Note: Descriptions are shown in the official language in which they were submitted.
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DENTIFRICE COMPOSITIONS WITH IMPROVED FLUORIDE STABILITY
FIELD OF THE INVENTION
The present invention relates to dentifrice composition having a fluoride ion
source.
BACKGROUND OF THE INVENTION
Dentifrice compositions are well known for dental and oral hygiene care. High
water
(e.g., >45 wt%) and high carbonate (e.g., >25 wt%) formulation chassis are a
cost effective for
many markets and consumers. The use of linear sulfated polysaccharide (e.g.,
carrageenan) has
[0 been reported in dentifrice compositions as a thickening agent. However,
this formulation
chassis sometimes has fluoride ion stability issues that often exacerbated
when there are high
temperatures and/or long distribution times such as in some developing
markets. Fluoride, and
its associated benefits, is critical for a user's experience and product
acceptance. There is a need
to provide dentifrice formulations having improved fluoride ion stability.
[5
SUMMARY OF THE INVENTION
The present invention is based, in part, on the surprising observation that
soluble fluoride
ion stability is increased in high water and high carbonate dentifrice
formulations with the use of
carrageenan. Furthermore, this fluoride ion stability effect is further
enhanced under pH
W conditions that are greater than pH 8, preferably greater than pH 8Ø
Yet still further, of the
carrageenans, Lambda- carrageenan appears to be the best performing one for
fluoride ion
stability.
Accordingly, an advantage of the present invention is soluble fluoride
stability over time.
The advantages are observed in accelerated high temperature (e.g., 60 C for 6
weeks) as well as
long term ambient conditions (e.g., 30 C for 1 year).
One aspect of the invention provides for dentifrice composition comprising:
(a) 45% to 75%
water, preferably 50% to 60% water, by weight of the composition; (b) 25% to
50%, preferably
27% to 47%, preferably 27% to 37% of a calcium-containing abrasive by weight
of the
composition, preferably wherein the calcium-containing abrasive is calcium
carbonate; (c)
30 0.0025% to 2%, preferably from 0.5% to 1.5% of a fluoride ion source by
weight of the
composition, preferably wherein the fluoride ion source is sodium
monofluorophosphate; (d)
0.01%% to 7%, preferably from 0.1% to 6% of a linear sulfated polysaccharide
by weight of the
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WO 2015/172651 PCT/CN2015/077634
composition, preferably wherein the linear sulfated polysaccharide is a
carrageenam and (e) pH
greater than 8.0, preferably greater than 8.5. more preferably at or greater
than pH 9.
Another aspect of the invention provides a dentifrice composition comprising:
(a) 45% to
75%, preferably 50% to 60% water by weight of the composition; (b) 25% to 50%,
preferably 27%
to 47%, preferably 27% to 37% of a calcium-containing abrasive by weight of
the composition,
preferably wherein the calcium-containing abrasive comprises calcium
carbonate; (c) 0.0025% to
2%, preferably from 0.5% to 1.5% of a fluoride ion source by weight of the
composition.
preferably the fluoride ion SOUSA: comprises sodium monolluorophosphate; and
(d) 0.01% ic to
7%, preferably from 0.1% to 6% of a Lambda-carrageenan by weight of the
composition.
1.0 Yet another
aspect of the invention provides a method of treating tooth enamel comprising
the step of brushing teeth with an oral care composition described herein.
While the specification concludes with claims that particularly point out and
distinctly claim
the invention, it is believed the present invention will be better understood
from the following
description.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 describes dentifrice formulations of Examples 1-15, wherein Examples
1, 12, 13,
14, and 15 are control formulations.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
The term "orally acceptable carrier" as used herein means a suitable vehicle
or ingredient,
which can be used to form and/or apply the present compositions to the oral
cavity in a safe and
effective manner.
?.5 The term
"comprising" as used herein means that steps and ingredients other than those
specifically mentioned can be added. This term encompasses the terms
"consisting or' and
"consisting essentially of." The compositions of the present invention can
comprise, consist of,
and consist essentially of the essential elements and limitations of the
invention described herein,
as well as any of the additional or optional ingredients, components, steps,
or limitations
described herein.
The term "effective amount" as used herein means an amount of a compound or
composition sufficient to induce a positive benefit, an oral health benefit,
and/or an amount low
enough to avoid serious, side effects. i.e.. to provide a reasonable benefit
to risk ratio, within the
2
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sound judgment of a skilled artisan. In one embodiment, "effective amount"
means at least 0.01%
of the material, by weight of the composition, alternatively at least 0.1%.
The term "dentifrice" as used herein means paste, gel, powder, tablets, or
liquid
formulations, unless otherwise specified, that are used to clean the surfaces
of the oral cavity.
