Functional biodegradable polymers

Abstract

Biodegradable polyesters are made by synthesizing copolymers derived from biodegradable hydroxyacid monomers as well as from hydroxyacid monomers containing a functional group such as an azide group, a halogen group, a thioacetate group, and the like. Preferably, the functionalized biodegradable polyester copolymers are derived from a functionalized hydroxyacid such as a homolog of lactic acid and/or glycolic acid with the copolyester thus containing functional groups on the backbone thereof. These biodegradable polyesters can be utilized wherever biodegradable polyesters are currently used, and also serve as a polymer to which various medical and drug delivery systems can be attached.

What is claimed is:  
     
         1 . A functionalized biodegradable copolyester, comprising;
 repeat units derived from one or more diols containing from 2 to about 10 carbon atoms and one or more dicarboxylic acids containing from 2 to about 15 carbon atoms, or repeat units derived from one or more hydroxyacids containing from 2 to about 20 carbon atoms, or both;   repeat units derived from one or more functionalized hydroxyacids; and   wherein said copolyester is a random, statistical copolymer and is biodegradable.   
     
     
         2 . The functionalized biodegradable copolyester of  claim 1 , wherein the amount of said functionalized repeat units is from about 10 to about 99 mole %; and wherein said hydroxyacid comprises glycolic acid, galactaric acid, hydroxypropionic acid, lactic acid, hydroxybutyric acid, hydroxyisobutyric acid, hydroxy methylbutyric acid, bis(hydroxymethyl)propionic acid, gibberellic acid, hydroxyoctadecanoic acid, di-tert-butyl hydroxybenzoic acid, benzilic acid, hydroxyl fluorenecarboxylic acid, hydroxydecanoic acid, hydroxynaphthalenecarboxylic acid, hydroxybenzenedicarboxylic acid, hydroxymethylbenzoic acid, hydroxyphenylacetic acid, mandelic acid, hydroxymethoxybenzoic acid, methoxysalicylic acid, hydroxyoctanoic acid, hydroxycinnamic acid, dihydroxycinnamic acid, dihydroxyhydrocinnamic acid, hydroxyphenylpropionic acid, dihydroxytartaric acid, hydroxymethoxycinnamic acid, salicylic acid, citrazinic acid, galacturonic acid, glucuronic acid, hydroxypropanedioic acid, hydroxyphenyl propionic acid, methoxysalicylic acid, tartaric acid, or trihydroxybenzoic acid, or any combination thereof. 
     
     
         3 . The functionalized biodegradable copolyester of  claim 2 , wherein said functionalized hydroxyacid is HHPPA, chlorohydroxybenzoic acid, chloromandelic acid, chlorosalicylic acid, dibromo hydroxybenzoic acid, dichlorohydroxy benzoic acid, dichlorosalicyclic acid, a hydroxyacid containing a halogen group other than said preceding acids, a hydroxyacid containing an azide group, or a hydroxyacid containing a thioacetate group, or any combination thereof. 
     
     
         4 . The functionalized biodegradable copolyester of  claim 3 , wherein the amount of said functionalized repeat units is from about 30 to about 80 mole %; wherein the number average molecular weight of said copolyester is from about 2,000 to 40,000 Da; and wherein said functionalized group is said halogen, said azide, or said thioacetate. 
     
     
         5 . The functionalized biodegradable copolyester of  claim 4 , including repeat units derived from said lactic acid, or said glycolic acid, or both. 
     
     
         6 . The functionalized biodegradable copolyester of  claim 5 , wherein said number average molecular weight of said copolyester is from about 6,000 to about 25,000 Da; and wherein said functional group exists on the backbone of said copolyester. 
     
     
         7 . The functionalized biodegradable copolyester of  claim 6 , wherein the amount of said functionalized monomer is from about 35 to about 50 mole %; including said repeat units derived from said lactic acid and including said repeat units derived from said glycolic acid, and wherein the amount of said lactic acid and said glycolic repeat units is from about 20 to about 80 mole % based upon the total number of said lactic acid and said glycolic acid repeat units. 
     
