Note: Descriptions are shown in the official language in which they were submitted.
f~'8$~99~L
Description
Periodontal Composition and Method
Technical Field ~
This invention relates generally to periodontal compo- -
5 sitions and methods; and relates more specifically to composi-
tions and methods of this type which are capable of providing
active oxygen in the oral cavity, to thereby inhibit the motility
of harmful oral bacteria.
- Background Art
Recent developments in dental technology, coupled with
topical fluorides, sealants and fluoridization of municipal water
supplies, have fostered a remarkable decrease in tooth decay.
While laymen have associated decay with the main cause of tooth
loss, it is well-known to dental experts that the major cause of
tooth loqs after the age of 35, is in fact gum disease. Indeed,
gum disease has now reached epidemic proportions -- over 90% of ~ ;
the general population are considered by most such experts to
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Since gum disease is not painful, it is easily unde-
tected, and in consequence, untreated. Without the acute pain
associated with a toothache, most people indeed pay little or no
attention to their gums until the disease has reached an advanced
stage and they are threatened by the loss of teeth.
Recent studies and investigations, however, have con-
clusively demonstrated that the major cause of gum disease is
specific bacteria that live and thrive in the gum crevices.
These bacteria give off toxins that attack the bone, cementum and
gums which support the teeth. If one is able to eliminate the
cause (bacteria), the result is healing of the gums.
Dentists and periodontists have long known that certain
substances can exert powerful cleansing and sanitizing action on
the teeth, the gums and the oral cavity. Hydrogen peroxide, bak-
lS ing soda (sodium bicarbonate), and salt (sodium chloride) are
examples of such materials. The major recent proponent of an
anti-microbial method based on such knowledge, is Dr. Paul Reyes;
and indeed this new therapy is now widely recognized as the
"Keyes Technique".
..
Prior to the popularization of Dr. Keyes methodology
most periodontal cases were referred to periodontists, and the
method of treatment was often surgery (gingivectomy). This sur-
gery is expensive and painful. Because of the pain, suffering,
and expense associated with gum surgery, a rapidly growing num-
128~94
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ber of dentists are, however, now adopting the concept of Dr.
Keyes, and his non-surgical approach to gum disease.
Instead of a scalpel, Keyes relies on such ordinary
household items as salt, hydrogen peroxide and baking soda to
create a hostile climate for these troublesome bacteria. The
baking soda neutralizes the acidic toxins given off by the bac-
teria, and the peroxide effectively Icills the anerobic bacteria
that cause gum disease. The anerobic bacteria cannot survive in
an oxygenated environment.
Unfortunately baking soda and peroxide must be mixed
daily, because these two elements decompose rapidly when mixed
together. This is a messy, time-consuming and unpleasant daily
chore. As a result, it is very difficult for the potential bene-
ficiaries of such therapy to faithfully adhere to the regimen.
The Keyes method is e.g. described in an article by
Judith E. Randal in A.H. (March/April 1982), at pages 82-85, and
elsewhere. According to the procedure, once a day a patient is
required to perform the following routine:
(a) Two tablespoons or so of baking soda are wet with
enough hydrogen peroxide to form a thick paste;
(b) A rubber tip, of the kind found on some toothbrush
handles, is employed to massage the paste into the spaces between
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the teeth and at the gum margins on both the front and back sides
of the teeth;
(c) Again using the paste, the patient messages the
gums and gum margins front and back with an electric toothbrush
or a child-sized manual toothbrush;
td~ Enough salt is added to a glass of warm water so
that some remains in the bottom even when the solution is
stirred;
- (e) The liquid part of the mixture is poured into a
Water Pik~; and with the device set at moderate speed, the teeth
and gums, front and back are rinsed; and
(f) A glass of plain water is run through the Water
Pik~ to prevent salt damage to its internal parts.
As is readily apparent from the above description of
the Keyes method, it is a relatively complex and burdensome pro-
cedure for an individual patient to employ on a daily basis. It
would clearly be desirable for a patient to be able to perform
the Keyes method or a method similarly effective in an easier
manner, e.g., with a single composition.
However, merely combining the components employed by
Keyes into a "prepackaged" formula will not provide an effective ~-
means for accomplishing the desired results. Specifically, the
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hydrogen peroxide and/or sodium bicarbonate ca~n in a combination
decompose rapidly. Hydrogen peroxide (or other peroxide) can
break down in the presence of alkalinity, heat, light and/or
metal ions as follows:
2H202--~ 2H2 + 2~ (gas)
Similarly, sodium bicarbonate can break down in the presence of
hydrogen peroxide, heat and/or water as follows:
2NaHCO3 -~ Na2C3 + H2O + CO2~ (gas)
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Since the active materials are lost or diminished, such a formula
will have a short shelf life. Moreover, the gas evolution is
especially undesirable with a tooth paste or gel, since such gas
evolution can cause swelling and/or bursting of tubes or other
packages containing same. All of these factors are undesirable
for a consumer product.
Disclosure of Invention
:
Now in accordance with the present invention, a perio-
dontal composition is provided, which includes a peroxide and a
; bicarbonate, in a single highly stable form, which is therefore
susceptible to conventional modern packaging and dispensing sys-
tems, and which can be readily and effectively used by the con-
sumer.
