U.S. patent application number 12/058278 was filed with the patent office on 2009-08-13 for oral care product and methods of use and manufacture thereof.
This patent application is currently assigned to COLGATE-PALMOLIVE COMPANY. Invention is credited to Virginia Monsul Barnes, Suman Chopra, Diane Cummins, Rajnish Kohli, Sergio Leite, Sarita V. Mello, Andre M. Morgan, Michael Prencipe, Richard Scott Robinson, Ralph Peter Santarpia, III, Eric A. Simon, Ravi Subramanayam, Richard J. Sullivan, Gary Edward Tambs, Qin Wang, Donghui Wu, Lynette Zaidel.
Application Number | 20090202450 12/058278 |
Document ID | / |
Family ID | 40056156 |
Filed Date | 2009-08-13 |
United States Patent
Application |
20090202450 |
Kind Code |
A1 |
Prencipe; Michael ; et
al. |
August 13, 2009 |
ORAL CARE PRODUCT AND METHODS OF USE AND MANUFACTURE THEREOF
Abstract
This invention relates to oral care compositions comprising an
effective amount of a basic amino acid in free or salt form,
together with an anionic surfactant, and to methods of using and of
making such compositions.
Inventors: |
Prencipe; Michael; (West
Windsor, NJ) ; Cummins; Diane; (Livingston, NJ)
; Subramanayam; Ravi; (Belle Mead, NJ) ; Sullivan;
Richard J.; (Atlantic Highlands, NJ) ; Santarpia,
III; Ralph Peter; (Edison, NJ) ; Mello; Sarita
V.; (Somerset, NJ) ; Zaidel; Lynette;
(Cranford, NJ) ; Chopra; Suman; (Monroe, NJ)
; Wang; Qin; (Monmouth Junction, NJ) ; Tambs; Gary
Edward; (Belle Mead, NJ) ; Barnes; Virginia
Monsul; (Ringoes, NJ) ; Wu; Donghui;
(Bridgewater, NJ) ; Morgan; Andre M.;
(Robbinsville, NJ) ; Kohli; Rajnish;
(Hillsborough, NJ) ; Robinson; Richard Scott;
(Belle Mead, NJ) ; Leite; Sergio; (Kendall Park,
NJ) ; Simon; Eric A.; (Somerset, NJ) |
Correspondence
Address: |
COLGATE-PALMOLIVE COMPANY
909 RIVER ROAD
PISCATAWAY
NJ
08855
US
|
Assignee: |
COLGATE-PALMOLIVE COMPANY
New York
NY
|
Family ID: |
40056156 |
Appl. No.: |
12/058278 |
Filed: |
March 28, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61027431 |
Feb 8, 2008 |
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61027420 |
Feb 8, 2008 |
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61027432 |
Feb 8, 2008 |
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Current U.S.
Class: |
424/50 ; 424/49;
424/52 |
Current CPC
Class: |
A61K 8/19 20130101; A61Q
11/00 20130101; A61P 9/00 20180101; A61P 37/04 20180101; A61K 8/24
20130101; A61P 1/02 20180101; A61K 8/21 20130101; A61K 31/198
20130101; A61K 8/44 20130101; A61P 31/04 20180101; A61P 31/02
20180101 |
Class at
Publication: |
424/50 ; 424/52;
424/49 |
International
Class: |
A61K 8/30 20060101
A61K008/30; A61K 8/19 20060101 A61K008/19; A61K 8/66 20060101
A61K008/66; A61Q 11/00 20060101 A61Q011/00 |
Claims
1. An oral care composition comprising a. an effective amount of a
basic amino acid, in free or salt form; b. an anionic surfactant;
and c. an additional agent selected from an effective amount of an
antibacterial agent; an effective amount of a fluoride source; an
anionic polymer; and combinations thereof.
2. A composition according claim 1 wherein the basic amino acid is
arginine.
3. A composition according to claim 1 wherein the basic amino acid
is in salt form and selected from arginine phosphate, arginine
bicarbonate, and arginine hydrochloride.
4. A composition according to claim 1 wherein the anionic
surfactant is selected from sodium lauryl sulfate and sodium
laureth sulfate and mixtures thereof.
5. A composition according to claim 1 wherein the anionic
surfactant is present in an amount of from about 0.01 to about 10
weight %.
6. A composition according to claim 1 wherein the anionic
surfactant is present in an amount of from about 0.3 to about 4.5
weight %.
7. A composition according to claim 1 comprising a fluoride source
selected from sodium fluoride and sodium monofluorophosphate.
8. A composition according to claim 1 further comprising an
antibacterial agent.
9. A composition according to claim 8 wherein the antibacterial
agent is triclosan.
10. A composition according to claim 1 further comprising an
anionic polymer.
11. A composition according to claim 10 wherein the anionic polymer
is a copolymer of methyl vinyl ether and maleic anhydride.
12. A composition according to claim 1 which is a dentifrice
comprising a. an effective amount of a salt of a basic amino acid
selected from arginine bicarbonate, arginine phosphate and arginine
hydrochloride; b. an effective amount of triclosan; c. an effective
amount of a soluble fluoride salt selected from sodium fluoride and
sodium monofluophosphate; d. an anionic surfactant selected from
sodium lauryl sulfate and sodium laureth sulfate.
13. A composition according to claim 1 further comprising
xylitol.
14. A composition according to claim 1 comprising a particulate
material selected from silica and calcium carbonate.
15. A composition according to claim 1 wherein the radioactive
dentin abrasion (RDA) is less than about 150.
16. The composition claim 1 in the form of a toothpaste further
comprising one or more of water, abrasives, surfactants, foaming
agents, vitamins, polymers, enzymes, humectants, thickeners,
antimicrobial agents, preservatives, flavorings, colorings and/or
combinations thereof.
17. A method comprising applying an effective amount of the oral
composition of claim 1 to the oral cavity of a subject in need
thereof to a. reduce or inhibit formation of dental caries, b.
reduce, repair or inhibit early enamel lesions, c. reduce or
inhibit demineralization and promote remineralization of the teeth,
d. reduce hypersensitivity of the teeth, e. reduce or inhibit
gingivitis, f. promote healing of sores or cuts in the mouth, g.
reduce levels of acid producing bacteria, h. to increase relative
levels of arginolytic bacteria, i. inhibit bacterial attachment or
microbial biofilm formation in the oral cavity, j. raise and/or
maintain plaque pH at levels of at least pH 5.5 following sugar
challenge, k. reduce plaque accumulation, l. treat dry mouth, m.
whiten teeth, n. enhance systemic health, including cardiovascular
health, e.g., by reducing potential for systemic infection via the
oral tissues, o. reduce erosion of the teeth, p. immunize the teeth
against cariogenic bacteria, and/or q. clean the teeth and oral
cavity.
18. The method of claim 17 to inhibit bacterial attachment or
microbial biofilm formation.
19. An oral care composition comprising a basic amino acid, in free
or salt form, and an anionic surfactant for reducing the adhesion
of bacteria to tooth surfaces in an oral cavity of a subject.
20. An oral care composition according to claim 19 wherein the
basic amino acid is present in an amount of from 0.1 to 20 wt % of
the total composition weight.
21. An oral care composition according to claim 19 wherein the
basic amino acid is present in an amount of from 1 to 10 wt % of
the total composition weight.
22. An oral care composition according to claim 19 wherein the
basic amino acid comprises arginine.
23. An oral care composition according to claim 19 further
comprising an antibacterial agent in an amount of from 0.01 to 5 wt
% of the total composition weight.
24. An oral care composition according to claim 23 wherein the
antibacterial agent is present in an amount of from 0.01 to 1 wt %
of the total composition weight.
25. An oral care composition according to claim 19 wherein the
antibacterial agent is triclosan.
26. An oral care composition according to claim 19 further
comprising a soluble fluoride salt in an amount of from 0.01 to 2
wt % of the total composition weight.
27. An oral care composition according to claim 19 further
comprising a source of fluoride ions in an amount to provide 50 to
25,000 ppm by weight of fluoride ions in the total composition
weight.
28. An oral care composition according to claim 26 wherein the
soluble fluoride salt is selected from sodium fluoride, sodium
monofluorophosphate, and mixtures thereof.
29. An oral care composition according to claim 19 wherein the
anionic surfactant is present in an amount of from 0.01 to 10 wt %
of the total composition weight.
30. An oral care composition according to claim 29 wherein the
anionic surfactant is present in an amount of from 0.3 to 4.5 wt %
of the total composition weight.
31. An oral care composition according to claim 29 wherein the
anionic surfactant is selected from sodium lauryl sulfate, sodium
laureth sulfate, and mixtures thereof.
32. An oral care composition according to claim 19 further
comprising an abrasive material, the abrasive material including a
small particle fraction comprising at least about 5 wt % of the
total composition weight, wherein the particles of the small
particle fraction have a d50 of less than 5 .mu.m.
33. An oral care composition according to claim 32 wherein the
small particle fraction comprising at least about 20 wt % of the
total composition weight.
34. An oral care composition according to claim 32 wherein the
abrasive material is selected from calcium carbonate, silica, and
mixtures thereof.
35. An oral care composition according to claim 32 wherein the
abrasive material comprises from 15 to 70 wt % of the total
composition weight.
36. Use of a basic amino acid, in free or salt form, in an oral
care composition comprising an anionic surfactant for reducing the
adhesion of bacteria to tooth surfaces in an oral cavity of a
subject.
37. Use according to claim 36 wherein the basic amino acid is
present in an amount of from 0.1 to 20 wt % of the total
composition weight.
38. Use according to claim 37 wherein the basic amino acid
comprises arginine.
39. Use according to claim 36 wherein the anionic surfactant is
present in an amount of from 0.01 to 10 wt % of the total
composition weight.
40. Use according to claim 39 wherein the anionic surfactant is
selected from sodium lauryl sulfate, sodium laureth sulfate, and
mixtures thereof.
41. Use of a basic amino acid, in free or salt form, for the
manufacture of a medicament which includes an anionic surfactant,
for use in reducing the adhesion of bacteria to tooth surfaces in
an oral cavity of a subject.
42. A method of reducing the adhesion of bacteria to tooth surfaces
in an oral cavity of a subject, the method comprising treating the
oral cavity with an oral care composition comprising a basic amino
acid, in free or salt form, and an anionic surfactant.
Description
[0001] This application claims the benefit of U.S. Ser. No.
61/027,432 filed Feb. 8, 2008, U.S. Ser. No. 61/027,431 filed Feb.
8, 2008 and U.S. Ser. No. 61/027,420 filed Feb. 8, 2008, the
contents of which are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] This invention relates to oral care compositions comprising
a basic amino acid in free or salt form, an anionic surfactant, and
optional additional agents, and to methods of using and of making
these compositions.
