Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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
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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
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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
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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
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*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
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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)
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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
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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
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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
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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
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10 Immersion Solution Deposit after 10 days
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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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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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