Active agents and their oligomers and polymers

Abstract

Conjugates comprising at least two active agents linked by a diglycolic acid or polyglycol diacid linker are disclosed. The invention also concerns oligomers and polymers of these conjugates and their use in therapeutic and industrial applications for localized, immediate or fast release delivery of an active agent, such as an anti-microbial, anti-infective, or antiseptic agent.

1 . A compound according to formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         each D is the same or different and is an active agent, such as a therapeutic agent, 
         R 1  is selected from the group consisting of —[(CH 2 ) x O] y (CH 2 ) z —, —(CH 2 ) y —, —[CH═CH—O] y (CH 2 ) z —, —[(CH═CH—CH 2 —O] y (CH 2 ) z —, —[CH 2 —CH═CH—O] y (CH 2 ) z —, —[(CH 2 ) x O] y (CH═CH)—,
 wherein w is 1 or 2, 
 x is 2 or 3, and 
 y is equal to an integer from 1 to 10, from 1 to 4, or from 1 to 3, 
 z is equal to 1 or 2, and 
 the carbon atoms of R 1  may be optionally substituted with substituents selected from the group consisting of C 1  to C 12  alkyl, C 1  to C 12  alkoxy, C 3  to C 12  cycloalkyl, C 3  to C 12  cycloalkoxy, C 1  to C 12  alkanoyl, C 1  to C 12  alkanoyloxy, C 1  to C 12  alkoxy carbonyl, C 1  to C 12  alkylthio, azido, cyano, nitro, fluoro, chloro, bromo, iodo, hydroxy, oxo, carboxy, aryl, aryloxy, heteroaryl, and heteroaryloxy; 
 
         each X is the same or different and is selected from the group consisting of —O—, —NR 2 —, —S—, —SO—, and —SO 2 —,
 wherein R 2  is an alkyl group of 1 to 12 carbon atoms. 
 
       
     
     
         2 . The compound of  claim 1 , wherein each D is independently selected from the group consisting of anti-inflammatory agents, anti-infective agents, antibacterial agents, antiseptic agents and antioxidants. 
     
     
         3 . The compound of  claim 2  having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 2  having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         5 . A compound comprising a unit of the formula (II): 
       
         
           
           
               
               
           
         
         wherein
 n is a positive integer; 
 p is 0 or 1; 
 
         each D is the same or different and is an active agent, such as a therapeutic agent, 
         R 1  is selected from the group consisting of —[(CH 2 ) x O] y (CH 2 ) z —, —(CH 2 ) y —, —[CH═CH—O] y (CH 2 ) z —, —[(CH═CH—CH 2 —O] y (CH 2 ) z —, —[CH 2 —CH═CH—O] y (CH 2 ) z —, —[(CH 2 ) x O] y (CH═CH)—,
 wherein w is 1 or 2, 
 x is 2 or 3, 
 y is equal to an integer from 1 to 10, from 1 to 4, or from 1 to 3, 
 z is equal to 1 or 2, and 
 the carbon atoms of R 1  may be optionally substituted with substituents selected from the group consisting of C 1  to C 12  alkyl, C 1  to C 12  alkoxy, C 3  to C 12  cycloalkyl, C 3  to C 12  cycloalkoxy, C 1  to C 12  alkanoyl, C 1  to C 12  alkanoyloxy, C 1  to C 12  alkoxy carbonyl, C 1  to C 12  alkylthio, azido, cyano, nitro, fluoro, chloro, bromo, iodo, hydroxy, oxo, carboxy, aryl, aryloxy, heteroaryl, and heteroaryloxy; 
 
         each X is the same or different and is selected from the group consisting of —O—, —NR 2 —, —S—, —SO—, and —SO 2 —,
 wherein R 2  is an alkyl group of 1 to 12 carbon atoms, when p is 0, n is not 1. 
 
       
     
     
         6 . The compound of  claim 5 , wherein n is an integer from 2 to 100. 
     
     
         7 . The compound of  claim 5 , wherein the unit of formula (II) comprises 
       
         
           
           
               
               
           
         
         wherein n is a positive integer greater than 1 and wherein R 3  is selected from the group consisting of —H, —CF 3 , —F, —Cl, —Br, —I, —OH, —NH 2 , —NO 2 , —CN, C 1  to C 12  straight-chain or branched alkyl, C 1  to C 12  alkoxy, C 3  to C 12  cycloalkyl, C 3  to C 12  cycloalkoxy, C 1  to C 12  alkanoyl, C 1  to C 12  alkanoyloxy, C 1  to C 12  alkoxy carbonyl, C 1  to C 12  alkylthio, azido, oxo, carboxy, aryl, aryloxy, heteroaryl, heteroaryloxy, and the following structures: 
       
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 7 , wherein R 3  is —H. 
     
