Encholeated antifungal compounds for central nervous system delivery and treatment of cryptococcus infections

Abstract

The present application is directed to a cochleate composition including one or more cochleates and at least two anti-fungal compounds selected from amphotericin B, 5-flucytosine, fluconazole, ketoconazole, ravuconazole, albaconazole, itraconazole, oposaconazole, isavuconazole and/or voriconazole. Methods of using the antifungal cochleate formulations are also disclosed.

1 - 30 . (canceled) 
     
     
         31 . An antifungal cochleate composition, comprising:
 (a) one or more cochleates and a therapeutically effective amount of a first antifungal compound, wherein the first antifungal compound is amphotericin B; and   (b) a therapeutically effective amount of a second antifungal compound, wherein the second antifungal compound is selected from the group consisting of 5-Flucytosine, fluconazole, ketoconazole, ravuconazole, albaconazole, itraconazole, posaconazole, isavuconazole and voriconazole;   wherein the first and second antifungal compounds are the only two antifungal compounds in the composition,   wherein the composition is formulated for oral administration.   
     
     
         32 . The antifungal cochleate composition of  claim 31 , wherein the second antifungal compound is 5-Flucocytosine or fluconazole, and wherein the 5-Flucocytosine or fluconazole is unencochleated. 
     
     
         33 . The antifungal cochleate composition of  claim 31 , wherein the only two antifungal compounds are encochleated amphotericin B and 5-Flucytosine, and wherein the 5-Flucytosine is encochleated or unenchochleated. 
     
     
         34 . The antifungal cochleate composition of  claim 31 , wherein the second antifungal compound is 5-Flucytosine, and wherein the 5-Flucytosine is unencochleated. 
     
     
         35 . The antifungal cochleate composition of  claim 31 , wherein the only two antifungal compounds are encochleated amphotericin B and fluconazole, wherein the fluconazole is encochleated or unencochleated. 
     
     
         36 . The antifungal cochleate composition of  claim 31 , wherein the second antifungal compound is fluconazole, and wherein the fluconazole is unencochleated. 
     
     
         37 . The antifungal cochleate composition of  claim 31 , wherein the first and second antifungal compounds are encochleated. 
     
     
         38 . The antifungal cochleate composition of  claim 31 , wherein the first and second antifungal compounds are formulated within the same cochleate. 
     
     
         39 . The antifungal cochleate composition of  claim 31 , wherein the composition is formulated for delivery to the central nervous system. 
     
     
         40 . The antifungal cochleate composition of  claim 39 , wherein the cochleate composition is capable of reducing fungal colony forming units (CFU's) in the brain by at least 8% after oral administration. 
     
     
         41 . The antifungal cochleate composition of  claim 40 , wherein the cochleate composition is capable of reducing CFU's in the brain by at least 50% after oral administration. 
     
     
         42 . The antifungal cochleate composition of  claim 31 , wherein at least one of the only two antifungal compounds is encochleated in a geodate cochleate. 
     
     
         43 . The antifungal cochleate composition of  claim 31 , wherein the one or more of the cochleates comprises a lipid component, the lipid component comprising soy phosphatidylserine in an amount ranging from about 40%-70% by weight. 
     
     
         44 . The antifungal cochleate composition of  claim 31 , wherein the one or more of the cochleates comprises a lipid component, the lipid component comprising soy phosphatidylserine in an amount ranging from about 45%-55% by weight. 
     
     
         45 . The antifungal cochleate composition of  claim 31 , wherein the lipid component further comprises phosphatidylcholine. 
     
     
         46 . The antifungal cochleate composition of  claim 31 , wherein the one or more cochleates comprise a size-regulating agent. 
     
     
         47 . The antifungal cochleate composition of  claim 46 , wherein the size-regulating agent is a bile salt. 
     
     
         48 . The antifungal cochleate composition of  claim 46 , wherein the size-regulating agent comprises at least one of oxycholate, cholate, chenodeoxycholate, taurocholate, glycocholate, taurochenodeoxycholate, glycochenodeoxycholate, deoxycholate, and/or lithocholate. 
     
     
         49 . The antifungal cochleate composition of  claim 31 , wherein the one or more cochleates comprises an aggregation inhibitor.