U.S. patent application number 17/694044 was filed with the patent office on 2022-06-23 for oral care compositions and methods of using the compositions.
This patent application is currently assigned to Colgate-Palmolive Company. The applicant listed for this patent is Colgate-Palmolive Company. Invention is credited to Mary COLLIGAN, Nihal DOGU, Steven FISHER, Andre MORGAN, Aarti REGE, Richard SULLIVAN, David SURIANO.
Application Number | 20220192944 17/694044 |
Document ID | / |
Family ID | 1000006196611 |
Filed Date | 2022-06-23 |
United States Patent
Application |
20220192944 |
Kind Code |
A1 |
REGE; Aarti ; et
al. |
June 23, 2022 |
Oral Care Compositions and Methods of Using the Compositions
Abstract
An oral care composition comprising zinc phosphate and stannous
fluoride.
Inventors: |
REGE; Aarti; (East Windsor,
NJ) ; SULLIVAN; Richard; (Atlantic Highlands, NJ)
; SURIANO; David; (Edison, NJ) ; DOGU; Nihal;
(Dayton, NJ) ; COLLIGAN; Mary; (Hillsborough,
NJ) ; FISHER; Steven; (Middlesex, NJ) ;
MORGAN; Andre; (Robbinsville, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Colgate-Palmolive Company |
New York |
NY |
US |
|
|
Assignee: |
Colgate-Palmolive Company
New York
NY
|
Family ID: |
1000006196611 |
Appl. No.: |
17/694044 |
Filed: |
March 14, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16291472 |
Mar 4, 2019 |
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17694044 |
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15630246 |
Jun 22, 2017 |
10258551 |
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16291472 |
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62354247 |
Jun 24, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/36 20130101; A61K
8/24 20130101; A61K 9/0056 20130101; A61K 8/21 20130101; A61K 8/27
20130101; A61K 2800/51 20130101; A61K 8/0204 20130101; A61Q 11/00
20130101 |
International
Class: |
A61K 8/27 20060101
A61K008/27; A61K 8/36 20060101 A61K008/36; A61K 8/02 20060101
A61K008/02; A61K 8/21 20060101 A61K008/21; A61K 8/24 20060101
A61K008/24; A61K 9/00 20060101 A61K009/00; A61Q 11/00 20060101
A61Q011/00 |
Claims
1-17. (canceled)
18. A method of treating or reducing bacterial colonization and
biofilm development in the oral cavity in a subject in need
thereof, wherein the method comprises administering an oral care
composition comprising: an orally acceptable carrier; zinc
phosphate; stannous fluoride; and wherein the oral care composition
is administered to the oral cavity of the subject in need
thereof.
19. The method of claim 18, wherein the zinc phosphate is a
preformed salt of zinc phosphate.
20. The method of claim 18, wherein zinc phosphate is present in an
amount sufficient so that the stannous fluoride dissociates to
provide a therapeutically effective amount of stannous ions in
aqueous solution.
21. The method of claim 18, wherein the amount of zinc phosphate is
from 0.05 to 5% by weight, relative to the weight of the oral care
composition.
22. The method of claim 18, wherein the amount of the stannous
fluoride is from 0.05% to 5% by weight, relative to the weight of
the oral care composition.
23. The method of claim 18, wherein the amount of the water is
about 12% by weight or more, relative to the weight of the oral
care composition.
24. The method of claim 18, wherein the oral care composition
further comprises an abrasive.
25. The method of claim 18, further comprising one or more
humectants and/or one or more surfactants.
26. The method of claim 18, further comprising an effective amount
of one or more alkali phosphate salts.
27. The method of claim 18, further comprising a whitening
agent.
28. The method of claim 18, further comprising one or more sources
of zinc ions in addition to the zinc phosphate.
29. The method of claim 18, wherein the oral care composition is a
dentifrice, powder, cream, strip or gum.
30. The method of claim 18, wherein the oral care composition
comprises: from 0.5 to 3% by weight zinc phosphate; from 0.05 to
11% by weight stannous fluoride; from 1 to 8% by weight alkali
phosphate salts selected from sodium phosphate dibasic, potassium
phosphate dibasic, dicalcium phosphate dihydrate, tetrasodium
pyrophosphate, tetrapotassium pyrophosphate, calcium pyrophosphate,
sodium tripolyphosphate, and mixtures of any two or more of these,
relative to the weight of the oral care composition; and a silica
abrasive.
31. The method of claim 18, wherein the oral care composition is a
gel.
32. The method of claim 18, wherein the pH of the oral care
composition is less than 7.
33. The method of claim 18, wherein the amount of zinc phosphate in
the oral care composition is from 0.9 to 1.1% by weight, relative
to the weight of the oral care composition, and wherein the amount
of stannous fluoride is from 0.4 to 0.5% by weight, relative to the
weight of the oral care composition.
Description
BACKGROUND
[0001] Dental erosion involves demineralization and damage to the
tooth structure due to acid attack from nonbacterial sources.
Erosion is found initially in the enamel and, if unchecked, may
proceed to the underlying dentin. Dental erosion may be caused or
exacerbated by acidic foods and drinks, exposure to chlorinated
swimming pool water, and regurgitation of gastric acids.
[0002] The tooth enamel is a negatively charged surface, which
naturally tends to attract positively charged ions such as hydrogen
and calcium ions, while resisting negatively charged ions such as
fluoride ions. Depending upon relative pH of surrounding saliva,
the tooth enamel will lose or gain positively charged ions such as
calcium ions. Generally saliva has a pH between 7.2 and 7.4. When
the pH is lowered the fluid medium surrounding the tooth becomes
undersaturated with respect to the tooth mineral phase and the
tooth dissolves, releasing calcium and phosphate ions. This damages
the enamel and creates a porous, sponge-like roughened surface. If
saliva remains acidic over an extended period, then
remineralization may not occur, and the tooth will continue to lose
minerals, causing the tooth to weaken and ultimately to lose
structure.
[0003] Heavy metal ions, such as zinc, are resistant to acid
attack. Zinc ranks above hydrogen in the electrochemical series, so
that metallic zinc in an acidic solution will react to liberate
hydrogen gas as the zinc passes into solution to form di-cations,
Zn.sup.2+. Zinc has also been shown to have anti-microbial
properties in plaque and caries studies.
[0004] Soluble zinc salts, such as zinc citrate, have been used in
dentifrice compositions, but have several disadvantages. Zinc ions
in solution impart an unpleasant, astringent mouthfeel, so
formulations that provide effective levels of zinc, and also have
acceptable organoleptic properties, have been difficult to achieve.
Moreover, free zinc ions may react with fluoride ions to produce
zinc fluoride, which is insoluble and so reduces the availability
of both the zinc and the fluoride. Finally, the zinc ions will
react with anionic surfactants such as sodium lauryl sulfate, thus
interfering with foaming and cleaning.
[0005] Zinc phosphate (Zn.sub.3(PO.sub.4).sub.2) is insoluble in
water, although soluble in acidic or basic solutions, e.g.,
solutions of mineral acids, acetic acid, ammonia, or alkali
hydroxides. See, e.g., Merck Index, 13.sup.th Ed. (2001) p. 1812,
monograph number 10205. Partly because it is viewed in the art as a
generally inert material, zinc phosphate is commonly used in dental
cements, for example in cementation of inlays, crowns, bridges, and
orthodontic appliances, which are intended to endure in the mouth
for many years. Zinc phosphate dental cements are generally
prepared by mixing zinc oxide and magnesium oxide powders with a
liquid consisting principally of phosphoric acid, water, and
buffers, so the cement comprising zinc phosphate is formed in situ
by reaction with phosphoric acid.