The term "teeth" as used herein refers to natural teeth as well as artificial
teeth or dental
prosthesis.
All percentages, parts and ratios are based upon the total weight of the
compositions of the
present invention, unless otherwise specified. All such weights as they
pertain to listed
ingredients are based on the active level and, therefore do not include
solvents or by-products
that may be included in commercially available materials, unless otherwise
specified. The term
"weight percent" may be denoted as "wt%" herein. All molecular weights as used
herein are
weight average molecular weights expressed as grams/mole, unless otherwise
specified.
As used herein, the articles including -a" and "an" when used in a claim, are
understood to
mean one or more of what is claimed or described.
As used herein, the terms "comprise". "comprises", "comprising", "include",
"includes",
"including", "contain", "contains", and "containing" are meant to be non-
limiting, i.e., other
steps and other sections which do not affect the end of result can be added.
The above terms
encompass the terms "consisting of' and "consisting essentially of'.
As used herein, the words "preferred", "preferably" and variants refer to
embodiments of the
10
invention that afford certain benefits, under certain circumstances. However,
other embodiments
may also be preferred, under the same or other circumstances. Furthermore, the
recitation of one
or more preferred embodiments does not imply that other embodiments are not
useful, and is not
intended to exclude other embodiments from the scope of the invention.
Water
!,5 The
compositions of the present invention comprise herein from 45% to 75%, by
weight of
the composition of water. In one embodiment, the composition includes from 40%
to 70%,
alternatively from 45% to 65%, alternatively from 40% to 60%, alternatively
from 50% to 70%,
alternatively from 50% to 60 %, alternatively from 45% to 55%, alternatively
from 55% to 65%,
alternatively from 50% to 60%, alternatively about 55%, alternatively
combinations thereof, of
30
water by weight of the composition. The water may be added to the formulation
and/or may
come into the composition from the inclusion of other ingredients. Preferably
the water is USP
water.
Calcium-containing abrasive
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The compositions of the present invention comprise from 25% to 50% by weight
of a
calcium-containing abrasive, wherein the calcium-containing abrasive is
selected from the group
consisting of calcium carbonate, dicalcium phosphate, tricalcium phosphate,
calcium
orthophosphate, calcium metaphosphate, calcium polyphosphate, calcium
oxyapatite, sodium
carbonate, and combinations thereof. In preferred embodiment, the
composition comprises
from 25% to 60%, more preferably from 25% to 50%, even more preferably from
25% to 40%,
yet even more preferably from 26% to 39%, alternatively from 27% to 47%,
alternatively from
27% to 37%, alternatively from 30% to 35%, alternatively from 30% to 34%,
alternatively
combinations thereof, of a calcium-containing abrasive by weight of the
composition.
l0 In
yet still a further preferred composition contains calcium-containing abrasive
at the
previously indicated weight percentage, wherein the calcium-containing
abrasive is a calcium
carbonate, and wherein the calcium carbonate has: a D50 particle size range
from 2 microns to 7
microns, preferably from 3 microns to 6 microns, more preferably from 3.4
microns to 5.8
microns; or D90 from 8 microns to 15 microns, preferably from 9 microns to 14
microns, more
preferably from 9.2 microns to 13.5 microns; or D98 range from less than 28
microns, preferably
from 1 micron to less than 27 microns, more preferably less than 26 microns or
from 1 micron to
less than 26 microns. More preferably the calcium carbonate has a particle
size range at the
aforementioned D50 and D90 ranges; even more preferably at the aforementioned
D50, D90 and
D98 ranges. Surprisingly, it is believed that having calcium carbonate at
these aforementioned
10
particle size distribution ranges may increase fluoride stability benefits.
Fluoride stability may
be measured as described in herein.; and generally in China's National
Standard Method
GB 8372-2008.
The term "D50" means, in particle size distribution measurements, the mass-
median-
diameter, considered to be the average particle size by mass. That is, the D50
is the size in
)-5
microns that splits the distribution with half above and half below this
diameter by mass. The
term D90 similarly means the size in microns that splits 90 percent of the
distribution below the
D90 by mass. And the similarly the term D98 means the size in microns that 98
percent of the
distribution below the D98 by mass.
The particle size of calcium carbonate (as a raw material) is measured by
using a laser
30
scattering particle sizing instrument (e.g., Bettersize BT9300H from DanDong
Better Instrument,
China). Generally, the laser scattering technique works by measuring the light
diffracted from
particulates as they pass through a laser beam. Particulates scatter light at
an angle that is
directly related to their size. Accordingly, the Bettersize BT9300H uses the
light scattering
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pattern associated with a sample to calculate particle size distributions. The
methods of ISO
13320-1-1999 are followed. Briefly, calcium carbonate raw material is pre-
dispersed in
deionized water (DI-water"). And a volume of calcium carbonate slurry is
transferred to
sampling cell, which is filled with DI-water as dispersion solution. The
particles of calcium
.. carbonate are well dispersed by re-circulation and ultrasonication while
particle size
measurements are being obtained.
