Anti plaque agents, Dr Sai Lakshmi

anti plaque agents, plaque reducing agents, plaque control, chemical plaque control

1. ANTI-PLAQUE AGENTS Presented By- Dr Sai Lakshmi Dept. of Periodontology, NDCH

2. CONTENTS Glossary of terms Introduction History Rationale of antiplaque agents Classification of antiplaque agents Ideal properties of Antiplaque agents Groups of agents used in antiplaque agents - Bis-biguanide Quaternary ammonium compounds Phenols and essential oils Natural products Enzyme preparations Oxygenating agents Antibiotics Anti-calculus agents Metal salts Amine alcohols Chelating agents Anti-microbials Urea Bisphosphonates Victamine C Pyrophosphates Polymers & Copolymers Conclusion References

3. GLOSSARY OF TERMS A nti-plaque agent : defined as the chemical that have an effect on plaque sufficient to benefit gingivitis and/or caries. Anti-gingivitis agent : defined as the chemical which reduce the gingival inflammation without necessarily influencing bacterial plaque. Antimicrobial agents : chemicals that have a bacteriostatic or bactericidal effect in vitro that alone cannot be extrapolated to a proven efficacy in vivo against plaque.

4. Plaque reducing/inhibitory agents : 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. Antiseptic : An agent that inhibits the growth and development of microorganisms Antibiotic : Molecules or agents produced by microorganisms that have the capacity to kill or inhibit the growth of other microorganisms. Bacteriostatic : Inhibiting or retarding the growth of bacteria.

5. Dentifrice : A preparation intended to clean and polish the teeth. Active ingredients to prevent caries and plaque accumulation or to desensitize teeth may be included. Gram-positive : Pertaining to bacteria that stain deep purple with Gram stain. These bacteria have a thick peptidoglycan layer but no lipopolysaccharide in their cell walls. Gram-negative : Pertaining to bacteria that counter stain pale red with Gram stain. These bacteria have a lipopolysaccharide (endotoxin) layer exterior to a thin peptidoglycan layer in their cell walls. Gingivitis : Inflammation of the gingiva.

6. Introd u ction Plaque: Plaque is defined clinically as a structured, resilient, yellowish - grayish substance that adheres tenaciously to the intraoral hard surfaces, including removable and fixed restorations.

7. Materia alba: refers to soft accumulations of bacteria and tissue cells that lack the organized structure of dental plaque and it is easily displaced with a water spray. Calculus : Calculus is a hard deposit that forms by mineralization of dental plaque and it is generally covered by a layer of unmineralized plaque.

8. HISTORY Usage of the chemical products dates back to 6000 years Ebers papyrus – 1500 BC – recipes for tooth powders Mouth rinses - 4000 BC In 2700 BC – mouth should be rinsed with child’s urine (European writings) Honey, wine and vinegar have also been used as plaque control agents Hippocrates – used dentrifice Use of tooth pastes can be attributed to chemo parasitic theory of tooth decay by W. D. Miller in 1890.

9. PLAQUE CONTROL Mechanical plaque control: with the help of tooth brush, dentrifices, interdental cleaning aids, gingival massage, oral irrigators. Chemical plaque control: with the help of antiplaque and anti-calculus agents.

10. Chemical plaque control – Rationale Gingivitis & periodontitis are highly prevalent diseases and prevention of occurrence or recurrence is dependent on supragingival plaque control. Mechanical tooth cleaning through toothbrushing with tooth paste is the most common method of oral hygiene practiced. Tooth cleaning is largely influenced by the compliance and dexterity of the individual.

11. Improving oral hygiene & gingival health – Decreasing incidence of perio dontal disease ( Hugoson et al 1998) Tooth cleaning is largely influenced by compliance & dexterity of individual Individual brushing 2 mins – only around half of plaque removal (de la Rosa et al 1979) The concept of chemical plaque control can be justified as a means of overcoming inadequacies of mechanical cleaning.