[0006] Stannous fluoride is well known for use in clinical
dentistry with a history of therapeutic benefits over forty years.
However, until recently, its popularity has been limited by its
instability in aqueous solutions. The instability of stannous
fluoride in water is primarily due to the reactivity of the
stannous ion (Sn.sup.2+). Tin readily hydrolyses above a pH of 4,
resulting in precipitation from solution, with a consequent loss of
the therapeutic properties.
[0007] Approaches to overcoming the stability problem with stannous
fluoride include forming a gel in no or very low water formulations
by dissolving stannous fluoride in an anhydrous material such as
glycerin, or by using a chelating agent. However, these can be
relatively expensive and tedious solutions.
[0008] There is a desire for improved compositions for treating and
reducing erosion of tooth enamel. There is also a desire for novel
anti-microbial compositions that are stable in water and relatively
simple to manufacture.
BRIEF SUMMARY
[0009] An embodiment of the present disclosure is directed to an
oral care composition comprising zinc phosphate and stannous
fluoride. In some embodiments, the zinc phosphate is added to the
dentifrice as a preformed salt.
[0010] Further areas of applicability of the present disclosure
will become apparent from the detailed description provided
hereinafter. It should be understood that the detailed description
and specific examples, while indicating the preferred embodiment of
the disclosure, are intended for purposes of illustration only and
are not intended to limit the scope of the disclosure.
DETAILED DESCRIPTION
[0011] The following description of the preferred embodiment(s) is
merely exemplary in nature and is in no way intended to limit the
disclosure, its application, or uses.
[0012] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
referenced in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls.
[0013] Unless otherwise specified, all percentages and amounts
expressed herein and elsewhere in the specification should be
understood to refer to percentages by weight. The amounts given are
based on the active weight of the material.
[0014] An embodiment of the present disclosure is directed to an
oral care composition for intermittent use, e.g., daily use, in the
form of a dentifrice, gel, lozenge, mint, chewing gum or other
suitable oral care formulation. The oral care composition comprises
zinc phosphate, stannous fluoride and water. In some embodiments,
the zinc phosphate is added to the oral care composition as a
preformed salt. As used herein, the term "preformed salt"--when
used in reference to zinc phosphate--means that the zinc phosphate
is not formed in situ in the oral care composition, e.g., through
the reaction of phosphoric acid and another zinc salt.
[0015] In one aspect, the present disclosure therefore provides an
oral care composition (Composition 1) comprising an orally
acceptable carrier, zinc phosphate and stannous fluoride. In
further embodiments of this aspect, the present disclosure
provides: [0016] 1.1 Composition 1, wherein the zinc phosphate is a
preformed salt of zinc phosphate. [0017] 1.2 Composition 1 or 1.2,
wherein the zinc phosphate is present in an amount sufficient so
that the stannous fluoride dissociates to provide a therapeutically
effective amount of stannous ions in aqueous solution. [0018] 1.3
Any preceding composition, wherein the amount of zinc phosphate is
from 0.05 to 5% by weight, relative to the weight of the oral care
composition, for example, from 0.1 to 4% by weight, or from 0.5 to
3% by weight, or from 0.5 to 2% by weight, or from 0.8 to 1.5% by
weight, or from 0.9 to 1.1% by weight, or about 1% by weight, or
from 2 to 3% by weight, or about 2%, or about 2.25% or about 2.5%,
by weight. [0019] 1.4 Any preceding composition, wherein the amount
of the stannous fluoride is from 0.05% to 11% by weight, relative
to the weight of the oral care composition, for example, from 0.05
to 7% by weight, or from 0.1% to 5% by weight, or from 0.2 to 3% by
weight, or from 0.2 to 2% by weight, or from 0.2 to 1% by weight,
or from 0.2 to 0.8% by weight, or from 0.4 to 0.6% by weight, or
from 0.4 to 0.5% by weight, or about 0.45% by weight (e.g.,
0.454%). [0020] 1.5 Any preceding composition, wherein the amount
of the water is about 12% by weight or more, relative to the weight
of the oral care composition, for example, from 15% to 85%, or from
20% to 75%, or from 20% to 40% or from 20% to 30%, or from 25% to
50%, or from 30% to 40%, for example, about 35%, or about 25% or
about 20%. [0021] 1.6 Any preceding composition, wherein the oral
care composition further comprises an abrasive, for example, silica
abrasives, calcium abrasives, and other abrasives as disclosed
herein. [0022] 1.7 Any preceding composition, further comprising
one or more humectants and/or one or more surfactants, as described
herein. [0023] 1.8 Any preceding composition, further comprising an
effective amount of one or more alkali phosphate salts for example
orthophosphates, pyrophosphates, tripolyphosphates, tetraphosphates
or higher polyphosphates. [0024] 1.9 Composition 1.8, wherein the
alkali phosphate salts comprise tetrasodium pyrophosphate or
tetrapotassium pyrophosphate, for example, in an amount of 0.5 to
5% by weight of the composition, e.g., 1-3%, or 1-2% or about 2% by
weight, or about 2-4%, or about 3-4% or about 4% by weight of the
composition. [0025] 1.10 Composition 1.8 or 1.9, wherein the alkali
phosphate salts comprise sodium tripolyphosphate or potassium
tripolyphosphate, for example, in an amount of 0.5 to 6% by weight
of the composition, e.g., 1-4%, or 2-3% or about 3% by weight.
[0026] 1.11 Any preceding composition, further comprising a
whitening agent. [0027] 1.12 Any preceding composition, further
comprising one or more sources of zinc ions in addition to the zinc
phosphate, for example a zinc salt selected from zinc citrate, zinc
oxide, zinc lactate, zinc pyrophosphate, zinc sulfate, or zinc
chloride. [0028] 1.13 Any preceding composition, wherein the oral
care composition is a dentifrice. [0029] 1.14 Any preceding
composition, wherein the composition comprises [0030] from 0.5 to
3% by weight zinc phosphate; [0031] from 0.05 to 11% by weight
stannous fluoride; [0032] from 1 to 8% by weight alkali phosphate
salts selected from sodium phosphate dibasic, potassium phosphate
dibasic, dicalcium phosphate dihydrate, tetrasodium pyrophosphate,
tetrapotassium pyrophosphate, calcium pyrophosphate, sodium
tripolyphosphate, and mixtures of any two or more of these,
relative to the weight of the oral care composition; and [0033] a
silica abrasive. [0034] 1.15 Any preceding composition, wherein the
composition is essentially free of a halogenated diphenyl ether.
[0035] 1.16 Any preceding composition, wherein the oral care
composition is a dentifrice (e.g., a toothpaste or oral gel),
powder (e.g., tooth powder), cream, strip or gum (e.g., chewing
gum), for example, wherein the oral care composition is a gel.
[0036] 1.17 Any preceding composition, wherein the oral care
composition is a lozenge or mint. [0037] 1.18 Any preceding
composition, wherein the oral care composition is a chewing gum.
