Note: Descriptions are shown in the official language in which they were submitted.
J. 370/1
ORAL COMPOSITIONS
_
This invention relates to compositions for the care
of the oral cavity.
The efficacy of fluorine in the prevention of
dental caries is well established (see for example
US Patents 3 029 191, 3 070 510 and 3 227 617). The
acceptance of fluoride ions as an anticariogenic agent is
based essentially on the observation that among the many
topical agents that have been tested in clinical ~rials
only those that contain fluorine have been effective in
reducing caries. Fluorine-free salts tested have not
prevented caries formation.
~ It is known that sodium hexafluorostannate
(Na~SnF6) applied topically to the teeth has a caries
inhibiting effect (Caries Res. 3, 315-325, 196~).
We have now found that stannic ammonium fluoride,
Sn(NH4)2F6, (which may also be called ammonium
hexafluorostannate),as well as having an anti-caries effect
also has a plaque inhibiting effect (which has not bee~
reported for sodium hexafluorostannate) and furthermore
that stannic ammonium hexafluorostannate has an important
practical advantage over the use of sodium
3 hexafluorostannate in that it has a significally better
taste than the sodium compound~
` -:lE3 21
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Accordingly the invention provides an oral
composition having anti-caries and anti-plaque
activity comprising O.Ol to 3% by weight of stannic
ammonium fluoride tSn(NH4)2F~
The synthesis of Sn(NH~)2F6 is described in
J.Am.Chem.Soc~ 80, 2662, 1958.
In the preparation of therapeutic or prophylactic
oral compositions incorporating Sn(NH4)2F6, a
suitable carrier or oral media well known in the art is
used. Adjuvants such as colouring agents, flavours,
humectants, abrasives, detergents, preservati~es, I!
emollients and the like and other therapeutic agents
compatible with Sn(NH4)2F6 may also be included.
The oral composition is preferably in the form of a
toothpaste or mouthwash. A particularly suitable amount
of the Sn(NH4)2F6 is such as to provide from lO00 to
l500 ppm of fluoride ion. However, the amount may
conveniently range from lO0 to 3000 ppm.
The following Experiments and Examples illustrate
the invention. Percentages are by weight~
The Sn(NH4)2~6 employed in the following
experiments was synthesised according to the method of
Haendler and Johnson (J~Am.Chem.Sec. 80, 2662, 1958).
The analytical details were as follows:
Theoretical % _a~tical %
Sn 44.18 45.64
NH413.41 12.65
F 42.41 43.l4
Cariogenic Bacteria used for testing the effect of
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Sn(NH4)2F6 were ~ s mutans (strains coded
6715 and OMZ-176), Streptococcus_sanguis (strains coded
10556 and 10557), Streptococcus salivarius (strains coded
SS4 and H257), and Lactobacillus casei.
All of the above organisms were maintained as lyophilised
cultures until the time for use.
An aqueous solution of Sn(NH4)2F6 has a pH of
about 3.8 as compared to a pH of 3.0 for SnF2. This
higher pH characteristic eliminates some of the formulation
problems encountered with the strong acid effect of SnF2
The preferred pH of oral compositions containing
Sn~NH4)2F6 is from 3.5 to 8Ø A 1000 ppm F
solution of Sn(NH4~2F6 was sta~le- It did not
become hazy on standing after several weeks. In contrast,
a SnF2 solution developed turbidity, probably due to
oxy-fluoride formation, after 24 hours at room temperature.
SnF2 at conc~ntrations equivalent to 1000 ppm and
2~ 2500 ppm released, respectively,80% and 45% of the
available F. Sn(NH~)2F6 displayed the same
. ionisation values as SnF2. The corresponding values for
Na2SnF6 are 73% and 38~, respectively. Thus
Na2SnF6 is less ionised than Sn(NH4)2F6,
Sn(NH4)~F6 is significantly better tasting
han a2 n 6 A comparative test was carried out with
a panel of 3 assessors, and tasting (20 sec. rinse with 10
ml of test solution containing 1000 ppm F ) was performed
3 with coded solutions or on a blind basis~ The finding
that Sn(NH4)2F6 had a significantly less metallic
taste than Na2SnF6 was the unanimous decision of the
three judges. Sn(NH~)2F6 was also much less
astringent and metallic tasting than the uncomple~ed
fluoride salt SnF2 at equal molar concentratiOnS.
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A similar blind test was conducted to compare the taste of
Sn(NH4)2F6 with that of SnF25 This showed that
Sn(NH4)2F6 had a significantly less metallic taste
than SnF2 and this was the unanimous decision of the
three judges.
It is generally agreed that oral bacteria are
responsible for tooth decay. Therefore, a reduction of the
cariogenic flora usually results in a decrease in caries
formation. The inhibitory action of the test compounds was
determined by adding each salt, at known concentrations, to
a culture of cariogenic bacteriaO After 24 hours at 37C
bacterial growth was monitored as a change in optical
density. A dose response curve (concentration of salt vs.
