provides a compound soluble powder containing amoxicillin. By optimizing the prescription and optimizing the preparation method, verbascoside is added to improve the efficacy of amoxicillin, and an irreplaceable role is played in a chicken farm. Meanwhile, the process is further screened, and finally the solubility and stability of amoxicillin are improved, so that the powder is suitable for long-term storage.

[0007] Specifically, the technical solution of the present invention is achieved as follows: The first object of the present invention is to provide an amoxicillin soluble powder for improving the survival rate of chickens, calculated by weight ratio: The amoxicillin soluble powder for improving the survival rate of chickens is composed of: 10 parts of amoxicillin, 2.5 parts of potassium clavulanate, 1.5-4.5 parts of verbascoside, 1.4-7 parts of stabilizer, 0.6-2.4 parts of promoter, and 23.1-35 parts of lactose, wherein the promoter is polyethylene glycol 4000, polyvinyl alcohol, and calcium stearate, and the weight ratio is 3:2:1 respectively, and the stabilizer is thiosulfate, triethanolamine, and aluminum oxide, and the weight ratio is 1:2:4.

[0008] In one embodiment of the present invention, the composition of the amoxicillin soluble powder for improving the survival rate of chickens is calculated by weight: 10 parts of amoxicillin, 2.5 parts of potassium clavulanate, 2.5 parts of verbascoside, 3.5 parts of stabilizer, 1.2 parts of promoter, and 31.8 parts of lactose, wherein the promoter is polyethylene glycol 4000, polyvinyl alcohol, and calcium stearate, and the weight ratio is 3:2:1 respectively, and the stabilizer is thiosulfate, triethanolamine, and aluminum oxide, and the weight ratio is 1:2:4.

[0009] In one embodiment of the present invention, the composition of the amoxicillin soluble powder for improving the survival rate of chickens is calculated by weight: 10 parts of amoxicillin, 2.5 parts of potassium clavulanate, 5 parts of verbascoside, 7 parts of stabilizer, 2.4 parts of promoter, and 23.1 parts of lactose, wherein the promoter is polyethylene glycol 4000, polyvinyl alcohol, and calcium stearate, and the weight ratio is 3:2:1 respectively, and the stabilizer is thiosulfate, triethanolamine, and aluminum oxide, and the weight ratio is 1:2:4.

[0010] In one embodiment of the present invention, the composition of the amoxicillin soluble powder for improving the survival rate of chickens is calculated by weight: 10 parts of amoxicillin, 2.5 parts of potassium clavulanate, 1.5 parts of verbascoside, 1.4 parts of stabilizer, 0.6 parts of promoter, and 35 parts of lactose, wherein the promoter is polyethylene glycol 4000, polyvinyl alcohol, and calcium stearate, and the weight ratio is 3:2:1 respectively, and the stabilizer is thiosulfate, triethanolamine, and aluminum oxide, and the weight ratio is 1:2:4.

[0011] In one embodiment of the present invention, the thiosulfate can be selected from sodium thiosulfate.

[0012] In one embodiment of the present invention, the thiosulfate may be selected from potassium thiosulfate.

[0013] The second object of the present invention is to provide a method for preparing compound amoxicillin soluble powder, which specifically comprises the following steps: 1) Potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate are mixed in a three-dimensional motion mixer to obtain a mixture for later use; 2) Mix amoxicillin, thiosulfate and verbascoside evenly, add to buffer, evaporate to dryness, pass the mixture through a 100-mesh sieve, and set aside; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer to obtain a mixture for later use; 4) Transferring the mixture from step 3) to a vacuum drying oven, drying, crushing and sieving; 5) After testing, mix evenly with lactose, package according to dosage, and seal to obtain amoxicillin soluble powder that improves the survival rate of chickens.