[0038] 1.19 Any preceding composition, wherein the pH of the
composition is from 6 to 9, such as from 6.5 to 8, or from 3 to 7
or from 4 to 7 or from 5 to 7, or from 5 to 6. [0039] 1.20 Any
preceding composition, wherein the composition is a single-phase
composition (e.g., not a dual-phase composition). [0040] 1.21 Any
preceding composition, wherein the composition does not comprise
one or more of zinc oxide, zinc citrate, or zinc lactate. [0041]
1.22 Any preceding composition, wherein the zinc phosphate is the
only zinc ion source. [0042] 1.23 Any preceding composition,
wherein the composition is essentially free of hexametaphosphate
salts (e.g., sodium hexametaphosphate).
[0043] Any amount of zinc phosphate that is effective for
protecting against enamel erosion and/or providing any of the other
benefits described herein can be employed. Examples of suitable
amounts of zinc phosphate can range from 0.05 to 5% by weight, such
as from 0.1 to 4% by weight, or from 0.5 to 3% by weight, or from
0.5 to 2% by weight, or from 0.8 to 1.5% by weight, or from 0.9 to
1.1% by weight, or about 1% by weight, relative to the weight of
the oral care composition.
[0044] While zinc phosphate is considered insoluble (e.g., poorly
soluble), in water, when placed in formulation, e.g., at acidic or
basic pH, zinc phosphate can dissolve sufficiently upon use to
provide an effective concentration of zinc ions to the enamel,
thereby protecting against erosion, reducing bacterial colonization
and biofilm development, and providing enhanced shine to the teeth.
It has also been discovered that zinc phosphate in a formulation
with a second phosphate source enhances phosphate deposition. As
explained in WO2014/088573, the disclosure of which is hereby
incorporated by reference in its entirety, this is all unexpected,
in view of the poor solubility of zinc phosphate, and the
art-recognized view that it is substantially inert in conditions in
the oral cavity, as evidenced by its widespread use in dental
cement. At the same time, the formulations containing zinc
phosphate do not exhibit the poor taste and mouthfeel, poor
fluoride delivery, and poor foaming and cleaning associated with
conventional zinc-based oral care products, which use more soluble
zinc salts.
[0045] An amount of stannous fluoride, preferably an effective
amount, is employed in combination with the zinc phosphate in the
compositions of the present disclosure. For example, the stannous
fluoride can be employed in an amount that is effective for
providing anti-microbial benefits, such as anti-caries protection
and/or anti-gingivitis protection, and/or anti-erosion benefits for
protection of tooth enamel. Examples of suitable amounts of
stannous fluoride range from 0.05% by weight to 11% by weight, such
as from 0.05 to 7% by weight, or from 0.1% to 5% by weight, or from
0.2 to 3% by weight, or from 0.2 to 2% by weight, or from 0.2 to 1%
by weight, or from 0.2 to 0.8% by weight, or from 0.4 to 0.6% by
weight, or from 0.4 to 0.5% by weight, or about 0.45% by weight
(e.g., 0.454%), relative to the total weight of the dentifrice
composition. Formulations can include stannous levels, provided by
stannous fluoride, ranging for example, from 3,000 ppm to 15,000
ppm (mass fraction) stannous ions in the total composition. In
embodiments, the soluble stannous content can range from 0.1 wt %
to 0.5 wt %, or more, such as from 0.15 wt % to 0.32 wt %, based on
the total weight of the composition.
[0046] The combination of zinc and stannous ions provides one or
more of the following benefits: improved antimicrobial benefits
compared to the zinc ions alone; improved control of plaque and/or
gingivitis; improved protection against the erosion of tooth
enamel.
[0047] In compositions comprising significant amounts of water, the
zinc phosphate acts as a stabilizing agent for the stannous
fluoride, so that the stannous fluoride remains in solution in the
water. As discussed above, stannous fluoride is generally
considered unstable in water due to the hydrolytic and oxidative
loss of stannous ions at typical pH ranges employed in oral care
compositions. Consequently, stannous fluoride is generally employed
in compositions containing no water or low water, or with a
chelating agent. Tedious procedures are employed in order to
provide stable solutions in which the tendency of the stannous ion
to be oxidized or hydrolyzed is inhibited. Applicants have
surprisingly found that zinc phosphate and stannous fluoride can be
combined together in a single phase formulation using standard
mixing processes and typical pH ranges to form stable aqueous oral
care compositions. The zinc phosphate remains essentially insoluble
in the composition. However, the stannous fluoride has been shown
to remain soluble and stable in solutions comprising relatively
high amounts of water for extended periods of time, such as 3
months or longer at 40.degree. C. Under typical storage conditions,
the stannous fluoride is expected to remain sufficiently stable to
provide a desired shelf life of, for example, 1 to 2 years or
longer.
[0048] Any desired amount of water can be employed in the
compositions of the present disclosure. Examples of suitable
amounts of water range from 12% by weight or more, such as from 15%
to 98 or 99% by weight. For example, the amount of water may be
from 15% to 85%, or from 20% to 75%, or from 25% to 50%, or from
30% to 40%, for example, about 35%, by weight of the composition.
Amounts will vary depending on the type of oral care composition.
In an embodiment where the composition is a dentifrice, such as
toothpaste, the amount of water can range, for example, from 15% to
60% by weight, such as from 25% to 50%, or from 25% to 40% by
weight, relative to the total weight of the dentifrice
composition.
[0049] The amount of water in the compositions as set forth in the
above ranges includes both free water which is added separately
plus that amount that is introduced with the other ingredients.
Water employed in the preparation of the oral compositions of the
present disclosure can be deionized (sometimes referred to as
demineralized water) and/or free of organic impurities. Sources of
water beyond the directly added water include ingredients which are
commonly add as aqueous solutions, such as sorbitol (commonly
provided as a 70% w/w aqueous solution).
[0050] The compositions may optionally comprise additional
ingredients suitable for use in oral care compositions. Examples of
such ingredients include active agents, such as a fluoride source
and/or a phosphate source in addition to zinc phosphate. The
compositions may be formulated in a suitable dentifrice base, e.g.,
comprising abrasives, e.g., silica abrasives, surfactants, foaming
agents, vitamins, polymers, enzymes, humectants, thickeners,
additional antimicrobial agents, preservatives, flavorings,
colorings, and/or combinations thereof. Examples of suitable
dentifrice bases are known in the art. Alternatively, the
compositions may be formulated as a gel (e.g., for use in a tray),
chewing gum, lozenge or mint. Examples of suitable additional
ingredients that can be employed in the compositions of the present
disclosure are discussed in more detail below.
[0051] Active Agents: The compositions of the disclosure may
comprise various other agents that are active to protect and
enhance the strength and integrity of the enamel and tooth
structure and/or to reduce bacteria and associated tooth decay
and/or gum disease or to provide other desired benefits. Effective
concentration of the active ingredients used herein will depend on
the particular agent and the delivery system used. The
concentration will also depend on the exact salt or polymer
selected. For example, where the active agent is provided in salt
form, the counterion will affect the weight of the salt, so that if
the counterion is heavier, more salt by weight will be required to
provide the same concentration of active ion in the final
product.
