Chemical plaque control

Introduction to chemical plaque control

The role of dental plaque in the initiation of periodontal inflammatory diseases has been well established ¹. Elimination of plaque and preventing its formation is the cornerstone of periodontal therapy. The chemical plaque control as an adjunct to mechanical plaque control has been used effectively to eliminate dental plaque. In an experimental study, it has been shown that a complete inhibition of plaque and prevention of gingivitis could be achieved by daily application of 0.2% (CHX) ². Many other studies have supported the significant plaque reduction with the use of chemical plaque control measures ^3-6. However, it must be remembered that the chemical plaque control is an adjunct to mechanical plaque control and cannot eliminate plaque when used as a monotherapy. Further, presently there is insufficient data, authenticating their long term usage.

     In “Mechanical plaque control”, we discussed various methods of mechanical plaque control. In this chapter, we shall discuss in detail various chemicals (organic and inorganic) which are used to control plaque formation by inhibiting the accumulation, growth, and survival of microbiota involved in plaque formation.

History of chemical plaque control

Probably, the first chemicals used for plaque removal were dentifrices which have been used in conjunction with mechanical aids for centuries. Egyptians used tooth powders or pastes to clean their teeth, as did the ancient Greeks and Romans. Egyptians used to chew sodium carbonate to freshen their breath. They also used to rinse their mouth with honey and water to which goose fat, frankincense, cumin, and ocher had been added. The Romans used to rinse their mouth with Portuguese urine. It was believed that ammonia in urine aided in the disinfection of mouth and could whiten teeth. This practice was so popular that Nero had to place a tax on it. The practice remained popular until the 18th century. The Chinese medicine has been credited with the first reference (around 2700 BC) to use child urine as a mouth rinse to treat gum diseases ⁷.

     During the 12th century, Saint Hildegard von Bingen, a German philosopher advised mouth rinses with pure, cold water to prevent plaque and tartar formation. In the 16th century during the medieval period, people used mint and vinegar rinsing solutions to clean their mouth and get rid of bad breath. The chemical plaque control agents which are …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Classification of chemical plaque control agents

The European Federation of Periodontology in European workshop on Periodontology in 1996 8, used four terminologies to describe various agents used for chemical plaque control,

Antimicrobial agents: According to the consensus report, these are those chemicals that have a bacteriostatic or bactericidal effect in vitro that alone cannot be extrapolated to a proven efficacy against plaque in vivo.

Plaque reducing/inhibitory agents: These are the chemicals that have only been shown to reduce the quantity and/or affect the quality of plaque, which may or may not be sufficient to influence gingivitis and/or caries.

Anti-plaque agents: These chemical agents have an effect on plaque sufficient to benefit gingivitis and/or caries.

Anti-gingivitis agents: These are the chemicals which reduce gingival inflammation without necessarily influencing bacterial plaque (includes anti-inflammatory agents).

     Another classification ^{7, 9} describes 3 generations of chemical plaque control agents. In this classification, agents in the first and second generation have been classified according to their substantivity ¹⁰.

1st generation: These are antibacterial agents with limited substantivity in vivo. They are capable of reducing plaque scores by 20-50%. The examples include antibiotics, phenols, quaternary ammonium compounds, metallic ions, sanguinarine etc.
2nd generation: These are antibacterial agents with high substantivity. They are 70-90% more effectively retained by oral tissues than first generation agents and are slowly released. An example includes Bisbiguanides.
3rd generation: These agents are relatively new preparation which inhibits plaque growth and gingivitis by interfering with the plaque matrix formation and also by reducing bacterial adhesion and adherence. An example includes Delmopinol.

Classification of chemical plaque control agents.
First generation agents	Phenols and essential oils	Thymol Hexylresorcinol Eucalyptol Triclosan
	Metal salts	Tin Zinc Copper Stannous fluoride
	Natural products	Sanguinarine Propolis
	Fluorides	Sodium fluoride Sodium monofluoro-phosphate Stannous fluoride Amine fluoride
	Antibiotics and Antimicrobial agents	Penicillin Vancomycin Kanamycin Niddamycin Spiramycin
	Quaternary ammonium compounds	Cetylpyridinium chloride Benzalconium chloride
	Oxygenating agents	Hydrogen peroxide Sodium peroxyborate Sodium peroxycarbonate
	Enzymes	Protease Lipase Nuclease Dextranase Mutanase
	Surfactants/Detergents	Sodium lauryl sulfate
Second generation agents	Bisbiguanides	Chlorhexidine Alexidine Octenidine
Third generation agents	Amine alcohols	Octapinol Delmopinol

     The chemical agents used for plaque control can act at various stages of plaque formation. The agents which interfere with the initial bacterial adhesion to the tooth surface can be considered as anti-adhesive agents. These act on the dental pellicle and prevent initial adhesion of bacteria, thus may be considered as the most effective agents for the prevention of plaque formation. Unfortunately, we do not have any effective agent in this category which can be used safely for long term without unwanted adverse effects. Some recently introduced agents such as amine alcohol and delmopinol have shown properties of inhibiting plaque matrix formation ^{11, 12}.

     The next step in plaque formation is plaque maturation which is characterized by the accumulation of Gram-positive and Gram-negative bacteria. These bacteria form a well organized structure, known as plaque biofilm. At this stage agents who inhibit the plaque maturation are the anti-microbial agents. The anti-microbial agents can act on plaque by two mechanisms: by inhibition of bacterial proliferation and by their bactericidal action. These agents inhibiting plaque bacteria, may also act on the dental pellicle as anti-adhesive agents and prevent the bacterial adhesion, thereby exerting a bacteriostatic action. These agents may also act after the colonization of bacteria on dental pellicle by inhibiting bacterial proliferation. The bactericidal agents reduce the …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

     After the formation and maturation of plaque, chemical agents may be used as plaque removal agents. In other words, we can say that these agents may be used to remove plaque in a similar way as in the mechanical plaque control. Term “chemical toothbrush” has been used to describe these agents. In oral environment, the most closely suited plaque removal agents are enzymes such as proteases or bacterial matrices (dextranase and mutanase) ¹⁴. However, the practical applicability of these enzymes in oral environment has not been well established due lack of substantivity and local side effects.

