U.S. patent application number 17/752568 was filed with the patent office on 2022-09-08 for aliphatic anionic compounds and oxidative compounds with improved stability and efficacy for use in pharmaceutical compositions.
This patent application is currently assigned to Micropure, Inc.. The applicant listed for this patent is Micropure, Inc.. Invention is credited to William E. Cooley, Esmeralda Ann Garcia-Smith, James L. Ratcliff, Jaiprakash G. Shewale.
Application Number | 20220280402 17/752568 |
Document ID | / |
Family ID | 1000006351561 |
Filed Date | 2022-09-08 |
United States Patent
Application |
20220280402 |
Kind Code |
A1 |
Shewale; Jaiprakash G. ; et
al. |
September 8, 2022 |
ALIPHATIC ANIONIC COMPOUNDS AND OXIDATIVE COMPOUNDS WITH IMPROVED
STABILITY AND EFFICACY FOR USE IN PHARMACEUTICAL COMPOSITIONS
Abstract
Various embodiments described herein provide for a
multi-component compositions and methods for its pharmaceutical and
cosmetic use, comprising a combination of an aliphatic anionic
compound, an oxidative compound, and a buffering system. Source of
fluoride ion and other carriers are optional ingredients. The
aliphatic anionic compound and the oxidative compound function
together, in presence or absence of fluoride ion source, to protect
the oxidative compounds from degradation prior to use and upon use,
and to enhance the efficacy of the composition. In addition to
achieving greater stability, combined effects of the aliphatic
anionic compound, oxidative compound and source of fluoride ion
achieve enhanced fluoride uptake, higher enamel protection by
enhanced remineralization and reduced demineralization, increased
plaque removal, reduced re-growth of plaque polymicrobial biofilm,
greater amount of chlorite ion availability and effective oxidation
of salivary biomolecules.
Inventors: |
Shewale; Jaiprakash G.;
(Cave Creek, AZ) ; Cooley; William E.; (Wyoming,
OH) ; Ratcliff; James L.; (Scottsdale, AZ) ;
Garcia-Smith; Esmeralda Ann; (Centerton, AR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Micropure, Inc. |
Scottsdale |
AZ |
US |
|
|
Assignee: |
Micropure, Inc.
Scottsdale
AZ
|
Family ID: |
1000006351561 |
Appl. No.: |
17/752568 |
Filed: |
May 24, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16133359 |
Sep 17, 2018 |
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17752568 |
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PCT/US2018/049302 |
Sep 3, 2018 |
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16133359 |
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62676170 |
May 24, 2018 |
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62553450 |
Sep 1, 2017 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/442 20130101;
A61Q 11/00 20130101; A61K 8/21 20130101; A61K 8/20 20130101; A61K
8/24 20130101 |
International
Class: |
A61K 8/44 20060101
A61K008/44; A61K 8/20 20060101 A61K008/20; A61K 8/21 20060101
A61K008/21; A61K 8/24 20060101 A61K008/24; A61Q 11/00 20060101
A61Q011/00 |
Claims
1. A method for effecting enhanced fluoride uptake into the tooth
enamel, comprising: preparing an oral care single phase composition
comprising from about 0.01% to about 5.0% of an aliphatic anionic
compound, based on a total weight of the composition, from about
0.001 to about 8.0% of an oxidative compound, based on a total
weight of the composition, from about 0.01% to 0.8% of fluoride ion
source, based on a total weight of the composition, a buffering
system, wherein pH of the oral care single phase composition is
between 6.0 and 8.0, water, wherein the aliphatic anionic compound
provides enhanced stability for the oxidative compound, wherein the
oxidative compound is sodium chlorite, wherein the buffering system
comprises disodium hydrogen phosphate and sodium dihydrogen
phosphate, wherein the aliphatic anionic compound is an N-acyl
sarcosinate, wherein the N-acyl sarcosinate is at least one of
sodium lauroyl sarcosinate, sodium cocoyl sarcosinate, sodium
myristoyl sarcosinate, sodium oleoyl sarcosinate, or sodium
stearoyl sarcosinate, wherein the composition exhibits less than
35% loss of the oxidative compound for a period of 24 months at
about 25.degree. C.; and applying the oral care single phase
composition to the oral cavity.
2. The method of claim 1, wherein the enhanced fluoride uptake into
the tooth enamel is increased by up to 4-fold.
3. The method of claim 1, further comprising adding, to the oral
care single phase composition, an orally acceptable aqueous vehicle
comprising at least one of a humectant, an abrasive, a
pharmaceutically acceptable carrier, a fluoride ion source, and a
thickening agent.
4. The method of claim 1, further comprising formulating the oral
care single phase composition into a form of, at least one of, a
mouth rinse, a gum, a gel, a paste, a cream, spray, and a
lozenge.
5. A method for effecting enhanced remineralization of the tooth
enamel, comprising: preparing an oral care single phase composition
comprising from about 0.01% to about 5.0% of an aliphatic anionic
compound, based on a total weight of the composition, from about
0.001 to about 8.0% of an oxidative compound, based on a total
weight of the composition, from about 0.01% to 0.8% of fluoride ion
source, based on a total weight of the composition, a buffering
system, wherein pH of the oral care single phase composition is
between 6.0 and 8.0, water, wherein the aliphatic anionic compound
provides enhanced stability for the oxidative compound, wherein the
oxidative compound is sodium chlorite, wherein the buffering system
comprises disodium hydrogen phosphate and sodium dihydrogen
phosphate, wherein the aliphatic anionic compound is an N-acyl
sarcosinate, wherein the N-acyl sarcosinate is at least one of
sodium lauroyl sarcosinate, sodium cocoyl sarcosinate, sodium
myristoyl sarcosinate, sodium oleoyl sarcosinate, or sodium
stearoyl sarcosinate, wherein the composition exhibits less than
35% loss of the oxidative compound for a period of 24 months at
about 25.degree. C.; and applying the oral care single phase
composition to the oral cavity.
6. The method of claim 5, wherein the enhanced remineralization of
the tooth enamel is increased by up to 2-fold.
7. The method of claim 5, further comprising adding, to the oral
care single phase composition, an orally acceptable aqueous vehicle
comprising at least one of: a humectant, an abrasive, a
pharmaceutically acceptable carrier, a fluoride ion source, and a
thickening agent.
8. The method of claim 5, further comprising formulating the oral
care single phase composition into a form of, at least one of, a
mouth rinse, a gum, a gel, a paste, a cream, spray, and a
lozenge.
9. A method for decreasing and delaying the regrowth of oral
polymicrobial biofilm, comprising: applying, to an oral cavity, an
oral care single phase composition comprising from about 0.01% to
about 5.0% of an aliphatic anionic compound, based on a total
weight of the composition, from about 0.001 to about 8.0% of an
oxidative compound, based on a total weight of the composition,
from about 0.01% to 0.8% of fluoride ion source, based on a total
weight of the composition, a buffering system, wherein pH of the
composition is between 6.0 and 8.0, water, wherein the aliphatic
anionic compound provides enhanced stability for the oxidative
compound, wherein the oxidative compound is sodium chlorite,
wherein the buffering system comprises disodium hydrogen phosphate
and sodium dihydrogen phosphate, wherein the aliphatic anionic
compound is an N-acyl sarcosinate, wherein the N-acyl sarcosinate
is at least one of sodium lauroyl sarcosinate, sodium cocoyl
sarcosinate, sodium myristoyl sarcosinate, sodium oleoyl
sarcosinate, or sodium stearoyl sarcosinate, wherein the
composition exhibits less than 35% loss of the oxidative compound
for a period of 24 months at about 25.degree. C.
10. The method of claim 9, wherein the oral care single phase
composition decreases oral polymicrobial biofilm and delays its
regrowth for up to 24 hours.
11. The method of claim 9, wherein the oral care single phase
composition further comprises an orally acceptable aqueous vehicle
comprising at least one of a humectant, an abrasive, a
pharmaceutically acceptable carrier, a fluoride ion source, and a
thickening agent.
12. The method of claim 9, wherein the oral care single phase
composition is formulated into a form of, at least one of, a mouth
rinse, a gum, a gel, a paste, a cream, spray, and a lozenge.
13. A method for oxidizing salivary biomolecules, comprising:
preparing an oral care single phase composition comprising from
about 0.01% to about 5.0% of an aliphatic anionic compound, based
on a total weight of the composition, from about 0.001 to about
8.0% of an oxidative compound, based on a total weight of the
composition, from about 0.01% to 0.8% of fluoride ion source, based
on a total weight of the composition, a buffering system, wherein
pH of the composition is between 6.0 and 8.0, water, wherein the
aliphatic anionic compound provides enhanced stability for the
oxidative compound, wherein the oxidative compound is sodium
chlorite, wherein the buffering system comprises disodium hydrogen
phosphate and sodium dihydrogen phosphate, wherein the aliphatic
anionic compound is an N-acyl sarcosinate, wherein the N-acyl
sarcosinate is at least one of sodium lauroyl sarcosinate, sodium
cocoyl sarcosinate, sodium myristoyl sarcosinate, sodium oleoyl
sarcosinate, or sodium stearoyl sarcosinate, wherein the
composition exhibits less than 35% loss of the oxidative compound
for a period of 24 months at about 25.degree. C.
14. The method of claim 13, wherein the salivary biomolecules are
comprised of at least one of pyruvate and L-methionine. 21. The
method of claim 18, further comprising oxidizing a salivary
biomolecule comprising at least one of pyruvate and L-methionine
within 30 to 60 seconds of contact time.
15. The method of claim 13, further comprising adding, to the oral
care single phase composition, an orally acceptable aqueous vehicle
comprising at least one of the following: a humectant, an abrasive,
a pharmaceutically acceptable carrier, a fluoride ion source, and a
thickening agent.
16. The method of claim 14, further comprising formulating the oral
care single phase composition into a form of, at least one of the
following: a mouth rinse, a gum, a gel, a paste, a cream, spray,
and a lozenge.
17. A method for preparation of oral care single phase toothpaste
composition comprising: dissolving a gelling agent in water in a
tank equipped with a stirring system to form an aqueous solution;
adding a buffering compound until a pH range of between 6.0 to 8.5
is achieved; adding the chlorite ion source to the aqueous
solution; adding at least one additional ingredient comprising at
least of a humectant, a sweetening agent, a coloring agent, an
abrasive agent, a fluoride ion source, a flavoring agent, an
emollient agent, a suspending agent, an emulsifying agent, an
N-acyl sarcosinate, or water; stirring the composition for about
40- to 60-minutes under vacuum; releasing the vacuum; and filling
the composition in a container for use, wherein all compounding
operations occur at ambient temperature.
18. A method of claim 17, wherein the composition is a gel or
cream.
19. A method for preparation of oral care single phase rinse
composition comprising: dissolving a base compound in water in a
tank equipped with a stirring system to form an aqueous solution;
adding the chlorite ion source to the aqueous solution; adding at
least one additional ingredient comprising at least one of a
sweetening agent, a fluoride ion source, a flavoring agent, an
N-acyl sarcosinate, and water' adding a weak acid compound until a
final pH range of 6.0 to 8.5 is achieved; stirring the composition
for about 40- to 60-minutes; and filling the composition in a
container for use, wherein all compounding operations occur at
ambient temperature.
20. A method for preparation of oral care single phase spray
composition comprising; dissolving a base compound in water in a
tank equipped with a stirring system to form an aqueous solution;
adding a chlorite ion source to the aqueous solution; adding at
least one additional ingredient comprising at least one of a
sweetening agent, a fluoride ion source, a flavoring agent, an
N-acyl sarcosinate, a dispersing agent, a humectant, and water;
adding a weak acid compound until a final pH range of 6.0 to 8.5 is
achieved; stirring the composition for about 40- to 60-minutes; and
filling the composition in container for use, wherein all
compounding operations occur at ambient temperature.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to, and the benefit of:
U.S. patent application Ser. No. 16/133,359, filed Sep. 17, 2018,
entitled "ALIPHATIC ANIONIC COMPOUNDS AND OXIDATIVE COMPOUNDS WITH
IMPROVED STABILITY AND EFFICACY FOR USE IN PHARMACEUTICAL
COMPOSITIONS"; PCT Application No. PCT/US2018/049302, filed on Sep.
3, 2018, entitled "ALIPHATIC ANIONIC COMPOUNDS WITH IMPROVED
STABILITY AND EFFICACY FOR USE IN PHARMACEUTICAL COMPOSITIONS";
U.S. Provisional Patent Application No. 62/676,170 filed on May 24,
2018 entitled "ALIPHATIC ANIONIC COMPOUNDS AND OXIDATIVE COMPOUNDS
WITH IMPROVED STABILITY AND EFFICACY FOR USE IN PHARMACEUTICAL
COMPOSITIONS"; U.S. Provisional Patent Application No. 62/553,450
filed on Sep. 1, 2017 entitled "ALIPHATIC ANIONIC COMPOUNDS AND
OXIDATIVE COMPOUNDS WITH IMPROVED STABILITY AND EFFICACY FOR USE IN
PHARMACEUTICAL COMPOSITIONS". The contents of each of the foregoing
applications are hereby incorporated by reference for all
purposes.
TECHNICAL FIELD
[0002] The present disclosure relates generally to a
multi-component composition comprising a combination of an
aliphatic anionic compound and an oxidative compound.
BACKGROUND
[0003] Oxidative compounds interact with various cellular
components, causing, for example, peroxidation and disruption of
membrane layers, oxidation of oxygen scavengers and thiol groups,
enzyme inhibition, oxidation of nucleosides, impaired energy
production, and/or disruption of protein synthesis and, possibly,
cell death. Biomolecules produced by cells and various other
chemical compounds also may be oxidized by the oxidative
compounds.
[0004] Different compounds tend to interact with cellular
components differently, producing differing biological results. For
example, hydrogen peroxide may be more effective in controlling
Pseudomonas aeruginosa and Stenotrophomonas maltophilia than
peracetic acid (PAA). Similarly PAA may be more effective than
chlorine dioxide (ClO.sub.2) at preventing growth of Escherichia
coli, Listeria monocytogenes, and Salmonella typhimurium. The
biocidal activity of one oxidative compound or composition cannot
readily predict the biocidal activity of another oxidative compound
or composition.
[0005] Nonetheless, it may be desirable to add certain oxidative
compounds to certain drug products and other therapeutic
preparations, including prescription and over-the-counter products
and preparations, including cosmetic preparations. Formulating and
manufacturing such a product or preparation can be difficult
however because of the reactivity of such oxidizing compounds,
particularly at the required pH range and selecting other
ingredients for such products or preparations. Among others,
oxidative compounds may react chemically, such as with the hydroxy
groups of alcohols and polyhydroxy compounds. For example, chlorine
dioxide in aqueous solution with the desired pH range from about
6.0 to about 8.0 decomposes to the chlorite and chlorate ions.
Sodium chlorite is a common source of chlorine dioxide. This may
lead to degradation of the oxidative compounds, the active
ingredient(s), or other excipients in a multi-component
composition. Such degradation may reduce the efficacy or needed
shelf-life of the intended product. Accordingly, various challenges
confront the manufacture of pharmaceutical and cosmetic products
containing oxidative compounds. Thus, the achievement and
maintenance of the stability of oxidizing compounds is an important
and desired characteristic for commercial uses and
applications.
[0006] One such product may be a fluoride toothpaste composition.
Here, it may be desirable to maintain and extend the stability of
the active ingredient(s) (e.g., fluoride ion), and other
excipients, such as flavor, including stabilized chlorine dioxide
or sodium chlorite. Stability may be considered from the time of
manufacture, through distribution and sale, to the time of intended
use.
[0007] The U.S. Pharmacopoeia (USP) defines the stability of a
pharmaceutical product as "extent to which a product retains within
specified limits and throughout its period of storage and use,
i.e., its shelf life, the same properties and characteristics that
it possessed at the time of its manufacture."
http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1191.html (last
visited September 2018).
SUMMARY OF THE INVENTION
[0008] In accordance with various aspects, a multi-component
composition is provided, as well as various formulations of the
multi-component composition, including methods of administration
and methods of use. In one aspect, the multi-component composition
comprises an aliphatic anionic compound and an oxidative compound.
In embodiments, the multi-component composition may comprise N-acyl
sarcosinate and stabilized chlorine dioxide.
