U.S. patent application number 17/037789 was filed with the patent office on 2021-04-01 for methods of use of oral care compositions comprising hops.
The applicant listed for this patent is The Procter & Gamble Company. Invention is credited to Arif Ali Baig, Tammy K. Baker, Aaron Reed Biesbrock, Samuel James St. John.
Application Number | 20210093551 17/037789 |
Document ID | / |
Family ID | 1000005223814 |
Filed Date | 2021-04-01 |
United States Patent
Application |
20210093551 |
Kind Code |
A1 |
Baig; Arif Ali ; et
al. |
April 1, 2021 |
Methods Of Use Of Oral Care Compositions Comprising Hops
Abstract
Methods of use of oral care compositions comprising hops.
Methods of use of anticavity oral care compositions that are free
of fluoride. Methods of use of anticavity toothpaste comprising
hops. Methods of use of anticavity toothpaste comprising hops that
are free of fluoride. Methods of treatment, reduction, and/or
prevention of caries using an oral care composition comprising
hops, and optionally fluoride free.
Inventors: |
Baig; Arif Ali; (Mason,
OH) ; Baker; Tammy K.; (Cincinnati, OH) ;
Biesbrock; Aaron Reed; (Maineville, OH) ; St. John;
Samuel James; (Cincinnati, OH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The Procter & Gamble Company |
Cincinnati |
OH |
US |
|
|
Family ID: |
1000005223814 |
Appl. No.: |
17/037789 |
Filed: |
September 30, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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62907733 |
Sep 30, 2019 |
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62972109 |
Feb 10, 2020 |
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62907735 |
Sep 30, 2019 |
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62972111 |
Feb 10, 2020 |
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62985451 |
Mar 5, 2020 |
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62907736 |
Sep 30, 2019 |
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62943940 |
Dec 5, 2019 |
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62994893 |
Mar 26, 2020 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/9789 20170801;
A61Q 11/00 20130101 |
International
Class: |
A61K 8/9789 20060101
A61K008/9789; A61Q 11/00 20060101 A61Q011/00 |
Claims
1. A method of treating, reducing, or preventing caries comprising:
(a) dispensing a toothpaste composition onto a toothbrush, (b)
applying the toothpaste composition to the oral cavity for at least
1 minute, and (c) expectorating the toothpaste from the oral
cavity, wherein the toothpaste composition comprises hops and
abrasive.
2. The method of claim 1, wherein the toothpaste composition
comprises anticavity toothpaste.
3. The method of claim 1, wherein the hops comprises hops
extract.
4. The method of claim 3, wherein the hops extract comprises hops
alpha acid, hops beta acid, or combinations thereof.
5. The method of claim 4, wherein the hops extract comprises less
than about 1%, by weight of the extract, of hops alpha acid.
6. The method of claim 1, wherein the abrasive comprises silica
abrasive, calcium abrasive, or combinations thereof.
7. The method of claim 6, wherein the calcium abrasive comprises
calcium carbonate, calcium pyrophosphate, calcium phosphate, or
combinations thereof.
8. The method of claim 1, wherein the toothpaste composition
comprises zinc, tin, or combinations thereof.
9. The method of claim 1, wherein the toothpaste is free of
fluoride.
10. A method of treating, reducing, or preventing caries
comprising: (a) instructing a user to apply a toothpaste
composition to a toothbrush, and (b) instructing the user to apply
the toothpaste composition to an oral cavity of the user, wherein
the toothpaste composition comprises hops and abrasive.
11. The method of claim 10, wherein the method further comprises:
(c) instructing the user to not swallow the toothpaste
composition.
12. The method of claim 10, wherein toothpaste composition is free
of fluoride.
13. The method of claim 10, wherein the toothpaste composition
comprises an anticavity toothpaste.
14. The method of claim 10, wherein the hops comprises hops
extract.
15. The method of claim 14, wherein the hops extract comprises hops
alpha acid, hops beta acid, or combinations thereof.
16. The method of claim 15, wherein the hops extract comprises less
than about 1%, by weight of the extract, of hops alpha acid.
17. The method of claim 10, wherein the abrasive comprises silica
abrasive, calcium abrasive, or combinations thereof.
18. The method of claim 17, wherein the calcium abrasive comprises
calcium carbonate, calcium pyrophosphate, calcium phosphate, or
combinations thereof.
19. The method of claim 10, wherein the oral care composition
comprises zinc, tin, or combinations thereof.
20. A method of treating, reducing, or preventing caries
comprising: (a) applying an oral care composition to an oral
cavity, the oral care composition comprising hops, and (b)
expectorating the oral care composition from the oral cavity.
Description
FIELD OF THE INVENTION
[0001] The present invention is directed to methods of use of oral
care compositions comprising hops. The present invention is
directed to methods of use of anticavity oral care compositions
that are free of fluoride.
BACKGROUND OF THE INVENTION
[0002] Oral care compositions, such as toothpaste and/or dentifrice
compositions, can be applied to the oral cavity to clean and/or
maintain the aesthetics and/or health of the teeth, gums, and/or
tongue. Additionally, many oral care compositions are used to
deliver active ingredients directly to oral care surfaces. For
example, toothpaste compositions can have a fluoride ion source,
such as sodium fluoride, sodium monofluorophosphate, and/or
stannous fluoride, as an anticaries drug. While the effectiveness
and safety of fluoride as an anticaries drug is well established,
many consumers desire other options for anticavity protection.
[0003] Unfortunately, current fluoride-free oral care compositions
do not provide enough, or any, protection from caries due to the
acids produced by bacteria found on the surfaces of teeth. As such,
there is a need for methods of use of oral care compositions that
can be fluoride-free and provide an anticavity benefit.
SUMMARY OF THE INVENTION
[0004] Disclosed herein is a method of treating, reducing, or
preventing caries comprising (a) dispensing a toothpaste
composition onto a toothbrush, (b) applying the toothpaste
composition to the oral cavity for at least 1 minute, and (c)
expectorating the toothpaste from the oral cavity, wherein the
toothpaste composition comprises hops and abrasive.
[0005] Also disclosed herein is a method of treating, reducing, or
preventing caries comprising: (a) instructing a user to apply a
toothpaste composition to a toothbrush, and (b) instructing the
user to apply the toothpaste composition to an oral cavity of the
user, wherein the toothpaste composition comprises hops acid and
abrasive.
[0006] Also disclosed herein is a method of treating, reducing, or
preventing caries comprising: (a) applying an oral care composition
to an oral cavity, the oral care composition comprising hops, and
(b) expectorating the oral care composition from the oral
cavity.
[0007] Also disclosed herein is hops beta acid for use as
medicament, preferably wherein the medicament is an oral care
composition.
[0008] Also disclosed herein is hops for use in anticavity
treatment.
[0009] Also disclosed herein is the use of hops to reduce white
spots in an oral cavity, preferably wherein the white spots in the
oral cavity are on teeth and attributable to caries, cavities,
and/or combinations thereof.
DETAILED DESCRIPTION OF THE INVENTION
[0010] The present invention is directed to method of use of
compositions comprising hops in the treatment of cavities, caries,
gingivitis, and/or combinations thereof. The disclosed compositions
comprising hops can be used in the treatment, reduction, or
prevention of caries.
[0011] Dental caries, or tooth decay, is a breakdown of the teeth
due to the acids made by bacteria. Cavities are caused by the acid
produced by bacteria dissolving the hard tissues of the teeth, such
as enamel, dentin, and/or cementum. The acid is produced by the
bacteria when the bacteria breaks down food debris or sugar on the
tooth's surface.
[0012] Fluoride works by making the tooth's surface less soluble to
the acid produced by the bacteria, "plaque acid." Tooth's enamel is
made from hydroxyapatite (Ca.sub.5(PO.sub.4).sub.3(OH)).
Hydroxyapatite can be dissolved from the enamel at a pH of under
5.5 (demineralization). If hydroxyapatite is demineralized in the
presence of fluoride ions, fluorapatite
(Ca.sub.5(PO.sub.4).sub.3(F)) can remineralize on the surface of a
tooth's enamel. In sum, this process is a replacement of a hydroxyl
(OH) ion with a fluoride (F) ion. Fluorapatite is inherently less
soluble than hydroxyapatite, even under acidic conditions. Thus,
fluoride works as an anticaries drug to make the tooth's surface
more resistant and less soluble to plaque acid.
[0013] While not wishing to being bound by theory, it is believed
that the disclosed oral care compositions have a different
mechanism of action than fluoride ion therapy. In contrast to the
single symptom treatment of fluoride (i.e. treating the result of
plaque acid), the disclosed compositions are believed to have
anticavity activity through a combination of effects that
collectively lead to an anticavity effect. While not wishing to
being bound by theory, it is believed that the disclosed oral care
compositions have an anticavity effect by providing one or more of
the following outcomes: (1) suppressing plaque acid production, (2)
neutralizing plaque acids that are produced, and/or (3) reducing
the solubility of the hydroxyapatite hard tissue surface.
[0014] The suppression of plaque acid production can be
accomplished by providing one or more antibacterial agents to kill
the source of the plaque acid the bacteria itself) and/or providing
one or more biofilm modifiers to disrupt and embed antibacterial
agents within the biofilm matrix.
[0015] Neutralizing the plaque acids can be accomplished by
providing one or more biofilm modifiers to disrupt the biofilm
matrix and/or providing one or more buffering agents to buffer the
produced plaque acid and/or increasing the saturation of calcium
ions on the enamel surface by providing one or more calcium ion
sources.
[0016] Reducing the solubility of the hydroxyapatite hard tissue
surface can be accomplished by providing one or more calcium ion
sources. This can create a supersaturated environment of calcium
and/or phosphate ions around the hydroxyapatite surface, which can
shift the equilibrium of Formula I in favor of remineralization of
hydroxyapatite according to Le Chatelier's principle.
Ca.sub.10(PO.sub.4).sub.6(OH).sub.2.revreaction.10Ca.sup.2++6PO.sub.4.su-
p.3-
Formula I. Hydroxyapatite
[0017] Reducing the solubility of the hydroxyapatite hard tissue
surface can also be accomplished by surface adsorbing metal ions
that slow the dissolution of the enamel by forming an acid
resistant surface layer. This may be accomplished, for example, by
depositing stannous ions on the surface of enamel.
[0018] While each of these mechanisms might not be enough, on its
own, to provide an anticavity benefit equivalent to a therapeutic
dose of fluoride, in combination these mechanisms can provide an
anticavity benefit. As such, the present invention is directed to
compositions and methods of use of the compositions that can be
fluoride-free, yet still provide an anticavity and/or anticaries
benefit.
Definitions
[0019] To define more clearly the terms used herein, the following
definitions are provided. Unless otherwise indicated, the following
definitions are applicable to this disclosure. If a term is used in
this disclosure but is not specifically defined herein, the
definition from the IUPAC Compendium of Chemical Terminology, 2nd
Ed (1997), can be applied, as long as that definition does not
conflict with any other disclosure or definition applied herein, or
render indefinite or non-enabled any claim to which that definition
is applied.
[0020] The term "oral care composition", as used herein, includes a
product, which in the ordinary course of usage, is not
intentionally swallowed for purposes of systemic administration of
particular therapeutic agents, but is rather retained in the oral
cavity for a time sufficient to contact dental surfaces or oral
tissues. Examples of oral care compositions include dentifrice,
toothpaste, tooth gel, subgingival gel, mouth rinse, mousse, foam,
mouth spray, lozenge, chewable tablet, chewing gum, tooth whitening
strips, floss and floss coatings, breath freshening dissolvable
strips, or denture care or adhesive product. The oral care
composition may also be incorporated onto strips or films for
direct application or attachment to oral surfaces.
[0021] "Active and other ingredients" useful herein may be
categorized or described herein by their cosmetic and/or
therapeutic benefit or their postulated mode of action or function.
However, it is to be understood that the active and other
ingredients useful herein can, in some instances, provide more than
one cosmetic and/or therapeutic benefit or function or operate via
more than one mode of action. Therefore, classifications herein are
made for the sake of convenience and are not intended to limit an
ingredient to the particularly stated function(s) or activities
listed.
[0022] The term "orally acceptable carrier" comprises one or more
compatible solid or liquid excipients or diluents which are
suitable for topical oral administration. By "compatible," as used
herein, is meant that the components of the composition are capable
of being commingled without interaction in a manner which would
substantially reduce the composition's stability and/or
efficacy.
[0023] The term "substantially free" as used herein refers to the
presence of no more than 0.05%, preferably no more than 0.01%, and
more preferably no more than 0.001%, of an indicated material in a
composition, by total weight of such composition.
[0024] The term "essentially free" as used herein means that the
indicated material is not deliberately added to the composition, or
preferably not present at analytically detectable levels. It is
meant to include compositions whereby the indicated material is
present only as an impurity of one of the other materials
deliberately added.