12. Long term periodontal T/t follow up – success dependent on maintaining plaque levels ( Axelsson & Lindhe , 1981) Mechanical plaque control aims – maintaining plaque level quantitatively/ qualitatively compatible with health & not bacteria - free To overcome deficiencies in mechanical tooth cleaning - adjunctive use of chemicals

13. Approaches to chemical supragingival plaque control Action of chemicals would fit into four categories:

14. Anti-adhesive agents would act at the pellicle surface to prevent the initial attachment of the primary plaque-forming bacteria. These agents act most effectively on an initially clean tooth surface and such chemicals prevent the attachment and development of a variety of biofilms and are usually described as antifouling agents. Eg: Anionic polymers, substituted alcohols ANTI – ADHESIVE AGENTS

15. Antimicrobial agents could inhibit plaque formation through two mechanisms. The first would be the inhibition of bacterial proliferation at the pellicle on the primary plaque forming bacteria. The second effect could be bactericidal, where by the antimicrobial agent destroys all of the microorganisms either attaching or already attached to the tooth surface. Eg: Chlorhexidine ANTI – MICROBIAL AGENTS

16. These agents are given the terminology as “chemical tooth brush” because the agent contained in the mouth rinse would be expected to reach all tooth surfaces and totally effective in the oral cavity. Eg: hypochlorites and enzymes PLAQUE REMOVAL AGENTS

17. These agents act on plaque microorganisms which might inhibit the expression of their pathogenicity without necessarily destroying the microorganisms. These are compared to anti microbial agents which exert such action through bacteriostatic mechanism to achieve such results. ANTI – PATHOGENIC AGENTS

18. Vehicles for the delivery of chemical agents: The carriage of chemical agents into the mouth for plaque control has involved a small but varied range of vehicles. They are 

19. Tooth paste It is the ideal vehicle for the carriage of plaque control agents. A number of ingredients go to make up toothpaste and each has a role in either influencing the consistency and stability of the product or its function.

20. Abrasives like Silica, alumina, dicalcium phosphate, and calcium carbonate either alone or more usually in combination are used. Detergents like sodium lauryl sulfate, which imparts the foaming and “feel” properties to the product. Additionally, detergents may help dissolve active ingredients and the anionic detergent sodium lauryl sulfate has both antimicrobial and plaque inhibitory properties. Thickeners, such as silica and gums, primarily influence the viscosity of the product.

21. Sweeteners, includes saccharine Humectants, notably glycerin and sorbitol to prevent drying out of the paste once the tube has been opened. Flavors, of which there are many but mint or peppermint are popular in the western world although rarely found in the toothpaste in the Indian subcontinent where herbal flavors are more popular. Actives, notably for caries prevention; for plaque control triclosan and stannous fluoride.

22. Mouth rinses Mouth rinses vary in their constituents but are usually considerably less complex than toothpastes. They can be simple aqueous solutions. But to be stable, they should be added with flavoring agents, coloring agents and preservatives like sodium benzoate. Anionic detergents are included in some products but, again, cannot be formulated with cationic antiseptics such as cetylpyridinium chloride or chlorhexidine. Ethyl alcohol is commonly used both to stabilize certain active ingredients and to improve the shelf-life of the product.

23. Sprays Sprays have the advantage of focusing delivery on the required site. The dose is clearly reduced and for antiseptics such as chlorhexidine this has taste advantages . When correctly applied, chlorhexidine sprays were as effective as mouth rinses for plaque inhibition, although there was no reduction in staining. Chlorhexidine sprays were particularly useful for plaque control in physically and mentally handicapped groups.

24. Irrigators Irrigators were designed to spray water, under pressure, around the teeth. As such they only remove debris, with little effect on plaque deposits. Antiseptics and other plaque control agents, such as chlorhexidine, have been added to the reservoir of such devices.

25. Chewing gums chewing gums appear to have little effect in the plaque control particularly at sites prone to gingivitis and they can reduce occlusal plaque deposits.

26. Varnishes Varnishes have been employed to deliver antiseptics including chlorhexidine, but the purpose has been to prevent root caries rather than as a reservoir for plaque control throughout the mouth.

