U.S. patent application number 10/026207 was filed with the patent office on 2002-10-17 for cyclodextrins in dental products.
Invention is credited to Nelson, Dennis George Anthony, Sheehan, Craig Joseph.
Application Number | 20020150543 10/026207 |
Document ID | / |
Family ID | 21775580 |
Filed Date | 2002-10-17 |
United States Patent
Application |
20020150543 |
Kind Code |
A1 |
Nelson, Dennis George Anthony ;
et al. |
October 17, 2002 |
Cyclodextrins in dental products
Abstract
Oral rinse and dentifrice compositions, comprising a phenolic
selected from the group consisting of menthol, eucalyptol, methyl
salicylate, thymol, triclosan, and mixtures thereof; and a
cyclodextrin selected from the group consisting of hydroxypropyl
.beta.-cyclodextrin, hydroxyethyl .beta.-cyclodextrin,
hydroxypropyl .gamma.-cyclodextrin, hydroxyethyl
.gamma.-cyclodextrin, .alpha.-cyclodextrin, methyl
.beta.-cyclodextrin, and mixtures thereof. These compositions are
useful in retarding the development of plaque, treating gingivitis,
and in treating the presence of micro-organisms in the oral
cavity.
Inventors: |
Nelson, Dennis George Anthony;
(Mountain Lakes, NJ) ; Sheehan, Craig Joseph;
(Hillsborough, NJ) |
Correspondence
Address: |
Pfizer Inc.
Patent Department
201 Tabor Road
Morris Plains
NJ
07950
US
|
Family ID: |
21775580 |
Appl. No.: |
10/026207 |
Filed: |
December 21, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10026207 |
Dec 21, 2001 |
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09772269 |
Jan 29, 2001 |
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09772269 |
Jan 29, 2001 |
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09299213 |
Apr 23, 1999 |
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6245321 |
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09299213 |
Apr 23, 1999 |
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08839012 |
Apr 23, 1997 |
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5945087 |
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60016135 |
Apr 24, 1996 |
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Current U.S.
Class: |
424/49 ; 424/54;
514/58 |
Current CPC
Class: |
A61K 8/347 20130101;
Y10S 514/922 20130101; A61K 8/37 20130101; Y10S 514/944 20130101;
A61K 8/498 20130101; A61Q 11/00 20130101; A61K 8/738 20130101; A61K
8/34 20130101 |
Class at
Publication: |
424/49 ; 424/54;
514/58 |
International
Class: |
A61K 007/16; A61K
007/22; A61K 031/724 |
Claims
1. A stable oral rinse composition, comprising: a) from about 0.01%
to about 2.5% by weight of a phenolic, said phenolic selected from
the group consisting of menthol, eucalyptol, methyl salicylate,
thymol, triclosan, and mixtures thereof; b) from about 0.1% by
weight to about 25% by weight of a cyclodextrin, said soluble
cyclodextrin selected from the group consisting of hydroxypropyl
.beta.-cyclodextrin, hydroxyethyl .beta.-cyclodextrin,
hydroxypropyl .gamma.-cyclodextrin, hydroxyethyl
.gamma.-cyclodextrin, .alpha.-cyclodextrin, methyl
.beta.-cyclodextrin, and mixtures thereof; c) up to about 25% by
weight ethanol; and d) an orally acceptable carrier.
2. A stable oral rinse composition according to claim 1, wherein
the amount of cyclodextrin is from about 1% by weight to about 5%
by weight.
3. A stable oral rinse composition according to claim 1, wherein
the amount of ethanol is up to about 15% by weight.
4. A stable oral rinse composition according to claim 1, further
including up to about 4% by weight of an orally acceptable
surfactant selected from the group consisting of an anionic
surfactant, a nonionic surfactant, or mixtures thereof.
5. A stable oral rinse composition according to claim 4, wherein
the amount of orally acceptable surfactant is up to about 1% by
weight.
6. A stable oral rinse composition according to claim 1, further
including up to about 5% by weight of an orally acceptable
antiplaque agent.
7. A stable oral rinse composition according to claim 6, wherein
the orally acceptable antiplaque agent is selected from the group
consisting of cetyl pyridinium chloride, cetyl pyridinium chloride
related quaternary pharmaceutically acceptable salts,
chlorhexidine, zinc pharmaceutically acceptable salts, stannous
pharmaceutically acceptable salts and pharmaceutically acceptable
peroxygens.
8. A stable oral rinse composition according to claim 1, further
including an orally acceptable anticalculus agent.
9. A stable oral rinse composition according to claim 8, wherein
the orally acceptable anticalculus agent includes up to about 10%
by weight of a pyrophosphate pharmaceutically acceptable salt.
10. A stable oral rinse composition according to claim 1, further
including an orally acceptable suitable fluoride ion source
sufficient to provide from about 50 ppm to about 2500 ppm
fluoride.