[0025] While compositions and methods are described herein in terms
of "comprising" various components or steps, the compositions and
methods can also "consist essentially of" or "consist of" the
various components or steps, unless stated otherwise.
[0026] As used herein, the word "or" when used as a connector of
two or more elements is meant to include the elements individually
and in combination; for example, X or Y, means X or Y or both.
[0027] As used herein, the articles "a" and "an" are understood to
mean one or more of the material that is claimed or described, for
example, "an oral care composition" or "a bleaching agent."
[0028] All measurements referred to herein are made at about
23.degree. C. (i.e. room temperature) unless otherwise
specified.
[0029] Generally, groups of elements are indicated using the
numbering scheme indicated in the version of the periodic table of
elements published in Chemical and Engineering News, 63(5), 27,
1985. In some instances, a group of elements can be indicated using
a common name assigned to the group; for example, alkali metals for
Group 1 elements, alkaline earth metals for Group 2 elements, and
so forth.
[0030] Several types of ranges are disclosed in the present
invention. When a range of any type is disclosed or claimed, the
intent is to disclose or claim individually each possible number
that such a range could reasonably encompass, including end points
of the range as well as any sub-ranges and combinations of
sub-ranges encompassed therein.
[0031] The term "about" means that amounts, sizes, formulations,
parameters, and other quantities and characteristics are not and
need not be exact, but can be approximate and/or larger or smaller,
as desired, reflecting tolerances, conversion factors, rounding
off, measurement errors, and the like, and other factors known to
those of skill in the art. In general, an amount, size,
formulation, parameter or other quantity or characteristic is
"about" or "approximate" whether or not expressly stated to be
such. The term "about" also encompasses amounts that differ due to
different equilibrium conditions for a composition resulting from a
particular initial mixture. Whether or not modified by the term
"about," the claims include equivalents to the quantities. The term
"about" can mean within 10% of the reported numerical value,
preferably within 5% of the reported numerical value.
[0032] The oral care composition can be in any suitable form, such
as a solid, liquid, powder, paste, or combinations thereof. The
oral care composition can be dentifrice, tooth gel, subgingival
gel, mouth rinse, mousse, foam, mouth spray, lozenge, chewable
tablet, chewing gum, tooth whitening strips, floss and floss
coatings, breath freshening dissolvable strips, or denture care or
adhesive product. The components of the dentifrice composition can
be incorporated into a film, a strip, a foam, or a fiber-based
dentifrice composition. The oral care composition can include a
variety of active and inactive ingredients, such as, for example,
but not limited to a hops extract, a tin ion source, a calcium ion
source, water, a fluoride ion source, zinc ion source, one or more
polyphosphates, humectants, surfactants, other ingredients, and the
like, as well as any combination thereof, as described below.
[0033] Section headers are provided below for organization and
convenience only. The section headers do not suggest that a
compound cannot be within more than one section. In fact, compounds
can fall within more than one section. For example, stannous
chloride can be both a tin ion source and a biofilm modifier,
stannous fluoride can be both a tin ion source and a fluoride ion
source, glycine can be an amino acid, a buffering agent, and/or a
biofilm modifier, among numerous other compounds that can fit
amongst several categories and/or sections.
[0034] Humulus lupulus
[0035] The oral care compositions of the present invention can
comprise hops. The hops can comprise at least one hops compound
from Formula I and/or Formula IV. The compound from Formula I
and/or Formula IV can be provided by any suitable source, such as
an extract from Humulus lupulus or Hops, Humulus lupulus itself, a
synthetically derived compound, and/or salts, prodrugs, or other
analogs thereof. The hops extract can comprise one or more hops
alpha acids, one or more hops iso-alpha acids, one or more hops
beta acids, one or more hops oils, one or more flavonoids, one or
more solvents, and/or water. Suitable hops alpha acids (generically
shown in Formula I) can include humulone (Formula II), adhumulone,
cohumulone, posthumulone, prehumulone, and/or mixtures thereof.
Suitable hops iso-alpha acids can include cis-isohumulone and/or
trans-isohumulone. The isomerization of humulone into
cis-isohumulone and trans-isohumulone can be represented by Formula
III.
##STR00001##
[0036] A is the acidic hydroxyl functional group in the alpha
position, B are the acidic hydroxyl functional groups in the beta
position, and R is an alkyl functional group.
##STR00002##
[0037] Suitable hops beta acids can include lupulone, adlupulone,
colupulone, and/or mixtures thereof. A suitable hops beta acid can
include a compound a described in Formula IV, V, VI, and/or
VII.
##STR00003##
[0038] B are the acidic hydroxyl functional groups in the beta
position and R is an alkyl functional group.
##STR00004##
[0039] While hops alpha acids can demonstrate some antibacterial
activity, hops alpha acids also have a bitter taste. The bitterness
provided by hops alpha acids can be suitable for beer, but are not
suitable for use in oral care compositions. In contrast, hops beta
acids can be associated with a higher antibacterial and/or
anticaries activity, but not as bitter a taste. Thus, a hops
extract with a higher proportion of beta acids to alpha acids than
normally found in nature, can be suitable for use in oral care
compositions for use as an antibacterial and/or anticaries
agent.
[0040] A natural hops source can comprise from about 2% to about
12%, by weight of the hops source, of hops beta acids depending on
the variety of hops. Hops extracts used in other contexts, such as
in the brewing of beer, can comprise from about 15% to about 35%,
by weight of the extract, of hops beta acids. The hops extract
desired herein can comprise at least about 35%, at least about 40%,
at least about 45%, from about 35% to about 95%, from about 40% to
about 90%, or from about 45% to about 99%, of hops beta acids. The
hops beta acids can be in an acidic form (i.e. with attached
hydrogen atom(s) to the hydroxl functional group(s)) or as a salt
form.
[0041] A suitable hops extract is described in detail in U.S. Pat.
No. 7,910,140, which is herein incorporated by reference in its
entirety. The hops beta acids desired can be non-hydrogenated,
partially hydrogenated by a non-naturally occurring chemical
reaction, or hydrogenated by a non-naturally occurring chemical
reaction. The hops beta acid can be essentially free of or
substantially free of hydrogenated hops beta acid and/or hops acid.
A non-naturally occurring chemical reaction is a chemical reaction
that was conducted with the aid of chemical compound not found
within Humulus lupulus, such as a chemical hydrogenation reaction
conducted with high heat not normally experienced by Humulus
lupulus in the wild and/or a metal catalyst.
[0042] A natural hops source can comprise from about 2% to about
12%, by weight of the hops source, of hops alpha acids. Hops
extracts used in other contexts, such as in the brewing of beer,
can comprise from about 15% to about 35%, by weight of the extract,
of hops alpha acids. The hops extract desired herein can comprise
less than about 10%, less than about 5%, less than about 1%, or
less than about 0.5%, by weight of the extract, of hops alpha
acids.
[0043] Hops oils can include terpene hydrocarbons, such as myrcene,
humulene, caryophyllene, and/or mixtures thereof. The hops extract
desired herein can comprise less than 5%, less than 2.5%, or less
than 2%, by weight of the extract, of one or more hops oils.
[0044] Flavonoids present in the hops extract can include
xanthohumol, 8-prenylnaringenin, isoxanthohumol, and/or mixtures
thereof. The hops extract can be substantially free of, essentially
free of, free of, or have less than 250 ppm, less than 150 ppm,
and/or less than 100 ppm of one or more flavonoids.
[0045] As described in U.S. Pat. No. 5,370,863, hops acids have
been previously added to oral care compositions. However, the oral
care compositions taught by U.S. Pat. No. 5,370,863 only included
up to 0.01%, by weight of the oral care composition. While not
wishing to be bound by theory, it is believed that U.S. Pat. No.
5,370,863 could only incorporate a low amount of hops acids because
of the bitterness of hops alpha acids. A hops extract with a low
level of hops alpha acids would not have this concern.
[0046] The hops compound can be combined with or free from an
extract from another plant, such as a species from genus Magnolia.
The hops compounds can be combined with or free from triclosan.
[0047] The oral care composition can comprise from about 0.01% to
about 10%, greater than 0.01% to about 10%, from about 0.05%, to
about 10%, from about 0.1% to about 10%, from about 0.2% to about
10%, from about 0.2% to about 10%, from about 0.2% to about 5%,
from about 0.25% to about 2%, from about 0.05% to about 2%, or from
greater than 0.25% to about 2%, of hops, such as hops beta acid, as
described herein. The hops, such as the hops beta acid, can be
provided by a suitable hops extract, the hops plant itself, or a
synthetically derived compound. The hops, such as hops beta acid,
can be provided as neutral, acidic compounds, and/or as salts with
a suitable counter ion, such as sodium, potassium, ammonia, or any
other suitable counter ion.
[0048] The hops can be provided by a hops extract, such as an
extract from Humulus lupulus with at least 35%, by weight of the
extract, of hops beta acid and less than 1%, by weight of the hops
extract, of hops alpha acid. The oral care composition can comprise
0.01% to about 10%, greater than 0.01% to about 10%, from about
0.05%, to about 10%, from about 0.1% to about 10%, from about 0.2%
to about 10%, from about 0.2% to about 10%, from about 0.2% to
about 5%, from about 0.25% to about 2%, from about 0.05% to about
2%, or from greater than 0.25% to about 2%, of hops extract, as
described herein.
Fluoride Ion Source
[0049] The oral care composition can comprise fluoride, such as
from a fluoride ion source. The fluoride ion source can comprise
one or more fluoride containing compounds, such as stannous
fluoride, sodium fluoride, titanium fluoride, calcium fluoride,
calcium phosphate silicate fluoride, potassium fluoride, amine
fluoride, sodium monofluorophosphate, zinc fluoride, and/or
mixtures thereof.
[0050] The fluoride ion source and the tin ion source can be the
same compound, such as for example, stannous fluoride, which can
generate tin ions and fluoride ions. Additionally, the fluoride ion
source and the tin ion source can be separate compounds, such as
when the tin ion source is stannous chloride and the fluoride ion
source is sodium monofluorophosphate or sodium fluoride.
[0051] The fluoride ion source and the zinc ion source can be the
same compound, such as for example, zinc fluoride, which can
generate zinc ions and fluoride ions. Additionally, the fluoride
ion source and the zinc ion source can be separate compounds, such
as when the zinc ion source is zinc phosphate and the fluoride ion
source is stannous fluoride.
[0052] The fluoride ion source can be essentially free of or free
of stannous fluoride. Thus, the oral care composition can comprise
sodium fluoride, potassium fluoride, amine fluoride, sodium
monofluorophosphate, zinc fluoride, and/or mixtures thereof.
[0053] The oral care composition can comprise a fluoride ion source
capable of providing from about 50 ppm to about 5000 ppm, and
preferably from about 500 ppm to about 3000 ppm of free fluoride
ions. To deliver the desired amount of fluoride ions, the fluoride
ion source may be present in the oral care composition at an amount
of from about 0.0025% to about 5%, from about 0.01% to about 10%,
from about 0.2% to about 1%, from about 0.5% to about 1.5%, or from
about 0.3% to about 0.6%, by weight of the oral care composition.
Alternatively, the oral care composition can comprise less than
0.1%, less than 0.01%, be essentially free of, substantially free
of, or free of a fluoride ion source.
Tin Ion Source
[0054] The oral care composition of the present invention can
comprise tin, such as from a tin ion source. The tin ion source can
be any suitable compound that can provide tin ions in an oral care
composition and/or deliver tin ions to the oral cavity when the
dentifrice composition is applied to the oral cavity. The tin ion
source can comprise one or more tin containing compounds, such as
stannous fluoride, stannous chloride, stannous bromide, stannous
iodide, stannous oxide, stannous oxalate, stannous sulfate,
stannous sulfide, stannic fluoride, stannic chloride, stannic
bromide, stannic iodide, stannic sulfide, and/or mixtures thereof.
Tin ion source can comprise stannous fluoride, stannous chloride,
and/or mixture thereof. The tin ion source can also be a
fluoride-free tin ion source, such as stannous chloride.
[0055] The oral care composition can comprise from about 0.0025% to
about 5%, from about 0.01% to about 10%, from about 0.2% to about
1%, from about 0.5% to about 1.5%, or from about 0.3% to about
0.6%, by weight of the oral care composition, of a tin ion
source.
Ca Ion Source
[0056] The oral care composition of the present invention can
comprise calcium, such as from a calcium ion source. The calcium
ion source can be any suitable compound or molecule that can
provide calcium ions in an oral care composition and/or deliver
calcium ions to the oral cavity when the oral care composition is
applied to the oral cavity. The calcium ion source can comprise a
calcium salt, a calcium abrasive, and/or combinations thereof. In
some cases, a calcium salt may also be considered a calcium
abrasive or a calcium abrasive may also be considered a calcium
salt.
