Note: Descriptions are shown in the official language in which they were submitted.
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
1
REGIMEN FOR PROVIDING SMOOTH TOOTH FEEL
FIELD OF THE INVENTION
The present invention relates to a method of treating tooth surface with a
first composition
and then a second composition to provide a smooth tooth feel.
BACKGROUND OF THE INVENTION
Oral care products, such as toothpastes and mouth rinses, are routinely used
by consumers
as part of their oral care hygiene regimen. Oral care products are often
formulated to provide
both therapeutic and cosmetic hygiene benefits. Therapeutic benefits include
dental caries
prevention, gingivitis prevention, and hypersensitivity control. Cosmetic
benefits include control
of plaque and calculus formation, removal and prevention of tooth stain, tooth
whitening, breath
freshening, and overall improvements in mouth feel impression which can be
broadly
characterized as mouth feel aesthetics. Smooth tooth surface or slick tooth
feel is generally
considered as an important sign of thorough cleaning and effective delivery of
these benefits.
Abrasives, such as silica and calcium carbonate, are widely used in
toothpastes to remove
dental stains and polish the teeth, therefore smoothing the tooth surface and
providing a slick
tooth feel. However, the abrasion of abrasives on the tooth surface may lead
to abrasive damages
on dental enamel. Such abrasive damages include enamel loss (e.g., scratches,
micro-cracks, etc.)
and enamel thinning, which may roughen the tooth surface and make it easier
for undesirable
bacteria to deposit and invade into the tooth and consequently result in
enamel destruction. On
the other hand, a pellicle film to which the dental stains affix usually forms
on the surface of the
dental enamel within minutes after teeth are cleaned by selective binding of
glycoproteins from
saliva. The slick tooth feel may diminish soon after the adhesion of the thin
coating to the dental
enamel.
Therefore, there is a need to solve this problem. There is a need to smooth
the tooth surface
without abrasive damage to dental enamel. There is also a need to restore the
tooth surface
smoothness even after enamel loss or thinning. Finally, there is a need to
provide a long-lasting
smoothing effect on the tooth surface.
SUMMARY OF THE INVENTION
The present invention attempts to solve one or more of these problems. In one
aspect, the
present invention provides a method of treating a tooth surface, comprising
the steps:
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
2
(a) contacting the tooth surface with a first composition comprising a water-
insoluble
calcium phosphate, wherein the water-insoluble calcium phosphate has a calcium
to phosphorus
molar ratio from 1:1 to 10:1; and thereafter
(b) contacting the tooth surface with a second composition, wherein the second
composition
.. comprises an organophosphate having the formula:
0
II
R--(0-41(0¨Y)¨O¨P-0¨Z1
0¨Z2
wherein R is a hydrocarbyl comprising 4 to 22 carbon atoms; X and Y are each
independently an alkylene comprising 2 to 4 carbon atoms; a and b are each
independently an
integer selected from 0 to 20, wherein a+b is in the range from 0 to 20; Z1
and Z2 are each
independently selected from hydrogen, hydrocarbyl comprising 1 to 26 carbons
preferably
comprising one or more ether moieties, and a counter ion, provided that at
least one of Z1 and Z2
is hydrogen or a counter ion.
In another aspect, the present invention provides an oral care kit,
comprising:
(a) a first product containing a first composition, wherein the first
composition comprises
0.01% to 99% by weight of a water-insoluble calcium phosphate having a calcium
to phosphorus
molar ratio from 1:1 to 10:1;
(b) a second product containing a second composition, wherein the second
product is a
mouth rinse with a pH from 6 to 8 and a viscosity from 100 cps to 5000 cps,
and wherein the
second composition comprises 0.01% to 99% by weight of an organophosphate as
defined above;
and
(c) instructions instructing a user to first use the first product to contact
a tooth surface and
thereafter immediately use the second product to contact the tooth surface.
In a further aspect, the present invention provides an oral care product
comprising a first
container and a second container, wherein the first container contains a first
composition
comprising 0.01% to 99% by weight of a water-insoluble calcium phosphate which
has a calcium
to phosphorus molar ratio from 1:1 to 10:1, and the second container contains
a second
composition comprising 0.01% to 99% by weight of an organophosphate as defined
above; and
wherein the product optionally contains instructions instructing a user to
dispense the first
composition before the second composition is dispensed.
One aspect of the invention generally provides a sequential application system
of a calcium
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
3
source followed by a specific organophosphatc onto the tooth surface. Without
wishing to be
bound by theory, the first step of applying the calcium source is believed to
seal micro-cracks or
crevices in the tooth structure, and the second step of applying the specific
organophosphate is
believed to seal the calcium into the tooth structure. By this sequential
application system,
perceptible and meaningful improvements are delivered to the tooth surface, by
potentially
providing new crystal growth at sites of enamel loss or thinning, restoring
tooth surface
smoothness and/or building up a uniform protection layer to prolong the tooth
surface
smoothness.
These and other features, aspects, and advantages of the present invention
will become
evident to those skilled in the art from the detailed description which
follows.
BRIEF DESCRIPTION OF THE DRAWINGS
While the specification concludes with claims particularly defining and
distinctly claiming
the invention, it is believed that the invention will be better understood
from the following
description of the accompanying figures. In the accompanying figures,
Figs. 1(a) to 1(e) show property analysis of a tooth surface by Quartz Crystal
Microbalance
with Dissipation monitoring (QCM-D) when the tooth surface is treated
according to a specific
embodiment of the present invention.
Figs. 2(a) to 2(d) show Scanning Probe Microscopy (SPM) images of a tooth
surface before
treatment, after etching with citric acid, after a first step of treatment and
after a second step of
treatment, according to a specific embodiment of the present invention.
Figs. 3(a) to 3(d) show Scanning Probe Microscopy (SPM) images of a tooth
surface before
treatment, after etching with citric acid, after a first step of treatment and
after a second step of
treatment, according to a comparative embodiment.
Figs. 4(a) to 4(c) show Scanning Probe Microscopy (SPM) images of a tooth
surface before
treatment, after etching with citric acid, and after a one-step treatment,
according to another
comparative embodiment.
Fig. 5 shows panel test results about slick tooth feel over time for 3 hours
after treatment,
according to a specific embodiment of the present invention as well as after
treatment according
to comparative embodiments.
DETAILED DESCRIPTION OF THE INVENTION
The terms "oral composition" and "oral care composition" are used
interchangeably herein,
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
4
and refer to a product, which in the ordinary course of usage, is not
intentionally swallowed for
purposes of systemic administration of particular therapeutic agents, but is
rather retained in the
oral cavity for a time sufficient to contact dental surfaces and/or oral
tissues for purposes of topical
administration.
The term "dentifrice", as used herein, includes paste, gel, liquid, powder or
tablet formulations
for cleaning teeth with the aid of a toothbrush unless otherwise specified.
The dentifrice
composition may be a single phase composition or may be a combination of two
or more separate
dentifrice compositions.