11. A stable oral rinse composition according to claim 10, wherein
the amount of the orally acceptable suitable fluoride ion source
provides from about 50 ppm to about 250 ppm fluoride.
12. A dentifrice in the form of a toothpaste or tooth gel,
comprising: a) from about 0.01% to about 10% by weight of a
phenolic, said phenolic selected from the group consisting of
menthol, eucalyptol, methyl salicylate, thymol, triclosan, and
mixtures thereof; b) from about 0.1% by weight to about 60% by
weight of a cyclodextrin, said cyclodextrin selected from the group
consisting of hydroxypropyl .beta.-cyclodextrin, hydroxyethyl
.beta.-cyclodextrin, hydroxypropyl .gamma.-cyclodextrin,
hydroxyethyl .gamma.-cyclodextrin, .alpha.-cyclodextrin and methyl
.beta.-cyclodextrin, and mixtures thereof; c) up to about 60% by
weight of an orally acceptable dental abrasive; and d) an orally
acceptable carrier.
13. A dentifrice according to claim 12, wherein the amount of
cyclodextrin is from about 5% by weight to about 30% by weight.
14. A dentifrice according to claim 12, further including up to
about 4% by weight of an orally acceptable surfactant selected from
the group consisting of an anionic surfactant, a nonionic
surfactant, or mixtures thereof.
15. A dentifrice according to claim 14, wherein the amount of
orally acceptable surfactant is from about 0.5% by weight to about
4% by weight.
16. A dentifrice according to claim 12, further including up to
about 5% by weight of an orally acceptable antiplaque agent.
17. A dentifrice according to claim 16, wherein the orally
acceptable antiplaque agent is selected from the group consisting
of cetyl pyridinium chloride, cetyl pyridinium chloride related
quaternary pharmaceutically acceptable salts, chlorhexidine, zinc
pharmaceutically acceptable salts, stannous pharmaceutically
acceptable salts and pharmaceutically acceptable peroxygens.
18. A dentifrice according to claim 12, further including an orally
acceptable anticalculus agent.
19. A dentifrice according to claim 18, wherein the orally
acceptable anticalculus agent includes up to about 10% by weight of
a pyrophosphate pharmaceutically acceptable salt.
20. A dentifrice according to claim 12, wherein the amount of
orally acceptable dental abrasive is from about 10% by weight to
about 40% by weight.
21. A dentifrice according to claim 12, wherein the orally
acceptable dental abrasive selected from the group consisting of
silica, alumina, calcium pyrophosphate and calcium carbonate.
22. A dentifrice according to claim 12, further including an orally
acceptable suitable fluoride ion source sufficient to provide from
about 50 ppm to about 2500 ppm fluoride.
23. A dentifrice according to claim 22, wherein the amount of the
orally acceptable suitable fluoride ion source sufficient to
provide from about 250 ppm to about 1500 ppm fluoride.
24. A stable oral rinse composition, comprising: a) from about
0.01% to about 0.5% by weight of a phenolic, said phenolic selected
from the group consisting of menthol, eucalyptol, methyl
salicylate, thymol, triclosan, and mixtures thereof; b) from about
0.1% by weight to about 5% by weight of a cyclodextrin, said
soluble cyclodextrin selected from the group consisting of
hydroxypropyl .beta.-cyclodextrin, hydroxyethyl
.beta.-cyclodextrin, hydroxypropyl .gamma.-cyclodextrin,
hydroxyethyl .gamma.-cyclodextrin, .alpha.-cyclodextrin, methyl
.beta.-cyclodextrin, and mixtures thereof; c) up to about 15% by
weight ethanol; and d) up to about 1% by weight of an orally
acceptable surfactant selected from the group consisting of an
anionic surfactant, a nonionic surfactant, or mixtures thereof; and
d) an orally acceptable carrier.
25. A dentifrice in the form of a toothpaste or tooth gel,
comprising: a) from about 0.01% to about 3% by weight of a
phenolic, said phenolic selected from the group consisting of
menthol, eucalyptol, methyl salicylate, thymol, triclosan, and
mixtures thereof; b) from about 0.1% by weight to about 30% by
weight of a cyclodextrin, said cyclodextrin selected from the group
consisting of hydroxypropyl .beta.-cyclodextrin, hydroxyethyl
.beta.-cyclodextrin, hydroxypropyl .gamma.-cyclodextrin,
hydroxyethyl .gamma.-cyclodextrin, .alpha.-cyclodextrin and methyl
.beta.-cyclodextrin, and mixtures thereof; c) up to about 40% by
weight of an orally acceptable dental abrasive; d) up to about 4%
by weight of an orally acceptable surfactant selected from the
group consisting of an anionic surfactant, a nonionic surfactant,
or mixtures thereof; e) an orally acceptable suitable fluoride ion
source sufficient to provide from about 250 ppm to about 1500 ppm
fluoride; and f) an orally acceptable carrier.
26. A method for retarding development of plaque on a dental
surface in the oral cavity of a mammal, comprising administering to
said dental surface an amount of a composition according to claim 1
effective in retarding said development of plaque.
