U.S. patent application number 15/270450 was filed with the patent office on 2017-01-12 for oral care compositions.
The applicant listed for this patent is COLGATE-PALMOLIVE COMPANY. Invention is credited to Marilou Joziak, Andre Morgan, Michael Prencipe.
Application Number | 20170007529 15/270450 |
Document ID | / |
Family ID | 45476656 |
Filed Date | 2017-01-12 |
United States Patent
Application |
20170007529 |
Kind Code |
A1 |
Morgan; Andre ; et
al. |
January 12, 2017 |
ORAL CARE COMPOSITIONS
Abstract
Disclosed herein are compositions comprising a fluoride ion
source, a poly(propylene oxide)/poly(ethylene oxide) copolymer, and
optionally a sparingly soluble acid; and methods of using and of
making the same.
Inventors: |
Morgan; Andre;
(Robbinsville, NJ) ; Joziak; Marilou; (South
River, NJ) ; Prencipe; Michael; (Princeton Junction,
NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
COLGATE-PALMOLIVE COMPANY |
New York |
NY |
US |
|
|
Family ID: |
45476656 |
Appl. No.: |
15/270450 |
Filed: |
September 20, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14365690 |
Jun 16, 2014 |
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PCT/US2011/066074 |
Dec 20, 2011 |
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15270450 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/368 20130101;
A61K 8/19 20130101; A61K 2800/54 20130101; A61K 8/362 20130101;
A61K 8/21 20130101; A61K 8/24 20130101; A61K 8/25 20130101; A61K
8/86 20130101; A61K 8/81 20130101; A61K 8/49 20130101; A61P 1/02
20180101; A61K 8/463 20130101; A61Q 11/00 20130101 |
International
Class: |
A61K 8/86 20060101
A61K008/86; A61K 8/362 20060101 A61K008/362; A61Q 11/00 20060101
A61Q011/00; A61K 8/21 20060101 A61K008/21; A61K 8/19 20060101
A61K008/19 |
Claims
1. An oral care composition comprising: a fluoride ion source; and
a poly(propylene oxide)/poly(ethylene oxide) copolymer in an amount
effective to provide greater than 90% recovery of soluble fluoride
ions after 3 months at 40.degree. C., wherein the poly(propylene
oxide)/poly(ethylene oxide) copolymer is present in an amount of
from about 2.5% to about 5%, by weight, of the composition.
2. The composition of claim 1, further comprising a sparingly
soluble acid in an amount effective to enhance delivery of fluoride
to the enamel.
3. The composition of claim 1, wherein the poly(propylene
oxide)/poly(ethylene oxide) copolymer has a molecular weight of
from about 8,000 to about 18,000 g/mol, and an ethylene oxide
content of from about 30 to about 90%, by weight of the
copolymer.
4. The composition of claim 1, wherein the poly(propylene
oxide)/poly(ethylene oxide) copolymer has a molecular weight of
from about 12,000 to about 15,000 g/mol, and an ethylene oxide
content of from about 70 to about 80%, by weight of the
copolymer.
5. The composition of claim 1, wherein the poly(propylene
oxide)/poly(ethylene oxide) copolymer is selected from: Poloxamer
237; Poloxamer 217; Poloxamer 184; Poloxamer 185; Poloxamer 188;
Poloxamer 338; Poloxamer 407; and a combination of two or more
thereof.
6. The composition of claim 3, wherein the poly(propylene
oxide)/poly(ethylene oxide) copolymer is selected from Poloxamer
237; Poloxamer 188; Poloxamer 338; Poloxamer 407; and a combination
of two or more thereof.
7. The composition of claim 1, wherein the poly(propylene
oxide)/poly(ethylene oxide) copolymer is selected from: Poloxamer
338; Poloxamer 407; and a combination of two or more thereof.
8. (canceled)
9. (canceled)
10. The composition of claim 1, wherein the sparingly soluble acid
is present in an amount of from about 0.01 to about 0.25%, of the
total composition weight.