27. Uses of antiplaque agents To replace mechanical tooth brushing when it is not possible in situations like: - After oral or periodontal surgery during the healing period. - After intermaxillary fixation used to treat jaw fractures. - With acute oral mucosal or gingival infections when pain & soreness prevents mechanical oral hygiene. - For mentally or physically handicapped patients who are unable to brush their teeth.

28. As an adjunct to normal mechanical oral hygiene in situations where this may be compromised by discomfort or inadequacies: - Following sub-gingival scaling & root planing when gingivae may be sore for a few days. - Following scaling when there is hypersensitivity due to root exposure. - Following scaling when patient’s oral hygiene remains inadequate.

29. IDEAL PROPERTIES

30. Classification of Antiplaque agents

31. Classification of Antiplaque agents Antiadhesives Antimicrobial Plaque removal Antipathogenic 1. Mechanism of action

32. Bisguanides: chlorhexidine, alexidine, octanidine Quarternary ammonium compounds: benzalkonium chloride, cetylpyridinium chloride Phenols and essential oils: Listerine Fluorides: sodium fluoride, stannous fluoride, organic amine fluoride 2. chemical nature Antiseptics: iodine, povidone iodine, chloramine Antibiotics: penicillin, tetracycline, vancomycin, spiramycin , kanamycin, streptomycin, actinomycin, erythromycin, bacitracin etc. Oxygenating substances: hydrogen peroxide, buffered sodium peroxyborate

33. Enzymes: protease, amylase, mutanase , amyloglycosidase , glucose oxidase and amyloglucosidase Plant alkaloid: sanguinarine Metal ions: Zn, Cu, Sn Triclosan Other agents: salifluor , delmopinol, detergents, propolis, etc. 3. form Mouthrinses Sprays Irrigators Chewing gums Varnishes

34. BIS-BIGUANIDES Several bisguanides possess antiplaque activity, including chlorhexidine, alexidine, octenidine. However, chlorhexidine is the most studied and used. Are primarily second generation anti-plaque agents as they exhibit considerable substantivity and have broad antibacterial properties Most effective anti-plaque agents currently in use are as follows:

35. CHLORHEXIDINE Chlorhexidine- the digluconate of chlorhexidine is a synthetic antimicrobial which was developed in late 1940’s. Loe & Schiott introduced this agent as an oral antimicrobial agent (0.2%) and have shown that 5, 2 and even 1 daily rinse, prevented plaque accumulation and development of gingivitis, over a 21 day period of no oral hygiene. Clinical studies of several months duration have reported plaque reductions of 45% to 61% and gingivitis reductions of 27% to 67%.

36. MECHANISM OF ACTION: Chlorhexidine is a base and is stable as a salt. The most common preparation is chlorhexidine digluconate that is water soluble and at physiologic pH it readily dissociates releasing the positively charged chlorhexidine component. Access to the bacterial cell wall is enhanced by the electrostatic force between positively charged chlorhexidine cations and negatively charged lipoteichoic acid and other components of bacterial cell wall, thereby altering the osmotic equilibrium. Having gained access to the inner cell membrane, chlorhexidine disorientates its lipoprotein structure causing destruction of the osmotic barrier and resulting in the leakage of intracellular components.

37. At low concentrations of chlorhexidine, small molecule weight substances such as potassium and phosphorus will leach out, exerting a bacteriostatic effect. At high concentrations of chlorhexidine, bactericidal effect occurs due to precipitation and coagulation of cytoplasm. Bactericidal effect is thought to be less important than the bacteriostatic effect, provided by the slow release of chlorhexidine. Chlorhexidine is more effective in preventing plaque accumulation on a clean tooth surface than in reducing pre-existing deposits.

38. In addition to antibacterial properties, chlorhexidine also reduces bacterial colonization on tooth surface by 3 mechanisms: The effective blocking of acidic group of salivary glycoproteins will reduce their adsorption of hydroxyapatite and formation of acquired pellicle. The ability of bacteria to bind to the tooth surface may also be reduced by the adsorption of chlorhexidine to the extracellular polysaccharides of their capsules or glycocalyces. Chlorhexidine may compete with Calcium ions for acidic agglutination factors in plaque.

