U.S. patent application number 13/625328 was filed with the patent office on 2013-01-17 for antiplaque oral care compositions.
This patent application is currently assigned to COLGATE-PALMOLIVE COMPANY. The applicant listed for this patent is COLGATE-PALMOLIVE COMPANY. Invention is credited to Thomas J. Boyd, Abdul Gaffar, David B. Viscio, Guofeng Xu.
Application Number | 20130017237 13/625328 |
Document ID | / |
Family ID | 36932115 |
Filed Date | 2013-01-17 |
United States Patent
Application |
20130017237 |
Kind Code |
A1 |
Boyd; Thomas J. ; et
al. |
January 17, 2013 |
ANTIPLAQUE ORAL CARE COMPOSITIONS
Abstract
The invention provides oral compositions including a safe and
effective amount of a compound represented by the formula (I):
##STR00001## wherein R.sup.1 and R.sup.2 are independently selected
from a hydrogen atom and an alkyl group and X' is an anion, and n
is an integer of 1 to 25; and (b) a surfactant.
Inventors: |
Boyd; Thomas J.; (Metuchen,
NJ) ; Xu; Guofeng; (Plainsboro, NJ) ; Gaffar;
Abdul; (Princeton, NJ) ; Viscio; David B.;
(Prescott Valley, AZ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
COLGATE-PALMOLIVE COMPANY; |
New York |
NY |
US |
|
|
Assignee: |
COLGATE-PALMOLIVE COMPANY
New York
NY
|
Family ID: |
36932115 |
Appl. No.: |
13/625328 |
Filed: |
September 24, 2012 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11375346 |
Mar 14, 2006 |
8287843 |
|
|
13625328 |
|
|
|
|
10875059 |
Jun 23, 2004 |
|
|
|
11375346 |
|
|
|
|
10601478 |
Jun 23, 2003 |
|
|
|
10875059 |
|
|
|
|
10601473 |
Jun 23, 2003 |
|
|
|
10601478 |
|
|
|
|
10601477 |
Jun 23, 2003 |
|
|
|
10601473 |
|
|
|
|
10601474 |
Jun 23, 2003 |
|
|
|
10601477 |
|
|
|
|
Current U.S.
Class: |
424/401 ; 424/49;
424/55 |
Current CPC
Class: |
A61Q 11/00 20130101;
A61K 8/44 20130101 |
Class at
Publication: |
424/401 ; 424/49;
424/55 |
International
Class: |
A61K 8/43 20060101
A61K008/43; A61Q 11/00 20060101 A61Q011/00; A61K 8/02 20060101
A61K008/02 |
Claims
1. An oral care composition comprising: (a) a safe and effective
amount of a compound represented by the formula (I): ##STR00004##
wherein R.sup.1 and R.sup.2 are independently selected from a
hydrogen atom and an alkyl group and X.sup.- is an anion, and n is
an integer of 1 to 25: (b) a surfactant; and (c) a silica compound
coated with a fatty acid.
2. The composition of claim 1, wherein the composition is free of a
monohydric alcohol.
3. The composition of claim 1, wherein R.sup.1 is an alkyl group
having 1 to 25 carbon atoms, R.sup.2 is an alkyl group having 1 to
50 carbon atoms and n is an integer of 1 to 10.
4. The composition of claim 1, wherein R.sup.1 is an alkyl group
having 1 to 8 carbon atoms, R.sup.2 is an alkyl group having 1 to
30 carbon atoms and wherein n is 3.
5-8. (canceled)
9. The composition of claim 1, wherein X.sup.- is selected from a
hydrochloride anion, a sulfate anion, an acetate anion, a tartarate
anion, and a citrate anion.
10. The composition of claim 1 wherein the compound is the
hydrochloride salt of ethyl lauroyl arginine.
11. The composition of claim 1, wherein the compound is present at
a concentration of about 0.02% to about 2% by weight of the
composition.
12. The composition of claim 1, wherein the compound is present at
a concentration of about 0.05% to about 25% by weight of the
composition.
13. The composition of claim 1, wherein the surfactant is selected
from a nonionic surfactant and a zwitterionic surfactant.
14. The composition of claim 1, further comprising a polyhydric
alcohol humectant.