11. The composition of claim 1, wherein the fluoride ion source is
selected from stannous fluoride, sodium fluoride, potassium
fluoride, sodium monofluorophosphate, sodium fluorosilicate,
ammonium fluorosilicate, amine fluoride, ammonium fluoride,
titanium fluoride, hexafluorosulfate, silver diamine fluoride,
indium 10 fluoride, zinc fluoride, and a combination of two or more
thereof.
12. The composition of claim 1, wherein the fluoride ion source is
present in an amount of about 0.01 wt. % to about 2 wt. % of the
total composition weight.
13. The composition of claim 1, wherein the pH is about 6.5 to
about 7.5 in undiluted form, and wherein the pH of the composition
is lowered from about 0.6 to about 2 pH units, during use.
14. The composition of claim 1 any foregoing claim 1, further
comprising a calcium ion source.
15. The composition of claim 14, wherein the calcium ion source is
tricalcium phosphate hydroxyapatite, dicalcium phosphate dihydrate,
calcium pyrophosphate, amorphous calcium phosphate, or mixtures
thereof present in an amount of about 0.01 to about 1% of the total
composition weight.
16. The composition of claim 1, in a form selected from: a
mouthrinse, a toothpaste, a tooth gel, a tooth powder, a
non-abrasive gel, an oral care mousse, a foam, mouth spray, a
lozenge, a tablet, a dental implement, and a pet care product.
17. A method of enhancing delivery of fluoride to tooth enamel
comprising applying an effective amount of the composition
according to any foregoing claim to the oral cavity of a subject in
need thereof.
18. A method of enhancing protection of teeth against caries and
cavities and increasing resistance to acid demineralization
comprising administering to the oral cavity, of a subject in need
thereof, a composition according to claim 1.
19. Use of a composition according to claim 1, for the manufacture
of a medicament for enhancing protection of teeth against caries
and cavities and increasing resistance to acid
demineralization.
20. Use of a composition according to claim 1, for enhancing
protection of teeth against caries and cavities and increasing
resistance to acid demineralization.
21. A composition according to claim 1 for use in enhancing
delivery of fluoride to tooth enamel.
22. A composition according to claim 1 for use in enhancing
protection of teeth against caries and cavities and increasing
resistance to acid demineralization.
Description
BACKGROUND
[0001] Fluoride is one of the best known agents used to combat
dental caries. In order for fluoride to be effective it must be
soluble in the formula and efficiently delivered to the enamel
surface upon dilution. The choice of formulation ingredients plays
a key role in determining whether or not fluoride is effectively
delivered to the enamel surface upon use. It is therefore critical
to choose the appropriate type and level of formula excipients to
ensure that one gets the full benefit of the fluoride incorporated
in a product.
SUMMARY
[0002] The present inventors have discovered that incorporating
nonionic block copolymers (i.e., poloxomers) alone or in
combination with sparingly soluble acids into a fluoride containing
formulation enhances the bioavailability of fluoride therefrom and
subsequently enhances fluoride uptake and remineralization of
enamel surfaces using these formulations.
[0003] Some embodiments of the present invention provide an oral
care composition comprising: a fluoride ion source, an effective
amount of a poly(propylene oxide)/poly(ethylene oxide) copolymer;
and optionally, an effective amount of a sparingly soluble acid for
enhancing fluoride delivery.
[0004] Other embodiments provide methods of enhancing delivery of
fluoride to tooth enamel comprising applying an effective amount of
any of the compositions described herein to the oral cavity of a
subject in need thereof.
[0005] Still further embodiments provide methods of enhancing
protection of teeth against caries and cavities and increasing
resistance to acid demineralization comprising administering to the
oral cavity, of a subject in need thereof, a composition as
described herein.
[0006] Yet other embodiments provide the use of a composition as
described herein for the manufacture of a medicament for enhancing
protection of teeth against caries and cavities and increasing
resistance to acid demineralization.
[0007] In some embodiments, the compositions demonstrate a Vickers
Hardness Number ("VHN"), which correlates with an acceptable level
of enamel remineralization.