BACKGROUND OF THE INVENTION
[0003] Arginine and other basic amino acids have been proposed for
use in oral care and are believed to have benefits in combating
cavity formation and tooth sensitivity. Combining these basic amino
acids with minerals having oral care benefits, e.g., fluoride and
calcium, to form an oral care product having acceptable long term
stability, however, has proven challenging. In particular, the
basic amino acid may raise the pH and facilitate dissociation of
calcium ions that can react with fluoride ions to form an insoluble
precipitate. Moreover, the higher pH has the potential to cause
irritation. At neutral pH or acidic pH, however, a system utilizing
arginine bicarbonate (which the art teaches is preferred) may
release carbon dioxide, leading to bloating and bursting of the
containers. Moreover, it might be expected that lowering the pH to
neutral or acidic conditions would reduce the efficacy of the
formulation because the arginine may form an insoluble
arginine-calcium complex that has a poorer affinity for the tooth
surface, and moreover that lowering the pH would reduce any effect
the formulation might have on buffering cariogenic lactic acid in
the mouth. Partly because of these unaddressed formulation hurdles
and partly because arginine has generally been viewed in the art as
a potential alternative to fluoride rather than a co-active, there
has been little motivation to make oral care products comprising
both arginine and fluoride. Additional hurdles are potentially
posed by addition of an antimicrobial agent. Commercially available
arginine-based toothpaste, such as ProClude.RTM. and DenClude.RTM.,
for example, contain arginine bicarbonate and calcium carbonate,
but not fluoride nor any antimicrobial agent.
[0004] At the same time, the value of antimicrobial agents, such as
triclosan, in toothpaste has been recognized by many dentists.
These agents however are challenging to deliver in effective
amounts to the teeth and gums, and their solubility, delivery and
retention on the teeth is formulation dependent. For example,
triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is only slightly
soluble in water.
[0005] Accordingly, there is a need for a stable oral care product
that provides a basic amino acid, beneficial minerals such as
fluoride and calcium, improved activity against bacteria, and
improved delivery of antimicrobial agents.
BRIEF SUMMARY OF THE INVENTION
[0006] It is now surprisingly discovered that a basic amino acid
such as arginine in combination with an anionic surfactant can
reduce bacterial attachment and biofilm formation and additionally
dramatically enhance solubility, delivery, retention and
antibacterial effectiveness of an antibacterial agent such as
triclosan.
[0007] The invention thus encompasses oral care compositions and
methods of using the same that are effective in inhibiting or
reducing the accumulation of plaque, reducing levels of acid
producing (cariogenic) bacteria, remineralizing teeth, and
inhibiting or reducing gingivitis. The invention also encompasses
compositions and methods to clean the oral cavity and provide
improved methods of promoting oral health and/or systemic health,
including cardiovascular health, e.g., by reducing potential for
systemic infection via the oral tissues.
[0008] The invention thus comprises an oral care composition (a
Composition of the Invention), e.g., a dentifrice, comprising
i. an effective amount of a basic amino acid, in free or salt form,
e.g., arginine; ii. an effective amount of an anionic surfactant,
e.g., sodium lauryl sulfate; and an additional agent selected from
one or more of an antibacterial agent, e.g., a halogenated diphenyl
ether, e.g., triclosan; an effective amount of a fluoride source,
e.g., a soluble fluoride salt; and/or an anionic polymer, e.g., a
copolymer of methyl vinyl ether and maleic anhydride (PVM/MA). The
invention thus encompasses in one embodiment a toothpaste
comprising an arginine salt, e.g., arginine hydrochloride, arginine
phosphate or arginine bicarbonate; triclosan; an anionic
surfactant, e.g., sodium lauryl sulfate; a soluble fluoride salt,
e.g., sodium monofluorophosphate or sodium fluoride.
[0009] In one embodiment, the invention encompasses a Composition
of the Invention (Composition 1.1) further comprising a
particulate, the composition having a RDA of less than about 200,
e.g., less than about 160, e.g., about 40 to about 140, e.g.,
comprising at least about 5%. e.g., at least 20% of a particulate
having a d50 less than about 5 micrometers, e.g., silica having a
d50 of about 3 to about 4 micrometers or precipitated calcium
carbonate having a d50 of about 0.5 to about 3 micrometers.
[0010] In particular embodiments, the Compositions of the Invention
are in the form of a dentifrice comprising additional ingredients
selected from one or more of water, abrasives, surfactants, foaming
agents, vitamins, polymers, enzymes, humectants, thickeners,
antimicrobial agents, preservatives, flavorings, colorings and/or
combinations thereof.
[0011] Without intending to be bound by a particular theory, it is
hypothesized that a significant factor in the beneficial effect of
arginine is that arginine and other basic amino acids can be
metabolized by certain types of bacteria. e.g., S. sanguis which
are not cariogenic and which compete with cariogenic bacteria such
as S. mutans, for position on the teeth and in the oral cavity. The
arginolytic bacteria can use arginine and other basic amino acids
to produce ammonia, thereby raising the pH of their environment,
while cariogenic bacteria metabolize sugar to produce lactic acid,
which tends to lower the plaque pH and demineralize the teeth,
ultimately leading to cavities. It is believed that regular use of
a Composition of the Invention, over time, will lead to a relative
increase in the arginolytic bacteria and a relative decrease in the
cariogenic bacteria, resulting in a higher plaque pH, in effect
immunizing the teeth against cariogenic bacteria and their
detrimental effects. It is believed that this pH-raising effect may
be mechanistically separate from and complementary to the effect of
fluoride in promoting remineralization and strengthening the tooth
enamel.
[0012] Irrespective of the precise mechanism, however, it is
surprisingly found that the combination of fluoride and a basic
amino acid, e.g., arginine, in an oral care product according to
particular embodiments of the present invention produces unexpected
benefits beyond and qualitatively different from what can be
observed using compositions comprising effective amounts of either
compound separately, in promoting remineralization, repairing
pre-carious lesions, and enhancing oral health. It has moreover
been found that this action can be further enhanced by addition of
a small particle abrasive, which may act to help fill microtubules
in the dentin.
[0013] The presence of a basic amino acid in combination with an
anionic surfactant is also surprisingly found to reduce bacterial
adhesion to the tooth surface.
[0014] Of particular relevance to this invention, the basic amino
acid together with an anionic surfactant substantially enhances
solubilization, release, delivery, deposition, and effectiveness of
active agents, for example antimicrobial agents, such as
triclosan.
[0015] The reduction in bacterial adhesion and the improved
delivery and retention of an antibacterial agent, e.g., triclosan,
is further enhanced by the presence of an anionic polymer, e.g., a
polycarboxylate, e.g., PVM/MA. The invention thus further
encompasses methods to (i) reduce or inhibit formation of dental
caries, (ii) reduce, repair or inhibit early enamel lesions, e.g.,
as detected by quantitative light-induced fluorescence (QLF) or
electrical caries measurement (ECM), (iii) reduce or inhibit
demineralization and promote remineralization of the teeth, (iv)
reduce hypersensitivity of the teeth, (v) reduce or inhibit
gingivitis, (vi) promote healing of sores or cuts in the mouth,
(vii) reduce levels of acid producing bacteria, (viii) increase
relative levels of arginolytic bacteria, (ix) inhibit microbial
biofilm formation in the oral cavity, (x) raise and/or maintain
plaque pH at levels of at least pH 5.5 following sugar challenge,
(xi) reduce plaque accumulation, (xii) treat dry mouth; (xiii)
enhance systemic health, including cardiovascular health, e.g., by
reducing potential for systemic infection via the oral tissues,
(xiv) reduce erosion of the teeth, and/or (xv) clean and/or whiten
the teeth and clean the oral cavity, comprising applying a
Composition of the Invention to the oral cavity, e.g., by applying
a Composition of the Invention to the oral cavity of a patient in
need thereof.
DETAILED DESCRIPTION OF THE INVENTION
[0016] The invention thus comprises an oral care composition
(Composition 1.0) comprising
i. an effective amount of a basic amino acid, e.g., arginine, in
free or salt form; ii. an anionic surfactant, e.g., sodium lauryl
sulfate; and iii. an additional agent selected from one or more of
an effective amount of an active agents, e.g., an antimicrobial
agent, e.g., triclosan; an effective amount of a fluoride source,
e.g., a soluble fluoride salt; and/or an anionic polymer, e.g., a
copolymer of methyl vinyl ether and maleic anhydride; for example
any of the following compositions: 1.0.1. Composition 1.0 wherein
the basic amino acid is arginine, lysine, citrulline, ornithine,
creatine, histidine, diaminobutanoic acid, diaminoproprionic acid,
salts thereof and/or combinations thereof. 1.0.2. Composition 1.0
or 1.0.1 wherein the basic amino acid has the L-configuration.
1.0.3. Any of the preceding compositions is provided in the form of
a salt of a di- or tri-peptide comprising the basic amino acid.
1.0.4. Any of the preceding compositions wherein the basic amino
acid is arginine. 1.0.5. Any of the preceding compositions wherein
the basic amino acid is L-arginine. 1.0.6. Any of the preceding
compositions wherein the basic amino acid is partially or wholly in
salt form. 1.0.7. Composition 1.0.6 wherein the basic amino acid is
arginine phosphate. 1.0.8. Composition 1.0.6 wherein the basic
amino acid is in the form of arginine hydrochloride. 1.0.9.
Composition 1.0.6 wherein the basic amino acid is arginine sulfate.
1.0.10. Composition 1.0.6 wherein the basic amino acid is arginine
bicarbonate. 1.0.11. Any of the preceding compositions wherein a
salt of the basic amino acid is formed in situ in the formulation
by neutralization of the basic amino acid with an acid or a salt of
an acid. 1.0.12. Any of the preceding compositions wherein the salt
of the basic amino acid is formed by neutralization of the basic
amino acid to form a premix prior to combination with the fluoride
salt. 1.0.13. Any of the preceding compositions wherein the basic
amino acid is present in an amount corresponding to about 0.1 to
about 20%. e.g., about 1 wt % to about 10 wt %, for example about
3% to about 10% of the total composition weight, the weight of the
basic amino acid being calculated as free base form. 1.0.14.
Composition 1.0.11 wherein the basic amino acid is present in an
amount of about 7.5 wt % of the total composition weight. 1.0.15.
Composition 1.0.11 wherein the basic amino acid is present in an
amount of about 5 wt % of the total composition weight. 1.0.16.
Composition 1.0.11 wherein the basic amino acid is present in an
amount of about 3.75 wt % of the total composition weight. 1.0.17.
Composition 1.0.11 wherein the basic amino acid is present in an
amount of about 1.5 wt % of the total composition weight. 1.0.18.
Any of the preceding compositions wherein the fluoride salt is
stannous fluoride, sodium fluoride, potassium fluoride, sodium
monofluorophosphate, sodium fluorosilicate, ammonium
fluorosilicate, amine fluoride (e.g.
