Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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ORAL CAVITY CLEANING COMPOSITION, METHOD, AND APPARATUS
Claim of Priority and Cross-reference to related applications
[0001] This application is being filed on April 1, 2022, as an
International Patent
Application, and claims the benefit, to the extent appropriate, of and
priority to US Patent
Application Serial No. 17/225,049 filed April 7, 2021, and US Provisional
patent
application Serial No. 63/169,585 filed April 1, 2021, US Patent Application
Serial No.
17/225,049 is a OP of and claims priority to US Patent Application Serial No.
17/062,424 filed October 2, 2020, which claims priority to US Provisional
patent
application Serial No. 62/910,049, filed October 3, 2019, and US Provisional
patent
application Serial No. 62/913,565, filed October 10, 2019. US Provisional
patent
application Serial Nos. 17/225,049 and 17/062,424 and US patent application
Serial Nos.
63/169,585, 62/910,049, and 62/913,565 are incorporated herein by reference in
their
entireties.
[0002] The following additional patent application disclosures are
incorporated herein
by reference: Provisional Patent Application U.S. Serial No. 62/402,394, filed
September
30, 2016, including its appendix; Provisional Patent Application U.S. Serial
No.
62/563,975, filed September 27, 2017, including its appendices; Nonprovisional
Patent
Application U.S. Serial No. 15/718,325, filed September 28, 2017, which
published as
U520180094214A1 and issued as US10266793; PCT patent application
PCT/US17/53925, filed September 28, 2017, which published as W02018064284A1;
Provisional Patent Application U.S. Serial No. 62/652,079, filed April 3,
2018;
Provisional Patent Application U.S. Serial No. 62/692,082 filed June 29, 2018;
Provisional Patent Application U.S. Serial No. 62/822,432 filed March 22 2019;
Provisional Patent Application U.S. Serial No. USSN 62/828,134 filed April 2
2019;
PCT/US2019/025558, filed April 3, 2019; patent application U.S. Serial Number
16/461,536 filed May 16, 2019.
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Field of the invention
[0003] Embodiments of the invention include compositions and methods
suitable for use
in removing plaque biofilm from surfaces on and between teeth, and for
providing other
oral health benefits. The composition can be referred to as an oral hygiene
composition.
Background of the Invention
[0004] In the mouth, bacteria synthesize polysaccharides and proteins
and create a
scaffold matrix structure, in which they become embedded, thus creating what
is known
as oral biofilm, plaque-biofilm or dental plaque, which forms on teeth between
brushings.
Black, G.V., a researcher and a founder of modem dentistry (1836-1916),
characterized
dental plaque as a soft, mucinous, sticky, water insoluble material, which
forms on teeth.
Plaque remains soft and sticky for about a week or so, after which it
gradually
mineralizes, hardens (presumably as tartar) and becomes firmly affixed to the
tooth
surface and is normally referred to as tartar or calculus. Thereafter, it can
only be
removed with difficulty using instrumentation (Pader, M: Oral Hygiene Products
and
Practice (Marcel Dekker, Inc. NY), Chapter 4, Dental Plaque, pages 45-46).
[0005] Although one might think that the consistency of plaque biofilm
would make it
easy to remove completely from teeth, the physical removal of biofilm from
tooth
surfaces is actually not as easy as one might expect. Much of the difficulty
is associated
with getting access to the plaque, which builds up in difficult-to-reach
areas, for example
in fissures, at the gum-line where the tooth emerges from the gums and in
areas between
adjacent teeth (interproximal spaces). Another difficulty is in overcoming the
surface
tension forces between the water-insoluble biofilm and the tooth surface.
Additional
hindrance to removal, results from the binding of bacterial adhesins in
biofilm to the
lectins on the tooth surfaces and tooth pellicle. (Kolenbrander P & London J:
Adherence
Today, Here Tomorrow. Oral Bacterial Adherence. Journal of Bacteriology 1993;
175
(11).3247-3252).
[0006] Other than eventually transforming into an unsightly mineral
deposit (i.e., tartar,
also known as calculus), on teeth, the presence of plaque-biofilm on teeth is
undesirable
because the bacteria that grow in plaque biofilm are often pathogenic and
responsible for
various oral diseases, such as dental caries, gingivitis and periodontitis.
There is also
growing evidence that various human systemic diseases, such as infective
endocarditis,
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cardiovascular disease, arteriosclerosis, cerebrovascular diseases (i.e.,
diseases relating
to the brain including Alzheimer's disease and dementia), diabetes, as well as
many
others, are associated with the presence of certain bacteria in oral plaque
(Hiromichi Y
et at. The Pathogenic Factors from Oral Streptococci for Systemic Diseases,
Int J Mol
Sci, 2919:20, 4571: 1-18). In addition, gram negative bacteria in biofilm
produce
endotoxins that induce clinical manifestations of infection, i.e., local and
systemic
inflammation. Hence, control of plaque biofilm in the mouth is important for
maintaining
both good oral health and satisfactory overall human systemic well-being.
[0007] While many dentifrices are claimed to reduce the amount of
plaque-biofilm left
on teeth, clinical analyses have shown that toothbrushing with a dentifrice
generally does
not actually increase the amount of plaque physically removed compared with
brushing
without a dentifrice. (See, for example: (1) Valkenburg C et al. Does
Dentifrice Use Help
to Remove Plaque? A Systematic Review. .1 (lin Periodontal 2016; (2) Jayakumar
A et
al: Indian J Dent Res 2010; 21(2): 213-217; (3) Zanata FR et al: Supragingival
Plaque
Removal with and without Dentifrice: A Randomized Controlled Clinical Trial
Braz.
Dent J 2012; 23(3): 235-240. (4) Paraskevas S et al: Additional Effect of
Dentifrices on
the Instant Efficacy of Toothbrushing, J of Periodontology, 2006; 77(9):1522-
1572.
There are several reasons for this ineffectiveness, including the lack of
ingredients to
penetrate, entrap and displace biofilm from difficult-to-access areas on and
between teeth
and at the gumline. Furthermore, the ingredients in conventional toothpastes
are not
specifically designed to bind to bacteria or biofilm to facilitate detachment
from the tooth
surface, and thereby to eliminate them from the mouth with the expectorant
after
brushing is completed.
[0008] One trend in oral care research has been advancements in the
incorporation of
antimicrobials into mouthwashes and dentifrices. It has been shown that
appropriately
designed antimicrobial formulations can reduce plaque-biofilm regrowth between
brushings. In contrast, little if any, research seems to have been performed
to make
dentifrices more effective in physically displacing or removing plaque-biofilm
from teeth
during brushing or as a result of using oral rinses. As a result, 40% or 50%
of the plaque
present before brushing, usually remains on teeth immediately after brushing.
Rinsing
alone, as with a mouth rinse, is even less effective, because the forces
applied during
rinsing with a mouth rinse are relatively small and rinses are not designed to
promote
physical removal of plaque.
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[0009] One problem for anti-microbial agents is that oral bacteria do
not generally live
as individual planktonic cells that would be highly vulnerable to removal.
Instead, these
organisms join with organisms of many other strains to build complex
multispecies
biofilm-sheltered communities. Within the biofilm, nourished by ingested human
food,
bacteria rapidly synthesize high molecular weight polysaccharides and
glycoproteins,
which form protective matrices around the bacteria. These structures severely
limit the
access of antimicrobials to the organisms embedded within the protective
biofilm
matrices, and hence a large proportion of the microbes on tooth surfaces
survive
toothbrushing and remain viable after toothbrushing even when an anti-
microbial
dentifrice is used. Furthermore, over time, bacteria at the exposed surface of
biofilm
become increasingly resistant to antimicrobial agents. As a result, the
resistant organisms
in biofilms can become less susceptible to antimicrobials than planktonic
bacteria are, by
a factor of as much as 1000 Therefore, the human health benefits of
antimicrobial agents
tend to be quite limited.
[0010] Furthermore, the increasing use of antimicrobial substances in
personal care and
health care products has become a major evolving concern, because of its
potential to
promote the development and proliferation of antibiotic and antimicrobial
resistant
strains of bacteria. As a result, there is significant anxiety that this could
result in the
spread of more difficult to treat human diseases. Indeed, for this reason,
triclosan, a
widely used antimicrobial in personal care products, was relatively recently
removed
from toothpastes in the USA. Stannous fluoride, a fluoridating agent, which
has been
used for many years, also has significant antimicrobial activity and is still
employed in a
number of toothpastes. Perhaps, this is because up to now, there has been no
evidence
demonstrating that stannous fluoride produces genotypic changes in bacteria
leading to
resistance development.
[0011] In contrast to the use of antimicrobials, physically removing
more plaque biofilm
during brushing would not only have an immediate effect on lessening the
number of
pathogens present, but also would reduce biofilm regrowth, because less plaque
bacteria
would be present for reseeding new growth in the mouth.
[0012] In general, it is desirable that a toothpaste have as many as
possible of the
following attributes: remove dental biofilm effectively whether diluted or
not; avoids
damaging teeth; provides fluoride ions; and has pleasant esthetic properties
(taste, mouth
feel, etc.).
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[0013] Accordingly, the availability of a toothpaste, oral rinse or
other oral care
compositions in various dosage forms, which promotes physical removal of
plaque
biofilm, would be highly desirable. Also desirable would be a showing that a
product is
more effective in reducing the net amount of plaque left on teeth between
brushings.
Summary of the Invention
[0014] The oral care compositions disclosed herein are intended to
administer effective
amounts of plaque-dislodging components to promote the physical displacement
and
removal of plaque biofilm from teeth when applied together with kinetic
physical forces,
such as tooth brushing. The oral care compositions can be referred to as oral
hygiene
compositions. The reference to hygiene indicates that the composition is
conducive to
maintaining health and, if possible, avoiding disease and decay, by enhancing
cleanliness.
[0015] Compositions with these embodiments, comprise at least some of
the following:
(1) An oral plaque-biofilm-removing, water-insoluble, hydratable or partially
hydratable,
natural or synthetic, fibrillated, micro-fibrillated or nanofibrillated,
essentially non-
abrasive, polymer or network forming polymer, which swells and thickens in a
carrier
liquid, optionally together with one or more of the following additional
plaque removing
components; (2) A particulate, water-insoluble, micro-crystalline cellulose
(MCC),silicified micro-crystalline cellulose (SMCC) or other organic or
inorganic
particles; (3) A synthetic particulate cross-linked Super Absorbent Polymer
(SAP), or a
Natural, particulate, non-cross-linked Superabsorbent Polymer, which swells
and
thickens in an aqueous medium; (4) A water-insoluble, nano-crystalline
cellulose
polymer (CNC) derived, for example, by acidification or oxidation of a natural
or
synthetic cellulose; (5) A water-soluble, organic, polymeric, thickener (PT),
selected
from one or more of the following: an alkali metal or ammonium salt of a
polyacrylic
acid, an alkali metal or ammonium alginate salt, xanthan gum, guar gum,
carrageenan
gum, sodium carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl
methyl
cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose; (6) A natural or
synthetic
water-insoluble powdered cellulose (CP); and where the polymers form a 3D,
entangled
viscoelastic structure in an aqueous medium containing at least 10% of a
humectant and
which dislodges and removes plaque-biofilm from teeth The composition's
ingredients
are mixed, dispersed, suspended or dissolved in carrier ingredients, which
will vary
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depending on the type of oral composition and its desired characteristics or
dosage forms.
The components of these embodiments may be mixed, dispersed, suspended,
emulsified
or dissolved in a liquid carrier, or more generally any of various forms of
carrier. The
carrier liquid may include a humectant or a mixture of humectants.
[0016] Other embodiments can include, in any combination, any of
various performance-
broadening ingredients, which can address specific oral care needs of some
users, as
described elsewhere herein.
[0017] It has been found that when these compositions are brushed
across the tooth
surface, they increase the removal of bi ofilms by the toothbrush. In
contrast, conventional
toothpastes are generally ineffective in improving biofilm removal by the
toothbrush
when applied under similar conditions. Increased plaque-biofilm removal
results in
greatly improved oral health with less disease. Removal of plaque biofilm from
teeth by
regularly brushing with compositions of the invention will reduce gingival
inflammation,
prevent sub-gingival pocket formation, render the gum to be tightly adhering
to teeth,
decrease or eliminate bleeding gums and counteract bacterial challenges
leading to tooth
demineralization, tooth decay and tooth loss due to dental caries.
Importantly,
antimicrobial agents are not needed in these dentifrices, although they can
also be used
in some compositions.
[0018] The incorporated-by reference include Nonprovisional Patent
Application U.S.
Serial No. 17/062,424 filed October 2, 2020, discloses various useful oral
care
compositions. However, that disclosure does not appreciate the benefit of
using a
significantly greater amount of humectant, such as greater than about 5 wt.%
humectant
concentrations based on the weight of the composition. In regard to the
presence of
significant concentrations of humectant, it has been found that fibrils occupy
a
configuration or morphology that is different from what is seen with a water-
dominated
carrier liquid It is observed that in the presence of a high humectant
concentration, the
fibrils become well-distributed, whereas in a mainly-water carrier liquid,
there is some
tendency for the fibrils to clump together It is found that the humectant
changes the
structure of composition (compared to compositions having a mostly-water
carrier
liquid), promotes "fluffiness," of the fibrillated material and promotes
uniformity of
distribution of the fibrils, and aids entanglement. It is believed that, in
embodiments of
the invention, the spread-out nature of fibrils in a high-humectant carrier
liquid is
conducive to entanglement of fibrils with other fibrils and to trapping of
various kinds of
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particles in the entangled network formed by the fibrils. This entanglement
and trapping
is believed to help achieve better removal of plaque biofilm and other
undesirable matter.
[0019] Also disclosed herein are embodiments in which SuperAbsorbent
Polymer is
present in the composition, and the amount of water present in the as-
manufactured
composition is such that the SuperAbsorbent Polymer retains further ability to
absorb
water such as saliva, which, if not absorbed by the SAP particles, might cause
dilution
of the network during toothbrushing.
Brief description of the drawings
[0020] Aspects of embodiments of the invention may be further
understood, but in no
way are limited, by the illustrations herein.
[0021] Figure 1A is a micrograph showing a composition similar to an
embodiment of
the invention, in which microfibrillated material is dispersed in water,
showing the
existence of flocs and the existence of voids occupied by water.
[0022] Figure 1B is a micrograph showing a composition similar to an
embodiment of
the invention, in which microfibrillated material is dispersed in a water-
glycerol mixture,
showing a dispersal that is quite uniform.
[0023] Figure 1C is a micrograph showing particles of surface
crosslinked SAP,
dispersed in a composition of an embodiment of the invention.
[0024] Figure 1D is a micrograph showing a composition of an embodiment
of the
invention, in which particles of an abrasive are incorporated within the
fibrillated
network, and are generally absent in places were the network is absent.
[0025] Figure 1E is a micrograph showing a prior art commercial
abrasive-containing
toothpaste, showing that the particles of abrasive are distributed generally
throughout the
composition.
[0026] Figure 1F is a micrograph showing particles of MCC (PH200)
alone.
[0027] Figure 1G is a micrograph showing particles of MCC (PH200) in
the presence of
MIF C.
[0028] Figure 1H is a micrograph showing particles of SMCC
(SMCC50) alone.
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[0029] Figure 1I is a micrograph showing particles of SMCC (SMCC50) in
the presence
of MFC.
[0030] Figures 2A and 2B show a diagram of the tubing and flow
arrangement used for
testing biofilm removal inside a tube.
[0031] Figure 2C shows a cone and plate arrangement used for performing
tests of
biofilm removal using a disc in a rheometer.
[0032] Figure 3 is a series of photographs of stained biofilm
remaining after tube tests in
polytetrafluoroethylene tubes, illustrating the ranking of performance.
[0033] Figure 4A shows a hydroxyapatite disc.
[0034] Figure 4B shows a hydroxyapatite disc after cleaning with an
embodiment of the
invention.
[0035] Figure 5 shows, for commercial toothpaste, cleaning results on a
silicone tube,
and, for an embodiment of the invention, cleaning results on a silicone tube.
[0036] Figure 6 shows interiors of hydroxyapatite tubes before cleaning
(control), after
cleaning with commercial toothpaste, and after cleaning with a composition of
an
embodiment of the invention.
[0037] Figure 7 shows HA discs as a control and after cleaning with
various
compositions, with the biofilm being made by the shaker method. High
magnification
images were used for determining biofilrn coverage using the previously
described
process along with 5-7 other fields of the sample. Location of the image taken
is
shown with the box.
[0038] Figure 8 shows HA discs as a control and after cleaning with
various
compositions, with the biofilm being made by the flow method. High
magnification
images were used for determining biofilni coverage using the previously
described
process along with 5-7 other fields of the sample. Location of the image taken
is
shown with the box.
[0039] Figure 9 shows the linear viscoelastic response of a composition
made with 1.5%
MFC in water with 5% and 19% abrasive silica (Zeodent 113).
[0040] Figure 10 shows the linear viscoelastic response of a
prototypical toothpaste
prepared with various different liquid carriers (full concentration).
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[0041] Figure 11 shows the linear viscoelastic response of a
prototypical toothpaste
prepared with different liquid carriers (dilution 50%).
[0042] Figure 12A shows viscosity as a function of shear rate for two
embodiments of
the invention.
[0043] Figure 12B shows shear stress a function of shear rate for two
embodiments of
the invention.
[0044] Figure 12C shows G', G- as a function of the oscillatory shear
stress for two
embodiments of the invention.
[0045] Figure 12D shows G', G" as a function of angular frequency for
two
embodiments of the invention.
[0046] Figure 12E shows viscosity as a function of shear rate for two
embodiments of
the invention diluted 50% with water.
[0047] Figure 12F shows G', G" as a function of the oscillatory shear
stress for two
embodiments of the invention diluted 50% with water.
Detailed Description of the Invention
General concepts and definitions
[0048] The term concentration as used herein refers to concentration by
weight % of
ingredient in the composition. Water concentration in the composition includes
all
water present in the composition, whether it was introduced as water or as
part of a
sorbitol 70 solution (a condition in which sorbitol is often supplied) or as
part of
microfibrillated cellulose (which is often supplied in the form of a paste or
suspension
rather than completely dry). Fractional dilution refers to an amount of
commercial
toothpaste or an intended formulation, combined with an amount of water. For
example, herein, 25% dilution means that the final diluted toothpaste contains
25% the
original composition and 75% additional water.
[0049] In embodiments of the invention, the composition may comprise a
plurality of
fibers that form an entangled network. When the composition flows or moves or
is caused
to flow or move, the entangled fibers of the network move so as to bring along
other
fibers of the network or even other parts of the same fiber. Other solids that
are contained
within the network similarly may be brought along. It is believed that as a
toothbrush
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moves over the surface the toothbrush applies normal force that promotes
contact of the
fibers and solids with biofilm or other surface-contacting substances, so as
to facilitate
the removal of such substances from the tooth or other surface. Also, motion
of the
toothbrush creates a shear stress during flow. In embodiments, the fibers may
be either
non-fibrillated or fibrillated.
[0050] In embodiments of the invention, compositions may comprise
fibers or fibrils that
are fibrillated, in which smaller fibrils branch off from larger fibers. Such
fibers based
on natural or synthetic microfibrillated or fibrillated cellulose or other
forms of
polysaccharides or other cellulosic or non-cellulosic polymers which form an
entangled,
interconnected or joined three-dimensional network structure. The joined
entities
forming the network can be fibers and fibrils and can be a network-forming
material as
provided elsewhere herein.
[0051] Other solids may also be present. Also, there may be a liquid
vehicle having
ingredients and properties as described herein.
[0052] Compositions of embodiments of the invention are intended to
provide a
viscoelastic oral care composition, such as a toothpaste that helps deliver
the plaque
dislodging and removing ingredients to the biofilm being removed. Compositions
of
embodiments of the invention have a yield stress and have an elastic modulus
or storage
modulus and a loss modulus even when diluted as described herein. It has been
found
that when these compositions are caused to flow over a surface, they remove
biofilms. In
contrast, prior art oral care compositions, such as commercial toothpastes,
were found to
be ineffective when used under similar conditions. Embodiments of the
compositions are
expected to significantly improve oral hygiene and reduce gingivitis, tooth
decay and
tooth loss. It is believed that the operating mechanism of a network of
fibrillated material
in removing biofilms is not present in conventional toothpastes.
[0053] In connection with work described herein, it has been found that
measurements
of rheology and tribology of candidate compositions are useful in the
development of
formulations and compositions of the invention. However, compositions having
identical
rheology and tribology do not necessarily clean identically. In particular,
compositions
of embodiments of the invention clean better than conventional toothpastes
having the
same or closely similar rheological and tribological properties. In other
words, satisfying
the requirements of rheology and tribology of the composition before and after
dilution
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may be considered necessary but not sufficient to remove plaque biofilm, and
certain
ingredients in the composition are required to make effective compositions
according to
the invention.
[0054] In general, compositions of embodiments of the invention may
comprise
ingredients of various different categories. In the following, description is
given of
categories of ingredients that are sometimes found in prior art toothpastes or
that may be
present in embodiments of the invention.
Fibrillated Material
[0055] Embodiments of the invention comprise material that may form an
entangled
network. The network is believed to be effective to contribute to the
rheological
properties described herein, and is believed to contribute to effectiveness in
removing
dental plaque, even in diluted form such as during bnishing where a
significant dilution
by saliva takes place. In embodiments, the network may contain fibers that are
entangled
with each other.
[0056] In embodiments, the Minute Fibrils may be fibrillated, meaning
that they
comprise thicker fibrils, from which branch thinner fibrils. In embodiments,
the thinner
fibrils, by being entangled, may be part of the entangled network. The thinner
fibrils may
remain attached to the thicker fibrils, such as attached at one end while the
other end of
the fibril is unattached. Other configurations are also possible. Unattached
discrete fibers
or fibrils may also be present.
[0057] The terms MicroFibrillated Cellulose and NanoFibrillated
Cellulose are
sometimes used interchangeably, and herein both terms are intended to be
interchangeable and to be included in the meaning of the term Minute Fibrils.
[0058] In embodiments, the Minute Fibrils may comprise a
polysaccharide. In
embodiments, the Minute Fibrils may comprise cellulose. Cellulose is a
polysaccharide
that is created by plants, and also is created by bacteria or other organisms
including
fungi. Chemically, cellulose comprises polymeric chains of cellobiose dimers,
which
each comprise two glucose units. The cellobiose units are connected through
beta-( 1-4)
linkages to form long chain polymeric molecules containing up to several
thousand
cellobiose units. The long polymeric chains form a three-dimensional macro-
network of
cellulose fiber chains, which have a mixture of amorphous and crystalline
regions. By
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amorphous, we mean that the polymer constituents are highly disordered. In
contrast
crystalline cellulose" refers to cellulose chains, which are highly regular
and ordered.
With reference to crystalline cellulose, its crystallinity should not be
confused with the
type of crystallinity found, for example, in a crystalline inorganic salt.
Crystalline salts
are rigidly held together by strong attractive ionic forces. As a result,
ionic crystalline
salts are formed into hard, highly ordered, essentially immobile, ionic
crystal matrices.
While crystalline cellulose is quite well ordered, its structure is not ionic
and the
polymeric cells, i.e., individual cellobiose units, are held together by
somewhat elastic
hydrogen or covalent bonds. As a result, while "crystalline" organic polymers,
are more
"rigid" than amorphous organic polymers, they are still more flexible than
inorganic
crystalline salts and they remain somewhat mobile. From a macroscopic
standpoint,
crystalline salts appear as hard solid particles, while microcrystalline
cellulose is softer
and more fabric-like. Of importance to the performance of micro-fibrillated
cellulose for
plaque-biofilm removal, the flexible fibrils and microfibrils on cellulose
fibers, absorb
water, expand and form an entangled flexible, network structure when added to
an
aqueous medium. In addition to trapping plaque and removing it from surfaces,
the
structure is believed to importantly contribute to the mechanical properties
of the
composition, which ensures that the applied forces of brushing or rinsing,
reach and
dislodge the plaque-biofilm from surface of teeth and elsewhere in the oral
cavity.
[0059] While the vast majority of cellulose used in the world is
derived from plants, it is
worthwhile mentioning that some cellulose is obtained from or is excreted by
bacteria,
and is referred to as bacterial cellulose. Such cellulose typically has
dimensions smaller
than the dimensions of other types of cellulose described herein. Bacterial
cellulose may
be used in embodiments of the invention.
[0060] Fibrillated cellulose as described here can be made from any of
various types of
wood or plants. MFC can be of plant origin such as that made by Borregaard
(Sarpsborg,
Norway), Weidmann Fiber Technology (Rapperswil-Jona, Switzerland) and many
other
manufacturers in many countries. The Borregaard material, which is sold under
the
tradename "Exilva," is made from Norwegian Spruce. The Weidmann material,
which is
marketed under the tradename "Celova,- is made from Swiss Birch. Cellulose
products
are also available from Sappi (Boston, MA, USA). The Sappi micro-fibrillated
cellulose
is made from wood pulp and other natural sources. In general, the material is
not limited
by species of tree or plant. Dimensions of the fibrillated cellulose that can
be used in the
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present composition are provided in Tables 1 and 2 in US 10,266,793. Tables 1
and 2
from US 10,266,792 are reproduced below as Tables 1A and 1B.
[0061] Materials made by Borregaard have subclassifications
including:
[0062] Table lA
Sub-Grade Mean Hydrodynamic size
Size Range
Exilva Forte ¨20 micron ¨1 to
¨1000 micron
Exilva. Piano (various ¨36 to ¨60 micron
¨1 to ¨1000 micron
grades)
Exilva Piano Light ¨70 micron ¨1 to
¨1000 micron
Sensifi (in admixture ¨100 micron ¨1 to
¨1000 Itlier0I1
with CNIC)
[0063] As analyzed by numerous SEMs at several magnifications, some
illustrative
cellulosic Minute Fibrils have the following features:
[0064] Table 1B
Microfibri Ilated Fibers (Type. B) Fibrils
(Type A)
Cellulose
Diameter Length Diameter Length
Exilva Forte 0.5-3 um 10-
100 p.m 30-60 tun >2 pm
Exilva Piano 0.1-20 um 5-150 gm 50-
70 mu 2-3 p.m
Microfibrillated Fibers (Type B)
Fibrils (Type A)
Cellulose Diameter Length = zr,
Diameter Length
Exi Iva Piano 0.3-20 pm 20-
200 pm 20-75 um .1-5 p.m
Light
Sensefi 0.25-15 p.m 5-
60 um 30-60 nm 0.4-1.0 p.m
[0065] It may be preferable to process the wood or other plant-based
source of cellulose
to form MFC using processes that are purely mechanical, without the use of
chemicals.
Alternatively, some other acceptable processes for making WC may include
exposing
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the material to enzymes or other chemical compounds that can be washed out
after
processing. Both types of processing can be used in combination.
[0066] A particularly preferred fibrillated polysaccharide component is
micro-fibrillated
cellulose (MFC), which can be prepared from wood cellulose pulp fibers by
opening and
separating its fibers and microfibrils. It should be noted that the terms
micro-fibrillated
cellulose and nano-fibrillated cellulose are sometimes used interchangeably.
When we
refer to micro-fibrillated cellulose or Minute Fibrils, we also mean to
include nano-
fibrillated cellulose. Other cellulose sources and mechanical, chemical,
bacterial,
biological or enzymatic processes can also be used in making the composition
of
embodiments.
[0067] Fibrillated and micro-fibrillated polysaccharides other than
cellulosic polymers,
and other non-cellulosic polymers (irrespective of their size) can also be
used as the
micro-fibrillated plaque-dislodging polymer, providing they are essentially
water-
insoluble. In addition to wood/plant sources of MFC, other suitable natural
polysaccharides include ground peanut shells, corn cobs, and ground hay or
straw, which
may contain mixtures of water-insoluble polysaccharides such as cellulose,
hemicellulose and lignin. Also, it is possible to use chitosan or its
derivatives, which is
another form of polysaccharide. US Patent No. 6,602,994 (EP 845495 and JP 59-
84938)
refers to the formation of an insoluble micro-fibrillated polymer made by the
homogenization of chitosan flakes Such a microfibrillated polysaccharide would
be
suitable for preparing embodiments of the composition. In still other
embodiments of the
invention, the fibrillated material could comprise still other polysaccharides
other than
cellulose. Other fibrillated material may also include those made from
polyethylene,
polypropylene, polyester, nylons,amides or any synthetic polymer. These may be
used
either alone or in combination with other Minute Fibril materials. At least
one version of
the wood-sourced material is approved by the United States FDA as a food or
being
GRAS (i.e., Generally Recognized as Safe).
[0068] For example, suitable starting materials can include a broad
range of
polysaccharides. The resulting fibrous materials are similar in structure and
size to the
fibrillated and micro-fibrillated cellulosic materials described above and
hence are
effective in plaque biofilm-removing embodiments described herein. The water-
insolubility of micro-fibrillated polysaccharides can be confirmed by
suspending the
ingredient at a concentration of 1-5% in distilled water or other solvents
such as glycols
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or the like, and examining the suspension under a microscope as described in
US Patent
No. 6,602,994, or by measuring the rheology and tribology of the resulting
materials and
its response to dilution as described elsewhere herein.
[0069] Yet another possibility for embodiments of the invention is that
the Minute Fibrils
may be or may comprise cellulose that is of bacterial or microorganism origin.
Such
cellulose may provide biocompatible fibrillated material that may be used
alone or mixed
with other fiber-based materials to form the network of the present invention.
