Veterinary anti-infective amoxicillin formulations and methods of making same

Abstract

The present application belongs to the animal medicine technical field, and particularly relates to a veterinary anti-infection amoxicillin preparation and a preparation method thereof. The preparation prepared by using the technical scheme of the present application contains amoxicillin, chlorpheniramine maleate, usnic acid, a stabilizer and a D-cannasugar component. It is found through an accelerated test that the amoxicillin preparation has higher stability and activity, and the product of the present application is suitable for further expanded production.

Description

Technical Field

[0001] This invention belongs to the field of animal medicine technology, specifically relating to amoxicillin preparations for veterinary anti-infective use and their preparation methods. Background Technology

[0002] Amoxicillin is a broad-spectrum antibiotic widely used in veterinary medicine. It belongs to the β-lactam antibiotic class and is effective against both Gram-negative and Gram-positive bacteria. Amoxicillin is an organic compound with the chemical formula C0. 16 H 19 N3O5S is an antibiotic, 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 characteristic odor and bitter taste. It is a major type of second-generation penicillin, a broad-spectrum semi-synthetic antibiotic that inhibits bacterial cell wall synthesis. It has highly effective broad-spectrum antibacterial activity with minimal side effects and is commonly used to treat bacterial infections such as middle ear infections, streptococcal laryngitis, pneumonia, skin infections, and urinary tract infections. The World Health Organization recommends it as a first-line β-lactam oral antibiotic, giving it an important place among oral antibiotics.

[0003] Chlorpheniramine maleate, also known as chlorpheniramine, is a histamine antagonist. It counteracts the allergic effects of histamine by competing with histamine H1 receptors; however, it does not affect histamine metabolism or prevent histamine release. Chlorpheniramine also has anticholinergic M receptor activity, acting on cholinergic mycosis receptors, causing nasal mucosal dryness. Clinically, it is mainly used to treat allergic rhinitis and skin and mucous membrane allergies. Summary of the Invention

[0004] This invention provides a compound preparation containing amoxicillin. Through formulation optimization and preparation method optimization, the addition of isoflavones enhances the efficacy of amoxicillin. At the same time, further screening of the process ultimately improves the dissolution and stability of amoxicillin, making it suitable for long-term storage.

[0005] Specifically, the technical solution of the present invention is implemented as follows: A veterinary amoxicillin preparation, by weight, comprises: 1-10 parts amoxicillin, 0.05-0.5 parts chlorpheniramine maleate, 0.1-2.0 parts usnic acid, 82.5-98.5 parts diluent, and 1.0-5.0 parts D-ginkgo. Further, in a preferred embodiment of the present invention, the veterinary amoxicillin preparation comprises, by weight: 5.5 parts amoxicillin, 0.25 parts chlorpheniramine maleate, 0.85 parts usnic acid, 90.4 parts diluent, and 3.0 parts D-ginkgo. Furthermore, in a preferred embodiment of the present invention, the veterinary amoxicillin preparation is composed of the following components by weight: 10 parts amoxicillin, 0.5 parts chlorpheniramine maleate, 2 parts usnic acid, 82.5 parts diluent, and 5 parts D-ginkgolide, wherein the diluent is composed of a mixture of sucrose and dextrin in a weight ratio of 1:1.5.

[0006] Further, the diluent is selected from at least one of lactose, starch, dextrin, sucrose, glucose, calcium carbonate, kaolin, and microcrystalline cellulose. In a preferred embodiment of the present invention, the diluent is composed of a mixture of sucrose and dextrin in a weight ratio of 1:0.5-1.5. In the most preferred embodiment of the present invention, the diluent is composed of a mixture of sucrose and dextrin in a weight ratio of 1:1.

[0007] The veterinary amoxicillin preparation of the present invention is further preferably a compound amoxicillin soluble powder. The powder is convenient to use and transport, and can be used for 2 years or even more than 3 years.

[0008] Furthermore, the preparation of the veterinary amoxicillin formulation includes the following steps: (1) Mix amoxicillin and usnic acid in proportion, add an appropriate amount of tartaric acid buffer solution to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and sieve to make amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of tartaric acid buffer solution to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix. (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and then package.

[0009] Furthermore, the preparation of the amoxicillin formulation includes the following steps: (1) Mix amoxicillin and usnic acid in proportion, add an appropriate amount of tartaric acid buffer solution with pH value of 4.0-5.0 to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and pass through an 80-100 mesh sieve to prepare amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of tartaric acid buffer solution with pH 4.2-4.8 to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and pass through an 80-100 mesh sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix. (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and package to obtain veterinary amoxicillin preparation.