15. The composition of claim 1, wherein the composition further
comprises an uncoated abrasive.
16. The composition of claim 15, wherein the uncoated abrasive is
selected from a silica compound, perlite, pumice, calcium
carbonate, polymer particulates, and precipitated silica.
17-18. (canceled)
19. The composition of claim 1 having a form selected from a
tablet, a lozenge, a confectionary, a chewing gum, a paste, a
powder, a gel, a semi-solid stick, a spray, a film, a bead, a
flake, a speckle, and a liquid.
20. The composition of claim 1, wherein the composition further
comprises a solid base and a sweetener.
21. The composition of claim 1, wherein the composition is in the
form of a film and further comprises a film-forming polymer
selected from a water soluble film-forming polymer and a
dispersible film-forming polymer.
22. The composition of claim 21, wherein the polymer is selected
from a hydroxyalkyl cellulose polymer and a hydroxymethylpropyl
cellulose.
23. The composition of claim 21, wherein the polymer is present in
the composition in a concentration of about 10% to about 60% by
weight of the composition.
24. The composition of claim 1, further comprising a metal
salt.
25. The composition of claim 1 claim 24, wherein the metal salt is
selected zinc gluconate and zinc citrate.
26. The composition of claim 1, wherein the fatty acid is selected
from the group consisting of ricinoleic acid and stearic acid.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of each of the
following: U.S. patent application Ser. No. 10/601,473, U.S. patent
application Ser. No. 10/601,474, U.S. patent application Ser. No.
10/601,477, U.S. patent application Ser. No. 10/601,478, each filed
Jun. 23, 2003; and U.S. patent application Ser. No. 10/875,059,
filed Jun. 23, 2004; the contents of each of which are incorporated
herein by reference.
BACKGROUND OF THE INVENTION
[0002] Dental plaque is present to some degree in the form of a
film on virtually all dental surfaces. It is a byproduct of
microbial growth, and comprises a dense microbial layer consisting
of a mass of microorganisms embedded in a polysaccharide matrix. It
is reported that plaque adheres firmly to dental surfaces and is
removed only with difficulty even through a rigorous brushing
regimen. Moreover, plaque rapidly reforms on the tooth surface
after it is removed. Plaque may form on any part of the tooth
surface, and is found particularly at the gingival margin, in
cracks in the enamel, and on the surface of dental calculus. The
problem associated with the formation of plaque on the teeth lies
in the tendency of plaque to build up and eventually produce
gingivitis, periodontitis and other types of periodontal disease,
as well as dental caries, bad breath (halitosis) and dental
calculus.
[0003] As plaque is formed by oral bacteria, a wide variety of
antibacterial agents have been proposed to retard plaque formation
and the oral infections associated with plaque formation. For
example, halogenated hydroxydiprrehyl ether compounds such as
triclosan are well known to the art for their antibacterial
activity and have been used in oral compositions to counter plaque
formation by bacterial accumulation in the oral cavity. However,
these antibacterial agents which work to reduce plaque formation by
temporary reduction in the population of oral bacteria have
numerous disadvantages when incorporated into commercial products,
including disadvantages stemming from production costs and
logistics, regulatory frameworks of various jurisdictions,
stability of commercially acceptable formulations, etc.
[0004] Thus, there remains a need in the art for oral compositions
that reduce or prevent plaque formation.
BRIEF SUMMARY OF THE INVENTION
[0005] The invention provides oral compositions including a safe
and effective amount of a compound represented by the formula
(I):
##STR00002##
wherein R.sup.1 and R.sup.2 are independently selected from a
hydrogen atom and an alkyl group and X' is an anion, and n is an
integer of 1 to 25; and (b) a surfactant.
DETAILED DESCRIPTION OF THE INVENTION
[0006] The invention provides an oral care composition that
contains the compound represented by formula (I):
##STR00003##
wherein R.sup.1 and R.sup.2 are independently selected from a
hydrogen atom and an alkyl group.
[0007] In various embodiments, R.sup.1 is independently selected
from an alkyl group 1 to 25 carbon atoms, preferably 1 to 8 carbon
atoms, most preferably 2, 3, 4, 5, 6, or 7 carbon atoms. In various
embodiments, R.sup.2 is may be an alkyl group having 1 to 50 carbon
atoms, preferably 1 to 30 carbon atoms. The symbol "n" may be an
integer of 1 to 10, preferably n is 3.