N'-octadecyltrimethylendiamine-N,N,N'-tris(2-ethanol)-dihydrofluoride),
ammonium fluoride, titanium fluoride, hexafluorosulfate, and
combinations thereof. 1.0.19. Any of the preceding compositions
wherein the fluoride salt is a fluorophosphate. 1.0.20. Any of the
preceding composition wherein the fluoride salt is sodium
monofluorophosphate. 1.0.21. Any of the preceding compositions
where the fluoride salt is sodium fluoride. 1.0.22. Any of the
preceding compositions wherein the fluoride salt is present in an
amount of about 0.01 wt. % to about 2 wt. % of the total
composition weight. 1.0.23. Any of the preceding compositions
wherein the fluoride salt provides fluoride ion in an amount of
about 0.1 to about 0.2 wt. % of the total composition weight.
1.0.24. Any of the preceding compositions wherein the soluble
fluoride salt provides fluoride ion in an amount of from about 50
to about 25,000 ppm. 1.0.25. Any of the preceding compositions
which is a mouthwash having 100 to about 250 ppm available fluoride
ion. 1.0.26. Any of the preceding compositions which is a
dentifrice having about 750 to about 2000 ppm available fluoride
ion. 1.0.27. Any of the preceding compositions wherein the
composition comprises about 750 to about 2000 ppm fluoride ion.
1.0.28. Any of the preceding compositions wherein the composition
comprises about 1000 to about 1500 ppm fluoride ion. 1.0.29. Any of
the preceding compositions wherein the composition comprises about
1450 ppm fluoride ion. 1.0.30. Any of the preceding compositions
wherein the pH is about 6 to about 9, e.g., about 6.5 to about 7.4
or about 7.5 to about 9. 1.0.31. Any of the preceding compositions
wherein the pH is about 6.5 to about 7.4. 1.0.32. Any of the
preceding compositions wherein the pH is about 6.8 to about 7.2.
1.0.33. Any of the preceding compositions wherein the pH is
approximately neutral. 1.0.34. Any of the preceding compositions
further comprising an abrasive or particulate. 1.0.35. The
immediately preceding composition wherein the abrasive or
particulate is selected from sodium bicarbonate, calcium phosphate
(e.g., dicalcium phosphate dihydrate), calcium sulfate, calcium
carbonate (e.g., precipitated calcium carbonate), silica (e.g.,
hydrated silica), iron oxide, hydroxyapatite, aluminum oxide,
perlite, plastic particles, e.g., polyethylene, and combinations
thereof. 1.0.36. The immediately preceding composition wherein the
abrasive or particulate is selected from a calcium phosphate (e.g.,
dicalcium phosphate dihydrate), calcium sulfate, precipitated
calcium carbonate, silica (e.g., hydrated silica), and combinations
thereof. 1.0.37. Any of the preceding compositions comprising an
abrasive in an amount of about 15 wt % to about 70 wt % of the
total composition weight. 1.0.38. Any of the preceding compositions
comprising a small particle abrasive fraction of at least about 5%
having a d50 of less than about 5 micrometers. 1.0.39. Any of the
preceding compositions having a RDA of less than 150, e.g., about
40 to about 140. 1.0.40. Any of the preceding compositions further
comprising an anti-calculus agent. 1.0.41. Any of the preceding
compositions further comprising an anti-calculus agent which is a
polyphosphate, e.g., pyrophosphate, tripolyphosphate, or
hexametaphosphate, e.g., in sodium salt form. 1.0.42. Any of the
preceding compositions wherein the anionic surfactant is selected
from a. water-soluble salts of higher fatty acid monoglyceride
monosulfates (e.g., the sodium salt of the monosulfated
monoglyceride of hydrogenated coconut oil fatty acids such as
sodium N-methyl N-cocoyl taurate sodium cocomo-glyceride sulfate),
b. higher alkyl sulfates, e.g., sodium lauryl sulfate. c. higher
alkyl-ether sulfates, e.g., of formula
CH.sub.3(CH.sub.2).sub.mCH.sub.2(OCH.sub.2CH.sub.2).sub.nOSO.sub.3X,
wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X is Na
or K (for example sodium laureth-2 sulfate
(CH.sub.3(CH.sub.2).sub.10CH.sub.2(OCH.sub.2CH.sub.2).sub.2OSO.sub.3Na)),
d. higher alkyl aryl sulfonates (such as sodium dodecyl benzene
sulfonate (sodium lauryl benzene sulfonate)), e. higher alkyl
sulfoacetates (such as sodium lauryl sulfoacetate (dodecyl sodium
sulfoacetate), higher fatty acid esters of 1,2 dihydroxy propane
sulfonate, sulfocolaurate (N-2-ethyl laurate potassium
sulfacetamide) and sodium lauryl sarcosinate), f. and mixtures
thereof. By "higher alkyl" is meant, e.g., C.sub.6-30 alkyl. In
particular embodiments, the anionic surfactant is selected from
sodium lauryl sulfate and sodium ether lauryl sulfate. 1.0.43. Any
of the preceding compositions wherein the anionic surfactant is
selected from sodium lauryl sulfate, sodium ether lauryl sulfate,
and mixtures thereof. 1.0.44. Any of the preceding compositions
wherein the anionic surfactant is present in an amount of from
about 0.3% to about 4.5% by weight. 1.0.45. Any of the preceding
compositions additionally comprising surfactants selected from
cationic, zwitterionic, and nonionic surfactants, and mixtures
thereof. 1.0.46. Any of the preceding compositions further
comprising at least one humectant. 1.0.47. Any of the preceding
compositions further comprising at least one humectant selected
from glycerin, sorbitol and combinations thereof. 1.0.48. Any of
the preceding compositions further comprising xylitol. 1.0.49. Any
of the preceding compositions further comprising at least one
polymer. 1.0.50. Any of the preceding compositions further
comprising at least one polymer selected from polyethylene glycols,
polyvinylmethyl ether maleic acid copolymers, polysaccharides
(e.g., cellulose derivatives, for example carboxymethyl cellulose,
or polysaccharide gums, for example xanthan gum or carrageenan
gum), and combinations thereof. 1.0.51. Any of the preceding
compositions further comprising gum strips or fragments. 1.0.52.
Any of the preceding compositions further comprising flavoring,
fragrance and/or coloring. 1.0.53. Any of the preceding
compositions further comprising water. 1.0.54. Any of the preceding
compositions further comprising an antibacterial agent selected
from halogenated diphenyl ether (e.g. triclosan), herbal extracts
and essential oils (e.g., rosemary extract, tea extract, magnolia
extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral,
hinokitol, catechol, methyl salicylate, epigallocatechin gallate,
epigallocatechin, gallic acid, miswak extract, sea-buckthorn
extract), bisguanide antiseptics (e.g., chlorhexidine, alexidine or
octenidene), quaternary ammonium compounds (e.g., cetylpyridinium
chloride (CPC), benzalkonium chloride, tetradecylpyridinium
chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC)),
phenolic antiseptics, hexetidine, octenidene, sanguinarine,
povidone iodine, delmopinol, salifluor, metal ions (e.g., zinc
salts, for example, zinc citrate, stannous salts, copper salts,
iron salts), sanguinarine, propolis and oxygenating agents (e.g.,
hydrogen peroxide, buffered sodium peroxyborate or
peroxycarbonate), phthalic acid and its salts, monoperthalic acid
and its salts and esters, ascorbyl stearate, oleoyl sarcosine,
alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphen
bromide, delmopinol, octapinol and other piperidino derivatives,
nicin preparations, chlorite salts; and mixtures of any of the
foregoing. 1.0.55. Any of the preceding compositions further
comprising an anti-inflammatory compound, e.g., an inhibitor of at
least one of host pro-inflammatory factors selected from matrix
metalloproteinases (MMP's), cyclooxygenases (COX), PGE.sub.2,
interleukin 1 (IL-1), IL-1.beta. converting enzyme (ICE),
transforming growth factor .beta.1 (TGF-.beta.1), inducible nitric
oxide synthase (iNOS), hyaluronidase, cathepsins, nuclear factor
kappa B (NF-.kappa.B), and IL-1 Receptor Associated Kinase (IRAK),
e.g., selected from aspirin, ketorolac, flurbiprofen, ibuprofen,
naproxen, indomethacin, aspirin, ketoprofen, piroxicam,
meclofenamic acid, nordihydroguairetic acid, and mixtures thereof.
1.0.56. Any of the preceding compositions further comprising an
antioxidant, e.g., selected from the group consisting of Co-enzyme
Q10, PQQ, Vitamin C. Vitamin E, Vitamin A, anethole-dithiothione,
and mixtures thereof. 1.0.57. Any of the preceding compositions
wherein the anti-bacterial is poorly soluble, e.g., no more soluble
than triclosan. 1.0.58. Any of the preceding compositions further
comprising triclosan. 1.0.59. Any of the preceding compositions
further comprising triclosan and xylitol. 1.0.60. Any of the
preceding compositions further comprising triclosan, xylitol, and
precipitated calcium carbonate. 1.0.61. Any of the preceding
compositions further comprising triclosan and a Zn.sup.2+ ion
source (e.g., zinc citrate). 1.0.62. Any of the preceding
compositions further comprising an antibacterial agent in an amount
of about 0.01 to about 5 wt. % of the total composition weight.
1.0.63. Any of the preceding compositions further comprising
triclosan in an amount of about 0.01 to about 1 wt. % of the total
composition weight. 1.0.64. Any of the preceding compositions
further comprising triclosan in an amount of about 0.3% of the
total composition weight. 1.0.65. Any of the preceding compositions
further comprising triclosan and a Zn.sup.2+ ion source e.g., zinc
citrate. 1.0.66. Any of the preceding compositions further
comprising a whitening agent. 1.0.67. Any of the preceding
compositions further comprising a whitening agent selected from a
whitening active selected from the group consisting of peroxides,
metal chlorites, perborates, percarbonates, peroxyacids,
hypochlorites, and combinations thereof. 1.0.68. Any of the
preceding compositions further comprising hydrogen peroxide or a
hydrogen peroxide source, e.g., urea peroxide or a peroxide salt or
complex (e.g., such as peroxyphosphate, peroxycarbonate, perborate,
peroxysilicate, or persulphate salts; for example calcium
peroxyphosphate, sodium perborate, sodium carbonate peroxide,
sodium peroxyphosphate, and potassium persulfate), or hydrogen
peroxide polymer complexes such as hydrogen peroxide-polyvinyl
pyrrolidone polymer complexes. 1.0.69. Any of the preceding
compositions further comprising an agent that interferes with or
prevents bacterial attachment, e.g., solbrol or chitosan. 1.0.70.
Any of the preceding compositions further comprising a source of
calcium and phosphate selected from (i) calcium-glass complexes
e.g., calcium sodium phosphosilicates, and (ii) calcium-protein
complexes, e.g., casein phosphopeptide-amorphous calcium phosphate.
