阅读说明：本技术 抗菌剂与β-内酰胺酶抑制剂组合物及其应用 (Antibacterial agent and beta-lactamase inhibitor composition and application thereof ) 是由 苗得足 胡清文 李雪改 曾丽丽 于 2019-08-28 设计创作，主要内容包括：本发明属于抗感染药物领域,具体涉及一种抗菌剂与β-内酰胺酶抑制剂组合物及其应用。所述的组合物包括A：美洛西林或其药学上可接受的盐,优选美洛西林钠；B：阿维巴坦或其药学上可接受的盐,优选阿维巴坦钠。其中：所述的A与B的质量比为10-1:1-10。本发明通过阿维巴坦保护美洛西林不被β-内酰胺酶水解,增强其杀菌效果,解决了细菌对美洛西林耐药的问题,可用于制备美洛西林敏感菌以及产β-内酰胺酶耐药菌引起的呼吸系统、泌尿系统、消化系统、妇科和生殖器官感染的药物。(The invention belongs to the field of anti-infective drugs, and particularly relates to an antibacterial agent and beta-lactamase inhibitor composition and application thereof. The composition comprises A: mezlocillin or a pharmaceutically acceptable salt thereof, preferably mezlocillin sodium; b: abamebactam or a pharmaceutically acceptable salt thereof, preferably abamectin sodium. Wherein: the mass ratio of A to B is 10-1: 1-10. The invention protects mezlocillin from being hydrolyzed by beta-lactamase through the abamectin, enhances the sterilization effect, solves the problem of drug resistance of bacteria to mezlocillin, and can be used for preparing drugs for infection of respiratory system, urinary system, digestive system, gynecologic and reproductive organs caused by mezlocillin sensitive bacteria and beta-lactamase drug-resistant bacteria.)

1. An antibacterial and beta-lactamase inhibitor composition, characterized by: the method comprises the following steps: mezlocillin or a pharmaceutically acceptable salt thereof; b: avibactam or a pharmaceutically acceptable salt thereof.

2. The antibacterial and beta-lactamase inhibitor composition according to claim 1, wherein: a is mezlocillin sodium, and B is abamectin sodium.

3. The antibacterial and beta-lactamase inhibitor composition according to claim 1 or 2, wherein: the mass ratio of A to B is 10-1: 1-10.

4. The antibacterial and beta-lactamase inhibitor composition according to claim 1 or 2, wherein: the mass ratio of A to B is 2:1-9: 1.

5. The antibacterial and beta-lactamase inhibitor composition according to claim 1 or 2, wherein: the A and the B are independently or in the form of a mixture.

6. The antibacterial and beta-lactamase inhibitor composition according to claim 1 or 2, wherein: the mass of A in the composition of unit dose is 0.1-20 g.

7. The antibacterial and beta-lactamase inhibitor composition according to claim 1 or 2, wherein: the mass of B in the composition is 0.01-10g per unit dose.

8. The antibacterial and beta-lactamase inhibitor composition according to claim 1 or 2, wherein: also comprises pharmaceutically acceptable auxiliary materials.

9. The formulation of an antibacterial agent and a beta-lactamase inhibitor combination according to claim 1 or 2, wherein: the composition preparation is powder for injection.

10. Use of an antibacterial agent according to claim 1 or 2 in combination with a beta-lactamase inhibitor, wherein: can be used for preparing medicines for treating respiratory system infection, urinary system infection, digestive system infection, gynecological infection and reproductive organ infection caused by mezlocillin sensitive bacteria and/or beta-lactamase drug-resistant bacteria.

Technical Field

The invention belongs to the field of anti-infective drugs, and particularly relates to an antibacterial agent and beta-lactamase inhibitor composition and application thereof.

Background

The semi-synthetic penicillin antibacterial drugs are widely used clinically, and achieve the treatment effect which is difficult to achieve by the traditional antibiotic drugs. However, due to the long-term clinical widespread use and even the abuse of antibiotic drugs, the drug resistance of bacteria to antibiotic drugs is getting stronger and stronger. Mezlocillin is a semi-synthetic benzimidazole penicillin broad-spectrum antibiotic, has antibacterial effects on pseudomonas aeruginosa, escherichia coli, pneumonia bacillus, proteus bacillus, enterobacter, citrobacter, serratia, acinetobacter and gram-positive coccus sensitive to penicillin, and has a bactericidal effect in large dose. The antibacterial activity to Escherichia coli, Enterobacter, pneumonia bacillus, Citrobacter, Serratia and Acinetobacter is stronger than carbenicillin and ampicillin; the antibacterial activity to the indole positive proteus and the pseudomonas aeruginosa is stronger than that to the carbenicillin and the sulbenicillin; the antibacterial activity against gram-positive bacteria such as Staphylococcus aureus is similar to that of carbenicillin, while the antibacterial activity against Streptococcus faecalis superior to that of carbenicillin and sulbenicillin. Has good antibacterial effect on most anaerobic bacteria such as bacteroides fragilis. It has antibacterial effect by interfering with synthesis of bacterial cell wall, is difficult to be absorbed from gastrointestinal tract, and is usually administered parenterally by sodium salt thereof.