[0057] The calcium ion source can comprise a calcium abrasive. The
calcium abrasive can be any suitable abrasive compound that can
provide calcium ions in an oral care composition and/or deliver
calcium ions to the oral cavity when the oral care composition is
applied to the oral cavity. The calcium abrasive can comprise one
or more calcium abrasive compounds, such as calcium carbonate,
precipitated calcium carbonate (PCC), ground calcium carbonate
(GCC), chalk, dicalcium phosphate, calcium pyrophosphate, and/or
mixtures thereof.
[0058] The calcium ion source can comprise a calcium salt, or a
compound that can provide calcium ions in an oral care composition
and/or deliver calcium ions to the oral cavity when the oral care
composition is applied to the oral cavity that can not act as an
abrasive. The calcium salt can comprise one or more calcium
compounds, such as calcium chloride, calcium nitrate, calcium
phosphate, calcium lactate, calcium oxalate, calcium oxide, calcium
gluconate, calcium citrate, calcium bromide, calcium iodate,
calcium iodide, hydroxyapatite, fluorapatite, calcium sulfate,
calcium glycerophosphate, and/or combinations thereof.
[0059] The oral care composition can comprise from about 5% to
about 70%, from about 10% to about 50%, from about 10% to about
60%, from about 20% to about 50%, from about 25% to about 40%, or
from about 1% to about 50% of a calcium ion source.
Buffering Agent
[0060] The oral care composition can comprise a buffering agent.
The buffering agent can be a weak acid or base that can maintain a
particular pH at a selected site in the oral cavity. For example,
the buffering agent can maintain a pH at a tooth's surface to
mitigate the impact of plaque acids produced by bacteria. The
buffering agent can comprise a conjugate acid of an ion also
present in the oral care composition. For example, if the calcium
ion source comprises calcium carbonate, the buffering agent can
comprise a bicarbonate anion (-HCO.sub.3.sup.-). The buffering
agent can comprise a conjugate acid/base pair, such as citric acid
and sodium citrate.
[0061] Suitable buffering systems can include phosphate, citrate
salts, carbonate/bicarbonate salts, a tris buffer, imidazole, urea,
borate, and/or combinations thereof. Suitable buffering agents
include bicarbonate salts, such as sodium bicarbonate, glycine,
orthophosphate, arginine, urea, and or/combinations thereof.
[0062] The oral care composition can comprise from about 1% to
about 30%, from about 5% to about 25% or from about 10% to about
20%, of one or more buffering agents.
Biofilm Modifier
[0063] The oral care composition can comprise one or more biofilm
modifiers. A biofilm modifier can comprise a polyol, an ammonia
generating compound, and/or a glucosyltransferase inhibitor.
[0064] A polyol is an organic compound with more than one hydroxyl
functional groups. The polyol can be any suitable compound that can
weakly associate, interact, or bond to tin ions while the oral care
composition is stored prior to use. The polyol can be a sugar
alcohol, which area class of polyols that can be obtained through
the hydrogenation of sugar compounds with the formula
(CHOH).sub.nH.sub.2. The polyol can be glycerin, erythritol,
xylitol, sorbitol, mannitol, butylene glycol, lactitol, and/or
combinations thereof. The oral care composition can comprise 0.01%
to about 70%, from about 5% to about 70%, from about 5% to about
50%, from about 10% to about 60%, from about 10% to about 25%, or
from about 20% to about 80%, by weight of the oral care
composition, of a polyol.
[0065] The ammonia generating compound can be any suitable compound
that can generate ammonia upon delivery to the oral cavity.
Suitable ammonia generating compounds include arginine, urea,
and/or combinations thereof. The oral care composition can comprise
from about 0.01% to about 10%, from about 1% to about 5%, or from
about 1% to about 25% of one or more ammonia generating
compounds.
[0066] The glucosyltransferase inhibitor can be any suitable
compound that can inhibit a glucosyltransferase.
Glucosyltransferases are enzymes that can establish natural
glycosidic linkages. In particular, these enzymes break down poly-
or oligosaccharide moieties into simple sugars for bacteria
associated with dental caries. As such, any compound that can
inhibit this process can belp prevent dental caries. Suitable
glucosyltransferase inhibitors include oleic acid, epicatechin,
tannins, tannic acid, moenomycin, caspofungin, ethambutol,
lufenuron, and/or combinations thereof. The oral care composition
can comprise from about 0.001% to about 5%, from about 0.01% to
about 2%, or about 1% of one or more glucosyltransferase
inhibitors.
Metal Ion Source
[0067] The oral care composition can comprise metal, such as from a
metal ion source comprising one or more metal ions. The metal ion
source can comprise or be in addition to the tin ion source and/or
the zinc ion source, as described herein. Suitable metal ion
sources include compounds with metal ions, such as, but not limited
to Sn, Zn, Cu, Mn, Mg, Sr, Ti, Fe, Mo, B, Ba, Ce, Al, In and/or
mixtures thereof. The trace metal source can be any compound with a
suitable metal and any accompanying ligands and/or anions.
[0068] Suitable ligands and/or anions that can be paired with metal
ion sources include, but are not limited to acetate, ammonium
sulfate, benzoate, bromide, borate, carbonate, chloride, citrate,
gluconate, glycerophosphate, hydroxide, iodide, oxide, propionate,
D-lactate, DL-lactate, orthophosphate, pyrophosphate, sulfate,
nitrate, tartrate, and/or mixtures thereof.
[0069] The oral care composition can comprise from about 0.01% to
about 10%, from about 1% to about 5%, or from about 0.5% to about
15% of a metal ion source.
Antibacterial Agents
[0070] The oral care composition can comprise one or more
antibacterial agents. Suitable antibacterial agents include any
molecule that provides antibacterial activity in the oral cavity.
Suitable antibacterial agents include hops acids, tin ion sources,
benzyl alcohol, sodium benzoate, menthylglycyl acetate, menthyl
lactate, L-menthol, o-neomenthol, chlorophyllin copper complex,
phenol, oxyquinoline, and/or combinations thereof.
[0071] The oral care composition can comprise from about 0.01% to
about 10%, from about 1% to about 5%, or from about 0.5% to about
15% of an antibacterial agent.
Bioactive Materials
[0072] The oral care composition can also include bioactive
materials suitable for the remineralization of a tooth. Suitable
bioactive materials include bioactive glasses, Novamin.TM.,
Recaldent.TM. hydroxyapatite, one or more amino acids, such as, for
example, arginine, citrulline, glycine, lysine, or histidine, or
combinations thereof. Suitable examples of compositions comprising
arginine are found in U.S. Pat. Nos. 4,154,813 and 5,762,911, which
are herein incorporated by reference in their entirety. Other
suitable bioactive materials include any calcium phosphate
compound. Other suitable bioactive materials include compounds
comprising a calcium source and a phosphate source.
[0073] Amino acids are organic compounds that contain an amine
functional group, a carboxyl functional group, and a side chain
specific to each amino acid. Suitable amino acids include, for
example, amino acids with a positive or negative side chain, amino
acids with an acidic or basic side chain, amino acids with polar
uncharged side chains, amino acids with hydrophobic side chains,
and/or combinations thereof. Suitable amino acids also include, for
example, arginine, histidine, lysine, aspartic acid, glutamic acid,
serine, threonine, asparagine, glutamine, cysteine, selenocysteine,
glycine, proline, alanine, valine, isoleucine, leucine, methionine,
phenylalanine, tyrosine, tryptophan, citrulline, ornithine,
creatine, diaminobutonic acid, diaminoproprionic acid, salts
thereof, and/or combinations thereof.
[0074] Bioactive glasses are comprising calcium and/or phosphate
which can be present in a proportion that is similar to
hydroxyapatite. These glasses can bond to the tissue and are
biocompatible. Bioactive glasses can include a phosphopeptide, a
calcium source, phosphate source, a silica source, a sodium source,
and/or combinations thereof.
[0075] The oral care composition can comprise from about 0.01% to
about 20%, from about 0.1% to about 10%, or from about 1% to about
10% of a bioactive material by weight of the oral care
composition.
Abrasive
[0076] The oral care composition can comprise a calcium abrasive,
as described herein, and/or a non-calcium abrasive, such as
bentonite, silica gel (by itself, and of any structure),
precipitated silica, amorphous precipitated silica (by itself, and
of any structure as well), hydrated silica, perlite, titanium
dioxide, calcium pyrophosphate, dicalcium phosphate dihydrate,
alumina, hydrated alumina, calcined alumina, aluminum silicate,
insoluble sodium metaphosphate, insoluble potassium metaphosphate,
insoluble magnesium carbonate, zirconium silicate, particulate
thermosetting resins and other suitable abrasive materials. Such
materials can be introduced into the oral care compositions to
tailor the polishing characteristics of the target dentifrice
formulation. The oral care composition can comprise from about 5%
to about 70%, from about 10% to about 50%, from about 10% to about
60%, from about 20% to about 50%, from about 25% to about 40%, or
from about 1% to about 50%, by weight of the oral care composition,
of the non-calcium abrasive.
[0077] Alternatively, the oral care composition can be
substantially free of, essentially free of, or free of silica,
alumina, or any other non-calcium abrasive. The oral care
composition can comprise less than about 5%, less than about 1%,
less than about 0.5%, less than about 0.1%, or 0% of a non-calcium
abrasive, such as silica and/or alumina.
Water
[0078] The oral care composition of the present invention can be
anhydrous, a low water formulation, or a high water formulation. In
total, the oral care composition can comprise from 0% to about 99%,
from about 5% to about 75%, about 20% or greater, about 30% or
greater, or about 50% or greater by weight of the composition, of
water. Preferably, the water is USP water.
[0079] In a high water oral care composition and/or toothpaste
formulation, the oral care composition comprises from about 45% to
about 75%, by weight of the composition, of water. The high water
oral care composition and/or toothpaste formulation can comprise
from about 45% to about 65%, from about 45% to about 55%, or from
about 46% to about 54%, by weight of the composition, of water. The
water may be added to the high water formulation and/or may come
into the composition from the inclusion of other ingredients.
[0080] In a low water oral care composition and/or toothpaste
formulation, the oral care composition comprises from about 5% to
about 45%, by weight of the composition, of water. The low water
oral care composition can comprise from about 5% to about 35%, from
about 10% to about 25%, or from about 20% to about 25%, by weight
of the composition, of water. The water may be added to the low
water formulation and/or may come into the composition from the
inclusion of other ingredients.
[0081] In an anhydrous oral care composition and/or toothpaste
formulation, the oral care composition comprises less than about
10%, by weight of the composition, of water. The anhydrous
composition comprises less than about 5%, less than about 1%, or
0%, by weight of the composition, of water. The water may be added
to the anhydrous formulation and/or may come into the composition
from the inclusion of other ingredients.
[0082] A mouth rinse formulation comprises from about 75% to about
99%, from about 75% to about 95%, or from about 80% to about 95% of
water.
[0083] The composition can also comprise other orally acceptable
carrier materials, such as alcohol, humectants, polymers,
surfactants, and acceptance improving agents, such as flavoring,
sweetening, coloring and/or cooling agents.
pH
[0084] The pH of the disclosed composition can be from about 4 to
about 10, from about 7 to about 10, greater than 7 to about 10,
greater than 8 to about 10, greater than 7, greater than 7.5,
greater than 8, greater than 9, or from about 8.5 to about 10.
Zinc Ion Source
[0085] The oral care composition can comprise zinc, such as from a
zinc ion source. The zinc ion source can comprise one or more zinc
containing compounds, such as zinc fluoride, zinc lactate, zinc
oxide, zinc phosphate, zinc chloride, zinc acetate, zinc
hexafluorozirconate, zinc sulfate, zinc tartrate, zinc gluconate,
zinc citrate, zinc malate, zinc glycinate, zinc pyrophosphate, zinc
metaphosphate, zinc oxalate, and/or zinc carbonate. The zinc ion
source can be a fluoride-free zinc ion source, such as zinc
phosphate, zinc oxide, and/or zinc citrate.
[0086] The zinc ion source may be present in the total oral care
composition at an amount of from about 0.01% to about 10%, from
about 0.2% to about 1%, from about 0.5% to about 1.5%, or from
about 0.3% to about 0.6%, by weight of the dentifrice
composition.
Polyphosphates
[0087] The oral care composition can comprise polyphosphate, such
as from a polyphosphate source. A polyphosphate source can comprise
one or more polyphosphate molecules. Polyphosphates are a class of
materials obtained by the dehydration and condensation of
orthophosphate to yield linear and cyclic polyphosphates of varying
chain lengths. Thus, polyphosphate molecules are generally
identified with an average number (n) of polyphosphate molecules,
as described below. A polyphosphate is generally understood to
consist of two or more phosphate molecules arranged primarily in a
linear configuration, although some cyclic derivatives may be
present.