     Another approach to control the pathogenic plaque formation in the oral cavity is the probiotic approach. The word probiotic is derived from a Greek word meaning “for life”. Probiotic approach needs a detailed discussion but briefly, Lactobacilli have been shown to interact with various members of oral flora, thereby inhibiting the growth of periodontopathogenic microorganism ¹⁵. A study demonstrated significantly reduced gingival index and bacterial plaque amount in patients treated with Lactobacillus reuteri than in a placebo group. The authors concluded that this probiotic was effective in reducing gingivitis and bacterial plaque deposition in patients with moderate-to-severe gingivitis ¹⁶. Probiotics have also been shown to reduce the risk for a high Streptococcus mutans level occurrence, thereby reducing caries risk ^17-19.

     Another approach suggested by Lindhe 20 is the use of anti-pathogenic agents. These agents may reduce the pathogenicity of periodontal pathogens without necessarily destroying them. However, this approach is still hypothetical and requires more research.

Formulations containing chemical plaque control agents

Presently, there are various formulations carrying chemical plaque control agents, including dentifrices (toothpastes and tooth-powders), mouth rinses, sprays, oral irrigators, chewing gums and varnishes.

Dentifrices

Dentifrices are an integral part of daily oral health maintenance. They not only help in cleaning and polishing the teeth, but also the fresh feeling that comes with the use of a dentifrice while tooth brushing is liked by most people. These are available in paste, powder, gel or liquid form. Dentifrice is the French word for toothpaste.

History of dentifrices:

The history of dentifrices may be tracked back to the time of the Egyptians, Greeks, and Romans. Egyptians are known to make a tooth powder which consisted of ashes of ox hooves, myrrh, powdered eggshells, and pumice. Greeks improved it by adding abrasives such as crushed bones and oyster shells. Romans added powdered charcoal, powdered bark and flavoring agents in it.

     Although the prescriptions of toothpastes have been found in the Ebers Papyrus, an Egyptian medical reference book, but Hippocrates (460-377 BC) was the first to recommend the use of dentifrices. This dentifrice was made up of ashes from hares and mice, as it was believed that animals which had strong teeth may pass this attribute to humans in the form of ash. The Romans used dentifrice which was made up of the powder obtained from grinding horns and animal skulls mixed with goat’s fat. The Chinese used a mixture of salt, musk, and urine, which they believed cleaned the teeth as well as improved gingival health.

     In 1873, toothpaste was mass-produced for the first time. The major initiating factor for the development of new age dentifrices was the ‘chemo-parasitic theory of tooth decay’ proposed by WD Miller in 1890. It created a boom in the toothpaste industry and since then toothpastes with a variety of compositions and properties have been introduced in the market. The first collapsible tube containing toothpaste was made by Dr. Washington Sheffield in 1892. It was named ‘Dr. Sheffield’s Creme Dentifrice’. Soon after …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….

Toothpastes:

• Toothpastes are the most commonly used agents for the maintenance of oral health. Ideal toothpaste must have the following properties ^{21, 22},
  It should cause a slight abrasion,
• It should produce froth,
• It should have acceptable taste,
• It should have a bleaching effect, and
• It should prevent plaque, calculus and caries development.

Composition of a toothpaste:

Toothpaste is a colloidal suspension of a mixture of ingredients that must be carefully balanced in order to provide an efficacious, safe, and consumer-friendly product. The primary ingredients of toothpaste are,

• Abrasives.
• Thickening / Binding agents.
• Humectants.
• Solvents.
• Surfactants.
• Sweeteners.
• Flavoring agents.
• Coloring agents.
• Preservatives.
• Therapeutic agents.

Composition of toothpastes
Toothpaste components	Percentage by weight
Abrasive Water Humectants Detergent Thickening agent Flavor Sweetener Therapeutic agent Color or preservative	20 - 50 % 20 - 40 % 20 - 35 % 1 - 3 % 1 - 2 % 0 - 2 % 0 - 2 % 0 - 2 % 0.05 – 0.5 %

Abrasive:

The primary function of abrasives is to remove plaque and stain from teeth. There are various abrasive agents used in toothpastes. Almost 50% of toothpaste is made up of the abrasive agent. They are insoluble and help in plaque removal due to their abrasive action. These agents remove stains, polish the tooth surfaces and give a pleasing appearance to teeth.

Thickening / Binding agents:

These agents bind to water and control the viscosity of the toothpaste. They also prevent the toothpaste from drying out. They also give the toothpaste a creamy consistency. These agents have an emulsifying action, preventing the solid and the liquid substances from separating. These may be chemical compounds or natural plant or algae extracts.

Humectants:

Toothpastes may become dry when they come in contact with air. Humectants are short-chained polyalcohols, added in the toothpastes to prevent loss of water and thus preventing drying of toothpaste. They also provide a creamy texture to the toothpaste. Most frequently used humectants are glycerine and sorbitol.

Solvents:

Water acts as a solvent in toothpaste, allowing all the contents to dissolve and make a uniformly thick paste. In preparations like mouth rinses, alcohol is used as a solvent which, along with acting as a solvent, also acts as a taste enhancer.