[0009] In embodiments, multi-component composition is provided,
comprising: from about 0.01% to about 5.0% of an aliphatic anionic
compound, based on a total weight of the multi-component
composition; from about 0.001 to about 8% of an oxidative compound,
based on a total weight of the multi-component composition; a
buffering system, wherein pH of the multi-component composition is
between 6.0 and 8.0; and water. In further embodiments, the
aliphatic anionic compound facilitates stability of the oxidative
compound. In further embodiments, the aliphatic compound
facilitates efficacy of the composition.
[0010] In further embodiments, the aliphatic anionic compound
comprises, at least one of, N-acyl sarcosinate, taurates, sodium
lauryl sulfoacetate, sodium lauryl isethionate, sodium laureth
carboxylate.
[0011] In further embodiments, the N-acyl sarcosinate is, at least
one of, sodium lauroyl sarcosinate, sodium cocoyl sarcosinate,
sodium myristoyl sarcosinate, sodium oleoyl sarcosinate, or sodium
stearoyl sarcosinate.
[0012] In further embodiments, the oxidative compound comprises, at
least one of, ammonium peroxydisulfate, carbamide (urea) peroxide,
ferric chloride, hydrogen peroxide, potassium bromate, potassium
chlorate, potassium perchlorate, potassium dichromate, potassium
ferricyanide, potassium peroxymonosulfate, potassium persulfate,
sodium bromate, sodium chlorate, sodium perchlorate, sodium
chlorite, sodium hypochlorite, sodium iodate, sodium perborate,
sodium percarbonate, sodium persulfate, stabilized chlorine
dioxide, strontium peroxide, and zinc peroxide.
[0013] In certain aspects, the multi-component composition is
formulated in at least one of a mouth rinse, a gum, a gel, a paste,
a cream, and a lozenge.
[0014] In various embodiments, the multi-component composition
comprises an orally acceptable aqueous vehicle comprising, at least
one, a humectant, an abrasive, a pharmaceutically acceptable
carrier, a fluoride ion source, and a thickening agent.
[0015] In further embodiments, the multi-component composition
oxidizes salivary biomolecules.
[0016] In further embodiments, the multi-component composition
oxidizes salivary biomolecules in 30 to 120 seconds of contact with
saliva.
[0017] In some embodiments, the salivary biomolecules are pyruvate
and L-methionine.
[0018] In further embodiments, the multi-component composition is
applied to, at least one of, anal, aural, nasal, oral, and
urogenital cavities.
[0019] In further embodiments, less than 20% of the oxidative
compound is destabilized after 3 months at 40.+-.1.degree. C. and
70-75% relative humidity or one year under ambient conditions.
[0020] In further embodiments, the oxidative compound is stabilized
chlorine dioxide, wherein less than 20% of the stabilized chlorine
dioxide is degraded after 3 months at 40.+-.1.degree. C. and 70-75%
relative humidity or one year under ambient conditions.
[0021] In certain aspects, an oral care composition is provided,
comprising: from about 0.01% to about 5.0% of an N-acyl
sarcosinate, based on a total weight of the oral care composition;
from about 0.001 to about 8% of an oxidative compound, based on the
total weight of the oral care composition; a buffering system,
wherein pH of the multi-component composition is between 6.0 and
8.0; and water, wherein the N-acyl sarcosinate provides enhanced
stability and efficacy for the oxidative compound in the oral care
composition.
[0022] In further embodiments, the oral care composition further
comprises, at least one of, a humectant, a whitening agent, a
thickening agent, a fluoride ion source, a sweetening agent, an
abrasive, a flavoring agent, a coloring agent, and a gelling
agent.
[0023] In further embodiments, the oral care composition is a
dentifrice.
[0024] In further embodiments, less than 20% of the oxidative
compound is degraded in 3 months at 40.+-.1.degree. C. and 70-75%
relative humidity or one year under ambient conditions.
[0025] In some embodiments, the buffering system comprises disodium
hydrogen phosphate and sodium dihydrogen phosphate.
[0026] In further embodiments, the oral care composition decreases
regrowth of an oral polymicrobial biofilm.
[0027] In further embodiments, the oral care composition
effectively reduces regrowth of the oral polymicrobial biofilm in
24 hours.
[0028] In further embodiments, the oral care composition enhances
remineralization of tooth enamel.
[0029] In further embodiments, the oral care composition oxidizes
salivary biomolecules such as pyruvate and L-methionine in 30 to 60
seconds of contact with the saliva in the oral cavity.
[0030] In further embodiments, the oral care composition provides
an increased amount of available chlorite ion.
[0031] In some aspects, a method for enhancing fluoride uptake into
an oral cavity is provided, comprising: preparing an oral care
composition comprising from about 0.01% to about 5.0% of an N-acyl
sarcosinate, based on a total weight of the oral care composition,
from about 0.001 to about 8% of an oxidative compound, based on the
total weight of the oral care composition, a buffering system,
wherein pH of the multi-component composition is between 6.0 and
8.0, water; and applying the oral care composition to the oral
cavity.
[0032] In further embodiments, the enhanced fluoride uptake into
the oral cavity is increased by at least 2-fold.
[0033] In further embodiments, the enhanced fluoride uptake into
the oral cavity is increased by at least 4-fold.
[0034] In further embodiments, the oral care composition enhances
fluoride uptake.
[0035] In certain aspects, a method to decrease regrowth of oral
polymicrobial biofilm is provided, comprising: preparing an oral
care composition comprising from about 0.01% to about 5.0% of an
N-acyl sarcosinate, based on a total weight of the oral care
composition, from about 0.001 to about 8% of an oxidative compound,
based on the total weight of the oral care composition, a buffering
system, wherein pH of the multi-component composition is between
6.0 and 8.0, water; and applying the oral care composition to an
oral cavity.
[0036] In further embodiments, the oral care composition decreases
regrowth of oral polymicrobial biofilm.
[0037] The contents of this section are intended as a simplified
introduction to the disclosure, and are not intended to limit the
scope of any claim.
BRIEF DESCRIPTION OF THE DRAWING FIGURES
[0038] FIG. 1 is a graph illustrating fluoride uptake of commercial
products and an oral care composition according to an
embodiment.
[0039] FIG. 2 is a graph illustrating tooth remineralization of
commercial products to an oral care composition according to an
embodiment.
[0040] FIG. 3 illustrates zero-order electronic absorption spectra
of aqueous extracts of Toothpaste B.
[0041] FIG. 4 illustrates zero-order electronic absorption spectra
of aqueous extracts of Toothpaste C.
DETAILED DESCRIPTION
Definitions
[0042] The following is a list of definitions for terms used
herein. Unless defined otherwise, all technical and scientific
terms used herein generally have the same meaning as commonly
understood by one of ordinary skill in the art. In the event that
there is a plurality of definitions for a term herein, those in
this section prevail unless stated otherwise. Generally, the
nomenclature used herein and the laboratory procedures in
cytopathicity analysis, microbial analysis, organic, physical and
inorganic chemistry, and dental clinical research are those
well-known and commonly employed in the art.
[0043] As used herein, "about" will be understood by persons of
ordinary skill in the art and will vary to some extent on the
context in which it can be used. Generally, "about" encompasses a
range of values that are plus/minus 10% of a reference value,
unless specifically defined. For instance, "about 25%" encompasses
values from 22.5% to 27.5%.
[0044] As used herein, "acid source" means a biological material,
usually a particulate material, or which is itself acidic or
produces an acidic environment when in contact with liquid water or
oxychlorine anion.
[0045] As used herein, "ambient conditions" means approximately
room temperature (e.g., 20-35.degree. C.) and relative humidity of
approximately <70%.
[0046] As used herein, "a reasonable period of time" means the
time, ranging from months to years, depending upon the application,
a composition may be expected to maintain a safe and efficacious
amount of its combined ingredients.
[0047] As used herein, "shelf-life stable" and "shelf-life
stability" are used interchangeably and refer to the
multi-component composition being deemed consumer acceptable after
a defined period of time after its production (under ambient
conditions).
[0048] As used herein, "bioavailability" means to the absorption or
penetration of the active agent(s) of the composition into the
organic matter to which it is exposed and/or the absorption rate
proportion of the dose of the composition that reaches the systemic
circulation of the organic matter for which its use is intend. For
example, when a composition is administered intravenously, its
bioavailability is nearly 100%, while when the composition is
administered topically, a fraction of the total composition reaches
systemic circulation. Some embodiments described herein provide
enhanced penetration or absorption of oxidative compounds when
applied topically to organic matter. The term "bioavailability"
also refers to its availability for efficacy at the desired site
and for efficacy that either intracellular, extracellular or within
biofluids/biological fluids.
[0049] As used herein, "aliphatic anionic compounds" means
aliphatic compounds comprising anionic moiety that exhibit surface
active properties, ionic interactions with other compounds,
physical interaction, etc. as a result of combined physico-chemical
properties of aliphatic and anionic structural moieties.
[0050] As used herein, "oxidative compounds" means compounds
exhibiting oxidation reaction of biomolecules such as organic
acids, amino acids, sulfur compounds, precursors of sulfur
compounds, proteins, enzymes etc.
[0051] As used herein, "biocidal", "bactericidal", "fungicidal" or
synonymous terms means the property of inactivating or killing
microorganisms, such as bacteria, algae, yeast, and fungi. As used
herein, "biocidal" also refers to the effect of a composition as a
treatment for reduction of bacterial or fungal or microbial growth
or overgrowth in fluids or biofilm which may be associated with
alleviating a diseased condition or state.
[0052] As used herein, "biostatic", "bacteriostatic", fungistatic"
or synonymous terms means the property of arresting the growth of
microorganisms, such as bacteria, algae, yeast and fungi. As used
herein, "biostatic" means to the effect of a composition in
maintaining the polymicrobial mixture of a fluid or a biofilm, as
in maintaining the oral ecology so that one or more organisms have
not overgrown to enable inflection and disease. Compositions with
biostatic attributes are useful in health maintenance, wellness and
prevention of infection and disease.
[0053] As used herein, "stabilized chlorine dioxide," means an
aqueous solution comprised of sodium chlorite or chlorite ion
source and a compounds or compounds intended to inhibit or slow the
degradation of the chlorite or chlorite ion source.
[0054] As used herein, a "biofilm" means a biological aggregate
that forms a layer on a surface, the aggregate comprising a
community of microorganisms embedded in an extracellular matrix of
polymers and/or other biocompounds such as glycoproteins.
Typically, a biofilm comprises a diverse community of
microorganisms, including bacteria (aerobic and anaerobic), algae,
protozoa, yeast, and fungi. While monospecies biofilms also exist,
biofilms in vivo become polymicrobial as they develop overtime
creating oxygen-scare environments where anaerobic pathogens thrive
and where the biofilm matrix protects the polymicrobial mixture
within from antimicrobial treatment.
[0055] As used herein, "buffering system" means a system containing
two or more agents characterized as an acid and its conjugate base
or vice versa. Suitable components of buffering system may include
carbonates, borates, phosphates, imidazole, citrates, acetates and
mixtures thereof, and further may include any of monosodium
phosphate, disodium phosphate, trisodium phosphate, alkali metal
carbonate salts, imidazole, pyrophosphate salts, acetic acid,
sodium acetate, citric acid, and sodium citrate. Exemplary
compounds used in generating buffering system are described in more
detail in Kirk & Othmer, Encyclopedia of Chemical Technology,
Fourth Edition, Volume 18, Wiley-Interscience Publishers
(1996).
[0056] As used herein, "pH modifying agent" means an agent capable
of modifying pH. pH modifying agents include acidifying agents to
lower pH, basifying agents to raise pH and buffering agents to
control pH within a desired range. Use or presence of single pH
modifying agent may not result in a buffered composition.
[0057] As used herein "a carrier" means those components of a
composition that are capable of being commingled to provide
required physical consistency and consumer goodness properties
without interaction with other ingredients.
[0058] As used herein, "orally acceptable carrier" means a suitable
vehicle or ingredient, which can be used to form and/or apply the
present compositions to the oral cavity in a safe and effective
manner.
[0059] As used herein, "compatible" means that the components of
the composition are capable of being commingled without interaction
in any manner which would substantially reduce the stability of the
oxidative compounds, ingredients required for the efficacy, the
carrier and excipients, and the consumer qualities of the
composition.
[0060] As used herein, "consumer goodness qualities" include, but
are not limited to, appearance, viscosity, taste, odor,
abrasiveness, color, flavor, and moisturizing attributes of the
compositions deemed desirable by consumers through consumer product
testing or other such means. For example, it may be desirable that
a tube of toothpaste produce a ribbon stripe of toothpaste on a
toothbrush when squeezed and that the toothpaste composition is
neither too firm to be squeezed easily from the tube nor too
viscous so as not to hold or rest on the toothbrush ready or
use.
[0061] As used herein, "dental plaque" means a polymicrobial
biofilm that forms on the surface of teeth.
[0062] As used herein, "dual phase composition" means a composition
wherein certain ingredients are contained in one part and other
ingredients are contained separately in a second part at the time
of manufacture and prior to use to prevent the reactivity of the
oxidative compounds to the carrier and other excipients of the
composition. The bioavailability of dual phase compositions may be
determined once the two phases are mixed at the time of use. A
difference between single phase and dual phase compositions may
include how shelf-life is determined. Because the two phases of a
dual phase compositions are combined just prior to usage, the
shelf-life stability of dual phase compositions is the short period
from the time of mixing just prior to use to the time of use which
may occur immediately thereafter. Dual-phase compositions may not
have the required attribute of maintaining stability of components
from the time of manufacture to the time of usage precisely because
the phases of the composition are not intended to be mixed until
just prior to usage.
[0063] As used herein, "essentially free" means a composition which
is comprised of very low levels, below detection levels of commonly
used analytical methods, of a specific ingredient or compound or
molecule.
[0064] As used herein, "vehicle" means an orally-acceptable
dentifrice vehicle used to prepare a dentifrice composition
comprising a water-phase, containing a humectant therein.
[0065] As used herein, "dentifrice" means paste, gel, powder,
tablets, or liquid formulations, unless otherwise specified, that
are used to clean the surfaces of the oral cavity.
[0066] As used herein, "teeth" refers to natural teeth as well as
artificial teeth or dental prosthesis.
[0067] As used herein, "efficacious amount" means any amount of the
agent that may result in a desired biocidal or biostatic or
chemical or physiological effect, a desired cosmetic effect, and/or
a desired therapeutic biological effect. In one example, an
efficacious amount of an agent used for tooth whitening may be an
amount that may result in whitening of a tooth with one or more
treatments. In another example, an efficacious amount of an agent
used for wound treatment is an amount that may result in a
statistically significant improvement in wound healing.
[0068] As used herein, "film" means a layer of a material having
two dimensions substantially larger than the third dimension. A
film may be a liquid or a solid material. For some materials, a
liquid film can be converted into a solid film by curing, for
instance, by evaporation, heating, drying, cross-linking, adhering,
adduct formation, and like phenomena.
[0069] As used herein, "hard tissue" means any toe and finger nail,
hard keratinized tissue, hard tooth tissue, bone, tooth and the
like, found in animals such as mammals.
[0070] As used herein, "irritating" and "irritation" refer to the
property of causing a local inflammatory response, such as
reddening, swelling, itching, burning, or blistering, by immediate,
prolonged, or repeated contact. For example, inflammation of a
non-oral mucosal or dermal tissue in a mammal can be an indication
of irritation to that tissue. A composition may be deemed
"substantially non-irritating" or "not substantially irritating,"
if the composition is judged to be slightly or not irritating using
any standard method for assessing dermal or mucosal irritation.
[0071] As used herein, "pharmaceutically acceptable" is set forth
broadly and refers without limitation to those compounds,
materials, compositions and/or dosage forms which are, within the
scope of sound medical judgment suitable for contact with the
tissues of and/or for consumption by human beings and animals
without excessive toxicity, irritation, allergic response, or other
problem complications commensurate with a reasonable risk/benefit
ratio.
[0072] As used herein, the abbreviation "ppm" means parts per
million by weight or volume as applicable.
[0073] As used herein, "overgrowth" refers to excessive
concentrations of bacteria, algae, yeast, and/or fungi leading to
inflammation, infection, pathogenesis and disease. Overgrowth may
occur in biofilms and plaques containing polymicrobial mixtures of
bacteria, algae, yeast, and/or fungi, such as those found in the
biofilms associated with mucositis and with dental plaque.