In one embodiment, the calcium-containing abrasive is calcium carbonate. In a
preferred
embodiment, the calcium-containing abrasive is selected from the group
consisting of fine
ground natural chalk, ground calcium carbonate, precipitated calcium
carbonate, and
[0 combinations thereof. In a more preferred embodiment, the calcium-
containing abrasive is
selected from fine ground natural chalk, ground calcium carbonate, and
combinations thereof (at
the aforementioned weight percentage ranges for calcium-containing abrasives;
and having the
aforementioned D50, D90, and D98 measurements).
Fine ground natural chalk (FGNC) is one of the more preferred calcium-
containing
abrasives useful in the present invention. It is obtained from limestone or
marble. FGNC may
also be modified chemically or physically by coating during milling or after
milling by heat
treatment. Typical coating materials include magnesium stearate or oleate. The
morphology of
FGNC may also be modified during the milling process by using different
milling techniques, for
example, ball milling, air-classifier milling or spiral jet milling. One
example of natural chalk is
10 described in WO 03/030850 having a medium particle size of 1 to 15 pm
and a BET surface area
of 0.5 to 3 m2/g. The natural calcium carbonate may have a particle size of
325 to 800 mesh,
alternatively a mess selected from 325, 400 600, 800, or combinations thereof;
alternatively the
particle size is from 0.1 to 30 microns, or from 0.1 to 20 microns, or from 5
to 20 microns
In one embodiment, the composition of the present invention is free or
substantially free of
)-5 silicate.
PEG
The compositions of the present invention may comprise polyethylene glycol
(PEG), of
various weight percentages of the composition as well as various ranges of
average molecular
weights. In one aspect of the invention, the compositions have from 0.1% to
15%, preferably
30 from 0.2% to 12%, more preferably from 0.3% to 10%, yet more preferably
from 0.5% to 7%,
alternatively from 1% to 5%, alternatively from 1% to 4%, alternatively from
1% to 2%,
alternatively from 2% to 3%, alternatively from 4% to 5%, or combinations
thereof, of PEG by
weight of the composition. In another aspect of the invention, the PEG is one
having a range of
5
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average molecular weight from 100 Daltons to 1600 Daltons, preferably from 200
to 1000,
alternatively from 400 to 800, alternatively from 500 to 700 Daltons,
alternatively combinations
thereof. PEG is a water soluble linear polymer formed by the addition reaction
of ethylene oxide
to an ethylene glycol equivalent having the general formula is: H-(OCH2CH2)õ-
OH. One
supplier of PEG is Dow Chemical Company under the brand name of CARBOWAXTM.
Sweetener
The oral care compositions herein may include a sweetening agent. These
include
sweeteners such as saccharin, dextrose, sucrose, lactose, maltose, levulose,
aspartame, sodium
cyclamate, D-tryptophan, dihydrochalcones, acesulfame, sucralose, neotame, and
mixtures
[0 thereof. Sweetening agents are generally used in oral compositions at
levels of from 0.005% to
5%, by weight of the composition, alternatively 0.01% to 1%, alternatively
from 0.1% to 0.5%,
alternatively combinations thereof.
Fluoride ion source
The compositions may include an effective amount of an anti-caries agent. In
one
embodiment, the anti-caries agent is a fluoride ion source. The fluoride ion
may be present in an
amount sufficient to give a fluoride ion concentration in the composition at
25 C. and/or in one
embodiment can be used at levels of from about 0.0025% to about 5% by weight
of the
composition, alternatively from about 0.005% to about 2.0% by weight of the
composition, to
provide anti-caries effectiveness. Examples of suitable fluoride ion-yielding
materials are
10 disclosed in U.S. Patent Nos. 3,535,421, and 3,678,154. Representative
fluoride ion sources
include: stannous fluoride, sodium fluoride, potassium fluoride, amine
fluoride, sodium
monofluorophosphate, and zinc fluoride. In one embodiment the dentifrice
composition contains
a fluoride source selected from stannous fluoride, sodium fluoride, and
mixtures thereof. In one
embodiment, the fluoride ion source is sodium monofluorophosphate, and wherein
the
)-5 composition comprises 0.0025% to 2% of the sodium monofluorophosphate
by weight of the
composition, alternatively from 0.5% to 1.5%, alternatively from 0.6% to 1.7%,
alternatively
combinations thereof. In another embodiment, the composition comprises from
0.0025% to 2%
of a fluoride ion source by weight of the composition.