[0014] Furthermore, the preparation method is preferably performed, comprising the following steps: 1) Place potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate in a three-dimensional motion mixer and mix for 30-40 minutes to obtain a mixture for later use; 2) Mix amoxicillin, thiosulfate and verbascoside evenly, add to citric acid-sodium citrate buffer with a pH value of 3.5-5.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 30-40 minutes to obtain a mixture for use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 75-85°C and 0.08MPa to a moisture content of 0.2%-0.5%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage, and seal to obtain amoxicillin soluble powder that improves the survival rate of chickens.

[0015] The third object of the present invention is to provide the use of the above-mentioned amoxicillin soluble powder for improving the survival rate of chickens in the preparation of antibiotic drugs. The use is used in treating sick chickens; further, the sick chickens are infected by Gram-negative bacteria.

[0016] Furthermore, the Gram-negative bacteria include any one or more of Escherichia coli, Proteus, Salmonella, Haemophilus, and Pasteurella brucella.

[0017] Compared with the prior art, the present invention has the following beneficial effects: The invention has the advantages that verbascoside is added to the amoxicillin tablet prescription, and the combined use thereof improves the efficacy of the amoxicillin soluble powder, and improves the ability to prevent Escherichia coli, Proteus, Salmonella, Haemophilus and Pasteurella brucella in chicken farms. Animal experiments have confirmed that the survival rate of chicks in the amoxicillin soluble powder with verbascoside added to the product is significantly improved, and the economic benefits of the chicken farm are significantly improved.

[0018] The amoxicillin soluble powder for improving the survival rate of chickens of the present invention preferably contains polyethylene glycol 4000, polyvinyl alcohol, calcium stearate, sodium thiosulfate, triethanolamine and aluminum oxide. Accelerated tests show that the pH value, solubility and content of related substances are better than those of the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 : Comparison chart of related substances of Examples 1-3 and Comparative Examples 4, 6 and 7 at 0-6 months.

[0020] Figure 2 : Comparison of therapeutic effects among negative control group, embodiment, comparative examples 1-3 and positive control group.

[0021] Figure 3 : Body weight comparison chart of negative control group, embodiment, comparative examples 1-3 and positive control group. DETAILED DESCRIPTION

[0022] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0023] Example 1: Amoxicillin soluble powder for improving chicken survival rate and its preparation method are as follows: The specific preparation method is: 1) Potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate are mixed in a three-dimensional motion mixer for 35 minutes to obtain a mixture for later use; 2) Mix amoxicillin, sodium thiosulfate and verbascoside evenly, add to citric acid-sodium citrate buffer with a pH value of 4.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 35 minutes to obtain a mixture for use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 80°C and 0.08MPa to a moisture content of 0.2%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage (50g per bag), and seal to obtain amoxicillin soluble powder that improves the survival rate of chickens.

[0024] Example 2: Amoxicillin soluble powder for improving chicken survival rate and its preparation method are as follows: The specific preparation method is: 1) Potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate are mixed in a three-dimensional motion mixer for 30 minutes to obtain a mixture for later use; 2) Mix amoxicillin, sodium thiosulfate and verbascoside evenly, add into citric acid-sodium citrate buffer with a pH value of 5.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) The mixture of step 1) and step 2) is then added with triethanolamine and aluminum oxide and mixed in a three-dimensional motion mixer for 30 minutes to obtain a mixture for use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 75°C and 0.08MPa to a moisture content of 0.5%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage (50g per bag), and seal to obtain amoxicillin soluble powder that improves the survival rate of chickens.

[0025] Example 3: Amoxicillin soluble powder for improving chicken survival rate and its preparation method are as follows: The specific preparation method is: 1) Potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate are mixed in a three-dimensional motion mixer for 40 minutes to obtain a mixture for later use; 2) Mix amoxicillin, sodium thiosulfate and verbascoside evenly, add to citric acid-sodium citrate buffer with a pH value of 3.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 40 minutes to obtain a mixture for later use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 85°C and 0.08MPa to a moisture content of 0.2%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage (50g per bag), and seal to obtain amoxicillin soluble powder that improves the survival rate of chickens.

