Polyanhydrides dicarboxylic acid monomers

Polyanhydrides are useful bioabsorbable materials for controlled drug delivery. They hydrolyze to dicarboxylic acid monomers when placed in aqueous medium. Since their introduction to the field of controlled drug delivery, about 15 years ago, extensive research has been conducted to study their chemistry as well as their toxicity and medical applications. Several review articles have been published on polyanhydrides for controlled drug delivei y applications (Domb et al, 1992 Leong et al., 1989 Laurencin 1995). 

Polyanhydrides have been synthesized by various techniques such as melt polycondensation, ring-opening polymerization, interfacial polycondensation, dehydrochlorination, and dehydrative coupling (13,14). The most widely used technique for polyanhydride synthesis is melt polycondensation, which occurs in two steps. In the first step, dicarboxylic acid monomers react with excess acetic anhydride to form acetyl-terminated anhydride prepolymers (1) with a degree of polymerization (DP) ranging from 1 to 20 (eq. 1). 

Method of synthesis polyanhydrides can be prepared by melt condensation polymerization in which dicarboxylic acid monomer reacts with excess of acetic anhydride ... 

Polyanhydrides are among the most hydrolytically unstable polymers. These polymers were prepared first in 1909, subsequently investigated as potential textile fibers but found unstable melt-polycondensation. Here, starting from a dicarboxylic acid monomer, a prepolymer consisting of a mixed anhydride of the diacid with acetic acid is formed (Scheme 3). The polymer is obtained by subsequently heating the prepolymer under vacuum to eliminate the acetic anhydride by-product. Several aliphatic dicarboxylic acid compounds (sebacic acid (SA), fumaric acid (FA), etc.) and aromatic... 

Various combinations of dicarboxylic acid derivatives and glycols enzymatically afforded polyesters under mild reaction conditions. Dicarboxylic acids as well as derivatives, activated and non-activated esters, cyclic acid anhydride, and polyanhydrides, were found to be useful as monomer for the enzymatic synthesis of polyesters. 

The development of unsaturated polyanhydrides responded to the necessity of improving the mechanical properties of the polymers in applications such as the temporary replacement of bone. " Unsaturated polyanhydrides, prepared by melt or solution polymerization, include homopolymers of fumaric acid (FA), acetylene-dicarboxylic acid (ACDA), and 4,4 -stilbenzenedi-carboxylic acid (STDA). The chemical structures of poly(FA) and poly(ACDA) are shown in Table 1. These polymers are highly crystalline and insoluble in common organic solvents. The double bonds of these monomers make them suitable for further crosslinking to improve mechanical properties of polyanhydrides. When copolymerized with aliphatic diacids, less crystalline polymers with enhanced solubility in chlorinated solvents result. 

The Schotten-Bauman condensation produces polyanhydrides with moderate molecular weights by a dehydrochlorination reaction between a diacid chloride and a dicarboxylic acid. The polymerization takes place by reacting the monomers for 1 hr at room temperature, and it can be conducted via solution or interfacial methods. Solvents that are used in solution polymerization include dichloromethane, chloroform, benzene, and ethyl ether. The degree of polymerization obtained with this method is approximately 20-30. Lower molecular weight products are obtained for less reactive monomers such as isophthaloyl chloride. 

The solution polymerization is carried out by Schotten-Baumann technique. In this method, the solution of diacid chloride is added dropwise into an ice-cooled solution of a dicarboxylic acid. The reaction is facilitated by using an acid acceptor such as triethylamine. Polymerization takes place instantly on contact of the monomers and is essentially complete within 1 h. The solvents employed can be a single solvent or a mixture of solvents like dichlorometh-ane, chloroform, benzene, and ethyl ether. It was found that the order of addition is very important in obtaining relatively high-molecular-weight polyanhydrides. Addition of... 

Lipase-Catalyzed Polymerization of Dicarboxylic Acids or Their Derivatives. Enzymatic synthesis has been achieved via various combinations of dicarboxylic acid derivatives and glycols. As to the diacid monomer, dicarboxylic acids, activated and nonactivated esters, cyclic acid anhydrides, and polyanhydrides were enzymatically reacted with glycols under mild reaction conditions. 

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