Danofloxacin mesylate microsphere formulation for livestock and poultry and preparation method thereof

Abstract

The invention relates to a danofloxacin mesylate microsphere preparation, which is prepared by the following steps: adding gelatin, or gelatin and polyglycol, or gelatin and polyglycol as well as xanthan gum into water, and adding danofloxacin mesylate for dissolution to obtain a water phase; adding an emulsifying agent into liquid petrolatum to mix evenly to obtain an oil phase; and adding the water phase into the oil phase, emulsifying, cross linking and solidifying the mixed phases and removing supernatant to obtain the danofloxacin mesylate microsphere preparation for livestock and birds.The preparation adopts an emulsifying and condensing method to wrap the danofloxacin mesylate in microspheres, can release slowly after using the microspheres for intramuscular injection, and prolongelimination half-life of medicament in vivo. The preparation technology has the advantages of simple operation, low requirements on preparation equipment and conditions, round shape of the obtained microspheres, and good dispersing property in water solution; and can prolong effective acting time of the medicament in vivo after intramuscular injection for pigs.

Description

technical field

[0001] The invention belongs to the field of animal medicines, and in particular relates to a microsphere preparation of dafloxacin mesylate, a special fluoroquinolone antibacterial drug for animals, and a preparation method thereof. Background technique

[0002] Dafloxacin mesylate is the mesylate of dafloxacin. Dafloxacin is a third-generation fluoroquinolone antibacterial drug for animals. It has broad-spectrum bactericidal effect and is effective against Gram-positive and Gram-negative , Mycoplasma, and Chlamydia all have killing effects. Clinically, it is mainly used for various infections caused by various animal sensitive bacteria.

[0003] Dafloxacin preparations currently on the market are only soluble powders for oral administration and common injections for intramuscular injection. However, due to the short elimination half-life of danofloxacin in animals, it brings inconvenience to clinical application. Therefore, the present invention provides...

Examples

Embodiment 1

[0028] (1) Weigh 1.2g of gelatin in 8ml of water, put it in a constant temperature water bath at 60°C, until the gelatin is completely swollen, add 0.15g of dafloxacin mesylate to it, and make it completely dissolve in the gelatin aqueous solution;

[0029] (2) Add 60ml of liquid paraffin and 1.8ml of Span 80 into a 250ml round bottom flask, stir to make it evenly mixed;

[0030] (3) Slowly add the dafloxacin mesylate gelatin aqueous solution dropwise (0.8ml / min) into the liquid paraffin containing emulsifier in a constant temperature water bath at 60°C, stir magnetically at a stirring speed of 800r / min, and emulsify for 15min , to form an emulsion, and quickly transfer the emulsion to an ice-water bath to lower the temperature below 5°C;

[0031] (4) Continue to stir, add 60ml of isopropanol dropwise therein, continue to stir and continue to stir for 1h. Then add dropwise 4ml of chemical cross-linking agent formaldehyde, the dropping rate is about 1.5ml per minute, continue ...

Embodiment 2

[0035] (1) Precisely weigh 0.8g of gelatin in 8ml of water, put it in a constant temperature water bath at 60°C, until the gelatin is completely swollen, add 0.4g of dafloxacin mesylate to it, and make it completely dissolve in the gelatin aqueous solution;

[0036] (2) Add 60ml of liquid paraffin and 1.8ml of Span 80 into a 250ml round bottom flask, stir to make it evenly mixed;

[0037] (3) Slowly add the dafloxacin mesylate gelatin aqueous solution dropwise (2ml / min) into the liquid paraffin containing emulsifier under the condition of 60°C constant temperature water bath, stir magnetically, the stirring speed is 900r / min, and emulsify for 15min, To form an emulsion, quickly transfer the emulsion to an ice-water bath to lower the temperature below 5°C;

[0038] (4) Continue to stir, add 60ml of isopropanol dropwise therein, continue to stir and continue to stir for 1h. Add 5ml of the chemical cross-linking agent dextran (dextran) dropwise therein, at a rate of about 0.5ml ...