[0052] Compositions of the disclosure may contain from 0.1 to 1 wt
% of an antibacterial agent, such as about 0.3 wt. %. Any suitable
antimicrobial actives can be employed.
[0053] Fluoride Ion Source: The oral care compositions can include
one or more additional fluoride ion sources, e.g., soluble fluoride
salts. A wide variety of fluoride ion-yielding materials can be
employed as sources of soluble fluoride in the present
compositions. Examples of suitable fluoride ion-yielding materials
are found in U.S. Pat. No. 3,535,421, to Briner et al.; U.S. Pat.
No. 4,885,155, to Parran, Jr. et al. and U.S. Pat. No. 3,678,154,
to Widder et al, the disclosure of each of which is hereby
incorporated by reference in their entirety. Representative
fluoride ion sources include, but are not limited to, sodium
fluoride, potassium fluoride, sodium monofluorophosphate, sodium
fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium
fluoride, and combinations thereof. In certain embodiments the
fluoride ion source includes sodium fluoride, sodium
monofluorophosphate as well as mixtures thereof. In certain
embodiments, the oral care composition of the disclosure may
contain stannous fluoride and any additional source of fluoride
ions or fluorine-providing agents in amounts sufficient to supply,
in total, from 25 ppm to 25,000 ppm (mass fraction) of fluoride
ions, generally at least 500 ppm, e.g., from 500 to 2000 ppm, e.g.,
from 1000 to 1600 ppm, e.g., about 1450 ppm. The appropriate level
of fluoride will depend on the particular application. A toothpaste
for general consumer use would typically have from 1000 to about
1500 ppm, with pediatric toothpaste having somewhat less. A
dentifrice or coating for professional application could have as
much as 5,000 or even about 25,000 ppm fluoride. Additional
fluoride ion sources may be added to the compositions of the
disclosure at a level of from 0.01 wt. % to 10 wt. % in one
embodiment or from 0.03 wt. % to 5 wt. %, and in another embodiment
from 0.1 wt. % to 1 wt. % by weight of the composition. As
discussed above, weights of fluoride salts to provide the
appropriate level of fluoride ion will vary based on the weight of
the counterion in the salt.
[0054] Abrasives: The compositions of the disclosure can include
abrasives. Examples of suitable abrasives include silica abrasives,
such as standard cleaning silicas, high cleaning silicas or any
other suitable abrasive silicas. Additional examples of abrasives
that can be used in addition to or in place of the silica abrasives
include, for example, a calcium phosphate abrasive, e.g.,
tricalcium phosphate (Ca.sub.3(PO.sub.4).sub.2), hydroxyapatite
(Ca.sub.10(PO.sub.4).sub.6(OH).sub.2), or dicalcium phosphate
dihydrate (CaHPO.sub.4.2H.sub.2O, also sometimes referred to herein
as DiCal) or calcium pyrophosphate; calcium carbonate abrasive; or
abrasives such as sodium metaphosphate, potassium metaphosphate,
aluminum silicate, calcined alumina, bentonite or other siliceous
materials, or combinations thereof.
[0055] Silica abrasive polishing materials useful herein, as well
as the other abrasives, generally have an average particle size
ranging between 0.1 and 30 microns, such as between 5 and 15
microns. The silica abrasives can be from precipitated silica or
silica gels, such as the silica xerogels described in U.S. Pat. No.
3,538,230, to Pader et al. and U.S. Pat. No. 3,862,307, to
Digiulio, the disclosures of which are incorporated herein by
reference in their entireties. Particular silica xerogels are
marketed under the trade name Syloid.RTM. by the W. R. Grace &
Co., Davison Chemical Division. The precipitated silica materials
include those marketed by the J. M. Huber Corp. under the trade
name Zeodent.RTM., including the silica carrying the designation
Zeodent 115 and 119. These silica abrasives are described in U.S.
Pat. No. 4,340,583, to Wason, the disclosure of which is
incorporated herein by reference in its entirety. In certain
embodiments, abrasive materials useful in the practice of the oral
care compositions in accordance with the disclosure include silica
gels and precipitated amorphous silica having an oil absorption
value of less than 100 cc/100 g silica, such as from 45 cc/100 g to
70 cc/100 g silica. Oil absorption values are measured using the
ASTA Rub-Out Method D281. In certain embodiments, the silicas are
colloidal particles having an average particle size of from 3
microns to 12 microns, and from 5 to 10 microns. Examples of low
oil absorption silica abrasives useful in the practice of the
disclosure are marketed under the trade designation Sylodent
XWA.RTM. by Davison Chemical Division of W.R. Grace & Co.,
Baltimore, Md. 21203. Sylodent 650 XWA.RTM., a silica hydrogel
composed of particles of colloidal silica having a water content of
29% by weight averaging from 7 to 10 microns in diameter, and an
oil absorption of less than 70 cc/100 g of silica is an example of
a low oil absorption silica abrasive useful in the practice of the
present disclosure.
[0056] Any suitable amount of silica abrasive can be employed.
Examples of suitable amounts include 10 wt. % or more dry weight of
silica particles, such as from 15 wt. % to 30 wt. % or from 15 wt.
% to 25 wt. %, based on the total weight of the composition.
[0057] Foaming agents: The oral care compositions of the disclosure
also may include an agent to increase the amount of foam that is
produced when the oral cavity is brushed. Illustrative examples of
agents that increase the amount of foam include, but are not
limited to polyoxyethylene and certain polymers including, but not
limited to, alginate polymers. The polyoxyethylene may increase the
amount of foam and the thickness of the foam generated by the oral
care compositions of the present disclosure. Polyoxyethylene is
also commonly known as polyethylene glycol ("PEG") or polyethylene
oxide. The polyoxyethylenes suitable for compositions of the
present disclosure may have a molecular weight of from 200,000 to
7,000,000. In one embodiment the molecular weight may be from
600,000 to 2,000,000 and in another embodiment from 800,000 to
1,000,000. Polyox.RTM. is the trade name for the high molecular
weight polyoxyethylene produced by Union Carbide. The foaming
agent, (e.g., polyoxyethylene) may be present in an amount of from
0.1% to 50%, in one embodiment from 0.5% to 20% and in another
embodiment from 1% to 10%, or from 2% to 5% by weight of the oral
care compositions of the present disclosure.
[0058] Surfactants: The compositions useful in the compositions of
the present disclosure may contain anionic surfactants, for
example: [0059] i. water-soluble salts of higher fatty acid
monoglyceride monosulfates, such as the sodium salt of the
monosulfated monoglyceride of hydrogenated coconut oil fatty acids
such as sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride
sulfate, [0060] ii. higher alkyl sulfates, such as sodium lauryl
sulfate, [0061] iii. higher alkyl-ether sulfates, e.g., of formula
CH.sub.3(CH.sub.2).sub.mCH.sub.2(OCH.sub.2CH.sub.2).sub.nOSO.sub.-
3X, wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X
is Na or K, for example sodium laureth-2 sulfate
(CH.sub.3(CH.sub.2).sub.10CH.sub.2(OCH.sub.2CH.sub.2).sub.2OSO.sub.3Na),
[0062] iv. higher alkyl aryl sulfonates such as sodium dodecyl
benzene sulfonate (sodium lauryl benzene sulfonate), [0063] v.
higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate
(dodecyl sodium sulfoacetate), higher fatty acid esters of 1,2
dihydroxy propane sulfonate, sulfocolaurate (N-2-ethyl laurate
potassium sulfoacetamide) and sodium lauryl sarcosinate.