Overgrowths of pathogenic microbes within biofilms are known to
increase significantly their resistance to treatment and increase
the incidence of inflamed tissues, infection and disease.
[0074] As used herein, "prophylactic" means treatment administered
to a subject who does not exhibit signs of a disease or exhibits
early signs of the disease for the purpose of decreasing the risk
of developing pathology associated with the disease.
[0075] As used herein, "range" means the area of variation between
upper and lower limits on a particular scale. It is understood that
any and all whole or partial integers between any ranges set forth
herein are included herein.
[0076] As used herein, "safe and effective amount" and similar
terms mean an amount of an ingredient, such as the amount of an
oxidative compound, in composition of sufficient dosage to
positively modify the condition to be treated, but low enough to be
safe for humans and animals to use without serious side effects (at
a reasonable benefit/risk ratio), within the scope of sound
medical/dental judgment. "Safe and effective" pertains not only to
the dosage amount but also the dosage rate (rate of release) of the
oxidative compound applied in treatment. The safe and effective
amount of oxidative compound in a composition may vary with the
particular condition being treated, the age and physical condition
of the patient being treated, the severity of the condition, the
duration of treatment, the nature of concurrent therapy, the
specific form (e.g., salt) of the oxidative compound employed, and
the particular vehicle from which the oxidative compound is
applied.
[0077] As used herein, a "single phase composition" means a
composition wherein all ingredients are composed in a single
container at the time of composing and are not mixed with other
ingredients subsequently. Thus, single phase compositions are ready
for use at any time during their shelf-life without further
preparation or mixing. The bioavailability of single phase
compositions may be determined at any point during their useful
shelf-life.
[0078] As used herein, "stability" means the prevention of a
reaction, reduction or degradation of components, such as of
oxidative compounds, comprised in a multi-component composition. A
multi-component composition may be "stable" if the oxidative
compounds of the multi-component composition are not reactive with
each other for a reasonable period of time. For example, a
multi-component composition may stable if it maintains consumer
qualities and exhibits less than 35% loss of the oxidative
compounds for a period of 24 months at about 25.degree. C. (ambient
temperature) or 6 months at an accelerated temperature of
40.degree..+-.2.degree. C. and 75%.+-.5% Relative Humidity
(RH).
[0079] As used herein, "shelf-life" means the length of time
compositions maintain the desired stability of the oxidative
compounds and the consumer qualities of the composition. For
example, a target or stable shelf life for a composition may not
comprise more than 35% loss in the concentration of oxidative
compound in 6 months at 40.+-.2.degree. C. and 75%.+-.5% RH, which
is equivalent to 2 years of shelf life at room temperature.
[0080] As used herein, "therapeutic" means intended to be
administered to a subject who exhibits signs of pathology for the
purpose of diminishing or eliminating those signs.
[0081] As used herein, "topical composition" means a product which
is not intentionally ingested or otherwise applied without recovery
for purposes of systemic administration of therapeutic agents, but
is retained in the anal, aural, oral, nasal, ocular, or urogenital
cavities or upon the skin or other outer surfaces of the body, or
upon an area of affected soft tissue for a time sufficient to
contact substantially all of the surfaces and/or tissues for
purposes of administration and delivery of therapeutic agents.
[0082] As used herein, "wound" means a laceration, abrasion,
puncture, burn, and/or other injury to any one or more soft and/or
hard tissue. Exemplary tissues considered for such wound treatment
include mucosal tissue and dermal tissue including epidermal
tissue, dermal tissue, and subcutaneous tissue (also called
hypodermis tissue). As used herein, a wound also encompasses a
laceration, a puncture, and/or an avulsion of a fingernail or
toenail. A wound can penetrate the tissue partially or completely.
A wound can arise accidently or intentionally, e.g., a surgical
wound.
[0083] As used herein, "dispersing agent" means a compound that
improves the separation of particles and prevents settling or
clumping of an ingredient(s) in a multicomponent composition.
[0084] As used herein, "emollient agent" means a compound that
reduces the loss of water from a composition.
[0085] As used herein, "suspending or emulsifying agent" means a
compound that achieves uniform dispersion of an ingredient(s) in a
multicomponent composition.
[0086] As used herein, "fragrance" means a compound that provides a
pleasing scent or order similar to perfume to a composition.
[0087] As used herein, "cooling agent" means a compound that
provides a cooling, soothing, or pleasant feeling when a
composition is topically applied to hard and soft tissues.
[0088] As used herein, "warming agent" means a compound that
provide an olfactory sensation, especially warm sensation. Warming
agents are often desired in various cosmetic preparations, such as
shaving creams, hand lotions, body lotions, facial preparations,
including masks, depilatories.
[0089] As used herein, "humectant" means a compound that preserves
moisture in a composition. Some embodiments described herein
include one or more compounds such as cellulose gum,
carboxymethylcellulose, pectin, guar gum, xanthan gum, N-acyl
sarcosinate, sodium lauroyl sarcosinate, sodium cocoyl sarcosinate,
or sodium myristoyl sarcosinate.
[0090] As used herein, "thickener" means a compound that increases
viscosity of a composition.
[0091] As used herein, "excipient" means a compound that provides
physical and consumer goodness properties to a composition for its
acceptance. Examples of such properties (but not limited to) are
viscosity, appearance, flavor, color, thickness, sweetness, gel
like structure, preservative, uniform suspension or combinations
thereof.
[0092] As used herein, the term "abrasive agent" means a compound
that helps to remove coating (or deposits) from hard or soft
tissues, such as that on a tooth surface while brushing using a
composition, such as a toothpaste.
[0093] As used herein, "desensitizing agent" means a compound that
helps reduce or alleviate sensitivity and pain. For example, a
desensitizing agent in a topical resin, varnish, toothpaste or
mouthwash may occlude dentin tubules or may desensitize nerve
fibers, blocking the neural transmission.
[0094] All percentages and ratios used herein are by weight of a
multi-component composition and not of the overall topical
formulation that is delivered, unless otherwise specified. All
measurements are made at room temperature i.e. 20-25.degree. C.,
unless otherwise specified. The concentration of a dissolved
oxidative compound may depend on the temperatures and the range of
humidity to which the solution is likely to be subjected. Heat and
humidity, under normal circumstances, may cause such a composition
to degrade from liquid to gas, changing its weight and rendering
common assay calculations inaccurate.
Detailed Description of the Embodiments
[0095] In aspects, the multi-component composition comprises an
oxidative compound. In embodiments, an oxidizing compound comprises
at least one of a low-molecular-weight compound, a compound of
suitable size and properties to permit diffusion or uptake through
cell wall to react with internal cell components, and a compound
which stimulates apoptotic or necrotic cell death. In further
embodiments, the oxidizing compound includes compounds having a low
oxidizing threshold, indicating that the selected oxidizing
compounds interact strongly with its target by chemical rather than
physical means. In further embodiments, the oxidative compound
comprises, at least one of, chlorine dioxide or a chlorite ion
source, such as stabilized chlorine dioxide, a chlorite salt,
ammonium peroxydisulfate, carbamide (urea) peroxide, ferric
chloride, hydrogen peroxide, potassium bromate, potassium chlorate,
potassium perchlorate, potassium dichromate, potassium
ferricyanide, potassium peroxymonosulfate, potassium persulfate,
sodium bromate, sodium chlorate, sodium perchlorate, sodium
chlorite, sodium hypochlorite, sodium iodate, sodium perborate,
sodium percarbonate, sodium persulfate, strontium peroxide, zinc
acetate, zinc peroxide, zinc chloride or the like.
[0096] In further embodiments, a multi-component composition may
comprise from about 0.005% to about 8.0% oxidative compound, such
as a chlorite ion sources and/or stabilized chlorine dioxide. In
further embodiments, the multi-component composition may include
from about 0.005% to about 4.0% oxidative compound. In further
embodiment, the multi-component composition may include from about
0.005% to about 3.0% oxidative compound.
[0097] In another embodiment, the multi-component composition
includes from about 0.005% to about 2.0% oxidative compound.
[0098] In certain aspects, the multi-component composition
comprises an aliphatic anionic compound. In some embodiments, the
aliphatic anionic compound comprises water-soluble salts having
from about 8 to 20 carbon atoms in an alkyl radical, such as
taurates, sodium lauryl sulfoacetate, sodium lauryl isethionate,
and sodium laureth carboxylate. In some embodiments, the aliphatic
anionic compound comprises an N-acyl sarcosinate compound. N-acyl
sarcosinates may comprise the following general structure: where R
is typically a fatty acid of chain length C.sub.8 to C.sub.20.
N-acyl sarcosinates may include lauroyl sarcosinate, cocoyl
sarcosinate, myristoyl sarcosinate, oleoyl sarcosinate, stearoyl
sarcosinate and other such compounds identifiable to a person
skilled in the art. In embodiments, the aliphatic anionic compound
are provided in the form of a salt or a pharmaceutically accepted
salt, such as, sodium lauroyl sarcosinate, sodium lauryl
sulfoacetate, sodium lauryl isethionate, sodium laureth
carboxylate, sodium cocoyl sarcosinate, and sodium myristoyl
sarcosinate.
[0099] In further embodiments, a multi-component composition is
provided, comprising from about 0.001% to about 20.0% aliphatic
anionic compound. In further embodiments, the multi-component
composition includes from about 0.001% to about 10% of an aliphatic
anionic compound. In further embodiments, the multi-component
composition may include from about 0.001% to about 5.0% of an
aliphatic anionic compound. In further embodiments, the
multi-component composition includes from about 0.001% to 1% of an
aliphatic anionic compound. In further embodiments, the
multi-component composition includes from about 0.01% to 1% of an
aliphatic anionic compound. In further embodiments, the
multi-component composition includes from about 0.01% to 5% of an
aliphatic anionic compound.
[0100] In further embodiments, the multi-component composition
includes from about 0.2% to 5% of an aliphatic anionic compound. In
further embodiments, the multi-component composition includes from
about 0.5% to about 5% of an aliphatic anionic compound.
[0101] In certain aspects, the multi-component composition
comprises a carrier. In embodiments, suitable carrier(s) comprise
those that satisfy various considerations based on compatibility
with the other ingredients required for the efficacy, consumer
qualities, cost, and contribution to shelf stability. In
embodiments, the selected carrier does not substantially reduce
either the stability of the composition or its efficacy. Examples
of suitable carriers variously include gelling agents, whitening
agents, flavoring agents and flavoring systems, coloring agents,
abrasive agents, foaming agents, desensitizing agents, dispersants,
humectants, sweetening agents analgesic and anesthetic agents,
anti-inflammatory agents, anti-malodor agents, anti-microbial
agents, anti-plaque agents, anti-viral agents, biofilm disrupting,
dissipating or inhibiting agents, cellular redox modifiers,
antioxidants, cytokine receptor antagonists, dental anti-calculus
agents, fluoride ion sources, hormones, metalloproteinase
inhibitors, enzymes, immune-stimulatory agents, lipopolysaccharide
complexing agents, tissue growth factors, vitamins and minerals,
water, and mixtures thereof.
[0102] In aspects, the multi-component composition comprises a
buffering system. The buffering system may be required to achieve
and maintain a pH of the multi-component composition in the range
required to prevent the degradation of the oxidative compound in
the multi-component composition. In embodiments, the buffering
system may comprise an acid and its conjugate base or a base and
its conjugate acid. In embodiments, the buffering system may
comprise an organic acid and its conjugate base or an organic base
and its conjugate acid. In some embodiments, the buffering system
may comprise an inorganic acid and its conjugate base or an
inorganic base and its conjugate acid. In embodiments, the
buffering system comprises an organic acid and an inorganic base or
an inorganic acid and an organic base. In embodiments, the
buffering system maintains a composition pH at a range from about
6.0 to about 8.5. A buffering system may also be useful to achieve
consumer goodness properties. A buffering system generally differs
from a single pH modifying agent used to reduce the pH of a
composition or raise the pH of a composition.
[0103] In embodiments, a buffering system comprises from about 0.2%
to about 4.0%, from about 0.05% to about 0.5%, from about 0.2% to
about 2.0%, or from about 0.7% to about 4.2%, or from about 0.7% to
about 2.2% of a base compound. In various embodiments, the
buffering system comprises from about 0.01% to about 4.0%, from
about 0.01% to about 0.10%, from about 0.01% to about 0.05%, from
about 0.01% to about 0.05%, from about 0.04% to about 2.1% or from
about 0.05% to about 2.2%, from about 0.06% to about 0.2%, from
about 0.00% to about 0.1% of an acidic compound.
[0104] In aspects, the multi-component composition includes one or
more pH modifying agents. pH modifying agents for use herein may
include acidifying agents to lower pH, basifying agents to raise
pH. For example, one or more compounds can provide a pH from about
2 to about 10, or from about 2 to about 8, or from about 3 to about
9, or from about 4 to about 8, or from about 5 to about 7, or from
about 6 to about 10, or from about 6 to about 8, or from about 7 to
about 8, or from about 7 to about 9, and any pH above or below this
range or any fractional range in between. Orally acceptable pH
modifying agent including without limitation carboxylic, phosphoric
and sulfonic acids, acid salts (e.g., monosodium citrate, disodium
citrate, monosodium malate, etc.), alkali metal hydroxides such as
sodium hydroxide, carbonates such as sodium carbonate,
bicarbonates, sesquicarbonates, borates, silicates, phosphates
(e.g., monosodium phosphate, trisodium phosphate, pyrophosphate
salts, etc.), imidazole and mixtures thereof. One or more pH
modifying agents are optionally present in a total amount effective
to adjust the composition to an orally acceptable pH range.
[0105] In some embodiments, the multi-component composition may
include from about 0.01% to about 10% pH modifier agents based on a
total weight of the oral care composition. In some embodiments, the
pH modifier agents may be from about 0.01%, 0.1%, 1%, 2%, 3%, 4%,
5%, 6%, 7%, 8%, 9% or to about 10% by weight or volume of the
multi-component composition. In other embodiments, a
pharmaceutically acceptable carrier may be in an amount from about
0.01% to about 5%, from about 0.01% to about 3%, or from about
0.01% to about 2%. Use or presence of single pH modifying agent
generally does not result a buffered composition.
[0106] In some aspects, the multi-component composition may further
comprise one or more additional active ingredients. In some
embodiments, an additional active ingredient may include one or
more of the following additional ingredients: fluoride ion sources,
anti-microbial agents, analgesic compounds, anti-inflammatory
agents, anti-malodor agents, anti-plaque agents, anti-viral agent,
biofilm disrupting, dissipation or inhibiting agents, hormones,
enzymes, metalloproteinase inhibitors, immune-stimulatory agents,
and numbing agents. In further embodiments, the multi-component
composition comprises one or more excipients including any of
water, abrasives, humectants, thickeners, sweeteners, moisturizers,
flavors, colors, fillers, and extenders.
[0107] In some aspects, the multi-component composition comprises a
pharmaceutically acceptable carrier and/or excipients.
Pharmaceutically-acceptable carriers include one or more compatible
solid or liquid materials, including diluents or encapsulating
substances, which are suitable for topical administration to the
human or animal body and provide physical action or
consumer-goodness characteristics acceptable to the user. The
pharmaceutical carriers and/or excipients may be combined with the
oxidative compounds in a single phase multi-component composition
without interaction in any manner that would reduce the stability
of the oxidative compound, the consumer goodness qualities, the
safety and effectiveness of the composition in treating or
preventing anal, aural, oral, nasal, ocular, urogenital, foot, and
skin disorders, or diseases of the skin or foot and the
inflammation and infection of tissues therein. The choice of a
pharmaceutically acceptable carrier and/or excipient may be
determined by the way the composition is to be introduced into the
anal, aural, oral, nasal, ocular, or urogenital cavity, or to be
applied topically in foot care and skin care. The pharmaceutically
acceptable carrier and/or excipient may depend on secondary
considerations such as, but not limited to, consumer goodness
qualities, costs and shelf-life stability.
[0108] In embodiments, the pharmaceutically acceptable carrier
and/or excipients may be in an amount of from about 0.01% to about
30%, for example, from about 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%,
7%, 8%, 9% or to about 10% by weight or volume of the
multi-component composition. In other embodiments, the
pharmaceutically acceptable carrier may be in an amount from about
0.01% to about 60%, from about 0.01% to about 30%, or from about
0.01% to about 20%.