Surfactants:

Surfactants or detergents are important components of toothpastes. They produce foam and aid in the removal of plaque and debris due to their surface action. These reduce the surface tension of the liquid environment in the oral cavity, thus allowing easy contact between toothpaste and teeth. These also have the ability to penetrate and dissolve plaque, making tooth cleaning easy. The surfactant also helps in dispersing the flavoring agent throughout the mouth, thus proving a feeling of …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Sweeteners:

These are added in the toothpaste to provide it a mild sweet taste. The commonly used sweeteners include sodium saccharin, sorbitol, and glycerin. Toothpastes made for children are usually made sweeter than that for adults. Xylitol is a sweetener that is also claimed to provide anti-caries activity.

Flavoring agents:

These are the essential oils which have the primary action of masking the bad taste of surfactants and other agents and also to give a pleasant flavor to the toothpaste. Most commonly used essential oils as flavoring agents are spearmint, peppermint, eucalyptus, and menthol. These are dissolved into the toothpaste with the help of surfactants. Various flavoring agents are added to the toothpastes by different companies, according to the demand from the customers.

Coloring agents:

These provide an attractive color to the toothpaste. The Color Index is used to classify the color of the coloring agent. Titanium oxide and chlorophyll are the most commonly used coloring agents in the toothpastes.

Preservatives:

Preservatives are added to the toothpastes to prevent the growth of microorganisms. The most commonly used preservatives are sodium benzoate, methylparaben, and ethylparaben.

Components of a toothpaste.
Abrasives
· Alumina · Aluminium trihydrate · Calcium carbonate · Sodium bicarbonate · Sodium metaphosphate · Calcium pyrophosphate · Pumice · Silica · Bentonite · Dicalcium phosphate · Hydroxyapatite · Kaolin · Methacrylate · Perlite (a natural volcanic glass) · Polyethylene · Zeolites
Surfactants
· Sodium lauryl sulfate (SLS) · Sodium N lauryl sarcosinate · Sodium stearyl fumarate · Sodium stearyl lactate · Sodium lauryl sulfoacetate · Amine fluorides · Dioctyl sodium sulfosuccinate
Humectants
· Water · Glycerol · Pentatol PPG (polypropylene glycol ethers) · Sorbitol · Xylitol · PEG 8 (polyoxyethylene glycol esters)
Thickening / Binding agents
· Carbopols · Sodium alginate · Sodium aluminum silicates · Carboxymethylcellulose · Silica thickeners Carrageenan · Hydroxyethylcellulose · Plant extracts (alginate, guar gum, gum arabic) · Algae extracts (Carrageenan and Carbomer) · Viscarine · Xanthan gum
Flavors
· Aniseed · Clove oil · Eucalyptus · Peppermint · Spearmint · Fennel · Vanilla · Menthol · Wintergreen
Preservatives
· Alcohols · Benzoic acid · Phenolics (methyl, ethyl, propyl) · Ethyl parabens · Formaldehyde · Methylparaben · Polyaminopropyl biguanide
Coloring agents
· Chlorophyll · Titanium dioxide
Sweeteners
· Acesulfame · Aspartame · Saccharine · Sorbitol
Therapeutic agents
Anti-caries agents · Fluoride · Xylitol · Calcium phosphate · Sodium bicarbonate Anti-plaque agents · Sodium Lauryl Sulfate (SLS) · Triclosan · Metal-ions · Amyloglucosidase and Glucose oxidase · Essential oils · Chlorhexidine Anti-calculus agents · Pyrophosphate · Zinc Anti-dentine hypersensitive agents · Potassium salts Anti-halitosis agents · Zinc Whitening agents · Abrasives · Dimethicone · Papain · Sodium bicarbonate

Therapeutic agents:

Various therapeutic agents can be added to impart a specific property to the toothpaste. The most commonly added therapeutic agent is fluoride, which prevents caries. Sodium fluoride (NaF) is most commonly used to make fluoridated toothpastes. Other agents used include mono-fluoro-phosphate (MFP) and stannous fluoride (SnF). The fluoride content in fluoridated toothpastes is between 0.10 – 0.15 %. Xylitol is another sugar alcohol, which cannot be fermented by oral microorganisms, hence is used as a cariostatic agent.

     The commonly added anti-plaque agent in toothpastes is triclosan. It is a synthetic non-ionic chlorinated phenolic agent with antiseptic qualities. It has an inhibitory effect on a broad spectrum of Gram-positive and Gram-negative micro-organisms. It acts on the cell membrane of the microorganisms and causes cell death due to leakage of cellular constituents. Other metal ions used as anti-plaque agents are zinc (Zn²⁺) and stannous (Sn²⁺) ions. These ions inhibit the glycolytic sequence in oral anaerobic bacteria, thereby inhibiting their growth. Certain enzymes such as amyloglucosidase and glucose oxidase are also used as anti-plaque agents. They inhibit the growth of microorganisms by activating the antibacterial lactoperoxidase-thiocyanate system in saliva ²⁴. Essential oils such as thymol, menthol, eucalyptol and methyl salicylate also have anti-plaque effects. They exert their antibacterial activity by altering the bacterial cell wall.

     Anti-calculus agents added to the toothpastes exert their anti-calculus action by delaying dental plaque calcification ²⁶. The commonly used anti-calculus agents are pyrophosphates (tetrasodium pyrophosphate, tetrapotassium pyrophosphate or disodium pyrophosphate). These have a high affinity towards the …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

     Anti-dentinal hypersensitivity toothpastes are becoming increasingly popular these days. The most common anti-dentinal hypersensitivity agents used in toothpastes are potassium ions. These act by blocking the open dentinal tubules, thereby blocking action potential generation in intradental nerves ²⁷.