[0088] Preferred polyphosphates are those having an average of two
or more phosphate groups so that surface adsorption at effective
concentrations produces sufficient non-bound phosphate functions,
which enhance the anionic surface charge as well as hydrophilic
character of the surfaces. Preferred in this invention are the
linear polyphosphates having the formula: XO (XPO.sub.3).sub.nX,
wherein X is sodium, potassium, ammonium, or any other alkali metal
cations and n averages from about 2 to about 21. Alkali earth metal
cations, such as calcium, are not preferred because they tend to
form insoluble fluoride salts from aqueous solutions comprising a
fluoride ions and alkali earth metal cations. Thus, the oral care
compositions disclosed herein can be free of, essentially free of,
or substantially free of calcium pyrophosphate.
[0089] Some examples of suitable polyphosphate molecules include,
for example, pyrophosphate tripolyphosphate (n=3),
tetrapolyphosphate (n=4), sodaphos polyphosphate (n=6), hexaphos
polyphosphate (n=13), benephos polyphosphate (n=14),
hexametaphosphate (n=21), which is also known as Glass H.
Polyphosphates can include those polyphosphate compounds
manufactured by FMC Corporation, ICL Performance Products, and/or
Astaris.
[0090] The oral care composition can comprise from about 0.01% to
about 15%, from about 0.1% to about 10%, from about 0.5% to about
5%, from about 1 to about 20%, or about 10% or less, by weight of
the oral care composition, of the polyphosphate source.
Humectants
[0091] The oral care composition can comprise one or more
humectants, have low levels of a humectant, be essentially free of,
be substantially free of, or be free of a humectant. Humectants
serve to add body or "mouth texture" to an oral care composition or
dentifrice as well as preventing the dentifrice from drying out.
Suitable humectants include polyethylene glycol (at a variety of
different molecular weights), propylene glycol, glycerin
(glycerol), erythritol, xylitol, sorbitol, mannitol, butylene
glycol, lactitol, hydrogenated starch hydrolysates, and/or mixtures
thereof. The oral care composition can comprise one or more
humectants each at a level of from 0 to about 70%, from about 5% to
about 50%, from about 10% to about 60%, or from about 20% to about
80%, by weight of the oral care composition.
Surfactants
[0092] The oral care composition can comprise one or more
surfactants. The surfactants can be used to make the compositions
more cosmetically acceptable. The surfactant is preferably a
detersive material which imparts to the composition detersive and
foaming properties. Suitable surfactants are safe and effective
amounts of anionic, cationic, nonionic, zwitterionic, amphoteric
and betaine surfactants.
[0093] Suitable anionic surfactants include, for example, the water
soluble salts of alkyl sulfates having from 8 to 20 carbon atoms in
the alkyl radical and the water-soluble salts of sulfonated
monoglycerides of fatty acids having from 8 to 20 carbon atoms.
Sodium lauryl sulfate (SLS) and sodium coconut monoglyceride
sulfonates are examples of anionic surfactants of this type. Other
suitable anionic surfactants include sarcosinates, such as sodium
lauroyl sarcosinate, taurates, sodium lauryl sulfoacetate, sodium
lauroyl isethionate, sodium laureth carboxylate, and sodium dodecyl
benzene sulfonate. Combinations of anionic surfactants can also be
employed.
[0094] Another suitable class of anionic surfactants are alkyl
phosphates. The surface active organophosphate agents can have a
strong affinity for enamel surface and have sufficient surface
binding propensity to desorb pellicle proteins and remain affixed
to enamel surfaces. Suitable examples of organophosphate compounds
include mono-, di- or triesters represented by the general
structure below wherein Z.sub.1, Z.sub.2, or Z.sub.3 may be
identical or different with at least one being an organic moiety.
Z.sub.1, Z.sub.2, or Z.sub.3 can be selected from linear or
branched, alkyl or alkenyl group of from 1 to 22 carbon atoms,
optionally substituted by one or more phosphate groups; alkoxylated
alkyl or alkenyl, (poly)saccharide, polyol or polyether group.
##STR00005##
Some other agents include alkyl or alkenyl phosphate esters
represented by the following structure:
##STR00006##
wherein R.sub.1 represents a linear or branched, alkyl or alkenyl
group of from 6 to 22 carbon atoms, optionally substituted by one
or more phosphate groups; n and m, are individually and separately,
2 to 4, and a and b, individually and separately, are 0 to 20; Z
and Z may be identical or different, each represents hydrogen,
alkali metal, ammonium, protonated alkyl amine or protonated
functional alkylamine, such as analkanolamine, or a
R--(OCH2)(OCH)-- group. Examples of suitable agents include alkyl
and alkyl (poly)alkoxy phosphates such as lauryl phosphate; PPGS
ceteareth-10 phosphate; laureth-1 phosphate; laureth-3 phosphate;
laureth-9 phosphate; trilaureth-4 phosphate; C.sub.12-18 PEG 9
phosphate: and sodium dilaureth-10 phosphate. The alkyl phosphate
can be polymeric. Examples of polymeric alkyl phosphates include
those containing repeating alkoxy groups as the polymeric portion,
in particular 3 or more ethoxy, propoxy isopropoxy or butoxy
groups.
[0095] Other suitable anionic surfactants are sarcosinates,
isethionates and taurates, especially their alkali metal or
ammonium salts. Examples include: lauroyl sarcosinate, myristoyl
sarcosinate, palmitoyl sarcosinate, stearoyl sarcosinate oleoyl
sarcosinate, or combinations thereof.
[0096] Other suitable anionic surfactants include sodium or
potassium alkyl sulfates, such as sodium lauryl sulfate, acyl
isethionates, acyl methyl isethionates, alkyl ether carboxylates,
acyl alaninates, acyl gulatames, acyl glycinates, acyl
sarconsinates, sodium methyl acyl taurates, sodium laureth
sulfosuccinates, alpha olefin sulfonates, alkyl benze sulfonates,
sodium lauroyl lactylate, sodium laurylglucosides hydroxypropyl
sulfonate, and/or combinations.
[0097] Zwitterionic or amphoteric surfactants useful herein include
derivatives of aliphatic quaternary ammonium, phosphonium, and
Sulfonium compounds, in which the aliphatic radicals can be
straight chain or branched, and one of the aliphatic substituents
contains from 8 to 18 carbon atoms and one contains an anionic
water-solubilizing group, e.g., carboxy, sulfonate, sulfate,
phosphate or phosphonate. Suitable betaine surfactants are
disclosed in U.S. Pat. No. 5,180,577. Typical alkyl dimethyl
betaines include decyl betaine or 2-(N-decyl-N,N-dimethylammonio)
acetate, coco-betaine or 2-(N-coco-N,N-dimethyl ammonio)acetate,
myristyl betaine, palmityl betaine, lauryl betaine, cetyl betaine,
cetyl betaine, stearyl betaine, etc. The amidobetaines can be
exemplified by cocoamidoethyl betaine, cocoamidopropyl betaine
(CADB), and lauramidopropyl betaine. Other suitable amphoteric
surfactants include betaines, sultaines, sodium
laurylamphoacetates, alkylamphodiacetates, and/or combinations
thereof.
[0098] Cationic surfactants useful in the present invention
include, for example, derivatives of quaternary ammonium compounds
having one long alkyl chain containing from 8 to 18 carbon atoms
such as lauryl trimethylammonium chloride; cetyl pyridinium
chloride; cetyl trimethyl-ammonium bromide; cetyl pyridinium
fluoride or combinations thereof.
[0099] Nonionic surfactants that can be used in the compositions of
the present invention include, for example, compounds produced by
the condensation of alkylene oxide groups (hydrophilic in nature)
with an organic hydrophobic compound which may be aliphatic or
alkylaromatic in nature. Examples of suitable nonionic surfactants
can include the Pluronics.RTM. which are poloxamers, polyethylene
oxide condensates of alkyl phenols, products derived from the
condensation of ethylene oxide with the reaction product of
propylene oxide and ethylene diamine, ethylene oxide condensates of
aliphatic alcohols, long chain tertiary amine oxides, long chain
tertiary phosphine oxides, long chain dialkyl sulfoxides and
combinations of such materials. Other suitable non-ionic
surfactants includes alkyl glucamides, alkyl glucosides, and/or
combinations thereof.
[0100] The one or more surfactants can also include one or more
natural and/or naturally derived surfactants. Natural surfactants
can include surfactants that are derived from natural products
and/or surfactants that are minimally or not processed. Natural
surfactants can include hydrogenated, non-hydrogenated, or
partially hydrogenated vegetable oils, olus oil, passiflora
incarnata oil, candelilla cera, coco-caprylate, caprate, dicaprylyl
ether, lauryl alcohol, myristyl myristate, dicaprylyl ether,
caprylic acid, caprylic ester, octyl decanoate, octyl octanoate,
undecane, tridecane, decyl oleate, oleic acid decylester, cetyl
palmitate, stearic acid, palmitic acid, glyceryl stearate,
hydrogenated, non-hydrogenated, or partially hydrogenated vegetable
glycerides, Polyglyceryl-2 dipolyhydroxystearate, cetearyl alcohol,
sucrose polystearate, glycerin, octadodecanol, hydrolyzed,
partially hydrolyzed, or non-hydrolyzed vegetable protein,
hydrolyzed, partially hydrolyzed, or non-hydrolyzed wheat protein
hydrolysate, polyglyceryl-3 diisostearate, glyceryl oleate,
myristyl alcohol, cetyl alcohol, sodium cetearyl sulfate, cetearyl
alcohol, glyceryl laurate, capric triglyceride, coco-glycerides,
lectithin, dicaprylyl ether, xanthan gum, sodium coco-sulfate,
ammonium lauryl sulfate, sodium cocoyl sulfate, sodium cocoyl
glutamate, polyalkylglucosides, such as decyl glucoside, cetearyl
glucoside, cetyl stearyl polyglucoside, coco-glucoside, and lauryl
glucoside, and/or combinations thereof. Natural surfactants can
include any of the Natrue ingredients marketed by BASF, such as,
for example, CegeSoft.RTM., Cetiol.RTM., Cutina.RTM.,
Dehymuls.RTM., Emulgade.RTM., Emulgin.RTM., Eutanol.RTM.,
Gluadin.RTM., 1Lameform.RTM., LameSoft.RTM., Lanette.RTM.,
Monomuls.RTM., Myritol.RTM., Plantacare.RTM., Plantaquat.RTM.,
Platasil.RTM., Rheocare.RTM., Sulfopon.RTM., Texapon.RTM., and/or
combinations thereof.
[0101] Other specific examples of surfactants include sodium lauryl
sulfate, sodium lauryl isethionate, sodium lauroyl methyl
isethionate, sodium cocoyl glutamate, sodium dodecyl benzene
sulfonate, alkali metal or ammonium salts of lauroyl sarcosinate,
myristoyl sarcosinate, palmitoyl sarcosinate, stearoyl sarcosinate
and oleoyl sarcosinate, polyoxyethylene sorbitan monostearate,
isostearate and laurate, sodium lauryl sulfoacetate, N-lauroyl
sarcosine, the sodium, potassium, and ethanolamine salts of
N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine, polyethylene
oxide condensates of alkyl phenols, cocoamidopropyl betaine,
lauramidopropyl betaine, palmityl betaine, sodium cocoyl glutamate,
and the like. Additional surfactants desired include fatty acid
salts of glutamate, alkyl glucoside, salts of taurates, betaines,
caprylates, and/or mixtures thereof. The oral care composition can
also be sulfate free.
[0102] The oral care composition can comprise one or more
surfactants each at a level from about 0.01% to about 15%, from
about 0.3% to about 10%, or from about 0.3% to about 2.5%, by
weight of the oral care composition.
Thickening Agents
[0103] The oral care composition can comprise one or more
thickening agents. Thickening agents can be useful in the oral care
compositions to provide a gelatinous structure that stabilizes the
dentifrice and/or toothpaste against phase separation. Suitable
thickening agents include polysaccharides, polymers, and/or silica
thickeners.
[0104] The thickening agent can comprise one or more
polysaccharides. Some non-limiting examples of polysaccharides
include starch; glycerite of starch; gums such as gum karaya
(sterculia gum), gum tragacanth, gum arabic, gum ghatti, gum
acacia, xanthan gum, guar gum and cellulose gum; magnesium aluminum
silicate (Veegum); carrageenan; sodium alginate; agar-agar; pectin;
gelatin; cellulose compounds such as cellulose, microcrystalline
cellulose, carboxymethyl cellulose, hydroxyethyl cellulose,
hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxymethyl
carboxypropyl cellulose, methyl cellulose, ethyl cellulose, and
sulfated cellulose; natural and synthetic clays such as hectorite
clays; and mixtures thereof.
[0105] Other polysaccharides that are suitable for use herein
include carageenans, gellan gum, locust bean gum, xanthan gum,
carbomers, poloxamers, modified cellulose, and mixtures thereof.
Carageenan is a polysaccharide derived from seaweed. There are
several types of carageenan that may be distinguished by their
seaweed source and/or by their degree of and position of sulfation.