DETAILED DESCRIPTION
[0008] The pH of a dentifrice, such as a toothpaste or gel, should
be at or near neutral in order for the formulation to maintain
stability prior to use. However, fluoride delivery to the tooth
enamel is enhanced at a more acidic pH. It has been surprisingly
discovered that the addition of an appropriate amount of block
copolymer to a fluoride containing composition will provide a
stable composition on storage (maintaining a near neutral pH), but
will lower the pH of the composition upon use to an extent
sufficient to enhance delivery of fluoride ions to the tooth
enamel. Such enhanced delivery of fluoride ions to teeth results in
remineralization of tooth enamel surfaces.
[0009] As used herein, the term "enhanced delivery" or "enhancing
the delivery" refers to the increased availability or uptake of an
ingredient at the target site, e.g. increased uptake of fluoride in
tooth enamel.
[0010] The present inventors have surprisingly discovered that the
presence of certain amounts of a block copolymer and a sparingly
soluble acid in a fluoride containing composition, provides a
composition which: (1) is stable during packaging and storage; (2)
demonstrates a reduced pH upon dilution in an aqueous liquid (e.g.
during brushing); thereby providing enhanced delivery of fluoride
to the tooth enamel.
[0011] In some embodiments, compositions of the present invention
have a pH, prior to use, of from about 5 to about 9. In some
embodiments, compositions of the present invention have a pH, prior
to use, of from about 6 to about 8. In other embodiments,
compositions of the present invention have a pH, prior to use, of
from about 6.7 to about 7.3. In further embodiments, compositions
of the present invention have a pH, prior to use, of from about 6.8
to about 7.2. In some embodiments, compositions of the present
invention have a pH, prior to use, of about 7.
[0012] In some embodiments, the present invention provides
compositions which are single-phase compositions.
[0013] During typical use a composition of the invention such as a
dentifrice is diluted in an aqueous liquid, e.g., water or saliva,
to about 3:1, wherein the ratios are liquid:composition. In some
embodiments, the pH of the compositions decrease by from about 0.6
to about 1.5 pH units, during use. In some embodiments, the pH of
the compositions decrease by from about 0.7 to about 1.4 pH units.
In some embodiments, the pH of the compositions decrease by from
about 0.8 to about 1.3 pH units, during use. In some embodiments,
the pH of the compositions decrease by from about 0.9 to about 1.2
pH units, during use. In some embodiments, the pH of the
compositions decrease by about 1 pH unit, during use.
[0014] In some embodiments, the time period of use is from about 15
seconds to about 180 seconds. In some embodiments, the time period
of use is from about 30 seconds to about 120 seconds. In some
embodiments, the time period of use is about 45 seconds. In some
embodiments, the time period of use is about 60 seconds. In some
embodiments, the time period of use is about 90 seconds. In some
embodiments, the time period of use is about 120 seconds.
[0015] In some embodiments, enamel fluoride uptake (EFU) is
evaluated using FDA Monograph #40. In some embodiments, EFU can be
evaluated using any suitable means known to those skilled in the
art.
[0016] In some embodiments, the compositions of the present
invention comprise a fluoride ion source and a poly(propylene
oxide)/poly(ethylene oxide) copolymer, wherein the copolymer is
present in an amount effective to provide a stable formulation on
storage and deliver an effective amount of fluoride during use. In
some embodiments, the copolymer is present in an amount effective
to maintain the pH of the composition in the range of from about
6.5 to about 7.5. In some embodiments, the copolymer is present in
an amount effective to reduce the pH by about 1 pH unit during
use.
[0017] In some embodiments, the copolymer is present in an amount
effective to provide an enamel fluoride uptake (e.g. EFU) of at
least about 40% of the theoretical fluoride concentration contained
in the initial formulation. In some embodiments, the copolymer is
present in an amount effective to provide an EFU of at least 30%
greater than a suitable control.
[0018] In some embodiments, the copolymer is selected from:
Poloxamer 338, Poloxamer 407, Poloxamer, 237, Poloxamer, 217,
Poloxamer 124, Poloxamer 184, Poloxamer 185, and a combination of
two or more thereof. In some embodiments, the copolymer is
Poloxamer 338. In some embodiments, the copolymer is Poloxamer 407.