39. SPECTRUM OF ACTIVITY: Chlorhexidine has broad spectrum of activity and is effective against a wide variety of gram + ve and gram - ve organisms, yeasts and fungi. Gram + ve organisms are more sensitive than gram - ve organisms and streptococci are more sensitive than staphylococci. Rinsing with 10ml of 0.2% chlorhexidine for 1 min. has resulted in suppression of new plaque deposits. Salivary bacterial counts taken immediately after rinsing with 0.2% solution demonstrated a 80% to 90% reduction of organisms. Subsequent to cessation of drug application salivary count of organisms return to baseline value within 48hrs.

40. SUBSTANTIVITY OF CHLORHEXIDINE: The ability of the drug to absorb onto or bind to the soft and hard tissues is known as substantivity. Substantivity of chlorhexidine was first described in 1970’s. What gives chlorhexidine its advantage over many other agents is its ability to bind strongly to many sites in the oral cavity. It is this substantivity that enables it to function as a form of slow release device and maintain an ongoing rather than intermittent antibacterial action. The proportion of chlorhexidine retained is directly dependent upon concentration, volume and pH in the mouth.

41. SAFETY OF CHLORHEXIDINE: Animal experiments have shown that primary route of excretion is through feces. It is poorly absorbed by the GIT and therefore displays very low toxicity. No evidence of carcinogenic or teratogenic alterations has been found.

42. SIDE EFFECTS: Flotra et al. 1971 Brown discoloration of teeth, some restorative materials & dorsum of tongue Lang et al. 1988 2. Taste perturbation where salt taste appears to be preferentially affected & leave food and drinks with a rather bland taste

43. 3. Oral mucosal erosion – idiosyncratic reaction and concentration dependent, d ilution of 0.2% formulation to 0.1%, but rinsing with whole volume to maintain dose, usually alleviates problem

44. Enhanced supragingival calculus formation – may be due to precipitation of salivary proteins on to tooth surface - increasing pellicle thickness &/or precipitation of inorganic salts on to or into pellicle layer Chx also has a b itter taste - difficult to mask completely

45. Oral hygiene and gingival health benefits in mentally & physically handicapped Medically compromised individuals predisposed to oral infections High-risk caries patients Adjunct to oral hygiene & professional prophylaxis Post oral surgery including periodontal surgery or root planing For patients with jaw fixation CLINICAL USES

46. Denture stomatitis Removable and fixed orthodontic appliance wearers Recurrent oral ulceration Immediate pre-operative chlorhexidine rinsing and irrigation Oral malodour Sub gingival irrigation

47. CLINICAL USAGE: It is accepted by FDA and ADA. Available as mouthwash- 0.2% chlorhexidine, recommended as 10ml per rinse and 0.12% chlorhexidine recommended as 15 ml per rinse. Available as gel (1%). It is more difficult to incorporate chlorhexidine into toothpastes because of binding of chlorhexidine to components in the toothpaste .

48. Reviews : Holbeche JD et al. 1975 , conducted a study with commercially available mouthwash, containing 0.05 per cent w/v cetylpyridinium chloride. This CPC mouth rinse reduced dental plaque accumulation by 30 per cent in a clinical trial when used briefly, three times a day, after meals.

49. Moran J et al. 1991, conducted an active/placebo parallel group design to evaluate the use of a CPC mouth rinse as an adjunct to oral hygiene when used before tooth brushing. Plaque and gingivitis scores were recorded at baseline and after 6 weeks, following twice daily use of the active or placebo pre-brushing rinses. Plaque and gingivitis were significantly reduced at 6 weeks in both groups with no significant treatment differences between the active and placebo formulations.

50. Quaternary ammonium compounds Quaternary ammonium compounds such as cetyl -pyridinium chloride have moderate plaque inhibitory activity. Although they have greater initial oral retention and equivalent antibacterial action to chlorhexidine but they are less effective than chlorhexidine in inhibiting plaque and gingivitis. One reason for this may be that they are readily desorbed from the oral mucosa.

