Ciprofloxacin lactate injection and preparation method thereof

Abstract

The application discloses a ciprofloxacin lactate injection and a preparation method thereof, and relates to the field of veterinary drugs.The preparation method is as follows: S1: 80v / v% of total dosage of water for injection is weighed, and then sodium sulfite, sodium chloride and ciprofloxacin lactate are sequentially added and stirred to completely dissolve; lactic acid is used to adjust the pH value to 3.8-4.0 to obtain a concentrated solution; S2: the concentrated solution is coarsely filtered to obtain a filtrate; S3: water for injection is added into the filtrate to a specified volume, lactic acid is added to adjust the pH value, the mixture is uniformly stirred, and the mixture is refined, sterilized and prepared.The surface of the material obtained by high-temperature carbonization of the freeze-dried chitosan during the coarse filtration contains a large number of amino groups, can complex metal ions possibly mixed in the injection, and greatly improves the stability of the injection.

Description

Technical Field

[0001] This invention relates to the field of veterinary drugs, specifically to a ciprofloxacin lactate injection and its preparation method. Background Technology

[0002] With the development of animal husbandry, animals are playing an increasingly larger role in the livestock structure, leading to the occurrence of various animal diseases and necessitating further research into veterinary drugs. Ciprofloxacin lactate, a third-generation fluoroquinolone antibiotic, is widely used to treat bacterial infections in livestock and poultry. However, traditional formulations suffer from problems such as frequent use, significant stress responses, and the development of drug resistance. Furthermore, while ciprofloxacin lactate is readily soluble in water, its aqueous solution exhibits poor stability. Therefore, the development of a long-acting and stable injectable solution has become an industry requirement. Summary of the Invention

[0003] The purpose of this invention is to at least solve one of the technical problems existing in the prior art, and to provide a ciprofloxacin lactate injection and its preparation method.

[0004] The technical solution of the present invention is as follows: A method for preparing ciprofloxacin lactate injection includes the following steps: S1: Weigh 70-80% of the total volume of water for injection, then add sodium sulfite, sodium chloride, and ciprofloxacin lactate in sequence, and stir until completely dissolved; adjust the pH to 3.8-4.0 with lactic acid to obtain the concentrated solution; S2: The concentrated solution is coarsely filtered to obtain the filtrate; S3: Add water for injection to the filtrate to the specified volume, add lactic acid to adjust the pH, stir evenly, filter finely, sterilize, and obtain the product.

[0005] Preferably, in step S2, modified activated carbon is used for adsorption during coarse filtration, followed by filtration. The modified activated carbon is prepared as follows: Chitosan was dissolved in water to obtain a chitosan suspension. The suspension was stirred, and then acetic acid and β-cyclodextrin were added and mixed to obtain a chitosan aqueous solution. The chitosan aqueous solution was then freeze-dried, removed, carbonized under an inert gas, and cooled to obtain the final product.

[0006] Preferably, the carbonization temperature is 800-1000℃ and the carbonization time is 60-100min.

[0007] Preferably, the mass concentration of the acetic acid is 0.01-0.03 mol / L.

[0008] Preferably, the inert gas is nitrogen.

[0009] Preferably, the freeze-drying temperature is -5°C to -20°C, and the freezing time is 20-60 minutes.

[0010] Preferably, in step S3, the fine filtration uses a pH of 0.20-0.24. m filter element.

[0011] Preferably, in step S3, the sterilization conditions are: sterilization temperature of 121°C and sterilization time of 30 minutes.

[0012] A ciprofloxacin lactate injection solution is prepared using the above-described preparation method.

[0013] The beneficial effects of this invention are as follows: The ciprofloxacin lactate injection prepared by this invention has a large amount of amino groups on its surface obtained by using freeze-dried chitosan during coarse filtration and high-temperature carbonization. These amino groups can complex metal ions that may be mixed in the injection, greatly improving the stability of the injection. At the same time, combined with β-cyclodextrin, it has stable solubilization at different temperatures, greatly improving the stability of the injection at low and high temperatures. Detailed Implementation

[0014] The embodiments of the present invention are described in detail below. These embodiments are exemplary and are only used to explain the present invention, and should not be construed as limiting the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the art or according to the product instructions. Reagents or instruments used, unless otherwise specified, are all commercially available conventional products.