1.0.71. Any of the preceding compositions further comprising a
soluble calcium salt, e.g., selected from calcium sulfate, calcium
chloride, calcium nitrate, calcium acetate, calcium lactate, and
combinations thereof. 1.0.72. Any of the preceding compositions
further comprising a physiologically acceptable potassium salt,
e.g., potassium nitrate or potassium chloride, in an amount
effective to reduce dentinal sensitivity. 1.0.73. Any of the
preceding compositions further comprising from about 0.1% to about
7.5% of a physiologically acceptable potassium salt, e.g.,
potassium nitrate and/or potassium chloride. 1.0.74. Any of the
preceding compositions which is a toothpaste comprising an arginine
salt, e.g., arginine hydrochloride, arginine phosphate or arginine
bicarbonate; triclosan; an anionic surfactant, e.g., sodium lauryl
sulfate; and a soluble fluoride salt, e.g., sodium
monofluorophosphate or sodium fluoride. 1.0.75. Any of the
preceding compositions effective upon application to the oral
cavity, e.g., with brushing, to (i) reduce or inhibit formation of
dental caries, (ii) reduce, repair or inhibit pre-carious lesions
of the enamel, e.g., as detected by quantitative light-induced
fluorescence (QLF) or electrical caries measurement (ECM), (iii)
reduce or inhibit demineralization and promote remineralization of
the teeth, (iv) reduce hypersensitivity of the teeth, (v) reduce or
inhibit gingivitis, (vi) promote healing of sores or cuts in the
mouth, (vii) reduce levels of acid producing bacteria, (viii) to
increase relative levels of arginolytic bacteria, (ix) inhibit
microbial biofilm formation in the oral cavity, (x) raise and/or
maintain plaque pH at levels of at least pH 5.5 following sugar
challenge, (xi) reduce plaque accumulation, (xii) treat, relieve or
reduce dry mouth, (xiii) clean the teeth and oral cavity (xiv)
reduce erosion, (xv) whiten teeth, (xvi) immunize the teeth against
cariogenic bacteria; and/or (xvii) promote systemic health,
including cardiovascular health, e.g., by reducing potential for
systemic infection via the oral tissues. 1.0.76. A composition
obtained or obtainable by combining the ingredients as set forth in
any of the preceding compositions. 1.0.77. Any of the preceding
compositions in a form selected from mouth rinse, toothpaste, tooth
gel, tooth powder, non-abrasive gel, mousse, foam, mouth spray,
lozenge, oral tablet, dental implement, and pet care product.
1.0.78. Any of the preceding compositions wherein the composition
is toothpaste. 1.0.79. Any of the preceding compositions wherein
the composition is a toothpaste optionally further comprising one
or more of one or more of water, abrasives, surfactants, foaming
agents, vitamins, polymers, enzymes, humectants, thickeners,
antimicrobial agents, preservatives, flavorings, colorings and/or
combinations thereof. 1.0.80. Any of the preceding compositions
1.0-1.0.78 wherein the composition is a mouthwash. 1.0.81. Any of
the preceding compositions further comprising a breath freshener,
fragrance or flavoring.
[0017] In another embodiment, the invention encompasses a
Composition of the Invention (Composition 1.1) e.g., according to
any of the preceding Compositions 1.0-1.0.81, comprising
i. an effective amount of a salt of a basic amino acid; ii. an
effective amount of a soluble fluoride salt; iii. an anionic
surfactant, e.g., sodium lauryl sulfate; iv. an anionic polymer,
e.g., a copolymer of methyl vinyl ether and maleic anhydride; and
v. an antibacterial agent, e.g., triclosan.
[0018] In another embodiment, the invention encompasses a
Composition of the Invention (Composition 1.2) e.g., according to
any of the preceding Compositions 1.0-1.0.81, comprising
i. an effective amount of a salt of a basic amino acid; ii. an
antibacterial agent, e.g. triclosan; iii. an effective amount of a
soluble fluoride salt; and iv. small particle abrasive, such that
the composition has a RDA of less than about 160, e.g., about 40 to
about 140, e.g. comprising at least about 5%, e.g., at least about
20% of an abrasive having a d50 less than about 5 micrometers,
e.g., silica having a d50 of about 3 to about 4 micrometers.
[0019] In another embodiment, the invention encompasses a method
(Method 2) to improve oral health comprising applying an effective
amount of the oral composition of any of the embodiments under
Compositions 1.0, 1.1, or 1.2, to the oral cavity of a subject in
need thereof, e.g., a method to
i. reduce or inhibit formation of dental caries, ii. reduce, repair
or inhibit early enamel lesions, e.g., as detected by quantitative
light-induced fluorescence (QLF) or electrical caries measurement
(ECM), iii. reduce or inhibit demineralization and promote
remineralization of the teeth, iv. reduce hypersensitivity of the
teeth, v. reduce or inhibit gingivitis, vi. promote healing of
sores or cuts in the mouth, vii. reduce levels of acid producing
bacteria, viii. to increase relative levels of arginolytic
bacteria, ix. inhibit microbial biofilm formation in the oral
cavity, x. raise and/or maintain plaque pH at levels of at least
about pH 5.5 following sugar challenge, xi. reduce plaque
accumulation, xii. treat dry mouth, xiii. enhance systemic health,
including cardiovascular health, e.g., by reducing potential for
systemic infection via the oral tissues, xiv. whiten teeth, xv. to
reduce erosion of the teeth, xvi. immunize the teeth against
cariogenic bacteria, and/or xvii. clean the teeth and oral
cavity.
[0020] The invention further comprises the use of arginine in the
manufacture of a Composition of the Invention, e.g., for use in any
of the indications set forth in Method 2.
[0021] The invention further provides an oral care composition
comprising a basic amino acid, in free or salt form, and an anionic
surfactant for reducing the adhesion of bacteria to tooth surfaces
in an oral cavity of a subject.
[0022] The invention further provides the use of a basic amino
acid, in free or salt form, in an oral care composition comprising
an anionic surfactant for reducing the adhesion of bacteria to
tooth surfaces in an oral cavity of a subject.
[0023] The invention further provides the use of a basic amino
acid, in free or salt form, for the manufacture of a medicament
which includes an anionic surfactant, for use in reducing the
adhesion of bacteria to tooth surfaces in an oral cavity of a
subject.
[0024] The invention further provides a method of reducing the
adhesion of bacteria to tooth surfaces in an oral cavity of a
subject, the method comprising treating the oral cavity with an
oral care composition comprising a basic amino acid, in free or
salt form, and an anionic surfactant.
[0025] It may therefore be seen by the skilled practitioner in the
oral care art that a surprising technical effect and advantage of
reduced bacterial adhesion to the teeth can result from the
formulation, and use, of an oral care composition, for example a
dentifrice, in accordance with one or more aspects of the
invention, which are directed to the provision of combinations of
active components or ingredients, and preferably their respective
amounts, within the composition.
[0026] Levels of active ingredients will vary based on the nature
of the delivery system and the particular active. For example, the
basic amino acid may be present at levels from, e.g., about 0.1 to
about 20 wt % (expressed as weight of free base), e.g., about 0.1
to about 3 wt % for a mouth rinse, about 1 to about 10 wt % for a
consumer toothpaste or about 7 to about 20 wt % for a professional
or prescription treatment product. Fluoride may be present at
levels of, e.g., about 25 to about 25,000 ppm, for example about 25
to about 250 ppm for a mouth rinse, about 750 to about 2,000 ppm
for a consumer toothpaste, or about 2,000 to about 25,000 ppm for a
professional or prescription treatment product. Levels of
antibacterial will vary similarly, with levels used in toothpaste
being e.g., about 5 to about 15 times greater than used in mouth
rinse. For example, a triclosan mouth rinse may contain, e.g.,
about 0.03 wt % triclosan while a triclosan toothpaste may contain,
e.g., about 0.3 wt % triclosan.
Basic Amino Acids
[0027] The basic amino acids which can be used in the compositions
and methods of the invention include not only naturally occurring
basic amino acids, such as arginine, lysine, and histidine, but
also any basic amino acids having a carboxyl group and an amino
group in the molecule, which are water-soluble and provide an
aqueous solution with a pH of about 7 or greater.
[0028] Accordingly, basic amino acids include, but are not limited
to, arginine, lysine, citrulline, ornithine, creatine histidine,
diaminobutanoic acid, diaminoproprionic acid, salts thereof or
combinations thereof. In a particular embodiment, the basic amino
acids are selected from arginine, citrulline, and ornithine.
[0029] In certain embodiments, the basic amino acid is arginine,
for example, l-arginine, or a salt thereof.
[0030] In some embodiments the basic amino acid comprises at least
one intermediate produced in the arginine deiminase system. The
intermediates produced in the arginine deiminase system may be
useful in an oral care composition to provide plaque neutralization
for caries control and/or prevention. Arginine is a natural basic
amino acid that may be found in the oral cavity. Arginine in the
mouth may be utilized by certain dental plaque bacterial strains
such as S. sanguis, S. gordonii, S. parasanguis, S. rattus, S.
milleri, S. anginosus, S. faecalis, A. naeslundii, A. odonolyticus,
L. cellobiosus, L. brevis, L. fermentum, P. gingivalis, and T.
denticola for their survival. Such organisms may perish in an
acidic environment that may be present at areas close to the tooth
surface where acidogenic and aciduric cariogenic strains may use
sugars to produce organic acids. Thus, these arginolytic strains
may break down arginine to ammonia to provide alkalinity to survive
and, in addition, buffer the plaque and make a hostile environment
for the cariogenic systems.
[0031] Such arginolytic organisms may catabolize arginine by an
internal cellular enzyme pathway system called the "arginine
deiminase system" whereby intermediates in the pathway are formed.
In this pathway, L-arginine may be broken down to L-citrulline and
ammonia by arginine deiminase. L-citrulline may then be broken down
by ornithane transcarbamylase in the presence of inorganic
phosphate to L-ornithine and carbamyl phosphate. Carbamate kinase
may then break down carbamyl phosphate to form another molecule of
ammonia and carbon dioxide, and in the process also forms ATP
(adenosine 5'-triphosphate). ATP may be used by the arginolytic
bacteria as an energy source for growth. Accordingly, when
utilized, the arginine deiminase system may yield two molecules of
ammonia.
[0032] It has been found that, in some embodiments, the ammonia may
help in neutralizing oral plaque pH to control and/or prevent
dental caries.
[0033] The oral care composition of some embodiments of the present
invention may include intermediates produced in the arginine
deiminase system. Such intermediates may include citrulline,
ornithine, and carbamyl phosphate. In some embodiments, the other
care composition includes citrulline. In some embodiments, the oral
care composition includes ornithine. In some embodiments, the oral
care composition includes carbamyl phosphate. In other embodiments,
the oral care composition includes any combination of citrulline,
ornithine, carbamyl phosphate, and/or other intermediates produced
by the arginine deiminase system.
[0034] The oral care composition may include the above described
intermediates in an effective amount. In some embodiments, the oral
care composition includes about 1 mmol/L to about 10 mmol/L
intermediate. In other embodiments, the oral care composition
includes about 3 mmol/L to about 7 mmol/L intermediate. In other
embodiments, the oral care composition includes about 5 mmol/L
intermediate.
