Anti-gingivitis Active Ingredients

To date, two antimicrobial, gingivitis-fighting agents have been successfully added to toothpastes to target plaque and gingivitis: triclosan and stannous fluoride. Triclosan, a broad-spectrum antimicrobial, acts by disrupting the cytoplasmic membrane.⁷³ Triclosan was the active ingredient used in Colgate Total^® for many years until the product was reformulated and removed. Triclosan is no longer incorporated in toothpaste formulations following potential safety concerns.⁷⁴

Stannous fluoride (SnF₂) is distinctive among the three fluorides shown in Figure 3 in that it has multiple functions beyond caries prevention. Notably, stannous fluoride also is a clinically proven effective antimicrobial: five systematic reviews/meta-analyses have found significant superior gingivitis and gingival bleeding reductions compared to various toothpaste controls in long term clinical trials.^75-80 The bacteriostatic and bactericidal mechanisms of SnF₂ do not fade quickly after brushing; activity can be present up to 12 hours later.^81,82 Subgingival plaque sampling using P&G formulations in a clinical trial detected SnF₂ anti-inflammatory activity following brushing up to 4 mm below the gumline.⁸³ It has long been known to improve gingival health via decreasing the growth and adhesion of bacteria, as well as reducing acid production and toxic metabolic products that are factors in gingival inflammation and bleeding.^81,82,84 More recently, research has demonstrated that SnF₂ in a stabilized bioavailable dentifrice formulation additionally interacts directly with bacterial endotoxins to reduce pathogenicity, i.e., it modulates the process of gingival inflammation by binding pathogens to blunt the immune response.^84-91

Formulation acumen is critical when it comes to stannous fluoride toothpastes, because SnF₂will not have optimum bioavailability if the dentifrice technology does not account for various ingredient combinations which can impede its effectiveness or hinder stability, substantivity, or esthetics.^92-95 At least three dentifrice manufacturers now offer stannous fluoride plaque- and gingivitis-fighting toothpastes, each with 0.454% stannous fluoride but differing SnF₂ systems. One dental professional shared the opinion in an online dentifrice review, “Stannous fluoride is stannous fluoride is stannous fluoride.”⁹⁶ However, the magnitude of anti-gingivitis benefits for the marketed SnF₂ dentifrice examples listed below can vary based on the specific amalgamation of the components in the formula, and the interventions taken to ameliorate factors such as oxidation and SnF₂ deactivation.^95,97 These affect the stannous fluorides’ ability to be bioavailable to penetrate the biofilm and neutralize toxins to exert the desired therapeutic effect.

The Crest^® brand has a long history of utilizing stannous fluoride (the original 1960s Crest featured Fluoristan^®) for both caries prevention and gum health benefits. The formulation has been optimized over time to increase stability and efficacy with maximally compatible abrasive systems to provide for maximum bioavailability for anti-plaque and gingival health benefits.^94,95 Crest ProHealth and Crest Gum Detoxify contain 0.454% bioavailable stannous fluoride with citrate. The manufacturer cites over 100 SnF₂ clinical trials demonstrating significantly greater anti-plaque and/or anti-gingivitis benefits for the gluconate-chelated SnF₂ bioavailable family of toothpastes compared to other dentifrices.⁹⁸A published meta-review of 18 randomized controlled clinical trials of almost 3000 subjects comparing SnF₂ bioavailable stannous fluoride with the same formulation to toothpaste controls concluded that SnF₂ reduced the average number of bleeding sites by 51% compared to non-antimicrobial dentifrices.⁷⁸ In addition, participants with gingivitis had 3.7 times better odds of moving to “generally healthy” status (<10% bleeding sites) when using the SnF₂ dentifrice compared to those using a negative control. And in a 3-month randomized, controlled clinical trial, 3/4 of subjects brushing with a ProHealth SnF₂ formulation transitioned from generalized/localized gingivitis to generally healthy, compared to no subjects in another marketed 0.454% SnF₂ control group.⁹⁷ The former provided 78% fewer bleeding sites relative to the comparator 0.454% SnF₂ dentifrice at Month 3.

Another Crest formulation change included the introduction of the amino acid glycine. This unique amino acid further stabilizes the stannous formulation, delivering 180% more tin delivery into the biofilm than a stannous positive control without glycine, allowing for deeper penetration into the biofilm and allowing access to neutralize the most virulent toxins at the depth of the biofilm.⁹⁹

The majority of Colgate Total products have been reformulated with 0.454% stannous fluoride. The new SnF₂ multi-benefit formulation – in development for 10 years – is a patented inactive zinc phosphate system that enables SnF₂ to remain stable and active in delivering its intended benefits.¹⁰⁰ Two published six-month clinical studies demonstrated that Colgate Total with stannous fluoride was superior to a regular fluoride dentifrice¹⁰¹ (Figure 9), and comparable to another marketed 0.454% SnF₂ dentifrice¹⁰² for the reduction of plaque and gingivitis.

Figure 9.

Figure 9.

Source: Colgate Professional. Colgate Total

Plaque reduction of a 0.454% SnF₂ dentifrice stabilized with zinc phosphate versus a negative control.

GlaxoSmithKline’s (GSK Consumer Healthcare) Parodontax^TM was available through the 1990s as an herbal/sodium bicarbonate formulation, but was reformulated and relaunched with 0.454% stannous fluoride as the active ingredient, stabilized in a non-aqueous base, and incorporated sodium tripolyphosphate.¹⁰³ In a 6-month published clinical trial, using Parodontax resulted in a 40% reduction in gingival bleeding versus baseline compared to an MFP negative control toothpaste.¹⁰⁴ GSK also manufactures Sensodyne Complete Protection^® , which contains the same 0.454% SnF₂ technology as Parodontax. This dentifrice was found in a 6-month clinical trial to provide 35.5% significantly better gingival bleeding site reduction compared to an MFP negative control toothpaste.¹⁰⁵