Anti-plaque agents. Rationale and prospects for prevention of gingivitis and periodontal disease

R J. G, van der Ouderaa

Unilever Dental Research, Port Sunlight Laboratory, Bebington, Merseyside L63 3JW UK

Van der Ouderaa EJG: Anti-plaque agents. Rationale and prospects for prevention of gingivitis and periodontal disease. J Clin Periodontol 1991; 18: 447-454. Abstract. Oral health surveys have shown that even in countries with established patterns of oral hygiene habits, most individuals have relatively poor gingival health. This is due to a low interest in complying with oral health procedures. A number of factors are apparent when investigating compliance to oral hygiene habits, viz only approximately 50% of the population brushes twice a day or more, brushing time is probably much too short and use of dental floss is not very prevalent. Studies of the effect of motivation on oral hygiene suggest that improvements can be achieved, but these are not maintained unless motivation is continuously reinforced. This suggests that topically applied anti-plaque agents should be used to augment mechanical plaque control. A number of product forms are available to delivery anti-plaque agents i.e., mouthrinses, dentifrices, aqueous gels, and additionally floss , chewing gum and lozenges. Any product form should provide a physically, chemically and microbiologically stable environment for the agent concerned. It should facilitate optimal bioavailability of the agents at the site of action and encourage patient compliance. Antiplaque agents for topical administration should have the following properties: high intrinsic efficacy against a broad spectrum of oral organisms, toxicological and ecological safety, oral substantivity, no adverse reactions and good chemical stability. A number of classes of anti-plaque agents have been identified such as positively charged organic molecules, metal salts, phenols, enzymes, peroxides, sugar substitues, fiuorides and surface modifying agents. In order to achieve optimal bioavailability, the agent to be dosed should be compatible with the product form used. The 2 major product forms are rinses and dentifrices. With respect to rinses as the product form, the formulation excipients are generally compatible with positively charged organic agents, phenolic agents and some metal salts. In the case of dentifrice formulations, interactions of the agent with the product excipients limit compatibility to some metal salts and non-charged phenolic agents, triclosan being a well researched example. The combination of metal salts, in particular zinc, and the phenolic agent triclosan has been shown to represent a further powerful route to enhance systems for daily plaque control.

In recent years, spectacular progress has been made in the reduction of dental caries in many Western industrialised countries (R0lla & Ogaard 1987, Brunelle & Carlos 1990, Kalsbeek & Verrips i990). The recent data with respect to the prevalence of periodontal diseases are not as reassuring. The aim of this raper is to review periodontal status at : le population level and additionally, to ( iscuss habits and patient compliance 1 ita in order to consider measures for j riodontal prevention for incorpor; ion into existing oral health pro( dures. Potential chemical agents for

supragingival plaque control and the principles of their delivery are discussed. Oral Health: Population Data

Several reviews of extensive data bases have recently been published. 2 compilations of CPITN data contained in the WHO Global Oral Data bank (Pilot et al. 1986, Pilot et al. 1987) show that signs of periodontal disease are extremely prevalent. Gingival bleeding, calculus and shallow pocketing are the most frequently observed conditions in the adult group (35-44 years of age)

;

Key words: plaque; gingivitis; periodontitis; drug delivery; oral substantivity; anti-plaque agents. Accepted for publication 18 September 1990

and calculus with and without gingival bleeding-on-probing are the most prevalent conditions in the adolescent group (15-19 years of age). Cutress (1986), in a similar review of global data of young people (11-19 years of age), observed a high degree of plaque associated marginal gingivitis in all populations assessed. Healthy individuals were in the minority being less than 10% of the total examined. Brown et al. (1989), reporting on an extensive, in-depth Dental Health survey, concludes that only 15% of the US population is free of signs of periodontal disease. Whilst,

