Polyesters, Methods of Making Polyesters and Uses Therefor

Abstract

Polyester compositions and functionalized polyester compositions are provided along with methods of making the compositions as well as methods of using the compositions, for example as a tissue engineering bioscaffold and as a drug-delivery vehicle.

1 - 77 . (canceled) 
     
     
         78 . A method of making a polymer composition, comprising polymerizing a first compound having either one or two cyclic ether groups having the structure 
       
         
           
           
               
               
           
         
       
       in which n is 1-4 and no additional reactive groups, with a second compound that is the same or different from the first compound, comprising one or two carboxyl groups and no additional reactive groups, wherein if the first compound has only one cyclic ether group, then it also comprises a carboxyl group and the second compound comprises a cyclic ether group having the structure 
       
         
           
           
               
               
           
         
       
       in which n is 1-4. 
     
     
         79 . The method of  claim 78 , comprising polymerizing either
 a. a compound having the structure A-B-A′ with a compound having the structure HOC(O)—B′—C(O)OH, where A and A′ are cyclic ethers having the structure   
       
         
           
           
               
               
           
         
       
       in which n is 1-4 and A and A′ can be the same or different and B and B′ are non-reactive organic groups, and B and B′ can be the same or different or B′ is not present, to produce a polyester; or
 b. a compound having the structure A-B—C(O)OH with a compound having the structure A′-B′—C(O)OH that is the same or different than A-B—C(O)OH, where A and A′ are cyclic ethers having the structure 
 
       
         
           
           
               
               
           
         
       
       in which n is 1-4 and A and A′ can be the same or different, and B and B′ are non-reactive organic groups without strong nucleophilicity and B and B′ can be the same or different, to produce a polyester. 
     
     
         80 . The method of  claim 79 , in which one or both of B and B′ are C 8  alkyl groups, aliphatic alkyl groups, saturated alkyl groups, saturated straight-chain alkyl groups, selected from the group consisting of: —O(O)C—(CH 2 ) 8 —C(O)O—, —CH═CH—, —CH 2 —CH 2 —, phenyl, —O—CH 2 —CH 2 —O—, —O—CH═CH—O—, —O(O)C—CH═CH—C(O)O—, —O(O)C-phenyl-C(O)O—, —O(O)C-cyclohexy-C(O)O—, and —CH(OH)—CH(OH)—, —O(O)C—C(NHY)—CH 2 —C(O)O— where Y is a protective group, and —O(O)C—C(NHY)—CH 2 —CH 2 —C(O)O where Y is a protective group. 
     
     
         81 . The method of  claim 79 , comprising reacting diglycidyl sebacate with sebacic acid (HOC(O)—(CH 2 ) 8 —C(O)OH). 
     
     
         82 . The method of  claim 78 , in which the polymerization is conducted in the presence of one or more nucleophilic functional groups. 
     
     
         83 . The method of  claim 78 , in which the polymerization is conducted in the presence of one or more of bis(tetrabutylammonium) sebacate, tetrabutylammonium bromide, tetrabutylammonium fluoride, tetrabutylammonium iodide, tetraphenylphosphonium chloride, tetramethylphosphonium iodide, sodium methoxide, lithium acetate, and sodium sulfide. 
     
     
         84 . The method of  claim 78 , in which the compound A-B-A′ is prepared by direct esterification of glycidol with a compound XOC(O)—(CH 2 ) 8 —C(O)OX′ in which X and X′ are independently halide. 
     
     
         85 . The method of  claim 78 , further comprising functionalizing a pendant —OH of the polyester. 
     
     
         86 . The method of  claim 85 , wherein the pendant OH is functionalized:
 with one or more protected amino acids or a peptide;   with a peptide selected from the group consisting of Ile-Lys-Val-Ala-Val (IKVAV) (SEQ ID NO: 1), Arg-Gly-Asp (RGD), Arg-Gly-Asp-Ser (RGDS) (SEQ ID NO: 2), Ala-Gly-Asp (AGD), Lys-Gln-Ala-Gly-Asp-Val (KQAGDV) (SEQ ID NO: 3), Val-Ala-Pro-Gly-Val-Gly (VAPGVG) (SEQ ID NO: 4), APGVGV (SEQ ID NO: 5), PGVGVA (SEQ ID NO: 6), VAP, GVGVA (SEQ ID NO: 7), VAPG (SEQ ID NO: 8), VGVAPG (SEQ ID NO: 9), VGVA (SEQ ID NO: 10), VAPGV (SEQ ID NO: 11) and GVAPGV (SEQ ID NO: 12);   with an acetylcholine group   
       
         
           
           
               
               
           
         
         to produce a reversibly photo-crosslinkable polymer network; 
         by a reaction with a dicarboxylic acid selected from maleic acid or succinic acid; 
         by reaction with a compound that carries positive charge to produce a polycation; or 
         with a negatively-charged compound. 
       