[0008] The group X' may be an anion such that resultant ester salts
is, for example, a an inorganic acid salt such as a hydrochloride,
or a sulfate or an organic salt such as acetate, tartarate or
citrate.
[0009] In various embodiments, R.sup.2CO may be derived from a
natural system mixed fatty acid residue such as coconut oil fatty
acids, tallow fatty acids, or a mono-fatty acid residue such a
lauroyl, myristyl, stearoyl and the like, the lauroyl group being
preferred.
[0010] Examples of antibacterial ester compounds preferred in the
practice of the present invention are antibacterial ester compound
of Formula (I) include N-alpha-cocoyl-L-arginine propyl ester, N
alpha stearoyl-L-arginine methyl ester, N steaoryl-L-arginine ethyl
ester hydrochloride. The term "cocoyl" is an abbreviation for
coconut oil fatty acid residue, and chloride salts of these ester
compounds hereinafter being referred to as arginine derivative
compounds. The salt of the arginine derivative compound, ethyl
lauroyl arginine, may be preferred for use in the practice of the
present invention.
[0011] The oral composition of the invention includes a
surfactant(s). Any known or to be developed in the art may be used,
and the nature, ratio and content of the surfactant(s) used may be
modified depending ion the specific end product desired. Nonionic
surfactants useful in the present invention include condensates of
sorbitan esters of fatty acids with ethylene oxide (polysorbates)
such as sorbitan mono-oleate with from about 20 to about 60 moles
of ethylene oxide and polysorbates. Zwitterionic surfactants that
may be used include betaine surfactants and those disclosed in U.S.
Pat. No. 5,180,577, incorporated herein by reference, alkyldimethyl
betaines, such as decyl betaine 2-(N-decyl-N,N-dimethylammonio)
acetate, cocobetaine or 2-(N-coc-N, N-dimethyl ammonio) acetate,
myristyl betaine, palmityl betaine, lauryl, betaine, cetyl betaine,
cetyl betaine, stearyl betaine, etc. The amidobetaines are
exemplified by cocoamidoethyl betaine, cocoamidopropyl betaine,
laurmidopropyl betaine and the like.
[0012] Surfactants useful in the practice of the present invention
include nonionic and zwitterionic surfactants. Suitable nonionic
surfactants useful in the present invention include
poly(oxyethylene)-poly(oxypropyle-ne) block copolymers. Such
copolymers are known commercially by the non-proprietary name of
poloxamers, which name is used in conjunction with a numeric suffix
to designate the individual identification of each copolymer.
[0013] Poloxamers may have varying contents of ethylene oxide and
propylene oxide which results in poloxamers which have a wide range
of chemical structures and molecular weights.
[0014] The surfactants may be present in any amount. Preferred
amounts are about 0.1% to about 5% by weight or about 0.6% to about
2.0% by weight.
[0015] The composition may contain an abrasive, such as, for
example, a silica compound, perlite, pumice, calcium carbonate,
calcium carbonate, polymer particulates, dicalcium phosphate,
alumina and precipitated silica. If a silica compound is selected,
it may be one or more of the silicas known or developed in the art
for use in various consumer products, such as a precipitated silica
and/or a surface modified silica. The silica may be a silica coated
with a glyceride of a fatty acid, for example, ricinoleic acid or
the acids of castor oil.
[0016] Other silica abrasives that may be useful in the practice of
the present invention include silica gels and precipitated
amorphous silicas. These silicas are colloidal particles having an
average particle size ranging from about 3 microns to about 12
microns, and more preferably between about 5 to about 10 microns
and a pH range from 4 to 10 preferably 6 to 9 when measured as a 5%
by weight slurry.
[0017] Illustrative of silica abrasives useful in the practice of
the present invention are marketed under the trade designation
SYLODENT.RTM. XWA by Davison Chemical Division of W. R. Grace &
Co., Baltimore, Md. 21203. SYLODENT.RTM. 650 XWA, a silica hydrogel
composed of particles of colloidal silica having a water content of
29% by weight averaging from about 7 to about 10 microns in
diameter.