     Tooth whitening toothpastes are also becoming popular these days. It must be noted here that no therapeutic agent can change the natural color of the tooth. These agents, which are added to toothpastes for tooth whitening primary prevent staining of the teeth and help in the elimination of extrinsic and to some extent intrinsic stains on the teeth. Dimethicones which are available in both high and low molecular weight polydimethylsiloxane fluids are commonly used as whitening agents. These impart a smooth surface to the tooth, thus preventing staining of teeth. Papain is another tooth whitening agent added to toothpastes. It is extracted from the Carica papaya plant. It has a property to hydrolyze peptide bonds, and catalyze the transfer of an acyl group. It does not have abrasive properties and is used as a non-abrasive agent for tooth whitening. Sodium bicarbonate is also a tooth whitening agent which exerts its action by removing intrinsic tooth stains.

     Zinc ions are added to the toothpastes for its anti-halitosis properties. Halitosis is due to the formation of volatile sulfur-containing compounds (VSC) by the action of bacteria present in the oral cavity on sulfur-containing amino acids as substrates. Zinc ions exert their anti-halitosis effect by interacting with sulfur in the amino acids or the metabolism of sulfur-containing amino acids.

     Toothpastes manufactured nowadays, serve multiple …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Mouth rinses

As already discussed, the use of mouth rinses for good oral health and elimination of bad breath can be dated back to centuries. They are less complex than toothpastes and are used as an adjunct to mechanical plaque control. The ideal properties of a mouth rise are,

It should significantly reduce plaque formation.
It should exhibit the property of substantivity.
It should eliminate the pathogenic microorganisms only.
It should be able to prevent the development of resistant bacteria.
It should not cause any adverse reaction with oral soft tissue.
It should not stain teeth or alter the taste sensation.
It should not react or have an adverse effect on dental materials.
It should be easily available, inexpensive and easy to use.

     In presently availably mouth rinse formulations, ethyl alcohol is the most commonly used ingredient which stabilizes certain active components of the mouth rinse and improves its shelf life. However, the use of alcohol in mouth rinses has been suspected to have a possible correlation with the development of oropharyngeal cancer 28. Accidental ingestion of alcoholic mouthwash by children may cause convulsions, brain damage, or coma. The alcohol in mouth rinses may also adversely affect the physical properties of certain restorations.

Sprays:

The spray is an effective way of delivering the therapeutic agent to a specific site. When applied accurately, sprays containing CHX have been used with almost equal efficacy as with CHX mouth rinses ^{29, 30}. These are useful in case of physically or mentally handicapped children.

Oral irrigators:

The oral irrigators are very useful in the elimination of plaque and debris from the periodontal pockets. These function by producing a water jet with pressure in continuous or pulsated mode, thereby eliminating plaque and debris. A detailed description of oral irrigators has been given in the previous chapter on mechanical plaque control. The oral irrigators have been used to deliver a variety of chemotherapeutic agents for plaque elimination. Various investigations have analyzed the efficacy of CHX irrigation in reducing plaque. In one investigation usage of 0.2% CHX digluconate in a pulsated jet irrigator as part of daily dental home-care measures was analyzed. The results of the study demonstrated that 0.2% CHX used twice daily in an oral irrigator was effective at reducing plaque deposition, periodontal inflammation and probing pocket depths 31.

      Another study by Lang et al. (1981) ³² compared the plaque reduction efficacy of CHX digluconate (0.05%) used as a mouth rinse and in oral irrigators during experimental gingivitis. The study showed that the fractionated jet irrigator delivering CHX digluconate was most effective in plaque reduction. These findings were supported by a two-month experimental study where 44 subjects with at least 6 interproximal sites which bled on probing were randomly distributed on a double-blind basis into 4 treatment groups. These groups were placebo-rinse, CHX-rinse (0.12%), placebo-irrigation and CHX-irrigation (0.06%). The parameters were recorded at baseline and at 60 days. The results of the study demonstrated that gingivitis was significantly reduced in the group using an oral irrigator delivering CHX (0.06%) ³³.

Varnish:

Various chemotherapeutic agents have been formulated in varnishes. These leave a thin layer of the active component on the applied surface which exerts its effect. CHX varnishes have been developed, however, their use is primarily restricted to prevent root caries rather than plaque control.

Let us now discuss various generations of chemical plaque control agents,

First-generation chemical plaque control agents

Phenols and essential oils:

Phenols and essential oils have a long history of use in the oral cavity as either mouth rinses or throat lozenges. The most well-known compound in this group is Listerine which has a long history of usage as an antiseptic agent. Listerine is made up of two phenol-related essential oils, thymol (0.064%) and eucalyptol (0.092%) mixed with menthol (0.042%) and methyl salicylate (0.060%), dispersed in a 21.6% – 26.9% hydroalcoholic vehicle. Many newer formulations have reduced alcohol content.

      The history of Listerine goes back to 1860’s when an English doctor, Sir Joseph Lister applied Louis Pasteur’s theory that infections are caused by invisible germs, and pioneered antiseptic surgery. In 1865, he became the first surgeon to carry out an operation in a chamber sterilized by pulverizing antiseptic in the air. The mortality rates in the patients were markedly reduced with this asepsis procedure. His work inspired Robert Wood Johnson and his brothers to start Johnson & Johnson to make the first sterile surgical dressings.

      Inspired by Lister’s work, Dr. Joseph Lawrence in 1879 originally formulated the Listerine formula and named this antiseptic “Listerine” in honor of Joseph Lister. This solution was used for cleaning surgical sites and irrigation of wounds which reduced the risk of infections following surgeries. By 1895, the use of Listerine in oral antisepsis was initiated and by 1914 it became the first mouthwash to be offered over the counter without a prescription. The initial study on antibacterial activity of Listerine was done by WD Miller, who studies its efficacy against oral bacteria. In his book “Microorganisms of the human mouth (1890)” ³⁴, he advocated the use of Listerine as a very useful antiseptic agent.