[0035] The compositions of the invention are intended for topical
use in the mouth and so salts for use in the present invention
should be safe for such use, in the amounts and concentrations
provided. Suitable salts include salts known in the art to be
pharmaceutically acceptable salts are generally considered to be
physiologically acceptable in the amounts and concentrations
provided. Physiologically acceptable salts include those derived
from pharmaceutically acceptable inorganic or organic acids or
bases, for example acid addition salts formed by acids which form a
physiological acceptable anion, e.g., hydrochloride or bromide
salt, and base addition salts formed by bases which form a
physiologically acceptable cation, for example those derived from
alkali metals such as potassium and sodium or alkaline earth metals
such as calcium and magnesium. Physiologically acceptable salts may
be obtained using standard procedures known in the art, for
example, by reacting a sufficiently basic compound such as an amine
with a suitable acid affording a physiologically acceptable
anion.
[0036] In various embodiments, the basic amino acid is present in
an amount of about 0.5 wt. % to about 20 wt. % of the total
composition weight, about 1 wt. % to about 10 wt. % of the total
composition weight, for example about 1.5 wt. %, 3.75 wt. %, 5 wt.
%, or 7.5 wt. % of the total composition weight.
[0037] RDA: RDA is an abbreviation for radioactive dentin abrasion,
a relative measure of abrasivity. Typically, extracted human or cow
teeth are irradiated in a neutron flux, mounted in
methylmethacrylate (bone glue), stripped of enamel, inserted into a
brushing-machine, brushed by American Dental Association (ADA)
standards (reference toothbrush, 150 g pressure, 1500 strokes,
4-to-1 water-toothpaste slurry). The radioactivity of the rinse
water is then measured and recorded. For experimental control, the
test is repeated with an ADA reference toothpaste made of calcium
pyrophosphate, with this measurement given a value of 100 to
calibrate the relative scale.
Fluoride Ion Source
[0038] The oral care compositions may further include one or more
fluoride ion sources, e.g., soluble fluoride salts. A wide variety
of fluoride ion-yielding materials can be employed as sources of
soluble fluoride in the present compositions. Examples of suitable
fluoride ion-yielding materials are found in U.S. Pat. No.
3,535,421, to Briner et al.; U.S. Pat. No. 4,885,155, to Parran,
Jr. et al. and U.S. Pat. No. 3,678,154, to Widder et al.,
incorporated herein by reference.
[0039] Representative fluoride ion sources include, but are not
limited to, stannous fluoride, sodium fluoride, potassium fluoride,
sodium monofluorophosphate, sodium fluorosilicate, ammonium
fluorosilicate, amine fluoride, ammonium fluoride, and combinations
thereof. In certain embodiments the fluoride ion source includes
stannous fluoride, sodium fluoride, sodium monofluorophosphate as
well as mixtures thereof.
[0040] In certain embodiments, the oral care composition of the
invention may also contain a source of fluoride ions or
fluorine-providing ingredient in amounts sufficient to supply about
25 ppm to about 25,000 ppm of fluoride ions, generally at least
about 500 ppm, e.g., 500 to 2000 ppm, e.g., 1000-1600 ppm, e.g.,
about 1450 ppm. The appropriate level of fluoride will depend on
the particular application. A mouthwash, for example, would
typically have 100-250 ppm fluoride. A toothpaste for general
consumer use would typically have 1000-1500 ppm, with pediatric
toothpaste having somewhat less. A dentifrice or coating for
professional application could have as much as about 5,000 or even
about 25.000 ppm fluoride.
[0041] Fluoride ion sources may be added to the compositions of the
invention at a level of about 0.01 wt. % to about 10 wt. % in one
embodiment or about 0.03 wt. % to about 5 wt. %, and in another
embodiment about 0.1 wt. % to about 1 wt. % by weight of the
composition in another embodiment. Weights of fluoride salts to
provide the appropriate level of fluoride ion will obviously vary
based on the weight of the counter ion in the salt.
Abrasives
[0042] The Compositions of the Invention may comprise a calcium
phosphate abrasive, e.g., tricalcium phosphate
(Ca.sub.3(PO.sub.4).sub.2), hydroxyapatite
(Ca.sub.10(PO.sub.4).sub.6(OH).sub.2), dicalcium phosphate
dihydrate (CaHPO.sub.42H.sub.2O, also sometimes referred to herein
as DiCal), or calcium pyrophosphate. Alternatively, calcium
carbonate, and in particular precipitated calcium carbonate, may be
employed as an abrasive.
[0043] The compositions may include one or more additional
abrasives, for example silica abrasives such as precipitated
silicas having a mean particle size of up to about 20 microns, such
as Zeodent 115.RTM., marketed by J. M. Huber. Other useful
abrasives also include sodium metaphosphate, potassium
metaphosphate, aluminum silicate, calcined alumina, bentonite or
other siliceous materials, or combinations thereof.
[0044] The silica abrasive polishing materials useful herein, as
well as the other abrasives, generally have an average particle
size ranging about 0.1-about 30 microns, about 5-about 15 microns.
The silica abrasives can be from precipitated silica or silica
gels, such as the silica xerogels described in U.S. Pat. No.
3,538,230, to Pader et al. and U.S. Pat. No. 3,862,307, to
Digiulio, both incorporated herein by reference. Particular silica
xerogels are marketed under the trade name Syloid.RTM. by the W. R.
Grace & Co., Davison Chemical Division. The precipitated silica
materials include those marketed by the J. M. Huber Corp. under the
trade name Zeodent.RTM., including the silica carrying the
designation Zeodent 115 and 119. These silica abrasives are
described in U.S. Pat. No. 4,340,583, to Wason, incorporated herein
by reference.
[0045] In certain embodiments, abrasive materials useful in the
practice of the oral care compositions in accordance with the
invention include silica gels and precipitated amorphous silica
having an oil absorption value of about less than about 100 cc/100
g silica and in the range of about 45 cc/100 g to about 70 cc/100 g
silica. Oil absorption values are measured using the ASTM Rub-Out
Method D281. In certain embodiments, the silicas are colloidal
particles having an average particle size of about 3 microns to
about 12 microns, and about 5 to about 10 microns.
[0046] In particular embodiments, the abrasive materials comprise a
large fraction of very small particles, e.g., having a d50 less
than about 5 microns. For example small particle silica (SPS)
having a d50 of about 3-about 4 microns, for example Sorbosil
AC43.RTM. (Ineos). Such small particles are particularly useful in
formulations targeted at reducing hypersensitivity. The small
particle component may be present in combination with a second
larger particle abrasive. In certain embodiments, for example, the
formulation comprises about 3 to about 8% small particle abrasive
e.g., small particle silica and about 10 to about 45% of a
conventional abrasive.
[0047] Low oil absorption silica abrasives particularly useful in
the practice of the invention are marketed under the trade
designation Sylodent XWA.RTM. by Davison Chemical Division of W.R.
Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA.RTM., a
silica hydrogel composed of particles of colloidal silica having a
water content of about 29% by weight averaging about 7 to about 10
microns in diameter, and an oil absorption of less than about 70
cc/100 g of silica is an example of a low oil absorption silica
abrasive useful in the practice of the present invention. The
abrasive is present in the oral care composition of the present
invention at a concentration of about 10 to about 60% by weight, in
other embodiment about 20 to about 45% by weight, and in another
embodiment about 30 to about 50% by weight.
[0048] In some embodiments the basic amino acid is incorporated
into a dentifrice composition having a base formulation comprising
calcium carbonate, and in particular precipitated calcium
carbonate, as an abrasive. L-arginine and arginine salts such as
arginine bicarbonate are themselves distinctly bitter in taste, and
in aqueous solution can also impart a fishy taste. Consequently, it
was expected that when L-arginine or arginine salts were
incorporated into oral care products such as dentifrice
formulations at effective concentrations to impart anticavity
efficacy and sensitivity relief, typically in an amount of from 2
to 10 wt % based on the total weight of the dentifrice formulation,
the taste and mouthfeel of the dentifrice formulations would be
degraded as compared to the same formulation without the addition
of L-arginine or arginine salts.
[0049] However, it has surprisingly been found in accordance with
this aspect of the present invention that the addition of
L-arginine or arginine salts to a base dentifrice formulation
comprising calcium carbonate can provide a significant enhancement
of taste and mouthfeel attributes to the dentifrice formulation and
to an increase in the overall acceptance of the product to a
consumer.
Agents to Increase the Amount of Foaming
[0050] The oral care compositions of the invention also may include
an agent to increase the amount of foam that is produced when the
oral cavity is brushed.
[0051] Illustrative examples of agents that increase the amount of
foam include, but are not limited to polyoxyethylene and certain
polymers including, but not limited to, alginate polymers.
[0052] The polyoxyethylene may increase the amount of foam and the
thickness of the foam generated by the oral care carrier component
of the present invention. Polyoxyethylene is also commonly known as
polyethylene glycol ("PEG") or polyethylene oxide. The
polyoxyethylenes suitable for this invention will have a molecular
weight of about 200,000 to about 7,000,000. In one embodiment the
molecular weight will be about 600,000 to about 2,000,000 and in
another embodiment about 800,000 to about 1,000,000. Polyox.RTM. is
the trade name for the high molecular weight polyoxyethylene
produced by Union Carbide.
[0053] The polyoxyethylene may be present in an amount of about 1%
to about 90%, in one embodiment about 5% to about 50% and in
another embodiment about 10% to about 20% by weight of the oral
care carrier component of the oral care compositions of the present
invention. The dosage of foaming agent in the oral care composition
(i.e., a single dose) is about 0.01 to about 0.9% by weight, about
0.05 to about 0.5% by weight, and in another embodiment about 0.1
to about 0.2% by weight.
Surfactants
[0054] The invention contains anionic surfactants, for example
i. water-soluble salts of higher fatty acid monoglyceride
monosulfates, such as the sodium salt of the monosulfated
monoglyceride of hydrogenated coconut oil fatty acids such as
sodium N-methyl N-cocoyl taurate, sodium cocomo-glyceride sulfate,
ii. higher alkyl sulfates, such as sodium lauryl sulfate, iii.
higher alkyl-ether sulfates. e.g., of formula
CH.sub.3(CH.sub.2).sub.mCH.sub.2(OCH.sub.2CH.sub.2).sub.nOSO.sub.3X,
wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X is Na
or K, for example sodium laureth-2 sulfate
(CH.sub.3(CH.sub.2).sub.10CH.sub.2(OCH.sub.2CH.sub.2).sub.2OSO.sub.3Na).
iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene
sulfonate (sodium lauryl benzene sulfonate) v. higher alkyl
sulfoacetates, such as sodium lauryl sulfoacetate (dodecyl sodium
sulfoacetate), higher fatty acid esters of 1,2 dihydroxy propane
sulfonate, sulfocolaurate (N-2-ethyl laurate potassium
sulfacetamide) and sodium lauryl sarcosinate. By "higher alkyl" is
meant, e.g., C.sub.6-30 alkyl. In particular embodiments, the
anionic surfactant is selected from sodium lauryl sulfate and
sodium ether lauryl sulfate.
