KR-20260067737-A - Antibiotics for companion animals comprising amoxicillin with improved pharmacokinetic properties and use thereof

Abstract

The present application relates to a sustained-release antibiotic for companion animals comprising amoxicillin and the use thereof. The present application provides an injectable formulation comprising polysorbate 80 and propylene glycol dicaprylate/dicaprate formulated for sustained release of amoxicillin and extension of the half-life, an injectable formulation comprising amoxicillin and an excipient formulated for delayed release of amoxicillin, an antibiotic composition for animals comprising said injectable formulation, and a method for treating a bacterial infection comprising the step of administering said injectable formulation subcutaneously or intramuscularly to a mammal other than a human.

Inventors

• 김태원
• 고제원
• 김진화
• 정지수
• 정은혜

Assignees

• 충남대학교산학협력단

Dates

Publication Date

20260513

Application Date

20241106

Claims (15)

1. An injectable formulation comprising amoxicillin and excipients, formulated for delayed release.
2. An injectable formulation according to claim 1, wherein the excipient comprises methacrylic acid copolymer, ethyl cellulose, hydroxypropyl methylcellulose (HPMC), Carbopol, sodium alginate, or a combination thereof.
3. An injectable formulation according to claim 1, wherein the injectable formulation further comprises bromhexine.
4. An injectable preparation comprising amoxicillin at a concentration of 150 to 200 mg/l as an active ingredient, Polysorbate 80 at a concentration of 0.5 to 2.5 mg/l; and It comprises propylene glycol dicaprylate/dicaprate at a concentration of 730 to 770 mg/l, and An injectable formulation formulated for sustained release and extension of the half-life of amoxicillin.
5. An injectable preparation according to claim 4, wherein the amoxicillin is amoxicillin hydrate.
6. An injectable formulation according to claim 4, wherein the injectable formulation further comprises an antioxidant and an organic solvent.
7. The injectable formulation of claim 4, wherein the injectable formulation comprises amoxicillin trihydrate at a concentration of 150 to 200 mg/l; polysorbate 80 at a concentration of 1.0 to 2.5 mg/l; propylene glycol dicaprylate/dicaprate at a concentration of 730 to 770 mg/l; butyl hydroxytoluene at a concentration of 0.05 to 0.15 mg/l; and an organic solvent at a concentration of 15 to 25 mg/l.
8. The injectable formulation of claim 4, wherein the injectable formulation comprises amoxicillin trihydrate at a concentration of 150 to 200 mg/l; polysorbate 80 at a concentration of 1.0 to 1.5 mg/l; propylene glycol dicaprylate/dicaprate at a concentration of 730 to 770 mg/l; butyl hydroxytoluene at a concentration of 0.05 to 0.15 mg/l; and an organic solvent at a concentration of 15 to 25 mg/l.
9. An injectable formulation according to claim 8, wherein the organic solvent is benzyl alcohol and tetraglycol.
10. In claim 4, the injectable formulation is for subcutaneous or intramuscular administration.
11. In claim 4, the injectable formulation is administered to a companion animal.
12. An antibiotic composition for animals comprising an injectable formulation of any one of claims 1 to 11.
13. An antibiotic composition for animals according to claim 12, wherein the composition is for the treatment of otitis externa or dermatitis.
14. A method for treating a bacterial infection, comprising the step of administering an injectable preparation of any one of claims 1 to 11 subcutaneously or intramuscularly to a mammal other than a human.
15. A method for treating a bacterial infection according to claim 14, wherein the bacterial infection is otitis externa or dermatitis.