[0109] In aspects, the multi-component composition further
comprises an abrasive agent. Abrasives are useful as carriers of
the multi-component compositions intended for specific oral and
dermal applications and uses. For example, abrasive materials
provide physical abrasion between toothbrush and teeth to clean
pellicle, cuticle, biofilm, plaque, stain, and calculus, while also
contributing to the structure of an embodiment and maintaining
stability of the overall formulation. In certain dermal
embodiments, it may be desirable for the composition to assist in
the exfoliation of skin tissues. In some embodiments, the abrasive
material is selected from a composition that does not excessively
abrade skin, enamel, dentin, or other hard or soft tissues. In
embodiments, the abrasive agent comprises, for example, silicas,
hydrated silicas, including gels and precipitates; insoluble sodium
polymetaphosphate; hydrated alumina; calcium carbonate; calcium
hydrogen orthophosphate dihydrate (known in the trade as "dicalcium
phosphate"); tricalcium phosphate, calcium polymetaphosphate,
sodium bicarbonate and resinous abrasive materials. In some
embodiments, a mixture of abrasives may also be used.
[0110] In embodiments, the abrasive is present in an amount from
about 0.01% to about 70%, for example, from about 0.01%, 0.1%, 1%,
2%, 5%, 10%, 15%, 20%, 30%, 40%, 50% or to about 70% by weight of
the multi-component composition. In some embodiments, the abrasive
agent may be present in an amount from about 6% to about 70%, from
about 10% to about 50%, or from about 6% to about 70%, from about
20% to about 70%. In some embodiments, such as nasal or oral
sprays, oral or vaginal rinses and non-abrasive gel compositions,
such as those used in wound healing, may comprise no abrasive.
[0111] In aspects, the multi-component composition comprises an
alkali metal bicarbonate salt. Alkali metal bicarbonate salts are
soluble in water and, unless stabilized, tend to degrade oxidative
compounds in an aqueous system. Sodium bicarbonate, also known as
baking soda, may be included as an alkali metal bicarbonate salt
into the multi-component composition. In embodiments, the alkali
metal bicarbonate salt is present in an amount of from about 0.01%
to about 70%, for example, from about 0.01%, 0.1%, 1%, 5%, 10%,
20%, 30%, 40%, 50%, 60%, or to about 70% by weight of the
multi-component composition. In some other embodiments, the alkali
metal bicarbonate salt may be in an amount from about 0.5% to about
70%, from about 1% to about 50%, or from about 5% to about 50%.
[0112] In aspects, the multi-component composition further
comprises additional agents which reduce dental plaque, tartar and
calculus from teeth. In embodiments, the additional agents comprise
zinc ions, a cationic material, such as guanides and quaternary
ammonium compounds, as well as non-cationic compounds such as
halogenated salicylanilides. In some embodiments, an anti-calculus
agent is provided, and may be comprised of a pyrophosphate ion
source such as pyrophosphate salts. The pyrophosphate salts may
include in the multi-component composition may include di-alkali
metal pyrophosphate salts, tetra-alkali metal pyrophosphate salts,
and mixtures thereof. Disodium dihydrogen pyrophosphate
(Na.sub.2H.sub.2P.sub.2O.sub.7), tetrasodium pyrophosphate
(Na.sub.4P.sub.2O.sub.7), and tetrapotassium pyrophosphate
(K.sub.4P.sub.2O.sub.7) in their unhydrated as well as hydrated
forms may be used. In embodiments, the pyrophosphate salt may be
present in one of three ways: predominately dissolved,
predominantly undissolved, or a mixture of dissolved and
undissolved pyrophosphate. In embodiments, the multi-component
composition comprises a mixture of dissolved and undissolved
pyrophosphate salts. Polyolefin phosphates include those wherein
the olefin group contains 2 or more carbon atoms. Other useful
materials include synthetic anionic polymers, including
poly-acrylates and copolymers of maleic anhydride or acid and
methyl vinyl ether (e.g., Gantrez.RTM.), as well as, e.g.,
polyamino propane sulfonic acid (AMPS), zinc citrate trihydrate,
poly-phosphates (e.g., tripolyphosphate; hexametaphosphate),
diphosphonates (e.g., EHDP; AHP), polypeptides (such as
polyaspartic and polyglutamic acids), and mixtures thereof.
[0113] In embodiments, the anti-calculus agent may be present in an
amount of from about 0.01% to about 50%, for example, from about
0.01%, 0.1%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, or to about 50%
by weight of the multi-component composition. In other embodiments,
the anti-calculus agent may be present in an amount from about 0.5%
to about 25%, from about 1% to about 25%, or from about 5% to about
50%.
[0114] In aspects, a multi-component composition comprises a
coloring agent. Preferably, the consumer goodness quality of
coloring are not degraded by the oxidative compounds and vice
versa. Coloring enables the consumer to more readily ascertain
usage and dosage. Certain colors of the composition may be deemed
undesirable for certain anal, aural, ocular, oral or urogenital
applications. In embodiments, a coloring agent includes, FD&C
Blue No. 1 or titanium dioxide. Suitable coloring agents include
those that are stable and do not degrade in the presence of the
oxidative compounds and do not degrade oxidative compounds. In
embodiments, the coloring agent may be in an amount of from about
0.01% to about 10%, for example, from about 0.01%, 0.1%, 1%, 2%,
3%, 4%, 5%, 6%, 7%, 8%, or to about 10% by weight or volume of the
multi-component composition. In other embodiments, the coloring
agent may be in an amount from about 0.5% to about 10%, from about
1% to about 10%, or from about 0.01% to about 2%, or from 0.8% to
about 1.1%.
[0115] In aspects, a multi-component composition comprises a
cooling and/or warming agent. Suitable cooling and/or warming
agents may be those that are stable and do not degrade the presence
of the oxidative compound within the compositions, such as those
described in U.S. 2017/0877199 to Patton.
[0116] In aspects, the multi-component composition further
comprises a flavoring agent and/or flavoring systems. Suitable
flavoring agents include those that are stable and do not degrade
in the presence of the oxidative compounds and do not degrade
oxidative compounds. Suitable flavoring systems may include an
emulsified flavoring agent for protecting the flavoring agent from
degradation. Suitable flavoring systems include those that are
taught by U.S. 2012/0164084. In some embodiments, a flavoring agent
comprises menthol, mint oil, emulsified mint oil, bubblegum flavor,
watermelon flavor or different types of berry flavor. In
embodiments, the flavoring agent may be present in an amount of
from about 0.01% to about 10%, for example, from about 0.01%, 0.1%,
1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, or to about 10% by weight or volume
of the multi-component composition. In some other embodiments, the
flavoring agent may be in an amount from about 0.25% to about 1.2%,
from about 1.1% to about 10%, or from about 1.1% to about 7.5%.
[0117] In aspects, the multi-component composition comprises a
sweetening agent. Suitable sweetening agent may be stable and not
degrade in the presence of oxidative compounds or degrade oxidative
compounds. In embodiments, the sweetening agent comprises sucrose,
aspartame, acesulfame, stevia, saccharin; saccharin salts,
especially sodium saccharin; sucralose, sodium cyclamate, and
mixtures thereof. In some embodiments, sweetening agents that are
polyhydroxy alcohols such as xylitol, mannitol, and sorbitol. In
embodiments, a multi-component composition is free of polyhydroxy
sweeteners such as xylitol, mannitol, and sorbitol. In embodiments,
a sweetening agent comprises sucrose, sucralose, acesulfame,
aspartame, cyclamate, or saccharin. In some embodiments, the
sweetener may be in an amount of from about 0.01% to about 0.5%,
for example, from about 0.01%, 0.02%, 0.05%, 0.1%, 0.2%, 0.3%,
0.4%, or to about 0.5% by weight or volume of the multi-component
composition. In some other embodiments, the sweetener may be in an
amount from about 0.05% to about 0.5%, from about 0.1% to about
0.2%, from about 0.01% to about 0.5%, or from 0.01% to about
0.2%.
[0118] In aspects, a multi-component composition further comprises
one or more humectants. Suitable humectants include those that
include at least one of the following: serves to keep pastes and
gels and suspensions from hardening or losing their consumer
goodness qualities when exposed to air, to add to the compositions
a moist feel to the consumer goodness qualities and, for particular
humectants orally applied, to impart desirable sweetness of flavor,
such as toothpaste compositions. In embodiments, the humectant
comprises polyhydroxy alcohols, including arabitol, erythritol,
glycerol, maltitol, mannitol, sorbitol, and/or xylitol. Polyhydroxy
alcohols are commonly accepted excipients and most belong to the
Generally Recognized as Safe (GRAS) category for pharmaceutical,
cosmetic, and food products. Other compounds which provide moist
texture for suitable formulations may also be used. Though
humectants such as glycerol, sorbitol and other polyhydroxy
compounds have been known to cause degradation of oxidative
compounds when comprised in the same single phase, in accordance
with various aspects, it has been discovered that a single phase
multi-component composition comprising the combination of an
oxidative compound and an aliphatic anionic compound (e.g., an
N-acyl sarcosinate compound) that exhibit humectant type in terms
of providing consistency to the composition and surface active
properties may not experience significant degradation of the
oxidative compound. In various embodiments, sorbitol may be a
humectant comprised in the multi-component composition.
[0119] In some embodiments, the humectant may be present in an
amount of from about 0.001% to about 70%, for example, from about
0.001%, 0.01%, 1%, 2%, 5%, 10%, 20%, 30%, 40%, 50%, or to about 70%
by weight or volume of the multi-component composition. In some
other embodiments, the humectant may be in an amount from about 1%
to about 15%, from about 15% to about 55%, or from about 25% to
about 55%.
[0120] In aspects, the multi-component composition comprises a
fluoride ion source. In embodiments, the multi-component
composition includes free fluoride ions or covalently bound
fluorine in a form that may be hydrolyzed by oral enzymes to yield
free fluoride ions. Free fluoride ions comprise sodium fluoride,
silver diamine fluoride, stannous fluoride, or indium fluoride.
Covalently bound fluorine, which can be enzymatically hydrolyzed to
yield free fluoride, may be provided by sodium monofluorophosphate.
In various embodiments, sodium fluoride may be comprised in the
multi-component composition as the source of free fluoride ions. If
a fluoride ion source is used as a component in a multi-component
composition, a "fluoride ion source" as disclosed in, U.S. Pat.
Appl. No. 2011/0318282 may be preferred. In embodiments, it has
been surprisingly found that the presence of a fluoride ion source
in a single phase multi-component composition, comprising for
example the combination of an oxidative compound and an aliphatic
anionic compound (e.g., an N-acyl sarcosinate compound), such
composition may resist significant degradation of the oxidative
compound and promote shelf-life and shelf-stability. In
embodiments, a multi-component composition comprises a fluoride ion
source, an aliphatic anionic compound (e.g., an N-acyl sarcosinate
compound), and an oxidative compound. The composition may remain
stable for a reasonable period of time. The composition may
maintain the capacity for the oxidative compounds of the
composition to react or activate upon use. The composition may
enhance the capacity for the oxidative compounds to increase
penetration of bacteria and biofilms as opposed to comparable
compositions not containing an aliphatic anionic compound. In some
embodiments, the fluoride ion source comprises at least one of an
indium fluoride, sodium fluoride, silver diamine fluoride, stannous
fluoride, or sodium monofluorophosphate.
[0121] In embodiments, a multi-component composition further
comprises a source of fluoride ion providing fluoride ions from
about 0 ppm to about 5000 ppm, or from about 50 ppm to about 3500
ppm, from about 500 ppm to about 3500 ppm. In some embodiments, the
fluoride ion source may be in an amount of from about 0% to about
2.0%, for example, from about 0.01%, 0.1%, 0.15%, 0.2%, 0.3%, 0.4%,
0.5%, 0.6%, 0.7%, 0.8%, or to about 2.0% by weight or volume of the
multi-component composition. In other embodiments, the fluoride ion
source may be in an amount from about 0.0% to about 0.03%, from
about 0.0% to about 0.7%, from about 0.1% to about 0.8%, from about
0.01% to about 0.07%, or from about 0.0% to about 0.8%. A
composition is referred as fluoride-free when the source of
fluoride ion source is 0% or when the composition is essentially
free of fluoride as described herein.
[0122] In aspects, a multi-component composition further comprises
a thickening or binding agent. The thickening or binding agent may
provide desired consumer goodness qualities appropriate to the
multi-component composition, such as the desirable consistency or
viscosity of the composition, to provide desirable dosage and at a
rate of release desired of the oxidative compounds upon use, and to
adhere to hard or soft tissues in a topical application. Examples
of thickening or binding agents include carboxyvinyl polymers,
seaweed derivatives such as carrageenan, hydroxyethyl cellulose,
laponite, powdered polyethylene, and water soluble salts of
cellulose ethers such as sodium carboxymethylcellulose and sodium
carboxymethyl hydroxyethyl cellulose. Natural gums such as gum
karaya, guar gum, xanthan gum, gum arabic, and gum tragacanth can
also be used. Colloidal magnesium aluminum silicate or finely
divided silica may be used as part of the thickening or binding
agent to further improves texture. Higher concentrations of
thickening agents can be used for chewing gums, lozenges (including
breath mints), sachets, non-abrasive gels and gels intended for use
in wound-healing, vaginal or oral disease.
[0123] In some embodiments, the thickening or binding agent may be
present in an amount of from about 0% to about 15%, for example,
from about 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, or to about
15% by weight or volume of the multi-component composition. In some
other embodiments, the thickening or binding agent may be in an
amount from about 0.1% to about 15%, from about 2.0% to about 10%,
from about 4% to about 8%, from about 1.0% to about 4.0%, or from
about 5.0% to about 7.0%.
[0124] In aspects, the multi-component composition further
comprises a whitening and/or opacifying agent. In embodiments, the
whitening and/or opacifying agent comprises a non-hydrogen peroxide
whitening agent. For example, titanium dioxide may be included to a
multi-component composition to achieve whiteness or opaqueness of
the multi-component composition. In various embodiments, a
whitening and/or opacifying agent comprises a peroxide, metal
chlorite, perborate, percarbonate, peroxyacid, persulfate, and
combinations thereof. Suitable peroxide compounds include hydrogen
peroxide, urea peroxide (carbamide peroxide), calcium peroxide, and
mixtures thereof. In various embodiments, the multi-component
composition may be essentially free of glycerin and/or polyhydroxy
compounds. In embodiments, the whitening and/or opacifying agent
may be present in an amount of from about 0% to about 20%, for
example, from about 0.01%, 0.1%, 2%, 4%, 6%, 8%, 10%, 12%, 14%,
16%, or to about 20% by weight or volume of the multi-component
composition. In some other embodiments, the fluoride ion source may
be in an amount from about 0.01% to about 20%, from about 0.5% to
about 10%, or from about 4% to about 7%.
[0125] In aspects, the multi-component composition further
comprises water. Water may provide the remaining weight percent of
the multi-component compositions (i.e., the weight percent not
attributed to the other components described herein). Water
employed in the multi-component compositions used as commercially
suitable topical compositions can be of low ion content and
essentially free of organic impurities. Water can comprise up to
about 98% of the composition, particularly for mouthwashes, mouth
rinses and mouthwashes, oral and nasal sprays, vaginal douches, and
soaks, and preferably from about 5% to about 60%, by weight of the
aqueous compositions herein. These amounts of water include the
free water which is added to the composition plus that which is
introduced with other materials added to the composition. Some
embodiments described herein the multi-compound composition include
powders, lozenges and chewing gum, are of course substantially dry
or contain only a small amount of water.
[0126] In aspects, the multi-component composition further
comprises a surfactant. Surfactants may be anionic, cationic,
non-ionic, or amphoteric (zwitterionic). These may be useful as
foaming agents in oral care, cosmetic, healthcare, and
pharmaceutical products. Such foaming agents may also useful in the
retention of sanitizing and moisturizing agents in skin care
products, such as shaving creams and foams. In embodiments, the
surfactant may be in an amount of from about 0% to about 15%, for
example, from about 0.01%, 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, or
to about 15% by weight or volume of the multi-component
composition. In some other embodiments, the surfactant may be in an
amount from about 0.1% to about 15%, from about 2.0% to about 10%,
or from about 4% to about 8%.
