Poly(orthoester) polymers, and methods of making and using same

Abstract

Poly(orthoester) polymers, and methods of making and using such poly(orthoester) polymers are provided. The poly(orthoester) polymers can be useful for applications including, for example, medical devices and pharmaceutical compositions. In a preferred embodiment, the poly(orthoester) polymers are biodegradable.

1 - 37 . (canceled) 
     
     
         38 . A method of preparing a polymer comprising combining components comprising at least one hydroxy-containing compound of the formula (Formula I) HO-A-OH and at least one ketene acetal under conditions effective to polymerize at least a portion of the at least one ketene acetal, wherein the at least one ketene acetal is selected from the group consisting of:
 a compound of the formula (Formula IV)   
       
         
           
           
               
               
           
         
         a compound of the formula (Formula V) 
       
       
         
           
           
               
               
           
         
       
       and combinations thereof; 
       wherein:
 each R 9  and R 17  independently represents hydrogen or an organic group; 
 each R 11 , R 13 , R 15 , and R 16  independently represents an organic group; 
 R 18  represents oxygen or an organic group and p=0 or 1; 
 each R 11  can optionally be joined with R 13  to form one or more rings; 
 geminal R 15  and R 16  groups can optionally be joined to each other to form rings; 
 each A is selected from the group consisting of —C(R 1 )(R 2 )—(C(R 5 ) 2 ) r —C(R 3 )(R 4 )—, —Ar het —, —Ar 1 C(R 6 )(R 7 )—, a group of the formula (Formula III) —Ar 2 —C(R 8 ) 2 —Ar 2 —(B) m —, and combinations thereof; 
 each R 1 , R 2 , R 3 , R 4 , and R 5  independently represents hydrogen or an organic group, r is 0 to 20, and one or more of R 1 , R 2 , R 3 , R 4 , and R 5  can optionally be joined with one another to form one or more rings, with the proviso that at least one of R 1 , R 2 , R 3 , and R 4  is selected from the group consisting of an ester-containing group, an amide-containing group, a nitrile-containing group, an ether-containing group, and combinations thereof; 
 Ar het  represents a 1,2-heteroarylene group; 
 Ar 1  represents a 1,2- or a 1,3-arylene group, or a 1,2- or a 1,3-heteroarylene group, R 6  and R 7  independently represent hydrogen or an organic group, and R 6  and/or R 7  can optionally be joined with each other or with the Ar 1  group to form one or more rings; and 
 each Ar 2  independently represents an arylene group, each R 8  independently represents an organic group, B represents an aromatic-containing organic group having a linking oxygen attached to the aromatic ring, and m=0 or 1, with the proviso that HO—Ar 2 —C(R 8 ) 2 —Ar 2 —(B) m —OH does not represent bisphenol-A. 
 
     
     
         39 . The method of  claim 38  wherein the at least one hydroxy-containing compound of the formula (Formula I) is selected from the group consisting of diethyl tartrate, 2-hydroxybenzyl alcohol, 3-hydroxybenzyl alcohol, 2,3-dihydroxypyridine, 4,4′-(1-phenylethylidene)bisphenol, 4,4′-isopropylidenebis(2,6-dimethylphenol), 4,4′-(1,4-phenylenediisopropylidene)bisphenol, and combinations thereof. 
     
     
         40 . The method of  claim 38  wherein the compound of the formula (Formula IV) is represented by Formula IV(a): 
       
         
           
           
               
               
           
         
       
       wherein each R 9  and R 19 , independently represents hydrogen or an organic group. 
     
     
         41 . The method of  claim 40  wherein each R 9  and R 19  represents hydrogen. 
     
     
         42 . The method of  claim 38  wherein the components further comprise at least one diol different than at least one hydroxy-containing compound of the formula (Formula I). 
     
     
         43 . The method of  claim 42  wherein the at least one diol is selected from the group consisting of ethyleneglycol, diethyleneglycol, triethyleneglycol, tetra(ethyleneglycol), 1,3-propanediol, 1,4-butanediol, neopentyl glycol, 2,5-hexanediol, 1,6-hexanediol, 1,12-dodecanediol, 1,4-cyclohexanedimethanol, 4-hydroxybenzyl alcohol, 4,4′-biphenol, bis(4-hydroxyphenyl)methane, bisphenol-A, hydroquinone, 4-benzenedimethanol, 2-methoxyhydroquinone, 2,3-dimethylhydroquinone, and combinations thereof. 
     
     
         44 . The method of  claim 38  wherein the components further comprise at least one mono-hydroxy-containing compound. 
     