27. A method for retarding development of plaque on a dental
surface in the oral cavity of a mammal, comprising administering to
said dental surface an amount of a dentifrice according to claim 12
effective in retarding said development of plaque.
28. A method of treating gingivitis, comprising administering to a
mammal in need of such treatment an amount of a composition
according to claim 1 effective in treating gingivitis.
29. A method of treating gingivitis, comprising administering to a
mammal in need of such treatment an amount of a dentifrice
according to claim 12 effective in treating gingivitis.
30. A method of treating the presence of micro-organisms in the
oral cavity of a mammal, comprising administering to the mammal in
need of such treatment an amount of a composition according to
claim 1 effective in reducing the viable population of said
micro-organisms.
31. A method of treating the presence of micro-organisms in the
oral cavity of a mammal, comprising administering to the mammal in
need of such treatment an amount of a dentifrice according to claim
12 effective in reducing the viable population of said
micro-organisms.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to dental products comprising
cyclodextrins.
[0002] Dental plaque is present to some degree, in the form of a
film, on virtually all dental surfaces. It is a by-product of
microbial growth, and comprises a dense microbial layer consisting
of a mass of micro-organisms embedded in a polysaccharide matrix.
The micro-organisms present in plaque are mainly coccoidal
organisms, particularly in early plaque. As plaque ages and
matures, gram negative anaerobes and filamentous organisms appear
and become more common after a few days. Plaque itself adheres to
dental surfaces and may not be removed completely even with a
rigorous brushing regimen and can build up, for example, in
recessed areas of tooth surfaces, such as approximal regions and
fissures. Moreover, plaque rapidly reforms on the tooth surface
after it is removed.
[0003] Plaque may form on any part of the tooth surfaces, and can
be found particularly at the gingival margin, in pits and fissures
in the enamel, and on the surface of dental calculus. The danger
associated with the formation of plaque on the teeth lies in the
tendency of plaque to build up and eventually contribute to
gingivitis, periodontitis and other types of periodontal disease,
as well as dental caries and dental calculus.
[0004] More specifically, dental plaque is a precursor to the
formation of the hard crystalline build up on teeth referred to as
dental calculus. Both the bacterial and the nonbacterial components
of plaque mineralize to form calculus, which comprises mineralized
bacteria as well as organic constituents, such as epithelial cells,
live bacteria, salivary proteins, leukocytes, and crystalline
substances containing both calcium and phosphorous, e.g.,
hydroxyapatite, Ca.sub.10(PO.sub.4).sub.6(OH).sub.2, octacalcium
phosphate, Ca.sub.8(HPO.sub.4).sub.2(PO.sub.4).sub.4.5H.sub.2- O,
brushite, CaHPO.sub.4.2H.sub.2O, and whitlockite, which is
considered to have the formula .beta.-Ca.sub.3(PO.sub.4).sub.2.
Dental plaque and, hence, calculus are particularly prone to form
at the gingival margin, i.e., the junction of the tooth and
gingiva. The buildup of plaque at, and below, the gingival margin
is believed to be the prime cause of gingivitis and periodontal
disorders.
[0005] Mouthwashes have been formulated to contain antimicrobial
ingredients whose function is to reduce the buildup of plaque,
either by the direct bactericidal action (i.e. killing) on plaque
and salivary micro-organisms and by bacteriostatic action (i.e.
growth inhibition) on plaque and salivary micro-organisms. Scheie,
A. AA. (1989) Modes of Action of Currently Known Chemical
Anti-Plaque Agents Other than Chlorhexidine. J. Dent. Res. 68
Special Issue: 1609-1616. Oral compositions including mouthwashes
and dentifrices containing phenolic compounds are referred to in
U.S. Pat. Nos. 4,945,087; WO 94/16.16,674; WO 94/07477; and WO
94/18939. Oral composition including triclosan are referred to in
the following: U.S. Pat. Nos. 4,892,220; 5,032,386; 5,037,637;
5,034,154; 5,080,887; 5,236,699; 5,043,154; 5,032,385; and
5,156,835 as well as EPO 85303216.7.
[0006] However phenolics useful in oral compositions have low
aqueous solubilities which limit their use in oral compositions and
they require high levels of either 1) alcohol; 2) surfactants; or
3) co-solvents or combinations of the above for sufficient
solubility in the carrier. PCT Appln No. WO 94/16674.
[0007] For example, thymol has been used as a anthelmintic and
antiseptic, in mouthwashes containing a combination of menthol,
methyl salicylate, eucalyptol and thymol. However, these
compositions are characterized by their relatively high alcohol
levels which causes them to have negative aesthetics, including
excessive "bite" and "burn."