448

Van der Qvderaa

on average, 50% of all teeth assessed were found to b« free of periodontal disease, approximately 40% of all teeth showed evidence of gingivitis, 8% had periodontjtis and 2% had advanced periodontitis (defined as having at least one pocket greater than 6 mm). Ainamo (1989) reports 25-50% of dentate European 64-year-olds as having advanced periodontal disease by the same criterion. These trends identified are probably valid globally because the studies cited are large and the data originate from widely different countries, which means that variations in ethnic and age related disease propensity as well as patient oral hygiene and dietary habits are probably well accounted for. The very considerable reduction in the prevalence of caries is likely to result in a redxiced rate of tooth loss from caries and, concommitantly, reduced edentulousness. Recent data for the United Kingdom (Government Statisticai Service, 1990} show a reduction of edentulousness in adults from 13% in 1978 to 4% in 1988 for the 34 to 44 age group and from 32% in 1978 to 17% in 1988 for the 45 lo 54 age group. In the group below 33 years of age, edentulousness is now less than 1% (1988 data). The above trends and the general longer life expectancy suggest that periodontal disease may become more prominent as a public health problem (Williams 1990) if preventative strategies are not initiated. Disease Mechanism Considerations From the pioneering experimental gingivitis experiments of Loe et al. (1965) it can be deduced that supra-gingival plaque is the main aetiological factor for gingivitis, Further evidence is provided from subsequent experiments using the same experimental protocol, which show that agents that substantially inhibit the accumulation of supra-gingival plaque can prevent the development of gingivitis (e.g., Siegrist et ai. 1986). Until recently, it was assumed that all gingivitis would ultimately lead to periodontal destruction, however, it has now been realised that not all gingivitis progresses to periodontitis (Listgarten 1986). Some forms of periodontitis can occur almost independently of gingivitis, e.g., in patients with a genetic disposition for juvenile periodontitis (Page et al. 1987). Nevertheless, it is generally assumed that the presence of gingivitis

resulting from the inflammatory challenges of supragingivai plaque is a strong predisposing factor for disease progression, gingivitis likely provides the ecological niche for changes in the ecology of the plaque, which may become more pathogenic and consequently facilitates the type of sub-gingival colonization which could lead to periodontal destruction (Schroeder 1986, Christersson et al. 1989). Can sub-gingival colonization be prevented? There is strong evidence that excellent supra-gingival plaque control reduces and may prevent sub-gingival colonization (Waerhaug 1979, 1981). Furthermore proper supra-gingival plaque control can prevent breakdown of healthy sites and even arrest lesions (Abdellatif & Burt 1987, Attstrom 1988). Longitudinal studies have shown that, following prophylaxis, oral hygiene instruction and motivation, excellent individual plaque control can result in cessation of progression of periodontal disease in the populations studied (Lindhe & Nyman 1975, Axelsson & Lindhe 1978). Consequently, the principle of prevention of periodontal disease by means of supra-gingival plaque control is well established. Unfortunately, it must be concluded from the high incidence of gingival inflammation observed in the field studies discussed above, that the average individual does not exercise the degree of plaque control required to maintain a healthy peridontium and is, hence, at risk of periodontal disease. The general population is apparently insufficiently motivated to prevent oral disease (Wilson 1987). Behaviour, Habits and Compliance It is appropriate to analyse attitudes and behaviour in relation to achieving good oral hygiene, since its attainment can play such an important role in maintaining a functional periodontium. There are a great number of general factors influencing the dental behaviour of populations, such as culture, diet, overall level of education, domestic circumstances, disposable income, availability of dental manpower (WHO Scientific Group 1978), and also important are communication channels for advertising of dental products and services and the nature of health insurance systems. Superimposed on these are individual factors which include sub-sets of the above as well as beliefs

and attitudes to personal care, frequency of dental visits, age and smoking habits (Glavind 1986). Additionally, there are a number of factors directly related to oral health which include oral physiology, frequency and effectiveness of brushing, degree of use of interdental aids, manual dexterity, toothbrush quality and state of wear and the quality of dental restorations. An analysis of some of the latter behavioural factors may help in understanding the population's relative poor state of periodontal health. The first issue on which there are some limited data available is 'reported' brushing frequency, examples of which are shown in Table 1. Around 50% of the participants interviewed in most studies claim to brush twice a day; a further small portion more than 2 x day. Even this may be an overestimate since those results were obtained from questionaires and similar reports by individuals rather than by objective measurement. Self reporting is generally assumed to over-estimate the actual situation in most market research situations. A second issue related to personal oral hygiene is brushing time. An oral habits study in Italy was carried out in which brushing time was assessed by direct observation in the subject's home (Cox & Cowell 1983 unpublished data). The average recorded brushing time was 37 s (Fig. 1); with a quarter of the people studied brushing for less than 20 s. Use of interdental aids such as fiossing has been reviewed (Pader 1988). It was found in a study of relatively affiuent American families, that daily flossing was practised by 20% of wives, 11 % of husbands and 6% of children (Chen & Rubinson 1982). Up to 50% of wives flossed at least once a week. These data may well be an overestimate compared to other societies. Whilst the above data on brushing frequency, duration of brushing and frequency of fiossing may not be comprehensive, its pattern is consistent with the oral condition as indicated by the population data cited above. It is tempting to speculate that the few individuals who were observed as periodontalh healthy in the population studies, wen those individuals who brush twice a da; or more, for sufficient lengths of time A further parameter mentionei above as a potential factor is toothbrusl quality and wear. Although difference in clinical cleaning efficacy between bru