Embodiment 3

[0042] (1) Accurately weigh 1.2g of gelatin and 0.24g of polyethylene glycol in 8ml of water, place in a constant temperature water bath at 60°C, until the gelatin is completely swollen, add 0.30g of dafloxacin mesylate to it, and dissolve it completely;

[0043] (2) Add 60ml of liquid paraffin and 1.5ml of Span 80 into a 250ml round bottom flask, stir to make it evenly mixed;

[0044] (3) Slowly add the dafloxacin mesylate gelatin aqueous solution dropwise (1.5ml / min) into the liquid paraffin containing surfactant under the condition of constant temperature water bath at 60°C, stir magnetically, the stirring speed is 1000r / min, and emulsify After 15 minutes, an emulsion is formed, and the emulsion is quickly transferred to an ice-water bath to lower the temperature below 5°C;

[0045] (4) Continue to stir, add 60ml of isopropanol dropwise therein, continue to stir and continue to stir for 1h. Then dropwise add 5ml of chemical cross-linking agent glutaraldehyde, the rate of a...

technical field

[0001] The invention belongs to the field of animal medicines, and in particular relates to a microsphere preparation of dafloxacin mesylate, a special fluoroquinolone antibacterial drug for animals, and a preparation method thereof. Background technique

[0002] Dafloxacin mesylate is the mesylate of dafloxacin. Dafloxacin is a third-generation fluoroquinolone antibacterial drug for animals. It has broad-spectrum bactericidal effect and is effective against Gram-positive and Gram-negative , Mycoplasma, and Chlamydia all have killing effects. Clinically, it is mainly used for various infections caused by various animal sensitive bacteria.

[0003] Dafloxacin preparations currently on the market are only soluble powders for oral administration and common injections for intramuscular injection. However, due to the short elimination half-life of danofloxacin in animals, it brings inconvenience to clinical application. Therefore, the present invention provides...

Examples

Embodiment 1

[0028] (1) Weigh 1.2g of gelatin in 8ml of water, put it in a constant temperature water bath at 60°C, until the gelatin is completely swollen, add 0.15g of dafloxacin mesylate to it, and make it completely dissolve in the gelatin aqueous solution;

[0029] (2) Add 60ml of liquid paraffin and 1.8ml of Span 80 into a 250ml round bottom flask, stir to make it evenly mixed;

[0030] (3) Slowly add the dafloxacin mesylate gelatin aqueous solution dropwise (0.8ml / min) into the liquid paraffin containing emulsifier in a constant temperature water bath at 60°C, stir magnetically at a stirring speed of 800r / min, and emulsify for 15min , to form an emulsion, and quickly transfer the emulsion to an ice-water bath to lower the temperature below 5°C;

[0031] (4) Continue to stir, add 60ml of isopropanol dropwise therein, continue to stir and continue to stir for 1h. Then add dropwise 4ml of chemical cross-linking agent formaldehyde, the dropping rate is about 1.5ml per minute, continue ...

Embodiment 2

[0035] (1) Precisely weigh 0.8g of gelatin in 8ml of water, put it in a constant temperature water bath at 60°C, until the gelatin is completely swollen, add 0.4g of dafloxacin mesylate to it, and make it completely dissolve in the gelatin aqueous solution;

[0036] (2) Add 60ml of liquid paraffin and 1.8ml of Span 80 into a 250ml round bottom flask, stir to make it evenly mixed;

[0037] (3) Slowly add the dafloxacin mesylate gelatin aqueous solution dropwise (2ml / min) into the liquid paraffin containing emulsifier under the condition of 60°C constant temperature water bath, stir magnetically, the stirring speed is 900r / min, and emulsify for 15min, To form an emulsion, quickly transfer the emulsion to an ice-water bath to lower the temperature below 5°C;

[0038] (4) Continue to stir, add 60ml of isopropanol dropwise therein, continue to stir and continue to stir for 1h. Add 5ml of the chemical cross-linking agent dextran (dextran) dropwise therein, at a rate of about 0.5ml ...

Embodiment 3

[0042] (1) Accurately weigh 1.2g of gelatin and 0.24g of polyethylene glycol in 8ml of water, place in a constant temperature water bath at 60°C, until the gelatin is completely swollen, add 0.30g of dafloxacin mesylate to it, and dissolve it completely;

[0043] (2) Add 60ml of liquid paraffin and 1.5ml of Span 80 into a 250ml round bottom flask, stir to make it evenly mixed;

[0044] (3) Slowly add the dafloxacin mesylate gelatin aqueous solution dropwise (1.5ml / min) into the liquid paraffin containing surfactant under the condition of constant temperature water bath at 60°C, stir magnetically, the stirring speed is 1000r / min, and emulsify After 15 minutes, an emulsion is formed, and the emulsion is quickly transferred to an ice-water bath to lower the temperature below 5°C;

[0045] (4) Continue to stir, add 60ml of isopropanol dropwise therein, continue to stir and continue to stir for 1h. Then dropwise add 5ml of chemical cross-linking agent glutaraldehyde, the rate of a...

Images