     
     
         87 . The method of  claim 85 , wherein the pendant OH group is functionalized by reaction with a compound that carries a positive charge to produce a polycation, further comprising binding a polyanion to the polycation. 
     
     
         88 . The method of  claim 87 , further comprising binding the polycation, and the polyanion to a growth factor to produce a ternary complex. 
     
     
         89 . The method of  claim 78 , further comprising curing the polyester in the presence of a compound comprising two or more groups reactive with the polyester. 
     
     
         90 . The method of  claim 79 , in which one or both of B and B′ comprise a blocked amino group. 
     
     
         91 . The method of  claim 90 , comprising polymerizing a compound having the structure A-B-A′ with a compound having the structure HOC(O)—B′—C(O)OH, where A and A′ are cyclic ethers having the structure 
       
         
           
           
               
               
           
         
       
       which n is 1-4 and A and A′ can be the same or different and B and B′ are non-reactive organic groups, and B and B′ can be the same or different or B′ is not present, to produce a polyester, and in which HOC(O)—B′—C(O)OH is one of blocked aspartic acid and blocked glutamic acid. 
     
     
         92 . The method of  claim 90 , further comprising reacting the blocked amino group with an NH 2 -reactive cationic compound to produce a polycation. 
     
     
         93 . The method of  claim 92  further comprising binding a polyanion to the polycation, wherein the polyanion is one of heparin or heparin sulfate. 
     
     
         94 . The method of  claim 93 , further comprising binding the polycation to a growth factor to produce a ternary complex. 
     
     
         95 . The method of  claim 85 , wherein the pendant OH group is functionalized with a negatively-charged compound, further comprising calcifying the negatively-charged functional groups with Ca 2+ , and wherein the Ca 2+  is reacted with phosphate to produce a calcium phosphate derivatized polymer composition. 
     
     
         96 . A biological scaffold or drug delivery vehicle comprising a polymer composition according to  claim 98 . 
     
     
         97 . A photolithography method comprising depositing onto a substrate a polymer composition prepared according to  claim 86  in which the pendant OH is functionalized to produce a reversibly photo-crosslinkable polymer network; and either
 a. exposing the polymer-coated surface to ultraviolet light at a wavelength for cross-linking the polymer composition in a pattern and removing non-polymerized polymer, or 
 b. exposing the polymer-coated surface to ultraviolet light at a wavelength for cross-linking the polymer composition, and exposing a portion of the cross-linked polymer-coated surface to ultraviolet light at a wavelength for cleaving the photo-cross-linked polymer. 
 
     
     
         98 . A polymer composition comprising the structure [—OC(O)—B′—CH(OR1)-B—] n  or —[OC(O)—B—C(O)O—CH 2 —CH(O—R1)-CH 2 —B′—CH 2 —CH(O—R2)-CH 2 —] n , in which B and B′ are the same or different and are organic groups, or B′ is not present, and R1 and R2 are the same or different and are hydrogen or a functional group. 
     
     
         99 . The composition of  claim 98  in which R1 and R2 are:
 a. independently groups comprising 
 
       
         
           
           
               
               
           
         
       
       a carboxy-containing group, an α, β unsaturated carboxylic acid; an amine-containing group, a quaternary ammonium containing group, maleic acid, a peptide; maleate; succinate or phosphate, halo-containing groups;
 b. charged; or 
 c. independently, a peptide selected from the group consisting of Ile-Lys-Val-Ala-Val (IKVAV) (SEQ ID NO: 1), Arg-Gly-Asp (RGD), Arg-Gly-Asp-Ser (RGDS) (SEQ ID NO: 2), Ala-Gly-Asp (AGD), Lys-Gln-Ala-Gly-Asp-Val (KQAGDV) (SEQ ID NO: 3), Val-Ala-Pro-Gly-Val-Gly (VAPGVG) (SEQ ID NO: 4), APGVGV (SEQ ID NO: 5), PGVGVA (SEQ ID NO: 6), VAP, GVGVA (SEQ ID NO: 7), VAPG (SEQ ID NO: 8), VGVAPG (SEQ ID NO: 9), VGVA (SEQ ID NO: 10), VAPGV (SEQ ID NO: 11) and GVAPGV (SEQ ID NO: 12). 
 
     
     
         100 . The composition of  claim 98 , attached non-covalently to a calcium phosphate. 
     
     
         101 . The composition of  claim 98 , comprising poly(sebacoyl diglyceride) (PSeD) or functionalized PSeD. 
     
     
         102 . The composition of  claim 98  comprising phosphate derivatized PSeD.