[0008] Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a
phenolic, nonionic antimicrobial agent used in various soap and
toiletry products. In the oral care area, triclosan has been used
as a plaque-inhibitory agent in various toothpastes and
mouthrinses. Triclosan is a broad-spectrum antimicrobial that has
shown activity in in vitro assays. Regos, J. and Hitz, H. R. (1974)
Investigation of Mode of Action of Triclosan, A Broad Spectrum
Antimicrobial Agent. Zbl Bakt Hyg I Abt Orig A 226:390-401;
Vischer, W. A. and Regos, J. (1974) Antimicrobial Spectrum of
Triclosan, A Broad-Spectrum Antimicrobial Agent for Topical
Application. Zbl Bakt Hyg I Agt Orig A 226:376-389, including
chemostat studies; Bradshaw, D. J., Marsh, P. D., Watson, G. K. and
Cummins, D. (1993) The Effects of Triclosan and Zinc Citrate, Alone
and in Combination, on a Community of Oral Bacteria Grown in vitro.
J. Dent Res. 72:25-30; Herles, S., Olsen, S., Afflito, J. and
Gaffar, A. (1994) Chemostat Flow Cell System: An in vitro Model for
the Evaluation of Antiplaque Agents. J. Dent Res. 73:1748-1755, as
well as animal tests; Nabi, N., Mukerjee, C., Schmid, R., Gaffar,
A. (1989) In Vitro and In Vivo Studies on Triclosan/PVM/MA
copolymer/NaF Combination as an Antiplaque Agent. Am. J. Dent. Spec
Issue No. 2: 197-206; and human clinical studies; Garcia-Godoy, F.,
Garcia-Godoy, F., DeVizio, W., Volpe, A. R., Ferlauto, R. J. and
Miller, J. M. (1990) Effect of a Triclosan/Copolymer/Fluoride
Dentifrice on Plaque Formation and Gingivitis: A 7-month Clinical
Study. Am. J. Dent. 3:S15-S26; Rustogi, K. N., Petrone, D. M.,
Singh, S. M., Volpe, A. R. and Tavss, E. (1990) Clinical Study of a
Pre-brush and Triclosan/Copolymer Mouthrinse: Effect on Plaque
Formation. Am. J. Dent. 3:S67-S69; and Saxton, C. A., Lane, R. M.
and van der Ouderaa, F. (1987) The Effects of a Dentifrice
Containing a Zinc Salt and a Non-cationic Antimicrobial Agent on
Plaque and Gingivitis. J. Clin. Periodontol. 57:555-561. Although
triclosan when delivered orally, is taken up by plaque and is
moderately substantive, its bioactivity is limited by its poor
aqueous solubility. Thus, triclosan has to be solubilized either by
alcohol or surfactants such as sodium lauryl sulfate when
formulated into a conventional dentifrice or mouthrinse product.
Kjaerheim, V., Waaler, S. M., Rolla, G. (1994) Significance of
Choice of Solvents for the Clinical Effect of Triclosan-containing
Mouthrinses. Scand. J. Dent. Res. 102:202-205.
[0009] Cyclodextrins are known to form inclusion complexes with
various compounds. The cyclodextrin molecule consists of
glucopyranose units arranged in a torus-like or donut-like
configuration having all the secondary hydroxyl groups located on
one side of the torus and all primary hydroxyl groups located on
the other side. Alpha, beta, and gamma cyclodextrin contain 6, 7
& 8 cyclic glucopyranose units, respectively, in the torus
shell. The "lining" of the internal cavity is formed by hydrogen
and glucosidic oxygen-bridge atoms and therefore the surface is
slightly apolar.
SUMMARY OF THE INVENTION
[0010] The present invention relates to an oral rinse composition,
comprising:
[0011] a) from about 0.01% to about 2.5% by weight of a phenolic,
said phenolic selected from the group consisting of menthol,
eucalyptol, methyl salicylate, thymol, triclosan, and mixtures
thereof;
[0012] b) From about 0.1% by weight to about 25% by weight of a
cyclodextrin, said cyclodextrin selected from the group consisting
of hydroxypropyl .beta.-cyclodextrin, hydroxyethyl
.beta.-cyclodextrin, hydroxypropyl .gamma.-cyclodextrin,
hydroxyethyl .gamma.-cyclodextrin, .alpha.-cyclodextrin, methyl
.beta.-cyclodextrin, and mixtures thereof;
[0013] c) Up to about 25% by weight ethanol; and
[0014] d) an orally acceptable carrier.
[0015] The present invention also relates to a dentifrice in the
form of a toothpaste or tooth gel, comprising:
[0016] a) from about 0.01% to about 10% by weight of a phenolic,
said phenolic selected from the group consisting of menthol,
eucalyptol, methyl salicylate, thymol, triclosan, and mixtures
thereof;
[0017] b) From about 0.1% by weight to about 60% by weight of a
cyclodextrin, said cyclodextrin selected from the group consisting
of hydroxypropyl .beta.-cyclodextrin, hydroxyethyl
.beta.-cyclodextrin, hydroxypropyl .gamma.-cyclodextrin,
hydroxyethyl .gamma.-cyclodextrin, .alpha.-cyclodextrin, methyl
.beta.-cyclodextrin, and mixtures thereof;
[0018] c) up to about 60% by weight of an orally acceptable dental
abrasive, for example, silica, alumina, calcium pyrophosphate and
calcium carbonate; and
[0019] d) an orally acceptable carrier.
