Arylamide compounds and compositions and uses thereof

Abstract

The present invention discloses ophthalmic and otic compositions of facially amphiphilic antimicrobial polymers and oligomers and their uses, including their use in methods for treating and preventing ophthalmic infections and otic infections in humans and animals.

1 - 15 . (canceled) 
     
     
         16 . A method a treating a bacterial infection in a mammal comprising administering to the mammal in need thereof an effective amount of a pharmaceutical composition comprising a compound having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         17 . The method of  claim 16  wherein the composition further comprises Tris-buffered saline. 
     
     
         18 . The method of  claim 16  wherein the composition further comprises Farnesol, polyethylene glycol, and Tris-buffered saline. 
     
     
         19 . The method of  claim 16  wherein the composition further comprises an additional medicament. 
     
     
         20 . The method of  claim 19  wherein the additional medicament is chosen from an antibiotic, an anti-inflammatory agent, an anesthetic agent, an anti-allergic agent, an acetylcholine blocking agent, an adrenergic agonist, a beta-adrenergic blocking agent, an anti-glaucoma agent, and an anti-hypertensive agent. 
     
     
         21 . The method of  claim 20  wherein the antibiotic is chosen from an aminoglycoside, a cephalosporin, a diaminopyridine, a fluoroquinolone, a sulfonamide, and a tetracycline. 
     
     
         22 . The method of  claim 20  wherein the antibiotic is chosen from amikacin, azithromycin, cefixime, cefoperazone, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, chloramphenicol, ciprofloxacin, clindamycin, colistin, domeclocycline, doxycycline, erythromycin, gentamicin, mafenide, methacycline, minocycline, neomycin, norfloxacin, ofloxacin, oxytetracycline, polymyxin B, pyrimethamine, silver sulfadiazine, sulfacetamide, sulfisoxazole, tetracycline, tobramycin, and trimethoprim. 
     
     
         23 . The method of  claim 20  wherein the anti-inflammatory agent is a steroidal agent or a non-steroidal agent. 
     
     
         24 . The method of  claim 23  wherein the steroidal agent is chosen from dexamethasone, rimexolone, prednisolone, fluorometholone, and hydrocortisone, and wherein the non-steroidal agent is chosen from a cyclooxygenase type I or type II inhibitor, a PAF antagonist, a PDE IV inhibitor, and an inhibitor of cytokine production. 
     
     
         25 . The method of  claim 24  wherein the cyclooxygenase type I or type II inhibitor is chosen from diclofenac, flurbiprofen, ketorolac, suprofen, nepafenac, amfenac, indomethacin, naproxen, ibuprofen, bromfenac, ketoprofen, meclofenamate, piroxicam, sulindac, mefanamic acid, diflusinal, oxaprozin, tolmetin, fenoprofen, benoxaprofen, nabumetome, etodolac, phenylbutazone, aspirin, oxyphenbutazone, tenoxicam, carprofen, vioxx, celecoxib, and etodolac. 
     
     
         26 . The method of  claim 24  wherein the PAF antagonist is chosen from apafant, bepafant, minopafant, nupafant, and modipafant. 
     
     
         27 . The method  claim 24  wherein the PDE IV inhibitor is chosen from ariflo, torbafylline, rolipram, filaminast, piclamilast, cipamfylline, and roflumilast. 
     
     
         28 . The method  claim 20  wherein the anti-allergic agent is pemirolast or olopatadine. 
     
     
         29 . The method of  claim 20  wherein the anti-allergic agent is a corticosteroid. 
     
     
         30 . The method of  claim 29  wherein the corticosteroid is chosen from prednisolone, fluorometholone, loteprenol, and dexamethasone. 
     
     
         31 . The method of  claim 16  wherein the pharmaceutically acceptable salt is a hydrochloride acid addition salt. 
     
     
         32 . The method of  claim 16  wherein the bacteria is chosen from fluoroquinolone-susceptible  Staphylococcus aureus , fluoroquinolone-resistant  Staphylococcus aureus , fluoroquinolone-susceptible and coagulase-negative  Staphylococcus epidermidis , fluoroquinolone-resistant and coagulase-negative  Staphylococcus epidermidis, Staphylococcus pneumonia, Moraxella catarrhalis, Staphylococcus viridans, Serratia marcescens, Pseudomonas aereginosa , and  Haemophilus influenza.