[0015] Example 1 Each 1000ml of injection solution contains 50g of ciprofloxacin lactate, 9g of sodium chloride, 2g of sodium bisulfite, lactic acid, and the remainder is water for injection.

[0016] The preparation method is as follows: S1: Weigh 80% of the total volume of water for injection, then add sodium sulfite, sodium chloride, and ciprofloxacin lactate in sequence, and stir until completely dissolved; adjust the pH to 3.8-4.0 with lactic acid to obtain the concentrated solution; S2: The concentrated solution is coarsely filtered to obtain the filtrate; S3: Add water for injection to the filtrate to the specified volume, add lactic acid to adjust the pH, stir evenly, filter finely, sterilize, and obtain the product.

[0017] In step S2, modified activated carbon is used for adsorption during coarse filtration, followed by filtration. The modified activated carbon is prepared as follows: Chitosan was dissolved in water to obtain a chitosan suspension, which was stirred, and then acetic acid and β-cyclodextrin were added and mixed well to obtain a 3 g / L chitosan aqueous solution. The chitosan aqueous solution was then freeze-dried, removed, carbonized under an inert gas, and cooled to obtain the final product. The mass ratio of β-cyclodextrin to chitosan was 1:5.

[0018] The carbonization temperature is 1000℃ and the carbonization time is 60min.

[0019] The mass concentration of the acetic acid is 0.02 mol / L.

[0020] The inert gas is nitrogen.

[0021] The freeze-drying temperature is -15℃ and the freezing time is 40 minutes.

[0022] In step S3, the fine filtration uses 0.24 m filter element.

[0023] In step S3, the sterilization conditions are: sterilization temperature of 121°C and sterilization time of 30 minutes.

[0024] Example 2 Each 1000ml of injection solution contains 50g of ciprofloxacin lactate, 9g of sodium chloride, 2g of sodium bisulfite, lactic acid, and the remainder is water for injection.

[0025] The preparation method is as follows: S1: Weigh 80% of the total volume of water for injection, then add sodium sulfite, sodium chloride, and ciprofloxacin lactate in sequence, and stir until completely dissolved; adjust the pH to 3.8-4.0 with lactic acid to obtain the concentrated solution; S2: The concentrated solution is coarsely filtered to obtain the filtrate; S3: Add water for injection to the filtrate to the specified volume, add lactic acid to adjust the pH, stir evenly, filter finely, sterilize, and obtain the product.

[0026] In step S2, modified activated carbon is used for adsorption during coarse filtration, followed by filtration. The modified activated carbon is prepared as follows: Chitosan was dissolved in water to obtain a chitosan suspension, which was stirred, and then acetic acid and β-cyclodextrin were added and mixed well to obtain a 3 g / L chitosan aqueous solution. The chitosan aqueous solution was then freeze-dried, removed, carbonized under an inert gas, and cooled to obtain the final product. The mass ratio of β-cyclodextrin to chitosan was 1:5.

[0027] The carbonization temperature is 900℃ and the carbonization time is 80min.

[0028] The mass concentration of the acetic acid is 0.02 mol / L.

[0029] The inert gas is nitrogen.

[0030] The freeze-drying temperature is -20℃ and the freezing time is 30 minutes.

[0031] In step S3, the fine filtration uses 0.20... m filter element.

[0032] In step S3, the sterilization conditions are: sterilization temperature of 121°C and sterilization time of 30 minutes.

[0033] Example 3 Each 1000ml of injection solution contains 50g of ciprofloxacin lactate, 9g of sodium chloride, 2g of sodium bisulfite, lactic acid, and the remainder is water for injection.

[0034] The preparation method is as follows: S1: Weigh 80% of the total volume of water for injection, then add sodium sulfite, sodium chloride, and ciprofloxacin lactate in sequence, and stir until completely dissolved; adjust the pH to 3.8-4.0 with lactic acid to obtain the concentrated solution; S2: The concentrated solution is coarsely filtered to obtain the filtrate; S3: Add water for injection to the filtrate to the specified volume, add lactic acid to adjust the pH, stir evenly, filter finely, sterilize, and obtain the product.