In some embodiments, the copolymer is Poloxamer 188. In some
embodiments, the copolymer is Poloxamer 124.
[0019] In some embodiments, the copolymer is present in the amount
of about 0.1 to about 10% of the total composition weight. In some
embodiments, the copolymer is present in the amount of about 2.5%
to about 5% of the total composition weight. In some embodiments,
the copolymer is present in the amount of about 2.5% of the total
composition weight. In some embodiments, the copolymer is present
in the amount of 5% of the total composition weight.
[0020] Some embodiments of the present invention further comprise
an effective amount of a sparingly soluble acid. As used herein,
the term "sparingly soluble acid" means an acid having a water
solubility of about 0.1 g/100 ml to about 30 g/100 ml in water at
25.degree. C. In some embodiments, the sparingly soluble acid has a
water solubility of about 0.5 g/100 ml to about 15 g/100 ml in
water at 25.degree. C.
[0021] In some embodiments, the sparingly soluble acid is an
organic sparingly soluble acid. In other embodiments, the sparingly
soluble acid is an acid phosphate salt. In some embodiments, the
sparingly soluble acid is sodium acid pyrophosphate, sodium
aluminum phosphate, monopotassium phosphate, or a mixture thereof.
In some embodiments, the sparingly soluble acid is selected from:
fumaric acid, propionic acid, pentanoic acid, and a combination of
two or more thereof. In some embodiments, the sparingly soluble
acid is fumaric acid.
[0022] In some embodiments, the sparingly soluble acid is present
in an amount of about 0.01 to less than about 0.5%, of the total
composition weight. In some embodiments, the sparingly soluble acid
is present in an amount of about 0.0125 to less than about 0.5% of
the total composition weight. In some embodiments, the sparingly
soluble acid is present in an amount of about 0.05 to less than
about 0.5% of the total composition weight. In some embodiments,
the sparingly soluble acid is present in an amount of about 0.1 to
less than about 0.5% of the total composition weight. In some
embodiments, the sparingly soluble acid is present in an amount of
about 0.25 to less than about 0.5% of the total composition weight.
In some embodiments, the sparingly soluble acid is present in an
amount of about 0.05% of the total composition weight.
[0023] In some embodiments, the fluoride ion source is selected
from 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 a
combination of two or more thereof.
[0024] In some embodiments, the fluoride ion source is selected
from sodium fluoride and sodium monofluorophosphate. In some
embodiments, the fluoride ion source comprises sodium fluoride. In
some embodiments, the fluoride ion source is present in an amount
of about 0.01% to about 2% of the total composition weight. In some
embodiments, the fluoride ion source is present in an amount of
about 0.1% to about 0.2% of the total composition weight.
[0025] In some embodiments, the fluoride ion source is present in
an amount effective to provide greater than about 1000 ppm fluoride
ion. In some embodiments, the fluoride ion source is present in an
amount effective to provide greater than about 2000 ppm fluoride
ion. In some embodiments, the fluoride ion source is present in an
amount effective to provide greater than 2250 ppm fluoride ion. In
some embodiments, the fluoride ion source is present in an amount
effective to provide greater than about 2500 ppm fluoride ion. In
some embodiments, the fluoride ion source is present in an amount
effective to provide greater than about 2750 ppm fluoride ion.
[0026] In some embodiments, the compositions further comprise a
calcium ion source. In some embodiments, the calcium ion source is
selected from: tricalcium phosphate, hydroxyapatite, dicalcium
phosphate dehydrate, calcium pyrophosphate, amorphous calcium
phosphate, and a combination of two or more thereof. In some
embodiments, the calcium ion source comprises tricalcium
phosphate.
[0027] In some embodiments, the compositions comprise from about
0.01% to about 10% by weight of a calcium ion source. In other
embodiments, the composition comprises from about 0.01% to about 1%
by weight of a calcium ion source. In further embodiments, the
composition comprises from about 0.02% to about 0.2% by weight of a
calcium ion source. In some embodiments, the composition comprises
about 0.0775%, by weight, of a calcium ion source.
