Biodegradable elastomers prepared by the condensation of an organic di-, tri- or tetra-carboxylic acid and an organic diol

Abstract

The present disclosure relates to biodegradable and biocompatible elastomeric polymers prepared by the condensation of an organic di-, tri- or tetra-carboxylic acid and an organic diol followed by thermal crosslinking with a bis- or tri-lactone or reaction with a photosensitive compound and subsequent photocrosslinking. Said elastomers are amorphous, have a glass transition temperature below both room temperature and body temperature and will homogeneously degrade to water soluble by-products with no reported toxicity.

1 . A polymer comprising:
 a copolymer, the copolymer comprising polymerizing units of:   a) about 1 to about 99% by weight of, based on the total mass of the copolymer, at least one of a monomer of the formula I, II, III or IV   
       
         
           
           
               
               
           
         
       
       in which R 1 , R 2  and R 3  are independently C 3 -C 20 cycloalkylene, C 1 -C 30 alkylene, C 2 -C 30 alkenylene, or C 2 -C 30 alkynylene, said latter 3 groups being straight-chained or branched and/or interrupted by one, two or three C 3 -C 10  cyclic moieties therein, and said 4 groups being optionally substituted by one or more groups selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl;
 b) about 1 to about 99%, by weight, based on the total mass of the copolymer, of a monomer of the formula V,
   HO—R 5 —OH  (V) 
 
 in which the radical R 5  is C 3 -C 20 cycloalkylene, C 1 -C 30 alkylene, C 2 -C 30 alkenylene, C 1- alkynylene, said latter 3 groups being straight-chained or branched and/or interrupted by one, two or three C 3 -C 10  cyclic moieties therein, wherein one or more of the carbon atoms may be replaced by oxygen, and said 4 groups being optionally substituted by one or more groups selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl; 
 or R 5  is a polyalkylene glycol or a poly-ε-caprolactone; 
 and wherein the copolymer is crosslinked with 
 c) about 0.5 to about 50% by weight of the total polymer, of a crosslinker of the formula VI or VII 
 
       
         
           
           
               
               
           
         
         wherein R 6  and R 7  are independently OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl; 
         n is an integer from 1 to 20; and 
         m is an integer from 0 to 20, 
         and wherein any of the lactone rings are optionally substituted by one or more substituents selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl. 
       
     
     
         2 . The polymer according to  claim 1 , wherein R 1 , R 2  and R 3  are independently C 3 -C 10 cycloalkylene, C 1 -C 10 alkylene, C 2 -C 10 alkenylene, or C 2 -C 10 alkynylene, said latter 3 groups being straight-chained or branched and/or interrupted by one, two or three C 3 -C 6  cyclic moieties therein, and said 4 groups being optionally substituted by one to six groups selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl. 
     
     
         3 . The polymer according to  claim 1 , wherein the monomer of formula I, II, III or IV is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         4 . (canceled) 
     
     
         5 . The polymer according to  claim 1 , wherein R 5  is C 3 -C 10 cycloalkylene, C 1 -C 10 alkylene, C 2 -C 10 alkenylene, C 2 -C 10 alkynylene, said latter 3 groups being straight-chained or branched and/or interrupted by one, two or three C 3 -C 6  cyclic moieties therein, wherein one or more of the carbon atoms may be replaced by oxygen, and said 4 groups being optionally substituted by one to six groups selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl. 
     
     
         6 . The polymer according to  claim 5 , wherein the monomer of formula V is selected from, 
       
         
           
           
               
               
           
         
       
     
     
         7 . The polymer according to  claim 1 , wherein the monomer of formula V is polyethylene glycol, polypropylene glycol or a poly-ε-caprolactone. 
     
     
         8 - 15 . (canceled) 
     
     
         16 . The polymer according to  claim 1 , wherein R 6  and R 7  are C 1 -C 6 alkyl. 
     