PH
30 The pH of the dentifrice composition may be greater than pH 7.8, or from
pH 8 to 13, more
preferably from 9 to 12, alternatively greater than pH 8, alternatively
greater than 9, alternatively
from 9 to 11, alternatively from 9 to 10, or combinations thereof.
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A method for assessing pH of dentifrice is described. pH is measured by a pH
Meter with
Automatic Temperature Compensating (ATC) probe. The pH Meter is capable of
reading to
0.001 pH unit. The pH electrode may be selected from one of the following (i)
Orion Ross Sure-
Flow combination: Glass body - VWR #34104-834/Orion #8172BN or VWR#10010-
772/Orion
#8172BNWP; Epoxy body - VWR #34104-830/Orion #8165BN or VWR#10010-770/Orion
#8165BNWP; Semi-micro, epoxy body - VWR #34104-837/Orion #8175BN or VWR#10010-
774/Orion #3175BNWP; or (ii) Orion PerpHect combination:VWR #34104-843/Orion
#8203BN
semi-micro, glass body; or (iii) suitable equivalent. The automatic
temperature compensating
probe is Fisher Scientific, Cat #13-620-16.
l0 A 25% by weight slurry of dentifrice is prepared with deionized
water, and thereafter is
centrifuged for 10 minutes at 15000 rotations-per-minute using a SORVALL RC
28S centrifuge
and SS-34 rotor (or equivalent gravitational force, at 24149g force). The pH
is assessed in
supernatant after one minute or the taking reading is stabilized. After each
pH assessment, the
electrode is washed with deionized water. Any excess water is wiped with a
laboratory grade
tissue. When not in issue, the electrode is kept immersed in a pH 7 buffer
solution or an
appropriate electrode storage solution.
pH modifying agent
The dentifrice compositions herein may include an effective amount of a pH
modifying
agent, alternatively wherein the pH modifying agent is a pH buffering agent.
pH modifying
10 agents, as used herein, refer to agents that can be used to adjust
the pH of the dentifrice
compositions to the above-identified pH range. pH modifying agents may include
alkali metal
hydroxides, ammonium hydroxide, organic ammonium compounds, carbonates,
sesquicarbonates,
borates, silicates, phosphates, imidazole, and mixtures thereof. Specific pH
agents include
monosodium phosphate (monobasic sodium phosphate), trisodium phosphate (sodium
phosphate
!,5 tribasic dodecahydrate or "TSP"), sodium benzoate, benzoic acid,
sodium hydroxide, potassium
hydroxide, alkali metal carbonate salts, sodium carbonate, imidazole,
pyrophosphate salts,
sodium gluconate, lactic acid, sodium lactate, citric acid, sodium citrate,
phosphoric acid. In one
embodiment, 0.01% to 3%, preferably from 0.1% to 1% of TSP by weight of the
composition,
and 0.001% to 2%, preferably from 0.01% to 0.3% of monosodium phosphate by
weight of the
30 composition is used. Without wishing to be bound by theory, TSP and
monosodium phosphate
may also have calcium ion chelating activity and therefore provide some
monofluorophosphate
stabilization (in those formulations containing monofluorophosphate).
Anti-calculus agent
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The dentifrice compositions may include an effective amount of an anti-
calculus agent,
which in one embodiment may be present from about 0.05% to about 50%, by
weight of the
composition, alternatively from about 0.05% to about 25%, alternatively from
about 0.1% to
about 15% by weight of the composition. Non-limiting examples include those
described in US
2011/0104081 Al at paragraph 64, and those described in US 2012/0014883 Al at
paragraphs 63
to 68, as well as the references cited therein. One example is a pyrophosphate
salt as a source of
pyrophosphate ion. In one embodiment, the composition comprises tetrasodium
pyrophosphate
(TSPP) or disodium pyrophosphate or combinations thereof, preferably 0.01% to
2%, more
preferably from 0.1% to 1% of the pyrophosphate salt by weight of the
composition. Without
wishing to be bound by theory, TSPP may provide not only calcium chelating
thereby mitigating
plaque formation, but also may also provide the additional benefit of
monofluorophosphate
stabilization (in those formulations containing monofluorophosphate).