The thickening agent can comprise kappa carageenans, modified kappa
carageenans, iota carageenans, modified iota carageenans, lambda
carrageenan, and mixtures thereof. Carageenans suitable for use
herein include those commercially available from the FMC Company
under the series designation "Viscarin," including but not limited
to Viscarin TP 329, Viscarin TP 388, and Viscarin TP 389.
[0106] The thickening agent can comprise one or more polymers. The
polymer can be a polyethylene glycol (PEG), a polyvinylpyrrolidone
(PVP), polyacrylic acid, a polymer derived from at least one
acrylic acid monomer, a copolymer of maleic anhydride and methyl
vinyl ether, a crosslinked polyacrylic acid polymer, of various
weight percentages of the oral care composition as well as various
ranges of average molecular ranges. Alternatively, the oral care
composition can be free of, essentially free of, or substantially
free of a copolymer of maleic anhydride and methyl vinyl ether.
[0107] The thickening agent can comprise one or more inorganic
thickening agents. Some non-limiting examples of suitable inorganic
thickening agents include colloidal magnesium aluminum silicate,
silica thickeners. Useful silica thickeners include, for example,
include, as a non-limiting example, an amorphous precipitated
silica such as ZEODENT.RTM. 165 silica. Other non-limiting silica
thickeners include ZEODENT.RTM. 153, 163, and 167, and ZEOFREE.RTM.
177 and 265 silica products, all available from Evonik Corporation,
and AEROSIL.RTM. fumed silicas.
[0108] The oral care composition can comprise from 0.01% to about
15%, from 0.1% to about 10%, from about 0.2% to about 5%, or from
about 0.5% to about 2% of one or more thickening agents.
Prenylated Flavonoids
[0109] The oral care composition can comprise prenylated flavonoid.
Flavonoids are a group of natural substances found in a wide range
of fruits, vegetables, grains, bark, roots, stems, flowers, tea,
and wine. Flavonoids can have a variety of beneficial effects on
health, such as antioxidative, anti-inflammatory, antimutagenic,
anticarcinogenic, and antibacterial benefits. Prenylated flavonoids
are flavonoids that include at least one prenyl functional group
(3-methylbut-2-en-1-yl, as shown in Formula VIII), which has been
previously identified to facilitate attachment to cell membranes.
Thus, while not wishing to being bound by theory, it is believed
that the addition of a prenyl group, i.e. prenylation, to a
flavonoid can increase the activity of the original flavonoid by
increasing the lipophilicity of the parent molecule and improving
the penetration of the prenylated molecule into the bacterial cell
membrane. Increasing the lipophilicity to increase penetration into
the cell membrane can be a double-edged sword because the
prenylated flavonoid will tend towards insolubility at high Log P
values (high lipophilicity). Log P can be an important indicator of
antibacterial efficacy.
[0110] As such, the term prenylated flavonoids can include
flavonoids found naturally with one or more prenyl functional
groups, flavonoids with a synthetically added prenyl functional
group, and/or prenylated flavonoids with additional prenyl
functional groups synthetically added.
##STR00007##
[0111] Prenyl Function Group with R Representing the other Portions
of the Molecule
[0112] Other suitable functionalities of the parent molecule that
improve the structure-activity relationship (e.g,. structure-MIC
relationship) of the prenylated molecule include additional
heterocycles containing nitrogen or oxygen, alkylamino chains, or
alkyl chains substituted onto one or more of the aromatic rings of
the parent flavonoid.
[0113] Flavonoids can have a 15-carbon skeleton with at least two
phenyl rings and at least one heterocyclic ring. Some suitable
flavonoid backbones can be shown in Formula IX (flavone backbone),
Formula X (isoflavan backbone), and/or Formula XI (neoflavonoid
backbone).
##STR00008##
[0114] Other suitable subgroups of flavonoids include
anthocyanidins, anthoxanthins, flavanones, flavanonols, flavans,
isoflavonoids, chalcones and/or combinations thereof.
[0115] Prenylated flavonoids can include naturally isolated
prenylated flavonoids or naturally isolated flavonoids that are
synthetically altered to add one or more prenyl functional groups
through a variety of synthetic processes that would be known to a
person of ordinary skill in the art of synthetic organic
chemistry.
[0116] Other suitable prenylated flavonoids can include
Bavachalcone, Bavachin, Bavachinin, Corylifol A, Epimedin A,
Epimedin AI, Epimedin B, Epimedin C, Icariin, Icariside I,
Icariside II, Icaritin, Isobavachalcone, Isoxanthohumol,
Neobavaisoflavone, 6-Prenylnaringenin, 8-Prenylnaringenin,
Sophoraflavanone G, (-)-Sophoranone, Xanthohumol, Quercetin,
Macelignan, Kuraridin, Kurarinone, Kuwanon G, Kuwanon C, Panduratin
A, 6-geranylnaringenin, Australone A, 6,8-Diprenyleriodictyol,
dorsmanin C, dorsmanin F, 8-Prenylkaempferol, 7-O-Methylluteone,
luteone, 6-prenylgenistein, isowighteone, lupiwighteone, and/or
combinations thereof. Other suitable prenylated flavonoids include
cannflavins, such as Cannflavin A, Cannflavin B, and/or Cannflavin
C.
[0117] Preferably, the prenylated flavonoid has a high probability
of having a MIC of less than about 25 ppm for S. aureus, a
gram-positive bacterium. Suitable prenylated flavonoids include
Bavachin, Bavachinin, Corylifol A, Icaritin, Isoxanthohumol,
Neobavaisoflavone, 6-Prenylnaringenin, 8-Prenylnaringenin,
Sophoraflavanone G, (-)-Sophoranone, Kurarinone, Kuwanon C,
Panduratin A, and/or combinations thereof.
[0118] Preferably, the prenylated flavonoid has a high probability
of having a MIC of less than about 25 ppm for E. coli, a
gram-negative bacterium. Suitable prenylated flavonoids include
Bavachinin, Isoxanthohumol, 8-Prenylnaringenin, Sophoraflavanone G,
Kurarinone, Panduratin A, and/or combinations thereof.
[0119] Approximately 1000 prenylated flavonoids have been
identified from plants. According to the number of prenylated
flavonoids reported before, prenylated flavonones are the most
common subclass and prenylated flavanols is the rarest sub-class.
Even though natural prenylated flavonoids have been detected to
have diversely structural characteristics, they have a narrow
distribution in plants, which are different to the parent
flavonoids as they are present almost in all plants. Most of
prenylated flavonoids are found in the following families,
including Cannabaceae, Guttiferae, Leguminosae, Moraceae, Rutaceae
and Umbelliferae. Leguminosae and Moraceae, due to their
consumption as fruits and vegetables, are the most frequently
investigated families and many novel prenylated flavonoids have
been explored. Humulus lupulus of the Cannabaceae include
8-prenylnaringenin and xanthohumol, which can play a role in the
health benefits of beer.
[0120] The prenylated flavonoid can be incorporated through a hops
extract, incorporated in a separately added extract, or added as a
separate component of the oral care compositions disclosed
herein.
[0121] Suitable prenylated flavonoids can have a particular
octanol-water partitioning coefficient. The octanol-water
partitioning coefficient can be used to predict the lipophilicity
of a compound. Without wishing to being bound by theory, it is
believed that compounds that fall within the ranges described
herein will be able to enter and/or disrupt the primarily
hydrophobic phospholipid bilayer that makes of the cell membrane of
microorganisms. Thus, the octanol-water partitioning coefficient
can be correlated to the antibacterial effect of prenylated
flavonoids. Suitable prenylated flavonoids can have a log P of at
least about 2, at least about 4, from about 2 to about 10, from
about 4 to about 10, from about 4 to about 7, or from about 4 to
about 7.
[0122] The oral care composition can comprise at least about
0.001%, from about 0.001% to about 5%, from about 0.01% to about
2%, from about 0.0001% to about 2%, or at least about 0.05% of
prenylated flavonoid.
Other Ingredients
[0123] The oral care composition can comprise a variety of other
ingredients, such as flavoring agents, sweeteners, colorants,
preservatives, buffering agents, or other ingredients suitable for
use in oral care compositions, as described below.
[0124] Flavoring agents also can be added to the oral care
composition. Suitable flavoring agents include oil of wintergreen,
oil of peppermint, oil of spearmint, clove bud oil, menthol,
anethole, methyl salicylate, eucalyptol, cassia, 1-menthyl acetate,
sage, eugenol, parsley oil, oxanone, alpha-irisone, marjoram,
lemon, orange, propenyl guaethol, cinnamon, vanillin, ethyl
vanillin, heliotropine, 4-cis-heptenal, diacetyl,
methyl-para-tert-butyl phenyl acetate, and mixtures thereof.
Coolants may also be part of the flavor system. Preferred coolants
in the present compositions are the paramenthan carboxyamide agents
such as N-ethyl-p-menthan-3-carboxamide (known commercially as
"WS-3") or N-(Ethoxycarbonylmethyl)-3-p-menthanecarboxamide (known
commercially as "WS-5"), and mixtures thereof. A flavor system is
generally used in the compositions at levels of from about 0.001%
to about 5%, by weight of the oral care composition. These
flavoring agents generally comprise mixtures of aldehydes, ketones,
esters, phenols, acids, and aliphatic, aromatic and other alcohols.
Sweeteners can be added to the oral care composition to impart a
pleasing taste to the product.
[0125] Suitable sweeteners include saccharin (as sodium, potassium
or calcium saccharin), cyclamate (as a sodium, potassium or calcium
salt), acesulfame-K, thaumatin, neohesperidin dihydrochalcone,
ammoniated glycyrrhizin, dextrose, levulose, sucrose, mannose,
sucralose, stevia, and glucose.
[0126] Colorants can be added to improve the aesthetic appearance
of the product. Suitable colorants include without limitation those
colorants approved by appropriate regulatory bodies such as the FDA
and those listed in the European Food and Pharmaceutical Directives
and include pigments, such as TiO.sub.2, and colors such as
FD&C and D&C dyes.
[0127] Preservatives also can be added to the oral care
compositions to prevent bacterial growth. Suitable preservatives
approved for use in oral compositions such as methylparaben,
propylparaben, benzoic acid, and sodium benzoate can be added in
safe and effective amounts.
[0128] Titanium dioxide may also be added to the present
composition. Titanium dioxide is a white powder which adds opacity
to the compositions. Titanium dioxide generally comprises from
about 0.25% to about 5%, by weight of the oral care
composition.
[0129] Other ingredients can be used in the oral care composition,
such as desensitizing agents, healing agents, other caries
preventative agents, chelating/sequestering agents, vitamins, amino
acids, proteins, other anti-plaque/anti-calculus agents,
opacifiers, antibiotics, anti-enzymes, enzymes, pH control agents,
oxidizing agents, antioxidants, and the like.
Methods of Use
[0130] The oral care compositions of the present invention can be
used in the treatment, reduction, and/or prevention of caries,
cavities, gingivitis, and/or combinations thereof.
[0131] The oral care compositions useful for the methods include
hops, as described above, such as hops provided from a hops extract
and/or an extract of Humulus lupulus. As described herein hops beta
acid can be useful as an anticavity agent. Thus, the addition of
hops to any oral care composition can provide anticavity
protection.
[0132] The oral care composition can include primary packaging,
such as a tube, bottle, and/or tub, The primary package can be
placed within secondary package, such as a carton, shrink wrap, or
the like. Instructions for use of the oral care composition can be
printed on the primary package and/or the secondary package. The
scope of the method is intended to include instructions provided by
a manufacturer, distributor, and/or producer of the oral care
composition.
[0133] If the oral care composition is a toothpaste, the user can
be instructed to dispense the toothpaste from the toothpaste
tube.
[0134] The user can be instructed. to apply a portion of the
toothpaste onto a toothbrush. The portion of the toothpaste can be
of any suitable shape, such as strip, a pea-sized amount, or
various other shapes that would fit onto any mechanical and/or
manual brush head. The user can be instructed to apply a strip of
the toothpaste that is at least about 1 inch, at least about 0.5
inch, at least 1 inch, and/or at least 0.5 inch long to the
bristles of a toothbrush, such as soft-bristled toothbrush.
[0135] The user can be instructed to apply pea-sized or grain of
rice-sized portion of the toothpaste to the bristles of a
toothbrush, such as in the case of use by children of less than 6
years old and/or less than 2 years old.
[0136] The user can be instructed to brush their teeth for at least
about 30 seconds, at least about 1 minute, at least about 90
seconds, at least about 2 minutes, at least 30 seconds, at least 1
minute, at least 90 seconds, and/or at least 2 minutes.
[0137] The user can be instructed to brush their teeth thoroughly
and/or as directed by a physician and/or dentist.
[0138] The user can be instructed to brush their teeth after each
meal. The user can be instructed to brush their teeth at least once
per day, at least twice per day, and/or at least three times per
day. The user can be instructed to brush their teeth no more than
three times a day, such as to prevent Sn staining. The user can be
instructed to brush their teeth in the morning and/or in the
evening prior to sleeping.