     
         8 . A process for synthesizing a functionalized biodegradable copolyester comprising the steps of:
 reacting one or more diols containing from 2 to about 10 carbon atoms with one or more dicarboxylic acids containing from 2 to about 15 carbon atoms, or reacting one or more hydroxyacids containing from 2 to about 20 carbon atoms, or both; with one or more functionalized hydroxyacids at low pressure and elevated temperature in the presence of a protonic acid catalyst or a Lewis acid catalyst.   
     
     
         9 . The process of  claim 8 , wherein said pressure is about 50 mm Hg or less; wherein said temperature is from about 50° C. to about 180° C; and
 wherein said hydroxyacid comprises glycolic acid, galactaric acid, hydroxypropionic acid, lactic acid, hydroxybutyric acid, hydroxyisobutyric acid, hydroxy methylbutyric acid, bis(hydroxymethyl)propionic acid, gibberellic acid, hydroxyoctadecanoic acid, di-tert-butyl hydroxybenzoic acid, benzilic acid, hydroxyl fluorenecarboxylic acid, hydroxydecanoic acid, hydroxynaphthalenecarboxylic acid, hydroxybenzenedicarboxylic acid, hydroxymethylbenzoic acid, hydroxyphenylacetic acid, mandelic acid, hydroxymethoxybenzoic acid, methoxy salicylic acid, hydroxyoctanoic acid, hydroxycinnamic acid, dihydroxycinnamic acid, dihydroxyhydrocinnamic acid, hydroxyphenylpropionic acid, dihydroxytartaric acid, hydroxymethoxycinnamic acid, salicylic acid, citrazinic acid, galacturonic acid, glucuronic acid, hydroxypropanedioic acid, hydroxyphenyl propionic acid, methoxy salicylic acid, tartaric acid or trihydroxybenzoic acid or any combination thereof. 
 
     
     
         10 . The process of  claim 9 , wherein the amount of said functionalized hydroxyacid is from about 30 to about 80 mole % based upon the total number of moles of said one or more functionalized hydroxyacids and said one or more non-functionalized hydroxyacids; and wherein the number average molecular weight of said functionalized biodegradable copolyester is from about 2,000 Da to about 40,000 Da. 
     
     
         11 . The process of  claim 10 , wherein said pressure is about 10 mm Hg or less; and wherein said functionalized hydroxyacid is HHPPA, chlorohydroxybenzoic acid, chloromandelic acid, chlorosalicylic acid, dibromo hydroxybenzoic acid, dichlorohydroxy benzoic acid, dichlorosalicyclic acid, a hydroxyacid containing a halogen group other than said preceding acids, a hydroxyacid containing an azide group, or a hydroxyacid containing a thioacetate group, or any combination thereof. 
     
     
         12 . The process of  claim 11 , wherein said catalyst comprises p-dimethylaminopyridinium toluenesulphonate (DPTS), p-toluidine hydrochloride, dimethyl-p-phenylenediamine dihydrochloride, p-toluenesulphonic acid, or SnCl 2 , or any combination thereof. 
     
     
         13 . The process of  claim 12 , wherein the amount of said one or more functionalized hydroxyacids are from about 35 to about 50 mole %; including said repeat units derived from said lactic acid or including said repeat units derived from said glycolic acid, or both, and wherein the amount of said lactic acid repeat units is from about 20 to about 80 mole % based upon the total number of said lactic acid and said glycolic acid repeat units; and wherein catalyst is p-toluene sulphonic acid. 
     
     
         14 . The process of  claim 8 , including further reacting said biodegradable functionalized copolyester with a linking agent and a protonic catalyst or a Lewis acid catalyst at ambient temperature. 
     
     
         15 . The process of  claim 11 , including further reacting said biodegradable functionalized copolyester with a linking agent and a protonic catalyst or a Lewis acid catalyst at ambient temperature.