[0018] Other abrasives used in the practice of the present
invention may include precipitated silicas having a mean particle
size of up to about 20 microns, such as ZEODENT.RTM. 115, marketed
by J. M. Huber Chemicals Division, Havre de Grace, Md. 21078, or
SYLODENT.RTM. 783 marketed by Davison Chemical Division of W. R.
Grace & Company.
[0019] The silica abrasive materials may be used individually as
the sole abrasive in preparing the dental composition of the
present invention or in combination with other known dentifrice
abrasives such as sodium metaphosphate, dihydrated dicalcium
phosphate, calcined alumina. The total quantity of abrasive present
in the dentifrice compositions of the present invention is at a
level of from about 5% to about 60% by weight, preferably from
about 10% to about 55% by weight when the dentifrice composition is
a toothpaste.
[0020] The ethoxylated hydrogenated castor oils used to precoat the
silica compounds prior to their incorporation into the dentifrice
of the present invention are prepared by hydrogenating castor oil
and treating the hydrogenated product with from about 10 to about
200 moles of ethylene glycol. These ethoxylated hydrogenated castor
oils are known by the non-proprietary name of PEG hydrogenated
castor oils, in accordance with dictionary of the Cosmetics,
Toiletries and Fragrance Association, 3rd Edition which name is
used in conjunction with a numeric suffix to designate the degree
of ethoxylation of the hydrogenated castor oil product, i.e., the
number of moles of ethylene oxide added to the hydrogenated castor
oil product. Suitable PEG hydrogenated castor oils include, PEG 16,
20, 25, 30, 40, 50, 60, 80, 100, and 200. In a preferred
embodiment, the PEG 40 hydrogenated castor oil surfactant is
CREMAPHOR RH40, a commercially available product from
BASF-Wyandotte, Parsippany, N.J. Ethoxylated hydrogenated castor
oil is coated on the silica compounds used in the preparation of
the compositions of the present invention at a castor oil to silica
weight ratio of about 1:10 to 1:2.
[0021] In some embodiments, it may be desirable to prepare a
composition that does not contain a monohydric alcohol.
[0022] The compositions of the invention may contain numerous and
varied other ingredients and may be in different delivery forms.
For example, the composition may take the form of a tablet, a
suspension, and emulsion, a lozenge, a confectionary, a chewing
gum, a paste, a powder, a gel, a semi-solid stick, a spray, a film,
a bead, a flake, a speckle, and a liquid.
[0023] If the composition is in the form of a film, it may contain
a film forming polymer, such as a water soluble film forming
polymer and a dispersible film-forming polymer. Such polymers may
include any known/developed in the art. Suitable polymers may
include polyvinyl pyrrolidone, hydroxyethyl cellulose,
hydroxypropyl methyl cellulose, hydroxyalkyl celluloses such as
hydroxypropyl cellulose, carboxymethyl cellulose, starch, polyvinyl
alcohol, sodium alginate, alginate esters, guar gum, xanthan gum,
gelatin, polyethylene oxide, polyethylene glycol, carrageenan,
pullulan, locust bean gum as well as water dispersible polymers
such as polyacrylates, carboxyvinyl copolymers, methyl methacrylate
copolymers and polyacrylic acid. Specifially, one may prefer a
hydropropylmethyl cellulose polymer (29.1% methoxyl groups and 9%
hydroxyproxyl group substitution) having a viscosity of about 1 to
about 40 millipascal seconds (mPa.$) as determined as a 2% by
weight aqueous solution of the HPMC at 20.degree. C. using a
Ubbelohde tube viscometer.
[0024] Preferably the selected polymer has a viscosity of about 1
to about 50 or 3 to about 20 mPa-s at 20.degree. C.
[0025] The polymer may be incorporated in the film composition in
amounts ranging from about 10 to about 60% by weight and preferably
about 15 to about 40% by weight.
