CA1046417A - Oral preparations for preventing dental caries - Google Patents

Abstract

ABSTRACT
This invention relates to a method for inhibiting the formation of dental plaque and/or dental caries. This invention has identified two compositions, pimento berry oil and terpene-less bay oil, which are effective as antimicrobial agents against cariogenic streptococci and lactobaccilli and which, when topically applied to the teeth, are effective for use in oral preparations as a means to reduce dental plaque and/or dental caries.

Description

The underlying causes of dental caries are multifacet-ed. One aspect is the microbiological one. In order for caries to develop, infection by microorganisms has to occur.
During recent years it has been found that the organ~
isms most often associated with the formation of multi-surface caries are certain salivary streptococci belonging to the strep mutans group. Multi-surface caries is particularly prevalent in children and young adults; the so-called rampant caries belongs to this type. The cariogenic organisms appear to have the special capability of developing a high molecular weight, water-insoluble type of dextran from sucrose. This dextran is believed to be a major constituent of the dental plaque nor-mally associated with dental caries.
Various means have been contemplated for controlling the amount of plaque in the mouth. The use of certain enzymes such as Pancreatin is disclosed is U.S. Patent No. 3,235,460 as effective to inhibit the formation of dental plaque. It has also been proposed to employ direct bactericidal action on the cariogenic microorganisms to assist in the reduction or pre-vention of dental caries. U.S. Patent Nos. 2,921,886 and 3,450,812 respectively disclose alkyl morpholine compounds and nitrogen based compounds having an empirical formula of H61NO14 as antlmicrobials which are effective as anticaries agents.
Coupled with the problem of identifying antimicrobial compounds effective in reducing dental caries is the necessity that the effective substance may be permitted to act on teeth .~' - : .
,: . . . .

in the mouth. Thus, not only must the substance possess the requisite effectiveness, it must also possess certain requisite supplementary characteristics such as satisfactory properties from the viewpoint of oral toxicity, acute chronic toxicity, non-sensitization, etc.
This invention has identified two compositions, pimento berry oil and terpeneIess bay oil, known to have some antimicro-bial properties, as highly effective antimicrobials against selected cariogenic bacteria. These compounds have the apparent ability to either inhibit the growth of or destroy several highly cariogenic species of streptococci and lactobaccili.
The present invention is a method for inhibiting the formation of dental plaque and/or dental caries, which comprises -topically applying to the teeth as an active ingredient an amount of either one or a combination of (a) pimento berry oil and (b) terpeneless bay oil, which is effective in inhibiting the forma-tion of dental plaque and/or dental caries.
According to the present invention, the active ingredients are topically applied to the teeth at levels effec-tive to inhibit the formation of dental plaque and/or caries~
By the phrase topical application to the teeth it is meant that the active ingredient is brought into direct contact with the .-teeth and maintained there for a period of time effective to inhibit the growth of cariogenic bacteria, particularly cario-genic streptococci and cariogenic lactobacilli. The direct contact may be achieved by directly swabbing a concentrated solution of the active ingredient onto the teeth or by holding it in the mouth in a more dilute solution taken directly or derived from a carrier. The active ingredients can be present in suitably effective amounts in preparations such as toothpaste, ;;
tooth powders, mouth washes, or the like, or they may be employed in preparations s~ch as chewing gum or 102enges to provide longer periods of contact with the teeth.
Pimento berry oil is a commercially available composi-tion, used generally as a flavoring material in food products such as chewing gum at levels of up to 0.17%.
Bay oil is also commercially available and is known to be useful as a flavorant in beverages and food products at levels of from about 1.5 to about 15 ppm.
The terpenes can be removed from the bay oil by fractionation techniques known to the art. For example, the terpenes can be removed by fractional distillation.
Such materials as sweeteners, flavoring, coloring or whitening agents, preservatives, alcohols and the like may be readily incorporated into the oral preparations of this invention.
Dentifrice formulations should also contain, as a major propor-tion of the solid ingredients, water-insoluble abrasives or polishing agents such as calcium carbonate, tricalcium phosphate, bentonite, etc.
In the preparation of tooth powders it is usually sufficient to mechanically blend the various solid ingredients, including effective amounts of the antimicrobial compound and abrasives, into a homogeneous powder.
Mouth washes or rinses prepared in accordance with ~-this invention will usually comprise effective amount of the antimicrobial compound dissolved in a suitably flavored liquid vehicle such as an aqueous alcoholic vehicle.
The lozenges or troches contemplated by this invention are prepared by mixing particles of the active ingredient with ;
mucilage and natural or artificial sweeteners and flavoring ;
agents. Gelatin and water is also an effective base for these candy-like products. Chewing gum can be prepared by the sub-stitution of a standard gum base for the mucilage. Suitable ~lO4~
bulking agents or fillers may be added to any of these edible products.
The oral preparations employed according to this invention may be prepared in accordance with the skill and practive of the prior art. The distinguishing feature of this invention is the inclusion of an effective amount of selected antimicrobial compositions to inhibit the formation of dental plaque and/or reduce the incidence of dental caries. These antimicrobial compositions may be incorporated into the oral preparation either as a substitute for or in addition to other anti-caries agents which have previously been discovered and employed by the prior art.
The antimicrobial compositions or combination of compositions of this invention should be present in the oral preparations in an amount sufficient to produce an effective concentration of the compounds in the mouth. Normally this involves the formation of oral preparations which contain or release the antimicrobial composition in the mouth at a concen- -tration of from about Q.03% to about 1%, preferably from about 0.075% to about 0.75%, and most preferably from about 0.1% to about 0.5%. The percentages being by weight. It will be apparent to those skilled in the art from a reading of this specification that the active ingredients identified according to the present invention will normally be used at lower concen- ;
trations when employed with another, complimentary active agent.
EXAMPLE I
The active ingredients of the present invention were tested at various concentrations in a thioglycollate broth medium inoculate with a known amount of cariogenic organism and were quantitativeIy compared with control cultures which did not contain the àntimicrobial compound. Additional cultures containing equivalent amounts of the major constituents of ?45~L7 pimento berry oil were also investigated but found to be less effective than the pimento berry oil itself as antimicrobials against cariogenic streptococci.
The method of testing consisted of inoculating 5 or 10 ml portions of the thioglycollate broth having added thereto 5%
sucrose by weight, a pinch of calcium carbonate and the active ingredient (except control), usually in an ethanol solution. The controls contained like amounts of ethanol. All tests were con-ducted at 37C. Counts were determined by plating suitable sub-1~ dilutions on Mitis Salivarius Agar (Difco).
The results are summari~ed in the Tables below.
Pimento Berry Oil Constituents (the numbers in parentheses indi-cate the weight percent of the indicated materials in pimento berry oil):