[0010] The application of the veterinary amoxicillin preparation in the treatment of diseased chickens.

[0011] The invention is characterized by the highly effective combined use of amoxicillin and chlorpheniramine maleate, which improves the ability of chicken farms, especially broiler chickens, to prevent Escherichia coli, Proteus, Salmonella, Haemophilus, and Brucella, increases the survival rate of chicks, and improves the economic benefits of chicken farms. Attached Figure Description

[0012] Figure 1 Dissolution rates of amoxicillin in Examples 1-3 and Comparative Examples 5-6 at month 0.

[0013] Figure 2 Dissolution rates of chlorpheniramine maleate in Examples 1-3 and Comparative Examples 5-6 at month 0.

[0014] Figure 3 Dissolution rates of amoxicillin in Examples 1-3 and Comparative Examples 5-6 at month 6 after accelerated testing.

[0015] Figure 4 Following accelerated testing, the dissolution rates of chlorpheniramine maleate in Examples 1-3 and Comparative Examples 5-6 at month 6 were compared.

[0016] Figure 5 The amoxicillin content in Examples 1-3, Comparative Examples 1-2, and Comparative Examples 5-6 in the first month, second month, third month, and sixth month.

[0017] Figure 6 The content of chlorpheniramine maleate in Examples 1-3 and Comparative Examples 1-4 in the 1st month, 2nd month, 3rd month and 6th month. Detailed Implementation

[0018] To make the objectives and technical solutions of this invention clearer, the following embodiments are provided for further explanation. However, the scope of protection of this invention is not limited to these embodiments; the embodiments are merely for illustrative purposes. Those skilled in the art should understand that any changes or equivalent substitutions that do not depart from the concept of this invention are included within the scope of protection of this invention.

[0019] Example 1: The preparation of an amoxicillin-containing formulation is as follows: Amoxicillin 1kg, Chlorpheniramine Maleate 0.05kg, Usnea Citrate 0.1kg, D-Ginane 1kg, Diluent (composed of a mixture of sucrose and dextrin in a weight ratio of 1:0.5) 97.85kg.

[0020] (1) Mix amoxicillin and usnic acid in the above proportion, add an appropriate amount of tartaric acid buffer solution with pH 4.0 to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and pass through an 80-100 mesh sieve to prepare amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of tartaric acid buffer solution with pH 4.2 to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and pass through an 80-100 mesh sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix. (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and package to obtain veterinary amoxicillin preparation.

[0021] Example 2: The preparation of an amoxicillin-containing formulation is as follows: Amoxicillin 10kg, Chlorpheniramine Maleate 0.5kg, Usnea Citrate 2kg, D-Cinnamon 5kg, Diluent (composed of a mixture of sucrose and dextrin in a weight ratio of 1:1.5) 82.5kg.

[0022] (1) Mix amoxicillin and usnic acid in the above proportion, add an appropriate amount of tartaric acid buffer solution with pH 5.0 to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and pass through an 80-100 mesh sieve to prepare amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of tartaric acid buffer solution with pH 4.8 to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and pass through an 80-100 mesh sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix. (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and package to obtain veterinary amoxicillin preparation.

[0023] Example 3: The preparation of an amoxicillin-containing formulation is as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, Usnea Citrate 0.85kg, D-Ginane 3kg, Diluent (composed of a mixture of sucrose and dextrin in a 1:1 weight ratio) 90.4kg.

[0024] (1) Mix amoxicillin and usnic acid in the above proportion, add an appropriate amount of tartaric acid buffer solution with pH value of 4.0-5.0 to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and pass through an 80-100 mesh sieve to prepare amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of tartaric acid buffer solution with pH 4.2-4.8 to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and pass through an 80-100 mesh sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix. (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and package to obtain veterinary amoxicillin preparation.

[0025] Example 4: The preparation of an amoxicillin-containing formulation is as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, Usnea Citrate 0.85kg, D-Ginane 3kg, Lactose 90.4kg.

[0026] Example 5: The preparation of an amoxicillin-containing formulation is as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, Usnea Citrate 0.85kg, D-Ginane 3kg, Microcrystalline Cellulose 90.4kg.

[0027] Example 6: The preparation of an amoxicillin-containing formulation is as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, Usnea Citrate 0.85kg, D-Ginane 3kg, Diluent (composed of a mixture of glucose and calcium carbonate in a 1:1 weight ratio) 90.4kg.