[0139] The user can be instructed to not swallow the toothpaste
composition due to the inclusion of ingredients that are not
suitable for ingestion, such as fluoride. However, in the case of
an oral care composition comprising hops, but free of fluoride, the
user may not need to be instructed to not swallow the toothpaste.
The user may be instructed to expectorate (or spit out) the
toothpaste composition after the cessation of the brushing
cycle.
[0140] If the oral care composition is a mouth rinse, the user can
be instructed to dispense the mouth rinse from a bottle containing
the mouth rinse.
[0141] The user can be instructed to use the mouth rinse at least
once a day, at least twice a day, and/or at least three times a
day.
[0142] The user can be instructed to use the mouth rinse
composition after the use of toothpaste and/or floss.
[0143] The user can be instructed to swish a portion of rinse in
the oral cavity, such as between ti re teeth, for a period of time.
The user can be instructed to vigorously swish a portion of the
rinse.
[0144] The user can be instructed to use be from about 5 mL to
about 50 mL, from about 10 mL to about 40 mL, 10 mL, 20 mL, 25 mL,
30 mL, 40 mL, 2 teaspoonfuls, and/or 4 teaspoonfuls of mouth
rinse.
[0145] The user can be instructed to swish the mouth rinse for at
least about 30 seconds, at least about 1 minute, at least about 90
seconds, at least about 2 minutes, at least 30 seconds, at least 1
minute, at least 90 seconds, and/or at least 2 minutes.
[0146] The user can be instructed to not swallow the mouth rinse
composition due to the inclusion of ingredients that are not
suitable for ingestion, such as fluoride. However, in the case of
an oral care composition comprising hops, but free of fluoride, the
user may not need to be instructed to not swallow the mouth rinse.
The user may be instructed to expectorate (or spit out) the mouth
rinse composition after the cessation of the rinse cycle.
[0147] The usage instructions for the oral care composition, such
as for a toothpaste composition and/or a mouth rinse composition,
can vary based on age. For example, adults and children that are at
least 6 or at least 2 can have one usage instruction while children
under 6 or under 2 can have a second usage instruction.
[0148] The oral care composition comprising hops, as described
herein, can be useful as medicament, such as in an anticavity
treatment, as described herein. Suitable medicaments include oral
care compositions, toothpaste compositions, mouth rinse
compositions, floss coatings, chewing gums, and/or other suitable
compositions to be applied in the oral cavity.
[0149] Additionally, the oral care composition, as described
herein, can be used to reduce the number and/or intensity of white
spots on teeth, which can be attributable to caries presence with
the oral cavity.
[0150] The methods described above can be useful for any oral care
composition comprising hops, as described herein. The oral care
composition comprising hops can also include other ingredients
described above, such as metal, tin, zinc, fluoride, calcium,
biofilm modifier, polyphosphate, abrasive, humectant, flavor,
sweetener, prenylated flavonoid, thickening agent, buffering agent,
and/or water. Additionally, the oral care compositions useful in
the disclosed methods can be substantially free of, essentially
free of, or free of fluoride.
COMBINATIONS
[0151] A. Hops beta acid for use as medicament, preferably wherein
the medicament is an oral care composition, more preferred is a
toothpaste, a mouth rinse, a floss coating, or combinations
thereof. [0152] B. Hops beta acid as disclosed in A, wherein the
hops beta acid comprises less than about 1%, by weight of the hops
beta acid, of hops alpha acid, preferably wherein the hops beta
acid is essentially free of, substantially free of, or more
preferred free of hops alpha acid. [0153] C. Hops beta acid as
disclosed in A or B, wherein the medicament comprises metal,
preferably wherein the metal comprises tin, zinc, calcium, or
combinations thereof, more preferably wherein the tin comprises
stannous fluoride, stannous chloride, or combinations thereof.
[0154] D. Hops beta acid as disclosed in any of A to C, wherein the
medicament comprises abrasive, preferably wherein the abrasive
comprises silica abrasive, calcium abrasive, or combinations
thereof, more preferably wherein the calcium abrasive comprise
calcium carbonate, calcium pyrophosphate, calcium phosphate, or
combinations thereof. [0155] E. Hops beta acid as disclosed in any
of A to D, wherein the medicament is substantially free of,
essentially free of, or preferably free of fluoride. [0156] F. Hops
beta acid as disclosed in any of A to E, for use in prevention,
reduction and treatment of gingivitis, white spots in an oral
cavity, oral cavities, caries, or a combination thereof, preferably
wherein the white spots in the oral cavity are on teeth and
attributable to caries, cavities, and/or combinations thereof.
[0157] G. Hops for use in prevention, reduction and treatment of
gingivitis, white spots in an oral cavity, oral cavities, caries,
or a combination thereof, preferably wherein the white spots in the
oral cavity are on teeth and attributable to caries, cavities,
and/or combinations thereof. [0158] H. Hops as disclosed in G,
wherein the hops comprises hops extract, preferably wherein the
hops extract comprises hops beta acid, hops alpha acid, or
combinations thereof, more preferably wherein the hops beta acid
comprises less than about 1%, by weight of the extract, of hops
alpha acid, more preferred wherein the hops is essentially free of,
substantially free of, or free of hops alpha acid. [0159] I. Hops
as disclosed in G or H, wherein the hops is provided in an oral
care composition, preferably wherein the oral care composition is a
toothpaste, mouth rinse, floss coating, or combinations thereof.
[0160] J. Hops as disclosed in I, wherein the oral care composition
further comprises an abrasive, preferably wherein the abrasive
comprises silica abrasive, calcium abrasive, or combinations
thereof, more preferably wherein the calcium abrasive comprise
calcium carbonate, calcium pyrophosphate, calcium phosphate, or
combinations thereof. [0161] K. Hops as disclosed in I or J,
wherein the oral care composition further comprises a metal,
preferably wherein the metal comprises tin, zinc, calcium, or
combinations thereof, more preferably wherein the tin comprises
stannous fluoride, stannous chloride, or combinations thereof.
[0162] L. Hops as disclosed in any of I to K, wherein the oral care
composition is substantially free of, essentially free of, or
preferably free of fluoride. [0163] M. Hops as disclosed in any of
Ito L; wherein: the user is instructed to use the oral care
composition, preferably a toothpaste; wherein the instruction to
use comprise: [0164] (a) Dispensing the oral care composition,
preferably the toothpaste onto a toothbrush; [0165] (b) Applying
the oral care composition, preferably the toothpaste, to the oral
cavity for at least 1 minute; and [0166] (c) Expectorating the oral
care composition, preferably the toothpaste, from the oral cavity.
[0167] N. Hops as disclosed in M; wherein the instruction further
comprises to not swallow the oral composition.
EXAMPLES
[0168] The invention is further illustrated by the following
examples, which are not to be construed in any way as imposing
limitations to the scope of this invention. Various other aspects,
modifications, and equivalents thereof which, after reading the
description herein, may suggest themselves to one of ordinary skill
in the art without departing from the spirit of the present
invention or the scope of the appended claims.
Toothpaste Composition Instruction Example 1
[0169] The oral care compositions described herein can include the
following instructions:
[0170] Adults and children 12 years of age and older: Brush teeth
thoroughly, preferably after each meal or at least twice a day, or
as directed by a dentist or physician.
[0171] Children under 12 years of age: ask a dentist
[0172] This instruction is placed on the carton containing the
toothpaste composition including hops and/or on the toothpaste tube
comprising the toothpaste composition including hops. The
instruction can also include "Do not swallow."
[0173] Thus, in total, a user would perform these steps while a
manufacturer, distributor, and/or producer of the toothpaste
composition would instruct a user to perform these steps by placing
the instructions on the carton, tube, and/or combinations
thereof.
Toothpaste Composition Instruction Example 2
[0174] The oral care compositions described herein can include the
following instructions:
[0175] Adults and children 12 years of age and older: [0176] Apply
at least a 1-inch strip of the product onto a soft bristle
toothbrush [0177] Brush teeth thoroughly for at least 1 minute
twice a day (morning and evening), and not more than 3 times a day
or as recommended by a dentist or doctor. Make sure to brush all
areas of the teeth. Minimize swallowing. Spit out after
brushing.
[0178] Children under 12 years of age: consult a dentist or
doctor.
[0179] This instruction is placed on the carton containing the
toothpaste composition including hops and/or on the toothpaste tube
comprising the toothpaste composition including hops.
[0180] Thus, in total, a user would perform these steps while a
manufacturer, distributor, and/or producer of the toothpaste
composition would instruct a user to perform these steps by placing
the instructions on the carton, tube, and/or combinations
thereof.
Toothpaste Composition Instruction Example 3
[0181] The oral care compositions described herein can include the
following instructions:
[0182] Adults and children 2 years of age and older: [0183] Brush
teeth thoroughly, preferably after each meal or at least twice a
day, or as directed by a dentist or physician.
[0184] Children 2 to 6 years: [0185] Use only a pea sized amount
and supervise child's brushing and rinsing (to minimize
swallowing)
[0186] Children under 2 years: [0187] Ask a dentist or
physician
[0188] This instruction is placed on the carton containing the
toothpaste composition including hops and/or on the toothpaste tube
comprising the toothpaste composition including hops. The
instruction can also include "Do not swallow."
[0189] Thus, in total, a user would perform these steps while a
manufacturer, distributor, and/or producer of the toothpaste
composition would instruct a user to perform these steps by placing
the instructions on the carton, tube, and/or combinations
thereof.
Toothpaste Composition Instruction Example 4
[0190] The oral care compositions described herein can include the
following instructions:
[0191] Adults and children 2 years of age and older: [0192] Brush
teeth thoroughly after each meal or at least twice a day or use as
directed by a dentist [0193] To minimize swallowing use a pea-sized
amount in children under 6 [0194] Supervise children's brushing
until good habits are established [0195] Use only a pea sized
amount and supervise child's brushing and rinsing
[0196] Children under 2 years: [0197] Ask a dentist or
physician
[0198] This instruction is placed on the carton containing the
toothpaste composition including hops and/or on the toothpaste tube
comprising the toothpaste composition including hops. The
instruction can also include "Do not swallow."
[0199] Thus, in total, a user would perform these steps while a
manufacturer, distributor, and/or producer of the toothpaste
composition would instruct a user to perform these steps by placing
the instructions on the carton, tube, and/or combinations
thereof.
Toothpaste Composition Instruction Example 5
[0200] The oral care compositions described herein can include the
following instructions:
[0201] Adults and children 12 years of age and older: [0202] Apply
at least a 1-inch strip of the product onto a soft-bristled
toothbrush. Brush teeth thoroughly for at least 1 minute twice a
day (morning and evening) or as recommended by a dentist. [0203]
Children under 12 years old: ask a dentist
[0204] This instruction is placed on the carton containing the
toothpaste composition including hops and/or on the toothpaste tube
comprising the toothpaste composition including hops. The
instruction can also include "Do not swallow."
[0205] Thus, in total, a user would perform these steps while a
manufacturer, distributor, and/or producer of the toothpaste
composition would instruct a user to perform these steps by placing
the instructions on the carton, tube, and/or combinations
thereof.
Mouth Rinse Composition Instruction Example 1
[0206] The oral care compositions described herein can include the
following instructions:
[0207] Adults and children 12 years of age and older: [0208] Use
twice daily after brushing your teeth with a toothpaste [0209]
Vigorously swish 10 mL (2 teaspoonfuls) of rinse between your teeth
for 1 minute and then spit out. [0210] Do not eat or drink for 30
minutes after rinsing. [0211] Supervise children as necessary until
capable of using without supervision.
[0212] This instruction is placed on the carton containing the
mouth rinse composition including hops and/or on the mouth rinse
bottle comprising the mouth rinse composition including hops. The
instruction can also include "Do not swallow."
[0213] Thus, in total, a user would perform these steps while a
manufacturer, distributor, and/or producer of the mouth rinse
composition would instruct a user to perform these steps by placing
the instructions on the carton, bottle, and/or combinations
thereof.
Mouth Rinse Composition Instruction Example 2
[0214] The oral care compositions described herein can include the
following instructions:
[0215] Adults and children 6 years of age and older: Use twice a
day after brushing your teeth with a toothpaste. Vigorously swish
1.0 ml (2 teaspoonfuls) of rinse between your teeth for 1 minute
and then spit out. Do not eat or drink for 30 minutes after
rinsing. Instruct children under 12 years of age in good rinsing
habits (to minimize swallowing). Supervise children as necessary
until capable of using without supervision.
[0216] Children under 6 years of age: Consult a dentist or
doctor.
[0217] This instruction is placed on the carton containing the
mouth rinse composition including hops and/or on the mouth rinse
bottle comprising the mouth rinse composition including hops. The
instruction can also include "Do not swallow."
[0218] Thus, in total, a user would perform these steps while a
manufacturer, distributor, and/or producer of the mouth rinse
composition would instruct a user to perform these steps by placing
the instructions on the carton, bottle, and/or combinations
thereof.