51. Phenols and essential oils Phenols, either alone or in combination, have been used as mouthrinses or lozenges. Most phenols exert a non-specific action which is dependent upon the ability of drug. In its non-ionized form, it penetrates through the lipid component of the cell walls of gram - ve organisms and denatures the bacterial proteins. Listerine is an essential oil/phenolic mouthwash which has been shown to have moderate plaque inhibitory effects and some anti-gingivitis effects. It has been accepted by ADA to be an aid to home oral hygiene procedures.

52. Goodson et al (1985) demonstrated that after 9 month application of Listerine, there was a reduction of nearly 80% in plaque toxic activity. Phenolic compounds are also known as scavengers of oxygen free radicals and hence should have an effect on leucocyte activity. Adverse effects are minimal and safety has been established by quite long clinical use. Some patients find an initial burning sensation and bitter taste. Occasional staining of minimal amount has been found.

53. Triclosan, a trichlor-2-hydroxydiphenyl ether, is a non-ionic antiseptic which lacks the staining effects of cationic agents. It has been used recently in a number of commercial mouthwashes and toothpastes. It ha a broad antibacterial properties and moderate antiplaque properties when used in combination with zinc. It has been found to retain in mouth and to have clinical efficacy without side effects.

54. The primary site of action is bacterial cellular membrane of bacteria. At bacteriostatic conc., triclosan prevents the uptake of essential amino acids. At bactericidal conc., it causes disorganization of the cellular membrane and leakage of cellular contents. Triclosan itself has little or no substantivity, its substantivity can be increased by its combination with copolymers of methoxy ethylene and maleic acid ( Gantrex , ISP corps ).

55. Despite its more rapid clearance, triclosan has been shown to be present in an elevated level in plaque and saliva for 8 hrs. and in the oral mucosa for 3 hrs. after tooth brushing. There is evidence that triclosan may also act as an anti-inflammatory agent in mouthrinses and toothpastes. Anti-gingivitis effect of triclosan is due to its anti-inflammatory property.

56. Brecx M, Brownstone E, Mac Donald L et al. 1992, conducted a study to compare the anti-plaque, anti-gingivitis and anti-microbial efficacies of a phenolic compound (Listerine) and 2 different amine/stannous fluoride mouthwashes (Meridol I, II) when these solutions were used in addition to usual tooth cleaning. A placebo preparation was utilized as a negative control and a chlorhexidine solution as a positive control in this double blind study. This study has demonstrated that a combination of habitual self-performed and non-supervised oral hygiene with Meridol or Listerine is more beneficial for plaque control than the use of mechanical oral hygiene alone.

57. Sekino S et al. 2005, conducted a study to test the clinical effect of Listerine, a mouth rinse containing a mixture of phenolic compounds, is ascribed to its bactericidal properties. However, phenolic compounds are also known to interfere with the inflammatory process. Results have shown that the effect of Listerine on gingivitis is more pronounced than on plaque formation. This indicates that the phenolic compound may have anti-inflammatory effects.

58. Plant / Benzophenanthridine alkaloid BPA was believed to be the active ingredient in tooth cleaning sticks used by the native cultures in Africa. The active ingredient is Sanguinarine. Sanguinarine has been isolated from the alcoholic extract of powdered rhizomes of the blood root plant, Sanguinaria candensis .

59. Sanguinarine contains the reactive iminium ions, these ions are retained in the plaque for several hours after use. Sanguinarine has cationic nature and acts by inhibiting thiol dependent enzymes. Acts partly by interfering with the membrane bound metallic constituents, reducing glycolysis and inhibiting the adherence of oral bacteria. Sanguinarine appears to an effective plaque inhibitory agent but is less effective than chlorhexidine in this regard.

60. Also unlike chlorhexidine it is not able to prevent the development of gingivitis. Mouthwash is much more effective than toothpaste. This may be due to binding of other components in the toothpaste to the chemically reactive site of sanguinarine. Commercial available mouthrinse contains sanguinarine in Zn ions- Viadent (0.03% Sanguinarine Zn chloride).

