Cyclodextrin compositions encapsulating a selective atp inhibitor and uses thereof

Abstract

The invention provides compositions comprising cyclodextrins encapsulating a selective ATP inhibitor, as well as uses thereof.

1 . A composition comprising a cyclodextrin and a pharmaceutical agent represented in the general formula: 
       
         
           
           
               
               
           
         
         wherein, independently of each occurrence:
 X represents a halide, a sulfonate, a carboxylate, an alkoxide, or an amine oxide; 
 R 1  represents OR, H, N(R″) 2 , C1-C6 alkyl, C6-C12 aryl, C1-C6 heteroalkyl, or C6-C12 heteroaryl; 
 R″ represents H, C1-C6 alkyl, or C6-C12 aryl; 
 R represents H, alkali metal, C1-C6 alkyl, C6-C12 aryl or C(O)R′; and 
 R′ represents H, C1-C20 alkyl or C6-C12 aryl, 
 
         wherein the cyclodextrin encapsulates the pharmaceutical agent. 
       
     
     
         2 . The composition of  claim 1 , wherein at least one α-D-glucopyranoside unit of the cyclodextrin has at least one hydroxyl chemical group replaced with an ionizable chemical group. 
     
     
         3 . The composition of  claim 2 , wherein the at least one hydroxyl chemical group of the at least one α-D-glucopyranoside unit is selected from the group consisting of C2, C3, and C6 hydroxyl chemical groups, wherein the C2, C3, and C6 hydroxyl chemical groups of at least one α-D-glucopyranoside unit of the cyclodextrin are replaced with ionizable chemical groups. 
     
     
         4 . (canceled) 
     
     
         5 . The composition of claim, wherein the at least one α-D-glucopyranoside unit of the cyclodextrin is selected from the group consisting of two, three, four, five, six, seven, eight, and all α-D-glucopyranoside units of the cyclodextrin. 
     
     
         6 . The composition of  claim 2 , wherein the ionizable chemical group is the same at all replaced positions. 
     
     
         7 - 9 . (canceled) 
     
     
         10 . The composition of  claim 3 , wherein the ionizable chemical groups are basic or acidic functional groups selected from the group consisting of amino, ethylene diamino, dimethyl ethylene diamino, dimethyl anilino, dimethyl naphthylamino, trimethyl amino, succinyl, carboxyl, carboxy methyl, carboxy ethyl, sulfonyl, sulphate, sulfobutyl, and phosphate functional groups. 
     
     
         11 . (canceled) 
     
     
         12 . The composition of  claim 1 , wherein the composition is a liquid or solid pharmaceutical formulation. 
     
     
         13 . The composition of  claim 1 , wherein the pharmaceutical agent is neutrally charged or hydrophobic. 
     
     
         14 . The composition of  claim 1 , wherein the cyclodextrin is selected from the group consisting of β-cyclodextrin, α-cyclodextrin, and γ-cyclodextrin. 
     
     
         15 . (canceled) 
     
     
         16 . The composition of  claim 1 , wherein the pharmaceutical agent is 3-halopyruvate. 
     
     
         17 . The composition of  claim 1 , wherein the pharmaceutical agent is 3-bromopyruvate. 
     
     
         18 . The composition of  claim 1 , wherein the composition is formulated for systemic administration. 
     
     
         19 . The composition of  claim 1 , further comprising an anti-cancer therapeutic agent. 
     
     
         20 . A kit comprising a composition of  claim 1 , and instructions for use. 
     
     
         21 . A method of treating a subject having a cancer comprising administering to the subject a therapeutically effective amount of a composition of  claim 1 . 
     
     
         22 . The method of  claim 21 , wherein the composition is administered systemically, wherein the systemic administration is selected from the group consisting of oral, intravenous, intraperitoneal, subcutaneous, and intramuscular administration. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 21 , wherein the subject is treated with at least one additional anti-cancer therapy, wherein the at least one additional anti-cancer therapy is radiation therapy. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 21 , wherein the cancer is a solid tumor. 
     
     
         27 . The method of  claim 21 , wherein the cancer is selected from the group consisting of liver cancer, pancreatic cancer, lung cancer and breast cancer. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 21 , wherein the subject is a mammal, wherein the mammal is a human. 
     
     
         30 . (canceled)