     
         9 . The compound of  claim 7 , wherein R 3  is 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 5 , wherein the unit of formula (II) comprises 
       
         
           
           
               
               
           
         
         wherein n is a positive integer greater than 1 and wherein R 3  is selected from the group consisting of —H, —CF 3 , —F, —Cl, —Br, —I, —OH, —NH 2 , —NO 2 , —CN, C 1  to C 12  straight-chain or branched alkyl, C 1  to C 12  alkoxy, C 3  to C 12  cycloalkyl, C 3  to C 12  cycloalkoxy, C 1  to C 12  alkanoyl, C 1  to C 12  alkanoyloxy, C 1  to C 12  alkoxy carbonyl, C 1  to C 12  alkylthio, azido, oxo, carboxy, aryl, aryloxy, heteroaryl, heteroaryloxy, and the following structures: 
       
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 10 , wherein R 3  is —H. 
     
     
         12 . The compound of  claim 10 , wherein R 3  is 
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound of  claim 8 , wherein n is equal to an integer from 2 to 10. 
     
     
         14 . The compound of  claim 8 , wherein n is equal to 3. 
     
     
         15 . The compound of  claim 5 , wherein each D is independently selected from the group consisting of anti-inflammatory agents, anti-infective agents, antibacterial agents, antiseptic agents and antioxidants. 
     
     
         16 . A composition comprising an effective amount of the compound of  claim 1  and a suitable vehicle. 
     
     
         17 . A method for treating conditions of the hair, skin or scalp of a mammal comprising administering the composition of  claim 16  to a mammal. 
     
     
         18 . A composition comprising an effective amount of the compound of  claim 5  and a suitable vehicle. 
     
     
         19 . A method for treating conditions of the hair, skin or scalp of a mammal comprising administering the composition of  claim 18  to a mammal. 
     
     
         20 . A topical composition comprising a surfactant and a therapeutically effective amount of a compound having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         21 . A method for treating conditions of the hair, skin or scalp of a mammal comprising administering the composition of  claim 20  to a mammal. 
     
     
         22 . A device coated with or comprised of the compound of  claim 1 . 
     
     
         23 . A method for inhibiting mold, bacteria or biofilm formation on a surface comprising applying an effective amount of the compound of  claim 1  to the surface or admixing an effective amount of the compound of  claim 1  with the surface as it is formed. 
     
     
         24 . A device coated with or comprised of the compound of  claim 5 . 
     
     
         25 . A method for inhibiting mold, bacteria or biofilm formation on a surface comprising applying an effective amount of the compound of  claim 5  to the surface or admixing an effective amount of the compound of  claim 5  with the surface as it is formed. 
     
     
         26 . A polyanhydride comprising a compound of formula (III): 
       
         
           
           
               
               
           
         
         wherein
 n is a positive integer; 
 p is the same or different and is 0 or 1; 
 
         each D is the same or different and is an active agent, such as a therapeutic agent, 
         R 1  is the same or different and is selected from the group consisting of
 —[(CH 2 ) x O] y (CH 2 ) z —, —(CH 2 ) y —, —[CH═CH—O] y (CH 2 ) z —, —[(CH═CH—CH 2 —O] y (CH 2 ) z —, —[CH 2 —CH═CH—O] y (CH 2 ) z —, —[(CH 2 ) x O] y (CH═CH)—, 
 
         preferably —(CH 2 CH 2 O) y (CH 2 ) z — or —(CH 2 )—
 wherein w is 1 or 2, 
 x is 2 or 3, 
 y is equal to an integer from 1 to 10, from 1 to 4, or from 1 to 3, 
 z is 1 or 2, and 
 the carbon atoms of R 1  may be optionally substituted with substituents selected from the group consisting of C 1  to C 12  alkyl, C 1  to C 12  alkoxy, C 3  to C 12  cycloalkyl, C 3  to C 12  cycloalkoxy, C 1  to C 12  alkanoyl, C 1  to C 12  alkanoyloxy, C 1  to C 12  alkoxy carbonyl, C 1  to C 12  alkylthio, azido, cyano, nitro, halo, hydroxy, oxo, carboxy, aryl, aryloxy, heteroaryl, and heteroaryloxy; 
 
         each X is independently selected from the group consisting of —O—, —NR 2 —, —S—, 
         —SO—, and —SO 2 —, 
         wherein R 2  is an alkyl group of 1 to 12 carbon atoms. 
       
     
     
         27 . The polyanhydride of  claim 26  of the formula: 
       
         
           
           
               
               
           
         
       
       wherein n is a positive integer greater than 1. 
     
     
         28 . The polyanhydride of  claim 26  of the formula: 
       
         
           
           
               
               
           
         
       
       wherein n is a positive integer greater than 1.