     
         17 . (canceled) 
     
     
         18 . The polymer according to  claim 1 , wherein the crosslinker of the formula VI is 
       
         
           
           
               
               
           
         
       
     
     
         19 . A polymer comprising:
 a copolymer, the copolymer comprising polymerizing units of:   a) about 1 to about 99% by weight of, based on the total mass of the copolymer, at least one of a monomer of the formula I, II, III or IV   
       
         
           
           
               
               
           
         
         in which R 1 , R 2  and R 3  are independently C 3 -C 20 cycloalkylene, C 1 -C 30 alkylene, C 2 -C 30 alkenylene, or C 2 -C 30 alkynylene, said latter 3 groups being straight-chained or branched and/or interrupted by one, two or three C 3 -C 10  cyclic moieties therein, and said 4 groups being optionally substituted by one or more groups selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl; 
         b) about 1 to about 99%, by weight, based on the total mass of the copolymer, of a monomer of the formula V,
   HO—R 5 —OH  (V) 
 
         in which the radical R 5  is C 3 -C 20 cycloalkylene, C 1 -C 30 alkylene, C 2 -C 30 alkenylene, C 2 -C 30 alkynylene, said latter 3 groups being straight-chained or branched and/or interrupted by one, two or three C 3 -C 10  cyclic moieties therein, wherein one or more of the carbon atoms may be replaced by oxygen, and said 4 groups being optionally substituted by one or more groups selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl;
 or R 5  is a polyalkylene glycol or a poly-ε-caprolactone; 
 
         and wherein free hydroxyl groups or carboxyl groups of the copolymer are derivatized with a photosensitive compound and are photochemically crosslinked. 
       
     
     
         20 . The polymer according to  claim 19 , wherein R 1 , R 2  and R 3  are independently C 3 -C 10 cycloalkylene, C 1 -C 10 alkylene, C 2 -C 10 alkenylene, or C 2 -C 10 alkynylene, said latter 3 groups being straight-chained or branched and/or interrupted by one, two or three C 3 -C 6  cyclic moieties therein, and said 4 groups being optionally substituted by one to six groups selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl. 
     
     
         21 . The polymer according to  claim 19 , wherein the monomer of formula I, II, III or IV is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         22 . The polymer according to  claim 19 , wherein the monomer of formula I, II, III or IV is selected from 
       
         
           
           
               
               
           
         
       
     
     
         23 . The polymer according to  claim 19 , wherein R 5  is C 3 -C 10 cycloalkylene, C 1 -C 10 alkylene, C 2 -C 10 alkenylene, C 2 -C 10 alkynylene, said latter 3 groups being straight-chained or branched and/or interrupted by one, two or three C 3 -C 6  cyclic moieties therein, wherein one or more of the carbon atoms may be replaced by oxygen, and said 4 groups being optionally substituted by one to six groups selected from OH, halo, OR 4  or R 4 , in which R 4  is selected from C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 6 cycloalkyl. 
     
     
         24 . The polymer according to  claim 23 , wherein the monomer of formula V is selected from, 
       
         
           
           
               
               
           
         
       
     
     
         25 . The polymer according to  claim 24 , wherein the monomer of formula V is polyethylene glycol, polypropylene glycol or a poly-ε-caprolactone. 
     
     
         26 - 29 . (canceled) 
     
     
         30 . A biodegradable and biocompatible elastomeric polymer comprising a condensation polymer of an organic di-, tri- or tetra-carboxylic acid and an organic diol, said condensation polymer being either
 (a) thermally crosslinked with a bis- or tri-lactone; or   (b) reacted with a photosensitive compound to form a photosensitive condensation polymer which is photocrosslinked, to provide the biodegradable and biocompatible elastomeric polymer.   
     
     
         31 . The biodegradable and biocompatible elastomeric polymer according to  claim 30 , wherein the organic di-, tri- or tetra-carboxylic acid is of a natural origin and degrades to non-toxic by-products. 
     