Anti-plaque agents: rationale and prospects

449

Table 1. Brushing frequency Country Age group Author Year* Panel size Frequency of brushing per day 1 2 >2 Changing Other answers Never

US

UK

UK

Finland

UK

Italy

9-13

13

14

15-19

adults over 16

adults

Berenie et al.

Burchell et al.

1973 384

1990 3005

Macgregor & Balding 1987 3727

Nyyssonen & Hankala 1984 1924

Todd & Walker 1978** 2912

Cox & Cowell a) 1984**

%

%

%

%

%

%

13 37 37 13

19 39 47 5

i -,

1

54 10

176

16

27

10

19

50 14

43 47

"-•

54 7 2

* Year of publication. ** Year of Data Collection, a) Cox, D. L. and Cowell, C. R. unpublished results

shes do exist (Rueger et al. 1986), most would result in good periodontal health. multi-tufted brushes have the potential Nevertheless, one should not lose sight to be effective and safe cleaning aids of the fact that health, in principle, can (Pader 1988). A major practical issue be achieved by relatively simple means. with respect to effectiveness of brushes In recent unsupervised gingival health could well be their very low replacement studies, the first phase consisted of a 4rate. In the majority of countries the week period following dental prophyper capita sales are not higher than one laxis, brushing instruction and motivabrush per person per 2 years. In some tion and twice daily application of a developed countries the average is standard fluoride toothpaste using a somewhat higher, i.e., 1-1.5 brushes per new toothbrush (Svatun et al. 1987, person per year. This is still a low re- Svatun et al. 1989 a, b, Svatun et al. 1990, Stephen et al. 1990). At the end placement rate if one takes brush wear and potential for microbial contami- of this period good gingival health (as nation of the brush into account (Wat- defined by 70% of the People generally use brushes which are participants. The data from one of these well worn and which could be fairly studies are shown in Fig. 2. The results confirm the earlier mentioned obsercontaminated. vations of Lindhe & Nyman (1975) and The above observations indicate poor patient propensity towards the proper Axelsson & Lindhe (1978) in that low attention to oral hygiene habits which bleeding-on-probing scores can be population (%)

0-20

21-40

41-eO

60-80

81-100 101-120 121-140

duration of bru8hing (sees) g. L Time of toothbrushing (sees) in an Italian urban population («= 176) as obtained by -house observation (Cox & Cowell, 1983 unpublished results).

achieved after prophylaxis, instruction and motivation. However as shown in Fig. 2, these potentially healthy individuals, notwithstanding the fact that they were motivated by participation in a clinical trial, underwent a considerable deterioration in their gingival bleedingon-probing scores during the next period of 6 months. Given these clinical trial results, taking into account the behavioural considerations mentioned above and the role of supra-gingival plaque in the aetiology of gingivitis and, perhaps of periodontal disease, there is a clear rationale for anti-plaque agents, the function of which should be to augment mechanical plaque control (Kornman 1986, Mandel 1986). Delivery Systems for Control of Periodontal Health

Different treatment needs will require different strategies with respect to delivery of appropriate agents to relevant oral sites (Kornman 1986). For instance, advanced periodontal lesions at risk of further breakdown may require local or systemic treatment with antibiotics, whilst supplementing mediocre supra-gingival plaque control may require a much less powerful anti-plaque agent. Furthermore different delivery systems should be employed to facilitate delivery to the site concerned. The main delivery routes for administration of anti-plaque agents for supra- and subgingival plaque control either by self, or professional application, are shown in Table 2 (for review, see Van der Oud-

450

Van der Ouderaa tail in the remainder of this paper. In the light of this, one important class of anti-plaque agents used to arrest advanced lesions, the antibiotics, will not be considered. Apart from the fact that their therapeutic value is questioned (Van Palenstein Helderman 1986, Lang 1988), these drugs are not available for "over-the counter" (OTC) administration.

