Preparation method of tilmicosin liposomes

Abstract

The invention relates to a preparation method of tilmicosin liposomes. In the technical scheme, every 3g of tilmicosin raw powder is processed into tilmicosin liposomes by the following steps: (1) preparing a PBS buffer solution with the pH value of 6.5 to 7.5; (2) mixing egg yolk lecithin, cholesterol, octadecylamine, polysorbate-80 and ether in the proportion into a solution; (3) mixing the tilmicosin raw powder with the PBS buffer solution obtained in the step (1), and then pouring the mixture into the solution prepared in the step (2) and uniformly stirring; pulverizing the mixture by ultrasound into a suspension which does not delaminate within at least 5min; (4) transferring the suspension in the step (3) into a rotary evaporator to perform pressure-reduction rotary evaporation so that the suspension is condensed on the wall of the rotary evaporator to form lipid membranes; and (5) washing off the lipid membranes completely with the PBS solution obtained in the step (1), and thencontinuing the pressure-reduction evaporation until the ether is drained entirely to obtain tilmicosin liposome crude products. The method has the advantages of simple steps and strong operability. The prepared tilmicosin liposomes can be easily absorbed after being injected into livestock and poultry organisms; and the phenomenon of local swelling can not be caused.

Description

technical field

[0001] The invention belongs to the field of antibiotic preparations, and in particular relates to a preparation method of tilmicosin liposome dosage form. Background technique

[0002] Tilmicosin is a semi-synthetic macrolide antibiotic for livestock and poultry developed by the British Elanco company in the 1980s. It has been approved abroad for the treatment of infectious diseases in pigs, cattle, sheep, chickens and other animals. Diseases, especially livestock and poultry respiratory infections, such as livestock actinobacillus pleuropneumonia, pasteurellosis and chicken mycoplasma, etc., are effective to gram-positive bacteria, some gram-negative bacteria, mycoplasma and spirochetes inhibition. Compared with tylosin, tilmicosin has stronger antibacterial activity, less dosage (it is reported that the dosage of subcutaneous or intravenous injection is 10-20 mg / Kg body weight, once effective), long-lasting effect and other advantages. It is an economical...

Examples

Embodiment 1

[0024] The preparation method of tilmicosin liposome comprises the following steps:

[0025] 1) Prepare PBS buffer solution with pH 7.0.

[0026] 2) Take 1.5g of egg yolk lecithin, 0.35g of cholesterol, 0.08g of octadecylamine, 0.5ml of Tween-80, and 45ml of ether, mix them, and heat them in a water bath to 60°C to promote the dissolution of the raw materials into a solution.

[0027] 3) Take 3g of tilmicosin powder and 50ml of the PBS buffer solution in step 1), mix them and pour them into the solution prepared in step 2) and stir evenly. Put the uniformly stirred mixture in a cell lyser for ultrasonic pulverization treatment, the ultrasonic frequency is 60HZ, and the intermittent working mode is implemented with a working time of 2s and an interval time of 3s. The processing temperature is 35°C, and the total processing time is 17min. The solution dispersed into a non-layered suspension for at least 5 minutes.

[0028] 4) Transfer the suspension in step 3) to a rotary evap...

Embodiment 2

[0039] The preparation method of tilmicosin liposome comprises the following steps:

[0040] 1) Prepare a PBS buffer solution with a pH of 6.5.

[0041] 2) Mix 1g of egg yolk lecithin, 0.3g of cholesterol, 0.05g of octadecylamine, 0.3ml of Tween-80, and 42ml of ether, and heat it in a water bath to 55°C to promote the dissolution of the raw materials into a solution.

[0042] 3) Take 3g of tilmicosin powder and 48ml of the PBS buffer solution in step 1), mix them and pour them into the solution prepared in step 2) and stir evenly. Put the uniformly stirred mixture in a cell lyser for ultrasonic pulverization treatment, the ultrasonic frequency is 60HZ, and the intermittent working mode is implemented with a working time of 2s and an interval time of 3s. The processing temperature is 35°C, and the total processing time is 17min. The solution dispersed into a non-layered suspension for at least 5 minutes.

[0043]4) Transfer the suspension in step 3) to a rotary evaporator for...

Embodiment 3

[0050] The preparation method of tilmicosin liposome comprises the following steps:

[0051] 1) Prepare a PBS buffer solution with a pH of 7.5.

[0052] 2) Mix 2g of egg yolk lecithin, 0.4g of cholesterol, 0.1g of octadecylamine, 0.7ml of Tween-80, and 48ml of diethyl ether, and heat it in a water bath to 75°C to promote the dissolution of the raw materials into a solution.

