Quinolone veterinary lipid sustained-release granules and a method for preparing the same

Abstract

The application discloses a quinolone lipid slow-release granule for animals and a preparation method thereof, and relates to the field of animal medicines, which is composed of the following components in mass parts: 8-50% of quinolone main medicine, 45-90% of lipid matrix, 0-2% of antioxidant, 0-2% of light shielding agent and 0-0.5% of food attractant. Compared with the prior art, the application has the beneficial effects that: 1. the medicine is uniformly dispersed in the lipid matrix, the taste is fully covered, and the pig has high palatability; 2. the production process is less, and only melting, granulation and cooling are needed to complete, so that the equipment and production cost are lower; 3. the melting temperature is low, the quinolone medicine is not easy to decompose, and the product has good stability; 4. the particle size is moderate, the granule can be uniformly mixed with feed, and is suitable for batch feeding in a farm; 5. the medicine is slow-released, has a long action time, and has good treatment effect on pig bacterial respiratory tract infection; and 6. the application can be adapted to various quinolone medicines, and is suitable for pigs, cattle, sheep, dogs, cats and other animals.

Description

Technical Field

[0001] This invention relates to the field of veterinary drugs, specifically a quinolone-based veterinary lipid sustained-release granule and its preparation method. Background Technology

[0002] Quinolone veterinary drugs include enrofloxacin, marbofloxacin, dalofaxin, sarafloxacin, diflufloxacin, and their pharmaceutical salts. They have a broad antibacterial spectrum and are commonly used for the prevention and treatment of bacterial respiratory infections in livestock and poultry. However, the drugs themselves have a strong bitter taste. Currently available oral dosage forms are mainly soluble powders, solutions, and tablets. Soluble powders and solutions are suitable for poultry with low taste sensitivity, while pigs, cattle, sheep, and other livestock have sensitive taste buds and are prone to refusing to eat. Tablets cannot be mixed with feed for group administration, making them inconvenient for large-scale farming.

[0003] Currently, enrofloxacin granules using wet granulation and film coating processes are available on the market. While these processes can mask the bitterness to some extent, they have significant drawbacks: First, the process is cumbersome, requiring multiple steps such as wet mixing, soft material preparation, spheroidization, drying, granulation, and coating. This results in numerous supporting equipment, a long production cycle, and high overall costs. Second, the granulation process generates fine powder that cannot be completely coated, leaving the bitter taste of the drug exposed. Some sensitive pigs still refuse to eat it, and the masking effect is unstable. Summary of the Invention

[0004] The purpose of this invention is to provide a quinolone-based veterinary lipid sustained-release granule and its preparation method, so as to solve the problems mentioned in the background art.

[0005] To achieve the above objectives, the present invention provides the following technical solution: A quinolone-based veterinary lipid sustained-release granule, by weight, is composed of the following raw materials: 8%-50% quinolone active ingredient, 45%-90% lipid matrix, 0%-2% antioxidant, 0%-2% light-blocking agent, and 0%-0.5% palatability enhancer.

[0006] As a further aspect of the present invention: the quinolone active ingredient comprises 10%-30%, and the quinolone active ingredient is selected from one or more of enrofloxacin, mabofloxacin, daflufloxacin, sarafloxacin, diflufloxacin and their pharmaceutical salts.

[0007] As a further embodiment of the present invention, the lipid matrix is ​​selected from at least one of glyceryl monostearate, glyceryl distearate, and a mixture of glyceryl monostearate and glyceryl distearate.

[0008] As a further embodiment of the present invention, the antioxidant is selected from one or more of BHT, BHA, propyl gallate, vitamin E (d-α-tocopherol, tocopheryl acetate), and ascorbyl palmitate.

[0009] As a further embodiment of the present invention: the light-blocking agent is selected from one or more of titanium dioxide, talc, calcium carbonate, and iron oxide (red, yellow, and black).

[0010] As a further aspect of the present invention: the palatability enhancer is selected from one or more of suckling pig flavor, edible flavoring, and sodium saccharin.

