Compound long-acting injection containing enrofloxacin and meloxicam, and preparation method of compound long-acting injection

Abstract

The present invention discloses a compound long-acting injection containing enrofloxacin and meloxicam. The compound long-acting injection comprises the enrofloxacin and / or a salt thereof, the meloxicam in a dispersion form, a meloxicam solid dispersoid, a high molecular retardant, a wetting agent and a dispersion medium; each 1,000 mL of the injection contains 20-250 g of the enrofloxacin and / orthe salt thereof (calculated by the enrofloxacin), 5-50 g of the meloxicam in the dispersion form, 5-30 g of the high molecular retardant, 5-20 g of the wetting agent, and the balance of a dispersionmedium; and a mass ratio of the meloxicam in the dispersion form to the meloxicam solid dispersoid (calculated by the meloxicam) is (5:1)-(1:1). The injection preparation is stable in quality, slow indrug release, safe and effective, only 1-2 times of drug administration in one course of treatment can treat both symptoms and root causes, and effective blood drug concentration is maintained for 3-7 days; and only 1 needle is used for injection for 1 time, so that the compound long-acting injection enhances animal compliance, reduces animal stress and is more favorable for disease outcome and prognosis.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations for animals, and relates to a compound long-acting injection containing enrofloxacin and meloxicam and a preparation method thereof. Background technique

[0002] Enrofloxacin is also known as ethyl ciprofloxacin and enrofloxacin. It has a wide antibacterial spectrum and strong bactericidal power. It has a strong effect on Gram-positive bacteria, negative bacteria, mycoplasma, and some anaerobic bacteria, especially on Gram-negative bacilli. Sensitive bacteria include Staphylococcus aureus Coccus, Streptococcus, Actinomyces pyogenes, Escherichia coli, Salmonella, Pasteurella, Klebsiella, Proteus, Pseudomonas aeruginosa, Haemophilus, Bordetella, Erysipelas; have special effects on mycoplasma, It is more effective than tylosin and colistin, and it is still effective against both drug-resistant mycoplasma, especially against mycoplasma gallisepticum; it also has a certain effect on mycobac...

Examples

specific Embodiment approach

[0034] Enrofloxacin or its salts shall be ultrafinely pulverized, and the particle size D90 shall be ≤5 μm, and no particles above 25 μm shall be detected.

[0035] Meloxicam is ultrafinely pulverized to control the particle size D90≤5μm, and no particles above 25μm can be detected.

[0036] The ultrafine pulverization process is as follows:

[0037] The fluidized bed supersonic airflow superfine pulverization and classification system is adopted, and the material input volume is controlled at 60-80g. The materials collide with each other at the speed of Mach 2.5 in the crushing chamber, and are crushed quickly. The crushed particles rise to the classification chamber with the airflow, and the qualified particles enter the cyclone separator with the airflow, and finally obtain the desired product, and the tail gas enters the dust collector to be discharged. Under the action of the classifier, the larger particles fall back to the crushing chamber and are crushed again until ...

Embodiment 1

[0039] prescription

[0040]

[0041] Among them, the meloxicam solid dispersion is prepared by the following method: add 100.0g meloxicam to 100.0g dimethylformamide, mix well, and sonicate for 1h; In the molten mixture of 50.0g Poloxamer 188 and 250.0g polyethylene glycol 6000, stir for 0.5h; pour the molten material onto a frozen stainless steel plate, after cooling and solidifying, pulverize and sieve to obtain meloxicam solid Dispersion, spare.

[0042] The preparation method of the long-acting injection containing enrofloxacin and meloxicam:

[0043] Take an appropriate amount of isopropyl myristate, heat it to 150-180°C, and continue for 1 hour; take 700mL of heat-treated isopropyl myristate, cool it down to 120-140°C, add aluminum monostearate, hydrogenated castor oil , maintain 1-2h, make aluminum monostearate, hydrogenated castor oil gel completely; let cool to 40-60 ℃, add white wax, Span 60, lecithin, enrofloxacin, meloxicam solid dispersion and meloxicam in ...

Embodiment 2

[0050] prescription

[0051]

[0052] Among them, the meloxicam solid dispersion is prepared by the following method: add 100.0g meloxicam to 100.0g dimethylformamide, mix well, and sonicate for 1h; Melt 100.0g of poloxamer 188 and 200.0g of polyethylene glycol 12000 mixture, stir for 1h; pour the molten material onto a frozen stainless steel plate, cool and solidify, pulverize and sieve to obtain meloxicam solid dispersion Body, spare.