Description

Antibiotics for companion animals comprising amoxicillin with improved pharmacokinetic properties and use thereof The present invention relates to an antibiotic for companion animals comprising amoxicillin and excipients having improved pharmacokinetic properties, and to the use thereof. Amoxicillin is also referred to as (2S,5R,6R)-6-{[(2R)-2-amino-2-(4-hydroxyphenyl)-acetyl]amino}3,3-dimethyl-7-oxo-4-thi-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, and is a compound belonging to the penicillin class of beta-lactam antibiotics that has a beta-lactam ring consisting of three carbon atoms and one nitrogen atom in its chemical structure. Amoxicillin is a crystalline powder that is white or pale yellow in color. It does not dissolve well in water, but its solubility increases in acidic solutions. Amoxicillin is a beta-lactam antibiotic that inhibits cell wall formation and has antibacterial activity against Gram-positive and Gram-negative bacteria. Specifically, it has inhibitory activity against Staphylococcus aureus, Streptococcus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Haemophilus influenzae, Escherichia coli, and Proteus (especially Proteus mirabilis). In addition, amoxicillin is known to be used in the treatment of otitis externa, otitis media, dermatitis, boils, carbuncles, cellulitis, impetigo, pyoderma, wound and postoperative secondary infections, erysipelas, pharyngitis, lymphadenitis, sinusitis, post-extraction infections, pneumonia, bronchitis, lung abscess, empyema, scarlet fever, bacterial endocarditis, pyelonephritis, cystitis, urethritis, gonococcal urethritis, peritonitis, liver abscess, typhoid fever, osteomyelitis, intrauterine infections, etc. Meanwhile, sustained-release or long-acting formulations refer to injectable formulations designed to allow for the continuous and uniform release of a drug within the body while maintaining its biological activity upon injection. Common manufacturing methods for these sustained-release formulations include coacervation, melt injection, spray drying, and solvent evaporation. Among these methods, solvent evaporation, classified into double emulsion evaporation (W/O/W emulsion) and single emulsion evaporation (O/W emulsion), is the most widely used. These conventional technologies still have the disadvantage of a high possibility of excessive initial release. Furthermore, when the active ingredient (drug) is dissolved in an organic solvent or water, it can form microspheres, leading to problems such as changes in the drug's physical properties, loss of stability, and low encapsulation efficiency (Korean Published Patent No. 10-2021-0099553). Against this technological backdrop, there is a need to develop sustained-release formulations that can maximize the inherent efficacy of antibiotics and reduce drug resistance caused by frequent administration. Figure 1 shows the results of blood concentration curves after drug administration, after subcutaneously injecting a long-acting candidate formulation (Experimental Example 1 and Experimental Example 3) according to one embodiment into a rat model. Figure 2 shows the results of confirming the level of antibacterial activity of the control group through an ex vivo time-kill curve evaluation. Figure 3 is the result of confirming the level of antibacterial activity of a long-acting candidate formulation (Experimental Example 1) according to one embodiment through an ex vivo time-kill curve evaluation. Figure 4 is the result of confirming the level of antibacterial activity of a long-acting candidate formulation (Experimental Example 2) according to one embodiment through an ex vivo time-kill curve evaluation. Figure 5 is the result of confirming the level of antibacterial activity of a long-acting candidate formulation (Experimental Example 3) according to one embodiment through an ex vivo time-kill curve evaluation. Figure 6 shows the results of re-verifying the level of antibacterial activity of the control group through an ex vivo time-kill curve evaluation. Figure 7 is the result of re-verifying the level of antibacterial activity of a long-acting candidate formulation (Experimental Example 3) according to one embodiment through an ex vivo time-kill curve evaluation. Figure 8 shows the results of blood concentration curves after drug administration, after intramuscularly injecting a long-acting intramuscular injection formulation (Experimental Example 5 and Experimental Example 6) according to one embodiment into a rat model. Figure 9 shows the results of blood concentration curves after drug administration, after intramuscular injection of the comparative example formulation into target animal models (n=9). Figure 10 shows the results of blood concentration curves after drug administration, after intramuscularly injecting a long-acting intramuscular injection formulation (Experimental Example 5) according to one embodiment into a target animal model. Figure 11 shows the results of blood concentr