[0127] In aspects, the multi-component composition further
comprises a desensitizing agent. The desensitizing agent may be
provided for temporary relief from pain to hard or soft tissues. In
embodiments, the desensitizing agent comprises compounds such as
strontium chloride, strontium acetate, arginine, hydroxyapatite,
nano-hydroxyapatite (nano-HAp), calcium sodium phosphosilicate,
potassium chloride or potassium nitrate. In various embodiments,
the compositions may be essentially free of compounds, such as
sodium lauryl sulfate, that irritate sensitive body cavities such
as anal, nasal, ocular, oral, and urogenital. Examples of
sensitivities and resultant diseases oral cavity include canker
sores, oral mucositis, and dry mouth.
[0128] In aspects, the multi-component composition further
comprises a preservative. In embodiments, the preservative
comprises a methyl paraben, propyl paraben, disodium EDTA, benzyl
alcohol, benzoic acid, or sodium benzoate. In embodiments, the
preservative may be present in an amount of from about 0% to about
2%, for example, 0.01%, 0.1%, 1%, or 2% by weight or volume of the
multi-component composition. In other embodiments, the surfactant
may be in an amount from about 0.1% to about 0.15%, from about 0.2%
to about 1%, from about 0.01% to 0.5%, or from about 0.4% to about
0.8%.
[0129] In embodiments, the multi-component composition does not
contain a polyhydroxy compound. Polyhydroxy compounds are known to
react and degrade oxidative compounds and compounds, such as
stabilized chlorine dioxide, and therefore, may be excluded from
the multi-component composition. Polyhydroxy compounds may include
glycerin, alcohols, polyethylene glycols, xylitol, and
sorbitol.
[0130] In embodiments, the multi-component compositions described
herein are single-phase composition. In embodiments, the
multi-component composition is configured to form a dentifrice. In
embodiments, the multi-component composition is configured to form
an oral rinse. In embodiments, the multi-component composition is
an oral care composition, such as an oral spray, oral gel, denture
or dental appliance soak, toothbrush soak, or a solution intended
for use in an oral irrigation device.
[0131] In aspects, the multi-component composition is formulated as
a cosmetic. Cosmetic compositions (for example, a solid cosmetic
composition, such as a gel, soft-solid or semi-solid (cream), or
stick), may be comprised of a base composition containing at least
one silicone fluid (for example, silicone liquids such as silicone
oils) which is thickened using a siloxane-based polyamide as a
gelling agent; a carrier in which cosmetically active materials are
incorporated; and at least one active ingredient to provide the
activity for such cosmetic composition. In embodiments, the
cosmetic compositions are transparent (clear), including solid
transparent (clear) compositions. In embodiments, the cosmetic
composition is formulated that the final composition is opaque. In
embodiments, the cosmetic composition is formulated so that the
final composition is not-transparent.
[0132] In embodiments, the cosmetic may further comprise one or
more additional agents as carriers, selected from one or more of
abrasive polishing materials, alkali metal bicarbonate salts,
analgesic and anesthetic agents, anti-inflammatory agents,
anti-malodor agents, anti-microbial agents, anti-plaque agents, and
anti-viral agents, biofilm disrupting, dissipating or inhibiting
agents, buffers and buffering systems, cellular redox modifiers and
antioxidants, coloring agents and coloring systems, cytokine
receptor antagonists, dental anti-calculus agents, hormones,
metalloproteinase inhibitors, immune-stimulatory agents,
lipopolysaccharide complexing agents, tissue growth factors,
titanium dioxide, vitamins and minerals, and mixtures thereof. It
is recognized that in certain forms, such as combinations of
therapeutic agents in the same delivery system, may be useful to
obtain an optimal effect. In some embodiments, the multi-component
composition may be combined with one or more such agents in a
single phase delivery system to provide combined effectiveness,
while maintaining the stability of the oxidative compound (e.g.,
stabilized chlorine dioxide).
[0133] In embodiments, the multi-component composition may be
specifically formulated for use in humans and animals, for example
in the form of rinses, gels, pastes, creams, washes, sprays,
lozenges, therapeutic floss, tape, patches, compresses, or strips,
for use in skin care, oral care, urogenital care, foot care, wound
healing and as a solution used in irrigation devices for use in the
oral and other body cavities.
[0134] In aspects, the multi-component composition has consumer
goodness qualities. In embodiments, ingredients are selected for an
oral care composition that achieves a desirable range of viscosity
to ensure product manufacturability, applicability, stability, and
quality, as well as consumer acceptance. In embodiments, the
multi-component composition may be phase stabile. Phase stability
may refer to an oral care composition visually (i.e., to the
unaided eye) having no liquid separation from the composition's
body over a defined period of time under ambient conditions. Such
phase stable multi-component compositions may resist syneresis. For
example, a toothpaste embodiment herein may be less abrasive on
teeth than a similar composition without the inclusion of aliphatic
anionic compounds. In a liquid embodiment, such as an oral rinse,
consumer goodness qualities may comprise where the composition
retains clarity (clear, water-like appearance); however clarity is
not limited by the presence of a color in the composition if a
color is intended. In another embodiment, a vaginal douche
embodiment should not sting, stain, burn or otherwise cause
irritation to the user, has a viscosity that enables ease of use,
and has a pleasing fragrance or no fragrance at all following use.
Consumer goodness qualities of various embodiments herein may vary
for use with other animals. For example, an oral rinse for dogs may
have preferably a meat flavor while one for humans may have a mint
flavor.
[0135] In aspects, the multi-component composition is suitable for
a variety of indications, including treatment and prevention of
oral or vaginal malodor, as well as ocular, nasal and skin care and
other topical uses. Suitable topical indications include anal,
aural, oral, nasal, ocular, urogenital, foot-care and skin-care
conditions and diseases. The composition may be suitable for select
indications, including antimicrobial, antiseptic, antioxidant,
bactericidal and bacteriostatic, biofilm penetration, biofilm
dissipation and reduction, coagulant, deodorant, desensitizing,
disinfectant, fungicidal and fungistatic, herbicidal, tissue damage
reduction, bleaching, stain removal, and tooth whitening.
Compositions herein are suitable for use in a variety of forms,
including rinses, gels, pastes, creams, washes, sprays, lozenges,
floss, tape, patches, bandages, compresses, wraps, and strips.
[0136] In aspects, the multi-component composition maintains
stability and consumer goodness. In embodiments, stability and
consumer goodness is maintained from manufacture of the composition
through about twelve (12) months of storage under ambient
conditions. In embodiments, the multi-component composition may
exhibit no more than 10% loss in stabilized chlorine dioxide in
three (3) months at 40.+-.2.degree. C. and 75%.+-.5% relative
humidity (RH) which may be equivalent to twelve (12) months of
storage at room temperature. In embodiments, the multi-component
composition may exhibit no more than 20% loss in stabilized
chlorine dioxide in in three (3) months at 40.+-.2.degree. C. and
75%.+-.5% relative humidity (RH). In embodiments, the
multi-component composition may exhibit no more than 30% loss in
stabilized chlorine dioxide in three (3) months at 40.+-.2.degree.
C. and 75%.+-.5% relative humidity (RH). In some embodiments, the
multi-component composition may exhibit no more than 40% loss in
stabilized chlorine dioxide in three (3) months at 40.+-.2.degree.
C. and 75%.+-.5% relative humidity (RH) In another embodiment,
storage of the composition under accelerated conditions (typically
40.+-.2.degree. C. and 75%.+-.5% relative humidity, RH) can project
real time suitability of a composition for consumer use,
anticipating the time of manufacture, transit from point of
manufacture to wholesaler, from wholesaler to retailer, from
retailer to consumer, plus the anticipated storage time by the
consumer as the product is consumed.
Exemplary Composition I: Toothpaste Embodiment
[0137] Various single-phase oral care toothpaste compositions may
comprise: from about 0.005% to about 2.0% a chlorite ion source
such as sodium chlorite, from about 0.7% to about 4.2% a base such
as disodium hydrogen phosphate or trisodium phosphate, from about
0.05% to about 2.20% an acid or a buffering salt on the acidic
side, such as sodium dihydrogen phosphate, citric acid, or acetic
acid, from about 0.2% to about 5.0% an N-acyl sarcosinate compound,
such as sodium lauroyl sarcosinate, sodium cocoyl sarcosinate, or
sodium myristoyl sarcosinate, from about 0.8% to about 1.1%
coloring agent such as FD&C Blue No. 1 or titanium dioxide,
from about 1.0% to about 4.0% gelling agent such as gelatin,
pectin, guar gum, xanthan gum, other natural or synthesized gums,
cellulose gum or sodium carboxymethyl cellulose, from about 20.0%
to about 70.0% abrasive agent such as hydrated silica, calcium
hydrogen phosphate, alumina, sodium bicarbonate, from about 0.05%
to about 0.5% sweetening agent such as sucrose, sucralose,
acesulfame, aspartame, cyclamate, or saccharin, from about 0.025%
to about 1.2% flavoring agent such as menthol, mint oil, emulsified
mint oil, tropical fruit, watermelon, bubblegum, strawberry or
berry flavor, from about 0.0% to about 0.8% fluoride ion source or
source of releasable fluoride ion, such as sodium fluoride, silver
diamine fluoride, sodium monofluorophosphate, or stannous fluoride,
and water to 100%, thereby maintaining the final pH in the range of
about 6.0 to about 8.0. For preparing fluoride-free toothpaste
compositions, the fluoride ion source is eliminated from the
composition and the quantity of water is adjusted accordingly.
Exemplary Composition II: Oral Care Gel Embodiment
[0138] Various single-phase oral care gel compositions may
comprise: from about 0.005% to about 2.0% chlorite ion source such
as sodium chlorite, from about 0.7% to about 4.2% a base, such as
disodium hydrogen phosphate or trisodium phosphate, from about
0.05% to about 2.20% an acid or a buffering salt on the acidic
side, such as phosphoric acid, sodium dihydrogen phosphate, citric
acid, or acetic acid, from about 0.2% to 5.0% an N-acyl sarcosinate
compound, such as sodium lauroyl sarcosinate, sodium cocoyl
sarcosinate, or sodium myristoyl sarcosinate, from about 5.0% to
about 7.0% gelling agent such as gelatin, pectin, xanthan gum, guar
gum, cellulose gum, other natural or synthesized gums, or sodium
carboxymethyl cellulose, from about 0.05% to about 0.5% sweetening
agent such as sucrose, acesulfame, aspartame, sucralose, or
saccharin, from about 0.025% to about 1.2% flavoring agent such as
menthol, mint oil, emulsified mint oil, bubblegum flavor,
strawberry, fruity, watermelon or berry flavor, from about 0.01% to
about 0.8% fluoride ion source such as sodium fluoride stannous
fluoride, or sodium monofluorophosphate, and water to 100% thereby
maintaining the final pH in the range of about 6.0 to about 8.0.
For preparing fluoride-free gel compositions, the fluoride ion
source is eliminated from the composition and the quantity of water
is adjusted accordingly. The composition may comprise a buffering
system and/or a flavoring system as described herein.
Exemplary Composition III: Oral Rinse Embodiment
[0139] Various single-phase oral care rinse compositions may
comprise: from about 0.005% to about 2.0% of chlorite ion source
such as sodium chlorite, from about 0.2% to about 4.0% a base, such
as disodium hydrogen phosphate or trisodium phosphate, from about
0.04% to about 2.10% an acid or a buffering salt on the acidic
side, such as sodium dihydrogen phosphate, phosphoric acid, citric
acid or acetic acid, from about 0.01% to about 1.0% an N-acyl
sarcosinate compound such as sodium lauroyl sarcosinate, sodium
cocoyl sarcosinate, or sodium myristoyl sarcosinate, from about
0.01% to about 0.2% sweetening agent such as sucrose, acesulfame,
aspartame, cyclamate, sucralose, or saccharin, from about 0.025% to
about 1.2% flavoring agent such as menthol, mint oil, emulsified
mint oil, tropical fruit, bubblegum, watermelon, strawberry or
berry flavor, from about 0.0% to about 0.07% fluoride ion source or
source of releasable fluoride ion, such as sodium fluoride,
stannous fluoride, sodium monofluorophosphate, or acidulated
phosphate fluoride, and water to 100% thereby maintaining the final
pH in the range of about 6.0 to about 8.0. For preparing
fluoride-free oral rinse compositions, the fluoride ion source is
eliminated from the composition and the quantity of water is
adjusted accordingly. Similarly, for preparing fluoride-free and
unflavored oral rinse compositions, the fluoride ion source and the
flavoring agents are eliminated from the composition. The
composition may comprise a buffering system and/or a flavoring
system as described herein.
Exemplary Composition IV: Oral Spray Embodiment
[0140] Various oral care spray formulation may comprise: from about
0.005% to about 2.0% chlorite ion source such as sodium chlorite,
from about 0.05% to about 0.5% a base such as disodium hydrogen
phosphate, sodium citrate, or trisodium phosphate, from about 0.01%
to about 0.05% an acid or a buffering salt on the acidic side, such
as phosphoric acid, citric acid, acetic acid, or sodium dihydrogen
phosphate, from about 0.01% to about 1.0% an N-acyl sarcosinate
compound such as sodium lauroyl sarcosinate, sodium cocoyl
sarcosinate, or sodium myristoyl sarcosinate, from about 0.01% to
about 0.5% sweetening agent such as sucrose, acesulfame, aspartame,
cyclamate, sucralose, or saccharin, from about 1.1% to about 7.5%
flavoring agent such as menthol, mint oil, emulsified mint oil,
watermelon, bubblegum, tropical fruit, strawberry or berry flavor,
from about 0.5% to 7.0% dispersing agent such as a polysorbate,
from 0.01% to 0.5% preservative, such as methyl paraben, propyl
paraben, disodium EDTA, sodium benzoate, or combination thereof and
water to 100% thereby maintaining the final pH in the range of
about 6.0 to about 8.0. The composition may comprise a buffering
system and/or a flavoring system as described herein.
Exemplary Composition V: Wound-Healing Gel/Ointment Embodiment
[0141] Various single-phase oral care gel compositions may
comprise: from about 0.005% to about 2.0% chlorite ion source such
as sodium chlorite, from about 0.7% to about 2.2% a base such as
disodium hydrogen phosphate or trisodium phosphate, from about
0.06% to about 0.20% an acid or a buffering salt on the acidic
side, such as sodium dihydrogen phosphate, citric acid, or acetic
acid, from about 0.5 to 5.0% an N-acyl sarcosinate compound, such
as sodium lauroyl sarcosinate, sodium cocoyl sarcosinate, or sodium
myristoyl sarcosinate, from about 5.0% to about 7.0% gelling agent
such as gelatin, pectin, guar gum, xanthan gum, cellulose gum, or
sodium carboxymethyl cellulose, from about 0.025% to about 1.2% a
cooling agent, such as menthol or emulsified mint oil, from about
0.1% to about 10% an emollient agent, such as mineral oil, from
about 0.1% to about 5% a suspending or emulsifying agent, such as a
polysorbate, and water to 100% thereby maintaining the final pH in
the range of about 6.0 to about 8.0. The composition may comprise a
buffering system and/or a flavoring system as described herein.
Exemplary Composition VI: Vaginal Douche Embodiment
[0142] Various single-phase vaginal douche compositions,
preferably, comprise: from about 0.005% to about 2.0% a chlorite
ion source such as sodium chlorite, from about 0.2% to about 2.0% a
base such as sodium bicarbonate, disodium hydrogen phosphate or
trisodium phosphate, from about 0.00% to about 0.10% an acid or a
buffering salt on the acidic side, such as boric acid, citric acid,
acetic acid, or sodium dihydrogen phosphate, from about 0.001% to
about 1.0% an N-acyl sarcosinate compound such as sodium lauroyl
sarcosinate, sodium cocoyl sarcosinate, or sodium myristoyl
sarcosinate, from about 0.1% to about 10% an emollient agent, such
as mineral oil, from about 0.1% to about 5% a suspending or
emulsifying agent, such as a polysorbate or poloxamer, from 0.01%
to 20% a fragrance, such as rose, lilac or geranium fragrance, or
other proprietary fragrance compositions provided by commercial
suppliers of fragrances, and water to 100% thereby maintaining the
final pH in the range of about 6.0 to about 8.0. For preparing
fragrance-free vaginal douche compositions, the fragrance source is
eliminated from the composition and the quantity of water is
adjusted accordingly. The composition may comprise a buffering
system and/or a flavoring system as described herein.