Mouth Rinse Composition Instruction Example 3
[0219] The oral care compositions described herein can include the
following instructions:
[0220] Use after your normal brushing and flossing routine; rinse
toothpaste from mouth prior to use. Adults and children 6 yrs.
& older: Rinse for 30 seconds with 20 mL (4 teaspoonfuls) twice
a day. Children 6 years to under 12 years of age: supervise use.
Children under 6 years of age: do not use.
[0221] This instruction is placed on the carton containing the
mouth rinse composition including hops and/or on the mouth rinse
bottle comprising the mouth rinse composition including hops. The
instruction can also include "Do not swallow."
[0222] Thus, in total, a user would perform these steps while a
manufacturer, distributor, and/or producer of the mouth rinse
composition would instruct a user to perform these steps by placing
the instructions on the carton, bottle, and/or combinations
thereof.
Experimental Methods
Acid Production and Acid Inhibition [%]
[0223] Acid production and acid inhibition were determined with the
in vitro plaque glycolysis model (iPGRM). The purpose of this
technique is to provide a simple and quick method for determining
if compounds have an influence on the metabolic pathways that
plaque microorganisms utilize to produce toxins that adversely
affect gingival health.
[0224] The in vitro plaque glycolysis model (iPGRM) is a technique
in which plaque is grown from human saliva and treated with various
agents to determine anti-glycolytic activity of treatments. When
bacteria convert sugar into energy with the help of enzymes, acids
are formed. These acids demineralize and damage the dental enamel.
The purpose of this technique is to provide a simple and quick
method for determining if treatment compounds have an inhibitory
effect on the metabolic pathways that plaque microorganisms utilize
for the production of acids or toxins and/or inhibit their growth.
For the purposes of the work here, if the test therapeutic
compositions contain Sn, the Sn placebo should be tested.
Additionally, the antibacterial composition should be tested with
respect to its placebo to determine the iPGRM value for the
antibacterial composition only. This is important if buffers, e.g.,
bicarbonate, orthophosphate, calcium carbonate, are present in the
composition in addition to the antibacterial composition.
[0225] A plaque biofilm was grown on glass rods from fresh pooled
human saliva and Trypticase Soy Broth (TSB) at 37.degree. C. over 2
days by dipping glass rods into and out of media in a reciprocating
motion. Treatments were 2 minutes of dentifrice slurry in water
(1:5) or diluted treatment in water (1:5). After treatments,
biofilms were incubated with TSB and sucrose until pH indicator
showed a color change (.about.6 hrs). The pH of the media solutions
was then measured to determine the amount of glycolysis inhibition
relative to a negative control.
[0226] On Day 1, new glass rods (5 mm.times.90 mm) were polished
approximately 25 mm from the un-tapered end on a lathe with silicon
carbide paper of 240, 320, 400, and 600 grit used sequentially.
After the initial polishing, the rods should be polished with 600
grit paper before each test. After polishing, rods were stored
until ready to run test. Enough rods should be polished for a full
rack of treatments. A rack can treat 12 compositions with 4
replicates of each composition such that the rack has 48 rods.
[0227] On Day 2, saliva was collected daily during the test from a
panel of 5-10 people by paraffin stimulation and was refrigerated
at 4.degree. C. until it was needed throughout the day. Pool saliva
carefully (do not pour in wax/mucus) and mix thoroughly before use.
The rods were removed from storage, rinsed with deionized water to
remove any sanding residue, disinfected in 70% ethanol/water
solution, and were allowed to dry on a sterile surface.
Subsequently, the rods were loaded into a hanging rack of holders
that were used to dip the rods continuously into media vials
containing growth media. The rod heights were adjusted and each rod
was secured in place using a rubber o-ring. In the early afternoon,
7 mL of growth media (160 g of a solution of 3% TSB with 3% sucrose
was mixed with 240 g pooled human saliva. This TSB/sucrose solution
should be sterilized by autoclave before combining with the pooled
human saliva.) into media vials. The media vials were arranged
under the hanging rods on a rack in an incubation oven. The
incubator has been previously modified such that a dipping motor
can dip the rods into the media vials submerging 1.5 cm of the rod
into the growth media at a frequency of 1 dip per minute without
the rods touching the walls of the media vial. The rods were dipped
overnight this way.
[0228] On Day 3, an enriched growth media was prepared (500 g of a
solution of 3% TSB and 10% sucrose was mixed with 33 g pooled human
saliva. This TSB/sucrose solution should be sterilized by autoclave
before combining with the pooled human saliva.). This enriched
growth media was pipetted into a new set of media vials (7 mL per
vial) and was swapped for the overnight growth media from Day 1.
The rods were dipped throughout the day in this enriched growth
media for 5 hours at 37.degree. C. in the incubation oven. At the
end of the day, a new overnight growth media was prepared (40 g of
a solution of 3% TSB was mixed with 360 g pooled human saliva and
0.5 g sucrose), pipetted into a new set of media vials, and swapped
for the enriched growth media. The rods were dipped overnight in
the same fashion as on the first day.
[0229] On Day 4, a glycolysis media was prepared by combining 0.15
g TSB, 25 g sucrose, and 500 mL deionized water resulting in a
solution of 0.03% TSB and 0.5% sucrose in water. This solution was
mixed then sterilized in an autoclave. The pH was then adjusted to
6.5 using 0.1 M HCl and pipetted into new media vials (7 mL). Two
extra vials were filled than were needed for the rack of rods as pH
blanks. Two drops of chlorophenol red solution were added to each
of the 4 tubes that contained the negative control (Crest Cavity
Protection slurry). Three drops of bromocresol purple solution were
added to 2 tubes that contained the positive control (1%
Chlorhexidine solution). Set the rack aside until treatments are
complete. Vials were prepared containing 12 mL of deionized water
to rinse off the treatments. Vials were prepared containing the
treatment slurries/solutions (7 mL) of homogenized treatment and
water. The rods were dipped into the treatment vials for 2 minutes,
rinsed for 10 dips in a first set rinse vials, rinsed for 10 dips
in a second set of rinse vials, rinsed for 10 dips in a third set
of rinse vials, and returned to the incubator rack. The entire
biofilm was treated and rinsed. Once all treatments were complete,
the biofilms on the rods were fully submerged in the glycolysis
media inside the incubation oven with no dipping for 2 hours. After
two hours, the dipping apparatus was activated. The total
incubation time was between 3 to 7 hours. Incubation is terminated
when the pH value in the glycolysis media of the negative controls
is between 4.8-5.6, more ideally 4.9-5.2, and when the pH value in
the glycolysis media of the positive controls is above the negative
control. If the indicator dye in the positive control turns yellow,
i.e., the pH has dropped beneath 5.2, the incubation has gone on
too long and the test will need to be repeated.
[0230] After incubation termination on Day 4, the rods were removed
from the glycolysis media and allowed to dry in the oven. The
glycolysis media was removed from the incubation oven, allowed to
return to room temperature, and the pH was measured in each vial
and the blank vials to determine the average pH change of the media
following treatment. The change in pH is determined with respect to
the blank vials. If the final pH of the blank is less than 6.6, the
test needs to be repeated. If the difference between the positive
and negative control is not significant in a student's t-test, the
test needs to be repeated. If the change in pH of the negative
control with respect to the blank is less than 1, the test needs to
be repeated.
[0231] After the pH values of all the vials were measured, the
.DELTA.pH per vial was determined by subtracting its pH from the
average pH of the blanks. The glycolysis inhibition efficacy is
determined from the following formula. The average .DELTA.pH of a
treatment was determined by averaging the results from the four
replicate vials per treatment.
Acid Inhibition ( % ) = 1 0 0 - ( Avg .DELTA. pH sample Avg .DELTA.
pH neg ctrl ) .times. 1 0 0 Formula 2 ##EQU00001##
[0232] If the efficacy of the positive control (1% Chlorhexidine
solution) is not between about 65% to about 85% with respect to the
negative control (Crest Cavity Protection, Procter & Gamble,
Cincinnati, Ohio), the test was repeated.
Anticaries Activity
[0233] The test design used here is similar to those found in the
FDA Method #37 of the Fluoride Anti-Caries OTC Monograph. The major
variations are the diet used (MIT 200 rather than #469), the caries
score method (Keyes method rather than HMA), and treatment
frequency. Experimental procedures were conducted according to the
FDA regulations Part 58.
[0234] Using litters as a covariate, the use of between 50 and 58
(depending on the type of fluoride) animals per treatment group
satisfies the most stringent power requirements of the ADA's
Council on Dental Therapeutics 20% clinical difference between
treatments at 80% power. However, we have been routinely using 40
animals per treatment group and both the ADA's CDT and the FDA have
consistently accepted these tests. This requires initiating the
study with 40 animals per group. Twenty-three (23) litters provided
these animals. When studies are sized as such, treatment
differences of approximately 16% have been found to be significant
on occasion, thus is generally considered the cusp of clinical
significance.
[0235] All protocols are reviewed and approved by the Institutional
Animal Care and Use Committee prior to the receipt of animals.
[0236] The animals were weanling mixed-sex Sprague Dawley rats;
weighing 29-53 grams. Due to the shipping schedule of the supplier,
the dams were received with their entire birth litter. The litters
were received when the pups were 6 days of age and litter size was
reduced at 8 days of age to ten (10) pups per litter. Twenty-five
(25) litters were purchased. The five extra litters were to allow
for any mortality prior to stratification. Any unused animals were
euthanized after the study stratification.
[0237] The litters were maintained in large solid-bottom (box-type)
cages with dams until the pups were weaned at 18 days of age.
Starting at 9 days of pup age, the dams were rotated daily among
the litters until the pups were weaned at 18 days of age. The pups
were maintained in the box cages until 21 days of age. At that
time, the pups were stratified and housed in pairs in suspended
wire-bottomed cages that had been cleaned and sanitized prior to
usage. The change in caging was required to prevent artificially
increasing the caries rate due to direct contact bedding. The cages
were arranged so that all animals of the individual groups were
together and the cages were labeled with group designation and
treatment (treatment code) that the animals received.
[0238] When the pups were 21 days of age they were given unique
numbers by ear-punch with records kept of littermates. Animals were
assigned to groups in such a manner that groups were balanced for
litter, weight and sex. There were 40 animals per group.
[0239] Upon receipt, dams and litters were provided rodent lab diet
until the pups were 8 days of age. On day 8 (pup age) dams and
litters were provided Diet MIT 305. Pups were provided Diet MIT 200
ad libitum at day 18 (pup age) and throughout the test period. All
animals were provided with deionized water ad libitum.
[0240] Box caging was changed at day 13 and again at day 18 of pup
age. Following administration of the inoculum, box cages and the
bedding were decontaminated by autoclaving prior to sanitizing.
Cage boards were changed three times a week at the time when fresh
food and water were given (Monday, Wednesday and Friday). Clean and
sanitized water bottles and food jars were provided weekly.
Suspended caging and banks were sanitized bi-weekly. The animals
were observed daily by a staff member and weekly by the attending
veterinarian for any signs of health problems. The animals were
housed in an AAALAC-accredited facility. Room temperature was
maintained at 72.degree. F. (.+-.6.degree. F.) with 10-15 air
changes per hour and a 12-hour light cycle.
[0241] On day 15 (pup age), the animals received an oral
inoculation of streptomycin-resistant S. sobrinus 6715 (ATCC strain
#27352) culture. This involved flooding the mouth with 0.2 ml of
culture/animal. On day 18 (pup age) the animals were inoculated
with S. sobrinus for three consecutive days (age 18, 19 and 20
days). This involved placing 0.1 ml of the S. sobrinus culture on
the occlusal surfaces of each of the mandibular molar quadrants,
putting 10 cc of this concentration-adjusted culture into each
sanitized and filled water bottle, and lightly spraying the bedding
with no more than 10 cc of the remaining culture. All water bottles
were removed and sanitized 24 hours after inoculum has been added.
The inoculums were administered to the animals with a 200
micropipette.
[0242] The treatment phase began at day 22 of pup age. Each
treatment had a labeled plastic beaker that was designated for that
treatment only. Fresh materials (i.e., obtained from the stock
supply) were used for each treatment. The dentifrices were mixed in
a 1:1 ratio (by weight) with deionized water. Specifically, 10
grams of dentifrice was weighed into a 30 ml beaker; 10 grams of
deionized water was then added to the dentifrice. The mixture was
then stirred by hand (30 seconds) with a clean micro spatula for
the purpose of creating a smooth mixture. The beaker containing the
slurry and a small magnetic stirring bar was placed on a magnetic
stirrer, which was set at the lowest speed and allowed to stir for
four (4) minutes prior to treatm4ent. The slurry was prepared
immediately prior to each treatment.
