Conjugates of biologically active compounds, methods for their preparation and use, formulation and pharmaceutical applications thereof

Abstract

This invention features a method of identifying a compound useful for enhancing efficacy of a therapeutic agent. The method includes incubating a compound in blood cells; separating immune cells from erythrocytic cells; and determining the ratio of the concentration of the compound in the immune cells to the concentration of the compound in the erythrocytic cells; wherein the compound comprises a transportophore and a therapeutic agent, in which the transportophore is covalently bonded to the therapeutic agent via a bond or a linker.

1 . A method of identifying a compound useful for enhancing efficacy of a therapeutic agent, comprising
 incubating a compound in blood cells,   separating immune cells from erythrocytic cells, and   determining the ratio of the concentration of the compound in the immune cells to the concentration of the compound in the erythrocytic cells,   wherein the compound comprises a transportophore and a therapeutic agent, in which the transportophore is covalently bonded to the therapeutic agent via a bond or a linker.   
     
     
         2 . The method of  claim 1 , the compound has the following formula:
   TL-C) m ,   wherein   T is a transportophore,   L is a bond or a linker having a molecular weight up to 240 dalton,   C is a non-antibiotic therapeutic agent, and   m is 1, 2, 3, 4, 5, 6, 7, or 8,   in which the transportophore has an immune selectivity ratio of at least 2, the transportophore is covalently bonded to the non-antibiotic therapeutic agent via the bond or the linker, and the compound has an immune selectivity ratio of at least 2.   
     
     
         3 . The method of  claim 1 , wherein the separating is by density gradient centrifugation. 
     
     
         4 . The method of  claim 1 , wherein the determining is by fluorescence microscopy. 
     
     
         5 . The method of  claim 1 , wherein the determining is by liquid chromatography. 
     
     
         6 . The method of  claim 1 , wherein the therapeutic agent is an anti-inflammatory agent. 
     
     
         7 . The method of  claim 1 , wherein the therapeutic agent is an anti-infectious agent. 
     
     
         8 . The method of  claim 1 , wherein the therapeutic agent is an anti-cancer agent. 
     
     
         9 . The method of  claim 1 , wherein the therapeutic agent is an allergy-suppressive agent. 
     
     
         10 . The method of  claim 1 , wherein the therapeutic agent is an immune-suppressant agent. 
     
     
         11 . The method of  claim 1 , wherein the therapeutic agent is an agent for treating a hematopoietic disorder. 
     
     
         12 . The method of  claim 1 , wherein the therapeutic agent is an agent for treating a metabolic disease. 
     
     
         13 . A method for delivering a therapeutic agent with a selective concentration, comprising:
 identifying a compound by a method of  claim 1 , and   delivering the compound to a cell,   wherein the compound comprises a transportophore and a therapeutic agent, in which the transportophore is covalently bonded to the therapeutic agent via a bond or a linker.   
     
     
         14 . The method of  claim 13 , wherein the cell is a cell of respiratory tissue. 
     
     
         15 . The method of  claim 13 , wherein the cell is a cell of neoplastic tissue. 
     
     
         16 . The method of  claim 13 , wherein the cell is a cell mediating allergic responses. 
     
     
         17 . A cell comprising a therapeutic agent identified by the method  claim 1 . 
     
     
         18 . A cell comprising a therapeutic agent identified by the method  claim 2 .