The composition can be prepar-d as a non-aqueous paste
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or gel dentifrice, and generally comprises a water soluble, non-
aqueous vehicle having dispersed therein an orally acceptable
organic or inorganic peroxide; and a bicarbonate salt. The com-
position is substantially anhydrous, and the amounts and relative
proportions of the peroxide and bicarbonate are sufficient to
provide a level of bactericidally active oxygen upon breakdown
of the peroxide by tissue contact and by reaction with the
bicarbonate in the oral cavity of the user. The amount of the
bicarbonate is effective to provide a neutral or basic p~ upon
dissolution of the composition in water. The composition may be
contacted with water in mouth saliva, a moistened toothbrush, or
by contact with water from an oral irrigating device such as a
Water-Pik~. Also the composition can be directly disolved in a
volume of water to provide a mouth wash.
lS At least one of the peroxide or bicarbonate is provided
with a water-soluble barrier coating, which is, however, insolu-
ble in the non-aqueous vehicle, to prevent reaction therebetween
in the absence of water dissolution of the coating. All of the
components of the composition thus far referred to are water-
soluble, whereby upon the composition being contacted with sub-
stantial quantities of water, including in the oral cavity of a
user, dissolution of the barrier coating enables reaction of the
peroxide and bicarbonate to augment release of active oxygen, to
inhibit the motility of oral bacteria in said cavity. Dissolu-
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tion of the bicarbonate further, enables neutralizing of acidsecretions in the oral cavity.
The compositions of the invention may also include one
or more auxiliary stabilizers, which serve to further reduce the
possibility of premature decomposition of the peroxide, or of
premature raction between peroxide and bicarbonate components.
These can comprise e.g. dessicants which remove or absorb any
trace water which may find its way into the compositions. A pre-
ferred material for these purposes is colloidal pyrogenic silica,
which also serves in the composition as a thickener.
The compositions may also include small amounts of
normal dentrifice adjuvants, such as flavoring agents (typically
0.1 to 5~); cleansing and foaming agents (surfactants), typically
as 0.1 to 10%; normally acceptable dental abrasives or polishing
agents (preferably 1 to 15~, although higher amounts can be
used), such as dicalcium phosphate, suitable calcined kaolins,
etc.; sweetening agents, colorants and the like.
The compositlons may also include fluorine-containing
compounds as are known for use in the dentifrice art, such as
.
;~ ~ 20 sodium fluoride, sodium monofluorophosphate, stannous fluoride,
and the like.
In order to afford yet further stability to the compo-
sitions of the invention, the dentifrice adjuvants and fluorine-
containing compounds (if present), may be provided with water
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soluble barrier coatings, as described for the bicarbonate and/or
peroxide components.
8est Mode for Carrying Out the Inventlon
The peroxide component of the compositions of the
invention preferably comprises urea peroxide or hydrogen peroxide.
If the latter is used it should preferably be absorbed on an
orally acceptable inert particulate carrier, as for example a
kaolin, which can then be provided with a water soluble barrier
- coating.
The peroxide component of the compositions of the
invention is included in an amount sufficient to allow release of
sufficient oxygen when the composition is contacted with water,
e.g. during brushing of teeth, to inhibit the motility of oral
bacteria, e.g., in the treatment of gingivitis. Typically, the
peroxide can be employed in the composition of the present inven-
tion in amounts so that at least about 1% of the composition com-
; prises a peroxide. Preferably, the peroxide comprises from about
1 to about 20% by weight of the composition. More preferably,
the peroxide comprises from about 2 to about 5% by weight of the
composition. A typical peroxide concentration in the composition
is about 3% by weight. The active peroxide content (i.e., the
equivalent f ~22 in the peroxide employed) is prefe;ably
between about 0.5 and about 5% by weight, more preferably between
about 1 and about 3% by weight.
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The bicarbonate salts employed in the composition of
the invention include any which are sufficiently soluble so that,
when the composition is contacted with water, e.g., in the brush-
ing of teeth, a neutral or basic pH is provided by the bicarbo-
nate. Suitable bicarbonates include alkali metal and alkalineearth metal bicarbonates. Examples of suitable bicarbonates
include sodium bicarbonate, potassium bicarbonate, lithium bicar- -
bonate, calcium bicarbonate, magnesium bicarbonate, and the like
or mixtures thereof. A preferred bicarbonate is sodium bicarbo-
nate. If it is desirable, e.g., with a patient having high blood
pressure, etc., sodium-free compositions or low sodium composi-
tions can be employed, such as potassium bicarbonate or magnesium
bicarbonate. Combinations of bicarbonate salts can also be
employed, e.g. sodium and potassium bicarbonates.
The bicarbonate is included in the composition of the
invention in an amount sufficient to provide a neutral and basic
pH when the composition is contacted with water, (as is in the
oral cavity), preferably a pH of from about 7.0 to about 9.5.
The amount of bicarbonate actually employed in the method of the
invention can vary greatly depending upon the form of the compo-
sition and its intended method of application. The bicarbonate
preferably comprises from about 1 to about 20% by weight of the
composition in a tooth paste or gel, more preferably from about 2
to about 8% by weight.
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of the bicarbonate and peroxide components of the pre-
sent compositions, preferably at least the bicarbonate is pro-
vided with the water soluble barrier coating. Alternatively the
peroxide alone may be the member so provided; or to achieve still
greater stability, both members can be provided with the said
coating.
As mentioned, the water soluble barrier coatings can
also be provided on desired species of the dentifrice adjuvants
when such are present -- for example, upon particulate surfac-
tants such as sodium lauryl sulfate, upon dental abrasives or
polishing agents such as dicalcium phosphate, upon fluorine-con-
taining compounds, flavorings, colorants, etc. This in order to
minimiæe any detrimental effects which such adjuvants might
.,
otherwise have upon the stability of the present compositions.