Typically,
fibers of such cellulose typically have smaller cross-sectional dimensions and
other
detailed microstructural features than the fibers that are fibrillated from
plant-based
starting materials.
[0070] As yet another alternative, the fibrillated material can be also
non-cellulosic such
as material made from synthetic or man-made polymers such as flocked nylon or
polyester, polyolefins, acrylic or other polymers. The fibrillated materials
may be made
by the Viscose or Lyocell process, in which fibers are spun from cellulose-
based
polymers or other synthetic polymer materials dissolved in special solvents.
Such fibers
are produced, for example, by Engineered Fibers Technology (Shelton, CT, USA).
[0071] Still other possible microstructural network forming materials
that can be used to
make the inventive compositions include the following:
i) Polypropylene fibrils see article by Rizvi et al. (2014) Dispersed
polypropylene
fibrils improve the foaming ability of a polyethylene matrix. Polymer, 55
(16), 4199-
4205.
ii) Proteins Fibrils, see for example Adamcik, J., & Mezzenga, R. (2012).
Proteins
fibrils from a polymer physics perspective. Macromolecules, 45(3), 1137-1150.
In their
specific example/protein, to be used at 5% wt and beyond
iii) Amyloid fibrils, see Volpatti, L. R., & Knowles, T. P. (2014). Polymer
physics
inspired approaches for the study of the mechanical properties of amyloid
fibrils Journal
of Polymer Science Part B: Polymer Physics, 52(4), 281-292.
iv) Fibrillated holocellulose see Yang, X., & Berglund, L. A. (2020).
Structural and
Ecofriendly Holocellulose Materials from Wood. Microscale Fibers and Nanoscale
Fibrils. Advanced Materials, 2001118.
v) Fibrillated block copolymers, see Hammer, B. A., Bokel, F. A., Hayward,
R. C.,
& Emrick, T. (2011). Cross-linked conjugated polymer fibrils: robust nanowires
from
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functional polythiophene diblock copolymers. Chemistry of Materials, 23(18),
4250-
4256.
vi) Collagen fibrils, see Van Der Rijt, J. A., Van Der Werf, K. 0.,
Bennink, M. L.,
Dijkstra, P. J., & Feij en, J. (2006). Micromechanical testing of individual
collagen fibrils.
Macromolecular bioscience, 6(9), 697-702.
vii) methylcellulose fibrils, see Morozova, S. (2020). Methylcellulose
fibrils: a mini
review. Polymer International, 69(2), 125-130.
viii) Fibers made from alginates by crosslinking with multivalent ions as is
known in
polymer chemistry.
ix) Fibers and networks made mixing polymers such as methyl cellulose and
hydroxyethyl cellulose using nanoparticles as a crosslinking agent by either
ionic or
hydrogen bonding.
x) Fibers and networks that are made by ionic, acid-base, or hydrogen
bonding or
by crosslinking of polymer molecules.
xi) Fibers and networks made by mixing polymers and ions to form
coacervates; ions
may include borates or other ions as is known in polymer chemistry.
xii) Any combination of the above alternate routes for making fiber and
networks.
[0072] Still other possible microstructural network forming materials
that can be used to
make the inventive compositions include the following:
i) Chitosan (concentration between 0.1% to 10%, preferably between 0.3 and
8%)
and particles like MCC or abrasive silica.
ii) Chitosan (concentration between 0.1% to 10%). Mechanical properties
changing
depending on the pH.
iii) Synthetic micro-sized biocompatible flexible fibers, fibrillated or
not, made of
PEG or PEG-DA through chemical/UV-photo-activated cross-linking. See article
by Perazzo el al. (2017). Flow-indnced gelation of rnicrofiher cn.spensions.
Proceedings of the National Academy of Sciences, 114(41), E8557-E8564.
iv) Dual networks of polymer hydrogels. See examples of polymers from JP
Gong
papers. Though concentrations must be modified because they produced stiff
gels, while here we want to use smaller elastic modulus.
v) Interpenetrated polymer networks. See examples provided by JP Gong
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vi) Interpenetrated polymer networks made of chemically linked by colloidal
silica
nanoparticles: example hydroxyethylcellulose (My ¨1,300 or 720 kDa;) and/or
methyl cellul ose (Mv ¨90 or 60 kDa; Sigma) in water ( I -20 mg/mL) with
stirring
and mild heating. Colloidal silica nanoparticles at about 1-30% wt [Ludox TM-
50; D ¨15 nm] then (150 mL) of the FfEC and MC solution is mixed with the
colloidal nanosilica solution (300 mL). See paper by Anthony, C. Yu, et al.
"Scalable manufacturing of biomimetic moldable hydrogels for industrial
applications." Proceedings of the National Academy of Sciences 113.50 (2016):
14255-14260.
vii) Cellulose nanocrystal suspensions and related pH effects see Tony
examples
viii) Laponite based gels and other clay systems see Au, P. I., Hassan, S.,
Liu, J., &
Leong, Y. K. (2015). Behaviour of LAPONITE gels: theology, ageing, pH effect
and phase state in the presence of dispersant. Chemical Engineering Research
and Design, 101, 65-73.
ix) Polyelectrolyte coacervates/complexes, i.e., mixture of positively
charged and
negatively charged polyelectrolytes
x) PVA acrylic acids cross-linked by borates or Zr. See examples on paper
by
Perazzo et al, Advances in Colloid and Interface Sciences, 2018
xi) Polyelectrolyte plus salts/multivalent salts such as Y or Al
xii) Surfactant plus polyelectrolyte complexes.
xiii) Surfactant worm-like micelles such as combination of CpyCl surfactant
and NaCl
or CTAB surfactant and NaCl or NaSal, see examples by Gaudin et al., Journal
of Rheology, 2015
xiv) Emulsions, i.e., oil-water mixtures where on phase is present in forms of
droplet
dispersed into the other phase. Stabilized by surfactants or mixture of them,
as
the ones mentioned in the surfactant list for toothpaste.
xv) Bicontinuous emulsions, i.e., oil-water mixtures where on phase is
compenetrated/percolated into/though the other phase. Stabilized by
surfactants
or mixture of them, as the ones mentioned in the surfactant list for
toothpaste.
xvi) Nanoemulsions, i.e., emulsions with droplet size smaller than 200 nm.
xvii) Microemulsions, i.e., thermodynamically stable emulsions where the
interfacial
tension is close to zero
xviii) Pickering emulsions, i.e., emulsions stabilized by colloidal particles
or fibers.
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xix) Bij els. Compenetrated immiscible gel phases mostly stabilized by
colloidal
particles.
[0073] Linear or branched worm-like surfactant micelles ranging from
about 0.1 nm in
to 100 nm in diameter and having an aspect ratio of more than 2, such as for
example
those made with: a) combinations of cetylpyridinium chloride surfactant and an
electrolyte/salt such sodium chloride (e.g. NaCl); b) cetyltrimethylammonium
bromide
(CTAB) surfactant and NaCl, or c) activated by a pII change and/or electrolyte
can be
used as network-forming compositions according to the present invention.
Examples for
making worm-like micelle (WLM) structure is described by Dreiss, Soft Matter
2007;
Chu et at. (2013). Smart wormlike micelles. Chemical Society Reviews, 42(17),
7174-
7203; Dreiss, C. A., & Feng, Y. (Eds.). (2017). Wormlike Micelles: Advances in
Systems,
Characterisation and Applications. Royal Society of Chemistry; Gaudino et at.,
Journal
of Rheology, 2015.
[0074] While there are several effective ways to fibrillate cellulose,
a preferred method
involves passing the cellulose pulp fiber source material several times
through a special
high-shear or impact generating homogenizer or microfluidizer (see, for
example
methods of Turbak et al. in US Patent 4,341,807; US Patent No. 4,374,702; US
Patent
No. 4,378,381; and US Patent No.4,500,546).
[0075] In embodiments, the fibrillated materials can be surface
modified by physical
means such as adsorption of a surfactant, an ion, a polyelectrolyte, a
molecule or a
polymer or can be chemically modified to introduce special functional groups
to the
surface of the fibers and fibrils. The MFC may be functionalized such as by
oxidation as
by the TEMPO manufacturing process or by other chemical reactions including
amidation, amination, hydrophobization or the like, if desired. (A Review on
Surface-Functionalized Cellulosic Nanostructures as Biocompatible
Antibacterial
Materials; Tavakolian, et al., Nano-Micro Lett. (2020) 12:73) The modification
processes
maybe through physical adsorption, or through a chemical reaction to introduce
special
functional groups into the surfaces of the fibers and fibrils. Some cellulosic
materials
may be material having amine cationic groupings, which makes them likely to
provide
anti-microbial activity to dentifrice compositions containing this ingredient.
Cellulose
polysaccharides can be "derivatized" and micro-fibrillated, as described in
the same US
Patent (US Patent No. 6,602,994 to Cash). By "derivatized" we mean imparted
with
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functionality either before or after being micro-fibrillated to produce the
desired forms
similar to microfibrillated cellulose. Non-cellulosic polymers capable of
becoming
fibrillated are also available, although they are less commonly available from
natural
sources than cellulose.
[0076] In regard to dimensions, the thicker fibrils of MFC may have a
diameter between
about 0.1[tm to about 25 p.m and preferably from about 0.25 i.tm to about
20[Im or larger.
The thinner fibrils may have a diameter between about 250 nanometers to about
20
microns. As described in US20180078484, in particular embodiments, the average
MEC
fibril length may be from 100 nm to 50 p.m, preferably from 500 nm to 25 p,m,
more
preferably from 1 jim to 10 p.m, most preferably from 3 p.m to 10 pm. In
particular
embodiments, the average MEC fibril diameter may be from 1 nm to 500 nm,
preferably
from 5 nm to 100 nm, more preferably from 10 nm to 50 nm, most preferably from
10
nm to 30 nm. For dentifrices of this embodiment, an average mean particle size
(which
may be determined by laser diffraction) should be between about lOtim and
about
150 m, more preferably between about 201Lim and 100p.m. These dimensions can
be
modified as required by varying the production process parameters such as the
number
of passes of the cellulose pulp fibers through the refiner and the
microfluidizer/grinder/milling devices or similar equipment. The dimensions of
the
resulting fibrils may be tailored depending on the degree of fibrillation as
dictated by the
amount of mechanical energy used to fibrillate the source fibers, for example
the number
of passes through the microfluidizer machine, as is known in the art of making
micro-
and nanofibrillated cellulose.
[0077] The desirable MEC may have a high degree of fibrillation, which
is a function of
the number of passes through the microfluidizer, the gap size used and the
pressure of
fluidization. A number of passes of about 5 passes or more than 5 passes may
be
recommended, more preferably from 5 to 15 passes. The degree of fibrillation
can be
assessed by: a) number and size fibrils made from source fiber; b)
hydrodynamic size as
determined in a dilute state by laser diffraction; c) the viscosity and
rheology of the
resulting structure in water or in ethylene glycol; d) water holding capacity
as determined
by centrifugation at, for example, 3,000 to 10,000 g; e) specific surface area
expressed
in m2/g as measured by the BET (Brunauer-Emmett-Teller) method. The average
hydrodynamic size as determined by laser diffraction may be from .51Lim to 100
pm
depending on the degree filtration and preferably from 20 to 70 p.m. The size
distribution
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as determined by laser diffraction may include particles up to 100 mm or 200
[tm or even
close to 1 mm. It should be noted that the hydrodynamic size may be that of
flocs formed
by aggregation of a number of fibrillated entities. The specific surface area,
as measured
according to the BET method, may be from 50 m2/g to 300 m2/g or even 500 m2/g.
The
viscosity of a 2% by weight concentration of MFC in water may be from 10,000
to 50,000
mPa-s when measured with a Brookfield viscometer using the V73 spindle at 10
rpm
after 5 minutes.
[0078] It can be noted that materials such as fibrillated cellulose
have a property of being
able to hold or retain water among the fibrils. The desirable MFCs or
polysaccharides for
dentifrices have a high degree of fibrillation and a water holding capacity,
such as from
about 20g/g to about 300g/g (grams of distilled water per gram of dry MFC),
preferably
from about 50g/g to about 150g/g (available from Borregaard). Measurement of
water
holding capacity is described in US20180078484. Commercially, micro-
fibrillated
cellulose is typically shipped in the form of a stable paste containing from
about 9% to
about 11% micro-fibrillated cellulose in water; some other suppliers can
provide MFC
concentrations pastes of up to 30% to 35% concentration. This is because if
water was
removed from MFC until the product was completely dry, the drying would
decrease the
ability of the MFC ability to re-disperse in water. Related to this, if MFC
that has been
fully dried and then redispersed in water, the viscosity and other rheological
parameters
of that MFC in liquid are much lower or inferior, compared to the properties
that existed
before the MFC was dried. We note that the use of humectants prevents
irreversible
aggregation or hornification of cellulose fiber and fibrils upon drying, and
this could be
used to allow the creation of microfibrillated cellulose having little or no
water content,
without causing break-up or damage of the fibers or fibrils. This could be
used in making
compositions for oral use such as for chewing gum or other applications. US
Patent
4,481,077 describes drying and redispersion of fibrillated material.
[0079] The specific surface area of MFC, may be characterized by the
BET (Brunauer-
Emmett-Teller) method. The specific surface area of the MFC may be chosen to
be in
the range from between about 10m2/g to about 500m2/g, preferably from about
50m2/g
to about 350m2/g. In general, MFC with a larger specific surface area will
provide a
higher aqueous solution viscosity, higher G', higher yield stress, greater
absorption,
increased binding of biofilm, and hence better plaque and soil removal.
Furthermore, a
larger specific surface area indicates that the MFC will be more resistant to
loss of
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viscosity due aqueous dilution such as due to incoming saliva during brushing.
Hence,
one disadvantage of this increase of solution viscosity with increasing
specific surface
area can be the inability to formulate compositions containing very high
concentrations
of MFC, which would result in compositions that are extremely thick (viscous)
and
difficult to dispense.
[0080] It is known that materials such as MFC experience a process
called activation
upon being subjected to high shear or torque, which can be obtained with a
homogenizer.
Activation causes entanglement of the Minute Fibrils to form the inventive
entangled
networks present in compositions of embodiments of the invention. For small
batches,
we used an Ultra Turrax T25 homogenizer (available from IKA Works, Inc.,
Wilmington, NC) With this homogenizer we used the following dispersing head
model
numbers: S25N-18G; S25N-25F; and S25KV-25F. Typical rotational speeds and
durations of homogenization were 10,000 to 20,000 rpm and 10 to 30 minutes or
until
equilibrium rheol ogi cal properties are obtained For larger batches, we used
a Ross
homogenizer (Charles Ross & Son Company, Hauppauge, NY) or other equivalent
equipment.
[0081] As discussed elsewhere herein, it may be advantageous for there
to be a
considerable degree of entanglement of the Minute Fibrils with each other,
which may
produce a better cleaning interaction when applied to surfaces. It is believed
that the
mechanical shearing or homogenization during activation of the inventive
composition
encourages and increases entanglement of the fibrils. Thus, in order to
describe a
composition of an embodiment of the invention, one may describe not just
chemical
composition and dimensions or dimensional distribution of the fibrils, but
also the extent
of entanglement as a result of manufacturing processes. During manufacture of
the
described composition of embodiments of the invention, the entangled network
of the
inventive composition may be formed by homogenizing MFC and possibly other
ingredients in the presence of water, water-humectant mixtures or more
generally liquid,
under shear so as to form physical entanglements.
[0082] Such activation process may be a process that is distinct and
separate from the
process used in fibrillating the material. The activation process may be
performed after
the fibrillation process. Other manufacturing, mixing or processing steps may
be
performed in between.
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[0083] It is believed that, due to its interconnected entangled
microstructure, MFC does
not shed fibers, fibrils or particles when diluted in water as can occur
during brushing,
rinsing or cleaning. Such physical entanglements resist being unraveled by
dilution when
the composition is later used in the mouth. Resisting being unraveled by
dilution is a
property of compositions of embodiments of the invention, in contrast with the
behavior
of commercial toothpastes that are made with polymeric thickener (mainly
macromolecules and particles). Such commercial toothpastes readily fall apart
and
disassemble into slurries when they experience even slight dilution by water
or saliva.
Other fibrous material
[0084] It is also possible, in embodiments of the invention, that the
fibrils may be simple
fibers that are non-fibrillated. In such case, the fibers may be sufficiently
long, as
described by an aspect ratio, and appropriately processed, to form an
entangled network.
Non-fibrous solid material
[0085] In an embodiment of the invention, the composition may include
non-fibrous
solids or non-fibrillated solids. Such ingredients, which may be particles or
particulates,
may modify rheology, tribology, and microstructure and can impact physical,
mechanical
or chemical properties of the composition so that it can remove biofilm,
stain, residues
or other substances from teeth and the oral cavity. Such ingredients also may
produce
effects such as whitening or lowering sensitivity or other desirable
attributes as described
elsewhere herein. Materials that can be in the category of non-fibrillated
solid material
includes MicroCrystalline Cellulose and abrasives, and other types of solids.
In general,
they can be used in any combination and in any concentration.
[0086] Frictional interaction with the surface being cleaned can be
created by either or
both of, the fibers and fibrils of the fibrillated material, and other solids
that may be
present in the composition. If these other solids resemble fibers, such fibers
may be
unbranched in contrast to the fibrillated material described elsewhere herein,
or they may
be less branched than the fibrillated material. It is believed that these
solids may
contribute to plaque and stain removal by the composition. Such solids have
been shown
to synergize with the network of polymeric fibers in displacing plaque biofilm
during
brushing. These particulate solids may be one or more natural or synthetic,
non-
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scratching, water-insoluble, particles, fibers or fibrils, which may for
example be
polysaccharide.
Microcrystalline cellulose
[0087] A useful type of additional solid is a non-fibrillated,
particulate, water-insoluble
micro-crystalline cellulose (MCC). Chemically, MCC is similar to MFC or
cellulose in
general, in that it consists of polymeric chains of dimeric cellobiose. The
primary
chemical difference between MCC and MFC is the significantly higher content of
cellulose in crystalline form in MCC. Also, from a physical standpoint, in
contrast to
MFC, the cellulose strands or macrofibrils in MCC are not fibrillated. As a
result,
although the MCC particles do not have high hardness, they are more rigid or
more stiff
(with respect to bending) than is fibrillated forms of cellulose, and are
suitable for
enhancing rheology and applying mild frictional forces to wipe or mop the
plaque biofilm
from tooth surfaces. The long, highly flexible fibrils of MFC may be suited to
reaching
into inaccessible areas and entrapping plaque biofilm and dislodging it.
[0088] Included in the category of micro-crystalline cellulose (MCC),
is silicified micro-
crystalline cellulose (SMCC), which contains particles containing micro-
crystalline
cellulose coated or mixed with colloidal silicon dioxide (silica). SMCC
performs the
same function as MCC, i.e., to provide mild frictional forces to remove
biofilm from
tooth surfaces. However, MCC has a tendency to form particulate clusters or
agglomerates, which do not always easily break down during preparation of the
composition to form a smooth composition. SMCC provides a useful alternative
that is
more readily dispersed in a paste formulation. The most popular form of MCC is
Avicel , which was invented by FMC Corporation (Philadelphia, PA) and now is a
product of Dow (Midland, MI). Various grades of MCC and SMCC also are
available in
the USA from IRS Pharma LP, (Patterson, NY) and are manufactured under the
Trade
names, Vivapur MCC and Vitacel MCC and Prosolv SMCC. Vivapur MCC is
available with average particles sizes between about 15 . and 250 . For
dentifrices of
this embodiment, preferred particles sizes are between about 15ii and 125t and
also
200um. Prosolv SMCC is available with various average particle sizes between
50 .
and 125 .. The average particle sizes of SMCC for these embodiments may be
chosen to
be between about 30[1 and about 125i, and preferably between 50p, and 100 t,
more
preferably between 60 and 84.
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[0089] Particles such as MCC may be elongated or irregular shape. Such
particles may
have at least one dimension that is larger than 25 microns or larger than 50
microns
(average). The size could be up to 200 microns or larger. Such particles may
have an
aspect ratio (ratio of maximum dimension to minimum dimension) that is larger
than 2
or larger than 3. In embodiments of the invention, the concentration (w/w) of
particles
such as MCC or SMCC may be at least as large as the concentration(w/w) of
Minute
Fibrils, or may be at least half the concentration(w/w) of Minute Fibrils. In
embodiments
of the invention, the concentration (w/w) of MCC particles may be 0.2% (w/w)
or more,
or 0.5% or more, or 0.6% or more. In some embodiments, the concentration (w/w)
of
MCC particles is 1.2% (w/w) or less. In some cases, particles such as MCC at a
concentration up to 5% or 10% may further modify the storage modulus or
stiffness of
the composition.
[0090] In some conventional commercial toothpastes MCC is known to be
included, but
it is believed that in those conventional commercial toothpastes the MCC is in
the form
of very small particles such as smaller than 25 microns or smaller than 50
microns or
even can be in the form of what is referred to as colloidal MCC such as 3 or 4
microns
or even smaller, and it is present at a small concentration. It is believed
that in the
commercial toothpastes, which are based on polymeric thickeners such as
carboxymethylcellulose (CMC), the type of MCC that is used is unlikely to
provide a
wiping or biofilm removal effect, because of small particle size and low
concentration.
[0091] Other organic or inorganic particles also can possibly be used.
These other
particles, including both organic particles and inorganic particles, can be
used
irrespective of their shape and sizes. Additional water-insoluble cellulosic
materials
which can be used are ground peanut shells, consisting primarily of cellulose
and
hemicellulose polysaccharides with some lignin (reference: Kerr JI, Windham
WR,
Woodward JH and Benner R: Chemical Composition and In-vitro Digestibility of
Thermochemically Treated Peanut Hulls. J. Sci. Food Agric. 1986; 37: 632-636)
are also
useful in the enhancement of plaque-biofilm removal. Pulverized corn cobs,
which
comprise mixtures of cellulose, hemicellulose and lignin, can also be used
(reference:
Pointner M, Kuttner P, Obrlik T et al: Composition of corncobs as a substrate
for
fermentations of biofuels. Agronomy Research 2014; 12(2): 391-396) Ramie is
another
example of a natural material which provides useful particulate fibers, which
can be
extracted from the inner bark phloem of ramie plant stems and degummed. Useful
fibrous
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materials can also be obtained from Jute, the Java tree, flax and abaca fiber,
psyllium,
and other sources.
[0092] In an embodiment of the invention, these solids can be entangled
in the network
created by the Minute Fibrils, and thus the solid particles might not exist as
loose freely-
moving individual particles, which is what occurs in the case of conventional
commercial
toothpaste where the particles quickly become loose in the form of slurry once
they are
diluted with saliva water in the mouth. The various types of particles of
embodiment
compositions, being a part of the network, are believed to contribute to
removal of plaque
and stain by interacting with plaque biofilm or stain, such as by scraping or
by creating
localized forces at the surface that further improve the removal of plaque
biofilm and
stain as described elsewhere herein.
[0093] If the concentration of abrasive particles is taken together
with the concentration
of various other kinds of particles, the total concentration of various kinds
of particles
may be up to 30% or higher by weight of the composition.
Other forms of cellulose
[0094] Another optional plaque dislodging ingredient in embodiments of
this
composition is a water insoluble nanocrystalline cellulose polymer or
cellulose
nanocrystals (CNC), which can be derived by combinations of mechanical,
chemical and
enzymatic treatment of cellulose (Johnsy G: Cellulose Nanocrystals: Synthesis,
Functional Properties, and Applications. Nanotechnology, Science and
Application
2015;8: 47-54). Mechanical processes convert cellulose into micro-fibrillated
cellulose,
such as by micro-fluidization, ultrasonic treatment or homogenizations
methods. As
previously noted, micro-fibrillated and microcrystalline cellulose, consists
of long chains
of cellobiose units. Cellobiose is a dimer consisting of two glucose units. In
natural
cellulose, these disaccharides are formed into long polymeric cellobiose
chains.
Microfibrillated and other forms of cellulose can easily be modified into CNC
by acid-
hydrolysis to remove the amorphous regions and to convert them to crystalline
cellulose,
thereby increasing the crystalline cellulose content. This frequently shortens
the micro-
fibrils and hence the resulting cellulose is often referred to as
nanocrystalline cellulose.
CNC is characterized as being stiff rod-like particles with mostly a
crystalline cellulose
structure. The apparent stiffness of the shorter relatively stiff, rod-like
fibers is
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presumably due to their short length. Aqueous slurries of CNC generally have
lower
viscosities and lower yield stress than WC in aqueous systems. Due to CNC' s
stiffness
and rigidity, CNC may contribute somewhat greater frictional forces for plaque
biofilm
removal from tooth surfaces; because of its smaller particle size CNC may
readily flow
in the InterProximal space and produce biofilm removal. Nevertheless, CNC
particles
are still very soft and are not abrasive to surfaces.
[0095] The dimensions of CNC can vary depending on the source of the
CNC and the
method of manufacture. CNC from acid hydrolyzed wood fibers can have a fibril
length
of between about 100 and 300 nm. The widths of these fibrils can be from about
3 to 5
nm. Acid hydrolyzed, bacterial-sourced CNC has fibril length between 100nm and
1000
nm and a width between lOnm to 50nm.
[0096] Yet another optional plaque-dislodging ingredient in the
composition is
powdered cellulose (NPC) (available, for example, from JRS Pharma, Patterson,
NY).
Powdered cellulose is another ingredient that can provide very mild frictional
forces that
can enhance the removal plaque biofilm from surfaces. The particle size of
these
powdered cellulose particles and their amorphous content makes powdered
cellulose able
to enter and remove biofilm from tight spaces. Because powdered cellulose does
not
greatly expand in aqueous media, as well as because of its relatively low
cost, it is
possible to include larger concentrations of powdered cellulose than other
polymeric
plaque dislodging components in a formulation to help remove more plaque. This
allows
relatively large areas of the tooth surface to be wiped with each brush
stroke. Powdered
cellulose also does not have as much effect on the dentifrice viscosity as the
other
polymeric ingredients and hence it can be used at higher concentrations. Many
sources
of powdered cellulose are available with various particle sizes. The average
particle size
of the powdered cellulose used may be chosen to be from about 15nm to about
150 nm,
preferably from about 35nm to about 100nm, more preferably from about 50 m to
about
75 m. Preferred toothpaste embodiments can contain between about 0.2% and
about
25% of powdered cellulose, which can contribute to the rheological properties
of the
composition. The size of the ingredient matters in order for the ingredient to
be able to
enter the interproximal spaces.
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Fibers, fibrils, network-forming materials and comparison with commercial
Dentifrices
[0097] Embodiment compositions comprise water-insoluble discrete fibers and
fibrils
that form a 3-D network structure. Said fibers and fibrils are much larger (in
diameter
and length) than the size of the water-soluble macromolecular polymeric
thickeners used
to make commercial dentifrices. Examples of the fibers and fibrils source of
the inventive
compositions include microfibrillated cellulose and other network-forming
materials as
described elsewhere herein.
[0098] Embodiment fibers and fibrils have a diameter larger than 5nm, which
may be the
diameter of the smallest primary cellulose nanofibrils found in fibrillated
microfibrillated
or nano-fibrillated cellulose. In embodiment compositions, the fibers and
fibrils can be
much larger than 5 nm. The discrete fiber and fibrils of embodiments form an
entangled
and extended 3D network of flocs, bundles or domains. These entangled domains
can be
from 10 microns to more than 1000 microns in size when measured by laser
diffraction
at low concentration. These formed entangled domains may become interconnected
or
sintered and can form even larger extended structures as the concentration of
the fibers
and fibrils increases especially when activated or upon proper mixing. The
normally
become viscoclastic and arc difficult to breakdown by dilution or when
subjected to shear
forces. The fibers and fibrils may or may not be branched to form the
compositions of
the invention
[0099]The 3D network of the embodiment composition can delay or retard saliva-
induced
dilution and may hamper the microstructural network breakdown in the presence
of water
or saliva during brushing or cleaning as described herein. In contrast,
commercial
dentifrices are held together by short water-soluble polymer molecules (length
4-20 nm)
which when diluted by water or saliva during brushing they easily lose their
network
structure and form low viscosity slurry as it is known in the art. This slurry
may normally
include abrasive particles suspended in low viscosity aqueous solution which
may behave
as a Newtonian fluid.
Abrasives
[00100] In general, abrasives are added to dentifrices as a means of
preventing unsightly
stain build-up on teeth. The teeth absorb stains, from colored organic
substances in foods
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and drinks, on a daily basis. These stains become entrapped within
proteinaceous pellicle,
which is continuously formed in the mouth and deposited on teeth. Dentifrices
contain
mild abrasives, which are chosen to remove a thin layer of pellicle with much
of the stain
deposited each day. Some pellicle is left intentionally on the tooth surface
to prevent
abrasion to the underlying tooth. The pellicle layer gradually thickens over
time and the
degree of tooth staining increases until the layer of pellicle is about 101.t
in thickness. At
periodic semiannual visits to the dental office, the dental hygienist removes
tartar build-
up on teeth and polishes the teeth with an abrasive prophylaxis paste to
removes the
stained pellicle that formed since the previous visit. Thereby, the tooth
whiteness is
restored.
