Dalbavancin compositions for treatment of bacterial infections

Abstract

The invention provides methods and compositions for treatment of bacterial infections. Methods of the invention include administration of a mixture of dalbavancin multimers and monomers for treatment of a bacterial infection, in particular a Gram-positive bacterial infection of skin and soft tissue. Compositions comprise a mixture of dalbavancin multimer and monomer and a stabilizer, such as dextrose.

1 . A pharmaceutically acceptable aqueous composition comprising dalbavancin and dextrose wherein said composition comprises a mixture of dalbavancin monomers and multimers, wherein the concentration of said dalbavancin in said aqueous composition is from about 0.1 mg/mL to about 100 mg/mL. 
   
   
       2 . A pharmaceutically acceptable aqueous composition comprising dalbavancin and deionized water wherein said composition comprises a mixture of dalbavancin monomers and multimers, wherein the concentration of said dalbavancin in said aqueous composition is from about 0.1 mg/mL to about 100 mg/mL. 
   
   
       3 . A pharmaceutically acceptable aqueous composition comprising dalbavancin and a stabilizer wherein said composition comprises a mixture of dalbavancin monomers and multimers, wherein the concentration of said dalbavancin in said aqueous composition is from about 0.1 mg/mL to about 100 mg/mL. 
   
   
       4 . A pharmaceutically acceptable aqueous composition comprising dalbavancin, dextrose, deionized water, and a stabilizer other than dextrose wherein said composition comprises a mixture of dalbavancin monomers and multimers, wherein the concentration of said dalbavancin in said aqueous composition is from about 0.1 mg/mL to about 100 mg/mL. 
   
   
       5 . The aqueous composition according to  claim 1 , wherein said aqueous composition is deionized. 
   
   
       6 . The aqueous composition according to  claim 1 , wherein the pH of the aqueous solution is at least about 3.0. 
   
   
       7 . The aqueous composition according to  claim 6 , wherein the pH of the aqueous solution is from about 3.0 to about 5.5. 
   
   
       8 . The aqueous composition according to  claim 7 , wherein the pH of the aqueous solution is about 4.5. 
   
   
       9 . The aqueous composition according to  claim 1 , wherein the composition has a multimer to monomer ratio in solution that is preferably at least about 2:1. 
   
   
       10 . The aqueous composition according to  claim 9 , wherein the multimer to monomer ratio is about 2:1 to about 8:1. 
   
   
       11 . The aqueous composition according to  claim 10 , wherein the multimer to monomer ratio is about 4:1 to about 8:1. 
   
   
       12 . The aqueous composition according to  claim 11 , wherein the multimer to monomer ratio is between about 6:1 to about 8:1 
   
   
       13 . The aqueous composition according to  claim 12 , wherein the multimer to monomer ratio is between about 6:1 to about 7:1. 
   
   
       14 . The aqueous composition according to anyone of  claims 1  to  4 , wherein the dalbavancin multimer is a dalbavancin dimer. 
   
   
       15 . The aqueous composition according to  claim 1 , wherein the multimer Is stabilized by an Ionic Interaction. 
   
   
       16 . The aqueous composition according to  claim 1 , wherein the multimer is stabilized by a hydrophobic interaction. 
   
   
       17 . The aqueous composition according to  claim 1 , wherein the multimer is stabilized by a combination of ionic and hydrophobic Interactions. 
   
   
       18 . The aqueous composition according to  claim 1 , further comprising an antibiotic that is not dalbavancin. 
   
   
       19 . The aqueous composition according to  claim 18 , wherein the antibiotic that is not dalbavancin is effective against a Gram negative bacterium. 
   
   
       20 . A method for treating a bacterial infection in an individual in need thereof, the method comprising administering to the individual a therapeutically effective dose of the composition according to  claim 1 . 
   
   
       21 . The method according to  claim 20 , wherein the administration is parenteral administration. 
   
   
       22 . The method according to  claim 21 , wherein the parenteral administration comprises intravenous administration. 
   
   
       23 . The method according to  claim 22 , wherein administration occurs over at least about 30 minutes. 
   
   
       24 . The method according to  claim 23 , wherein the dose is from about 0.5 to about 1 gram of dalbavancin. 
   
   
       25 . The method according to  claim 20 , wherein the bacterial infection comprises a Gram positive bacterium. 
   
   
       26 . The method according to  claim 25 , wherein said Gram-positive bacterium is a penicillin-resistant bacterium. 
   
   
       27 . The method according to  claim 26 , wherein the bacterial infection comprises a skin and soft tissue (SSTI) infection. 
   
   
       28 . The method according to  claim 27 , wherein said SSTI comprises  Staphylococcus aureus.    
   
   
       29 . The method according to  claim 27 , wherein said SSTI comprises  Streptococcus pyogenes.    
   
   
       30 . The method according to  claim 20 , wherein said bacterial infection is reduced. 
   
   
       31 . The method according to  claim 20 , wherein said bacterial infection is eliminated. 
   
   
       32 . The method according to  claim 20 , wherein said individual Is a mammal. 
   
   
       33 . The method according to  claim 32 , wherein said mammal is a human. 
   
   
       34 . The method according to  claim 20 , further comprising administering an antibiotic that is not dalbavancin to the individual. 
   
   
       35 . The method according to  claim 34 , wherein the antibiotic that is not dalbavancin is effective against a Gram negative bacterium. 
   
   
       36 - 42 . (canceled) 
   
   
       43 . The aqueous composition according to  claim 1  wherein the concentration of said dalbavancin in said aqueous composition is from about 1 mg/mL to about 10 mg/mL. 
   
   
       44 . The aqueous composition according to  claim 2  wherein the concentration of said dalbavancin in said aqueous composition is from about 1 mg/mL to about 10 mg/mL. 
   
   
       45 . The aqueous composition according to  claim 3  wherein the concentration of said dalbavancin in said aqueous composition is from about 1 mg/mL to about 10 mg/mL. 
   
   
       46 . The aqueous composition according to  claim 4  wherein the concentration of said dalbavancin in said aqueous composition is from about 1 mg/mL to about 10 mg/mL.