The term "water-insoluble", as used herein, means having a low solubility in
water or being
incapable of being fully dissolved in water. Specifically, a water-insoluble
substance is intended
to mean a substance which has a solubility at 20 C of less than 1 g/l and in
particular of less than
1 mg/l.
The term "water-soluble", as used herein, means having a high solubility in
water or being
capable of being fully dissolved in water. Specifically, a water-soluble
substance is intended to
mean a substance which has a solubility at 20 C of no less than 1 g/1 and in
particular of no less
than 10 g/l.
The term "particle size", as used herein, refers to a volume based particle
size measured by
laser diffraction methods. Laser diffraction measures particle size
distributions by measuring the
angular variation in intensity of light scattered as a laser beam passes
through a dispersed
particulate sample. Large particles scatter light at small angles relative to
the laser beam and
small particles scatter light at large angles. The angular scattering
intensity data is then analyzed
to calculate the size of the particles responsible for creating the scattering
pattern, using the Mie
theory of light scattering. The particle size is reported as a volume
equivalent sphere diameter.
The term "mean particle size" and "average particle size" are used
interchangeably herein, and
refer to an average value of particle size distribution calculated based on
the logarithmic scale.
The terms "hydrocarbyl", "hydrocarbyl substituent" and "hydrocarbyl group" are
used
interchangeably herein, and refer to a univalent radical having a carbon atom
directly attached to
the remainder of the molecule and having predominantly hydrocarbon character.
Such a univalent
radical can be classified as an aliphatic group, cyclic group, or combination
of aliphatic and cyclic
groups (e.g., alkaryl and aralkyl groups). The term "aliphatic group" means a
saturated or
unsaturated linear or branched hydrocarbon group. This term is used to
encompass alkyl, alkenyl,
and alkynyl groups, for example. The term "alkyl group" means a saturated
linear or branched
hydrocarbon group including, for example, methyl, ethyl, isopropyl, t-butyl,
heptyl, dodecyl,
AA898F 5
octadecyl, amyl, 2-ethylhexyl, and thc like. The term "alkenyl group" means an
unsaturated, linear
or branched hydrocarbon group with one or more carbon-carbon double bonds,
such as a vinyl
group. The term "alkynyl group" means an unsaturated, linear or branched
hydrocarbon group
with one or more carbon-carbon triple bonds. The term "cyclic group" means a
closed ring
hydrocarbon group that is classified as an alicyclic group, aromatic group, or
heterocyclic group.
The term "alicyclic group" means a cyclic hydrocarbon group having properties
resembling those
of aliphatic groups. The term "aromatic group" or "aryl group" means a mono-
or polynuclear
aromatic hydrocarbon group.
The term "viscosity", as mentioned herein, is measured using Brookfield
viscometers with
cone and plate attachment. For viscosities in the range of 0-16000cps, the
Brookfield DV-II
TM
viscometer with SO2 plate is used. A 500m1 sample of the composition is
equilibrated at 25 C
for three minutes before the readings are taken at 2.5 rpm. For viscosities
greater than 16000cps
and up to 33000cps, the Brookfield DV-I viscometer with SO2 plate is used. A
500m1 sample of
the composition is equilibrated for 1 minute at 25 C before the readings are
taken at 0.3 rpm.
The term "tooth" or its plural form "teeth", as used herein, refers to natural
tooth as well as
artificial tooth or dental prosthesis.
Active and other ingredients useful herein may be categorized or described by
their
cosmetic and/or therapeutic benefit or their postulated mode of action or
function. However, it is
to be understood that the active and other ingredients useful herein can, in
some instances,
provide more than one cosmetic and/or therapeutic benefit or function or
operate via more than
one mode of action. Therefore, classifications herein are made for the sake of
convenience and
are not intended to limit an ingredient to the particularly stated application
or applications listed.
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
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.
CA 2929053 2017-10-05
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
6
Sequential Application System
In accordance with the present invention, a sequential application system is
provided to treat
the tooth surface.
In the first step (a), the tooth surface is contacted with a first composition
comprising a
water-insoluble calcium phosphate, wherein the water-insoluble calcium
phosphate has a calcium
to phosphorus molar ratio from 1:1 to 10:1. The water-insoluble calcium
phosphate particles can
deposit into micro-cracks and crevices, providing a source of calcium and
phosphate ions for
remineralization of the dental enamel.
In the second step (b), the tooth surface is further contacted with a second
composition
comprising the organophosphate as defined hereinabove. The organophosphate can
form a
protection layer on the tooth surface so as to seal the calcium and phosphate
ions into the tooth
structure.
In a specific embodiment, contacting step (b) is initiated within 30 minutes,
within 15
minutes, within 5 minutes, or immediately after the conclusion of contacting
step (a). It is
preferred that there is no intervening dental treatment step between step (a)
and step (b).
The contacting steps can be achieved by any oral care hygiene regimen, for
example,
selected from the group consisting of brushing, flossing, rinsing, plastering,
attaching, and
combinations thereof. Accordingly, the first composition and the second
composition can be in
various forms to facilitate the oral care hygiene regimen. Such forms include
but are not limited to
toothpaste, tooth powder, tooth gel, dental floss, mouth rinse, chewable
tablet, chewing gum, or
strip or film for direct application or attachment to the tooth surface. In a
specific embodiment, the
first composition is a toothpaste composition and the second composition is a
mouth rinse. In
another specific embodiment, the first composition and the second composition
are each
independently a mouth rinse.
The contacting duration depends on the specific regimen and the specific
composition form.
For example, brushing with a toothpaste may be conducted from 1 to 5 minutes,
rinsing with a
mouth rinse may be conducted from 5 seconds to 2 minutes, and plastering with
a strip or film
may be conducted from 5 minutes to 60 minutes, preferably from 20 minutes to
40 minutes.
In a specific embodiment, contacting steps (a) and (b) each independently has
a contacting
duration from 5 seconds to 5 minutes; and contacting step (b) is initiated
immediately after the
conclusion of contacting step (a).
In a specific embodiment, contacting step (a) is achieved by brushing the
tooth surface with
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
7
a toothpaste comprising the first composition, and then contacting step (b) is
immediately
achieved by rinsing the tooth surface with a mouth rinse comprising the second
composition.
In another specific embodiment, contacting step (a) is achieved by rinsing the
tooth surface
with a first mouth rinse comprising the first composition, and then contacting
step (b) is
immediately achieved by rinsing the tooth surface with a second mouth rinse
comprising the
second composition.
The First Composition
Tooth surfaces are constantly experiencing a loss and gain of minerals. This
process is
partially kept in balance by the chemical composition of saliva and the extra-
cellular fluid.
Disruption of the tooth surface integrity can occur by acidic food and
beverages, bacterial
challenge and erosion by exaggerated tooth brushing or grinding of the teeth.
These processes
are accompanied by a demineralization of the exposed tooth surfaces leading to
surface
roughness. Therefore, according to the present invention, the first
composition provides a source
of calcium and phosphate ions for remineralization of the dental enamel by
depositing into
micro-cracks and crevices in the tooth structure or on the tooth surface.