(%> Silas Blaading on Probing

P/t/M 26

20

16

10

Delivery System Requirements

0

1

4

7

.

Months

Fig. 2. Gingival condition after prophylaxis' oral hygiene instruction and patient motivation. Volunteers (« = 72) were assessed for gingival bleeding-on-probing and subsequently scaled and motivated (P/I/M) at the start of the study. They were asked to brush twice daily with a standard fluoride toothpaste and further bleeding-on-probing assessments were carried out at 1, 4 and 7 months (Stephen et al. 1990).

eraa & Cummins (1989)). Agents designed to affect supra-gingival plaque can be delivered, in principle, by topical delivery vehicles such as dentifrice, rinse, chewing gum; assuming proper compatibility ofthe agent and the product vehicle during application. Agents aimed to affect sub-gingival plaque in established lesions should be applied systematically or locally in the pocket using sub-gingival irrigators or sustained release fiber systems (Van der Ouderaa & Cummins 1989, Goodson 1989). Supra-gingival plaque control and the prevention of early gum disease using self prevention systems such as rinse and/or dentifrices as the delivery vehicles will be looked at in greater de-

As for any system for drug delivery, product forms designed to deliver agents to control supra-gingival plaque should be formulated to comply to a number of basic principles. (i) The product should provide a physically, chemically and microbiologically stable environment for the agent to be dosed over the projected shelf life of the product. (ii) The formulation should be designed to facilitate optimal bioavailability of the agents on release at the site of action in the oral cavity during use. (iii) The product form should encourage patient compliance; mouthrinses and, in particular, dentifrices are already widely used. This is probably because their cosmetic properties enhance perceived mouth freshness and hence social acceptability. To maintain compliance, product properties such as flavour, stain removal and mouthfeel should not be compromised by the inclusion of the anti-plaque agents. Consequently, the basic components incorporated in a dentifrice to produce those properties, in particular the mild abrasive agents, foaming agents and flavours, should be compatible with the anti-plaque system and vice versa. There is less of a compatibility problem between agents and excipients in other, simpler product forms such as rinses

Table 2. Main routes of administration of anti-plaque agents Supra-gingival delivery

Local mouthrinses dentifrices gels irrigators floss cheving gum lozenges

Mode of application self prof.

1/ j/

1/

V] / . 1/ 1/

Sub-gingival delivery

Local irrigators hollow fibre monolytic fibre acrylic strip

Mode of application self prof.

1/

1/ 1/ 1/

V

Systemic capsules (tablets)

Mode of application self prof.

1/

and non-foaming, non-abrasive aqueous gels. In considering anti-plaque agents for self-prevention, agent selection should take into account the constraints placed by the additional functions of the vehicle. (iv) The anti-plaque system should offer a favourable cost-benefit ratio. (v) Use of the system should not result in adverse reactions such as staining of teeth and tongue, impaired taste sensation, oral irritation, mucosal desquamation or pathogenic changes in the mouth flora. (vi) A formulation developed for unsupervised self administration should be in accordance with the requirements of legislative bodies and professional organisations such as the guidelines for acceptance of products for control of supra-gingival plaque and gingivitis (ADA Council of Dental Therapeutics 1986, Ranney 1989). Delivery Considerations: The Agent

A considerable number of factors influence the degree of anti-plaque efficacy obtained in vivo. Some of these are properties of the agent per se; others result from the need to dose the agent via a delivery vehicle. Anti-plaque agents for topical application need to have 6 properties. (i) Intrinsic anti-microbial efficacy against oral organisms (Goodson 1989); the lack of specificity of bacterial species involved in the aetiology of gingivitis (Ranney 1986) suggest that broad spectrum agents should be used. (ii) Substantivity, i.e., the agent should be retained at the site of action after application; Goodson 1989, Van der Ouderaa & Cummins 1989). (iii) Chemical stability during storage. (iv) Absence of adverse reactions such as staining or mucosal interactions. (v) Toxicological safety. (vi) Ecological safety, i.e., use of the agent should not result in development of bacterial resistance or over-growth by opportunistic organisms (Ranney 1989). Of these 6 properties the first three are relevant with respect to efficacy ir vivo. The remaining three are inviolablt safety considerations which determini whether the agent can be used. Current insights in the mechanism o action of a number of agents used ii vivo suggest that, apart from broac spectrum high intrinsic anti-microbia

