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.

1 . 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 salt thereof.   
   
   
       2 . The composition according to  claim 1  in the form of a dry powder. 
   
   
       3 . The composition according to  claim 1  in the form of a liquid, either a suspension, a solution, or a combination thereof, 
   
   
       4 . The composition according to  claim 1 , wherein the ratio (weight/weight) of each of said aminoglycoside derivative and said macrolide is superior or equal to 10% of said composition. 
   
   
       5 . The composition according to  claim 1 , wherein the ratio (weight/weight) aminoglycoside/macrolide is between 0.2 to 5. 
   
   
       6 . The composition according to  claim 1 , wherein the ratio of the sum of the active ingredients to the composition represents more than 20% (weight/weight) of the composition. 
   
   
       7 . The composition according to  claim 1  containing at least one or several pharmaceutically acceptable excipients. 
   
   
       8 . The composition according to  claim 7 , wherein at least one of said pharmaceutically acceptable excipients is a carbohydrate or a mixture of two or more carbohydrates. 
   
   
       9 . The composition according to  claim 8 , wherein at least one of said pharmaceutically acceptable carbohydrate is anhydrous lactose, lactose monhydrate, mannitol, xylitol, dextrose, saccharose, a cyclodextrin derivative or a mixture thereof. 
   
   
       10 . The composition according to  claim 7 , wherein at least one of said pharmaceutically acceptable excipientsis a lipidic excipient. 
   
   
       11 . The composition of according to  claim 10 , wherein at least one of said lipidic excipients is chosen from the group comprising cholesterol and derivatives, phospholipid, ethers of fatty alcohols, esters of fatty acids, hydrogenated oils, polyoxyethylenated derivatives, esters of glycerol. 
   
   
       12 . The composition according to  claim 11 , wherein said composition contains a mixture of cholesterol or a cholesterol derivative and a phospholipid or a phospho lipid derivative. 
   
   
       13 . The composition according to  claim 1 , further containing one or more chelating agent(s). 
   
   
       14 . The composition according to  claim 13 , wherein the chelating agent is edetic acid, citric acid, malic acid or a salt thereof. 
   
   
       15 . The composition according to  claim 1 , further containing one or more antioxidant(s). 
   
   
       16 . The composition according to  claim 15 , wherein at least one antioxidant is chosen from a cystein derivative, the derivatives of ascorbic acid, the derivatives of tocopherol, propylgallate, butylhydroxyanisole, or butylhydroxytoluene. 
   
   
       17 . The composition according to  claim 1 , wherein the aminoglyscoside derivative is Tobramycin, Kanamycin, Streptomycin, Gentamicin, Amikacin, Apramycin, Arbekacin, Bekanamycin, Astromycin, Dihydrostreptomycin, Framycetin, Neomycin, Netilmicin, Isepamicin, Micronomicin, Sisomicin or their pharmaceutically acceptable salts. 
   
   
       18 . The composition according to  claim 1 , wherein the macrolide derivative is a biofilm modifier macrolide or an antibiotic macrolide, and is advantageously selected from the group consisting of Clarithromycin, Azithromycin, Roxithromycin, Erythromycin, Telithromycin, Dirithromycin, Flurithromycin, Josamycin, Kitasamycin, Midecamycin, Dalfopristin, Oleandomycin, Midecamycin, Pristinamycin, Rokitamycin, Spiramycin, Tilmicosin, Troleandomycin, Tylosin, Virginiamycin, and their pharmaceutically acceptable salts. 
   
   
       19 . The composition according to  claim 1 , wherein the aminoglyscoside derivative is Tobramycin or a salt thereof and the macrolide derivative is clarithromycin or a salt thereof, said composition being free of another antimicrobial agent. 
   
   
       20 . The composition according to  claim 1  claim, wherein said composition is free of excipients. 
   
   
       21 . The composition according to  claim 2 , wherein said dry powder composition is filled in pharmaceutically acceptable capsules. 
   
   
       22 . The composition of according to  claim 19 , wherein said pharmaceutically acceptable capsule contains, as main polymer, gelatin, hydroxypropylcellulose or starch. 
   
   
       23 . The composition according to  claim 2 , wherein said dry powder composition is filled into a multidose dry powder inhaler device. 
   
   
       24 . The composition according to  claim 4 , wherein the ratio (weight/weight) of each of said aminoglycoside derivative and said macrolide is superior or equal to 15-90% of said composition. 
   
   
       25 . The composition according to  claim 1 , wherein the ratio (weight/weight) aminoglycoside/macrolide is between 0.3 to 3. 
   
   
       26 . The composition according to  claim 1 , wherein the ratio (weight/weight) aminoglycoside/macrolide is between 0.8 to 2. 
   
   
       27 . The composition according to  claim 1 , wherein the ratio of the sum of the active ingredients to the composition represents more than 40%.