[0026] The composition may be in the form of a confectionary, such
as a chewing gum or lozenge. If the form of a gum is desired, gum
base materials suitable for use in the practice of this invention
are well known in the art and include natural or synthetic gum
bases or mixtures thereof Representative natural gums or elastomers
include chicle, natural rubber, jelutong, balata, guttapercha,
lechi caspi, sorva, guttakay, crown gum, perillo, or mixtures
thereof Representative synthetic gums or elastomers include
butadiene-styrene copolymers, polyisobutylene and
isobutylene-isoprene copolymers.
[0027] The gum base may be incorporated in the gum at a
concentration of about 10 to about 40% by weight and preferably
about 20 to about 35% by weight. If desired, plasticizing/softening
agents commonly used in chewing gum compositions are suitable for
use in this invention, including gelatin, waxes and mixtures
thereof in, for example, amounts of 0.1 to 5% by weight. Suitable
non-cariogenic gums include kappa carrageenan, carboxymethyl
cellulose, hydroxyethyl cellulose and the like.
[0028] If the form desired is a non-gum confenstionary, for example
a lozenge bead or tablet, one may include as a carrier such as a
non-cariogenic, solid water-soluble polyhydric alcohol (polyol)
(such as mannitol, xylitol, sorbitol, malitol), hydrogenated starch
hydrozylate, hydrogenated glucose, hydrogenated disaccharides or
hydrogenated polysaccharides, in an amount of about 85 to about 95%
by weight of the total composition. Emulsifiers such as glycerin,
and tableting lubricants may be included Suitable lubricants for
incorporation include vegetable oils such as coconut oil, magnesium
stearate, aluminum stearate, talc, starch and Carbowax.
[0029] The lozenge, bead or tablet may optionally be coated with a
material such as waxes, shellac, carboxymethyl cellulose,
polyethylene/maleic anhydride copolymer or kappa-carrageenan to,
for example, further increase the time it takes the tablet or
lozenge to dissolve in the mouth.
[0030] Other ingredients that may be included in the composition of
the invention include solid bases, sweeteners, sources of fluoride
ions, of zinc ion, of copper ions, of silver ions; zinc citrate,
zinc gluconate, additional anti-caries or antiadhesion agents,
anti-inflammatory agents, antiplaque agents, sweeteners,
flavorants, rheology modifiers, antitartar agents, humectants,
plasticizers, solvents, botanical agents and herbs.
EXAMPLES
Example I
Mouthrinse
[0031] A mouthrinse of the present invention having a pH of 5.0 was
prepared by dissolving in water each of the ingredients listed in
Table I below with agitation in a glass mixing vessel.
TABLE-US-00001 TABLE I Ingredient Wt. % Ethyl lauroyl arginate HCl
(ELAH) 0.1 Sorbitol 10.0 Glycerin 10.0 Propylene glycol 7.0
Polysorbate 20 0.8 Cocoamidopropyl betaine 0.8 Sodium saccharin
0.03 Flavor 0.10 Water Q.S.
[0032] After 9 months at room temperature, the ELAH concentration
was determined by Gas Chromatography-Mass Spectrometry to be
unchanged at 0.1% by weight.
[0033] Using this mouthrinse, a double blind randomized clinical
study was conducted in which 15 human subjects were asked to rinse
for one minute with either the mouthrinse in Example I or a
matching placebo (i.e., without ELAH) twice a day for 4 days while
forgoing all other maintenance oral hygiene. There was a
statistically significant reduction of 11.6% in plaque using the
mouth rinse of Table I. The results of the study are recorded in
Table II below.
TABLE-US-00002 TABLE II Clinical efficacy of an alcohol-free
mouthrinse Mouthrinse Mean QHI* (SD)** % Reduction relative to
placebo Placebo 2.51 (0.30) -- 0.1% ELAH 2.22 (0.22) 11.6** *QHI =
Quitley & Hein Index (Art recognized measure of plaque on
teeth) **Standard Deviation **Significant at the 95% confidence
level
Example II
Toothpaste
[0034] Toothpaste compositions containing ethyl lauroyl arginine
HCL (ELAH) were prepared having the following ingredients:
TABLE-US-00003 TABLE III Composition (Wt. %) Ingredients A B C
Polyethylene glycol 600 3 3 3 PEG-40 castor oil 6 6 0 Hydroxyethyl
cellulose 1.0 1.0 1.0 Xanthan 0.2 0.2 0.2 Sodium saccharin 0.35
0.35 0.35 Sodium fluoride 0.243 0.243 0.243 Sorbitol 40 40 40
Sodium hydroxide, 50% soln. 0.5 0.5 0.5 Titanium dioxide 0.5 0.5
0.5 ELAH 0.5 0 0.5 ZEODENT .RTM. 115 5 5 5 ZEODENT .RTM. 165 2 2 2
SYLODENT .RTM. XWA 650 15 15 15 Polysorbate 20 1 1 1 Cocomidopropyl
betaine 1 1 1 Flavor 0.72 0.72 0.72 Water to make 100 100 100
[0035] The dentifrice "Composition A" was prepared by dispersing
the sorbitol in the water in a conventional mixer under agitation.