[0026] Example 4: Amoxicillin soluble powder for improving chicken survival rate and its preparation method are as follows: The preparation process is the same as that of Example 1.

[0027] Example 5: Amoxicillin soluble powder for improving chicken survival rate and its preparation method are as follows: The preparation process is the same as that of Example 1.

[0028] Comparative Example 1: A compound amoxicillin soluble powder and preparation method thereof 1) Potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate are mixed in a three-dimensional motion mixer for 35 minutes to obtain a mixture for later use; 2) Mix amoxicillin, sodium thiosulfate and echinacoside evenly, add to citric acid-sodium citrate buffer with a pH value of 4.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 35 minutes to obtain a mixture for use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 80°C and 0.08MPa to a moisture content of 0.2%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage (50g per bag), and seal to obtain veterinary compound amoxicillin soluble powder.

[0029] Comparative Example 2: A compound amoxicillin soluble powder and a preparation method thereof The dosage of verbascoside is 0.2 kg, and the other ingredients, dosages and preparation methods are the same as those in Example 1.

[0030] Comparative Example 3: A compound amoxicillin soluble powder and preparation method thereof The dosage of verbascoside is 1.5 kg, and the other ingredients, dosages and preparation methods are the same as those in Example 1.

[0031] Comparative Example 4: A compound amoxicillin soluble powder and preparation method thereof The preparation method is as follows: The specific preparation method is: 1) Potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate are mixed in a three-dimensional motion mixer for 35 minutes to obtain a mixture for later use; 2) Mix amoxicillin, sodium metabisulfite and verbascoside evenly, add into citric acid-sodium citrate buffer with a pH value of 4.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) Add propanolamine and sodium tripolyphosphate to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 35 minutes to obtain a mixture for later use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 80°C and 0.08MPa to a moisture content of 0.2%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage (50g per bag), and seal to obtain veterinary compound amoxicillin soluble powder.

[0032] Comparative Example 5: A compound amoxicillin soluble powder and preparation method thereof The specific preparation method is: 1) Potassium clavulanate, diammonium hydrogen phosphate, sorbitol and L-cysteine ​​are mixed in a three-dimensional motion mixer for 35 minutes to obtain a mixture for use; 2) Mix amoxicillin, sodium thiosulfate and verbascoside evenly, add to citric acid-sodium citrate buffer with a pH value of 4.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 35 minutes to obtain a mixture for use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 80°C and 0.08MPa to a moisture content of 0.2%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage (50g per bag), and seal to obtain veterinary compound amoxicillin soluble powder.

[0033] Comparative Example 6: A compound amoxicillin soluble powder and preparation method thereof The specific preparation method is: 1) Potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate are mixed in a three-dimensional motion mixer for 35 minutes to obtain a mixture for later use; 2) Mix amoxicillin, sodium thiosulfate and verbascoside evenly, add to citric acid-sodium citrate buffer with a pH value of 4.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 35 minutes to obtain a mixture for use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 80°C and 0.08MPa to a moisture content of 0.2%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage (50g per bag), and seal to obtain veterinary compound amoxicillin soluble powder.

[0034] Comparative Example 7: A compound amoxicillin soluble powder and preparation method thereof The specific preparation method is: 1) Place amoxicillin, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate in a three-dimensional motion mixer and mix for 35 minutes to obtain a mixture for later use; 2) Mix potassium clavulanate, sodium thiosulfate and verbascoside evenly, add into acetic acid-sodium acetate buffer with pH value of 4.5, evaporate to dryness by rotary evaporation, pass the mixture through a 100-mesh sieve, and set aside; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 35 minutes to obtain a mixture for use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 80°C and 0.08MPa to a moisture content of 0.2%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage (50g per bag), and seal to obtain veterinary compound amoxicillin soluble powder.