[00101] Teeth are composed of two types of mineral. The crown of the
tooth comprises a
hard exposed inorganic mineral, called enamel, and a softer inner organic root
portion,
known as dentin, which is encased in the enamel. The harder enamel layer ends
just
below the gum line and the root material below the enamel junction consists of
the softer
dentin. The gums recede with age exposing the softer dentin organic/mineral
from about
30 years of age. As a result, the dentin tooth organic/mineral below the gum
line becomes
exposed and due to its lesser hardness is especially subject to abrasive
damage during
brushing. The abrasives chosen for dentifrices may be chosen to be
sufficiently abrasive
to remove stained pellicle but not so generally abrasive as to damage tooth
enamel or
dentin. There are several factors affecting the abrasivity of toothpastes
including the
hardness of the abrasive material, the shape of the abrasive particles, the
size of the
abrasive particles and the concentration of abrasive in the dentifrice. A
useful summary
can be found in Pader M: Oral Hygiene Products and Practice (1988) 231-266.
[00102] The softer dentin is more adversely affected by the possible
abrasive effects of
dentifrices than is enamel. The standard method of determining dentifrice
abrasiveness
is using the Relative Dentin Abrasion (RDA) procedure, which is based on the
Radioactive Dentin Abrasion Method of Grabenstetter et al. (Grabenstetter RJ
et al., The
measurement of the abrasion of human teeth by dentifrice abrasives: a test
utilizing
radioactive teeth. J Dent Res 1957;37:1060-1068. This standard method compares
the
abrasivity of the dentifrices being evaluated, with that of a standard ADA
slurry (RDA =
100) To accomplish this, irradiated dentin samples are brushed with an aqueous
slurry
of the toothpaste in a standard brushing machine using fixed standard
conditions such as
the amount of toothpaste and dilution, number of brushing cycles, etc. The
amount of
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radioactive material found in the dentifrice slurry after a specified number
of brushing
cycles is then measured and compared with the results obtained using a
standard ADA
toothpaste slurry (which is considered to have an RDA of 100). A similar test,
the REA
procedure, is sometimes performed using tooth enamel (Bruce R Schemehorn et
al.,
Abrasion, polishing, and stain removal characteristics of various commercial
dentifrices.
J Clin Dent 2011;22(1) 11-18).
[00103] The ADA (American Dental Association) has generally recommended
that the
abrasivity of a toothpaste be no more than that needed to prevent the
excessive build-up
of stains on teeth. Of course, the amount of stain built up by different
individuals varies
widely. Hence, the optimum toothpaste abrasivity is different for each
individual and
depends on many factors such as genetics, diet, whether the individual is a
smoker or
regularly drinks strong tea etc. Accordingly, it is up to the consumer to
select the
toothpaste they find most suitable. While there are no strict rules concerning
abrasivity,
the following provides some guidelines regarding ranges for toothpaste
abrasivity.
[00104] A toothpaste with an RDA below about 50 is generally considered
to have very
low abrasivity. Such a dentifrice is particularly suitable for users whose
teeth have a low
tendency to stain. A toothpaste with an RDA abrasivity in the range of between
about
50 and about 150 is generally considered to have a moderate abrasivity. Such a
toothpaste would be satisfactory for most of the population with regard to
stain
prevention and potential damage to teeth. A toothpaste with an RDA abrasivity
of above
about 150 would generally be considered to exhibit a high abrasivity and would
only be
suitable for users with a high tendency to develop tooth staining, such as
smokers or
heavy tea drinkers. The FDA recommends a maximum upper limit on RDA of 200,
while
the ADA specifies an upper limit of 250. Accordingly, toothpastes with an RDA
above
250 would generally be considered to have an excessive abrasivity and be
potentially
damaging to teeth. Dentifrice compositions of embodiments of the invention
should
preferably have an RDA of between 30 and 200, more preferably between 50 and
150.
[00105] Depending on the type of dentifrice formulation and the desired
characteristics,
dentifrices can contain from about 5% to about 98% concentration of an
abrasive
ingredient. For example, the abrasive content of a powdered dentifrice could
range from
about 50% to about 98% (w/w). A toothpaste may have an abrasive content
between
about 10% and 65%, and the abrasive content of a tooth-gel can range from
about 5 to
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about 35%. For a tooth liquid (which has a viscosity intermediate between a
toothpaste
and a mouthwash), the concentration of abrasive might be from 5% to about 30%
w/w.
[00106]
Dentifrices that are used for professional cleaning in the dental
office, generally
have a higher acceptable abrasivity than dentifrices available for use at
home. This is
because the dentifrices for use at the dental office are designed for
infrequent use to
remove any stains which have built-up since the previous visit to the dentist.
While it is
generally undesirable for tooth mineral to be removed during a prophylactic
cleaning, it
is necessary to remove the pellicle layer with entrapped stain that has built
up since the
previous visit to the dentist.
[00107]
There are widely varying types of abrasives that can be included in
compositions
of embodiments of the invention. The following is a non-exclusive list of
abrasives that
would be effective in these toothpaste compositions: alumina, hydrated
alumina, silica,
aluminosilicates, calcium aluminosilicate, hydrated silica, calcium carbonate,
dicalcium
phosphate dihydrate, anhydrous dicalcium phosphate, tricalcium phosphate,
calcium
pyrophosphate, heat treated calcium pyrophosphate, untreated calcium
pyrophosphate,
calcium hydroxyapatite, insoluble sodium metaphosphate, calcium
polymetaphosphate,
magnesium carbonate, magnesium orthophosphate, magnesium trisilicate, titanium
dioxide, perlite, pumice, sodium bicarbonate, aluminum silicate and zirconium
silicate.
Preferred abrasives include hydrated silica (W. R. Grace Co.), known as
Sylodente, and
Zeodent, and dicalcium phosphate dihydrate and calcium carbonate.
[00108]
A wide choice and range of concentrations of abrasive can be used
dentifrices of the invention. Excessive toothpaste abrasivity is of course of
concern
regarding the potential scratching of tooth surfaces or thinning of the enamel
layer. There
are many types of abrasives which can be used, but a satisfactory choice might
be a
mildly abrasive dental grade of hydrated silica. It can be noted that the
abrasivity
provided by any amount or form of the cellulose itself that is contained in
embodiments
of the invention, is expected to be low.
[00109]
The term abrasives, as used herein, may or may not overlap in the
particle size
dimensions and other characteristics with the particles such as MCC that are
described
elsewhere herein. Abrasives are intended to remove stains from the surfaces of
teeth.
Such particles typically have hardness less than 3 on the Mohs Hardness Scale,
because
such hardness is sufficient to remove stain while not being so hard as to
damage tooth
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enamel or dentin. Their hardness may be greater than 2 on the Mohs Hardness
Scale.
Such particles typically have dimensions in the range of about 15 to about 30
microns
average diameter, or more generally 5 microns to 50 microns. Such particles
may be
spherical or not greatly elongated in shape (elongated by a factor of not more
than 2), or
may be irregular. In comparison with the particles such as MCC, the abrasive
particles
may be smaller than the particles such as MCC, and their shape may be closer
to spherical
(such as elongated by a factor of not more than 2) than are the shapes of the
particles
such as MCC. Examples of the composition of such abrasive particles include:
amorphous silica such as that made by W. R. Grace and Company others (e.g.
Zeodent
113, DeWolf Chemical, Warwick, RI); calcium carbonate (CaCO3); calcium
phosphates
and zeolites (which are microporous aluminosilicate minerals). A composition
of
embodiments of the invention can contain silica, typically amorphous hydrated
silica
having a hardness less than 3 on the Mohs hardness scale This would be mostly
for stain
removal, while still being soft enough so as not to erode enamel or dentin.
Such material
is available from W. R. Grace and Co. as SYLODENTOD. Among the many known
forms
of silica, silica used herein may be dental grade silica, which provides
appropriate
hardness and particle size range. Alternatively, the hardness could be harder.
[00110]
It is desirable that the abrasive chosen should be compatible with the
other
ingredients in the dentifrice especially the source of fluoride ingredient.
There are
several abrasives that cannot be used when sodium fluoride or stannous
fluoride are
present because those abrasives would cause the precipitation and inactivation
of the
fluoride ions during storage. The following abrasives are compatible with
sodium
fluoride:
silica, hydrated silica, heat treated calcium pyrophosphate, sodium
metaphosphate, titanium dioxide, perlite and sodium bicarbonate. The following
abrasives are compatible with stannous fluoride: silica, hydrated silica, heat
treated
dicalcium phosphate, sodium metaphosphate, titanium dioxide, perlite. In the
event that
one of these fluoride incompatible abrasives is desired for the composition, a
stable
fluoride-containing composition can usually generally be formulated with
sodium mono-
fluorophosphate.
[00111]
The concentration of such abrasive particles can be in the ranges
defined herein
for the prototype formulation (irrespective of other ingredient concentrations
in the
prototype formulation).
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[00112] Herein, it has been found that the presence and concentration
of the abrasive
particles has an effect on the rheology of the composition. It is believed
that the various
types of particles described herein (both abrasives and particles that are MCC
or similar
substances) are incorporated in and entangled in the network formed by the
Minute
Fibrils. This raises questions about the relative function of abrasive
particles and the
particles that are MCC or similar materials. It is possible that their roles
in cleaning
overlap and they both have effects on the rheology of the composition. This
may allow
for using mixtures of abrasive silica and MCC to tailor cleaning and to reduce
erosion of
enamel and dentin. The effect on rheology can be quantified, for example, by
measurement of G' using a rheometer. Although abrasive silica has been used in
experiments, it is believed that other similar solid particles such as calcium
carbonate
could similarly be used. It is even possible that particles of abrasive could
entirely
substitute for MCC. In the present work, it has been found experimentally that
particles
of substances such as abrasives can be entangled in network and this can have
a profound
effect on rheology and can even increase viscosity or G' by as much as factor
of 10 or
even more.
SuperAbsorbent Polymer
[00113] In embodiments of the invention, a composition can include a
superabsorbent
polymer (SAP). Superabsorbent polymers have the ability to absorb very large
amounts
of water compared to their dry mass, for example up to 1000g of water per gram
of
polymer.
[00114] Information on SAP, and options for SAP, such as particulate
SAP, can be found
in patent application US Serial Number 16/461,536, filed May 16, 2019, for
example at
0029-53. Superabsorbent polymers are reviewed in Mignon A et al:
Superabsorbent
polymers: A review on the characteristics and applications of synthetic,
polysaccharide-
based semi-synthetic and smart derivatives. European Polymer Journal 2019;
117:165-
178. Superabsorbent polymers are also reviewed in: Superabsorbent Polymer
Materials:
A Review. Iranian Polymer Journal, June, 2008. Superabsorbent polymers may be
either
synthetic or naturally-occurring.
[00115] A common chemical category of SAP polymers is polyacrylate-
acrylic acid
polymers. For example, a useful synthetic Super Absorbent Polymer is typically
a
copolymerization of acrylic acid with sodium, potassium or ammonium salts, or
surface
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cross-linked polyacrylic acid. A list of SAPs that can used without limitation
is given in
our SAP patent application US20200270551, U.S. Serial Number 16/461,536. See
also
Superabsorbent Hydrogels That Are Robust and Highly Stretchable, by B.H.
Cipriano et
al, Macromolecules 2014, 47, 4445-4452.
[00116] However, any SAP chemistry that is safe for dental or oral use
can be considered.
Embodiments of the invention are not limited to polyacrylate-acrylic acid
polymers or
their derivatives.
[00117] Embodiments of the invention may include natural SAPs for
example
polysaccharide-based SAPs. In regard to naturally occurring SAP, an example of
a
natural superabsorbent absorbent polymer is soluble fibrous ingredient
comprises
psyllium polysaccharide. This polysaccharide is present in natural plantago
ovarta, as
well as in psyllium husks, seeds and leaves. This polysaccharide source, which
is mostly
composed of inulin, is a water-soluble fructan fiber with a beta-(2-1)
glucoside linkage.
This mucilaginous material expands in water and increases its viscosity. It
helps to
provide more structure and enhances plaque biofilm removal. Psyllium seems
better able
to retain moisture than synthetic SAPS without the need for cross-linking.
Without being
bound by this mechanism, we believe that its advantageous characteristics are
probably
associated with the ring structures in psyllium. Water molecules can fit into
the ring
structures and are held by hydrogen bonding by the hydroxyl groups on the ring
Other
potentially suitable natural sources of soluble super absorbent mucilage,
which expand
in aqueous media, are beta-glucans from oats, oat bran, flaxseed, pectin and
gums found
in berries, seeds, citrus peel or other fruit sources. Water-absorbing
polysaccharides may
preferably be chosen so that they are not lubricating, as discussed elsewhere
herein.
[00118] The particle size of the dry SAP particles can range from 2 to
63 microns or from
2 to 106 microns more preferably from about 5um to about 75um, or from 2 to
150
microns or larger, and can include particles up to 800 microns The SAP
particles may
include small particle size versions such as carbopols or carbomers (about 2
to 7 um), as
well as larger particles such as those used in hygiene pads or diapers or
similar
applications (2 um up to 800 um). The particle sizes of SAP and NSAP may be
chosen
so that when the particles are in the swollen state the particles are no
larger than about
200 m. Other sizes are also possible.
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[00119] Synthetic superabsorbent polymers may be made from polymeric
water-soluble
polymers that are surface cross linked to allow water to be absorbed through
the lightly
cross-linked matrix around the absorbing polymer. The polymer swells and forms
a gel,
thereby entrapping absorbed water. A useful property of such a polymer is that
the
particles of cross-linked protected polymer gel do not merge, stick together
or lose their
individual particulate identity. r[he result is the polymers have a high
absorption capacity
for water within its matrix structure, which can allow it to absorb up to 1000
times as
much water as its dry weight. Non-crosslinked polymers are less desirable for
this
purpose because they are not protected from merging. The SAP can be surface
crosslinked or non-surface crosslinked or highly bulk cross-linked or a
mixture of the
various forms.
[00120] The SAP polymer is envisioned to be in the form of discrete
particles that tend to
retain their identity as separate particles even after swelling. It is
believed to be preferable
to use SAP particles that are surface crosslinked or highly bulk cross-linked
Such
particles avoid coalescing with each other after swelling. The SAP particles
may be able,
even when mixed or incorporated in the described composition, to preserve
their integrity
as discrete particles rather than joining other SAP particles to form a soft
mass or
expanded gel domains. The CRC (Centrifuge Retention Capacity) values may be
from
50 to 500 g/g in pure water or from 15 to 50 g/g in saline solution. The CRC
value for a
cross-linked SAP is expected to be smaller than the CRC value for a non-cross-
linked
version of the same substance. The CRC value for a cross-linked SAP is
indicative of the
extent of cross-linking, with larger amounts of cross-linking being associated
with
smaller CRC value.
[00121] It is believed (although it is not wished to be limited to this
explanation) that
particles of SAP that are Surface Cross-linked or highly bulk cross-linked are
more likely
to retain their shape. It is believed, although it is not wished to be limited
to this
explanation, that desirably the SAP particles should not be ground or milled
after Surface
Cross-Linking, so that not more than 10% of the bulk polymerized SAP is
exposed, or
10% of the total surface of the SAP, or 10% of the particles. The majority of
the SAP
particles may be provided having outer surfaces that are intact after the
surface cross-
linking. The surface crosslinked SAP also increases the elastic properties
(G') of the
composition, compared to compositions containing non-surface-crosslinked SAP.
It is
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believed, although not confirmed, that SAPs may limit breakdown of the network
and
may retard the effect of dilution due to water or saliva as described
elsewhere herein.
[00122] It is believed, although it is not wished to be limited to this
explanation, that
desirably the SAP particles should not be ground or milled after Surface Cross-
Linking,
so that not more than 10% of the bulk polymerized SAP is exposed, or 10% of
the total
surface of the SAP, or 10% of the particles. The majority of the SAP particles
may be
provided having outer surfaces that are intact after the surface cross-
linking. It is possible
that the particles of SAP, or the majority of them, may have irregular shapes.
Other SAP
particle shapes may be used including spherical or irregular without
limitation. The
density of bulk and surface cross-linking density can be tailored as desired
without
limitation. Further information is available in co-pending commonly assigned
patent
application U. S . Serial Number 16/461,536.
[00123] A desirable criterion regarding Surface Cross-Linked (SCL) or
otherwise
desirable particulate SAP can be that if the particles are contacted against
each other
under load, the particles do not join or merge with each other. Particles of
SAP that are
surface cross-linked or highly bulk cross-linked may have CRC values that are
smaller
than the corresponding values for the same SAP material that is not surface
cross-linked.
Thus, the CRC value may be a representation of how much cross-linking has
occurred.
The outer surface of the SCL particles may desirably be thick enough to result
in a CRC
value in saline (0.9% concentration of NaCl, i.e., physiological saline
solution) less than
32 g/g, preferably less than 28 g/g. The particles of SAP may be entangled in
the fibrous
network.
[00124] It is believed that when MFC and superabsorbent polymers
together are combined
and exposed to water, they expand and together play a role in helping to
dislodge plaque
biofilm and displace it from tooth surfaces. SAP particles may be incorporated
within the
fibrillated network, as evidenced by microscopic examination The resulting
entangled
network forms a viscoelastic fluid which helps to transfer the forces of
brushing to the
biofilm on the tooth surface, hence effecting removal of the biofilm. In
addition, the
resulting rheology of the embodiment composition is such as to limit the
formation of a
depletion layer at tooth surface, which in turn ensures more direct contact
between the
dentifrice ingredients and biofilm. It is believed that the SAP enhances the
elastic
properties (G') of embodiment compositions, such that the elastic component
forces the
composition to make contact with biofilm under the action of normal force
applied by
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the toothbrush. During translational motion during brushing, shear forces are
created to
remove adhering biofilms from teeth. However, we do not wish to be bound by
any
particular explanation.
Humectant or water retention agent
[00125] Water activity also describes the chemical activity of the
water in the toothpaste,
as it relates to physical, chemical and microbiological characteristics of an
aqueous
solution For example, because bacteria and fungi need moisture to survive, a
low water
activity will prevent bacterial and fungal growth in the toothpaste. Most
bacteria do not
grow when the water activity is less than about 0.8. Other organisms cannot
grow if the
water activity is less than 0.6. It should be noted that bacteria and other
organisms can
still be viable when the water activity is low even if they do not grow. Of
course, growth
and viability of organism is also affected by the presence of other
ingredients in the
formulation, such as preservatives. Replacement of water with humectants
reduces the
water activity and generally improves the smoothness and consistency of a
toothpaste.
Some humectants also generally improves the smoothness and consistency of a
toothpaste. Humectant ingredients also are reported to reduce attachment of
plaque
biofilm to tooth surfaces.
[00126] The water activity (Wa) of a composition is the ratio between
the vapor pressure
of the composition itself, when in equilibrium with the surrounding air media,
and the
vapor pressure of pure water under identical conditions. Water activity is
measured by
determining the equilibrium vapor pressure above the toothpaste in an enclosed
container
at the chosen temperature. The water vapor pressure is then divided by the
vapor pressure
of pure water at the same temperature and Water activity is expressed as a
number
between 0 and 1. This is described in US patent 7,135,163. Ideally, for
toothpaste, the
water activity should be less than about 60% although another useful target
can be less
than 70%. Preferably, the water activity of toothpaste embodiments should be
less than
0.78, more preferably less than 0.75 and most preferably less than 0.70.
[00127] Preferable humectants include glycerin, 1,3 propylene glycol,
1,2 propylene
glycol and sorbitol. Xylitol and erythritol are other useful humectants and
may have some
additional benefits perhaps by preventing plaque attachment or by favoring
less
cariogenic bacteria in the mouth. Compositions of the invention may include
one or more
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humectants selected from the following: glycerin, sorbitol (available as
sorbitol 70%),
xylitol, erythritol, 1,3 propylene glycol, 1,2 propylene glycol, dipropylene
glycol,
ethylene glycol, polyethylene glycols with from about 5 to 12 repeating
ethylene glycol
units, and higher polypropylene glycols, and some other sugar alcohols.
[00128] In embodiments of the invention, in order to lower water
activity down to 0.75 or
lower, the humectant may be glycerol, propane di ol or sorbitol at a
concentration of 30%,
40% or even 50% of the composition, preferably in the range of 35% to 45%. It
is
possible to use a combination of these hutnectants, and the concentration can
be the total
of the concentrations of the individual humectants. It can be noted that
xylitol and
etythritol precipitate at concentrations above around 30%.
[00129] Inert fillers such as microcrystalline celluloses might have an
effect of reducing
water content and helping to control the water activity. Salts that can be
added include
mono, di- and trisodium orthophosphate, monoammonium, diammonium and
triammonium phosphate and monopotassium, dipotassium and tripotassium
phosphate
salts. The pH range may preferably be 3.5 to 9.5.
[00130] Humectant-water mixtures may be used to make the compositions
of
embodiments of the invention, as described elsewhere herein.
Surfactants or foaming agent
[00131] In embodiments of the invention, the composition can include a
surfactant or a
mixture of surfactants.
[00132] The surfactant may help in the removal of plaque. A significant
purpose of
surfactants is to create some foam during brushing. Foaminess is a sensory
attribute that
users expect and prefer, because they associate it with effective cleaning.
Accordingly,
in embodiments, the composition can include a surfactant that can produce some
foam
upon being agitated, as long as the type and concentration of the surface does
not
negatively impact the desirable rheological or friction properties as
described elsewhere
herein.
[00133] Surfactants may also have benefits as emulsifiers, which can be
used to disperse
water-insoluble ingredients such as flavor oils into the composition. It is
possible that in
the absence of a surfactant, during storage, such water-insoluble oils might
undesirably
separate from the bulk aqueous phase.
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[00134] Formulation embodiments of these compositions may include one
or more
surfactants in concentrations between about 0.1% and 2.0%, preferably between
about
0.25% and 1.5%, and most preferably from about 0.4 and about 1.2%. Preferred
ingredients in compositions of the invention are one or more surfactants which
are
present in a concentration not to exceed about 2.5% and preferably in a
concentration
between 0.2% and 1.5%. Higher concentrations can be irritating while
concentrations
that are too low will not create sufficient foam.
[00135] Suitable surfactants include almost any non-toxic, non-
irritating surfactant.
Commonly used surfactants that can be used in toothpastes or other oral rinses
are sodium
laureth sulfate and cocamidopropyl betaine. Other possible surfactants include
for
example sodium lauryl sulfate (SLS) or sodium dodecyl sulfate (SDS) which is
commonly used in commercial toothpastes.
[00136] In general, a surfactant in an embodiment of the invention can
be any type of
surfactant, including for example, anionic, cationic, or amphoteric
surfactants. Most
preferred surfactants are either anionic or amphoteric surfactants and
mixtures thereof. It
is useful to specify the degree of foaminess and the type of foam so that the
composition
can remain effective in removing plaque biofilms and calcium deposits during
application.
[00137] In regard to anionic surfactants, examples of suitable anionic
surfactants are
water-soluble salts of alkyl sulfates with between 8 and 18 carbons in the
alkyl chain.
[00138] Preferable anionic surfactants for use in toothpaste of this
invention include
sodium lauryl sulfate (SLS), which is also known as sodium dodecyl sulfate
(SDS).
Another suitable anionic surfactant is sodium lauroyl sarcosinate. Another
group of high
foaming anionic surfactants is sodium salts of hydroxyalkyl sulfates, for
example sodium
2-hydroxyteradecyl sulfate and sodium 2-hydroxydodecyl sulfates. These
surfactants are
known to avoid the "orange juice effect" experienced with many other anionic
surfactants. The orange juice effect results in a seriously adverse flavor
when orange
juice is imbibed after toothbrushing was performed using surfactant-containing
toothpaste. Among other useful anionic surfactants are sodium N-methyl
taurate, and
sodium salts of sulfonated monoglycerides. A most preferred alkyl sulfate is
sodium
lauryl sulfates. Another group of useful anionic surfactants include water
salts oflauroyl ,
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cocyl, myristoyl and palmityl and steroyl sarcosinates. Particularly preferred
is sodium
lauroyl sarcosinate.
[00139] Examples of suitable anionic surfactants are the water-soluble
salts of alkyl
sulfates with between 8 and 18 carbons in the alkyl chain. A most preferred
alkyl sulfate
is sodium lauryl sulfate. Another group of useful anionic surfactants include
water-
soluble salts of lauroyl, cocyl, myristoyl, palmityl and steroyl sarcosinates.
Of these,
sodium lauroyl sarcosinate is preferred. A combination of sodium lauryl
sulfate and
sodium lauroyl sarcosinate provides a synergistically higher amount of foam
than when
either is used alone. Another anionic surfactant which is suitable in these
dentifrice
embodiments is sodium methyl cocoyl taurate. Similarly, sodium lauryl
sulfoacetate and
sodium lauroyl isoethionate can be used. Sodium laureth carboxylate is a
somewhat
lower foaming but acceptable surfactant. Another group of high foaming anionic
surfactants are sodium salts of hydroxyalkyl sulfates, for example sodium 2-
hydroxytera decyl sulfate and sodium 2-hydroxydodecyl sulfate Among other
useful
anionic surfactants are sodium N-methyl taurate, the water-soluble salts of
sulfonated
fatty acid mono-glycerides having 8-18 carbons in the fatty acid chain are
also effective,
especially is sodium coconut monoglyceride sulfonate.
[00140] In regard to amphoteric surfactants, a preferred amphoteric
surfactant is
cocamidopropyl betaine. Examples of amphoteric surfactants which can be
utilized in
embodiments of these dentifrices include alkyl betaines such as lauryl,
myristyl, palmityl
and cetyl betaine. Also useful are the amidobetaines including cocamidopropyl
betaine,
cocamidoethyl betaine and lauramidopropyl betaine. Cocamidopropyl betaine is
especially preferred when used alone or in combination with an anionic
surfactant such
as sodium lauryl sulfate. Amphoterics are often less irritating than other
surfactants and
sometimes even reduce the irritation potential of other ingredients. Amine
oxide
surfactants, either alone in combination with betaine surfactants, can be used
to make the
inventive compositions as they may impart some antimicrobial properties.
[00141] In regard to nonionic surfactants, a suitable group of nonionic
surfactants includes
those known as the poloxamers (block co-polymers of ethylene and propylene
oxide),
polysorbates and sucrose or glucose esters. Nonionic surfactants also are
especially
useful as emulsifiers, for example to disperse flavor oils and other water-
insoluble
ingredients into the dentifrice. However, nonionic surfactants tend not to
deliver as high
a foam as is achieved with anionic surfactants and amphoteric surfactants.
Nonionic
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surfactants may be utilized in combination with anionic or amphoteric
surfactants to
stabilize the foam.
[00142] Cationic surfactants, especially those which have antimicrobial
properties, are not
necessarily desirable for compositions of these embodiments, because such
surfactants
tend to be significantly more irritating and cytotoxic to the oral mucosa than
other
surfactants. Therefore, if they are used, the concentrations may be limited to
a small
concentration, for example, generally less than 0.3%. A further concern with
cationic
antimicrobials is their potential to promote the development of antibiotic and
antimicrobial resistant strains of bacteria as discussed previously concerning
toothpaste
antimicrobials. Cationic surfactants also have other undesirable properties,
such as
increasing tooth staining, and incompatibility with many other potentially
useful
ingredients such as anionic surfactants and anionic polymers (e.g., CMC).
Cationic
surfactants also form inactive salts with saccharin and, when used with high
specific
surface area abrasives, are adsorbed and thereby inactivated
[00143] Where cationic surfactants can sometimes be used is to provide
anti-microbial
activity to the dentifrice. However, cationic surfactants are often
incompatible with other
ingredients in some formulation. For such reasons, cationic surfactants may be
less
preferred for cleaning teeth. However, for various reasons cationic
surfactants might be
included in suitable concentrations. For example, cationic surfactants are
routinely used
in "Scope mouth rinse" made by Procter & Gamble. Suitable cationic
surfactants, which
are also antimicrobial, include benzalkonium chloride, benzethonium chloride,
methyl
benzethonium chloride, cetyl pyridinium chloride and tretradecylpyridinium
chloride.
[00144] A specific surfactant ingredient that can be used is LAE
(Lauryl Alginate Ester)
hydrochloride or other salts. LAE is a natural cationic surfactant and is a
natural
preservative, and it has good attributes for retarding biofilm formation. For
example, we
have found that a concentration of 0.1% to 1% of LAE, or 0.5% to 1%, in
combination
with other ingredients of the inventive tooth cleaner, can also produce foam
and promote
cleaning. LAE is a cationic surfactant and it breaks down to arginine (which
is an amino
acid) and lauryl acid (which is a fatty acid) both of which are common in food
and are
safe. LAE seems to lower the surface tension of its composition and may also
have a
propensity to absorb on the surface of teeth giving after-brushing more
persistent effect
that may delay or retard biofilm formation. LAE has good ability to form foam
(which is
desirable in toothpaste), and also is a preservative and has some
antimicrobial effect. It
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is considered a cationic surfactant and can replace other surfactant options
for the
formulation. Because of its arginine moieties, LAE may protect against tooth
sensitivity.
[00145] It should be noted that the presence of surfactants is not
essential to the
performance of embodiments of these compositions. However, we have found that
the
cleaning action is often improved by the presence of surfactants.
[00146] Foaming agents are a subset of surfactants, and constitute an
important ingredient
in toothpastes. Consumers perceive toothpastes as less effective at cleaning
if the foam
is insufficient. However, the concentration of foaming agent added to the
toothpaste
formulation should not be excessive. Excessive foaming agent adversely affects
flavor
and mouth feel. Furthermore, some consumers are sensitive to surfactants and
suffer
from mouth sores when too much foaming agent is present. A widely used foaming
agent
is sodium lauryl sulfate. It is possible that sodium lauryl sulfate is
acceptable and less
risky than choosing other possible surfactants. On the other hand, it might be
possible to
identify a more natural or naturally-derived surfactant, though this could
take
considerable effort. For example, it is possible that a concentration of from
0.5% to 0.8%
of sodium lauryl sulfate would prove satisfactory.