While not as important a factor where the bicarbonate
is provided with a barrier coating, it has nonetheless been found
in the present invention that by increasing the particle size of
the bicarbonate salt, which decreases its surface area, the
stability of the peroxide in the compositions of the invention is
increased. For example, as among grade numbers l, 2 and 5 baking
soda available from Allied Chemical (Bulletin No. 513-016 U.S.A.),
the No. 5 grade provides the greatest peroxide stability in the
composition of the invention, while the No. 2 grade provides
almost the same stability. Preferably, the particle size of the
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bicarbonate salt is such that it provides a residual peroxide
level of from about 95 to about 99%~ more preferably, from about
97.5 to about 99%~ when the composition is stored in a closed
container at room temperature for about 6 weeks. Typical screen
5 analysis of such grades of baking soda are set forth below:
Grade Baking Soda
Screen
Analysis No. 1 No. 2 No. 5
Cumulative ~ on
10 U.S. No. 60
trace 37
100 1 1 72
170 25 68 98
200 38 89 100
325 71 99
Bulk
~ensity
(lb/ft3) 53 55 46
~Preferably, the bicarbonate employed in the composition
of the present invention has an average particle size of from
about 100 to about 2,000 microns, more preferably from about 200
to about 800 microns.
The surface area of the bicarbonate particles in the
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composition of the invention can be further reduced by agglom-
erating the particles to form aggregates with less surface area
than the component particles. These aggregates can in turn be
coated. Aggregation and coating can also be conducted simul-
taneously or in sequence. Agglomeration can be accomplished byvarious means. For example, the bicarbonate salt particles can
be mixed together with, for example, a polyethylene glycol of
suitable molecular weight. Depending upon the amount of poly-
ethylene glycol employed, the resulting material can be in the
form of agglo~erated particles or in the form of a thick and
extrudable paste. In the case of such a paste, the paste like
material can be extruded into thin strips and then cut into
small pellets containing agglomerated particles of the bicarbo-
nate salt. Such agglomerated sodium bicarbonate salt particles
preferably have an average particle size in the range of from
about lnO to about 2,000 microns and can be used in the same
manner as the normal bicarbonate salt in the compositions of the
invention.
It should be pointed out here that relatively small
amounts of chemical decomposition of the peroxide and/or bicarbo-
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~L2~6994
nate during storage can give rise to large amounts of gases
(oxygen and/or carbon dioxide) which can cause a closed container
such as a tooth paste tube to swell or even explode. It has been
found that in the absence of the barrier coating and/or auxiliary
stabilizer used in the present invention such gas evolution does,
in fact, take place and can cause such swelling, etc. The pre-
sent invention overcomes this problem by including a suitable
stabilizer -- i.e. a barrier coating -- which prevents breakdown
of the peroxide and/or bicarbonate.
- - 10 The barrier coating preferably comprises a water-solu-
ble, edible and non-toxic polymer or gum. Edible and water solu-
ble plant gums and mucilages are generally suitable for the fore-
going purposes. Heteropolysaccharides are the predominant con-
stituents of these latter products. Among such useable natural
gums and mucilages are guar gum, xanthate gum, gum arabic, and
gum tragacanth. Also utilizable are locust bean gum and carob
bean gum as well as gelatin, pectin, and cellulose derivatives
such as Klucel0. ~igh molecular weight polyethylene glycols are
also suitable, such as the products of this type sold under the
trademarks CARBoWAX by Union Carbide.
:
~ urther, synthetic polymers having the aforementioned
properties can also be used. These include cellulosic polymers
such as methyl cellulose and carboxy methyl cellulose of appro-
priate molecular weights; as well as other similar cellulosic
polymeric compounds.
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In a presently preferred form of barrier coating, an
edible non-toxic water soluble starch or starch-like polymer or a
gum is coated upon at least the bicarbonate, so as to effectively
form a barrier layer or protective shielding about the particles
of same. Typically, the said coating comprises from about 1 to
30~ by weight of the bicarbonate, more preferably from about 5 to
15~, and still more preferably about 10% by weight of the bicar-
bonate. A suitable starch-coated product of this type is avail-
able from Durkee Corporation under product designations such as
- 10 "ML 90". These commercially available products constitute sodium
bicarbonate coated with a water soluble malto-dextrin (partially
broken down), and have heretofore found use as leavening in the ~-
baking industry.
-
More generally, starches are natural polysaccharides, -
which are usually regarded as homopolysaccharides. A typical ;~
starch is thus a cryst polymeric compound consisting of about 27%
linear polymer (amylose) and 73~ brancad polymer (amylopectin).
By hydrolysis, derivatives are obtained, such as the mentioned
malto-dextrin, amylodextrin, or amylogen etc., which are referred
to as "water soluble starches", and which are utilizable as the
present barrier coatings.
: .:
Commercially, water soluble starches of this type are
available under such tradenames as CAPSUL, STARCH 46, and N-LOK,
all of these being products of National Starch Company.
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The barrier coating can be provided alternatively upon
the peroxide component, or can be provided on both peroxide and
bicarbonate. Where the peroxide is a solid powder such as the
preferred urea peroxide, the coating may be directly applied.
Where a normally liquid peroxide is used, i.e. such as hydrogen
peroxide, the latter is first sorbed on an inert carrier such as
a kaolin, which is then coated with the barrier coating. The
amount of coating material where same is applied to the peroxide
component is typically in the ranges indicated for the coatings
` 10 on the bicarbonate.
It should be understood that the barrier coatings of
the present invention, depending upon the mode of application
upon the protected species, may encapsulate the latter, or may
form a protective coating by being clustered about the particles
of the protected species. In any event, the active species is
thereby covered by the coating and effectively isolated from
undesired interactions, until released by water disrupting the
said barrier.
The provision of a barrier coating upon the active
~0 species can be carried out by numerous known methodologies.
Typically, the actives in the form of powders, for example,
sodium bicarbonate and/or urea peroxide can be so coated while
suspended in air in a fluidized bed procedure. The coatings may
be applied in the form of a solution (aqueous, non-aqueous or
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394
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hydroalcoholic) or as a melt -- that is sprayed on the particles
to be coated. Among the major types of spraying procedures which
can be so used are top spraying; Wurster spraying or rotor spray-
ing. Details of suitable coating methodology can be found in a
commercial brochure published by the Glatt Company of Ramsey,
New Jersey, which is authored by Mehta and Jones and entitled
"Coated Pellets Under the Microscope". In the top spray method,
the coating solution is sprayed downwardly onto the substrate as
it is fluidized by air flowing from below.