[0035] 1. Solubility and pH value experiments Experimental method and condition requirements: Common dosage is based on the amoxicillin soluble powder in the Chinese Veterinary Pharmacopoeia. The dissolution and pH value of the amoxicillin soluble powder of Examples 1-5 and Comparative Examples 4-7 in tap water were mainly investigated.

[0036] Specific method: Weigh the soluble powders of Examples 1-5 and Comparative Examples 4-7, add water to make a solution containing 2 mg (in terms of amoxicillin) per 1 ml, determine the pH value according to the law, and record the dissolution time. Perform the above parallel test 5 times and take the average value.

[0037] Results: The dissolution and pH value of the amoxicillin soluble powders of Examples 1-3 and Comparative Examples 4-7 in tap water were investigated at 0, 1, 2, 3 and 6 months.

[0038] Acceleration conditions: Carry out the accelerated test at a temperature of 40°C ± 2°C and a relative humidity of 75% RH ± 5% RH, observe the dissolution of the sample and measure the pH value. The experimental results are shown in Table 1-2.

[0039] Table 1 Comparison of dissolution time of soluble powders of Examples 1-5 and Comparative Examples 4-7 under accelerated conditions Table 2 Comparison of pH values ​​of soluble powders of Examples 1-5 and Comparative Examples 4-7 under accelerated conditions 2. Relevant substances are determined by high performance liquid chromatography in accordance with the Chinese Pharmacopoeia (General Chapter 0512).

[0040] Mobile phase A: 0.05 mol / L phosphate buffer (take 0.05 mol / L potassium dihydrogen phosphate solution and adjust the pH value to 5.0 with 2 mol / L potassium hydroxide solution)-acetonitrile (99:1).

[0041] Mobile phase B: 0.05 mol / L phosphate buffer (pH 5.0)-acetonitrile (80:20).

[0042] Test solution: Take an appropriate amount of the soluble mixed powder of each embodiment of the present invention, accurately weigh it, add mobile phase A to dissolve it and quantitatively dilute it to make a solution containing about 1 ml of amoxicillin (according to C 16 H 19 N3O5S) 2.0 mg solution.

[0043] Reference solution: Take an appropriate amount of amoxicillin reference substance, weigh it accurately, add mobile phase A to dissolve it and quantitatively dilute it to make a solution containing about 1 ml of amoxicillin (according to C 16 H 19 N3O5S) 20μg solution.

[0044] System suitability solution: Take an appropriate amount of amoxicillin system suitability reference substance, dissolve it in mobile phase A and dilute it to make a solution containing approximately 2.0 mg per 1 ml.

[0045] Chromatographic conditions: octadecylsilane bonded silica gel was used as lactose; 0.05 mol / L phosphate buffer (take 0.05 mol / L potassium dihydrogen phosphate solution, adjust the pH value to 5.0 with 2 mol / L potassium hydroxide solution)-acetonitrile (99:1) was used as mobile phase A, and 0.05 mol / L phosphate buffer (pH5.0)-acetonitrile (80:20) was used as mobile phase B; firstly, mobile phase A-mobile phase B (92:8) was used for isocratic elution, and after the elution of amoxicillin peak was completed, linear gradient elution was performed immediately according to the table below; the detection wavelength was 254 nm; the injection volume was 20 μl.

[0046] Table 3 Chromatographic conditions Limits: If there are impurity peaks in the chromatogram of the test solution, the peak area shall be calculated by the main component external standard method. The single impurity shall not exceed 1.0%, and the total amount of impurities shall not exceed 3.0%. Peaks less than 0.05 times the main peak area of ​​the reference solution shall be ignored.

[0047] Test results: The contents of related substances of the amoxicillin soluble powder of Example 1 and Comparative Examples 4, 6, and 7 under accelerated conditions were investigated at 0, 1, 2, 3, and 6 months. Figure 1 .