Anti-plaque agents: rationale and prospects

451

ammonium salts cetylpyridinium chlor- has been observed using a dentifrice as ide and benzalkonium chloride, pyrim- a product form. Use of metal salts in idine derivatives such as hexidine; bisgu- aqueous rinse formulations may result anides such as chlorhexidine, alexidine, in stability problems as some salts, in octenidine and also the plant alkaloid particular of stannous, are prone to presanguinarine. Most of these agents have cipitation to biologically inactive forms good intrinsic anti-microbial activities (Cummins & Watson 1989). This probagainst oral species (Goodson 1989). lem is less in dentifrices because their Their chemical properties render them liquid phase is rich in sorbitol or glycerbioavailable from alcohohc rinses, ol which reduces the water activity. Adchewing gums, lozenges and aqueous ditionally the active state of the metal gels (Walker 1988, Ainamo & Estemad- can be maintained by a judicious choice zadeth 1987). However, these agents are of complexing agents (Cummins & Watnot compatible with most dentifrice for- son 1989). mulations because of their interactions Oral substantivity of metal ions and with the foaming and abrasive agents their uptake by oral reservoirs has been used (Johanson et al. 1975, Van der Ou- described (Afseth et al. 1983, Saxton et deraa & Cummins 1989, Barkvoll et al. al. 1986, Gilbert & Ingram 1988). 1989). Chlorhexidine, in particular, has exNon-charged phenolic agents cellent efficacy in vivo due to a favourable combination of intrinsic efficacy Some members of this class of antiseptic and oral substantivity and is success- agents are suitable for oral applications, fully incorporated into efficaceous OTC in particular, the active ingredients of formulations (for review, see Gjermo listerine and the agent triclosan. Both (1989)). For other positively charged are broad spectrum anti-plaque agents agents with intrinsic anti-microbial ac- in vivo (Jones et al. 1988, Minah et al. tivity comparable to chlorhexidine, the 1989, Marsh 1990). Because of their chnical effects observed are much weak- chemical nature these agents are very er, either due to low substantivity (e.g., stable and no cosmetic negatives or adcetylpyridinium chloride and other verse reactions have been observed monovalent positively charged agents) (Gjermo & Saxton 1990). or a too strong binding to oral reserRecent data show good oral retention voirs resulting in poor bioavailability of and substantivity for triclosan (Gilthe free drug (e.g., sanguinarine) bert & Williams 1987, Cummins 1990). (Goodson 1989). This agent has a low solubility. ConseThe widespread unsupervised use of quently when to be formulated in a denpositively charged anti-plaque agents as tifrice it must be solubilised in the flavadjuncts to improve daily oral hygiene our oil and surfactant. Under the curis hampered by a number of adverse rent conditions it can be formulated to effects such as staining of the teeth, im- be bioavailable from both rinses or denpaired taste sensation (Pader 1988) and tifrices (Van der Ouderaa & Cummins Agents for Chemical Plaque Control increased formation of supra-gingival 1989). Recently favourable clinical effects have been observed for the combiA number of reviews of properties of calculus (Grossman et al. 1986). nation of triclosan and the metal salt chemotherapeutic agents for the control zinc citrate, both in short-term nonof supra-gingival plaque have been pubiVIetal salts brushing models, such as the 21-day exlished recently (e.g., Genco 1981, Kornman 1986a, b, Mandel & Klein- The anti-bacterial activity of metal salts, perimental gingivitis model (Saxton & berg 1986, Newman 1986, Mandel 1988, such as silver, nickel, mercury, zinc, Van der Ouderaa 1989, Jones et al. 1990, Walker 1988, Scheie 1989). Whilst there stannous and copper was described as Cummins 1991) as well as in unsuperviis no good reason to repeat the infor- early as 1940 (Hanke 1940). The intrin- sed brushing studies of up to 12 months mation presented in these papers, there sic efficacy of metals is lower than for duration (Svatun et al. 1987, Svatun et is merit in considering the properties some of the positively charged organic al. 1989 a, b, Svatun et al. 1990, Stephen of these agents against the background agents, in particular their reported MIC et al. 1990, Gjermo & Saxton 1990). described above. This analysis is then values are fairly high, although this is, used to identify favourable agents, or to some extent, due to experimental Enzymes combinations thereof, for inclusion in conditions in MIC tests artificially re'ral health systems for uncontrolled, ducing their bio-availability (Barry Different types of enzyme systems have 1985, Bird et al. 1985). Nevertheless been designed to achieve an anti-plaque aily use. anti-plaque efficacy in vivo of metal effect. Mutanases have been used sucositively charged organic molecules salts such as stannous fiuoride (Svatun cessfully in animal studies to prevent 1981) and zinc citrate (Jones et al. 1988, plaque build up (Guggenheim 1980); his represents a large class of well nown agents, such as the quaternary Saxton et al. 1986, Saxton et al. 1988) however, few human data are available activity, the agent must have oral substantivity (Rolla et al. 1971, Afseth et al. 1983, Goodson 1989). Oral receptor sites can be plaque, the oral mucosa, the surface of the tongue, and the pellicle surface (Van der Ouderaa & Cummins 1989, Gilbert et al. 1989, Cummins 1991). As a result of binding of the agent to these receptor sites during application and subsequent resorption from these reservoirs into saliva, elevated saliva levels of these agents have been observed for considerable periods after application. However, as a result of its relatively high fiow rate compared to its residual volume in the oral cavity, saliva itself is probably not a reservoir in the true sense. From data of Ainamo et al. (1976), it can be deduced that particulate matter is relatively efficiently cleared from the mouth because of the large hydrodynamie forces exerted by saliva. Substantivity can, therefore, best be achieved when the soluble or solubilised species of the anti-plaque agent bind to the reservoir sites (Cummins & Watson 1989, TanWalker & Gilbert 1989). This binding may occur via electrostatic or Van der Waals forces (Van der Ouderaa & Cummins 1989). Whilst this is a very qualitative description, some in vivo observations can actually be explained according to these principles: Bisguanides, such as chlorhexidine, having two positively charged groups, bind more strongly and are, consequently, more substantive than quaternary ammonium salts such as cetylpyridinium chloride with a single charge (Bonesvoll & Gjermo 1978).