[0011] A method for preparing a quinolone-based veterinary lipid sustained-release granule, used to prepare any of the granules described above, the method comprising the following steps: (1) Molten lipid matrix: Take the lipid matrix and heat it in a water bath or oil bath to melt it. The melting temperature is 40-120℃. (2) Mixing the materials: Add quinolone active pharmaceutical ingredient, antioxidant, light-blocking agent and palatability enhancer to the molten lipid matrix, and stir for 10-15 minutes until the system is homogeneous; (3) Melt molding granulation: Select either extrusion granulation or rotary centrifugal granulation to granulate the melt mixture; (4) Cooling and shaping with cold air: The molded granules are cooled with cold air to below 50°C to obtain lipid sustained-release granules.

[0012] As a further aspect of the present invention: step (1) uses oil bath heating, and the melting temperature is controlled at 60-80℃.

[0013] As a further embodiment of the present invention: in step (3), the screen mesh size is 16-100 mesh, the extrusion temperature is kept at 50-55℃, and the cold air cools the particles to below 40℃.

[0014] As a further embodiment of the present invention: the rotary centrifugal pelletizing operation: the molten material is fed into a rotary pelletizer equipped with 40-60 mesh fine holes, the rotation speed is controlled at 200-500 rpm, and the material is ejected and solidified into shape upon contact with cold air.

[0015] Compared with the prior art, the beneficial effects of the present invention are: 1. The drug is evenly dispersed in the lipid matrix, providing sufficient taste masking and resulting in high palatability for pigs; 2. Fewer production steps, only melting, granulation, and cooling are required, resulting in lower equipment and production costs; 3. Low melting temperature, which reduces the likelihood of quinolone drug decomposition and ensures good product stability; 4. The pellet size is moderate, which can be mixed evenly with feed, making it suitable for batch mixing in farms; 5. The drug is released slowly and has a long duration of action, resulting in good therapeutic effects on bacterial respiratory infections in pigs; 6. Compatible with a variety of quinolone drugs, suitable for animals such as pigs, cattle, sheep, dogs, and cats. Attached Figure Description

[0016] Figure 1 This is a process flow diagram for preparing a quinolone-based veterinary lipid sustained-release granule. Detailed Implementation

[0017] The present invention will be further described below with reference to specific embodiments. The following embodiments are only used to explain the present invention and do not constitute a limitation on the scope of protection of the present invention.

[0018] Example 1 The weight ratio is as follows: Enrofloxacin 20%, glyceryl monostearate 50%, glyceryl distearate 29.6%, BHT 0.1%, and titanium dioxide 0.3%.

[0019] Preparation steps: (1) Take glyceryl monostearate and glyceryl distearate and BHT and place them in a preparation tank. Stir in a water bath at 60°C until completely melted. (2) Add enrofloxacin and titanium dioxide to the preparation container and stir for 10 minutes; (3) Run the extrusion granulator, start the external air cooler, add the above medicine liquid into the granulator, keep it at about 55°C and extrude the granules; (4) Maintain the power of the cold air blower to keep the temperature of the cooled particles below 40°C during the granulation process, and package them after inspection and approval.

[0020] Example 2 The formula by weight is as follows: Enrofloxacin 10%, glyceryl mono- and di-stearates 89.6%, and piglet flavoring 0.4%.

[0021] Preparation steps: (1) Take glyceryl monostearate and glyceryl distearate and pig spice and place them in a preparation tank. Stir and melt them completely in an oil bath at 65°C. (2) Add enrofloxacin to the preparation container and stir for 11 minutes; (3) Add the heated and molten medicine liquid into a granulator equipped with a 40-mesh fine hole, control the rotation speed of the granulator rotating head to 200 rpm, and throw out the medicine liquid. The medicine liquid solidifies into granules when it encounters cold air. (4) Maintain the power of the cold air blower to keep the temperature of the cooled particles below 40°C during the granulation process.

[0022] Example 3 The weight ratio is as follows: Marbofloxacin 10%, glyceryl monostearate and glyceryl distearate 89.7%, BHT 0.1%, titanium dioxide 0.2%.

[0023] Preparation steps: (1) Take glyceryl monostearate and glyceryl distearate and BHT and place them in a preparation tank. Stir and melt them completely in a water bath at 75°C. (2) Add mabofloxacin and titanium dioxide to the preparation container and stir for 14 minutes; (3) Run the extrusion granulator, start the external cold air fan, add the above medicine liquid into the granulator, keep it at about 45°C for extrusion granulation; (4) Maintain the power of the cold air blower to keep the temperature of the cooled particles below 40°C during the granulation process, and package them after inspection and approval.