61. Parsons LG et al. 1987 , conducted a study to evaluate Sanguinaria extract (sanguinaria) solutions in 44 subjects in a 2-week study as a 300 µg/ml manual rinse and a supragingival irrigation with 22.5 mg/ml sanguinaria and supragingival irrigation with water. Both the manual use of sanguinaria and supragingival irrigation of dilute sanguinaria produced significantly less plaque growth than supragingival irrigation with deionized water. It was shown that dilute solutions of sanguinaria delivered via rinsing or supragingival irrigation are effective in controlling plaque as an additional benefit to the use of supragingival irrigation to control gingivitis.

62. Kopzyk RA et al. 1991, conducted a study to test the efficacy and safety of sanguinaria-containing regimens with and without fluoride. The study was a 6-month, double-blind, 4-cell, placebo-controlled, parallel investigation involving 120 subjects. Following screening procedures, subjects were randomly assigned to 4 groups and the study was implemented on them as per the procedure. Supragingival plaque and gingival inflammation were scored at 0, 1, 2, 1.5, 3, 4.5, and 6 months. Microbiological samples were taken from plaque, tongue, and cheek areas. GI, PI and BOP scores were lesser in sanguinaria group.

63. Enzyme preparations The rationale of using enzymes as active agents in antiplaque preparations was that they would be able to break the matrix of already formed plaque and calculus. Furthermore, it was accepted that certain proteolytic enzymes would be bactericidal to plaque microorganisms. However, clinical trials on animals and humans have been disappointing. The initial efforts during 1950-1970 were to employ enzymes directly to degrade the intercellular matrix and plaque integrity.

64. The following preparations were tested: Preparation of dehydrated pancreas ( Viokase ) Mucinase Protease-amylase Fungal enzymes Dextranase Mutanase All these preparations are of historic interest and they are not in use now.

65. Oxygenating agents H2O2, sodium peroxyborate, peroxycarbonate are useful in ANUG . Further investigations are required for these substances to act as antiplaque agent.

66. Antibiotics Penicillin, Vancomycin, Nindamycin and Kanamycin have been used for antiplaque activity. All of these reduce significant amount of plaque formation. Potential problem with their use is of bacterial resistance. Hypersensitivity reaction on topical application are common. The potential benefit of using long term antibiotics is less than harm.

67. Collaert B et al. 1992, conducted a study to investigate a possible dose-response effect of delmopinol hydrochloride, on the development of plaque and on the healing of gingivitis. 64 healthy male volunteers, aged 18-40 years with healthy gingivae and clean teeth, participated. During a 2-week period, the participants refrained from all oral hygiene and rinsed 2x daily with a placebo solution. On day 14 of the study, they received professional teeth cleaning, and were randomly assigned to 4 groups.

68. No oral hygiene procedures were performed during the test period. On days 0, 14 and 28, gingival bleeding index and the presence of stainable plaque were determined. Periodic identical photographs were used for planimetric determination of buccal plaque extension. No significant difference for the reduction in gingival bleeding index was found between 0.2% delmopinol and chlorhexidine rinsing. A significant dose-response effect for 0.05%, 0.1% and 0.2% delmopinol was found for gingival bleeding index, plaque index and plaque extension. The results show that delmopinol favors the healing of gingivitis and reduces plaque formation.

69. However, there was a significant reduction in the proportion of dextran-producing streptococci in the active groups compared to the control group throughout treatment. There was no colonization by Candida or Gram-negative aerobic bacilli in the active groups nor was there any decrease in susceptibility to delmopinol. Delmopinol appears to mediate its anti-plaque effect without causing a major shift in bacterial populations, although dextran-producing bacteria appear to be affected, which may have relevance to this agent's mode of action.

70. Metallic salts Mainly Zn, Sn, Cu salts are having antiplaque and anti-calculus activities. At high concentration they can be bactericidal. At sublethal levels: can inhibit plaque growth by altering the surface potential of plaque bacteria thus reducing the rate of bacterial deposition onto the teeth. can inhibit a number of enzyme systems relating to carbohydrate metabolism. can cause proteolysis. Zn citrate ( 0.5%, 1% ) has been utilized for years as antiplaque and anticalculus agent. In the laboratory, it can inhibit acid production by oral streptococci and trypsin like protease of P.gingivalis .