[0055] The anionic surfactant is present in an amount which is
effective, e.g., greater than about 0.01% by weight of the
formulation, but not at a concentration which would be irritating
to the oral tissues e.g., less than about 10%, and optimal
concentrations depend on the particular formulation and the
particular surfactant. For example, concentrations used or a
mouthwash are typically on the order of one tenth that used for a
toothpaste. In one embodiment, the anionic surfactant is present in
a toothpaste at from about 0.3% to about 4.5% by weight, e.g.,
about 1.5%.
[0056] The Compositions of the Invention may optionally contain
mixtures of surfactants, comprising anionic surfactants and other
surfactants which may be anionic, cationic, zwitterionic or
nonionic. Generally, surfactants are those which are reasonably
stable throughout a wide pH range. Surfactants are described more
fully, for example, in U.S. Pat. No. 3,959,458, to Agricola et al.;
U.S. Pat. No. 3,937,807, to Haefele; and U.S. Pat. No. 4,051,234,
to Gieske et al., which are incorporated herein by reference.
[0057] In certain embodiments, the anionic surfactants useful
herein include the water-soluble salts of alkyl sulfates having
about 10 to about 18 carbon atoms in the alkyl radical and the
water-soluble salts of sulfonated monoglycerides of fatty acids
having about 10 to about 18 carbon atoms. Sodium lauryl sulfate,
sodium lauroyl sarcosinate and sodium coconut monoglyceride
sulfonates are examples of anionic surfactants of this type.
Mixtures of anionic surfactants may also be utilized.
[0058] In another embodiment, cationic surfactants useful in the
present invention can be broadly defined as derivatives of
aliphatic quaternary ammonium compounds having one long alkyl chain
containing about 8 to about 18 carbon atoms such as lauryl
trimethylammonium chloride, cetyl pyridinium chloride, cetyl
trimethylammonium bromide,
di-isobutylphenoxyethyldimethylbenzylammonium chloride coconut
alkyltrimethylammonium nitrite, cetyl pyridinium fluoride, and
mixtures thereof.
[0059] Illustrative cationic surfactants are the quaternary
ammonium fluorides described in U.S. Pat. No. 3,535,421, to Briner
et al., herein incorporated by reference. Certain cationic
surfactants can also act as germicides in the compositions.
[0060] Illustrative nonionic surfactants that can be used in the
compositions of the invention can be broadly defined as compounds
produced by the condensation of alkylene oxide groups (hydrophilic
in nature) with an organic hydrophobic compound which may be
aliphatic or alkylaromatic in nature. Examples of suitable nonionic
surfactants include, but are not limited to, the Pluronics,
polyethylene oxide condensates of alkyl phenols, products derived
from the condensation of ethylene oxide with the reaction product
of propylene oxide and ethylene diamine, ethylene oxide condensates
of aliphatic alcohols, long chain tertiary amine oxides, long chain
tertiary phosphine oxides, long chain dialkyl sulfoxides and
mixtures of such materials.
[0061] In certain embodiments, zwitterionic synthetic surfactants
useful in the present invention can be broadly described as
derivatives of aliphatic quaternary ammonium, phosphonium, and
sulfonium compounds in which the aliphatic radicals can be straight
chain or branched, and wherein one of the aliphatic substituents
contains about 8 to about 18 carbon atoms and one contains an
anionic water-solubilizing group, e.g., carboxy, sulfonate,
sulfate, phosphate or phosphonate. Illustrative examples of the
surfactants suited for inclusion into the composition include, but
are not limited to, sodium alkyl sulfate, sodium lauroyl
sarcosinate, cocoamidopropyl betaine and polysorbate 20, and
combinations thereof.
[0062] In a particular embodiment, the Composition of the Invention
comprises sodium lauryl sulfate.
[0063] The surfactant or mixtures of compatible surfactants can be
present in the compositions of the present invention in about 0.1%
to about 5%, in another embodiment about 0.3% to about 3% and in
another embodiment about 0.5% to about 2% by weight of the total
composition.
Flavoring Agents
[0064] The oral care compositions of the invention may also include
a flavoring agent. Flavoring agents which are used in the practice
of the present invention include, but are not limited to essential
oils as well as various flavoring aldehydes, esters, alcohols, and
similar materials. Examples of the essential oils include oils of
spearmint, peppermint, wintergreen, sassafras, clove, sage,
eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and
orange. Also useful are such chemicals as menthol, carvone, and
anethole. Certain embodiments employ the oils of peppermint and
spearmint.
[0065] The flavoring agent is incorporated in the oral composition
at a concentration of about 0.1 to about 5% by weight and about 0.5
to about 1.5% by weight. The dosage of flavoring agent in the
individual oral care composition dosage (i.e., a single dose) is
about 0.001 to 0.05% by weight and in another embodiment about
0.005 to 0.015% by weight.
Chelating Agents
[0066] The oral care compositions of the invention also may
optionally include one or more chelating agents able to complex
calcium found in the cell walls of the bacteria. Binding of this
calcium weakens the bacterial cell wall and augments bacterial
lysis.
[0067] Another group of agents suitable for use as chelating agents
in the present invention are the soluble pyrophosphates. The
pyrophosphate salts used in the present compositions can be any of
the alkali metal pyrophosphate salts. In certain embodiments, salts
include tetra alkali metal pyrophosphate, dialkali metal diacid
pyrophosphate, trialkali metal monoacid pyrophosphate and mixtures
thereof wherein the alkali metals are sodium or potassium. The
salts are useful in both their hydrated and unhydrated forms. An
effective amount of pyrophosphate salt useful in the present
composition is generally enough to provide at least about 1 wt. %
pyrophosphate ions, about 1.5 wt. % to about 6 wt. %, about 3.5 wt.
% to about 6 wt. % of such ions.
Polymers
[0068] The oral care compositions of the invention also optionally
include one or more polymers, such as polyethylene glycols,
polyvinylmethyl ether maleic acid copolymers, polysaccharides
(e.g., cellulose derivatives, for example carboxymethyl cellulose,
or polysaccharide gums, for example xanthan gum or carrageenan
gum). Acidic polymers, for example polyacrylate gels, may be
provided in the form of their free acids or partially or fully
neutralized water soluble alkali metal (e.g., potassium and sodium)
or ammonium salts.
[0069] Particularly when noncationic antibacterial agents or
antibacterial agents, e.g., triclosan, are included in any of the
dentifrice components, there is also preferably included from about
0.05 to about 5% of an agent which enhances the deliver, and
retention of the agents to, and retention thereof on oral surfaces.
Such agents useful in the present invention are disclosed in U.S.
Pat. Nos. 5,188,821 and 5,192,531; and include synthetic anionic
polymeric polycarboxylates, such as about 1:4 to about 4:1
copolymers of maleic anhydride or acid with another polymerizable
ethylenically unsaturated monomer, preferably methyl vinyl
ether/maleic anhydride having a molecular weight (M.W.) of about
30,000 to about 1,000,000, most preferably about 30,000 to about
800,000. These copolymers are available for example as Gantrez,
e.g. AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably
S-97 Pharmaceutical Grade (M.W. 700,000) available from ISP
Technologies. Inc. Bound Brook, N.J. 08805. The enhancing agents
when present are present in amounts ranging from about 0.05 to
about 3% by weight.
[0070] Other operative polymers include those such as the 1:1
copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl
methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being
available for example as Monsanto EMA No. 1103, M.W. 10,000 and EMA
Grade 61, and 1:1 copolymers of acrylic acid with methyl or
hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl
ether or N-vinyl-2-pyrrolidone.
[0071] Suitable generally, are polymerized olefinically or
ethylenically unsaturated carboxylic acids containing an activated
carbon-to-carbon olefinic double bond and at least one carboxyl
group, that is, an acid containing an olefinic double bond which
readily functions in polymerization because of its presence in the
monomer molecule either in the alpha-beta position with respect to
a carboxyl group or as part of a terminal methylene grouping.
Illustrative of such acids are acrylic, methacrylic, ethacrylic,
alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic,
alpha-chlorsorbic, cinnamic, beta-styrylacrylic, muconic, itaconic,
citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic,
2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric,
maleic acids and anhydrides. Other different olefinic monomers
copolymerizable with such carboxylic monomers include vinylacetate,
vinyl chloride, dimethyl maleate and the like. Copolymers contain
sufficient carboxylic salt groups for water-solubility.
[0072] A further class of polymeric agents includes a composition
containing homopolymers of substituted acrylamides and/or
homopolymers of unsaturated sulfonic acids and salts thereof, in
particular where polymers are based on unsaturated sulfonic acids
selected from acrylamidoalykane sulfonic acids such as 2-acrylamide
2 methylpropane sulfonic acid having a molecular weight of about
1,000 to about 2,000,000, described in U.S. Pat. No. 4,842,847,
Jun. 27, 1989 to Zahid, incorporated herein by reference.
[0073] Another useful class of polymeric agents includes polyamino
acids, particularly those containing proportions of anionic
surface-active amino acids such as aspartic acid, glutamic acid and
phosphoserine, as disclosed in U.S. Pat. No. 4,866,161 Sikes et
al., incorporated herein by reference.
[0074] In preparing oral care compositions, it is sometimes
necessary to add some thickening material to provide a desirable
consistency or to stabilize or enhance the performance of the
formulation. In certain embodiments, the thickening agents are
carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose and
water soluble salts of cellulose ethers such as sodium
carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl
cellulose. Natural gums such as karaya, gum arabic, and gum
tragacanth can also be incorporated. Colloidal magnesium aluminum
silicate or finely divided silica can be used as component of the
thickening composition to further improve the composition's
texture. In certain embodiments, thickening agents in an amount of
about 0.5% to about 5.0% by weight of the total composition are
used.
Enzymes
[0075] The oral care compositions of the invention may also
optionally include one or more enzymes. Useful enzymes include any
of the available proteases, glucanohydrolases, endoglycosidases,
amylases, mutanases, lipases and mucinases or compatible mixtures
thereof. In certain embodiments, the enzyme is a protease,
dextrinase, endoglycosidase and mutanase. In another embodiment,
the enzyme is papain, endoglycosidase or a mixture of dextrinase
and mutanase. Additional enzymes suitable for use in the present
invention are disclosed in U.S. Pat. No. 5,000,939 to Dring et al.,
U.S. Pat. No. 4,992,420; U.S. Pat. No. 4,355,022; U.S. Pat. No.
4,154,815; U.S. Pat. No. 4,058,595; U.S. Pat. No. 3,991,177; and
U.S. Pat. No. 3,696,191 all incorporated herein by reference. An
enzyme of a mixture of several compatible enzymes in the current
invention constitutes about 0.002% to about 2% in one embodiment or
about 0.05% to about 1.5% in another embodiment or in yet another
embodiment about 0.1% to about 0.5%.