     Menaker et al. (1979) ³⁵ in a 21 days study compared plaque reduction in two groups of subjects where one group was given Listerine mouth rinse and another group was given a placebo agent. The authors reported 38-43% plaque reduction in the Listerine group as compared to other group using a placebo agent. In another study, Lamster et al. (1983) ³⁶ reported that twice-daily supervised rinsing with Listerine resulted in 22.2% in plaque and 28.2% reduction in gingivitis when compared to the placebo.

     These findings were supported by De Paola et al. (1989) ³⁷ who performed a 6 months study to test the anti-plaque and anti-gingivitis effects of Listerine as compared to hydroalcohol control, on developing plaque and gingivitis. The results of their study showed 34% reduction in plaque and gingivitis in the Listerine group as compared to 5% in the hydroalcohol control group. Fine et al. (1985) ³⁸ demonstrated a 50 to 60 % plaque reduction (by weight) with essential oil rinses in combination with …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

     However, when compared with CHX, essential oils are less efficacious in plaque reduction ^41-43. One study demonstrated a 25% reduction in plaque by Listerine as compared to CHX (0.12%) which showed 75% reduction in plaque ⁴¹. Other studies were done to compare the comparative efficacy of Listerine®, Meridaol (amine/stannous fluoride solution), and CHX under an experimental gingivitis situation ⁴⁴ and as an adjunct to routine oral hygiene ⁴⁵ over a period of 3 weeks. The results of the studies demonstrated that Listerine was only 50% as effective as CHX in supragingival plaque reduction and development of gingivitis.

     Triclosan, another phenol derivative which is chemically 2,4,4′-trichloro-2′-hydroxydiphenyl ether, has been used for years for making deodorants, soaps, and body powders. As with other phenolic compounds, it damages the bacterial cytoplasmic membrane, leading to the leakage of cellular components resulting in cell death. Its use as an anti-plaque agent has been studied and it has been shown to be 65% as effective as CHX ^{46, 47}.

     Triclosan is non-ionic as compared to CHX and is compatible with dentifrice ingredients. It does not possess good substantial substantivity, however; if it is mixed in special formulations, its substantivity is increased 48. These include zinc citrate or the co-polymer, polyvinylmethyl ether maleic acid formulations ⁴⁹. Triclosan is primarily used in …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Metal salts:

Silver nitrate, zinc chloride, and bichloride of mercury were among the heavy metal ions initially investigated for their anti-plaque activity ⁷. The use of silver and mercury compounds in the oral cavity is limited because of the effects like tooth staining and soft tissue and systemic side effects. Zinc is the most commonly used heavy metal ion as an anti-plaque agent. The anti-bacterial action of zinc is attributed to its inhibitory effect on the conversion of glucose to lactic acid by inhibiting enzymes of glycolysis in bacteria. Zinc ions also inhibit the enzymes required for glucose uptake by S. sanguis and S. mutans. It is used in the form of zinc lactate, zinc citrate, zinc sulfate or zinc chloride.

     Zinc ions have been shown to have good substantivity. It has been demonstrated in one study that following toothbrushing with toothpaste containing zinc citrate, approximately 30% of total zinc citrate is retained in oral cavity ⁵⁵. Gilbert and Ingramm (1988) ⁵⁶ in one study showed that after brushing with 1 gm toothpaste containing zinc, 38% of the zinc was retained in the oral tissues. Also, increased levels of zinc were observed in bacterial plaque and saliva. In another study on mouth rinse containing 0.5% and 1% zinc citrate, Gilbert et al. (1989) ⁵⁷ demonstrated an increase in the concentration of salivary zinc levels, which correlated with zinc citrate concentration in the mouth rinse.

     Another heavy metal compound used as an anti-plaque agent is stannous fluoride. It has been used in dentifrices and gels since 1940s. The anti-bacterial action of stannous fluoride is attributed to its adherence to the bacterial surface, inhibition of bacterial colonization, penetration into the bacteria cytoplasm and interference with the bacterial metabolism ⁵⁸. However, the major problem associated with its formulations is that it is not stable and its hydrolysis occurs in the presence of water ⁵⁹.

     The most commonly used stable combinations of stannous fluoride are stannous fluoride and amine fluoride and 0.454% stabilized stannous fluoride, which may or may not be combined with sodium hexametaphosphate (SHMP). In a review, various studies have been highlighted which have demonstrated beneficial effects of different SnF₂ formulations on the reduction in plaque accumulation and gingival inflammation ⁶⁰. The stannous fluoride formulations have been shown to …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Natural Products:

Various natural products have been used for their anti-plaque action in the oral cavity. These include sanguinaria extract, propolis, chamomile, sage, myrrh, echinacea, rhatany and peppermint oil.

Sanguinarine:

Sanguinarine is commonly used anti-plaque and anti-gingivitis natural product. Chemically, it is a benzophen-anthridine alkaloid derived from the alcoholic extraction of powdered rhizomes of the bloodroot plant, Sanguinaria canadensis ⁶³. Following alcoholic extraction and purification, an orange powder is obtained which contains 30–35% sanguinarine. The anti-bacterial activity of sanguinarine is attributed to the chemically reactive iminium ions. It has been demonstrated that its concentration of 16 µg/ml completely inhibited 98% of microbial isolates from human dental plaque ⁶⁴. Also, it acts synergistically with zinc ions to suppress the growth of various oral strains of Streptococci and Actinomyces ⁶⁵. It is retained in plaque several hours after its application in the oral cavity which accounts for its substantivity ⁶⁶. The anti-plaque action of sanguinarine has been extensively studied.

