Tilmicosin micelle preparation and preparation method thereof

Abstract

The invention belongs to the technical field of medicinal preparations and relates to a tilmicosin micelle preparation and a preparation method thereof. The tilmicosin micelle preparation comprises the following components in part by weight: 3 to 5 parts of tilmicosin, 5.0 to 15.5 parts of pharmaceutically acceptable carrier materials, 52 to 68 parts of poly(butylene succinate) (PBS ), 0 to 8 parts of additive and a pH modifier, wherein the pH value of the pH modifier is 5 to 7. In the tilmicosin micelle preparation, poloxamer 188 serves as the main micelle component. The poloxamer 188 is an asymmetric amphiphilic block copolymer and can automatically form the micelle in aqueous solution, wherein the hydrophobic block of the micelle gathers inwards and the hydrophilic block gathers outwards. Because the formed micelle is relatively smaller low in particle size, the micelle is higher in retention capability to an inflammatory part and stable onto heat and is not easy to oxidize. The entrapment rate and the drug loading capacity of the tilmicosin micelle preparation are high.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and relates to a tilmicosin micellar preparation and a preparation method thereof. Background technique [0002] Tilmicosin (Tilmicosin) is a kind of animal-specific macrolide antibiotic developed by Elanco in the 1980s, and was approved for marketing in my country in the 1990s. It is white or light yellow crystalline powder, easily soluble in methanol, acetonitrile, acetone, soluble in ethanol, almost insoluble in n-hexane. [0003] Tilmicosin has special antibacterial activity and pharmacological characteristics, and has inhibitory effects on Gram-positive bacteria and some Gram-negative bacteria, mycoplasma, spirochetes, etc., especially against Actinomyces pleuropneumoniae, hemolytic Pasteurella Bacillus, Pasteurella multocida and Mycoplasma poultry have lighter antibacterial activity than tylosin; its pharmacokinetics have been studied in cows, dairy goats, sheep, pigs, ...

AI Technical Summary

Problems solved by technology

[0005] Like most traditional preparations, tilmicosin drinking water, tablets, and ordinary injections are released according to first-order kinetics, and the drug concentration in the blood fluctuates greatly, often showing "peaks and valleys". The toxic concentration is at the bottom, and the effective blood concentration is maintained for a short time. It often requires repeated administration to achieve effective treatment, reduce side effects, and increase costs. In addition, repeated administration of some dosage forms is more irritating to animals, and the stress response is obvious. Not conducive to the healthy growth of animals

[0006] Safety issues of tilmicosin injection, such as subcutaneous injection of cows, 50mg per 1kg body weight can cause myocardial toxicity, 150mg can be fatal; intramuscular injection of pigs, 10mg per 1kg body weight can cause rapid breathing, vomiting and convulsions, 20mg can cause large Some test pigs died, which limited the application of tilmicosin injection. At present, most veterinary drug companies have developed nanoemulsion and liposome preparations of tilmicosin to solve the safety problem of the injection, but the liposome Phospholipids, cholesterol, etc. are commonly used in the preparation. These auxiliary materials have the disadvantages of heat resistance and easy oxidation and deterioration, so it is difficult to store them for a long time.

And patent CN101422435A, the prepared liposome preparation has been carried out freeze-drying process, although solved the shortcoming of liposome preparation instability, but increased the cost of industrialization, it is difficult to popularize in the veterinary market