Into the dispersion was added the xanthan, PEG-40 castor oil,
sodium fluoride, hydroxyethyl cellulose, and sodium saccharine. The
resultant mixture was agitated until a homogeneous gel phase was
formed. Into the gel phase was added TiO.sub.2 and sodium hydroxide
to adjust the pH to 6.5. These ingredients were mixed until a
homogenous phase was obtained. The mixture was then transferred to
a high speed/vacuum mixer; wherein the PEG-40 castor oil coated
silica compounds ZEODENT.RTM. 115, ZEODENT.RTM. 165, and
SYLODENT.RTM. XWA 650 were added and the mixture mixed at high
speed for 25 minutes, under vacuum from about 30 mm Hg. Finally,
polysorbate 20, cocoamidobetaine, flavor and ELAH were added to the
mixture and mixed for an additional 10 minutes. The resultant
product was a homogenous, semisolid, extrudable paste or gel
product.
[0036] For purposes of contrast, the procedure of the Example was
repeated to prepare Composition B with the exception that ELAH was
not included in the dentifrice formula. A second comparative
composition, Composition C, was also prepared following the
procedure of the Example with the exception that neither silica
abrasive ZEODENT.RTM. 115 (Composition A) or the silica abrasive
ZEODENT.RTM. 165 (Composition B) present in the dentifrice was
coated with the PEG-40 castor oil.
[0037] The stability of the ELAH present in the prepared dentifrice
composition A, B, C was measured by titrating a 0.015% wt. solution
of the dentifrice with a 0.005N solution of sodiym lauryl sulfate
(SLS). The recovery results are recorded in Table IV below.
TABLE-US-00004 TABLE IV Composition % Recovery ELAH A 87.1 B 3.0 C
7.5 ELAH (Palcebo) 102.8
[0038] The antiplaque activity of Composition C was assessed using
a flow cell model of the type disclosed in the Journal of Dental
Research, vol. 73(11), pp. 1748-1755 (1994). Pooled human saliva
was used as the bacterial source and single crystal geranium prisms
as the oral surface model. Prior to exposure to bacteria, the
surfaces were treated with a 2:1 dentifrice water slurry and then
rinsed with artificial saliva (1 part porcine mucin 25 g/L, and 1
part saliva buffer solution) for 30 minutes under 1 mL/min flow
conditions.
[0039] Composition A was assessed for overall plaque inhibition
versus the comparative Composition B which did not contain ELAH,
and Composition C in which the silica abrasive and thickener were
not precoated with PEG-40 castor oil. The compositions were
simultaneously run in the system. The lower plaque score the more
effective the antiplaque agent. The results recorded in Table V
below show a significant reduction in plaque effected by
Composition A when compared to comparative Compositions B and
C.
TABLE-US-00005 TABLE V Composition Plaque Index % reduction A
1.4237 17.5 B 1.7232 -- C 1.6705 3.2
[0040] The results recorded in Table V indicate that Composition A
containing the PEG-40 castor oil coated silica compounds was more
effective in plaque reduction than composition C which the silica
compounds were not coated with the PEG-40 castor oil as well as
Composition B which did not contain ELAH.