[0064] By "higher alkyl" is meant, e.g., C.sub.6-30 alkyl. In
certain embodiments, the anionic surfactants useful herein include
the water-soluble salts of alkyl sulfates having from 10 to 18
carbon atoms in the alkyl radical and the water-soluble salts of
sulfonated monoglycerides of fatty acids having from 10 to 18
carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinate and
sodium coconut monoglyceride sulfonates are examples of anionic
surfactants of this type. In particular embodiments, the anionic
surfactant is selected from sodium lauryl sulfate and sodium ether
lauryl sulfate. In a particular embodiment, the compositions of the
disclosure comprise sodium lauryl sulfate. The anionic surfactant
may be present in an amount which is effective, e.g., >0.01% by
weight of the formulation, but not at a concentration which would
be irritating to the oral tissue, e.g., <10%, and optimal
concentrations depend on the particular formulation and the
particular surfactant. In one embodiment, the anionic surfactant is
present in a toothpaste at from 0.3% to 4.5% by weight, e.g., about
1.5%. The compositions of the disclosure may optionally contain
mixtures of surfactants, e.g., comprising anionic surfactants and
other surfactants that may be anionic, cationic, zwitterionic or
nonionic. Generally, suitable surfactants are those which are
reasonably stable throughout a wide pH range. Surfactants are
described more fully, for example, in U.S. Pat. No. 3,959,458, to
Agricola et al.; U.S. Pat. No. 3,937,807, to Haefele; and U.S. Pat.
No. 4,051,234, to Gieske et al, the disclosures of which are
incorporated herein by reference in their entireties.
[0065] The surfactant or mixtures of compatible surfactants that
are included in addition to the anionic surfactants can be present
in the compositions of the present disclosure in from 0.1% to 5.0%,
in another embodiment from 0.3% to 3.0% and in another embodiment
from 0.5% to 2.0% by weight of the total composition. These ranges
do not include the anionic surfactant amounts.
[0066] In an embodiment, the compositions of the present disclosure
include a zwitterionic surfactant, for example a betaine
surfactant, for example cocamidopropylbetaine, e.g. in an amount of
from 0.1% to 4.5% by weight, e.g. from 0.5 to 2% by weight
cocamidopropylbetaine.
[0067] Tartar control agents: In various embodiments of the present
disclosure, the compositions comprise an anticalculus (tartar
control) agent. Suitable anticalculus agents include without
limitation phosphates and polyphosphates (for example
pyrophosphates and tripolyphosphates), polyaminopropanesulfonic
acid (AMPS), hexametaphosphate salts, zinc citrate trihydrate,
polypeptides, polyolefin sulfonates, polyolefin phosphates, and
diphosphonates. The compositions of the disclosure thus may
comprise phosphate salts in addition to the zinc phosphate. In
particular embodiments, these salts are alkali phosphate salts,
e.g., salts of alkali metal hydroxides or alkaline earth
hydroxides, for example, sodium, potassium or calcium salts.
"Phosphate" as used herein encompasses orally acceptable mono- and
polyphosphates, for example, P.sub.1-6 phosphates, for example
monomeric phosphates such as monobasic, dibasic or tribasic
phosphate; and dimeric phosphates such as pyrophosphates; and
multimeric phosphates, such as tripolyphosphates, tetraphosphates,
hexaphosphates and hexametaphosphates (e.g., sodium
hexametaphosphate). In particular examples, the selected phosphate
is selected from alkali dibasic phosphate and alkali pyrophosphate
salts, e.g., selected from sodium phosphate dibasic, potassium
phosphate dibasic, dicalcium phosphate dihydrate, calcium
pyrophosphate, tetrasodium pyrophosphate, tetrapotassium
pyrophosphate, sodium tripolyphosphate, and mixtures of any of two
or more of these. In a particular embodiment, for example the
compositions may comprise tetrasodium pyrophosphate in an amount of
from 0.5 to 5% by weight, e.g., 1-3%, or 1-2% or about 2% by weight
of the composition. In another embodiment, the compositions may
comprise a mixture of tetrasodium pyrophosphate (TSPP) and sodium
tripolyphosphate (STPP), e.g., in proportions of TSPP at from 0.5
to 5 wt. %, such as from 1 to 2 wt. % and STPP at from 0.5% to 6
wt. %, such as 1 to 4%, or 2 to 3% by weight of the composition.
Such phosphates are provided in an amount effective to reduce
erosion of the enamel, to aid in cleaning the teeth, and/or to
reduce tartar buildup on the teeth, for example in an amount of
from 0.2 to 20 wt. %, e.g., from 1 to 15 wt. %, by weight of the
composition.
[0068] Flavoring Agents: The oral care compositions of the
disclosure may also include a flavoring agent. Flavoring agents
which are used in the practice of the present disclosure include,
but are not limited to, essential oils as well as various flavoring
aldehydes, esters, alcohols, and similar materials. Examples of the
essential oils include oils of spearmint, peppermint, wintergreen,
sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon,
lime, grapefruit, and orange. Also useful are such chemicals as
menthol, carvone, and anethole. Certain embodiments employ the oils
of peppermint and spearmint. The flavoring agent may be
incorporated in the oral composition at a concentration of from 0.1
to 5% by weight e.g., from 0.5 to 1.5% by weight.
[0069] Polymers: The oral care compositions of the disclosure may
also include additional polymers to adjust the viscosity of the
formulation or enhance the solubility of other ingredients. Such
additional polymers include polyethylene glycols, polysaccharides
(e.g., cellulose derivatives, for example carboxymethyl cellulose,
microcrystalline cellulose or polysaccharide gums, for example
xanthan gum or carrageenan gum). Acidic polymers, for example
polyacrylate gels, may be provided in the form of their free acids
or partially or fully neutralized water soluble alkali metal (e.g.,
potassium and sodium) or ammonium salts. In one embodiment, the
oral care composition may contain PVP. PVP generally refers to a
polymer containing vinylpyrrolidone (also referred to as
N-vinylpyrrolidone, N-vinyl-2-pyrrolidione and
N-vinyl-2-pyrrolidinone) as a monomeric unit. The monomeric unit
consists of a polar imide group, four non-polar methylene groups
and a non-polar methane group.
[0070] Silica thickeners, which form polymeric structures or gels
in aqueous media, may be present. Note that these silica thickeners
are physically and functionally distinct from the particulate
silica abrasives also present in the compositions, as the silica
thickeners are very finely divided and provide little or no
abrasive action. Other thickening agents are carboxyvinyl polymers,
carrageenan, hydroxyethyl cellulose and water soluble salts of
cellulose ethers such as sodium carboxymethyl cellulose and sodium
carboxymethyl hydroxyethyl cellulose. Natural gums such as karaya,
gum arabic, and gum tragacanth can also be incorporated. Colloidal
magnesium aluminum silicate can also be used as component of the
thickening composition to further improve the composition's
texture. In certain embodiments, thickening agents in an amount of
from 0.5% to 5.0% by weight of the total composition are used.
