U.S. patent application number 15/548272 was filed with the patent office on 2018-01-25 for oral care compositions and methods of use.
This patent application is currently assigned to Colgate-Palmolive Company. The applicant listed for this patent is Colgate-Palmolive Company. Invention is credited to Andre MORGAN, Michael PRENCIPE, Amy RUSSO, Hansruedi STETTLER.
Application Number | 20180021234 15/548272 |
Document ID | / |
Family ID | 56297163 |
Filed Date | 2018-01-25 |
United States Patent
Application |
20180021234 |
Kind Code |
A1 |
PRENCIPE; Michael ; et
al. |
January 25, 2018 |
Oral Care Compositions and Methods of Use
Abstract
This invention relates to oral care compositions comprising
arginine or lysine, zinc citrate and zinc oxide, and a fluoride
source, as well as to methods of using and of making these
compositions.
Inventors: |
PRENCIPE; Michael; (West
Windsor, NJ) ; RUSSO; Amy; (Belle Mead, NJ) ;
STETTLER; Hansruedi; (Basel, CH) ; MORGAN; Andre;
(Robbinsville, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Colgate-Palmolive Company |
New York |
NY |
US |
|
|
Assignee: |
Colgate-Palmolive Company
New York
NY
|
Family ID: |
56297163 |
Appl. No.: |
15/548272 |
Filed: |
June 24, 2016 |
PCT Filed: |
June 24, 2016 |
PCT NO: |
PCT/US2016/039194 |
371 Date: |
August 2, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62187801 |
Jul 1, 2015 |
|
|
|
Current U.S.
Class: |
424/52 |
Current CPC
Class: |
A61K 8/345 20130101;
A61K 2800/28 20130101; A61K 8/27 20130101; A61K 8/21 20130101; A61P
1/02 20180101; A61K 8/25 20130101; A61K 8/362 20130101; A61P 31/02
20180101; A61Q 11/00 20130101; A61K 8/44 20130101; A61P 31/04
20180101; A61K 2800/92 20130101; A61K 8/365 20130101 |
International
Class: |
A61K 8/44 20060101
A61K008/44; A61K 8/27 20060101 A61K008/27; A61Q 11/00 20060101
A61Q011/00; A61K 8/21 20060101 A61K008/21 |
Claims
1. An oral care composition comprising: a. A basic amino acid in
free or salt form wherein the amino acid is selected from arginine,
lysine, and combinations thereof. b. zinc oxide and zinc citrate c.
a fluoride source.
2. The oral care composition of claim 1, wherein the basic amino
acid is arginine or lysine and wherein the arginine or lysine has
the L-configuration.
3. The oral care composition of claim 1, wherein the amino acid is
arginine or lysine wherein the arginine or lysine is present in an
amount corresponding to 0.1% to 15%, based on the total weight of
the composition, the weight of the basic amino acid being
calculated as free form.
4. The oral care composition of claim 1 wherein the amino acid is
arginine or lysine wherein the arginine or lysine is present in an
amount corresponding to 0.1% to 8%, based on the total weight of
the composition, the weight of the basic amino acid being
calculated as free form.
5. The oral care composition of claim 1 wherein the amino acid is
arginine from about 1.5 wt. %, based on the total weight of the
composition, the weight of the basic amino acid being calculated as
free form.
6. The oral care composition of claim 1 wherein the amino acid is
arginine from about 5.0 wt. %, based on the total weight of the
composition, the weight of the basic amino acid being calculated as
free form.
7. The oral care composition of claim 1 wherein the amino acid is
arginine from about 8.0 wt. %, based on the total weight of the
composition, the weight of the basic amino acid being calculated as
free form.
8. The oral care composition of claim 1 wherein the amino acid is
arginine in free form.
9. The oral care composition of claim 1 wherein the amino acid is
lysine and wherein the lysine is L-lysine.
10. The oral care composition of claim 9, wherein the lysine is
about 4.0 wt. %, based on the total weight of the composition, the
weight of the lysine being calculated as free form.
11. The oral care composition of claim 1 wherein the amino acid is
lysine in free form.
12. The oral care composition of claim 1 wherein the amino acid is
arginine or lysine in partially or wholly salt form.
13. The oral care composition of claim 1, wherein the ratio of the
amount of zinc oxide (by wt %) to zinc citrate (by wt %) is 2:1,
2.5:1, 3:1, 3.5:1 or 4:1, wherein the ratio is by wt. of the
overall composition.
14. The oral care composition of claim 13, wherein the ratio of the
amount of zinc oxide (by wt %) to zinc citrate (by wt %) is
2:1.
15. The oral care composition of claim 1, wherein the zinc citrate
is in an amount of from 0.25 to 1.0 wt % and zinc oxide may be
present in an amount of from 0.75 to 1.25 wt % based on the total
weight of the composition.
16. The oral care composition of claim 1, wherein the zinc citrate
is in an amount of about 0.5 wt % and zinc oxide is present in an
amount of about 1.0% based on the total weight of the
composition.
17. The oral care composition of claim 1, wherein the fluoride
source is sodium fluoride or sodium monofluorophosphate.
18. The oral care composition of claim 17, wherein the sodium
fluoride or sodium monofluorophosphate is from 0.1 wt.%-2 wt. %
based on the total weight of the composition.
19. The oral care composition of claim 17 wherein the sodium
fluoride or sodium monofluorophosphate is a soluble fluoride salt
which provides soluble fluoride in amount of 50 to 25,000 ppm
fluoride.
20. The composition of claim 19, wherein sodium fluoride provides
soluble fluoride in an amount of about 1450 ppm.
21. The composition of claim 19, wherein sodium fluoride provides
soluble fluoride in an amount of about 1000 ppm-1500 ppm.
22. The composition of claim 1, wherein the fluoride source is
sodium fluoride in an amount about 0.32% by wt, based on the total
weight of the composition.
23. The composition of claim 1, wherein the fluoride source is
stannous fluoride.
24. The oral care composition of claim 1 further comprising a
preservative selected from: benzyl alcohol, Methylisothizolinone
("MIT"), Sodium bicarbonate, sodium methyl cocoyl taurate
(tauranol), lauryl alcohol, and polyphosphate.
25. The oral care composition of claim 1 comprising benzyl alcohol
in an amount of from 0.1-0.8% wt %, based on the total weight of
the composition.
26. The oral care composition of claim 1 comprising benzyl alcohol
in an amount of from 0.3-0.5% wt %, based on the total weight of
the composition.
27. The oral care composition of claim 25, wherein the benzyl
alcohol is about 0.4 wt % based on the total weight of the
composition.
28. The oral care composition of claim 1 comprising: a. about 1.0%
zinc oxide b. about 0.5% zinc citrate c. about 1.5% L-arginine d.
about 1450 ppm sodium fluoride; e. about benzyl alcohol 0.1 wt. %
and f. about 5% small particle silica (e.g., AC43), based on the
total weight of the composition.
29. The oral care composition of claim 1 comprising: a. about 1.0%
zinc oxide b. about 0.5% zinc citrate c. about 5% L-arginine d.
about 1450 ppm sodium fluoride; and e. about 5% small particle
silica, (e.g., AC43), based on the total weight of the
composition.
30. The oral care composition of claim 1, wherein the oral
composition may be any of the following oral compositions selected
from the group consisting of: a toothpaste or a dentifrice, a
mouthwash or a mouth rinse, a topical oral gel, and a denture
cleanser.
31. The oral care composition of claim 1, wherein the composition
is obtained or obtainable by combining the ingredients as set forth
in claim 1.
32. A method to improve oral health comprising applying an
effective amount of the oral composition of claim 1 to the oral
cavity of a subject in need thereof, wherein the method is
effective 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 bio film 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, xiv. Whiten teeth, xv. reduce
erosion of the teeth, xvi. immunize (or protect) the teeth against
cariogenic bacteria and their effects, and/or xvii. clean the teeth
and oral cavity.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority to U.S.
provisional application 62/187,801, filed Jul. 1, 2015, the
contents of which are incorporated herein by reference in their
entirety.
FIELD
[0002] This invention relates to oral care compositions comprising
arginine or lysine or salt thereof, zinc oxide and zinc citrate,
and a fluoride source, as well as to methods of using and of making
these compositions.
BACKGROUND
[0003] Oral care compositions present particular challenges in
preventing microbial contamination. Arginine and other basic amino
acids have been proposed for use in oral care and are believed to
have significant benefits in combating cavity formation and tooth
sensitivity.
[0004] Commercially available arginine-based toothpaste contains
arginine bicarbonate and precipitated calcium carbonate, but not
fluoride. The carbonate ion is believed to have cariostatic
properties, and the calcium is believed to form a complex with
arginine to provide a protective effect.
[0005] However, the formulation of certain oral care compositions
presents special challenges. For example, oral care compositions
comprising arginine or basic amino acids may have a basic pH,
increasing potential for microbial contamination compared to acidic
formulations. Moreover, not all preservatives are active at higher
pH. Some preservatives negatively affect the taste or aesthetics of
the product. While certain preservatives, such as ethanol or
parabens, are known to be effective at a range of pHs, these
preservatives are not suitable for all products or all markets.
[0006] Zinc is a well-known antimicrobial agent used in toothpaste
compositions Zinc is also a well-known essential mineral for human
health, and has been reported to help strengthen dental enamel and
to promote cell repair. Unfortunately, conventional toothpaste
formulations often require a high concentrations of zinc, e.g., 2%
by weight or more, to achieve efficacy. At this concentration, the
zinc imparts a notably astringent taste to the composition. There
is thus a need for improved antibacterial toothpaste formulations
that do not suffer from the drawbacks of conventional
compositions.
[0007] Accordingly, there is a need for improved preservative
agents for use in oral compositions comprising basic amino
acids.
BRIEF SUMMARY
[0008] It has been surprisingly found that the inclusion of an
amino acid e.g., arginine or lysine, unexpectedly increase the
antibacterial effect of oral care compositions comprising a zinc
oxide and/or zinc citrate, selected at certain concentrations and
amounts in the oral cavity of a user. The formulations use
comparable amounts of zinc to what is found in current market
formulations. However, while comparable amounts of zinc are used in
the current invention (i.e., relative to various market
formulations), the amount of soluble zinc is believed to be
actually increased relative to various market formulations. Without
being bound by any theory, it is believed that the presence of the
amino acid may help to increase the amount of available soluble
zinc, which aids in delivery and inhibits bacterial growth in the
oral cavity of a user.
[0009] In one aspect the invention is an oral care composition
(Composition 1.0) comprising: [0010] a. A basic amino acid in free
or salt from, wherein the amino acid is selected from arginine,
lysine, and combinations thereof; (e.g., free form arginine) [0011]
b. zinc oxide and zinc citrate [0012] c. a fluoride source (e.g.,
sodium fluoride). For example, the invention contemplates any of
the following compositions (unless otherwise indicated, values are
given as percentage of the overall weight of the composition)
[0013] 1.1 Composition 1.0 wherein the basic amino acid has the
L-configuration (e.g., L-arginine). [0014] 1.2 Any of the preceding
compositions wherein the basic amino acid is arginine or lysine is
in free form. [0015] 1.3 Any of the preceding compositions wherein
the basic amino acid is provided in the form of a di- or
tri-peptide comprising arginine or lysine, or salts thereof. [0016]
1.4 Any of the preceding compositions wherein the basic amino acid
is arginine, and wherein the arginine is present in an amount
corresponding to 0.1% to 15%, e.g., 0.1 wt % to 10 wt %, e.g., 0.1
to 5 wt %, e.g., 0.5 wt % to 3 wt % of the total composition
weight, about e.g., 1%, 1.5%, 2%, 3%, 4%, 5%, or 8%, wherein the
weight of the basic amino acid is calculated as free form. [0017]
1.5 Any of the preceding compositions wherein the amino acid is
arginine from 0.1 wt. %-6.0 wt. %. (e.g., about 1.5 wt %). [0018]
1.6 Any of the preceding compositions wherein the amino acid is
arginine from about 1.5 wt. %. [0019] 1.7 Any of the preceding
compositions wherein the amino acid is arginine from 4.5 wt. % -8.5
wt. % (e.g., 5.0%). [0020] 1.8 Any of the preceding compositions
wherein the amino acid is arginine from about 5.0 wt. %. [0021] 1.9
Any of the preceding compositions wherein the amino acid is
arginine from 3.5 wt. %-9 wt. %. [0022] 1.10 Any of the preceding
compositions wherein the amino acid is arginine from about 8.0 wt.
%. [0023] 1.11 Any of the preceding compositions wherein the amino
acid is L-arginine. [0024] 1.12 Any of the preceding compositions
wherein the amino acid is free form arginine. [0025] 1.13 Any of
the preceding compositions wherein the basic amino acid is lysine
(e.g., 2% wt., 3% wt., 4% wt., 5% wt., 6% wt.), (e.g., 4% wt.).
[0026] 1.14 Any of the preceding compositions wherein the amino
acid is lysine from 1.0 wt. %-6.0 wt. %. [0027] 1.15 Any of the
preceding compositions wherein the amino acid is lysine from about
1.5 wt. %. [0028] 1.16 Any of the preceding compositions wherein
the amino acid is lysine from about 4.0 wt. %. [0029] 1.17 Any of
the preceding compositions wherein the amino acid is L-lysine.
[0030] 1.18 Any of the preceding compositions wherein the amino
acid is free form lysine. [0031] 1.19 Any of the preceding
compositions wherein the amino acid is arginine or lysine in
partially or wholly in salt form. [0032] 1.20 Composition 1.19
wherein the amino acid is arginine phosphate. [0033] 1.21
Composition 1.19 wherein the amino acid is arginine hydrochloride.
[0034] 1.22 Composition 1.19 wherein the amino acid is arginine
bicarbonate. [0035] 1.23 Composition 1.19 wherein the amino acid is
lysine phosphate. [0036] 1.24 Composition 1.19 wherein the amino
acid is lysine hydrochloride. [0037] 1.25 Composition 1.19 wherein
the amino acid is lysine bicarbonate. [0038] 1.26 Any of the
preceding compositions wherein the amino acid is arginine or lysine
ionized by neutralization with an acid or a salt of an acid. [0039]
1.27 Any of preceding compositions wherein the composition is
ethanol-free. [0040] 1.28 Any of the preceding compositions further
comprising a fluoride source 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
combinations thereof. [0041] 1.29 The composition of 1.28, wherein
the fluoride source is stannous fluoride. [0042] 1.30 Any of the
preceding compositions wherein the fluoride source is a
fluorophosphate. [0043] 1.31 Any of the preceding compositions
wherein the fluoride source is sodium monofluorophosphate. [0044]
1.32 The composition of 1.28, wherein the fluoride source is sodium
fluoride. [0045] 1.33 Any of the preceding compositions wherein the
fluoride source is a fluoride salt present in an amount of 0.1 wt.
% to 2 wt. % (0.1 wt %-0.6 wt. %) of the total composition weight
(e.g., sodium fluoride (e.g., about 0.32 wt. %) or sodium
monofluorophosphate). [0046] 1.34 Any of the preceding compositions
wherein the fluoride source is sodium fluoride in an amount about
0.32 wt. % based on the weight of the composition. [0047] 1.35 Any
of the preceding compositions wherein the fluoride source is a
soluble fluoride salt which provides fluoride ion in an amount of
from 50 to 25,000 ppm (e.g., 750-2000 ppm, e.g., 1000-1500 ppm,
e.g., about 1000 ppm, e.g., about 1450 ppm). [0048] 1.36 Any of the
preceding compositions wherein the fluoride source is sodium
fluoride which provides fluoride in an amount from 750-2000ppm
(e.g., about 1450 ppm). [0049] 1.37 Any of the preceding
compositions wherein the fluoride source is selected from sodium
fluoride and sodium monofluorophosphate and which provides fluoride
in an amount from 1000 ppm-1500 ppm. [0050] 1.38 Any of the
preceding compositions wherein the fluoride source is sodium
fluoride or sodium monofluorophosphate and which provides fluoride
in an amount of about 1450 ppm. [0051] 1.39 Any of the preceding
compositions wherein the pH is between 7.5 and 10.5, e.g., 9.0 to
10.0, e.g., 9.4. [0052] 1.40 Any of the preceding compositions
further comprising calcium carbonate. [0053] 1.41 The composition
of 1.39, wherein the calcium carbonate is a precipitated calcium
carbonate high absorption (e.g., 20% to 30% by weight of the
composition) (e.g., 25% precipitated calcium carbonate high
absorption). [0054] 1.42 The composition of 1.40, further
comprising a precipitated calcium carbonate-light (e.g., about 10%
precipitated calcium carbonate-light) (e.g., about 10% natural
calcium carbonate). [0055] 1.43 Any of the preceding compositions
further comprising an effective amount of one or more alkali
phosphate salts, e.g., sodium, potassium or calcium salts, e.g.,
selected from alkali dibasic phosphate and alkali pyrophosphate
salts, e.g., alkali phosphate salts selected from sodium phosphate
dibasic, potassium phosphate dibasic, dicalcium phosphate
dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate,
tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium
hydrogenorthophoshpate, monosodium phosphate, pentapotassium
triphosphate and mixtures of any of two or more of these, e.g., in
an amount of 0.01-20%, e.g., 0.1-8%, e.g., e.g., 0.1 to 5%, e.g.,
0.3 to 2%, e.g., 0.3 to 1%, e.g about 0.01%, about 0.1%, about
0.5%, about 1%, about 2%, about 5%, about 6%, by weight of the
composition. [0056] 1.44 Any of the preceding compositions
comprising tetrapotassium pyrophosphate, disodium
hydrogenorthophoshpate, monosodium phosphate, and pentapotassium
triphosphate. [0057] 1.45 Any of the preceding compositions
comprising a polyphosphate. [0058] 1.46 The composition of 1.44,
wherein the polyphosphate is tetrasodium pyrophosphate. [0059] 1.47
The composition of 1.45, wherein the tetrasodium pyrophosphate is
from 0.1-1.0 wt % (e.g., about 0.5 wt %). [0060] 1.48 Any of the
preceding compositions further comprising an abrasive or
particulate (e.g., silica). [0061] 1.49 Any of the preceding
compositions wherein the composition comprises from 5 to 25%
abrasive silica, e.g. from 10 to 20% abrasive silica, e.g., 5 wt %,
10 wt %, 15 wt %, 20 wt % or 25 wt % abrasive silica. [0062] 1.50
Any of the preceding compositions wherein the silica is synthetic
amorphous silica. (e.g., 1%-28% by wt.) (e.g., 8%-25% by wt.).
[0063] 1.51 Any of the preceding composition wherein the silica
abrasives are silica gels or precipitated amorphous silicas, e.g.
silicas having an average particle size ranging from 2.5 microns to
12 microns. [0064] 1.52 Any of the preceding compositions further
comprising a small particle silica having a median particle size
(d50) of 1-5 microns (e.g., 3-4 microns) (e.g., about 5 wt. %
Sorbosil AC43 from PQ Corporation, Warrington, United Kingdom).
[0065] 1.53 Any of the preceding compositions wherein 20-30 wt % of
the total silica in the composition is small particle silica (e.g.,
having a median particle size (d50) of 3-4 microns) and wherein the
small particle silica is about 5 wt. % of the oral care
composition. [0066] 1.54 Any of the preceding compositions
comprising silica wherein the silica is used as a thickening agent,
e.g., particle silica. [0067] 1.55 Any of the preceding
compositions further comprising a nonionic surfactant, wherein the
nonionic surfactant is in an amount of from 0.5-5%, e.g, 1-2%,
selected from poloxamers (e.g., poloxamer 407), polysorbates (e.g.,
polysorbate 20), polyoxyl hydrogenated castor oil (e.g., polyoxyl
40 hydrogenated castor oil), and mixtures thereof. [0068] 1.56 Any
of the preceding compositions, wherein the poloxamer nonionic
surfactant has a polyoxypropylene molecular mass (Mw) of from 3000
to 5000 g/mol and a polyoxyethylene content of from 60 to 80 mol %,
e.g., the poloxamer nonionic surfactant comprises poloxamer 407.
[0069] 1.57 Any of the preceding compositions further comprising
glycerin, wherein the glycerin is in a total amount of 25-40%
(e.g., about 35%). [0070] 1.58 The composition of 1.55, wherein the
glycerin is in an amount of about 35% by wt. of the composition.
[0071] 1.59 The composition of 1.55, wherein the glycerin is in an
amount of about 26% by wt. of the composition. [0072] 1.60 Any of
the preceding compositions further comprising sorbitol, wherein the
sorbitol is in a total amount of 10-40% (e.g., about 23%). [0073]
1.61 The composition of 1.57, wherein the sorbitol is in an amount
of about 13% by wt. of the composition. [0074] 1.62 The composition
of any of 1.57-1.59, wherein the glycerin is an amount of about 26%
by wt., and the sorbitol is in an amount of about 13% by wt. [0075]
1.63 Any of the preceding compositions, wherein the ratio of the
amount of zinc oxide (e.g., wt. %) to zinc citrate (e.g., wt %) is
from 1.5:1 to 4.5:1 (e.g., 2:1, 2.5:1, 3:1, 3.5:1, or 4:1). [0076]
1.64 Any of the preceding compositions, wherein the zinc citrate is
in an amount of from 0.25 to 1.0 wt % (e.g.,0.25 to 0.75 wt. %, or
0.5 wt. %) and zinc oxide may be present in an amount of from 0.75
to 1.25 wt % (e.g., 1.0 wt. %) based on the weight of the oral care
composition. [0077] 1.65 Any of the preceding compositions wherein
the zinc citrate is about 0.5 wt %. [0078] 1.66 Any of the
preceding compositions wherein the zinc oxide is about 1.0 wt %.
[0079] 1.67 Any of the preceding compositions where the zinc
citrate is about 0.5 wt % and the zinc oxide is about 1.0 wt %.
[0080] 1.68 Any of the preceding compositions further comprising an
additional ingredient selected from: benzyl alcohol,
Methylisothizolinone ("MIT"), Sodium bicarbonate, lauryl alcohol,
and polyphosphate. [0081] 1.69 Any of the preceding compositions
wherein the benzyl alcohol is present from 0.1-0.8 wt %., or 0.2 to
0.7 wt %, or from 0.3 to 0.6 wt %, or from 0.4 to 0.5 wt %, e.g.
about 0.1 wt. %, about 0.2 wt. %, about 0.3 wt %, about 0.4 wt %,
about 0.5 wt %, about 0.6 wt %, about 0.7 wt % or about 0.8 wt %.
[0082] 1.70 Any of the preceding compositions wherein the benzyl
alcohol is about 0.4 wt %. [0083] 1.71 Any of the preceding
compositions comprising polymer films. [0084] 1.72 Any of the
preceding compositions comprising flavoring, fragrance and/or
coloring. [0085] 1.73 The composition of 1.65, wherein the
flavoring agent is sodium saccharin, sucralose, or a mixture
thereof. [0086] 1.74 Any of the preceding compositions, wherein the
composition comprises a thickening agent selected from the group
consisting of carboxyvinyl polymers, carrageenan, xanthan,
hydroxyethyl cellulose and water soluble salts of cellulose ethers
(e.g., sodium carboxymethyl cellulose and sodium carboxymethyl
hydroxyethyl cellulose). [0087] 1.75 Any of the preceding
compositions, wherein the composition comprises sodium
carboxymethyl cellulose (e.g., from 0.5 wt. %-1.5 wt. %). [0088]
1.76 Any of the preceding compositions comprising from 5%-40%,
e.g., 10%-35%, e.g., about 15%, 25%, 30%, and 35% water. [0089]
1.77 Any of the preceding compositions comprising an additional
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, honokiol, catechol, methyl
salicylate, epigallocatechin gallate, epigallocatechin, gallic
acid, miswak extract, sea-buckthorn extract), bisguanide
antiseptics (e.g., chlorhexidine, alexidine or octenidine),
quaternary ammonium compounds (e.g., cetylpyridinium chloride
(CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC),
N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic
antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine,
delmopinol, salifluor, metal ions (e.g., zinc salts, for example,
Zinc Chloride, Zinc Lactate, Zinc Sulfate, 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. [0090] 1.78 Any of the preceding compositions comprising
an antioxidant, e.g., selected from the group consisting of
Co-enzyme Q10, PQQ, Vitamin C, Vitamin E, Vitamin A, BHT,
anethole-dithiothione, and mixtures thereof. [0091] 1.79 Any of the
preceding compositions comprising a whitening agent. [0092] 1.80
Any of the preceding compositions 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. [0093] 1.81
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. [0094]
1.82 Any of the preceding compositions further comprising an agent
that interferes with or prevents bacterial attachment, e.g., ethyl
lauroyl arginiate (ELA) or chitosan.
[0095] 1.83 Any of the preceding compositions comprising: [0096] a.
about 1.0% zinc oxide [0097] b. about 0.5% zinc citrate [0098] c.
about 1.5% L-arginine [0099] d. about 1450 ppm sodium fluoride;
[0100] e. about 0.1% benzyl alcohol and [0101] f. about 5% small
particle silica. [0102] 1.84 Any of the preceding compositions
comprising: [0103] a. about 1.0% zinc oxide [0104] b. about 0.5%
zinc citrate [0105] c. about 5% L-arginine [0106] d. about 1450 ppm
sodium fluoride; and [0107] e. about 5% small particle silica.
[0108] 1.85 Any of the preceding compositions comprising: [0109] a.
about 1.0% zinc oxide [0110] b. about 0.5% zinc citrate [0111] c.
about 5% L-arginine [0112] d. about 0.32% sodium fluoride; and
[0113] e. about 5% small particle silica. [0114] 1.86 Any of the
preceding compositions effective upon application to the oral
cavity, e.g., by rinsing, optionally in conjunction 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) prevents stains and/or 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. [0115] 1.87 Any of the
preceding oral compositions, wherein the oral composition may be
any of the following oral compositions selected from the group
consisting of: a toothpaste or a dentifrice, a mouthwash or a mouth
rinse, a topical oral gel, and a denture cleanser. [0116] 1.88 A
composition obtained or obtainable by combining the ingredients as
set forth in any of the preceding compositions.
[0117] A composition obtained or obtainable by combining the
ingredients as set forth in any of the preceding compositions.
[0118] A composition for use as set for in any of the preceding
compositions.
[0119] In another embodiment, the invention encompasses a method to
improve oral health comprising applying an effective amount of the
oral composition of any of the embodiments set forth above to the
oral cavity of a subject in need thereof, e.g., a method to [0120]
i. reduce or inhibit formation of dental caries, [0121] ii. reduce,
repair or inhibit early enamel lesions, e.g., as detected by
quantitative light-induced fluorescence (QLF) or electrical caries
measurement(ECM), [0122] iii. reduce or inhibit demineralization
and promote remineralization of the teeth, [0123] iv. reduce
hypersensitivity of the teeth, [0124] v. reduce or inhibit
gingivitis, [0125] vi. promote healing of sores or cuts in the
mouth, [0126] vii. reduce levels of acid producing bacteria, [0127]
viii. to increase relative levels of arginolytic bacteria, [0128]
ix. inhibit microbial bio film formation in the oral cavity, [0129]
x. raise and/or maintain plaque pH at levels of at least pH 5.5
following sugar challenge, [0130] xi. reduce plaque accumulation,
[0131] xii. treat dry mouth, [0132] xiii. enhance systemic health,
including cardiovascular health, e.g., by reducing potential for
systemic infection via the oral tissues, [0133] xiv. Whiten teeth,
[0134] xv. reduce erosion of the teeth, [0135] xvi. immunize (or
protect) the teeth against cariogenic bacteria and their effects,
and/or [0136] xvii. clean the teeth and oral cavity. The invention
further comprises the use of sodium bicarbonate, sodium methyl
cocoyl taurate (tauranol), MIT (methyl isothiazolinone), and benzyl
alcohol and combinations thereof in the manufacture of a
Composition of the Invention, e.g., for use in any of the
indications set forth in the above method of Composition 1.0, et
seq.
DETAILED DESCRIPTION
[0137] As used herein, the term "oral composition" means the total
composition that is delivered to the oral surfaces. The composition
is further defined as a product which, during the normal course of
usage, is not, the purpose of systemic administration of particular
therapeutic agents, intentionally swallowed, but is rather retained
in the oral cavity for a time sufficient to contact substantially
all of the dental surfaces and/or oral tissues for the purposes of
oral activity. Examples of such compositions include, but are not
limited to, toothpaste or a dentifrice, a mouthwash or a mouth
rinse, a topical oral gel, a denture cleanser, and the like.
[0138] As used herein, the term "dentifrice" means paste, gel, or
liquid formulations unless otherwise specified. The dentifrice
composition can be in any desired form such as deep striped,
surface striped, multi-layered, having the gel surrounding the
paste, or any combination thereof. Alternatively the oral
composition is provided as a dual phase composition, wherein
individual compositions are combined when dispensed from a
separated compartment dispenser.
Basic Amino Acids
[0139] 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 7 or greater.
[0140] Accordingly, basic amino acids include, but are not limited
to, arginine, lysine, serine, citrullene, ornithine, creatine,
histidine, diaminobutanoic acid, diaminoproprionic acid, salts
thereof or combinations thereof. In a particular embodiment, the
basic amino acids are selected from arginine, citrullene, and
ornithine.
[0141] In certain embodiments, the basic amino acid is arginine,
for example, L-arginine, or a salt thereof.
[0142] 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 which 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.
[0143] In certain embodiments, the basic amino acid is present in
an amount corresponding to 0.1% to 15%, e.g., 0.1 wt % to 10 wt %,
e.g., 0.1 to 5 wt %, e.g., 0.5 wt to 3 wt % of the total
composition weight, about e.g., 1%, 1.5%, 2%, 3%, 4%, 5%, or 8%,
wherein the weight of the basic amino acid is calculated as free
form.
Fluoride Ion Source
[0144] 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., each of
which are incorporated herein by reference. Representative fluoride
ion sources used with the present invention (e.g., Composition 1.0
et seq.) 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. Where the
formulation comprises calcium salts, the fluoride salts are
preferably salts wherein the fluoride is covalently bound to
another atom, e.g., as in sodium monofluorophosphate, rather than
merely ionically bound, e.g., as in sodium fluoride.
Surfactants
[0145] The invention may in some embodiments contain anionic
surfactants, e.g., the Compositions of Composition 1.0, et seq.,
for example, 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 cocoglyceride sulfate;
higher alkyl sulfates, such as sodium lauryl sulfate; higher
alkyl-ether sulfates, e.g., of formula
CH.sub.3(CH.sub.2).sub.mCH.sub.2(OCH.sub.2CH.sub.2).sub.nOS0.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, for example sodium laureth-2 sulfate
(CH.sub.3(CH2).sub.10CH.sub.2(OCH.sub.2CH.sub.2).sub.2OS0.sub.3Na);
higher alkyl aryl sulfonates such as sodium dodecyl benzene
sulfonate (sodium lauryl benzene sulfonate); 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. By "higher alkyl" is
meant, e.g., C.sub.6-3o alkyl. In particular embodiments, the
anionic surfactant (where present) is selected from sodium lauryl
sulfate and sodium ether lauryl sulfate. When present, the anionic
surfactant is present in an amount which is effective, e.g.,
>0.001% by weight of the formulation, but not at a concentration
which would be irritating to the oral tissue, e.g., 1%, and optimal
concentrations depend on the particular formulation and the
particular surfactant. In one embodiment, the anionic surfactant is
present at from 0.03% to 5% by weight, e.g., 1.5%.
[0146] 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 8 to 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. 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.
[0147] Illustrative nonionic surfactants of Composition 1.0, et
seq., 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. In a
particular embodiment, the composition of the invention comprises a
nonionic surfactant selected from polaxamers (e.g., polaxamer 407),
polysorbates (e.g., polysorbate 20), polyoxyl hydrogenated castor
oils (e.g., polyoxyl 40 hydrogenated castor oil), and mixtures
thereof.
[0148] Illustrative amphoteric surfactants of Composition 1.0, et
seq., that can be used in the compositions of the invention include
betaines (such as cocamidopropylbetaine), derivatives of aliphatic
secondary and tertiary amines in which the aliphatic radical can be
a straight or branched chain and wherein one of the aliphatic
substituents contains about 8-18 carbon atoms and one contains an
anionic water-solubilizing group (such as carboxylate, sulfonate,
sulfate, phosphate or phosphonate), and mixtures of such
materials.
[0149] The surfactant or mixtures of compatible surfactants can be
present in the compositions of the present invention in 0.1% to 5%,
in another embodiment 0.3% to 3% and in another embodiment 0.5% to
2% by weight of the total composition.
Flavoring Agents
[0150] 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 and various flavoring aldehydes, esters, alcohols, and similar
materials, as well as sweeteners such as sodium saccharin. 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.
[0151] The flavoring agent is incorporated in the oral composition
at a concentration of 0.01 to 2% by weight.
Chelating and Anti-Calculus agents
[0152] The oral care compositions of the invention also may 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.
[0153] Another group of agents suitable for use as chelating or
anti-calculus 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 0.1 wt. % pyrophosphate ions, e.g., 0.1 to 3 wt 5,
e.g., 0.1 to 2 wt %, e.g., 0.1 to 1 wt %, e.g., 0.2 to 0.5 wt %.
The pyrophosphates also contribute to preservation of the
compositions by lowering the effect of water activity.
Polymers
[0154] The oral care compositions of the invention also optionally
include one or more polymers, such as polyethylene glycols,
polyvinyl methyl 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. Certain embodiments include 1:4 to 4:1
copolymers of maleic anhydride or acid with another polymerizable
ethylenically unsaturated monomer, for example, methyl vinyl ether
(methoxyethylene) having a molecular weight (M.W.) of about 30,000
to about 1,000,000 (Mw). These copolymers are available for example
as Gantrez AN 139(M.W. 500,000), AN 1 19 (M.W. 250,000) and S-97
Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals
Corporation.
[0155] 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. 1 103, 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.
[0156] 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-chlorosorbic, 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.
[0157] 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.
[0158] 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.
[0159] 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, xanthan gum, 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. Silica may also be
available as a thickening agent, e.g., synthetic amorphous silica.
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. Thickeners may be present
in an amount of from 1 wt % to 15 wt %, from 3 wt % to 10 wt %, 4
wt % to 9 wt %, from 5 wt % to 8 wt %, for example 5 wt %, 6 wt %,
7 wt %, or 8 wt %.
Abrasives
[0160] Natural calcium carbonate is found in rocks such as chalk,
limestone, marble and travertine. It is also the principle
component of egg shells and the shells of mollusks. The natural
calcium carbonate abrasive of the invention is typically a finely
ground limestone which may optionally be refined or partially
refined to remove impurities. For use in the present invention, the
material has an average particle size of less than 10 microns,
e.g., 3-7 microns, e.g. about 5.5 microns. For example a small
particle silica may have an average particle size (D50) of 2.5-4.5
microns. Because natural calcium carbonate may contain a high
proportion of relatively large particles of not carefully
controlled, which may unacceptably increase the abrasivity,
preferably no more than 0.01%, preferably no more than 0.004% by
weight of particles would not pass through a 325 mesh. The material
has strong crystal structure, and is thus much harder and more
abrasive than precipitated calcium carbonate. The tap density for
the natural calcium carbonate is for example between 1 and 1.5
g/cc, e.g., about 1.2 for example about 1.19 g/cc. There are
different polymorphs of natural calcium carbonate, e.g., calcite,
aragonite and vaterite, calcite being preferred for purposes of
this invention. An example of a commercially available product
suitable for use in the present invention includes Vicron.RTM.
25-11 FG from GMZ.
[0161] Precipitated calcium carbonate is generally made by
calcining limestone, to make calcium oxide (lime), which can then
be converted back to calcium carbonate by reaction with carbon
dioxide in water. Precipitated calcium carbonate has a different
crystal structure from natural calcium carbonate. It is generally
more friable and more porous, thus having lower abrasivity and
higher water absorption. For use in the present invention, the
particles are small, e.g., having an average particle size of 1-5
microns, and e.g., no more than 0.1%, preferably no more than 0.05%
by weight of particles which would not pass through a 325 mesh. The
particles may for example have a D50 of 3-6 microns, for example
3.8-4.9, e.g., about 4.3; a D50 of 1-4 microns, e.g. 2.2-2.6
microns, e.g., about 2.4 microns, and a D10 of 1-2 microns, e.g.,
1.2-1.4, e.g. about 1.3 microns. The particles have relatively high
water absorption, e.g., at least 25 g/100g, e.g. 30-70 g/100g.
Examples of commercially available products suitable for use in the
present invention include, for example, Carbolag.RTM. 15 Plus from
Lagos Industria Quimica.
[0162] In certain embodiments the invention may comprise additional
calcium-containing abrasives, for example calcium phosphate
abrasive, e.g., tricalcium phosphate (Ca.sub.3(P0.sub.4).sub.2),
hydroxyapatite (Ca.sub.10(P0.sub.4).sub.6(OH).sub.2), or dicalcium
phosphate dihydrate (CaHP0.sub.4.2H.sub.20, also sometimes referred
to herein as DiCal) or calcium pyrophosphate, and/or silica
abrasives, sodium metaphosphate, potassium metaphosphate, aluminum
silicate, calcined alumina, bentonite or other siliceous materials,
or combinations thereof.
[0163] In certain embodiments, the composition may comprise an
abrasive silica. Any silica suitable for oral care compositions may
be used, such as small particle silica, precipitated silicas, or
prophy silicas.
[0164] For example, the silica can also be small particle silica
(e.g., Sorbosil AC43 from PQ, Warrington, United Kingdom). The
composition preferable contains from 5 to 20 wt % small particle
silica, or for example 10-15 wt %, or for example 5 wt %, 10 wt %,
15 wt % or 20 wt % small particle silica.
[0165] In another embodiment, the abrasive may be high cleaning
precipitated silica having a pellicle cleaning ratio (PCR) of
greater than 85 when tested at 20% loading is known in the art as
high cleaning silica. Typically, high cleaning silica also has a
mean particle size d.sub.50 of from 5 to 15 .mu.m and an oil
absorption of from 40 to 120 cm.sup.3/100g silica. The cleaning
efficacy of the precipitated silica is expressed using the pellicle
cleaning ratio (PCR). This is typically measured at 20% silica
loading. The high cleaning silica preferably has a PCR value of
greater than 85. The efficacy of the precipitated silica can also
be expressed with reference to its abrasive characteristic using
the radioactive dentin abrasion (RDA). Ideally, RDA values for an
oral composition should be below about 250 to protect tooth
enamel/dentin. Methods of performing PCR and RDA are described in
e.g., U.S. Pat. Nos. 5,939,051 and 6,290,933 and "In Vitro Removal
of Stain With Dentifrice", G. K. Stookey et al., J. Dental
Research, Vol. 61, pages 1236-9, November 1982." Typically, the
precipitated silica has a mean particle size d.sub.50 of from 5 to
15 .mu.m and an oil absorption of from 40 to 120 cm.sup.3/100 g
silica. Examples of precipitated silica having a mean particle size
d.sub.50 of from 5 to 15 .mu.m and an oil absorption of from 40 to
120 cm.sup.3/100 g silica including commercially available silicas
such as Zeodent.degree. 103 and Zeodent.degree. 105 (Huber Silica
Americas).
[0166] The composition preferable contains from 5 to 20 wt % high
cleaning precipitated silica, or for example 10-15 wt %, or for
example 5 wt %, 10 wt %, 15 wt % or 20 wt % high cleaning
precipitated silica.
[0167] The composition may also comprise an abrasive silica having
an acid pH in the composition. For example, prophy silica available
from Grace, offered as Sylodent.TM., can be used. The acidic silica
abrasive is included in the dentifrice components at a
concentration of about 2 to about 35% by weight; about 3 to about
20% by weight, about 3 to about 15% by weight, about 10 to about
15% by weight. For example, the acidic silica abrasive may be
present in an amount selected from 2 wt. %, 3wt. %, 4% wt. %, 5 wt.
%, 6 wt. %, 7 wt. %, 8 wt. %, 9 wt. %, 10 wt. %, 11 wt. %, 12 wt.
%, 13 wt. %, 14 wt. %,15 wt. %, 16 wt. %, 17 wt. %, 18 wt. %, 19
wt. %, 20 wt. %.
[0168] A commercially available acidic silica abrasive is Sylodent
783 available from W. R. Grace & Company, Baltimore, Md.
Sylodent 783 has a pH of 3.4-4.2 when measured as a 5% by weight
slurry in water. For use in the present invention, the silica
material has an average particle size of less than 10 microns,
e.g., 3-7 microns, e.g. about 5.5 microns.
Water
[0169] Water is 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 5% to 45%,
e.g., 10% to 20%, e.g., 25-35%, 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 silica or any components of the invention. The Karl
Fischer method is a one measure of calculating free water.
Humectants
[0170] Within certain embodiments of the oral compositions, it is
also desirable to incorporate a humectant to reduce evaporation and
also contribute towards preservation by lowering water activity.
Certain humectants can also impart desirable sweetness or flavor to
the compositions. The humectant, on a pure humectant basis,
generally includes 15% to 70% in one embodiment or 30% to 65% in
another embodiment by weight of the composition.
[0171] 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 compositions herein.
pH Adjusting Agents
[0172] In some embodiments, the compositions of the present
disclosure contain a buffering agent. Examples of buffering agents
include anhydrous carbonates such as sodium carbonate,
sesquicarbonates, bicarbonates such as sodium bicarbonate,
silicates, bisulfates, phosphates (e.g., monopotassium phosphate,
monosodium phosphate, disodium phosphate, dipotassium phosphate,
tribasic sodium phosphate, sodium tripolyphosphate, pentapotassium
tripolyphosphate, phosphoric acid), citrates (e.g. citric acid,
trisodium citrate dehydrate), pyrophosphates (sodium and potassium
salts, e.g., tetrapotassium pyrophosphate) and combinations
thereof. The amount of buffering agent is sufficient to provide a
pH of about 5 to about 9, preferable about 6 to about 8, and more
preferable about 7, when the composition is dissolved in water, a
mouthrinse base, or a toothpaste base. Typical amounts of buffering
agent are about 5% to about 35%, in one embodiment about 10% to
about 30%, in another embodiment about 15% to about 25%, by weight
of the total composition.
[0173] The present invention in its method aspect involves applying
to the oral cavity a safe and effective amount of the compositions
described herein.
[0174] The compositions and methods according to the invention
(e.g., Composition 1.0 et seq) 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.
[0175] 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.
[0176] 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.
EXAMPLE 1
Biofilm Model
[0177] The active-attachment biofilm model has been previously
described by Extercate et al. Caries Research 2010; 44: 372-379,
the contents of which are incorporated by reference herein. The
biofilm model consists of a metal lid with 24 clamps carrying
hydroxyapatite (HAP) disks. The model is inoculated in 24-well
plates with native saliva. Biofilms were formed via active
recruitment of bacteria onto free-hanging HAP disks.
[0178] Treatment is performed after formation of a 24 h biofilm.
Lactic acid production is determined to assess the residual
metabolic activity of biofilms after repeated exposure to test
products. The assay is conducted using a L-Lactate Assay Kit
according to the manufacturer's protocol (Cayman Chemical Company,
Cat. No. 700510).
[0179] Colony forming units (CFUs) are determined to assess the
anti-bacterial efficacy of test solutions after repeated exposure
to biofilms. HAP disks are removed from the lid and transferred to
1.5 ml CPW for sonication. CFUs are determined by colony counting.
Statistical analysis was performed using Minitab 16 Software. ANOVA
and Tukey test were performed on available CFU counts and lactic
acid values.
EXAMPLE 2
[0180] Anti-bacterial efficacy of arginine alone and in combination
with zinc in solutions and in toothpastes is tested by live counts
using the biofilm model described in Example 1. The approximate
number of live counts (CFUs) are as follows:
TABLE-US-00001 Toothpaste CFU/ml 8% arginine, 1.0% zinc oxide 9.0
and 0.5% zinc citrate 1.0% zinc oxide and 0.5% zinc 9.25 citrate,
and no arginine 8% arginine, and no zinc 9.60 citrate or zinc oxide
Placebo (no arginine, no zinc) 9.83 8% arginine, 1.0% zinc oxide
9.16 and 0.5% zinc citrate, tauronal
[0181] The number of live counts in the (solution) groups which
contain:
TABLE-US-00002 Solution CFU/ml 4% arginine, 0.5% zinc oxide 6.84
and 0.25% zinc citrate 0.5% zinc oxide and 0.25% zinc 7.50 citrate,
but which do not contain arginine 4% arginine, and no zinc citrate
10.0 or zinc oxide 0.5% zinc oxide 9.65 0.25% zinc citrate 9.55
Media 9.76
[0182] The above demonstrates the surprising effect which results
from the complex of arginine, zinc oxide, and zinc citrate.
[0183] While the above arginine/zinc complex groups show a lower
number of live counts (e.g., CFUs) compared to the zinc groups
(which did not include arginine), both groups demonstrate a
decreased number of CFUs relative to toothpaste and solution groups
which contain arginine (4% solution, 8% toothpaste, which did not
include zinc), zinc oxide (0.5% solution, 1.0% toothpaste, which
did not include arginine or zinc citrate) and zinc citrate (0.25%
solution, 0.5% toothpaste, which did not include arginine or zinc
oxide) and control.
[0184] Groups (toothpastes and solutions) with arginine only (not
together with zinc) are not decreased in the number of live counts
relative to control groups.
EXAMPLE 3
[0185] The anti-metabolic activity of arginine alone and combined
with zinc on bacteria in solutions and in toothpastes is measured
by lactic acid production during a 3-hour window after the last
treatment. The bacterial metabolic activity, as measured by lactic
acid production, decreases in (toothpaste) groups with:
TABLE-US-00003 Toothpaste Lactate mM 8% arginine, 1.0% zinc oxide
1.75 and 0.5% zinc citrate 1.0% zinc oxide and 0.5% zinc 1.5
citrate, and no arginine 8% arginine, and no zinc 2.5 citrate or
zinc oxide Placebo (no arginine, no zinc) 2.5 8% arginine, 1.0%
zinc oxide 1.75 and 0.5% zinc citrate, tauronal
[0186] The decrease in the metabolic activity is relative to
control, as well as toothpastes which employ arginine only (which
did not include zinc), toothpastes which employ 0.5% zinc oxide
only, and toothpastes which employ 0.25% zinc citrate only.
[0187] The bacterial metabolic activity, as measured by lactic acid
production (solution) :
TABLE-US-00004 Solution Lactate mM 4% arginine, 0.5% zinc oxide 1.0
and 0.25% zinc citrate 0.5% zinc oxide and 0.25% zinc 1.0 citrate,
but which do not contain arginine 4% arginine, and no zinc citrate
3.9 or zinc oxide 0.5% zinc oxide 6.25 0.25% zinc citrate 6.0 Media
2.25
Groups (toothpastes and solutions) with arginine only (which did
not include zinc) do not show a decrease in metabolic activity
relative to control or placebo groups.
EXAMPLE 4
[0188] The antibacterial activity of serine and lysine is assessed
individually and in combination with zinc and determined by lactic
acid production during a 3-hour window after the last treatment
according to Example 1.
TABLE-US-00005 Solutions Log CFU/ml Negative control (water) 9.47
0.5% zinc oxide and 0.25% zinc 6.80 citrate 0.5% zinc oxide and
0.25% zinc 7.15 citrate, 4% serine 4% serine 9.45 0.5% zinc oxide
and 0.25% zinc 6.23 citrate, 4% lysine 4% lysine 9.37
[0189] The groups (solutions) with 4% serine (not together with
zinc) and 4% lysine (not complexed with zinc), do not demonstrate a
decrease in the number of CFUs relative to control solutions
(water).
[0190] However, groups (solutions) containing 4% lysine, 0.5% zinc
oxide and 0.25% zinc citrate, are decreased relative to control and
variable groups.
[0191] Groups with: 4% serine, 0.5% zinc oxide and 0.25% zinc
citrate, do not demonstrate a decrease in CFU counts relative to
control or variable (solutions) groups.
EXAMPLE 5
[0192] The anti-metabolic activity of serine and lysine
individually, and in combination with zinc, are tested. Using the
biofilm model described in Example 1, antibacterial activity of
serine and lysine is tested individually and in combination with
zinc. The groups with 4% serine and 4% lysine alone (which did not
include zinc) do not demonstrate a decrease in metabolic activity
relative to control solutions.
TABLE-US-00006 Solutions Lactate mM Negative control (water) 2.7
0.5% zinc oxide and 0.25% zinc 0.70 citrate 0.5% zinc oxide and
0.25% zinc 3.7 citrate, 4% serine 4% serine 2.4 0.5% zinc oxide and
0.25% zinc less than 0.5 citrate, 4% lysine 4% lysine 2.7
[0193] Groups containing: 4% lysine, 0.5% zinc oxide and 0.25% zinc
citrate, exhibit decreased metabolic activity relative to control
groups (water) and variable groups.
[0194] Groups with 4% serine, complexed with 0.5% zinc oxide and
0.25% zinc citrate, do not exhibit a decrease in metabolic activity
relative to control or variable groups
EXAMPLE 6
[0195] Tables 1 and 2 demonstrate that the amount of soluble zinc
in solution is increased in the presence of arginine, serine, and
lysine.
TABLE-US-00007 TABLE 1 Solubility of zinc salts in presence of
serine or lysine. Soluble Zn (%) = R*M2/(10*M1) M1 M2 R Sol. % sol.
Sample (mg) (g) (ppm) Zn (abs.) Zn (rel) Water NA NA NA NA NA 0.5%
Zinc 99 14.540 7.800 0.114558 23.9% Oxide + 0.25% Zinc Citrate (pH
6.95) 4% Serine + NA NA NA 0.479741 100% 0.5% zinc oxide + 0.25%
zinc citrate (pH 6.67) 4% Serine NA NA NA NA NA (pH 5.8) 4% Lysine
+ NA NA NA 0.479741 100% 0.5% Zinc Oxide + 0.25% Zinc Citrate (pH
6.99) 4% Lysine NA NA NA NA NA (pH 5.6)
TABLE-US-00008 TABLE 2 Solubility of zinc in presence of arginine,
lysine or serine. Simple Solutions Relative Soluble Zinc ZnO +
ZnCit (pH 6.8) 24% ZnO + ZnCit (pH 10.6*) 3% Arg + ZnO + ZnCit (pH
10.7) 19% Lys + ZnO + ZnCit (pH 6.8) 100% Ser + ZnO + ZnCit (pH
6.6) 100%
EXAMPLE 7
TABLE-US-00009 [0196] Description Compound I Humectants 20.0-25.0
Nonionic Surfactant 1.0-2.0 Amphoteric Surfactant 3.0-4.0
Flavoring/Fragrance/Coloring Agent 2.0-3.0 Polymers 10.0-15.0 pH
Adjusting Agents 1.5-3.0 Precipitated Calcium Carbonate 35.0 Zinc
Citrate Trihydrate 0.5 Zinc Oxide 1.0 Sodium Fluoride-USP, EP 0.32
Arginine Bicarbonate 13.86 Demineralized Water q.s.
EXAMPLE 8
Dentifrice Formulations
TABLE-US-00010 [0197] Compound Compound Compound Compound
Description A B C D Humectants 25.0-40.0 25.0-40.0 25.0-40.0
25.0-40.0 Anionic Surfactant 1.0-3.0 1.0-3.0 1.0-3.0 1.0-3.0
Flavoring/Fragrance/ 2.5-4.0 2.5-4.0 2.5-4.0 2.5-4.0 Coloring Agent
Polymers 4.0-6.0 4.0-6.0 4.0-6.0 4.0-6.0 pH Adjusting Agents
5.0-6.0 5.0-6.0 5.0-6.0 5.0-6.0 Synthetic Amorphous 16.0 21.37
17.92 7.81 Precipitated Silica Alumina 0.02 0.01 0.01 0.01 Silica
-- -- -- 15.0 Lauryl Alcohol 0.02 0.02 0.02 0.02 Zinc Citrate 0.5
0.5 0.5 0.5 Zinc Oxide 1.0 1.0 1.0 1.0 Sodium Fluoride-USP, EP 0.32
0.32 0.32 0.32 L-Arginine 5.0 5.0 5.0 5.0 Demineralized Water q.s.
q.s. q.s. q.s. Total Amount 100% 100% 100% 100% Impurities in the
Compounds above are present in less than 1.0 wt. %.
EXAMPLE 9
Dentifrice Formulations
TABLE-US-00011 [0198] Description Compound E Compound F Compound G
Humectants 25.0-40.0 25.0-40.0 25.0-40.0 Anionic Surfactant 1.0-3.0
1.0-3.0 1.0-3.0 Nonionic Surfactant 0.1-1.0 0.1-1.0 0.1-1.0
Amphoteric Surfactant 0.1-1.0 0.1-1.0 0.1-1.0 Flavoring/Fragrance/
4.0-6.0 4.0-6.0 4.0-6.0 Coloring Agent Polymers 0.1-2.0 0.1-2.0
0.1-2.0 pH Adjusting Agents 0.1-2.0 0.1-2.0 0.1-2.0 Thickener 6.0
6.5 7.0 Alumina 0.1 0.1 0.1 Synthetic Amorphous 17.6 8.8 22.4
Precipitate Silica Silica -- 15.0 -- Benzyl Alcohol 0.1 0.1 0.1
Synthetic Amorphous Silica 5.0 5.0 5.0 Zinc Citrate 0.5 0.5 0.5
Zinc Oxide 1.0 1.0 1.0 Sodium Fluoride-USP, EP 0.32 0.32 0.32
L-Arginine 1.5 1.5 1.5 Demineralized Water q.s. q.s. q.s. Total
Amount 100% 100% 100% Impurities in the Compounds above are present
in less than 1.0 wt. %.
EXAMPLE 10
TABLE-US-00012 [0199] Description Compound H Humectants 45.0-55.0
Abrasives 14.0-16.0 Anionic Surfactant 1.0-3.0 Nonionic Surfactant
0.1-1.0 Amphoteric Surfactant 1.0-2.0 Flavoring/Fragrance/Coloring
Agent 1.0-3.0 Polymers 0.1-2.0 pH Adjusting Agents 0.1-2.0 Silica
Thickener 5.0 Benzyl Alcohol 0.1 Zinc Citrate Trihydrate 0.5 Zinc
Oxide 1.0 Sodium Fluoride-USP, EP 0.32 L-Arginine 1.5 Demineralized
Water q.s. *Note the above "Demineralized water" represents the
amount of free water (i.e., without calculating the amount of water
associated with silica and/or other ingredients)
EXAMPLE 11
TABLE-US-00013 [0200] Description Compound I Humectants 35.0-45.0
Abrasives 9.0-11.0 Anionic Surfactant 1.0-3.0
Flavoring/Fragrance/Coloring Agent 2.0-4.0 Polymers 3.0-8.0 pH
Adjusting Agents 4.0-8.0 Silica Thickener 5.0-10.0 Zinc Citrate
Trihydrate 0.5 Zinc Oxide 1.0 Sodium Fluoride-USP, EP 0.32
L-Arginine 5.0 Demineralized Water q.s. *Note the above
"Demineralized water" represents the amount of free water (i.e.,
without calculating the amount of water associated with silica
and/or other ingredients)
EXAMPLE 12
TABLE-US-00014 [0201] Description Compound J Compound K Compound L
Humectants 20.0-50.0 20.0-50.0 20.0-50.0 Abrasives 5.0-20.0
5.0-20.0 5.0-20.0 Anionic Surfactant 0.1-3.0 0.1-3.0 0.1-3.0
Nonionic Surfactant 0.1-1.0 0.1-1.0 0.1-1.0 Amphoteric Surfactant
0.1-2.0 0.1-2.0 0.1-2.0 Flavoring/Fragrance/ 0.1-5.0 0.1-5.0
0.1-5.0 Coloring Agent Polymers 0.1-2.0 0.1-2.0 0.1-2.0 pH
Adjusting Agents 0.1-2.0 0.1-2.0 0.1-2.0 Thickener 6.0 6.5 7.0
Dental Type Silica -- -- 15.0 High Cleaning Silica -- 15.0 --
Synthetic Abrasive Silica 10.0 -- -- Synthetic Amorphous Silica 5.0
5.0 5.0 Benzyl Alcohol 0.4 0.4 0.4 Synthetic Amorphous Silica 5.0
5.0 5.0 Zinc Citrate Trihydrate 0.5 0.5 0.5 Zinc Oxide 1.0 1.0 1.0
SodiumFluoride-USP, EP 0.32 0.32 0.32 L-Arginine 1.5 1.5 1.5
Demineralized Water q.s. q.s. q.s. *Note the above "Demineralized
water" represents the amount of free water (i.e., without
calculating the amount of water associated with silica and/or other
ingredients)
EXAMPLE 13
[0202] In one representative formulation, a dentifrice comprises
the following: [0203] a. 1.0 wt. % zinc oxide [0204] b. 0.5 wt. %
zinc citrate [0205] c. 1.5 wt. % or 5.0 wt. % L-arginine [0206] d.
about 1450 ppm sodium fluoride; and [0207] e. about 5 wt. % small
particle silica (e.g., AC43) Wherein the dentifrice is expected to
reduce erosion and reduce hypersensitivity in the mouth.
[0208] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
referenced in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls.
[0209] Unless otherwise specified, all percentages and amounts
expressed herein and elsewhere in the specification should be
understood to refer to percentages by weight. The amounts given are
based on the active weight of the material.
[0210] While the present invention has been described with
reference to embodiments, it will be understood by those skilled in
the art that various modifications and variations may be made
therein without departing from the scope of the present invention
as defined by the appended claims.
* * * * *