Mezlocillin has a beta-lactam structure, and beta-lactamase in vivo can accelerate the hydrolysis of mezlocillin, so that the curative effect is reduced. Plasmid delivery produces beta-lactamase, which causes some drugs to hydrolyze and inactivate the beta-lactam ring, and is the main mode for pathogenic bacteria to resist some common beta-lactam antibiotics (penicillins and cephalosporins).

Disclosure of Invention

The technical problem solved by the invention is as follows: the defects of the prior art are overcome, and the composition of the antibacterial agent and the beta-lactamase inhibitor is provided, so that mezlocillin is protected from being hydrolyzed by beta-lactamase, the sterilization effect of mezlocillin is enhanced, and the problem of drug resistance of bacteria to mezlocillin is solved; the invention also provides the application of the medicine, and the medicine can be used for preparing medicines for treating respiratory system, urinary system, digestive system, gynecological and reproductive organ infections caused by mezlocillin sensitive bacteria and beta-lactamase drug-resistant bacteria.

The antibacterial agent and beta-lactamase inhibitor composition comprises A: mezlocillin or a pharmaceutically acceptable salt thereof, preferably mezlocillin sodium; b: abamebactam or a pharmaceutically acceptable salt thereof, preferably abamectin sodium. Wherein: the mass ratio of A to B is 10-1: 1-10.

Preferably, the mass ratio of A to B is 2:1-9: 1.

Further preferably, the mass ratio of A to B is 4:1, and the synergistic effect is optimal at the preferred mass ratio.

A and B are independently or in mixture, A and B can be not mixed before use, and are independently packaged and are respectively applied or mixed to a subject at the time of use; or A and B can be a mixture, and when in use, the mixture is directly applied to a subject.

Preferably, the mass of A in a unit dose of the composition is from 0.1 to 20 g.

Preferably, the mass of B in a unit dose of the composition is 0.01-10 g.

The composition of the antibacterial agent and the beta-lactamase inhibitor can also comprise pharmaceutically acceptable auxiliary materials, and the addition amount of the auxiliary materials can be added according to actual requirements.

Preferably, the pharmaceutical composition of the antibacterial agent and the beta-lactamase inhibitor can be used as an active ingredient and pharmaceutically acceptable auxiliary materials to prepare any preparation suitable for clinical application, preferably powder for injection.

The application of the antibacterial agent and beta-lactamase inhibitor composition can be used for preparing medicines for treating moderate and severe infectious diseases caused by mezlocillin sensitive bacteria and beta-lactamase drug-resistant bacteria, wherein the infectious diseases comprise: (1) respiratory infections: such as otitis media, sinusitis, tonsillitis, pharyngitis, pneumonia, acute and chronic bronchitis acute attack, bronchiectasis, empyema, lung abscess, etc.; (2) urogenital infections: such as pyelonephritis, cystitis, and urethritis; (3) infection of the abdominal cavity: such as biliary tract infections, etc.; (4) skin and soft tissue infections: such as cellulitis, wound infection, furunculosis, pyogenic dermatitis, and impetigo; (5) venereal disease: gonorrhea, etc.; (6) pelvic infection: gynecological infection, puerperal infection, etc.; (7) severe systemic infection: such as meningitis, bacterial endocarditis, peritonitis, sepsis, etc.

Abamebactam belongs to a diazabicyclooctanone compound, is a novel beta-lactamase inhibitor, has long-acting effect and covalent bonding with enzyme reversibility, and does not induce the effect of beta-lactamase compared with three marketed beta-lactamase inhibitors, namely Clavulanic acid (Clavulanic acid), Sulbactam (Sulbactam) and Tazobactam (Tazobactam). The abamectin can prevent the drug-resistant bacteria from damaging the penicillin and cephalosporin antibiotics, and has obvious synergistic effect with the penicillin and cephalosporin antibiotics.

Compared with the prior art, the invention has the following beneficial effects:

the invention can protect mezlocillin from being hydrolyzed by beta-lactamase through the synergistic effect of the abamectin or the pharmaceutically acceptable salt thereof and the mezlocillin or the pharmaceutically acceptable salt thereof, enhance the sterilization effect and solve the problem of drug resistance of bacteria to the mezlocillin.

Detailed Description

The present invention will be further described with reference to the following examples.