[0071] The compositions of the disclosure may include an anionic
polymer, for example in an amount of from 0.05 to 5%. Examples of
such agents generally known for use in dentifrice are disclosed in
U.S. Pat. Nos. 5,188,821 and 5,192,531, both of which are
incorporated herein by reference in their entirety; and include
synthetic anionic polymeric polycarboxylates, such as 1:4 to 4:1
copolymers of maleic anhydride or acid with another polymerizable
ethylenically unsaturated monomer, preferably methyl vinyl
ether/maleic anhydride having a molecular weight (M.W.) of from
30,000 to 1,000,000, such as from 300,000 to 800,000. These
copolymers are available for example as Gantrez, e.g., AN 139 (M.W.
500,000), AN 119 (M.W. 250,000) and preferably S-97 Pharmaceutical
Grade (M.W. 700,000) available from ISP Technologies, Inc., Bound
Brook, N.J. 08805. The enhancing agents when present are present in
amounts ranging from 0.05 to 3% by weight. Other operative polymers
include those such as the 1:1 copolymers of maleic anhydride with
ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone,
or ethylene, the latter being available for example as Monsanto EMA
No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1 copolymers of
acrylic acid with methyl or hydroxyethyl methacrylate, methyl or
ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.
Suitable generally, are polymerized olefinically or ethylenically
unsaturated carboxylic acids containing an activated
carbon-to-carbon olefinic double bond and at least one carboxyl
group, that is, an acid containing an olefinic double bond which
readily functions in polymerization because of its presence in the
monomer molecule either in the alpha-beta position with respect to
a carboxyl group or as part of a terminal methylene grouping.
Illustrative of such acids are acrylic, methacrylic, ethacrylic,
alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic,
alpha-chlorsorbic, cinnamic, beta-styrylacrylic, muconic, itaconic,
citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic,
2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric,
maleic acids and anhydrides. Other different olefinic monomers
copolymerizable with such carboxylic monomers include vinylacetate,
vinyl chloride, dimethyl maleate and the like. Copolymers contain
sufficient carboxylic salt groups for water-solubility. A further
class of polymeric agents includes a composition containing
homopolymers of substituted acrylamides and/or homopolymers of
unsaturated sulfonic acids and salts thereof, in particular where
polymers are based on unsaturated sulfonic acids selected from
acrylamidoalykane sulfonic acids such as 2-acrylamide 2
methylpropane sulfonic acid having a molecular weight of from 1,000
to 2,000,000. Another useful class of polymeric agents includes
polyamino acids containing proportions of anionic surface-active
amino acids such as aspartic acid, glutamic acid and phosphoserine,
e.g. as disclosed in U.S. Pat. No. 4,866,161, issued to Sikes et
al., which is also incorporated herein by reference in its
entirety.
[0072] Humectants: Within certain embodiments of the oral
compositions, it is also desirable to incorporate a humectant to
prevent the composition from hardening upon exposure to air.
Certain humectants can also impart desirable sweetness or flavor to
dentifrice compositions. Suitable humectants include edible
polyhydric alcohols such as glycerin, sorbitol, xylitol, propylene
glycol as well as other polyols and mixtures of these humectants.
In one embodiment of the disclosure, the principal humectant is one
of glycerin, sorbitol or a combination thereof. The humectant may
be present at levels of greater than 15 wt. %, such as from 15 wt.
% to 55 wt. %, or from 20 wt. % to 50 wt. %, or from 20 wt. % to 40
wt. %, or about 20% or about 30% or about 40%, based on the total
weight of the composition.
[0073] Other optional ingredients: In addition to the
above-described components, the embodiments of this disclosure can
contain a variety of optional oral care ingredients some of which
are described below. Optional ingredients include, for example, but
are not limited to, adhesives, sudsing agents, flavoring agents,
sweetening agents such as sodium saccharin, additional antiplaque
agents, abrasives, aesthetics such as TiO.sub.2 coated mica or
other coloring agents, such as dyes and/or pigments.
[0074] In an embodiment, the compositions of the present disclosure
can have any pH suitable for in a product for use in oral care.
Examples of suitable pH ranges are from 6 to 9, such as from 6.5 to
8.
[0075] In an embodiment, the oral care compositions of the present
disclosure are either essentially free of or do not include any
sodium hexametaphosphate, such as is used in the compositions of
U.S. Pat. No. 3,095,356, the disclosure of which is incorporated
herein by reference in its entirety. In an embodiment, the oral
care compositions of the present disclosure are either essentially
free of or do not include any of a halogenated diphenyl ether, such
as those recited in U.S. Patent Application Publication No.
2013/0216485, the disclosure of which is incorporated herein by
reference in its entirety. In an embodiment, the oral care
compositions of the present disclosure are either essentially free
of or do not include any of TRPV1 activators and/or vanitrope, as
used in the compositions taught in CA 2760445, the disclosure of
which is incorporated herein by reference in its entirety. In an
embodiment, the oral care compositions of the present disclosure
are either essentially free of or do not include any of a high
intensity sweetener selected from the group consisting of
trichloro-sucrose (sucralose), acesulfame, neohesperidine DC,
thaumatin, glycyrrhizin, mogroside IV, mogroside V, cyclocarioside
I,N--[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-.alpha.-aspartyl]-L-pheny-
lalanine 1-methyl ester,
N--[N-[3-(3-hydroxy-4-methoxyphenyl)-3-methyl-butyl]-L-.alpha.-aspartyl]--
L-phenylalanine 1-methyl ester,
N--[N-[3-(3-methoxy-4-hydroxyphenyl)-propyl]-L-.alpha.-aspartyl]-L-phenyl-
alanine 1-methyl ester, and mixtures thereof. In an embodiment, the
compositions of the present disclosure are either essentially free
of or do not include any of a high intensity sweetener having a 10%
sucrose equivalence of from 500-600, as disclosed in U.S. Patent
Application Publication No. 2012/0082630, the disclosure of which
is herein incorporated by reference in its entirety. By
"essentially free" is meant that the compositions have no more than
0.01% by weight of these compounds.
[0076] In an embodiment, the compositions of the present disclosure
are either essentially free of or do not include any complexing
agents for increasing solubility of zinc phosphate and/or for
maintaining the stannous fluoride in solution. Examples of known
complexing agents that can be excluded from the compositions of the
present disclosure include the chelating agents taught in U.S.
Patent Application No. 2007/0025928, the disclosure of which is
hereby incorporated by reference in its entirety. Such chelating
agents include mineral surface-active agents, including mineral
surface-active agents that are polymeric and/or polyelectrolytes
and that are selected from phosphorylated polymers, wherein if the
phosphorylated polymer is a polyphosphate, the polyphosphate has
average chain length of 3.5 or more, such as 4 or more;
polyphosphonates; polycarboxylates; carboxy-substituted polymers;
copolymers of phosphate- or phosphonate-containing monomers or
polymers with ethylenically unsaturated monomers, amino acids,
proteins, polypeptides, polysaccharides, poly(acrylate),
poly(acrylamide), poly(methacrylate), poly(ethacrylate),
poly(hydroxyalkylmethacrylate), poly(vinyl alcohol), poly(maleic
anhydride), poly(maleate) poly(amide), poly(ethylene amine),
poly(ethylene glycol), poly(propylene glycol), poly(vinyl acetate)
and poly(vinyl benzyl chloride); and mixtures thereof. Other known
complexing agents that can be excluded from the compositions of the
present disclosure include those taught in CA 2634758, the
disclosure of which is incorporated here by reference in its
entirety. Examples include polyphosphorylated inositol compounds
such as phytic acid, myo-inositol pentakis(dihydrogen phosphate);
myo-inositol tetrakis(dihydrogen phosphate), myo-inositol
trikis(dihydrogen phosphate), and alkali metal, alkaline earth
metal or ammonium salts of any of the above inositol compounds.
