SYNTHESIS |
Poly[bis(p-carboxyphenoxy)methane]hereinafter "PCPM" was chosen as the prototype to demonstrate the usefulness of polyanhydride polymers as matrices for the controlled release of biologically active substances. The PCPM homopolymers were prepared by the modification of the Conix methodology previously described [Macromolecular Synthesis 2:95-98 (1966)]. The modification is a recrystallization of the prepolymer to yield a more pure product, prior to formation of the homopolymer. Accordingly, 0.3 moles of bis(p-carboxyphenoxy)methane, the dicarboxylic acid precursors of (p-carboxyphenoxy)methane were combined with 600 ml of acetic anhydride and converted to the prepolymer anhydride form by total reflux for 30 minutes. Caution was taken to avoid excessive reflux reaction which would yield a highly insoluble prepolymer more difficult to purify. The prepolymers isolated were further purified by recrystallization in a 50:50 (v/v) mixed solvent of acetic anhydride and dimethylformamide. The recrystallization period was sometimes extended to several weeks in order to obtain a reasonable yield of 30% or more. The prepolymers then underwent melt polycondensation in vacuo under nitrogen sweep. The resulting PCPM polyanhydride was a yellow, translucent, amorphous solid having a glass transition temperature of 92.degree. C. Testing by infrared spectroscopy demonstrated that this PCPM polymer had carbonyl stretching frequencies of 1770 and 1720 centimeters respectively. No attempt to evaluate the degree of polymerization or the molecular weight of the final PCPM polymer was made; such information was deemed to be unimportant with respect to the characteristics of PCPM which made it useful as a matrix for delivery of biologically active substances.
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