71. Anti-calculus agents Acids Alkalis Chelating agents Enzymes Urea Antimicrobials Metals Bisphosphonates Victamine C Pyrophosphates Polymers & copolymers

72. Acids One of the earliest techniques to dissolve calculus was to use wooden stick moistened with Aromatic sulfuric acid (Barker 1872). This technique was modified by Niles (1881) who suggested the use of Nitomuriatic acid. Other acids included are: 20% trichloroacetic acid Bifluoride of mercury 10% sulfuric acid The problem with acids is that they are caustic to soft tissues and decalcify tooth structure. Stones (1939) reported that ability of an acid to dissolve tooth structure was greater than its ability to dissolve calculus.

73. Alkalis Badanes (1929) noted the beneficial effect of Natural mineral waters on the removal of calculus because of its alkali content. It dissolves the three principle constituents of salivary calculus; globulin, mucin and calcium oxalate. But this idea did not find support.

74. Chelating agents Chelating agents are used to dissolve crystallized calcium salts and are capable of combining with calcium to form stable compounds. Sodium hexametaphosphate was found to remove supragingival calculus from extracted teeth in 10-15 days (Kerr & Field 1944). Warren et al (1964) found that with sodium hexametaphosphate decalcification of cementum was greater than that of calculus. Because of this finding its use was ceased. EDTA gel ( Sofscale ) has been used as a pre-scale gel to soften the calculus by Jabro et al, 1992 . but its efficacy has not been supported by other studies.

75. Enzymes The mode of action of enzyme preparation is to break down plaque matrix or to affect the binding of calculus to the tooth. The first enzyme to be tested was mucinase (Stewart 1952) and it was found to reduce calculus formation and calculus which did form was softer and more easily removed. Dehydrated pancreas ( Viokase ) was found to reduce calculus formation by 60% (Jensen et al 1959) . Viokase was introduced into chewing gums. Enzymes of fungal origin have been found to be superior to Viokase in reducing calculus formation (40.5% v 14.5%).

76. Urea The idea of using urea as a anti-calculus agent stems from its solvent action on protein. Urea at a concentration of 30% causes maximum reduction of calculus. Acetohydroxamic acid ( AHA ) – irreversible inhibitor of urease has been studied as an anticalculus agent but results are not significant and further it leads to increase in caries.

77. Antimicrobials Penicillin, Cetylpyridinium chloride, Nindamycin, Triclosan and chlorhexidine have been studied as an anti-calculus agent. Out of these penicillin and cetylpyridinium chloride have not been found to decrease calculus levels. Although chlorhexidine is a potent antiplaque agent but it leads to increase in calculus levels ( Loe et al 1976, Lang et al 1982, Grossman et al 1986). Nindamycin has been found to decrease calculus formation but it is not used because of concern for bacterial resistance. Triclosan has been found to assist in plaque control and inhibition of calculus formation although to what extent, its not clear. It is predominantly used in combination with other anti-calculus agents.

78. Metals Metal salts inhibit calculus formation by two mechanisms. Firstly they inhibit plaque formation by causing metabolic changes in bacterias. Secondly they inhibit mineralization. A dentrifice containing zinc chloride and sodium fluoride has been shown to retard calculus formation.

79. Bisphosphonates Bisphosphonates are a group of synthetic pyrophosphate analogue which prevent calculus deposition by inhibiting crystal growth. The bisphosphonates studied for their anti-calculus effect are as follows and all of them have been found to reduce calculus formation. EHDP ( Ethanehydroxydiphosphonate ) Sodium etidronate DPD ( Diphosphono -propane-dicarboxylic acid) AHP ( Azacycloheptane 2,2-diphosphonic acid ) PBTA ( 2-phosphonobutane 1,2,4 tricarboxylate )

80. Victamine C It is a surface active organo-phosphorous compound that has been found to be effective in inhibiting the invitro crystallization of calcium phosphate onto the smears of supragingival calculus. Victamine C has a specific taste that leads to increased saliva flow that leads to reduction in calculus.

81. Pyrophosphates Prevent calcification by interrupting the conversion of amorphous calcium phosphate to hydroxyapatite. The results from clinical studies are not found to be significant so they are not in use.