452

Van der Ouderaa

(Kelstmp 1979) atid some adverse reactions due to contaminating protease fractions have been reported. Another system is based on a combination of amyloglycosidase and glucose-oxidase to produce oxidative antimicrobial species in situ in plaque from starch via glucose. An initial pilot study showed an anti-plaque effect (Rotgans & Hoogendoorn 1979) but further clinical data of this system were not encouraging (Groeneveld et al. 1984, Etemadzadeh et al. 1985, Afseth & Rolla 1989). Concern must be expressed about the long-term stability of enzyme molecules in environments with potentially high concentrations of alcohol (rinse) or ionic surfactants (dentifrices) as both these components have the intrinsic ability to denature the enzyme activity: no data are available on this issue, however.

Peroxides

Peroxides have been shown to have antimicrobial efficacy against oral bacteria (Miyasaki et al. 1986). The use of hydrogen peroxide containing mixtures has been proposed by Wennstrom & Lindhe (1979) to prevent plaque and gingivitis. Recently new peroxides, i.e., potassium peroxidiphosphate, have been described (Affilitto et al. 1988), Because of their chemical nature these molecules are unstable by design, i.e., they liberate oxidative oxygen species in situ which may have an anti-plaque effect. The data available do not peraiit a judgement on their usefulness.

Sugar substitutes

Agents such as xylitol and mannitol have been advocated as anti-plaque agents (Scheie 1989), and indeed xylitol has been incorporated in chewing gum formulations to prevent reductions in plaque pH, because of their effect on metabolism of streptococci (Assev et al. 1989). As anti-plaque agents their intrinsic activity is much lower than that of most above mentioned agents. Because of their lack of charge and high aqueous solubiUty their substantivity is probably low although no data are available. Currently no data are available for the effect of incorporation of xylitol in rinses or dentifrices; however the prospects must be considered mediocre.