     In two reviews ^{7, 67} on the anti-plaque activity of sanguinarine, various short-term studies showed its variable but significant plaque inhibitory effects. However, all the studies agree on its anti-gingivitis effects. On the contrary, two other reviews of sanguinarine toothpastes, used alone without the mouthwash, demonstrated no significant reduction in plaque or gingival inflammation ^{68, 69}. Although, the majority of the studies have found the …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Propolis:

Propolis is a naturally occurring honeybee product, resinous in nature. Honeybees collect propolis from the buds and exudates of certain trees and plants and use it to seal openings in their hives ⁷³. It is a natural remedy and has been used extensively since antiquity. It was first used as an antiseptic, anti-inflammatory, antimycotic, and bacteriostatic agent by the Egyptians and then by the Greeks and Romans. The primary components of propolis are flavones, flavanones, and flavanols ^{74, 75}. The most effective flavonoid agents against bacteria are galangin, pinocembrin, and pinostrobin. Other chemicals in propolis, which contribute to its antibacterial action are ferulic acid and caffeic acid ⁷⁶.

     Its usage has been advised in multiple oral conditions such as in stomatitis, orthodontic traumatic ulcers, halitosis, periodontal pocket / abscess, as a mouthwash, in the treatment of dentinal hypersensitivity, lichen planus, candidal infections and angular cheilitis. It has also been used as a pulp capping agent, in the treatment of dry socket and pericoronitis ^77-82.

     The efficacy of propolis as an anti-plaque and anti-gingivitis agent has been investigated. The propolis extract has been used as a mouth rinse in many studies ^{73, 83-86}. Plaque inhibition by a propolis mouth rinse was compared to a positive and negative control in a double-blind, parallel, de novo plaque formation study design. CHX was significantly better in plaque inhibition as compared to propolis and the negative control group. The plaque inhibition in propolis group was marginally better than the negative control, but this difference was not significant ⁷³. Because of its low effectiveness in plaque inhibition, its use as anti-plaque mouth rinse is limited.

Fluorides

Fluorides primarily have anti-caries action. They do not possess anti-plaque or anti-gingivitis activity. However, stannous fluoride (SnF2) and amine fluoride demonstrate plaque inhibitory activity, particularly when they are combined together. Short-term studies have shown a significant reduction in plaque and gingival inflammation with the use of SnF₂ mouth rinse ^{87, 88}. However, long-term studies have demonstrated minimal beneficial effects of these agents in reducing plaque and gingivitis ^{89, 90}. Furthermore, the plaque inhibitory action of these agents is derived from the …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Antibiotics and Antimicrobial agents

The primary etiology of periodontal diseases is microbial. For this reason, the systemic and local use of antibiotics and antimicrobial agents has been a matter of discussion for a long time now 94. Antibiotics and antimicrobial agents are not indicated for the control of plaque and gingivitis, but they may be used as adjuncts in the treatment of other periodontal diseases. Three topical antibiotics have been evaluated for their anti-plaque and anti-gingivitis action. These are niddamycin, vancomycin, and kanamycin ^95-97. However, the side effects of these antibiotics and antimicrobials are of great concern when they are used for long term. Even when they are used locally, few side effects can be seen. Most important of these side-effects is the development of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) which may cause serious life-threatening infections.

Quaternary ammonium compounds

The quaternary ammonium compounds have been widely used in food, water treatment, and the textile industry because of their relatively low toxicity and broad antimicrobial spectrum. Cetylpyridium chloride (CPC) and benzalkonium chloride are the most studied compounds in this group. These compounds are moderate plaque inhibitors. They have a cationic surface by which they reduce the surface tension, get adsorbed to negatively charged surfaces and disrupt bacterial cell membrane. Because of their cationic nature, they bind strongly to plaque, oral mucosa and tooth surfaces but are released more rapidly as compared to CHX ^98-100. The substantivity of CPC has been estimated to be approximately 3-5 hours ¹⁰⁰. Their anti-bacterial action is reduced after their attachment to the oral tissues which may be due to the monocationic nature of these compounds.

     The CPC molecule has both hydrophilic and hydrophobic regions on its surface. The positively charged hydrophilic region is primarily involved in its antimicrobial activity. The interaction of the hydrophilic region with bacterial cell membrane disrupts its integrity which causes leakage of cytoplasmic components, interfering with cellular metabolism, inhibition of cell growth and cell death ^101-103. Two commercially available CPC preparations are Cepacol and Scope, with concentrations of 0.05% and 0.045% CPC, respectively. In addition to CPC, Scope contains 0.005% domiphen bromide.

     Various short and long term studies have evaluated the anti-plaque and anti-gingivitis properties of quaternary ammonium compounds. The short-term studies have reported an average plaque reduction of 35% with mixed effects on gingival health ^104-106. One six month trial investigated the anti-plaque and anti-gingivitis activity of CPC. The results of the study reported a …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

     Although, quaternary ammonium compounds have substantial anti-plaque and anti-gingivitis activity, but they are less efficient than CHX, which limits their use.

Oxygenating agents

Oxygenating agents such as hydrogen peroxide (H₂O₂) and buffered sodium peroxyborate and peroxycarbonate have been investigated for their use as anti-plaque and anti-gingivitis mouth rinses. Hydrogen peroxide has been used for a long time for cleaning the oral tissues, but its use an anti-plaque or anti-gingivitis agent is limited. Another problem with H₂O₂ is that it is unstable and difficult to formulate and store in concentration acceptable for human use (<3%). H₂O₂ is effective in the inhibition of anaerobic bacteria which are involved in the development of gingivitis and periodontitis ¹⁰⁹.

     Various short and long term studies have revealed unimpressive results with regard to their use as anti-plaque and anti-gingivitis agents ^110-113. Further, H₂O₂ in a concentration of 3% has been shown to increase the tissue injury in existing wound and delay wound healing, which raises its safety concern ^{114, 115}. Finally, the efficacy of H₂O₂ in a concentration of less than 3% in plaque and gingival inflammation reduction is less as compared to CHX, which limits its clinical use as a mouth rinse.