[0020] The present also relates to a method for retarding
development of plaque on a dental surface in the oral cavity of a
mammal, comprising administering to said dental surface an amount
of said oral rinse composition effective in retarding said
development of plaque.
[0021] The present also relates to a method for retarding
development of plaque on a dental surface in the oral cavity of a
mammal, comprising administering to said dental surface an amount
of said dentifrice effective in retarding said development of
plaque.
[0022] The present also relates to a method of treating gingivitis,
comprising administering to a mammal in need of such treatment an
amount of said oral rinse composition effective in treating
gingivitis.
[0023] The present also relates to a method of treating gingivitis,
comprising administering to a mammal in need of such treatment an
amount of said dentifrice effective in treating gingivitis.
[0024] The present also relates to a method of treating the
presence of micro-organisms in the oral cavity of a mammal,
comprising administering to the mammal in need of such treatment an
amount of said oral rinse composition effective in reducing the
viable population of said micro-organisms.
[0025] The present also relates to a method of treating the
presence of micro-organisms in the oral cavity of a mammal,
comprising administering to the mammal in need of such treatment an
amount of said dentifrice effective in reducing the viable
population of said micro-organisms.
DETAINED DESCRIPTION OF THE INVENTION
[0026] Compositions of the present invention include low-alcohol
oral care .compositions that contain cyclodextrin compounds which
solubilize phenolic antimicrobial compounds. As a result of higher
levels of solubilized phenolics in a solution, the phenolic
compounds have improved bioavailability in treating plaque, as well
as providing compositions having excellent low-temperature
stability. These compositions retard the development of plaque as
well as treat gingivitis and periodontal diseases without the use
of high alcohol levels, high surfactant levels or the use of other
co-solvents.
[0027] Phenolics useful as antimicrobials in the present invention
and effective in treating micro-organisms present in the oral
cavity of a mammal include menthol, methyl salicylate, eucalyptol,
thymol and triclosan. Thymol and triclosan are generally considered
to have the best antimicrobial activity of these phenolics. For
oral rinses, phenolic compounds or mixtures thereof preferably
range from about 0.01% by weight to about 0.5% by weight, more
preferably from about 0.05% by weight to about 0.3% by weight. For
dentifrices, the amount of phenolic compounds or a mixture thereof
preferably range from about 0.01% by weight to about 5% by weight,
more preferably from about 0.25% by weight to about 3% by
weight.
[0028] Molecules, or functional groups of molecules having
molecular dimensions that match the cyclodextrin cavity, being less
hydrophilic (i.e. more hydrophobic) than water, will position
themselves in the cyclodextrin cavity at the expense of water
molecules. In aqueous solutions, the slightly apolar cyclodextrin
cavity is occupied by water molecules which are energetically
unfavored (polar-apolar interaction) and are therefore readily
substituted by appropriate "guest molecules" which are less polar
than water. In the case of the present invention, the "guest
molecules" are the phenolic ingredients mentioned above.
[0029] Suitable cyclodextrins useful in the present invention
include hydroxypropyl .beta.-cyclodextrin, hydroxyethyl
.beta.-cyclodextrin, hydroxypropyl .gamma.-cyclodextrin,
hydroxyethyl .gamma.-cyclodextrin, .alpha.-cyclodextrin and methyl
.beta.-cyclodextrin. Suitable candidate cyclodextrins typically
have to have an aqueous solubility of at least about 10% by weight
and form sufficiently soluble phenolic-cyclodextrin complexes to be
suitable for this invention. Hydroxypropyl .beta.-cyclodextrin is
the preferred cyclodextrin.
[0030] Each of the seven cyclic glucopyranose units in
.beta.-cyclodextrin contains three hydroxyl groups in the 2-,3- and
6-positions, which can be etherified. In the case of the partially
etherified cyclodextrin derivatives used in this invention, only
some of these positions are substituted with hydroxyethyl or
hydroxypropyl groups. A wide range of substitutions can be made per
molecule up to a maximum of 18. The preferred range of substitution
ranges from about 0.5 to 8 positions. Thus, hydroxypropyl
.beta.-cyclodextrin is a chemically modified cyclodextrin
consisting of an amorphous isomeric mixture of thousands of
geometric and optical isomers with varying degrees of substitution
and varying numbers of hydroxypropyl substituents, however the size
of the cyclodextrin cavity is constant for these isomers.
