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The Effect of an Experimental Chewable Antiplaque Preparation Containing Chlorhexidine on Plaque and Gingival Index Scores T.T. Nuuja, H.T. Murtomaa, J.H. Meurman and T.J. Pesonen J DENT RES 1992 71: 1156 DOI: 10.1177/00220345920710050501 The online version of this article can be found at: http://jdr.sagepub.com/content/71/5/1156

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The Effect of an Experimental Chewable Antiplaque Preparation Containing Chlorhexidine on Plaque and Gingival Index Scores T.T. NUUJA, H.T. MURTOMAA1, J.H. MEURMAN2,4, and T.J. PESONEN3 The Military Academy of Finland, Helsinki; 'Department of Dental Public Health and 2Department of Cariology, University of Helsinki, Mannerheimintie 172, SF-00300 Helsinki, Finland; and 3Military Pharmacy, Helsinki This clinical cross-over trial investigated the effects of a chewable preparation containing chorhexidine-fluoride-xylitol, xylitol control tablets, or chlorhexidine mouthwash, twice daily, on plaque and gingival index scores of subjects refraining from mechanical cleaning of their teeth. Both preparations containing chlorhexidine were found to be efficient antiplaque agents when compared with the control. There was no statistically significant difference between the tablet preparation and conventional chlorhexidine rinsings with respect to the recorded parameters. Thus, an efficient antiplaque preparation can be made in tablet form, which may have advantages in instances where use of mouthwash solutions is impracticable. J Dent Res 71(5):1156-1158, May, 1992

Introduction. Chlorhexidine is the drug of choice for the chemotherapy of dental plaque infections (Scheie, 1989). It has been administered mainly in mouthwash solutions or dental gels, but also in chewing gums (Ainamo et al., 1990). A tablet preparation has been suggested where chlorhexidine was combined with two other well-known dental preventive agents, viz., fluoride and xylitol (Nuuja et al., 1992a). The combination of chlorhexidine and fluoride was originally suggested by Luoma (1972), and its clinical efficacy in the prevention of caries and gingivitis has been verified (Emilson et al. , 1976; Luoma et al., 1978; Dolles and Gjermo, 1980; Katz, 1982; Spets-Happonen et al., 1985). These chemicals also appear to act synergistically when tested in vitro against mutans streptococci (Meurman, 1988). Xylitol is a noncariogenic sweetener which also acts synergistically against plaque bacteria when used together with fluoride (Scheinin and Mdkinen, 1975; Scheie et al., 1988; Arends et al., 1990). This study sought to compare the antiplaque effects of the tablet chlorhexidine-fluoride-xylitol combination, control tablets containing xylitol, and conventional chlorhexidine rinsings.

preparations, 20 Wg benzyldiethylammonium benzoate (Bitrex, Atomergic Chemicals Co., NY) was added to the control. This

substance is a commonly used additive which has a bitter taste (Sudgen et al., 1978). Pre-study screening and prophylaxis. -Before the experimental periods, all the subjects were examined by a dentist. The hygiene students gave professional prophylaxes to each other before the onset of the study and two weeks after the initial examination, in order to standardize their periodontal status as far as possible. Clinical record and dental plaque index scores. -Recordings of Plaque Index (Silness and Lbe, 1964) and Gingival Bleeding Index (Ainamo and Bay, 1975) were made by one dentist only (T.N). The total plaque area was determined by the staining of the teeth with basic fuchsin. Two photographs were then taken of the buccal

surface of the left upper first premolar. The photographs were used for calculation of the percent of tooth surface covered by plaque by means of computerized planimetry (Houston Instruments HIPAD DT-114 digitizing plate connected to an IBM PCXT computer). A special plastic instrument was used for collection of dental plaque from all teeth on the right side. The plaque was placed into pre-weighed micro-centrifuge test tubes (Etemadzadeh et al., 1989), weighed immediately in a Mettler precision balance, and the wet weight recorded. At the follow-up examinations, the investigator recorded staining of the subjects' teeth by using the following coding: 0 = no staining, 1 = mild staining, and 2 = severe

staining. Questionnaire.-At all the follow-up examinations, the subjects received a questionnaire where their own opinions about the cleaning effect and taste of the assigned preparation and staining of teeth were requested. A five-grade scale was used in the inquiries, and space was also provided for written comments. Experimental design and study protocol.-The investigator was blind with regard to the preparation used in each study period. The subjects were placed at random into three groups: Group I started with the control tablets, group II with the Hibitane Dental solution, and group III with the XYLIHEX tablets. ThereMaterials and methods. after, each group crossed over to another preparation until all Subjects.-Fifteen healthy dental hygiene students, mean age 32.0 subjects had used all three preparations. ± 6.8 (S.D.), were included in