[0028] Some embodiments of the present invention comprise an
abrasive. In some embodiments, the abrasive is selected from:
sodium bicarbonate, calcium phosphate (e.g., dicalcium phosphate
dihydrate), calcium sulfate, precipitated calcium carbonate, silica
(e.g., hydrated silica), iron oxide, aluminum oxide, coated
alumina, perlite, and a combination of two or more thereof. In some
embodiments, the compositions comprise from about 15% to about 70%
of the total composition weight.
[0029] In some embodiments, the compositions comprise an abrasive
having a small particle (d50 of <5 micrometers) fraction of at
least about 5%.
[0030] Some embodiments provide a composition comprising an anionic
surfactant 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 cocomono-glyceride
sulfate); b. higher alkyl sulfates, e.g., sodium lauryl sulfate; c.
higher alkyl-ether sulfates, e.g., of formula
[0031]
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
sulfoacetamide) and sodium lauryl sarcosinate); f. and mixtures
thereof.
[0032] By "higher alkyl" is meant, e.g., C.sub.6-30 alkyl. In some
embodiments, the anionic surfactant is selected from sodium lauryl
sulfate and sodium ether lauryl sulfate.
[0033] In some embodiments, the anionic surfactant is present in an
amount of from about 0.3% to about 4.5% by weight of the
composition.
[0034] Some embodiments further comprise a surfactant selected from
a cationic surfactant, a zwitterionic surfactant, a nonionic
surfactant, and a combination of two or more thereof.
[0035] In some embodiments, the compositions further comprise a
humectant. In some embodiments, the humectant is selected from
glycerin, sorbitol, xylitol and a combination of two or more
thereof. In some embodiments, the composition comprises
xylitol.
[0036] In some embodiments, the compositions further comprise a
polymer in addition to the poly(propylene oxide)/poly(ethylene
oxide) block copolymer. In some embodiments, the additional polymer
is selected from a polyethylene glycol, a polyvinylmethyl ether
maleic acid copolymer, a polysaccharides (e.g., a cellulose
derivative, for example carboxymethyl cellulose, or a
polysaccharide gum, e.g., xanthan gum or carrageenan gum), and a
combination of two or more thereof.
[0037] Some embodiments further comprise an antibacterial agent
selected from a halogenated diphenyl ether (e.g. triclosan), a
magnolol derivative, an herbal extract or essential oil (e.g.,
rosemary extract, tea extract, thymol, menthol, eucalyptol,
geraniol, carvacrol, citral, hinokitol, catechol, methyl
salicylate, epigallocatechin gallate, epigallocatechin, gallic
acid, miswak extract, sea-buckthorn extract), a bisguanide
antiseptic (e.g., chlorhexidine, alexidine or octenidine), a
quaternary ammonium compound (e.g., cetylpyridinium chloride (CPC),
benzalkonium chloride, tetradecylpyridinium chloride (TPC),
N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), a phenolic
antiseptic, hexetidine, octenidine, sanguinarine, povidone iodine,
delmopinol, salifluor, metal ions (e.g., zinc salts, for example,
zinc citrate, a stannous salt, a copper salt, an iron salt),
sanguinarine, propolis and an oxygenating agent (e.g., hydrogen
peroxide, buffered sodium peroxyborate or peroxycarbonate),
phthalic acid or a salt thereof, monoperthalic acid or a salt or
ester thereof, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate,
dioctyl sulfosuccinate, salicylanilide, domiphen bromide,
delmopinol, octapinol or another piperidino derivative, a nicin
preparation, a chlorite salt; and a combination of two or more
thereof.
[0038] In some embodiments, the antibacterial agent is present in
an amount of about 0.01% to about 5% of the total composition
weight. In other embodiments, the antibacterial is triclosan. In
some embodiments, the triclosan is present in an amount of 0.01 to
1% of the total composition weight. Some embodiments provide
compositions wherein the triclosan is present in the amount of
about 0.3% of the total composition weight.