Coating of the active species with the barrier coating
can also be effected by other generally known methods. Thus, for
example, the actives in the form of dry powders (e.g. sodium
bicarbonate, urea peroxide) can be dry mixed or rolled with the
gum or polymer. It is also possible to melt the polymer or gum
and coat the actives by spraying or rolling or intermixing.
Melting e.g. can also be used to apply coatings of sugars
(sucrose and dextrose), dry sorbital and powdered mannitol.
Where particulate dentifrice adjuvants are to be simi-
larly provided with barrier coatings (e.g. foaming agents, sur-
factants such as sodium lauryl sulfate or dental abrasives suchas dicalcium phosphates, flavorings, fluorine compounds, color-
ants, etc.), the same techniques may be used for providing the
coating -- notably spraying the coating onto the suspended parti-
culates in a fluidized bed.
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The hydrophilic, non-aqueous vehicles employed in the
tooth paste or gel composition of the present invention are water
soluble so that they facilitate the action of the bicarbonate and
peroxide during brushing with the composition. Thus, the vehi-
cles employed in the present invention preferably rapidly dis-
solve with water when used by a consumer, e.g., in mouth rinse
water or the water in a pre-moistened toothbrush in saliva, or in
the post-brushing water rinse. The active species, i.e., the
peroxide and bicarbonate salt, may be dispersed, or suspended in
the vehicle.
Suitable hydrophilic, non-aqueous vehicles for use in
the present invention include polyalkylene glycols, non-ionic
surfactants, anionic surfactants, ampholytic surfactants, cati-
onic surfactants and alkanolamides. Also suitable are glycerol,
propylene glycol or sorbitol in combination with silica, clay,
polymer and/or gum thickeners, and perhaps dicalcium phosphate as
a cleansing agent.
The hydrophilic, non-aqueous vehicles preferably pro-
vide a viscosity for the composition suitable for its use as a
toothpaste or gel, e.g. between about 2,000 cps. to about 200,000
cps. If the selected vehicle does not itself provide the desired
viscosity, viscosity modifiers, such as barrier coated dicalcium
phosphate, finely divided pyrogenic silica and the like may be
added, and/or other known and orally acceptable vehicle agents
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can be included to provide such desired viscosity.
Typically, the hydrophilic, non-aqueous vehicles
employed in the tooth paste or gel compositions of the invention
are present in an amount of from about 45 to about 90% by weight.
Preferably, the vehicles are present in an amount of from about
85 to about 9o%.
Suitable polyalkylene glycols for use as vehicles in
the present composition include those having molecular weights of
from about 200 to about 20,000. Such materials range in physical
state from thin liquids to pastes to solids with increasing mole-
cular weight.
- Preferred polyalkylene glycols for use as vehicles in
the present invention are polyethylene glycols having the general
formula H(OCH2CH2)nOH, where n is greater than or equal to 4.
These liquid and solid polymers are widely known and available
under trademarks such as Carbowax~ (Union Carbide). In general,
each polyethylene glycol ~PEG) is identified by the manufacturer
by a number which corresponds to its average molecular weight,
e.g. "Carbowax~ 400". Preferred PEG's for use in the present
invention have a molecular weight in the range of from about 400
to about 8,000. Mixtures of such polyethylene glycols of differ-
ing molecular weights (and for that matter other vehicles dis-
cussed herein) can be employed to provide desirable viscosity
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~2~6994
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characteristics for the composition.
Other suitable polyalkylene glycol vehicles include
materials of the formula
CH3 fH3 fH3
5HO-CH-CH2O(CH2CHO)nCH2CH-OH
or
HO(CH2CH20)a (CHcH20)b (CH2CH20)c~
CH3
wherein n, a, b and c are integers such that the molecular
weights of such materials are in the range of from about 1,100 to
about 14,000. Also sutiable are the polyoxyalkylene derivatives
of ethylene diamine, e.g., the materials sold under the trademark
TETRONIC.
Suitable non-ionic surfactants for use as the hydro-
philic, non-aqueous vehicle in the tooth paste or gel composition
of the invention include materials such as polyoxyethylene sorbi-
tan fatty acid esters, e.g., materials sold under the trademark
TWEEN. Examples of such materials are polyoxyethylene (20)
sorbitan monolaurate (TWEEN 20), polyoxyethylene (20) sorbitan
monopalmitate (TWEEN 40), polyoxyethylene (20) sorbitan mono-
stearate (TWEEN 60), polyoxyethylene (4) sorbitan monostearate
(TWEEN 61), polyoxyethylene (20) sorbitan tristerate tTWEEN 65),
.
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polyoxyethylene (20) sorbitan monooleate (TWEEN 80), polyoxyethy-
lene (5) Sorbitan monooleate (TWEE~l 81), and polyoxyethylene (2Q)
sorbitan trioieate (TWEEN 85).
Polyoxyethylene fatty acid esters are also suitable for
use as the vehicle in the tooth paste composition of the inven-
tion. Examples include those materials sold under the trademark
MYRJ such as polyoxyethylene (8) stearate (MYRJ 45) and polyoxy-
ethylene (40) stearate (MYRJ 52).
Another suitable class oE non-ionic surfactants for use
in the vehicle in the present invention are polyoxyethylene fatty
ethers, e.g., the materials sold under the trademark BRIJ. Exam-
ples of such materials are polyoxyethylene (4) lauryl ether (BRIJ
30), polyoxyethylene (23) lauryl ether (BRIJ 35), polyoxyethylene
(2) cetyl ether tBRIJ 52), polyoxyethylene tlO) cetyl ether (BRIJ
56), polyoxyethylene (20) cetyl ether (BRIJ 58), polyoxyethylene
(2) stearyl ether (BRIJ 72), polyoxyethylene (10) stearyl ether
(BRIJ 76), polyoxyethylene (20) stearyl ether (BRIJ 78), poly-
oxyethylne (2) oleyl ether (BRIJ 93), polyoxyethylene (10) oleyl
ether, and polyoxyethylene (20) oleyl ether (BRIJ 99).