Piuorides

,

;

,

It has been well-estabhshed that fluoride ion can inhibit carbohydrate utilization of oral organisms by blocking enzymes involved in the glycolytic pathway (Hamilton 1990). Fluoride prophylaxis is abundantly used in oral health products, i.e., fluorides are already present in most dentifrices and some mouthrinses. Fluoride at prophylactic levels probably does not alter the plaque ecosystem (Bowden 1990) and the in vivo data on anti-plaque effects of fluoride are related to stannous fluoride (Svatun 1981, Kornman 1986). The effect of this fluoride salt is due to its stannous content. Surface modifying agents

A recent review of in vivo apphcations of surface alteration agents (Glantz & Attstrom 1986) concluded that these agents were in an early stage of development. Recently new polymers such as sodium polyvinylphosphonic acid (Giertzen et al. 1989) and perfluoroalkyl surfactants (Gaffar et al. 1988) have been described. Whilst initial results may be encouraging, lack of data does not permit an assessment of their potential. Conclusion This paper set out to analyse the average oral condition and the means to improve this within currently established oral hygiene procedures. From the epidemiological and behavioural data it can be concluded that compliance to regular mechanical oral hygiene is relatively poor. Consequently, anti-plaque agents should be used to augment mechanical plaque control. Depending on what product vehicle the patient prefers to use, a number of routes are available for the formulation of efficacious preventive systems for daily use. In the case of rinses and aqueous gels, the product excipients are compatible with positively charged organic agents, phenolic agents and some metal salts. In contrast, in the case of dentifrice formulations the product excipients limit compatibility to some metal salts and non-charged agents, triclosan being a well researched example. There is now good evidence that the combination of metal salts, in particular zinc with triclosan, represents a further powerful agent formulation for daily plaque control.

Acknowledgements

The author would like to thank Dr. D. Cummins and Dr. D. Purdell-Lewis for their comments on the manuscript. References Abdellatif, H. M, & Burt, B, A, (1987) An epidemiological investigation into the relative importance of age and oral hygiene status as determinants of periodontitis. J. Dent. Res. 66, 13-18. Afflitto, J., Gaffar, A. & Moreno, E. C. (1988) Effects of tetrapotassium peroxydiphosphate on plaque/gingivitis in vivo. J. Dent. Res. 67 (Spec. Iss.) 401, abstr, 2309. Afseth, J,, Helgeland, K. & Bonesvoll, P. (1983) Retention of copper and zinc in the oral cavity following rinsing with aqueous solutions of copper and zinc salts. Scand. J. Detn. Res. 91, 42^5, Afseth, J, & R0lla, G. (1989) Clinical experiments with a toothpaste containing amyloglucosidase and glucose oxidase. Caries Res. 17, 472-75, Ainamo, J, (1989) Epidemiology of periodontol disease. In: Textbook of clinical periodontology, 2nd edition, Lindhe J, ed,, pp, 70-91, Munksgaard, Copenhagen. Ainamo, J., Carlson, O., Niemi, M. L, & Vitto, V. J. (1976) Occurrence of polarising particles in residual plaque after brushing the teeth with toothpaste, Swed. Detit. J. 69,49-51, Ainamo, J. & Etemadzadeh, H. (1987) Prevention of plaque growth with chewing gum containing chlorhexidine acetate. /, Clin. Periodontol. 14, 524-527. Assev, S,, Scheie, A. Aa, & R0Ha, G, (1989) Potential of xyhtol, mannitol, and sorbose to inhibit metabolism in streptococcus sobrinus OMZ 176, /, Dent. Res. (Spec, Iss,) 68, 1729-1731. Attstrom, R, (1988) Does supragingival plaque removal prevent further breakdown? In: Guggenheim, B, (ed): Periodontology today, pp 251-259. Basel. Karger, Axelsson, P & Lindhe, J, (1978) Effect of controlled oral procedures on caries and periodontal disease in adults, J. Clin. Periodontol. 5, 133-151, Barkvoll, P, Rolla, G, & Svendsen, A. K, (1989) Chlorhexidine interactions with sodium lauryl sulfate in vivo, /, Dent. Res. (Spec. Iss.) 68, 1722-1723. Barry, A, L, (1985) Procedure for testing antimicrobial agents in agar media: theoretical considerations. In: Lorian, Y (ed,): Antibiotics in laboratory medicine, pp, 1-27. Baltimore Williams and Wilkins. Berenie, J., Ripa, L, W. & Leske, G, (1973 The relationship of frequency of tooth brushing, oral hygiene, gingival health anc caries-experience in school children. J Publ. Health. Dent. 33, 160-171. Bird, N. P, Chambers, J. G., Leech, R. W. & Cummins, D, (1985) A note on the usi of metal species in microbiological testins

Anti-plaque agents: rationale and prospects

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