Enzymes

The enzymes used for anti-plaque activity can be divided into two categories: enzymes that disrupt the early plaque matrix and enzymes that enhance the host defense mechanism. The first group contains enzymes such as dextranase, mutanase and various other proteases which disrupt the plaque matrix. In the late 1960s and early 1970s, these enzymes were analyzed for their anti-plaque action. However, their poor substantivity and local side effects such as …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

     The second group of enzymes included glucose oxidase and amyloglucosidase that act to enhance the host defense system by catalyzing the synthesis of hypothiocyanite from thiocyanate through the salivary lactoperoxidase system. The hypothiocyanite has an inhibitory effect on the bacterial metabolism, thus exerting its anti-bacterial action. However, when hypothiocyanite was added to toothpaste and its clinical evaluation was done for its anti-plaque activity, the results were disappointing ^120-123. No long-term (6-month) studies are available to support the long term use of enzymes as anti-plaque or anti-gingivitis agents.

Surfactants/Detergents

Sodium lauryl sulfate (SLS) is the most common component of toothpastes and mouth rinse products. Because of its detergent action, SLS exerts its antimicrobial action by acting on the bacterial cell membrane ¹²⁴. SLS has moderate substantivity between 5 to 7 hours in the oral cavity which is almost similar to triclosan ^{124, 125}. Mouth rinses containing only SLS are not available commercially and there are no long-term studies supporting their usage for a long duration.

Second-generation chemical plaque control agents

Bisbiguanides:

Bisbiguanides are a class of chemically related organic compounds which are known for their bactericidal properties. This group of chemical compounds contains agents like chlorhexidine, alexidine, and octenidine. CHX is presently the most widely used anti-plaque and anti-gingivitis agent. Read “Chlorhexidine” for details.

Third-generation agents

Delmopinol:

Delmopinol is a low molecular weight, surface-active compound which is chemically, 3-alkyl substituted N-hydroethyl morpholine. It belongs to the amine alcohols and the other agent in this group is octapinol. Delmopinol has demonstrated good potential as a mouth rinse for the management of dental plaque and treatment of gingivitis. Its mechanism of action is through inhibition and disruption of the biofilm extracellular matrix. In other words, it is not an …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

     The substantivity of delmopinol is less as compared to CHX. In one study the antibacterial activity of delmopinol was estimated to be only 30 minutes as compared to several hours for CHX ¹⁶³. The anti-plaque and anti-gingivitis effects of 0.1% and 0.2% delmopinol hydrochloride mouth rinses were studied in one clinical investigation where 450 healthy subjects with moderate levels of plaque and gingivitis were involved in the study. They were told to use Delmopinol mouth rinses or a placebo mouth rinse twice a day after brushing. All the groups demonstrated decreased plaque, gingivitis, and calculus scores. Anti-plaque results were in favor of 0.2% delmopinol with slight significance.

     The side effects observed in the patients included transitory numbness of the tongue, staining of teeth and tongue, taste disturbance and rarely mucosal soreness and erosion ¹². Another study showed that daily rinsing of 0.1%, 0.5% and 1% of delmopinol reduced 16%, 56% and 56% of mean plaque extension and significantly reduced the mean gingival index when compared to the placebo ²⁰⁵.

     When compared with 0.2% CHX, 0.2% delmopinol showed a comparable reduction in plaque scores. However, the reduction in gingivitis was similar to that of placebo mouth rinse, doubting its anti-gingivitis efficacy ²⁰⁶. Delmopinol has been incorporated in various products such as mouthwash, sprays, toothpastes and lozenges. The major side effect associated with long-term use of delmopinol is transient tingling and numbness of the tongue or other parts of the oral mucosa ^206-208.

Other agents

Salifluor:

Chemically, salifluor is 5 N-oetanoyl-3’trifluormethylsalieyl-anilide. It is a broad-spectrum antimicrobial agent and has been investigated for its ability to inhibit dental plaque formation. It has demonstrated excellent activity against a wide variety of Gram-positive and Gram-negative oral microorganisms, including Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Tenerella forsythia ²⁰⁹. Salifluor also possesses anti-inflammatory properties ²¹⁰. However, the mechanism involved in the anti-microbial and anti-inflammatory properties of salifluor has not been …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Povidone-iodine

Iodine has been used for centuries in wound care. Theophrastus, Aristotle’s pupil, was the first one to describe the application of seaweeds and other plants rich in iodine to relieve pain after sunburn wounds ²²⁵. Wounded soldiers were first treated with plants enriched with iodine during Napoleon’s Egyptian campaign. During the American Civil War, Davis (1839) ²²⁶, also reported using iodine to treat wounds. Despite the use of iodine-rich plants for the treatment of wounds for centuries, iodine as a natural element was not discovered until 1811 by Bernard Courtois, a chemist.

     The name iodine comes from the Greek word, “iodides”, that means ‘violet colored’, because of the violet color of iodine vapors. It is a dark non-metallic crystalline solid that belongs to the halide group of elements in the periodic table. After isolation of iodine, its aqueous and alcoholic solutions were formulated but they were found to be …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

     Povidone-iodine or polyvinylpyrrolidone iodine complex (PVP-I) is a combination of molecular iodine and polyvinylpyrrolidone surfactant/iodine complex. It contains from 9.0% to 12.0% available iodine, calculated on a dry basis. The bactericidal agent is povidone-iodine is free iodine (approximately one part per million) which directly causes in vivo protein denaturation, precipitation of bacteria, and further resulting in the death of pathogenic microorganisms ^{227, 228}. It specifically attacks amino acids, which are essential for bacterial survival (free sulfur amino acids cysteine and methionine). It also destroys bacterial nucleotides and fatty acids causing cell death. The anti-viral action of iodine has been less elucidated. The povidone-iodine aqueous solution has strong pharmacological activity against Staphylococcus aureus, Neisseria gonorrheae, Pseudomonas aeruginosa, syphilis, hepatitis B virus, HIV, and Trichomonas vaginalis ^{227, 229}.

