Evaluation of 2-Phosphono-butane 1,2,4 Tricarboxylate as a Crystal Growth Inhibitor in vitro and in vivo

Abstract

The inhibitory activity of 2-phosphono-butane 1,2,4 tricarboxylic acid (PBTA) in the formation of hydroxyapatite (HA) was studied in vitro and in vivo. PBTA, at 4 ppm, inhibited the spontaneous formation of HA in vitro from a supersaturated solution. PBTA, at 2 ppm, completely inhibited the crystal growth of HA; at lower concentrations, a direct relationship was found between the reduction of the initial precipitation rates and PBTA concentrations in the solution. The effects of PBTA on human dental enamel in vitro were also evaluated at pH 5.0 and 7.5. Equimolar levels of EDTA served as the controls. In comparison with EDTA, the dissolution of enamel induced by PBTA was negligible. One percent solution of PBTA was evaluated in a rat calculus assay. In comparison with a placebo solution, it significantly (p = 0.05) reduced calculus formation when applied topically. It was also tested against calculus formation in beagle dogs. A topical application once a day of a 1% solution at pH 7.0 reduced calculus formation by 84% for 16 weeks. Analysis of these data suggests that the agent effectively reduces calculus formation in vivo.