Thickeners and Rheology Modifiers in general
[00147] In addition to inclusion of minute fibrils, fibrillated
materials or network-forming
ingredients, one of the mechanisms by which the inventive composition promotes
dislodgement and removal of plaque biofilm, is by achieving an appropriate
rheology of
the composition as detailed elsewhere herein. In toothpastes in general, it is
sometimes
desirable to incorporate thickeners or rheology modifiers for aesthetic or
performance
reasons. An increase in viscosity or G' may be desirable to prevent sagging of
the
toothpaste ribbon and to help stand-up when applied to the toothbrush. Such
also may
help prevent syneresis and may give a smoother feel to the composition.
Thickeners may
also be used in toothpastes to help suspend undissolved ingredients such as
abrasives.
Additionally, as noted regarding the composition's plaque dislodging
ingredients,
increasing the dentifrice's viscosity and tailoring its rheological parameters
can help the
transfer of brushing forces to biofilm being removed. However, in embodiments
of the
invention, it is found that there are both advantages and disadvantages for
thickeners and
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rheology modifiers. The disadvantage can be lessening the contact of the
fibers and fibrils
and various types of particles with the biofilm at the surface to be cleaned.
Inorganic thickeners
[00148] One commonly used group of thickening agents are the inorganic
thickeners
frequently referred to as thickening silicas. These silicas are distinct from
abrasive
silicas, which are sometimes referred to as cleaning silicas. Both types of
silicas are
sometimes referred to as "hydrated silica" or occasionally even just as
"silica." The
primary differences between thickening and abrasive silicas are in their
specific surface
areas, absorptive capacities and abrasivities. Thus, thickening silicas have
larger specific
surface areas and higher liquid absorptive capacities but are essentially non-
abrasive,
whereas abrasive silicas have smaller surface areas and lower absorptive
capacities but
deliver much higher abrasivities. As a result, abrasive silicas may affect the
viscosity
and other rheological properties, not to the same degree as thickening
silicas. If an
inorganic thickener is used, preferred inorganic thickeners include hydrated
silicas,
amorphous silicas, pyrogenic silicas, colloidal silicas, fumed silicas, and
silica gels used
at concentrations between about 1% and 10%. When added to aqueous media,
silicas
thicken through hydration with moisture in the composition forming a hydrated
silica
structure throughout the dentifrice. In addition to increasing the
toothpaste's viscosity,
another use for thickening silicas is to improve the mouthfeel of the
composition.
[00149] As examples of inorganic thickeners, embodiments of the
invention may
comprise from 0% to about 10% concentration of silicas, such as Zeodent 165.
These
silicas absorb water and form chemical hydrates with silica. These materials
form links
and thicken aqueous compositions. It is also possible to use inorganic
thickeners such as
laponite and other clays.
[00150] In toothpastes in general the concentration of such inorganic
thickeners, if
present, could be in the range of 0.5% to about 10%. However, in work relating
to
embodiments of the invention, it has been found that it is preferable that the
concentration
of inorganic thickeners be limited to no more than 0.5% to 4% of the
composition.
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Polymeric thickeners
[00151]
Polymeric thickeners, which are common in conventional toothpastes, can
be
used in embodiments of dentifrice formulations discussed herein. For example,
organic
polymers are useful in adjusting the viscosity of dentifrices and liquid
compositions.
Additionally, they can be helpful for smoothing the dentifrice and for
preventing
syneresis (separation). The term polymeric thickeners as used herein does not
refer to the
Minute Fibrils or fibers.
[00152]
Polymeric thickeners may be long chain polymers having hydrophilic
groups
spaced along the polymer chains and usually having high molecular weights for
example
from 2,000 to about 6 million Daltons. The hydrophilic groups may be nonionic,
anionic
or cationic. Non-exclusive
examples of useful thickening polymers include
polysaccharide gums, such as cellulose derivatives, including sodium
carboxymethyl
cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl
cellulose.
Other polysaccharides include guar gum, xanthan gum, carrageenan gum,
tragacanth
gum, and alginate salts of sodium potassium or ammonia, an alkali metal or
ammonium
salt of a polyacrylic acid, sodium carboxymethyl cellulose, hydroxymethyl
cellulose,
hydroxyethyl cellulose and hydroxypropyl cellulose, other hydropolymers based
on
cellulose derivatives, an alkali metal alginate salt or an ammonium alginate
salt. Other
such organic thickeners include polyvinylpyrroli done, polyethylene oxide,
polyacrylamide and its derivatives, which are used in some conventional
toothpastes at
concentrations between about 0.5 to about 10%, such as to improve the
formulation
texture and aesthetics.
Fluoride additive
[00153]
Fluoridating agents represent another optional dentifrice ingredient,
which may
be present in embodiments of these dentifrices. Meta-analysis of multiple
clinical studies
has confirmed a dose-dependent performance of fluoride toothpastes in
preventing caries
(Walsh T et al., A Fluoride Toothpastes of Different Concentrations for
Preventing
Dental Caries. [Cochrane Database of Systematic Reviews 2019, Issue 3. Art.
No.:
CD007868. DOI: 10.1002/14651858 .CD007868.pub3].
[00154]
In the United States, the fluoride content of Over-The-Counter anti-
caries
toothpastes is regulated by the FDA. The FDA has published Monograph (Code of
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Federal Regulations; Title 21, Volume 5; Revised as of April 1st, 2019;
21CFR355),
which provides the range of fluoride concentrations permissible in
toothpastes, the
maximum allowable amount of fluoride in a single container of toothpaste, the
permissible types of fluoride for use in dentifrices, and rules concerning pre-
testing of
fluoride availability and performance versus clinically proven effective
fluoride
toothpaste standards. The regulations also cover minimum concentrations of
active
fluoride which must be present during the labeled shelf life of the
toothpaste. The
Monograph also lays out package label requirements. Other countries have
similar
regulations although the details may differ significantly.
[00155] Embodiments of compositions herein described can optionally
include a fluoride
compound that can deliver active fluoride ions to the teeth. Three sources of
fluoride,
i.e., sodium fluoride (NaF), stannous fluoride (SnF2) and sodium mono-
fluorophosphate
(Na2P03F), are permitted in the USA under the FDA Monograph. In addition to
caries
prevention, these compounds can strengthen tooth enamel and reduce erosion of
teeth by
acidic foods and drinks.
[00156] The FDA mandates testing requirements for fluoride availability
and
performance compared to clinically proven standards available through the USP
(United
States Pharmacopeia). It should be noted that amine fluorides are not a
permissible
source of fluoride in the USA, but they are approved in many other countries.
For such
other countries, embodiments of these compositions can include amine fluoride
toothpaste.
[00157] In an embodiment of the invention, the composition may include
a fluoride
compound that is suitable to deliver active fluoride ions to the teeth. Such
fluoride
compound may be or may include sodium fluoride (NaF) or stannous fluoride
(SnF2)
system or sodium monofluorophophate (Na2P03F) or other acceptable sources of
fluoride without limitation. Such compounds are widely used in toothpastes and
other
dentifrices to strengthen tooth enamel. It is believed that such compounds
convert the
calcium mineral apatite into some form of fluorapatite. It is further believed
that the
resulting tooth enamel is more resistant to bacteria-generated acid attacks
The effective
bioavailable concentration of fluoride should be equivalent to that of current
commercial
toothpastes. Such fluoride compound may be or may include sodium fluoride
(NaF) or
stannous fluoride (SnF2) or sodium monofluorophophate (Na2P03F). Such
compounds
are widely used in toothpastes and other dentifrices to strengthen tooth
enamel. It is
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believed that such compounds convert the calcium mineral apatite into
fluorapatite. It is
further believed that the resulting tooth enamel is more resistant to bacteria-
generated
acid attacks. The effective bioavailable concentration of fluoride may be
chosen to be
equivalent to current commercial toothpastes.
[00158] In one of the commercially available toothpastes, the
concentration of sodium
fluoride is 0.24% by weight. In Commercial Toothpaste R, the concentration of
stannous
fluoride is 0.454% (which corresponds to a 0.15% w/v concentration of active
fluoride
ion). In embodiments of the invention, a fluoride concentration similar to or
possibly
higher than these concentrations can be used.
[00159] It can be noted that the presence of active fluoride ions was
not a consideration
for applications such as the cleaning of endoscope channels (described in
US10266793).
Although a toothpaste could be made without fluoride, most current toothpastes
include
fluoride as recommended by the American Dental Association. It is preferred to
include
water-soluble compounds, which deliver free fluoride ions to the teeth.
Dentifrices that
deliver appropriate amounts of free fluoride ions have been proven to
significantly reduce
the incidence of caries in users.
[00160] When included in dentifrices, preferred fluoride compounds are
sodium fluoride
(NaF), stannous fluoride (SnF2), or sodium mono-fluorophosphate (Na2P03F).
Such
compounds are widely used in toothpastes and other dentifrices to prevent
caries and
strengthen tooth enamel. All three of these fluoride ingredients are approved
by the FDA
as proven Safe and Effective for use as an anti-caries agent in dentifrices.
Less preferred
but acceptable fluoride compounds for use in dentifrices of the invention are
amine
fluorides. While amine fluorides are reported to deliver more fluoride to
tooth mineral
than other fluoride compounds, amine fluorides are not are not approved for
inclusion in
dentifrices by the FDA in the USA.
[00161] There are several mechanisms by which fluoride prevents caries:
(1) Fluoride
ions promote remineralization of tooth enamel using calcium and phosphate ions
from
saliva; (2) Fluoride ions react with calcium hydroxyapatite in tooth enamel
producing a
less water-soluble calcium fluoro-apatite and thereby reduce enamel
demineralization
due to acids from cariogenic bacteria; (3) Fluoride has an inhibitory effect
on the growth
of oral bacteria, thereby decreasing acid release by cariogenic bacteria.
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[00162]
Each fluoride-releasing compound has different characteristics, which
affect the
choice of fluoride depending on the composition of the dentifrice. Sodium
fluoride
completely releases essentially all of its fluoride ions to the saliva during
brushing for
maximum effectiveness. However, fluoride can be precipitated and deactivated
in the
presence of divalent and some other ions or by some types of abrasives. Hence
sodium
fluoride cannot be used in compositions conducive to its deactivation.
[00163]
The fluoride in sodium mono-fluorophosphate is not present in the form
of free
soluble fluoride ions. Hence, the fluoride in sodium mono-fluorophosphate is
"protected" from reaction with divalent and other incompatible ingredients.
Therefore,
sodium mono fluorophosphate is the fluoride source of choice for dentifrices
containing
fluoride-incompatible ingredients. Studies generally indicate that sodium mono-
fluorophosphate is slightly less effective than sodium fluoride in preventing
caries
because it takes time for free fluoride ions to be released from sodium mono-
fluoroph osp hate during brushing
[00164]
Stannous fluoride has some performance advantages over other fluoride
sources.
Firstly, stannous ions react with tooth enamel and strengthens it, making it
more resistant
to acid attack. Stannous fluoride is also an effective antimicrobial agent,
which decreases
plaque biofilm build-up on teeth and reduces gingivitis. Furthermore, stannous
fluoride
is effective in reducing supragingival gingivitis. Another benefit of stannous
fluoride is
its ability to block dentinal tubules, which lead to the nerves in teeth. As a
result,
stannous fluoride is effective in preventing tooth sensitivity. As a
disadvantage, stannous
fluoride is somewhat less stable than sodium fluoride in dentifrices. Hence
stannous
fluoride-containing dentifrices gradually lose some of their effectiveness on
storage.
Additionally, stannous ions cause stain build-up on teeth. Furthermore,
stannous fluoride
imparts an adverse flavor, which is difficult to cover.
[00165]
Amine fluorides tend to deliver greater amounts of fluoride to the
surface of teeth
and hence should be more effective in preventing dental caries. Examples of
amine
fluorides include: Ammonium monofluorophosphate; Ammonium fluoride; Hexadecyl
ammonium fluoride;
3 -(N-h exadecyl -N-2-hydroxyethyl -ammoni o)propylbi s(2-
hydroxyethyl) ammonium dihydrofluoride; Ammonium hexafluorosilicate. However
as
noted above, amine fluorides are not approved by the FDA in the USA but are
used in
some other countries.
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[00166] Dentifrices of the invention in general contain between about
0.05% to about 1%
by weight of active fluorine. Dentifrices for regular twice daily home use
should contain
between about 0.08% to about 0.25% soluble fluoride compound. Prophylaxis
pastes,
used in the dental office, should contain from about 0.2% to about 1%
fluoride. It can
be noted that fibers and other components might skew what amount of fluoride
is
biologically available. For the USA, the permitted contents for fluoride
toothpaste are
identified in Table 1C.
Table 1C
Summary of FDA Monograph regulations for fluoride in OTC Dentifrices
Fresh Aged
Type of fluoride Total Soluble F Soluble F
compound
ppm F ppm ion ppm ion
Sodium fluoride - 1100 850-1150 >650 0.188
Stannous fluoride - 1100 850-1150 >700* 0.351
Sodium MFP -Either 1100 850-1150 >884 0.654-0.884
or
-Or 1500 1500 >1275 1.
153%NaMFP
* >290ppm when heat treated calcium pyrophosphate abrasive is used
Buffer salts
[00167] In embodiments of the invention, buffer salts such as mono, di
and trisodium
orthophosphate, monoammonium, diammonium and triammonium phosphate, and
monopotassium, dipotassium and tripotassium phosphate salts can be included.
Phosphate salts are not generally suitable as buffers for stannous fluoride
toothpastes.
These salts can serve to maintain the pH of the composition close to a desired
value. The
desired pH range for toothpastes with these embodiments is from about 3.5 to
about 9.5
depending on the various ingredients in the toothpaste. For example, stannous
fluoride
needs a toothpaste in the pH range between about 4 to about 5.5. Sodium
fluoride and
sodium monofluorophosphate can be used at higher pH values.
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Adjuvants
[00168] In embodiments of the invention, the composition can include
any one or more
additional ingredients or adjuvants such as. a sweetener such as sucralose or
sodium
saccharin; flavoring; colorant; a preservative. It is also possible to include
a pH adjuster,
as known in the art.
[00169] Embodiments of the invention may include one or more sweeteners
such
sucralose or saccharin, sodium saccharin, sodium cyclamate, sucralose,
steviolglycodes,
aspartame, acesulfame, xylitol, neotame. A possible starting point could be to
use a
concentration of about 0.3% to 0.5% saccharin, optionally combined with up to
0.1%
sucralose. Sodium saccharin is a sweetener, benzoic sulfimide (C7H5NO3 S,
having a
Molecular weight of 183.18 g/mol). Compositions of embodiments of invention
may
include from about 0.1 to about 2.0% concentration of flavoring agents.
Flavoring agents
can include but are not limited to: peppermint oil, spearmint oil, mixtures of
mint oils,
oil of wintergreen, clove oil, lemon oil, orange oil, grapefruit oil, lime
oil, licorice, methyl
salicylate, cinnamon, methyl cinnamate, ethyl cinnamate, butyl cinnamate,
ethyl
butyrate, ethyl acetate, eugenol, eucalyptol, anethole, carvone, menthone,
thymol, cineol,
methyl salicylate, vanilla, vanillin, carvone, licorice, thymol, menthol.
[00170] Sweetening agents suitable for these dentifrice embodiments
include saccharin,
sodium saccharin, sucralose, neotame, acesulfame, thaumatin, glycyrrhizin.
These
substances are hydropolymers. In embodiments of the invention, the composition
can
include any one or more of sweeteners such as saccharin, adjuvants such as: a
sweetener
such as sucralose or sodium saccharin; flavoring; a preservative. It is also
possible to
include a pH adjuster, as known in the art.
Tartar control and chelating agents
[00171] A significant portion of the population suffers from tartar
(also known as
calculus) build-up on their teeth. This is dependent on the calcium content of
their saliva,
and often increases due to misalignment of teeth, which causes calcium
phosphate
deposition on and between teeth. Compositions of embodiments of the invention
can
include a tartar control agent such as pyrophosphate, tripolyphosphate and
hexametaphosphate salts, and zinc chloride, zinc citrate or other zinc salts.
These
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complex phosphates are also useful in preventing stain build up in the tooth
surface and
for supporting claims of tooth whitening.
[00172] Embodiments of the invention may comprise tartar control agents
including
Maleic acid copolymer, beta-D-galactose, beta-D-N-acetyl glycosamine, lactose,
L-
rhamose, beta-D-fucose (US Patent 4,362,713, US patent 5,362,480; US Patent
#4,775,525). Embodiments of the invention may comprise 1-20% Sodium alginate
(average Molecular Weight 222), which helps to remove plaque by chelating
calcium.
Embodiments of the invention may comprise anti-plaque polysaccharide (US
Patent
#4,855,128) in a concentration of from 0.0025% to 1%. Such polysaccharides may
be
selected from the group consisting of lactobionic acid, xanthan gum, guar gum,
gum
tragacanth, guar gum, polygalacturonic acid, as long as they do not degrade
the frictional
properties of the composition as described elsewhere herein.
[00173] Embodiments of the invention may comprise an orally safe
chelating agent. A
known chelating agent for general (non-dental) applications is EDTA
(ethylenediaminetetraacetic acid). However, EDTA might not be a desirable
ingredient
for dental applications. As an alternative, compositions of embodiments of the
invention
may comprise sodium gluconate. Sodium gluconate is a known and safe chelating
agent
that may sequester calcium during brushing. Other orally-safe chelating agents
could also
be used. Also, sodium alginate (average Molecular Weight 222), which helps to
remove
plaque by chelating calcium, could be used.
[00174] Tooth sensitivity often develops in the teeth of people in
their thirties or forties.
It is caused by receding gums which exposes dentin which is normally below the
gum
line. Dentin contains tiny tubules, which allows changes in pressure to the
nerves within
the pulp. Nerve sensitivity can be controlled using potassium salts such as
potassium
nitrate Newer technology provides for ingredients which are deposited on the
exposed
dentin thereby blocking tubules Because this toothpaste described herein
contains only
small quantities of hard abrasives which might remove protective mineral
layers on
exposed dentin, or maybe no such abrasives at all, the use of a toothpaste
formulation of
embodiments of the invention might be especially desirable for people who
suffer from
tooth sensitivity. In embodiments of the invention, the composition may
comprise a)
potassium nitrate; b) arginine; c) LAE; d) other anti-sensitivity compounds.
In
embodiments of the invention, the use of cationic compounds in combination
with SLS
may be avoided, because SLS is anionic and will neutralize the cationic
compounds.
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Arginine 8%, which can be included for sensitive teeth, is an agent to reduce
sensitivity
of teeth. It modifies the pH of the saliva so as to cause precipitation of
calcium into
tubules. This contributes to clogging the tubules that create the sensitivity.
Also, for
people who have sensitive teeth we can take a typical toothpaste and reduce
silica and it
lowers sensitivity for people who have sensitive dentin or teeth. Also,
Sensodyne
toothpaste contains a local anesthetic.
Essential oils
[00175]
Embodiments of the invention can comprise essential oils. An essential
oil is a
substance extracted from a plant, so any natural oil is an essential oil.
Essential oils do
not necessarily act as anti-microbials. However, the term "antimicrobial
essential oils" is
sometimes used in reference to the four natural oils used as antimicrobials in
Listerine,
which have antimicrobial properties. They are (along with the concentration
used in
Listerine mouthwash) 0.042% menthol, 006% methyl salicyl ate, 0.064% thymol,
and
0.092% eucalyptol. The percentages shown are the amounts used as the
antimicrobial
system in Listerine mouthwash. Still other ingredients that are essential oils
or have
antimicrobial properties include the following: Propolis; Aloe vera; Coconut
oil; Cloves
powder; Bloodroot; Limonene.
[00176]
Essential oils may be included in embodiments of the invention that are
toothpastes, mouth washes, chewing gums, or in general any other dosage form
Antimicrobials or antibiotics
[00177]
Embodiments of the invention can comprise any of various antimicrobials
or
antibiotics. Examples of such substances include:
a) cationic surfactants such
benzalkonium chloride, benzethonium chloride, methyl benzethonium chloride,
cetyl
pyridinium chloride and tretradecylpyridinium chloride; b) quaternary amines;
c) CHG
(chlorhexidine gluconate) or CHX (chlorhexidine digluconate) or chlorhexidine
acetate;
d) cetylpyridinium chloride, benzethonium chloride and benzalkonium chloride;
e)
PtIMB (polyhexamethylene biguanide); f) essential oils; g) LAE and
derivatives; h)
others. Stannous fluoride has antimicrobial properties. The ingredient
triclosan, although
not allowed in the US, has antimicrobial properties. For example, compositions
of
embodiments of the invention can be made specifically to treat thrush, yeast
infections
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and fungal infections. Such embodiments may be made as specialty products so
as to be
dispensed for particular patients.
Preservative
[00178] Embodiments of the invention may include a preservative. It is
possible that a
preservative will not be needed in this formulation. Especially, if the water
activity of
the toothpaste is reduced to 60% or less, bacterial and fungal growth would
likely be
prevented even without the use of a preservative. There are many preservatives
that
could be used if desired, usually coupled with a buffer to adjust the pH to a
mildly acidic
range of about 5 to 5.5.
Humectant-rich compositions, and categories of compositions according to
amount of humectant
[00179] In some embodiments of the invention, the composition may
comprise as large a
concentration as possible of humectant and as small a concentration as
possible of water.
Such composition may be referred to as a nearly non-aqueous formulation. In
addition to
providing a suitable water activity of the composition, such situation may
also have a
benefit in regard to enhancing the entanglement of the Minute Fibrils. Such
situation also
may have a benefit in regard to the Superabsorbent Polymer, if such is
included in the
composition.
[00180] In regard to the amount of water that is contained in the
composition, there may
be some amount of water that is present unavoidably for reasons related to
manufacturing. One reason for this is the fact that MFC is supplied
commercially not in
a dry condition, but rather as water-based paste. For example, MFC supplied by
Borregaard is supplied in the form of a paste that contains 10% MFC, 90%
water. MFC
that is supplied by Weidmann is supplied in the form of a paste that is 30%
MFC, 70%
water. Reasons for this are discussed in US patent 4,374,702 to Turbak and US
patent
4,481,077 to Herrick. Turbak describes that a basic process for preparing MFC
can
involve pumping a suspension of cellulose fibers through a high pressure jet
creating
shearing action and impinging or impacting. It is further described in Herrick
that it is
beneficial if the fibrillated material is never fully dried, because
fibrillated material that
is dried and then resuspended in water does not perform exactly as it did
before the drying
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and resuspension. Further, it is disclosed in Herrick that if a liquid present
around the
fibrils includes a compound capable of substantially inhibiting hydrogen
bonding of the
fibrils. Water is not such a compound, but that category includes many organic
liquids.
In particular, included in that category are liquids that are of interest as
humectants.
Herrick indicates that it is further possible to evaporate water from liquid-
MFC
suspension after the other liquid has been introduced, such as by vacuum
evaporation.
[00181] A further source of water is the possible use of sorbitol as a
humectant or as one
of a combination of humectants. Sorbitol is a solid at room temperature but is
highly
soluble in water. It is usually supplied in the form of an aqueous solution
containing 70%
sorbitol and 30% water. However, various other humectants can be used instead
of
sorbitol, and so sorbitol humectant does not have to be a source of water in
the
composition. In addition to sorbitol, it is possible that there could be some
other
ingredients that might be introduced to the composition as aqueous solutions,
such as
surfactants, flavors, etc
[00182] In regard to numerical values of concentrations, it is possible
that a composition
of an embodiment of the invention could contain an MFC concentration of
approximately
2%, referring to the fibrillated MFC material itself If the MFC is added to
the
composition in the form of a paste that contains one-tenth MFC and nine-tenths
water,
then the composition would contain, in addition to the 2% MFC, a water
concentration
of 18%. This is how concentrations of ingredients in the compositions are
reported
herein. If the composition further contains 35% glycerin, as is the case for
some
embodiments, then the composition would be a majority-non-aqueous composition.
[00183] In addition to the majority-non-aqueous composition just
described, other
alternative compositions of embodiments of the invention could have a carrier
liquid that
is either entirely water or mostly water. Such embodiments have been described
in patent
application U.S. Serial No 17/062,424 and PCT/US2020/054149. Although they may
have high water activity, they may be made resistant to microbial growth by
including
preservatives.
[00184] In still other embodiments, compositions could contain These
are based mixtures
of water and humectants; sometimes there is a larger concentration of
humectants than
of water. This class of formulation can be made to exhibit low water activity
between 0.7
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and 0.75 and in this context embodiments of the invention are equivalent to
commercial
and prior art toothpaste formulations.
[00185] It is found experimentally that even with the presence of
humectants (e.g.,
propylene glycol, glycerol or sorbitol or their mixtures, at a total humectant
concentration
as large as 45%) in the toothpastes of an embodiment of the invention, the
compositions
were remarkably effective in removing highly adhering biofilms.
Referring now to Figures lA and 1B, there are shown micrographs
Microfibrillated Cellulose in two different carrier liquids. Figure lA shows
MFC in
water as a carrier liquid, and it can be seen of that there is an intense
aggregation of
fibrils (i.e., flocs) with voids in between those aggregates. This would be
typical of the
low-humectant compositions disclosed in US Serial Number 17/062,424 and PCT
patent application PCT/US2020/054149. In Figure 1A, 35% of the area (with a
likely
standard deviation of about 5%) is occupied by large (>> 10 microns in
diameter)
microstructural voids that contain little or no MFC The other 65% of the area
is
occupied by MFC. In other words, about a third of the material microstructure
is
occupied by MFC-depleted large voids. These numbers could be influenced
somewhat
by the overall concentration of MFC in the composition. In Figure 1B, the
higher
concentration of humectant (a concentration of 30-35-40% humectant) causes the
fibers
MFC to have a different microstructure because it makes the MFC more dispersed
more highly dispersed and more uniformly dispersed and it is apparent that
voids do not
occur as they did in Figure 1A. In Figure 1B, with high concentration of
humectant
(35% glycerol), the fibrils extend all over and voids are essentially absent.
There is no
intense aggregation as was seen in Figure lA for the mostly-water case. A floc
is a
fibrillated entity or a plurality of fibrillated entities entangled with each
other. A floc
can be measured by laser diffraction at a very dilute condition. In many
situations, an
individual floc may not be particularly visible, but they can be seen once the
composition is sufficiently diluted. Figure lA shows a microstructure
comprising
highly aggregated MFC flocs (A) and voids (Light shaded area B). Figure 1B
shows a
uniformly dispersed MFC within the microstructure without visible voids.
Some compositions of embodiments of the invention comprise both MFC and
high humectant concentration, thereby producing a unique and beneficial
microstructure. This is shown in Figure 1C. The embodiment composition is made
with surface crosslinked SAP. SAP particles appear as light shaded irregularly
shaped
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objects (circled by yellow circles). This is an example of a "thirsty"
composition,
having no voids, ready to absorb water.
It is believed that in embodiments of the invention, the abrasive silica
particles
become wrapped-up by the MFC fibers/fibrils thereby strenghtneing the
mechanical
properties of the network and possibily contributing an improvement towards
stain
removal as compared to the same concentration and type of abrasive silica
dispersed in
commercial toothpastes that lack the network. In Figure 1D we show the
evidence of
abrasive silica trapped within MFC, with the carrier liquid being water. In
Figure 9 we
report the resulting increase in viscosity (viscous modulus) and elasticity
(storage
modulus) when using a 19% concentration of abrasive silica (Zeodent 113) as
compared to a 5% concentration of abrasive silica (Zeodent 113) in a solution
of water
containing 1.5% MFC. Figure 1D shows abrasive silica particles incorporated
within
the fibrillated entity (A), and void (B) does not contain loose abrasive
particles.
Figure 9 shows linear viscoelastic response of a composition made with 1.5%
MFC in
water with 5% and 19% abrasive silica (Zeodent 113).
In an embodiment we unexpectedly discovered that the abrasive hydrated silica
particles become wrapped-up and incorporated by the fibers/fibrils of the
microfibrillated network structure. Figure 1D is a microscopic image that
shows
abrasive silica trapped within the fibrillated structure with no loose
particles observed
in the voids between the fibers and fibrils, even when the compostion is
diluted down to
50% of tis original concentration with water. This new microstructure is
different from
prior art commercial toothpaste (Figure 1E), in which abrasive silica is
loosely
dispersed in the polymeric matrix. In Figures 1D, 1E, abrasive particles are
the darkest
particles. Light gray regions in Figure 1D indicate liquid regions which are
void. Also
in Figure 1D, it is possible to see fibrous with abrasive particles entrapped
incorporated
in fibrillated structure. The dark abrasive particles do not tend to be in the
void (liquid)
regions. In Figure 1E (right), commercial toothpaste has an appearance
resembling
gravel. Figure 1E shows commercial toothpaste with abrasive particles loosely
di stri buted everywhere within the material.
Embodiment compositions haying SAPs ¨ thirsty compositions
[00186] In embodiment compositions that include particles of a
SuperAbsorbent as
described elsewhere herein, it is believed that it may be desirable to provide
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SuperAbsorbent Polymer in combination with a carrier fluid that may contain
some water
but has a high concentration of liquid humectant. It can be expected that in
such a
situation, in the toothpaste as delivered at the start of toothbrushing, the
particles of SAP
have not absorbed the equilibrium amount of water that they are capable of
absorbing.