Iodine formulations:

The most widely used formulation of povidone-iodine is its 10% solution in water for application as paint, spray, or wet soak. Other formulations include a 7.5% concentration scrub with detergent for pre-operative and post-operative scrubbing and a germicidal wash, and 5% water-soluble first aid cream, and a 10% water-soluble ointment.

Povidone-iodine mouth rinses:

Povidone Iodine preparation, 1.0% w/v (equivalent to 0.1% w/v of available iodine), is widely used as a mouth rinse. It is commonly used mouth rinse in case of oral infections, including aphthous ulcers, gingivitis, stomatitis, and pharyngitis due to superficial infections. It is used for oral hygiene prior to, during and after oral surgery. It is used to gargle or rinse the mouth for up to one minute and should not be swallowed. It should not be used for more than 14 days, particularly in patients with …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book …….. Contents available in the book ……..

Hydrogen peroxide (H₂O₂)

As already discussed, H₂O₂ has been used for a long time as mouth wash. It is an oxidative agent and destroys bacteria via oxidation damage. It generates free-radicals, which destabilize the molecular structure and cellular strength of the bacteria cell wall, resulting in cell death. 1.5% solution of H₂O₂ is commonly used as mouthwash. In high concentration it is also used in teeth bleaching agents to whiten the teeth. It should be remembered that long term use of H₂O₂ is not recommended because of the side effects associated with it including cytotoxic effect on the dental pulp cells and potential carcinogen ^{230, 231}.

General indications for mouth rinses

Oral malodor:

The most common indication for the use of mouth rinses is oral malodor. Many chemical plaque control agents such as CHX, CPC, essential oils, triclosan etc. reduce the volatile sulfur-producing bacteria in the oral cavity, thus reducing oral malodor. These agents must be differentiated from mouth fresheners which do not kill the microorganisms causing malodor.

Anti-plaque agents:

Although, mechanical plaque control is the primary method for controlling plaque accumulation, chemical plaque control agents may be used as an adjunct to mechanical plaque control. It must be remembered that chemical plaque control agents should not be advised to each and every patient. Those patients, who are not able to maintain an adequate oral hygiene due to any reason or patients with periodontal diseases, may be advised to use these agents. The most commonly used anti-plaque agent is CHX.

Anti-gingivitis agents:

Gingivitis is the result of plaque accumulation and resultant inflammation due to host-bacterial interaction. Adequate mechanical plaque control is the primary measure to reduce gingivitis. However, some mouth rinses may be advised to the patient to control gingival inflammation, including essential oils (Listerine), CHX etc.

Calculus control:

In high calculus formers, agents which reduce the calculus formation are useful. These contain ingredients like zinc chloride, which retards calculus formation.

Anti-caries:

Patients with high caries risk may get benefited from the use of mouth rinses congaing fluorides. Fluoride preparations such as sodium fluoride, acidulated phosphate, stannous fluoride or combination of fluoride sources may be advised in these patients.

Conclusion

Chemical plaque control measures are widely used for controlling plaque formation and preventing the development of gingival inflammation. Dentifrices are the most commonly used chemical plaque controlling agents, used in combination with tooth-brushing. Along with providing clean teeth, they also provide fresh breath. The therapeutic agents added in dentifrices also help in reducing incidences of caries and periodontal diseases. Mouth rinses are commonly used for the prevention of halitosis with CHX formulations being the most commonly available over the counter mouth rinses world-wide. Although various mouth rinses have shown their anti-plaque and anti-gingivitis effects, they cannot be used alone as monotherapy to control plaque but are used in conjunction with mechanical plaque control. The regular use of mouth rinses is associated with some side effects. Presently, CHX is considered as gold standard for chemical plaque control, but it does not fulfil all the qualities of an ideal anti-plaque and anti-gingivitis agent. More research is required to formulate a chemical plaque control agent which is better than CHX and fulfills most of the requirements if not all, of an ideal chemical plaque control agent.

References

References are available in the hard-copy of the website.

Suggested reading

1. Moran JM. Chemical plaque control–prevention for the masses. Periodontology 2000. 1997 Oct;15(1):109-17.
2. Addy M, Moran JM. Clinical indications for the use of chemical adjuncts to plaque control: chlorhexidine formulations. Periodontology 2000. 1997 Oct;15(1):52-4.
3. Solheim H, Eriksen HM, Nordbø H. Chemical plaque control and extrinsic discoloration of teeth. Acta Odontologica Scandinavica. 1980 Jan 1;38(5):303-9.
4. Hull PS. Chemical inhibition of plaque. Journal of Clinical Periodontology. 1980 Dec;7(6):431-42.
5. Cummins D. Routes to chemical plaque control. Biofouling. 1991 Aug 1;4(1-3):199-207.
6. Sugano N. Biological plaque control: novel therapeutic approach to periodontal disease. Journal of oral science. 2012;54(1):1-5.
7. Herrera D. Cetylpyridinium chloride-containing mouth rinses and plaque control. Evidence-based dentistry. 2009 Jun;10(2):44-.
8. Newman HN. The rationale for chemical adjuncts in plaque control. International dental journal. 1998 Jun;48(S3):298-304.
9. Newman HN. Modes of application of anti‐plaque chemicals. Journal of clinical periodontology. 1986 Nov;13(10):965-74.
10. Mandel ID. Chemotherapeutic agents for controlling plaque and gingivitis. Journal of clinical periodontology. 1988 Sep;15(8):488-98.