The antimicrobial combination effects of o-Cymen-5-ol and Zinc

Antimicrobial ingredients have been suggested to be added to oral health products to deliver plaque control and gingivitis benefits. Objectives: To evaluate antimicrobial effects of o-cymen-5-ol and zinc, alone and in combination, in simple solutions and whole toothpaste formulations. Methods: Solutions of o-cymen-5-ol and zinc gluconate up to 6.7mM and 44mM were evaluated in minimum inhibitory concentration (MIC) or minimum bactericidal concentration (MBC) assays against five microorganisms: Streptococcus mutans, Actinomyces viscosus, Porphyromonas gingivalis, Fusobacterium nucleatum and Candida albicans; synergy was investigated in checkerboard MIC/MBC assays; inhibitory effects were assessed on S.mutans glycolysis and protease activity of P. gingivalis. The effects of o-cymen-5-ol and zinc chloride formulated into toothpastes at 0.1%w/w (6.7mM) and 0.6%w/w (44mM), respectively and slurried at 16.7% and 25%w/w were assessed by killtime (modified EN1276) assays against S.mutans. Results: The MIC for o-cymen-5-ol was between 1.7mM and 3.4mM and MBC between 3.4mM and 6.7mM; for zinc gluconate the MIC was between 2.8mM and 11mM and MBC between 11mM and >44mM. Combinations of the two agents in solution showed significant synergistic effects (FICI≤0.50) in MIC/MBC tests against oral anaerobic species, with effective MIC values as low as 0.42mM/0.69mM for the combination of o-cymen-5-ol/zinc gluconate, respectively. Both glycolysis and protease activity were inhibited to a greater extent by zinc than by o-cymen-5-ol; additive effects were seen for the combination of agents in glycolysis inhibition. In whole toothpastes the combination showed significantly greater effects (log10 kill = 7.35±0.40) than placebo paste (log10 kill = 4.02±0.40). Conclusions: Combinations of zinc and o-cymen-5-ol produced antimicrobial effects against a range of oral microorganisms and important disease-related processes. Significant synergistic antimicrobial effects were seen against oral anaerobes. O-cymen-5-ol and zinc show a range of properties desirable for incorporation in toothpastes.