Pharmaceutical anti-infective composition for inhalation

Abstract

An anti-infective composition for inhalation, containing, at least an effective amount of an antimicrobial aminoglycoside compound or a salt thereof; and an effective amount of a biofilm modifier which is a macrolide compound or salt thereof.

What is claimed is: 
     
         1 . An inhalation composition for the treatment of lung disease caused by biofilm producing bacteria, fungal or viral pathogens, comprising at least:
 (a) an antimicrobial aminoglycoside compound or a salt thereof, and   (b) a biofilm modifier which is a macrolide selected from the group consisting of azythromycin,   clarithromycin and erythromycin; or a pharmaceutical salt thereof or both;   
       said components a) and b) being in an amount sufficient to disrupt said biofilm and treat said disease. 
     
     
         2 . The composition of  claim 1 , in a form of a dry powder. 
     
     
         3 . The composition according to  claim 1 , in a form of a suspension, solution, or a combination thereof. 
     
     
         4 . The composition of  claim 1 , wherein a ratio aminoglycoside/macrolide is between 0.2 to 5. 
     
     
         5 . The composition of  claim 4 , wherein the ratio is between 0.3 and 3. 
     
     
         6 . The composition of  claim 4 , wherein the ratio is between 0.8 and 2. 
     
     
         7 . The composition of  claim 1 , wherein the total amount of active ingredients represents more than 20% of the composition. 
     
     
         8 . The composition  claim 7 , wherein the total amount of the active ingredients is more than 30% of the composition. 
     
     
         9 . The composition of  claim 8 , wherein the total amount of the active ingredients is more than 40% of the composition. 
     
     
         10 . The composition of  claim 1 , containing at least one or more pharmaceutically acceptable excipients for inhalation to the lungs. 
     
     
         11 . The composition of  claim 10 , wherein at least one of said pharmaceutically acceptable excipients is a carbohydrate or a mixture of two or more carbohydrates. 
     
     
         12 . The composition of  claim 11 , wherein at least one of said pharmaceutically acceptable carbohydrate comprises anhydrous lactose, lactose monohydrate, mannitol, xylitol, dextrose, saccharose, a cyclodextrin compound or a mixture thereof. 
     
     
         13 . The composition of  claim 10 , wherein at least one of said pharmaceutically acceptable excipient is a lipidic excipient. 
     
     
         14 . The composition of  claim 13 , wherein at least one of said lipidic excipients is selected from the group consisting of cholesterol compounds, phospholipid, ethers of fatty alcohols, esters of fatty acids, hydrogenated oils, polyoxyethylenated compounds and esters of glycerol. 
     
     
         15 . The composition of  claim 14 , wherein said composition contains a mixture of cholesterol or a cholesterol compound and a phospholipid or a phospholipid. 
     
     
         16 . The composition of  claim 1 , further containing one or more antioxidant(s) selected from the group consisting of cysteine and/or esters thereof ascorbic acid and/or salts thereof, tocopherol esters, propylgallate, butylhydroxyanisole, or butylhydroxytoluene. 
     
     
         17 . The composition of  claim 1 , wherein the aminoglyscoside is selected from the group consisting of Tobramycin, Kanamycin, Streptomycin, Gentamicin, Amikacin, Arbekacin, Bekanamycin, Astromycin, Dihydrostreptomycin, Framycetin, Neomycin, Netilmicin, lsepamicin, Micronomicin, Sisomicin or a pharmaceutically acceptable salt thereof. 
     
     
         18 . The composition of  claim 1 , wherein the aminoglyscoside compound is Tobramycin or a salt thereof and the macrolide compound is clarithromycin or a salt thereof, said composition being free of another antimicrobial agent. 
     
     
         19 . The composition of  claim 1 , wherein said composition is free of excipients. 
     
     
         20 . The composition of  claim 2 , wherein said dry powder composition is filled in pharmaceutically acceptable capsules. 
     
     
         21 . The composition of  claim 20 , wherein said pharmaceutically acceptable capsule comprises, as main polymer, gelatin, hydroxypropylcellulose or starch. 
     
     
         22 . The composition of  claim 2 , wherein the said dry powder composition is filled into a multidose dry powder inhaler device. 
     
     
         23 . The composition of  claim 1 , which is filled into a nebulizer inhaler. 
     
     
         24 . The composition of  claim 1 , wherein the biofilm produced is a mature biofilm. 
     
     
         25 . The composition of  claim 1 , whereby each active ingredient (a) and (b) are delivered in an amount of from 5 to 20 times above the MIC for the pathogens causing the infection.