Water
[0076] Water may also be present in the oral compositions of the
invention. Water, employed in the preparation of commercial oral
compositions should be deionized and free of organic impurities.
Water commonly makes up the balance of the compositions and
includes about 10% to about 90%, about 20% to about 60% or about
10% to about 30% by weight of the oral compositions. This amount of
water includes the free water which is added plus that amount which
is introduced with other materials such as with sorbitol or any
components of the invention.
Humectants
[0077] Within certain embodiments of the oral compositions, it is
also desirable to incorporate a humectant to prevent the
composition from hardening upon exposure to air. Certain humectants
can also impart desirable sweetness or flavor to dentifrice
compositions. The humectant, on a pure humectant basis, generally
includes about 15% to about 70% in one embodiment or about 30% to
about 65% in another embodiment by weight of the dentifrice
composition.
[0078] Suitable humectants include edible polyhydric alcohols such
as glycerine, sorbitol, xylitol, propylene glycol as well as other
polyols and mixtures of these humectants. Mixtures of glycerine and
sorbitol may be used in certain embodiments as the humectant
component of the toothpaste compositions herein.
[0079] In addition to the above described components, the
embodiments of this invention can contain a variety of optional
dentifrice ingredients some of which are described below. Optional
ingredients include, for example, but are not limited to,
adhesives, sudsing agents, flavoring agents, sweetening agents,
additional antiplaque agents, abrasives, and coloring agents. These
and other optional components are further described in U.S. Pat.
No. 5,004,597, to Majeti; U.S. Pat. No. 3,959,458 to Agricola et
al. and U.S. Pat. No. 3,937,807, to Haefele, all being incorporated
herein by reference.
Methods of Manufacture
[0080] The compositions of the present invention can be made using
methods which are common in the oral product area.
[0081] In one illustrative embodiment, the oral care composition is
made by neutralizing or partially neutralizing arginine in a gel
phase with an acid, e.g., phosphoric acid, hydrochloric acid or
carbonic acid, and mixing to form Premix 1.
[0082] Actives such as, for example, vitamins, CPC, fluoride,
abrasives, and any other desired active ingredients are added to
Premix 1 and mixed to form Premix 2.
[0083] Where the final product is a toothpaste, a toothpaste base,
for example, dicalcium phosphate or silica, is added to Premix 2
and mixed. The final slurry is formed into an oral care
product.
Composition Use
[0084] The present invention in its method aspect involves applying
to the oral cavity a safe and effective amount of the compositions
described herein.
[0085] The compositions and methods according to the invention are
useful to a method to protect the teeth by facilitating repair and
remineralization, in particular to reduce or inhibit formation of
dental caries, reduce or inhibit demineralization and promote
remineralization of the teeth, reduce hypersensitivity of the
teeth, and reduce, repair or inhibit early enamel lesions, e.g., as
detected by quantitative light-induced fluorescence (QLF) or
electronic caries monitor (ECM).
[0086] Quantitative Light-induced Fluorescence is a visible light
fluorescence that can detect early lesions and longitudinally
monitor the progression or regression. Normal teeth fluoresce in
visible light; demineralized teeth do not or do so only to a lesser
degree. The area of demineralization can be quantified and its
progress monitored. Blue laser light is used to make the teeth auto
fluoresce. Areas that have lost mineral have lower fluorescence and
appear darker in comparison to a sound tooth surface. Software is
used to quantify the fluorescence from a white spot or the
area/volume associated with the lesion. Generally, subjects with
existing white spot lesions are recruited as panelists. The
measurements are performed in vivo with real teeth. The lesion
area/volume is measured at the beginning of the clinical. The
reduction (improvement) in lesion area/volume is measured at the
end of 6 months of product use. The data is often reported as a
percent improvement versus baseline.
[0087] Electrical Caries Monitoring is a technique used to measure
mineral content of the tooth based on electrical resistance.
Electrical conductance measurement exploits the fact that the
fluid-filled tubules exposed upon demineralization and erosion of
the enamel conduct electricity. As a tooth loses mineral, it
becomes less resistive to electrical current due to increased
porosity. An increase in the conductance of the patient's teeth
therefore may indicate demineralization. Generally, studies are
conducted of root surfaces with an existing lesion. The
measurements are performed in vivo with real teeth. Changes in
electrical resistance before and after 6 month treatments are made.
In addition, a classical caries score for root surfaces is made
using a tactile probe. The hardness is classified on a three point
scale: hard, leathery, or soft. In this type of study, typically
the results are reported as electrical resistance (higher number is
better) for the ECM measurements and an improvement in hardness of
the lesion based on the tactile probe score.
[0088] The Compositions of the Invention are thus useful in a
method to reduce early lesions of the enamel (as measured by QLF or
ECM) relative to a composition lacking effective amounts of
fluorine and/or arginine.
[0089] The Compositions of the invention are additionally useful in
methods to reduce harmful bacteria in the oral cavity, for example
methods to reduce or inhibit gingivitis, reduce levels of acid
producing bacteria to increase relative levels of arginolytic
bacteria, inhibit microbial biofilm formation in the oral cavity,
raise and/or maintain plaque pH at levels of at least about pH 5.5
following sugar challenge, reduce plaque accumulation, and/or clean
the teeth and oral cavity.
[0090] Finally, by increasing the pH in the mouth and discouraging
pathogenic bacteria, the Compositions of the Invention are useful
to promote healing of sores or cuts in the mouth.
[0091] Enhancing oral health also provides benefits in systemic
health, as the oral tissues can be gateways for systemic
infections. Good oral health is associated with systemic health,
including cardiovascular health. The compositions and methods of
the invention provide particular benefits because basic amino
acids, especially arginine, are sources of nitrogen which supply NO
synthesis pathways and thus enhance microcirculation in the oral
tissues. Providing a less acidic oral environment is also helpful
in reducing gastric distress and creates an environment less
favorable to Heliobacter, which is associated with gastric ulcers.
Arginine in particular is required for high expression of specific
immune cell receptors, for example T-cell receptors, so that
arginine can enhance an effective immune response. The compositions
and methods of the invention are thus useful to enhance systemic
health, including cardiovascular health.
[0092] The compositions and methods according to the invention can
be incorporated into oral compositions for the care of the mouth
and teeth such as toothpastes, transparent pastes, gels, mouth
rinses, sprays and chewing gum.
[0093] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
reference in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls. It is understood that when
formulations are described, they may be described in terms of their
ingredients, as is common in the art, notwithstanding that these
ingredients may react with one another in the actual formulation as
it is made, stored and used, and such products are intended to be
covered by the formulations described.
[0094] The following examples further describe and demonstrate
illustrative embodiments within the scope of the present invention.
The examples are given solely for illustration and are not to be
construed as limitations of this invention as many variations are
possible without departing from the spirit and scope thereof.
Various modifications of the invention in addition to those shown
and described herein should be apparent to those skilled in the art
and are intended to fall within the appended claims.
EXAMPLES
Example 1
Availability and Delivery of Antibacterial in Arginine
Formulations
[0095] Formulations are prepared using commercial toothpaste
comprising, i.a., 0.3% by weight of triclosan, 0.243% by weight of
sodium fluoride, sodium lauryl sulfate, and a copolymer of methyl
vinyl ether and maleic anhydride (PVM/MA), to which is added 0, 1%,
3%, and 5% L-arginine hydrochloride (pH 7.0).
[0096] Incorporation of L-arginine in the commercial formulation
enhances the amount of soluble triclosan available from the
formulation, from about 70% (0% arginine) to about 80% (1%
arginine), 85% (3% arginine), and 95% (5% arginine).
[0097] The formulations are tested in vitro in an artificial mouth
model designed to measure bacterial attachment to
toothpaste-treated hydroxyapatite (HAP) disks over a 24 hour
period, generally as described by Gaffar, A. et al. American
Journal of Dentistry, vol. 3, September 1990, with the modification
that the saliva-coated hydroxyapatite disks are treated with the
dentifrice slurry before exposure to bacteria. It is shown that the
incorporation of L-arginine into the commercial formulation
enhances delivery of the triclosan to the disks by about 50%, with
uptake at 30 minutes increasing from approximately 40 micrograms
triclosan per disk for the control to about 60 micrograms triclosan
for the 5% arginine formulation. After 24 hours, the control disks
have retained about 10 micrograms per disk, compared to about 20
micrograms for the 5% arginine formulation, a significant
enhancement. Similar results are achieved using histidine or lysine
in place of arginine.
[0098] This enhanced delivery leads directly to an enhancement of
the antibacterial effect of the formulation, with a statistically
significant reduction of about 15% in inhibition of growth of A.
viscosus using the 5% arginine formulation vs. control.
Example 2
Delivery of Antibacterial in Silica Based Formulations Comprising
Arginine
[0099] Toothpaste formulations comprising 5% arginine in a silica
base are prepared as follows:
TABLE-US-00001 Formula Formula Formula Formula Formula I Formula II
III IV Formula V VI VII Ingredient Wt % Wt % Wt % Wt % Wt % Wt % Wt
% L-Arginine 5.00 5.00 5.00 5.00 5.00 5.00 5.00 Hydrochloric Acid
-- -- 2.00 2.00 2.00 -- -- Silica 21.50 21.50 21.50 23.50 23.50
23.50 23.50 Sodium Fluoride 0.243 0.243 0.243 -- -- -- .0243
Glycerin 20.00 20.00 20.00 20.00 20.00 20.00 20.00 Sorbitol 20.85
20.85 20.85 20.85 20.85 20.85 20.85 Propylene Glycol 0.50 0.50 0.50
-- -- -- 2.00 Tetrasodium -- -- -- 2.00 2.00 -- 2.00 Pyrophosphate
Zinc Lactate, -- -- -- 1.4 -- -- -- Dihydrate Sodium -- -- -- --
3.00 -- -- Tripolyphosphate Sodium Lauryl 1.50 1.50 1.50 1.50 1.50
-- 1.50 Sulfate Poloxomer 407 -- -- -- -- -- 1.01 -- (Pluronic
F-127) Cocamidopropyl -- -- -- 1.01 1.01 -- 1.01 Betaine (30%
solution Hydroxy Ethyl -- -- -- 1.50 1.50 1.50 -- Cellulose Sodium
1.10 1.10 1.10 -- -- -- 1.10 carboxymethyl cellulose Carrageenan
0.4 0.4 0.4 -- -- -- 0.40 PVM/MA 2.00 2.00 2.00 -- -- -- --
copolymer Sodium -- -- -- 0.76 0.76 0.76 -- Monollurophosphate
Flavor 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Sodium Saccharin 0.30
0.30 0.30 0.50 0.50 0.50 0.50 Cationic Compatible -- -- -- -- --
15.00 -- Silica Abrasive 0.50 0.50 0.50 0.50 0.50 TiO2 Sucralose --
-- -- 0.15 0.15 0.15 -- 50% Sodium -- 1.20 -- 0.10 -- -- --
Hydroxide Solution Triclosan -- 0.30 -- -- -- -- -- Lipophilic --
-- -- -- -- 1.00 agent/Polyphenois Water (To Balance) QS QS Qs QS
QS QS QS
[0100] Triclosan uptake is studied by application of dentifrice
slurry on saliva-coated hydroxyapatite disks for a set amount of
time at 37 degrees C. The disks are rinsed to remove excess of
dentifrice on the surface. The active that is taken onto the disk
is then solubilized and analyzed by HPLC. A commercial toothpaste
having a similar formulation to formula II above, comprising, i.a.,
0.3% by weight of triclosan, 0.243% by weight of sodium fluoride,
sodium lauryl sulfate, and a copolymer of methyl vinyl ether and
maleic anhydride, but without arginine, is a positive control. This
positive control has a triclosan uptake of 32.7 micrograms per disk
vs. an uptake with Formula II of 58.8. The product with arginine
thus has an uptake that is 79.8% higher than the commercial
formulation.
