Synopsis
I n order to study structure-tissue reactivity relationships arid ultimately develop a less necrotizing adhesive, this laboratory undertook a study of the synthesis and degradation of the homologous series of a-cyanoacrylate monomers and polymers. A method for synthesizing high purity cyanoacrylates and some of their chemical and physical properties are presented. In vitro kinetics studies under heterogeneous and homogeneous conditions indicate that cyanoacrylate polymers degrade by hydrolytic scission of the polymer chain. The products resulting from such a scission are formaldehyde (positively identified by derivative formation) and ultimately an alkyl cyanoacetate. As the homologous series is ascended, the rate of degradation under neutral conditions decreases. In homogeneous solution, under alkaline conditions, the rate of degradation is considerably higher than under neutral conditions and the rates obtained with the methyl to the butyl derivative are of the same order. A proposed mechanism of degradation is presented. Medical evaluation has indicated that as the homologous series is ascended, the greater the tissue tolerance to the monomers and polymers. The relevance of the results of the in vitro studies to this medical finding is presented.
The capability of rapidly polymerizing monomeric a-cyanoacrylates to adhere firmly to moist surfaces has evoked considerable medical interest in their potentialities as hemostatic agents and tissue adhesives for closure of wounds in place of, or as adjuncts to, the conventional surgical sutures.l Evaluation of methyl a-cyanoacrylate in such applications revealed that tissue inflammation and cell necrosis occurred in experimental animals.2n3 Research in this laboratory further showed that the P-14C-tagged methyl a-cyanoacrylate polymer was degraded gradually in vivo4 and was excreted in the urine and feces with none of the radioactive entities being retained in vital tissues or organs. Concomitantly, it was discovered4 that the polymer of methyl a-cyanoacrylate underwent degradation in contact with distilled water in vitro, giving rise to formaldehyde, analogous to the degradation of poly(viny1idene cyanide) , reported by Gilbert and CO-worker^.^
In order to elucidate structuretissue reactivity relationships and ultimately develop a less necrotizing adhesive, this laboratory undertook the