[0053] 3) Take 3g of tilmicosin powder and 52ml of the PBS buffer solution in step 1), mix them and pour them into the solution prepared in step 2) and stir evenly. Put the uniformly stirred mixture in a cell lyser for ultrasonic pulverization treatment, the ultrasonic frequency is 60HZ, and the intermittent working mode is implemented with a working time of 2s and an interval time of 3s. The processing temperature is 35°C, and the total processing time is 17min. The solution dispersed into a non-layered suspension for at least 5 minutes.

[0054] 4) Transfer the suspension in step 3) to a rotary evapor...

technical field

[0001] The invention belongs to the field of antibiotic preparations, and in particular relates to a preparation method of tilmicosin liposome dosage form. Background technique

[0002] Tilmicosin is a semi-synthetic macrolide antibiotic for livestock and poultry developed by the British Elanco company in the 1980s. It has been approved abroad for the treatment of infectious diseases in pigs, cattle, sheep, chickens and other animals. Diseases, especially livestock and poultry respiratory infections, such as livestock actinobacillus pleuropneumonia, pasteurellosis and chicken mycoplasma, etc., are effective to gram-positive bacteria, some gram-negative bacteria, mycoplasma and spirochetes inhibition. Compared with tylosin, tilmicosin has stronger antibacterial activity, less dosage (it is reported that the dosage of subcutaneous or intravenous injection is 10-20 mg / Kg body weight, once effective), long-lasting effect and other advantages. It is an economical...

Examples

Embodiment 1

[0024] The preparation method of tilmicosin liposome comprises the following steps:

[0025] 1) Prepare PBS buffer solution with pH 7.0.

[0026] 2) Take 1.5g of egg yolk lecithin, 0.35g of cholesterol, 0.08g of octadecylamine, 0.5ml of Tween-80, and 45ml of ether, mix them, and heat them in a water bath to 60°C to promote the dissolution of the raw materials into a solution.

[0027] 3) Take 3g of tilmicosin powder and 50ml of the PBS buffer solution in step 1), mix them and pour them into the solution prepared in step 2) and stir evenly. Put the uniformly stirred mixture in a cell lyser for ultrasonic pulverization treatment, the ultrasonic frequency is 60HZ, and the intermittent working mode is implemented with a working time of 2s and an interval time of 3s. The processing temperature is 35°C, and the total processing time is 17min. The solution dispersed into a non-layered suspension for at least 5 minutes.

[0028] 4) Transfer the suspension in step 3) to a rotary evap...

Embodiment 2

[0039] The preparation method of tilmicosin liposome comprises the following steps:

[0040] 1) Prepare a PBS buffer solution with a pH of 6.5.

[0041] 2) Mix 1g of egg yolk lecithin, 0.3g of cholesterol, 0.05g of octadecylamine, 0.3ml of Tween-80, and 42ml of ether, and heat it in a water bath to 55°C to promote the dissolution of the raw materials into a solution.

[0042] 3) Take 3g of tilmicosin powder and 48ml of the PBS buffer solution in step 1), mix them and pour them into the solution prepared in step 2) and stir evenly. Put the uniformly stirred mixture in a cell lyser for ultrasonic pulverization treatment, the ultrasonic frequency is 60HZ, and the intermittent working mode is implemented with a working time of 2s and an interval time of 3s. The processing temperature is 35°C, and the total processing time is 17min. The solution dispersed into a non-layered suspension for at least 5 minutes.

[0043]4) Transfer the suspension in step 3) to a rotary evaporator for...

Embodiment 3

[0050] The preparation method of tilmicosin liposome comprises the following steps:

[0051] 1) Prepare a PBS buffer solution with a pH of 7.5.

[0052] 2) Mix 2g of egg yolk lecithin, 0.4g of cholesterol, 0.1g of octadecylamine, 0.7ml of Tween-80, and 48ml of diethyl ether, and heat it in a water bath to 75°C to promote the dissolution of the raw materials into a solution.

[0053] 3) Take 3g of tilmicosin powder and 52ml of the PBS buffer solution in step 1), mix them and pour them into the solution prepared in step 2) and stir evenly. Put the uniformly stirred mixture in a cell lyser for ultrasonic pulverization treatment, the ultrasonic frequency is 60HZ, and the intermittent working mode is implemented with a working time of 2s and an interval time of 3s. The processing temperature is 35°C, and the total processing time is 17min. The solution dispersed into a non-layered suspension for at least 5 minutes.

[0054] 4) Transfer the suspension in step 3) to a rotary evapor...