~rowth) for each cornpound against each bacterial isolate
was plotted in order to obtain the concentration of test
- agent which would cause a 50% inhibition in growth (ID/50).
This is a useful ranking index since it is not always
possible to obtain complete inhibition with weak germicidal
agents. Only those compounds which were able to elicit an
ID/50 response were considered as inhibitory agents.
The ~edium used for ba~terial growth experiments
. was Trypticase Soy Broth (B.B.L.: Baltimore Biological
Labs. r Baltimore, MD) supplemented with 0.1% Tween 80
(the word Tween is a trade mark) and 0.05~ sodium
thioglycollate. The test organisms, as lyophilised cells,
were grown overnight in 50 mls of growth medium in a vacuum
desiccator with an atmosphere of 97% CO2/3% H2 at 35Co
T~lese cultures were then used at a 0.2~ inoculum to prepare
second stage seed flasksO The test media (lOml)
consisting of growth medium plus the potential inhibitors,
contained in 16 x 12Q mm screw top test tubes, were
inoculated with the second stage seed cultures to given -an
absorbancy reading of 0.05~ Immediately after inoculation
the cultures were incubated for 24 hours under anaerobic
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conditions.
The growth medium was sterilised by autoclaving,
whereas the poten~ial inhibitors (as aqueous solutions)
were sterilised by filtering each solution separately
through a Millipore membrane (0.22 /u).
Absorbance at 600 nm versus a medium control was
used as a measure of growth on a Beckman Model B
spectrophotometer. All absorbancy readings were
determined in 16 mm x 120 mm Kimax test tubes. This
instrument was linear to 0.60 OD units; thus, all
cultures displaying values above this range were diluted
with the control, accordingly.
TABLE I
INHIBITICN OF BACT~RIAL ~ROWTH
I 50 (mM/L)
20S.mutans S.salivarius ~ L.casei
6715 _Z~176 SS4 H-257 10556 10557
Salts
,
* SnCl2 2.26 3.68 1.45 3.64 1.27 1088 3-6.0
* SnF2 1.50 2.28 2.45 0.74 0.44 0.84 2~97
* ~n(NH4~6 1~20 1.43 1.65 0.40 0.22 0.39 2.53
* NaF 7.3 16.30 13.40 3.77 1.18 1.82 >12.00
The above values are the means of triplicate experiments.
3 The results show that Sn(NH~)2F~ was more
inhibitory than the non-fluoride salts and NaF, with no
apparent changes in specificities. The ID/50 values,
recalculated as ppm F , again show (Table II) that
Sn(NH4)2F6 is over-all more active than NaF.
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TABLE II
INHIBITION OF BACTERIAL GROWTH BY FLUORINE SALTS
ID/50 (ppm F)
S~mutans SOsalivarius S.sanguis L.casei
6715 OMZ-176 SS4H-257 10556 10557
Salts
NaF 138 309 255 72 22 35 352
* SnF2 56 87 93 29 17 32 113
~n(~H4~6 1~7 163 188 46 25 45 288
It should be noted that Sn(NH4)2F6, which is
the stannic form of tin~ was less active than the stannous
form SnF2.
Dental plaque is a film on the surface of teeth.
This layer is the result of bacterial growth and is
composed chiefly of microorganisms, proteinaceous materials
and microbial by~products, such as glucans and organic
acids~ Plaque is not only primarily responsible for
caries formation but it is also implicated in gingival
diseases. Because the results described herein above have
demonstrated that Sn(NH4)2F6 possesses antibacterial
activityl it is obvious that Sn(N~4)2F6 will also
reduce plaque formation.
The following are examples of a toothpaste and a
mouthwash composition of the invention.
3o
5i9
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EXAMPLE I
~ The following is an example of a toothpaste
composition according to the invention -
Silica xerogel 13.00
Silica aerogel 22.00
Sorbitol (70% solution)41.50
Sn(NH4)2F6 0.24
Sodium lauryl sulphate7.00
Colour 0.04
Flavour 3.00
Sodium Saccharin 0.12
Sodium Benzoate 0O06
Titanium Dioxide 0-35
Glycerine 7O53
Water Balance to 100%
-
EXAMPLE 2
The following is an example of a mouthwash~
composition according to the present invention.
, Ethanol 15.00
Propylene Glycol 10.00
Glycerol 12.00
Flavour, Colour 0.90
Polyoxyethylene (20)
monolaurate 2.10
Sodium lauryl sulphate 0.33
Sn(NH4)2F6 0.024
Buffer 18.00
Hydrochloric acid (to pH 4.1) q s
Water Balance to 100%
Although the examples herein show the use of
Sn(NH4)2F6 in dentifrice and mouthwash preparations,
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the compounds of the present invention may also be
incorporated in other oral preparations or formulations
such as for example chewing gums and lozenges.