[0035] In step S2, modified activated carbon is used for adsorption during coarse filtration, followed by filtration. The modified activated carbon is prepared as follows: Chitosan was dissolved in water to obtain a chitosan suspension, which was stirred, and then acetic acid and β-cyclodextrin were added and mixed well to obtain a 3 g / L chitosan aqueous solution. The chitosan aqueous solution was then freeze-dried, removed, carbonized under an inert gas, and cooled to obtain the final product. The mass ratio of β-cyclodextrin to chitosan was 1:5.

[0036] The carbonization temperature is 1000℃ and the carbonization time is 80min.

[0037] The mass concentration of the acetic acid is 0.03 mol / L.

[0038] The inert gas is nitrogen.

[0039] The freeze-drying temperature is -20℃ and the freezing time is 30 minutes.

[0040] In step S3, the fine filtration uses 0.24 m filter element.

[0041] In step S3, the sterilization conditions are: sterilization temperature of 121°C and sterilization time of 30 minutes.

[0042] Example 4 Each 1000ml of injection solution contains 50g of ciprofloxacin lactate, 9g of sodium chloride, 2g of sodium bisulfite, lactic acid, and the remainder is water for injection.

[0043] The preparation method is as follows: S1: Weigh 80% of the total volume of water for injection, then add sodium sulfite, sodium chloride, and ciprofloxacin lactate in sequence, and stir until completely dissolved; adjust the pH to 3.8-4.0 with lactic acid to obtain the concentrated solution; S2: The concentrated solution is coarsely filtered to obtain the filtrate; S3: Add water for injection to the filtrate to the specified volume, add lactic acid to adjust the pH, stir evenly, filter finely, sterilize, and obtain the product.

[0044] In step S2, modified activated carbon is used for adsorption during coarse filtration, followed by filtration. The modified activated carbon is prepared as follows: Chitosan was dissolved in water to obtain a chitosan suspension, which was stirred, and then acetic acid and β-cyclodextrin were added and mixed well to obtain a 3 g / L chitosan aqueous solution. The chitosan aqueous solution was then freeze-dried, removed, carbonized under an inert gas, and cooled to obtain the final product. The mass ratio of β-cyclodextrin to chitosan was 1:5.

[0045] The carbonization temperature is 850℃ and the carbonization time is 80min.

[0046] The mass concentration of the acetic acid is 0.03 mol / L.

[0047] The inert gas is nitrogen.

[0048] The freeze-drying temperature is -20℃ and the freezing time is 30 minutes.

[0049] In step S3, the fine filtration uses 0.24 m filter element.

[0050] In step S3, the sterilization conditions are: sterilization temperature of 121°C and sterilization time of 30 minutes.

[0051] Example 5 Each 1000ml of injection solution contains 50g of ciprofloxacin lactate, 9g of sodium chloride, 2g of sodium bisulfite, lactic acid, and the remainder is water for injection.

[0052] The preparation method is as follows: S1: Weigh 80% of the total volume of water for injection, then add sodium sulfite, sodium chloride, and ciprofloxacin lactate in sequence, and stir until completely dissolved; adjust the pH to 3.8-4.0 with lactic acid to obtain the concentrated solution; S2: The concentrated solution is coarsely filtered to obtain the filtrate; S3: Add water for injection to the filtrate to the specified volume, add lactic acid to adjust the pH, stir evenly, filter finely, sterilize, and obtain the product.

[0053] In step S2, modified activated carbon is used for adsorption during coarse filtration, followed by filtration. The modified activated carbon is prepared as follows: Chitosan was dissolved in water to obtain a chitosan suspension, which was stirred, and then acetic acid and β-cyclodextrin were added and mixed well to obtain a 5 g / L chitosan aqueous solution. The chitosan aqueous solution was then freeze-dried, removed, carbonized under an inert gas, and cooled to obtain the final product. The mass ratio of β-cyclodextrin to chitosan was 1:5.