Methods for Preparing Exemplary Compositions
[0143] In preparing compositions as described herein and where the
Exemplary Composition is a paste or gel, the gelling agents are
dissolved in water. Pharmaceutically-acceptable buffering compounds
of the appropriate type and concentration such as weak acid and its
conjugate base or weak base and its conjugate acid are then added
to the solution of gelling agent in water until the preferred final
pH range of 6.0 to 8.5 is achieved. Then the solution containing a
buffering system may be mixed with the chlorite ion source in an
aqueous solution. The remaining ingredients, e.g. humectants,
sweetening agents, coloring agents, abrasive agents, fluoride ion
source, flavoring agent(s), emollient agents, suspending or
emulsifying agents, additional deionized or purified water, and
other ingredients as described above and as applicable, are added
one by one in appropriate amounts to maintain the final pH of the
overall formulation in the range of 6.0 to 8.5. The N-acyl
sarcosinate may be added as a last ingredient while preparing the
composition. All compounding may occur at ambient temperatures to
maintain the stability of the composition.
[0144] Similarly, in preparing a multi-component composition where
the Exemplary Composition is a liquid, a rinse or an aerosol spray,
the base compound selected may be dissolved in deionize or purified
water in a separate preparation. This solution may be mixed with
the chlorite ion source in an aqueous solution. The remaining
ingredients, e.g. sweetening agents, flavoring agents, fluoride ion
source, additional deionized or purified water, and/or other
ingredients as described above and as applicable, are added one by
one in appropriate amounts. The N-acyl sarcosinate such as sodium
lauroyl sarcosinate may be added prior to adding the weak acid
while preparing the composition. The appropriate amount of weak
acid may be dissolved in water and the appropriate quantity may be
mixed with the composition to maintain the final pH of the overall
formulation in the range of 6.0 to 8.5. The base compound and the
weak acid of the composition constitute the buffering system as
defined herein. All compounding may be required to occur at ambient
temperatures to maintain the stability of the composition.
[0145] In preparing a multi-component composition where the
Exemplary Composition is a liquid spray, the method for preparation
follows the method for oral rinse composition taught above, wherein
additional ingredients such as dispersing agents, humectants, or
preservatives are mixed with the composition prior to adjusting the
pH of the final composition in the range of 6.0 to 8.5.
Example 1. Formulations of a Toothpaste Embodiment
[0146] Various compositions of Exemplary Composition I were
formulated and tested below. Toothpaste compositions and
ingredients thereof tested (Toothpaste A through H) are summarized
in Table 1. Table 2 provides a summary of the percentage weight to
total weight of each ingredient in Toothpastes A to H.
TABLE-US-00001 TABLE 1 Comparison Toothpaste Compositions
Ingredients Toothpaste Toothpaste Toothpaste Toothpaste Toothpaste
Toothpaste Toothpaste Toothpaste Ingredient A B C D E F G H
Chlorite Stabilized Stabilized Stabilized Stabilized Stabilized
Stabilized Stabilized Stabilized Ion Chlorine Chlorine Chlorine
Chlorine Chlorine Chlorine Chlorine Chlorine Source Dioxide Dioxide
Dioxide Dioxide Dioxide Dioxide Dioxide Dioxide Buffering
Na.sub.3HPO.sub.4 Na.sub.2HPO.sub.4 Na.sub.2HPO.sub.4
Na.sub.2HPO.sub.4 Na.sub.2HPO.sub.4 Na.sub.2HPO.sub.4
Na.sub.2HPO.sub.4 Na.sub.2HPO.sub.4 System or + + + + + + + pH
adjusting NaH.sub.2PO.sub.4 NaH.sub.2PO.sub.4 NaH.sub.2PO.sub.4
NaH.sub.2PO.sub.4 NaH.sub.2PO.sub.4 NaH.sub.2PO.sub.4
NaH.sub.2PO.sub.4 agent Humectant(s) Glycerin Sorbitol -- -- -- --
Sorbitol -- + Sorbitol Aliphatic -- -- Sodium Sodium Sodium Sodium
Sodium -- anionic Lauroyl Lauroyl Cocoyl Myristoyl Lauroyl compound
Sarcosinate Sarcosinate Sarcosinate Sarcosinate Sarcosinate Source
of -- Sodium Sodium -- Sodium Sodium Sodium Sodium Fluoride
Fluoride Fluoride Fluoride Fluoride Fluoride Fluoride Thickening
Cellulose Cellulose Cellulose Cellulose Cellulose Cellulose
Cellulose Cellulose Agent Gum Gum Gum Gum Gum Gum Gum Gum Coloring
Titanium Titanium Titanium Titanium Titanium Titanium Titanium
Titanium Agent Dioxide Dioxide Dioxide Dioxide Dioxide Dioxide
Dioxide Dioxide (whitening) Abrasive Hydrated Hydrated Hydrated
Hydrated Hydrated Hydrated Hydrated Hydrated Agent Silica Silica
Silica Silica Silica Silica Silica Silica Flavoring Peppermint
Peppermint Peppermint Peppermint Peppermint Peppermint Peppermint
Peppermint Agents(s) oil oil oil oil oil oil oil oil + + + + + + +
+ Spearmint Menthol Menthol Menthol Menthol Menthol Menthol Menthol
oil Crystals Crystals Crystals Crystals Crystals Crystals Crystals
+ Menthol Crystals Sweetener Sodium Sucralose Sucralose Sucralose
Sucralose Sucralose Sucralose Sucralose Saccharin Water Water Water
Water Water Water Water Water Water Note: Na.sub.3HPO.sub.4:
Trisodium phosphate. Na.sub.2HPO.sub.4: Disodium hydrogen
phosphate. NaH.sub.2PO.sub.4: Sodium dihydrogen phosphate.
TABLE-US-00002 TABLE 2 Toothpaste Compositions Toothpaste
Toothpaste Toothpaste Toothpaste Toothpaste Toothpaste Toothpaste
Toothpaste A B C D E F G H Ingredient (% w/w) (% w/w) (% w/w) (%
w/w) (% w/w) (% w/w) (% w/w) (% w/w) Stabilized 0.14 0.14 0.14 0.14
0.14 0.14 0.14 0.14 Chlorine Dioxide Trisodium 1.0 -- -- -- -- --
-- -- phosphate Disodium -- 1.6 2.4 2.4 2.4 2.4 2.4 2.4 hydrogen
phosphate + Sodium dihydrogen phosphate Glycerin 10.0 -- -- -- --
-- -- -- Sorbitol 31.2 15.0 -- -- -- -- 15.0 -- Sodium -- -- 2.5
2.5 -- -- 2.5 -- Lauroyl Sarcosinate Sodium -- -- -- -- 2.5 -- --
-- Cocoyl Sarcosinate Sodium -- -- -- -- -- 2.5 -- -- Myristoyl
Sarcosinate Sodium -- 0.24 0.24 -- 0.24 0.24 0.24 0.24 Fluoride
Cellulose 1.2 1.9 1.9 1.9 1.9 1.9 1.9 1.9 Gum Titanium 0.95 0.95
0.95 0.95 0.95 0.95 0.95 0.95 Dioxide Hydrated 26.0 26.0 26.0 26.0
26.0 26.0 26.0 26.0 Silica Peppermint 0.9 0.9 0.9 0.9 0.9 0.9 0.9
0.9 oil + Menthol Crystals Sucralose -- 0.1 0.2 0.2 0.2 0.2 0.2 0.2
Sodium 0.27 -- -- -- -- -- -- -- saccharin Water 28.34 53.17 64.77
65.01 64.77 64.77 49.77 67.27
Example 2: Accelerated Stability Testing of Toothpastes A, B, C,
and D
[0147] Toothpaste A was prepared following the teachings of U.S.
Pat. Nos. 5,200,171, 5,348,734, and 5,489,435. pH of the
composition containing stabilized chlorine dioxide was adjusted
using only one pH adjusting agent, which is a. phosphate salt,
trisodium phosphate. Toothpaste A contained glycerol and sorbitol
as humectants.
[0148] Toothpaste B was prepared following the teachings of U.S.
Patent Application U.S. 2011/0318282. Toothpaste B contained
sorbitol as humectant but did not contain glycerol.
[0149] Toothpastes C, E, and F were prepared following the teaching
as described herein and according to Exemplary Composition I,
wherein the stabilized chlorine dioxide compositions were free of
both glycerol and sorbitol and contained N-acyl sarcosinate, an
aliphatic anionic compound, such as sodium lauroyl sarcosinate,
sodium cocoyl sarcosinate, and sodium myristoyl sarcosinate,
respectively.
[0150] Toothpaste D was prepared following the teaching as
described herein, that is, that it was identical to Toothpaste C
except for the absence of any fluoride ion source.
[0151] Toothpaste G was prepared following the teaching as
described herein and according to Exemplary Composition I, wherein
the multi-component composition contained sorbitol and sodium
lauroyl sarcosinate.
[0152] Toothpaste H was prepared following the teaching as
described herein and according to Exemplary Composition I, wherein
the stabilized chlorine dioxide composition was free of sorbitol
and an aliphatic anionic compound.
[0153] Accelerated stability testing of Toothpaste A, Toothpaste B,
Toothpaste C, and Toothpaste D were performed at 40.+-.2.degree. C.
and 70-75% relative humidity ("RH"). The results are summarized in
Table 3. Accelerated stability testing at 40.degree.
C..+-.2.degree. C. and 75%.+-.5% RH is a standard accelerated
stability test conducted in the pharmaceutical and cosmetic
industries (Guidance for Industry: Q1A(R2) Stability Testing of New
Drug Substances and Products, FDA, Revision 3 Nov. 2003). Oral care
compositions claimed to maintain stable amounts of the chlorite ion
at 25.degree. C. for one year or 40.degree. C. for 3 months is
described in U.S. Pat. No. 6,696,047. The stability testing of the
compositions of Exemplary Composition I adheres to accepted norms
of prior art and the pharmaceutical industry.
TABLE-US-00003 TABLE 3 Comparison of stability of toothpaste
compositions at 40.degree. .+-. 1.degree. C. and 70-75% RH Initial
1 Month 2 Months 3 Months 6 months SCD* SCD Loss SCD Loss SCD Loss
SCD Loss Composition (%) (%) (%) (%) (%) (%) (%) (%) (%) Toothpaste
A 0.077 0.019 75.3 0.005 93.5 0.0025 96.7 NT.sup..sctn. NT
(Teachings of U.S. Pat. Nos. 5,200,171; 5,348,734; and 5,489,435)
Toothpaste B 0.114 0.097 14.9 0.072 36.8 0.049 57.0 NT NT (U.S.
2011/0318282) Toothpaste C 0.12 0.12 0.0 0.11 8.3 0.10 16.6 0.09
25.0 (Exemplary Composition I) Toothpaste D 0.12 0.11 8.3 0.11 8.3
0.10 16.6 0.08 33.3 (Exemplary Composition I) *SCD: Stabilized
chlorine dioxide NT.sup..sctn.: Not Tested. The stability study for
Toothpastes A and B was discontinued after observing unacceptable
loss of 96.7% and 57.0% in 3 months.
[0154] As Table 3 shows, Toothpaste C and Toothpaste D provide much
greater shelf-life stability than Toothpaste A and Toothpaste B as
taught by prior art. Only 16.6% loss of stabilized chlorine dioxide
in 3 months was observed for Toothpaste C and Toothpaste D. In
contrast, Toothpaste A and Toothpaste B exhibited 96.7% and 57.0%
loss of stabilized chlorine dioxide, respectively, in 3 months. The
75.3% loss of stabilized chlorine dioxide from Toothpaste A in 1
month demonstrates that the shelf life stability of Toothpaste A is
less than 4 months at room temperature. Similarly, 36.8% loss of
stabilized chlorine dioxide from Toothpaste B in 2 months
demonstrates that the shelf life of Toothpaste B is less than 8
months at room temperature. Thus, both Toothpaste A and Toothpaste
B do not provide shelf life stability of stabilized chlorine
dioxide for a reasonable period of time, as defined herein, that is
desirable for an over-the-counter consumer product. Importantly,
25.0% and 33.3% losses of stabilized chlorine dioxide in Toothpaste
C and Toothpaste D after six months at 40.degree. C., respectively,
indicate that Toothpaste C and Toothpaste D have a shelf life of at
least 24 months (2 years) at room temperature.
Example 3. Accelerated Stability Testing of Toothpastes A-H
[0155] Without being limited by scientific theory, the stability
demonstrated by Toothpaste C and Toothpaste D is believed to be
attributed to the inclusion of an aliphatic anionic compound in the
multi-component composition, such as sodium lauroyl sarcosinate.
The achieved stability of the chlorine dioxide in Toothpaste C and
Toothpaste D is an unexpected result based on the tendency of
chlorine dioxide to decompose or react with other components. Of
note, the toothpaste embodiments, as tested, demonstrated a stable
shelf-life for a single-phase composition comprising an oxidative
compound, an aliphatic anionic compound, a buffering system, and
carriers of the composition. Toothpaste C and D were stable for a
reasonable period of time, e.g., from the time of compounding to a
normal time of usage for topical OTC oral care products. The
discovery of the effect of sodium lauroyl sarcosinate in increasing
the stability of stabilized chlorine dioxide in Toothpaste C and
Toothpaste D of Exemplary Composition I compared to Toothpaste A
and Toothpaste B of the prior art is an unexpected result.
[0156] Further experiments were performed to verify the stabilizing
benefit of an N-acyl sarcosinate with an oxidative compound.
Toothpaste compositions containing N-acyl sarcosinate compounds
such as sodium lauroyl sarcosinate (Toothpaste C), sodium cocoyl
sarcosinate (Toothpaste E), and sodium myristoyl sarcosinate
(Toothpaste F), as discussed in Exemplary Composition I were
prepared and tested for their stability. Additionally, toothpaste
containing N-acyl sarcosinate and sorbitol (Toothpaste G) and that
does not contain sorbitol as well as N-acyl sarcosinate (Toothpaste
H) were prepared and tested for their stability. The results are
summarized in Table 4.
TABLE-US-00004 TABLE 4 Comparison of stability of Toothpastes
prepared with different N-acyl sarcosinate compounds at 40.degree.
.+-. 1.degree. C. and 70-75% RH Initial 2 Month 3 Month N-Acyl SCD*
SCD Loss SCD Loss Composition Humectant Sarcosinate (%) (%) (%) (%)
(%) Toothpaste A Sorbitol + None 0.077 0.005 93.5 0.0025 96.7
Glycerin Toothpaste B Sorbitol None 0.114 0.072 36.8 0.049 57.0
Toothpaste C None Sodium 0.12 0.11 8.3 0.10 16.6 lauroyl
sarcosinate Toothpaste E None Sodium 0.14 0.14 0 0.13 9.3 cocoyl
sarcosinate Toothpaste F None Sodium 0.13 0.13 0 0.14 0 myristoyl
sarcosinate Toothpaste G Sorbitol Sodium 0.14 0.13 7.3 0.13 9.5
lauroyl sarcosinate Toothpaste H None None 0.13 0.13 0 0.13 9.5
*SCD: Stabilized chlorine dioxide
[0157] Toothpastes C, E and F containing sodium lauroyl
sarcosinate, sodium cocoyl sarcosinate sodium myristoyl sarcosinate
exhibited 16.6%, 9.3% and 0% loss in the stabilized chlorine
dioxide after 3 months at 40.+-.1.degree. C. and 70-75% RH,
respectively. As discussed earlier, the stability for 3 months at
40.+-.1.degree. C. and 70-75% RH corresponds to 1 year of shelf
life at room temperature. The loss of stabilized chlorine dioxide
in 3 months at 40.+-.1.degree. C. and 70-75% RH for toothpastes A
and B prepared following teachings of prior art was 96.7% and
57.0%, respectively. Measurement variability in estimation of
chlorine dioxide by titration method is about 10%. Therefore, any
loss >10% is considered as observed loss. The results
demonstrate that N-acyl sarcosinate compounds significantly
enhanced the stability of stabilized chlorine dioxide. Toothpaste G
that contains both sorbitol and sodium lauroyl sarcosinate
exhibited 9.5% loss in stabilized chlorine dioxide in 3 months at
40.+-.1.degree. C. and 70-75% RH. Similarly, Toothpaste H that does
not contain sorbitol exhibited 9.5% loss in stabilized chlorine
dioxide in 3 months at 40.+-.1.degree. C. and 70-75% RH. The
results confirm prior art that polyhydroxy compounds such as
sorbitol and glycerin react with chlorite salts thereby resulting
in unstable compositions.