TABLE I
Inoculum: 2 x 107 (Strep mutans FA-l; organisms/ml) Acti~e Ingredients Conc. Count (wt.%) 30 min. 60 min. 24 hrs.

None - 2 x 107 2 x 107 4 x 108 Eugenol* (69) 0.1 2 x 107 4 x 1o6 8 x 104 Pimento Berry Oil 0.1 2 x 106 S x 105 7 x 103 - .

*Trademark (also comprises 90% of Bay Oil) ~ ', ~ "

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TABLE II
Innoculum: 3 x 107 (Strep mutans FA-1; organisms/ml) Active IngredientsConc. Count (wt.%) 30 min. 60 min. 24 hrs.

None - 4 x 107 4 x 107 5 x 108 Cineole (2.3) 0.1 2 x 107 3 x 107 9 x 10 Rhellandrine (1.0) 0.1 2 x 107 2 x 107 2 x 107 Pimento Berry Oil 0.1 8 x 106 9 x 106 7 x 106 .
TABLE III ~:
Inoculum: 1 x 106 (Strep mutans FA-l; organisms/ml) Active Ingredients Conc. (wt.%) Count after 24 hours None - 2 x 108 Myrcene (0.8) 0.1 6 x 107 Terpinolene (0.7) 0.1 6 x 107 Terpineol ( 2.7) 0.1 2 x 108 P-cymene (1.4) 0.1 6 x 107 Pimento Berry Oil 0.1 3 x 104 ~ - 6 -~ ~ '~ - .

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-~L0~4~7 TABLE IV
Inoculum: 3 x 107 (Strep mutans FA-l; organisms/ml) Active IngredientsConc. (wt.%) Count 6 hrs.24 hrs.

None - 7 x 10~101 Methyl Eugenol (8.8) 0.12 x 107 2 x 107 Eugenol* (69) 0.1 9 x 1059 x 103 Pimento Berry Oil 0.1 4 x 1049 x 102 *Trademark - 6 (a) -104~ 7 Pimento Berry Oil effecti~e against various organisms:

TABLE VII
Inoculum: 7 x 105 (L. fermenti: organisms/ml) - . .
Active Ingredient Conc. (wt. %)` Count after 1 hr.
.. . . _ _ ..
None - 7 x 10 Pimento Berry Oil 0.1 3 x 102 TABLE ~III
Inoculum: 1 x 106 (L. casei: organisms/ml) Active Ingredient Conc. (wt. %) Count a;fter 1 hr.
10 None - l x 10 Pimento Berry Oil 0.1 ~102 ::: :: : ,: ~, TABLE IX
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Exp. Active Conc. Original Inoculum After 24hrs.
No. Ingredient (wt.%) (Strep mutans FA-l; (organisms/ml) organisms/ml ; .
l Pimento 7 Berry Oil 0~1 3 x 10 4 x 106 Z Pimento Berry Oil 0.1 8 x 106 2 x 10 20 3 Pimento Berry Oil 0.1 2 x 107 6 x 102 .:

, TABLE X
Inoculum: 4 x 104 (Strep mutans SL-l; organisms/ml) .. ... .
Active Ingredient Conc. Count (wt.%) 30 min. - 60 min.
None 0.1 4 x 1044 x 104 Pimento Berry Oil 0.1 ~102 ~10 . . . .. _ ... _ _ _ TERPENELESS BAY OIL ;
TABLE XI
Inoculum: 5 x 107 (S. mutans FA-l; organisms/ml) 10 Active Ingredient Conc. Count (wt.%) 30 min. 60 min. 24hrs.
None - 6 x 107 5 x 1074 x 108 Terpeneless Bay Oil 0.15 x 1039 x 102 ~102 Pimento Berry Oil 0.13 x 1053 x 105 1 x 103 TABLE XII
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Active Conc. Inoculum S. Mutans 10 minO 20 min. ~
Ingredient (wt.%) Strain -None 3 x 107 FA-l 3 x 1073 x 107 Terpeneless Bay Oil 0.1 3 x 107 FA-l 3 x 1052 x 10 None 6 x 10 SL-l 6 x 1074 x 107 ;
Terpeneless ~ 2 Bay Oil 0.1 6 x 107 SL-l ~10 < 102 None 2 x 107 E-49 2 x 1072 x 107 Terpeneless 5 Bay Oil 0.1 2 x 107 E-49 1 x 108 x 103 - : - ..
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Effect of Terpeneless Bay Oil and;Pimento Berry ~il on Lactobacilli:

TABLE XIII

Active Con. Inoculum Lactobacilli 10min. 20min.
Ingredient ~(wt.~%) -- Species None 2 x 105 - L. fermenti 2 x 105 2 x 105 Pimento Berry Oil 0.1 2 x 105 ~ 2 x 102 2 x 102 Terpeneless Bay Oil 0.1 2 x 105 " " l x 102 1o2 None 1 x 10 LD casei l x 106 l x 10 PimentO 6 Berry Oil 0.1 l x 10 " " 3 x 102 10 Terpeneless 6 2 Bay Oil 0.1 1 x 10 " " 10 102 ;

EX~MPLE II
Dextran accumulation by cariogenic strep mutans F~ l on nichrome wires, and its prevention by Pimento Berry Oil.

A technique has been developed by Jordan & Keyes and others in which cariogenic streptococci deposit dextran on nichrome wires. Usually it takes 10 successive transfers to get a thick coating of dextran. This is what happened in the control wires. The test wires were placed in activeIy growing culture of Strep mutans FA-l, removed and immersed three times a day for short periods as given in the Tables in Pimento Berry Oil solu-tions in thioglycolate broth containing ethanol.
Results may be seen from Tables XIV and XV.

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: TABLE ~IV
Treatment 5 minutes, 3 times per day Immersion Solution Deposit after. 10 days . - - .
.
Control ~Saline) Meavy dextran deposition 5% Ethanol ~eavy dextran deposition 0.17% Pimento Berry Oil +5% Ethanol Trace dextran deposition TABLE XV
Treatment 1 minute, 3 times per day - :
10 Immersion Solution Deposit after 10 days ;:
Control (Saline) Heavy dextran deposition 10% Ethanol Heavy dextran deposition 0.17% Pimento Berry Oil :
+10% Ethanol Moderate dextran deposition -0.25% Pimento Berry Oil : .
+10~ Ethanol Light dextran deposition ;~:
0.30% Pimento Berry Oil .
+10% Ethanol No dextran deposition :

The results show that dilute Pimento Berry Oil ..
solutions severly retarded or completely eliminated dextran ::
formation in this Example, even though contact time and removal from the actively growing culture was only 1 x 3 or 5 x 3 minutes ...
a day simulating use in normal preparation. It being noted that .;
the ethanol solution by its.elf gives no noticable improvement. :
The above Examples and explanations are for the purpose of teaching those skilled in the art how to practice the prasent invention. Upon reading this disclosure, those skilled in the '`~ .

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~ ;417 art will become aware of a number of modifications and variations.
It is contemplated that these modifications and variations be included within the scope of the present invention which is defined by the claims.

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Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
A composition for reducing the incidence of dental caries comprising a chewing gum or lozenger base containing from about 0.03% to about 1.0% of an antimicrobial compound selected from the group consisting of pimento berry oil, terpeneless bay oil and combinations thereof, said composition containing enough of one or more of said compounds to produce an effective concentra-tion of said compound in the mouth to be effective in inhibiting the formation of dental plaque and/or dental caries.