[0039] Some embodiments of the present invention provide methods
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 or inhibit gingivitis, (v) clean the teeth and oral cavity
(vi) reduce erosion, (vii) whiten teeth; and/or (viii) promote
whole body health.
[0040] In some embodiments, the composition is in the form of a
toothpaste.
[0041] Some embodiments further comprise an anti-calculus agent. In
some embodiments, the anti-calculus agent is a polyphosphate, e.g.,
pyrophosphate, tripolyphosphate, or hexametaphosphate, e.g., in
sodium salt form.
[0042] In some embodiments, the compositions 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.
[0043] The silica abrasives useful herein, as well as the other
abrasives, generally have an average particle size ranging between
about 0.1 and about 30 microns, about between 5 and 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.
[0044] In some embodiments, the abrasive materials comprise a large
fraction of very small particles, e.g., having a d50<5 microns,
for example, small particle silica (SPS) having a d50 of about 3 to
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% SPS and about 25 to about 45% of a conventional
abrasive.
[0045] 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 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.
[0046] 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. Illustrative examples of agents that
increase the amount of foam include, but are not limited to
polyoxyethylene and certain polymers including, but not limited to,
alginate polymers. The polyoxyethylene may increase the amount of
foam and the thickness of the foam generated by the oral care
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.
[0047] 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.
[0048] 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. The flavoring agent can be 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 about 0.015% by weight.
[0049] In some embodiments, when noncationic antibacterial agents
or antibacterial agents, e.g., triclosan, are included in any of
the dentifrice components, there may also be included from about
0.05 to about 5% of an agent which enhances the delivery 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 1:4 to 4:1 copolymers of maleic
anhydride or acid with another polymerizable ethylenically
unsaturated monomer, preferably methyl vinyl etherimaleic 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.
[0050] 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.
[0051] 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.
[0052] In some embodiments, the compositions of the present
invention can be manufactured as follows. Poloxamer is first
dissolved in formula amount of water. Next, fluoride salts,
sweeteners, and any other water soluble excipients are added to the
poloxamer containing mixture, and mixed until dissolved. In a
separate vessel, polymer gums/binding agents are added to the
humectants, and mixed until dispersed. The polymer/humectant
mixture is then added to the poloxamer/salt mixture described
above, and mixed to create the gel phase. The abrasives are then
added to the gel phase in a suitable vessel and mixed under vacuum
to create a smooth dentifrice. Finally, surfactants, flavoring
agent, and sparingly soluble acid are added to the dentifrice, and
mixed under vacuum until homogeneous.
[0053] 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.
[0054] 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
[0055] Table 1 (below) describes the formulations of a composition
according to some embodiments of the present invention (Formulae
I-VI) and comparative examples (CI-CIV).
TABLE-US-00001 TABLE 1 Ingredient I II III IV V VI CI CII CIII CIV
Sorbitol 39.5 39.5 39.5 39.5 39.5 39.5 39.5 39.5 39.5 39.5 Water QS
QS QS QS QS QS QS QS QS QS Abrasive silica 8 8 8 8 8 8 8 8 8 8
Silica 3 3 3 3 3 3 3 3 3 3 thickener Polyethylene 3 3 3 3 3 3 3 3 3
3 glycol 600 Sodium lauryl 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2
sulfate Sodium 1.105 1.105 1.105 1.105 1.105 1.105 1.105 1.105
1.105 1.105 fluoride Flavor 1 1 1 1 1 1 1 1 1 1 Xanthan gum 0.8 0.8
0.8 0.8 0.8 0.8 0.8 0.8 0.8 0.8 Sodium 0.5 0.5 0.5 0.5 0.5 0.5 0.5
0.5 0.5 0.5 benzoate Sodium 0.35 0.35 0.35 0.35 0.35 0.35 0.35 0.35
0.35 0.35 saccharin PEO-PPO 5 5 5 5 5 5 -- 1.5 5 5 Block Copolymer
Fumaric acid -- 0.05 0.0125 0.35 -- 0.05 -- 0.05 0.5 -- Sodium acid
-- -- 0.25 -- -- -- 0.5 pyrophosphate Tricalcium 0.0775 Phosphate
Sodium 1.05 Phosphate Monobasic Tetrapotassium 0.63 Pyrophosphate
Sodium 0.5 Hydroxide- 50% FCC
Example 2
[0056] Enamel fluoride uptake (EFU) is evaluated according to FDA
Monograph Method #40, except the carries lesion was formed using a
solution that is 0.1M lactic acid and 0.2% Carbopol 907 and is 50%
saturated with hydroxyapatite (HAP) at a pH of 5.0. The method
involved first forming an artificial caries lesion on the enamel
specimens using the lesion forming solution described above. The
specimens were then rinsed with deionized water, and subsequently
treated with a slurry (1 part paste: 3 parts water) of the
respective dentifrice. Next, the treated specimens were etched with
a HClO.sub.4 solution for 15 seconds to remove the delivered
fluoride ion; the etching solution was then buffered with Total
Ionic Strength Adjustment Buffer (TISAB) to pH 5.2, and analyzed
for fluoride ions by ion selective electrode (ISE). Fluoride
content was determined for each solution based on a calibration
curve.