In a specific embodiment, the first composition comprises a water-insoluble
calcium
phosphate, wherein the water-insoluble calcium phosphate has a calcium to
phosphorus molar
ratio from 1:1 to 10:1.
Calcium phosphate is the main mineral found in teeth. Tooth enamel is composed
of almost
ninety percent of hydroxyapatite which is a calcium phosphate mineral known as
bone mineral.
The water-insoluble calcium phosphate as used in the present invention can
release and deliver
small amounts of calcium and phosphate ions under physiological conditions for
promoting
remineralization of the tooth enamel.
It has also been found that a specific calcium to phosphorus molar ratio range
is important
for tooth health and remineralization of the tooth enamel. A ratio of calcium
to phosphorus that
is too high may not be effective in inhibiting caries of the crowns and/or
tartar on teeth, while
one that is too low may not be effective in inhibiting caries near the gum
and/or may increase
inflammatory tendencies such as pyorrhea and gingivitis. In a specific
embodiment, the water-
insoluble calcium phosphate has a calcium to phosphorus molar ratio from 1:1
to 5:1, or from 1:1
to 3:1, or from 1.5:1 to 2.5:1, or from 1.3:1 to 2:1.
Suitable water-insoluble calcium phosphates useful in the present invention
include, but are
not limited to, apatite, calcium halide phosphate, dicalcium phosphate,
tricalcium phosphate,
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
8
octacalcium phosphate, and mixtures thereof. In an embodiment, the apatite is
selected from the
group consisting of hydroxyapatitc (Calo(PO4)6(OH)7), fluorapatite
(Caio(1)04)6F7), chlorapatite
(Calo(PO4)6C17), bromapatite (Calo(PO4)6B0 and mixtures thereof.
The water-insoluble calcium phosphate can be in any solid form, for example,
substantially
spherical particles, agglomerates of smaller particles, rod-like particles,
needle-like particles,
fibroid particles or mixtures thereof.
The water-insoluble calcium phosphate can be of any size which can deposit
onto the tooth
surface without impairing the spirit of the present invention. In a specific
embodiment, the
water-insoluble calcium phosphate has a particle size from 0.01, 0.5, 1, 2, or
4 to 5, 8, 10, 15 or
20 microns.
According to the present invention, the geometry and size of the water-
insoluble calcium
phosphate particles can be optimized so that the various micro-cracks or
crevices on the tooth
surface are taken into account.
The water-insoluble calcium phosphate is present in an amount from 0.01%,
0.05%, 0.1%,
0.5%, 1%, or 2% to 3%, 5%, 10%, 20%, 50%, or 99%, by weight, of the first
composition. In a
specific embodiment, the first composition comprises 0.1% to 20%, by weight,
of apatite. In a
further specific embodiment, the first composition comprises 1% to 5%, by
weight, of
hydroxyapatite. The amount of the water-insoluble calcium phosphate can be
adjusted to provide
the desired technical and sensorial benefits while mitigating any side
effects. In some medical or
clinical cases when the side effects do not matter much, the amount of the
water-insoluble
calcium phosphate can be up to 99%, by weight, of the first composition.
The pH of the first composition can be in the range from 6, 7, or 8 to 9, 10,
or 11. The pH
can be achieved through a proper balancing of the calcium phosphate sources or
by addition of an
alkaline or acidic agent. Without wishing to be bound by theory, a relatively
basic pH is
preferred because it is believed to stabilize the water-insoluble calcium
phosphate from being
dissolved.
The Second Composition
According to the present invention, the second composition comprises a
specific
organophosphate compound. The organophosphate compound has a strong affinity
for enamel
surfaces, like teeth, and has a sufficient surface binding propensity to
desorb pellicle proteins and
remain affixed to enamel surfaces. Without wishing to be bound by any theory,
it is believed that,
when applied according to the present invention, the organophosphate compound
adheres to the
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
9
teeth, with the phosphate groups binding the calcium in teeth and thus
preventing loss of calcium
from dissolution into acidic saliva. The organophosphatc may also deposit a
protective surface
coating that prevents teeth from coming into direct contact with erosive acids
or other harmful
substances.
In particular, the second composition comprises an organophosphate having the
formula:
0
II
R--(0-41(0¨Y)¨O¨P-0¨Z1
0¨Z2
wherein R is a hydrocarbyl comprising 4 to 22 carbon atoms; X and Y are each
independently an alkylene comprising 2 to 4 carbon atoms; a and b are each
independently an
integer selected from 0 to 20, and a+b is in the range from 0 to 20; Z1 and Z2
are each
independently selected from hydrogen, hydrocarbyl comprising 1 to 26 carbons
preferably
comprising one or more ether moieties, and a counter ion, provided that at
least one of Z1 and Z2
is hydrogen or a counter ion.
Examples of hydrocarbyl groups useful herein include, but are not limited to:
(1) hydrocarbon
substituents, that is, aliphatic (e.g., alkyl or alkenyl), alicyclic (e.g.,
cycloalkyl, cycloalkenyl)
substituents, and aromatic-, aliphatic-, and alicyclic-substituted aromatic
substituents, as well as
cyclic substituents wherein the ring is completed through another portion of
the molecule (e.g., two
substituents together form an alicyclic radical) and equivalents thereof; (2)
substituted hydrocarbon
substituents, that is, substituents containing non-hydrocarbon groups which,
in the context of the
description herein, do not alter the predominantly hydrocarbon substituent
(e.g., halo (especially
chloro and fluoro), hydroxy, alkoxy, mercapto, alkylmercapto, nitro, nitroso,
and sulfoxy) and
equivalents thereof; (3) hetero-substituents, that is, substituents which,
while having a
predominantly hydrocarbon character, in the context of this description,
contain other than carbon
in a ring or chain otherwise composed of carbon atoms and equivalents thereof
Hetero-atoms
include sulfur, oxygen, nitrogen, and encompass substituents such as pyridyl,
furyl, thienyl and
.. imidazolyl. In a specific embodiment, no more than two, preferably no more
than one, non-
hydrocarbon substituent is present for every ten carbon atoms in the
hydrocarbyl group. In a
further specific embodiment, there is no non-hydrocarbon substituent in the
hydrocarbyl group.
The presence of the hydrocarbyl group is believed to impart to the compound a
degree of
hydrophobicity, so that the organophosphate can effectively form a hydrophobic
layer on the tooth
surface. Such a hydrophobic layer can protect the enamel from erosive acidic
challenges and stain
AA898F 10
deposition, and provide good smooth feeling for a prolonged time.