[0243] A cotton-tipped applicator was dipped into the slurry (for 2
seconds) and was applied to one-half of the rat's mouth in such a
way that the sides of the applicator came into contact with both
the mandibular and maxillary molars on one side of the mouth. The
treatment was accomplished by using a rolling motion of the sides
of the applicator over the mandibular and maxillary molar teeth for
15 seconds. The applicator was dipped into the slurry for the
second time (again, for 2 seconds) and the other side of the rat's
mouth similarly treated for 15 seconds. A new applicator was used
for each animal.
[0244] Treatments were administered twice daily for five days with
a single daily treatment on weekends. The first treatment each day
began at approximately the same time every day, and the second
treatment did begin no earlier than six hours after the first
treatment. Singular treatments were given at a 24-hour interval on
weekends. Treatment materials were stored at room temperature. All
treatment products were returned to sponsor at study
completion.
[0245] One week after the initiation of the inoculation regimen and
at study termination, an oral swabbing was taken from each rat
using a sterile cotton swab (six-inch, single-tipped applicator).
The microorganisms on the mandibular and maxillary molar teeth were
sampled, using a rolling motion of the swab for 15 seconds on one
side of the mouth, rolled over the tongue, and rolled over the
molar teeth on the other side of the mouth for an additional 15
seconds. Immediately after the applicator was removed from the
animal's mouth, it was streaked across half of a 100 mm petri plate
containing Mitis Salivarius agar to which 200 units/ml of
streptomycin sulfate was added. The plates were incubated for 48
hours at 37.degree. C. with 10% CO.sub.2. The colony count taken
after the 48 hours of incubation was recorded in the logbook.
[0246] The experimental duration of the rat caries studies was
three weeks. Immediately prior to termination, all animals were
observed for any visual signs of ill health or pathology,
individually weighed and an oral swabbing taken to confirm S.
sobrinus implantation. The animals were euthanized by carbon
dioxide inhalation. Code numbers were assigned to each animal and
the heads were then removed, placed in individual jars along with
the code number, and cooked under pressure (10 PSI for 12 minutes).
The hemijaws were then removed and freed of all soft tissue.
[0247] The cleaned hemijaws (four quadrants) were put into plastic
vials with the code numbers taped to the vial. A murexide solution
(0.3 g murexide; 300 ml DI H2O and 700 ml of ethanol) was added to
each vial and the jaws were allowed to stain overnight. The jaws
were then rinsed and allowed to air dry.
[0248] The hemijaws were microscopically examined for smooth
surface caries, sectioned, and then microscopically examined for
sulcal and interproximal caries using the Keyes Method. The scoring
method is detailed in Navia, J N, Animal Models in Dental Research,
pp 287-290, 1977; and Keyes, PH, J. Dent. Res. 37:1088-1099, 1958.
All analyses were performed using SAS statistical software, version
9.4. The groups were compared using analysis of variance (ANOVA),
with a fixed effect for group and a random effect for litter. The
litter effect was included in the models to reduce a known factor
affecting the variability of the measurements. Pair-wise
comparisons between groups were made using Tukey's multiple
comparisons procedure to control the overall significance level
(.alpha.=0.05) of the comparisons.
[0249] The specific types of data, which were tabulated, and
statistically analyzed may include:
[0250] 1) Mortality Data Experimental Phase [0251] a. Initial
number of animals [0252] b. Final number of animals [0253] c.
Percent mortality
[0254] 2) Growth Data Experimental Phase [0255] a. Initial body
weight (mean.+-.S.E.M.)
[0256] b. Final body weight (mean.+-.S.E.M.)
[0257] 3) Caries Experience [0258] a. Enamel and dentinal
involvement of smooth surface (buccal, lingual) lesions
(mean.+-.S.E.M.) [0259] b. Enamel and dentinal involvement of
interproximal lesions (mean.+-.S.E.M.) [0260] c. Enamel and
dentinal involvement of total smooth surface (buccal, lingual &
interproximal) lesions (mean.+-.S.E.M.) [0261] d. Enamel and
dentinal involvement of sulcal lesions (mean.+-.S.E.M.) [0262] e.
Total caries involvement combining the scores from the Keyes method
of scoring smooth surface, interproximal, and sulcal caries
(mean.+-.S.E.M.)
Preparation of Oral Care Compositions
[0263] The oral care compositions of TABLE 1A were prepared by
combining one or more humectants, water, sweetener(s), tin ion
source, sodium gluconate, and/or flavor(s) to create a liquid
mixture. The liquid mixture was homogenized at 25.degree. C. for 2
minutes. Next, sodium hydroxide (50% solution) was added to the
liquid mixture and the liquid mixture was homogenized at 25.degree.
C. for 2 minutes. A separate powder mixture was prepared by
combining a portion of the calcium ion source and any thickening
agents, such as xanthan gum and/or sodium carboxymethylcellulose.
The powder mixture was then combined with the liquid mixture. Next,
the surfactant, such as sodium lauryl sulfate, was added to the
mixture. The contents were homogenized at 25.degree. C. for 2
minutes. The hops extract was then combined with the mixture and
homogenized at 25.degree. C. for 2 minutes. Finally, the remaining
portion of the calcium ion source and the buffering agent were
combined with the mixture and homogenized at 25.degree. C. for 2
minutes.
TABLE-US-00001 TABLE 1A Oral Care Compositions Formula A Formula B
Formula C Glycerin 49.10 47.80 -- Sorbitol -- -- 37.98 Water -- --
13.00 Sodium Monofluorophosphate -- 1.15 -- Sodium Gluconate 1.00
1.00 1.00 SnCl.sub.2 1.10 1.10 1.10 CaCO.sub.3 32.00 32.00 32.00
Xanthan Gum 0.50 0.50 0.30 Carboxymethylcellulose -- -- 1.00
Carbomer 1.00 1.00 -- Sodium Lauryl Sulfate 1.40 1.40 1.29 Flavor
1.00 1.00 1.00 Sodium Saccharin 0.40 0.40 0.50 Stevia Glycosides
0.30 0.30 -- Sodium Hydroxide 1.20 1.35 0.33 Hops Beta Acid
Extract* 0.50 0.50 0.50 Sodium Bicarbonate 10.00 10.00 10.00
Titanium Dioxide 0.50 0.50 -- *Hops Beta Acid Extract supplied by
Hopsteiner .RTM., with 45% hops beta acids and less than 1% hops
alpha acids
[0264] Formula A, B, and C, as shown in TABLE 1A, were prepared in
accordance with the Experimental Methods, described above. The Hops
Beta Acids were supplied by Hopsteiner.RTM. as an extract from
Humulus lupulus. The Hopsteiner.RTM. extract was approximately 45%,
by weight of the extract, of hops beta acids and less than 1%, by
weight of the extract, of hops alpha acids. Formula A and B have
hops beta acids with no independently added water. Formula A and B
differ only in that Formula B includes a fluoride ion source
(sodium monofluorophosphate, NaMFP), which was used in the total
enamel caries test shown in TABLE 4. Formula C include hops beta
acids without fluoride in a high-water chassis.
TABLE-US-00002 TABLE 1B Hops Beta Acids Extract Specification
Ingredient Amount (wt %) Hops Beta Acids 45 .+-. 2 Hops Alpha Acids
0.4 .+-. 0.3 Hops oils 1.5 .+-. 0.5 Propylene Glycol 20 .+-. 15
Water <8% pH 11 .+-. 0.5
[0265] TABLE 1B describes the hops beta acid extract provided by
Hopsteiner.RTM.. Since the hops beta acids are provided as an
extract, there can be some variability in the amounts of certain
ingredients. However, the extract comprises approximately 45%, by
weight of the extract, of the hops beta acids and approximately
0.4%, by weight of the extract, of hops alpha acids. This is
dramatically different to previous hops extracts which typically
have more hops alpha acids than hops beta acids. Other minor
ingredients may be present in the Hops Beta Acid extract.
TABLE-US-00003 TABLE 2 Acid Production and Glycolysis Inhibition
[%] after treatment of 3-day biofilm Acid Production Mean Acid
(.DELTA.pH) Inhibition (%) Treatment Mean SE Mean SE Crest .RTM.
Cavity Protection (NaF) 1.55 0.027 3.43 1.68 Crest .RTM. Pro-Health
.TM. Advanced (SnF.sub.2) 0.91 0.038 43.14 2.39 Crest .RTM. Gum
Care (SnF.sub.2 + SnCl.sub.2) 0.51 0.025 68.49 1.55 1%
Chlorhexidine 0.4 0.018 75.12 1.11 Formula A (Hops Beta Acids +
SnCl.sub.2) -0.05 0.022 102.96 1.34 Formula C (Hops Beta Acids +
SnCl.sub.2) 0 0.013 100.08 0.79
[0266] TABLE 2 displays the change in acid production in a 3-day
biofilm using the iPGRM test described herein. After treatment with
a commercial Crest.RTM. toothpaste containing sodium fluoride, the
acid product mean is 1.55 with a mean inhibition of 3.43%.
Treatment of the 3-day biofilm with a Crest.RTM. toothpaste
containing stannous fluoride resulted in decreases in acid
production and a net mean acid inhibition of 43.14% (Crest.RTM.
Pro-Health.TM.) and 68.49% (Crest.RTM. Gum Care). This was an
expected result as the stannous ion is known to act as an
antibacterial, which can lower the number of bacteria producing
acid in the biofilm. Crest.RTM. Gum Care performed slightly better
than Crest.RTM. Pro-Health.TM. 0due to additional amounts of
stannous ions (i.e. SnCl.sub.2). Chlorhexidine is an antibacterial
agent that can be prescribed to treat gingivitis. Treatment with
chlorhexidine resulted in a mean acid inhibition of 75.12%, which
was not unexpected because chlorhexidine is known as an extremely
effective antibacterial agent.
[0267] TABLE 2 also shows that Formula A and C displayed
essentially zero acid production with a mean acid inhibition of
approximately 100%. It was unexpected that Formula A and C (without
a fluoride ion source) would be essentially 100% effective at
preventing acid production without having fluoride and/or
chlorhexidine, two of the most prevalent and effective
antibacterial agents.
TABLE-US-00004 TABLE 3 Total Enamel Caries Total Enamel % Positive
% Negative Treatment Caries Control Control Silica Placebo.sup.a
38.70 .+-. 2.06 47 0 Silica + NaMFP.sup.b 31.55 .+-. 2.08 75 19
Crest .RTM. Cavity 25.28 .+-. 1.99 100 35 Protection.sup.c Formula
A 26.23 .+-. 2.01 96 32 .sup.aSilica placebo is the negative
control without any fluoride ion source .sup.bNaMFP at 1000 ppm
.sup.cNaF 1100 ppm + Silica is the positive control with silica and
a fluoride ion source
[0268] TABLE 3 displays the results from the rat caries test, FDA
No. 37. The rat caries test a biological test method required by
the U.S. FDA monograph to show efficacy of an anticaries drug,
currently including only fluoride ion sources. As shown in TABLE 3,
the negative control, Silica Placebo, is a toothpaste with silica
abrasive, but not any fluoride ion source. Silica+NaMFP is a USP
NaMFP toothpaste with sodium monofluorophosphate and a silica
abrasive. Crest.RTM. Cavity Protection is a toothpaste with sodium
fluoride and a silica abrasive. In contrast, Formula A has no
fluoride ion source or silica abrasive, but has hops beta acids and
stannous chloride. Unexpectedly, Formula A (26.23), without any
fluoride ion source, performed similar to the Crest.RTM. Cavity
Protection (25.28), a dentifrice with 1100 ppm sodium fluoride.
Additionally, Formula A performed better than a dentifrice with
sodium monofluorophosphate with silica abrasive (26.23 for Formula
A vs. 31.55 for NaMFP). The only anticaries drugs listed in the
U.S. FDA monograph are stannous fluoride, sodium fluoride, and
sodium monofluorophosphate. In other words, Formula A is a
fluoride-free anticavity toothpaste.
[0269] The dimensions and values disclosed herein are not to be
understood as being strictly limited to the exact numerical values
recited. Instead, unless otherwise specified, each such dimension
is intended to mean both the recited value and a functionally
equivalent range surrounding that value. For example, a dimension
disclosed as "40 mm" is intended to mean "about 40 mm."
[0270] Every document cited herein, including any cross referenced
or related patent or application and any patent application or
patent to which this application claims priority or benefit
thereof, is hereby incorporated herein by reference in its entirety
unless expressly excluded or otherwise limited. The citation of any
document is not an admission that it is prior art with respect to
any invention disclosed or claimed herein or that it alone, or in
any combination with any other reference or references, teaches,
suggests or discloses any such invention. Further, to the extent
that any meaning or definition of a term in this document conflicts
with any meaning or definition of the same term in a document
incorporated by reference, the meaning or definition assigned to
that term in this document shall govern.
[0271] While particular embodiments of the present invention have
been illustrated and described, it would be obvious to those
skilled in the art that various other changes and modifications can
be made without departing from the spirit and scope of the
invention. It is therefore intended to cover in the appended claims
all such changes and modifications that are within the scope of
this invention.
* * * * *