Thus, they remain capable of absorbing additional water during the process of
tooth
brushing. In particular, this means that the SAP particles can absorb some
saliva water
produced during tooth brushing. It is believed that when saliva or water is
absorbed by
the SAP particles in this manner, that saliva or water is unavailable to cause
the type of
dilution that could cause the network of embodiments of the invention to
become less
effective in removing biofilm. In such a situation, the non-SAP components of
the
toothpaste can be expected to behave as though they were less diluted than one
might
expect from overall parameters. Therefore, behavior such as dilution-induced
weakening
of the network may be less severe than one would otherwise expect, and
performance of
the toothpaste for removal of dental biofilm may be improved. Persons skilled
in the art
may vary the type of SAP and humectant and their ratio to arrive at optimal
performance
with respect to removing plaque, stain or other residues. This embodiment is
not meant
to be limited to particular compositions. For example, it is applicable even
to
compositions that might not include minute fibrils or fibrillated materials.
The goal of
the embodiment is providing a new strategy to minimize the effect of saliva-
induced
dilution in toothpaste composition, broadly.
[00187] Embodiments of the composition can be made by considering the
SAP CRC
values and the water holding capacity (WHC) of the minute fibrils. The amount
of water
used in the composition can be less than the sum of CRC and WHC, meaning that
the
water used in the composition will be less that the amount required to obtain
equilibrium
swelling or hydration. These requirements can be satisfied by using humectant-
water
carrier liquid to make the composition. According to embodiments, this
"thirsty"
composition would have the propensity to remove water from mouth during the
duration
of brushing, and this would prolong the time during which the network
maintains its
favorable rheology and structure. The rate of removing water during brushing
can be
adjusted by selecting the type of SAP, its CRC value, its concentration, its
rate of water
absorption and the type and level humectant in the carrier fluid. It is
believed that some
of water removal may be arising from the humectant and minute fibril
components of the
composition. Persons skilled in the art may manipulate compositions to make
such thirsty
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compositions according to the teaching of embodiments. The goal of making such
composition is the reduction of the effect of saliva-induced dilution during
brushing and
maintaining the integrity of toothpaste structure so that optimal biofilm
removal can be
obtained. The invention is not intended to be limited to SAP, humectant,
minute fibrils
or other elements of composition.
[00188] In embodiments of the invention, the Minute Fibrils themselves
also have a
substantial water holding capability. In embodiments of the invention, it is
possible to
achieve water retention in the Minute Fibrils.
[00189] In some embodiments of the invention, the carrier liquid may
comprise water and
a concentration of one or more humectants. The total concentration of
humectant(s) in
the composition may be 20%, 30%, 40% or even 50% of the composition. The total
concentration of humectant(s) in the composition may be larger than the
concentration
of water in the composition. At the same time, in embodiments of the
invention, the
composition also comprises particles of SuperAbsorbent Polymer. In addition to
whatever effect the particles of SAP might directly contribute to cleaning,
the ability of
the SAP to absorb water may discourage syneresis and also may help to
counteract the
effect of dilution of the composition by saliva or water during use. Such
dilution, if it
occurs, might lessen the ability of the network to effectively cause cleaning
action,
because in a dilute situation the fibers/fibrils might become more distant
from and
separated from each other. Therefore, if water that might cause dilution of
the network
is captured by the particles of SAP, then that water would no longer be
available to dilute
or harm the network because the water would be sequestered inside the
particles of SAP
and would be unavailable to contribute to the loosening of the network. As a
result, the
composition would effectively contain less free water than might be expected
based on
overall proportions of the composition (including possible water/saliva added
during
brushing). In regard to the humectant that is present in the composition,
presumably, the
humectant would not be absorbed by the SAP, but rather would remain as liquid
among
the fibers/fibrils and other non-liquid components of the composition.
[00190] It is possible to quantify this criterion regarding the ability
of the SAP to sequester
water. A parameter that is descriptive of SuperAbsorbent Polymer is the
Centrifuge
Retention Capacity, which is the amount of pure water that can be held by the
SAP per
unit mas of the dry SAP. While some SAP can have a CRC value of several
hundred g/g,
it is believed that the form of surface cross-linked SAP or highly bulk cross-
linked SAP
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that is desirable for embodiments of the invention can have a CRC value of 10-
30 g/g.
So, as an example calculation, if a composition contains a 50% concentration
of water
and 2% concentration of SAP, and if SAP has a CRC value of 25, then that
concentration
of SAP could absorb all of the water that is present in the composition. If a
concentration
of SAP is still larger than the amount just described, then even if the SAP
were to absorb
all of the water that is present in the composition, the SAP still would have
additional
capacity to absorb more water such as water/saliva introduced during brushing.
This
criterion can be expressed as:
CRC * [concentration of SAP] > [concentration of water]
[00191] Accordingly, in embodiments of the invention, the concentration
of the SAP,
multiplied by the CRC value of the SAP, may be greater than the concentration
of water
in the composition. As a further example, in embodiments of the invention, the
concentration of the SAP, multiplied by the CRC value of the SAP, may be two,
or more,
times the concentration of water in the composition.
[00192] A further consideration is that the MFC fibers themselves have
some ability to
absorb water. In regard to this, the ability of fibrillated material itself to
absorb water
may act in somewhat the same way as the ability of SAP particles to absorb
water. The
parameter describing this is the Water Holding Capacity, WHC, also expressed
in grams
of water per gram of the material in question, namely MFC. Adding additional
detail to
the previous equation, this effect can be described as:
CRC *[ concentration of SAP] + WHC *[concentration of MFC] > [concentration of
water]
[00193] As a further example, in embodiments of the invention, the left
side of the
equation can be not just slightly greater than the right side, but could be a
factor of two
or more times the right side. It is believed, although it is not wished to be
limited to this
explanation, that during toothbrushing, when this water sequestration occurs,
the network
lasts longer and is more effective at removing plaque biofilm and stain than
would
otherwise be the case It is believed that the SAP does not absorb humectant,
and it is
believed that the MFC fibrils do not absorb humectant either. It is believed
that they only
absorb water.
[00194] In an embodiment of the invention, the liquid content of the
composition may be
approximately 50% water and 50% humectant. In an embodiment of the invention,
due
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to the remaining water-absorbing capacity of the SAP (and possibly the
fibrillated
material), the composition may be able to absorb an additional volume of pure
water that
is equal to the volume of the composition itself, or may be equal to half such
volume.
Sequence of manufacturing steps, especially for humectant-rich compositions
[00195] An embodiment of the invention can also include a method of
manufacturing
some of the described compositions such as the "thirsty SAP" embodiment.
Compositions of an embodiment of the invention may be made according to the
following steps:
[00196] (A.) Solid ingredients of the composition such as MCC or
similar solid particles
and particles of SAP and possibly some of the abrasive silica and titanium
dioxide are
first suspended in pure humectant or in a humectant-water mixture, and then
are
homogenized to disaggregate them and to create a homogeneous uniform
dispersion.
[00197] (B) Then, a portion or all of the fibrillated materials of the
composition is added
to the just-created dispersion in a sufficient amount/concentration so that
the fibrillated
material can form a protective adsorbed layer on the surface of the SAP
particles. This
adsorbed layer will stabilize them and prevent them from collapsing/coalescing
with each
other inside the composition.
[00198] (C) After mixing the solid particles and SAP in with the
humectant or in the
humectant-water mixture, the resulting composition is then homogenized to form
a
network where the solid particles and the coated-SAP particles become fully
incorporated
within the fibrillated network. The resulting composition becomes thick in
consistency,
has viscoelastic properties and possesses a yield stress as described
elsewhere herein.
[00199] (D) After the fibrillated materials, solid particles and SAP
are incorporated
uniformly in humectant or the humectant-water mixture as described above,
other solid
ingredients including: additional fibrillated materials, remaining abrasive
silica,
remaining titanium dioxide and other ingredients as described elsewhere herein
can be
added and mixed with the above formed material under sufficient shear possibly
with
other type of mixing equipment and for a sufficient period of time to ensure
the
production of a uniform composition. Afterwards, the surfactant, flavors,
sweeteners and
preservatives are added to the above mixture and are then mixed to prepare the
final
toothpaste composition.
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Dilution of toothpaste
[00200] It is desirable that viscoelastic properties should remain in
the effective range for
removing biofilm (having a yield stress more than 10 Pa and having an elastic
modulus
or storage modulus greater than 1000 Pa) preferably for the duration of
brushing or at
least for more than 30 seconds and more preferably for more than 1 minute and
most
favorably for 2 minutes. It is desirable that these properties be maintained
even with
dilution to 50% of the original concentration of the composition. It is even
more desirable
if these properties can be maintained upon dilution to 33% or 25% of original
concentration of the composition. Maintaining the viscoelastic properties of
embodiment
compositions at effective levels to remove biofilm plaque during brushing
needs to be
considered depending on the velocity and shear rates generated by the type of
brush used.
For example, conditions for effective biofilm removal may vary to some extent
on
whether manual, mechanical or sonic brushed are used to perform toothbrushing,
as
detailed in patent application U.S. Serial No. 17/062,424 and PCT patent
application
PCT/US2020/054149 both filed October 2, 2020.
Applicators and Dosage Forms
[00201] Although dentifrices such as toothpaste are prominent
embodiments of the
invention, dentifrices are not the only vehicle which can be used to
physically remove
plaque-biofilm from teeth using these embodiments. For example, effective
plaque
removal can be obtained using, for example, an oral device, such as a Water
Flosser
(Waterpike, Fort Collins, Colorado), which forcefully delivers a stream of
liquid
composition onto and between teeth. Mechanical action can also be delivered by
chewing a gum with compositional embodiments to dislodge and remove biofilm.
Mechanical forces can also be supplied simply by thoroughly rinsing the mouth
with a
suitable mouthwash. Hence, while many of the embodiments discussed apply to
compositions like dentifrices, it is envisioned that inventive compositions of
different
dosage forms, such as a mouthwash, a pre-rinse or a solid composition, such as
a chewing
gum, can be employed as embodiments as herein described.
[00202] One useful application of these embodiments is a dentifrice in
the form of a
toothpaste, tooth-gel, dental-cream, tooth-liquid or tooth powder which
maximize the
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ability of the toothbrush or other suitable applicator to physically remove
plaque-biofilm
from teeth during brushing. Included in dentifrice embodiments are a
prophylaxis paste,
a prophylaxis gel, a prophylaxis powder for in-office stain removal and
polishing of teeth
by a dental professional. Another dentifrice embodiment is a professionally
prescribed
or applied high fluoride oral gel for patients at high risk of dental caries
or who exhibit
signs of early carious lesions such as white spots.
[00203] An oral composition of these embodiments can be supplied in
almost any form
such as a liquid, a spray, a semisolid, a paste, a gel, or a cream, which has
a pre-formed
3D, entangled, viscoelastic structure in a liquid medium, or it can be in the
form of a dry
solid, a dry powder, a gum or an anhydrous paste or gel, which forms such a
3D,
entangled, viscoelastic structures when mixed with water or when mixed with
saliva
during use. By dry, we mean that the dry solid or dry powders are not wet with
significant
concentrations of unabsorbed liquid components, such as liquid water, liquid
humectant,
or liquid surfactants that would make the compositions seem moist, i e , the
compositions
are dry to the touch.
[00204] It has surprisingly been found that certain combinations of
natural or synthetic
polymers can be formulated into effective plaque-biofilm dislodging and
removing
compositions that are much more effective in physically displacing plaque-
biofilm from
on and between teeth than currently marketed conventional oral care
compositions. For
example, twice daily brushing with a dentifrice incorporating these
embodiments
physically removes significantly more plaque-biofilm from the dentition, than
a
conventional toothpaste. Thoroughly rinsing the mouth with a mouthwash
embodiment,
is more effective in displacing plaque biofilm from the teeth than rinsing
with a
conventional mouthwash. A special pre-brushing mouth rinse can deliver plaque-
biofilm
dislodging embodiments prior to regular brushing. Subsequent brushing will
supply the
forces needed to promote plaque-biofilm removal to better remove plaque
biofilm. An
advantage of such a pre-rinse is that users can get the benefits of the plaque
removing
components, while using a toothpaste composition of their own choice. Chewing
gum
embodiments can provide a way for health-conscious individuals to dislodge
plaque and
rid biofilm from their teeth after meals or at other times between regular
oral-hygiene
procedures when brushing is not possible. Plaque-biofilm removing embodiments
not
only include personal care compositions, but also compositions used or
prescribed by
dental professionals, such as prophylaxis pastes, fluoride treatment
compositions and
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tooth preparations used to more effectively clean tooth surfaces prior to
fillings,
extractions or root canal surgery. Such compositions can be formulated with or
without
abrasives, which might otherwise damage enamel or exposed dentin. Indeed, it
is also
envisioned that a careful subgingival cleaning of the teeth with a periodontal
treatment
embodiment by a dental professional can effectively remove pathogens from
periodontal
pockets and provide the basis for a highly effective non-surgical treatment
for
periodontitis.
Modes of Action
[00205] While not wishing to be bound by any specific modes of action,
we propose a
combination of several mechanisms to account for the highly effective
displacement of
plaque-biofilm from the dentition by the ingredients in the dentifrice. We
believe that the
polymeric components contribute to the composition's ability to remove plaque
biofilm
in several ways. During brushing, the fibrils from the micro-fibrillated
polymeric
component play a direct role in penetrating the narrow spaces, such as between
closely
spaced adjacent teeth, within fissures in teeth, and also along the upper and
lower
crevices formed at the gingival margins, i.e., where the upper and lower teeth
emerge
from the gums. The fibrils and micro-fibrils reach into, entrap, and extricate
plaque, from
these aforementioned areas, which would normally be inaccessible. Also, when
added to
an aqueous medium, both the micro-fibrillated component and super absorbent
polymers
absorb water and swell. The micro-fibrillated components, together with the
organic
polymeric thickener, create a viscoelastic fluid enveloping the water-
insoluble, entangled
3D fibrillated network. During toothbrushing, the viscoelastic dentifrice
fluid transfers
the applied brushing forces to the biofilm and displaces it from tooth
surface. Due to the
characteristics of the viscoelastic dentifrice, the formation of a depletion
layer, which
would otherwise inhibit biofilm removal is minimized. Contributions to biofilm
removal
efficacy are also made by the microcrystalline cellulose, abrasive particles
(e.g., silica),
the silicified microcrystalline cellulose, the nanocrystalline cellulose
and/or the
powdered cellulose ingredients, which use mild frictional forces to ensure
superior
plaque removal from tooth surfaces. By "mild frictional forces-, we mean weak
lateral
forces applied by the dentifrice ingredients to wipe biofilm from the tooth
surface, even
is the areas and zones between the bristles on the brush. It should also be
further noted
that the surfactant "foaming agent" may have a role in reducing the surface
tension or
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interfacial forces between the biofilm and the tooth surface and thereby help
in loosening
its surface adherence.
[00206] Without being limited by possible specific modes of action, it
is proposed that
alone or in combination with other solids, these polysaccharide fibers and
fibrils form 3-
D entangled network structures when added to aqueous carriers. The resulting
compositions are viscoelastic and have a yield stress more than 10 Pa and have
an elastic
modulus or storage modulus greater than 1000 Pa and preferably higher. Hence,
one of
the functions of these materials is to modify the tribology and better direct
the brushing
forces through the dentifrice to achieve appropriate values of these
parameters. As a
result, it has been found that when compositions of embodiments of the
invention are
driven by the toothbrush or applicator over the surface of the teeth, the
solid particles in
conjunction with the network physically remove biofilm, even highly
challenging
biofilm, from the surfaces being cleaned. This contrasts with most commercial
toothpastes, which are generally found to be ineffective in physically
increasing rem oval
of plaque biofilm. Another aspect of modifying the dentifrice tribology is to
access tight
spaces on and between the teeth where a normal toothbrush or conventional
toothpaste
cannot reach. We also believe that one of the advantages of using natural
particulate
polysaccharides is that they provide a surface to which plaque biofilm can
attach and as
a result help its removal when the dentifrice is expectorated after brushing.
[00207] These characteristics of the compositions, whether their
geometry is fibrous or
particulate or something else, significantly improve the physical displacement
of oral
biofilm, food residues and other undesirable materials from teeth and result
in reduced
gingivitis, less tooth decay and less tooth loss and hence better oral health.
[00208] It is additionally proposed that, during brushing, the lectins
on the polysaccharide
fibrils make contact and bind with adhesins on the biofilm bacteria, thereby
releasing
them from lectins in pellicle and on mineral surfaces to which they initially
adhere.
[00209] Another worthwhile group of oral embodiments are oral care
liquid or solid, oral
care compositions, which include, for example, chewing gums, tablets,
lozenges,
mouthwashes, mouth rinses, oral pre-rinses and fluid compositions used with an
oral care
device, such as a Water Flosser (Waterpik , Fort Collins, Colorado).
[00210] While not wishing to be bound by any specific modes of action,
we propose that
liquid compositions, such as mouthwashes, remove plaque by similar mechanisms
to
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those we proposed for dentifrices. It is believed that, during thorough
rinsing, the fibrils
and micro-fibrils from the micro-fibrillated polymeric component penetrate the
narrow
spaces, such as on and between teeth, along the gum line, in fissures etc. and
extricate
plaque-biofilm, which would normally be inaccessible. The micro-fibrillated
component,
in combination with other water absorbing and swelling polymers SAP or NSAP
and the
organic polymeric thickeners, form a viscoelastic fluid around the water-
insoluble,
entangled 3D fibril network. Thorough rinsing with a mouthwash embodiment, or
other
forceful actions of delivery of the viscoelastic fluid to the teeth, forces
the liquid
composition into areas of the teeth that otherwise are difficult to access.
[00211] Among other potential oral care compositions, are a pre-rinse
embodiment which
helps to dislodge and remove plaque-biofilm prior to and during brushing. A
pre-rinse,
which adds to the effectiveness of a dentifrice, can be attained by providing
shear-
thinning (pseudoplastic) viscosity characteristics. While the pre-rinse is in
motion during
rinsing, the viscosity of the liquid composition is greatly reduced, allowing
the liquid to
reach virtually all areas of the dentition. After the rinsing action ceases,
the composition
viscosity will increase, due to the pseudoplastic characteristics, leaving a
gel-like film of
the rinse on the plaque particularly in places where plaque biofilm builds up,
such as
between teeth. Subsequent brushing with or without toothpaste will allow
residual
polymeric plaque dislodging and removing ingredients in the residual film from
the
mouth pre-rinse to displace and remove more biofilm. Of course, as discussed
previously, contributions to biofilm removal are also made by the
microcrystalline
cellulose, the silicified microcrystalline cellulose, the nanocrystalline
cellulose and/or
powdered cellulose ingredients in the rinse, which provide mild frictional
forces to
improve biofilm removal.
Compositions as described by numerical ranges
Following are example compositions:
For Dentifrices (such as toothpaste)
[00212] Dentifrice compositions, of embodiments of the invention,
may comprise:
(A) the aforementioned ingredients, which physically dislodge and remove
plaque-biofilm comprising:
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(1) From about 0.1% to about 10% of an oral-plaque-biofilm removing,
water-insoluble, hydratable, natural or synthetic, fibrillated or micro-
fibrillated, polymer, which swells and thickens in an aqueous medium,
together with one or more of the following additional plaque removing
components:
(2) From about 0.1% to about 5% of a water-insoluble, micro-crystalline
cellulose (MCC) or a water-insoluble, silicified, microcrystalline
cellulose (SMCC) (the concentration could be larger in the case of a
chewing gum or a dry dosage form);
(3) from about 0.1% to about 5%, of a synthetic, superabsorbent
polymer (SAP), which may be surface cross-linked but does not have to
be, or a natural, super absorbent polysaccharide (NSAP), and which
swells and thickens in an aqueous medium;
(4) from about 0.1% to about 10% of a natural or synthetic, water-
insoluble, nanocrystalline cellulose polymer (CNC), derived by
acidification or oxidation of a natural or synthetic cellulose;
(5) from about 0.1% to about 4% of one or more water-soluble, organic,
polymeric thickeners (PT), selected from an alkali metal or ammonium
salt of a poly acrylic acid, xanthan gum, carrageenan gum, an alginate
salt, sodium carboxymethyl cellulose, hydroxym ethyl cellulose,
hydroxyethyl cellulose and hydroxypropyl cellulose;
(6) from about 0.1% to about 15% of a natural or synthetic, water-
insoluble, powdered cellulose (PC).
(B) Functional dentifrice ingredients, which deliver the additional cleaning,
oral
care, health care and aesthetic benefits expected of a dentifrice composition
comprising:
(i) From about 5% to about 65% of an abrasive;
(ii) From about 0.1% to about 2.0% of a flavoring agent;
(iii) Optionally, from about 0.05 to about 1% of a sweetener, selected
from saccharin; sodium saccharin, sucralose, aspartame, Stevia,
potassium acesulfame, neotame, thaumatin, sodium cyclamate;
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(iv) Optionally, from about 0.2% to about 2.0%, preferably from about
0.4% to 2.0% of a surfactant;
(v) Optionally, from about 0.1% to about 2.0% of a preservative;
(vi) Optionally, from about 0.2% to about 2.0%, preferably from about
0.5% to about 1.5%, of a buffer to provide a pH between about 3.5 and
9.5, the exact pH range chosen will depend on the fluoride chosen, if
there is one, and the needs of other ingredients selected;
(vii) Optionally, sufficient colorant, such as an FD&C dye, or an
opacifier, such as titanium dioxide, to impart a desirable color or
whiteness to the dentifrice
(viii) Optionally, from about 0.05% to about 1.0% of an emulsifier
(ix) Optionally, a fluoride source, selected from sodium fluoride,
sodium mono-fluorophosphatc, stannous fluoride and an amine fluoride,
in an amount to provide from about 0.025% to about 1% of fluoride-
ions;
(C) And additionally, may also comprise one or more of the following optional
performance broadening agents, selected from:
(x) A tartar control agent, present in a concentration of from about 0.1%
to about 5%, selected from the following: a complex phosphate salt, zinc
citrate, zinc lactate, zinc chloride, an alkali metal polyacrylate, and an
ammonium polyacrylate salt, alkali metal gluconate and an ammonium
gluconate salt;
(xi) A tooth desensitizing agent selected from about 0.1% to about 7%
of potassium nitrate salt, from about 0.1% of a strontium salt and a
stannous salt;
(xii) A non-abrasive stain removing agent selected from sodium citrate,
and a complex phosphate salt.
(xiii) A non-abrasive tooth whitening agent the ingredient selected from
hydrogen peroxide, carbamide peroxide. sodium percarbonate, and
sodium perborate.
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(xiv) A breath deodorizing component such as Eucalyptol, Zinc
Chloride, Methyl Salicylate, Thymol, Menthol.
(D) the composition is mixed, suspended, dispersed, emulsified or partially
dissolved in about 4% to about 50% of a carrier selected from one or more of
the following:
(xv) water;
(xvi) a humectant selected from glycerin, sorbitol, 1,2 propylene glycol.
1,3 propanediol, polyethylene glycol, sorbitol, polypropylene glycol,
erythritol, and xylitol;
(xvii) (in the case of a tooth powder or a chewing gum) a powdered
flake or solid substance selected from one or more of the following: a
solid, a gum and a powder. Cellulose, micro-cellulose, hydrated silica,
precipitated silica, amorphous silica, precipitated silica, a silica xerogel,
polyethylene glycol with a molecular weight above about 650, sorbitol,
mannitol, maltitol, isomalt, calcium sulfate, gypsum, magnesium sulfate,
hydrated magnesium silicate, talc, sodium bicarbonate, bentonite,
sodium carbonate, calcium carbonate, dicalcium phosphate dihydrate,
anhydrous dicalcium phosphate, calcium pyrophosphate, tricalcium
phosphate, calcium metaphosphate, a gum bases, a wax, stearic acid.
For Liquid dosage Form (such as mouthwash)
[00213] Oral liquid and other compositions of embodiments of the
invention, may
comprise:
(A) ingredients, which physically dislodge and physically detach plaque-
biofilm
including:
(1) from about 0.02% to about 8% of an oral, plaque-biofilm removing,
water-insoluble, hydratable, natural or synthetic, fibrillated or micro-
fibrillated, polymer, which swells and thickens in an aqueous medium,
together with one or more of the following additional plaque removing
components:
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(2) From about 0.1% to about 5% of a water-insoluble micro-crystalline
cellulose (MCC) or a water-insoluble silicified microcrystalline
cellulose (SMCC);
(3) from about 0.1% to about 5%, of a synthetic surface cross-linked
superabsorbent polymer (SAP), or a natural, super absorbent,
polysaccharide (NSAP), and which swells and thickens in an aqueous
medium;
(4) from about 0.1% to about 2% of a natural or synthetic water
insoluble nanocrystalline cellulose polymer (CNC) derived by
acidification or oxidation of a natural or synthetic cellulose;
(5) from about 0.1% to about 4% of one or more water-soluble, organic,
polymeric thickeners (PT), selected from an alkali metal or ammonium
salt of a polyacrylic acid, xanthan gum, guar gum, carrageenan gum,
sodium carboxym ethyl cellulose, hydroxym ethyl cellulose,
hydroxyethyl cellulose and hydroxypropyl cellulose, an alkali metal or
ammonium alginate salt,
(6) from about 0.1% to about 15% of a natural or synthetic water-
insoluble powdered cellulose (PC).
(B) functional ingredients for liquid compositions, which deliver the
additional
cleaning, oral care, health care, breath deodorizing, and aesthetic benefits
expected of a complete oral care, composition comprising:
(iii) Optionally, from 0.01 % to about 0.5% an antimicrobial
agent selected from chlorhexidine, cetylpyridinium chloride,
benzethonium chloride and benzalkonium chloride, and essential
oils, which include menthol, methyl salicylate, thymol, and
eucalyptol;
(iv) From 0% to about 2% of a surfactant;
(i) From about 0.05 to about 2.0% of a flavoring agent;
(ii) From about 0.01% to about 1% of a sweetener;
(v) Optionally, a pH buffer;
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(vi) Optionally, a fluoride source, selected from sodium
fluoride, sodium mono-fluorophosphate, stannous fluoride and
an amine fluoride, in an amount to provide from about 0.025% to
about 0.5% of fluoride ions;
(vi) Optionally, an emulsifier;
(viii) Optionally a preservative;
(ix) Optionally a colorant;
(C) And additionally, may comprise one or more of the following optional
performance broadening agents selected from:
(x) From about 0.1% to about 2% of a tartar control agent
selected from the following: a complex phosphate salt, zinc citrate, zinc
lactate,
zinc chloride, an alkali metal polyacrylate, an ammonium polyacrylate salt, an
alkali metal gluconatc, an ammonium gluconatc salt;
(xi) Potassium nitrate, a strontium salt, a stannous salt;
(xii) A whitening agent selected from hydrogen peroxide,
sodium perborate;
(xiii) Breath deodorizing components selected from 0.05 to 0.7%
cetyl pyridinium chloride, and the essential oils, such as
eucalyptol, methyl salicylate, thymol, and menthol;
And the above ingredients may be mixed, dispersed, suspended or partially
dissolved in:
(D) a carrier selected from:
(i) Water;
(ii) ethanol;
(iii) a powder, a flake or solid substance selected from one or
more of the following: a solid, a gum and a powder, Cellulose,
micro-cellulose, hydrated silica, precipitated silica, amorphous
silica, precipitated silica, a silica xerogel, polyethylene glycol
with a molecular weight above about 650, sorbitol, mannitol,
m al titol, isomalt, calcium sulfate, gypsum, magnesium sulfate,
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hydrated magnesium silicate, talc, sodium bicarbonate, bentonite,
sodium carbonate, calcium carbonate, dicalcium phosphate
dihydrate, anhydrous dicalcium phosphate, calcium
pyrophosphate, tricalcium phosphate, calcium metaphosphate, a
gum bases, a wax, stearic acid;
(iv) and a humectant selected from glycerin, sorbitol, 1,2
propylene glycol, 1,3 propanediol, polyethylene glycol, sorbitol,
polypropylene glycol, erythritol, and xylitol.
[00214] An oral care composition of embodiments of the invention may
comprises an
effective amount of a fibrillated or micro-fibrillated, natural or synthetic,
water-
insoluble, hydratable, polymer (MFC), which swells and thickens in an aqueous
medium
to form a viscoelastic fluid and which physically removes plaque biofilm from
oral
surfaces.
