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A pharmaceutical composition capable of resisting chronic infection and biofilm bacteria and its application

A technology of biofilm and composition, which is applied in the field of medicine, can solve the problems of poor activity of non-growth persistent bacteria and limited therapeutic effect, and achieve the effects of wide application range, clearing infection and alleviating inflammation

Active Publication Date: 2021-08-03
THE AFFILIATED HOSPITAL OF QINGDAO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite their clinical significance, most current antibiotic treatments primarily kill growing bacteria, are less active against non-growing persisters, and have limited efficacy in the treatment of persistent infections, including biofilm infections

Method used

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  • A pharmaceutical composition capable of resisting chronic infection and biofilm bacteria and its application
  • A pharmaceutical composition capable of resisting chronic infection and biofilm bacteria and its application
  • A pharmaceutical composition capable of resisting chronic infection and biofilm bacteria and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] In the existing technology, vancomycin is usually used for the treatment of infection. Although vancomycin is very effective in killing methicillin-resistant Staphylococcus aureus in vitro, in terms of clearing chronic Staphylococcus aureus infection, vancomycin is single Treatment may not be the most effective. At least 6 weeks if vancomycin is used as monotherapy or drug combination therapy; up to 10 days if combination therapy is used, such as combination of doxycycline and rifampicin; combination of vancomycin, gentamicin and Rifampicin, treated for at least 6 weeks, combined drug can also be used to treat chronic infection, exemplarily, it is used to treat conditions such as osteomyelitis and artificial joint infection.

[0052] In this experiment, four groups of different drugs were used for treatment, and the effect of the drugs was verified by experiments. Among them, no drug (i.e., blank none) was used as the first group of experiments, and vancomycin (Vancomyc...

Embodiment 2

[0055] Biofilms of S. aureus strain USA300, a common circulating strain of methicillin-resistant S. aureus (CA-MRSA), were grown on 96-well plates (achieved by microtiter plate biofilms). In order to determine an effective combination, the present invention has tested multiple drug combinations in an in vitro biofilm model: the first group is a blank test (none), the second group is vancomycin (Vancomycin, Van), daptomycin (Daptomycin, Dap) and Tosufloxacin (Tosufloxacin, Tosu) combination, the third group is the combination of Meropenem (Meropenem, Mer), Daptomycin (Daptomycin, Dap), Tosufloxacin (Tosufloxacin, Tosu) Medication, the fourth group is vancomycin (Vancomycin, Van), daptomycin (Daptomycin, Dap) and Clinafloxacin (Clinafloxacin, Clina) combined medication, the fifth group is meropenem (Meropenem, Mer), daptomycin Combination of Daptomycin (Dap) and Clinafloxacin (Clina). Through five groups of experiments, the results are as follows: figure 2 shown. in figure...

Embodiment 3

[0064] This example verifies that clinfloxacin has the best resistance activity among the anti-fluoroquinolones. In this example, the anti-biofilm activity of different fluoroquinolone antibiotics was ranked to determine whether the anti-biofilm activity of clinfloxacin used in the combined drug was unique to the drug itself, or could be replaced by other fluoroquinolone antibiotics. To test the idea, this example used the Newman's S. aureus strain, since this strain is susceptible to most fluoroquinolones, which would remove any confounding factors due to inherent resistance. For other fluoroquinolones, one of ciprofloxacin, levofloxacin, and moxifloxacin was combined with meropenem and daptomycin; after 4 days of combined medication, each drug combination produced certain anti-persistence or anti-biofilm active, and the combination with clinfloxacin is the most effective. In contrast, biofilms treated with other quinolones still contained 10 4 -10 8 CFU / ml (each millilite...

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Abstract

The invention provides a pharmaceutical composition capable of resisting chronic infection and biofilm bacteria, the active ingredients of which include clinfloxacin and at least one antibiotic selected from daptomycin and oritavancin; The active ingredient of the composition also includes an additional antibiotic, and the additional antibiotic is at least one antibiotic selected from vancomycin and meropenem. By using the pharmaceutical composition of the present invention, persistent bacteria can be completely eliminated in vitro, and persistent biofilm infection can be effectively eliminated, the lesion can be cured, and inflammation can be relieved; in addition, the pharmaceutical composition of the present invention is suitable for infections in vivo, in vitro, and on the body surface Treatment has a wide range of applications.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to a pharmaceutical composition capable of resisting chronic infection and biofilm bacteria and its application. Background technique [0002] Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in healthcare and community-acquired S. aureus infections. It is known that the mortality rate associated with MRSA infection is as high as 40%. Staphylococcus aureus is an opportunistic pathogen that is the most common cause of skin infections and can also cause chronic infections such as endocarditis, osteomyelitis, and persistent infections of artificial joints. Indwelling devices in particular are more conducive to biofilm formation, complicating treatment and leading to long-term chronic infections that are difficult to completely eradicate with existing treatments. Globally, persistent and chronic infections are an enormous public health burden because they prolong hospital...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K38/10A61K38/14A61P31/04A61K31/4709A61K31/407
CPCA61K31/407A61K31/4709A61K38/10A61K38/14A61K45/06A61P31/04A61K2300/00
Inventor 张颖邢东明陈五军宋正明
Owner THE AFFILIATED HOSPITAL OF QINGDAO UNIV
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