Surfactant
The dentifrice compositions herein may include a surfactant. The surfactant
may be selected
from anionic, nonionic, amphoteric, zwitterionic, cationic surfactants, or
mixtures thereof. The
composition may include a surfactant at a level of from about 0.1% to about
10%, from about
0.025% to about 9%, from about 0.05% to about 5%, from about 0.1% to about
2.5%, from about
0.5% to about 2%, or from about 0.1% to about 1% by weight of the total
composition. Non-
limiting examples of anionic surfactants may include those described at US
2012/0082630 Al at
10 paragraphs 32, 33, 34, and 35. Non-limiting examples of zwitterionic or
amphoteric surfactants
may include those described at US 2012/0082630 Al at paragraph 36; cationic
surfactants may
include those described at paragraphs 37 of the reference; and nonionic
surfactants may include
those described at paragraph 38 of the reference. In one embodiment the
composition comprises
0.1% to 5%, preferably 0.1% to 3%. alternatively from 0.3% to 3%,
alternatively from 1.2% to
)-5 2.4%, alternatively from 1.2% to 1.8%, alternatively from 1.5 % to
1.8%, alternatively
combinations thereof, of the anionic surfactant sodium lauryl sulfate (SLS) by
weight of the
composition.
Thickening agent
The dentifrice compositions herein may include one or more thickening agents.
A
30 thickening agent may be used in an amount from about 0.01% to about 15%,
or from about 0.1%
to about 10%, or from about 0.1% to about 5%, by weight of the composition.
Non-limiting
examples may include those described in US 2008/0081023 Al at paragraphs 134
to 137, and the
references cited therein.
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In embodiment, the composition comprises a linear sulfated polysaccharide as a
thickening
agent. Carrageenans or carrageenins are one example of a linear sulfated
polysaccharide.
Generally, carrageenans can vary based upon the degree of sulfation that
include: Kappa-
carrageenan, Iota-carrageenan, and Lambda-carrageenan. Combinations of
carrageenans can be
used. In one embodiment, the composition contains from 0.1% to 3% a linear
sulfated
polysaccharides by weight of the composition, preferably from 0.5% to 2%,
alternatively from
0.6% to 1.8%, alternatively combinations thereof. In one embodiment, Iota-
carrageenan is used.
In one embodiment, the composition comprises a silica agent, preferably a
thickening silica
obtained from sodium silicate solution by destabilizing with acid as to yield
very fine particles.
[0 One commercially available example is ZEODENT branded silicas from Huber
Engineered
Materials (e.g., ZEODENT 103, 124, 113 115, 163, 165, 167). In one
embodiment, the
composition comprising from 0.5% to 5% by weight of the composition of a
silica agent,
preferably from 1% to 4%, alternatively from 1.5% to 3.5%, alternatively from
2% to 3%,
alternatively from 2% to 5% alternatively from 1% to 3%, alternatively
combinations thereof by
weight of the composition.
In one embodiment, the composition comprises a carboxymethyl cellulose
("CMC"). CMC
is prepared from cellulose by treatment with alkali and monochloro-acetic acid
or its sodium salt.
Different varieties are commercially characterized by viscosity. One
commercially available
example is AqualonTm branded CMC from Ashland Special Ingredients (e.g..
Aqualonlm 7H3SF;
AqualonTm 9M35F AqualonTm TM9A; Aqualonrm TM12A). In one embodiment, the
composition contains from 0.1% to 3% of a CMC by weight of the composition,
preferably from
0.5% to 2%, alternatively from 0.6% to 1.8%, alternatively combinations
thereof by weight of the
composition.
In yet another embodiment, the thickener agents may comprise liner sulfated
polysaccharide
)-5 (e.g., carrageenans), CMC, and preferably also a thickening silica for
purposes of cost savings
while achieving the right balancing of viscosity and elasticity.
In one embodiment, the
composition comprises a thickener comprising: (a) 0.01% to less than 1.4 %,
preferably from 0.1 %
to 1.3%, more preferably from 0.5% to 1.3% of a carrageenan by weight of the
dentifrice
composition; and (d) greater than 0.4 wt% to 2 wt%, preferably from 0.5% to
1.8%, more
30 preferably from 0.6% to 1.8% of a carboxymethyl cellulose (CMC) by
weight of the dentifrice
composition. In yet another embodiment, the aforementioned thickener further
comprises 0.5%
to 5%, preferably 1% to 4%, of a thickening silica by weight of the dentifrice
composition.
