Triclosan (2,4,4',-trichloro-2'-hydroxydiphenylether) is a well-known and widely used nonionic antibacterial agent which has recently been introduced in toothpastes and mouthrinses. The efficacy of triclosan-containing toothpaste and mouthrinse to reduce both plaque and gingivitis in long-term clinical trials has been well documented. Until recently, it was generally assumed that triclosan's effect on gingival inflammation was due to its antimicrobial and anti-plaque effect. It has now become apparent that triclosan may have a direct anti-inflammatory effect on the gingival tissues. Several in vitro studies were conducted to evaluate the effect of triclosan on 4 primary enzymes of the pathways of arachidonic acid metabolism, cyclo-oxygenase 1, cyclo-oxygenase 2, 5-lipoxygenase and 15-lipoxygenase. These pathways lead to the production of known mediators of inflammation such as the prostaglandins, leukotrienes and lipoxins. Triclosan inhibited both cyclooxygenase 1 and cyclo-oxygenase 2 with IC-50 values of 43 microM and 227 microM, respectively. Triclosan also inhibited 5-lipoxygenase with an IC-50 of 43 microM. The 15-lipoxygenase was similarly inhibited by triclosan with an IC-50 of 61 microM. Hence, triclosan has the ability to inhibit both the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism with similar efficacy. In cell culture experiments, it was found that triclosan inhibited IL-1 beta induced prostaglandin E2 production by human gingival fibroblasts in a concentration dependent manner, and at relatively low concentrations. These data, taken together, indicate that triclosan can inhibit formation of several important mediators of gingival inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

This presentation provides an overview of the technologies available for the chemical control of plaque. It is generally accepted that the formation of dental plaque at the interfaces of tooth/gingiva is one of the major causes of gingival inflammation and dental caries. Several therapeutic approaches have been used to control dental plaque and supragingival infections. These include fluoride preparations such as stannous fluoride, oxygenating agents, anti-attachment agents, and cationic and non-cationic antibacterial agents. Among the fluoride preparations, stable stannous fluoride pastes and gels have been shown to reduce supragingival plaque, gingivitis, hypersensitivity and caries. The effect of the oxygenating agents on the supragingival plaque has been equivocal, but recent data indicate that a stable agent which provides sustained active oxygen release is effective in controlling plaque. A polymer, PVPA, which reduced attachment of bacteria to teeth was shown to significantly reduce plaque formation in humans. A new generation of antibacterials includes non-ionics such as triclosan, which in combination with a special polymer delivery system, has been shown to reduce plaque, gingivitis, supragingival calculus and dental caries in long-term studies conducted around the world. Unlike the first generation of agents, the triclosan/copolymer/sodium fluoride system is effective in long-term clinicals and does not cause staining of teeth, increase in calculus, or disturbance in the oral microbial ecology.

Salifluor (5-n-octanoyl-3'-trifluoromethyl-salicylanilide), a broad spectrum antimicrobial agent, was investigated for its ability to inhibit dental plaque formation. A combination of salifluor with PVM/MA copolymer and NaF was optimized for its antiplaque effect in mouthrinse and dentifrice formulations based on a series of both laboratory and clinical studies. It was found that salifluor, a highly hydrophobic compound, could not be adequately solubilized with the conventional amount of sodium lauryl sulfate (SLS), the most commonly used anionic surfactant in oral hygiene products. However, it was possible to prepare stable mouthrinse formulations using a mixed surfactant system containing both anionic and nonionic surfactants. The most suitable mixture was found to be a combination of SLS, Pluronic and Tauranol in a proportion of 1:1:1. This combination provided adequate stability and high antimicrobial activity as determined by in vitro microbiological tests. Addition of a PVM/MA copolymer to the formulation improved the adsorption and retention of salifluor on stimulated tooth surfaces in vitro (saliva coated hydroxyapatite disks) by almost two-fold and also increased the antiplaque efficacy in both laboratory and human clinical studies. It was also found that a non fluoride dentifrice containing a combination of salifluor and PVM/MA copolymer with a dicalcium phosphate dihydrate abrasive, was highly effective in reducing smooth surface and fissure caries in rats. The results of the present studies demonstrated that salifluor is an effective antiplaque agent in mouthrinse and dentifrice when carefully formulated to maximize its delivery and bioavailability on oral surfaces. They also illustrated the difficulties encountered in exploiting the antimicrobial efficacy of highly hydrophobic, nonionic antimicrobial agents such as salifluor in commonly used oral hygiene vehicles.

We developed an experimental in vitro model of dental plaque to assess the potential efficacy of antiplaque agents. The model used a chemostat, which provided a continuous source of 5 species of oral bacteria grown in an artificial "saliva-like" medium. This mixture was pumped through six flow cells, each containing two types of surfaces on which plaque formed and was subsequently measured. Formation of bacterial plaque on hydroxyapatite surfaces was assessed by measurement of the DNA and protein content of the plaque film. The amount of bacterial plaque formed on germanium surfaces was measured by attenuated total reflectance (ATR/FT-IR) spectroscopy. Plaque viability was also assessed by a fluorescent staining technique. The quantity of plaque formed on both types of surfaces gradually increased with the duration of flow (from 24 to 72 h) through the cells during a 72-hour experimental period. The flow cells were then pulsed with experimental treatment solutions for 30 s, twice daily. Parallel to results of human clinical studies, the model was capable of discriminating among water, a placebo mouthrinse, and an active antimicrobial mouthrinse formulation containing 0.03% triclosan. It therefore offers a valuable alternative to animal model testing and allows for more rapid evaluations under well-controlled experimental conditions.

Studies were conducted to determine fluoride availability in saliva after dentifrice use and to relate this parameter to cariostatic efficacy in rat caries experiments. Three dentifrices--two commercial formulations (Colgate Winterfresh Gel and Crest Dentifrice with Na-Sr-polyacrylate) and an Experimental dentifrice--were compared with respect to salivary fluoride availability. All of the dentifrices tested contained 1100 ppm F as sodium fluoride. It was observed that the Experimental dentifrice and Crest dentifrice with Sr-polyacrylate exhibited low salivary fluoride availability relative to the Colgate Winterfresh Gel. Salivary fluoride availability was assessed by means of two parameters: (a) the fluoride concentration in the dentifrice saliva slurry expectorated after brushing, and (b) the area under the curve of salivary F concentration vs. time for up to two hours after dentifrice use. In two rat caries experiments, it was observed that both the Experimental dentifrice and the Sr-polyacrylate dentifrice provided less cariostatic efficacy than the clinically validated Positive Control (Colgate Winterfesh Gel). Analysis of these data provides further evidence in support of the concept that fluoride availability in saliva following dentifrice use is an important parameter related to anticaries efficacy.