[0158] In addition to the stability of stabilized chlorine dioxide
consumer goodness properties such as flavor, taste, and consistency
of the toothpaste are important for preparing a marketable
composition. Viscosity of the toothpaste preparations was
determined using Spindle 1 at 30 rpm. The results are summarized in
Table 5:
TABLE-US-00005 TABLE 5 Viscosity of toothpaste preparations
Viscosity Composition (Spindle 1 at 30 rpm) Toothpaste A 1531 cp
Toothpaste B 1538 cp Toothpaste C 1544 cp Toothpaste E 1625 cp
Toothpaste F 1263 cp Toothpaste G 2306 cp Toothpaste H 713 cp
[0159] The viscosity data in Table 5 demonstrate significant
differences for Toothpastes A-H. Viscosity of Toothpaste H was
significantly lower (713 cp) compared to other toothpaste
preparations, particularly Toothpastes A through F (range 1263
cp-1625 cp). Further, Toothpaste H did not form a uniform ribbon of
toothpaste and did not hold or rest very well on a toothbrush. Such
preparation does not meet the consumer goodness characteristics for
a consumer product. On the other hand, viscosity of Toothpaste G
was significantly higher (2306 cp) compared to other toothpaste
preparations, particularly Toothpastes A through F (range 1263
cp-1625 cp). Toothpaste G was hard to squeeze out from the tubes at
its viscosity and did not form a uniform ribbon. Accordingly, this
level of viscosity renders it unsuitable as toothpaste. Thus,
Toothpastes C, D, E and F exemplify the stability, shelf-life and
viscosity characteristics of a desired toothpaste embodiment.
Example 4: Enamel Fluoride Uptake and Remineralization and
Demineralization
[0160] The following study was performed to determine the efficacy
of an embodiment to (a) promote enamel fluoride uptake and (b)
promote lesion remineralization under dynamic conditions simulating
in vivo caries formation. The model and methods used are described
in the literature (White 1987, 1988; Schemehorn et. al. 1990, 1992,
1994).
[0161] Test Products: US Pharmacopoeia Reference Standard for
fluoride toothpaste i.e. Fluoride Dentifrice: Sodium
Fluoride/Silica, Catalog No. 127752 was procured from US
Pharmacopoeia store, 12601 Twinbrook Parkway, Rockville, Md.
20852-1790. Crest 3D White Mild Mint and Colgate Total Advanced
Whitening Toothpaste were purchased from a local store. Toothpaste
B was prepared following the teachings of U.S. Patent Application
U.S. 2011/0318282. Toothpaste C was prepared following the teaching
as described herein and according to Exemplary Composition I.
[0162] Specimen Preparation: Enamel specimens (3 mm diameter) were
removed from extracted bovine teeth and mounted in rods. The
specimens were ground and polished to a high luster with Gamma
Alumina using standard methods. Eighteen specimens per group were
prepared for this study.
[0163] Initial Decalcification: Artificial lesions were formed in
the enamel specimens by a 33-hour immersion into a solution of 0.1
M lactic acid and 0.2% Carbopol C907 which was 50% saturated with
hydroxyapatite and adjusted to pH 5.0. The lesion surface hardness
range was 25-45 Vickers micro-hardness (VHN; 200 gF, 15 s dwell
time) and average lesion depth was approximately 70 .mu.m.
[0164] Remineralizing Solution: Pooled Human Saliva (collected
fresh from multiple donors, pooled and kept frozen until time of
use) was used as the remineralizing solution. Fifteen (15) ml of
remineralizing solution was placed into color codes 30 ml treatment
beakers. Fresh saliva was used each day (changed during the acid
challenge period).
[0165] Treatment Slurries: During the treatment period, the
specimens were immersed in dentifrice slurries to simulate daily
brushing. The slurries were prepared by adding 5.0 g of Toothpaste
B or Toothpaste C to 10 g of deionized water in a beaker with a
magnetic stirrer. Fresh slurries were prepared for each of the two
carriers just prior to each treatment.
[0166] Treatment Regimen: The cyclic treatment regimen consisted of
a 4.0 hour/day acid challenge in the lesion forming solution
described above with four, one-minute dentifrice treatment periods.
After the treatments, the specimens were rinsed with running
distilled water and then replaced back into the human saliva. The
remaining time (.about.20 hours) the specimens were in the human
saliva. The regimen was repeated for 10 days and interim Surface
Micro-Hardness (SMH) measurements were obtained. The specimens were
then subject to an additional 10 days of the treatment regimen for
a total of 20 days. The treatment schedule used for this experiment
was as follows (on the first day, Step 1 was not given; the test
began with one hour in human saliva to permit pellicle development
prior to any treatments):
TABLE-US-00006 Step 1- 8:00 a.m.-8:01 a.m. Dentifrice treatment
Step 2:- 8:01 a.m.-9:00 a.m. Remineralizing treatment Step 3:- 9:00
a.m.-9:01 a.m. Dentifrice treatment Step 4:- 9:01 a.m.-10:00 a.m.
Remineralizing treatment Step 5:- 10:00 a.m.-2:00 p.m. Acid
challenge Step 6:- 2:00 p.m.-3:00 p.m. Remineralizing treatment
Step 7:- 3:00 p.m.-3:01 p.m. Dentifrice treatment Step 8:- 3:01
p.m.-4:00 p.m. Remineralizing treatment Step 9:- 4:00 p.m.-4:01
p.m. Dentifrice treatment Step 10:- 4:01 p.m.-8:00 a.m.
Remineralizing treatment Step 11:- Back to Step 1
[0167] Fluoride Analysis: At the end of the 20-day treatment
regimen, the fluoride content of each enamel specimen was
determined using the micro-drill technique to a depth of 100 .mu.m.
Fluoride data were calculated as .mu.g F/cm.sup.3 (.mu.g F X
dilution factor/volume of drilling).
[0168] Remineralization Measurements: Both 10-day and 20-day
Surface Micro Hardness (SMH) assessments were conducted. The
difference between the hardness following treatment and initial
lesion hardness indicated the ability of that treatment to enhance
remineralization.
[0169] Results: The fluoride uptake data is summarized in Table 6
and FIG. 1 and the summary of surface hardness changes representing
remineralization is presented in Table 7 and FIG. 2. Statistical
analyses were performed with a one-way analysis of variance model
using Sigma Plot Software (13.0). Since significant differences
were indicated, the individual means were analyzed by the Student
Newman Keuls (SNK) test.
TABLE-US-00007 TABLE 6 Incipient Lesion Fluoride Uptake Fluoride
Uptake (.mu.g F/cm.sup.3) Toothpaste Mean (n = 18) SEM Crest 3D
White Mild Mint 1389 .+-.64 Colgate Total Advanced 2697 .+-.174
Whitening US Pharmacopoeia Reference 2857 .+-.187 Dentifrice
Toothpaste B 3451 .+-.202 Toothpaste C 5603 .+-.365
[0170] Toothpaste C exhibited 62.3% more fluoride uptake into
incipient lesioned enamel compared to Toothpaste B of U.S. Patent
Application U.S. 2011/0318282 (Table 6). Also, the fluoride uptake
by Toothpaste C was 96.1%, 107.7%, and 303.3% higher than US
Pharmacopoeia Reference Dentifrice, Colgate Total Advanced
Whitening, and Crest 3D White Mild Mint toothpastes, respectively
(Table 6). Combined effect of sodium lauroyl sarcosinate and
stabilized chlorine dioxide in enhancing fluoride uptake in tooth
enamel by Toothpaste C compared to Toothpaste B of prior art, US
Pharmacopoeia Reference Material, and commercial products is an
unexpected result.
TABLE-US-00008 TABLE 7 Surface Micro Hardness after 10 and 20 days
of remineralization treatment Surface Micro Hardness (SMH) Baseline
After 10 Days After 20 Days (Pre-Test) Change Change Toothpaste SMH
SMH in SMH SMH in SMH Crest 3D White Mild Mint 32.1 43.4 11.3 48.6
16.4 Colgate Total Advanced 32.1 45.4 13.3 50.5 18.4 Whitening
Toothpaste B 32.2 46.5 15.0 51.9 20.4 US Pharmacopoeia 32.1 48.9
16.8 56.3 24.2 Reference Dentifrice Toothpaste C 32.2 54.9 22.6
65.6 33.3
[0171] The protocol for the remineralization study involved
repeated acid challenge and remineralization treatment. Therefore,
net increased in Surface Micro-Hardness is combined result of
enhanced remineralization and reduced demineralization. Toothpaste
C exhibited 63.2% more remineralization after 20 days compared to
Toothpaste B of U.S. Patent Application U.S. 2011/0318282 (Table
7). Also, the remineralization after 20 days by Toothpaste C was
37.6%, 80.9%, and 103.0% higher than US Pharmacopoeia Reference
Dentifrice, Colgate Total Advanced Whitening, and Crest 3D White
Mild Mint toothpastes, respectively. The remineralization results
at 10 days and 20 days intervals were consistent further confirming
increased remineralization (Table 7). An unexpected discovery from
this study is the combined effect of sodium lauroyl sarcosinate and
stabilized chlorine dioxide in a multi-component composition
increased remineralization (combined result of enhanced
remineralization and reduced demineralization) as shown by the
enhanced fluoride uptake by Toothpaste C when compared to
Toothpaste B of prior art, US Pharmacopoeia Reference Material, and
the selected fluoride toothpaste commercial products.
Example 5: Pellicle Cleaning and Plaque Removal Study
[0172] The study below was performed to determine the plaque
removal capability of an embodiment as determined by removal of
stained pellicle. The method used was developed in order to assess
the ability of dentifrices to remove stained pellicle, i.e., to
determine the cleaning ability of complete dentifrice formulations.
Published studies demonstrate that the results of this test method
with dentifrice slurries were comparable to those obtained in
controlled clinical trials (Stookey et al. 1982). Thus, this
methodology is routinely used in the development of more effective
cleaning dentifrice formulations.
[0173] Test Product: Toothpaste B was prepared following the
teachings of U.S. Patent Application U.S. 2011/0318282. Toothpaste
C was prepared following the teaching as described herein. The
American Dental Association (ADA) reference material was procured
from Odontex Inc., Lawrence, Kans., USA.
[0174] Specimen Preparation: Bovine, permanent, central incisors
were cut to obtain labial enamel specimens approximately
10.times.10 mm. The enamel specimens were embedded in an
autopolymerizing methacrylate resin so that only the enamel
surfaces were exposed. The enamel surfaces were then smoothed and
polished on a lapidary wheel and lightly etched to expedite stain
accumulation and adherence. They were placed on a rotating rod
(.about.37.degree. C. incubator), which alternately exposed them to
air and to a solution having PGY broth, tea, coffee, mucin,
FeCl.sub.3, and Micrococcus luteus. The staining broth was changed
and specimens were rinsed daily until a uniform stain had
accumulated. After approximately seven days, a darkly stained
pellicle film was apparent on the enamel surfaces. Specimens were
rinsed, allowed to air dry, and refrigerated until used. All
products were tested using specimens prepared at the same time.
[0175] Scoring and Set-Up: The amount of in vitro stain was graded
photometrically using only the L value of the L*a*b* scale using a
spectrophotometer (Minolta CM2600d). The area of the specimens
scored was a 1/4-inch diameter circle in the center of the
10.times.10 mm enamel. Specimens with scores between 30 and 42 (30
being more darkly stained) were used. On the basis of these scores,
the specimens were divided into groups with each group having
approximately the same average baseline score.
[0176] Procedure: The specimens were mounted on a mechanical V-8
cross-brushing machine equipped with soft nylon-filament (Oral-B
40) toothbrushes. Tension on the enamel surface was adjusted to 150
g. The dentifrices were tested as slurries prepared by mixing 25
grams of dentifrice with 40 ml of deionized water. The American
Dental Association (ADA) Reference Material was the ADA abrasion
standard (10 g/50 ml of a 0.5% CMC solution). The specimens were
brushed for 800 strokes (4.5 minutes). To minimize mechanical
variables, ten specimens per group were brushed on each of the
eight brushing heads. Different test products were used on each
run, with one tube of slurry made up for each product. Fresh slurry
was made after being used to brush four specimens. Following
brushing, specimens were rinsed, blotted dry, and scored again for
stain, as previously described.
[0177] Calculations: The difference between the pre- and
post-brushing stain scores was determined and the mean and standard
error of measurement (SEM) was calculated for the reference group
in each study. The mean decrement between the pre- and
post-brushing stain scores was determined for the ADA Reference
Material group, and assigned a pellicle cleaning ratio (PCR) value
of 100. A constant value was calculated by dividing the mean
decrement of the ADA Reference Material into 100. The individual
PCR value for each specimen was calculated by multiplying its
individual decrement by the calculated constant.
[0178] The mean, standard deviation and SEM for each test group
were then calculated using the individual PCR values. The larger
the PCR value, the greater the amount of stained pellicle removed
from the enamel surface in this test. Data exhibiting outlier
values was not considered for calculating pellicle cleaning ratio.
The mean and SEM for each group was then calculated using the
individual cleaning ratios. Data was analyzed using a one-way
analysis of variance model (IBM SPSS Statistics 24 Software). Data
was further analyzed doing all pairwise multiple comparison
procedures (Student-Newman-Keuls method). All analyses were done
with the significance level set at 0.05.
[0179] Results: Initially, the studies were conducted with 15
replicates (n=15) of each sample.
[0180] The mean pellicle cleaning ratio of Toothpaste B, Toothpaste
C, and ADA Reference Material were 95.9, 101.21, and 100.0,
respectively. Further, the SEM around the mean was +2.46, +2.83,
and +2.85, respectively. Therefore, Toothpaste C was most effective
in removing removal of stained pellicle followed by to ADA
reference material and Toothpaste B. It is important to note that
Toothpaste C exhibited 5.5% higher mean pellicle cleaning ratio on
numerical basis compared to Toothpaste B. However, the difference
was not statistically significant since the p value for the
difference between the SEM around the mean for groups was >0.05.
Because the testing was conducted with the routine number of
replicates, the novel discovery of the current invention was not
disclosed through routine testing protocol.
[0181] The inventors repeated studies using 80 replicates (n=80) to
provide a sufficiently robust number of replicates to account for
the variability associated with the standard error of measurement
(SEM) and allow the outcomes of the discovery to be revealed as
statistically significant. The results are summarized in the Table
8.
TABLE-US-00009 TABLE 8 Pellicle Cleaning Ratio of Dentifrices
Pellicle Cleaning Ratio Toothpaste n Mean SEM Toothpaste B 76 94.48
.+-.1.12 ADA Reference Material 75 100.00 .+-.1.20 Toothpaste C 75
103.51 .+-.0.96
[0182] The observation that Toothpaste C was most effective in
removal of stained pellicle compared to ADA reference material and
Toothpaste B was affirmed with the higher number of replicates.
Further, Toothpaste B was less effective in removal of stained
pellicle compared to ADA reference material. Importantly, the
p-value for the difference between the groups was <0.05.
Therefore, removal of stained pellicle Toothpaste C compared to
Toothpaste B of U.S. Patent Application U.S. 2011/0318282 and ADA
Reference Material was statistically significant. Combined effect
of sodium lauroyl sarcosinate and stabilized chlorine dioxide in
enhancing removal of stained pellicle that corresponds to plaque
removal from tooth enamel by Toothpaste C compared to Toothpaste B
of prior art and ADA Reference Material is an unexpected result.
The results demonstrate that the results of Toothpaste C were
unexpected over the prior art.
Example 6: Regrowth of Oral Polymicrobial Biofilm
[0183] The following study was performed to determine the effect of
an embodiment on preventing 24 hours regrowth of oral polymicrobial
biofilm containing a mixed salivary bacterial preparation on bovine
enamel surfaces.
[0184] Test Product: Toothpaste C was prepared following the
teaching as described herein.