82. Polymers and copolymers The following agents have been tried: Oligomer of sulfoacrylic acid EDITEMPA BTC/copolymer mixture Gantrez (0.05% solution of methoxyethylene and maleic acid) All of them have been shown to have anti-calculus effect either alone or in combination with other agents such as combination of incorporation of copolymer in a periodontal pyrophosphate / NaF paste.

83. Ellingson JE et al. 1980 , conducted a study to show the effect of stannous and stannic ions on the formation and acido-genicity of dental plaque. 5 dental students were included in the study to study the inhibition of plaque. The pH of the plaque was measured in situ. The stannous ion showed marked inhibiting activity on plaque formation whereas the stannic ion showed only a slight effect. The stannous ion also showed an effect in reducing the acido-genicity of dental plaque whereas the stannic ion showed no such effect. These findings support the concept that the stannous ion reduces the metabolic activity of plaque by oxidation of thiol groups by affinity for these groups.

84. Ogaard B etal. 1980 investigated the plaque-inhibiting effect of a dentifrice containing stannous fluoride/stannous pyrophosphate during treatment with fixed orthodontic appliances. The test toothpaste was compared with sodium monofluorophosphate toothpaste and paste without fluoride and tin. A double-blind cross-over designed study with twenty-one subjects showed statistically significant plaque inhibition after a 3-week test period on subjects showed statistically significant plaque inhibition on teeth with the appliances placed more than 1.5 mm. from the gingival margin

85. Plaque reduction on teeth with the appliances placed close to the gingival margin was not statistically significant. No statistically significant improvement in the gingival condition and no side effects were observed. It is concluded that because of its dual action on plaque and teeth stannous fluoride/stannous pyrophosphate toothpaste may be recommended as supplement to and not substitute for other forms of fluoride supplementation in this category of patients.

86. Tinanoff N et al. 1980 conducted a double-blind, crossover design on 29 young adults to test the effectiveness of 0.1% SnF2 mouthrinse (250 ppmF -) on plaque formation using clinical and microbiological criteria. Participants were assigned to either a placebo or SnF2 rinse which was used twice daily for 5 days. After an interim recovery period of 2 days, the participants used the alternate rinse in a similar manner for another 5 days. Supragingival plaque removed from each subject at the end of the experimental periods was weighed and then microbial enumeration was performed.

87. Results showed that after SnF2 rinses, there were statistically significant reductions (P < 0.01) in plaque wet weight, number of bacteria per milligram plaque (CFU/mg), and total number of bacteria per sample (Total CFU). Visual plaque scores (PS) showed a significant (P < 0.05) but small reduction as a result of SnF2 rinse. No significant difference in gingival inflammation was noted. It is apparent from this study that, besides the well-documented ability of SnF2 to increase the resistance of teeth to demineralization, this agent is capable of reducing plaque formation.

88. CONCLUSION In past 50 years, various plaque agents have been formulated Still chlorhexidine is considered as a gold standard by which other agents are standardized Delmopinol & Chitosan show promising prospects Epidemiologic data suggest that compliance to the regular mechanical oral hygiene is relatively poor.

89. Consequently, anti-plaque agents should be used to augment mechanical plaque control. Chemical agents for plaque control hold great promise in disease control & prevention and potentially delay plaque accumulation on teeth. Herbal mouth rinses, quaternary ammonium compounds, phenols, antibiotics, delmopinol and several other agents have shown significant anti-plaque activity. The adjunctive use of essential oil mouth rinses and triclosan dentrifices were found to be effective in reducing plaque and gingivitis

90. REFERENCES Carranza’s clinical periodontology 10 th edition Jan Lindhe Clinical periodontology & Implant dentistry 5 th edition Renato FM, Lorena B, Natalia SJ, Antonio CP, Marcos AC, Magali M, Man CC. A non-staining and tasteless hydrophobic salt of chlorhexidine. Journal of pharmaceutical sciences. 2011 , Aug; 100(8):3130-38. Addy. M. Clinical indications for use of chemical plaque control agents. Periodontology 2000, Vol. 15, 1997, 52- 54