[00215] Another oral composition of embodiments of the invention may
comprise (A)
0.05% to 8% of an oral plaque-biofilm-dislodging and removing, natural or
synthetic,
water-insoluble, hydratable, polymer (MFC), which swells and thickens in an
aqueous
medium to form a viscoelastic fluid which physically dislodges and removes
plaque
biofilm from oral surfaces, together with (B) one or more of the following
biofilm
removing components:
(i) From about 0.1% to about 5% of a particulate, water-insoluble, micro-
crystalline cellulose (MCC) or a particulate, water-insoluble silicified micro-
crystalline cellulose (SMCC);
(ii) From about 0.1% to about 5% of a particulate, synthetic, cross-linked,
Super Absorbent Polymer (SAP), which swells and thickens in an aqueous
medium;
(iii) From about 0.1% to about 5% of a particulate, natural, non-cross-
linked
Superabsorbent Polymer (NSAP), which swells and thickens in an aqueous
medium;
(iv) From about 0.1% to about 2% of a water-insoluble, particulate, nano-
crystalline cellulose polymer (CNC), derived, for example, by acid hydrolysis
of
natural or synthetic cellulose;
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(v) From about 0.1% to about 4% of a water-soluble, organic, polymeric,
thickener (PT), selected from one or more of the following: an alkali metal or
ammonium salt of a polyacrylic acid, an alkali metal or ammonium alginate
salt,
xanthan gum, guar gum, carrageenan gum, sodium carboxymethyl cellulose
(CMC), methyl cellulose (MC), hydroxymethyl cellulose (HMC), hydroxyethyl
cellulose (HEC), hydroxypropyl cellulose (1-PC) and hydroxypropyl methyl
cellulose (HPMC);
(vi) A natural or synthetic water-insoluble powdered cellulose (CP).
[00216] The aforementioned plaque-biofilm dislodging and removing oral
compositions
can be mixed, absorbed, dispersed, suspended, emulsified or dissolved, to form
a paste,
a gel, a cream, a liquid, a powder, a gum or a solid with carrier ingredients
(C),
comprising the following:
(i) A solid substance, a powder, a flake or a gum, including one or more of
the
following: cellulose, micro-cellulose, hydrated silica, precipitated silica,
amorphous silica, precipitated silica, a silica xerogel, a polyethylene glycol
with a molecular weight above about 650, sorbitol, mannitol, maltitol,
isomalt,
calcium sulfate, gypsum, magnesium sulfate, hydrated magnesium silicate, talc,
sodium bicarbonate, bentonite, sodium carbonate, calcium carbonate, dicalcium
phosphate dihydrate, anhydrous dicalcium phosphate, anhydrous calcium
pyrophosphate, tricalcium phosphate, calcium metaphosphate, a gum base, a
wax, stearic acid;
(ii) From about 0.5% to about 25% ethanol;
(iii) From about 10% to about 95% water;
(iv) From about 5% to about 80% of a humectant selected from glycerin;
sorbitol; 1,2 propylene glycol; 1,3 propanediol; polyethylene glycol with
a molecular weight between 250 and 650; polypropylene glycol;
erythritol; and xylitol.
[00217] An embodiment can be a dentifrice in the form of a toothpaste,
tooth-gel, dental-
cream, tooth-liquid or tooth powder, which maximizes the ability of the
toothbrush or
other suitable applicator to physically remove plaque-biofilm from teeth
during brushing.
Included in dentifrice embodiments are a prophylaxis paste, a prophylaxis gel,
a
prophylaxis powder for in-office stain removal and polishing of teeth by a
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professional. Another dentifrice embodiment is a professionally prescribed or
applied
high fluoride oral gel for patients at high risk of dental caries or who
exhibit signs of
early carious lesions such as white spots.
[00218] A dentifrice composition of these embodiments, may comprise
from about 0.1%
to about 6% of a fibrillated or micro-fibrillated, natural or synthetic, water-
insoluble,
hydratable, polymer (MFC), which swells and thickens in an aqueous medium to
form a
viscoelastic fluid, and which physically removes plaque biofilm from oral
surfaces.
[00219] The dentifrice composition can optionally comprise one or more
of the following
additional plaque-biofilm removing components comprising:
(i) From about 0.1% to about 5% of a particulate, water-insoluble,
micro-crystalline cellulose (MCC) or a particulate water-insoluble
silicified micro-crystalline cellulose (SMCC);
(ii) From about 0.1% to about 5% of a particulate, synthetic cross-
linked Super Absorbent Polymer (SAP), which swells and thickens in an
aqueous medium;
(iii) From about 0.1% to about 5% of a natural, particulate, non-cross-
linked Superabsorbent Polymer (NSAP), which swells and thickens in
an aqueous medium;
(iv) From about 0.1% to about 2% of a water-insoluble, particulate,
nano-crystalline cellulose polymer (CNC), derived, for example, by acid
hydrolysis of natural or synthetic cellulose;
(v) From about 0.1% to about 4% of one or more of a water-soluble,
organic, polymeric, thickener (PT), selected from one or more of the
following: an alkali metal and ammonium salt of a polyacrylic acid, an
alkali metal and ammonium alginate salt, xanthan gum, guar gum,
carrageenan gum, sodium carboxymethyl cellulose (CMC), methyl
cellulose (MC), hydroxymethyl cellulose (HVIC), hydroxyethyl
cellulose HPMC), hydroxyethyl cellulose (HEC,
(vi) From about 0.1% to about 15% of a natural or synthetic water-
insoluble powdered cellulose (CP).
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[00220] In addition, the dentifrice may comprise one or more the
following functional
dentifrice ingredients, which deliver the additional cleaning and oral health
care and
safety benefits expected of a dentifrice composition comprising, (D):
(i) From about 5% to about 65% of an abrasive
(ii) From 0.2% to about 2% of a surfactant selected from sodium
lauryl sulfate, sodium lauroyl sarcosinate, cocamidopropyl betaine and
sodium lauryl sulfoacetate;
(iii) Optionally, a fluoride source, selected from sodium fluoride,
sodium mono-fluorophosphate, stannous fluoride and an amine fluoride,
in an amount to provide from about 0.025% to about 1% of fluoride-
ions;
(iv) Optionally from about 0.5% to 8% of an inorganic thickener
(v) Optionally, from about 0.2% to 0.5% chlorhexidinc gluconatc for
professionally applied or prescribed dentifrices.
[00221] Furthermore, dentifrices and other oral compositions comprise
one or more of the
following auxiliary ingredients (E), which provide an enjoyable experience,
pleasant
aesthetics, and an optimum environment for effectiveness and safety in the
mouth:
(i) From about 0.2% to about 2.5% of a buffer salt to provide a pH
between about 3.5 and 9.5. The exact pH range chosen may depend on
the fluoride source and the needs of other ingredients;
(ii) From about 01% to about 2.0% of a flavoring agent;
(iii) From about 0.05 to about 1% of a sweetener, selected from
saccharin; sodium saccharin, sucralose, aspartame, Stevia, potassium
acesulfame, neotame, thaumatin, sodium cyclamate;
(iv) From about 0.1% to about 2.0% of a preservative;
(v) Sufficient colorant, such as an FD&C dye to impart a desirable
color to the dentifrice; From about 0.2 to about 2.5% of an
opacifier, such as titanium dioxide, to whiten to the dentifrice;
(vi) From about 0.05% to about 1.0% of an emulsifier.
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[00222] The dentifrices may also include one or more of the following
optional
performance broadening agents (F), selected from:
(i) From about 0.1% to about 5% of a tartar control agent selected from
the following: an alkali metal or ammonium complex phosphate salt,
zinc citrate, zinc lactate, zinc chloride, zinc acetate, an alkali metal
gluconate and an ammonium gluconate salt;
(ii) A tooth desensitizing agent selected from about 0.1% to about 7%,
preferably 6%, of potassium nitrate and from about 0.1% to about 3% a
strontium salt and a stannous salt;
(iii) A non-abrasive stain removing agent selected from sodium citrate,
and a complex phosphate salt;
(iii) A non-abrasive stain removing agent selected from sodium citrate,
and a complex phosphate salt.
[00223] Therapeutic dentifrices are intended for in dental-office
application by
professionals, or for prescription, and include prophylaxis pastes, gels,
powders and
subgingival plaque removing compositions. Also included are high fluoride
treatment
gels, which comprise from about 0.15% to about 1.0% fluoride ion, for patients
at high
risk of caries or with signs of early carious lesions. These compositions may
also
comprise one or more of the functional, (D), auxiliary (E) and carrier
ingredients (C)
described above. The presence of a fluoride functional ingredient can be
especially
important in a prophylaxis paste, which tends to be highly abrasive. Fluoride
can
promote remineralization of areas of the enamel or dentin, which may have been
abraded
during the prophylaxis. Additionally, the chlorhexidine gluconate functional
ingredient
may be helpful for subgingival professional plaque removing formulations to
kill any
residual pathological bacteria left behind by the sub-gingival biofilm
dislodging
composition. Chlorhexi dine is not generally recommended for routine use in
OTC (Over
the Counter) conventional toothpastes, because of its tendency to stain teeth
and because
of its potential to promote the formation of resistant bacterial strains when
regularly
employed.
[00224] The dentifrice ingredients comprising, plaque biofilm
dislodging and removing
ingredients, (A) and (B), functional components (D), auxiliary constituents,
(E), and
performance broadening agents, (F), are mixed in a suitable carrier (C), to
form a
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mixture, a suspension, dispersion, an emulsion, partial solution, a solid, a
powder, a
liquid, a paste, a gel, or a cream comprising one or more of the following:
(i) A solid substance, a powder, a flake or a gum, selected from one
or more of the following: cellulose, micro-cellulose, hydrated silica,
precipitated silica, amorphous silica, precipitated silica, a silica xerogel,
a polyethylene glycol with a molecular weight above about 650, sorbitol,
mannitol, maltitol, isomalt, calcium sulfate, gypsum, magnesium sulfate,
hydrated magnesium silicate, talc, sodium bicarbonate, bentonite,
sodium carbonate, calcium carbonate, dicalcium phosphate dihydrate,
anhydrous dicalcium phosphate, anhydrous calcium pyrophosphate,
tricalcium phosphate, calcium metaphosphate, a gum base, a wax, a
stearic acid;
(ii) From about 0.5% to about 25% ethanol
(iii) From about 10% to about 95% water
(iv) From about 5% to about 80% of a humectant selected from
glycerin; sorbitol; 1,2 propylene glycol; 1,3 propanediol; polyethylene
glycol with a molecular weight between 250 and 650; sorbitol;
polypropylene glycol; erythritol; and xylitol, mixed, suspended,
dispersed, emulsified or partially dissolved in a carrier.
Example Compositions
A Professional Prophylaxis Paste for Removal of Plaque Biofilm and Tooth Stain
Composition 1 Composition 2
Ingredient Percent by weight
MFC 1.8 2.0
MCC 1.5 1.2
SAP 0.5 0.5
Carboxymethyl cellulose 1.0 0.3
Carbopol 974 (Polyacrylate) 0.0 0.7
Pumice 35.5 0.0
Magnesium silicate 0.0 32.0
Glycerin 30.0 34.0
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Flavor 0.4 0.5
Sodium Saccharin 0.4 0.4
Monosodium phosphate 1.0 0.9
Disodium phosphate 0.5 0.4
Sodium saccharin 0.4 0.4
Sodium fluoride 2.2 2.2
Water 24.8 20.6
Compositions to Remove Subgingival Biofilm with and without Mild Antimicrobial
Agent
Composition 3Composition 4Composition 5
Ingredient Percent by weight
MF'C 3.5 6.0
1.8
MCC 2.0 2.0
1.5
SAP 1.0 0.5
0.4
Xanthan gum 0.4 0.3
0.0
Carboxymethyl cellulose 0.0 0.5
0.4
Carbopol 974 (Polyacrylate) 0.5 0.5 0.4
Xylitol 15.0 0.0
0.0
Erythritol 0.0 0.0
12.0
1,3 Propanediol 20.0 0.0
0.0
Glycerin 10.0 32.26
35.0
Flavor 0.4 0.5
0.4
Monosodium phosphate 1.0 0.7
0.8
Disodium phosphate 0.5 0.3 0.4
Sodium saccharin 0.4 0.4
0.4
Benzalkonium chloride 0.0 0.04
0.0
Cetylpyridinium chloride 0.0 0.0
0.07
Sodium fluoride 0.24 0.24
0.24
Water 45.06 56.2
50.06
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Ingredient Concentration (%)
MFP SnF2 NaF NaF
Paste Paste Paste Bak
soda
Mincrofibrillated cellulose 1.500 1.700 1.500 0.800
MCC 1.500 1.200 2.500 0.600
SAP 0.000 0.000 0.500 0.200
Hydroxypropyl Methyl 0.500 0.000 0.000 0.000
cellulose
Hydroxyethyl cellulose 0.000 0.250 0.300 0.500
Water 22.040 24.116 28.000 18.000
CMC 0.000 0.000 0.000 0.000
Saccharin 0.100 0.150 0.300 0.600
Sucralose 0.050 0.030 0.040 0.070
Sorbitol (70%) 0.000 0.000 0.000 0.000
Glycerin 25.000 45.000 34.000
19.000
Propylene glycol 15.000 3.000 15.320
0.000
PEG-8 0.000 0.000 0.000 2.000
Sodium bicarbonate 0.000 0.000 0.000
55.490
Dicalcium phosphate 31.000 0.000 0.000 0.000
dihydrate
Sodium citrate 0.000 2.500 0.000 0.000
Citric acid 0.000 0.500 0.000 0.000
Tetrasodium pyrophosphate 0.000 1.800 0.000 0.000
Flavor 0.900 0.900 0.850 1.000
Hydrated silica abrasive 0.000 15.000 14.000 0.000
Hydrated silica thickener 0.000 0.500 0.500 0.000
Titanium di oxide 0.400 0.400 0.250 0.000
Sodium lauryl sulfate 1.250 1.000 0.700 0.500
Sodium lauroyl sarcosinate 0.000 0.000 0.000 1.000
35%
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Cocamidopropyl betaine 0.000 0.000 1.000 0.000
(35%)
Stannous fluoride 0.000 0.454 0.000 0.000
Stannous chloride dihydrate 0.000 1.500 0.000 0.000
Sodium fluoride 0.000 0.000 0.240 0.240
Sodium monofluorophosphate 0.760 0.000 0.000 0.000
Total 100.000 100.000 100.000 100.000
Ingredient Concentration (cYo)
Fluoride Oral-
Whitening freshening Oral Antiplaque
Mouthwash Mouthwash Pre- Oral
Rinse
rinse
Micro-fibrillated cellulose 0.200 0.150 0.200
0.250
Micro-crystalline cellulose 0.400 0.500 0.450
0.300
Hydroxypropyl methyl 0.100 0.000 0,15
0.000
cellulose
Psyllium gum 0.000 0.000 0.150
0.000
Sodium fluoride 0.020 0.000 0.000
0.000
Water 67.800 66.912 76.530 67.030
Alcohol 5.000 0.000 0.000
0.000
Sorbitol 70% 2.830 8.000 0.000
5.000
Glycerin 0.000 20.000 19.500
16.000
Propylene glycol 20.000 3.000 2.000
10.000
Hydrogen peroxide (100%) 2.500 0.000 0.000
0.000
Flavor oils 0.000 0.200 0.200
0.350
Monosodium orthophosphate 0.000 0.000 0.150
0.000
Disodium phosphate 0.000 0.000 0.000
0.000
Citric acid 0.000 0.100 0.000
0.100
Sodium citrate 0.000 0.050 0.000
0.100
Cetyl pyridinium chloride 0.000 0.000 0.000
0.070
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SLS 0.000 0.000 0.300
0.000
Poloxamer 407 0.260 0.400 0.000
0.000
Sodium Saccharin 0.350 0.200 0.250
0.300
Sodium benzoate 0.200 0.050 0.200
0.000
Benzoic acid 0.150 0.130 0.000
0.000
Potassium sorbate 0.000 0.000 0.000
0.300
Sucralose 0.060 0.050 0.070
0.030
Zinc acetate 0.000 0.000 0.000
0.020
Eucalyptol 0.000 0.092 0.000
0.000
Thymol 0.000 0.064 0.000
0.050
Menthol 0.070 0.042 0.000
0.100
Methyl Salicylate 0.060 0.060 0.000
0.000
Total 100.000 100.000 100.000
100.000
B. Functional Oral Care Ingredients
[00225] This section further describes the various functional oral care
ingredients for
dentifrices and other compositions. Other than the polymeric plaque dislodging
ingredients, dentifrice functional ingredients include a dentifrice abrasive,
a fluoridating
agent, a surfactant, an inorganic thickener, an organic thickener, a flavoring
agent, a
sweetener, a pH buffer as well as a component capable of reducing plaque
adhesion, a
tartar control agent, a calcium deposits control agent, a tooth desensitizing
agent, a
whitening agent, a water activity modifier, a preservative, in amount that
provides a
dentifrice benefit. In one dentifrice embodiment, it is preferred to include
the four
following dentifrice ingredients from the aforementioned list:
(a) between about 5% and about 50% of a dentifrice abrasive,
(b) between about 0.1% and about 2.0% of one or more dentifrice surfactants,
(c) between about 0.1% and about 1.0% of a sweetener, and
(d) between about 0.1% and about 2.0% of a flavorant.
[00226] Dentifrice embodiments generally contain between about
0.025% to about 1% by
weight of active fluorine. Dentifrices for regular twice daily home use
typically contain
from about 0.08% to about 0.25% soluble fluorine compound. Prophylaxis pastes,
used
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in the dental office, typically contain from about 0.2% to about 1.0%
fluoride. The
permitted contents for fluoride toothpaste in the USA are identified in Table
1 herein.
Additional Embodiments
[00227] Embodiment compositions may be formulated with the stannous
fluoride system
so that optimal physical removal of plaque biofilm, fluoridation of enamel and
deep
delivery of the SnF2 (or other compounds) at gum-teeth interface can be
achieved. The
subgingival deep delivery of SnF2 can be further enhanced by adjusting the
type and
concentration of surfactants (e.g., SLS) to a higher concentration which may
be about
1.5% if necessary. Not wishing to be bound by an explanation, it is believed
that physical
forces applied by embodiment composition during brushing can further promote
deeper
transport of SnF2 to 3 to 6 mm in the subgingival space between gum and teeth.
This can
be analyzed by using surface analysis techniques (e.g., TOF-SIMS or the like).
In
addition, the high level cleaning provided by embodiment composition is also
believed
to facilitate transport of SnF2 such that more effective fluoridation and
antimicrobial
properties can be delivered in various places. The combined benefits of
embodiment
compositions can result in less caries, tooth decay, lower tooth loss,
stronger enamel and
less gingivitis or periodontitis.
[00228] Embodiment methods and compositions may be targeted to obtain
effective stain
removal from teeth during brushing compared to prior art commercial
toothpastes. It has
been discovered that abrasives such as hydrated silica or other particles
(e.g., calcium
carbonate or the like) can become incorporated and entrapped within the
network
structure of embodiment composition even when said composition becomes diluted
with
saliva or water during brushing, i.e., particles do not separate from the
network structure
upon dilution. Collectively, the solids of the composition including
fibrillated materials,
particulate materials (e g , MCC), abrasives (e g , hydrated silica) and
particulate SAP or
their combinations can form a composite pad that can penetrate, wipe, transfer
and
remove stain from teeth. Here the particles in the composition populate the
surface of the
composition pad (not as a slurry) at some surface density and capture and
remove the
stain as the composition is moved over the surface of teeth by the action of
the brush.
[00229] Accordingly, embodiment compositions may be designed and
tailored to
effectively remove stain from teeth according to a new embodiment method that
is
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different and distinct from commercial toothpaste because in conventional
toothpastes
the toothpaste transforms into a low viscosity slurry by saliva dilution as
described
elsewhere herein. In commercial toothpastes, slurried abrasive particles
separate from
the toothpaste and are dragged over the surface of teeth by brush bristle tips
where the
movement of such particles helps in removing stain as articulated well by
Lewis et al
(Lewis, K., Dwyer-Joyce, K. S., & Pickles, M. J. (2004). Interaction between
toothbrushes and toothpaste abrasive particles in simulated tooth cleaning.
Wear, 257(3-
4), 368-376.). It is believed that embodiment method and composition of the
invention
may provide means to more effectively remove stain from teeth and that the new
mechanism may provide larger contact surface area between the composition and
stained
teeth compared to methods or compositions of prior art.
[00230] Compositions of embodiments may effectively remove tea, coffee
and food stain
from teeth and in this regard they can be used routinely on a daily basis or
less frequently,
for example once a week The compositions can al so be formulated in the form
of
prophylaxis paste or gels that can be used by consumers as necessary for
example once
per week to prevent excessive accumulation of stain. In addition, the
compositions can
be formulated as a prophylaxis paste for used by hygienists in a dental office
setting or
for cleaning dentures or dental appliances. When embodiment compositions are
formulated as toothpastes, they may provide effective control of both stain
and plaque
biofilm as described elsewhere herein.
[00231] Embodiment compositions may be formulated to produce chlorine
dioxide
(C102) during and after tooth brushing or application inside the oral cavity.
Sodium
chlorite or other appropriate precursor of chlorine dioxide can be included in
embodiment
compositions at concentration from about 50 ppm to 1000 ppm or more; the
concentration of precursor can be adjusted to allow for reaction with
cellulose ingredients
during storage. The composition may be adjusted to have a pH above 8.0 to
about 10.5
using an appropriate buffer (e.g., phosphate buffer) to prevent the
degradation of the
chlorine dioxide precursor during shelf storage. Once the embodiment
composition is
applied, the precursor would react with natural acids in the oral cavity to
produce nascent
chlorine dioxide in solution. The produced C102 is expected to be effective
over a wide
range of pH in the mouth, for example between 3.0 to 7.5. The combination of
high-level
plaque biofilm removal found with embodiment composition as demonstrated
elsewhere
herein and the produced C102 may be expected to enhance the following
functions: 1)
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killing organisms that cause biofilm; 2) neutralizing mouth odor as in
halitosis; 3)
enhancing whitening of teeth due to oxidative bleaching; 4) preventing tartar
formation
with routine use; 5) removing previously accumulated tartar. Accordingly,
embodiment
compositions that can deliver C102 may be formulated according to the present
invention. Different dosage form compositions are anticipated, including:
toothpaste;
tooth gels; mouth rinses; mouth pre-rinses; prophylaxis pastes and gels.
"These can be
made available for consumer and professional use. Persons skilled in the art
may vary
concentrations and level of ingredients to make effective C102-producing
compositions
based on the teaching of the present invention.
[00232] Embodiment oral compositions wherein abrasives are incorporated
within the
microstructure of the fibrillated network are disclosed. We discovered that
abrasive silica
particles (or other abrasives such as calcium carbonate) become a part of the
embodiment
composition and that such particles do not separate even at high dilution
levels, as
described elsewhere herein This discovery may provide better stain and biofilm
removal
during cleaning such as during tooth brushing or mouth rinsing. This discovery
may
enable making formulations with different dosage forms (paste, gel, slurry,
pre-rinse,
rinse, etc.) where the abrasive particles are securely held within the
fibrillated entities
without transforming into liquid slurries due to dilution as in the case with
prior art
commercial toothpastes. It is thus feasible to make mouth rinses with a small
concentration of highly fibrillated MFC, wherein abrasive particles are
incorporated
within the fibrillated entities. Such composition may be effective in removing
stain and
biofilm from interproximal spaces, surfaces or teeth, at and below the gum
line. Without
being bound by explanation, it is believed that the flow of abrasive-loaded
fibrillated
entities may create shear forces that can provide cleaning when such entities
flow in the
interproximal space, which would enhance cleaning of these inaccessible areas.
Persons
skilled in the art can manipulate and optimize compositions of various dosage
form to
obtain similar cleaning results based on the teaching of this invention.
[00233] In an embodiment, compositions of the invention may facilitate
more effective
fluoridation of tooth enamel when used regularly or when used in conjunction
with high-
concentration prescription fluoride preparations. Embodiment compositions
would
typically include 0.24% fluoride, which is the FDA recommended dose in the
United
States. It is believed that embodiment compositions may facilitate better
fluoridation of
enamel because such compositions can provide high-level removal of organic
residues
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from teeth surfaces. These organic layers, if they are allowed to remain, may
retard
optimal fluoridation due to diffusional resistance of fluoride ions into the
enamel. In
another scenario, when teeth are brushed regularly with an embodiment
composition and
when the level of cleaning is high, it is believed that upon application of
5000 ppm or
10000 ppm fluoride gel/solution, the rate of uptake and fluoridation may be
enhanced
such that enamel build up and strengthening would be faster and more
effective. Not
wishing to be bound by an explanation, it is believed that regular brushing
with an
embodiment composition along with regular application of therapeutic high
fluoride
level preparation would be effective in repairing weak enamel.
Experimental methods and procedures
[00234] Embodiments of the invention are further described but are in
no way limited by
the Examples described herein. It is useful to first describe procedures that
form the basis
for the Examples.
A. Preparation of biofilms for assessing dental plaque removal effectiveness
[00235] In the work reported here, several types of biofilms were
prepared using
protocols. These are: 1) BBF (build up biofilm); 2) Single-species biofilm;
and 3) Dual-
species biofilm. The bacterial species used to grow biofilms and substrates
used are
provided in Table 2.
[00236] BBF is a form of biofilm representing the fact that biofilm
that has occasional
exposure to conditions and compounds that makes it become tougher and more
difficult
to remove from teeth. Dental biofilm which is not removed with daily brushing
accumulates and then calcify overtime forming Tartar as described herein. BBF
was
found to be especially valuable in the present work for evaluating the removal
effectiveness of plaque biofilm from various surfaces and substrates, and in
comparing
prior art commercial toothpastes and embodiment compositions. For the present
work,
BBF is grown over a period of 8 days, and at several times during preparation
it is
exposed to a low concentration of glutaraldehyde, which imparts crosslinking,
strength
and adhesion. Embodiment BBF has proven to be very useful for in vitro
assessment of
biofilm removal and in the development of embodiment methods and compositions.
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Table 2: Methods for growing in vitro biofilm
BBF Single-species Dual-
species biofilm
biofilm
Organisms E. faecalis (Gram +; S. mutans (Gram +; A.
naeslundii (Gram
used ATCC 29212) ATCC 700610) +; ATCC
12104)
P. aeruginosa S. rails
(Gram +;
(Gram-; ATCC ATCC 9811)
27853)
Growth ATS2015 BHI with 2% THB
medium sucrose
Substrate and PTFE or HA Tube HA discs, PTFE HA discs,
Silicone
Geometry tubing tubing
[00237] BBF preparation method/protocol: A bacterial suspension of 108
CFU/mL was
prepared with Enterococcus faecalis and Pseudomonas aeruginosa cultured on
blood
agar (BA) plates at 37 C in Artificial Test Soil (ATS2015) on Day 1. A pre-
disinfected
3.7 mm Inside Diameter PTFE tubing and pump tubing set up was filled with
bacterial
suspension in AT52015. Both ends were connected to make a closed circuit. The
bacterial suspension was circulated in the tubing by a peristaltic pump at 72
mL/hr at
room temperature. After 48 hours, on Day 3, the bacterial suspension was
drained. The
tubing was rinsed with sterile tap water, fixed with 1:50 diluted
glutaraldehyde for 2 min,
rinsed again with sterile tap water, filled with sterile RO water, and left on
the tray
overnight. On Day 4, the tubing was filled with bacterial suspension and
connected to
the peristaltic pump for 4-hour circulation. Then, the tubing was rinsed,
fixed with 1:50
diluted glutaraldehyde for 2 min, rinsed again, and left overnight. The
procedure of Day
4 was repeated on Day 5 except for the last step. Instead of filling it with
sterile RO water,
the tubing was filled with bacterial suspension and was connected to the
peristaltic pump
for circulation over the weekend. On Day 8, the tubing was drained, rinsed,
fixed with
undiluted glutaraldehyde for 20 min, and rinsed again. This is a modification
of the
published method according to: Alfa M, Ribeiro MM, Da Costa Luciano C, Franca
R,
Olson N, DeGagne P. and Singh H. 2017. A novel polytetrafluoroethylene-channel
model, which simulates low levels of culturable bacteria in buildup biofilm
after repeated
endoscope reprocessing. Gastrointest. Enclose. 86(2).442-451.
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[00238] Single-species dental biofilm preparation method/protocol:
Prior to coating
the hydroxyapatite (HA) discs with pellicle, the HA discs were etched for 60
seconds in
0.12 M HC1, soaked in saturated sodium carbonate for 30 seconds, followed by
60
seconds in 1 % phytic acid. To develop pellicles on the HA discs, the discs
were
suspended in 1.2 % mucin in distilled water at 40 C for 15 min. Next, the
solution was
removed with the discs from the heated solution and then cooled down slowly to
36 'C.
The discs were removed from the solution and dried at 37 C for 30 min. This
cyclic
treatment was repeated for 2 days to properly form pellicles to simulate the
dental biofilm
that normally grow in the mouth in the presence of saliva.
[00239] Streptococcus mutans suspension was prepared by growing single
colony
overnight in brain heart infusion (BHI) broth at 37 C. Overnight grown
culture was
diluted to 1:5 in BHI. The prepared discs were placed in a 12-well plate
filled with 2.5
mL of 2 A) sucrose in diluted S. mutans suspension and were incubated at 37 C
until use.
Every 24 hours, the media was replaced by fresh media This biofilm was
prepared as an
adaptation of: Khosravi Y, Kandukuri RDP, Palmer SR, Gloag ES, Borisov SM,
Starke
EM, Ward MT, Kumar P, De Beer D, Chennu A, and Stoodley P. 2020. Use of an
oxygen
planar optode to assess the effect of high velocity microsprays on oxygen
penetration in
a human dental biofilms in-vitro. BMC Oral Health 20:230.
[00240] Dual-species biofilm preparation methods/protocols: Prior to
coating the HA
discs with pellicle, the discs were etched for 60 sec in 0.12 M HC1, soaked in
saturated
sodium carbonate for 30 sec, followed by 60 sec in 1 % phytic acid. To develop
pellicle
on the HA discs, the discs were suspended in 1.2 % mucin in distilled water at
40 C for
15 min. Next, the solution was removed with the discs from the heat and cooled
down to
36 C slowly. The discs were removed from the solution and dried at 37 C for
30 min.