In one embodiment of the invention, a portion of a non-
ionic surfactant employed in the vehicle in the composition of
the invention can be substituted with a lipophilic surfactant,
e.g., sorbitan fatty acid esters such as the materials sold under
the trademark ARLACEL. Suitable lipophilic surfactants include
,
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sorbitan monolaurate (ARLACEL 20), sorbitan monopalmitate
(ARLACEL 40), sorbitan mGnostearate (ARLACEL 60), sorbitan mono-
oleate (ARL~CEL 80), sorbitan sesquioleate (ARLACEL 83), and sor-
bitan trioleate (ARLACEL 85). Typically, from about 10 to about
90% of the non-ionic surfactant can be substituted by a lipo-
philic surfactant, preferably from about 25 to about 50~.
As noted above, other classes of surfactants such as
cationic surfactants, anionic surfactants, ampholytic surfactants
and alkanolamides can also be employed as the vehicle in the com-
position of the present invention. Such materials can beemployed either by themselves as the vehicle or together with a
polyakylene glycol or a non-ionic vehicle as discussed above.
Examples of suitable anionic, cationic, ampholytic and alkamo-
lamide surfactants include di-tallow dimethyl ammonium chloride,
sodium lauryl sulfate, the material
CON-CH2
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OH / CH2CH2ONa
CH2COONa
sold under the trademark MIRANOL, and coconut alkanolamide.
Typically, when these materials are used as part of the vehicle,
they are substituted for from about 10 to about 90% by weight,
preferably from about 25 to about 50~ by weight, of the main
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vehicle used in the composition, e.g., a polyalkalene glycol or a
non-ionic surfactant as discussed above.
Auxiliary stabilizers can also be included in the com-
positions of the invention in order to augment stabilization of
the bicarbonate, and especially of the peroxide component. These
can comprise dessicating agents to absorb trace water, or can
comprise chemical stabilizers.
Any orally acceptable material that stabilizes the
peroxide during storage of the composition in a closed container
can e.g. be employed as an auxiliary stabilizer in the present
composition. Examples of suitable such stabilizing agents
include desicating agents, sequestering agents, colloidal parti-
cles, free radical preventatives, inorganic hardness salts, acid-
ulating agents, and mixtures of such stabilizing agents.
Examples of suitable dessicating agents include magne-
sium sulfate, sodium sulfate, calcium sulfate, calcium chloride
and colloidal silica, e.g., colloidal silica particles sintered
together in chainlike formations having surface areas of from
about 50 to about 400 square meters per gram such as materials
sold under the trademark Cab-O-Sil0 by Cabot Corp. It is
believed that such materials act to stabilize the compositions of
the invention by, for example, absorbing any existing water
either present in or contacted with the composition so as to fur-
ther preclude breakdown of the peroxide and/or bicarbonate.
12~36~394
-23-
Colloidal pyrogenic silica serves a further purpose in
the present compositions, i.e. it is a well-recognized thickener,
and is very useful in achieving a desired consistency for both
practical and aesthetic reasons.
- 5 Examples of suitable sequestering and/or chelating
agents include ethylene diamine tetraacetic acid (EDTA) or its
sodium salts, nitrilotriacetic acid or its sodium salts, diethy-
lene triamine pentaacetic acid (DTPA), or DEQUEST phosphonates
available from Monsanto. It is believed that such chelating or
sequestering agents stabilize the compositions of the invention,
for example, by tying up metal ions such as Fe+3, Mn+2, Cu+2,
etc. that can catalyze the decomposition of peroxide in the com-
positions.
other effective auxiliary stabilizers for use in the
present composition include in addition to the colloidal parti-
cles such as the pyrogenic silica mentioned above, finely divided
clays, zeolites and insoluble metallic oxides, e.g., magnesium
and aluminum oxide. The pyrogenic silica materials are a pre-
ferred auxiliary stabilizing agent in the compositions of the
present invention.
Also, free radical inhibitors or preventatives such as
butyl hydroxytoluene, butyl hydroxyanisole and beta carotene can
also reduce the instability of peroxide in the composition of the
invention.
:,,
:
12~69~4
-24-
Inorganic hardness salts such as calcium or magnesium
inorganic compounds also reduce peroxide instability. Examples
of such compounds include magnesium carbonate, magnesium chlo-
ride, calcium sulfate, calcium chloride and the like.
The addition of anhydrous acidulating agents or their
salts tpowdered or granulated), also provide improvement in
peroxide stability in the compositions of the invention. Exam-
ples of suitable acidulating agents for use in the present inven-
tion include ascorbic acid, tartaric acid, phosphoric acid as
well as the chloride, sulfate or nitrate salts of calcium, mag-
nesium or ammonium.
- The inclusion of an auxiliary stabilizing agent in the
composition of the present invention has been found to provide
- increased stability of the compositions in comparison to composi-
tions without such stabilizing agent. For example, when 5% by
weight of pyrogenic colloidal silica (Cab-o sil M-5) was
employed in combination with 10% by weight baking soda and lO~ by
weight urea peroxide in a polyethylene glycol 600 vehicle
(remainder), a 96~ residual peroxide level was found after stor-
age of the composition in a closed container for 18 days at room
temperature. By contrast, with a similar composition omitting
~- the pyrogenic colloidal silica, only a 90% residual peroxide
level was obtained under the same conditions. Typically, the
auxiliary stabilizing material is included in the compositions of
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699~
-25-
the present invention in an amount of from 0.1 to about 7.5%,
preferably from about 1 to about 5~ For exa~ple, when pyrogenic
colloidal silica materials are used as an auxiliary stabilizing
agent (and thickener~, suitable amounts thereof are from 1 to
about 7.5% by weight, preferably from about 3 to about 5% by
weight.