Low or Free Humectants
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WO 2015/172651 PCT/CN2015/(J77634
The compositions herein may be substantially free or free of humectants,
alternatively
contain low levels of humectanis. The term "humectant." for the purposes of
present invention,
include edible polyhydric alcohols such as glycerin, sorbitol. xylitol,
butylene glycol. propylene
glycol, and combinations thereof. In one embodiment, the humectant is selected
from sorbitol,
glycerin, and combinations thereof. In yet another embodiment, the humectant
is sorbitol. In
one embodiment, the composition comprises from 0% to less than 20% of
humeetants by weight
of the composition, preferably from 0% to 10%. alternatively from 0% to 5%,
alternatively from
0% to 3%, alternatively from 0% to 2%, alternatively from 0% to 1%,
alternatively less than
20%. or less than 19%, 18%, 15%, 12%. 8%, 7%, 6%, 4%, 3%, 2%, 1%, or less than
0.5%; or
greater than 1%, or greater than 2%, 5%, 10%, or 15%; or combinations thereof,
by weight of the
composition. In yet another embodiment, the composition contains less than 20%
of sorbitol by
weight of the composition.
In an alternative embodiment, the compositions of the present invention
comprise a
humectant, preferably from 1% to 13% by weight of the composition.
Colorant.
The compositions herein may include a colorant. Titanium dioxide is one
example of a
colorant. Titanium dioxide is a white powder which adds opacity to the
compositions. Titanium
dioxide generally can comprise from about 0.25% to about 5%, by weight of the
composition.
Flavorant
The compositions herein may include from about 0.001% to about 5%,
alternatively from.
about 0.01% to about 4%, alternatively from about 0.1% to about 3%,
alternatively from about
0.5% to about 2%, alternatively 1% to 1.5%, alternatively 0.5% to 1%,
alternatively
combinations thereof, of a flavorant composition by weight of the composition.
The term.
fla.vorant composition is used in the broadest sense to include flavor
ingredients, or sensates. or
Z5 sensate agents, or combinations thereof. Flavor ingredients may include
those described in US
2012/0082630 Al at paragraph 39; and sensates and sensate ingredients may
include those
described at paragraphs 40 - 45. Excluded
from the definition
of composition is "sweetener" as described above).
DATA
Analytical Methods
The method for assessing soluble fluoride is described consistent with the
China's National
Standard Method GB8372-2008. Briefly, an ion-selective electrode (ISE) is used
to test soluble
fluoride in dentifrice. An example, of a fluoride ion meter is SARTORIUS PP-
50, but an
to
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equivalent may be used. The ion meter may be fitted with a fluoride-specific
ion electrode with a
single-junction reference electrode by Orion Research Inc., Cat. No. 9609BNWP,
but an
equivalent may be used. The sample is prepared by using a balance that is
accurate to the 0.0001
gram (g). 20 g of dentifrice is weighed into a tarred 50 mL plastic beaker and
then gradually
50mL of deionized water is added, while a magnetic stir bar is stirring in the
plastic beaker, until
the dentifrice is a completely disperse solution. The entire solution is
gently transferred to a
100mL plastic volumetric flask as to avoid generating foam (so the volume can
be measured
accurately), and deionized water is added to reach a total volume 100m1, and
then the solution is
shaken manually to form a slurry. The formed slurry is then transferred into
10 mL centrifuge
[0
tubes, and centrifuged for 10 minutes at 15000 rotations-per-minute (RPM) (at
24149g force) at
ambient temperature. Thereafter 0.5 mL of supernatant is transferred into a 2
mL mini-
centrifugal tube, and 0.7 mL of 4 mon HC1 is added to the tub. Then the tub is
capped, heated
in a 50 C water bath for 10 minutes. Thereafter the contents of the tub are
transferred to a 50
mL measuring flask. The following are also added to the flask: 0.7 mL of 4
mol/L NaOH to
neutralize the solution; 5 mL of citrate buffer solution (described further
below); deionized water
is added until a total volume of 50 mL is achieved in the flask; and then the
sample solution is
gently mixed. The aforementioned citrate buffer solution is prepared by
dissolving 100 g of
sodium citrate, 60 mL of glacial acetic acid, 60 g of NaCl, and 30g of NaOH,
all with water,
adjusting the pH to 5.0-5.5, and diluting the citrate buffer solution with
deionized water until a
10
total volume of 1000 mL is achieved. Turning back to the sample solution, the
entire 50 mL
solution is transferred to a 50 mL plastic beaker and the fluoride level is
assessed based on a
fluoride standard curve using the fluoride ion meter and electrode described.
The standard fluoride curve (w/w %) is prepared by accurately measuring 0.5
mL, 1.0 mL,
1.5 mL, 2.0 mL, and 2.5 mL fluoride ion standard solutions (100 mg/kg) into
five respective 50
!,5 mL
plastic measuring flasks. 5mL of citrate buffer solution (made as previously
described above)
into each respective flask, and then diluting each solution to the scale with
deionized water.
Thereafter, each solution is transferred into a 50 mL plastic beaker
respectively, measuring
potential E under magnetic agitation, recording potential values, and drawing
E-logc (wherein "c"
is a concentration) standard curve.