Some examples of the organophosphate include, but are not limited to, alkyl
phosphates and
alkyl (poly)alkoxy phosphates, such as lauryl phosphate (tradenames MA1r230K
and MAPM 230T
TM
commercially available from Croda, Snaith, UK); PPG5 ceteareth-10 phosphate
(Crodaphos SG
commercially available from Croda, Snaith, UK); laureth-1 phosphate
(tradenames MAPM L210
commercially available from Rhodia, La Dffense, France, Phosten HLP-1
commercially
available from Nikkol Chemical, Tokyo, Japan, or SunmaerL commercially
available from
M
Sunjin Chemical, Korea); laureth-3 phosphate (tradenames MAP L130 commercially
available
from Rhodia, La Defense, France, Foamphoa,-3 commercially available from Alzo,
NJ, U.S., or
Emphiphos DF 1326 commercially available from Huntsman Chemical, Texas, U.S.);
laureth-9
phosphate (tradename Foamphos commercially available from Alzo, NJ, U.S.);
trilaureth-4
TN,
phosphate (tradenames Hostaphat KL 340D commercially available from Clariant,
Muttcnz,
Switzerland, or TLP-4 commercially available from Nikkol Chemical, Tokyo,
Japan); C12-18
PEG 9 phosphate (tradename CrafolTMAP261 commercially available from Cognis,
Ludwigshafen,
Germany); sodium dilaureth-10 phosphate (tradename DLP-10 commercially
available from
Nikkol Chemical, Tokyo, Japan).
Particularly preferred organophosphates are those containing alkoxy groups,
especially
repeating alkoxy groups, (0-X)a(0-Y)(, in particular those containing 1 or
more ethoxy, propoxy,
isopropoxy, butoxy groups or combinations thereof The presence of the alkoxy
group is believed
to increase the solubility of the compound and balance the amphiphilicity of
the compound, so that
the hydrophilic phosphate head can "stick" to the tooth surface (given its
charge) while the
hydrophobic hydrocarbyl tail is extended to a long carbon chain. On the other
hand, the presence
of the alkoxy group can help diffusing substances away from the tooth surface.
Additional suitable organophosphates may include alkyl mono glyceride
phosphate, alkyl
sorbitan phosphate, alkyl methyl glucoside phosphate, alkyl sucrose
phosphates, dextran
phosphate, polyglucoside phosphate, alkyl polyglucoside phosphate,
polyglyceryl phosphate,
alkyl polyglyceryl phosphate, polyether phosphates and alkoxylated polyol
phosphates. Some
specific examples may include polyethylene glycol (PEG) phosphate,
polypropylene glycol (PPG)
phosphate, alkyl PPG phosphate, PEG/PPG phosphate, alkyl PEG/PPG phosphate,
PEG/PPG/PEG phosphate, dipropylene glycol phosphate, PEG glyccryl phosphate,
polybutylene
glycol (PBG) phosphate, PEG cyclodextrin phosphate, PEG sorbitan phosphate,
PEG alkyl
sorbitan phosphate, PEG methyl glucoside phosphate, and combinations thereof.
The organophosphate may provide desired surface conditioning effects
including: I)
CA 2929053 2017-10-05
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
11
effective desorption of undesirably adsorbed pellicle proteins, in particular
those associated with
tooth stain binding, calculus development and attraction of undesirable
microbial species, and 2)
maintaining surface conditioning effects and control of pellicle film
formation for extended
periods following product use. The present compositions provide a protective
surface coating by
binding calcium minerals within teeth (e.g., hydroxyapatite). The protective
surface coating
provides improved tooth surface characteristics by modifying surface
hydrophilic and
hydrophobic properties and improving resistance to dietary acid attack.
The amount of the organophosphate in the second composition is an effective
amount to
provide the protection layer with good smooth feeling for some desired time.
Preferably, the
protection will last for at least an hour after use of the composition. The
organophosphate can be
present in an amount effective to provide an increase of at least 10 degrees
in water contact angle
on the surface, with the hydrophobic character being maintained for a period
of at least 5 minutes.
In a specific embodiment, the organophosphate is present in an amount ranging
from 0.01%,
0.02%, 0.03%, 0.05%, 0.07%, or 0.1% to 0.5%, 1%, 5%, 10%, 50%, or 99%, by
weight, of the
second composition. The amount of the organophosphate can be adjusted to
provide the desired
technical and sensorial benefits while mitigating any side effects which the
organophosphate
compound may have, for example, an undesirable bitter or soapy taste. In some
medical or
clinical cases when the undesirable bitter or soapy taste is not a big
consideration, the amount of
the organophosphate can be up to 99%, by weight, of the second composition.
In a specific embodiment, the organophosphate is defined by: R is an alkyl
comprising 8 to
16 carbon atoms; a+b is from 1 to 10; and Z1 and Z2 are each independently
selected from the
group consisting of hydrogen and an alkali metal counter ion. Preferably, at
least one of Z1 and
Z2 is an alkali metal counter ion selected from the group consisting of sodium
ion and potassium
ion; and wherein the second composition comprises 0.01% to 10 %, by weight, of
the
organophosphate.
Specifically, the organophosphate can be selected from the group consisting of
sodium
laureth-1 phosphate, sodium laureth-2 phosphate, sodium laureth-3 phosphate,
sodium laureth-4
phosphate, potassium laureth-1 phosphate, sodium laureth-9 phosphate, sodium
myreth-2
phosphate, sodium pareth-1 phosphate and mixtures thereof.
In a specific embodiment, the second composition comprises 0.01% or 0.05% to
5% or 10%,
by weight, of sodium laureth-1 phosphate.
The pH of the second composition can be in the range from 5, 6, or 6.5 to 7.5,
8 or 10. The
pH of the second composition should not be too low since there is a
possibility of the
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
12
organophosphate hydrolyzing in a strong acidic environment.
Optional Components
The first composition and the second composition of the present invention can
each
independently contain a variety of optional conventional components useful in
oral compositions
to increase the benefits mentioned herein or provide additional benefits. Such
optional
components include, but are not limited to, a fluoride ion source, a
thickening agent, a humectant,
a surfactant, an antibacterial agent, a colorant, a flavorant, and some other
conventional
components.
A fluoride ion source, also called a water-soluble fluoride source, capable of
providing free
fluoride ions, can help accelerating remineralization by increasing local
supersaturation with
respect to fluoridated calcium phosphate deposition. Fluoride uptake or
fluoridation refers to the
acquisition of fluoride into tooth substrates resulting from topical
treatments with fluoride agents.
Teeth with increased remineralization and fluoride uptake exhibit superior
resistance to acid
demineralization and therefore help prolong the smoothing effect on the tooth
surface. The
water-soluble fluoride source can be selected from the group consisting of
sodium fluoride,
stannous fluoride, sodium monofluorophosphate, amine fluoride, and mixtures
thereof. In a
specific embodiment, the second composition comprises a water-soluble fluoride
source capable
of providing from 50 ppm, 500 ppm, 1000 ppm, or 1500 ppm to 2000 ppm, 2500
ppm, 3000 ppm,
or 3500 ppm of free fluoride ions. In a further specific embodiment, the
second composition
comprises 0.005%, 0.01%, or 0.02% to 0.1%, 1%, or 5%, by weight, of sodium
fluoride. In an
even further specific embodiment, the first composition comprises 1% to 5%, by
weight, of
hydroxyapatite, and the second composition comprises 0.05% to 5%, by weight,
of sodium
laureth-1 phosphate and 0.01% to 1%, by weight, of sodium fluoride.