[0031] For oral rinses, these amount of soluble cyclodextrin ranges
from about 0.1% by weight to about 25% by weight, preferably from
about 0.5% by weight to about 20% by weight, more preferably from
about 1% by weight to about 5% by weight, selected from the group
consisting of hydroxypropyl .beta.-cyclodextrin, hydroxyethyl
.beta.-cyclodextrin, hydroxypropyl .gamma.-cyclodextrin,
hydroxyethyl .gamma.-cyclodextrin, .alpha.-cyclodextrin, methyl
.beta.-cyclodextrin, and mixtures thereof are useful for the
invention. For dentifrices, the amount of soluble cyclodextrin
ranges from about 0.1% by weight to about 60% by weight, preferably
from about 5% by weight to about 30% by weight selected from the
group consisting of hydroxypropyl .beta.-cyclodextrin, hydroxyethyl
.beta.-cyclodextrin, hydroxypropyl .gamma.-cyclodextrin,
hydroxyethyl .gamma.-cyclodextrin, .alpha.-cyclodextrin, methyl
.beta.-cyclodextrin, and mixtures thereof are useful for the
invention.
[0032] For dentifrice compositions suitable abrasives include
precipitated silica or silica gels which have an average particle
size ranging from about 0.1 to about 50 microns. Preferred silica
abrasives include those marketed under the tradename
"Sylodent.RTM." or "Syloid.RTM." by the W. R. Grace & Co. and
those marketed under the tradename "Zeodent.RTM." by the J. M.
Huber Corp. Other suitable abrasives, having a suitable particle
size as described above, include .beta.-phase calcium
pyrophosphate, alumina and calcium carbonate. The amount of
abrasive in a dentifrice composition ranges up to about 60% by
weight, preferably from 10% by weight to 40% by weight.
[0033] Dentifrice and oral rinse compositions also may contain a
suitable fluoride source. Typical sources include soluble salts of
the fluoride ion; e.g. sodium fluoride, potassium fluoride,
stannous fluoride, stannous fluorozirconate etc.; or, soluble salts
of the monofluorophosphate ion; e.g. sodium monofluorophosphate
etc. The preferred fluoride source is sodium fluoride. The fluoride
ion source should be sufficient to provide from about 50 ppm to
about 2,500 ppm fluoride, preferably from about 250 ppm to about
1500 ppm for dentifrices and from about 50 ppm to about 250 ppm
fluoride for oral rinses.
[0034] A liquid carrier generally includes mixtures of water and
ethanol for oral rinses, although the carrier can be alcohol-free,
especially in dentifrices. For oral rinses, the amount of water
ranges upwards from about 25% by weight. The amount of alcohol
ranges by weight from about 0% to about 25% by weight, preferably
from about 0% by weight to about 15% by weight. For dentifrices,
the amount of water ranges from about 0% by weight to about 60% by
weight, preferably from about 0% by weight to about 40% by
weight.
[0035] The pH of the oral rinses and dentifrice compositions can
range from about 3.5 to about 8.5.
[0036] The oral rinse compositions, for example, Examples 1 to 5,
are unusually stable so as to be substantially clear and
substantially free of precipitation, flocculation, or crystal
formation at about room temperature (about 25.degree. C.) as well
as at low temperatures of at least about 5.degree. C. for at least
about 1 week. The low temperature stability of these compositions
is determined by cooling the compositions to about 5.degree. C.,
storing for at least seven days and determining whether any
precipitate, crystallized or flocculated material is formed in the
clear compositions (solutions and gels).
[0037] Oral surfactants useful in the present invention include
nonionic and anionic surfactants. Oral surfactants employed include
block co-polymers of polyoxyethylene and polyoxypropylene such as
the Pluronics from BASF. Other oral surfactants include soluble
alkyl sulfonates having 10 to 18 carbon atoms, such as sodium
lauryl sulfate, and sulfates of monoglycerides of fatty acids
having 10 to 18 carbon atoms or sarcosinates (including salts and
derivatives) such as sodium-N-lauroyl sarcosinate. Mixtures of
anionic and nonionic surfactants can be used. These ingredients are
generally present from about 0% by weight to about 4% by weight,
preferably from about 0% by weight to about 1% by weight for oral
rinses and from about 0.5% by weight to about 4% by weight for
dentifrices.
[0038] Additional antiplaque agents can also be optionally added to
the compositions. These include cetyl pyridinium chloride and
related quaternary salts, chlorhexidine, zinc salts such as zinc
chloride, stannous salts such as stannous chloride or stannous
fluoride and peroxygens such as hydrogen peroxide and carbamide
peroxide. These optional antiplaque agents are generally present at
levels ranging form about 0% to about 5% by weight.
[0039] Additional anticalculus agents can be optionally added to
the compositions. These include tetra-alkali or di-alkali metal
pyrophosphate salts and zinc salts, such as, but not limited to,
zinc chloride etc. These optional anticalculus agents are generally
present at levels ranging from about 0% by weight to about 10% by
weight for pyrophosphate salts and from about 0% by weight to about
3% by weight for zinc salts.
[0040] In compositions relating to the invention, preservatives may
be used, especially for non-alcohol or low alcohol compositions.