Phytic acid is also known as myo-inositol 1,2,3,4,5,6-hexakis
(dihydrogen phosphate) or inositol hexaphosphoric acid.
[0077] The present application further discloses methods of using
the compositions described herein to increase zinc levels in the
enamel and to treat, reduce or control the incidence of enamel
erosion. The methods comprise applying any of the compositions as
described herein to the teeth, e.g., by brushing, or otherwise
administering the compositions to the oral cavity of a subject in
need thereof. The compositions can be administered regularly, such
as, for example, one or more times per day. In various embodiments,
administering the compositions of the present disclosure to a
patient can provide one or more of the following benefits: (i)
reduce hypersensitivity of the teeth, (ii) reduce plaque
accumulation, (iii) reduce or inhibit demineralization and promote
remineralization of the teeth, (iv) inhibit microbial biofilm
formation in the oral cavity, (v) reduce or inhibit gingivitis,
(vi) promote healing of sores or cuts in the mouth, (vii) reduce
levels of acid producing bacteria, (viii) increase relative levels
of non-cariogenic and/or non-plaque forming bacteria, (ix) reduce
or inhibit formation of dental caries, (x) reduce, repair or
inhibit pre-carious lesions of the enamel, e.g., as detected by
quantitative light-induced fluorescence (QLF) or electrical caries
measurement (ECM), (xi) treat, relieve or reduce dry mouth, (xii)
clean the teeth and oral cavity, (xiii) reduce erosion, (xiv)
whiten teeth; (xv) reduce tartar build-up, and/or (xvi) promote
systemic health, including cardiovascular health, e.g., by reducing
potential for systemic infection via the oral tissues. The
disclosure further provides compositions for use in any of the
above methods. Further embodiments provide methods wherein at least
one tooth is remineralized after administration of a composition as
described herein.
[0078] Compositions according to the present invention can be made
by the methods and procedures known to those skilled in the
art.
[0079] The present application further discloses a method of making
any of the compositions of the present disclosure. The method
comprises combining zinc phosphate and stannous fluoride in water
to form an aqueous zinc phosphate mixture having a water
concentration of 12% or more and a pH ranging from 6 to 9, such as
from 6.5 to 8. In some embodiments, the zinc phosphate is added to
the dentifrice composition as a preformed salt and remains
essentially insoluble in the aqueous mixture. The amount of water
employed in the mixture can be any of the amounts recited herein
for the compositions of the present disclosure. Any standard mixing
techniques can be employed to combine the ingredients and form a
stable composition without the need for additional complexing
agents to solubilize the stannous fluoride, such as any of the
above disclosed complexing or chelating agents, or the use of
anhydrous mixing techniques such as dissolving stannous fluoride in
an anhydrous material such as glycerin.
EXAMPLES
Example 1--Dentifrice Formulation
[0080] Test dentifrice comprising 1% zinc phosphate and 0.454%
stannous fluoride is prepared in accordance with the following
formulation of Table 1. Ingredients are listed by weight of the
composition.
TABLE-US-00001 TABLE 1 Ingredient Wt. % Water Q.S. (e.g., 15-40)
Thickener 0.5-5 (e.g. 3.6) Humectants 15-55 (e.g. 48) Tartar
Control Agents 0.5-5 (e.g. 2) Abrasives 10-30 (e.g. 20) Stannous
fluoride 0.05-11 (e.g. 0.454) Minors (flavor, color) 0.5-5 (e.g.
2.25) Surfactants 0.1-15 (e.g. 2.75) Zinc Phosphate 0.05-5 (e.g. 1
or 2)
Example 2--Stability Data
[0081] Three separate dentifrice samples of a formulation similar
to the formulation shown in Table 1 (above) are made. The three
samples are held at three different temperatures: room temperature
(approximately 25.degree. C.), approximately 40.degree. C. and
approximately 49.degree. C., for a period of three months. The
initial fluoride concentration for each sample is measured at the
beginning of the study and is then periodically measured after each
month of the study. The results show that in the presence of zinc
phosphate, fluoride concentrations remain sufficiently stable at
all three temperatures for a period of three months.
[0082] The data shows that by simply combining stannous fluoride
and zinc phosphate, a stable formulation can be achieved that
provides good anti-microbial benefits without the need for
employing techniques typically used for stabilizing stannous
fluoride compositions in water.
Example 3
[0083] An Example 3 dentifrice is made by adding 0.454% by weight
stannous fluoride to a commercially available toothpaste. As a
first control sample, a commercially available toothpaste without
stannous fluoride is used. Both the Example 3 toothpaste and the
first control sample have a zinc phosphate concentration of 1% by
weight. Another commercially available fluoride toothpaste, which
includes 1100 ppm (mass fraction) fluoride and 1 wt % zinc citrate,
is used as a second control sample.
[0084] An in vitro methodology is used to determine the enamel
protection activity of the formulation prototype of Example 3.
Enamel substrates (N=6/8 per cell) are prepared by embedding bovine
incisors in a methacrylate-based resin and polishing with 600 and
1200 grit carbide paper consecutively. Care is taken not to
penetrate the dentin layer while polishing the enamel to a mirror
finish. Prior to testing, all enamel substrates are pre-etched with
5% citric acid for 30 seconds. Half the side of each substrate is
masked with acid resistant tape to protect the surface as control
surface. The model used to evaluate the products alternated 1-min
product treatment periods with 2-min acid exposure periods
according to the daily sequence of T-C-C-C-C-T (T=product
treatment, C=acid challenge). The acid challenge is performed with
a 1% aqueous solution of citric acid (unbuffered) adjusted to
pH=3.8 with NaOH. All enamel substrates are kept in a sterile
artificial saliva solution at 37.degree. C. while not undergoing
treatment or challenge. This regimen is conducted for a total of
five days, at the end of which a microhardness analysis is used to
quantify the amount of enamel lost due to erosion on each enamel
substrate on the protected and exposed surface. The change in
percentage hardness is calculated. Without treatment, using
deionized water in place of test dentifrice, the change in
percentage hardness is very high, ca. 80%, with slight variation
from experiment to experiment depending on the particular
substrate.
[0085] The dentifrice of Example 3 and both control samples are
tested using the above procedure. The Example 3 formula containing
both zinc phosphate and stannous fluoride is effective against
demineralization in this in vitro pH-cycling model designed to
investigate the protective effect of treatments on early enamel
dissolution, with an average reduction in hardness following
repeated acid challenges of only about 89.4 g.sub.fmm.sup.-2. This
is greater than the average 83.32 g.sub.fmm.sup.-2 reduction in
hardness seen for the first control sample using zinc phosphate
without stannous fluoride, but is still significantly better than
the results for the second control sample, which gave an average
reduction in hardness of about 98.5 g.sub.fmm.sup.-2. Hardness here
is determined by the Knoop Hardness HK test. Thus the enamel
protection activity of the zinc phosphate and stannous fluoride
formulation of Example 3 is considered to be excellent.