This cyclic treatment was repeated for 2 days.
[00241] This method was modified from Verkaik et al., 2010.
Streptococcus omits was
cultured on Todd-Hewitt broth (THE, Sigma-Aldrich) aerobically and Actinomyces
naeslundii in Chopped meat broth (Anaerobic systems, CA) under anaerobic
conditions,
both at 37 C. Strains were precultured in an overnight batch culture and
inoculated in a
second culture which was grown for 16 hrs. Bacterial concentrations were
adjusted to
108 CFU/mL in adhesion buffer (2 mM potassium phosphate, 50 mM potassium
chloride,
and 1 mM calcium chloride, pH 6.8) with 20 % growth medium (THE for S. rails
and
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Chopped meat broth for A. naeslundii). Three methods were used to prepare the
dual
species dental biofilm, as follows:
[00242] Method 1: Dual-species grown on HA discs: Prepared discs were
aligned on a
rubber strip and placed in 6 inch manifold connected to inlet and outlet. A
peristaltic
pump was used to flow media for 2.5 mL/min through inlet to manifold to outlet
for
drain. Adhesion buffer was flowed first through the manifold for 30 min. For
dual-species
biofilm development, A. naeshmdii suspension was flowed next for 2 hrs then
the flow
was switched to adhesion buffer for 30 min and to S. oralis suspension for 2
hrs to initiate
co-adhesion. Then the flow was switched to THB and operating until use. All
buffer and
media were kept in water bath at 33 C for entire experiment.
[00243] Method 2: Dual-species grown on HA discs: Prepared discs were
soaked in
adhesion buffer for 15 min. The adhesion buffer was replaced by A. naeslundii
suspension and incubated on a rocker at 37 C for 2 hrs. The discs were soaked
in
adhesion buffer again for 15 min and incubated in S. oralis suspension at 37
'V for 2
hours on the rocker. Finally, the discs were placed in a petri dish filled
with fresh THB
and were incubated on the rocker anaerobically at 37 C until use.
[00244] Method 3: Dual-species biofilm grown in tubes: This method
pertains to
preparation of a dual species biofilm using two organisms known to make dental
plaque
biofilm that was proven to provide a quantitative measure of cleaning teeth
according to
the References cited herein. Streptococcus oralis was cultured in Todd-Hewitt
broth
(THB, Sigma-Aldrich) aerobically and Actinomyces naeslundii was cultured in
Chopped
meat broth (Anaerobe Systems, Morgan Hill, CA) under aerobic conditions; both
were
incubated at 37 C. Strains were pre-cultured in an overnight batch culture
and inoculated
in a second culture which was grown for 16 hrs. 3 ft of PTFE tubing was
connected to 2
ft of silicone tubing to make a closed circuit which was connected to a
peristaltic pump
for circulation The PTFE and silicone tubing was filled with 025 % mucin on
the day
before experiment to form pellicles to mimic and simulate the natural
formation of dental
plaque biofilm in the mouth. On the next day, the mucin solution was drained
and the
tubing set was filled with a second culture of A. naeslundii and fluid was
circulated at
Room Temperature at a flowrate of 3 mL/min. After 1 hr, the second culture of
A.
naeslundii was replaced by a second culture of S. oralis and circulated for 1
hr. The
bacterial suspension was replaced by 0.1 % yeast medium in Brain Heart
Infusion (BHI)
broth. The media was replaced every 24 hrs. The silicone tubing was replaced
after 3
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days due to leakage. After 10 days of circulation, the silicone replacement
tubing was
used for testing biofilm removal using the tube geometry as described
elsewhere herein.
According to this method, the biofilm was developed inside the silicone tubing
by
bacterial transfer taking place due to the action of circulation. The
resulting biofilm was
found to adhere well to the surface of silicone tubing as evidenced by dark
blue staining
after exposing it to a 0.5% solution of methylene blue in water. References
for dual-
species biofilms: (1) Verkaik MJ, Busscher HJ, Rustema-Abbing M, Slomp AM,
Abbas
F, and Van der Mei IIC. 2010. Oral biofilm models for mechanical plaque
removal. Clin.
Oral. Invest. 14:403-409. (2) Gusnaniar, Hizal F, Choi C-H, Sjollema J,
Nuryastuti T,
Rustema-Abbing M, Rozenbaum RT, Van der Mei HC, Busscher HJ, and Wessel SW.
2018. Transmission of monospecies and dual-species biofilms from smooth to
nanopillared surfaces. Appl. Environ. Microbiol. 84(15) e01035-18.
[00245] It has been discovered that the buildup biofilm (BBF) model can
simulate two
forms of challenge biofilm: 1) biofilm plaque that grows and accumulates
during a
regular brushing pattern (e.g., every 12 hours to two days) and 2) older
biofilm plaque
that has transformed into tartar or calculus over longer time (e.g., > 1
week). The first
form (plaque biofilm) can be referred to as "young biofilm," which may be soft
and sticky
and easy to remove with brushing, for example. The second form develops in
areas where
biofilm was not fully removed by routine brushing and then transforms into
tartar. Tartar
contains calcified dead bacteria, and it becomes highly adhering to teeth
surfaces and it
cannot be removed by brush bristles.
[00246] During the process of growing BBF, the bacterial suspension is
circulated in a
tube or is made to flow over a substrate (e.g., hydroxyapatite disc) over a
period of from
4 days (BBF4) to 8 days (BBF8) as detailed under "Methods." As the bacterial
suspension is circulated in a horizontal tubing, some bacteria continually
sediment and
accumulate on the bottom of the tube due to gravity. Over time, the biofilm
that forms
on the tube bottom become stronger and more adherent compared to the biofilm
that
forms on the sides and ceiling of the tube. Because the biofilm is treated
periodically
with a dilute glutaraldehyde solution during the biofilm growth process, the
bottom
biofilm transforms into a deposited structure similar to the tartar or
calculus. The upper
biofilm transforms into a less robust material more representative of plaque
biofilm. The
combination of sedimentation and periodic crosslinking with glutaraldehyde
used to
make BBF can be made to simulate both biofilm plaque and tartar in a single
tube or
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experiment. In an embodiment, BBF made can be used to assess and quantitate
the
removal of both plaque biofilm and tartar by tailoring the age and form of the
biofilm.
Biofilm removal assessment methods are described under Methods.
[00247]
BBF has proven to be an excellent surrogate for dental plaque biofilms
because
it adheres well to various different surfaces including both hydroxyapatite
and polymer
surfaces. Also, BBF has been compared with biofilms made with dental/oral
plaque
organisms was found to provide equivalent biofilm removal results. The dual-
species
dental biofilm was used to validate the methods used to assess the removal
effectiveness
from the surface of hydroxyapatite (which is equivalent to tooth enamel as
described
elsewhere herein).
B. Substrate materials
[00248]
For many experiments about cleaning compositions either for
toothbn.ishing
or for other cleaning applications, the biofilm was grown on the internal
surfaces of
polymeric tubes. In many experiments, the tubes of the test segment were made
of
(Teflon ). This is particularly true for biofilm that is grown from S. mutans
bacteria.
The trade name Teflon frequently refers to polytetrafluoroethylene (PTFE).
However,
there are also two other similar compounds, having similar properties, that
can also be
referred to using the trade name Teflon, namely, Fluorinated Ethylene
Propylene (FEP),
and Perfluoroalkoxyalkane (PFA). Polytetrafluoroethylene is not transparent,
while FEP
is transparent. The use of a transparent tube material, especially if the
biofilm challenge
is stained prior to testing, permits visual observation of the progress of
cleaning while
the cleaning process is occurring, and permits photographic documentation of
the results
of cleaning, after the completion of the cleaning process, without destroying
the tube.
However, for experiments reported herein using Teflon, the material used was
p olyt etra flu oroethylene
[00249]
For some experiments, biofilm was grown on the internal surface of
tubing that
made of silicone rather than Teflon. This was done for growing dual-species
biofilm (A.
naeslundii and S. oralis), which is considered (Verkaik et al) to be a very
good simulant
for assessing biofilm removal in non-contact brushing evaluation. It was found
that this
dual-species biofilm did not adhere to Teflon tubing, but adhered to silicone
tubing
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appropriately for use in testing using the technique of flow through a tube as
described
herein.
[00250] For some experiments, in order to most closely correspond to
toothbrushing, the
substrate used was hydroxyapatite. Hydroxyapatite (a form of calcium
phosphate) is a
ceramic material that is similar to tooth enamel. Hydroxyapatite is
commercially
available from Himed, Old Bethpage, NY. During manufacturing of the
hydroxyapatite
tube, the processing conditions were adjusted to produce a surface that
represents tooth
enamel especially well. Therefore, experimental results involving this
hydroxyapatite
surface are an especially good representation of what happens during
toothbrushing.
Hydroxyapatite is available from this manufacturer in the form of flat discs,
which are
usable like any other discs. In an embodiment we used hydroxyapatite in the
form of
tubes having an inside diameter of approximately 0.25 inch and a length of
approximately
4 inch (100mm) to properly assess the biofilm removal from HA using flow in
the tube
geometry as described herein In regard to tubes, hydroxyapatite tubes are not
flexible
and are not transparent. Nevertheless, because of its chemical similarity to
tooth enamel,
hydroxyapatite in the form of tubes is used for some experiments.
[00251] Properties of biofilm such as adhesion strength depend on the
surface on which
biofilm is grown. Relevant characteristics include not just chemistry but also
topology
and elasticity of the surface. Teflon is smooth and of course has low-friction
and
adhesion-resistant properties. Hydroxyapatite, which is a mineral that mimics
the physics
and surface chemistry of tooth enamel, has a surface that is rougher than
Teflon and is
partially porous. Therefore, the same biofilm growing on two different
surfaces could be
different. Bacteria in the mouth are different bacteria from those used to
grow BBF.
Therefore, BBF on Teflon is not the same as dental plaque on teeth, and the
surfaces are
different (enamel vs. Teflon). However, we found that the results obtained
with BBF
were in agreement with those found with the dual species biofilms grown on
hydroxyapatite discs.
C. Biofilm Removal assessment method using a tube geometry
[00252] Several embodiments of the invention include methods for
assessing biofilm
removal by in vitro methods. The embodiments include: 1) methods of growing
BBF in
tube geometries; 2) methods of growing biofilms in HA tubes; 3) methods for
assessing
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biofilm removal and evaluating the mechanical parameters from flow parameters,
including: pressure drop; shear rate; shear stress; volumetric and linear
velocity and
related parameters; 4) ranking the results based on a removal effectiveness
scale; 5) use
of rheometry with a cone and plate geometry or other geometry to assess and
measure
toothpaste flow-induced biofilm removal from HA discs under defined shear rate
and
shear stress conditions; 6) methods to grow dual-species biofilm and use in
assessing the
effectiveness of biofilm removal with any oral composition, including:
toothpastes/dentifrice; tooth gels; mouth rinses, chewing gum or other dosage
forms as
described elsewhere herein. These embodiments are considered a part of the
present
inventions.
[00253] In experiments described herein, some characterization and
screening of
candidate compositions is performed using flowing the composition through a
round
tube, in which the internal walls are coated with bacterial biofilm or other
contaminant.
Although the luminal tubular geometry is not the same as the geometry of teeth
during
toothbrushing, the tubular geometry has usefulness because it is a standard
and easily
reproducible geometry, and because tubes are readily available commercially.
For such
experiments, as a biological challenge, biofilm is grown on the internal
surface of the
tube using a prescribed protocol using specified bacteria that are purchased
from
commercial suppliers.
[00254] For many experiments about cleaning compositions either for
toothbnishing or
for other cleaning applications, the tubes of the test segment were made of
(Teflon ) or
other composition, for example silicone, acrylic, etc. A typical inside
diameter of such a
tube was 3.7 mm (0.146 inch). For experiments reported herein using Teflon,
the material
used was polytetrafluoroethylene. In the experiments described herein, the
stain typically
used for staining biofilm was methylene blue, or in some cases Crystal Violet,
or Rose
Bengal.
[00255] For tube material that is not transparent, if the biofilm
challenge is stained, it is
possible to make some overall observations during the cleaning process in real
time by
observing the general color of the cleaning composition exiting the tube, as a
function of
time. When there is no longer any presence of the stain color in the cleaning
composition
that exits the tube, that is an indicator that effective cleaning has probably
been
accomplished. Furthermore, for a non-transparent tube, if it is desired to
have
photographic evidence or biological quantitation of the condition of the
luminal surface
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after cleaning (such as by culture or PCR methods), it is possible to cut the
tube open and
perform visual inspection or recovery followed by culturing, although that
entails
destroying the tube.
[00256] For some experiments, in order to most closely correspond to
toothbrushing, the
tube used was a tube made of enamel-like hydroxyapatite.
[00257] We found that the results obtained with BBF were in agreement
with those found
with the dual species biofilms grown on hydroxyapatite discs.
[00258] Experiments were conducted herein to demonstrate that test
results for flow
through a Teflon tube are representative of cleaning a hydroxyapatite surface
or are
representative of toothbrushing. The procedure involved growing a pellicle
film on an
HA disc followed by growing single or dual species biofilm on the pellicle.
This mimics
dental plaque on HA discs, and was found to produce results that were in
agreement with
those obtained with the tube geometry. Removal of biofilm from HA discs was
assessed
using a cone and plate geometry available on the Anton Paar rotational
rheometer. A thin
film of toothpaste was placed on the HA disc and the rotating cone was moved
to touch
the toothpaste and set at a certain distance between the cone (truncated) tip
and the
bottom plate. The toothpaste completely filled the gap between the biofilm
coated plate
and the cone. The cone was rotated for 20 seconds at a certain torque or
rotational speed
and the disc was examined to see if biofilm was removed, as described
elsewhere herein.
[00259] When performing tube flow experiments, the geometry was the
biofilm-coated
interior of a tube of circular cross-section, and various potential oral
compositions were
caused to flow through the lumen of the tube. During such a test, the flowrate
and
pressure drop per unit length of the cleaning composition are often
constrained or
measured. Often the biofilm is stained before performing the test, and any
remaining
biofilm is stained after performing the test.
[00260] Build up biofilm (BBF) was grown inside PTFE or silicone tubes
having a 3.7
mm Inside Diameter. For flow tests, the "test section" was a 2 inch long
segment of this
tubing having BBF or other biofilm type on its internal surface In the
experimental setup,
the 2 inch long BBF test section of 3.7 mm Inside Diameter was flanked at each
end by
1 foot long segments of Tygong tubing having an Inside Diameter of 3.2 mm. The
dental
formulation being evaluated was pumped though the series of tubes: 1 foot
flanking
section, followed by the test section, followed by another 1 foot long
flanking section. In
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some experiments the composition flowing through this test setup was a dental
composition at its nominal concentration. In many experiments, the dental
composition
was diluted with water, usually to 50% of its original concentration, to
represent the
consistency of toothpaste in the mouth during brushing. This dental
composition was
pumped by a syringe pump though the series of tubes at a set flow rate of 20
mL/min
(which corresponds to an average linear velocity of about 3.1 cm/s in the test
section) for
a period of 2 minutes. The pressure drop was measured between the two ends of
flanking
tubing, and a calculation was used to obtain the pressure drop across the test
section,
taking into account the lengths of the flanking tubing segments and the test
section, and
their slightly different inside diameters. Immediately after flow of the
cleaning
composition, 120 mL of rinse water was pumped through the tubes at 90 mL/min.
[00261] At the cleaning composition flow rate of 20 mL/min, the
pressure drop measured
was the total pressure drop for the two flanking sections and the 2-inch long
test section.
We estimate the pressure gradient in the 2 inch long test section from use of
the Hagen
Poiseuille equation for laminar flow in a tube:
AP8/./L0
=
iz-R 4
Assuming applicability of the Hagen Poiseuille equation to this situation, we
can show
that the fraction, f, of the total pressure drop that occurs across the test
section is given
by:
L,
D4
f = 2L 2 L
1 2
DD;.,
where D = tube Inside Dimeter, L = length of section, and subscript "1"
denotes the
flanking tubing segments and subscript "2" denotes the test segment.
Substituting
values of the respective lengths and diameters, we obtain the fraction of the
pressure
drop attributable to the test segment as:
f = 0.045
The fraction has this value because in the present setup, the flanking
sections were
longer than the test section and also had a slightly smaller inside diameter.
Then, the
pressure gradient in the test segment in units of psi/ft becomes:
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0.045AP
¨ = total 0.27Ap0õ/ psi/ft
L -1 test 2
12
where the pressure drop has units of psi and the pressure gradient has units
of psi/ft.
For laminar flow of a Newtonian or non-Newtonian fluid, the shear stress at
the wall of
a circular tube is given by:
R 1A13'
= ¨ ¨
2 L
This equation is used to estimate the shear stress exerted by the flowing
composition at
the tube wall of the test segment.
Using Vavc which is the superficial velocity (volumetric flowrate divided by
cross-
sectional area) and assuming a parabolic velocity profile, it is possible to
calculate the
shear rate at the wall, which is dv/dr at r = R. The result can b estimated
as:
Shear rate at wall, 1/see ¨ 8V
It can be noted that these equations are based on an assumption of laminar
Newtonian
flow. For flow of a non-Newtonian fluid, which is what compositions of
embodiments
of the invention are, this is only an approximation. However, some of the
equations are
valid even for non-Newtonian fluids.
D. Protocols for measuring biofilm that remain after cleaning in a tube
geometry
[00262] Results from flow testing were visually characterized on a
ranking scale. We
designated four cleaning rankings (1 to 4) compared to the positive control
(not cleaned).
1= perfectly clean; no spots remaining at all
2= almost as good as 1; but occasional random blue spots of biofilm remain
3= partial removal of biofilm; some biofilm is removed, some remains
4= less than 5% or 10% removal of biofilm or no removal at all
This ranking was used to evaluate the effectiveness of biofilm removal of the
experimental and to compare prior art commercial toothpaste compositions with
embodiment compositions. This ranking method was used to assess biofilm
removal
from PTFE tubing, from silicone tubing, and from HA tubing. Sometimes this
method
also was extended to evaluate HA discs as described in Examples herein.
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[00263] These ranks were based on visually and microscopically
estimating the "Apparent
Biofilm Removal" based on the fraction of tube surface area where the biofilm
was
removed. To describe the extent of biofilm removal in a slightly more
quantitative
manner, this ranking and the corresponding apparent surface area where the
biofilm was
removed are summarized in Table 3: Figure 3 visually illustrates the rankings
used in the
Examples from actual cleaning experiments.
Table 3
Ranking Apparent % BBF Removal
1 100
2 70 - 99
3 30 - 69
4 1-29
Positive Control 0
[00264] The general procedure includes the following steps: 1)
preparing the biofilm in
tubing as described under Methods; 2) staining the biofilm with the selected
stain (e.g.,
methylene blue); 3) assessing the amount of biofilm in the tube lumen by the
surface area
covered with biofilm or by recovering the biofilm by sonication followed by
culturing or
by PCR (polymerase chain reaction); 4) performing the cleaning with test
composition
as described under Methods; 5) assessing the residual biofilm that remain on
the surface
by measuring the uncleaned fraction of surface area (covered by biofilm) using
image
analysis software as described elsewhere herein, 6) computing percent cleaning
or
biofilm removal by subtracting percent of surface covered by biofilm from 100;
7)
alternatively, assigning a ranking scale to the level of removal based on
visual
appearance. The ranking scale assigned was from 1 to 4 with 1 being 100% clean
and 4
being almost uncleaned, as displayed in Figure 3.
E. Using rotational rheometers to perform and test removal of biofilm from HA
discs
[00265] As described elsewhere herein, rheometcrs arc conventionally
used to measure
rheological properties of materials by placing the materials between two
surfaces, with
there being relative rotation between the two surfaces, with the rotation
being either
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continuous rotation or oscillatory rotation. Here, we used this device to test
the
toothpaste flow-induced bacterial biofilm removal.
[00266] In testing for this example (using an Anton Paar MCR 302
rheometer), we used
a cone-plate geometry. For the bottom disc of the rheometer configuration, we
used an
enamel-like hydroxyapatite disc (from Himed) of 1.2 cm diameter. This disc was
coated
with a biofilm prepared as described elsewhere herein. For the top cone we
used a
roughened metallic cone plate 25 mm in diameter, having a cone angle of 1
degree. We
placed 2m1 of toothpaste on top of the biofilm-coated lower disc, and then we
lowered
the cone to provide the intended gap size. In this configuration, the gap
distance between
the cone and the disc was fixed at about 0.050mm. It can be noted that if the
top and
bottom plates were both perfectly flat and parallel to each other, the local
shear rate would
vary as a function of radius, and cleaning towards the outer part of the disc
would be
better than cleaning near the center. Instead, the conical taper provides a
slightly larger
gap outboard and a smaller gap near the center of the discs. This variation
makes the
local shear rate toward the outside of the disc equal to the local shear rate
near the center
of the disc. (Figure 2) and hence there is a uniform shear rate applied over
the material.
[00267] We then rotated the cone with a predetermined value of either
shear rate, shear
stress, torque or rotational speed. In the case of a constant shear rate, we
kept a constant
shear rate of about 300 s'. The torque was approximately 1.4 mN-m and the
rotational
speed was about 50 rotations/min. Rotation was performed for about 20 seconds.
We
believe these values to be consistent with the typical values experienced
during ordinary
toothbrushing. After the desired rotation, we analyzed the biofilm removal
caused by
composition being tested. We tested the embodiment toothpaste, several other
commercial toothpastes. In most instances, because of interest in the effects
of dilution,
the material being tested was diluted to 50% (or occasionally some other
fraction) of its
nominal or as-purchased composition.
[00268] Representative photographic results of typical experiments are
shown in Figures
4A and 4B. The presence of biofilm is indicated by blue stain. It can be seen
that
formulations of embodiments of the invention (Figure 4B) clearly remove almost
all of
the biofilm from the disc. In contrast, with a commercial toothpaste (Figure
4A), very
little biofilm is removed.
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[00269] We note that the shear rate applied in this test has to be
considered only as an
approximate shear rate value because, due to equipment and specimen
limitations, the
top cone is much larger than the bottom plate, whereas ideally they would be
of the same
size. Nevertheless, this type of experiment provides a very useful set of
data.
F. Image analysis
[00270] Images used in the experimentation were taken with a Firefly
Model GT700 UV
microscope with Bright LED settings (FireflySci Inc., Staten Island, NY). The
images
were taken over the whole surface area of the HA disc Beyond simple visual
observation,
images were inputted to the image processing software ImageJ (public domain,
developed by National Institutes of Health). Images were cropped to exclude
overlapping
sections and portions of the image which did not include the sample. Then the
color
threshold tool under Image > Adjust > Color Threshold, Dark background was
unchecked. Hue, brightness, and saturation were adjusted until the threshold
includes all
the biofilm on the sample. Hue should be selected to be the blue wavelengths,
and
saturation and brightness should include major peaks shown in the diagram
above the
sliders. Then, click select to select all sections with biofilm. To measure,
first, go to
Analyze > Set Measurements and include Area. Then go to Analyze > Measure to
figure
out the number of biofilm-covered pixels. Return to the color thresholding
tool Image >
Adjust > Color Threshold and expand selection to include the whole surface
area of the
HA disc being analyzed. An easy way to do this is after deleting all non-
relevant parts of
the image in the first step (overlapping sections and sections off the sample)
expand hue
and saturation to include the full spectrum and expand brightness from 1 ¨
255. Click
select and this should select the entire sample. Go to Analyze > Measure and
it will print
the number of pixels in the entire section. Repeat this process with each
image until the
entire surface area of the HA disc has been analyzed. Sum the area covered by
biofilm
and sum the total area of each image. The parameter reported as percent
covered is
calculated as covered pixels / total pixels.
G. Rheological measurements
[00271] In experiments described herein, some characterization and
screening of
candidate compositions is performed using measurements of rheology.
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[00272] Rheology describes the behavior of fluids in terms of elastic
behavior and viscous
behavior. These measurements were also taken on the Anton Paar MCR 302
Rheometer,
using an experimental apparatus in which round flat plates rotate relative to
each other.
Rheological measurements characterize a fluid by measuring its viscosity and
by
describing its elastic properties by the Storage Modulus G' and describing its
viscous
properties by its Loss Modulus G" (both having units of Pa or similar units).
[00273] Tribology characterizes the interaction of solid surfaces that
are in relative motion
with respect to other solid surfaces, often with a fluid substance also
present between the
solid surfaces. Such information is relevant to frictional interaction, which
is relevant for
removal of biofilm. Tribological properties can be characterized in terms of
friction
factor, which is a ratio of tangential force to normal force, just as in
classical physics.
This is typically presented in the form of a Stribeck plot, in which the
friction factor is
plotted as a function of relative velocity between the respective solid
surfaces, as is
discussed elsewhere herein
[00274] In the present work, tribological measurements are taken using
an Anton Paar
MCR 302 Rheometer, using an experimental apparatus in which a sphere is
rotated
around a vertical axis while being contacted by smaller pins at three equally
distributed
locations. For some experiments the pins were made of Teflon. For other
experiments
the pins were made of PDMS (polydimethylsiloxane). PDMS is more deformable as
compared to Teflon and this may better reflect the situation of tooth-bristle
interaction
during tooth brushing. It is well known in tribology that the chemistry and
mechanical
properties of the ball and pin surfaces affect friction measurements. It is
thought that the
deformable PDMS pins can better mimic behavior of toothpaste between a hard
surface
(like the tooth enamel) and a softer material (like the bristles of the
toothbrush). We
specifically consider sliding velocities larger than 1 cm/s because such
velocities can
simulate the useful range of velocities encountered during tooth brushing.
[00275] In embodiments of the invention, the rheology is generally
similar to the rheology
of commercial toothpastes.
H. Measurement of Water Activity
[00276] The following is the procedure that was used for measuring
Water Activity. Place
humidity chamber in oven at 23 degrees Celsius and wait for temperature to
stabilize.
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Record initial humidity and temperature readings once temperature has
stabilized. Place
a 5 gram sample in a small glass petri dish at the bottom of humidity chamber.
Secure
fan 8 inches above sample and turn on to highest setting pointing the fan
towards sample.
Record humidity and temperature readings at minutes: 1, 3, 5, 8, 10, 15, and
20. Humidity
stabilizes between 18-20 minutes. Record final humidity reading once
stabilized.
[00277] These procedures and protocols were used in the following
Examples.
Example 1: Dual-species biofilm removal testing¨ embodiment compositions
versus commercial toothpastes, by tube testing
[00278] Dual-species biofilm (A. naeslundii and S. rails) was grown in
silicone tubing
as described elsewhere herein. Verkaik et al found that this biofilm is a
better simulant
for assessing biofilm removal in non-contact brushing evaluation than is S.
mutans
biofilm. Herein, we found that this dual species dental biofilm can provide an
excellent
surrogate biofilm for evaluating embodiment compositions and for providing
valid
comparison with commercial toothpastes.
[00279] CP1 and inventive embodiment TP#46, both at 50% concentration
(diluted with
water), were used as the test composition to determine the effectiveness of
removal of
biofilm after dilution with saliva or water as typically happens during tooth
brushing.
The flow rate and cleaning duration were as described under methods for the
tube
geometry. After coating with biofilm and cleaning according to the experiment,
cross-
sections of the tubes were cut using a razor blade to a length of 1.5-2.0 cm
and then were
bisected horizontally. Samples were analyzed at 10X magnification using a
Leica DMI8
microscope with an HC FL PLAN 10/0.25 Dry objective. Consecutive bright field
images were taken over the entire sample length using the microscope's native
Leica-
1(5-14401188 camera. The biofilm, stained with methylene blue, was identified
visually
as having a blue color under the microscope when viewed via the eyepiece, and
this
corresponds to a dark grey color in the images. ImageJ software was used to
select and
then measure areas covered in biofilm. The biofilm-covered areas were summed
for each
field across the length of the sample, and a total remaining coverage was
determined as
covered area divided by the total area of the tube segment. It was determined
that 36.70%
of the area remained covered by biofilm after cleaning with Commercial
Toothpaste 1
(CP1), whereas only 0.55% of the area remained covered when cleaned with
embodiment
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composition (TP#46). In Figure 5, two images of each sample are shown to
demonstrate
different places on the same sample, showing that biofilm exists over the
whole tube.
The dark grey areas indicate surface covered with biofilm, while black spots
indicate
surface deformities or roughness of the silicone tube. Commercial Toothpaste
images (A
and B) show significant remaining biofilm on the surface of the material in
varying
thickness as well as in shallow and deep roughness and grooves. Images C and
1) show
that TP#46 removed all the biofilm including from surface features while
leaving some
biofilm remaining in the bottom of cracks and crevices.
[00280] The results of this Example clearly show that embodiment
composition (TP#46)
was able to remove 99.45% of the biofilm surface area, compared to 63.3% for
commercial toothpaste CP1. These results are when the dual species biofilm was
used as
the challenge dental biofilm simulant. These (dual species biofilm on a
silicone tube)
results are in agreement with the results obtained with the BBF simulant
biofilm in a
Teflon tube geometry. Figure 5 displays image comparison of TP#46 and CP1
along with
% residual surface area remained covered with biofilm after cleaning.
