Synthesis

1. polycondensation of glycolic acid;
2. ring-opening polymerization of glycolide;
3. solid-state polycondensation of halogenoacetates;
4. acid catalyzed reaction of carbon monoxide and formaldehyde

Polycondensation of glycolic acid is the simplest process available to prepare PGA, but it is not the most efficient because it yields a low molecular weight product. Briefly, the procedure is as follows: glycolic acid is heated at atmospheric pressure and a temperature of about 175-185° C is maintained until water ceases to distill. Subsequently, pressure is reduced to 150 mm Hg, still keeping the temperature unaltered for about two hours and the low MW polyglycolide is obtained.Lowe, C. E.: "Preparation of high molecular weight polyhydroxyacetic ester", U.S. Pat 2 668 162, 1954

The most common synthesis used to produce a high molecular weight form of the polymer is ring-opening polymerization of "glycolide", the cyclic diester of glycolic acid. Glycolide can be prepared by heating under reduced pressure low MW PGA, collecting the diester by means of distillation. Ring-opening polymerization of glycolide can be catalyzed using different catalysts, including antimony compounds, such as antimony trioxide or antimony trihalides, zinc compounds (zinc lactate) and tin compunds like, stannous octoate (Tin(II) 2-Ethylhexanoate) or tin alkoxides. Stannous octoate is the most common used initiator, since it is approved by the FDA as a food stabilizer. Usage of other catalysts has been undisclosed as well, among these are aluminum isopropoxide, calcium acetylacetonate and several lanthanide alkoxides (e.g. yttrium isopropoxide). The procedure followed for ring-opening polymerization is briefly outlined: a catalytic amount of initiator is added to glycolide under a nitrogen atmosphere at a temperature of 195° C. The reaction is allowed to proceed for about two hours, then temperature is raised to 230° C for about half an hour. After solidification the resulting high MW polymer is collected.

Another procedure consists in the thermally induced solid-state polycondensation of halogenoacetates with general formula X-—CH₂COO^-M⁺ (where M is a monovalent metal like sodium and X is a halogen like chlorine), resulting in the production of polyglycolide and small crystals of a salt. Polycondensation is carried out by heating an halogenoacetate, like sodium chloroacetate, at a temperature between 160-180° C, continuously passing nitrogen through the reaction vessel. During the reaction polyglycolide is formed along with sodium chloride which precipitates within the polymeric matrix; the salt can be conveniently removed by washing the product of the reaction with water.

PGA can also be obtained by reacting carbon monoxide, formaldehyde or one of its related compunds like paraformaldehyde or trioxane, in presence of an acidic catalyst. In a carbon monoxide atmosphere an autoclave is loaded with the catalyst (chlorosulfonic acid), dichloromethane and trioxane, then it is charged with carbon monoxide until aspecific pressure is reached; the reaction is stirred and allowed to proceed at a temperature of about 180° C for two hours. Upon completion the unreacted carbon monoxide is discharged and a mixture of low and high MW polyglycolide is collected.Masuda et al.: "Biodegradable plastic composition", U.S. Pat 5 227 415, 1993

Degradation

When exposed to physiological conditions, polyglycolide is degraded by random hydrolysis and apparently it is also broken down by certain enzymes, especially those with esterase activity. The degradation product, glycolic acid, is non toxic and it can enter the tricarboxylic acid cycle after which it is excreted as water and carbon dioxide. A part of the glycolic acid is also excreted by urine.

Studies undergone using polyglycolide-made sutures have shown that the material loses half of its strenght after two weeks and 100% after four weeks. The polymer is completely resorbed by the organism in a time frame of four to six months.

Uses