One embodiment of the invention and composition also
includes chloride and/or sulfate salts such as alkali metal chlo-
rides or sulfates, alkaline earth metal chlorides or sulfates, or
0 mixtures thereof. Suitable chloride salts for use in the compo~
sition of the invention include sodium chloride, potassium chlo-
ride, lithium chloride, calcium chloride, magnesium chloride,
sodium sulfate, potassium sulfate, magnesium sulfate, etc.
Typically, the chloride salts or other salts are
included in the composition of the present invention in amounts
of from about 1 to about 50% by wsight of ths composition. Pre-
ferably, the chlorids or other salts ars includsd in an amount of
from about 1 to about 15~ by wsight of ths composition.
The compositions of ths invention can include many
other componsnts which are conventional in the art, again depend-
ing upon the ultimate use to be made of the composition. As with
all the componsnts of the composition, these components should
prsfsrably be of the class generally recognized as safe, espe-
cially for use in the mouth. For example, the composition of the
. . .
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99~
-26-
invention can include conventional adjuvants, e.g., colorants,
flavors, sanitizing agents, dentally acceptable abrasives,
cleansing agents, and the like.
The compositions of the present invention can be pre-
pared by methodology conven~ional in the art. For example, theperoxide material (either coated or encapsulated, sorbed on a
solid material or a solid material itself) can be physically
mixed with the (preferably) coated bicarbonate salt, and any
other materials to be included in the compositions of the inven-
tion, such as a chloride salt or other carriers and/or adjuvants.The composition can be prepared into a paste or gel again in a
manner conventional for preparing such paste or gels as is well-
known in the art by merely including the desired amount of the
peroxide, auxiliary stabilizer (if used) and bicarbonate in the
desired hydrophilic, non-aqueous vehicle. As noted above, the
paste or gel is non-aqueous.
In a preferred method of preparing a composition of the
present invention, an auxiliary stabilizer and thickener such as
a pyrogenic colloidal silica material, is first mixed with the
hydrophlic, non-aqueous vehicle, such as polyalkylene glycol,
~ e.g. of polyethylene glycols such as Carbowax~ 400 and Carbowax~
8,000. Additonal surfactants can also be present to provide good
foaming when used in the mouth. To such mixture is added the
peroxide, such as urea peroxide with stirring. The peroxide can
- - . : . . :
~LZ~3~99~
-27-
as noted above, be optionally coated with the barrier coating.
The bicarbonate salt is then added to the mixture containing the
peroxide. The bicarbonate salt can likewise be (and preferably
is) pre-coated as discussed above. other desired adjuvants can
S be added at the tail end of this process, some of which adjuvants
may be provided with a water soluble barrier coating as already
indicated.
The dentifrice adjuvants (foaming agent(s), flavor(s),
colorant(s), dentifrice abrasive(s), fluorine-containing com-
pound(s) etc.) may likewise be provided with a water-soluble
coating, either by treating same alone or in combination, or by
treatment together with the peroxide and/or with the bicarbonate.
The coated dentifrice adjuvants may be incorporated in the vehi-
cle when not co~bined with the peroxide or bicarbonate.
The compositions of the present invention as noted
above can be used to treat periodontal disease. In such treat-
ment, it is believed that the composition of the invention
attacks the anerobic bacteria that cause such periodontal
disease. In the method of the present invention, the composi-
tions described above are applied to the gums of the patient,
e.g., a mammal such as man, in an amount effective to inhibit the
bacterial motility of the oral anerobic bacteria and other bacte-
rial types.
The invention is further illustrated by the following
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~l2~3~i994
-28-
Examples, which are, however, intended to be illustrative, and
not delimitive of the invention which is otherwise set forth:
Example I
A composition in accordance with the present invention
is prepared in the form of a paste or gel. A high molecular
weight polyethylene glycol, Carbowax~ 8,000, is warmed and com-
bined with a low molecular weight polyethylene glycol, Carbowax~
400. This mixture is stirred and Cab-o-sil~ M-5 is added thereto
and mixed therewith. Baking soda pre-coated with 10% of an edi-
- ~ ..... i .- .
ble non-toxic water soluble starch is used in this formulation.
Urea peroxide is added to the polyethylene glycol/Cab-o-sil~ mix-
ture and stirred. Then the coated baking soda is added with
stirring. Suitable flavoring agents and a foaming agent,
~APROFIX 563, is added to and mixed with the resultlng mixture.
The mentioned surfactant is a purified oral grade of sodium
lauryl sulfate. The weight percent of the respective ingredients
in the COmpOSitlOn of this Example are listed below:
- : ....... : . . .: ~ :-
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9g~
Ingredient ~ by Weight
Polyethylene glycol 8,000
(Carbowax~ 8,000) 14.9
Polyethylene glycol 400
(CarbowaxX 400) 75.4
Pyrogenic colloidal silica
(Cab-o-Sil M-5) 1.8
Urea Peroxide (Rebecco) 3.5
Coated Baking Soda
(Durkee MC-90 -- lO~ coating by weight 3.9
- Flavoring agents 0.5
Surfactant - sodium lauryl sulfate
(Maprofix 563 - ~nyx-Chemical Co. 0.5
This toothpaste (or "gel") is a cosmetically acceptable
dentifrice which produces bactericidally active oxygen in use.
The composition is "package stable" (as generalIy recognized)
under reasonable conditions of storage when packaged in a squeeze
tube or pump-type of container; i.e. the formation of gases
(C2 and 2) that would otherwise occur in a single phase unsta-
bilized composition of peroxide and bicarbonate is effectivelyinhibited. Typical test procedures for confirming such package
stability involves subjecting the composition in a closed con-
tainer to 3 weeks storage at 105C.