Thickening agents, also called thickeners, are generally used to increase the
viscosity of a
solution or liquid/solid mixture. According to the present invention,
thickening agents can be
incorporated to provide a consumer desirable consistency and tooth coating
ability by adjusting
the viscosity of the composition. The oral care composition of the present
invention can have a
viscosity ranging from 10cps, 50cps, 100cps, 500cps, 800cps, 1200cps, or
2000cps to 3000cps,
5000cps, 8000cps, 12000cps, 20000cps, 30000cps, or 45000cps, depending on the
delivery form
of the composition. In a specific embodiment, the first composition has a
viscosity of 2000cps to
8000cps. In another specific embodiment, the second composition has a
viscosity of 1200cps to
3000cps. Thicker composition tends to provide longer lasting benefits on the
tooth surface.
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
13
Thickening agents may also improve the suspension of insoluble ingredients to
provide a stable
and uniform composition. This is especially advantageous when the first
composition
comprising the water-insoluble calcium phosphate is a mouth rinse. Preferred
thickening agents
are selected from the group consisting of carboxyvinyl polymers, carrageenan,
xanthan gum,
cellulosic polymers, hydroxyethyl cellulose, carboxymethyl cellulose, ammonium
acryloyldimethyltaurate/vinylprrolidone copolymer, polyethylene oxide,
acrylates/C10-30 alkyl
acrylate crosspolymer, polyacrylic acid, cross-linked polyacrylic acid,
polycarbophil, alginate,
clay, glucose, pectin, gelatin, and combinations thereof Colloidal magnesium
aluminum silicate
or finely divided silica can also be used as part of the thickening agent to
further improve texture.
The thickening agent can be present in an amount from 0.01%, 0.1%, 0.2%, 0.3%,
or 0.4% to 2%,
5%, 8%, 10%, or 20%, by weight, of the first composition or the second
composition.
Humectants such as polyethylene glycols can also been used to modify viscosity
and to
provide a smooth feel to dentifrice compositions. Polyethylene glycols are
available in a large
range of average molecular weights and have different properties depending
upon their average
molecular weights. The humectant serves to keep the oral composition,
especially a toothpaste
composition, from hardening upon exposure to air and give a moist feel to the
mouth. Certain
humectants can also impart a desirable sweet flavor to oral compositions such
as mouth rinse and
toothpaste. Suitable humectants for use in the present invention include
edible polyhydric
alcohols such as glycerin, sorbitol, xylitol, butylene glycol, polyethylene
glycol, propylene glycol,
and mixtures thereof The humectant is optionally present in an amount of 1%,
2%, 5%, or 8% to
15%, 25%, 50%, or 70%, by weight, of the first composition or the second
composition.
Surfactants are useful, for example, to make other components of the oral care
composition
more compatible with one another. This provides enhanced stability, helps in
cleaning the dental
surface through detergency, and provides foam upon agitation, e.g., during
brushing with a
dentifrice composition of the invention. Any orally acceptable surfactant,
most of which are
anionic, nonionic or amphoteric, can be used. Suitable anionic surfactants
include without
limitation water-soluble salts of C8-20 alkyl sulfates, sulfonated
monoglycerides of C8-20 fatty
acids, sarcosinates, taurates and the like. Illustrative examples of these and
other classes include
sodium lauryl sulfate, sodium coconut monoglyceride sulfonate, sodium lauryl
sarcosinate,
sodium lauryl isoethionate, sodium laureth carboxylate and sodium dodecyl
benzenesulfonate.
Suitable nonionic surfactants include without limitation poloxamers,
polyoxyethylene sorbitan
esters, fatty alcohol ethoxylates, alkylphenol ethoxylates, tertiary amine
oxides, tertiary
phosphine oxides, dialkyl sulfoxides and the like. Suitable amphoteric
surfactants include
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
14
without limitation derivatives of C8-20 aliphatic secondary and tertiary
amines having an anionic
group such as carboxylate, sulfate, sulfonate, phosphate or phosphonatc. A
suitable example is
cocoamidopropyl betaine. The surfactant is optionally present in an amount of
0.01%, 0.05%, or
0.1% to 2%, 5%, or 10%, by weight, of the first composition or the second
composition.
Antibacterial agents useful in the present invention include but are not
limited to water
insoluble non-cationic antibacterial agents and water soluble antibacterial
agents such as
quaternary ammonium salts and bis-biquanide salts. Triclosan monophosphate is
an additional
water soluble antibacterial agent. In some preferred embodiments, the
antibacterial agent is
selected from the group consisting of cetylpyridinium halide, domiphen halide,
a stannous ion
source, a zinc ion source, a copper ion source, and mixtures thereof. These
antibacterial agents
may be present at levels of from 0.01%, 0.05%, 0.1%, or 0.2% to 0.5%, 1.0%,
1.2% or 1.5%, by
weight, of the first composition or the second composition.
Colorants herein include pigments, dyes, lakes and agents imparting a
particular luster or
reflectivity such as pearling agents. A colorant can serve a number of
functions, including for
example to provide a white or light-colored coating on a dental surface, to
act as an indicator of
locations on a dental surface that have been effectively contacted by the
composition, and/or to
modify appearance, in particular color and/or opacity, of the composition to
enhance
attractiveness to the user. Any orally acceptable colorant can be used,
including but not limited
to talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate,
magnesium
aluminum silicate, silica, titanium dioxide, zinc oxide, red, yellow, brown
and black iron oxides,
ferric ammonium ferrocyanide, manganese violet, ultramarine, titaniated mica,
bismuth
oxychloride and the like.
Flavorants are useful for example to enhance taste of the composition. Any
orally
acceptable natural or synthetic flavorant can be used, including but not
limited to vanillin, sage,
marjoram, parsley oil, spearmint oil, cinnamon oil, oil of wintergreen
(methylsalicylate),
peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, citrus oils,
fruit oils and essences
including those derived from lemon, orange, lime, grapefruit, apricot, banana,
grape, apple,
strawberry, cherry, pineapple, etc., bean- and nut-derived flavors such as
coffee, cocoa, cola,
peanut, almond, etc., adsorbed and encapsulated flavorants and the like. Also
encompassed
within flavorants herein are ingredients that provide fragrance and/or other
sensory effect in the
mouth, including cooling or warming effects. Such ingredients illustratively
include menthol,
menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol,
anethole, eugenol, cassia,
oxanone, a-irisone, propenyl guaiethol, thymol, linalool, benzaldehyde,
cinnamaldehyde, N-
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
ethyl-p-mcnthan-3-c arboxamine, N,2,3-trimethy1-2-isopropylbutanamide,
3 -(1-menthoxy)-
propane-1,2-diol, cinnamaldchyde glycerol acctal (CGA), menthone glycerol
acctal (MGA) and
the like.
5 Oral Care Kit and Product
The present invention also provides any form of kit and product comprising the
first
composition and the second composition as discussed above.