     
         45 . The method of  claim 44  wherein the at least one mono-hydroxy-containing compound is selected from the group consisting of methanol, ethanol, propanol, butanol, pentanol, hexanol, decanol, dodecanol, 2-methoxyethanol, 2-ethyoxyethanol, di(ethyleneglycol) monomethyl ether, di(ethyleneglycol)monoethyl ether, tri(ethyleneglycol)monomethyl ether, tri(ethyleneglycol)monoethyl ether, tetra(ethyleneglycol)monomethyl ether, tetra(ethyleneglycol)monoethyl ether, and combinations thereof. 
     
     
         46 . The method of  claim 38  wherein combining components further comprises combining a polymerization agent. 
     
     
         47 . The method of  claim 46  wherein the polymerization agent comprises a Lewis acid or a Brønsted-Lowry acid. 
     
     
         48 . The method of  claim 47  wherein the Brønsted-Lowry acid is selected from the group consisting of hydrochloric acid, p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, camphorsulfonic acid, and combinations thereof. 
     
     
         49 . The method of  claim 47  wherein the Lewis acid comprises an element selected from the group consisting of Al, Fe, B, Zn, Sb, Ti, Cu, Sn, Si, and combinations thereof. 
     
     
         50 . The method of  claim 46  wherein the polymerization agent comprises an organometallic compound or a metal salt. 
     
     
         51 . The method of  claim 50  wherein the metal salt is selected from the group consisting of metal halides, metal pseudohalides, metal sulfonates, metal carboxylates, metal carbonates, and combinations thereof. 
     
     
         52 . The method of  claim 51  wherein the metal salt comprises a metal selected from the group consisting of Zn, Cs, and combinations thereof. 
     
     
         53 . The method of  claim 46  wherein the polymerization agent comprises a plurality of sites for initiating polymerization. 
     
     
         54 . The method of  claim 38  wherein combining components further comprises combining an additional polymerizable compound selected from the group consisting of orthoesters, monofunctional ketene acetals, polyfunctional ketene acetals, imagable compounds, compounds having latent reactive sites, and combinations thereof. 
     
     
         55 . The method of  claim 54  wherein the additional polymerizable compound is a ketene acetal different than the at least one ketene acetal. 
     
     
         56 . The method of  claim 38  wherein conditions effective to polymerize comprise combining at least a portion of the components without adding a solvent. 
     
     
         57 . The method of  claim 38  wherein conditions effective to polymerize comprise combining at least a portion of the components in a dry organic solvent. 
     
     
         58 . The method of  claim 38  wherein conditions effective to polymerize comprise combining at least a portion of the components under an inert atmosphere. 
     
     
         59 - 86 . (canceled) 
     
     
         87 . A method of preparing a polymer comprising combining components comprising at least one non-cyclic polyol having no primary hydroxy groups and at least one ketene acetal under conditions effective to polymerize at least a portion of the at least one ketene acetal, wherein the at least one ketene acetal is selected from the group consisting of:
 a compound of the formula (Formula IV)   
       
         
           
           
               
               
           
         
         a compound of the formula (Formula V) 
       
       
         
           
           
               
               
           
         
       
       and combinations thereof; 
       wherein:
 each R 9  and R 17  independently represents hydrogen or an organic group; 
 each R 11 , R 13 , R 15 , and R 16  independently represents an organic group; 
 R 18  represents oxygen or an organic group and p=0 or 1; 
 each R 11  can optionally be joined with R 13  to form one or more rings; and 
 geminal R 15  and R 16  groups can optionally be joined to each other to form rings. 
 
     
     
         88 . The method of  claim 87  wherein the compound of the formula (Formula IV) is represented by Formula IV(a): 
       
         
           
           
               
               
           
         
       
       wherein each R 9  and R 19  independently represents hydrogen or an organic group. 
     
     
         89 . The method of  claim 88  wherein each R 9  and R 19  represents hydrogen. 
     
     
         90 . The method of  claim 87  wherein the at least one non-cyclic polyol is a diol having two secondary hydroxy groups. 
     
     
         91 . The method of  claim 87  wherein the at least one non-cyclic polyol is of the formula HO—CH(R 1 )—(C(R 3 ) 2 ) r —CH(R 2 )—OH; 
       wherein:
 each R 1  and R 2  independently represents an organic group; 
 each R 3  independently represents hydrogen or an organic group; and 
 r is 0 to 20. 
 
     
     
         92 . The method of  claim 91  wherein each R 1  and R 2  independently represents an organic moiety; and each R 3  independently represents hydrogen or an organic moiety. 
     
     
         93 . The method of  claim 92  wherein each R 1  and R 2  represents methyl; each R 3  represents hydrogen; and r is 0 to 2. 
     
     
         94 . The method of  claim 87  wherein the at least one non-cyclic polyol is selected from the group consisting of 2,3-butanediol, 2,4-pentanediol, 2,5-hexanediol, and combinations thereof. 
     
     
         95 - 102 . (canceled)