Pharmaceutical Anit-Infective Composition for Inhalation

Abstract

A composition for inhalation, comprising at least: a) an effective amount of an antimicrobial aminoglycoside derivative or a salt thereof, and b) an effective amount of a biofilm modifier which is a macrolide derivative or a salt thereof.

Description

FIELD OF THE INVENTION[0001]The invention relates to pharmaceutical compositions for the treatment of lung infections caused by biofilm producing bacterial, fungal or viral pathogens.[0002]The invention discloses inhaled combinations of at least one antibiotic agent which is an aminoglycoside or a salt thereof and at least one biofilm modifier agent which is a macrolide or a salt thereof, for the treatment of recurrent lung infections associated with a biofilm.[0003]The compositions of the present invention are meant to be administered locally in the lungs of patients, said lung administration being performed using a dry powder inhaler system or a nebulizer.[0004]The weight ratio of each of said antibiotic and said biofilm modifier may be superior or equal to 10% of said dry powder inhaler. The weight ratio between the aminoglycoside and the macrolide in the compositions of the invention can be comprised between 0.2 and 5, and the total amount of both active ingredients per pharmace...

AI Technical Summary

Benefits of technology

The combination of aminoglycosides and macrolides in a dry powder inhalation form effectively targets biofilms, achieving high lung deposition and concentrations to kill pathogens and disrupt biofilms, while minimizing systemic exposure and adverse effects, thus providing an efficient and safe treatment for lung infections.

Problems solved by technology

Antibiotic resistance and persistent infections refractory to per os or injected treatments are a major problem in bacteriological transmissions, resistance to eradication and ultimately pathogenesis.

In particular, biofilms constitute a growing problem for the treatment of respiratory diseases associated with infection like cystic fibrosis, diffuse panbronchiolitis, exacerbation of chronic obstructive pulmonary diseases, pneumonia, etc. . . . The treatments of those diseases with antibiotics become consequently more and more difficult due to the resistance offered by said biofilm.

Aminoglycoside antibiotics are very active antimicrobial agents but their use has been limited because of their high frequence of serious and irreversible adverse events associated with their use.

However, due to low respiratory fraction compositions administered through nebulisation (5 to 8% of the nominal dose), the nominal dose to administer (300 mg of Tobramycin b.i.d.) is still too high and can be responsible of a significant frequency and / or severity of side-effects.

Although, aminoglycoside antibiotics are very effective against several planktonic bacteria, they are much less effective if not ineffective against the same bacterial which have formed a biofilm.

While macrolides antibiotics are mostly available as oral dosage forms containing several hundreds of milligrams of the antibiotic, no inhaled form has been available up to now, because amounts of hundreds of mg are impossible to administer ambulatorily by inhalation through systems like dry powder inhalers or metered dose inhalers.

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