In some embodiments, the oral care kit comprises:
(a) a first product containing a first composition, wherein the first
composition comprises
10 0.01% to 99%, by weight, of a water-insoluble calcium phosphate having a
calcium to
phosphorus molar ratio from 1:1 to 10:1;
(b) a second product containing a second composition, wherein the second
product is a
mouth rinse with a pH from 6 to 8 and a viscosity from 100 cps to 5000 cps,
and wherein the
second composition comprises 0.01% to 99%, by weight, of an organophosphate as
defined
15 above; and
(c) instructions instructing a user to first use the first product to contact
a tooth surface and
thereafter immediately use the second product to contact the tooth surface.
In some embodiments, the kit further includes an applicator to apply the first
and/or second
compositions to the tooth surface, for example, a syringe-type applicator for
depositing a
composition on the tooth surface or an applicator in the shape of a
semicircular trough for use in
applying composition to the tooth surface. The kit may also optionally include
instructions on
the use of an applicator in applying the composition to a tooth surface.
In a specific embodiment, the first product and the second product can be
physically
separated, each independently as any suitable form, for example, as a liquid
form or a dry powder.
When the composition provided is a dry powder, the composition may be
reconstituted by the
addition of a suitable solvent, which may also be included in the kit. In
embodiments where a
liquid form is provided, the composition may be concentrated or ready to use.
In a specific embodiment, the first product and the second product are each
independently a
mouth rinse.
In some embodiments, the present invention intends to provide a single oral
care product
comprising a first container and a second container, wherein the first
container contains a first
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
16
composition comprising 0.01% to 99%, by weight, of a water-insoluble calcium
phosphate which
has a calcium to phosphorus molar ratio from 1:1 to 10:1, and the second
container contains a
second composition comprising 0.01% to 99%, by weight, of an organophosphate
as defined
above. The product may optionally contain instructions instructing a user to
dispense the first
composition before the second composition is dispensed.
In a specific embodiment, the single oral care product further comprises
instructions
instructing a user to first dispense the first composition from the first
container to contact a tooth
surface and thereafter dispense the second composition from the second
container to contact the
tooth surface for every use.
In another specific embodiment, the single oral care product further comprises
a pump
which pumps the first composition from the first container upon a first
actuation and pumps the
second composition from the second container upon a second actuation for every
treatment
regimen use.
EXAMPLES
The following examples further describe and demonstrate embodiments within the
scope of
the present invention. These examples are given solely for the purpose of
illustration and are not
meant to be construed as limitations of the present invention, as many
variations thereof are
possible without departing from the spirit and scope of the present invention.
The first composition
Table 1 shows examples of the first composition according to the present
invention in the
form of mouth rinses. The preparation process is as follows: add glycerin and
polymers to a first
mixing vessel, mixing until well dispersed to get Premix 1; add water (10% of
the total amount),
flavors & sensates, hydroxyapatitc, sweeteners, liquid preservatives,
surfactants, and colorants &
aesthetics to a second mixing vessel, mixing until well dispersed and
homogenous to get Premix
2; add water (90% of the total amount), solid preservatives, and thickening
agents to a main
mixing tank, mixing until homogenous to get a main mix; add Premix 1 to the
main mix, mixing
until well dispersed; add 25% of the total sodium hydroxide (if applicable) to
the main mix,
mixing until homogenous; add Premix 2 to the main mix, mixing until well
dispersed and
homogenous; and add the rest of the sodium hydroxide until the pH is 7.
AA898F 17
Table 1
Ingredients Al A2 A3 A4 AS A6 A7 A8
Water 77.744
77.674 75.244 79.244 76.279 78.404 77.654 79.154
Glycerin 18.000
18.000 18.000 18.000 18.000 18.000 18.000 18.000
Methylparaben 0.020 0.020 0.020 0.020 0.020 0.020
0.020 0.020
Propylparaben 0.005 0.005 0.005 0.005 0.005 0.005
0.005 0.005
Benzyl Alcohol 1.000 0.900 1.000 1.000 0.900 0.900
0.900 0.900
Aristoflex'mAVC 0.500 - 0.500 0.500
Carbopol ETD2020 - 0.200 - 0.250 0.125 0.125
0.125
PolyoXrm WSR1105 - 0.200 - 1.000 0.500 0.500
0.500
Vitamin E Acetate - 0.070 - 0.070 0.070 0.070
0.070
Bio-Ger HTP1) 2.500 - 5.000 1.000
nanoXlivfm.Carc powder2) - 2.500 - 3.000 1.500 2.250
0.750
Sodium Saccharin 0.013 0.013 0.013 0.013 0.013 0.013
0.013 0.013
Sucralose 0.008 0.008 0.008 0.008 0.008 0.008
0.008 0.008
Peppennint'm 92 180 Blend 0.100 - 0.100 0.100
Starburstm Peppermint - 0.100 - 0.120 0.120 0.120
0.120
Sodium Hydroxide - 0.200 0.200 0.200 0.200
0.200
Titanium Dioxide 0.100 0.100 0.100 0.100 0.050 0.050
0.050 0.050
Poloxamerr" 407 0.010 0.010 0.010 0.010 0.010 0.010
0.010 0.010
Canduridm Silver Lustre - 0.075 0.075 0.075
0.075
Total 100 100 100 100 100 100 100
100
') Hydroxyapatite supplied by Bio-Rad, Hercules, CA, USA
2) Hydroxyapatite supplied by Fluidinova, Moreira da Maia, Portugal
As a mouth rinse, appropriate viscosity will suspend the hydroxyapatite
uniformly in the
composition and facilitate proper contact and retention of the composition on
the tooth surface.
The first compositions, Al to A8, have a viscosity of 2580 cps, 7690 cps, 5072
cps, 2600 cps,
29433 cps, 132 cps, 220 cps, and 116 cps, respectively.
Table 2 shows examples of the first composition according to the present
invention in the
form of toothpastes. The preparation process is as follows: add water,
humectants, part of flavor,
colorant, buffer and active to a main mixing tank of 35 C, mixing well and
ensuring all the
ingredients have dissolved or been well dispersed; add thickening agents and
sweetener into the
main mixing tank, mixing and homogenizing until well dispersed and
homogeneous; add
abrasives, mixing and homogenizing until well dispersed and homogeneous;
dcacrate; add
surfactant solution, rest part of flavor to the main mixing tank, mixing and
homogenizing until
CA 2929053 2017-10-05
AA898F 18
homogeneous; de-aerate; pump out and cool the batch to less than 40 C.