Example 2: Testing using hydroxyapatite tubes
[00281] Build up biofilm (BBF) was grown on the luminal surface of HA
tubes by the
recirculation method as described under Methods. The removal procedure was
performed
and assessed in the tube geometry by flowing the test compositions inside the
tubing as
described elsewhere herein. The HA material was selected to simulate biofilm
removal
effectiveness with test compositions from teeth enamel and to compare the
results with
BBF was grown on Teflon or silicone tubing or on HA discs. BBF-coated HA tubes
were
stained with methylene blue to the reveal the biofilm and to assess the
removal
effectiveness. Comparison of BBF removal from HA tubing was made with
embodiment
composition (TP#44) and commercial toothpaste CP1 Figure 6 shows that TP#44
was
effective, while commercial toothpaste CP1 was clearly ineffective in removing
BBF
from HA surface. This data is in agreement with other experiments made with
BBF-
coated Teflon and BBF-coated silicone tubing. In addition, these results are
in agreement
with dual-species biofilm removal from HA discs as provided in another Example
herein.
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Example 3: Removal of dual-species biofilm from hydroxyapatite discs under
constant shear stress using the rheometer and methods of quantitation
[00282] Dual-species dental biofilm was grown on HA discs as described
under
"Methods". The biofilm was stained with 0.3% methylene blue (MB) for 10
minutes and
then rinsed with water to remove residual MB and reveal the biofilm before
cleaning.
This served as a control. Removal effectiveness of the dual biofilm was
assessed, with
rotation being performed at constant shear stress using the cone and plate
arrangement
and the configuration as described under "Methods." The cleaning time was 20
seconds.
After this procedure, the HA discs were rinsed with water and then were
evaluated with
special microscopic techniques and image analysis to determine the removal
effectiveness of the dual-species biofilm with either embodiment compositions
or
commercial toothpastes. The surface of HA discs is assessed with image
analysis
software as described elsewhere herein. Percent cleaning was calculated for
the
compositions evaluated. In all cases, the evaluation was made with the
respective
compositions (either commercial toothpastes or embodiments of the invention)
diluted
to 50% of their nominal concentration to simulate the case of dilution with
saliva or water
during tooth brushing, as described elsewhere herein. Results are summarized
in
photographs in Figures 8 and 9.
[00283] Using this process we determined that:
1) This test used dual-species biofilm that was made by shaker wave method.
Commercial toothpaste (CP1) removed only 35.99% of the biofilm (was NOT able
to
remove 64.01% of the biofilm) based on the surface area that remained covered
with
biofilm after cleaning. Percent biofilm removal was 35.99% for CP1.
2) This test used dual-species biofilm that was made with the flow method.
Commercial
toothpaste CP1 removed only 21.44% of the biofilm (was NOT able to remove
78.56%
of the biofilm) based on the surface area of the HA disc.
3.) This test used dual-species biofilm that was made by shaker wave method.
Commercial toothpaste (CP2) removed only 32.06% of the biofilm (was NOT able
to
remove 67.94% of the biofilm) based on the surface area that remained covered
with
biofilm after cleaning. Percent biofilm removal was 32.06% for CP2
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4.) This test used dual-species biofilm that was made with the flow method.
Commercial
toothpaste CP1 removed only 15.45% of the biofilm (was NOT able to remove
84.46%
of the biofilm) based on the surface area of the HA disc.
5) This test used dual-species biofilm that was made with the flow method.
Embodiment
composition (TP75) successfully removed 98.70% of the biofilm on the HA disc.
The
percentage of biofilm that remained was 1.30% of the surface area).
6.) This test used dual-species biofilm that was made with the flow method.
Embodiment
composition TP #75 successfully removed 97.97% of the biofilm on the HA disc.
The
percentage of biofilm that remained was 2.03% of the surface area.
[00284] These results are summarized in Table 4; all test compositions
were at 50%
dilution.
Table 4
Test Test % biofilm
% biofilm
Biofilm Preparation Method
Number Composition Removed
Remaining
1 Shaker CP1 35.99%
64.01%
2 Flow CP1 21.44%
78.56%
3 Shaker CP2 32.06%
67.94%
4 Fl ow CP2 15.45%
84.55%
Shaker TP75 98.70% 1.30%
6 Fl ow TP75 97.97%
2.03%
[00285] The column Biofilm Preparation method indicates the method of
biofilm
generation, as described elsewhere in Methods. The column Composition
indicates the
fluid composition used to clean (after being diluted). The column % Removed
indicates
the fraction of the area on the surface of the HA disc that was NOT covered in
biofilm
after cleaning. The column % remaining indicates the fraction of the area that
remained
covered in biofilm after cleaning, which was the measured quantity in the
test.
[00286] In general, it can be noted that for cleaning with commercial
toothpaste,
significant biofilm remained of the disc generally over the entire surface of
the disc. For
cleaning with toothpastes of embodiments of the invention, whatever small
amount of
biofilm remained was primarily located at the edges of the disc. Biofilm
removal was
about 98% with embodiment compositions at 50% dilution (Table 4)
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Example 4: Head-to-head comparison by taking commercial toothpaste and
adding MFC
[00287] This example shows that pressure drop alone, or corresponding
average wall
shear stress generated during flow, is not a sole determining measure of
cleaning
effectiveness for removing biofilm from surfaces. This Example used Buildup
biofilm
(BBF) that was grown on Teflon tubes as described in Methods.
[00288] In this example, we show that the addition of MFC to commercial
toothpaste
compositions will improve BBF biofilm removal effectiveness of the commercial
composition. Three different brands of popular commercial toothpaste were
tested: CP1,
CP2, and CP3.
[00289] It can be noted that these various commercial toothpastes
comprised a variety of
ingredients including: SLS, sodium lauroyl sarcosinate, Polysorbate 80 (Tween
80),
sodium gluconate, CAPB, SMCT, zinc citrate, Na5P3010, Na21-1PO4, Na01-I,
stannous chloride, carrageenan, xanthan gum, cellulose gum, glycerin, carbomer
(PAA
polyacrylic acid), PEG-8, hydrated silica, TiO2, Mica, sorbitol, sodium
saccharin, and
sucralose. A typical toothpaste can comprise approximately 10 to 12 of these
ingredients
in addition to water.
[00290] The experimental procedure for evaluating the effectiveness of
the cleaning
composition was to dilute it with water to 50% of full strength (thus
replicating a
representative concentration in the mouth during brushing). This mixture was
then
pumped by a syringe pump through tubes of 3.7 mm inside dimeter. The PTFE test
section containing the challenge BBF was 2inch in length and was positioned
between
two flanking tubing segments each of 1 foot length. The flow rate of the
diluted
composition was 20 mL/min for a period of 2 minutes. Pressures were measured
at this
flow rate at the inlet to the first flanking tubing. Cleaning was followed by
a rinse with
water at 90 mL/min for 1.3 minutes.
[00291] As mentioned, the compositions were made at 50% dilution with
water, and the
compositions that did contain MFC contained MFC concentrations of 1% MFC or
0.5%
MFC. Thus, on an undiluted basis the concentrations of MFC in the toothpaste
would
have been 2% or 1%, respectively.
[00292] Results: We did not see any sample that might be ranked as a 3.
For this series of
experiments, Table 5A gives MFC content, ranking results, and pressure drop
across the
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test section and the two 1 foot long flanking segments of tubing, and the
calculated wall
shear stress. A rank of 1 is the best rank while a rank of 4 is the worst. The
visual
appearances of illustrative cleaned test sections and their rankings are shown
in Figure
3.
Table 5A
Composition % Rank Pressure, Estimated
Wall
MFC* psi Shear
Stress, Pa
CP2(50% diluted) modified by 1.0 1 11.5
130
having MFC added to it
CP3(50% diluted) modified by 1.0 1 12.5
141
having MFC added to it
CP1 0.0 2 1.7 19
CP2(50% diluted) modified by 0.5 2 4.9
having MFC added to it
CP1(50% diluted) modified by 1.0 4 12.0
136
having MFC added to it
CP2(50% diluted) modified by 0.0 4 4.5
51
having MFC added to it
*MTV concentration is on a diluted basis
[00293] A typical commercial toothpaste representing prior art (CP2,
see Example 2) was
studied "as is" (i.e., with 0% MFC added) and compared with compositions
having three
concentrations of MFC: 0, 0.5 and 1.0%. In the first three instances of this
example, see
Table 5B, the commercial toothpaste, CP2, was diluted to 50%. This diluted
composition
is typically used to simulate the effectiveness of the compositions after
saliva dilution as
normally happens during brushing. MFC in weight percent was added to the 50%
concentration CP2 base and then mixed to produce a uniform mixture. In the
fourth row
of the Table 5B, another commercial toothpaste, CP4, was diluted only by 25%
(resulting
in 75% CP4 and 25% water) with no added MFC. The results are shown in Table
5B:
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Table 5B
Toothpaste Rank Pressure, Estimated Wall
Shear
Composition MFC* psi Stress,
Pa
CP2 (50% dilution) + 1.0 1 11.5 130
MFC
CP2 (50% dilution) + 0.5 2 4.9 55
MFC
CP2 (50% dilution) 0.0 4 4.5 51
CP4 (25% dilution) 0.0 4 16.0 181
*MFC concentration is on a diluted basis.
[00294] It is concluded that the addition MFC to a known commercial
toothpaste
improves the cleaning effectiveness of that commercial toothpaste. In this,
MFC or other
network-forming ingredient is an important component of the inventive
composition. It
should be noted that all MFC-containing compositions included in Table 5A and
in Table
5B are embodiment compositions and are used here to demonstrate role of the
fibrillated
or network forming material in removing biofilms compared to prior art
commercial
compositions.
[00295] Calculation of the wall shear stress is described elsewhere
herein. This data shows
that although an increase in the wall shear stress can be helpful, it is not
the sole factor
in achieving high cleaning effectiveness. We note the high wall shear stress
generated by
the 75% CP4 (25% dilution) mixture but its poor rank. This relatively 'thick'
composition
gave a high pressure drop and correspondingly high wall shear stress but was
unable to
produce effective removal of the biofilm. This shows that simply generating a
high shear
stress at the wall surface is not necessarily sufficient to remove biofilm. It
is believed that
the combination of the unique properties of MFC, its high surface area, and
its fibril
structure enabling it to reach fine crevices, combine to produce an effective
cleaning
agent/composition.
Example 5: Use of humectants
[00296] This example provides embodiment compositions made with
different
humectants. Variation is achieved by adjusting the type and concentration of
humectants
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within the composition. Water activity is measured as the relative humidity at
equilibrium
in a closed vessel equipped with a recirculating fan, and is considered an
important
property of toothpastes to prevent dryness and bacterial growth. Table 6 shows
that
compositions with different water activity levels can be made by adjusting the
type and
concentration of humectants within the composition, and that other ingredient
normally
does not affect water activity. These results show that using glycerol,
propylene glycol,
sorbitol or their mixtures can provide water activity as low as 0.70. Other
compositions
that include glycerol with either propylene glycol, sorbitol, PEG, xylitol or
erythritol or
with mixture of propylene glycol with either glycerol, sorbitol, PEG, xylitol
or erythritol,
were also made and showed that the desired toothpaste water activity between
0.70 and
0.75 can be achieved. This Example shows that humectant-water carrier liquid
can be
used to make embodiment compositions at any desired water activity without
limitation.
The invention is not meant to be limited to the type of humectant or the
mixture used to
make the composition. In addition, compositions made with water are useful
when
preservatives are included.
Table 6
TP 20 TP 22 TP 28 TP 41
Microfibrillated cellulose (MFC) 1.5 1.5 2.0
1.75
Microcrystalline cellulose (MCC) 1.5 1.5 1.5
2.5
Super Absorbent Polymer (SAP) SCL 0.5 0 0
0.5
Titanium dioxide 0.22 0 0
0.22
Hydrated silica abrasive 19.0 19.0
19.0 19.0
Hydrated silica thickener 4.0 2.0 0
2.0
1,2 Propanediol 24.0 0 40
45.0
Glycerin 5.0 45.0 0
0
Baking Soda 0 0 0
0
Sorbitol (70%) 15.0 0 0
0
Water from Sorbitol 4.5 0 0
0
Water
27.387 31.0 37.50 27.137
Water Activity (Wa) 0.78 0.70
0.75 0.71
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Example 6 Minimal composition, with MFC alone (no particles included), is able
to clean
[00297] A relatively simple embodiment composition (Table 7A)
comprising MFC,
glycerin, surfactant and water was found to effectively remove BBF
(representing plaque
biofilm) with a Cleaning Rank of 1. In this composition, the viscosity and
rheology are
determined mainly by the MFC or fibrillated material. This composition lacks
the
presence of MCC, abrasive silica and thickening silica and polymeric
thickeners.
Nevertheless, it could still thoroughly remove the BBF. This indicated that
the fibrillated
network formed due to MFC can effectively function to provide the necessary
attributes
to remove the biofilm. This demonstrates that MFC is the key ingredient for
the plaque
removal performance and that, if needed, MFC can function as a toothpaste
thickener
instead of inorganic thickener such as silica or organic thickeners which are
typically
used as thickening agents in prior art commercial toothpastes.
[00298] As a control, we show that there is no biofilm removal when a
composition does
not contain MFC, even when adding a high load of silica and MCC.
Table 7A
TV 67
Concentration
(%)
Sodium lauryl sulfate (SLS) 1.0
Microfibrillated cellulose (MFC) 5.0
Microcrystalline cellulose (MCC) 0.0
Super Absorbent Polymer (SAP) 0.0
Titanium dioxide 0.22
Hydrated silica abrasive 0.0
Hydrated silica thickener 0.0
Glycerin 35
Water 58.780
AP (psi) 13.40
Cleaning Rank 1
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[00299] In contrast, a similar composition (Table 7B) containing
no MTV (even though it
did contain MCC and abrasive) did not clean at all (Cleaning Rank 4).
Table 7B
EXAMPLE: TP with No MFC
TP 68
Sodium lauryl sulfate (SLS) 1.0
Microfibrillated cellulose (MFC) 0.0
Microcrystalline cellulose (MCC) 4.0
Super Absorbent Polymer (SAP) 0.0
Titanium dioxide 0.22
Hydrated silica abrasive 25.0
Hydrated silica thickener 5.0
Glycerin 40
Water 24.780
Cleaning Rank 4
Example 7: Effect of MCC
[00300] We prepared toothpaste formulations comprising various
different concentrations
and types of microcrystalline cellulose, and showed that successful biofilm
removing
formulations (cleaning ranking 2) can be achieved with microcrystalline
cellulose
particles of various different sizes and types, such as 50 microns silicified
microcrystalline cellulose (SMCC 50) or microcrystalline cellulose with
particle size 200
microns (PH200) or mixtures of them. The concentration of the MCC or SMCC can
be
adjusted from about 1% to 5% to help in tailoring rheological properties and
cleaning
performance. In addition, this example also demonstrates that successful
biofilm cleaning
formulations can be formulated, in case they are needed, within a broad range
of
thickening silica (0 to 5%) or abrasive silica (10 -25%). (MCC was obtained as
Avicel
PH200, from DuPont Nutrition USA, Inc. (part of DOW), Wilmington, DE. SMCC was
obtained from JRS Pharma LP, Patterson, NY. NatrosolT 250HR CS was obtained
from
Ashland Chemicals, Wilmington, DE.) Note that the number 50 or 200 in the
product
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designation indicates mean particle size in microns. the results are
summarized in Table
8. MCC is helpful but there may also be other ways of achieving good cleaning.
Table 8
TP 72 TP 74 TP 75 TP 76
TP 77
Microfibrillated cellulose (MFC) 2.2 175 175 1 75
1 75
Microcrystalline cellulose (MCC) 2.5 2.5 4.0 5.0
5.0
Titanium dioxide 0.22 0.22 0.22 0.22
0.22
Hydrated silica abrasive 10.0 19.0 5.0 10.0
10.0
Hydrated silica thickener 0.5 2.0 0 0
0
Glycerin 40.0 35 35 40
40
Water 44.580 39.530 54.030 43.030
43.030
AP 5.8 5.4 8.8 3.9
3.9
Rank 2 2 2 2
2
*SMCC * PH * PH *50/50; * PH
MCC Type
50 200 200 SMCC50/PH200 200
Example 8: Effect of Polymeric thickeners
[00301] We prepared MFC-based toothpaste formulations with various
polymeric
thickeners and showed that good bacterial biofilm cleaning performance can be
achieved
when formulating the toothpaste with hydroxyethylcellulose (EEC, Natrosol
250HR
CS), xanthan gum or Carbopol 918. This shows that there is a broad range of
polymeric
thickeners concentration and type, or mixture of thereof, from which to select
to meet
any specific requirement of rheological and cleaning performance. Moreover,
these
formulations can be realized within a broad range of MCC (from 0 to 5%), a
broad range
of thickening silica concentration (from 0 to 5%) and with a broad range of
abrasive silica
concentration (10 to 25%). This, along with other Examples, shows that it is
possible to
make a composition without polymeric thickeners that can still clean. The
compositions
and cleaning rankings are shown in Table 9.
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Table 9
TP 49 TP 54 TP 55
Microfibrillated cellulose (MFC) 1.75 1.20 1.20
Microcrystalline cellulose (MCC) 2.5 2.5 2.5
Titanium dioxide 0.22 0.22 0.22
Hydrated silica abrasive 19.0 15.0 15.0
Hydrated silica thickener 2.0 0.5 0.5
Glycerin 35 35 35
Hydroxyethyl cellulose (HEC) (Natrosol
250 HR CS 0.50 0.50 0
Carboxymethyl cellulose (CMC) 0 0 0
Xanthan Gum 0 0 0.50
Carbopol 0 0 0
Carrageenan 0 0 0
Water 36 537 42 587 42
587
Rank 2 3 3
Example 9: Effect of SAP
[00302] Embodiment compositions comprise SAPs. In this Example, we
prepared
compositions with different types of SAPs. Particulate SAPs are included in
embodiment
compositions to tailor their rheology, retard effect of saliva-induced
dilution of the paste,
enhance the removal of plaque biofilm among other functions as described
elsewhere
herein. Two main types of SAP were used and found to provide successful
compositions
in terms of biofilm removal: i) a surface cross-linked SAP (example: 0-60 SCL
obtained
from Zappa Stewart (Westwood, MA); particle size 2 m to 104 lam or larger);
this is in
the form of plate-like particles that remain as discrete particles which do
not
coalesce/merge into each other when exposed to water and ii) not-surface cross-
linked
one (example: Aqua Keep 10SH-NFC made by Sumitomo Seika, Tokyo, Japan;
particle
size 20-30 microns) where the particles formed in water can at least partially
merge
together. Similarly, Carbopol may be used as an SAP despite their small
particle size
(about 1-10 p.m). SAP-containing embodiment compositions can be made at a
broad
range of concentrations of (0 to 5%) and at a broad range of the other
components, for
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example: MFC (0 to 5%), MCC (0 to 5%), abrasive silica (10 to 25%), thickening
silica
(0 to 5%) and polymeric thickeners (0 to 5%). Table 10 provides example
compositions
made with different SAP types and concentrations.
[00303] We prepared MFC-based toothpaste formulations with different
types and
contents of super absorbent polymers (SAP). SAP can be used as an organic
thickener
within our toothpaste and/or as a bacterial biofilm cleaning adjuvant. Two
main types of
SAP were used and found to provide successful toothpaste formulations in terms
of
bacterial biofilm removal: i) a surface cross-linked SAP (Zappa Stewart 0-60
SCL), that
forms plate-like particles in water that do not merge/compenetrate into each
other and ii)
non-surface cross-linked SAP (Aquakeep 10SH-NFC) in which the particles formed
in
water can at least partially compenetrate each other, similarly to solutions
of Carbopol in
water. These toothpastes can be formulated within a broad range of
concentration of SAP
(0 to 5%) and within a broad range of the other compounds examines, such as
MFC,
MCC (0 to 5%), abrasive silica (10 to 25%), thickening silica (0 to 5%) and
polymeric
thickeners (0 to 5%).
[00304] The compositions and cleaning rankings are shown in Table 10. A
representative
micrograph is shown in Figure 1C.
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Table 10
TP 17 TP 18 TP 31
TP 37 TP 59 TP 60
Sodium lauryl sulfate
(SLS) 0.7 1.0 1.0 1.0 1.0
1.0
Microfibrillated
cellulose (MFC) 1.5 1.5 1.5 1.5 1.3
1.3
Microcrystalline
cellulose (MCC) 1.5 1.5 1.5 3.0 2.0
2.0
Super Absorbent
Polymer (SAP) 0.5 0.5 0.5 1.0
0.50 0.50
Titanium dioxide 0 0 0.22 0.22
0.22 0.22
Hydrated silica
abrasive 19.0 19.0 19.0 19.0
15.0 15.0
Hydrated silica
thickener 4.0 4.0 0 0 0
0
1,2 Propanediol 24.0 24.0 45.0 45.0
0.00 0.00
Glycerin 5.0 5.0 0 0
35.0 35.0
Sorbitol (70%) 15.0 15.0 0 0 0
0
Water from Sorbitol 4.5 4.5 0 0 0
0
Sodium phosphate
monobasic 0 0 0 0
0.25 0.25
Sodium phosphate
dibasic 0 0 0 0
0.25 0.25
Potassium sorbate 0 0 0 0
0.10 0.10
Hydroxyethyl cellulose
(HEC) 0 0 0 0
0.25 0.25
Water 28.8 28.5 30.887 29.387 44.130 44.130
Rank 2 2 1 1 1
1
Not
SAP type SCL SCL SCL SCL
SCL
SCL
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Example 10: Incorporation of abrasives in the microstructural network of the
embodiment composition
[00305] The incoproration of abrasives in the fibrillated
microstructure was found to
significantly strengthen the mechanical properties of the resulting material.
Figure 9
shows a significant increase in G' and G" by about a factor 6 when the
abrasive silica
(Zeodent 113) was increased from 5% and 19%in a suspension/paste of 1.5% MFC
by
weight in water. It is believed that the incorporation of abrasives in the
inventive
composition may enhance the effectiveness in removing plaque biofilm and stain
as
detailed elsewhere herein.
[00306] It is known (Lewis, R., Dwyer-Joyce, R. S., & Pickles, M. J.
(2004). Interaction
between toothbrushes and toothpaste abrasive particles in simulated tooth
cleaning.Wear,
257(3-4), 368-376.) that the mechanism by which abrasive particles remove
stain is by
entrapment and dragging/friction of the particle between the toothbrush
bristles and the
surface of the teeth where the stain is located, while abrasive particles that
do not get
trapped underneath the bristles and are dispersed in solution and do not
contribute any
stain removal. In this regard, we hypothesize that the MFC fibers/fibrils act
as another
possible factor in trappping the abrasive prticles and dragging them over the
stain thus
improving the stain removal.
Example 11: Effect of the humectants on mechanical and microstructural
properties of the formulations
[00307] We note that there are significant effects on the
microstructure and mechanical
properties of the toothpaste according to the liquid carrier that is used.
Indeed, there is a
significant increase in viscosity and elasticity when using a humectant or a
mixture of
humectant and water as compared to the use of water alone. The combined use of
humectant and water contributes an increase in the mechanical properties of
the paste
possibly due to the formation of more extended microstructural network without
the
formation of solvent pockets/voids, which are likely to occur when using only
water as a
solvent.
[00308] It is observed that there is significant difference between
compositions made with
a mostly-water carrier liquid and those made with a mostly-humectant carrier
liquid.
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There are differences in the microscopic appearance, in the Water Activity
Coefficient,
and in the rheology of the compositions.
[00309] In Figure 10 we report the storage (G') and viscous modulus
(G") of three
prototypical toothpastes prepared with either water alone as a solvent or
mixtures of
water and glycerol. The weakening of mechanical properties created by water
dilution of
the paste is less pronounced when using a humectant in combination with water
as
compared to water alone, as highlighted. In Figure 11 we report the linear
viscoelastic
response of the toothpaste, made with three different carrier liquids, after
being diluted
with water to a 50% concentration of the original composition. In other words,
the storage
and viscous modulus of the paste at 50% dilution with water are larger when
using a
humectant as a liquid carrier as compared to water alone as a liquid carrier.
We note that
the water dilution is useful to mimic the change in mechanical properties of
the paste
when it comes in contact with saliva in the mouth.
[00310] Table 11 shows the compositions used.
Table 11
TP 75 TP 75* TP 75**
Sodium saccharin 0.3 0.3
0.3
Sucralose 0.05 0.05
0.05
Sodium fluoride 0.243 0.243
0.243
Sodium lauryl sulfate (SLS) 1.0 1.0
1.0
Peppermint flavor 0.3 0.3
0.3
1Vlicrofibrillated cellulose (MFC) 1.75 1.75
1.75
Microcrystalline cellulose (MCC) 4.0 4.0
4.0
Titanium dioxide 0.22 0.22
0.22
Hydrated silica abrasive 5.0 5.0
5.0
Hydrated silica thickener 0.0 0.0
0.0
Glycerin 35 0
70.787
Sodium phosphate monobasic 0.25 0.25
0.25
Sodium phosphate dibasic 0.25 0.25
0.25
Potassium sorbate 0.10 0.10
0.10
Water
51.537 86.537 15.750
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Example 12: Rheology ranges of composition for toothpaste, prophylaxis paste
etc.
TP46 TP75
Sodium saccharin 0.3 0.3
Sucralose 0.05 0.05
Sodium fluoride 0.243 0.243
Sodium lauryl sulfate (SLS) 1.0 1.0
Peppermint flavor 0.3 0.3
Microfibrillated cellulose (MFC) 1 75 1.75
Microcrystalline cellulose (MCC) 2.5 4.0
Titanium dioxide 0.22 0.22
Hydrated silica abrasive 19.0 5.0
Hydrated silica thickener 2.0 0.0
Glycerin 35 40
Sodium phosphate monobasic 0.25 0.25
Sodium phosphate dibasic 0.25 0.25
Potassium sorbate 0.10 0.10
Distilled water 37.037 46.537
[00311] This example shows that embodiment compositions can be made to
cover a wide
range of theological properties from a paste resembling a prophylaxis paste
(TP46) to a
toothpaste formulation (TP75). This Example also shows the effect of water-
induced
dilution on the rheological properties of the compositions. We used water to
mimic the
effect of saliva-induced dilution on the mechanical properties of the
toothpaste.
[00312] Viscosity as a function of the shear rate for TP46 and TP75 at
100% composition
is provided in Figure 12A. For TP46, the viscosity at the lower shear rates is
about 2
orders of magnitude larger than that of TP75, while at the higher shear rates
there is about
one order of magnitude of difference between the viscosity of the two
formulations.
[00313] Figure 12B displays the shear stress as a function of the shear
rate for the two
compositions at 100% concentrations. Here, the yield shear stress of TP46 is
about 500
Pa while that of TP75 is about 100 Pa. Here, the yield stress is defined as
the minimum
stress by which the shear rates start to be significantly different from zero.
This
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rheological behavior is a characteristic of the inventive compositions where
there is a
nearly constant shear stress (between 100 and 1000 Pa) within a shear rate
range of 1 to
about 100 s-1. This suggests that the microstructure of such compositions does
not break
down in this shear rate range which is relevant to tooth brushing. The yield
stress values
of the TP46 and TP75 were also confirmed by oscillatory shear tests performed
at a fixed
angular frequency of deformation of 10 rad/s varying the oscillatory shear
stress. In the
latter, the stress at which G' crosses G" can be identified as the yield
stress (Figure 12C).
Figure 12D displays the linear viscoelastic response of the two compositions
at 100%
concentration (no dilution). TP46 has a storage modulus of about 50,000 Pa
whereas
TP75 has a storage modulus of about 20,000 Pa.
[00314] Figure 12E shows the viscosity as a function of the shear rate
of the two
compositions after dilution with water to 50% concentration. TP46 and TP75
have a
comparable viscosity values over all the shear rate range investigated.
[00315] Figure 12F indicates that the yield stress of TP46 diluted at
50% with water is
about twice (30 Pa) that of TP75 (15 Pa). We note that the yield stress is
determined by
the stress at which G' crosses G". These results support that the embodiment
compositions preserve a gel-like rheometric response (G' >> G") upon dilution
and
suggest that even at 50% dilution the MFC network is only weakened but is not
broken
down. This Example clearly demonstrates that the rheological properties of the
inventive
compositions can be tailored by adjusting the ingredients concentrations, and
in this
respect the invention may not be limited to the ranges disclosed herein.
[00316] This shows, among other things, that we can formulate a broad
range of
mechanical parameters of the compositions of embodiments of the invention.
Further remarks
[00317] In the work for this patent application, beyond the work in
U.S. Serial No.
17/062,424 and PC T/US2020/054149, we increased humectant concentration,
sometimes to as much as 80% concentration. It is observed that, compared to a
water-
dominated carrier liquid, a high-humectant carrier liquid produces a fiber
morphology
that is more favorable to creating entangled networks, without leaving MFC-
depleted
pockets/voids within the microstructure of the material, which is favorable
for removing
plaque biofilm and other matter. Improved removal of plaque biofilm is
demonstrated.
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We disclose compositions containing "thirsty" SAP. Embodiment compositions
significantly improve removal of plaque biofilm.
[00318] It is believed that because of the more effective cleaning
provided by
embodiments of the invention, the fluoride in toothpastes and related products
may more
effectively reach the dentin and enamel of teeth, with beneficial effect.
[00319] In general, any combination of disclosed features, components,
methods and
steps described herein, that is physically possible, is intended to be within
the scope of
the claims.
[00320] All cited references are incorporated by reference herein.
[00321] Although embodiments have been disclosed, it is not desired to
be limited
thereby. Rather, the scope should be determined only by the appended claims.
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