30 A
method for assessing pH of dentifrice is described. pH is measured by a pH
Meter with
Automatic Temperature Compensating (ATC) probe. The pH Meter is capable of
reading to
0.001 pH unit. The pH electrode may be selected from one of the following (i)
Orion Ross Sure-
Flow combination: Glass body - VWR #34104-834/Orion #8172BN or VWR#10010-
772/Orion
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PCT/CN2015/077634
#8172BNWP; Epoxy body - VWR #34104-830/Orion #8165BN or VWR#10010-770/Orion
#8165BNWP; Semi-micro, epoxy body - VWR #34104-837/Orion #8175BN or VWR#10010-
774/Orion #3175BNWP; or (ii) Orion PerpHect combination:VWR #34104-843/Orion
#8203BN
semi-micro, glass body; or (iii) suitable equivalent. The automatic
temperature compensating
probe is Fisher Scientific, Cat #13-620-16.
A 25% by weight slurry of dentifrice is prepared with deionized water, and
thereafter is
centrifuged for 10 minutes at 15000 rotations-per-minute using a SORVALL RC
28S centrifuge
and SS-34 rotor (or equivalent gravitational force, at 24149g force). The pH
is assessed in
supernatant after one minute or the taking reading is stabilized. After each
pH assessment, the
l0 electrode is washed with deionized water. Any excess water is wiped with
a laboratory grade
tissue. When not in issue. the electrode is kept immersed in a pH 7 buffer
solution or an
appropriate electrode storage solution.
Fig. 1 describes dentifrice formulations of Examples 1 ¨ 15. In turn, the
examples provide
the data summarizes in Table 1-5 below.
Table 1 below demonstrates that the higher amount of carrageenan that is used
in the
described formulations of examples 1-5, the better soluble fluoride ion
stability after being aged
at 6 weeks at 60 C. The relatively high temperature is used to exacerbate any
fluoride instability
over time. Examples 1-5, as described by the formulations of Figure 1, are
briefly summarized.
Examples 2-5 notable contain varying amounts of Iota-carrageenan (0.4 wt% to 2
wt%). except
10 Control E (i.e., Example 1) which does not contain any carrageenan.
Examples 1-5 contain the
humectant Sorbitol at 17 wt%. Examples 1-3 contain sodium carboxymethyl
cellulose while
examples 4 and 5 do not. Examples 1-4 contain thickening silica while example
5 does not.
Table 1:
Soluble
Soluble Fluoride Soluble Fluoride
Iota-C arra-
Example Fluoride (ppm, Drop (ppm,
geenan (wt% )
(ppm, Day 1) 60 C/6 weeks) 60
C/6 weeks)
1 0 1328 418 910
2 0.4 1326 433 893
3 0.8 1348 637 711
4 1.3 1360 712 648
5 2 1345 818 527
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Referring to Table 1 above, the lowest soluble fluoride drop on a parts per
million (ppm)
basis (column furthest on the right) is demonstrated by Example 5 by having 2
wt% of Iota-
carrageenan having only a ppm drop value of 527. The lower the soluble
fluoride ion drop, the
more stable the formulation. Example 5 had the highest amount of Iota-
carrageenan between
the five examples and therefore demonstrated the best soluble fluoride ion
stability among the
five formulations. Control E (example 1) had the poorest soluble fluoride
stability at 910 ppm.
The increasing amount of Iota- carrageenan of examples 2, 3, and 4 (i.e., 0.4,
0.8, and 1.3 wt%,
respectively) demonstrated increasing soluble fluoride ion stability as
evidenced by soluble
fluoride ion drop ppm values of 893, 711, and 648 respectively. In sum, Table
1 suggests the
l0 more carrageenan, the more soluble fluoride ion stable the formulation.
Table 2 below demonstrates that Lambda-carrageenan is the best between the
three
carrageenans in demonstrating fluoride ion stability on an equal weight basis.
Examples 6-10, as
described by the formulations of Figure 1, are briefly summarized. Examples 6,
7, and 8 have
increasing weight percentages (wt%) of Iota-Carrageen at 1 wt%, 2 wt%, and 3
wt%,
respectively. Example 9 has Kappa-carrageenan type at 2 wt% and Example 10 at
Lambda-
carrageenan type at 2 wt%.