- - Example II
In this Example, a further paste or gel similar to that
of Example I is prepared, wherein the respective ingredients are
as fol}ows:
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~l2~994
-30-
Ingredient % by Weight
Polyethylgne glycol 8,000
tCarbowax 8,000t 11.0
Polyethylene glycol 400
(Carbowax~ 4nO) 76.24
Pyrogenic colloidal silica
(Cab-o-Sil M-5) 3.5
Urea P~roxide (Rebecco)
with 10% coating by weight 3.9
Baking Soda (Church & Dwight)
Grade 5, with 10% coating by weight 3.9
Flavoring agents 1.9
Surfactant foaming agent - sodium
lauryl sulfate 0.56
15Both the urea peroxide and the baking soda are provided
- with a coating of 10% by weight of maltodextrin (Lodex 10 product
of Durkee Foods) by being sprayed with an aqueous solution of the -
said product as the particulate peroxide and baking soda are
maintained in a fluidized bed. The final composition is again a
package stable, cosmetically acceptable dentifrice which produces
bactericidally active oxygen in use.
The flavoring agents can include known dentifrice adju-
vants, such as methyl salicilate, menthol, sodium sacharin (or
other sweeteners, e.g. Nutrisweet~), and colorants. Also, con-
ventional dentifrice abrasives and fluorine-containing compounds
can be provided.
~L2~36~39~
Example III
A dentifrice paste or gel similar to that of Example II
is prepared, except that the foaming agent (sodium lauryl sulfate)
is also provided with a 10% coating of maltodextrin, which tends
to further augment stability in the final product. The method of
coating is as aforementioned, i.e. by spraying the coating onto
the powdered agent while same is suspended in a fluidized bed.
The resulting dentifrice has characteristics as in Example II.
The foaming agent can typically be present from about 0.1% to
- 10 about 10.0%, with the proportion of the vehicle being suitably
adjusted.
Example IV
A dentifrice paste or gel similar to that of Example
III is prepared, except that 10% dicalcium phosphate is added
as a dental abrasive, (more generally 1-50% of an abrasive can be
used, with 1-15% being preferable), with the weight percent in
the total composition of the vehicle (i.e. glycol 8,000 and
glycol 400) being adjusted accordingly. The dicalcium phosphate
is coated in advance with 10% maltodextrin, as described for the
foaming agent in Example III, in order to maintain and augment
stability in the final product. The resulting dentifrice has
characteristics, including stability, as in Examples II and III.
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36994
Example V
A dentifrice paste or gel similar to Example IV is pre-
pared, except that the dentifrice "adjuvant package" is as fol-
1 ows:
Ingredient% by weight of total composition
foaming agent-sodium -
lauryl sulfate l.0
dental abrasive-dicalcium
phosphate lO.0 ~
Flavor mix 3.0 -.
- ~ - Sweetener~sodium sacharine 0.3
The adjuvants are provided with a 10~ by weight barrier
coating as in Example IV. The vehicle proportion is adjusted to
provide a 100% total. The resulting dentifrice has characteris-
tics including stability, as in Example IV.
: :
Example VI
: A dentifrice paste or gel similar to that of Example II
is prepared except that the barrier coating is provided by spray-
~:~ ing the actives to provide a 10% by weight coat of Methocel~,
e.g. Methocel E-4M. :The resulting dentifrice has stability as in
:: : '
Examples II and III.
~ '': '
; Example VII
: Dentifrice pastes or gels are prepared similar to Exam-
ple II, but wherein water soluble barrier coatings on the actives ~ :
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-33-
(urea peroxide and sodium bicarbonate) are provided by spraying
on 10% by weight coatings of the Capsul9, Starch 469, and N-LOK~
soluble starch products of National Starch. The resulting denti-
frices have stabilizers as in Examples II and III.
Example VIII
Dentifrice pastes or gels are prepared similar to Exam-
ple II, except that water soluble barrier coatings on the actives
(urea peroxide and sodium bicarbonate) are provided by spraying
- on 10~ by weight coatings of guar gum, sodium alginate and kelgi-
nate gum polymer from aqueous solutions of same. The finally
resulting dentifrices have stabilities as in Examples II and III.
The following Examples IX and X illustrate the advan-
tages of utilizing auxiliary stabilizers andjor alternate vehi-
cles. In each instance a toothpaste or gel composition was pre-
pared by mixing together the indicated auxiliary stabilizer withthe vehicle component(s). The peroxide and then the bicarbonate
salt are mixed in with the stabilizer vehicle mixture. The
actives and adjuvants in these Examples can be coated in accord-
; ance with the invention to provide greater stability.
Example IX
This composition is prepared in the form of a paste orgel. A polyethylene glycol 600 is warmed and combined with a
polyethylene glycol 400. This mixture is stirred and Cab-o-sil~
:,
- ., : '~ ' . ................... . :
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994
-34-
M-5 is added thereto and mixed therewith. Urea peroxide is added
to the polyethylene glycol/Cab-o-sil~ mixture and stirred. The
baking soda (Grade 5 from Church ancl Dwight) is added with stir-
ring. Suitable flavoring agents anc1 sodium chloride are added to
and mixed with tha resulting mixture. The weight percent of the
respective ingredients in the composition of the invention are
listed below.
Ingredient ~ by Weight
Polyethylene glycol 400
- 10 (Sentry Grade) 33
Polyethylene glycol 600
(Sentry Grade) 45%
Pyrogenic colloidal silica
(Cab-o-Sil M-5) 7.5~
Urea Peroxide 3.5%
Baking Soda (Grade 5
from Church and Dwight) 3.5
Flavoring agents, foaming agents,
and dental abrasive 6.5%
Sodium chloride 1.0%
~'
This toothpaste has a commercial consistency and chemi-
cal stability (determined by permanganimetric titration) that is
over 88~ stable with respect to peroxide at 105 for one month ~ -
and 29~ stable at 120F for one month. The conventional addition
of normal flavoring agents provides the paste with a conventional
tooth paste-like taste.