Table 2
Ingredients A9 A10 All Al2 A13
Sorbitol solution (70%) 22.169 40.370 40.500 -
23.000
Sodium fluoride 0.321 0.234 - - -
Water purified 45.000 33.096 22.950 -
44.170
Silica abrasive 15.000 12.500 17.000
17.000 15.000
Sodium Lauryl Sulfate (28%) 7.000 5.000 5.000 3.500
5.000
Sodium Carboxymethyl Cellulose 1.400 1.300 1.300 - 1.500
Carrageenan 0.700 0.700 0.600
Carbomer 956 0.400 - - - 0.500
Sodium saccharin 0.280 0.300 0.300 0.300
0.280
Xantlian gum 0.250 - - 0.250 0.250
Titanium dioxide 0.250 0.500 0.525 0.400
0.250
Flavor 0.900 1.000 0.900 1.000
1.000
Sodium hydroxide 32% 3.750 - - 3.750
Mica 0.280 _ - - 0.500
0.300
Ni ____________________________________________________________________
Bio-Gel' HTPi) 3.000 7.500 5.000
nanoXIMICare powder2) 5.000 10.000
Glycerin - - - 41.950 -
Sodium polyphosphate - - - 13.000 -
Sodium citrate - - 0.150 -
Sodium gluconate - 1.064 - - Zinc
citrate 0.955 0.375
Hydroxyethyl Cellulose 0.300 0.300 - -
Stannous chloride - 1.160 - -
Propylene glycol - - - 7.000 -
Polyethylene glycol - - - 7.000 -
Total 100 100 100 100 100
-1-) Hydroxyapatite supplied by Bio-Rad, Hercules, CA. USA
2, Hydroxyapatite supplied by Fluidinova, Morena da Maia, Portugal
The second composition
Table 3 shows examples of the second composition according to the present
invention in the
form of mouth rinses. The preparation process is the same as that for the
first compositions in
the form of mouth rinses, except that no hydroxyapatite is added in the Premix
2 and that sodium
fluoride and organophosphate are added along with water (90% of the total
amount), solid
preservatives, and thickening agents to get a main mix.
CA 2929053 2017-10-05
AA898F 19
Table 3
Ingredients B1 B2 B3 B4 B5 B6 B7
Water 80.014 80.144
79.914 79.729 79.364 79.794 79.704
Glycerin 18.000 18.000
18.000 18.000 18.000 18.000 18.000
Methylparaben 0.020
0.020 0.020 0.020 0.020 0.020 0.020
Propylparaben 0.005
0.005 0.005 0.005 0.005 0.005 0.005
Benzyl Alcohol 1.000 0.900 1.000 0.900 0.800
0.900 0.900
AristoflexTmAVC 0.400 - 0.500 -
Carbopol ETD2020 - 0.150 - 0.150 0.350 0.200
0. I 75
Polyox" WSK1105 - - 0.200 0.150 0.200
0.200
Vitamin E Acetate - 0.070 - 0.070 0.070 0.070
0.070
Sodium Fluoride - 0.050 - 0.020 0.050 0.050
0.020
MAP L213S3) 0.330 - 0.330 0.660 0.330
,
Foamphos L-941 - 0.330 0.330 - 0.330
Sodium Saccharin 0.013 0.013 0.013 0.013 0.013
0.013 0.013
Sucralose 0.008
0.008 0.008 0.008 0.008 0.008 0.008
Peppermint"192 180 Blend 0.100 - 0.100 0.100 0.100
0.100
StarburstTm Peppermint - - - - 0.100
Polar Mint Diluted - - - 0.120 0.120
Sodium Hydroxide - 0.200 - 0.200 0.200 0.200
0.200
Titanium Dioxide 0.100 0.100 0.100 0.050 0.100
0.100 0.050 ,
CanduriMm Silver Lustre - - 0.075 - 0.075
Timica" - Extra Bright - - - 0.100
PoloxamerTm 407 0.010 0.010 0.010 0.010 0.010
0.010 0.010
Total 100 100 100 100 100 100 100
3) Laurcth-1 phosphate supplied by Rhodia, pre-neutralized
4)Latireth-9 phosphate supplied by Alzo, neutralized with NaOH
The second compositions, B3 to B7, have a viscosity of 3072 cps, 1376 cps,
216.5 cps, 1408
cps, and 2616 cps, respectively. B1 and B2 arc not measured.
Table 4 shows examples of the second composition according to the present
invention in the
form of nonabrasive tooth gels.
Preparation process is as follows: add mineral
oil/petrolatum/Versagel, humectants, part of flavor, and colorant to a main
mixing tank of 35 C,
mixing well and ensuring all the ingredients have dissolved or been well
dispersed; add
organophosphate and sweetener into the main mixing tank, mixing and
homogenizing until well
dispersed and homogeneous; deaerate; add surfactant solution, rest part of
flavor to the main
mixing tank, mixing and homogenizing until homogeneous; deaerate; pump out and
cool the
CA 2929053 2017-10-05
AA898F 20
batch to less than 40 C.
Table 4
Ingredients B8 B9 B10 Bll B12
MAP L-1305) 13.330 - - - -
Foamphos TM L-395 8.000 - - -
TM
MAP 230K '7) - 10.000 - -
DLP-108) - - - 5.000 -
CrodaphosTM SG9) - - - - 2.000
Glycerin 20.000 13.000 22.000 35.000
Flavor 2.000 2.000 2.000 2.000 ,
1.000
Saccharin 0.500 0.500 0.500 0.500 2.000
Polyethylene oxide 2.000 2.000 2.000 2.000
Carbomdm 956 0.500 0.500 0.500 0.500 -
Mineral Oil - 55.000 , -
Petrolatum 61.670 64.000 63.000 - -
VcrsagelT" - - 95.000
Total 100 100 100 100 100
') Laurcth-3 phosphate supplied by Rhodia. neutralized with NaOH
8) Laureth-3 phosphate supplied by Alzo, neutralized with NaOH
7) Potassium C12/13 phosphate supplied by Croda
8) Sodium diLaureth-10 phosphate supplied by Nikko! Chemical
9) PPG5 Ceteareth-10 phosphate supplied by Croda, neutralized with NaOH
Sequential application system
One of the first compositions as shown in Tables 1 and 2 and one of the second
compositions as shown in Tables 3 and 4 can be combined into a sequential oral
application
treatment regimen. Examples of sequential compositions according to the
present invention are
shown in Table 5.
Table 5
Ex. 1 Ex. 2 Ex. 3 Ex. 4 Ex. 5 Ex. 6 Ex. 7
The first composition A2 A3 AS A7 A9 Al 1 Al2
The second composition B6 B8 BI B10 B3 B7 BI2
The compositions in the form of mouth rinses are applied to the tooth surface
by swishing
and gargling 20m1 of the mouth rinse in the mouth for 30 seconds and then
spitting out. In the
application where the subject composition is too viscous or too thick to be
swished or gargled in
CA 2929053 2017-10-05
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
21
the mouth, suitable applicators such as a swab can be used to apply (e.g.,
spread or daub) the
composition onto the tooth surface.
The compositions in the form of toothpastes are applied to the tooth surface
by brushing
with a toothbrush for 2 minutes.
The compositions in the form of tooth gels are applied to the tooth surface by
applying the
gels evenly into a mouth tray and putting the mouth tray onto the teeth for 10
minutes.
Efficacy measurement
Quartz Crystal Microbalance with Dissipation monitoring (QCM-D)
QCM-D is a very sensitive mass balance technique allowing simultaneous
measurement of
adsorption kinetics and viscoelastic properties of an adsorbing layer.
In QCM-D, a quartz crystal is excited to oscillate at its fundamental resonant
frequency by
the application of AC voltage across the crystal. A material adsorbed onto the
surface of the
crystal causes the resonant frequency to change, which is proportional to the
mass of the
adsorbed film.