[0048] 3. Drug efficacy experiment (1) Experimental animals: White-feathered broiler chicks aged 25 days old, weighing 1235±28 g, were randomly selected from a chicken farm of a certain enterprise in Weifang and were clinically diagnosed to be infected with Escherichia coli.

[0049] (2) Experimental grouping and administration method: 50 sick chickens infected with E. coli were selected and randomly divided into five groups, each with 10 chickens, namely: Example 1 group and Comparative Example 1-3 groups, a positive control group; and 10 healthy chicks were taken as a negative control group. There was no significant difference in body weight between the groups before the experiment ( P>0.05 ).

[0050] Administration method: Example 1 of the present invention (amoxicillin soluble powder prepared in Example 1), the positive control group (veterinary drug number 162061199, calculated according to the amoxicillin content) and comparative examples 1-3 (amoxicillin soluble powder prepared in comparative examples 1-3), 10 mg of compound amoxicillin soluble powder (calculated according to the amoxicillin content) was administered per 1 kg of body weight, once a day; the negative control group was given an equal dose of normal saline by gavage, once a day.

[0051] (3) Evaluation indicators: After the start of treatment, the weight changes of sick chickens and the distribution of dead animals were recorded daily. After 10 days of treatment, the treatment effect was statistically analyzed, including: Ineffective: refers to the situation that after 10 days, there is no obvious change in the symptoms of the diseased chickens, and they still maintain the symptoms before treatment or die.

[0052] Effective: It means that after 10 days, the symptoms of the diseased chickens have changed and are better than before treatment.

[0053] Cure: It means that after 10 days, the symptoms disappear and the sick chickens recover.

[0054] (4) Results analysis The analysis results were analyzed and statistically analyzed using GraphPad Prism 17.0. The specific statistical results are shown in Figure 2 and Figure 3 .

[0055] Figure 2 It can be seen that there were no deaths among the individuals in the negative control group, indicating that external factors other than drugs, such as the feeding environment, air quality, and diet, had no effect on the chicks; the ineffective individuals in comparison groups 1-3 all died within less than 10 days, and as for the cured individuals, the group in Example 1 was significantly higher than the positive control group.

[0056] Figure 3 The comparison of body weight and distribution shows that the combined use of amoxicillin and verbascoside improves the antibacterial effect of amoxicillin, and there is a significant difference compared with the comparative examples containing echinacoside or the content not within the technical solution of the present invention ( P<0.01), the inventors believe that there may be a synergistic effect between verbascoside and amoxicillin, and the combination of the two improves the antibacterial effect of amoxicillin, providing a therapeutic approach for resisting Gram-negative bacteria such as Escherichia coli, Proteus, Salmonella, Haemophilus, and Pasteurella brucella.

Claims

1. An amoxicillin soluble powder for improving the survival rate of chickens, characterized in that: Calculated by weight ratio, the composition of the amoxicillin soluble powder for improving the survival rate of chickens is: 10 parts of amoxicillin, 2.5 parts of potassium clavulanate, 1.5-4.5 parts of verbascoside, 1.4-7 parts of stabilizer, 0.6-2.4 parts of promoter, and 23.1-35 parts of lactose, wherein the promoter is polyethylene glycol 4000, polyvinyl alcohol, and calcium stearate, and the weight ratio is 3:2:1 respectively, and the stabilizer is thiosulfate, triethanolamine, and aluminum oxide, and the weight ratio is 1:2:

4.

2. The amoxicillin soluble powder for improving chicken survival rate according to claim 1, characterized in that: Calculated by weight ratio, the composition of the amoxicillin soluble powder for improving the survival rate of chickens is: 10 parts of amoxicillin, 2.5 parts of potassium clavulanate, 2.5 parts of verbascoside, 3.5 parts of stabilizer, 1.2 parts of promoter, and 31.8 parts of lactose, wherein the promoter is polyethylene glycol 4000, polyvinyl alcohol, and calcium stearate, and the weight ratio is 3:2:1 respectively, and the stabilizer is thiosulfate, triethanolamine, and aluminum oxide, and the weight ratio is 1:2:

4.