[0053] The preparation method of the long-acting injection containing enrofloxacin and meloxicam: take an appropriate amount of soybean oil, heat it to 150-180°C for 1 hour; take 700mL of heat-treated soybean oil, cool it to 120-140°C, Add aluminum monostearate and hydrogenated castor oil and keep for 1-2 hours to completely gel the aluminum monostearate and hydrogenated castor oil; let it cool to 40-60°C, add polyvinyl alcohol, Tween 80, polylauric acid Oxyethylene glyceride, hydroxylated lecithin, enrofloxacin sodium, enrofloxacin lact...

technical field

[0001] The invention belongs to the field of pharmaceutical preparations for animals, and relates to a compound long-acting injection containing enrofloxacin and meloxicam and a preparation method thereof. Background technique

[0002] Enrofloxacin is also known as ethyl ciprofloxacin and enrofloxacin. It has a wide antibacterial spectrum and strong bactericidal power. It has a strong effect on Gram-positive bacteria, negative bacteria, mycoplasma, and some anaerobic bacteria, especially on Gram-negative bacilli. Sensitive bacteria include Staphylococcus aureus Coccus, Streptococcus, Actinomyces pyogenes, Escherichia coli, Salmonella, Pasteurella, Klebsiella, Proteus, Pseudomonas aeruginosa, Haemophilus, Bordetella, Erysipelas; have special effects on mycoplasma, It is more effective than tylosin and colistin, and it is still effective against both drug-resistant mycoplasma, especially against mycoplasma gallisepticum; it also has a certain effect on mycobac...

Examples

specific Embodiment approach

[0034] Enrofloxacin or its salts shall be ultrafinely pulverized, and the particle size D90 shall be ≤5 μm, and no particles above 25 μm shall be detected.

[0035] Meloxicam is ultrafinely pulverized to control the particle size D90≤5μm, and no particles above 25μm can be detected.

[0036] The ultrafine pulverization process is as follows:

[0037] The fluidized bed supersonic airflow superfine pulverization and classification system is adopted, and the material input volume is controlled at 60-80g. The materials collide with each other at the speed of Mach 2.5 in the crushing chamber, and are crushed quickly. The crushed particles rise to the classification chamber with the airflow, and the qualified particles enter the cyclone separator with the airflow, and finally obtain the desired product, and the tail gas enters the dust collector to be discharged. Under the action of the classifier, the larger particles fall back to the crushing chamber and are crushed again until ...

Embodiment 1

[0039] prescription

[0040]

[0041] Among them, the meloxicam solid dispersion is prepared by the following method: add 100.0g meloxicam to 100.0g dimethylformamide, mix well, and sonicate for 1h; In the molten mixture of 50.0g Poloxamer 188 and 250.0g polyethylene glycol 6000, stir for 0.5h; pour the molten material onto a frozen stainless steel plate, after cooling and solidifying, pulverize and sieve to obtain meloxicam solid Dispersion, spare.

[0042] The preparation method of the long-acting injection containing enrofloxacin and meloxicam:

[0043] Take an appropriate amount of isopropyl myristate, heat it to 150-180°C, and continue for 1 hour; take 700mL of heat-treated isopropyl myristate, cool it down to 120-140°C, add aluminum monostearate, hydrogenated castor oil , maintain 1-2h, make aluminum monostearate, hydrogenated castor oil gel completely; let cool to 40-60 ℃, add white wax, Span 60, lecithin, enrofloxacin, meloxicam solid dispersion and meloxicam in ...

Embodiment 2

[0050] prescription

[0051]

[0052] Among them, the meloxicam solid dispersion is prepared by the following method: add 100.0g meloxicam to 100.0g dimethylformamide, mix well, and sonicate for 1h; Melt 100.0g of poloxamer 188 and 200.0g of polyethylene glycol 12000 mixture, stir for 1h; pour the molten material onto a frozen stainless steel plate, cool and solidify, pulverize and sieve to obtain meloxicam solid dispersion Body, spare.

[0053] The preparation method of the long-acting injection containing enrofloxacin and meloxicam: take an appropriate amount of soybean oil, heat it to 150-180°C for 1 hour; take 700mL of heat-treated soybean oil, cool it to 120-140°C, Add aluminum monostearate and hydrogenated castor oil and keep for 1-2 hours to completely gel the aluminum monostearate and hydrogenated castor oil; let it cool to 40-60°C, add polyvinyl alcohol, Tween 80, polylauric acid Oxyethylene glyceride, hydroxylated lecithin, enrofloxacin sodium, enrofloxacin lact...

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