The damping/dissipation of the crystal's oscillation by the film can be
measured, allowing
for the determination of the viscoelasticity of the film.
AD = Edissipationilt Estored
wherein D is the energy dissipated per oscillation divided by the total energy
stored in the crystal.
A large value for AD indicates that a soft, easily deformed material is
attached to the crystal.
A rigid material leads to a small AD.
Figs. 1(a) to 1(e) show the QCM-D data for a tooth surface treated with Ex. 1
of the present
invention.
Three steps, in sequential order, are followed to treat the test tooth
surface. The first step is
to rinse the tooth surface with deionized water. The second step is to rinse
the tooth surface with
the first composition, A2. The third step is to further rinse the tooth
surface with the second
composition, B6. The three columns in each of Figs. 1(a) to 1(e) represent the
QCM-D test
results after each step.
It can be seen from the QCM-D data that, before the treatment according to the
present
invention, no adsorbed layer is formed on the tooth surface. After treatment
with the first
composition, a layer displaying viscoelastic properties is adsorbed onto the
tooth surface. After
further treatment with the second composition, the adsorbed layer is
strengthened by increased
mass, density, and thickness.
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
22
Scanning Probe Microscopy (SPM)
Scanning probe microscopy is used to produce topographic images of a surface
with nano-
scale resolution. In this technique, the deflection of a microfabricated
cantilever spring is
monitored as it is raster scanned over the surface in question. Surface
roughness analysis allows
for quantitative measurements of topographical features as a function of
surface modification.
Figs. 2(a) to 2(d) show the changes of an enamel surface when it is treated
with Ex. 1 of the
present invention. Fig. 2(a) shows a rough enamel surface prior to treatment
(i.e., control). Fig.
2(b) shows that the enamel surface is further roughened by being etched with
citric acid. Fig. 2(c)
shows a slightly smoother enamel surface but with some insoluble components
(large particles)
deposited after the treatment with the first composition, A2. It is believed
that the hydroxyapatite
has been deposited onto the surface. Fig. 1(d) shows a smooth enamel surface
after subsequent
treatment with the second composition, B6.
In comparison, Figs. 3(a) to 3(d) show the enamel surface changes when treated
with the
same compositions in Ex. 1 of the present invention but in a different
sequence. In other words,
the comparative enamel surface is treated by the second composition, B6,
followed by the first
composition, A2. Fig. 3(a) shows a rough enamel surface prior to treatment
(i.e., control). Fig.
3(b) shows a similarly roughened enamel surface as Fig. 2(b) after being
etched with citric acid.
Fig. 3(c) shows a much smoother enamel surface than Fig. 2(c) after the
treatment with the
.. second composition, B6. However, after the two-step treatment of the second
composition, B6,
followed by the first composition, A2, Fig. 3(d) shows an enamel surface
rougher than that
shown in Fig. 2(d). In Fig. 3(d), the raised or depressed areas can be up to a
depth of 20nm,
compared to only 1 Onm in Fig. 2(d).
SPM images are also taken to show the enamel surface changes after a regular
treatment
with an Oral B Pro-Expert dentifrice (produced on March 18, 2011 in the US).
The Oral B
Pro-Expert dentifrice does not contain the first composition or the second
composition as defined
in the present invention. Fig. 4(a) shows a rough enamel surface prior to
treatment. Fig. 4(b)
shows a further roughened enamel surface by being etched with citric acid.
Fig. 4(c) shows the
enamel surface after the dentifrice treatment, which is almost as rough as the
etched enamel
surface. It can be seen that the dentifrice treatment hardly changes the
enamel surface
smoothness.
Overall, SPM data shows that the treatment according to the present invention
makes the
tooth surface much smoother.
CA 02929053 2016-04-28
WO 2015/074241 PCT/CN2013/087671
23
Sensory Panel Test (DPP)
A sensory panel test for slick tooth feeling is conducted by a Descriptive
Profile Panel (DPP)
comprised of 10 individuals who have been screened for above average sensory
acuity and ability
to describe sensations of slick tooth feeling. The panelists are trained on
oral care product
specific attributes via Spectrum(TM) methodology and have the unique ability
to evaluate oral
care products on an attribute by attribute basis without regard to personal
preference or bias. In
this test, panelists use the products as directed and evaluate the products
against their standard 3
hour clean mouth feel ballot (including a slick teeth measure) for 3 hours
after use. Panelists also
provide descriptive analysis and additional voluntary comments to call out any
other sensory
attributes. Each attribute is measured on a 0-30 scale with defined intervals
that are no longer
then 15 minutes. After the first hour, panelists drink 8 oz I 236.59 mL of a
carbonated beverage
(one of Coca-Cole', Caffeine Free Coca-Cole', Diet Coke, and Caffeine Free
Diet Coke) with
continued evaluation.
The products involved in this panel test include: the first composition (A2)
only; the second
composition (B6) only; a sequential application system of A2 followed by B6
according to Ex. 1
of the present invention; a sequential application system of B6 followed by
A2; and BioRepair
mouthwash (containing a hydroxyapatite variant, produced on June 11, 2011 in
British).
As shown in Fig. 5, the sequential application system of A2 followed by B6
according to the
present invention provides the best slick tooth feel over time. Although the
sequential
application system of B6 followed by A2 provides a comparable slick tooth feel
immediately
after the treatment, the values for slick tooth feel drop down quickly within
10 minutes after the
treatment. 20 minutes after the sequential treatment of B6 followed by A2, the
values for slick
tooth feel is much lower than those obtained by the sequential treatment
according to the present
invention, and even lower than those obtained by individual treatment with A2
or B6 only.
BioRepair0 mouthwash is a commercial product comprising zinc hydroxyapatite.
It can be
seen from Fig. 5 that both the immediate and the long-lasting slick tooth feel
evaluations are well
below those obtained by the sequential treatment according to the present
invention.
Unless otherwise indicated, all percentages, ratios, and proportions are
calculated based on
the weight of the total composition. All temperatures are in degrees Celsius (
C) unless
otherwise indicated. All measurements made are at 25 C, unless otherwise
designated. All
component or composition levels are in reference to the active level of that
component or
AA898F 24
composition, and are exclusive of impurities, for example, residual solvents
or by-products,
which may be present in commercially available sources.
It should be understood that every maximum numerical limitation given
throughout this
specification includes every lower numerical limitation, as if such lower
numerical limitations
were expressly written herein. Every minimum numerical limitation given
throughout this
specification will include every higher numerical limitation, as if such
higher numerical
limitations were expressly written herein. Every numerical range given
throughout this
specification will include every narrower numerical range that falls within
such broader
numerical range, as if such narrower numerical ranges were all expressly
written herein.
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
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.
Further, to the extent
that any meaning or definition of a term in this document conflicts with any
meaning or
definition of the same term in a document referenced herein, the meaning or
definition assigned
to that term in this document shall govern.
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
cover in the appended claims all such changes and modifications that are
within the scope of this
invention.
CA 2929053 2017-10-05