3. The amoxicillin soluble powder for improving chicken survival rate according to claim 1, characterized in that: Calculated by weight ratio, the composition of the amoxicillin soluble powder for improving the survival rate of chickens is: 10 parts of amoxicillin, 2.5 parts of potassium clavulanate, 5 parts of verbascoside, 7 parts of stabilizer, 2.4 parts of promoter, and 23.1 parts of lactose, wherein the promoter is polyethylene glycol 4000, polyvinyl alcohol, and calcium stearate, and the weight ratio is 3:2:1 respectively, and the stabilizer is thiosulfate, triethanolamine, and aluminum oxide, and the weight ratio is 1:2:

4.

4. The amoxicillin soluble powder for improving chicken survival rate according to claim 1, characterized in that: Calculated by weight ratio, the composition of the amoxicillin soluble powder for improving the survival rate of chickens is: 10 parts of amoxicillin, 2.5 parts of potassium clavulanate, 1.5 parts of verbascoside, 1.4 parts of stabilizer, 0.6 parts of promoter, and 35 parts of lactose, wherein the promoter is polyethylene glycol 4000, polyvinyl alcohol, and calcium stearate, and the weight ratio is 3:2:1 respectively, and the stabilizer is sodium thiosulfate, triethanolamine, and aluminum oxide, and the weight ratio is 1:2:

4.

5. The amoxicillin soluble powder for improving chicken survival rate according to claim 1, characterized in that: The thiosulfate is any one of sodium thiosulfate and potassium thiosulfate.

6. A method for preparing the amoxicillin soluble powder for improving chicken survival rate according to any one of claims 1 to 5, characterized in that: The preparation method comprises the following steps: 1) Potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate are mixed in a three-dimensional motion mixer to obtain a mixture for later use; 2) Mix amoxicillin, thiosulfate and verbascoside evenly, add to buffer, evaporate to dryness, pass the mixture through a 100-mesh sieve, and set aside; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer to obtain a mixture for later use; 4) Transferring the mixture from step 3) to a vacuum drying oven, drying, crushing and sieving; 5) After testing, mix evenly with lactose, package according to dosage, and seal to obtain amoxicillin soluble powder that improves the survival rate of chickens.

7. The method according to claim 6, characterized in that The method comprises the following steps: 1) Place potassium clavulanate, polyethylene glycol 4000, polyvinyl alcohol and calcium stearate in a three-dimensional motion mixer and mix for 30-40 minutes to obtain a mixture for later use; 2) Mix amoxicillin, thiosulfate and verbascoside evenly, add to citric acid-sodium citrate buffer with a pH value of 3.5-5.5, evaporate to dryness by rotary evaporation, and pass the mixture through a 100-mesh sieve to obtain a mixture for later use; 3) Add triethanolamine and aluminum oxide to the mixture of step 1) and step 2) and mix in a three-dimensional motion mixer for 30-40 minutes to obtain a mixture for use; 4) Transfer the mixture of step 3) to a vacuum drying oven, dry it at 75-85°C and 0.08MPa to a moisture content of 0.2%-0.5%, and grind it through a 100-mesh sieve; 5) After testing, mix evenly with lactose, package according to dosage, and seal to obtain amoxicillin soluble powder that improves the survival rate of chickens.

8. Use of the amoxicillin soluble powder for improving the survival rate of chickens as claimed in any one of claims 1 to 5 in treating sick chickens.

9. The use according to claim 8, characterized in that The diseased chickens were infected by Gram-negative bacteria.

10. The use according to claim 9, characterized in that The Gram-negative bacteria are any one or more of Escherichia coli, Proteus, Salmonella, Haemophilus, and Pasteurella brucella.

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