ABSTRACT
The concentrations of putrescine, cadaverine, indole and skatole were determined in the saliva of healthy human volunteers upon waking and at time points during the day. Putrescine was found to be the most abundant of the amines studied, followed by cadaverine then indole. Skatole could not be detected in the saliva samples at any time point. The amines were found in the highest concentrations immediately upon waking (mean concentrations (microg/ml): putrescine 33.0+/-19.0, cadaverine 17.6+/-16.7 and indole 0.4+/-0.4) with a rapid decrease following consumption of breakfast and brushing their teeth (mean concentrations (microg/ml): putrescine 7.0+/-6.4, cadaverine 3.1+/-4.7 and indole 0.04+/-0.09). Putrescine and cadaverine then increased in concentration during the day apart from a decrease post-lunch caused by increased salivary flow and mechanical cleaning due to mastication. An analytical method based on high performance liquid chromatography and fluorescence detection has been developed to quantify amines in human saliva. Sodium fluoride has been shown to be an effective inhibitor of amine formation in saliva at room temperature allowing samples to be collected and kept without requiring cold storage.
Subject(s)
Circadian Rhythm/physiology , Polyamines/metabolism , Saliva/metabolism , Adolescent , Adult , Cadaverine/metabolism , Female , Humans , Indoles/metabolism , Male , Middle Aged , Putrescine/metabolism , Skatole/metabolismSubject(s)
Anti-Infective Agents, Local/administration & dosage , Cyclodextrins/chemistry , Polymers/chemistry , Triclosan/administration & dosage , Animals , Anti-Infective Agents, Local/chemistry , Chromatography, High Pressure Liquid , Delayed-Action Preparations , Diffusion , Drug Carriers , In Vitro Techniques , Mouth Mucosa/metabolism , Swine , Triclosan/chemistryABSTRACT
The aqueous solubility of triclosan is only about 10 microg/mL. This very low solubility can hamper its biological activity in the oral cavity, which could explain the mixed clinical results obtained from triclosan toothpaste trials. Triclosan availability in a silica-based toothpaste was improved through cyclodextrin solubilization. The triclosan in vivo availability was optimized through a series of phase-solubility studies and triclosan release studies. It was found that in toothpastes, natural beta-cyclodextrin (betaCD) was just as good a solubilizer as the more water-soluble betaCD derivatives. Furthermore, the amount of cyclodextrin could be reduced by as much as 60% through the addition of a small amount of carboxymethylcellulose (CMC), without affecting triclosan release from the toothpaste. Optimally, cyclodextrins resulted in an almost 3-fold enhancement of triclosan availability compared to an identical toothpaste containing no cyclodextrin. In vivo studies in humans showed that replacing triclosan with triclosan/betaCD in the toothpaste resulted in only moderate improvement in triclosan substantivity. However, replacing triclosan with triclosan/betaCD/CMC complex resulted in significant improvement in triclosan substantivity. Furthermore, the in vivo studies showed that replacing free triclosan with triclosan/betaCD/CMC complex resulted in an almost 3-fold increase in initial triclosan concentration in saliva after brushing and about 2-fold increase in duration of activity.