Example III
[0041] A series of films containing varying amounts of the arginine
derivative compound they hydrochloride salt of ethyl lauroyl
arginine designated Compositions A, B and C were prepared by using
the ingredients listed in Table VI below. In preparing the film,
the hydroxyl propylmethylcellulose polymer ingredient (Methocel
E5LV) and carrageenan as added at a temperature of 70.degree. C. to
90.degree. C., to half the amount of total deionized water used,
and the solution stirred for 20 minutes at a slow speed using IKA
Labortechnik Model RW2ODZMixer. The remaining amount of water
maintained at room temperature (21.degree. C.) was then added and
the mixing continued for 40 minutes. To this solution was added the
corn starch ingredient (Cerestar Polar Tex Instant 12640) and the
mixture stirred for an additional 20 minutes until the starch was
completely dispersed and a homogenous mixture was formed. To this
mixture was added sucralose and mixed for 10 minutes after which
the emulsifier Tween 80 was added and mixed for an additional 5
minutes. Thereafter, flavor was thoroughly mixed for an additional
30 minutes to form a flurry emulsion to which as a final step the
hydrochloride salt of ethyl lauroyl arginine HCL (ELAH) dispersed
in canola oil was slowly added until evenly dispersed in the film
ingredient slurry. The emulsion was then cast on a polyethylene
coated paper substrate and dried in a convection oven at
110.degree. C. to form a solid thin (30 to 60 .mu.m thick)
film.
[0042] For purposes of comparison, the procedure of Example III was
repeated to prepare a film composition designated Composition D
with the exception that no ethyl lauroyl arginine HCL was
incorporated in the film composition.
TABLE-US-00006 TABLE VI Composition (Wt. %) Ingredients A B C D
HPMC 41.0 41.0 38 41.0 Carageenan 0.50 0.50 0.50 0.50 Corn Starch
19.0 19.0 17 19.0 Flavor 25.0 25.0 18 25.0 Tween 80 2.30 2.30 2.1
2.30 Canola oil 4.50 4.50 4.1 4.50 Sucralose 1.4 1.4 1.3 1.4
Propylene glycol 1.25 6.25 11.5 0 ELAH 0.50 2.5 5.0 0 Water Q.S.
Q.S. Q.S. Q.S.
[0043] The antiplaque activity of Compositions A, B, C and D was
assessed using a flow cell model of the type disclosed in the
Journal of Dental Research, vol. 73(11), pp. 1748-1755 (1994) using
human saliva as the bacterial source and single crystal germanium
prisms as the oral surface model. After pretreatment of these
surfaces with a precisely cut strip (10 mm.times.20 mm), they were
rinsed with artificial saliva (1 part porcine mucin 25 g/L, and 1
part saliva buffer solution) prior to exposure to bacteria, and
exposed to treatment in the flow cell. The plaque index of the
deposits on the prisms was determined by infrared
spectrophotometry.
Plaque Score
[0044] Compositions A, B and C were assessed for overall plaque
inhibition versus the comparative Composition D which did not
contain an antibacterial agent which was simultaneously run in the
system. The lower the Plaque Index the more effective the
antiplaque agent. The results recorded in Table VII below show a
30-40% reduction in plaque effected by Film Compositions A, B and C
when compared to Folm Composition D.
TABLE-US-00007 TABLE VII Composition Plaque Index % reduction A
0.429 37.7 B 0.466 32.4 C 0.486 29.6 D 0.690 --
Example IV
[0045] A second series of film compositions designated E and F were
prepared following the procedure of Example I, in which Composition
E contained 5% by weight (dry film) ELAH, Composition F contained
5% by weight (dry film) ELAH and 1.5% by weight (dry film) zinc
gluconate. For purposes of comparison, film Composition G prepared
in the same manner as Film A but which contained no ELAH and Film
Composition H, a commercially available breath freshening film were
tested for antiplaque efficacy in the artificial mouth test model.
The tests were run in parallel under identical conditions wherein 4
hydroxyapatitie discs (HAP) disks were coated with pellicle for two
hours followed by additional 2 hours of bacteria attachment. The
disks were mounted in a flow cell and 10 .mu.mL solution of film
(containing 150 mg film) were then passed over the surface of the
disks for 1-2 minutes; water was passed over the disks for 10
minutes to wash. The flow cell was then connected to the artificial
mouth chemostat circulator and incubated for 8-12 hours. The
procedure was repeated 4 times, and thereafter the HAP disks were
dismounted and bacteria on the disks were detached. The bacteria
were quantified by optical density readings. The results of this
test procedure are recorded in Table VIII below.