this cross-over study. Three subjects were regular smokers. The ethical guidelines given in the Declaration ofHelsinki (1975) in its revised form were followed throughout. The study plan had been accepted by the Ethical Committees of the institutes participating. Test preparations.-The following preparations were studied: (1) an experimental chewable tablet ("XYLIHEX") containing chlorhexidine diacetate (10 mg), sodium fluoride (5 mg), and xylitol (609 mg); (2) chlorhexidine digluconate solution (Hibitane Dental, ICI, Great Britain) containing 2 mgper mL chlorhexidine; and (3) a control chewable tablet containing only xylitol. To mimic the bitter taste of chlorhexidine, apparent in Hibitane Dental and XYLIHEX

The experimental periods lasted one week each, with threeweek periods between. The subjects refrained from all mechanical cleaning of their teeth (such as brushing and flossing) during the experimental weeks. Instead, they used the assigned experimental preparation twice daily. The chewable preparations were chewed, and the resulting oral fluid was kept in the mouth for 60 s until expectorated. The Hibitane Dental solution was also kept in the mouth for 60 s. The subjects kept a diary of their chewing/ rinsing protocol. Space was provided for written comments on the compatibility of the preparations. Before and after each experimental week, the subjects thoroughly cleaned each other's teeth with a professional prophylaxis. Statistical analyses.-The Statistical Analysis System packReceived for publication June 24, 1991 age (SAS Institute Inc., NC) was used for calculation of descriptive Accepted for publication October 29, 1991 statistics. Data from the experimental weeks were combined and 4To whom correspondence and reprint requests should be addressed This study was financially supported by grants from the Finnish Army analyzed with respect to the three preparations. The analysis of Headquarters and by the Finnish Dental Society. The Hibitane Dental variance was used, and differences between means of parametric solution used in this study was donated by ICI-Pharma, Helsinki, Finland. variables of the groups were tested against each other by use of 1156

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Vol. 71 No. 5

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CHEWABLE ANTIPLAQUE PREPARATION

the t test (Freund et al., 1986). The staining of the teeth was analyzed by Categorical Data Modeling (Grizzle et al., 1969). Results of the questionnaire were analyzed by use of paired data on non-parametric ANOVA and the Chi-square test.

tically significant differences between the XYLIHEX tablets and the Hibitane Dental solution in their effects on these parameters, while they both significantly reduced these parameters compared with the control (p < 0.001).

Results.

Discussion.

The results were based on the data from the 15 subjects, all of whom completed the study. Baseline data.-At baseline, the following mean index scores were recorded: P1I 0.01 ± 0.02 (S.D), GBI 1.1 ± 1.8. The mean percent of the area of the left upper first premolar covered by plaque was 2.6 ± 2.3 %, and mean plaque wet weight was 0.1 ± 0.1 mg. Staining of teeth.-The Table presents the results of tooth staining. There was no statistically significant difference in staining caused by the Hibitane Dental solution and the XYLIHEX tablets, but both preparations caused significantly more staining than the control tablets (p < 0.05). Results on staining from the questionnaire were in accordance with the investigator's observations. Questionnaire.-The subjects considered that the Hibitane Dental solution and the XYLIHEX tablets had cleaning effects on the teeth, while the control tablets did not appear to have an inhibitory effect on plaque (p < 0.001). In this respect, there was no statistical difference between the effects of XYLIHEX and Hibitane Dental. The tastes of XYLIHEX and Hibitane Dental were equally disliked, and both preparations were considered worse in taste than the control tablets. Both XYLIHEX and Hibitane Dental caused temporary numbness of the tongue reported by nine and eight subjects, respectively. One subject reported numbness also after using the control. Plaque and gingival index scores. -The mean values of plaque wet-weights, P1I and GBI scores, and percentage areas of plaque covering the left upper first premolar before and after the experimental weeks are presented in the Table. There were no statis-