[0185] Experimental Design: 4.times.4 mm bovine enamel sections
(embedded in 12.times.12.times.7 mm acrylic resin) were prepared
for use in sterile 12 well tissue culture plates and sterilized by
ethylene oxide (EtO). Three ml of Brain Heart Infusion broth
supplemented with Yeast Extract and Vitamin K and hemin (BHI-YE)
was inoculated with 50 .mu.l of an overnight culture of a mixed
species whole salivary bacterial preparation in the wells of the
tissue culture plate containing the sections (1 section/well). The
plates were incubated for 24 hours to grow the biofilm on the
enamel. In order to remove the biofilm similar to a human subject
brushing his/her teeth the sections were brushed with Toothpaste C
(3 sections/paste) for a brushing schedule similar to a 30 second
brushing by human subjects. The sections were rinsed with sterile
water and inserted into a fresh tissue culture plate containing 3
ml of BHI-YE to facilitate regrowth of the remaining oral biofilm
on the enamel sections. The plates were incubated for 24 hours. The
sections were removed, placed in 2 ml of sterile saline, sonicated
for 10 sec, vortexed for 10 sec, diluted to 1:10 and 1:1000 and
spiral plated on blood agar plates. After 24 hours of incubation,
the colonies on the agar plates were counted using an automated
colony counter. The methods are described in published literature
(Huang et al. 2012 and Sabrah et al. 2015).
[0186] Results: The results of the biofilm viability (CFU/ml) assay
are presented in Table 9.
TABLE-US-00010 TABLE 9 Regrowth of Oral Polymicrobial Biofilm Mean
Group Mean p value compared Sample number CFU/ml CFU/ml to Control
Toothpaste C-1 1.04 .times. 10.sup.7 5.08 .times. 10.sup.7 0.018
Toothpaste C-2 1.39 .times. 10.sup.8 Toothpaste C-3 3.18 .times.
10.sup.6 Control-1 8.31 .times. 10.sup.7 13.1 .times. 10.sup.7 NA
Control-2 9.96 .times. 10.sup.7 Control-3 2.09 .times. 10.sup.8
[0187] There was a significant reduction in regrowth of oral
polymicrobial biofilm obtained by Toothpaste C compared to the
water brushed control (p<0.05). Regrowth of oral polymicrobial
biofilm is directly proportional to quantity of residual bacteria
after brushing. Therefore, the results demonstrate the Toothpaste C
is highly effective killing bacteria in oral polymicrobial
biofilm.
Example 7: Spectrometric Analysis of the Embodiments
[0188] The following study was performed to determine the quantity
of chlorite ion available in an embodiment of the present
disclosure. Such available quantity of chlorite ion and not the
stabilized chlorine dioxide is important for reaction with the
salivary biomolecules in the oral cavity. The methodology used was
standard UV-visible spectrometry.
[0189] Test Products: Toothpaste B was prepared following the
teachings of U.S. Patent Application U.S. 2011/0318282. Toothpaste
C was prepared following the teaching as described herein. Sodium
chlorite was purchased from Sigma-Aldrich, 3050 Spruce St., St.
Louis, Mo. 63103.
[0190] Specimen Preparation: 0.02 mM phosphate buffer pH 7.0 was
prepared using HPLC grade water. 200 mg of toothpaste A and
toothpaste B was suspended in 3.0 ml of 0.02 mM phosphate buffer pH
7.0 and homogenized thoroughly using rotamix. The homogenous
mixture was then centrifuged at 3,500 rpm for 30 minutes. Clear
supernatant was collected. Aqueous toothpaste extracts were used
for spectrophotometric analysis. Each toothpaste product was
processed in 5 replicates. pH adjusted HPLC-grade water served as a
suitable control for recording the spectra.
[0191] Recording of Spectra: Zero-order electronic absorption
spectra of aqueous extracts of toothpaste products and aqueous
authentic sodium chlorite (Na.sup.+/ClO.sub.2.sup.-) solution were
recorded on a PC-controlled Jasco V730 UV-visible spectrophotometer
at a pH value of 7.0 (scan rate 120 nm/min). From the extinction
coefficient (.xi.) values of ClO.sub.2.sup.- and OCl.sup.- (at max
values of 262 and 292 nm, respectively), multivariate spectral
curve resolution analysis of datasets consisting of a range of oral
dilutions were subjected to multivariate curve resolution (MCR)
analysis for determining the concentration of chlorite ion
(ClO.sub.2.sup.-; predominant active agent).
[0192] Results: Electronic absorption spectra of Toothpaste B and
Toothpaste C are presented in FIG. 3 and FIG. 4, respectively.
[0193] Both Toothpaste B and Toothpaste C showed two clear
absorption bands located at 262 nm and 295 nm. Absorption peak at
262 nm corresponds to active chlorite anion and the peak at 295 nm
is attributed to hypochlorite anion generated from the
decomposition of chlorite, and/or chemical reaction of chlorite
with other ingredient in the toothpaste. Absorbance peak of
chlorite ion (ClO.sub.2) at 262 nm of Toothpaste B was 0.155 and
that for Toothpaste C was 0.255. Higher absorbance in Toothpaste C
demonstrates 64.5% higher quantity of available chlorite ion
(ClO.sub.2) compared to Toothpaste B. Such higher quantity of
available chlorite ion by Toothpaste C compared to Toothpaste B of
prior art is an unexpected result. The results demonstrate that the
results of Toothpaste C were unexpected over the prior art. Not to
be bound by any particular theory, a benefit of having 64.5% more
available chlorite ion is that it is available for its increased
effect in the oral cavity. This result of the use of compositions
as taught by this embodiment is further proved by oxidation of
salivary biomolecules such as pyruvate and L-methionine as
described in Example 8.
Example 8: Oxidation of Salivary Biomolecules by .sup.1H NMR
Analysis
[0194] The following study was performed to determine the efficacy
of an embodiment of the present disclosure for oxidation of
biomolecules in saliva. Oxidation of pyruvate to acetate and
L-methionine to methionine sulfoxide was monitored by .sup.1H NMR
spectroscopy.
[0195] Test Products: Toothpaste B was prepared following the
teachings of U.S. Patent Application U.S. 2011/0318282. Toothpaste
C was prepared following the teaching as described herein.
[0196] Aqueous Toothpaste Extract Preparation: 0.02 mM phosphate
buffer pH 7.0 was prepared using HPLC grade water. 200 mg of
Toothpaste B and Toothpaste C was suspended in 3.0 ml of 0.02 mM
phosphate buffer pH 7.0 and homogenized thoroughly using rotamix.
The homogenous mixture was then centrifuged at 3,500 rpm for 30
minutes. Clear supernatant was collected. Aqueous toothpaste
extracts thus prepared was used for the study.
[0197] Human Saliva Sample Preparation: 0.6 ml of aqueous extract
of the toothpaste composition to be tested was mixed with 0.6 ml of
aliquots of each salivary supernatant sample collected from healthy
volunteers (n=10). After thorough rotamixing, these mixtures were
equilibrated at a temperature of 35.degree. C. for 30 and 60 second
periods, and then stored at -80.degree. C. for a maximal duration
of 72 hours prior to .sup.1H NMR analysis. 0.6 ml aliquots of each
salivary supernatant sample mixed with 0.6 ml of HPLC-grade water
(previously thoroughly sparged with Helium gas for a 30 min.
period) in place of the extracts of toothpaste products and then
also equilibrated and stored in the same manner served as essential
controls.
[0198] Time Dependent Oxidation of Pyruvate to Acetate and
Methionine to Methionine Sulfoxide: Aqueous solutions containing
0.02 mM of sodium pyruvate and L-methionine were prepared in 0.05
mM phosphate buffer (pH 7.0) and rigorously deoxygenated via
purging with Helium gas for 30 mins at ambient temperature prior to
use. 1.00 ml aliquots of this solution were individually treated
with equivalent volumes of aqueous extract of the toothpaste
composition. The mixture was then equilibrated at a temperature of
35.degree. C. for 30 and 60 seconds and stored at -80.degree. C.
for a maximal period of 72 hours prior to the acquisition of
.sup.1H NMR spectra. 1.0 ml aliquots of sodium pyruvate or
L-methionine solution treated with an equivalent volume of
HPLC-grade water equilibrated and stored in the same manner served
as respective control.
[0199] .sup.1H NMR Measurements: A 0.60 ml aliquot of sample
prepared as described above was placed in 5-mm diameter NMR tubes
and 0.1 ml of a 0.00225 mM solution of sodium
3-trimethylsilyl-(2,2,3,3-2H4)-1-propionate [TSP, internal chemical
shift reference and quantitative .sup.1H NMR internal standard
(.delta.=0.00 ppm)] in deuterium oxide (.sup.2H.sub.2O) was added,
the latter to provide a field frequency lock. Single-pulse and/or
Carr-Purcell-Meiboom-Gill (CPMG) spin-echo .sup.1H NMR spectra was
acquired on a Bruker Avance AV-400 spectrometer at an operating
frequency of 399.94 MHz and a probe temperature of 293 K. The
one-dimensional (1D) NOESY pulse sequence with presaturation of the
biofluid water signal were employed throughout. Chemical shift
values were referenced to the added TSP for these samples, together
with the --CH.sub.3 group signals of selected biomolecules
detectable. All .sup.1H NMR spectra were acquired in duplicate, a
random order and an automated manner using a sample changer for
continuous sample delivery. Two-dimensional (2D) shift-correlated
.sup.1H-.sup.1H spectra of biofluid samples were also acquired.
[0200] Results: .sup.1H NMR-linked metabolomics analysis of human
salivary sample supernatants revealed that aqueous extracts from
Toothpaste C formulation was reproducibly more effective than those
from Toothpaste B in oxidation of pyruvate to acetate and
methionine to methionine sulfoxide. The observation was further
confirmed by a time dependent study wherein solutions of sodium
pyruvate and methionine were treated with aqueous extracts of
Toothpaste B and Toothpaste C each for 30 and 60 seconds. The
results are summarized in Table 10.
TABLE-US-00011 TABLE 10 Oxidation of Salivary Biomolecules as
Determined by .sup.1H NMR Study Oxidation of Sodium Oxidation of
L-Methionine Pyruvate [Methionine [Acetate]:[Pyruvate] Ratio
Sulfoxide]:[Methionine] Time Toothpaste B Toothpaste C Toothpaste B
Toothpaste C 0 Seconds 0.149 .times. 10.sup.-3 0.149 .times.
10.sup.-3 1.58 .times. 10.sup.-3 1.69 .times. 10.sup.-3 30 Seconds
1.30 .times. 10.sup.-3 9.57 .times. 10.sup.-3 5.55 .times.
10.sup.-3 13.0 .times. 10.sup.-3 60 Seconds 3.08 .times. 10.sup.-3
11.30 .times. 10.sup.-3 5.75 .times. 10.sup.-3 14.0 .times.
10.sup.-3
[0201] The ratio of concentrations of acetate:pyruvate within 30
and 60 seconds of interaction with Toothpaste C was 7.36 and 3.66
fold higher compared to Toothpaste B, respectively. Similarly, The
ratio of concentrations of methionine sulfoxide:methionine within
30 and 60 seconds of interaction with Toothpaste C was 2.34 and
2.43 fold higher compared to Toothpaste B, respectively. The
results demonstrate that Toothpaste C oxidized salivary
biomolecules at much faster rate and in greater quantity compared
to Toothpaste B.
[0202] Lower oxidizing activity of Toothpaste B is attributed to
the partial consumption of stabilized chlorine dioxide by sorbitol
present in it. The results are also aligned with the lower
stability of stabilized chlorine dioxide of Toothpaste B (as
presented in Table 3). Combined effect of sodium lauroyl
sarcosinate and stabilized chlorine dioxide in enhancing the
oxidation of salivary biomolecules by Toothpaste C compared to
Toothpaste B of prior art is an unexpected result. The results
demonstrate that Toothpaste C was more effective at oxidizing
sodium pyruvate and L-methionine over the prior art. Not to be
bound by a particular theory, the increased levels of sodium
chlorite seen in Example 7 may have led to the increased oxidation
reaction. Though this is true, this is not the only factor that can
contribute to the oxidation reaction. Physico-chemical properties
of other components in the embodiments may also contribute. For
example, sorbitol is known to react with chlorine dioxide.
Therefore, the oxidation reaction is less in Toothpaste B. In
contrast, available chlorine dioxide in Toothpaste C reacts with
only salivary biomolecules (in absence of sorbitol in the
composition). Further, altered microenvironment of hydrophilicity
due to an N-acyl sarcosinate may also contribute to higher
oxidation reaction.
[0203] Each of the exemplary compositions and those against which
they were compared were suitable for use as a prophylactic
treatment for cleaning the teeth, by applying the composition
formulated as a paste to the tooth surface when disposed in a tube
as employed by individuals in routine home oral hygiene procedures
of tooth brushing.
[0204] The detailed description shows embodiments by way of
illustration, including the best mode. While these embodiments are
described in sufficient detail to enable those skilled in the art
to practice the principles of the present disclosure, it should be
understood that other embodiments may be realized and that chemical
changes may be made without departing from the spirit and scope of
principles of the present disclosure. Thus, the detailed
description herein is presented for purposes of illustration only
and not of limitation. With regard to procedures, methods,
techniques, and workflows that are in accordance with some
embodiments, some operations in the procedures, methods,
techniques, and workflows disclosed herein may be combined and/or
the order of some operations may be changed. For example, the steps
recited in any of the method descriptions may be executed in any
suitable order and are not limited to the order presented.
[0205] In the above description, all cited references are
incorporated herein by reference in their entireties. The citing of
any reference is not an admission that such a reference is relevant
prior art; rather, citations are to reference the novelty of the
invention and discoveries described herein relative to known
scientific literature, practices and prior art. In the description
of the Present Invention, all ratios are weight ratios unless
specifically stated otherwise. Unless otherwise indicated or
evident from context, preferences indicated above and herein apply
to the entirety of the embodiments discussed herein.
[0206] In describing the present disclosure, the following
terminology will be used: The singular forms "a," "an," and "the"
include plural referents unless the context clearly dictates
otherwise. Thus, for example, reference to an item includes
reference to one or more items. The term "ones" refers to one, two,
or more, and generally applies to the selection of some or all of a
quantity. The term "plurality" refers to two or more of an item.
The term "about" means quantities, dimensions, sizes, formulations,
parameters, shapes and other characteristics need not be exact, but
may be approximated and/or larger or smaller, as desired,
reflecting acceptable tolerances, conversion factors, rounding off,
measurement error and the like and other factors known to those of
skill in the art. The term "substantially" means that the recited
characteristic, parameter, or value need not be achieved exactly,
but that deviations or variations, including for example,
tolerances, measurement error, measurement accuracy limitations and
other factors known to those of skill in the art, may occur in
amounts that do not preclude the effect the characteristic was
intended to provide.
[0207] Numerical data may be expressed or presented herein in a
range format. It is to be understood that such a range format is
used merely for convenience and brevity and thus should be
interpreted flexibly to include not only the numerical values
explicitly recited as the limits of the range, but also interpreted
to include all of the individual numerical values or sub-ranges
encompassed within that range as if each numerical value and
sub-range is explicitly recited. As an illustration, a numerical
range of "about 1 to 5" should be interpreted to include not only
the explicitly recited values of about 1 to about 5, but also
include individual values and sub-ranges within the indicated
range. Thus, included in this numerical range are individual values
such as 2, 3 and 4 and sub-ranges such as 1-3, 2-4 and 3-5,
etc.
[0208] This same principle applies to ranges reciting only one
numerical value (e.g., "greater than about 1") and should apply
regardless of the breadth of the range or the characteristics being
described. A plurality of items may be presented in a common list
for convenience. However, these lists should be construed as though
each member of the list is individually identified as a separate
and unique member. Thus, no individual member of such list should
be construed as a de facto equivalent of any other member of the
same list solely based on their presentation in a common group
without indications to the contrary. Furthermore, where the terms
"and" and "or" are used in conjunction with a list of items, they
are to be interpreted broadly, in that any one or more of the
listed items may be used alone or in combination with other listed
items. The term "alternatively" refers to selection of one of two
or more alternatives, and is not intended to limit the selection to
only those listed alternatives or to only one of the listed
alternatives at a time, unless the context clearly indicates
otherwise.
[0209] The scope should be determined by the appended claims and
their legal equivalents, rather than by the examples given above.
For example, the operations recited in any method claims may be
executed in any order and are not limited to the order presented in
the claims. Moreover, no element is essential unless specifically
described herein as "critical" or "essential."
[0210] Moreover, where a phrase similar to `at least one of A, B,
and C` or `at least one of A, B, or C` is used in the claims or
specification, it is intended that the phrase be interpreted to
mean that A alone may be present in an embodiment, B alone may be
present in an embodiment, C alone may be present in an embodiment,
or that any combination of the elements A, B and C may be present
in a single embodiment; for example, A and B, A and C, B and C, or
A and B and C.
* * * * *
References