Table 2:
Carrageenan Soluble Soluble Fluoride
Soluble Fluoride
Example type Fluoride (ppm, Drop (ppm,
(%w/w) (ppm, Day 1) 60 C/6 weeks) 60 C/6 weeks)
6 Iota/ 1 1311 300 1011
7 Iota/2 1228 400 828
8 Iota/3 1148 400 748
9 Kappa/ 2 1347 300 1047
10 Lambda/ 2, 1271 600 671
Referring to Table 2 above, the lowest soluble fluoride drop on a ppm basis
(column furthest
10 on the right) is demonstrated by Example 10 by having 2 wt% of Lambda-
carrageenan having
only a ppm drop value of 671. Examples 7, 8, and 10 all have equal amounts (2
wt%) of each
respective carrageenan type. Lambda- carrageenan (example 10) is the most
effective for
soluble fluoride ion stability, while Kappa- carrageenan (example 9) is the
least effective at 1047.
Notably, the increasing amount of Iota- carrageenan of examples 6, 7, and 8
respectively, show
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increasing amount of soluble fluoride ion stability (evidenced by the lower
ppm drops of 1011,
828, and 749, respectively).
Table 3 below demonstrates that a carrageenan containing dentifrice
formulation is better at
fluoride ion stability than two control formulations. Examples 11, 12, and 13,
as described by the
formulations of Figure 1, are briefly summarized. Example 11 contains Iota-
carrageenan at 1.4
wt%. Control A (Example 12) and Control B (Example 13) formulations do not
have any
carrageenan. Control A and Control B formulations both have slightly more
sodium
carboxymethyl cellulose (CMC) and thickening silica than Example 11, but
notably Control B
also has tetra sodium pyrophosphate (TSPP).
[0 Table 3:
Soluble Fluoride drop (ppm)
Example Formula difference: 60 C 4 weeks 60 C 6 weeks 30 C 52 weeks
11 Iota-carrageenan (1.4 wt%) 530 830 330
No Carrageenan
12 Tetrasodium Pyro- 888 988 688
phosphate
Tetrasodium Pyro-
13 phosphate 676 876 376
No Carragcenan
Referring to Table 3, the data takes into account possible fluoride ion
stability effects of
CMC, silica, and TSP. Given the lower soluble fluoride ion drop (ppm) of
carrageenan-
containing Example 11 at 4 weeks and 6 weeks at 60 C, as well as 30 C for
about one year,
[5 indicates that the carrageenan is providing improved fluoride ion
stability in the described
formulation as compared the control formulations. Example 12 does not contain
carrageenan,
but does contain tetrasodium pyrophosphate (TSPP).
Table 4 below demonstrates that a pH greater than 8.0 provides better fluoride
ion stability
in the dentifrice formulations described herein. Examples 11, 14, and 15, as
described by the
W formulations of Figure 1, are briefly summarized. Example 11 is at pH 9.4
and contains 1.414 wt%
of Iota-carrageenan, and also notably contains CMC and silica. Control C
(Example 14) and
Control D (Example 15) formulations are at a lower pH of 7.8 and 8.3,
respectively. Controls C
and D both also contain Iota-carrageenan at 2 wt% and 1.4 wt%, respectively.
The weight
percentages of silica, saccharine, and monofluorophosphate slightly of
Controls C and D differ
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from Example 11. Compared to example II, Control C and D also has a lower
level of calcium.
carbonate (25 wt% vs, 42 wt%) and higher level of water (65.32 wt% v. 48.96
wt%).
Table 4:
Soluble Soluble Fluoride Soluble Fluoride
Soluble
pH Fluoride (ppm, 60 C. Drop Fluoride drop
Ex. percentage
(ppm, Day I) 4 weeks) (ppm vs Day 1) (vs Day 1)
11. 9.4 1130 600 530 47%
14 7.8 850 340 510 60%
15 8.3 860 360 500 58%
Referring to Table 4, of the three lota-carrageenan containing samples.
Example 11 has the
best fluoride ion stability effects at 4 weeks at. 60 C having the highest
pH. of 9.4 by having a
soluble fluoride ion drop of 47% compared to Controls C and D which had much
higher drop
percentage at60% and 58% . respectively. Therefore, the data suggests that pH
8.3 is better than
7.8, and pH 9.4 is better than 8.3 when it comes to fluoride ion stability.
The dimensions and values disclosed herein are not to be understood as being
strictly
limited to the exact numerical values recited. Instead. unless otherwise
specified, each such
dimension is intended to mean both the recited value and a functionally
equivalent range
surrounding that value. For example, a dimension disclosed as "40 mm" is
intended to mean
"about 40 mm."
The citation of any document is not an admission that it is prior art with
respect to any
10 invention disclosed or claimed herein or that it alone, or in any
combination with any other
reference or references, teaches. suggests or discloses any such invention.
While particular embodiments of the present invention have been illustrated
and described,
it would be obvious to those skilled in the art that various other changes and
modifications can be
made without departing from the spirit and scope of the invention. It is
therefore intended to
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cover in the appended claims all such changes and modifications that are
within the scope of this
invention.
16