The XYLIHEX tablets appeared to be as effective antiplaque agents as conventional chlorhexidine rinses. The subjects were all healthy young women with no impairment in salivary secretion rate. It could thus be anticipated that the chewable preparation would quickly mix with saliva in the mouth to form a mouthwash. The fact that the bitter taste of chlorhexidine stimulates salivary secretion was the reason we also included the bitter-tasting ingredient (Bitrex) in the control tablets. Since only 20 ,ug of Bitrex was added, there was no reason to believe that it would interfere with plaque accumulation. This reasoning was also confirmed by the present results. Loe and Schi6tt (1970) have shown that chlorhexidine may be retained in the mouth for up to 12 h after rinsing. Salivary clearance, on the other hand, depends on (among other things) the flow rate which is stimulated by masticatory movements (Mayhall, 1975; Dawes, 1987). All our subjects had a full dentition, and thus it remains to be investigated whether the tablet preparation would suit patients with impaired salivary flow. This study aimed to investigate only the antiplaque efficiency of XYLIHEX compared with Hibitane Dental and the control. It is known that, in an experiment of short duration, the selected combination of chlorhexidine, fluoride, and xylitol is no more effective than chlorhexidine alone (Nuuja et al., 1992a,b). Thus, the potential anti-caries activity of the combination tablet must be assessed in future long-term trials. Xylitol alone has been shown to have a favorable effect on the incidence and progression of caries (Kandelman et al., 1988; Isokangas et al., 1988; Kandelman and Gagnon, 1990). In high concentrations, xylitol may also affect bacterial membranes in mutans streptococci (Tuompo et al., 1983). Thus, the selection of

TABLE MEAN (S.D.) PLAQUE WET WEIGHT (mg), PLAQUE INDEX, GINGIVAL BLEEDING INDEX, PLAQUE AREA PERCENT, AND STAINING OF THE TEETH (NO. OF PERSONS) BEFORE AND AFTER SEVEN-DAY EXPERIMENTAL PERIODS

Control Group

Day 0 Day 7

0.05 4.4

(0.08) (2.2)

XYLIHEX Group

Hibitane Dental Group Plaque Wet Weight 0.04 (0.09)

0.06

(0.04)

0.04

(0.09) (0.06)

(0.02) (0.01)

0.01 0.03

(0.03) (0.06)

1.0 0.7

(1.8) (1.5)

2.4 1.3

(1.9) (1.5)

0.02

Plaque Index Day 0 Day 7

0.01

Day 0 Day 7

0.7

Day 0 Day 7

1.08

16.1 3.3

50.3

14 No staining 1 Mild staining Severe staining -

(0.02) (0.27) (1.3) (16.3) (2.6) (12.3)

0.01 0.003

Gingival Bleeding Index 0.4 (1.4) 1.0 (1.5) Plaque Area Percent 2.1 (2.0) 1.2 (1.3) Staining of the Teeth 8 6 1

8 7

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J Dent Res May 1992

NUUJA et al.

xylitol in the control tablet can be criticized. However, we wanted to make the control as close to XYLIHEX as possible, in both consistency and taste. Also, there was no reason to expect that xylitol would have any effect on the plaque weight or plaque and gingival index scores. A chewable antiplaque agent would be valuable in many instances when the use of bottled mouthwash solutions is impracticable. In extreme conditions-such as during combat exercises and maneuvers in the army, or on long-haul flights, for examplechemical plaque control would be desirable. Thus, convenient and efficient antiplaque agents such as chewing gums (Ainamo and Etemadzadeh, 1987) or tablets, as in the present study, may offer interesting perspectives for the future control of dental plaque.

Acknowledgments. We thank J. Pohjola, Head of Military Pharmacy, who placed the facilities at our disposal, and J. Metteri, Finnish Army Headquarters, for performing the statistical analyses. L. Lappi, RDN, is thanked for help at the Helsinki IV School and Institute for Health Personnel Education. REFERENCES Ainamo J, Bay I (1975). Problems and proposals for recording gingivitis and plaque. Int Dent J 25:229-235. Ainamo J, Etemadzadeh H (1987). Prevention of plaque growth with chewing gum containing chlorhexidine acetate. J Clin Periodontol 14:524-527.