[0028] Comparative Example 1: A formulation containing amoxicillin was prepared as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, D-Ginane 3kg, Diluent (composed of a mixture of sucrose and dextrin in a 1:1 weight ratio) 91.25kg.

[0029] Comparative Example 2: A formulation containing amoxicillin was prepared as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, Glycine 0.85kg, D-Ginane 3kg, Diluent (composed of a mixture of sucrose and dextrin in a 1:1 weight ratio) 90.4kg.

[0030] Comparative Example 3: A formulation containing amoxicillin was prepared as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, Usnea C 0.85kg, D-xylose 3kg, Diluent (composed of a mixture of sucrose and dextrin in a 1:1 weight ratio) 90.4kg.

[0031] Comparative Example 4: A formulation containing amoxicillin was prepared as follows: Amoxicillin 5.5kg, chlorpheniramine maleate 0.25kg, usnic acid 0.85kg, diluent (composed of a mixture of sucrose and dextrin in a 1:1 weight ratio) 93.4kg.

[0032] Comparative Example 5: A formulation containing amoxicillin was prepared as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, Usnea Citrate 0.05kg, D-Ginane 6kg, Diluent (composed of a mixture of sucrose and dextrin in a 1:1 weight ratio) 88.2kg.

[0033] Comparative Example 6: A formulation containing amoxicillin was prepared as follows: Amoxicillin 5.5kg, Chlorpheniramine Maleate 0.25kg, Usnea Citrate 0.85kg, D-Ginane 3kg, Diluent (composed of a mixture of sucrose and dextrin in a 1:1 weight ratio) 90.4kg.

[0034] (1) Mix amoxicillin and usnic acid in the above proportion, add an appropriate amount of water to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and pass through an 80-100 mesh sieve to prepare amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of water to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and pass through an 80-100 mesh sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix; (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and package to obtain veterinary amoxicillin preparation.

[0035] 1. Method for determining amoxicillin content [Content Determination] Determined by high performance liquid chromatography (General Rule 0512).

[0036] Test solution: Take an appropriate amount of this product (approximately equivalent to amoxicillin, according to C) 16 H 19 Weigh 25 mg of N3O5S accurately, place it in a 50 mL volumetric flask, add the mobile phase to dissolve and dilute to the mark, and shake well.

[0037] Reference solution: Accurately weigh an appropriate amount of amoxicillin reference standard, dissolve and quantitatively dilute it in the mobile phase to prepare a solution containing approximately amoxicillin per 1 mL (according to C). 16 H 19 A solution containing 0.5 mg of N3O5S.

[0038] System suitability solution: Take 25 mg of amoxicillin system suitability reference standard, place it in a 50 mL volumetric flask, add mobile phase to dissolve and dilute to the mark, and shake well.

[0039] Chromatographic conditions: Octadecylsilane-bonded silica gel was used as the stationary phase; 0.05 mol / L potassium dihydrogen phosphate solution (pH adjusted to 5.0 with 2 mol / L potassium hydroxide solution) - acetonitrile (97.5:2.5) was used as the mobile phase; the detection wavelength was 254 nm; the injection volume was 20 μL. System suitability requirements: The chromatogram of the system suitability solution should be consistent with the standard chromatogram.

[0040] Assay: Accurately measure the test solution and reference solution, inject them separately into the liquid chromatograph, and record the chromatograms. Calculate the results based on peak area using the external standard method.

[0041] 2. Method for determining the content of chlorpheniramine maleate [Content Determination] Accurately weigh approximately 0.15 g of this product, dissolve it in 10 mL of glacial acetic acid, add 1 drop of crystal violet indicator, and titrate with perchloric acid titrant (0.1 mol / L) until the solution turns blue-green. Correct the titration result with a blank test. Each 1 mL of perchloric acid titrant (0.1 mol / L) is equivalent to 19.54 mg of C. 16 H 19 ClN2·C4H4O4.

[0042] 4. Methods for determining dissolution rate Dissolution method: basket method, 50 rpm; Dissolution medium: pH=6.8; 5. Accelerated testing After packaging, the amoxicillin preparation was placed at a temperature of 40±2℃ and a relative humidity of 75%±5% for 6 months. Samples were taken at the end of the first, second, third and sixth months of the test period to determine the contents of amoxicillin and chlorpheniramine maleate.

[0043] 6. Measurement Results 1) Dissolution Figure 1 Dissolution rates of amoxicillin in Examples 1-3 and Comparative Examples 5-6 at month 0.

[0044] Figure 2 Dissolution rates of chlorpheniramine maleate in Examples 1-3 and Comparative Examples 5-6 at month 0.

[0045] Figure 3 Following accelerated testing, the dissolution rates of amoxicillin in Examples 1-3 and Comparative Examples 5-6 at month 0 were compared.

[0046] Figure 4Following accelerated testing, the dissolution rates of chlorpheniramine maleate in Examples 1-3 and Comparative Examples 5-6 at month 0 were compared.

[0047] 2) Content Figure 5 The amoxicillin content in Examples 1-3, Comparative Examples 1-2, and Comparative Examples 5-6 in the first month, second month, third month, and sixth month.

[0048] Figure 6 The content of chlorpheniramine maleate in Examples 1-3 and Comparative Examples 1-4 in the 1st month, 2nd month, 3rd month and 6th month.

[0049] pass Figures 1-6 It can be seen that the dissolution rate and content of chlorpheniramine maleate and amoxicillin in Examples 1-3 are significantly better than those in Comparative Examples 1-6.

Claims

1. A veterinary amoxicillin preparation, characterized in that, The veterinary amoxicillin preparation, by weight ratio, comprises: 1-10 parts amoxicillin, 0.05-0.5 parts chlorpheniramine maleate, 0.1-2.0 parts usnic acid, 82.5-98.5 parts diluent, and 1.0-5.0 parts D-ginkgolide. The preparation comprises the following steps: (1) Mix amoxicillin and usnic acid in proportion, add an appropriate amount of tartaric acid buffer solution to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and sieve to make amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of tartaric acid buffer solution to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix. (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and then package.

2. The veterinary amoxicillin preparation according to claim 1, characterized in that, The diluent is selected from at least one of lactose, starch, dextrin, sucrose, glucose, calcium carbonate, kaolin, and microcrystalline cellulose; preferably, the diluent is selected from a mixture of sucrose and dextrin.

3. The veterinary amoxicillin preparation according to claim 1, characterized in that, The veterinary amoxicillin preparation, by weight ratio, comprises: 5.5 parts amoxicillin, 0.25 parts chlorpheniramine maleate, 0.85 parts usnic acid, 90.4 parts diluent, and 3.0 parts D-ginkgoside, wherein the diluent is a mixture of sucrose and dextrin in a weight ratio of 1:0.5-1.

5.

4. The veterinary amoxicillin preparation according to claim 1, characterized in that, The veterinary amoxicillin preparation, by weight ratio, comprises: 10 parts amoxicillin, 0.5 parts chlorpheniramine maleate, 2 parts usnic acid, 82.5 parts diluent, and 5 parts D-ginkgoside, wherein the diluent is a mixture of sucrose and dextrin in a weight ratio of 1:1.

5.

5. The veterinary amoxicillin preparation according to claim 1, characterized in that, The veterinary amoxicillin preparation is a compound amoxicillin soluble powder or a compound amoxicillin suspension.

6. The veterinary amoxicillin preparation according to claim 1, characterized in that, The preparation of the amoxicillin formulation includes the following steps: (1) Mix amoxicillin and usnic acid in proportion, add an appropriate amount of tartaric acid buffer solution to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and sieve to make amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of tartaric acid buffer solution to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix. (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and then package.

7. The veterinary amoxicillin preparation according to claim 1, characterized in that, The preparation of the amoxicillin formulation includes the following steps: (1) Mix amoxicillin and usnic acid in proportion, add an appropriate amount of tartaric acid buffer solution with pH value of 4.0-5.0 to moisten, grind and mix thoroughly, dry at low temperature, pulverize again, and pass through an 80-100 mesh sieve to prepare amoxicillin-usnic acid premix. (2) Mix chlorpheniramine maleate and D-ginkengose, add an appropriate amount of tartaric acid buffer solution with pH 4.2-4.8 to moisten, grind and mix thoroughly, dry at low temperature, pulverize, and pass through an 80-100 mesh sieve to prepare chlorpheniramine maleate-D-ginkengose ​​premix. (3) Mix the premix from step (1) with the premix from step (2) until uniform; add diluent to make up to the full amount, mix until uniform by equal increment method, and package to obtain veterinary amoxicillin preparation.

8. The use of the veterinary amoxicillin preparation as described in any one of claims 1-5 in the treatment of diseased chickens.

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