These include benzoic acid, sodium benzoate, methylparaben,
propylparaben, sorbic acid and potassium sorbate. These optional
preservative agents are generally present at levels ranging from
about 0% by weight to about 2% by weight.
[0041] In compositions relating to the invention, buffering systems
may be used to stabilize the pH in the product. Typical buffering
systems include, but are not limited to, citrate, benzoate,
gluconate and phosphate. Buffering systems are present in
concentrations from about 0.01% by weight to about 1% by
weight.
[0042] In addition to the above ingredients, the invention may
include other optional ingredients to impart desired mouth feel and
provide flavoring and coloring.
[0043] Humectants are an optional component of the compositions.
For oral rinses they impart a moist and elegant feel to the mouth
and in toothpaste compositions they prevent hardening on exposure
to air. Some humectants can provide sweetness to the composition.
Suitable humectants include edible polyhydric alcohols such as
glycerin, sorbitol, propylene glycol and xylitol. The humectant
generally is present in an amount ranging from 0% by weight to 30%
by weight for oral rinses and 0% by weight to 70% by weight for
dentifrice compositions.
[0044] Thickening agents or binders are an optional component of
the compositions. Typical thickening include, xanthan gum,
carrageenan, carboxyvinyl polymers, carbomers, cellulose gums such
as carboxymethyl cellulose, cellulose derivatives such as
hydroxyethylcellulose and silicas. Thickeners are usually present
in the compositions from about 0% by weight to 2% by weight.
Xanthan gum is the preferred thickener in oral rinses. In
dentifrices, silica-based thickeners can be used at concentrations
from 0% by weight to about 20% by weight. "Sylox.RTM." by W. R.
Grace & Co. is the tradename of the preferred silica-based
thickener.
[0045] Flavoring agents can be added to the compositions. The
flavorant may be a flavoring oil or mixture of flavoring oils such
as oil of peppermint, spearmint, wintergreen, clove, sassafras,
lemon, orange or lime. Sweetening agents such as saccharin,
lactose, maltose, aspartame, sodium cyclamate, polydextrose etc.
can be added to the compositions. Flavoring agents generally are
present in an amount ranging from 0.001% by weight to about 0.5% by
weight for oral rinses and 0.25% by weight to about 5% by weight
for dentifrice compositions. Sweetening agents generally are
present in an amount ranging from 0.001% by weight to about 5% by
weight for oral rinse and dentifrice compositions. Coloring agents
generally are present in an amount ranging from 0% by weight to
0.01% by weight.
EXAMPLE 1
[0046] A dental rinse was formulated by adding Hydroxypropyl
.beta.-cyclodextrin and poloxamer to water using a Master
Servodyne.RTM. mixer with high-lift blade rotating at 200-300 rpm
to give a clear aqueous solution. Benzoic acid, thymol, menthol,
eucalyptol, methyl salicylate and flavor were added with stirring
to give a clear solution. Sodium citrate, citric acid, dye,
sorbitol and sodium saccharin were then added with continual
stirring to give a clear solution. The resulting clear blue-green
product was mixed for a further 30 minutes. The product had a pH of
approximately 4.0.
1 Ingredient Weight Percent poloxamer 407 0.50 sodium citrate 0.04
citric acid 0.01 sorbitol 70% 22.00 FD + C green no. 3 0.0006
hydroxypropyl .beta.-cyclodextrin 5.00 sodium saccharin 0.05
benzoic acid 0.15 thymol 0.064 eucalyptol 0.092 menthol 0.042
methyl salicylate 0.060 flavor 0.10 purified water 71.8914 total
100.0000
EXAMPLE 2
[0047] A dental rinse was formulated by adding poloxamer, sodium
citrate, citric acid, sodium saccharin, hydroxypropyl
.beta.-cyclodextrin, sorbitol and dye to water, at room
temperature, using a Master Servodyne.RTM. mixer with high-lift
blade rotating at 200-300 rpm to give a clear aqueous solution.
Benzoic acid, menthol, thymol, methyl salicylate, eucalyptol and
flavor were added to the 190.degree. alcohol to give a clear
alcoholic solution. The alcoholic phase was added slowly to the
aqueous phase which was continually agitated until the addition was
complete. The resulting clear blue-green product was mixed for a
further 30 minutes. The product had a pH of approximately 4.0.
2 Ingredient Weight Percent poloxamer 407 0.50 sodium citrate 0.04
citric acid 0.01 sorbitol 70% 22.00 FD + C green no. 3 0.0006
hydroxypropyl .beta.-cyclodextrin 1.0 sodium saccharin 0.05 alcohol
190 proof 12.00 benzoic acid 0.15 thymol 0.064 eucalyptol 0.092
menthol 0.042 methyl salicylate 0.060 flavor 0.10 purified water
63.8914 total 100.0000
EXAMPLE 3
[0048] A dental rinse was formulated by adding poloxamer, sodium
citrate, citric acid, sodium saccharin, hydroxypropyl
.beta.-cyclodextrin, sorbitol and dye to water using a Master
Servodyne.RTM. mixer with high-lift blade rotating at 200-300 rpm
to give a clear aqueous solution. Benzoic acid, triclosan (Irgacare
MP--Ciba Geigy) and flavor were added to the 190.degree. alcohol to
give a clear alcoholic solution. The alcoholic phase was added
slowly to the aqueous phase which was continually agitated until
the addition was complete. The resulting clear blue-green product
was mixed for a further 30 minutes. The product had a pH of
approximately 4.0.