[0054] The carbonization temperature is 950℃ and the carbonization time is 80min.

[0055] The mass concentration of the acetic acid is 0.03 mol / L.

[0056] The inert gas is nitrogen.

[0057] The freeze-drying temperature is -15℃ and the freezing time is 30 minutes.

[0058] In step S3, the fine filtration uses 0.24 m filter element.

[0059] In step S3, the sterilization conditions are: sterilization temperature of 121°C and sterilization time of 30 minutes.

[0060] Comparative Example 1 Unlike Example 1, coconut shell activated carbon was used for filtration.

[0061] Comparative Example 2 Unlike Example 1, no β-cyclodextrin was added to the modified activated carbon; otherwise, it was the same as Example 1.

[0062] Performance tests were conducted on the above embodiments and comparative examples, and the test results are shown in Table 1.

[0063] Test method: Low-temperature stability test method: Ciprofloxacin lactate injection (10ml: 6.38g ciprofloxacin), control sample, and test sample (prepared in the example) were placed in environments of 2±2℃ (refrigerator) and 50±5℃ (constant temperature chamber), respectively, and samples were taken at 30, 60, and 120 days to check the sample properties and clarity. The test results are shown in Table 1.

[0064] Table 1. Performance test results of the examples and comparative examples.

[0065] As can be seen from the table above, the stability of the injection solution in the embodiment is better than that in the comparative example. The main reason may be that the material surface obtained by using freeze-dried chitosan during coarse filtration and high-temperature carbonization contains a large number of amino groups, which can complex metal ions that may be mixed in the injection solution. At the same time, combined with β-cyclodextrin, it has stable solubilization at different temperatures, which greatly improves the stability of the injection solution at low and high temperatures.

[0066] The embodiments described above are merely preferred embodiments of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various other corresponding changes and modifications based on the technical solutions and concepts described above, and all such changes and modifications should fall within the protection scope of the claims of the present invention.

Claims

1. A method for preparing ciprofloxacin lactate injection, characterized in that, Includes the following steps: S1: Weigh 70-80% of the total volume of water for injection, then add sodium sulfite, sodium chloride, and ciprofloxacin lactate in sequence, and stir until completely dissolved; adjust the pH to 3.8-4.0 with lactic acid to obtain the concentrated solution; S2: The concentrated solution is coarsely filtered to obtain the filtrate; S3: Add water for injection to the filtrate to the specified volume, add lactic acid to adjust the pH, stir evenly, filter finely, sterilize, and obtain the product.

2. The method for preparing ciprofloxacin lactate injection according to claim 1, characterized in that, In step S2, modified activated carbon is used for adsorption during coarse filtration, followed by filtration. The modified activated carbon is prepared as follows: Chitosan was dissolved in water to obtain a chitosan suspension. The suspension was stirred, and then acetic acid and β-cyclodextrin were added and mixed to obtain a chitosan aqueous solution. The chitosan aqueous solution was then freeze-dried, removed, carbonized under an inert gas, and cooled to obtain the final product.

3. The method for preparing ciprofloxacin lactate injection according to claim 2, characterized in that, The carbonization temperature is 800-1000℃, and the carbonization time is 60-100min.

4. The method for preparing ciprofloxacin lactate injection according to claim 2, characterized in that, The mass concentration of the acetic acid is 0.01-0.03 mol / L.

5. The method for preparing ciprofloxacin lactate injection according to claim 2, characterized in that, The inert gas is nitrogen.

6. The method for preparing ciprofloxacin lactate injection according to claim 2, characterized in that, The freeze-drying temperature is -5℃ to -20℃, and the freezing time is 20-60 minutes.

7. The method for preparing ciprofloxacin lactate injection according to claim 1, characterized in that, In step S3, the fine filtration uses a pH of 0.20-0.

24. m filter element.

8. The method for preparing ciprofloxacin lactate injection according to claim 1, characterized in that, In step S3, the sterilization conditions are: sterilization temperature of 121°C and sterilization time of 30 minutes.

9. A ciprofloxacin lactate injection, characterized in that, It is prepared by any one of the preparation methods described in claims 1-8.

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