     
         32 . The biodegradable and biocompatible elastomeric polymer according to  claim 31 , wherein the organic di-, tri- or tetra-carboxylic acid comprises saturated or unsaturated alkyl or cycloalkyl groups. 
     
     
         33 . (canceled) 
     
     
         34 . The biodegradable and biocompatible elastomeric polymer according to  claim 33 , wherein the organic di-, tri- or tetra-carboxylic acid is mesaconic acid, tartaric acid, aconitic acid, tricarballylic acid, malic acid, trans-aconitic acid, citric acid, agaric acid, citraconic acid, fumaric acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, glutaric acid, oxalic acid, 1,1,12,12-dodecanetetracarboxylic acid, 1,2,3,4-butanetetracarboxylic acid, cyclobutane-1,2,3,4-tetracarboxylic acid, meso-butane-1,2,3,4-tetracarboxylic acid, 1,1,2,3-propanetetracarboxylic acid or 1,1,3,3-propanetetracarboxylic acid. 
     
     
         35 . (canceled) 
     
     
         36 . The biodegradable and biocompatible elastomeric polymer according to  claim 30 , wherein the organic diol comprises saturated or unsaturated alkyl groups or cycloalkyl groups. 
     
     
         37 . The biodegradable and biocompatible elastomeric polymer according to  claim 36 , wherein the alkyl or cycloalkyl group comprises between 2 and 30 carbon atoms. 
     
     
         38 . (canceled) 
     
     
         39 . The biodegradable and biocompatible elastomeric polymer according to  claim 38 , wherein the organic diol is 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, 1,10-decandiol or 1,12-dodecandiol. 
     
     
         40 . (canceled) 
     
     
         41 . The biodegradable and biocompatible elastomeric polymer according to  claim 30 , wherein the organic diol is a polyethylene glycol or a polypropylene glycol. 
     
     
         42 - 43 . (canceled) 
     
     
         44 . The biodegradable and biocompatible elastomeric polymer according to  claim 30 , wherein the condensation polymer is thermally crosslinked with a bis- or tri-lactone. 
     
     
         45 . The biodegradable and biocompatible elastomeric polymer according to  claim 44 , wherein the bis- or tri-lactone comprises between 7 and 18 member rings. 
     
     
         46 . (canceled) 
     
     
         47 . The biodegradable and biocompatible elastomeric polymer according to  claim 46 , wherein the bis- or tri-lactone comprises bis-ε-caprolactone. 
     
     
         48 - 52 . (canceled) 
     
     
         53 . The biodegradable and biocompatible elastomeric polymer according to  claim 30 , wherein the photosensitive compound is acrolyl chloride or an acrylate derivative, coumarin or a coumarin-derivative, a cinnamate or a cinnamate derivative. 
     
     
         54 - 60 . (canceled) 
     
     
         61 . The biodegradable and biocompatible elastomeric polymer according to  claim 30 , wherein the photosensitive condensation polymer is photocrosslinked upon exposure to UV or laser light. 
     
     
         62 . The biodegradable and biocompatible elastomeric polymer according to  claim 61 , wherein the UV or laser light has a wavelength of between about 200 to 700 nm. 
     
     
         63 . (canceled) 
     
     
         64 . The biodegradable and biocompatible elastomeric polymer according to  claim 30 , wherein the photosensitive condensation polymer is photocrosslinked upon exposure to visible light. 
     
     
         65 . The biodegradable and biocompatible elastomeric polymer according to  claim 64 , wherein the visible light has a wavelength of about 380 nm to about 750 nm. 
     
     
         66 - 72 . (canceled) 
     
     
         73 . The biodegradable and biocompatible elastomeric polymer according to  claim 30  having a glass transition temperature (T g ) below 0° C. 
     
     
         74 . The biodegradable and biocompatible elastomeric polymer according to  claim 73  having a glass transition temperature (T g ) from between about 0° C. to −15° C. 
     
     
         75 - 106 . (canceled)