3 Ingredient Weight Percent poloxamer 407 0.50 sodium citrate 0.04
citric acid 0.01 sorbitol 70% 22.00 FD + C green no. 3 0.0006
hydroxypropyl .beta.-cyclodextrin 2.50 sodium saccharin 0.05
alcohol 190 proof 8.00 benzoic acid 0.15 triclosan 0.10 flavor 0.10
purified water 66.5494 total 100.0000
EXAMPLE 4
[0049] A dental rinse was formulated by adding poloxamer, sodium
citrate, citric acid, sodium saccharin, hydroxypropyl
.beta.-cyclodextrin, sorbitol and dye to water, at room
temperature, using a Master Servodyne.RTM. mixer with high-lift
blade rotating at 200-300 rpm to give a clear aqueous solution.
Benzoic acid, menthol, thymol, methyl salicylate, eucalyptol and
flavor were added to the 190.degree. alcohol to give a clear
alcoholic solution. The alcoholic phase was added slowly to the
aqueous phase which was continually agitated until the addition was
complete. The resulting clear blue-green product was mixed for a
further 30 minutes. The product had a pH of approximately 4.0.
4 Ingredient Weight Percent poloxamer 407 0.50 sodium citrate 0.04
citric acid 0.01 sorbitol 70% 22.00 FD + C green no. 3 0.0006
hydroxypropyl .beta.-cyclodextrin 1.25 sodium saccharin 0.05
alcohol 190 proof 8.00 benzoic acid 0.15 thymol 0.064 eucalyptol
0.092 menthol 0.042 methyl salicylate 0.060 flavor 0.10 purified
water 67.6414 total 100.0000
EXAMPLE 5
[0050] A dental rinse was formulated by adding poloxamer, sodium
citrate, citric acid, sodium saccharin, hydroxypropyl
.beta.-cyclodextrin, zinc chloride, sorbitol and dye to water using
a Master Servodyne.RTM. mixer with high-lift blade rotating at
200-300 rpm to give a clear aqueous solution. Benzoic acid,
menthol, thymol, methyl salicylate, eucalyptol and flavor were
added to the 190.degree. alcohol to give a clear alcoholic
solution. The alcoholic phase was added slowly to the aqueous phase
which was continually agitated until the addition was complete. The
resulting clear blue-green product was mixed for a further 30
minutes. The product had a pH of approximately 4.0.
5 Ingredient Weight Percent poloxamer 407 0.50 sodium citrate 0.04
citric acid 0.01 sorbitol 70% 22.00 FD + C green no. 3 0.0006
hydroxypropyl .beta.-cyclodextrin 1.25 zinc chloride 0.10 sodium
saccharin 0.03 alcohol 190 proof 8.00 benzoic acid 0.15 thymol
0.064 eucalyptol 0.092 menthol 0.042 methyl salicylate 0.060 flavor
0.10 purified water 67.5614 total 100.0000
EXAMPLE 6
[0051] A gel dentifrice was formulated by dispersing carboxymethyl
cellulose in the glycerin and polyethylene glycol using a
Lightening mixer. NaF was dissolved separately in the water. Water
and sorbitol were added and mixed for 25 minutes sodium saccharin
and hydroxypropyl .beta.-cyclodextrin were then added and mixed for
a further 10 minutes. The phenolics were mixed together, i.e.
eucalyptol, methyl salicylate, thymol and menthol, to make a
phenolic phase. The phenolic phase was added to the
cellulose/sorbitol/cyclodextrin/water phase until the phenolics are
dissolved. Sylodent.RTM. 700, Sylox.RTM. 2, FD+C Blue No. 1 and
sodium lauryl sulfate were then added and mixed thoroughly for 30
minutes. The resulting clear blue gel was deaerated to remove air
bubbles.
6 Ingredient Weight Percent glycerin 14.000 sorbitol, 70% 27.343
carboxymethyl cellulose, 9M8 0.900 polyethylene glycol, PEG-8 3.000
purified water 13.429 FD + C blue no. 1 0.005 hydroxypropyl
.beta.-cyclodextrin 15.000 sodium saccharin 0.500 NaF 0.243
Sylodent .RTM. 700 14.000 Sylox .RTM. 2 8.000 thymol 0.640
eucalyptol 0.920 menthol 0.420 methyl salicylate 0.600 sodium
lauryl sulfate 1.000
* * * * *