[0101] In an anti-attachment test, Formula II (0.1845 reduction)
outperforms both the positive control (triclosan without arginine,
0.1809 reduction) by a slight, non-significant margin, and Formula
1 (arginine without triclosan, 0.1556 reduction) by a wider margin.
In the antibacterial test, Formula II (0.1980 reduction)
outperforms the positive control (0.1789 reduction) and Formula I
(0.1891 reduction).
Example 3
Delivery of Antibacterial in Formulations Comprising Precipitated
Calcium Carbonate
[0102] Formulations comprising 2% arginine bicarbonate are prepared
as follows:
TABLE-US-00002 RAW MATERIAL WEIGHT % Formula A Deionized Water
32.420 70% Sorbitol 23.000 Carboxymethyl cellulose 0.940 Xanthan
gum 0.210 Sodium saccharin 0.450 Sodium silicate 0.800 Sodium
bicarbonate 0.500 Arginine bicarbonate 2.000 Precipitated calcium
carbonate 36.000 Sodium monofluorophosphate 0.760 Flavor 1.000
Triclosan 0.300 Sodium lauryl sulfate 1.620 TOTAL 100.000 Formula B
Deionized Water 23.200 70% Sorbitol 23.000 Xylitol 2.500
Carboxymethyl cellulose 0.940 Xanthan gum 0.210 Sodium saccharin
0.450 Sodium silicate 0.800 Sodium bicarbonate 0.500 Arginine
bicarbonate 2.000 Precipitated calcium carbonate 42.000 Sodium
monofluorophosphate 1.100 Flavor 1.000 Triclosan 0.300 Sodium
lauryl sulfate 2.000 TOTAL 100.000 Formula C Deionized Water 34.420
70% Sorbitol 23.000 Carboxymethyl cellulose 0.940 Xanthan gum 0.210
Sodium saccharin 0.450 Sodium silicate 0.800 Sodium bicarbonate
0.500 Arginine bicarbonate 0.000 Precipitated calcium carbonate
36.000 Sodium monofluorophosphate 0.760 Flavor 1.000 Triclosan
0.300 Sodium lauryl sulfate 1.620 TOTAL 100.000
In the uptake assay described in the preceding examples, Formula A
shows 57.86 micrograms of triclosan on the disk vs. 22.88
micrograms for Formula C (control without arginine).
Example 4
Effect of Sodium Lauryl Sulfate Plus Arginine on Bacterial
Attachment
[0103] Toothpaste formulations are prepared as follows:
TABLE-US-00003 TABLE 1 Composition of Toothpaste Arg + SLS Arg w/o
SLS SLS w/o Arg Ingredients Formula 1 Formula 2 Control Glycerin 22
22 22 Sodium CMC-7MF 1 0.85 1 Tetrasodium pyrophosphate 0.25 0.25
0.25 Water 18.14 15.3 24.94 L-Arginine 5 5 0 Phosphoric Acid 1.8
1.8 0 Sodium MFP 0.76 0.76 0.76 Sodium Saccharin 0.2 0.2 0.2
Dicalcium phosphate 48.76 48.76 48.76 dihydrate Flavor 0.89 0.89
0.89 Sodium Lauryl Sulfate 1.2 0 1.2 Cocamidopropyl betaine 0 1.34
0 Polysorbate 20 0 1.68 0 Pluronic F127 0 1.17 0 Total (%) 100 100
100
Formula 1 containing both arginine and SLS shows a significant
anti-attachment effect when tested in vitro. Formula 1 is tested in
vitro in the artificial mouth model described above to measure how
much bacteria can attach to toothpaste-treated HAP disks over a 24
hour period. The results are compared to a control toothpaste which
does not contain arginine. The in vitro test shows a 27% reduction
in adhered bacteria for the HAP disks treated with Formula 1 vs.
the control sample. Formula 2 containing arginine without SLS only
shows a 10% reduction vs. the control indicating that SLS plus
arginine combination provides an unexpected advantage in inhibiting
bacterial anti-attachment. Formula 1 shows similar results to a
positive control toothpaste containing an established
anti-attachment agent.
Example 5
Effect of Sodium Lauryl Sulfate Plus Arginine Plus PVM/MA on
Bacterial Attachment
[0104] A formulation is prepared comprising arginine, sodium lauryl
sulfate and an anionic copolymer of methyl vinyl ether and maleic
anhydride (PVM/MA--Gantrez S-97):
TABLE-US-00004 Weight percent Demineralized water q.s. Sodium
saccharin 0.300 Sodium fluoride 0.243 Sorbitol 20.000 Glycerin
15.000 Sodium CMC 1.100 Carrageenan 0.400 Silica (Zeodent 115)
10.000 Silica (Zeodent 165) 3.000 Gantrez S-97 15.000 L-Arginine
5.000 Mint flavor 1.000 Sodium lauryl sulfate 1.500 Propylene
glycol 0.500
This formulation shows excellent anti-attachment properties, with
over 40% reduction in attachment vs. control.
Example 5
Mouth Rinse Formulations
[0105] Mouthwash formulations of the invention are prepared using
the following ingredients:
[0106] Arginine Rinse with Fluoride. SLS, PMV/MA, and Triclosan
TABLE-US-00005 RAW MATERIAL WEIGHT % Deionized Water q.s. Glycerin
15.000 Sodium methyl cocoyl taurate 0.250 95% Ethanol 6.000 Sodium
lauryl sulfate 0.200 Allantoin 0.110 Sodium benzoate 0.100 Sodium
salicylate 0.100 Sodium fluoride 0.050 Sodium Saccharin 0.005
Triclosan 0.030 Phosphoric acid 85% 0.120 L-Arginine 0.300 Flavor
0.100 Colorants 0.001 PVM/MA 0.250 TOTAL 100.000 pH 7.0
This formulation is effective to inhibit bacterial attachment.
Example 6
Dentifrice Formulation Comprising Precipitated Calcium Carbonate
(PCC)
[0107] A panel of consumer testers trained in testing the sensory
attributes of dentifrice formulations was subjected to different
dentifrice formulations which were used under double-blind consumer
testing conditions replicating consumer use of dentifrice
formulations.
[0108] The panel was asked to use the dentifrice formulations
conventionally and then to rate various sensory characteristics.
For a base dentifrice formulation comprising precipitated calcium
carbonate (PCC), the known formulation acted as a placebo control,
and corresponding formulations additionally comprising 1, 2, 3 or 5
wt % arginine bicarbonate were also tested. Surprisingly, it was
found that the arginine bicarbonate-containing PCC formulations
exhibited increases in consumer acceptance for flavor intensity,
cooling and ease to foam attributes, and moreover the formulation
additionally comprising 2 wt % arginine bicarbonate exhibited
increases in overall liking, overall liking of taste, taste while
brushing and taste after brushing. In addition, the formulations
additionally comprising arginine bicarbonate were perceived as
significantly better than the placebo control in all image
attributes, including perceived efficacy, mouth/teeth feeling of
clean, product suitability, taste and overall product quality.
[0109] In contrast, when formulations having dicalcium phosphate,
rather than precipitated calcium carbonate (PCC), as the base were
tested, the addition of arginine bicarbonate did not exhibit
significantly improved sensory characteristics as compared to the
same formulation without the addition of arginine bicarbonate.
[0110] The Example shows that the addition of a basic amino acid
such as arginine, in particular as bicarbonate, can surprisingly
enhance the sensory characteristics of dentifrice formulations,
most particularly having a base formulation of precipitated calcium
carbonate (PCC), when used in an oral care composition of the
invention.
Example 7
Basic Amino Acids Other than Arginine
[0111] An overnight culture of S. sanguis was grown at 37.degree.
C. in trypticase soy broth (Becton Dickinson, Sparks, Md.). The
culture was centrifuged at 5,000 rpm for 5 minutes at 1 milliliter
at a time into preweighed tubes in order to accumulate
approximately 5 milligrams of wet pellet weight. The pellet was
then resuspended into 20 millimolar potassium phosphate buffer (JT
Baker, Phillipsburg, N.J.), pH 4.0, to simulate a stressed
environment for the bacterial cell where ammonia would be produced
for survival. The final concentration was 5 milligram per
milliliter. To this final concentration, a 5 millimolar final
concentration of L-arginine, L-citrulline, or L-ornithine was added
along with a 0.1% final concentration of sucrose (VWR, West
Chester, Pa.). This mixture was then incubated at 37.degree. C. in
a shaking water bath for 30 minutes before ammonia production was
determined.
[0112] In order to analyze for ammonia, an Ammonia Assay kit was
used from Diagnostic Chemicals Limited (Oxford, Conn.). The
intended use of this specific kit is for the in vitro
quantification of ammonia in plasma, but the procedure was modified
in order to determine and quantify the ammonia production in plaque
and/or bacteria.
[0113] The table below shows the ammonia production values from 6
separate trials using S. sanguis at pH 4.0 as described above. The
results confirm that the intermediates produced by the arginine
deiminase system can be used to produce ammonia for cell
survival.
TABLE-US-00006 L-Arginine L-Citrulline L-Ornithine Trial # Ammonia
(ppm) Ammonia (ppm) Ammonia (ppm) 1 0.509 0.185 0.185 2 0.866 0.346
0.260 3 2.20 0.332 0.047 4 1.62 0.194 0.0 5 0.5 0.226 0.181 6 0.679
0.951 0.135 Mean 1.06 0.951 0.134
[0114] The Example shows that basic amino acids other than arginine
are effective to produce ammonia within the oral cavity, and thus
to increase plaque pH when used in a oral care composition of the
invention.
[0115] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
reference in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls. It is understood that when
formulations are described, they may be described in terms of their
ingredients, as is common in the art, notwithstanding that these
ingredients may react with one another in the actual formulation as
it is made, stored and used, and such products are intended to be
covered by the formulations described.
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