.
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36994
-35-
Example X
A series of toothpaste compositions is prepared by the
general procedure described in Example IV above employing the
ingredients listed below in the indicated proportions:
Ingredients ~ by Weight
NaHCO3 3-5
Urea Peroxide 3.5
Polyethylene glycol 400 (40%)
- - vehicle 88
Polyethylene glycol 600 ~60~)
Magnesium Sulfate 5
Anhydrous powder
'~'
Anhydrous sodium sulfate, calcium sulfate or calcium
chloride can be substituted for the magnesium sulfate in the
above formulation.
Ingredients ~ by Weight
NaHCO3 3,0
Urea Peroxide 3.1
Polyethylene glycol 400 (40~
vehicle 87.4
Polyethylene glycol 600 t60~) .
EDTA 2.0
Cab-o-sil M-5 4.5
' '' ~
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~2t36994
-36-
Nitrilotriacetic acid (or its salts), diethylene tri-
amine pentaacetic acid (or its salts), or Dequest phos~phate
chelating agents can be substituted for the ethylene diamine
tetracetic acid (EDTA) in the above formulation.
Ingredients ~ by Weight
Urea Peroxide 2.7
NaHC03 2.7
Cab-o-Sil M-5 4.0
Polyethylene glycol 400 (40%)~
` ^ 10 vehicle88.1
Polyethylene glycol 600 (60%)
Magnesiu~ oxide 2.5
Finely divided (colloidal) clays, zeolites and other ~ .
insoluble metallic oxides such as aluminum oxide can be substi-
15 tuted for magnesium oxide in the above formulation.
~ .
Ingredients ~ by Weight
Urea Peroxide 2.0
NaHC03 2.0
Cab-o-Sil~ M-5 3.0
Polyethylene glycol 400 (40~
vehicle92.0
Polyethylene glycol 600 (60~ . .
Butyl hydroxytoluene 1.0
,: '
~2~699~
-37-
Butyl hydroxyanisole or beta carotene can be substi-
tuted for the butyl hydroxytoluene in the above formulation.
Ingredients % by Weight
Urea Peroxide 3.1
NaHCO3 3.1
Cab-o-Sil~ M-5 4.5
Polyethylene glycol 400 (40%)
vehicle84.3
Polyethylene glycol 600 (60%)
Magnesium carbonate 5
Ingredients % by Weight
Urea Peroxide 2.5
NaHCO3 2.5
Cab-o-Sil M-5 4.2
Anhydrous Citric Acid 0.5
Polyethylene glycol 400 (40~)
vehicle 9l.3
Polyethylene glycol 600 (60~)
Absorbic acid, tartaric acid, phosphoric acid as well
: 20 as the chloride, sulfate, nitrate salts of calcium, magnesium and
ammonium may be substituted for the anhydrous citric acid in the
above formulation.
. . ~ - , :
~Z~6~94
-38-
Ingredients ~ by Weight
Urea Peroxide 3. 75
NaHCO3 3 . 75
Polyoxypropylene
S polyoxyethylene glycol 85
( PLURONIC L-72 )
Cab-o-sil~ M-5 7 . 5
PLURONIC-25R may be substituted for PLURONIC L-72 in
the above formulation.
Ingredients % by Weight
Urea Peroxide 3.0
NaHCO3 3.0
Polyoxyethylene ( 20)
sorbitan monooleate
(Tween 80) 88.0
Cab-o-sil M-5 6.0
Polyoxyethylene (2) steryl ether ( BRIJ 72 ) or polyoxy-
ethylene (8) sterate (MYRI 45) may be substituted for TWEEN 80 in
the above formulation. In addition, a portion of the TWEEN 80,
e.g., one-half, may be substituted with polyethylene glycol 600.
'' ~ ' ' ' ' ' . ,~ , ' :
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i994
-39
Ingredients% by Weight
Urea Peroxide 3.5
NaHCO3 3-5
Polyoxyethylene (20)
Sorbitan monooleate
(TWEEN 80) 60.0
Sorbitan Monooleate
(Arlacel 20) 26.0
Cab-o-sil~ M-5 7.0
Ingredients
Calcium Peroxide4.0
NaHCO3 4.0
Cab-o-sil~ M-5 7.0
Di-tallow dimethyl
ammonium chloride 10.0
~ Polyethylene glycol 600 75.0 :~
; An anionic surfactant such as sodium lauryl sulfate, an
ampholytic surfactant such as Miranol~/ or an alkanolamide such
~` as coconut alkanolamide may be substituted for the di-tallow
~ 20 dimethyl ammonium chlorlde in the above formulation.
:~ :
: Ingredients~ by Weight : -
Magnesium Peroxide 5.0
Potassium bicarbonate 3.0 -~.
PLURONIC L-72 84.5
Cab-o-sil~ M-5 7.5
-.
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12~36994
-40-
The above formulation can also be prepared by replacing
half of the PLURONIC L-72 with polyethylene glycol 400 or poly-
ethylene glycol 600.
The above formulations in this Example illustrate the
various auxiliary stabilizers and vehicles that can be used
either alone or in combination in the compositions of the present
invention.
While the present invention has been particularly set
forth in terms of specific embodiments thereof, it will be under-
stood in view of the instant disclosure, that numerous variationsupon the invention are now enabled to those skilled in the art,
which variations yet reside within the scope of the present
teaching. Accordingly, the invention is to be broadly construed,
and limited only by the scope and spirit of the claims now
appended hereto.
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