Hydrolysable linkers and cross-linkers for absorbable polymers

Abstract

The present invention relates to the discovery of new class of linear and multiarmed hydrolysable linkers and cross linkers for use in the synthesis of biodegradable polymers such as, polyesters, polyurethanes, polyamides, polyureas and degradable epoxy amine resin. The linear and multiarmed hydrolysable linkers of the present invention include symmetrical and/or unsymmetrical ether carboxylic acids, amines, amide diols, amine polyols and isocyanates.

1 . A compound of Formula C, XIII, XIV, XV, or XVI: 
       
         
           
           
               
               
           
         
       
       wherein: 
       R is independently a C 1-25  alkylene diradical, wherein from 1-4 of the CH 2  groups within the alkyl chain are optionally independently replaced by O or S atoms, such that each of said O or S atoms is attached only to carbon atoms in the alkyl chain, with the proviso that multiple heteroatoms must be separated from each other and from the diradical chain ends by at least one carbon atom; 
       each a is independently an integer from 1 to 6; 
       alternatively, in formula XIII, XIV, XV, or XVI, each a is independently 0; 
       each b is independently an integer from 1 to 6; 
       each X is independently:
 —OC(═O)CH 2 — (inverse glycolic acid moiety), 
 —OC(═O)CH(CH 3 )— (inverse lactic acid moiety), 
 —OC(═O)CH 2 OCH 2 CH 2 — (inverse dioxanone acid moiety), 
 —OC(═O)CH 2 CH 2 CH 2 CH 2 CH 2 — (inverse caprolactone acid moiety), 
 —OC(═O)(CH 2 ) y —, or 
 —OC(═O)CH 2 (OCH 2 CH 2 ) z —; 
 
       each X 1  is independently:
 —CH 2 C(═O)O— (glycolic acid moiety), 
 —CH(CH 3 )C(═O)O— (lactic acid moiety), 
 —CH 2 CH 2 OCH 2 C(═O)O— (dioxanone acid moiety), 
 —CH 2 CH 2 CH 2 CH 2 CH 2 C(═O)O— (caprolactone acid moiety), 
 —(CH 2 ) y C(═O)O—, or 
 —(CH 2 CH 2 O) z CH 2 C(═O)O—; 
 
       each Y is independently:
 —OCH 2 C(═O)— (inverse glycolic ester moiety), 
 —OCH(CH 3 )C(═O)— (inverse lactic ester moiety), 
 —OCH 2 CH 2 OCH 2 C(═O)— (inverse dioxanone ester moiety), 
 —OCH 2 CH 2 CH 2 CH 2 CH 2 C(═O)— (inverse caprolactone ester moiety), 
 —O(CH 2 ) m C(═O)—, or 
 —O(CH 2 CH 2 O) n OCH 2 C(═O)—; 
 
       each Y 1  is independently:
 —C(═O)CH 2 O— (glycolic ester moiety), 
 —C(═O)CH(CH 3 )O— (lactic ester moiety), 
 —C(═O)CH 2 OCH 2 CH 2 O— (dioxanone ester moiety), 
 —C(═O)CH 2 CH 2 CH 2 CH 2 CH 2 O— (caprolactone ester moiety), 
 —C(═O)(CH 2 ) m O—, or 
 —C(═O)CH 2 O(CH 2 CH 2 O) n —; and 
 
       each m and n is independently an integer selected from 2 to 24. 
     
     
         2 . The compound of  claim 1 ,
 wherein:   
       each X is independently:
 —OC(═O)CH 2 —, —OC(═O)CH(CH 3 )—, —OC(═O)CH 2 OCH 2 CH 2 —, 
 
       or —OC(═O)CH 2 CH 2 CH 2 CH 2 CH 2 —; 
       each X 1  is independently:
 —CH 2 C(═O)O—, —CH(CH 3 )C(═O)O—, —CH 2 CH 2 OCH 2 C(═O)O—, 
 
       or —CH 2 CH 2 CH 2 CH 2 CH 2 C(═O)O—, 
       each Y is independently: —OCH 2 C(═O)—, —OCH(CH 3 )C(═O)—, —OCH 2 CH 2 OCH 2 C(═O)—, or —OCH 2 CH 2 CH 2 CH 2 CH 2 C(═O)— 
       each Y 1  is independently: —C(═O)CH 2 O—, —C(═O)CH(CH 3 )O—, —C(═O)CH 2 OCH 2 CH 2 O—, or —C(═O)CH 2 CH 2 CH 2 CH 2 CH 2 O—. 
     
     
         3 . The compound of  claim 2 ,
 wherein:   
       each X is independently: —OC(═O)CH 2 — or —OC(═O)CH(CH 3 )—; 
       each X 1  is independently: —CH 2 C(═O)O— or —CH(CH 3 )C(═O)O—; 
       each Y is independently: —OCH 2 C(═O)— or —OCH(CH 3 )C(═O)—; 
       each Y 1  is independently: —C(═O)CH 2 O— or —C(═O)CH(CH 3 )O—. 
     
     
         4 . The compound of  claim 1 , wherein the compound is a diacid of the structure: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound of  claim 1 , wherein the compound is a diacid of the structure: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1 , wherein the compound is a diacid of the structure: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 1 , wherein the compound is of the structure: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 1 , wherein the compound is of the structure: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 1 , wherein the compound is a diisocyanate of the structure: