U.S. patent application number 09/772729 was filed with the patent office on 2001-07-05 for oral care compositions comprising chlorite and methods.
Invention is credited to Wimalasena, Rohan Lalith, Witt, Jonathan James, Wong, Andrew Lee.
Application Number | 20010006624 09/772729 |
Document ID | / |
Family ID | 21863828 |
Filed Date | 2001-07-05 |
United States Patent
Application |
20010006624 |
Kind Code |
A1 |
Witt, Jonathan James ; et
al. |
July 5, 2001 |
Oral care compositions comprising chlorite and methods
Abstract
The present invention relates to oral care compositions,
including therapeutic rinses, especially mouth rinses, as well as
toothpastes, gels, tooth powders, chewing gums, mouth sprays, and
lozenges (including breath mints), comprising at least a minimally
effective amount of chlorite ion, wherein preferably the pH of the
final composition is greater than 7 and level of chlorine dioxide
or chlorous acid is less than about 50 ppm, preferably is
essentially free of chlorine dioxide or chlorous acid. This
invention fuirther relates to a method for treating or preventing
gingivitis, plaque, periodontal disease, and/or breath malodor,
and/or for the whitening of teeth, in humans or other animals, by
applying a safe and effective amount of the chlorite ion
composition to the oral cavity.
Inventors: |
Witt, Jonathan James;
(Cincinnati, OH) ; Wimalasena, Rohan Lalith;
(Liberty Township, OH) ; Wong, Andrew Lee; (West
Chester, OH) |
Correspondence
Address: |
Emelyn L. Hiland
The Procter & Gamble Company
Health Care Research Center (Box 1050)
P.O. Box 8006
Mason
OH
45040-8006
US
|
Family ID: |
21863828 |
Appl. No.: |
09/772729 |
Filed: |
January 30, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09772729 |
Jan 30, 2001 |
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09032234 |
Feb 27, 1998 |
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6132702 |
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Current U.S.
Class: |
424/53 |
Current CPC
Class: |
A61K 8/20 20130101; A61Q
11/00 20130101 |
Class at
Publication: |
424/53 |
International
Class: |
A61K 007/20 |
Claims
What is claimed is:
1. An oral care mouthrinse composition comprising: (a) greater than
about 0.04%, by weight of the final composition, of chlorite ion
from chlorite salts; and (b) a pharmaceutically-acceptable topical,
mouthrinse oral carrier; wherein the final composition is
essentially free of chlorine dioxide or chlorous acid and the pH of
the final composition is greater than 7.0.
2. The composition of claim 1 wherein the composition comprises a
first and a second phase: (a) the first phase comprising chlorite
ion; and (b) the second phase comprising a
pharmaceutically-acceptable topical, oral carrier and comprising no
chlorite ion.
3. The composition of claim 2 wherein the composition comprises
greater than about 0.075%, by weight of the composition, of
chlorite ion.
4. The composition of claim 3 wherein the composition comprises
greater than about 0.15%, by weight of the composition, of chlorite
ion.
5. The composition of claim 2 wherein the level of chlorine dioxide
or chlorous acid in the final composition is less than about 5
ppm.
6. The composition of claim 5 wherein the level of chlorine dioxide
or chlorous acid in the final composition is less than about 1
ppm.
7. The composition of claim 2 wherein the pH is greater than
7.5.
8. The composition of claim 7 wherein the pH is from about 8 to
about 12.
9. The composition of claim 8 wherein the pH is from 8 to 10.
10. An oral care mouthrinse composition comprising: (a) greater
than about 0.04%, by weight of the final composition, of chlorite
ion from chlorite salts; and (b) a pharmaceutically-acceptable
topical, mouthwash oral carrier; wherein the pH of the final
composition is greater than 7.5 and wherein the level of chlorine
dioxide or chlorous acid in the composition is less than about 50
ppm.
11. An oral care mouthrinse composition according to claim 10
comprising a first and a second phase: (a) the first phase
comprising chlorite ion; and (b) the second phase comprising a
pharmaceutically-acceptable topical, oral carrier and comprising no
chlorite ion.
12. The composition of claim 11 wherein the composition comprises
greater than about 0.075%, by weight of the composition, of
chlorite ion.
13. The composition of claim 12 wherein the composition comprises
greater than about 0.15%, by weight of the composition, of chlorite
ion.
14. The composition of claim 13 wherein the level of chlorine
dioxide or chlorous acid in the final composition is less than
about 25 ppm.
15. The composition of claim 14 wherein the level of chlorine
dioxide or chlorous acid in the final composition is less than
about 15 ppm.
16. The composition of claim 15 wherein the level of chlorine
dioxide or chlorous acid in the final composition is less than
about 10 ppm.
17. The composition of claim 16 wherein the final composition is
essentially free of chlorine dioxide or chlorous acid.
18. The composition of claim 11 wherein the pH is greater than
7.6.
19. The composition of claim 18 wherein the pH is from about 8 to
about 12.
20. The composition of claim 19 wherein the pH is from 8 to 10.
21. A method for the treatment or prevention of periodontal
disease, plaque, and gingivitis, comprising the step of
administering to a subject's oral cavity, an oral care mouthrinse
composition according to claim 1 or claim 2.
23. A method for the treatment or prevention of periodontal
disease, plaque, and gingivitis, comprising the step of
administering to a subject's oral cavity, an oral care mouthrinse
composition according to claim 10 or claim 11.
24. A method for the treatment or prevention of breath malodor,
comprising the step of administering to a subject's oral cavity, an
oral care mouthrinse composition according to claim 1 or claim
2.
25. A method for the treatment or prevention of breath malodor,
comprising the step of administering to a subject's oral cavity, an
oral care mouthrinse composition according to claim 10 or claim
11.
26. A method for whitening teeth, comprising the step of
administering to a subject's oral cavity, an oral care mouthrinse
composition according to claim 1 or claim 2.
27. A method for whitening teeth, comprising the step of
administering to a subject's oral cavity, an oral care mouthrinse
composition according to claim 10 or claim 11.
Description
TECHNICAL FIELD
[0001] The present invention relates to oral care compositions,
including therapeutic rinses, especially mouth rinses, as well as
toothpastes, tooth gels, tooth powders, chewing gums, mouth sprays,
and lozenges (including breath mints), comprising an effective
amount of chlorite ion. This invention further relates to a method
for treating or preventing conditions of the oral cavity, such as
gingivitis, plaque, periodontal disease, and/or breath malodor, as
well as to a method for whitening teeth, in humans or other
animals.
BACKGROUND ART
[0002] Oral malodor, plaque, gingivitis, periodontal disease, and
discoloration of the teeth, are all undesirable conditions that
affect many people. First malodor of the oral cavity is also known
as halitosis or bad breath. It is broadly estimated in the US. that
20-90 million individuals have oral malodor. It is generally
believed that the cause of this condition is due to the presence of
anaerobic bacteria, especially gram-negative anaerobic bacteria, in
the mouth. These bacteria will generate volatile sulfur compounds
(VSC) which are known to cause breath malodor.
[0003] It is recognized in the art that some breath malodor is
caused by three chemical compounds. Specifically, these compounds
are hydrogen sulfide (H--S--H), methyl mercaptan (CH.sub.3--S--H)
and dimethyl sulfide (CH.sub.2--S--CH.sub.3). These compounds
result from the degradation of epithelial cells and bacteria in the
oral cavity. Specifically, the polypeptide chains of the epithelial
cell walls, are composed of a series of amino acids including
cysteine and methionine which contain sulfur side chains. The death
of microorganisms or epithelial cells results in degradation of the
polypeptide chains into their amino acid components, especially
cysteine and methionine. Cysteine and methionine are precursors to
the formation of VSC.
[0004] It is also recognized in the art that oral malodor not only
comes from the posterior dorsal surface of the tongue but also from
periodontal pockets. Furthermore, a person with gingivitis or
periodontal disease may have increased oral malodor from
disintegrated epithelial cells. Epithelial cells turn over faster
if inflammation is present. Therefore, a larger number of these
dead epithelial cells remain in the oral cavity and will degrade
into the malodorous compounds.
[0005] In addition VSC will also alter the epithelial barrier,
permitting penetration of the barrier by antigenic substances. For
example, VSC such as hydrogen sulfide, methyl mercaptan and
dimethyl sulfide contribute to the penetration of bacterial toxins
through the epithelial barrier into the underlying basal lamina and
connective tissue. A. Rizzo, Peridontics, 5: 233-236 (1967); W. Ng
and J. Tonzetich, J. Dental Research, 63(7): 994-997 (1984); M. C.
Solis-Gaffar, T. J. Fischer and A. Gaffar, J. Soc. Cosmetic Chem.,
30: 241-247 (1979). Thereafter, bacterial toxins, bacteria and
virus can invade the underlying gingival tissue adjacent to the
sulcular space, thereafter invading the underlying connective
tissue. A decrease in VSC will decrease the tissue permeability to
oral toxins and bacteria.
[0006] Systemic entities can contribute to oral malodor as well.
These entities include oral carcinomas, diabetes, liver and kidney
abnormalities, medications which change the oral environment, ENT
problems such as chronic sinusitis, tonsillitis and inflamed
adenoids. Gastrointestinal problems do not contribute to chronic
oral malodor, although this is a common belief. Evaluation and
diagnosis of oral malodor can be achieved with the Halimeter
(Interscan). The Halimeter is a gas-analysis sensor that measures
the volatile sulfur compounds in breath.
[0007] Furthermore, periodontal disease is also an undesirable
condition which has widespread occurrence. Periodontal disease is a
major cause of tooth loss in adults, beginning as early as age 12.
Even by age 15, it is possible that 4 out of 5 persons already have
gingivitis and possibly as many as 4 out of 10 have
periodontitis.
[0008] Periodontal disease affects the periodontum, which is the
investing and supporting tissues surrounding a tooth (i.e., the
periodontal ligament, the gingiva, and the alveolar bone).
Gingivitis and periodontitis are inflammatory disorders of the
gingiva and the deeper periodontal tissues, respectively.
[0009] It is well accepted that periodontal disease is associated
with the accumulation of plaque on the teeth. The teeth are coated
with a salivary proteanaceous material (pellicle) and thereafter
streptococci adhere to this coating. Gingivitis occurs from the
dental plaque, and periodontitis is caused by the infection
spreading to the periodontal pocket or space between the gingiva
and the tooth root.
[0010] Furthermore, consumers are very interested in making their
teeth whiter. Consumers consider people with whiter teeth as having
more personal confidence and better social acceptance.
[0011] Teeth comprise both an inner dentin layer and an outer hard
enamel layer. The enamel layer protects the inner dentin layer and
live tissue and serves as the contact surface for mastication of
solid food. The enamel layer is generally translucent and slightly
off-white in color. It is also considered porous since the hydroxy
apatite crystals that comprise the enamel form microscopic
hexagonal rods or prisms having microscopic pores or channels
between them. As a result of this porous structure, staining agents
and discoloring substances, such as antibiotics, foods containing
coloring materials, coffee, cola, tea, tabacco, etc., can permeate
the enamel and change its surface to appear yellow or brownish in
color.
[0012] While good oral hygiene, as achieved by brushing the teeth
with a cleansing dentifrice, may help reduce the incidence of
stain, gingivitis, plaque, periodontal disease, and/or breath
malodor, it does not necessarily prevent or eliminate their
occurrence. Microorganisms contribute to both the initiation and
progression of gingivitis, plaque, periodontal disease, and/or
breath malodor. Thus, in order to prevent or treat these
conditions, these microorganisms must be suppressed by some means
other than simple mechanical scrubbing. In addition, simple
mechanical scrubbing will not be entirely effective to remove all
stain types and/or whiten the teeth.
[0013] Towards this end, a great deal of research has been aimed at
developing therapeutic compositions and methods of treating the
above conditions, that are effective in suppressing microorganisms.
Also, research has been aimed at developing effective whitening
compositions. Some of this research has focused on oral care
compositions and methods comprising chlorine dioxide or chlorine
dioxide generating compounds. Chlorine dioxide is a very strong
oxidant and is known as a broad spectrum antimicrobial agent.
[0014] The prior art discloses compositions and methods that use
chlorine dioxide for the treatment of various oral care conditions.
Most of these prior art references teach that the delivery of
chlorine dioxide is essential to provide efficacy. This is in
contrast to the present invention which focuses on the delivery of
chlorite ion to the oral cavity, to provide efficacy. The
compositions and methods of the present invention are specifically
and intentionally designed to avoid or minimize the production of
chlorine dioxide in the compositions.
[0015] The prior art teaches a variety of ways to deliver chlorine
dioxide, in oral care compositions, to the oral cavity. For
example, U.S. Pat. Nos. 4,689,215 issued Aug. 25, 1987; 4,837,009
issued Jun. 6, 1989; 4,696,811, issued Sep. 29, 1987; 4,808,389
issued Feb. 28, 1989; 4,786,492 issued Nov. 22, 1988; 4,788,053
issued Nov. 29, 1988; 4,792,442 issued Dec. 20, 1988; 4,818,519
issued Apr. 4, 1989; 4,851,21 issued Jul. 25, 1989; 4,855,135
issued Aug. 8, 1989; 4,793,989 issued Dec. 27, 1988; 4,886,657
issued Dec. 12, 1989; 4,889,714 issued Dec. 26, 1989; 4,925,656
issued May 15, 1990; 4,975,285 issued Dec. 4, 1990; 4,978,535
issued Dec. 18, 1990; 5,200,171 issued Apr. 6, 1993; 5,348,734
issued Sep. 20, 1994; 5,618,550 issued Apr. 8, 1997, and 5,489,435
issued Feb. 6, 1996, all to Perry A. Ratcliffe, teach oral care
compositions and methods of treatment using stabilized chlorine
dioxide.
[0016] Additional prior art references, which teach the generation
and delivery of chlorine dioxide with activator compounds such as
protic acids, reducing sugar activators, etc., include: U.S. Pat.
Nos. 5,281,412, Lukacovic et al., issued Jan. 25, 1994, The Procter
& Gamble Co.; 5,110,652, Kross et al., issued Mar. 31, 1992,
Alcide Corporation; 5,019,402, Kross et al., issued May 28, 1991,
Alcide; 4,986,990, Davidson et al., issued Jan. 22, 1991, Alcide;
4,891,216, Kross et al., issued Jan. 2, 1990, Alcide; 4,330,531,
Alliger, issued May 18, 1982; DE 2,329,753, published Dec. 13,
1973, National Patent Development Corp.; EP 287,074, Kross et al.,
published Oct. 19, 1988, Alcide; EP 565,134, Kross et al.,
published Oct. 13, 1993, Alcide; and WO/95/27472, Richter,
published Oct. 19, 1995.
[0017] Additional prior art references relating to chlorine dioxide
compositions include: GB 2,289,841, Mehmet, published Jun. 12,
1995, Janina International; GB 2,290,233, Drayson et al., published
Dec. 20, 1995, Medical Express Limited; WO 96/25916, Van Den Bosch
et al., published Aug. 29, 1996, Diamond White; JP 054,311,
Tsuchikura, published Mar. 28, 1985; JP 105,610, Tsuchikura,
published Jun. 11, 1985; and WO/89/03179, Partlow et al., published
Apr. 20, 1989, New Generation Products. All of the above references
are incorporated herein by reference in their entirety.
[0018] The above prior art references have not recognized that the
delivery of chlorite ion, itself, to the oral cavity will provide
efficacy in various oral care conditions. Because prior art
references have focused on the delivery of chlorine dioxide for
efficacy, prior art compositions and methods of treatment may have
various drawbacks. For example, compositions comprising chlorine
dioxide can exhibit aesthetic disadvantages such as "chlorine"
(e.g. swimming pool) taste and smell. In addition due to the strong
oxidizing capability of chlorine dioxide, compositions comprising
chlorine dioxide may have certain stability disadvantages,
especially in oral care formulations.
[0019] Therefore, prior art compositions, mentioned above, have not
been entirely satisfactory for the treatment and/or prevention of
gingivitis, plaque, periodontal disease, and/or breath malodor or
for the whitening of teeth. Therefore, additional efficacious
compositions and methods of treatment for these purposes are
desirable.
[0020] As mentioned above, the present invention relates to the
delivery of chlorite ion to the oral cavity for efficacy. The
present invention is specifically designed to avoid or minimize the
production of chlorine dioxide or chlorous acid in the
compositions. The present invention, therefore, relates to oral
care compositions comprising chlorite ion wherein no (or only very
low levels of) chlorine dioxide or chlorous acid is generated or is
present in the oral care compositions at the time of use. Moreover,
the present invention preferably relates to oral care compositions
comprising chlorite ion with relatively alkaline pHs, e.g. at pHs
above 7, whereby no (or only very low levels of) chlorine dioxide
or chlorous acid is generated or is present in the oral care
composition at the time of use. Further, compositions of the
present invention comprise at least a minimum amount of chlorite
ion for effectiveness. These compositions and methods (of the
present invention) are effective even though no (or only very low
levels of) chlorine dioxide or chlorous acid is generated or is
present in these compositions.
[0021] It is the purpose of the present invention to provide
compositions and methods for treating or preventing diseases of the
oral cavity, such as plaque, gingivitis, periodontal disease, and
for treating or preventing other conditions such as breath malodor,
in humans or other animals, by utilizing an effective amount of
chlorite ion wherein no (or only very low levels of) chlorine
dioxide or chlorous acid is generated or is present in the oral
care composition at the time of use. The pH of the final
composition is preferably alkaline, e.g. above pH 7.
[0022] It is also the purpose of the present invention to provide
compositions and methods to whiten teeth, in humans or other
animals, by utilizing an effective amount of chlorite ion wherein
no (or only very low levels of) chlorine dioxide or chlorous acid
is generated or is present in the oral care composition at the time
of use. The pH of the final composition is preferably alkaline,
e.g. above pH 7.
[0023] Further, the present invention relates to oral care
compositions, including therapeutic rinses, especially mouth
rinses, as well as toothpastes, tooth gels, tooth powders,
non-abrasive gels, chewing gums, mouth sprays, and lozenges
(including breath mints). These compositions comprise a minimally
effective amount of chlorite ion.
[0024] These compositions are effective in killing, and/or altering
the bacterial metabolism, and/or for a period of time suppressing
the growth of, microorganisms which cause topically-treatable
infections and diseases of the oral cavity, such as plaque,
gingivitis, periodontal disease, and breath malodor. These
compositions are also effective to whiten teeth.
SUMMARY OF THE INVENTION
[0025] The present invention relates to oral care compositions,
including therapeutic rinses, especially mouth rinses, as well as
toothpastes, tooth gels, tooth powders, non-abrasive gels, chewing
gums, mouth sprays, and lozenges (including breath mints),
comprising:
[0026] (a) a safe and effective amount, preferably a minimally
effective amount, of chlorite ion; and
[0027] (b) a pharmaceutically-acceptable topical, oral carrier;
wherein the level of chlorine dioxide or chlorous acid in the final
composition is less than about 50 ppm; and preferably the pH of the
final composition is greater than 7. More preferably the pH of the
composition is greater than 7.6, even more preferably greater than
8.
[0028] This invention further relates to a method for treating or
preventing diseases of the oral cavity, such as gingivitis, plaque,
periodontal disease, and/or breath malodor, and/or for the
whitening of teeth, in humans or other animals, by applying the
above compositions to the oral cavity and/or teeth.
DETAILED DESCRIPTION OF THE INVENTION
[0029] The present invention relates to compositions and methods of
treating or preventing diseases of the oral cavity (e.g. plaque,
gingivitis, periodontal disease), breath malodor, and for whitening
teeth, in humans or other animals, by topically applying to the
oral cavity, a safe and effective amount of chlorite ion.
[0030] By "diseases or conditions of the oral cavity," as used
herein, is meant diseases of the oral cavity including periodontal
disease, gingivitis, periodontitis, periodontosis, adult and
juvenile periodontitis, and other inflammatory conditions of the
tissues within the oral cavity, plus caries, necrotizing ulcerative
gingivitis, and other conditions such as oral or breath malodor.
Also specifically included are dentoalveolar infections, dental
abscesses (e.g., cellulitis of the jaw; osteomyelitis of the jaw),
acute necrotizing ulcerative gingivitis (i.e., Vincent's
infection), infectious stomatitis (i.e., acute inflammation of the
buccal mucosa), and Noma (i.e., gangrenous stomatitis or cancrum
oris). Oral and dental infections are more fully disclosed in
Finegold, Anaerobic Bacteria in Human Diseases, chapter 4, pp
78-104, and chapter 6, pp 115-154 (Academic Press, Inc., NY, 1977),
the disclosures of which are incorporated herein by reference in
their entirety. The compositions and methods of treatment of the
present invention are particularly effective for treating or
preventing periodontal disease (gingivitis and/or periodontitis)
and breath malodor.
[0031] By "safe and effective amount" as used herein is meant an
amount of a chlorite ion, high enough to significantly (positively)
modify the condition to be treated or to effect the desired
whitening result, but low enough to avoid serious side effects (at
a reasonable benefit/risk ratio), within the scope of sound
medical/dental judgment. The safe and effective amount of a
chlorite ion, will vary with the particular condition (e.g., to
effect whitening, to treat disease of the oral cavity or malodor)
being treated, the age and physical condition of the patient being
treated, the severity of the condition, the duration of treatment,
the nature of concurrent therapy, the specific form (i.e., salt) of
the chlorite source employed, and the particular vehicle from which
the chlorite ion is applied.
[0032] By "toothpaste" as used herein is meant paste, powder, and
tooth gel formulations unless otherwise specified.
[0033] By "oral care composition" or "oral composition" as used
herein is meant a product which is not intentionally swallowed for
purposes of systemic administration of therapeutic agents, but is
retained in the oral cavity for a sufficient time to contact
substantially all of the dental surfaces and/or oral mucosal
tissues for purposes of oral activity.
[0034] By "essentially free of chlorous acid or chlorine dioxide"
as used herein is meant a composition which comprises very low
levels, e.g. less than about 5 ppm, preferably less than about 1
ppm of chlorine dioxide or chlorous acid, using known analytical
methods for measuring chlorine dioxide or chlorous acid as
disclosed hereinafter.
Chlorite Ion Source
[0035] The present invention includes chlorite ion as an essential
ingredient in the compositions and methods of the present
invention. The chlorite ion can come from any type of chlorite
salt. Examples include alkali metal chlorites, alkaline earth metal
chlorites, and any other transition metals, inner transition metal
chlorites and/or polymeric salts. Water soluble chlorite salts are
preferred. Examples of suitable metal chlorites include calcium
chlorite, barium chlorite, magnesium chlorite, lithium chlorite,
sodium chlorite and potassium chlorite. Sodium chlorite and
potassium chlorite are preferred. Sodium chlorite is particularly
preferred. Mixtures of two or more sources of chlorite may also be
used.
[0036] While not intending to be bound by theory, the present
inventors believe that chlorite ion provides antimicrobial
activity, especially selectivity for gram negative anaerobes, for
oral care compositions.
[0037] For dentifrice compositions of the present invention, the
level of chlorite ion is greater than about 0.02%, preferably
greater than about 0.4%, more preferably greater than about 0.56%,
even more preferably greater than about 0.75%, and even more
preferably greater than about 1%, by weight of the composition. The
composition preferably comprises about 2% by weight of the
composition, of chlorite ion.
[0038] For mouthrinse compositions of the present invention, the
level of chlorite ion is greater than about 0.04%, preferably
greater than about 0.075%, more preferably greater than about
0.15%, by weight of the composition.
[0039] For lozenge or breath mint compositions of the present
invention, the amount of chlorite ion is from about 0.1 mg to about
12 mg, preferably from about 1 mg to about 6 mg, per unit.
[0040] For gum compositions of the present invention, the amount of
chlorite ion is from about 0.1 mg to about 12 mg, preferably from
about 1 mg to about 6 mg, per unit.
[0041] For methods of treating or preventing gingivitis or for
whitening the teeth, preferably the compositions comprise from
about 0.75% to about 6%, of chlorite ion, by weight of the
composition.
[0042] In the context of breath odor elimination or reduction, the
compositions and methods of the present invention provide
long-lasting breath protection, e.g. greater than about 3
hours.
[0043] For methods of treating or preventing oral malodor, and for
breath protection lasting greater than about 3 hours, preferably
the compositions comprise from about 0.04% to about 6%, of chlorite
ion, by weight of the composition.
[0044] Chlorite salts are available from various suppliers as
sodium chlorite. Sodium chlorite is commercially available as a
technical grade powder or flake, and as an aqueous liquid
concentrate in a range of concentrations. Example of sources of
sodium chlorite include: sodium chlorite available from Aragonesas
and from Vulcan. These sources generally have no more than 4%
sodium chlorate as well. Preferably the ratio of chlorite to
chlorate is greater than 8:1 and generally about 20:1.
[0045] Preferably, the source of chlorite ion has high purity, e.g.
70% or greater. Furthermore, preferably the compositions of the
present invention are essentially free of hypochlorite metal salt
or hypochlorite ion, dichloroisocyanurate, or salts thereof.
[0046] Preferably, the level of chlorite ion is measured by
gradient separation of inorganic and organic acid anions using Ion
Pac ASII exchange column, available from Dionex Corporation,
Sunnyvale, Calif.
[0047] The final compositions of the present invention preferably
comprise low levels of chlorine dioxide or chlorous acid, or are
essentially free of chlorine dioxide or chlorous acid (have less
than about 5 ppm, preferably less than about 1 ppm of chlorine
dioxide or chlorous acid).
[0048] For mouthwash and dentifrice compositions the level of
chlorine dioxide or chlorous acid in the final composition is
preferably less than about 50 ppm, more preferably less than about
25 ppm, and even more preferably less than about 10 ppm.
[0049] For dual phase compositions the level of chlorine dioxide or
chlorous acid is measured within about 2 to 3 minutes after the two
phases are mixed together.
[0050] Analytical methods to measure the levels of chlorine dioxide
or chlorous acid in the compositions of the present invention are
known in the art. For example, L. S. Clesceri, A. E. Greenberg, and
R. R. Trussel, Standard Methods for the Examination of Water and
Wastewater, 17th ed., American Public Health Association,
Washington, D.C., 1989, pp. 4-75 through 4-83; E. M. Aieta, P. V.
Roberts, and M. Hernandez, J. Am. Water Works Assoc. 76(1), pp.
64-70 (1984); J. D. Pfaff and C. A. Brockhoff, J. Am. Water Works
Assoc. 82(4), pp. 192-195 (1990); G. Gordon, W. J. Cooper, R. G.
Rice, and G. E. Pacey, J. Am. Water Works Assoc. 80(9), pp. 94-108
(1988); D. L. Harp, R. L. Klein, and D. J. Schoonover, J. Am. Water
Works Assoc. 73(7), pp. 387-389 (1981); G. Gordon, W. J. Cooper, R.
G. Rice, and G. E. Pacey, Am. Water Works Assoc. Res. Foundation,
Denver, Colo., 1987, pp. 815. All of these references are herein
incorporated by reference in their entirety.
[0051] The pH of the final composition (either a single phase or
dual phase composition) of the present invention is greater than 7,
preferably greater than 7.6, more preferably greater than 8.
Preferably the pH of the final composition is from 8 to 12, more
preferably the pH is 10.
[0052] Preferably for mouthwash compositions the pH of the final
composition is greater than 7.5, preferably greater than 8.
Preferably the pH of the final composition is from 8 to 12, more
preferably the pH is 10.
[0053] Preferably for dentifrice compositions the pH of the final
composition is greater than 7.6, preferably greater than 8, more
preferably greater than 9. Preferably the pH of the final
composition is from 8 to 12, more preferably the pH is 10.
[0054] For dual phase compositions the pH is measured after the two
phases are mixed together, and is not based on the pH of a single
phase prior to mixing.
[0055] The pH of the final dentifrice composition is measured from
a 3:1 aqueous slurry of toothpaste, e.g. 3 parts water to 1 part
toothpaste.
Pharmaceutically-Acceptable Excipients
[0056] By "pharmaceutically-acceptable excipient" or
"pharmaceutically-acceptable oral carrier," as used herein, is
meant one or more compatible solid or liquid filler diluents or
encapsulating substances which are suitable for topical, oral
administration. By "compatible," as used herein, is meant that the
components of the composition are capable of being commingled
without interaction in a manner which would substantially reduce
the composition's stability and/or efficacy for treating or
preventing breath malodor, plaque, gingivitis, periodontal disease
and to whiten the teeth, according to the compositions and methods
of the present invention.
[0057] The carriers or excipients of the present invention can
include the usual and conventional components of toothpastes
(including gels and gels for subgingival application), mouth
rinses, mouth sprays, chewing gums, and lozenges (including breath
mints) as more fully described hereinafter.
[0058] The compositions of the present invention can be dual phase
compositions or single phase compositions. The chlorite ion,
however, is relatively reactive and will react with certain
carriers or excipients generally used in oral care compositions.
Therefore, based on this reactivity, the preferred compositions of
the present invention are dual phase compositions. These
compositions comprise a first phase and a second phase:
[0059] (a) the first phase comprising chlorite ion; and
[0060] (b) the second phase comprising a
pharmaceutically-acceptable topical, oral carrier and comprising no
chlorite.
[0061] These dual phase compositions comprise two phases, wherein
chlorite ion is placed in a first phase which is to be kept
separate from the second phase. The first phase comprising chlorite
ion can additionally comprise pharmaceutically-acceptable topical,
oral carriers which are compatible with chlorite ion. Preferably
the first phase, in addition to chlorite, comprises one (or more)
compatible binder, humectant, buffer and/or preservative.
Preferably, the second phase, which comprises no chlorite,
comprises flavorant, surfactant, fluoride ion, and/or abrasive.
[0062] Normally, each phase in these two phase compositions, is in
a separate container or in a single container with two chambers.
Prior to use of dual phase composition by the consumer, the two
phases are combined by coextrusion of the two separate phases,
preferably at a 1:1 volume to volume ratio, and the composition is
preferably used immediately after preparation, i.e. within about 5
minutes.
[0063] The two phases, however, can be combined from about 1 minute
to about 1 hour before use, or during the use of the
composition.
[0064] Dual phase containers are disclosed in U.S. Pat. Nos.
5,052,590, Ratcliffe, issued Oct. 1, 1991 and 4,330,531, Alliger,
issued May 18, 1982.
[0065] In another preferred embodiment, chlorite is substantially
anhydrous until just prior to use. For example, preparing a mouth
rinse solution just prior to use by dissolving in water, a
substantially anhydrous concentrate of chlorite, to the necessary
concentration for use in the method of treatments of the present
invention.
[0066] The choice of a carrier to be used is basically determined
by the way the composition is to be introduced into the oral
cavity. If a toothpaste (including tooth gels, etc.) is to be used,
then a "toothpaste carrier" is chosen as disclosed in, e.g., U.S.
Pat. No. 3,988,433, to Benedict, the disclosure of which is
incorporated herein by reference (e.g., abrasive materials, sudsing
agents, binders, humectants, flavoring and sweetening agents,
etc.). If a mouth rinse is to be used, then a "mouth rinse carrier"
is chosen, as disclosed in, e.g., U.S. Pat. No. 3,988,433 to
Benedict (e.g., water, flavoring and sweetening agents, etc.).
Similarly, if a mouth spray is to be used, then a "mouth spray
carrier" is chosen or if a lozenge is to be used, then a "lozenge
carrier" is chosen (e.g., a candy base), candy bases being
disclosed in, e.g., U.S. Pat. No. 4,083,955, to Grabenstetter et
al., which is incorporated herein by reference; if a chewing gum is
to be used, then a "chewing gum carrier" is chosen, as disclosed
in, e.g., U.S. Pat. No. 4,083,955, to Grabenstetter et al., which
is incorporated herein by reference (e.g., gum base, flavoring and
sweetening agents). If a sachet is to be used, then a "sachet
carrier" is chosen (e.g., sachet bag, flavoring and sweetening
agents). If a subgingival gel is to be used (for delivery of
actives into the periodontal pockets or around the periodontal
pockets), then a "subgingival gel carrier" is chosen as disclosed
in, e.g. U.S. Pat. Nos. 5,198,220, Damani, issued Mar. 30, 1993,
P&G, 5,242,910, Damani, issued Sept. 7, 1993, P&G, all of
which are incorporated herein by reference. Carriers suitable for
the preparation of compositions of the present invention are well
known in the art. Their selection will depend on secondary
considerations like taste, cost, and shelf stability, etc.
[0067] Preferred compositions of the subject invention are in the
form of dentifrices, such as toothpastes, tooth gels and tooth
powders. Components of such toothpaste and tooth gels generally
include one or more of a dental abrasive (from about 10% to about
50%), a surfactant (from about 0.5% to about 10%), a thickening
agent (from about 0.1% to about 5%), a humectant (from about 10% to
about 55%), a flavoring agent (from about 0.04% to about 2%), a
sweetening agent (from about 0.1% to about 3%), a coloring agent
(from about 0.01% to about 0.5%) and water (from about 2% to about
45%). Such toothpaste or tooth gel may also include one or more of
an anticaries agent (from about 0.05% to about 0.3% as fluoride
ion), and an anticalculus agent (from about 0.1% to about 13%).
Tooth powders, of course, contain substantially all non-liquid
components.
[0068] Other preferred compositions of the present invention are
non-abrasive gels, including subgingival gels, which generally
include a thickening agent (from about 0.1% to about 20%), a
humectant (from about 10% to about 55%), a flavoring agent (from
about 0.04% to about 2%), a sweetening agent (from about 0.1% to
about 3%), a coloring agent (from about 0.01% to about 0.5%), water
(from about 2% to about 45%), and may comprise an anticaries agent
(from about 0.05% to about 0.3% as fluoride ion), and an
anticalculus agent (from about 0.1% to about 13%).
[0069] Other preferred compositions of the subject invention are
mouthwashes, including mouth sprays. Components of such mouthwashes
and mouth sprays typically include one or more of water (from about
45% to about 95%), ethanol (from about 0% to about 25%), a
humectant (from about 0% to about 50%), a surfactant (from about
0.01% to about 7%), a flavoring agent (from about 0.04% to about
2%), a sweetening agent (from about 0.1% to about 3%), and a
coloring agent (from about 0.001% to about 0.5%). Such mouthwashes
and mouth sprays may also include one or more of an anticaries
agent (from about 0.05% to about 0.3% as fluoride ion), and an
anticalculus agent (from about 0.1% to about 3%).
[0070] Other preferred compositions of the subject invention are
dental solutions. Components of such dental solutions generally
include one or more of water (from about 90% to about 99%),
preservative (from about 0.01% to about 0.5%), thickening agent
(from 0% to about 5%), flavoring agent (from about 0.04% to about
2%), sweetening agent (from about 0.1% to about 3%), and surfactant
(from 0% to about 5%).
[0071] Chewing gum compositions typically include one or more of a
gum base (from about 50% to about 99%), a flavoring agent (from
about 0.4% to about 2%) and a sweetening agent (from about 0.01% to
about 20%).
[0072] The term "lozenge" as used herein includes: breath mints,
troches, pastilles, microcapsules, and fast-dissolving solid forms
including freeze dried forms (cakes, wafers, thin films, tablets)
and fast-dissolving solid forms including compressed tablets. The
term "fast-dissolving solid form" as used herein means that the
solid dosage form dissolves in less than about 60 seconds,
preferably less than about 15 seconds, more preferably less than
about 5 seconds, after placing the solid dosage form in the oral
cavity. Fast-dissolving solid forms are disclosed in copending U.S.
patent application Ser. No. 08/253,890, filed Jun. 3, 1994,
Brideau; U.S. Pat. 4,642,903; U.S. Pat. No. 4,946,684; U.S. Pat.
No. 4,305,502; U.S. Pat. No. 4,371,516; U.S. Pat. No. 5,188,825;
U.S. Pat. No. 5,215,756; U.S. Pat. No. 5,298,261; U.S. Pat. No.
3,882, 228; U.S. Pat. No. 4,687,662; U.S. Pat. No. 4,642,903. All
of these patents are incorporated herein by reference in their
entirety.
[0073] Lozenges include discoid-shaped solids comprising a
therapeutic agent in a flavored base. The base may be a hard sugar
candy, glycerinated gelatin or combination of sugar with sufficient
mucilage to give it form. These dosage forms are generally
described in Remington: The Science and Practice of Pharmacy, 19th
Ed., Vol. II, Chapter 92, 1995. Lozenge compositions (compressed
tablet type) typically include one or more fillers (compressible
sugar), flavoring agents, and lubricants. Microcapsules of the type
contemplated herein are disclosed in U.S. Pat. No. 5,370,864,
Peterson et al., issued Dec. 6, 1994, which is herein incorporated
by reference in its entirety.
[0074] The compositions of the present invention are preferably
essentially free of organic solvents. The compositions of the
present invention are also preferably essentially free of peroxy
compounds.
[0075] Types of carriers or oral care excipients which may be
included in compositions of the present invention, along with
specific non-limiting examples, are:
[0076] Abrasives
[0077] Dental abrasives useful in the topical, oral carriers of the
compositions of the subject invention include many different
materials. The material selected must be one which is compatible
within the composition of interest and does not excessively abrade
dentin. Suitable abrasives include, for example, silicas including
gels and precipitates, insoluble sodium polymetaphosphate, hydrated
alumina, calcium carbonate, dicalcium orthophosphate dihydrate,
calcium pyrophosphate, tricalcium phosphate, calcium
polymetaphosphate, and resinous abrasive materials such as
particulate condensation products of urea and formaldehyde.
[0078] Another class of abrasives for use in the present
compositions is the particulate thermo-setting polymerized resins
as described in U.S. Pat. No. 3,070,510 issued to Cooley &
Grabenstetter on Dec. 25, 1962. Suitable resins include, for
example, melamines, phenolics, ureas, melamine-ureas,
melamine-formaldehydes, urea-formaldehyde,
melamine-urea-formaldehydes, cross-linked epoxides, and
cross-linked polyesters. Mixtures of abrasives may also be
used.
[0079] Silica dental abrasives of various types are preferred
because of their unique benefits of exceptional dental cleaning and
polishing performance without unduly abrading tooth enamel or
dentine. The silica abrasive polishing materials herein, as well as
other abrasives, generally have an average particle size ranging
between about 0.1 to about 30 microns, and preferably from about 5
to about 15 microns. The abrasive can be precipitated silica or
silica gels such as the silica xerogels described in Pader et al.,
U.S. Pat. No. 3,538,230, issued Mar. 2, 1970, and DiGiulio, U.S.
Pat. No. 3,862,307, issued Jan. 21, 1975, both incorporated herein
by reference. Preferred are the silica xerogels marketed under the
trade name "Syloid" by the W.R. Grace & Company, Davison
Chemical Division. Also preferred are the precipitated silica
materials such as those marketed by the J. M. Huber Corporation
under the trade name, Zeodent.RTM., particularly the silica
carrying the designation Zeodent 119.RTM.. The types of silica
dental abrasives useful in the toothpastes of the present invention
are described in more detail in Wason, U.S. Pat. No. 4,340,583,
issued Jul. 29, 1982. The abrasive in the toothpaste compositions
described herein is generally present at a level of from about 6%
to about 70% by weight of the composition. Preferably, toothpastes
contain from about 10% to about 50% of abrasive, by weight of the
composition.
[0080] A particularly preferred precipitated silica is the silica
disclosed in U.S. Pat. Nos. 5,603,920, issued on Feb. 18, 1997;
5,589,160, issued Dec. 31, 1996; 5,658,553, issued Aug. 19, 1997;
5,651,958, issued July 29, 1997, all of which are assigned to the
Procter & Gamble Co. All of these patents are incorporated
herein by reference in their entirety.
[0081] Mixtures of abrasives can be used. All of the above patents
regarding dental abrasives are incorporated herein by reference.
The total amount of abrasive in dentifrice compositions of the
subject invention preferably range from about 6% to about 70% by
weight; toothpastes preferably contain from about 10% to about 50%
of abrasives, by weight of the composition. Solution, mouth spray,
mouthwash and non-abrasive gel compositions of the subject
invention typically contain no abrasive.
[0082] Sudsing Agents (Surfactants)
[0083] Suitable sudsing agents are those which are reasonably
stable and form foam throughout a wide pH range. Sudsing agents
include nonionic, anionic, amphoteric, cationic, zwitterionic,
synthetic detergents, and mixtures thereof. Many suitable nonionic
and amphoteric surfactants are disclosed by U.S. Pat. Nos.
3,988,433 to Benedict; U.S. Pat. No. 4,051,234, issued Sep. 27,
1977, and many suitable nonionic surfactants are disclosed by
Agricola et al., U.S. Pat. No. 3,959,458, issued May 25, 1976, both
incorporated herein in their entirety by reference.
[0084] a.) Nonionic and amphoteric surfactants
[0085] Nonionic surfactants which can be used in the compositions
of the present 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 alkyl-aromatic in nature. Examples of suitable
nonionic surfactants include poloxamers (sold under trade name
Pluronic), polyoxyethylene sorbitan esters (sold under trade name
Tweens), fatty alcohol ethoxylates, 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.
[0086] The amphoteric surfactants useful in the present invention
can be broadly described as derivatives of aliphatic secondary and
tertiary amines in which the aliphatic radical can be a straight
chain or branched and wherein one of the aliphatic substituents
contains from about 8 to about 18 carbon atoms and one contains an
anionic water-solubilizing group, e.g., carboxylate, sulfonate,
sulfate, phosphate, or phosphonate. Other suitable amphoteric
surfactants are betaines, specifically cocamidopropyl betaine.
Mixtures of amphoteric surfactants can also be employed.
[0087] The present composition can typically comprise a nonionic,
amphoteric, or combination of nonionic and amphoteric surfactant
each at a level of from about 0.025% to about 5%, preferably from
about 0.05% to about 4%, and most preferably from about 0.1% to
about 3%.
[0088] b.) Anionic surfactants
[0089] Anionic surfactants useful herein include the water-soluble
salts of alkyl sulfates having from 8 to 20 carbon atoms in the
alkyl radical (e.g., sodium alkyl sulfate) and the water-soluble
salts of sulfonated monoglycerides of fatty acids having from 8 to
20 carbon atoms. Sodium lauryl sulfate and sodium coconut
monoglyceride sulfonates are examples of anionic surfactants of
this type. Other suitable anionic surfactants are sarcosinates,
such as sodium lauroyl sarcosinate, taurates, sodium lauryl
sulfoacetate, sodium lauroyl isethionate, sodium laureth
carboxylate, and sodium dodecyl benzenesulfonate. Mixtures of
anionic surfactants can also be employed. The present composition
typically comprises an anionic surfactant at a level of from about
0.025% to about 9%, preferably from about 0.05% to about 7%, and
most preferably from about 0.1% to about 5%.
[0090] Fluoride Ions
[0091] The present invention may also incorporate free fluoride
ions. Preferred free fluoride ions can be provided by sodium
fluoride, stannous fluoride, indium fluoride, and sodium
monofluorophosphate. Sodium fluoride is the most preferred free
fluoride ion. Norris et al., U.S. Pat. No. 2,946,725, issued Jul.
26, 1960, and Widder et al., U.S. Pat. No. 3,678,154 issued Jul.
18, 1972, disclose such salts as well as others. These patents are
incorporated herein by reference in their entirety.
[0092] The present composition may contain from about 50 ppm to
about 3500 ppm, and preferably from about 500 ppm to about 3000 ppm
of free fluoride ions.
[0093] Thickening Agents
[0094] In preparing toothpaste or gels, it is necessary to add some
thickening material to provide a desirable consistency of the
composition, to provide desirable chlorite release characteristics
upon use, to provide shelf stability, and to provide stability of
the composition, etc. Preferred thickening agents are carboxyvinyl
polymers, carrageenan, hydroxyethyl cellulose, laponite and water
soluble salts of cellulose ethers such as sodium
carboxymethylcellulose and sodium carboxymethyl hydroxyethyl
cellulose. Natural gums such as gum karaya, xanthan gum, gum
arabic, and gum tragacanth can also be used. Colloidal magnesium
aluminum silicate or finely divided silica can be used as part of
the thickening agent to further improve texture.
[0095] Some thickening agents, however, except polymeric polyether
compounds, e.g., polyethylene or polypropylene oxide (M.W. 300 to
1,000,000), capped with alkyl or acyl groups containing 1 to about
18 carbon atoms, may react with chlorite. When chlorite is
formulated separately in a dual phase composition, preferred
thickening agents are hydroxyethyl cellulose and water-soluble
salts of cellulose ethers such as sodium carboxymethyl cellulose
and sodium carboxymethyl hydroxyethyl cellulose.
[0096] A preferred class of thickening or gelling agents includes a
class of homopolymers of acrylic acid crosslinked with an alkyl
ether of pentaerythritol or an alkyl ether of sucrose, or
carbomers. Carbomers are commercially available from B.F. Goodrich
as the Carbopol.RTM. series. Particularly preferred carbopols
include Carbopol 934, 940, 941, 956, and mixtures thereof.
[0097] Copolymers of lactide and glycolide monomers, the copolymer
having the molecular weight in the range of from about 1,000 to
about 120,000 (number average), are useful for delivery of actives
into the periodontal pockets or around the periodontal pockets as a
"subgingival gel carrier." These polymers are described in U.S.
Pat. Nos. 5,198,220, Damani, issued Mar. 30, 1993, P&G,
5,242,910, Damani, issued Sep. 7, 1993, P&G, and 4,443,430,
Mattei, issued Apr. 17, 1984, all of which are incorporated herein
by reference.
[0098] Thickening agents in an amount from about 0.1% to about 15%,
preferably from about 2% to about 10%, more preferably from about
4% to about 8%, by weight of the total toothpaste or gel
composition, can be used. Higher concentrations can be used for
chewing gums, lozenges (including breath mints), sachets,
non-abrasive gels and subgingival gels.
[0099] Humectants
[0100] Another optional component of the topical, oral carriers of
the compositions of the subject invention is a humectant. The
humectant serves to keep toothpaste compositions from hardening
upon exposure to air, to give compositions a moist feel to the
mouth, and, for particular humectants, to impart desirable
sweetness of flavor to toothpaste compositions. The humectant, on a
pure humectant basis, generally comprises from about 0% to about
70%, preferably from about 5% to about 25%, by weight of the
compositions herein. Suitable humectants for use in compositions of
the subject invention include edible polyhydric alcohols such as
glycerin, sorbitol, xylitol, butylene glycol, polyethylene glycol,
and propylene glycol, especially sorbitol and glycerin.
[0101] Flavoring and Sweetening Agents
[0102] Flavoring agents can also be added to the compositions.
Suitable flavoring agents include oil of wintergreen, oil of
peppermint, oil of spearmint, clove bud oil, menthol, anethole,
methyl salicylate, eucalyptol, cassia, 1-menthyl acetate, sage,
eugenol, parsley oil, oxanone, alpha-irisone, marjoram, lemon,
orange, propenyl guaethol, cinnamon, vanillin, thymol, linalool,
cinnamaldehyde glycerol acetal known as CGA, and mixtures thereof.
Flavoring agents are generally used in the compositions at levels
of from about 0.001% to about 5%, by weight of the composition.
[0103] Sweetening agents which can be used include sucrose,
glucose, saccharin, dextrose, levulose, lactose, mannitol,
sorbitol, fructose, maltose, xylitol, saccharin salts, thaumatin,
aspartame, D-tryptophan, dihydrochalcones, acesulfame and cyclamate
salts, especially sodium cyclamate and sodium saccharin, and
mixtures thereof. A composition preferably contains from about 0.1%
to about 10% of these agents, preferably from about 0.1% to about
1%, by weight of the composition.
[0104] In addition to flavoring and sweetening agents, coolants,
salivating agents, warming agents, and numbing agents can be used
as optional ingredients in compositions of the present invention.
These agents are present in the compositions at a level of from
about 0.001% to about 10%, preferably from about 0.1% to about 1%,
by weight of the composition.
[0105] The coolant can be any of a wide variety of materials.
Included among such materials are carboxamides, menthol, ketals,
diols, and mixtures thereof. Preferred coolants in the present
compositions are the paramenthan carboxyamide agents such as
N-ethyl-p-menthan-3-carboxamide, known commercially as "WS-3",
N,2,3-trimethyl-2-isopropylbutanamide, known as "WS-23," and
mixtures thereof. Additional preferred coolants are selected from
the group consisting of menthol, 3-1-menthoxypropane-1,2-di- ol
known as TK-10 manufactured by Takasago, menthone glycerol acetal
known as MGA manufactured by Haarmann and Reimer, and menthyl
lactate known as Frescolat.RTM. manufactured by Haarmann and
Reimer. The terms menthol and menthyl as used herein include
dextro- and levorotatory isomers of these compounds and racemic
mixtures thereof. TK-10 is described in U.S. Pat. No. 4,459,425,
Amano et al., issued Jul. 10, 1984. WS-3 and other agents are
described in U.S. Pat. No. 4,136,163, Watson, et al., issued Jan.
23, 1979; the disclosure of both are herein incorporated by
reference in their entirety.
[0106] Preferred salivating agents of the present invention include
Jambu.RTM. manufactured by Takasago. Preferred warming agents
include capsicum and nicotinate esters, such as benzyl nicotinate.
Preferred numbing agents include benzocaine, lidocaine, clove bud
oil, and ethanol.
[0107] Anticalculus Agent
[0108] The present invention also includes an anticalculus agent,
preferably a pyrophosphate ion source which is from a pyrophosphate
salt. The pyrophosphate salts useful in the present compositions
include the dialkali metal pyrophosphate salts, tetraalkali metal
pyrophosphate salts, and mixtures thereof. Disodium dihydrogen
pyrophosphate (Na.sub.2H.sub.2P.sub.2O.sub.7), tetrasodium
pyrophosphate (Na.sub.4P.sub.2O.sub.7), and tetrapotassium
pyrophosphate (K.sub.4P.sub.2O.sub.7) in their unhydrated as well
as hydrated forms are the preferred species. In compositions of the
present invention, the pyrophosphate salt may be present in one of
three ways: predominately dissolved, predominately undissolved, or
a mixture of dissolved and undissolved pyrophosphate.
[0109] Compositions comprising predominately dissolved
pyrophosphate refer to compositions where at least one
pyrophosphate ion source is in an amount sufficient to provide at
least about 1.0% free pyrophosphate ions. The amount of free
pyrophosphate ions may be from about 1% to about 15%, preferably
from about 1.5% to about 10%, and most preferably from about 2% to
about 6%. Free pyrophosphate ions may be present in a variety of
protonated states depending on a the pH of the composition.
[0110] Compositions comprising predominately undissolved
pyrophosphate refer to compositions containing no more than about
20% of the total pyrophosphate salt dissolved in the composition,
preferably less than about 10% of the total pyrophosphate dissolved
in the composition. Tetrasodium pyrophosphate salt is the preferred
pyrophosphate salt in these compositions. Tetrasodium pyrophosphate
may be the anhydrous salt form or the decahydrate form, or any
other species stable in solid form in the dentifrice compositions.
The salt is in its solid particle form, which may be its
crystalline and/or amorphous state, with the particle size of the
salt preferably being small enough to be aesthetically acceptable
and readily soluble during use. The amount of pyrophosphate salt
useful in making these compositions is any tartar control effective
amount, and is generally from about 1.5% to about 15%, preferably
from about 2% to about 10%, and most preferably from about 3% to
about 8%, by weight of the dentifrice composition.
[0111] Compositions may also comprise a mixture of dissolved and
undissolved pyrophosphate salts. Any of the above mentioned
pyrophosphate salts may be used.
[0112] The pyrophosphate salts are described in more detail in Kirk
& Othmer, Encyclopedia of Chemical Technology, Third Edition,
Volume 17, Wiley-Interscience Publishers (1982), incorporated
herein by reference in its entirety, including all references
incorporated into Kirk & Othmer.
[0113] Optional agents to be used in place of or in combination
with the pyrophosphate salt include such known materials as
synthetic anionic polymers, including polyacrylates and copolymers
of maleic anhydride or acid and methyl vinyl ether (e.g., Gantrez),
as described, for example, in U.S. Pat. No. 4,627,977, to Gaffar et
al., the disclosure of which is incorporated herein by reference in
its entirety; as well as, e.g., polyamino propoane sulfonic acid
(AMPS), zinc citrate trihydrate, polyphosphates (e.g.,
tripolyphosphate; hexametaphosphate), diphosphonates (e.g., EHDP;
AHP), polypeptides (such as polyaspartic and polyglutamic acids),
and mixtures thereof.
[0114] Alkali Metal Bicarbonate Salt
[0115] The present invention may also include an alkali metal
bicarbonate salt. Alkali metal bicarbonate salts are soluble in
water and unless stabilized, tend to release carbon dioxide in an
aqueous system. Sodium bicarbonate, also known as baking soda, is
the preferred alkali metal bicarbonate salt. The present
composition may contain from about 0.5% to about 30%, preferably
from about 0.5% to about 15%, and most preferably from about 0.5%
to about 5% of an alkali metal bicarbonate salt.
[0116] Miscellaneous Carriers
[0117] Water employed in the preparation of commercially suitable
oral compositions should preferably be of low ion content and free
of organic impurities. Water generally comprises from about 5% to
about 70%, and preferably from about 20% to about 50%, by weight of
the composition herein. These amounts of water include the free
water which is added plus that which is introduced with other
materials, such as with sorbitol.
[0118] Titanium dioxide may also be added to the present
composition. Titanium dioxide is a white powder which adds opacity
to the compositions. Titanium dioxide generally comprises from
about 0.25% to about 5% by weight of the dentifrice
compositions.
[0119] Antimicrobial antiplaque agents can also by optionally
present in oral compositions. Such agents may include, but are not
limited to, triclosan, 5-chloro-2-(2,4-dichlorophenoxy)-phenol, as
described in The Merck Index, 11th ed. (1989), pp. 1529 (entry no.
9573) in U.S. Pat. No. 3,506,720, and in European Patent
Application No. 0,251,591 of Beecham Group, PLC, published Jan. 7,
1988; chlorhexidine (Merck Index, no. 2090), alexidine (Merck
Index, no. 222; hexetidine (Merck Index, no. 4624); sanguinarine
(Merck Index, no. 8320); benzalkonium chloride (Merck Index, no.
1066); salicylanilide (Merck Index, no. 8299); domiphen bromide
(Merck Index, no. 3411); cetylpyridinium chloride (CPC) (Merck
Index, no. 2024; tetradecylpyridinium chloride (TPC);
N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine;
delmopinol, octapinol, and other piperidino derivatives; nicin
preparations; zinc/stannous ion agents; antibiotics such as
augmentin, amoxicillin, tetracycline, doxycycline, minocycline, and
metronidazole; and analogs and salts of the above antimicrobial
antiplaque agents. If present, the antimicrobial antiplaque agents
generally comprise from about 0.1% to about 5% by weight of the
compositions of the present invention.
[0120] Anti-inflammatory agents may also be present in the oral
compositions of the present invention. Such agents may include, but
are not limited to, non-steroidal anti-inflammatory agents such as
aspirin, ketorolac, flurbiprofen, ibuprofen, naproxen,
indomethacin, aspirin, ketoprofen, piroxicam and meclofenamic acid,
and mixtures thereof. If present, the anti-inflammatory agents
generally comprise from about 0.001% to about 5% by weight of the
compositions of the present invention. Ketorolac is described in
U.S. Pat. No. 5,626,838, issued May 6, 1997. Both of these
references are incorporated herein by reference in their
entirety.
[0121] Other optional agents include synthetic anionic polymeric
polycarboxylates being employed in the form of their free acids or
partially or preferably fully neutralized water soluble alkali
metal (e.g. potassium and preferably sodium) or ammonium salts and
are disclosed in U.S. Pat. No. 4,152,420 to Gaffar, U.S. Pat. No.
3,956,480 to Dichter et al., U.S. Pat. No. 4,138,477 to Gaffar,
U.S. Pat. No. 4,183,914 to Gaffar et al., and U.S. Pat. No.
4,906,456 to Gaffar et al. Preferred are 1:4 to 4:1 copolymers of
maleic anhydride or acid with another polymerizable ethylenically
unsaturated monomer, preferably methyl vinyl ether
(methoxyethylene) having a molecular weight (M.W.) of about 30,000
to about 1,000,000. These copolymers are available for example as
Gantrez (AN 139 (M.W. 500,000), A.N. 119 (M.W. 250,000) and
preferably S-97 Pharmaceutical Grade (M.W. 70,000), of GAF
Corporation.
[0122] The present invention can also optionally comprise selective
H-2 antagonists including compounds disclosed in U.S. Pat. No.
5,294,433, Singer et al., issued Mar. 15, 1994, which is herein
incorporated by reference in its entirety.
[0123] Composition Use
[0124] A safe and effective amount of the compositions of the
present invention and/or chlorite ion may be topically applied to
the mucosal tissue of the oral cavity, to the gingival tissue of
the oral cavity, and/or to the surface of the teeth, for the
treatment or prevention of the above mentioned diseases or
conditions of the oral cavity, in several conventional ways. For
example, the gingival or mucosal tissue may be rinsed with a
solution (e.g., mouth rinse, mouth spray) containing chlorite ion;
or if chlorite ion is included in a dentifrice (e.g., toothpaste,
tooth gel or tooth powder), the gingival/mucosal tissue or teeth is
bathed in the liquid and/or lather generated by brushing the teeth.
Other non-limiting examples include applying a non-abrasive gel or
paste, which contains chlorite ion, directly to the
gingival/mucosal tissue or to the teeth with or without an oral
care appliance described below; chewing gum that contains chlorite;
chewing or sucking on a breath tablet or lozenge which contains
chlorite ion. Preferred methods of applying chlorite ion to the
gingival/mucosal tissue and/or the teeth are via rinsing with a
mouth rinse solution and via brushing with a dentifrice. Other
methods of topically applying chlorite ion to the gingival/mucosal
tissue and the surfaces of the teeth are apparent to those skilled
in the art.
[0125] The concentration of chlorite ion in the composition of the
present invention depends on the type of composition (e.g.,
toothpaste, mouth rinse, lozenge, gum, etc.) used to apply the
chlorite ion to the gingival/mucosal tissue and/or the teeth, due
to differences in efficiency of the compositions contacting the
tissue and teeth, and due also to the amount of the composition
generally used. The concentration may also depend on the disease or
condition being treated.
[0126] It is preferred that the mouth rinse to be taken into the
oral cavity have a concentration of chlorite ion in the range of
from about 0.04% to about 0.4%, with from about 0.075% to about
0.2% more preferred and from about 0.1% to about 0.2%, by weight of
the composition, even more preferred. Preferably mouth rinse
compositions of the present invention deliver 3.75 to 22.5 mg of
chlorite ion to the oral cavity when approximately 15 ml of the
rinse is used.
[0127] Mouth sprays preferably have chlorite ion concentrations
from about 0.15% to about 4%, with from about 0.2% to about 4% more
preferred, with from about 0.75% to about 2%, by weight of the
composition, even more preferred.
[0128] Preferably for dentifrices (including toothpaste and tooth
gels) and non-abrasive gels, the concentration of chlorite ion is
in the range of from about 0.4% to about 4.5%, by weight of the
composition, with from about 0.75% to about 3% preferred, and from
about 1.5% to about 2%, by weight of the composition, even more
preferred.
[0129] Chewing gums and lozenges (including breath mints), are
generally formulated into compositions of individual unit size
preferably containing from about 0.1 mg to about 12 mg, preferably
from about 1 mg to about 6 mg, of chlorite ion, per unit used in
the oral cavity (i.e. per stick of gum, lozenge, breath mint,
etc.).
[0130] For dual phase compositions the above concentrations of
chlorite ion represent the concentration of chlorite ion after the
two phases are mixed together, which is usually just prior to use
by the consumer.
[0131] For the method of treating diseases or conditions of the
oral cavity, including breath malodor (as well as long lasting
breath-protection), of the present invention, a safe and effective
amount of chlorite ion is preferably applied to the
gingival/mucosal tissue and/or the teeth (for example, by rinsing
with a mouthrinse, directly applying a non-abrasive gel with or
without a device, applying a dentifrice or a tooth gel with a
toothbrush, sucking or chewing a lozenge or breathmint, etc.)
preferably for at least about 10 seconds, preferably from about 20
seconds to about 10 minutes, more preferably from about 30 seconds
to about 60 seconds. The method often involves expectoration of
most of the composition following such contact. The frequency of
such contact is preferably from about once per week to about four
times per day, more preferably from about thrice per week to about
three times per day, even more preferably from about once per day
to about twice per day. The period of such treatment typically
ranges from about one day to a lifetime. For particular oral care
diseases or conditions the duration of treatment depends on the
severity of the oral disease or condition being treated, the
particular delivery form utilized and the patient's response to
treatment. If delivery to the periodontal pockets is desirable,
such as with the treatment of periodontal disease, a mouthrinse can
be delivered to the periodontal pocket using a syringe or water
injection device. These devices are known to one skilled in the
art. Devices of this type include "Water Pik" by Teledyne
Corporation. After irrigating, the subject can swish the rinse in
the mouth to also cover the dorsal tongue and other gingival and
mucosal surfaces. In addition a toothpaste, non-abrasive gel,
toothgel, etc. can be brushed onto the tongue surface and other
gingival and mucosal tissues of the oral cavity.
[0132] For the method of whitening teeth of the oral cavity, a safe
and effective amount of chlorite ion is preferably applied, with or
without an oral care device such as a toothbrush, tray containing
the composition, plastic strips (as disclosed hereinafter), etc.,
to the surface of the teeth: for mouthrinses or mouthsprays and for
toothpastes or tooth gels, preferably for at least about 10
seconds, preferably from about 20 seconds to about 10 minutes, more
preferably from about 30 seconds to about 60 seconds and for
non-abrasive gels (applied with an appliance) preferably at least
about 10 minutes to about 12 hours, preferably from about 20
seconds to about 10 minutes. The method often involves
expectoration of most of the composition following such contact,
preferably followed with rinsing, e.g. with water. The frequency of
such contact is preferably from about once per week to about four
times per day, more preferably from about thrice per week to about
three times per day, even more preferably from about once per day
to about twice per day. The period of such treatment typically
ranges from about one day to a lifetime. The subject may repeat the
application as needed to whiten their teeth. The duration of
treatment is preferably from about 3 weeks to about 3 months, but
may be shorter or longer depending on the severity of the tooth
discoloration being treated, the particular delivery form utilized
and the patient's response to treatment.
[0133] In a preferred application, the consumer applies to their
teeth, a thin plastic film pre-coated with the present composition,
and wears it from about 10 minutes to 8 hours as described above.
The consumer uses a new strip for each application of the present
composition. This type of strip appliance is further described in
P&G Copending applications Ser. Nos. 08/870,664; 08/870,330;
08/870,331 and 08/870,665 all filed Jun. 6, 1997, the disclosures
of which are herein incorporated by reference in their
entirety.
[0134] The following non-limiting examples further describe
preferred embodiments within the scope of the present invention.
Many variations of these examples are possible without departing
from the scope of the invention.
[0135] All percentages used herein are by weight of the composition
unless otherwise indicated.
EXAMPLES
[0136] The following examples are made by conventional processes by
mixing the following:
1 Example 1 - Dual Phase Dentifrice Dentifrice Phase Chlorite Phase
Ingredient Wt. % Ingredient Wt. % Water 20.680 Sodium Chlorite
(80%) 7.50 Sorbitol (70% Solution) 18.534 Carbopol 956.sup.2 5.62
Glycerin 9.000 Water 83.14 Sodium Carbonate 1.000 Sodium Carbonate
0.53 Sodium Fluoride 0.486 Sodium Bicarbonate 0.42 Propylene Glycol
8.000 Sodium Hydroxide 2.79 Hydrated Silica 30.00 Xanthan Gum 0.500
Carboxymethyl Cellulose.sup.1 0.400 Sodium alkyl sulfate 8.000
(27.9% Sol'n) Titanium Dioxide Sodium Saccharin 0.700 Flavor 0.600
Methyl Paraben 2.000 Propyl Paraben 0.070 0.030 Chlorite phase pH =
10 Total 100.00 Total 100.00 After phases mixed in a 1:1 vol./vol.
ratio, pH approximately 8.5 to 9. .sup.1Grade 7M8SF from Aqualon.
.sup.2Available from B.F. Goodrich.
[0137]
2 Example 2 - Dual Phase Dentifrice Dentifrice Phase Chlorite Phase
Ingredient Wt. % Ingredient Wt. % Water 22.180 Sodium Chlorite
(80%) 2.50 Sorbitol (70% Solution) 13.534 Carbopol 956.sup.2 3.72
Glycerin 9.000 Water 91.07 Disodium Phosphate 4.500 Sodium
Carbonate 0.53 Sodium Fluoride 0.486 Sodium Bicarbonate 0.42
Propylene Glycol 8.000 Sodium Hydroxide 1.76 Hydrated Silica 30.00
Xanthan Gum 0.500 Carboxymethyl 0.400 Cellulose.sup.1 Sodium alkyl
sulfate 8.000 (27.9% Sol'n) Titanium Dioxide 0.700 Sodium Saccharin
0.600 Flavor 2.000 Methyl Paraben 0.070 Propyl Paraben 0.030
Chlorite phase pH = 10 Total 100.00 Total 100.00 After phases mixed
in a 1:1 vol./vol. Ratio, pH approximately 7.5. .sup.1Grade 7M8SF
from Aqualon. .sup.2Available from B.F. Goodrich.
[0138]
3 Example 3 - Single Phase Dentifrice Ingredient Wt. % Water 62.277
Sodium Chlorite 3.750 Sodium Fluoride 0.243 Hydrated Silica 25.000
Xanthan Gum 0.600 Carbomer 956.sup.1 0.200 Sodium alkyl 4.000
sulfate (27.9% Sol'n) 1.000 Titanium Dioxide 0.130 Sodium Saccharin
1.000 Flavor 1.800 Sodium Hydroxide (50% Sol'n) Total 100.00
.sup.1Available from B.F. Goodrich.
[0139]
4 Example 4 - Dual Phase Mouthwash Mouthwash Phase Chlorite Phase
Ingredient Wt. % Ingredient Wt. % Water 45.00 Sodium Chlorite (80%)
0.25 Glycerin 19.24 Water 98.80 Sodium Bicarbonate 1.00 Sodium
Carbonate 0.53 Poloxamer 407 0.80 Sodium Bicarbonate 0.42
Polysorbate 80 0.20 Sodium Saccharin 0.20 Flavor 0.50 Color 0.06
Alcohol 33.00 pH = 10 Total 100.00 Total 100.00
[0140]
5 Example 5 - Single Phase Mouthwash Ingredient Wt. % Water 98.80
Sodium Chlorite 0.25 Sodium Carbonate 0.53 Sodium Bicarbonate 0.42
Total 100.00
[0141]
6 Example 6 - Chlorite Lozenge Ingredient Na Chlorite 6 mg. Per
lozenge Flavor As desired Magnesium Stearate 7.5 mg. Stearic Acid
75 mg. Compressible Sugar QS 1500 mg.
[0142]
7 Example 7 Dry Powder Mouthrinse for Reconstitution Ingredient
Weight % Spray Dried Ethanol.sup.1 85.38 Sodium Bicarbonate 5.34
Sodium Chlorite (80%) 1.60 Tastemaker Spray Dried Spearmint #214487
6.40 Aspartame 0.43 Acesulfame Potassium 0.85 Total 100.00
.sup.130% load, available from Takasago.
[0143]
8 Example 8 Dry Powder Mouthrinse for Reconstitution Ingredient
Weight % Spray Dried Ethanol.sup.1 75.00 Sodium Bicarbonate 15.72
Sodium Chlorite (80%) 1.60 Tastemaker Spray Dried Spearmint #214487
6.40 Aspartame 0.43 Acesulfame Potassium 0.85 Total 100.00
.sup.130% load, available from Takasago.
[0144] Add dry ingredients, listed above, in any order, and mix
until achieving a homogeneous mixture. Colorants, to provide color
after adding water to the dry mixture, are optional.
[0145] To make finished mouthwash:
[0146] Example 7: Add 1.874 grams of dry powder blend to 15 ml. of
H.sub.2O in a small dose cup with lid. Shake vigorously until
solids dissolve, rinse and expectorate.
[0147] Example 8: Add 1.874 grams of dry powder blend to 15 ml. of
H.sub.2O in small dose cup with lid. Shake vigorously until solids
dissolve, rinse and expectorate.
9 Example 9 Non-Abrasive Gel Ingredient Weight % Sodium Chlorite
(80%) 3.75 Carbopol 956.sup.1 8.00 Sodium Bicarbonate 0.84 Sodium
Hydroxide (50% Solution) 8.00 (approx. sufficient to get pH 10)
Water QS 100% .sup.1Available from B.F. Goodrich.
[0148]
10 Example 10 Non-Abrasive Gel Ingredient Weight % Sodium Chlorite
(80%) 3.18 Carbopol 956.sup.1 3.90 Sodium Bicarbonate 0.84 Sodium
Hydroxide (50% Solution) 3.90 (approx. sufficient to get pH 10)
Water QS 100% .sup.1Available from B.F. Goodrich.
[0149] For Examples 9 and 10, disperse the Carbopol in water.
Thereafter, add the sodium hydroxide and mix. Then add the sodium
bicarbonate and mix. Check the pH and adjust to pH of 10 with
sodium hydroxide, if needed. Finally, add the sodium chlorite and
mix.
* * * * *