TABLE-US-00008 TABLE VIII Optical Density Film Composition Mean
Standard Deviation % Reduction E 0.23 0.02 31.2 F 0.20 0.03 38.9 G
0.33 0.05 0 H 0.38 0.38 1.0
[0046] The results in Table VIII show that antibacterial films of
the present invention (Films E, F) effect a significant reduction
in antiplaque formation when compared to films G, H that did not
contain the arginine derivative compound.
Example V
[0047] The procedure of Example IV was repeated in which a series
of film compositions designated J, K were prepared following the
procedure of Example I in which Composition E contained 5% by
weight (dry film) ELAH, Composition L contained 5% by weight (dry
film) ELAH and 1.5% by weight (dry film) zinc gluconate. For
purposes of comparison, Composition M contained 5% by weight (dry
film) Triclosan, but no ELAH and Composition H was a placebo
containing no ELAH or antibacterial ester compound.
[0048] The antiplaque efficacy of the films was evaluated following
the artificial mouth model described in Example IV. The results of
these tests are recorded in Table IX below.
TABLE-US-00009 TABLE IX Optical Density Film Composition Mean
Standard Deviation % Reduction J 0.23 0.02 31.2 K 0.20 0.03 38.9 L
0.23 0.03 30.6 M 0.33 0.05 0.0
[0049] The results recorded in Table IX indicate that ELAH is at
least effective as Triclosan in reducing plaque formation when
delivered to the oral cavity from a consumable film and that a
combination of ELAH and a metal salt such as zinc gluconate
provides antiplaque efficacy superior to Triclosan.
Example VI
[0050] A series of film compositions designated Compositions N, P,
Q were prepared following the procedure of Example I, in which
Composition N contained 0.50 by weight ELAH, Composition P
contained 2.5% ELAH and Composition Q contained 5% by weight
ELAH.
[0051] For purposes of comparison film Composition R was also
prepared following the procedure of Example I except that no ELAH
was incorporated in the film composition.
[0052] Film Compositions N, P, Q and R were evaluated for breath
freshening efficacy by an in-vitro volatile sulfur compound (VSC)
reduction assay. In this assay a known amount of film is dissolved
in 3.0 milliliters (ml) of saliva in a glass vial. After incubation
at 37.degree. C. overnight, the headspace of the solution is
sampled and analyzed for the VSC. The VSC assay results are
presented in Table X below.
TABLE-US-00010 TABLE X VSC in the headspace Film Composition
Baseline After 24 hours VSC Reduction (%) N 27.3 23.90 12.5 O 27.3
18.36 32.8 Q 27.3 4.56 83.3 R 27.3 25.61 6.3
[0053] The VSC assay results recorded in Table X demonstrate the
increase in VSC reduction as the concentration of the antibacterial
ester ELAH in the film matrix is increased.
Example VII
TABLE-US-00011 [0054] TABLE XI Lozenge Ingredient Wt. % Saccharin
0.15 Magnesium Stearate 0.40 Glycerin 1.0 Ethyl lauroyl arginine
0.5 Flavor 2.0 Sorbitol Q.S
Example VIII
TABLE-US-00012 [0055] TABLE XII Bead Ingredient Wt. % Gelatin 30
Flavor 45 Vegetable oil 22.5 Aspartame 0.2 Ethyl lauroyl arginine 1
Food color 0.002 Flavor 2.0 Ethyl alcohol 0.3 Water Q.S.
Example IX
TABLE-US-00013 [0056] TABLE XIII Tablet Ingredient Wt. % Starch
coated dicalcium phosphate 40 Cellulose 20 Glycerin 12 Sorbitol 17
Sodium saccharin 0.2 Flavor 1 Lechithin 0.5 Ethyl lauroyl arginine
0.5 Water Q.S.
Example X
TABLE-US-00014 [0057] TABLE XIV Chewing Gum Ingredient Wt. % Gum
base 25 Binder 10 Aspartame 0.5 Ethyl lauroyl arginine 1 Flavor 2.0
Titanium dioxide 0.4 Sorbitol/maltitol (50:50) Q.S.
* * * * *