AinamoJNieminenA,WesterlundU(1990). Optimal dosageofchlorhexidine acetate in chewing gum. J Clin Periodontol 17:729-733. Arends J, Smits M, Ruben JL, Christoffersen J (1990). Combined effect of xylitol and fluoride on enamel demineralisation in vitro. Caries Res 24:256-257. Dawes C (1987). Physiological factors affecting salivary flow rate, oral sugar clearance, and the sensation of dry mouth in man. JDent Res 66 (Spec Iss):648-653. Declaration of Helsinki (1975). Guidelines for doctors using humans in biomedical research. Approved by the 18th World Medical Association Assembly in Helsinki, Finland, 1964, and revised at the 29th World Medical Association Assembly in Tokyo, Japan, 1975. Dolles OK, Gjermo P (1980). Caries increment and gingival status during 2 years' use of chlorhexidine and fluoride-containing dentifrices. Scand J Dent Res 88:22-27. Emilson CG, Krasse B, Westergren G (1976). Effect of a fluoride containing chlorhexidine gel on bacteria in human dental plaque. ScandJDentRes 84:55-62. Etemadzadeh H, Meurman JH, Murtomaa H, Torkko H, Lappi L, Roos M (1989). Effect on plaque growth and salivary micro-organisms ofaminestannous fluoride and chlorhexidine-containing mouthrinses. J Clin Periodontol 16:175-178. Freund RF, Littell RC, Spector PC (1986). SAS system for linear models. Cary (NC): SAS Institute, Inc. Grizzle JE, Starmer CF, Koch GO (1969). Analysis of categorical data by linear models. Biometrics 25:489-504.

Isokangas P. Alanen P. Tiekso J. M kinen KK (1988). Xylitol chewing-gum in caries prevention: a field study in children. JAm DentAssoc 117:315320. Kandelman D, Bar A, Hefti A (1988). Collaborative WHO xylitol field study in French Polynesia. Baseline prevalence and 32 month caries increment. Caries Res 22:52-66. Kandelman D, Gagnon G (1990). A 24-month clinical study ofthe incidence and progression of dental caries in relation to consumption of chewing gum containing xylitol in school preventive programs. J Dent Res 69:1771-1775. Katz S (1982). The use of chlorhexidine and fluoride for the prevention of radiation caries. JAm Dent Assoc 104:164- 170. Loe H, Schiott R (1970). The effect of mouthrinses and topical application of chlorhexidine on the development ofdental plaque and gingivitis in man. J Periodont Res 5:79-83. Luoma H (1972). The effects of chlorhexidine and fluoride combination on the potassium, sodium and phosphorus content and acid production of cariogenic streptococci. Arch Oral Biol 17:1431-1437. Luoma H, Murtomaa H, Nuuja T, Nyman A, Nummikoski P, Ainamo J, Luoma A-R (1978). A simultaneous reduction of caries and gingivitis in a group of school children receiving chlorhexidine-fluoride applications. Caries Res 12:290-298. Mayhall CW (1975). The physiological roles of saliva. AL J Med Sci 12:4563. Meurman JH (1988). Ultrastructure, growth and adherence of Streptococcus mutans after treatment with chlorhexidine and fluoride. Caries Res 22:283-287. Nuuja T, Meurman JH, Murtomaa H, Kortelainen S, Metteri J (1992a). The effect of combination of chlorhexidine diacetate, sodium fluoride and xylitol on plaque wet weight and periodontal index scores in military academy cadets refraining from mechanical tooth cleaning for 7-day experimental periods. J Clin Periodontol 19:73-76. Nuuja T, Meurman JH, Torkko H, Murtomaa H (1992b). Effect of an experimental antiplaque preparation on salivary microbial counts in military academy cadets refraining from mechanical cleaning of the teeth. Milit Med (in press). Scheie AAa (1989). Modes of action of currently known chemical antiplaque agents other than chlorhexidine. JDent Res 68:1909-1916. Scheie AAa, Assev S, Rolla G (1988). Combined effect of xylitol, NaF and ZnCl2 on growth and metabolism of Streptococcus sobrinus OMZ 176. Acta Pathol Microbiol Immunol Scand 96:761-767. Scheinin A, M kinen KK (1975). Turku sugar studies I-XXI. Acta Odontol Scand 33 (Suppl 70). Silness J, Loe H (1964). Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand 22:121-135. Spets-Happonen S, Markkanen H, Pollanen L, Kauppinen T, Luoma H (1985). Salivary Streptococcus mutans count and gingivitis in children after rinsing with a chlorhexidine-fluoride solution with and without strontium. Scand J Dent Res 93:329-335. Sudgen K, Mayne TG, Loscombe CR (1978). Determination of denaturants in alcoholic toilet preparations. Analyst 103:653-656. Tuompo H, Meurman JH, Lounatmaa K, Linkola J (1983). Effect of xylitol and othercarbon sources on the cell wall of Streptococcus mutans. Scand JDent Res 91:17-25.

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The effect of an experimental chewable antiplaque preparation containing chlorhexidine on plaque and gingival index scores.

This clinical cross-over trial investigated the effects of a chewable preparation containing chorhexidine-fluoride-xylitol, xylitol control tablets, o...
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