TABLE-US-00002 TABLE 2 Avg Composition EFU STDEV CI 1430 57 I 2293
59 II 2883 76
[0057] The data described in Table 2 (above) demonstrates that
compositions of the present invention deliver fluoride to the
enamel to a significantly greater extent than compositions which do
not contain the inventive combinations described herein.
Example 3
[0058] In addition to enamel fluoride uptake, the compositions are
also analyzed for their ability to promote enamel lesion
remineralization using the Vickers Hardness methodology, which
simulates in vivo caries formation. This experiment involves a
cyclic treatment regimen, consisting of 4 hr/day acid challenge of
the enamel specimens using a demineralization solution, and four
one minute dentifrice treatment. After the treatments, the
specimens are rinsed with DI water and stored in remineralizing
solution. The regimen is repeated for 20 days. After 20 days, the
degree of remineralization is determined by measuring the change in
surface micro hardness of the specimens following treatment and the
initial micro hardness.
[0059] Table 3 (below) illustrates the change in surface micro
hardness after 20 days treatment. The data described in Table 3
demonstrates that an exemplary composition of the present invention
(Formula II) promotes enamel lesion remineralization to a
significantly greater extent after 20 days, than a fluoride
containing composition which does not contain the inventive
combinations described herein.
TABLE-US-00003 TABLE 3 Hardness Composition (VHN) STD CI 10.7 1.1
II 61.1 3.9
Example 4
[0060] Exemplary compositions of the present invention, which
contain a calcium ion source, are also analyzed for their ability
to promote enamel lesion remineralization using the Vickers
Hardness methodology. The experiment is conducted as described in
Example 3 (above). The regimen is repeated for 10 days. After 10
days, the degree of remineralization is determined by measuring the
change in surface micro hardness of the specimens following
treatment and the initial micro hardness.
[0061] The data described in Table 4 (below) further illustrates
that exemplary compositions of the present invention (e.g. Formulae
II and VI) promote enamel lesion remineralization to a
significantly greater extent after 10 days, than a fluoride
containing composition which does not contain the inventive
combinations described herein.
TABLE-US-00004 TABLE 4 Hardness Composition (VHN) STD CI 12.9 1.0
II 53.1 4.0 VI 70.9 6.8
Example 5
[0062] Exemplary compositions of the present invention are
evaluated for their ability to provide fluoride stability to the
formulation. The results are reported in Table 5 (below).
TABLE-US-00005 TABLE 5 Soluble Fluoride Soluble Fluoride
Composition Initial pH Initial 3 Mon 40.degree. C. CIV 6.93 3720
n/a Formula II 7.18 5206 5200 Formula V 7.13 4808 4703
[0063] The data described in Table 5 (above) demonstrates that
compositions of the present invention (e.g. Formula II and Formula
V), provide >90% soluble fluoride recovery upon accelerated
aging, while a comparative composition (CIV) that does not include
the inventive combinations discovered by the present inventors, is
unable to maintain an adequate level of fluoride stability.
* * * * *