Example 4
[0086] A demineralization/remineralization study of two commercial
comparative compositions (Comp. Ex. I and II) and an exemplary
composition of the present invention (Example 4) is conducted on
bovine teeth. The formulations of Comparative Ex. I and Example 4
are provided below in Table 2. Comparative Example II is a
commercial sodium fluoride toothpaste which contains no zinc or
stannous agents.
TABLE-US-00002 TABLE 2 Ingredient % w/w Example 4 Comp. Ex. I Water
and minors 11.74 9.50 (color, flavor) Stannous fluoride 0.454 0.454
Zinc lactate -- 2.50 Zinc phosphate 1.15 -- Thickeners 2.9 3.15
Glycerin 40.79 34.65 Abrasive silica 24.00 20.00 Sodium -- 13.00
Hexametaphosphate Propylene Glycol 4.00 7.00 Trisodium Citrate 3.00
-- Dihydrate Sodium 3.00 -- Tripolyphosphate Polyethylene Glycol
3.00 7.00 600 Tetrasodium 2.00 -- Pyrophosphate Anionic Surfactant
1.75 1.00 Trisodium Phosphate -- 1.10 Zwitterionic 1.00 --
Surfactant Sodium Gluconate -- 0.65 Anionic Polymer 0.61 -- Citric
Acid 0.60 --
[0087] Bovine teeth are soaked in heated saliva overnight to form a
pellicle. The teeth are then treated twice a day for ten (10) days
with a 1:2 toothpaste:water slurry and subjected to two minute acid
challenges with a 1% citric acid solution.
[0088] As illustrated by the data described in Table 3 (below),
only the exemplary composition of the present disclosure
demonstrates an ability to actually remineralize enamel, while the
comparative examples could not deliver the same benefit.
TABLE-US-00003 TABLE 3 Composition % Mineral Loss Example 4 (-)
4.07 Comp. Ex. I 53.12 Comp. Ex. 71.29
Example 5
[0089] A 13-week stability study is performed with two arms, one at
room temperature and one at 40.degree. C. Formulation A-1 is a
dentifrice containing 0.454% stannous fluoride, 1% zinc phosphate,
1.2% citrate buffer, and 4% TSPP. Formulation B contains 0.454%
stannous fluoride, 1% zinc oxide, 1.2% citrate buffer, and 4% TSPP.
The results are shown in Table 4 below.
TABLE-US-00004 TABLE 4 Soluble Fluoride (ppm) Soluble Tin (wt %)
Soluble Zinc (wt %) 8 weeks 13 Weeks 8 weeks 13 Weeks 8 weeks 13
Weeks Initial RT 40.degree. C. Initial RT 40.degree. C. Initial RT
40.degree. C. Form. A-1 1099 1080 1011 0.27 0.26 0.20 0.33 0.36
0.29 Form. B 1124 1138 1136 0.07 0.00 0.00 0.44 0.32 0.22
[0090] The results demonstrate that while the use of zinc oxide
results in comparable fluoride stability to using zinc phosphate,
the soluble stannous level and soluble zine level is significantly
reduced both initially and over the course of the study when zinc
oxide is used instead of zinc phosphate. This demonstrates that
zinc phosphate has the ability to stabilize stannous ion against
oxidative degradation, whereas zinc oxide does not. Without being
bound by theory, it is believed that zinc oxide when solubilized
can adversely interact with stannous fluoride to cause conversion
of the stannous ion to stannous hydroxide, which precipitates out.
In contrast, zinc phosphate is able to maintain zinc and stannous
in a bioavailable soluble form.
Example 6
[0091] An additional stability study is performed in which the
soluble tin recoverable is compared between a formulation according
to the present invention (Formulation A-2) and two commercial
competitors (Comparative B and C). The study is performed for 13
weeks at room temperature. Formulation A-2 comprises 0.454%
stannous fluoride, 1% zinc phosphate, 1.2% citrate buffer, and 2%
TSPP (Formula A-2 is essentially the same as Formulation A-1,
except that it contains 2% TSPP instead of 4% TSPP). Comparative
composition B is a low water composition comprising 0.454% stannous
fluoride, about 2.5% zinc lactate, and about 10% water. Comparative
composition C is a high-water composition comprising 0.454%
stannous fluoride, 0.27% stannous chloride, 0.5% zinc citrate, and
about 43% water. The results shown in Table 5 below demonstrate
that while existing low-water stannous fluoride compositions can
achieve stannous ion stability, high water compositions cannot.
Indeed, the commercial formulation comprising more than double the
total tin salt content results in half as much recoverable soluble
tin at the conclusion of the study.
TABLE-US-00005 TABLE 5 Total Added Soluble Tin at 13 Tin (wt %)
Weeks (wt %) Formulation A-2 0.34 0.22 Comparative B 0.34 0.20 (low
water) Comparative C 0.72 0.10 (high water)
Example 7
[0092] Tin can exist in two oxidation states, Sn(II) (stannous) and
Sn(IV) (stannic). Oxidizing agents, including atmospheric oxygen,
can oxidize Sn(II) to Sn(IV). Soluble Sn(II) can be rapidly
quantified by titrating with the inorganic oxidizing agent iodine,
such as according to the method of Howe, P., and Watts, P., Tin and
inorganic tin compounds, (World Health Organization, 2005).
Formulation A-2, and Comparative Formulations B and C, as described
above, are tested for soluble tin using this method. The results
are shown in Table 6 below. These results further demonstrate that
a composition according to the invention unexpectedly stabilizes
tin in a high water composition.
TABLE-US-00006 TABLE 6 Tin (II) (Wt %) Formulation A-2 0.25
Comparative B (low 0.13 water) Comparative C (high 0.16 water)
Example 8
[0093] The antibacterial efficacy of Formulation A-2 is compared to
various commercial competitor formulations using the planktonic
bacteria ATP luminescence assay described in Example 3. Formulation
A-2 is a dentifrice comprising 0.454% stannous fluoride, 1% zinc
phosphate, 1.2% citrate buffer, and 2% TSPP. Comparative
composition C is a high-water composition comprising 0.454%
stannous fluoride, 0.27% stannous chloride, 0.5% zinc citrate, and
about 43% water. Comparative Composition D is a commercial
stabilized stannous dentifrice comprising about 0.45% stannous
fluoride in a substantially anhydrous (zero-water) base. The
results are shown in Table 7 below. Samples are diluted 1:8 in a
mixture of saliva and PBS. Positive controls are measured for
saliva alone and the saliva/PBS mixture used for sample dilution.
The results show that Formulation A-2 is significantly more
effective in killing bacteria compared to any of the commercial
competitors.
TABLE-US-00007 TABLE 7 Luminescence (cps) Saliva (Control) 168398
Saliva/PBS 109810 (Control) Formulation A-2 4954 Comparative C
65192 (high water) Comparative D 11612 (no water)
[0094] While the present invention has been described with
reference to embodiments, it will be understood by those skilled in
the art that various modifications and variations may be made
therein without departing from the scope of the present invention
as defined by the appended claims.
* * * * *