[0024] Example 4 The weight ratio is as follows: Marbofloxacin 20%, glyceryl monostearate and glyceryl distearate 79.6%, BHT 0.2%, titanium dioxide 0.2%.

[0025] Preparation steps: (1) Take glyceryl monostearate and glyceryl distearate and BHT and place them in a preparation tank. Stir and melt them completely in an oil bath at 80°C. (2) Add mabofloxacin and titanium dioxide to the preparation container and stir for 15 minutes; (3) Add the heated and molten medicine liquid into a granulator equipped with a 60-mesh fine hole, control the rotation speed of the granulator head to 500 rpm, and throw out the medicine liquid. The medicine liquid solidifies into granules when it encounters cold air. (4) Maintain the power of the cold air blower to keep the temperature of the cooled particles below 40°C during the granulation process.

[0026] The sample prepared in Example 1 was used to treat respiratory diseases in pigs caused by susceptible bacteria such as Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus.

[0027] Dosage: Mix 0.1%-0.15% into feed. Dosage is calculated as enrofloxacin, single dose: 7.5 mg per kg body weight for pigs. For cases of severe or chronic respiratory disease, a supplemental dose can be given after 48 hours.

[0028] A randomized trial was conducted on 100 pigs, showing a palatability rate of 98%, an improvement rate of 86%, and a cure rate of 73%. Given the domestic market, this product has significant potential value.

[0029] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

[0030] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A quinolone-based veterinary lipid sustained-release granule formulation, characterized in that, By weight, it is composed of the following raw materials: 8%-50% quinolone active ingredient, 45%-90% lipid matrix, 0%-2% antioxidant, 0%-2% light-blocking agent, and 0%-0.5% palatability enhancer.

2. The quinolone-based veterinary lipid sustained-release granule formulation according to claim 1, characterized in that, The quinolone active ingredient comprises 10%-30%, and is selected from one or more of enrofloxacin, mabofloxacin, dafluxacin, sarafloxacin, diflufloxacin, and their pharmaceutical salts.

3. The quinolone-based veterinary lipid sustained-release granule formulation according to claim 1, characterized in that, The lipid matrix is ​​selected from at least one of glyceryl monostearate, glyceryl distearate, and a mixture of glyceryl monostearate and glyceryl distearate.

4. The quinolone-based veterinary lipid sustained-release granule formulation according to claim 1, characterized in that, The antioxidant is selected from one or more of BHT, BHA, propyl gallate, vitamin E, and ascorbyl palmitate.

5. The quinolone-based veterinary lipid sustained-release granule formulation according to claim 1, characterized in that, The light-blocking agent is selected from one or more of titanium dioxide, talc, calcium carbonate, and iron oxide.

6. The quinolone-based veterinary lipid sustained-release granule according to claim 1, characterized in that, The palatability enhancer is selected from one or more of suckling pig flavor, edible flavoring, and sodium saccharin.

7. A method for preparing a quinolone-based veterinary lipid sustained-release granule, used to prepare the granule according to any one of claims 1-6, characterized in that, It includes the following steps: (1) Molten lipid matrix: Take the lipid matrix and heat it in a water bath or oil bath to melt it. The melting temperature is 40-120℃. (2) Mixing the materials: Add quinolone active pharmaceutical ingredient, antioxidant, light-blocking agent and palatability enhancer to the molten lipid matrix, and stir for 10-15 minutes until the system is homogeneous; (3) Melt molding granulation: Select either extrusion granulation or rotary centrifugal granulation to granulate the melt mixture; (4) Cooling and shaping with cold air: The molded granules are cooled with cold air to below 50°C to obtain lipid sustained-release granules.

8. The preparation method according to claim 7, characterized in that, Step (1) uses oil bath heating, and the melting temperature is controlled at 60-80℃.

9. The preparation method according to claim 7, characterized in that, In step (3), the screen mesh size is 16-100 mesh, the extrusion temperature is kept at 50-55℃, and the cold air cools the particles to below 40℃.

10. The preparation method according to claim 7, characterized in that, The rotary centrifugal pelletizing operation: molten material is fed into a rotary pelletizer equipped with 40-60 mesh fine holes, and the rotation speed is controlled at 200-500 rpm. After the material is thrown out, it solidifies and forms a shape when it encounters cold air.

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